PMID- 7620375
TI  - Early sensitization to airborne allergens.
AB  - We report the case of a 7-month-old child with failure to thrive. Celiac disease
      was suspected because of highly raised antigliadin IgA and IgG antibodies and
      subtotal villous atrophy. In peripheral blood mononuclear-cells cellular
      proliferation was found in response to birch pollen, rye pollen and hazelnut
      extract. Born in June 1992 the infant had not yet experienced a birch pollen
      season. He had been fed with birch pollen allergy-associated carrot, apple and
      potato beginning at 6 weeks of life. In the serum, specific IgG, IgM and IgA to
      birch pollen and profilin, rye pollen and hazelnut antigens were detectable,
      indicating possible in utero sensitization or T cell cross-reactivity due to
      early sensitization with related food antigens.

PMID- 7620376
TI  - [Surgical treatment of breast carcinoma since Hippocrates of Cos].
AB  - The pessimistic prognosis for cancerous diseases made by the founder of
      occidental medical science, Hippocrates of Cos (ca. 460 BC--ca. 370 BC), resulted
      also in the fact that the surgical treatment of breast cancer was performed
      rather as a last resort. Not until the rise of scientific surgery in the 16th
      century did European surgeons begin to develop different procedures in the
      surgical treatment of breast cancer. In 1774, in a treatise rewarded by the
      Academy, the French surgeon Bernard Peyrilhe, who may be considered one of the
      founders of experimental cancer research, demanded radical operative surgery in
      cases of breast cancer. Peyrilhe first formulated the principles of that surgical
      concept which is connected with the name of the American surgeon William Stewart
      Halsted (1852-1922), a concept which has long remained influential.

PMID- 7620377
TI  - [Hysteroscopy--applications and risks. Hysteroscopy versus fractionated
      curettage: therapeutic insufficiency of abrasion].

PMID- 7620378
TI  - [Applications of hysteroscopy within the scope of modern gynecology].

PMID- 7620379
TI  - [Surgical standards in cervix carcinoma].

PMID- 7620380
TI  - [Surgical standards in endometrial carcinoma].

PMID- 7620381
TI  - [Surgical standards in ovarian carcinoma].

PMID- 7620382
TI  - [Surgical standards in breast carcinoma].

PMID- 7620383
TI  - [The language of science].

PMID- 7620384
TI  - [Indications for hysterectomy].
AB  - Large deviations, regional differences and the decline in hysterectomy
      frequencies suggest that the indication for hysterectomy has not always been
      based on well defined medical standards. Paramedical factors also have an
      influence on the indication. The patient has to decide in many cases whether she
      would like to tolerate the clinical symptoms, which could have been improved or
      healed by hysterectomy, or not. New endoscopic techniques as alternative to or
      support of the classical hysterectomy procedure have not yet been sufficiently
      proved. Influences on the costs of operations, the rate of complications and
      above all the setting of indications need further careful observation and
      analyses. It is difficult to establish quality assessment procedures in
      hysterectomy, because controlling the indication by histopathological examination
      of the exstirpated uterus cannot regard the variety of indications.

PMID- 7620385
TI  - [Hormonal replacement therapy and oral contraception. Risk of induction or
      reactivation of gynecologic malignancies].
AB  - The administration of oral contraceptives does not enhance the incidence of
      gynecologic malignancies. Only few subgroups of patients seem to have a slightly
      elevated relative risk of breast cancer. On the other hand, the incidence of
      endometrial and ovarian cancer is markedly reduced. This is also true for correct
      hormonal replacement therapy. In addition, no elevation of breast cancer risk has
      been evidenced for low-estrogen administration. In most cases, hormonal
      replacement therapy may also be performed safely following successful treatment
      of gynecologic cancers.

PMID- 7620386
TI  - [Local therapy and adjuvant interferon therapy in genital papilloma virus
      infections].
AB  - OBJECTIVE: Is it possible to reduce the recurrence rates of HPV-positive genital
      tract lesions by systemic interferon alfa-2a in addition to local therapy?
      METHODS: Thirty-three of 63 patients with first manifestation of papillomavirus
      infection or monolocal manifestation were treated by local therapy. The other 30
      patients with recurrent or multiorgan infections received 3 courses with 12 x
      10(6) IU interferon alfa-2a subcutaneously. RESULTS: For the remaining 47
      patients (16 were lost to follow-up) we found a significantly lower recurrence
      rate of 21% (5 of 24) in the group of interferon-treated patients compared to 52%
      (12 of 23) of patients treated without interferon. CONCLUSIONS: The systemic
      treatment of HPV-positive genital tract lesions with interferon alfa-2a in
      addition to CO2 laser surgery or cone biopsy seems to reduce the recurrence rates
      of HPV-positive lesions.

PMID- 7620387
TI  - [The synergistic effect of delta-aminolevulinic acid and photodynamic laser
      therapy based on an in vitro model of the ATP tumor chemosensitivity test].
AB  - Photodynamic laser therapy (PDT) is under prospective clinical evaluation in
      gynecology. We used the ATP tumorchemosensitivity assay to detect the efficacy of
      delta-aminolevulinic acid (ALA) in combination with PDT. Two invasive cervical
      cancer cell lines were used, C33 and SIHA. The cell-damaging effect was
      quantified by measuring the intracellular ATP content. The 50% inhibitory
      concentration of ALA was 760 microM in the cell line C33 and 500 microM in the
      cell line SIHA. The combination of ALA incubation and PDT was synergistic in both
      cell lines. After in vitro experiments with this method, the combination is now
      used in a clinical phase II study. PDT after topical ALA application promises to
      become a possible alternative for the treatment of preinvasive and invasive
      malignancies in gynecology.

PMID- 7620388
TI  - [Use of photodynamic laser therapy in gynecology].
AB  - OBJECTIVE: Dysplasia of the vulva and uterine cervix are often multicentric, tend
      to recur and have mostly to be treated by surgical procedures. The photodynamic
      laser therapy (PDT) may be an alternative, which selectively destroys neoplastic
      tissue after topical delta-aminolevulinic acid (ALA) used as a photosensitizer.
      METHODS: We measured the distribution of fluorescence in dysplastic and
      nondysplastic tissue after topical application of ALA in 27 patients with
      dysplasia. In 3 vulvar and 2 cervical dysplasias, PDT was performed. RESULTS: We
      could show a selective enrichment of endogenous porphyrins in dysplastic tissues,
      whereas benign tissue showed no fluorescence. The fluorescence was limited to the
      mucosa. The heterogeneous fluorescence pattern was influenced by the duration of
      ALA application. In the treated patients, cytological and clinical parameters
      showed improvement after use of PDT. The longest recurrence-free interval from
      treatment up to date is 15 months (range 3-15 months). CONCLUSIONS: After first
      results of penetration studies and clinical follow-up, PDT after topical ALA
      application seems to be a good alternative to surgical procedures in dysplastic
      changes of the genital tract.

PMID- 7620389
TI  - [Sarcoidosis. Case report of a patient with isolated sarcoidosis of the breast].
AB  - The case of a 41-year-old woman with sarcoidosis of the breast without evidence
      of disease elsewhere is reported. The diagnosis was established histologically,
      and other causes of the sarcoid-like granulomatous lesions could be excluded.

PMID- 7620391
TI  - Violence in health care: a strategic approach.
AB  - This article describes the problems of violence in the health care workplace.
      Methods are presented that can be used to analyze the factors that contribute to
      assaults on staff, to assess the type of violent event, and to develop prevention
      strategies.

PMID- 7620390
TI  - Cumulative trauma disorder: a primary care provider's guide to upper extremity
      diagnosis and treatment.
AB  - This article gives an overview of the nonmedical aspects of cumulative trauma
      disorder (CTD) such as workers' compensation and hazard evaluation. The
      pathophysiology and presenting symptoms of CTDs are addressed, including
      entrapment neuropathies of the median, ulnar, and radial nerves; thoracic outlet
      syndrome; and tendinitis of the elbow, shoulder, wrist, and thumb. History and
      specific examination techniques are discussed. There is a focus on primary care
      treatment options, which includes ergonomic interventions.

PMID- 7620392
TI  - How low can you go?

PMID- 7620393
TI  - Fran Devlin: nurse practitioner in occupational health. Interview by Karna
      Bramble.

PMID- 7620394
TI  - Overview of Norplant litigation.

PMID- 7620395
TI  - The retinoids, Part II.

PMID- 7620396
TI  - The occupational and environmental health history: guidelines for the primary
      care nurse practitioner.
AB  - The occupational and environmental health histories are often a neglected part of
      the patient evaluation in the primary care setting. Nurse practitioners (NPs) are
      in an important position to elicit information related to exposures that can
      affect patient health. This article offers data on basic concepts related to
      occupational and environmental medicine, and advises NPs on various approaches to
      obtaining an exposure history.

PMID- 7620397
TI  - Control of occupational and environmental hazards.
AB  - This article provides an overview of the control of occupational and
      environmental exposures. Two case studies illustrate common questions that arise
      in the primary care setting, regardless of specialty practice. The focus of these
      case studies is to offer pragmatic recommendations on how best to prevent
      occupational and environmental illness and injury through use of a hierarchy of
      controls.

PMID- 7620398
TI  - Temporary work restrictions: guidelines for the primary care provider.

PMID- 7620399
TI  - Pesticide exposure seen in primary care.
AB  - The focus of this article is on recognition of signs and symptoms of pesticide
      exposure and poisoning in primary care settings. Providers have little problem
      evaluating clients with an acute exposure to pesticides because the client
      usually presents with symptoms of poisoning and/or a history of known exposure.
      The information presented supports the need to consider a history of pesticide
      exposure in the evaluation of some neurological, dermatologic, reproductive, and
      other signs and symptoms presented to primary care providers.

PMID- 7620400
TI  - Reproductive hazards facing female health care workers in the hospital: how the
      nurse practitioner can help.
AB  - Female health care workers are often exposed to occupational hazards that may
      adversely affect their reproductive health and the health of their children. This
      article presents an overview of the problem and, through a case study, focuses on
      a small sample of agents (aerosol antimicrobials, disinfectants, and infectious
      diseases) that represent common hospital exposures with reproductive
      implications. The nurse practitioner's role in identifying and counseling
      patients who may have exposures to reproductive hazards is discussed.

PMID- 7620401
TI  - 1995 Undersea and Hyperbaric Medical Society annual scientific meeting. Palm
      Beach, Florida, 20-24 June 1995. Abstracts.

PMID- 7620402
TI  - Arteriohepatic dysplasia (Alagille's syndrome): unusual hepatic architecture and
      function.
AB  - BACKGROUND: Alagille's syndrome, also called arteriohepatic dysplasia, is a
      congenital anomaly consisting of hepatic, ocular, skeletal, and cardiac
      anomalies. The abdominal imaging findings were reviewed in eight patients with
      biopsy-proven Alagille's syndrome. One patient also had coexistent hepatocellular
      carcinoma. METHODS: Seven right upper quadrant sonograms, six hepatic CT studies,
      five hepatobiliary imaging studies, two hepatic MRI examinations, and two sulphur
      colloid liver spleen radionuclide studies were reviewed. RESULTS: The most
      striking abnormality was gross distortion of hepatic architecture. Five patients
      (63%) had marked external hepatic contour abnormalities, usually with either the
      entire liver or lobe having a predominately spherical shape. The portal vein was
      displaced by the spherical parenchymal component in four cases. Three other
      patients demonstrated marked hepatomegaly with no external contour abnormality.
      Hepatobiliary imaging studies demonstrated markedly prolonged excretion of the
      radiopharmaceutical in three of four patients examined. CONCLUSIONS: A diagnosis
      of Alagile's syndrome is suggested when a large, deformed and somewhat spherical
      liver is encountered, especially when hepatobiliary imaging studies demonstrate
      delayed excretion of radiopharmaceutical.

PMID- 7620403
TI  - Portal blood flow in the presence or absence of diffuse liver disease:
      measurement by phase contrast MR imaging.
AB  - BACKGROUND: In patients with diffuse liver disease, the portal flow dynamics
      change markedly in accordance with disease progression and would provide a useful
      index of progression of stage. METHODS: Portal blood flow (PBF) was measured by
      phase contrast magnetic resonance imaging (MRI) in 21 patients with diffuse liver
      disease and 20 healthy volunteers. The MRI method was validated by a flow phantom
      study. The mean PBF could be measured in 6.8 min without breath-holding. RESULTS:
      Doppler ultrasound measurements of PBF volume were obtained reproducibly in all
      the healthy volunteers and were shown to correlate with the MRI values (Doppler:
      12.5 +/- 3.2 cm3/s, MRI: 12.0 +/- 3.3 cm3/s; mean +/- SD). The PBF volume of
      patients with chronic hepatitis showed no significant difference from that of the
      healthy volunteers. In patients with liver cirrhosis, the PBF volume ranged from
      5.01 to 32.3 cm3/s. A significant increase in PBF volume was caused in one
      patient by massive intrahepatic shunting and a significant decrease was caused in
      two patients by massive extrahepatic shunting. CONCLUSIONS: The measurement of
      PBF by phase contrast MRI is clinically useful in predicting intrahepatic or
      extrahepatic shunting in patients with liver cirrhosis, and may be of value in
      detecting the progression of stage in diffuse liver diseases.

PMID- 7620404
TI  - The association of paracardial adenopathy with hepatic metastasis found on CT
      arterial portography.
AB  - BACKGROUND: The association of paracardial lymphadenopathy with hepatic
      metastases in patients undergoing computed tomographic arterial portography
      (CTAP) prior to possible resection of hepatic metastases is documented. METHODS:
      CTAP was performed on 45 patients with hepatic metastasis, including 30 with
      colorectal carcinoma, using 1 cm increments from the dome of the diaphragm
      through the liver. Two radiologists, blinded to the diagnosis and surgical
      results, reviewed all portograms and identified all paracardial lymph nodes
      larger than 8 cm. RESULTS: Enlarged paracardial lymph nodes were found in three
      of the 30 colorectal carcinoma patients and two of the remaining 15 patients. All
      three colorectal patients with paracardial lymphadenopathy demonstrated massive
      metastatic involvement of the anterior segment of the right hepatic lobe (segment
      8: Couinaud nomenclature). Additional metastasis in the superior aspect of the
      liver was seen in two of these patients as well. Both patients without colorectal
      carcinoma with paracardial lymphadenopathy had metastasis involving the superior
      aspect of the liver. Paracardial lymphadenopathy was right-sided in all five
      patients and bilateral in one. By contrast, 48% (19 of 40) of patients without
      enlarged paracardial lymph nodes had metastasis in the anterior segment of the
      right lobe. CONCLUSIONS: This study suggests that paracardial lymphadenopathy is
      associated with metastatic disease to specific areas within the liver. This nodal
      involvement can be attributed to lymphatic drainage from the diaphragmatic
      surface of the liver.

PMID- 7620406
TI  - Liver volume assessment by conventional vs. helical CT.
AB  - BACKGROUND: Accurate noninvasive measurement of the volume of the liver has many
      potential clinical applications and is an important element in the preoperative
      evaluation of the liver transplant recipient. Helical (or spiral) computed
      tomography (CT) has theoretical advantages over conventional CT in this
      application because the entire liver can be imaged in a single breath-hold,
      limiting inaccuracies related to patient motion and respiratory variation.
      METHODS: We compared liver volumes measured by conventional CT and helical CT in
      22 patients undergoing preoperative evaluation for liver transplantation.
      RESULTS: The mean volume for helical CT is 1328 ml (SD 405) and conventional CT
      is 1323 ml (SD 417). CONCLUSIONS: We found no significant difference between the
      helical CT and conventional CT volumes for each patient.

PMID- 7620405
TI  - Percutaneous biopsy of liver tumors with color Doppler US guidance.
AB  - BACKGROUND: Percutaneous liver biopsy is a well-established procedure. Aim of
      this study was to investigate the usefulness of color Doppler ultrasound (US) for
      guiding percutaneous biopsy of liver tumors in patients at high risk of bleeding.
      METHODS: Forty-seven patients with severe, uncorrectable coagulopathy (platelet
      count < 50 x 10(9)/L and/or prothrombin time ratio [normal/patient] < 50%) were
      submitted to percutaneous biopsy of focal liver lesions using a 21 G cutting
      needle. The procedure was guided by color Doppler US, avoiding the needle cross
      into any liver or tumor vessel. RESULTS: Biopsy material was adequate for
      pathological reading in 46/47 cases (97.9%). No major post-biopsy complication
      was observed. In particular, no case of hemoperitoneum was detected on US
      examinations performed 2 hours after biopsy. Minor complications (including one
      subcapsular hematoma) occurred in 4 patients (8.5%). CONCLUSIONS: Color Doppler
      US can safely guide percutaneous liver biopsy in patients at high-risk of
      bleeding.

PMID- 7620407
TI  - MRI differential diagnosis of intrahepatic biloma from subacute hematoma.
AB  - The magnetic resonance imaging (MRI) differential diagnosis of intrahepatic
      biloma from intrahepatic subacute hematoma has been reported in two cases. The
      biloma was heterogenously intense on T1-weighted images and homogenously
      hyperintense on T2-weighted images. The hematoma was hyperintense on the both T1-
      and T2-weighted MR images. The clinical significance of this MRI difference is
      that intrahepatic biloma needs drainage, whereas intrahepatic hematoma can heal
      spontaneously.

PMID- 7620408
TI  - Amebic abscess of the liver manifested by "hemoptysis": US, CT, and MRI findings.
AB  - Ultrasonographic (US), computed tomographic (CT), and magnetic resonance imaging
      (MRI) findings of a patient suffering from an amebic abscess of the liver
      complicated by a bronchohepatic fistula are presented. Subsequent to US, CT
      provided the specific diagnosis. Multiplanar MRI was valuable to directly
      visualize the secondary diaphragmatic rupture and the bronchohepatic fistula.

PMID- 7620409
TI  - Abscess formation as a late complication of dropped gallstones.
AB  - We describe a case of abscess formation 1.5 years postoperatively in a patient
      with dropped gallstones from laparoscopic cholecystectomy. The entity was
      initially recognized on computed tomography (CT) and the diagnosis was confirmed
      with ultrasound. Although this is a rare complication of laparoscopic
      cholecystectomy, it should be recognized as a potential source of abscess
      formation even in a patient presenting months after the procedure.

PMID- 7620410
TI  - Delayed peritoneal and retroperitoneal abscesses caused by spilled gallstones: a
      complication following laparoscopic cholecystectomy.
AB  - Many complications following laparoscopic cholecystectomy have been reported. We
      report a case of delayed peritoneal and retroperitoneal abscesses caused by
      spilled gallstones from a laparoscopic cholecystectomy performed 1 year earlier.
      This diagnosis was suggested only at sonography because the aggressive behavior
      of the lesions containing nonopaque gallstones suggested, by computed-tomography
      scan, peritoneal metastatic disease.

PMID- 7620411
TI  - Endoscopic ultrasonographic-guided punctured pancreatic ductography: an initial
      and successful trial.
AB  - A 71-year-old male suffering from an intraductal papillary tumor of the pancreas
      was admitted to our hospital for further investigation. Diagnostic trials,
      including endoscopic retrograde pancreatography, did not produce an adequate
      ductography because of a large amount of mucinous fluid. Therefore, we performed
      endoscopic ultrasonographic-guided punctured pancreatic ductography (EPPD). This
      procedure was safely performed without any complications. We report this initial
      and successful trial of EPPD.

PMID- 7620412
TI  - Premature contraction of the cricopharyngeus: a new sign of gastroesophageal
      reflux disease.
AB  - BACKGROUND: A cricopharyngeal bar seen on barium fluoroscopy has been shown to be
      related to the presence of gastroesophageal reflux (GER). We investigated
      premature contraction of the cricopharyngeus (PCC) muscle, which may be a
      precursor of a fixed cricopharyngeal bar, to assess its significance in GER.
      METHODS: The prevalence of PCC on barium swallow was recorded in three groups:
      (1) 83 patients with non-cardiac chest pain who were investigated for possible
      GER; (2) 21 patients with severe GER undergoing fundoplication; and (3) 25 normal
      controls. RESULTS: Group 1: PCC was observed in 42 of 77 with documented GER
      (54.5%), and in two of six patients without GER. Group 2: PCC was present in 11
      of 21 fundoplication subjects. Group 3: PCC was seen in five of 25 normal
      controls. The incidence of PCC in patients with GER was statistically
      significantly higher than in normal subjects (p = 0.002). The sensitivity of the
      presence of PCC as a predictor of GER is only 0.54, but the specificity is 0.774,
      with a positive predictive value of 0.883. CONCLUSION: We conclude that observing
      premature cricopharyngeal contraction during the first swallows of an upper
      gastrointestinal (GI) study should direct attention to the possibility of GER.

PMID- 7620413
TI  - Solid-state computerized manometry improves diagnostic yield in pharyngeal
      dysphagia: simultaneous videoradiography and manometry in dysphagia patients with
      normal barium swallows.
AB  - OBJECTIVE: Dynamic barium radiology with cine- or video recording has been the
      most frequently used technique for assessing patients with pharyngeal dysphagia.
      Although the diagnostic yield of the barium swallow has been high, many patients
      with pharyngeal dysphagia have normal dynamic barium radiology and remain a
      diagnostic dilemma. Could manometry add important diagnostic information in these
      patients? MATERIAL AND METHODS: We examined 19 patients (12 men and 7 women, mean
      age 47 years, range 19-69 years) with pharyngeal dysphagia but a normal barium
      swallow with simultaneous videoradiography and pharyngeal manometry and compared
      their manometry to that found in 24 normal volunteers (11 men and 13 women, mean
      age 37 years, range 23-59 years). RESULTS: Comparing mean values, the patient
      group showed statistically significant differences from the control group for
      eight of 10 manometric parameters. Fourteen of 19 patients showed at least one
      (five patients) and in most cases multiple (nine patients) manometric
      abnormalities (values exceeding normal mean by +/- 2SD) which might have
      contributed to their dysphagia: five patients with high upper esophageal
      sphincter (UES) resting pressures, five with high UES residual pressures, three
      with weak pharyngeal contractions, three with pharyngeal "spasms," seven with
      prolonged contraction/relaxation times, five with reduced compliance, and seven
      with UES/P incoordination. CONCLUSIONS: Solid-state computerized manometry is a
      useful adjunct to videoradiography and can provide potentially important
      additional information in the diagnosis of dysphagia patients.

PMID- 7620414
TI  - Inverted Meckel's diverticulum simulating a pedunculated small bowel polyp.
AB  - We report a rare case of an isolated inverted Meckel's diverticulum presenting
      with acute gastrointestinal hemorrhage. The radiographic appearances simulated a
      pedunculated small bowel polyp. The radiographic and pathologic features are
      described and a brief review of the reported cases is provided.

PMID- 7620415
TI  - A combined flexible sigmoidoscopy and double-contrast barium enema service:
      initial experience.
AB  - BACKGROUND: A service has been instituted offering a combined single-stage
      procedure of flexible sigmoidoscopy and double-contrast barium enema (FS/DCBE).
      The results have been reviewed in the first 80 patients to undergo this
      examination (45 male: 35 female; mean age 61.4 years). METHODS: Indications for
      investigation were abdominal pain or suspected diverticular disease (22
      patients), altered bowel habit (19), rectal bleeding (17), iron deficiency anemia
      (6), and miscellaneous (16). FS was followed immediately by DCBE. Radiographs
      were reviewed by two radiologists unaware of the FS findings. RESULTS: The extent
      of FS was to the proximal sigmoid or sigmoid descending colon or splenic flexure
      in 12.5%, and mid or distal sigmoid in 37.5%. Biopsies were performed at FS in 26
      patients (33%). In 67 (84%) of DCBEs the barium coating was assessed as
      satisfactory or better. FS yielded pathological findings not seen at DCBE in 21
      patients (26%). DCBE demonstrated additional abnormalities within the range of
      the FS examination in 15 patients (19%), almost entirely due to its increased
      sensitivity for diverticular disease. CONCLUSION: FS/DCBE is feasible as a one
      stage combined procedure. The quality of DCBE following FS is satisfactory, and
      the extra yield of FS and its potential for biopsy make the combined FS/DCBE a
      useful technique in the investigation of large bowel disease.

PMID- 7620417
TI  - Digital subtraction in defecography.
AB  - BACKGROUND: Defecography is commonly used in investigation of pelvic floor and
      anorectal dysfunction, and incorporates measurement of pelvic floor movement
      during various maneuvers. These measurements are usually referenced to bony
      landmarks, particularly the ischial tuberosities. These bony landmarks may be
      difficult to visualize; theoretically, the use of digital subtraction in filming
      defecography studies should eliminate the need to pinpoint bony position.
      METHODS: We filmed 25 defecogram studies in both non-subtracted and subtracted
      formats, and interpreted each study blindly, subsequently comparing diagnoses and
      measurements. RESULTS: Subtraction was of limited benefit in only one case, was
      impossible in one case, added no useful information in 18 cases, and hindered
      visualization of abnormalities in five cases. CONCLUSIONS: Because of the
      multiple overlapping densities and the inability to restrict patient movement,
      digital subtraction is unhelpful in defecography.

PMID- 7620416
TI  - Imaging procedures in screening for colorectal cancer.

PMID- 7620418
TI  - MRI for evaluation of perianal inflammation.
AB  - BACKGROUND: We describe the value of using magnetic resonance imaging (MRI) in
      six distinct clinical settings often encountered in cases of perirectal
      inflammatory disease. METHODS: MRI was performed on six patients with known
      perianal inflammatory disease; the number, anatomic extent, location, and signal
      intensities of various lesions and their associated complications were assessed.
      RESULTS: MRI is a noninvasive technique that is useful in the diagnosis and
      management of perirectal inflammatory disease. CONCLUSIONS: In patients with
      known fistulas, MRI may determine the lesion's anatomic extent, localize
      unsuspected fistulas, and confirm or exclude the inflammation of the fistulous
      tract(s). Information obtained by MRI examination may, in turn, be used to
      determine treatment of patients with perirectal inflammatory lesions and can be a
      useful adjunct in following results of therapy.

PMID- 7620419
TI  - Transvaginal sonographic diagnosis of sigmoid diverticulitis.
AB  - The development of the transvaginal technique has allowed for high-resolution,
      detailed evaluation of the female pelvis. Although not previously emphasized, gut
      pathology can also be recognized with this technique. We report two cases of
      sigmoid diverticulitis which were prospectively diagnosed using endovaginal
      sonography. In both patients, pelvic sonogram was the first imaging study
      performed for evaluation of nonspecific abdominal pain.

PMID- 7620420
TI  - Tailgut cysts: CT and MR findings.
AB  - Two cases of tailgut cysts are reported. These lesions are rare and congenital,
      lying anterior to the sacrum and posterior to the rectum. CT findings are
      described. For one patient MR evidence is also presented. In a second case, the
      mass showed malignant behavior with local recurrence.

PMID- 7620421
TI  - Chylous cyst of the mesentery: US and CT diagnosis.
AB  - We report a case of mesenteric chylous cyst diagnosed preoperatively by
      ultrasonography (US) and computed tomography (CT). Both demonstrated a unilocular
      cystic mass with a fluid-fluid level. The CT number of the two components
      indicated fat density and water density and with shaking or positional changes,
      the contents displayed miscibility. The tumor changed its position during
      hospitalization. Both features are considered to be quite diagnostic of this
      condition.

PMID- 7620422
TI  - Implantation metastasis alongside an intraperitoneal chemotherapy catheter in
      ovarian carcinoma.
AB  - An elderly woman with recurrent ovarian malignancy was treated with
      intraperitoneal chemotherapy, administered via a subcutaneously buried catheter.
      She developed the unusual complication of a metastasis along the course of this
      catheter.

PMID- 7620423
TI  - Acute renal infarction caused by Behcet's disease.
AB  - A case of acute renal infarction due to Behcet's disease is described. Selective
      renal arteriography revealed multiple microaneurysms of both kidneys and arterial
      obstruction distal to an aneurysm in the left kidney. Bilateral microaneurysms
      were no longer seen on the follow-up angiogram 5 years later. Behcet's disease
      should be considered in the differential diagnosis of acute renal infarction in
      young adults.

PMID- 7620424
TI  - Bilateral perirenal urinoma with mediastinal extension.
AB  - We report a unique case of adult-type polycystic kidney disease (PKD) having
      bilateral chronic perirenal fluid collection with unusual extension. Fluid
      collections at both sides are connected across the midline anterior to the
      abdominal aorta and inferior vena cava. In addition, supradiaphragmatic extension
      through aortic hiatus was well demonstrated by computed tomography (CT).
      Antomical boundaries and relations between two perirenal spaces are evaluated.

PMID- 7620425
TI  - Focal xanthogranulomatous pyelonephritis simulating malignancy in children.
AB  - Xantogranulomatous pyelonephritis is a severe chronic form of renal parenquimal
      infection that usually results in diffuse renal destruction. An unusual case of
      xanthogranulomatous pyelonephritis in a child is reported which presented as a
      focal mass without calculus in a functioning kidney and was diagnosed as a renal
      tumor.

PMID- 7620426
TI  - CT and MR demonstration of fat within an adrenal cortical carcinoma.
AB  - Detection of fat within an adrenal primary mass is virtually pathognomonic of
      myelolipoma, and in most cases such a diagnosis excludes any further diagnostic
      and therapeutic approaches. We report our findings, with computed tomography (CT)
      and magnetic resonance (MR), of the first, to our knowledge, pathologically
      proven case of fat tissue within an adrenal cortical carcinoma. We also discuss
      the possible origin of fat within such malignancies and the potential diagnostic
      dilemmas it might cause.

PMID- 7620427
TI  - Characteristic morphologic changes in chronic ulcerative colitis.

PMID- 7620428
TI  - Vascular invasion by hepatocellular carcinoma.

PMID- 7620429
TI  - Re: The benefits or otherwise of evacuation proctography (defecography)

PMID- 7620430
TI  - Popcorn's predictions: a ten-trend guideline for planning your future.

PMID- 7620431
TI  - Tips for a successful ethics workshop.

PMID- 7620432
TI  - The shrinking staff development dollar: a problem no more.

PMID- 7620433
TI  - Ideas that work. A baker's dozen: selected strategies for successful precepting.

PMID- 7620434
TI  - Target your topics to catch up on your reading.

PMID- 7620436
TI  - Tips for writing behavior objectives.

PMID- 7620435
TI  - A model for management development.

PMID- 7620437
TI  - It matters which way you go: facilitating planning.

PMID- 7620438
TI  - Accreditation and credentialing. Competency validation: designing for success.

PMID- 7620439
TI  - Computers. Better data + critical thinking = improved care.

PMID- 7620441
TI  - Marathons, self-study, and birthday cake: CPR training.

PMID- 7620440
TI  - Using statistical packages to analyze effectiveness.

PMID- 7620442
TI  - Quality corner. Answers to redesign and multifunction worker questions.

PMID- 7620443
TI  - Delegation: the unteachable skill.

PMID- 7620444
TI  - Staffing. Collaboration: the way of the future in education.

PMID- 7620445
TI  - Use the inservice prep package to hurdle inservice obstacles.

PMID- 7620446
TI  - Mandatory nursing inservice: our hospital's creative approach.

PMID- 7620447
TI  - Five steps to gaining the attention, trust, and memory of learners.

PMID- 7620448
TI  - Orientation evaluation.

PMID- 7620449
TI  - Systems thinking: a pathway to organizational learning.

PMID- 7620450
TI  - Expanding the role of the educator into organizational development.

PMID- 7620451
TI  - Staff development through performance appraisal: improving the system.

PMID- 7620452
TI  - Icebreakers for your repertoire.

PMID- 7620453
TI  - Proceedings of the 5th Biennial Sandoz-Keystone Symposium on Bone Marrow
      Transplantation. Keystone, Colorado, January 23-28, 1994.

PMID- 7620454
TI  - Isolation of Borrelia burgdorferi on mainland Ontario.

PMID- 7620455
TI  - Isolation of Borrelia burgdorferi, the Lyme disease spirochete, from rabbit
      ticks, Haemaphysalis leporispalustris--Alberta.

PMID- 7620456
TI  - A case of Cyclospora infection in an Albertan traveller.

PMID- 7620458
TI  - Characterization of glycogen and amino acid pool of Entamoeba histolytica by 13C
      NMR spectroscopy.
AB  - Trophozoite extracts of axenic Entamoeba histolytica were investigated by natural
      abundance 13C-NMR spectroscopy. The extracts were found to contain a high level
      of glycogen (30 mM glucose equivalents), which had a compact structure as
      suggested by alpha (1-->6) branch points every 5-6 glucose residues. As other
      major metabolites, we identified putrescine (9.5 mM) and the following free amino
      acids: tyrosine and phenylalanine (1 mM), glycine, lysine and methionine (2 mM),
      isoleucine (5 mM), proline and valine (6-7 mM), leucine (11 mM) and glutamate (22
      mM). Glutamate and proline may serve, together with putrescine, as intracellular
      osmolytes.

PMID- 7620457
TI  - Alterations induced by the antifungal compounds ketoconazole and terbinafine in
      Leishmania.
AB  - The antiproliferative effects and ultrastructural alterations induced in vitro by
      two antifungal compounds, the azole ketoconazole and the allylamine terbinafine
      on Leishmania amazonensis are reported. Promastigotes treatment with ketoconazole
      and terbinafine induced growth arrest and cell lysis in 72 hours. Combination of
      the two agents produced additive effects on promastigote axenic growth and
      synergistic effects on intracellular amastigote proliferation. The amastigotes,
      either axenically grown or infecting murine macrophages, were about 100-fold more
      sensitive to the drugs. These compounds induced the appearance of large
      multivesicular bodies, especially after ketoconazole treatment, increased amount
      of lipid inclusions as well as numerous, polymorphic volutin granules,
      particularly in terbinafine-treated cells. Multivesicular bodies were observed in
      close apposition with organelles such as mitochondria, which also showed
      alterations in the distribution and appearance of cristae, and the formation of
      paracrystalline arrays within the matrix. Some cells presented large portions of
      cytoplasm wrapped by endoplasmic reticulum and many parasites also presented
      myelin-like endoplasmic reticulum profiles. Such alterations together with the
      strong acid phosphatase activity observed in the multivesicular bodies and
      volutin granules may indicate the existence of an unusual autophagic process in
      cells treated with ergosterol biosynthesis inhibitors.

PMID- 7620459
TI  - A sensitive and specific DNA probe for the oyster pathogen Haplosporidium
      nelsoni.
AB  - Haplosporidium nelsoni is a pathogen of the eastern oyster, Crassostrea
      virginica, along the middle Atlantic coast of the U.S. Genomic DNA was extracted
      from H. nelsoni plasmodia and small subunit (SSU) rDNA was amplified by PCR,
      cloned and sequenced. The sequence of H. nelsoni SSU rDNA was aligned with that
      of another haplosporidian, Minchinia teredinis, and with SSU rDNA data of C.
      virginica and various protists in GenBank. A 21-base oligonucleotide unique to H.
      nelsoni, designated MSX1347, was commercially synthesized and tested for
      sensitivity and specificity. In dot blot hybridizations the probe detected 100 pg
      of cloned H. nelsoni rDNA and the presence of H. nelsoni in 1 microgram of
      genomic DNA from an infected oyster. It did not hybridize with 1 microgram of
      genomic DNA from uninfected C. virginica or with cloned SSU rDNA of M. teredinis.
      The probe was further tested for specificity with in situ hybridizations on AFA
      fixed, paraffin-embedded tissue sections. The probe hybridized well with H.
      nelsoni plasmodia and immature spores, but poorly with mature spores. The probe
      did not hybridize with oyster tissue, with other common oyster parasites such as
      P. marinus or Nematopsis sp., or with the haplosporidians Haplosporidium
      louisiana from mud crabs (Panopeus spp.), Haplosporidium costale from C.
      virginica or M. teredinis from shipworms (Teredo spp.).

PMID- 7620460
TI  - Encephalitozoon cuniculi isolated from the urine of an AIDS patient, which
      differs from canine and murine isolates.
AB  - A species of Encephalitozoon has been isolated from the urine of a patient with
      the acquired immunodeficiency syndrome and maintained in vitro in Madin Darby
      Canine Kidney cells. When examined by random amplified polymorphic DNA polymerase
      chain reaction the new isolate was found to differ from E. hellem and to have
      amplified products in common with murine and canine E. cuniculi. However, it more
      closely resembled the canine than the murine isolate. Sodium dodecylsulphate
      polyacrylamide gel electrophoresis differentiated between all three isolates of
      E. cuniculi, with a band at 42-45 kDa present in the murine isolate only, bands
      at 52 kDa present in the canine and human isolates but not the murine, and a
      single band at 60 kDa (murine) and 65 kDa (canine) replaced by two bands at 55
      and 70 kDa in the human isolate. The 55 kDa and 70 kDa antigens were also
      revealed as characteristic bands of the human isolate by Western blotting. The
      study has thus revealed that the species Encephalitozoon cuniculi is not a
      homogeneous entity.

PMID- 7620461
TI  - Evidence of a cadmium-thionein and the glycine cleavage system in Oxytricha
      granulifera.
AB  - This work presents the further purification of a Cd-linking protein in Oxytricha
      granulifera by reverse-phase chromatography. This protein contains 25% cysteine
      and no aromatic amino acid. It may be considered as a chelatin with some
      similarity to metallothioneins. During the purification of another Cd-linking
      compound, we were able to demonstrate that the H protein precursor of glycine
      cleavage is present in Oxytricha. This is the first finding of the presence of
      this system in Protozoa.

PMID- 7620462
TI  - Culture and phylogenetic characterization of Trichomitus trypanoides Duboscq &
      Grasse 1924, n. comb.: a trichomonad flagellate isolated from the hindgut of the
      termite Reticulitermes santonensis Feytaud.
AB  - A trichomonad flagellate strain R1 was isolated from the hindgut contents of the
      termite Reticulitermes santonensis Feytaud. The flagellate was cultivated at 28
      degrees C in anaerobic medium containing yeast extract, minerals and vitamins.
      The isolate fed on living bacteria. It showed the typical morphological and
      ultrastructural features of the trichomonads, closely resembling Trichomitus
      trypanoides. In order to determine its phylogenetic position the small subunit
      ribosomal DNA (SSU rDNA) of the flagellate was amplified in vitro using the
      polymerase chain reaction (PCR), cloned in a plasmid vector and sequenced.
      Comparison of the obtained sequence with so far available SSU rRNA/rDNA sequences
      showed strongest similarity (89%) to the sequence of Tritrichomonas foetus. The
      phylogenetic analysis with parsimony and distance matrix methods placed
      Trichomitus trypanoides strain R1 near by the root of the phylogenetically so far
      analyzed eukaryotic organisms. This confirms that termites harbour hindgut
      symbionts, which originate from very early evolved eukaryotes.

PMID- 7620463
TI  - A three nucleotide signature sequence in small subunit rRNA divides human Giardia
      in two different genotypes.
AB  - The nucleotide sequence of the 16S rRNA gene and the space DNA region was
      determined for Giardia duodenalis, obtained from humans in The Netherlands (AMC
      4) and Washington State (CM). These rDNA sequences differ from other G.
      duodenalis isolates (Portland-1 and BRIS/83/HEPU/ 106) both of which have
      virtually identical rDNA sequences. The most characteristic feature was found
      close to the 5' end of the 16S rRNA. The Portland-1 -Bris/83/HEPU/ 106 type has
      GCG in position 22-24, while AMC-4 and CM have AUC in this position. These two
      sequences, present in an otherwise conserved region of the 16S rRNA, are
      "signature" sequences, which divide Giardia isolates into two different groups.

PMID- 7620464
TI  - Monoclonal antibodies identify a subset of dense granules in Cryptosporidium
      parvum zoites and gamonts.
AB  - Two monoclonal antibodies raised against purified oocysts and excysted
      sporozoites of Cryptosporidium parvum identified antigens located in the anterior
      half of sporozoites by indirect immunofluorescence microscopic assay. The
      monoclonal antibodies also reacted with Triton-X-100-insoluble antigens of
      asexual and sexual stage parasites developing in epithelial cells in vitro and
      identified a 110 kilodalton antigen on immunoblots of sodium dodecyl sulfate
      extracted oocysts. Immunoblotting reactivity was abolished by prior treatment of
      blotted antigen with periodic acid suggesting that the monoclonal antibodies
      recognize a carbohydrate or carbohydrate-dependent epitope(s). By immunoelectron
      microscopy, the antibodies reacted with a family of small, electron-dense
      granules located predominantly in the central region of merozoites and also with
      a population of cytoplasmic inclusions in macrogamonts. In addition, the
      monoclonal antibodies prominently labeled the parasitophorous vacuole membrane of
      all intracellular stages examined suggesting that the corresponding antigen(s)
      may be exocytosed from the granules to become associated with Triton X-100
      insoluble components of the vacuolar membrane or cytoskeleton.

PMID- 7620465
TI  - In vitro characteristics of the microsporidian: Enterocytozoon salmonis.
AB  - Enterocytozoon salmonis, as intranuclear microsporidian of salmonid fish, was
      propagated in vitro using chinook salmon mononuclear leukocytes. Characteristic
      morphology and infectivity of the cultured parasites were evaluated to determine
      the effect of in vitro maintenance and passage on the parasites. Cultured
      parasites developed through several stages from meronts to infectious spores.
      Parasites obtained from in vitro passages tested up to the 17th subculture,
      retained their morphological characteristics and pathogenicity for chinook salmon
      (Oncorhynchus tshawytscha). The disease induced by experimental infections with
      parasites from in vitro cultures was identical to that observed in naturally
      infected chinook salmon. An examination of supernatants obtained from the
      infected cultures revealed evidence of soluble factor(s) produced by E. salmonis
      infected cells that stimulated uninfected target cells in vitro. This observation
      may explain in part the proliferative disease of hematopoietic tissues which
      characterizes the disease in infected chinook salmon.

PMID- 7620466
TI  - Phylogeny of trichomonads inferred from small-subunit rRNA sequences.
AB  - Small subunit (16S-like) ribosomal RNA sequences were obtained from
      representatives of all four families constituting the order Trichomonadida.
      Comparative sequence analysis revealed that the Trichomonadida are a monophyletic
      lineage and a deep branch of the eukaryotic tree. Relative to the early divergent
      eukaryotic assemblages the branching pattern within the Trichomonadida is very
      shallow. This pattern suggests the Trichomonadida radiated recently, perhaps in
      conjunction with their animal hosts. From a morphological perspective the
      Devescovinidae and Calonymphidae are considered more derived than the
      Monocercomonadidae and Trichomonadidae. Molecular trees inferred by distance,
      parsimony and likelihood techniques consistently show the Devescovinidae and
      Calonymphidae are the earliest diverging lineages within the Trichomonadida,
      however bootstrap values do not strongly support a particular branching order. In
      an analysis of all known 16S-like ribosomal RNA sequences, the Trichomonadida
      share most recent common ancestry with unidentified protists from the hindgut of
      the termite Reticulitermes flavipes. The position of two putative free-living
      trichomonads in the tree is indicative of derivation from symbionts rather than
      direct descent from some free-living ancestral trichomonad.

PMID- 7620467
TI  - Cloning and analysis of a Cryptosporidium parvum gene encoding a protein with
      homology to cytoplasmic form Hsp70.
AB  - An intronless gene encoding a protein of 674 amino acid residues with a molecular
      mass of 73,403 Da showing homology to the cytoplasmic form of the 70 kDa heat
      shock proteins has been cloned and sequenced from the intestinal pathogen
      Cryptosporidium parvum. Monospecific polyclonal antibodies obtained to
      recombinant protein recognized a single band with an approximate molecular mass
      of 70 kDa on a Western blot of C. parvum proteins, as well as the 70 kDa heat
      shock protein from bovine brain. Southern blot analysis suggested the gene was
      single copy in the C. parvum genome. Eleven perfect repeats of the sequence GGMP
      were found in the predicted protein near the carboxyl terminus.

PMID- 7620468
TI  - Monoclonal antibodies reveal complex structure in the membrane skeleton of
      Tetrahymena.
AB  - Twelve monoclonal antibodies were raised that are specific for the membrane
      skeleton of Tetrahymena. Five were directed against T. pyriformis and seven were
      directed against T. thermophila. Some cross-reactivity between species was found.
      Each monoclonal antibody recognized one of the three major components of
      epiplasm, i.e. the bands A, B, and C identified in electrophoretic separations of
      epiplasmic proteins. It was found, using these antibodies, that the epiplasmic
      proteins A, B and C have overlapping but independent distributions within the
      cell.

PMID- 7620469
TI  - Detection and immunolocalization of human erythrocyte spectrin immunoanalogues in
      Toxoplasma gondii (Protozoan, Parasite).
AB  - We demonstrated here the presence of proteins antigenically related to human
      erythroid spectrin in the parasitic protozoan Toxoplasma gondii. A high molecular
      weight doublet (M(r) 245-240,000), present in equimolar ratio, and low molecular
      weight poly-peptides (M(r) 75,000) were reacted with monoclonal and polyclonal
      anti-human erythroid spectrin antibodies on electroblotted nitro-cellulose
      sheets. Indirect immunofluorescence assay clearly showed that these proteins were
      localized in the anterior pole of the organism. Immunogold staining further
      revealed specific labeling of conoid, rhoptries, micronemes, and dense granules
      of the apical complex. The presence of the M(r) 245-240,000 doublet and the M(r)
      75,000 spectrin-like proteins in the anterior pole of T. gondii may probably be
      consistent with a structural stabilizer function in its organelles which are
      suspected to be involved in the process of host cell invasion.

PMID- 7620470
TI  - Family versus individual therapy for anorexia: impact on family conflict.
AB  - This study evaluated the impact on family relations of behavioral family systems
      therapy (BFST) versus ego-oriented individual therapy (EOIT) as treatments for
      adolescents with anorexia nervosa. Twenty-two adolescents meeting DSM-III-R
      anorexia nervosa criteria were randomly assigned to receive approximately 16
      months of either BFST or EOIT along with a common medical and dietary regimen.
      BFST emphasized parental control over eating, cognitive restructuring, and
      problem-solving communication training. EOIT emphasized building ego strength,
      adolescent autonomy, and insight. Measures including body mass index, self
      reported general and eating-related conflict, and observed general and eating
      related communication. Both treatments produced significant reductions in
      negative communication and parent-adolescent conflict, with some differences
      between condition and between eating and non-eating related measures; the
      improvements in eating-related conflict were maintained at a 1-year follow-up.
      The study demonstrated that structured therapies for adolescent anorexia do
      impact family relations, even when the family is never seen as a unit during the
      therapy.

PMID- 7620471
TI  - Factors affecting dropout rate from cognitive-behavioral group treatment for
      bulimia nervosa.
AB  - The aim of this study was to retrospectively identify clinical variables assessed
      prior to treatment which were predictive of patients' dropping out versus
      completing a 10 week group cognitive-behavioral treatment program for bulimia
      nervosa. Following a lengthy initial assessment, 81 women meeting DSM-III-R
      criteria for bulimia nervosa (BN) were referred to one of twelve 10-week groups
      of 8 to 12 patients having bulimic symptoms. The dropout rate for those meeting
      full DSM-III-R criteria for BN was found to be 28.7%. A series of seven
      discriminant function analyses were performed to determine whether dropouts
      differed from completers in terms of depression, anxiety, difficulties in trust
      and relating to others, bulimic symptom severity, family environment, weight
      history and symptom duration and severity of bulimic cognitions. Of these, only
      the factor assessing difficulties trusting and relating to others was found to
      significantly discriminate dropouts from completers. Implications of the findings
      are discussed in terms of clinical and research relevance in the field of eating
      disorders.

PMID- 7620472
TI  - Differences in weight gain between restrictor and bulimic anorectics.
AB  - After admission for weight restoration, restrictor anorectics (n = 17) gained
      significantly less weight than bulimic anorectics (n = 17) in a 30-day period.
      However, these groups had similar caloric intake. Severity of illness was found
      to be a predictor of rate of weight gain for restrictor anorectics, but not for
      bulimic anorectics.

PMID- 7620473
TI  - Refeeding, metabolic rate, and weight gain in anorexia nervosa: a review.
AB  - Patients with anorexia nervosa require refeeding to restore normal body weight. A
      variety of studies have examined the role of metabolic rate in the refeeding of
      anorectic patients. Several measurement techniques have been used to divide
      metabolic rate into its components: basal metabolic rate, resting energy
      expenditure, activity-induced thermogenesis, and dietary-induced thermogenesis.
      In anorexia nervosa patients several consistent findings are present. First, the
      number of kilocalories required for weight gain or weight maintenance increases
      as weight increases. Second, over 50% of the body mass gained in anorectic
      individuals represents fat tissue. Finally, both a history of bulimic symptoms
      and a higher premorbid body weight may lead to lower calorie requirements. These
      findings suggest the need for gradual increase in calories provided throughout
      treatment; resting energy expenditures may aid the determination of caloric
      requirements

PMID- 7620475
TI  - Ipsapirone in the treatment of bulimia nervosa: an open pilot study.
AB  - Seventeen women who met the criteria for bulimia nervosa (DSM-III-R) were treated
      for 4 weeks in an open trial with ipsapirone, a partial 5-HT1A agonist. Bulimic
      symptoms diminished in 66.6% of the patients after only 1 week of treatment,
      93.3% showed a reduction of more than 50% of weekly binge eating attacks after 4
      weeks. The mean frequency of binges was reduced by 81% at endpoint. Ipsapirone
      was well tolerated.

PMID- 7620474
TI  - A controlled trial of cisapride in anorexia nervosa.
AB  - To determine the efficacy of cisapride, 10 mg three times daily, in improving
      gastric emptying, reducing distress during meals, and facilitating weight gain in
      anorexia nervosa, we conducted an 8-week, randomized, double-blind, placebo
      controlled trial on 29 inpatients. Measures included scintigraphic gastric
      emptying studies at 0, 2, 4, and 8 weeks; subjective distress during meals
      measured by visual analogue scales; self-rating of degree of global improvement
      in symptoms associated with eating at end of study; and weight measured weekly.
      Gastric emptying improved significantly but equally in both groups over the study
      period. Yet subjective measures were better in the cisapride group; they rated
      themselves as more hungry (p = .02) and more improved on the global measure of
      change in symptoms (p = .02). Even so, the cisapride group did not gain more
      weight. The correlation between gastric emptying and weight gain was modest (r =
      .30; p = .11), and between gastric emptying and the subjective measures,
      virtually absent.

PMID- 7620476
TI  - Patterns of punitiveness in women with eating disorders.
AB  - The level and direction of hostility in patients with bulimia nervosa, anorexia
      nervosa and a comparison group were measured using the the Hostility and
      Direction of Hostility Questionnaire. A semistructured interview developed by
      Harris, Brown, and Bifulco (Psychological Medicine, 16, 641-659, 1986) was used
      to assess childhood care to examine whether a link exists between childhood
      exposure to aggression or parental neglect and adult hostility. Patients with
      eating disorders had significantly higher hostility levels and were significantly
      more intropunitive than the comparison group. Patients with bulimia nervosa were
      significantly more intropunitive than the comparison group. Patients with bulimia
      nervosa were significantly more hostile than patients with anorexia nervosa.
      Anorexia nervosa patients were more likely to direct hostility inwardly, rather
      than outwardly, when compared with bulimia nervosa patients. Impulsivity was
      associated with extrapunitiveness whereas intropunitiveness was associated with
      depression. Although some measures of poor childhood care correlated with adult
      hostility levels no clear pattern emerged.

PMID- 7620477
TI  - Abnormal eating and dissociative experiences.
AB  - A total of 656 male and female college students completed the Eating Disorder
      Inventory (EDI) and a modified version of the Dissociative Experiences Scale (M
      DES). There were significant correlations between dissociative experiences and
      each of the EDI subscales, especially for women. Even among women, however,
      dissociation was more strongly related to aspects of ego dysfunction than to
      abnormal eating per se. This finding sets limits on the hypothesized association
      between dissociative disorder and eating disorder.

PMID- 7620478
TI  - Effects of body image on dieting, exercise, and anabolic steroid use in
      adolescent males.
AB  - This cross-sectional survey study examined body image, dieting and exercise
      variables, and steroid use in 2,088 high-school graduates aged 18 years. In
      contrast to women, more men wished to gain (46%) rather than loose weight (32%).
      Men who wished to gain weight were more satisfied with their body shape, showed
      no fear of fatness, and dieted and exercised less frequently than did men who
      wished to lose weight. The prevalence of dieting was low (4%), even among men who
      wished to lose weight (9%), and physical exercise was more likely to be used for
      both weight loss and weight gain. Contrary to expectations, anabolic steroid use
      was rare (0.6%) and was not associated with a desire for weight gain. Steroid
      users were more likely to engage in running and swimming than football. The data
      did not support the notion that anabolic steroid use is widespread among high
      school males.

PMID- 7620479
TI  - Structural equation modeling of risk factors for the development of eating
      disorder symptoms in female athletes.
AB  - Risk factors for the development of eating disorder symptoms in female college
      athletes were studied using structural equation modeling. Three risk factors:
      social influence for thinness, athletic performance anxiety, and self-appraisal
      of athletic achievement, were selected for study. The association of these risk
      factors and eating disorder symptoms was hypothesized to be mediated by
      overconcern with body size and shape. The study sample was 98 women recruited
      from eight sports teams at a major university. Structural equation modeling
      analysis supported the hypothesized model and cross-validation of the model
      showed the findings to be stable. The results of this correlational study
      suggested that eating disorder symptoms in college athletes are significantly
      influenced by the interaction of sociocultural pressure for thinness, athletic
      performance anxiety, and negative self-appraisal of athletic achievement. If
      these risk factors lead to overconcern with body size and shape, then the
      emergence of an eating disorder is more probable.

PMID- 7620481
TI  - Bulimia nervosa in two cultures: a comparison of Austrian and American college
      students.
AB  - We compared 33 college women meeting DSM-III-R criteria for bulimia nervosa,
      recruited at Leopold Franzens Universitat in Innsbruck, Austria, with 33 bulimic
      women recruited by identical methods at Northeastern University and Boston
      University in Boston, Massachusetts. Bulimia nervosa showed striking stereotypy
      across the two cultures. Austrian and American subjects reported similar
      demographic features, bulimic symptoms, severity and chronicity of illness,
      associated personal and familial psychiatric disorders, upbringing and family
      environment, and frequency of childhood sexual abuse. Only two variables,
      substance abuse and satisfaction with body image, differed markedly between the
      two groups. These differences appear to represent ambient differences between
      American and Austrian culture as a whole, rather than specific features of the
      bulimic syndrome.

PMID- 7620480
TI  - Onset of binge eating, dieting, obesity, and mood disorders among subjects
      seeking treatment for binge eating disorder.
AB  - Binge eating disorder (BED) identified in adulthood is often clinically
      associated with obesity and a lifetime history of affective disorders. Several
      authors have suggested that dieting may predispose individuals to binge eating
      which then may lead to obesity. However, few BED studies have examined the
      chronology of the onset of binge eating, dieting, obesity, and mood disorders.
      This study evaluated retrospective reports from 30 women participating in a BED
      treatment study. Although the majority of subjects in this adult sample were
      obese, initiation of binge eating behavior usually occurred during adolescence at
      a time when most subjects reported being of normal weight. Obesity developed
      several years after the age of onset of meeting BED criteria. Onset of binge
      eating usually predated that of dieting or major depressive disorder in the
      majority of subjects. The results support the importance of early intervention
      for binge eating.

PMID- 7620482
TI  - Comparison of eating disorder patients with and without compulsive exercising.
AB  - Several studies have examined the occurrence of eating disorders in athletes.
      However, little has been written about the frequency and phenomenology of
      compulsive exercising in eating disorder (ED) patients. Given this, we studied a
      series of 110 patients who presented to the Medical University of South Carolina
      Eating Disorders Program and met lifetime DSM-III-R criteria for bulimia nervosa
      (n = 71), anorexia nervosa (n = 18), or both disorders (n = 21). All patients
      completed the Diagnostic Survey of the Eating Disorders (DSED), a self-report
      measure of demographic and clinical characteristics including time spent
      exercising daily. Thirty-one (28%) of the 100 patients reported that they
      exercised > or = 60 min every day (M +/- SD = 105 +/- 48 min) and were defined as
      compulsive exercisers (CEs). In addition, 3 CE patients with a DSM-III-R
      diagnosis of eating disorder not otherwise specified (EDNOS) were included for
      comparison with non-CEs on a number of variables. CEs had significantly greater
      ratings of body dissatisfaction (p < .01) than non-CEs. Non- CEs were
      significantly more likely than CEs to vomit and use laxatives (p < .01, chi 2),
      and they had a higher frequency of binge eating ( p < .006, Kruskal-Wallis).
      There was a trend for a significantly higher frequency of compulsive exercising
      in the patients with anorexia nervosa (38.5%) than those with bulimia nervosa
      (22.5%) (p < or = .06, chi 2).

PMID- 7620483
TI  - Changing times, partial solutions.

PMID- 7620484
TI  - Managing treatment related side effects of nausea and vomiting.

PMID- 7620485
TI  - Spinal cord tumors: review of etiology, diagnosis, and multidisciplinary approach
      to treatment.
AB  - Spinal cord tumors (SCT) are a diverse group of uncommon neoplasms that develop
      from tissues in and around the spinal canal. They often have an indolent onset
      and progression of signs and symptoms, which may include back pain, extremity
      weakness, sensory alterations, and bowel or bladder incontinence. The most common
      SCTs are located in the extramedullary space and include meningiomas and
      neurofibromas. Intramedullary SCTs, for example ependymomas and astrocytomas,
      occur less frequently. The most useful screening test for diagnosis of a SCT is
      enhanced magnetic resonance imaging; myelography and computed tomography also can
      be helpful. The majority of SCTs are amenable to surgical therapy and can be
      partially or completely resected. Radiation therapy is reserved for incompletely
      resected low-grade tumors, malignant tumors, and recurrent tumors. The
      rehabilitative process should be initiated early on following diagnosis, if
      possible, in patients with neurologic deficits to minimize long-term disability.

PMID- 7620486
TI  - Women's narratives of helpseeking for breast cancer.
AB  - One-third of women with self-discovered breast cancer are symptomatic for 3
      months or more before seeking evaluation. Few studies examine women's accounts of
      this important time. Using narrative analysis in the style of Labov and Waletzky,
      breast cancer cases from a larger mixed-tumor sample of patients receiving
      chemotherapy were examined for the details of breast cancer symptom discovery and
      the events relevant to the timing of diagnosis and treatment. The majority
      (56.3%) of women in the sample sought evaluations within days, many proceeding to
      immediate diagnosis. Factors cited by women as influencing the delayed timing of
      initial provider evaluation were that they attributed the symptoms to a benign
      process, and they perceived gender role-related constraints. Many women in this
      younger-aged sample had false-negative mammographic examinations, and many
      reported receiving false reassurance from providers on initial consultation
      visits. Women who delayed evaluations sought them only as symptoms advanced.

PMID- 7620487
TI  - Needs of hospice and clinic patients with cancer.
AB  - The purposes of this descriptive study were: (1) to compare the self-selected
      needs of 69 patients with cancer, 31 from a nonprofit hospice, and 38 from a
      university cancer center located in the mid-south; and (2) to establish the
      reliability of the Cancer Patient Need Survey for hospice patients. Patients
      completed the Cancer Patient Need Survey and a demographic data form. Hospice and
      clinic patients rated the category of coping needs most important. Clinic
      patients also ranked the category of information needs as a priority, but did not
      find these needs as well met. Both groups ranked as their top individual needs
      support from family and friends, and a patient caregiver. Reliabilities of the
      instrument for the groups range from 0.91 to 0.93. The Cancer Patient Need Survey
      is a useful instrument for assessing and testing the needs of clinic patients,
      but additional work needs to be done in modifying the instrument for use with
      hospice patients.

PMID- 7620488
TI  - The Positive Appearance Center: an innovative concept in comprehensive
      psychosocial cancer care.
AB  - Every year, more than one million people are diagnosed with cancer in the United
      States. Many of the treatments for cancer cause temporary or permanent physical
      changes that, along with the diagnosis, may lead to altered body image and
      diminished self-esteem in patients with cancer. The Positive Appearance Center
      was developed to help male and female patients with cancer deal with the cosmetic
      side effects and comfort needs related to their diagnosis and treatment. The
      Positive Appearance Center is part of a larger psychosocial program located in a
      comprehensive cancer center and is open to the public. Feedback from patients has
      been positive. Patients have cited the products and services provided by the
      center as major factors helping them cope with the physical and emotional aspects
      of their cancer.

PMID- 7620489
TI  - Effect of major dietary modifications on immune system in patients with breast
      cancer: a pilot study.
AB  - A pilot study was conducted to evaluate the effect of diet on immune function in
      nine premenopausal, post-therapy patients with breast cancer. The patients were
      instructed on following the American Cancer Society dietary guidelines and were
      told to do so from day 0 to day 28. These guidelines recommend a high-fiber, low
      fat diet. On day 29, the patients continued the diet but included fish high in
      omega-3 fatty acids until day 56. Twenty-four-hour urine and blood samples, and 3
      day diet records were obtained on days 0, 28, and 56. The following parameters
      were monitored: lymphocyte subsets, T-cell function (proliferation and cytolytic
      response), and urinary prostaglandin E2 (PGE2). Results throughout the study
      suggested a benefit from decreasing dietary fat intake, and increasing fish
      intake. Helper T-cell (CD4) percentage increased from day 0 to days 28 and 56 (P
      = 0.048). Cytotoxic/suppressor T-cell (CD8) percentage decreased from day 0 to
      days 28 and 56 (P = 0.002). The CD4/CD8 cell ratio increased by days 28 and 56 (P
      = 0.0004). The proliferation of CD4 cells increased from day 0 to days 28 and 56
      (P = 0.005). Significant changes were not found in the cytolytic activity of T
      cells, natural killer cells, total T and B cells, or urinary prostaglandin E2.
      Results suggest that patients with breast cancer may benefit from following
      American Cancer Society dietary guidelines and consuming cold-water ocean fish.

PMID- 7620491
TI  - Resources for helping patients to quit smoking.

PMID- 7620490
TI  - Expectation and occurrence of postchemotherapy side effects: nausea and vomiting.
AB  - Although nausea and vomiting are among the most disruptive chemotherapy side
      effects, little is known about patients' expectations before therapy and their
      experience after chemotherapy. A stratified sample of 329 subjects on nine
      chemotherapy regimens were asked to list their expected symptoms and level of
      distress. The patients listed a total of 524 responses and 28 different symptoms.
      This paper focuses on the symptoms of nausea and vomiting. A statistically
      significant relationship (P = 0.015) was found between the patients' expectations
      of symptom experience and their expectations of symptom distress. No significant
      relationship was found between the expectation of the symptom and the actual
      symptom experience. These findings support the need for educational interventions
      that provide hopeful but realistic expectations of the unknown events for
      patients with cancer.

PMID- 7620492
TI  - Challenges in a multidisciplinary head and neck oncology program.

PMID- 7620493
TI  - With baby.

PMID- 7620494
TI  - Remembering why we are midwives.

PMID- 7620495
TI  - Protector of the normal birth process.

PMID- 7620496
TI  - An empowering birth.

PMID- 7620497
TI  - Making a difference.

PMID- 7620499
TI  - Memories of Moscow.

PMID- 7620498
TI  - Singing a lullaby of pain.

PMID- 7620500
TI  - Josef's birth.

PMID- 7620501
TI  - Traditional bush midwives of Niger.

PMID- 7620502
TI  - The traditional midwives of Mexico.

PMID- 7620504
TI  - In grave danger.

PMID- 7620505
TI  - Homebirth in Japan.

PMID- 7620503
TI  - Our common link.

PMID- 7620506
TI  - The unsung backstage heroes.

PMID- 7620507
TI  - The ancient art of sobada.

PMID- 7620508
TI  - The pearl of Africa.

PMID- 7620509
TI  - Perinatal transmission of HIV.

PMID- 7620510
TI  - For a global future.

PMID- 7620511
TI  - Midwives unite.

PMID- 7620512
TI  - Nitric Oxide in Cardiovascular System, from Basic Research to Clinics.
      Proceedings of the 2nd symposium. Krakow, May 22-25, 1994.

PMID- 7620513
TI  - Regulatory mechanisms of the vascular endothelium: an update.
AB  - This review discusses recent experimental findings in prostacyclin, nitric oxide
      and endothelin research. Prostacyclin formation by endothelial cells in
      atherosclerosis and diabetes is reviewed and the synthesis of prostacyclin by
      cyclooxygenase 1 and 2 (COX-1 and COX-2) is discussed. Further work on nitric
      oxide describes its involvement in septic and haemorrhagic shock and its
      interactions with the cyclooxygenase pathway. Recent studies in endothelin
      research include the development of both selective and orally active receptor
      antagonists, characterization of endothelin converting enzymes and the
      involvement of endothelin-1 in inflammation and wound repair.

PMID- 7620514
TI  - The position of NO among endogenous vasodilators.
AB  - Bradykinin stimulates phospholipases to release arachidonic acid (AA) which can
      be metabolized by cyclooxygenase, lipoxygenase and cytochrome P450 (P450) to
      yield vasoactive products that may contribute to the effect of the peptide. In
      the rat kidney, pharmacological evidence suggests that a substantial component of
      the vasodilator response is dependent on P450-AA metabolism. In the heart, the
      vasodilator response to bradykinin is independent of NO and prostaglandins but
      reduced by inhibitors of P450, including 17-ODYA, an inhibitor of fatty acid
      metabolism, also suggesting a role of P450-AA. Moreover, the renal and coronary
      vasodilator responses to bradykinin are associated with release of P450-AA
      products measured by gas chromatography-mass spectrometry (GC-MS). The coronary
      vasodilator response to bradykinin is also dependent on activation of K+ channels
      linking P450-AA and hyperpolarization. Formation of vasodilator eicosanoids
      derived via the P450 pathway may make important contributions to the control of
      vascular tone, local blood flow and, thereby, blood pressure.

PMID- 7620515
TI  - NO-donors in cardiology.
AB  - Nitrates have been used in the pharmacological treatment of cardiac diseases for
      over hundred years, at the beginning in the treatment of angina pectoris. Later
      on the scale of clinical indications has widened towards other diseases where the
      vasodilating effect of these drugs could be of benefit. The increased interest in
      nitrates is based on new knowledge about their pharmacokinetics, pharmacodynamics
      and development of tolerance as well as the new idea of their cellular mode of
      action. They release nitric oxide, vasodilator and vasorelaxant physiologically
      originating from the vascular endothelium (EDRF). Nitrates and other NO-donors
      can substitute for this endogenous factor in the case of diseases endothelium or
      on other occasions where the production of NO is reduced or abnormally changed to
      toxic products. It is evident that totally new type of NO-donors like molsidomine
      and others will appear on the market for the treatment not only of cardiovascular
      diseases but also other disorders where smooth muscle relaxation is necessary.
      This review deals with the present status of nitrates in the cardiology and
      predicts some future aspects in this field.

PMID- 7620516
TI  - Mesoionic oxatriazole derivatives--a new group of NO-donors.
AB  - A number of new 3-aryl-1,2,3,4-oxatriazole-5-imine derivatives (GEA Compounds-
      GEAC) were synthetized. GEAC are NO-releasers as evidenced by direct measurement
      of NO in headspace/NO-analyzer, by cooxygenation of oxyhaemoglobin to
      methaemoglobin in the Werringloer's test and by generation of nitrite in the
      Griess' reaction. During the release of NO from GEAC the consumption of O2 could
      be detected only when high concentrations of GEAC were used. The mechanism of
      release of NO from molecules of GEAC still remains hypothetical. Some of GEAC
      were found to remain stable for long periods of time, even at 37 degrees C. Both
      mutagenic properties and the pharmacodynamic profile of GEAC can be controlled by
      a mindful choosing of appropriate substituents.

PMID- 7620517
TI  - Endothelium-dependent relaxation to arachidonic acid in porcine coronary artery:
      is there a fourth pathway?
AB  - Endothelium-dependent relaxations to bradykinin (BK) in U46619-contracted,
      indomethacin (INDO)-treated porcine coronary artery (PCA) rings are modestly
      attenuated by the nitric oxide (NO) synthase inhibitor, N omega-nitro-l-arginine
      methyl ester (L-NAME); whereas, when contracted with KCl, L-NAME abolishes BK
      relaxations. In contrast, endothelium-dependent arachidonic acid (AA) relaxations
      of U46619-contracted, INDO-treated PCA rings are not affected by L-NAME. AA does
      not relax KCl-contracted rings. Since BK is known to release AA, we postulated
      that the non-NO component of BK relaxation of the PCA is mediated by AA or an AA
      metabolite. Changes in tension of PCA rings to BK and AA were determined in the
      presence and absence of phospholipase (PLA), cyclooxygenase (CO), lipoxygenase
      (LO) and cytochrome P-450 (cP450) inhibitors. Responses to BK were attenuated by
      PLA inhibitors. No other inhibitors, however, eliminated responses to either BK
      or AA. The results suggest that relaxation to BK in PCA rings requires PLA
      activity, but relaxation to AA is independent of PLA, CO, LO or cP450 activity.
      We conclude that relaxation to BK and AA in the PCA is mediated by a product of
      an unidentified pathway of AA metabolism or by an unknown second messenger system
      resident within the endothelium and responsive to AA.

PMID- 7620518
TI  - Inhibition of nitric oxide synthesis results in a selective increase in arterial
      resistance in rabbit lungs.
AB  - Endogenous nitric oxide (NO) opposes the vasoconstriction that occurs when lungs
      are ventilated with a hypoxic gas mixture. However, the contribution of NO to
      pulmonary vascular resistance when alveolar gas tension is not reduced remains to
      be defined. Here, we investigated the hypothesis that endogenous NO is a
      determinant of pulmonary vascular resistance in isolated perfused rabbit lungs
      ventilated with a normoxic gas mixture. Moreover, we wished to establish that, as
      flow rate increases, the contribution of NO to vascular resistance increases. In
      addition, we examined the contribution of NO to the longitudinal distribution of
      pulmonary vascular resistance. Pressure-flow curves were generated in isolated
      blood perfused rabbit lungs by varying flow rate from 50 ml/min to 300 ml/min in
      the presence and absence of the cyclooxygenase inhibitor, indomethacin (100
      microM) and the inhibitor of NO synthesis, NG-nitro-L-arginine methyl ester (L
      NAME, 100 microM). Indomethacin did not alter total pulmonary vascular resistance
      or the longitudinal distribution of resistance. In contrast, L-NAME
      administration resulted in significant, flow-related increases in total vascular
      resistance, i.e., after L-NAME, as flow rate increased, the increment in
      resistance increased. L-NAME-induced increases in total pulmonary vascular
      resistance were the result of flow-related increases in the arterial component of
      vascular resistance. These results provide support for the hypothesis that NO is
      an important determinant of pulmonary vascular resistance in the rabbit and that
      the major site of NO activity resides in the arterial side of that circulation.

PMID- 7620519
TI  - Peroxynitrite and arachidonic acid. Identification of arachidonate epoxides.
AB  - Peroxynitrite is a novel substance capable of oxidation of arachidonic acid.
      Treatment of [1-14C]arachidonic acid with peroxynitrite at pH 7.4 resulted in
      formation of a complex mixture of radioactive products. The isolation of these
      compounds and structural analysis by liquid chromatography/mass spectrometry
      revealed formation of three epoxyeicosatrienoic acids: 8,9-EET, 11,12-EET and
      14,15-EET. These epoxides can play a role in peroxynitrite induced oxidative
      modification of arachidonic acid in cells.

PMID- 7620520
TI  - Glutathione oxidation under the action of sodium nitrite on hemoglobin.
AB  - The reaction of oxidation of oxyhemoglobin (oxyHb) to methemoglobin (metHb) by
      sodium nitrite in the presence of reduced glutathione is characterized by the
      changed ratios between the slow and rapid reaction phases. The duration of the
      lag phase increases as the glutathione concentration in the solution rises. The
      autocatalytic phase was inhibited and glutathione was oxidized to the disulfide
      form. The decreased rate of the reaction of oxyHb oxidation by sodium nitrite may
      be due to the effects of both the intermediate and the end products of oxidized
      glutathione. It is suggested that the thyil radical interacts to form the
      intermediate compound, anione glutathione disulfide (GSSG), which reduces metHb,
      thus increasing the lag phase duration. The autocatalytic phase inhibition can
      also be induced by electron transfer from the superoxide anion to the GSSG form.
      In addition to the GSSG, S-nitrosoglutathione was also formed during oxyHb
      oxidation by nitrite. In the absence of oxyHb in the neutral neutral medium,
      reduced glutathione (GSH) was not essentially oxidized by sodium nitrite. At pH
      lower than 6.0 S-nitrosoglutathione was observed to be formed due to the
      interaction of sodium nitrite with GSH. The addition of salts or increased pH of
      the solution induced hydrolysis of the product.

PMID- 7620522
TI  - Small round structured viruses (SRSV): numbers are increasing.

PMID- 7620521
TI  - An outbreak of Escherichia coli O157 in southern England.

PMID- 7620523
TI  - Beta-amyloid deposition in the medial temporal lobe in elderly non-demented
      brains and in Alzheimer's disease.
AB  - The density of diffuse, primitive, classic and compact beta-amyloid (beta/A4)
      deposits was estimated in the medial temporal lobe in elderly non-demented brains
      and in Alzheimer's disease (AD). In the non-demented cases, beta/A4 deposits were
      absent in the hippocampus but in 8/14 cases they were present in the adjacent
      cortical regions. Variation in beta/A4 deposition in the non-demented cases was
      large and overlapped with that of the AD cases. The ratio of mature to diffuse
      beta/A4 deposits was greater in the non-demented than in the AD cases. In both
      the non-demented cases and AD, the beta/A4 deposits were clustered with, in many
      tissues, a regular distribution of clusters along the cortex parallel to the pia.
      However, the mean cluster size of the deposits in the cortex was greater in AD
      than in the non-demented cases. These results suggest that the spread of beta/A4
      pathology between the modular units of the cortex and into the hippocampus could
      be important factors in the development of AD.

PMID- 7620524
TI  - Alzheimer disease amyloid proteins inhibit brain endothelial cell proliferation
      in vitro.
AB  - Despite the close morphological association of beta-amyloid and vascular cells,
      the functional effects of amyloid in cerebral endothelial cells in Alzheimer's
      disease have not been assessed. In this study, effects of amyloid fractions
      purified from senile plaques of AD brains were compared to synthetic amyloid
      peptides for their ability to affect brain endothelial cells in vitro. Our
      results indicate that plaque-derived amyloid inhibit brain endothelial cell
      proliferation in vitro by 40%. This inhibition was specific for plaque-derived
      amyloid, was not evoked by synthetic A beta 1-40, and was not mediated by
      alterations in intracellular calcium levels. Amyloid fractions from AD brains,
      although not directly toxic to brain endothelial cells, inhibit endothelial
      replication in vitro and therefore could alter the ability of vessels to repair
      and regenerate after injury.

PMID- 7620526
TI  - Clinical diagnosis of frontal lobe dementia and Alzheimer's disease: relation to
      cerebral perfusion, brain atrophy and electroencephalography.
AB  - The regional cerebral blood flow, brain atrophy, white matter changes and
      neurophysiologic changes were evaluated in 28 patients with a clinical diagnosis
      of probable Alzheimer's disease (AD) and in 8 patients with a clinical diagnosis
      of frontal lobe dementia (FLD) using single photon emission computed tomography,
      magnetic resonance imaging and electroencephalography (EEG). We found that FLD
      patients had more severe frontal blood flow reduction and less severe parietal
      blood flow reduction compared to AD patients. Among patients with mild dementia
      the EEG changes were less severe in the FLD group. No significant differences
      were found in white matter changes or in regional atrophy.

PMID- 7620525
TI  - Neuronal number and size are preserved in the nucleus basalis of aged rhesus
      monkeys.
AB  - Neurons in the nucleus basalis of Meynert (NBM) were analyzed morphometrically in
      21 rhesus monkeys ranging in age from 9 to 33 years. Numbers of cholinergic
      neurons were similar across all ages at several NBM levels in either Nissl
      stained paraffin sections or sections processed immunocytochemically for nerve
      growth factor receptor (p75LNGFr). Size of NBM neurons was larger in aged monkeys
      than young monkeys at all NBM levels, particularly in the most posterior
      subdivision. A subset of monkeys were behaviorally characterized shortly before
      death, and partial correlation analyses indicated that increased age was
      associated with declines in recognition memory, visuospatial orientation, and
      reaction time. Controlling for age, spatial memory and concurrent discrimination
      abilities were associated with lower cell number in intermediate NBM. Numbers of
      neurons in anterior NBM did not correlate with any behavioral measure. These
      observations indicate that numbers of NBM cholinergic neurons are stable with
      age, that NBM neurons become hypertrophic in older animals, and that morphometric
      indices of cholinergic neurons are associated with cognitive function.

PMID- 7620527
TI  - Quantitative EEG mapping, regional cerebral blood flow, and neuropsychological
      function in Alzheimer's disease.
AB  - The relations between quantitative EEG, regional cerebral blood flow (rCBF),
      severity of disease and neuropsychological data were analyzed in 31 patients in
      different stages of Alzheimer's disease (AD). As a group the demented patients
      had higher delta and theta activities, lower alpha activity and lower alpha peak
      frequency than control subjects. rCBF was reduced in all regions studied but
      mainly in the temporoparietal areas. An analysis of correlations showed a close
      relationship between rCBF and certain quantitative EEG parameters in AD patients,
      mainly the power of the theta and delta bands. Both rCBF evaluation and
      quantitative EEG provide functional information related to the severity of
      cognitive impairment.

PMID- 7620528
TI  - Neuropathological analysis of dementia in a Japanese leprosarium.
AB  - In a neuropathological study of consecutive autopsies, prevalence and cause of
      dementia in a Japanese leprosarium were investigated, where more than 95% of
      inpatients with a mean age of 70 years are now free from active leprosy. In 10
      years (1983-1992), clinically overt dementia at death was 35/136 (25.7%) in the
      age group over 65 years (mean age 79.4). Autopsy was performed in 85 cases (mean
      age 81 years), and clinically overt dementia was seen in 25 subjects (29.4%).
      Neuropathologically, Alzheimer's disease (AD) was seen in 9 cases (10.6%),
      vascular dementia (VD) in 9 cases (10.6%), mixed type in 3 cases (3.5%) and
      unclassified in 4 cases (4.7%). In the age group of 65-84 years, AD was 5/58
      (8.6%), VD was 4/58 (6.9%), mixed type was 2/58 (3.4%), and unclassified was 1/58
      (1.7%). Compared with previous Japanese general population-based data, where VD
      was more frequent than AD, the rate of dementia in our leprosarium was high, and
      pathologically confirmed AD was as common as VD. Recently, a prophylactic effect
      of the antileprosy and anti-inflammatory drug DDS (dapsone, 4,4'-diaminodiphenyl
      sulfone) has been suggested. Lepromatous patients take more DDS (51.9%) than
      tuberculoid patients (11.5%), however, as the dementia rate of tuberculoid
      leprosy (17.9%) in those 65-84 years old is similar to lepromatous leprosy
      (15.9%) in our study, we do not support their viewpoint.

PMID- 7620530
TI  - Severity of dementia correlates with loss of broad-band visual cortical
      responses.
AB  - We have shown that the response to flash stimulation of the occipital
      electroencephalogram (EEG) in Alzheimer disease (AD) patients is smaller than in
      normal subjects. To ascertain whether this is a specific feature of AD or a
      nonspecific effect of dementia, we investigated in AD and multi-infarct dementia
      (MID) patients the relationship between cognitive function, measured as Mini
      Mental State Examination score, and EEG power response, measured as the
      difference in spectral power between flash-stimulated EEG and resting EEG. Both
      variables were positively correlated and the regression equations of AD and MID
      patients were not significantly different, showing nonspecificity. The coupling
      between cognitive function and power response is discussed in relation to the
      dynamic binding hypothesis of cognition.

PMID- 7620529
TI  - Neuropathological diagnoses in elderly patients in Oslo: Alzheimer's disease,
      Lewy body disease, vascular lesions.
AB  - Neuropathological changes in elderly residents of Oslo, Norway were characterised
      with respect to the cerebral substrates of dementia. Ninety-two brains were
      examined, representing 41% of all deaths occurring in 10 nursing homes during a 9
      month period. The autopsy cohort showed a similar mean age (85 years) and sex
      ratio (73% female) and proportion of demented patients (75%) compared to all the
      patients resident in these homes who died during the same period. Clinical data
      was compiled retrospectively. Diagnosis was made using the CERAD protocol, and
      criteria for the diagnosis of Lewy body dementia. Lewy body formation was present
      in 20% and cerebral infarction in 21% of patients. In the demented group (69
      patients) 90% fulfilled CERAD criteria for definite or probable Alzheimer's
      disease. Eight demented cases had absent neocortical neurofibrillary tangles and
      6 other cases showed Lewy body dementia (9% of demented patients). A further 8 of
      these demented cases had brain stem Lewy bodies with only minimal cortical
      involvement. Thirteen cases (19% of the sample) had cerebral infarcts but these
      were considered to be clinically significant in only 4 (6%). In the non-demented
      patients (23) 4 patients had brain stem Lewy bodies and 6 had cerebral infarcts.
      Despite inclusion criteria biased towards the collection of Alzheimer's disease
      and normal patients, both Lewy body dementia (7%) and cerebral infarcts
      contributing to dementia (6%) were frequent.

PMID- 7620531
TI  - Procedural memory and Parkinson's disease.
AB  - A detailed analysis of the mnestic deficits associated with Parkinson's disease
      (PD) contributes to explaining the cognitive disorders and their well documented
      consequences. This study was designed to show that, in PD declarative as well as
      procedural memory is severely impaired. Three tests designed to explore this
      aspect of mnestic functioning were proposed to a group of 16 parkinsonian
      patients whose motoricity was controlled: inverted reading, braille reading,
      sound form association. The results obtained, compared with those of young and
      aged controls, show that PD is associated with marked deficits in both
      declarative and procedural memory. Declarative memory impairment was similar to
      that observed in the control population (healthy elderly subjects, age-matched
      with the PD patients) but more marked in PD subjects. The procedural memory
      deficit was linked with age and pathology. Procedural memory involves a variety
      of processing modules dedicated to the type of information (visual, auditive,
      tactile codes). The deficits observed were more like a loss of automatism than
      procedural impairment stricto sensu ('knowing how'). It would be worth pursuing
      research by studying akinesia and motor disorders from the angle of automatic
      memory impairment.

PMID- 7620532
TI  - G. Paul Moore Lecture--1993. New voices for old.
AB  - Otolaryngology and voice science have entered the era of "phonosurgery." Several
      techniques allow voice professionals to intervene to restore or modify the voice
      in patients with immobile vocal folds and other problems related to voice
      production. It is necessary and appropriate that physicians and speech and
      language pathologists critically examine what has been accomplished and what may
      yet be possible for further voice improvement.

PMID- 7620533
TI  - The effect of voice lessons on the clinical and perceptual skills of graduate
      students in speech-language pathology.
AB  - Two groups of 10 speech-language pathology graduate students were each given 7
      weeks of singing lessons to determine whether voice lessons could have an effect
      on their clinical and perceptual skills. Pre-, mid-, and posttests to measure
      various skills were designed and implemented. With use of paired sample
      statistical testing, statistically significant results were obtained. In
      addition, the subjective responses of the students show that the lessons were
      effective in improving pitch perception, breath control, and legato production or
      easy onset. This study supports efforts to integrate curricula in vocal
      performance and speech-language pathology.

PMID- 7620534
TI  - Objective measures of voice production in normal subjects following prolonged
      voice use.
AB  - Laryngeal fatigue affects the physical sensations, effort, and perceptual quality
      of voice production. The underlying physiology of fatigue is not well understood.
      Acoustic, aerodynamic, and videostroboscopic data were measured in 10 normal
      speakers before and after prolonged voice use. Significant changes were found in
      the fundamental frequency of connected speech. Anterior glottal chinks were
      induced in a majority of subjects. Implications are discussed.

PMID- 7620535
TI  - Average speaking fundamental frequency in soprano singers with and without
      symptoms of vocal attrition.
AB  - Nineteen trained soprano singers aged 18-30 years vocalized tasks designed to
      assess average speaking fundamental frequency (SFF) during spontaneous speaking
      and reading. Vocal range and perceptual characteristics while singing with low
      intensity and high frequency were also assessed, and subjects completed a survey
      of vocal habits/symptoms. Recorded signals were digitized prior to being analyzed
      for SFF using the Kay Computerized Speech Lab program. Subjects were assigned to
      a normal voice or impaired voice group based on ratings of perceptual tasks and
      survey results. Data analysis showed group differences in mean SFF, no
      differences in vocal range, higher mean SFF values for reading than speaking, and
      58% ability to perceive speaking in low pitch. The role of speaking in too low
      pitch as causal for vocal symptoms and need for voice classification
      differentiation in vocal performance studies are discussed.

PMID- 7620536
TI  - Phonational profiles of male trained singers and nonsingers.
AB  - The purpose of this study was to compare the mean speaking fundamental frequency
      (SFF), speaking frequency range, and mean speaking intensity for a group of
      trained male singers and a group of age-matched non-singers in three age ranges:
      20 to 35 years old; 40 to 55 years old; and older than 65 years. Each subject was
      recorded as he read "The Rainbow Passage" and produced the vowel /a/ to the
      limits of his phonational frequency range. The data indicated that the mean SFF
      of the nonsingers was significantly lower among the middle-aged speakers than
      with the young or elderly. In contrast, the tenors exhibited no age-related SFF
      trends, and the young bass/baritones exhibited lower SFF levels than the middle
      aged or elderly. The elderly nonsingers produced frequency ranges that were
      smaller than any other group. Finally, the young nonsingers used greater speech
      intensity than did the other groups.

PMID- 7620537
TI  - A comparison of subglottal and intraoral pressure measurements during phonation.
AB  - Intraoral pressure and subglottal pressure, derived from tracheal puncture, were
      recorded with the electroglottographic signal for one normal speaking male during
      phonation. The mean subglottal pressure for vowels was also estimated by
      interpolating the intraoral pressure from surrounding /p/occlusions. The pressure
      measurements were highly correlated (r = 0.98) and there were small pressure
      value differences (on average < 2%). The effects of varying speech rate and mode
      of phonation on the pressure measurements are discussed. A decrease in pressure
      from the mean subglottal pressure for the open phase and an increase for the
      closed phase was found during the glottal vibratory cycles.

PMID- 7620538
TI  - Repeated measures of vocal fundamental frequency perturbation obtained using the
      Visi-Pitch.
AB  - This article reports on a study of intrasubject variability for a measure of
      vocal fundamental frequency perturbation in a group of young, normal speakers.
      Measurements of relative average perturbation (RAP) obtained using a Visi-Pitch
      were examined for the vowels /a/, /i/, and /u/ produced by 25 women and 24 men on
      two occasions, approximately 1 week apart. Important findings consisted of higher
      levels of RAP for women than men and greater variability of RAP over the time
      period studied for women than men. Conclusions include the need for additional
      normative data regarding the use of the Visi-Pitch for the purpose of examining
      jitter.

PMID- 7620539
TI  - Variation of electrolaryngographically derived closed quotient for trained and
      untrained adult female singers.
AB  - The derivation of larynx closed quotient (CQ) measures from the
      electrolarynogograph output is discussed and data are presented for a group of
      trained and untrained adult female singers (N = 26) for a sung two-octave G major
      scale. Statistically significant trends are observed between the trained and
      untrained groups that suggest for the trained group: (a) CQ tends to be lower for
      pitches below D4 and higher for pitches above B4, and (b) the gradient
      [CQ/log(F0)] tends to correlate positively with the number of years singing
      training/experience. These data are compared with those reported previously for
      an adult male group, and it is suggested that CQ could be a useful parameter to
      include in a real-time visual display for singing training.

PMID- 7620540
TI  - Vocal stability and vocal tract configuration: an acoustic and
      electroglottographic investigation.
AB  - Previous studies have reported differences in vocal fundamental frequency
      perturbation (jitter) and amplitude perturbation (shimmer) measures as a function
      of vowel type. However, it is not clear from those studies whether these effects
      derive from modifications in the shape of the vocal tract or from intrinsic vowel
      differences in mean fundamental frequency and vocal amplitude. The present study
      sought to address this issue using simultaneously obtained acoustic and
      electroglottographic (EGG) signals. Ten normal adult men and 10 normal adult
      women prolonged three maximally stable productions of the vowels [symbol: see
      text]. Vocal sound pressure level was maintained at 74 +/- 4 dB, while mean
      fundamental frequency was maintained at 110 and 220 Hz +/- 0.5 st for the male
      and female subjects, respectively. Results indicated that when vocal frequency
      and intensity are controlled, acoustic and EGG measures of mean jitter and
      shimmer do not show a significant vowel effect.

PMID- 7620541
TI  - Glottal closure, transglottal airflow, and voice quality in healthy middle-aged
      women.
AB  - Seventeen healthy women, 45 to 61 years old, were examined using
      videofiberstroboscopy during phonation at three loudness levels. Two
      phoniatricians evaluated glottal closure using category and ratio scales.
      Transglottal airflow was studied by inverse filtering of the oral airflow signal
      recorded in a flow mask (Glottal Enterprises System) during the spoken phrase
      /ba:pa:pa:pa:p/ at three loudness levels. Subglottal pressure was estimated from
      the intraoral pressure during p occlusion. Running speech and the repeated /pa:/
      syllables were perceptually evaluated by three speech pathologists regarding
      breathiness, hypo-, and hyperfunction, using continuous scales. Incomplete
      glottal closure was found in 35 of 46 phonations (76%). The degree of glottal
      closure increased significantly with raised loudness. Half of the women closed
      the glottis completely during loud phonation. Posterior glottal chink (PGC) was
      the most common gap configuration and was found in 28 of 46 phonations (61%). One
      third of the PGCs were in the cartilaginous glottis (PGCc) only. Two thirds
      extended into the membranous portion (PGCm); most of these occurred during soft
      phonation. Peak flow, peak-to-peak (AC) flow, and the maximum rate of change for
      the flow in the closing phase increased significantly with raised loudness.
      Minimum flow decreased significantly from normal to loud voice. Breathiness
      decreased with increased loudness. The results suggest that the incomplete
      closure patterns PGCc and PGCm during soft phonation ought primarily to be
      regarded as normal for Swedish women in this age group.

PMID- 7620542
TI  - Laryngeal mini-microflap: a new technique and reassessment of the microflap saga.
AB  - Vocal fold surgical technique has advanced substantially because of increased
      knowledge regarding anatomy and physiology of phonation and because of
      technological improvements. However, many new techniques have been based on
      anecdote and "common sense," largely because there is no good experimental model
      for vocal fold surgery since the human is the only species with a vocal ligament.
      Consequently, our earlier pronouncements require careful reexamination especially
      as new research adds to our fund of knowledge. Review of the principles and
      results of laryngeal microflap surgery suggests that there may be important
      shortcomings in the technique. A new mini-microflap technique appears better, as
      does limited mucosal resection. This is a preliminary report, and further
      investigation is needed.

PMID- 7620543
TI  - Gastroesophageal reflux laryngitis resistant to omeprazole therapy.
AB  - Gastroesophageal reflux disease (GERD) is known to cause a variety of symptoms
      that lead a patient to seek otolaryngologic care. New advances in the treatment
      of GERD have enabled otolaryngologists to eliminate most of the signs and
      symptoms caused by acid reflux. Omeprazole, the most recent pharmacologic
      advancement, has been reported to be universally successful in controlling acid
      release from the stomach of patients with GERD. This report describes a series of
      patients with GERD for whom high-dose omeprazole therapy was not successful in
      completely reducing gastric acid levels of GERD symptomatology.

PMID- 7620544
TI  - Introduction to the molecular biology of baculoviruses.

PMID- 7620545
TI  - Selection of recombinant baculoviruses by visual screening.

PMID- 7620546
TI  - Production of recombinant baculoviruses using linearized viral DNA.

PMID- 7620547
TI  - Rapid procedures for the isolation and PCR analysis of recombinant baculovirus.

PMID- 7620549
TI  - Fast isolation of recombinant baculovirus by antibody screening.

PMID- 7620548
TI  - Production of recombinant baculoviruses using rapid screening vectors that
      contain the gene for beta-galactosidase.

PMID- 7620550
TI  - Continuous foreign gene expression in transformed lepidopteran insect cells.

PMID- 7620551
TI  - Scale-up of recombinant virus and protein production in stirred-tank reactors.

PMID- 7620552
TI  - Expression of tissue inhibitor of metalloproteinases by recombinant baculovirus
      infected insect cells cultured in an airlift fermentor.

PMID- 7620553
TI  - Expression of foreign genes in Bombyx mori larvae using baculovirus vectors.

PMID- 7620554
TI  - Baculovirus transfer vectors.

PMID- 7620555
TI  - Expression of foreign proteins in Trichoplusia ni larvae.

PMID- 7620556
TI  - Use of baculoviruses as biological insecticides.

PMID- 7620557
TI  - Expression of the hemagglutinin protein of influenza virus. Analysis of protein
      modifications.

PMID- 7620558
TI  - Purification of the extracellular domain of the epidermal growth factor receptor
      produced by recombinant baculovirus-infected insect cells in a 10-L reactor.

PMID- 7620559
TI  - Comparison of different cell lines for the production of recombinant baculovirus
      proteins.

PMID- 7620560
TI  - Development of lepidopteran cell lines.

PMID- 7620561
TI  - Insect cell-culture techniques in serum-containing medium.

PMID- 7620562
TI  - Insect cell culture in serum-free media.

PMID- 7620563
TI  - Transfection techniques for producing recombinant baculoviruses.

PMID- 7620564
TI  - Host cell contaminant protein assay development for recombinant
      biopharmaceuticals.
AB  - The efficiency and consistency of a biopharmaceutical purification process
      determines drug quality, including which specific types and concentrations of
      residual host cell or process contaminants may remain. Commercial reagents and
      generic analytical methods are available for quantitating most of these
      contaminants. However, no generic assay is available for quantitation of the
      specific contaminant host cell proteins (HCPs) which are unique to a novel
      purification process. Because of this, proprietary reagents and assays must be
      developed for the quantitation of process-specific HCPs in each biopharmaceutical
      drug. The need to develop proprietary reagents which are both sensitive to, and
      specific for, potentially complex mixtures of unique contaminant proteins has
      defined what is acceptable methodology for development of quantitative HCP
      assays. Within the biopharmaceutical industry this need is most often satisfied
      by the development of multi-analyte HCP immunoassays based upon the null cell
      mock purification model. Confidence in the quantitative nature of a given HCP
      assay, and the validity of analytical measurement obtained by the assay, is
      dependent upon empirical demonstration of the unique stoichiometry of the HCP
      assay reagents. In conjunction with other analytical and validation methods, an
      HCP immunoassay may be thought of as a necessary quantitative tool for the
      optimization and validation of biopharmaceutical purification process efficiency
      and consistency, rather than as an end in itself.

PMID- 7620565
TI  - Moisture content in proteins: its effects and measurement.
AB  - Residual moisture content has a significant impact on the solid-state stability
      of biopharmaceutical products. Protein degradation due to residual moisture is
      minimal at or below the monolayer level of hydration owing to low availability of
      water and limited dynamic activity of the protein. However, residual moisture
      content beyond a monolayer generally results in increased rates of decomposition
      due to the enhanced conformational flexibility of the protein and the ability of
      the less tightly bound water to mobilize reactants. In addition to moisture
      content, the temperature and the composition of the lyophilized plug are
      important variables dictating the stability of proteins in the amorphous solid
      state. Water can act as a plasticizer to reduce the glass transition temperature,
      Tg, of the amorphous polymer, thus an increase in temperature or plasticizer
      level can result in a phase transition from a dynamically constrained state to a
      dynamically relaxed state. The selection of excipients can have a large impact on
      water-protein interactions as small ions and/or crystallization of excipients can
      redistribute water available to the protein. Owing to the key role that water
      content plays in the conformational and/or chemical state of the protein, an
      accurate and precise moisture determination is essential in resolving stability
      issues. A wide variety of techniques for the determination of moisture content
      have been utilized, with special attention being placed on sample handling to
      minimize atmospheric moisture contamination.

PMID- 7620566
TI  - Processing of C-terminal lysine and arginine residues of proteins isolated from
      mammalian cell culture.
AB  - C-terminal Lys or Arg residues whose presence was expected based on gene sequence
      information are often absent in proteins isolated from mammalian cell culture.
      This discrepancy is believed to be due to the activity of one or more basic
      carboxypeptidases. Internal Arg/Lys residues that become C-terminal upon
      proteolysis or zymogen activation, such as in the two-chain form of tissue
      plasminogen activator, may also be removed from the mature protein. Charge
      heterogeneity results when this type of processing is incomplete; such
      heterogeneity can be detected by isoelectric focusing or ion-exchange
      chromatography. The absence of C-terminal basic residues is not usually a
      regulatory concern, as plasma-derived proteins are often similarly processed.

PMID- 7620567
TI  - Capillary electrophoresis of S. nuclease mutants.
AB  - The electrophoretic migration behavior of 12 S. nuclease variants from
      Staphylococcus aureus with small but well defined structural differences from
      site directed mutation was investigated in free solution capillary
      electrophoresis at pH 2.8 to 9.5. The nucleases are basic proteins; the pI and
      the M(r) of the wild type are 10.3 and 16.811 kd, respectively. With specially
      selected oligoamino buffers and with an inert, hydrophilic wall coating in 75
      microns I.D. quartz capillary tubes, most of the proteins could be separated by
      CZE without interference by wall adsorption even at pH 9.5 where the selectivity
      was the highest. At pH 2.8, 4.1 and 7.0, S. nucleases are known to be in the
      random coil, "swollen" and the tight native state. Assuming that in a given
      state, i.e., at a certain pH, the molecular radii of the nucleases are the same,
      their hydrodynamic radii were calculated from their pertinent electrophoretic
      mobilities. The respective radii of 50.1, 26.8, and 25.0 Angstrum thus obtained
      agreed very well with the corresponding radii of gyration obtained from X-ray
      scattering. In fact, from the electrophoretic mobilities at pH 9.5, the existence
      of a hitherto unknown swollen basic state of the nuclease having a hydrodynamic
      radius of 30.5 Angstrum was postulated. In addition, a method was described to
      evaluate the valence of the protein at different pH from their pertinent
      electrophoretic mobilities. A general advantage of this method is that only the
      differences between the valences of the mutants and the wild type are needed; and
      for none of the proteins is required the knowledge of the actual valence. The
      results of the methods allowed the construction of a pH profile of the protein's
      valence. For the wild type, this profile was compared to the H+ titration curve
      and the agreement was excellent. Both methods employed some novel structure
      electrophoretic mobility relationships and the predicted protein properties
      compared remarkably well to the values obtained by exoelectrophoretic methods
      such as pH titration and X-ray scattering. Surprisingly, certain S. nucleases
      having the same valence could also be readily separated by CZE in some cases
      under the same conditions used for the others. Close examination of appropriate X
      ray crystallography and/or NMR data indicated subtle differences in the molecular
      structure of these proteins that could be responsible for slight alteration in
      their hydrodynamic radii.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7620568
TI  - Analysis of recombinant human growth hormone in Escherichia coli fermentation
      broth by micellar high-performance liquid chromatography.
AB  - A method for the reversed-phase high-performance liquid chromatographic (HPLC)
      determination of recombinant methionylaspartyl-human growth hormone (MD-HGH) in
      Escherichia coli fermentation broth is described. The technique utilizes mobile
      phases containing n-propanol and the anionic surfactant sodium dodecyl sulfate
      (SDS) under micellar conditions at pH 6.4. The methodology is directly applicable
      to the analysis of samples solubilized via sulfitolysis in the presence of SDS,
      and offers superior resolution in comparison with chromatography in the absence
      of the surfactant. Using this method, acceptable precision (day-to-day R.S.D. =
      4.9%), accuracy, selectivity, range, linearity and ruggedness were achieved.

PMID- 7620569
TI  - Detection of neu differentiation factor with a biospecific affinity sensor during
      chromatography.
AB  - A technique using a biospecific affinity sensor, BIAcore, was applied to monitor
      and determine mammalian cell-derived neu differentiation factor (NDF) in column
      fractions during chromatography. Specific purified polyclonal antibody against
      Escherichia coli-derived NDF was chemically bound to the surface of BIAcore
      sensor chips and the derivatized sensor chips were used to detect the specific
      binding of NDF. The measurement of NDF at very low levels can be assessed by
      injecting small volumes of the crude media or column fractions into the BIAcore
      sensor containing antibody-bound sensor chips. This automated procedure performed
      under computer programming control allows direct measurement of multiple NDF
      samples in a short period of time and provides excellent quantitative data, which
      is not possible using other related methods such as Western blotting, sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis and stimulatory activity assay
      on receptor autophosphorylation.

PMID- 7620570
TI  - Protein mass spectrometry: applications to analytical biotechnology.
AB  - The advent of matrix-assisted laser desorption/ionization mass spectrometry
      (MALDI-MS) and electrospray ionization mass spectrometry (ESI-MS) in the last 5
      years has greatly enhanced the area of protein mass spectrometry. This paper
      presents an overview of the applications of protein mass spectrometry in the area
      of analytical biotechnology, particularly as related to biopharmaceutical
      research and development. These applications include the determination of protein
      molecular mass, peptide mapping, peptide sequencing, ligand binding,
      determination of disulfide bonds, active site characterization of enzymes,
      protein self-association and protein folding/higher order structural
      characterization.

PMID- 7620571
TI  - High-speed high-performance liquid chromatography of peptides and proteins.
AB  - Over the last thirty years the name HPLC has been synonymous with high-speed
      liquid chromatography and during the last ten years we have experienced a
      dramatic increase in the speed of analysis particularly as far as the separation
      of biological macromolecules, such as proteins, is concerned. With a solid
      grounding in the chromatographic theories, column technology has been mainly
      responsible for the advances in this field. Recent development shows that columns
      packed with micropellicular or gigaporous stationary phases of the bidisperse or
      the bimodal type facilitate rapid mass transfer between the mobile and stationary
      phases and thus can deliver high resolution separations in a very short time.
      This suggest that HPLC has the potential to be the prime analytical technique for
      on-line monitoring of biotechnological processes in real time. Further
      enhancement of the speed of separation comes from the use of elevated
      temperatures. The role of temperature in HPLC has largely been ignored and most
      commercial instruments are not equipped with appropriate temperature control.
      Results presented here strongly suggest, however, that elevated column
      temperature may find increasing use in the HPLC of large molecules. In such
      analytical applications temperature programming may also play a major role
      provided columns with low heat capacity, such as packed fused-silica capillaries,
      gain wider employment in HPLC.

PMID- 7620572
TI  - Chemical methods of protein sequence analysis.

PMID- 7620573
TI  - Isoelectric focusing as a tool for the investigation of post-translational
      processing and chemical modifications of proteins.
AB  - It has been demonstrated that good agreement may be observed between computed and
      experimental isoelectric point (pI) values when proteins of known sequence are
      focused under denaturing conditions on immobilized pH gradient IPG slabs, at
      least in the pH range 4-7.5. Hence, discrepancies between expected and found in
      this experimental set-up may be reliably ascribed to some kind of post
      transcriptional processing, or chemical modification, having taken place in the
      sample. This evaluation is made easier when the comparison is set between the pI
      of a parent molecule and that (or those) of one to several of its derivatives as
      resolved in a single experiment (for instance, as a spot row in two-dimensional
      maps); no previous knowledge is required in these cases about the amino acid
      composition of the primary structure. The effects on protein surface charge are
      discussed in this review mainly for two biologically relevant processes,
      glycosylation and phosphorylation. Then, the pI shifts are analysed for some
      protein modifications that may occur naturally but can also be artefactually
      elicited, such as NH2 terminus blocking, deamidation and thiol redox reactions.
      Finally, carboxymethylation and carbamylation are used to exemplify chemical
      treatments often applied in connection with electrophoretic techniques and
      involving charged residues. Procedures to be applied in order to verify whether a
      given modification has occurred, and often relying on the focusing of a treated
      specimen, are detailed in each section. Numerical examples on model proteins are
      also discussed. As an important field of application of the above concepts may be
      genetic engineering, an exhaustive bibliographic list dealing with pI evaluation
      and structural assessment on recombinant proteins is included.

PMID- 7620575
TI  - Nutritional status of patients with endstage lung disease before and after lung
      transplantation.

PMID- 7620574
TI  - Fluorophore-assisted carbohydrate electrophoresis technology and applications.
AB  - Carbohydrates, in particular the complex carbohydrates conjugated to proteins and
      lipids, have important functions in a variety of biological systems. Their
      isolation and structural determination--prerequisites for elucidation of their
      biological functions--have been technical challenges for many decades. Almost all
      available chromatographic and electrophoretic methods as well as NMR and MS have
      been applied to carbohydrate analysis but none has proved satisfactory in terms
      of simplicity, sensitivity, reproducibility, cost and requirement for materials.
      Recently, a technique called fluorophore-assisted carbohydrate electrophoresis
      was developed which is very promising. It separates fluorescently-labeled
      carbohydrates on polyacrylamide gels and uses a charge-coupled device camera to
      detect and quantitate the products. This review describes the principles of the
      method and its applications to several aspects of research on carbohydrate
      containing biological biomolecules.

PMID- 7620576
TI  - RNS president's message: impending healthcare reform has stirred up a great deal
      of interest in the advanced practice nurse.

PMID- 7620577
TI  - Creative strategies in education: state-the-answer teams.

PMID- 7620578
TI  - An effective method of delivering albuterol.

PMID- 7620579
TI  - Eleanor Purrier.

PMID- 7620580
TI  - Seizure disorders.

PMID- 7620581
TI  - Withdrawal of antiepileptic drugs.
AB  - Recent literature on withdrawing antiepileptic drug therapy in patients who are
      seizure free on antiepileptic drugs is reviewed. The average recurrence risk
      across studies is 29% at 2 years. Factors such as age of onset, etiology of
      seizures, the electroencephalogram and the epileptic syndrome influence outcome.
      Factors that need to be considered by the clinician include not just the
      statistical risk of recurrence but also the consequences of a recurrence, which
      will be a function of age and sex.

PMID- 7620582
TI  - Epilepsy surgery in adults.
AB  - Epilepsy surgery is capable of stopping seizures or markedly reducing their
      frequency in selected patients with medically refractory epilepsy. Presurgical
      evaluation, as currently practiced, requires concordance among a battery of
      localizing tests. Cost-effectiveness is increasingly important in the development
      of optimal presurgical protocols and surgical procedures in specific patient
      populations.

PMID- 7620583
TI  - Epilepsy surgery in children.
AB  - The practice of operating on children with chronic epilepsy is rapidly gaining
      acceptance as an important therapeutic modality. This review summarizes some of
      the recent advances in pediatric epilepsy surgery in relation to the natural
      history of chronic childhood seizures, surgical treatment, and outcome. Candidate
      selection has been greatly facilitated by new information bearing on the natural
      history of medically resistant seizures and the greater than expected incidence
      of early hippocampal sclerosis. Because the majority of children suffer from
      extratemporal epilepsy, ictal single photon emission computed tomography and
      subdural electroencephalogram recording are becoming increasingly important for
      both seizure and functional localization in the child, and have been shown to be
      well tolerated, even in very young patients. Furthermore, the outcome of both
      excisional and commissural procedures in early life with respect to seizure
      control is similar to that reported for adults, irrespective of age. More
      information about the long-term effects of epilepsy surgery in children is
      urgently needed, but the available data confirms surgical therapy as an effective
      intervention with low morbidity.

PMID- 7620584
TI  - Pseudoseizures in the era of video-electroencephalogram monitoring.
AB  - Psychogenic seizures may be difficult to distinguish from epileptic seizures
      lacking electrographic correlate. The presence of concomitant epilepsy or
      Munchausen syndrome by proxy may increase diagnostic difficulty. Clinical seizure
      characteristic, suggestion, prolactin levels, and continued recording after
      medication withdrawal may be useful in reaching a diagnosis. Dissociative
      disorders may be very common in psychogenic seizure patients.

PMID- 7620585
TI  - Models of primary generalized epilepsy.
AB  - The most important recent development in primary generalized epilepsy has been
      the use of in-vitro and in-vivo models to delineate the neuronal populations and
      intrinsic mechanisms, which generate the synchronized thalamocortical burst
      firing of absence seizures. Candidate molecular mechanisms, which may be
      critically involved in the pathogenesis of absence seizures in selected animal
      models, include the following: altered biophysical properties of T-type calcium
      channels in the genetic absence epilepsy rat of Strasbourg (GAERS) model;
      increased numbers of gamma-aminobutyric acid, B subtype receptors in the
      lethargic mouse (lh/lh mouse) model; and changes in the subunit composition of
      gamma-aminobutyric acid, A subtype receptors in the GAERS model. Regarding
      generalized convulsive seizures, neuronal populations within the inferior and
      superior colliculi appear to regulate seizures in the genetic epilepsy-prone rat
      (GEPR) model, and subpopulations within the substantia nigra pars reticulata
      (SNR) appear to regulate seizures in the fluorothyl model. Deficiencies in the
      function of GABAergic and noradrenergic receptors may underlie generalized
      convulsive seizures in the GEPR model.

PMID- 7620586
TI  - Genetics of the epilepsies.
AB  - The epilepsy gene map has been refined and extended with new information
      concerning benign familial neonatal convulsions, benign familial infantile
      convulsions, Unverricht-Lundborg disease, epilepsy with progressive mental
      retardation and juvenile myoclonic epilepsy. Understanding of the molecular basis
      of paroxysmal disorders affecting the central nervous system has been
      revolutionalized with the identification of mutations in genes for the
      neurotransmitter receptors, GLRA1 and CHRNA4, and a voltage-gated potassium
      channel, KCNA1, as causes of inherited neurological disease.

PMID- 7620587
TI  - Quantitative magnetic resonance imaging in autism: the cerebellar vermis.
AB  - Two recent magnetic resonance imaging studies, including a retrospective analysis
      of apparently 'contradictory' data from other investigators, appear to confirm
      earlier reports of vermal hypoplasia in autism. However, a review of the
      methodology used in these two studies suggests that definitive conclusions
      concerning cerebellar vermal pathology in autism are still premature.

PMID- 7620588
TI  - Infantile spasms.
AB  - The recent intense focus of attention on further characterization and management
      of infantile spasms is due, in part, to the resistant nature of these seizures
      and the frequently poor cognitive outcome, even when the seizures are controlled.
      Technological advances have increased our ability to diagnose specific brain
      disorders associated with infantile spasms, and have led to new therapeutic
      approaches. Most infantile spasms previously classified as cryptogenic have now
      been shown to be associated with various types of brain malformations and can,
      therefore, be reclassified as symptomatic. Infantile spasms are probably
      initiated by cortical epileptic discharges which propagate to the brainstem and
      other subcortical areas. When the epileptogenic cortex is unilateral in an infant
      with resistant spasms, resective surgery may be considered. For most infants,
      however, surgery is not a viable option, and the search for the most effective
      and least toxic anticonvulsant continues.

PMID- 7620589
TI  - Magnetic resonance spectroscopy in neonates.
AB  - Magnetic resonance spectroscopy allows noninvasive assessment of cerebral
      metabolism in newborn infants. 31P magnetic resonance spectroscopy has
      demonstrated that birth asphyxia leads to delayed impairment of cerebral energy
      metabolism and 1H magnetic resonance spectroscopy has shown lactate accumulation
      and a later decline in N-acetyl aspartate concentration. 13C magnetic resonance
      spectroscopy may help explain these observations.

PMID- 7620590
TI  - Central nervous system infections in children (bacterial, tubercular).
AB  - Central nervous system infections are an important cause of childhood morbidity
      and mortality. This review discusses recent developments in diagnostic tests,
      management strategies, and prevention of bacterial and tubercular meningitis.

PMID- 7620591
TI  - Rett syndrome.
AB  - Rett syndrome is a unique and puzzling disorder noted in females, and is possibly
      caused by fundamental failures in critical brain connectivity during early
      infancy. Recent reports expand our understanding of the Rett syndrome phenotype,
      continue the pattern of inconsistent or inconclusive metabolic and genetic
      results, and extend observations regarding abnormal brain cytoarchitecture.

PMID- 7620592
TI  - Integrated use of old and new antiepileptic drugs.
AB  - Three new antiepileptic drugs have been approved for use in the USA in the past
      year and a half and several others are available in Europe and Japan. Each of
      these drugs has been efficacious against partial seizures without or with
      secondary generalization and some may also be efficacious against primary
      generalized seizures. None of the new drugs appears to be a quantum leap in
      therapy over the others that are already available. How these new drugs will be
      integrated into a rational scheme for the treatment of individuals with epilepsy
      remains to be determined. Side-effect profiles, pharmacokinetic issues, and cost
      will likely be significantly issues.

PMID- 7620593
TI  - Physician suicide.

PMID- 7620594
TI  - Advanced practice nurses: should they be independent?

PMID- 7620595
TI  - Pharmacoeconomic considerations in pharmaceutical company promotions.

PMID- 7620596
TI  - Health professional shortage areas, health status, and reform.

PMID- 7620597
TI  - The relationship of health professional shortage areas to health status.
      Implications for health manpower policy.
AB  - OBJECTIVE: To compare the health status of adult residents of health professional
      shortage areas (HPSAs) with adult residents of non-HPSAs. DESIGN: A random-digit
      dialing telephone survey. Respondents were subsequently classified by their
      county of residence as residing in an HPSA or non-HPSA. PARTICIPANTS: A sample of
      470 adults (18 years or older) living in Kentucky. MAIN OUTCOME MEASURES: Health
      status was measured by the Medical Outcomes Study 20-Item Short-Form Health
      Survey's six subscales. RESULTS: Controlling for demographic variables in the
      multiple regression analysis, there were significant differences between HPSAs
      and non-HPSAs for the social, mental health, and pain subscales. An interaction
      between age and HPSAs in relation to health status was observed for the physical,
      social, mental health, health perception, and pain subscales. After
      stratification by age (18 to 44 years, 45 to 64 years, or 65 years or older),
      HPSA-designated areas were associated with poorer health status in all but the
      youngest age strata. Elders in HPSAs had the poorest health status. CONCLUSIONS:
      Health professional shortage areas are associated with poorer health status in
      the older segments of the adult population. Future policy may need to focus on
      increasing access not only to primary care services but also to specific types of
      services that may promote better health status of elderly residents of HPSAs.

PMID- 7620598
TI  - Physician patterns in the provision of health care to their own employees.
AB  - OBJECTIVE: To determine the level of medical and mental health care that family
      physicians provide to employees. DESIGN: Mailed survey. SETTING: Family practices
      in Oklahoma. SUBJECTS: Two hundred ninety-one of 735 physicians assessed via the
      membership roster of the Oklahoma Academy of Family Physicians. RESULTS: The
      majority of physician respondents (55.6%) reported providing routine health care
      always or most of the time to employees. Rural practice sites were associated
      with the provision of broader medical services (Spearman's p = -.35, P < .00001);
      51.7% of respondents reported providing routine health care always or most of the
      time to employees' families. Breast and genital examinations were more likely to
      be undertaken in family members (67.2%) compared with employees (50.0%). Only a
      minority of physician respondents (12.3%) reported providing mental health care
      always or most of the time to employees; 53% never or rarely provided this
      service. When mental health care was addressed, respondents provided counseling
      alone (28.6%), prescription of psychotropic medication alone (8.8%), or both
      (62.7%). Antidepressants (50.7%) and nonbenzodiazepine anxiolytic agents (36.2%)
      were most frequently prescribed. When asked about ideal conditions, a significant
      minority of physician respondents (41.3%) preferred to refer employees to
      colleagues for medical care, and 59.8% preferred to refer for mental health care.
      CONCLUSION: The majority of family physicians in this study reported providing
      medical care to their employees, whereas only a minority provide mental health
      care.

PMID- 7620599
TI  - Clinical use of ambulatory blood pressure monitoring. A review of value in
      patient care.
AB  - OBJECTIVE: To examine the value of ambulatory blood pressure monitoring in
      routine clinical use. DESIGN: We retrospectively reviewed 350 determinations made
      over a 4-year period. SETTING AND PATIENTS: A practice-based sample of patients
      attending the Hypertension Outpatient Clinic. RESULTS: Successful records were
      obtained in 346 of these procedures and night/sleep recordings were accomplished
      in 320. Monitor readings compared satisfactorily with auscultatory
      determinations. Declines in systolic and diastolic blood pressure during
      night/sleep of 8.2% and 13.2%, respectively, and a fall in the heart rate of
      12.0% were noted; these declines were significantly lesser in patients with
      diabetes. Age, gender, therapy, and 24-hour average blood pressures, however, had
      minimal relationship to the night/sleep declines in blood pressure and heart
      rate. CONCLUSIONS: Twenty-four-hour blood pressure monitoring is acceptable to
      patients. Night/sleep declines in blood pressure are blunted in diabetics.

PMID- 7620600
TI  - Computerized patient records in primary care. Their role in mediating guideline
      driven physician behavior change.
AB  - Implementation of practice guidelines remains problematic in spite of enormous
      efforts to develop and disseminate them, to establish their credibility, and to
      create incentives for physicians to adopt them. These strategies have failed to
      systematically change physician behavior because they do not address the
      involuntary time and mental processing constraints that have been clearly
      demonstrated to hamper physicians' ability to comply with guidelines.
      Computerized patient record systems directly address these constraints, and
      evidence is mounting that they are effective tools for changing physician
      behavior. A properly configured computerized patient record system provides
      decision support, facilitates work flow, and enables the routine collection of
      data for performance feedback. A synthesis of relevant research from the domains
      of practice guidelines and medical informatics strongly suggests that the
      operational support provided by computerized patient record systems will have a
      major impact on physician compliance with practice guidelines.

PMID- 7620601
TI  - Nutritional factors and hypertension.
AB  - Hypertension is a major risk factor for coronary artery disease, stroke, renal
      failure, and peripheral vascular disease. The importance of preventing
      hypertension and controlling blood pressure in patients with hypertension is well
      established and is associated with reduced cardiovascular morbidity and mortality
      rates. Treatment guidelines should consider the merits of dietary changes in
      addition to pharmacologic therapy in the control of mild hypertension.

PMID- 7620602
TI  - Colonic medication bezoar from extended-release nifedipine and procainamide.
AB  - We report an unusual case of a primary colonic bezoar composed of extended
      release formulations of nifedipine and procainamide. Although these bezoars are
      rare, the increasingly frequent application of extended-release delivery systems
      to other commonly prescribed medications may increase the incidence of such
      bezoars in vulnerable patients. Clinicians should be aware of this potential
      problem when prescribing these medications, and have a high index of suspicion
      when painful or refractory constipation occurs.

PMID- 7620603
TI  - Hypermagnesemia. Elderly over-the-counter drug users at risk.
AB  - We present a case of magnesium toxic effects that demonstrates the wide spectrum
      of associated clinical signs and symptoms. As shown by the case report, the
      literature review, and the MEDWATCH database, physicians frequently neglect to
      consider hypermagnesemia in the differential diagnosis of this clinical
      presentation. Abnormal renal function is a well-known risk factor for the
      development of hypermagnesemia. This case report highlights several associated
      nonrenal risk factors for hypermagnesemia, which include age, gastrointestinal
      tract disease, and administration of concomitant medications, particularly those
      with anticholinergic and narcotic effects. This case report also demonstrates how
      consumers may misuse magnesium-containing over-the-counter drug products. In
      addition, physicians may not inquire about and patients may not volunteer over
      the-counter medications in a complete drug history. However, the morbidity
      associated with hypermagnesemia as well as its reversibility make it an important
      diagnostic consideration for elderly patients with gastrointestinal tract
      disease, regardless of renal function. For easy reference for both consumers and
      health-care personnel, we provide a list of over-the-counter drug products that
      contain significant amounts of magnesium.

PMID- 7620604
TI  - Serotonin modulation of inferior olivary oscillations and synchronicity: a
      multiple-electrode study in the rat cerebellum.
AB  - Simultaneous recording of complex spikes from multiple Purkinje cells (up to 44)
      in the rat cerebellum was used to examine the effects of 5-hydroxytryptamine
      (serotonin, 5-HT) on olivocerebellar function. Microinjection into the inferior
      olive was found to increase the average firing rate of inferior olivary neurons
      while slowing their oscillation frequency and increasing the coherence of their
      oscillations. Indeed, while the normal rostrocaudal band of synchronous activity
      remained unchanged, the degree of synchrony between Purkinje cell complex spikes
      within this band was enhanced following the 5-HT injections. Multiple-electrode
      recordings obtained from crus Ila and vermal lobule Vlb yielded qualitatively
      similar results; however, the effects on vermal activity were more pronounced.
      The effects of the 5-HT microinjection decayed with a time course of 75 min. The
      half-maximum effective concentration of 5-HT was between 10 and 100 microM.
      Injections of various 5-HT agonists and antagonists demonstrated that a 5-HT type
      2A (5-HT2A) receptor is the main mediator for the 5-HT effect, which was very
      similar to the effect produced by injections of harmaline. However, 5-HT and
      harmaline appear to have independent mechanisms since the action of harmaline was
      not blocked by the 5-HT2A antagonist LY53857. A possible role for 5-HT, as a
      physiological enhancer of the timing of motor function of the olivocerebellar
      system, is discussed.

PMID- 7620605
TI  - Distinct temporal patterns of expression of sodium channel-like immunoreactivity
      during the prenatal development of the monkey and cat retina.
AB  - Polyclonal and monoclonal antibodies prepared against the alpha-subunit of the
      voltage-gated sodium channel (alpha NaCh) were used to examine the distribution
      of sodium channel-like immunoreactivity during the prenatal development of the
      cat and rhesus monkey (Macaca mulatta) retina. At all prenatal ages studied,
      beginning on embryonic day 29 (E29) in the cat and E52 in the monkey, both
      antibodies labelled optic axons. With the polyclonal antibodies, the appearance
      of positive cells largely mirrored the onset of their morphological maturation.
      Immunoreactivity appeared first in the somata of ganglion cells, and subsequently
      the inner plexiform layer could be distinguished by its intense immunolabelling.
      A few weeks later horizontal cells displayed immunolabelling that extended to
      their dendrites in the developing outer plexiform layer. This was followed by
      immunoreactive cones, with bipolar cells labelled only postnatally. By contrast,
      with the monoclonal antibody some cells were found to be immunoreactive while
      their somata were still in the ventricular layer (E33 in cat and E52 in monkey).
      Many of these cells appeared to migrate to the outer portion of the prospective
      inner nuclear layer, where they gradually acquired the morphological appearance
      of bipolar cells. Transient expression of immunolabelling with monoclonal sodium
      channel antibody was found in the cones of the cat and cones and rods of the
      monkey. These results indicate that different types of alpha NaCh-like proteins
      are expressed in the mammalian retina at distinct developmental periods. Their
      presence at very early stages during development suggests that these proteins
      could play a specific role in the commitment and/or differentiation of specific
      retinal cell types.

PMID- 7620606
TI  - Distribution of a brain-specific proteoglycan, neurocan, and the corresponding
      mRNA during the formation of barrels in the rat somatosensory cortex.
AB  - Neurocan is a developmentally regulated chondroitin sulphate proteoglycan in the
      rat brain. In the present study, spatiotemporal patterns of expression of
      neurocan and the corresponding mRNA were examined in the developing cortical
      barrel field of the rat brain by using a monoclonal antibody that was highly
      specific to neurocan and a riboprobe for a portion of the mRNA.
      Immunohistochemical analysis revealed that neurocan was distributed throughout
      the cerebral cortex during early postnatal development but was excluded from the
      centres of cortical barrels at the time of entry and arborization of
      thalamocortical axons. At this developmental stage, expression of neurocan mRNA
      was shown by in situ hybridization to be down-regulated in the barrel centres.
      When a row of whisker follicles was laser-cauterized on postnatal day 1, the
      pattern of expression of neurocan was disturbed in the row of barrels that
      corresponded to the lesioned whisker follicles in the contralateral somatosensory
      cortex. From these observations, it appears that neuronal stimuli through early
      thalamocortical fibres from the sensory periphery cause reduced expression of
      neurocan mRNA in neurocan-producing cells in the presumptive barrel centres. Our
      findings also suggest that the pattern of distribution of neurocan in early
      postnatal barrel fields may be due mainly to the down-regulation of expression of
      neurocan mRNA.

PMID- 7620607
TI  - Dopaminergic agonists have both presynaptic and postsynaptic effects on the
      guinea-pig's medial vestibular nucleus neurons.
AB  - A number of studies have indicated a possible interaction between dopamine and
      the vestibular system. Using intracellular recordings in brainstem slices, we
      have tested the effects of dopamine and other dopaminergic compounds on guinea
      pig medial vestibular nucleus (MVN) neurons. In normal medium, MVN neurons were
      depolarized by dopamine as well as by (-)quinpirole and piribedil, which are
      selective D2 dopaminergic agonists. The dependence of this effect on the presence
      of D2 receptors was confirmed by using (-)sulpiride, a D2 antagonist which
      blocked the depolarizing effect of dopamine. Dopaminergic D1 receptors were
      apparently not involved in this effect since a selective D1 agonist, SKF-38393,
      had no effect on MVN neurons and the D1 antagonist (+)SCH-23390 could not block
      the effect of dopamine. These depolarizing responses to dopamine must be due to a
      presynaptic action on terminals that normally release GABA spontaneously on MVN
      neurons, and tonically maintain them in a state of hyperpolarization. Indeed,
      such a spontaneous release was demonstrated to occur in the slice since
      application of bicuculline, a GABAA antagonist, depolarized MVN neurons in normal
      saline, but not in a high Mg2+/low Ca2+ solution known to block synaptic
      transmission. When dopamine was applied in conditions in which no GABAA-dependent
      transmission could occur (either in the presence of bicuculline or in a high
      Mg2+/low Ca2+ solution) only a hyperpolarizing, most probably postsynaptic,
      effect occurred. These results indicate that dopamine might exert in vivo a
      significant modulatory action on the vestibular system, either by a direct action
      on the vestibular neurons or by modulation of GABAergic transmission.

PMID- 7620608
TI  - MK-801 blockade of Fos and Jun expression following passive avoidance training in
      the chick.
AB  - Training chicks on a one-trial passive avoidance task results in transient up
      regulation of the N-methyl-D-aspartate (NMDA) receptor in the left intermediate
      medial hyperstriatum ventrale (IMHV) of the forebrain 30 min post-training.
      Injection of the non-competitive NMDA receptor inhibitor, (+)-5-methyl-10,11
      dihydro-5H-dibenzo(a,d)-cyclohepten 5,10-imine maleate (MK-801), around the time
      of training renders chicks amnesic for the task. Training also results in
      enhanced expression of the immediate early gene (IEG) c-fos in the IMHV. To
      determine the relationship between NMDA receptor up-regulation and IEG induction
      during memory formation we have examined the expression of Fos, Jun and their
      related proteins 2 h following training in the presence/absence of the putative
      amnestic agent MK-801. Western blotting of IMHV samples revealed two protein
      bands with immunoreactivity to the Fos antibody at 47 and 54 kDa. Using an
      antibody to Jun, two immunoreactive bands were revealed at 39 and 54 kDa. All
      bands were enhanced in the left IMHV following passive avoidance training. Post
      training intraperitoneal injections of MK-801 (75 mM) produced amnesia in
      approximately 50% of the birds when tested 1 h after training. Injection of MK
      801 significantly attenuated expression of these proteins in birds rendered
      amnesic, but not in those that recalled the task. We conclude that NMDA receptor
      activation precedes immediate early gene expression in the memory formation
      cascade.

PMID- 7620609
TI  - Auditory cortex of the rufous horseshoe bat: 1. Physiological response properties
      to acoustic stimuli and vocalizations and the topographical distribution of
      neurons.
AB  - The extent and functional subdivisions of the auditory cortex in the echolocating
      horseshoe bat, Rhinolophus rouxi, were neurophysiologically investigated and
      compared to neuroarchitectural boundaries and projection fields from connectional
      investigations. The primary auditory field shows clear tonotopic organization
      with best frequencies increasing in the caudorostral direction. The frequencies
      near the bat's resting frequency are largely over-represented, occupying six to
      12 times more neural space per kHz than in the lower frequency range. Adjacent to
      the rostral high-frequency portion of the primary cortical field, a second
      tonotopically organized field extends dorsally with decreasing best frequencies.
      Because of the reversed tonotopic gradient and the consistent responses of the
      neurons, the field is comparable to the anterior auditory field in other mammals.
      A third tonotopic trend for medium and low best frequencies is found dorsal to
      the caudal primary field. This area is considered to correspond to the
      dorsoposterior field in other mammals. Cortical neurons had different response
      properties and often preferences for distinct stimulus types. Narrowly tuned
      neurons (Q10dB > 20) were found in the rostral portion of the primary field, the
      anterior auditory field and in the posterior dorsal field. Neurons with double
      peaked tuning curves were absent in the primary area, but occurred throughout the
      dorsal fields. Vocalization elicited most effectively neurons in the anterior
      auditory field. Exclusive response to pure tones was found in neurons of the
      rostral dorsal field. Neurons preferring sinusoidal frequency modulations were
      located in the primary field and the anterior and posterior dorsal fields
      adjacent to the primary area. Linear frequency modulations optimally activated
      only neurons of the dorsal part of the dorsal field. Noise-selective neurons were
      found in the dorsal fields bordering the primary area and the extreme caudal edge
      of the primary field. The data provide a survey of the functional organization of
      the horseshoe bat's auditory cortex in real coordinates with the support of
      cytoarchitectural boundaries and connectional data.

PMID- 7620611
TI  - The corticotectal projection of the rat in vitro: development, anatomy and
      physiological characteristics.
AB  - In this study, the formation of the corticotectal projection of the rat in
      organotypic slice culture was investigated, using both anatomical and
      physiological approaches. The establishment of fibre connections from visual
      cortex to superior colliculus explants was monitored after 3, 6, 14, 20 and 30
      days in vitro by cortical injections of Dil. As in cortical cultures without
      cocultured colliculus, fibres anterogradely labelled by this procedure spread
      radially from the injection site into the surroundings of the explant, without
      displaying any directional preference. Especially, layer V pyramidal cells could
      be seen to extend processes not only to the collicular target, but also in the
      opposite direction, suggesting that no axonal guidance was exerted by the
      projection target. The total number of fibres projecting in the direction of the
      colliculus was not higher than of those projecting in the opposite direction.
      However, fibres projecting into the colliculus were significantly longer. This
      was also the case when the colliculus was placed next to the pial side of the
      cortical explant, indicating that outgrowth direction was not related to this
      observation. We therefore assume a chemotrophic rather than a chemotactic
      influence of the projection target on cortical axons, which is based on direct
      contact of axons to the target tissue. It cannot be excluded, however, that the
      failure to detect chemotactic guidance was caused by the lack of diffusion
      gradients in our culture system. Innervation of the collicular slice exclusively
      originated from layer V pyramidal cells, irrespective of the position of the
      collicular target. Fibre courses suggested that discrimination of the projection
      target was achieved upon encounter with the collicular surface by direct membrane
      contact. Inside the collicular tissue, fibre arborizations occurred preferredly
      in up to three layers perpendicular to the surface. Even after the smallest
      tracer injections, termination fields were diffusely distributed over the
      collicular slice. Also, the spatial distribution of retrogradely stained
      projection neurons did not differ statistically from an equal distribution. Thus,
      a high degree of convergence and divergence was observed anatomically in the
      corticotectal projection formed in vitro, corresponding to the immature state in
      vivo. The functionality of the corticotectal projection was assessed by
      intracellular recordings from collicular neurons. Electrophysiological
      properties, such as membrane potential (-68 +/- 11 mV), membrane resistance (35.4
      +/- 27.7 M omega) and the time constant (3.0 +/- 2.1 ms) were comparable to
      reference values, confirming the viability of our culture preparation. The
      functionality of corticotectal transmission was revealed by intracellularly
      recorded responses of collicular cells to extracellular cortical
      stimulation.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7620610
TI  - Interleukin-1 beta stimulates both central and peripheral release of vasopressin
      and oxytocin in the rat.
AB  - Simultaneous microdialysis in the brain and blood was used to monitor the release
      of vasopressin and oxytocin within the hypothalamic supraoptic (SON) and
      paraventricular (PVN) nuclei and into the systemic circulation of urethane
      anaesthetized male rats before and after central administration of interleukin-1
      beta (IL-1 beta). Following intracerebroventricular infusion of the cytokine (200
      ng/5 microliters), the content of vasopressin (up to 278% compared to vehicle
      treated control, P < 0.01 compared to vehicle-treated control and preinfusion
      baseline) but not oxytocin (up to 148%, not significant) in 30-min blood
      microdialysates was found to be increased. This peripheral release was
      accompanied by a transient rise in vasopressin (up to 163%, P < 0.05) and
      oxytocin (up to 182%, P < 0.05) release within the SON, the peak typically
      occurring during the first and second 30-min collection intervals after IL-1 beta
      respectively. In contrast, in the simultaneously microdialysed PVN, both
      vasopressin and oxytocin failed to respond to intracerebroventricular IL-1 beta.
      In another series of experiments, IL-1 beta was directly infused (20 ng/0.5
      microliters) into either the SON or PVN during microdialysis of the corresponding
      nucleus. The cytokine caused a significant and immediate rise in intra-SON
      release of both vasopressin (up to 225%, P < 0.01) and oxytocin (up to 178%, P <
      0.05). Again, in the PVN, nonapeptide release, although tending to be stimulated
      in response to intranuclear IL-1 beta, failed to reach statistical significance.
      The cytokine-induced central and peripheral release pattern appeared to be
      independent of the rise in body temperature observed after IL-1 beta
      administration.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7620612
TI  - Chondroitin sulphate proteoglycans in the rat brain: candidates for axon barriers
      of sensory neurons and the possible modification by laminin of their actions.
AB  - The addition of chondroitin sulphate proteoglycans (CSPGs), purified from the rat
      brain, to the culture medium of PC12D cells inhibited their proliferation and
      neurite outgrowth. Therefore, we investigated the effects of several
      extracellular components on the inhibitory actions of CSPGs on PC12D cells, as
      well as their immunocytochemical distribution in the rat embryo to determine
      whether the findings in vitro could be reproduced in vivo. Coating of the
      substratum with polylysine was necessary for the appearance of the inhibitory
      effects of brain CSPGs on PC12D cells. The additional pretreatment of polylysine
      coated dishes with laminin or fibronectin promoted the outgrowth of neurites from
      PC12D cells. Laminin and fibronectin, but not collagen (types I and IV) and CELL
      TAK (cell adhesion molecules), prevented the inhibitory effects of brain CSPGs in
      a concentration-dependent manner. Doses producing 50% reduction by laminin (or
      fibronectin) of the CSPG effects were 1.5 (or 25) micrograms/ml for neurite
      outgrowth and 2.2 (or 28) micrograms/ml for proliferation. The ratio of dish
      attached CSPGs to laminin necessary for 50% reduction was about approximately
      50:1 (wt/wt). Laminin from any source had the same effect. Brain CSPGs also
      obviously impeded the growth of fibres from dorsal root ganglion explants and
      primary cultured dorsal root ganglion neurons. Neurocan (a major CSPG in the
      brain)-like immunoreactivity was detected in the boundary caps and roof plate in
      the rat embryo at 13.5 days of gestation, when DRG neurons were extending their
      axons to the neural tube. The distributions of laminin and tenascin appeared,
      respectively, to be slightly and considerably different from that of
      neurocan.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7620613
TI  - Molecular cloning, functional expression and pharmacological characterization of
      the human metabotropic glutamate receptor type 2.
AB  - A cDNA encoding the human metabotropic glutamate receptor type 2 (hmGluR2) was
      isolated from human brain cDNA libraries by cross-hybridization with rat mGluR2
      probes. The deduced amino acid sequence of the human mGluR2 receptor consists of
      872 residues and shows a sequence identity of 97% to the amino acid sequence of
      rat mGluR2. Northern blot analyses showed that hmGluR2 is widely expressed in
      different regions of the adult brain as well as in fetal human brain. Genomic
      Southern blotting localized the mGluR2 gene to human chromosome 3. Chinese
      hamster ovary (CHO) cells stably transfected with the cloned hmGluR2 cDNA exhibit
      agonist induced depression of forskolin-stimulated cAMP accumulation. A direct
      comparison of CHO cells stably expressing human and rat mGluR2 with five agonists
      revealed the same rank order of potency [(2S,3S,4S)-alpha-(carboxycyclopropyl)
      glycine >> (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid = L-glutamate >>
      quisqualate = L-2-amino-4-phosphonobutyric acid] and similar EC50 values for both
      homologous receptors. (R,S)-alpha-methyl-4-carboxyphenylglycine, a reported
      antagonist at some mGluR subtypes, reduced the depression of forskolin-induced
      cAMP accumulation by (1S,3R)-ACPD in both human and rat mGluR2.

PMID- 7620614
TI  - Immunocytochemical localization of the alpha 1 and beta 2/3 subunits of the GABAA
      receptor in relation to specific GABAergic synapses in the dentate gyrus.
AB  - Dentate granule cells receive spatially segregated GABAergic innervation from at
      least five types of local circuit neurons, and express mRNA for at least 11
      subunits of the GABAA receptor. At most two to four different subunits are
      required to make a functional pentamer, raising the possibility that cells have
      on their surface several types of GABAA receptor channel, which may not be
      uniformly distributed. In order to establish the subcellular location of GABAA
      receptors on different parts of dentate neurons, the distribution of
      immunoreactivity for the alpha 1 and beta 2/3 subunits of the receptor was
      studied using high-resolution immunocytochemistry. Light microscopic
      immunoperoxidase reactions revealed strong GABAA receptor immunoreactivity in the
      molecular layer of the dentate gyrus. Pre-embedding immunogold localization of
      the alpha 1 and beta 2/3 subunits consistently showed extrasynaptic location of
      the GABAA receptor on the somatic, dendritic and axon initial segment membrane of
      granule cells, but failed to show receptors in synaptic junctions. Using a
      postembedding immunogold technique on freeze-substituted, Lowicryl-embedded
      tissue, synaptic enrichment of immunoreactivity for these subunits was found on
      both granule and non-principal cells. Only the postembedding immunogold method is
      suitable for revealing relative differences in receptor density at the
      subcellular level, giving approximately 20 nm resolution. The immunolabelling for
      GABAA receptor occupied the whole width of synaptic junctions, with a sharp
      decrease in labelling at the edge of the synaptic membrane specialization. Both
      subunits have been localized in the synaptic junctions between basket cell
      terminals and somata, and between axo-axonic cell terminals and axon initial
      segments of granule cells, with no qualitative difference in labelling. Receptor
      immunopositive synapses were found at all depths of the molecular layer. Some of
      the boutons forming these dendritic synapses have been shown to contain GABA,
      providing evidence that some of the GABAergic cells that terminate only on the
      dendrites of granule cells also act through GABAA receptors. Double
      immunolabelling experiments demonstrated that a population of GABA-immunopositive
      neurons expresses a higher density of immunoreactive GABAA receptor on their
      surface than principal cells. Interneurons were found to receive GABAA receptor
      positive synapses on their dendrites in the hilus, molecular and granule cell
      layers. Receptor-immunopositive synapses were also present throughout the hilus
      on presumed mossy cells. The results demonstrate that both granule cells and
      interneurons exhibit a compartmentalized distribution of the GABAA receptor on
      their surface, the postjunctional membrane to GABAergic terminals having the
      highest concentration of receptor.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7620616
TI  - Synergistic trophic actions on rat basal forebrain neurons revealed by a
      synthetic NGF/BDNF chimaeric molecule.
AB  - Basal forebrain cholinergic neurons, which degenerate in Alzheimer's disease,
      respond to multiple trophic factors, including the neurotrophins, nerve growth
      factor (NGF) and brain-derived neurotrophic factor (BDNF). This dual
      responsiveness prompted us to investigate the effects of a synthetic chimaeric
      molecule, containing the active domains of both NGF and BDNF. The NGF/BDNF
      chimaeric factor exhibited synergistic actions, and was 100-fold more potent than
      wild-type BDNF in enhancing survival of cultured dissociated basal forebrain
      cholinergic neurons. This effect was apparently due to true BDNF/NGF synergy,
      since addition of the two wild-type trophins simultaneously reproduced the effect
      of the chimaera. Synergy was selective for neurons which respond to both factors;
      substantia nigra dopaminergic neurons, which respond to BDNF but not NGF,
      exhibited no potentiation. The chimaeric factor thus revealed a synergy that may
      normally occur in the brain, and constitutes a potentially novel therapeutic
      agent with greater potency than naturally occurring individual trophins.

PMID- 7620617
TI  - BDNF produces analgesia in the formalin test and modifies neuropeptide levels in
      rat brain and spinal cord areas associated with nociception.
AB  - Previous studies have demonstrated an antinociceptive effect of brain-derived
      neurotrophic factor (BDNF) following infusion into the midbrain, near the
      periaqueductal grey and dorsal raphe nuclei. BDNF administration attenuated the
      behavioural response in the tail-flick and hot-plate tests, two models employing
      a phasic, thermal high-intensity nociceptive stimulus; the present studies extend
      our previous findings to include a model of moderate, continuous pain resulting
      from a chemical stimulus, the formalin test. Midbrain infusion of BDNF decreased
      the behavioural paw flinch response to subcutaneous formalin injection in both
      the early and late phases of the test. As our previous studies showed that BDNF
      induced analgesia was reversible by naloxone, we have examined the effects of
      BDNF administration on brain and spinal cord levels of neuropeptides involved in
      the modulation of nociceptive information, including the endogenous opioid
      peptides, met-enkephalin and beta-endorphin, as well as substance P and
      neuropeptide Y (NPY). At the site of infusion, within the PAG and dorsal raphe,
      BDNF increased the level of beta-endorphin by 63%, but had no effect on substance
      P, metenkephalin or NPY levels. In the dorsal spinal cord, substance P (113%
      increase), beta-endorphin (97% increase) and NPY (64% increase) were elevated,
      although ventral spinal cord levels of these peptides remained unchanged. These
      studies demonstrate a modulatory effect of BDNF on relevant neuropeptides within
      areas of the brain and spinal cord involved in the processing of nociceptive
      information.

PMID- 7620615
TI  - alpha-Bungarotoxin-sensitive nicotinic receptors on bovine chromaffin cells:
      molecular cloning, functional expression and alternative splicing of the alpha 7
      subunit.
AB  - Chromaffin cells from the bovine adrenal medulla express alpha-bungarotoxin
      sensitive acetylcholine receptors whose subunit composition is unknown. Northern
      blot analysis showed that the alpha 7 subunit, a main component of these alpha
      bungarotoxin-sensitive acetylcholine receptors in avian and rat brain, is
      expressed in chromaffin cells. The cDNA of this bovine alpha 7 subunit was cloned
      by polymerase chain reaction amplification of adrenal medulla RNA for detailed
      characterization of structure and function. The protein-coding region revealed
      92% amino acid sequence identity to rat alpha 7 and 89% to chicken alpha 7
      subunits. The alpha-bungarotoxin affinity of alpha 7 homomers expressed in
      Xenopus oocytes was similar to that observed previously with native chromaffin
      alpha-bungarotoxin-sensitive acetylcholine receptors. Cross-linking and sucrose
      gradient experiments suggested that, like the muscular and neuronal acetylcholine
      receptors; the alpha 7 receptor has a pentameric structure. Upon activation with
      nicotinic agonists the alpha 7 receptor exhibited rapidly desensitizing cation
      currents that were blocked by nicotinic antagonists and showed inward
      rectification. The amplification of adrenal medulla RNA by reverse transcription
      polymerase chain reaction methods revealed an alternatively spliced isoform of
      the bovine alpha 7 subunit, where the exon that codes for the M2 transmembrane
      segment was skipped during mRNA processing. Oocyte expression of this isoform
      does not yield functional channels. However, this alternative mRNA exhibits dose
      dependent inhibition of alpha 7 homomer expression when coinjected with the
      undeleted isoform.

PMID- 7620618
TI  - The influence of premotor interneuron populations on the frequency of the spinal
      pattern generator for swimming in Xenopus embryos: a simulation study.
AB  - Our aim was to test the hypothesis that the frequency of neuronal rhythm
      generating networks is partly controlled by the size of the active premotor
      interneuron population. We have tested possible mechanisms for frequency changes
      in a population model of the Xenopus laevis embryo spinal rhythm-generating
      networks for swimming. After initiation by a brief sensory excitation, the
      frequency of swimming activity decreases to a steady level determined by the
      properties of the 24 interneurons and their connections. The initial frequency
      decrease was dependent on the time-course of initiating sensory synaptic
      excitation. When some premotor excitatory interneurons were given weaker synaptic
      connections to reflect the variability in the spinal cord, they could drop out
      and stop firing during the initial frequency decrease while swimming activity
      continued. If the synaptic input of such weak excitatory interneurons was graded
      finely, they could drop out consecutively. This led to further decreases in the
      level of tonic excitation and in network frequency which depended on the number,
      type and distribution of excitatory interneurons that stopped firing. Silent weak
      excitatory interneurons could be recruited by a second sensory excitation and
      cause an increase in tonic depolarization and frequency which outlasted the
      sensory input. Such recruitment could occur on both sides after local sensory
      stimulation to only one region or one side of the model. We conclude that these
      computer simulations support the hypothesis that premotor interneuron drop-out
      and recruitment is one mechanism which can control frequency in a locomotor
      central pattern generator.

PMID- 7620619
TI  - Double in situ hybridization reveals overlapping neuronal populations expressing
      the low molecular weight GTPases Rab3a and Rab3b in Rat brain.
AB  - The ras-related Rab3 gene subfamily codes for small GTP-binding proteins which
      control a late step of exocytosis during which vesicles become docked to the
      plasma membrane. Rab3a and Rab3b are the most abundant Rab3 isoforms expressed in
      the CNS of mammals. We have shown previously that the Rab3a protein was
      selectively distributed and expressed in various regions of the rat brain. Here
      we have determined the pattern of expression of Rab3b mRNA in the brain and
      compared it with that of Rab3a mRNA. In addition, we examined the co-expression
      of these two Rab within individual neurons. In general the Rab3b transcript was
      detected in many regions which also express Rab3a mRNA but at a lower level than
      Rab3a, except in the olfactory bulb and in the pituitary where the Rab3b
      hybridization signal was similar and higher respectively. Double in situ
      hybridization revealed that Rab3a and Rab3b mRNAs were co-localized in most
      neurons, in all brain areas examined. However, in each of these areas, subsets of
      neurons appeared to preferentially express either Rab3b or Rab3a, or some neurons
      did not express either Rab3 homologue at detectable levels. These data support
      the view of a functional specialization of Rab3a and Rab3b in the control of
      exocytosis in neuronal and neuroendocrine cells.

PMID- 7620620
TI  - Ontogeny of the D1 dopamine receptor in the rat striatonigral system: an
      immunohistochemical study.
AB  - Antibodies were raised against a recombinant protein to analyse the pre- and
      postnatal ontogeny of the neurons expressing the D1 dopamine receptor in the
      striatum by immunohistochemistry. We report that D1 immunoreactivity is
      detectable from gestational day (G) 15 and is distributed homogeneously
      throughout the striatum from G15 to G18. From G19-20 to postnatal day (P) 3, D1
      immunoreactivity becomes heterogeneous and predominates in cell bodies of the
      patch compartment while very limited immunoreactivity is detectable in the
      matricial compartment. The differential intensity between patches and matrix
      reaches its peak around P0. From P2, the pattern of D1 immunoreactivity
      progressively assumes the homogeneous distribution characteristic of the adult
      striatum. The expression of D1 mRNA in striatal neurons, as investigated by in
      situ hybridization, displays a similar pattern during this period. Substance P
      mRNA is also preferentially expressed in the patch compartment during the same
      period. D1 immunoreactivity appears at G17 in the substantia nigra as clusters of
      fibres and increases subsequently until reaching its adult form during the first
      postnatal week. These results demonstrate that the two compartments of the
      developing striatum display differential transcriptional and translational
      activity for the D1 gene and consequently two different and successive patterns
      of expression of D1 protein: patch neurons first express D1 receptor intensely
      while matrix neurons express it later and in smaller amounts so that D1 receptor
      appears transiently during the perinatal period as a marker of the patch
      compartment.

PMID- 7620621
TI  - Axonal target choice and dendritic development of ferret beta retinal ganglion
      cells.
AB  - We have investigated the relationship between axon targeting and dendritic
      morphology in beta retinal ganglion cells in the postnatal ferret. Axonal
      projections were assessed by making separate injections of different fluorescent
      retrograde tracers into either the superior colliculus or lateral geniculate
      nucleus in vivo. The dendritic morphology of retrogradely labelled cells was
      revealed by the in vitro intracellular injection of lucifer yellow in fixed
      retina. In this way, 405 retinal ganglion cells were triple- or double-labelled
      and characterized by their dendritic branching styles. Both the distinct
      dendritic morphology of beta cells and the characteristic restriction of their
      adult axonal terminals to the lateral geniculate nucleus emerge postnatally. Beta
      cell dendritic morphology is established between postnatal days 5 and 9. As in
      the cat (Ramoa et al., 1989), beta cells extend and then retract a projection to
      the superior colliculus as part of their normal development. Transient beta
      axonal collaterals to the superior colliculus persist beyond the period of cell
      death, but nearly all are withdrawn by postnatal day 15. No dendritically
      distinct beta cell projects to the superior colliculus alone, at any age.
      Heterochronic injections of different colours of retrograde tracer into the
      superior colliculus were used to study changes in the complement of the
      retinocollicular projection over time. A significant proportion of cells (58%)
      labelled at postnatal day 0 from the superior colliculus, which subsequently
      survived the period of cell death, were found to be beta cells that could no
      longer be demonstrated to have a retinocollicular axon.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7620623
TI  - alpha-latrotoxin is a potent inducer of neurotransmitter release in Torpedo
      electric organ--functional and morphological characterization.
AB  - In this report we show that alpha-latrotoxin from black widow spider venom is a
      potent activator of neurotransmitter release in synaptosomes from the Torpedo
      electric organ. Binding of the purified toxin (5 nM) to the synaptosomal fraction
      occurs already at 4 degrees C and is dependent on the presence of divalent ions.
      However, neurotransmitter release commences only after temperature elevation (22
      degrees C) and is completed within 2 min. The effect of alpha-latrotoxin on
      release is achieved at 1 nM and is already saturated at 5 nM. The release is
      stimulated by the presence of Ca2+ ions. Activation of release by alpha
      latrotoxin is accompanied by morphological changes in electric organ
      synaptosomes. The synaptosomes swell, resulting in a 55% increase in section
      area. Moreover, the number of synaptic vesicles per unit area decreases about
      three-fold, and rows of docked synaptic vesicles are rarely detected as opposed
      to control synaptosomes. These morphological changes indicate that the massive
      release is mainly due to synaptic vesicle fusion. alpha-Latrotoxin binding sites
      are highly concentrated in the innervated face of the electrocytes.
      Immunoelectron microscopy on electric organ sections reveals alpha-latrotoxin
      binding sites over the entire plasma membrane at release sites and facing Schwann
      cells surrounding Torpedo nerve terminals. Surprisingly, a high concentration of
      binding sites is also found at structures surrounding branching unmyelinated
      axons. This staining is in close proximity to Schwann cell envelopes and to the
      basal lamina around axonal tips. The mode of action of alpha-latrotoxin in view
      of the localization of its binding sites is discussed.

PMID- 7620622
TI  - Development and pharmacological suppression of secondary afterdischarges in the
      hippocampus of amygdala-kindled rats.
AB  - The development and spread of afterdischarges in the ipsilateral limbic system
      during amygdala kindling, a model of complex partial seizures, was studied in
      male and female rats. Kindling stimulation was performed in the basolateral
      amygdala, and afterdischarges were recorded from the stimulation electrode and
      electrodes in the nucleus accumbens, the posterior piriform cortex and the
      ventral hippocampus, all implanted on the right side of the brain. All structures
      showed primary afterdischarges already after the first stimulation, indicating a
      close anatomical and physiological connection to the epileptogenic focus. The
      development of robust secondary afterdischarges, which occurred after the end of
      the primary afterdischarges in the amygdala and which always originated in the
      hippocampus but also spread to one or more of the other recording sites, is
      described. The secondary afterdischarges initially occurred after about nine
      kindling stimulations in both male and female rats, and were associated with an
      increase in primary afterdischarge duration and a progression from focal to motor
      seizures. In order to test the effect of common antiepileptic drugs on the
      secondary afterdischarges, a group of female rats were treated with valproate,
      carbamazepine or phenytoin. All drugs suppressed the secondary afterdischarges,
      although they had a different anticonvulsant efficacy on motor seizures and
      afterdischarge duration after amygdala stimulation. While valproate and
      carbamazepine dose-dependently reduced all parameters of the kindled seizure,
      including the secondary afterdischarges in the hippocampus, phenytoin suppressed
      the secondary afterdischarges also in the absence of any anticonvulsant effect,
      suggesting that recurrent hippocampal activation is not crucial for the kindled
      state.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7620624
TI  - Neuronal signalling of information important to visual recognition memory in rat
      rhinal and neighbouring cortices.
AB  - This study was conducted to discover whether the rat cortex contains neurons that
      signal information concerning the previous occurrence of stimuli, as has been
      found in the primate. Recordings of the activity of 396 single neurons were made
      while unanaesthetized rats were shown objects. The effects on neuronal
      responsiveness of stimulus repetition and of the relative familiarity of the
      stimuli were sought. The areas sampled were the rhinal (entorhinal and
      perirhinal) cortex, area TE of the temporal cortex, the lateral occipital cortex
      and the hippocampal formation. The response to the first presentations of objects
      was significantly different from that to their second presentations for 63 (34%)
      of the 185 responsive neurons; for 39 of the neurons the response was smaller
      when the stimulus was repeated, whereas for 24 it was larger. The incidence of
      decremental responses was higher in the non-hippocampal cortex than in the
      hippocampal formation, while the incidence of incremental responses was higher in
      the hippocampal formation than other cortical areas. The response to unfamiliar
      objects was significantly different from that to highly familiar objects for 15
      (22%) of 67 responsive neurons so tested; for 12 of the neurons the response was
      smaller when the stimulus was repeated, and for three it was larger; most of
      these neurons were found in area TE. The responses of ten familiarity neurons
      varied significantly with the relative familiarity of the stimuli but not with
      stimulus repetition; the responses of seven recency neurons varied significantly
      upon stimulus repetition but not with the relative familiarity of the stimuli.
      Thus information concerning stimulus repetition and familiarity is separably
      encoded at the single neuron level in the rat cortex. The results demonstrate
      that in the rat cortex as in the monkey cortex there are neurons that signal
      information concerning the prior occurrence of stimuli; such information is of
      importance to recognition memory, working memory and priming memory.

PMID- 7620625
TI  - Neurophysiological investigations of a recognition memory system for imprinting
      in the domestic chick.
AB  - The responsiveness of neurons in a region of the chick brain involved in the
      learning process of imprinting, the right intermediate and medial hyperstriatum
      ventrale (right IMHV), has been investigated in unanaesthetized, trained and
      untrained chicks. The results demonstrate that neuronal responsiveness in this
      region reflects a variety of behavioural consequences of imprinting and is
      markedly altered as a result of the learning process. Groups of chicks (nine in
      each group) were either dark-reared or trained (imprinted) by exposure to a
      rotating red box or a rotating blue cylinder. Recordings of single or small
      groups of neurons were subsequently made from 156 sites in the right IMHV while
      the 2-day-old chicks were free to move in a running wheel. There was a highly
      significant increase in the proportion of sites responsive to the stimulus used
      to train the birds compared to the proportion responsive to that stimulus in dark
      reared birds (30 and 9% respectively). These changes were found when either the
      red box or the blue cylinder was used to train the bird, the changes being
      similar for both stimuli. There was also a significant increase in the mean
      magnitude of the change in neuronal activity on stimulus presentation for the
      training stimulus compared to the same stimulus when not used in the bird's
      training. No significant effects of the training experience of the chicks were
      found upon either the magnitude of evoked activity or the proportion of sites
      responsive to a rotating stuffed jungle fowl or the sound of the maternal call.
      The presence of the training stimulus was selectively signalled by the response
      at certain sites. At other sites there was response generalization across
      stimulus shape or colour. A comparison with results for the left IMHV
      demonstrates both similarities and differences in neuronal responsiveness between
      the two regions. In both regions imprinting selectively enhances neuronal
      responsiveness to the training stimulus. However, for trained birds the mean
      proportion of sites responding to whichever of the red box or the blue cylinder
      was not used in the bird's training was significantly lower in the right than the
      left IMHV. These results are discussed in relationship to previously reported
      asymmetries in the response of the right and left IMHV regions to imprinting. A
      model is introduced to explain the physiological findings. The effects of
      training on right IMHV neuronal function are consistent with a long-term role for
      this region in the recognition memory of imprinting.

PMID- 7620626
TI  - Expression of the homeobox-containing gene En-2 during the development of the
      chick central nervous system.
AB  - The expression of the homeobox-containing gene En-2 was analysed with the
      monoclonal antibody 4D9 in the chick central nervous system throughout
      embryogenesis. Confirming previous studies, early expression of the En-2 protein
      [beginning at stage 9 of Hamburger and Hamilton (HH9)] is restricted to a portion
      of the neural tube containing the primordia of the cerebellum, the isthmic region
      and the mesencephalic grisea, and forms a double gradient decreasing both
      caudally and rostrally from a high point located around the midbrain-hindbrain
      constriction. This mes-isthmo-cerebellar region contains all the En-2-positive
      germinative cells and the great majority of the En-2-positive postmitotic neurons
      throughout embryogenesis. Nevertheless, as the postmitotic neurons appear, En-2
      expression also occurs outside this region: in two columns of non-motoneuron
      cells in rhombomeres two to four (between HH20 and HH30) and, from HH24 onwards,
      throughout the grey matter of the lumbar and thoracic spinal cord, with the
      exception of the ventral motoneuron columns. Here, a detailed description of En-2
      expression is provided for the mes-isthmo-cerebellar region at stages HH30-32
      [embryonic day (E) 7], HH37 (E11) and HH46 (E21, hatching). This allows the
      visualization of cellular groups with heterogeneous patterns of En-2 expression,
      which are specific for each group in the intensity of En-2 expression, the
      distribution of the labelled cells and the temporal regulation of the gene. The
      use of tyrosine hydroxylase antiserum shows coexpression of the tyrosine
      hydroxylase enzyme and En-2 protein in the caudal part of the nuclei tegmenti
      pedunculo-pontinus, the area ventralis of Tsai and the substantia grisea
      centralis, but not in the locus coeruleus. In the cerebellum, the first
      expression, which is located in the deep nuclei and parasagittal bands of
      Purkinje cells, is down-regulated when the molecular layer interneurons and the
      granular cells begin to express the gene, at the end of embryogenesis. Finally,
      at hatching, En-2 expression permits the visualization in the cerebellum of a
      population of small En-2-negative cells located around the Purkinje cells that
      may correspond to those described in chick/quail chimaeras as having an origin
      different from that of the bulk of granular neurons.

PMID- 7620627
TI  - Functional involvement of sciatic nerve-derived versican- and decorin-like
      molecules and other chondroitin sulphate proteoglycans in ECM-mediated cell
      adhesion and neurite outgrowth.
AB  - We have previously described two proteoglycans from human sciatic nerve which are
      immunochemically related to the chondroitin sulphate proteoglycans versican and
      decorin. The chondroitin sulphate of the versican-like molecule and the core
      protein of the decorin-like molecule have been found previously to be up
      regulated after lesioning the adult mouse sciatic nerve. To investigate if the
      versican- and decorin-like molecules are involved in cell-extracellular matrix
      interactions, we studied the effect of both molecules on cell adhesion. The
      versican- and decorin-like molecules, substrate-coated in a mixture with
      fibronectin, but not with laminin or collagen types I or IV, inhibited the
      adhesion of several cell lines, neonatal dorsal root ganglion neurons and Schwann
      cells. The inhibitory activity was concentration-dependent and mediated by the
      chondroitin sulphate. Furthermore, when different proteoglycans were incubated
      with fibronectin, only the versican- and decorin-like molecules and the
      chondroitin sulphate proteoglycan aggrecan, but not the heparan sulphate
      proteoglycan perlecan, were able to inhibit fibronectin-mediated cell adhesion.
      The versican- and decorin-like molecules, substrate-coated alone or in a mixture
      with fibronectin or laminin, were at most slightly inhibitory to neurite
      outgrowth from PC12 phaeochromocytoma cells and neonatal dorsal root ganglion
      neurons. In a solid-phase ligand-binding assay the versican- and decorin-like
      molecules interacted with fibronectin, but not with laminin or collagen types I
      and IV. Binding of the versican-like molecule to fibronectin and inhibition of
      cell adhesion by this molecule was mediated via the heparin and cell-binding
      domains of fibronectin. These observations suggest that binding of the two
      proteoglycans to fibronectin is involved in the modulation of adhesion of cells
      to fibronectin.

PMID- 7620628
TI  - Electrophysiological characterization of a novel conotoxin that blocks molluscan
      sodium channels.
AB  - A novel peptide toxin, PnIVB, isolated from the venom of Conus pennaceus blocks
      voltage-gated sodium current in Aplysia neurons. Complete blockade is obtained at
      a PnIVB concentration of 80 +/- 2.2 nM and 50% blockade at 16 +/- 0.86 nM. The
      potency of PnIVB in blocking Aplysia sodium current is four orders of magnitude
      larger than that of tetrodotoxin. The toxin has no paralytic activity when
      injected into fish. The rapid blockade of sodium current by PnIVB is not
      associated with a change in the activation or inactivation kinetics of the
      current, or with the reversal potential. Sodium current blockade is reversible
      after a 30 min wash with 50 times the bath volume. The novel conotoxin PnIVB can
      be used as a powerful tool for mollusc neurobiological research and as a
      molecular probe to explore the structure-function relations of voltage-gated
      sodium channel subtypes.

PMID- 7620630
TI  - Laufband therapy based on 'rules of spinal locomotion' is effective in spinal
      cord injured persons.
AB  - Rehabilitation of locomotion in spinal cord (s.c.) injured patients is
      unsatisfactory. Here we report the effects of a novel 'Laufband (LB; treadmill)
      therapy' based on 'rules of spinal locomotion' derived from lower vertebrates.
      Eighty-nine incompletely paralysed (44 chronic and 45 acute) para- and
      tetraplegics underwent this therapy, then were compared with 64 patients (24
      chronic and 40 acute) treated conventionally. The programme consisted of daily
      upright walking on a motor driven LB initially with body weight support (BWS)
      provided by a harness and assisted limb movements by the therapists when
      necessary. Forty-four chronic patients with different degrees of paralysis
      undertook the programme for 3-20 weeks (median = 10.5), 0.5-18 years after s.c.
      damage. At the onset of LB therapy 33/44 patients were wheelchair-bound (no
      standing and/or walking without help by others) whereas at the end of therapy 25
      patients (76%) had learned to walk independently, 7 patients with help
      [corrected]. Only 1 subject did not improve. It was striking that voluntary
      muscle activity in the resting position was still low in several patients who had
      gained walking capability. Eleven patients who could already walk before LB
      therapy improved in speed and endurance. Of the 44 patients, six were capable of
      staircase walking before LB therapy compared with 34 afterwards. In order to
      validate the apparent superiority of LB therapy two types of comparisons were
      performed. In a 'temporal' control 12 spastic paretic patients, still wheelchair
      bound after the period of postacute conventional therapy, performed LB
      immediately thereafter. After completion of LB therapy nine of these patients had
      learned to walk without help from others.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7620629
TI  - Antibodies to postsynaptic PKC substrate neurogranin prevent long-term
      potentiation in hippocampal CA1 neurons.
AB  - Both pre- and postsynaptic protein kinase C have been implicated in long-term
      potentiation. Neurogranin (also known as BICKs and RC3) is a neuronal
      postsynaptic protein kinase C substrate. In the present study we injected
      monoclonal IgGs that recognize the protein kinase C phosphorylation site in
      neurogranin and B-50 (GAP-43), and that have been shown to inhibit protein kinase
      C-mediated B-50 phosphorylation, through a whole-cell clamp pipette into CA1
      pyramidal neurons in rat hippocampal slices. Injection of neurogranin IgGs, but
      not of control IgGs, prevented the induction of tetanus-induced long-term
      potentiation without affecting post-tetanic potentiation. Our results suggest
      that neurogranin is involved in mechanisms of activity-dependent synaptic
      plasticity.

PMID- 7620631
TI  - Elision: a method for accommodating multiple molecular sequence alignments with
      alignment-ambiguous sites.
AB  - The process of multiple sequence alignment provides homology statements for the
      phylogenetic analysis of molecular data. Unfortunately, multiple alignments are
      frequently nonunique. Two sources of these multiple alignments are analysis based
      on different sets of alignment parameter values (gap:change cost ratios) and
      nonunique equally costly alignments based on a single set of alignment
      parameters. By "eliding" these individual alignments into a single grand
      alignment, phylogeny that is weighted toward those positions that align more
      consistently can be reconstructed. Positions that show greater variation among
      alignments will be relatively downweighted. The technique results in a weighting
      procedure that is a posteriori and based on the evidence established from the
      original sequence alignments.

PMID- 7620632
TI  - Systematics of cetaceans using restriction site mapping of mitochondrial DNA.
AB  - Phylogenetic analysis of 14 cetacean species, including members from two baleen
      whale families and three toothed whale families, was undertaken using restriction
      site mapping of mitochondrial DNA and using cladistic and distance measures to
      infer phylogenies. The amount of between-taxa sequence divergence inferred from
      the data was lower than expected from the standard interpretation of the fossil
      record, but more consistent with some recent estimates of sequence divergence in
      cetacean mitochondrial DNA or nuclear DNA. This implies either that the rate of
      molecular evolution of cetacean DNA is much lower than that of other mammalian
      orders or that the fossil record of cetaceans requires reinterpretation. The
      incompleteness of the cetacean fossil record precludes resolution of the paradox
      at the present time. However, this discrepancy could in part be attributed to the
      sampling error inherent in the restriction site mapping technique, as comparative
      studies using the complete mtDNA genome and restriction site data of the blue and
      fin whales (genus Balaenoptera) indicate that the restriction site maps
      underestimate sequence divergence by about 40%. In contrast to a recent study
      suggesting that toothed whales were paraphyletic, with the sperm whales being
      more closely related to the rorquals than to the other toothed whales, the
      restriction data tend to support the monophyly of the baleen and the toothed
      whales, a finding which is consistent with a recent molecular-based study and
      with morphological and paleontological data. Topologies of the subfamily and
      generic levels are generally consistent with morphologically based schemes.

PMID- 7620633
TI  - Mitochondrial-DNA sequence evidence on the phylogeny of Australian jack-jumper
      ants of the Myrmecia pilosula complex.
AB  - Australian ants of the Myrmecia pilosula species complex include some individuals
      (in M. croslandi) with the lowest possible metazoan chromosome number of 2n = 2.
      Others in this cluster of sibling species have much higher numbers, the known
      maximum being 2n = 32. Two species (M. pilosula and M. 'banksi') are believed on
      cytogenetic and morphological grounds to have hybridized over a long period. To
      investigate the phylogeny and age of this group relative to the congeneric
      outgroup species M. gulosa, we sequenced part of the cytochrome b gene and the
      intergenic sequence between it and a primer anchored on the nearby tRNA(UCNSer)
      gene and analyzed the coding region using bootstrapped parsimony and neighbor
      joining trees using the numbers of synonymous and nonsynonymous codons per site.
      The intergenic space demonstrated a profusion of repeated sequences, and only
      very closely related sequences (as judged by that for cytochrome b) showed
      detectable similarity at this almost 100% A+T region. In agreement with
      predictions from karyotype studies, the phylogenetic analyses showed that M.
      croslandi is the sister group to the other siblings; the time of separation of M.
      croslandi from the rest of the pilosula group is unexpectedly ancient. Other
      relationships were poorly resolved, but the results suggest that M. 'banski' and
      M. pilosula cluster together, as expected on cytogenetic grounds, and the
      tentative suggestion of close affinity of the M. pilosula samples and two "PB"
      samples supports derivation of PB from female M. pilosula and male M. 'banksi.'

PMID- 7620636
TI  - A frequency-dependent significance test for parsimony.
AB  - We describe techniques for assessing evolutionary trees constructed by the
      parsimony criteria, when sequences exhibit irregular base compositions. In
      particular, we extend a recently described frequency-dependent significance test
      to handle any number of taxa and describe a modification of the Kishino-Hasegawa
      sites test. These modifications are useful for detecting historical signals
      beyond those patterns which arise purely from irregular base compositions between
      the compared sequences. We apply the test to extend our earlier studies on
      chloroplast origins using 16S rDNA sequences, where a failure to compensate for
      irregular base compositions between the compared sequences provides statistically
      significant support for unjustified phylogenetic inferences. We also describe how
      the techniques can be modified to determine how "tree-like" data are, given
      independent variation in the base frequencies.

PMID- 7620635
TI  - Estimation of confidence in phylogeny: the complete-and-partial bootstrap
      technique.
AB  - The bootstrap is a statistical technique that is widely used to assess confidence
      limits on phylogenies. We show that the power of the bootstrap test is lower than
      those of the C and S tests suggested by Felsenstein, unless the critical value
      employed in the bootstrap test is correctly selected. If the 95% critical value
      is used, the bootstrap proportions are underestimates of the confidence level
      when the number of possible alternative topologies is three or more; the degree
      of underestimation increases with the number of competing alternative topologies.
      To overcome this problem, we propose the complete-and-partial bootstrap technique
      as a method for obtaining an unbiased estimate of the confidence level. The
      method is based on a multinomial model of many alternatives among which the
      choice is to be made. The complete-and-partial bootstrap technique can be used to
      estimate the effective number of competing alternative topologies and the
      confidence level of the monophyly of a particular group of taxa or of an inferred
      tree topology. This approach can be used with the maximum parsimony or neighbor
      joining tree reconstruction method.

PMID- 7620634
TI  - Opsin phylogeny and evolution: a model for blue shifts in wavelength regulation.
AB  - The vast diversity in spectral sensitivities in the vision of many organisms is
      mediated mostly (although not entirely) through variation in the photosensitive
      visual pigments (opsins) of the eye. Specifically, shifts in absorption maxima of
      visual pigments are thought to be a result of interactions within the binding
      pocket of the opsin, between amino acid side chains and the retinal chromophore,
      However, it has proven difficult to identify specific amino acid residues
      important in determining wavelength absorption maxima, especially for some of the
      short wavelength (blue) opsins. In this paper, a comparative phylogenetic
      approach was applied to opsin protein sequence data to identify residues
      important in opsin wavelength regulation. In essence, this approach consisted of
      interpreting evolutionary history as a series of experiments in which natural
      selection has repeatedly favored amino acid replacements of certain residues to
      shift the opsin absorption spectra to either shorter or longer wavelengths. Opsin
      protein sequences were obtained from GenBank, aligned, and used to reconstruct a
      phylogenetic tree. Amino acid replacements were traced along the branches of this
      opsin tree, focusing only on residues likely to reside within the chromophore
      binding pocket. A number of functionally convergent, nonconservative amino acid
      replacements in independently evolved opsins with similar shifts in spectral
      properties were identified. In short, reconstruction of the phylogeny of the
      opsin molecule allowed us to track amino acid substitutions in specific sites
      within the opsin and to target those particular substitutions that are repeatedly
      associated with marked changes in peak absorbance, shifting the spectral
      sensitivity of the opsin toward shorter or longer wavelengths. Based on these
      results, we propose a model for blue shifts of opsin absorption spectra. Amino
      acid replacements of four polar and charged residues near the protonated Schiff
      base (SBH+) end of the chromophore are proposed to result in blue shifts of the
      opsin absorption spectra. This model may explain some of the diversity of blue
      opsins apparent in both vertebrates and invertebrates.

PMID- 7620637
TI  - The phylogenetic position of the pterobranch hemichordates based on 18S rDNA
      sequence data.
AB  - Pterobranchs are a class of deuterostome metazoans that are sessile marine
      suspension feeders. Although this group has been poorly studied, understanding
      their phylogenetic affinities is central to understanding early metazoan
      evolution. Sequence data from the 5' end of the 18S rDNA gene was collected from
      a pterobranch, Rhabdopleura normani, and combined with other available 18S
      sequences. Using standard phylogenetic methods, the evolutionary relationships of
      deuterostome metazoans were reconstructed. The pterobranchs are most closely
      related to the enteropneust hemichordates. This was confirmed by bootstrap
      analyses and a topology-dependent cladistic permutation tail probability (T-PTP)
      test. My analysis agrees with Turbeville et al.'s (1994) and Wada and Satoh's
      (1994) finding that hemichordates are more closely related to echinoderms than to
      chordates, and it is proposed that Metschnikoff's (1881) name Ambulacraria be
      adopted for the clade defined by the last common ancestor of the hemichordates
      and echinoderms. These findings suggest that ciliated gill slits and the dorsal
      hollow nerve chord are pleisomorphic features of the Deuterostomia.

PMID- 7620638
TI  - Phylogenetic relationships among karyorelictids and heterotrichs inferred from
      small subunit rRNA sequences: resolution at the base of the ciliate tree.
AB  - Ciliate protozoa are among the most diverse and complex cells that have been
      described. Ciliates are characterized by nuclear dimorphism, possessing a
      macronucleus and a micronucleus which share the same cytoplasm. An understanding
      of the evolution of ciliate diversity depends upon knowledge of their phylogeny.
      In this study we attempted to resolve some of the relationships at the base of
      the ciliate tree by determining the phylogenetic position of a sample of
      heterotrich and hypothesized primitive karyorelictid ciliates. Karyorelictids are
      considered primitive because they possess a "simple" form of nuclear dualism
      whereby the macronucleus does not divide once it has differentiated from a
      micronucleus. We micromanipulated cells of two heterotrichs, Spirostomum ambiguum
      and Gruberia sp., and two karyorelictids, Loxodes magnus and Tracheloraphis sp.,
      and amplified their small subunit (SSU) rDNA using PCR. The primary structure of
      the SSU rDNA was determined for each species and used to infer their positions in
      the ciliate phylogenetic tree. The results indicate, with strong support, that
      the aerobic heterotrichs and the karyorelictids sampled constitute a monophyletic
      group. The most parsimonious interpretation of the form of nuclear dimorphism in
      karyorelictids is that it is derived from the general condition as found in its
      sister group the aerobic heterotrichs. The two anaerobic heterotrichs, Metopus
      contortus and Metopus palaeformis, comprise a distinct clade, so that the
      subclass Heterotrichia, as currently conceived, is not a monophyletic group. The
      complex mouth architecture which characterizes all heterotrichs must be
      reassessed in light of this finding.

PMID- 7620639
TI  - Origin of West Indian populations of the geographically widespread boa Corallus
      enydris inferred from mitochondrial DNA sequences.
AB  - Corallus enydris (Serpentes: Boidae: Boinae) is an arboreal snake with an
      extremely wide mainland distribution from southern Costa Rica to southeastern
      Brazil and is one of two boine species that has invaded the Lesser Antilles
      (Grenada Bank and St. Vincent). Mitochondrial DNA sequences of samples from seven
      geographically disparate localities provided evidence of phylogenetic
      relationships. The monophyly of C. enydris is corroborated and a major dichotomy
      between northern samples (Panama and Trinidad) and southern samples (Guyana,
      Peru, southeastern Brazil) was found and corresponds to the two currently
      recognized subspecies. Unexpectedly, the two samples from the West Indies
      (southern Lesser Antilles) cluster with the southern rather than the
      geographically closer northern samples (e.g., Trinidad). The results imply a
      fairly recent Guianan-Amazonian origin of West Indian populations.

PMID- 7620640
TI  - Support for the hypothesis of anguimorph ancestry for the suborder Serpentes from
      phylogenetic analysis of mitochondrial DNA sequences.
AB  - Snakes represent one of the most ubiquitous and successful groups of terrestrial
      vertebrates; however, many aspects of their evolutionary relationships remain
      uncertain. Previous research, which utilized morphological and immunological
      data, has not resolved the origin of snakes or clearly delineated the
      relationships between snakes and other lizards. A DNA sequence data set from the
      mitochondrial ND4 gene and the histidine, serine, and leucine tRNAs has been
      generated for use in the examination of these relationships. Parsimony analyses
      employing multiple outgroups resolve snakes within the lizard clade. Varanus is
      the sister group to the snakes in 81% of bootstrap replications using Bos as the
      outgroup specified, 85% using Trachemys, 57% using Alligator, and 80% using all
      three outgroups. The primitive, fossorial snake genera Leptotyphlops and Typhlops
      are basal to the other snakes and provide tentative molecular evidence in support
      of a fossorial or subfossorial origin of limblessness for the suborder Serpentes.

PMID- 7620641
TI  - Kinetics of cycle length dependence of ventricular repolarization: effect of
      autonomic blockade.
AB  - INTRODUCTION: Beat-to-beat adaptation of ventricular repolarization duration to
      cardiac cycle length and autonomic activity has not been previously characterized
      in the spontaneously beating human heart. METHODS AND RESULTS: The ECG of 14
      healthy subjects was recorded from the supine and upright positions. Autonomic
      blockade was accomplished by atropine and propranolol. RR and RT intervals were
      measured by a computer algorithm, and the impulse response (h) from RR to RT
      computed. In the supine position the maximal adjustment of the RT interval
      occurred in the first beat following a change in cycle length (hpeak = 17.8 +/-
      1.6 msec/sec), but continued to be detectable for 3.8 seconds (2.9-4.7 sec).
      Propranolol attenuated the peak impulse response to 15.8 +/- 4.0 msec/sec (P =
      NS). In the standing position the peak impulse response was increased to 25.2 +/-
      5.0 msec/sec (P = 0.004 vs supine), and the impulse response duration (hdur)
      shortened to 1.4 seconds (1.3-1.6). This was reversed by beta blockade (hpeak =
      10.7 +/- 3.6 [P = 0.005 vs standing]; hdur = 5.5 sec [4.8-6.1]). Parasympathetic
      and combined autonomic blockade resulted in too little residual heart rate
      variability to estimate the impulse response accurately. The slope of the
      regression of delta RT and delta RR in the supine position was 0.0177 +/- 0.0016,
      which was closely correlated with the peak impulse response (r = 0.91).
      CONCLUSIONS: System identification techniques can assist in characterizing the
      cycle dependence of ventricular repolarization and may provide new insights into
      conditions associated with abnormal repolarization.

PMID- 7620642
TI  - Effect of isoproterenol on accessory pathways without overt retrograde
      conduction.
AB  - INTRODUCTION: Absence of overt retrograde accessory pathway conduction may be
      related to low resting sympathetic tone in patients with apparent unidirectional
      anterogradely conducting accessory pathways (UACAP). METHODS AND RESULTS: To test
      this hypothesis, we studied the effect of isoproterenol on accessory pathway
      function and tachycardia induction in 18 patients (12 men and 6 women, ages 34 +/
      16 years [mean +/- SD]) with UACAP. After baseline study in the drug-free state,
      electrphysiologic testing was repeated during infusion of isoproterenol (0.5 to
      1.5 micrograms/min, titrated to increase heart rate by 20%). Isoproterenol
      shortened the anterograde effective refractory period (398 +/- 117 vs 305 +/- 63
      msec; P < 0.01; basic drive cycle length 600 msec) of the accessory pathway.
      However, retrograde accessory pathway conduction and atrioventricular reentrant
      tachycardia were exposed in only 3 (17%) patients by isoproterenol infusion. All
      3 patients with retrograde accessory pathway revealed after isoproterenol had
      clinically documented tachycardia (supraventricular tachycardia in 2, atrial
      fibrillation in 1) during exercise, while none of the patients with persistent
      absence of retrograde accessory pathway conduction had this symptom. CONCLUSIONS:
      We conclude that absence of overt retrograde conduction over accessory pathways
      may be related to low resting sympathetic tone in some individuals. Restoration
      of retrograde conduction with isoproterenol is unusual and most likely to be
      observed in patients with clinically documented paroxysmal supraventricular
      tachycardia related to exercise.

PMID- 7620643
TI  - Activation time determination by high-resolution unipolar and bipolar
      extracellular electrograms in the canine heart.
AB  - INTRODUCTION: To identify the optimal criteria for activation time (AT)
      determination of bipolar electrograms from normal hearts, a high-resolution cross
      electrode array comprising 128 unipolar electrodes of 500-microns spacing was
      used to record extracellular potentials from the left ventricular epicardium of
      12 dog hearts. METHODS AND RESULTS: Recordings were made during broad wavefront
      propagation (B wave) and local elliptical wavefront propagation (E wave).
      Characteristics of 863 bipolar electrograms (1-mm spacing) were constructed from
      unipolar data standardized for differences in polarity, then classified
      morphologically. Features for bipolar AT determination were compared to the time
      of the negative peak of the first temporal derivative of a unipolar electrogram
      situated mid-way between the bipoles. During B wave, three distinct morphologies
      were observed: uniphasic (61%), biphasic (23%), and triphasic (16%). Peak voltage
      of uniphasic and triphasic signals was the best predictor of AT (error: 0.6 +/-
      0.6 msec and 0.6 +/- 0.8 msec, respectively). During E wave, parallel orientation
      of the bipoles with respect to the direction of impulse propagation wavefront
      resulted in uniphasic signals (> 99%), while for perpendicular orientation of the
      bipoles, electrogram morphology was variable. For parallel orientation of the
      bipoles, peak negative voltage was the best predictor of AT for both longitudinal
      and transverse propagation, while for perpendicular bipole orientation, peak
      negative voltage was a less reliable predictor for propagation along both fiber
      axes. Increasing interpolar distance resulted in a degradation in AT accuracy for
      B wave (from 0.6 +/- 0.6 msec at 1 mm to 1.1 +/- 1.2 msec at 7 mm) and for E wave
      (from 0.4 +/- 0.3 msec at 1 mm to 3.1 +/- 2.9 msec at 7 mm). CONCLUSIONS: (1) The
      accuracy of bipolar electrograms is sensitive to wavefront direction, bipole
      orientation, and interpolar distance; (2) peak negative voltage of uniphasic and
      triphasic signals is a reliable predictor of AT, but only for B wave; (3) a
      maximum interpolar distance of 2 mm and bipole orientation parallel to the
      direction of the impulse wavefront are minimally required for accurate
      determination of AT during impulse propagation initiated near the recording
      electrodes; and (4) for impulses initiated near the recording site in normal
      tissue, a biphasic or triphasic morphology almost certainly indicates that the
      bipolar electrode is oriented perpendicular to the wavefront direction,
      irrespective of fiber orientation.

PMID- 7620645
TI  - Entrainment techniques for mapping atrial and ventricular tachycardias.
AB  - Many atrial tachycardias, atrial flutter, and postmyocardial infarction
      ventricular tachycardias are due to reentry through large "macroreentrant"
      circuits. These circuits can be difficult to define by catheter mapping of the
      activation sequence. Entrainment techniques allow the relation of a mapping site
      to the reentrant circuit to be assessed on a site-by-site basis during catheter
      mapping. Regions of abnormal conduction that are in the reentrant circuit can be
      distinguished from bystander sites outside the circuit. A mapping site
      classification to guide catheter ablation is reviewed.

PMID- 7620646
TI  - Radiofrequency catheter ablation versus modification of the AV node for control
      of rapid ventricular response in atrial fibrillation.
AB  - Atrial fibrillation is a common arrhythmia, which is frequently difficult to
      control. Symptoms and ventricular dysfunction may be caused by a rapid
      ventricular response to atrial fibrillation. Radiofrequency catheter ablation
      techniques for ventricular rate control have been developed, including AV node
      modification and AV node ablation with pacemaker implantation. For both AV node
      modification and ablation, radiofrequency energy is applied via a 4-mm tipped
      electrode catheter. For AV node ablation radiofrequency energy is applied near
      the compact AV node or His bundle via the right atrium, or occasionally at the
      His bundle via the left ventricle. For AV node modification radiofrequency energy
      is applied in the low middle or posterior septal right atrium near the tricuspid
      valve annulus. Both techniques can effectively control ventricular response to
      atrial fibrillation and the associated symptoms, although AV node modification is
      effective in only about 70% of patients compared to AV node ablation, which is
      effective in nearly 100%. In patients responding to AV node modification, maximal
      and mean ventricular response to atrial fibrillation is reduced by 25% to 35%
      chronically. Inadvertent AV block may occur during attempted AV node
      modification. It seems appropriate to attempt AV node modification prior to AV
      node ablation in patients with refractory atrial fibrillation and rapid
      ventricular response, in order to avoid the need for permanent pacemaker
      implantation. Although unproven, studies suggest that the mechanism by which AV
      node modification achieves ventricular rate control may be slow-pathway ablation
      in the low posterior septal right atrium.

PMID- 7620644
TI  - The effect of flunarizine and ryanodine on acquired torsades de pointes
      arrhythmias in the intact canine heart.
AB  - INTRODUCTION: Ryanodine, a specific blocker of the Ca2+ release channel of the
      sarcoplasmic reticulum, and flunarizine, a [Ca2+]i overload blocker, possess
      antiarrhythmic effects against delayed afterdepolarizations (DADs) and DAD
      dependent arrhythmias. In vitro controversy exists about their effect on early
      after-depolarizations (EADs): no effect was reported on cesium-induced EADs,
      while ryanodine did prevent EADs induced by isoproterenol. To study the possible
      role of intracellular Ca2+ overload in acquired EAD-dependent torsades de pointes
      (TdP) arrhythmias, we tested the effects of flunarizine and ryanodine in our
      animal model of TdP. METHODS AND RESULTS: Anaesthetized dogs with chronic AV
      block received d-sotalol or almokalant followed by pacing. A subset of dogs with
      reproducible TdP (> or = 3 times) were selected to receive flunarizine (2 mg/kg
      per 2 min) or ryanodine (10 micrograms/kg per 10 min). After d-sotalol, TdP was
      induced at a mean cycle length of the idioventricular rhythm (CL-IVR) of 2070 +/-
      635 msec and a QT(U) interval of 535 +/- 65 msec. Induction of TdP was prevented
      by flunarizine in all experiments (8/8): electrophysiologically this was
      associated with a decrease in CL-IVR, QT(U), and QTc interval (390 +/- 100 to 320
      +/- 45, P < 0.05). Ryanodine prevented TdP induction in 4 of 5 experiments and
      decreased the CL-IVR, QT(U), and the QTc interval from 385 +/- 75 to 320 +/- 20
      msec (P < 0.05). Both drugs also suppressed the almokalant-induced EADs and
      related ectopic activity. This antiarrhythmic action corresponded with the
      inability to reinduce TdP by pacing. CONCLUSIONS: Blockade of the Ca2+ release
      channel of the sarcoplasmic reticulum by ryanodine or the reduction of [Ca2+]i
      overload by flunarizine prevents induction of EAD-dependent acquired TdP
      arrhythmias, suggesting a role for [Ca2+]i overload in acquired TdP.

PMID- 7620647
TI  - Insights into the electrophysiology of atrial arrhythmias gained by the catheter
      ablation experience: "learning while burning, Part II".
AB  - Although the development and wide-scale application of catheter ablative
      techniques has drastically changed the practice of electrophysiology, catheter
      ablation does not preclude physiologic investigation. On the contrary, given the
      precise and directed nature of this technique and the increased attention to
      detailed cardiac mapping that it requires, catheter ablation may be viewed as a
      tool to provide unique information about arrhythmia substrates. In this article,
      the insights provided by the catheter ablation experience into the
      pathophysiology of the focal atrial arrhythmias, atrial tachycardia, sinus node
      reentrant tachycardia, and inappropriate sinus tachycardia will be reviewed.
      Atrial arrhythmias were initially difficult to treat with ablative therapy,
      particularly because they can occur anywhere within the atria and the experience
      with mapping for surgical ablation was quite limited. A number of novel
      approaches to atrial mapping have been developed in response to this challenge,
      and presently, catheter ablation provides effective therapy for the majority of
      patients with focal atrial arrhythmias. In addition, deliberate attempts at
      "learning while burning" have already begun to enhance our understanding of the
      interaction of the structural and electrophysiologic aspects of the substrate for
      atrial arrhythmias.

PMID- 7620648
TI  - The development of health policy in the EU.

PMID- 7620649
TI  - Volume measurement in lymphoedema treatment: examination of formulae.
AB  - The purpose of this study was to examine a variety of mathematical volume
      formulae and their respective validity in establishing limb volume in monitoring
      and evaluation of treatment for lymphoedema. Using a random sample of treatment
      records from the Day Ward, Worthing Hospital, it is shown that the formula most
      commonly used at present, that for a cylinder, produces imprecise volume data. A
      simplified formula derived from the formula for a frustum is tested, and is found
      to produce more accurate data. The paper proposes that the frustum formula is
      more appropriate in establishing limb volume, and should be adopted by
      practitioners.

PMID- 7620650
TI  - Bereavement referrals to a psychiatric service: an audit.
AB  - The majority of people who are bereaved will work through their grief with
      support from family and friends. Over 30%, however, may require professional
      support, and studies have shown that most people contact their General
      Practitioner and primary health-care team for counselling/support. Effective
      support and counselling can also be given by voluntary agencies. It was decided
      to audit the referrals made to a bereavement service for bereavement counselling
      to ascertain the level of support given prior to the referral and whether
      information had been given to the bereaved regarding the services available to
      them in the voluntary sector. Twelve referrals were received in the allotted time
      period, 10 of which were made within the first year of bereavement. Only one
      referral had been offered counselling by the primary health-care team and one
      other had been informed of voluntary bereavement support/counselling agencies.
      Two referrals had abnormal grief reactions requiring psychiatric intervention.
      Conclusions include raising the awareness of general practitioners and primary
      health-care teams of the normal grieving process, and increasing the provision of
      support for the bereaved. It is also suggested that the bereaved are made more
      aware of the services that voluntary agencies can provide.

PMID- 7620651
TI  - Fatigue in cancer patients: a review of the literature.
AB  - This paper reviews the research literature concerning fatigue in cancer patients,
      evaluating the quality of the evidence, thus helping to focus the direction and
      methodological rigour required in future investigations. Since fatigue in this
      population has been attributed to several mechanisms these will be discussed. The
      prevalence of fatigue in cancer patients will then be documented. An overview of
      what is currently understood about fatigue in cancer will follow. Based on the
      literature, conceptual and methodological difficulties will be described.
      Finally, gaps in understanding will be identified. Suggestions for future
      research will be formulated and potential interventions to decrease feelings of
      fatigue explored.

PMID- 7620652
TI  - A research and journal club: a medium for teaching, professional development and
      networking.
AB  - The establishment of a monthly Radiography Research and Journal Club has helped
      to meet the educational and professional development needs of students and
      qualified staff in a changing teaching and learning environment. The introduction
      of degree education presented opportunities for new, student centred learning
      styles within the pre-registration therapeutic radiography course offered by The
      Royal Marsden NHS Trust and Kingston University. At the same time the need to
      provide a forum for academic and clinical staff to learn about the research
      process in general and current work in radiography and oncology in particular was
      recognized. A varied, and practitioner-led, programme for the Club and a flexible
      approach ensures maximum participation. The review of a journal article about
      telephone counselling for cancer patients and the ensuing discussion is given as
      an example of the value of one such meeting. The topic raised issues related to
      current practice and the research methods used provoked a number of questions. As
      the result of the discussion two of the participants are involved in a research
      project on a related issue.

PMID- 7620653
TI  - Quality assurance in palliative care: some of the problems.
AB  - This review considers some of the difficulties associated with quality assurance
      in the context of palliative care. In particular, it will focus on the key
      question of who should be responsible for assessing quality and the problems of
      over-reliance on one particular perspective. Problems encountered in formulating
      criteria, setting standards and developing outcome measures, many of which are
      exacerbated in the palliative care setting, are discussed. A review of some of
      the methods currently available for assessing quality and their limitations are
      delineated. Finally, attention is drawn to some of the practical and
      methodological difficulties currently confronting palliative care with regard to
      quality assurance.

PMID- 7620654
TI  - A randomized cross-over study of the efficacy of codeine phosphate versus
      Ispaghulahusk in patients with gynaecological cancer experiencing diarrhoea
      during pelvic radiotherapy.
AB  - Diarrhoea is the commonest acute complication during radiotherapy treatment to
      the pelvis. Codeine phosphate and a low residue diet is the standard therapy for
      radiation-induced diarrhoea at The Royal Marsden NHS Trust. The hypothesis put
      forward was that Ispaghulahusk and codeine phosphate were equally effective in
      the treatment of diarrhoea during radiotherapy. Participants in the study were
      female patients who had experienced change of bowel habit whilst receiving
      radiotherapy for their gynaecological cancer. Quantitative data was collected
      from patient diaries and treatment flow-sheets. Ten patients were randomized into
      the trial, five to codeine phosphate, and five to Ispaghulahusk. Continuing the
      trial was questioned after 10 patients had been treated. All five patients in the
      codeine phosphate arm received adequate control, while the five patients
      allocated to the Ispaghulahusk arm were all crossed-over to codeine phosphate
      with resolution of their diarrhoea. The results show that Ispaghulahusk, whilst
      not totally ineffective at controlling diarrhoea, was significantly less
      effective than codeine phosphate. Our conclusion is that there is insufficient
      reason to change to a less effective and less palatable preparation for the
      control of radiation-induced diarrhoea.

PMID- 7620655
TI  - 1995-2005 the second decade of health service reform.

PMID- 7620656
TI  - The equity debate within the British National Health Service.
AB  - This paper begins by identifying the principles of equity and fairness on which
      the British National Health Service (NHS) was founded in 1948. It then goes on to
      summarize the viewpoints of those who more recently have argued that equity is an
      out-moded, utopian and unachievable concept that should not be applied to the
      delivery of health care services. A brief review is conducted of the definitions
      of equity and inequity as these apply to health care. Brief attention is paid to
      the relationship between equitable distribution of health care and social class.
      The new contemporary significance of equity for all NHS managers is exposed
      through a debate concerning the impact of the recently introduced policies for
      the implementation of a quasi-market in health services in Britain. The
      inseparable relationship between equity and the rationing of resources is
      identified as central to the just distribution of health care. The paper presents
      evidence that the quasimarket solutions to improved economic efficiency and cost
      containment are often in direct conflict with the equity doctrine on which the
      NHS was created. A brief conclusion how equity principles might be restored to
      health policy is proffered.

PMID- 7620657
TI  - Planning for continuity of carer in nursing.
AB  - The introduction of primary nursing and the named nurse reflects a growing
      recognition of the importance of continuity of carer in nursing rather than
      simply continuity of care. Continuity of carer is fundamental to the development
      of therapeutic inter-personal relationships with patients. Hospital nursing,
      however, provides a 24-hour service and therefore continuity of carer must be
      maintained within a system of nurse substitution. This paper identifies some of
      the organizational tensions experienced by nurses attempting to promote
      continuity of carer within a nursing development unit that is simultaneously
      striving to offer nurses personal development opportunities.

PMID- 7620658
TI  - Professional expectations and activities of nurses in Israel.
AB  - A total of 159 nurses participating in study days throughout Israel responded to
      a questionnaire on professional expectations and activities. Their age ranged
      from 26 to 73; 66% received their basic nursing education in diploma schools for
      registered nurses, but 36.5% had completed or were studying towards a post-basic
      baccalaureate degree in nursing and 23.2% were studying towards or had completed
      a master's degree. The highest percentage of respondents--92% expected to be
      involved much and very much in clinical decision-making. The professional
      activity most nurses were involved in (86.8%) was 'professional reading'.
      Multiple stepwise regression showed that continuing education explained 25.9% of
      the variance of professional activities. No satisfactory explained variance was
      achieved on professional expectations. In this convenience sample the percentage
      of academic nurses was higher than in the working force in Israel.

PMID- 7620660
TI  - Skill-mix in nursing: efficiency and quality?

PMID- 7620659
TI  - Outcome measures: problems and opportunities for public health nursing.
AB  - Increasingly, outcome measures are being used to evaluate the effectiveness of
      health care. There are particular difficulties in establishing outcome measures
      for public health nursing, especially those that would demonstrate health gain.
      These problems arise as a result of the role of public health nursing and the
      nature of outcome measures. Possible solutions are the use of caseload and
      community profiles or the aggregation of client-negotiated health objectives.
      These solutions would also provide small area health information and outcome
      measures which would be sensitive to health needs in local communities.

PMID- 7620661
TI  - Developing care plan documentation: an action research project.

PMID- 7620662
TI  - The management of memory deficits in the elderly: the nurses' role.

PMID- 7620663
TI  - Bonding theory--tying mothers in knots? A critical review of the application of a
      theory to nursing.
AB  - In recent times, nursing has witnessed a growing support for the notion of theory
      as being instrumental in enhancing nursing practice and ultimately patient care
      (Marriner, 1986). Whether generated from nursing practice, or 'borrowed' from
      other fields, the use of theory is viewed by some as the key to the ultimate
      recognition of nursing as a scientific, professional discipline in its own right
      (Stevens, 1984). Parallel to this view, there is a research perspective that
      questions the ultimate contribution of certain theories to health-care practice,
      particularly those emanating from other disciplines, urging caution in their
      practical utility. This paper enlarges upon this theme, focusing specifically
      upon the psychological theory of bonding, attempting to explore critically the
      degree to which it can be used in nursing practice, and to which it contributes
      towards our understanding of the attachment behaviour between a mother and her
      infant. A brief outline is given of the theory and its impact on health-care
      practice, and possible limitations discussed with reference to the conceptual
      origins of bonding theory, the validity of its research methodology, and its use
      within the wider health-care setting. A feminist sociological perspective is used
      in a brief attempt to explore the wider implications of the bonding theory in
      relation to the position of women.

PMID- 7620664
TI  - Incidence and prevalence of lymphoedema: a literature review.
AB  - Lymphoedema is a significant health problem for some groups of patients and few
      health authorities have carried out a systematic health needs assessment for this
      client group. When planning and developing services, there is a need to
      demonstrate a knowledge of the literature relating to the incidence and
      prevalence of this condition. To facilitate interpretation of the literature,
      clarification of the difference between incidence and prevalence rates is
      included in this review. It is important that the differences between these rates
      is clearly understood when considering the nature of a chronic, progressive
      condition. The problems inherent in comparing results from studies which use
      different definitions of what constitutes 'lymphoedema', as well as different
      methods of measurement are acknowledged. A number of studies are examined and
      using information from this review, it is suggested that the prevalence rate of
      lymphoedema in women treated for breast cancer is in the region of 25-28%.
      Factors which influence the development of lymphoedema, and the controversy
      concerning axillary node sampling and dissection are discussed. The need to
      consider patients with lymphoedema due to very advanced cancer, and those with
      lower limb problems is also highlighted.

PMID- 7620665
TI  - Gynopia in nursing practice: the case of urethral catheterization.
AB  - A pilot study of catheterized women was designed to investigate their perceptions
      of pain and discomfort during the procedure. The study aimed to test the
      feasibility of conducting a larger randomized controlled trial. Problems were
      encountered during the execution of the study, due to the need to conform to
      established principles in clinical research. Restrictions on access to patients
      impinged upon the opportunity to 'cast the net wide' in order to generate
      meaningful data.

PMID- 7620666
TI  - An exploration of the communication that takes place between nurses and patients
      whilst cancer chemotherapy is administered.
AB  - Existing studies indicate the importance of the communication that takes place
      within specific nursing procedures, but a body of knowledge in this area has yet
      to be developed. This study explores the verbal communication that took place
      when nurses were administering cytotoxic chemotherapy in a specialized
      gynaecological oncology unit. Most interactions were initiated by the nurses and
      concentrated on information giving. Detailed, clear and precise explanations were
      provided, reflecting the highly technical nature of the procedure. The nurses
      rarely made any assessment of the patients' understanding of the situation, their
      preconceptions, or their feelings. It is suggested that there is a need to
      structure and improve the emotional, supportive, and information-giving
      techniques employed by nurses.

PMID- 7620668
TI  - A model for research-based practice.
AB  - Nursing practice is based on experience, tradition, intuition, common sense,
      untested theory and sometimes research. There are a number of reasons why nurses
      may see research as irrelevant to their practice. This paper provides a model
      identifying possible strategies to help nurses develop research-based practice.

PMID- 7620667
TI  - A service evaluation of stoma care nurses' practice.
AB  - Stoma care nurses aim to meet the physical, psychological, social and spiritual
      needs of patients. Development of stoma care nursing services has varied, as it
      has been the responsibility of each nurse, resulting in differences in the mode
      of delivery. This qualitative and quantitative study involved stoma care nurses
      from six areas in Essex, to assess patient perception of the service they
      received. Overall, the satisfaction level was high despite differences in
      delivery of care especially timing and frequency of visits at home.

PMID- 7620669
TI  - The potential of the professional portfolio for nursing.
AB  - Professional profiles and portfolios have recently been identified by nursing's
      regulatory bodies in the UK as ways of recording each nurse's career and
      professional development. Although the use of portfolios is widespread in
      education, the concept of a developmental portfolio to support continuing
      professional development on an individual basis is recent. As an innovation in
      nursing the portfolio is to be used for periodic registration with the UK Central
      Council (UKCC), for the on-going recording of learning, both formal and
      experiential, and as a way of accrediting prior learning for academic purposes.
      This paper argues that the potential of the portfolio is wider than the purposes
      already identified in that the knowledge generated from experiential learning and
      identified by reflective practice is of specific interest and value to the
      nursing profession as a whole. In particular portfolios are likely to record the
      knowledge embedded in practice, which is often hard to describe, yet represents
      nursing's expertise. For this potential to be realized pragmatic issues such as
      finance, time and verification of experiences need to be addressed, and an
      infrastructure created to support the nurse compiling the profile.

PMID- 7620672
TI  - Caring for a mentally ill relative: the burden for the family.

PMID- 7620671
TI  - An exploration of the perceptions of caregiving and caring responsibilities in
      Chinese families.

PMID- 7620670
TI  - The management of diabetes in adolescents and young adults: a preliminary case
      study.
AB  - This paper describes one part of a first-stage study concerned with the care
      received by a group of adolescents and young adults with insulin-dependent
      diabetes mellitus (IDDM) in one district health authority. The paper reports
      findings from a self-selected sample of 30 patients aged between 15 and 25. Each
      of the 30 patients was interviewed during a routine appointment at a diabetes
      clinic. The patients' doctor at the clinic and one of the diabetes specialist
      nurses also filled in a short questionnaire for each of the patients interviewed.
      The main finding was that although all 30 patients interviewed reported that
      their diabetes control was at least moderately good, a significant number of
      patients had blood glucose levels above the recommended norm. The study lends
      support to the widely held belief that young adults with diabetes have particular
      difficulties in maintaining blood glucose levels within a normal range. It is
      suggested that processes within the current mode of care may be contributing to
      this poor level of control. Recommendations for a controlled trial of specialist
      nurse versus doctor care are made.

PMID- 7620673
TI  - [The practice of nursing in the countries of the European Community. An empirical
      study].

PMID- 7620674
TI  - [In spite of capping of costs and reduction of beds hospitals expect billion
      deficits].

PMID- 7620675
TI  - [Quality assurance is the non-word of the year 1995].

PMID- 7620676
TI  - [Treatment by natural remedies as a supportive measure. Bandages and compresses
      as supplemental measures to drug therapy].

PMID- 7620677
TI  - [Reduction of antipyretics. A gentler way to reduce fever with lemon compresses
      along with administration of paracetamol].

PMID- 7620679
TI  - [Psychotropic drugs for the aged].

PMID- 7620678
TI  - [In our facility nobody dies alone].

PMID- 7620680
TI  - [Gerontopsychiatric day care facilities. Part-hospital care of aged patients with
      mental disorders].

PMID- 7620681
TI  - [Appropriate behavior in crisis situations. Violence--what to do?].

PMID- 7620682
TI  - [Work in nursing education guided by theory].

PMID- 7620683
TI  - [The integration of health promotion into the guiding image of nursing].

PMID- 7620684
TI  - [Chaplaincy and social services at the St. Josef Hospital in Moers].

PMID- 7620685
TI  - [Reader poll. 2. What some demand is rejected by others].

PMID- 7620686
TI  - In vivo assessment of the atrophogenic potency of mometasone furoate, a newly
      developed chlorinated potent topical glucocorticoid as compared to other topical
      glucocorticoids old and new.
AB  - Topical glucocorticoids still belong to the most important medications available
      in dermatotherapy. The clinical use of topical glucocorticoids, however, nowadays
      is limited by the fear of side-effects both systemic and local, especially skin
      atrophy. The purpose of this study was to assess the atrophogenicity potential of
      newly developed topical glucocorticoids which were said to show an increased
      benefit-risk ratio. The test preparations comprised mometasone furoate, the
      corresponding vehicle, prednicarbate and hydrocortisone. They were applied once
      or twice daily for 6 weeks in healthy volunteers. Skin thickness was assessed
      weekly by using high frequency pulsed ultrasound. Clinically, none of the
      volunteers showed any sign of overt skin atrophy. Skin thickness, however, was
      reduced to a certain extent with all trial preparations including the base
      preparation. As to be expected from previous experiments the results for
      hydrocortisone and prednicarbate did not differ significantly from the ones for
      the base preparation. Interestingly, the same applied to mometasone furoate.
      These findings, together with the other available data, give evidence of an
      increased benefit-risk ratio as compared to previous medium potent topical
      glucocorticoids. This might be of particular interest facing psoriasis vulgaris
      where an antiproliferative activity of a drug is needed.

PMID- 7620687
TI  - Hemodynamic effects of extracardiac drugs.
AB  - Almost all types of drugs which primarily exert extracardiac effects may cause
      adverse cardiovascular reactions. This may apply to such frequently prescribed
      drugs as antihistamines, antidepressants and neuroleptic agents, antibiotics,
      lipid lowering drugs, and many others. Negative chronotropic, inotropic or
      dromotropic effects, changes in pre- and afterload with a decrease in stroke
      volume and cardiac output, or the occurrence of cardiac arrhythmias have all been
      reported upon treatment with extracardiac drugs. Physicians mostly fail to
      consider that these adverse events may well be related to drug effects, but
      rather ascribe them to the underlying disease or variations in the course of the
      patient's illness. Recent characteristic examples of the cardiovascular effects
      of extracardiac drugs are the cardiac arrhythmias (torsades de pointes) caused by
      the H1-receptor antagonists terfenadine and astemizole. These observations were
      made only many years after the availability of these drugs on the market-- in
      some countries even as over-the-counter drugs. In general, both the number of
      drugs causing undesired cardiac events and the different types of adverse
      cardiovascular reactions ascribable to these drugs appear to be on the increase.

PMID- 7620688
TI  - Antianginal effect of transdermal nitroglycerin and oral nitrates given for 24
      hours a day in 2,456 patients with stable angina pectoris. The Italian
      Multicenter Study.
AB  - The effect of transdermal and oral nitrates on anginal symptoms were compared in
      a randomized trial of 2,456 out-patients with stable angina pectoris recruited in
      206 cardiological centers in Italy. Half of the patients had effort-induced
      angina, 12% rest angina and 38% "mixed angina". Before enrollment, all of the
      patients were on stable treatment with oral nitrates either as monotherapy or in
      combination with other antianginal agents. After a 2-week run-in period on the
      previous oral nitrate regimen, two thirds of the patients were randomized to
      receive a nitroglycerin patch 5 mg/24 hours for 2 weeks, the remaining one third
      continued their previous treatment. The patients subsequently reporting > or = 1
      anginal attack/2 weeks were titrated to transdermal nitroglycerin 10 mg/24 hours
      or to the maximum dose of oral nitrates suggested by the manufacturer for the
      following 4 weeks; asymptomatic patients continued on the initial dosages. The 2
      week anginal attack rate was reduced from 4.9 +/- 5.3 to 1.4 +/- 2.5 in the
      transdermal nitroglycerin group (-71%), and from 4.5 +/- 4.7 to 1.5 +/- 2.7 (
      67%) in the oral nitrate group. The proportion of patients free of angina
      increased from 12% to 54% (+343%) with transdermal nitroglycerin and from 15% to
      49% with oral nitrates (+218%) (p < 0.05). The reduction in angina frequency was
      similar during the day and during the night. Nocturnal angina was rare in
      patients with effort angina. However, about half of the patients with rest and
      "mixed" angina had had nocturnal episodes, the number of which was significantly
      reduced by both regimens: nighttime asymptomatic patients increased from 45% to
      82% in the rest angina group, and from 50% to 83% in the "mixed" angina group,
      with no differences between treatments. Withdrawals due to side-effects were
      rare: 1.5% with transdermal nitroglycerin and 1.3% with oral nitrates. Headache
      was the most common side-effect and was more frequently reported with oral
      nitrates. Although the lack of a placebo control precludes an absolute evaluation
      of efficacy, the results of the present study suggest that both transdermal
      nitroglycerin and oral nitrates may provide relief of anginal symptoms over 24
      hours in the majority of stable angina patients. Nocturnal angina, reported by
      50% of the patients with rest and mixed angina, is effectively reduced by the
      administration of nitrates over 24 hours.

PMID- 7620689
TI  - Oral therapy with flurithromycin in ear, nose and throat infections.
AB  - In this study efficacy and tolerability of flurithromycin ethylsuccinate (FE)
      were evaluated in ear, nose and throat infections. One hundred and three patients
      were treated with FE tablets 375 mg 12-hourly for a mean duration of treatment of
      8.2 days and they were divided into groups according to the pathology:
      pharyngitis/tonsillitis (chronic 7, acute 38), rhinosinusitis (chronic 7, acute
      12), otitis (chronic 6, acute 32) and sialadenitis (acute 1). Patients evaluable
      for clinical efficacy were 101, among them a complete recovery was registered in
      88.2%, an improvement in 9.9% and a treatment failure in 1.9%. Bacteriological
      evaluation was possible in 95 patients, showing the eradication of the pathogen
      in 94.7%. Tolerability was judged to be excellent in 81.6%, good in 15.5% and
      discrete in 2.9%. These results demonstrate that FE is safe and effective in the
      treatment of infections established on acute or chronic inflammatory states.

PMID- 7620690
TI  - Successful management of female office workers with "repetitive stress injury" or
      "carpal tunnel syndrome" by a new treatment modality--application of low level
      laser.
AB  - Female office workers with desk jobs who are incapacitated by pain and tingling
      in the hands and fingers are often diagnosed by physicians as "repetitive stress
      injury" (RSI) or "carpal tunnel syndrome" (CTS). These patients usually have poor
      posture with their head and neck stooped forward and shoulders rounded; upon
      palpation, they have pain and tenderness at the spinous processes C5-T1 and the
      medial angle of the scapula. In 35 such patients we focused the treatment
      primarily at the posterior neck area and not the wrists and hands. A low level
      laser (100 mW) was used and directed at the tips of the spinous processes C5-T1.
      The laser rapidly alleviated the pain and tingling in the arms, hands and
      fingers, and diminished tenderness at the involved spinous processes. Thereby, it
      has become apparent that many patients labelled as having RSI or CTS have
      predominantly cervical radicular dysfunction resulting in pain to the upper
      extremities which can be managed by low level laser. Successful long-term
      management involves treating the soft tissue lesions in the neck combined with
      correcting the abnormal head, neck and shoulder posture by taping, cervical
      collars, and clavicle harnesses as well as improved work ergonomics.

PMID- 7620691
TI  - Clinical rationale for the use of an ultra-short acting beta-blocker: esmolol.
AB  - Esmolol is a unique cardioselective, intravenous, ultra-short acting, beta
      adrenergic blocking agent. A 9-minute half-life with rapid clinical onset and
      offset of action and the ability to titrate the drug to changing circumstances
      makes esmolol a useful addition to our treatment armamentarium. The efficacy and
      safety of esmolol have been shown in specific clinical settings, i.e. in patients
      with unstable angina, myocardial infarction, atrial fibrillation or flutter and
      supraventricular tachycardia. In the emergency management of hypertension,
      tachycardia or arrhythmia in critical care units, emergency room and surgery,
      esmolol is effective by attenuating hemodynamic responses from sympathetic
      activation or endogenous catecholamine release. With careful titration and
      monitoring of the patient, esmolol is relatively safe in the management of
      hypertension or tachyarrhythmias associated with congestive heart failure or
      chronic obstructive lung disease where beta-blockers are otherwise
      contraindicated. Different dosage schedules have been employed as per the
      clinical setting and the diagnosis. Generally, esmolol is infused intravenously
      in doses ranging from 25-300 micrograms/kg/min, along with a loading dose or
      bolus. The most frequently reported adverse effect associated with esmolol
      infusion was hypotension. Adverse effects due to beta-blockade can be corrected
      by down-titrating or discontinuing the infusion with complete disappearance of
      clinical effects in 20-30 minutes. Therefore, as an ultra-short acting beta
      blocker, esmolol is an important therapeutic option in the acute clinical
      setting.

PMID- 7620692
TI  - Signalling drug-induced rash with 36 drugs recently marketed in the United
      Kingdom and studied by Prescription-Event Monitoring.
AB  - This study examines skin rash, as a reported event, in the patients who used one
      of the 36 drugs recently released to the UK market and studied by Prescription
      Event Monitoring between 1985 and 1992. The results are also compared to the
      voluntary reports on rash as a possible adverse drug reaction sent to the
      Committee on Safety of Medicines (CSM). Specific types of skin rash (e.g.
      exfoliative dermatitis) are excluded. The rate of rash has been calculated for 2
      periods, the first month (T1) and the subsequent 5 months (T2) after the first
      prescription for the drug. Despite the heterogeneity of the patient groups, the
      rate for rash between the 2nd and 6th months was consistent in the 36 drugs and
      probably represented the baseline rate of rash due to a variety of nonspecific
      causes. This rate (T2) was around 1 per 1,000 patients per month (ranging from
      0.5 to 2 per 1,000 patients per month). On the other hand, in the first month
      after the first prescription for the drug, the rate (T1) varied substantially
      from 0.9 to 6.4 per 1,000 patients per month. Diltiazem had the highest first
      monthly rate. These rates are listed for the 36 drugs. The difference of the
      rates was tested by 2 methods: a standard statistical test assuming a Poisson
      model and a method based on the ratio of the rates for the 2 periods. When the 2
      rates (T1 and T2) were similar to each other, drug induced rash was considered to
      be rare.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7620693
TI  - A dose-ranging study of labetalol in moderate to moderately severe hypertension.
AB  - Labetalol optimal doses for Indonesian patients were investigated in an open,
      multicentre, unforced titration dose-finding study involving 134 essential
      hypertensive outpatients with baseline supine DBP (SuDBP) of 105-129 mmHg.
      Labetalol was started at 50 mg bid and as necessary increased by 50 mg bid every
      2 weeks. Evaluable for efficacy were 105 moderate and 25 moderately severe
      hypertensives. Labetalol was effective (decreased SuDBP to 90 mmHg or less) in
      75% of patients and moderately effective (decreased SuDBP at least 10% of
      baseline but did not reach 90 mmHg) in 10%. The cumulative percent responders
      were 15, 49, 79 and 85% to final daily doses of 100, 200, 300 and 400 mg,
      respectively. Adverse reactions were found in 31% of patients, the most frequent
      were gastrointestinal complaints causing 3 withdrawals. It is concluded that
      labetalol optimal doses for Indonesian moderate to moderately severe
      hypertensives range from 100 to 300 mg daily in 2 divided doses.

PMID- 7620694
TI  - Comparative bioavailability of metronidazole formulations (Vagimid) after oral
      and vaginal administration.
AB  - Bioavailability of Vagimid 500 tablets (film coated, 500 mg metronidazole) and
      absorption of metronidazole into the systemic circulation after vaginal
      administration of Vagimid vaginal tablets (100 mg metronidazole) relative to
      respective listed references were studied in 16 female healthy volunteers (age 21
      37 years, weight 45-67 kg, height 158-179 cm). Metronidazole and its main
      hydroxylated metabolite were measured using an HPLC-method with detection limits
      of 0.025 and 0.25 micrograms/ml (for vaginal and oral studies), respectively.
      Extent of absorption was assessed by AUC0-infinity (bioequivalence range 0.80
      1.25), rate of absorption by Cmax/AUC0-infinity (bioequivalence range 0.70-1.43).
      Geometric means and 90%-confidence intervals of the ratios of these primary
      characteristics were calculated using a multiplicative model. Vagimid 500 tablets
      were bioequivalent to the reference formulation with regard to extent and rate of
      absorption of metronidazole because of AUC0-infinity = 0.995 (0.84-1.18) and
      Cmax/AUC0-infinity = 1.11 (0.94-1.30). The absorption of metronidazole into the
      systemic circulation after vaginal administration of Vagimid vaginal tablets
      caused maximal serum concentrations between 433 and 1,156 ng/ml after 8-20 h
      which are bactericidal only for the most susceptible anaerobic germs and which
      are most likely only of marginal importance for drug safety.

PMID- 7620695
TI  - Clinical evaluation of bevantolol hydrochloride in patients with severe
      hypertension. The Cooperative Study Group on Bevantolol in Japan.
AB  - The clinical efficacy and safety of bevantolol hydrochloride, a newly developed
      beta-blocker, used in combination with other types of antihypertensive agents,
      were evaluated in patients with severe hypertension by multicenter open-label
      trials. A total of 28 patients were studied at 20 medical centers. Four patients
      (14.3%) were excluded for some reasons, and the remaining 24 patients (22
      outpatients and 2 inpatients) were analyzed. Following the initiation of therapy,
      blood pressure decreased from 181 +/- 15 (SD)/114 +/- 3 mmHg to 170 +/- 17/102 +/
      8 mmHg (p < 0.01) on the 14th day of the therapy and gradually lowered further
      thereafter. At the end of the trial (8th week), blood pressure was stabilized at
      the level of 160 +/- 14/96 +/- 10 mmHg. The antihypertensive efficacy rated by
      the changes in mean blood pressure was 79.2% (19/24). Pulse rate decreased
      slightly but significantly from 75 +/- 10 beats/min to 70 +/- 7 (p < 0.05) on the
      14th day of the therapy and stabilized at the similar level thereafter. As
      abnormal laboratory data were detected in 3 patients and 1 patient complained of
      a mild headache, the safety ratio was 83.3% (20/24 patients). When the usefulness
      was assessed in terms of antihypertensive efficacy and safety profiles,
      bevantolol hydrochloride was considered useful in 75.0% of the patients studied.
      In conclusion, bevantolol hydrochloride, used in combination with other classes
      of antihypertensive agents, appears to be an excellent drug for the management of
      patients with severe hypertension.

PMID- 7620696
TI  - The interaction of fluvastatin and cyclosporin A in renal transplant patients.
AB  - A possible interaction between fluvastatin, a new HMG CoA reductase inhibitor,
      and cyclosporin A (CsA) was studied in 16 stable renal transplant patients with
      dyslipoproteinemia despite dietary control. They entered a 12-week study period:
      4-week baseline, 4-week placebo and 4-week fluvastatin treatment (20 mg daily).
      Weekly trough whole blood CsA concentrations were measured by monoclonal antibody
      immunoassay. Serial renal and liver function tests and creatine phosphokinase
      (CPK) were monitored. The mean trough levels of CsA during fluvastatin treatment
      were 115.6 micrograms/l compared with 114.3 micrograms/l and 113.3 micrograms/l
      in the baseline and placebo period, respectively. Apart from a small decrease in
      serum albumin level (from a mean of 38.6 g/l to 37.9 g/l), there were no
      significant changes in renal and liver functions or CPK levels. No adverse
      effects were reported. Fluvastatin (20 mg daily) may be used safely without extra
      monitoring of blood CsA concentrations in renal transplant patients.

PMID- 7620697
TI  - [XXVIII National Congress of the SEPAR (Spanish Society of Pneumology and
      Thoracic Surgery). Valencia, 31 May-4 June 1995. Abstracts].

PMID- 7620698
TI  - Evidence that 5-hydroxytryptamine release in rat dorsal raphe nucleus is
      controlled by 5-HT1A, 5-HT1B and 5-HT1D autoreceptors.
AB  - Electrically stimulated 5-hydroxytryptamine (5-HT) release was monitored in
      slices of rat dorsal raphe nucleus (DRN) by fast cyclic voltammetry. Pseudo
      single pulse stimulations (5 pulses at 100 Hz) were used to enable the effect of
      various receptor agonists to be seen without competition from endogenously
      released transmitter. The selective 5-HT1A receptor agonist, (+)-8-OH-DPAT (1.0
      microM) decreased stimulated 5-HT release to 31 +/- 3% of controls. This decrease
      was inhibited by the 5-HT1A receptor antagonists, (+)-WAY-100135 (1.0 microM) and
      WAY-100635 (0.1 microM) but not by the 5-HT1D/B antagonist, GR127935 (0.05
      microM). The selective 5-HT1B receptor agonist, CP-93129 (0.3 microM) decreased
      stimulated 5-HT release to 61 +/- 4% of control. This effect was antagonized by
      the 5-HT1B receptor antagonist, isamoltane (0.5 microM) but not by (+)-WAY
      100135. The 5-HT1D agonist, sumatriptan (0.5 microM) decreased stimulated 5-HT
      release to 52 +/- 2% of controls. This decrease was blocked by GR-127935 but not
      by WAY-100635. These results suggest that 5-HT release in the rat DRN is under
      the control of 5-HT1A, 5-HT1B and 5-HT1D autoreceptors.

PMID- 7620699
TI  - Endothelin ETA and ETB mRNA and receptors expressed by smooth muscle in the human
      vasculature: majority of the ETA sub-type.
AB  - 1. We measured the ratio of ETA and ETB sub-types in the media (containing mainly
      smooth muscle) of human cardiac arteries (aorta, pulmonary and coronary),
      internal mammary arteries and saphenous veins. 2. In saturation experiments,
      [125I]-endothelin-1 ([125I]-ET-1) bound with high affinity to the media of each
      vessel (n = 3 individuals or homogenate preparations +/- s.e. mean): coronary
      artery, KD = 0.14 +/- 0.02 nM, Bmax = 71.0 +/- 21.0 fmol mg-1 protein; pulmonary
      artery, KD = 0.85 +/- 0.25 nM, Bmax = 15.2 +/- 10.3 fmol mg-1 protein; aorta, KD
      = 0.51 +/- 0.02 nM, Bmax = 9.4 +/- 4.4 fmol mg-1 protein; internal mammary
      artery. KD = 0.34 +/- 0.31 nM, Bmax = 2.0 +/- 0.5 fmol mg-1 protein and saphenous
      vein, KD = 0.28 +/- 0.05 nM, Bmax = 52.8 +/- 1.0 fmol mg-1 protein. In each
      vessel, over the concentration-range tested, Hill slopes were close to unity and
      a one site fit was preferred to a two site model. 3. In competition binding
      assays, the ETA selective ligand, BQ123 inhibited the binding of 0.1 nM [125I]-ET
      1 to the media in a biphasic manner. In each case, a two site fit was preferred
      to a one or three site model: coronary artery, KDETA = 0.85 +/- 0.03 nM, KDETB =
      7.58 +/- 2.27 microM, ratio = 89:11%; pulmonary artery, KDETA = 0.27 +/- 0.05 nM,
      KDETB = 24.60 +/- 5.34 microM, ratio = 92:8%; aorta, KDETA = 0.80 +/- 0.40 nM,
      KDETB = 2.67 +/- 2.60 microM ratio = 89:11%; saphenous vein, KDETA = 0.55 +/-
      0.17 nM, KDETB = 14.4 +/- 0.26 microM, 85:15% (n = 3 individuals or homogenate
      preparations +/- s.e. mean). BQ123 showed up to 18000 fold selectivity for the
      ETA over the ETB sub-type. The ETA-selective ligand, [125I]-PD151242 labelled 85%
      of the receptors detected by a fixed concentration of [125I]-ET-1 in media of
      internal mammary artery, measured by quantitative autoradiography. In contrast,
      the density of ETB receptors detected with [125I]-BQ3020 was 7.0 +/- 1.5 amol mm
      2, representing about 8% of [125I]-ET-1. 4. A single band corresponding to the
      expected position for mRNA encoding the ETA receptor (299 base pairs) was found
      in the media in each of the five vessels (n = 3 individuals) using reverse
      transcript as epolymerase chain reaction assays. A single band corresponding to
      the ETB sub-type (428 base pairs) was also always detected.5. 35S-labelled
      antisense probes to ETA and ETB hybridised to the media of epicardial coronary
      arteries as well as intramyocardial vessels, confirming the presence of mRNA
      encoding both sub-types in the vascular smooth muscle of the vessel wall.6
      Although mRNA for both receptors was detected, competition binding using BQ123
      demonstrated that the majority (at least 85%) of ET receptors present in smooth
      muscle are the ETA sub-type. These results provide further support for the
      hypothesis that the ETA sub-type is the receptor that must be blocked in humans
      to produce a beneficial vasodilatation in pathophysiological conditions where
      there is an increase in peptide concentration or receptor density.

PMID- 7620700
TI  - Pharmacology of LR-B/081, a new highly potent, selective and orally active,
      nonpeptide angiotensin II AT1 receptor antagonist.
AB  - 1. The pharmacological profile of LR-B/081, (methyl 2-[[4-butyl-2-methyl- 6-oxo-5
      [[2'-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]-1(6H)- pyrimidinyl]methyl]-3
      thiophenecarboxylate), a novel antagonist at the angiotensin II (AII) AT1
      receptor, was studied in vitro and in vivo. 2. In rabbit aortic strips incubated
      with LR-B/081 (1-1,000 nM), the concentration-response curve to AII was displaced
      to the right in a nonparallel fashion and the maximal contraction was
      progressively reduced, indicating that the compound is an insurmountable
      antagonist in this preparation (apparent pKB = 9.50 +/- 0.23). However, the
      interaction of LR-B/081 with AII receptors was found to be reversible, since the
      maximal response to AII was restored by coincubation with losartan, a
      surmountable AII AT1-antagonist. Contractions elicited by KCl or phenylephrine
      were not affected by 10 microM LR-B/081. 3. In rat isolated perfused kidney, LR
      B/081 and losartan antagonized the AII-induced vasoconstriction [IC50 (95%
      confidence limits) = 17(13-24) and 39(32-54) nM, respectively]. The LR-B/081
      antagonism was incompletely reversed by excess AII, while losartan was fully
      displaced. The IC50 values of LR-B/081 and losartan obtained against
      vasoconstriction induced by endothelin-1 and noradrenaline were two orders of
      magnitude higher. 4. In pithed rats, the intravenous administration of LR-B/081
      (0.2-2 mumol kg-1) dose-dependently shifted to the right in a nonparallel fashion
      the dose-pressor response curve to AII. The maximal pressor response to AII was
      reduced by LR-B/081 in a dose-dependent fashion. The coadministration of losartan
      induced a progressive recovery of the maximal pressor response to All, indicating
      that in vivo the interaction of LR-B/081 with All receptors is reversible. LR
      B/081 at 6 micromol kg-1, i.v. also did not affect the vasopressor response
      induced by noradrenaline in the pithed rat.5. In conscious normotensive rats,
      single oral administration of LR-B/081 at 6 micromol kg-1 markedly inhibited the
      All-induced pressor response; the inhibition lasted more than 24 h.6. In
      conscious renal hypertensive rats, intravenous LR-B/081 appeared as potent as
      losartan (ED40mmHg(95% confidence limits) = 0.50(0.36-0.70) and 0.86(0.57-1.3)
      micromol kg-1, respectively). A single intravenous(2 micromol kg-1) or oral (6
      micromol kg-1) administration of LR-B/081 induced a marked fall in blood pressure
      which lasted for at least 12 h.7. In conscious spontaneously hypertensive rats,
      LR-B/081 at 20 micromol kg-1 , p.o., induced a marked and sustained fall in blood
      pressure. The duration of the antihypertensive effect was longer than 12 h.Heart
      rate was not modified by LR-B/081 treatment. Repeated oral administration of 17
      micromol kg-1LR-B/081 for 16 days did not result in the development of
      tolerance.8 These results demonstrate that LR-B/081 is a potent, selective and
      orally active antagonist of All at the AT1-receptor subtype, which markedly
      lowers the blood-pressure in conscious renal and spontaneously hypertensive rats.

PMID- 7620701
TI  - Effects of suramin on contractions of the guinea-pig vas deferens induced by
      analogues of adenosine 5'-triphosphate.
AB  - 1. Adenosine 5'-triphosphate (ATP) and some of its analogues contract the guinea
      pig vas deferens, acting via receptors which have been classified as P2X
      purinoceptors. We have recently shown, however, that the effects of ATP are
      enhanced, rather than inhibited, by the non-selective P2 antagonist, suramin, and
      that this enhancement could not easily be explained in terms of inhibition by
      suramin of the breakdown of ATP. We therefore investigated the effects of suramin
      on contractions induced by ATP analogues, to define the structure-activity
      relationships of the suramin-resistant response. 2. In the absence of suramin,
      the order of potency for ATP analogues was adenosine 5'-(alpha,beta
      methylene)triphosphonate (AMPCPP) = P1,P5-diadenosine pentaphosphate (Ap5A) =
      adenosine 5'-tetraphosphate (Ap4) > adenosine 5'-O-(3-thiotriphosphate) (ATP
      gamma S) = adenylyl 5'-(beta,gamma-methylene) diphosphonate (AMPPCP) > P1,P5
      diadenosine tetraphosphate (Ap4A) > adenosine 5'-O-(2- thiodiphosphate) (ADP beta
      S) > 2-methylthioadenosine 5'-triphosphate (MeSATP) > or = ATP > adenosine 5'
      diphosphate (ADP). This is generally in agreement with previously reported
      structure-activity relationships in this tissue. 3. In the presence of suramin (1
      mM), responses to Ap5A, Ap4A, AMPPCP, ADP beta S and ADP were abolished or
      greatly reduced, and contractions induced by AMPCPP, Ap4 and ATP gamma S were
      inhibited. Contractions induced by MeSATP however, like those induced by ATP
      itself, were not reduced, but at concentrations above 100 microM were enhanced.
      In the presence of suramin (1 mM) the order of potency of analogues was therefore
      AMPCPP = Ap4> ATP = MeSATP> ATP gamma S, with all other analogues tested being
      essentially inactive at concentrations up to 500 microM.4. Contractile responses
      of the vas deferens to transmural nerve stimulation (1-50 Hz) in the presence of
      the alpha-adrenoceptor antagonist, phentolamine (10 microM), were abolished by
      suramin (1 mM). This is in agreement with previous reports that suramin inhibits
      the excitatory junction potential, a response thought to be mediated by P2
      purinoceptors. It is however hard to reconcile the evidence implicating ATP as
      the non-adrenergic transmitter responsible for this response with the failure of
      suramin to inhibit the contractions induced by ATP itself while abolishing nerve
      mediated contractions.5. In conclusion, these results confirm our previous
      findings of a suramin-resistant component to the ATP-induced contraction in the
      guinea-pig vas deferens, and show that the structure-activity relationships of
      this response are not identical to those of any known P2-purinoceptor subclass.
      Although the inhibition by suramin of the breakdown of ATP may contribute to the
      suramin-resistance of some of the ATP analogues, it does not appear to provide
      the full explanation.

PMID- 7620703
TI  - Rapid, agonist-induced desensitization of alpha 2-autoreceptors modulating
      transmitter release.
AB  - 1. The release of previously incorporated [3H]-noradrenaline was investigated in
      cultures of dissociated chick or rat sympathetic neurones and in cerebrocortical
      slices from neonatal or adult rats. Noradrenaline, in the presence of 10 mumol l
      1 of the uptake inhibitor, cocaine, or the selective alpha 2-adrenoceptor
      agonist, 5-bromo-N-(4,5-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine (UK 4,304),
      was applied for different periods of time in order to detect a possible time
      dependence of the alpha 2-adrenoceptor-mediated inhibition of electrically evoked
      tritium outflow. 2. In chick sympathetic neurones, stimulation-evoked overflow
      was reduced to 30%, 42%, or 56% of control when noradrenaline (1 mumol l-1) was
      present for 2, 8, or 16 min, respectively. Likewise, UK 14,304 (1 mumol l-1)
      present for these periods of time reduced 3H overflow to 35%, 51%, and 53% of
      control, respectively. Addition of 1 nmol l-1 to 10 mumol l-1 UK 14,304 for
      either 2 or 16 min did not produce significantly different IC50 values, but the
      inhibitory effects were smaller with 16 min as compared to 2 min exposure at
      concentrations > or = 10 nmol l-1. 3. In rat sympathetic neurones, noradrenaline
      (100 nmol l-1) reduced stimulation-evoked overflow to 33%, 56%, or 57% of
      control, when present for 2, 8, or 16 min, respectively. Addition of UK 14,304 (1
      mumol l-1) for these periods of time caused inhibition to 11%, 41%, and 46% of
      control. Applying UK14,304 for either 2 or 16 min did not result in significantly
      different IC5o values, but the inhibition induced by 16 min as compared to 2 min
      exposure was smaller at concentrations > 10 nmol 1-1.4. In cerebrocortical slices
      from either neonatal or adult rats, exposure to 0.1 to 1.0 micromol 1-1 UK14,304
      for 16 min never caused a smaller inhibition than a corresponding 3 min exposure,
      although various experimental conditions were investigated.5 The results
      demonstrate that alpha 2-adrenoceptors which regulate noradrenaline release from
      sympathetic neurones undergo agonist-induced desensitization within minutes. Such
      rapid desensitization of alpha 2-autoreceptors was not detected in brain slice
      preparations.

PMID- 7620702
TI  - Quantitative comparisons of muscarinic and bradykinin receptor-mediated Ins
      (1,4,5)P3 accumulation and Ca2+ signalling in human neuroblastoma cells.
AB  - 1. Muscarinic and bradykinin receptor-mediated Ins(1,4,5)P3 accumulation, Ca2+
      mobilization and Ca2+ entry have been examined in human SH-SY5Y neuroblastoma
      cells. This has allowed both direct comparison of signalling events by two
      receptor types potentially linked to the same transduction pathway and an
      investigation of the interactions between the components of this pathway. 2.
      Stimulation of muscarinic receptors with carbachol produced biphasic
      accumulations of Ins(1,4,5)P3 consisting of a rapid peak followed by a lower
      sustained phase. Both phases were dose-dependent but the potency of elevation at
      peak was significantly less than that of the sustained phase. Bradykinin also
      dose-dependently stimulated Ins(1,4,5)P3 accumulation but responses were smaller
      and not sustained. 3. Lowering of [Ca2+]e reduced basal Ins(1,4,5)P3 levels. Peak
      Ins(1,4,5)P3 elevation in response to carbachol and bradykinin were lowered by an
      amount approximating this reduction over the entire dose-response curves.
      Sustained Ins(1,4,5)P3 elevation in response to carbachol showed a more marked
      absolute reduction. Agonist potencies were unaffected by lowering [Ca2+]e. Thus,
      a consistent but small amount of PLC activity during rapid activation appears to
      be sensitive to lowered [Ca2+]e, whilst activity during sustained stimulation is
      greatly facilitated by external Ca2+, probably through Ca2+ entry. 4. The
      temporal- and dose-dependency of carbachol-mediated Ins(1,4,5)P3 accumulations
      were unaffected by loading cells with fura-2, thus allowing direct comparison of
      Ins(1,4,5)P3 and [Ca2+]i changes monitored by fura-2. 5. Changes in [Ca2+]i by
      both agonists revealed temporal patterns that were similar to Ins(1,4,5)P3
      accumulations. Only carbachol stimulated a marked sustained [Ca2+]i signal and
      this was fully dependent on external Ca2+. 6. All agonist-mediated [Ca2+]i
      elevations occurred with significantly greater potency than that of the
      respective Ins(1,4,5)P3 accumulations. Further examination of peak elevations in
      response to carbachol indicated that this was independent of Ca2+ entry. Thus, a
      major site for amplification of the potency of rapid agonist-mediated responses
      lies at the level of the Ins(1,4,5)P3 receptor. 7. The transient nature of
      Ins(1,4,5)P3 and [Ca2+]i peaks followed by either lower but sustained levels with
      carbachol or a return to basal levels with bradykinin suggests rapid but partial
      desensitization of the muscarinic receptor and complete desensitization of the
      bradykinin receptor. This indicates receptor-specific desensitization. Further
      analysis of this was provided by detecting accumulations of [3H]-inositol
      phosphates ([3H]-InsPs) in Li(+)-blocked, myo-[3H]-inositol labelled cells.
      Carbachol produced a rapid accumulation over the first minute, followed by a
      slower linear accumulation for at least 29 min. At this point accumulations were
      dose-related with a potency similar to that of sustained Ins(1,4,5)P3
      accumulation.However, bradykinin produced a minor accumulation of [3H]-InsPs,
      maximal by 1 min. Thus,analysis of PLC activation by measurement of [3H]-InsPs
      over relatively long time frames will indicate the ability of agonists for
      predominantly sustained PLC activation, potentially driven by a partially
      desensitized receptor, as opposed to rapid activation by a fully sensitized
      receptor.8. These data provide quantitative comparisons between and within
      components of the receptor mediated phosphoinositide and Ca2+ signalling pathway,
      provide mechanistic insights into regulation of these components and characterize
      a model system in which heterologous interaction between two receptors linked to
      the same transduction pathway may be examined.

PMID- 7620704
TI  - Modulation by stereoselective inhibition of cyclo-oxygenase of electromechanical
      coupling in the guinea-pig isolated renal pelvis.
AB  - 1. The effects of the (S)- and (R)-enantiomers of the cyclo-oxygenase (COX)
      inhibitor, ketoprofen, have been investigated on the spontaneous activity of the
      guinea-pig isolated renal pelvis and on electrical field stimulation-(EFS)
      induced contractions of the guinea-pig ureter in comparison with the effects of
      the achiral COX inhibitor, indomethacin. 2. (S)-ketoprofen (0.1-100 microM)
      produced a concentration- and time-dependent inhibition of the spontaneous
      myogenic activity of the renal pelvis. The maximal inhibitory effect (%
      inhibition of motility index) averaged 29, 42, 47 and 56% inhibition of control
      values at 0.1, 1, 10 and 100 microM. The (R)-enantiomer was ineffective up to 10
      microM. 3. Indomethacin (0.1-100 microM) likewise produced a concentration- and
      time-dependent inhibition of spontaneous motility of the isolated renal pelvis:
      its maximal inhibitory effect was larger than that produced by (S)-ketoprofen and
      averaged 21, 40, 69 and 95% inhibition of motility index at 0.1, 1, 10 and 100
      microM respectively. In the presence of a maximally effective (100 microM)
      concentration of (S)-ketoprofen, 100 microM indomethacin produced > 90%
      inhibition of residual motility. 4. In the guinea-pig isolated ureter, phasic
      contractions were induced by EFS (5 ms pulse width, 60 V): (S)-ketoprofen (100
      500 microM) had no effect on the EFS-evoked contractions. Indomethacin (100-500
      microM) produced a concentration-dependent inhibition and/or suppression of the
      EFS-evoked contractions. When contraction of the ureter was evoked by 80 mM KCl,
      indomethacin produced about 30 and 80% inhibition at 100 and 300 microM,
      respectively, while (S)-ketoprofen (300 microM) was ineffective. 5. The effect of
      (S)-ketoprofen or indomethacin (10 microM each) on the propagation of myogenic
      impulses along the ureter was determined by use of a three chamber organ bath.
      The renal end of the ureter was electrically stimulated while recording the
      mechanical activity of the renal and bladder ends of the ureter: addition of
      either (S)-ketoprofen or indomethacin (10 microM) did not effect propagation of
      impulses from the renal to the bladder end of the ureter, while nifedipine (10
      microM) promptly blocked the propagated contractions. 6. In sucrose gap
      experiments, (S)-ketoprofen (10-100 microM) produced a time-dependent shortening
      of spontaneous action potentials of the guinea-pig renal pelvis and reduced the
      amplitude and duration of the accompanying phasic contractions. Indomethacin (10
      microM) produced comparable effects on the same parameters and significantly
      reduced the maximal amplitude of depolarization of the pacemaker potential. In
      the presence of 100 microM (S)-ketoprofen, 100 microM indomethacin promptly
      suppressed the residual pacemaker potential and contraction.7. Neither (S)
      ketoprofen nor indomethacin (10 microM each for 60 min) affected the parameters
      of action potential and contraction of the guinea-pig ureter evoked by EFS. Both
      drugs produced a sustained membrane depolarization.8. The present findings
      demonstrate that stereoselective COX inhibition affects pacemaker potentials and
      contractility (electromechanical coupling) in the guinea-pig renal pelvis. The
      modulatory role of endogenous prostanoids involves an amplification of
      electromechanical coupling in the renal pelvis while excitability, contractility
      or propagation of impulses along the ureter appear almost independent of
      prostanoid generation. Previous reports of a total suppression of pyeloureteral
      motility by indomethacin may reflect a combination of COX inhibition and
      nonspecific effect on electromechanical coupling.

PMID- 7620705
TI  - Characterization of [3H]-imidazenil binding to rat brain membranes.
AB  - 1. The binding of [3H]-imidazenil, an imidazobenzodiazepine carboxamide, to rat
      cerebellar membranes was characterized at different temperatures. 2. Specific
      binding was linear with tissue concentrations and reached maximum after 90, 30
      and 5 min incubation at 0, 21 and 37 degrees C, respectively. The binding was of
      high affinity, specific and saturable; non linear regression and Scatchard
      analysis of the data was compatible with the presence of a single population of
      receptor sites with Bmax of 0.74 +/- 0.020, 0.90 +/- 0.011 and 1.0 +/- 0.036 pmol
      mg-1 protein at 0, 21 and 27 degrees C, respectively. Binding affinity decreased
      with increasing temperature: Kd were 0.29 +/- 0.051 nM (0 degrees C), 1.0 +/-
      0.080 nM (21 degrees C) and 2.4 +/- 0.38 nM (37 degrees C). 3. At all tested
      temperatures, [3H]-imidazenil binding was reversible and the Kd calculated from
      the dissociation and association rate constants approximated the equilibrium Kd.
      4. In the presence of gamma-aminobutyric acid (GABA), Kd increased 4 fold at 0
      degrees C, whereas Bmax increased, albeit slightly, at all temperatures. 5.
      Benzodiazepines (BZDs), imidazopyridines and methyl-beta-carboline-3-carboxylate
      (beta CCM) were effective inhibitors of [3H]-imidazenil binding. Conversely,
      GABAA antagonists, barbiturates, picrotoxin and peripheral BZD receptor ligands
      were devoid of any activity. 6. Comparing [3H]-imidazenil to [3H]-flumazenil
      binding in various brain areas, similar densities of recognition sites as well as
      like regional differences in the distribution of binding sites for both
      radioligands were observed (cortex = striatum > cerebellum > spinal cord). 7. The
      present results indicate that [3H]-imidazenil specifically binds to the BZD sites
      of GABAA receptors. Furthermore, the effects of GABA and temperature
      differentiate imidazenil from classicalBZDs. It is suggested that the
      characteristics of imidazenil binding may be relevant to the in vivo pharmacology
      of the drug.

PMID- 7620706
TI  - Ca2+ entry activated by emptying of intracellular Ca2+ stores in ileal smooth
      muscle of the rat.
AB  - 1. The effects of depletion of intracellular Ca2+ stores on muscle tension and
      the intracellular Ca2+ concentration ([Ca2+])i were studied in fura-2 loaded
      longitudinal smooth muscle cells of the rat ileum. 2. After exposure to a Ca(2+)
      free solution, application of Ca2+ caused a small contraction and a rise in
      [Ca2+]i, both of which were potentiated when the muscle was challenged with
      carbachol or caffeine before the addition of Ca2+. 3. Cyclopiazonic acid (CPA), a
      specific inhibitor of sarcoplasmic reticulum Ca(2+)-ATPase, dose-dependently
      decreased tension development and the rises in [Ca2+]i induced by carbachol and
      caffeine in the Ca(2+)-free solution, but conversely increased the Ca(2+)-induced
      responses even in the presence of the voltage-dependent Ca2+ channel blockers,
      methoxyverapamil and nifedipine. 4. The contraction and rise in [Ca2+]i evoked by
      Ca2+ gradually declined with time after removal of CPA, while the reverse was the
      case for the responses to carbachol and caffeine. 5. The Ca(2+)-induced
      contraction and rise in [Ca2+]i in the presence of CPA were inhibited by the
      replacement of Na+ with K+ or Cs+, and by the addition of Cd2+, Ba2+, Ni2+ or
      La3+. 6. The influx of Mn2+ was much greater in extent in the presence of CPA
      than in its absence. 7. These results suggest that the emptying of intracellular
      Ca2+ stores may activate Ca2+ influx not associated with voltage-dependent Ca2+
      channels in the rat ileal smooth muscle.

PMID- 7620707
TI  - Comparison of the pharmacological profile of S-nitrosothiols, nitric oxide and
      the nitrergic neurotransmitter in the canine ileocolonic junction.
AB  - 1. In organ bath experiments, hydroquinone (30-100 microM) and hydroxocobalamin
      (30-100 microM) concentration-dependently inhibited the relaxations induced by NO
      (0.3-30 microM) but not those by nitroglycerin (GTN, 1 microM) in the canine
      ileocolonic junction (ICJ). Hydroxocobalamin reduced the relaxation to low
      frequency (2 Hz) stimulation of the non-adrenergic, non-cholinergic (NANC)
      nerves, whereas hydroquinone only reduced the NANC nerve-mediated relaxations to
      electrical stimulation at 16 Hz, 0.5 ms. 2. Relaxations to S-nitroso-L-cysteine
      (CysNO, 1-30 microM), or S-nitroso-N-acetyl-D,L-penicillamine (SNAP, 1-30 microM)
      were not inhibited by hydroquinone (30-100 microM), hydroxocobalamin (30-100
      microM), pyrogallol (30-100 microM) or L-cysteine (1-3 microM). Hydroquinone (100
      microM) only reduced the relaxation to 10 microM CysNO. Hydroxocobalamin, but not
      hydroquinone, pyrogallol or L-cysteine, potentiated the relaxations to the lowest
      concentration (1 microM) of S-nitrosoglutathione (GSNO, 1-30 microM). 3. In the
      superfusion bioassay, hydroquinone (100 microM) and hydroxocobalamin (1 microM)
      concentration-dependently inhibited the biological activity of authentic NO (1-4
      pmol) to the same extent as that of the transferable nitrergic factor, released
      from the canine ICJ in response to NANC nerve stimulation (8-16 Hz, 2 ms).
      Responses to GTN (10 pmol) or adenosine 5'-triphosphate (10 nmol) were not
      affected. 4. In conclusion, the nitrosothiols CysNO, SNAP and GSNO relax the
      canine ileocolonic junction, but these relaxations, pharmacologically, behave
      differently from the NANC nerve-mediated relaxations. From the bioassay
      experiments, we conclude that the nitrergic factor, released in response to
      NANCnerve stimulation of the canine ICJ, behaves pharmacologically like NO but
      not like a nitrosothiol.Therefore, we suggest NO, and not CysNO, SNAP or GSNO as
      the inhibitory NANC neurotransmitter in the canine ICJ.

PMID- 7620708
TI  - Role of angiotensin converting enzyme in the vascular effects of an endopeptidase
      24.15 inhibitor.
AB  - 1. We investigated the role of angiotensin converting enzyme (ACE) in the
      cardiovascular effects of N-[1-(R,S)-carboxy-3-phenylpropyl]-Ala-Ala-Tyr-p
      aminobenzoate (cFP), a peptidase inhibitor selective for metalloendopeptidase
      (EP) E.C. 3.4.24.15. 2. In conscious rabbits, cFP (5 mg kg-1, i.v.) markedly
      slowed the degradation of [3H]-bradykinin, potentiated the depressor response to
      right atrial administration of bradykinin (10-1000 ng kg-1), and inhibited the
      pressor response to right atrial angiotensin I (10-100 ng kg-1). In each of these
      respects, the effects of cFP were indistinguishable from those of the ACE
      inhibitor, captopril (0.5 mg plus 10 mg kg-1h-1 i.v.). Furthermore, the effects
      of combined administration of cFP and captopril were indistinguishable from those
      of captopril alone. 3. In experimentally naive anaesthetized rats, cFP
      administration (9.3 mg kg-1, i.v.) was followed by a moderate but sustained fall
      in arterial pressure of 13 mmHg. However, in rats pretreated with bradykinin (50
      micrograms kg-1) a more pronounced fall of 30 mmHg was observed. Captopril (5 mg
      kg-1) had similar hypotensive effects to those of cFP, and cFP had no effect when
      it was administered after captopril. 4. CFP displaced the binding of [125I]-351A
      (the p-hydroxybenzamidine derivative of lisinopril) from preparations of rat
      plasma ACE and solubilized lung membrane ACE (KD = 1.2 and 0.14 microM
      respectively), and inhibited rat plasma ACE activity (KI = 2.4 microM). Addition
      of phosphoramidon (10 microM), an inhibitor of a range of metalloendopeptidases,
      including neutral endopeptidase (E.C.3.4.24.11), markedly reduced the potency of
      cFP in these systems. 5. Taken together these findings suggest that the actions
      of cFP in vivo are attributable to inhibition of ACE rather than EP 24.15. Given
      that cFP is a poor inhibitor of ACE in the presence of phosphoramidon in vitro,
      it is likely that cFP is cleaved by a phosphoramidon-sensitive metallopeptidase
      in vivo to liberate N-[1-(R,S)-carboxy-3-phenylpropyl]-Ala-Ala, a potent ACE
      inhibitor.

PMID- 7620709
TI  - Participation of NMDA and non-NMDA excitatory amino acid receptors in the
      mediation of spinal reflex potentials in rats: an in vivo study.
AB  - 1. The effect of various intravenously administered excitatory amino acid (EAA)
      antagonists on the dorsal root stimulation-evoked, short latency (up to 10 ms)
      spinal root reflex potentials of chloralose-urethane anaesthetized C1 spinal rats
      was studied, in order to gain information on the involvement of non-NMDA
      (AMPA/kainate; AMPA = alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionate) and
      NMDA (N-methyl-D-aspartate) receptors in their mediation. The competitive non
      NMDA antagonist, 2,3-dihydroxy-6-nitro-7-sulphamoyl-benzo(F)quinoxaline (NBQX; 1
      32 mg kg-1), the non-competitive non-NMDA antagonist, 1-(amino)phenyl-4-methyl
      7,8-methylendioxy-5H-2,3-benzodiazepine (GYKI 52466; 0.5-8 mg kg-1), the
      competitive NMDA antagonist 3-((+/-)-2-carboxypiperazin-4-yl)-propyl-l-phosphonic
      acid (CPP, 2-8 mg kg-1) and two non-competitive NMDA antagonists: MK-801 (0.5-2
      mg kg-1) and ketamine (2-32 mg kg-1) were used as pharmacological tools. 2.
      Validating the applied pharmacological tools regarding selectivity at the applied
      doses, their effects were tested on direct (electrical) as well as on synaptic
      excitability of motoneurones evoked by intraspinal stimulation. Furthermore,
      their effect was investigated on the responses elicited by microiontophoretic
      application of EAA agonists (AMPA, kainate and NMDA) into the motoneurone pool,
      where the extracellular field potential evoked by antidromic stimulation of the
      ventral root was recorded to detect the effects of EAA agonists. 3. NBQX and GYKI
      52466 were able to abolish completely the mono-, di- and polysynaptic ventral
      root reflexes (MSR, DSR, PSR) and the synaptic excitability of motoneurones,
      while hardly influencing direct excitability of motoneurones. They markedly
      attenuated AMPA and kainate responses whilst having little or no effect on NMDA
      responses. 4. Apparently 'supramaximal' doses of CPP and MK-801 slightly
      inhibited MSR (by about 10%) moderately reduced DSR and PSR (by about 20-30%) and
      did not influence excitability of motoneurones. They selectively blocked
      responses to NMDA. 5. Ketamine dose-dependently inhibited MSR, DSR and PSR.
      Nevertheless, diminution of none of the responses exceeded 50%. It reduced both
      direct and synaptic excitability of motoneurones, thus displaying a local
      anaesthetic-like effect, which may contribute to its reflex inhibitory action. It
      depressed responses to NMDA whilst having negligible effects on responses to AMPA
      and kainate. 6. We conclude that non-NMDA receptors play a substantial role in
      the mediation of MSR, DSR and PSR, while NMDA receptors contribute little to
      this. Neither MSR nor PSR is mediated exclusively by non-NMDA or NMDA receptors,
      respectively. 7. The drugs investigated in this study, with the exception of
      ketamine, proved to be useful tools for elucidation of the involvement of EAA
      receptors in various processes in vivo Keywords: Glutamate receptors; AMPA;
      kainate; NMDA; NBQX; GYKI 52466; CPP; MK-801; spinal reflex; spinal cord

PMID- 7620710
TI  - Acute withdrawal after bremazocine and the interaction between mu- and kappa
      opioid receptors in isolated gut tissues.
AB  - 1. This study was undertaken to investigate whether, after a brief exposure of
      guinea-pig isolated ileum and rabbit jejunum to bremazocine, a kappa-opioid
      agonist also possessing antagonist activity at mu-opioid receptors, the addition
      of opioid antagonists produced withdrawal contractures. Our aim was to verify in
      these tissues the existence of an interaction between the mu- and kappa-opioid
      systems. 2. In guinea-pig ileum preparations previously exposed for 5 min to
      bremazocine at 5.7 x 10(-7) M and 5.7 x 10(-8) M, naloxone (5 x 10(-7) M)
      elicited no response whereas in tissues exposed to a lower bremazocine
      concentration (5.7 x 10(-9) M), naloxone (5 x 10(-7) M) and the selective kappa
      opioid antagonist, nor-binaltorphimine (3.4 x 10(-8) M) both produced a strong
      contracture. 3. Bremazocine (5.7 x 10(-7) M) administered to guinea-pig isolated
      ileum, previously exposed for 5 min to morphine (10(-7) M), induced a withdrawal
      contracture. In contrast, lower bremazocine concentrations (1.4 and 7.1 x 10(-8)
      M) did not elicit a withdrawal contracture. 4. Naloxone (5 x 10(-7) M), added to
      the bath after a 5 min exposure of guinea-pig ileum to morphine (10(-7) M),
      elicited the characteristic withdrawal contracture. Bremazocine (1.4-7.1 x 10(-8)
      M) added 1 min before naloxone (5 x 10(-7) M) inhibited the naloxone withdrawal
      contracture in a dose-related way whereas naloxone 5 x 10(-8) M added 1 min
      before naloxone 5 x 10(-7) M, did not affect the withdrawal response. 5. In the
      rabbit jejunum, bremazocine (1.4-7.1 x 10-8 M) caused a decrease in amplitude in
      the spontaneous tissue activity. In tissues exposed to these bremazocine
      concentrations, naloxone(5 x 10-7 M) elicited a marked contracture. A similar
      contracture occurred when nor-binaltorphimine(3.4 x 10-8 M) was added in place of
      naloxone. These effects were dose-related to the bremazocine concentration. The
      specific K-agonist, U-50,488H (5 x 10-8 M), elicited the same effects as
      bremazocine.6. These findings show that stimulation of K-opioid receptors induces
      a state of dependence that is not prevented by blocking the pi-opioid system. The
      observation that low bremazocine concentrations inhibit the morphine-induced
      withdrawal contractures, indicates an interaction between the micro- and K-opioid
      system in guinea-pig isolated ileum, similar to that observed in the whole
      animal.

PMID- 7620712
TI  - A novel enhancing effect of clofilium on transient outward-type cloned cardiac K+
      channel currents.
AB  - 1. The antiarrythmic drug, clofilium, has been shown to block several types of K+
      channel currents. To investigate the effects of clofilium on the transient
      outward K+ current (Ito), a cloned Ito-type cardiac K+ channel (RHK1) was
      expressed in Xenopus oocytes and the drug effects were examined on whole cell
      currents. 2. Extracellular application of clofilium slightly inhibited the
      current at +60 mV from a holding potential of -80 mV. However, it unexpectedly
      enhanced the current from a holding potential of -60 mV in a dose-dependent
      manner (219 +/- 39% of control at 100 microM). 3. This enhancement is probably
      due to an increase in the ratio of channels in the resting state during steady
      depolarization, since clofilium shifted the inactivation curve in the
      depolarizing direction. 4. LY97119, a tertiary ammonium analogue of clofilium,
      did not exhibit this enhancing effect but only inhibited the current. 5.
      Clofilium may be useful for the study of channel inactivation because this type
      of phenomenon has not been reported for any other drug.

PMID- 7620711
TI  - An electrophysiological investigation of the properties of a murine recombinant 5
      HT3 receptor stably expressed in HEK 293 cells.
AB  - 1. The pharmacological and biophysical properties of a recombinant 5-HT3 receptor
      have been studied by use of patch-clamp techniques applied to HEK 293 cells
      stably transfected with the murine 5-HT3 R-A cDNA. 2. At a holding potential of 
      60 mV, 77% of cells investigated responded to ionophoretically applied 5-HT with
      an inward current. Such currents were unaffected by methysergide (1 microM), or
      ketanserin (1 microM), but were antagonized in a concentration-dependent and
      reversible manner by the selective 5-HT3 receptor antagonist, ondansetron (IC50 =
      440 pM) and the non-selective antagonists (+)-tubocurarine (IC50 = 1.8 nM) and
      metoclopramide (IC50 50 nM). 3. The 5-HT-induced current reversed in sign (E5-HT)
      at approximately -2mV and exhibited inward rectification. The influence of extra-
      and intracellular ion substitutions upon E5-HT indicates the 5-HT-evoked current
      to be mainly mediated by a mixed monovalent cation conductance. 4. Calcium and
      magnesium (0.1-10 nM) produced a concentration-dependent, voltage-independent,
      inhibition of the 5-HT-induced response. Zinc (0.3-300 microM) exerted a biphasic
      effect with low concentrations enhancing, and high concentrations depressing, the
      5-HT-evoked current. 5. Fluctuation analysis of inward currents evoked by a low
      (1 microM) concentration of 5-HT suggests the current to be mediated by the
      opening of channels with a conductance of 420 fS. 6. The pharmacological and
      biophysical properties of the 5-HT3 R-A are similar to those previously described
      for 5-HT3 receptors native to murine neuroblastoma cell lines, with the exception
      that the function of the recombinant receptor was enhanced by low concentrations
      of zinc. This observation suggests that the properties of the native receptor are
      not completely represented by the 5-HT3 R-A subunit alone.

PMID- 7620713
TI  - Antiproliferative effects of A02011-1, an adenylyl cyclase activator, in cultured
      vascular smooth muscle cells of rat.
AB  - 1. The effects of A02011-1, a pyrazole derivative, on the proliferation of rat
      vascular smooth muscle cells (VSMCs) were examined. 2. A02011-1 (1-100 microM)
      concentration-dependently inhibited [3H]-thymidine incorporation into DNA in rat
      VSMCs that were synchronized by 48 h serum depletion and then re-stimulated by
      addition of foetal calf serum (FCS, 10%), platelet-derived growth factor (PDGF,
      10 ng ml-1), 5-hydroxytryptamine (10 microM) or ADP (10 microM). The inhibitory
      effect of A02011-1 was fully reversible. However, FCS-induced [3H]-thymidine
      incorporation into rat endothelial cells was unaffected by A02011-1. 3. The
      concentration of A02011-1 necessary for inhibition of the FCS-induced
      proliferation was similar to that necessary for adenosine 3':5'-cyclic
      monophosphate (cyclic AMP) formation. Adenylyl cyclase activity was increased in
      A02011-1-treated VSMCs, whereas cyclic AMP-specific phosphodiesterase activity
      was unchanged. 4. A02011-1 was equipotent with forskolin but was more potent than
      8-bromo-cyclic AMP against FCS (10%)-induced proliferation. 5. The
      antiproliferative action of A02011-1 was mimicked by 8-bromo-cyclic AMP, a
      membrane-permeable cyclic AMP analogue and was antagonized by 2',5'
      dideoxyadenosine, an adenylyl cyclase inhibitor and by Rp-cyclic AMPS, a
      competitive inhibitor of cyclic AMP-dependent protein kinase (PKA) type I and II.
      3-Isobutyl-1-methylxanthine (IBMX) caused significant potentiation of the
      antiproliferative activity of A02011-1. However, Rp-8-bromo-cyclic GMPS and
      staurosporine did not affect the antiproliferative activity of A02011-1. 6.
      A02011-1 still inhibited the FCS-induced DNA synthesis even when added 10-18h
      after restimulation of the serum-starved VSMCs with 10% FCS. Flow cytometry in
      synchronized cells revealed an acute blockade of FCS-inducible cell cycle
      progression at a point in the G,/S phase in A02011-1-treated cells. The
      inhibition of proliferation by A0201 1-1 was shown to be independent of cell
      damage,as documented by several criteria of cell viability.7. These results
      indicate that A0201 1-1 inhibition of VSMC proliferation was mediated by cyclic
      AMP and was due to a delay in the progression from the G1 into S phase of the
      cell cycle. A02011-1 did not cause cell toxicity and may thus hold promising
      potential for the prevention of atherosclerosis or vascular diseases.

PMID- 7620714
TI  - Potentiation by endothelin-1 of 5-hydroxytryptamine responses in aortae from
      streptozotocin-diabetic rats: a role for thromboxane A2.
AB  - 1. We have previously reported maximum responses to 5-hydroxytryptamine (5-HT)
      are diminished in endothelium-intact and -denuded aortae from rats with
      streptozotocin-induced diabetes of 2-weeks duration. 2. In the present study, the
      thromboxane A2/prostaglandin H2 (TP) receptor antagonist GR32191B (1 microM)
      significantly reduced maximum responses to 5-HT in endothelium-intact aortae from
      both control and diabetic rats. In the presence of GR32191B, maximum responses to
      5-HT, in endothelium-intact aortae from diabetic rats, were still significantly
      reduced compared to those obtained in aortae from controls. 3. GR32191B (1
      microM) had no significant effect on maximum responses to 5-HT in endothelium
      denuded aortae from either control or diabetic rats. 4. Interaction between 5-HT
      (0.1 microM-0.1 mM) and threshold concentrations of endothelin-1 (ET-1) or the
      thromboxane (Tx)A2-mimetic, U46619, were examined in endothelium-intact and 
      denuded aortae from control and 2-week streptozotocin-diabetic rats. 5. Maximum
      responses to 5-HT in the presence of a threshold concentration of ET-1 (3 nM), in
      endothelium-intact aortae from diabetic rats, were not significantly different
      from those of control rats. 6. Maximum responses to 5-HT in the combined presence
      of ET-1 (3 nM) and GR32191B (1 microM), in endothelium-intact aortae from
      diabetic rats, were significantly reduced compared to those obtained in aortae
      from controls. 7. Maximum responses to 5-HT in the presence of ET-1 (3 nM) in
      endothelium-denuded aortae from diabetic rats were significantly reduced compared
      to those from controls. 8. Maximum responses to 5-HT in the presence of a
      threshold concentration of U46619 (20 or 30 nM),in endothelium-intact aortae from
      diabetic rats, were not significantly different from responses of controls.9.
      Maximum responses to 5-HT in the presence of a threshold (5-20 nM) concentration
      of U46619, in endothelium-denuded aortae from diabetic rats, were not
      significantly different from responses of controls.10 The results of the present
      study indicate that endothelial-derived TxA2 contributes to the contractile
      response to 5-HT in aortae from control and diabetic rats. Endothelial-derived
      TxA2 also appears to play a role in the potentiation of 5-HT responses by ET-1 in
      aortae from diabetic rats.

PMID- 7620715
TI  - Human muscarinic receptors expressed in A9L and CHO cells: activation by full and
      partial agonists.
AB  - 1. A comparative study of receptor activation by ten full and partial muscarinic
      agonists was undertaken on the five subtypes of human muscarinic receptors
      expressed at similar receptor densities in Chinese hamster ovary (CHO-K1) cells.
      In addition, m1, m2 and m3 receptors were expressed in mouse fibroblast A9L cells
      in order to compare the influences of cell type on agonist activation of these
      receptors. 2. Receptor-effector coupling efficiencies were greater in CHO than
      A9L cells and agonists displayed greater potencies and similar or greater
      intrinsic activities at CHOm1 and CHOm3 than A9Lm1 and A9Lm3 receptors. Although
      m2 receptor density was 6 fold higher in A9L than CHO cells, carbachol elicited
      significantly greater inhibition of adenosine 3':5'-cyclic monophosphate (cyclic
      AMP) formation in CHOm2 cells. These data suggest that not only receptor density
      but receptor-effector coupling and/or coupling efficiencies play significant
      roles in agonist-induced responses. 3. In CHO cells, receptor-effector coupling
      efficiencies were m3 = m1 > m5. Although CHOm5 receptors were the least
      efficiently coupled, some partial agonists displayed higher intrinsic efficacies
      at m5 than m3 receptors suggesting that, in CHO cells, m5 and m3 receptors may
      activate different G proteins and/or effectors to stimulate inositol
      monophosphate (IP1) formation. 4. McN-A-343 was a functionally selective m4
      agonist. It had little or no agonist activity at m3 receptors expressed in either
      A9L or CHO cells. The slopes of McN-A-343 concentration-response curves inCHOm2
      cells were significantly lower than the slopes obtained with this compound in
      CHOm4 cells suggesting that the mode of activation by McN-A-343 differed between
      the two muscarinic receptors negatively coupled to adenylyl cyclase.5. Cloned
      receptors provide valuable tools for the study of agonist-receptor interaction
      and agonist receptor activation but caution should be applied in assuming that
      the results are valid for all cell types or for tissue-expressed receptors.

PMID- 7620716
TI  - Comparative study of endotoxin-induced hypotension in kininogen-deficient rats
      with that in normal rats.
AB  - 1. The aim of this study was to clarify the role of endogenous bradykinin (BK) in
      the hypotensive response induced by lipopolysaccharide (LPS) by comparing the
      degree of hypotension caused by LPS in a strain of specific pathogen-free (SPF)
      Brown Norway (B/N), kininogen-deficient mutant Katholiek rats with that of B/N
      normal Kitasato rats. 2. The dose-dependent hypotensive responses caused by
      intravenous injection of BK (1-100 nmol kg-1) or platelet-activating factor (PAF,
      0.003-1 microgram kg-1), were not different in the two strains of rats used.
      However, there was a strong difference in the hypotensive response induced by LPS
      in kininogen-deficient and normal rats; in normal rats the hypotensive response
      was composed of two phases (15 min and 70-80 min after LPS injection), but in
      kininogen-deficient rats LPS caused a delayed (second phase), but not an acute
      (first phase) hypotension. 3. We demonstrate that Hoe 140 (1 mg kg-1, i.v.) is a
      potent, selective, and long-lasting antagonist of the hypotensive effects of BK.
      Hoe 140 diminished the hypotension caused by LPS in normal rats to the level
      observed in kininogen-deficient rats, but had no effect on the hypotension caused
      by LPS in kininogen-deficient rats. 4. TCV309 (0.1 mg kg-1, i.v.) selectively
      inhibited the hypotension caused by repetitive injection of PAF for up to 180
      min. Pretreatment with TCV309 caused a near complete inhibition of the LPS
      induced hypotension in kininogen-deficient and normal B/N rats. 5. In the normal
      rats, dexamethasone (0.5 mg kg-1, i.p.) inhibited the second phase of the
      hypotension induced by LPS, but not the first phase of the hypotension. 6. A
      small amount of BK (0.1 nmol kg-1) potentiated the hypotensive action of PAF
      (0.01 microg kg-1),when they were injected simultaneously.7. In conclusion, we
      demonstrate that formation of endogenous BK contributes primarily to the
      acute,but not to the delayed hypotension afforded by endotoxin in the rat. In
      contrast, formation of endogenous PAF contributes to both the acute and the
      delayed hypotension afforded by endotoxin in vivo.

PMID- 7620717
TI  - Release by ultraviolet B (u.v.B) radiation of nitric oxide (NO) from human
      keratinocytes: a potential role for nitric oxide in erythema production.
AB  - 1. The mechanism of human sunburn is poorly understood but its characteristic
      features include the development of erythema. In this study we attempted to
      determine whether human keratinocytes possess a nitric oxide (NO) synthase (NOS),
      if this enzyme could be activated to release NO following exposure to ultraviolet
      B (u.v.B) and to define whether this photo-induced response could be involved in
      the pathogenesis of sunburn erythema. 2. Treatment of human keratinocytes with
      various doses of u.v.B (290-320 nm) radiation (up to 100 mJ cm-2) resulted in a
      dose-dependent release of NO and cyclic GMP production that was reduced by NG
      monomethyl-L-arginine (L-NMMA). 3. u.v.B irradiation of keratinocyte cytosol at
      varying doses (up to 50 mJ cm-2), resulted in a gradual rise in NO production,
      with a concomitant increase in soluble guanylate cyclase activity (sGC). 4. NOS
      isolated from the keratinocyte cytosol was constitutively expressed and was
      dependent on NADPH, Ca2+/calmodulin, tetrahydrobiopterin and flavins. 5. In
      reconstitution experiments, when purified NOS was added to purified sGC, both
      isolated from keratinocyte cytosol, a four fold increase in cyclic GMP was
      observed. The GMP was increased by NO synthesized following u.v.B radiation (up
      to 20 mJ cm-2) of NOS. 6. In in vivo experiments, guinea-pigs were subjected to
      u.v.B light. A Protection Factor (PF) of 8.71 +/- 2.85 was calculated when an
      emulsified cream formulation containing L-NMMA (2%) was applied to their skin. 7.
      The present results indicate that u.v.B radiation acts as a potent stimulator of
      NOS in keratinocytes. NO is lipophilic and may diffuse out of the keratinocytes,
      activating sGC in endothelial cells and neighbouring smooth muscle cells. This
      may be a major part of the integrated response of the skin leading to
      vasodilatation and erythema.

PMID- 7620718
TI  - Effects of tyrosine kinase inhibitors on the contractility of rat mesenteric
      resistance arteries.
AB  - 1. A pharmacological characterization of tyrosine kinase inhibitors (TKI)
      belonging to two distinct groups (competitors at the ATP-binding site and the
      substrate-binding site, respectively) was performed, based on their effects on
      the contractility of rat mesenteric arteries. 2. Both the ATP-site competitors
      (genistein and its inactive analogue, daidzein) and the substrate-site
      competitors (tyrphostins A-23, A-47 and the inactive analogue, A-1) reversibly
      inhibited noradrenaline (NA, (10 microM)) and KCl (125 mM) induced contractions,
      concentration-dependently. Genistein was slightly but significantly more potent
      than daidzein; the tyrphostins were all less potent than genistein, and there
      were no significant differences between the individual potencies. The tyrosine
      kinase substrate-site inhibitor bis-tyrphostin had no inhibitory effect. 3.
      Genistein, daidzein, A-23 and A-47 each suppressed the contraction induced by
      Ca2+ (1 microM) in alpha-toxin permeabilized arteries. A-1 and bis-tyrphostin had
      little or no effect on contraction of the permeabilized arteries. 4. Genistein
      was significantly more potent than daidzein with respect to inhibition of the
      contraction induced by 200 nM Ca2+ in the presence of NA (100 microM) and GTP (3
      microM). The effect of A-23, A-47, A-1 and bis-tyrphostin was similar in
      permeabilized arteries activated with Ca2+ (200 nM) + NA (100 microM) + GTP (3
      microM) and permeabilized arteries activated with 1 microM Ca2+. 5. Genistein (30
      microM) reduced the fura-2 measured intracellular calcium activity ([Ca2+]j) in
      arteries stimulated with NA but had no effect on [Ca2+]i in arteries stimulated
      with KCl (125 mM).6. The potent effect of the TKIs in this study is consistent
      with a role for tyrosine kinases in the mechanisms which regulate both
      cytoplasmic Ca2+ levels and the effect of Ca2+ on the contractile apparatus in
      smooth muscle cells in resistance arteries. However, the results must be
      interpreted cautiously because the enzyme inhibitors may have a poor specificity
      in intact tissues and because the presumed inactive analogues had potent effects.

PMID- 7620720
TI  - Effects of semotiadil fumarate, a novel Ca2+ antagonist, on cytosolic Ca2+ level
      and force of contraction in porcine coronary arteries.
AB  - 1. The mechanisms of action of semotiadil fumarate, a novel Ca2+ antagonist, were
      examined by measuring the cytosolic Ca2+ level ([Ca2+]i) and force of contraction
      in porcine coronary arteries, and by determining [3H]-pyrilamine binding to
      bovine cerebellar membranes. 2. Semotiadil or verapamil (0.1 and 1 microM)
      inhibited both the high KCl-induced increases in [Ca2+]i and force in a
      concentration-dependent manner. 3. Histamine (30 microM) produced transient
      increases followed by sustained increases in [Ca2+]i and force, which were
      inhibited by semotiadil and verapamil (1 and 10 microM). The agents were
      different in that semotiadil reduced the maximum [Ca2+]i and force responses to
      histamine, but not pD2 values, whereas verapamil did reduce the pD2 values for
      histamine, but not the maximum responses. 4. Verapamil (10 microM), but not
      semotiadil, inhibited histamine-induced increases in [Ca2+]i and force in Ca(2+)
      free solution. Neither semotiadil nor verapamil affected the increases in [Ca2+]i
      and force induced by caffeine. Semotiadil even at the higher concentration (10
      microM) did not displace specific binding of [3H]-pyrilamine to bovine cerebellar
      membranes. 5. These results suggest that semotiadil inhibits both KCl- and
      histamine-induced contractions mainly by blocking voltage-dependent L-type Ca2+
      channels.

PMID- 7620719
TI  - Enhancement of cyclic AMP accumulation mediated by 5-HT after chronic
      amitriptyline treatment in NG 108-15 cells.
AB  - 1. The effects of chronic in vitro administration of amitriptyline, a tricyclic
      antidepressant, on 5-hydroxytryptamine (5-HT) receptor-mediated adenylyl cyclase
      activity was studied in the neuroblastoma x glioma hybrid cell line, NG 108-15.
      2. Treatment of NG 108-15 cells with 8 microM amitriptyline for 3 days increased
      forskolin-stimulated (0.1 microM) adenosine 3':5'-cyclic monophosphate (cyclic
      AMP) accumulation. Addition of 5-HT (0.1-100 microM) increased forskolin
      stimulated cyclic AMP accumulation in amitriptyline-treated cells in a
      concentration-dependent manner. However, 5-HT did not affect forskolin-stimulated
      cyclic AMP accumulation in untreated cells. 3. The 5-HT4 receptor agonist, 5
      methoxytryptamine, significantly enhanced forskolin-stimulated cyclic AMP
      accumulation in amitriptyline-treated cells. In contrast, amitriptyline treatment
      failed to modify 8-hydroxy-2-(di-n-propylamine) tetralin-induced inhibition of
      forskolin-stimulated cyclic AMP accumulation. 4. Pretreatment of cells with
      pertussis toxin did not affect the 5-HT-induced enhancement of cyclic AMP
      accumulation. 5. The 5-HT-induced enhancement of cyclic AMP accumulation in
      amitriptyline-treated cells was attenuated by the 5-HT4 receptor antagonists, GR
      113808 and ICS 205-930, with relatively low potency. However, spiperone, SCH
      23390, and pindolol were completely ineffective against this 5-HT-induced
      enhancement. 6. Chronic treatment with amitriptyline did not modify the cyclic
      AMP production stimulated by prostaglandin E1 or cholera toxin. This treatment
      also had no effect on GTP gamma S-, NaF-, and Mn(2+)-stimulated cyclic AMP
      accumulation in isolated cell membranes. 7. Chronic treatment with the 5-HT
      receptor antagonists, pindolol or ICS 205-930, did not inhibit the 5-HT-induced
      enhancement of cyclic AMP accumulation.8. Chronic treatment with other
      antidepressant drugs, imipramine, mianserin or paroxetine, elicited the 5-HT
      induced enhancement of cyclic AMP accumulation.9. Taken together, these results
      suggest that chronic amitriptyline treatment of NG 108-15 cells causes 5-HT to
      enhance forskolin-stimulated cyclic AMP accumulation by enhancing 5-HT receptor
      mediated stimulation of adenylyl cyclase and not by reducing 5-HT-mediated
      inhibition of adenylyl cyclase. The 5-HT-induced enhancement of cyclic AMP
      accumulation in amitriptyline-treated cells may result from changes at the level
      of the 5-HT receptor rather than at the level of G, proteins or adenylyl cyclase.
      It is unlikely that this enhancement of cyclic AMP accumulation is caused by long
      term antagonism of the 5-HT receptor by amitriptyline.

PMID- 7620723
TI  - Perspectives on training in gastroenterology.
AB  - Training in endoscopy has changed dramatically during the past 20 years and will
      probably change even more over the next 10 years. To confront these changes more
      effectively, the leaders of the four major digestive disease societies,
      collectively known as the Gastroenterology Leadership Council (GLC), encouraged
      the formation of a training director's committee. This article discusses several
      of the issues that the GLC Training Directors Committee has dealt with.

PMID- 7620721
TI  - Subgroups among mu-opioid receptor agonists distinguished by ATP-sensitive K+
      channel-acting drugs.
AB  - 1. We evaluated the effects of the i.c.v. administration of different K+ channel
      blockers (gliquidone, 4-aminopyridine and tetraethylammonium) and an opener of K+
      channels (cromakalim) on the antinociception induced by several mu-opioid
      receptor agonists in a tail flick test in mice. 2. The s.c. administration of all
      agonists of mu-opioid receptors tested (morphine, 1-16 mg kg-1; metadone, 1-6 mg
      kg-1; buprenorphine, 0.04-0.64 mg kg-1; fentanyl, 0.02-0.32 mg kg-1 and
      levorphanol, 0.2-3.2 mg kg-1) elicited a dose-dependent antinociceptive effect.
      3. The ATP-sensitive K+ channel blocker, gliquidone (0.06-16 micrograms per
      mouse, i.c.v.) antagonized the antinociception induced by buprenorphine, morphine
      and metadone. In contrast, gliquidone (0.25-160 micrograms per mouse) did not
      modify the antinociceptive effects of fentanyl and levorphanol. 4. Cromakalim (4
      64 micrograms per mouse, i.c.v.), an opener of ATP-sensitive K+ channels,
      enhanced the antinociception produced by buprenorphine, morphine, and methadone,
      and did not significantly modify the antinociceptive effects of fentanyl and
      levorphanol. 5. The i.c.v. administration of the K+ channel blockers
      tetraethylammonium (10 micrograms per mouse) or 4-aminopyridine (25 ng per mouse)
      did not significantly modify the antinociception induced by any mu-opioid
      receptor agonist tested. 6. These results suggest that the opening of ATP
      sensitive K+ channels is involved in the antinociceptive effect of morphine,
      buprenorphine and methadone, but not in that of fentanyl or levorphanol.
      Consequently, we suggest that at least two subgroups can be distinguished among
      mu-opioid receptor agonists, each inducing antinociception through different
      effector mechanisms.

PMID- 7620722
TI  - The effect of nitric oxide donors on haemodynamics and blood flow distribution in
      the porcine carotid circulation.
AB  - 1. The role of nitric (NO) in the regulation of capillary and arteriovenous
      anastomotic blood flow was evaluated in the carotid circulation of the pig. For
      this purpose, the effect of intracarotid (i.c.) infusions of saline and two NO
      donors, nitroprusside sodium (NPR) and S-nitroso-N-acetylpenicillamine (SNAP) in
      concentrations of 3-100 micrograms min-1 was studied on systemic haemodynamics
      and carotid blood flow and its distribution in anaesthetized pigs with low
      arteriovenous anastomotic blood flow, by use of the radioactive microsphere
      method. 2. Apart from heart rate, which increased after both NPR and SNAP, no
      major changes in systemic haemodynamic variables were observed. In contrast to
      saline, both NPR and SNAP increased common carotid blood flow, vascular
      conductance and vascular pulsations dose-dependently. 3. The distribution of the
      carotid artery blood flow over capillary and arteriovenous anastomotic fraction
      remained stable after saline infusions. Both NPR and SNAP enhanced total
      capillary blood flow and conductance. In contrast to NPR, arteriovenous
      anastomotic blood flow and conductance were increased by SNAP. 4. At the tissue
      level, capillary blood flow increases following NPR or SNAP were reflected by an
      increase in both extracerebral and dural blood flow without changes in total
      brain blood flow. 5. These results indicate that both NO donors cause arteriolar
      dilatation together with enhanced vascular pulsations in the carotid circulation
      of the pig. Probably by way of a 'steal' phenomenon, this pronounced arteriolar
      dilatation limits the effect of NO donors on arteriovenous anastomoses. 6. The
      results of the present investigation support the contention that dilatation of
      intra- and extra cranial arteries and arteriovenous anastomoses leads to
      increased vascular pulsations, which (rather than increased blood flow) could, at
      least in part, be responsible for the headache caused by nitro vasodilators.

PMID- 7620724
TI  - Endoscopy training in a three-year curriculum.
AB  - Endoscopic training has become an increasingly important part of training in
      gastroenterology in recent years. As plans are developed to require 3 years of
      training in gastroenterology for board eligibility, the outline of a 3-year
      curriculum is proposed that would incorporate both "basic" training and
      "advanced" training (where offered) in endoscopy as integral components of a
      flexible plan designed to suit the needs and capabilities of both trainees and
      programs.

PMID- 7620725
TI  - The art of endoscopic instruction.
AB  - This article discusses the effect that new and changing circumstances of health
      care will have on training in endoscopic procedures and describes basic elements
      and principles of training that can make training programs equal to the task.

PMID- 7620727
TI  - Novel methods for endoscopic training.
AB  - The development of past, present, and future endoscopic training methods is
      described. A historical perspective of endoscopy training guidelines and devices
      is used to demonstrate support for the use of novel endoscopic training
      techniques. Computer simulation of endoscopy, interactive learning, and virtual
      reality applications in endoscopy and surgery are reviewed. The goals of
      endoscopic simulation and challenges facing investigators in this field are
      discussed, with an emphasis on current and future research.

PMID- 7620726
TI  - Advanced training in endoscopy.
AB  - Endoscopy has revolutionized all aspects of digestive diseases and has increased
      the popularity of gastroenterology and minimally invasive surgery. These changes
      as well as improved technology and innovative applications of standard procedures
      call for more sophisticated endoscopic training. This article discusses what that
      training and curriculum should be and how it can be conducted.

PMID- 7620728
TI  - Evaluation of trainee competence.
AB  - The ongoing evaluation of endoscopic competence is an essential element of every
      medical and surgical endoscopic training program. The primary goal of this
      evaluation is to assure the greatest benefit for patients with digestive
      diseases. Observational methods to assess competence plus current guideline
      recommendations for certification and proctoring are discussed in this article.

PMID- 7620729
TI  - Providing feedback.
AB  - Although the importance of providing feedback to our fellows, residents, and
      colleagues is acknowledged, this key step in the acquisition of clinical skills
      is often omitted from training programs. When effective feedback is provided and
      focuses on directly observable skills and behaviors, important personal and
      educational progress can occur. This article presents the key components of
      formative feedback as distinct from performance evaluation; discusses the
      barriers to providing effective feedback; and makes specific suggestions for
      beginning the process of giving useful feedback to trainees.

PMID- 7620730
TI  - The problem fellow.
AB  - Problems encountered in training GI fellows range from illnesses that affect
      patient care (impaired physician) to problems in the timely acquisition of the
      technical, cognitive, and personal skills required to perform endoscopy
      competently and independently. The key for fellowship programs in addressing
      potential problems is to develop a system that monitors fellows and provides
      regular feedback along with early intervention. The existence of such a program
      will benefit the program, the fellows, and the public.

PMID- 7620731
TI  - Retraining in endoscopy.
AB  - This article outlines a program developed by the American Society for
      Gastrointestinal Endoscopy (ASGE) for training gastroenterologists in endoscopy
      techniques that had not been introduced at the time of their fellowships.
      Discussed are prerequisites for students, criteria for teachers, elements for the
      teaching program, and methods for documenting the experience. Problems to be
      anticipated are highlighted and include liability, justification of an attenuated
      training experience, and the acceptability of such a program for purposes of
      obtaining privileges. Also considered is ASGE's experience with this program and
      the potential for its use in other nontraditional teaching situation, for
      example, managed care.

PMID- 7620732
TI  - Malpractice in gastrointestinal endoscopy.
AB  - Malpractice actions arising from gastrointestinal endoscopic care most frequently
      allege improper performance of the procedure and errors in diagnosis. Virtually
      all claims alleging an iatrogenic injury involve perforation, which in principle
      should be defensible if proper informed consent is documented. Allegations of
      errors in diagnosis primarily pertain to missed colon cancer. The relative
      malpractice claim risk of sigmoidoscopy, esophagogastroduodenoscopy, endoscopic
      retrograde cholangiopancreatography, and colonoscopy are similar. This article
      summarizes the basic elements of a malpractice suit, the recent history of
      medical malpractice, and the relationships between iatrogenic patient injury and
      malpractice suits. The allegations in malpractice claims against endoscopists are
      examined.

PMID- 7620733
TI  - Risk management in endoscopic practice.
AB  - As illustrated, the practice of gastrointestinal endoscopy is not without risks.
      All physicians who perform endoscopy should be mindful of the tenets of risk
      management and how they apply to their endoscopic practices. Retrospective review
      of individual endoscopic practice habits should be performed yearly and
      modifications made where necessary. Hospital quality assurance committees should
      have gastrointestinal endoscopist representation. These committees should have as
      a component of their responsibilities a commitment to physician education.

PMID- 7620734
TI  - Medical-legal consultation in gastroenterology.
AB  - Medical-legal consultation is a challenging adjunct to gastroenterology practice,
      encountering a wide range of problems. Cases in this series involved both medical
      malpractice and other liability issues, but only a minority of cases involve
      dendoscopic complications. Consultants can develop skills to efficiently perform
      independent medical examinations, give depositions and testimony in court. The
      expert must be informed, detached, and follow guidelines of ethical behavior in
      providing his or her opinions. The 1993 ruling by the Supreme Court in the
      Daubert case sets new standards for scientific testimony by expert witnesses.

PMID- 7620735
TI  - Current ethical and legal issues in gastrointestinal endoscopy.
AB  - The ethical and legal aspects of gastroenterology practice have changed over the
      past 20 years just as remarkably as the technological features of care. Answers
      to questions like "May competent adult patients refuse medical treatment?" and
      "Is the medically-mediated delivery of nutrition and hydration a 'medical
      treatment'?" must be considered in light of the Cruzan case and new arguments
      about the benefits and burdens of feeding tubes.

PMID- 7620736
TI  - Prevention of hospital liability for granting privileges to unqualified
      physicians.
AB  - The rise in medical malpractice claims has resulted in the widespread development
      of risk management programs. These programs have relevance to the practice of
      gastrointestinal endoscopy with regard to identifying and addressing factors that
      place the gastrointestinal endoscopist and his or her patient at risk for
      procedure-related complications and adverse outcomes. Illustrative clinical
      examples and commentary regarding gastrointestinal endoscopy as it relates to the
      tort of professional liability are provided. Recommendations regarding
      gastrointestinal risk management are formulated.

PMID- 7620737
TI  - Endoscopic training directors: a few legal and ethical considerations.
AB  - This article has set out several relevant legal and ethical considerations for
      gastrointestinal endoscopic trainers. Fundamental liability issues for the
      trainer and trainee were reviewed, including the theories of vicarious liability.
      Endoscopic complications were viewed from a legal vantage point. Then,
      complications were analyzed from the perspective of how to teach the trainee to
      best risk-manage these problems. The concept of the standard of care was
      presented and was emphasized as a key teaching point. Adequate and accurate
      record keeping is underscored for its many useful purposes, including
      substantiating privilege requests and the termination of inadequate trainees.
      Lastly, the letter of recommendation was reviewed and the potential of liability
      associated with inaccurate letters was delineated.

PMID- 7620738
TI  - Informed consent for endoscopy.
AB  - The process of informed consent is an ethical and legal mandate. The medical
      informed consent doctrine enables adult patients to make their own treatment
      decisions based on adequate disclosure of information by the endoscopist. The
      physician must disclose to the patient the nature, benefits, risks, and
      alternatives of the procedure being performed. It is incumbent upon the
      endoscopist to know the standard of disclosure in his or her jurisdiction. The
      process of informed consent will strengthen the physician-patient relationship
      and can be used as a valuable risk management tool.

PMID- 7620739
TI  - Case reports and confidentiality. Opinion is sought, medical and legal.

PMID- 7620740
TI  - Patient satisfaction in mental health care. Evaluating an evaluative method.

PMID- 7620741
TI  - Schizophrenia--a brain disease? A critical review of structural and functional
      cerebral abnormality in the disorder.
AB  - BACKGROUND: With genetic and neurochemical findings pointing to a biological
      aetiology, considerable effort has been devoted to finding direct evidence of
      brain abnormality in schizophrenia. METHOD: CT, MRI, post-mortem and functional
      imaging studies are reviewed to assess which structural and/or functional brain
      abnormalities have been consistently demonstrated. RESULTS: The only well
      established structural abnormality in schizophrenia is lateral ventricular
      enlargement; this is modest and there is a large overlap with the normal
      population. There is no consensus on the presence of any localised structural
      abnormality from MRI and post-mortem studies, but the most promising findings
      concern temporal lobe limbic structures. Hypofrontality is not a well-replicated
      finding in schizophrenia under resting conditions, but the evidence is stronger
      for a selective association with negative symptoms. A number of studies have
      found hypofrontality under conditions of neuropsychological task activation.
      However, findings in these studies are divided and a recent methodologically
      sophisticated study has failed to confirm it, although this study suggested a
      decoupling of prefrontal and temporal function. CONCLUSION: Schizophrenia is
      characterised by minor structural abnormality which, in the case of lateral
      ventricular enlargement, may be better understood as a risk factor than a
      causative lesion. The functional imaging findings are not transparent but suggest
      that, as a disorder, schizophrenia shows complex alterations in regional patterns
      of activity rather than any simple deficit in prefrontal function.

PMID- 7620742
TI  - In the shadow of adversity: the evolution and resolution of anxiety and
      depressive disorder.
AB  - BACKGROUND: It was proposed to explore the longitudinal relationship between
      adverse experience and mental health; in particular, whether particular adverse
      experiences influence the form of subsequent expression of morbidity. METHOD:
      Three groups of women were selected: 64 whose marital partner had recently died,
      143 whose husbands had recently experienced a myocardial infarction and a third
      group of 32 women who had sought protection in a Women's Aid refuge. An initial
      interview assessed psychiatric status according to the RDC for the six months
      before the event and up to the time of interview, and a second interview was
      completed four months after the event had occurred. The course was assessed using
      the Longitudinal Interval Follow-up Evaluation. RESULTS: For the coronary group,
      the prevalence of psychiatric disorder doubled following the experience of the
      event, and was most pronounced for anxiety disorder. For the bereaved, rates
      increased over eight times for major depressive disorder and more than twice for
      anxiety disorder, following the loss; for the refuge group, prevalence rates were
      lower after entering the refuge than those before. Analyses that took account of
      the timing of the onset of disorders showed that in almost half of those
      experienced by the coronary group, and about 40% of the bereaved group, onset pre
      dated the timing of the event. CONCLUSIONS: The results further advance knowledge
      of the evolution and form of psychiatric conditions following the experience of
      severe adversity.

PMID- 7620743
TI  - Childbirth: life event or start of a long-term difficulty? Further data from the
      Stoke-on-Trent controlled study of postnatal depression.
AB  - BACKGROUND: This paper reports further data from the Stoke study of postnatal
      depression and examines whether psychosocial characteristics and symptom profiles
      differ between postnatal and control depression. METHOD: Two hundred and thirty
      two postnatal and non-postnatal control women were screened with the Edinburgh
      Postnatal Depression Scale; all high scorers and a sample of low scores were
      interviewed with the Standardised Psychiatric Interview and modified Social
      Maladjustment Schedule. Depression was diagnosed using the Research Diagnostic
      Criteria. RESULTS: Postnatal but not control depression was associated with a
      poor relationship with the woman's own mother and greater occupational
      instability. Depression in control women was associated with low income, having
      three or more children, performing manual work and occupational dissatisfaction,
      but postnatal depression was not. There were no differences in the symptom
      profiles of the postnatal and control women nor between early and late onset
      postnatal depression. CONCLUSION: Depression is a common and socially disabling
      disorder affecting mothers of young children. Postnatal depression is more
      contingent on acute biopsychosocial stresses caused by the arrival of a new
      family member. Depression in women with older children is more closely related to
      longer term social adversity.

PMID- 7620744
TI  - Increased risk of affective disorders in males after second trimester prenatal
      exposure to the Dutch hunger winter of 1944-45.
AB  - BACKGROUND: Prenatal and perinatal factors have been linked to affective
      disorders. We therefore undertook an exploratory study to determine whether
      prenatal exposure to severe famine was associated with an increased risk of
      affective disorders. METHOD: Monthly birth cohorts that were exposed and
      unexposed to the Dutch Hunger Winter of 1944-45 were identified. The cumulative
      incidences of affective psychoses and neurotic depression (ICD-9 criteria) were
      compared between exposed and unexposed cohorts during each trimester of
      gestation. RESULTS: The relative risk (RR) of affective psychosis (broad and
      restricted definitions) among persons exposed to famine during the second
      trimester was significantly increased (broad: RR (95% confidence interval) = 1.62
      (1.19, 2.20); restricted: 1.59 (1.14, 2.21)). Separate analysis by gender showed
      a significant association among males (broad: 2.26 (1.43, 3.57); restricted: 2.40
      (1.49, 3.89), but not females (broad: 1.28 (0.84, 1.94); restricted: 1.17 (0.73,
      1.76)). The risk of neurotic depression was not increased after prenatal famine
      exposure. CONCLUSIONS: These results suggest a possible relationship between
      prenatal famine during the second trimester and affective psychosis, lending
      plausibility to reports that have associated affective psychoses with prenatal
      exposures. Further studies of this relationship are warranted.

PMID- 7620745
TI  - Light therapy for seasonal affective disorder. The effects of timing.
AB  - BACKGROUND: Sixty-eight patients with seasonal affective disorder participated in
      a 10,000-lux light treatment study in which two questions were addressed: do
      response rates differ when the light is applied at different times of the day and
      does short-term rank ordering of morning and evening light influence response
      rates? METHOD: Three groups of patients received a 4-day light treatment: (I) in
      the morning (8.00-8.30 a.m., n = 14), (II) in the afternoon (1.00-1.30 p.m., n =
      15) or (III) in the evening (8.00-8.30 p.m., n = 12). Two additional groups of
      patients received two days of morning light treatment followed by two days of
      evening light (IV, n = 13) or vice versa (V, n = 14). RESULTS: Response rates for
      groups I, II and III were 69, 57 and 80% respectively, with no significant
      differences between them. Response rates for groups IV and V were 67 and 50%
      respectively; this difference was not significant and these percentages did not
      differ significantly from those of groups I and III. CONCLUSIONS: The results
      indicate that the timing of light treatment is not critical and that short-term
      rank ordering of morning and evening light does not influence therapeutic
      outcome.

PMID- 7620746
TI  - Life events and senile dementia. Affective symptoms.
AB  - BACKGROUND: Previous research in the elderly has linked threatening life events
      with depression. Dementia sufferers are known to be sensitive to stressful
      changes in their daily life such as relocation. This study investigates whether
      threatening life events are associated with depressive symptoms in dementia
      sufferers. METHOD: Using the Life Events and Difficulties Schedule, this study
      examined life events before admission in a group of 70 dementia patients compared
      with two control groups: dementia sufferers in the community and mentally fit
      elderly people matched for age and sex. RESULTS: Life events with severe threat
      were not significantly more frequent in the dementia patients than in two control
      groups. However, depressive symptoms in the dementia sufferers were significantly
      associated with independent severe life events. This strong association was
      maintained when a multivariate analysis was used to control for the effects of
      other social factors and severity of cognitive impairment. This association
      appears to be specific to the threat aspect of life events since there was no
      association between depressive symptoms and events relating to change in the
      social environment. CONCLUSION: In dementia sufferers, threatening life events
      are associated with depressive symptoms. This means that dementia sufferers are
      responsive to stress in the same way as cognitively intact individuals, and
      clinicians need to be more aware of the social influences on them.

PMID- 7620747
TI  - Dementia and cognitive impairment in the oldest old in the community. Prevalence
      and comorbidity.
AB  - BACKGROUND: The study focuses on the prevalence of dementia in the oldest old.
      METHOD: A community sample (n = 402) of the oldest old in Munich (> or = 85
      years) was assessed with different methods. Four instruments and a clinical
      examination were used for case identification: (a) the Geriatric Mental State
      Interview (GMS-A); (b) the Structured Interview for the Diagnosis of Dementia
      (SIDAM); (c) the Global Deterioration Scale (GDS); and (d) the Mini Mental State
      Examination (MMSE). The clinical examination was performed by the interviewing
      physicians, who made their diagnoses according to ICD-10 and DSM-III-R. RESULTS:
      The structured interviews (GMS-A: 25.4%; SIDAM/SISCO: 28.0%; SIDAM/DSM-III-R:
      27.8%; SIDAM/ICD-10: 16.1%) gave lower point prevalence rates of dementia than
      physicians' clinical diagnoses (43.1%). The rates were 21.2% based on the MMSE.
      Depressive syndromes and anxiety syndromes were the most frequent psychiatric
      disturbances associated with dementia in the very old. CONCLUSION: Dementia rates
      were high in the oldest old, showed an increase with age but no sex differences.
      Interview methodology has a major impact on results.

PMID- 7620748
TI  - The longitudinal stability of cognitive impairment in schizophrenia. Mini-mental
      state scores at one- and two-year follow-ups in geriatric in-patients.
AB  - BACKGROUND: Severe cognitive impairment affects many patients with schizophrenia,
      especially geriatric in-patients. Little is known about the course of this
      impairment, however. METHOD: Two hundred and twenty-four geriatric schizophrenic
      in-patients were examined for changes in cognitive functioning over a one-year
      follow-up period, and 45 of them were assessed over a two-year period. In
      addition, the subset of 45 patients participated in a one-week and one-month test
      retest reliability study of the instrument used to assess cognitive impairment,
      the Mini-Mental State Examination (MMSE). RESULTS: The average MMSE scores did
      not change over a one- or two-year follow-up period. The test-retest reliability
      of the scale was extremely good at both retest intervals. CONCLUSION: Among the
      implications of these data are that cognitive changes in geriatric schizophrenic
      patients are very slow and are more consistent with a neurodevelopmental process
      than a neurodegenerative course.

PMID- 7620749
TI  - Positive and negative symptom course in chronic community-based patients. A two
      year prospective study.
AB  - BACKGROUND: The long-term symptom profile of chronic out-patients was studied.
      METHOD: 242 out-patients receiving neuroleptic medications (109 with
      schizophrenia and 133 non-schizophrenics), were studied for positive (SAPS) and
      negative (SANS) symptoms at baseline and at 24 months to investigate whether
      these symptom groups changed over outpatient maintenance treatment. RESULTS:
      Overall and within groups, negative symptoms decreased and positive symptoms
      increased. While the sums of the SANS scores for the schizophrenic patients were
      initially higher, their mean SANS score dropped more over time (P < 0.001), to
      show no difference from non-schizophrenics at follow-up. Positive symptoms
      increased in both groups, although schizophrenics were higher at both times; sub
      scales within the SANS showed different patterns of change. CONCLUSION: Support
      is found for a multidimensional view of both positive and negative symptoms and
      for a reconsideration of the notion of 'progressive downward course' in
      schizophrenia.

PMID- 7620750
TI  - Effect of clozapine on d-fenfluramine-evoked neuroendocrine responses in
      schizophrenia and its relationship to clinical improvement.
AB  - BACKGROUND: Clozapine is an effective antipsychotic that has high affinity for
      serotonin type 2 (5-HT2) receptors. The importance of 5-HT antagonism in the
      overall clinical efficacy of clozapine is unclear. Using a neuroendocrine
      strategy we tested the hypothesis that clinical response to clozapine is related
      to alteration in 5-HT function. METHOD: Ten treatment-resistant schizophrenic
      subjects were treated with clozapine for a mean of 10.3 (s.e. 0.9) weeks; d
      fenfluramine (DFEN) challenge tests were performed before and after treatment
      with concurrent clinical ratings (BPRS, SAPS, SANS) made at the time of testing.
      RESULTS: All patients showed clinical improvement following treatment with
      clozapine. In addition, clozapine produced a significant attenuation of prolactin
      (PRL) and cortisol (CRT) response to DFEN challenge. Change in symptom ratings
      correlated significantly with reduction in PRL response to DFEN challenge.
      CONCLUSIONS: These data show that functional alterations occur in the 5-HT system
      following response to clozapine and lend support to studies suggesting that 5-HT
      is an important component to the spectrum of action of clozapine.

PMID- 7620751
TI  - Expressed emotion. Trait or state?
AB  - BACKGROUND: This exploratory study addresses the question of whether expressed
      emotion (EE) is a response characteristic of the parent (trait) or a parental
      response to specific circumstances or persons (state). METHOD: Seventeen parents
      participated in two audiotaped interviews, using modified versions of the
      Camberwell Family Interview. One interview concerned the child with chronic
      schizophrenia and the other a well sibling. Subsequent ratings of the EE
      variables of critical comments (CC), emotional overinvolvement (EOI) and warmth
      were completed and compared. RESULTS: EE response patterns directed towards
      patients, as compared with towards siblings, were significantly different on two
      measures: EOI (P = 0.01) and warmth (P = 0.02). The parents showed significantly
      more emotional overinvolvement with the child with schizophrenia and
      significantly more warmth towards the well child. CONCLUSIONS: These data suggest
      that the EE variables of EOI and warmth are related to the state of child, and
      the lack of a significant difference in CC suggests that this is a parental
      trait.

PMID- 7620752
TI  - A self-rating scale for measuring neuroleptic side-effects. Validation in a group
      of schizophrenic patients.
AB  - BACKGROUND: A study was conducted to validate a comprehensive self-rating scale
      for measuring side-effects of neuroleptic drugs. METHOD: The Liverpool University
      Neuroleptic Side Effect Rating Scale (LUNSERS), which includes 'red herring'
      items, was twice administered to 50 DSM-III-R schizophrenic patients, who were
      also interviewed using the UKU side-effect rating scale; 50 unmedicated controls
      also completed the LUNSERS: RESULTS: The test-retest reliability of the LUNSERS
      was good (r = 0.811, P < 0.001) as was its concurrent validity against the UKU (r
      = 0.828, P < 0.001). Scores correlated with chlorpromazine equivalent doses (r =
      0.310, P < 0.02). ROC analysis demonstrated that the scale discriminated between
      patients and non-medicated controls, who scored differently for real side-effects
      but not for 'red herring' items. CONCLUSIONS: The LUNSERS is an efficient,
      reliable and valid method of assessing neuroleptic side-effects.

PMID- 7620754
TI  - Long-term fluoxetine treatment of bulimia nervosa. Fluoxetine Bulimia Nervosa
      Research Group.
AB  - BACKGROUND: A large collaborative 8-week study has shown fluoxetine to be
      effective and safe in treating patients with bulimia nervosa. The present study
      evaluated fluoxetine over 16 weeks. METHOD: Fifteen US out-patient psychiatry
      clinics conducted a double-blind parallel study in men and women with DSM-III-R
      bulimia nervosa (483 patients entered, 398 randomised [3:1 ratio, fluoxetine 60
      mg/day or placebo], 225 completed). Outcome measures included change in vomiting
      and binge-eating episodes per week. Eating Disorder Inventory, Clinical Global
      Impressions and Patient's Global Impression. RESULTS: Compared with placebo,
      fluoxetine treatment resulted in significantly greater reductions in vomiting
      (F[1,360] = 14.73, P < 0.0001) and binge-eating (F[1,360] = 14.39, P = 0.0002)
      episodes per week at endpoint and improvement in other outcome measures. Adverse
      event, vital sign and laboratory analyses indicated that fluoxetine was safe.
      CONCLUSION: Fluoxetine appeared to be safe and effective in patients with bulimia
      nervosa for up to 16 weeks.

PMID- 7620753
TI  - A brief mental health outcome scale-reliability and validity of the Global
      Assessment of Functioning (GAF).
AB  - BACKGROUND: The Global Assessment of Functioning (GAF) is a quick and simple
      measure of overall psychological disturbance. However, there is little research
      on the reliability and validity of this measure in severely mentally ill
      populations. METHOD: Multidisciplinary keyworkers assessed 103 patients at
      monthly intervals over a 6-month period. Overall GAF scores were obtained, with
      additional separate ratings for symptoms and disability. These were compared with
      changes in antipsychotic medication and support needs over the same period.
      RESULTS: Satisfactory reliability was obtained for total GAF score and for
      symptom and disability measures, in spite of raters having only one brief
      training session. All GAF scores were associated with current support needs of
      patients. Symptom and disability scores were associated with changes in
      antipsychotic medication in the previous month. Only symptom score was associated
      with increases in antipsychotic medication at time of rating. CONCLUSION: GAF
      proved to be a reliable and, within the limits of the indicators used, a valid
      measure of psychiatric disturbance in our sample of the severely mentally ill.
      Differences in relationships between the three GAF scores and medication/support
      needs indicate the usefulness of obtaining all three scores for monitoring levels
      and type of psychiatric disturbance in this population.

PMID- 7620756
TI  - Psychological debriefing.

PMID- 7620755
TI  - Mental disorders and criminal behaviour.
AB  - BACKGROUND: Using improved methods, findings of higher criminality in a
      psychiatric population were tested. METHOD: An unselected sample of 1265 Swiss in
      patients and a matched control group drawn from the general population were
      studied. Detailed accounts of conviction records served as a measure of criminal
      behaviour. RESULTS: Apart from traffic law violations by men, and violent crimes
      and sexual offences by women, patients were more frequently registered in all
      crime categories. However, there were significant differences between the
      diagnostic groups. Alcoholics and drug users of both sexes had a significantly
      higher criminality rate. A higher rate was also found among female, but not male,
      patients suffering from schizophrenia or related disorders and other, mostly
      organic, disorders. CONCLUSIONS: Alcoholism and drug abuse contribute
      significantly to criminal behaviour, independent of sociodemographic factors;
      however, with a few exceptions, mental disorders such as schizophrenia and
      affective disorders do not contribute to criminal behaviour.

PMID- 7620757
TI  - Charles Bonnet syndrome.

PMID- 7620758
TI  - The nature of dysthymia.

PMID- 7620759
TI  - Where shall we put lithium et al?

PMID- 7620760
TI  - Hypomania induced by gabapentin.

PMID- 7620761
TI  - Schizophreniform psychosis after stage hypnosis.

PMID- 7620762
TI  - Nietzsche, Freud and eternal recurrence of the repressed...

PMID- 7620763
TI  - Post-traumatic stress disorder.

PMID- 7620764
TI  - [The clinical importance of determining fibronectin and the activity of
      proteolysis inhibitors in patients with bronchial asthma complicated by pulmonary
      emphysema].
AB  - Examinations of 27 inpatients with infection-dependent bronchial asthma
      complicated by pulmonary emphysema revealed low levels of fibronectin and alpha
      proteinase inhibitor, which were in a positive correlation. The said deficiency
      was stable in asthmatics and was virtually unchanged as remission was attained.
      Hence, we may propose that the said changes may underlie not only the
      development, but stabilization and progress of pulmonary emphysema in patients
      with the infection-dependent variant of bronchial asthma.

PMID- 7620765
TI  - [The determination of sulfated glycosaminoglycans in urine].

PMID- 7620767
TI  - [The assessment of the immunograms of children with allergic diseases].
AB  - Analysis of immunograms of 189 children with allergic diseases of the reagin type
      (55 with atopic bronchial asthma, 33 with atopic dermatitis, 101 with respiratory
      allergosis) helped single out a complex of immunological parameters which
      markedly and statistically reliably change in this type of allergy in comparison
      with a group of healthy children (n = 25). This complex is recommended to be used
      for the detection of the principal pathogenetic factor of the reagin-type
      allergic diseases and monitoring the therapy efficacy.

PMID- 7620766
TI  - [The determination of C-reactive protein by an immunoenzyme method].
AB  - The developed enzyme immunoassay of C-reactive protein is based on the use of a
      plane modified by a phosphorylcholine derivative lisolecithin. The method is
      highly sensitive (5-8 ng / ml), well reproducible; the correlation coefficients
      in measurements of blood serum C-reactive protein are compatible to results
      obtained by rocket immunoelectrophoresis and capillary precipitation: 0.94-0.98
      and 0.88-0.95, respectively.

PMID- 7620768
TI  - [The serodiagnosis of viral hepatitis C].
AB  - Sensitivities and specificities of four commercial enzyme immunoassay test
      systems manufactured by Ortho (USA), Abbott (USA), Organon (Netherlands),
      Innotest (Belgium) and of three pilot Russian diagnostic agents created at the
      Mazai Research and Production Amalgamation (Moscow) and the D. I. Ivanovskii
      Institute of Virology (Moscow) and Pasteur Institute (St. Petersburg) for
      detection of antibody to hepatitis C have been compared. A high incidence of
      hepatitis C virus infection was revealed in various Moscow populations: blood and
      plasma donors, inpatients, and medical staff.

PMID- 7620769
TI  - [A comparative analysis of the frequency of detecting antibodies to the causative
      agent of tuberculosis with the incidence of discovering relapses in patients with
      respiratory organ tuberculosis].
AB  - A total of 503 patients with tuberculosis in different phases were tested for
      antibodies to M.tuberculosis using a complex of serological tests (indirect
      hemagglutination, passive hemolysis, complement consumption, and enzyme
      immunoassay). The frequency of exacerbations and recurrences and the incidence of
      detection of antibodies to M.tuberculosis were analyzed in patients with abating
      active pulmonary tuberculosis registered in follow-up group II, in patients with
      clinically cured tuberculosis of the respiratory organs (follow-up group III),
      and in convalescents with residual changes after cured tuberculosis but at an
      increased risk of the disease reactivation (follow-up group VII). Tuberculosis
      was found to recur more frequently in the patients producing antibodies to
      M.tuberculosis in comparison with those in whom these antibodies were not
      detected. The author puts forward a hypothesis about a relationship between
      vegetation of M.tuberculosis in residual foci as a latent tuberculous infection
      and production of antibodies to this agent. Despite the relative clinical well
      being and stability of x-ray data, patients with seropositive diagnosis are at a
      high risk of developing relapses of tuberculosis of the respiratory organs, this
      implying that this patient population should be clinically followed up and
      administered courses of antirelapse therapy.

PMID- 7620770
TI  - [A microtitration variant of the latex agglutination reaction in the diagnosis of
      leprosy].
AB  - The authors describe the preparation of antigenic diagnostic agent based on
      stained polyacrolein latex particles conjugated with beta-(3-aminopropyl) 3, 6
      dimethylglucopiranoside (DMG), a synthetic analog of PSL = 1 from M. leprae (L
      PMG), and its use in the microtitration variant of latex agglutination for the
      serological diagnosis of lepra. The test was performed in polystyrene plates. A
      total of 45 blood sera of patients with lepra, 34 sera of subjects who had
      contacts with leper patients, and 148 control samples were tested. The level of
      antibodies to DMG was found to be related to the bacterial loading of the
      patient. If the patients with regressive are seropositive, it means that
      persistent forms of M.leprae are present in their organs and tissues.
      "Nonleprous" sera did not react with L-PMG. The microtitration latex
      agglutination test proved to be highly specific (93.3%) and sufficiently
      sensitive (87.3%). It is rapid and simple, the results may be assessed visually;
      this recommends the method for seroepidemiologic screening in the regions where
      lepra cases are recorded.

PMID- 7620771
TI  - [The determination of antistreptokinase by an immunoenzyme method].
AB  - The sensitivity of enzyme immunoassay (EIA) of antistreptokinase, a new method
      for its measurements, is 10 times higher than the sensitivity of the prototype
      method. EIA is more sensitive than the prototype method, the incorrectness of the
      latter being ruled out; endogenous substrates, patients's blood fibrinogen and
      plasminogen, are used, whose concentrations vary in streptococcal diseases.
      Effects of nonspecific blood proteinase which, together with streptokinase, may
      cause a proteolytic effect, on the results of analysis are also ruled out.
      Microquantities of blood serum are needed for EIA of streptokinase, whereas at
      least 2 ml of plasma is required for the prototype test. The suggested method is
      more informative, since it detects the diagnostic titers in a wider range, vs.
      the prototype technique, and is more diagnostically valuable in comparison with
      other tests for the diagnosis of streptococcal infection, detection of
      antistreptolysin 0 and antihyaluronidase.

PMID- 7620772
TI  - [A method for diagnosing allergy by studying eosinophil morphology].
AB  - A total of 107 children with various clinical manifestations of food allergy were
      examined to investigate the morphological changes of eosinophils under the effect
      of food allergens. Eosinophil "injury" caused by cow milk allergen was detected
      in 71.4%, that caused by hen egg white in 82.4%, and that under the effect of
      fish in 77.8% of the examinees, these data being useful as a laboratory test for
      the diagnosis of food sensitization. Correlation between the index of eosinophil
      injury and late reactions to cow milk, as well as increased reactivity to
      nonspecific stimuli were traced.

PMID- 7620773
TI  - [The diagnostic importance of determining blood serum magnesium].

PMID- 7620774
TI  - [The lipids of the erythrocyte stroma and myocardial ischemia in patients with
      iron-deficiency anemia].
AB  - Red cell stromal lipid fractions (total lipids and phospholipids, triglycerides,
      free fatty acids, cholesterol and its esters, lisophospholipids, sphyngomyelins,
      phosphatidylserines, phosphatidylcholines, phosphatidylethanolamines,
      cardiolipins, phosphatide acids) were measured and ECG A leads at rest analyzed
      in 29 patients with iron-deficiency anemia to detect myocardial ischemia.
      Significant changes in red cell stroma lipid composition were revealed,
      particularly marked in women with myocardial ischemia. Measures aimed at
      normalization of red cell stromal lipid composition in patients with iron
      deficiency anemia may be regarded as one of the factors inhibiting the
      development of myocardial ischemia.

PMID- 7620775
TI  - [The morphology of the peripheral blood erythrocytes in patients with tetralogy
      of Fallot before and after its surgical correction].
AB  - Quantitative changes in red cells were studied by dark field scanning electron
      microscopy of native preparations obtained from patients with Fallot's tetralogy
      of varying severity and duration. Mainly echinocytic transformation of red cells
      was revealed that directly depended on the disease duration. Morphologic findings
      have confirmed the efficacy of surgical correction and drug therapy of Fallot's
      tetralogy.

PMID- 7620777
TI  - [The cytological characteristics of the squamous epithelium of the cervix uteri
      in women living under the conditions of an elevated radiation background].
AB  - Cytomorphological signs of epithelial cells were analyzed in scraping off the
      cervix uteri of 607 women living in the zone of increased radiation background.
      The examined group consisted mainly of women aged 30 to 50. In 9.3% (57 cases)
      dysplastic changes in the squamous epithelium were revealed, among which slight
      dysplasia predominated -- basal-cell hyperactivity (40 cases). No cases of
      malignant transformation were detected. The authors noted some signs which
      commonly do not occur in the absence of an increased radiation background and may
      be conditionally regarded as a result of indirect effect of radiation on female
      cells.

PMID- 7620776
TI  - [The phagocytic activity and the alkaline and acid phosphatase indices of the
      neutrophilic leukocytes in patients with stomach cancer treated with 5
      fluorouracil and zymosan].

PMID- 7620778
TI  - [The importance of the cytological method in the endoscopic diagnosis of
      endobronchitis].
AB  - Analysis of cytograms of 60 patients with endoscopically diagnosed endobronchitis
      showed that in local endobronchitis dysplasia of the bronchial epithelium is more
      frequent than in diffuse endobronchitis. Use of the cytological method during
      primary examination of patients helps form the risk groups.

PMID- 7620779
TI  - [Changes in the buccal epithelium in certain diseases in children].
AB  - Buccal epitheliocytes collected from healthy and sick children aged 1 to 5 years
      were examined. The maximal and minimal size of epitheliocytes was measured and
      their mean size estimated, as was the percent share of cell cytolysis. An
      integral index derived on the basis of these measurements reflects the degree of
      change in the quantitative parameters characterizing the buccal epitheliocytes
      and is in positive correlation with deviations of hematological parameters from
      the norm in children with bronchopulmonary and somatic disease.

PMID- 7620780
TI  - [The colicin selection of the S forms of representatives in the
      Enterobacteriaceae family].
AB  - A method based on a lower sensitivity of S forms to colicines, in comparison with
      R forms, was used for the selection of S forms of bacteria from dissociated
      cultures of E. coli O.124:K72, S. sonnei, and S. flexneri. The cultures are
      inoculated in nutrient agar from the external segment of the zone of bacterial
      growth suppression by colicines D, E1, and V+m, where the content of S forms is
      relatively higher at the expense of death of R forms. The content of S forms in
      the resultant cultures of different strains was 1.7 to 31.1 times higher that in
      the initial cultures.

PMID- 7620781
TI  - [The use of a carboxymethylcellulose coating for titrating the foot-and-mouth
      disease virus by the plate-culture method].

PMID- 7620782
TI  - [The design of bacteriological preparations for the diagnosis of legionellosis].
AB  - The technique of making legionellosis diagnostic preparations is described,
      making use of traditional methods and new modified procedures for isolation and
      purification of the components of serological biosystems. Results of using
      bacteriological preparations in studies of legionellosis are presented.

PMID- 7620783
TI  - [A synthetic nutrient medium for isolating Klebsiella pneumoniae].
AB  - Synthetic nitrate saccharose (NS) nutrient media are offered to be used for
      Klebsiella pneumoniae. NS medium of the following composition is suggested for
      studies of substrates moderately contaminated with microorganisms: 20 g agar
      agar, 1 g potassium nitrate, 2 g disubstituted potassium phosphate, monopotassium
      phosphate, 20 g saccharose, and 1 1 distilled water. NSK medium is offered for
      the isolation of Klebsiella from material abundantly contaminated with various
      bacteria; this medium includes, in addition to the said recipe, 10 ng/1
      carbenicillin. Experiments and analysis of material from the patients
      demonstrated high sensitivity and inhibitory properties of NS media.

PMID- 7620784
TI  - [The biochemical indices of the saliva in children in a geoprovince with excess
      molybdenum].

PMID- 7620785
TI  - [The peroxidase activity of the blood serum in video display terminal workers].

PMID- 7620787
TI  - [An assessment of the absorptive function of the gastrointestinal tract by the
      iodometric indices of the saliva].

PMID- 7620786
TI  - [An effective biological tissue solvent].

PMID- 7620788
TI  - [The cytological characteristics of Malherbe's necrotizing epithelioma].

PMID- 7620789
TI  - [The cytological diagnosis of a benign lymphoepithelial tumor of a salivary
      gland].

PMID- 7620790
TI  - [Experience with the bacteriological diagnosis of tuberculosis at the dispensary
      and sanatorium stage of treatment].

PMID- 7620791
TI  - [Intracellular homeostasis and membrane permeability for calcium in essential
      hypertension].
AB  - Intracellular homeostasis of calcium was studied in patients with essential
      hypertension by two methods: calcium measurements using Lachema kits and study of
      the kinetics of interaction between chlortetracycline fluorescent probe and
      cellular membranes. Both the methods are highly sensitive, but they reflect
      different aspects of calcium homeostasis of the cells and supplement each other,
      and therefore should be used together to assess the severity of essential
      hypertension and monitor the therapy administered. The method of interaction of
      chlortetracycline with cellular membranes should be preferred as a more up-to
      date and informative.

PMID- 7620792
TI  - [The assessment of the ferritin level in gastroenterological diseases].
AB  - Blood serum ferritin levels were measured by indirect hemagglutination test in
      patients with diseases of the liver, bile duct, and gastrointestinal tract.
      Ferritin levels were found increased in the majority of patients, though to a
      different measure. Its concentrations were the highest in patients with virus
      hepatitis A, cirrhosis of the liver, and reactive nonspecific hepatitis,
      normalizing in the course of treatment, These data prompt the use of ferritin
      measurements in the diagnosis, monitoring the course of treatment, and prediction
      of the outcomes of acute and chronic diseases of the liver, bile duct, and
      gastrointestinal tract.

PMID- 7620793
TI  - [Those who took an oath to Hippocrates and aviation].

PMID- 7620794
TI  - [Aviation noise as an ecological environmental factor].
AB  - Average diurnal doses of noise, received by aviation engineers servicing up-to
      date aircrafts and living near air fields, were analyzed. The doses appeared to
      outnumber the normal values, especially during the work and the sleep. The
      examinees living in 1-2 km from air fields were proved to have significantly
      higher auditory thresholds for 1,000-8,000 Hz, in comparison with the examinees
      residing 5-6 km apart. The excessive noise associated with no occupational
      matters worsens the hearing restoration after the work, promotes accumulation of
      the hearing fatigue. Those facts were proved by experiments with audiometry and
      impedometry. The studies stressed the importance of aviation noise as ecologic
      factor.

PMID- 7620795
TI  - [Changes in specific sensation in pilots exposed to systematic general
      vibration].
AB  - Helicopter pilots exposed to excessive general vibration demonstrate changes of
      specific sensation (vibrotactile, vestibular, auditory), that could be signs of
      occupational disorder. Those changes are increased thresholds of vibrotactile
      sensation, lower vestibulovegetative stability, changed vestibulospinal reflexes,
      more common occurrence of consistent deafness for voice frequencies in comparison
      with jet aircraft pilots. Experimental vibration (50-1,800 (m/s2) 2 hour) caused
      no changes of the vibrotactile and auditory sensation, and the modified
      vestibular function could prove the increased vestibular reactivity.

PMID- 7620796
TI  - [Possibilities of psychotherapeutic and electrophysiological correction of
      psychosomatic disorders in pilots].
AB  - The authors necessitate elaboration and application of psychotherapeutic and
      electrophysiologic means and methods to improve functional state of pilots. Many
      experimental studies concerning the psychosomatic disorders, "complicated"
      psychic states in pilots, features of the etiology and the pathogenesis helped to
      define main directions of control and correction for necessary level of
      psychophysiologic resources and occupational performance in pilots.

PMID- 7620797
TI  - [Problems of flight safety and effectiveness of aviation specialists'
      activities].
AB  - In all cases reliability of aviation specialists' activities is a parameter
      influenced by complex of intrinsic and extrinsic matters. That proves the concept
      of absolutely safe flights to be inadequate, necessitates justification of the
      maximal safety level providing the reliability degree which is potentially
      available. The actual risk always exceeds the expected one, and the difference
      between them shows the resources and approaches to optimize aviation systems
      through more reliable specialists and equipment. Flight accidents have three
      groups of causes traced to human factor. The first group comprises social factors
      and peculiarities of pilots' and aviation supervisors' training. This group is in
      charge of nearly 50% of the accidents. The second group includes ergonomic
      drawbacks of the equipment and induces 25% of flight accidents. The third group
      covers medical and psychologic factors which show not only the pilot's health,
      but the functional resources tending to decrease during the activities. This
      group also causes about 25% of the accidents. If higher expenses for training of
      pilot causing the accident risk equal to 0.01, amount of flight accidents could
      decrease several times, and overall expenses will be optimal (nearly 2 times
      lower than now).

PMID- 7620798
TI  - [Interrelations between psychologic features of piloting and development of
      occupationally important mental traits].
AB  - The article covers some problems connected with adaptational changes in psychic
      and psychologic features of humans involved into pilot training. The authors
      present data on mutual influence of the psychic features, their changes and
      success in the pilot training, describe some specific mechanisms of psychologic
      features developing in connection with the training, express their point of view
      about determination and forecasting of the described phenomena influencing
      occupational health of pilots.

PMID- 7620799
TI  - [Maintenance of vitality and performance of pilots by means of oxygenation
      equipment complex in emergency depressurization of the cabin].
AB  - The authors studied efficiency of life supply by means of Oxygenation Equipment
      Complex (OEC) for pilots subjected to depressurization of the cabin in emergency
      on altitudes under 20 km. OEC provides breathing under the excessive oxygen
      pressure and light-weight ammunition. Efficiency of the complex was evaluated
      through polling the examinees, the time of the discomfort occurrence, changes of
      the cardiorespiratory and visual parameters, functional tests and quality of the
      piloting. The studies proved OEC to be effective means for saving the life and
      the performance maintaining when the depressurization of the cabin on altitudes
      under 20 km. The authors estimated "reserve time" for the pilot's performance
      maintaining within the altitudes of 14-16-18-20 km and revealed the factors
      delimiting efficiency of OEC in the studied conditions.

PMID- 7620800
TI  - [Method of forecasting maximal bearable time at low temperature for humans].
AB  - Theoretical and experimental studies helped to elaborate a method defining
      maximal time for humans to tolerate low ambient temperatures with consideration
      of the physical activity and clothing, wind speed. Methodic approaches suggested
      enable various services to forecast the maximal time for humans to tolerate low
      temperatures during the work in critical conditions.

PMID- 7620801
TI  - [Method of assessing the functional state of the human body].
AB  - The article demonstrates an algorithm to evaluate functional state of operators
      exposed to ecologic hazards. The evaluation of the functional state includes
      analysis of the heart rhythm registered for 2 minutes. The functional state is
      assessed through an Indicator of Regulatory Systems Activity (IRSA), obtained by
      summation of all the values in modulus. IRSA values define 5 functional states:
      norm; functional strain moderate, marked and extreme; asthenia of regulatory
      systems. The algorithm suggested differs from the known ones in some features as
      follows. The diagnosis of heterotopic arrhythmia serves for more precise code
      demonstrating the heart automatism; formed on the basis of variation coefficient,
      the code demonstrating stability of the regulation proves the status of stable or
      disordered regulation; the code demonstrating activities of subcortical neural
      centers is formed on the basis of measured relative capacity of primary and
      secondary respiratory waves.

PMID- 7620802
TI  - [Methods and software of the assessment of risk of untoward outcome after
      exposure to critical occupational factors].
AB  - The authors discuss a problem of expert PC systems helpful in evaluation of lower
      performance of operators exposed to extreme factors of the environment. Those
      extreme factors are exemplified by increased G-factor during maneuver flights.
      Some empirical principles obtained by means of trials on the real and half-real
      testing units helped to design mathematic tools to evaluate risk of pilots'
      subconsciousness episodes, so a criterion scale of the subconsciousness risk is
      suggested. Particular values of the risk level are associated with operative and
      long-standing recommendations to make the risk lower. The materials and data used
      are examples of linguistic variables and fuzzy-set theory, applied to unfavorable
      outcomes in occupational risk.

PMID- 7620803
TI  - [Physiological bases of the use of impulse currents in central electric
      neuroregulation].
AB  - The article gives basic science for application of impulse current to central
      neuroregulation in occupational physiology and physical training medicine.
      Analysis of fundamental works contributed by distinguished professionals in brain
      physiology and the personal experimental data helped to elaborate a medical
      technology of central electric neuroregulation (CELNER), the associated
      methodology and equipment. The studies proved efficiency of devices "LENAR" and
      "micro-LENAR" used for restoration of occupational performance in operators and
      for treatment of premorbid disorders of central nervous and cardiovascular
      systems. The authors defined ways to put the CELNER method into the medical
      practice for aviation, marine and physical training.

PMID- 7620804
TI  - [Several mechanisms of immune response of humans exposed to critical factors in
      piloting].

PMID- 7620805
TI  - [Functional state of the operator exposed for a long time to environmental
      factors in a single-cabin aircraft].

PMID- 7620807
TI  - [Ecological aspects of aviation ergonomics].
AB  - The authors analyzed human role in ecologic system, using the principle "human-
      environment--health", and human function in ecologic and ergonomic system, using
      the principle "operator--environment--occupational reliability" for aviation
      ergonomics. Unfavorable ecologic environment influencing the operator was
      considered a complex stress factor composed of objective environmental and
      emotional elements. The authors describe human response to physiologically
      adequate and inadequate stress factors. The article stresses good prospects
      associated with application of aviation ergonomics to targeting some problems.

PMID- 7620806
TI  - [General occupational analysis of activities of aviation specialists].

PMID- 7620808
TI  - Growth of untreated and radiation-damaged Listeria as affected by environmental
      factors.
AB  - The growth of untreated Listeria monocytogenes 4ab No. 10 and that of the
      surviving fraction of its population treated with 0.8 kGy gamma rays was
      investigated in a microtitreplate system at incubation temperatures between 3
      degrees C and 35 degrees C in Tryptic Phosphate Broth (TPB) or Brain Heart
      Infusion Broth (BHIB) media containing NaCl between 0.25 to 16.75% (w/v), and
      acidified with citrate-phosphate buffers to pH values between 4.63 and 7.06. The
      initial viable count was 3 x 10(3)/ml. Time periods to visible growth were
      recorded. Radiation survivors showed increased salt- and pH-sensitivities and
      increased minimum temperature for growth in TPB-based media. Adverse effects of
      sub-optimal environmental factors (reduced water activity, pH and temperature)
      and radiation injury were much less pronounced in BHIB-based media. Polynomial
      equations describing the combined effects of hydrogen ion and salt concentrations
      on the detectable growth at 30 degrees C were constructed for quantitative
      assessment of interactions. The results demonstrate that combining environmental
      stresses with low-dose irradiation can control growth of L. monocytogenes.

PMID- 7620811
TI  - Epifluorescent microscopy of earthworms' intestinal bacteria.
AB  - Epifluorescent microscopy was employed to compare the bacterial live counts (BC)
      in the gut of two earthworm species Aporrectodea caliginosa and Lumbricus
      rubellus, representing different ecophysiological groups. The average number of
      BC was 10.9 x 10(9) g-1 dry weight in the gut of A. caliginosa, 5.9 x 10(9) in
      that of L. rubellus, 8.1 x 10(9) in earthworm casts and 6.0 x 10(9) in the soil.
      The number of BC showed a great seasonal variability in all the materials
      studied, exhibiting maxima in spring and autumn, and a minimum in summer. The BC
      increased in number during the passage of food material through the gut of both
      L. rubellus and A. caliginosa. The difference between BC in fore-gut and hind-gut
      were significantly higher in L. rubellus (4.2 x 10(9) vs. 8.8 x 10(9)) than that
      in A. caliginosa (10.3 x 10(9) vs. 13.4 x 10(9)). Interspecific differences in
      the number of BC may result from the different chemical and microbiological
      composition of the material consumed by earthworms as related to different
      feeding habits of both species.

PMID- 7620809
TI  - Production and some characteristics of beta-glucosidase in Diaporthe (Phomopsis)
      helianthi.
AB  - Diaporthe (Phomopsis) helianthi Munt.-Cvet. et al. is an important
      phytopathogenic fungus which causes stem canker of sunflower. When grown in
      submerged cultures in the presence of milled wheat chaff as a carbon source this
      phytopathogen produced extracellular and intracellular beta-glucosidases. The
      optimum pH of these enzymes was 4.8. The temperature of crude intracellular beta
      glucosidase activity was at 60 degrees C, whereas the optimum activity of crude
      extracellular beta-glucosidase was observed in a wide range of temperature
      between 40 and 70 degrees C. Although, extracellular and intracellular beta
      glucosidase activities had identical pH and similar temperature optima, the
      thermal stability of the intracellular enzyme was significantly higher.

PMID- 7620810
TI  - B cell specific natural IgM autoantibodies: multifunctional regulators of the
      humoral immune response (a review).

PMID- 7620812
TI  - Bacteria adherent to the hindgut of terrestrial isopods.
AB  - The gut microflora of three terrestrial isopod species was investigated by means
      of scanning electron microscope. The gut cuticle of intermoult specimens of
      Ligidium hypnorum and Porcellio scaber was densely colonized with bacteria. Some
      moulting specimens of the same species were observed with the guts free of
      bacteria. In all investigated specimens of Hyloniscus riparius the guts were
      completely free of microflora. In this case our finding could not be interpreted
      in relation to the moulting stage of the animal.

PMID- 7620813
TI  - Hybrid process for ethanol production from rice straw.
AB  - A hybrid process for the fermentation of rice straw hydrolysates into ethanol was
      designed to simultaneously utilize cellulose and hemicellulose fractions of the
      agro-residue. The process involved dilute acid hydrolysis (for obtaining C-5
      sugars) followed by enzymatic saccharification of cellulose enriched fraction
      with crude cellulase produced by mixed cultures of Trichoderma reesei Rut C-30
      and Aspergillus ochraceus IMI 317911. The fermentation medium containing acid and
      enzymatic hydrolysate mixture of pentoses and hexoses monomers was fermented with
      yeast coculture of Saccharomyces cerevisiae and Pachysolen tannophilus resulting
      in 295.0 ml ethanol/kg of rice straw. The hybrid process resulted in an efficient
      utilization of both cellulosic and hemicellulosic components of the rice straw
      for ethanol production.

PMID- 7620814
TI  - Effect of some environmental factors on Rhizobium and Bradyrhizobium strains.
AB  - Effects of different abiotic factors (acidity, salinity, nitrate and temperature)
      on growth rate of root-nodule bacteria (Rhizobium and Bradyrhizobium) strains
      were investigated in vitro. Strains isolated from Vicia faba L., Coronilla varia
      L. and Lupinus albus L. exhibited a large variation in tolerance of the above
      mentioned factors. These bacteria should be screened under stimulated conditions
      for enhanced survival before selection to be used for commercial inoculant
      production. Linear correlation matrix data were useful to find the appropriate
      concentrations for the selection of the tolerant strains.

PMID- 7620815
TI  - Simultaneous saccharification and fermentation of rice straw into ethanol.
AB  - The physicochemical pretreatment of ball milled rice straw with different
      oxidizing agents, peracetic acid, alkali-peroxide, manganese-peroxide compounds
      under steaming pressure were studied. The pretreatment resulted in major changes
      in chemical composition of rice straw. The peroxide treated substrates were found
      to be most susceptible to enzymatic saccharification. A maximum saccharification
      (77.4%) of alkaline-peroxide treated rice straw (5%, w/v) was achieved using
      cellulase enzyme produced by mixed cultivation of Trichoderma reesei Rut C-30 and
      Aspergillus ochraceus containing 1.83 FPU, 1.63 cellobiase and xylanase 2.03
      IU/ml. The hydrolysate was fermented using coculture of a temperature resistant
      strain of Saccharomyces cerevisiae and Pachysolen tannophilus resulting in 1.5%
      (w/v) ethanol. The SSF of 10.0% (w/v) H2O2-MnSO4 treated straw yielded maximum
      ethanol (2.9%, w/v) after 72 h at 40 degrees C. As a consequence of the well
      balanced cellulase production by mixed fungal culture, the supplementation of
      cellobiase or xylanase was not necessary in the simultaneous saccharification and
      fermentation process.

PMID- 7620817
TI  - Diversity in the antigenic structure of different hexon types among the members
      of adenovirus subgenus D.
AB  - Antigenic relationships of human adenovirus (Ad h) hexon types: 8, 9, 10, 13, 19,
      26, 27 and intermediate type 9/13 (I13), belonging to subgenus D were studied
      with 61 hybridoma ascitic fluids containing monoclonal antibodies (MAbs). The
      MAbs were produced in three different panels directed against Ad h1, Ad h35, and
      bovine Ad type 2. The reactivity pattern (RP) and the degree of cross-reactivity
      (CR) of the MAbs were determined in indirect ELISA. By the 61 MAbs 8 different
      RPs could be distinguished. The distinct RPs of hexon types of 8, 9, 10, I13 and
      19 were identical or nearly identical and the occurrence of the different eight
      RPs were based mainly on the combinations of positive or negative reactions of
      different MAbs with the hexon prototypes 13, 26 and 27. According to the
      different RPs and to the number of reacting and non-reacting MAbs with the
      different hexon types as well as on the base of the degree of CR three groups of
      hexon types with diverse antigenic structure could be distinguished. These data
      revealed the existence of remarkable diversity in the antigenic structure between
      type 27 and types 8, 9, 10, I13 and 19, as well as an intermediate position of
      prototypes 13 and 26.

PMID- 7620816
TI  - HLA associated cytotoxic antibody production in dialyzed chronic uraemic
      patients.
AB  - We studied the level of the cytotoxic anti-HLA antibodies (CTA) in 90
      hemodialyzed chronic uraemic patients who were on waiting list of
      transplantation. An association between alleles of HLA A1, B8, DR3 haplotype and
      the level of CTA was studied. The ratio of the reduced CTA producing subjects was
      significantly higher in the HLA B8 and DR3 carriers. We could observe the highest
      ratio in the joint appearance of these alleles. In the presence of HLA A1 allele
      the ratio was decreased beside B8 or DR3 even as joined attendance of these
      alleles. Our data suggest a different role of these linked antigens in the
      regulation of cytotoxic antibody production.

PMID- 7620818
TI  - Gq/11 communicates with thromboxane A2 receptors in human astrocytoma cells,
      rabbit astrocytes and human platelets.
AB  - Western blot analysis was performed to clarify the presence of trimeric G protein
      subfamily in membranes derived from human astrocytoma cells (1321N1), cultured
      rabbit astrocytes and human platelets, using G protein antisera GS alpha, Gi
      alpha, Gq/11 alpha, and G beta were found to exist in membranes derived from
      human astrocytoma cells and rabbit astrocytes as well as human platelets.
      However, only small amount of G(o) alpha was detected in any membranes. Gq/11
      alpha was expressed much more in human platelets than in human astrocytoma cells
      or rabbit astrocytes. 9,11-Epithio-11,12-methanothromboxane A2 (STA2), a stable
      analogue of thromboxane A2 (TXA2), activated GTPase in membranes derived from
      human astrocytoma cells, rabbit astrocytes and human platelets with different
      potencies. STA2-induced GTPase activation in human platelet membranes was partly
      inhibited by treatment with QL antibody at 0 degrees C for 90 min. Furthermore,
      STA2-induced GTPase activation in membranes derived from human astrocytoma cells
      and rabbit astrocytes were potently inhibited by treatment with QL antibody. The
      results obtained indicate that TXA2 receptors in human astrocytoma cells and
      rabbit astrocytes communicate with Gq/11 as well as in human platelets.

PMID- 7620819
TI  - Changes in protein kinase C activity, subcellular distribution and protein
      phosphorylation during the lactogenic cycle in the rat mammary tissue.
AB  - Direct and indirect evidence emphasizes the participation of classical protein
      kinase C (cPKC) in the development and function of the mammary gland. This work
      shows that there are changes not only in total cPKC activity during the
      lactogenic cycle, but also in the relative amounts of the soluble and particulate
      cPKC activities and that the time-course of these two events are not the same.
      The time-course of translocation from the cytoplasm to the plasma membrane
      suggests that the soluble and particulate forms of the enzyme may be associated
      with growth and differentiation of the tissue, respectively. Phosphorylation
      patterns also show characteristic and significant differences throughout the
      development of the gland. These results suggest that both total mammary cPKC
      activity and its subcellular forms change in accordance with the proliferative
      and differentiative stages of the mammary gland, and that the enzyme
      translocation occurs during the transition from pregnancy to lactation.

PMID- 7620820
TI  - Inhibitory effect of FUT-175 on the production of interleukin 8 and
      polymorphonuclear leukocyte elastase.
AB  - We investigated the inhibitory effects of a protease inhibitor, FUT-175, on the
      production of interleukin 8 (IL-8) and polymorphonuclear leukocyte elastase
      (PMNE) by polymorphonuclear leukocytes (PMN) and vascular endothelial cells. IL-8
      production by PMN and vascular endothelial cells stimulated with
      lipopolysaccharide (LPS) was inhibited by FUT-175. This compound also inhibited
      PMNE production by PMN following LPS stimulation.

PMID- 7620821
TI  - Transfer of copper and zinc from ionic and metallothionein-bound forms to Cu, Zn-
      superoxide dismutase.
AB  - Reactivity in transfer of copper (Cu) and zinc (Zn) to their binding sites of
      superoxide dismutase (SOD) was examined in vitro by the HPLC/atomic absorption
      spectrophotometry. Ionic Cu (cuprous and cupric ions) were incorporated more
      efficiently than the metal bound to metallothionein. Cu binds not only to the Cu
      binding site but also to the Zn-binding site. Although Zn in the reaction medium
      and the metal bound to the Zn-binding site of SOD affected little the reactivity
      in binding of ionic Cu, they disturbed the reactivity of Cu bound to
      metallothionein to the Cu-binding site. Both ionic and metallothionein-bound Zn
      were transferred at a comparable efficiency to the Zn-binding site but not to the
      Cu-binding site. Co-existing ionic Cu but not metallothionein-bound Cu in the
      medium inhibited the binding of Zn to SOD. The results indicate that ionic Cu can
      be transferred to both Cu- and Zn-binding sites of SOD more efficiently than
      metallothionein-bound Cu, while both ionic and metallothionein-bound Zn are
      transferred only to Zn-binding site at a comparable efficiency.

PMID- 7620822
TI  - EDTA and EGTA can discriminate tonic contractions induced by thromboxane A2 and
      phorbol ester in rabbit aortic smooth muscles.
AB  - The effects of chelating agents of divalent cations on the contraction induced by
      STA2, a stable thromboxane A2 analog, were examined in rabbit aortic smooth
      muscles, comparing with a phorbol ester-induced contraction. Pretreatment of
      muscles with EDTA (4 mM) resulted in potent inhibition of STA2 (1 nM)-induced
      contraction. However, STA2 could contract muscles slowly in the presence of EGTA
      (4 mM). The muscles contracted with STA2 relaxed rapidly after addition of EDTA
      and/or EGTA. However, STA2 recovered contraction in the presence of EGTA, but not
      of EDTA. PDBu, phorbol 12,13-dibutyrate, also contracted the muscles slowly and
      potently. Pretreatment with EDTA, but not EGTA, attenuated PDBu-induced
      contractions. The muscles contracted with PDBu relaxed after the addition of
      EDTA, but not of EGTA. The present results imply that the vascular smooth muscle
      contractions are composed of two distinct components: a short-lived contraction
      that is related to Ca2+ and a lasting contraction that is related to Mg2+, and
      EDTA and EGTA are good tools for discriminating the tonic phase of STA2- and/or
      PDBu-induced contraction.

PMID- 7620823
TI  - Effects of verapamil on hepatic glutathione in the rat.
AB  - Effects of verapamil, an calcium channel blocker, on hepatic glutathione were
      studied in vivo in the rat and in the perfused rat liver. An injection of
      verapamil at a dose of 15 mg/kg body weight but not at 5 mg/kg significantly
      decreased hepatic glutathione contents in both fed and fasted animals 6 h after
      the injection. The administration of verapamil at a dose of 10 mg/kg twice a day
      for a week brought a significant decrease in hepatic glutathione contents and a
      significant increase in plasma glutathione levels. In the perfused rat liver,
      sinusoidal glutathione efflux was significantly increased when verapamil was
      added to the perfusion medium in a concentration of 20 microM. These data
      indicate that verapamil increases glutathione efflux from the liver and that
      calcium mobilization may be concerned in glutathione efflux in vivo.

PMID- 7620824
TI  - Activation of GABA-A receptor by hypotensive drugs.
AB  - Chronic antihypertensive treatment with clonidine and beta-adrenoceptor blockers
      leads to a significant increase in GABA-A receptor number in the hypothalamus,
      the pons-medulla and the striatum. The enhancement of receptor number after two
      beta-blockers was associated with the decrease of Kd factor in the pons-medulla
      and the striatum. There was no change in receptor affinity after clonidine. We
      conclude that neurotransmission via GABA-A receptors is important for the
      hypotensive effects of clonidine and some beta-adrenoceptor blockers.

PMID- 7620825
TI  - Regulation of daily rhythm of body temperature by neurotensin receptor in rats.
AB  - It is proposed that neurotensin receptor mediated signal transduction may play an
      important role in the thermoregulatory control in the brain. In this study, a
      significant increase in body core temperature was observed with SR 48692, a
      neurotensin receptor antagonist, after treatment of rats at light phase when the
      temperature is regulated low. On the other hand, SR 48692 delayed the
      physiological decline of body core temperature at dark phase when the temperature
      is highly regulated. We also found slight daily rhythmicity, though not
      significant, in neurotensin/neuromedin N precursor protein mRNA levels in the
      medial preoptic nucleus using in situ hybridization technique. Our results
      support the hypothesis that endogenous neurotensin receptor agonists play a
      physiological role in the central modulation of body core temperature in rats.

PMID- 7620826
TI  - Developmental change of kidney dopamine receptors in spontaneously hypertensive
      rats.
AB  - To elucidate the role of the kidney dopamine system on blood pressure regulation,
      we investigated the developmental change of kidney dopamine receptors in
      spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. The
      autoradiogram of [3H]-SCH23390, a specific DA1 receptor antagonist, showed that
      DA1 receptors were localized mainly in the rat renal cortex. The radiolabeled
      receptor assay (RRA) of [3H]-spiperone was performed on 3-, 7-, and 18-week-old
      SHR using the homogenate of renal cortex. Neither dissociation constant (Kd) nor
      maximum binding capacity (Bmax) were different between SHR and WKY rats at the
      age of 3 and 7 weeks. Nevertheless, Kd and Bmax were significantly low in 18-week
      old SHR. The systolic blood pressure of 7-, and 18-week-old SHR was significantly
      higher than that of age matched WKY rats. The urinary dopamine excretion in 16
      week-old SHR was significantly higher than that in age-matched WKY rats, although
      urine volume and urinary sodium excretion were the same as those in the control
      in both sodium-loaded and -restricted state. In summary, although renal dopamine
      production was enhanced in SHR in the hypertensive state, dopamine was found not
      to contribute to natriuresis since the number of dopamine receptors was reduced
      in these rats. We also found that enhanced dopamine production in response to a
      salt load was lacking in these rats. These two pathological phenomena noted in
      the renal dopamine system play a role in the progression of hypertension in SHR.

PMID- 7620827
TI  - Endogenous gamma-interferon activates thymidine phosphorylase in colorectal
      cancer tissue.
AB  - We measured neopterin (NPT), an indirect marker of gamma (gamma)-interferon, and
      the activity of thymidine phosphorylase (dThdPase) in the advancing front of
      colorectal carcinoma and in normal mucosa. Cancer showed a higher concentration
      of NPT than normal mucosa and also showed significantly higher (p < 0.0001)
      dThdPase activity than normal mucosa. There was a strong correlation between NPT
      concentration and dThdPase activity in cancerous and normal mucosa. These results
      suggest that endogenous gamma-interferon could activate dThdPase activity, which
      is essential to nucleic acid metabolism because it regulates the availability of
      thymidine.

PMID- 7620829
TI  - Antibody transformation by peroxynitrite as determined using capillary
      electrophoresis: a feasibility study.
AB  - Peroxynitrite may be a physiologically relevant endogenous neurotoxin that forms
      following CNS trauma when excessive levels of NO and .O2 accumulate. Recently,
      peroxynitrite was found to inactivate the polyclonal antibody to cAMP. A
      feasibility study was performed to evaluate the use of capillary electrophoresis
      as an effective tool regarding the structural transformation of antibody
      following exposure to peroxynitrite with or without co-incubation with a
      peroxynitrite scavenger. A polyclonal antibody to cAMP and a monoclonal antibody
      to plasminogen activation inhibitor-1 were exposed to peroxynitrite with or
      without penicillamine coincubation. Samples were analyzed by an Applied
      Biosystems analytical capillary electrophoresis system, model 270A. Initial
      examination of the peroxynitrite scavenger penicillamine and its reaction with
      peroxynitrite showed a penicillamine migration peak at about 9.1 min and a
      presumed s-nitro adduct of penicillamine that migrated at 10.9 min. Exposure of
      either antibody to peroxynitrite resulted in structural transformation of protein
      based on changes in migration patterns. In addition, co-incubation with
      penicillamine prevented this transformation and preserved the pre-peroxynitrite
      migration patterns of antibodies. In cases of antibody reaction, s-nitro adduct
      formation could be simultaneously monitored. We found capillary electrophoresis
      to be ideally suited to this type of analysis. With capillary electrophoresis, we
      were able to simultaneously monitor the effects of peroxynitrite on large
      proteins and a small scavenger molecule. As a result, a complete record of the
      reaction was obtained within a single 15-min analysis period.

PMID- 7620830
TI  - Active oxygen generated in the process of carcinogen metabolism can induce
      oxidative damage in nuclei.
AB  - In the present study, we examined whether active oxygen formed in the process of
      4-nitroquinoline 1-oxide (4NQO) reduction by DT-diaphorase could induce oxidative
      stress on the pulmonary nuclei. The rapid production of OH- radical-like species
      after the start of the 4NQO reduction was observed, and subsequent induction of
      nuclear lipid peroxidation occurred. In conjugation with this event, DNA damage
      estimated as DNA single strand breaks (DNA-SSB) increased in a time-dependent
      manner. The induction of this DNA damage was partially inhibited by mannitol or
      vitamin E treatment. These findings suggest that the active oxygen generated in
      the process of the 4NQO reduction can induce oxidative damage on the pulmonary
      nuclei.

PMID- 7620828
TI  - Testing lazaroids U-74389G and U-83836E for therapeutic value in experimental
      allergic encephalomyelitis in the Lewis rat.
AB  - Reactive oxygen intermediates (ROI) and reactive nitrogen intermediates (RNI) are
      toxic molecules that are thought to play a pathogenic role in many disease
      states, and data from prior studies indicate a role for ROI and RNI in the
      pathogenesis of experimental allergic encephalomyelitis (EAE). ROI and RNI can
      elicit tissue damage by initiating the chain reaction of lipid peroxidation.
      Lazaroids are a series of compounds that have been shown to interrupt lipid
      peroxidation. In the present study, the lazaroids, U-74389G and U-83836E, were
      administered to Lewis rats with EAE in order to evaluate their therapeutic
      effectiveness. Several different doses and administration routes, which were
      based on the manufacturer's (Upjohn) recommendations and a prior experimental
      study, were employed: 1) intraperitoneal injection (IP), 1mg drug/kg body weight,
      1x/day from 7-18 days postencephalitogen injection (diseases onset approximately
      9 day), male; 2) IP, 1mg/kg, 1x/day from 0-18 days, male; 3) intravenous (IV)
      cannula, 3mg/kg, 2x/day from 7-18 days, female; 4) IV cannula, 3mg/kg, 2x/day
      from 7-18 days, male; and 5) IV cannula, 10mg/kg, 2x/day from 7-18 days, female.
      The weights and clinical signs were evaluated on a daily basis. In all treatment
      regimens, there was an absence of a statistically significant difference between
      the vehicle-treated animals and the two groups of drug-treated animals. These
      data imply that lipid peroxidation may not be an effective therapeutic site in
      EAE. It is important to note that there are several different types of EAE and
      our study only explored the EAE model in the Lewis rat.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7620831
TI  - An acute phase response does not elevate rat heart metallothionein levels, nor
      inhibit adriamycin toxicity.
AB  - An acute phase response, a group of adaptations to some types of stress, blocks
      injury in rodents due to hepatotoxins and agents generating arthritis-like
      inflammation. In contrast, this study found no protection against adriamycin
      induced acute cardiotoxicity in rats. The acute phase response was initiated by
      turpentine-stimulated leg inflammation. Injury was assessed by survival,
      macroscopic signs of injury, and heart lipid peroxidation. Acute phase response
      produced the expected rises in the stress-responsive proteins: serum
      ceruloplasmin and liver metallothionein. However, cardiac metallothionein was
      unaffected. These results suggest that an acute phase response will not
      necessarily protect tissues where levels of stress-induced proteins are not
      raised.

PMID- 7620832
TI  - Growth phase in relation to the lethal action of tamoxifen on Candida albicans.
AB  - Tamoxifen, a drug used to treat breast cancer, might have antifungal potential.
      The fungicidal activity of tamoxifen against Candida albicans surpassed that of
      the most active of the imidazole-type drugs. At 15-20 microM, tamoxifen rapidly
      killed yeast cells in stationary phase as well as in logarithmic phase, whereas
      imidazoles at this level generally do not exert significant lethal activity
      against stationary phase organisms.

PMID- 7620833
TI  - Effect of phenobarbital, spironolactone and pregnenolone-16 alpha-carbonitrile on
      rat hepatic beta-glucuronidase.
AB  - beta-Glucuronidase cleaves beta-glucuronides of drugs, steroids, as well as
      macromolecular compounds containing glucuronic acid bound with a beta-glycoside
      bond. Therefore, the study of induction of this enzyme by known microsomal enzyme
      inducers is of obvious interest. The effect of phenobarbital, spironolactone and
      pregnenolone-16 alpha-carbonitrle on the rat liver beta-glucuronidase was
      studied. These compounds augmented the activity of this enzyme, in the above
      increasing order. These results are discussed in view of the influence on
      pharmacokinetics of many drugs. Furthermore, they may lead to new therapeutic
      approaches for certain diseases.

PMID- 7620834
TI  - Metabolism of 3-acetylcoumarin in rat 9000xg supernatant fraction (S-9)and
      baker's yeast.
AB  - In the incubation of 3-acetylcoumarin in rat liver supernatant fraction (S-9),
      four metabolites were isolated, and two of which were inseparable diastereomeric
      mixture as a major product. However, when 3-acetylcoumarin was fermented with
      baker's yeast (Saccharomyces cerevisiae), only two compounds were obtained as the
      same as the above mixture. The structures of those metabolites were confirmed by
      NMR and Mass spectra. However, the above metabolites in rat 9000xg supernatant
      fraction were not induced by phenobarbital, nor inhibited with SKF-525A at all.

PMID- 7620835
TI  - Effect of losartan, an AT1 selective angiotensin II receptor antagonist, on
      isoproterenol-induced cardiac ornithine decarboxylase activity.
AB  - Ornithine decarboxylase (ODC,EC 4.1.1.7), a rate-limiting enzyme in polyamine
      biosynthesis, is known to be induced by a beta-adrenoceptor agonist,
      isoproterenol (ISO). ODC activity and cardiac polyamine content are considered to
      be correlated with ISO-induced cardiac hypertrophy in rat hearts. To determine
      whether ISO-induced cardiac ODC activity is mediated through the renin
      angiotensin system, especially at the AT1-receptor, we used a nonpeptide AT1
      receptor antagonist, losartan, in this study. Losartan (10 mg/kg) suppressed both
      heart ODC and polyamine contents in ISO-treated rats. Although metoprolol (a
      selective beta-adrenoceptor antagonist) totally suppressed ODC activity, these
      results suggest that ISO-stimulated cardiac ODC activity may be regulated through
      beta 2-adrenoceptors coupled with AT1 receptors in rats.

PMID- 7620836
TI  - Dose and species dependent pharmacokinetics of a novel sigma receptor antagonist,
      DuP 734.
AB  - The pharmacokinetics of a novel sigma receptor antagonist, DuP 734, was evaluated
      in mice, rats, beagle dogs and cynomolgus monkeys at various intravenous and oral
      doses utilizing a specific reversed-phase HPLC assay. Following intravenous
      dosing, the disposition of DuP 734 in all species was characterized by high total
      body systemic plasma clearance (46 to 87 ml/min/kg) and large steady-state volume
      of distribution (3.6 to 6.8 l/kg). The terminal elimination half-life ranged from
      50 to 83 min. The gastrointestinal absorption from an aqueous solution was very
      rapid in mice and rats with peak DuP 734 plasma concentrations attained within 5
      and 20 min following administration, respectively. The peak plasma concentrations
      in dogs and monkeys were attained within 45 and 130 min, respectively. The
      absolute bioavailability in mice ranged from 29 to 46% at doses of 3.1 to 30.1
      mg/kg. The bioavailability increased from 4 to 10% and from 14 to 72% when doses
      were increased from 12.5 to 50 mg/kg and 1 to 3 mg/kg of DuP 734 in rats and
      dogs, respectively. The bioavailability in monkeys was 30.5% at 9.3 mg/kg DuP 734
      dose. The dose dependent pharmacokinetics of DuP 734 was observed within narrow
      dose ranges in all animal species investigated.

PMID- 7620837
TI  - Effect of TJ-96, an anti-allergic herbal medicine, on tracheal transepithelial
      potential difference in vivo.
AB  - We studied the effect of Saiboku-to (TJ-96), an anti-allergic herbal medicine, on
      transepithelial potential difference of rabbit trachea and possible involvement
      of nitric oxide (NO) generation in vivo. Perfusion of TJ-96 on the tracheal
      mucosal surface increased PD in a concentration-dependent manner, the maximal
      increase from the baseline level and the concentration of TJ-96 required to
      produce a half-maximal effect (EC50) being 8.1 +/- 1.4 mV (mean +/- SE, P <
      0.001) and 47 micrograms/ml. This effect was abolished by pretreatment with the
      Na channel blocker amiloride. NG-nitro-L-arginine methylester (L-NAME) but not NG
      nitro-D-arginine methylester (D-NAME) inhibited TJ-96-induced increase in PD, and
      this inhibition was selectively reversed by L-arginine. These results suggest
      that TJ-96 stimulates Na absorption by airway epithelial cells probably through
      NO generation.

PMID- 7620838
TI  - Binding of fosphenytoin, phosphate ester pro drug of phenytoin, to human serum
      proteins and competitive binding with carbamazepine, diazepam, phenobarbital,
      phenylbutazone, phenytoin, valproic acid or warfarin.
AB  - The protein binding of [14C]fosphenytoin, (3-phosphoryloxy-methyl phenytoin
      disodium), a phosphate ester prodrug of phenytoin sodium, to human serum
      proteins, serum albumin and alpha 1-acid glycoprotein was determined by
      ultrafiltration. The mean +/- SD% of fosphenytoin bound to human serum proteins
      was 95.7 +/- 0.48%. Binding to albumin (36.5 mg/ml) decreased linearly from 89.2
      to 67.3% when the fosphenytoin concentration was increased from 6 to 200
      micrograms/ml. Fosphenytoin was weakly bound to alpha 1-acid glycoprotein
      (13.3%). Simultaneous incubation with high concentrations of carbamazepine (10
      micrograms/ml) and diazepam (5 micrograms/ml) or therapeutic concentrations of
      phenytoin (10 micrograms/ml) had no effect on the binding of fosphenytoin to
      human serum proteins. High concentrations of phenobarbital (160 micrograms/ml),
      phenytoin (50 micrograms/ml), or valproic acid (500 micrograms/ml), however,
      caused slight, but significant, increases in the free fraction of fosphenytoin in
      serum protein. Phenylbutazone and sulfisoxazole resulted in a 48% increase in
      fosphenytoin free fraction while warfarin had a slight (8%), but significant,
      increase in free fraction of fosphenytoin. It was concluded that the
      concentration of albumin was the most important determinant for the plasma free
      fraction of fosphenytoin in man. Potential increase in fosphenytoin clearance may
      be observed in hypoalbuminemia.

PMID- 7620840
TI  - Calcitriol analogs cause differentiation of neoplastic cells in culture.
AB  - Several investigators are developing calcitriol (DHCC, Compound A) derivatives
      which have less effect on mineral metabolism and are effective in causing
      differentiation of neoplastic cells. In the present study we investigated three
      new DHCC derivatives (Compounds B, C, D) for differentiation inducing effect in
      human neoplastic cell lines HL-60 and U-937.

PMID- 7620839
TI  - Experimental model of cirrhosis in rabbits exposed to carbon tetrachloride by
      inhalation.
AB  - Orthotopic hepatic transplantation is the most diffused surgical treatment used
      when attempting to substitute an irreversibly damaged liver. However, this
      practice faces two main problems. Firstly, surgeons need to explant the organ
      from the donor who is a just deceased human being, with all the implications
      involved. Secondly, the host patient must be rendered immunologically tolerant to
      the graft, through pharmacological suppression. Some hepatic alterations allow a
      structural and functional compensation by means of an autotransplant, but liver
      cirrhosis, which is widely diffused in humans and easily produced in experimental
      animals, has not yet been treated with this technique. This research was
      undertaken with the aim of procuring hepatic cirrhosis in a medium-sized animal-
      the rabbit--exposed for some months to CCl4 vapours. Preliminary experiments were
      performed in order to shorten the challenge period by means of liver induction.
      This approach was unsuccessful because of the natural susceptibility of this
      species, which was heightened by the barbiturate administration (0.05% sodium
      phenobarbital in drinking water, for one week). However, induction, rendered
      impossible the survival after carbon tetrachloride given orally (125
      microliters/kg body weight) or by inhalation (1000 ppm for 2 hours). Finally,
      CCl4 was administered to normal rabbits by inhalation at the initial
      concentration of 100 ppm, for 2 hours twice a week. The level of the hepatotoxin
      was subsequently raised stepwise, according to the body weight curve, up to the
      maximum of 600 ppm by week 23. At the fourth week of intoxication, the metabolic
      activity of liver microsomes appeared severely depressed, as shown by the 300%
      increase of hexobarbital sleeping time. The observation of the surface of liver
      in situ, performed through an explorative laparatomy, showed initial but clear
      signs of hepatic fibrosis. At sacrifice, after six or ten months of cirrhogenic
      treatment, the histopathology examination of the liver demonstrated severe and
      massive cirrhosis, respectively for the two different steps. This experimental
      schedule appears to be suitable for producing hepatic cirrhosis in a medium-sized
      animal, which could be used as a model for pioneering attempts of liver
      autotransplantation. Furthermore, we point out two important aspects of these
      results. First, the poison has been inhaled by the experimental animals as it
      generally happens for humans in the environment. Second, the ratio between the
      length of exposure versus the life span of rabbits--6 months and 8 years,
      respectively--parallels that reported for human cirrhosis due to halogenated
      hydrocarbons--5 or 10 years versus 60 or 80 years.

PMID- 7620842
TI  - Limitations of zinc and metallothionein accumulation in rat livers following zinc
      administration.
AB  - In order to study whether or not there is a limit of zinc accumulation in livers
      of zinc-injected rats and establish the biosynthesis relationship of
      metallothionein by zinc, I examined the accumulated amount of zinc in rat liver
      after injection of ZnSO4 and the relationship between zinc and metallothionein
      contents in rat livers. Each rat was injected intraperitoneally once with 0.9%
      NaCl or zinc (10, 20, 40 or 60 mg zinc/kg b.w.) and was killed 14 h after
      injection. The distribution profiles of the hepatic cytosols of rats on a
      Sephadex G-75 column showed that the increased amounts of zinc were attributable
      to the metallothionein fraction. The zinc content in liver reached a maximum
      concentration of approx. 125 micrograms/g liver, corresponding to a dose (40 mg
      zinc/kg b.w.). These data suggested that there was a limit of zinc (essential
      metal) accumulation in livers of zinc-injected rats. The present results
      confirmed that the relative induction ability of metallothionein was mainly
      dependent on the metal content of the liver.

PMID- 7620843
TI  - Social categorization and group homogeneity: changes in the perceived
      applicability of stereotype content as a function of comparative context and
      trait favourableness.
AB  - Using the Katz-Braly checklist subjects (N = 65) assigned five traits to a
      national group and estimated the percentage of group members who had those
      traits. This was either an in-group (Australians) or an out-group (Americans),
      and subjects either judged that group alone (one-group conditions) or also
      estimated the percentage of people from the other nation (the United States or
      Australia, respectively) who had those same traits (two-group conditions). Across
      one-group conditions there was a significant out-group homogeneity effect with
      traits being seen to apply to more Americans than Australians, but there was no
      such effect across the two-group conditions. These findings were predicted on the
      basis of self-categorization theory's analysis of the role of comparative context
      in determining level of social categorization. Across two-group conditions non
      stereotypic traits were also applied to fewer in-group than out-group members.
      This result suggests that trait favourableness is an important normative
      motivational determinant of perceived homogeneity. A second experiment (N = 297)
      confirmed this point through an additional manipulation of the favourableness of
      checklist traits. This study also replicated the effect for comparative context.
      Implications for the analysis of social categorization, perceived group
      homogeneity and stereotyping are discussed.

PMID- 7620844
TI  - Blood donation and Ajzen's theory of planned behaviour: an examination of
      perceived behavioural control.
AB  - In spite of the success achieved by the theory of reasoned action, researchers
      continue to suggest that new components should be added to the original model.
      Indeed, Ajzen has himself acknowledged that some behaviours may be subject to
      control problems and thus proposed the theory of planned behaviour to handle
      behaviours of this kind. This study set out to explore the predictive superiority
      of the revised theory of planned behaviour by focusing on blood donation, a
      behavioural domain in which volitional control was thought to be incomplete. It
      was also the intention to explore the extent to which the belief-based measure of
      attitude exists as a multidimensional construct. An Ajzen & Fishbein type
      questionnaire was administered to 141 undergraduate students. Multiple regression
      analyses provided strong support for the theory of planned behaviour, suggesting
      that perception of control has an important impact on a person's behavioural
      motivation. Also, some support for a multidimensional representation of the
      belief-based measure of attitude was provided.

PMID- 7620841
TI  - Polymorphic metabolism of flestolol and other ester containing compounds by a
      carboxylesterase in New Zealand white rabbit blood and cornea.
AB  - Flestolol, N(1,1-dimethyl-2-ureidocthyl)-2-hydroxy-3-(o-fluorobenzoyloxy++ +)
      propylamine, (F), is an ester containing an ultra short-acting beta blocker
      intended for the treatment of myocardial dysfunctions. In vitro incubation of F,
      procaine, chloroprocaine, and atropine with blood from different New Zealand
      White (NZW) rabbits resulted in a bimodal distribution (70% fast, 30% slow) of
      ester hydrolysis rates. Using F as a model substrate, bimodal hydrolysis rates
      were also observed in NZW rabbit cornea but not aqueous humor, iris-ciliary body
      complex and ocular tissues of pigmented rabbits. In addition, the bimodal
      distribution of esterase activity was not observed in blood from rats, dogs, and
      humans. Incubation of esters at various positions of the phenoxypropanolamine
      nucleus of beta blockers with NZW rabbit blood indicated structural specificity
      of the carboxylesterase in terms of unimodal or biomodal distribution of
      activity. These results strongly suggest that the carboxylesterase in NZW rabbit
      blood that hydrolyzes F and similar compounds is atropine esterase as described
      in the literature.

PMID- 7620845
TI  - The cognitive organization of sex and occupation stereotypes.
AB  - Two experiments were conducted to explore whether activating occupation
      stereotypes primes sex stereotypes or whether the reverse is more likely. A
      reaction time paradigm was used to distinguish between four alternative
      hypotheses about this issue. More specifically, subjects were exposed to sex
      occupation or occupation-sex word pairs and asked to press one of two buttons
      depending upon their perceptions of the compatibility of the two words. Although
      consistent word pairs were responded to more quickly than inconsistent ones,
      varying the order in which the words were presented (sex first or occupation
      first) did not interact with this factor. This pattern of findings contradicts
      the widely held notion that there is an asymmetrical relationship between the two
      kinds of stereotypes.

PMID- 7620846
TI  - The theory of planned behaviour: the effects of perceived behavioural control and
      self-efficacy.
AB  - The present study was undertaken to assess the utility of the theory of planned
      behaviour, using separate measures of the two variables that are considered to
      comprise the notion of perceived behavioural control, namely, beliefs concerning
      the controllability of the behaviour and efficacy expectancies. The study was
      concerned with the prediction of intentions to engage in regular exercise (for at
      least 20 minutes, three times a week for a fortnight) and actual exercise
      behaviour. A sample of 146 undergraduate subjects participated in the study. It
      was prospective in design; measures of attitudes, norms, intentions, perceived
      control and self-efficacy were obtained at the first wave of data collection,
      while actual behaviour was assessed two weeks later. The results of the study
      revealed support for the view that separate measures of self-efficacy and
      perceived behavioural control should be employed in the theory of planned
      behaviour. In the first instance, confirmatory factor analysis revealed that the
      two variables could be empirically distinguished. Second, the effects of
      perceived behavioural control and self-efficacy on behavioural intentions and
      actual behaviour differed. As predicted, efficacy expectancies influenced
      behavioural intentions, but not actual behaviour. In contrast, levels of
      perceived behavioural control had no effect on behavioural intentions, but
      emerged as a significant (positive) predictor of actual behaviour (there was also
      evidence that the effects of intentions on behaviour were moderated by the level
      of perceived behavioural control).

PMID- 7620847
TI  - Enantioselective determination of chiral 2,2',3,3',4,6'-hexachlorobiphenyl (PCB
      132) in human milk samples by multidimensional gas chromatography/electron
      capture detection and by mass spectrometry.
AB  - The enantiomeric ratio (ER) of the chiral polychlorinated biphenyl (PCB) 132
      (2,2',3,3',4,6'-hexachlorobiphenyl) was determined in human milk samples. The
      enantiomers were separated by multidimensional gas chromatography (MDGC), using
      different achiral columns for pre-separation and a Chirasil-Dex column for
      enantiomer separation, and quantified by electron-capture detection (ECD) and by
      mass spectrometry (MS/SIM). The determined enantiomeric ratios varied between
      0.45-0.85 (enantiomeric excess: 38-8%).

PMID- 7620848
TI  - PCB and organochlorine pesticides in Canadian human milk--1992.
AB  - Human milk (497 samples) representing donors from across Canada were analyzed for
      24 organochlorine pesticides and industrial chemicals and 40 PCB congeners. PCBs,
      p,p'-DDE, hexachlorobenzene (HCB), and trans nonachlor were present in all
      samples. Compared to earlier surveys in Canada, concentrations of most residues
      determined declined, and were lower than those reported recently in European
      countries. Although regional differences were minor, residues of PCBs, p,p'-DDE,
      and trans nonachlor were higher in the Ontario, Quebec, and Eastern regions, and
      all residues were slightly higher in the Great Lakes Basin compared to the rest
      of Canada. Concentrations of PCBs, DDTs, HCB, and trans nonachlor were higher in
      participants who consumed greater than 100 g of fish weekly.

PMID- 7620849
TI  - Biodegradation of toluene diamine (TDA) in activated sludge acclimated with
      aniline and TDA.
AB  - The biodegradability of toluene diamine (TDA) which has been regarded as a
      "recalcitrant compound" was examined in activated sludges. In this study, a
      microorganic-enzyme system which metabolized TDA was obtained by acclimating the
      activated sludge with aniline and TDA. In the sludge subject to be 200 days'
      acclimation, the considerable increase in respiration rate with the addition of
      TDA, accompanied the sharp decrease in its concentration. This indicated that TDA
      was metabolized fortuitously. The rate of biodegradation of TDA in the absence of
      aniline was first order with respect to its concentration when the initial TDA
      concentration was less than about 5 mg/l. The rate constant in this relation was
      proportional to mixed liquor suspended solid (MLSS). However, when the initial
      TDA concentration exceeded 5 mg/l, the plots were deviated from a first order
      rate equation.

PMID- 7620850
TI  - The determination of strong mutagen MX [3-chloro-4-(dichloromethyl)-5-hydroxy
      2(5H)-furanone] in drinking water in China.
AB  - The strong mutagen, [3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone] (MX)
      was found to occur in chlorinated drinking water in China. Some tap water samples
      from Jiangsu province, which contained MX of 3-60ng/L, were analyzed.
      Quantitation is based on gas chromatography-mass spectrometry, using peak area of
      selective ion monitoring of the methyl derivative of MX.

PMID- 7620852
TI  - Absorption of polychlorinated biphenyls, dibenzo-p-dioxins and dibenzofurans by
      breast-fed infants.
AB  - The absorption of polychlorinated biphenyls, dibenzo-p-dioxins and dibenzofurans
      was studied in four breast-fed infants. The absorption was measured by comparing
      the estimated total intake and the excretion in faeces, during 48 hours, at three
      different time points; 1, 2 and 3 months post parta. The levels of the analysed
      compounds in the human milk are typical for Sweden, i.e approximately 20 ppt
      toxic equivalents for the dibenzo-p-dioxins and dibenzofurans and for the
      polychlorinated biphenyls approximately 16 ppt toxic equivalents. For most of the
      congeners the absorption is found to be over 95%. Higher excretion is noticed for
      heptachlorinated and octachlorinated dioxins.

PMID- 7620853
TI  - Glomerular remodelling after inflammatory injury.

PMID- 7620851
TI  - Exposure analysis of the inhabitants living in the neighbourhood of a mercury
      contaminated industrial site.
AB  - The inhabitants living in the neighbourhood of a deserted mercury-contaminated
      industrial site are subjected to an age-group differentiated mercury exposure
      assessment based on a scenario-linked calculation. Analytical input data for the
      calculation procedure are provided for from soil, air and plants in a large
      number. The most sensitive group are small children being mainly exposed by soil
      ingestion which makes up nearly 80% of the ADI, followed by inhalation of mercury
      contaminated indoor air. On the other hand, inhalation of indoor air has a
      predominant impact on youth and adults.

PMID- 7620854
TI  - Kid-1, a kidney transcription factor.

PMID- 7620855
TI  - Localization of PDGF-BB in the juxtaglomerular cells of cyclosporin-treated rats.
AB  - We have examined the ultrastructural localization of immunoreactive platelet
      derived growth factor (PDGF) in Wistar rats injected with cyclosporin A (CyA,
      12.5 mg/kg/day) for 4 weeks. CyA injections resulted in a significant increase in
      serum creatinine (47 +/- 3 vs. 35 +/- 2 mumol/l, p < 0.05) and a reduction in
      creatinine clearance (0.29 +/- 0.07 vs. 0.53 +/- 0.04 ml/min/100 g b.w., p <
      0.01). CyA-treated rats displayed marked hypertrophy and hypergranularity of the
      juxtaglomerular cells. Morphometric studies showed a significant increase in the
      number (2.8 +/- 0.3 vs. 1.8 +/- 0.3, p < 0.05) and a 60% increase in the volume
      of secretion granules within these cells. PDGF was detected exclusively within
      the secretion granules of the juxtaglomerular cells of the afferent arterioles of
      CyA-treated animals. We conclude that CyA therapy or its induced haemodynamic
      alterations result in increased accumulation of PDGF-BB within the secretion
      granules of the juxtaglomerular cells.

PMID- 7620856
TI  - Effects of inhibition of the vacuolar-type proton pump on nephron ultrastructure
      and acidification in the isolated perfused rat kidney.
AB  - The effects of bafilomycin, an inhibitor of the vacuolar-type (V-type) proton
      pump, on nephron ultrastructure and acidification were analyzed in isolated
      perfused kidneys from rats with acute metabolic acidosis. Acidic intracellular
      compartments were labelled with the weak base DAMP, that was subsequently
      visualized immunocytochemically. The distribution of the proton pump was studied
      by immunocytochemistry. Bafilomycin inhibited urinary acidification and caused
      pronounced ultrastructural changes in proximal tubule cells and B-type
      intercalated cells (B-IC cells). Immunoreactivity for DAMP showed that
      bafilomycin also inhibits intracellular acidification. The distribution of the
      proton pump was essentially unchanged by bafilomycin in A-IC cells. In B-IC
      cells, immunoreactivity accumulated over studded membrane material in the apical
      cytoplasm. The results indicate that the V-type proton pump is important both for
      intracellular and for urinary acidification.

PMID- 7620857
TI  - Effect of intracellular unstirred layer on apparent reflection coefficient for
      urea in inner medullary collecting duct: a computer simulation.
AB  - In the vasopressin-stimulated inner medullary collecting duct (IMCD), urea is
      transported through a pathway which is distinct from a water channel. Therefore,
      no frictional interaction between urea and water should occur at the membrane
      level, and the reflection coefficient for urea must be close to unity. However,
      the presence of unstirred layers in the vicinity of membranes causes solute
      concentration polarization, leading to an underestimation of the reflection
      coefficient (apparent reflection coefficient). When the value is determined
      across the perfused renal tubular wall, the intracellular space also constitutes
      an unstirred layer. The profile of solute and water transport across the system
      consisting of two membranes and the interposed intracellular space was simulated
      by a computer to examine the effect of unstirred layer on the value of apparent
      reflection coefficient. The model demonstrated that the imposed osmotic gradient
      across the tubular epithelial is decreased at each membrane interface. Under
      conditions of minimal unstirred layers in the bathing fluid, the existence of the
      intracellular constraints to diffusion cause considerable underestimation of the
      reflection coefficient. The higher the membrane permeability of urea and the
      smaller the diffusion coefficient of urea in the intracellular space, the greater
      becomes the magnitude of the underestimation. Thus, the measured apparent
      reflection coefficient for urea may become significantly less than the estimated
      value, leading to a reduction of the effective transmural osmotic driving force.

PMID- 7620858
TI  - On misrepresenting one's credentials.

PMID- 7620859
TI  - Diagnosing deep vein thrombosis in elderly hip fractures.

PMID- 7620860
TI  - Synovial chondromatosis of the biceps tendon sheath.

PMID- 7620861
TI  - Highlights of talipes equinovarus deformity.
AB  - Talipes equinovarus deformity has been extensively reported; however, controversy
      still exists regarding the cause, mechanism of the deformity, and treatment. This
      paper highlights these controversies to enhance understanding of this deformity.

PMID- 7620862
TI  - Painful basal joint arthritis of the thumb. Part I: Anatomy, pathophysiology, and
      diagnosis.
AB  - Pathology at the base of the thumb can often be confusing. Numerous tendons,
      nerves, bones, and joints are all in close proximity and may cause pain and loss
      of function to the thumb. A systematic approach to this area, identifying
      abnormal anatomy or lesions of these structures, is presented along with the
      characteristic features of the examination of the pathologic basal joint. The
      importance of obtaining a careful medical history with regard to possible causes
      and symptoms is presented. Concurrent conditions, which are present in a large
      percentage of patients, are discussed. Radiographic views for diagnosis and
      staging will be demonstrated.

PMID- 7620863
TI  - Evaluation of the anatomic patellar prosthesis in uncemented porous-coated total
      knee arthroplasty: seven-year results.
AB  - We studied 41 patients (56 knees; mean patient age, 55.3 years) who were followed
      up for a minimum of 7 years (range, 84 to 90 months) after primary resurfacing
      arthroplasty of the patella with an anatomic patellar prosthesis during
      uncemented porous-coated anatomic total knee arthroplasty. The operative
      diagnosis was osteoarthritis in 33 knees; rheumatoid arthritis in 16; tuberculous
      arthritis in 4; posttraumatic arthritis in 2; and ankylosis in 1. The average
      preoperative Hospital for Special Surgery knee score was 33 points (range, 10 to
      69 points), which improved to 81 points (range, 54 to 100 points) at the final
      follow-up examination. There was a high rate of component loosening (23 knees or
      41%). A total of 27 of 33 solidly fixed patellar prostheses (82%) had osteolysis
      in the patella. Forty-two knees (75%) had wear of the tibial polyethylene liners;
      a mean of 2.5 mm in the medial compartment and 1.7 mm in the lateral compartment.
      Our experience does not support the continued use of this prosthesis.

PMID- 7620864
TI  - Transpedicular drainage of Pott's abscess. A report of two cases.
AB  - The treatment of Pott's disease remains controversial. The authors present two
      cases of spinal tuberculosis treated with posterior stabilization and
      supplementary abscess evacuation via the pedicular route with subsequent
      chemotherapy. The aim of this procedure was to increase the healing rate.
      Radiographic evidence of bone healing without any sequelae was demonstrated at 13
      and 14 months.

PMID- 7620865
TI  - Cogan's syndrome mimicking acute Lyme arthritis.
AB  - A pediatric case of Cogan's syndrome mimicking acute Lyme arthritis is described.
      A 12-year-old black boy was admitted to the pediatric service for presumed right
      knee septic arthritis. Symptoms included acute pain and swelling with decreased
      range-of-motion. Although the patient's right knee symptoms and positive Lyme
      serology were consistent with a diagnosis of Lyme arthritis, the presence of
      sensorineural hearing loss and interstitial keratitis with inflammatory arthritis
      suggested a diagnosis of Cogan's syndrome. Subsequent Western blot analysis was
      negative for Borrelia burgdorferi antigens. The patient had dramatic clinical
      improvement of musculoskeletal and ophthalmologic complaints shortly after
      receiving high-dose corticosteroids, although residual sensorineural hearing loss
      persisted.

PMID- 7620866
TI  - Giant synovial cyst of the shoulder presenting as a chest wall mass.
AB  - Synovial cysts are most frequently found about the knee. Less commonly they have
      been described at the shoulder, elbow, ankle, and hip joints. Synovial cysts of
      the shoulder are associated with rheumatoid arthritis, osteoarthritis, chronic
      steroid use, Charcot joint disease, and long-standing rotator cuff tears.
      Although often asymptomatic, patients may present complaining of pain, loss of
      joint motion, or presence of an unexplained mass. The authors present the case of
      an elderly man with a very large synovial cyst presenting as an anterior chest
      wall mass.

PMID- 7620867
TI  - A 13-year-old boy with rapidly progressive spinal deformity.
AB  - The following case is presented to illustrate the roentgenographic and clinical
      findings of a condition of interest to the orthopedic surgeon. Initial history,
      physical findings, and roentgenographic examinations are found on the first page.
      The final clinical and roentgenographic differential diagnoses are presented on
      the following pages.

PMID- 7620868
TI  - Intraoperative hand retractor.
AB  - A technique is described that greatly reduces the problems inherent in obtaining
      clear radiographs of the fingers. The method is simple, inexpensive, and readily
      available for use in the operating room. Additionally, it allows the surgeon to
      leave the operative field and stand behind a lead shield while radiographs are
      taken.

PMID- 7620869
TI  - Beating the competition: the reliability hypothesis for Mauthner axon size.
AB  - The Mauthner cell has an axon that is among the largest in diameter of any
      vertebrate neuron. It is commonly thought that the large size is needed for short
      latency escape responses involving a major contraction of the trunk musculature.
      Previous work, however, has shown that there is nothing unique about the strength
      of the Mauthner initiated response, compared to responses initiated by other
      smaller cells, and it is debatable that there is any important improvement in
      response latency due to Mauthner axon size. In this paper we advance an
      alternative explanation: although the Mauthner cell has a powerful excitatory
      influence on motoneurons, the large size of the Mauthner axon is most important
      in rapidly spreading an inhibitory signal that turns off other competing motor
      commands. Such competing commands are likely to arise in the presence of ongoing
      swimming behavior or ambiguous stimuli that could activate a fast turn either
      toward or away from the stimulus. These stimuli include apparent food items, or
      lures, presented by predators (such as anglerfish) and escape eliciting sounds
      which, in the presence of background noise, may have 180 degrees directional
      ambiguity. Thus, large size of the axon contributes most to the reliable
      expression of the escape behavior. We base this reliability hypothesis on a
      retrospective analysis of previous neurophysiological data and new anatomical
      measurements of the diameters of the large spinal cord axons from which we
      calculated conduction velocities. Our calculations show that the Mauthner-derived
      inhibition is fast enough that it allows an escape response to occur even when a
      conflicting motor command enters the spinal cord at the same time as the Mauthner
      axon impulse. The rapid spread of inhibitory influence, along with excitation,
      may be a general feature of motor system cells with large axonal diameters.

PMID- 7620870
TI  - Connections of the posterior pallium in the crested newt, Triturus carnifex.
AB  - The connections of the posterior pallial regions were studied in the crested
      newt, Triturus carnifex, by means of the horseradish peroxidase technique. The
      tracer was injected into the lateral and medial pallia, caudal to the
      interventricular foramen. In addition, the connections between the posterior
      pallium and the infundibular hypothalamus were investigated with both horseradish
      peroxidase and the fluorescent dye DiI. The results show important differences
      between the connection patterns of the medial and lateral pallia. The lateral
      pallium receives inputs from the main olfactory bulb and send fibers to the
      contralateral hemisphere through the anterior commissure. It also shows modes
      extra-telencephalic connections. Conversely, the medial pallium receives direct
      afferent inputs from the amygdala (pars medialis) and the anterior dorsal
      thalamus. It is reciprocally connected to the contralateral homologue region
      through the hippocampal commissure, and its main efferent system is the medial
      forebrain bundle, which reaches the infundibular hypothalamus. The infundibulum
      also receives a prominent projection from the amygdala (pars lateralis). The
      connectivity of the posterior pallium is comparable to that reported previously
      for the anterior pallium, although a few differences are noted. These differences
      in the connectivity of the lateral pallium and the medial pallium may reflect
      different functional properties of these telencephalic regions.

PMID- 7620871
TI  - The orientation of the cervical vertebral column in unrestrained awake animals.
      II. Movement strategies.
AB  - Previously we demonstrated a stereotyped resting posture of the head-neck
      arrangement in a number of vertebrates: the cervical vertebral column is oriented
      vertically to form one portion of the partial S-shaped configuration of the
      entire spine. The present investigation quantified the various strategies of head
      neck movements employed by different mammalian species (human, monkeys, cats,
      rabbits and guinea pigs) using cineradiography. At rest, bipeds and quadrupeds
      hold their heads at the extreme point of flexion of the passive atlanto-occipital
      range of motion. In this posture, the horizontal semicircular canals are tilted
      upward from earth horizontal by 5 to 10 degrees and roughly parallel the plane
      determined by the two obliquus capitis posterior muscles. Furthermore, at this
      head position, the utricular maculae become oriented earth-horizontally. In
      quadrupedal animals, head-neck movements in the sagittal plane result from
      movement at the atlanto-occipital articulation (head/C1) and at the multi
      articular cervico-thoracic junction (C6-Th3). Only very small flexion/extension
      movements occur within the body of the cervical vertebral column (C2-C5).
      Lowering the head from the resting position is only possible by flexion at the C6
      Th3 vertebrae. Raising of gaze from the resting position is only possible by
      extension of the head at the atlanto-occipital articulation. By contrast,
      sagittal plane head movements in bipeds are largely confined to the cervico
      thoracic junction. This is related to a significantly reduced range of motion of
      the atlanto-occipital articulation. In monkeys and humans, it range of motion is
      about 13 and 8-11 degrees, respectively, compared to 105 degrees in rabbits. Our
      cineradiographic data demonstrated different strategies for head movements in the
      sagittal plane between quadrupeds and bipeds. At one end of the spectrum, in the
      case of rabbits, there was no systematic relationship between head and neck
      orientation. Rabbits stabilized head posture by using the head-neck structure in
      a parallelogram fashion, which resulted in head posture being largely independent
      of cervical vertebral column orientation. In monkeys and humans, however,
      orientation of the head depended almost entirely on the orientation of the
      cervical vertebral column. In such case, head movements in the sagittal plane
      almost exclusively relied on the positioning of the cervico-thoracic junction.
      These different strategies again correlate with the different ranges of motion of
      the atlanto-occipital articulation. We suggest that vertebrates use mechanical
      constraints and preferred planes of action for head-neck movement control to
      simplify sensory-motor transformations subserving motor control and plasticity
      and to minimize neuronal operations.

PMID- 7620872
TI  - Interspecific variation of photoreceptors in four co-existing haplochromine
      cichlid fishes.
AB  - The photoreceptors of four co-existing haplochromine cichlids have been studied
      morphometrically and microspectrophotometrically, and the results were
      interpreted in terms of resolution and sensitivity. Among the three species,
      Haplochromis argens, H. piceatus and H. ishmaeli, the cone dimensions and the
      visual pigments differed only slightly, in spite of differences in vertical
      distribution and feeding behaviour between these species. The fourth species H.
      pyrrhocephalus showed distinctly different visual properties, with very large
      double cones at low densities, and its spectral sensitivity shifted to
      significantly longer wavelengths. To some degree, the photoreceptor morphometrics
      and visual pigments appeared to be attuned to the photic conditions of the
      specific habitats. The two species H. piceatus and H. pyrrhocephalus, occupying a
      dimmer habitat with less penetrating blue light, had reduced blue sensitive
      single cones, whereas the surface dwelling species H. argens had relatively small
      red/green sensitive double cones. Also an attempt has been made to relate the
      visual capacity of the cichlids to their behavioural patterns, focussing on prey
      detection. The greatest visual differences were observed in the two species H.
      argens and H. pyrrhocephalus, with resources coincidence and with the highest
      encounter frequency, which may indicate that visual segregation contributes
      towards reducing interference competition among co-existing species with a
      similar diet.

PMID- 7620873
TI  - Comparative distribution of 2[125I]iodomelatonin binding in the brains of diurnal
      birds: outgroup analysis with turtles.
AB  - The roles that the pineal gland and its hormone melatonin play in the regulation
      of circadian rhythmicity and photoperiodism vary among vertebrate species.
      Recently, putative sites of melatonin action have been elucidated in several
      avian and mammalian species by application of in vitro binding of a
      radioiodinated melatonin agonist, 2[125I]iodomelatonin (IMEL) and
      autoradioradiography. These studies in mammals, birds and reptiles have indicated
      profound differences in the distribution of IMEL binding between these diverse
      groups, suggesting that these large differences in binding may reflect
      differences in melatonin function. The present study was performed to determine
      systematically whether the variance in IMEL binding among avian species
      corresponds to changes in circadian organization and/or phylogenetic
      relationships. The distribution of specific IMEL binding was determined in the
      brains from birds belonging to 14 different species in 5 Orders (Psittaciformes,
      Passeriformes, Columbiformes, Galliformes and Anseriformes) using in vitro
      binding, autoradiography and computer-assisted image analysis. The distribution
      was compared to a similar study in 3 species of turtles as an outgroup. The data
      indicated IMEL binding in retinorecipient structures of the circadian,
      tectofugal, thalamofugal and accessory optic visual pathways in all avian
      species. Relay nuclei and integrative structures of the tectofugal, thalamofugal,
      accessory optic, and limbic systems, however, bound the hormone to varying
      degrees. In turtles, binding was observed in retinorecipient structures of the
      thalamofugal visual pathway and in retinorecipient and integrative areas of the
      tectofugal visual pathway. No binding was observed in the pineal gland, tuberal
      hypothalamus or adenohypophysis in any avian or testudine species. This
      distribution is drastically different from that observed in mammals, where
      binding predominates in the pars tuberalis of the adenohypophysis and in the
      suprachiasmatic nucleus, suggesting that the circadian system may influence a
      wide array of sensory and integrative functions in birds and reptiles through the
      circadian secretion of melatonin, but that this capacity has been lost in
      mammals.

PMID- 7620874
TI  - Ganglion cell topography of the retina in the bottlenosed dolphin, Tursiops
      truncatus.
AB  - The distribution and size of ganglion cells in the retina of the bottlenosed
      dolphin are described. Ganglion cells concentrate at two spots of the highest
      density in the nasal and temporal quadrants, 15 to 16 mm (50 to 55 degrees) from
      the optic disk. The mean peak cell density in both spots is about 670 cells/mm2.
      With a posterior nodal distance of 14.5 mm (under water), this corresponds to 43
      cells/deg2, which provides a retinal resolution of about 9' in water and 12' in
      air. Mean cell size was from 26 to 31 microns in various parts of the retina.

PMID- 7620875
TI  - Vestibular compensation in the European green frog (Rana esculenta L.) and effect
      of training on compensation.
AB  - Compensation of the vestibular deficits following section of the ampullary nerve
      of a horizontal semicircular canal was studied from a behavioral point of view in
      the European green frog. Post-rotation reactions, which are highly asymmetrical
      the day after the lesion, become symmetrical, as they are in intact animals, 45
      60 days later. It was shown that vestibular and motor training given
      postoperatively did not enhance the rate at which compensation was achieved.

PMID- 7620876
TI  - Distribution of neurons projecting to the trochlear nucleus in goldfish
      (Carassius auratus).
AB  - The distribution of neurons projecting to the trochlear nucleus of goldfish
      (Carassius auratus) was studied by the electrophoretic injection of horseradish
      peroxidase into the nucleus. The location of the injection site was
      electrophysiologically determined by the antidromic field potential elicited from
      the trochlear nucleus after the electrical stimulation of its nerve. Retrogradely
      labeled neurons were observed in the following structures: (1) anterior,
      tangential and descending nuclei of the octaval column--afferents to these nuclei
      were mainly ipsilateral for the former and exclusively contralateral for the
      other two; (2) cerebellum; (3) rhombencephalic reticular formation, near the
      abducens nucleus; and (4) nucleus of the medial longitudinal fasciculus. In
      addition, a few stained neurons were scattered in the nucleus of the posterior
      commissure and in nucleus pretectalis superficialis pars magnocellularis. These
      results are compared with the afferent sources to trochlear nucleus in mammals
      and with the set of structures projecting to the oculomotor and abducens nuclei
      in goldfish. It is suggested that the neuronal pathways involved in the
      compensatory vestibular and optokinetic reflexes, as well as in the saccadic
      system, are similarly organized in vertebrates but that the relative importance
      of some of the components of these pathways varies.

PMID- 7620877
TI  - Domestication and plasticity of brain organization in mallards (Anas
      platyrhynchos).
AB  - The sizes and histological differentiation of structures in the central nervous
      system of wild and domestic ducks were compared using allometric methods. Whole
      brain volume is 14.3% less in domestic ducks than in wild birds, and the size of
      certain brain structures is more variable in domestic ducks than in the wild
      birds. These findings are consistent with results of studies in other domestic
      birds and in domestic mammals. Although the brain subdivision volumes are not
      reduced to the same extent, the relative composition of the brain is maintained
      in domestic ducks. The overall reduction in rhombencephalic parts of the brain
      (16.3%) is greater than that in the prosencephalon (13.5%). Within sensory
      centers the nuclei of the trigeminal system undergo the most marked decrease
      (21.3%). Optic (13.3%) and limbic (11.1%) structures are less reduced, and the
      olfactory regions do not show any differences in volume compared to these regions
      in wild mallards. Reductions in the volumes of brain structures in domesticated
      animals have been thought to be processes of functional adaptation controlled by
      artificial selection. Our observations are discussed with regard to hypotheses
      about trends in domestication and evolutionary plasticity.

PMID- 7620878
TI  - Avian neurosteroids. I. Pregnenolone biosynthesis in the quail brain.
AB  - The present study was carried out to determine steroid biosynthesis from
      cholesterol in the brain of adult male Japanese quails. As an initial step of the
      experiments, the concentrations of pregnenolone, dehydroepiandrosterone and their
      sulfate esters in the brain and plasma extracts were measured by specific
      radioimmunoassays (RIAs). To exclude the possibility that these steroids in the
      brain are derived from peripheral steroidogenic glands, hypophysectomized and
      sham-operated birds were used in this experiment. The pregnenolone concentration
      was much larger in the brain than in the plasma in these two groups.
      Hypophysectomy led to decreases in the plasma and brain pregnenolone
      concentrations, but the change in the brain was less pronounced than that in the
      plasma. Although pregnenolone sulfate ester, dehydroepiandrosterone and its
      sulfate ester were also detected in brain extracts, those levels were low in both
      hypophysectomized and sham-operated birds. The biochemical demonstration of
      cholesterol metabolism was further conducted in intact mitochondria. When
      mitochondrial fractions obtained from the whole brain were incubated with
      cholesterol at 37 degrees C, the pregnenolone level in mitochondria increased as
      a function of incubation time. Finally, Western immunoblot analysis using a
      purified IgG with polyclonal antibodies against the purified bovine adrenal
      cytochrome P450scc was performed after SDS-gel electrophoresis of homogenates of
      the hypothalamus and preoptic area. A protein recognized the antibody as a band
      of electrophoretic mobility in the proximity of reference bovine P450scc. These
      results suggest that the brain produces pregnenolone from cholesterol in adult
      male Japanese quails. Most accumulation of pregnenolone in the brain may be
      independent of the peripheral endocrine gland system.

PMID- 7620879
TI  - Avian neurosteroids. II. Localization of a cytochrome P450scc-like substance in
      the quail brain.
AB  - We have recently demonstrated that the avian brain as well as the peripheral
      steroidogenic glands produces pregnenolone, the main precursor of steroid
      hormones, on the basis of biochemical studies. Therefore, the immunohistochemical
      and Western immunoblotting analyses with a polyclonal antibody directed against
      the purified bovine adrenal cytochrome P450scc, which is involved in pregnenolone
      formation, was undertaken to investigate the localization of a cytochrome P450scc
      like substance in the brain of adult male Japanese quails. P450scc-like
      immunoreactive cells were distributed in several telencephalic, diencephalic and
      mesencephalic regions. An intense immunoreaction was observed in somata of
      Purkinje cells and in the dendrites extending through the cerebellar molecular
      layer. Clusters of immunoreactive cell bodies were also detected in the
      hyperstriatum accessorium (HA), the ventral portions of both the archistriatum
      and the corticoid area, the preoptic area (POA), the anterior hypothalamus (AHy)
      and the dorsolateral thalamus (DL). Preadsorbing the antibody with cytochrome
      P450scc resulted in a complete absence of P450scc-like immunoreactivity in all of
      positively stained cells. On Western immunoblotting with the P450scc antibody, a
      P450scc-like substance was present in homogenates of the several brain regions
      that contain immunohistochemically stained cells. Immunohistochemical experiments
      using both antibodies against P450scc and the glial fibrillary acidic protein
      (GFA), a specific marker of glial cells, indicated that many HA cells contained
      both P450scc-like and GFA-like immunoreactivities. However, no immunoreactivity
      for GFA was observed in Purkinje cells and the cells localized in the ventral
      portion of the corticoid area, despite the presence of P450scc-like
      immunoreactivity. These results confirm our previous findings of pregnenolone
      biosynthesis and suggest the presence of a P450scc-like substance in both
      neuronal and glial cells of the quail brain.

PMID- 7620880
TI  - 2,3-Butanedione monoxime protects mice against the convulsant effect of
      picrotoxin by facilitating GABA-activated currents.
AB  - While adult mice receiving picrotoxin (PTX) alone responded with clonic and tonic
      clonic seizures, this response was greatly suppressed for mice simultaneously
      injected with 2,3-butanedione monoxime (BDM). For example, 60% and 10% of the
      mice convulsed when injected (i.p.) with 3.0 mg/kg PTX alone or PTX plus 205
      mg/kg of BDM, respectively. In contrast, a non-oxime analogue of BDM, 2,3
      butanedione (BTD), did not have this anticonvulsant effect. In order to explore
      the basis for the anticonvulsant effect of BDM, we recorded GABA-activated
      currents (IGABA) of frontal cortical as well as ventromedial hypothalamic neurons
      before, during and after exposure to this oxime. BDM had a biphasic effect on
      IGABA. That is, high concentrations (100 microM-40 mM) decreased and lower
      concentrations (0.01 microM-0.001 microM) potentiated IGABA; these effects of BDM
      reversed upon washout of the oxime. In contrast, BTD had no effect on IGABA.
      Finally, when 0.001 microM BDM, 10-30 microM PTX and GABA were co-applied the
      inhibitory effect of the toxin on IGABA was markedly suppressed. These data
      suggest that the anticonvulsant effect of oximes involves facilitation of the
      inhibitory action of GABA.

PMID- 7620881
TI  - Theta-like rhythm in depth EEG activity of hypothalamic areas during spontaneous
      or electrically induced locomotion in the rat.
AB  - Spontaneous locomotion performed by an awake rat is accompanied by synchronized
      activity (a theta rhythm) of the hippocampus (Hipp). Locomotion can also be
      induced by electrical stimulation of various sites within the brain. The
      effectiveness of electrical stimulation of the subthalamic locomotor region (SLR)
      and posterior hypothalamus (PH) in inducing locomotor movements has previously
      shown that they are parts of the system controlling locomotion. Thus, it was of
      interest to determine whether their electrical activity was correlated with the
      motor behavior, as it is in the Hipp. The experiments done here on chronic
      animals with electrodes implanted into the Hipp and hypothalamus showed that
      rhythmic depth EEG activity (theta-like) similar to that found in the Hipp is
      present in motor-positive hypothalamic areas during spontaneous locomotion. In
      addition, our results showed that movements induced by stimulation of various
      hypothalamic sites are also accompanied by theta-like activity in the Hipp and
      some hypothalamic areas. Thus, our results support the idea that the well-known
      and anatomically established connections between the Hipp and hypothalamus are
      active during locomotion. These connections may constitute a part of the system
      involved in the control of the motor behavior.

PMID- 7620882
TI  - Fos induction in the medullary dorsal horn and C1 segment of the spinal cord by
      acute inflammation in aged rats.
AB  - In order to elucidate the effect of aging on nociceptive neurons in the central
      nervous system, c-fos was used as a marker of excitability of neurons in the
      medullary dorsal horn (MDH) and the first spinal segment (C1) following noxious
      stimulation of the lateral face of young and aged rats. The distribution of c-fos
      positive cells was dense in the superficial laminae and sparse in the deep
      laminae of the MDH and C1 in both young and aged animals following subcutaneous
      injection of formalin into the lateral face, whereas few c-fos-positive cells
      were labeled after saline injection. The distribution of c-fos-positive cells in
      the superficial laminae of the aged rats was found to be denser and more rostro
      caudally expanded compared to that in the young rats. C-fos-positive cells were
      distributed more rostro-caudally in aged than in young rats. There was no
      difference between young and aged rats in the distribution of c-fos-positive
      cells in the deep laminae. Substance P (SP), 5-HT and calcitonin gene-related
      peptide-like immunoreactive (CGRP-LI) fibers and varicosities showed similar
      distribution density in the MDH and C1. Furthermore, many 5-HT-LI aberrant fibers
      and varicosities were observed in the MDH and C1 of the aged rats. The SP-LI and
      CGRP-LI cells in the trigeminal ganglion of aged rats were larger than those of
      young rats. These findings suggest that a deficit of the descending 5-HT
      inhibitory system produces the increment of c-fos-positive cells in the MDH and
      C1 of aged rats, resulting in the recruitment of a larger number of neurons in
      the superficial laminae of the MDH and C1 for conveying nociceptive sensory
      information to the central nervous system.

PMID- 7620883
TI  - Properties of peripherally induced persistent hindlimb flexion in rat:
      involvement of N-methyl-D-aspartate receptors and capsaicin-sensitive afferents.
AB  - In the sodium pentobarbital anesthetized rat, percutaneous electrical stimulation
      (2 mA, 7 ms, 100 Hz, 60 min) across the upper hindlimb produces an ipsilateral
      hindlimb flexion that persists following spinal transection. Using this
      preparation, the following were found. (1) Flexion was observed in both the
      intact and acutely spinalized (T7) rat 10 hours to two weeks following induction,
      but was negligible at six weeks. (2) Pretreatment of intact rats with the non
      competitive N-methyl-D-aspartate (NMDA) receptor antagonists, ketamine HCl and MK
      801, reduced persistent hindlimb flexion in a dose-dependent manner. (3)
      Pretreatment of spinalized rats with MK-801 reduced the amount of flexion,
      observed at 30 min following stimulation. However at 72 hrs following
      stimulation, administration of MK-801 to acutely spinalized rats had no effect on
      flexion. (4) Capsaicin pretreatment, of either neonates or adults, reduced the
      amount of flexion observed at 30 min following stimulation, but only adult
      capsaicin pretreatment reduced flexion at 72 h. (5) At 72 h following induction,
      bilateral dorsal rhizotomy (T11-L6) of acutely spinalized rats had no significant
      effect on flexion when compared to pre-rhizotomy levels. However, the subsequent
      removal of the hindlimb skin produced a significant reduction in flexion, and the
      remaining flexion was eliminated by the removal of the thoracolumbar spinal cord
      and cauda equina. These combined results suggest that prolonged activation of C
      afferents and NMDA receptors induce a persistent hindlimb flexion in rat that is
      maintained at the level of the spinal cord.

PMID- 7620884
TI  - Temporal response and effects of excitatory amino acid antagonism on microtubule
      associated protein 2 immunoreactivity following experimental brain injury in
      rats.
AB  - Alterations in microtubule-associated protein 2 (MAP2) immunoreactivity following
      lateral fluid-percussion (FP) brain injury were investigated in rats with
      survival times ranging between 10 min and 7 days. MAP2 immunoreactivity was
      profoundly diminished in the cortex and hippocampus ipsilateral to the site of
      injury by 10 min and remained diminished up to 7 days after injury. Nissl
      staining and silver impregnation histochemistry demonstrated a correlation
      between the loss of MAP2 and neuronal degeneration. The effect of excitatory
      amino acid receptor antagonism on MAP2 immunoreactivity was evaluated by
      administering kynurenate or buffer 15 min after FP injury. Administration of
      kynurenate significantly attenuated the loss of MAP2 observed in the cortex two
      weeks after injury when compared to buffer treated control animals (P < 0.02). We
      conclude that significant and prolonged cytoskeletal changes occur following
      lateral FP brain injury, and that these alterations can be attenuated by blocking
      excitatory amino acid receptors.

PMID- 7620885
TI  - Reductions in body weight following chronic central opioid receptor subtype
      antagonists during development of dietary obesity in rats.
AB  - Acute administration of long-acting general opioid antagonists reduces body
      weight and food intake in rats. In contrast, chronic administration of short
      acting general opioid antagonists produces transient effects. The present study
      evaluated whether chronic central administration of selective long-acting
      antagonists of mu (beta-funaltrexamine, BFNA, 20 micrograms), mu1 (naloxonazine,
      50 micrograms), delta1 ([D-Ala2,Leu5,Cys6]-enkephalin, DALCE, 40 micrograms),
      delta2 (naltrindole isothiocyanate, NTII, 20 micrograms) or kappa (nor
      binaltorphamine, NBNI, 20 micrograms) opioid receptor subtypes altered weight and
      intake of rats exposed to a palatable diet of pellets, fat, milk and water,
      relative to pellet-fed and diet-fed controls. Diet-fed rats receiving chronic
      vehicle injections significantly increased weight (7-10%) and intake over the 11
      day time course. Weight was significantly reduced over the time course in rats
      administered either BFNA (9%), naloxonazine (12%), DALCE (7%) or NTII (6%).
      Initial weight reductions failed to persist following chronic NBNI. All
      antagonists chronically reduced fat intake, but did not systematically alter
      total intake, pellet intake or milk intake relative to the pattern of weight
      loss. These data indicate that central mu, mu1, delta1, delta2, and, to a lesser
      degree, kappa receptors mediate long-term opioid modulation of weight even in
      animals maintained on diets that ultimately result in dietary obesity.

PMID- 7620887
TI  - The action of 5-HT on calcium-dependent potassium channels and on the spinal
      locomotor network in lamprey is mediated by 5-HT1A-like receptors.
AB  - 5-HT has a powerful modulatory action on the firing properties of single neurons
      as well as on locomotor activity. In lamprey, 5-HT increases the neuronal firing
      frequency in spinal neurons by reducing the conductance in Ca(2+)-dependent K+
      channels (KCa) underlying the slow afterhyperpolarization (sAHP), and it also
      lowers the burst frequency of the spinal locomotor network. To elucidate which
      type of 5-HT receptor mediates these effects, different specific receptor
      agonists and antagonists were applied during intracellular current clamp
      recordings and during NMDA-induced fictive locomotion in the lamprey spinal cord
      in vitro preparation. The 5-HT1A receptor agonist 8-OH-DPAT ((+/-)-8-hydroxy
      dipropylaminotetralin hydrobromide), the 5-HT1 receptor agonist 5-CT (5
      carboxyamidotryptamine maleate) and the 5-HT2 receptor agonist alpha-CH3-5-HT
      (alpha-methylserotonin maleate) all reproduced the actions of 5-HT at both the
      cellular and the network levels. The effects of all agonists were completely or
      partially blocked by the 5-HT1A and 5-HT2 receptor antagonist spiperone
      (spiroperidol hydrochloride) while selective 5-HT2 receptor antagonists were
      ineffective. The selective 5-HT1A receptor antagonist S(-)-UH301 (S(-)-5-fluoro-8
      hydroxy-dipropylaminotetralin hydrochloride) also counteracted the effect of 5-HT
      on the sAHP. 5-HT3 and 5-HT4 receptor agonists and antagonists were without
      effects. The intracellular coupling mechanism was not sensitive to pertussis
      toxin nor to the cAMP dependent protein kinase blocker (Rp)-cAMPS.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7620886
TI  - The spatiotemporal organization of auditory, visual, and auditory-visual evoked
      potentials in rat cortex.
AB  - Four placements of an 8 x 8 channel microelectrode array were used to map
      auditory, visual, and combined auditory-visual evoked potentials (AEP, VEP, AVEP)
      from a total of 256 electrode sites over a 7 x 7 mm2 area including most of
      somatosensory, auditory, and visual cortex in the right hemisphere of the rat.
      The unimodal AEP and VEP consisted of an archetypal response sequence
      representing a systematic spatial and temporal activation of primary and
      secondary sensory cortex. Spatiotemporal analysis of these waveforms indicated
      that they could be decomposed into a small number of spatial and temporal
      components; components that are related to patterns of specific and non-specific
      thalamocortical projections connecting the auditory and visual nuclei of the
      thalamus with primary and secondary auditory and visual cortex. These data
      suggest that the AEP and VEP complex are the cortical reflection of asynchronous
      activation of parallel thalamocortical projection systems. The areal distribution
      of the AEP and VEP also overlapped, primarily in secondary auditory and visual
      cortex, indicating that these regions contain populations of cells responding to
      either modality. Polymodal auditory-visual stimulation resulted in unique
      activation of two isolated populations of neurons positioned in secondary
      auditory and secondary visual cortex which were revealed by difference waveforms,
      computed by subtracting the sum of the AEP and VEP from the AVEP complex.
      Retrograde labeling of the polymodal zones indicated that they receive parallel
      thalamocortical projections primarily from non-specific auditory and visual
      thalamic nuclei including the medial and dorsal divisions of the medial
      geniculate nucleus (MGm and MGd), the suprageniculate nucleus (SGN), and the
      lateral posterior nucleus (LP). The polymodal zone in visual cortex also receives
      specific projections from the dorsal division of the lateral geniculate nucleus
      (LGd). These data conform to a general model of thalamocortical organization in
      which specific thalamic nuclei with a high degree of modality specificity make
      restricted projections to primary sensory cortex and parts of secondary sensory
      cortex, and association thalamic nuclei with a high degree of sensory convergence
      make more divergent cortical projections. Primary and secondary sensory cortex,
      as well as distinct zones of polysensory cortex appear to be activated in tandem
      via parallel thalamocortical projections. Thus, the cerebral cortex must have
      simultaneous access to both unimodal and polymodal sensory information.

PMID- 7620888
TI  - HIV-1 coat protein gp120-induced increases in levels of intrasynaptosomal
      calcium.
AB  - The effects of human immunodeficiency virus type-1 (HIV-1) coat protein gp120 on
      levels of intrasynaptosomal calcium ([Ca2+]i) were determined in rat cortical
      synaptosomes. gp120 at concentrations of > or = 400 pM, significantly (P < 0.05)
      increased levels of [Ca2+]i. Treatment with 20 mM KCl, reduced the concentrations
      of gp120 necessary to produce significant (P < 0.001) increases in [Ca2+]i. gp120
      evoked increases in [Ca2+]i were prevented either by treatment with dantrolene or
      by removal of extracellular calcium with BAPTA. The peak levels of gp120-induced
      increases in [Ca2+]i were not affected by calcium channel blockers lanthanum and
      nicardipine, by glutamate receptor antagonists MK-801 and NBQX, or by removal of
      endogenous glutamate with glutamate dehydrogenase. gp120-induced [Ca2+]i
      increases in presynaptic terminals may play a role in HIV-mediated effects in the
      central nervous system.

PMID- 7620889
TI  - Modulation of corticotropin-releasing hormone stimulated cyclic adenosine
      monophosphate production by brain cells.
AB  - Corticotropin-releasing hormone (CRH) is believed to have a role as an important
      brain neuroregulator acting through specific receptors coupled to adenylate
      cyclase in addition to its major role in regulating pituitary adrenocorticotropin
      synthesis and secretion. To study the potential modulatory effects of various
      regulators and the central effects of CRH, we studied the effects of phorbol
      ester myristate acetate (PMA), arginine vasopressin (AVP), corticosterone,
      dexamethasone, and progesterone on CRH stimulation of cyclic adenosine
      monophosphate (cAMP) production in extrahypothalamic forebrain cell cultures
      derived from day 17 gestation fetal rats. These cultures contain CRH receptors
      with similar characteristics as those in anterior pituitary and brain. CRH (10(
      9) - 10(-7) M) stimulated cAMP in a dose-dependent fashion and maximal
      stimulation was clearly seen at 10(-7) M CRH. Incubation of the cells with PMA
      (10(-7) M), a protein kinase C (PKC) agonist, had no effect on basal cAMP, but
      potentiated CRH-stimulated cAMP. AVP (10(-8), 10(-7) M) had no effect on basal
      nor CRH-stimulated cAMP accumulation. Corticosterone (10(-7), 10(-6) M) or
      dexamethasone (10(-9) - 10(-7) M) pre-incubation for 18 h did not diminish basal
      cAMP levels nor inhibit CRH-induced stimulation of cAMP. However, corticosterone
      inhibited CRH-induced cAMP production in anterior pituitary cells. Neither did
      exposure to progesterone (2 x 10(-8) M) modulate basal cAMP, CRH-induced cAMP
      production nor the potentiation of CRH stimulation by PMA. The data demonstrate
      that CRH receptors in dissociated fetal extrahypothalamic forebrain cell cultures
      are coupled to an adenylyl cyclase/cAMP second messenger system similarly as
      shown in studies with anterior pituitary membranes.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7620892
TI  - Parametric analysis of the effects of cocaine and cocaine pretreatment on
      dopamine release in the nucleus accumbens measured by fast cyclic voltammetry.
AB  - Fast cyclic voltammetry was used to measure dopamine (DA) release in the nucleus
      accumbens of anaesthetized rats, in response to electrical sine-wave stimulation
      of the ventral tegmental area. Voltammetric signals followed increases in either
      frequency (50-100 Hz), intensity (50-100 microA) or duration (0.5-5.0 s) of the
      stimulus. Cocaine administration (10 mg/kg) preferentially increased DA release
      by weak electrical stimuli. Cocaine pretreatment (3 x 10 mg/kg, two weeks
      earlier) preferentially increased DA release by stronger stimuli, and the effects
      of acute cocaine were potentiated in these animals. The effects of increasing
      stimulus duration conformed to first order kinetics. Cocaine pretreatment
      selectively increased the kinetic parameter representing maximal release, while
      acute cocaine administration preferentially decreased the parameter representing
      the stimulus duration eliciting half maximal release. The lack of statistical
      interaction between these two effects suggests that sensitization of the response
      to acute cocaine by cocaine pretreatment may simply reflect an increase in the
      size of the releasable pool of DA.

PMID- 7620891
TI  - Mixture suppression without inhibition for binary mixtures from whole cell patch
      clamp studies of in situ olfactory receptor neurons of the spiny lobster.
AB  - Whole cell patch clamping was used to investigate mechanisms of mixture
      suppression for in situ olfactory receptor neurons (ORNs) of the spiny lobster
      Panulirus argus. We used a set of single compounds and binary mixtures that have
      been used in previous biochemical studies of receptor-odorant binding,
      electrophysiological studies of spiking output from ORNs, and behavioral studies.
      These odorants were adenosine 5'-monophosphate (AMP), betaine (Bet), L-cysteine
      (Cys), L-glutamate (Glu), taurine (Tau), ammonium chloride, D,L-succinate, binary
      mixtures of these compounds, as well as a 33-component artificial oyster mixture
      (AOM). For the 40 ORNs studied, these stimuli more frequently elicited inward
      than outward currents. AMP, Glu, Tau and Bet evoked the largest and most numerous
      inward currents; Cys most commonly evoked outward currents. Na+ was an important
      charge-carrying ion for the Glu-evoked response in one ORN and the Bet-evoked
      response in another ORN. Mixture suppression, defined conservatively in this
      study as cases where the response to a binary mixture was less than the response
      to the more excitatory component of that mixture, was observed in 6 ORNs. In all
      6 cases, neither component of the mixture evoked an outward conductance (i.e.
      neither was inhibitory). Five of these cases of mixture suppression involved a
      mixture containing two excitatory compounds (i.e. producing inward conductances):
      four ORNs were excited by both Glu and AMP, and one ORN was excited by both Tau
      and Glu. One case of mixture suppression occurred for a compound (Tau) tha did
      not produce a current when presented alone but which when added to Bet suppressed
      the inward current generated by Bet. Mechanisms for these suppressions are
      discussed, including inhibition of receptor binding by the components of a binary
      mixture and effects on second messengers or ion channels.

PMID- 7620890
TI  - Preservation of autoregulatory cerebral vasodilator responses to hypotension
      after inhibition of nitric oxide synthesis.
AB  - Effects of inhibition of nitric oxide (NO) synthesis on the cerebrovascular
      autoregulatory vasodilator response to hypotension were studied in conscious
      rats. Cerebral blood flow (CBF) was determined with [14C]iodoantipyrine in a
      saline-treated control group and in three groups following inhibition of NO
      synthase activity by twice daily intraperitoneal injections of 50 mg/kg of NG
      nitro-L-arginine methyl ester (L-NAME) for four days. In the saline-control group
      (n = 8) and in the L-NAME-treated Group (a) (n = 8) CBF was determined while
      systemic mean arterial blood pressure (MABP) remained at its resting level (means
      +/- S.D., 128 +/- 6 and 151 +/- 11 mmHg, respectively). In the other groups CBF
      was determined after MABP was reduced by blood withdrawal to 118 +/- 9 and 88 +/-
      8 mmHg in Groups (b) (n = 8) and (c) (n = 8), respectively. Despite the elevated
      MABP, global CBF was significantly lower in L-NAME-treated Group (a) than in the
      saline-controls (P < 0.005), indicating cerebral vasoconstriction resulting from
      inhibition of NO synthesis. Global CBF was not significantly reduced further in
      the two groups with hypotension. Local CBF in the hypotensive rats showed no
      significant reductions below values in L-NAME-treated control rats (Group (a)) in
      31 of 32 brain structures; the only exception was in the auditory cortex of the
      severely hypotensive rats (Group (c)). The autoregulatory mechanism for cerebral
      vasodilatation to compensate for reduced arterial blood pressure is maintained
      following inhibition of NO synthesis.

PMID- 7620893
TI  - Progesterone, but not estrogen, modulates the cAMP system mediated ir-beta
      endorphin secretion and POMC mRNA expression from rat hypothalamic cells in
      culture.
AB  - It is now evident that hypothalamic beta-endorphin (beta EP) modulates
      reproductive physiology at the central level by inhibiting the function of
      neurons producing gonadotropin-releasing hormone (GnRH). Increasing evidence
      suggests that gonadal steroids, which play an important role in the long-loop
      negative feedback on the hypothalamus-pituitary-gonadal axis, may exert its
      indirect inhibitory action through modulating the production and release of
      hypothalamic beta EP. However, it remains unclear whether progesterone or
      estrogen alone or their combination is important to exert this effect. Employing
      long-term monolayer neonatal hypothalamic cell cultures, we reported here that
      whereas progesterone significantly enhanced forskolin-, N6,2'-O
      dibutyryladenosine-3'5'-cyclic monophosphate [(Bu)2cAMP]-, 3-isobutyl-1
      methylxanthine (IBMX)- or cholera toxin-stimulated immunoreactive (ir)-beta EP
      release from cultures treated daily for 4 consecutive days, the steroid alone
      produced little effect. This potentiation of progesterone was time-related and
      dose-dependent with an EC50 value of the steroid being approximately 25 nM; at
      this concentration the steroid increased ir-beta EP secretion about 1.6 times (P
      < 0.05) that induced by 5 microM forskolin alone. Similar effects were also
      observed for POMC mRNA levels in cultures subjected to 6 h of the above treatment
      regime. This potentiating effect appears specific as it can be mimicked by
      progestin, a progesterone receptor agonist and blocked by the progesterone
      receptor antagonist RU38486, but not RU28318, a mineralocorticoid receptor
      antagonist. Furthermore, beta-estradiol alone failed to exert a significant
      effect on basal, forskolin-induced or on forskolin and progesterone co-stimulated
      beta EP release or POMC mRNA levels in hypothalamic cell cultures.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7620894
TI  - Effect of food deprivation on glutathione and amino acid levels in brain and
      liver of young and aged rats.
AB  - The effect of short-term food deprivation on glutathione (GSH) and amino acid
      levels in brain regions of young and aged rats was compared with changes observed
      in liver. Animals aged 3 months and 24 months were deprived of food for 48 h. GSH
      and amino acid levels from cerebral cortex, cerebellum, pons medulla, and liver
      were assayed and compared with levels in animals of the same age fed normal
      diets. In liver in both young and old rats, GSH levels fell 30%, from 13 mumol/g
      tissue to 8.7 mumol/g tissue. Significant changes were observed in other amino
      acids, including an increase of 30-50% in methionine, glycine, and glutamine, and
      a decrease of 30-50% in alanine in liver of both young and aged rats, and a 4
      fold increase in taurine in young. In brain, little change was observed upon food
      deprivation. No decrease was observed in GSH, and only small changes were
      observed in other amino acids. In the aged animal aspartate, glutamate, and
      alanine levels were slightly lower; tyrosine in cerebellum was reduced by 30%,
      and both glycine and tyrosine in the pons medulla were reduced by 20-30%. In the
      brain areas examined, levels of GSH ranged from 1-2 mumol/g in young and 0.8-1.4
      mumol/g in old; with levels in pons medulla being lower than those in cerebral
      cortex. In brain, in contrast to liver, levels were scarcely affected by short
      term food deprivation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7620895
TI  - Inhibitors of lipid peroxidation protect cultured neurons against cyanide-induced
      injury.
AB  - We tested the 21-aminosteroid U-74500A and the 2-methylaminochroman U-83836E, two
      potent inhibitors of lipid peroxidation, for their protective efficacy against
      cyanide- or Fe2+/Fe(3+)-induced damage of cultured neurons from chick embryo
      telencephalon. U-74500A (0.1-10 microM) as well as U-83836E (0.01-10 microM)
      reduced cyanide-induced neurotoxicity, indicating that lipid peroxidation plays
      an important role in the genesis of cyanide-induced neuronal injury. Both U
      74500A and U-83836E, but not the NMDA antagonist dizocilpine (1 microM, prevented
      Fe2+/Fe(3+)-induced neuronal degeneration.

PMID- 7620896
TI  - Early cytoskeletal changes as shown by Alz-50 are not accompanied by decreased
      neuronal activity.
AB  - The nucleus tuberalis lateralis (NTL) is located in the basolateral part of the
      hypothalamus and is only present as a well-delineated nucleus in human and higher
      primates. In Alzheimer's disease (AD), NTL neurons show strong early cytoskeletal
      alterations, as revealed by the antibody Alz-50, but practically no senile
      plaques or neurofibrillary tangles. To study whether the activity of NTL neurons
      decreases when cytoskeletal changes appear, i.e., during aging and in AD, we
      applied a polyclonal antibody raised against the medial cisternae of the Golgi
      apparatus (GA). The size of the GA and the cell profile of NTL neurons, two
      established parameters for neuronal activity, were measured by an image analysis
      system. No significant change in the size of the profiles of the GA or of the
      neurons was observed in this nucleus during aging or AD. Earlier studies have
      shown that there is no decrease in cell number in the NTL in AD. We conclude that
      in the NTL an early hallmark of AD, i.e., cytoskeletal changes as stained by Alz
      50, does not correlate with decreased neuronal activity, as reflected by the size
      of the GA, nor with a decrease in cell number. In addition, we found that the
      very early occurring and abundant presence of lipofuscin in NTL neurons does not
      go together with decreased neuronal activity.

PMID- 7620897
TI  - Effect of capsaicin on micturition and associated reflexes in chronic spinal
      rats.
AB  - The role of capsaicin-sensitive bladder afferents in micturition was studied in
      unanesthetized chronic spinal rats. Reflex voiding in response to tactile
      stimulation of the perigenital region appeared 5-9 days after spinal cord injury
      (SCI) whereas voiding induced by bladder distension occurred 2-3 weeks after SCI.
      The frequency and amplitude of reflex bladder contractions recorded under
      isovolumetric conditions were similar in chronic spinal and urethane-anesthetized
      CNS-intact rats. However, cystometrograms (CMGs) performed 6-8 weeks after SCI
      revealed that the chronic spinal rats had larger bladder capacities (1.86 ml)
      than CNS-intact rats (0.48 ml) and also exhibited multiple, small-amplitude,
      nonvoiding bladder contractions that were not detected in CNS-intact rats.
      Administration of capsaicin (50 mg/kg s.c.) acutely (onset 14-40 min) suppressed
      reflex bladder activity induced by bladder distension or by perigenital
      stimulation in chronic spinal animals. However, pretreatment of chronic spinal
      rats with capsaicin (125 mg/kg s.c.) 4 days before the experiment did not depress
      voiding reflexes or change bladder capacity but did eliminate the nonvoiding
      contractions. Inhibition of reflex bladder contractions by mechanical stimulation
      of rectoanal canal or the uterine cervix-vagina was not altered by pretreatment
      with capsaicin. These data indicate that capsaicin-sensitive bladder afferents
      are not essential for the initiation of reflex micturition in chronic spinal
      rats. However, these afferents do contribute to hyperactivity of the bladder
      during the filling phase of the CMG. Thus, capsaicin-sensitive bladder afferents
      should be evaluated as possible targets for the pharmacological treatment of
      bladder hyperreflexia in patients with SCI.

PMID- 7620899
TI  - Muller cell survival and proliferation in response to medium conditioned by the
      retinal pigment epithelium.
AB  - Muller cells have been implicated in the pathogenesis of proliferative
      vitreoretinopathy and subretinal scar formation; however, the source(s) and
      signal(s) responsible for their activation are unknown. This study was undertaken
      to determine if the retinal pigment epithelium (RPE) could be involved in this
      signaling process by studying its effects on Muller cell survival and division in
      vitro. A pure population of Muller cells isolated from 1-2 day Long-Evans rats
      was seeded at low density and treated with medium conditioned by neonatal rat RPE
      (RPE-CM) or a nonconditioned, defined medium. By day 3, Muller cells cultured in
      RPE-CM increased in number 2-fold. These cells survived up to 21 days, which was
      the longest time tested. In contrast, cell number decreased in control wells 75%
      by day 3, and 100% by day 4. The RPE-mediated survival and proliferation of the
      Muller cells occurred in a dose-dependent manner. The mitogenic response was
      specific for the RPE when compared with fibroblasts and non-retinal epithelial
      cells. Heat and trypsin treatment of the RPE-CM completely abolished its survival
      and mitogenic activity. These findings demonstrate the establishment of an in
      vitro model which can be used to investigate RPE-Muller cell interactions. This
      study also provides evidence for RPE involvement in Muller cell interactions.
      This study also provides evidence for RPE involvement in Muller cell survival and
      proliferation.

PMID- 7620898
TI  - Developmental switch in the hippocampal serotonin receptor linked to
      phosphoinositide hydrolysis.
AB  - 5-HT2A and 5-HT2C receptors couple to the phosphoinositide hydrolysis signal
      transduction pathway. The present pharmacological analyses provide evidence for a
      switch in the functional 5-HT receptor in rat hippocampus (from 5-HT2A to 5-HT2C)
      between the first and third weeks of life. Spiperone and MDL 100,507, antagonists
      that bind with 300- to 1000-fold higher affinity to 5-HT2A receptors, blocked 5
      HT-induced phosphoinositide hydrolysis in hippocampi of 7-day-old, but not 21-day
      old, rats. In contrast, the non-selective 5-HT2A/2C receptor antagonists,
      mesulergine and mianserin, blocked 5-HT-mediated phosphoinositide hydrolysis in
      both 7- and 21-day-old rats. These results suggest that the 5-HT-induced
      phosphoinositide hydrolysis signal in hippocampus of 7-day-old rats is mediated
      predominantly by 5-HT2A receptors, while in 21-day-old rats the phosphoinositide
      hydrolysis signal is mediated in large part by 5-HT2C receptors. Neither 5-HT2A
      or 5-HT2C receptor mRNA nor the binding site densities of the two receptors were
      altered between the two ages, ruling out developmental changes in receptor
      density as an explanation for the observed differences. We conclude therefore
      that the hippocampal 5-HT receptor that links to phosphoinositide hydrolysis
      switches during postnatal development of rats, perhaps reflecting differences in
      the coupling of 5-HT2A and 5-HT2C receptors to intracellular effector molecules.

PMID- 7620900
TI  - Longitudinal variation in cell density and mossy fiber reorganization in the
      dentate gyrus from temporal lobe epileptic patients.
AB  - Variation in cell loss and mossy fiber reorganization was examined along the
      longitudinal axis of the dentate gyrus from temporal lobe epileptic (TLE)
      patients. Previous evidence has indicated that the anterior hippocampus is prone
      to seizure activity. We compared granule and hilar cell number in addition to
      Timm stain density of the molecular layer and hilus in more anterior and more
      posterior specimens of hippocampus obtained from patients surgically treated for
      intractable epilepsy by the removal of the anterior half of the hippocampus.
      Granule cells/mm in the more anterior specimen were less than or equal to those
      in the more posterior specimen locations in 77% of the patients, while there was
      no significant difference in hilar neuron density between the two blocks. These
      results demonstrate a significantly greater pathology in the granule cell layer
      in more anterior specimens and no difference in pathology for hilar neurons.
      Molecular layer Timm stain density was significantly greater in the more anterior
      specimen of 71% of the patients. The molecular layer Timm stain density ratio was
      inversely related to hilar cell density in more anterior specimens, whereas in
      more posterior specimens there was no significant relationship with hilar cell
      density. Our observations show that although differences exist among TLE patients
      for these neuroanatomic measures, pathology was greater in more anterior
      specimens. The latter result is consistent with the conclusion that seizure
      activity may originate in the anterior region of the hippocampus in a majority of
      patients.

PMID- 7620901
TI  - Expression of the conditioned NK cell activity is beta-endorphin dependent.
AB  - We are interested in identifying the pathways which are responsible for
      triggering the conditioned enhancement of natural killer (NK) cell activity.
      Earlier studies have suggested that central opioid(s) are involved in eliciting
      the expression of the conditioned NK cell activity. The purpose of this study was
      to identify the central opioid peptides that allow the central nervous system
      (CNS) to communicate with the immune system. Mediators that activate the efferent
      pathway of communication between the CNS and immune system was examined by
      injection of the mediator via the cisterna magna (CM). Conditioning was used as a
      tool to show that the bi-directional communication between the CNS and the immune
      system does take place. We found that beta-endorphin but not dynorphin could
      stimulate NK cell activity, when beta-endorphin or dynorphin was injected into
      the CM. In addition, when anti-beta-endorphin or anti-dynorphin antibody was
      injected into the conditioned animals via CM the conditioned response was blocked
      by anti-beta-endorphin but not by anti-dynorphin antibody. These observations
      suggest that beta-endorphin appears to be one of the signals that is induced in
      the brain at the CS recall step of the conditioned response to trigger the
      elevation of NK cell activity.

PMID- 7620902
TI  - Age-related alterations in energy metabolism contribute to the increased
      vulnerability of the aging brain to anoxic damage.
AB  - Aging increases the vulnerability of brain tissue to anoxia and ischemia. We
      investigated whether age-related alterations in energy metabolism underlie this
      increased vulnerability. Energy metabolism was manipulated in hippocampal slices
      from Fischer 344 rats of ages 6-9 (young adult), 16-19 (middle-aged adult), and
      26-29 (aged adult) months by altering glucose concentrations or by using lactate
      instead of glucose as the metabolic substrate. Extracellular K+ activity (K+o)
      and synaptic excitability were monitored in stratum pyramidale of hippocampal
      subfield CA1. Aging diminished how well increasing concentrations of glucose
      delayed onset of anoxic depolarization and improved postanoxic recovery of K+o
      homeostasis and synaptic transmission. Hippocampal slices from all age groups
      responded to anoxia similarly when lactate was present instead of glucose. Also,
      no age-related differences were seen in normoxic ATP and phosphocreatine levels.
      These results suggest that an age-related decline in the glycolytic capacity of
      brain cells contributes to earlier onset of anoxic depolarization and poorer
      recovery of ion homeostasis and synaptic transmission in aging brain tissue.

PMID- 7620903
TI  - Cadmium chloride (CdCl2)-induced metallothionein (MT) expression in neonatal rat
      primary astrocyte cultures.
AB  - Metallothionein (MT) protein and mRNA levels were studied following exposure of
      rat neonatal primary astrocyte cultures to cadmium chloride (CdCl2). MT mRNA was
      probed on Northern blots with a 32P labeled synthetic cDNA probe specific for rat
      MT mRNA. The probe hybridizes to a single mRNA with a size appropriate for MT,
      approximately 550 bases. Expression of MT-I mRNA in astrocyte monolayers exposed
      to 2 x 10(-6) M CdCl2 for 6 h was increased approximately 5-fold (9.7
      fg/micrograms total RNA) over MT-I mRNA levels in controls (2 fg/micrograms total
      RNA). MT-I mRNA could also be detected in untreated cells, suggesting
      constitutive MT expression in these cells. Western-blot analysis revealed a
      marked increase in MT protein levels upon exposure to CdCl2 (1 x 10(-6) M; 96 h).
      Consistent with the constitutive expression of MTs both at the mRNA level and
      protein level, we have also demonstrated a time-dependent increase in MT
      immunoreactivity in astrocytes exposed to CdCl2. The present study suggests that
      astrocytes constitutively express MTs, and that MT-induction by CdCl2 may be an
      example of a generalized increase in MTs in response to heavy metal exposure,
      thus protecting astrocytes, and perhaps also indirectly, juxtaposed neurons from
      the neurotoxic effects of heavy metals.

PMID- 7620904
TI  - Developmentally-regulated lectin binding in the embryonic mouse telencephalon.
AB  - Cell-surface carbohydrate epitopes are important determinants in cell-cell and
      cell-matrix interactions, and oligosaccharide groups are structural components of
      many growth factor receptors and cell adhesion molecules. These epitopes may
      participate in the regulation of stem cell proliferation and differentiation
      during central nervous system development. To further understand these cellular
      phenomena, it is important to define the changes in neuroepithelial cell-surface
      carbohydrate expression during development. We used a panel of fluorescein
      conjugated lectins to label live, freshly dissociated cells from the embryonic
      day 11 to 18 (E11 to E18) mouse telencephalon. The intensity and heterogeneity of
      lectin labeling was assessed by flow cytometry. The lectins that we examined
      exhibited widely varying levels of labeling intensity. Lectins with the highest
      degree of binding included cholera toxin B subunit (CTB), which binds primarily
      to the gangliosides GM1 and GD1b, phaseolus vulgaris erythroagglutinating lectin
      (PHA-E), which binds to a variety of cell adhesion molecules, and wheat germ
      agglutinin (WGA). Many lectins showed increasing labeling intensity and cellular
      heterogeneity as development progressed. To determine if the observed cellular
      heterogeneity in lectin binding reflected biological differences in
      neuroepithelial cell subpopulations, cells from the E14 telencephalon were
      separated into two populations based on their intensity of CTB labeling using a
      fluorescence activated cell sorter. The population of weakly CTB labeled cells
      contained more than four times as many cells in S-phase of the cell cycle than
      the population of intensely CTB labeled cells. These observations suggest that
      lectin cytochemistry and flow cytometry can be useful in identifying specific
      cell subpopulations of neuroepithelial precursor cells during development,
      allowing their isolation and characterization in vitro.

PMID- 7620905
TI  - Ventrostriopallidal functional interconnections with cortical and quasi-cortical
      regions.
AB  - A total of 287 neurons were antidromically driven in quasi-cortical regions,
      i.e., anterior olfactory nucleus (24%), basolateral amygdala (13%), main
      olfactory bulb (4%), prefrontal cortex (37%), and in the hippocampal formation
      (22%) following macro- and microstimulation of the rat's ventrostriopallidal
      region (VSPR). In addition, a substantial number of units (n = 175) were also
      transynaptically affected in all these structures by shocks delivered to the
      VSPR. Excitatory effects were detected in 50 neurons (56.1% of responsive cells),
      36 cells (40.4%) responding with inhibition of spontaneous discharges.
      Conversely, stimulation of cortical and quasi-cortical regions antidromically
      discharged (n = 37) or transynaptically affected (n = 151) units in the VSPR; 168
      neurons were not responsive to VSPR stimulation. Axon collateralization
      (branching) of 14 neurons in anterior olfactory nucleus, basolateral amygdala,
      and hippocampal formation was revealed with the use of the reciprocal collision
      test. Conduction properties of 35 neurons, evaluated by paired-pulse stimulation,
      indicated that only 26% showed a significant increase in conduction velocity and
      a decrease in threshold during the supernormal phase. The present findings
      confirm and extend previous neuroanatomical studies that have, first, described
      strong interconnections between the neocortex and striatal structures, and
      second, that the VSPR as suggested by previous structural, hodological, and
      histochemical studies, seems to maintain a more close relationship with olfactory
      related structures than hitherto suspected.

PMID- 7620906
TI  - Habituation of the galvanic skin response to tone as a function of age.
AB  - Habituation of the galvanic skin response (GSR) to tone in male college students
      varying in age from 18-39 years old was examined. Older subjects habituated more
      slowly to tone than did younger ones. This confirmed our past work on habituation
      of the GSR to electric shock. The GSR is shown to be a sensitive and reliable
      measure of small differences in age as it affects learning. The clinical
      usefulness of this quantitative and sensitive measure in detecting small and
      early changes in learning and memory deficits associated with age and dementia is
      discussed.

PMID- 7620907
TI  - Catecholaminergic region A15 in the bovine and porcine hypothalamus.
AB  - Magnocellular perikarya within the retrochiasmatic division of the supraoptic
      nucleus of bovine and porcine hypothalami were immunoreactive (ir) with antiserum
      against tyrosine hydroxylase (TH), but not dopamine-beta-hydroxylase (DBH). Few
      cells in this region were also immunoreactive for vasopressin (VP) or oxytocin
      (OT). In contrast, the main division of the supraoptic nucleus contained numerous
      perikarya immunoreactive for VP and OT, but not TH nor DBH. Both the
      retrochiasmatic and principal divisions of the supraoptic nuclei contained TH-
      and DBH-ir fibers and varicosities. This region in bovine and porcine hypothalami
      corresponds to the ventral A15 catecholaminergic (dopamine-producing) cell group.

PMID- 7620908
TI  - Nicotine-induced acute tolerance: studies involving schedule-controlled behavior.
AB  - The major goal of the present study was to examine acute tolerance to nicotine
      induced disruption of operant behavior following a single, noncontingent
      injection. Rats were trained to lever press for food reinforcement under a fixed
      ratio-30 schedule. Once trained, rats were injected with either saline or
      nicotine (0.8 mg/kg) in their home cages. After either a 90- or 180-min delay,
      each rat was injected with nicotine (0.4 mg/kg) and placed in the operant chamber
      for a 30-min behavioral evaluation session. This experiment was replicated with
      slight modifications 1 week later. The results of the present study suggest that
      0.8 mg/kg of nicotine produces acute tolerance to the response rate decreasing
      effects of 0.4 mg/kg of nicotine. Because the tolerance-producing dose of
      nicotine was injected while rats were not in the test environment, they did not
      have an opportunity to practice the target behavior while under the influence of
      the drug. Hence, the acute tolerance observed in this study appears to be, at
      least partly, pharmacological (vs. behavioral) in nature, and may be related to a
      desensitization of central nicotinic acetylcholinergic receptors (nAChRs).

PMID- 7620909
TI  - Paucity of c-fos expression in the medial preoptic area of prenatally stressed
      male rats following exposure to sexually receptive females.
AB  - Normal male rats display high levels of sexual activity when paired with sexually
      receptive females, a behavior regulated, in large part, by the medial preoptic
      area (MPOA). It has been documented that onset of c-fos proteins in the MPOA
      accompanies sexual behavior. Because prenatal stress (PS) demasculinizes sexual
      behavior in male rats, the present study examined whether such effects might be
      accompanied by a decrease in the neuronal activation in MPOA associated with
      sexual behavior. Adult prenatally stressed (P-S) and unstressed control males
      were paired with sexually receptive females, and sexual behavior allowed to
      commence. After a single mount, the pair was separated by a partition for the
      remainder of an hour, at the end of which the male was killed and the brain
      processed for c-fos immunocytochemistry; quantification was performed by means of
      computerized image analysis. P-S males expressed significantly less c-fos
      activity in the region of the MPOA, compared to nonstressed control males. Thus,
      the sexual deficits associated with P-S males may be due to a relative dearth of
      activity in the MPOA at the neuronal level. Coupled to earlier work showing
      decreased luteinizing hormone secretion in P-S males under similar conditions,
      the present data suggest a constellation of factors that contribute to PS-induced
      deficits in sexual behavior.

PMID- 7620910
TI  - The effect of environmental odors emanating from commercial swine operations on
      the mood of nearby residents.
AB  - The effect of environmental odors emanating from large-scale hog operations on
      the mood of nearby residents was determined using the POMS (Profile of Mood
      States). The scores for six POMS factors and the TMD (total mood disturbance
      score) for 44 experimental subjects were compared to those of 44 control subjects
      who were matched according to gender, race, age, and years of education. The
      results indicated a significant difference between control and experimental
      subjects for all six POMS factors and the TMD. Persons living near the intensive
      swine operations who experienced the odors reported significantly more tension,
      more depression, more anger, less vigor, more fatigue, and more confusion than
      control subjects as measured by the POMS. Persons exposed to the odors also had
      more total mood disturbance than controls as determined by their ratings on the
      POMS. Both innate physiological responses and learned responses may play a role
      in the impairment of mood found here.

PMID- 7620911
TI  - Neuronal regeneration and estrous cycle restoration after locus coeruleus
      periventricular gray substance section.
AB  - The locus coeruleus (LC) was anatomically separated from the periventricular gray
      substance (PVG) by means of knife cuts in the adult female rat presenting regular
      estrous cycling. This resulted in a transient suppression of the estrous cycling
      that lasted 10-13 days after surgery. After this period, irregular or regular
      cycling activity was observed. The regular cycling was restored 30-45 days after
      the knife cuts. Golgi impregnation of some of the brains of these rats revealed
      regenerative elements in the knife-cut-insulted area. Thus, blood vessels,
      macrophagic-like elements, and glial-like elements were observed in close
      relation with the knife-cut pathway. Additionally, well-defined stained neurons
      typical of the LC and PVG were observed in close proximity to the knife-cut
      pathway. Dendritic and axon projections towards the insulted area were observed.
      Well defined axons were seen across the knife-cut pathway. These data support,
      first, that the LC-PVG communication is part of a circuitry for the modulation of
      gonadotropic activity, and second, that in the restoration of the estrous
      cyclicity after the knife cut, regenerative processes leading to a LC-PVG
      functional reconnection occurred after the knife cut.

PMID- 7620912
TI  - Temporal changes of c-fos expression in oxytocinergic magnocellular
      neuroendocrine cells of the rat hypothalamus with restraint stress.
AB  - The present experiments were undertaken to examine c-fos expression in
      magnocellular neuroendocrine cells (MNCs) of the rat hypothalamus with restraint
      stress using dual immunohistochemistry for c-fos and oxytocin. Restraint stress
      induced c-fos expression in oxytocinergic MNCs in the supraoptic nucleus (SON)
      and paraventricular nucleus (PVN). Quantitative immunohistochemical analysis
      revealed that percentages of c-fos-positive cells to oxytocin-immunoreactive MNCs
      in the SON and PVN maximally increased at 2 h after restraint stress had started,
      and began to decline in spite of the fact that the restraint of animals were
      continued. Similar results were obtained from time course of c-fos expression in
      parvocellular neurons of the PVN. When animals were released to move freely in
      their home cages following the 3-h restraint, the plasma levels of oxytocin
      declined to reach basal levels within 30 min and c-fos immunoreactivity in the
      hypothalamic MNCs and parvocellular neurons disappeared faster than those of the
      continually restrained. These results demonstrate that restraint stress induces c
      fos expression in oxytocinergic MNCs in the SON and PVN, and that time course of
      c-fos expression is transient even in the continuation of restraint stress.

PMID- 7620913
TI  - Convergence of afferents from the SLN and GPN in cat medullary swallowing
      neurons.
AB  - We demonstrated the convergence of information from the pharyngeal and laryngeal
      mucosa, transmitted by the glossopharyngeal nerve (GPN) and superior laryngeal
      nerve (SLN), in the nucleus of the tractus solitarius (NTS). First, the
      distribution of terminals of the GPN and SLN in the NTS was examined by an HPR
      tracing technique in cats, and the synapse formation of these neurons with NTS
      neurons was demonstrated by electron microscopy. The HRP-labeled SLN and GPN
      terminals were localized in a small area of the interstitial subnucleus of the
      NTS, slightly rostral to the obex, forming synapses with NTS neurons. Next, using
      extracellular recording in anesthetized cats, we determined whether or not
      swallowing-related neurons in the medulla oblongata receive peripheral inputs.
      Convergence of peripheral sensory inputs from the SLN and GPN was observed in
      more than 80% of the NTS cells. These results suggest that the NTS is not only a
      sensory-relay nucleus but also integrates information necessary for eliciting
      protective reflexes of the upper airway, such as swallowing.

PMID- 7620914
TI  - Maintenance of ultrastructural plasticity of the hypothalamic supraoptic nucleus
      in the ovariectomized rat.
AB  - In the present experiments, we examined the effect of ovariectomy on the
      increases in litter weight and structural plasticity of MNCs in the supraoptic
      nucleus (SON) during lactation. Female rats were ovariectomized 2 days after
      parturition, and the increases in litter weight were measured as the index of
      milk let-down from dams during lactation. The lactation period was elongated up
      to 6 weeks by providing new litter to obtain more apparent effects of the
      ovariectomy. There was no significant difference in the increases in litter
      weight between non-operated and ovariectomized females. After lactation for 6
      weeks, the ultrastructures such as juxtaposition (surface membrane apposition)
      and multiple synapses (terminals contacting with two or more postsynaptic
      elements) of MNCs in the SON in nonoperated and ovariectomized females were
      examined to compare with those of virgins. The percentage of juxtaposition and
      the number of multiple synapses significantly increased in nonoperated lactating
      females as compared with those of virgins. Ovariectomized rats showed similar
      structural changes to those of nonoperated females during lactation. Therefore,
      we conclude that ultrastructural plasticity of MNCs in the SON is maintained even
      in the absence of an ovary, and direct or indirect actions of suckling
      stimulation may be important in maintaining the plasticity during lactation.

PMID- 7620916
TI  - The S100 protein family: history, function, and expression.
AB  - The S100 family of calcium binding proteins contains approximately 16 members
      each of which exhibits a unique pattern of tissue/cell type specific expression.
      Although the distribution of these proteins is not restricted to the nervous
      system, the implication of several members of this family in nervous system
      development, function, and disease has sparked new interest in these proteins. We
      now know that the original two members of this family, S100A1 and S100B, can
      regulate a diverse group of cellular functions including cell-cell communication,
      cell growth, cell structure, energy metabolism, contraction and intracellular
      signal transduction. Although some members of the family may function
      extracellularly, most appear to function as intracellular calcium-modulated
      proteins and couple extracellular stimuli to cellular responses via interaction
      with other cellular proteins called target proteins. Interaction of these
      proteins with target proteins appear to involve cysteine residues (one in S100A1
      and two in S100B), as well as a stretch of 13 amino acids, in the middle of the
      molecule called the linker region, which connects the two EF-hand calcium binding
      domains. In addition to the amino acid sequence and secondary structures of these
      proteins, the structures of the genes encoding these proteins are highly
      conserved. Studies on the expression of these proteins have demonstrated that a
      complex mixture of transcriptional and postranscriptional mechanisms regulate
      S100 expression. Further analysis of the function and expression of these
      proteins in both nervous and nonnervous tissues will provide important
      information regarding the role of altered S100 expression in nervous system
      development, function and disease.

PMID- 7620915
TI  - Amphetamine enhances memory retention and facilitates norepinephrine release from
      the hippocampus in rats.
AB  - The present study investigated the effects of intrahippocampal amphetamine on
      memory retention and the role of hippocampal norepinephrine (NE) in memory
      consolidation in rats. One-way inhibitory avoidance learning paradigm was
      adopted. Animals were trained to avoid the foot shock. The latency to step into
      the shock compartment was recorded as the retention measure. The ceiling score
      (full retention) was 600 s. Results indicated that intra-hippocampal injections
      of amphetamine produced a dose-dependent enhancement of memory retention with
      doses at 0.6 micrograms and 1.6 micrograms reaching a significant effect. The
      beta-adrenergic blocker propranolol, at a dose which did not affect retention
      alone (80 ng), antagonized the memory-enhancing effect of amphetamine. Along with
      this memory-enhancing effect, amphetamine also elevated the level of NE release,
      and this effect was significant in animals not showing a full retention score
      (nonresponders) than in animals showing a full retention score (responders), as
      assayed by in vivo microdialysis. Within the control group, the responders also
      had a higher level of NE than the nonresponders. All these results are probably
      due to the fact that responders have a higher level of NE release than
      nonresponders. The effect of amphetamine on NE release is, therefore, not as
      obvious in responders. These results together support our hypothesis that NE
      plays a facilitatory role in the memory process and amphetamine enhances
      retention performance, at least in part, through facilitation of hippocampal NE
      release.

PMID- 7620917
TI  - Quantitative autoradiographic localization of [3H]3-OH-PCP (1-(1(3
      hydroxyphenyl)cyclohexyl)piperidine) binding sites in rat brain.
AB  - Binding of a novel radioligand, [3H]3-OH-PCP (1(1(3-hydroxyphenyl)
      cyclohexyl)piperidine), to N-methyl-D-aspartate (NMDA) receptor-coupled and 
      uncoupled PCP sites was investigated in the rat brain. The highest densities of
      [3H]3-OH-PCP binding were observed in the hippocampal formation, notably in the
      stratum radiatum and oriens of CA1 region, and dentate gyrus. There were
      relatively high levels of binding in the olfactory system, superficial layer of
      cortices, the amygdala and the thalamus. In contrast, lower levels of binding
      were found in the globus pallidus, cerebellum, and brain stem, except for the
      superior colliculus. These findings demonstrate that [3H]3-OH-PCP binds to
      discrete regions within the rat brain. Its distribution is consistent with
      autoradiographic localization of [3H]TCP and [3H]MK-801 binding sites in the rat
      brain, suggesting that [3H]3-OH-PCP binds to NMDA/PCP ion-channel complexes in
      preference to sigma sites.

PMID- 7620918
TI  - Treatment of patients with acute myelogenous leukemia: review of clinical trials
      of the past decade.
AB  - We discuss the history and progress of treatment for acute myelogenous leukemia
      (AML) in children as it has evolved over the past decade. We review the results
      of clinical trails for children with AML and examine the major strategies that
      have contributed to progresses in the treatment of this disease. Prior to the
      1970's, nearly every child with AML died. Modern intensive chemotherapy, bone
      marrow transplantation, and advanced supportive care of critically ill patients
      have improved the outlook for children with this fatal disease. CONCLUSION:
      Although it represents only 15-20% of all childhood acute leukemias, > 30% of
      deaths from leukemia are still a consequence of AML, and only 30-40% of children
      with newly diagnosed AML are expected to achieve a long-term remission. Greater
      advances in treatment are expected as headway is made in understanding the
      complex biology of this heterogeneous disease.

PMID- 7620919
TI  - Acute promyelocytic leukemia.
AB  - Significant advances have occurred in the diagnosis, treatment, and long-term
      outcome of patients with acute promyelocytic leukemia (APL). The purpose of this
      review is to describe the molecular genetics of this disease, the use of all
      trans retinoic acid (ATRA) in clinical trials of APL, and the clinical and basic
      research questions for future investigation. Findings of clinical studies in
      mainland China using ATRA as induction therapy for patients with APL concurrent
      with laboratory characterization of the molecular changes in APL have led to
      worldwide clinical trials of ATRA in the treatment of patients with APL. Major
      advances in understanding the molecular biology and genetics of APL have occurred
      over the past 5 years. These findings have been translated into novel treatment
      strategies using all-trans retinoic acid as a differentiation agent in the
      induction phase of therapy resulting in improved long-term outcome, reduced
      morbidity, and lower costs for patients with APL. Advanced molecular techniques
      are being employed for diagnosis and for monitoring of patient response to
      treatment.

PMID- 7620920
TI  - Bone marrow transplantation for children with acute myelogenous leukemia.
AB  - This article reviews bone marrow transplantation (BMT) in acute myelogenous
      leukemia (AML) of children from adoption of allogeneic BMT for children in first
      complete remission to the present where autologous BMT, marrow purging, and
      alternative donors are the major issues. Match related BMT in first remission
      achieved long-term disease free survival in well over half the young patients.
      However, as only 25-30% of patients have a matched sibling donor, other options
      for BMT has been explored, including autologous BMT and unrelated donor BMT.
      There are many issues that require further study regarding autologous transplant,
      including the efficacy and benefits of marrow purging. Unrelated donor
      transplants offer encouraging results in suitable patients, but bring with them
      the increased risk of complications. BMT is also successful in some children in
      second remission or who have refractory disease. A recent development in the
      transplant of children with AML is the use of nonradiation-containing
      conditioning regimens to avoid potential long-term sequelae of total body
      irradiation. Nonradiation regimens appear to be as efficacious as radiation
      containing regimens for these children. The superiority of BMT over chemotherapy
      has recently been challenged, as improved supportive care and extremely intensive
      therapy have resulted in approximately 75% of children achieving a remission and
      30-40% of patients surviving. Recent studies have focused upon answering the
      question regarding the role of BMT in children in first remission. Strategies to
      improve the outcome of BMT and comparison sequelae of BMT to those on high dose
      chemotherapy are issues that need to be addressed.

PMID- 7620921
TI  - New agents for treatment of children with acute myelogenous leukemia.
AB  - Over the past 15 years, daunorubicin, cytosine arabinoside and, to a lesser
      extent, 6-thioguanine and etoposide have become the standard agents used to treat
      patients with acute myelogenous leukemia (AML). These agents have been used in
      various combinations and schedules with only small improvements in overall
      outcome because few other agents with promise were available. This situation has
      changed over the past few years so that today there are a number of new agents
      that have the potential to supplement or replace the standard drugs. Idarubicin,
      mitoxantrone, amsacrine, homoharringtonine, 2-chlorodeoxyadenosine, fludarabine,
      carboplatin, retinoids, colony stimulating factors, and interleukin-2 are
      discussed.

PMID- 7620922
TI  - Infections in children with acute myelogenous leukemia. Concepts of management
      and prevention.
AB  - The child with acute myelogenous leukemia (AML) is at high risk for infection,
      especially during the induction phase of therapy. Appreciation of special risk
      factors and the changing spectrum of infecting pathogens is critical to
      development of the most appropriate initial evaluation and therapy for these
      children. Based on the available data in pediatrics, and extrapolation from
      studies in adult populations, we make recommendations for the initial empiric
      management of the febrile child with AML, the proper use of vancomycin, and
      management of special infectious complications related to central venous catheter
      use. Fungal infections are rapidly becoming the single most serious supportive
      care problem for children with AML. Optimal initial empiric therapy, treatment of
      proven systemic infections, and current status of attempts at prophylaxis are
      reviewed. Finally, the issue of colony stimulating factor use in AML is broached.
      Hopefully, studies underway will demonstrate the benefits and risks of these
      agents in AML. The time is long past due for large, well designed studies of
      supportive care in AML. Therapeutic trials addressing this very important aspect
      of the total care of the child with AML need to accompany the advancing new anti
      oncologic therapies of the disease.

PMID- 7620923
TI  - Case management. A means to improve quality and control the costs of cure in
      children with acute myelogenous leukemia.
AB  - Acute myelogenous leukemia (AML) is a costly disease to treat, as patients
      experience many hospital stays secondary to chemotherapy, the side effects of
      treatment, and bone marrow transplantation. The trend for some medical centers
      has been to reduce costs and increase quality through case management. The case
      manager uses critical pathways and one-on-one interaction to facilitate the
      patients' progress through the hospital system and to decrease delays and
      duplication. CONCLUSION: Case management and critical pathways could become an
      indispensable tool for the management of pediatric patients with cancer.

PMID- 7620924
TI  - Results of pediatric oncology group protocol 8104 for infants with stages D and
      DS neuroblastoma.
AB  - PURPOSE: We determined the complete response and survival rates for infants with
      disseminated (stage D) neuroblastoma that followed therapy identical to that for
      regional disease. In those infants whose disease excluded cortical bone
      metastases (stage DS), we determined complete response rates achieved either
      spontaneously or with stage D therapy. PATIENTS AND METHODS: Eighty-eight
      patients with metastatic disease received induction chemotherapy followed by a
      second operation, the results of which determined additional therapy. Twenty-five
      patients were observed after diagnosis, without chemotherapy, until a second
      operation. RESULTS: The complete response (CR) rates for patients with stage D
      disease after induction chemotherapy and postinduction surgery were 26% and 52%,
      respectively, and for immediately treated patients with stage DS disease 69% and
      77%, respectively. Fifty-four percent of initially observed patients with stage
      DS disease achieved CR after a second operation; 44% were never treated beyond
      these two operations. Five-year actuarial survival rates for patients with stage
      D and for all those with stage DS disease were 60% (SE = 6%) and 90% (SE = 5%),
      respectively. CONCLUSIONS: Improved survival rates for patients with stage D
      disease were achieved on this protocol but remained considerably lower than those
      for infants with less extensive disease. Rates of survival for patients with
      stage DS disease were achieved with therapy less aggressive than in published
      series.

PMID- 7620925
TI  - Age-related differences in a clot lysis assay after adding different plasminogen
      activators in a plasma milieu in vitro.
AB  - PURPOSE: The fibrinolytic system is involved in a wide variety of biological
      phenomena and differs physiologically in newborns compared to older children or
      adults. Because the newborn has hypoplasminogenemia and a possible existence of a
      dysfunctional plasminogen with normal adult levels of plasminogen activator
      inhibitor type 1 and alpha 2-antiplasmin and elevated levels of plasminogen
      activator inhibitor type 2, it could be expected that the response to standard
      concentrations and doses of plasminogen activators would be reduced. PATIENTS AND
      METHODS: We have studied the kinetics of in vitro fibrinolysis after adding
      different concentrations of streptokinase(SK), urokinase(UK), and recombinant
      tissue plasminogen activator(rt-PA) by use of a microtiter clot lysis assay.
      RESULTS: Geometrical dilution rows showed characteristic dose response curves.
      After clot formation a rapid lysis was seen with all plasminogen activators. The
      50% lysis time correlated to the plasminogen activator dose and showed no
      differences among normal adults, children aged 1-6 years, and children age 7-14
      years. Newborns demonstrated a significantly prolonged 50% lysis time with all
      urokinase concentrations. The 50% lysis time with recombinant tissue plasminogen
      activator and streptokinase was significantly prolonged only at high
      concentrations, whereas we could not see any differences at lower concentrations.
      CONCLUSION: The experience with thrombolytic agents in newborns is limited, and
      no controlled investigations have been reported. Our results of the fibrinolytic
      potential in a plasma milieu in vitro after adding different plasminogen
      activators can be helpful to establish dosage guidelines for thrombolytic therapy
      in newborns and older children.

PMID- 7620926
TI  - Ifosfamide/carboplatin/etoposide (ICE) for recurrent malignant solid tumors of
      childhood: a Pediatric Oncology Group Phase I/II study.
AB  - PURPOSE: The combination of ifosfamide (I) and etoposide (E) was useful in
      salvaging patients with recurrent/resistant malignant solid tumors of childhood.
      Carboplatin (C), active against a number of pediatric cancers, was added to I and
      E to form a three-drug combination called ICE to improve the response rate.
      PATIENTS AND METHODS: ICE, consisting of I 1.5 g/m2 plus E 100 mg/m2 i.v.q.d. x 3
      plus C i.v. on day 3 only, was given in 21-28-day intervals. C was started at 300
      mg/m2, and the dose was escalated in 25% increments, with three evaluable
      patients treated at each level. RESULTS: Ninety-two patients were enrolled in
      this phase I/II study between July 1990 and April 1993. A total of 331 courses of
      ICE was administered. Median courses of ICE received were three (range, 1-16).
      The maximum tolerated dose (MTD) for C when used in combination was found to be
      635 mg/m2. The response rate for ICE at the MTD for C was complete response (CR)
      26% and CR + partial response (PR) 53%. The response was even better in those who
      received C at the MTD: 32% achieving a CR and 63% a CR + PR. Pancytopenia was the
      dose-limiting toxicity. Thirteen episodes of bacterial infection were reported,
      none fatal. Only one patient developed a Fanconi-like syndrome. CONCLUSION: The
      MTD of C when used with I and E was found to be 635 mg/m2. The overall CR + PR
      rate for all patients treated at all C dose levels was 53%. Best responses were
      seen in non-Hodgkin's lymphoma, neuroblastoma, soft tissue sarcomas, and Wilms'
      tumor.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7620927
TI  - Detection of neoplastic clone in the hypoplastic and recovery phases preceding
      acute lymphoblastic leukemia by in vitro amplification of rearranged T-cell
      receptor delta chain gene.
AB  - This study assessed the clonality of hypoplastic and subsequent recovery phases
      before the development of overt leukemia by molecular genetic analysis. We
      describe a boy who had transient granulocytopenia and anemia before the
      development of acute lymphoblastic leukemia (ALL). Initially, his bone marrow was
      hypocellular with 23.6% of lymphoblastic cells, whereas subsequent marrow after
      the administration of granulocyte colony-stimulating factor (G-CSF) appeared
      almost normal without any lymphoblasts. At diagnosis, we found the rearrangement
      of T cell receptor (TCR) delta gene in the leukemic cell DNA by Southern blot
      hybridization. The junctional sequence of the V delta 2-D delta 3 recombination
      of leukemic cells obtained by polymerase chain reaction (PCR) was used for a
      clonospecific probe. Using the probe, the presence of leukemic clone in the
      materials before and after diagnosis was examined. We found that the
      clonospecific probe could detect one leukemic cell in 10,000 normal cells, and we
      demonstrated the presence of the leukemic clone at the initial hypoplastic and
      the subsequent recovery phase. The PCR method is very useful to confirm the
      presence of leukemic clone even in a retrospective analysis using low-quality
      materials and may be helpful to understand the pathogenesis of a smoldering
      preleukemic phase.

PMID- 7620928
TI  - Wilms tumor in a child with Down syndrome.

PMID- 7620929
TI  - Parents' views of a paediatric outpatient department.

PMID- 7620930
TI  - Intraosseous infusions in paediatric emergencies.

PMID- 7620931
TI  - Tuberculosis meningitis and cerebral tuberculoma.

PMID- 7620932
TI  - Nursing and stressful environments.

PMID- 7620933
TI  - Marshalling forces and winning the argument.

PMID- 7620934
TI  - Febrile convulsions.

PMID- 7620935
TI  - Mastering child health.

PMID- 7620936
TI  - Children's nurses in A&E.

PMID- 7620937
TI  - Elimination of environmental factors or elimination of individuals: biomarkers
      and prevention.

PMID- 7620938
TI  - Molecular approaches in toxicology: change in perspective.
AB  - Molecular approaches have attained a central position in modern experimental and
      human toxicology by providing the means to study basic underlying mechanisms.
      Molecular methods can be used to identify causal associations that would
      otherwise be obscure and to make better quantitative estimates of those
      associations at relevant levels of exposure. They may also make it possible to
      identify susceptible groups or individuals who are at risk of suffering the toxic
      effects of certain types of environmental and occupational agents. The use of
      transgenic animals in toxicology will improve our understanding of the role of
      toxic chemicals, such as carcinogens and mutagens, and their dosimetry and target
      organs. The use of molecular approaches in toxicology should thus result in
      better estimates of risks to human health.

PMID- 7620939
TI  - Individual expression of carcinogen-metabolizing enzymes: cytochrome P4502A.
AB  - Expression of enzymes metabolizing drugs, carcinogens, and other chemicals
      ("xenobiotics") is regulated by the interplay of genetic, host, and environmental
      factors, leading in human populations to a marked interindividual variability. On
      this basis it is speculated that individual differences in cancer susceptibility
      could be explained to a certain extent by interindividual differences in
      metabolic activation. CYP dependence of carcinogen activation is briefly
      reviewed; CYP2A6 as a more specific example and some consequences and corollaries
      are briefly discussed. At present, no consensus has been reached about the
      significance of interindividual differences (genetic or nongenetic) in carcinogen
      metabolism in cancer etiology. The likely reason is that chemically induced
      cancer is still a multifactorial, multistage disease involving numerous events
      before a clinically manifested disease develops. Molecular biological methods
      such as RFLP and PCR-based techniques as well as molecular dosimetry are making
      it possible to investigate the genetic background of individual subjects and
      environmental influences without biases caused by diseases, age, treatment, and
      other factors, which have plagued studies thus far.

PMID- 7620940
TI  - Genetic polymorphism of cytochromes P450 1A1, 2D6 and 2E1: regulation and
      toxicological significance.
AB  - Because of important roles of cytochromes P450 in the metabolic activation of
      many precarcinogens, extensive research in the past has focused on the
      relationship between the distribution of polymorphic variants of different
      isozymes of P450 and cancer susceptibility. In this respect three isozymes in
      particular have been studied, CYP1A1, CYP2D6, and CYP2E1. Both CYP1A1 and CYP2E1
      participate in the metabolism of many suspected as well as established
      carcinogens, whereas essentially only one carcinogenic substrate has been
      identified for CYP2D6. Polymorphic sites for the three CYP genes have been
      identified both in the open reading frame as well as in introns and the
      regulatory 5' region. In the present contribution we summarize the molecular
      epidemiological research relating CYP polymorphism to cancer susceptibility and
      in some cases to toxicity. An interesting polymorphism has been described on the
      phenotypic level for the inducibility of CYP1A1, a polymorphism that in some
      studies has been related to a mutation in the 3' flanking region of the CYP1A1
      gene. However, the genetic basis for this polymorphism might be inherited in the
      genes coding for proteins responsible for the induction of CYP1A1, ie, the Ah
      receptor or the ARNT protein. Data on lung cancer and CYP1A1 gene polymorphism
      indicate that carriers of genotypes associated with CYP1A1 inducibility are at
      higher risk for cancer, but that, at least for Caucasians, the recognized
      mutations probably identify only a fraction of the inducible individuals. The
      amount of DNA adducts correlates well in some studies to the individual activity
      registered for CYP1A1. CYP2D6 phenotype and genotype have mainly been related to
      the incidence of lung cancer, but results from 13 different studies now show an
      absence of any significant correlation between these parameters. In the case of
      CYP2E1, some studies indicate a relationship between lung cancer and the
      occurrence of a rare allele, although future research is needed in order to
      establish a significant relationship. It is concluded that, at the present stage,
      none of the polymorphic sites determined in the CYP genes can yet be used as
      markers for increased lung cancer risk. Future research in this field might be
      focused on the establishment of new polymorphic sites in the CYP genes, affecting
      inducibility or function, and on the molecular basis for the interesting
      differences in CYP1A1 inducibility.

PMID- 7620941
TI  - Genetic factors in individual responses to environmental exposures.
AB  - Individual susceptibility to lung cancer due to occupational and environmental
      exposures to carcinogenic agents has been shown to be modulated by host-specific
      factors. The underlying principle of these factors is the differences that confer
      sensitivity or resistance to the disease. Since the majority of chemical
      carcinogens are not capable of causing hazardous effects per se, the metabolism
      of these compounds is a crucial part of the initial host response to the
      environmental exposure. Disturbances in the balance between activation and
      detoxification may thus explain the individual variations in responses to
      exposures to carcinogens. Many of the metabolic enzymes have recently been shown
      to express genetic polymorphisms in the population, and an association has been
      found between cigarette smoke-induced lung cancer and CYP1A1, CYP2D6, and GSTM1
      genes. In addition, GSTM1 and NAT2 polymorphisms have been associated with
      susceptibility to bladder cancer. Since substantial ethnic differences exist in
      the distribution of altered and normal alleles, and findings in one ethnic group
      are not necessarily applicable to others, these biomarkers are still in the
      validation stage. However, as more information emerges on the specific features
      that lead to enhanced susceptibility they can undoubtedly be used to determine
      risks of environmental exposures to susceptible individuals and populations.

PMID- 7620942
TI  - DNA adducts in biomonitoring.
AB  - Application of methods to the measurement of DNA adducts in occupational and
      environmental studies was surveyed. The methods included the 32P-postlabeling
      assay, immunoassay, mass spectrometry, and synchronous fluorescence spectroscopy.
      Methods for detecting excreted urinary RNA and DNA adducts were also discussed.
      When the techniques have been applied in occupational settings with complex
      exposures, identification and quantitation of the adduct levels have not been
      possible. At present emphasis is being placed on the determination of specific
      adduct levels. This can often be achieved by adding a purification step before
      the determination of adducts. Inasmuch as humans differ in their metabolic
      capacity, it has become feasible to determine adducts in humans who are
      polymorphic in their xenobiotic metabolism.

PMID- 7620943
TI  - Polycyclic aromatic hydrocarbons: chemistry of DNA adduct formation.
AB  - Polycyclic aromatic hydrocarbon carcinogens are usually activated for DNA binding
      by the metabolic formation of bay region dihydrodiol epoxides with R,S,S,R
      stereochemistry. Such metabolites from planar hydrocarbons reacted preferentially
      with the amino groups of deoxyguanosine residues, whereas those from nonplanar
      hydrocarbons were more efficiently trapped by DNA and reacted preferentially with
      the amino groups of deoxyadenosine residues, in some cases. Molecular modeling
      and NMR measurements indicated that the conformations of DNA adducts depend upon
      the hydrocarbon involved and the cis or trans opening of the epoxide ring during
      adduct formation. The structural characterization of carcinogen-DNA adducts and
      investigations of relationships between specific adducts and biological effects
      represent an important background that can be valuable in molecular
      epidemiological approaches.

PMID- 7620944
TI  - Screening for p53 gene mutations in archived tumors of workers occupationally
      exposed to carcinogens: examples from analysis of bladder tumors.
AB  - Point mutations in the p53 tumor suppressor gene are the most common genetic
      alterations in human cancers. The nature and location of these mutations can be
      informative in assessing the importance of putative carcinogenic agents.
      Potential associations between a given carcinogen and a specific mutation pattern
      can be substantiated when the exposure history of the patients is known. While
      the past exposure to environmental risk factors is often difficult to determine,
      documented occupational exposure to carcinogens presents a unique situation for
      evaluating this approach. Analysis usually involves working with paraffin
      embedded tissues, fixed under conditions suboptimal for genetic analysis and
      stored for many years, since frozen tissues are not available in sufficient
      numbers. The particular methodological problems encountered with fixed samples
      are discussed here, using as illustration an ongoing study of oncogene and tumor
      suppressor gene mutations in archived bladder tumors of workers exposed to
      aromatic amines and nonexposed patients.

PMID- 7620945
TI  - p53 and ras gene mutations in lung cancer: implications for smoking and
      occupational exposures.
AB  - This paper reviews mutational activation of ras oncogenes and inactivation of the
      p53 tumor suppressor gene in human lung cancer. We discuss the frequency, type,
      and location of mutations in these genes in relation to known etiological factors
      for lung cancer. The most studied examples of these are exposure to tobacco
      smoke, and to radon and asbestos fibers at work. We summarize data from our
      laboratory on K-ras and p53 mutations in fresh tissue samples from patients with
      resected primary lung carcinoma whose smoking and occupational histories were
      known. Most of the tumors examined were histologically non-small cell carcinoma
      (NSCLC), mainly of the squamous cell carcinoma and adenocarcinoma types. We
      compare the prevalence and nature of mutations in the two histological types of
      NSCLC.

PMID- 7620947
TI  - On the use of molecular biology data in occupational and environmental
      epidemiology.
AB  - Major advances in molecular biology during recent years have helped to identify
      genes and enzymes that play an important role in many diseases. While not ruling
      out traditional forms of epidemiology, the application of epidemiologic study
      designs in molecular biological studies may provide possibilities of disclosing
      disease mechanisms at the gene level and identifying more specific indicators of
      disease. Data on adducts to DNA or protein usually lead to cross-sectional
      studies or cohorts. Genetically determined susceptibility or mutations in tumor
      cells might be available and possibly reflect etiologically important
      determinants. The case-control design is applicable and cost-effective for the
      analysis of such data.

PMID- 7620946
TI  - The molecular epidemiology of growth signal transduction proteins.
AB  - Cellular proteins involved in growth signal transduction pathways represent
      potential molecular epidemiologic biomarkers for various disease processes of
      toxicologic interest, particularly cancer. In many instances, the proteins gain
      access to the extracellular environment and thus can be detected in easily
      accessible biological fluids such as serum or plasma. This paper reviews the
      experience with selected examples of such proteins, including growth factors,
      growth factor receptors, G proteins, and nuclear DNA-binding proteins, as serum
      or plasma biomarkers of disease.

PMID- 7620948
TI  - Individual susceptibility and prevention of occupational diseases: scientific and
      ethical issues.
AB  - Genetic testing of employees is controversial; objections have been raised with
      regard to privacy, right to work, and the relevance of the tests. A study is
      being conducted on "the ethical, social, and scientific problems related to the
      application of genetic screening and genetic monitoring for employees in the
      context of a European approach to health and safety at work." A conceptual model
      is proposed of the complex interactions between exposure, acquired and inherited
      susceptibility, and risk for disease. The validity of tests for determining
      genotype and phenotype and their relevance for disease must be evaluated
      critically to provide an objective basis for ethical discussions. The
      acceptability of such tests is related to a number of issues, which are
      identified and discussed.

PMID- 7620949
TI  - Vascular surgery in Norway.

PMID- 7620950
TI  - The role of angioplasty to improve inflow for infrainguinal bypasses.

PMID- 7620951
TI  - Pharmacological prophylaxis against postoperative graft occlusion after
      peripheral vascular surgery: a world-wide survey.
AB  - OBJECTIVES: To define current practice regarding the use of pharmacological
      prophylaxis to prevent postoperative graft occlusion. DESIGN: Prospective open
      questionnaire. MATERIALS AND METHODS: Questionnaires regarding this subject were
      sent to vascular surgeons throughout the world to analyse current practice.
      RESULTS: 651 questionnaires were returned with a response rate of 62% and form
      the basis for this report. Data from 100,334 vascular reconstructions were
      reported in this survey. Prophylaxis against postoperative graft occlusions was
      common. Treatment periods were usually greater than 1 year. Among carotid surgery
      patients, 82% received prophylaxis, consisting mainly of low-dose acetysalicylic
      acid (ASA). In Mid-Europe the use of oral anticoagulation was more common than in
      other regions (p < 0.001). Among aneurysm surgery patients, 38% received
      prophylaxis. For infrainguinal bypass, ASA in low dose was the most commonly used
      agent worldwide. However, oral anticoagulation was more frequent in Mid-Europe,
      in contrast to South America where the combination of ASA and dipyridamole was
      most common. Considerable geographical differences regarding patient selection,
      the frequency of specific procedures and operative techniques existed.
      CONCLUSIONS: Important world-wide differences exist regarding prophylaxis for
      postoperative graft occlusion.

PMID- 7620952
TI  - Does the limb swell after revascularisation by percutaneous transluminal
      angioplasty?
AB  - OBJECTIVE: To discover if limb swelling occurs after successful revascularisation
      by percutaneous transluminal angioplasty (PTA). DESIGN: Prospective Study.
      SETTING: Vascular Laboratory. MATERIALS: Twenty-five patients with occlusive
      arterial disease of the lower limb revascularised by percutaneous transluminal
      angioplasty were studied. CHIEF OUTCOME MEASURES: The ankle/brachial pressure
      index and foot volumes measured by water displacement plethysmography were
      measured before and after PTA. MAIN RESULTS: The volume of the revascularised
      limb increased by 2% on the first day postangioplasty (p = 0.009) and 4% on the
      7th day (p < 0.001) compared with the contralateral leg. CONCLUSIONS: Leg
      swelling is a consequence of revascularisation of the ischaemic limb and occurs
      in the absence of damage to the lymphatic drainage of the limb.

PMID- 7620953
TI  - Lupus anticoagulant in patients with peripheral vascular disease: a prospective
      study.
AB  - OBJECTIVE: To assess the incidence of lupus anticoagulant (LAC) in patients with
      peripheral vascular disease. DESIGN: Prospective clinical study. SETTING:
      University Hospital. MATERIALS: 20 patients with claudication (group 2), 20
      patients with critical ischaemia (group 3) and 20 patients prior to elective
      abdominal aortic aneurysm surgery (group 4) were compared to 20 general surgical
      controls (group 1). CHIEF OUTCOME MEASURES: Venous blood samples for coagulation
      assay. MAIN RESULTS: Positive results for LAC by the Dilute Russell's viper venom
      time (DRVVT) with the platelet neutralisation procedure were present in 26 out of
      60 vascular patients compared with none of the 20 general surgical controls. The
      three vascular groups showed a similar prevalence of LAC and this differed
      significantly from that in the control group (chi 2 = 10.94, p = 0.0009). Of the
      26 positive results only three were associated with an abnormal activated partial
      thromboplastin time (APTT), which has previously been used as a marker for the
      presence of LAC activity. Fibrinogen levels were raised in seven of 20 patients
      in group 2 but were normal in the remaining vascular groups (p = 0.001). The mean
      factor VII level (124.1 units dl-1) in group 2 was higher than the mean of the
      remaining vascular patients (109.3 units dl-1, p < 0.05). CONCLUSIONS: The high
      prevalence of LAC in patients with peripheral vascular disease and the associated
      increased risk of early graft thrombosis may justify routine testing by DRVVT
      prior to reconstructive vascular surgery. Treatment of these patients with
      antiplatelet agents or formal anticoagulation perioperatively should be
      considered.

PMID- 7620954
TI  - Operative mortality and long-term relative survival of patients operated on for
      asymptomatic abdominal aortic aneurysm.
AB  - OBJECTIVE: Assessment of mortality and long-term relative survival following
      repair of asymptomatic abdominal aortic aneurysms. DESIGN: Retrospective review.
      SETTING: University Hospital. MATERIALS: Three hundred and twenty seven patients
      with a median age of 68 years and male to female proportion of 10:1. CHIEF
      OUTCOME MEASURES: Operative mortality and long-term mortality obtained from
      Norwegian Registrar's Office. Demographically matched expected survival
      calculated from death rate tables published by the Norwegian Central Bureau of
      Statistics. MAIN RESULTS: The overall operative mortality was 5.2%. Ten-year
      survival rate for all the patients was 38% compared to the expected of 52%. The
      standard mortality rate was 1.30, indicating a 30% higher mortality compared to a
      demographically matched population. Older patients and patients with known
      cardiac disease had significantly increased operative mortality. These patients
      also had the lowest long-term survival. Patients with cardiac disease suffered a
      postoperative mortality more than two times expected. CONCLUSIONS: Further
      studies are needed to define subgroups unsuitable for elective surgery.

PMID- 7620955
TI  - How successful is varicose vein surgery? A patient outcome study following
      varicose vein surgery using the SF-36 Health Assessment Questionnaire.
AB  - OBJECTIVE: Assessment of outcome after varicose vein surgery. DESIGN: Prospective
      study using the Health Assessment Questionnaire (SF36) which considers different
      aspects of overall health. SETTING: University Hospital and Community. MATERIALS:
      150 patients undergoing varicose vein surgery. CHIEF OUTCOME MEASURES: SF36
      questionnaires were sent pre-operatively and at 1 and 6 months post surgery. MAIN
      RESULTS: Eighty-nine (59%) patients answered all three questionnaires. Pre
      operatively their overall health was similar to that of the general population.
      The "cost" to the patient of the operation was demonstrated by an increased pain
      and reduced role function at 1 month post-operation (p < 0.01). By 6 months post
      operation, when compared with preoperative values, all dimensions except social
      function and health perception were improved (p < 0.01). Overall symptoms
      improved (p < 0.01) by 1 month and were further improved at 6 months.
      CONCLUSIONS: The general good health of varicose vein patients may justify the
      low priority given to their treatment, but the improvement in symptoms and
      general health that relatively simple surgery provides should ensure its
      continued provision as a health care service.

PMID- 7620956
TI  - Early experience with stretch polytetrafluoroethylene grafts for haemodialysis
      access surgery: results of a prospective randomised study.
AB  - OBJECTIVE: The purpose of this study was to evaluate the results and
      complications of standard ePTFE versus stretch ePTFE AV fistulas. DESIGN:
      Prospective randomised trial. SETTING: University Hospital. MATERIALS: During a 2
      year period 37 patients received 17 stretch and 20 standard ePTFE graft AV
      fistulas. CHIEF OUTCOME MEASURES: Patients were evaluated for the occurrence of
      complications and graft patency. Regular Duplex scans were performed to detect
      stenoses in the fistula circuit. MAIN RESULTS: Thrombotic events occurred in 40%
      of the standard ePTFE grafts, compared to 12% of the stretch ePTFE prostheses (p
      < 0.001). The incidence of puncture complications was similar in both groups. The
      cumulative primary patency rate in the stretch ePTFE group was significantly
      higher compared to the standard ePTFE group (1-year patency rates of 59% and 29%,
      respectively; p < 0.01). No differences in the duration of puncture site bleeding
      were observed. Duplex scanning showed a significantly greater number of stenoses
      in the standard ePTFE grafts. CONCLUSIONS: The new stretch ePTFE prosthesis has
      better primary patency rates and less stenoses due to intimal hyperplasia as
      compared to standard ePTFE grafts.

PMID- 7620957
TI  - Quality of life following infragenicular bypass and lower limb amputation.
AB  - AIMS: To objectively assess the quality of life after femorodistal bypass and
      compare this to quality of life achieved following primary limb amputation.
      DESIGN: Retrospective review. SETTING: Leicester Royal Infirmary, U.K., 1988
      1993. METHODS: A self-assessment postal questionnaire containing scales measuring
      emotional disorder, social functioning and mobility was sent to 112 patients who
      had previously undergone femorodistal bypass (n = 86) or primary limb amputation
      (n = 26). RESULTS: Further analysis demonstrated that a secondary procedure (PTA
      or graft revision) to maintain graft patency did not adversely affect quality of
      life. Additionally, patients undergoing secondary amputation after graft failure
      had an identical quality of life to those undergoing primary amputation.
      CONCLUSIONS: These data illustrate that the quality of life after successful
      femorodistal bypass is higher than after primary or secondary amputation. To
      attain the maximum quality of life in patients with critical ischaemia,
      femorodistal bypass should be performed wherever feasible.

PMID- 7620960
TI  - Effects of compression and type of bed surface on the microcirculation of the
      heel.
AB  - OBJECTIVE: To assess the effects of compression on the skin microcirculation of
      the heel using laser Doppler fluxmetry. DESIGN: Parallel groups comparing
      patients with control groups. SETTING: Department of Surgery, University College
      London Medical School, London. SUBJECTS AND MATERIALS: Ten patients at risk of
      developing pressure ulceration, 10 age- and sex-matched healthy subjects and 10
      young, healthy volunteers. An acrylic indenter with a slot to accommodate a laser
      Doppler probe was used to apply compression to the heel region. A pressure sensor
      was used to measure the applied compression. OUTCOME MEASURES: The resting laser
      Doppler flux was measured with the subject lying supine. Compression forces were
      then applied in increments from 50 g to 1500 g and the corresponding interface
      pressure (IP) and laser Doppler flux (LDF) recorded. The IP and LDF were also
      measured from the heel while the subject was lying on a low air-loss system and
      then on an NHS conventional hospital bed. RESULTS: The resting LDF is lower in
      the patient group compared to the control groups (p < 0.05). Compression of the
      heel caused a progressive decrease in LDF in all groups. Compression greater than
      50 mmHg as well as lying on an NHS bed reduced the LDF signal to a minimal value
      (biological zero). On the low air-loss system, the median LDF was 17% of the
      resting value in the age-matched control group and 32% in the patient group.
      CONCLUSIONS: The results indicate that the heel microcirculation is vulnerable to
      compression. The low air-loss system maintained the IP sufficiently low to
      prevent complete cessation of the heel microcirculation.

PMID- 7620959
TI  - Quantitative endoluminal measurements during angioscopy: an innovative technique.
AB  - AIM: To evaluate angioscopy in this Unit with respect to its application in lower
      limb vascular reconstructions. By providing magnified, colour images of the
      luminal surfaces of vein grafts, anastomoses and native arteries, angioscopy
      allows direct visualisation of imperfections and is sensitive in diagnosing
      technical problems. However, assessment is qualitative and magnification of the
      image can distort the operator's impression of true size. Angioscopy would be
      more versatile if it were possible to quantify the observed images. METHOD: A new
      technique has been developed to measure intra-luminal diameter from the
      angioscopic images. A linear displacement transducer is attached to the
      angioscope and accurately monitors its axial shift. Signals from the transducer
      are received by a personal computer equipped with a video frame grabber and
      analogue digital converter, together with appropriate software. The computer
      generates calculated dimensions based on geometrical principles, once each
      angioscope has been appropriately calibrated at the outset. RESULTS: Laboratory
      studies examining tubes of known dimensions have confirmed the reproducibility
      and accuracy of the technique. Simultaneous angioscopic and Duplex ultrasound
      measurements of the internal diameters of segments of vein suspended in a water
      bath were then carried out. Using the Duplex results as the 'gold standard',
      there was a strong correlation between the measurements obtained with the two
      techniques (Rs = 0.92). CONCLUSIONS: In the clinical context, this system has the
      capability to generate accurate endoluminal measurements during angioscopy. This
      has application for quality control in the selection of veins and inspection of
      run-off vessels during bypass grafting and in completion studies, following both
      operative and percutaneous procedures.

PMID- 7620958
TI  - Rifampicin impregnated Dacron grafts: no development of rifampicin resistance in
      an animal model.
AB  - AIM: Rifampicin impregnated Dacron grafts have been shown to be effective at
      preventing vascular graft infection in different animal models. The development
      of resistance to rifampicin would be a major drawback to the widespread use of
      such a graft. We aimed to determine how readily this would occur by using a sheep
      animal model. METHODS: Under general anaesthetic a 2cm long, 5mm diameter Dacron
      interposition graft inpregnated with 1.2 mg/ml rifampicin was placed in the left
      carotid artery. An extreme challenge of methicillin resistant Staphylococcus
      aureus (MRSA) using an inoculum of 10(9) colony forming units was placed directly
      onto the graft. The grafts were harvested at 3 weeks and cultures of the graft
      and tissues were taken. The presence or absence of any abscess formation,
      anastomotic disruption and graft thrombosis was noted. Any positive growths were
      identified and if found to be the same as the inoculum, the bacteria were used as
      the inoculum for another sheep. This was repeated once more. Thus we started with
      three sheep initially and used a total of nine sheep. RESULTS: There were no
      deaths. All grafts were infected with the same MRSA strain, confirmed on phage
      typing. There were three abscess and one anastomotic disruption. Seven of the
      grafts were occluded. The minimal inhibitory concentration (MIC) of the infecting
      inoculum and the bacteria retrieved were determined using the agar dilutional
      method. The MIC for the three initial inocula was < 0.007 mg/l. All subsequent
      strains isolated had an MIC of < 0.015 mg/l. This was a difference of one
      dilution and not significant. CONCLUSION: There was no development of rifampicin
      resistance using this animal model.

PMID- 7620961
TI  - Attachment, replication and thrombogenicity of genetically modified endothelial
      cells.
AB  - Endothelial cell seeding of prosthetic surfaces has been proposed as a technique
      to improve the patency of vascular grafts following arterial reconstruction. The
      introduction of specific recombinant DNA into seeded endothelial cells may
      enhance the anti-thrombogenic nature of the endothelial-blood interface with a
      consequent reduction in graft thrombosis. However, the successful use of
      genetically modified endothelial cells in the seeding process relies on the cells
      retaining normal function in terms of cellular replication, attachment and
      secretion of anti-thrombotic mediators. Successful genetic manipulation of human
      endothelial cells has been accomplished by viral and chemical methods. AIM: To
      study the functional characteristics of electrontransfected endothelial cells.
      METHODS AND RESULTS: Endothelial cells were electro-transfected with the test
      plasmid pTCF at a transfection efficiency of 10% utilising a single electric
      pulse with an electric field of 1000 volts/cm and a time constant of 12.8ms. The
      functional status of transfected endothelial cells was then compared with a
      control endothelial cell population. There were no significant differences in
      replication (p = 0.76), attachment (p = 0.43), basal (p = 0.89) or stimulated (p
      = 0.11) prostacyclin release between transfected cells as compared with control
      endothelial cells. CONCLUSIONS: Genetically modified cells are functionally
      normal, and may be used in endothelial cell seeding of prosthetic vascular
      surfaces.

PMID- 7620963
TI  - Labile blood pressure after bilateral carotid body tumour surgery.

PMID- 7620962
TI  - Infrapopliteal percutaneous transluminal angioplasty: a safe and successful
      procedure.
AB  - AIM: To review outcome of 40 consecutive infrapopliteal percutaneous transluminal
      angioplasty (PTA) procedures performed over a 65 month period. CHIEF OUTCOME
      MEASURES: The indication for PTA was intermittent claudication in 20 (50%) cases
      and rest pain, ulceration or gangrene in the remainder. RESULTS: There was one
      technical failure; the remaining 39 limbs were all clinically improved by 24 h
      and this improvement was maintained at 3 months in 36 (90%). There were no deaths
      nor limb loss related to PTA and 2 embolic complications were successfully
      treated percutaneously. The primary and secondary symptomatic patencies at 24
      months were 59 and 79% respectively. The actuarial limb salvage rate at 1 year
      for the 20 limbs presenting with critical ischaemia was 77%, and 10 of the 14
      procedures performed for ulceration or gangrene resulted in healing with only
      minor surgical intervention. CONCLUSIONS: With modern endovascular techniques,
      infrapopliteal PTA is a safe, worthwhile and durable procedure.

PMID- 7620964
TI  - Infected false aneurysm following carotid endarterectomy with PTFE angioplasty.

PMID- 7620965
TI  - Vein patch rupture after carotid endarterectomy.

PMID- 7620966
TI  - Atypical aorto-enteric fistula.

PMID- 7620967
TI  - Single-stage vascular surgery for a ruptured inflammatory abdominal aortic
      aneurysm associated with septicaemia.

PMID- 7620968
TI  - DVT diagnosis.

PMID- 7620969
TI  - Accelerated peripheral arterial thrombolysis using pulse-spray thrombolysis (PST)

PMID- 7620970
TI  - LMWH in vein grafts.

PMID- 7620971
TI  - Xenopus oocytes as a heterologous expression system for plant proteins.
AB  - The Xenopus oocyte is a robust and convenient system for the transient expression
      of many different animal proteins and it has recently been demonstrated that
      oocytes can also translate, process, and target plant proteins. This expression
      system can also be used to clone genes, characterize function, and study
      posttranslational processing of proteins. Here we describe the methodology for
      the expression of plant proteins, in particular membrane proteins, in Xenopus
      oocytes.

PMID- 7620973
TI  - Selection of primers for polymerase chain reaction.
AB  - One of the most important factors affecting the quality of PCR is the choice of
      primers. In general, the longer the PCR product the more difficult it is to
      select efficient primers and set appropriate designing primers, and in general,
      the more DNA sequence information is available, the better the chance of finding
      an optimal primer pair. Efficient primers can be designed by avoiding the
      following flaws: primer-dimer formation, self-complementarity, too low Tm of the
      primers, and/or their incorrect internal stability profile. Tips on subcloning
      PCR products, calculating duplex stability (predicting dimer formation strength),
      and designing degenerate primers are given.

PMID- 7620974
TI  - Purification and cloning of DNA fragments fractionated on agarose gels.
AB  - Purification of DNA fragments from acrylamide or agarose gels is a commonly used
      technique in the molecular biology laboratory. This article describes a rapid,
      efficient, and inexpensive method of purifying DNA fractions from an agarose gel.
      The purified DNA is suitable for use in a wide range of applications including
      ligation using DNA ligase. The procedure uses standard high-melting-temperature
      agarose and normal TBE electrophoresis buffer. In addition, the protocol does not
      involve the use of highly toxic organic solvents such as phenol.

PMID- 7620972
TI  - Irradiation and fusion gene transfer.
AB  - Irradiation and fusion gene transfer (IFGT) is a technique that spans the gap
      between the limitations of molecular methods and somatic-cell genetics, allowing
      the separation of DNA fragments between 0.25 and 30 Mb in size. In conjunction
      with genetic linkage analysis and physical mapping techniques, IFGT provides a
      very useful addition to methods for cloning disease loci, and mapping chromosomes
      and entire genomes.

PMID- 7620978
TI  - Perspectives in protein engineering and complementary technologies, Oxford, UK,
      September 13-17, 1994. To design or select: that is the question.

PMID- 7620975
TI  - The biotechnology and applications of antibody engineering.
AB  - The exquisite specificity of monoclonal antibodies (MAb) has long provided the
      potential for creating new reagents for the in vivo delivery of therapeutic drugs
      or toxins to defined cellular target sites or improved methods of diagnosis.
      However, many difficulties associated with their production, affinity,
      specificity, and use in vivo have largely confined their application to research
      or in vitro diagnostics. This situation is beginning to change with the recent
      developments in the applied molecular techniques that allow the engineering of
      the genes that encode antibodies rather than the manipulation of the intact
      antibodies themselves. Techniques, such as the polymerase chain reaction, have
      provided essential methods with which to generate and modify the genetic
      constituents of antibodies, allow their conjugation to toxins or drugs, provide
      ways of humanizing murine antibodies, and allow discrete modular antigen binding
      components to be produced. More recent developments of in vitro expression
      systems and powerful phage surface display technologies will without doubt play a
      major role in future antibody engineering and in the successful development of
      new diagnostic and therapeutic antibody-based reagents.

PMID- 7620977
TI  - Increased reliability of selective PCR by using additionally mutated primers and
      a commercial Taq DNA polymerase enhancer.
AB  - A reliable selective PCR procedure that combines the use of additionally mutated
      primers with the specificity-enhancing properties of a commercial preparation
      (Perfect Match, Stratagene) is described. The human immunodeficiency virus type 1
      pol gene point mutations known to confer in vitro resistance to azidothymidine
      were examined as a model for optimization of the assay. The usual strategy of
      deliberately introducing an additional mismatch 1 residue from the 3' end in the
      wild-type and mutant primers did not allow reproducible discrimination between
      wild-type and mutant target sequences. Addition of minimal amounts of Perfect
      Match to the same PCR mixtures resulted in a significantly enlarged range of
      selective annealing temperatures, providing a valuable and cost-effective means
      for reliable detection of known mutations by selective PCR.

PMID- 7620976
TI  - RNA viruses as vectors for the expression of heterologous proteins.
AB  - RNA viruses comprise a wide variety of infectious agents, some of which are the
      cause of disease in humans, animals, and plants. Recombinant DNA technology is
      now making it feasible to modify these genomes and engineer them to express
      heterologous proteins. Several different schemes are being employed that depend
      on the genome organization of the virus and on the strategy of replication of the
      particular virus. Several different examples are illustrated and potential uses
      as well as possible problems are discussed. In the future reverse genetics may
      convert some of these viruses from agents of disease to agents of cure.

PMID- 7620979
TI  - Rapid transfer of low copy-number episomal plasmids from Saccharomyces cerevisiae
      to Escherichia coli by electroporation.
AB  - A simple and reproducible method for transferring low copy-number episomal
      plasmids from yeast to Escherichia coli has been developed. Although slightly
      more time-consuming than direct transfer methods, which are effective with high
      copy number plasmids, the method is significantly faster than methods that
      require purification of yeast DNA. Plasmid DNA is released from yeast cells
      during brief treatments involving grinding with glass beads and heating. The
      treated yeast are cooled, electrocompetent E. coli is added, the mixture is
      electroporated, and transformants are selected using standard conditions for E.
      coli electrotransformation. The procedure typically yields sufficient
      transformants for most applications.

PMID- 7620980
TI  - Rapid identification of polymorphic CA-repeats in YAC clones.
AB  - Positional cloning of rare disease genes depends on the availability of highly
      polymorphic markers near the disease loci. The most abundant class of polymorphic
      markers in the human genome is CA-repeats. We have developed a strategy for the
      rapid isolation of highly polymorphic CA-repeats from YAC clones. Total DNA of
      yeast clones containing partly overlapping YACs is digested with frequent cutter
      restriction enzymes, blotted and hybridized with a poly(CA/GT) probe under high
      stringency conditions that enable preferential detection of long CA-repeats. The
      repeats detected in this way are isolated by PCR using vectorette linkers,
      sequenced, and appropriate flanking markers are constructed for genotyping. All
      of the CA-repeats identified using this approach were highly polymorphic. This
      simple and rapid approach should allow the development of highly polymorphic
      markers at any genomic region cloned in YACs.

PMID- 7620982
TI  - Correcting sequencing errors in DNA coding regions using a dynamic programming
      approach.
AB  - This paper presents an algorithm for detecting and 'correcting' sequencing errors
      that occur in DNA coding regions. The types of sequencing errors addressed are
      insertions and deletions (indels) of DNA bases. The goal is to provide a
      capability which makes single-pass or low-redundancy sequence data more
      informative, reducing the need for high-redundancy sequencing for gene
      identification and characterization purposes. This would permit improved
      sequencing efficiency and reduce genome sequencing costs. The algorithm detects
      sequencing errors by discovering changes in the statistically preferred reading
      frame within a putative coding region and then inserts a number of 'neutral'
      bases at a perceived reading frame transition point to make the putative exon
      candidate frame consistent. We have implemented the algorithm as a front-end
      subsystem of the GRAIL DNA sequence analysis system to construct a version which
      is very error tolerant and also intend to use this as a testbed for further
      development of sequencing error-correction technology. Preliminary test results
      have shown the usefulness of this algorithm and also exhibited some of its
      weakness, providing possible directions for further improvement. On a test set
      consisting of 68 human DNA sequences with 1% randomly generated indels in coding
      regions, the algorithm detected and corrected 76% of the indels. The average
      distance between the position of an indel and the predicted one was 9.4 bases.
      With this subsystem in place, GRAIL correctly predicted 89% of the coding
      messages with 10% false message on the 'corrected' sequences, compared to 69%
      correctly predicted coding messages and 11% falsely predicted messages on the
      'corrupted' sequences using standard GRAIL II method (version 1.2).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7620981
TI  - PCR-mediated recombination and mutagenesis. SOEing together tailor-made genes.
AB  - Gene Splicing by Overlap Extension (gene SOEing) is a sequence-independent method
      for site-directed mutagenesis and/or recombination of DNA molecules. It is based
      on the idea that a PCR product can be engineered by adding or changing sequences
      at its ends so that the product can itself be used to prime DNA synthesis in a
      subsequent overlap-extension reaction to create mutant or recombinant molecules.
      As the engineered genes are created in vitro without reliance on host organisms
      or restriction sites, gene SOEing provides a powerful and versatile tool for
      genetic investigation and engineering.

PMID- 7620983
TI  - Prediction of zinc finger DNA binding protein.
AB  - Using the neural network algorithm with back-propagation training procedure, we
      analysed the zinc finger DNA binding protein sequences. We incorporated the
      characteristic patterns around the zinc finger motifs TFIIIA type (Cys-X2-5-Cys
      X12-13-His-X2-5-His) and the steroid hormone receptor type (Cys-X2-5-Cys-X12-15
      Cys-X2-5-Cys-X15-16-Cys-X4-5-Cys-X8-10- Cys-X2-3-Cys) in the neural network
      algorithm. The patterns used in the neural network were the amino acid pattern,
      the electric charge and polarity pattern, the side-chain chemical property and
      subproperty patterns, the hydrophobicity and hydrophilicity patterns and the
      secondary structure propensity pattern. Two consecutive patterns were also
      considered. Each pattern was incorporated in the single layer perceptron
      algorithm and the combinations of patterns were considered in the two-layer
      perceptron algorithm. As for the TFIIIA type zinc finger DNA binding motifs, the
      prediction results of the two-layer perceptron algorithm reached up to 96.9%
      discrimination, and the prediction results of the discriminant analysis using the
      combination of several characters reached up to 97.0%. As for the steroid hormone
      receptor type zinc finger, the prediction results of neural network algorithm and
      the discriminant analyses reached up to 96.0%.

PMID- 7620984
TI  - Calculation of the photoperiod length.
AB  - This paper describes an algorithm for calculating the photoperiod length
      (daylength as intercepted by plants) with special emphasis on its use in models
      describing plant growth and development. The ability to calculate simply and
      exactly the length of the day for different locations is essential not only for
      the models describing photoperiodic effects on plant development but also for the
      simulation of the daily sum of the produced photosynthates or the calculation of
      the average daily temperature. Two previously published algorithms for
      calculation of photoperiod length were compared with ours, based on the system of
      equations describing movement of earth around the sun. The curve gained when
      plotting daylengths calculated by our algorithm against a particular date is
      asymmetrical with respect to daylength in equinoxes, while the curve showing the
      data calculated by both compared algorithms is apparently symmetrical. The
      differences between our algorithm and the other two algorithms increase with
      increasing latitude: at 50 degrees N they are in the range of 6.9-13.8 min. We
      have also demonstrated an effect of location height, geographical longitude and a
      year on calculated daylength of a particular day.

PMID- 7620985
TI  - PBM: a software package to create, display and manipulate interactively models of
      small molecules and proteins on IBM-compatible PCs.
AB  - The PBM package was developed to create, display and conveniently manipulate
      protein and small molecule structures on IBM-compatible microcomputers. It
      consists of four modules: CREATE, SPHERE, RIBBON and CONVERT. CREATE includes
      commands to create or alter ('mutate') the primary and subsequently the tertiary
      structure of a given peptide or protein by defining phi and psi angles of
      residues at will, options to add, delete or alter atoms in a structure, utilities
      to choose easily between the most common rotamers of amino acid residue
      sidechains and options to analyse in various ways a protein conformation. SPHERE
      provides for an interactive manipulation of structures containing up to 2700
      atoms which can belong up to six different molecules. All manipulations can be
      made with the use of an ordinary mouse, by choosing from a variety of pull-down
      menus. Three types of models can be implemented to display molecules on the
      computer screen or the plotter: skeletal, solid space-filling and wireframe space
      filling models. RIBBON creates ribbon models of proteins and allows for a limited
      variety of interactive manipulations. CONVERT is a file converter, which is
      capable of converting files of atom coordinates of literally any format to
      Brookhaven Data Bank format files. The package produces very good results for
      protein molecules of reasonable sizes, both in terms of graphics quality and
      speed of operations, on an 80486 IBM PC-compatible machine equipped with a 1
      MByte VGA display card and a colour VGA monitor, which is a recommended
      configuration.

PMID- 7620986
TI  - A local alignment tool for very long DNA sequences.
AB  - This paper presents a practical program, called sim2, for building local
      alignments of two sequences, each of which may be hundreds of kilobases long.
      sim2 first constructs n best non-intersecting chains of 'fragments', such as all
      occurrences of identical 5-tuples in each of two DNA sequences, for any specified
      n > or = 1. Each chain is then refined by delivering an optimal alignment in a
      region delimited by the chain. sim2 requires only space proportional to the size
      of the input sequences and the output alignments, and the same source code runs
      on Unix machines, on Macintoshes, on PCs, and on DEC Alpha PCs. We also describe
      an application of sim2 for aligning long DNA sequences from Escherichia coli.
      sim2 facilitates contig-building by providing a complete view of the related
      sequences, so differences can be analyzed and inconsistencies resolved. Examples
      are shown using the alignment display and editing functions from the software
      tool ChromoScope.

PMID- 7620987
TI  - BULLET: a computer simulation of shotgun DNA sequencing.
AB  - BULLET is a computer program that simulates shotgun sequencing of DNA. The
      program has been used to simulate the sequencing of DNA fragments from 2 to 30
      kb. To obtain 80% single or double-stranded sequence, a doubling of the DNA
      fragment size necessitates twice the number of sequencing reactions. However, a
      similar linear relationship does not apply to the determination of 100% single or
      double-stranded sequence. Data from BULLET were used to derive simple linear
      formulae that estimate the number of sequencing reactions necessary to partially
      sequence a fragment of DNA irrespective of size. When 80% of the double-stranded
      sequence has been determined, approximately 98% of single-stranded sequence will
      be known. This is a reasonable point to change to a more directed strategy of DNA
      sequencing.

PMID- 7620988
TI  - A comprehensive representation of extensive similarity linkage between large
      numbers of proteins.
AB  - A method is described for the representation of a bird's-eye view of similarity
      relationships between large numbers of proteins. With the aid of single-linkage
      clustering, proteins are clustered into groups on the basis of various types of
      similarity such as sequence similarity estimated between all the protein pairs.
      Proteins in a group are directly or indirectly connected to all proteins in the
      same group by similarities higher than a given threshold and show no similarity
      higher than the threshold to any proteins outside the group. Thus, all the
      proteins directly or indirectly related to a protein can be selected out of a
      large number of proteins by the clustering. Recursion of this clustering of
      proteins in each group leads to further classification of the proteins. The
      similarity relationships in each group are visually represented by a similarity
      matrix. This representation has the advantage of easy detection of the existence
      of multidomain proteins and diverged families as well as closely related
      proteins. Such as exhaustive approach to similarity relationships of proteins
      will be useful for revealing functional/structural/evolutionary units in
      proteins.

PMID- 7620989
TI  - Phylogeny inferred from codon usage pattern in 31 organisms.
AB  - We employed the Codonusage database to analyze the codon usage pattern in 31
      organisms from all the main biological taxa. We tested the similarity in codon
      usage pattern between each organism and all the others by the Pearson linear
      correlation coefficient. The 465 values obtained were located in a 31 x 31
      triangular matrix from which a correlation distance matrix was calculated. An
      evolutionary dendrogram was then constructed from these distances. The results
      showed a fair correlation between codon usage patterns and phylogenetic
      relationships, at least for organisms which diverged in rather recent times (end
      of Jurassic--beginning of Cretaceous).

PMID- 7620990
TI  - TRAMP: a software package for generating transposon maps.
AB  - TRAMP is a software package for generating transposon maps that are used for DNA
      sequencing. The package provides a variety of automated tools that can always be
      overridden by the user. The central part of the package is its selection
      algorithm that finds the most robust map with the smallest number of inserts.
      TRAMP has been in daily use by the sequencing team at LBL since it was introduced
      in the Spring of 1994. It is applicable to any sequencing project utilizing the
      directed strategy.

PMID- 7620991
TI  - Introducing variable gap penalties to sequence alignment in linear space.
AB  - The problem of finding an optimal sequence alignment has been solved by
      Hirschberg (1975) in quadratic time and linear space. Myers and Miller (1988)
      presented an implementation of this algorithm for aligning biological sequences,
      incorporating affine gap penalties. The algorithm, has been essential in allowing
      progressive multiple sequence alignments to be performed on microcomputers with
      limited memory capacity. This paper presents a further development of the Myers
      and Miller algorithm. Here, we maximize similarity scores and, more
      significantly, introduce position-specific gap penalties. Thus, residue-dependent
      information such as structure preferences and existing gaps in a partial
      alignment can be applied to the solution of the alignment problem.

PMID- 7620992
TI  - Accurate determination of DNA in agarose gels using the novel algorithm
      GelScann(1.0).
AB  - GelScann(1.0) is a user-friendly program that accurately quantitates DNA from CCD
      imaged agarose gels. The algorithm automatically locates lanes, locates bands
      within a given lane, and quantitates the intensity of each band. GelScann (1.0)
      uses a statistical method to discriminate DNA from local background fluorescence.
      The sensitivity of the LaneFinder and BandFinder can be adjusted by the user
      interacting with GelScann (1.0)'s option box. We demonstrate that GelScann(1.0)
      can accurately determine DNA that GelScann(1.0) can accurately determine DNA
      concentrations for routine molecular biology applications and determine the
      relative intensities of PCR amplified fragments for genetic testing.

PMID- 7620993
TI  - Middle-range clustering of nucleotides in genomes.
AB  - We propose a novel, transparent and very simple algorithm to analyze middle-range
      correlations in genomic nucleotide sequences. Analysis by this algorithm of the
      EMBL Nucleotide Sequence Database demonstrates that all four nucleotides cluster
      in the genomic nucleotide sequences of eukaryotes on the scale of several hundred
      base pairs. In prokaryotes, the clustering is weak but still evident. The non
      dominant three bases are deficient in the clusters, while A is the most deficient
      nucleotide in the clusters of C, and vice versa, and G is the most deficient
      nucleotide in the clusters of T, and vice versa. The algorithm also detects CG
      islands, extending over 1 kb, in vertebrate sequences. In plants, the CG islands
      are shown to be much smaller, if they exist at all. A clustering tendency is also
      exhibited by the TA doublet. Other doublets do not cluster. We observe no strong
      correlation between nucleotides separated in genomes by > 1 kb.

PMID- 7620994
TI  - MIST: a user-friendly metabolic simulator.
AB  - The Metabolic Interactive Simulation Tool, MIST, is a software package, running
      under Microsoft Windows 3.1, which can be used for dynamic simulations,
      stoichiometric calculations and control analysis of metabolic pathways. The
      pathways can be of any complexity and are defined by the user in a simple,
      interactive way. The user-defined enzymatic rate equations can be compiled either
      by an external or an internal compiler. Simulations of pathways compiled by an
      external compiler run significantly faster, but since these compilers are
      commercial software, they are not distributed together with MIST. The simulations
      are performed by numerical integration of a set of ordinary differential
      equations. The integration can be done by either an explicit fourth-order Runge
      Kutta algorithm or a semi-implicit third-order Runge-Kutta algorithm, both with
      adjustable step size. The second algorithm can be used if the set of differential
      equations is stiff. Vector-based drawing facilities are included in the program,
      with which results can be presented in graphs. Results of simulations, including
      graphics, can be stored in files. MIST is a very user-friendly, flexible and yet
      powerful program, with the mathematical details regarding models, simulations and
      calculations hidden from the user. This makes it suitable for scientists and
      students with limited computer experience.

PMID- 7620995
TI  - A handy database for culture collections worldwide: CCINFO-PC.
AB  - Culture collections are reservoirs of cultivable microbes, cell lines and gene
      libraries. Their role and duty are to supply biological resources to biomedical
      communities; nevertheless, their visibility from the public is low because most
      culture collections still have poor accesses via the Internet. Therefore the WFCC
      World Data Center on Micro-organisms (WDCM) developed a database that runs on IBM
      PCs and compatibles, which are the most popular computer and will be as powerful
      as workstations. The database includes various information: activities of 484
      culture collections from 58 countries; an integrated list of their holdings of
      bacteria, fungi and yeast; and data entry system for culture collections.

PMID- 7620996
TI  - A compression mechanism for sequence databases to improve the efficiency of
      conventional tools.
AB  - This paper describes a method to compress molecular biology databases that are
      characterized by an increasing proportion of data derived from genome projects.
      The performance of our tool has been tested on various data files of the EMBL
      nucleotide sequence database. The best compression ratios were achieved on EST
      (Expressed Sequence Tags) data, typically derived from large-scale sequence
      projects. The compression of sequence database updates was tested in combination
      with the common Unix compression program 'compress'. Our tool improved the
      efficiency of 'compress' on average by 16%.

PMID- 7620997
TI  - Optimal production of biological documentation: the JAM format.
AB  - The current environment for providing documentation for users in molecular
      biology frequently requires written information for both printed and electronic
      media. The JAM. (Just Another Metafile) Format requires that only a single file
      of text is written. This is, then, processed by the jam program which converts
      this text to a document set which is suitable for on-line documentation in the
      hypertext mark-up language (HTML) of the World Wide Web system. For printed
      output, the jam program can produce either text in wordprocessor-ready Rich Text
      Format (RTF), or source code for the LaTEX typesetting system. The latter allows
      for professional text layout and can generate, amongst other formats, postscript
      files to be printed on a variety of devices.

PMID- 7620998
TI  - The use of 13-cis-retinoic acid in the treatment of oral leukoplakia: short-term
      observations.

PMID- 7620999
TI  - Condylar resorption in orthognathic surgery.

PMID- 7621000
TI  - Transverse root fracture treatment.

PMID- 7621001
TI  - Oral lichen planus and chronic liver disease.

PMID- 7621002
TI  - Submental approach to oroendotracheal intubation in patients with midfacial
      fractures.
AB  - A submental endotracheal intubation technique is an alternative to
      nasoendotracheal intubation and tracheostomy in the management of patients with
      severe midfacial fractures. The procedure is simple to do and has a low
      morbidity.

PMID- 7621003
TI  - Disk displacement and temporomandibular joint symptoms in orthognathic surgery
      patients.
AB  - The purpose of this study was to document the prevalence of disk displacement and
      temporomandibular joint symptoms in orthognathic surgery patients. Fifty-three
      consecutive patients with different types of dentofacial anomalies were examined
      clinically and with bilateral arthrography. Disk displacement unilaterally or
      bilaterally was found in 57% of the patients or 46% of the joints. Displacement
      with reduction was seen in 38 joints, and displacement without reduction was seen
      in 11 joints. Fifty-three percent of the patients had pain in the
      temporomandibular joint or masticatory muscles, 30% of the joints demonstrated
      clicking, and 4% had crepitation. No association was found between disk
      displacement and clinical symptoms except for an association between clicking and
      anterior disk displacement with reduction. Neither could an association between
      disk displacement and the type of dentofacial anomaly be appreciated. It was
      concluded that disk displacement was frequent in patients with dentofacial
      anomalies, but no relationship to temporomandibular joint symptoms and the type
      of dentofacial anomaly could be clearly demonstrated.

PMID- 7621004
TI  - Calcium pyrophosphate dihydrate deposition disease of the temporomandibular
      joint. A case report and review of the literature.
AB  - An asymptomatic preauricular swelling in a 58-year-old man appeared as a parotid
      mass and was diagnosed as calcium pyrophosphate dihydrate crystal deposition
      disease of the temporomandibular joint. This article describes the diagnostic
      criteria and management of this rare condition and reviews the 13 cases that have
      been reported to date.

PMID- 7621005
TI  - Effect of age and radiation on bone healing adjacent to hydroxyapatite placed in
      the tibia of rats.
AB  - This study investigated the effect of age and radiation on healing after
      implantation of hydroxyapatite granule in bone. Two groups of 16 male Wistar
      rats, aged 4 weeks and 2 years were used for this study. Hydroxyapatite particles
      were placed into the tibia 28 days after the delivery of 15 Gy of irradiation
      from a Linac source. The results of the present study suggest that an old rat was
      more vulnerable to the radiation than a young rat. It seemed that age might also
      be an important factor in the prognosis of the implanted hydroxyapatite in
      irradiated bone.

PMID- 7621006
TI  - Early diagnosis of multiple hamartoma and neoplasia syndrome (Cowden disease).
      The role of the dentist.
AB  - A typical case of Cowden disease is presented. This is rare mucocutaneous
      disease, genetically determined, with multiple organ system involvement in which
      a malignancy, particularly of breast and thyroid gland, may develop. The disease
      can be diagnosed in its early stages by gingival and cutaneous manifestations. We
      emphasize that the dentist may be the first health care professional who
      recognizes the syndrome, which is a crucial step to prevent and cure the
      predictable malignancy.

PMID- 7621007
TI  - Clinical assessment of gingival size among patients treated with diltiazem.
AB  - Gingival overgrowth induced by nifedipine has been extensively reported. This
      finding, however, does not apply to gingival size changes caused by other calcium
      antagonists such as diltiazem. We studied the gingiva of 13 subjects with
      ischemic cardiopathy who had been treated with diltiazem and established two
      control groups: (1) a healthy group of 12 patients and (2) a group of 10 patients
      with ischemic cardiopathy and concomitant treatment similar to that applied to
      the diltiazem group except that they had not been administered any type of
      calcium antagonists. The size of the gingiva around the six anterior teeth was
      measured on plaster models of the upper and lower jaws. Significantly higher
      scores of the size of the gingiva were found when patients treated with diltiazem
      were compared with the patients in the other two groups (p < 0.05) gingiva were
      found when patients treated with diltiazem were compared with the patients in the
      other two groups (p < 0.05) and also when interproximal (p < 0.05) and vestibular
      (p < 0.05) sites were considered. We did not observe any significant difference
      in the plaque index of each group (p < 0.05); only bleeding after probing was
      found statistically different between the diltiazem and the nondiltiazem groups.

PMID- 7621008
TI  - Quantitative assessment of dysphagia in patients with primary and secondary
      Sjogren's syndrome.
AB  - Dysphagia is a common complaint from patients with salivary gland dysfunction.
      The purpose of this study was to assess and compare dysphagia in two patient
      groups with salivary gland dysfunction (primary Sjorgen's syndrome and secondary
      Sjogren's syndrome with systemic lupus erythematosus, and a matched control
      group. Subjects diagnosed with primary Sjogren's syndrome (n = 13) and secondary
      Sjogren's syndrome with systemic lupus erythematosus (n = 15) were selected for
      the study. An age- and sex-matched group of control subjects (n = 14) was
      selected for comparison. Dysphagia assessments, including videofluoroscopy were
      performed. Dysphagia was quantified clinically and videofluoroscopically by
      measurement of 10 seconds of basal or dry swallows as compared with 10-second 10
      ml water bolus swallows in all subjects. Subjective evaluations were recorded on
      a calibrated 10-cm visual analog scale. The results indicated a significant
      difference in the dry swallows as compared with the water bolus swallows for both
      salivary gland dysfunction groups and for both dry swallows and water bolus
      swallows as compared to controls. Videofluoroscopy yielded significantly
      prolonged pharyngeal transit times in both salivary gland dysfunction groups as
      compared with control. Subjective results indicated a greater degree of dysphagia
      symptoms in both the salivary gland dysfunction groups (p < 0.001). Conclusions
      from this study indicate clinically significant dysphagia in patients with
      salivary gland dysfunction associated with Sjogren's syndrome compared with a
      control population.

PMID- 7621010
TI  - Oral epithelial dysplasia and the development of invasive squamous cell
      carcinoma.
AB  - Oral epithelial dysplasia, the histopathologic marker of a premalignant disorder
      of the mouth mucosa, may present clinically as leukoplakia, erythroplakia, or
      leukoerythroplakia. Its presence in lesions of the oral mucosa is predictive by a
      variable rate (6.6% to 36%) of transformation to invasive squamous cell
      carcinoma. We studied the clinical features and microscopic slides of 308 case of
      oral epithelial dysplasia in our biopsy service and retrospectively evaluated 44
      of these with follow-up data for transformation to invasive squamous cell
      carcinoma. Forty-four patients had follow-up of more than 6 months with a mean
      follow-up time of 18.4 months. Twenty (45%) were clinically free of disease and
      15 (34%) had recurrence of the dysplasia. An additional two cases of lower grades
      of the disease recurred as carcinoma in situ. Invasive squamous cell carcinoma
      developed in seven (16%) in a mean transformation time of 33.6 months.

PMID- 7621009
TI  - Mineralization of Streptococcus mutans in vitro. An ultrastructural study.
AB  - Streptococcus mutans mineralization was studied in vitro, with the use of various
      metastable calcium phosphate solutions, fluoride-containing or otherwise.
      Degeneration of bacteria always occurred before their mineralization. After
      complete mineralization of the cytoplasmic area, growth of crystals was observed
      both in length and in thickness within the extracellular environment. Composition
      of the calcifying medium was an essential factor in the S. mutans mineralization
      process. The present study shows that, contrary to carbonate and magnesium ions
      that prevent intra- and extracellular deposits, fluoride ions promote crystal
      growth in the above mentioned mediums. Clinical implications of the role of
      fluoride, at the plaque level, are foreseen.

PMID- 7621011
TI  - Basal cell adenocarcinoma of the submandibular gland.
AB  - Basal cell adenoma is a well recognized histopathologic variant of monomorphic
      adenoma of salivary gland, but in recent years there have been occasional reports
      of malignant basal cell tumors of major salivary glands. We present a case report
      of one such basal cell adenocarcinoma arising in the submandibular gland and
      discuss the differential diagnosis and distinction from a basal cell adenoma. We
      also review the published literature on basal cell adenocarcinoma. This is the
      first case of basal cell adenocarcinoma to be studied in detail by both
      immunohistochemistry and electron microscopy. There has been debate in the past
      as to the cell of origin of salivary gland basal cell tumors and specifically as
      to whether myoepithelial differentiation occurs in these tumors. The
      immunohistochemical and ultrastructural features of this case provide evidence
      for a dual population of ductal and myoepithelial cells. A flow cytometric
      analysis of nuclear deoxyribonucleic acid content showed the presence of DNA
      aneuploidy within one tissue block.

PMID- 7621012
TI  - Histologic evaluation of tetracalcium phosphate-based cement as a direct pulp
      capping agent.
AB  - Histologic healing processes were observed at 1, 3, 7, and 10 days after
      application with either tetracalcium phosphate cement or calcium hydroxide cement
      to the exposed pulp of the rat maxillary incisors. In teeth applied with calcium
      hydroxide cement, necrotic tissue was present beneath the cement before new hard
      tissue formed. In contrast, tetracalcium phosphate cement elicited a dentine
      bridge formation with no evidence of either intervening tissue necrosis or marked
      inflammation. Furthermore on ultrastructural examination the newly formed hard
      tissue was in direct contact with the material. This study suggests that 4CP
      cement possesses a biocompatible property, which indicates its potential for use
      as a direct pulp-capping agent.

PMID- 7621013
TI  - Endodontic cements induce alterations in the cell cycle of in vitro cultured
      osteoblasts.
AB  - The effects of endodontic cements on the cell cycle of MG63 osteoblasts cultured
      in vitro have been examined. Three groups of compounds were tested. Group I
      encompassed zinc oxide- and eugenol-based cements (Tubliseal, Argoseal, N2),
      group II consisted of cements with a phenol group other than eugenol (AH26,
      Forfenan, Methode R/R), and group III included CaOH-based cements (Biocalex,
      Endocalex). The cell cycle of MG63 cells was analyzed by flow cytometry; the DNA
      content was evaluated by means of the propidium iodide uptake method, whereas the
      proportion of cells in the S phase was defined by the incorporation of
      bromodeoxyuridine later revealed by a specific antibody. The results showed that
      some root canal sealers could hamper the periapex healing processes by inhibiting
      the cell proliferation through a selective action on different phases of the cell
      cycle.

PMID- 7621015
TI  - Impact of TMJ radiographs on clinician decision making.
AB  - OBJECTIVES: This study examined the influence of lateral and frontal
      temporomandibular joint tomograms on the initial diagnosis and treatment plan of
      patients having facial or preauricular pain or temporomandibular joint disorders.
      STUDY DESIGN: Five or six general dentists, all with experience in treating
      patients with disorders of the temporOmandibular joint, examined records of 105
      patients from a university-based orofacial pain clinic. The examiners proposed a
      diagnosis and treatment plan for each patient without the benefit of tomograms.
      They then repeated this procedure after study of the radiographs. The impact of
      the radiographs was measured as the change in pre- versus postradiographic
      diagnosis and treatment plan. RESULTS: The availability of temporomandibular
      joint tomograms changed or modified diagnosis in 65% of the judgments and
      influenced treatment recommendations in 40%. These changes were substantive for
      21% of the diagnoses and 22% of the treatment plans. The strongest correlation to
      changes in both diagnosis and treatment plan was with radiographic detection of
      osseous changes. New information about condyle position had less effect on
      clinical decisions. CONCLUSIONS: These findings indicate that temporomandibular
      joint tomograms play a valuable role in influencing clinician's diagnosis and
      treatment plan of patients with disorders of the temporomandibular joint.

PMID- 7621014
TI  - Efficacy of TMJ radiographs in terms of expected versus actual findings.
AB  - OBJECTIVES: The purpose of this study was to measure the amount of new
      information contributed by temporomandibular joint tomograms beyond that
      anticipated by the patient's clinical presentation. STUDY DESIGN: The results of
      a clinical examination and history, including a video of patient interview, and
      dental casts of 105 patients with a temporomandibular disorder were presented to
      a panel of general dentist evaluators with some experience in temporomandibular
      disorders. These evaluators then described the radiographic findings they
      anticipated. Lastly they examined temporomandibular joint tomograms for each of
      the study patients and scored their findings. RESULTS: The temporomandibular
      joint tomograms revealed unanticipated osseous changes in 61% of case judgments
      of condyles and 47% for the temporal bone or 34% and 22%, respectively, when
      subtle changes were excluded. Unexpected condyle positional findings were
      revealed in 31% of the patients. When stratified by clinical class,
      osteoarthritis and internal derangement, false-positive and false-negative
      interpretations were 12.1% and 25.5%, respectively, for osteoarthritis, and 12.2%
      and 17.3% for derangement. CONCLUSIONS: The fairly high rate of unexpected new
      osseous and positional findings supports the need for tomograms in patients with
      a clinical diagnosis of derangement or osteoarthritis.

PMID- 7621016
TI  - Radiographic signs of temporomandibular joint osteoarthrosis and internal
      derangement 30 years after nonsurgical treatment.
AB  - The aim of this study was to evaluate with radiographs the long-term status of
      temporomandibular joints that were treated nonsurgically for reducing disk
      displacement (group 1) or permanent disk displacement (group 2) 30 years ago.
      Transcranial and transpharyngeal radiographs were made before (T1), 2 to 4 years
      after (T2), and 30 years after (T3) nonsurgical treatment in 65 former patients
      with temporomandibular joint osteoarthrosis. To control the results for aging 35
      matched subjects (group 3) underwent the same radiographic examination. The
      number and severity of radiographically visible degenerative changes increased
      significantly from T1 through T2 to T3 in group 1 and in group 2. The increase in
      these changes was not simply caused by aging, because in approximately three
      quarters of the temporomandibular joints in group 3, no radiographically visible
      degenerative changes were found. At all occasions group 2 showed significantly
      more severe changes than group 1. At T3 in 64% of the temporomandibular joints in
      group 1, no or only slight radiographically visible degenerative changes were
      observed, whereas in 86% of the temporomandibular joints in group 2, moderate to
      severe changes were observed. A persisting reducing disk displacement in part of
      the temporomandibular joints in group 1 might explain this significant
      difference. In 79% of the temporomandibular joints with moderate to severe
      radiographically visible degenerative changes at T1, no or only slight
      progression in the extent of these changes was seen between T2 and T3. Apparently
      a radiographically stable end stage may be reached within a few years after
      permanent displacement in most cases. It was concluded that in temporomandibular
      joints with reducing disk displacement, no or only slight radiographically
      visible degenerative changes develop, even if this condition persists for several
      decades. On the other hand, in temporomandibular joints with permanent disk
      displacement, radiographically visible degenerative changes are extensive in the
      vast majority of cases.

PMID- 7621017
TI  - Teaching radiographic localization in dental schools in the United States and
      Canada.
AB  - Although radiographic localization is an essential element of the practices of
      radiography and radiology, its incorporation into the dental curriculum has not
      previously been studied. This project surveyed dental schools in the United
      States and Canada on the relative amount of time that was given to instruction in
      various localization techniques and instructor opinion of the adequacy of
      training in localization skills. Ninety-eight percent of all dental schools
      returned questionnaires. Respondents who felt that teaching time was inadequate
      had mean rank time scores that were 40% less for total localization instruction
      and 57% less for teaching anatomic clues of the Buccal Object Rule than those who
      felt that teaching time was adequate. Because the Buccal Object Rule, cues, and
      cues represent the definitive dose-reducing approach to radiographic localization
      and because the Buccal Object Rule is readily applied across a broad range of
      clinical disciplines and activities, we recommend that this concept be
      incorporated into the curricula of all dental schools.

PMID- 7621018
TI  - Trigeminal neuralgia and multiple sclerosis. A complex diagnosis.
AB  - Trigeminal neuralgia is a well-recognized complication in patients with multiple
      sclerosis. A case report is presented that describes multiple sclerosis in a
      middle-aged man with otherwise classical unilateral trigeminal neuralgia who
      demonstrated a variable response to pharmacologic and surgical intervention. The
      case highlights the difficulties of diagnosis when trigeminal neuralgia occurs
      concurrently with multiple sclerosis.

PMID- 7621019
TI  - Complete duplication of the mandibular canal: case report.

PMID- 7621020
TI  - Photography for arthroscopy documentation.

PMID- 7621021
TI  - Disk position before and after modified condylotomy in 80 symptomatic
      temporomandibular joints.
AB  - OBJECTIVE: Our primary objective was to determine the frequency of disk reduction
      after modified condylotomy and whether the type of displacement affected outcome.
      DESIGN: We classified reducing disk displacements from magnetic resonance images
      of 80 symptomatic temporomandibular joints before modified condylotomy. Disk
      position was reassessed after surgery. RESULTS: The disk and condyle typically
      move in reciprocal directions. The disk was reduced by surgery in 79% of the
      joints. The rate of reduction varied by the type of displacement, but the
      differences between the groups were not statistically significant. CONCLUSION:
      This finding reaffirms that modified condylotomy has a high rate of disk
      reduction. The unexpected observation that the increase in joint space resulting
      from the surgery typically permitted a variable degree of spontaneous movement of
      the disk has implications for the nature of osteoarthrosis and internal
      derangement and for surgical treatments intended to reduce the risk.

PMID- 7621022
TI  - Relationship between fractures of the mandibular angle and the presence and state
      of eruption of the lower third molar.
AB  - OBJECTIVES: This study attempted to relate the incidence of fractures at the
      mandibular angle with the presence and state of eruption of lower third molars.
      STUDY DESIGN: The records and radiographs of 200 patients with mandibular
      fractures were examined. The presence and degree of impaction of lower third
      molars were assessed for each patient and related to the occurrence of fractures
      of the mandibular angle. Data were analyzed by chi-square statistic and the
      Student's t test. RESULTS: The incidence of angle fractures was found to be
      significantly greater when unerupted lower third molars were present (p < 0.001).
      Bilateral unerupted third molar teeth predisposed to a fracture at the angle
      significantly more than unilateral unerupted third molars (p < 0.01).
      Furthermore, the amount of bony space occupied by an unerupted third molar tooth
      directly related to the weakness of that area of bone (p < 0.001). CONCLUSIONS:
      This study provides clinical evidence to suggest that unerupted third molar teeth
      weaken the mandibular angle both quantitatively and qualitatively.

PMID- 7621023
TI  - Incision properties and thermal effects of three CO2 lasers in soft tissue.
AB  - OBJECTIVES: It was the aim of this study to determine thermal and histologic
      events resulting from soft tissue incision with three CO2 lasers: one emitting
      light energy via a hollow waveguide at 9.3 microns; the others emitting light
      energy at 10.6 microns, one via a hollow waveguide, the other through an
      articulated arm delivery system. STUDY DESIGN: Thirty standardized incisions were
      made in the oral mucosa of pig's mandibles with three different lasers at actual
      power levels of 1, 4 and 12 W. Thermal events were recorded with thermocouples,
      and a histologic examination was performed to determine vertical and horizontal
      tissue damage as well as incision depth and width. RESULTS: Thermal and
      histologic results were related to parameters and beam characteristics rather
      than wavelength. CONCLUSION: In addition to wavelength, many variables can
      contribute to the surgical characteristics of a laser.

PMID- 7621024
TI  - Clinical and in vitro evaluation of mandibular angle fracture fixation with the
      two-miniplate system.
AB  - More stable fixation and greater resistance against infection are achieved in
      mandibular angle fractures if the two-miniplate-fixation technique is used. One
      plate is applied at the superior border and a second plate is applied at the
      inferior border of the buccal cortex. Strong support for this argument was
      demonstrated in these in vitro and pilot clinical studies. It is concluded that
      the two-miniplate-fixation technique is indicated in cases of mandibular angle
      fracture to achieve stability of the fracture site and early mobility of the jaw.

PMID- 7621025
TI  - Prevalence of oral lichen planus in patients with diabetes mellitus.
AB  - The purpose of this study was to determine the prevalence of oral lichen planus
      in a population of patients with diabetes mellitus compared with a control
      population and to determine if patient medications had any influence on the
      presence of such lesions. Two hundred seventy-three patients with diabetes and an
      identical number of age-, gender- and race-matched controls were examined for
      clinical evidence of oral lichen planus. Patient medication histories were also
      obtained from each group. Eleven diabetic patients (4%) and eight control
      patients (3%) had clinical evidence of oral lichen planus. Ingestion of
      nonsteroidal anti-inflammatory drugs or angiotensin-converting enzyme inhibitors
      was associated with the presence of oral lichen planus lesions in six patients.
      There was no apparent association of diabetes and oral lichen planus in this
      population, and the ingestion of medications known to cause lichenoid mucosal
      reactions had no influence per se on the presence of oral lichen planus lesions
      (p > 0.05). However, the type of medication ingested by those patients who had
      oral lichen planus lesions was either nonsteroidal anti-inflammatory drug or
      angiotensin-converting enzyme inhibitor, which was a significant association (p <
      0.00).

PMID- 7621026
TI  - Quantitative determination of immunologic components of salivary gland secretion
      in long-term, event-free pediatric oncology patients.
AB  - OBJECTIVES: Chemotherapy influences the human immune system. Salivary alterations
      occur during cancer treatment. In this article we examine the salivary
      immunoglobulin content in pediatric patients who were long-term event-free and
      correlate these findings with different oral factors. STUDY DESIGN: Fifty-two
      children of a study group and 63 children of a control group were examined at our
      University Hospital. Caries prevalence and plaque index were scored. Whole saliva
      samples were taken for determination of slgA and IgG concentrations and
      Streptococcus mutans and Lactobacillus counts. For statistical analysis the
      Dental Survey Plus (Providence Software Services, Bristol, England) software
      package was used. RESULTS: Concentrations of slgA and IgG were within normal
      limits in both groups; slgA level increased with age. A negative correlation
      between slgA concentration and caries experience was not found in all age groups.
      No correlation with other salivary parameters was found. CONCLUSION: Salivary
      content of slgA and IgG can return to normal after cytotoxic therapy in these
      children. Salivary IgA seem to play a role in the development of dental caries in
      this population.

PMID- 7621027
TI  - Helicobacter pylori in the oral cavity. A critical review of the literature.
AB  - Helicobacter pylori is now generally accepted as a key etiologic agent in peptic
      ulcer disease as well as in gastric cancer. Dental plaque has been implicated as
      a possible source of H. pylori by studies that used culture, biochemical, nucleic
      acid, and immunologic analyses. Variation in the sensitivities of detection by
      these different reported assays may reflect the methods used, technical
      difficulties, microbiota complexes, geographic distribution, and host response.
      The finding of H. pylori in dental plaque also suggested that dental workers may
      be at increased risk of acquiring H. pylori infection from occupational exposure.
      We review the available data concerning the presence of this important pathogen
      in the oral cavity and its potential to be acquired by dental workers. Knowledge
      of this organism's route of transmission may aid in the development of
      therapeutic procedures to stop its potential spread.

PMID- 7621028
TI  - Oral histoplasmosis in HIV-infected patients. A report of two cases.
AB  - Histoplasmosis is a fungal infection caused by the organism Histoplasma
      capsulatum. Disseminated disease usually occurs in immunosuppressed patients or
      in patients with chronic illnesses. Although relatively uncommon, histoplasmosis
      has been reported in patients with AIDS, and oral lesions have been noted on
      multiple sites and in various clinical presentations. We present two HIV-positive
      cases with oral lesions as the initial signs of histoplasmosis. Both patients
      responded well to IV amphotericin B but later suffered recurrences despite being
      maintained on systemic antifungal therapy.

PMID- 7621029
TI  - Nifedipine-induced gingival hyperplasia. A comprehensive review and analysis.
AB  - A comprehensive review of the literature and analysis of the clinical history,
      mechanisms, pathogenesis, histology, and management of nifedipine-induced
      gingival hyperplasia is reported. A correlation to age, gender, drug, dosage,
      duration of drug therapy, location, and mode of treatment is discussed. The case
      report presented provides a model for management of nifedipine-induced gingival
      hyperplasia and other drug-induced gingival hyperplasia.

PMID- 7621030
TI  - Immunoglobulin gene rearrangements in lymphoplasmacytic infiltrates of labial
      salivary glands in Sjogren's syndrome. A possible predictor of lymphoma
      development.
AB  - OBJECTIVES: Sjogren's syndrome is an autoimmune disorder in which patients have a
      well-recognized risk of developing malignant lymphoma. Although some clinical
      parameters may herald the onset of lymphoma, few reliable histologic or molecular
      markers are available that predict progression to a malignant lymphoproliferative
      disorder. The purpose of this study was to identify the prevalence of
      immunoglobulin heavy chain monoclonality in labial gland biopsies of patients
      with Sjogren's syndrome and to compare this to clinical outcome. STUDY DESIGN:
      The polymerase chain reaction was applied to 76 sequential labial salivary gland
      biopsies from patients under investigation for Sjogren's syndrome. A seminested
      polymerase chain reaction technique was used on DNA extracted from formalin
      fixed, paraffin-embedded tissue to amplify the V-D-J region of the immunoglobulin
      heavy chain gene. Thirty-four randomly selected labial salivary glands that
      showed nonspecific sialadenitis from patients without Sjogren's syndrome were
      used as controls. RESULTS: Monoclonality, as defined by a single band on
      polyacrylamide gel electrophoresis was detected in 11 cases (14.5%). Of cases
      that showed monoclonality, four patients were subsequently diagnosed with
      extrasalivary lymphoma. In each case the rearranged bands in the lip biopsy and
      the lymphoma were the same size. In one patient who later developed lymphoma, a
      monoclonal rearranged immunoglobulin band was not identified. In addition, no
      cases of the translocation t(14;18) were identified by polymerase chain reaction
      in any of the lip biopsies showing heavy chain monoclonality or in any of the
      extrasalivary gland lymphomas. CONCLUSIONS: These results suggest that monoclonal
      immunoglobulin heavy chain gene rearrangements are a relatively common finding in
      patients with Sjogren's syndrome and may prove to be a useful marker for
      predicting the progression to, and early detection of malignant lymphoma.

PMID- 7621031
TI  - T-cell receptor V alpha and V beta gene use by infiltrating T cells in labial
      glands of patients with Sjogren's syndrome.
AB  - Sjogren's syndrome is an autoimmune disease affecting the exocrine glands; it is
      thought to result from T-cell-mediated damage. In the labial glands of 20
      patients with Sjogren's syndrome, infiltrating T cells were immunohistochemically
      characterized, and T-cell receptor (TCR) gene expression was examined with a
      method based on polymerase chain reaction. Most of these lymphocytes expressed
      CD3, CD4, CD45RO, and TCR alpha beta, whereas less than 5% of them expressed CD25
      and CD69. The TCR V alpha and V beta genes expressed in peripheral blood
      mononuclear cells were diverse, whereas the TCR V alpha and V beta repertoires in
      the labial glands were more restricted but were still heterogeneous. The
      predominantly used V alpha and V beta families in the labial glands, when
      compared with those in peripheral blood mononuclear cells, were found to vary in
      individual patients and also to differ from patient to patient. Thus the T-cell
      population in the labial glands was polyclonal but showed a more restricted
      pattern than that seen in peripheral blood mononuclear cells.

PMID- 7621032
TI  - Carcinosarcoma of salivary glands with unusual stromal components. Report of two
      cases and review of the literature.
AB  - Carcinosarcomas are rare neoplasms that exhibit heterologous malignant epithelial
      and stromal components. We report two cases of salivary gland carcinosarcoma with
      immunohistochemical analysis and clinical follow-up that provide insights into
      the pathogenesis and behavior of these tumors. In one case, a 51-year-old black
      woman had a 15-year history of a hard, asymptomatic, infraauricular mass that
      recently had undergone rapid growth. The tumor showed adenocarcinoma and
      osteosarcoma. She died 9 months after diagnosis. In another case, a 78-year-old
      white woman had a large soft palate mass that had been present for several years
      and had recently caused dysphagia. The tumor showed adenocarcinoma and
      leiomyosarcoma. The patient is alive at 9 months follow-up. Although malignant
      epithelial and stromal components characterize carcinosarcomas,
      immunohistochemical studies suggest that both elements are derived from a common
      precursor cell, possibly of myoepithelial origin. These cases support this
      concept and perhaps suggest a spectrum of differentiation that this precursor
      cell may exhibit.

PMID- 7621033
TI  - Pleomorphic adenoma of the salivary glands. Clinicopathologic study of 206 cases
      in Zimbabwe.
AB  - A review of 206 pleomorphic adenomas seen over a 10-year period was carried out.
      Fifty-eight percent of the tumors were in females. The tumor was common in the
      3rd, 4th, and 5th decades with 39.8% of the tumors occurring in the parotid
      gland.

PMID- 7621034
TI  - Evaluation of serum beta 2-microglobulin in premalignant and malignant lesions of
      the oral cavity.
AB  - Serum beta-2-microglobulin was estimated in patients with oral leukoplakia, oral
      submucous fibrosis, and oral cancer. The results were compared with that of an
      equal number of age- and sex-matched healthy controls. A definite increase in the
      level of beta 2-microglobulin was observed in patients with oral submucous
      fibrosis and oral cancer. Though the level of beta 2-microglobulin was found to
      be high in oral leukoplakia, it was not statistically significant. Further
      studies will validate the role of beta 2-microglobulin estimation to predict the
      malignant potential of oral submucous fibrosis.

PMID- 7621035
TI  - An assessment of oral cancer underregistration at the Connecticut Tumor Registry.
AB  - The purpose of this study was to investigate whether and to what extent cases of
      oral cancer diagnosed through the University of Connecticut Health Center Oral
      Pathology Biopsy Service went unregistered by the Connecticut Tumor Registry
      during the period 1984 to 1988. All Oral Pathology Biopsy Service pathology
      reports generated from 1984 to 1988 were reviewed to identify diagnosed oral
      cancer cases (International Classification of Diseases, 9th revision codes 140,
      141, 143 to 145). The names of all identified patients were computer-linked to
      previously registered cases. Nineteen (8.6%) of the 221 reportable cases of oral
      cancer diagnosed through the Oral Pathology Biopsy Service from 1984 to 1988 went
      unregistered. The 19 unregistered cases represented 1.6% of all known Connecticut
      oral cancer cases diagnosed during the period. The finding of a past, albeit
      small, "gap" in oral cancer cases registered with the Connecticut Tumor Registry
      suggests that oral pathologists should confirm that cases of oral cancer
      diagnosed through their pathology services are being registered by their regional
      tumor registries.

PMID- 7621036
TI  - Use of mineral trioxide aggregate for repair of furcal perforations.
AB  - The histologic response to intentional perforation in the furcations of 28
      mandibular premolars in seven dogs was investigated. In half the teeth, the
      perforations were repaired immediately with either amalgam or mineral trioxide
      aggregate; in the rest the perforations were left open to salivary contamination
      before repair. All repaired perforations were left for 4 months before histologic
      examination of vertical sections through the site. In the immediately repaired
      group, all the amalgam specimens were associated with inflammation, whereas only
      one of six with mineral trioxide aggregate was; further, the five noninflamed
      mineral trioxide aggregate specimens had some cementum over the repair material.
      In the delayed group, all the amalgam specimens were associated with
      inflammation; in contrast only four of seven filled with the aggregate were
      inflamed. On the basis of these results, it appears that mineral trioxide
      aggregate is a far more suitable material than amalgam for perforation repair,
      particularly when used immediately after perforation.

PMID- 7621038
TI  - Apical foraminal openings in human teeth. Number and location.
AB  - One hundred forty extracted permanent human teeth were prepared for examination
      with a scanning electron microscope to determine the number of foramina, their
      distances from the apices, and their locations. In most of the specimens, the
      root canals deviated to one side and ended short of the apices. Some specimens
      showed interradicular openings; others had configurations on the top of the
      apices that were similar to the crest on a helmet.

PMID- 7621037
TI  - Gaining access to calcified canals.
AB  - Gaining entrance to calcified canals can be very difficult and at times
      impossible. With the aid of the EDTA-Urea preparation (RC-Prep, Premier Dental
      Products, Norristown, Pa.) and the surgical length contra-angle burs, the task
      can be facilitated. The use of the multipurpose probe reduces the problem of
      perforation. We may now be able to gain access and treat a greater number of
      calcified canals.

PMID- 7621039
TI  - Electronic thermography for the assessment of mild and moderate temporomandibular
      joint dysfunction.
AB  - Today facial heat emission patterns may be rapidly obtained and quantified with
      the use of advanced electronic thermography units that have the promise of being
      a nonionizing, noninvasive, low-cost diagnostic alternative for the evaluation of
      temporomandibular joint disorders. This study design measured the use of
      electronic thermography as a tool to select between asymptomatic (control)
      subjects and a patient group with mild to moderate temporomandibular joint
      disorders. Study populations consisted of 24 asymptomatic (control) subjects and
      20 patients with (1) either locked or unlocked temporomandibular joints, (2)
      varying degrees of limitation of mouth opening, (3) mild to moderate muscle pain,
      and (4) mild to moderate temporomandibular joint arthralgia. The results
      indicated that the control group demonstrated a high level of thermal symmetry
      over the temporomandibular joint region. The patient group demonstrated a low
      level of thermal symmetry with a delta T value of 0.4 degrees C. The control
      group was selected from the patient group with 85% sensitivity (17 of 20), and
      92% specificity (22 of 24), and 89% overall accuracy (39 of 44), when selecting
      among the 44 subjects used in this study. The conclusion therefore is that
      electronic thermography shows promise as a method of diagnosing mild to moderate
      temporomandibular joint disorders.

PMID- 7621040
TI  - 3-D reconstruction of Ir-192 implant dosimetry for irradiating gingival carcinoma
      on the mandibular alveolar ridge.
AB  - A recurrent cancer in the gingiva has been treated by specially fabricating a
      dental acrylic appliance. This replica of the floor of the mouth, gums, and teeth
      was constructed with the use of a vinyl polysiloxine impression material. The
      tumor boundaries were marked in the fabricated appliance with four metal wires to
      localize the surface and periphery of the tumor. The appliance was molded to hold
      Ir-192 wires in near contact with the target surface and to allow afterloading. A
      specially designed lead shield was imbedded onto the dorsal surface of the
      appliance so as to reduce dose to the tongue and maxillary structures of the
      mouth. Simulation films and 3-D treatment planning were used to generate isodose
      distributions and to allow preplanning. The dose calculation algorithm was
      modified to account for the attenuation in the lead shield represented in three
      dimensions. The Ir-192 mold was successfully applied for 38 hours in two sessions
      1 week apart.

PMID- 7621041
TI  - To be or not to be: once again trauma centers are struggling to survive.

PMID- 7621044
TI  - The work of breathing.

PMID- 7621043
TI  - The challenge of trauma clinical trials: facilitation through understanding.
AB  - Coordinating trauma clinical trials is a relatively new role for trauma nurses.
      The authors examine the specific roles and responsibilities of the clinical
      research nurse coordinator (CRNC) within the surgical intensive care unit.
      Historical evolution of this challenging role is reviewed, and specific
      responsibilities of the CRNC are discussed. Additionally, ethical considerations
      and conclusions are presented.

PMID- 7621042
TI  - Evaluating diaphragm activity in trauma patients.
AB  - The diaphragm is the major respiratory muscle responsible for most of the
      inspiratory work of breathing. Bedside clinicians often overlook the need to
      assess the diaphragm or have never focused their attention on understanding the
      mechanisms behind this muscle. This article updates the trauma nurse on the
      anatomy and physiology of the diaphragm, reviews current methods for assessing
      diaphragm activity, and discusses research and diagnostic methods concerning the
      diaphragm. With heightened awareness of diaphragmatic function, clinicians may be
      able to improve the respiratory status of the trauma patient by preventing
      diaphragm fatigue or exhaustion.

PMID- 7621045
TI  - The trauma coordinator top 10: what I wish I had known.

PMID- 7621046
TI  - Can we care too much? Therapeutic nurse patient relationships.

PMID- 7621047
TI  - The future for nursing. Crossing boundaries through collaboration.

PMID- 7621048
TI  - Boundaries.

PMID- 7621049
TI  - June Werner, RN, MN, MSN, CNAA. CNM's "mentor of the year" winner. Interview by
      Linda Stake and Lisa Legge.

PMID- 7621050
TI  - Impact of healthcare reform. Interview by Marie Manthey.

PMID- 7621051
TI  - The unique preparation of nurses.

PMID- 7621052
TI  - Dyspnea and the larynx.
AB  - The larynx is an extremely important and complex part of our airway, and patients
      commonly seen by an allergist may have a large number of laryngeal problems that
      may be either totally or partially responsible for their presenting complaints.
      These problems may be structural in nature or may be related to abnormal motion
      of the vocal cords. A thorough knowledge of laryngeal anatomy, physiology, and
      possible pathology, combined with visualization of the larynx is necessary for
      accurate diagnosis.

PMID- 7621053
TI  - A 16-year-old girl with cough and abdominal pain.

PMID- 7621054
TI  - Latex allergy--an emerging healthcare problem. Latex Hypersensitivity Committee.

PMID- 7621055
TI  - Bela Schick Lecture. The allergist in the 21st century.

PMID- 7621056
TI  - Direct laryngoscopy with provocation: a useful method to distinguish acute
      laryngeal edema from nonorganic disease.
AB  - BACKGROUND: Acute laryngeal edema is a manifestation of anaphylaxis, is
      frequently sudden in onset and requires immediate treatment to prevent further
      airway compromise. Nonorganic disease such as globus hystericus may present with
      symptoms similar to acute laryngeal edema. Distinguishing life-threatening acute
      laryngeal edema from non-life-threatening disease may be difficult. OBJECTIVE: We
      present a patient in which direct laryngoscopy was used to distinguish acute
      laryngeal edema from nonorganic disease. METHODS: A case report of a woman who
      had presented to numerous emergency rooms with symptoms of cough, sensation of
      throat closing, and hoarseness when exposed to odors such as nail polish remover
      and musk cologne. She was treated repeatedly with subcutaneous epinephrine, oral
      diphenhydramine and intravenous methylprednisolone. Her history was not classic
      for IgE-mediated anaphylaxis and we challenged her with nail polish remover while
      visualizing her vocal cords with direct laryngoscopy. RESULTS: Upon challenge
      with an offending agent, her symptoms were again suggestive of life-threatening
      laryngeal edema. Direct laryngoscopy, however, revealed no objective evidence of
      airway obstruction. CONCLUSION: Direct laryngoscopy with provocation is useful in
      distinguishing acute laryngeal edema from nonorganic disease.

PMID- 7621057
TI  - Deliberate hymenoptera sting challenge as a diagnostic tool in highly selected
      venom-allergic patients.
AB  - BACKGROUND: Open environment and working conditions close to abundant insects of
      the order Hymenoptera should be avoided as much as possible by patients allergic
      to Hymenoptera venom who do not receive venom immunotherapy. After having
      experienced accidental field re-stings not resulting in a systemic reaction, some
      of these patients may be willing to resume normal life and working habits. Since
      venom-specific IgE usually remains elevated in these patients, repeated skin
      tests or RASTs are not helpful in identifying disappearance of their venom
      allergy. OBJECTIVE: The purpose of this study was to evaluate the usefulness of
      deliberate live sting challenge as a diagnostic tool in highly selected venom
      allergic patients who had initially refused venom immunotherapy. METHODS: Two
      cases are reported of bee venom-allergic patients who had previously refused
      venom immunotherapy and subsequently experienced honeybee field re-stings not
      resulting in systemic reactions. Two to three years later, their skin tests
      remained positive for bee venom. A third patient allergic to Vespa orientalis who
      had negative skin tests to all available venoms was denied venom immunotherapy
      due to lack of proper commercial venom. Because none of the patients was
      receiving venom immunotherapy the military service personnel concluded they still
      had venom allergy and rejected them from the highly prestigious service. All
      three patients were anxious to confirm the disappearance of their venom allergy
      and we used deliberate live sting challenges for that purpose. RESULTS: Two to
      three years after their initial systemic reactions live sting challenges were
      well tolerated by the three patients. They felt free to resume their normal life
      habits and were allowed to begin military service without further limitations.
      CONCLUSION: Deliberate insect stings using appropriate safety precautions should
      be considered a diagnostic tool in selected allergic patients who do not receive
      venom immunotherapy but in whom a reliable history of negative field re-stings
      can be obtained despite positive skin tests and in those who continue to have
      inconclusive venom skin tests.

PMID- 7621058
TI  - Evaluation of the inhibitory effects of budesonide on the mitogen-induced or the
      allergen-induced activation of blood mononuclear cells isolated from asthmatic
      patients.
AB  - BACKGROUND: Corticosteroids are thought to be effective in the treatment of
      allergic reactions including bronchial asthma because they not only have anti
      inflammatory effects, but also downregulate the processes of T-cell activation.
      OBJECTIVE: To evaluate in vitro the inhibitory activity of budesonide, a widely
      used inhaled corticosteroid, on allergen-induced mononuclear cell activation.
      METHODS: Thirty-one atopic asthmatic patients, sensitized to Dermatophagoides
      pteronyssinus (Der p) were studied. Peripheral blood mononuclear cells isolated
      from these patients were used to determine the ability of budesonide to inhibit
      (1) the proliferative response of blood T-lymphocytes to Der p allergen extract
      and to phytohemoagglutinin (PHA) and (2) the release of different cytokines known
      to modulate the interaction between T-lymphocytes and monocytes in the allergic
      processes. RESULTS: A significant T-cell proliferation was observed both in the
      presence of PHA (P < .001) and that of Der p allergen extract (P < .05), and was
      associated with increased release of interleukin-2 [IL-2 (respectively P < .001
      and P < .01)], gamma-interferon [gamma-IFN (respectively P < .001 and P < .01)],
      granulocyte-macrophage colony-stimulating factor [GM-CSF (respectively P < .01
      and P < .001)], interleukin-1 beta [IL-1 beta (respectively P < .05 and P <
      .01)], and tumor necrosis factor-alpha [TNF-alpha (P < .05 each comparison)]. The
      addition at the beginning of the cell cultures of different concentrations (from
      10(-10) M to 10(-7) M) of budesonide, and as control of dexamethasone, induced a
      dose-dependent inhibition of T-cell proliferation, in response to PHA and Der p.
      Budesonide at the lowest concentrations tested (10(-10) M and 10(-9) M) was more
      effective than dexamethasone. Budesonide was also more active than dexamethasone
      in inhibiting the release of IL-2, gamma-IFN, IL-1 beta and GM-CSF (in both PHA
      stimulated and Der p-stimulated blood mononuclear cell cultures) and TNF-alpha
      (in Der p-stimulated blood mononuclear cell cultures). CONCLUSIONS: Budesonide is
      equally or more effective than dexamethasone in inhibiting the allergen-induced T
      cell proliferation and in reducing the release of cytokines by allergen
      stimulated blood mononuclear cells.

PMID- 7621059
TI  - Continuous versus frequent intermittent nebulization of albuterol in acute
      asthma: a randomized, prospective study.
AB  - BACKGROUND: In acute severe asthma the optimal dose, frequency, duration and
      method of administration of beta-2 agonists is unknown. No study to date has
      evaluated the efficacy of high dose beta-2 agonists beyond the initial two hours.
      OBJECTIVE: (1) To determine whether high-dose continuous nebulization of
      albuterol (7.5 mg/h) is as safe and as efficacious as high-dose intermittent
      nebulization of albuterol (2.5 mg every 20 minutes) for four hours. (2) To
      evaluate whether there is a continual improvement using high dose therapy beyond
      two hours. METHODS: We devised a simple means of continuous nebulization
      calibrated to deliver 7.5 mg albuterol per hour. Twenty-two nonsmoking, patients
      with acute, severe asthma who presented to the emergency department with less
      than 60% predicted normal PEFR were randomized to either the continuous or
      intermittent group. All patients received intravenously 125 mg methyl
      prednisolone on initiation of the study. No theophylline was administered.
      Spirometry and vital signs were measured at baseline and every 30 minutes
      thereafter. Electrocardiograms were obtained on all patients and all patients had
      continuous cardiac monitoring. RESULTS: Both groups doubled their baseline
      spirometric values over the four-hour period (P < .0001). The FEV1 did not differ
      significantly between regimens at any time interval. Improvement from 120 minutes
      to 240 minutes was statistically significant (P < .0001). There was no
      significant difference in vital signs at the end of the study compared with
      baseline in either group, nor between the two groups at any time interval.
      CONCLUSION: High-dose continuous nebulization of albuterol is as safe and as
      efficacious as intermittent nebulization of albuterol in the early treatment of
      asthma in an emergency department. To our knowledge, this is the first study
      showing continued significant improvement beyond the initial two hours of therapy
      using high dose nebulized beta-2 agonists.

PMID- 7621060
TI  - Immunoblot study of IgE binding allergens in celery roots.
AB  - OBJECTIVES: The purpose of this study was to characterize the IgE binding
      components of celery root by immunoblot analysis and to investigate the cross
      reactive nature of the allergens. BACKGROUND: Sensitization to celery is very
      common in patients hypersensitive to mugwort pollen and birch pollen, and is due
      to cross-reactions of allergen-specific IgE antibodies. Recently, the pan
      allergen profilin has been identified as an important cross-reactive allergen in
      celery, birch pollen and mugwort pollen. Very few data, however, on additional
      celery allergens are available. METHODS: Sera of 38 patients with an isolated or
      combined sensitization to birch pollen, mugwort pollen, and celery were
      investigated by immunoblot and immunoblot inhibition techniques using celery
      extract and purified Bet v I, the major allergen from birch pollen. The selection
      of sera was based on serologic sensitization, independent of clinical
      manifestations. Celery profilin was affinity isolated and analyzed by
      immunoblotting with patients' sera as well as with rabbit polyclonal antiserum
      raised against celery profilin. RESULTS: Only weak IgE binding occurred on celery
      immunoblots in the patient groups with a negative RAST to celery. Sera of 6/8
      patients with a birch pollen/celery sensitization recognized a 16-kDa celery
      allergen that cross-reacted with Bet v I in immunoblot inhibition experiments. In
      the mugwort pollen/celery and birch pollen/mugwort pollen/celery patient groups,
      the sera of 6/16 patients contained IgE that bound to a 15 to 16-kDa double band
      identified as celery profilin. Furthermore, three sera of the birch
      pollen/mugwort pollen/celery group appeared to contain IgE antibodies against
      carbohydrate determinants. CONCLUSIONS: The 16-kDa Bet v I-related celery protein
      appears to be an important allergen for patients sensitized to birch pollen and
      celery. In contrast IgE binding to celery profilin appears to be more important
      in patients with an additional sensitization to mugwort pollen.

PMID- 7621061
TI  - Epidermal Langerhans' cells and their function in the skin immune system.
AB  - OBJECTIVE: This article reviews the role of the epidermal Langerhans' cell in
      contact dermatitis and atopic dermatitis. Included in this review are sections on
      the historical, morphologic, immunohistochemical, and electron microscopic
      aspects of the Langerhans' cell. Differences between freshly isolated and
      cultured Langerhans' cells are reviewed in terms of cell surface markers and
      functional differences. The different IgE binding structures on the surface of
      Langerhans' cells are reviewed with discussion of their possible roles. The
      effects of different cytokines in the microenvironment are also commented upon.
      Other diseases where the Langerhans' cell is important such as histiocytosis X,
      HIV-1 infection, and skin graft rejection are briefly reviewed. DATA SOURCES:
      English literature search (1974-1994), indexing terms: Langerhans' cells, atopic
      dermatitis, IgE. STUDY SELECTION: The purpose of this paper is to review the most
      recent knowledge of Langerhans' cell function and relate this to the
      allergist/immunologist. RESULTS/CONCLUSIONS: Epidermal Langerhans' cells play a
      central role in the immune response in exhibiting multiple cell-surface receptors
      and secreting a variety of cytokines that are important in the pathogenesis of
      contact dermatitis, atopic dermatitis, histiocytosis X, HIV-1 infection, and skin
      graft rejection.

PMID- 7621062
TI  - Immediate hypersensitive reactions to buckwheat ingestion and cross allergenicity
      between buckwheat and rice antigens in subjects with high levels of IgE
      antibodies to buckwheat.
AB  - BACKGROUND: Immediate hypersensitive reactions induced by buckwheat ingestion are
      considered to be IgE-mediated. Some subjects, however, develop no immediate
      adverse reactions after buckwheat ingestion despite high levels of buckwheat
      specific antigens IgE. The mechanism is unknown. OBJECTIVE: To investigate the
      mechanisms. METHODS: RAST for buckwheat and rice and RAST inhibition between
      these antigens were performed using sera from 23 buckwheat-sensitive subjects and
      30 buckwheat-tolerant subjects who had IgE antibodies for both buckwheat and
      rice. RESULTS: RAST values for buckwheat and rice were significantly correlated
      with each other (P < .01) in the buckwheat-tolerant group, but not in the
      buckwheat-sensitive group. This suggests the IgE antibodies from the subjects
      without any overt symptoms after buckwheat ingestion recognize the cross-reactive
      epitope between buckwheat and rice, whereas the IgE antibodies from those with
      immediate reactions to buckwheat ingestion do not. RAST inhibition assays were
      performed to evaluate this. RAST inhibition of heterogeneous combination of
      inhibitor and disc antigen such as rice and buckwheat was significantly smaller
      than that of homologous combination of rice and rice or buckwheat and buckwheat
      in the group with immediate symptoms after buckwheat ingestion. There was no
      significant difference in RAST inhibition between homologous and heterogeneous
      combinations in the group without the symptoms. CONCLUSIONS: There was cross
      reactivity with IgE antibodies between buckwheat and rice and IgE antibodies from
      the buckwheat-tolerant subjects with high levels of IgE antibodies from the
      buckwheat might recognize the epitopes on buckwheat antigens which cross-react
      with rice antigens, whereas IgE antibodies from the buckwheat-sensitive subjects
      might bind to buckwheat-specific epitopes.

PMID- 7621063
TI  - Very low frequency of latex and fruit allergy in patients with spina bifida from
      Venezuela: influence of socioeconomic factors.
AB  - BACKGROUND: The prevalence of latex allergy appears to be substantially higher in
      certain high risk groups, particularly in children with spina bifida. The source
      of this increase is presently unknown and may be due either to increased
      infantile exposure or to an intrinsic predilection for atopy in this condition.
      OBJECTIVE: We attempted to ascertain the prevalence of latex and tropical fruit
      allergy in children of lower socioeconomic strata with spina bifida from Caracas,
      Venezuela, who have limited operative and other medical exposure to latex.
      METHODS: Ninety-three unselected patients with spina bifida from clinic and
      hospital populations were prick tested with commercial (Stallergenes-Pasteur)
      latex extract and crude glove (Baxter-Triflex, 1/5 wt/vol) latex extract as well
      as with standardized mite and cockroach, 1/10 wt/vol, extracts (Hollister-Stier).
      An array of tropical fruits were also included in the battery of skin test
      materials, using the prick by prick method. Careful family and personal history
      for allergy as well as any reactions to rubber products were noted, placing
      emphasis on intraoperative anaphylaxis, number of operations and use of bladder
      catheters. RESULTS: Only four patients of the 93 skin tested (4.3%) were positive
      to latex. Atopy was not a predisposing factor for latex allergy and neither was
      the number of surgical interventions. No fruit allergy was found in this
      population and three of the four skin test-positive patients had facial
      angioedema when exposed to balloons. CONCLUSIONS: The very low incidence of latex
      allergy found in our patients with spina bifida could very well be due to a low
      level of rubber exposure as best exemplified in the use of nonlatex bladder
      catheters, frequently washed and resterilized surgeon's gloves, and low number of
      operations per patient. The fact that atopy was no more prevalent in children
      with spina bifida than in the general population in Venezuela strongly supports
      exposure level as the major factor determining latex sensitization.

PMID- 7621064
TI  - Cyclosporine A reduces T lymphocyte activity and improves airway
      hyperresponsiveness in corticosteroid-dependent chronic severe asthma.
AB  - BACKGROUND: Although cyclosporine A is proving effective for chronic severe
      asthma, its mechanism of action in this disease is unclear. OBJECTIVE: This open
      study was conducted to determine whether cyclosporine A therapy would reduce the
      degree of airway hyperresponsiveness and T lymphocyte activity. METHODS: After a
      6-week run-in period, nine patients with corticosteroid-dependent chronic severe
      asthma were treated with cyclosporine A (initial dose 5 mg/kg per day) for 12
      weeks. RESULTS: Weekly mean morning peak expiratory flow significantly increased
      in six subjects during the last 6 weeks of trial. Geographic mean PC20
      acetylcholine (the provocative concentration of acetylcholine required to cause a
      20% fall in FEV1) was 0.147 mg/mL before cyclosporine A treatment and increased
      to 0.216 mg/mL at 6 weeks and to 0.379 mg/mL at 12 weeks after treatment. The
      increase at 12 weeks was statistically significant (P < .05). The percentage of
      CD4-positive T lymphocytes bearing IL-2 receptor (a marker of T cell activation)
      in the peripheral blood decreased significantly at 6 weeks (P < .05), but
      returned to baseline value at 12 weeks, probably due to cyclosporine A dose
      reduction in seven subjects. Serum IgE levels and peripheral blood eosinophil
      counts, however, which are dependent on IL-4 and IL-5, respectively, were still
      significantly decreased at 12 weeks, suggesting lymphokine production remained
      suppressed even after cyclosporine A dose was reduced. CONCLUSION: Taken
      together, these data suggest that cyclosporine A may act in asthma, at least in
      part, by inhibition of T lymphocyte activation and by reducing the degree of
      airway hyperresponsiveness.

PMID- 7621065
TI  - Antigenic and allergenic relationships among airborne grass pollens in India.
AB  - BACKGROUND: Pollen from grasses (Poaceae) are predominant aeroallergens
      throughout the world including tropical countries. Studies from USA, Europe, and
      Australia have shown extensive allergenic/antigenic cross reactivity among the
      grass pollen allergens prevalent there. No such information is available about
      airborne grass pollens of tropical countries. OBJECTIVE: The present study was
      undertaken to explore common antigenic/allergenic components, if any, of five
      important grass pollens of India. METHODS: Intradermal tests (ID) were performed
      with pollen extracts of Cenchrus, Cynodon, Imperata, Pennisetum, and Sorghum in
      patients with nasobronchial allergy. ELISAs were performed for estimating the
      allergen-specific IgE in sera of patients eliciting markedly positive ID response
      (2+ to 4+). To detect cross reactivity, ELISA inhibition experiments were carried
      out using pooled patient sera and five grasses, individually, as inhibitors with
      different solid phase antigens. To evaluate common antigenic components in
      Cenchrus, Imperata, and Pennisetum pollen extracts, rocket immunoelectrophoresis
      (RIE) and ELISA inhibition were conducted using rabbit antisera. RESULTS: Among
      133 patients, Cynodon extract elicited markedly positive skin reactivity in most
      patients followed by Pennisetum, Imperata, Cenchrus, and Sorghum. A large number
      of patients showed markedly positive skin reactions and enhanced specific IgE
      levels to more than one grass pollen extract. ELISA inhibition experiments showed
      different degrees of cross reactivity among the grass pollens studied. Rocket
      immunoelectrophoresis and ELISA inhibition using rabbit antisera with homologous
      and heterologous pollen revealed the presence of shared antigenic components in
      Cenchrus, Imperata, and Pennisetum extracts. CONCLUSION: The varied dose-response
      curves obtained with ELISA inhibition using different inhibitors suggest the
      presence of both common and specific antigens/allergens in the grass pollens
      studied. Based on the extensive immunologic cross reactivity, among the tropical
      grass species, it may be possible to use mixed allergen preparations for allergy
      diagnosis and immunotherapy.

PMID- 7621066
TI  - Chromosomes, genes, and cancer.
AB  - For over 100 years, scientists have been investigating the role of genetic change
      in neoplasia. Dr. Felix Mitelman, a Professor in the Department of Clinical
      Genetics at the University Hospital in Lund, Sweden, describes the progression in
      thought and technology that has led to the identification and characterization of
      genetic changes leading to cancer at a chromosomal and molecular level.

PMID- 7621068
TI  - Oncogenes and tumor suppressor genes.
AB  - In the past 15 years, many of the mechanisms underlying the molecular origins of
      cancer have been uncovered, and a clear picture of the role of oncogenes and
      tumor suppressor genes in carcinogenesis has developed. This article reviews the
      mechanisms by which oncogenes and tumor suppressor genes participate in the
      creation of tumors.

PMID- 7621067
TI  - Cancer cytogenetics for clinicians.
AB  - Chromosomal changes have been detected in virtually all human tumor types, and
      many of these chromosomal abnormalities have been established as valuable
      diagnostic and prognostic factors. This article provides an overview of the
      chromosomal changes associated with human cancer and their clinical consequences.

PMID- 7621069
TI  - Stereotactic breast biopsy.
AB  - The substantial majority of questionable lesions detected by mammography are
      benign, and there is growing interest among health care professionals and
      patients in alternatives to surgical biopsy for diagnosing these lesions.
      Stereotactic breast biopsy is an x-ray guided method for localizing and sampling
      breast lesions discovered on mammography and considered to be suspicious for
      malignancy. Its use in sampling small, nonpalpable breast lesions has been
      investigated over the past 15 years, using fine-needle aspiration for cytology
      and, more recently, core-needle biopsy for histology. Multiple series comparing
      stereotactic biopsy with surgical biopsy have shown that stereotactic techniques
      accurately sample small lesions and have a sensitivity of 90 to 95 percent for
      breast cancer detection. State-of-the-art stereotactic breast biopsy is
      comparable in sensitivity to surgical biopsy, and the procedure is quicker,
      cheaper, and easier than the standard practice of preoperative, mammographically
      guided localization followed by surgical biopsy. In an age of miniaturization,
      stereotactic techniques provide miniature breast biopsies. The University of
      Chicago acquired the first prone stereotactic table in the United States in 1986,
      and we have found stereotactic breast biopsy to be a very good alternative for
      certain lesions that would otherwise require surgical biopsy for diagnosis. Most
      lesions (70 percent) sent to conventional biopsy at the University of Chicago
      between 1986 and 1989 were graded by observers as being in a low-suspicion
      category (less than 10 percent chance of malignancy based on mammographic
      findings), and the positive malignancy yield of this category of lesions was
      seven percent. These lesions were also examined with stereotactic fine-needle
      aspiration performed as a "piggy-back" procedure to the needle localization for
      surgery. The results of this study have led us to use stereotactic biopsy rather
      than surgical biopsy for low-suspicion lesions since then. We currently use
      stereotactic breast biopsy for about half the nonpalpable lesions considered for
      breast biopsy at our institution and find it to be reliable and readily accepted
      by informed patients. The introduction of automated core-biopsy guns has
      escalated interest in the technique, due to increased confidence in the
      histologic samples obtained and the ability to make specific benign diagnoses
      more frequently. Some centers have extended the potential use of stereotaxis to
      virtually all suspicious mammographic lesions, including those with a high
      probability of malignancy, to plan definitive surgery. Based on current
      estimates, there are now over 1,000 centers either investigating or using
      stereotactic biopsy for occult breast lesions.

PMID- 7621070
TI  - Cytokines and STATs: how can signals achieve specificity?

PMID- 7621071
TI  - Specific immunity to Listeria monocytogenes in the absence of IFN gamma.
AB  - Cytokine and cytokine receptor gene knockout mice provide powerful experimental
      systems to characterize the functions of these molecules in resistance to
      infectious disease. Such mice may also provide unique models of immune deficiency
      to learn whether manipulation of the immune response can overcome the specific
      dysfunction. We demonstrate that resistance of IFN gamma gene knockout (GKO-/-)
      mice to the intracellular bacterium Listeria monocytogenes is severely impaired
      compared with wild-type mice. However, immunization of GKO-/- mice with an
      attenuated L. monocytogenes strain generates antigen-specific CD8 T cell
      responses that can transfer immunity to naive hosts. Furthermore, vaccinated GKO
      /- mice themselves exhibit 20,000-fold increased resistance to challenge with
      virulent L. monocytogenes and this resistance appears to be CD8 T cell mediated.
      These studies demonstrate that vaccination-induced immunity can overcome the
      absence of a cytokine that is critical for resistance to acute infection.

PMID- 7621072
TI  - CD23 regulates monocyte activation through a novel interaction with the adhesion
      molecules CD11b-CD18 and CD11c-CD18.
AB  - CD23 is expressed on a variety of haemopoietic cells and displays pleiotropic
      activities in vitro. We report that in addition to CD21 and IgE, CD23 interacts
      specifically with the CD11b and CD11c, the alpha chains of the beta 2 integrin
      adhesion molecule complexes CD11b-CD18 and CD11c-CD18, on monocytes. Full-length
      recombinant CD23 incorporated into fluorescent liposomes was shown to bind to COS
      cells transfected with cDNA encoding either CD11b-CD18 or CD11c-CD18 but not with
      CD11a-CD18. The interaction was specifically inhibited by anti-CD11b or anti
      CD11c, respectively, and by anti-CD23 MAbs. The functional significance of this
      ligand pairing was demonstrated by triggering CD11b and CD11c on monocytes with
      either recombinant CD23 or anti-CD11b and anti-CD11c MAbs to cause a marked
      increase in nitrite-oxidative products and pro-inflammatory cytokines (IL-1 beta,
      IL-6, and TNF alpha). These CD23-mediated activities were decreased by Fab
      fragments of MAbs to CD11b, CD11c, and CD23. These results demonstrate that CD11b
      and CD11c are receptors for CD23 and that this novel ligand pairing regulates
      important activities of monocytes.

PMID- 7621073
TI  - HIV Tat represses transcription through Sp1-like elements in the basal promoter.
AB  - MHC class I genes are potently repressed by HIV Tat, which transactivates the HIV
      LTR. Tat represses class I transcription by binding to complexes associated with
      a novel promoter element, consisting of Sp1-like DNA binding sites. Transcription
      by other Sp1-dependent promoters, such as MDR1 and the minimal SV40 promoters, is
      also repressed by Tat, whereas the human beta-actin promoter is neither activated
      by Sp1 nor repressed by Tat. Tat repression can be overcome by a strong enhancer
      element. Thus, the SV40 72 bp enhancer element confers protection from Tat
      mediated repression on both the minimal SV40 promoter and the class I promoter.
      Surprisingly, Tat can activate the class I promoter in the presence of both the
      HIV TAR element and a strong upstream enhancer. These data demonstrate that Tat
      differentially affects Sp1-responsive promoters, depending on promoter
      architecture.

PMID- 7621074
TI  - Targeted disruption of the flk2/flt3 gene leads to deficiencies in primitive
      hematopoietic progenitors.
AB  - The flk2 receptor tyrosine kinase has been implicated in hematopoietic
      development. Mice deficient in flk2 were generated. Mutants developed into
      healthy adults with normal mature hematopoietic populations. However, they
      possessed specific deficiencies in primitive B lymphoid progenitors. Bone marrow
      transplantation experiments revealed a further deficiency in T cell and myeloid
      reconstitution by mutant stem cells. Mice deficient for both c-kit and flk2
      exhibited a more severe phenotype characterized by large overall decreases in
      hematopoietic cell numbers, further reductions in the relative frequencies of
      lymphoid progenitors, and a postnatal lethality. Taken together, the data suggest
      that flk2 plays a role both in multipotent stem cells and in lymphoid
      differentiation.

PMID- 7621075
TI  - Cytotoxic antibodies trigger inflammation through Fc receptors.
AB  - Pathogenic self-reactive antibodies are a significant cause of morbidity and
      mortality and contribute to both cytotoxic and immune complex-triggered
      inflammatory disorders, typified by rheumatic diseases, autoimmune hemolytic
      anemia, and thrombocytopenia. Roles have been proposed for Fc receptors,
      complement, and complement receptors in the pathogenesis of these disorders,
      although the contribution of each to autoimmune injury is unclear. gamma chain
      deficient mice lacking Fc gamma RI and Fc gamma RIII are resistant to the
      development of experimental immune hemolytic anemia induced by polyclonal rabbit
      anti-mouse red blood cell IgG antibodies. This resistance is primarily a
      consequence of ineffective erythrophagocytosis, resulting from the lack of Fc
      gamma Rs on mononuclear phagocytes. Similarly, gamma chain-deficient mice are
      completely resistant to the development of experimental immune thrombocytopenia
      induced by mouse anti-platelet antibodies. These data suggest that Fc receptors
      play an integral role in the pathogenesis of type II hypersensitivity and suggest
      potential therapeutic benefits of Fc receptor blockade.

PMID- 7621077
TI  - MHC-recognizing receptors: they're not just for T cells anymore.

PMID- 7621076
TI  - Severe colitis in mice with aberrant thymic selection.
AB  - Tg epsilon 26 mice display an arrest very early in T cell development that has a
      profound effect on the architecture of thymic stromal cells. We have recently
      demonstrated that transplantation of wild-type bone marrow cells restores the
      thymic microenvironment of fetal but not adult Tg epsilon 26 mice. Here, we
      report that T cell-reconstituted adult Tg epsilon 26 mice develop a spontaneous
      wasting syndrome characterized by extensive inflammation of the colon, resembling
      human ulcerative colitis. Colitis in these animals was marked by substantial
      infiltration of the colon by activated thymus-derived CD4+ T cells. Importantly,
      bone marrow-transplanted Tg epsilon 26 mice previously engrafted with a fetal Tg
      epsilon 26 thymus did not develop colitis. These results suggest that T cells
      selected in an aberrant thymic microenvironment contain a population of cells
      able to induce severe colitis that can be prevented by T cells that have
      undergone normal thymic development.

PMID- 7621078
TI  - Structural analysis of TCR-ligand interactions studied on H-2Kd-restricted cloned
      CTL specific for a photoreactive peptide derivative.
AB  - To study the interaction of the TCR with its ligand, the complex of a MHC
      molecule and an antigenic peptide, we modified a TCR contact residue of a H-2Kd
      restricted antigenic peptide with photoreactive 4-azidobenzoic acid. The
      photoreactive group was a critical component of the epitope recognized by CTL
      clones derived from mice immunized with such a peptide derivative. The majority
      of these clones expressed V beta 1-encoded beta chains that were paired with J
      alpha TA28-encoded alpha chains. For one of these TCR, the photoaffinity labeled
      sites were mapped on the alpha chain as a J alpha TA28-encoded tryptophan and on
      the beta chain as a residue of the C' strand of V beta 1. Molecular modeling of
      this TCR suggested the presence of a hydrophobic pocket that harbors this
      tryptophan as well as a tyrosine on the C' strand of V beta 1 between which the
      photoreactive side chain inserts. It is concluded that this avid binding
      principle may account for the preferential selection of V beta 1 and J alpha TA28
      encoded TCR.

PMID- 7621079
TI  - Strong agonist ligands for the T cell receptor do not mediate positive selection
      of functional CD8+ T cells.
AB  - Positive selection of functional CD8+ T cells expressing an MHC class I
      restricted T cell receptor can be induced in fetal thymus organ culture by class
      I-binding peptides related to the antigenic peptide ligand. Peptides that act as
      antagonist or weak agonist/antagonist ligands for mature T cells work efficiently
      in this regard. In the present study, we have investigated whether low
      concentrations of the original agonist peptide, or variants that still have a
      strong agonist activity can also mediate positive selection. The antigenic
      peptide did not induce positive selection at any concentration tested. A strong
      agonist variant was capable of stimulating the differentiation of TCRhi CD8+
      cells, giving the appearance of phenotypic positive selection. However, these
      cells lacked biological function, since they could not proliferate in response to
      antigen. The most efficient positive selection resulted with ligands that did not
      activate mature T cells or stimulate negative selection.

PMID- 7621080
TI  - CD28 costimulation can promote T cell survival by enhancing the expression of Bcl
      XL.
AB  - T cell activation through the TCR can result in either cell proliferation or cell
      death. The role of costimulatory receptors in regulating T cell survival has not
      been defined. Here, we present data demonstrating that CD28 costimulation
      enhances the in vitro survival of activated T cells. One mechanism for this
      enhancement is the ability of CD28 costimulation to augment the production of IL
      2, which acts as an extrinsic survival factor for T cells. In addition, CD28
      costimulation augments the intrinsic ability of T cells to resist apoptosis.
      Although CD28 signal transduction had no effect on Bcl-2 expression, CD28
      costimulation was found to augment the expression of Bcl-XL substantially.
      Transfection experiments demonstrated that this level of Bcl-XL could prevent T
      cell death in response to TCR cross-linking, Fas cross-linking, or IL-2
      withdrawal. These data suggest that an important role of CD28 costimulation is to
      augment T cell survival during antigen activation.

PMID- 7621081
TI  - Resistance to fever induction and impaired acute-phase response in interleukin-1
      beta-deficient mice.
AB  - We used gene targeting in embryonic stem cells to introduce an IL-1 beta null
      allele in mice. The IL-1 beta-deficient mice develop normally and are apparently
      healthy and fertile. The IL-1 beta null mice responded normally in models of
      contact and delayed-type hypersensitivity or following bacterial endotoxin LPS
      induced inflammation. The IL-1 beta-deficient mice showed equivalent resistance
      to Listeria monocytogenes compared with wild-type controls. In contrast, when
      challenged with turpentine, which causes localized inflammation and tissue
      injury, the IL-1 beta mutant mice exhibited an impaired acute-phase inflammatory
      response and were completely resistant to fever development and anorexia. These
      results highlight a central role for IL-1 beta as a pyrogen and a mediator of the
      acute-phase response in a subset of inflammatory disease models, and support the
      notion that blocking the action of a single key cytokine can alter the course of
      specific immune and inflammatory responses.

PMID- 7621082
TI  - A model study on rate of degradation of L-ascorbic acid during processing using
      home-produced juice concentrates.
AB  - The rate of degradation of L-ascorbic acid in solution has been investigated
      under varying conditions, such as temperature, level of dissolved oxygen, pH,
      amino acids, sugars and processing conditions. Changes in pH between pH 1.5 and
      7.0 accelerate L-ascorbic acid degradation. The most important factor that
      determines its stability is storage temperature, on which the rate of degradation
      of L-ascorbic acid is directly dependent. Similarly, the deleterious effect of
      variables such as oxygen and pH are influenced by temperature. Therefore, low
      temperature storage is imperative in order to regard L-ascorbic acid delay. A
      definite role of amino acids in L-ascorbic acid degradation has not been
      identified.

PMID- 7621083
TI  - Reproducibility of a semiquantitative food frequency questionnaire to assess the
      intake of fats and cholesterol in The Netherlands.
AB  - The reproducibility of a 104 item semiquantitative food frequency questionnaire
      to estimate the intake of energy, fat, fatty acids and cholesterol was assessed
      in a group of 93 men and women in the Netherlands. The questionnaire was
      administered by trained interviewers. Subjects were asked to recall the
      consumption of 104 items during the past month. A second interview was conducted
      8 weeks later. The mean difference in nutrient intake between the two assessments
      was very small, with a maximum of 5% for cholesterol intake, but the variance of
      individual differences was considerable. Pearson correlation coefficients between
      two assessments 8 weeks apart ranged from 0.71 for polyunsaturated fatty acids
      intake (when expressed as percentage of energy intake) up to 0.91 for energy
      intake. The reproducibility was found to be similar in males and females.
      Reproducibility was assessed for separate food items as well as for 20 food
      groups. Items consumed were often highly reproducible and rarely had a poor
      reproducibility. This food frequency questionnaire is considered to be a suitable
      tool to estimate and monitor the intake of fat, fatty acids and cholesterol in
      the Netherlands.

PMID- 7621084
TI  - Reducing cassava toxicity by heap-fermentation in Uganda.
AB  - Processing of cassava roots by the Alur tribe in Uganda includes a stage of solid
      substrate fermentation in heaps. Changes in cyanogen levels during the process,
      microflora involved, and protein levels, amino acid patterns and mycotoxin
      contamination of the final products were studied. Processing was monitored at six
      rural households and repeated at laboratory site, comparing it to sun-drying.
      Flour samples from rural households were analysed for residual cyanogens,
      mutagenicity, cytotoxicity and aflatoxins. Mean (+/- SD) total cyanogen levels in
      flours collected at rural households were 20.3 (+/- 16.8) mg CN equivalents kg-1
      dry weight in 1990 (n = 23) and 65.7 (+/- 56.7) in 1992 (n = 21). Mean (+/- SD)
      levels of cyanohydrins plus HCN were 9.1 (+/- 8.7) in the 1992 flours. Total
      cyanogen levels in the village monitored batches were reduced considerably by
      heap-fermentation from 436.3 (+/- 140.7) to 20.4 (+/- 14.0) mg CN equivalents kg
      1 dry weight cassava. Residual cyanogen levels were positively correlated with
      particle size of the resulting crumbs. Heap-fermentation was significantly more
      effective in reducing cyanogen levels than sun-drying alone, but did not always
      result in innocuous levels of of cyanogens. Dominant mycelial growth was from the
      fungi Neurospora sitophila, Geotrichum candidum and Rhizopus oryzae. No
      mutagenicity, cytotoxicity nor aflatoxins could be detected in the flours.
      Protein quantity and quality were not significantly reduced. Cassava gel
      viscosity pattern was modified to the consumers' preference by this method. As
      the removal of cyanogens was more efficient and we found no new obvious health
      risk, heap-fermentation can be regarded as an improvement compared to sun-drying
      alone in areas where cassava varieties with higher cyanogen levels prevail, but
      we recommend optimisation of the process for ensuring still safer products.

PMID- 7621086
TI  - Variation of iron, copper, free fatty acid content and lipoxygenase activity in
      peanut kernels subjected to various pretreatments and roasting.
AB  - Peanut kernels subjected to pretreatment including rehydration, blanching and
      dehydration, and untreated kernels were roasted at 160 degrees C for times
      ranging from 0 to 90 min. For both peanuts, the iron content in oil and specific
      lipoxygenase activity in defatted peanut flour decreased, free fatty acid content
      increased and copper content changed insignificantly with roasting time. Changes
      of iron content, lipoxygenase activity and free fatty acid content were more
      significant in untreated peanuts than in pretreated peanuts. At each roasting
      time, iron, copper and free fatty acid contents in the oils and lipoxygenase
      activities in the defatted flours prepared from untreated peanuts were higher
      than in the oils and flours prepared from pretreated peanuts.

PMID- 7621085
TI  - Dietary assessment of a group of elderly Spanish people.
AB  - The dietary patterns of 60 elderly from Spain (37 women and 23 men) were examined
      by analysis of the food, energy and nutrient intake during 5 days. The caloric
      profile was somewhat unbalanced, since the percentage of total energy intake from
      proteins and lipids was above the recommended limit whereas the proportion of
      energy derived from carbohydrates was slightly deficient. The degree of
      underreporting derived by subtracting predicted total daily energy expenditure
      from self-reported energy intake obtained from a diet control during 5 days is
      120 kcal/day in men and 334 kcal/day in women. More than 50% of the population
      showed intakes of pyridoxine, folates, vitamin A (only in men), vitamin D,
      vitamin E. zinc, magnesium and iron (only in women) lower than those recommended.
      Although it is likely that the real intakes of these micronutrients are higher
      than the levels measured considering the underreporting, the obtained results
      show the existence of a risk of deficiency of several nutrients. An increase in
      the energy intake of the group with a parallel increase in physical activity with
      a view to avoiding weight gain may be of use in improving the nutritional status
      of the group. This measure, together with increased consumption of vegetables and
      milk products especially, may lead to a striking reduction in illness, a finding
      that is of considerable clinical and public health importance.

PMID- 7621087
TI  - Evaluation of the selenium content of the traditional Italian diet.
AB  - Food samples and ready-made meals from the traditional Italian-type diet were
      analysed for selenium content. The average Se content varied in food samples from
      7 micrograms/kg w/w (fresh fruit) to 226 micrograms/kg w/w (fish). The highest
      average contents were obtained in the animal products and in legumes. Among ready
      made foods the animal derived dishes were the richest in Se, representing 78% of
      the estimated total daily dietary intake of Se. The average daily dietary intake
      of selenium for Italian people is estimated to be 50.9 +/- 29.8 micrograms Se/day
      when results obtained on complete meals are used, while it is 45.0 +/- 30.8
      micrograms Se/day when results on foods and statistical data on consumption are
      used.

PMID- 7621088
TI  - Glycaemic response in normal subjects to five different legumes commonly used in
      the Philippines.
AB  - Five legumes including chick pea (Cicer arietinum Linn), pigeon pea (Cajanus
      cajan Linn. Huth.), black bean (Phaseolus vulgaris Linn), mung bean (Phaseolus
      areus Roxb) and white bean (Phaseolus vulgaris Linn) were cooked and tested for
      blood glucose response among healthy human volunteers. The blood glucose response
      to all legumes was significantly lower compared to bread. The glycaemic response
      to chick pea was significantly lower (P < or = 0.01) than that to black bean,
      pigeon pea and mung bean. The glycaemic index of chick pea (13.87 +/- 3.0) was
      significantly lower than those of black bean (27.91 +/- 4.0), pigeon pea (30.99
      +/- 4.1) and mung bean (44.38 +/- 5.8) (P < 0.01) but was not different from that
      of white bean (19.48 +/- 4.9). The differences in the glycaemic responses among
      the legumes could be due to the differences in amount and kind of dietary fibre,
      amylose content and the presence of antinutrients. Legumes could therefore be
      added to the list of foods for diabetics and hyperlipidaemics and continuous
      consumption in larger amounts should be recommended to the general Filipino
      population.

PMID- 7621089
TI  - Nutritional and dental implications of high and low intakes of sugar.
AB  - Currently, in nutrition there are major anxieties over the bearing of high
      intakes of energy and certain nutrients (e.g. fat, sugar) on health/ill-health.
      Two questions concern sugar: does a high intake (1) cause a deleterious imbalance
      or dilution of macro- and micro-nutrients? and (2) does it promote degenerative
      diseases, in particular dental caries? As to the first question, evidence from a
      variety of contexts indicates that nutrient intakes are not reduced; rather they
      are increased. Additionally, one accompaniment of a high sugar intake is a
      reduced intake of fat, one of the primary aims of nutritional guidelines.
      However, these do not license excessive sugar consumption. As to sugar and
      degenerative diseases, evidence is lacking that sugar intake is significantly
      influential other than for dental caries. An examination of evidence indicates
      sugar consumption to be a weak factor in caries development; its intake explains
      little of the variance in caries occurrence. Clearly, additional factors are
      influential-genetic, exposure to fluoride, and dietary components other than
      sugar. Early detection of the relatively small proportion of caries-prone
      individuals by appropriate markers, must be sought.

PMID- 7621090
TI  - Trans fatty acids: a cause for concern?
AB  - The recommendation to reduce total and saturated fat is incorporated into the
      dietary guidelines for the general population in many western countries. In
      addition, dietary modification to reduce substantially the intake of saturated
      fats is a cornerstone of treatment in the hyperlipidaemias. Concern has recently
      been expressed regarding possible deleterious effects of trans isomers of
      unsaturated fatty acids on the lipoprotein profiles of both normo and
      hypercholesterolaemic persons. This review seeks to examine recent research in
      this area with a view to considering possible changes in the present dietary
      recommendations.

PMID- 7621091
TI  - Effect of stabilisation treatment of rice bran on nutritional quality of protein
      concentrates.
AB  - Protein concentrates were prepared from unstabilised, acid stabilised, heat
      stabilised and parboiled rice bran, either freeze dried or roller dried. They
      were assessed for their nutritional quality by both in vivo and in vitro assays.
      The essential amino acid profile of protein concentrates was comparable to rice
      proteins or rice bran proteins as such. Limiting amino acids of concentrates were
      threonine and isoleucine. Essential amino acid indices for different samples
      ranged from 72.4 to 77.6. Lysine content was high (4.32-5.55 g/16 g N) of which
      52-57% was available. Freeze dried protein concentrate from untreated and acid
      stabilised rice bran exhibited very high in vitro digestibility (84.1 and 86%,
      respectively) whereas protein concentrates from heat stabilised and parboiled
      rice bran had lower digestibility of 57.3 and 61.2%, respectively. Roller dried
      samples from untreated and acid stabilised rice bran showed high digestibility
      with pepsin and pancreatin but low value with pepsin, indicating effect of heat
      on pepsin digestibility. The results of animal assays can be summarised as
      follows. The PER values of diets based on protein concentrates from untreated and
      acid stabilised rice bran at 10% protein level were 2.16 and 2.34 and at 15%
      protein level were 2.20 and 2.11, respectively. Net protein ratio and nitrogen
      utilisation from both protein concentrates were also high and not significantly
      different from the standard protein.

PMID- 7621092
TI  - Pharmacology of neuromuscular blockade: interactions and implications for
      concurrent drug therapies.
AB  - Neuromuscular blocking agents (NMBAs) have historically been utilized in the
      operating room as an adjunct to general anesthesia to induce skeletal muscle
      relaxation. Within the past decade, their use has been extended to the intensive
      care setting to facilitate tracheal intubation, provide paralysis in patients
      unable to tolerate mechanical ventilation, or aid in the management of
      ventilatory failure. Numerous factors must be considered when selecting a
      potential NMBA for use: speed of onset, route of elimination, potential for
      adverse effects (cardiovascular or histamine release), potential for "cumulative"
      effect, intermittent or continuous infusion administration capability, and
      potential for drug-drug interactions. This article is concerned with the
      pharmacology, pharmacokinetics, and physiology of those NMBAs that are commonly
      prescribed and their therapeutic usefulness in the treatment of the critically
      ill.

PMID- 7621093
TI  - Ethical considerations in the use of neuromuscular blockades.
AB  - The long-term use of neuromuscular blocking agents in the adult intensive care
      unit is clinically and ethically challenging. These drugs can be dramatically
      lifesaving; they also have the potential of causing the patient great emotional,
      spiritual, and physical harm. Traditional ethical analysis is important but may
      not be adequate. Rigorous attention should be given to risk-benefit ratios,
      informed consent, and quality of life. It is suggested that institutions develop
      written consent forms and information sheets, use adapted values history forms in
      assessing treatment decisions and quality of life, and fully utilize ethics
      committees and patient care conferences in caring for these catastrophically ill
      patients.

PMID- 7621094
TI  - Cardiopulmonary implications of neuromuscular blockade.
AB  - Neuromuscular blocking agents (NMBAs) are used to facilitate mechanical
      ventilation in critically ill patients. Individual NMBAs differ in their
      metabolism and elimination, side effects, and duration of action. These
      differences help designate which NMBA has the greatest efficacy, given different
      scenarios. A common theme with all NMBAs is their ability to ablate spontaneous
      breathing; hence, vigilant cardiopulmonary monitoring is warranted when NMBAs are
      used.

PMID- 7621095
TI  - Monitoring the administration of neuromuscular blockade in critical care.
AB  - The future direction of neuromuscular blockade (NMB) in critical care will be
      characterized by prudent utilization and quality monitoring. With the potential
      for persistent paralysis and less than optimal outcomes, this direction makes
      sense. Prudent utilization can be further defined as exhausting other therapies
      prior to NMB utilization. When NMB is necessary, the agents should be titrated
      consistently according to a protocol, using the minimally effective dose to
      produce the least amount of NMB in order to facilitate patient management.
      Quality monitoring requires that peripheral nerve stimulator (PNS) monitoring
      become the standard for monitoring the administration of NMB agents and also that
      monitoring be accurate. Inherent to prudent utilization and quality monitoring is
      an adequate knowledge related to all aspects of NMB. The purpose of this article
      is to provide the necessary knowledge base for practitioners to understand normal
      and altered neuromuscular junction function, perform accurate PNS monitoring, and
      titrate NMB therapy according to the individual and desired response.

PMID- 7621096
TI  - Comprehensive review: neuromuscular blocking agents in critical care.
AB  - Administration of neuromuscular blocking agents (NMBAs) in critical care units
      has become tremendously controversial. The increased use of these agents without
      a defined indication or research base has resulted in dangerous and costly
      complications and serious concerns. Areas of controversy include mounting adverse
      effects (especially prolonged paralysis and weakness from long-term overdosing),
      an inconsistent and deficient knowledge base among all levels of health care
      professionals, inadequate concurrent sedation and analgesia, and a lack of
      effective monitoring to ensure the lowest possible doses. There is a great need
      for research to define the practice and protocols that would optimize safe and
      efficacious use. Pharmacologic paralysis should be restricted to a very specific
      patient population after careful evaluation, and therapy should be discontinued
      at the earliest possible time. Chemical paralysis can be a safe and effective
      therapy for a select few patients when judicious care, multidisciplinary efforts,
      and prevention of adverse effects minimize the complications, growing costs, and
      unintended suffering.

PMID- 7621097
TI  - Neurologic function and neuromuscular blocking agents in critical care.
AB  - Neuromuscular blocking agent (NMBA) use in critical care units is generally
      reserved for life threatening situations. The goal of any life-support effort,
      including efficient mechanical ventilation, maintenance of hemodynamic stability,
      and NMBA use, is to optimize cerebral preservation. Yet, although all other organ
      systems are aggressively monitored, very little is done to assess neurologic
      stability during NMBA therapy. This article addresses the neurologic issues
      associated with NMBA use: identification of those patients at risk for a
      neurologic event; rationale for monitoring cerebral changes during paralytic
      therapy; and potential means of assessing and intervening before, during, and
      after chemical paralysis.

PMID- 7621098
TI  - Sedation and pain control in the critically ill patient maintained on continuous
      neuromuscular blockade.
AB  - Anxiety and pain pose a challenge in the management of the critically ill patient
      on continuous neuromuscular blockade. Without adequate treatment, anxiety can
      further complicate a patient's already compromised state. Benzodiazepines,
      haloperidol, and propofol provide options for anxiolysis in these patients.
      Despite the fact that the physiologic consequences of pain can be devastating,
      the undertreatment of pain remains an issue. The opioid agonists constitute the
      agents of choice for parenteral analgesia in the critically ill.

PMID- 7621099
TI  - Efficacy of low-dose GnRH analogue (Buserelin) in the treatment of hirsutism.
AB  - The aim of the present study was to evaluate the effect of low dose GnRH analogue
      (Buserelin) on gonadal steroid secretion and hair growth in hirsute women. The
      drug was administered as a nasal spray (200 micrograms tid) to reduce gonadal
      steroid secretion. Eight hirsute women were treated for six month with the
      gonadotropin-releasing hormone analog. All had subclinical polycystic ovary
      syndromes on the basis of ultrasound or hormonal data, together with ovary
      dysfunctions and irregular menses. None had adrenal or pituitary dysfunction. The
      score of hirsutism was evaluated according to Ferriman and Gallway; pituitary
      function was evaluated measuring the FSH and LH response to GnRH stimulation and
      gonadal steroid secretion by measuring estradiol, progesterone, total plasma
      testosterone, androstenedione and androstanediol. Sex hormone binding globulin,
      insulin, prolactin and DHEA-S were also measured. The suppression of ovarian
      steroid secretion was confirmed by reductions in total plasma testosterone, and
      rostenedione and androstanediol that were detectable after one month of
      treatment. FSH and LH responses to GnRH stimulation were inhibited consistent
      with pituitary desensitization. No significant side effects were observed and all
      patients completed the trial. The score of hirsutism was 24 +/- 5 before, 19.6 +/
      6 by the 3rd month and 16.8 +/- 5.1 by the 6th month of treatment (p < 0.001);
      the effect was still evident 1 and 6 months after the withdrawal of the therapy
      (14.8 +/- and 15.8 +/- 5 respectively; p < 0.001). Our findings indicate that
      Buserelin is useful in the treatment of non adrenal hirsutism when other forms of
      therapy are contraindicated or poorly tolerated by the patient.

PMID- 7621100
TI  - Growth hormone binding to a circulating receptor fragment--the concept of
      receptor shedding and receptor splicing.
AB  - Recent advances in the understanding of circulating growth hormone binding
      proteins (GHBP) are reviewed. The high affinity GHBP represents the ectodomain of
      the GH receptor (GHR); it is either cleaved from membrane-bound GHRs (man,
      rabbit) or derived from an alternatively spliced GHR mRNA (rodents). Another
      circulating GHBP, of low affinity and not GHR-related, is only partially
      characterized. The GHBPs complex about half of the GH in human plasma. They act
      as a buffer regulating free and bound GH, prolong GH half-life, and modulate GH
      bioactivity through competition with GHRs for ligand. The plasma levels of both
      GHBPs are developmentally upregulated during childhood and remain relatively
      constant thereafter. Different species vary in their regulation of GHBP, with
      sexual dimorphism and large pregnancy-related changes in some but not all
      species. A variety of conditions associated with altered GH responsivity
      (resistance or hypersensitivity) are attended by altered levels of the high
      affinity GHBP. Generally, GH resistance is characterized by decreased GHBP
      levels, and the converse is true in GH hypersensitivity such as in obesity. It
      has been postulated that the plasma GHBP level reflects tissue concentrations of
      the GHR, but this remains to be proven. The high affinity GHBP appears to be
      positively, though imperfectly, linked to GH action. Soluble receptor isoforms
      analogous to the GHBP have been demonstrated for several members of the cytokine
      receptor family to which the GHR belongs. The ultimate biological role of these
      circulating receptor ectodomains remains to be fully defined.

PMID- 7621101
TI  - Hormonal response of primary hepatocytes of the clawed toad, Xenopus laevis.
AB  - Freshly isolated hepatocytes of the clawed toad, Xenopus laevis, were cultured
      for at least 3 days. The viability of the cells was characterized using staining
      and biochemical methods. In particular, the glucose and glycogen balance was
      tested. After culture for 16-20 hrs, the cells were subjected to hormonal
      treatment. Both adrenaline and arginine vasotocin stimulated the release of
      glucose in a dose dependent manner. 10(-6) M concentrations were strongly
      effective. The determination of the glycogen balance made it clear that the
      glucose release is mainly due to glycogenolysis. Using receptor antagonists and
      agonists, it has been shown that the effect of adrenaline is clearly mediated by
      beta-type receptors. Arginine vasotocin stimulated glycogenolysis via a type of
      receptor which is similar to the V2-receptor of mammals. This means that cAMP is
      involved in the response to both types of hormones which is in contrast to that
      which is known about the effect of nonapeptides on the liver of mammals.

PMID- 7621102
TI  - Gynaecomastia in a patient with a hCG producing giant cell carcinoma of the lung.
      Case report.
AB  - Gynaecomastia, or enlargement of the male breast may result from various
      endocrine dysfunctions and often reflects ectopic production of substances such
      as hCG and estradiol. We report on the case of a 30 year old man who presented
      with gynaecomastia and elevated plasma levels of hCG, estradiol and testosterone.
      As a result of several diagnostic procedures such as selective venous sampling
      and magnetic resonance tomography (MRT), a hCG producing tumor of the upper lobe
      of the left lung was found. This hormonal overproduction induced an enhanced
      secretion of estradiol and testosterone in the testicular tissue. Histology
      revealed a giant cell carcinoma with positive immunostaining for hCG. This case
      report further underlines the necessity of an intensive search for ectopic beta
      hCG production due to malignant tumours, in particular in the adult.

PMID- 7621103
TI  - Characteristics of pulsatile and circadian prolactin release and its variability
      in men.
AB  - In order to investigate the intra- and interindividual variability of spontaneous
      prolactin (PRL) secretion, 24 h blood sampling at 10 min intervals was performed
      in ten healthy young men (age 19 to 25 yrs) on three occasions (intervals 2 weeks
      and 3 months). Plasma PRL concentrations were determined in duplicate by
      immunoradiometric assay. Peak detection was carried out with the PULSAR program.
      The circadian rhythm was analyzed by a complex cosinor method combining
      fundamental (24 h), 1st harmonic (12 h), and 2nd harmonic (6 h) frequencies. The
      original data was well represented by this calculation as shown by mean (+/- SD)
      correlation coefficients of 0.84 +/- 0.08. Mean and integrated PRL concentrations
      showed the lowest intraindividual variability (range 2.8 to 19.6%) of all
      parameters tested. For the number of peaks per 24 h, a median intraindividual
      variability of 24.2% (range 6.9 to 50%) was seen. In general, intraindividual
      variability of parameters of pulsatile PRL release was lower than the variability
      between subjects. The complex cosinor analysis revealed a bimodal pattern of PRL
      secretion in most profiles. Acrophases (times of highest PRL levels) were found
      between 0040 and 1000 h, nadirs between 0030 and 2300 h. The amplitude of the
      circadian rhythm (Max-Min) ranged from 3.8 to 16.9 ng/ml. The time lag between
      onset of sleep and acrophase was variable (1.75 to 7.38 hrs). Variability of
      nadir, minimal and maximal PRL, amplitude, and minimal PRL as percent of the
      mesor was significantly lower within individuals than between subjects (p <
      0.02). During sleep, peak heights and peak amplitudes were significantly higher
      than during waking periods (p < 0.004). No statistically significant differences
      were found in the distribution of relative frequencies of peak number, peak
      amplitudes and peak heights between the three series of profiles. The
      distribution of peak heights was compatible with a normal distribution. In
      conclusion, it was shown that the circadian rhythm of PRL secretion in normal men
      can be analysed accurately and reliably with the complex cosinor method, which is
      relatively easy to perform and yields results comparable to those obtained by
      much more complicated programs.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7621104
TI  - Distribution and cycle phase dependency of gonadotropin receptors in musculature
      and blood vessels of the porcine broad ligament.
AB  - Luteinizing hormone (LH) and human chorionic gonadotropin (hCG) share common
      receptors in the uterus of many species. The aim of the present work was to
      investigate the possibility of LH/hCG binding sites present in the musculature of
      the porcine broad ligament, and to study the topography of LH/hCG receptors in
      ligamental blood vessels. Uteri of cyclic pigs were collected during follicular
      (n = 6) and midluteal (n = 6) phases of the estrous cycle. The horns and broad
      ligaments were dissected for measurements of numbers and affinities of unoccupied
      LH/hCG binding sites in crude cell membrane fractions of the myometrium and the
      smooth muscle layers of the ligament. The tissue samples for contact
      autoradiography, on film using [125I]hCG as ligand, were collected from different
      regions of the reproductive tract including: ovary, uterine horn, paraovarian
      vascular plexus, uterine vein, and uterine artery with supplying vessels and the
      outer arches of the broad ligament. The kidney and liver were used as negative
      control tissue. The specific binding of [125I]-labelled hCG in blood vessels was
      quantified on the base of optical density of the film. Scatchard analysis of data
      from broad ligamental and myometrial crude membrane preparations gave comparable
      estimates of the association constants and numbers of LH/hCG receptors. Mean
      concentrations (+/- SEM) of receptors (nmol/kg protein) were lower in the broad
      ligament than in the myometrium (p < 0.05) during both follicular and luteal
      phases (2.2 +/- 0.5 vs. 1.0 +/- 0.3 and 2.5 +/- 0.5 vs 1.7 +/- 0.2;
      respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7621106
TI  - Hepatocyte growth factor gene expression after massive small bowel resection:
      lack of stimulation in lung and liver.
AB  - Both hepatic and renal regeneration are associated with rapid increases in
      hepatocyte growth factor (HGF)mRNA levels, not only in the regenerating tissue,
      but also in the lung. In this study, changes in the levels of HGF mRNA in the
      terminal ileum and also in distal organs in the rat following massive small bowel
      resection (MSBR) have been investigated with a sensitive S1 nuclease assay. HGF
      mRNA levels are low in the ileum and increase only transiently post-MSBR. In
      contrast to the other models of regeneration, no increase in HGF mRNA levels is
      observed in the lung nor in kidney and liver post-MSBR. This suggests that the
      ileum does not release "injurin", the putative humoral mediator of the response
      of the lung observed after hepatectomy or nephrectomy.

PMID- 7621105
TI  - No effect of ethinylestradiol treatment on melatonin secretion in healthy
      pubertal girls.
AB  - The present study investigated the impact of high estrogen doses on melatonin
      blood concentrations in healthy young girls. Melatonin secretion was investigated
      in 7 girls (chronological age 13.2 +/- 0.2 years; bone age 12.8 +/- 0.2 years)
      before and during treatment with ethinylestradiol (EE2, daily dose 0.5 mg/d
      orally) aimed at the reduction of final prospective height in familial tall
      stature. Melatonin, LH, FSH, E2 and EE2 were measured by radioimmunoassay. In all
      subjects, LH and FSH were completely suppressed, but melatonin secretion,
      day/night plasma values as well as the area under the curve (AUC) remained
      unchanged under pharmacological administration of ethinylestradiol. We therefore
      conclude that melatonin secretion is not affected by pharmacological doses of the
      synthetic estrogen derivative ethinylestradiol in healthy young girls. The
      decrease of melatonin blood concentrations during puberty is not caused by
      increasing concentrations of estrogens but must be due to some other process.

PMID- 7621108
TI  - The Mabel Liddiard Memorial Lecture, 1994. Changing childbirth: would Mabel
      Liddiard approve?

PMID- 7621107
TI  - Diabetic microvascular complications and growth factors.
AB  - Diabetes mellitus is associated with typical patterns of long term vascular
      complications which vary with the organ involved. The microvascular kidney
      disease (Olgemoller and Schleicher, 1993) is characterized by thickening of the
      capillary basement membranes and increased deposition of extracellular matrix
      components (ECM), while loss of microvessels with subsequent neovascularisation
      is predominant in the eye and peripheral nerves. On the other hand macrovascular
      disease is characterized by accelerated atherosclerosis. These complications are
      dependent on long term hyperglycemia. Specific biochemical pathways linking
      hyperglycaemia to microvascular changes were proposed: the polyol pathway (Greene
      et al., 1987), non-enzymatic glycation of proteins (Brownlee et al., 1988),
      glucose autooxidation and oxidative stress (Hunt et al., 1990), hyperglycemic
      pseudohypoxia (Williamson et al., 1993) enhanced activation of protein kinase C
      by de novo-synthesis of diacyl glycerol (Lee et al., 1989; DeRubertis and Craven
      1994) and others. These pathways are not mutually exclusive (Larkins and Dunlop,
      1992; Pfeiffer and Schatz, 1992). They may be linked to alterations in the
      synthesis of growth factors particularly since atherosclerosis and
      angioneogenesis are associated with increased proliferation of endothelial and
      smooth muscle cells. Increased synthesis of ECM components is stimulated by
      growth factors like transforming growth factor beta (TGF beta) (Derynck et al.,
      1984) and insulin-like growth factor I (IGF-I) (Moran et al., 1991). This review
      will summarize some of the recent evidence for an involvement of growth factors
      in diabetic vascular complications and will attempt to assign their emergence in
      the sequence of events leading to vascular complications.

PMID- 7621109
TI  - Good communication--moving towards a "changing childbirth" objective.

PMID- 7621110
TI  - Choice & control: a midwife's view.

PMID- 7621111
TI  - Giving vitamin K to newborn babies in the SCBU.

PMID- 7621113
TI  - International Midwives Congress for the Francophone World.

PMID- 7621112
TI  - Computerisation of infusion calculations in neonatal intensive care.

PMID- 7621114
TI  - UKCC Working Conference on Supervision of Midwifery.

PMID- 7621115
TI  - Artificial rupture of the membranes in spontaneous labour.

PMID- 7621116
TI  - Maternal and child health: international resolutions.

PMID- 7621117
TI  - Caring for mother & baby. Taking care of your baby's skin.

PMID- 7621118
TI  - Women's experience of maternity care in an inner city: a team-based qualitative
      study.

PMID- 7621119
TI  - An inner urban funded maternity care programme.

PMID- 7621120
TI  - Term PROM.

PMID- 7621121
TI  - Standing up for midwives: introducing the RCM's Employment Affairs Committee.

PMID- 7621122
TI  - Caring for mother & baby. Taking care in the sun.

PMID- 7621123
TI  - Midwifery--a profession of change.

PMID- 7621124
TI  - Serum screening for Down's syndrome.

PMID- 7621125
TI  - Smoking and the pregnant woman.

PMID- 7621126
TI  - Ethics & midwifery practice.

PMID- 7621127
TI  - A personal view of a midwifery development unit.

PMID- 7621128
TI  - The progress of physiological anthropology in Japan.

PMID- 7621129
TI  - The relationships between lumbar curves, pelvic tilt and joint mobilities in
      different sitting postures in young adult males.
AB  - The lumbar lordosis and pelvic tilt of twenty male subjects were measured in
      standing and in three different sitting postures with the trunk-thigh angles of
      120 (sitting A), 90 (sitting B), and 60 (sitting C) degs and the knee angle was
      constant at 90 deg. Ten more male subjects participated in the supplemental
      study, in which additional condition of the knee angle was employed in postures
      of the trunk-thigh angles of 90 and 60 degs. Some joint mobilities were also
      measured to investigate the relations of the mobilities to lumbar lordosis and
      pelvic tilt. The lumbar curve decreased and the pelvis rotated rearward
      significantly as the trunk-thigh angle and the knee flexion decreased. The great
      alteration of the lumbar curve was observed between standing and sitting A, which
      was much different from the results of Keegan (1953) studied in the subjects of
      lateral recumbent position. There was a high correlation coefficient between the
      lumbar curve and the pelvic tilt (r = 0.909), so that the relations of the pelvic
      tilt to the joint mobilities were investigated. When the knee angle was constant,
      the pelvic tilt is related significantly to the hamstrings between standing and
      sitting A and to the gluteus maximus between sitting A and sitting C. However, at
      different sitting postures with the trunk-thigh angles of 90 and 60 degs
      involving different knee flexions, hamstrings added to gluteal muscles affected
      significantly lumbar curve and pelvic tilting.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7621130
TI  - Thermal responses of 6- to 8-year-old children during immersion of their legs in
      a hot water bath.
AB  - Twenty-three children (12 boys and 11 girls) and 13 female students served as the
      subjects in summer. The children were from six to eight years old. The subjects
      were seated in a hot room of 30 degrees C and their legs were immersed in bath
      water of 42 degrees C for 30 minutes. Total sweat rate, local sweat rate on the
      back, rectal temperature, skin temperatures at eight sites, heart rate and blood
      pressure were measured during the experiments. Total sweat rate of both groups
      was similar, but local sweat rates of the children were significantly smaller
      than those of the students. Although the degree of increase in rectal temperature
      from immersion in the hot bath were similar, the increases of heart rate and skin
      temperatures on the thigh and forearm were greater in children. These results
      suggest that the thermoregulatory ability of children during heat exposure is
      similar to that of young female adults. However, it is found that for heat loss,
      children resort more to vasodilation than sweating during heat exposure as
      compared to adults. The children were divided into two groups according to
      whether the children were exposed to air cooling systems in summer in their
      infancy or not. There was no significant inter-group differences in physiological
      responses during immersion in the hot water bath. It is found that the ability of
      Japanese children to tolerate heat was not reduced distinctly by the frequent use
      of an air cooling system in infancy.

PMID- 7621131
TI  - Monitoring accumulative fatigue of finger by autoregressive modeling of
      physiological tremor.
AB  - In this study, block data structured autoregressive (AR) method is used to
      evaluate fatigue, based on physiological tremor during and after loading a weight
      mass on the index finger. The temporal changes in the prediction coefficients and
      the reflection coefficients are determined. AR spectral estimation with the ninth
      order is obtained and presented in graphical form. The results indicate that the
      first prediction coefficient a1 can be used to characterize the state of fatigue
      of finger muscle and the other prediction coefficients do not show any tendency
      for the finger load. The coefficient a1 can be applied to monitor the
      accumulative fatigue induced by the weight loading for a duration of time.

PMID- 7621132
TI  - Physiological tremor under pseudo-fraction gravity.
AB  - The effect of pseudo-fraction gravity on physiological tremor of the human finger
      (finger tremor) has been examined experimentally by immersing an index finger
      into water at different immersion levels. The pseudo-fraction gravity, gamma G,
      was established by water buoyancy at immersion level omega, G being gravitation
      acceleration and gamma between zero and unit. The nature of variations of finger
      tremor under the influence of gamma G is estimated based on FFT spectral
      analysis. It is illustrated that with a decrease in gamma, or equivalently an
      increase in omega, two dominant peaks remaining approximately constant in
      frequencies around 10Hz and 20Hz are found, while peak amplitude is decreased
      rapidly for higher peak and slowly for lower one. Theoretically the effect of
      pseudo-fraction gravity is analyzed in terms of a specific model for finger
      tremor. The experimental results presented in this paper are predicted rather
      well by two resonant modes which occurred in our model system. It is possible to
      conclude that the model, which is characterized by a pair of antagonistic muscles
      and two reflex pathways, provides an adequate quantitative description of finger
      tremor.

PMID- 7621134
TI  - The significance of physiological studies in anthropology.

PMID- 7621133
TI  - Relationship among blood lactate and plasma catecholamine levels during exercise
      in acute hypoxia.
AB  - Five male subjects performed steady exercise on a cycle ergometer at an intensity
      of 60% maximal O2 uptake (VO2max) for 6 min on three separate occasions while
      breathing gas mixtures of 12,16 or 21% O2 in N2. Expired gas fractions,
      ventilation, heart rate, arterial O2 saturation (SaO2), blood lactate (La) and
      plasma catecholamines (epinephrine: E and norepinephrine: NE) were measured. O2
      uptake (VO2) was calculated for the last minute of exercise. Blood samples were
      drawn at rest and immediately after exercise. By inspiring hypoxic gas mixtures,
      the SaO2 value decreased during exercise to 85.0 +/- 5.4 (16%) and 66.4 +/- 4.1
      (12%) from 95.0 +/- 0.1 in normoxia. VO2 during exercise was not different among
      the three conditions. Exercise-induced La accumulation was increased by hypoxia.
      E and NE during exercise were not affected by hypoxia statistically. There was a
      significant correlation between La and E (P < 0.01) and between La and NE (P <
      0.01) during exercise in the three conditions. The present findings suggest a
      relationship between glycogen metabolism and sympathoadrenal activity which
      results in an increase of plasma catecholamines during exercise in humans acutely
      exposed to hypoxia.

PMID- 7621135
TI  - Characteristics of body shape of female athletes based on factor analysis.
AB  - We examined the body shape of female athletes in comparison with female adult non
      athletes by factor analysis. The subjects were 433 adult non-athletes and 464
      athletes participating in 11 different sporting events. The physique, skinfold
      thickness and body composition of each subject were measured. The values obtained
      from non-athletes were analyzed by factor analysis, and the body shape of the
      athletes was then analyzed according to these factors. Four main factors with
      which 80 percent of total variance could be explained were body fat (Factor 1),
      mass (Factor 2), leg length to height ratio (Factor 3) and length (Factor 4), and
      were extracted from the values from non-athletes. The body shape of the athletes
      could be classified into 4 categories by cluster analysis for factor score of
      sporting events: less body fat and slim type, average type like non-athletes,
      muscular and well-balanced type, and tall and well-developed mass. Compared with
      non-athletes, female athletes for all sporting events had less body fat.
      Moreover, the athletes had a body shape suitable for their sporting events; i.e.,
      their mass, length of leg and height.

PMID- 7621136
TI  - Effects of weight load on physiological tremor: the AR representation.
AB  - The propriety of the autoregressive (AR) method as a means of processing the
      signals of physiological tremor of human finger (finger tremor) was investigated.
      Application of the Akaike's criterion demonstrated that the 15-th order AR model
      was required to describe the recordings of finger tremor. According to Burg's
      algorithm, both AR spectrum and AR parameters were estimated to study the effects
      of various weight loads on finger tremor. It was found that, (1) the amplitude of
      AR spectrum was apparently enhanced by adding the load; (2) the first prediction
      coefficient (a1) and the first reflection coefficient (rho 1) significantly
      declined by increasing the weight loads. The results were compared with the
      calculations from FFT (Fast Fourier Transform) and autocorrelation function.
      Simple physical interpretation of the AR parameters (i.e. a1 and rho 1) was
      discussed in relation with system's resonant modes.

PMID- 7621137
TI  - Tracking clinical career paths.

PMID- 7621139
TI  - Getting the word out.

PMID- 7621138
TI  - A shared vision.

PMID- 7621140
TI  - Asthma. Building a foundation.

PMID- 7621141
TI  - Asthma. Teaching what's needed. Interview by Kathy Stodart.

PMID- 7621142
TI  - Nursing the health system.

PMID- 7621143
TI  - Asthma. Living with it. Interview by Kathy Stodart.

PMID- 7621144
TI  - Asthma. Canterbury takes action.

PMID- 7621146
TI  - Walking the talk on quality.

PMID- 7621145
TI  - Dreaming about quality.

PMID- 7621147
TI  - Academic emergency medicine: insights from the past, vision for the future.

PMID- 7621148
TI  - Emergency department CK-MB: a predictor of ischemic complications. National
      cooperative CK-MB project group.
AB  - OBJECTIVE: To demonstrate that a positive CK-MB in the emergency department (ED)
      predicts an increased risk for complications of myocardial ischemia in patients
      admitted to the hospital for evaluation of chest pain. METHODS: 53 academic and
      community hospital EDs participated in this prospective observational cohort
      analysis of 5,120 patients with chest pain without ST-segment elevation on the
      initial ED 12-lead electrocardiogram. All patients were admitted for evaluation
      of chest pain in one of the participating hospitals as part of the National
      Cooperative CK-MB Project. Patients were stratified by whether or not they had an
      elevated CK-MB level in the ED. CK-MB measurements were made on ED presentation
      and two hours later. Patient medical records were reviewed for inpatient
      diagnoses--myocardial infarction (MI) or other diagnosis--and for ischemic
      complication--cardiac-related death, recurrent or delayed in-hospital MI,
      significant ventricular arrhythmias, new conduction defects, congestive heart
      failure, and cardiogenic shock. RESULTS: 369 (7.2%) of the 5,120 patients had MI.
      The proportion of patients with any complication in the MI group was 24%, while
      the complication rate in the non-MI group was 0.4%. In all patients, regardless
      of final diagnosis, the relative risk of any complication was 16.1 (95% CI 11.0
      23.6) in those with a positive ED CK-MB versus negative ED CK-MB patients.
      Similarly, the relative risk of death was 25.4 (95% CI 10.8-60.2) in positive ED
      CK-MB versus negative ED CK-MB patients. CONCLUSIONS: Multicenter data support
      the hypothesis that CK-MB measurements can help risk-stratify ED chest pain
      patients whose initial ECGs are without diagnostic ST-segment elevation.

PMID- 7621150
TI  - Access to care, controlling costs, and the Oregon health plan.

PMID- 7621151
TI  - Efficacy of audio-prompted rate guidance in improving resuscitator performance of
      cardiopulmonary resuscitation on children.
AB  - OBJECTIVE: To evaluate the effect of audio-prompted rate guidance during chest
      compressions on the performance of cardiopulmonary resuscitation (CPR) on
      children. METHODS: This 24-month prospective study occurred in the pediatric
      intensive care units of a university hospital and a children's hospital.
      Intubated children with nontraumatic cardiac arrest were eligible. After
      placement of an infrared capnometer between the endotracheal tube and
      resuscitation bag, an audiotape instructed the resuscitator to perform chest
      compressions at 100 per minute or 140 per minute for one minute, followed by
      another minute at the other rate. End-tidal carbon dioxide partial pressure
      (PETCO2) was recorded prior to audiotape instruction and after one minute of CPR
      at each rate. RESULTS: Six patients, two boys and four girls, with a mean age of
      15 +/- 13 months (range 2-36 months) were studied. All had asystole or pulseless
      electrical activity. CPR was provided for 14 +/- 9 minutes prior to institution
      of the study protocol. PETCO2 at 140/min was higher than at baseline (12 +/- 7
      torr verus 4 +/- 3 torr, p < 0.05). There was a trend towards higher PETCO2s at
      100/min compared with baseline (11 +/- 12 torr versus 4 +/- 3 torr, p = 0.08).
      PETCO2s did not differ at 100/min compared with 140/min. CONCLUSIONS: In support
      of prior adult and animal investigations suggesting that basic CPRR is often
      performed poorly and at inappropriately slow rates, audio- prompted rate guidance
      during CPR in children resulted in higher PETCO2, suggesting improved CPR
      performance.

PMID- 7621149
TI  - In-vitro comparison of bag-valve-mask and the manually triggered oxygen-powered
      breathing device.
AB  - OBJECTIVE: To determine whether tidal volume, intrapleural pressure, and gastric
      volume differ when the bag--valve-- mask (BVM) and the manually triggered oxygen
      powered breathing device (MTBD) are used in the settings of normal and decreased
      lung compliance. METHODS: Prospective, randomized in-vitro model, with emergency
      medical technician-paramedics (EMT-Ps; n = 10) and emergency medical technicians
      (EMTs; n = 20) blinded to model gauges. Each participant randomly performed four
      one-minute trials ventilating a mechanical test lung through an intubation
      mannikin head at a rate of 20 breaths/min. Each subject used the BVM and the MTBD
      to ventilate the lung for 20 breaths during normal (0.10 L/cm H2O) and decreased
      0.04 L/cm H2O) compliance. Tidal volumes and intrapleural pressures were recorded
      for every breath and the gastric volume was recorded for each trial using a
      flowmeter placed below a simulated esophageal sphincter (20 cm H2O PEEP valve).
      RESULTS: With normal compliance, mean tidal volumes and intrapleural pressures
      were not significantly different, while mean gastric volumes differed
      significantly (BVM = 1,300 mL, MTBD = 0 mL; p < 0.001). When compliance was
      decreased, mean tidal volumes and intrapleural pressures again did not differ
      significantly, while gastric volumes remained significantly different (BVM =
      3,700 mL, MTBD = 1,100 mL p < 0.001). CONCLUSIONS: In this model, tidal volumes
      and intrapleural pressures were similar for the two devices. When compliance was
      normal, no participant insufflated the stomach with the MTBD, while the gastric
      volume with BVM ventilation averaged 1.3 L. With decreased compliance, the MTBD
      again delivered significantly less gastric volume than the BVM (1.1 vs. 3.7 L,
      respectively). These findings favoring MTBD ventilation require corroboration in
      vivo.

PMID- 7621153
TI  - Substance use and alcohol abuse in emergency medicine training programs, by
      resident report. SAEM Residency Survey Task Force.
AB  - OBJECTIVE: To determine the prevalence of substance use and alcohol abuse among
      emergency medicine residents. METHOD: The study instrument was an anonymous, self
      report survey that assessed the use of 13 substances and included the CAGE
      questions for measuring alcohol abuse. The survey was administered to emergency
      medicine residents at the time of the American Board of Emergency Medicine's
      annual In-Service Examination. RESULTS: Alcohol was the substance most commonly
      used by emergency medicine residents for nonmedical reasons. Using the CAGE
      score, 4.9% of residents were classified as alcoholic and another 7.6% as suspect
      for alcoholism, rates similar to those for housestaff of all specialties as
      reported in earlier studies. Instruction related to physician impairment during
      training in their emergency medicine residency was reported by only 36% of the
      respondents. CONCLUSIONS: Emergency medicine residents report a low rate of
      illicit substance use and do not appear to misuse alcohol differently than other
      housestaff. Interpretation of these results must be tempered with the potential
      for underreporting that may occur with a voluntary self-report survey of a
      sensitive nature.

PMID- 7621152
TI  - Current status of academic emergency medicine within academic medicine in the
      United States.
AB  - OBJECTIVE: To characterize the status of emergency medicine within U.S. academic
      medical centers. METHODS: All accredited emergency medicine residency programs
      and all four-year allopathic medical schools in the United States were
      identified. Institutions were defined as academic medical centers based upon NIH
      research grant funding. These institutions were ranked using five measures of
      academic stature: a survey of medical school deans, a survey of internal medicine
      residency directors, level of research funding, characteristics of the student
      body, and an unweighted composite variable reflecting overall academic stature.
      The relationship between institutional academic stature and an empiric scale of
      institutional affiliation with emergency medicine was assessed. RESULTS: Sixty
      two institutions were designated academic medical centers. These medical schools
      captured 90% of all NIH grant monies awarded in fiscal year 1990. Twenty-six of
      87 emergency medicine residency programs (30%) were closely affiliated with one
      of these medical schools. Within academic medical centers, the presence of a
      residency or an academic department of emergency medicine was inversely
      associated with the medical school deans' ranking (p < 0.005), research rank (p <
      0.001), and composite academic rank (p < 0.001). CONCLUSION: The majority of
      emergency medicine residency programs (70%) are not closely affiliated with
      institutions receiving the bulk (90%) of NIH resources for research. Within the
      institutions receiving the majority of NIH funding, there is a quantitatively and
      statistically significant inverse association of institutional emergency medicine
      affiliation and institutional academic rank.

PMID- 7621154
TI  - Intoxicated airline pilots: a case-based ethics model.
AB  - The ethical dilemma of managing two intoxicated airline pilots who insist on
      flying a commercial plane after leaving the emergency department is presented.
      The case explores the issues surrounding duty to warn, decision-making capacity,
      breaching confidentiality, and the requirements of law. A useful ethical decision
      making model is reviewed to address the responsibility of the emergency physician
      to intervene and the options available.

PMID- 7621155
TI  - Thrombolysis in acute myocardial infarction following prolonged cardiopulmonary
      resuscitation.
AB  - Thrombolytic therapy was administered to a 64-year-old man with an acute
      anterolateral myocardial infarction who had received cardiopulmonary
      resuscitation (CPR) for 24 minutes. At the time of thrombolytic therapy, the
      patient was alert and without clinical or radiographic evidence of injury. The
      patient developed a retroperitoneal hematoma related to femoral line placement,
      as well as subcutaneous bruising of the anterior chest wall; both were self
      limited. No long- term morbidity developed, and the myocardial infarction was
      aborted. The use of thrombolytic therapy for patients with acute myocardial
      infarction who have received CPR is reviewed. In the absence of clinical or
      radiographic evidence of trauma from CPR, patients with acute myocardial
      infarction should not be excluded from receiving thrombolytic therapy solely
      because of having had CPR or the duration of CPR.

PMID- 7621156
TI  - Retropharyngeal and bowel hematomas in an anticoagulated patient.
AB  - As the indications for oral anticoagulation therapy increase, the number of
      patients being treated with anticoagulants and at risk for complications also
      will rise. Major bleeding episodes have been reported to occur in approximately 2
      4% of patients being treated with oral anticoagulants. The case report of a
      patient with concurrent spontaneous retropharyngeal and small-bowel hematomas
      from overanticoagulation with warfarin is presented. The authors review the
      subtle presentation of retropharyngeal hematomas, common medications that may
      enhance warfarin anticoagulation, and therapy of potentially life-threatening
      hematomas. Airway management and possible surgical therapies to treat the
      complications of hematomas are discussed. Depending upon the indication for the
      initial anticoagulation, interim anticoagulation with heparin may be indicated.

PMID- 7621157
TI  - Birth, or benchmark of evolution?

PMID- 7621158
TI  - Can money and morality mix in medicine?
AB  - The escalation of health care costs in the United States has become a problem now
      that business and taxpayers are paying larger shares of these costs. Many believe
      that the only way to cope with rising costs is to institute explicit rationing of
      access to health care services. Proposals to ration based upon age, "sin"
      exclusions, physician gatekeeper incentives, patient ability to pay, and
      community values all have shortcomings. An alternative approach to controlling
      costs that emphasizes efficiency by cutting administrative and malpractice
      overhead costs and universally providing those medical services that have proven
      patient benefit is proposed. Physicians must take a more active role in the
      debate to ensure that patient needs are met and that expenditures are directed
      toward effective therapies.

PMID- 7621159
TI  - Early CK-MB elevations predict ischemic events in stable chest pain patients.
AB  - OBJECTIVE: To demonstrate that creatine kinase-MB fraction (CK-MB) elevations
      within three hours of presentation in the emergency department (ED) are
      associated with subsequent ischemic events in clinically stable chest pain
      patients. METHODS: Prospective cohort study at two university- affiliated
      teaching hospitals. Participants were consenting ED chest pain patients 25 years
      old or older without evidence of rhythm or hemodynamic instability (n = 449).
      Exclusions included ST-segment elevation > or = 0.1 mV in > or = 2
      electrocardiogram leads, chest wall trauma, abnormal x-ray studies, and
      incomplete data collection. Measurements included presenting and three-hour CK-MB
      levels, presenting ECG, initial clinical impression of coronary care unit need,
      and clinical follow up. Monitored adverse events included myocardial ischemia
      necessitating coronary angioplasty or cardiac bypass surgery, recurrent in
      hospital myocardial infarction, bradycardia requiring pacing, emergent
      cardioversion, cardiogenic shock, ventricular fibrillation, and death. RESULTS:
      Overall, nine (2%) of 449 patients experienced an ischemic event within the first
      48 hours. All nine patients required either coronary angioplasty or bypass
      surgery. Four (44%) of the nine patients with 48-hour ischemic events had
      elevated CK-MB levels. Of 23 patients who had complications within one week of ED
      presentation, seven (30%) had elevated ED CK-MB levels. An elevated CK-MB level
      was associated with an ischemic event both within 48 hours (risk ratio 9.5; 95%
      CI 2.7-33.7) and within one week (risk ration 5.2; 95% CI 2.3-11.7). CONCLUSIONS:
      An elevated CK-MB level within three hours of ED presentation is associated with
      a subsequent ischemic event in the clinically stable chest pain patient without
      ST-segment elevation. However, the ED CK-MB identifies only a minority or
      otherwise low-risk patients who develop ischemic events; other markers for
      diagnosing myocardial ischemia in the ED are needed.

PMID- 7621160
TI  - Emergency-department diagnosis of acute myocardial infarction and ischemia: a
      cost analysis of two diagnostic protocols.
AB  - OBJECTIVE: To assess the potential cost savings of the emergency-department (ED)
      diagnosis of acute myocardial infarction (AMI) and other myocardial ischemia
      using a nine- hour ED evaluation protocol. METHODS: This one-year study of chest
      pain evaluation unit (CPEU) patient charges was undertaken at two midwestern
      urban university hospital EDs. Included in the study were 447 patients presenting
      to the EDs with chest pain consistent with myocardial ischemia, nondiagnostic
      electrocardiograms (ECGs), and stable vital signs. Following initial ED
      evaluation, CPEU patients underwent nine hours of continuous ECG ST-segment
      monitoring with serum CK-MB levels determined at zero, three, six, and nine
      hours. Nonrandomized concurrent chest pain patients with routine ED evaluation
      and hospital admission without CPEU workup served as controls. At Center 1,
      patients with negative CPEU evaluations underwent immediate echocardiography
      (echo) and graded exercise testing (GXT) followed by ED release (CPEU;REL). At
      Center 2, CPEU patients were released from the ED for outpatient stress thallium
      testing (CPEU;REL). At Center 2, CPEU patients with positive workups as indicated
      by elevated CK-MB levels, ischemia by ST-segment monitoring, or positive
      echo/GXT/ stress thallium testing were admitted to the hospital for further
      testing. Control patients were admitted directly to the hospital to evaluate for
      AMI. Hospital charges for CPEU and control groups were compared. RESULTS: (Total
      charges in dollars, mean +/- SD, student's t-test): [table: see text] CONCLUSION:
      At both centers, hospital charges related to the acute evaluation of chest pain
      were significantly lower with this ED diagnostic protocol for AMI and myocardial
      ischemia.

PMID- 7621161
TI  - Survey of follow-up systems in emergency medicine residencies: analysis and
      proposal.
AB  - OBJECTIVE: For educational purposes, the Residency Review Committee for Emergency
      Medicine requires that emergency medicine residencies "provide a mechanism for
      each resident to obtain information on outcomes of patients the resident has
      evaluated in the emergency department." The authors analyzed the current patient
      follow-up systems of emergency medicine residencies and, based upon survey
      results propose a comprehensive organized system of follow-up. METHODS: The 84
      emergency medicine residency directors listed in the 1991 Society for Academic
      Emergency Medicine Handbook were polled regarding the current follow- up systems
      at all hospitals affiliated with their residencies. The survey contained 11
      items, including two five-point Likert scales for rating system effectiveness and
      satisfaction. A description of each hospital's follow-up system was requested,
      and other comments were reviewed. RESULTS: The 72 (86%) respondents represented
      residencies with a total of 138 affiliated hospitals, of which 89 (64.5%) had
      formal follow-up systems. Of those 89 hospitals, 39% (n = 80) residency directors
      reported that fewer than half of their residents used the systems, 63% (n = 87)
      had mandatory compliance policies; 53% had the capability for residents to obtain
      discharge summaries on admitted patients; and 66% (n = 83) had mechanisms for
      follow-up of patients released from the emergency department. Twenty-three
      percent of the systems were considered effective, with ratings of 4 or higher and
      only 31% received satisfaction ratings of 4 or more. CONCLUSIONS: Most emergency
      residency-affiliated hospitals in our survey had follow-up systems in place. Of
      existing systems, only a minority were rated by residency directors as effective
      or satisfactory. A model for a comprehensive system of patient follow-up is
      proposed.

PMID- 7621162
TI  - Ethics and health care reform.

PMID- 7621163
TI  - Medical toxicology training and certification.

PMID- 7621164
TI  - Therapy for toxicologic emergencies.

PMID- 7621165
TI  - Pediatric emergency medicine comes of age.

PMID- 7621166
TI  - Emergency medical services.

PMID- 7621168
TI  - Cardiopulmonary resuscitation.

PMID- 7621167
TI  - Disaster medicine: advances in local catastrophic disaster response.

PMID- 7621169
TI  - Pre-hospital management of acute myocardial infarction.

PMID- 7621171
TI  - Emergency decision making.

PMID- 7621170
TI  - Diagnosis of myocardial ischemia and infarction.

PMID- 7621172
TI  - Ultrasonography in emergency medicine.

PMID- 7621173
TI  - Observation medicine.

PMID- 7621174
TI  - Management of asthma.

PMID- 7621175
TI  - Acute injury care.

PMID- 7621176
TI  - Resuscitation of victims of acute hemorrhage.

PMID- 7621177
TI  - Violence in emergency facilities.

PMID- 7621178
TI  - Injury control.

PMID- 7621179
TI  - Alcohol use and trauma.

PMID- 7621180
TI  - Head injury.

PMID- 7621181
TI  - Management of animal bites.

PMID- 7621182
TI  - Infectious diseases: antimicrobial therapy.

PMID- 7621183
TI  - Wilderness medicine.

PMID- 7621184
TI  - Acute pain management.
AB  - Analgesic regimens should be based on sound clinical data and tailored to the
      individual patient's needs. The combination of specific agents for selected
      syndromes and traditional analgesics allows safe pain relief to be achieved for
      most emergency patients.

PMID- 7621185
TI  - Geriatric emergency care.

PMID- 7621187
TI  - Information technologies for emergency medicine.

PMID- 7621186
TI  - Quality-related programs.

PMID- 7621188
TI  - Undergraduate emergency medicine education.

PMID- 7621189
TI  - Survey of airway management in emergency medicine residences.

PMID- 7621190
TI  - On the electrocardiograms of young adults: primum non nocere.

PMID- 7621191
TI  - Physician workforce reform and graduate medical education reallocation: potential
      impact on emergency medicine.

PMID- 7621192
TI  - Variations in the electrocardiograms of young adults: are revised criteria for
      thrombolysis needed?
AB  - OBJECTIVE: The evaluation of chest pain in young adults has changed with the
      recognition of cocaine-induced myocardial ischemia. The high frequency of
      abnormal electrocardiograms (56-84%) in the cocaine-user population is largely
      due to "normal" electrocardiographic variants (early repolarization). The authors
      sought to determine the frequency of these "normal" variants in a young
      population, and whether these findings can be confused with acute ischemia.
      METHODS: A prospective convenience sample of subjects aged 18 to 35 without known
      heart disease was interviewed and had 12-lead electrocardiographic tracings
      performed. An emergency physician (physician 1) and a cardiologist (physician 2)
      read the tracings while blinded to patient history, age, and race. When the
      physicians disagreed, another physician adjudicated the diagnosis. RESULTS: Four
      hundred fourteen subjects (127 black, 175 Hispanic, and 112 Caucasian) were
      enrolled. Overall, 154 tracings (37%) were normal, 245 (59%) were abnormal but
      nondiagnostic for ischemia, and 15 (4%) were consistent with ischemia.
      Frequencies of repolarization "abnormalities" as determined by physicians 1 and
      2, respectively, were: blacks, 32%, 51%; Hispanics, 26%, 35%; Caucasians, 17%,
      27%; chi-squared, p = 0.02 and 0.0004. Patients with ischemic electrocardiograms
      according to physician 1 had a high frequency of repolarization "abnormalities"
      according to physician 2, and vice versa (100%, 61%). Electrocardiographic
      criteria for thrombolytic use per physician 2 were present in 31 patients (7%):
      blacks, 9%; Hispanics, 10%; and Caucasians, 2%; chi-squared, p = 0.03.

PMID- 7621193
TI  - Public health, health care reform, and emergency medicine.

PMID- 7621194
TI  - Public health, injury control, and emergency medicine.

PMID- 7621195
TI  - Triage of nonurgent patients out of the emergency department.

PMID- 7621198
TI  - That special relationship--SAEM/EMRS.

PMID- 7621196
TI  - Statewide trauma systems: the bottom line.

PMID- 7621197
TI  - Publication bias.

PMID- 7621199
TI  - Failure to validate a predictive model for refusal of care to emergency
      department patients.
AB  - OBJECTIVE: To determine whether previously developed triage criteria for refusal
      of care to patients presenting to an emergency department (ED) with nonurgent
      problems could be validated for an independent patient population. METHODS: A
      convenience sample of 534 adults presenting to a municipal hospital ED between
      July 1, 1992, and October 15, 1992, who met preestablished criteria for refusal
      of care were entered into a prospective, observational, cohort study. The single
      target outcome variable was hospitalization. In order to optimize the criteria's
      performance, both the triage nurse and the physician caring for the patient had
      to agree that all criteria for "refusal of care" were specifically met. No
      patient was refused care, nor was a patient's management or disposition
      interfered with in any way by the investigators. All patients were followed until
      hospital admission or release from the ED. RESULTS: Six (1.1%) of 534 patients
      (95% CI 0.4-2.4) who met the criteria for refusal of care were hospitalized. This
      represents a greater than 50-fold difference in incidence of hospitalization when
      compared with that found by other investigators, who reported that only 0.02%
      (95% CI 0.0004-0.04) of those patients who were refused care subsequently
      required hospitalization (p < 10 (-7)). CONCLUSION: The authors were unable to
      validate a previously developed predictive model for refusal of care to patients
      presenting to an ED. Refusal of care to selected ED patients based on current
      guidelines is not a viable solution to overcrowding. Alternative strategies must
      be sought.

PMID- 7621200
TI  - Oregon trauma system: change in initial admission site and post- admission
      transfer of injured patients.
AB  - OBJECTIVE: Associate statewide trauma system development with a change in the
      percentage of injured patients initially hospitalized at Levels I and II
      categorized trauma hospitals and a change in the length of stay (LOS) prior to
      arrival at a Level I or II hospital (PRE-LOS) and total LOS (T-LOS) for post
      admission transfer patients. METHODS: A retrospective analysis was performed
      using a hospital discharge database of 235,395 discharges with codes for acute
      injury managed at 74 acute care hospitals in Oregon State from 1983 to 1991.
      Primary outcome measures were admission site and transfer patient PRE-LOS and T
      LOS. Predicator variables included category of initial hospital admission site,
      injury severity scale (ISS) score, head injury, age, and status of trauma system
      (pre-system, 1983 to 1987; transitional, 1988 to 1989; and post-system, 1991 to
      1992). RESULTS: There was a significant increase in the percentage of initial
      admissions to hospitals with Level I and II categorization (17.6%, 26.2%, and
      27.6% for the three periods of development, respectively; p < 0.00001). The
      percentage of patients with ISS scores greater than 15 admitted initially to
      Level I or II hospitals increased from 33.4% to 52.6% and 57.3%; p < 0.00001).
      Only 1,059 0.57%) of 185,321 patients initially admitted to Level III, Level IV,
      or noncategorized hospitals were transferred to a Level I or II hospital. Mean
      PRE-LOS for 1.059 transferred patients showed a significant decrease with system
      development (2.3, 1.9, and 1.8 days, respectively; p < 0.02). When adjusted for
      age, ISS score, and head injury effects, mean T-LOS was significantly reduced for
      the transitional and post-system periods (p < 0.05). CONCLUSIONS: In Oregon,
      development of a statewide trauma system was associated with increased initial
      admissions to Level I and II trauma hospitals. For those patients transferred to
      higher levels of care post- admission, hospital LOSs were decreased with trauma
      system development.

PMID- 7621201
TI  - Identification of ethanol-intoxicated patients with minor head trauma requiring
      computed tomography scans.
AB  - OBJECTIVE: To determine whether clinical parameters and neurologic scores can be
      used to guide the decision to obtain computed tomography (CT) head scans for
      ethanol- intoxicated patients with presumed-minor head injuries. METHODS: In a
      prospective cohort analysis, 107 consecutive adult patients who presented to a
      county emergency department (ED) with serum ethanol levels >80 mg/dL and minor
      head trauma were studied. Commonly used clinical variables were determined for
      each patient. Each patient also underwent an abbreviated neurologic scoring
      examination and a Glasgow coma scale (GCS) score evaluation at the time of
      presentation and one hour later, after which a cranial CT scan was done. For
      purposes of analysis, patients with and patients without intracerebral injuries
      visible on CT scans of the head were compared. RESULTS: Nine of 107 patients
      (8.4%; 95% confidence interval [CI] = 3.9-15.4%) had CT scans that were positive
      for intracerebral injury. Two patients (1.9%; 95% CI = 0.2-6.6%) needed
      craniotomy. Five patients had hemotympanum and two patients had bilateral
      periorbital ecchymosis, but CT scans were negative for intracerebral injury in
      these patients. There was no statistically significant difference between the
      patients with and without CT scan abnormalities, based on the clinical variables,
      the GCS scores, or the abbreviated neurologic scoring examinations at
      presentation or at one hour. CONCLUSION: The prevalence of intracerebral injury
      in CT scans of ethanol-intoxicated patients with minor head injuries was 8.4%.
      Commonly used clinical parameters and neurologic scores at presentation and one
      hour later were unable to predict which patients would have intracerebral
      injuries and evidenced by CT scans. Our low (1.9%) neurosurgical intervention
      rate supports the need to develop a selective approach to CT scanning in this
      population.

PMID- 7621202
TI  - Comparison of sinus x-rays with computed tomography scans in acute sinusitis.
AB  - OBJECTIVE: To determine the sensitivity and specificity of sinus x-rays of
      patients clinically diagnosed as having acute sinusitis. METHODS: Thirty
      consecutive adult, nonpregnant emergency department (ED) patients clinically
      diagnosed as having acute sinusitis and meeting study criteria were entered into
      the study. Sinus x-rays were obtained immediately after study entry and sinus
      computed tomography (CT) scans were done within 72 hours. Radiologic criteria for
      sinusitis were defined as more than 3 mm of mucoperiosteal thickening (MPT), an
      air/fluid (A/F) level, or opacification. All films were read in a blinded fashion
      [CT scans by two radiologists and plain film by two emergency medicine (EM) staff
      members and the same radiologists]. A third radiologist 'interpreted Ct scans
      when the initial radiologists disagreed. RESULTS: Sinus CT scans were obtained
      for 29 of 30 patients. Radiologists interpreted 28 of 29 CT scans identically,
      with 21 being positive for sinusitis. Sensitivity and specificity of x-rays were
      57% and 88%, 62% and 88%, 67% and 75%, and 48% and 100% for the two radiologists
      and the two EM physicians, respectively. Four ethmoid, five frontal, and five
      sphenoid sinuses were opacified or had A/F levels on CT scan. No ethmoid,
      frontal, or sphenoid sinus was interpreted as being opacified or having an A/F
      level on plain film. Sensitivity and specificity of maxillary sinus opacification
      or A/F level on x-ray were 70% and 100%, and 70% and 100%, and 70% and 96%, and
      70% and 96% for the two radiologists and the two EM physicians, respectively.
      Mean concordances (kappa) of x-ray and CT scan interpretations for the four
      reviewers were 0.34 (range, 0.30-0.39) for the diagnosis of sinusitis and 0.77
      (range, 0.74-0.79) for maxillary sinus opacification or A/F level. CONCLUSIONS:
      Sinus x-rays are less sensitive than sinus CT scans for demonstration of
      radiographic changes consistent with acute sinusitis. Sinus plain films may not
      be reliable enough to assist with clinical decision making. If severity of
      patient illness requires diagnostic certainty, more sensitive imaging studies,
      such as CT scans of the sinuses, should be considered.

PMID- 7621203
TI  - Stress levels in EMS personnel: a longitudinal study with work-schedule
      modification.
AB  - OBJECTIVE: To determine if stress levels of emergency medical services (EMS)
      personnel can be reduced by adjusting work schedules to personnel preferences.
      METHODS: A prospective, longitudinal, cohort study with a work-schedule
      modification intervention was performed. All EMS personnel employed by the City
      of Cleveland EMS were eligible for participation. EMS employees voluntarily
      completed an abbreviated medical personnel stress survey (MPSS-R), a 20- question
      validated stress-assessment tool, in September 1989, February 1991, and September
      1991. A new scheduling pattern was introduced March 1991. At that time, 27 EMS
      employees volunteered to work the new schedule (12 hours/ shift: 3 days on/2 days
      off/2 days on/3 days off). The remaining 109 EMS employees remained on the old
      schedule (8 hours/shift: 6 days on/2 days off). RESULTS: Mean MPSS-R stress
      scores increased significantly from September 1990 (61.9 +/- 7.87) to September
      1991 (65.08 +/- 7.23) (p < 0.05). In September 1991, mean stress scores of EMS
      personnel working the new schedule (64.39 +/- 7.82) were not significantly lower
      than stress scores of EMS personnel working the old schedule (65.25 +/- 7.10).
      CONCLUSION: Stress in EMS personnel increased despite a new schedule pattern
      designed to accommodate the preferences of EMS personnel.

PMID- 7621204
TI  - Social-work services in an emergency department: an integral part of the health
      care safety net.
AB  - OBJECTIVE: To quantify and describe the activities of social workers dedicated to
      a large urban emergency department (ED). METHODS: A retrospective case series of
      all patients seen by social workers in an urban university hospital ED over a
      period of six weeks. RESULTS: Social- work service was provided to 5% of ED
      patients. Three distinct groups of patients were usually seen by social workers:
      the elderly, young adults, and children less than 5 years of age. The median age
      of the group referred for social work services was greater than that of the ED
      population as a whole; triage acuity also was greater in the referred group. The
      types of services provided varied with age. Among those patients with social-work
      consultations, the average time spent with each patient was over one hour and did
      not vary according to the age, sex, race, or insurance status of the patient.
      More than 60% of the social worker's time was spent with patients or their
      significant others. CONCLUSION: Social workers provide valuable services to ED
      patients. The availability of social workers in the ED reduces the demands for
      emergency physicians and nurses to arrange home health care, nursing home
      placement, and other social-service functions. Cost savings through diversion of
      nonacute social admissions are possible. The types of services provided vary and
      depend to a large extent on patient age. The availability of dedicated social
      work personnel in the ED and the education of emergency personnel regarding the
      services that they can provide should be beneficial for patients, staff, and the
      hospital served.

PMID- 7621205
TI  - Judicial outcome for the intoxicated driver admitted to a regional trauma center.
AB  - OBJECTIVE: To examine the judicial outcomes for intoxicated drivers who were
      admitted to regional trauma centers as a result of motor vehicle collisions
      (MVCs). METHODS: A retrospective review of the trauma registry of a Level I
      trauma center was conducted for the period from January 1, 1989, through December
      31, 1990. Inclusion criteria for entry into the study were 1) identification of
      the patient as the driver involved in an MVC, 2) a blood alcohol content (BAC)
      above 0.10 g/dL, and 3) survival until discharge from the hospital. A total 245
      patients from the trauma registry met the inclusion criteria. The number of
      persons from the submitted list who were later convicted of driving under the
      influence of alcohol (DUI) was obtained from the Department of Motor Vehicles
      (DMV) of the Common- wealth of Virginia. RESULTS: Of the list submitted to the
      DMV, only nine individuals (3.7%; 95% confidence interval = 1.3--6.0%) were
      convicted of DUI during the MVCs that led to hospitalization during the study
      period. During the same time period, the statewide conviction rate for DUI-cited
      drivers was 85%. CONCLUSION: Admission to the trauma service at a Level I trauma
      center may provide a refuge from legal consequences for intoxicated drivers
      involved in MVCs.

PMID- 7621206
TI  - A prospective evaluation of risk factors for infections from dog-bite wounds.
AB  - OBJECTIVE: To define risk factors for infections from dog- bite wounds and to
      model the probability of wound infection in patients presenting without infection
      who are treated as outpatients. METHODS: A prospective survey of 769 consecutive
      dog-bite victims presenting over a two-year period to a community hospital
      emergency department (ED) with an emergency medicine residency program. A
      standardized wound-cleaning protocol was used, which included debridement and
      wound closure when indicated. Wounds were examined for infection at follow-up.
      Variables analyzed included demographic data (patient age, gender, race); wound
      information (wound age, type, number, location, depth); and treatment (prior to
      hospital, ED debridement, suturing, tetanus or rabies shots, antibiotics).
      RESULTS: There were 734 patients with complete records. These patients had a mean
      age of 13.4 +/- 13.2 years (range, 4 months to 71 years). Infection was evident
      in 2.5% of the wounds upon presentation. There were 704 patients (765 wounds)
      managed as outpatients and without wound infection upon presentation. Wounds were
      distributed as follows: 26.7% head/neck, 20.4% hand, 15.7% arm, 10.1% trunk, 9.5%
      thigh, 15.9% leg, and 1.7% foot. There were 32.9% puncture, 39.9% full-thickness,
      and 60.1% partial-thickness wounds. Wound infections were diagnosed in 2.1% Of
      these wounds at follow-up. Wounds requiring surgical debridement had a sevenfold
      higher infection rate (p = 0.01). Patients more than 50 years of age had a
      sixfold higher infection rate than younger patients (p = 0.05). Stepwise logistic
      regression found the following variables to be the best predictors for wound
      infection: full-thickness [p = 0.006, odds ratio (OR) = 6.23], female gender (p =
      0.048, OR = 2.88), and wound debridement (p = 0.024, OR = 5.01). Combinations of
      these three variables predict infection rates from 0.35% to 23.9%. CONCLUSION: A
      low wound infection rate was seen in this cohort of dog-bite victims who were
      treated on an outpatient basis. Wound depth, patient gender, and wound
      debridement were the clinical variables that best predicted the likelihood of
      developing infection. Future interventional studies should concentrate on wounds
      with high probabilities of infection.

PMID- 7621208
TI  - Closed reduction of a traumatically dislocated testicle.
AB  - Traumatic testicular dislocation is an uncommon event, with fewer than 60 cases
      having been reported in literature. It is imperative that the emergency physician
      be aware of the possibility of testicular dislocations following perineal trauma
      and either seek emergent urologic consultation or attempt relocation of the
      testicle immediately. Testicular dislocation (following a motorcycle crash) that
      was successfully managed by closed reduction in the emergency department (ED) is
      presented. Following a benign course during subsequent observation, the patient
      was released with close urologic follow-up.

PMID- 7621209
TI  - Clinical pearls: index finger pain blisters.

PMID- 7621207
TI  - Positive-outcome bias: comparison of emergency medicine and general medicine
      literatures.
AB  - OBJECTIVE: The existence of positive-outcome bias in the medical literature is
      well established. Positive-outcome bias in two emergency medicine journals was
      compared with that found in two general medicine journals. METHODS: Published
      original contributions from Annals of Emergency Medicine, American Journal of
      Emergency Medicine, JAMA, and New England Journal of Medicine were reviewed.
      Articles were categorized as demonstrating a positive or negative outcome or
      showing no difference using new criteria. Descriptive articles were excluded.
      RESULTS: Of 700 articles reviewed, 177 emergency medicine and 211 general
      medicine articles met the study criteria. The emergency medicine journals had 142
      articles (80%) with positive outcomes, 27 (15%) with negative outcomes, and 8
      (5%) with no difference. The general medicine journals had 169 articles (80%)
      with positive outcomes, 33 (16%) with negative outcomes, and 9 (4%) with no
      difference. There was no significant difference between journal groups (chi
      square; p = 0.99). The power of the study was 0.80 to detect a difference of 15%
      between groups with alpha set at 0.05. CONCLUSION: There was no significant
      difference in the proportions of positive-outcome studies published in this
      sample of the emergency medicine literature compared with the general medicine
      literature. The potential impact of positive-outcome bias and methods of dealing
      with the problem are reviewed.

PMID- 7621211
TI  - Managed health care and emergency medical services.

PMID- 7621210
TI  - A public health approach to emergency medicine: preparing for the twenty-first
      century.
AB  - This paper focuses on the implications of an inadequate public health/preventive
      health care system for emergency medicine (EM), the role that EM providers can
      play in remedying critical health problems, and the benefits gained from a public
      health approach to EM. A broad definition of public health is adopted, suggesting
      shared goals of public health and EM. Critical problems posed for EM include
      alcohol, tobacco, and other drug abuse; injury; violence; sexually transmitted
      diseases and human immunodeficiency virus (HIV) infection occupational and
      environmental exposures; and the unmet health needs of minorities and women. A
      blueprint for future merging of public health issues with EM is presented that
      includes the application of public health principles to 1) clinical practice; 2)
      public education, community involvement, and public policy advocacy; 3)
      development of medical school and residency public health/prevention curricula
      and teaching methods; and 4) research opportunities and surveillance. Finally,
      recommendations are proposed that require restructuring the present health care
      system to provide resources, incentives, and organizational changes that promote
      an integration of public health and preventive services in the practice of EM.

PMID- 7621212
TI  - E-codes assigned from emergency-department records: is the information there?

PMID- 7621213
TI  - Volunteer emergency medicine faculty.

PMID- 7621214
TI  - Does topical lidocaine attenuate the pain of infiltration of buffered lidocaine?
AB  - OBJECTIVE: To determine whether topical lidocaine attenuates the pain of buffered
      lidocaine infiltration. METHODS: This was a prospective, randomized, double
      blind, placebo-controlled trial conducted at a university-based ED. The subjects
      were adults who had lacerations being repaired using local anesthesia. Two 0.5-mL
      injections of buffered lidocaine were given in a standardized manner. The first
      was given prior to application of topical study solution. The second was given on
      the opposite side of the laceration after topical application of study solution,
      which was 5 mL of either 2% lidocaine or saline placebo. The pain of each
      infiltration was measured using a visual analog pain scale. Pain scores were
      calculated and compared using a Wilcoxon test with significance defined as p < or
      = 0.05. RESULTS: A total of 54 subjects participated; 29 received lidocaine
      topically and 25 received placebo. The groups were similar with respect to age,
      gender, wound length, wound location, and initial pain score. Pain scores
      decreased by 11.6 +/- 18.6 mm for lidocaine and 10.9 +/- 20.9 mm for placebo (p >
      0.5). The study had the power to detect a 15-mm pain score difference (alpha =
      0.05 and beta = 0.20) on a 100-mm scale. CONCLUSION: Topical 2% lidocaine does
      not attenuate the pain of infiltration of buffered lidocaine more than does
      topical normal saline. Investigation of other topical anesthetics with and
      without epinephrine in conjunction with buffered lidocaine is warranted.

PMID- 7621215
TI  - Weapon carriage among major trauma victims in the emergency department.
AB  - OBJECTIVE: To determine the occurrence of weapon carriage by major trauma
      patients at a university/county hospital ED. METHODS: Retrospective observational
      study of major trauma patients seen in the ED of a major urban trauma center in
      Los Angeles from 1979 to 1993. All major trauma patients were searched routinely
      for weapons by the security police. Cases of violence in the ED caused by these
      weapons were reviewed. RESULTS: Over the 14-year period, 26.7% of the victims of
      major trauma presenting to ED were armed with lethal weapons. The occurrence of
      automatic weapon seizure increased significantly from an annual rate of only 0.2
      in the first five years to an average of 17 over the last five years (p < 0.001).
      A total of 115 "incidents" of violence involving weapons in the ED were recorded
      during this period; 1.7% of the weapons brought to the ED led to violence and
      injury. There were four fatalities of armed and dangerous patients, but only six
      minor injuries to the staff. No other (unarmed) patient in the ED at the time of
      these incidents was injured. CONCLUSION: ED major trauma patients at one urban
      trauma center in Los Angeles frequently carry weapons, including automatic
      military weapons. In addition to violence prevention measures such as weapon
      confiscation, plans must be made and practiced for the management of violence
      within the "sacrosanct" hospital doors to protect both patients and ED personnel.

PMID- 7621216
TI  - Effect of gender on the emergency department evaluation of patients with chest
      pain.
AB  - OBJECTIVE: To assess chest pain evaluation as reflected in the documentation of
      the evaluation process for women vs men in one emergency department (ED).
      METHODS: In this retrospective case series, patient charts were reviewed for
      documentation in accordance with a clinical policy for chest pain evaluation.
      Patient demographics and the frequencies of inclusion of the following items were
      determined: five descriptors of chest pain, associated symptoms, risk factors for
      coronary artery disease, receipt of physical examination, and receipt of ECG.
      RESULTS: Over a three-month period, 132 men and 150 women were evaluated for
      chest pain and entered in the study. There was no significant difference in age
      between men and women overall, but in the subgroup of patients who were admitted
      to the hospital, the women were significantly older than the men by an average of
      five years (p = 0.04). Fifty-five percent of all the patients were admitted to
      the hospital. The men were admitted to the hospital significantly more often than
      were the women (p = 0.01), with a relative risk of admission for women vs men
      0.76 (95% CI = 0.62-0.94). There was no significant difference between the men
      and the women for any of the process of evaluation items in the overall group or
      in the hospital-admission and release-home subgroups. CONCLUSION: The authors'
      findings do not support the existence of a gender difference in ED chest pain
      evaluations, as reflected by documentation of the evaluation process. However,
      men were more likely to be admitted to the hospital for evaluation of coronary
      artery disease than were women.

PMID- 7621217
TI  - Emergency department presentation of patients with conversion disorder.
AB  - OBJECTIVE: To describe the presenting symptoms and other features of ED patients
      diagnosed as having conversion disorder. METHODS: A retrospective chart review
      was carried out on the records of ED patients who had had final ED or in-hospital
      diagnoses of conversion disorder. Cases from 1982 to 1992 at a 566-bed rural
      tertiary care hospital with a residency program in emergency medicine were
      reviewed for patient age and gender, presenting signs and symptoms, ED diagnostic
      evaluation, disposition, and comorbidity. RESULTS: Of 42 patients who had
      conversion disorder diagnoses, 24 were women and 18 were men. Twenty-one (50%) of
      the patients were diagnosed in the ED, and of those patients, ten were released
      home from the ED. Patient age ranged from 5 to 70 years, with a mean age of 33
      years for women and 34 years for men. Most clinical symptoms mimicked neurologic
      disorder (weakness, pain, seizure-like activity, loss of consciousness, etc).
      Thirty patients (71%) received laboratory studies in the ED and two others
      received laboratory studies on admission. Seventeen (40%) patients had computed
      tomography of the head and five (12%) patients had magnetic resonance imaging of
      the head. Twelve (29%) patients had previous histories of psychiatric disorders,
      four (10%) had histories of alcohol and drug abuse, two (5%) had prior conversion
      reactions, three (7%) had chronic illnesses, and four (10%) had been victims of
      previous head trauma. CONCLUSION: Patients with conversion disorder in the ED
      usually present with neurologic symptoms and undergo multiple diagnostic tests.
      Comorbidity is common. Early psychiatric evaluation may assist in the diagnosis
      and evaluation of patients with suspected conversion disorder in the ED.

PMID- 7621218
TI  - Resident service hours in emergency medicine. SAEM Education Committee.
AB  - OBJECTIVE: The number of hours worked by residents in all specialties has become
      a controversial issue. Residents often are expected to competently conduct
      patient care activities and to take educational advantage of clinical experiences
      in spite of frequent fatigue and sleep deprivation. This survey of residency
      directors was designed to assess the scheduled clinical time for emergency
      medicine (EM) residents. METHODS: A 13-question survey dealing with time
      commitments of EM residents was sent to the residency directors of all accredited
      EM residency programs in the United States in the fall of 1991. Residency
      directors were asked to indicate the number of shifts, hours, and days off per
      week; and the number of night shifts and weekend days off per month for each
      postgraduate year of residency training (PGY1-PGY4). Directors also were asked
      whether shifts were scheduled randomly or predictably with progression from days
      to nights with time off after nights. RESULTS: Seventy of 71 (98.6% response
      rate) residency directors responded. Residents were scheduled for an average of
      49.1 hours per week. Scheduled hours decreased from an average of 51.9 at the
      PGY1 level to an average of 44.5 at the PGY4 level. A similar progression with
      year of training was noted for scheduled night shifts/month, days off/week, and
      weekend days off/month. A PGY1 trainee averaged 7.0 night shifts/month, 1.9 days
      off/week, and 3.0 weekend days off/month; while a PGY4 trainee averaged 5.3, 2.4,
      and 3.2, respectively. Only 40% of the directors reported predictable scheduling
      progressing from days to nights. CONCLUSION: Emergency medicine resident
      schedules, as reported by residency directors, fall well within current specialty
      specific requirements and compare favorably with the reported numbers for other
      specialties. However, because large ranges in scheduling parameters were
      reported, the data may be of value to residency directors, residents, and
      prospective residents. Most programs did not report a predictable schedule
      progression of shifts.

PMID- 7621219
TI  - Successful treatment of amoxapine-induced refractory status epilepticus with
      propofol (diprivan)
AB  - Tonic-clonic seizure activity is a recognized complication of amoxapine overdose.
      Refractory drug-induced status epilepticus is associated with significant
      morbidity and mortality. Standard regimens for controlling status epilepticus may
      be ineffective for aborting drug-induced seizures. The authors report the case of
      a 30-year-old woman who presented with an amoxapine overdose that deteriorated
      into status epilepticus refractory to conventional therapy. Propofol given by
      intravenous bolus and maintenance infusion successfully halted the patient's
      seizure activity. This case suggests that propofol may be effective as an
      anticonvulsant in refractory drug-induced status epilepticus.

PMID- 7621221
TI  - Turning quality-related activities into quality research.

PMID- 7621220
TI  - Abdominal wall hematoma in an elderly man.
AB  - This report describes an abdominal wall hematoma that occurred in an unusual
      location and resulted in significant hemorrhage in a generally healthy
      individual. Angiography-directed therapeutic embolization was halted due to an
      embolic complication. Evidence of continued hemorrhage led to surgical
      intervention. After a right flank incision was made, fresh blood as well as
      approximately 1 L of clotted blood were evacuated from the abdominal wall. After
      resection of a portion of the twelfth rib, the twelfth intercostal artery was
      noted to be actively bleeding and was ligated. This operative procedure
      controlled the patient's blood loss. The etiologies, presenting findings,
      diagnostic studies, and modes of therapy reported for abdominal wall hematomas
      are reviewed.

PMID- 7621222
TI  - Ophthalmologic procedures in the emergency department--Part II: Routine
      evaluation procedures.
AB  - The emergency physician (EP) must be familiar with performance of ophthalmologic
      procedures for evaluation and treatment of a multitude of eye complaints. This
      article is the second of three articles addressing ophthalmologic procedures
      potentially of use by the EP. This article reviews the indications and the
      techniques for the following routine procedures: visual acuity testing, pupil
      dilatation, topical anesthesia use, and tonometry. Criteria for consultation also
      are addressed.

PMID- 7621223
TI  - Violence and general security in the emergency department.
AB  - OBJECTIVE: To describe cases of violence related to weapons in a university
      hospital and urban county ED and to provide related recommendations for ED staff
      security. METHODS: Descriptive analysis and case examples of weapons-related
      assaults in one urban ED for the period 1979-1993. RESULTS: Over a 14-year
      period, 115 "incidents" of weapons-related violence were identified during the
      management of approximately 980,000 patients. Examples of ED violence are
      described. CONCLUSION: Emergency department staff should prepare for the
      possibility of violence by 1) recognizing the danger, 2) rehearsing response
      mechanisms, and 3) debriefing after incidents. In particular, plans must be made
      and practiced for the time when external violence follows the surviving victims
      of gang activity through the "sacrosanct" hospital doors. Protection of patients
      and ED personnel must be ensured. In many urban settings, appropriately armed
      security guards must be immediately accessible to the ED staff. Other suggestions
      for ED protection are given.

PMID- 7621224
TI  - Impact of an EM club on senior student elective enrollment.

PMID- 7621225
TI  - Clarification of related publications.

PMID- 7621226
TI  - Computerized literature search in the ED: patient care impact.

PMID- 7621227
TI  - Acidosis in acute hemorrhage: detrimental or elemental?

PMID- 7621228
TI  - Into the looking glass.

PMID- 7621229
TI  - Gender and chest pain evaluation.

PMID- 7621230
TI  - Clinical skill assessment: can we do better?

PMID- 7621231
TI  - Multiple resuscitation regimens in a near-fatal porcine aortic injury hemorrhage
      model.
AB  - OBJECTIVE: To compare early and delayed blood administrations in animals
      subjected to near-fatal hemorrhage in the presence of a vascular injury and
      resuscitated to different mean arterial pressures (MAPs). METHODS: Fifty-four
      immature swine with 4-mm infrarenal aortic tears were bled to a pulse pressure of
      5 torr and then resuscitated (estimated blood loss 40 to 45 mL/kg). Groups I, II,
      and III were resuscitated with shed blood at a rate of 2 mL/kg/min, followed by
      normal saline at a rate of 6 mL/kg/min. Groups IV, V, and VI received the same
      fluids in reverse order. The fluids were infused intermittently to maintain MAPs
      of 40, 60, and 80 torr. The animals were observed for 60 minutes or until death.
      RESULTS: The animals resuscitated to a MAP of 80 torr experienced significantly
      higher intraperitoneal hemorrhage volumes and mortality than did the animals
      intentionally maintained hypotensive, regardless of whether blood or normal
      saline was administered first. There was no significant difference in mortality
      or hemorrhage volumes between any of the groups intentionally maintained
      hypotensive. The animals maintained at a MAP of 60 torr were significantly less
      acidotic than were the animals resuscitated with the same fluid regimen but to a
      MAP of 40 torr. Early blood administration also minimized the acidosis associated
      with hypotensive resuscitation. CONCLUSION: In this model of near-fatal
      hemorrhage with a vascular injury, maintenance of the hypotensive state produced
      comparable improvements in one-hour survival and reductions in hemorrhage volume
      regardless of whether blood or saline was administered first. Although
      hypotensive resuscitation resulted in improved outcome, it was associated with
      significant acidosis. This effect was minimized with moderate rather than severe
      underresuscitation and early blood administration.

PMID- 7621232
TI  - The quantity of cause-of-injury information documented on the medical record: an
      appeal for injury prevention.
AB  - OBJECTIVE: To determine how much information about the cause of injury (available
      at the time of ED treatment) is documented on the medical record. This
      information is used by medical records coders to assign e-codes. METHODS:
      Quantitative "stages of information" were defined: stage 1 = the maximum amount
      of information available from the patient, as collected by a trained research
      assistant; stage 2 = the amount of information obtained by the care provider
      during the patient interview; and stage 3 = the amount of information the care
      provider documented in the medical record. Comparisons were made between the
      three stages; subgroup analyses compared amounts of information loss between the
      stages for levels of care provider and cause-of-injury information categories.
      RESULTS: Information was obtained from 109 patients. Only 46% of the cause-of
      injury information available during the ED visit was recorded on the medical
      record. Incomplete history taking (obtaining 68% of the available information)
      and failure to document (writing 67% of the information obtained during the
      patient interview) contributed equally to the loss of information. The most
      information was obtained about who had received the injury (72%) and the least
      amount of information was in the category of where the injury had occurred (14%).
      Attending physicians collected the most information (74%) but documented
      significantly less (65%) than did physician assistants (70%) or medical students
      (81%). Medical students collected the least (65%) but documented the most,
      resulting in the students' medical records' being the most complete (52%) for
      cause-of-injury information. CONCLUSION: Emergency providers obtain significantly
      less cause-of-injury information than is available from the patient. Also, these
      providers' handwritten medical records contain significantly less cause-of-injury
      information than was obtained during the patient interview.

PMID- 7621233
TI  - Butyrate-inducible and tumor-restricted gene expression by adenovirus vectors.
AB  - Efficient introduction of biologically active genes into tumor cells in vivo
      would facilitate cancer gene therapy. In this study, recombinant adenoviruses
      mediated high-level expression of reporter genes in both human and murine tumor
      cell lines and freshly resected human solid tumors in vitro. When adenovirus
      vectors were inoculated intratumorally in a living animal, reporter activity was
      detected only in the tumor nodule and not in other sites, in contrast to
      intracardiac injections in which expression was found in several organs.
      Adenovirus-mediated gene expression was further enhanced by butyrate treatment.

PMID- 7621235
TI  - Long-term protection of recipient mice from lethal doses of methotrexate by
      marrow infected with a double-copy vector retrovirus containing a mutant
      dihydrofolate reductase.
AB  - A double-copy Moloney murine leukemia virus-based retroviral construct containing
      both the NEOr gene and a mutated dihydrofolate reductase cDNA (Leu 22-->Arg) was
      used to infect mouse bone marrow cells. The infected mouse marrow was returned to
      lethally irradiated mice. Primary, secondary, and even tertiary recipients
      transplanted with bone marrow cells infected with the recombinant virus showed
      protection from lethal methotrexate toxicity. The viral construct containing a SV
      40 promoter in the U3 region of the 3' long terminal repeat appeared to be more
      effective than a similar construct containing the adenosine deaminase promoter,
      although both afforded protection. Evidence for integration into blood cells of
      both the NEOr gene and the mutated dihydrofolate reductase gene was obtained by
      polymerase chain reaction; sequencing of the amplified dihydrofolate reductase
      cDNA showed the presence of the point mutation. These results indicate that early
      hematopoietic progenitor cells in the mouse can be successfully transduced with a
      drug resistance gene.

PMID- 7621234
TI  - Serial transplantation shows that early hematopoietic precursor cells are
      transduced by MDR-1 retroviral vector in a mouse gene therapy model.
AB  - The administration of high and repeated doses of chemotherapy has been hampered
      by the bone marrow toxicity imposed by these drugs. This obstacle can be
      circumvented by the introduction of chemotherapy resistance genes into the normal
      marrow cells, which are then transplanted back into the patient. To show that
      this approach can improve our ability to safely deliver high doses of
      chemotherapy, we used an animal model system to transplant bone marrow cells
      which have been transduced with a safety-modified retrovirus containing human
      multiple-drug resistance (MDR-1) cDNA into lethally irradiated mice. These
      studies produced mice whose bone marrow and peripheral blood displayed an
      increased level of MDR-1 expression and resistance to the myelotoxic side effects
      of Taxol. To determine whether sufficient numbers of early hematopoietic
      precursor cells were transduced with the MDR-1 retrovirus so that durable Taxol
      resistant hematopoiesis would result, we serially transplanted the modified bone
      marrow cells into each of six successive cohorts of BALB/c mice. Taxol-resistant
      hematopoiesis with little or no myelosuppression was observed in all six of the
      cohorts. These data suggest that very early precursor cells were transduced by
      the vector. This animal model may be of use in the development of genetic therapy
      programs which use bone marrow to introduce therapeutic molecules into the
      systemic circulation, since it permits in vivo selection of genetically modified
      hematopoietic progenitor cells. Furthermore, the retroviral vector system we have
      used could have an immediate impact in the clinical setting, where it can protect
      patients from the myelosuppressive side effects of Taxol in advanced stages of
      human epithelial cancers.

PMID- 7621236
TI  - Local IL-4 delivery enhances immune reactivity to murine tumors: gene therapy in
      combination with IL-2.
AB  - Tumor cells transduced with the IL-4 gene demonstrate reduction of growth
      associated with macrophage and eosinophilic infiltrates, generation of cytotoxic
      T-cells, and protective immunity. Using murine IL-4 retroviral vectors, murine
      fibroblasts and tumors that produce from 50 to 5000 U of IL-4/10(6) cells per 24
      hours as determined by ELISA and bioassay were successfully transduced. In
      blinded studies using C57BL/6 and BALB/c mice, we have shown that tumor growth
      can be inhibited (mean delay of 10 days compared with controls; P < .05) and in
      some cases, completely suppressed by the coinjection of viable tumor with IL-4
      producing fibroblasts (tumor free > 100 days; P < .001). Animals that are able to
      reject an initial tumor inoculate can also completely reject subsequent parental
      tumor challenge of 10(5) cells (P < .001) while challenge of 10(6) parental tumor
      cells results in a significant delay of tumor induction (P < .05). In addition,
      immunization with IL-4 transduced fibroblasts and irradiated tumor cells resulted
      in complete suppression of parental tumor challenge in animals that received the
      high-dose IL-4 delivery. Finally coadministration of systemic IL-2 led to
      enhancement of IL-4 gene therapy resulting in a 20-day delay of preestablished
      tumor growth compared with controls (P < .05).

PMID- 7621237
TI  - Vaccination with IL-2-secreting tumor cells stimulates the generation of IL-2
      responsive T cells and prevents the development of unresponsiveness.
AB  - Infection of CMS5 tumor cells with retroviral constructs containing interleukin-2
      (IL-2) cDNA and selection in medium supplemented with G418 resulted in the
      isolation of clones which secreted IL-2. Whereas injection of parental tumor
      cells resulted in progressive tumor growth, tumor cells secreting high levels of
      IL-2 were rejected. Furthermore, in animals vaccinated with IL-2-secreting cells,
      the immunosuppression associated with the inoculation of parental tumor cells did
      not develop, and these animals resisted a challenge with viable tumor cells. To
      better understand the functional differences in the anti-tumor responses of
      immune and tumor-bearing mice which are at the basis for these diverse responses,
      we used an in vitro model to analyze interactions between splenic lymphocytes and
      tumor cells. Spleen cells isolated from either tumor-bearing or immune mice
      proliferated vigorously when cultured alone for 6 days, but much less in the
      presence of parental tumor cells. This effect could not be transferred with
      supernatant from tumor cell lines. Spleen cells from tumor-bearing mice remained
      unresponsive, while those from immune mice proliferated well in response to IL-2
      secreting tumor cells. Only spleen cells from immune animals were able to develop
      cytotoxicity against CMS5 cells following in vitro restimulation. These results
      are consistent with the interpretation that exposure to parental tumor cells
      inhibited cell-mediated anti-tumor responses by a mechanism that involved cell-to
      cell contact.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7621238
TI  - High-efficiency gene transfer and high-level expression of wild-type p53 in human
      lung cancer cells mediated by recombinant adenovirus.
AB  - A replication-defective and helper-independent recombinant p53 adenovirus was
      generated. The virus, Ad5CMV-p53, carries an expression cassette that contains
      human cytomegalovirus E1 promoter, human wild-type p53 cDNA, and SV40 early
      polyadenylation signal. Four human non-small-cell lung cancer cell lines
      representing differences in p53 configuration were used to evaluate the Ad5CMV
      p53 virus. In the H358 cell line, which has a homozygous deletion of p53, the p53
      gene was transferred with 97% to 100% efficiency, as detected by
      immunohistochemical analysis, when the cells were infected with Ad5CMV-p53 at a
      multiplicity of infection of 30 to 50 plaque-forming units/cell. Western blots
      showed that the p53 protein was expressed at a high level. The protein expression
      peaked at day 3 after infection and lasted for at least 15 days. Growth of the
      Ad5CMV-p53 virus-infected H358 cells was inhibited 79%, whereas that of
      noninfected cells or the cells infected with the control virus was not inhibited.
      Growth of cell line H322, which has a point mutation in p53, was inhibited 72% by
      Ad5CMV-p53, while that of cell line H460 containing wild-type p53 was less
      affected (28% inhibition). Tests in nude mice demonstrated that tumorigenicity of
      the Ad5CMV-p53-treated H358 cells was greatly inhibited. In a mouse model of
      orthotopic human lung cancer, the tumorigenic H226Br cells, with a point mutation
      in p53, were inoculated intratracheally 3 days before the virus treatment.
      Intratracheal instillation of Ad5CMV-p53 prevented tumor formation.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7621239
TI  - Viral vector systems for gene therapy.

PMID- 7621240
TI  - Antisense oligonucleotide technology in the development of cancer therapeutics.

PMID- 7621242
TI  - Transmission of endogenous VL30 retrotransposons by helper cells used in gene
      therapy.
AB  - Retrovirus-derived vectors and packaging cell lines are basic components used for
      gene transfer in human gene therapy. To eliminate recombinational and
      transcriptional problems associated with retroviral vectors, synthetic
      retrotransposon VL30 vectors were devised. During experimentation with these new
      vectors, extensive cotransmission of endogenous VL30 retrotransposon sequences
      was observed, originating within helper cell lines used in gene therapy
      experiments. The RNA was efficiently packaged into helper virus and was
      transmitted to recipient human cells, where it was again expressed as RNA.
      Transmission occurred regardless of whether the vector was retrovirus-derived or
      VL30, or if no vector was used. Endogenous VL30 RNA was readily detected in
      unselected recipient cells after a single exposure to helper virus, demonstrating
      a high efficiency of transmission compared with a cotransmitted VL30 vector,
      which contained an extensive deletion of internal sequences. These studies
      indicated that VL30 retrotransposons were ubiquitously transmitted by murine
      helper cells. Furthermore, the data strongly suggested that improvements in gene
      transfer may be obtained, both by using nonmurine helper cells (to reduce
      competitive inhibition by endogenous VL30) and by using VL30-derived vectors with
      intact packaging sequences.

PMID- 7621241
TI  - Enhanced cytotoxicity of antiviral drugs mediated by adenovirus directed transfer
      of the herpes simplex virus thymidine kinase gene in rat glioma cells.
AB  - The antiviral agents ganciclovir, 1-beta-D-arabinofuranosylthymine (araT),
      acyclovir, and 5-iodo-5'-amino-2',5'-dideoxyuridine were cytotoxic to rat C6
      glioma cells expressing retrovirally transferred herpes simplex virus (HSV) type
      1 thymidine kinase (TK) coding sequence, with concentrations that inhibited cell
      survival by 50% (IC50 values) of 0.06, 3, 13, and 23 mumol/L, respectively. In C6
      cells not expressing HSV-TK, the IC50 value for ganciclovir was 140 mumol/L and a
      concentration of 1 mmol/L killed more than 99% of the cells. The other antiviral
      agents tested were less toxic in nontransduced cells. Compared with retrovirally
      transduced cells, transduction of C6BU1 cells with an adenovirus vector
      containing the coding sequence for HSV-TK (Ad.RSVtk) increased the cellular
      activity of the viral kinase up to 600-fold with increasing multiplicity of
      infection (MOl). Cells transduced with Ad.RSVtk exhibited as much as a fivefold
      and 12-fold decrease in IC50 value for ganciclovir and araT, respectively,
      compared with retrovirally transduced cells. Sensitivity to antiviral drugs
      increased with increasing exposure to Ad.RSVtk, with IC50 values of 0.6 and 0.005
      mumol/L for araT and ganciclovir, respectively, at an MOl of 1000. These data
      suggest that adenoviral transfer of HSV-TK will allow the use of less toxic drugs
      or lower concentrations of toxic drugs such as ganciclovir for directed antitumor
      therapy in vivo.

PMID- 7621243
TI  - The frequency of major histocompatibility complex antigen abnormalities in
      urological tumours and their correction by gene transfection or cytokine
      stimulation.
AB  - There is increasing evidence that loss of major histocompatibility complex (MHC)
      antigens from tumors may be a factor in escape from immune surveillance. In an
      attempt to quantify this phenomenon in bladder tumors, frozen sections were
      stained immunochemically and cell lines were tested in a radiobinding assay
      before and after treatment with interferon gamma (IFN gamma) and after attempts
      to correct the defect by normal human leukocyte antigen (HLA) gene transfection.
      Study of 68 tumor sections with W6/32 antibody against monomorphic class I
      demonstrated that 42% had reduced or absent staining compared with the intensity
      of stromal staining. Ten percent of cases had complete absence with W6/32, all of
      which were also negative for beta 2-microglobulin (beta 2-m) expression. Use of
      polymorphic antibodies for A2, A3, Bw4, and Bw6 increased this frequency of
      defects to 73%. Study of 21 tumor cell lines with W6/32 demonstrated negative
      staining in five (23%) that could not be induced by IFN gamma and reduced
      staining in three (14%) that could be increased by IFN gamma, the remainder
      showing normal levels unaffected by IFN gamma. An additional six (28%) failed to
      express class II in response to IFN gamma, leading to an overall incidence of
      abnormality of 65%. In no case did cotransfection of one cell line with a defect
      in one case transfection of beta 2-m gene into a class I negative line of fully
      assembled MHC class I antigens. It is concluded that the majority of tumor cells
      demonstrate some form of MHC class I and II defects.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7621244
TI  - Safety testing programs for gene therapy viral vectors.

PMID- 7621245
TI  - Role of manganese superoxide dismutase in radioprotection using gene transfer
      studies.
AB  - Overexpression of manganese superoxide dismutase (MnSOD) has been postulated as
      one possible mechanism of radioprotection for hematopoietic cells. In this study
      retroviral constructs having the human MnSOD gene in both the sense and antisense
      orientations and the Neo-R gene as a selectable marker were transfected into the
      human erythroleukemic cell line K562 and the human melanoma cell line A375 by
      electroporation. Stably transfected K562 and A375 cells selected in G418 for 3
      weeks were subjected to various doses of irradiation, and cell viability was
      assayed using a colony assay system in semisolid medium. Results demonstrated
      that K562 cells transfected with MnSOD in the antisense orientation displayed
      increased sensitivity to irradiation compared to parental or vector-transfected
      K562 cells. In contrast, A375 cells transfected with the sense MnSOD gene
      demonstrated increased resistance to irradiation compared to parental or vector
      transfected A375 cells. The expression of the MnSOD gene in these transfected
      cell lines correlates with the up- or down-modulation of radiosensitivity. Thus,
      increased MnSOD protein was seen in the A375 cells containing the sense MnSOD,
      whereas decreased MnSOD protein was seen in the K562 cells containing the
      antisense MnSOD. These data provide evidence for the direct role of MnSOD in
      radioprotection using antisense gene transfer/inhibition studies.

PMID- 7621246
TI  - A retroviral vector expressing human interferon gamma upregulates MHC antigen
      expression in human breast cancer and leukemia cell lines.
AB  - The use of cytokines to modify antigen expression on syngeneic murine tumor cells
      has led to immunization of the host from subsequent challenges with the parent
      tumor cell line. To determine whether this approach can be applied to human
      malignancies we introduced the human interferon gamma gene (IFN gamma) into the
      human breast cancer cell lines MDA-MB-435 and MDA-MB-231 using retroviral
      mediated gene transfer. Retroviral transfer of the IFN gamma gene was associated
      with decreased growth, decreased tumor invasiveness, IFN gamma production, and
      upregulation of MHC antigens. While the MDA-MB-435 produced higher levels of IFN
      gamma than MDA-MB-231, MHC class I and class II antigens were upregulated in both
      cell lines. Introduction of this vector into the human leukemia cell line K562
      led to increased expression of MHC class I antigens, but not class II. Our
      findings suggest that expression of interferon gamma in breast cancer cells may
      lead to increased recognition of breast cancer cells by the host immune system.
      Furthermore, these data suggest that further development of this approach to
      cancer immunotherapy is warranted.

PMID- 7621247
TI  - Inhibition of p185c-erbB-2 proto-oncogene expression by antisense
      oligodeoxynucleotides down-regulates p185-associated tyrosine-kinase activity and
      strongly inhibits mammary tumor-cell proliferation.
AB  - The c-erbB-2 proto-oncogene codes for a 185-kd putative growth factor receptor
      that is highly homologous to but distinct from the epidermal growth factor (EGF)
      receptor. Amplification and overexpression of c-erbB-2 occurs in a number of
      human tumors, in some of which it is a negative prognostic factor. This study
      investigates the possibility of inhibiting tumor-cell proliferation by blocking c
      erbB-2 expression in the human mammary carcinoma cell line SK-Br-3 using
      chemically modified antisense oligodeoxynucleotides. Expression of the p185c-erbB
      2 protein product was selectively reduced within 48 hours and resulted in a
      growth arrest of SK-Br-3 cells. Biochemical studies of tyrosine-kinase and S6
      kinase activities after antisense inhibition of c-erbB-2 show that p185c-erbB-2
      activates the S6-kinase signalling pathway in a nonlinear, dose-dependent manner.
      This may be relevant for the design of therapeutic strategies involving the
      inhibition of c-erbB-2 (proto)- oncogene expression.

PMID- 7621248
TI  - Transduction of human melanoma cells with the gamma interferon gene enhances
      cellular immunity.
AB  - Human tumor cells transduced with the gamma interferon (gamma IFN) gene are
      currently used in specific active immunotherapy protocols to enhance the
      antitumor immune responses of cancer patients. This in vitro study was undertaken
      to examine the initial events in the cellular immune response that may occur
      following the administration of the gamma IFN-transduced cell vaccine. Human
      melanoma tumor cell lines were transduced with a MoMLV-based retroviral vector
      carrying the human gamma IFN gene. The transduced cells expressed the cytokine
      gene, secreted biologically active gamma IFN, and exhibited enhanced expression
      of MHC class I and class II (HLA-DR), and ICAM-1 surface antigens. The gamma IFN
      transduced and corresponding parental melanoma cells were used for the induction
      of short-term lymphocyte cultures. Peripheral blood lymphocytes or lymph node
      cells from 20 melanoma patients were stimulated for 5 to 15 days with autologous
      or MHC class I-matched allogeneic parental or gamma IFN-transduced melanoma
      cells. Seven of the 20 lymphocyte cultures showed substantial increases in lytic
      activity following stimulation with the transduced melanoma cells in comparison
      to control lymphocyte cultures stimulated with unmodified parental melanoma. The
      cytolytic activity stimulated with gamma IFN-modified melanomas was mediated
      partly by MHC-restricted cytotoxic T lymphocytes and partly by NK cells.
      Lymphocyte cultures that displayed increases in cytotoxicity after stimulation
      with the gamma IFN-transduced melanoma cells also exhibited enhanced expression
      or induction of one or more of the following lymphokines: IL-4, IL-1 alpha, IL-1
      beta, gamma IFN, and TNF-alpha.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7621249
TI  - Transfection of a nonactive site mutant murine DHFR cDNA (the tryptophan 15
      mutant) into Chinese hamster ovary and mouse marrow progenitor cells imparts MTX
      resistance in vitro.
AB  - Chinese hamster ovary (CHO) DHFR-cells were converted to the DHFR+ (dihydrofolate
      reductase) phenotype when transfected with a mammalian expression vector
      containing the murine mutant Trp15 DHFR cDNA. Transfection of the Trp15 DHFR cDNA
      into wild-type CHO cells resulted in resistance to high levels of methotrexate
      (MTX) in vitro indicating that this mutant DHFR cDNA can act as a dominant
      marker. Southern and Northern blot analyses of transfected cells indicated that
      the transfected mutant DHFR cDNA was integrated and expressed. Gene copy number
      analysis showed that the Trp15 cDNA was amplifiable in increasing concentrations
      of MTX. Transfection of murine bone marrow progenitor cells with the Trp15 mutant
      DHFR cDNA resulted in MTX resistant colony forming units-granulocyte macrophage.

PMID- 7621250
TI  - Molecular conjugate vectors mediate efficient gene transfer into gastrointestinal
      epithelial cells.
AB  - Transfer of genes to the gastrointestinal epithelium would be advantageous from
      investigational and therapeutic standpoints. Efficient transfer of DNA to the
      intestinal epithelial cells, however, has been problematic with conventional
      viral and nonviral vectors. As an alternative, we have utilized molecular
      conjugate vectors to transfer DNA to enterocytes via the receptor-mediated
      endocytosis pathway. We were able to achieve efficient transfection of
      transformed (Caco2 cells) and nontransformed gastrointestinal cells derived from
      neonatal piglets utilizing molecular conjugate vectors. Analysis of heterologous
      gene expression revealed that enterocytes could serve as a secretory cellular
      source of alpha 1-antitrypsin and factor IX. Transient expression of heterologous
      DNA persisted for up to 2 weeks following transfection. Our observations suggest
      that molecular conjugate vectors may represent a promising strategy in the
      transfer of genes to cells of the gastrointestinal tract.

PMID- 7621251
TI  - Papillomaviruses as targets for cancer gene therapy.
AB  - Gene therapy of human cancer is likely to be most effective when it is directed
      at targets that are expressed in cancer cells but are lacking from other cells.
      Human papillomaviruses can provide such targets, since these viruses are present
      in many cervical and oral cancers, and are likely to be etiological agents of the
      tumor. Continued expression of human papillomavirus genes is probably necessary
      for the growth of these cancers, and effective gene therapy could consist of
      antisense or ribozyme molecules directed against these genes. Some human
      papillomavirus gene products are antigenic, and immunotherapy based upon these
      antigens might prove clinically beneficial. Human papillomaviruses have specific
      promoters, are linked to toxin genes, the toxin may be selectively expressed by
      tumor cells where the virus genes are active. Thus, there are several approaches
      for the development of specific gene therapy for human cancers that contain human
      papillomaviruses.

PMID- 7621252
TI  - Suppression of tumorigenesis by transcription units expressing the antisense E6
      and E7 messenger RNA (mRNA) for the transforming proteins of the human papilloma
      virus and the sense mRNA for the retinoblastoma gene in cervical carcinoma cells.
AB  - Human cervical carcinoma cell lines that harbor human papilloma virus (HPV) have
      been reported to express HPV E6 and E7 proteins at least in the beginning stages
      if not at all stages of the disease. The HPV E6 and E7 proteins bind to and
      inactivate the products of the p53 and retinoblastoma (Rb) tumor suppressor
      genes, which thereby allow the cervical carcinoma cells to circumvent the action
      of these tumor suppressor genes. We observed that the introduction of the
      antisense HPV 18 E6 and E7 sequences, as well as a sense cDNA for the human wild
      type Rb gene into a human cervical carcinoma cell line (HeLa), which is positive
      for the HPV 18 provirus, decreased the in vitro and in vivo growth rate of the
      transfected cells if both antisense transcripts for the HPV 18 E6 and E7 and
      sense transcripts for human Rb were expressed. In addition, overexpression of a
      complementary DNA (cDNA) for the Rb messenger RNA was sufficient to slow the
      proliferation of HeLa cells, and the level of Rb cDNA expression was correlated
      with the degree to which the rate of growth of the tumor was slowed. The results
      of our experiments show that the presence of HPV E6 and E7 proteins and the
      resultant inactivation of Rb in cervical carcinoma cells contributes to the
      neoplastic phenotype even in highly evolved cervical carcinoma cell lines such as
      HeLa, which have been derived from a cervical carcinoma patient at an advanced
      stage of the disease process. These data suggest that the HPV proteins play a
      role not only at the beginning of cervical cancer, but also at advanced stages of
      this disease. These experiments may lead to genetic approaches to the control of
      this disease that involve antisense sequences that downregulate the E6 and E7
      genes or lead to expression of the Rb gene.

PMID- 7621253
TI  - A carcinoembryonic antigen polynucleotide vaccine for human clinical use.
AB  - We have constructed a plasmid DNA encoding the full-length complementary DNA for
      human carcinoembryonic antigen (CEA) under transcriptional regulatory control of
      the cytomegalovirus early promoter/enhancer (pCEA) and demonstrated that this
      plasmid can function as a polynucleotide vaccine to elicit a CEA-specific immune
      response. This immune response protects against tumor challenge with syngeneic
      CEA-transduced colon carcinoma cells in mice. In the present work, the pCEA
      construct and purification method were modified to eliminate nonessential viral
      sequences, the ampicillin selectable marker, mutagens, and endotoxin to produce a
      reagent suitable for human clinical trials. The human use plasmid (pGT37) directs
      CEA expression at levels comparable with the original pCEA plasmid and can be
      propagated to yield large quantities of plasmid DNA based on kanamycin selection.
      A simple extraction technique greatly reduces contamination by endotoxin. Six
      weekly intramuscular injections of pGT37 elicited CEA-specific lymphoblastic
      transformation and antibody response in five of five mice and fully protected 10
      of 10 mice against tumor challenge with syngeneic CEA-expressing colon cancer
      cells 42 days from the first plasmid injection. Thus, pGT37 encoding a tumor
      associated antigen (CEA) has been shown to elicit cellular and humoral immune
      responses and mediate antitumor effects in vivo. This plasmid is suitable for
      human use and can be easily propagated in the laboratory.

PMID- 7621254
TI  - Antisense approaches to cancer gene therapy.
AB  - Recent advances in the use of oligodeoxynucleotide and plasmid-derived RNA as
      antisense agents of special relevance to cancer gene therapy are summarized with
      emphasis on agents and systems which have lead to clinical trials and/or
      regression of established tumors in animal model systems. Transformed cell lines
      bearing plasmids and viruses designed for the transcription of antisense RNA have
      the advantage that they can be characterized thoroughly and the effects of
      antisense RNA on target gene expression and phenotype can be studied easily in
      vivo. Promising results make the considerable efforts of applying
      oligodeoxynucleotides in whole animals and in clinical trials more plausible.
      Conversely, oligodeoxynucleotide experiments which yield promising results in
      tissue culture can be generalized to the in vivo setting by development of clones
      of cells bearing plasmid-derived antisense RNA against the same target. Several
      examples of the concordant results for oligodeoxynucleotide and plasmid-derived
      antisense RNA against the same target are considered. The importance of
      examination of antisense effects in syngeneic and immunocompetent hosts is
      illustrated by studies of insulin-like growth factor and insulin-like growth
      factor receptor where tumor regression and protection against tumor formation
      have been observed for particular cell types in defined settings.

PMID- 7621255
TI  - Cancer gene therapy clinical trials.

PMID- 7621256
TI  - Synthetic recombinant DNA delivery for cancer therapeutics.

PMID- 7621257
TI  - Apoptosis induced in human osteosarcoma cells is one of the mechanisms for the
      cytocidal effect of Ad5CMV-p53.
AB  - Recombinant adenovirus Ad5CMV-p53 induced a strong cytocidal effect in Saos-LM2
      cells. This cell line, derived from human osteosarcoma Saos-2 cells, has a
      homozygous deletion of the p53 gene. By using immunocytochemical and Western blot
      analyses, we demonstrated that Ad5CMV-p53 effectively infected Saos-LM2 cells at
      multiplicities of infection of 10 to 50 plaque-forming units/cell and mediated a
      high-level expression of the exogenous wild-type p53 protein in the cells. Growth
      of the infected cells was greatly suppressed whereas that of mock- or control
      virus-infected cells was not. Because wild-type p53 induces apoptosis in certain
      types of cells, we studied DNA fragmentation in situ in the Ad5CMV-p53-infected
      Saos-LM2 cells by terminal deoxynucleotidyl transferase assays, which yielded
      positive nuclear staining. Further analysis of the Ad5CMV-p53-infected Saos-LM2
      cells by light and electron microscopy demonstrated that the cells underwent the
      characteristic morphological changes of apoptosis such as plasma-membrane
      blebbing, nuclear condensation, and fragmentation. These changes were not
      observed in mock- or control virus-infected cells. Our results on Saos-LM2 cells
      indicate that apoptosis induced by Ad5CMV-p53 may be one of the mechanisms
      underlying the cytocidal effect of Ad5CMV-p53.

PMID- 7621258
TI  - Transduction of normal and malignant oral epithelium by an adenovirus vector: the
      effect of dose and treatment time on transduction efficiency and tissue
      penetration.
AB  - We tested an adenovirus vector that carries a beta-D-galactosidase marker gene
      for its ability to transduce normal oral mucosa and oral carcinoma cells. Topical
      application of adenovirus to normal oral mucosa of mice at 1 x 10(10) plaque
      forming units (pfu)/mL for 1 minute did not result in transduction of epithelial
      cells. Similarly, topical application to human oral mucosa ex vivo was not
      successful. However, systemic administration by intracardiac injection of
      hamsters did transduce normal oral mucosa effectively. To evaluate transduction
      of carcinomas, the Tu138 human oral cancer cell line was used. A single
      application of virus at 1 x 10(8) pfu/mL in vitro resulted in 30% of oral
      carcinoma cells expressing the marker gene, and 2 x 10(8) pfu/mL transduced 60%
      of cells. After two applications of virus at 2 x 10(8) pfu/mL with an interval of
      18 hours, 100% of oral carcinoma cells expressed the marker gene. Topical
      application to a raft culture of Tu138 cells for 1 hour produced gene expression
      that penetrated up to four layers of cells. To emulate the effect of treating a
      carcinoma, Tu138 cells were implanted subcutaneously in nude mice, allowed to
      grow to a tumor 1 cm in diameter, and then injected directly with virus. This
      produced diffuse transduction of around 30% of cells in the tumor, and expression
      was seen in cells at a significant distance from the injection site. Adenovirus
      vectors are therefore capable of transferring novel genetic information to both
      normal and malignant oral mucosa. They may have potential for use in gene therapy
      in the prevention or treatment of oral squamous carcinomas.

PMID- 7621259
TI  - Increased in vitro and in vivo tumoricidal activity of a macrophage cell line
      genetically engineered to express IFN-gamma, IL-4, IL-6, or TNF-alpha.
AB  - Genetically engineered monocytes and macrophages may have potential as effector
      cells for the adoptive immunotherapy of cancer. As a first step, we have
      transfected the genes encoding either mouse interferon (IFN)-gamma, human
      interleukin (IL)-6, mouse IL-4, or mouse tumor necrosis factor (TNF)-alpha into
      the mouse macrophage cell line, J774A.1 cells using retroviral vectors. In vitro
      activation of J774A.1 cells by gene modification was assessed by morphological
      changes, proliferative activity was determined by [3H]-TdR uptake, and cytolytic
      activity was assessed using an 18-hour chromium-51 (51Cr) release assay. In vivo
      tumoricidal activity was studied by means of local adoptive immunotherapy using
      intratumoral injection of transfected effector cells. IFN-gamma gene-transfected
      J774A.1 [J7(IFN-gamma)] cells developed filamentous processes, increased doubling
      times, and enhanced tumoricidal activity against three tumor cell lines: the TNF
      sensitive fibrosarcoma line WEHI 164 and the TNF-alpha-resistant cell lines B16
      melanoma and C1300 neuroblastoma. IL-6-, TNF-alpha-, and IL-4-gene-transfected
      J774A.1 cells also had augmented tumoricidal activity but did not display any
      changes in morphology or growth. Cytolytic activity was markedly reduced after
      the addition of anti-TNF-alpha antibodies. Cytolytic J7(IFN-gamma) cells showed
      upregulated expression of TNF-alpha messenger RNA. After intratumoral injection
      of J7(IL-4) and J7(IFN-gamma) cell mixtures, 50% of established B16 melanomas
      were rejected by C57BL/6 mice, thereby demonstrating synergistic killing. Further
      studies on gene-transfected macrophages should better define their potential
      usefulness in tumor immunotherapy.

PMID- 7621260
TI  - Genetically marking human cells--results of the first clinical gene transfer
      studies.
AB  - The rapid development of both knowledge and techniques in molecular biology have
      made it possible to engineer genetic constructs and transfer them into cells of
      individuals with various diseases. Such gene therapies may alleviate or perhaps
      even cure diseases for which no adequate treatment now exists. One potential
      application is to treat genetic disease by inserting a normal gene into cells in
      individuals with a "malfunctioning" gene. The added genetic information could
      allow these cells to function properly and might reduce or eliminate the sequelae
      of the disease. Such genetic manipulation could also be used to combat other
      diseases using the same general technique. For example in cancer patients,
      various cytokine genes inserted into tumor cells may serve as components of a
      tumor vaccine because such cytokine-secreting tumor cells can induce a
      significant T-cell response in experimental animal models when compared with non
      gene-modified tumors, ultimately leading to a systemic immune response. In
      addition to treating patients, transferred genes also can serve as markers to
      obtain important information about the fate of otherwise indistinguishable cells.
      For example, we used a genetic marker to label tumor-infiltrating lymphocytes
      (TILs) to monitor their in vivo survival and ability to "home" to tumor sites.
      Gene markers also were transferred into autologous bone marrow cells to study the
      mechanism of tumor relapse. This review will focus primarily on studies using
      gene markers to track TILs after transfer. We will focus on the following issues:
      (a) that TILs are potent antitumor cells, mediating partial and complete
      responses in patients with melanoma; (b) the importance of the initial gene
      marked TIL study; (c) safety considerations in the use of gene marking/gene
      therapy; (d) results of gene-marked TIL studies; and (e) other gene-marked cells.

PMID- 7621262
TI  - Recombinant adenovirus-mediated gene transfer to genitourinary epithelium in
      vitro and in vivo.
AB  - Transitional cell carcinoma (TCC) of the bladder is associated with characterized
      lesions in dominant and recessive oncogenes. The understanding of the molecular
      basis of tumorigenesis in these instances makes possible the application of gene
      therapy strategies for TCC. In this regard, the ability to directly access the
      epithelium of the genitourinary (GU) tract via the urethra provides a practical
      means to implement these various gene therapy approaches. We thus explored vector
      strategies to accomplish direct in vivo transduction of GU epithelium. Initially,
      three human (HT 1197, HT 1376, T24) and one mouse (MBT-2) TCC cell lines were
      transduced using a recombinant adenoviral vector expressing the firefly
      luciferase reporter gene, rAd-CMV-Luc. In these studies, reporter gene expression
      was found to be significantly elevated above background for all four cell lines.
      Of note, the TCC cell lines HT 1197 and HT 1376 showed expression levels
      comparable with the cervical carcinoma cell line HeLa, a cell line previously
      shown to be highly susceptible to recombinant adenovirus-mediated gene
      transduction. An in vitro time course for T24 and MBT-2 using rAd-CMV-Luc showed
      peak expression 1 day after transduction for the T24 line and 3 days after
      transduction for the MBT-2 line, with detectable levels of expression persisting
      for at least 7 days. As a next step, human and mouse primary tissue deriving from
      the GU epithelium were transduced using rAd-CMV-Luc. In this assay, luciferase
      expression levels significantly above background were observed in both
      instances.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7621261
TI  - Toxicity studies and distribution dynamics of retroviral vectors following
      intrathecal administration of retroviral vector-producer cells.
AB  - The use of intrathecal, retroviral-mediated transfer of the herpes simplex
      thymidine kinase (HStk) gene and subsequent ganciclovir (GCV) administration has
      recently been shown to improve survival in a rat model of leptomeningeal
      carcinomatosis. Clinical application of this approach is attractive because
      access to the cerebrospinal fluid (CSF) space is relatively noninvasive and
      distribution of producer cells and vectors may be facilitated by circulation of
      CSF, overcoming distribution problems inherent in solid tumors. However,
      meningeal inflammation, transduction and injury to normal CNS tissue,
      proliferation of the xenogeneic producer cells in the subarachnoid space, immune
      mediated injury, and development of hydrocephalus are possible complications of
      intraventricular or intrathecal administration of vector-producer cells. In
      addition, the dynamics of producer cell and vector distribution in the CSF are
      unknown. To address these issues, we evaluated the safety of this approach for
      gene delivery and assessed the dynamics of distribution of producer cells and
      retroviral vectors in rats and non-human primates. In rats, transduction of
      normal central nervous system (CNS) structures surrounding the subarachnoid space
      was evaluated after intrathecal and intraventricular injections of beta
      galactosidase and HStk vector-producer cells, with and without GCV. In primates,
      beta-galactosidase and HStk vector-producer cells were injected
      intraventricularly and GCV was administered either intrathecally or
      intravenously. Toxicity was evaluated by neurologic examination, serial
      gadolinium-enhanced MRI scans of the brain, and blood and CSF profiles. A
      subgroup of monkeys received repeated intraventricular injection of vector
      producer cells and intravenous GCV. The titer of retroviral-vector was measured
      in cisternal and lumbar CSF samples after repeated producer cell
      injection.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7621263
TI  - [Diagnostic value of duodenal drainage in patients with biliary symptoms and
      negative imaging test].
AB  - A group of patients with clinical manifestations suggesting biliary origin in
      whom diagnostic imaging techniques were negative were studied by duodenal biliary
      drainage with the aim of identifying whether microcalculi were present in the
      bilis being responsible for the symptomatology. The problem group was made up of
      96 patients with the results being compared with those of a control group
      (without biliary disease) including 45 subjects. Duodenal biliary drainage was
      analyzed for the detection of microlithiasis in the biliary sediment in all the
      subjects. The analysis was positive in 46 (47.9%) of the patients with biliary
      clinical manifestations while analysis was positive in only 5 (11.2%) of the
      control group with the differences being statistically significant. Seventeen of
      the 46 positive patients underwent surgery demonstrating biliary disease in all
      (chronic cholecystitis). All these patients remained asymptomatic except one on
      follow up with 94.1% cure by cholecystectomy being achieved. The authors conclude
      that duodenal biliary drainage is a highly profitable, complication-free and
      easily performed diagnostic technique for the detection of microlithiasis which
      should be regularly used in patients with symptoms suggestive of biliary origin
      and complementary negative explorations.

PMID- 7621264
TI  - [Pseudomyxoma peritonei].
AB  - Pseudomyxoma peritonei is an infrequent clinical entity, characterized by
      peritoneal implantations organized in cyst of mucine or free peritoneal mucine.
      Most arise from cystadenoma or cystadenocarcinoma of the ovary and appendix, and
      fewer from other tumours and locations. It is more common in females, and it is
      usually diagnosed over the fifth decade. Three cases of pseudomyxoma peritonei
      are presented, two associated to appendicular carcinoma and one to carcinoma of
      the ovary, and the data published about this disease are reviewed.

PMID- 7621265
TI  - [Tuberculous splenic abscess in an immunocompetent patient].
AB  - Splenic tuberculosis is a rare entity. The case of an 18-year old patient
      admitted for fever and general malice is described. Echography and abdominal CT
      showed a hypodense image localized in the spleen. Splenic tuberculosis was
      diagnosed upon observation of alcohol acid resistant bacilli (AARB) in the biopsy
      obtained by punction of the abscess. Correct tuberculostatic treatment led to
      disappearance of the splenic abscess with no further therapeutic measures being
      required.

PMID- 7621266
TI  - [Acute renal failure associated with 5-aminosalicylic acid in inflammatory bowel
      disease].
AB  - A case of acute renal failure with characteristics of interstitial nephritis
      associated to treatment with mesalazine (5-ASA bound to resin) in a 26-year old
      patient with a 7-year history of Crohn's disease is presented. The patient had
      been previously treated with 5-ASA with no alterations in renal function being
      observed. Renal failure became manifest several days after initiation of
      maintenance therapy with 5-ASA during the latest outbreak of intestinal
      inflammatory disease and disappeared upon suppression of the drug.

PMID- 7621268
TI  - [Does hepatitis E exist in Europe?].

PMID- 7621267
TI  - [Epithelioid hemangioendothelioma: a rare indication for liver transplantation?].
AB  - A clinical case of epithelioid hemangioendothelioma without extrahepatic
      involvement treated with liver transplantation is presented. The patient remains
      alive 42 months thereafter without tumor recurrence. A review of cases reported
      to date was carried out with special reference being made to the therapy
      undertaken and the follow-up.

PMID- 7621269
TI  - [Diagnostic usefulness of bile microscopy].

PMID- 7621271
TI  - [Vascular ectasia of the antrum].

PMID- 7621272
TI  - [Vascular ectasia of the antrum].

PMID- 7621270
TI  - [The mediators of inflammation and chronic hepatitis].

PMID- 7621273
TI  - [Hepatitis C virus infection and porphyria cutanea tarda].
AB  - The prevalence of antibodies versus the hepatitis C virus (antiHCV) was studied
      in a group of 10 patients diagnosed with porphyria cutanea tarda (PCT) and the
      possible existence of subclinical forms of PCT was determined in 64 patients with
      chronic anti HCV positive liver diseases. The prevalence of anti HCV was found to
      be 40% in patients with PCT. In the group of patients with chronic anti HCV
      positive liver disease only one patient (1.5%) presented an increase in the
      urinary elimination of porphyrias in the absence of cutaneous lesions of
      photosensitivity. This study confirms the importance of the hepatitis C virus as
      a triggering agent of PCT. These results demonstrate the existence of a low
      prevalence of subclinical forms of PCT among patients with chronic anti HCV
      positive liver diseases.

PMID- 7621274
TI  - [Lansoprazol].

PMID- 7621275
TI  - [Endoscopic gastrointestinal findings in patients with human immunodeficiency
      virus infection].
AB  - From January 1992 to August 1993, 150 endoscopies (114 fiber gastroscopies, 29
      fiber colonoscopies and 7 CPRE) were carried out in a total of 142 anti HIV
      positive patients. The most frequent clinical manifestations leading to the
      exploration were dysphagia, epigastric pain, diarrhea and upper or lower
      gastrointestinal bleeding. Endoscopic alterations were observed in most of the
      exploration although specific diagnosis was only achieved in approximately one
      third of the patients with the most frequent being esophagitis by Candida and CMV
      (21% and 5%, respectively in the fiber gastroscopies performed). Digestive
      manifestations were varied in the patients in whom esophagitis by Candida was
      diagnosed while dysphagia and diarrhea were the symptoms commonly observed in the
      patients with esophagitis or colitis by CMV. The diagnostic profitability of
      endoscopy was high in patients presenting dysphagia, diarrhea, gastrointestinal
      bleeding or in those in whom endoscopy was performed for tumoral staging or to
      evaluate the possible existence of manifestations secondary to the presence of
      portal hypertension.

PMID- 7621276
TI  - [Estrogen and progestagen treatment in digestive hemorrhage caused by vascular
      malformations].
AB  - The efficacy of an association of estrogens and progestagens in the treatment of
      gastrointestinal bleeding by angiodysplasia was analyzed. Thirty-three patients
      with gastrointestinal bleeding due to vascular malformations were admitted from
      January 1986 to December 1993. Fifteen of the 33 patients were submitted to
      surgical or endoscopic treatment. The remaining 18 patients underwent daily oral
      treatment with a combination of estrogens-progestagens containing 2.5 mg of
      lynestrenol and 0.075 mg of mestranol. One patient presented a venous thrombosis
      leading to suppression of treatment at one month of initiation. The 17 remaining
      patients were treated for a mean of 22 +/- 4 months (range: 3-60). During
      treatment 13 of the 17 patients (76%) did not present evidence of hemorrhage.
      Likewise, the number of hemorrhagic episodes per year decreased from 4.4 +/- 1.2
      prior to treatment to 0.7 +/- 0.5 during treatment (p < 0.05) with transfusional
      requirements decreasing from 7.9 +/- 2.8 erythrocyte concentrates per year prior
      to treatment to 1.2 +/- 1.0 during treatment (p < 0.05). In conclusion, the
      combined treatment with estrogens and progestagens prevents recurrence of
      gastrointestinal bleeding by angiodysplasia.

PMID- 7621277
TI  - [A comparative randomized controlled study of the efficacy of interferon alfa-2b
      and interferon alfa-2a in the treatment of chronic hepatitis C].
AB  - Interferon (INF) is the treatment of choice in active chronic hepatitis C
      although the optimum therapeutic schedule remains undefined to date. One forty
      eight patients with active chronic hepatitis C were included in a randomized
      controlled study to compare the therapeutic efficacy of 2 types of recombinant
      alpha IFN: alpha-2b IFN and alpha-2a IFN. Twelve patients were excluded from the
      study for different reasons. The groups were made up of 34 untreated patients
      (group I), 68 patients treated with 5 MU of alpha-2b IFN three times per week for
      12 months (group II) and 32 patients with 6 MU of alpha-2a IFN three times per
      week for one year (group III). On finalization of the treatment 39 patients from
      group II (57%) and 20 (63%) from group III showed normal transaminases (p > 0.05)
      while this was not so in any patient from group I (p < 0.001). HCV infection of
      less than 5 years was significantly associated with complete biochemical
      response. During the post treatment follow up (16.2 +/- 11.1 months; range: 6-45
      months) the transaminase levels reelevated in 26 (67%) responding patients from
      group II and in 12 (60%) patients from group III (p > 0.05). Therefore complete
      biochemical response was maintained in only 12 (19%) of the patients from group
      II and in 8 (25%) of the patients from group III (p > 0.05). Liver biopsy was
      carried out in the 3 post treatment months in 15 patients from group I, 29 from
      group II and 18 patients from group III with all the rebiopsied patients from
      groups II and III having demonstrated complete or partial response to
      IFN.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7621278
TI  - [Portacaval H-graft shunt as an alternative long-term treatment in
      gastrointestinal hemorrhage caused by esophagogastric varices].
AB  - From 1984 to 1991, 44 cirrhotic patients with gastrointestinal bleeding by
      esophagogastric varices (EGV) underwent emergency or elective calibrated
      portacaval shunt (CPS) with a prothesis of small diameter (8 and 10 mm) due to
      the impossibility of bleeding control by other conservative methods. In this
      series this procedure was found to be an effective alternative with acceptable
      operative mortality (20.4%), and a high rate of hepatic portal flow maintenance
      (72.2%) although a high incidence of postoperative hepatic encephalopathy (38.6%)
      of easy control was observed. The global probability of survival at 12 and 24
      months was 74 and 64%, respectively. Survival at one and 2 years was
      significantly higher in patients of Child score A than those of score B (94 and
      88% versus 73 and 56%). Patients of Child score C all died by the end of the
      first month thus suggesting that CPS should be performed in patients with good
      liver function (Child scores A and B).

PMID- 7621279
TI  - [Gastrointestinal hemorrhage secondary to heterotopic jejunal pancreas].
AB  - A case of heterotopic pancreas located in the small intestine is herewith
      presented. The 19-years male patient had been admitted three times since 1991 for
      an anemic syndrome secondary to melena. The origin of the hemorrhage was not
      determined with the studies performed (intestinal transit, opaque enema,
      esophagogastroscopy, colonoscopy and gammagraphy with technetium 99). On the last
      admission a vascular lesion low flow was observed on arteriography of the upper
      mesenteric artery on the mesenteric edge of the proximal jejunum. Following
      laparotomy a small tumor was found in the jejunum and 5 cm of the intestine
      including the tumor was resected. The anatomic pathologic results demonstrated a
      heterotopic pancreas.

PMID- 7621280
TI  - [Carcinosarcoma of the gallbladder].
AB  - The authors present a case of carcinosarcoma of the gallbladder, discussing its
      possible histological origin, clinical picture, and recommended therapeutic
      approaches. Only 30 cases have so far been reported. The case described was seen
      because of a painless large volume mass in the right hypochondrium. She was
      surgically treated with a complete resection of the gross tumor including a
      portion of choledochus, followed by chemotherapy. The survival was of 20 months.

PMID- 7621281
TI  - [Ehlers-Danlos syndrome with giant duodenal diverticulum as a cause of
      cholangitis].
AB  - The case of a patient with the Ehlers-Danlos syndrome who presented a picture of
      acute cholangitis only attributable to the presence of a large duodenal
      diverticulum is reported. The pathologic implications of the duodenal diverticula
      are described with special attention being given to their participation in the
      development of acute cholangitis. The digestive manifestations associated to the
      Ehlers-Danlos syndrome are also reviewed.

PMID- 7621282
TI  - [Giant gastric and duodenal trichobezoar. Presentation of a case and review of
      the literature].
AB  - The case of a giant trichobezoar of 2.500 g in weight observed in a 26-year old
      woman with paranoid disorder which led her to trichophagia is presented. A review
      of the literature was carried out with the different etiopathogenic theories and
      proposed treatments being discussed.

PMID- 7621283
TI  - [Somatostatin and biliary lithogenesis].

PMID- 7621284
TI  - [Rejection of the liver graft].

PMID- 7621285
TI  - [A low prevalence of antibodies to the hepatitis C virus in stable heterosexual
      couples].
AB  - The prevalence of antibodies against the hepatitis C virus (HCV Ab) was studied
      in a group of 126 stable heterosexual couples of HCV Ab carriers. Only 1.59% of
      the couples was positive with no significant differences observed with regard to
      the prevalences seen in donors from the same area. The HCV Ab positive couples
      had shared toiletry articles but no other risk factors were detected. The authors
      conclude that the sexual transmission of the HCV is scarce.

PMID- 7621286
TI  - [Can a selenium deficiency affect the pathogenesis of cholestasis in pregnancy?].
AB  - In search of an environmental factor which modulates the expressivity of
      cholestasis of pregnancy and explains the seasonal and annual variations observed
      in Finland and Chile, the authors measured selenium (Se) concentration in the
      plasma and erythrocytes by atomic absorption spectrophotometry and the activity
      of the glutation peroxidase enzyme dependent on Se (GSH-Px) by a
      spectrophotometric method in 10 patients with cholestasis of pregnancy, 22 normal
      pregnant women, 43 non pregnant women and in 15 men, all of whom had normal
      weight/height, and similar ages, ethnic and geographic origin. Blood samples were
      obtained weekly from the pregnant women during the third trimester and 24-72
      hours postpartum. RESULTS: In non pregnant women and in men plasma Se was 0.83 +/
      0.02 mumol/l (range 0.6-1.2) and the GSH-Px activity was 306 +/- 5 U/L (range
      203-459). Both parameters were correlated and were similar to those of other
      populations whose ingestion of Se is low (Finland, New Zealand, and certain
      regions of China). In normal pregnant women studied between weeks 20 and 32, the
      plasma Se and GSH-Px activity were lower than in non pregnant women (0.71 +/-
      0.02 mumol/l and 260 +/- 5 U/l, respectively) with both progressively decreasing
      at the end of pregnancy and rapidly recovering post partum. The erythrocytic GSH
      Px activity was similar in normal pregnant women than in non pregnant women (27.7
      +/- 0.8 versus 28.1 +/- 0.6 U/g Hb). In patients with cholestasis of pregnancy,
      plasma and erythrocytic Se and GSH-Px activity were lower than in normal pregnant
      women (p < 0.05 in similar stages of pregnancy).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7621287
TI  - [The endoscopic treatment of postcholecystectomy biliary leakage].
AB  - Although there is a decrease in the total number of complications observed on
      performance of laparoscopy cholecystectomy (LC) there does appear to be an
      increase in biliary tract lesions. Seven cases of postcholecystectomy biliary
      leakage treated with endoscopic methods are presented. These cases include 4
      patients with leakage from the cystic canal stump and 3 with leakage from the
      common bile duct. In 5 cases the biliary tract lesion occurred following LC, 1
      after conventional cholecystectomy and in 1 reconverted LP. CPRE identified the
      site of the leakage in the 7 patients and in 2 residual choledocholithiasis. In 5
      cases treatment consisted in endoscopic papillotomy and placement of biliary
      endoprosthesis while only papillotomy was performed in 2 patients. In one of
      these cases CPRE was repeated and the sphincterotomy widened due to persistence
      of the leakage at 5 days, with the same finally closing at 15 days of the second
      CPRE. Closure of the biliary leakage was obtained in the other 6 cases in less
      than 72 hours post-CPRE. No complications secondary to the technique were
      observed. It was concluded that CPRE together with endoscopic papillotomy and
      placement of biliary prostheses is an effective and safe treatment for
      postcholecystectomy biliary leakages of the common bile duct or cystic duct.

PMID- 7621288
TI  - [Gastric tuberculosis: a report of 2 cases].
AB  - Two patients with gastric tuberculosis are described. The first presented toxic
      syndrome, multiple abdominal adenopathies, microcytic anemia and a subcardial
      ulcer with malignant characteristics at endoscopy. Diagnosis was based on the
      positivity of Ziehl-Neelsen staining and on the growth of Mycobacterium
      tuberculosis in the culture of the gastric mucosa. The second patient presented
      toxic syndrome, fever and a miliary pattern on thoracic radiography. Endoscopy
      demonstrated an ulcerated nodular lesion with granulomas with acid alcohol
      resistant bacillus being observed on biopsy. Mycobacterium tuberculosis was found
      in both the sputum and bronchoaspirate. The evolution of both cases was favorable
      with specific treatment.

PMID- 7621289
TI  - [Hepatic angiosarcoma: a report of a case associated with treatment with arsenic
      salts and a review of the literature].
AB  - Hepatic angiosarcoma is an infrequent neoplasm representing 1-3% of all the
      primary liver cancers. One fourth of the cases have demonstrated a relation with
      chemical carcinogens with the most frequent being thorium dioxide (thorotrast)
      and vinyl chloride. The case of an hepatic angiosarcoma which presented as an
      intraperitoneal hemorrhage in a patient who had undergone treatment with
      Neosalvarsan (dioxidiaminoarsenobenzol) 46 years beforehand is reported. The
      previous published reports include 6 cases of hepatic angiosarcoma related with
      treatment with arsenic salts and 4 cases in whom exposure was environmental.

PMID- 7621290
TI  - [Self-limited steatorrhea and chronic autoimmune hepatitis type I. The Group for
      the Study of Viral Hepatitis and AIDS].
AB  - Active chronic hepatitis is very infrequent in Spain. Its autoimmune pathogenesis
      is supported by the coexistence of autoimmune features, its usually good response
      to immunosuppressive treatment and the frequent coexistence of other processes of
      autoimmune etiology. The infrequent cases of steatorrhea observed may usually be
      found in the presence of severe colostasis or in association with other diseases
      such as celiac disease. The presence of sever anemia is also infrequent being
      observed on hemolysis of digestive bleeding. A case of autoimmune type I chronic
      hepatitis observed in a 14-year old woman presenting as acute hepatitis
      associated to severe anemia (Hb, 6,3 g/dl) and self-limited steatorrhea
      independent of the clinical course of the hepatic picture (stool fats of up to
      100 g/24 h) with no evidence of hemolysis, digestive bleeding, obvious
      colostasis, drug ingestion or demonstrable intestinal or pancreatic disease. The
      coexistence of these unusual findings led the authors to report this case.

PMID- 7621291
TI  - [Intracranial hypertension in severe acute liver failure].

PMID- 7621292
TI  - [Nonsteroidal anti-inflammatory agents and gastrointestinal pathology].

PMID- 7621294
TI  - [The effect of pregnancy on the course of chronic hepatitis C].

PMID- 7621293
TI  - [Misoprostol].

PMID- 7621295
TI  - [Tuberculous peritonitis: the diagnostic value of adenosine deaminase (ADA) in
      the ascitic fluid].

PMID- 7621296
TI  - Plasma lipoproteins and coronary heart disease.

PMID- 7621297
TI  - Postprandial lipoproteins and coronary heart disease.
AB  - Postprandial lipaemia, whether measured using levels of triglyceride of retinyl
      palmitate, is more severe in patients with coronary heart disease; however,
      little improvement in the discrimination between individuals with and without
      coronary heart disease can be made using postprandial measurements rather than
      measuring levels of high-density-lipoprotein2 cholesterol of apolipoproteins B.
      Retinyl palmitate levels occasionally reveal differences not apparent from
      triglyceride measurements. Elevated fasting and postprandial triglyceride levels
      may produce clinical disease partly by enhancing coagulation and by interfering
      with fibrinolysis.

PMID- 7621299
TI  - Biological importance of low-density-lipoprotein subfractions.
AB  - Low-density lipoproteins (LDLs) exist as discrete subfractions that vary in size
      and density. A predominance of small, dense LDLs is seen in patients with
      ischaemic heart disease and non-insulin-dependent diabetes, and is more common in
      men than in women. Because small, dense LDLs are associated with increased levels
      of triglycerides and low levels of high-density-lipoprotein cholesterol, their
      exact role as an independent cardiovascular risk factor is unknown. These
      lipoproteins exhibit abnormal characteristics, however, such as increased
      susceptibility to oxidation and decreased LDL receptor binding, which may result
      in increased atherogenicity.

PMID- 7621298
TI  - Atherogenicity of triglyceride-rich lipoproteins.
AB  - The measurement of plasma triglyceride levels further refines the estimation of
      the risk of coronary heart disease in patients with either high levels of low
      density-lipoprotein cholesterol or a high ratio of low-density-lipoprotein to
      high-density-lipoprotein cholesterol. Plausible mechanisms underlying the role of
      triglyceride-rich lipoproteins in the pathogenesis of coronary heart disease
      include the lipid loading of macrophages and accelerated thrombosis resulting
      from increases in both procoagulant and antifibrinolytic activity. Further
      research should include methods for better quantifying atherogenic subspecies of
      triglyceride-rich lipoproteins and intervention studies designed to assess the
      effect on the occurrence of coronary heart disease of lowering triglyceride or
      increasing HDL-cholesterol levels.

PMID- 7621300
TI  - Lipoprotein (a).
AB  - Our understanding of the pathophysiological role of lipoprotein (a) in
      cardiovascular disease and its clinical importance has improved, but there are
      still gaps in our knowledge and analytical performance that hinder the
      appropriate management of patients. Further information about the physiological
      functions of lipoprotein (a), if any, and its interactions with other risk
      factors is required.

PMID- 7621301
TI  - High-density lipoproteins and coronary heart disease.
AB  - High-density lipoproteins (HDLs) play an important role in the process of reverse
      cholesterol transport, the pathway by which the cholesterol in extrahepatic
      tissues is transported through plasma to the liver for recycling or for excretion
      from the body in bile. The concentration of HDL cholesterol is a powerful inverse
      predictor of the development of coronary heart disease, leading to a widely held
      view that HDL protects against the development of atherosclerosis. The mechanism
      by which HDLs protect is unknown. To date, no studies have been designed
      specifically to test the proposition that increasing the concentration of HDL
      cholesterol translates into a reduction in coronary risk. Nevertheless, in a
      subgroup of the Helsinki Heart Study, it was found that a substantial proportion
      of the beneficial effect of gemfibrozil was explicable in terms of an increase in
      the concentration of HDL cholesterol.

PMID- 7621302
TI  - The association between heart rate and blood pressure, blood lipids and other
      cardiovascular risk factors.
AB  - BACKGROUND: Several studies have shown that an elevated heart rate is associated
      with an increased risk of ischaemic heart disease. The aim of this study was to
      examine the relationship between heart rate, blood pressure, blood lipids and
      other cardiovascular risk factors in middle-aged men. METHODS: A total of 7735
      men, aged 40-59 years at screening, were selected at random from one of the
      general practices in each of the 24 towns participating in the cross-sectional
      (screening) phase of the British Regional Heart Study. Blood pressure and levels
      of blood lipids (serum total cholesterol, high-density-lipoprotein (HDL)
      cholesterol and triglycerides) and blood glucose were measured. RESULTS: All men
      with pre-existing evidence of ischaemic heart disease and those on regular
      antihypertensive treatment were excluded from the analysis. In the remaining 5597
      men, heart rate showed a strong positive correlation with cigarette smoking and
      body-mass index and decreased significantly at higher levels of physical activity
      and FEV1 (forced expiratory volume in 1 s). These associations remained
      significant after adjustment for each other. Age, alcohol intake and social class
      were not independently associated with heart rate. There was a significant
      positive association between heart rate and systolic and diastolic blood
      pressures, levels of blood cholesterol, triglycerides and blood glucose and a
      significant inverse association between heart rate and HDL-cholesterol levels,
      even after adjusting for the above confounding factors. After further adjustment
      for each of the other physiological variables, heart rate remained independently
      associated with diastolic and systolic blood pressures and levels of
      triglycerides and blood glucose. The relationship between heart rate and levels
      of total cholesterol and HDL cholesterol appeared to be secondary to its
      association with triglyceride levels. The association between body-mass index and
      heart rate diminished after further adjustments for systolic blood pressure,
      suggesting that the primary effect of body weight is on blood pressure rather
      than on heart rate. CONCLUSION: Our findings indicate that elevated heart rate is
      associated with hypertension and with an atherogenic lipoprotein profile and
      support the suggestion that disturbance of the autonomic nervous system may
      underlie these associations.

PMID- 7621303
TI  - Complementary effects of pravastatin and nicotinic acid in the treatment of
      combined hyperlipidaemia in diabetic and non-diabetic patients.
AB  - BACKGROUND: Given that treatment with a single drug is frequently unsuccessful in
      patients with combined hyperlipidaemia, there is a rationale for the study of
      regimens using drugs that have complementary therapeutic profiles. We therefore
      set out to compare the efficacy of a combined pravastatin and nicotinic acid
      regimen with higher dose monotherapy using either drug in patients with non
      insulin-dependent diabetes and in non-diabetic patients with combined
      hyperlipidaemia. METHODS: Forty-four patients with total-cholesterol levels of
      6.5 mmol/l or higher and triglyceride levels of 2.5 mmol/l or above were randomly
      assigned to receive either pravastatin alone (40mg/day) or nicotinic acid alone
      (1500mg/day) for 12 weeks. At the end of this period, the participants received a
      combination of pravastatin (20mg/day) and nicotinic acid (1000mg/day) for a
      further 12 weeks. The lipid parameters measured included levels of total
      cholesterol, triglycerides, low-density-lipoprotein (LDL) cholesterol and high
      density-lipoprotein (HDL) cholesterol. RESULTS: Thirty-three patients (22 without
      and 11 with diabetes) completed the protocol. Monotherapy with pravastatin was
      more effective than that with nicotinic acid in reducing levels of total
      cholesterol (-24.9 versus -9.8%, P<0.001) and LDL cholesterol (-32.1 versus 
      16.9%, P < 0.01), similar in reducing levels of triglyceride (-28.0 versus 
      31.8%, NS) and tended to be less effective in elevating levels of HDL cholesterol
      (+16.4 versus +30.8%, P = 0.06). Combination therapy was more effective than
      pravastatin monotherapy in reducing levels of triglyceride (-39.3 versus -28.0%,
      P < 0.05) and elevating those of HDL cholesterol (+35.6 versus +16.4%, P < 0.001)
      and was equally effective in reducing total-cholesterol (-22.3 versus -24.9%, NS)
      and LDL-cholesterol (-27.1 versus -32.1%, NS) levels. Combination therapy was
      more effective than nicotinic acid monotherapy in reducing levels of total
      cholesterol (-23.8 versus -9.8%, P < 0.001), triglyceride (-39.4 versus -31.8%, P
      < 0.05) and LDL cholesterol (-35.7 versus -16.9%, P < 0.05) and equally effective
      in elevating HDL-cholesterol levels (+33.6 versus +30.8%, NS). Diabetic and non
      diabetic participants responded similarly to combination therapy. Eleven patients
      (25%) were withdrawn from the study: nine as a result of nicotinic acid
      intolerance (flushing and nausea) and one through pravastatin intolerance
      (nausea); one patient died of a myocardial infarction. Combination therapy
      elevated glycosylated haemoglobin A1c levels in non-diabetic patients (5.5 to
      5.8%, P < 0.001); in diabetic patients, however, the observed rise (7.4 to 7.9%)
      was not statistically significant. Fasting plasma glucose levels, liver function
      tests and levels of creatine kinase or uric acid were unaffected by either
      monotherapy or by combination therapy, with the exception of an elevation of the
      glucose level in diabetic patients receiving nicotinic acid monotherapy.
      CONCLUSION: Pravastatin and nicotinic acid in lower-dose combination are more
      effective than pravastatin alone in reducing levels of triglyceride and elevating
      those of HDL cholesterol and are more effective than nicotinic acid alone in
      reducing total-cholesterol triglyceride and LDL-cholesterol levels. Combination
      therapy is equally effective in type-II diabetic and non-diabetic people. The
      complementary effects of the combination therapy on lipid levels suggest that
      this regimen should be considered as a therapeutic option in patients with
      combined hyperlipidaemia who tolerate the side effects of nicotinic acid.

PMID- 7621304
TI  - Haemostatic factors and lipoprotein (a) in three geographical areas in Finland:
      the Finrisk Haemostasis Study.
AB  - BACKGROUND: An increasing volume of evidence suggests that haemostatic factors
      play a role in the risk of coronary heart disease. It is not known, however,
      whether between-population differences in haemostatic factors correspond with the
      differences in mortality related to coronary heart disease. We examined this
      question in Finland, where, in North Karelia (in the eastern part of the
      country), the mortality from coronary heart disease is 1.5-1.7 times higher than
      that in southwestern areas. METHODS: A random sample of 3000 people aged 45-64
      years was drawn from the population registers of North Karelia, of the area
      surrounding Turku and Loimaa in southwestern Finland and of the Helsinki area in
      southern Finland. Of the 3000 people approached, 79.6% took part in the study.
      differences in coronary heart disease mortality and morbidity. RESULTS: Factor
      VII coagulant activity was significantly higher in North Karelia than in the
      other areas (P = 0.0008). The fibrinogen level was also higher in North Karelia,
      although the difference was significant only among non-smokers (P = 0.02). Levels
      of factor-VII antigen, plasminogen and lipoprotein (a) did not differ between the
      areas. Within North Karelia, the levels of both factor-VII coagulant activity,
      and factor-VII antigen were higher in rural areas than in urban areas. Levels of
      factor-VII coagulant activity, factor-VII antigen and plasminogen were higher in
      women than in men and increased with age in women but not in men. The fibrinogen
      level increased with age in both sexes. CONCLUSION: These baseline findings of
      the Finrisk Haemostasis Study demonstrate that the geographical differences in
      levels of factor-VII coagulant activity and fibrinogen in Finland are consistent
      with the population

PMID- 7621305
TI  - Univalent cation fluxes in human erythrocytes from individuals with low or normal
      sodium intake.
AB  - BACKGROUND: High salt intake is a risk factor for essential hypertension in man.
      There is evidence that, in hypertension, intracellular sodium content and
      univalent cation transport across erythrocyte membranes are changed. It has been
      proposed that a low-sodium diet has an antihypertensive effect; this may be
      related to changes in cation fluxes across plasma membranes. METHODS: Sodium and
      potassium fluxes and the composition of fatty acids were studied in the
      erythrocytes of people who had eaten a low-sodium vegan diet for many years (n =
      9) and in those of controls who had consumed a mixed diet (n = 11) to investigate
      the dependence of these variables on dietary factors. Both systolic and diastolic
      blood pressures were lower in vegans than in controls. RESULTS: The passive
      permeability to sodium (P < 0.05) ,Na+,K+ cotransport (P < .001) and the
      intracellular content of exchangeable sodium (P = 0.076) were decreased in the
      erythrocytes of those who had consumed the low-sodium diet compared with the
      controls. The activity of the Na+-K+ pump, Na+-H+ exchange and the passive
      permeability to potassium were unaltered. Swelling-induced K+,C1- cotransport was
      increased in the erythrocytes of those who had eaten the low-sodium vegan diet
      compared with controls (P < 0.01). The proportion of linoleic acid was increased
      (P < 0.01) at the expense of eicosapentaenoic and docosahexaenoic acids (P <
      0.001) in the erythrocyte membranes of the vegans. CONCLUSION: Our results show
      that levels of intracellular sodium and Na+,K+ cotransport activity, which
      increase in patients with hypertension, decreased in those consuming a low-sodium
      vegan diet. This suggests that the risk of essential hypertension was diminished
      in the vegan participants, confirming our observation that systolic and diastolic
      blood pressures were lower in the strict vegans than in the controls.

PMID- 7621308
TI  - Bibliography of the current world literature.

PMID- 7621309
TI  - Dietary treatment of hyperlipidemia.

PMID- 7621307
TI  - The prediction of coronary heart disease mortality as a function of major risk
      factors in over 30 000 men in the Italian RIFLE pooling Project. A comparison
      with the MRFIT primary screenees. The RIFLE research group.
AB  - BACKGROUND: Few risk functions for the prediction of coronary heart disease
      mortality have been produced in Italy. This study used a large population sample
      to evaluate the effect of major risk factors on coronary mortality. METHODS:
      Coronary deaths in 45 cohorts of men (n = 31317, aged 30-69 years) were studied
      and related to selected cardiovascular risk factors. RESULTS: After 6 years, 1089
      men had died, of whom 239 were coronary fatalities. Univariate and multivariate
      (Cox model) analyses conducted on each age group (30-39, 40-49, 50-59, and 60-69
      years) showed a positive association between coronary deaths and systolic blood
      pressure, serum cholesterol level and cigarette smoking, with few exceptions. A
      multiple logistic model was produced for men aged 35-57 years, assessing the role
      of age, serum cholesterol, cigarettes smoked per day and diastolic instead of
      systolic blood pressure, using the same endpoint as that employed in a similar
      model published from the analysis of MRFIT primary screenees in the USA to
      facilitate valid comparison. The coefficients in the present study were similar
      to those in the US cohort: no statistically significant differences could be
      detected when comparing the pairs of coefficients. CONCLUSION: Coefficients
      relating cholesterol, blood pressure and cigarette smoking to coronary mortality
      in Italian men are similar to those in American men from the same age groups.

PMID- 7621306
TI  - Angiotensin-converting enzyme inhibition in infarct-induced heart failure in
      rats: bradykinin versus angiotensin II.
AB  - BACKGROUND: The beneficial effects of angiotensin-converting enzyme (ACE)
      inhibitors in the prevention of heart failure following myocardial infarction are
      widely accepted. However, the underlying mechanisms are still a matter of
      discussion. We therefore investigated the relative contribution of the breakdown
      of bradykinin and of the inhibition of angiotensin-II synthesis to the beneficial
      actions of ACE inhibitors in chronic heart failure following myocardial
      infarction. METHODS: We compared the effects pretreatment with the ACE inhibitor
      moexipril with those of the type 1 angiotensin (AT1)-receptor antagonist losartan
      on structural and functional cardiac parameters after myocardial infarction in
      rats. In addition, the bradykinin B2-receptor antagonist icatabant was used to
      investigate the role of bradykinin in the cardioprotective effects of ACE
      inhibition. Rats underwent a sham operation or surgery to induce myocardial
      infarction. Treatment was started 1 week before myocardial infarction and
      continued for another 6 weeks after the procedure. RESULTS: Moexipril reduced
      infarct size (100 +/- 9mm2 compared with 165 +/- 8mm2), the ratio of total heart
      weight to body weight (2.6 +/- 0.1 g/kg compared with 2.9 +/- 0.1 g/kg) and end
      diastolic pressure (8.2 +/- 1.5 mmHg compared with 14.0 +/- 1.7 mmHg). All of
      these effects of the ACE inhibitor were blocked by concomitant treatment with
      icatibant. Losartan did not affect any of these cardiac parameters. CONCLUSION:
      The cardioprotective effects of the ACE inhibitor moexipril administered before
      myocardial infarction in the present study were a result of the reduced breakdown
      of kinins rather than of the reduced synthesis of angiotensin II.

PMID- 7621310
TI  - Prognostic stratification after acute myocardial infarction.

PMID- 7621311
TI  - Conventional risk factors reconsidered in patients with acute myocardial
      infarction.
AB  - Large-scale randomized clinical trials have allowed an exploration of the
      interactions between conventional risk factors and prognosis in patients who have
      already suffered acute myocardial infarction. The exposure to risk factors not
      only increases the probability of developing the disease but also affects the
      subsequent prognosis. Elderly, hypertensive and diabetic patients are at
      increased risk both during the in-hospital phase and afterwards. Nevertheless,
      secondary analyses sometimes produce unexpected results; the surprising finding
      of a protective effect of cigarette smoking with respect to death and re
      infarction is probably the best example and illustrates how carefully secondary
      analyses should be performed.

PMID- 7621312
TI  - High- and low-risk groups: early and late prognostic stratification.
AB  - Prognostic data obtained from studies carried out since the advent of
      thrombolysis confirm the notion that short-term survival after acute myocardial
      infarction is primarily influenced by age and clinical indicators of infarct size
      or global left ventricular dysfunction. In survivors of the in-hospital phase of
      infarction, markers of left ventricular failure or dysfunction are still the most
      powerful risk predictors, whereas qualitative variables related to residual
      ischaemia do not predict outcome. The relatively low overall risk profile of
      survivors of the in-hospital phase of infarction in the GISSI-2 study appears to
      reflect favourable changes in the sizes of risk strata that result from a general
      improvement in management strategies.

PMID- 7621313
TI  - The open infarct-related artery theory: a critical view.
AB  - Early reopening of the infarct-related artery salvages myocardium and,
      consequently, preserves left ventricular function, which results in an improved
      survival rate (the early open infarct-related artery theory). Nevertheless, late
      patency of the infarct-related artery is also important, because it prevents
      ventricular remodeling (the late-open infarct-related theory). A comprehensive
      view of the importance of both conditions is presented.

PMID- 7621314
TI  - Cardiac remodeling and failure after myocardial infarction.
AB  - Acute myocardial infarction, particularly when it produces large transmural
      infarcts, can initiate complex changes in the structural and functional
      architecture of both infarcted and non-infarcted regions of the left ventricle,
      known as ventricular remodelling; these changes can profoundly affect left
      ventricular function and, consequently, clinical outcome and prognosis.
      Ventricular remodelling is a dynamic process with regional and global effects on
      wall thickness and composition and on chamber size, shape and function; it can
      include infarct extension, infarct expansion, regional and global distortion and
      ventricular dilatation. A systematic strategy for the [primary] prevention of
      cardiac remodeling should probably be applied as early as possible to all
      patients suffering acute myocardial infarction. A [secondary] prevention strategy
      should focus on the early identification and treatment of subsets of patients
      with evidence of cardiac remodeling, because later treatments have already been
      shown to be beneficial. Cardiologists must choose the strategy most appropriate
      for each individual patient.

PMID- 7621315
TI  - Evidence of residual ischaemia: real danger or myth?
AB  - The extent and severity of residual myocardial ischaemia are well-known as major
      determinants of mortality after myocardial infarction, and non-invasive
      assessment of these parameters still plays a critical role in the management of
      patients. Most of the published data on this topic derive from observations
      collected before the widespread use of thrombolysis. The results of large
      multicentre trials assessing the most appropriate therapies after thrombolysis
      have shown that the more conservative strategy of reserving catheterization and
      revascularization for patients with recurrent spontaneous or induced ischaemia
      may be the best approach. Sophisticated techniques to detect more accurately the
      residual ischaemic burden after infarction have been suggested that would have a
      major impact on clinical decision making and on the cost of health care. The
      relative influence of residual ischaemic on the prognosis after myocardial
      infarction, however, has recently been questioned. The relative risk associated
      with residual ischaemia seems to be low compared with other predictors of
      mortality. The progression of coronary artery disease is variable and highly
      unpredictable, and this may be a major limitation of our ability to predict
      further ischaemic events.

PMID- 7621316
TI  - Arrhythmias and the autonomic nervous system.
AB  - This review discusses the current evidence relating to the prevalence and
      significance of markers of electrical instability and of autonomic dysfunction in
      patients who have suffered acute myocardial infarction in light of recent studies
      performed in patients given thrombolytic therapy during the acute phase. Among
      markers of electrical instability, emphasis is placed upon the frequency of
      ventricular arrhythmias during Holter monitoring, the presence of late potentials
      at signal averaging and the inducibility of ventricular tachycardia during
      programmed electrical stimulation. Among indices of autonomic nervous system
      dysfunction, data relating to heart rate variability and baroreflex sensitivity
      are summarized and discussed.

PMID- 7621317
TI  - Risk factors for atherosclerotic cardiovascular outcomes in different arterial
      territories.
AB  - BACKGROUND: The major cardiovascular risk factors adversely affect all vascular
      territories, increasing the vulnerability to multiple clinical manifestations of
      atherosclerosis. PATIENTS: The population at risk was the Farmingham cohort of
      5209 men and women assessed bienially for the development of overt events of
      coronary heart disease (CHD), congestive heart failure, intermittent
      claudication, and atheroembolic brain infarction. RESULTS: In persons younger
      than 65 years, all the major risk factors were found to impact significantly on
      the incidence of coronary heart disease and intermittent claudication. For stroke
      and cardiac failure, all but the serum cholesterol level were important. In those
      older than 65 years, serum total cholesterol levels and smoking no longer
      influenced the incidence of coronary heart disease. The ratio of total- to high
      density-lipoprotein-cholesterol levels, however, was related to all
      cardiovascular outcomes except stroke at all ages. The impact of cigarette
      smoking on stroke and intermittent claudication persisted in advanced age.
      CONCLUSION: Modification of risk factors for the purpose of preventing a
      particular cardiovascular event should also prevent other outcomes. The impact of
      any particular risk factor on any atherosclerotic cardiovascular disease outcome
      is profoundly influenced by the frequent coexistence of other risk factors. A
      correct appraisal of the hazard and urgency for treatment is best obtained from a
      cardiovascular risk profile estimating the conditional probability of an event
      given the existing constellation of factors.

PMID- 7621318
TI  - Associations between plasma fibrinogen levels and cardiovascular risk factors in
      hypertensive men.
AB  - BACKGROUND: Fibrinogen levels are reported to be elevated in hypertensive
      patients and tend to cluster with nearly all other established cardiovascular
      risk factors. The aim of this study was to evaluate the relationship between
      plasma fibrinogen and a number of other cardiovascular risk factors in patients
      with essential hypertension. METHODS: We studied 118 men with essential
      hypertension, aged 18-65 years. The clinical evaluation included measurements of
      blood pressure (mercury sphygmomanometer, Korotkoff I and V), levels of plasma
      fibrinogen, total cholesterol, high-density-lipoprotein (HDL) cholesterol,
      triglycerides and blood glucose and the ratio of total-cholesterol to HDL
      cholesterol levels; a detailed history of medical and personal habits was also
      recorded. RESULTS: As expected, plasma fibrinogen levels were significantly
      higher in smokers than in non-smokers, with the number of cigarettes smoked
      correlating positively with the fibrinogen level. Patients with a total
      cholesterol level in excess of 220 mg/dl had significantly higher fibrinogen
      levels, and both univariate and multivariate analyses showed total-cholesterol
      and fibrinogen levels to be positively correlated. A weaker but significant
      relationship was noted between the fibrinogen level and triglyceride levels (P =
      0.0017) and between the fibrinogen level and the ratio of total-cholesterol to
      HDL-cholesterol levels (P = 0.0006). Fibrinogen levels were not significantly
      associated with either systolic or diastolic blood pressures. CONCLUSION: A
      family history of hypertension appears to potentiate the tendency of fibrinogen
      to cluster with other cardiovascular risk factors in hypertensive patients.

PMID- 7621320
TI  - Bibliography of the current world literature.

PMID- 7621319
TI  - Ventilatory efficiency is unchanged after physical training in healthy persons
      despite an increase exercise tolerance.
AB  - BACKGROUND: In chronic heart failure, exercise training results in an improvement
      in exercise capacity and a reduction in the ventilatory response to exercise. The
      effects of a physical training programme on the ventilatory response in healthy
      persons is not known. METHODS: Metabolic gas exchange and ventilation were
      measured in 27 young healthy persons aged 31.4 +/- 7.6 years before and after a
      19-week training programme of aerobic exercise; exercise was undertaken three
      times a week for 40 min. Ventilation, the slope of the relationship between
      ventilation and carbon dioxide production (VE-VCO2 slope) and the ventilatory
      equivalent for carbon dioxide were measured using respiratory mass spectroscopy.
      The peak expiratory flow rate in 1 s and forced vital capacity were also
      measured. RESULTS: Mean +/- SEM peak oxygen consumption increased from 39.5 +/-
      1.5 to 45.4 +/- 1.7 ml/kg/min(P<0.001). Exercise time increased from 817 +/- 188
      to 896 +/- 186 s (P<0.001). The respiratory exchange ratio at peak exercise was
      slightly lower after training: 1.30 +/- 0.02 compared with 1.36 +/- 0.03 (P =
      0.02). Ventilation at equivalent stages of exercise was unchanged by training.
      The VE-VCO2 slope did not change (24.52 +/- 0.67 before training, 25.01 +/- 0.80
      after training; NS). There was no change in the ventilatory equivalent for carbon
      dioxide either at rest (38.6 +/- 1.4 compared with 36.2 +/- 1.1; NS) or at its
      lowest point (23.3 +/- 0.6 compared with 22.9 +/- 3.2; NS). Neither exercise
      capacity nor the training response correlated with any of the measured
      ventilatory variables. CONCLUSION: In contrast to the situation in patients with
      chronic heart failure, there is no relationship between ventilatory variables and
      exercise capacity in healthy persons and no change in ventilatory performance as
      a result of physical training.

PMID- 7621321
TI  - Brain noradrenergic systems modulate the ceco-colonic myoelectric activity in
      rats.
AB  - The role of the brain noradrenergic systems in the control of the ceco-colonic
      myoelectric activity was investigated in rats following lesions with
      intracerebroventricular (icv) or intracisternal (ic) injection of 6
      hydroxydopamine (6-OHDA). Controls received the vehicle alone. The ceco-colonic
      myoelectric activity was recorded 3 weeks later in conscious rats chronically
      fitted with electrodes. After icv injection of 6-OHDA, lesions of rostral and
      caudal (spinal) noradrenergic systems were observed whereas only spinal
      noradrenergic systems were lesioned after ic injection. This differential pattern
      of lesions was followed by a differential pattern of ceco-colonic myoelectric
      activity. In fasted animals, a significant increase of the long spike burst (LSB)
      frequency (nb min-1) was observed after icv injection of 6-OHDA whereas no
      modification was observed after ic injection of the neurotoxic. After a 6-g
      pelleted rat diet, a significant increase of the LSB frequency was also observed
      in the icv lesioned group when compared to controls. No modification of the ceco
      colonic noradrenergic innervation was observed, thus confirming the central
      selectivity of these lesions. Lesions of central noradrenergic systems modify the
      LSB frequency in rats; the rostral noradrenergic systems seem to play the major
      role.

PMID- 7621322
TI  - Effects of CCK-receptor antagonist on colonic motor activity in dogs.
AB  - This study employed a cholecystokinin (CCK) antagonist to evaluate whether
      endogenous CCK regulates fasted and fed motor patterns of the colon. Experiments
      were performed in six conscious dogs, each in duplicate. Motor activity was
      recorded by four strain gauge transducers implanted on the colon. The effects of
      the CCK-analogue caerulein and the CCK-antagonist loxiglumide (Rotta, Italy) were
      studied in fasted and fed states. The motor activity was computed for the area
      under contractions. Caerulein given as an intravenous bolus of 50 ng kg-1 during
      a quiescent state caused a burst of phasic and tonic contractions resembling a
      regular non-migrating motor complex. Physiological doses of 10 ng kg-1 caerulein,
      which increases plasma CCK-immunoreactivity to postprandial levels, had no
      effect. Continuous intravenous infusion of 10 mg kg-1 h-1 loxiglumide completely
      abolished the effects of 50 ng kg-1 caerulein. The motor activity stimulated by
      the cholinesterase inhibitor neostigmine (10 micrograms kg-1) was not altered by
      loxiglumide. Loxiglumide given in the fasted state reduced the area under
      contractions in the proximal colon by 26.8 +/- 12.8% compared to the control
      without loxiglumide (P < 0.05). The postprandial increase in motor activity in
      the distal colon, the gastrocolonic response, was significantly inhibited by
      loxiglumide. Moreover, loxiglumide reduced the area under contractions in the fed
      state by 25.4 +/- 10.7% and 19 +/- 7.2% in the proximal and distal colon,
      respectively (P < 0.05). The present results show that loxiglumide acts as a
      specific antagonist of the actions of CCK on colonic motor activity in the
      dog.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7621323
TI  - Vagal control of fasting somatostatin levels.
AB  - The relationship between fasting intestinal motility, plasma concentration of
      somatostatin and vagal integrity was examined in four conscious dogs. Small
      intestinal motility was recorded using subserosally implanted bipolar electrodes.
      The cervical vagosympathetic trunks, previously isolated in skin loops, were
      blocked by cooling. In the fasted state, peaks in somatostatin concentration were
      observed during phase III of the migrating myoelectric complex (MMC). During
      vagal blockade, small intestinal MMCs persisted but with phase II being absent or
      decreased in duration in the duodenum and upper jejunum. Somatostatin levels
      significantly decreased to below the basal levels observed prior to blockade. No
      cycling of somatostatin levels was evident during the period of vagal blockade.
      Upon termination of vagal cooling, normal motility returned and somatostatin
      levels returned to their pre-blockade levels. IN CONCLUSION: (1) plasma
      somatostatin levels cycle with phase III of the MMC in the upper small intestine;
      (2) the cycling of fasting somatostatin concentrations is primarily dependent
      upon intact vagal pathways; and (3) basal plasma somatostatin levels are in part
      vagally dependent.

PMID- 7621325
TI  - Gastrointestinal manometry findings in a case with dilated small bowel and
      disturbed transit treated successfully with bowel plication.
AB  - We report the manometric findings in a case of dilated small bowel and disturbed
      transit successfully treated with plication of the dilated small bowel. The
      female newborn infant required total parenteral nutrition following an operation
      for small bowel atresia. X-ray showed a dilated proximal small bowel. Jejunal
      manometry showed normal phase 3 migration but persistently low-amplitude
      contractions in the dilated segment. After plication of the dilated intestine,
      symptoms of bowel obstruction disappeared. A second manometry two weeks after the
      operation showed contractions with normal amplitude. These findings indicate
      that: (1) disturbed transit in the dilated intestine proximal to small intestinal
      atresia is associated with persistently low contraction amplitude, and (2) the
      amplitude can be increased by the plication of the dilated loop.

PMID- 7621324
TI  - Evidence that enteric motility reflexes can be initiated through entirely
      intrinsic mechanisms in the guinea-pig small intestine.
AB  - Although motility reflexes can be elicited in the intestine in vivo after all
      neural connections with the central nervous system are cut, or in vitro in
      isolated intestinal segments, it is not proven that the cell bodies of the
      primary sensory neurons for these reflexes are in the intestinal wall. It is
      feasible that the nerve cells are in dorsal root ganglia and that axon reflexes
      are involved in the initiation of the reflexes. We have examined reflexes in
      segments of guinea-pig intestine in which extrinsic denervation, 9-11 days before
      the intestine was removed, and isolation of the intestine in vitro were combined.
      The experimental segments were isolated from extrinsic inputs by severing nerves
      in the mesentery and those running in the gut wall that entered the segment. The
      effectiveness of denervation was confirmed histochemically. Ascending and
      descending reflexes were evoked by mucosal distortion or distension and responses
      were recorded by intracellular microelectrodes in the circular muscle. Reflex
      responses recorded after denervation were no different to those recorded from
      control tissue. It is concluded that, in the small intestine of the guinea-pig,
      cell bodies of primary sensory neurons for mucosal and probably for distension
      reflexes are intrinsic to the organ.

PMID- 7621326
TI  - Developmental language impairments: their transactions with other
      neurodevelopmental factors during the adolescent years.

PMID- 7621327
TI  - Assessments of adolescent language.
AB  - I have stressed that language and learning disabilities that are exhibited in the
      preschool or elementary school years often persist into adolescence but that the
      characteristics and implications of these disabilities change with the
      preadolescent and adolescent transitions to metalinguistic maturity. As the
      student with language disabilities matures and as educational demands increase in
      complexity and in level of abstractness, the interactions between language and
      cognition become more apparent. Language disabilities of adolescents are often
      described in relation to observed deficits in the acquisition of content
      (semantics), form (morphology and syntax), and use (pragmatics). I have broadened
      this perspective to consider identification of metalinguistic strengths and/or
      deficits, deficits in the integration and organization of communication,
      reasoning and problem solving, and in conceptualization and creativity. Several
      assessment options were discussed, among them, norm-and criterion- referenced
      testing, language sample analysis, portfolio assessments of integrated
      communication, observational checklists and interviews, classroom language
      probes, and self-assessments. The perspectives taken for assessment have been
      that no single assessment option can satisfy all assessment objectives and/or
      constraints. I have also stressed that all tests are subject to measurement error
      and how to account for this error. Last, but not least, I have shared some of the
      voices of adolescents which express their perspectives and priorities.

PMID- 7621328
TI  - Traumatic brain injury in adolescence: assessment and reintegration.

PMID- 7621329
TI  - Classroom management and instruction for adolescents with language disabilities.

PMID- 7621330
TI  - Developing study, organization, and management strategies for adolescents with
      language disabilities.
AB  - Developing strategies for learning is important for all individuals, but even
      more so for students who have difficulty learning and processing information.
      Because many students with language disabilities have not developed a repertoire
      of such strategies or do not actively apply the strategies they know, direct
      instruction in this area is imperative. It is also important that any strategy
      taught is functional, easily and directly applied to present learning situations,
      and easy to generalize. Determining the variables in a learning situation (the
      script) should provide appropriate choices and direction for strategic teaching
      and learning. The acquisition of strategies involves direct, explicit teaching
      and requires time for modeling, practice, and discussion. Using a cognitive
      strategy model is critical because it supports the later use and generalization
      of strategies, but it is important to explore various models for strategy
      instruction and to work collaboratively with students and teachers. The SLP can
      provide direct instruction, consultation, or training, or can facilitate a
      collaborative model among professionals. In so doing, her impact may reach
      throughout a life, because learning strategies are life strategies, and if
      learned they are tools forever.

PMID- 7621331
TI  - A dynamic interactive developmental view of early speech and language production:
      application to clinical practice in motor speech disorders.

PMID- 7621332
TI  - Clinical evaluation of developmental motor speech disorders.

PMID- 7621333
TI  - Treatment of motor speech disorders in children.

PMID- 7621334
TI  - Augmentative and alternative communication: treatment principles and strategies.
AB  - This article has attempted to clarify the principles of AAC evaluation and
      intervention, in part by dispelling myths that have persisted for too long. To
      the list of general guidelines for deciding when to consider AAC and how to begin
      breaking down the barriers to full participation by children with severe
      impairments, we need to add some warning signs that we have learned to heed in
      our work with these children. These signs are listed in Table 6 and are
      indicators that aspects of an approach to AAC must be altered or the child may
      fail to benefit from an intervention. Each sign conflicts in one way or another
      with current principles of augmentative and alternative communication. We give
      you these signs along with some possible ways to eliminate or prevent these
      errors in the future. Providing the best possible set of strategies for
      communication for a child with severe communication impairments is an enormously
      complex task. Whether a child can or cannot be assessed with standard procedures
      or whether he or she has unitary or multiple disabilities, the barriers to
      communication are many and intricately constructed. Sorting out strategies and
      how to apply them ordinarily requires input from the consumers of AAC (i.e., the
      family, child, and primary communication partners), the core team of
      professionals, as well as a team of specialists in AAC. Conducting evaluations
      and intervention is challenging because of institutional, bureaucratic, and
      professional barriers that each member of the team faces. Few, if any, teams can
      provide services that meet all of the established principles of best practice for
      every child that it serves. Yet, attempts to identify weaknesses within AAC
      programs and work to strengthen them must be given high priority in order to
      provide the best possible AAC services for such children. Only then will it be
      possible for children with severe communication impairments to overcome their own
      barriers and begin to participate in their choice of life's activities. That is,
      after all, the ultimate goal.

PMID- 7621335
TI  - Team management for young children with motor speech disorders.

PMID- 7621336
TI  - Speech motor development.

PMID- 7621338
TI  - Increased bone resorption and decreased bone formation in Chinese patients with
      hip fracture.
AB  - Biochemical markers of bone formation (bone-specific alkaline phosphatase and
      osteocalcin) and bone resorption (hydroxyproline excretion and bone isoenzyme of
      acid phosphatase) were measured in 30 patients (15 M and 15 F) with hip fracture
      and 30 healthy subjects matched for age and sex. Bone isoenzyme of tartrate
      resistant acid phosphatase (TRACP) was measured by a recently developed specific
      immunoassay. Serum osteocalcin concentration and bone-specific alkaline
      phosphatase activity were significantly lower and serum TRACP concentration and
      urinary hydroxyproline excretion were elevated in patients compared with healthy
      subjects. We suggest that there is reduced bone formation and increased bone
      resorption in patients with hip fracture.

PMID- 7621337
TI  - Androgens and bone.
AB  - Androgen receptors are present at low densities in osteoblasts. Androgens are
      also metabolized in bone. (Non)aromatizable androgens probably induce
      proliferation of osteoblasts and differentiation. A direct effect of androgens on
      osteoclasts has not been demonstrated. Androgens may however inhibit bone
      resorption indirectly, by an inhibition of the recruitment of osteoclast
      precursors from bone marrow, by decreased secretion of interleukin-6 and/or
      prostaglandin E2, and/or by an increased sensitivity of marrow cells or
      osteoblasts for bone resorption stimulating factors such as PTH. The recent
      demonstration of androgen receptors in bone marrow stromal and osteoclast-like
      cells opens new perspectives in this respect. During puberty, androgens stimulate
      bone growth both directly and indirectly. Observations in androgen-resistant
      animals clearly demonstrated that the sexual dimorphism of bone depends on the
      presence of a functional androgen receptor. Optimal peak bone mass seems related
      to an appropriately timed androgen secretion. In adults, androgens are also
      involved in maintenance of the male skeleton. Androgen replacement may prevent
      further bone loss in hypogonadal men, however, it seems difficult to fully
      correct bone mass in these men.

PMID- 7621339
TI  - Dual-energy X-ray absorptiometry at the lumbar spine in German men and women: a
      cross-sectional study.
AB  - A cross-sectional, population-based study of 238 randomly selected females and
      224 males with German ethnic background (aged 20-80 years) was carried out to
      establish lumbar spine bone mineral density (BMD) values, using dual X-ray
      absorptiometry (DXA), for a German population. Comparison was made to the
      reference range provided by the manufacturer of the DXA equipment. No sex
      difference in peak spine BMD was found in our study (1.091 +/- 0.114 g/cm2 for
      males versus 1.070 +/- 0.113 g/cm2 for females, n.s.). Different patterns of bone
      loss could be detected in both sexes. In premenopausal women there was no
      significant correlation between age and BMD (y = 1.044 + 0.00047x, r = 0.03, P =
      0.73) whereas reduction of female BMD at the spine was demonstrated in
      postmenopausal women (y = 1.189-0.0041x, r = -0.28, P = 0.01), underscoring the
      important role of the menopause for later manifestation of spinal osteoporosis in
      women. In contrast, in males we found no significant change of BMD with aging (y
      = 1.071-0.0007x, r = -0.08, P = 0.25). Employing commonly used exclusion
      criteria, BMD values of the study subjects were found mostly within the normal
      range of BMD. The major finding of our study was good concordance between female
      data of our study population and the reference data provided by the manufacturer.
      Clinically significant discrepancies between our data and the Hologic reference
      range for males could be detected. Our data on males (30-39 years of age) were up
      to 7% lower than those provided by the manufacturer, probably due to differences
      in sampling procedures.

PMID- 7621340
TI  - Bone density in medieval skeletons.
AB  - We studied the most complete skeletons found in an excavation from the 14th and
      15th century in central Stockholm. One hundred eighty-seven were from men and 156
      from women: 241 individuals were estimated to be between 20 and 39 and 102
      between 40 and 59 years old at death. We examined the bones radiographically and
      by dual photon absorptiometry. The bone mineral density (BMD) was similar to the
      finding in North America and Northern Europe today as was the relationship
      between men and women. However, there appeared to be a higher diaphyseal bone
      density in the lower extremities, especially in men. The femur score was higher
      and the BMD of the femoral and tibial shafts was higher than today. In the upper
      extremities the diaphyseal bone density was lower. Meema's index, as well as the
      metacarpal score, was smaller than in individuals in this century and the BMD of
      the humeral shaft was also lower than seen today. Overall, the metaphyseal bone
      density was similar to what we now consider normal; i.e., the mean BMD of the
      femoral neck was 0.96 g/cm2 in men and 0.90 g/cm2 in women and of the distal
      radius 0.43 and 0.32 g/cm2, respectively. The low diaphyseal density and in the
      upper extremities may be related to the nutritional status, whereas the greater
      need for walking and standing in the 14th and 15th century might have led to the
      high diaphyseal density in the lower extremities. There was no evidence of bone
      loss after 40 years of age in either sex in our study. The average expected
      lifespan for an adult individual was less than 50 years and we suggest that the
      relatively high bone density in the older age group may be due to selection of
      the most physically fit. The activity pattern, therefore, may be considered the
      most important determinant for the differences.

PMID- 7621341
TI  - Bone histomorphometry in men with spinal osteoporosis.
AB  - The purpose of this investigation was to determine whether there is an effect of
      age and the presence of predisposing risk factors on the pattern of bone
      resorption in men with spinal osteoporosis. We present iliac bone
      histomorphometric data after in vivo double tetracycline labeling in 21 men aged
      34-74 with significant spinal osteoporosis as evidenced by compression spinal
      fracture without significant trauma. Fourteen of the 21 men (67%) had
      identifiable predisposing risk factors for their osteoporosis, such as ethanol
      abuse, hypercortisolism, hypogonadism, or underlying medical conditions. The
      other 7 men (33%) had no such identifiable risk factors. The conclusions of the
      study were that (1) there was no correlation between age of the patient and
      degree of bone resorption based on two parameters of resorption and (2) there was
      no difference in the pattern of bone resorption between the groups with and
      without known predisposing risk factors for osteoporosis or underlying medical
      conditions.

PMID- 7621342
TI  - An 18-year prospective study of dietary calcium and bone mineral density in the
      hip.
AB  - The object of this study was to determine whether a single 24-hour diet recall of
      calcium intake obtained an average of 18 years previously would predict bone
      mineral density (BMD) in the hip in older men and women. A prospective population
      based cohort study was done in Rancho Bernardo, California. Between 1973 and
      1975, a 24-hour diet recall was obtained in 140 men and 220 women aged 45 and
      older by a trained interviewer using food models and containers. Responses were
      coded by the Nutrition Coordinating Center, University of Minnesota. Between 1988
      and 1991, BMD in the femoral neck, trochanter, and intertrochanter was measured
      using dual-energy x-ray absorptiometry. Results showed that age-adjusted mean BMD
      levels increased significantly with increasing tertile of calcium intake at all
      hip sites in women, with the most striking difference at the femoral neck. These
      associations persisted after adjustment for body mass index, smoking, exercise,
      alcohol intake, use of estrogen replacement therapy, and number of years
      postmenopausal. No significant trends were seen for men at any hip site. It is
      concluded that low dietary calcium predicts low BMD in older women independent of
      other major determinants of BMD.

PMID- 7621343
TI  - Ultrasound bone measurement in pediatric subjects.
AB  - Ultrasound bone measurement in healthy (n = 71) and osteopenic (n = 18) children
      aged 6 through 13 years of both sexes has been evaluated using the Achilles
      densitometer (Lunar Corporation). Measurements on the os calcis included speed of
      sound (SOS), broadband ultrasound attenuation (BUA), and a calculated "stiffness"
      index. The Achilles was adapted for children by a special positioning procedure
      that included the use of foot shims, and beam collimation on the receiving
      transducer. The precision of ultrasound results was comparable to that in adults
      (0.2% for SOS, 1.5% for BUA, and 1.8% for stiffness). SOS, BUA, and stiffness
      values increased with age in both sexes. Ultrasound measurements were correlated
      with bone mineral density (BMD in g/cm2) of the heel, AP spine (L2-L4), and total
      body by dual X-ray absorptiometry (DXA) densitometry (Lunar DPX-L). SOS, BUA, and
      stiffness measurements were significantly lower in osteopenic children (Z
      approximately -1.9 to -2.5) (P < 0.0001) than in normal age-matched controls.
      Total body BMD showed a higher Z-score than stiffness (-3.3 versus -2.5), but
      stiffness showed a greater percentage decrease (-30% versus -18%). In conclusion,
      ultrasound measurements of bone in children provide both good precision and
      discrimination of normals from osteopenic patients.

PMID- 7621344
TI  - Regulation of renal calbindin-D28K: the role of calcitonin.
AB  - Infusion of calcitonin lowers circulating calcium, but in the distal tubule of
      the kidney, pharmacological doses of calcitonin increase the active calcium
      reabsorption. Calbindin-D28k plays a significant role in the calcium reabsorption
      in the distal convoluted tubule of the kidney. The effect of calcitonin on renal
      calbindin-D28k in relation to calcium metabolic changes was therefore examined.
      In study 1, thyroparathyroidectomy followed by autotransplantation of the
      parathyroid glands (TX) was compared with a sham operation in rats. TX reduced
      plasma calcitonin from 54 +/- 2 to 9 +/- 1 pg/ml (P < 0.001), whereas ionized
      calcium and parathyroid hormone were returned to the control value after an
      initial decrease, indicating a successful implantation of the parathyroid glands.
      No changes were seen in calbindin-D or plasma 1,25(OH)2D. In study 2,
      subcutaneous infusion of salmon calcitonin 2.5 U/kg/hour via osmotic pumps was
      compared with infusion of vehicle in rats. Ionized calcium was reduced from 1.37
      +/- 0.01 to 1.33 +/- 0.02 mmol/liter (P < 0.05), whereas no changes were seen in
      renal or intestinal calbindin-D or in plasma 1,25(OH)2D. After TX, only
      calcitonin decreased whereas the other calcium metabolic parameters showed no
      change. This indicates that in rats, selective elimination of calcitonin does not
      influence other parameters of the calcium metabolism and that the effect of
      calcitonin on calcium transport in the distal tubule is not mediated via an
      increase in renal calbindin-D28k.

PMID- 7621345
TI  - Porcine osteochondrosis: deficiencies in transforming growth factor-beta and
      insulin-like growth factor-I.
AB  - Osteochondrosis and dyschondroplasia are common multifocal disturbances of
      endochondral ossification in many species of domestic animals, and are
      characterized by the retention of avascular cartilage. These cartilage disorders
      are characterized by a failure of chondrocyte differentiation, matrix
      mineralisation and its replacement by bone. Rabbit polyclonal antibodies to
      transforming growth factor-beta (TGF-beta) and to insulin-like growth factor-I
      (IGF-I) were used to detect the two growth factors in normal and osteochondrotic
      porcine epiphyses. In the normal pig epiphyses IGF-I and TGF-beta were present in
      the chondrocytes of the epiphyseal hyaline cartilage and IGF-I was readily
      localised to the hypertrophic chondrocytes in the growth cartilage adjacent to
      the epiphyseal ossification centre. Both growth factors were found to be
      deficient in chondrocytes at sites of osteochondrosis. Both these growth factors
      are thought to be involved in the cascade of events associated with chondrocyte
      function during endochondral ossification. Deficiencies in TGF-beta and IGF-I
      demonstrated in porcine osteochondrosis and previously shown in avian
      dyschondroplasia suggest further similarities in the pathogenesis of these
      conditions.

PMID- 7621346
TI  - Volumes of chick and rat osteoclasts cultured on glass.
AB  - We have examined the relationship between the number of nuclei of an osteoclast
      and its volume. Chick and rat cells were released from long bones by chopping the
      shafts and flushing the fragments in Eagle's Minimum Essential Medium with added
      10% fetal calf serum. The bone cell suspension was seeded onto glass coverslips.
      In Experiment 1, rat and chick cells were allowed to settle for 15 minutes, more
      medium was then added, and the cells were cultured in 5% CO2 at 37 degrees C for
      4 hours. In Experiment 2, only rat cells were used, and the cells were cultured
      in the presence or absence of 10(-6) M 3-amino-1-hydroxypropylidene-1,1
      bisphosphonate (APD) in the medium for 4 or 6 hours. The coverslips were washed
      in 37 degrees C phosphate-buffered saline and fixed for 24 hours in 2.5%
      glutaraldehyde in isotonic cacodylate buffer (initially 37 degrees C). The chick
      cells were critical point dried (CPD) or freeze dried (FD); all rat cells were
      FD. After drying, cells were coated with gold by vacuum evaporation. The volumes
      and areas of osteoclasts were measured using a video-rate, line-confocal
      reflection laser scanning microscope and the number of nuclei in each cell was
      counted. The volumes and volumes per nucleus of the FD cells were larger than
      those of the CPD cells but there was no significant difference in plan-areas. Rat
      osteoclasts were larger than chick cells in all the measured parameters except
      the mean number of nuclei/cell. The correlation coefficients for the areas,
      volumes, and the numbers of nuclei for rat and chick cells were all high (r >
      0.725). The volumes and volumes per nucleus, but not the areas or areas per
      nucleus, of the osteoclasts cultured with APD were significantly smaller than
      control cells. We conclude that FD causes less shrinkage than CPD; chick
      osteoclasts are about two-thirds the size of rat osteoclasts; and 10(-6) M APD
      caused a reduction of rat osteoclast volume and volume per nucleus of 21%.

PMID- 7621348
TI  - EDTA-insoluble, calcium-binding proteoglycan in bovine bone.
AB  - A calcium ion precipitable, trypsin-generated proteoglycan fragment has been
      isolated from the demineralized, EDTA-insoluble matrices of bone. The
      demineralized matrix was completely digested with trypsin, increasing
      concentrations of CaCl2 were added to the supernatant, and the resulting
      precipitates were analyzed. The amount of precipitate gradually increased with
      higher concentrations of calcium and was reversibly solubilized by EDTA. After
      molecular sieve and anion exchange chromatography, a proteoglycan-containing peak
      was obtained. Immunochemical analysis showed that this peak contained chondroitin
      4-sulfate and possibly keratan sulfate. Amino acid analysis showed that this
      proteoglycan contained high amounts of aspartic acid/asparagine (Asx), serine
      (Ser), glutamic acid/glutamine (Glx), proline (Pro), and glycine (Gly); however,
      it contained little leucine (Leu) which suggests that it is not a member of the
      leucine-rich small proteoglycan family. In addition, significant amounts of
      phosphoserine (P-Ser) and hydroxyproline (Hyp) were identified in hydrolysates of
      this fraction. A single band (M(r) 59 kDa) was obtained on SDS-PAGE that stained
      with Stains-all but not with Coomassie Brilliant Blue R-250. If bone powder was
      trypsinized prior to demineralization, this proteoglycan-containing fraction was
      not liberated. Collectively, these results indicate that a proteoglycan occurs in
      the demineralized matrix that is precipitated with CaCl2 and is closely
      associated with both mineral and collagen matrices. Such a molecule might
      facilitate the structural network for the induction of mineralization in bone.

PMID- 7621347
TI  - Phenytoin and fluoride act in concert to stimulate bone formation and to increase
      bone volume in adult male rats.
AB  - We have recently demonstrated that phenytoin is an osteogenic agent at low doses.
      The present paper describes observations that a mitogenic dose (i.e., 20 microM
      in BGJb medium) of fluoride significantly augments the phenytoin-dependent
      stimulation of normal human bone cell proliferation and alkaline phosphatase
      (ALP) activity in cell culture. Additionally, the present study was designed to
      investigate whether fluoride and phenytoin would interact to increase bone
      formation in rats in vivo. Four groups of weight-matched adult male rats received
      daily I.P. injection of (1) vehicle (10% DMSO), (2) 5 mg/kg/day phenytoin, (3) 5
      mg/kg/day phenytoin and 50 ppm NaF, and (4) 50 ppm NaF and vehicle, respectively,
      for 36 days. Sodium fluoride (NaF) was delivered in drinking water. Blood samples
      were drawn weekly and analyzed for serum osteocalcin, ALP, calcium, phosphorus,
      and 25(OH)D3. Rats were labeled with tetracycline at day 21 and 30 and
      histomorphometric analysis was carried out on the tibia at the end of the
      experiment. Neither agent by itself or together affected the serum calcium,
      phosphorus, or 25(OH)D3 levels. All measures of bone formation, i.e., serum
      osteocalcin level and ALP activity, bone ALP specific activity, mineral
      apposition rate, bone formation rate, and % bone formation surface, were
      increased by each agent. Fluoride and phenytoin together produced bigger
      increases in each parameter than did each agent alone. Trabecular bone volume was
      increased in the tibial metaphysis by fluoride or phenytoin alone; and when
      administered together, the two agents produced a greater increase.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7621349
TI  - Stimulation by bone sialoprotein of calcification in osteoblast-like MC3T3-E1
      cells.
AB  - Bone sialoprotein (BSP) containing an Arg-Gly-Asp cell-binding sequence was
      purified from bovine bone 4 M guanidine-HCl extract after HCl demineralization by
      a series of chromatographic procedures. When this protein was coated on culture
      dishes in the presence of type I collagen, it increased both DNA content and
      alkaline phosphatase (ALP) activity in osteoblast-like MC3T3-E1 cells, and
      stimulated calcification in the cells, whereas fibronectin, another cell-binding
      protein, showed a marked increase in the DNA content but had little effect on the
      ALP activity. These findings suggest that BSP is mitogenic for preosteoblasts and
      differentiating the cells into osteoblasts, thereby stimulating bone
      calcification.

PMID- 7621350
TI  - Barbiturate and bone resorption.

PMID- 7621351
TI  - Appendicular cortical bone loss after age 65: sex-dependent event?
AB  - Distal radius photodensitometric and second metacarpal radiogrammetric
      measurements were obtained from computerized analyses of standard hand X-Ray
      films of 296 Caucasian subjects (189 women and 107 men). This sample included 134
      subjects > or = 65 years old (75 women and 59 men). Distal radius bone density
      and metacarpal index showed a significant linear decrease with age in both sexes.
      Rates of bone loss, calculated from the regression curves, were -0.7% per year in
      women and -0.5% per year in men by distal radial photodensitometry, and -0.49%
      per year in women and -0.33% per year in men by metacarpal radiogrammetry. In the
      elderly subgroup, women > or = 65 years of age showed an even faster bone loss,
      with an annual decrease of -1.4% by distal radial photodensitometry. Conversely,
      men > or = 65 years of age had no significant bone loss, not even by metacarpal
      radiogrammetry. In conclusion, these data suggest that appendicular cortical bone
      loss occurs at a higher rate in elderly females than in the elderly males, both
      at the distal radial and at the metacarpal site.

PMID- 7621352
TI  - On fluoride and bone strength.

PMID- 7621353
TI  - Species differences in the physical and transport properties of airway
      secretions.
AB  - The clearance of airway secretions is vital in protecting the mammalian lung from
      pollution and infection. Diverse animal models have been used to study lung
      diseases associated with impaired secretion clearance. The extrapolation of data
      from animal models to humans is based on the assumption that there are structural
      and functional similarities in the airway epithelium and secretions. This
      manuscript reviews regulation of mucus secretion as well as the physical and
      transport properties of respiratory mucus. As tracheal size increases, the
      rigidity of airway secretions decreases, and rigidity is inversely correlated
      with mucociliary transportability. These differences are placed in the context of
      previously reported species and regional differences in transepithelial potential
      difference and the tracheobronchial epithelial cell population. Tracheal mucus
      transport velocity varies with the species studied and has been shown to
      positively correlate with tracheal surface area. A progressive increase in the
      rate of mucus transport from the small to the large airways has also been
      reported. The reduction in mucus rigidity from small to large airways could be
      one of the mechanisms responsible for velocity gradients, which facilitate
      mucociliary transport. Because airway dimensions, rather than anatomic level of
      the airway, may better predict epithelial secretory response, studies to assess
      the physiologic responses in human airways require the use of an animal model
      with a similar-sized airway.

PMID- 7621355
TI  - The epithelial barrier and airway responsiveness.
AB  - Epithelial injury and bronchial hyperresponsiveness are commonly associated with
      airway disease, and are widely considered to occur as the result of inflammatory
      changes in the airway wall. Mechanistically, the airway epithelium may influence
      the sensitivity of the airways to provocative stimuli through its primary
      function as a cellular barrier between the air and the interstitium, or by
      liberating a variety of bronchoactive mediators, e.g., lipoxygenase and
      cyclooxygenase products, nitric oxide, and an epithelium-derived relaxing factor
      (EpDIF). Much attention has focused on the latter function of the epithelium,
      particularly the putative EpDIF, which has an action considered to be analogous
      to that of endothelium-derived relaxing factor in blood vessels. The modulation
      of airway calibre by the epithelium has recently been investigated in vitro using
      tubular preparations of bronchi, where removal of, or damage to, the epithelium
      increases the sensitivity to agonists by several orders of magnitude. This
      contrasts with the effect of removing the epithelium on strips or rings of airway
      wall, where the increase in sensitivity is small and rather variable, but this
      has been the primary observation for proposing a putative EpDIF. This review
      evaluates the barrier or protective function of the airway epithelium and the
      major role it plays in the modulation of airway responsiveness. A role of a
      putative EpDIF seems, at best, to be of minor functional significance.

PMID- 7621354
TI  - Functional and molecular aspects of prostaglandin E receptors in the cortical
      collecting duct.
AB  - Endogenous prostaglandin (PG) E2 production potently modulates salt and water
      transport in the kidney. Multiple direct effects of PGE2 on epithelial water and
      sodium transport have been demonstrated in the rabbit cortical collecting duct
      (CCD). Both functional and molecular studies now suggest that these disparate
      effects of PGE2 on CCD function are mediated by different EP receptors. When
      added in the presence of vasopressin, PGE2 inhibits cyclic AMP generation and
      water absorption. These effects are mediated via an inhibitory G-protein (Gi). In
      situ hybridization demonstrates high levels of expression of the Gi-coupled EP3
      receptor in the rabbit collecting duct. However, by itself, PGE2 also stimulates
      cyclic AMP generation and water permeability. These effects appear to be mediated
      via a distinct EP receptor (possibly an EP4 receptor). PGE2 also increases
      intracellular Ca2+ in the CCD and inhibits Na+ absorption via a Ca(2+)-dependent
      mechanism. The EP1 receptor is postulated to be responsible for this action of
      PGE2. We suggest receptor-selective prostaglandin analogs may be used to
      selectively modulate sodium and water transport in the kidney.

PMID- 7621356
TI  - Pharmacology of montelukast sodium (Singulair), a potent and selective
      leukotriene D4 receptor antagonist.
AB  - Montelukast sodium (Singulair), also known as MK-0476 (1-(((1(R)-(3-(2-(7-chloro
      2-quinolinyl)-(E)-ethenyl)phenyl)(3-2-(1- hydroxy-1
      methylethyl)phenyl)propyl)thio)methyl)cyclopropane) acetic acid sodium salt, is a
      potent and selective inhibitor of [3H]leukotriene D4 specific binding in guinea
      pig lung (Ki 0.18 +/- 0.03 nM), sheep lung (Ki 4 nM), and dimethylsulfoxide
      differentiated U937 cell plasma membrane preparations (Ki 0.52 +/- 0.23 nM), but
      it was essentially inactive versus [3H]leukotriene C4 specific binding in
      dimethylsulfoxide-differentiated U937 cell membranes (IC50 10 microM) and
      [3H]leukotriene B4 specific binding in THP-1 cell membranes (IC50 40 microM).
      Montelukast also inhibited specific binding of [3H]leukotriene D4 to guinea pig
      lung in the presence of human serum albumin, human plasma, and squirrel monkey
      plasma with Ki values of 0.21 +/- 0.08, 0.19 +/- 0.02, and 0.26 +/- 0.02 nM,
      respectively. Functionally, montelukast antagonized contractions of guinea pig
      trachea induced by leukotriene D4 (pA2 value 9.3; slope 0.8). In contrast,
      montelukast (16 microM) failed to antagonize contractions of guinea pig trachea
      induced by leukotriene C4 (45 mM serine-borate), serotonin, acetylcholine,
      histamine, prostaglandin D2, or U-44069. Intravenous montelukast antagonized
      bronchoconstriction induced in anesthetized guinea pigs by i.v. leukotriene D4
      but did not block bronchoconstriction to arachidonic acid, histamine, serotonin,
      or acetylcholine. Oral administration of montelukast blocked leukotriene D4
      induced bronchoconstriction in conscious squirrel monkeys, ovalbumin-induced
      bronchoconstriction in conscious sensitized rats (ED50 0.03 +/- 0.001 mg/kg; 4 h
      pretreatment), and also ascaris-induced early and late phase bronchoconstriction
      in conscious squirrel monkeys (0.03-0.1 mg/kg; 4 h pretreatment). A continuous
      i.v. infusion of montelukast (8 micrograms.kg-1.min-1) resulted in a 70% decrease
      in the peak early response and a 75% reduction of the late response to ascaris
      aerosol in allergic conscious sheep. Montelukast, a potent and selective
      leukotriene D4 receptor antagonist with excellent in vivo activity is currently
      in clinical development for the treatment of asthma and related diseases.

PMID- 7621358
TI  - Synthesis and biological activity of histogranin and related peptides.
AB  - Histogranin (HN) was first isolated from bovine adrenal medulla and shown to be a
      pentadecapeptide displaying N-methyl-D-aspartate (NMDA) receptor antagonist
      activity. To determine the active pharmacophore of HN, fragments of the peptide
      were synthesized and their structure-activity relationships studied by measuring
      their ability to displace the binding of [125I][Ser1]HN to rat brain membrane
      preparations and to block NMDA-induced convulsions in mice. In the binding assay,
      only the full length peptide HN and HN(1-10) displayed a high affinity (Ki of 72
      and 162 nM, respectively). All other tested fragments with deletions at the N-
      and (or) C-terminals of the molecule showed large (16- to 2500-fold) decreases in
      potency. The least active peptide fragment tested was HN(6-10) (Ki of 164
      microM). In vivo, HN and HN(2-15) (100 nmol; i.c.v.) produced 94 and 40%
      protection against NMDA-induced convulsions in mice, respectively. None of the
      other peptide fragments displayed significant anticonvulsant activity. The
      protective activity of HN (60 and 100 nmol) was markedly antagonized by
      coadministration of HN(1-10) (100 nmol). The results indicate that the in vivo
      anti-NMDA and in vitro binding activities of HN and related peptides, with the
      exception of HN(1-10), depend upon the integrity of the molecule. On the other
      hand, the high affinity of HN(1-10) for HN binding sites correlates well with its
      antagonist effects towards the activity of the parent peptide.

PMID- 7621357
TI  - Effects of intravenous infusions of noradrenaline into the pregnant ewe on
      uterine blood flow, fetal renal function, and lung liquid flow.
AB  - To determine the effects on the fetus of high maternal levels of noradrenaline,
      experiments were carried out in 17 pregnant ewes (123-137 days gestation).
      Intravenous infusion of 40 mg/min of norepinephrine to the ewe for 1.5 h
      increased maternal arterial pressure and significantly decreased maternal
      placental blood flow (p < 0.05). Fetal arterial pressure did not change, but
      fetal arterial PO2 fell (p < 0.01) and PCO2 rose (p < 0.01). Fetal urine flow
      fell and osmolality rose (p < 0.01), fetal lung liquid flow and osmolar excretion
      fell (p < 0.01, p < 0.05, respectively), and the lung sodium:potassium ratio
      changed. These effects of high levels of maternal noradrenaline were transient,
      i.e., 2.5 h after the infusion of noradrenaline had finished, fetal urine flow
      and lung liquid flow had both returned to control values and fetal PCO2 was
      significantly depressed relative to control values (p < 0.01). It is concluded
      that high levels of maternal catecholamines reduce placental blood flow and cause
      small changes in fetal oxygenation. These changes are sufficient to transiently
      affect fetal water excretion and to reduce lung liquid flow.

PMID- 7621359
TI  - Deafferentation and the Role of Sensory Afferents in Human Motor Control.
      Conference proceedings. Quebec, Canada, May 14-15, 1993.

PMID- 7621360
TI  - Reorganisation in human motor cortex.
AB  - Transcranial magnetic stimulation over the motor cortex was used to construct a
      map of the effective sites on the scalp from which short-latency electromyogram
      responses could be evoked in muscles proximal to either an amputation stump (two
      subjects) or an ischemically anesthetized forearm (two subjects). At rest, the
      maps were larger and the responses bigger when stimulating contralateral to the
      amputated arm or after anesthesia than they were in the intact arm or before
      anesthesia. However, this difference disappeared when the maps were constructed
      during a small tonic voluntary contraction of the target muscle. We conclude that
      reorganisation of the corticospinal projection to a muscle at rest may no longer
      be present during activity. If so, this calls into question the possible
      functional benefits of such reorganisation in the control of movement after
      peripheral damage.

PMID- 7621361
TI  - Sense of muscular effort and somesthetic afferent information in humans.
AB  - Laboratory and clinical observations of patients with a large-fiber somatic
      sensory neuropathy indicate a dramatic inability of these patients to set
      accurate tonic or phasic levels of muscle activity needed to maintain static
      postures and to reproduce simple movements. These observations suggest that
      somatic sensation contributes to sensations of motor output, previously thought
      to be mediated by central mechanisms of corollary discharge. We review data
      describing psychophysical performance on weight-matching tasks and discuss new
      experiments on reaching tasks done by patients with a large-fiber sensory
      neuropathy and normal controls. In combination, the data show that patients with
      peripheral sensory deficits exhibit an impaired sense of muscular effort and the
      consequences of active movement. In addition, the data on weight matching
      indicate that the basis of disrupted effort sense relates to an inability to
      correlate psychophysical decisions with concomitant muscle activity. In new
      experiments, accuracy to match actively achieved arm end points by pointing was
      decreased in patients with large-fiber sensory neuropathy. The collective results
      suggest that appreciation of motor output is mediated in part by peripheral
      return from somatic sensory afferent systems.

PMID- 7621362
TI  - Evoked potentials in a subject with a large-fibre sensory neuropathy below the
      neck.
AB  - The results from experiments in various modalities of evoked potentials are
      described in a subject with a complete large peripheral neuropathy below the
      neck. He has no tactile or position sensitivity below that level, but has
      retained fatigue, pain, and temperature sensation. Percutaneous electrical
      stimulation of peripheral nerves led to scalp recorded evoked potentials with
      thresholds and propagation velocities compatible with conduction along A-delta
      peripheral pathways. CO2 laser evoked potentials were similar to those seen in
      controls, further support for intact A-delta peripheral fibres. Movement-related
      cortical potentials (MRCPs) were recorded associated with active and passive
      movement of the middle finger. The former were normal, evidence that the
      termination of the MRCP is not dependent on peripheral feedback. By comparing
      passive MRCPs between controls and the subject it was possible to establish which
      parts of the potentials are visual and which are proprioceptive and to gain
      evidence of central reorganisation in the subject. Magnetic brain stimulation was
      used to show that the subject did not perceive induced movement, had a normal
      centrally originating silent period, and could focus his attention during real
      and imagined movement of the finger more successfully than could normal controls.

PMID- 7621363
TI  - Contribution of proprioception for calibrating and updating the motor space.
AB  - The absence of muscular proprioception, whether at a segmental or at a central
      level, impairs performance in several ways. The contribution of proprioception to
      movement control and learning is not easily dissociated from that of other
      sources of sensory information (e.g., vision). Therefore, the rare clinical cases
      of extensive neuropathy, depriving the brain massively and permanently of its
      presumed main sources of dynamogenic information from skin and muscles, are of
      very special interest. Two such patients and controls were tested in experiments
      investigating (i) force production, (ii) amplitude coding, (iii) spatial
      reference frames in pointing, and (iv) prismatic adaptation. Overall, our results
      highlight the key role of proprioceptive afferents for calibrating the spatial
      motor frame of reference, and the powerful substitutive properties of the central
      nervous system.

PMID- 7621364
TI  - Is proprioception important for the timing of motor activities?
AB  - This study tested whether a deafferented patient demonstrates impaired timing
      ability compared with four control subjects. By comparing normal subjects with
      the deafferented patient, some insight was expected on the importance of
      proprioception in timing of motor behavior. The protocol was set to enhance the
      strategy of the subjects in using feedbacks. Subjects had to synchronize finger
      taps with a sound produced at regular intervals. Once synchronized, the bips were
      muted and the subjects had to continue the tapping at the same pace.
      Interresponse interval (IRI) variability was measured under two feedback
      conditions: with and without vision and auditory feedback. The Wing and
      Kristofferson model (A.M. Wing and A.B. Kristofferson. Percept. Psychophys.
      13(3): 455-460, 1973) was used to segment IRI variance into separate components:
      a central clock and a peripheral motor delay. When the deafferented patient saw
      and heard the outcome of her tapping movements, there was a greater variability
      in successive intervals between taps than when vison and hearing were blocked. We
      interpret this variability as indicating that the subject used auditory and
      visual feedback to maintain a correct overall rhythm. The patient may easily
      substitute visual and (or) auditory feedback for her defective proprioception for
      movement timing. However, this substitution proved to be inefficient in the
      limited training period provided in this experiment. The results suggest that the
      proprioceptive contribution to the time-keeping mechanism presumably depends on
      the presence of an efference copy signal.

PMID- 7621365
TI  - Representation of hand position prior to movement and motor variability.
AB  - Pointing accuracy of six human subjects was measured in two blocked conditions
      where the hand was either never visible (T: target only) or only visible in
      static position prior to movement onset (H+T: hand+target). It was shown in
      condition H+T that, viewing the hand prior to movement greatly decreased end
      point variability compared with condition T. This effect was associated with a
      significant modification of the movement kinematics: the H+T condition induced a
      shortened acceleration phase with a corresponding lengthened deceleration phase,
      compared with the T condition. These results led us to the hypothesis that
      viewing the hand prior to movement onset allowed a decrease of pointing
      variability through a feedback process. This hypothesis was further tested by
      turning the target off during the deceleration phase of the movement at half peak
      velocity. It was shown that turning the target off had no effect upon the T
      condition but induced a significant increase of pointing variability in the H+T
      condition. This result suggests that vision of the static hand enhances the
      proprioceptive localization of the limb and allows for a better visual to
      kinesthesic feedback.

PMID- 7621367
TI  - Postural adjustments associated with different unloadings of the forearm: effects
      of proprioceptive and cutaneous afferent deprivation.
AB  - Postural adjustments to imposed (passive) and voluntary (active) unloading
      conditions of the forearm were studied in normal subjects and a deafferented
      patient. The latency of the postural behaviour (deactivation of the biceps
      supporting the weight) was linearly related to the displacement amplitude of the
      unloaded forearm, independent of the unloading conditions. The postural behaviour
      consisted of an anticipatory postural adjustment (APA) occurring prior to active
      unloading (in both normals and the patient) and conversely in an unloading reflex
      response following passive unloading (only in the normals). In both the
      deafferented and the normal subjects, the amplitudes of the displacement during
      active unloadings were much smaller (3x) than in the passive conditions and an
      APA was present in both the deafferented and the normal subjects. The APA could
      not be triggered by some types of active movement and was absent when the
      movement was not directly producing the unloading. The EMG latencies of the APA
      and of the contralateral muscles used to unload were tightly coupled. However,
      the latency would sometimes be decoupled, particularly when a temporal delay was
      introduced between the active movement and the unloading in normal subjects. In
      contrast to the normal subjects, who were able to adapt quickly to an unusual
      unloading condition (produced by voluntary knee flexion), the deafferented
      patient did not show an APA in this task. It was concluded that, although the APA
      is of central origin, it cannot be generated only on the basis of internal timing
      cues and must rely on afferent information for its generation during unfamiliar
      unloading conditions.

PMID- 7621366
TI  - Proprioceptive control of interjoint coordination.
AB  - This paper reviews a series of experiments comparing intact controls with
      functionally deafferented patients to determine the role of proprioception in
      controlling dynamic interactions between limb segments during movement. We
      examine the control of hand path in a planar movement-reversal task and in a
      familiar three-dimensional gesture with similar biomechanical characteristics. In
      the planar task subjects had to move their hand out and back along a series of
      straight-line segments in the horizontal plane without visual feedback. The
      lengths and directions of the target line segments were chosen to require
      different amounts of shoulder motion while requiring the same elbow excursion. In
      controls, hand paths were, as required, straight with sharp bends at the
      outermost point. In patients, however, distinctive errors appeared at movement
      reversals, consisting of widened hand paths resulting from desynchronization in
      the reversals of elbow and shoulder motions. These errors reflected an inability
      to program elbow muscle contractions in accord with interaction torques produced
      at the elbow by variations in acceleration of the shoulder. The reversal errors
      were substantially reduced after patients had practiced for a few trials while
      visually monitoring movements of their arm. The improvement was not limited to
      the direction where they had practiced with vision, but also extended to other
      directions in which the elbow torques were different. This suggests that practice
      with vision of the arm served to improve the general rules that subjects used to
      plan movement, rather than simply improving the performance of a specific
      response. Similar to their performance on the planar task, the patients made
      errors in interjoint coordination during unconstrained three-dimensional gestures
      with movement reversals. We conclude (i) that both the planning and the learning
      of movement required an internal model of the dynamic properties of the limb that
      takes account of interaction torques acting at different joints; (ii) that this
      internal model is normally established and updated using proprioceptive
      information; but (iii) that when proprioception is lacking, vision of the limb in
      motion partially substitutes for proprioception.

PMID- 7621368
TI  - Proprioceptive sensory codes mediating movement trajectory perception: human hand
      vibration-induced drawing illusions.
AB  - To study the organization of the proprioceptive sensory codes subserving movement
      trajectory perception, complex hand drawing illusions were elicited using various
      vibration patterns applied to the wrist muscles of nine human subjects. It was
      established that it is possible to elicit kinesthetic illusions involving
      spatially oriented lines and geometrical shapes such as rectilinear or
      curvilinear figures by activating four groups of muscle tendons at the wrist
      level. The vibration sequences specifically evoking each shape were determined by
      varying the vibration frequency, the duration of each stimulus applied, and the
      vibrator onsets, and by applying the vibrations either successively or
      simultaneously. The proprioceptive coding of a trajectory can be modelled in
      terms of a series of vectors, the direction of which depends on the anatomical
      sites of the muscles that are stretched and shortened during the movement. The
      vector giving the spatial path of a movement is the sum vector of the vectors
      determined on the basis of the proprioceptive inputs originating from each
      muscle, and the modulus of the resulting vector is the instantaneous velocity of
      the movement. In line with previous cortical data, our results suggest that the
      perception of the spatial paths of limb segment movements is coded in joint space
      kinematic coordinates on the basis of the relevant ongoing proprioceptive
      information. It therefore emerges from the results of this study that muscle
      proprioception is able to generate spatiotemporal afferent patterns that may
      mediate complex cognitive operations such as those involved in the memorizing and
      recognition of motor forms.

PMID- 7621369
TI  - Proprioceptive coordination of discrete movement sequences: mechanism and
      generality.
AB  - A "discrete" movement sequence is defined as a movement with a single goal that
      involves a series of overlapping joint rotations. Reaching-and-grasping and
      throwing are examples of discrete movement sequences. The central nervous system
      (CNS) can use reafferent proprioceptive information from one joint rotation in a
      sequence to coordinate subsequent rotations at other joints. The experiments
      reported in this paper demonstrate how the human CNS uses proprioceptive
      information to coordinate discrete movement sequences. We examined the mechanism
      (at an information processing level) underlying proprioceptive coordination and
      the generality (i.e., the boundary conditions) of these mechanisms as they apply
      to everyday movement sequences. Adult human subjects performed a discrete
      movement sequence that resembles backhand throwing: elbow extension followed by
      hand opening. The task was to open the hand as the elbow passed through a
      prescribed "target" angle. We eliminated visual information and made the arrival
      time at the target angle unpredictable so that the available kinematic
      information was provided exclusively by proprioception. The subjects were capable
      of performing this motor task with a high degree of precision, thereby
      demonstrating that the nervous system can use proprioceptive input to coordinate
      discrete movement sequences. Our data indicate that precise coordination is
      achieved by extracting kinematic information related to both the velocity of
      elbow rotation as well as the elbow position during movement (i.e., "dynamic
      position"). Dynamic position information appears to be encoded as both absolute
      joint angle and angular distance, although more precisely as angular distance.
      Although our experiments were conducted under rather restrictive laboratory
      conditions, this mechanism of motor coordination might also apply to everyday
      movement. Our results suggest that this mechanism could be employed for passive
      as well as active movement sequences, with and without opposing loads; it could
      exert its influence in discrete movement sequences as brief as 210 ms or as long
      as 1.5 s; and it does not involve any significant degree of learning (this
      proprioceptive mechanism appears to be readily available for use on the first
      attempt of a novel motor task).

PMID- 7621371
TI  - Talking the talk--and walking the walk: community development in western
      Manitoba.

PMID- 7621370
TI  - Control variables and proprioceptive feedback in fast single-joint movement.
AB  - Sensorimotor mechanisms were studied on the basis of kinematic and
      electromyographic data as well as the static torque developed by the muscles as a
      function of joint angle. The latter relationship is known as the torque/angle
      characteristic. Fast single-joint movement may result from a shift in this
      characteristic and a change in its slope. Such movements were studied at the
      wrist in 9 normal and 1 deafferented subject. After training to flex the wrist to
      a target, subjects repeated the same movements but in random test trials
      movements were opposed by the load generated by linear position feedback to a
      torque motor. At the end of the loaded trials, the load was suddenly removed. In
      the second experiment, subjects made wrist movements to the target that were
      opposed by the load and, on random test trials, the movements were not loaded. In
      these test trials, the wrist arrived in a static position outside the target
      zone. In both experiments, subjects were instructed not to correct errors. The
      final torque/angle characteristics specified in the movements were reconstructed
      on the basis of the static wrist positions and torques before and after
      unloading. Normal subjects made movements by shifting the position of the
      torque/angle characteristic and by increasing its slope. If subjects indeed
      maintained the same pattern of control variables (descending commands), the same
      final position of the characteristic would be reproduced from trial to trial
      regardless of load perturbations. This assumption of equifinality was tested by
      comparing the final position of the wrist in nonloaded movements with that after
      removal of the load in loaded movements. Equifinality was observed in normal
      subjects. Movements in the deafferented subject were also associated with a shift
      of the torque/angle characteristic and a change in its slope. However, she was
      unable to consistently reproduce its final position. In spite of muscle
      coactivation, her maximal stiffness was lower than in normal subjects. In the
      absence of vision, the subject made movements with the load by increasing the
      slope of the characteristic instead of by shifting its position far enough. Load
      perturbation affected her final wrist position (inequifinality), which may
      reflect the presence of a significant hysteresis of the characteristic as a
      result of the absence of stretch reflexes. The deficits following deafferentation
      presumably result from the destruction of biomechanical and sensorimotor
      mechanisms including the ability of control variables to specify the positional
      frame of reference for afferent and descending systems.

PMID- 7621372
TI  - Nursing intervention studies: issues related to change and timing.
AB  - A variety of challenges confront clinicians and researchers involved in
      developing and testing nursing interventions or programs for children and their
      families. Many of these challenges relate to the issues of change and timing.
      This paper discusses some of the critical questions that must be considered when
      designing and evaluating interventions with this particular population. Issues
      are illustrated with examples from a study that tested the effectiveness of a
      nursing intervention (based on the McGill Model of Nursing) in improving the
      psychosocial adjustment of chronically ill children. The authors propose that
      careful consideration of these questions will improve the design of intervention
      studies, the evaluation of their outcomes, as well as contribute to the
      development of our knowledge in this domain.

PMID- 7621373
TI  - Indicators of exposure to wife abuse.
AB  - Data collected via a telephone survey of 406 randomly selected married (including
      common-law) women were analyzed with respect to 30 potential indicators of
      exposure to wife abuse. Women who reported exposure to wife abuse within the
      previous year were more likely than women free of abuse to have terminated their
      marriage, to have visited an emergency room, to have been hospitalized, and to
      have contacted public health nurses, psychiatrists, and psychologists, in the
      preceding year. They also were more likely to have sustained large bruises,
      lacerations, sprains or strains, and to have more frequent headaches and
      backaches, psychiatric morbidity, and alcoholism than women free of abuse. The
      abused women were likely to have more education than their partners, relatively
      lower total household incomes, and partners who were unemployed. Knowledge of
      significant indicators can facilitate the identification of women who have
      experienced wife abuse and lead to the development of more effective screening
      protocols.

PMID- 7621374
TI  - Characteristics of families--implications for statistical analysis in family
      nursing research.

PMID- 7621375
TI  - [Concepts of AIDS in relation to health and illness in homosexual men living in
      Quebec with AIDS].
AB  - Herzlich's (1969) theoretical framework was used to explore Acquired Immune
      Deficiency Syndrome (AIDS) from the point of view of affected individuals.
      Content analysis was performed on transcripts of interviews with eight French
      Canadian gay men living with AIDS. Results indicate that health and illness are
      socially constructed concepts and that health can coexist with illness. The
      authors discuss how Herzlich's framework can be used by nurses to better
      understand the individual's experience of illness and to guide the individual
      towards making behavioural changes that will generate health throughout the
      course of the illness.

PMID- 7621376
TI  - The practice of family nursing care: still a challenge!

PMID- 7621377
TI  - Data sharing in nursing research: advantages and challenges.
AB  - The sharing of data between investigators has received little attention in the
      nursing literature. Among other advantages, data sharing reinforces open
      scientific inquiry, encourages the development of multiple perspectives, and
      reduces respondent burden. However, ownership and control of the shared data,
      preservation of respondents' anonymity, and the costs of data sharing are among
      the issues that need to be addressed in agreements and contracts involving
      primary investigators, secondary investigators, and data repositories. The
      original researcher must spend time and energy to make data sharing possible. It
      is only when such efforts are acknowledged and rewarded that data sharing is
      likely to become a norm in the nursing profession. The authors argue that
      research data should be shared and nurse researchers should seek to have data
      from all publicly funded projects deposited in accessible data repositories.
      Nurse researchers need to incorporate plans for data sharing into their research
      programs and press for the infrastructures required to enable data sharing.

PMID- 7621378
TI  - Canadian First Nations women's beliefs about pregnancy and prenatal care.
AB  - Evidence links adequate prenatal care to improved birth outcomes. Research,
      however, indicates that First Nations women do not attend regularly for prenatal
      care. In the current study, seven informants, representing three First Nations
      tribes, were extensively interviewed to examine their beliefs about pregnancy and
      participation in prenatal care. First Nations women conceptualized pregnancy in a
      spiritual context and believed it to be a healthy, natural process requiring no
      intervention. Since they believed they were responsible for "taking care of
      themselves" during pregnancy, cultural practices that were thought to promote a
      healthy pregnancy were espoused. First Nations women were reportedly often
      dissatisfied with health-care providers in prenatal clinics. Their expectations
      of freely offered explanations and a friendly non-authoritarian approach were
      often not realized and their beliefs about pregnancy were in conflict with those
      of health-care providers. Barriers to prenatal care might be reduced by improving
      communication and providing holistic culture-specific care.

PMID- 7621379
TI  - The ORNAC legacy: reflections on the association's roots with an eye to the
      future. Operating Room Nurses Association of Canada.

PMID- 7621381
TI  - Position paper of the Ordre des infirmieres et infirmiers du Quebec.
      Perioperative nursing care: the function of the nurse as first assistant.

PMID- 7621380
TI  - Laparoscopic transperitoneal nephrectomy.

PMID- 7621382
TI  - National survey report on the PNA and PNS roles.

PMID- 7621383
TI  - RN first assistant: the perioperative role of the future.

PMID- 7621384
TI  - The ethics of placebo-controlled trials.

PMID- 7621385
TI  - The use of placebos in clinical trials for acute schizophrenia.
AB  - This review examines the scientific and ethical justification for the use of
      randomized concurrent placebo-controlled trials in the treatment of acute relapse
      in chronic schizophrenia. A literature search was conducted, and the national
      regulatory authority was consulted. Many placebo-controlled studies of acute or
      chronic schizophrenia are being published and it is the official position of both
      the Canadian and US regulatory authorities that such studies are required for
      both scientific and ethical reasons. The specific strengths and limitations of
      placebo-controlled studies are reviewed. Examples, drawn from Canadian studies,
      are presented to illustrate their benefits. It is concluded that the use of
      placebos in the particular situation of acute or chronic schizophrenia is
      ethically and scientifically justified. It forms an essential component of a
      comprehensive drug evaluation for new antipsychotic medications.

PMID- 7621386
TI  - Post-traumatic stress disorder in prisoners of war and combat veterans of the
      Dieppe Raid: a 50-year follow-up.
AB  - OBJECTIVE: This paper presents the first 50-year study of the differential
      effects of incarceration and combat on the development and persistence of post
      traumatic stress disorder (PTSD) in Canadian veterans and prisoners of war (POWs)
      from the Dieppe Raid. METHOD: A large sample of Dieppe POWs and nonPOWs completed
      a questionnaire diagnosing PTSD and other psychological and health problems of
      the veterans in 1946 and in 1992. RESULTS: The POWs showed a higher incidence of
      PTSD and other psychological symptoms than veterans with the same combat
      exposure. The POWs' experiences of malnutrition, maltreatment and torture, and
      mental suffering showed strong links to PTSD. CONCLUSIONS: For many veterans,
      PTSD has lasted 50 years. Failure to be eligible for psychological disability
      pensions demonstrates that PTSD and other psychological disorders in these
      veterans have been greatly unrecognized by the Canadian Department of Veteran's
      Affairs.

PMID- 7621387
TI  - Prevalence of dissociative symptoms and disorders in an adult psychiatric
      inpatient population in Canada.
AB  - OBJECTIVE: This study attempted to estimate the prevalence of dissociative
      symptoms and disorders in a Canadian adult psychiatric inpatient population and
      also attempted to determine the extent to which dissociative disorders were
      recognized by the attending clinical staff. METHOD: All appropriate and
      consenting adult psychiatric inpatients at the Kingston Psychiatric Hospital in
      Kingston, Ontario, were given the Dissociative Experiences Scale. Patients
      scoring 25 or greater were interviewed with the Dissociative Disorders Interview
      Schedule and the Structured Clinical Interview for DSM-IV Dissociative Disorders.
      Admission or discharge diagnoses data were used to determine whether or not
      dissociative disorders were being recognized. RESULTS: A total of 48 patients
      completed the Dissociative Experiences Scale and 14 (29%) scored 25 or greater.
      The prevalence of dissociative disorders in this hospital population was
      estimated to be 17%. Dissociative identity disorder was found in six percent,
      dissociative amnesia in eight percent and dissociative disorder not otherwise
      specified in two percent of the population. These disorders tended to be under
      recognized. CONCLUSION: Research on more extensive populations is required to
      establish the true prevalence of dissociative symptoms and disorders in
      psychiatric inpatients.

PMID- 7621388
TI  - Clomipramine treatment and behaviour therapy with agoraphobic women.
AB  - The separate and combined effects of clomipramine hydrochlorzide and behaviour
      therapy on agoraphobic symptoms were investigated in a 28-week placebo-controlled
      double-blind clinical trial. One hundred and eight women diagnosed as agoraphobic
      were randomly assigned to one of four treatment conditions: clomipramine alone,
      behaviour therapy alone, clomipramine and behaviour therapy or placebo. Sixty
      women completed the assigned treatment. Clomipramine was prescribed in weekly
      increments to a maximum of 300 mg per day, with a mean dosage at week 8 of 94.6
      mg per day. Behaviour therapy focused on graded in vivo exposure therapy.
      Assessments of patients were performed at six points prior to and during the
      trial and included standardized questionnaires, daily diaries and a Behavioral
      Approach Test. Significant main effects for both clomipramine and behaviour
      therapy on 15 and 12 of the dependent measures respectively were found but no
      interaction of treatments emerged.

PMID- 7621389
TI  - The correlates of cortical sulci atrophy and central atrophy in a cohort of
      schizophrenia and manic subjects in Nigeria.
AB  - The prevalence of brain cortical sulci atrophy and central (subcortical) atrophy
      among Nigerian psychiatric patients is highlighted and compared with findings
      from developed countries. The relationship between these indices of brain atrophy
      and clinical parameters is also examined. Visual ratings of cortical sulci
      atrophy and central (subcortical) atrophy, assessed on the computed tomography
      (CT) image console, were compared among 50 patients with schizophrenia, 14
      patients with mania and 41 healthy control subjects. The patients with
      schizophrenia and the patients with mania had a significantly higher prevalence
      of brain atrophy than normal subjects. Among the patients with schizophrenia,
      indices of brain atrophy were not significantly associated with disease outcome,
      and the presence of negative symptoms. In view of the findings from a parallel
      study of the same patients that psychiatric patient groups showed other evidence
      of CT abnormalities, the findings of this study indicate that the so-called
      functional psychiatric states in developing countries--as in developed countries-
      are probably associated with some diffuse neuropathological process.

PMID- 7621390
TI  - The influence of gonadal hormones on periodicity of obsessive-compulsive
      disorder.
AB  - OBJECTIVE: This paper reviews the evidence linking gonadal hormones and obsessive
      compulsive disorder (OCD) symptoms. METHOD: Four case reports of the relationship
      between obsessive-compulsive disorder symptoms and exogenous sex hormone changes
      are presented. These cases are reviewed within the context of other case reports
      and the literature on the relationship between serotonin, gonadal hormones and
      OCD. RESULTS: The authors suggest that there is a relationship between onset or
      exacerbation of OCD and changes in gonadal hormones. CONCLUSION: Clinicians
      should carefully evaluate patients for exogenous and endogenous changes in
      gonadal hormones when evaluating onset or exacerbation of OCD.

PMID- 7621391
TI  - A clinical study of clozapine treatment and predictors of response in a Canadian
      sample.
AB  - OBJECTIVE: To study the clinical response to clozapine in patients with
      refractory schizophrenia. METHOD: Open trial of clozapine in 61 consecutively
      treated patients. RESULTS: Following clozapine, the level of function of patients
      was improved relative to admission (p = 0.0001) and to the highest level in the
      previous year (p = 0.0001). Severity of illness was decreased (p = 0.0001).
      Overall, 31% of the patients were classified as responders to clozapine and the
      responders were all identified by 32 weeks of treatment. Poor functioning in the
      previous year was associated with less favourable response. At a mean interval of
      26 months following discharge, 72% of the patients were continuing clozapine
      treatment. CONCLUSIONS: This open trial of patients who were treated
      consecutively indicates a comparable degree of response to clozapine as observed
      in controlled clinical trials, and that level of functioning in the previous year
      was the best predictor of response.

PMID- 7621392
TI  - [Reflections of assisted suicide and euthanasia].

PMID- 7621393
TI  - Nefazodone-induced mania.

PMID- 7621394
TI  - Borderline personality disorder and the family environment.

PMID- 7621395
TI  - Valproate in the treatment of mood disorder due to multiple sclerosis.

PMID- 7621396
TI  - Job satisfaction of psychiatrists in public psychiatric hospitals.

PMID- 7621397
TI  - Plasma phenylethylamine levels of schizophrenic patients.

PMID- 7621398
TI  - Fungal allergens.
AB  - Airborne fungal spores occur widely and often in far greater concentrations than
      pollen grains. Immunoglobulin E-specific antigens (allergens) on airborne fungal
      spores induce type I hypersensitivity (allergic) respiratory reactions in
      sensitized atopic subjects, causing rhinitis and/or asthma. The prevalence of
      respiratory allergy to fungi is imprecisely known but is estimated at 20 to 30%
      of atopic (allergy-predisposed) individuals or up to 6% of the general
      population. Diagnosis and immunotherapy of allergy to fungi require well
      characterized or standardized extracts that contain the relevant allergen(s) of
      the appropriate fungus. Production of standardized extracts is difficult since
      fungal extracts are complex mixtures and a variety of fungi are allergenic. Thus,
      the currently available extracts are largely nonstandardized, even
      uncharacterized, crude extracts. Recent significant progress in isolating and
      characterizing relevant fungal allergens is summarized in the present review.
      Particularly, some allergens from the genera Alternaria, Aspergillus, and
      Cladosporium are now thoroughly characterized, and allergens from several other
      genera, including some basidiomycetes, have also been purified. The availability
      of these extracts will facilitate definitive studies of fungal allergy prevalence
      and immunotherapy efficacy as well as enhance both the diagnosis and therapy of
      fungal allergy.

PMID- 7621401
TI  - Measles control in the United States: problems of the past and challenges for the
      future.
AB  - Elimination of indigenous measles from the United States has been a public
      priority since 1978. To assess the progress made toward this goal, we review the
      epidemiology of measles from 1963 to the present. From the 1970s through early
      into the recent measles epidemic, the majority of measles cases were in highly
      vaccinated, school-age children. This was due primarily to a 1 to 5% primary
      measles-mumps-rubella vaccine failure rate and nonrandom mixing patterns among
      school-age populations. To eliminate susceptible individuals in the school-age
      populations, a second dose of measles vaccine is now recommended between 5 and 6
      years or 11 and 12 years by both the Advisory Committee on Immunization Practices
      and the American Academy of Pediatrics. Later in the epidemic, measles cases
      surged among unimmunized preschool children, especially among the poor in inner
      city areas. Immunization rates have been documented to be low among preschool
      populations because of missed opportunities to administer vaccines at all health
      visits and barriers to access to immunizations. To raise immunization rates, the
      age for the first measles-mumps-rubella immunization was lowered to 12 to 15
      months of age, federal immunization funding has increased, and new standards for
      immunization delivery have been developed and promulgated.

PMID- 7621400
TI  - The dermatophytes.
AB  - The etiologic agents of the dermatophytoses (ringworm) are classified in three
      anamorphic (asexual or imperfect) genera, Epidermophyton, Microsporum, and
      Trichophyton. Species capable of reproducing sexually belong in the teleomorphic
      genus, Arthroderma, of the Ascomycota. On the basis of primary habitat
      association, they may be grouped as geophilic (soil associated), zoophilic, and
      anthropophilic. Adaptation to growth on humans by most geophilic species resulted
      in diminished loss of sporulation, sexuality, and other soil-associated
      characteristics. The dermatophytes have the ability to invade keratinized tissue
      (skin, hair, and nails) but are usually restricted to the nonliving cornified
      layer of the epidermis because of their inability to penetrate viable tissue of
      an immunocompetent host. However, invasion does elicit a host response ranging
      from mild to severe. Acid proteinases, elastase, keratinases, and other
      proteinases reportedly act as virulence factors. The development of cell-mediated
      immunity correlated with delayed hypersensitivity and an inflammatory response is
      associated with clinical cure, whereas the lack of or a defective cell-mediated
      immunity predisposes the host to chronic or recurrent dermatophyte infection.
      Chronic dermatophytosis is mostly caused by Trichophyton rubrum, and there is
      some evidence that mannan produced by this fungus suppresses or diminishes the
      inflammatory response. Since dermatophytes cause a communicable disease, modes of
      transmission and control are discussed as well as a survey of recent trends in
      therapy. Collection of specimens, culture media, and tests for identification are
      also presented. Genetic studies have led to an understanding of incompatibility
      mechanisms, pleomorphism and variation, resistance to griseofulvin, and
      virulence. Molecular biology has contributed to our knowledge of the taxonomy and
      phylogenetic relationships of dermatophytes.

PMID- 7621404
TI  - DLD-1 and HCT-15 cell lines derived separately from colorectal carcinomas have
      totally different chromosome changes but the same genetic origin.
AB  - Aneuploid DLD-1 and HCT-15 cell lines independently derived from a colon
      carcinoma by two researchers lacked a common marker chromosome or a concurrent
      numerical change. To further look into the genetic identity of these two cell
      lines, we used chromosome painting with fluorescence in situ hybridization (FISH)
      and confirmed the G-band identification on all chromosome changes. We have also
      found comparable results between these two cell lines on C-/Q- polymorphic bands
      of several chromosomes, and electrophoretic patterns of restriction fragment
      length polymorphisms (RFLPs) from eight Y-chromosome-specific DNA probes with 13
      restriction enzymes. These results strongly suggest that DLD-1 and HCT-15 are
      identical genetically. Clearly, cell lines bearing totally unrelated changes in
      karotypes can be generated from the same cancer specimen.

PMID- 7621399
TI  - Tuberculosis in the AIDS era.
AB  - A resurgence of tuberculosis has occurred in recent years in the United States
      and abroad. Deteriorating public health services, increasing numbers of
      immigrants from countries of endemicity, and coinfection with the human
      immunodeficiency virus (HIV) have contributed to the rise in the number of cases
      diagnosed in the United States. Outbreaks of resistant tuberculosis, which
      responds poorly to therapy, have occurred in hospitals and other settings,
      affecting patients and health care workers. This review covers the pathogenesis,
      epidemiology, clinical presentation, laboratory diagnosis, and treatment of
      Mycobacterium tuberculosis infection and disease. In addition, public health and
      hospital infection control strategies are detailed. Newer approaches to
      epidemiologic investigation, including use of restriction fragment length
      polymorphism analysis, are discussed. Detailed consideration of the interaction
      between HIV infection and tuberculosis is given. We also review the latest
      techniques in laboratory evaluation, including the radiometric culture system,
      DNA probes, and PCR. Current recommendations for therapy of tuberculosis,
      including multidrug-resistant tuberculosis, are given. Finally, the special
      problem of prophylaxis of persons exposed to multidrug-resistant tuberculosis is
      considered.

PMID- 7621405
TI  - Rearrangement of chromosome 1 is a frequent finding in endometrial carcinoma. An
      in situ hybridization study in nine endometrial carcinomas.
AB  - Nine endometrial carcinomas were examined for numerical aberrations of the
      chromosomes 1,7, and X by fluorescence in situ hybridization using highly
      repetitive chromosome-specific probes. In addition, a combination of a
      centromeric and a telomeric chromosome 1 probe was applied to detect structural
      chromosome 1 aberrations. Chromosome aberrations were found in six tumors. In
      four of these, an imbalance between 1q12 and 1p36 was detected, indicating the
      presence of an extra 1p- chromosome. In regard to the chromosomes 7 and X,
      monosomies and trisomies were found. Intratumoral genetic heterogeneity in
      endometrial carcinomas was detectable by FISH and flow cytometry. In conclusion,
      our findings confirm that chromosome 1 is frequently involved in structural
      chromosome changes, indicating chromosome 1 to be of importance in the evolution
      of endometrial carcinoma.

PMID- 7621406
TI  - Reversed BCR/ABL rearrangement detected by FISH in Philadelphia negative chronic
      myelocytic leukemia.
AB  - We investigated leukemic cells from a patient with chronic myelocytic leukemia
      (CML) and a normal 46,XX karyotype. Molecular studies revealed rearrangement of
      the M-bcr region and formation of BCR/ABL fusion mRNA with b3a2 configuration.
      Fluorescence in situ hybridization (FISH) using the abl probe showed signal on
      both chromosomes 9 band q34, while the bcr probe hybridized to one chromosome 22
      and to one chromosome 9. In this case, as in three other cases recently described
      (Hagemeijer et al. and Nachava et al.), the bcr/abl rearrangement is shown to be
      on 9q34, instead of the usual location on 22q11.

PMID- 7621407
TI  - Molecular cytogenetic analysis of a t(7;10) in a human glioblastoma cell line.
AB  - Glioblastoma multiforme (GBM) is the most malignant glial brain tumor in humans.
      The fact that deleted copies of chromosome 10 are observed frequently in primary
      GBM tumors supports the hypothesis that one or more tumor suppressor genes
      located on chromosome 10 occupy crucial growth control checkpoints for glial
      cells. Deletion mapping in primary GBM tumors using the loss of heterozygosity
      (LOH) test has implicated the 10q24-10qter region as one possible site for a
      gene. We report here on the molecular cytogenetic analysis of chromosome 10
      abnormalities in a human GBM cell line, JBSA. LOH testing showed that JBSA cells
      were hemizygous for chromosome 10. Molecular cytogenetic analysis showed that the
      undeleted homologue was involved in a reciprocal translocation t(7;10)(p21;q22).
      The translocation breakpoint on chromosome 10 lay within band q22 between D10S19
      and D10S4. The fact that JBSA cells lack one homologue of chromosome 10 and carry
      a translocation breakpoint on the remaining one, proximal to the smallest region
      of overlap reported in primary tumor deletions, suggests that 10q22 may be
      another possible site for a tumor suppressor gene involved in GBM.

PMID- 7621408
TI  - Chromosomal abnormalities in 47 pediatric brain tumors.
AB  - The karyotypes of 47 pediatric brain tumors (14 cerebellar pilocytic
      astrocytomas, six cerebral pilocytic astrocytomas, seven anaplastic astrocytomas
      and glioblastomas, nine medulloblastomas [PNETs], one cerebral neuroblastoma,
      four ependymomas, and seven miscellaneous other neoplasms) are presented. Most of
      the pilocytic astrocytomas and ependymomas had normal karyotypes. In contrast,
      the majority of the anaplastic astrocytomas-glioblastomas were abnormal. The
      abnormalities included losses and structural abnormalities of chromosomes 9, 13,
      and 17, and double minutes. There were no losses of chromosomes 10 and 19q or
      gains of chromosome 7, which are among the most common abnormalities of adult
      glioblastomas. The chromosomal abnormalities in the medulloblastomas were similar
      to those reported in the literature but less frequent. Four tumors (choroid
      plexus papilloma, meningioma, cerebral malignant rhabdoid tumor, and immature
      teratoma) had losses of chromosome 22.

PMID- 7621410
TI  - Cytogenetics of gastric and esophageal adenocarcinomas. 3q deletion as a possible
      primary chromosomal change.
AB  - We report clonal chromosome abnormalities in short term cultures of seven gastric
      or esophageal adenocarcinomas and two squamous carcinomas of the esophagus and EG
      junction. The most consistent aberration encountered was a del(3) (q13.2q23) seen
      in six of nine tumors. This finding, together with a survey of published
      cytogenetic literature, suggested that del(3q) is the most common cytogenetic
      abnormality, and hence possibly of primary significance, in these tumors. In
      addition to del(3q), rearrangements affecting 1p13 (two cases), 6q15-q23 (two
      cases), 7p22 (two cases), 7q22 (two cases), and 11p11.2-p14 (three cases) were
      seen. Cytogenetic evidence for gene amplification in the form of homogeneously
      staining region (hsr) was seen at 9q13 in two cases.

PMID- 7621409
TI  - Clonal karyotypic evolution in a pediatric neurofibrosarcoma.
AB  - A retroperitoneal neurofibrosarcoma infiltrating the spine of a 2-year-old boy
      was investigated cytogenetically three times over a 5-month period. The first
      sample, from a diagnostic fine-needle aspiration biopsy, had a supernumerary
      i(1)(q10) as the sole clonal aberration; two cells showed monosomy 18 in addition
      to the isochromosome. The second sample, obtained at tumor resection 3 weeks
      later, had the karyotype 47,XY, +i(1)(q10), -18, +21/45,XY, -18. After 5 months,
      a large local recurrence was resected. The chromosome analysis showed further
      clonal evolution: 45,XY, +1,der (1;11)dic(1;11)(q44;q13)i(1)(q10),
      inv(6)(p21q12), -17. The findings indicate that formation of i(1)(q10) and loss
      of chromosome 18 may be early genetic events in neurofibrosarcoma development.

PMID- 7621411
TI  - A group of NotI jumping and linking clones cover 2.5 Mb in the 3p21-p22 region
      suspected to contain a tumor suppressor gene.
AB  - The chromosomal region 3p21.2-p22 has been shown to be involved in the
      development of several forms of solid tumors. Such deletions, translocations, and
      rearrangements presumably result in the disturbance or loss of a critical gene
      function. Pulsed-field gel electrophoresis (PFGE), using NotI linking clones as a
      probe represent a powerful tool for analyzing such rearrangements. A NotI linking
      clone, AP20 (D3S1641), was localized by in situ hybridization to 3p21.3-p22. Two
      NotI jumping clones adjacent to this clone were isolated, clone J32-612 covering
      0.5 Mb and clone J31-611 covering approximately 1 Mb. Clone J31-611 crosses the
      border of the deletion present in hybrid cell line MCH939.2, which contains a
      deleted 3p21 region. For these jumping clones, corresponding NotI linking clones,
      NLJ3 (D3S1642) and NL3-003, were isolated. Altogether, linking and jumping clones
      from the AP20 locus hybridize to NotI fragments totaling 2.5 Mb in length. These
      NotI-containing clones detect expressed sequences in several human tissues. Clone
      NLJ3 possesses homology to the human platelet-derived endothelial cell growth
      factor gene and may represent a new member of this gene family. Another clone
      (AP20) revealed 66% sequence similarity to rat skeletal muscle voltage-sensitive
      sodium channel subtype 2. Therefore, this group of clones will be useful not only
      for analyzing rearrangements in tumors, but also for the isolation of new genes
      from the 3p21.3-p22 region.

PMID- 7621413
TI  - Prediction of 18-month survival in patients with primary myelodysplastic
      syndrome. A regression model and scoring system based on the combination of
      chromosome findings and the Bournemouth score.
AB  - The predictive potential of six selected factors was assessed in 72 patients with
      primary myelodysplastic syndrome using univariate and multivariate logistic
      regression analysis of survival at 18 months. Factors were age (above median of
      69 years), dysplastic features in the three myeloid bone marrow cell lineages,
      presence of chromosome defects, all metaphases abnormal, double or complex
      chromosome defects (C23), and a Bournemouth score of 2, 3, or 4 (B234). In the
      multivariate approach, B234 and C23 proved to be significantly associated with a
      reduction in the survival probability. The similarity of the regression
      coefficients associated with these two factors means that they have about the
      same weight. Consequently, the model was simplified by counting the number of
      factors (0, 1, or 2) present in each patient, thus generating a scoring system
      called the Lausanne-Bournemouth score (LB score). The LB score combines the well
      recognized and easy-to-use Bournemouth score (B score) with the chromosome defect
      complexity, C23 constituting an additional indicator of patient outcome. The
      predicted risk of death within 18 months calculated from the model is as follows:
      7.1% (confidence interval: 1.7-24.8) for patients with an LB score of 0, 60.1%
      (44.7-73.8) for an LB score of 1, and 96.8% (84.5-99.4) for an LB score of 2. The
      scoring system presented here has several interesting features. The LB score may
      improve the predictive value of the B score, as it is able to recognize two
      prognostic groups in the intermediate risk category of patients with B scores of
      2 or 3. It has also the ability to identify two distinct prognostic subclasses
      among RAEB and possibly CMML patients. In addition to its above-described
      usefulness in the prognostic evaluation, the LB score may bring new insights into
      the understanding of evolution patterns in MDS. We used the combination of the B
      score and chromosome complexity to define four classes which may be considered
      four possible states of myelodysplasia and which describe two distinct
      evolutional pathways.

PMID- 7621412
TI  - Molecular characterization of a (1;10)(p22;q21) constitutional translocation from
      a patient with neuroblastoma.
AB  - A constitutional t(1;10)(p22;q21) from a patient with stage IVS neuroblastoma has
      been isolated in somatic cell hybrids and the position of the breakpoints
      analyzed. On chromosome 1 the breakpoint lies in a 4-Mbp region flanked by
      minisatellite marker D1S234 and by D1S188, which lies in the region of F3. The
      chromosome 10 breakpoint lies between RBP3 and NAKNR below the MEN2 locus.
      Because, in patients with genetic disease, constitutional translocations
      frequently interrupt genes which are related to the clinical phenotype this
      rearrangement has identified two regions which potentially contain genes related
      to the development of neuroblastoma.

PMID- 7621403
TI  - Virus receptors: implications for pathogenesis and the design of antiviral
      agents.
AB  - A virus initiates infection by attaching to its specific receptor on the surface
      of a susceptible host cell. This prepares the way for the virus to enter the
      cell. Consequently, the expression of the receptor on specific cells and tissues
      of the host is a major determinant of the route of entry of the virus into the
      host and of the patterns of virus spread and pathogenesis in the host. This
      review emphasizes the virus-receptor interactions of human immunodeficiency
      virus, the rhinoviruses, the herpesviruses, and the coronaviruses. These
      interactions are often found to be complex and dynamic, involving multiple sites
      or factors on both the virus and the host cell. Also, the receptor may play an
      important role in virus entry per se in addition to its role in virus binding. In
      the cases of human immunodeficiency virus and the rhinoviruses, ingenious
      approaches to therapeutic strategies based on inhibiting virus attachment and
      entry are under development and in clinical trials.

PMID- 7621414
TI  - Cytogenetic findings in a case of nodular fasciitis of the breast.
AB  - We report the cytogenetic findings in a case of nodular fasciitis of the breast.
      The abnormalities found in all 11 metaphases available for analysis were -2, -2, 
      13, der(15)t(2;15)(q31;q26), + der(?) t(?;2), + mar1, + mar2. Other consistent
      abnormalities were also identified. Fluorescence in situ hybridization (FISH) was
      used to confirm the origin of some of the chromosomes. A large acrocentric
      chromosome was confirmed to be derived from chromosome 15 with chromosome 2
      material translocated onto the q arm. The metacentric der(?)t(?;2) was
      demonstrated to have part of chromosome 2 on the q arm. No other chromosome 2
      material was found. Eight of 11 cells were tetraploid and had two copies of a
      del(6)(q16q24).

PMID- 7621415
TI  - Cytogenetic study of 11 gastric adenocarcinomas.
AB  - We describe the cytogenetic findings in 11 gastric cancer cases. Nine cases
      showed a variable number of numerical and structural aberrations, while two cases
      had a normal karyotype. The chromosomes most frequently involved are chromosome 3
      in six cases, 6 in four cases, and 13 in three cases. They mainly exhibited
      structural aberrations. An additional segment on chromosome 3p was observed in
      three cases, while two cases had a del(3q). A der(5) chromosome resulting from a
      translocation between chromosomes 3 and 5 was observed in two cases. Both cases
      had also a del(6q), a der(12), and an add(17p) chromosome as common
      abnormalities. Deletion of 6q chromosome distal to band 6q21 was observed in
      three cases. Trisomy 8 as a sole anomaly was found in one case. Our cytogenetic
      findings are discussed in relation to the reported in the literature data.

PMID- 7621416
TI  - Absence of mutation at the GAP-related domain of the neurofibromatosis type 1
      gene in sporadic neurofibrosarcomas and other bone and soft tissue sarcomas.
AB  - The NF1 gene encodes neurofibromin, a GTPase-activating protein containing a GAP
      related domain (NF1-GRD) that is capable of downregulating ras by stimulating ras
      intrinsic GTPase activity. We tested 44 sarcomas, nine of which corresponded to
      sporadic neurofibrosarcomas, for mutations at the NF1-GRD by the polymerase chain
      reaction-single strand conformation polymorphism (PCR-SSCP) technique, finding no
      mutation in every sample tested. We suggest that inactivation of the NF1-GRD by
      gene mutation seems not to be an important event in the tumorigenesis of
      sarcomas.

PMID- 7621417
TI  - Inversion(10)(q11q24) in a case of adult T-cell leukemia.
AB  - We report a case of adult T-cell leukemia (ATL) with complex chromosome
      abnormalities including an inversion (10)(q11q24) in a 64-year-old man. Although
      some abnormalities of chromosome 10 have been seen in ATL and other lymphoid
      neoplasias, inv(10)(q11q24) has previously been reported only in a case of T-cell
      chronic lymphocytic leukemia. Recent studies have revealed a rearrangement of a
      novel homeobox-containing gene called TCL-3 or HOX11 on 10q24 in T-cell acute
      lymphoblastic leukemia with the specific chromosome translocation
      t(10;14)(q24;q11), and thus the significance of 10q24 aberrations in
      leukemogenesis is indicated. We suggest that, despite the rarity of this anomaly,
      inv(10) (q11q24) may be a new chromosome inversion related to T-cell neoplasia
      and that the 10q24 anomaly may be an important cytogenetic clue for the
      elucidation of the pathogenesis of some peripheral T-cell neoplasias.

PMID- 7621402
TI  - Endotoxemia: methods of detection and clinical correlates.
AB  - As an assay for endotoxin, the Limulus amebocyte lysate assay has several
      desirable properties: sensitivity, specificity, and potential for adaptation to a
      quantitative format. Several modifications have been developed to enhance its
      potential for clinical application. The modifications that allow quantitative
      measurement of endotoxin and also improve its application to blood samples are
      described in this review. In fluids other than blood, the detection of endotoxin
      with the Limulus amebocyte lysate assay can be used as an aid to identify the
      presence of gram-negative bacteria, and the assay has established utility. With
      blood, however, there are a range of factors that interfere with the detection of
      endotoxemia and there are disparate views with respect to the diagnostic and
      prognostic significance of the test results. In general, the clinical
      significance of the finding of endotoxemia broadly parallels the frequency and
      importance of gram-negative sepsis in the patient groups studied and a decline in
      endotoxin levels accompanies clinical improvement. However, with therapies
      designed to reduce levels of endotoxin, or to antagonize its effects, it is
      unclear whether clinical improvement occurs as a consequence of changes in the
      levels of endotoxemia.

PMID- 7621418
TI  - Isochromosome 6p and deletion of 6q characterize two related cytogenetic clones
      in a patient with immunoblastic lymphoma.
AB  - In a case of immunoblastic lymphoma we observed the presence of either a deletion
      of the long arm of chromosome 6 or of an isochromosome, i(6p), which occurred
      alternatively in metaphase cells. This suggests a selective pressure for loss of
      heterozygosity of genes located on 6q and is in accordance with the hypothesis
      that one or more tumor suppressor genes might be located on the long arm
      chromosome 6.

PMID- 7621419
TI  - Patterns of clonal evolution in transformed chronic myelogenous leukemia.
AB  - Chronic myelogenous leukemia (CML) is an initially indolent disease which
      transforms into an acute leukemia about 2-5 years after diagnosis. We report a
      series of 75 patients, from a total of 125 patients with CML, who underwent acute
      blastic transformation. These included four unclassified, 10 lymphoid, and 61 non
      lymphoid acute leukemias, including 54 myeloblastic, three promyelocytic, one
      myelomonocytic, one erythroblastic, and two megakaryoblastic leukemias. Fifty-two
      patients developed new cytogenetic abnormalities in addition to being Ph
      positive. These included trisomies of chromosomes 8, 19, and 21, isochromosome of
      the long arm of chromosome 17 (i(17q)), double and triple Ph, as well as other
      translocations, deletions, and additions. The overall median survival once the
      diagnosis of acute blast crisis was made was 61 days.

PMID- 7621420
TI  - Trisomy 13 in a patient with a myelodysplastic syndrome.

PMID- 7621421
TI  - New rearranged chromosomes t(2;3), t(7;14), t(8;11), and t(7;12;14), in a case of
      T-cell chronic lymphocytic leukemia.

PMID- 7621422
TI  - Combination adriamycin and suramin induces apoptosis in bcl-2 expressing prostate
      carcinoma cells.
AB  - Bcl-2 expression has been associated with progression of prostate cancer from
      androgen-dependence to androgen-independence and may contribute to the relative
      drug-resistant phenotype typically observed in androgen-independent prostate
      cancer. Dunning-G rat prostate cancer cells transfected with a bcl-2 expression
      vector demonstrated resistance to apoptosis induced by adriamycin and, to a
      lesser extent, suramin. Use of adriamycin and suramin in combination, however,
      circumvents this bcl-2 associated drug resistance. Our findings indicate that
      combination drug actions may induce apoptosis in resistant malignant cell types
      with defective apoptotic pathways.

PMID- 7621423
TI  - Effects of antioxidants on the anti-proliferation induced by protein synthesis
      inhibitors in human brain tumor cells.
AB  - The effects of protein synthesis inhibitors (cycloheximide, anisomycin, puromycin
      and emetine) on the growth of human brain tumor cells were investigated using U
      373 MG human astrocytoma and SK-N-MC human neuroblastoma cell lines. These agents
      inhibited the growth of the tumor cells in a dose-dependent manner. However,
      these agents did not affect cell viability evaluated by the trypan blue exclusion
      method, indicating that growth inhibition was due to the inhibition of cell
      proliferation rather than the induction of cytotoxicity. Anti-proliferation
      induced by these agents was significantly blocked by the treatments with either
      free radical scavengers or antioxidants. These results suggest that enhanced
      oxidative stress may be involved in the anti-proliferation induced by the protein
      synthesis inhibitors in human brain tumor cells.

PMID- 7621425
TI  - Metastasis of C1300 and TBJ murine neuroblastomas correlates with expression of
      matrix metalloproteinases.
AB  - Because metalloproteinases, specifically type IV collagenases, may mediate
      metastasis, 72- and 92-kDa collagenase activities were evaluated in two murine
      neuroblastoma cell lines: non-metastatic C1300 and metastatic TBJ. Zymogram
      analysis demonstrated that 72- and 92-kDa collagenases were associated only with
      metastatic TBJ. Three human neuroblastoma cell lines were then evaluated by
      zymogram and Western blot analyses: 72-kDa collagenase was found in metastatic SK
      N-SH and IMR-32, but not in SK-N-MC, which may be a peripheral neuroectodermal
      tumor and not a neuroblastoma. Therefore, 72- and 92-kDa collagenases may be
      markers of metastasis in neuroblastoma and may aid in differentiation from other
      small blue cell tumors.

PMID- 7621426
TI  - The effects of end point overdispersions on the validity of single-dose
      tumorigenicity assays.
AB  - Overdispersion can be found in tumor incidence and tumor latency end point values
      obtained by the conventional assays that are being used to assess the
      tumorigenicity of neoplastic cells growing in tissue culture. Failure to account
      for such wide variations in end point data can lead to incorrect assessments of
      the neoplastic cell tumorigenic phenotype and misinterpretations of data relating
      genetic functions to tumor-forming capacity. This problem suggests the need for
      more detailed analyses of the relationships that exist between tumor cell dose
      and the parameters being used to measure tumorigenicity.

PMID- 7621424
TI  - Absence of cyclin D1/PRAD1 point mutations in human breast cancers and
      parathyroid adenomas and identification of a new cyclin D1 gene polymorphism.
AB  - PRAD1 (cyclin D1) has been implicated in the molecular pathogenesis of a variety
      of tumors, including parathyroid adenomas, t(11;14)-bearing B-lymphoid tumors,
      and breast cancer. The sequence of the overexpressed PRAD1 genes has been
      directly analyzed in only two tumor specimens, a benign parathyroid adenoma and a
      malignant centrocytic lymphoma. Thus, little is known about PRAD1 sequence in the
      vast majority of human primary tumors, including breast cancers. Using single
      strand conformational polymorphism (SSCP) analysis, we have examined the coding
      region of the PRAD1 gene in 30 primary breast cancers and 25 parathyroid
      adenomas. Polymerase chain reaction (PCR)-SSCP analysis of the coding region of
      exons 1-5 of the PRAD1 gene did not reveal any tumor-specific mutations. During
      the course of screening for mutations, we found and established the sequence
      variants of a new DNA polymorphism at codon 241 within exon 4 of the PRAD1 gene.
      Since this polymorphism is located within the coding region of the PRAD1 gene, it
      will allow determination of allele-specific expression of the gene and the
      detection of allele imbalance. At least in breast and parathyroid neoplasms,
      overexpression of the wild-type PRAD1 sequence, rather than point mutational
      activation, appears to be the predominant mechanism by which PRAD1 exerts its
      oncogenic action.

PMID- 7621427
TI  - Superoxide dismutase and catalase blood levels in patients with malignant
      diseases.
AB  - Superoxide dismutase (SOD) and catalase (CAT) activities have been measured in
      blood from male and female patients of different ages with several types of
      cancer, in order to examine the relationship among cancer and the two free
      radical detoxificant enzymes. SOD activity in patients with cancer was found not
      to be significantly different from the SOD activity observed in the normal
      population. CAT activity was lower in patients with cancer, especially in
      lymphomas, when compared with CAT activity in the normal population.

PMID- 7621428
TI  - Berberine complexes with DNA in the berberine-induced apoptosis in human leukemic
      HL-60 cells.
AB  - Berberine, an alkaloid initially isolated from Chinese herbal medicine exhibited
      the ability to induce morphological changes and internucleosomal DNA
      fragmentation, characteristic of apoptosis in promyelocytic leukemia HL-60 cells.
      Cell cycle studies showed that only about 20% of the cells underwent apoptosis at
      the early time (6 h) of berberine (25 micrograms/ml) treatment; these appeared to
      be cells in S phase at the time of berberine treatment. At extended time (6-48
      h), cells were cell cycle arrested, the number of cells of each phase,
      particularly the cells of S phase decreased and much more (> 50%) of the cells
      appeared with DNA content less than G1. Attempts were also made to isolate
      possible berberine-DNA complexes from cell cultures treated with berberine (25
      micrograms/ml; 2-24 h). Shifts of absorption maxima of berberine in the direction
      of longer wavelengths were observed in the isolated berberine-DNA complexes.
      Palmatine, an analog of berberine, which was not able to induce apoptosis, also
      complexed with DNA in cells treated with palmatine (25 micrograms/ml; 2-24 h).
      Our results suggest that some important cellular processes other than the
      intracellular DNA-interacting action of berberine may be involved in the
      berberine-induced apoptosis in HL-60 cells.

PMID- 7621429
TI  - 2-Mercaptopropionylglycine modulates the expression of c-jun and c-Ha-ras in
      regenerating rat liver.
AB  - Changes in the expression of two proto-oncogenes, c-jun and c-Ha-ras and their
      modulation by MPG were studied in regenerating rat liver. A significant increase
      in c-jun and c-Ha-ras mRNA levels was noted after partial hepatectomy. However,
      the increase in c-Ha-ras mRNA was much less when compared with c-jun mRNA levels.
      Metallothionein (MT-I) mRNA levels showed a gradual decrease following partial
      hepatectomy. However, the decrease in MT-I mRNA levels was not significant when
      intertime comparisons were made. MPG caused a significant reduction in the levels
      of c-jun and c-Ha-ras mRNA in the regenerating rat liver compared to untreated
      controls, but had very little effect on MT-I mRNA levels. Selective reduction in
      the expression of proto-oncogenes by MPG suggests that MPG may affect the cell
      proliferation by modulating the expression of these genes.

PMID- 7621430
TI  - Melatonin inhibition of MCF-7 human breast-cancer cells growth: influence of cell
      proliferation rate.
AB  - We have studied whether the cell proliferation rate modifies the inhibitory
      actions of melatonin on MCF-7 cell growth. The proliferative rate of cells was
      altered by plating them at different densities (5 x 10(4) to 100 x 10(4)
      cells/dish) in media with low charcoal-stripped serum concentrations. In this
      way, population doubling time ranged from 33 h (for density = 100 x 10(4)
      cells/dish) to 75 h (for density = 5 x 10(4) cells/dish). Melatonin (10(-9)M)
      only inhibited fast proliferating MCF-7 cells, increasing their cell doubling
      time, and did not significantly modify the length of doubling time in the
      cultures with low proliferation rate, in which doubling time was already long.
      These data clearly show that there is a direct relation between proliferative
      rate of cells and melatonin inhibitory actions on MCF-7 cells.

PMID- 7621431
TI  - Phosphoinositide turnover during hepatocarcinogenesis induced by N
      nitrosodiethylamine.
AB  - The metabolism of phosphatidylinositol (PI) has been examined in rat liver during
      administration of N-nitrosodiethylamine (NDEA). The activities of PI kinase and
      PIP kinase were observed to be decreased as early as 7 days from the onset of
      NDEA administration, and remained suppressed until 60 days. PI synthetase showed
      a transient increase in activity at 7 days and thereafter the activity declined.
      The level of diacylglycerol (DAG), a key second messenger, showed a steady rise
      during the period of NDEA administration. A parallel increase in DAG kinase
      activity was also apparent. The results suggest that alterations of enzymes
      central to second messenger system with resulting changes in phosphoinositide
      turnover are important events during hepatocarcinogenesis induced by NDEA.

PMID- 7621432
TI  - Attenuation of vasoactive intestinal peptide enhancement of colon carcinogenesis
      by ornithine decarboxylase inhibitor.
AB  - The effects of combined administration of vasoactive intestinal peptide (VIP) and
      the ornithine decarboxylase (ODC) inhibitor, 1,3-diaminopropane (DAP), on
      development of colon tumors induced by azoxymethane (AOM), on ODC activity of the
      colon wall, and on the labelling index of colon epithelial cells were
      investigated in inbred Wistar rats. Rats received weekly subcutaneous injections
      of AOM for 10 weeks and subcutaneous injections of VIP every other day and
      drinking water containing DAP (2.5 milligrams) ad libitum until the end of the
      experiment at week 45. Administration of VIP significantly increased the
      incidence of colon tumors at week 45. It also resulted in significant increases
      in colon ODC activity and in the labelling index during administration of AOM,
      but not after its cessation. Administration of both DAP and VIP significantly
      reduced the enhanced colon carcinogenesis by VIP. The DAP significantly
      attenuated the VIP enhancement of colon ODC activity and of the labelling index
      during AOM administration. These findings indicate that ODC inhibition attenuated
      enhancement of colon carcinogenesis, and suggest that enhancement of colon
      carcinogenesis by VIP may be mediated through its polyamine biosynthesis.

PMID- 7621433
TI  - Temperature monitoring during photodynamic therapy of skin tumors with topical 5
      aminolevulinic acid application.
AB  - Temperature monitoring during photodynamic therapy (PDT) with topical 5
      aminolevulinic acid (ALA) cream application was performed on 22 patients with
      solar keratoses (SK) and basal cell carcinoma (BCC). The lesions were located on
      the forehead, nose, ear and cheek. Temperature measurements during
      photoirradiation, with a power density of 100 mW/cm2 from an incoherent light
      source (light delivery system for PDT), were carried out by noncontact (infrared
      thermal imaging radiometer) and contact (thermocouple) methods. Thermal imaging
      analysis revealed nonuniform temperature distribution in the irradiated areas.
      The temperature gradually increased from the peripheral to the central zone of
      the area. The results showed that photoirradiation induced heating of the skin
      tumors to 39.5-42.5 degrees C during the PDT procedure. The temperature of normal
      skin areas disposed symmetrically to the lesions on the contralateral side at the
      same conditions of irradiation (without prior ALA application) was about 42-43.5
      degrees C. The surface temperature differences (delta T) between the normal and
      tumor tissues after 10 min of irradiation were 3.3 +/- 0.5 degrees C in the
      forehead areas, 2.5 +/- 0.4 degrees C in the nose areas and 0.8 +/- 0.3 degrees C
      in the ear areas.

PMID- 7621434
TI  - Switching between control and phytohaemagglutinin-containing diets affects growth
      of Krebs II ascites cells and produces differences in the levels of putrescine,
      spermidine and spermine.
AB  - Almost twice as many ascites tumour cells were recovered from mice pre-fed for 3
      days on a lactalbumin (La)-based control diet, injected with Krebs II ascites
      cells and then maintained on the same diet for a further 8 days, when compared
      with mice fed on a phytohaemagglutinin-containing (PHA) diet for the whole
      period. A dietary switch on the day of injection of tumour cells produced an
      intermediate effect; mice switched to the La diet after pre-feeding on PHA for 3
      days developed somewhat more tumour cells than when the opposite dietary switch
      was performed. The polyamine content in the tumour cells was lowest in the mice
      fed on La, and highest in mice fed PHA for the duration of the experiment,
      respectively. Since large amounts of extraneous polyamines are required in order
      to sustain tumour growth, and the hyperplastic growth of the gut which occurs in
      response to injesting the lectin is a polyamine-dependent process, it is evident
      that the two growth signals compete with one another for important
      nutrients/growth factors, including polyamines.

PMID- 7621435
TI  - Increased mRNA expression of the receptor-like protein tyrosine phosphatase alpha
      in late stage colon carcinomas.
AB  - The protein tyrosine phosphatase alpha (PTP alpha) mRNA level in paired samples
      of late stage (Dukes' D) colorectal tumors and adjacent normal colon mucosa was
      quantified by RNase protection assays. After normalization against 18S RNA or
      beta-actin mRNA level, a 2-10-fold increase in PTP alpha mRNA was detected in 10
      of 14 tumors (approximately 70%) compared to mucosa. In situ hybridization of
      digoxigenin-labelled antisense PTP alpha RNA to tumor and mucosa sections
      produced a signal only in neoplastic cells of the tumor sample, consistent with
      the high increase in PTP alpha mRNA detected by RNase protection assays of some
      of the tumors. This is the first report suggesting an association of a protein
      tyrosine phosphatase with colorectal carcinoma. PTP alpha is a receptor-like PTP
      thought to be involved in regulating cell proliferation. Its oncogenic properties
      when overexpressed in cultured fibroblasts suggest that PTP alpha overexpression
      could contribute to the tumorigenic process in colon carcinoma.

PMID- 7621436
TI  - Jun-B oncogene aberrations in cervical cancer cell lines.
AB  - We describe here structural and expression analysis of the jun-B oncogene in two
      cervical cancer cell lines. In the CC7T-a cell line, results from both Southern
      analysis and cDNA cloning studies revealed the existence of two structurally
      altered jun-B alleles besides the normal gene. One of the altered alleles was due
      to a type 16 human papillomavirus (HPV-16) integration event, whereas the other
      allele was a consequence of a chromosomal translocation involving chromosome 19
      (jun-B) and an EST182 locus residing in chromosome 15. In the HeLa cell line,
      which contains integrated HPV-18, an apparent structural aberration, a 3-fold
      amplification and a 3-fold overexpression of the jun-B gene were observed. Our
      observations suggest that deregulation of the jun-B gene expression may have
      contributed to the transformation process in these two cervical cancer cell
      lines.

PMID- 7621437
TI  - Efficacy of photodynamic therapy against doxorubicin-resistant murine tumors.
AB  - Photodynamic therapy (PDT) is a relatively new cancer treatment modality that
      employs light excitation of a photosensitizer to yield cytotoxic oxygen-related
      species. In the present study we explored whether PDT would have therapeutic
      effect against doxorubicin-resistant murine tumors. We compared the efficacy of
      PDT with aluminium disulphonated phthalocyanine (A1S2Pc) and laser light on the
      doxorubicin-sensitive murine tumors, B16 melanoma (B16), L1210 leukemia (L1210),
      P388 lymphoma (P388) and the corresponding doxorubicin-resistant lines (B16/Dx,
      L1210/Dx and P388/Dx). Mice bearing L1210-L1210/Dx, P388-P388/Dx and B16-B16/Dx,
      were treated with 5 mg/kg of A1S2Pc and laser light (100 mW/cm2 x 10 min of
      exposure) or with doxorubicin (10 or 12 mg/kg i.v.). The results show that PDT is
      active versus all tumors while doxorubicin is effective only against the three
      sensitive tumor lines (L1210, P388 and B16). These observations suggest that PDT
      might be a beneficial alternative treatment for drug-resistant tumors.

PMID- 7621438
TI  - Decreased plasma glutathione in cancer of the uterine cervix.
AB  - Plasma total glutathione (GSH) content (reduced plus oxidized) was estimated in
      varying grades of cervical intraepithelial neoplasia (CIN) and in invasive
      cervical cancer. The values were compared with age-matched control women. The
      results show significantly lower level of plasma GSH in CIN III and invasive
      cancer compared to controls (0.724 versus 1.082 and 0.622 versus 1.082 mumol/ml
      of plasma, P < 0.05). Further, the odds ratio analysis showed high plasma GSH
      content was found to be protective against the development of cervical cancer.
      The results suggest a plausible association of plasma GSH with cervical
      carcinogenesis. The quantitative changes occurring in plasma total glutathione
      during cervical carcinogenesis is a useful finding and might represent a systemic
      biochemical marker for precancerous and cancerous lesions of the uterine cervix.

PMID- 7621439
TI  - Modulating effects of ellagic acid, vanillin and quercetin in a rat medium term
      multi-organ carcinogenesis model.
AB  - Effects of dietary supplementation with the antioxidants ellagic acid, quercetin
      and vanillin were examined using a medium term multi-organ carcinogenesis model
      in rats. Groups of 10-15 male F344 rats were given i.p. injections of
      diethylnitrosamine (DEN, 100 mg/kg body wt.) and N-methylnitrosourea (MNU, 20
      mg/kg body wt), s.c. injections of 1,2-dimethylhydrazine (DMH, 40 mg/kg body
      wt.), together with 0.05% N-butyl-N-(4- hydroxybutyl)nitrosamine (BBN) and 0.1%
      2,2'-dihydroxy-di-n-propylnitrosamine (DHPN), both in the drinking water, for a
      total multiple initiation period of 4 weeks (DMBDD) treatment). Ellagic acid,
      quercetin or vanillin, each at a dose of 1% each in the diet were administered
      from 1 day before and throughout the carcinogen exposure period, or after
      completion of the initiation regimen. All surviving animals were sacrificed at
      the end of week 36, and major organs were examined histopathologically. In the
      small intestine, significant reductions in the incidence and number of tumors
      (adenomas and carcinomas) were observed in the groups administered ellagic acid
      during (8%, 0.08 +/- 0.29) or after (8%, 0.08 +/- 0.29) DMBDD treatment, and
      those receiving quercetin after DMBDD treatment (0%) compared to the control
      value (57%, 1.07 +/- 1.21). Although the incidences were not statistically
      significant, slightly decreased numbers of small intestinal tumors were found in
      the groups receiving vanillin during (0.33 +/- 0.72), or after (0.40 +/- 0.83)
      DMBDD treatment. The incidence of large intestinal carcinomas in the group
      treated with vanillin during DMBDD treatment was significantly higher (73%) than
      the control value (21%). These results indicated that while ellagic acid and
      quercetin exerted potent chemopreventive action in both the initiation and
      promotion stages in the present experimental system, their beneficial effects
      were restricted to the small intestine. Since small intestinal carcinomas are
      very infrequent in humans, the advantages of these phenolic compounds for human
      application as chemopreventors should not be overestimated.

PMID- 7621440
TI  - Cell death regulation during multistep lymphomagenesis.
AB  - The three most common genetic abnormalities occurring in malignant lymphomas
      involve alterations resulting in the deregulated expression of the c-myc and bcl
      2 oncogenes and the inactivation of the p53 tumor suppressor gene. Relevant
      strains of genetically engineered mice, including bcl-2-Ig and E mu-myc
      transgenic mice and p53 knockout mice, have been used to prospectively examine
      the regulation of apoptotic cell death by these genes, individually and in
      combination, and their contribution to in vivo lymphomagenesis. The potential
      importance of the therapeutic induction of apoptosis is discussed.

PMID- 7621441
TI  - 5-Nitrofuran derivatives of fatty acid hydrazides induce differentiation in human
      myeloid leukaemic cell lines.
AB  - Compounds formed by 5-nitrofuran with hydrazides of formic, acetic and propionic
      acids, hereafter respectively known as SBF, SBA and SBP have been used to
      evaluate the differentiation-inducing properties on two established myeloid
      leukaemic cell lines ML-2 and EOL-1. SBP is found to be the most effective as an
      antineoplastic agent amongst the three. Induction of differentiation observed are
      in the order SBP > SBA > SBF, as assessed by morphology, NBT-reducing activity
      and surface marker antigens of the treated cells. Induction of differentiation of
      ML-2 and EOL-1 cells by the most effective compound, SBP (3 microM), is
      accompanied by perturbation of the cell cycle, with most of the cells
      accumulating in the G0-G1, phase. Inhibition of DNA synthesis occurs while
      protein and RNA synthesis remain practically unchanged.

PMID- 7621442
TI  - Chemoprotective properties of chlorophyllin against vinyl carbamate, p
      nitrophenyl vinyl ether and their electrophilic epoxides.
AB  - Chlorophyllin (CHL), a water-soluble sodium and copper derivative of chlorophyll,
      has been shown to be a strong antimutagen in several test systems, but its
      mechanism of antimutagenic action is largely unknown. In the present study, we
      have found the protective properties of CHL against vinyl carbamate, p
      nitrophenyl vinyl ether and their electrophilic epoxides. CHL exhibited dose
      related inhibition of his+ reversion in Salmonella typhimurium TA 1535 induced by
      these mutagens. Formation of DNA adducts from vinyl carbamate epoxide (VCO) and
      2'-(4-nitrophenoxy)oxirane (NPO) was also markedly attenuated in the presence of
      CHL. Oral administration of CHL prior to the topical application of each of the
      above carcinogens resulted in significant reduction in both incidence and
      multiplicity of skin tumors in mice. The effective protection by CHL against VCO
      and NPO suggest that its formation of inactive complexes with these carcinogens
      is mediated by mechanisms other than pi-pi interactions.

PMID- 7621443
TI  - Cytokine regulation of HIV-1 LTR transactivation in human hepatocellular
      carcinoma cell lines.
AB  - Human hepatocellular carcinoma (HCC) cell lines, HEP-G2, J5, and SK-HEP-1, which
      differ in their differentiation status, were compared for their trans-activating
      activities after treatment with cytokines or 12-O-tetradecanoylphorbol-13-acetate
      (TPA). These cells were transfected with a long terminal repeat (LTR) which was
      derived from human immunodeficiency virus type 1 (HIV-1) and ligated to
      chloramphenicol acetyl transferase (CAT) gene. After treatment with interleukin-1
      alpha (IL-1 alpha), interleukin-6 (IL-6), interferon-gamma (IFN-gamma), or TPA,
      they exhibited various degrees of enhancement of transactivation. The well
      differentiated HEP-G2 cells exhibited the highest degree of enhancement with
      these agents, while the poorly differentiated SK-HEP-1 cells showed no
      enhancement with cytokines and slight enhancement with TPA. The J5 cells, which
      were intermediate in their status of differentiation, showed a moderate degree of
      enhancement with cytokines and TPA. These results suggest that HCC cells at
      different stages of differentiation may produce different levels of cellular
      transacting factors activated by each of these agents. To map the cytokine
      response elements (CREs) in the HIV-1-LTR, HEP-G2 cells were transfected with
      nested series of 5' deletion mutants of HIV-1-LTR and treated with each of these
      cytokines. It was found that not only the degrees but also the patterns of
      enhancement varied depending upon the presence of positive or negative regulatory
      sequences in HIV-1-LTR, and that the NF-kappa B sequence played an important
      role, either by itself or in conjunction with the 5'-proximal response elements
      (REs) to interact with cellular trans-activating factors elicited by the cascade
      of transduction responses to cytokines. Despite the presence of promoters
      including kappa B and IFN-gamma RE as well as IL-6RE sequence in HIV-1-LTR
      transfected cells, the poorly differentiated SK-HEP-1 cells showed no enhancement
      of transactivation by these cytokines, suggesting the lack of receptors or
      activity of some signal transduction factors which are present in well
      differentiated HEP-G2 and moderately differentiated J5 cells.

PMID- 7621444
TI  - Enhancement by peptide histidine isoleucine of experimental carcinogenesis in the
      colon of rats induced by azoxymethane.
AB  - The effects of peptide histidine isoleucine (PHI) on the incidence and histology
      of colon tumors induced by azoxymethane (AOM), and on the labeling index of colon
      mucosa were investigated in Wistar rats. Rats received weekly s.c. injections of
      7.4 mg/kg body weight of AOM for 10 weeks, and of 1.0 or 4.0 nmol/kg body weight
      of PHI until the end of the experiment in week 35. Administration of PHI at the
      higher, but not the lower dosage, significantly increased the incidence of colon
      tumors. PHI had no influence on the histology of colon tumors or adenocarcinomas.
      It also caused significant increase in the labeling index of colon epithelial
      cells. These findings indicate that PHI enhances colon carcinogenesis, and that
      its effect may be related to increasing proliferation of colon epithelial cells.

PMID- 7621445
TI  - Perturbation of cell cycle kinetics in the mammary gland by stilbene estrogen,
      diethylstilbestrol (DES).
AB  - In the present study we have examined the effect of stilbene estrogen on the
      proliferative activity, cell cycle kinetics and the differentiation of the
      mammary gland of female Noble rats. The exposure of animals to stilbene estrogen
      (diethylstilbestrol) or natural estrogen (estrone) (10 micrograms/24 h)
      significantly increased proliferation in mammary epithelial cells. Both labeling
      index and growth fraction were increased by DES or estrone treatment. In
      addition, both stilbene and natural estrogen exposure altered cell cycle
      kinetics. Stilbene estrogen exposure to animals increased the conversion of
      mammary epithelial cells from G0 to G1 and G1 to S-phase cells by 8.3- and 8.5
      fold, respectively, compared to that of control. Differentiation measured by the
      degree of lobular maturation revealed that the conversion of immature structures
      to mature structures was significantly increased by 2.4-fold in response to DES
      or estrone exposure compared to that of control. Perturbation of cell cycle is
      considered as a risk factor for the development of cancer. Changes in
      proliferation and cell cycle have been shown to lead to genetic instability,
      ultimately resulting in cell transformation. Our results indicated an increase in
      labeling index and growth fraction and a perturbation in cell cycle kinetics from
      DES or estrone exposure. Perturbation of cell cycle in response to stilbene
      estrogen exposure may produce adverse effects in the mammary glands of the Noble
      rats.

PMID- 7621446
TI  - Non-destructive analysis of the protein conformational structure of human
      pituitary adenomas using reflectance FT-IR microspectroscopy.
AB  - Reflectance Fourier-transform infrared microspectroscopy was used to determine
      the secondary structure and composition of the different human pituitary
      adenomas. Non-functioning pituitary adenomas exhibited similar protein secondary
      structure and conformational composition, but active pituitary adenomas revealed
      different behavior. The differences in secondary structure for the different
      human pituitary adenomas might possibly be due to the different protein
      conformations of the proliferated adenoma tissues and various hormones shared.

PMID- 7621447
TI  - Expression of a high molecular weight form of insulin-like growth factor II in a
      Beckwith-Wiedemann syndrome associated adrenocortical adenoma.
AB  - Beckwith-Wiedemann syndrome is a rare condition (1/13,700 live births) occurring
      in both inherited and sporadic forms in the population. It is manifest as a fetal
      overgrowth syndrome, in which hypertrophy dominates the clinical picture. An
      additional complication is that these children are predisposed to a specific
      subset of childhood neoplasms, amongst which are Wilms' tumour and adrenocortical
      carcinoma. We report here the synthesis by an associated adrenal tumour of large
      quantities of a high molecular weight form of insulin-like growth factor II (IGF
      II), associated with profound suppression of circulating IGFs in the patient's
      serum. As with other tumours of this type, the tumours showed loss of material on
      chromosome 11p.

PMID- 7621448
TI  - Anti-tumour and antioxidant activity of natural curcuminoids.
AB  - Matural curcuminoids, curcumin, I, II and III isolated from turmeric (Curcuma
      longa) were compared for their cytotoxic, tumour reducing and antioxidant
      activities. Curcumin III was found to be more active than the other two as a
      cytotoxic agent and in the inhibition of Ehrlich ascites tumour in mice (ILS
      74.1%). These compounds were also checked for their antioxidant activity which
      possibly indicates their potential use as anti-promoters. The amount of
      curcuminoids (I, II and III) needed for 50% inhibition of lipid peroxidation was
      20, 14 and 11 g/m. Concentrations needed for 50% inhibition of superoxides were
      6.25, 4.25 and 1.9 micrograms/ml and those for hydroxyl radical were 2.3, 1.8 and
      1.8 micrograms/ml, respectively. The ability of these compounds to suppress the
      superoxide production by macrophages activated with phorbol-12-myristate-13
      acetate (PMA) indicated that all the three curcuminoids inhibited superoxide
      production and curcumin III produced maximum effect. These results indicate that
      curcumin III is the most active of the curcuminoids present in turmeric.
      Synthetic curcumin I and III had similar activity to natural curcumins.

PMID- 7621451
TI  - Effects of cigarette smoke and disulfiram on tumorigenicity and clastogenicity of
      ethyl carbamate in mice.
AB  - Exposure of male Balb/C mice to mainstream cigarette smoke for 4 months, starting
      10 or 30 days before the administration of ethyl carbamate (0.3% in drinking
      water for 3 weeks), resulted in an up to 57.6% (P < 0.05) decrease of lung
      adenoma multiplicity. However, the number of ethyl carbamate-induced lung tumors
      was not significantly affected by exposure to cigarette smoke when ethyl
      carbamate was injected i.p. in single doses of 0.5 or 1.0 g/kg, irrespective of
      the different treatment schedules used, i.e. (a) 10 days before and 4 days after
      the ethyl carbamate injection; (b) throughout the experiment starting 10 days
      before the ethyl carbamate injection, and (c) until the end of the experiment,
      starting 30 days after the ethyl carbamate injection. Disulfiram (500 mg/kg),
      given by gavage 24 h and 1 h before the ethyl carbamate injection, decreased by
      88.5% (P < 0.001) the multiplicity of lung adenomas but had no effect on
      tumorigenesis when administered after the carcinogen injection. Proadifen (SKF
      525 A, 50 mg/kg) injected i.p. 24 h and 1 h before and 24 h and 48 h after the
      injection with ethyl carbamate tended to decrease the multiplicity of lung
      adenomas, but not to a significant extent. Furthermore, disulfiram given 24 h and
      1 h before the i.p. administration of ethyl carbamate completely prevented its
      clastogenicity in mouse bone marrow. On the other hand, cigarette smoke, which
      was per se a weak clastogen in bone marrow erythroblasts, synergistically
      potentiated the clastogenic response to ethyl carbamate in a more than additive
      fashion.

PMID- 7621449
TI  - N-nitrosodimethylamine and 7-methylguanine DNA adducts in tissues of rats fed
      Chinese salted fish.
AB  - Previous studies have demonstrated that rats fed Chinese salted fish developed
      carcinomas of the nasopharynx and nasal cavity. In the present work the contents
      of nitrosamines in salted fish from the city of Guangzhou, southern China, and
      the contents of nitrosamines and possible nitrosamine-induced DNA adducts in
      organs of rats fed the fish were analysed. Similar levels of N
      nitrosodimethylamine (NDMA) were detected in tough and soft salted fish. The NDMA
      content in steamed fish was higher than in raw fish. In vitro incubation of
      salted fish with gastric juice significantly increased the level of NDMA. NDMA
      was found in liver and kidney from rats fed salted fish for 2 years, but no dose
      dependence was found between salted fish treatment and NDMA content. The level of
      7-methylguanine in rat liver DNA was found to be slightly higher than in DNA from
      nasopharynx. However, there were no significant differences in the level of 7
      methylguanine in DNA samples from rats fed salted fish and rats fed standard
      diet.

PMID- 7621450
TI  - Oncogene regulation of endonuclease activation in apoptosis.
AB  - Recent work has demonstrated that oncogenes and tumor suppressor proteins
      regulate apoptotic cell death. Current efforts are therefore directed at
      determining how they exert their effects. It appears that oncogenes can control
      activation of the apoptosis endonuclease(s) either by regulating the signal(s)
      that trigger the process or via effects on expression and/or activation of key
      components of the effector machinery, including the endogenous endonuclease
      itself. This article summarizes the available information on the biochemical
      mechanisms underlying the effects of oncogenes on endogenous endonuclease
      activation and presents models to explain the observation that they also regulate
      alternative cell fates such as cell proliferation and differentiation.

PMID- 7621452
TI  - Urinary excretion of sialic acid in patients with bladder tumors.
AB  - The pre- and post-treatment urinary total sialic acid/creatinine (TSA/Cr) ratios
      of patients with bladder tumor (n = 60) were determined. We found a significant
      increase in the mean urinary TSA/Cr ratio in patients with bladder tumors than in
      healthy people (99.80 +/- 15.60 micrograms/g Cr, 52.57 +/- 15.60 micrograms/g Cr,
      P < 0.001). We determined that the mean post-treatment TSA/Cr ratio of 44
      patients was significantly lower than their pretreatment ratio and this value
      also decreased to the level in healthy people. (TSA/Cr; healthy people, 52.57 +/-
      15.60 micrograms/g Cr, P < 0.001). The patients with decreased TSA/Cr ratio in
      the post-treatment period showed complete or partial regression of their disease.
      In 8 patients, urinary TSA/Cr ratio in the post-treatment period increased to 105
      +/- 14.5 micrograms/g Cr value. In clinical and pathologic evaluation, it was
      shown that disease progressed in all of these 8 patients. The mean post-treatment
      TAS/Cr ratio of 8 patients did not differ from the pretreatment ratio (87.44 +/-
      20.20 micrograms/Cr) and it was shown that their clinical status did not change.
      These findings show that urinary excretion of TSA correlates with the clinical
      status of bladder tumor and it could be used to follow the course of the disease,
      and follow-up treatment.

PMID- 7621454
TI  - Radical prostatectomy, radiotherapy or deferred treatment for localized prostate
      cancer?
AB  - Before considering the possible biases discussed above, the results as reported
      in the current literature may indicate an advantage for radical prostatectomy in
      disease specific survival at 10 years' follow-up when compared with external
      radiation therapy and deferred treatment. It appears that most of the obvious
      biases found in the literature work in favour of radical prostatectomy. The
      actual advantage of radical prostatectomy with respect to disease specific
      survival at 10 years may therefore be less than the data complications suggest.
      The magnitude of these biases is, however, impossible to assess. A probable but
      perhaps marginal benefit for the majority of the patients must, however, be put
      in relation to possible side effects and long term complications of the various
      treatments as well as the patient's preferences when choosing treatment. Reliable
      controlled data on outcome and quality of life for the various treatments of
      localized prostate cancer are needed, but we may have to wait for many years for
      such data. It must also be remembered that the results presented in this overview
      derive from a series started in the late 1970s of patients treated with the
      surgical techniques and radiotherapy technology available at that time. Today,
      the frequent use of prostate specific antigen in early detection or screening
      programmes will definitely detect a larger number of low volume prostate cancers
      that may be more curable by surgery or radiotherapy. This, however, remains to be
      proved. Moreover, new technology in radiotherapy, such as conformal therapy, may
      enable radiotherapists to deliver higher local doses of radiation to the
      prostate, which in turn may improve the cure rate for radiotherapy.

PMID- 7621453
TI  - An epidemiologist's viewpoint on screening.
AB  - Prostate cancer is an important disease causing a considerable number of new
      cases, deaths and premature loss of life each year. Three screening tests have
      been suggested: DRE, TRUS and PSA measurement in venous blood. From aggregated
      data from studies examining the performance of these tests, DRE or PSA
      measurement look the most promising with respect to their estimated detection
      rates and false positive rates (detection rate [DR] = 68%, false positive rate
      [FPR] = 5% for DRE and DR = 79%, FPR = 8% for PSA with a cut off of > 4
      micrograms/l). However, these results are tentative-more research is needed on
      the performance of these screening tests. In particular, the prevalence of
      prostate cancer in the studies was considerably higher than that expected in the
      general population and so the OAPR estimates derived are more favourable than
      predicted. A randomized controlled trial of prostate cancer screening is needed
      to know whether screening reduces mortality from this disease, although this
      would take about 10 years to perform. Current stage distribution and 5 year
      survival data suggest that if screening could increase the proportion of cancers
      diagnosed at the localized clinically inapparent stage from 23% (currently
      diagnosed) to 100%, this would represent an equivalent reduction in mortality of
      48%-about 1500 lives saved per year if screening were offered to 55-74 year old
      men. When more substantive information is available on the potential screening
      tests, it may be appropriate to conduct a randomized controlled trial. In the
      meantime, any ad hoc screening should be strongly discouraged.

PMID- 7621455
TI  - Downstaging by combination therapy with flutamide and an LHRH agonist before
      radical prostatectomy.
AB  - A total of 161 patients diagnosed as having stage B (134 patients) or C (27
      patients) prostate cancer were randomly assigned to radical prostatectomy alone
      or to 3 months of neoadjuvant combination therapy with the anti-androgen
      flutamide and an LHRH agonist before radical prostatectomy. Neoadjuvant
      combination therapy before radical prostatectomy decreased cancer positive
      surgical margins from 33.8% in the control group to only 7.8%, thus leaving 92.2%
      of patients with negative margins at surgery for a 39.2% increase in specimen
      confined disease. Although on average the final stage determined at
      histopathological examination of the surgical specimen was more advanced than
      predicted at initial diagnosis in 33.8% of control patients, an opposite
      observation was made in the group of men who received the 3 month neoadjuvant
      combination therapy where the final stage, instead of being more advanced, was
      less advanced than at diagnosis in an average of 21.1% of men for a net 54.9%
      improvement of staging in favour of combination therapy. On the other hand, organ
      confined disease increased from 49.3% to 77.8% of patients after 3 months of
      combination therapy, for a 57.9% increase in the incidence of organ confined
      disease. Although long term follow up of these patients is required to determine
      the impact on survival, the marked influence of neoadjuvant combination therapy
      on the stage of the disease suggests the possibility of a major improvement in
      the morbidity and mortality from prostate cancer.

PMID- 7621456
TI  - Hormone therapy: an overview.
AB  - Hormonal treatment of prostate cancer has advanced little in the past 20 years.
      Total androgen ablation may offer a 20% survival advantage when compared with
      monotherapy, as might the use of stilboestrol if its cardiovascular side-effects
      could be abolished with aspirin or some other agent. Neither approach, however,
      is likely to lead to a cure. Currently available cytotoxic chemotherapy appears
      to offer little survival advantage. There is an urgent need for the development
      of other treatments.

PMID- 7621457
TI  - Molecular biology of prostate cancer progression.
AB  - A number of genetic changes have been documented in prostate cancer, ranging from
      allelic loss to point mutations and changes in DNA methylation patterns
      (summarized in Fig. 1). The most consistent changes seen are those of allelic
      loss events, with the majority of tumours examined showing loss of alleles from
      at least one chromosomal arm. The short arm of chromosome 8, followed by the long
      arm of chromosome 16, seem to be the most frequent regions of loss, suggesting
      the presence of novel tumour suppressor genes. Deletions of one copy of the RB
      and TP53 genes are less frequent as are mutations of the TP53 gene, and
      accumulating evidence suggests the presence of an additional tumour suppressor
      gene on chromosome 17p, which is frequently inactivated in prostate cancer.
      Alterations in the E-cadherin/alpha catenin mediated cell-cell adhesion mechanism
      appear to be present in almost half of all prostate cancers and may be critical
      to the acquisition of metastatic potential of aggressive prostate cancers.
      Finally, altered DNA methylation patterns have been found in the majority of
      prostate cancers examined, suggesting widespread alterations in methylation
      modulated gene expression. The presence of multiple changes in these tumours is
      consistent with the multistep nature of the transformation process. Finally,
      efforts to identify prostate cancer susceptibility loci are under way, which may
      elucidate critical early events in prostatic carcinogenesis.

PMID- 7621458
TI  - Intermittent endocrine therapy and its potential for chemoprevention of prostate
      cancer.
AB  - This chapter has reviewed the limitations of the use of chemotherapy in patients
      with hormone resistant prostate cancer. Although demonstrating that there is a
      small number of patients with very chemosensitive tumours, the age profile and
      intolerance to chemotherapy make it highly unlikely that this modality of
      treatment will be used more routinely despite the increasing evidence that the
      slow decline of prostate specific antigen with endocrine treatment can be used
      early to select patients who might respond to chemotherapy. Equally certain is
      that it will not be of use for chemoprevention of the early stages of this
      disease. Although some data suggest that tumours that respond rapidly and
      completely to endocrine therapy may benefit from the use of non-specific
      immunotherapy, there is no evidence that any form of vaccination therapy would be
      of value in preventing the disease in the main because all attempts to find
      evidence of a virus, particularly a human papillomavirus subtype, involved in its
      aetiology have proved negative. The discovery that standard endocrine therapy
      induces thymic regeneration and peripheral blood lymphocytosis, taken together
      with the demonstration that surgical trauma induced by a needle biopsy could
      accelerate tumour dissemination because of tumour activation by trauma induced
      release of tissue repair cytokines, has led to the proposal that short term
      endocrine treatment should be given to all prostate specific antigen positive
      patients prior to needle biopsy. New information on the slow kinetics of prostate
      cancer growth, with cancers detected by screening being found up to 20 years
      before clinical presentation and more than 80% of early tumours failing to double
      the prostate specific antigen level within 2 years, has led to proposals for a
      new strategy for endocrine chemoprevention of prostate cancer. This has in part
      been encouraged by greater confidence in the use of intermittent hormone therapy
      to treat patients with metastatic disease. These observations have led to the
      suggestion that it might be possible to prevent deaths by treating early cases
      detected from prostate specific antigen screening with short term (1-3 months)
      endocrine treatment every 5 to 10 years.

PMID- 7621459
TI  - Strontium-89 in the management of metastatic prostate cancer.
AB  - Strontium-89 is a beta emitting radioisotope, avidly taken up by osteoblastic
      metastatic prostatic cancer. In both open and controlled studies, it has been
      shown to palliate metastatic pain effectively. It is as effective as conventional
      radiotherapy in palliation of the primary site(s) of pain, but in addition, it
      seems to delay pain progression. Its role is confined to palliation of pain in
      the absence of actual or impending complications (cord compression or
      pathological fractures). Bone marrow suppression makes it unsuitable for
      myelosuppressed patients. Cost is the main limitation to its use. It is a useful
      alternative to hemibody radiotherapy and to local treatment in selected patients.
      Its use in other tumour types (especially breast cancer) is currently under
      investigation. Trials investigating its use to delay onset of pain in symptom
      free relapsing patients should be considered.

PMID- 7621461
TI  - American studies on suramin therapy in hormone resistant prostate cancer.

PMID- 7621462
TI  - Multiple primary cancers in association with prostate cancer.
AB  - Patients with prostate cancer are at a significant risk of either having a
      preceding tumour or developing a second malignancy. The precise mechanism by
      which second cancers develop is not clear but may be the result of exposure to a
      shared mutagen, abnormalities in oncogene activation or the aberrant expression
      of tumour suppressor genes. In the recent past, case reports and tumour registry
      studies on the risk of second cancer development have been important and have
      alerted the clinician that careful surveillance in this group of patients is
      required. More prospective hospital based studies are required to delineate the
      true risk of second malignancies in association with prostate cancer.

PMID- 7621463
TI  - The geography of prostate cancer and its treatment in Japan.
AB  - The age adjusted death rate from prostate cancer in Japan is one of the lowest in
      the world but is rising steadily. The vast majority of cases of prostate cancer
      remain undetected during life, the prevalence of prostate cancer detected at
      autopsy being 2800 times that of lethal cancer in Japanese in Japan, 570 times in
      whites in the USA and 470 times in blacks in the USA. A case-control study of
      prostate cancer carried out in Japan and the Netherlands revealed a number of
      statistically significant risk factors, including rural residence, more brothers,
      colon neoplasms in relatives, no morning erections, frequent sexual intercourse
      in 30s, episodes of sexually transmitted disease, lower plasma testosterone and
      dihydrotestosterone concentrations and lower beta-carotene intake.

PMID- 7621460
TI  - UK studies on suramin therapy in hormone resistant prostate cancer.
AB  - New insights regarding the biology of hormone resistant CaP have shown that major
      growth factors other than testosterone are responsible for cellular proliferation
      of androgen resistant prostate cancer cells. In vitro studies have confirmed the
      efficacy of growth factor inhibitors such as suramin in reducing cellular
      proliferation of androgen dependent LNCaP and independent PC-3 CaP cell lines as
      well as CaP cells obtained by primary culture. Initial clinical trials using high
      dose suramin (peak serum concentration 250-300 micrograms/ml) as monotherapy in
      patients with hormone resistant CaP have shown some promise, but the duration of
      response to therapy has been short lived and suramin toxicity is a problem. To
      minimize toxicity without reducing anti-tumour activity, studies evaluating its
      use in combination with other cytotoxic drugs are attractive in CaP. Suramin and
      doxorubicin, tumour necrosis factor and EMP have shown synergy in vitro. However,
      in a phase II clinical trial using combination therapy with low dose suramin (140
      micrograms/ml) and mitomycin C in 32 patients, there was one complete response
      and six partial responses, and in 15 patients, the disease had stabilized. The
      median time to treatment failure was 103 days, and the median survival was 209
      days. This regimen caused significant toxicities. The present study has shown
      that the combination of EMP 280 mg twice a day and suramin 1 g weekly infusions
      for 6 weeks, compared to EMP 280 mg alone, showed a statistically significant
      difference in the rate of depression of PSA levels after 3 and 6 months of
      treatment (p < 0.01) and a statistically significant reduction in bone pain and
      requirement for analgesics in patients on combination therapy-100% compared to 0%
      for patients on EMP alone.

PMID- 7621464
TI  - The geography of prostate cancer and its treatment in Africa.
AB  - Cancer of the prostate is perhaps the commonest urological malignancy affecting
      Africans. The incidence between different countries varies and mirrors very
      closely the socioeconomic status of the countries and the life expectancy. The
      disease has an early peak incidence at ages 55-64 years, compared to 65-74 years
      for whites. This is primarily due to the low life expectancy in Africans. Late
      presentation is a common feature in Africans. Stilboestrol is widely used in
      treating disseminated cancer of the prostate not only because it is cheap and
      effective, but also because the cardiovascular side effects of stilboestrol seem
      not to be serious in Africans compared to whites. Further study of cancer of the
      prostate gland in indigenous Africans should provide vital data on the
      epidemiology and aetiology of this important cancer and may shed light on why the
      clinical aggressiveness of the disease varies from one part of the world to
      another.

PMID- 7621465
TI  - The geography of prostate cancer and its treatment in Israel.

PMID- 7621466
TI  - The geography of prostate cancer and its treatment in Europe.
AB  - The search for more efficient treatments for prostate cancer continues. In
      localized prostate cancer, the combination of neo-adjuvant or adjuvant hormone
      therapy with surgery may improve curability rates. In the palliation of advanced
      prostate cancer, novel concepts of varying forms of maximal androgen blockade,
      including the re-introduction of safer forms of oestrogen therapy, should be
      capable of lengthening the time to progression and improving the quality of life
      of patients with advanced disease. The chemotherapy of prostate cancer remains
      experimental, but its earlier introduction may enable better dosing schedules to
      further limit advanced disease.

PMID- 7621467
TI  - A basic science perspective.

PMID- 7621468
TI  - An historical perspective of the pathology and treatment.
AB  - There are inner and outer gland groups in the human prostate. Benign nodular
      hyperplasia develops from the inner group of glands. Carcinomas arise in the
      outer glands and spread beyond the prostate at an early stage in the disease. The
      biological malignancy of prostatic cancer varies from patient to patient and from
      part to part of the same tumour. Some tumours remain biologically inactive or
      latent so that there must be some naturally occurring mechanism that controls
      tumour growth in some cases. This phenomenon is not confined to the prostate but
      can be found in many other organs, although not so frequently. It may represent a
      stage in tumour progression or reflect the balance between growth stimulating and
      inhibiting factors (Franks, 1956b). Our new knowledge of these factors suggests
      that this may be an area well worth looking at again. Prostatic cancer patients
      may be divided into groups that differ in their response to endocrine treatment.
      These differences may be due to changes in the tumour cells or in the host. A
      temporary state of tumour retardation or latency follows endocrine treatment in
      about 70-80% of all cases, but whatever form of treatment is used, about 75% of
      all patients die within 3 years. Even in tumours that show a marked response,
      endocrine treatment does not destroy all the tumour cells. Hormone sensitivity is
      not a property of the tumour as a whole but may vary from part to part of the
      same tumour.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7621469
TI  - A physician's perspective.

PMID- 7621470
TI  - Surgery from a UK perspective.

PMID- 7621471
TI  - Surgery from a US perspective.
AB  - Prostate screening has made it possible to detect organ confined prostate
      carcinoma in men with a life expectancy of 20 years and longer. These clinically
      significant malignancies may be successfully eradicated by means of anatomical
      dissection of the prostate, which minimizes both morbidity and mortality. In a
      retrospective series of patients with clinically localized prostate cancer who
      were treated with a radical retropubic prostatectomy and lymph node dissection, 5
      and 10 year crude survival rates were 96% and 86%. Survival was compromised by
      penetration of tumour through the prostatic capsule, and even more significantly
      by involvement of the seminal vesicles. The use of prostate specific antigen
      (PSA) concentrations to monitor disease progression before any clinical
      manifestation revealed that disease free survival was less than previously
      reported. Patients diagnosed and treated more recently had longer disease free
      survival than the overall group mainly because of earlier detection with PSA,
      with consequent lower tumour volumes and stage. In addition, 92 +/- 3(SD)%
      patients with pathologically organ confined tumours, without capsular or seminal
      vesicle invasion, are clinically disease free with non-detectable PSA at 5 years.
      Our data therefore show that radical prostatectomy can cure patients with organ
      confined prostate cancer, with acceptable morbidity. Although the need for cure
      may be questioned in many patients, young patients with prostate cancer almost
      certainly benefit from eradication of the malignancy.

PMID- 7621472
TI  - The role of stromal-epithelial interaction in normal and malignant growth.
AB  - Stromal-epithelial interaction has a fundamental role in determining normal
      prostate development. Aberrant interaction between stroma and epithelium in the
      prostate is thought to contribute to neoplastic progression. Using a cell-cell
      interaction model, we observed that an inductive fibroblast cell line derived
      from fetal urogenital sinuses can confer growth responsiveness to androgen in
      both prostate and non-prostate epithelial cells in vivo. This concept was applied
      to test whether inductive stromal cells from bone or prostate alter cancer growth
      and metastasis. We observed that when a non-tumorigenic stromal cell line derived
      from a human osteosarcoma interacted with a non-tumorigenic androgen dependent
      prostate cancer cell line (LNCaP) in vivo, there was a marked alteration of both
      genotypes and phenotypes of the subsequently derived LNCaP sublines. One such
      subline, C4-2, acquired androgen independence as well as osseous-metastatic
      potential. These results support the concept that "genomic adaptation" is the
      most likely mechanism to explain the phenomenon of prostate cancer cell lines
      being permanently altered as a result of stromal-epithelial interaction in vivo.
      The establishment and further refinement of this cell-cell interaction model will
      allow us to define the roles of growth factors, growth factor receptors and
      extracellular matrices in prostate carcinogenesis. This approach could lead to
      the development of new therapeutic modalities that influence the rate of human
      prostate cancer progression.

PMID- 7621473
TI  - Endocrine control of prostate cancer.
AB  - Steroid hormones play an important part in prostate biology. Androgens are
      crucial for the normal development of the prostate gland and in maintaining its
      functional state in the adult. It seems that the prolonged presence of androgens
      might also be an important factor in the development of prostate cancer. In
      addition, androgens and oestrogens appear to play a part in the development of
      benign prostatic hypertrophy, although the exact nature of their role has not
      been clearly defined. Stimulation of prostate cancer growth by androgens is well
      established with androgen withdrawal therapy being the most effective therapy in
      men with prostate cancer. Additive steroid therapy of metastatic prostate cancer
      with oestrogens or progestogens has also proved effective. The effects of
      androgens on prostate cancer cell growth might be mediated through modulation of
      growth factor expression and alteration of growth factor receptor levels.
      Androgen response can be modulated by the expression of mutated oncogenes such as
      ras. Androgen independence can occur through a loss of AR expression or mutation
      of the AR; however, the patterns of AR expression in normal prostatic tissue from
      development to adulthood and in cancer are now just beginning to be described.
      Other steroids, such as the retinoids, show promise as preventive agents,
      possibly through the modulation of growth factors. Vitamin D compounds modulate
      prostate cancer cell growth, but their role in prevention and therapy is unclear.

PMID- 7621475
TI  - The pathology of incidental carcinoma.
AB  - "Incidental" cancer refers to predominantly well differentiated cancer that
      arises in the transition zone and is found by chance in TURP chips. These tumours
      are frequently small and may be completely resected by TURP, although a
      significant number have an additional tumour that is unreachable with a
      resectoscope. These tumours often co-exist with benign prostatic hyperplasia.
      Putative precursors of incidental carcinoma include high grade PIN and AAH, and
      these lesions are frequently found in the transition zone in prostatectomies for
      cancer. The single most significant question in treating incidental
      adenocarcinoma is how to separate tumours that will progress from those that will
      not progress during the expected lifetime of the patient. The 1992 revision of
      the TNM staging system separated non-aggressive (T1a) and aggressive (T1b)
      incidental cancer according to the number of foci of cancer, using more than
      three foci as the cutpoint to identify more aggressive cancer. However, 8-37% of
      patients with T1 a cancer will develop cancer progression within 10 years if
      untreated, with the risk of progression increasing with additional years of
      follow-up. Important prognostic factors include the patient's age, tumour
      location (peripheral zone v. transition zone), tumour grade, tumour volume, serum
      PSA concentrations and morphometric factors such as nuclear roundness. Studies
      directed at early detection allow discovery of increasingly smaller cancers.

PMID- 7621474
TI  - Risk factors for prostate cancer.
AB  - The risk for prostate cancer increases with age, with a family history of the
      disease and with living in a Westernized society, especially for blacks. Although
      there is no doubt that genetic factors are important, and might explain some of
      the geographical variation in rates, the differences between populations are so
      large that environmental factors must also be important. The evidence suggesting
      that dietary fat and/or meat may increase risk is quite consistent. The observed
      relative risks are small (about a 30% increase for high v. low consumption) but
      may have been underestimated because of inaccurate measurement of diet and
      further study of this topic is needed. The evidence does not support the
      hypothesis that carotene intake is associated with risk. There is reasonably
      consistent evidence suggesting that an increased risk for prostate cancer is
      associated with a high level of sexual activity and/or a history of sexually
      transmitted disease, and with vasectomy. These observations need further
      investigation to eliminate the possibility that they are due to biases. Much more
      information is needed. Prospective studies, with dietary and lifestyle
      questionnaires and stored blood samples, are needed to answer the outstanding
      questions.

PMID- 7621476
TI  - Geographical epidemiology of prostate cancer: is there an association with
      infection?
AB  - Incidence and mortality data from the 1960s, when screening for cancers of the
      cervix and prostate was minimal, reveal a positive but statistically
      nonsignificant geographical association between the two diseases. Data on cancer
      incidence from African cancer registries and from the South African National
      Cancer Registry also show weak but positive associations. To determine whether
      infection is a cause of prostate cancer, case-control studies need to be
      conducted on individuals with and without prostate cancer or prostate cancer
      precursors. The screening of serum for prostate specific antigen provides an
      excellent opportunity to test for sexually transmitted agents.

PMID- 7621477
TI  - Human papillomavirus infection of the prostate.
AB  - Seven studies that have reported on the prevalence of anogenital types of the
      human papillomavirus in prostate cancer, benign prostatic hypertrophy and normal
      prostatic tissue are reviewed. When the data were combined, 32% of the cancers
      were positive, compared to 49% of the benign lesions and 9% of the normal tissue.
      The highest positivity rates were found in the earlier studies, and the more
      recent results have been more negative. The finding of higher rates in benign
      compared to malignant tissue and the failure of confirmatory studies to support
      earlier reports make it unlikely that the common anogenital papillomaviruses have
      an important role in prostate carcinogenesis. More work is needed to decide if
      the prostate is a significant reservoir for the papillomavirus in the male.

PMID- 7621478
TI  - Is there a reasonable differential indication for different hydrocephalus shunt
      systems?
AB  - We tested various shunt systems for pressure/flow characteristics and long-term
      reliability. In addition, we used a model to simulate activities of daily life
      postural changes, blood and airway pressure changes and their impact on CSF
      pressure and flow through various ventriculo-peritoneal shunt systems. In the
      recumbent position, the changes in flow rate and CSF pressure depended on the
      valve resistance. Various valves showed deviations from the pressure/flow
      characteristics claimed for them and proved to be unreliable during long-term
      perfusion. The flow rate increased in the head-up position. Negative intracranial
      CSF pressure was due to the continued flow through the shunt system afforded by
      the siphon effect. The siphon effect was so marked in the upright position that
      valves of various kinds and with various resistances did not make any significant
      difference in the resulting intracranial pressure (ICP). The shunt systems,
      however, differed in the maximum flow rate in the upright position, leading to a
      different steep fall in ICP following elevation of the body. Ball-and-spring
      valves had the highest flow rates (> 500 ml/h), leading to negative ICP within
      seconds. Diaphragm valves, and especially the self-adjusting diaphragm valve,
      demonstrated a slower drop in ICP, taking several minutes to reach negative ICP.
      ASD and SCD, however, did prevent any siphoning effects, leading to an ICP within
      the corresponding valve opening/closing pressure range. Our results demonstrate
      that in most patients there is no significant difference in various different
      shunting systems as long as the patient is mobile.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7621479
TI  - Overdrainage and shunt technology. A critical comparison of programmable,
      hydrostatic and variable-resistance valves and flow-reducing devices.
AB  - When vertical body position is simulated, conventional differential pressure
      valves show an absolutely unphysiological flow, which is 2-170 times the normal
      liquor production rate. Although this is compensated in part by the resistance of
      the silicon tubes, which may produce up to 94% of the resistance of the complete
      shunt system, a negative intracranial pressure (ICP) of up to 30-44 cmH2O is an
      unavoidable consequence, which can be followed by subdural hematomas, slit
      ventricles, and other well-known complications. Modern shunt technology offers
      programmable, hydrostatic, and "flow-controlled" valves and anti-siphon devices;
      we have tested 13 different designs from 7 manufacturers (56 specimens), using
      the "Heidelberg Valve Test Inventory" with 16 subtests. "Programmable" valves
      reduce, but cannot exclude, unphysiological flow rates: even in the highest
      position and in combination with a standard catheter typical programmable Medos
      Hakim valves allow a flow of 93-232 ml/h, Sophy SU-8-valves 86-168 ml/h with 30
      cmH2O. The effect of hydrostatic valves (Hakim-Lumbar, Chhabra) can be
      inactivated by movements of daily life. The weight of the metal balls in most
      valves was too low for adequate flow reduction. Antisiphon devices are highly
      dependent on external, i.e. subcutaneous, pressure which has unpredictable
      influences on shunt function, and clinically is sometimes followed by shunt
      insufficiency. Two new Orbis-Sigma valves showed relatively physiological flow
      rates even when the vertical position (30 cmH2O) was simulated. One showed an
      insufficient flow (5.7 ml/h), and one was primarily obstructed. These have by far
      the smallest outlet of all valves. Additionally, the ruby pin tends to stick.
      Therefore, a high susceptibility to obliterations and blockade is unavoidable.
      Encouraging results obtained in pediatric patients contrast with disappointing
      experiences in some German and Swedish hospitals, which suggests that our
      laboratory findings are confirmed by clinical results. The concept of strict flow
      limitation seems to be inadaequate for adult patients, who need a relatively high
      flow during (nocturnal) ICP crises. The problem of shunt overdrainage remains
      unsolved.

PMID- 7621480
TI  - CSF shunt physics: factors influencing inshunt CSF flow.
AB  - Cerebrospinal fluid (CSF) in a shunt does not have a constant flow rate. The flow
      fluctuates from 0.01 ml/min to 1.93 ml/min according to each patient's own daily
      supine rhythmic pattern. We determined and evaluated the factors influencing CSF
      flow in a shunt in 19 cases of hydrocephalus. Postural changes, such as head
      elevation, led to increases by over 0.04 ml/min in inshunt CSF flow, while
      inshunt CSF flow in the supine position was less than 0.04 ml/min. Respiratory
      changes, such as coughing and apnea-hyperventilation, also influenced inshunt CSF
      flow. Changes in intracranial pressure (ICP) corresponded to changes in inshunt
      CSF flow. Inshunt CSF flows were higher than average during the night, the flows
      being stimulated by increases in ICP especially during REM sleep.

PMID- 7621481
TI  - Non-invasive ICP monitoring in infants: the Rotterdam Teletransducer revisited.
AB  - Measurement of intracranial pressure (ICP) is important in patients at risk of
      raised ICP, as in hydrocephalus. Ideally, it should be non-invasive, thus
      avoiding the risk of infection and other complications: Such is provided by
      measurement of ICP through the anterior fontanelle. There are several methods of
      measuring anterior fontanelle pressure (AFP); those most frequently used are
      based on the applanation principle. An evaluation of AFP measurement devices
      resulted in the choice of the Rotterdam Teletransducer (RTT) to be used in our
      study of children with hydrocephalus. The literature contains little information
      on the accuracy or validation of the AFP measurements using the RTT. Therefore,
      the physical qualities of the RTT were reassessed, using a specially developed
      calibration device. The results of this study demonstrate that membrane
      temperature does not have any effect on the measured pressure. The thermal
      stabilization time of the RTT was found to be 3 h after switching on.
      Insufficient thermal stabilization results in a pressure underestimation of up to
      3 mmHg. Furthermore, a maximum inaccuracy of 2.6 mmHg, after calibration and
      readjustment of the transducer, was calculated. Validation of the equipment was
      achieved by simultaneous AFP/ICP measurements in hydrocephalic patients showing
      high correlations (r = 0.96-0.98). The discussion suggests a measurement protocol
      as a means of increasing the reliability of RTT measurements.

PMID- 7621482
TI  - Cerebral hemodynamics and "re-build-up" phenomenon on electroencephalogram in
      children with moyamoya disease.
AB  - "Re-build-up" phenomenon, induced by hyperventilation, is a characteristic
      finding on electroencephalogram (EEG) in children with moyamoya disease, and
      suggests close correlation with cerebral ischemic attack. Its mechanism, however,
      remains obscure. In this study, we examined the relationship between the cerebral
      hemodynamics and this phenomenon before and after vascular reconstructive
      surgery. Regional cerebral blood flow and its reactivity to acetazolamide were
      analyzed using the xenon-133 inhalation method and single photon emission
      computed tomography in six children with moyamoya disease. These results were
      compared with the EEG. Regional vasoreactivity to acetazolamide was significantly
      lower in "re-build-up" -positive regions than in "re-build-up" -negative regions.
      Postoperative studies revealed a significant improvement of reactivity in the
      regions where the "re-build-up" phenomenon disappeared after surgery. These
      results suggest that the "re-build-up" phenomenon represents a focal reduction of
      the cerebral perfusion reserve in moyamoya disease.

PMID- 7621483
TI  - Infantile hydrocephalus: management using CT assessment.
AB  - When determining a management plan for infantile hydrocephalus, the determining
      factor for or against the implantation of a shunt is the degree of ventricular
      dilatation. The author has devised a standardised method of estimating this, the
      use of which has been shown to achieve consistently successful results.
      Dilatation was determined using the ventricular/biparietal (V/BP) ratio from the
      axial CT scan at the mid-portion of the bodies of the lateral ventricles, showing
      the greatest ventricular dilatation. According to this method, hydrocephalus was
      classified into four grades. These were mild (V/BP ratio 0.26-0.40), moderate
      (V/BP ratio 0.41-0.60), severe (V/BP ratio 0.61-0.90) and extreme (V/BP ratio
      0.91-1). A V/BP ratio of less than 0.26 was considered normal. This method
      appeared to be accurate and reproducible in infants with hydrocephalus including
      those with asymmetrical and multiloculated ventricular dilatation. In all the
      patients with mild hydrocephalus, spontaneous regression or stabilisation
      occurred and their developmental outcome was normal. Patients with moderate and
      severe hydrocephalus needed a ventricular shunt and the developmental outcome was
      satisfactory in 87% of the cases. They were functionally normal although 18 had
      some abnormal neurological signs. In patients with extreme hydrocephalus the
      developmental outcome following shunting was satisfactory in 31% of the cases.
      They were functionally normal although four had abnormal neurological signs. This
      plan of management was used in a total of 144 infants and it proved to be highly
      successful.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7621484
TI  - Characteristics of cerebrospinal fluid circulation in infants as detected with MR
      velocity imaging.
AB  - Analysis of cerebrospinal fluid (CSF) flow and motion at the craniospinal
      junction was conducted by magnetic resonance velocity imaging with phase encoding
      followed by motion velocity integration. Thirteen normal subjects classified into
      two groups were studied: an infant group with open sutures and fontanel, and a
      noninfant group with closed sutures and fontanel. Predominance in CSF to-and-fro
      motion was recognized in the ventral subarachnoid space, and a maximum caudad
      motion velocity of 7.5 +/- 2.4 mm/s was recorded in the infant group and one of
      14.9 +/- 6.2 mm/s in the noninfant group. The average bulk flow velocity in all
      cases was 86.7 +/- 81.6 (means +/- SD) mm/min. The difference in flow velocity
      between the infant group (19.7 +/- 28.2 mm/min) and the noninfant group (116.5 +/
      80 mm/min) suggested that the CSF circulation around the cervical spine may vary
      at different ages.

PMID- 7621485
TI  - Nongalenic cerebral arteriovenous malformations in neonates and infants. Review
      of 26 consecutive cases (1982-1992).
AB  - We present 26 consecutive cases of nongalenic pial arteriovenous malformations
      (PAVMs) diagnosed in the neonatal period or in infancy. No diagnosis was made
      antenatally. Presenting symptoms in neonates were systemic cardiac manifestations
      (54%), seizures (31%), and hemorrhages (15%). In infants, hemorrhagic strokes and
      hydrodynamic disorders (external or internal hydrocephaly, macrocephaly, atrophy)
      both occurred in 38% of cases. Systemic cardiac manifestations and seizures were
      rare at that age (respectively 16% and 8%). Sixty-two percent of neonates and 31%
      of infants already had neurocognitive disorders (assessed by pediatric
      neurocognitive testing: Brunet-Leizine and Denver tests) when referred. The
      venous drainage and its anomalies (ectasias, stenoses, thromboses) were the main
      causes of symptoms. Atrophy and leukomalacic lesions occurred rapidly; they
      express local hydrovenous disorders and are specific to this population group.
      Untreated neonates and infants have a poor prognosis. Endovascular treatment,
      although partial and challenging in all instances, represents the treatment of
      choice in our series. Of the eight neonates treated, one improved to normal
      (12.5%), while four remained stable (50%): two neurologically normal, two with
      mild neurological deficit. Three (37%) died despite embolization (heart failure,
      multiorgan failure, postoperative death). Transient neurological complications
      occurred in two cases (25%): hemiparesis in one patient with a rolandic and in
      one with a thalamic AVM. Of the eight infants successfully embolized, one was
      significantly improved (12.5%) and is now neurologically normal, while five
      remained stable (62.5%): four neurologically normal, one with mild neurological
      deficit. One died between two sessions of embolization from intracerebral
      hemorrhage (12.5%). Hemianopsy occurred in one case (12.5%) after embolization of
      an occipital AVM. In one additional case in a normal child we failed to embolize
      the last small pial AVM of four after the three others had spontaneously
      thrombosed. With a minimal follow-up of 18 months and a maximum of 7 years, the
      review of our series shows 53% of the initial group of neonates and infants
      growing neurologically normal after therapeutic management in our institution;
      23.5% died despite treatment, and the remaining 23.5% present minor neurological
      deficit. When targeted at the points of angioarchitectural weakness, embolization
      contributes to stabilizing a lesion. It should be undertaken rapidly to avoid
      loss of brain substance secondary to hemorrhage, atrophy, or leukomalacia, and to
      allow neurocognitive recovery and normal brain maturation. In our experience,
      these lesions are the most aggressive ones for the maturing brain, and the most
      difficult to approach technically. They represent a new therapeutic field and
      have their own specific anatomy and physiology.

PMID- 7621486
TI  - Cranial fasciitis with massive intracranial extension.
AB  - The case of a 10-month-old boy with cranial fasciitis is described. The patient
      had a rapidly growing subcutaneous mass in the left frontotemporal region.
      Computed tomography and magnetic resonance imaging clearly demonstrated a mass in
      the left temporoparietal bone extending both intra- and extracranially. The tumor
      seemed to originate from the calvarium, being located between the periosteum and
      the dura mater. Total resection of the tumor was performed, and the tumor was
      histologically identified as cranial fasciitis. A brief review of the literature
      is included that emphasizes the need for further investigation of this benign
      lesion that is frequently confused with a malignant neoplasm.

PMID- 7621487
TI  - Multiple pineal cysts associated with an ependymal cyst presenting with infantile
      spasm.
AB  - We present a unique case of infantile spasm in a patient with multiple pineal
      cysts associated with an ependymal cyst. Such a morphological etiology, to our
      knowledge, has not been described for patients with infantile spasm. Although
      postoperative neuroradiological studies demonstrated satisfactory surgical
      results, the patient continued to have seizures.

PMID- 7621488
TI  - Successful chemoradiation therapy for high-grade skull base chondrosarcoma in a
      child.
AB  - High-grade chondrosarcoma in the skull base has been known to be extremely
      refractory to adjuvant therapy. We report successful chemoradiation therapy for
      skull base chondrosarcoma in a child. The patient was a 6-year-old boy with an
      invasive skull base tumor. In spite of gross total removal of the tumor, it
      recurred 1 month after surgery. Following an intra-arterial injection of
      adriamycin (10 mg), the second gross total removal was carried out. At the end of
      the operation, cisplatin (20 mg) was locally injected into the surgical cavity.
      The patient was further given a total of six courses of systemic chemotherapy in
      combination with adriamycin (30 mg/m2) and cisplatin (100 mg/m2) and 55 Gy focal
      irradiation. One year after the most recent surgery, the patient is in complete
      remission. The efficacy of adjuvant therapy of this rare tumor is discussed.

PMID- 7621489
TI  - A 30-month study investigating the effect of adding triclosan/copolymer to a
      fluoride dentifrice.
AB  - The aims of the study were (1) to compare the anticaries efficacy of a silica
      abrasive dentifrice containing 0.24% NaF and 0.3% triclosan/2.0% copolymer with a
      similar dentifrice without the triclosan/copolymer and (2) to study any
      disturbance of the oral mucosa associated with the test formulation. A double
      blind, random, unsupervised, 30-month longitudinal clinical trial was conducted
      on 3,462 children who were initially 11-13 years of age. Two trained and
      calibrated dentists each examined approximately half the children. Examinations
      were undertaken at baseline, 15 months and 30 months. No significant differences
      were found between the DFS or DFT mean increments for the two dentifrice groups
      after 15 or 30 months. At 30 months the 90% confidence interval for the ratio of
      the mean increments satisfied the ADA criteria for equivalence. It is concluded
      that a 0.24% NaF/silica abrasive dentifrice containing 0.3% triclosan/2.0%
      copolymer is equivalent in its anticaries efficacy to a similar dentifrice
      without the addition of triclosan/copolymer. No side effects attributable to the
      test or control dentifrices were observed at any time during the study.

PMID- 7621490
TI  - Anticaries effect of different amine fluoride concentrations in schoolchildren.
AB  - A double-blind 3-year clinical trial was conducted in a nonfluoridated water
      community in which 354 schoolchildren aged 9-10 years were assigned randomly to
      three groups (A, B and C) and subjected to a treatment with 1 of 3 different
      concentrations of amine fluoride solution every 2 months. Clinical examinations
      were conducted at baseline and after 1, 2, and 3 years. For group A (positive
      control) receiving topical applications of amine fluoride solution (1%), the 3
      year DMFT and DMFS increments were 4.0 +/- (SD) 2.7 and 8.5 +/- 5.6,
      respectively. For group B (0.5% F), the DMFT and DMFS increments were 4.4 +/- 3.0
      and 8.4 +/- 5.7, respectively; these differences being statistically not
      significant. The mean caries increments in group C (0.25% F) were 5.1 +/- 2.9 for
      DMFT and 10.0 +/- 5.5 for DMFS. The differences in incremental caries scores
      between group C and groups A or B were statistically significant (p < 0.05).
      Thus, the amine fluoride solution, in which the fluoride content was reduced by
      half, provided similar caries reductions in schoolchildren as did a standard
      amine fluoride solution with 1.0% F.

PMID- 7621491
TI  - Effect of urea in sugar-free chewing gums on pH recovery in human dental plaque
      evaluated with three different methods.
AB  - The aim of this investigation was to study the effect of sugar-free chewing gums
      containing various amounts of urea on the pH recovery in dental plaque. Three
      plaque-measuring methods were used, i.e., the telemetric, the microtouch, and the
      sampling methods. The subjects who had refrained from toothbrushing for 3-7 days
      rinsed with either 10 or 50% (w/v) sucrose solutions and then chewed for 10 min:
      (1) one piece of chewing gum in a series of six tests in which the urea content
      increased from 10 to 80 mg per piece of gum: (2) one or two pieces of gum
      containing 20 mg urea, and (3) one, two, or three pieces of gum, one after the
      other, containing 20 mg urea. In some of the test series, a conventional
      sugarless gum was used as a control. A quick rise in plaque pH was found with all
      urea-containing chewing gums within the first minutes of chewing, and
      neutralization continued during the whole 10-min chewing periods. Higher
      concentrations of urea resulted in more pronounced pH recovery. Slightly higher
      plaque pH values were found when chewing on two pieces at a time of a 20-mg urea
      gum was compared with only one piece. Significantly higher pH values were
      recorded when using three pieces of chewing gum, one after the other (10 + 10 +
      10 min), as compared with two pieces (10 + 10 min) or just one piece (10 min). In
      conclusion, all sugar-free chewing gums tested, particularly the urea-containing
      ones, initiated a pronounced pH recovery in dental plaque when chewed after a
      sucrose rinse.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7621492
TI  - Effects of chlorhexidine-fluoride mouthrinses on viability, acidogenic potential,
      and glycolytic profile of established dental plaque.
AB  - Inhibition of dental plaque acidogenicity by chlorhexidine (CHX) mouthrinses has
      been ascribed to a long-lasting bacteriostatic effect due to binding of CHX to
      oral surface structures combined with a slow release rate from the binding sites.
      The present aims were to study the effects of CHX-containing mouthrinses on the
      viability and glycolytic activity of established plaque in order to assess the
      bactericidal versus the bacteriostatic effects. Following 2 days of plaque
      accumulation, three groups of 10 students rinsed with either 12.0 mM NaF, 0.55 mM
      CHX plus NaF, or with 2.2 mM CHX plus NaF. Plaque samples were collected before
      and 90 min after mouthrinsing. The pH in pooled pre- and post-rinse plaque
      samples was recorded before and up to 10 min after the addition of D-[U
      14C]glucose. Total colony-forming units in each sample were determined. High
      performance liquid chromatography analyses showed lactate to be the major
      extracellular glycolytic metabolite in all samples. CHX-NaF markedly reduced the
      colony-forming units, the pH fall from fermentation of glucose, as well as
      glucose consumption and lactate formation, whereas NaF alone exhibited no such
      effects. The reduction of glucose consumption by the CHX-NaF mouthrinses
      corresponded to the reduction of colony-forming units, indicating no
      bacteriostatic effect. The plaque pH in vivo was monitored in each student 90 min
      after mouthrinsing with the test solutions prior to and up to 1 h after a sucrose
      mouthrinse using touch microelectrodes. The CHX-NaF mouthrinses reduced the fall
      in pH significantly (p < 0.05) as compared with the NaF mouthrinse.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7621493
TI  - Effect of an antibacterial varnish on mutans streptococci in plaque from enamel
      adjacent to orthodontic appliances.
AB  - The effect of an antibacterial varnish (Cervitec) on the levels of mutans
      streptococci in plaque adjacent to bonded orthodontic brackets was evaluated in
      18 children using a split-mouth technique with a placebo varnish control. The
      test varnish contained 1% chlorhexidine and 1% thymol as active ingredients. Both
      varnishes were applied on four occasions during a 3-month period, and plaque was
      subsequently collected between 1 week and 6 months after the onset of treatment.
      All teeth involved in the study were carefully examined and clinically assessed
      for enamel demineralization prior to onset of the fixed appliances and
      immediately after debonding. The results showed a more frequent growth of mutans
      streptococci in the dental plaque collected from placebo-treated quadrants as
      compared with the test quadrants on all sampling occasions. The proportion of
      mutans streptococci within the plaque microflora was significantly (p < 0.05
      0.01) lower on the test sides than on the opposite sides at the 1-week and 1
      month examinations. The incidence of incipient enamel lesions around the brackets
      and along the gingival margin was generally low, and no differences were found
      between the test and placebo varnish treated quandrants at the time of debonding.
      The results suggest that mutans streptococci in plaque from orthodontic patients
      can be suppressed effectively by topical applications of an antibacterial
      varnish.

PMID- 7621494
TI  - Effect of dentine and collagen on the lethal photosensitization of Streptococcus
      mutans.
AB  - Suspensions of the cariogenic bacterium, Streptococcus mutans were treated with
      either toluidine blue O or aluminium disulphonated phthalocyanine and then
      exposed to light from a helium-neon or gallium-aluminium-arsenide laser,
      respectively, after passing through demineralized dentine slices. Bacteria were
      also embedded in a collagen matrix prior to sensitization and exposure to the
      laser light. When dentine slices were interposed between the laser light and the
      bacterial suspension, substantial kills (10(7) CFU) were achieved at energy doses
      of 876, 1,752, and 3,504 mJ with the helium-neon laser and of 1,188, 2,376, and
      4,752 mJ with the gallium-aluminium-arsenide laser. There was no apparent
      relationship between the extent of killing and the degree of demineralization of
      the dentine. Prolonging the exposure of the sensitized bacteria to the laser
      light increased the kill achieved. Substantial numbers (10(8) to 10(10) CFU) of
      S. mutans were also killed when embedded in a collagen matrix and exposed to 438
      and 1,314 mJ of helium-neon laser light and 594 and 1,782 mJ of light from the
      gallium-aluminium-arsenide laser. These results imply that lethal
      photosensitization may be effective at killing S. mutans in a carious lesion,
      even when the organism is embedded in demineralized dentine.

PMID- 7621495
TI  - Detection of mutans streptococci in secondary carious lesions using
      immunofluorescent techniques and confocal laser scanning microscopy.
AB  - Secondary caries is one of the major reasons causing restoration failure;
      however, little is known of its microbial etiology, mainly because of the
      difficulties in eliminating bacterial contamination during collection and sample
      preparation. Therefore, the purpose of this study was to investigate the
      feasibility of immunofluorescent techniques and confocal laser scanning
      microscopy for identification and quantification of bacteria in secondary carious
      lesions. Thirty-six extracted human teeth, clinically diagnosed as having
      secondary caries, were used in the study. The teeth were sectioned in half across
      the secondary carious lesion. One half of each tooth was processed using the
      Brown and Hopps histologic staining method for bacterial detection. Sections (100
      microns thick) were obtained from the other half of each tooth for
      immunofluorescence labeling to detect and identify mutans streptococci in the
      subsurface of the lesion using confocal imaging techniques. Mutans streptococci
      were detected in 88.9% of the samples analyzed with the immunofluorescent
      technique. The Brown and Hopps histopathologic examination demonstrated evidence
      of bacteria in 94.4% of the samples. In addition, quantification of bacteria was
      conducted by digitalization of confocal images. The results indicated that the
      immunofluorescence confocal laser scanning microscopy technique was sensitive and
      specific for detection and quantification of mutans streptococci in secondary
      carious lesions.

PMID- 7621496
TI  - Comparisons of in vitro root caries models.
AB  - The purpose of this article is to compare various model systems for the
      production of in vitro root caries and to assess their ability to simulate the
      naturally occurring root caries process. Partially saturated buffer models and
      gel models were evaluated using polarized light microscopy and both qualitative
      and quantitative microradiography. All model systems showed very similar lesion
      formation when examined under polarized light. When microradiographs were
      compared, the systems which contained fluoride, showed clear radiopaque bands
      within the lesion. The bands, which occurred only in the presence of fluoride,
      appeared to be due to remineralization. When using an in vitro system that
      simulates the natural root caries process, it is imperative to understand the
      components of the particular model, as well as its limitations, and to be aware
      of the need for more than one evaluative technique.

PMID- 7621498
TI  - Fluoride distribution of rat molar cementum in relation to age and fluoride
      levels in the drinking water.
AB  - The present study was undertaken to determine the fluoride distribution profile
      in rat molar cementum with age in relation to fluoride in drinking water. Fifty
      four female Wistar rats were used for the experiment. Before the experiment 6
      rats were killed under chloroform anesthesia at 4 weeks of age as controls. The
      remaining 48 rats were divided into two groups: a control group given distilled
      water and the other group given water containing 100 ppm fluoride ad libitum. Six
      rats from each group were killed at the ages of 6, 12, 24, and 48 weeks. The
      fluoride distribution in the molar cementum was analyzed from the surface to the
      cementodentinal junction by abrasive microsampling. The fluoride concentrations
      in molar cementum from control rats on distilled water remained relatively
      constant until 24 weeks. A small increase then occurred between 24 and 48 weeks.
      The fluoride concentration in cementum from rats drinking water containing 100
      ppm fluoride increased markedly with age, both in outer and inner regions of the
      molar cementum for all rats. On the other hand, the fluoride concentration in the
      cementum of older rats drinking water with 100 ppm fluoride was significantly
      higher in the outer than in the inner region of the cementum. It was concluded
      that the fluoride distribution in rat molar cementum may increase throughout life
      in relation to the fluoride level in the drinking water.

PMID- 7621497
TI  - Influence of fluoride applications on some physicochemical surface properties of
      synthetic hydroxyapatite and human dental enamel and its consequences for protein
      adsorption.
AB  - Synthetic hydroxyapatite and human dental enamel (polished and non-polished) were
      subjected to various fluoride applications, i.e., using solutions of sodium
      fluoride (NaF), acidulated phosphate fluoride (APF), and stannous fluoride
      (SnF2). Treatment with APF has a strong influence on the morphology of the
      apatite. All fluorides, in particular SnF2, make the enamel surfaces more
      hydrophobic. NaF and APF applications slightly alter the electrokinetic
      potentials of the surfaces, but SnF2 renders them much more negatively charged.
      The adsorption of the proteins lysozyme and alpha-lactalbumin on these surfaces
      can be explained in terms of electrostatic and hydrophobic interactions between
      the proteins and the sorbent surfaces.

PMID- 7621499
TI  - Formation of phosphate-containing calcium fluoride at the expense of enamel,
      hydroxyapatite and fluorapatite.
AB  - During the caries process complex reactions involving calcium, phosphate,
      hydrogen and fluoride ions as main species take place. In this study the
      precipitation and dissolution reactions occurring in suspensions of enamel,
      hydroxyapatite (HAP) and fluorapatite (FAP) on addition of fluoride were
      investigated under well-defined conditions. pH and pF were monitored; calcium and
      phosphate concentrations were measured at selected times; the solid phases were
      examined by infra-red, X-ray diffraction and transmission electron microscopy.
      Precipitation of phosphate-containing calcium fluoride crystals, CaF2(P), can
      cause severe reduction in the calcium ion concentration and release of hydrogen
      ions from the precipitated phosphate. These reactions result in considerable
      dissolution of enamel, HAP and even of FAP. More of the added mineral dissolves
      with 50 mmol/l fluoride than with 10 mmol/l fluoride, mainly due to the greater
      reduction in calcium ion concentration. This work shows that phosphate-containing
      calcium fluoride is most likely an important compound to be considered in the
      caries process.

PMID- 7621500
TI  - The influence of air-drying on hyper-remineralization of demineralized dentine: a
      study on bulk as well as on thin wet section of bovine dentine.
AB  - The influence of air-drying on the remineralization of demineralized bovine
      dentine was examined in wet bulk samples, in dried bulk samples as well as in wet
      thin sections. Bulk samples of bovine dentine were first demineralized in an
      acidic gel (pH = 5) at 37 degrees C for 3 weeks. After 24-hour pre-treatment of
      either air-drying or immersion in water, the bulk samples were remineralized in a
      solution containing 1.5 mM Ca, 0.9 mM phosphate and 10 ppm F (pH = 7) at 37
      degrees C for 2, 4 or 8 days. Separately thin sections prepared from
      demineralized bulk dentine were immersed in water for 24 h and were also exposed
      to the remineralization solution for 2, 4 or 8 days. The results show that air
      drying of the bulk samples increased remineralization of dentine considerably;
      the microradiographic parameters (ld, delta Z and la) show that the degree of
      remineralization ranks: thin wet sections > bulk dried > bulk wet. Especially,
      the remineralization inside lesions was greatly enhanced in thin sections and
      dried samples. It is presumed that the increased remineralization in dried
      samples is caused by a 'sponge effect', in which the remineralization fluid is
      sucked up in a dried shrunken lesion, resulting in fast and deep penetration of
      remineralization solution and/or presumably increased nucleation.

PMID- 7621501
TI  - Investigation of the effects of aluminum mouthrinses on rat dental caries and
      plaque.
AB  - The effects of topically applied mouthrinses containing AlCl3, or AlK(SO4)2 on
      dental caries and plaque were investigated in a rat model. For comparison, NaF
      and a two-step treatment of AlCl3 and NaF were also tested. Six groups of 20
      weanling rats were inoculated with Streptococcus sobrinus 6715 and provided a
      caries-inducing diet and distilled water ad libitum. Test agents were topically
      applied twice daily 5 days per week at a concentration of 0.037 mol/l in a
      mouthrinse vehicle and were compared with a vehicle control rinse and a distilled
      water control. After 10 weeks none of the treatments reduced plaque amounts
      relative to the controls. The AlCl3 and AlK(SO4)2 rinses significantly reduced
      both smooth-surface and sulcal caries by approximately 40%. The cariostatic
      activity of the aluminum rinses was equivalent to an equimolar NaF mouthrinse on
      smooth surface lesions, but was statistically less than NaF on sulcal caries. The
      two-step treatment with AlCl3 and NaF indicated numerically additive effects, but
      the results were not statistically better than with NaF alone. Dentine caries
      progression paralleled the enamel caries prevalence results. No deaths,
      toxicologic effects, or inhibition of growth rates were observed in any treatment
      group. This study confirmed that topically applied solutions of aluminum salts
      inhibited caries formation in the rat caries model and showed that the
      cariostatic activity of aluminum was maintained in a compatible mouthrinse
      vehicle.

PMID- 7621503
TI  - Depletion of catalytic and regulatory subunits of protein kinase CK2 by antisense
      oligonucleotide treatment of neuroblastoma cells.
AB  - 1. The use of antisense oligonucleotides to inhibit expression of the genes
      coding for the catalytic (alpha/alpha') and regulatory (beta) subunits of protein
      kinase casein kinase 2 (CK2) has allowed study of the role of this enzyme in
      mouse neuroblastoma cells. 2. Selective depletion of catalytic (alpha/alpha')
      subunits results in the blocking of neuritogenesis. The depletion of catalytic
      subunits also affects the sorting of the regulatory (beta) subunit of CK2, as the
      absence of catalytic subunits prevents the translocation of the regulatory
      subunit to the nuclei. These results emphasize the existence of a control
      mechanism linking the expression and sorting of CK2 catalytic and regulatory
      subunits. 3. Selective depletion of the regulatory (beta) subunit of protein
      kinase CK2 by an specific antisense oligonucleotide causes partial inhibition of
      neurite extension.

PMID- 7621502
TI  - c-fos antisense reduces expression of Krox 24 in rat caudate and neocortex.
AB  - 1. The aim of this study was to investigate the neurochemical effects and measure
      the anatomical spread of infusion of c-fos antisense (AS) DNA into the striatum.
      2. Rats were anesthetized and infused in opposing striata with c-fos AS and c-fos
      sense (S) DNA. Ten hours later they were injected with apomorphine (2 mg/kg,
      i.p.) and 20 min later they were overdosed with sodium pentobarbital and their
      brains either perfused or frozen. Vibratome-cut sections were immunostained for
      the detection of c-fos, JunB, Krox 24, somatostatin, substance P, dynorphin,
      tyrosine hydroxylase, and enkephalin. Cryostat-cut sections from the caudate were
      immunostained for the detection of c-fos, JunB, and Krox 24, as well as in situ
      hybridization for proenkephalin mRNA. Sections from the globus pallidus were used
      for the autoradiographic localization of D2 dopamine and A2a adenosine receptors.
      Sections from the substantia nigra were used for the autoradiographic
      localization of D1 dopamine and cannabinoid receptors. A second group of rats
      were injected in opposing striata with biotin-labeled c-fos AS DNA and c-fos S
      DNA. Ten hours later they were challenged with apomorphine (2 mg/kg, i.p.) and 20
      min later brains were either perfused or frozen. Sections from these brains were
      cut throughout the rostral-caudal extent of the forebrain and the biotin labeled
      AS DNA was localized. 3. Krox 24 was expressed at high levels on the sense side
      of the brain in the striatum and overlying neocortex. However, on the AS-injected
      side there was a reduction in Krox 24 expression in striatum and overlying
      cortex. The biotin-labeled AS studies confirmed that the striatal infusion spread
      throughout the dorsal striatum as well as the overlying neocortex. We did not
      detect any changes in neurotransmitter receptors, neuropeptides, or tyrosine
      hydroxylase in AS/S-injected rat brains. 4. These results demonstrate that c-fos
      AS reduces Krox 24 expression in striatal and neocortical neurons but does not
      change the expression of a number of other proteins involved in basal ganglia
      function. Whether this effect is due to nonspecific actions of c-fos AS or to its
      effects on a component of the transduction pathway responsible for basal Krox 24
      expression (NMDA receptors?) is unknown.

PMID- 7621504
TI  - c-fos expression in the amygdala: in vivo antisense modulation and role in
      anxiety.
AB  - 1. The amygdaloid complex is a key structure in mechanisms of fear and anxiety.
      Expression of the immediate-early gene c-fos has been reported in the central
      nucleus of the amygdala following various stressors, but the functional role of
      this phenomenon has remained unknown. 2. c-fos expression was observed in the
      central nucleus when rats were subjected to a pharmacologically validated animal
      model of anxiety, the Vogel conflict test, but not after mere exposure to the
      test apparatus. Bilateral amygdala injection of a 15-mer phosphorothioate c-fos
      antisense oligodeoxynucleotide prior to testing blocked conflict-induced c-fos
      expression and had behavioral effects similar to those of established antianxiety
      drugs. 3. Separate experiments determined that antisense treatment did not affect
      conflict behavior by acting on shock thresholds or drinking motivation. 4. These
      findings provide evidence that neuronal activation and c-fos induction in the
      amygdala may be of importance for mechanisms of fear and anxiety.

PMID- 7621505
TI  - Modulation of the PC12 cell response to nerve growth factor by antisense
      oligonucleotide to amyloid precursor protein.
AB  - 1. The amyloid precursor protein (APP) is widely distributed among eukaryotic
      cells, however, its precise role in cellular functioning is not fully clarified.
      APP is glycoprotein membrane constituent and it may facilitate membrane
      associated functions. 2. The aim of the present study was to examine the
      possibility that APP may play a role in mediating cellular trophic responses. The
      methods made use of an antisense oligonucleotide that was prepared to the 5'
      terminus of APP and shown specifically to reduce the level of APP isoforms. 3. In
      sequential mixing experiments it was observed that the APP antisense
      oligonucleotide did not significantly modify the trophic response of PC12 cells
      pretreated with nerve growth factor (NGF). However, pretreatment of cells with
      the antisense oligonucleotide diminished NGF-induced increases in cellular size
      and neurite length. 4. These observations suggest that APP may play a role in
      modulating the trophic response. The combined use of APP antisense
      oligonucleotides and neurotrophic agents may find clinical utility in the
      treatment of Alzheimer-type dementia since it is known that NGF normally causes
      increases in APP levels.

PMID- 7621506
TI  - Antisense inhibition of low-affinity nerve growth factor receptor in kidney
      cultures: power and pitfalls.
AB  - 1. Antisense inhibition of gene expression implies that the expression of the
      target protein is selectively inhibited at either the translational or the
      transcriptional level by complementary DNA or RNA constructs that are
      antiparallel to the target sequence. The antisense inhibition strategy provides
      means to study the roles of individual proteins and has, in spite of its
      limitations, gained a wide range of both therapeutic and experimental
      applications. 2. In developmental biology, protein expression has been
      selectively inhibited by the use of antisense gene transfection and by antisense
      deoxyoligonucleotides. The transfectability of embryonic tissues is variable, but
      in general fetal and embryonic cells take up foreign DNA relatively efficiently,
      in particular, short deoxyoligonucleotides that penetrate mesenchymal cells
      within a few hours without any manipulation. 3. We have now evaluated the
      advantages and pitfalls of antisense inhibition by deoxyoligonucleotides in organ
      culture and describe our experience from the inhibition of low-affinity nerve
      growth factor receptor expression in embryonic mouse and rat kidneys. 4. The
      expression of nerve growth factor receptor can be specifically inhibited by
      deoxyoligonucleotides, but the target sequence-dependent window of, in
      particular, phosphorothioate-modified oligonucleotides is quite narrow. The
      culture conditions affect the response to the oligonucleotides and their cellular
      incorporation is variable with respect to the cell type and stage of
      differentiation.

PMID- 7621507
TI  - Antisense inhibition of butyrylcholinesterase gene expression predicts adverse
      hematopoietic consequences to cholinesterase inhibitors.
AB  - 1. To investigate the possibility that cholinesterase inhibitors may cause
      adverse hematopoietic effects, we employed antisense oligodeoxynucleotides
      selectively inhibiting butyrylcholinesterase gene expression (AS-BCHE).
      Complementary sense (S) oligonucleotides served as controls. 2. In primary bone
      marrow cell cultures grown with interleukin 3 (IL-3), AS-BCHE but not S-BCHE
      reduced growth of megakaryocyte colony-forming units (CFU-MK) in a dose-dependent
      manner at the micromolar range. 3. In cultures grown with IL-3, transferrin, and
      erythropoietin (Epo), cell counts increased up to twofold, yet colony counts (CFU
      GEMM) remained unchanged under AS-BCHE treatment. 4. Electrophoretic measurements
      of DNA ladder as an apoptotic index revealed that the above oligonucleotide
      effects were not due to nonspecific induction of programmed cell death. 5.
      Differential cell counts demonstrated increased myeloidogenesis and reduced
      levels of early megakaryocytes in CFU-GEMM under AS-BCHE, suggesting requirement
      of the BuChE protein for megakaryopoiesis. 6. In vivo injection of AS-BCHE
      reduced BCHE mRNA levels in both young and mature megakaryocytes for as long as
      20 days, as shown by in situ hybridization. 7. Ex vivo growth of primary bone
      marrow cells revealed a twofold reduction in CFU-MK colonies grown from the AS
      BCHE- but not the S-BCHE-injected mice, 15 days posttreatment. 8. These findings
      demonstrate that deficient butyrylcholinesterase expression, and hence
      interference with this enzyme's activity through treatment with or exposure to
      cholinesterase inhibitors, may cause hematopoietic differences in treated
      patients.

PMID- 7621508
TI  - Cellular uptake of intracerebroventricularly administered biotin- or digoxigenin
      labeled antisense oligodeoxynucleotides in the rat.
AB  - 1. Antisense oligodeoxynucleotides (ODNs) internally labeled with biotin or
      digoxigenin were injected into the lateral ventricle of rats and the distribution
      of the labeled ODNs was examined at several timepoints following the
      intracerebroventricular (icv) injections. The stability of these injected
      antisense ODNs, which had no backbone modifications, was also studied by
      performing recovery experiments. 2. The most intense labeling was observed near
      the injection site, in periventricular areas, and in perivascular regions. Many
      of the labeled cells appeared to be neurons, and both the cytoplasm and the
      nuclei were stained. The labeled cells were detected 15 min after icv injection,
      demonstrating that the antisense ODNs were taken up rapidly by cells in the
      parenchyma. The digoxigeninated antisense ODNs were presented in both the
      cytoplasmic and the nuclear fractions of rat brain extracts, however, the levels
      appeared to be much lower in the nuclear fractions. 3. Antisense ODNs injected
      into the lateral ventricle seemed to follow the bulk flow of cerebrospinal fluid
      (CSF), i.e., from the injection site in the lateral ventricle, through the
      ventricular system, to the subarachnoid spaces and the perivascular spaces. From
      the ventricular and perivascular spaces, the antisense ODNs diffused into the
      extracellular space and were taken up by cells. The full-length digoxigeninated
      antisense ODNs were detectable within cells after only 15 min, indicating their
      rapid uptake. In addition, the antisense ODNs appeared to be relatively stable in
      the brain since the full-length digoxigeninated ODNs were still detectable after
      4 hr.

PMID- 7621509
TI  - The role of Jun transcription factor expression and phosphorylation in neuronal
      differentiation, neuronal cell death, and plastic adaptations in vivo.
AB  - 1. To investigate the role of the Jun transcription factors in neuronal
      differentiation, programmed neuronal cell death, and neuronal plasticity, we used
      phosphorothioate oligodeoxynucleotides (S-ODN) to inhibit selectively the
      expression of c-Jun, JunB, and JunD. 2. We have shown previously that in contrast
      to c-Jun, the JunB and JunD transcription factors are negative regulators of cell
      growth in various cell lines. Here we confirm this finding in primary human
      fibroblasts. 3. c-Jun and JunB are counterplayers not only with respect to
      proliferation, but also in cell differentiation. Since JunB expression is
      essential for neuronal differentiation, we analyzed possible posttranslational
      modifications of JunB after induction of PC-12 cell differentiation by nerve
      growth factor (NGF). 4. JunB was strongly phosphorylated after induction of PC-12
      cell differentiation with NGF but not after stimulation of cell proliferation
      with serum. Thus, while cell proliferation is associated with c-Jun
      phosphorylation, cell differentiation is correlated with JunB phosphorylation.
      This supports the finding that c-Jun and JunB play antagonistic roles in both
      proliferation and differentiation. 5. The JunB transcription factor together with
      the c-Fos transcription factor is also induced in vivo in the suprachiasmatic
      nucleus (SCN) of rat brain after a light stimulus that induces resetting of the
      circadian clock. 6. Using antisense oligonucleotides injected into the third
      ventricle, we selectively cosuppressed the two transcription factors in vivo as
      shown by immunohistochemistry. Expression of c-Jun, JunD, and FosB was not
      affected. Inhibition of JunB and c-Fos expression prevented the light-induced
      phase shift of the circadian rhythm. In contrast, rats injected with a randomized
      control oligonucleotide showed the same phase shift as untreated animals. 7. In
      primary rat hippocampal cultures, anti-c-jun S-ODN selectively inhibited neuronal
      cell death and promoted neuronal survival. This indicates a causal role of c-Jun
      in programmed neuronal cell death. 8. These findings demonstrate the essential
      role of inducible transcription factors in the reprogramming of cells to a
      different functional state. Jun transcription factors play an essential role not
      only in fundamental processes such as cell proliferation, differentiation, and
      programmed neuronal cell death, but also in such complex processes as plastic
      adaptations in the mature brain. The inhibition of neuronal cell death by anti-c
      jun S-ODN shows the great therapeutic potential of selective antisense
      oligonucleotides.

PMID- 7621510
TI  - The application of antisense oligonucleotide technology to the brain: some
      pitfalls.
AB  - 1. Amphetamine-induced c-fos and egr-1 expression in the striatum was used as a
      model in which to study the effects of antisense oligodeoxynucleotides (ODNs)
      directed at c-fos. Using direct infusions of ODNs into the striata of animals we
      have demonstrated that c-fos antisense ODNs retain most of their biological
      activity with 2- or 3-base substitutions. The c-fos antisense and mismatch ODNs
      attenuated Fos immunoreactivity but had little effect on Egr-1 immunoreactivity.
      2. In another group of studies examining the role of c-fos in amygdala kindling,
      we have demonstrated that ODNs cause neurotoxic damage following repeated daily
      infusions into the amygdala. The damage observed was greatly diminished when the
      time interval between infusions was extended.

PMID- 7621511
TI  - Inhibition of gene expression with ribozymes.
AB  - 1. Ribozymes can be designed to cleave in trans, i.e. several substrate molecules
      can be turned over by one molecule of the catalytic RNA. Only small molecular
      weight ribozymes, or small ribozymes, are discussed in this review with
      particular emphasis on the hammerhead ribozyme as this has been most widely used
      for the inhibition of gene expression by cleavage of mRNAs. 2. Cellular delivery
      of the ribozyme is of crucial importance for the success of inhibition of gene
      expression by this methodology. Two modes of delivery can be envisaged,
      endogenous and exogenous delivery. Of the former several variants exist,
      depending on the vector used. The latter is still in its infancy, even though
      chemical modification has rendered such ribozymes resistant against degradation
      by serum nucleases without impairment of catalytic efficiency. 3. Various
      successful applications of ribozymes for the inhibition of gene expression are
      discussed, with particular emphasis on HIV1 and cancer targets. These examples
      demonstrate the promise of this methodology.

PMID- 7621512
TI  - Study of stimulus-secretion coupling in single cells using antisense
      oligodeoxynucleotides and patch-clamp techniques to inhibit specific protein
      expression.

PMID- 7621513
TI  - Design and application of antisense oligonucleotides in cell culture, in vivo,
      and as therapeutic agents.
AB  - 1. Synthetic oligonucleotides can inhibit the expression of a gene in a sequence
      specific manner on the transcriptional and translational level. These molecules
      are usually referred to as antisense oligonucleotides. 2. Antisense mediated
      inhibition of gene expression is a valuable tool to analyze the function of a
      gene in vivo and can also be used for therapeutic gene suppression. 3. A number
      of factors such as the mode of action, specificity, chemistry, and pharmacology
      must be carefully considered for the design and successful application of
      antisense oligonucleotides. 4. Assay systems and controls must be chosen as to
      assure that the observed biological effects of antisense oligonucleotides do in
      fact reflect the result of a specific gene inhibition. 5. This article critically
      discusses these factors in view of the literature and our own experience with a
      wide range of cell types and animal models, targeting different genes. The
      emphasis is on the use of phosphorothioate oligodeoxynucleotides in cell
      cultures, in vivo, and as potential drugs.

PMID- 7621514
TI  - Antisense strategy unravels tau proteins as molecular risk factors for glutamate
      induced neurodegeneration.
AB  - 1. We investigated the possible involvement of tau proteins in the neurotoxic
      process activated by glutamate using the oligonucleotide antisense strategy. 2.
      We found that pretreatment of granule cells with an antisense oligonucleotide of
      the tau gene completely prevented the increase in tau immunoreactivity induced by
      glutamate. 3. A significant amount of the tau antisense oligonucleotide (about 1
      to 2% of total) was taken up by the cells and remained stable in the cells for at
      least 60 min. A dose-response study revealed that 25 microM tau antisense
      oligonucleotide was the most efficacious concentration in terms of prevention of
      glutamate-induced tau immunoreactivity increases, without affecting basal tau
      expression. Higher concentrations of tau oligonucleotide antisense reduced tau
      immunoreactivity in control cells. 4. Significantly, the concentration-response
      curve of glutamate for inducing neuronal death in cells pretreated with tau
      antisense oligonucleotide showed a shift to the right compared to those obtained
      in untreated or tau sense oligonucleotide-treated cells. 5. Since inhibition of
      tau synthesis does not completely prevent but only decreases the neuronal
      sensitivity to glutamate, it is tempting to speculate that accumulation of tau
      within the neuron in response to glutamate represents one of the molecular risk
      factors lowering the safety margin of neurons to excitotoxic-induced injury.

PMID- 7621515
TI  - Corticotropin-releasing hormone (CRH) antisense oligodeoxynucleotide treatment
      attenuates social defeat-induced anxiety in rats.
AB  - 1. The neuropeptide corticotropin-releasing hormone (CRH) is the main mediator of
      the neuroendocrine and behavioral response to stress. End-capped phosphorothioate
      antisense and sense oligodeoxynucleotides (ODN) corresponding to the start coding
      region of rat CRH mRNA were infused intracerebroventricularly (30 micrograms/3
      microliters per injection) three times at 12 hr intervals. Six hours after the
      last injection rats were subjected to social defeat stress and subsequently
      tested on the elevated plus maze. 2. Socially defeated CRH antisense-treated rats
      displayed markedly reduced anxiety-related behavior, as they spent significantly
      more time in the open arms of the plus maze compared to sense ODN- and vehicle
      treated animals. 3. In controls, social defeat evoked a stress-induced elevation
      of CRH mRNA and CRH in the hypothalamus and a significant increase in plasma
      corticotropin (ACTH) levels. These parameters were attenuated in antisense
      injected rats. 4. Our results suggest that CRH antisense treatment is effectively
      suppressing the neuroendocrine and behavioral effects of social defeat.

PMID- 7621517
TI  - Expression of fibronectin, laminin and ribosomes in normal and nocodazole-treated
      neonatal heart cells in culture: a study by laser scanning confocal microscopy
      and immunocytochemistry.
AB  - Polyclonal and monoclonal antibodies were used to examine the effects of the
      synthetic microtubule disruptive drug nocodazole on the subcellular expression of
      fibronectin, laminin, and ribosomes in primary cultures of neonatal cardiac
      ventricular cells. Non-invasive serial optical sectioning was carried out by
      immunolaser scanning confocal microscopy. In addition, fibronectin and laminin
      were immunolabelled with peroxidase or gold conjugates for electron-microscopic
      examination. Immunolabelling for the large 60S ribosome subunit in fibroblast
      like non-myocytes showed that punctate ribosome structures with a multi-subunit
      composition were present in perinuclear region. Double immunostaining with
      antibodies directed against ribosomes and cellular fibronectin indicated that the
      punctate structures were cisternae of the rough endoplasmic reticulum. No clear
      effects of nocodazole treatment were detected on the distribution of cytoskeleton
      bound ribosomes. Following immunolabelling for both glycoproteins and double
      immunolabelling for cellular fibronectin and the 60S ribosome subunit,
      fibronectin and laminin were found in the perinuclear cisternae of the rough
      endoplasmic reticulum and in pleomorphic secretory vesicles. The cisternal stacks
      of the Golgi complex appeared either unstained or were only weakly labelled. When
      these cells were exposed to nocodazole, fibronectin and laminin accumulated in
      peripheral parts of the cytoplasm, including cellular processes. These peripheral
      accumulation of immunostaining for fibronectin and laminin did not reflect Golgi
      staining, as shown by double labelling experiments versus wheat-germ-agglutinin
      staining, and, by exposing cultures to a high dose of brefeldin A.

PMID- 7621516
TI  - Oxytocin-producing and vasopressin-producing eosinophils in the mouse spleen:
      immunohistochemical, immuno-electron-microscopic and in situ hybridization
      studies.
AB  - Oxytocin-like and vasopressin-like immunoreactive cells, and the cells expressing
      mRNAs for these peptides in the spleen of the C57BL/6 mouse were studied by
      immunohistochemistry, immuno-electron microscopy and in situ hybridization.
      Immunoreactive cells were distributed mainly in the splenic cord and marginal
      zone, whereas there were few in the lymphocyte-packed periarteriolar-lymphoid
      sheath, lymphoid follicle and germinal center. More numerous vasopressin-positive
      cells were seen in the splenic cord. The colocalization of oxytocin-like and
      vasopressin-like immunoreactivity in the same cells was identified by the
      investigation of mirror sections. By the pre-embedding immuno-electron
      microscopic method using antisera against oxytocin and vasopressin,
      immunopositive reaction products were localized in the matrix around the specific
      granules, small clear vesicles and mitochondrial membrane of the eosinophils. No
      immunoreactivity to these peptides was found within the specific granules of the
      eosinophils. In situ hybridization with synthetic oligonucleotide probes labeled
      with 32P revealed the presence of mRNAs for oxytocin and vasopressin in the cells
      of the spleen, the distribution of the mRNAs for these peptides being the same as
      that of immunopositive cells. These observations suggest that eosinophils
      synthesize both oxytocin and vasopressin and store them in the matrix. Possible
      differences in the mechanism of synthesis and storage of these peptides between
      peripheral eosinophils and hypothalamic neurons are discussed.

PMID- 7621518
TI  - Immunohistochemical characteristics of chicken spleen ellipsoids using newly
      established monoclonal antibodies.
AB  - Ellipsoids, the extra-vasculature sites surrounding penicilliary capillaries of
      the chicken spleen, play critical roles in the immune response and also in the
      clearance of pathogens or other particles. The meshwork of ellipsoids is formed
      by fibroblastic reticular cells. To characterize ellipsoidal reticular cells, a
      series of monoclonal antibodies against the chicken spleen have been developed.
      Of these antibodies, CSA-1 antibody reacts with fibroblastic reticular cells in
      ellipsoids and with endothelial cells. The reticular nature of positive cells in
      ellipsoids is indicated by immuno-electron microscopy, and by double staining
      with anti-heat-shock protein 47 kDa (hsp47) antibody. The reaction of CSA-1 with
      reticular cells is limited in ellipsoids; CSA-1 does not react with reticular
      cells in other lymphoid organs. These findings indicate that ellipsoidal
      reticular cells share the antigen with endothelial cells. Ontogenic studies
      reveal that, on embryonic day 18, the development of ellipsoids is completed,
      penicilliary capillaries become fenestrated, and CSA-1 expression in ellipsoids
      begins. These findings suggest that CSA-1 is expressed on the cell surface of
      ellipsoidal reticular cells once they are exposed to blood flow.

PMID- 7621520
TI  - Cerebrospinal fluid-contacting neurons in the paraventricular organ and in the
      spinal cord of the quail embryo: a fluorescence-histochemical study.
AB  - Although the cerebrospinal fluid-contacting neurons of the avian paraventricular
      organ exhibit considerable amounts of catecholamines, they show no tyrosine
      hydroxylase immunoreactivity. In the quail embryo, the development of these
      neurons has been studied using the paraformaldeyde-glutaraldeyde method for the
      fluorescence-histochemical localization of catecholamines. The timing of the
      appearance of catecholamine fluorescence in cerebrospinal fluid-contacting
      neurons and that in catecholamine-containing neurons of the brainstem have been
      compared. The first neurons displaying catecholamine fluorescence are found
      within the locus coeruleus and the nucleus subcoeruleus ventralis on the 5.5th
      day of incubation. Catecholaminergic neuronal groups of the medulla and
      mesencephalon can be identified by embryonic day 7, and fluorescent cerebrospinal
      fluid-contacting neurons of the hypothalamic paraventricular organ can be first
      recognized at the 8th day of incubation. If the catecholamine content of
      cerebrospinal fluid-contacting neurons that lack tyrosine hydroxylase depends
      upon an uptake mechanism, it may be significant that, in fluorescence
      histochemical preparations, these neurons can be identified 1-3 days later than
      those in which catecholamines are synthesized and from which catecholamines are
      released at an earlier developmental stage. Moreover, cerebrospinal fluid
      contacting neurons that have previously been shown to be tyrosine-hydroxylase
      immunoreactive, and that lie at the spinal-medullary junction display a different
      developmental pattern. By fluorescence histochemistry, they can be detected only
      by embryonic day 10.5. The chemical, developmental and topographical differences
      suggest that the catecholamine-containing cerebrospinal fluid-contacting elements
      of the paraventricular organ and those of the spinal cord represent two different
      subsets of cerebrospinal fluid-contacting neurons whose respective functional
      roles remain to be investigated.

PMID- 7621521
TI  - Histology and lectin-binding patterns in the skin of the terrestrial horned frog
      Ceratophrys ornata.
AB  - The terrestrial horned frog, Ceratophrys ornata, lives on a wet substratum and
      absorbs water through the ventral epidermis; water is lost by evaporation from
      the dorsal skin. Thus, this species may be useful as a model for determining
      whether or not skin histology and lectin-binding patterns, indicative of
      glycoconjugates, are related to skin functions such as osmoregulation and water
      balance. With this in mind, a histological and lectin-histochemical study was
      carried out on dorsal and ventral skin of aquatic tadpoles and of a young
      terrestrial frog of C. ornata. Sections of skin were stained with various dyes to
      demonstrate general histological features and with two horseradish peroxidase
      (HRP)-conjugated lectins, Ulex europaeus agglutinin (UEA 1) and soybean
      agglutinin (SBA) which bind to specific terminal sugar residues of
      glycoconjugates, namely L-fucose and N-acetyl-D-galactosamine or D-galactose,
      respectively. In early stage tadpoles both lectin-binding patterns were similar
      in the bilaminar epidermis of dorsal and ventral skin (i.e., each lectin stained
      the apical cell layer). However, metamorphic changes resulted in a young frog
      with typical adult-type skin composed of a stratified squamous epidermis and
      three distinct types of glands containing glycoconjugates in their secretions.
      Strikingly different lectin-binding patterns were evident in the epidermis from
      dorsal and ventral regions of the body. The epidermis from the dorsal region was
      stained by both lectins; in contrast, that from the ventral region, although
      stained strongly by HRP-SBA, did not react with HRP-UEA 1, indicating that few,
      if any, fucose residues were present in the ventral epidermis.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7621519
TI  - Pro-enkephalin opioid peptides are abundant in porcine and bovine splenic nerves,
      but absent from nerves of rat, mouse, hamster, and guinea-pig spleen.
AB  - The opioidergic innervation of the mammalian spleen and possible species
      differences were investigated. Light-microscopic immunohistochemistry revealed
      that splenic nerves of bovine and porcine spleen, but not of rat, mouse, hamster
      and guinea-pig spleen contained proenkephalin-derived opioidergic innervation.
      Immunoreactivity to both prodynorphin and pro-opiomelanocortin was absent from
      splenic nerves. In bovine and porcine spleen, fibers immunoreactive for met
      enkephalin, met-enkephalin-Arg-Phe, met-enkephalin-Arg-Gly-Leu, leu-enkephalin
      and peptide F formed perivascular plexus, traveled in trabecular connective
      tissue, and extended into the capsule. Spatial relationships with immune cells
      were apparent in the white and red pulp, excluding lymphoid follicles.
      Colocalization of enkephalin immunoreactivity with immunoreactivities for tyrosin
      hydroxylase, dopamin-beta-hydroxylase, and neuropeptide Y, but not for substance
      P or calcitonin gene-related peptide were found. Our results provide evidence
      that opioid expression in splenic innervation is strongly species-dependent and
      exclusively proenkephalin-derived. Colocalization with marker enzymes of
      noradrenergic neurons indicates a mainly postganglionic sympathetic origin of
      proenkephalinergic splenic innervation. Opioidergic perivascular nerves probably
      control the splenic blood flow. A close interrelationship of opioidergic fibers
      with immune cells provides the anatomical basis for direct effects of neurally
      released opioids on splenic immune functions.

PMID- 7621522
TI  - Immunocytochemical, electrophoresis, and immunoblot analysis of Heliothis
      virescens gap junctions isolated in the presence and absence of protease
      inhibitors.
AB  - Gap junction-enriched fractions were prepared from larvae of the tobacco budworm
      Heliothis virescens using the NaOH procedure in the presence or absence of
      protease inhibitors and were analyzed by SDS-PAGE immunoblotting and EM
      immunocytochemistry. Protease inhibitor fractions contained a 48-kDa protein in
      addition to the approximately 10 proteins in fractions with and without
      inhibitors. Three polyclonal antibodies were used as probes for gap junction
      plaques and proteins: R16, against an approximately 40-kDa candidate gap junction
      protein from Drosophila melanogaster; R17, against the 40-kDa candidate gap
      junction protein from H. virescens; and R18AP, an affinity purified antibody
      against a consensus sequence of N-terminal amino acids 2-21 of the H. virescens
      40-kDa protein. R16, R17, and R18AP stain the 40- and 48-kDa proteins, R16 and
      R18AP stain a 64-kDa protein, and R16 stains an approximately 30-kDa protein in
      the absence of inhibitors. Inclusion of protease inhibitors had no effect on gap
      junction ultrastructure. R16 and R17 label gap junction plaques in crude membrane
      and NaOH fractions, whereas R18AP exhibits only a low level of reactivity with
      gap junctions in crude membrane fractions and none with gap junctions in NaOH
      fractions. The results show that the 30-, 40-, 48- and 64-kDa proteins are
      immunologically related and are associated with gap junctions in H. virescens,
      the N-terminus of the 40-kDa protein is relatively inaccessible or easily lost,
      and the 48-kDa protein is protease-sensitive.

PMID- 7621523
TI  - Composition in situ and in vitro of vascular smooth muscle laminin in the rat.
AB  - Vascular smooth muscle cells are surrounded by a basal lamina containing an array
      of macromolecules: included among these are the laminins, a family of oligomeric
      glycoproteins composed of subunits encoded by different genes. In this study, we
      have used monoclonal antibodies to several of these subunits, including S
      laminin, laminin B2, and laminin B1, to study these proteins in tail artery,
      superior mesenteric artery, and aorta of rats. In situ, immunostaining for the B2
      and S chains was present in the basal lamina, between the smooth muscle cells,
      throughout the tunica media. In contrast, B1 chain immunostaining was
      concentrated around cells in the inner media. To investigate whether smooth
      muscle cells can produce S-laminin, laminin B2, and laminin B1, smooth muscle
      cells from the superior mesenteric artery were grown in culture and laminin
      subunit expression determined. In early culture (4 days), immunostaining showed
      abundant laminin B2 and less B1 synthesis and incorporation into the matrix.
      Staining for S-laminin was even less intense than for B1 and was localized to
      areas where cells were densely packed. The same pattern of S-laminin
      immunostaining was seen during early culture in cells grown on fibronectin, type
      IV collagen, or gelatin. Immunoblotting detected S-laminin in the conditioned
      medium from early cultured cells. In later culture (12 days), S-laminin
      incorporation into the matrix increased markedly compared to incorporation at 4
      days. At this time, cells are much more densely packed and multilayered with
      extensive matrix accumulation. Cyclical stretching of cells in vitro did not
      increase immunostaining for S-laminin. Together these data show that S-laminin is
      a component of the arterial media in situ and that in vitro S-laminin is
      synthesized by smooth muscle cells. Increased incorporation of S-laminin into the
      matrix in later culture correlates with the presence of a more extensive matrix,
      suggesting that matrix organization may be critical to S-laminin incorporation.

PMID- 7621524
TI  - Reduced laminin immunoreactivity in the blood vessel wall of ageing rats
      correlates with reduced innervation in vivo and following transplantation.
AB  - Changes in extracellular matrix composition and/or organization, and in
      particular in the ratio of axonal growth-promoting components such as laminin to
      growth-inhibiting molecules, could contribute to the degenerative changes
      observed in the innervation of some peripheral tissues in old age. We have
      investigated this issue by evaluating laminin content or accessibility at various
      locations on blood vessels where we had previously studied age-related
      alterations in innervation density. We have employed a morphological approach,
      measuring laminin immunoreactivity by a densitometric application of confocal
      microscopy, because more conventional biochemical techniques would have been
      unable to distinguish specific, localized changes in laminin at sites accessible
      to nerves from heterogeneous changes in other areas of the vessel wall, such as
      the endothelial basal lamina. We found that in 24-month-old rats laminin
      immunoreactivity is decreased by 50% at the medial-adventitial border in
      association with the outer layer of smooth muscle cells, where a parallel
      decrease is observed in innervation density. Axonal terminals were shown to have
      access to laminin in this region of the blood vessel wall by double staining with
      laminin and a general neuronal marker. Changes in laminin immunoreactivity were
      region-specific on the same blood vessel, thus excluding the possibility of a
      generalized decrease in immunoreactivity in old age. For example, in the basilar
      artery intensity of laminin immunoreactivity decreased in old age at the medial
      adventitial border, but showed no change in endothelial cell basal lamina and in
      the adventitia. Moreover, we performed in oculo transplants of blood vessels
      displaying differences in laminin immunoreactivity and found that the density of
      innervation correlated with the intensity of laminin staining, thus lending
      further support to the hypothesis that laminin might play a role in nerve fibre
      atrophy in old age.

PMID- 7621526
TI  - Putative neurohemal areas in the peripheral nervous system of an insect, Gryllus
      bimaculatus, revealed by immunocytochemistry.
AB  - The morphology and position of putative neurohemal areas in the peripheral
      nervous system (ventral nerve cord and retrocerebral complex) of the cricket
      Gryllus bimaculatus are described. By using antisera to the amines dopamine,
      histamine, octopamine, and serotonin, and the neuropeptides crustacean
      cardioactive peptide, FMRFamide, leucokinin 1, and proctolin, an extensive system
      of varicose fibers has been detected throughout the nerves of all neuromeres,
      except for nerve 2 of the prothoracic ganglion. Immunoreactive varicose fibers
      occur mainly in a superficial position at the neurilemma, indicating
      neurosecretory storage and release of neuroactive compounds. The varicose fibers
      are projections from central or peripheral neurons that may extend over more than
      one segment. The peripheral fiber varicosities show segment-specific arrangements
      for each of the substances investigated. Immunoreactivity to histamine and
      octopamine is mainly found in the nerves of abdominal segments, whereas serotonin
      immunoreactivity is concentrated in subesophageal and terminal ganglion nerves.
      Immunoreactivity to FMRFamide and crustacean cardioactive peptide is widespread
      throughout all segments. Structures immunoreactive to leucokinin 1 are present in
      abdominal nerves, and proctolin immunostaining is found in the terminal ganglion
      and thoracic nerves. Codistribution of peripheral varicose fiber plexuses is
      regularly seen for amines and peptides, whereas the colocalization of substances
      in neurons has not been detected for any of the neuroactive compounds
      investigated. The varicose fiber system is regarded as complementary to the
      classical neurohemal organs.

PMID- 7621527
TI  - Ultrastructural study of periodic lamellar granules in human neutrophils.
AB  - Granules consisting of periodically arranged membranous lamellae and amorphous
      electron-opaque material, i.e., periodic lamellar granules, are present in human
      neutrophils. To date, no extensive ultrastructural studies have been carried out
      on these granules because of their infrequent presence in neutrophils. The bone
      marrow of 18 cases of chronic myeloproliferative disorders, including one case of
      chronic neutrophilic leukemia in which periodic lamellar granules were frequently
      seen in neutrophils, was investigated by electron microscopy. Periodic lamellar
      granules were seen in neutrophils in 12 of the 18 cases at varying frequencies.
      They were preferentially seen in immature neutrophils. The transverse profiles of
      these granules revealed concentric complete/incomplete rings or periodic parallel
      straight lines, i.e., various patterns of lamellar arrangement were present.
      Periodic lamellar granules were positive for myeloperoxidase and lysozyme at the
      electron-microscopic level. These results suggest that these granules represent a
      primary neutrophil granule subtype. However, their functional and pathologic
      significance remains unknown.

PMID- 7621525
TI  - Functional and structural interactions between osteoblastic and preosteoclastic
      cells in vitro.
AB  - Osteoblasts are involved in the bone resorption process by regulating osteoclast
      maturation and activity. In order to elucidate the mechanisms underlying
      osteoblast/preosteoclast cell interactions, we developed an in vitro model of co
      cultured human clonal cell lines of osteoclast precursors (FLG 29.1) and
      osteoblastic cells (Saos-2), and evaluated the migratory, adhesive, cytochemical,
      morphological, and biochemical properties of the co-cultured cells. In Boyden
      chemotactic chambers, FLG 29.1 cells exhibited a marked migratory response toward
      the Saos-2 cells. Moreover, they preferentially adhered to the osteoblastic
      monolayer. Direct co-culture of the two cell types induced: (1) positive staining
      for tartrate-resistant acid phosphatase in FLG 29.1 cells; (2) a decrease of the
      alkaline phosphatase activity expressed by Saos-2 cells; (3) the appearance of
      typical ultrastructural features of mature osteoclasts in FLG 29.1 cells; (4) the
      release into the culture medium of granulocyte-macrophage colony stimulating
      factor. The addition of parathyroid hormone to the co-culture further potentiated
      the differentiation of the preosteoclasts, the cells tending to fuse into large
      multinucleated elements. These in vitro interactions between osteoblasts and
      osteoclast precursors offer a new model for studying the mechanisms that control
      osteoclastogenesis in bone tissue.

PMID- 7621528
TI  - Rat intestinal galactoside-binding lectin L-36 functions as a structural protein
      in the superficial squamous cells of the esophageal epithelium.
AB  - Using an affinity purified antibody raised against the RI-H fragment of rat
      intestinal lectin L-36, the latter protein has been identified within the
      esophageal epithelium by means of ultracryotomy followed by immunogold labeling.
      The epithelium consists of 4 morphologically distinct cell-types, namely, the
      basal, spiny, granular and squamous cells, and each of these exhibits a different
      immunolabeling pattern. The basal cells form a layer on the basal lamina, and in
      these a diffuse cytoplasmic staining is observed. This basal cell layer is
      overlaid by spiny cells that extend many cell processes into wide intercellular
      spaces. In these cells, immunogold particles are found only on small granular
      inclusions consisting of an electron-lucent homogeneous substance. The granular
      cells form a third layer over the spiny cells, and are characterized by a number
      of large granular inclusions with an electron-dense core rimmed by a less
      electron-dense substance. Immunogold labeling is found on these granules, both on
      the core and peripheral region. Squamous cell-types constitute the most
      superficial layer of the epithelium. They are without granular inclusions, and
      immunogold labeling is confined to the cytoplasmic surface of the thickened
      plasma membrane. These findings suggest that L-36 is produced in the basal cells
      as free cytosolic protein, then becomes progressively aggregated into the
      granular inclusions of the spiny and granular cells, and is eventually
      transferred onto the cytoplasmic surface of the squamous cell plasma membrane
      where it may interact with complementary glycoconjugate(s) located at this
      site.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7621529
TI  - Specific immunocytochemical localization of cathepsin E at the ruffled border
      membrane of active osteoclasts.
AB  - The immunocytochemical localization of cathepsin E, a non-lysosomal aspartic
      proteinase, was investigated in rat osteoclasts using the monospecific antibody
      to this protein. At the light-microscopic level, the preferential
      immunoreactivity for cathepsin E was found at high levels in active osteoclasts
      in the physiological bone modeling process. Neighboring osteoblastic cells were
      devoid of its immunoreactivity. At the electron-microscopic level, cathepsin E
      was exclusively confined to the apical plasma membrane at the ruffled border of
      active osteoclasts and the eroded bone surface. Cathepsin E was also concentrated
      in some endocytotic vacuoles of various sizes in the vicinity of the ruffled
      border membrane, some of which appeared to be secondary lysosomes containing the
      phagocytosed materials. These results strongly suggest that this enzyme is
      involved both in the extracellular degradation of the bone organic matrix and in
      the intracellular breakdown of the ingested substances in osteoclasts.

PMID- 7621530
TI  - Differences in features of calcium transients between the nucleus and the cytosol
      in cultured heart muscle cells: analyzed by confocal microscopy.
AB  - We analyzed spatio-temporal characteristics of Ca2+ transients in the cytosol and
      the nucleus of cultured neonatal rat heart cells using confocal imaging with Indo
      1 and Fluo-3. In resting heart muscle cells, nuclear [Ca2+] was maintained lower
      than the cytosolic level. The rise in nuclear [Ca2+], during either E-C coupling
      or propagation of the Ca2+ wave, began at the edge of the nucleus in the
      immediate vicinity of the rise in global or localized cytosolic [Ca2+], and
      spread inwardly. The rise in [Ca2+] was slower and smaller in the nucleus than in
      the cytosol. The decay in [Ca2+] was also slower in the nucleus than the cytosol,
      thereby reversing the initial [Ca2+] gradient between them. Caffeine markedly
      enhanced the rise in nuclear [Ca2+] while maintaining inward spreading. The
      heterogeneity of nuclear Ca2+ transients during cellular contractilities suggests
      that influx of Ca2+ from perinuclear stores into the nucleus plays a predominant
      role in the nuclear [Ca2+] rise. The results also indicated that spatio-temporal
      characteristics of Ca2+ transients are quite different between the nucleus and
      the cytosol, thereby suggesting that they are differentially regulated in the
      nucleus and the cytosol.

PMID- 7621531
TI  - The regulation of leukotriene D4-induced calcium influx in human epithelial cells
      involves protein tyrosine phosphorylation.
AB  - Leukotriene D4 (LTD4) has been found to induce calcium signalling in the
      intestinal epithelial cell line Int 407, and this action involves the activation
      of both different GTP-binding proteins (G-proteins) and phospholipase C of the
      gamma-subtype (PLC-gamma). With this knowledge as the incentive, we investigated
      the possible regulatory role of protein tyrosine kinase activities in the calcium
      signalling system of the LTD4 receptor. The tyrosine kinase inhibitors genistein
      and herbimycin. A both reduced the LTD4-induced calcium signal by 70% when Int
      407 cells were stimulated in the presence of extracellular calcium, but had no
      effect on the signal when the cells were stimulated in a calcium-free medium. In
      accordance with these findings, pretreatment with a tyrosine kinase inhibitor
      also blocked thapsigargin-induced cellular influx of calcium. These inhibitors
      had no effect on the intracellular mobilisation of calcium, which was supported
      by the findings that LTD4 was able to induce an increase in the tyrosine
      phosphorylation of PLC-gamma even when one of the tyrosine kinase inhibitors was
      present. Of possible interest regarding the effect of genistein on LTD4-induced
      calcium influx is that two major tyrosine phosphorylated protein bands were
      detected in immunoprecipitates obtained with PLC-gamma antibodies from LTD4
      stimulated cells. These proteins, which associate with PLC-gamma, have estimated
      molecular weights of 84 and 97 kD. Preincubation with genistein completely
      abolished the LTD4-induced increase in tyrosine phosphorylation of the major 97
      kD band, whereas the 84 kD protein band, like the PLC-gamma band, still exhibited
      an increased phosphorylation of tyrosine residues in response to LTD4. Neither
      this effect nor any of the other effects of genistein were induced when cells
      were preincubated with daidzein, an inactive analogue of genistein. The present
      results suggest that LTD4-induced calcium signalling in epithelial cells involves
      not only tyrosine phosphorylation of PLC-gamma, but also a tyrosine kinase
      dependent step which occurs downstream of PLC-gamma activation and is directly
      implicated in the regulation of agonist-mediated calcium influx.

PMID- 7621532
TI  - Receptor-mediated calcium signals in astroglia: multiple receptors, common stores
      and all-or-nothing responses.
AB  - Calcium signals following activation of P2Y purinergic, alpha 1 adrenergic, and
      muscarinic cholinergic receptors were examined in individual astroglial cells.
      ATP, phenylephrine and carbachol, each increased intracellular calcium levels
      ([Ca2+]i) to similar amplitudes in the presence or absence of extracellular Ca2+.
      The dose-response relationship showed that less than an order of magnitude
      increase in ligand concentration led to maximal increase in [Ca2+]i from basal
      levels. Simultaneous application of multiple ligands did not produce additive
      effects on [Ca2+]i. These data suggested that different ligands released Ca2+
      from common stores and that each of the ligands could cause maximal release.
      Application of a second ligand immediately after the first ligand produced an
      additional Ca2+ rise, suggesting that the Ca2+ stores were rapidly refilled and
      that receptor desensitization rather than Ca2+ depletion accounted for the rapid
      decline of the Ca2+ peak. Caged IP3 produced Ca2+ signals similar to those
      produced by ligands. For a given cell, both caged IP3 and ligands sometimes
      produced only one level of partial Ca2+ increases, suggesting the presence of a
      pool of high IP3-sensitive stores. Together, our results indicate that
      neuroligands tend to generate an all-or-nothing Ca2+ release from IP3 sensitive
      stores. The interactions between different receptor systems most likely occur at
      the level of IP3 accumulation.

PMID- 7621533
TI  - Changes in Ca2+ concentration in phorbol ester and thapsigargin treated glioma C6
      cells. The role of protein kinase C in regulation of Ca2+ entry.
AB  - Glioma C6 cells treated with 12-0-tetradecanoyl-phorbol-13-acetate, TPA (10 nM
      and 100 nM) manifested slow increase in intracellular calcium concentration
      ([Ca2+]i), dependent upon both Ca2+ release from intracellular stores and Ca2+
      entry, and ranging from 50 to 500 nM in different cells. The effect of TPA was
      abolished by the down-regulation procedure and by protein kinase C inhibitors,
      such as staurosporine (100 nM), suramin (100 microM), and sphingosine (100
      microM), pointing to a role of protein kinase C (PKC) in this process. On the
      other hand, thapsigargin (100 nM), a selective inhibitor of the endoplasmic
      reticulum Ca(2+)-ATPase, produced a rapid increase in [Ca2+]i (up to 800 nM).
      This increase consisted of a transient initial phase followed by sustained
      elevation in [Ca2+]i, typical of Ca2+ release from intracellular stores and of
      Ca2+ entry, respectively. However, when the cells were exposed to TPA (100 nM)
      prior to thapsigargin (100 nM), then thapsigargin produced only a transient rise
      in [Ca2+]i. We suggest that TPA, a PKC activator, affects thapsigargin-induced
      Ca2+ entry, probably by PKC-mediated changes in cytoskeleton structures.

PMID- 7621534
TI  - Chaos in intracellular Ca2+ oscillations in a new model for non-excitable cells.
AB  - A new model for intracellular Ca2+ oscillations is presented. The new model
      reinterprets two previous models, the ICC and CICR mechanisms, and incorporates
      the bell-shaped dependence of Ca2+ release on cytosolic [Ca2+]. Complex
      oscillations and chaos are found with this new model, confirming experimental
      observations of complex oscillations. A rich bifurcation sequence is found for
      the model as the stimulation due to agonist (R) is varied, including a period
      doubling route to chaos and a period-adding sequence of mixed-mode states.

PMID- 7621535
TI  - Nuclear calmodulin responds rapidly to calcium influx at the plasmalemma.
AB  - We have studied the rate and extent of calcium binding to calmodulin in neuronal
      cytosol and nucleus during brief calcium influx across the plasmalemma. Rat
      sensory neurones were whole-cell patch clamped using a pipette containing a
      fluorescent analogue of calmodulin that reports when it has bound calcium.
      Cytosolic and nuclear signals were separated using a confocal microscope.
      Plasmalemmal calcium influx during a one second depolarization that activated L
      type calcium channels caused large fractions of calmodulin in both the cytosol
      and nucleus to bind calcium. Thus, contrary to previous predictions, nuclear
      processes that require the calcium:calmodulin complex will be activated readily
      by even brief cell stimulation.

PMID- 7621536
TI  - Primary stent deployment in occlusive subclavian artery disease.
AB  - Primary (without antecedent balloon dilation) Palmaz stent implantation was
      successfully performed in 27 consecutive patients entering with 31 obstructed
      subclavian arteries. Stents (n = 50) were successfully deployed, using the
      brachial (n = 7), femoral (n = 16), or combined (n = 8) approach, to
      revascularize 31 subclavian vessels [8 occluded (26%); 23 stenotic (74%)], using
      a 6 or 7.5 French delivery system. The indications for intervention were arm
      claudication in 8 patients (30%), subclavian steal syndrome in 11 patients (41%),
      angina pectoris secondary to impaired blood flow to the left internal mammary
      artery coronary bypass in 6 patients (22%), and recanalization of a left
      subclavian occlusion to permit central arterial access and performance of a
      second interventional procedure 2 patients (7%). The percent diameter stenosis
      improved from 85 +/- 12% to 6 +/- 7% (P < 0.001); and, the peak and mean
      translesion gradients decreased, respectively, from 56 +/- 35 mm Hg to 3 +/- 4 mm
      Hg (P < 0.01), and 29 +/- 18 mm Hg to 2 +/- 2 mm Hg (P < 0.01). Procedural
      complications encountered were one stent dislodgement with migration into and
      uneventful deployment within the right external iliac artery, and two brachial
      artery repairs. No acute vessel closures, deaths, myocardial infarctions,
      cerebrovascular accidents, transient ischemic attacks, or need for transfusions
      occurred. Therefore, primary subclavian artery stent deployment can be performed
      using low-profile sheath systems with excellent success (100%), resulting in
      immediate restoration of pulsatile flow, and few complications. The incidence of
      lesion recurrence remains for follow-up studies.

PMID- 7621537
TI  - Patient selection reduces thrombotic complications of emergent stenting for
      failed PTCA.
AB  - A comparison of consecutive initial and later patients receiving emergent
      coronary artery stents to salvage failed PTCA procedures was made to determine
      whether experience with this procedure can improve patient outcome. Twenty-six
      consecutive patients underwent emergent, unplanned implantation of one or more
      Palmaz-Schatz coronary stents at our institution over a 3-1/2 year period.
      Indications for stent insertion included impending vessel closure (decrease in
      TIMI flow grade and clinical evidence of ischemia) or acute occlusion (TIMI flow
      grade 0 or 1 and > or = 99% stenosis) after PTCA. Immediate and final success (30
      day) were determined, and the results in the first (Initial) 13 patients were
      compared to the remaining (Later) 13 patients. Baseline characteristics of the
      study population included a male predominance (69%) with a mean (+/- SD) age of
      57 +/- 10 years. Conventional balloon PTCA was performed in all three native
      coronary arteries with an increase in mean percentage stenosis from 76 +/- 13 to
      85 +/- 14% (P < 0.05). Twelve patients developed acute occlusion and 14 patients
      impending closure after PTCA due to the appearance of thrombus (12%), dissection
      (46%), or both (35%). Palmaz-Schatz stents were successfully inserted in all
      patients restoring TIMI grade 3 antegrade flow; however, major complications
      developed in almost 50% of patients. Comparison of initial and later patients
      showed no differences in demographic or pre-PTCA angiographic characteristics.
      Later patients had less severe stenoses post-PTCA (before stenting) and were less
      likely to have thrombus present at the angioplasty site (15% vs. 77%, P <
      0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7621538
TI  - Comparative analysis of saphenous vein bypass vs. native coronary artery balloon
      angioplasty: technical differences and angiographic response.
AB  - To evaluate technical differences and angiographic response of saphenous vein
      bypass graft angioplasty in comparison to native coronary arteries, we
      retrospectively analyzed 54 patients undergoing this procedure at The Toronto
      Hospital between February 1988 and May 1993. These subjects were temporally
      matched to a cohort of successful native coronary angioplasties, with comparison
      of technical parameters, pre-existing qualitative/quantitative (Cardiac
      Measurement System) stenotic morphology, and angiographic response; including
      changes in minimum lumen diameter. Saphenous bypass graft angioplasty utilized
      larger balloons (CABG, 3.27 +/- 0.65 vs. native, 2.90 +/- 0.37 mm, P < .05), and
      higher inflation pressures (CABG, 10.1 +/- 3.7 vs. native, 8.8 +/- 2.5 atm, P <
      .05), although in a relative sense, balloon/artery ratios were similar (CABG,
      1.09 +/- 0.20 vs. native, 1.03 +/- 0.15, pNS). Pre-procedural bypass graft
      lesions were more complex, with more frequent ACC/AHA type B1 lesions [CABG,
      24/54 (44%) vs. native, 16/54 (30%), P < .05] and luminal thrombus [CABG, 17/54
      (31%) vs. native, 6/54 (11%), P < .05]. Quantitative angiography revealed larger
      "reference" diameters within saphenous veins (CABG, 3.41 +/- 0.76 vs. native,
      3.04 +/- 0.51 mm, P < .05), although minimum lumen diameter was less severe
      (CABG, 0.83 +/- 0.41 vs. native, 0.77 +/- 0.36, P < .05). In terms of balloon
      angioplasty response, greater improvement in luminal diameter was seen in bypass
      graft lesions (CABG, 1.55 +/- 0.53 vs. native, 1.32 +/- 0.44 mm, P < .05), with
      the largest changes within the "body" of the saphenous vein (ostial, 1.53 +/-
      0.37; body, 1.68 +/- 0.50; anastomosis, 1.37 +/- 0.57 mm).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7621539
TI  - Maximal myocardial perfusion by videodensitometry in the assessment of the early
      and late results of coronary angioplasty: relationship with coronary artery
      measurements and left ventricular function at rest.
AB  - In the assessment of the acute results of percutaneous transluminal coronary
      angioplasty (PTCA), myocardial perfusion at maximal vasodilatation theoretically
      has fewer limitations than the coronary flow reserve measurements and
      quantitative coronary angiography. The purpose of this study was to compare the
      myocardial perfusion to the measurements of the severity of the lesion (minimal
      luminal diameter and percent area stenosis) and to relate it to the changes of
      left ventricular function after PTCA. Regional myocardial perfusion was assessed
      during intracoronary papaverine, using the inverse mean transit time of contrast
      medium (1/Tmn), before, 15 min after, 18-24 hr after, and 6 months after
      successful single-vessel PTCA in 14 patients with stable angina. Left ventricular
      angiography (before angioplasty, 18-24 hr after, and 6 months later) was analysed
      by area-length and centerline methods. Immediately after PTCA, 1/Tmn increased
      from 0.14 +/- 0.07 sec-1 to 0.21 +/- 0.09 sec-1 (P = .001). Maximal myocardial
      perfusion remained higher than the pre-PTCA value the day after angioplasty
      (1/Tmn of 0.23 +/- 0.09 sec-1), while it reduced to near pre-PTCA values at
      follow-up (1/Tmn of 0.16 +/- 0.05 sec-1). Before PTCA, three out of ten patients
      had ejection fraction of < 65%, and seven had mild-to-moderate hypokinesis. The
      day after PTCA the ejection fraction and the regional dysfunction improved
      significantly. The change in ejection fraction 18-24 hr after PTCA did not
      correlate with minimal luminal diameter and percent area stenosis and correlated
      slightly with the improvement of perfusion (r = 0.54, P = .10). At follow-up left
      ventricular function deteriorated in the whole group, despite the persistence of
      angiographic success of PTCA, possibly because of changes in the loading
      condition. Coronary artery stenosis measurements and 1/Tmn failed to correlate
      with the left ventricular function. Given the difficulties in routine application
      of the analysis of time-density curves, the measurement of minimal luminal
      diameter remains a more practical assessment of the results of the intervention.
      However, the improvement of myocardial perfusion may give more information than
      coronary artery dimensions of the early recovery of left ventricular function.

PMID- 7621540
TI  - Subclavian artery dissection during diagnostic cardiac catheterization: the role
      of conservative management.
AB  - Dissection of the subclavian artery during routine cardiac catheterization while
      obtaining cannulation to the left internal mammary artery is an unusual
      complication and to our knowledge has never been reported. Conservative
      management of this vascular injury can avoid the sequelae of high-risk surgical
      repairs made difficult by a complex operative exposure. We describe a case in
      which dissection of the left subclavian artery was treated conservatively with an
      excellent outcome.

PMID- 7621541
TI  - Catheter-induced "accordion effect" in tortuous right external iliac artery
      during peripheral angiography.
AB  - Mechanical distortion of tortuous coronary arteries mimicking spasm or dissection
      during percutaneous transluminal coronary angioplasty due to balloon guidewire
      systems has previously been reported. This case reports a similar phenomenon in
      the peripheral vascular system induced by a diagnostic catheter. Recognition of
      this pseudo lesion may help to avoid complications and unnecessary intervention.

PMID- 7621542
TI  - Right ventricular infarction following percutaneous coronary rotational
      atherectomy.
AB  - We describe a case of right ventricular infarction complicating percutaneous
      coronary rotational atherectomy of sequential calcified right coronary artery
      lesions. Right ventricular infarction resulted from occlusion of two right
      ventricular marginal branches during successful atherectomy of the right coronary
      artery.

PMID- 7621543
TI  - Aneurysm of saphenous vein graft to coronary artery presenting as non-Q-wave
      myocardial infarction secondary to mass effect.
AB  - Large aneurysms (> 4 cm) of saphenous vein grafts (SVG) to coronary arteries are
      a rare complication of coronary artery bypass graft surgery (CABG). A 64-year-old
      male, status post-CABG 14 years ago, presented with dyspnea and diaphoresis.
      Pneumonia and non-Q-wave myocardial infarction (MI) were diagnosed. Cardiac
      catheterization and chest computed tomography demonstrated a 5 x 7-cm aneurysm of
      a SVG. At the time of surgery, the left internal mammary artery (grafted to the
      left anterior descending artery) was found to be stretched tautly over the
      aneurysm, resulting in impaired flow. The aneurysm was successfully resected.
      This is the first published case implicating a SVG aneurysm as the direct cause
      of a MI by mass effect.

PMID- 7621544
TI  - Myocardial bridging involving more than one site of the left anterior descending
      coronary artery: an uncommon cause of acute ischemic syndrome.
AB  - An infrequent angiographic finding is reported of myocardial bridging involving
      more than one site of the left anterior descending coronary artery in a
      symptomatic patient with ischemia exacerbated by nitroglycerin administration.
      Beta-blocker therapy alone was followed by a favorable long-term outcome.

PMID- 7621545
TI  - Aneurysm of the aortic sinus of Valsalva with reversed shunt of ductus
      arteriosus.
AB  - A rare case of aneurysm of aortic sinus of Valsalva associated with patent ductus
      arteriosus and Eisenmenger's syndrome in a 7-yr-old boy is described. The
      diagnosis was made by echocardiography and cardiac angiography.

PMID- 7621546
TI  - Interventional physiology. Part XVI: normal coronary flow velocity patterns:
      considerations of artifacts, arrhythmias, and anomalies.
AB  - During normal flow velocity recording, various physiologic or technical problems
      may appear which can produce confusing flow signals. This section of
      Interventional Physiology reviews the patterns of normal coronary flow velocity
      and examines several artifacts and other features encountered in clinical
      practice. Recognition of these variations will help the interventional
      cardiologist to differentiate between physiologic and pathologic events.

PMID- 7621547
TI  - Backup wire for difficult coronary angiography.

PMID- 7621548
TI  - Balloon catheter retrieval of dislodged coronary artery stents: a novel
      technique.
AB  - Potential complications of intracoronary stenting include stent dislodgement and
      embolization. We describe a patient in whom a stent was dislodged from a coronary
      balloon catheter to the iliac artery. A peripheral angioplasty balloon was used
      to withdraw the stent into the arterial sheath and thereby remove it from the
      patient.

PMID- 7621549
TI  - Techniques for Palmaz-Schatz stent deployment in lesions with a large side
      branch.
AB  - Palmaz-Schatz coronary stent implantation in lesions with a large side branch are
      reported. The first case describes how to manage plaque shifting after stent
      implantation. The second and third cases demonstrate a kissing balloon
      predilatation and stent dilatation technique of a bifurcational lesion. The final
      case demonstrates a stent implantation technique through the stent struts of a
      previously deployed stent.

PMID- 7621550
TI  - Usefulness of interlocking detachable coil for embolization of the major aorto
      pulmonary collateral artery: a case report.
AB  - A 5-yr-old male had undergone a right-modified Blalock-Taussig shunt operation at
      the age of 1 mo for stenotic patient ductus arteriosus and pulmonary atresia with
      ventricular septal defect. Before a corrective operation, the angiogram revealed
      one large major aorto-pulmonary collateral artery from the descending aorta to
      the right upper lung. Embolization of the major aorto-pulmonary collateral artery
      was successfully performed using interlocking detachable coils. This is the first
      reported case of embolization of the major aorto-pulmonary collateral artery
      using this device.

PMID- 7621551
TI  - Simultaneous inflation of tandem (sequential) angioplasty balloons: a means of
      simultaneously treating multiple lesions in one coronary artery.
AB  - We report a novel approach to dilating multiple lesions in a coronary artery.
      Through the same guide and over different wires, a 3.5 mm diameter, 20 mm length,
      and a 3.0 mm diameter, 90 mm length balloon were simultaneously inflated in a
      right coronary artery. This approach, which simultaneously treats sequential
      (tandem) lesions of different diameter and length, allows reduction of both the
      total duration of ischemia and procedural time and may improve early angiographic
      outcome.

PMID- 7621552
TI  - Hugging balloon angioplasty of right coronary artery.
AB  - We report a case of "hugging balloon" dilatation of a giant right coronary artery
      using two dilatation catheters, a balloon "on a wire" and a balloon "rapid
      exchange" systems via a single guiding catheter. The necessity of larger PTCA
      balloon catheter (> 4.0 mm) was stressed.

PMID- 7621553
TI  - Guide catheter exchange.

PMID- 7621554
TI  - Origin of an anomalous right coronary artery: anterior or posterior ascending
      thoracic aorta.

PMID- 7621555
TI  - Comment on "Editorial comment" from Masakiyo Nobuyoshi, M.D., Cathet Cardiovasc
      Diagn 33:156(1994)

PMID- 7621556
TI  - Do mothers and fathers interact differently with their child or is it the
      situation which matters?
AB  - This study aimed to test the Differential Experience Hypothesis which suggests
      mothers and fathers interact differently with their child. The forms and
      functions of parents' language in interaction with their 2-2.5-year-old child
      were investigated across four different interactional settings within the home
      and for each parent separately. The results, supporting the differential
      experience hypothesis, suggest that differences do exist between mothers' and
      fathers' conversational styles. However, the findings indicate that gender is not
      the only influencing factor. The situations in which interaction occurs also
      appear to have an effect on the style of interaction irrespective of the sex of
      the parent (context hypothesis).

PMID- 7621557
TI  - Post-traumatic stress symptoms in children and parents following a school-based
      fatality.
AB  - In 1991 the roof blew off a Swindon Primary School. One child was killed. Two
      years later 19 of her classmates were interviewed. The parent who collected the
      child from school that day was also interviewed. Recalled levels of post
      traumatic stress syndrome (PTSD) symptoms were assessed in both parent and child
      in the month following the incident. The children's symptom levels at 2 years
      were also assessed. Parents and children recalled significant post-traumatic
      stress reactions at 1 month. The level of symptoms in parents did not correlate
      with that of their own children.

PMID- 7621558
TI  - Personal health record for school children with multiple needs.
AB  - Children with severe learning difficulties in special schools often have multiple
      physical disabilities. Their case notes are frequently bulky. Many professionals
      are involved in their care and information on the child is seldom readily
      available or accessible. A concise, regularly updated Personal Health Record
      given to the child or carer would overcome these problems and allow for timely
      and appropriate care to be provided.

PMID- 7621559
TI  - Family involvement in multidisciplinary team evaluation: professional and parent
      perspectives.
AB  - For many children and families, a multidisciplinary team evaluation is their
      introduction to special education systems. Increasingly, federal guidelines
      mandating parent involvement in all aspects of service provision have meant that
      parents are being asked to participate as part of the evaluation team. If
      families and professionals are to serve as partners in the evaluation process,
      mutual respect and understanding of one another's perspectives will be crucial.
      This paper uses survey data from 39 parents and 81 professionals to examine the
      various expectations and perceptions brought by participants to the assessment
      process. Results indicated that there is substantial variability of perceptions
      among parents and professionals about the nature of child assessment and their
      respective roles in it. Implications for research and practice are discussed,
      along with techniques for involving families in the assessment process in more
      meaningful ways.

PMID- 7621560
TI  - An audit of oestradiol levels and implant frequency in women undergoing
      subcutaneous implant therapy.
AB  - OBJECTIVES: The aim of the study was to review our long-term use of subcutaneous
      oestradiol (E2) implant therapy for the treatment of climacteric symptoms in post
      menopausal women. On the grounds that the aim is to restore premenopausal serum
      E2 levels, our declared clinical policy is not to repeat implants even in the
      presence of symptoms if serum E2 levels are > 400 pmol/l. Therapy was with 50 mg
      E2 implants inserted subcutaneously in the lower abdominal wall. DESIGN: All
      women who had attended the gynaecological/endocrinological clinic who had
      received subcutaneous E2 implants for the relief of climacteric symptoms between
      December 1981 and 1992 were included. RESULTS: Between December 1981 and December
      1992, 275 women received a total of 759 50 mg E2 implants. The median length of
      implant therapy was 34.2 months (range 3.7-109.5 months), and the median number
      of implants per patient was 4 and ranged from 1 to 13. One hundred and twenty
      nine women had more than four implants and their mean recorded serum E2 level was
      425 +/- 187 (mean +/- SD) pmol/l; the mean level over the first 24 months of
      therapy was 408 +/- 157 pmol/l. This was not different from the mean value of the
      remaining period of therapy (439 +/- 168 pmol/l). Following the second implant
      there was no significant progressive rise in serum E2 with time and implant
      number and the mean E2 level per patient was no higher in those patients who
      received implants more frequently. The mean time between the first two implants
      was 9.7 +/- 0.4 months and between subsequent ones was 11.7 +/- 0.5 months. After
      the first two implants there was no progressive change in this interval with
      time. CONCLUSION: This study shows that effective, safe and sympathetic
      management of women with oestrogen deficient symptoms may be achieved by use of
      two criteria to determine re-treatment; the return of symptoms, and a serum E2
      level no higher than 400 pmol/l. Once therapy is established, E2 implants may
      need to be prescribed only on an annual basis. There appears to be no
      justification for giving E2 implants more frequently as this policy achieves
      satisfactory (physiological) premenopausal E2 levels and good symptomatic relief
      without any evidence for accumulation of E2 or 'tachyphylaxis'.

PMID- 7621561
TI  - Should serum calcitonin be measured routinely in all patients with nodular
      thyroid disease?

PMID- 7621563
TI  - Adrenarche does not occur in treated patients with congenital adrenal hyperplasia
      resulting from 21-hydroxylase deficiency.
AB  - OBJECTIVE: There have been few studies of adrenarche in patients with congenital
      adrenal hyperplasia (CAH). We have therefore sought to detect the onset of
      adrenarche in CAH patients and to investigate whether its evolution was
      influenced by the severity of the disease, the age at the onset of substitution
      therapy, or both. DESIGN AND PATIENTS: Sixteen female CAH patients were studied
      longitudinally for 4-11 years. They were all given substitution therapy and
      treatments were well controlled as judged by repeated hormonal evaluations. The
      patients were divided into two groups: group A consisted of 10 girls with a
      severe classic (congenital) form, while group B included 6 girls presenting with
      a non-classic form. MEASUREMENTS: Circulating levels of dehydroepiandrosterone
      sulphate (DHEAS), were determined as an indicator of adrenarche. Hormonal
      assessments included measurements of 17-hydroxyprogesterone (17-OHP),
      testosterone, ACTH and plasma renin activity. All were estimated by conventional
      specific assays. RESULTS: Mean levels were analysed in consecutive two-year age
      periods. In group A, DHEAS levels were significantly lower at any age than in
      control subjects, and lower than in patients with non-classic CAH. DHEAS levels
      showed no increment with age. In group B, plasma DHEAS levels were surprisingly
      high for the age at the time of diagnosis, declining gradually on substitution
      therapy, although they remained somewhat higher than in group A. CONCLUSIONS: The
      high DHEAS levels observed in untreated girls of group B are probably the result
      of chronic hypersecretion of ACTH. Under well controlled, non-suppressive
      substitution therapy, patients with congenital adrenal hyperplasia showed no rise
      in DHEAS levels at the physiological age of adrenarche whatever the degree of the
      enzyme defect and whatever the age at onset of therapy.

PMID- 7621562
TI  - Prevalence of sporadic medullary thyroid carcinoma: the importance of routine
      measurement of serum calcitonin in the diagnostic evaluation of thyroid nodules.
AB  - OBJECTIVE: The prevalence of sporadic forms of medullary thyroid carcinoma (MTC)
      has been studied in patients living in an area of moderate iodine deficiency.
      Such forms of MTC are usually diagnosed after surgery and have little chance of
      definitive cure. Using the measurement of basal serum calcitonin (CT) levels in a
      large series of patients with both thyroid disease and normal 24-hour urinary
      iodine excretion, we assessed the prevalence of MTC and, in patients affected
      with the disease, we also evaluated the stage of the disease according to
      surgical findings and post surgical plasma CT levels. PATIENTS: A prospective
      study of 657 patients with thyroid disease (469 with nodular and 188 with non
      nodular thyroid disease). As controls, 40 normal subjects were also studied.
      MEASUREMENTS: In all patients: (1) measurement of basal serum CT, free T4, total
      T3, TSH levels and serum TSH-receptor, peroxidase and thyroglobulin (Tg) antibody
      concentrations, (2) thyroid ultrasonography, (3) fine needle aspiration cytology
      (FNAC). In patients with increased basal CT levels: (1) measurement of serum CT
      levels during pentagastrin test prior to surgery, (2) histological examination
      and immunostaining with both anti-CT and anti-Tg antibodies of all the nodular
      thyroid tissue surgically removed, (3) measurement of basal and pentagastrin
      stimulated serum CT values after surgery. RESULTS: All the patients with non
      nodular thyroid disease had normal basal CT levels. Four patients (0.84%) with
      nodular thyroid disease (2 with uninodular and 2 with multinodular goitre) had
      both elevated basal and pentagastrin stimulated CT levels. In the two patients
      with uninodular goitre, FNAC was suggestive of MTC in 1 (nodular diameter 8.0 cm)
      and of follicular carcinoma in 1 (nodular diameter 2.5 cm). Histological
      examination of the nodules confirmed these histotypes. Immunostaining with anti
      CT antibodies was positive in the former patient but also in the latter. FNAC was
      suggestive of benign adenomatous tissues in the two patients with multinodular
      goitre. Histological examination of all the thyroid nodules confirmed the
      cytological findings. However, serial sections through the gland in each of these
      two patients showed an occult follicular carcinoma which had, however, positive
      staining with anti-CT antibodies. Furthermore, immunostaining with anti-Tg
      antibodies was negative in the patient with MTC but positive in the 3 patients
      with follicular carcinoma. Finally, both basal and pentagastrin stimulated CT
      levels remained elevated after total thyroidectomy only in the patient with FNAC
      suggesting MTC. CONCLUSIONS: This study demonstrates a surprisingly high
      prevalence of sporadic forms of medullary thyroid carcinoma in patients with
      nodular thyroid disease. Such forms of medullary thyroid carcinoma seem to be
      unrelated to iodine intake and may be pure or mixed with a follicular carcinoma.
      In these mixed thyroid carcinomas, only the neoplastic follicular pattern was
      seen on both cytological and histological examination. Routine measurements of
      serum calcitonin levels should therefore be considered an integral part of the
      diagnostic evaluation of thyroid nodules. Indeed, increasing the accuracy of
      diagnosis of medullary thyroid carcinoma encourages the surgeon to perform more
      radical treatment, thus achieving more frequent normalization of post-operative
      serum calcitonin levels.

PMID- 7621564
TI  - Hypothalamic-pituitary dysfunction in patients with craniopharyngioma.
AB  - OBJECTIVE: Previous studies of preoperative pituitary function in patients with
      craniopharyngioma have been limited in scope and have focused on children. We
      have evaluated the impact of craniopharyngiomas and their surgical treatment on
      pituitary function in a large group of mostly adult patients. DESIGN: We
      performed a retrospective study of patients treated at our centre between 1980
      and 1992. PATIENTS: Twenty-two men and 13 women, most of them adults, treated
      surgically for craniopharyngioma during the above period. MEASUREMENTS: Serum
      glucose, GH, LH, FSH, TSH and cortisol were measured both before and after a
      combined insulin induced hypoglycaemia, GnRH and TRH test. Basal concentrations
      of thyroid hormones, PRL and gonadal steroids were also measured. Preoperative
      computed tomographic scan was performed in all patients, and a detailed study of
      visual function before and after surgery was available for 32 of them. Endocrine
      function was reevaluated post-operatively. RESULTS: In preoperative studies, 29
      patients had some anterior pituitary deficit and 13 had diabetes insipidus. The
      most common abnormality was gonadotrophin deficiency, followed by GH deficiency.
      Dynamic studies suggested a hypothalamic origin for these deficits. In post
      surgical evaluation, impaired pituitary function was observed in most patients.
      Panhypopituitarism was present in 28 cases and diabetes insipidus in 24.
      CONCLUSIONS: Our report illustrates the high incidence of endocrine deficits in
      patients with craniopharyngioma. Additional hypothalamic-pituitary dysfunction
      usually occurs following surgical treatment of these tumours.

PMID- 7621566
TI  - Familial prolactinoma.
AB  - BACKGROUND: Apart from the rare association with type I multiple endocrine
      neoplasia (MEN-1), familial types of prolactinoma have not been reported.
      PATIENTS AND MEASUREMENTS: Eight hyperprolactinaemic patients in four families
      and 18 of their first and second-degree relatives (parents, children and
      grandchildren) were examined. Hormone levels were measured, as well as other
      biochemical parameters. RESULTS: Prolactinoma was diagnosed in more than one
      member of each of the four families. CONCLUSION: Familial prolactinoma is a
      distinct entity which is probably due to a genetic mutation promoting lactotroph
      proliferation.

PMID- 7621568
TI  - Changes in bone mass and metabolism after surgery for primary
      hyperparathyroidism.
AB  - BACKGROUND AND OBJECTIVE: Bone mass is often reduced in patients with primary
      hyperparathyroidism (pHPT) and is usually partially reversible after
      parathyroidectomy. However, site specific and overall skeletal benefits of
      surgery in mild asymptomatic pHPT remain uncertain. DESIGN: Cross-sectional and
      longitudinal studies. PATIENTS: Fourteen patients (12 women and 2 men) with pHPT.
      MEASUREMENTS: Baseline bone mass was assessed at the lumbar spine, left hip and
      whole body using dual-energy X-ray absorptiometry, and at the left os calcis
      using broad-band ultrasound attenuation. Changes in bone mass, serum intact PTH
      and osteocalcin, and urinary pyridinium cross-link excretion were recorded in 10
      patients followed for 6 months after surgery. RESULTS: (1) Cross-sectional study:
      Baseline measurements at the lumbar spine and hip were inversely related to both
      the serum PTH concentration and the weight of the parathyroid gland removed at
      surgery. (2) Longitudinal study: Six months after adenectomy, bone mass had
      increased significantly at the femoral neck, greater trochanter, whole body and
      os calcis, but not at the lumbar spine or Ward's area. Serum PTH, osteocalcin and
      pyridinium cross-link excretion all fell significantly after surgery. The
      percentage increment in whole body bone mineral content at 6 months was
      proportional to the baseline PTH. CONCLUSION: In primary hyperparathyroidism,
      preoperative reductions and post-operative gains in bone mass are proportional to
      the initial serum PTH concentration. Mild primary hyperparathyroidism probably
      does not cause appreciable bone loss at clinically relevant fracture sites such
      as the spine and hip, and in such cases the overall skeletal benefits of surgery
      are likely to be negligible.

PMID- 7621565
TI  - Gonadotrophin and gonadal steroid response to a single dose of a long-acting
      agonist of gonadotrophin-releasing hormone in ovulatory and anovulatory women
      with polycystic ovary syndrome.
AB  - OBJECTIVE: A previously published study has identified that anovulatory women
      with PCOS have an increased response of 17 alpha-hydroxyprogesterone (17OHP) and
      androstenedione to a GnRH analogue suggesting dysregulation of cytochrome P450c17
      alpha. The object of this study was to compare the responses of the pituitary
      ovarian axis to a single dose of a long-acting GnRH agonist (GnRHa) in both
      ovulatory and anovulatory women with PCOS with those in normal subjects. DESIGN:
      Comparative study of responses of LH, FSH and ovarian steroids to buserelin and
      the adrenal steroid response to synthetic ACTH in two groups of women with
      hyperandrogenaemia and polycystic ovaries: those with anovulatory menses or
      amenorrhoea and those with equally elevated serum testosterone concentrations but
      regular menses. Results in both groups of women with PCO were compared with those
      in normal subjects. SUBJECTS AND METHODS: Twenty-four women with hyperandrogenism
      and PCO (14 had oligo or amenorrhoea, 10 regular cycles) and 12 weight matched
      controls with normal ovaries, regular cycles and neither clinical nor biochemical
      evidence of hyperandrogenism. Subjects were given synthetic ACTH (Synacthen) 250
      micrograms i.v. on day 1 of the study and blood collected at 30 and 60 minutes
      thereafter. On the evening of day 1, dexamethasone treatment was commenced to
      suppress adrenal androgens. GnRHa 100 micrograms s.c. was given on day 2 and
      blood samples collected at 30-minute intervals for 4 hours and once more at 24
      hours after the injection. RESULTS: The acute responses of both immunoactive and
      bioactive LH to GnRHa were significantly greater in the ovulatory PCO group
      (ovPCO) than controls but the response was greater in anovulatory women with
      polycystic ovaries (anovPCO) than in either ovPCO or controls, throughout the 24
      hour study period. Despite the discrepancy in LH concentrations, basal serum
      concentrations of androstenedione were equally elevated in anovulatory and
      ovulatory women with PCO, compared with controls. There was a small but
      significant increase in androstenedione following GnRHa in both PCO groups at 24
      hours but not in controls. A similar pattern was observed in the response of
      17OHP to GnRHa although the response was significantly higher than controls in
      anovPCO women only. By contrast, the responses of both androstenedione and 17OHP
      to 250 micrograms synthetic ACTH were similar in PCO women to those in controls.
      CONCLUSIONS: These data provide evidence for ovarian hypersecretion of androgens
      in ovulatory, as well as anovulatory women with PCO, supporting the concept of
      abnormal regulation of 17-hydroxylase and (17,20-lyase activity in the ovary. The
      finding of an equal degree of hyperandrogenaemia in ovPCO and anovPCO groups,
      even though LH levels were much higher in the latter, suggests that
      hypersecretion of LH is not the primary cause of ovarian hyperandrogenism.
      Hyperandrogenism in PCOs may therefore represent an intrinsic abnormality of
      ovarian theca-interstitial cell function.

PMID- 7621567
TI  - Prolactin receptors in human pituitary adenomas.
AB  - OBJECTIVE: In the rat, prolactin receptors (PRL-R) have been identified in normal
      pituitary cells and in anterior pituitary tumours induced by oestradiol. No
      published data are available concerning PRL-R in the human pituitary. The aim of
      our study was therefore to detect the presence of PRL-R in the normal human
      pituitary gland and human pituitary adenomas. DESIGN: Evaluation of free and
      total PRL-R in the normal pituitary gland and different pituitary tumours
      characterized by immunocytochemical analysis. PATIENTS: Twenty-six unselected
      patients (14 M, 12 F) who underwent surgery for pituitary adenoma (3
      prolactinomas, 4 GH-PRL adenomas, 5 GH adenomas, 1 ACTH adenoma, 9 glycoprotein
      and/or alpha-subunit adenomas, 4 null cells adenomas) were studied. Nine
      pituitaries from subjects whose death was unrelated to brain and endocrine
      diseases, were also studied as a control group in the PRL binding studies.
      MEASUREMENTS: Free PRL-R in microsomal membranes were determined by in-vitro
      radioreceptor assay using 125I-labelled human PRL as ligand. Total PRL-R were
      also measured in the same membrane fractions by removing endogenous PRL bound to
      its receptors using 4 M MgCl2. Serum PRL levels were also evaluated in all
      patients before surgery using an IRMA method. RESULTS: Specific binding values
      for PRL (free PRL-R) were 0.39 +/- 0.03% (range 0-1.96%) in the pituitary
      adenomas. These binding values were identical to those observed in normal
      pituitaries (0.38 +/- 0.07%, range 0.1-0.78%). Elevated PRL binding (1.25% and
      1.96%) was found in two patients with PRL secreting adenomas and very high serum
      PRL levels (5768 and 11240 mU/I. No PRL binding was shown in 4 patients.
      Treatment of membranes with 4 M MgCl2 increased the specific binding (total PRL
      R) in both pituitary tumours (0.5 +/- 0.11%; P < 0.001) and normal pituitaries
      (0.47 +/- 0.07%; P < 0.02). CONCLUSIONS: Our data have demonstrated the presence
      of prolactin receptors in normal cadaveric pituitary and in most pituitary
      adenomas, irrespective of histological classification. In particular, elevated
      prolactin receptor levels were shown in PRL-secreting tumours from patients with
      markedly increased serum PRL levels. Our study may support several lines of
      experimental evidence for a specific functional role for PRL in the growth of
      some pituitary adenomas.

PMID- 7621569
TI  - Age related changes in the pituitary-testicular axis in normal men; lower serum
      testosterone results from decreased bioactive LH drive.
AB  - OBJECTIVE: The mechanism underlying the slight hypoandrogenism associated with
      normal ageing remains unclear. We have therefore examined age related changes in
      the activity of the pituitary-testicular axis in healthy normal males. DESIGN:
      Random blood samples were obtained from 219 normal men whose ages ranged from 20
      to 79 years. At the time of the study, none of the men had received treatment or
      had ever had any endocrine dysfunction diagnosed. MEASUREMENTS: Luteinizing
      hormone was measured in the subjects' plasma using a commercially available
      immunoradiometric assay (IRMA, Serono Maiaclone) and a fully validated in-vitro
      bioassay. Testosterone and FSH were measured using standard radioimmunoassays
      (RIA) whilst sex hormones binding globulin was assayed by an IRMA. RESULTS:
      Levels of total testosterone (total-T) and bioactive LH fell with age (r = -0.231
      and -0.189 respectively) by 5.9 nmol/l and 2.3 IU/l respectively between grouped
      patients aged 20-39 years (Group A) and 60-79 years (Group C). In contrast,
      immunoreactive LH remained unchanged. The LH B:I ratio also fell with age (P <
      0.0001) being 5.0 +/- 0.3 (group A) and 3.3 +/- 0.2 (group C), representing a
      fall of 33%. Since immunoreactivity remained constant, this fall primarily
      represented the decline in LH bioactivity. Bioactive, but not immunoreactive LH
      correlated to total-T (P = 0.009, n = 209) and the total-T:LH ratios fell by over
      30% between groups A and C using the IRMA, but remained unchanged by bioassay.
      CONCLUSIONS: There is an underlying decline in both total-testosterone and free
      testosterone index, and bioactive LH levels with advancing age, suggestive of a
      hypothalamo-pituitary defect which leads to lower bioactive LH levels which in
      turn are responsible for the diminished gonadal steroidogenesis. Elucidation of
      the mechanism underlying this slight decline in hypothalamopituitary testicular
      activity is complicated by differences between the data obtained by immunoassay
      or bioassay.

PMID- 7621570
TI  - The effect of a continuous infusion of a somatostatin analogue (octreotide) for
      two years on growth hormone secretion and height prediction in tall children.
AB  - OBJECTIVE: Strategies to limit the final height of tall children have centred on
      the use of high doses of sex steroids to advance skeletal maturation. This limits
      therapy to the peripubertal years whereas the greatest gain in height is in the
      prepubertal years. Prepubertal growth is largely GH dependent and previous work
      has documented modulation of GH secretion by once or twice daily subcutaneous
      injection of the somatostatin analogue octreotide. In this study we have
      determined the effects of a nocturnal infusion of octreotide on height
      prediction, GH and TSH secretion in tall children. DESIGN: A patient controlled
      study in which height prediction and 24-hour GH and TSH secretion were compared
      prior to and during the course of a 2-year treatment programme with a nocturnal
      infusion of octreotide in a dose of 1-1.5 micrograms/kg body weight given
      subcutaneously. PATIENTS: Nine tall children (4M; 5F) aged 7-14 years with final
      height predictions of 179 cm or greater in the girls and between 183 and 202 cm
      in the boys were studied. MEASUREMENTS: Height prediction using the Tanner
      Whitehouse system prior to and at the end of 2 years of treatment. Twenty-four
      hour serum GH and TSH concentration profiles, thyroxine, IGF-I and GH responses
      to GHRH(1-29)NH2 were studied prior to and at the end of the first year of
      therapy. RESULTS: Treatment with octreotide led to a significant reduction in
      height prediction in 7 of the 8 children who completed treatment (median
      reduction 3.5 cm, range +2.8 to -11.5; Wilcoxon, P = 0.05). Twenty-four-hour mean
      serum GH concentration decreased by 50% (MANOVA, P = 0.03) during therapy and
      this was accompanied by an increase in the percentage of samples giving values
      less than 0.5 mU/l (MANOVA, P = 0.02). There was no overall change in the serum
      GH response to GHRH(1-29)NH2 or serum IGF-I concentrations. Nocturnal serum TSH
      concentrations were reduced to levels observed during the daytime but these
      changes had no effect on serum thyroxine values. One patient developed gallstones
      during the course of therapy. CONCLUSIONS: A nocturnal infusion of octreotide
      reduces GH secretion and height prediction in tall children. Therapy with
      somatostatin analogues allows a reduction in growth rate to be instigated in the
      prepubertal years reducing the actual height from which will commence the
      pubertal growth spurt.

PMID- 7621571
TI  - Long-term effects of radioiodine on thyrotrophin receptor antibodies in Graves'
      disease.
AB  - OBJECTIVE: Graves' disease is recognized as an organ-specific autoimmune disorder
      caused by the presence of TSH receptor antibodies. The long-term effects of 131I
      treatment for Graves' disease on TSH receptor antibodies have not previously been
      studied. We have measured the TSH-binding inhibitory immunoglobulin (TBII) index
      and thyroid stimulating antibody (TSAb) activity in patients with Graves' disease
      following treatment with 131I. DESIGN: A retrospective study. PATIENTS: Two
      hundred and twenty-five patients with Graves' disease who were treated with 131I
      1-13 years earlier were studied (1 year: 27 patients; 2-5 years: 42 patients; 6-9
      years: 79 patients; 10-13 years: 77 patients). MEASUREMENTS: The TBII index was
      measured as the percentage 125I-TSH bound to pig thyroid membranes and TSAb
      activity as the amount of cAMP produced by cultured FRTL-5 cells. RESULTS: TBII
      was detected in 78% of patients prior to 131I administration. Following 131I
      administration, the incidence of positive TBII was 85% at the end of the first
      year decreasing to 40, 19, and 17% at 2-5, 6-9 and 10-13 years, respectively. The
      frequency of a positive TSAb was 74% at the end of the first year, and also
      decreased to 49, 27 and 29% at 2-5, 6-9 and 10-13 years, respectively. At more
      than 2 years after 131I therapy, the frequencies of hyperthyroidism in TBII and
      TSAb positive patients were 42% (19/45) and 30% (19/63), respectively, which were
      significantly higher than those in TBII and TSAb negative patients (8%: 12/153
      and 8%:11/131, respectively). The frequency of hyperthyroidism after 131I
      treatment in patients with negative TBII before treatment (7%:2/29) was
      significantly lower than that (29%:30/102) in patients with positive TBII before
      treatment. CONCLUSIONS: These results indicate that (1) the TBII index and TSAb
      activity decreased over a period of more than 2 years after 131I therapy for
      Graves' disease, and (2) the TBII index before treatment may influence the long
      term outcome of 131I therapy.

PMID- 7621572
TI  - Measurement of thyroglobulin in newborn screening specimens from normal and
      hypothyroid infants.
AB  - BACKGROUND AND OBJECTIVE: Thyroglobulin (Tg) has been found in varying
      concentrations in infants and children with congenital hypothyroidism. Our
      primary goal was to ascertain whether Tg in filter paper blood specimens used for
      routine newborn screening would be a useful adjunct in the early diagnosis of
      newborn children with congenital hypothyroidism. Our secondary objective was to
      correlate the results of the Tg determinations with the results of thyroid
      scintigraphy in the same cohort of infants with congenital hypothyroidism.
      DESIGN: An RIA kit with high sensitivity for the measurement of Tg in serum was
      modified for use with filter paper blood specimens. Results of thyroid
      scintigraphy were obtained from the family physicians on 10 infants with ectopic
      thyroid glands and 18 who were considered to be athyreotic. MEASUREMENTS:
      Determinations of Tg were carried out retrospectively on newborn screening filter
      paper blood specimens from 61 full-term normal infants and 42 newborns with
      confirmed congenital hypothyroidism. RESULTS: Thyroglobulin concentrations during
      the first week of life in the normal controls ranged between 17 and 160
      micrograms/l, with a median of 66 micrograms/l. Tg values for infants with
      ectopic thyroid glands ranged between 38 and 282 micrograms/l, with a median of
      160 micrograms/l, with a median of 66 micrograms/liters. Tg values for infants
      who were considered athyreotic had Tg values ranging between undetectable and 104
      micrograms/l with a median of 15 micrograms/l. Fifty per cent of the athyreotic
      patients and 50% of patients with ectopic thyroid glands had Tg values above or
      below the normal range and thus fell within the diagnostic category of
      hypothyroidism on the basis of Tg alone. Fifty per cent of patients who were
      considered athyreotic by scintigraphy had Tg concentrations ranging from 20 to
      104 micrograms/l. CONCLUSION: These studies have shown that thyroglobulin can be
      measured in the same filter paper blood specimens used for routine newborn
      screening. Estimation of thyroglobulin in screening specimens from hypothyroid
      and normal infants indicated that some infants with congenital hypothyroidism
      could be identified solely on the basis of the thyroglobulin concentration.
      Comparison of the result of scintigraphy with thyroglobulin levels in the same
      hypothyroid patients suggested that thryoglobulin provided a more reliable marker
      for the presence or absence of the thyroid gland than did scintigraphy.

PMID- 7621573
TI  - Lymphocytic hypophysitis: unusual features of a rare disorder.
AB  - OBJECTIVE: Lymphocytic hypophysitis is a rare disorder which usually affects
      women and is often associated with pregnancy. We reviewed our experience of this
      disorder in order to see whether these features were universal amongst our
      patients. DESIGN: A retrospective review of case notes. PATIENTS: Four patients
      with histologically proven lymphocytic hypophysitis. MEASUREMENTS: Each patient
      had undergone full radiological and biochemical assessment of anterior and
      posterior pituitary function. RESULTS: Only one woman presented during pregnancy,
      one patient was a man with coexistent active acromegaly, and one progressed over
      5 years to panhypopituitarism. In one further patient, histological analysis
      revealed normal anterior pituitary tissue adjacent to lymphocytic follicles.
      CONCLUSIONS: Lymphocytic hypophysitis should be considered in the differential
      diagnosis of any patient with a pituitary mass. We suggest that the entire
      removal of such a mass is warranted both for accurate diagnosis and definitive
      treatment.

PMID- 7621574
TI  - Hypercalcaemia.

PMID- 7621575
TI  - Mammosomatotroph adenoma causing gigantism in an 8-year old boy: a possible
      pathogenetic mechanism.
AB  - The pathophysiology of mammosomatotroph adenomas remains unclear. We studied a
      mammosomatotroph adenoma removed from an 8-year old boy with a 5-year history of
      growth acceleration and acromegalic gigantism at presentation. Elevated basal GH
      (mean 28 micrograms/l) and PRL (mean 120 micrograms/l) plasma levels were
      observed, as well as paradoxical responses of GH to L-dopa, TRH and oral glucose
      administration; PRL was reduced by L-dopa and slightly increased by TRH; GHRH
      stimulated release of both GH and PRL. Two operations were required to remove the
      very large tumour and the patient was treated with bromocriptine before the
      second. Hormonal secretion by tumour explants in culture was evaluated under
      basal conditions and after stimulation or inhibition. High levels of GH and PRL
      were secreted for up to 24 days. Furthermore, GHRH and TRH caused a dose-related
      stimulation of both hormones, while somatostatin and dopamine were effective in
      suppressing either basal or stimulated hormone release only at very high (microM)
      concentrations. Intracellular events were studied by determination of the
      guanosine triphosphate binding (G) protein levels and adenylate cyclase (AC)
      activity in the tumour tissue. Before bromocriptine treatment, AC activity was
      very high in the tumour and could be further stimulated by various agents; very
      high levels of the AC-stimulatory G protein alpha subunit Gs alpha and very low
      amounts of the AC-inhibiting G protein alpha subunit Gi3 alpha and of the
      phospholipase C-stimulating G protein alpha subunit Gq alpha were found in the
      tumour. After bromocriptine, baseline AC activity was normalized and could no
      longer be stimulated; Gs alpha and Gi3 alpha levels were unchanged while those of
      Gq alpha were normalized. Screening of tumour DNA after amplification by
      polymerase chain reaction followed by single-strand conformational polymorphism
      analysis did not reveal any mutations in the hot spots of G protein alpha
      subunits (alpha s, alpha i2, alpha o2 and alpha 11) genes or in the H-ras and p53
      genes. Gs alpha and GH transcription factor-1 (pit-1) expression were evaluated
      by amplification of cDNA. While the mRNA expression of pit-1 decreased after
      bromocriptine treatment, that of Gs alpha increased. These data suggest the
      possibility of an oncogenic process involving overexpression of Gs alpha,
      resulting in chronic activation of adenylate cyclase. Furthermore, our results
      suggest that the anti-secretory and anti-proliferative effects of bromocriptine
      may be mediated through a decrease in Pit-1 secondary to the inhibition of
      adenylate cyclase activity.

PMID- 7621576
TI  - Fetal osteocalcin levels are related to placental 11 beta-hydroxysteroid
      dehydrogenase activity in humans.
AB  - OBJECTIVE: Overexposure to glucocorticoids in utero reduces birth weight and, in
      animals, leads to persistent hypertension in the offspring. The fetus is normally
      protected from maternal glucocorticoids by placental 11 beta-hydroxysteroid
      dehydrogenase (11 beta-HSD) which catalyses the conversion of cortisol to inert
      cortisone. In adult humans, osteocalcin is a sensitive marker of glucocorticoid
      exposure. The aim of this study was to determine whether cord blood osteocalcin
      levels were related to the ability of placental 11 beta-HSD to inactivate
      maternal cortisol. DESIGN: Cross-sectional study examining the relation between
      cord blood levels of osteocalcin and placental glucocorticoid metabolism at term.
      PATIENTS: Twenty-one women attending for delivery at the Simpson Memorial
      Maternity Pavilion in Edinburgh had cord venous and arterial blood samples
      collected at delivery. MEASUREMENTS: Cord plasma levels of osteocalcin, cortisol
      and cortisone were measured by radioimmunoassay and indices of placental 11 beta
      HSD activity were calculated. RESULTS: All indices of placental 11 beta
      hydroxysteroid dehydrogenase activity correlated directly and significantly with
      cord blood osteocalcin levels. For cord blood osteocalcin and the placental 11
      beta-HSD Activity Index, Pearson's r was +0.58, r2 = 0.33 and P < 0.02.
      CONCLUSION: We conclude that term cord blood osteocalcin level reflects the
      effectiveness of placental glucocorticoid inactivation, and may be a marker for
      the development of adult hypertension.

PMID- 7621577
TI  - Identification of olfactory dysfunction in carriers of X-linked Kallmann's
      syndrome.

PMID- 7621578
TI  - Decreased cervicovaginal production of both IgA1 and IgA2 subclasses in women
      with AIDS.
AB  - Paired sera and cervicovaginal secretions from 35 HIV-1-infected women
      representing different CDC stages of HIV infection were evaluated for total IgA,
      IgA1 and IgA2, for IgA, IgA1 and IgA2 to gp160, and for albumin. Age-matched
      healthy women (n = 45) served as controls. The secretion rates of total IgA, IgA1
      and IgA2 were evaluated by calculating their relative coefficients of excretion
      by reference to albumin. In HIV-infected women, total IgA1 and IgA2 in sera and
      in cervicovaginal secretions increased proportionately as early as stages II +
      III and more markedly at stage IV. By contrast, the secretion rates of total IgA
      IgA1 and IgA2 were markedly reduced in AIDS women, the IgA2 secretion rate
      decreasing significantly as early as stages II + III. This apparent discrepancy
      was probably the result of increased transudation of serum-borne immunoglobulins
      into the vaginal cavity, since albumin levels in cervicovaginal secretions
      increased significantly according to the stages of disease. HIV-reactive IgA
      antibodies in serum, as in cervicovaginal secretions, were principally found
      within the IgA1 subclass. In women at stage IV, a high local production of IgA1
      to gp160 occurred in spite of the impairment of cervicovaginal IgA synthesis,
      probably because of marked genital HIV replication at advanced stages.

PMID- 7621580
TI  - Influence of the genetic pattern and sex of mice in experimental
      paracoccidioidomycosis.
AB  - Eight genetically different strains of mice were compared regarding the
      dissemination of Paracoccidioides brasiliensis to the lungs, liver and
      omentum/pancreas, DTH responses and specific antibody production at 16 weeks
      after intraperitoneal infection with Pb18, a virulent P. brasiliensis isolate.
      The degree of dissemination of the infection varied: B10.A and C57B1/6, the most
      susceptible mouse strains, had positive cultures and high colony-forming unit
      (CFU) counts in all analysed organs. DBA/2 and A/Sn mice had negative cultures,
      being thus classified as the most resistant strains. CBA/J, C3H/HeJ,
      F1(A/SnxB10.A) and BALB/c mice were regarded as relatively resistant, since
      discrete fungal growth was observed only in one or two of the studied organs. All
      mouse strains, except B10.A mice, produced specific DTH responses which did not
      seem to be associated with the severity of disease. Production of high levels of
      specific antibodies was found in all strains except in the DBA/2 and C57B1/6
      mice. The influence of the host sex on the outcome of paracoccidioidomycosis was
      evident only in susceptible animals: female B10.A mice displayed lower CFU counts
      in the three examined organs, whereas no differences were found between male and
      female A/Sn animals. The higher resistance of female B10.A mice was not
      accompanied by differences in their capacity to maintain a DTH reaction, nor in
      their production of antibody. This fact argues against the widely believed
      association of susceptibility to P. brasiliensis infection with both impaired DTH
      reactivity and increased humoral response.

PMID- 7621581
TI  - Enhanced expression of MHC class I molecules on cultured human thyroid follicular
      cells infected with reovirus through induction of type 1 interferons.
AB  - Certain viruses are known to modulate the cellular expression of MHC molecules.
      We have investigated whether reovirus types 1 or 3 can alter the normal MHC
      molecule expression on cultured human thyroid follicular cells (TFC). Primary TFC
      cultures were established from eight human thyroid donors and MHC class I and II
      expression was assessed by indirect immunofluorescence microscopy. Both types of
      reovirus enhanced MHC class I expression on TFC from all thyroid donors. Class II
      MHC protein was strongly induced by type 1 reovirus on TFC from one donor, while
      weak induction of expression, by either reo-1 or reo-3 virus, was noted on the
      TFC of five other donors. Studies on the mechanism(s) of MHC class I
      hyperexpression showed that mouse MoAb against the type 3 reovirus haemagglutinin
      (anti-HA3) reduced the ability of the virus to induce hyperexpression of class I
      MHC molecules on TFC. However, supernatant harvested from type 3 reovirus
      infected TFC cultures maintained its ability to enhance class I expression after
      incubation with anti-HA3. Moreover, adding rabbit anti-sera to interferon-alpha
      (IFN-alpha) or IFN-beta inhibited the increased class I MHC expression on TFC by
      both types of reovirus. These data suggest that reoviruses (types 1 and 3) can
      enhance MHC class I on cultured TFC. The mechanism of MHC class I enhancement is
      most probably through the release of IFN-alpha and IFN-beta.

PMID- 7621579
TI  - Identification of HIV protein-derived cytotoxic T lymphocyte (CTL) epitopes for
      their possible use as synthetic vaccine.
AB  - CTL are by far the most important defence mechanisms against viral infections,
      and many attempts have been undertaken to induce protective CTL in vivo. In order
      to identify CTL epitopes for their possible use as peptide-vaccine candidates,
      HIV proteins were screened for peptide sequences which (i) fulfil the binding
      motif of the HLA-A2.1 molecule, and (ii) are involved in the natural immune
      response to HIV. From 73 nonameric peptides satisfying the binding motif, 20
      peptides were synthesized and their binding to HLA-A2.1 was monitored by
      measuring the expression of HLA-A2.1 molecules on the cell surface of the mutant
      cell line T2. To evaluate the involvement in natural HIV infection, strongly
      binding peptides were used in cytotoxicity assays to assess their capacity to
      generate a peptide-specific CTL response in vitro. From 20 nonameric peptides
      synthesized, only five showed strong binding to HLA-A2.1. All five binding
      peptides had the secondary anchor residues, recently proposed by Ruppert et al.
      [1] to be required for binding to HLA-A2.1. The discrimination between bound and
      unbound peptides confirmed the importance of these secondary anchor residues
      which, beside the known binding motif, may dictate if a peptide can bind to HLA
      A2.1 or not. In HIV- donors, no CTL activity against any of the HIV-derived
      peptides was detectable after a 12-day in vitro stimulation. In contrast, HIV
      infected persons showed a cytotoxic response against peptide-labelled target
      cells, suggesting that they had developed upon HIV infection a cytotoxic immune
      response against the identified CTL epitopes.

PMID- 7621582
TI  - Brain-reactive autoantibodies in BB/d rats do not recognize glutamic acid
      decarboxylase.
AB  - The BB rat spontaneously develops insulin-dependent diabetes mellitus (IDDM)
      similar to that in humans. The most practical markers of beta cell autoimmunity
      are circulating antibodies to islet cell components. In particular autoantibodies
      to the enzyme glutamic acid decarboxylase (GAD) are a common feature of IDDM
      development in humans. This study aims at investigating the prevalence and levels
      of autoantibodies in BB rats to antigens in a semipurified, GAD-enriched
      preparation from rat brain. Eighteen diabetes-prone BB/d rats (10 male and eight
      female) were tail bled weekly from age 28 days to 113 days and antibodies
      detected on the rat brain preparation by ELISA. Antibody levels were expressed as
      arbitrary units relative to a standard positive serum. Individual rats varied in
      the time and order of antibody appearance and IDDM onset, with the earliest
      occurrence being 42 days and 69 days, respectively. In some rats antibody
      production was maintained but declined in others. By 113 days 85% of diabetic
      rats had at some time been positive for autoantibodies to brain components,
      compared with 25% of non-diabetics (P = 0.09 by Fisher's exact test).
      Immunoabsorption studies using recombinant rat GAD-65 or recombinant human GAD-67
      failed to inhibit the binding of BB rat sera to the original rat brain
      preparation. A capture ELISA using GAD-6 MoAb to capture GAD-65 from rat brain
      preparation or from a preparation of recombinant rat GAD-65, failed to detect
      anti-GAD antibodies in BB rats. Immunofluorescent staining of tissue sections
      showed the autoantibodies to be brain-specific, but having distinct staining
      patterns to the anti-GAD antibodies of Stiff Man Syndrome serum. In conclusion,
      BB rats possess autoantibodies reactive with rat brain antigens which may be
      associated with IDDM. However, these are not directed against GAD.

PMID- 7621583
TI  - Activation of the endothelium by IL-1 alpha and glucocorticoids results in major
      increase of complement C3 and factor B production and generation of C3a.
AB  - Constitutive secretion of complement C3 and factor B by the endothelial cell (EC)
      is lowered by therapeutic concentrations of glucocorticoids such as
      hydrocortisone or dexamethasone, whereas regulatory protein factor H production
      is increased by these hormones. In contrast, the proinflammatory cytokine IL-1
      alpha has a stimulatory effect on C3 and factor B secretion by the endothelium
      and an inhibitory effect on factor H secretion. In this study, we examined the
      combined effect of IL-1 alpha and glucocorticoids on C3 and factor B expression
      by the endothelial cell. When dexamethasone or hydrocortisone were added to IL-1
      alpha, significant potentialization of IL-1 alpha-induced stimulation of C3 and
      factor B production was observed, occurring at various concentrations of either
      stimuli. Dose-response experiments indicate that, in vitro, optimal
      concentrations are in the range of 10(-7) to 10(-5) M for dexamethasone and 50
      200 U for IL-1 alpha. In contrast, dexamethasone counteracts, in an additive way,
      the inhibitory effect of IL-1 alpha on regulatory complement protein factor H
      production by EC. Such a potentialization between glucocorticoids and IL-1 alpha
      was not observed for another marker of endothelial activation, IL-1 alpha-induced
      stimulation of coagulation tissue factor expression. The association of
      glucocorticoids and IL-1 alpha therefore appears to be a specific and major
      stimulus for the secretion of complement C3 and factor B, two acute-phase
      proteins, by the endothelium. As a result of the in vitro endothelium stimulation
      by glucocorticoids and IL-1 alpha, C3a is generated in the vicinity of the
      endothelial cell. This study further suggests that complement activation, with
      its deleterious consequences, may result from the stimulation of endothelium in
      situations where high levels of IL-1 alpha and endogenous glucocorticoids
      coexist, such as in septic shock.

PMID- 7621584
TI  - IL-13 results in differential regulation of the complement proteins C3 and factor
      B in tumour necrosis factor (TNF)-stimulated fibroblasts.
AB  - IL-13, like IL-4, a product of activated T cells, has multiple biological
      actions, primarily on B cells and monocytes. The purpose of the present study was
      to compare the effects of IL-13 with those of IL-4 on the synthesis of complement
      proteins in fibroblasts. Dermal fibroblasts were developed from skin biopsies.
      Confluent monolayers were stimulated with the relevant cytokine or combinations
      of cytokines and biosynthetically labelled with 35S-methionine. The specific
      proteins were analysed using immunoprecipitation and SDS-PAGE. Addition of IL-13
      to fibroblast cultures treated with TNF-alpha resulted in a dose-dependent
      increase in C3 protein biosynthesis and a concomitant down-regulation of factor B
      protein biosynthesis. In TNF-stimulated fibroblasts, the addition of IL-13, 100
      ng/ml, induced a 2.45-fold increase in the synthesis of C3, while in the same
      cells under identical conditions the synthesis of factor B was only 42% of the
      level without IL-13. Similar effects of IL-13 were noted on IL-1-treated
      fibroblasts. These effects were specific for C3 and factor B, and no alteration
      of the constitutive or TNF-induced synthesis of C1s or C1 inhibitor proteins was
      observed. IL-13 altered the synthesis of C3 and factor B proteins also in
      fibroblasts stimulated with interferon-gamma (IFN-gamma) in addition to TNF, in
      the same direction as it did in cells stimulated with TNF alone. IL-13 has
      similar effects to those of IL-4 on the synthesis of C and factor B in TNF- and
      IL-1-stimulated fibroblasts. The observed effects of IL-13 are IL-4-independent,
      as anti-IL-4 antibody abrogates IL-4-induced effects, but has no effect on IL-13
      induced responses. This interaction between different cytokines on the synthesis
      of proinflammatory and immunoregulatory proteins may have significance,
      particularly at local sites of inflammation, and may affect the synthesis of
      complement proteins in inflamed joint as in rheumatoid arthritis.

PMID- 7621585
TI  - Antigen-presenting function of human peritoneum mesothelial cells.
AB  - Mesothelial cells (MC) from human peritoneal omentum fragments obtained during
      surgical insertion of peritoneal catheters for continuous peritoneal dialysis in
      end stage renal failure (ESRF) patients were cultured in vitro. MC exhibited a
      phenotype different from macrophages, but MHC class II molecules were well
      expressed. Therefore MC lines were tested for antigen-presenting capacity by
      pulsing with soluble antigens (tetanus toxoid and purified protein derivative
      (PPD)) or with a corpusculate antigen (Candida albicans bodies). Autologous
      peripheral blood mononuclear cells (PBMC) depleted of adherent monocytes and
      cloned T cells generated from an individual matched for the MHC class II antigen
      DR2 were used to test antigen-presenting function. MC effectively presented the
      soluble and corpusculate antigens to autologous and MHC-compatible allogeneic
      lymphocytes, indicating that they are endowed with both endocytic/phagocytic
      activity and with processing/presenting capacity. Preincubation of MC with human
      recombinant interferon-gamma (IFN-gamma) up-regulated MHC class II and
      intercellular adhesion molecule-1 (ICAM-1) expression, but the effect on antigen
      presenting function was not consistent. Since MC are an important component of
      the peritoneal environment, they may participate, along with macrophages, in
      activation of specific T cells and in the generation of local cell-mediated
      immunity to various pathogens.

PMID- 7621587
TI  - Large granular lymphocyte expansions in patients with Felty's syndrome: analysis
      using anti-T cell receptor V beta-specific monoclonal antibodies.
AB  - Felty's syndrome (FS), the association of rheumatoid arthritis (RA) and
      idiopathic neutropenia, remains an unexplained phenomenon. HLA-DR4 is found in
      over 90% of cases. Patients with FS may have a T cell lymphocytosis of
      CD3+CD8+CD57+ large granular lymphocytes (LGL syndrome). In this study of 47
      patients with FS, 19% had clear evidence for LGL expansions, while in total 42%
      had variable evidence for the LGL syndrome using currently available techniques.
      Of these T cell expansions, 76% were clonal, as demonstrated by Southern blotting
      and analysis with T cell receptor (TCR) beta chain constant region probes. This
      technique may fail to detect clonal populations in some patients.
      Cytofluorographic analysis using antibodies specific for TCR V beta chains
      identified patients with clonal LGL expansions with results comparable to those
      obtained with Southern blotting. No evidence for shared V beta usage among
      expansions from different patients was seen. The role of LGL in RA and FS is
      currently unclear, but this technique offers a practical and accessible means of
      identifying patients with LGL expansions, as a starting point for further
      investigation.

PMID- 7621586
TI  - Modulation of the IL-1 cytokine network in keratinocytes by intracellular IL-1
      alpha and IL-1 receptor antagonist.
AB  - The IL-1 cytokine network in epidermal cells was studied in vitro, using the
      spontaneously transformed HaCAT human keratinocyte line. Intracellular (ic) IL-1
      alpha and IL-1 receptor antagonist protein (IL-1Ra) following cell lysis were
      readily identified assayed using a capture ELISA; whereas in culture supernatants
      IL-1Ra was not detected, and IL-1 alpha was present at only very low levels.
      Confluent cultures of HaCAT cells were shown to provide optimal conditions for
      the study, since confluence increased the icIL-1Ra:IL-1 alpha ratio to a level as
      seen in vivo, which was independent of Ca2+ concentration in the culture medium.
      The IL-1Ra extracted from HaCAT cell lysates was functionally active, as
      demonstrated in the mouse thymocyte co-proliferation assay which could be blocked
      using a rabbit anti-IL-1Ra antibody. Transforming growth factor-beta (TGF-beta 1)
      stimulated a dose-dependent increase in HaCAT cell IL-1 alpha without changing IL
      1Ra concentration, with a resultant reduction in the icIL-1Ra: IL-1 alpha ratio
      from 320:1 to 100:1. Similarly, TGF-alpha, interferon-gamma (IFN-gamma), IL-6,
      and tumour necrosis factor-alpha (TNF-alpha) substantially increased HaCAT cell
      IL-1 alpha, but had no effect on the IL-1Ra, with a concomitant reduction in the
      icIL-1Ra:IL-1 alpha ratio. In contrast to their effects on monocytes, IL-4 and IL
      10 at biologically active levels had no effect on IL-1 alpha, IL-1Ra or the icIL
      1Ra: IL-1 alpha ratio in confluent HaCAT cells. Hydrocortisone reduced IL-1 alpha
      to below the limit of sensitivity of the ELISA, and induced a small increase in
      IL-1Ra of questionable biological significance. Thus, regulation of the IL-1
      cytokine network in keratinocytes involves modulation of icIL-1 alpha rather than
      of icIL-1Ra levels, and is markedly different from that noted in monocytes.

PMID- 7621589
TI  - Neutrophil expression of tumour necrosis factor receptors (TNF-R) and of
      activation markers (CD11b, CD43, CD63) in rheumatoid arthritis.
AB  - In vitro analysis of polymorphonuclear neutrophils (PMN) has allowed various
      stages of cell activation to be distinguished, characterized by the expression
      level of specific membrane markers and of functional receptors. Among those, TNF
      alpha receptors (TNF-R) are modulated by various PMN activators, a mechanism
      which may be important to control cell responses to TNF in inflammatory reactions
      such as rheumatoid arthritis (RA). PMN, isolated from the blood of 36 RA patients
      and from the synovial fluid of 23 of them, were analysed for membrane expression
      of the two TNF-R (p55 and p75). Soluble p55 and p75 (sTNF-R) and TNF
      concentrations were measured in the plasma and synovial fluid by specific ELISA
      assays. Our results show that PMN from the blood of RA patients bear a normal
      number of TNF-R, with a normal p55/p75 ratio, compared with PMN from normal
      controls. Soluble TNF-R levels were similar in patients and normal plasma. In
      spite of high endogenous TNF concentration, patients' circulating PMN were not
      activated, as shown by a CD11b/CD18 expression similar to that of control resting
      cells. In contrast with blood neutrophils, PMN from RA patients' synovial fluids
      had an activated phenotype, characterized by increased expression of CD11b,
      decreased expression of leukosialin, CD43, and the appearance on the plasma
      membrane of an azurophil granule protein, CD63. High levels of soluble TNF-R were
      measured in RA synovial fluids. Nevertheless, membrane TNF-R levels and p55 and
      p75 proportions were similar to those of PMN from normal blood. These results
      suggest the existence of regulatory mechanisms which maintain a stable neutrophil
      expression of TNF-R as well as a balance between both types of receptors in
      inflammatory situations where neutrophils are strongly activated.

PMID- 7621590
TI  - Diverse T cell receptor beta gene usage by infiltrating T cells in the lacrimal
      glands of Sjogren's syndrome.
AB  - Sjogren's syndrome (SS) is an autoimmune disease characterized by T cell
      infiltration into the salivary and lacrimal glands (LG). Previous studies on T
      cell receptor (TCR) usage in the minor salivary glands (SG) have yielded
      controversial results. We studied TCR beta gene usage of the T cells infiltrating
      to LG, which is the other major target organ of SS. Total RNA was extracted from
      fresh LG and SG biopsy samples, and peripheral blood mononuclear cells from five
      SS patients, and converted to cDNA. TCR V beta gene repertoire was then assessed
      with quantitative polymerase chain reaction (PCR) assay. Oligoclonality was
      studied by sequencing V-D-J junctional regions of the PCR products. The TCR V
      beta gene usage in LG was diverse in every patient irrespective of disease
      duration, and similar to that of peripheral lymphocytes from a corresponding
      patient. The junctional region sequences of over-expressed V beta families in LG
      T cells were heterogeneous. We did not find any identical clones shared by LG, SG
      and peripheral blood. These results showed that the infiltrating T cells in LG of
      SS patients are polyclonal, and LG and SG do not share the same dominant T cell
      clonotypes. These suggest that TCR-targeted disease manipulation may have a
      limited effect on SS.

PMID- 7621588
TI  - Treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated systemic
      vasculitis with high-dose intravenous immunoglobulin.
AB  - In this uncontrolled study 15 patients with ANCA-associated systemic vasculitis,
      who were poor responders to conventional therapy, were treated with single or
      multiple courses of intravenous immunoglobulin (IVIG), 30 g/day over 5 days.
      Clinical and serological evaluation was performed before and 4 weeks after IVIG.
      Six of the 15 patients experienced clinically significant benefit from IVIG.
      Improvement was confined to single organ manifestations (skin, ENT findings), no
      improvement was seen with conjunctivitis and scleritis, pericarditis or
      nephritis. No patient experienced complete remission after IVIG. Repeated courses
      of IVIG at 4-week intervals were no more effective than single courses. In six
      anti-proteinase 3 (PR3)-positive patients pretreatment sera were incubated with
      F(ab')2 fragments of the IVIG preparation in vitro to measure the inhibitory
      effect of IVIG on anti-PR3 activity. An inhibition of anti-PR3 activity by 25-70%
      was observed; this did not correlate with clinical effects. Approximately 40% of
      patients benefited from IVIG treatment, though complete remission of disease
      activity did not occur. Neither clinical characteristics nor the inhibitory
      effect of the IVIG preparation on serum anti-PR3 activity in vitro predicted
      clinical response to this treatment modality.

PMID- 7621591
TI  - Characterization of murine monoclonal antibodies against 60-kD Ro/SS-A and La/SS
      B autoantigens.
AB  - Small cytoplasmic ribonucleoproteins (scRNPs) are important autoantigens in
      patients with systemic lupus erythematosus and Sjogren's syndrome. MoAbs against
      these proteins were made by immunization of BALB/c mice with purified human
      recombinant 60-kD Ro/SS-A or 50-kD La/SS-B proteins. Five stable hybridoma cell
      lines were obtained, of which four secreted anti-Ro/SS-A antibodies (clones 1D8,
      1D11, 2G10 and 6G8) and one produced anti-La/SS-B antibodies (clone 7F6). The
      MoAbs were further characterized using four different immunoassays:
      immunofluorescence, immunoblotting, RNA precipitation combined with Northern
      blotting, and recombinant protein precipitation. All four MoAbs against Ro/SS-A
      recognized the native protein and one of them (2G10) recognized also intact scRNP
      particles. Interestingly, hY3-RNA was reproducibly not efficiently precipitated
      by MoAb 2G10. Epitope mapping using deletion mutants of the 60-kD Ro/SS-A antigen
      showed that MoAb 1D8 recognized the C-terminal part of this protein, while 1D11
      and 2G10 recognized distinct epitopes in the region between the RNP motif and the
      putative zinc finger domain. The epitopes recognized by these MoAbs are highly
      conserved among species, and the epitope recognized by MoAb 2G10 may be identical
      to an autoepitope recognized by sera of patients. This is the first report
      describing the isolation and characterization of MoAbs of the IgG class against
      the 60-kD Ro/SS-A and La/SS-B autoantigens obtained by immunization with purified
      human recombinant proteins. These MoAbs can be of great use in studying the
      cellular processes in which scRNPs are involved, and may help to determine why
      these scRNPs become autoantigenic in autoimmune diseases.

PMID- 7621592
TI  - No evidence for an independent role of anti-heparan sulphate reactivity apart
      from anti-DNA in lupus nephritis.
AB  - The presence of anti-heparan sulphate (HS) reactivity in serum is closely related
      to the occurrence of nephritis in patients with systemic lupus erythematosus
      (SLE). Since patients with lupus nephritis in general also have high titres of
      anti-DNA antibodies, we wanted to clarify the relationship between anti-HS and
      anti-DNA reactivity in serum. Therefore, we studied longitudinally six patients
      with lupus nephritis who experienced 12 exacerbations of their disease, and five
      SLE patients without nephritis experiencing 10 periods of non-renal disease
      exacerbations. In addition, we tested single serum samples of another 24 patients
      obtained during a renal disease exacerbation and 22 sera of patients without
      nephritis. The sera of all patients were tested for anti-DNA (Farr assay) and
      anti-HS reactivity (ELISA). We confirmed that SLE patients during renal
      exacerbations have a significantly higher anti-HS reactivity than patients
      without nephritis (P < 0.003). In addition, patients with nephritis also had
      higher titres of anti-DNA antibodies during renal exacerbations than during non
      renal exacerbations (P < 0.01). A correlation between anti-DNA and anti-HS
      reactivity was observed (r = 0.40, P < 0.02), which in itself explains the
      correlation between nephritis and anti-HS reactivity. Comparing sera from
      nephritis and non-nephritis patients matched for anti-DNA titre, we found no
      difference in anti-HS reactivity, and therefore must conclude that the anti-HS
      reactivity is a direct reflection of anti-DNA reactivity.

PMID- 7621594
TI  - Methotrexate treatment in murine experimental systemic lupus erythematosus (SLE);
      clinical benefits associated with cytokine manipulation.
AB  - The objective of this study was to determine the effects of Methotrexate (MTX) on
      the development and the course of experimental murine SLE, as well as on the
      cytokine profile involved in the disease. SLE was induced in naive BALB/c female
      mice by injection of the human anti-DNA MoAb bearing a common idiotype (16/6 Id).
      Six weeks following immunization, when high levels of autoantibodies were
      demonstrated, the mice were treated with MTX (2 mg/kg once a week) for a period
      of 10 months. MTX treatment had no effect on 16/6 Id-induced autoantibody
      production. However, MTX treatment had beneficial effects on the clinical
      manifestations of the experimental disease (i.e. leucocyte counts, levels of
      protein in the urine and immune complex deposits in the kidneys). Thus, only 20%
      of 16/6 Id-immunized BALB/c mice that were treated with MTX had immune complex
      deposits in their kidneys compared with 100% of SLE-afflicted BALB/c mice that
      were not treated. We have observed a significant elevation in IL-1, tumour
      necrosis factor (TNF) and IL-10 secretion in BALB/c mice afflicted with
      experimental SLE. IL-2, IL-4, IL-6 and interferon-gamma (INF-gamma) levels were
      decreased in these mice compared with the levels detected in healthy controls.
      Treatment with MTX reversed the levels of all the above cytokines to normal
      levels observed in control mice. These studies demonstrate therapeutic effects of
      MTX on murine experimental SLE. The normal cytokine profile observed following
      treatment with MTX is suggested to play a role in the amelioration of the
      clinical manifestations of experimental SLE.

PMID- 7621596
TI  - Early onset of autoimmunity in MRL/++ mice following immunization with beta 2
      glycoprotein I.
AB  - Antiphospholipid antibodies (aPL) are associated with thrombosis,
      thrombocytopenia and recurrent fetal loss in humans and in some animal models.
      Immunization with beta 2 glycoprotein I (beta 2GPI) induced aPL production in
      normal rabbits and mice. However, the association of these antibodies with
      disease manifestations remains controversial. To determine whether induction of
      aPL by beta 2GPI immunization in an autoimmune strain of mice (MRL/++) would
      result in acceleration of clinical and serological autoimmune disease
      manifestations, three groups of 8-week-old female mice were studied. One group
      was immunized with beta 2GPI, and one with ovalbumin (OVA); the third was not
      immunized. After two booster injections, sera were analysed for the presence of
      anticardiolipin (aCL) and anti-DNA by ELISA and anti-nuclear antibody (ANA) by
      immunofluorescence. Mice were studied for thrombocytopenia, proteinuria,
      fecundity rates, litter sizes and the development of central nervous system
      dysfunction. Elevated levels of aCL, anti-DNA and ANA were detected in all beta
      2GPI-immunized, in three OVA-immunized, and in none of the unimmunized mice. The
      anti-DNA antibodies were inhibited by CL micelles, suggesting cross-reactivity
      between aCL and anti-DNA. Platelet counts, fecundity rates and litter size were
      reduced in beta 2GPI-immunized but not in OVA-immunized or unimmunized mice. None
      of the mice developed neurological dysfunction or significant proteinuria over a
      10-week period post-immunization. These findings suggest that beta 2GPI
      immunization induces aPL in MRL/++ mice associated with accelerated autoimmune
      manifestations resembling the antiphospholipid syndrome.

PMID- 7621595
TI  - CDR3 regions in the preimmune VH B cell repertoire of lpr mice.
AB  - Previous studies have suggested that the CDR3 genetic element of the heavy chain
      variable region of autoantibodies is important in determining reactivity against
      self antigens, particularly against DNA. The lpr mutation was recently found to
      encode for a defective form of the fas protein, a molecule important for the
      transmission of the apoptotic signal into cells. Our aim was to determine whether
      CDR3 elements similar to those described for autoantibody-producing hybridomas
      derived from lupus-prone strains could be found in the preimmune repertoire of B
      cells in mice with the lpr mutation. The analysis of the junctions of the VH-C mu
      functional rearrangements derived by polymerase chain reaction (PCR)
      amplification of RNA obtained from splenic small, resting cells stimulated with
      lipopolysaccharide (LPS) from male lpr mice showed that a large proportion of
      them expressed D genes in the unusual reading frames 2 and 3. Two of the lpr
      joints were formed by D-D fusions. Similarly, nearly half of the lpr sequences
      had arginines, an amino acid which promotes binding to dsDNA and is seldom
      observed in normal junctions. Our results show that the preimmune repertoire of
      lpr animals has abnormal CDR3 elements which may result from a failure at
      different levels of selection. The antigen-dependent selection of such elements
      that leads to the expansion of specific, high-affinity anti-dsDNA antibody
      producing clones might depend on other genetic factors not found in the C57B1/6
      lpr strains but in the MRL-lpr.

PMID- 7621597
TI  - Proteolysis of classic anti-neutrophil cytoplasmic autoantibodies (C-ANCA) by
      neutrophil proteinase 3.
AB  - C-ANCA, which are directed against neutrophil proteinase 3 (PR3), are specific
      markers for the diagnosis of active Wegener's granulomatosis (WG). The
      correlation between C-ANCA titre and WG disease activity suggests that these
      autoantibodies are involved in the development of WG. We have previously observed
      that C-ANCA interfere with PR3 proteolytic activity and with complexation of PR3
      with its major physiologic inhibitor alpha 1-antitrypsin (alpha 1-AT). The
      possible pathogenic importance of C-ANCA may be related to the stability of C
      ANCA IgG-PR3 complexes. In the present study we tested proteolysis by PR3 of
      human IgG and proteolysis of C-ANCA IgG complexed to the enzyme. All human IgG
      subclass proteins were cleaved by PR3. Digestion products were compared with
      those obtained by human neutrophil elastase (HNE)-mediated proteolysis of human
      IgG subclass proteins. Although cleavage products of similar size could be
      identified, the proteolytic activity of both enzymes towards human IgG differed.
      Furthermore, inhibiting C-ANCA IgG were cleaved into small peptides when
      complexed to PR3. The possible pathogenic consequences of these findings will be
      discussed.

PMID- 7621598
TI  - Defects in antigen-driven lymphocyte responses in common variable
      immunodeficiency (CVID) are due to a reduction in the number of antigen-specific
      CD4+ T cells.
AB  - T cells from patients with CVID have defects that may relate to the failure in
      vivo of B cell production of antibodies. Antigen-driven responses of T cells from
      CVID patients and normal subjects have been assessed by measuring DNA synthesis
      in vitro. Low density cells enriched for antigen-presenting dendritic cells were
      pulsed with purified protein derivative (PPD) and cultured with autologous T
      cells. Overall, T cells from CVID patients showed a significantly low mean
      response to PPD, although non-specific DNA synthesis induced in CVID T cells by
      IL-2 was within the normal range. However, mean PPD-specific T cell responses in
      CVID were not restored by IL-2 irrespective of the presence of monocytes.
      Depletion of CD8+ cells also failed to restore the mean PPD response of CVID CD4+
      T cells. Limiting dilution analysis showed that in CVID there was a reduced
      frequency of antigen-specific cells within the T cell preparations. The mean
      frequency of the PPD-specific T cells in cultures from patients vaccinated with
      bacille Calmette-Guerin (BCG) was reduced to 1 in 109,000 T cells compared with 1
      in 18,600 T cells in BCG-vaccinated normal donors. These data show that the
      reduced PPD-specific response in CVID is due to a partial peripheral loss of
      antigen-specific cells.

PMID- 7621599
TI  - Tetanus toxoid-specific T cell responses in severe combined immunodeficiency
      (SCID) mice reconstituted with human peripheral blood lymphocytes.
AB  - SCID mice reconstituted with human peripheral blood lymphocytes (PBL) have
      repeatedly been shown to produce antigen-specific B cell responses. We have
      derived tetanus toxoid (TT)-specific human T cell lines from cells of the
      peritoneal cavity, spleen and lymph nodes of SCID mice reconstituted with human
      PBL and boosted with TT. Establishment of these cell lines was dependent on the
      time interval between reconstitution of the mice with human PBL and initiation of
      lymphocyte cultures in vitro. When lymphocytes were collected from the mice 8
      weeks after reconstitution, human lymphocytes with TT-specific proliferative
      activity in vitro were isolated from the peritoneal cavity and spleen, but long
      term cell lines could not be established after repeated lymphocyte stimulation
      with TT, IL-2 and autologous Epstein-Barr virus-transformed B cells. In contrast,
      three long-term (> 10 months) TT-specific human T cell lines were established
      from lymphocytes collected from two of the eight mice in the group 4 weeks after
      reconstitution. The T cell lines were either CD4+ (two lines derived from
      peritoneal cavity and lymph node, respectively) or CD8+ (one line derived from
      spleen) and all expressed CD3, T cell receptor alpha/beta, and human
      histocompatibility leucocyte class I antigen. The T cell lines, however, lacked
      cytotoxic, helper and suppressor activities. Thus, SCID mice can support human T
      cells that actively migrate to various organs and respond to antigenic stimuli
      both in vivo and in vitro, but these T cells lack characteristic functions.

PMID- 7621601
TI  - Physiological functions of atrial natriuretic factor prohormone peptides:
      introduction.

PMID- 7621593
TI  - Complement receptor expression and activation of the complement cascade on B
      lymphocytes from patients with systemic lupus erythematosus (SLE).
AB  - It has previously been reported that the expression of the complement receptors,
      CR1 on erythrocytes and blood leucocytes and CR2 on B cells, is reduced in
      patients with SLE, and that the reduced expression of CR1 on erythrocytes is
      related to disease activity. We have earlier demonstrated that normal B cells are
      capable of activating the alternative pathway (AP) of complement in a CR2
      dependent fashion. In this study we have investigated whether disturbances in
      this activity may be related to the altered phenotype of SLE B cells. Flow
      cytometry was used to measure expression of complement receptors and regulatory
      proteins on B cells from SLE patients, as well as the deposition of C3 fragments
      occurring in vivo or after in vitro AP activation. We have confirmed, for a
      proportion of the patients studied, reduced expression of CR1 and CR2 on B cells,
      and shown a consistency between low CR2 expression and reduced in vitro AP
      activation in the presence of homologous, normal serum. In addition, the B cells,
      like erythrocytes, bear raised levels of in vivo-deposited C3dg, but not C3b
      fragments, compared with normal B cells. The erythrocytes from SLE patients were
      unable to inhibit in vitro AP activation by B cells in homologous serum. Finally,
      we demonstrated an inverse relationship between SLE disease activity index
      (SLEDAI) and the expression of complement receptor 2 (CR2) on SLE B cells. Thus,
      determination of CR2 on B cells may emerge as an additional laboratory tool in
      the assessment of SLE activity.

PMID- 7621600
TI  - Neutrophil platelet-activating factor production and acetyltransferase activity
      in clinical acute myocardial infarction.
AB  - 1. Neutrophil function was studied in 10 males presenting with acute myocardial
      infarction (MI) within 6 h of onset and in 10 normal males. Neutrophil production
      of platelet-activating factor (PAF), determined by bioassay, that of leukotriene
      B4 by HPLC, and the activity of an enzyme involved in the synthesis of PAF,
      acetyltransferase (AT), were measured before and after stimulation with opsonized
      zymosan and calcium ionophore, A23187. 2. The neutrophil count was significantly
      raised at presentation in those with MI (8.2 +/- 0.8 vs 2.8 +/- 0.3 (s.e.m.) x
      10(9) cells/L, P < 0.001; t-test, 18 d.f.). Production of PAF per neutrophil in
      response to both stimulants was greater than normal in those with MI (zymosan: 21
      +/- 4 vs 12 +/- 1 ng/10(7) cells, P < 0.05; ionophore: 174 +/- 18 vs 113 +/- 11
      ng/10(7) cells, P < 0.02) despite normal leukotriene B4 production and depressed
      AT activity. By 7 days, the neutrophil count had significantly fallen but it
      remained greater than normal as did PAF production. 3. Acute MI is associated
      with increased potential for production of PAF by neutrophils which may be
      important in the pathogenesis of MI.

PMID- 7621602
TI  - Atrial natriuretic hormones originating from the N-terminus of the atrial
      natriuretic factor prohormone.
AB  - 1. Four peptide hormones consisting of amino acids 1-30 (Long Acting Sodium
      Stimulator), 31-67 (Vessel Dilator), 79-98 (Kaliuretic Stimulator) and 99-126
      (atrial Natriuretic Factor [ANF]) originate from the same 126 amino acid ANF
      prohormone. 2. Each of these four peptide hormones circulates as a distinct
      peptide with vessel dilator and long acting sodium stimulator circulating at 10-
      to 24-fold higher concentrations than ANF while kaliuretic stimulator circulates
      at a three-fold higher concentration than ANF. 3. Each of these peptide hormones
      is released with an increase in central volume causing stretch of the atrium of
      the heart and with rapid heart beats greater than 125 beats/min. 4. Each of these
      peptide hormones lowers blood pressure, causes a diuresis and enhances sodium
      and/or potassium excretion. 5. In disease states which retain sodium and water
      such as congestive heart failure (CHF), each of these atrial peptides increases
      in the circulation proportionately to the severity of sodium retention, but of
      the radioimmunoassays to each of these hormones only the vessel dilator
      radioimmunoassay differentiates between mild (class I) CHF and healthy
      individuals.

PMID- 7621604
TI  - Regulation of collecting duct Na+ reabsorption by ANP 31-67.
AB  - 1. The bulk of studies of the actions of atrial natriuretic peptides (ANP) have
      focussed on the carboxyterminal derivative (ANP 99-126) of the prohormone (ANP 1
      126), but recent evidence indicates that an additional peptide derived from ANP 1
      126, namely, ANP 31-67 also circulates, and has natriuretic actions. 2. The
      effects of ANP 31-67 on inner medullary collecting duct (IMCD) Na+ transport have
      been examined in freshly prepared suspensions of rabbit IMCD cells. Like ANP 99
      126, ANP 31-67 reduces Na+ transport in these cells. 3. However, unlike ANP 99
      126, this effect is not mediated by cGMP, and does not result from inhibition of
      apical Na+ channels. Rather, ANP 31-67 inhibits basolateral Na/K-ATPase, probably
      via the stimulation of PGE2 synthesis. 4. These results are discussed in the
      context of other natriuretic substances (interleukin 1 and endothelin), which
      also inhibit Na+ reabsorption by PGE2-mediated inhibition of Na/K-ATPase.

PMID- 7621603
TI  - Secretion and renal effects of ANF prohormone peptides.
AB  - 1. Atrial natriuretic factor (ANF) and pro ANF peptide appears to be secreted
      simultaneously from the atria in response to atrial stretch. 2. The major peptide
      forms secreted from rat atria appear to be ANF (pro ANF 99-126) as the primary C
      terminal peptide and pro ANF 1-30 as the primary N-terminal peptide, as opposed
      to 1-67 or 1-98. 3. The plasma concentrations of ANF and pro ANF 1-30 are
      increased by acute stimulation with blood volume expansion and the plasma levels
      of ANF and N-terminal ANF prohormone peptides are chronically elevated by high
      salt diet. 4. Pro ANF 31-67 produces a natriuresis which is not dependent on an
      increase in renal cGMP excretion, decreases in plasma renin activity (PRA) or
      elevations in plasma ANF concentration.

PMID- 7621605
TI  - Effects of ANF prohormone peptides in conscious primates.
AB  - 1. Recent studies suggest that amino-terminal peptides from the atrial
      natriuretic factor (ANF) prohormone are natriuretic. 2. The effects of pro ANF 31
      67 and ANF 99-126 on renal function were studied in conscious non-human primates
      (Macaca fascicularis). 3. Results show that pro ANF 31-67 and ANF 99-126 are
      diuretic and natriuretic and that when the two peptides are given in combination
      sodium excretion increases in an additive fashion. 4. These results indicate that
      multiple peptides from the ANF prohormone are natriuretic. Furthermore, these
      findings suggest that the combined action of these peptides causes the
      natriuresis that occurs after the release of endogenous atrial peptides.

PMID- 7621606
TI  - Atrial natriuretic peptide fragments in dogs with experimental heart failure.
AB  - 1. This study in the canine arteriovenous (AV) fistula model of high-output heart
      failure (HOHF) evaluated the chronic temporal changes in plasma ANF and pro ANF
      31-67 and their relationship to body-fluid balance and the renin-aldosterone
      axis. In addition, the haemodynamic, hormonal and renal excretory effects of
      synthetic pro ANF 31-67 infusions were examined in normal and AV fistula dogs
      with compensated HOHF. 2. Following the construction of the AV fistula, the dogs
      exhibited chronic parallel elevations in right atrial pressure and the plasma
      concentrations of ANF and pro ANF 31-67. The gradual increases in the two
      peptides were associated with a gradual decrease in plasma renin activity and the
      re-establishment of sodium balance. 3. In normal and compensated AV fistula dogs,
      synthetic pro ANF 31-67 produced similar significant reductions in arterial blood
      pressure, right atrial pressure and elevations in urinary sodium excretion. These
      effects were not associated with increases in plasma or urinary cyclic GMP
      (cGMP). 4. These results suggest that the elevation in the endogenous circulating
      levels of pro ANF 31-67 in the AV fistula dogs may represent one chronic adaptive
      mechanism to achieve body fluid homeostasis. Furthermore, via potentially
      different mechanisms of action, ANF and pro ANF 31-67 may coordinate and
      contribute to the regulation of haemodynamic and renal function during
      physiological and pathophysiological situations.

PMID- 7621607
TI  - Effects of pregnancy and progesterone metabolites on regulation of sympathetic
      outflow.
AB  - 1. Pregnancy is characterized by a 40% increase in blood volume and cardiac
      output, a decrease in arterial blood pressure and thus a substantial decrease in
      total peripheral resistance. The aims of the experiments described in this
      manuscript were: (i) to determine if pregnancy resulted in alterations in
      baroreflex control of sympathetic outflow; and (ii) to evaluate possible
      mechanisms for pregnancy-induced changes in control of sympathetic outflow. 2.
      Arterial baroreflex control of efferent renal sympathetic nerve activity was
      examined in female pregnant and non-pregnant normotensive Sprague-Dawley and
      Wistar-Kyoto rats. In both rat strains, pregnancy was associated with a decrease
      in baseline arterial pressure, a shift in the baroreflex function curve to a
      lower operating pressure range and an attenuated ability to reflexly increase
      sympathetic outflow above baseline levels during a hypotensive challenge.
      Pregnant Sprague-Dawley rats retained their ability to respond to a hypertensive
      challenge, whereas pregnant Wistar-Kyoto rats exhibited a decreased sensitivity
      to hypertensive as well as hypotensive challenges. 3. The inhibitory amino acid
      transmitter, GABA, mediates baroreflex sympatho-inhibition within the rostral
      ventral lateral medulla (RVLM) of the brainstem. Since 3 alpha-OH
      dihydroprogesterone (3 alpha-OH-DHP), a major metabolite of progesterone, is
      elevated in pregnancy and has been reported to potentiate central nervous system
      GABAA inhibitory responses, experiments were performed to determine if effects of
      this metabolite of progesterone could contribute to the pregnancy associated
      changes in control of sympathetic outflow.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7621608
TI  - Reflex regulation of hormonal responses during pregnancy.
AB  - 1. During pregnancy in most species, the resting levels of plasma angiotensin II,
      plasma ACTH (corticotropin) are increased. The concentration of vasopressin is
      also increased relatively to the osmolality in rats and in humans. 2. In the
      pregnant state mean arterial pressure is decreased, despite an increase in blood
      volume. Vasopressin and ACTH responses to hypotension are altered in pregnant
      ewes; the relationship between mean arterial pressure and vasopressin or ACTH
      response is shifted to the left, consistent with a change in set-point for
      regulation of mean arterial pressure. The vasopressin and cortisol responses to
      hypotensive haemorrhage are also altered in the pregnant dog; in this case the
      slope of the relation between mean arterial pressure and hormone response is
      decreased. 3. The decrease in hormone responses to hypotension is stimulus
      specific; ACTH responses to hypoglycaemia are increased in the pregnant ewe and
      AVP responses to hyperosmolality are not altered in the pregnant ewe. 4. The
      heart rate responses to hypotension are also decreased in pregnant ewes,
      consistent with the observation that baroreflex responses are decreased in the
      pregnant rat. 5. The data suggest that a change in regulation of arterial
      pressure alters the hormonal responses to hypotension in the pregnant state.

PMID- 7621609
TI  - Pregnancy attenuates activity of the baroreceptor reflex.
AB  - 1. Pregnancy-induced changes in acute blood pressure regulation are reviewed. 2.
      Pregnant animals are less able to maintain arterial pressure during haemorrhage
      than non-pregnant animals. 3. Baroreceptor reflex-mediated increases in heart
      rate, renal sympathetic activity, vasopressin, ACTH and cortisol are reduced
      during pregnancy. Therefore, one explanation for the subnormal ability of
      pregnant animals to regulate arterial pressure during haemorrhage is that the
      baroreceptor reflex is not as effective. 4. Chronic increases in oestrogen levels
      in non-pregnant rabbits do not reduce the gain of baroreflex control of renal
      sympathetic activity. This and other findings suggest that oestrogen alone does
      not mediate the blunted baroreflex activity observed during pregnancy.

PMID- 7621610
TI  - Control of intravascular volume during pregnancy.
AB  - 1. We wished to determine whether, during pregnancy, there is reduced renal
      response to atrial distension, whether secretion of atrial natriuretic factor
      (ANF) is suppressed and whether neural input from the atrial volume receptors to
      the central nervous system is altered. 2. Conscious, chronically instrumented
      female rats were used. Atrial distension was achieved by implanting small
      balloons positioned at the superior vena caval/right atrial junction; inflation
      of the balloon did not impede blood flow through the heart. 3. In virgin rats,
      atrial stretch caused increased urine volume, urine sodium and potassium output
      and decreased free water clearance. These responses were abolished during
      pregnancy. 4. In response to atrial stretch, plasma ANF levels increased
      significantly in virgin rats. No such secretory response was observed in the
      pregnant animals. 5. Distension of isolated atria derived from unmated and 7 day
      pregnant rats resulted in an increase in secretion of ANF into the perfusate.
      Atria from 14 and 21 day pregnant rats were unresponsive to distension. 6.
      Pretreatment with oestradiol (50 micrograms daily for 10 days) caused plasma ANF
      levels and ANF secretion by isolated perfused atria to increase. By contrast,
      testosterone pretreatment (15 mg twice weekly for 2 weeks) abolished stretch
      induced secretion of ANF by isolated atria. 7. C-fos activity in the
      paraventricular nucleus of virgin rats increased in response to atrial
      distension. This response was reduced in the 7 day pregnant rats and abolished at
      21 days. 8. We conclude that there is attenuation of both hormonal and neural
      responses to atrial distension in the pregnant animal. This allows blood volume
      to increase without eliciting homeostatic mechanisms to eliminate the extra
      fluid.

PMID- 7621611
TI  - Nitric oxide biosynthesis during pregnancy: implications for circulatory changes.
AB  - 1. The biosynthesis of NO and its second messenger, cGMP, increases from pre
      pregnant levels during rat gestation. An increase in plasma level and urinary
      excretion of cGMP is also evident during human pregnancy. However, the relative
      contribution of the maternal vasculature and other tissues to increased NO and
      cGMP biosynthesis during gestation is uncertain. Consensus is lacking about the
      contribution of NO to reduced maternal vascular tone and reactivity during
      gestation in various organ beds; clearly, further investigation is still needed.
      That NO may also regulate vascular smooth muscle behaviour during pregnancy by
      altering membrane potential is another intriguing possibility. 2. The
      syncytiotrophoblast of the human placenta expresses significant NO synthase
      activity, and along with the fetoplacental endothelium undoubtedly contributes to
      NO production during pregnancy. 3. Finally, it should be emphasized that vascular
      studies in gravid animal models need to be extended to pregnant women.

PMID- 7621612
TI  - How do fish oils affect vascular function?
AB  - 1. This is a review on the mechanisms by which fish oils affect vascular function
      and how such changes contribute to their documented cardioprotective effects. 2.
      Evidence that fish oils depress vascular responses to contractile agents will be
      examined. It is concluded that this effect of fish oils is mediated predominantly
      by alterations in prostanoid profile. 3. Effects of fish oils on arterial
      relaxation are discussed with particular emphasis on endothelium dependent
      relaxation. It is suggested that the functional impairment of endothelium
      dependent relaxation documented in a number of cardiovascular disease states can
      be reversed by dietary fish oils. 4. In addition, possible effects of fish oils
      on growth factors, inositol trisphosphate and lipid metabolism, the sympathetic
      nervous system, rheological and membrane properties and inducible nitric oxide
      are reviewed.

PMID- 7621613
TI  - Direct effects of angiotensin I, angiotensin II, an ACE inhibitor and a serine
      proteinase inhibitor on cultured heart cells from spontaneously hypertensive
      rats.
AB  - 1. The purpose of the present study was to investigate how angiotensin I (AI),
      angiotensin II (AII), an angiotensin converting enzyme inhibitor (ACE inhibitor;
      ACE-I) and a serine proteinase inhibitor contribute to the protein metabolism of
      cultured newborn spontaneously hypertensive rats (SHR) heart cells. We examined
      the uptake of [3H]-uridine and [3H]-proline into cultured cardiac myocytes and
      fibroblasts, respectively. 2. Both AI and AII increased the uptake of [3H]
      uridine into myocytes in a concentration-dependent manner. However, the effect of
      AI was denied in the presence of the ACE-I with the concentration of 10(-6) g/mL.
      Both AI and AII increased the uptake of [3H]-proline into cardiac fibroblasts in
      a concentration-dependent manner. However, this effect was only partially
      abolished in the presence of 10(-6) g/mL of the ACE-I, which was the maximal
      concentration that did not exert any effect on the [3H]-proline uptake. In the
      presence of AII receptor antagonist, [Sar1, Leu8]-AII, the uptake of [3H]-proline
      into cardiac fibroblasts was completely inhibited. Moreover, the stimulatory
      effects of AI on the uptake of [3H]-proline into cardiac fibroblasts were
      completely inhibited in the presence of a serine proteinase inhibitor in addition
      to the ACE-I. 3. These results suggest that an ACE-I has different effects on
      protein metabolism in the heart and also suggest the presence of serine
      proteinase in cultured cardiac fibroblasts from SHR.

PMID- 7621614
TI  - Changes in intra- and extracranial tissue blood flow upon stimulation of a
      reticular area dorsal to the facial nucleus in cats.
AB  - 1. A small area in the dorsal part of the lateral tegmental field specifically
      responsible for the increase of blood flow in the common carotid artery (CCA)
      without accompanying change in the resting blood pressure was first identified in
      our laboratory. Since the area is located just dorsal to the facial nucleus, we
      named it the dorsal facial area (DFA; Kuo et al. 1987). 2. The purpose of this
      study was to clarify whether an increase of blood flow in intra- and/or
      extracranial tissues was responsible for the increase in CCA blood flow upon DFA
      stimulation, and to determine the role of cholinergic transmission in this
      response. 3. In 20 cats under chloralose and urethane anaesthesia, microsphere
      reference flow technique was used to measure the regional blood flow of intra-
      and extracranial tissues. 4. Electrical stimulation of the DFA appeared to
      increase the regional blood flow of both cerebral hemispheres (intracranial
      tissues) and to increase predominantly the regional blood flow of extracranial
      tissues on the side ipsilateral to stimulation. Increases in the regional blood
      flow of intracranial tissues were enhanced after i.v. administration of atropine
      but reduced with physostigmine. In contrast, increases in the regional blood flow
      of extracranial tissues were reduced after i.v. atropine but enhanced after
      physostigmine. 5. These findings suggest that DFA stimulation may promote the
      release of ACh in intra- and extracranial vessels. The muscarinic action may
      restrict the DFA-induced increase in blood flow of intracranial tissues, but
      enhance that of extracranial tissues.

PMID- 7621615
TI  - Effects of NG-nitro-L-arginine on pressure natriuresis in anaesthetized rabbits.
AB  - 1. We tested the effects of blockade of nitric oxide synthesis on renal function
      under conditions of controlled renal artery pressure. Our hypothesis was that
      endogenous nitric oxides plays a role in the natriuresis that accompanies
      increased renal perfusion pressure. We used a novel technique which employed an
      extracorporeal circuit to produce step changes over a wide range of renal artery
      pressures in pentobarbitone-anaesthetized rabbits. 2. Rabbits were treated with
      either NG-nitro-L-arginine (NOLA, 20 mg/kg, i.v.; n = 8) or its vehicle (n = 8).
      Renal artery pressure was set (by adjusting the extracorporeal circuit) at 65,
      80, 95, 110 and then 130 mmHg respectively, at the beginning of each of five 30
      min experimental periods. 3. NOLA treatment caused profound renal
      vasoconstriction that was largely independent of the level of renal artery
      pressure, renal blood flow being 35-43% lower in NOLA-treated than in vehicle
      treated rabbits across the range of renal artery pressures tested (P = 0.002).
      NOLA treatment increased filtration fraction (P = 0.02), and tended to reduce
      glomerular filtration rate (P = 0.09). 4. NOLA-treatment affected sodium
      excretion in a manner dependent on the legel of renal artery pressure, with the
      slope of the relationship between sodium excretion and renal artery pressure
      being lower in NOLA-treated than in vehicle-treated rabbits (P = 0.006). 5. These
      data provide direct evidence that in anaesthetized rabbits endogenous nitric
      oxide (i) tonically dilates the renal vasculature across a wide range of renal
      perfusion pressures, and (ii) enhances sodium excretion to a progressively
      greater degree as renal artery pressure is increased.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7621616
TI  - Urinary beta 2-microglobulin levels and urinary N-acetyl-beta-D-glucosaminidase
      enzyme activities in early diagnosis of non-insulin-dependent diabetes mellitus
      nephropathy.
AB  - To assess whether urinary N-acetyl-beta-D-glucosaminidase (NAG) and beta 2
      microglobulin (beta 2-MG) levels could be used as predictors of diabetic
      nephropathy or not, 59 non-insulin-dependent diabetes mellitus (NIDDM) patients
      were included in our study (31 females, 29 males; mean age 54 +/- 10.1). The
      control group consisted of 20 healthy non-diabetic subjects (12 males and 8
      females; mean age 47 +/- 13.9). The patients in the study group were classified
      according to the duration of diabetes. In all cases, urinary beta 2-MG levels
      were measured by specific enzyme immunoassays and urinary NAG enzyme activities
      were determined by colorimetric methods. The mean urinary NAG level in study
      group was higher than that of the control group (p < 0.01). It was observed that
      NAG activity begins to rise in the third year of NIDDM, makes a plateau between 3
      10 years, and rapidly increases after the 10th year. No significant difference in
      NAG activity was found between chemical NIDDM and control groups. No significant
      difference in beta 2-MG levels was found between study and control groups. The
      mean NAG activity in patients with early glomerular hyperfiltration was
      significantly higher than those without early hyperfiltration and control group
      (p < 0.05), whereas the mean beta 2-MG level was not. As a result, urinary NAG
      enzyme activity significantly increases, while urinary beta 2-MG level remains
      unchanged in patients with NIDDM. It was concluded that measurement of urinary
      NAG enzyme activity may be a good indicator in early diagnosis of diabetic
      nephropathy.

PMID- 7621617
TI  - A monoclonal antibody based enzyme-linked immunosorbent assay for the
      determination of GAD65, the smaller isoform of glutamic acid decarboxylase.
AB  - An enzyme-linked immunosorbent assay for GAD65, the smaller form of glutamic acid
      decarboxylase and an important autoantigen related to Type 1 diabetes, is
      described. The competitive binding assay is based on a monoclonal antibody
      specifically reactive with GAD65. The assay is suitable for quantification of
      this enzyme between 40 and 300 pg/microliter. The intraassay coefficients of
      variation (cv) are between 5.6% and 8.9% and the interassay cvs lie between 9.4%
      and 17.3%. The covalent binding of the antigen to magnetic beads as the solid
      phase makes the assay also applicable for quantification of GAD65 in tissue
      homogenates with a high concentration of detergent. The GAD65 content of islets
      isolated from newborn Lewis rat was detected to be 310 pg/islet. However, GAD65
      was not detectable in mouse islets.

PMID- 7621618
TI  - A comparison of the metabolic profiles of fetal and maternal plasma and placenta
      in normal and diabetic rats by 1H magnetic resonance spectroscopy.
AB  - Spectral analysis of spin-echo 1H magnetic resonance spectroscopy (MRS) data has
      revealed differences in the metabolic profiles of maternal and fetal plasma and
      placental extracts. Resonances from low-molecular weight components of the normal
      maternal and fetal plasma were attributed to glucose, lactate, creatine, citrate,
      amino acids and ketone bodies. There were also signals from lipoprotein molecules
      associated with lipid-transporting moeties contained in the plasma. The placental
      extract showed a similar composition to the plasma samples however the spectra
      were dominated by a large signal attributed to betaine, there was also an absence
      of signals from citrate, acetoacetate, acetone and lipoproteins. Diabetes caused
      profound changes in all tissue types indicating high levels of glucose and
      ketogenic activity. In both the maternal and fetal plasma there were increases in
      glucose, ketone bodies and valine in the diabetic rats, increases in lactate and
      alanine were confined to the fetal plasma and placenta. This study indicates that
      diabetes causes major changes in the composition of fetal plasma which in turn
      could interfere with the development of the fetus.

PMID- 7621619
TI  - Hypoglycemic effects of three plants from eastern Himalayan belt.
AB  - Rhizome of Costus speciosus, tuber of Nephrolepsis tuberosa, and bulb of
      Stephania hernandifolia, used by the local people and traditional healers in the
      Eastern Himalayan belt, were studied for their effects on serum glucose levels in
      nondiabetic and diabetic rat models at different prandial states. The results
      showed that in nondiabetic rat C speciosus and N tuberosa had no significant
      effect in the fasting or postprandial state when freeze-dried juices were fed
      simultaneously with glucose. However, when fed 30 min before the glucose load
      both C speciosus (p < 0.05) and N tuberosa (p < 0.003) showed hypoglycemic
      effect. To the contrary, S hernandifolia increased the serum glucose levels of
      nondiabetic rats in all the series of experiments (p < 0.05 or p < 0.01). In
      NIDDM model rats N tuberosa opposed the rise in serum glucose level when it was
      fed 30 min before the glucose load (p < 0.02), whereas S hernandifolia had a
      tendency to raise the serum glucose level. In IDDM model rats, none of these
      three freeze-dried juice showed any effect in the fasting state. However, C
      speciosus showed significant hypoglycemic effect (p < 0.002) when the juice was
      fed with simultaneous glucose load. In marked contrast to the findings with
      nondiabetic and NIDDM model rats S hernandifolia showed significant hypoglycemic
      effect (p < 0.05-0.006) in both the stages (fed simultaneously with, and 30 min
      before the glucose load) of prandial states of the IDDM model rats. The results
      indicated that these three plants have interesting possibilities as a source of
      oral hypoglycemic agents.

PMID- 7621620
TI  - The effect of STZ-induced diabetes on serum triiodothyronine (T3) and thyroxine
      (T4) levels in the rat: a seven week time course.
AB  - This study examined the effect of a seven week period of diabetes on serum
      triiodothyronine (T3) and thyroxine (T4) levels in male Sprague-Dawley rats.
      Diabetes was induced by a sublingual injection of streptozotocin (80 mg/kg) in
      one-half of the animals (D) while the other half of the animals received a sham
      injection of 40mM citrate (pH 4.5) (C). Blood was sampled weekly via a cardiac
      puncture and serum T3 and T4 levels were determined by radioimmunoassay
      (Pharmacia) techniques. For the first two weeks after diabetes inducement T3
      levels were significantly (p < or = .05) less in the D animals, after which time
      T3 levels did not differ significantly (p < or = .05) between the two groups. A
      significant (p < or = .05) decrease in serum T4 levels occurred by the first week
      of diabetes and was sustained through the seventh week. T3:T4 ratio was
      significantly (p < or = .05) higher in the diabetic animals at weeks 2 and 5.
      These findings suggest that the organism attempts to maintain levels of the more
      biologically active of the two thyroid hormones, T3, at the expense of
      circulating levels of serum T4 during prolonged states of STZ-induced diabetes.

PMID- 7621621
TI  - Calibration of erythrocyte mean cell volume.

PMID- 7621622
TI  - Automated cell counters: quality control.

PMID- 7621623
TI  - Two-centre evaluation of the Abbott CD3500 blood counter.
AB  - The CD3500 blood counter (Abbott Laboratories) is a 33 parameter fully automated
      blood counter that produces a five part differential count with flagging of
      leucocyte abnormalities. In this evaluation excellent correlation between CD3500
      and Coulter STKR blood counter was found for all red cell and platelet parameters
      on the 221 samples tested. Studies of carryover, mixing efficiency and precision
      also gave excellent results. There was a good correlation with manual 400 cell
      differential counts for neutrophils, lymphocytes, monocytes and eosinophils for
      the 468 samples compared. Correlation of CD3500 and manual basophil counts was
      poor. Normal samples stored at 4 degrees C and analysed while cold showed
      satisfactory stability for WBC, RBC, Hb, MCV and platelets for 48 h and a stable
      differential for 24 h. Correlation with the differential count produced by the
      Coulter STKS showed good correlation for neutrophils, lymphocytes, monocytes and
      eosinophils; correlation with STKS basophils was poor. False positive flagging
      rate varied between 8.9% (Band and/or IG) and 0.9% (NRBC) depending on the nature
      of the flag; 5.8% of samples exhibited two or more false positive flags. No
      significant breakdowns were encountered during the period of the evaluation. The
      scatterplot displays of laser light scatter produced by the instrument provide an
      interesting adjunct to conventional morphology.

PMID- 7621624
TI  - Improved automated leucocyte counting and differential in newborns achieved by
      the haematology analyser CELL-DYN 3500.
AB  - Automated leucocyte counts in newborns generated by the impedance principle are
      artificially affected by the high osmotic resistance of some newborn RBC and
      possibly by the high normoblast numbers present during the neonatal period.
      Erroneously high WBC counts may result. The haematology analyser CELL-DYN 3500
      (Abbott Diagnostika GmbH, Wiesbaden-Delkenheim, Germany) has two different
      channels for the WBC count, an electrical resistivity (impedance) channel and a
      laseroptical channel. In combination with facultative extended lysis of resistant
      RBC before WBC count, this instrument is claimed to be very suitable for newborn
      blood analysis. We measured the WBC count and differential of 165 blood samples
      from newborns and cord blood on the CELL-DYN 3500. Reticulocyte count and manual
      differential including normoblasts were determined. Furthermore, some technical
      aspects of neonatal blood analysis were evaluated: precision, cell stability,
      effect of incorrect blood-anticoagulant ratio of small blood collecting tubes.
      The internal decision making process of the CELL-DYN 3500 selects the result
      either from the optical channel (identifies and excludes normoblasts) or from the
      resistivity channel (eliminates resistant RBC). This instrument gives a reliable
      and accurate WBC count and differential of neonatal samples even in blood samples
      with normoblasts and lytic resistant RBC. The result given by the CELL-DYN 3500
      can be confirmed by a subsequent run in extended lyse mode.

PMID- 7621625
TI  - Guidelines on the provision of facilities for the care of adult patients with
      haematological malignancies (including leukaemia and lymphoma and severe bone
      marrow failure). British Committee for Standards in Haematology Clinical
      Haematology Task Force.
AB  - This report defines four levels of care required for the management of adult
      patients with haematological malignancies and marrow failure (acute and chronic
      leukaemias, lymphomas, myelodysplastic and myeloproliferative disorders, myeloma
      and severe aplastic anaemia). The higher levels of care require increasing
      specialist expertise, staffing and resources. Staffing includes both the medical,
      nursing and scientific/laboratory professions and other support staff. Resources
      include ward provision, bed numbers, equipment, laboratory and radiotherapy
      facilities, pharmacy, support services and research. Blood transfusion services
      and their organisation are discussed separately. The guidelines indicate to
      providers and purchasers the issues to be considered in placing contracts for the
      care of these patients. A glossary of terms is provided for purchasers.

PMID- 7621626
TI  - Discriminant function using red cell indices to distinguish between HbC and HbE
      traits.
AB  - Values for MCV, MCH, MCHC and red cell distribution width (RDW) derived from
      subjects with HbC and HbE traits using a Technicon H*1 automated blood count
      analyser were compared. Significantly higher MCH, MCHC and RDW values were found
      in those with HbC trait. By use of a simple discriminant function (MCHC2 x
      RDW/1000), 19/20 subjects with HbC trait gave a value > or = 16.3, and 20/21
      subjects with HbE trait gave a value < or = 16.2. The function described may be
      of value as an adjunct to electrophoresis in intralaboratory quality control.

PMID- 7621627
TI  - A comparison of five commercial thromboplastins: ISI re-evaluation on an
      automated coagulometer.
AB  - Five commercial rabbit brain thromboplastins were compared with an International
      Reference Preparation on an ACL coagulometer, using 90 patients stabilized on
      warfarin and 22 normal individuals. The prothrombin times were converted to INRs
      using the thromboplastin manufacturers' quoted ISI. The quoted ISIs were
      reassigned using orthogonal regression analysis and then used to recalculate INRs
      for patient and commercial INR control plasmas. This showed that the
      manufacturers' quoted ISIs and the INR control plasma results were inconsistent.
      With one thromboplastin the manufacturers quoted ISI changed from 1.17 to 1.05
      whilst the control plasma results changed from an INR of 4.3 to an INR of 3.7
      (manufacturer's INR, 3.3). In most routine laboratories ISI reassignment is not
      practical. We conclude that the availability of a reliable plasma calibrant is
      essential for the accurate calculation of INRs at a local level.

PMID- 7621628
TI  - Hypofibrinogenaemia is the commonest congenital fibrinogen abnormality in north
      India.
AB  - Congenital abnormalities of fibrinogen are rare disorders and all the cases
      reported in the literature indicate that the incidence of afibrinogenaemia is
      much higher than hypofibrinogenaemia. Of the total of 20 cases reported from
      other parts of India only one was congenital hypofibrinogenaemia. In contrast,
      the present study showed eight patients with congenital hypofibrinogenaemia among
      a total of nine unrelated North Indian patients with a fibrinogen abnormality.
      This disproportionately high incidence of hypofibrinogenaemia suggests the
      existence of a distinct genetic defect in the North Indian population.

PMID- 7621629
TI  - Platelet size analysis in the quality assurance of platelet concentrates for
      transfusion.
AB  - The platelet distribution width (PDW) as analysed on standard haematology cell
      counters is an indicator of size dispersion in the platelet population. Using a
      Sysmex E-2500 analyser platelet concentrates prepared for transfusion showed an
      increase in PDW over storage. This increase correlated strongly with in vitro
      indicators of platelet viability (pH and response to osmotic stress). PDW may
      thus be useful for clinical haematology laboratories as a predictor of the
      viability of transfused platelets. The same instrument gave a measure of the
      largest platelets in the platelet population as a large cell ratio (P-LCR). For
      platelet concentrates with less than 8 x 10(10) platelets/unit, the P-LCR at
      preparation was negatively associated with the end of storage pH, indicating that
      the presence of large platelets increases the production of lactic acid and
      accelerates the platelets' metabolic storage lesion. This information may be
      useful in determining storage conditions for single donor platelets harvested by
      apheresis.

PMID- 7621630
TI  - Changes in maternal plasma macrophage-colony stimulating factor levels during
      normal pregnancy.
AB  - An enzyme-like immunosorbent assay and a blood autoanalyser were used to
      determine macrophage-colony stimulating factor (M-CSF) levels and the absolute
      number and percentage of circulating monocytes in 80 normal women with singleton
      pregnancies at 12-40 weeks' gestation, and ten healthy non-pregnant volunteers.
      The mean values of M-CSF and absolute number and percentage of circulating
      monocytes of the control group were 367 U/ml (SD 43) and 389 x 10(6)/l (SD 180)
      and 5.3% (SD 1.7) respectively. In pregnancy, M-CSF was significantly higher than
      non-pregnant controls only after 28 weeks' gestation. The absolute number and the
      percentage of circulating monocytes increased significantly with gestation after
      16 weeks. There was no significant association between the concentration of M-CSF
      and the number or percentage of circulating monocytes. These data suggest that
      during pregnancy there is an up-regulation of M-CSF and monocytes.

PMID- 7621631
TI  - High serum levels of granulocyte-macrophage colony-stimulating factor in patients
      with liver cirrhosis and granulocytopenia.
AB  - Leucopenia is often observed in patients with liver cirrhosis. We measured levels
      of serum granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients
      with liver cirrhosis by a sensitive enzyme linked immunosorbent assay. Eight out
      of 22 patients with liver cirrhosis had detectable serum GM-CSF (range, 55 to 245
      pg/ml:mean, 135 pg/ml). Serum GM-CSF was detected in all patients with a
      granulocyte count below 2.0 x 10(9)/l, but in only one patient with a granulocyte
      count above 2.0 x 10(9)/l. Haemoglobin concentration, platelet count, serum
      albumin, total bilirubin and aminotransferase levels did not correlate with serum
      GM-CSF levels. These findings may reflect a feedback mechanism between the number
      of circulating granulocytes and serum GM-CSF levels in patients with cirrhosis.

PMID- 7621632
TI  - Immunostaining of whole agar cultures by APAAP.
AB  - We have adapted the alkaline phosphatase-anti alkaline phosphatase (APAAP)
      technique to demonstrate cell antigen distributions in intact agar culture. The
      method facilitates batch processing and is no less convenient to perform than
      standard APAAP procedures. Myeloid and lymphoid antigens generally demonstrated
      strong staining intensity. However, staining at day 0 consistently produced no
      antigen expression for two monoclonals (CD11c and CD34) in contrast to positivity
      in parallel cytospins. CD11c showed rapidly increasing antigen expression over
      subsequent days of culture whereas the expression of CD34 could not be shown in
      conventional agar culture at any time from day 0 to day 14. Positivity was only
      restored in CD34-positive leukaemic cells using a modified culture technique in
      which cells were cultured as pre-formed small aggregates. Assessment of these
      aggregates extended to cell cycle analysis using anti-bromodeoxyuridine. CD71
      positivity in normal culture samples correlated with colony configuration
      (whether clones were 'spread' or 'tight' in appearance). CD38 staining of normal
      bone marrow culture at day 7 showed asymmetrical staining of cells in a small
      number of micro-groups. The clonal detection of aberrant antigens (CD7, CD2) for
      assessment of minimal residual disease in AML was a disappointment due to the
      relative frequency of positive clones in normal culture.

PMID- 7621633
TI  - Teicoplanin and oral ciprofloxacin as outpatient treatment of infective episodes
      in patients with indwelling central venous catheters and haematological
      malignancy.
AB  - Central venous catheters are often the focus of microbial colonization which may
      cause bacteraemia (or fungal septicaemia) in both neutropenic and non-neutropenic
      patients. Such episodes are associated with considerable morbidity and may
      require admission to hospital or replacement of the central line. We have used
      the combination of intravenous teicoplanin and oral ciprofloxacin to treat such
      episodes as outpatients, achieving a salvage rate of 74%. Seven of thirty-five
      episodes resulted in removal of the line. The treatment was well tolerated and
      well-suited to the day ward setting.

PMID- 7621634
TI  - Randomized trial of intravenous immunoglobulin prophylaxis for patients with
      chronic lymphocytic leukaemia and secondary hypogammaglobulinaemia.
AB  - Forty-two patients with chronic lymphocytic leukaemia (CLL), serum IgG levels <
      5.5 milligrams and a history of two or more recent infections, were randomized to
      receive infusions of 18 g human intravenous immunoglobulin (IVIg) or human
      albumin placebo every three weeks. During the 12 month study 122 infections were
      documented but only four were associated with neutropenia. Ten patients (24%)
      with IgG levels < 3.0 milligrams experienced 65% of the infections. In response
      to IVIg there were immediate and accumulative increases in serum IgG levels and
      an associated decrease in total and serious infections. If three further
      infections occurred, placebo patients were commenced on 18 g IVIg, and IVIg
      patients were increased to 24 g IVIg. Approximately 50% of these cases
      subsequently remained infection free. The study shows the usefulness of
      prophylactic Sandoglobulin in CLL patients with hypogammaglobulinaemia, and
      suggests that this may be justified in those with recurrent infections and serum
      IgG levels < 3 milligrams.

PMID- 7621635
TI  - Evaluation of the gel test for antibody screening in a tertiary hospital in Hong
      Kong; insensitivity for some cold antibodies that are reactive at 37 degrees C by
      conventional indirect antiglobulin tests.
AB  - The antiglobulin gel test (DiaMed) was compared with conventional IAT methods in
      pretransfusion antibody screening in a tertiary hospital in Hong Kong. Antibody
      titrations showed that the gel system was more sensitive than the tube IAT method
      in detecting anti-D, anti-S, anti-s, but slightly less sensitive with anti-E. The
      gel tests detected all clinically significant warm reacting allo-antibodies
      detected by conventional IAT methods except one case of weak anti-E. It detected
      a case of anti-C missed in conventional screening. The number of serological
      investigations due to false positive screens, non-specific antibodies and
      clinically insignificant cold antibodies (anti-P, and anti-Lewis) were reduced.
      The gel system was fast and easy to use. It would reduce delays and inconvenience
      caused to patients due to false positive screens and non-specific antibodies
      without compromising detection of clinically significant antibodies. However, of
      concern was the failure to detect several cases of anti-Le(a) and anti-P1 that
      were reactive at 37 degrees C by conventional IAT and one case of anti-H in a
      patient with Parabombay A.

PMID- 7621636
TI  - Changing concepts in investigations of haemostasis.

PMID- 7621637
TI  - Thrombocytopenia and spontaneous rupture of the spleen associated with infectious
      mononucleosis.
AB  - Infectious mononucleosis (IM) normally has a benign, self-limiting course.
      Thrombocytopenia and spontaneous rupture of the spleen are two separate
      complications of the illness. We describe a patient who suffered from both these
      complications.

PMID- 7621638
TI  - IgA lambda myeloma presenting concurrently in identical twins with subsequent
      transformation to 'aggressive phase' in one.

PMID- 7621639
TI  - Autoimmune haemolytic anaemia associated with ciprofloxacin.

PMID- 7621640
TI  - DVT following oral contraceptive therapy in association with homozygous factor V
      Leiden.

PMID- 7621641
TI  - Parameter estimation in six numerical models of transperitoneal transport of
      potassium in patients undergoing peritoneal dialysis.
AB  - The mechanisms of transperitoneal potassium transport during peritoneal dialysis
      were evaluated by validation of different mathematical models. The models were
      designed to elucidate the presence or absence of diffusive, non-lymphatic
      convective and lymphatic convective solute transport. Experimental results were
      obtained from 26 non-diabetic patients undergoing peritoneal dialysis. The
      validation procedure demonstrated that models including both diffusive and non
      lymphatic convective solute transport were superior to the other models.
      Lymphatic convective solute transport was not identifiable. Furthermore, it was
      demonstrated experimentally that the equilibrium distribution of potassium
      between plasma water and dialysate did not differ from a Donnan equilibrium,
      although the precondition of the Donnan equilibrium was not fulfilled, i.e. the
      volumes on each side of the membrane were not constant and dialysate was not an
      ultrafiltrate of plasma.

PMID- 7621642
TI  - Variation in plethysmographically measured limb blood flow using two study
      designs.
AB  - Ingestion of food is known to influence peripheral blood flow. In clinical drug
      trials it is important to obtain values which do not fluctuate because of
      exogenous factors. In the study reported here, the variability of limb blood flow
      was assessed using two study designs: after a light standard breakfast with
      nothing more to eat (Day A); and after an overnight fast followed by a heavy non
      standardized lunch (Day B). Calf and forearm blood flow (BF), venous capacity
      (VC) and maximal venous outflow (MVO) were measured by means of strain-gauge
      venous occlusion plethysmography in 10 young healthy subjects six times during a
      period of 8 h. The most stable values were recorded from the calf on Day A, when
      no statistically significant variation occurred in any of the parameters. Mean
      values for calf BF ranged from 3.9 to 4.3 ml min-1 100 ml-1 (SEM 0.3-0.4) at the
      different time points on Day A. The corresponding values for VC were 3.4-3.7 ml
      100 ml-1 (SEM 0.2-0.3) and for MVO were 100-112 ml min-1 100 ml-1 (SEM 7-10).
      Within-subject coefficients of variation were 13-16%. After lunch on Day B, both
      calf and forearm BF increased significantly, by 40-60%, as compared with prelunch
      values, and remained at about this level throughout the rest of the day. The
      corresponding postlunch increase in VC was 25-40%, and that in MVO was 20-25%. A
      study design in which the subjects ate a light, standard breakfast before the
      start of measurements and fasted thereafter gave fairly stable plethysmographic
      results.

PMID- 7621643
TI  - Variability in airway conductance and lung volume in subjects with asthma.
AB  - Variability in airway conductance (Gaw) and lung volume (TGV) was studied in 26
      subjects with moderately severe asthma during a 9-week period. Specific airway
      conductance (SGaw) was calculated as Gaw:TGV. There was considerable inter
      individual variability in airway conductance, and a smaller variability in TGV.
      Airway conductance (SGaw) showed an eight-fold difference and TGV a three-fold
      difference between smallest and largest values. The intra-individual variability
      was less, with a range of +/- 55% (SGaw) and +/- 12% (TGV) of the grand mean,
      respectively. The error of the method contributed only marginally to the
      variations in airway conductance. These data for spontaneous variability of
      conductance facilitate, for example, the assessment of the clinical importance of
      changes in lung function seen after exposure to air pollutants in chamber
      studies. Furthermore, the substantial inter-individual variability in conductance
      argues against comparing samples of asthmatic subjects in polluted and non
      polluted areas, and in favour of prospective studies of cohorts of subjects with
      asthma.

PMID- 7621644
TI  - Beat-to-beat agreement of non-invasive finger artery and invasive radial artery
      blood pressure in hypertensive patients taking cardiovascular medication.
AB  - The aim of this study was to investigate and quantify the agreement between
      simultaneous and ipsilateral non-invasive finger artery blood pressure (Finapres)
      and intra-arterial radial blood pressure among 13 volunteer hypertensive
      patients, aged 36-71 years and taking cardiovascular medication, during steady
      state fluctuation of arterial blood pressure and during an increase in blood
      pressure induced by static exercise. Eight patients were being treated with beta
      blocking agents, eight with calcium antagonists, four with angiotensin-converting
      enzyme inhibitors, four with diuretics and one with prazosin in combination
      therapy. Their auscultatory brachial artery blood pressures ranged in systole
      from 142 to 206 mmHg and in diastole from 88 to 120 mmHg during the treatment.
      The mean systolic finger artery blood pressure deviated by -14 +/- 5 mmHg (P =
      0.02, mean value +/- SEM) and the diastolic finger artery blood pressure deviated
      by 0.6 +/- 3 mmHg (P = 0.70) from the corresponding radial artery pressure. The
      maximal beat-to-beat difference between systolic and diastolic finger and radial
      artery pressure, respectively, showed that a range of less than 10 mmHg in the
      steady state after individual adjustment for bias. In general, neither systolic
      nor diastolic differences between the methods exceeded the limits of +/- 10 mmHg,
      and the bias did not significantly increase (P > or = 0.12) during a 10-mmHg
      increase in arterial blood pressure caused by static exercise. Among three
      subjects, an increase in bias and poorer agreement was associated with atrial
      fibrillation and steplike changes in the Finapres output after autocalibration.
      The results support usage of the Finapres technique to measure beat-to-beat
      changes of peripheral arterial blood pressure in hypertensive patients taking
      cardiovascular medication, with a feasible agreement with beat-to-beat radial
      artery blood pressure.

PMID- 7621645
TI  - Effects of glucocorticoids and sympathomimetic agents on basal and insulin
      stimulated glucose metabolism.
AB  - The mechanisms responsible for glucocorticoid-induced insulin resistance remain
      unclear. Glucocorticoids show several interactions with the sympatho-adrenal
      system which may contribute to this decrease in insulin sensitivity: they enhance
      the synthesis and actions of catecholamines, but abolish insulin-induced
      activation of muscle sympathetic nerve activity. The present study was performed
      in order to investigate the effects of the interactions between glucocorticoids
      and the sympatho-adrenal system on insulin sensitivity. Basal and insulin
      stimulated glucose metabolism was measured in healthy human subjects during four
      2-h clamp studies as follows: control (C); after taking oral dexamethasone (2 mg
      daily) for 2 days (D); after taking oral ephedrine sulphate (40 mg daily) for 2
      days (E); and after taking dexamethasone+ephedrine (D+E). Glucose uptake,
      production and oxidation were calculated from plasma 13C glucose and exhaled
      13CO2 during constant tracer infusion of U-13C glucose. Basal glucose production,
      utilization and oxidation were similar in all four studies. During
      hyperinsulinaemia, glucose uptake was reduced by 51.5% with treatment D, by 25.9%
      with treatment E, and by 49.6% with D+E. Glucose oxidation was reduced by 54.0%
      with treatment D, by 24.0% with treatment E, and by 57.2% with D+E. Hepatic
      glucose production was completely suppressed in all four studies. It is concluded
      that both dexamethasone and ephedrine decrease insulin-mediated glucose uptake
      and oxidation. Co-administration of ephedrine does not suppress the
      glucocorticoid-induced alterations of glucose metabolism. This indicates that
      glucocorticoid-induced insulin resistance is not related to the inhibition of
      muscle sympathetic nerve activity. These results suggest instead that
      glucocorticoids and sympathomimetic agents may impair glucose metabolism by
      common actions.

PMID- 7621646
TI  - Modification and validation of a commercially available portable detector for
      measurement of adipose tissue blood flow.
AB  - Adipose tissue blood flow is measured from the clearance of radioactive xenon
      from a depot. Traditionally, a NaI detector has been used to measure the residual
      depot of xenon. However, this is sensitive to movement artefacts. We tested a
      commercially available lightweight CsI detector which can be strapped to the
      anterior abdominal wall. In pilot studies the CsI detector produced higher values
      for adipose tissue blood flow than did a conventional NaI detector. It was
      modified by inclusion of spacers to distance it from the skin. Flow results
      generated by the modified detector were similar to those generated by the NaI
      detector, both after an overnight fast and during the increased blood flow after
      a meal. Individual decay patterns generated by the CsI detector were, however,
      significantly smoother than those from the NaI detector.

PMID- 7621647
TI  - Cardiovascular response in patients with and without myocardial ischaemia during
      dobutamine echocardiography stress test for coronary artery disease.
AB  - Dobutamine is widely used in cardiac stress testing for coronary artery disease
      and myocardial viability. To assess the systemic cardiovascular response during
      dobutamine echocardiography stress testing, we investigated nine patients without
      myocardial ischaemia (group 1, aged 48 to 72 years) and nine patients with
      myocardial ischaemia during the test (group 2, aged 53 to 73 years), by use of
      Doppler/echocardiography and subclavian artery pulse trace calibrated with
      brachial artery pressures. Peripheral resistance, total arterial compliance, and
      aortic characteristic impedance were estimated using a 3-element windkessel model
      of the systemic circulation. During infusion of dobutamine up to 40 micrograms kg
      1 min-1, arterial pressure was maintained near baseline levels, whereas heart
      rate and cardiac index increased, more so in group 1 (mean: 89 and 79%) than in
      group 2 (58 and 52%; P < 0.05 vs. group 1). Peripheral resistance was decreased
      by > or = 32% at peak stress, whereas characteristic impedance was maintained at
      or above baseline in both groups, and total arterial compliance was not
      significantly altered. The cardiovascular response in group 2 was not influenced
      by the wall motion abnormalities. Thus, in these patients the inotropic,
      chronotropic, and vasodilatory effects of dobutamine balanced the ischaemic
      impairment of left ventricular function during the stress test.

PMID- 7621648
TI  - Saline contrast and colour Doppler transoesophageal echocardiography in detecting
      a patent foramen ovale and right-to-left shunts in stroke patients.
AB  - A paradoxical embolism due to right-to-left shunt through a patent foramen ovale
      (PFO) can be responsible for stroke and other ischaemic cerebral events. We
      studied the usefulness of saline contrast transoesophageal echocardiography after
      the Valsalva manoeuvre in detecting PFO and right-to-left shunts in 28 adult
      patients without known reason for a recent stroke. The results were compared with
      conventional transthoracic colour Doppler and with transoesophageal colour
      Doppler techniques. A PFO was found in 24 patients (86%) of our selected study
      population, whereas in four patients no PFO was found. A PFO with left-to-right
      shunt could be diagnosed by transthoracic colour Doppler echocardiography in only
      one case. A PFO with left-to-right shunt was found by transoesophageal colour
      Doppler echocardiography in 17 patients (61%), but in only three of them was a
      right-to-left shunt detected, even after the Valsalva manoeuvre. In contrast, a
      PFO with right-to-left shunt could be detected in 21 patients (75%) by using
      saline contrast transoesophageal echocardiography with the Valsalva manoeuvre.
      However, the method was unable to detect three cases of PFO with only left-to
      right shunt, which were detected by colour Doppler transoesophageal
      echocardiography. In conclusion, our results show that saline contrast
      transoesophageal echocardiography with the Valsalva manoeuvre greatly improves
      the echocardiographic detection of PFO with right-to-left shunts in stroke
      patients.

PMID- 7621650
TI  - Lung function in Estonian children: effect of sitting height.
AB  - The present analysis formed part of the population study of Estonian school
      children and was undertaken in order to examine the relationships between lung
      function variables, standing and sitting height. We measured forced vital
      capacity (FVC), forced expiratory volume in 1 s (FEV1), peak expiratory flow and
      forced expiratory flows when 50 and 75% of FVC had been exhaled, and
      anthropometric indices in 645 healthy schoolchildren, aged 6-18 years. The growth
      spurt in standing and sitting height occurred between the ages of 11 and 13 years
      in girls, and 13 and 15 years in boys. Growth spurts of lung parameters occurred
      during the same periods. FVC and FEV1 showed close correlations (r = 0.89-0.94)
      with all anthropometric parameters and age, whereas correlation coefficients for
      the flows were less close (r = 0.65-0.88). In boys, correlations between sitting
      height and lung function variables were greater than those with standing height.
      Using stepwise regression analysis, in boys sitting height was selected in all
      lung function parameters, and in girls sitting height was never selected. We
      conclude that there is a very close correlation between sitting height and lung
      function variables. The use of sitting height in parallel with standing height in
      predicted values for Estonian schoolchildren would make the values more exact.

PMID- 7621649
TI  - Knee extensor performance of dominant and non-dominant limb throughout repeated
      isokinetic contractions, with special reference to peak torque and mean frequency
      of the EMG.
AB  - The aim of this study was to investigate whether significant differences in peak
      torque (PT), mean power frequency of EMG (fmean) and perceived fatigue exist
      between the dominant and non-dominant knee extensors throughout repeated
      contractions. The present study forms part of a research project aimed at
      developing tests for the determination of the degree of motor control in patients
      with sequelae after CNS injury. A total of 22 clinically healthy subjects (14
      males and eight females) took part in the investigation. The subjects performed
      endurance tests of the lower limbs, consisting of 100 repeated knee extensions
      using a Cybex dynamometer at 1.57 rad s-1. The patterns of PT, fmean and
      perception of fatigue throughout the endurance test were investigated. The
      endurance curves of PT and fmean showed, in common with other studies, an initial
      steep decrease followed by a stable phase. No significant differences existed
      between dominant and non-dominant knee extensors with regard to PT, fmean or
      perception of fatigue. The results indicate that it may be possible to use the
      contralateral knee extensors as an indicator of motor recovery in hemiplegia in
      patients with a high degree of recovery.

PMID- 7621652
TI  - Chronic hypertension in pregnancy.

PMID- 7621653
TI  - Pediatric and adolescent gynecology.

PMID- 7621654
TI  - Nonestrogenic therapy for the menopause.

PMID- 7621651
TI  - Update: cancer screening in women.
AB  - Current cancer screening recommendations for women have been reviewed.
      Controversies have been identified. Many additional references are available upon
      request.

PMID- 7621655
TI  - Treatment of superficial bladder cancer.

PMID- 7621656
TI  - Postcesarean endometritis.

PMID- 7621657
TI  - Will the "age of bureaucracy" silence the rights versus needs debate?

PMID- 7621658
TI  - The current status of academic-mental health linkages in Rhode Island.
AB  - The purpose of this study is to describe the current status of academic-public
      mental health linkages in the State of Rhode Island by querying key informants
      concerning their opinions in the following areas: clinical orientation and
      preferred clinical interventions, specific approaches to academic-mental health
      linkages, training and educational opportunities, obstacles to a career working
      with persons who have persistent and severe mental illness, and recommendations
      to improve academic-mental health linkages. Forty-eight of sixty key informants,
      among them academics, mental health administrators, clinical practitioners and
      consumer advocates, responded to the mailed survey. More than half the
      respondents rated affective disorders, schizophrenia and substance abuse to be
      their highest concern as professionals; most subscribed to biological models of
      mental illness as well as a variety of prevailing treatment strategies employed
      in the care of persons with severe mental illness; generally they rated the
      current status of academic-mental health linkages to be low, but recommended a
      range of remedies to improve and increase collaborative efforts.

PMID- 7621659
TI  - Measuring empowerment in client-run self-help agencies.
AB  - "Empowerment" connotes a process of gaining control over one's life and
      influencing the organizational and societal structures in which one lives. This
      study defines and validates three measures: the Personal Empowerment Scale, the
      Organizational Empowerment Scale, and the Extra-Organizational Empowerment Scale.
      Measurement efforts are based on observational work, baseline interviews (N =
      310), and six month follow-ups (N = 241) in four client-run self-help agencies
      (SHAs) for persons with severe mental disabilities. All three study scales
      demonstrated strong internal consistency and stability. They were sensitive to
      user changes over time and have construct validity.

PMID- 7621660
TI  - A randomized evaluation of consumer versus nonconsumer training of state mental
      health service providers.
AB  - Preliminary evidence suggests that mental health consumers can successfully serve
      as peer companions, case management aides, case managers, job coaches, and drop
      in center staff. However, few empirical investigations have addressed the use of
      consumers to train mental health professionals. This project employed a
      randomized design to test the effects of using consumers as trainers for mental
      health service providers. Fifty-seven state mental health professionals
      participated in a two-day training designed to acquaint trainees with the
      attitudes and knowledge necessary for delivering assertive case management
      services. Participants were randomly assigned to one of two conditions: one in
      which they received the second day of training from a consumer and the other
      involving training by a nonconsumer. Analyses revealed that post-training
      attitudes were significantly more positive for those participants trained by the
      consumer. Subjective evaluations also reflected positive reactions to the use of
      consumers as trainers. Implications for further use of mental health consumers as
      trainers are explored.

PMID- 7621661
TI  - Schizophrenia in popular periodicals.
AB  - To examine what the general public is learning about schizophrenia, all articles
      on schizophrenia listed in the Reader's Guide to Periodical Literature for all
      even-numbered years between 1964 and 1992 were read and rated. Hallucinations and
      delusions were the most commonly mentioned symptoms in the articles reviewed,
      biochemical dysfunction and heredity the most noted causes, and drugs the most
      cited treatment. The average yearly number of articles was relatively small,
      however (9.1), and only a minority of those appeared in general circulation
      magazines. In addition, community support was seldom included in discussions of
      treatment and specific misconceptions about schizophrenia were rarely addressed.

PMID- 7621662
TI  - Schizophrenia and the life cycle.
AB  - We reframe the longitudinal treatment of persons with schizophrenia from the
      perspective of phases in adult development. This approach articulates the need
      for different interventions of varying intensities over the person's lifetime.
      The paper discusses the implications of an adult developmental perspective in
      managing pharmacologic treatment and psychosocial interventions, and in
      reallocating financial resources for improved long-term outcomes. This
      perspective is especially useful in the context of a comprehensive community
      mental health program permitting access to a continuum of services throughout the
      lifecycle.

PMID- 7621664
TI  - The role of inpatient care for patients with co-occurring severe mental disorder
      and substance use disorder.

PMID- 7621663
TI  - Substance abuse and the chronically mentally ill: a description of dual diagnosis
      treatment services in a psychiatric hospital.
AB  - Between 20% and 70% of psychiatric patients have a co-occurring substance use
      disorder and rates of substance abuse among patients with psychotic disorders are
      especially high. Patients with co-existing psychosis and substance use disorders
      typically have poorer outcomes than patients diagnosed with either disorder
      alone. Frequently, treatment services for such dually diagnosed patients are not
      integrated and organizational barriers may impede the appropriate detection,
      referral, and treatment of these patients. This article reviews the epidemiology
      and treatment outcome for patients dually diagnosed with chronic mental illness
      (usually psychotic disorders) and substance use disorders. The article then
      presents a description of a dual diagnosis referral and treatment service in a
      large private, non-profit psychiatric hospital.

PMID- 7621665
TI  - Substance abuse and the chronically mentally ill: therapeutic alliance and
      therapeutic limit-setting.

PMID- 7621666
TI  - Seasonal variations in the immune system of the cyprinid Tinca tinca. Phagocytic
      function.
AB  - Seasonal variations in the in vitro phagocytic process of blood granulocytes from
      the tench Tinca tinca were examined. Different stages of the phagocytic process:
      mobility rate, attachment, ingestion and killing of Candida albicans were
      evaluated. Tench were kept in natural ponds in ambient water temperature, and the
      in vitro assays were performed at both 22 degrees C and the relative ambient
      temperature. Results between the seasonal samples were then compared. In vitro
      induced mobility, attachment, ingestion and killing of C. albicans showed strong
      seasonal variations, furthermore, the phagocytic process at 22 degrees C varied
      significantly according to season. Phagocytic activity from samples taken during
      the spring demonstrated the highest activity at 22 degrees C, whilst greatest
      activity at seasonal temperature, in terms of mobility rate, phagocytic index and
      microbicide capacity, occurred during the winter. These results are consistent
      with the hypothesis that phagocytosis in fish is resistant to low temperatures.

PMID- 7621667
TI  - Effect of high summer temperatures upon granulocyte phagocytic function of the
      tench (Tinca tinca, L.).
AB  - Phagocytic activity and NBT reduction by blood granulocytes was evaluated in
      tench during the summer, when water temperature was high (30 degrees C). In vitro
      assays were performed at two temperatures, 30 degrees C, the temperature of the
      natural habitat in summer, and 22 degrees C, a commonly used temperature within
      the optimum range of warm-water fish. The results indicate that blood
      granulocytes from tench possess a lower capacity to ingest inert particles at 30
      degrees C than at 22 degrees C, particularly during long periods of incubation
      (60 min). The lower capacity for ingesting inert particles at 30 degrees C is due
      to a decreased effectiveness of phagocytosis at this temperature, but not to a
      lower number of granulocytes with phagocytic capacity. The decline in inert
      particle ingestion capacity does not correspond to a lower production of
      superoxide anion at 30 degrees C, which is similar at both temperatures during
      phagocytosis, thus indicating a similar capacity for destruction of the antigen
      at 30 and 22 degrees C.

PMID- 7621668
TI  - Intracellular activity of both teicoplanin and vancomycin against Staphylococcus
      aureus in human neutrophils.
AB  - The effects in vitro of both teicoplanin and vancomycin of blood peripheral human
      neutrophils have been studied by assays of antibiotic uptake and intracellular
      killing of previously phagocytosed Staphylococcus aureus. The effects of
      vancomycin and teicoplanin (a novel glycopeptide antibiotic), at the therapeutic
      concentrations reached in plasma (10, 25, 50, 75 and 100 mg/l) and at different
      times of incubation (5, 15, 30 and 60 min) were studied. The results indicate
      that: (1) the bactericidal effect of neutrophils increases with incubation time,
      (2) in the presence of both teicoplanin and vancomycin, the number of CFU/ml of
      intraphagocytic S. aureus declines with both increasing incubation time and
      exposure dose of the antibiotics and (3) at 100 mg/l of teicoplanin there is a
      significant increase in the percentage inhibition of S. aureus growth at all the
      times studied.

PMID- 7621669
TI  - Enhancement of rotavirus infectivity by saturated fatty acids.
AB  - The effect of different saturated fatty acids from 10 to 16 carbon atom chains
      and some derivatives on the infectivity of SA-11 rotavirus was examined. Both
      fatty acids and derivatives induced an increase of rotavirus infected LLC-MK2
      cells when present during viral absorption to host cells. Capric acid and
      palmitic acid were the most effective with a dose-dependent relationship. These
      last lipids, in the same experimental conditions, failed to restore the
      susceptibility to infection of LLC-MK2 cells made resistant by neuraminidase
      treatment or to allow cell infection by non-infectious single-shelled viral
      particles. Results obtained suggest that the enhancing effect on viral
      infectivity by saturated fatty acids requires previous binding of rotaviral outer
      capsid proteins to sialic acid containing cell receptors.

PMID- 7621670
TI  - Patterns of prostaglandin E2 and leukotriene B4 production in inflammation
      induced by peptidoglycan-polysaccharide polymers of bacterial cell walls.
AB  - The changing levels of prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) were
      compared over a period of 1 h to 15 days in two kinds of inflammatory responses
      induced in the rat air pouch by chemically similar polymers of peptidoglycan
      polysaccharide (PG-PS) isolated from cell walls of group A streptococci. The
      smaller polymers (100 s, average mol. wt 5.3 x 10(6)) induced a more severe acute
      response over the first 24 h, whereas, from 3 to 15 days the larger polymers (10
      p, average mol. wt 5 x 10(8)) induced greater chronic inflammation, as measured
      by pouch fluid volume, number of infiltrating cells and weight of granulation
      tissue. The most prominent difference between the two kinds of responses in the
      pattern of PGE2 and LTB4 were: (a) A shift between 1 to 6 h to much higher
      production of PGE2 in the exudate induced by large polymers. During this time the
      level of LTB4 also increased, but continued to be higher in the exudate induced
      by small polymers. (b) The sustained production of relatively high levels of LTB4
      and PGE2 in the large polymer exudate at 15 days. Changes such as these indicate
      that this model is useful for analyzing mediators which regulate the evolution of
      acute into chronic inflammation.

PMID- 7621672
TI  - The use of a non-specific defence mechanism inducer in calves exposed to bovine
      herpesvirus-1 infection: preliminary trials.
AB  - The efficacy of an immunomodulator, the Baypamun (Bayer AG), was tested in calves
      which were subsequently exposed to bovine herpesvirus-1 (BHV-1) infection. Two
      groups of calves, of 8 animals each, were used for two trials. In one trial, 4
      calves were treated with the immunomodulator and the remaining 4 were left as
      untreated controls. Two hours after the first injection of Baypamun, all calves,
      i.e. the treated and the untreated ones, were challenged with BHV-1. Comparing
      them to the untreated controls, the calves which were given the immunomodulator
      developed milder signs of the disease and shed a significantly lower
      concentration of virus. In the second experiment, 4 calves were given Baypamun
      and 4 calves were not, as above, but they were not inoculated with BHV-1;
      however, they were housed together with the calves of the former group
      (experimentally infected with BHV-1). The 8 calves all became infected but those
      that had been treated with Baypamun did not show any clinical signs of the
      disease, whereas the untreated calves underwent a clinical response which was
      considered to be typical of BHV-1 respiratory infection, as usually seen under
      natural conditions. In this case the shedding of virus by the calves treated with
      the immunomodulator also underwent a significant reduction.

PMID- 7621671
TI  - Anisakidosis: report of 25 cases and review of the literature.
AB  - Anisakidosis (previously known as anisakiasis) is a disease caused by the
      accidental ingestion of larval nematodes (Anisakis and sometimes Pseudoterranova)
      in raw fish. Two groups of patients are studied: 5 clinical cases and 20
      serological diagnoses. 55 French cases are already published. Most of them
      complained of acute symptoms, which occurred within 12 h of eating the seafood
      meal--epigastric pain, occlusion, diffuse abdominal pain, and appendicitis.
      Larvae were attached to the gastric mucosa (25 cases), including an inflammatory
      response (erythema, oedema ulceration). Diagnosis of anisakiasis is made by
      gastroscopy which allows removal of the worms, and cures the patients. In gastro
      intestinal tract X-rays, oedema in the mucosa, pseudo tumour formation, and
      filling defects (worm) were observed. In chronic infections, cases with
      intermittent feelings of ill health and abdominal pain, lasting from several
      weeks to months, were misdiagnosed as another intestinal disease. Positive
      serological reactions are helpful, and surgery is necessary for resection of the
      lesion; diagnosis is made histologically by an eosinophilic granuloma, and the
      presence of a larva with Y shaped lateral cords. Infestation rate is high in
      fishes: cod (88%), rock fish (86%), herring (88%), salmon, mackerel. Public
      health education should discourage the eating of raw fish. Thorough cooking to 70
      degrees C or adequate freezing to -20 degrees C for 72 h are the best preventive
      measures. Such legislation is only in force in the Netherlands, where cases have
      decreased dramatically.

PMID- 7621673
TI  - Prevalence of group A and group B rotaviruses in the feces of neonatal dairy
      calves from California.
AB  - 136 fecal samples, collected from 47 dairy calves on a calf ranch and in a dairy
      herd in California, were tested for the presence of group A and group B
      rotaviruses by reverse transcription-polymerase chain reaction (RT-PCR). Samples
      were collected from each calf at days 1, 7 and 14. Within the 14 day period, 44
      calves (94%) were positive for group A rotavirus and an unexpectedly high number
      of calves (38 calves, 81%) were positive for group B rotavirus. When these
      samples were examined by polyacrylamide gel electrophoresis (PAGE), rotavirus was
      found in 21 calves and all of them had group A electropherotype. Among 25 PAGE
      positive samples from 21 calves, 17 (68%) were of short electropherotype, 4 (28%)
      were of long electropherotype and 4 (28%) contained both short and long
      electropherotype rotaviruses. Group B and short and long electropherotype group A
      rotaviruses were found in both normal and diarrheic calves.

PMID- 7621675
TI  - Effect of somatotropin on adipose tissue metabolism: ontogeny of the enhanced
      response to adrenergic challenge in the lactating cow.
AB  - Seven multiparous Holstein cows (> 150 d postpartum) were used to evaluate the
      time course of the chronic adaptation in lipolytic response to adrenergic
      challenge with bovine somatotropin (bST) treatment. Cows received daily bST
      (sometribove; 40 mg/d) or excipient injections for 7 d (single reversal design)
      with a 7-d interim between periods. Epinephrine challenges (1.4 microgram/kg body
      weight intravenously) were administered on Days -2, -1, 1, 2, 3, 5, and 7 of
      treatment at 10:00 a.m. (15 hr after bST or excipient injection). Frequent blood
      samples were collected, and concentrations of plasma glycerol (GLY) and
      nonesterified fatty acids (NEFA) were determined. Treatment with bST increased
      milk yield 23% (P < 0.05) and milk fat content 33% (P < 0.001) compared with
      controls. Somatotropin-treated cows entered negative energy balance by Day 3 and
      had higher basal plasma concentrations of GLY and NEFA than did controls by Day 2
      and Day 3, respectively. Response to epinephrine, expressed as area under the
      response curve corrected for basal, was enhanced by bST treatment, regardless of
      energy balance. GLY response was greater than control by Day 1 of bST treatment
      (P < 0.01), and had plateaued by Day 2 (P < 0.001). The NEFA response area was
      higher than control and had plateaued by Day 1 of bST treatment (P < 0.001). Day
      1 represented 15 hr after the first bST injection. Results illustrate that bST
      treatment results in enhanced in vivo lipolytic response to catecholamine
      challenge, and the metabolic adaptation is in place by 15 hr after the first bST
      injection.

PMID- 7621674
TI  - Concentration of chicken gonadotropin-releasing hormones I and II in
      microdissected areas of turkey hen brain during the reproductive cycle.
AB  - Chicken gonadotropin-releasing hormones I and II (cGnRH I and II) were measured
      by radioimmunoassay (RIA) in extracts of microdissected regions of turkey hen
      brain (preoptic area [POA], region of periventricular nuclei [PHN], septum [SEP],
      hippocampus [HP], dorsomedial thalamus/habenula [DMT], midbrain central gray
      [MCG], and caudal lateral hypothalamus [LH]) at five stages of the reproductive
      cycle: before photostimulation, during egg laying, during incubation, during
      photorefractoriness, and after return to short daylengths. The highest
      concentration of cGnRH I occurred in PHN, followed by POA, SEP, DMT, HP, LH, and
      MCG, in decreasing order, whereas the highest concentration of cGnRH II occurred
      in SEP, followed by POA, DMT, HP, MCG, PHN, LH. These results agree, with some
      exceptions, with the distribution of fibers and cells as determined by
      immunohistochemistry. cGnRH II was from 1.3 to 24 times as abundant as cGnRH I in
      different brain areas. During incubation, cGnRH I concentrations were
      significantly elevated in the POA and cGnRH II levels were significantly elevated
      in HP; few other significant differences were detected. Correlation analysis
      detected occasional significant positive and negative correlations between cGnRH
      I and II concentrations in forebrain areas and MCG of laying birds and in PHN and
      LH of incubating birds. These results demonstrate an approximate correspondence
      between hormone concentrations measured in tissue extracts by RIA and
      immunohistochemistry and indicate an abundance of cGnRH II as compared with cGnRH
      I. cGnRH I and II concentrations did not, however, change in parallel in all
      brain areas, suggesting that these peptides do not function in an exactly
      parallel fashion. Thus, an extent to which cGnRH II is involved in gonadotropin
      release remains unresolved.

PMID- 7621676
TI  - Chronic glucocorticoid excess and impaired osmoregulation of vasopressin release
      in dogs with hepatic encephalopathy.
AB  - Chronic liver disease may be accompanied by disturbed sodium and water
      homeostasis. There is usually sodium retention and ascites. However, spontaneous
      natriuresis has also been reported in humans and experimental animals with liver
      cirrhosis. Chronic hypercortisolism, which may occur in dogs with advanced liver
      disease, is known to induce the inhibition of the osmostimulation of vasopressin
      (AVP) release. We have therefore investigated the osmoregulation of AVP release
      in 11 dogs with chronic hypercortisolism associated with advanced liver
      dysfunction and hepatic encepahlopathy and in 10 control dogs. Basal pituitary
      adrenocortical activity was investigated by measuring the concentration in
      multiple plasma samples of adrenocorticotropin (ACTH), alpha-melanocyte
      stimulating hormone (MSH), and cortisol and the cortisol:creatinine ratio in 24
      hr urine. Urine specific gravity was also measured. The feedback regulation of
      the system was investigated by measuring these hormones in plasma after an
      intravenous (iv) injection of 0.01 mg/kg of dexamethasone. The osmoregulation of
      the release of AVP was investigated by the intravenous infusion of a 20% NaCl
      solution at a flow rate of 0.03 ml/kg for 2 hr and the measurement of AVP in
      plasma sampled at 20-min intervals. The AVP release was analyzed in terms of the
      threshold osmolality at which it commenced and the sensitivity, which reflects
      the magnitude of the response. All dogs had highly increased urinary
      cortisol:creatinine ratios, ranging from 21 to 210 x 10(-6) (normally < 10 x 10(
      6)). The mean basal plasma concentrations of the three pituitary-adrenocortical
      hormones were significantly increased. ACTH values were 35 to 146 ng/l (normally,
      14 to 68), MSH values were 26 to 118 ng/l (normally, 10 to 36), and cortisol
      values were 88 to 194 nmol/l (normally, 23 to 112). The feedback inhibition of
      the secretion of ACTH and cortisol in response to dexamethasone was unaffected.
      Urine specific gravity was significantly decreased. The regulation of AVP release
      was found to be abnormal in all dogs with hepatic encephalopathy. The osmotic
      threshold at which the release of AVP was induced was abnormally high in seven of
      the dogs with liver disease and in the normal range in one. It could not be
      determined in three dogs. The sensitivity of AVP release in response to
      increasing plasma hypertonicity was normal in two dogs and decreased in nine. In
      three dogs, there was no increase in AVP release. None of the dogs had normal
      values for both the sensitivity and the threshold.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 7621677
TI  - Contact-associated interactions between large and small bovine luteal cells
      during the estrous cycle.
AB  - This experiment was designed to study the effects of cell-to-cell contact,
      arachidonic acid (10 microM; AA), oxytocin (10 microM), and luteinizing hormone
      (5 ng; LH) on bovine luteal cell function. Corpora lutea collected from Holstein
      cows between Days 10 and 12 (n = 4; midluteal stage) or 17 and 18 (n = 4; late
      luteal stage) of the estrous cycle (Day 0 = estrus) were dispersed, and small and
      large cells were separated by unit gravity sedimentation and flow cytometry.
      Large and small luteal cells were either incubated together, allowing
      intercellular contact, or separately, without intercellular contact, with culture
      well inserts. Cells were incubated in a modified Ham's F-12-N
      hydroxyethylpiperazine-N'-2-ethanesulfonic acid medium. After an 18-hr
      preincubation period, treatments were introduced and cells were incubated for 240
      hr. Media samples were collected and treatments were replaced at 48-hr intervals.
      Incubations were maintained at 37 degrees C in 5% CO2 in humidified air. Overall,
      progesterone secretion decreased with increased incubation time (P < 0.0001),
      regardless of treatment, stage of the cycle, or cell arrangement. During the 18
      hr pretreatment period, large and small luteal cells with contact secreted more
      progesterone than did luteal cells without contact during both the mid- (P <
      0.0001) and late-luteal stages (P < 0.06) of the estrous cycle. After treatments
      were initiated, both mid- and late-stage luteal cells treated with LH secreted
      more (P < 0.0001) progesterone than occurred with any other treatment; oxytocin,
      AA, and control treatments were similar.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7621678
TI  - Laboratory diagnosis of equine pituitary pars intermedia adenoma.
AB  - The objective of the study was to determine the sensitivity with which an adenoma
      of the pars intermedia of the pituitary gland can be predicted in horses by
      measuring the basal concentrations of glucose, cortisol, adrenocorticotropin
      (ACTH), and insulin, the urinary concentration of corticoids, the urinary
      corticoid:creatinine ratio, and the plasma cortisol concentration after the
      administration of 25 IU of ACTH intravenously. The records of 24 cases of
      histologically confirmed equine pituitary pars intermedia adenomas were used. An
      adenoma of the pars intermedia of the pituitary gland in horses was predicted
      with a sensitivity of 100, 100, and 92% for basal plasma ACTH (n = 16), the
      urinary corticoid:creatinine ratio (n = 7), and basal plasma insulin (n = 12),
      respectively. The sensitivity of the ACTH-stimulation test was 79% (n = 14).

PMID- 7621679
TI  - Evaluation of biochemical and structural changes in individual porcine corpora
      lutea during prostaglandin F2 alpha-induced luteolysis with an in vivo implant
      system.
AB  - To date, no in vitro system has been devised to allow the study of both the
      functional and the structural regression of luteal cells in response to
      prostaglandin (PG) F2 alpha. This study describes the use of a novel intraluteal
      PGF2 alpha implant system that results in the death of individual corpora lutea
      (CL), while surrounding CL on the same ovary remain fully functional. By this
      technique, it was possible to study both the functional and the structural
      regression of individual CL in vivo, without the confounding effects resulting
      from the systemic injection of PGF2 alpha. Biochemical measurements of individual
      CL included progesterone concentration, protein kinase C activity, and
      diacylglycerol levels. Structural measurements included luteal weight and the
      protein:DNA ratio, which was used to estimate cell size. Further, the
      determination of large luteal cell size was accomplished directly via light
      microscopy. Nonpregnant gilts were injected with 5 mg of estradiol benzoate every
      12 hr from 8:00 a.m. on Day 11 to 8:00 a.m. on Day 13 to prevent uterine PGF2
      alpha secretion. At 7:00 a.m. on Day 13, CL on one ovary were selected at random
      to receive PGF2 alpha-implants (n = 4) or implant material only (n = 4), whereas
      the remaining CL on that ovary served as unimplanted controls. The other ovary
      was removed at the point, and the CL on that ovary served as 0-hr controls. Gilts
      were relaparotomized at 3, 6, 12, and 24 hr after CL implantation, the PGF2 alpha
      implanted ovary was removed, and individual CL were evaluated. PGF2 alpha
      implanted CL exhibited a decline (P < 0.05) in progesterone concentrations at 12
      and 24 hr and a decline (P < 0.05) in weight at 24 hr when compared with control
      CL (implant-only, unimplanted, and 0-hr control CL). Furthermore, the protein:DNA
      ratio was reduced (P < 0.10) in the PGF2 alpha-treated CL at 12 and 24 hr.
      Moreover, this change in the protein:DNA ratio (cell size) was consistent with
      the reduced diameter (P < 0.05) of the large luteal cell in the PGF2 alpha
      treated CL. Protein kinase C activity and diacylglycerol concentrations did not
      change (P > 0.10) and therefore appear to be unassociated with either functional
      or structural changes in the PGF2 alpha-treated CL. Contrary to in vitro culture
      studies, the results of our in vivo study demonstrate no clear role for protein
      kinase C in the PGF2 alpha-induced luteolytic process.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 7621680
TI  - Effect of uterine space and fetal sex on conceptus development and in vitro
      release of progesterone and estrone from regions of the porcine placenta
      throughout gestation.
AB  - Intact (n = 17) and unilaterally hysterectomized-ovariectomized (UHOX, n = 19)
      gilts were used to study conceptus development and the steroidogenic capability
      of three regions of the porcine placenta under normal and crowded intrauterine
      conditions. Gilts were hysterectomized on either Days 30, 50, 70, or 90 of
      gestation. Placentas were combined according to the sex of the fetus associated
      with the placental unit, except at Day 30, when all were combined. Placentas were
      cut into three regions: middle, inner, and polar. Placental tissues were
      incubated for 0, 1, 5, and 3 hr, and concentrations of progesterone (P4) and
      estrone (E1) in the incubation medium were determined. Fetal survival rate was
      greater (P < 0.01, 0.05, and 0.001 at days 50, 70, and 90, respectively) in
      intact than in UHOX gilts. Placental length and weight, fetal length and weight,
      and allantoic fluid volume were greater (P < 0.05, 0.001, 0.05, and 0.001,
      respectively) in intact than in UHOX gilts. P4 concentration was lower (P <
      0.001, 0.002, and 0.001 at Days 50, 70, and 90, respectively) in the incubation
      medium of polar region placenta compared with the other regions. The release of
      P4 was greater (P < 0.005) from the placentas of intact versus UHOX gilts at Day
      90 but was not different at Days 30, 50, or 70. The sex of the fetus did not
      affect placental P4 release. The region of the placenta affected E1 release at
      Day 30 (P < 0.01, greater in polar section) and Day 50 (P < 0.06, less in polar
      section). There was no effect of uterine status on E1 release.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7621681
TI  - Maternal treatment with somatotropin alters embryonic development and early
      postnatal growth of pigs.
AB  - A possible management strategy to alter fetal development and enhance sow
      productivity and progeny performance was examined by maternal administration of
      porcine somatotropin during early gestation. Eighteen crossbred gilts were bred
      naturally to boars of similar genetics, and pregnancy was confirmed between Days
      21 and 24 of gestation by ultrasound. All animals were allowed ad libitum
      consumption of a 16% CP gestation diet through Day 21 of gestation and 3.0 kg/d
      for the remainder of gestation. Gilts were injected twice daily with 0 (n = 10)
      or 15 micrograms/kg body weight (BW) (n = 10; total, 30 micrograms/kg BW per d)
      pituitary-derived porcine somatotropin (pST) during Days 28 to 40 of gestation.
      Data were collected postmortem during embryonic, neonatal, and market-weight
      phases. At 41 d of gestation, pST treatment increased embryonic survival (87.9
      versus 77.0%; P < 0.05) and embryo crown rump lengths (77.96 versus 65.14 mm; P <
      0.01), but embryo weight was not altered (10.15 and 9.03 g; P > 0.10). Pigs from
      pST-treated gilts had increased (P < 0.01) crown rump lengths at birth (31.5
      versus 30.4 cm) and 21 d (50.9 versus 48.4 cm). However, no differences were
      observed in birth or 21-d weights as a result of pST treatment (P > 0.10).
      Neonatal carcasses of progeny (20 kg BW) from the pST-treated gilts had heavier
      semitendinosus muscles (76.1 versus 66.0 g; P < 0.10), larger longissimus muscle
      cross-sectional area (10.1 versus 8.2 cm2; P < 0.05), longer sides (51.2 versus
      47.9 cm; P < 0.001), and decreased 10th rib backfat (6.67 versus 8.64 mm; P <
      0.001) compared with those of controls. Carcasses of market-weight progeny (100
      kg BW) from pST-treated gilts had larger longissimus muscle cross-sectional area
      (P < 0.10), heavier trimmed loins (P < 0.10), and longer carcass sides (P <
      0.05). Data are supportive of a hypothesis that mechanisms during early embryonic
      development are sensitive to manipulation through selected management strategies
      of the sow and that modifications of this strategy may serve as a model for the
      examination of molecular and cellular events controlling early embryonic growth.

PMID- 7621682
TI  - Relationship between phosphoinositide hydrolysis and prostaglandin F2 alpha
      secretion in vitro from endometrium of cyclic pigs on day 15 postestrus.
AB  - The mechanism for the luteolytic release of prostaglandin (PG)F2 alpha in swine
      is not known. This study examined the potential role of oxytocin (OT)-induced
      phosphoinositide (PI) hydrolysis in promoting PGF2 alpha secretion in vitro from
      the endometrium of cyclic gilts on Day 15 postestrus. In Experiment 1,
      endometrial PI hydrolysis was increased (P < 0.05) by 100 nM OT and was increased
      quadratically (P < 0.05) by LiCl, but was not affected by the LiCl x OT
      interaction (P > 0.30). PI hydrolysis was maximal at 50 mM LiCl and declined at
      100 mM LiCl. In Experiment 2, endometrial PI hydrolysis and PGF2 alpha secretion
      were similarly increased (P < 0.01) by 0, 0.1, 1, 10, and 100 nM OT in a dose
      dependent manner. In Experiment 3, the linear increase in PI hydrolysis occurring
      0, 3, 5, 10, and 20 min after treatment was greater (P = 0.01) for tissue treated
      with 100 nM OT than for the tissue treated with 0 nM OT. The quadratic increase
      (P < 0.05) in PGF2 alpha secretion occurring 0, 3, 5, 10, and 20 min after
      treatment was greater (P < 0.05) for tissue treated with 100 nM OT than for the
      tissue treated with 0 nM OT. In Experiment 4, AlF4- (an activator of Gp and
      phospholipase C) similarly increased (P < 0.01) PI hydrolysis and PGF2 alpha
      secretion. In Experiment 5, PI hydrolysis (P < 0.01) and PGF2 alpha secretion (P
      < 0.05) were increased by 100 nM OT but were not stimulated by cholera toxin (an
      activator of Gs and adenylate cyclase). Cholera toxin also did not enhance PI
      hydrolysis and PGF2 alpha secretion in response to 0.1 or 100 nM OT. These
      results are consistent with the hypothesis that OT may induce PI hydrolysis to
      stimulate the endometrial secretion of PGF2 alpha during corpus luteum regression
      in swine.

PMID- 7621683
TI  - Metabolic parameter, bleeding, and weight changes in U.S. women using progestin
      only contraceptives.
AB  - Our objective was to determine the effect of progestin-only contraceptives on
      metabolic parameters, bleeding patterns, and weight changes during the first year
      of use. Seventy-one women (> 95% Caucasian), who were advised regarding
      contraception alternatives, self-selected levonorgestrel implants (n = 44), depo
      medroxyprogesterone acetate (n = 22), or oral norethindrone (n = 5). One year
      later, 11 levonorgestrel implant and five depomedroxyprogesterone acetate
      patients were randomly selected to compare (pre- and post-progestin use) levels
      of cholesterol, triglycerides, low density lipoprotein (LDL), high density
      lipoprotein (HDL), very low density lipoprotein (VLDL), apolipoproteins A-1 and B
      100, bilirubin, and sex hormone binding globulin. Monthly bleeding and spotting
      records were kept in each group. Body weights were also monitored in each group.
      No statistically significant differences in metabolic parameters were found
      between pre- and post-progestin use in the levonorgestrel implant and depo
      medroxyprogesterone acetate groups. Continued bleeding patterns were more
      prominent in the levonorgestrel implant and oral norethindrone groups than in
      patients receiving depo-medroxyprogesterone acetate. No significant weight gain
      was detected in any group. No changes in metabolic parameters or weight were
      noted over the one year of use of levonorgestrel implants or depo
      medroxyprogesterone acetate. Depo-medroxyprogesterone acetate had the highest
      incidence of amenorrhea.

PMID- 7621684
TI  - Vaginal bleeding patterns of women using different contraceptive methods
      (implants, injectables, IUDs, oral pills)--an Indian experience. An ICMR Task
      Force Study. Indian Council of Medical Research.
AB  - Irregularity in vaginal bleeding patterns is the most common clinical side effect
      causing discontinuation of the method reported by the-users of the newer
      contraceptive methods, especially hormonal ones. An objective assessment of
      vaginal bleeding pattern is, therefore, critical in evaluation of a new
      contraceptive method for its acceptance and continued use. The menstrual diary
      records of women participating in clinical trials of several contraceptive
      methods undertaken by the Indian Council of Medical Research were analysed. It
      was observed that the long-acting progestogen-only hormonal contraceptives like
      levonorgestrel (LNG)-releasing subdermal implants Norplant or intrauterine
      devices (LNG-IUD) as well as injectable contraceptive NET-EN 200mg given 2 or 3
      monthly produced disturbances in bleeding pattern in the majority of their users.
      Very heavy or prolonged bleeding, a potential health hazard was uncommon and a
      shift more towards infrequent bleeding was observed. In Norplant-II implants
      users, 75 to 80% of women had irregularities in bleeding pattern during the first
      year of use which improved with prolonged use. However, even at 4 years of use,
      about half of the users of Norplant-II implants continued to have irregular
      bleeding patterns. The bleeding disturbances occurred in 80% users of 200mg NET
      EN injectable contraceptives also during first year of use, however unlike
      Norplant-II implants users, there was no improvement with prolonged use. Combined
      monthly injectable contraceptives containing 50mg NET-EN and 5mg estradiol
      valerate caused less bleeding problems with half of the users experiencing normal
      pattern during one year of its use. Combined low-dose oral pills, both triphasic
      and monophasic, produced much better cycle control as compared to any of the
      other hormonal contraceptive-treated groups; about 90% of combined oral pill
      users had normal bleeding patterns during one year of method use. The use of
      copper IUDs was associated with increased bleeding in 18 to 20% of women during
      the initial period of three months which improved with prolonged use. It was
      observed that the women having frequent or prolonged bleeding had discontinued
      the contraceptive method more often as compared to those having delayed bleeding
      episodes or oligomenorrhoea. However, discontinuation rates due to bleeding
      irregularities at one year were lower in Norplant-II implants users as compared
      to other long acting hormonal contraceptive methods such as injectables or IUDs
      in spite of similar or better bleeding patterns in women using these
      methods.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7621687
TI  - Is time-interval between mini-pill ingestion and breastfeeding essential?
AB  - A study was conducted on four alternate days over an eight-day period in a group
      of 12 healthy, 20-35 year old exclusively breast feeding women who were
      interested in weaning their infants. On each study day the women ingested 150
      micrograms levonorgestrel. Maternal blood and milk samples were collected at 2,
      4, 6, and 8 hr intervals after LNG ingestion on the 1st, 3rd, 5th, and 8th day. A
      time-dependent decrease in maternal serum and increase in breast milk levels of
      LNG were observed. Maintaining a time interval between mini-pill intake and
      breastfeeding results in higher levels of LNG in breast milk, thereby exposing
      the infant to a bolus of LNG in a "single-delayed" feed.

PMID- 7621685
TI  - A multicentred phase III comparative clinical trial of Mesigyna, Cyclofem and
      Injectable No. 1 given monthly by intramuscular injection to Chinese women. I.
      Contraceptive efficacy and sid effects.
AB  - A phase III clinical study was carried out among 5680 fertile Chinese women to
      evaluate efficacy and side effects of three monthly injectable contraceptives:
      Mesigyna, Cyclofem and Chinese Injectable No. 1. When used in a once-a-month
      treatment schedule (part 1 of study), the effectiveness of Chinese Injectable No.
      1 was unacceptably low; 36 pregnancies occurred during the first 1743 women
      months of use, 16 before the second injection. The study was restarted with a
      revised injection schedule for Injectable No. 1: two injections separated by 9 +/
      1 days during the first month and subsequent injections given 10-12 days after
      the onset of bleeding, or if no bleeding occurred, 28 days after previous
      injection. In part 2 of the study, 988, 990 and 992 subjects were provided
      Mesigyna, Cyclofem and Injectable No. 1, respectively. Life-table pregnancy rates
      at one year were 0.41%, 0% and 0.77% (p < 0.05), respectively; the overall
      discontinuation rates at one year were 13.9%, 19.1% and 20.4% (p < 0.001).
      Discontinuation rates for bleeding problems were significantly different between
      the groups: discontinuation rates for amenorrhea were 0.58%, 3.71% and 0.68% (p <
      0.001) for Mesigyna, Cyclofem and Injectable No. 1; for other bleeding problems,
      the rates were 4.88%, 8.38% and 12.64% (p < 0.001). There were no significant
      differences between the groups regarding discontinuation for other medical or non
      medical reasons. Mean weight changes after one year of use were small: 0.73, 0.86
      and 0.17 kg for the three groups, respectively. Both Mesigyna and Cyclofem were
      very effective for contraception, but Mesigyna appeared to be tolerated slightly
      better with regard to cycle control; the modified dose regimen for Injectable No.
      1 also gave a low pregnancy rate but was associated with higher rates of
      discontinuation.

PMID- 7621686
TI  - A multicentred phase III comparative clinical trial of Mesigyna, Cyclofem and
      Injectable No. 1 given by intramuscular injection to Chinese women. II. The
      comparison of bleeding patterns.
AB  - Between 1988 and 1992, a randomized phase III clinical trial was conducted in
      China to compare three monthly injectable contraceptives: Mesigyna, Cyclofem and
      Injectable No. 1. This paper presents a detailed analysis of the menstrual
      diaries provided by 5098 (89%) of the subjects. In total, 902, 903 and 913
      diaries were analyzed to compare bleeding patterns induced by Mesigyna, Cyclofem
      and Injectable No. 1. The first withdrawal bleeding usually occurs 14-20 days
      after the first injection for all three of these preparations. Thereafter, 50% of
      Mesigyna users had precisely 3 bleeding/spotting episodes every 90 days, 50% of
      Cyclofem users had 2-3 and 50% of Injectable No. 1 users had 3-4 episodes every
      90 days. Relative to users of Mesigyna or Cyclofem, Injectable No. 1 users had 2
      3 more bleeding/spotting days, and a shorter length of bleeding/spotting-free
      intervals in each period. 63.7%, 41.4% and 60.6% of subjects using Mesigyna,
      Cyclofem and Injectable No. 1, respectively, had bleeding patterns similar to
      their untreated patterns in the first 90-day period. The percentages increased to
      82.2% 67.8% and 75.0% in the fourth 90-day period. A total of 1815 diaries for
      Mesigyna and 1802 for Cyclofem were analyzed for more in depth comparison of
      these two methods. The number of bleeding/spotting days over four periods showed
      little difference between the two group, but there were more spotting days and
      there was greater individual variability among Cyclofem users.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7621689
TI  - Effects of storage and temperature upon soft jelly capsules containing nonoxynol
      as spermicide.
AB  - Recently, adverse effects of long periods of storage and high temperature on
      physical characteristics of the soft jelly capsule wall were observed. In the
      present study, the effects of both parameters upon the mean rupture time of the
      capsule, and the release of the active compound were evaluated in vivo in 40
      women. The results disclosed that the storage for long time and the exposure of
      the capsules to high temperatures, delays significantly the mean rupture time and
      the release of the active compound. A rapid distribution, adequate storage, as
      well as a delay of intercourse after vaginal insertion of the device are
      suggested.

PMID- 7621688
TI  - Insulin sensitivity is unaltered by the use of the Norplant subdermal implant
      contraceptive.
AB  - Prior evaluations of carbohydrate metabolism in Norplant implant users, using the
      oral glucose tolerance test, have shown mild but clinically insignificant
      deterioration of insulin sensitivity. Using the more sensitive insulin tolerance
      test, the effects of the Norplant implant system on insulin sensitivity was
      studied in normal women. Insulin tolerance tests were performed before Norplant
      implant insertion in ten ovulatory female volunteers and repeated after 12 weeks
      of use. Both fasting glucose and fasting insulin values were similar before and
      after the use of Norplant implants. There was no significant difference in either
      the Kitt glucose value or the Kitt insulin value at baseline and at 3 months of
      use. Furthermore, the insulin-to-glucose ratio did not differ before and after
      the use of Norplant implants. There was a significant correlation with BMI and
      Kitt glucose value (r = -0.45, p < .05), as well as between fasting insulin and
      BMI (r = 0.6, p = 0.006). In the first three months of use, the levonorgestrel
      containing implant system, Norplant, does not affect sensitivity to insulin or
      glucose in normal, nondiabetic women.

PMID- 7621690
TI  - Mode of long-term antifertility effect of intrauterine neem treatment (IUNT).
AB  - The mode of antifertility action of intrauterine neem treatment (IUNT) was
      studied. The effect of IUNT on ovarian functions and uterine responsiveness to
      ovarian hormones was examined in adult Wistar rats. The treated animals had
      normal reproductive cycles as indicated by the vaginal smears; serum progesterone
      levels were also in the normal range. Effect of exogenous estradiol following
      IUNT in ovariectomized rats showed comparable uterine weight gain as in control
      group; decidual cell reaction of the uterine epithelium following IUNT was also
      similar to that of control, indicating normal uterine responsiveness to ovarian
      hormones. Unilateral IUNT followed by mating resulted in degeneration of embryos
      on the treated side as noted between days 3-5 post coitum; normal embryos were
      seen on the contralateral side given peanut oil. The study shows that the mode of
      antifertility action of IUNT is not because of uterine unresponsiveness to the
      ovarian hormones but is due to impairment of embryo development. The results of
      this study thus confirm our earlier observations and show further that the
      antifertility effect of IUNT is at the pre-implantation stage, localized and
      without any adverse or toxic effect on the fetal development in the contralateral
      uterine horn of the unilaterally treated rats. The exact mechanism(s) of
      antifertility action of IUNT is being investigated.

PMID- 7621691
TI  - Effects of levonorgestrel on capacity of mouse oocytes for fertilization and
      development.
AB  - This study utilized a mouse model to examine whether levonorgestrel implants,
      such as Norplant, may exert their contraceptive effects in part by adversely
      affecting oocyte quality. Time-release pellets and silastic capsules containing
      levonorgestrel were implanted subdermally in mice and left in situ for periods of
      two or three months. After that time, mice were given injections of gonadotropins
      to stimulate ovulation and oocytes were obtained from the oviducts of the
      animals, inseminated, and subsequently cultured for 96 hrs, some in medium
      supplemented with levonorgestrel. The numbers of oocytes that were fertilized and
      the numbers that developed at least to the morula stage were determined.
      Levonorgestrel was not found to have an adverse effect on either fertilization or
      preimplantation development but instead was found in some cases to increase the
      proportion of oocytes fertilized and the proportion of embryos that developed to
      morulae. Results indicate that the contraceptive effect of levonorgestrel
      implants should be attributed to effects other than diminished oocyte quality and
      they further substantiate the safety of levonorgestrel, suggesting that it will
      not adversely affect early embryonic development in the event that a pregnancy
      should be initiated during its use.

PMID- 7621692
TI  - The anti-progestin CDB 2914 has no antifertility effect in male rats.
AB  - This study examines the effect of an anti-progestin (CDB 2914) with
      antiprogestational potencies similar to RU 486 on spermatogenesis, sperm
      maturation, and fertility in male rats. Adult male rats of proven fertility were
      administered the anti-progestin (10 mg/kg/day) or vehicle (control group) for 14,
      35, and 70 days to study the possible effect of this compound on epididymal sperm
      maturation, post-meiotic sperm development, spermatogenesis, and fertility,
      respectively. Fertility rates of the rats were determined by mating studies. The
      anti-progestin, CDB 2914, had no effect on testis or accessory organ weights,
      epididymal sperm content or motility, testicular sperm count, spermatogenesis,
      and fertility of male rats. This study suggests that anti-progestins, when
      administered even at higher doses than those used in humans, have no
      contraceptive effect in adult male rats.

PMID- 7621693
TI  - Rationale for cholesterol-lowering strategies.

PMID- 7621694
TI  - Infant attachment in a sample adolescent mothers.
AB  - Thirty-eight, healthy, full-term, first-born infants of adolescent mothers were
      assessed in a standardized laboratory setting using a modified Ainsworth Strange
      Situation procedure for assessing attachment. The security rate within this
      sample was 23.7% which differed considerably from that reported in most white
      middle class samples of approximately 55-65%. Within this sample, 31.6% were
      classified as insecure/disorganized which contrasts with 12% in middle class
      white samples reported by Main & Weston. A racial difference was evident. Fewer
      black infants were securely attached than were white. This paper presents the
      findings according to race, sex and age and discusses the implications.

PMID- 7621695
TI  - Prevalence of pervasive developmental disorder in a sample of psychiatrically
      hospitalized children and adolescents.
AB  - Pervasive developmental disorder (PDD) is underrecognized because of lack of
      awareness of the wide range of severity and differing manifestations of the
      disorder. A survey of psychiatrically hospitalized children and adolescents was
      conducted. 3.2% of the sample of boys was found to have PDD. Underappreciation of
      the presence of PDD characterized the patients. Family members experienced a wide
      array of psychiatric symptoms and showed evidence for the presence of familial
      Tourette syndrome.

PMID- 7621696
TI  - A quantitative and qualitative analysis of suicidal preadolescent children and
      their families.
AB  - This study identified a sample of suicidal preadolescent children who also were
      depressed, aggressive, and socially isolated. The study explored the dimensions
      of cohesion and control associated with the families of these children. Two
      hypotheses were suggested: 1) the families have a deficit in emotional bonding
      and 2) the families have a chaotic disciplinary style. It also seems likely that
      children learn suicidal behavior through observation of others in their family
      and social contexts.

PMID- 7621697
TI  - Perceived family functioning among adolescent psychiatric inpatients: validity of
      the family-of-origin scale.
AB  - The Family-of-Origin Scale (FOS) is a 40 item, ten subscale self-report
      instrument designed to assess perceptions of family health. The scale, based on
      the dimensions of Autonomy and Intimacy, has demonstrated reliability and
      validity with adolescents. The FOS was administered to 100 adolescent psychiatric
      inpatients concurrently with the Brief Symptom Inventory (BSI) to examine the
      scale's discriminant and construct validity. When compared with 100 non-clinical
      adolescents, the psychiatric inpatients perceived their family as less healthy on
      all FOS dimensions. Perceived family health on the FOS was negatively and
      moderately correlated with the BSI dimensions. The findings provide psychometric
      and clinical support for the FOS with adolescents.

PMID- 7621699
TI  - The awareness of chromosomal disarrangements in the evaluation of child
      psychiatry patients.
AB  - This case report reviews genetics consultations on psychiatrically hospitalized
      school-age children. Six of 100 patients were noted to have positive genetic
      findings: four with congenital anomalies and/or biochemical/metabolic
      abnormalities and two with chromosomal abnormalities. Three of these patients are
      used to illustrate the occurrence of genetic abnormalities in psychiatrically
      hospitalized children. The indications for chromosomal analysis are discussed.

PMID- 7621698
TI  - Clinical and preventive issues in child custody disputes.
AB  - Clinical efforts in child custody disputes have emphasized preventive measures
      that address the best interests of the child. Examined herein is the impact of
      separation and divorce on families and preventive oriented efforts in contested
      child custody family mediation models. Also addressed are psychological factors
      in mediation, an identified model of family mediation, and clinical issues in the
      contested child custody arena.

PMID- 7621700
TI  - RNA polymerase II transcription and the functional organization of the mammalian
      cell nucleus.
AB  - The study of RNA pol II-mediated transcription regulation has been dominated by
      molecular biological approaches. Although these methods continue to provide
      important insights, other approaches are required to insure against an
      oversimplified view of gene expression. Improvements in EM methods and the
      development of the confocal light microscope have provided alternative and
      complementary means of investigating gene regulation. Information on the
      "context" in which cis- and trans-acting factors operate can be achieved with
      these techniques. As a result, the spatial compartmentalization of nuclear
      processes involved in transcriptional and post-transcriptional processing has
      received considerable attention.

PMID- 7621703
TI  - A species specific satellite DNA family of Drosophila subsilvestris appearing
      predominantly in B chromosomes.
AB  - This paper describes a species specific satellite DNA family (pSsP216) of
      Drosophila subsilvestris, a palearctic species of the D. obscura group. The
      pSsP216 family consists of tandemly arranged 216 bp repetitive units that are
      predominantly localized on B chromosomes. These chromosomes appear in variable
      numbers in the karyotype of this species. Some pSsP216 repeats can also be
      detected in the centromeric heterochromatin of the acrocentric A chromosomes. Two
      strains, one with and the other without B chromosomes, were investigated for
      sequence variability and for the location of this satellite DNA on the
      chromosomes. Among 16 clones of the 216 bp basic repeat unit an overall
      similarity of about 93% and no strain specific differences were found, indicating
      that the B chromosomes may have derived from the A chromosomes (probably the
      dots) by spontaneous amplification of the pSsP216 satellite DNA family.

PMID- 7621704
TI  - Relationship of nucleolus-associated bodies with the nucleolar organizer tracks
      in plant interphase nuclei (Pisum sativum).
AB  - Nucleolus-associated bodies (NABs) have long been noted in interphase nuclei of a
      wide variety of plant species. We have recently shown that these bodies consist
      largely of snRNPs and that they are located on the nucleolar surface in the
      immediate vicinity of the nucleolar organizer tracks. The present study revealed
      that, following exposure of roots to KCN, an agent that induces nucleolar
      segregation, NABs were intimately associated with intranucleolar chromatin.
      Although immunocytochemical tests with anti-DNA indicated that NABs contained no
      demonstrable amounts of DNA, our observations nevertheless add further support to
      the notion that these bodies are somehow related to the nucleolar chromosomes.

PMID- 7621705
TI  - Meiotic pairing in wheat-rye derivatives detected by genomic in situ
      hybridization and C-banding--A comparative analysis.
AB  - Meiosis of triticalextetraploid rye hybrids (genome constitution ABRRR) was
      analysed by genomic in situ hybridization (GISH) and C-banding. The results
      obtained reveal a considerable difference between these techniques with regard to
      their efficiency in detecting any type of pairing, either homologous or
      homoeologous. Thus the percentage of pollen mother cells containing wheat/rye
      homoeologous associations determined by C-banding and GISH was 2.5 and 9.2,
      respectively. Such a discrepancy can be ascribed to a certain proportion of
      wheat/rye associations not being identified by C-banding. The potential and
      limitations of the two techniques for meiotic analysis are discussed.

PMID- 7621702
TI  - Transcription of heat shock gene loci versus non-heat shock loci in Chironomus
      polytene chromosomes: evidence for heat-induced formation of novel putative
      ribonucleoprotein particles (hsRNPs) in the major heat shock puffs.
AB  - The heat shock response of Chironomus polytene chromosomes was reexamined. The in
      vivo effects of heat shock on chromosomal [3H]uridine labeling, RNA polymerase II
      distribution and ribonucleoprotein (RNP) formation were investigated. One primary
      result is a clarification of the number and location of chromosomal sites
      strongly induced by treatment at 37 degrees C for 60 min. In total, seven major
      heat shock loci were identified by transcription autoradiography in Chironomus
      tentans: I-20A, II-16B, II-10C, II-4B, II-1C, III-12B, and IV-5C. Secondly,
      combining immunofluorescence with transcription autoradiography, I find RNA
      polymerase II occurring after heat shock at multiple chromosomal sites that were
      also active under normal conditions (20 degrees C). Furthermore, the results
      demonstrate conclusively that the presence of RNA polymerase II at heat shock and
      non-heat shock loci is generally correlated with [3H]uridine labeling during heat
      shock. These latter results extend and corroborate previous findings. Thirdly,
      the most striking result of this study was revealed in ultrathin sections of
      puffs by electron microscopy: I discerned a site-specific ultrastructural
      difference in putative RNP particles between heat shock versus non-heat shock
      loci. At least three of the seven induced major heat shock puffs (I-20A, III-12B,
      IV-5C) were observed to contain globular particles that were different, i.e.
      significantly larger, 250-1,000 A in diameter with a prominent 500-750 A class,
      than RNP particles of other loci under non-heat shock conditions. These large
      heat shock puff particles presumably represent nascent or newly synthesized heat
      shock RNA associated with protein(s) to form heat shock RNPs (hsRNPs). This
      finding suggests the possible involvement of novel RNPs (hsRNPs) in
      transcriptional regulation or heat shock RNA turnover and may stimulate further
      molecular investigations on this subject in both cell physiological and
      structural terms. I conclude that the locus-specific putative hsRNPs are an
      intrinsic property of greatly increased heat shock gene transcription.

PMID- 7621701
TI  - Changes in the subcellular localization of replication initiation proteins and
      cell cycle proteins during G1- to S-phase transition in mammalian cells.
AB  - DNA replication in eukaryotic cells is restricted to the S-phase of the cell
      cycle. In a cell-free replication model system, using SV40 origin-containing DNA,
      extracts from G1 cells are inefficient in supporting DNA replication. We have
      undertaken a detailed analysis of the subcellular localization of replication
      proteins and cell cycle regulators to determine when these proteins are present
      in the nucleus and therefore available for DNA replication. Cyclin A and cdk2
      have been implicated in regulating DNA replication, and may be responsible for
      activating components of the DNA replication initiation complex on entry into S
      phase. G1 cell extracts used for in vitro replication contain the replication
      proteins RPA (the eukaryotic single-stranded DNA binding protein) and DNA
      polymerase alpha as well as cdk2, but lack cyclin A. On localizing these
      components in G1 cells we find that both RPA and DNA polymerase alpha are present
      as nuclear proteins, while cdk2 is primarily cytoplasmic and there is no
      detectable cyclin A. An apparent change in the distribution of these proteins
      occurs as the cell enters S-phase. Cyclin A becomes abundant and both cyclin A
      and cdk2 become localized to the nucleus in S-phase. In contrast, the RPA-34 and
      RPA-70 subunits of RPA, which are already nuclear, undergo a transition from the
      uniform nuclear distribution observed during G1, and now display a distinct
      punctate nuclear pattern. The initiation of DNA replication therefore most likely
      occurs by modification and activation of these replication initiation proteins
      rather than by their recruitment to the nuclear compartment.

PMID- 7621706
TI  - A tightly bound chromosome antigen is detected by monoclonal antibodies in a ring
      like structure on human centromeres.
AB  - Monoclonal antibodies (Mabs) were raised against isolated Chinese hamster protein
      depleted chromosomes Chromosome scaffolds) in order to probe for components
      involved in the higher-order structure of mammalian chromosomes. One of the Mabs
      detected a ring-like structure in metaphase at the centromere, which is conserved
      between Chinese hamster and human cells. Additionally, the Mab stained the
      centrioles in interphase cells in these two species. The antigen was enriched in
      chromosomal protein preparations by comparison with nuclear protein samples, and
      has an apparent Mr = 170,000. The centromere antigen remained present in
      chromosome scaffold preparations, indicating that it was tightly associated with
      DNA. The antigen was distinct in its centromeric localisation from any of the
      centromere antigens reported to date. A possible role of the antigen in
      stabilising the centromere, by holding the sister chromatids together until their
      separation at the metaphase-anaphase transition is presented.

PMID- 7621707
TI  - The late replication banding patterns of chromosomes are highly conserved in the
      genera Rana, Hyla, and Bufo (Amphibia: Anura).
AB  - Late replication banding and C-banding analyses were performed on the metaphase
      chromosomes of six species and one subspecies of Palearctic water frogs, genus
      Rana. Although C-banding patterns showed interspecific or intersubspecific
      variation, late replication banding patterns of all 13 chromosome pairs of these
      species were homologous. Minor differences of banding patterns were observed only
      in chromosomes 2, 7 and 13. Close comparison of the late replication banding
      patterns with those of three non-water frog species of Rana, and one each of Hyla
      and Bufo, provided important information on interspecific and intergeneric
      variability. In the Rana species, the banding patterns of all 13 pairs were
      homologous except for those some regions of 8 pairs. In one species each of Hyla
      and Bufo that was examined, the six large chromosome pairs (Nos. 1-6) showed
      banding homologies. Furthermore, among the Rana, Hyla and Bufo species the four
      large chromosome pairs (Nos. 1-3, 5 of Rana and Hyla, and Nos. 1, 3-5 of Bufo)
      shared banding homologies. These results show that the large chromosomes have
      been highly conserved in the evolutionary history of the three genera.

PMID- 7621708
TI  - Immunocytochemical mapping of FMRFamide-like peptides in the argasid tick
      Ornithodoros parkeri and the ixodid tick Dermacentor variabilis.
AB  - FMRFamide-like immunoreactivity was studied in the argasid tick Ornithodoros
      parkeri and the ixodid tick Dermacentor variabilis using immunocytochemistry
      based on the peroxidase-antiperoxidase method. FMRFamide-like immunoreactive
      cells are widely distributed in various regions of the tick synganglion including
      protocerebral, cheliceral, stomodeal, palpal, pedal I-IV, and opisthosomal
      regions in both species. However, there is one layer of immunoreactive cells
      located on the dorsal surface of the postoesophageal part of the synganglion that
      is found only in D. variabilis. Besides the immunoreactivity within the cell body
      and its axons, the neuropile and the neural lamella (the extracellular sheath of
      the synganglion) are rich in immunoreactive materials. Some coxal muscles are
      innervated by the FMRFamide-like immunoreactive processes of the nerve from the
      pedal ganglion.

PMID- 7621709
TI  - Repellent and acaricidal properties of Ocimum suave against Rhipicephalus
      appendiculatus ticks.
AB  - An oil extracted from the leaves of a tropical shrub Ocimum suave was found to
      repel as well as kill all stages of the tick Rhipicephalus appendiculatus. In an
      in vitro bioassay for the larvae, the LC50 of the oil in liquid paraffin was
      0.024%. A 10% solution was found to kill all immatures and more than 70% of
      adults feeding on rabbits. Rabbits were protected for 5 days against attaching
      larvae using a 10% solution. Preliminary experiments undertaken with cattle kept
      in the field suggest that the oil may have potential in tick control, and a role
      in integrated tick management.

PMID- 7621710
TI  - Differences in Borrelia infections in adult Ixodes persulcatus and Ixodes ricinus
      ticks (Acari: Ixodidae) in populations of north-western Russia.
AB  - Dark-field microscopy was used to determine the number of Borrelia spirochetes in
      630 standard preparations obtained from adult ixodid ticks (344 Ixodes
      persulcatus and 286 I. ricinus) collected in 1989-92 in the Leningrad region of
      Russia. The average numbers of Borrelia in I. persulcatus and I. ricinus
      preparations were 34.7 and 23.3 per 100 microscopic fields, respectively. The
      maximal individual values registered each year for ticks of both species were
      several hundred times greater than the minimal values. Ticks carrying relatively
      small numbers of Borrelia generally predominated. Proportions of more heavily
      infected ticks varied considerably from year to year. These parameters were
      significantly higher in foci with predominance of I. persulcatus ticks. As a
      consequence, risk to acquire Lyme borreliosis in such foci is considered greater
      than in foci where I. ricinus predominates.

PMID- 7621711
TI  - Entomopathogenic fungi associated with Ixodes ricinus ticks.
AB  - The objective of this study was to demonstrate the occurrence of entomopathogenic
      fungi on Ixodes ricinus ticks in relation to the tick stage, engorgement and
      season. Ticks were collected from the vegetation, from small rodents and from
      deer. All entomopathogenic fungi found belonged to the Hyphomycetes. Paecilomyces
      farinosus and Verticillium lecanii were the predominant species. Other species,
      found only on engorged females were: Beauveria bassiana, B. brongniartii, P.
      fumosoroseus and V. aranearum. Eight out of 1833 ticks collected from the
      vegetation and three out of 269 engorged nymphs were infected with fungi. Thirty
      three out of 149 engorged females were infected, whereas males and engorged
      larvae were not infected. Throughout the season, a significantly higher
      proportion of ticks collected in autumn were infected. Entomopathogenic fungi may
      have a significant impact on the size of the I. ricinus population, since females
      were the most frequently infected stage.

PMID- 7621712
TI  - Hyalomma truncatum (Acari; Ixodidae): investigations into the scototaxis of unfed
      adult ticks.
AB  - Under controlled test conditions, unfed male and female Hyalomma truncatum ticks
      exhibited a positive scototaxis to stationary, two-dimensional targets. Upright
      positioned rectangles were the most attractive targets. The attractiveness of
      these targets increased with their size. Significantly more ticks responded
      scototactically positively to the targets under a luminance contrast ratio of
      5:1, as compared with other luminance contrast ratios. Targets with an elevation
      angle of 13 degrees were occupied more frequently than objects with higher
      elevation angles. Scototaxis was the same towards a stationary and a sinusoid
      oscillating target. When an upright-positioned rectangle was combined with a CO2
      gradient, the number of ticks that migrated into the CO2 gradient and contacted
      the target did not increase significantly. The interval between exposure and
      first locomotion of the ticks, however, was significantly shorter under the
      influence of a CO2 gradient than in all other experiments without a CO2 gradient.
      A temperature gradient simulating a natural host (cattle) did not alter the
      scototaxis. The results of these investigations suggest that the positive
      scototaxis exhibited by adult H. truncatum ticks is not likely to be part of
      their appetence behaviour but rather searching behaviour to find adequate
      protection from harsh climatic conditions.

PMID- 7621713
TI  - Cancer screening: protecting the public's health.

PMID- 7621714
TI  - Fine-needle aspiration biopsy and imprint cytology of small non-cleaved cell
      (Burkitt's) lymphoma.
AB  - We reviewed 13 cases of small non-cleaved cell (Burkitt's) lymphoma diagnosed by
      fine-needle aspiration biopsy (FNAB) and four cases where that diagnosis was made
      from touch imprints from surgical biopsy specimens. The most common site was
      intraabdominal. Histologic confirmation was present in 14/17 cases. General
      microscopic features on smears included high cellularity and an individual cell
      pattern. Extracellular lymphoglandular bodies were abundant and tingible body
      macrophages were prominent. Nuclei were intermediate in size and round with a
      finely dispersed chromatin pattern on May-Grunwald-Giemsa stained smears.
      Cytoplasm was basophilic and scant with prominent vacuoles. Extracellular
      vacuoles and vacuoles within lymphoglandular bodies occurred in all patients.
      Immunocytochemistry performed on 16/17 cases demonstrated a B cell phenotype in
      15. Nine cases were kappa light chain positive and six were lambda light chain
      positive. Flow cytometry performed in five cases demonstrated diploid cells with
      a high S phase. We conclude that Burkitt's lymphoma can be diagnosed using
      combined FNAB and immunophenotyping.

PMID- 7621716
TI  - Lacrimal gland lymphoma: a cytomorphologic and immunophenotypic study.
AB  - The cytomorphology of lacrimal gland lymphoma has not been specifically
      described. Herein we present six cases of histologically proven lacrimal gland
      lymphoma which we analyzed using fine-needle aspiration cytology, cell suspension
      immunophenotype analysis, and immunoglobulin gene rearrangement studies. Fine
      needle aspiration cytology revealed atypical populations of cells comprised of
      either monomorphic small round lymphocytes with or without plasmacytoid features
      (4 cases), a mixed population of small and large irregular lymphocytes (1 case),
      or a population of large irregular lymphocytes (1 case). The initial cytologic
      diagnosis was malignant lymphoma in all six cases. Cell suspension
      immunophenotype analysis demonstrated that the lesions were composed
      predominantly of B-cells that expressed monotypic surface immunoglobulin. Three
      cases demonstrated an immunoglobulin heavy chain gene rearrangement. The atypical
      cytologic features and the abnormal immunophenotype were consistently predictive
      of malignant lymphoma. Given that these lesions are small and biopsy material is
      often limited, fine-needle aspiration offers the advantage of providing tissue
      that is ideal for cytologic and cell suspension immunophenotype evaluation,
      obviating the need to provide surgical biopsy material for this purpose. We
      conclude that fine-needle aspiration can identify malignant lymphoid lesions of
      the lacrimal gland and may serve as a valuable adjunct in the assessment of these
      lesions. Additional study is warranted to determine whether fine-needle
      aspiration can reliably distinguish between benign and malignant lymphoid
      proliferations of the lacrimal gland.

PMID- 7621715
TI  - Significance of endothelium in the fine-needle aspiration biopsy diagnosis of
      hepatocellular carcinoma.
AB  - We reviewed fine-needle aspiration biopsies (FNAB) of hepatocellular carcinoma
      (HCC) (n = 35), benign hepatic processes (n = 35), cholangiocarcinoma (CC) (n =
      6), and metastatic tumors (n = 100) to evaluate the significance of endothelium
      present either peripherally-wrapping around groups of cells, (peripheral
      endothelium (PE)), or transgressing sheets of cells (transgressing endothelium
      (TE)), in distinguishing these lesions. These patterns were assessed as absent,
      focal, or prominent. Thirty-three of 35 (94%) HCCs contained either focal or
      prominent PE or TE, compared to only 3 of 35 (9%) benign hepatocytic lesions.
      Only one benign lesion contained a prominent endothelial component (TE only). Two
      cases of HCC failed to contain endothelium, one fibrolamellar variant and one
      well-differentiated HCC. These differences were statistically significant (P <
      10(-5), sensitivity 94%, specificity 91%, and positive predictive value [PPV]
      92%). Neither pattern of endothelium was present in any CC or metastatic tumor.
      These differences were also statistically significant (P < 10(-5), sensitivity
      94%, and specificity and PVP 100%). We conclude that the presence of endothelium,
      at least focally in either one or both distinctive patterns, is highly sensitive
      and specific for HCC and aides in distinguishing it from benign hepatocytic
      lesions, CC, and metastases.

PMID- 7621717
TI  - Extragonadal germ cell tumors: a fine-needle aspiration biopsy study.
AB  - Germ cell tumors (GCT) are neoplasms that originate predominately in the ovary
      and testis. Tumors of germ cell origin only very uncommonly arise in extragonadal
      sites. We have diagnosed ten primary malignant extragonadal GCT arising in the
      mediastinum, retroperitoneum, liver, and sacrococcygeal region by fine-needle
      aspiration biopsy (FNAB). Patient ages ranged from 1 to 54 years; the majority
      were males. Our series included three seminomas, three yolk sac tumors (YST), one
      choriocarcinoma, one embryonal carcinoma, and two mixed, poorly differentiated
      GCT. In aspirates, seminomatous elements are dissociated with uniform
      mononucleate cells having large vesicular nuclei and prominent nucleoli. A
      tigroid background is produced with Diff-Quik-stained smears. YST yields cohesive
      clusters of cells with large nuclei, vacuolated cytoplasm, and extracellular
      hyaline matrix (spheres or hyaline globules). Giant multinucleate tumor cells are
      seen in choriocarcinoma. Embryonal carcinoma yields cellular smears of
      hyperchromatic cells with scant cytoplasm arranged predominantly in glandular or
      papillary formations. Ultrastructural (four cases) and immunocytochemical (seven
      cases) studies of aspirated material corroborated our cytologic interpretations.
      Aneuploid tumor cells were found by flow cytometry in aspirated material from a
      YST. Subsequent histologic examinations were performed on eight, and all were
      confirmatory. Although extragonadal GCT are relatively uncommon, they need to be
      considered in FNAB material from midline mass lesions. Ancillary studies were
      useful in confirming their diagnosis.

PMID- 7621719
TI  - Melanoma with signet-ring cells in a peritoneal effusion.
AB  - Melanoma may occasionally give rise to a malignant effusion and when this occurs
      it can present a challenging differential diagnosis. We present such a patient
      who developed a peritoneal effusion. Cytologic examination of the peritoneal
      fluid revealed individual malignant cells with prominent cytoplasmic vacuoles
      raising the possibility of a signet-ring cell adenocarcinoma. Immunohistochemical
      studies were indicative of a malignant melanoma. In this case we believe that the
      cytoplasmic vacuoles may be a degenerative phenomenon and as such may represent
      another mechanism for the development of a signet-ring morphology in malignant
      melanoma.

PMID- 7621718
TI  - Growth fraction in non-Hodgkin's lymphomas and reactive lymphadenitis determined
      by Ki-67 monoclonal antibody in fine-needle aspirates.
AB  - The fraction of proliferation cells was analysed in fine needle aspirates from a
      series of 448 non-Hodgkin's lymphomas and 199 reactive hyperplasias using an
      immunoperoxidase staining with monoclonal antibody Ki-67. There was a good
      correlation between proliferation fraction and cytologic assignment to high and
      low grade lymphomas. Thus high grade lymphomas had a high median percentage of Ki
      67 positive cells with a figure of 82.1 for lymphoblastic, 60.0 for
      immunoblastic, and 59.7 for centroblastic lymphomas. For low grade lymphomas the
      figures were 17.1 and 11.1 percent for centroblastic/centrocytic and
      CLL/immunocytoma, respectively. The fraction of proliferation cells in reactive
      lymphadenitis varied between 1-50% with a median of 11.5%. Analysis of Ki-67
      positivity can accordingly not be used to differentiate benign from neoplastic
      proliferations. Within all lymphoma subgroups but lymphoblastic lymphoma, there
      was a marked variation in fraction of Ki-67 positive cells, which resulted in a
      certain overlap between high and low grade lymphomas. The results show that cells
      procured through fine-needle aspiration can be used to analyse the fraction of
      proliferating cells which contributes information about the growth rate of the
      individual tumours that can not be obtained through cytologic classification.

PMID- 7621720
TI  - Adenomyoepithelioma of the breast: fine-needle aspiration biopsy and histologic
      findings.
AB  - Adenomyoepithelioma is an uncommon tumor of the breast which clinically presents
      as a discrete nodule and histologically is composed of lumenal spaces lined by a
      mixture of epithelial and myoepithelial cells. It has a spectrum of histologic
      appearances which are gradually gaining wider recognition. There are, however,
      only a few descriptions of the fine-needle aspiration biopsy (FNAB) findings in
      adenomyoepithelioma. We report the FNAB and histologic features of a mammary
      adenomyoepithelioma which contained a prominent epithelial component including a
      focus of marked epithelial atypia. This expands the spectrum of FNAB findings
      which have been reported in adenomyoepithelioma.

PMID- 7621721
TI  - Fine-needle aspiration diagnosis of extrapulmonary Pneumocystis carinii
      lymphadenitis in a human immunodeficiency virus positive patient.
AB  - Extrapulmonary Pneumocystitis carinii is an uncommon and probably underdiagnosed
      complication of pulmonary P. carinii infections. We report the cytologic
      diagnosis of a case of P. carinii lymphadenitis which presented, without
      concurrent or historical pneumonitis, in a human immunodeficiency virus (HIV)
      positive patient who was taking aerosolized pentamidine. The diagnosis was
      suggested by abundant granular exudate on the cell block. Only scant, fragmented,
      irregular-shaped granular exudate was present on the direct smears and the
      Millipore filter preparation. The diagnosis was confirmed by special stains on
      the cell block.

PMID- 7621722
TI  - Cytopathological features of undifferentiated carcinoma of the ovary.
AB  - Cytopathological characteristics of undifferentiated carcinoma of the ovary were
      examined and reviewed. Seven cases of undifferentiated carcinoma were encountered
      among 202 malignant ovarian neoplasms in the Saitama Cancer Center.
      Histologically, two cases contained a minor component of usual Mullerian
      carcinoma and five others were purely of solid architecture without
      differentiation. Nevertheless, six cases, four of which were totally
      undifferentiated histologically, showed cytological features characteristic of
      adenocarcinoma. The results indicate that even carcinomas histologically
      diagnosed as undifferentiated may have cytological features of glandular
      differentiation, which may be Mullerian in origin.

PMID- 7621723
TI  - Aspiration cytodiagnosis of metastatic Merkel-cell carcinoma.
AB  - A case of metastatic Merkel-cell carcinoma to lymph nodes on the left side of the
      neck and left parotid is described. The primary was at the left side of the cheek
      and bridge of the nose. The cytologic features in needle aspirates of metastases
      included increased cellularity, discohesive or loose groups of small-to-medium
      size malignant cells with uniform, round-to-oval nuclei, delicate nuclear
      membranes, fine chromatin, multiple micronucleoli, and scanty cytoplasm.
      Additionally, rare intermediate filament "buttons" and frequent mitotic figures
      were found. The primary tumour showed similar features. On immunostaining,
      although a positivity for chromogranin was noted in the primary tumour, it was
      found to be negative in the cytologic material. All other histochemical and
      immunostains were found to be negative in both the primary and metastatic
      neoplasm. The problems in differential diagnosis from other small cell tumours
      and the features of this unique tumour that may be helpful in the diagnosis are
      discussed.

PMID- 7621724
TI  - Endometrial cells of the "lower uterine segment" (LUS) in cervical smears
      obtained by endocervical brushings: a source of potential diagnostic pitfall.
AB  - The use of endocervical brushes has led to a generous sampling of both
      endocervical and "lower uterine segment" (LUS) cells. To an unfamiliar eye, the
      large fragments of endometrial tissue from the LUS may lead to misinterpretation
      as endometriosis or glandular malignancy, as happened in our institution when the
      use of endocervical brush and recognition of LUS cells in cervical smears were
      limited. Eight cases, cytologically interpreted as such, were proven to be benign
      following cervical biopsy or endometrial curettage. The nature of LUS cells was
      recognized only on retrospective review of this cytologic material. However, in
      recent years, routine use of the endocervical brush resulted in an influx of
      similar cases referred by the cytotechnologists to the pathologist as glandular
      atypia. Thus, to get familiarized with the cytomorphology of LUS cells and its
      diagnostic pitfalls, a prospective study was undertaken. This entailed a review
      of 62,187 consecutive cervicovaginal smears (women of post-hysterectomy status
      were excluded) received within a 12-mo period (July 1, 1992-June 30, 1993). A
      total of 344 smears (0.55%) showed large tissue fragments of branching tubular
      endometrial glands with and without surrounding stroma. Patients ranged from 14
      82 yr of age. History of cervical cone biopsy was noted in nine patients (2.6%).
      Repeat cervical smear or concurrent endometrial or endocervical biopsy available
      in 84 patients (24.4%) were negative. LUS cells may be mistaken for
      endometriosis, epithelial glandular atypia, as well as carcinoma of both
      endocervical and endometrial origin. In addition to glandular abnormality, LUS
      cells may also be misinterpreted as that of squamous intraepithelial
      lesion.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7621725
TI  - Two unusual benign lesions of the neck masquerading as malignancy on fine-needle
      aspiration cytology.
AB  - Two cases of unusual benign tumors of the neck are described, both of which were
      initially misdiagnosed on cytology as carcinomas. Fine-needle aspiration findings
      in each case demonstrated a pleomorphic population of cells including bizarre
      multinucleated giant cells, the latter raising the false impression of
      malignancy. However, on review the cytological appearances of the tumors, a
      pleomorphic lipoma and a carotid body tumor, were characteristic. The correct
      diagnosis in each case would have been made or suggested if the pathologist had
      been familiar with the cytologic features characteristic of the lesion and the
      differential diagnosis of the head and neck tumors. In addition, the point is
      made that adequate clinical information is essential for the pathologist if all
      relevant conditions are not to be missed in the differential diagnosis.

PMID- 7621726
TI  - Unsatisfactory aspirates from fine-needle aspiration biopsies: a review.
AB  - While there is much evidence that fine-needle aspiration biopsy (FNAB) is
      sensitive and specific, there is little information comparing the proportions of
      unsatisfactory aspirates obtained by clinicians or pathologists. We reviewed
      2,199 FNAB reports of superficial lesions. Cases were grouped by organ/site and
      according to who performed the biopsy. The proportions of unsatisfactory
      aspirates were computed for clinicians and pathologists. Both groups performed
      approximately equal numbers of procedures. Overall, 9% of aspirates obtained were
      unsatisfactory (n = 191). Pathologists had lower proportions of unsatisfactory
      aspirates in all sites. Of aspirates obtained by clinicians, 14% were
      unsatisfactory, compared to 3% of those obtained by pathologists (P < .00001).
      The proportion of unsatisfactory aspirates appears to decrease as physician
      experience increases, and pathologists may have more experience with FNAB than do
      clinicians. Other advantages pathologists may have include technique and working
      with tissue regularly. Both clinicians and pathologists can expect to decrease
      their proportions of unsatisfactory aspirates by performing FNABs frequently.

PMID- 7621727
TI  - Wuchereria bancrofti in BAL fluid of a woman with a concomitant breast lesion.

PMID- 7621728
TI  - From the president: "take me to your leader"--reflections on leadership and life.

PMID- 7621729
TI  - Drug/drug and drug/disease interactions and diabetes.

PMID- 7621730
TI  - Aspiration of the subcutaneous insulin injection: clinical evaluation of needle
      size and amount of subcutaneous fat.
AB  - Investigating the rationale for a particular technique can reveal the surprising
      finding that some techniques are not based on scientific research. Aspiration of
      the insulin syringe is an example of a technique that evolved based on
      assumption. In a study designed to challenge the need to aspirate during insulin
      administration, 204 injections that were aspirated yielded no blood return. The
      historical and research literature supports the finding that aspiration never was
      proven to be a reliable indicator of correct subcutaneous needle placement.
      Because inadvertent intramuscular injection of insulin has been documented,
      diabetes educators need a reliable method to individualize insulin administration
      techniques to decrease the risk of incorrect needle placement. Until a reliable
      method is available, the literature supports lifting a skinfold for all
      subcutaneous insulin injections.

PMID- 7621731
TI  - Psychosocial challenges for children with insulin-dependent diabetes mellitus.
AB  - This article describes the particular relevance of Erik Erikson's psychosocial
      stages of development for children with insulin-dependent diabetes. The
      developmental issues for young children centering on trust, autonomy, initiative,
      and industry have special significance for children with diabetes. Although the
      issues faced in each of Erikson's psychosocial stages are present in every stage,
      behaviors are manifested differently at each stage. Practical suggestions are
      provided for families and healthcare providers living with or working with
      children of various ages who have diabetes.

PMID- 7621732
TI  - Personal models of diabetes among older adults: relationship to self-management
      and other variables.
AB  - The purpose of this study was to test whether older patients' personal models of
      diabetes predict their levels of self-management activities (dietary intake,
      physical activity, and blood glucose testing) and glycemic control. The Personal
      Models of Diabetes Interview (PMDI) was administered on two occasions to 78
      patients (> or = 60 years) with non-insulin-dependent diabetes mellitus. Self
      management behaviors, quality of life, and affect were assessed on the second
      occasion and at 4 months. Glycemic control was assessed at 4 months. Three
      constructs of the PMDI (cause, treatment effectiveness, and seriousness) were
      correlated significantly with several aspects of quality of life and with
      negative affect. Personal models, especially beliefs regarding treatment
      effectiveness, were predictive of dietary intake and physical activity but not
      blood glucose testing. Assessing patients' personal models is valuable for
      individualizing education and counseling for nutrition and physical activity, and
      selecting strategies consistent with patients' perspectives.

PMID- 7621733
TI  - Guidelines for facilitating a patient empowerment program.
AB  - The traditional medical treatment model often ignores the emotional, spiritual,
      social, and cognitive aspects of living with a chronic disease such as diabetes.
      Empowerment programs address these psychosocial areas by helping individuals
      develop skills and self-awareness in goal setting, problem solving, stress
      management, coping, social support, and motivation. Although many diabetes
      educators have been taught to use an empowerment curriculum to facilitate self
      management, there is minimal research concerning the actual process of providing
      such programs to patients. We evaluated an empowerment curriculum (Empowerment: A
      Personal Path to Self-Care) with a diverse group of individuals with diabetes to
      determine the key elements of planning and implementing a successful diabetes
      patient empowerment program.

PMID- 7621734
TI  - Using telecommunication technology to manage children with diabetes: the Computer
      Linked Outpatient Clinic (CLOC) Study.
AB  - The purpose of this study was to evaluate the efficacy of using a
      telecommunication system to assist in the outpatient management of pediatric
      patients with insulin-dependent diabetes. Metabolic control, patients'
      psychosocial status, family functioning, perceived quality of life, patterns of
      parental/child responsibility for daily diabetes maintenance, and nursing time-on
      task were evaluated. One hundred six pediatric patients (mean age = 13.3 years)
      were randomly assigned to an experimental or control outpatient clinic for 1
      year. Experimental subjects transmitted self-monitoring blood glucose data by
      modem to the hospital every 2 weeks. Transmitted data were reviewed by nurse
      practitioners who telephoned subjects to discuss regimen adjustments. Control
      subjects received standard care with regimen adjustments made by physicians.
      There were no significant between-group differences for metabolic control, rates
      of hospitalization or emergency-room visits, psychological status, general family
      functioning, quality of life, or parent-child responsibility. A significant
      decrease was noted in nursing time-on-task for experimental subjects.

PMID- 7621735
TI  - An anatomical creative foot model: teaching and learning excellence in
      prevention.

PMID- 7621736
TI  - [Globus sensation].

PMID- 7621738
TI  - [Limits of knowledge and action in medicine].

PMID- 7621737
TI  - [Platelet activation and platelet aggregation in the arteriosclerotic
      endothelium: pathophysiological aspects and new therapeutic concepts].

PMID- 7621739
TI  - [Conservative treatment of spontaneous cerebral hematomas].

PMID- 7621740
TI  - [Successful plasmapheresis in severe diltiazem poisoning].

PMID- 7621741
TI  - [Successful plasmapheresis in severe diltiazem poisoning].

PMID- 7621742
TI  - [Prevention of heterotopic ossification by radiotherapy following total hip
      prosthesis].
AB  - BACKGROUND: Clinically relevant heterotopic bone formation (HBF) following total
      hip arthroplasty (THA) occurs in about one third of all high risk patients. HBF
      can reduce the functional result of surgery by pain and limited range of motion.
      The experience with patients treated with postoperative radiation therapy after
      THA with or without removal of HBF is reported. PATIENTS AND METHOD: Between
      November 1986 und June 1993, postoperative irradiation was performed on 238 hips
      of 216 patients (117 men, 99 women, median age 66 years, range 38-86 years) with
      defined risk factors using 10 Gy in 5 fractions (n = 176) or 7 Gy in one fraction
      (n = 62) with a cobalt unit. In general, irradiation was performed during the
      first four postoperative days after primary THA alone in 182 hips or removal of
      HTB in 56 hips with (n = 28) or without (n = 28) revision surgery. Risk factors
      for HBF were preexisting ipsi- or contralateral HBF in 105 hips (group 1) or
      hypertrophic osteoarthritis, previous operative procedures of the hip and others
      in 134 hips (group 2). After a follow-up of at least 6 months patients were
      examined and radiographs of the hip were performed to classify HBF. RESULTS: New
      or progressive ossifications had developed in the interval in 15 of 104 hips of
      group 1 (14.4%), compared with 19 of 134 hips in group 2 (14.2%). Clinically
      significant new HBF (grade 3 or 4) occurred in none of group 2, and in 3 hips of
      group 1 (2.9%). After radiation with 10 Gy HBF of all grades occurred in 23 of
      176 hips (13.1%), and in nine of 62 hips after 7 Gy (14.5%). The lowest number of
      treatment failures was found in patients irradiated during the first 4
      postoperative days. CONCLUSION: These results demonstrate that immediate
      postoperative radiation is efficacious for prevention of clinically relevant HBF
      following THA and removal of HBF.

PMID- 7621743
TI  - [Type I cryoglobulinemia].
AB  - HISTORY AND CLINICAL FINDINGS: For 2 years a 52-year-old man had repeated bouts
      of purpura, arthralgia and fever. He was known to have abnormal monoclonal
      gammaglobulins, type IgG-lambda and vasculitis when he had another bout with
      acute renal failure and necrotizing ulcers in the legs. TESTS: Several laboratory
      tests were abnormal: erythrocyte sedimentation rate (122 mm), haemoglobin level
      (9.1 g/dl), white cell count (32,000/microliters), platelet count
      (562,000/microliters), creatinine level (4.1 mg/dl) and liver enzyme activities.
      He also had proteinuria (4.5 g daily) and nephritic urinary sediments. The
      immunoglobulin was subtype IgG3, and a cryoglobulinaemia was also present. Total
      complement level (CH 50) was not measurable. Bone marrow aspirate revealed
      plasmocytoma infiltration, and renal biopsy demonstrated necrotizing arteritis,
      as well as granular subendothelial deposits of IgG and complement. TREATMENT AND
      COURSE: After three plasma separations and initiation of the first treatment
      cycle with a four-day infusion of vincristine, doxorubicin and dexamethasone the
      creatinine concentration fell to within the normal range and the necroses healed
      slowly. No cryoglobulin activity has been demonstrable over the past 24 months.

PMID- 7621744
TI  - [Percutaneous extracorporeal circulation in cardiogenic shock caused by combined
      poisoning with methyldigoxin, nifedipine and indapamide].
AB  - HISTORY AND FINDINGS: A 38-year-old man with endogenous depression was found
      comatose and with gasping respiration. Empty packets of tablets pointed to
      poisoning with methyldigoxin, nifedipine and indapamide. Pupils reacted slowly to
      light and no peripheral blood pressure could be measured. TREATMENT AND COURSE:
      Routine resuscitation measures (intubation, mechanical ventilation, external
      cardiac massage and drugs) were undertaken during transport to hospital where, in
      addition to further symptomatic treatment, digoxin antibodies were administered,
      but without noticeable effect. Percutaneous cardiopulmonary bypass was therefore
      undertaken. It achieved a cardiac output of 3.2l and a systolic pressure of 80 mm
      Hg: a stable rhythm and circulation were obtained within 15 hours indicating that
      electromechanical uncoupling had for the time being been overcome. The EEG
      suggested a midbrain syndrome. After another 18 hours of mechanical ventilation
      and symptomatic treatment asystole suddenly occurred. Renewed resuscitation
      procedures were not undertaken because of the very poor neurological state and
      prognosis. CONCLUSION: Although haemodynamic stabilization was only temporarily
      achieved and the patient's death could not be prevented because of adverse
      pretreatment conditions, the application of percutaneously implantable,
      transportable heart-lung machine appears to be justified in cases of intoxication
      with cardio- and vasodepressive substances.

PMID- 7621745
TI  - Vasoactive intestinal peptide: an important trophic factor and developmental
      regulator?
AB  - It has been proposed that vasoactive intestinal peptide (VIP) or a very closely
      related peptide has important actions very early in embryonic development. Recent
      data supporting this hypothesis are that subnanomolar concentrations of VIP
      significantly increased the growth rate of cultured embryonic day-9.5 (E9.5)
      mouse embryos, and that embryos at this and later stages exhibit a high degree of
      VIP binding in the brain stem and spinal cord. It is not known whether VIP is
      derived from the fetus, placenta, or mother at these early stages, or whether VIP
      acts in this culture system in place of a related peptide. The earliest reported
      expression of VIP in rat embryos is at E13.5, when the peptide and mRNA are
      expressed transiently in a high percentage of cells in the rat stellate ganglia.
      The time course of events mapped in other sympathetic ganglia at this stage
      suggest that transient expression of VIP in the ganglia might function to
      regulate neuroblast and/or glial cell proliferation, maturation or survival.
      Tissue culture studies indicate that VIP can support many of these trophic
      functions at concentrations that are the same or lower than that necessary to
      increase cAMP levels by way of classical VIP receptors. For example, VIP at 10(
      10) M stimulates the release of neurotrophic factors from glial cells and
      maximally stimulates the proliferation of astrocytes. Two VIP receptors encoded
      on different genes have now been cloned. Both are members of the seven
      transmembrane G-protein-coupled receptor family and, when expressed in mammalian
      cells, mediate an increase in cAMP.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7621748
TI  - Pretreatment with MK-801 inhibits pemoline-induced self-biting behavior in
      prepubertal rats.
AB  - The indirect dopamine agonist, pemoline (120-300 mg/kg s.c.), can induce self
      biting behavior in the rat. The present study demonstrates that the non
      competitive N-methyl-D-aspartate (NMDA) antagonist, dizocilpine (MK-801, 0.2
      mg/kg s.c.), significantly attenuates pemoline-induced self-biting behavior,
      while simultaneously increasing locomotor activity. When animals received a fixed
      dose of MK-801 with increasing doses of pemoline, a competitive relationship
      emerged such that high-dose pemoline surmounted the antagonistic effect of MK
      801. In contrast to spiperone, delayed administration of MK-801 was ineffective
      in blocking the subsequent expression of self-biting behavior, suggesting that
      dizocilpine exerts its protective effect early in the cascade of events which
      eventually leads to self-biting behavior in this paradigm.

PMID- 7621747
TI  - Axonal-growth-associated intracellular molecule in the rat central nervous system
      recognized by the monoclonal antibody 5H.
AB  - In order to discover molecules involved in axonal outgrowth during development of
      the central nervous system (CNS), monoclonal antibodies (MAbs) were raised
      against homogenates of the early postnatal rat cerebral cortex. A novel MAb, 5H,
      was obtained which recognizes a developmentally regulated antigen in the CNS. In
      the cerebral cortex of postnatal (PN) day 0-6 rats, 5H-immunoreactive punctate or
      fiber-like processes were observed. In the PN day 12 cortex, 5H immunostaining
      was mostly present as puncta. The expression of the 5H antigens decreased in the
      second PN week and completely disappeared from the cortex of rats older than PN
      day 18. In the hippocampal region, 5H immunoreactivity exhibited similar
      developmental changes, but with a more prolonged period of expression of the
      antigen (up to 5 weeks postnatally). They were also absent from the hippocampus
      of the adult rat. Similar developmental changes were also observed in the other
      CNS regions, but the only region in the adult CNS that showed 5H immunoreactivity
      was the olfactory bulb, in which synaptic turnover normally occurs even in the
      adult. Immunoelectron microscopy revealed that 5H immunoreactivity was localized
      to the cytoplasm of neuronal processes, including synaptic boutons. The
      expression of the 5H antigen in neurons cultured from rat cerebral cortex
      obtained from embryonic day 16 to PN day 6 was mostly restricted to neurite tips,
      including growth cones. These results suggest that the MAb 5H antigen is
      associated with axonal outgrowth during early development in the CNS.

PMID- 7621746
TI  - FAC1, a novel gene identified with the monoclonal antibody Alz50, is
      developmentally regulated in human brain.
AB  - The monoclonal antibody Alz50 recognizes both neurofibrillary pathology
      associated with Alzheimer's disease and subplate neurons in the developing human
      brain. To attempt to identify Alz50 antigens expressed during development, a
      human fetal brain cDNA library was immunoscreened. A positive clone was isolated
      and sequenced. The clone represents a novel gene named FAC1 (Fetal Alz-50
      Reactive Clone 1). The FAC1 gene is located on human chromosome 17 and is
      conserved across species. In the human fetal brain, the FAC1 gene product is
      abundantly expressed and the protein is located both in the nucleus and the
      cytoplasm of cells throughout the developing cortex. Decreased levels of FAC1
      protein are observed in adult brain by immunoblot analysis. By
      immunocytochemistry, the FAC1 protein is almost exclusively localized in the
      nucleus of neurons in the adult neocortex. Therefore, expression of the FAC1 gene
      is developmentally regulated and the cellular localization of the protein product
      is altered during development.

PMID- 7621749
TI  - Course and collaterals of corticospinal fibers arising from the sensorimotor
      cortex of the reeler mouse.
AB  - The reeler genetic mutation, occurring spontaneously in mice, affects migration
      of neuroblasts in the central nervous system at its last stage, causing severe
      cytoarchitectonic abnormalities in laminated structures, such as the cerebral and
      cerebellar cortex. In the reeler mouse, corticospinal (CS) neurons are
      malpositioned in association with the deranged laminar cytoarchitecture. To
      examine whether CS projections in the reeler mouse and their collaterals
      terminating with subcortical nuclei are normal or not, 5% biocytin was injected
      into the sensorimotor cortex of 2-month-old normal and reeler mice. Anterogradely
      labeled CS fibers of normal and reeler mice exited from the cortex and entered
      the internal capsule and the cerebral peduncle. They penetrated the basal pontine
      gray matter as longitudinal pontine fibers and entered the medullary pyramid.
      They continued caudally as a compact bundle along the ventral surface of the
      medulla, passed through the pyramidal decussation at the spinomedullary junction
      and entered the contralateral dorsal funiculus of the spinal cord. Both in normal
      and reeler mice, collaterals arising from these CS fibers projected to the
      ipsilateral red nucleus, basal pontine gray matter, inferior olivary complex, and
      the contralateral gracile nucleus. Thus, in the reeler mouse, the course and
      termination of CS fibers and their collaterals are identical to their normal
      counterparts, suggesting that radially malpositioned CS neurons in the
      sensorimotor cortex project to the subcortical nuclei in a manner similar to
      normal CS neurons.

PMID- 7621750
TI  - Traditional dental practices.

PMID- 7621751
TI  - Removal of deciduous canine tooth buds in Kenyan rural Maasai.
AB  - The removal of deciduous canine tooth buds in early childhood is a practice that
      has been documented in Kenya and in neighboring countries. This paper describes
      the occurrence, rationale and method of this practice amongst rural Kenyan
      Maasai. In a group of 95 children aged between six months and two years, who were
      examined in 1991/92, 87% were found to have undergone the removal of one or more
      deciduous canine tooth buds. In an older age group (3-7 years of age), 72% of the
      111 children examined exhibited missing mandibular or maxillary deciduous
      canines. It was found that the actual removal of a deciduous tooth bud is often
      performed by middle-aged Maasai women who enucleate the developing tooth using a
      pointed pen-knife. There exists a strong belief among the Maasai that diarrhoea,
      vomiting and other febrile illnesses of early childhood are caused by the
      gingival swelling over the canine region, and which is thought to contain 'worms'
      or 'nylon' teeth. The immediate and long-term hazards of this practice include
      profuse bleeding, infection and damage to the developing permanent canines. A
      multi-disciplinary approach involving social anthropologists in addition to
      dental and medical personnel, is recommend in order to discourage this harmful
      operation that appears to be on the increase.

PMID- 7621753
TI  - Discolouration of teeth: an overview of the diagnosis and management.
AB  - The dentist is faced with a daunting task in application of clinical skills to
      achieve maximum cosmetic results when it comes to the management of discoloured
      and/or hypoplastic dentition. In this paper, an overview is made of the diagnosis
      and the management of these broadly termed conditions and the cost-effectiveness
      of the various modalities discussed.

PMID- 7621752
TI  - Malocclusion in children aged 3-6 years in Nairobi, Kenya.
AB  - The prevalence of malocclusion in the deciduous dentition of 221 children aged 3
      6 years in Nairobi, Kenya is reported. The children were drawn from six randomly
      selected preprimary schools (kindergarten, nurseries, and pre-units) from
      different areas of the city. Overall, 51% of the children were found to have some
      form of malocclusion. Maxillary overjet accounted for 13%, deep bite 13%, dental
      midline displacement 6%, frontal openbite 12% and anterior crossbite 5%.
      Anthropoid spaces were observed in 85% of the children, while over 60% had
      spacing in the incisor region. Straight terminal plane of the deciduous second
      molars was diagnosed in 53% of the children, mesial step in 43% and distal step
      occlusion in one percent of the children. The results suggest a need for
      interceptive orthodontic treatment in some of the children.

PMID- 7621754
TI  - Association of human rotavirus infection and intestinal rotavirus-specific
      immunoglobulin A in children with diarrhoea.
AB  - The purpose of this study was to determine the role of intestinal specific
      rotavirus IgA antibody in protection against diarrhoea due to rotavirus
      infection. Stool from children aged below 5 years with diarrhoea who reported to
      the Paediatric Observation Ward, Kenyatta National Hospital were examined for
      micro-organisms and IgA antibody. Specific rotavirus IgA antibody and antigen
      were determined using enzyme linked immunosorbent assay technique. Out of 153
      stool specimens, 22% (34/153) were positive for rotavirus antigen and 15%
      (23/153) had IgA specific antibody to rotavirus. Children with specific IgA to
      rotavirus had no rotavirus except in two cases (p < 0.05). There was no
      difference in levels of specific IgA antibody between normal and malnourished
      children (p = 0.4). It is probable that intestinal specific IgA to rotavirus
      protects children against rotavirus diarrhoea.

PMID- 7621755
TI  - Nosocomial rotavirus infection in newborns.
AB  - A total of 252 faecal samples were collected from 84 neonates and examined for
      rotavirus antigen, using the enzyme-linked immunosorbent assay (ELISA).
      Nosocomial rotavirus infection was detected in 23.8%. This was made up of 12
      (26.7%) of 45 neonates who had diarrhoea and 8 (20.5%) of 39 neonates without
      diarrhoea. However, rotavirus antigen was detected more in those that stayed for
      more than one week during hospital admission.

PMID- 7621756
TI  - Effect of non-tuberculous Mycobacteria infection on tuberculin results among
      primary school children in Kenya.
AB  - Few tuberculosis studies carried out in Kenya since 1948 have reported on the
      variations of the occurrence and geographical distributions of non-tuberculous
      Mycobacteria infection. They have however not been able to clearly relate
      infection outcome to the use of tuberculin tests as epidemiologic and clinical
      tool. The present survey, conducted by Kenya Medical Research Institute in
      collaboration with the International Union Against Tuberculosis and Lung Diseases
      between 1986 and 1990 among school children aged 6-13 years in 18 randomly
      selected districts, investigated the following: the prevalence of sensitivity to
      tuberculin PPD RT 23 and PPD scrofulaceum RS 95 sensitin; geographic distribution
      of the reactions from the tests and; the influence of non-tuberculous
      Mycobacteria on the tuberculin results. The WHO cluster sampling procedures were
      used to select 30 schools in each of the 18 districts. Each child was tested with
      an intradermal dose of 2 TU of PPD RT 23 with Tween 80 (PPD RT 23) on the right
      hand and 2 TU of PPD Scrofulaceum RS 95 sensitin with tween 80 (PPD RS 95) on the
      left hand. The results were read after 72 hours of testing. A total of 1015 BCG
      scar negative children was included in the survey. Of these, 981 were tested and
      read. Over 47% of the children did not react to both antigens while 6.1% and
      22.7% reacted to human type tuberculin and environmental sensitin respectively.
      There was cross reaction between the two tests in 23.8% of the children from low
      altitude area who had more and larger reaction to the tests than the middle and
      higher altitude regions of the country.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7621757
TI  - Frequency of antimicrobial resistance and plasmid profiles of Escherichia coli
      strains isolated from milk.
AB  - Susceptibility to eight commonly used antimicrobial agents and plasmid profile
      analysis was done on forty one Escherichia coli strains isolated from milk. Most
      (95%) of the strains were resistant to sulphamethoxazole with a relatively low
      rate of resistance to the other antimicrobial agents. Twenty nine per cent of the
      isolates showed multiple resistance. The number of plasmids carried per strain
      was between 1 and 5, while plasmid sizes ranged between 107 and 1.0 megadaltons
      (MDa). There was no relationship between carriage of plasmids and antimicrobial
      resistance patterns.

PMID- 7621758
TI  - Thyroid cancers in Ibadan, Nigeria.
AB  - Recent reviews of thyroid malignancies indicate an increasing incidence with
      suggestions that incidence and regional variation in histological types may be
      related to socioeconomic and environmental factors. We studied 137 cases of
      thyroid cancer occurring in the University College Hospital, Ibadan over a 20
      year period (1965-1984), consisting of 45 males and 92 females. The ages ranged
      from 8-85 years with a mean age of 40 years. Papillary carcinoma constituted
      45.3% cases, whilst follicular carcinoma made up 44.5% with a frequency ratio of
      1:1. Seven cases (5%) of medullary carcinoma were seen and these had a
      male/female ratio of 1.3:1 with an average age of occurrence of 34 years. In
      contrast to previous studies from this environment, there is a suggestion of an
      increasing trend in the incidence of papillary carcinoma in our centre. The
      significance of changing socio-economic and environmental factors in the region
      are highlighted.

PMID- 7621759
TI  - Outcome of functional psychoses in metropolitan Lagos, Nigeria.
AB  - In a study of 43 psychotics resident in a large metropolitan community of a non
      Western country, scores of defined measures of illness outcome namely symptom
      score, social impairment score, change in occupational status score, indicate a
      generally poor prognosis in functional psychoses. This is congruent with the
      reports of similar studies in the industrialised countries and curiously at
      variance with the reports of better prognosis for several African and Asian
      patients. Our findings might be due to the fact that the population studied was
      exposed to significant western influence or contained poor prognosis illness
      variants. Alternatively, functional psychoses might run different courses among
      different ethnic groups within the same country. Our tentative findings should be
      base-stimulus for further enquiry.

PMID- 7621760
TI  - A longitudinal health interview survey in rural Kenya: potentials and limitations
      for local planning.
AB  - A twelve-month longitudinal household health interview survey in Machakos
      District (now Makueni District), Kenya, during 1991 covered 390 households
      randomly selected from 12 village clusters. The survey focused on recent disease
      symptoms and signs, illness severity, temporary disability and care-seeking
      behaviour. The total number of reported disease episodes was 9,393, (4.4 per
      person) with more episodes reported by adult females than by adult males. The
      disease pattern was dominated by malaria (39.6% of all reported episodes) and
      respiratory tract diseases (23.1%), followed by gastrointestinal illness (10.7%),
      joint/muscle disorders (6.4%), injuries (5.4%) and skin conditions (4.8%). Self
      medication took place in 39.9% of episodes, while care was sought at hospitals or
      clinics in 32.1%. This survey generated information useful for local health care
      planning and management, especially regarding local perception of illness
      episodes and health care utilization. Respondents developed signs of interview
      fatigue, however, and the completeness and accuracy of symptom descriptions by
      the lay interviewers are uncertain. Survey costs were about USD 24,700, one third
      of which was spent on field work, another third on computerized data processing.
      Utility in relation to costs is likely to be modest. Improvement of the health
      information system for local planning and management may be equally or better
      served by selective improvement of the existing routine reporting system combined
      with occasional cross-sectional household surveys.

PMID- 7621761
TI  - Cost-effectiveness of managing abortions: manual vacuum aspiration (MVA) compared
      to evacuation by curettage in Tanzania.
AB  - Cost effectiveness of managing 107 incomplete abortions by manual vacuum
      aspiration (MVA) is compared with management of 92 incomplete abortions by
      evacuation by curettage (E by C) at Muhimbili Medical Centre (September-November
      1992). Pre-evacuation waiting times, duration of procedures and duration of
      hospital stay were less for MVA as compared to E by C. The total pre-evacuation
      waiting time, the durations of the procedure and hospital stay were 15.59 days
      (55.11%), 10.96 (46.41%) hours and 21.23 (40.53%) days less for MVA as compared
      to E by C. The direct costs revealed a cost differential of MVA over E by C of
      Tshs 776.9 (US$2.6). MVA is more cost effective than contemporary E by C and its
      introduction on a wider scale in our health care delivery system is recommended.

PMID- 7621762
TI  - Birth asphyxia: a review.
AB  - Birth asphyxia occurs world wide and remains a serious cause of morbidity of the
      newborn. Its incidence and associated sequelae have remained high in the
      developing world with an attendant high mortality as compared to more affluent
      societies or the developed world. We have attempted in this review, to proffer an
      assessment, prevention strategies and detailed management of birth asphyxia with
      particular reference to the tropics and sub-tropics. A continuous surveillance of
      this problem is highly essential and so is the strict use of facilities at our
      disposal; clinical screening and partography for example, as these could keep a
      rising incidence in check.

PMID- 7621763
TI  - Normal values for lung function tests in Sudanese children.
AB  - Forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and
      peak expiratory flow rates (PEFR) were determined in 400 healthy Sudanese school
      children aged between seven and 12 years aiming to establish normal values of
      lung indices. Both Wright's and Mini Wright's Peak Flow Metres (PFM) were used to
      measure the PEFR. The results were analysed with respect to age, weight, standing
      and sitting heights and the correlation coefficients (r) were calculated. Among
      the variable used, standing height (H) showed the best correlation with PEFR (r =
      0.97) and with FEV1 (r = 0.90). The scatter diagrams produced by plotting the
      values of each of the lung function indices against age, weight, or height were
      comparable. Readings obtained using Mini Wright's PFM were higher than those of
      the wright's by a mean of 18.0 and 16.0 litres for boys and girls, respectively,
      Prediction formulae for mean points have been produced with age and standing
      heights as independent variables. The indices of Sudanese children are similar to
      those of the Libyan, higher than those of the Nigerian and Indian and lower than
      of the European and American children.

PMID- 7621764
TI  - Effects of calcium ions and atropine on endotoxin-induced contractility deficit
      in rat atrial muscle.
AB  - Isolated atrial muscle preparations obtained from rats injected (ip) with 3.7 x
      10(9) per kg/body weight heat killed pure E. coli (endotoxin) were used to
      investigate the severity of induced mycocardial inotropic dysfunction and the
      effects of some autonotic agents and calcium. Both atrial strips were removed
      from endotoxin-shock rats at 48 and 72 hours post treatment. The control groups
      were given (ip) 0.2ml of isotonic saline and sacrificed at the same period as the
      treated groups. Maximum developed contractile force (amplitude) were
      significantly depressed in atrial strips of shock rats (p < 0.05). Maximum
      deficit in atrial contractility was characterised by altered responsiveness to
      low extra cellular Ca2+ (0.12mM) concentration. Increasing Ca2+ concentration by
      1-3 mM in a normal Ca2+ medium significantly enhanced the contractile force by an
      increase of 88 +/- 5.9% (p < 0.005). Atropine (5 x 10(-7) - 1.5 x 10(-6)M)
      produced positive intropic effect with a maximum increase of 80 +/- 7.1% (p <
      0.05) in the shock atrial strips. Noradrenaline (1 x 10(-7)-10(-6)) on the other
      hand, did not produce any significant inotropic effect. Concomitant
      administration of noradrenaline (1 x 10(-6)M) and atropine (1.5 x 10(-5)M)
      produced positive inotropic effect which is not greater in magnitude compared
      with atropine (5 x 10(-7)M). This study suggests that Ca2+ and atropine may
      provide beneficial effects in endotoxin-induced shock state. It also confirms the
      involvement of myocardium in the pathogenesis of this condition.

PMID- 7621765
TI  - Recurrent intussusception reduced by the patient: a case report.
AB  - A case of recurrent acute intussusception associated with a palpable abdominal
      mass which patient reduces with relief of symptoms is presented. Surgery revealed
      multiple colonic polyps and a total colectomy with ileorectical anastomosis was
      done and the patient has remained well after 3 years of follow up.

PMID- 7621766
TI  - Brain electrical source analysis of laser evoked potentials in response to
      painful trigeminal nerve stimulation.
AB  - Cerebral generators of long latency brain potentials in response to painful heat
      stimuli were identified from potential distributions in 31 EEG leads, using the
      brain electrical source analysis (BESA) programme in the multiple spatio-temporal
      dipole mode. Data were taken from a study with 10 young healthy male subjects who
      participated in 3 identical sessions, 1 week apart, with 4 blocks of 40 stimuli
      (randomized intensities above mean pain threshold). Brief infrared laser heat
      pulses were applied to the right temple; laser evoked brain potentials (LEPs)
      were averaged over 40 stimuli per block. BESA was applied to the grand mean maps
      averaged over the 10 subjects, 3 sessions and 4 stimulus blocks per session, as
      well as to the individual maps. In all cases 4 generators could consistently be
      identified by BESA, which were able to explain up to 98.8% of the total variance
      in scalp distributions at certain time intervals: dipole I with a maximum
      activity at 106.3 msec in the contralateral somatosensory trigeminal cortex, 19.0
      mm beneath the surface; dipole II with a maximum activity at 112.1 msec at the
      corresponding ipsilateral area at a depth of 13.6 mm; dipole III with a maximum
      activity at 130.4 msec in the frontal cortex; dipole IV with 2 relative maximum
      activities at 150.6 and 220.5 msec, localized centrally under the vertex at a
      depth of 33.1 mm, which described both the late vertex negativity and the
      consecutive positivity. BESA applied to the individual LEP maps of each
      individual and session yielded again 4 major generators with sites, strengths and
      orientations comparable to those of the grand mean evaluations. The standard
      deviation (S.D.) of site coordinates within subjects was less than 3 mm for
      dipoles I, II and IV (5 mm for dipole III). The between-subject standard
      deviation was considerably larger (15 mm), which was attributed to individual
      differences in head geometry, size and anatomy. Dipoles I and II are assumed to
      be generators in secondary somatosensory areas of the trigeminal nerve system
      with bilateral representation, though significantly stronger in the contralateral
      site. Dipole III in the frontal cortex may be related to attention and arousal
      processes, as well as to motor cortical initiation for eye movements and muscle
      effects. The central dipole IV describing all late activity between 150 and 220
      msec is probably a representative of perceptual activation and cognitive
      information processing; it was located in deep midline brain structure, e.g., the
      cingular gyrus.

PMID- 7621767
TI  - K-complex evoked in NREM sleep is accompanied by a slow negative potential
      related to cognitive process.
AB  - Evoked cortical responses to two kinds of auditory stimuli (rare and frequent)
      were analyzed to determine whether or not a K-complex evoked in stage 2 of NREM
      sleep is accompanied by some endogenous cognitive components of the event-related
      potential. All the 7 subjects examined in this sleep state failed to provide the
      correct behavioral response to auditory stimuli, but a K-complex was evoked more
      frequently by rare stimuli than by frequent stimuli. EEG segments in stage 2 were
      averaged separately according to the presence or absence of K-complexes emerging
      just after the stimulation. In cases where K-complexes did not emerge, a long
      lasting negative potential of relatively low voltage appeared in the difference
      wave, which was obtained by subtracting the averaged EEG for frequent stimuli
      from that for rare stimuli. In cases where K-complexes emerged, a similar long
      lasting negative potential of large amplitude appeared in the difference wave.
      These data may indicate that a K-complex evoked by an external stimulus is
      accompanied by a potential related to a cognitive process, which appears with
      greater amplitude in cases where a K-complex is evoked.

PMID- 7621768
TI  - EEG monitoring during endovascular embolization of cerebral arteriovenous
      malformations.
AB  - Arteriovenous malformations (AVMs) may have a bad prognosis. Endovascular
      embolization with cyanocrylate represents nowadays an important initial step in a
      staged treatment, that later may include surgery or radiotherapy. Embolization
      may induce significant changes in the dynamics of the cerebral circulation, some
      of which may provoke neurological sequelae. Therefore assessment of potential
      complications is usually done by using a superselective amytal test, during which
      small doses of amytal are injected directly in the pedicle that is going to be
      embolized. In spite of an extensive use of the EEG during endovascular
      embolization its evaluation in terms of benefits and limitations is not
      available. Such evaluation is therefore the aim of this work. EEG monitoring was
      performed during endovascular embolization of 19 patients; a large majority of
      patients presented large AVMs, with Spetzler indexes around IV or V. The main
      results were as follows: (1) EEG changes at baseline were significantly
      correlated with the AVM size and the Spetzler index but were unable to predict
      the difficulties in the embolization; (2) during amytal tests EEG positivity
      reached 35% and consisted mainly in ipsilateral slow focal activity; (3) in some
      cases embolization was performed in spite of transient EEG changes. It was found
      that focal or diffuse abnormalities in the lower frequency range, even when
      slight, could be followed by clinical hazards (3 out of 11 cases); (4) EEG
      monitoring was important in the prediction, evaluation and prognosis of clinical
      complications.

PMID- 7621769
TI  - Topography of auditory evoked long-latency potentials in normal children, with
      particular reference to the N1 component.
AB  - Topographic maps of late auditory evoked potentials were obtained with the Brain
      Atlas III system in 34 healthy, normal hearing children aged 8-16 years. The
      stimulus was a 100 msec, 500 Hz tone burst, presented separately to the left and
      right ears, at 75 dB HL. The resulting auditory evoked potentials showed a
      prominent N1, after about 100 msec, and a topographic map with a corresponding
      fronto-lateral focus designated as the focus of N1 (FN1). Foci with varying
      positions and amplitudes were identified in 33 of 34 subjects after left ear
      stimulation and in 29 of 32 subjects after right ear stimulation. The topography
      showed a high degree of stability in most subjects, with the position of the
      negative "peak" of FN1 in front of the interaural line and with a dominance
      contralateral to the ear stimulated. There was a significant decrease in the
      latency of N1 with increasing age. FN1 tended to change position with age and
      some differences from adults were also observed. In conclusion, a distinct
      topographic pattern of the N1 component of the late auditory evoked potentials
      was seen in the majority of children. It remains to be established to what extent
      this method may be clinically useful for disclosing functional disturbances in
      the central auditory pathways.

PMID- 7621770
TI  - Auditory brain-stem responses and MRI findings in patients with olivo-ponto
      cerebellar (Dejerine-Thomas)-type and cerebello-olivary (Holmes)-type spino
      cerebellar degeneration.
AB  - Auditory brain-stem responses (ABRs) and magnetic resonance imaging (MRI)
      findings were investigated in 10 patients with olivo-ponto-cerebellar atrophy
      (OPCA: Dejerine-Thomas type) and in 5 patients with Holmes-type cerebello-olivary
      degeneration. In patients with OPCA, (1) the III-V interpeak latency (IPL) was
      shortened significantly (P < 0.05) as compared with normal subjects when the
      decrease in longitudinal distance of the pons was within 20% of that of normal
      controls, (2) the I-III IPL was elongated (P < 0.05), the III-V IPL was shortened
      (P < 0.01), and the amplitude of the V wave was reduced (P < 0.05) when the
      decrease in longitudinal distance of the pons was more than 20% of that of normal
      controls. Patients with Holmes-type degeneration showed no significant difference
      in any component of ABRs or in the size of any part of the brain-stem, as
      compared with normal subjects. We conclude that abnormalities in the I-III IPL or
      the III-V IPL in patients with OPCA were produced by changes in the volume
      conduction in the pons and midbrain. This study also suggests that differences of
      IPL appear between OPCA and Holmes-type degeneration.

PMID- 7621771
TI  - Automatic auditory discrimination is impaired in Parkinson's disease.
AB  - Deviant tones embedded in a sequence of standard tones elicit an event-related
      potential (ERP) component called the mismatch negativity (MMN), which reflects
      automatic stimulus change detection in the human auditory system. To determine
      whether stimulus change detection is impaired in Parkinson's disease (PD), we
      recorded ERPs in 13 non-demented patients with PD and in 11 age-matched healthy
      control subjects both when tones were attended and when they were unattended. The
      difference area between deviant and standard ERPs was used to evaluate the MMN in
      the 'unattended' condition. The MMN was significantly smaller in patients with PD
      than in controls. In the attended condition, the amplitudes of both N1 and the N2
      complex were smaller in the patient group than in controls. MMN attenuation
      suggests that PD patients have impaired automatic stimulus change detection
      compared with healthy controls. This might be caused by dopamine deficiency in
      PD.

PMID- 7621772
TI  - Alterations of intrahippocampal cognitive potentials in temporal lobe epilepsy.
AB  - During presurgical evaluation event-related potentials were recorded with depth
      electrodes located longitudinally within the hippocampus in 25 patients suffering
      from unilateral temporal lobe epilepsy. Rare stimuli in a visual oddball paradigm
      elicited a pronounced negativity ("NO") in the hippocampal body. Amplitudes were
      significantly reduced on the side of the primary epileptogenic area. Visual
      presentations of words in a recognition paradigm evoked an earlier negativity
      ("ENW") in anterior and a later negativity ("LNW") in posterior hippocampal
      structures. Both were sensitive for recognition effects and showed reduced
      amplitudes on the side of the primary epileptogenic area. Relating the
      differences of left and right hippocampal "NO" and "ENW" amplitudes proved to be
      a sensitive method for topological diagnosis and allowed a correct lateralization
      of the primary epileptogenic area in all patients. Amplitudes of the hippocampal
      ENW, evoked in the dominant hemisphere by first presentations, strongly
      correlated with the recognition rate, when the primary epileptogenic area was
      situated in the contralateral temporal lobe. This correlation was reduced by the
      presence of ipsilateral epileptogenic foci.

PMID- 7621773
TI  - Effect of unilateral claustral lesion on intermittent light stimulation-induced
      convulsive response in D,L-allylglycine treated cats.
AB  - The effect of unilateral lesions of the claustrum was examined in cats treated
      with D,L-allylglycine. Prior to the lesion, intermittent light stimulation (ILS)
      induced (a) myoclonic jerking associated with generalized spike, or polyspike and
      wave discharge, maximal in the subcortical structures monitored and the cortical
      visual area, and (b) bisymmetrical generalized-onset tonic-clonic convulsions
      associated with sustained spike discharge in the motor cortex bilaterally.
      Subsequent to a unilateral lesion of the claustrum, ILS-induced electro-clinical
      manifestations of myoclonic jerking remained unchanged. However, the
      bisymmetrical convulsive pattern transformed into a partial onset secondarily
      generalized convulsive pattern beginning in the intact hemisphere. It is
      concluded that the claustrum plays an important role for access of visual
      afferents to the motor mechanism responsible for ILS-induced convulsive seizure.

PMID- 7621774
TI  - Differential effects of ozone on lung epithelial lining fluid volume and protein
      content.
AB  - Urea dilution has been used to estimate the volume of epithelial lining fluid
      (ELF) in the respiratory tract. However, ELF volume may be overestimated as the
      result of rapid net diffusion of urea from tissues into the bronchoalveolar
      lavage (BAL) fluid. This study established a protocol for rat BAL in a manner
      that minimizes this problem and then used this procedure to examine the
      edemagenic effects of ozone (O3) exposure on ELF volume and the concentrations of
      ELF protein and albumin. One passage lavage with variable dwell times up to 30 s
      showed no difference in recovered urea, protein, and albumin and ELF volume
      between 0 and 4 s, but a progressive increase of each thereafter. The calculated
      concentrations of protein and albumin in ELF did not vary significantly with
      dwell time. By increasing the number of lavage passages from one to three, the
      amounts of recovered urea, protein, and albumin and estimated ELF volume were
      increased with each passage. Again, the calculated concentrations of protein and
      albumin in ELF did not vary appreciably. When a single lavage passage and no
      added dwell time were used, it was observed that exposure of rats to 2 but not
      0.5 and 1 ppm O3 increased urea, protein, and albumin in the BAL immediately
      after 6 h exposure. In addition, at 18 h postexposure to 1 ppm O3, ELF volume
      increased only 21%, but protein and albumin concentrations in ELF were 2.3- and
      4.5-fold of control values, respectively. A higher O3 concentration (2 ppm)
      moderately increased ELF volume (+83%) and exerted even greater effects on
      concentrations of ELF protein (7.8-fold) and albumin (19-fold) while lower O3
      dosage (0.5 ppm) had no significant effect. SDS-PAGE analysis showed that small
      serum proteins including albumin were greatly enriched in lung BAL fluid of 1 ppm
      O3-exposed rats. These results demonstrate that movement of water and protein
      into the airspaces after O3 exposure is not strictly coupled, and that protein
      recovery by BAL should cautiously be used to indicate airspace edema as a result
      of O3 injury.

PMID- 7621775
TI  - Primary plexogenic pulmonary hypertension shows imperfect formation of the
      internal elastic lamina of the pulmonary arteries.
AB  - Lung tissue from subjects dying from primary plexogenic pulmonary hypertension
      (PPH) has shown defects of elastin formation of the lung arteries. Lung vessels
      from 5 cases of PPH were compared with those of 9 age-matched normal subjects,
      and 24 individuals having secondary pulmonary hypertension (2 degrees PH). PPH
      cases and those with 2 degrees PH due to congenital heart disease with left-to
      right shunts (2 degrees PH, LRS), showed active proliferation of medial smooth
      muscle cells (SMC) through defects of the internal elastic lamina (IEL) into the
      arterial lumen to form typical plexiform lesions. Larger arteries showed
      accelerated intimal thickening similar to normal aging. Plexiform lesions were
      not seen in normal subjects or in those developing high pulmonary pressures later
      in life. The observations showed that the development of discontinuities of the
      IEL of the pulmonary arteries and intimal thickening is accelerated in normal
      subjects by high pulmonary artery pressure, especially when this is established
      at a very young age. They suggest that such discontinuities occur in PPH due to
      inherent abnormality of the elastin of the arterial walls, with advanced early
      proliferation of medial SMC and obstruction of the pulmonary arterial
      circulation.

PMID- 7621777
TI  - Purification of murine pulmonary type II cells for flow cytometric cell cycle
      analysis.
AB  - Mice are widely used as animal models for in vivo lung disease. Despite this
      fact, few methods exist for isolation of type II pneumocytes from mouse lung,
      limiting the study of alveolar epithelial characteristics in these models. This
      study investigated several methods for labeling murine lung cell suspensions for
      flow cytometric identification and sorting of type II pneumocytes. Crude lung
      cell suspensions were prepared after intratracheal instillation of Dispase and
      were labeled using phosphine alone or in combination with Helix pomatia lectin,
      Maclura pomifera lectin, or anti-murine-CD32. Crude cell suspensions yielded 17.4
      million cells per animal with 19.5% type II pneumocytes by Pap staining.
      Ultrastructural evaluation of the sorted cell pellets (1-1.5 million cells each)
      demonstrated optimal type II cell purity in preparations labeled with phosphine
      and anti-CD32 (94.3% type II cells, 0.4% macrophages, 2.8% Clara cells, and 2.5%
      other). Nuclear suspensions appropriate for cell cycle analysis were produced by
      sorting the type II cells directly into hypotonic propidium iodide, and these
      preparations clearly demonstrated a substantial increase in S-phase type II cells
      during proliferative repair of BHT-induced acute lung injury.

PMID- 7621778
TI  - Modulation of airspace enlargement in elastase-induced emphysema by intratracheal
      instillment of hyaluronidase and hyaluronic acid.
AB  - The study examined how lung hyaluronic acid content influences airspace
      enlargement in elastase-induced emphysema. To determine the effect of a decrease
      in hyaluronic acid, hamsters received a single intratracheal instillment of
      hyaluronidase 24 h prior to administration of pancreatic elastase by the same
      route. One week later, these animals showed significantly greater airspace
      enlargement than controls sequentially instilled with saline and elastase (128
      vs. 100 microns; p < .05). Conversely, intratracheal administration of hyaluronic
      acid immediately after elastase instillment resulted in a marked decrease in
      airspace enlargement at 1 week compared to controls receiving elastase followed
      by saline (82 vs. 122 microns; p = .005). Since hyaluronic acid has no elastase
      inhibitory capacity, its effect may involve extracellular matrix interactions not
      directly related to elastic fiber breakdown. This concept is supported by the
      finding that animals treated with hyaluronidase and elastase showed no greater
      loss of lung elastin than that observed in the saline/elastase control group,
      despite demonstrating a marked increase in airspace enlargement. Further work is
      needed to determine how hyaluronic acid influences airspace enlargement and to
      evaluate the potential use of this substance as a treatment for emphysema.

PMID- 7621776
TI  - Developmental differences in production of lipoxygenase metabolites by ovine
      lungs.
AB  - This study determined age-related differences in production of lipoxygenase
      metabolites by ovine lungs. Lungs of near-term fetal (146 +/- 2 days gestation),
      neonatal (8 +/- 2 days), and adult sheep were homogenized and 9000g fraction
      (9000g) cytosol, and microsomes were prepared by differential centrifugation.
      These subcellular fractions were incubated for 10 min at 37 degrees C, either
      alone, with [14C]arachidonic acid ([14C]AA), or with A23187.
      Hydroxyeicosatetraenoic acids (HETEs) and leukotrienes (LTs) were extracted from
      incubation media and quantitated by HPLC. All three lung subcellular fractions
      metabolized [14C]AA into 5-, 12-, and 15-HETEs. Production of each HETE was
      greater in neonatal and adult 9000g and microsomes than in fetal microsomes.
      Leukotriene production from [14C]AA by 9000g, cytosol, and microsomes was
      greater, the older the animal. Production of LTs by microsomes was greater than
      that by cytosol at all ages. LT production from endogenous AA increased
      significantly on stimulation with 5 microM A23187, and was inhibited by 50 microM
      NDGA. In each case, LTC4 was metabolized to LTD4 and LTE4. The data show that
      ovine lungs metabolize exogenous and endogenous AA into 5-, 12-, and 15-HETEs and
      LTs and that production of lipoxygenase metabolites by the lung increases with
      age. Also, in the ovine lung, 5-lipoxygenase is more membrane bound than
      cytosolic.

PMID- 7621779
TI  - Myoendothelial junctional complexes in postobstructive pulmonary vasculopathy: a
      quantitative electron microscopic study.
AB  - Postobstructive pulmonary vasculopathy (POPV), produced by chronic unilateral
      ligation of one pulmonary artery, is characterized by (1) marked proliferation of
      bronchial collateral vessels, (2) increased pulmonary vascular resistance, and
      (3) hyperreactivity of arteries to serotonin and of veins to histamine. Electron
      microscopic examination of the vessels in POPV suggested an increase in
      myoendothelial junctional complexes (MEJC). To quantitate this change, the number
      of MEJC in the vessel walls of the left lung was compared with that of the right
      lung in 16 dogs after ligation of the left main pulmonary artery for 8.4 +/- 1.6
      (SE) months. The lungs were fixed by airway instillation of 3% glutaraldehyde.
      Electron micrographs were taken of pulmonary arteries, capillaries, and veins and
      of bronchial vessels, and their external diameter and length of endothelial basal
      lamina were measured. The MEJC were counted and expressed as number per length of
      basal lamina and typed: Type I consisted of endothelial processes, type II of
      smooth muscle or pericyte processes, and type III of processes from each cell
      type. The results demonstrated that the vasculature from the control lung had the
      smallest number of MEJC and the majority were type I. With ligation, there was a
      significant increase (p < .01) in the number of MEJC for each type of vessel
      examined, but no significant change in the distribution of the type. In addition,
      no correlation was found between the number of MEJC and vascular diameter. It can
      be concluded that MEJC are increased in each region of the lung's vasculature in
      POPV and that they may play a role in the proliferative response of the bronchial
      vasculature, the remodeling of the pulmonary vasculature, and the pulmonary
      vascular hyperreactivity of this model.

PMID- 7621780
TI  - Characterization of endothelin receptor subtypes on airway smooth muscle cells.
AB  - Endothelin-1 (ET-1) has constrictor and mitogenic effects on airway smooth muscle
      strips and cultured cells, respectively. This study addresses the type of the ET
      receptor subtype(s) present on ovine airway smooth muscle cells and the
      possibility of autocrine effects. The expression of the preproendothelin-1 gene
      was demonstrated by Northern analysis, and the medium obtained from these cells
      contained immunoreactive-ET-1. Competitive binding experiments between [125I]ET-1
      and ET-1, ET-3, and two ET-receptor subtype selective-ligands, BQ-123 (ETA) and
      sarafotoxin S6c (ETB), yielded IC50 values of 1.1 +/- 0.1, 227 +/- 13, 12 +/- 1,
      and 194 +/- 21 nM, respectively. ET-3 also gave a limited number of higher
      affinity sites. In the presence of BQ-123 (1 microM), the binding of [125I]ET-1
      was decreased by 80-85%, and the IC50 values with ET-1, ET-3, and S6c were 2.0 +/
      0.4, 3.6 +/- 0.6, and 1.1 +/- 0.9 nM, respectively. In similar experiments with
      0.1 microM sarafotoxin S6c, the respective IC50 values for ET-1 and ET-3 were 2.4
      +/- 0.4 and 300 +/- 20 nM. These results demonstrate that about 85 +/- 5% of ET-1
      binding to airway smooth muscle cells is to ETA receptors and that these cells
      produce ET-1 in vitro.

PMID- 7621781
TI  - Release of a mitogenic factor by adult rat lung slices in culture.
AB  - In an effort to develop a suitable bioassay for testing lung growth factors that
      might be operative during compensatory lung growth following partial
      pneumonectomy, a simple and inexpensive lung organ culture system was
      characterized. The culture employs lung tissue slices obtained by means of a
      device allowing thicknesses of 500 microns to be cut reproducibly. To avoid the
      collapse of the organ, the alveolar spaces were filled prior to culture with
      Noble agar-containing Eagle's-Dulbecco's modified medium. Lung tissue sections
      could be maintained ultrastructurally intact for at least one week. The results
      showed that upon culture, a part of the type II pneumocytes undergo
      differentiation into type I pneumocytes, thus demonstrating that the culture
      system may be suited for differentiation studies. One surprising feature of this
      culture system was the mitogenic impulse associated with culture. Radioactively
      labeled thymidine incorporation was strongly stimulated in the culture, mainly
      affecting the epithelial cells, as could be established by "back-to-back"
      autoradiography. With a reconstruction experiment, it was possible to demonstrate
      the local release of a mitogenic factor following slicing, mincing, or dissection
      of the lung tissue, which could be assayed by its ability to induce serum-starved
      Balb/c 3T3 cells to synthesize DNA in culture.

PMID- 7621782
TI  - [Medical attention at full speed].

PMID- 7621784
TI  - [Barriers that protect lives].

PMID- 7621783
TI  - [Sterrad, choice for the future].

PMID- 7621785
TI  - [Angels with clown faces].

PMID- 7621786
TI  - [The hour of change].

PMID- 7621787
TI  - Joint United States--Mexico Conference on Fate, Transport, and Interactions of
      Metals. Proceedings. Tucson, Arizona, April 13-16, 1993.

PMID- 7621790
TI  - Metal speciation in environmental and biological systems.
AB  - Metal ions form complexes with naturally occurring complexing agents or ligands
      released from industrial activity. The metal complexes are thereby mobilized and
      transported in environmental and biological systems. The impact of such metal
      complexes depends on the metal complex species that are kinetically and
      thermodynamically stable in these homogeneous and heterogeneous systems. The
      distribution of metal complex species in these complex systems can be calculated
      from available formation constant data. This article describes the importance of
      verifying the validity of these calculations by employing experimental techniques
      that can speciate metal complexes.

PMID- 7621788
TI  - Bone lead measured by X-ray fluorescence: epidemiologic methods.
AB  - In vivo X-ray fluorescence (XRF) measurement of bone lead concentration (XRF) has
      emerged as an important technique for future epidemiological studies of long-term
      toxicity. Several issues germane to epidemiologic methodology need to be
      addressed, however. First, sources of variability in measurements of bone lead
      need to be quantified, including imprecision related to the physical measurement
      itself and the variability of lead deposition over the two main compartments of
      bones (cortical vs. trabecular) and within each compartment. Imprecision related
      to the physical measurement can be estimated for each individual measurement
      based on the variability of the signal and background. Second, approaches to low
      level data need to be debated. We argue for using the minimal detection limit
      (MDL) to compare instruments and interpret individual measurements; however, with
      regard to epidemiologic studies, we would abandon the MDL in favor of using all
      point estimates. In analyses using bone lead as an independent variable,
      statistical techniques can be used to adjust regression estimates based on
      estimates of measurement uncertainty and bone lead variability. Third, factors
      that can be expected to modify the relationship between bone lead and toxicity
      such as gravida history, endocrinological states, nutrition, and other important
      influences on bone metabolism, need to be identified and measured in
      epidemiologic studies. By addressing these issues, investigators will be able to
      maximize the utility of XRF measurements in environmental epidemiologic studies.

PMID- 7621791
TI  - Oxidation-reduction reactions of metal ions.
AB  - Several metal or metalloid ions exist in multiple oxidation states and can
      undergo electron transfer reactions that are important in biological and
      environmental systems. There are endogenous metal ions such as iron, copper, and
      cobalt that participate in oxidation-reduction reactions with species of oxygen
      like molecular dioxygen, superoxide, and hydrogen peroxide. These reactions may
      be modulated by endogenous reducing agents such as glutathione, ascorbate, and
      tocopherol. The reactions can be described in terms of thermodynamics through the
      use of standard electrode potentials. A favorable reaction will depend on the
      concentrations of the reactants and may depend on the pH and/or on the presence
      of organic ligands that form complexes with the metal or metalloid. Arsenate
      (As(V)) can react with glutathione in buffered aqueous solutions to produce
      arsenite (As(III)) and oxidized glutathione. This reaction may be important in
      the methylation reactions of arsenic. Arsenic species can decrease the red blood
      cell levels of reduced glutathione, but the products of oxidation and the
      mechanism of oxidation are more complex than those found in water alone. Chromium
      (VI) is thought to interact with DNA after first reacting with a reducing agent
      such as glutathione to form lower oxidation states of chromium. These examples
      illustrate the importance of oxidation-reduction reactions for toxic metals and
      metalloids.

PMID- 7621789
TI  - Genotoxic monitoring of workers at a hazardous waste disposal site in Mexico.
AB  - Chromosomal aberration and sister chromatid exchange (SCE) frequencies were
      determined in lymphocytes cultured from 12 high-risk individuals working at a
      landfill for hazardous waste disposal. Cell proliferation kinetics (CPK) was also
      determined. Compared with 7 control individuals, no effects were observed with
      respect to SCE nor on CPK. However, the workers exhibited significantly higher
      frequencies of chromatid and chromosomal deletions, the magnitude of which was
      related with exposure time. This study suggests that when high-risk exposure is
      suspected, determining biomarkers of genotoxic damage (e.g., chromosomal
      aberrations), is useful for risk assessments.

PMID- 7621792
TI  - Trace metals speciation by HPLC with plasma source mass spectrometry detection.
AB  - The analysis of environmental and biological samples often requires detection at
      the parts per billion (ppb) level. Plasma source mass spectrometry has potential
      as a method for the analysis and speciation of trace elements. This is due to the
      technique's highly selective nature and excellent sensitivity. In comparison to
      atomic emission detection, detection limits are usually two to three orders of
      magnitude lower for plasma MS determinations. Interfacing HPLC with plasma MS
      provides a means of separation that is necessary for speciation. Speciation
      involves the determination and quantitation of the various chemical forms of a
      particular element. A host of HPLC-ICP-MS techniques may be used to obtain this
      information. This brief report will focus on the most recent work in this area,
      with emphasis on the work done in our laboratory.

PMID- 7621794
TI  - Competitive complexation of trace metals with dissolved humic acid.
AB  - In this study we investigated the effects of competing trace metals and Ca2+ on
      Cd(II), Pb(II), and Cu(II) complexation by humic acid extracted from groundwater
      in Orange County, California. Two types of titration experiments were conducted,
      those using a single metal and those in which the humic acid had been
      preequilibrated with a competing metal (either a trace metal or Ca2+). The labile
      metal concentration in the titration was determined by differential pulse
      polarography (DPP). Results show the different effects of competing trace metal
      ions and the effect of Ca2+. Both trace metals and Ca2+ do not compete
      effectively with Cd(II) complexation. While no effects of Cu(II) on Pb(II)
      complexation were observed, the presence of Cd(II) appeared to slightly enhance
      the binding between Pb(II) and humic acid. The addition of Pb(II) decreased the
      amount of Cu(II) complexation, but Cd(II) caused a slight increase at the lower
      concentrations. Calcium, however, decreased the amount of complexation for all
      three metals. Results indicate that the metals are not necessarily competing for
      the same sites. Conformational changes that occur when trace metals bind to the
      different sites may cause this competing or enhanced effect. Since Ca(II) is
      introduced at two orders of magnitude higher in concentration than the trace
      metals, it can outcompete the trace metal for sites where electrostatic
      interactions dominate. The results indicate that in groundwater situations, where
      more than one metal is present, the effect of other metals must be considered in
      predicting metal speciation.

PMID- 7621793
TI  - Toxic metals in aquatic ecosystems: a microbiological perspective.
AB  - Microbe-metal interactions in aquatic environments and their exact role in
      transport and transformations of toxic metals are poorly understood. This paper
      will briefly review our understanding of these interactions. Ongoing research in
      Lake Chapala, Mexico, the major water source for the City of Guadalajara,
      provides an opportunity to study the microbiological aspects of metal-cycling in
      the water column. Constant resuspension of sediments provides a microbiologically
      rich aggregate-based system. Data indicate that toxic metals are concentrated on
      aggregate material and bioaccumulate in the food chain. A provisional model is
      presented for involvement of microbial aggregates in metal-cycling in Lake
      Chapala.

PMID- 7621795
TI  - The NIEHS Superfund Basic Research Program: overview and areas of future research
      directions.
AB  - The National Institute of Environmental Health Sciences' Superfund Basic Research
      Program is currently funding 142 separate research projects within 18 programs
      encompassing 29 universities and institutions around the United States. The
      research under this program covers a wide range of interdisciplinary science from
      both the biomedical and nonbiomedical perspectives. This is a unique program of
      technology-driven research. Nonetheless, there are some areas of research that
      should be investigated or investigated further, should funds become available.
      Environmental health risk posed by the location of Superfund sites may be
      distributed inequitably across socioeconomic status and racial groups. Since one
      in five children now lives below the poverty line, an important aspect of
      environmental equity must be the investigation of the health effects of
      environmental factors on children. The multidisciplinary investigation of the
      effects of hazardous substance exposure on children is an area that needs much
      research due to the fact that most of the toxicologic data available are based on
      adults and animals. This program is funding 27 projects on ecologic damage posed
      by hazardous wastes. Much more research is needed in the investigation of toxic
      effects on natural succession of ecosystems as well as on their effects on
      biodiversity to further our understanding of the food web in the role of
      bioavailability in human health, and to examine the bioaccumulation of these
      chemicals as it relates to their fate and transport. This program is researching
      and developing many innovative technologies for detecting, assessing, and
      reducing toxic materials in the environment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7621796
TI  - Metals in some lagoons of Mexico.
AB  - The concentrations of metals, Cd, Cu, Fe, Mn, Ni, Pb, and Zn were determined in
      some lagoons to establish the level of metal pollution. The lagoons studied were
      Alvarado lagoon, Veracruz; San Andres lagoon, Tamaulipas; and Terminos lagoon,
      Campeche. The concentrations were determined in water, oyster (Crassostrea
      virginica), and sediments. Metals were accumulated in either oysters or
      sediments. Cu and Zn were higher in oysters and Fe and Mn were higher in
      sediments. The results in water samples were compared with the limit established
      by the Secretaria de Ecologia and Desarrollo Urbano Report and briefly discussed.

PMID- 7621797
TI  - Movement and distribution of arsenic in the Aberjona watershed.
AB  - The distribution and movement of arsenic was investigated on the Aberjona
      watershed in eastern Massachusetts for the purpose of identifying where and by
      what processes present and past human exposures to this element could have
      occurred. It was found that although most of the arsenic was originally released
      in the headwaters of the watershed, extensive migration had occurred, and the
      potential for human exposure existed far from designated hazardous waste sites.
      Both surface water and groundwater were found to be important transport pathways;
      arsenic moved between these two media at several locations in the watershed, with
      hydrology and concomitant redox, sorption, and alkylation processes determining
      the observed patterns of arsenic movement. These findings demonstrate that risk
      assessments or remedial investigations restricted to designated sites or
      properties in a watershed may yield both an inaccurate picture of the overall
      risks presented by a chemical and a less-than-optimum focus for remedial efforts.
      Since total recovery of the arsenic on this watershed is probably not feasible,
      cost-effective management will also depend on an adequate understanding of
      arsenic biogeochemistry and hydrologic transport processes at the watershed
      scale. Because the Aberjona Watershed is typical of many urban, industrialized
      areas, these results suggest that the whole watershed often defines the
      appropriate unit for investigation of chemical contamination in the environment.

PMID- 7621798
TI  - Modeling of natural organic matter transport processes in groundwater.
AB  - A forced-gradient tracer test was conducted at the Georgetown site to study the
      transport of natural organic matter (NOM) in groundwater. In particular, the goal
      of this experiment was to investigate the interactions between NOM and the
      aquifer matrix. A detailed three-dimensional characterization of the hydrologic
      conductivity heterogeneity of the site was obtained using slug tests. The
      transport of a conservative tracer (chloride) was successfully reproduced using
      these conductivity data. Despite the good simulation of the flow field, NOM
      breakthrough curves could not be reproduced using a two-site sorption model with
      spatially constant parameters. Preliminary results suggest that different
      mechanisms for the adsorption/desorption processes, as well as their spatial
      variability, may significantly affect the transport and fate of NOM.

PMID- 7621799
TI  - Environmental exposure to chromium compounds in the valley of Leon, Mexico.
AB  - The effects on the environment and health of the operation of a chromate
      compounds factory and tanneries in the Leon valley in central Mexico are
      discussed. Sampling and analysis of chromium were performed in water, soil, and
      human urine. Groundwater has been polluted in an area of about 5 km2 by the
      leaching of a solid factory waste, which results in concentrations up to 50 mg/l
      of hexavalent chromium. The plume shape and extension appear to be controlled by
      the prevailing well extraction regime. Total chromium was detected in the soil
      around the factory as a result of both aerial transport and deposition of dust
      produced in the chromate process and irrigation with tannery-contaminated water.
      Analysis of the impact of chromium in air and water on populations with various
      degrees of exposure revealed that highly harmful health effects were not
      observed.

PMID- 7621801
TI  - Biosurfactant-facilitated remediation of metal-contaminated soils.
AB  - Bioremediation of metal-contaminated wastestreams has been successfully
      demonstrated. Normally, whole cells or microbial exopolymers are used to
      concentrate and/or precipitate metals in the wastestream to aid in metal removal.
      Analogous remediation of metal-contaminated soils is more complex because
      microbial cells or large exopolymers do not move freely through the soil. The use
      of microbially produced surfactants (biosurfactants) is an alternative with
      potential for remediation of metal-contaminated soils. The distinct advantage of
      biosurfactants over whole cells or exopolymers is their small size, generally
      biosurfactant molecular weights are less than 1500. A second advantage is that
      biosurfactants have a wide variety of chemical structures that may show different
      metal selectivities and thus, metal removal efficiencies. A review of the
      literature shows that complexation capacities of several bacterial exopolymers
      was similar to the complexation capacity of a rhamnolipid biosurfactant produced
      by Pseudomonas aeruginosa ATCC 9027.

PMID- 7621800
TI  - Trace metal mobilization in soil by bacterial polymers.
AB  - Enhanced transport of trace metal in porous media can occur in the presence of a
      ligand or "carrier" that has a high affinity for binding the pollutant, is
      dispersed and mobile in the soil environment, is recalcitrant with respect to
      microbial degradation, and is acceptable to the public. These aspects of the
      facilitated transport to trace metals are discussed with respect to a naturally
      occurring carrier: extracellular polymers of bacterial origin. The literature is
      reviewed regarding the production and composition of bacterial extracellular
      polymers, the processes relevant to the facilitated transport of trace metals in
      soil by bacterial polymers, and potential for transformation of polymers in soils
      by microbial degradation. Model calculations of contaminant retardation are
      presented for the case of polymer-mediated transport of cadmium in a sandy
      aquifer material. The available information suggests that extracellular polymers
      can bind metal ions and are mobile in the soil environment. Extracellular
      polymers also appear to be relatively slowly degraded by soil microorganisms.
      These properties and the supporting model calculations indicate that
      extracellular polymers of bacterial origin merit consideration as agents that may
      be applied to contaminated soils to enhance trace metal mobility.

PMID- 7621802
TI  - A pilot plant for removing chromium from residual water of tanneries.
AB  - The purpose of this study is to develop a technical process for removing
      trivalent chromium from tannery wastewater via precipitation. This process can be
      considered an alternative that avoids a remediation procedure against the metal
      presence in industrial wastes. This process was verified in a treatment pilot
      plant located in Leon, Mexico handling 10 m3/day of three types of effluents. The
      effluent streams were separated to facilitate the elimination of pollutants from
      each one. The process was based on in situ treatment and recycle to reduce
      problems associated with transportation and confinement of contaminated sludges.
      Two types of treatment were carried out in the pilot plant: The physical/chemical
      and biological treatments. Thirty-five experiments were conducted and the studied
      variables were the pH, type of flocculant, and its dose. The statistical
      significance of chromium samples was 94.7% for its precipitation and 99.7% for
      recovery. The objectives established for this phase of the development were
      accomplished and the overall efficiencies were measured for each stage in the
      pilot plant. The results were: a) chromium precipitation 99.5% from wastewater
      stream, b) chromium recovery 99% for recycling, and c) physical/chemical
      treatment to eliminate grease and fat at least 85% and 65 to 70% for the
      biological treatment. The tanning of a hide lot (350 pieces) was accomplished
      using 60% treated and recycled water without affecting the product quality. The
      recovered chromium liquor was also used in this hide tanning. This technical
      procedure is also applicable for removing heavy metals in other industrial
      sectors as well as in reducing water consumption rates, if pertinent adjustments
      are implemented.

PMID- 7621803
TI  - Evaluation of the nephrotoxicity of complex mixtures containing organics and
      metals: advantages and disadvantages of the use of real-world complex mixtures.
AB  - As part of a multidisciplinary health effects study, the nephrotoxicity of
      complex industrial waste mixtures was assessed. Adult, male Fischer 344 rats were
      gavaged with samples of complex industrial waste and nephrotoxicity evaluated 24
      hr later. Of the 10 tested samples, 4 produced increased absolute or relative
      kidney weight, or both, coupled with a statistically significant alteration in at
      least one of the measured serum parameters (urea nitrogen (BUN), creatinine
      (CREAT), and BUN/CREAT ratio). Although the waste samples had been analyzed for a
      number of organic chemicals and 7 of the 10 samples were analyzed also for 12
      elemental metals and metalloids, their nephrotoxicity was not readily predicted
      from the partial chemical characterization data. Because the chemical form or
      speciation of the metals was unknown, it was not possible to estimate their
      contribution to the observed biological response. Various experimental
      approaches, including use of real-world complex mixtures, chemically defined
      synthetic mixtures, and simple mixtures, will be necessary to adequately
      determine the potential human health risk from exposure to complex chemical
      mixtures.

PMID- 7621804
TI  - Fate, transport, and interactions of heavy metals.
AB  - Mishandling of hazardous wastes, like their unauthorized disposal in abandoned
      dump yards or sites, in river beds, estuaries or in the sea, causes substantial
      damage to the environment and its resources and, given the persistence and
      toxicity of these pollutants, they can seriously damage human health and quality
      of life. The importance of controlling management, transport, and disposal of
      toxic and hazardous substances in the years to come will be a crucial issue in
      the design and implementation of public policies. This is especially true for
      residents of such areas as the border between the United States and Mexico, where
      historically hazardous wastes have been a public health and environmental
      problem. The aim of this Conference on the Fate, Transport, and Interactions of
      Metals, A Joint United States-Mexico Conference, co-sponsored by the National
      Institute of Environmental Health Sciences, Superfund Basic Research Program, the
      National University of Mexico, Program for the Environment and the Pan American
      Health Organization, and hosted by the University of Arizona Center for
      Toxicology, College of Pharmacy, is to begin a joint effort by the United States
      and Mexico to better understand the complex problems related to heavy metals as
      hazardous wastes.

PMID- 7621805
TI  - Metal transport in cells: cadmium uptake by rat hepatocytes and renal cortical
      epithelial cells.
AB  - The toxic metals appear to use the transport pathways that exist for biologically
      essential metals. In this regard interactions between the toxic and essential
      metals are possible. This report summarizes recent findings on the transport of
      cadmium in rat hepatocytes and renal cortical epithelial cells in the presence or
      absence of certain essential metals. The transport of cadmium in hepatocytes does
      not require energy and, therefore, is not an active process. It occurs primarily
      (80%) by temperature-sensitive processes, i.e., ion channels and carriers, that
      involve interaction with sulfhydryl groups. These processes apparently exist for
      the transport of essential metals like copper, zinc and calcium. The remaining
      20% of the cadmium in hepatocytes is transported via a temperature-insensitive
      process, possibly by diffusion. In comparison with the hepatocytes, a smaller
      fraction (30%) of the cadmium transport through the basolateral membrane and none
      from the apical membrane of the renal cortical epithelial cells is temperature
      sensitive. Total accumulation through the basolateral membrane is about twice
      that through the apical membrane. A majority of the cadmium transport in the
      renal cells is by diffusion. As in hepatocytes, copper, zinc and mercury
      antagonize cadmium transport through the apical membranes of the renal cells. The
      relative antagonism by copper is the same (25%); however, the antagonism by zinc
      (16%) and mercury (10%) is 4- to 6-fold lower than in hepatocytes. It appears
      that the relative contribution of various transport pathways available for
      cadmium uptake is different in each cell type and apparently depends on the
      morphological and functional differences between the cell membranes.

PMID- 7621806
TI  - Interaction of metals during their uptake and accumulation in rabbit renal
      cortical slices.
AB  - The uptake and accumulation of metals occurs in the kidney, which is a key site
      for interaction between metal nephrotoxicants. The uptake/accumulation and
      interaction of CdCl2, HgCl2, K2Cr2O7, and NaAsO2 was examined in precision-cut
      rabbit renal cortical slices. Slices were incubated with 10(-6) to 10(-3) M of a
      single metal toxicant or combinations of metal toxicants for 12 hr in DME-F12
      media. Slices were blotted and sandwiched between two mylar films stretched
      across XRF sample cups. Quantitation of the metal in the slices was performed by
      proton-induced X-ray emission analysis (PIXE). The uptake of the metals was
      rapid, often reaching a maximum between 3 to 6 hr; the accumulation of Hg was
      highest, followed in order by Cd, Cr, and As. When two metals were present
      together, substantial alterations were observed in the uptake of the metals in
      the slices. HgCl2 hindered the uptake of K2Cr2O7, NaAsO2, CdCl2 (in this order),
      whereas these metals facilitated the uptake of HgCl2. However, a decreased uptake
      of both metals was often noted after exposure to other combinations of metals.
      PIXE analysis of metal content in slices is attractive since all elements (atomic
      number > 20) can be determined simultaneously. This information will be
      particularly useful in studying potential toxic interactions.

PMID- 7621807
TI  - Glutathione effects on toxicity and uptake of mercuric chloride and sodium
      arsenite in rabbit renal cortical slices.
AB  - The mechanism of renal uptake of nephrotoxic heavy metals such as HgCl2 and
      NaAsO2 is not clear. The metals are known to react with endogenous sulfhydryls
      such as glutathione (GSH), so metal-GSH conjugates may be delivered to the
      kidney. To study this possibility, renal cortical slices from male New Zealand
      white rabbits were incubated with 10(-4) M HgCl2 or 10(-3) M NaAsO2 +/-
      stoichiometric amounts (1-3x) of GSH; or synthetic metal-GSH conjugates [10(-4) M
      Hg(SG)2 or 10(-3) M As(SG)3]. Incubations were performed at 37 degrees C in DME
      F12 buffer (95/5 O2/CO2) for 8 hr. Hg(SG)2 reduced slice K+/DNA content, as an
      indicator of viability, significantly less than HgCl2. As(SG)3 exhibited a 2-hr
      delay in K+/DNA content reduction compared to NaAsO2. This delay in toxicity was
      not correlated to changes in uptake. Arsenic and mercury accumulation, determined
      by proton-induced X-ray emission, were also identical between the metal salts and
      the metal-GSH conjugates. Exogenous GSH decreased HgCl2 cytotoxicity and was
      correlated to a decrease in Hg accumulation in the slice. Exogenous GSH had
      limited if any protective effects against cytotoxicity by NaAsO2 and a decrease
      in As accumulation was not observed. Complex metal-GSH interactions appear to
      exist and impact on the uptake and toxicity of these metals.

PMID- 7621808
TI  - Arsenic increased lipid peroxidation in rat tissues by a mechanism independent of
      glutathione levels.
AB  - The role of lipid peroxidation in the mechanism of arsenic toxicity was
      investigated in female rats pretreated with N-acetylcysteine (NAC, a glutathione
      [GSH] inducer) or with buthionine sulfoximine (BSO, a GSH depletor). Rats were
      challenged with sodium arsenite, and sacrificed 1 hr after this treatment.
      Results showed that arsenic decreased GSH levels and increased lipid peroxidation
      in liver, kidney, and heart, with a larger effect at 18.2 mg/kg than at 14.8
      mg/kg for lipid peroxidation induction. In the liver of rats treated with
      arsenic, pretreatment with NAC increased the levels of GSH and decreased lipid
      peroxidation. In kidney and heart, NAC pretreatment protected the tissues against
      arsenic-induced depletion of GSH levels, but the same degree of protection was
      not found for lipid peroxidation induction. In its turn, BSO had an additive
      effect with arsenic in lowering the levels of GSH in the liver and kidney, but an
      inverse correlation between GSH levels and lipid peroxidation was found only in
      liver. Arsenic content in tissues of rats pretreated with NAC was lower than in
      rats treated only with arsenic. In rats with depleted levels of GSH (BSO
      pretreated rats), a shift in arsenic tissue distribution was found, with higher
      levels in skin and lower levels in kidney. A clear tendency for a positive
      correlation between arsenic concentration and lipid peroxidation levels was found
      in liver, kidney, and heart.

PMID- 7621809
TI  - Relevance of risk assessment to exposed communities.
AB  - Current environmental policy tends to evaluate potential, theoretical exposure to
      health risks by evaluating one chemical or hazard at a time. Risk assessment
      techniques used by the U. S. Environmental Protection Agency (EPA) and other
      government agencies do not evaluate the cumulative impact of exposure to
      environmental contaminants. This problem is of particular significance to low
      income and minority populations who tend to live in neighborhoods and work in
      locations that involve exposure to pollutants in air, water, and workplace
      activity. Certain areas within the border typify this lifestyle. The problem is
      further complicated by the fact that EPA operates separate programs for different
      "media." Exposure patterns in the border suggest the need for a cross-media
      pollution prevention approach. Minority recruitment into health research, a
      coordination of research approaches and dollars, and new resources for effective
      monitoring of minority communities could provide a basic assessment of the risks
      and their sources. Further research into the cumulative impacts of prevalent
      subsets of chemicals is also needed. Recent efforts in the Great Lakes may
      provide a model for this type of regional, cross-border effort.

PMID- 7621811
TI  - Water quality problems in Nogales, Sonora.
AB  - This article presents the results of a transboundary water quality monitoring
      program at the two Nogales area in the Arizona-Sonora border region. The program
      was carried out jointly in 1990 by U.S. and Mexican institutions. The results
      show pollution problems due to deficiencies in Nogales, Sonora municipal sewerage
      system, causing not only sewage spills in several parts of the city but also
      creating occasional transboundary problems. The results also showed potential
      illegal dumping of industrial hazardous waste (VOCs) into Nogales' municipal
      sewerage system. All of the organic compounds found in the sewage samples are
      solvents frequently used by the border industry. Occasional brakes of pipes spill
      the pollutants into the Nogales Wash, a water stream that runs parallel to
      Nogales' main sewerage line. Samples of the municipal water system showed no
      traces of pollutants. However, two rounds of samples detected concentrations of
      VOCs in wells used to supply water by trucks to low income neighborhoods in
      Nogales, Sonora. Ironically, the pollution detected in these wells has a greater
      impact in low income groups of the city that pay three to four times more per
      liter of water they consume, than the rest of the inhabitants with clean water
      from the municipal system.

PMID- 7621810
TI  - Health effects of metals: a role for evolution?
AB  - Metals have been mined and used since ancient times. The industrial era has seen
      a sharp increase in both the amounts and variety of metals that find applications
      in industry. The inadvertent release of metals, such as from fossil fuel
      consumption, also adds to the global burden. A number of catastrophic outbreaks
      have alerted us to the occupational and environmental health risks. Life on this
      planet has evolved in the presence of metals. Cells learned to make use of the
      more abundant metals in the Archean oceans as an integral component in their
      structure and function. Today, we inherit these as the essential metals. At the
      same time, evolving life must have developed means of coping with the potentially
      toxic actions of metals. The appearance of oxygen in the atmosphere in the
      Precambrian period also resulted in cells both using and developing protective
      mechanisms against what must have been a highly toxic, reactive gas. Atmospheric
      oxygen must have increased the solubility of many metals as insoluble metal
      sulfides were oxidized to the more soluble sulfates. It may be no coincidence
      that the protective mechanisms for oxygen are also used to protect against a
      number of toxic metals. Selected examples are given on the role of evolution in
      metal toxicology, specifically, examples where the normal function of essential
      metals is deranged by competition with nonessential metals. Examples are also
      given of protective mechanisms that involve enzymes or cofactors involved in the
      oxygen defense system.

PMID- 7621812
TI  - Approaches for exposure characterization and data needs for hazardous waste site
      assessment.
AB  - This article provides an understanding of the approaches for determining exposure
      and dose to populations in the vicinity of hazardous waste sites. A review of the
      federal legislation and jurisdiction for assessments is provided, and the
      approaches of the U.S. Environmental Protection Agency and the Agency for Toxic
      Substances and Disease Registry are compared. These methods strive to aid in the
      evaluation of public health impacts of contaminants that were, are, or may be
      released to the community, and they are concerned with various aspects of the
      contaminant fate, human contact, and toxic response for chemicals of concern.
      Such approaches have been designed for generic contamination scenarios, but they
      aim to be applicable to a wide range of chemicals and sites in the real world.
      Along with any modeling framework for exposure and dose characterization,
      detailed information or real data are requisite for the completion of any site
      specific assessment. What kinds of data are needed and where they may be found
      are also discussed. A comprehensive framework for exposure characterization,
      recently proposed by Georgopoulos and Lioy, is outlined. The framework is one
      employing the following elements: chemodynamic analyses of sources and receptors;
      characterization of the target population; toxicokinetic/toxicodynamic analyses;
      uncertainty/error analyses; and evaluation of the characterization performance.

PMID- 7621813
TI  - Molecular evolution of plasminogen activator inhibitor-1 functional stability.
AB  - Plasminogen activator inhibitor-1 (PAI-1) is a member of the serine protease
      inhibitor (serpin) supergene family and a central regulatory protein in the blood
      coagulation system. PAI-1 is unique among serpins in exhibiting distinct active
      and inactive (latent) conformations in vivo. Though the structure of latent PAI-1
      was recently solved, the structure of the short-lived, active form of PAI-1 is
      not known. In order to probe the structural basis for this unique conformational
      change, a randomly mutated recombinant PAI-1 expression library was constructed
      in bacteriophage and screened for increased functional stability. Fourteen unique
      clones were selected, and shown to exhibit functional half-lives (T1/2S)
      exceeding that of wild-type PAI-1 by up to 72-fold. The most stable variant (T1/2
      = 145 h) contained four mutations. Detailed analysis of these four mutations,
      individually and in combination, demonstrated that the markedly enhanced
      functional stability of the parent compound mutant required contributions from
      all four substitutions, with no individual T1/2 exceeding 6.6 h. The functional
      stability of at least eight of the remaining 13 compound mutants also required
      interactions between two or more amino acid substitutions, with no single variant
      increasing the T1/2 by > 10-fold. The nature of the identified mutations implies
      that the unique instability of the PAI-1 active conformation evolved through
      global changes in protein packing and suggest a selective advantage for transient
      inhibitor function.

PMID- 7621814
TI  - The unique extracellular disulfide loop of the glycine receptor is a principal
      ligand binding element.
AB  - A loop structure, formed by the putative disulfide bridging of Cys198 and Cys209,
      is a principal element of the ligand binding site in the glycine receptor (GlyR).
      Disruption of the loop's tertiary structure by Ser mutations of these Cys
      residues either prevented receptor assembly on the cell surface, or created
      receptors unable to be activated by agonists or to bind the competitive
      antagonist, strychnine. Mutation of residues Lys200, Tyr202 and Thr204 within
      this loop reduced agonist binding and channel activation sensitivities by up to
      55-, 520- and 190-fold, respectively, without altering maximal current sizes, and
      mutations of Lys200 and Tyr202 abolished strychnine binding to the receptor.
      Removal of the hydroxyl moiety from Tyr202 by mutation to Phe profoundly reduced
      agonist sensitivity, whilst removal of the benzene ring abolished strychnine
      binding, thus demonstrating that Tyr202 is crucial for both agonist and
      antagonist binding to the GlyR. Tyr202 also influences receptor assembly on the
      cell surface, with only large chain substitutions (Phe, Leu and Arg, but not Thr,
      Ser and Ala) forming functional receptors. Our data demonstrate the presence of a
      second ligand binding site in the GlyR, consistent with the three-loop model of
      ligand binding to the ligand-gated ion channel superfamily.

PMID- 7621815
TI  - Ca(2+)-induced Ca2+ release in myocytes from dyspedic mice lacking the type-1
      ryanodine receptor.
AB  - While subtypes 1 and 2 of the ryanodine receptor (RyR) function as intracellular
      Ca2+ release channels, little is known about the function of the third subtype
      (RyR-3), first identified in brain. Myocytes from mice homozygous for a targeted
      mutation in the RyR-1 gene (dyspedic mice) can now be used for a study on the
      function of RyR-3, which is predominantly expressed in these cells according to
      our reverse transcription-polymerase chain reaction analysis. We here demonstrate
      in these myocytes caffeine-, ryanodine- and adenine nucleotide-sensitive Ca(2+)
      induced Ca2+ release with approximately 10 times lower sensitivity to Ca2+ than
      that of RyR-1. Although RyR-3 does not mediate excitation-contraction coupling of
      the skeletal muscle type, we propose that RyR-3 may induce intracellular Ca2+
      release in response to a Ca2+ rise with a high threshold.

PMID- 7621816
TI  - malvolio, the Drosophila homologue of mouse NRAMP-1 (Bcg), is expressed in
      macrophages and in the nervous system and is required for normal taste behaviour.
AB  - We report the sequence, expression pattern and mutant phenotype of malvolio
      (mvl), the Drosophila homologue of mammalian natural resistance-associated
      macrophage proteins (NRAMPs). In the mouse, this novel transporter is encoded by
      Bcg, a dominant gene that confers natural resistance to intracellular parasites.
      mvl was identified in a screen for mutants that affect taste behaviour. We show
      that loss-of-function as well as insertional mutants in mvl display defects in
      taste behaviour with no alterations in the physiology of the sensory neurons.
      Activity of the reporter enzyme beta-galactosidase, that reflects the expression
      pattern of mvl, is seen in mature sensory neurons and in macrophages. The
      conceptual translation of the mvl cDNA shows a striking similarity (65% identity)
      with human NRAMP with almost complete identity in a conserved consensus motif
      found in a number of ATP-coupled transporters. Based on its phenotype and
      expression pattern as well as its structural similarities to NRAMPs and a nitrate
      transporter in Aspergillus nidulans, we discuss a possible role for MVL in
      nitrite/nitrate transport and its implications.

PMID- 7621817
TI  - A potassium transporter of the yeast Schwanniomyces occidentalis homologous to
      the Kup system of Escherichia coli has a high concentrative capacity.
AB  - The yeast Schwanniomyces occidentalis has a high-affinity K+ uptake system with a
      high concentrative capacity, which is able to deplete the external K+ to < 0.03
      microM. We have cloned the gene HAK1 of S.occidentalis which complements
      defective K+ uptake by trk1 and trk1 trk2 mutants of Saccharomyces cerevisiae.
      When HAK1 was expressed in a trk1 trk2 S.cerevisiae mutant, transport affinities
      for K+ and other alkali cations resembled those of S.occidentalis. The predicted
      amino acid sequence of the HAK1 protein shows significant homology with the
      hydrophobic region of the Kup transporter of Escherichia coli. In S.occidentalis
      HAK1 expresses in K(+)-limiting conditions. Our data indicate that in K(+)
      starved cells the system encoded by HAK1 is the major K+ transporter of
      S.occidentalis.

PMID- 7621819
TI  - CNTF variants with increased biological potency and receptor selectivity define a
      functional site of receptor interaction.
AB  - Human CNTF is a neurocytokine that elicits potent neurotrophic effects by
      activating a receptor complex composed of the ligand-specific alpha-receptor
      subunit (CNTFR alpha) and two signal transducing proteins, which together
      constitute a receptor for leukemia inhibitory factor (LIFR). At high
      concentrations, CNTF can also activate the LIFR and possibly other cross-reactive
      cytokine receptors in the absence of CNTFR alpha. To gain a better understanding
      of its structure-function relationships and to develop analogs with increased
      receptor specificity, the cytokine was submitted to affinity maturation using
      phage display technology. Variants with greatly increased CNTFR alpha affinity
      were selected from a phage-displayed library of CNTF variants carrying random
      amino acid substitutions in the putative D helix. Selected variants contained
      substitutions of the wild-type Gln167 residue, either alone or in combination
      with neighboring mutations. These results provide evidence for an important
      functional role of the mutagenized region in CNTFR alpha binding. Affinity
      enhancing mutations conferred to CNTF increased potency to trigger biological
      effects mediated by CNTFR alpha and enhanced neurotrophic activity on chicken
      ciliary neurons. In contrast, the same mutations did not potentiate the CNTFR
      alpha-independent receptor actions of CNTF. These CNTF analogs thus represent
      receptor-specific superagonists, which should help to elucidate the mechanisms
      underlying the pleiotropic actions of the neurocytokine.

PMID- 7621818
TI  - Phosphorylation of presynaptic and postsynaptic calcium channels by cAMP
      dependent protein kinase in hippocampal neurons.
AB  - Phosphorylation by cAMP-dependent protein kinase (PKA) and other second messenger
      activated protein kinases modulates the activity of a variety of effector
      proteins including ion channels. Anti-peptide antibodies specific for the alpha 1
      subunits of the class B, C or E calcium channels from rat brain specifically
      recognize a pair of polypeptides of 220 and 240 kDa, 200 and 220 kDa, and 240 and
      250 kDa, respectively, in hippocampal slices in vitro. These calcium channels are
      localized predominantly on presynaptic and dendritic, somatic and dendritic, and
      somatic sites, respectively, in hippocampal neurons. Both size forms of alpha 1B
      and alpha 1E and the full-length form of alpha 1C are phosphorylated by PKA after
      solubilization and immunoprecipitation. Stimulation of PKA in intact hippocampal
      slices also induced phosphorylation of 25-50% of the PKA sites on class B N-type
      calcium channels, class C L-type calcium channels and class E calcium channels,
      as assessed by a back-phosphorylation method. Tetraethylammonium ion (TEA), which
      causes neuronal depolarization and promotes repetitive action potentials and
      neurotransmitter release by blocking potassium channels, also stimulated
      phosphorylation of class B, C and E alpha 1 subunits, suggesting that these three
      classes of channels are phosphorylated by PKA in response to endogenous
      electrical activity in the hippocampus. Regulation of calcium influx through
      these calcium channels by PKA may influence calcium-dependent processes within
      hippocampal neurons, including neurotransmitter release, calcium-activated
      enzymes and gene expression.

PMID- 7621820
TI  - E5 oncoprotein retained in the endoplasmic reticulum/cis Golgi still induces PDGF
      receptor autophosphorylation but does not transform cells.
AB  - The E5 oncoprotein encoded by bovine papillomavirus type 1 is a homodimeric,
      hydrophobic polypeptide which is localized predominantly in Golgi membranes and
      which transforms several cell types apparently by inducing tyrosine
      phosphorylation of the platelet-derived growth factor receptor (PDGF-R). While
      the precise mechanism of receptor activation is unknown, E5 associates with
      several cellular proteins, including PDGF-R and the 16K V-ATPase protein, and
      induces the preferential phosphorylation of immature, Endo H-sensitive forms of
      the receptor. To evaluate whether E5 accumulation in the Golgi was requisite for
      receptor phosphorylation and cell transformation, we sequestered the E5 protein
      in the endoplasmic reticulum (ER)/cis Golgi by appending the ER retention KDEL
      sequence to its C-terminus. In transient assays and in cell lines, E5/KDEL
      protein and E5/KDEL* protein (a defective variant of KDEL), were stable and
      formed homodimers normally. E5/KDEL*, similar to wt E5, localized to the Golgi
      and was transformation-proficient. In contrast, E5/KDEL failed to concentrate in
      the Golgi and was transformation-incompetent. Despite these critical defects,
      however, E5/KDEL formed stable complexes with immature PDGF-R and 16K and, even
      more unexpectedly, induced the phosphorylation of both mature and immature PDGF-R
      on tyrosine residues to the same level as wt E5. These data demonstrate that E5
      can bind and induce PDGF-R phosphorylation in the ER/cis Golgi, but that
      successful mitogenic signalling (and consequent cell transformation) requires the
      translocation of E5/receptor complexes to distal Golgi compartments.

PMID- 7621821
TI  - The calnexin homologue cnx1+ in Schizosaccharomyces pombe, is an essential gene
      which can be complemented by its soluble ER domain.
AB  - Secretory proteins become folded by the action of a number of molecular
      chaperones soon after they enter the endoplasmic reticulum (ER). In mammalian
      cells, the ER membrane protein calnexin has been shown to be a molecular
      chaperone involved in the folding of secretory proteins and in the assembly of
      cell surface receptor complexes. We have used a PCR strategy to identify the
      Schizosaccharomyces pombe calnexin homologue, cnx1+. The cnx1+ encoded protein,
      Cnx1, was shown to be a calcium binding type I integral membrane glycoprotein. At
      its 5' end, the cnx1+ gene has consensus heat shock transcriptional control
      elements and was inducible by heat shock and by the calcium ionophore A23187.
      Unlike the sequence-related Saccharomyces cerevisiae CNE1 gene, the S.pombe cnx1+
      gene was essential for cell viability. The full-length Cnx1 protein was able to
      complement the cnx1+ gene disruption but the full-length mammalian calnexin could
      not. The ER lumenal domain of Cnx1, which was secreted from cells, was capable of
      complementing the cnx1::ura4 lethal phenotype. The equivalent region of mammalian
      calnexin has been shown to possess molecular chaperone activity. It is possible
      that the lethal phenotype is caused by the absence of this chaperone activity in
      the S.pombe cnx1+ gene disruption.

PMID- 7621822
TI  - Tyrosine O-sulfation promotes proteolytic processing of progastrin.
AB  - Tyrosine O-sulfation is a common post-translational modification of secretory and
      membrane proteins. The biological function of sulfation is known in only a few
      proteins, where it appears to enhance protein-protein interactions. Based on
      known sequences around sulfated tyrosines, a consensus sequence for prediction of
      target tyrosines has been proposed. However, some proteins are tyrosine sulfated
      at sites that deviate from the proposed consensus. Among these is progastrin. It
      is possible that the deviation explains the incomplete sulfation characteristic
      for bioactive gastrin peptides. In order to test this hypothesis, we have
      performed site-directed mutagenesis of the gastrin gene followed by heterologous
      expression in an endocrine cell line. The results show that substitution of the
      alanyl residue immediately N-terminal to the sulfated tyrosine with an acidic
      amino acid promotes the sulfation of gastrin peptides. Hence, the study supports
      the proposed consensus sequence for tyrosine sulfation. Importantly, however, the
      results also reveal that complete sulfation increases the endoproteolytic
      maturation of progastrin. Thus, our study suggests an additional function for
      tyrosine sulfation of possible general significance.

PMID- 7621823
TI  - The role of inositol acylation and inositol deacylation in GPI biosynthesis in
      Trypanosoma brucei.
AB  - The compound diisopropylfluorophosphate (DFP) selectively inhibits an inositol
      deacylase activity in living trypanosomes that, together with the previously
      described phenylmethylsulfonyl fluoride (PMSF)-sensitive inositol
      acyltransferase, maintains a dynamic equilibrium between the
      glycosylphosphatidylinositol (GPI) anchor precursor, glycolipid A [NH2(CH2)2PO4
      6Man alpha 1-2Man alpha 1-6Man alpha 1-4GlcN alpha 1-6myo-inositol-1-PO4-sn-1,2
      dimyristoylglycerol], and its inositol acylated form, glycolipid C. Experiments
      using DFP in living trypanosomes and a trypanosome cell-free system suggest that
      earlier GPI intermediates are also in equilibrium between their inositol acylated
      and nonacylated forms. However, unlike mammalian and yeast cells, bloodstream
      form trypanosomes do not appear to produce an inositol acylated form of
      glucosaminylphosphatidylinositol (GlcN-PI). A specific function of inositol
      acylation in trypanosomes may be to enhance the efficiency of ethanolamine
      phosphate addition to the Man3GlcN-(acyl)PI intermediate. Inositol deacylation
      appears to be a prerequisite for fatty acid remodelling of GPI intermediates that
      leads to the exclusive presence of myristic acid in glycolipid A and, ultimately,
      in the variant surface glycoprotein (VSG). In the presence of DFP, the de novo
      synthesis of GPI precursors cannot proceed beyond glycolipid C' (the unremodelled
      version of glycolipid C) and lyso-glycolipid C'. Under these conditions
      glycolipid C'-type GPI anchors appear on newly synthesized VSG molecules.
      However, the efficiencies of both anchor addition to VSG and N-glycosylation of
      VSG were significantly reduced. A modified model of the GPI biosynthetic pathway
      in bloodstream form African trypanosomes incorporating these findings is
      presented.

PMID- 7621824
TI  - hsk1+, a Schizosaccharomyces pombe gene related to Saccharomyces cerevisiae CDC7,
      is required for chromosomal replication.
AB  - Degenerate oligonucleotide-directed polymerase chain reaction was conducted to
      clone a possible Schizosaccharomyces pombe homologue [hsk1 for a putative
      homologue of CDC7 (seven) kinase 1] of Saccharomyces cerevisiae Cdc7 kinase. The
      cloned cDNA for hsk1+ contains an open reading frame consisting of 507 amino
      acids with predicted mol. wt of 58,370 that possesses overall amino acid identity
      of 46% (65% including similar residues) to CDC7. In addition to conserved domains
      for serine-threonine kinases, the predicted primary structure of Hsk1 contains
      three 'kinase insert' sequences characteristic to Cdc7 at the positions identical
      to those of Cdc7. Whereas the length and sequences of the kinase inserts are
      diverged between the two yeast species, 58% identity (76% including similar
      residues) is detected within the kinase conserved domains. The hsk1+ gene, which
      is present as a single copy on the S.pombe chromosome, contains two introns
      within the coding frame. Disruption of the hsk1+ gene by insertion of the ura4+
      gene is lethal to growth. Analysis of the DNA content of germinating spores that
      contain hsk1 null alleles indicates that DNA replication is inhibited in the
      mutant. The morphology of these mutant spores after germination indicates
      abnormal nuclear division in some population of germinating spores, suggesting
      either that Hsk1 may be required for inhibition of mitosis until completion of S
      phase or that it may also be involved in proper execution of mitosis. Our results
      suggest that hsk1+ is a strong candidate for the functional fission yeast
      homologue of budding yeast CDC7 and that a mechanism through which initiation of
      chromosomal replication is regulated may be conserved between the two yeast
      species.

PMID- 7621825
TI  - Nin1p, a regulatory subunit of the 26S proteasome, is necessary for activation of
      Cdc28p kinase of Saccharomyces cerevisiae.
AB  - The nin1-1 mutant of Saccharomyces cerevisiae cannot perform the G1/S and G2/M
      transitions at restrictive temperatures. At such temperatures, nin1-1 strains
      fail to activate histone H1 kinase after release from alpha factor-imposed G1
      block and after release from hydroxyurea-imposed S block. The nin1-1 mutation
      shows synthetic lethality with certain cdc28 mutant alleles such as cdc28-IN. Two
      lines of evidence indicate that Nin1p is a component of the 26S proteasome
      complex: (i) Nin1p, as well as the known component of the 26S proteasome, shifted
      to the 26S proteasome peak in the glycerol density gradient after preincubation
      of crude extract with ATP-Mg2+, and (ii) nin1-1 cells accumulated
      polyubiquitinated proteins under restrictive conditions. These results suggest
      that activation of Cdc28p kinase requires proteolysis. We have cloned a human
      cDNA encoding a regulatory subunit of the 26S proteasome, p31, which was found to
      be a homolog of Nin1p.

PMID- 7621826
TI  - Membrane-bound LERK2 ligand can signal through three different Eph-related
      receptor tyrosine kinases.
AB  - The Eph-related family of receptor tyrosine kinases consists of at least 13
      members, several of which display distinctive expression patterns in the
      developing and adult nervous system. Recently, a small family of ligands,
      structurally related to the B61 protein, was identified. Binding of these ligands
      to Eph-related receptors did not, however, elicit measurable biological signals
      in cultured cells. In order to study functional interactions between B61-related
      ligands and Eph-related receptors, we constructed chimeric receptors, containing
      an Eph-related ectodomain and the cytoplasmic domain of the TrkB neurotrophin
      receptor. Expression and activation of such chimeric receptors in NIH 3T3 cells
      induced transformation in focus formation assays. Membrane-bound LERK2 ligand is
      shown to signal through three different Eph-related receptors, namely Cek5, Cek10
      and Elk. LERK2, however, fails to interact functionally with the Cek9 receptor.
      Quantitative analysis including binding assays indicates that Cek10 is the
      preferred LERK2 receptor. Preliminary mutagenesis of the LERK2 protein suggests a
      negative regulatory role for its cytoplasmic domain in LERK2 signaling.

PMID- 7621827
TI  - 3BP-1, an SH3 domain binding protein, has GAP activity for Rac and inhibits
      growth factor-induced membrane ruffling in fibroblasts.
AB  - The SH3 binding protein, 3BP-1, was originally cloned as a partial cDNA from an
      expression library using the Abl SH3 domain as a probe. In addition to an SH3
      binding domain, 3BP-1 displayed homology to a class of GTPase activating proteins
      (GAPs) active against Rac and Rho proteins. We report here a full length cDNA of
      3BP-1 which extends the homology to GAP proteins previously noted. 3BP-1
      functions in vitro as a GAP with a specificity for Rac-related G proteins.
      Microinjection of the 3BP-1 protein into serum-starved fibroblasts produces an
      inhibition of platelet-derived growth factor (PDGF)-induced membrane ruffling
      mediated by Rac. Co-injection of 3BP-1 with an activated Rac mutant that is
      unresponsive to GAPs, counter-acts this inhibition. 3BP-1 does not show in vitro
      activity towards Rho and, in agreement with this finding, microinjection of 3BP-1
      into fibroblasts has no effect on lysophosphatidic acid (LPA)-induced stress
      fiber assembly mediated by Rho. Thus 3BP-1 is a new and specific Rac GAP that can
      act in cells to counter Rac-mediated membrane ruffling. How its SH3 binding site
      interacts with its GAP activity remains to be understood.

PMID- 7621828
TI  - The dorsal-related immunity factor, Dif, is a sequence-specific trans-activator
      of Drosophila Cecropin gene expression.
AB  - A new member of the Rel family of transcription factors, the dorsal-related
      immunity factor, Dif, was recently cloned and suggested to be involved in
      regulating the immune response in Drosophila. Despite its classification as a Rel
      family member, the Dif cDNA-encoded product has not been proven previously to be
      a transcription factor. We now present evidence that the Dif gene product trans
      activates the Drosophila Cecropin A1 gene in co-transfection assays. The
      transactivation requires a 40 bp upstream element including an insect kappa B
      like motif. A dimer of the kappa B-like motif 5'-GGGGATTTTT inserted into a
      minimal promoter conferred high levels of reporter gene expression by Dif, while
      a multimer of several mutated versions of this motif was not activated,
      demonstrating the sequence specificity of Dif. Full trans-activation by Dif
      requires the C-terminal part of the protein. The morphogen dorsal (dl) can also
      activate the Cecropin A1 promoter, but to a lesser extent and in a less sequence
      specific manner than Dif. Simultaneous overexpression of Dif and dl in co
      transfection assays revealed that dl possesses a dominant negative effect on Dif
      transactivation. This study establishes that Dif is a sequence-specific
      transcription factor and is probably a key activator of the immune response in
      Drosophila.

PMID- 7621829
TI  - BS69, a novel adenovirus E1A-associated protein that inhibits E1A
      transactivation.
AB  - The adenovirus E1A gene products are nuclear phosphoproteins that can
      transactivate the other adenovirus early genes as well as several cellular genes,
      and can transform primary rodent cells in culture. Transformation and
      transactivation by E1A proteins is most likely to be mediated through binding to
      several cellular proteins, including the retinoblastoma gene product pRb, the pRb
      related p107 and p130, and the TATA box binding protein TBP. We report here the
      cloning of BS69, a novel protein that specifically interacts with adenovirus 5
      E1A. BS69 has no significant homology to known proteins and requires the region
      that is unique to the large (289R) E1A protein for high affinity binding. BS69
      and E1A proteins coimmunoprecipitate in adenovirus-transformed 293 cells,
      indicating that these proteins also interact in vivo. BS69 specifically inhibits
      transactivation by the 289R E1A protein, but not by the 243R E1A protein. BS69
      also suppressed the E1A-stimulated transcription of the retinoic acid receptor in
      COS cells, but did not affect the cellular E1A-like activity that is present in
      embryonic carcinoma cells. Our data indicate that BS69 is a novel and specific
      suppressor of E1A-activated transcription.

PMID- 7621830
TI  - CRP2 (C/EBP beta) contains a bipartite regulatory domain that controls
      transcriptional activation, DNA binding and cell specificity.
AB  - Two members of the C/EBP family of basic region-leucine zipper proteins enriched
      in the liver, C/EBP (C/EBP alpha) and CRP2 (C/EBP beta), were previously shown to
      transactivate the albumin promoter in a cell type-dependent manner. These
      proteins function efficiently in HepG2 hepatoma cells, but inefficiently in HeLa
      (epithelial) and L (fibroblastic) cells. Here we have investigated the mechanism
      for cell-specific control of CRP2 activity. We show that CRP2 contains a negative
      regulatory region composed of two elements, RD1 and RD2. Deletions of RD2 relieve
      the inhibition of CRP2 activity in L cells, but do not affect CRP2 function in
      HepG2 cells. These deletions also increase the DNA binding activity of CRP2
      approximately 3-fold, suggesting that RD2-mediated repression of DNA binding
      activity is responsible for CRP2 inhibition in L cells. The adjacent RD1 element
      functions independently of RD2 and modulates the CRP2 activation domain, which we
      show to be composed of three subdomains that are conserved within the C/EBP
      protein family. RD1 does not affect cell type specificity, but inhibits the
      transactivation potential of GAL4-CRP2 hybrid proteins by 50-fold. These findings
      suggest that CRP2 assumes a tightly folded conformation in which the DNA binding
      and activation domains are masked by interactions with the regulatory domain and
      that to function efficiently in HepG2 cells the protein must undergo an
      activation step. We propose that relief of inhibition conferred by the regulatory
      domains also accounts for CRP2 activation in response to extracellular signals.

PMID- 7621831
TI  - GCN20, a novel ATP binding cassette protein, and GCN1 reside in a complex that
      mediates activation of the eIF-2 alpha kinase GCN2 in amino acid-starved cells.
AB  - GCN2 is a protein kinase that phosphorylates the alpha-subunit of translation
      initiation factor 2 (eIF-2) and thereby stimulates translation of GCN4 mRNA in
      amino acid-starved cells. We isolated a null mutation in a previously
      unidentified gene, GCN20, that suppresses the growth-inhibitory effect of eIF-2
      alpha hyperphosphorylation catalyzed by mutationally activated forms of GCN2. The
      deletion of GCN20 in otherwise wild-type strains impairs derepression of GCN4
      translation and reduces the level of eIF-2 alpha phosphorylation in vivo, showing
      that GCN20 is a positive effector of GCN2 kinase function. In accordance with
      this conclusion, GCN20 was co-immunoprecipitated from cell extracts with GCN1,
      another factor required to activate GCN2, and the two proteins interacted in the
      yeast two-hybrid system. We conclude that GCN1 and GCN20 are components of a
      protein complex that couples the kinase activity of GCN2 to the availability of
      amino acids. GCN20 is a member of the ATP binding cassette (ABC) family of
      proteins and is closely related to ABC proteins identified in Caenorhabditis
      elegans, rice and humans, suggesting that the function of GCN20 may be conserved
      among diverse eukaryotic organisms.

PMID- 7621832
TI  - Rationally designed helix-turn-helix proteins and their conformational changes
      upon DNA binding.
AB  - Circular dichroism and electrophoretic mobility shift studies were performed to
      confirm that dimerized N-terminal domains of bacterial repressors containing
      helix-turn-helix motifs are capable of high-affinity and specific DNA recognition
      as opposed to the monomeric N-terminal domains. Specific, high-affinity DNA
      binding proteins were designed and produced in which two copies of the N-terminal
      1-62 domain of the bacteriophage 434 repressor are connected either in a dyad
      symmetric fashion, with a synthetic linker attached to the C-termini, or as
      direct sequence repeats. Both molecules bound to their presumptive cognate nearly
      as tightly as does the natural (full-length and non-covalently dimerized) 434
      repressor, showing that covalent dimerization can be used to greatly enhance the
      binding activity of individual protein segments. Circular dichroism spectroscopy
      showed a pronounced increase in the alpha-helix content when these new proteins
      interacted with their cognate DNA and a similar, although 30% lower, increase was
      also seen upon their interaction with non-cognate DNA. These results imply that a
      gradual conformational change may occur when helix-turn-helix motifs bind to DNA,
      and that a scanning mechanism is just as plausible for this motif class as that
      which is proposed for the more flexible basic-leucine zipper and basic-helix-loop
      helix motifs.

PMID- 7621833
TI  - Trans-kingdom T-DNA transfer from Agrobacterium tumefaciens to Saccharomyces
      cerevisiae.
AB  - Agrobacterium tumefaciens transfers part of its tumour-inducing (Ti) plasmid, the
      transferred or T-DNA, to plants during tumourigenesis. This represents the only
      example of naturally occurring trans-kingdom transfer of genetic material. Here
      we report that A.tumefaciens can transfer its T-DNA not only to plant cells, but
      also to another eukaryote, namely the yeast Saccharomyces cerevisiae. The Ti
      plasmid virulence (vir) genes that mediate T-DNA transfer to plants were found to
      be essential for transfer to yeast as well. Transgenic S.cerevisiae strains were
      analysed for their T-DNA content. Results showed that T-DNA circles were formed
      in yeast with precise fusions between the left and right borders. Such T-DNA
      circles were stably maintained by the yeast if the replicator from the yeast 2 mu
      plasmid was present in the T-DNA. Integration of T-DNA in the S.cerevisiae genome
      was found to occur via homologous recombination. This contrasts with integration
      in the plant genome, where T-DNA integrates preferentially via illegitimate
      recombination. Our results thus suggest that the process of T-DNA integration is
      predominantly determined by host factors.

PMID- 7621834
TI  - Unwinding of chromatin by the SV40 large T antigen DNA helicase.
AB  - We have analysed the unwinding of nucleosomally organized DNA by simian virus 40
      large tumour (T) antigen. Isolated T antigen can bind to existing nucleosome
      cores containing the viral replication origin sequence, which results in
      displacement of the histone octamer and unwinding of the DNA. However, specific
      binding to nucleosome cores is salt sensitive and nearly completely blocked under
      ionic conditions that otherwise support DNA replication. Once started, the
      progressing T antigen helicase, like an elongating RNA polymerase, is not further
      repressed by histone octamers, irrespective of the presence or absence of linker
      histone H1. Disruption of the nucleosomal structure in the process of unwinding
      may be assisted by the demonstrated interaction of the hexameric T antigen
      complex with histone proteins H1 and H3. Finally, our studies reveal the
      inability of topoisomerase I and/or II to continually relieve the superhelical
      tension of covalently closed circular minichromosomes as generated during their
      unwinding by T antigen. This may indicate that chromatin relaxation during the
      process of DNA replication can only be efficiently performed by a topoisomerase
      that is (trans)activated by other factors.

PMID- 7621835
TI  - Interactions between the terminal bases of mammalian introns are retained in
      inosine-containing pre-mRNAs.
AB  - Nuclear pre-mRNA splicing has a fundamentally similar two-step mechanism to that
      employed by group II self-splicing introns. It is believed that nuclear pre-mRNA
      splicing involves a network of RNA-RNA interactions which form the catalytic core
      of the active spliceosome. We show here a non-Watson-Crick interaction between
      the first and last guanosine residues of a mammalian intron. As in Saccharomyces
      cerevisiae, substitution of the conserved guanosines at the 5' and 3' splice
      sites by A and C respectively, specifically suppresses step 2 splicing defects
      resulting from the individual mutations. No other combination of terminal
      nucleotides was able to restore splicing. We additionally provide independent
      evidence for an indirect interaction between other nucleotides of the consensus
      splice sites during step 2 of splicing. Substitution of the nucleotide in the +3
      position of the 5' splice site affects competition between closely spaced AG
      dinucleotides at the 3' splice site, although the interaction is not via direct
      differential base pairing. Finally, we show that complete substitution of
      guanosine residues by inosine in a pre-mRNA has only a modest effect upon step 2
      of splicing, although earlier spliceosome assembly steps are impaired.
      Predictions can thus be made about the precise configuration of the non-Watson
      Crick interaction between the terminal residues.

PMID- 7621836
TI  - Enhancement of Neurospora VS ribozyme cleavage by tuberactinomycin antibiotics.
AB  - Several examples of inhibition of the function of a ribozyme or RNA-protein
      complex have shown that certain antibiotics can interact specifically with RNA.
      There are, however, few examples of antibiotics that have a positive, rather than
      a negative, effect on the function of an RNA. We have found that micromolar
      concentrations of viomycin, a basic, cyclic peptide antibiotic of the
      tuberactinomycin group, enhance the cleavage of a ribozyme derived from
      Neurospora VS RNA. Viomycin decreases by an order of magnitude the concentration
      of magnesium required for cleavage. It also stimulates an otherwise insignificant
      transcleavage reaction by enhancing interactions between RNA molecules. The
      ability of viomycin to enhance some RNA-mediated reactions but inhibit others,
      including translation and Group I intron splicing, demonstrates the potential for
      natural selection by small molecules during evolution in the 'RNA world' and may
      have broader implications with respect to ribozyme expression and activity in
      contemporary cells.

PMID- 7621837
TI  - Genetic code deviations in the ciliates: evidence for multiple and independent
      events.
AB  - In several species of ciliates, the universal stop codons UAA and UAG are
      translated into glutamine, while in the euplotids, the glutamine codon usage is
      normal, but UGA appears to be translated as cysteine. Because the emerging
      position of this monophyletic group in the eukaryotic lineage is relatively late,
      this deviant genetic code represents a derived state of the universal code. The
      question is therefore raised as to how these changes arose within the
      evolutionary pathways of the phylum. Here, we have investigated the presence of
      stop codons in alpha tubulin and/or phosphoglycerate kinase gene coding sequences
      from diverse species of ciliates scattered over the phylogenetic tree constructed
      from 28S rRNA sequences. In our data set, when deviations occur they correspond
      to in frame UAA and UAG coding for glutamine. By combining these new data with
      those previously reported, we show that (i) utilization of UAA and UAG codons
      occurs to different extents between, but also within, the different classes of
      ciliates and (ii) the resulting phylogenetic pattern of deviations from the
      universal code cannot be accounted for by a scenario involving a single
      transition to the unusual code. Thus, contrary to expectations, deviations from
      the universal genetic code have arisen independently several times within the
      phylum.

PMID- 7621838
TI  - An enzyme in yeast mitochondria that catalyzes a step in branched-chain amino
      acid biosynthesis also functions in mitochondrial DNA stability.
AB  - The yeast mitochondrial high mobility group protein Abf2p is required, under
      certain growth conditions, for the maintenance of wild-type (rho+) mitochondrial
      DNA (mtDNA). We have identified a multicopy suppressor of the mtDNA instability
      phenotype of cells with a null allele of the ABF2 gene (delta abf2). The
      suppressor is a known gene, ILV5, encoding the mitochondrial protein,
      acetohydroxy acid reductoisomerase, which catalyzes a step in branched-chain
      amino acid biosynthesis. Efficient suppression occurs with just a 2- to 3-fold
      increase in ILV5 copy number. Moreover, in delta abf2 cells with a single copy of
      ILV5, changes in mtDNA stability correlate directly with changes in conditions
      that are known to affect ILV5 expression. Wild-type mtDNA is unstable in cells
      with an ILV5 null mutation (delta ilv5), leading to the production of mostly rho-
      petite mutants. The instability of rho+ mtDNA in delta ilv5 cells is not simply a
      consequence of a block in branched-chain amino acid biosynthesis, since mtDNA is
      stable in cells with a null allele of the ILV2 gene, which encodes another enzyme
      of that pathway. The most severe instability of rho+ mtDNA is observed in cells
      with null alleles of both ABF2 and ILV5. We suggest that ILV5 encodes a
      bifunctional protein required for branched-chain amino acid biosynthesis and for
      the maintenance of rho+ mtDNA.

PMID- 7621839
TI  - Specific mutations in alpha- and gamma-subunits of F1-ATPase affect mitochondrial
      genome integrity in the petite-negative yeast Kluyveromyces lactis.
AB  - We have shown previously that mutations in nuclear genes, termed MGI, for
      mitochondrial genome integrity, can convert the petite-negative yeast
      Kluyveromyces lactis into a petite-positive form with the ability to produce
      mitochondrial genome deletion mutants (Chen and Clark-Walker, Genetics, 133, 517
      525, 1993). Here we describe that two genes, MGI2 and MGI5, encode the alpha- and
      gamma-subunits of mitochondrial F1-ATPase. Specific mutations, Phe443-->Ser and
      Ala333-->Val in MGI2, and Thr275-->Ala in MGI5, confer on cells the ability to
      produce petite mutants spontaneously with deletions in mitochondrial (mt) DNA and
      the capacity to lose their mitochondrial genomes upon treatment with ethidium
      bromide. Structural integrity of the F1 complex seems to be needed for expression
      of the Mgi- phenotype as null mutations in MGI2 and MGI5 remove the ability to
      form mtDNA deletions. It is suggested that mgi mutations allow petites to survive
      because an aberrant F1 complex prevents collapse of the mitochondrial inner
      membrane potential that normally occurs on loss of mtDNA-encoded F0 subunits.

PMID- 7621840
TI  - Vasodilation-related adverse events in diltiazem and dihydropyridine calcium
      antagonists studied by prescription-event monitoring.
AB  - The incidence of vasodilation-related events (flushing, headache, dizziness and
      oedema) was determined in a total of 37,670 patients treated with diltiazem,
      nicardipine, isradipine or amlodipine and studied by Prescription-Event
      Monitoring between 1984 and 1991. Event rates are expressed as the percentage of
      patients who experienced these events during the six months after the first
      prescription. The rates for all these events with the newer vasoselective
      dihydropyridines (nicardipine, isradipine and amlodipine) were higher than those
      with diltiazem. Among the three dihydropyridines, there were large individual
      differences in the rates. With nicardipine, the frequency of each of the four
      vasodilation-related events were similar to one another (approximately 3%). With
      isradipine, the rates were also similar to one another but all were approximately
      twice those measured in the nicardipine study (approximately 6%). These
      differences may have been due to confounding factors such as the publicity about
      adverse drug reactions, the indication for use by individual patients or the
      doses actually being used at the time the event occurred. With amlodipine, in
      contrast, the rate for oedema was two to four times larger than the rates for
      flushing, headache or dizziness.

PMID- 7621841
TI  - A comparison of the effects of prednisolone and mianserin on ventilatory,
      exercise and psychometric parameters in patients with chronic obstructive
      pulmonary disease.
AB  - There is controversy as to whether effects on mood play a role in mediating the
      response to corticosteroids in chronic obstructive pulmonary disease (COPD). If
      alterations in mood are important, it is conceivable that psychotropic drugs such
      as mianserin might produce similar responses to prednisolone in patients with
      COPD. Twelve patients age 62.5 y, with FEV1 29% of predicted and < 15%
      reversibility to salbutamol completed a randomised, double-blind crossover study.
      After an initial three week placebo run-in period patients received three weeks
      of prednisolone 40 mg daily or mianserin 60-90 mg daily with an intervening three
      week placebo washout period. Full respiratory function tests, bicycle ergometry
      and 6 minute walks were performed before and after the run-in and at the end of
      each period. Psychological and functional assessments were also made at each
      visit. Prednisolone significantly increased FVC, maximum ventilation (VEmax) and
      maximum heart rate (HRmax) compared with placebo, with mean for the difference of
      0.25 l, 2.56 l.min-1 and 12 beats.min-1 respectively. FVC, maximum oxygen uptake
      (VO2max) and HRmax were also significantly increased with prednisolone compared
      with mianserin. Anxiety scores were significantly lower with prednisolone
      compared with placebo. In contrast, mianserin had no significant effects on lung
      function, exercise or psychological parameters compared with placebo. The
      improvements in ventilation, exercise and anxiety scores following treatment with
      prednisolone were not reproduced by mianserin, suggesting that the effects of
      prednisolone in COPD are unlikely to be due to alterations in mood.

PMID- 7621843
TI  - Comparison of the efficacy, tolerability and patient acceptability of once-daily
      bambuterol tablets against twice-daily controlled release salbutamol in nocturnal
      asthma. ACROBATICS Research Group.
AB  - The aim of the study was to compare the efficacy, tolerability and patient
      acceptability of bambuterol (Bambec) against controlled release (CR) salbutamol
      (Volmax) in the treatment of nocturnal asthma. One hundred and fifty two
      asthmatic patients aged 17-78 years, using > or = 800 micrograms/day of an
      inhaled steroid, with nocturnal asthma symptoms, openly received three weeks of
      bambuterol 20 mg nocte and three weeks of salbutamol CR 8 mg b.i.d. in a
      randomised, cross over sequence. Both bambuterol and salbutamol CR treatment
      produced a significant 63% decrease in the severity of baseline nocturnal asthma
      symptoms. This improved control of nocturnal asthma was reflected by significant
      improvements in baseline lung function. Both the severity and number of days of
      tremor during the first week of treatment was significantly lower with bambuterol
      than with salbutamol CR. Patients considered bambuterol to cause less shakiness
      and treatment preference was bambuterol 49%, salbutamol CR 36%, no preference
      15%. The predominant reason for patient treatment preference was control of
      asthma symptoms, however a significant sub-group of patients (27%) chose
      bambuterol because of fewer adverse effects compared to 11% choosing salbutamol
      CR. Fifty six percent of patients preferred taking their medication once-daily
      and 7% preferred twice-daily. This study shows that both bambuterol and
      salbutamol CR are equally effective treatments for nocturnal asthma in patients
      already receiving inhaled steroid. The most important factor in terms of patient
      treatment acceptability appears to be control of symptoms. Sub-groups of patients
      may chose bambuterol due to its better adverse effect profile and once-daily
      regimen.

PMID- 7621842
TI  - Oral clonidine in patients with asthma: no significant effect on airway
      reactivity.
AB  - Fifteen patients with asthma were randomized into a double-blind, placebo
      controlled, crossover trial evaluating whether clonidine increased airway
      resistance. After meeting entry criteria [demonstration of 20% improvement in any
      two of the following pulmonary function tests after bronchodilator therapy: FVC,
      FEV1, or forced expiratory flow over the mid-50% of the vital capacity(FEF(25
      75)], patients were evaluated on two subsequent visits, receiving sequential
      doses of clonidine 0.1 mg (maximum cumulative dose 0.3 mg) or placebo in a random
      fashion. They returned to clinic after a 36-48 hour washout period at which time
      they received the opposite treatment. The end points were three doses of
      clonidine or placebo, decrease in blood pressure to < or = 90 mm mercury
      systolic, and/or < 70 mm mercury diastolic, or a 20% fall in FEV1. Airway
      reactivity was proved utilizing methacholine on each clinic visit, and blood
      pressures were monitored continuously during the study period. There were no
      significant differences in the provocative concentrations of methacholine
      inducing a 20% fall in FEV1 (PD20) between baseline (1.92), clonidine (1.10), and
      placebo (1.69). (Numbers in parentheses indicate PD20 values in cumulative dose
      units).

PMID- 7621844
TI  - Muscle cramps and elevated serum creatine phosphokinase levels induced by beta
      adrenoceptor blockers.
AB  - We have assessed the propensity of beta-adrenoceptor blockers to cause muscle
      cramps and to raise the serum creatine phosphokinase (CPK) level in 78 patients
      with essential hypertension. After a control period, a beta-adrenoceptor blocker
      without intrinsic sympathomimetic activity (ISA; propranolol, metoprolol or
      arotinolol) was administered for three months. Thereafter, the patients were
      randomised to receive a beta-adrenoceptor blocker with ISA (pindolol or
      carteolol) for three months or a beta-adrenoceptor blocker without ISA for a
      further three months. This pattern was continued until all beta-adrenoceptor
      blockers had been given. At the end of each period, CPK and CPK-MB levels were
      measured. Of the 78 subjects, muscle cramps occurred in 27 during treatment with
      pindolol and 32 during treatment with carteolol. No complaints were made by
      subjects treated with propranolol and arotinolol, but muscle cramps were reported
      in 2 treated with metoprolol. While muscle cramps were caused both by pindolol
      and carteolol in 16 subjects, they were caused by either of these drugs in the
      remainder of the subjects. Muscle cramp occurred mainly in the calves when the
      patients were in bed at night. Serum CPK and CPK-MB levels increased
      significantly during treatment with pindolol (control period vs pindolol, CPK =
      96 vs 133 IU.ml-1, CPK-MB = 14 vs 18 IU.ml-1) or carteolol (CPK = 117 IU.ml-1,
      CPK-MB = 18 IU.ml-1) while the levels during treatment with propranolol,
      arotinolol and metoprolol did not change from those in the control
      period.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7621845
TI  - Inhibitory effects of antiparasitic drugs on cytochrome P450 2D6.
AB  - The interaction of antiparasitic drugs with the polymorphic cytochrome P450 2D6
      was studied in human liver microsomes. Of ten different drugs tested, three
      quinolines, oxamniquine, primaquine and chloroquine inhibited microsomal CYP2D6
      catalysed formation of 1'hydroxybufuralol at concentrations that might have
      clinical consequences in drug use. These drugs inhibited competitively bufuralol
      metabolism with Ki values of 22, 23 and 15 microM, respectively, indicative of
      high affinity for the CYP2D6-active site. The results imply that oxamniquine,
      primaquine and chloroquine could be substrates of cytochrome P4502 D6 or that
      they are potent non-substrate inhibitors of the enzyme similar to quinidine. In
      either case, the inhibition of CYP2D6 by these agents could lead to interference
      with in vivo population-phenotyping procedures in the tropical regions where
      treatment with the drugs is common.

PMID- 7621846
TI  - Aminoglycosides: single or multiple daily dosing? A meta-analysis on efficacy and
      safety.
AB  - A number of randomised studies indicate that a single high dose of aminoglycoside
      every 24 h may be more efficient and less toxic than the same dose divided into
      multiple daily doses. In the meta-analysis of 16 studies described here, which
      included more than 1200 patients, the relative chance (i.e. the relative risk,
      RR) of cure of the single-dose regime compared with the multiple-dose regime was
      1.027, indicating that the single daily dose regime had a 2.7% higher cure rate
      (NS). The RR of avoiding nephrotoxicity was 1.001 (NS) and the RR of avoiding
      ototoxicity was 1.001 (NS). It is concluded that there is no difference
      concerning efficacy and safety between single-dose and multiple-dose regimes for
      administration of aminoglycosides.

PMID- 7621847
TI  - Prolongation of the PQ interval as a measure of therapeutic inequivalence between
      two formulations of diltiazem.
AB  - We studied the use of atrioventricular (AV) conduction time to assess the
      therapeutic equivalence of two diltiazem formulations in 20 volunteers in a
      double-blind, cross-over trial. ECG recording was carried out before and at
      several intervals after drug administration, and prolongation of the PQ interval
      (delta PQ) was taken as a pharmacodynamic response. In addition, diltiazem plasma
      concentrations were determined in 8 subjects. The effect of diltiazem increased
      proportionally with the plasma concentration and could be detected up to 10 h
      after administration. The area under the effect-time curve (AUEC(0-10)), the peak
      effect (Emax), and the effect mean residence time (MRTE) showed significant
      differences. In contrast to the pharmacodynamics, the pharmacokinetic profiles of
      diltiazem do not vary to the same extent. We conclude that the formulations are
      therapeutically different. Furthermore, at the administered dose, delta PQ
      appears to be a sensitive measure for assessing the electrophysiological
      properties of diltiazem.

PMID- 7621848
TI  - Estimation of the absolute bioavailability of flecainide using stable isotope
      technique.
AB  - Data on the absolute bioavailability of flecainide are controversial. We have
      investigated whether differences in metabolic clearances and/or the absorption
      profile might be responsible for the variability in its absolute bioavailability.
      Six subjects with a wide range of flecainide metabolic clearances (85-407 ml.min
      1) simultaneously received the drug by the IV and oral routes; the oral dose was
      labelled with deuterium. Besides estimation of absolute bioavailability, this
      design permitted assessment of metabolic clearance after IV and oral
      administration, and absorption could be assessed from the urinary excretion of
      labelled and unlabelled drug and metabolites. The absolute bioavailability of
      flecainide ranged from 79.9 to 101.1% (mean 93.6%). The absorption was 86.1 to
      101.3% (mean 93.2%). The data indicate that the variable bioavailability of
      flecainide is due both to metabolism and absorption. The study highlights the
      potential of stable isotope technique in the investigation of such issues.

PMID- 7621849
TI  - Elimination of amrinone during continuous veno-venous haemofiltration after
      cardiac surgery.
AB  - We studied the elimination of amrinone during continuous veno-venous
      haemofiltration (CVVHF) in three anuric patients after cardiac surgery. The
      patients had developed low cardiac output followed by acute prerenal failure.
      Plasma amrinone levels measured by HPLC were fitted to a two-compartment model.
      We found significant amrinone clearance, with a mean sieving coefficient (S) of
      0.44%, which correlates with the protein-unbound, pharmacologically effective
      fraction of amrinone. The AUC of the arterial plasma concentration-time curve was
      decreased by 49.8%. All pharmacokinetic parameters showed wide interindividual
      variation. To ensure the therapeutic effect of amrinone and to avoid toxic
      adverse effects monitoring of plasma amrinone levels is necessary.

PMID- 7621850
TI  - Interaction between valproate formulation and phenytoin concentrations.
AB  - Changes in phenytoin concentrations caused by switching valproate formulations
      with different absorption rates were retrospectively investigated in eleven
      epileptic patients receiving treatment with both drugs. Total plasma phenytoin
      concentrations were measured before and after a standard tablet of valproate was
      replaced by the same dose as a slow-release tablet. The mean plasma phenytoin
      level rose significantly from 14.4 to 18.7 micrograms.ml-1. Nine of eleven
      patients had markedly increased phenytoin levels (by 21 to 72%), and two
      developed toxic symptoms. The results indicate that changing valproate
      formulations can cause major alterations in the plasma concentration of co
      administered phenytoin.

PMID- 7621852
TI  - Radiation recall in a patient with breast cancer treated for tuberculosis.

PMID- 7621851
TI  - Paracetamol disposition in Thai patients during and after treatment of falciparum
      malaria.
AB  - Investigations in animals have suggested that conjugation of paracetamol may be
      reduced in malaria. We have measured plasma concentrations and the urinary
      excretion of paracetamol and its phase II metabolites in eight Thai patients
      during uncomplicated falciparum malaria and in convalescence, following a 1000 mg
      single oral dose. The apparent oral clearance (Malaria, 3.6; Convalescence, 3.9;
      ml.min-1.kg-1), the elimination half-life (Malaria, 3.8; Convalescence, 3.7 h)
      and apparent volume of distribution (Malaria, 1.2; Convalescence, 1.2; l.kg-1) of
      paracetamol were similar during malaria and convalescence. In addition, the
      urinary excretion of paracetamol and its major phase II metabolites and their
      formation clearances from paracetamol were not significantly different between
      the two study phases. These data show that clinical malaria infection has no
      effect on the conjugation of paracetamol in man.

PMID- 7621853
TI  - The acetylation phenotype: does it contribute to the non-linearity of the
      metabolite pharmacokinetics of metamizol?

PMID- 7621854
TI  - Pulmonary hypertension and dexfenfluramine.
AB  - Appetite suppressants, including aminorex and fenfluramine, have been associated
      with pulmonary hypertension ever since the well-known outbreak of primary
      pulmonary hypertension in Europe after treatment with aminorex. The usage of a
      new anorectic agent, dexfenfluramine, has recently increased dramatically in
      developed countries. We report 2 new cases of lethal pulmonary hypertension
      associated with the use of dexfenfluramine.

PMID- 7621855
TI  - Commentary on interactions between 6-mercaptopurine therapy and thiopurine-methyl
      transferase (TPMT) activity.

PMID- 7621856
TI  - Androgenic anabolic steroid use among male adolescents in Falkenberg.
AB  - Recent reports show that androgenic anabolic steroids are used by many teenagers,
      not as a deliberate attempt to give them strength, better athletic performance,
      etc., but to improve their looks. The so-called macho cult among young boys
      tempts them into using androgenic anabolic steroids to give them bigger muscles
      and a more powerful appearance. This study was undertaken to investigate the
      prevalence of androgenic anabolic steroid use among teenagers in a small town and
      to create a platform for future work with the aim of decreasing the misuse of
      these drugs. In Falkenberg, a town in the county of Halland in the west of
      Sweden, the pupils at two high schools were investigated by means of an anonymous
      multiple-choice questionnaire. A total of 1383 students (688 males and 695
      females) aged 14-19 years participated in the study, giving a participation rate
      of 96%. The number of answers completed was 99%. The use of androgenic anabolic
      steroids is a reality among male teenagers in Falkenberg, with 5.8% of them using
      the drugs. Among 15- to 16-year-old boys misuse of these drugs is as high as 10%,
      and of these 50% (5.0% of total) also inject ampoules of the drugs. This
      prevalence is alarming since the adverse effects of androgenic anabolic steroids
      are more serious in teenagers. Serious action must be taken to inform teenagers
      of the consequences of misusing drugs.

PMID- 7621857
TI  - Immunodominance with progenitor B cell diversity in the neutralizing antibody
      repertoire to influenza infection.
AB  - We report striking immunodominance in the neutralizing antibody responses of
      major histocompatibility complex congenic mice to natural infection with
      influenza virus (H3N2 subtype), as deduced by sequencing the hemagglutinin (HA)
      genes of monoclonal antibody (mAb)-selected mutant viruses. A majority of mAb,
      established from individual BALB/c (H-2d) mice, select mutant viruses containing
      the same single amino acid substitution in the membrane distal ecto-domain, HA1
      198 A-->E, whereas changes at either HA1 158 G-->E or HA1 198 A-->E are selected
      for by mAb from BALB.K (H-2k) donors. The structural basis for immunodominance,
      and potential diversity of progenitor B cells, was investigated by sequence
      analysis of H and L chain gene rearrangements in mAb specific for HA1 158 or HA1
      198. No correlation was found between antibody specificity and VH or VL gene
      usage, and a minimum of three to six progenitor cells contributed to the
      individual's repertoire for a single antigenic site. However, in a further
      analysis of the HA1 158-specific antibody response of CBA/Ca (H-2k) donors, there
      was highly restricted light chain gene usage. Focusing of the immune repertoire
      to limited regions of the HA molecule during a primary viral infection may be a
      significant factor in immune pressure for antigenic variation, particularly since
      there is no evident restriction in the antibody response to immunization.

PMID- 7621858
TI  - The self antigen heme evades immune recognition by sequestration in some
      hemoproteins.
AB  - Heme is a non-protein autoantigen which is ubiquitous in vivo, primarily
      complexed in various hemoproteins or bound to specialized carrier molecules.
      Nevertheless, heme is able to stimulate a high frequency of CD4+, class II
      restricted T cells, freshly explanted from unprimed mice, to proliferate in
      vitro. In this study, we show that heme incorporated into various species of
      mammalian cytochrome c (cyt c), including murine cyt c, represents a facultative
      cryptic determinant, able to be recalled only at high doses of native cyt c. By
      contrast, avian cyt c is of comparable antigenicity to free heme. Artificially
      denatured carboxymethylated (CM) mammalian cyt c exhibited greatly increased
      antigenicity, comparable to that of heme and avian cyt c, indicating that the
      crypticity of heme in native mammalian cyt c is due to the resistance of the
      native conformation of this molecule to antigen processing within murine antigen
      presenting cells. Thus, tolerance to the heme group of at least some
      hemoproteins, may be maintained by the crypticity of the heme, rather than by
      deletion of heme-reactive T cells. Given the high frequency of heme-reactive T
      cells in unprimed mice, these findings suggest that heme may become an important
      modulator during an inflammatory response.

PMID- 7621859
TI  - Destructive proteolysis by cysteine proteases in antigen presentation of
      ovalbumin.
AB  - Most native antigens require digestion by acidic proteases in order to be
      recognized in the context of major histocompatibility complex class II by T
      helper cells (Th). We have studied the roles of three different acidic proteases,
      cathepsin D, cathepsin B and cathepsin L, in the processing of ovalbumin (OVA)
      for presentation in the context of I-Ad. We report that digestion of OVA in vitro
      with the aspartyl protease cathepsin D generates the epitope OVA322-336, which is
      recognized by I-Ad-restricted OVA-specific Th in the presence of paraformaldehyde
      fixed antigen-presenting cells (APC). In contrast, digestion of OVA with the
      cysteine proteases cathepsin B and L not only failed to generate an epitope, but
      also destroyed OVA322-336. In the presence of fixed APC expressing I-Ad. OVA322
      336 was protected from destructive proteolysis by cathepsin L. These results
      illustrate the dependence of epitope selection on the intracellular proteolytic
      environment in APC, and suggest that mechanisms must exist for protection of
      epitopes from destructive proteolysis in the processing compartments.

PMID- 7621860
TI  - Phosphatidylinositol 4,5-bisphosphate hydrolysis accompanies T cell receptor
      induced apoptosis of murine thymocytes within the thymus.
AB  - Regulation of the development of thymocytes into mature T cells within the thymus
      is now known to involve antigen-induced deletion, by apoptosis, of potentially
      autoreactive thymocytes, and it can be mimicked either by stimulating the T cell
      receptor (TcR) complex by monoclonal antibody (mAb) or by ionophore-induced
      elevation of cytosolic [Ca2+]. To identify signaling pathways employed by the TcR
      complex of immature thymocytes, we examined the effects of anti-CD3 and anti-TcR
      beta constant (c) region mAb, staphylococcal enterotoxin B (SEB) and
      pharmacological agents on the generation of inositol phosphates through
      hydrolysis of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] both in
      cultured fetal mouse thymic lobes and in the CD4+CD8+ immature thymocyte cell
      line, TM10G. Stimulation of the TcR complex with anti-CD3 mAb provoked an
      accumulation of inositol phosphates diagnostic of the occurrence of receptor
      stimulated phosphoinositidase C (PLC) activation. Anti-TcRC beta mAb and SEB
      provoked smaller but similar responses. The PLC activation evoked by anti-CD3 mAb
      was suppressed by inhibitors of receptor tyrosine kinases and was unmodified by
      protein kinase C activation or elevation of cytosolic [Ca2+]. It thus appears
      that apoptosis triggered by TcR stimulation is associated with PLC activation by
      a receptor-regulated tyrosine kinase. Treatment of thymic lobes or TM10G cells
      with fluoroaluminate provoked apoptosis of a wider range of thymocyte subtypes
      and such stimulation also provoked an accumulation of inositol phosphates. The
      responses to fluoroaluminate were not prevented by inhibitors of tyrosine
      kinases, suggesting that unidentified GTP-binding proteins which couple to PLC
      activation may also be capable of initiating apoptosis by a route independent of
      the TcR. These results, when considered alongside previous studies of mature T
      cells, indicate that stimulation of immature thymocytes or of mature T cells
      through their TcR complex activates the PLC-catalyzed PtdIns(4,5)P2 hydrolysis
      signaling pathway, and thus that this signaling pathway may be implicated both in
      provoking apoptosis in immature T cells and in initiating proliferation in mature
      T cells.

PMID- 7621861
TI  - Induction of the increased Fyn kinase activity in anergic T helper type 1 clones
      requires calcium and protein synthesis and is sensitive to cyclosporin A.
AB  - Several alterations in T cell receptor-associated signal transduction have been
      observed following induction of anergy of T helper type 1 (Th1) clones, including
      a modified intracellular free calcium ([Ca2+]i) response and increased kinase
      activity associated with the protein tyrosine kinase p59fyn. In the current
      study, we demonstrate that, although the kinetics of acquisition of both of these
      signaling alterations correlated with the generation of anergy, a normal calcium
      response returned within 48 h after removal from the anergizing stimulus, whereas
      the increased p59fyn activity persisted and the cells remained hyporesponsive.
      Generation of both the anergic state and the increased p59fyn activity was
      prevented in the presence of calcium-free medium, cycloheximide (CHX), or
      cyclosporin A (CsA), and could be mimicked by the calcium ionophore ionomycin. In
      contrast, the altered calcium response was inhibited by stimulation in the
      presence of calcium-free medium or CsA, but not CHX. Thus, surprisingly, these
      data suggest that a chronic elevation of [Ca2+]i is proximal to and necessary for
      the increase in p59fyn-associated kinase activity observed in anergic Th1 clones.
      Increased p59fyn activity, but not the altered calcium response, correlates with
      maintenance of the anergic state.

PMID- 7621862
TI  - The influence of invariant chain on the positive selection of single T cell
      receptor specificities.
AB  - The appearance of peptide-loaded major histocompatibility complex (MHC) class II
      molecules at the cell surface depends critically on the invariant chain (Ii). We
      have studied the influence of Ii on the positive selection of CD4+ T cells,
      mediated by class II molecules expressed on thymic stromal cells. Invariant chain
      deficient mice (Iio) were crossed with different T cell receptor (TcR) transgenic
      strains and the emergence of mature CD4 single-positive thymocytes measured in
      Iio/TcR transgenic offspring. Positive selection was nearly absent in Iio/2B4
      mice, which display receptors specific for a moth cytochrome c (MCC) peptide in
      the context of Ek. In addition, no T cell response was elicited when
      nontransgenic Iio animals were injected with this peptide, even though antigen
      presenting cells (APC) from such mice were perfectly capable of presenting it,
      suggesting that selection of the entire anti-MCC 88-103 repertoire depends on Ii.
      Positive selection also appeared strongly reduced in another line of Iio/TcR
      transgenic mice (Iio/BDC2.5). However, in sharp contrast, a third line (Iio/3A9)
      exhibited almost normal positive selection of thymocytes displaying the transgene
      encoded receptor. These thymocytes were exported to the periphery: peripheral T
      cells could respond normally to the appropriate peptide in vitro. The most likely
      interpretation of these findings is that selection of most CD4+ T cells depends
      on MHC class II complexes loaded with peptide in an Ii-dependent pathway, but
      some can be selected on class II complexes that are either loaded along an
      alternative, Ii-independent, route or are empty. This is consistent with the
      involvement of peptide in positive selection of CD4+ T cells, for which there
      exists little prior evidence.

PMID- 7621863
TI  - Apoptosis of ileal Peyer's patch B cells is increased by glucocorticoids or anti
      immunoglobulin antibodies.
AB  - The ileal Peyer's patch (PP) in sheep plays a central role in the development and
      production of B cells. Associated with a tremendous amount of B cell
      proliferation in this site is the extensive diversification of the Ig repertoire
      by somatic hypermutation. Very few (< 5%) of the B cells produced in the ileal PP
      differentiate and emigrate; instead, the vast majority of these cells soon die,
      and we have previously shown that death is associated with apoptosis. When placed
      in culture, ileal PP B cells die rapidly by apoptosis, such that after 24 h, 60
      +/- 1% of DNA is fragmented. Here, we show that the extent of this spontaneous B
      cell apoptosis in culture, as quantitated by DNA fragmentation, was significantly
      increased in a dose-dependent manner by the glucocorticoids hydrocortisone or
      dexamethasone. Furthermore, treatment of lambs with 2-2.5 mg/kg of dexamethasone
      resulted in a marked increase in the number of apoptotic cells in the ileal PP
      and an increase in ileal PP B cell DNA fragmentation to 20 +/- 6%, compared with
      2.4 +/- 0.1% in untreated lambs. Anti-immunoglobulin (Ig) antibodies also
      increased the extent of DNA fragmentation in cultured ileal PP B cells. After 24
      or 48 h of culture with anti-Ig (PIg47A), DNA fragmentation was 74 +/- 2% and 75
      +/- 3%, respectively. Ileal PP B cells are rescued from apoptosis by agents that
      activate protein kinase C and increase cytosolic Ca2+, and here we show that this
      treatment also results in apoptotic rescue in the presence of dexamethasone or
      anti-Ig. We speculate that the apoptosis of ileal PP B cells in situ may be
      modulated by glucocorticoids and by the cross-linking of surface Ig. Apoptosis,
      induced by a signal through surface Ig, may be an important mechanism in the
      deletion of self-reactive B cells during the expansion of the Ig repertoire in
      the ileal PP.

PMID- 7621864
TI  - Intra- and extra-thymic expression of the pre-T cell receptor alpha gene.
AB  - We have analyzed pre-T cell receptor alpha (pT alpha) gene expression in cells
      from various anatomical sites to investigate the lineage specificity of pT alpha
      RNA as well as its presence in pro-T cells and in sites of extrathymic T cell
      development. pT alpha RNA is found in precursors of alpha beta T cells but is
      absent from mature alpha beta T cells as well as T cells that express the gamma
      delta T cell receptor on the cell surface. pT alpha expression is exquisitely T
      lineage specific in that mature and immature B cells, myeloid cells, NK cells and
      pluripotent stem cells are pT alpha negative. On the other hand, pT alpha
      expression is found in pro-T cells outside the thymus as well as in intra- and
      extra-thymic sites of T cell development. The latter finding is consistent with
      the notion that early steps of T cell development within and outside the thymus
      may be similar.

PMID- 7621866
TI  - Preferential recognition of specific DNA motifs by anti-double-stranded DNA
      autoantibodies.
AB  - Although antibodies (Ab) specific for double-stranded (ds) DNA are thought to be
      involved in the etiopathogenesis of systemic lupus erythematosus (SLE), the fine
      structure of their DNA targets remains elusive. We have adapted a polymerase
      chain reaction (PCR)-assisted immunoprecipitation method to define the binding
      sites in DNA sequences recognized by high affinity anti-dsDNA Ab of SLE patients.
      SLE sera were used to bind templates from a pool of double-stranded
      oligonucleotides (ON). A central part of 20 base-pair random sequence was flanked
      by restriction endonuclease recognition sites and sequences complementary to
      predefined PCR primers. Immunoselected ON were precipitated, isolated from the
      immune complexes and then subjected to a further immunoprecipitation step after
      amplification by PCR. After five cycles of immunoprecipitation and PCR, the
      resulting ON were cloned. Sequence analysis revealed that sera from SLE patients
      and two human monoclonal anti-dsDNA Ab obtained from SLE patients preferentially
      select sequences expected to form non-B-DNA structures. Inhibition studies of the
      Farr assay confirmed the increased affinity of the selected epitopes for anti-DNA
      Ab as compared to random B-DNA.

PMID- 7621865
TI  - Rearrangement of upstream DH and VH genes to a rearranged immunoglobulin variable
      region gene inserted into the DQ52-JH region of the immunoglobulin heavy chain
      locus.
AB  - We investigated gene rearrangements in the mutant IgH locus of a mouse strain
      generated by insertion of a rearranged heavy chain variable region gene (VT15)
      into the DQ52-JH region through gene targeting. In more than half of the B cells
      of heterozygous mutant mice, the mutant IgH locus was silenced by the
      rearrangement of an endogenous DH or DH and VH gene to the inserted VT15 gene. In
      these cases, a functional VHDHJH gene was present on the wild-type allele. The
      silencing rearrangement appeared to be mediated by recombination signal sequence
      (RSS)-like elements present in the "recipient" VT15 gene. Among the many such
      elements on the inserted VT15 gene, which apparently met the requirement for an
      RSS with respect to nucleotide sequence, only two were observed in the actual
      rearrangements. This indicates that targeting of the recombination machinery
      involves sequences in addition to the RSS motifs as they have been characterized
      so far. In homozygous mutant mice, most B cells appeared to carry the intact VT15
      gene on both mutant IgH alleles, although single-cell polymerase chain reaction
      revealed that silencing rearrangements occurred frequently in B cell progenitors
      in the bone marrow. This observation indicates that once silencing rearrangements
      are initiated in a cell, they involve both VT15 genes in most cases, reminiscent
      of normal DH-JH rearrangement. B cells which did not initiate such rearrangements
      develop to populate the peripheral B cell compartment.

PMID- 7621868
TI  - Germinal-center cell proliferation in response to T-independent antigens: a
      stathmokinetic, morphometric and immunohistochemical study in vivo.
AB  - Although the nature of the germinal center reaction during responses to T
      dependent antigens has been well documented, much less is known regarding the
      relationship between germinal centers and T-independent antigens. In this study,
      germinal-center cell proliferation was determined at specific time points in
      spleens of C3H/HeN mice following immunization with either the type-1, T
      independent antigen dinitrophenol-lipopolysaccharide (DNP-LPS), or the type-2, T
      independent antigen DNP-Ficoll. A stathmokinetic technique was employed to assess
      proliferation in terms of germinal center cell birth rate and morphometry was
      used to measure actual growth and regression of the germinal center cell
      population. An estimate of the absolute rate of germinal-center (GC) cell
      proliferation was derived from these two values. In addition,
      immunohistochemistry was performed to correlate changes in GC cell proliferation
      with the presence or absence of antigen within GC. Following immunization with
      both antigens, there was an initial reduction of proliferation within pre
      existing germinal centers which manifested as either GC dissociation (DNP-LPS) or
      a suppression of birth rates (DNP-Ficoll). This was followed by a period of
      increased GC cell proliferation in animals immunized with DNP-LPS, but not in
      those exposed to DNP-Ficoll. GC cell proliferation was then measured in mice
      treated with cyclosporin A from 1 day before to 2 days after immunization with
      DNP-LPS. In these animals, the expected increase in GC cell birth rates did not
      take place. Immunohistochemistry showed that DNP-Ficoll and DNP-LPS were present
      in GC from 1 day after immunization until the end of the experiment on day 7.
      Treatment with cyclosporin A did not affect the deposition of DNP-LPS in GC.
      These results show that only some T-independent antigens are able to stimulate GC
      cell proliferation, and we propose that this is related to their ability to
      recruit precursors of GC B cells into the GC reaction. In addition, the results
      indicate that GC proliferation seen in response to a so-called T-independent
      antigen is at least partly driven by T cell-derived cytokines.

PMID- 7621867
TI  - Non random activation of endogenous interleukin-2, (IL-2), IL-2 receptor alpha
      and IL-2 receptor beta genes after transfection of mouse fibroblasts with a cDNA
      for the alpha chain of the human IL-2 receptor.
AB  - Mouse fibroblasts do not ordinarily express components for the interleukin-2
      receptor (IL-2R alpha, beta, and gamma). An analysis of these cells by reverse
      transcription followed by polymerase chain reaction, however, indicates the
      presence of transcripts specific for the IL-2R beta and gamma genes. Transfection
      of the cDNA for the alpha chain of the human IL-2R into LTK- mouse fibroblast
      cell line (L3 cells) leads, in long-term cultures, to the formation of
      transcripts of endogenous mouse IL-2, IL-2R alpha and beta genes, as detected by
      Northern blotting. Based upon the results of the binding of 125I-labeled IL-2 to
      the transfected cells, three IL-2-binding proteins of 55 kDa, 65 kDa and 75 kDa
      were expressed by the transfected cells. The 65-kDa and 75-kDa proteins bound IL
      2 in the presence of monoclonal antibodies for the IL-2R alpha chain. These
      polypeptides assembled to form high-affinity IL-2R, as shown by Scatchard binding
      analyses. The receptors were functionally active, since the expression of H-2k
      major histocompatibility complex antigens on the surface membranes of L3 cells
      was enhanced by exposing the cells to IL-2. Activation of the IL-2 gene was also
      observed in long-term cultures of L alpha beta cells, another LTK- transfectant
      expressing the human IL-2R alpha chain. This type of gene activation was not
      observed in LTK- fibroblasts transfected with cDNA for human IL-2 or IL-2R beta
      genes. In L3 and L alpha beta cells, transcription of the endogenous IL-2 gene
      was suppressed by cyclosporin A and enhanced by cycloheximide. These data may
      have implications for gene therapy of cancer cells.

PMID- 7621869
TI  - Peripheral deletion of autoreactive CD8+ T cells in transgenic mice expressing H
      2Kb in the liver.
AB  - The response of T cells specific for liver antigens was examined in transgenic
      mice expressing the allogeneic major histocompatibility complex class I molecule
      H-2Kb (Kb) under the control of the sheep metallothionein promoter (Met-Kb mice).
      To follow the fate of Kb-specific T cells, and to prevent any aberrant thymic
      expression of the Kb transgene, the mice were thymectomized, lethally irradiated,
      protected with bone marrow cells from transgenic mice expressing in their T cells
      a Kb-specific T cell receptor identifiable by a clonotypic antibody, and given
      syngeneic non-transgenic thymus grafts. Although Kb-specific CD8+ T cells were
      produced in the thymus grafts of these manipulated Met-Kb mice, only small
      numbers of such cells could be detected in the spleen and lymph nodes. The
      livers, however, showed signs of damage and were heavily infiltrated by actively
      dividing CD8+ T cells. We provide strong evidence that the hepatocytes, not
      generally regarded as antigen-presenting cells, activated the Kb-specific CD8+ T
      cells and that these disappeared after a vigorous autoimmune response that
      resulted in deletion.

PMID- 7621871
TI  - A myelin oligodendrocyte glycoprotein peptide induces typical chronic
      experimental autoimmune encephalomyelitis in H-2b mice: fine specificity and T
      cell receptor V beta expression of encephalitogenic T cells.
AB  - A predominant response to myelin oligodendrocyte glycoprotein (MOG) was recently
      observed in patients with multiple sclerosis (MS). To study the possible
      pathogenic role of T cell response to MOG in MS, we have investigated the
      encephalitogenic potential of MOG. Synthetic MOG peptides, pMOG 1-21, 35-55, 67
      87, 104-117 and 202-218, representing predicted T cell epitopes, were injected
      into C57BL/6J and C3H.SW (H-2b) mice. The mice developed significant specific T
      cell responses to pMOG 1-21, pMOG 35-55 and pMOG 104-117. However, pMOG 35-55 was
      the only MOG peptide which could induce neurological impairment. The highly
      reproducible disease was chronic, with ascending paralysis and neuropathology
      comparable with those observed in experimental autoimmune encephalomyelitis (EAE)
      induced by myelin basic protein or proteolipid protein, except that in H-2b mice
      the disease was consistently non-remitting. These features differ markedly from
      those which we recently observed in PL (H-2u) mice with pMOG 35-55-induced
      disease. In PL mice, pMOG 35-55-induces atypical chronic relapsing EAE, the
      expression and progression of which are unpredictable. Hence, in different mouse
      strains, the same MOG peptide can induce typical EAE characterized by ascending
      paralysis, or atypical EAE with unpredictable clinical signs. pMOG 35-55-specific
      T cells from H-2b mice recognized an epitope within amino acids 40-55 of the MOG
      molecule, and pMOG 40-55-reactive T cell lines were encephalitogenic upon
      transfer into syngeneic recipients. The encephalitogenic pMOG 35-55-reactive
      C57BL/6J T cell lines expressed V beta 1, V beta 6, V beta 8, V beta 14 and V
      beta 15 gene segments, and the pMOG 35-55-reactive C3H.SW T cell lines expressed
      V beta 1, V beta 2, V beta 6, V beta 8, V beta 10, V beta 14, and V beta 15 gene
      segments. However, in both mouse strains, the utilization of the V beta 8 gene
      product was predominant (40-43%). The highly reproducible encephalitogenic
      activity of pMOG 35-55 strongly suggests a pathogenic role for T cell reactivity
      to MOG in MS and supports the possibility that MOG may also be a primary target
      antigen in the disease.

PMID- 7621870
TI  - Spontaneous apoptosis of dendritic cells is efficiently inhibited by TRAP (CD40
      ligand) and TNF-alpha, but strongly enhanced by interleukin-10.
AB  - In the lymphoid tissues, adaptive immune responses are initiated by the
      interaction of interdigitating dendritic cells (IDC) with naive T cells. To
      understand this interplay better, we used mature Langerhans cells (mLC),
      migrating from human epidermis, as the correlate of IDC ex vivo to evaluate the
      different effects of tumor necrosis factor (TNF)-alpha. TNF-related activation
      protein (TRAP; CD40-ligand) and interleukin-10 (IL-10) on induction or prevention
      of apoptotic cell death in these cells. Spontaneous decrease of mLC viability in
      culture was due to apoptosis, as determined by the appearance of typical
      morphological changes such as dilatation of the endoplasmic reticulum (ER),
      chromatin condensation and membrane blebbing. IL-10 strongly reduced mLC
      viability, whereas TRAP and TNF-alpha facilitated the survival of mLC.
      Spontaneous DNA fragmentation was detectable after 24 h in culture. IL-10 led to
      an earlier onset of DNA fragmentation, whereas TRAP and TNF-alpha delayed
      internucleosomal DNA cleavage. We found that IL-10-treated mLC were readily
      ingested and removed by macrophages. TNF-alpha and TRAP, in contrast, reduced
      engulfment of mLC by macrophages. Interestingly, IL-10, even at low
      concentrations, reverted the effects of TNF-alpha and TRAP in inhibiting mLC
      apoptosis. Furthermore, IL-10 led to the down-regulation of various surface
      antigens, especially of CD86 and CD54, whereas TNF-alpha and TRAP enhanced the
      expression of MHC class I and II antigens and of the accessory molecules CD40,
      CD54, CD80 and CD86. Taken together, these results show that mLC spontaneously
      undergo apoptosis in culture and that the progression of mLC to apoptosis is
      inhibited by TRAP and TNF-alpha, but accelerated by IL-10.

PMID- 7621872
TI  - Are CD8 T cells involved in control of African trypanosomiasis in a natural host
      environment?
AB  - Murine models have suggested that CD8 T cells might play a major parasite
      promoting role in African trypanosomiasis. To assess the role of these cells in a
      natural host environment, we have depleted CD8 cells from Boran cattle in vivo
      and subsequently infected these animals with Trypanosoma congolense by tsetse fly
      challenge. Following administration of a mouse monoclonal anti-bovine CD8
      antibody, we have been able to achieve a depletion of more than 99.9% in
      peripheral blood, spleen, prescapular lymph nodes, prefemoral lymph nodes,
      mesenteric lymph nodes and Peyer's patches. Depletion could be maintained over a
      4-5-week infection period. Despite the almost total absence of CD8 cells, no
      effect whatsoever was observed on parasitemia. In addition, anemia, which is the
      main factor determining the mean survival time in cattle was not affected by the
      CD8 depletion.

PMID- 7621873
TI  - Self-reactive anti-class II T helper type 2 cell lines derived from gold salt
      injected rats trigger B cell polycolonal activation and transfer autoimmunity in
      CD8-depleted normal syngeneic recipients.
AB  - Brown Norway (BN) rats given gold salts develop an autoimmune syndrome with an
      immune complex-type glomerulonephritis in the context of a polyclonal B cell
      activation that was suspected to be due to the emergence of anti-self major
      histocompatibility complex (MHC) class II T cells. In the present study, six anti
      self MHC class II T cell lines have been derived from six gold salt-treated rats
      by repeated stimulations with normal syngeneic MHC class II-bearing cells. The T
      cell lines proliferated in the presence of self MHC class II-positive B cell
      enriched or B cell-depleted cells and the proliferation was inhibited by
      preincubating stimulator cells with an anti-IA monoclonal antibody. The T cell
      lines produced interleukin (IL)-4 only or IL-4 and some interferon (IFN)-gamma
      and could, therefore, be considered as T helper type 2 (Th2) and Th0 cells,
      respectively. They triggered normal syngeneic B cells to produce in vitro IgE,
      anti-DNA, anti-laminin and anti-2,4-6-trinitrophenol antibodies through, at least
      in part, cognate interactions. More interestingly, these lines when transferred
      into normal BN rats induced an autoimmune syndrome similar to or even more severe
      than the one observed in the active gold model, provided the recipients were CD8
      depleted. These manifestations included a dramatic increase in serum IgE
      concentration and the production of anti-DNA and anti-laminin antibodies. In
      addition, all recipients displayed an autoimmune glomerulonephritis due to anti
      laminin antibodies, granular IgG deposits in the interstitium, in the vessel
      walls and along the tubular basement membranes and a severe tubulointerstitial
      nephritis with marked mononuclear cell infiltration. An anti-ovalbumin T cell
      line that produced IL-4 and low amounts of IFN-gamma was used as a control and
      did not induce autoimmunity. These results demonstrate for the first time the
      ability of autoreactive Th2 as well as Th0 cell lines to induce antibody-mediated
      autoimmunity. They also show that CD8+ cells play a crucial role in the control
      of such autoreactive cells. Finally, this work suggests that Th2 cells could
      initiate cell-mediated reactions either directly or indirectly.

PMID- 7621874
TI  - Early appearance of T cell receptor alpha beta + CD4- CD8- T cells with a skewed
      variable region repertoire after infection with Listeria monocytogenes.
AB  - We found that the number of T cell receptor (TCR) alpha beta + CD4- CD8- T cells
      increased in the peritoneal cavity on day 5 after an intraperitoneal infection
      with Listeria monocytogenes strain EGD together with TCR gamma delta + CD4- CD8-
      T cells. Thereafter, the TCR alpha beta + CD4- CD8- T cells decreased to a normal
      level by day 14. The TCR alpha beta + CD4- CD8- T cells showed an activated T
      cell phenotype (L-selectin CD44 +) and expressed CD45/B220 and interleukin-2
      receptor beta, but did not express heat stable antigen, which is expressed by the
      immature CD4- CD8- thymocytes. Furthermore, 20-30% of the TCR alpha beta + CD4-
      CD8- T cells expressed the NK1.1 natural killer cell marker. Analysis of the TCR
      V region repertoire of the TCR alpha beta + CD4- CD8- T cells induced by L.
      monocytogenes infection showed that more than 80% of the TCR alpha beta + CD4-
      CD8- T cells expressed TCR V beta 8 detected by anti-TCR V beta 8.1 and 8.2 mAb,
      and a reverse transcription-polymerase chain reaction analysis of V alpha 14
      relative to V alpha 11 expression revealed that the TCR alpha beta + CD4- CD8- T
      cells expressed a higher level of V alpha 14, which was reported to be
      preferentially expressed by TCR alpha beta + CD4- CD8- thymocytes rather than
      conventional CD4+ T cells. The TCR alpha beta + CD4- CD8-T cells showed a
      proliferative response to anti-TCR alpha beta mAb stimulation. In contrast, they
      showed no response to stimulation with either Listeria antigen or 65-kDa heat
      shock protein of Mycobacterium bovis, which do stimulate the Listeria-specific
      TCR alpha beta + CD4- CD8- T cells and the Listeria-induced TCR gamma delta + T
      cells, respectively. These results suggest that the TCR alpha beta + CD4- CD8- T
      cells may recognize a restricted set of self antigens induced by L. monocytogenes
      infection, and that they contribute to host protection at an early stage of
      infection.

PMID- 7621875
TI  - Sphingomyelin-ceramide turnover in CD28 costimulatory signaling.
AB  - When the CD28 membrane glycoprotein of T cells binds to its ligand, a signal is
      transmitted that is required for T cell receptor-induced proliferation and
      cytokine secretion: T cells are not stimulated by the CD28 signal alone. Ligation
      of CD28 initiated sphingomyelin hydrolysis and generated ceramide. Treatment of T
      cells with either exogenous sphingomyelinase or a cell-permeable ceramide
      analogue. C6-ceramide, mimicked the CD28 signal by inducing T cell proliferation
      and interleukin-2 gene transcription. Stabilization of interleukin-2 mRNA was
      also observed in C6-ceramide-treated cells. Thus, the sphingomyelin-ceramide
      pathway is a candidate for mediating the costimulatory signal.

PMID- 7621876
TI  - The role of lymphocyte subsets and adhesion molecules in T cell-dependent
      cytotoxicity mediated by CD3 and CD28 bispecific monoclonal antibodies.
AB  - The cure of human Hodgkin's tumors heterotransplanted into SCID mice can be
      achieved by two bispecific monoclonal antibodies (Bi-mAb) directed against the
      tumor-associated CD30 antigen and CD3 and CD28, respectively, and normal
      peripheral human blood T cells. We investigated the role of lymphocyte subsets
      and adhesion molecules in this Bi-mAb-mediated cytolysis. CD4+ lymphocytes were
      the most rapidly expanding subpopulation, but Bi-mAb-directed cytotoxicity was
      mediated preferentially by CD8+ lymphocytes and effector cells belonging to the
      CD45RO+ "memory" pool. Blocking of the LFA-1/ICAM-1 or CD2/LFA-3 adhesion
      pathways by mAb decreased Bi-mAb-mediated cytotoxicity. This was not due to
      inhibition of aggregate formation between Bi-mAb-coated T lymphocytes and target
      cells. Cross-linking of LFA-1 or CD2 molecules on lymphocytes prestimulated with
      Bi-mAb bound to CD3 and CD28 antigen lead to a more pronounced and prolonged rise
      in the intracellular concentration of free Ca2+. Additional CD2 cross-linking
      resulted in the tyrosine phosphorylation of distinct proteins. These findings
      indicate that adhesion molecules play a critical role and function as co
      stimulatory signals rather than as cellular contact mediators in CD3 and CD28 Bi
      mAb-stimulated T lymphocytes.

PMID- 7621877
TI  - Alpha 6 integrins participate in pro-T cell homing to the thymus.
AB  - During embryogenesis, colonization of the thymic rudiment by hemopoietic
      progenitor cells depends on the adhesion of these cells to the jugular
      endothelium. Previously, we showed that progenitor T cells (pro-T cells) interact
      with alpha 6 integrins present on vascular endothelium. Here, we demonstrate that
      anti-alpha 6 integrin antibodies reduced the number of thymocytes up to 80% in a
      congenic mouse model for thymus colonization by pro-T cells. In organotypic
      thymus cultures, the anti-alpha 6 integrin antibodies did not influence T cell
      development and proliferation. From this, we conclude that alpha 6 integrin
      participates in thymus homing. During mouse thymus ontogeny, alpha 6 integrin
      mRNA and protein expression was found as early as day 10 of development; at day
      11, perithymic endothelial cells were alpha 6 integrin positive. Two alpha 6
      integrin mRNA exist which are produced by alternative exon usage. The longer
      form, alpha 6 integrin, predominates during early embryonic stages, while the
      shorter alpha 6A form was present later during development. Although alpha 6
      integrins can be displayed by immature thymocytes, strongest expression was found
      on intra- and perithymic vascular endothelium. These data suggest that alpha 6
      integrins are involved in the homing of pro-T cells to the developing thymus by
      mediating adhesion of pro-T cells to the vascular endothelium.

PMID- 7621878
TI  - Cell cycle regulation of immunoglobulin class switch recombination and germ-line
      transcription: potential role of Ets family members.
AB  - Previous studies have indicated that transcription of germ-line (GL) CH genes is
      necessary to obtain immunoglobulin (Ig) class switching. We report here a
      correlation between proliferation, switching and GL transcripts. Smu-S gamma 1
      switch recombination in lipopolysaccharide (LPS) + interleukin-4 (IL-4)-activated
      mouse B cells was assayed by a digestion-circularization polymerase chain
      reaction. Switching to gamma 1 is reduced upon inhibition of DNA synthesis with
      hydroxy-urea (HU) or aphidicholin (AC). Incubation of activated B cells with HU
      severely reduces steady-state levels of GL gamma 1 and epsilon RNA. By utilizing
      elutriation to synchronize B cell blasts in different phases of the cell cycle,
      it was found that GL gamma 1 transcripts are mainly expressed in G1 and S phases,
      but not in G0. Using the electrophoretic mobility shift assay, we characterized
      two major LPS-induced complexes, which bind to the GL gamma 1 promoter and are
      expressed at levels which correlate with the amount of LPS-induced DNA synthesis.
      Furthermore, the intensity of the complexes is reduced when cells are arrested
      with the DNA synthesis inhibitors HU or AC. Elutriation experiments revealed that
      the complexes are expressed in G1 and S, but not in G0. They bind to an Ets
      consensus element near the major initiation sites used in proliferating cells.
      The possible implications of these findings for Ig isotype switching are
      discussed.

PMID- 7621879
TI  - Human V gamma 9-V delta 2 cells are stimulated in a cross-reactive fashion by a
      variety of phosphorylated metabolites.
AB  - Many different pathogens stimulate cells bearing the V gamma 9-V delta 2 T cell
      receptor (TCR), which represent the most abundant population of human gamma delta
      cells. The antigens responsible for the stimulation of these gamma delta cells
      are not well characterized. Here, we describe six non-peptidic molecules which
      share this property: isopentenylpyrophosphate, dimethylallylpyrophosphate, 2,3
      diphosphoglyceric acid, glycerol-3-phosphoric acid, xylose-1-phosphate, and
      ribose-1-phosphate. All these molecules are naturally occurring metabolites in
      prokaryotic and eukaryotic cells, and stimulate freshly isolated gamma delta
      cells from peripheral blood of different donors as well as established gamma
      delta clones. Comparison of their structure with that of similar but inactive
      molecules showed that both the number and position of the phosphate groups, as
      well as the residues connected with the carbon backbone are required for
      stimulation. The CD3-TCR complex is involved in cell triggering as shown by
      inhibition with anti-CD3 Fab fragments. However, all gamma delta clones were
      broadly cross-reactive and we could not isolate cells specific for only one
      ligand. The capacity of this frequent subset of gamma delta cells to recognize
      common bacterial metabolites confers the advantage to react rapidly to different
      invading pathogens.

PMID- 7621880
TI  - Functional analysis of avian class I (BFIV) glycoproteins by epitope tagging and
      mutagenesis in vitro.
AB  - Similarities between the physical structures of avian and mammalian major
      histocompatibility complex (MHC) class I glycoproteins have been proposed based
      on comparative alignment of their amino acid sequences. To investigate the
      physical structure of the chicken class I glycoprotein, we cloned the cDNA
      representing the BFIV locus of the B21 haplotype. A unique, chimeric class I
      glycoprotein was constructed by incorporating an epitope tag (FLAG) at the N
      terminus. Monoclonal antibodies to the FLAG epitope served to monitor cell
      surface expression for functional analysis of the BFIV21 class I glycoprotein.
      The chimeric class I glycoprotein was expressed in target cells using an avian
      leukosis virus (ALV)-derived retrovirus vector (RCASBP). The presence of the FLAG
      epitope did not interfere with either alloantibody recognition or cytotoxic T
      lymphocyte interaction. Functional analysis employing site-directed mutagenesis
      identified BF amino acid residues forming serologic epitopes as well as residues
      important in antigen presentation to ALV-induced cytotoxic T lymphocytes. BF
      residues 78 and 81, corresponding to HLA 79 and 82, form an antibody epitope with
      a slight effect on ALV antigen presentation, consistent with their predicted
      orientation based on the HLA-A2 crystal structure. Alignment of the BFIV21
      sequence with previously published BFIV sequences revealed polymorphisms at
      position 34 (HLA 34), a monomorphic residues in HLA and H-2. Residue 34 is
      located in pocket B and is predicted to contact the main-chain carbon of peptides
      bound in HLA-A2. A site-directed substitution in BFIV residue 34 dramatically
      alters ALV antigen presentation by the BFIV21 class I glycoprotein. These data
      indicate that the physical molecular structure of the chicken MHC class I
      glycoprotein is similar to HLA.

PMID- 7621881
TI  - Recombinant CD30 ligand and CD40 ligand share common biological activities on
      Hodgkin and Reed-Sternberg cells.
AB  - The CD30 ligand (CD30L) and CD40L are members of the tumor necrosis factor (TNF)
      protein superfamily, CD30L and CD40L are mainly expressed as membrane-bound
      proteins by activated T cells. CD30L and CD40L are costimulatory for T cell
      proliferation and activation. Further, CD40L is a critical signal for T cell
      dependent activation of B cells. Primary and cultured Hodgkin and Reed-Sternberg
      (H-RS) cells, the neoplastic component of Hodgkin's disease (HD), express high
      levels of the counterreceptors CD30 and CD40. We have found that both the
      recombinant CD30L and CD40L enhanced interleukin (IL)-6, TNF and lymphotoxin (LT)
      alpha release from cultured H-RS cells. In addition, CD40L, but not CD30L,
      induced IL-8 secretion. CD30L and CD40L seem to share some redundant biological
      activities involved in the deregulated secretion of cytokines known to play a
      central role in the clinical presentation and pathology of HD. Further, CD30L
      enhanced surface expression of intercellular adhesion molecule-1 (ICAM-1/CD54) on
      cultured H-RS cells, which is frequently overexpressed on primary H-RS cells.
      CD30L- and CD40L-enhanced CD54 surface expression is followed by elevated
      shedding of CD54, as shown by detection of elevated 82-kDa soluble (s) CD54
      levels in culture supernatants after stimulation with both ligands. CD30L and
      CD40L share common pleiotropic biological activities on CD30+/CD40+ H-RS cells
      and are elements of the cytokine and cell contact-dependent activation network
      typical for HD, a tumor of cytokine producing cells.

PMID- 7621882
TI  - Association of the transmembrane 4 superfamily molecule CD53 with a tyrosine
      phosphatase activity.
AB  - Cell surface proteins of the transmembrane 4 superfamily (TM4SF) are a newly
      characterized family of proteins which are presumed to span the plasma membrane
      four times. The function of this family of molecules is poorly understood, but
      based on monoclonal antibody studies there is some evidence that they may be
      involved in transmembrane signal transduction and regulation of cell
      proliferation, differentiation, or both, in a number of different cell types.
      CD53 is a member of this family that is expressed on leukocytes, and transduces
      activation signals through unknown mechanisms that may involve phosphorylation
      events. However, CD53 has never been shown to associate directly with kinases.
      Here, we show by immunoprecipitation from cell lysates of lymph nodes and a
      thymoma cell line, that immune complexes of rat CD53 contain tyrosine phosphatase
      activity. The CD53-associated phosphatase was able to dephosphorylate in vitro
      the phosphorylated tyrosine kinase Lck, as well as a synthetic substrate, and its
      activity was abrogated by a tyrosine phosphatase inhibitor. Although its identity
      has not been established, it is clear from depletion experiments that it is not
      CD45. CD63, a second member of the TM4SF, also co-precipitates a phosphatase
      activity from rat basophilic leukemia cells. These results demonstrate that the
      TM4SF members associate with tyrosine phosphatases. It seems possible that such
      associated phosphatases may contribute to the signal transduction capacity of
      TM4SF molecules.

PMID- 7621883
TI  - Analysis of interleukin receptor gene expression in mouse fetal liver by
      quantitative polymerase chain reaction.
AB  - We describe a simplified and sensitive polymerase chain reaction (PCR)-based
      method for the quantification of low-abundance RNA for mouse cytokine receptor
      genes. Accurate quantification is achieved in a two-step protocol which uses a
      synthetic RNA as an internal standard. The proper titration of the amount of mRNA
      molecules is followed by a kinetic analysis which ensures precise measurement.
      This quantitative PCR method provides a rapid and reliable way to quantify the
      amount of cytokine receptor mRNA in samples containing as few as 1000 molecules
      of RNA for a cytokine receptor target gene. We illustrate our approach by
      quantifying mRNA levels for two families of cytokine receptor genes in the fetal
      liver and bone marrow of the mouse. Our results reveal early and abundant
      expression of the genes encoding the signal transducing subunits interleukin-2
      receptor gamma and gp130. Their expression seems to precede that of the genes
      encoding the specific subunits of these interleukin receptor systems.

PMID- 7621884
TI  - A point mutation in the human CD45 gene associated with defective splicing of
      exon A.
AB  - CD45 is a receptor-type protein tyrosine phosphatase involved in the regulation
      of lymphocyte activation. Different CD45 isoforms are generated by alternative
      splicing of three variable exons (A, B and C). The pattern of CD45 splicing
      depends upon cell type and state of activation. CD45RA isoforms (containing exon
      A-encoded sequences) can usually be found on a subset of resting T cells, but not
      on activated T cells. We have recently described a variant pattern of CD45RA
      expression which is characterized by continuous expression of CD45RA molecules on
      activated and memory T cells. Here, we demonstrate that this phenotype is
      associated with heterozygosity for a point mutation at nucleotide position 77 of
      exon A, leading to a C-->G transition. This mutation does not change the protein
      sequence of the CD45RA isoform. We conclude that position 77 is part of a motif
      necessary for splicing of exon A, which supports the hypothesis that sequences
      within exons have significant effects on alternative splicing. The mutation of
      this motif might prevent binding of a transacting splice factor. In the
      heterozygous state, this mutation is not associated with impaired T cell
      reactivity. Functional consequences of the homozygous state remain to be
      elucidated.

PMID- 7621885
TI  - Differential contribution of the FcR gamma chain to the surface expression of the
      T cell receptor among T cells localized in epithelia: analysis of FcR gamma
      deficient mice.
AB  - The function of the Fc receptors gamma chain (FcR gamma) for the expression of
      the T cell receptor (TCR) complex and for T cell development, especially for T
      cells localized in epithelia, was investigated by analyzing FcR gamma-deficient
      mice. In wild-type mice, CD8 alpha alpha + beta -TCR alpha beta + T cells of
      intestinal intraepithelial lymphocytes (i-IEL) utilized CD3 zeta homodimers and
      zeta-FcR gamma heterodimers, whereas CD8 alpha alpha + beta -TCR gamma delta + i
      IEL used zeta-FcR gamma and FcR gamma homodimers in the TCR complex. On the other
      hand, these T cells in FcR gamma-deficient mice contained only zeta homodimers.
      The surface expression of the TCR complex was reduced in CD8 alpha alpha + beta 
      i-IEL and dendritic epidermal T cells (DETC) in these mice, whereas the
      development of these T cells was normal. The degree of reduction appeared to
      depend on the expression level of FcR gamma. In contrast to these populations,
      TCR gamma delta + intraepithelial T cells in reproductive organs (r-IEL) were
      dramatically decreased, suggesting that the development of r-IEL is FcR gamma
      dependent, probably due to the predominant usage of FcR gamma homodimers in the
      TCR complex. These results indicate that the FcR gamma chain contributes
      differently to the TCR expression and to the development of T cells localized in
      epithelia.

PMID- 7621886
TI  - T cell repertoire and clonal deletion of Mtv superantigen-reactive T cells in
      mice lacking CD4 and CD8 molecules.
AB  - CD4-CD8- double-negative T cells constitute a lymphocyte subpopulation within the
      thymus and peripheral lymphatic organs that express a unique T cell receptor
      (TCR) repertoire and do not undergo negative selection. To test whether these
      cells develop as a distinct lineage or due to altered selection in the absence of
      CD4 and CD8 expression, we analyzed the TCR repertoire in mice lacking both CD4
      and CD8 accessory molecules after homologous recombination (CD40/0CD80/0). We
      show that mature T cells of CD40/0CD80/0 mice express an unbiased diverse TCR V
      beta repertoire comparable to wild type mice. In addition, clonal deletion of
      mouse mammary tumor virus superantigen-reactive T cells did occur in CD40/0CD80/0
      mice. These data show that the intrinsic lack of CD4 and CD8 expression has no
      effect on the mature TCR repertoire and that clonal deletion of superantigen
      reactive cells is independent of CD4 and CD8 co-receptors.

PMID- 7621887
TI  - Differences in processing of an autoantigen by DR4:Dw4.2 and DR4:Dw14.2 antigen
      presenting cells.
AB  - Variations in antigen processing can influence class II-restricted T cell
      responses. We now report a highly significant difference (p < 0.001) between the
      ability of antigen-presenting cells from three HLA-DR4:Dw14.2 (Arg71) and six
      DR4:Dw4.2 (Lys71) individuals to present recombinant or native acetylcholine
      receptor antigens to a myasthenia gravis T cell clone. The difference was
      greatest with longer antigens, and not seen with short synthetic peptides,
      suggesting that it may result from a difference in antigen processing between the
      two alleles. The results were not related to the presence of myasthenia gravis or
      of steroid therapy. They could, however, be of relevance in rheumatoid arthritis
      where particularly severe disease associates with Dw4.2/Dw14.2 heterozygosity.

PMID- 7621888
TI  - IgA production by peritoneal cavity B cells is IL-6 independent: implications for
      intestinal IgA responses.
AB  - We have shown previously both in vitro and in vivo that IL-6 is an important
      factor for the development of IgA-producing B cells. However, despite the lack of
      this cytokine in mice with targeted disruption of the interleukin (IL)-6 gene
      (gene knockout mice), a substantial number of IgA-producing plasma cells occur in
      their intestinal mucosa. The experiments reported here indicate that there is a
      population of IgA-producing B cell precursors originating from the peritoneal
      cavity, distinguished from conventional Peyer's patch-derived precursors by their
      expression of CD5, and that IgA secretion by these cells is IL-6-independent.
      Further, there is an increase in CD5 expression among brightly staining IgA
      producing cells obtained from the intestinal lamina propria of IL-6 gene
      disrupted mice compared to normal controls. These data suggest an explanation for
      the persistence of IgA-producing plasma cells in the intestinal mucosa of IL-6
      depleted mice and indicate the importance of IL-6 for development of conventional
      precursors of IgA-producing B cells, but not those derived from the peritoneal
      cavity pool.

PMID- 7621889
TI  - Endothelin-1 does not phosphorylate phospholamban and troponin I in intact
      beating rat hearts.
AB  - To determine a role of phosphorylation of specific cardiac regulatory proteins in
      the positive inotropic effect of endothelin-1, we examined phosphorylation of
      sarcoplasmic reticulum and myofibrillar proteins in perfused beating rat hearts
      treated with endothelin-1. In parallel experiments, the effects of isoprenaline
      and phorbol-12,13-dibutyrate (PDB) on protein phosphorylation were also tested.
      In 32Pi-labeled hearts, perfusion with isoprenaline (100 nM) caused 4.4- and 10.4
      fold increases in the degree of phosphorylation of phospholamban in sarcoplasmic
      reticulum and of troponin I in myofibrils, respectively. In contrast, neither
      endothelin-1 (100 nM) nor PDB (1 microM) significantly changed the
      phosphorylation state of these proteins. These findings provide evidence that
      phosphorylation of major cardiac regulatory proteins is not responsible for the
      positive inotropic action of endothelin-1.

PMID- 7621890
TI  - Proton inhibition of [3H]resiniferatoxin binding to vanilloid (capsaicin)
      receptors in rat spinal cord.
AB  - Protons and capsaicin activate overlapping subsets of sensory nerves by opening
      ion conductances of similar properties. We have used the [3H]resiniferatoxin
      binding assay utilizing rat spinal cord membranes to elucidate the possible
      interaction of protons at the vanilloid (capsaicin) receptor. Using low pH (pH
      6.0 and pH 5.0) buffers, a time-dependent gradual decrease was observed in
      specific resiniferatoxin binding. Protons inhibited resiniferatoxin binding with
      an IC50 of pH 5.3 +/- 0.1. In experiments in which the concentration of
      [3H]resiniferatoxin was varied, protons reduced the Bmax value by approximately
      40% with a corresponding 2-fold decrease in affinity. No change however, was
      observed in binding cooperativity (the Hill coefficients were 1.7 +/- 0.1 and 1.6
      +/- 0.2 in the presence of pH 7.4 and pH 5.0 buffers, respectively). These
      changes in binding parameters are consistent with a non-competitive or,
      alternatively, mixed inhibitory mechanism. The remaining resiniferatoxin binding
      sites bound capsaicin with an affinity (Ki = 5.0 +/- 1.0 microM) very similar to
      that determined in the presence of a pH 7.4 buffer (Ki = 3.0 +/- 1.5 microM). A
      cyclooxygenase inhibitor, indomethacin (up to 10 microM), did not prevent the
      action of protons on resiniferatoxin binding; neither was it mimicked by
      prostanoids (prostaglandin I2 and E1, both at 100 microM). We conclude that
      protons interact at vanilloid receptors in the rat spinal cord; this interaction
      is either non-competitive or mixed in nature, and probably is not related to
      prostanoid generation. Protons and/or putative proton-generated mediators might
      represent endogenous modulators of the vanilloid receptor.

PMID- 7621891
TI  - Isradipine affects histamine-induced cytosolic Ca2+ movements in human
      endothelial cells.
AB  - Although endothelial actions of dihydropyridines remain controversial, isradipine
      has been observed to exert anti-atherosclerotic actions in which endothelium
      could be involved. This study was designed to investigate the direct effects of
      isradipine on cytosolic Ca2+ concentration in cultured human umbilical vein
      endothelial cells. Isradipine (from 10 nM to 1 microM) had no effect on
      unstimulated cells but dose-dependently decreased both the transient [Ca2+]i peak
      and the sustained increase induced by histamine. Its maximal effects were reached
      at 0.1 microM. In the absence of Ca2+ influx or in depolarized cells, 1 microM
      isradipine still significantly decreased the transient [Ca2+]i peak (by 23 +/- 8%
      and 42 +/- 11%). Ca2+ influx induced by re-establishment of transmembrane Ca2+
      gradient was also inhibited by isradipine, as was that induced by 1 microM
      thapsigargin. These results demonstrate that isradipine is able to reduce both
      Ca2+ release from internal stores and the consequent Ca2+ entry in stimulated
      human endothelial cells.

PMID- 7621892
TI  - Coupling of the endothelin ETA and ETB receptors to Ca2+ mobilization and Ca2+
      sensitization in vascular smooth muscle.
AB  - Effects of endothelins on cytosolic Ca2+ level ([Ca2+]i) and contraction were
      examined in the swine pulmonary artery and vein. In the artery, endothelin-1 and
      endothelin-3, but not sarafotoxin S6c and IRL 1620 (300 nM each), induced
      transient increase followed by sustained increase in [Ca2+]i and sustained
      contraction. These effects were inhibited by the ETA receptor antagonist, BQ-123.
      In the vein, endothelin-1 and endothelin-3 (300 nM each) induced sustained
      increase in [Ca2+]i and sustained contraction whereas sarafotoxin S6c and IRL
      1620 (300 nM each) transiently increased both [Ca2+]i and contractile tension.
      The ETB receptor in the vein was desensitized by pretreatment with sarafotoxin
      S6c, abolishing the effects of sarafotoxin S6c and IRL 1620 without changing the
      effects of endothelin-1 and endothelin-3. In contrast, an ETB antagonist, RES-701
      1, antagonized the effects of IRL 1620 without changing the effects of other
      stimulants. In both artery and vein, the maximum contraction induced by these
      stimulants was greater than that induced by KCl at a given [Ca2+]i. In the
      absence of external Ca2+, endothelin-1 and endothelin-3 induced transient
      increase in [Ca2+]i and slow sustained contraction in both artery and vein. In
      the vein, sarafotoxin S6c induced small sustained contraction without changing
      [Ca2+]i. In the permeabilized artery and vein, endothelin-1 augmented the
      contraction induced by Ca2+. These results suggest that the ETA receptors in the
      artery and vein are coupled to Ca2+ release (which does not seem to trigger
      contraction), Ca2+ influx and Ca2+ sensitization.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7621893
TI  - Triiodo-L-thyronine enhances TRH-induced TSH release from perifused rat
      pituitaries and intracellular Ca2+ levels from dispersed pituitary cells.
AB  - There is now increasing evidence that Ca2+ serves as the first messenger for the
      prompt and non-genomic effects of 3,5,3' triiodo-L-thyronine (T3) in several
      tissues. We have previously shown that the first phase of thyroid stimulating
      hormone (TSH) release in response to thyrotropin-releasing hormone (TRH) can be
      potentiated by messengers of hypothalamic origin, by a Ca(2+)-dependent
      phenomenon involving the activation of dihydropyridine-sensitive Ca2+ channels.
      By perifusing rat pituitary fragments, we have investigated whether T3 would
      modify TSH release when the hormone is applied for a short time (i.e. 30 min)
      before a 6 min pulse of physiological concentration of TRH, thus excluding the
      genomic effect of T3. We show that: (1) increasing concentrations of T3 (100 nM
      10 microM) in the perifused medium potentiates the TRH-induced TSH release in a
      dose-dependent manner; (2) the T3 potentiation is not reproduced by
      diiodothyronine and T3 does not potentiate the increase if TSH release induced by
      a depolarizing concentration of KCl; (3) the protein synthesis inhibitor
      cycloheximide, does not significantly modify the effect of T3; (4) addition of
      Co2+, nifedipine, verapamil, or omega-conotoxin in the medium, at a concentration
      which does not modify the TSH response to TRH, reverses the T3 potentiation of
      that response. We also tested whether T3 would change intracellular
      concentrations of Ca2+, by measuring [Ca2+]i with fura-2 imaging on primary
      cultures of dispersed pituitary cells, either in basal conditions or after
      stimulation by TRH or/and T3. Both substances induced a fast increase of [Ca2+]i,
      with a peak at 15 s, followed by a subsequent progressive decay with TRH and a
      rapid return with T3. Our data suggest that T3 enhances TRH-induced TSH release
      by a protein synthesis-independent and Ca(2+)-dependent phenomenon, probably due
      to an increase in Ca2+ entry through the activation of dihydropyridine- and omega
      conotoxin-sensitive Ca2+ channels. They also show that T3 may acutely enhance
      [Ca2+]i in pituitary cells. These findings support the idea of the occurrence of
      a prompt and stimulatory role of T3 at the plasma membrane level in normal rat
      pituitary gland.

PMID- 7621894
TI  - Anti-tumour effect of aromatase inhibitor, CGS16949A, on human breast cancer
      cells.
AB  - The growth inhibitory effect of a new non-steroidal aromatase inhibitor,
      CGS16949A (Fadrozole hydrochloride: [4-(5,6,7,8-tetrahydro-imidazo-[1,5a]-pyridin
      5-yl) benzonitrile monohydro chloride]) was studied in human breast cancer cells
      MCF-7 and T47D. The aromatase activity of MCF-7 was inhibited by CGS16949A in a
      dose-dependent manner (IC50: 2.8 x 10(-9) M). The cells were incubated for 120 h
      in phenol red free RPMI 1640 containing 5% stripped foetal calf serum, 10(-8) M
      testosterone and various concentrations of CGS16949A. Testosterone-induced MCF-7
      growth was inhibited by CGS16949A almost completely at the concentrations as low
      as 10(-9) M, but was not inhibited by antiandrogenic cyproterone acetate (6
      chloro-1 beta,2 beta-dihydro-17-hydroxy-3'-H- cyclopropa[1,2]-pregna-1,4,6-triene
      3,20-dione acetate: CPA). On the other hand, the growth of T47D stimulated by
      testosterone was not inhibited by CGS16949A, but was inhibited by CPA. These data
      suggested that the aromatization of androgens should participate in the growth of
      MCF-7 and that one of the growth inhibitory mechanisms of CGS16949A should be the
      inhibition of the intracellular aromatase activity.

PMID- 7621895
TI  - Distribution of beta 3-adrenoceptor mRNA in human tissues.
AB  - The beta 3-adrenoceptor is a G protein-coupled receptor which mediates metabolic
      functions of the endogenous catecholamines epinephrine and norepinephrine.
      Questions exist regarding distribution of the beta 3-adrenoceptor in human
      tissue. In order to examine the distribution of beta 3-adrenoceptor mRNA in human
      tissues, we used sensitive and specific RNase protection assays without previous
      PCR amplification in an extensive list of human tissues. We confirm the presence
      of beta 3-adrenoceptor mRNA in human white fat from several locations, gall
      bladder, and small intestine, as well as extend the distribution of beta 3
      adrenoceptor mRNA to previously uncharacterized human tissues such as stomach and
      prostate. The presence of beta 3-adrenoceptor mRNA in human white adipose tissue
      has important implications regarding possible use of beta 3-adrenoceptor
      selective agonists as anti-obesity agents, and the demonstration of beta 3
      adrenoceptor mRNA in a number of gastrointestinal tissues and prostate raises the
      question of the role of the beta 3-adrenoceptor in motility and secretory
      processes.

PMID- 7621896
TI  - Felbamate, a novel antiepileptic drug, reverses N-methyl-D-aspartate/glycine
      stimulated increases in intracellular Ca2+ concentration.
AB  - Felbamate, 2-phenyl-1,3-propanediol dicarbamate, is a novel, orally active
      anticonvulsant that has recently been approved for the treatment of Lennox
      Gastaut syndrome and partial onset seizures in the United States. Felbamate is
      active in a broad range of animal anticonvulsant tests. Although its mechanism of
      action has yet to be fully elucidated, felbamate appears to act by inhibiting the
      spread of seizures and elevating seizure threshold. One proposed mechanism of
      action for felbamate is via the NMDA receptor complex. Previous studies have
      demonstrated the ability of felbamate to inhibit glycine binding at the NMDA
      receptor complex. The present study examined the effects of felbamate on
      NMDA/glycine-stimulated increases in intracellular calcium (Ca2+) using cultured
      rat hippocampal neurons. The results of these experiments demonstrate that
      felbamate inhibits NMDA/glycine-stimulated increases in intracellular Ca2+ with a
      minimal effective concentration of 100 microM.

PMID- 7621897
TI  - Desensitization of beta-adrenergic responses in adipocytes involves receptor
      subtypes and cAMP phosphodiesterase.
AB  - Acute exposure of isolated adipocytes to isoproterenol induces the
      desensitization of lipolytic responses to norepinephrine and selective beta 1-,
      beta 2- and beta 3-adrenoceptor agonists, as well as the adrenocorticotropic
      hormone 1-24 fragment (ACTH). Forskolin and 8-bromo-cAMP responses are also
      desensitized. When lipolysis was measured in the presence of OPC 3911 [N
      cyclohexyl-N-2-hydroxyethyl-4(6-(1,2-dihydro-2- oxoquinolyloxy))butyramide], a
      specific inhibitor of the cAMP phosphodiesterase of adipocytes, the
      desensitization of all lipolytic agents--except the beta 2-adrenoceptor agonist-
      was abolished. Isoproterenol induced a similar loss (35%) of both membrane beta 1
      and beta 2-adrenoceptors and an uncoupling of beta 1-adrenoceptors, but did not
      modify the weak coupling of control beta 2-adrenoceptors. These data suggest that
      isoproterenol induced (i) an activation of the cAMP phosphodiesterase, which is
      solely responsible for the desensitization of norepinephrine response as well as
      beta 1- and beta 3-adrenoceptor mediated responses and (ii) an additional
      desensitization of the sole beta 2-adrenergic signaling system which suggests a
      subtype-selective pattern of regulating processes.

PMID- 7621898
TI  - Modulation of recombinant alpha 6 beta 2 gamma 2 GABAA receptors by neuroactive
      steroids.
AB  - The sensitivity of the recombinant alpha 6 beta 2 gamma 2 GABAA receptor
      expressed in HEK 293 cells to neuroactive steroids was studied. The steroids 3
      alpha-hydroxy-5 alpha-pregnan-20-one (3 alpha-OH-DHP), pregnenolone sulfate and 3
      alpha-OH-DHP sulfate have different modulatory effects on [3H]muscimol or
      [3H]Ro15-4513 binding to the alpha 6 beta 2 gamma 2 than to the alpha 1 beta 2
      gamma 2 receptor. Binding of both radioactive ligands to the alpha 6 beta 2 gamma
      2 receptor was maximally potentiated with each steroid used (10 nM) and decreased
      with further increases in steroid concentration. Using whole-cell recording, the
      GABA response of clusters of transfected HEK 293 cells was strongly potentiated
      by 3 or 10 nM 3 alpha-OH-DHP. In contrast, this response was reduced by 100 nM 3
      alpha-OH-DHP. This latter effect appears to be related to the acceleration of the
      GABA response desensitization, observed in isolated cells. 3 alpha-OH-DHP (10 or
      100 nM) was able to activate a response in the absence of GABA. It is proposed
      that the interaction of neuroactive steroids with the alpha 6 beta 2 gamma 2
      receptor involves at least two distinct binding sites. One of them might be
      located close to the GABA binding site.

PMID- 7621899
TI  - Inhibition by nitrendipine of 86Rb+ fluxes in subconfluent MDCK cells.
AB  - Part of the natriuretic mechanism of dihydropyridine Ca2+ channel antagonists
      involves the inhibition of renal tubular sodium reabsorption. To identify the
      membrane ion transport system involved in this natriuretic action, we tested
      nitrendipine on unidirectional 86Rb+ fluxes in Madin-Darby canine kidney (MDCK)
      cells. To dissect between direct and indirect effects (via cytosolic Ca2+) of
      nitrendipine, the compound was re-examined on ion fluxes in human erythrocytes.
      In MDCK cells, external Ca2+ (3 mM), adrenalin (100 microM) and the Ca2+
      ionophore A23187 (20 microM) strongly and transiently stimulated 86Rb+ efflux.
      All these stimulatory actions were fully inhibited by quinine (1 mM) suggesting
      that they reflect the opening of Ca(2+)-sensitive K+ channels. Nitrendipine was
      able to inhibit these Ca(2+)-sensitive K+ channels, bit this inhibitory action
      required concentrations of the compound (approximately 100 microM). Regarding
      86Rb+ influx, the most significant result with nitrendipine was a partial
      inhibition of bumetanide-sensitive 86Rb+ influx. This effect represented a
      maximal flux inhibition of about 70% and required very low nitrendipine
      concentrations (IC50 approximately 1 nM). The Ca2+ ionophore A 23187 strongly
      stimulated bumetanide-sensitive 86Rb+ influx in MDCK cells. Conversely, a very
      important reduction (approximately 79%) of this influx component was found in
      Ca2+ depleted cells. In human red blood cells, Na+, K+, Cl- cotransport fluxes
      were resistant to nitrendipine, even at high concentrations of the compound (100
      500 microM). Conversely, Ca(2+)-sensitive K+ channels were inhibited by
      nitrendipine with IC50 = 6 +/- 3 microM (mean +/- S.E.M., n = 3).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7621900
TI  - Kinetic studies on the interaction of nonlabeled antagonists with the angiotensin
      II receptor.
AB  - Angiotensin AT1 receptor antagonists are divided into two types, surmountable and
      insurmountable, based on the way they inhibit angiotensin II-induced
      vasoconstriction. To elucidate what causes the difference, we studied how
      antagonists associate with and dissociate from AT1 receptor sites in rat liver
      membranes. Three antagonists, 6-propyl-7-oxo-4[[2'-(1H-tetrazol-5-yl)biphenyl-4
      yl]methyl]-4,7- dihydropyrazolo[1,5-a]pyrimidine-3-carboxylic acid (SRL1080227),
      2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H- benzimidazole-7
      carboxylic acid (CV-11974) and 2-butyl-3-[[2'-(1H-tetrazol-5-yl)biphenyl-4
      yl]methyl]-3H-imidazo- [4,5-b]pyridine (FK739), showed competitive antagonism
      when they were added simultaneously with [125I]angiotensin II, but CV11974 and
      SRL1080227 showed apparently noncompetitive antagonism when membranes were
      preincubated with each antagonist. The longer the preincubation time with CV11974
      or SRL1080227 was, the more effectively the antagonist inhibited
      [125I]angiotensin II binding, while the inhibition by FK739 did not change with
      the preincubation time. To estimate their dissociation rate from the receptor
      binding site, we studied [125I]angiotensin II binding to membranes which had been
      preincubated with each antagonist and washed twice. Membranes pretreated with
      FK739 completely recovered the ability to bind [125I]angiotensin II with a period
      of 60 min, while membranes preincubated with CV11974 did not read this level of
      recovery. [125I]angiotensin II binding to membranes preincubated with SRL1080227
      increased gradually, but did not reach the control level during the experiment.
      The kinetic properties of SRL1080227, CV11974 and FK739 were consistent with
      their characteristic modes in inhibiting angiotensin II-induced contraction of
      isolated rabbit aorta and decreasing blood pressure of spontaneously hypertensive
      rats.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7621901
TI  - Beta-adrenoceptor agonists interfere with glucocorticoid receptor DNA binding in
      rat lung.
AB  - Inhaled beta 2-adrenoceptor agonists are the most effective bronchodilator
      treatment in asthma, yet paradoxically high doses may be associated with
      increased asthma morbidity and mortality. Steroids are the most effective therapy
      in controlling asthmatic inflammation and act by binding to specific sequences of
      DNA (GRE), thus modulating gene transcription. We report that in rat lung, the
      beta 2-adrenoceptor agonists, salbutamol and fenoterol, decrease the binding of
      glucocorticoid receptors to GRE, by 46 +/- 4% although it has no effect on the
      affinity or number of glucocorticoid receptors. The inhibition of GRE binding by
      salbutamol is concentration-dependent, can be blocked by propranolol and is seen
      following forskolin treatment. This effect appears to be due to an interaction
      between the glucocorticoid receptor and the transcription factor, cAMP response
      element binding protein (CREB), which is activated by high concentrations of beta
      2-adrenoceptor agonists. We suggest that by this mechanism high doses of inhaled
      beta 2-adrenoceptor agonists may inhibit the anti-inflammatory effects of
      endogenous glucocorticoids and exogenous corticosteroids used for asthma therapy.

PMID- 7621902
TI  - Effect of ageing and propranolol administration on myocardial beta-adrenoceptor
      receptor function in mature rats.
AB  - Ageing is accompanied by diminishing myocardial tissue beta-adrenoceptor
      responses. The relative contribution of maturation and senescence to reported age
      related changes in cell-surface beta-adrenoceptor dysfunction has not been
      established, since previous investigation has incorporated young rats lacking
      full maturity. We have examined myocardial ventricle membrane beta-adrenoceptor
      function in mature young (6 month) and old (26 month) male Wistar rats and the
      effect of propranolol infusion for seven days on beta-adrenoceptor function in
      these groups. beta 1-adrenoceptors comprised 63-72% of total beta-adrenoceptor
      density in both groups. beta 1-adrenoceptor densities were similar in young and
      old rats (young, 20.4 +/- 2.3; old, 24.7 +/- 1.4 fmol/mg protein +/- S.E.). beta
      2-adrenoceptor densities were higher in older rats (young, 8.2 +/- 0.5, n = 9;
      old, 13.6 +/- 1.8, n = 9 fmol/mg protein +/- S.E., P < 0.025). Subcutaneous
      infusion of propranolol for seven days with miniosmotic pumps was accompanied by
      an increase in beta 1- and beta 2-adrenoceptor densities in young rats only (beta
      1-, 38%, P < 0.05; beta 2- 52%, P < 0.025). beta 1-adrenoceptor agonist affinity
      and adenylate cyclase response to isoprenaline, GTP, Gpp(NH)p, Mn2+ and forskolin
      were not affected by age or propranolol infusion in either age-group. These
      findings demonstrate that male Wistar rats do not exhibit changes in myocardial
      ventricle beta-adrenoceptor-G-protein coupling capacity or adenylate cyclade
      activation with ageing beyond maturity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7621903
TI  - Involvement of non-muscarinic receptors in phosphoinositide signalling during
      soman-induced seizures.
AB  - Previous investigations have indicated that soman-induced convulsions involve the
      inositol lipid signalling system. We previously reported that 10 min after the
      onset of seizures, inositol 1,4,5-triphosphate (IP3) build-up was coupled to
      activation of non-muscarinic receptor subtypes. In the present study, we
      demonstrate that (1) in addition to muscarinic receptors, histamine H1 subtypes
      and glutamate metabotropic receptors contribute to the first IP3 increase (first
      10 min of seizures) and (2) the histamine H1 subtype and glutamate metabotropic
      receptors are also involved in the second step of inositol phosphate response
      (after 10 min of seizures). alpha 1-adrenoceptor and 5-HT2 receptors, known to be
      coupled to phosphoinositide turnover, did not participate in soman-induced IP3
      response. Neurochemical interactions between cholinergic, histamine H1 and
      glutamate metabotropic systems, responsible of the phosphoinositide hydrolysis
      under soman are envisaged.

PMID- 7621904
TI  - Inducible expression of alpha 1B-adrenoceptors in DDT1 MF-2 cells: comparison of
      receptor density and response.
AB  - Hamster DDT1 MF-2 smooth muscle cells natively express alpha 1B-adrenoceptors
      which are linked to phosphatidylinositol hydrolysis. We studied the relationship
      between alpha 1B-adrenoceptor density and response in this cell line by stable
      transfection with an isopropyl-beta-D-thiogalactoside (IPTG)-inducible vector
      (pOP alpha 1B) containing the hamster alpha 1B-adrenoceptor cDNA. Transfected
      cells showed a 2-fold increase in receptor density compared to untransfected
      cells due to constitutive activity of the uninduced vector. Induction of vector
      expression caused a time-dependent increase in receptor density, reaching a
      maximum 8-fold increase after 48 h. Exposure to different concentrations of
      inducing agent for 16 h caused a graded increase in both receptor density and
      norepinephrine-stimulated [3H]inositol phosphate (InsP) formation. A linear
      correlation between receptor density and maximum InsP response was observed.
      Induction of receptor expression did not alter the potency of norepinephrine in
      stimulating [3H]InsP formation, suggesting that there was no receptor reserve,
      even at very high expression levels. This inducible expression system should be
      useful for relating receptor density and responsiveness, and comparing the
      coupling efficiency of closely related subtypes in activating different signal
      transduction mechanisms.

PMID- 7621905
TI  - Positive allosteric interactions on cardiac muscarinic receptors: effects of
      chemical modifications of disulphide and carboxyl groups.
AB  - Changes in the allosteric effects of alcuronium on rat cardiac muscarinic
      receptors were investigated after chemical modifications of S-S bonds or free
      carboxyl groups. In membranes pretreated with dithiothreitol, alcuronium lost its
      positive action on the binding of [3H]methyl-N-scopolamine while its inhibitory
      effect on radioligand dissociation was preserved. In membranes pretreated with 1
      ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC), known to modify free carboxyl
      groups in proteins, the ability to bind [3H]methyl-N-scopolamine was preserved if
      the pretreatment had been performed in the presence of alcuronium, methyl-N
      scopolamine or carbachol, while the positive cooperative effect of alcuronium on
      [3H]methyl-N-scopolamine binding was only preserved in membranes that had been
      exposed to EDC in the presence of alcuronium. Methyl-N-scopolamine, carbachol and
      alcuronium differed in their ability to protect (against EDC) the action of
      alcuronium on the rate of [3H]methyl-N-scopolamine dissociation. The results
      suggest that the disulphide bridge connecting the first two extracellular loops
      of muscarinic receptors is important for the positive allosteric action of
      alcuronium and that three carboxyl groups (presumably aspartate residues) are
      involved in receptor interactions with alcuronium and methyl-N-scopolamine. The
      first group is important for the effect of alcuronium on the affinity for methyl
      N-scopolamine, the second is critical for the effect of alcuronium on the rate of
      methyl-N-scopolamine dissociation, and the third is critical for methyl-N
      scopolamine binding. Presumably, the two charged nitrogens of alcuronium
      associate with the first and the second of the three groups involved.

PMID- 7621906
TI  - Aminoglycoside antibiotics induce aggregation but not fusion of negatively
      charged liposomes.
AB  - The binding of aminoglycoside antibiotics to acidic phospholipids of membranes is
      an essential step in the development of both their renal and auditory toxicities,
      which could be associated with critical modifications of the membrane properties.
      This work examines the capacity of aminoglycosides to induce membrane aggregation
      and fusion. Three techniques were used in parallel: (i) measurement of the
      dequenching rate of a lipid-soluble fluorescent probe (octadecylrhodamine B)
      incorporated at self-quenched concentration in membranes; (ii) measurement of the
      increase in the energy transfer between two fluorescent derivatives of
      phospholipids; and (iii) electron microscopy of negatively-stained replicas. The
      results were compared with those obtained with spermine (an aggregating
      polycation) and melittin (a fusogenic peptide). The three approaches indicate
      that aminoglycosides induce liposomes aggregation, but not fusion. Aggregation is
      related to the capacity of each drug studied to bind phosphatidylinositol, as
      evaluated by its energy of interaction with this acidic phospholipid, and to its
      toxic potential. Membrane aggregation occurring in vivo could therefore
      contribute to, or be a determinant of this toxicity, which could rationally be
      screened for new derivatives by the methods applied here.

PMID- 7621907
TI  - Characterization of novel ligands for wild-type and natural mutant diazepam
      insensitive benzodiazepine receptors.
AB  - A series of benzodiazepine receptor ligands with different chemical structures
      were evaluated for their affinities at diazepam-sensitive and diazepam
      insensitive binding sites for [3H]Ro 15-4513 (ethyl-8-azido-5,6-dihydro-5-methyl
      6-oxo-4H-imidazo-[1,5a][1,4] benzodiazepine-3-carboxylate) in cerebellar GABAA
      receptors. Rats of Wistar strain and of alcohol-sensitive (ANT) and alcohol
      insensitive (AT) lines were used. The ANT rats possess a single point mutation in
      their GABAA receptor alpha 6 subunit, which makes their diazepam-insensitive
      sites sensitive to benzodiazepine agonists, unlike those of AT and Wistar rats.
      All compounds evaluated displayed high-affinity binding to diazepam-sensitive
      sites (Ki < 50 nM). In contrast, a wider range of affinities were observed at
      diazepam-insensitive sites which depended upon the basic structure and
      substitutions. The 7- and 8-halogen substituted imidazobenzodiazepines and 12
      halogen substituted diimidazoquinazolines displayed the highest affinities (Ki <
      15 nM), while intermediate to low affinities (100 < Ki < 4000 nM) were displayed
      by imidazoquinazolines, thienopyrimidines, one oxoimidazoquinoxaline, and some
      cyclopyrrolones. The imidazoquinoxalines evaluated displayed the lowest affinity
      (Ki > 10000 nM). The oxoimidazoquinoxaline, 6-chloro-3-(5-cyclopropyl-1,2,4
      oxadiazol-3-yl)-4,5-dihydro-5-isop ropyl-4-oxo-imidazo[1,5-a]quinoxaline (NNC 14
      0578) and suriclone represent the first benzodiazepine receptor full agonists to
      bind with relatively high affinity (Ki approximately 100 nM) to diazepam
      insensitive sites. The 5 position substituted methoxybenzyl, dimethylallyl, and 4
      fluorobenzyl oxoimidazoquinoxaline analogs demonstrated a 58-336-fold higher
      affinity for ANT than AT diazepam-insensitive sites.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7621909
TI  - Regulation of beta 1-adrenoceptors by glucocorticoids and thyroid hormones in
      fetal sheep.
AB  - The effects of betamethasone alone or in combination with thyroxine (T4) on ovine
      fetal beta-adrenoceptors were investigated at the molecular level. Ovine fetuses
      (126 days gestation; term = 150 days) were treated with a single ultrasound
      guided intramuscular injection of 0.5 mg/kg betamethasone, betamethasone + 50
      micrograms/kg T4, or saline. Forty-eight h after injection, lambs were delivered
      by cesarean section and evaluated three h for postnatal adaptation. Myocardial
      beta-adrenoceptor equilibrium dissociation constant (Kd) and maximal receptor
      density (Bmax), as assessed by [3H]dihydroalprenolol binding, were not
      significantly different in drug-treated groups compared to the control group.
      Northern hybridization and RNase protection assays of myocardial total RNA probed
      with a sheep beta 1-adrenoceptor riboprobe confirmed no changes in expression at
      the level of the gene. Levels of beta 1-adrenoceptor mRNA in the lung and brain
      were also unaffected by the treatments. Because other genes are responsive to
      glucocorticoids and thyroid hormones at this stage, the absence of up-regulation
      of beta-adrenoceptor number and steady-state levels of mRNA coding for beta 1
      adrenoceptor following fetal corticosteroid and thyroid hormone treatment may
      indicate a specific, developmentally regulated repressor mechanism.

PMID- 7621908
TI  - Coupling of muscarinic m1, m2 and m3 acetylcholine receptors, expressed in
      Chinese hamster ovary cells, to pertussis toxin-sensitive/insensitive guanine
      nucleotide-binding proteins.
AB  - Chinese hamster ovary (CHO) cells expressing recombinant human m1 (CHO-m1 cells),
      m2 (CHO-m2 cells), or m3 (CHO-m3 cells) muscarinic receptors were characterised
      pharmacologically with [3H]N-methylscopolamine. Agonist-stimulated coupling of
      these receptors with guanine nucleotide-binding proteins (G proteins) was
      measured by guanine nucleotide- and pertussis toxin-modification of carbachol
      competition-binding curves, and pertussis toxin-sensitivity of agonist-stimulated
      [35S]guanosine 5'-O-(3-thiotriphosphate) ([35S]GTP gamma S) binding, in membrane
      preparations of the CHO cell clones. High affinity agonist binding and agonist
      stimulated [35S]GTP gamma S binding was abolished in CHO-m2 cell membranes
      (expressing 99 +/- 25 fmol of [3H]N-methylscopolamine binding sites/mg protein)
      after pertussis toxin pretreatment of cells, suggesting that muscarinic m2
      receptors expressed in these cell membranes couple predominantly with pertussis
      toxin-sensitive G proteins. CHO-m1 (713 +/- 102 fmol/mg protein) and CHO-m3 (1212
      +/- 279 fmol/mg protein) cell membranes produced smaller elevations in agonist
      stimulated [35S]GTP gamma S binding considering the higher receptor levels,
      compared with CHO-m2 cell membranes. Pertussis toxin pretreatment of these clones
      also resulted in a significant attenuation of agonist-stimulated [35S]GTP gamma S
      binding suggesting that, under these experimental conditions, muscarinic m1 and
      m3 receptors can couple with both pertussis toxin-sensitive and pertussis toxin
      insensitive G proteins. Guanine nucleotide-modification of agonist binding in CHO
      m1 and CHO-m3 cell membranes was comparatively smaller than in CHO-m2 cell
      membranes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7621910
TI  - Exogenous histamine increases the somatostatin receptor/effector system in the
      rat frontoparietal cortex.
AB  - The present study examined the effects of histamine on somatostatin-like
      immunoreactivity levels, binding of 125I-[Tyr11]somatostatin to its specific
      receptors, somatostatin inhibition of basal and forskolin-stimulated adenylyl
      cyclase activity and inhibitory guanine-nucleotide binding protein (Gi) function
      in the rat frontoparietal cortex. An intracerebroventricular (i.c.v.) dose of 10
      micrograms or 1 microgram of histamine induced an increase in the number of
      specific 125I-[Tyr11]somatostatin receptors (590 +/- 22 vs 358 +/- 12 fmol/mg
      protein, P < 0.001 and 455 +/- 20 vs. 342 +/- 21 fmol/mg protein, P < 0.01,
      respectively) together with a decrease in their apparent affinity (0.76 +/- 0.04
      vs 0.39 +/- 0.02 nM, P < 0.001 and 0.60 +/- 0.03 vs 0.39 +/- 0.05 nM, P < 0.01,
      respectively) in rat frontoparietal cortex membranes. This increase in tracer
      binding was not due to a direct effect of histamine on the somatostatin receptors
      since no change in binding was produced when histamine was added directly to the
      incubation medium. No significant differences were seen for either the basal or
      forskolin-stimulated adenylyl cyclase activity in frontoparietal cortex membranes
      of histamine-treated rats as compared with the control group. In rats treated
      with 10 micrograms of histamine, however, somatostatin caused a significantly
      greater inhibition of basal and forskolin-stimulated adenylyl cyclase activity as
      compared to the control group (33 +/- 4% vs 19 +/- 1% inhibition, P < 0.05 and 31
      +/- 1% vs 21 +/- 3% inhibition, P < 0.05, respectively).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7621911
TI  - Competitive and allosteric binding of 2 alpha-DHET and its optical isomers to rat
      cardiac muscarinic receptors.
AB  - The possibility of both competitive and allosteric interactions of 2 alpha-(2',2'
      disubstituted-hydroxy-ethoxy)tropane (2 alpha-DHET) and its four optical isomers
      with rat cardiac muscarinic receptors was studied. 2 alpha-DHET and its optical
      isomers competitively inhibited the binding of [3H] quinuclidinyl benzilate to
      rat cardiac muscarinic receptors and allosterically decelerated the dissociation
      of bound [3H] quinuclidinyl benzilate in a concentration-dependent manner. The
      rank order of potencies to displace [3H] quinuclidinyl benzilate binding was 1R-2
      alpha-2'R > 1S-2 alpha-2'R > 2 alpha-DHET > 1S-2 alpha-2'S > 1R-2 alpha-2'S,
      while their potencies to decelerate the dissociation of bound [3H] quinuclidinyl
      benzilate were not significantly different. The allosteric potencies were found
      not to be correlated with their binding potencies.

PMID- 7621913
TI  - Receptors for adrenomedullin in human vascular endothelial cells.
AB  - Accumulation of the intracellular cyclic AMP (cAMP) was measured in cultured
      endothelial cells of the human umbilical vein following the incubation with
      adrenomedullin, a newly discovered hypotensive peptide, to determine the presence
      of specific receptors for adrenomedullin. Adrenomedullin increased the
      intracellular cAMP in a dose-dependent fashion in the endothelial cells, and the
      EC50 value was as low as 10(-9) M. Calcitonin gene-related peptide (CGRP) that
      has a homology to adrenomedullin in its amino-acid sequence also increased the
      intracellular cAMP with an EC50 value greater than 10(-7) M. The effect of CGRP
      was attenuated in the presence of CGRP-(8-37), a CGRP receptor antagonist.
      However, CGRP-(8-37) had no effect on the cAMP accumulation by adrenomedullin.
      These findings indicate that the cultured endothelial cells of human umbilical
      vein possess specific adrenomedullin receptors coupled with the adenylate cyclase
      activity that may have little affinity with CGRP.

PMID- 7621912
TI  - Noradrenaline-mediated contractions of ovine uterine artery: role of inositol
      1,4,5-trisphosphate.
AB  - To elucidate the role of inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) as a second
      messenger through which noradrenaline regulates contractions of the uterine
      artery, we present here studies designed to characterize simultaneously the
      noradrenaline-mediated contractions and Ins(1,4,5)P3 formation in isolated
      uterine arteries from near-term pregnant sheep. Noradrenaline stimulated a rapid
      increase of Ins(1,4,5)P3 formation with the peak at 30 second. Simultaneous
      measurement of noradrenaline-induced contractile responses and Ins(1,4,5)P3
      formation revealed a significant linear correlation between these two events. In
      accordance with the contractile results, the noradrenaline-mediated inositol
      phosphate accumulation was blocked by prazosin (0.1 microM), but not by yohimbine
      (0.1 microM). Pre-treatment of tissues with pertussis toxin (200 ng/ml, 3 h)
      failed to block noradrenaline-induced inositol phosphate accumulation. We
      conclude that, in the uterine artery of late pregnancy, the alpha 1-adrenoceptor
      elicited contraction, at least the initial phasic component, is predominantly
      mediated by the formation of Ins(1,4,5)P3, leading to release of Ca2+ from
      intracellular stores.

PMID- 7621914
TI  - Inhibition by folded isomers of L-2-(carboxycyclopropyl)glycine of glutamate
      uptake via the human glutamate transporter hGluT-1.
AB  - The effects of isomers of 2-(carboxycyclopropyl)glycine (CCG) on uptake of L
      glutamate were investigated in COS-7 cells that expressed a cloned human
      glutamate transporter (hGluT-1). The (2S, 3S, 4R)-isomer (L-CCG-III) and the (2S,
      3R, 4S)-isomer (L-CCG-IV) markedly inhibited glutamate uptake with a 50%
      inhibitory concentration of 290 nM and 1.1 microM, respectively. The (2S, 3S, 4S)
      isomer (L-CCG-I) and the (2S, 3R, 4R)-isomer (L-CCG-II) did not inhibit glutamate
      uptake at concentrations of < or = 10 microM. Thus, hGluT-1 showed a markedly
      higher affinity for L-CCG-III and L-CCG-IV with a folded conformation of the
      glutamate skeleton, than for L-CCG-I or L-CCG-II with an extended conformation.

PMID- 7621915
TI  - Dopamine causes stimulation of protein kinase C in rat renal proximal tubules by
      activating dopamine D1 receptors.
AB  - Although it is suggested that in the renal proximal tubules, dopamine D1 receptor
      activation causes inhibition of Na+/K+ATPase via a phospholipase C and protein
      kinase C coupled pathway, the direct stimulation of protein kinase C by dopamine
      has not been reported. The present study was designed to examine the effects of
      dopamine and selective dopamine D1 receptor and dopamine D2 receptor agonists on
      protein kinase C activity. The renal proximal tubule suspensions were obtained
      from male Sprague-Dawley rats. The tubules were incubated separately with
      dopamine and fenoldopam in the presence or absence of dopamine D1 receptor
      antagonist, SCH 23390 ([(R)-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5
      tetrahydro-1H-3- benzazepine]). The protein kinase C activity was measured by
      using a kinase target peptide, conjugated to a fluorescent molecule in water. The
      amino acid sequence of this peptide is, Proline-Leucine-Serine-Arginine-Threonine
      Leucine-Serine-Valine-Alanine- Alanine-Lysine(PKSRTLSVAAK). We found that
      dopamine and fenoldopam [6-chloro-2,3,4,5-tetrahydro-1-(4-hydroxyphenyl)-1H-3
      benzazepine-7,8-di ol] produced concentration-dependent increases in protein
      kinase C activity, which was blocked by SCH 23390. However, the dopamine D2
      receptor agonist, bromocriptine [(5' alpha)-2-bromo-12'-hydroxy-2'-(1-methyl
      ethyl)-5'-(2-methylpropyl)erg o- taman-3',6',18-trione] failed to stimulate
      protein kinase C activity at all the concentrations tested. These results provide
      direct evidence that dopamine stimulates protein kinase C activity via activation
      of dopamine D1 receptors.

PMID- 7621916
TI  - L-2-amino-3-phosphonopropionic acid competitively antagonizes metabotropic
      glutamate receptors 1 alpha and 5 in Xenopus oocytes.
AB  - The aspartate analog 2-amino-3-phosphonopropionic acid (AP3) antagonizes
      glutamate-stimulated phosphatidyl inositide hydrolysis in brain slices, but is
      reportedly weak or ineffective in antagonizing the phosphatidyl inositide-coupled
      cloned metabotropic glutamate receptors 1 alpha and 5. Thus we examined the
      pharmacological properties of AP3 on mGlu1 alpha and mGlu5 receptor responses in
      Xenopus oocytes. DL-AP3 antagonized mGlu1 alpha and mGlu5 responses, but
      antagonism was overcome at high glutamate concentrations consistent with
      competitive inhibition (IC50 = 2.1 mM for mGlu1 alpha). Both responses were also
      inhibited by (RS)-alpha-methyl-4-carboxyphenylglycine (MCPG). We conclude that
      the available antagonists cannot distinguish between the mGlu1 alpha receptor and
      mGlu5 receptor, and that antagonism by AP3 may be obscured in the presence of
      high agonist concentrations or in cells with spare receptors.

PMID- 7621917
TI  - Effects of TCV-116 and CV-11974 on angiotensin II-induced responses in vascular
      smooth muscle cells.
AB  - (+/-)-1-(Cyclohexyloxycarbonyloxy)ethyl 2-ethoxy-1-[[2'-(1H-tetrazol-5
      yl)biphenyl-4-yl]methyl]-1H- benzimidazole-7-carboxylate (TCV-116, Candesartan)
      and its active metabolite 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]
      1H- benzimidazole-7-carboxylic acid (CV-11974) are specific nonpeptide
      angiotensin AT1 receptor antagonists. In the present study, the inhibitory
      potency of these two antagonists on the angiotensin II-induced responses in
      aortic vascular smooth muscle cells from Wystar Kyoto rats was investigated. The
      specific binding of 125I-angiotensin II to cells was inhibited by CV-11974 and
      TCV-116 with a half-maximal inhibitory concentration (IC50) of 3 x 10(-11) M and
      1 x 10(-9) M, respectively. CV-11974 and TCV-116 inhibited the angiotensin II
      induced increase in [3H]thymidine incorporation with an IC50 of 3 x 10(-10) and 5
      x 10(-9) M, respectively. Both CV-11974 and TCV-116 (10(-7) M) completely blocked
      the angiotensin II-induced increase in c-fos mRNA. The inhibitory potency of the
      metabolite CV-11974 was about 30-100-fold higher than that of the prodrug TCV
      116.

PMID- 7621918
TI  - The adenylate cyclase-inhibiting bradykinin receptor in guinea pig ileum
      membranes exhibits an unique antagonist profile.
AB  - The purpose of the present study was to characterize more precisely an
      inhibitory, adenylate cyclase-coupled bradykinin receptor in guinea pig ileum
      membranes. Therefore, the effects of various well-known bradykinin B2 receptor
      antagonists were examined at the level of bradykinin-induced inhibition of ileal
      adenylate cyclase activity and compared with both their binding affinities and
      their potencies to antagonize ileal contraction evoked by bradykinin. A group of
      three highly potent antagonists was found to be able to antagonize both
      bradykinin-induced adenylate cyclase inhibition and smooth muscle contraction.
      Several other antagonists abolished the bradykinin-induced ileal contraction but
      did not influence its action on adenylate cyclase. The compound [D-Nal1, Thi5,8,
      D-Phe7]bradykinin which is known to inhibit the bradykinin-induced contraction in
      the rat uterus but not in the guinea pig ileum was found to be a weak but
      selective antagonist for the adenylate cyclase-coupled bradykinin receptor in
      guinea pig ileum. Altogether, in guinea pig ileum membranes the inhibitory,
      adenylate cyclase-coupled bradykinin B2 receptor with pM affinity towards
      bradykinin exhibits a unique antagonist profile and is distinguished from the
      excitatory bradykinin B2 receptor with nM affinity towards bradykinin.

PMID- 7621919
TI  - CT-scanning and radiographic analysis of temporomandibular joints and
      cephalometric analysis in a case of Herbst treatment in late puberty.
AB  - From a consecutive sample of 100 patients treated with the Herbst appliance after
      the peak of puberal growth, a boy was chosen to show the total effect of the
      Herbst treatment. Changes in the dentofacial morphology and the structure of the
      temporomandibular joints (TMJ) were followed by radiologic examinations and the
      function of the craniomandibular system was studied by clinical examinations, and
      electromyographic and bite-force recordings. Treatment resulted in marked
      dentoalveolar changes, an increase of mandibular length, ramus height, and gonion
      angle. Three months after insertion of the appliance CT-scanning and
      orthopantomograms of the TMJ revealed new bone formation as a double contour in
      the fossa articularis and on the posterior part of the condylar process as a
      result of adaptive bone remodelling. Function was affected by treatment, but was
      markedly restored at control.

PMID- 7621920
TI  - The repair of orthodontic root resorption: an ultrastructural study.
AB  - It has previously been shown by light (LM) and scanning electron microscopy
      (SEM), that after force is terminated, repair of the orthodontic root resorption
      lacunae occur by deposition of new cementum. The ultrastructural details of the
      process are not well established. Since it has been hypothesized that a new
      barrier to protect the root surface is formed during the reparative phase, new
      information on this aspect of orthodontic root resorption may be valuable. The
      aim of the present investigation was, by using transmission electron microscopy
      (TEM), to study in more detail the repair of orthodontic root resorption lacunae
      and the re-establishment of the adjacent periodontal membrane (PM). Three
      experimental tooth movement groups of rats (age 40-45 days) were used. The
      maxillary first molar was moved mesially by a closed coil spring for 10, 14, and
      21 days. The results indicate that transition of active root resorption into a
      process of repair which occurs even in the presence of a light force, is
      associated with invasion of fibroblast-like cells from the circumference into the
      active root resorption site. After 10 days, formation of new tooth supporting
      structures was seen in the periphery of the resorption lacunae, while active
      resorption by multinucleated odontoclast-like cells (OD) took place in the
      central parts. In the later phases, after termination of force, the repair
      process is similar to the early cementogenesis occurring during tooth
      development. New mineralized cementum was observed on the resorbed root surface
      by 21 days. After deposition of the new cementum, the structures of a new
      periodontal ligament (PDL) were comparable with the control specimens.

PMID- 7621921
TI  - The influence of social class, gender, and peers on the uptake of orthodontic
      treatment.
AB  - The accurate prediction of the future demand for orthodontic treatment requires
      an understanding of the factors which influence the uptake of orthodontic
      treatment. This paper examines the influence of social class, gender, and peer
      group on the uptake of orthodontic treatment. A representative random sample
      comprising five-hundred-and-forty 15- and 16-year-old adolescents were
      interviewed in school. The results indicate that familiarity with orthodontic
      appliances among a subject's peer group has a greater influence on the uptake of
      orthodontic treatment than the subject's social class or gender.

PMID- 7621922
TI  - Mandibular function before and after orthodontic treatment.
AB  - To determine the influence of orthodontic treatment on mandibular function, a
      longitudinal study was initiated on 245 consecutive prospective orthodontic
      patients before and after the orthodontic treatment. Of the 245 referred
      patients, eight declined treatment and 27 moved to other parts of the country
      before the treatment was completed. Thus, the longitudinal study was based on 210
      patients. The functional examination was made according to Carlsson and Helkimo
      (1972) and Helkimo (1974), and by the same person (MO). Before the orthodontic
      treatment, symptoms of temporomandibular disorders (TMD) were found in 16.7 per
      cent of the patients and in 6.7 per cent after treatment. The number of subjects
      without signs or symptoms of TMD increased from 26.7 per cent before treatment to
      46.2 per cent after. According to the dysfunction index (Helkimo, 1974), 31.4 per
      cent of the patients had a moderate and 13.8 per cent a severe mandibular
      dysfunction before the start of orthodontic treatment. After the treatment, the
      corresponding figures were 14.3 and 5.7 per cent, respectively. The material was
      divided into groups, consisting of boys and girls younger than 13 years, and 13
      years and older at the start of treatment. Before treatment there was a higher
      prevalence of signs and symptoms of TMD in the older age group than in the
      younger, and higher in girls than in boys. After the orthodontic treatment, the
      prevalence was still higher in girls than in boys in both age groups, but not
      higher in the older age group than in the younger group.

PMID- 7621923
TI  - Tensor analysis of facial growth in males.
AB  - This longitudinal study examines in detail the facial development of 18
      untreated, male children with acceptable occlusions. The children were examined
      in the prepubertal period (age range 7-10 years) and again in their late teens
      (15-19 years of age). A tensor analysis, which permits the computation of
      differences in form (that is in size and shape) without specifically measuring
      either, was employed to describe the facial changes which occurred during this
      time interval. Values for the x and y co-ordinates of 16 hard and four soft
      tissue landmarks were determined at each stage. Customized software allowed both
      graphical and numerical examination of the mean changes over time between 28
      triads of points, covering skeletal, dental, and soft tissue elements. The
      analysis confirmed previous work in describing facial change but was more
      sensitive than conventional cephalometry, especially where landmarks were
      evaluated outside the traditional sella-nasion framework.

PMID- 7621924
TI  - Cluster analysis application to Class I malocclusion.
AB  - The purpose of this study was to obtain Class I malocclusion statistical subtypes
      by applying cluster analysis techniques, to assess clinical and cephalometric
      characteristics from different clusters, and to analyse sex and age effects on
      grouping patterns. Four-hundred-and-sixteen Spanish patients (243 females, 173
      males) with Class I osseous and dental malocclusion (4 degrees > ANB > 0 degrees)
      between 8 and 16 years of age, with no previous orthodontic treatment, were
      analysed. Cluster analysis was applied to the information provided by 20
      variables both clinical and cephalometric (Ricketts' analysis) per patient. The
      grouped individuals were defined in a statistically significant manner by a
      greater lower incisive proclination, greater lower labial protrusion, less dental
      crowding, and less pogonion-NB distance. So, only the protrusive traits were
      statistically expressed in the cluster analysis. The grouping pattern in Class I
      malocclusion was shown in a more defined form at younger age levels and
      disappeared with age. The clustering pattern was very similar in Class I
      malocclusion males and females.

PMID- 7621925
TI  - Dentofacial changes in Norwegian and Iowan populations between 6 and 18 years of
      age.
AB  - The purpose of this study was to compare the dentofacial changes in Norwegian and
      Iowan populations between 6 and 18 years of age. Comparisons of the absolute and
      incremental changes were made both longitudinally and cross-sectionally. The
      Norwegian sample consisted of 39 females and 35 males, the Iowa sample consisted
      of 15 females and 20 males, for whom complete sets of data were available for the
      period of the study. All subjects had a clinically acceptable occlusion and had
      not undergone previous orthodontic treatment. Descriptive statistics summarized
      the changes in 29 parameters. Longitudinal comparison of the growth curves
      evaluated the curve profiles and curve magnitudes for the two populations for
      both males and females. The analysis of variance was also used to compare the
      absolute and incremental changes at ages 6, 9, 12, 15, and 18 years. The study
      resulted in the following findings: 1. The longitudinal growth profile
      comparisons of the various dentofacial parameters indicated that the growth
      trends of the Norwegian and Iowa groups were essentially similar. 2. The
      comparisons of the growth profiles of the males and females from the two
      populations also indicated that there were no significant differences between the
      shape of their growth curves. 3. The comparisons of the curve magnitude, as well
      as the results of the cross-sectional comparisons, indicated that Norwegians had
      significantly greater maxillary and mandibular protrusion, and larger
      proclination of the upper and lower incisors than the Iowans.

PMID- 7621926
TI  - A preliminary report on lower arch crowding in the mature adult.
AB  - Changes in lower arch crowding were measured on models of 16 subjects between the
      ages of 18 and 50 years. Changes in position of various cephalometric points
      relative to the skull base were measured on 90-degree left lateral cephalograms.
      Some increase in lower arch crowding was found in 80 per cent of subjects. With
      one exception, all subjects showed changes in size and orientation of the jaws
      relative to the skull base varying in amount and direction. Possible causes of
      increased lower arch crowding in the mature adult are discussed.

PMID- 7621927
TI  - Task dependence of primate arm postures.
AB  - We studied the relations between arm posture and hand location as monkeys
      performed tasks involving three-dimensional arm movements. Two specific questions
      were addressed: how reliable are these relations from trial to trial and from day
      to day, and are the arm postures dictated only by the location of the hand or are
      the postures also dependent on the task being performed? Based on the variable
      errors in linear regressions, we found that monkeys performed the tasks in a very
      stereotypic fashion from trial-to-trial: for a given monkey and task, knowing the
      position of the hand was sufficient to determine the posture of the arm. These
      relations did not change from day to day; the relation between hand location and
      posture was stable over the course of the experiments. In some of the tasks, the
      postures employed by the monkeys were strikingly similar to those observed in
      human psychophysical studies. The relations between hand location and arm posture
      exhibited a large degree of task dependence. Changing the required orientation of
      the hand resulted in changes in the arm posture.

PMID- 7621928
TI  - Adapting to monocular vision: grasping with one eye.
AB  - The aim of the present study was to determine whether normal subjects with one
      eye covered and patients in whom one eye had been enucleated generate more head
      movements than subjects using binocular vision during the performance of a
      visually guided grasping movement. In experiment 1, 14 right-handed normal
      subjects were tested binocularly and monocularly in a task in which they were
      required to reach out and grasp oblong blocks of different sizes at different
      distances. Although the typical binocular advantage in reaching and grasping was
      observed, the overall head movement scores did not differ between these testing
      conditions. In experiment 2, seven right-handed enucleated patients were compared
      to seven age and sex-matched control subjects (tested under binocular and
      monocular viewing conditions), on the same task as used in experiment 1. While no
      differences were found in the kinematics of reaches produced by the enucleated
      patients and the control subjects, the patients did produce larger and faster
      resultant head movements, composed mainly of lateral and vertical movements. This
      suggests that enucleated patients may be generating more head movements in order
      to better utilize retinal motion cues to aid in manual prehension.

PMID- 7621930
TI  - Non-length-tuned cells in layers II/III and IV of the visual cortex: the effect
      of blockade of layer VI on responses to stimuli of different lengths.
AB  - We have previously shown, using a local inactivation technique, that layer VI
      provides a facilitatory input to the majority of hypercomplex cells located in
      layer IV above, and hence to layers II/III, which in many cases enhances length
      selectivity. However, many cells in these layers are not tuned for stimulus
      length, being equally responsive to long and short stimuli. Thus it is important
      to known whether layer VI can influence the responses of these cells. We have now
      used a similar paradigm of iontophoretic application of GABA to examine the
      effect of blockade of layer VI on the length tuning profiles of these cells in
      layers II-IV. During the blockade of layer VI, the most common effect, seen in
      41% of the cells, was inhibition of visual responses, (i.e. commensurate with
      loss of a facilitatory input). An increase in response magnitude was found in 21%
      of the population, and responses were unaffected in 36% of cells tested. This
      suggests that the predominant influence of local regions of layer VI on this cell
      type, located in layers II/III and IV, is facilitatory, with a smaller proportion
      of cells receiving an inhibitory input. Such effects were seen even with the
      shortest lengths tested, suggesting once more that elements of layer VI are
      responsive to stimuli much shorter than was previously accepted. Thus these data
      suggest that layer VI plays a role in the generation of the response dynamics of
      non-length-tuned cells in overlying layers II/III and IV.

PMID- 7621929
TI  - Influence of handedness on motor unit discharge properties and force tremor.
AB  - Discharge properties of motor units (MUs) in the first dorsal interosseous muscle
      (FDI) were studied in the dominant and non-dominant hands of six right-handed
      (RH) and six left-handed (LH) individuals. MU discharge rates and variability
      were similar in each hand in RH (186 MUs) and LH (160 MUs) subjects. MU
      synchronization was less prominent in the dominant hand of RH subjects, with 51%
      (45/88) of cross-correlograms of MU discharge having significant central peaks,
      compared with 81% (90/111) for the non-dominant hand. The strength of MU
      synchronization (expressed as the frequency of extra synchronous discharges above
      chance) was weaker in the dominant hand of right-handers (0.23 +/- 0.03 s-1 vs
      0.39 +/- 0.03 s-1), and synchronous peaks from that hand were slightly broader.
      Four of six RH subjects had significant differences in synchronization between
      hands (weaker in dominant hand). In contrast, left-handers had similar incidence
      (80 vs 82%, n = 161) and strength (0.41 +/- 0.03 s-1 vs 0.37 +/- 0.03 s-1) of MU
      synchrony in dominant and non-dominant hands. No LH subject had a significant
      difference in synchronization between hands. Force tremor was quantified in each
      hand in the same subjects during isometric abduction of FDI at 0.5 N and 3.5 N,
      and directly correlated with the extent of MU synchronization in the muscle.
      Tremor root mean square amplitude was similar in dominant and non-dominant hands.
      Power spectral analysis of the tremor force revealed that the peak frequency in
      the power spectrum was not influenced by handedness, but power at the peak
      frequency was higher in the non-dominant hand of RH subjects. Correlations
      between MU discharge variability and synchrony with measures of tremor amplitude
      were weak. The reduced MU synchronization in the dominant hand of right-handers
      may reflect a more restricted distribution of direct projections from motor
      cortical neurons within the FDI motoneuron pool, or reduced excitability of the
      cortical neurons during the task. These differences in MU synchronization,
      however, had an insignificant influence on the magnitude of physiological tremor
      in the FDI.

PMID- 7621931
TI  - Persistent mirror movements: force and timing of "mirroring" are task-dependent.
AB  - A simple isometric motor task was used to quantify intended and unintended finger
      movements in two subjects (father and son) with persistent mirror movements. One
      hand voluntarily changed grip force between thumb and index finger at different
      amplitudes and frequencies, while the other hand was to maintain a constant
      force. During all experimental conditions the "steady" hand showed
      insuppressible, highly cross-correlated contractions, compatible with bilateral
      distribution of a single motor command to the spinal cord. However, these
      associated movements were not strictly mirror images, nor did they show a fixed
      relationship to the voluntary movements across experimental conditions. The ratio
      of mirror to voluntary movement ranged from 1.4 to 19.1% and from 3.4 to 78.4% in
      the two subjects and was directly related to voluntary strength and speed. At
      maximum speed, mirror activity tended to precede voluntary activity, while it was
      delayed in slow force changes. Comparable time lags were not found in control
      subjects instructed to simulate mirror movements. We conclude that neuronal
      mechanisms in addition to bilateral corticomotoneuronal connections are at work
      in persistent mirror movements.

PMID- 7621932
TI  - Scalp topography and analysis of intracranial sources of face-evoked potentials.
AB  - Several reports have described that a positive vertex peak of an evoked potential
      varied in amplitude and latency specifically when images of faces were the
      eliciting stimulus. The scalp topography and the possible underlying dipole
      sources of this peak are the subject of this report. We presented black-and-white
      photographs of human faces, flowers and leaves to 16 healthy subjects and
      recorded the evoked brain potentials from 31 scalp electrodes. We found the
      previously described higher amplitude of the positive vertex peak when faces were
      the crucial stimulus, but the latency of this peak was the same (180 ms) for all
      three categories of stimulus. At the posterior temporal electrodes, the face
      waveforms showed a negative peak at 175 ms, which was only rudimentary in the
      waveforms elicited by the other stimuli. Since in most previous reports a mastoid
      reference was used, it is most likely that the previously described latency shift
      of the positive vertex peak associated with face stimuli was due to the
      interaction with this posterior temporal peak. The dipole analysis of the
      possible generators of the recorded potentials suggested the sequential
      activation of occipital, lateral temporal and mesio-temporal brain structures
      during the perception of a human face.

PMID- 7621933
TI  - Source analysis of magnetic field responses from the human auditory cortex
      elicited by short speech sounds.
AB  - We made a detailed source analysis of the magnetic field responses that were
      elicited in the human brain by different monosyllabic speech sounds, including
      vowel, plosive, fricative, and nasal speech. Recordings of the magnetic field
      responses from a lateral area of the left hemisphere of human subjects were made
      using a multichannel SQUID magnetometer, having 37 field-sensing coils. A single
      source of the equivalent current dipole of the field was estimated from the
      spatial distribution of the evoked responses. The estimated sources of an N1m
      wave occurring at about 100 ms after the stimulus onset of different
      monosyllables were located close to each other within a 10-mm-sided cube in the
      three-dimensional space of the brain. Those sources registered on the magnetic
      resonance images indicated a restricted area in the auditory cortex, including
      Heschl's gyri in the superior temporal plane. In the spatiotemporal domain the
      sources exhibited apparent movements, among which anterior shift with latency
      increase on the anteroposterior axis and inferior shift on the inferosuperior
      axis were common in the responses to all monosyllables. However, selective
      movements that depended on the type of consonants were observed on the
      mediolateral axis; the sources of plosive and fricative responses shifted
      laterally with latency increase, but the source of the vowel response shifted
      medially. These spatiotemporal movements of the sources are discussed in terms of
      dynamic excitation of the cortical neurons in multiple areas of the human
      auditory cortex.

PMID- 7621934
TI  - The organization of patterns of multilimb coordination as revealed through
      reaction time measures.
AB  - Simple visual reaction time (RT) during the performance of sagittal movements of
      the upper and/or lower limbs was investigated. Experiment 1 demonstrated that RTs
      increased when more limbs were to be moved simultaneously. This effect was more
      apparent for the upper than for the lower limbs. Experiment 2 allowed a
      separation of RT into premotor time (PMT) and motor time (MOT) components through
      analysis of electromyographic activity, and showed that these longer response
      delays were associated with increased PMTs. This suggests that the time required
      for the central organization of movements increased as more limbs were to be
      controlled simultaneously. Compared to single-limb performance conditions, the
      increases in RT were much larger in the upper limbs (up to 16%) than in the lower
      limbs (up to 5%) when limb segments were added. During single-limb conditions,
      RTs in the upper limbs tended to be smaller than in the lower limbs, in
      accordance with efferent nerve conduction time estimates. Conversely, the lower
      limb(s) was (were) initiated before the upper limb(s) when both effector types
      were moved simultaneously. This pattern of activation is reminiscent of the
      organization of postural control during upright standing, where goal-directed arm
      activity is preceded by (bilateral) leg activity to anticipate for the upcoming
      postural destabilization. Finally, hemifield manipulations in experiment 2
      revealed faster RTs and PMTs for stimuli presented in the right visual field in
      comparison with the left field. This advantage was evident for ipsilateral as
      well as contralateral responses and supports the pre-eminence of the left
      hemisphere in the complex organization of gross motor responses.

PMID- 7621935
TI  - Effects of transcranial magnetic stimulation over the region of the supplementary
      motor area during sequences of memory-guided saccades.
AB  - Transcranial magnetic stimulation (TMS) over the region of the supplementary
      motor area (SMA) was used to study the cortical control of sequences of memory
      guided saccades. In ten healthy subjects, TMS was applied during (a) the target
      presentation (learning) phase, (b) the memorization phase, and (c) the execution
      phase of such saccade sequences. Stimulation during the presentation phase
      resulted in a significant increase in errors, compared to the results without
      stimulation. In contrast, stimulation during the memorization or execution phases
      had no significant influence on the performance of these sequences. The effect of
      TMS during the presentation phase seems to be specific for an interaction with
      the SMA function, since, in a control experiment with TMS of the occipital cortex
      during the same phase, the results were similar to those without stimulation. It
      is hypothesized that different cortical areas are involved in the learning,
      memorization and execution of sequences of memory-guided saccades. The SMA action
      could be crucial during the learning phase, but not during the memorization and
      execution phases of such sequences.

PMID- 7621936
TI  - Progressive decrease in heteronymous monosynaptic Ia facilitation with human
      ageing.
AB  - To evaluate functional change in the spinal reflex pathway with ageing, we
      studied heteronymous Ia facilitation from the quadriceps to soleus muscle in 30
      normal volunteers (aged 24-68 years). The size of the test H-reflex of the soleus
      muscle was adjusted to 25% that of the maximal M-response. The conditioning
      stimulus was adjusted to 1.5-fold the motor threshold to stimulate all the Ia
      fibres in the femoral nerve. Facilitation was quantified as the slope of the very
      early part of facilitation, within 0.8 ms of onset. This procedure enabled us to
      evaluate the extent of monosynaptic Ia facilitation without contamination by
      other effects. The extent of facilitation decreased linearly with age. This
      decrease in facilitation could reflect a decrease in the number of Ia fibres and
      in their conduction velocities, and an increase in presynaptic inhibition on Ia
      terminals. The increase in presynaptic inhibition may be an adaptive phenomenon
      in the ageing of the neuromuscular system or, alternatively, a deteriorating
      process with decreasing flexible supraspinal modulation.

PMID- 7621937
TI  - Differences in the temporal dynamics of the visual ON and OFF pathways.
AB  - The temporal structure of spike trains recorded from optic fibers and single
      units of the lateral geniculate nucleus (LGN) and primary visual cortex of the
      cat was studied with a novel method of inter-spike interval analysis. ON type
      relay cells of the LGN exhibited a multimodal interval distribution preferring a
      distinct interval (fundamental interval) and its multiples during the sustained
      light response, whereas most OFF cells showed a broad, unimodal distribution. The
      general pattern of the interval distribution was relatively independent of
      stimulus size and contrast and the degree of light adaptation. Simultaneously
      recorded S-potentials originating from the retinal input generally produced only
      a single peak at the fundamental interval length. Therefore, the multimodal
      interval distribution of LGN cells seems to be a result of intra-geniculate
      inhibition. Cortical cells also showed a weak tendency to fire with spike
      intervals similar to LGN cells. Therefore, the regular firing pattern observed at
      peripheral stages of the visual pathway can persist at higher levels and might
      promote the occurrence of oscillatory activity.

PMID- 7621938
TI  - Fos-related protein expression in the midline paraventricular nucleus of the rat
      thalamus: basal oscillation and relationship with limbic efferents.
AB  - The expression of Fos-related protein, encoded by the proto-oncogene c-fos, was
      investigated by means of immunohistochemistry in the paraventricular nucleus of
      the thalamic midline (PV) during nighttime and daytime in rats entrained to a 12
      h light/12-h dark cycle. In the first step of this study the animal's
      physiological state preceding perfusion was monitored with electro
      encephalographic recording. It was thus detected that the PV contained a
      considerable number of Fos-like-immunostained neurons during the hours of
      darkness, when the rats had been awake, and that the number of Fos-like
      immunoreactive neurons was significantly lower during the hours of light, after a
      period of sleep. In the second step of this study Fos immunohistochemistry was
      combined with the retrograde transport of a gold-labeled tracer injected either
      in the amygdala or in the nucleus accumbens. This strategy enabled us to
      determine that in the rats perfused during nighttime Fos-related protein was
      spontaneously induced in PV cells projecting to these targets, with a significant
      prevalence of neurons projecting to the amygdala in the anterior portion of the
      PV and of neurons projecting to the nucleus accumbens in the posterior part of
      the nucleus. In addition, a significant reduction of Fos-like-immunoreactive
      cells was detected in the PV ipsilaterally to the injection, indicating that
      tracer administration and axonal transport may interfere with c-fos expression in
      neurons. Altogether the present data indicate that Fos-related protein expression
      undergoes a marked oscillation in the PV during 24 h in basal conditions, and
      that c-fos is induced in the PV relay neuronal subsets when the animal is
      awake.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7621939
TI  - Binaural noise stimulation of auditory callosal fibers of the cat: responses to
      interaural time delays.
AB  - The corpus callosum, the principal neocortical commissure, allows for the
      interhemispheric transfer of lateralized information between the hemispheres. The
      aim of the present experiment was to study callosal transfer of auditory
      information in the cat, with particular reference to its contribution to sound
      localization. The corpus callosum was approached under direct visual control, and
      axonic responses were recorded under light anesthesia using glass micro-pipettes.
      Results showed that auditory information is transmitted in the posterior portion
      of the callosum. Diotic presentations, in which interaural time delay was
      manipulated, indicated that, for a large number of fibers, the largest excitatory
      or inhibitory interactions were obtained at null interaural time delay, a
      condition which supports the notion of a callosal contribution to auditory
      midline fusion. However, an important number of callosal fibers was also found to
      be excited maximally at specific, non-zero interaural time delays, suggesting
      that they preferred sounds situated at spatial locations other than the midline.
      The results are discussed in relation to those obtained electrophysiologically
      for the visual and somesthesic modalities and in terms of results obtained in
      human and animal behavioral experiments.

PMID- 7621943
TI  - Dynamic differentiation of GABAA-sensitive influences on orientation selectivity
      of complex cells in the cat striate cortex.
AB  - The influence of GABAA receptors on orientation selectivity of cat complex cells
      was tested by iontophoresis of the GABAA receptor blockers bicuculline and N
      methyl-bicuculline while stimulating with drifting sinusoidal gratings. Reduction
      of orientation tuning was markedly less than reported in previous studies that
      used drifting bars as visual stimuli. Only 3/31 cells lost orientation
      selectivity, with an average increase in bandwidth of 33%, as opposed to half the
      cells losing selectivity and a bandwidth increase for the remainder of 47% as
      reported previously. Infusion of GABAA blockers revealed a prominent stimulus
      onset transient response, lasting about 120 ms, that showed a broadening of
      orientation selectivity comparable to that found using drifting bars under
      similar circumstances. We believe that drifting gratings emphasize a steady-state
      response component that retains, in the presence of GABAA blockers, significant
      orientation selectivity. Because the onset transient is initially unselective for
      orientation, we suggest that the steady-state, orientation-selective response
      component develops from an alternate inhibitory mechanism, possibly mediated by
      GABAB receptors.

PMID- 7621940
TI  - Vibrissal motor cortex in the rat: connections with the barrel field.
AB  - The flow of information in the sensorimotor cortex may determine how somatic
      information modulates motor cortex neuronal activity during voluntary movement.
      Electrophysiological recordings and neuroanatomical tracing techniques were used
      to study the connections between the primary somatosensory cortex (SI) and the
      vibrissal representation of the primary motor cortex (MI) in rodents.
      Intracortical microstimulation (ICMS) was applied to the vibrissal region of the
      motor cortex to identify a site from which stimulation evoked movements of the
      vibrissae. Movements of only a single whisker were evoked by applying low
      intensity stimulating current to particular locations within MI. A single
      injection of either horseradish peroxidase (HRP) or biocytin was made at the
      stimulus site in each animal, to retrogradely label cells in the somatosensory
      cortex. Receptive field (RF) responses were recorded from neurons in the barrel
      cortex to identify the sensory cortex representation of the same whisker that
      responded to ICMS. The site at which neurons responded predominately to manual
      stimulation of this particular vibrissa was marked by a small electrolytic
      lesion. The projection from the somatosensory cortex to the identified whisker
      representation in the motor cortex was determined by mapping the location of
      labeled neurons in tissue sections processed for either HRP or biocytin. The
      relationship of the labeled cells in SI to the barrel structures was determined
      from adjacent sections that were stained for cytochrome oxidase. In all cases,
      the barrel column associated with the relevant whisker contained labeled cells.
      Surrounding barrels also contained labeled cells, although fewer in number. Very
      few labeled cells were found in non-contiguous barrels. These results show that
      the SI to MI projection is somatotopically arranged, such that the sensory cortex
      representation of a whisker is morphologically connected to the motor cortex
      representation of the same whisker. Thus, sensory information is relayed to MI
      from the relevant whisker region in SI. Adjacent whisker regions also appear to
      relay somatic input, but presumably to a lesser degree. A second group of animals
      received single small injections of the anterograde tracer, Phaseolus vulgaris
      leucoagglutinin, to an electrophysiologically identified whisker representation
      in the sensory cortex. A single narrow column of labeled fibers was found in the
      motor cortex following such injections. Thus, the sensory cortex appears to relay
      somatic information from the vibrissae to restricted regions of the motor cortex
      in a somatotopically organized manner. Furthermore, the stimulus-evoked whisker
      movements suggest that certain features of the output map of the motor cortex are
      discretely organized.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7621941
TI  - Paradoxical enhancement of long-term potentiation in poor-learning rats at low
      test stimulus intensities.
AB  - Much empirical evidence and numerous theoretical models point to modification of
      synaptic efficacy as a mechanism for memory formation. To evaluate theoretical
      models, it is necessary to obtain quantitative experimental data relating
      learning to experimentally induced synaptic efficacy changes (such as long-term
      potentiation, LTP). An important problem in this type of experiment is how to
      quantify the LTP induced by a given stimulation protocol. Of relevance is the
      informally well-known observation that LTP magnitude appears to vary as a
      function of the intensity of the stimulus used to evoke baseline responses. The
      present study found that using a measure of LTP that circumvents this variation,
      a strong negative correlation of learning with potentiation emerges. Spatial
      learning ability was compared with the magnitude of subsequent LTP induction as
      follows: rats underwent a day of spatial training in a watermaze followed by 5
      days of bilateral perforant path tetanisation. Baseline electrophysiological
      responses were evoked over a range of stimulus intensities (input/output [IO]
      curves) before and after tetanisation. Although LTP was observed across the whole
      of the IO curve, it showed a smooth decline with increasing current. The animals
      were then grouped according to their watermaze performance and IO curves compared
      between good and poor learners. After tetanisation, there was a negative within
      animal correlation between learning and evoked potential size with weak test
      stimuli and a positive correlation with strong stimuli. The decline of LTP across
      the IO curve differed between good and poor spatial learners; the poor learners
      showed higher percentage potentiation with test stimuli close to zero intensity,
      but a faster decrease in LTP across the curves. The findings are therefore: (1)
      the measured amount of LTP declined systematically with increasing stimulus
      strength, and (2) the parameters of the decline correlated with spatial learning
      ability. These results raise two important issues. First, because measured LTP
      varied systematically across the IO curve, it appears that for quantitative
      analyses the widely used method of LTP measurement using a single test stimulus
      intensity risks missing significant features of the data. It is suggested that a
      measure be used that incorporates data from a range of stimulus intensities.
      Second, when such a measure is used there is a striking negative correlation of
      spatial learning ability with LTP. These apparently paradoxical results are
      discussed.

PMID- 7621942
TI  - Different patterns of fore-hindlimb coordination during overground locomotion in
      cats with ventral and lateral spinal lesions.
AB  - The effect of large, low thoracic (T10-T11), partial spinal lesions involving the
      ventral quadrants of the spinal cord and, to a different extent, the dorsolateral
      funiculi, on fore-hindlimb coordination was examined in cats walking overground
      at moderate speeds (40-100 cm/s). Three different forms of impairment of fore
      hindlimb coordination depending on the extent of the lesions, were observed.
      Lesions sparing the dorsolateral or the ventral funiculus on one side preserved
      the equality of the fore- and hindlimb locomotor rhythms but changed the coupling
      between the movements of both girdles as compared to intact animals. Larger
      lesions in which, in addition to the ventral quadrants of the spinal cord, also
      major parts of the dorsolateral funiculi were destroyed elicited episodes of
      rhythm oscillations in both girdles, which appeared at the background of a small
      difference in these rhythms. Lesions destroying almost the whole spinal cord
      induced a permanent difference (about 200 ms) in the step cycle duration of the
      fore- and the hindlimbs. However, even in these animals some remnant form of fore
      hindlimb coordination was found. The results suggest that dorsolateral funiculi
      play a major role in preserving the equality of rhythms in the fore- and the
      hindlimbs, while lesions of the ventral quadrants change the coupling between
      limbs.

PMID- 7621944
TI  - Central control of reciprocal inhibition during fictive dorsiflexion in man.
AB  - The size of the soleus Hoffmann reflex (H-reflex) was measured in six healthy
      human subjects before and after transmission in the common peroneal nerve (CPN)
      was blocked reversibly by local injection of lidocaine. It was found that the H
      reflex at rest increased after the block. When the subjects attempted to perform
      a dorsiflexion while the CPN was blocked ("fictive dorsi flexion"), the soleus H
      reflex was strongly depressed. Stimulation of the CPN proximal to the block
      elicited a short-latency inhibition of the soleus H-reflex, which was probably
      mediated by reciprocal Ia interneurones. This inhibition never increased during
      dorsiflexion relative to rest prior to the CPN block, but after the block a
      significant increase in inhibition was seen during fictive dorsiflexion in three
      subjects. Stimulation of the femoral nerve (FN) elicited a short-latency
      monosynaptic Ia facilitation of the soleus H-reflex. This facilitation was found
      to decrease during dorsiflexion relative to rest before the block as well as
      during fictive dorsiflexion after the block. The decrease in the H-reflex during
      fictive dorsiflexion demonstrates that although an increased Ia-afferent feedback
      via the gamma-loop may contribute to reciprocal inhibition when transmission in
      the CPN is intact, a noticeable, centrally mediated inhibition may occur in the
      absence of this feedback. It is suggested that this inhibition is caused by
      central facilitation of interneurones mediating disynaptic Ia inhibition as well
      as interneurones mediating presynaptic inhibition of Ia afferents.

PMID- 7621945
TI  - [Interleukin-1 production by exudate and bone marrow macrophages in experimental
      acute infectious peritonitis].
AB  - The model of acute infectious peritonitis in mice has been used to show that
      inflammation is attended by a marked phasic increase in interleukin-1 (IL-1)
      production by macrophages of exudate and bone marrow. The increased IL-1
      production by macrophages of exudate proceeds earlier than that by macrophages of
      the bone marrow. This indicates that activation of the bone marrow macrophages
      may be a result of the effect of OL-1 and other haemopoietic factors released by
      macrophages on the inflammatory focus.

PMID- 7621946
TI  - [The prophylactic action of carnitine in acute hemic hypoxia].

PMID- 7621947
TI  - [The lysosomal acid phosphatase activity of the peripheral blood neutrophilic
      leukocytes in inflammation].
AB  - The investigation was carried out on 56 adult rabbits. The level of activity of
      lysosomal acid phosphatase in blood, its dependence on a degree of degranulation
      of granulocytes and interaction of these processes on parametres of some humoral
      systems of blood controlled by the Hageman factor were investigated under
      conditions of aseptic inflammation caused by intramuscular injection of
      formaline. The conclusion is made that exocytosis of lysosomal enzymes and
      changes in activity levels of some humoral systems controlled by them under
      conditions of inflammation are nonspecific components of a general adaptation
      syndrome.

PMID- 7621948
TI  - [The dynamics of the level of antiprotein antibodies in the recipient blood serum
      under different conditions of the passive inoculation of rabbits with allogeneic
      antiprotein blood preparations].
AB  - Dynamics of the content of antiproteic antibodies in the recipient blood serum
      was studied during intravenous and intramuscular passive immunization with
      allogenic antiproteic blood preparations. Experiments were carried out on 98
      Chinchilla rabbits. Doses of the injected preparation, specific antibodies titres
      and the number of injections were varied. The schemes of application of
      antiproteic plasma and antiproteic immunoglobulin are presented.

PMID- 7621949
TI  - [Oxygen-dependent processes in the irradiated organism].
AB  - Interaction of oxygen with the X-rayed tissues, chemical substances and elements
      is one of the main mechanism of radioactive damage. Radiosensibilization by
      oxygen (oxygen effect) is most highly exhibited under the action of high and
      moderate radiation doses. However there is only scanty investigations and
      information about oxygen-dependent processes under low doses of internal and
      external radiation due to their intricate character. Radiation exerts also a
      great influence on oxygen metabolism and oxygen consumption level. Oxygen takes
      active part in post-radiation recovery both at the level of molecules,
      organelles, cells, tissues, organs and the organism on the whole. The partial
      pressure of oxygen and its content have a great influence on the action of
      radioprotectors, anti-radiation therapy and healing methods. Long-term influence
      of hypoxia at high altitude evokes adaptation changes, stimulates recovery
      processes in an X-rayed organism, increases resistance to radiation and other
      noxious factors.

PMID- 7621951
TI  - [Experimental research on the adaptogenic properties of Kryms'kyi balsam].
AB  - The effect of balsam "Kryms'kyi" has been studied in chronic experiments on
      Wistar rats. It is proved that peroral administration of balsam "Kryms'kyi" to
      rat for 4-7 days enhances excretion of 17-KC, static and dynamic muscular
      workability, resistance to hypoxia, accelerates elimination of xenobiotics,
      decreases stress-induced damages of the stomach mucosa, myocardium and
      lymphopenia. This permits considering the balsam an adaptogen and recommending it
      for clinical test.

PMID- 7621950
TI  - [The hormonal regulation of thymus activity in threatened abortion].
AB  - It is stated that in women with the abortion threat at any term of gestation (I,
      II, III trimesters) the endocrine function of the thymus essentially increases.
      The role of hormones in the thymic activity disorder is studied. It is shown that
      insufficiency of the functional activity of the trophoblast ranks first in the
      mechanism of hormonal regulation of thymic endocrine function in nonbearing of
      pregnancy. The other significant reason of an essential increase in the titer of
      thymic serum factor (TFS) is a disorder in interconnections inside the
      hypophyseal-adrenal system. Determination of TFS and the above hormonal indices
      can be used as the prognostic test of the pregnancy course.

PMID- 7621952
TI  - [The effect of insulin on cardiac activity and on the coronary and systemic
      circulations].
AB  - The studies were performed on healthy closed-chest chloralose-anaesthetized dogs
      using catheterization, extracorporal perfusion and resistography of coronary
      arteries and catheterization and continuous drainage of the coronary sinus.
      Insulin (0.1 and 1.0 IU/kg, i.v.) injected to healthy animals produced dose
      dependent biphasic cardiohaemodynamic reactions. The first phase of the reaction
      includes transient (5-10 min) cardiac function strengthening, coronary arteries
      constriction, heart rate acceleration, myocardial oxygen consumption elevation,
      coronary sinus blood pH elevation and pO2 decrease. After that there arises more
      prolonged and constant dilation of coronary arteries reduction of the cardiac
      function, slowing of the heart rate, lowering of the myocardial oxygen
      consumption, decrease of cardiac venous blood pH and increase of pO2, reduction
      of T waves magnitude and ST segments shifts both in standard and breast leads.
      The second phase of the reaction is either attenuated or even absent after
      blockade of beta-adrenoceptors (propranolol, 0.5 mg/kg, i.v.). The results
      indicate that insulin effects on cardiohaemodynamics are realized through the
      interaction between insulin and heart and vessels of the adrenergic system.

PMID- 7621953
TI  - [A comparison of the contractile properties of the muscles of the lower
      extremities in man].
AB  - The physiological features of two antagonistic muscle groups, the dorsiflexors
      and plantar flexors of the ankle, have been compared in 11 healthy subjects aged
      15-17 years (+/- SE; 16 +/- 1.2 years). Contractile properties of plantar flexors
      of the foot, namely of tibialis anterior (TA) and extensors triceps surae (TS)
      have been estimated by mechanical parameters of voluntary and electrically evoked
      contractions. All test subjects exhibited tolerance to supramaximal force of
      electric stimulation of n. tibialis and n. peroneus profundus at a frequency of
      150 impulses.s-1 (for TS) and 150 impulses.s-1 and 250 impulses.s-1 (for TA). TA
      displayed high velocity and force-velocity properties (p < 0.05-0.001); TS had
      high force parameters (p < 0.05-0.01). The magnitude of force deficiency observed
      during voluntary contraction of these muscles is lower in TA and higher in TS (p
      < 0.05). The results permit supposing that differences in contractile properties
      of the muscles under study depend on a various specific contribution of
      peripheral and CNS factors.

PMID- 7621954
TI  - [The vitamin and trace element status of the personnel of the Chernobyl Atomic
      Electric Power Station and of preschool children in the city of Slavutich].
AB  - Supply of the Chernobyl NPP staff and Slavutich children with vitamins and
      minerals has been examined in spring 1992. From 43 to 100% of people have
      moderate deficiency of vitamin C, B1, B2, B6 and folic acid, 6-61%--deep
      deficiency of these nutrients. Most of the people have insufficient supply with
      vitamins in the form of polyhypovitaminosis, i.e. combined deficiency of ascorbic
      acid and of 2 or 3 vitamins of the B group. Deficiency of 2 vitamins was found in
      20% of adults of 3 vitamins in 37%, of 4 vitamins in 29% and of 1 vitamin in 10%
      of adults. Only 4% of examined adults are sufficiently supplied with all vitamins
      and none of children. Deficiency of 1 vitamin was found in 11% of children, of 2
      vitamins in 15%, of 3 vitamins in 17%, of 4 vitamins in 35%, of 5 vitamins in 20%
      and of 6 vitamins in 2% of children. Supply of children with all vitamins has
      been improved when they received combined vitamin-mineral preparation "Duovit"
      for one month. Universal prophylactic vitaminization by means of administration
      of ascorbic acid and polyvitamin preparations in doses corresponding to the daily
      physiological requirement should be recommended as the most reliable, effective
      and economical measure aimed to improve supply of the population with vitamins.

PMID- 7621955
TI  - [Oxygen diluents. Pro and contra].

PMID- 7621956
TI  - [The role of the calcium-accumulating capacity of the intracellular reserves in
      the smooth muscles of the blood vessels in the development of their catecholamine
      related damage].
AB  - Noradrenaline (10(-5)M) contractile reactions of smooth muscles of the rabbit
      arteries and veins (aorta, a. femoralis, V. cava posterior, v. femoralis) were
      investigated in the calcium-free medium using different methods of loading (0.5
      mM Ca2+; 0.5 mM Ca2+; 60 mM K+; 20 mM Ca2+) of their predepleted noradrenaline
      sensitive intracellular calcium stores. The comparative analysis of indices of
      relationships of maximum amplitudes using 0.5 mM Ca2+ in presence of 60 mM K+ and
      0.5 mM Ca2+, 20 mM Ca2+ and 0.5 mM Ca2+ has shown that calcium-accumulating
      ability of vein stores exceeds significantly that in arteries independent of the
      loading source. The toxic concentration of adrenaline (50 mg/kg in ear vein
      everyday during 5 days) inhibited more significantly the ability of arterial
      calcium stores to absorb cytoplasmic but not extracellular calcium. We failed to
      find the changes of the kind in veins. It has been found that the phenomena
      described are very important as they show different resistance of arteries and
      veins to the calcium injury.

PMID- 7621958
TI  - [The characteristics of individual reactions of the central hemodynamics to
      trauma].
AB  - Experiments with white mongrel male rats subjected to the standard trauma
      according to Kennon have revealed four types of responses of the central
      haemodynamics. The minimal mortality rate (31-38% for the first three days) was
      registered for hyper- and eudynamic types when the heart productivity parameters
      and atmospheric pressure either exceeded or were almost similar to those of
      intact animals. A decrease of these parameters (a hypodynamic type) has led to
      increase of the mortality rate (to 58%), but a sharp (more then 3 times) decrease
      of the cardiac index was characterized by a progressive increase of the arterial
      pressure and maximal mortality rate.

PMID- 7621959
TI  - [The mechanisms of allergic damage to the bronchoalveolar apparatus in poultry
      plant workers].
AB  - Specific and non-specific mechanisms of defense and damage were studied in 296
      poultry breeders, 20 of them were diagnosed the exogenic allergic alveolitis
      (EAA), the so-called "breeder's lung". The following characters were found: an
      increase in the blood leucocyte phagocytic activity, non-specific neutrophilic
      damage values, specific neutrophilic damage and specific lymphocyte damage
      values, lactate dehydrogenase activity, circulated immune complexes level,
      immunoglobulins A and M in blood serum in breeders with EAA. Only breeders with
      service of 1-5 and 11-15 years have shown no changes in non-specific neutrophilic
      damage values. A decrease in the T-lymphocyte content, theophylline-sensitive and
      theophylline-stable lymphocyte subpopulations in blood serum of breeders with EAA
      were observed as well.

PMID- 7621957
TI  - [An analysis of a disorder in the fibrin-forming phase in virtually healthy
      middle-aged and elderly subjects by using the ancistron test].
AB  - Damages in the fibrin-formation phase initiated by activation of the blood
      coagulation system and fibrinolysis and promoted by interaction between
      fibrinogen and its derivatives (dissolved fibrinogen, products of fibrin and
      fibrinogen lysis) and by the presence of various blood coagulation inhibitors
      were found in 34% of practically sound old people and in 47% of people of senile
      age. It is shown very significant to apply the "ancistrone time" test developed
      on the basis of enzyme ancistrone-H isolated from the venom of snake Agkistrodon
      halys halys for estimating the fibrin-formation phase both on the model system
      and in practically sound people of old and senile age. The ancistrone test
      permits rapidly (for 30-60s) obtaining qualitative and quantitative
      characteristic of the fibrinogen level in the blood plasma, of the products of
      fibrin and fibrinogen lysis, of the blood coagulation inhibitors.

PMID- 7621960
TI  - [The correction of disorders in arachidonic acid metabolism in coronary spasm of
      an immune origin].
AB  - The effect of phosphocreatine and hydroxamate-linoleate (an inhibitor of
      lipoxigenase) on development of the pathologic process in coronary vessels with
      immune (cytotoxic) injury of the heart was studied in the experiments on
      narcotized dogs. Development of the immune response after administration of
      cardiac serum resulted in development of large transmural damage of the left
      ventricle myocardium, increased resistance of coronary vessels and changed
      coronary vascular reactions, which correlates with changes in arachidonic acid
      metabolism. Experimental data described in this report demonstrate the efficiency
      of membrane coronary vessels stabilization and inhibition of a lipoxygenase
      pathway in arachidonic acid metabolism in protection of immune damage of the
      heart and coronary vessels.

PMID- 7621961
TI  - [The effect of mexidol on the rat periodontium during hypokinesia].
AB  - During 30-days-long hypokinesia changes in calcium-phosphoric metabolism,
      glycoprotein state, acid and alkaline phosphatase activity in bone tissue of the
      low jaw of rats proceed in some stages, that determines the nature of mexidol (3
      oxipyridine derivative) effects. The remedy demonstrated the most expressed
      protective effect on parodontal tissues on the 15th day of animals' mobility
      limitation. The data obtained show that mexidol effecting hypokinesia develop in
      some stages and depend on the initial state of the organism. They also reflect
      indirectly the significance of the antioxidant status of the organism in
      mineralization of the parodontal bone tissue.

PMID- 7621963
TI  - [The role of acetaldehyde in the pathogenetic mechanisms of the development of
      chronic alcoholism].
AB  - Experiments on white rats were carried out to confirm an important role of
      acetaldehyde in pathogeny of alcoholism. It is evidenced by results of
      experiments when animals were given acetaldehyde and medichronal (a drug which
      combines acetaldehyde) and by data obtained in the course of studies of changes
      in the content of endogenic ethanol and acetaldehyde, activity of alcohol
      dehydrogenase and aldehyde dehydrogenase, concentration of biogenic amines
      (catecholamines and serotonin) in the blood and brain structures.

PMID- 7621962
TI  - [The GABA-ergic system parameters of the adrenal cortex in animals with normal
      and stimulated steroidogenesis].
AB  - Activity of glutamate decarboxylase, a GABA synthesis enzyme, and intensity of
      its reception in the adrenal cortex and hypothalamus of guinea pigs and rats with
      normal and stimulated steroidogenesis was investigated. It has been shown that in
      the adrenal cortex there is a metabolic system which provides GABA synthesis from
      glutamate and mechanisms of GABA reception by plasmatic membranes. Mediator
      synthesis in the adrenal cortex is subjected to seasonal changes, GABA synthesis
      and reception selectively vary with administration of ACTH, prolactin and
      maintenance of animals on a diet with an excess of potassium ions.

PMID- 7621964
TI  - Interaction of avian sarcoma/leukemia viruses with heterologous hosts: inference
      for host-range and some pathogenic properties of human immunodeficiency viruses.
AB  - Although there are substantial differences between retroviruses originating from
      avian and primate species, a comparison of these two different biological systems
      reveals that interaction of these retroviruses with heterologous hosts involves
      similar biological principles. Retroviral isolates with high replicative capacity
      in natural targets (e.g. CD4+ lymphocytes and macrophages for human
      immunodeficiency viruses (HIVs) can infect other cell types [e.g. CD- astrocytes,
      follicular dendritic cells (FDC) in vivo and/or CD4+ neoplastic T cells in vitro]
      as well. These viral isolates may have a potential of infecting heterologous
      cells in vitro and can enlarge their host-range by establishing infection in
      other species, distantly related. Strains of avian sarcoma/leukemia viruses
      (ASLV) originating from their natural hosts, chickens, and infectious for other
      avian species, ducks, can frequently infect mammals (rodents). Similarly, HIV-1
      strains infectious for chimpanzees possess capacity of establishing chronic
      infection in pig-tailed macaques. The broad host-range of retroviral isolates in
      both viral systems is accompanied by presence of additional structures in viral
      envelope. These novel or additional envelope structures may recognize alternate
      viral receptor(s). Moreover, the enlarged host range of primary HIV-1 isolates is
      evaluated by infection of neoplastic CD4+ permanent cell line, MT2, and serves as
      a predictive marker of progression of the viral infection toward AIDS.

PMID- 7621965
TI  - Age-related changes in graft-versus-host reactivity of spleen cells from male,
      virgin, or multiparous female Long-Evans rats.
AB  - Spleen cell graft-versus-host (GVH) reactivity was determined in male and female,
      either virgin or breeder, Long-Evans (LE) rats from 3 to 24 months of age. The
      tests of a regional (popliteal lymph node enlargement index) and a systemic
      (splenomegaly index, mortality assay) GVH reaction was used. Although the GVH
      reactivity declined with age in both sexes, the onset of this decline was
      significantly delayed in 18-month-old virgin females in comparison with 12-month
      old males. Moreover, 6 or 7 consecutive pregnancies resulted in significantly
      enhanced GVH reactivity of 18-24-month-old females. This long-lasting effect of
      multiparity was observed in females mated either syngeneically or allogeneically.
      The possible role of neuroendocrine factors in delaying the age-related process
      of thymic involution in multiparous females is suggested.

PMID- 7621966
TI  - Role of IL-1 and TNF in the ribomunyl-induced radio-protection.
AB  - Ribomunyl, an immunomodulating agent, administered to mice 24 h before
      irradiation, has a radioprotective effect. Ribomunyl enhances renewal of the
      hematopoietic tissues damaged by radiation. The results of our work have
      confirmed that IL-1 and TNF play a significant role in an earlier recovery of
      hematopoiesis induced by Ribomunyl administration in sublethally irradiated mice.
      Anti-IL-1 administration before that of Ribomunyl significantly reduced the CFU
      GM increase in the bone marrow of mice on day 8 after irradiation with 6 Gy and
      prevented increase of the neutrophil granulocyte number in the peripheral blood.
      On the other hand, anti-TNF administration limited the CFU-S increase in the bone
      marrow and prevented a hematocrit increase in the peripheral blood.

PMID- 7621967
TI  - Evaluation of cadmium chloride cytotoxicity in Chinese hamster fibroblasts
      cultured in vitro.
AB  - Cytotoxicity of cadmium chloride was studied in fibroblast cell line V 79 (lung
      cells). Short-term (30 min) exposure of cells to cadmium chloride as well as 16-h
      exposure and long-term (continuous) treatment in the presence and absence of S9
      fraction were evaluated. Cell growth inhibition, measured as cell numbers in
      Petri dishes, was used as the endpoint of cytotoxicity and was given a graphic
      description of growth curves. Growth activity of cells was statistically analysed
      by multifactor analysis of variance. Statistically significant differences were
      found at choice concentrations (5 microM-50 microM cadmium chloride) for cell
      numbers by multiple range analysis between times of cell counting in the short
      term exposure trials, and in the continuous exposure trials between
      concentrations, times of counting cells, and absence and presence of S9 fraction.

PMID- 7621968
TI  - Age-dependent changes in proteoglycan biosynthesis in human intervertebral discs.
AB  - Proteoglycans from annulus fibrosus and nucleus pulposus of human intervertebral
      disc were investigated by electrophoresis in a composite agarose-polyacrylamide
      gel and immunohistochemically using various monoclonal antibodies against
      components of extracellular matrix. There were at least five different
      populations of proteoglycans in both annulus fibrosus and nucleus pulposus.
      Proteoglycans represented by individual electrophoretic bands differed from each
      other in hydrodynamic size but all of them contained epitopes present in keratan
      sulphate. Chondroitin sulphate could be detected in populations with molecular
      weight above 200,000 daltons. We could postulate that the cleavage of
      proteoglycan chains starts at the C-terminal end. This is supported by the
      finding that the globular region G2 on the protein core was detected in the same
      populations as keratan sulphate. We could confirm these results using tissue
      cultures of nucleus pulposus, inner and external part of annulus fibrosus. Of
      interest is the finding that there is de novo synthesis of globular domain G1
      only in structures of intervertebral disc from a 16-year-old male and not in the
      tissue of a 69-year-old male. This might contribute to an explanation of
      decreased aggregation of proteoglycans during the aging process.

PMID- 7621969
TI  - Dyslipidemia and diabetes: animal models.
AB  - Many models of diabetes dyslipidemia are available. Animals with chemically
      induced diabetes have been used to study insulin-dependent diabetes.
      Hypercholesterolemia in streptozotocin-induced diabetes in rats results from
      increased intestinal absorption and synthesis of cholesterol. Lipoproteins from
      diabetic rats are oxidized and demonstrate cytotoxicity, a feature which can be
      prevented by insulin or antioxidant treatment. Diabetic rabbits fed a cholesterol
      rich diet do not develop atherosclerotic lesions because accumulated VLDL are apo
      E-depleted, too large and do not enter into the arterial wall. Models for non
      insulin-dependent diabetes (NIDDM) are obtained through selective breeding or
      dietary conditions. The obese Zucker rat (fa/fa) is characterized by hyperphagy,
      hyperglycaemia, hyperinsulinemia, insulin-resistance, hypertriglyceridemia and
      hypercholesteolemia. It responds to dietary, hormonal and drug treatments, but
      does not develop atherosclerosis spontaneously. It is used as a model for
      obesity, NIDDM and type IV hyperlipidemia. The JCR:LA cp rat bears the corpulent
      gene and develops similar characteristics to those of the Zucker rat. However,
      insulin-resistance is more severe in homozygous males (cp/cp), and cardiovascular
      lesions are observed. Their appearance is reduced by treatments which decrease
      hyperinsulinemia and insulin resistance but not by lowering lipid levels alone.
      The sand rats (Psammomys obesus) develop obesity and NIDDM when fed a laboratory
      diet. When cholesterol and anti-thyroid drug are added to the diet, they develop
      cardiovascular lesions. This species constitutes a new model for studying
      atherosclerosis-related diabetes.

PMID- 7621970
TI  - [Post-prandial lipemia in diabetes. How? Why?].
AB  - Numerous studies show increasing evidences that a low post-prandial triglyceride
      metabolic capacity is likely to favour cardio-vascular disease, particularly
      coronary and cerebro-vascular atherosclerosis. Because of high fasting
      triglycerides, low HDL and high LDL3 lipid profile, abdominal obesity and insulin
      resistance, Type 2 diabetic patients are candidates to altered post-prandial
      lipemia. However many practical and methodological difficulties remain concerning
      the nature, lipid quantity and composition of the lipid load, the choice of
      accurate markers of liver derived lipoproteins, pointing out the urgent need for
      a standardization procedure.

PMID- 7621971
TI  - Postprandial lipoprotein clearance in type 2 diabetes: fenofibrate effects.
AB  - Lipoprotein abnormalities [mainly high levels of very-low-density lipoprotein
      triglycerides (TG) and low levels of high-density lipoprotein cholesterol]
      increase the risk of cardiovascular disease in Type 2 diabetic patients.
      Moreover, only fasting TG and central obesity appear to independently predict
      mortality from CAD in glucose-intolerant and diabetic subjects. It is noteworthy
      that fasting lipid levels in these patients are often relatively unaffected, and
      that plasma TG may remain < 2 g/l, the cutoff point currently considered to
      define moderate hypertriglyceridemia. Our study of postprandial lipaemia shows
      that lipid intolerance (a greater increase of postprandial TG and a slower return
      towards basal levels) was almost always present in these patients, enabling us to
      detect atherogenic changes in plasma lipoproteins. Preliminary results indicate
      that fenofibrate treatment in Type 2 diabetes under optimised metabolic control
      improves not only fasting lipid levels but also postprandial lipaemia and
      associated abnormalities in lipoprotein levels and composition.

PMID- 7621972
TI  - Lipolysis-stimulated receptor: a newcomer on the lipoprotein research scene.
AB  - It has been widely accepted that the remnants of the intestinally-derived
      lipoprotein chylomicrons, i.e., chylomicron remnants (CMR), are cleared from the
      circulation by a receptor genetically distinct from the well-known LDL-receptor.
      This second receptor was initially considered as a receptor specific for apo E,
      in contrast to the LDL-receptor, which binds both apo B and apoE. This article
      critically examines the current dogma of the putative CMR receptor, as well as
      both supporting and conflicting evidence for the recently-proposed identity of
      this receptor with the LDL-receptor related protein (LRP). Next, we introduce the
      lipolysis-stimulated receptor, LSR, which bears all the biochemical
      characteristics of the CMR receptor. In addition, the apparent number of LSR
      expressed in the liver is inversely correlated with nonfasting levels of plasma
      triglycerides. A change in LSR expression and parallel inverse change in plasma
      triglycerides is observed in rats treated with hyperlipidemic (retinoic acid) or
      hypolipidemic (fish oil in MaxEPA) agents, indicating that LSR represents a
      definite target for pharmacological management of hyperlipidemia. In support of
      this notion is the observation that MaxEPA, which causes an increase in LSR
      expression, also reduces both plasma triglyceride and cholesterol levels in the
      thus far intractable homozygous Watanabe heritable hyperlipidemic rabbit.

PMID- 7621973
TI  - [Lipoprotein (a) and diabetes mellitus].
AB  - Lp(a) has atherogenic and thrombotic properties and is considered to be a major
      risk factor for the development of atherosclerotic disease. The risk of
      cardiovascular disease is increased in both insulin-dependent (IDDM) and non
      insulin-dependent diabetes mellitus (NIDDM), and Lp(a) has attracted attention as
      a potential risk factor in diabetic patients. Lp(a) levels are "probably"
      elevated in IDDM patients and related to altered metabolic control and increased
      urinary albumin excretion rate or renal insufficiency, although results are
      controversial. There appears to be a real difference between the Lp(a) of
      patients with proliferative diabetic retinopathy and those with or without
      background retinopathy. The plasma Lp(a) level may therefore be associated with
      microangiopathy in some IDDM patients. However, data relating Lp(a) to
      complications of diabetes are limited, and the literature is conflicting. The few
      available data suggest that Lp(a) is not elevated in NIDDM patients and that
      there is no strong link between blood glucose control and plasma Lp(a). There is
      no clear evidence as to whether Lp(a) is related to microalbuminuria in NIDDM
      patients. There is little evidence for a correlation between increased risk of
      cardiovascular disease and plasma Lp(a) among diabetic patients. However, some
      diabetic patients with coronary heart disease have elevated plasma Lp(a), which
      seems to be correlated with genetic factors (especially the isoforms of
      apolipoprotein a) rather than to diabetes per se. Lp(a) synthesis and catabolism
      could be influenced by insulin or by diabetes and its metabolic concomitants. The
      atherogenic and thrombogenic potential of Lp(a) could also be increased in
      diabetic patients. Plasma Lp(a) should be measured for both IDDM and NIDDM
      patients. If the Lp(a) level is elevated, it seems reasonable to check the other
      major vascular risk factors.

PMID- 7621974
TI  - Prospects for drug therapy for hyperlipoproteinaemia.
AB  - Prospects for therapy for hyperlipoproteinaemia are likely to rely more heavily
      on improvement of known molecules than on development of new ones aimed at
      various components of the plasma lipid transport system. Promising advances are
      revealed in both directions. A new synthetic inhibitor of HMG CoA reductase,
      atorvastatin, lowers plasma low-density lipoprotein (LDL)-cholesterol and
      triglycerides and increases high-density lipoprotein (HDL)-cholesterol with
      greater potency than currently available drugs of this class. A highly selective
      thyromimetic, CGS 26214, virtually devoid of cardiovascular effects, has potent
      cholesterol-lowering activity in several models, reduces post-prandial response
      to a fat load in rats and markedly lowers Lp(a) concentrations in monkeys. There
      is a trend to develop inhibitors of acyl CoA: cholesterol acyltransferase (ACAT)
      with more than one desirable activity. Thus, ACA-147, which inhibits cholesterol
      absorption, reduces LDL, prevents their oxidation and increases HDL-cholesterol,
      was antiatherogenic in cholesterol-fed rabbits. Sch48461 has emerged as an
      inhibitor of cholesterol absorption by an as yet unknown mechanism unrelated to
      ACAT inhibition, while a synthetic saponin, CP- 148,623, which prevents the entry
      of cholesterol into intestinal mucosa, has a potential for combination therapy.
      Approaches which may find applications in a more distant future include molecular
      cages to trap cholesterol selectively, "cholesterol vaccination", overexpression
      of the apolipoprotein E gene in the skin, and gene therapy. With improvements in
      understanding of the pathophysiology of dyslipoproteinaemias, drug discovery and
      development may focus more in future on the specific causes of disease.

PMID- 7621975
TI  - Lipoproteins and diabetes. Symposium proceedings. Paris, France, 2 December 1994.

PMID- 7621976
TI  - [Role of free fatty acids in the insulin resistance of non-insulin-dependent
      diabetes].
AB  - Non-insulin-dependent diabetes (NIDDM) is characterized by overproduction of
      glucose, decreased effects of insulin on glucose utilization and production, and
      a defect in glucose-induced insulin secretion. NIDDM is also associated with
      defects in fatty acid metabolism, i.e. enhanced lipolysis and impaired
      suppression of adipose tissue lipolysis in response to insulin, and increased
      plasma free fatty acid levels. It has been suggested that the "glucose-fatty acid
      cycle" is enhanced in NIDDM and could contribute to disturbed glucose
      homeostasis. Although the use of intralipid + heparin infusion and inhibitors of
      lipolysis or fatty acid oxidation indicates that the glucose-fatty acid cycle
      exists both in normal and NIDDM subjects, it does not seem to be the primary
      cause of distributed glucose homeostasis in lean NIDDM subjects or their first
      degree relatives. However, the glucose-fatty acid cycle could contribute to
      overproduction of glucose (by stimulating gluconeogenesis) and muscle insulin
      resistance in obese NIDDM subjects. Studies performed in the rat suggest that
      impaired glucose-induced insulin secretion could also be related to chronic
      exposure of pancreatic beta cells to elevated plasma free fatty acid levels. The
      role of the glucose-fatty acid cycle in normal subject must be clarified, and its
      contribution to decreased glucose-induced insulin secretion in NIDDM requires
      further investigation.

PMID- 7621977
TI  - Lipoprotein glyco-oxidation.
AB  - Cardiovascular diseases are the leading cause of death during diabetes, and
      qualitative changes in lipoproteins play a role in the pathogenesis of
      atherosclerosis. Hyperglycaemia induces glycation of lipoproteins, particularly
      low-density lipoproteins (LDL), preventing the recognition of apoprotein B by the
      specific receptor and favouring the accumulation of LDL in macrophages and their
      oxidation. Other effects contribute to increased LDL oxidation in diabetes:
      higher production (and decreased degradation) of free radicals, the association
      of hypertriglyceridemia with the presence of small, dense, more easily oxidizable
      LDL, and high-density lipoprotein anomalies which reduce LDL antioxidant
      capacities. Glycation- oxidation interactions are complex. Although glycated LDL
      are more easily oxidizable, antioxidants could also reduce protein glycation
      independently of glycaemic balance. The role of glyco-oxidative changes in the
      pathogenesis of atherosclerosis during diabetes is difficult to determine, partly
      because of methodological problems related to the presence of circulating
      antioxidants which allow only minimal (and not easily demonstrable) LDL
      oxidation. The development of measurements sensitive to lipoprotein oxidation
      should facilitate the determination of LDL oxidative status. The main means of
      preventing and treating glyco-oxidative alterations are the normalisation of LDL
      cholesterol concentrations and the improvement of glycaemic balance. Prospective
      studies are needed to determine the role of antioxidants in the prevention and/or
      treatment of atheromatous disease during diabetes.

PMID- 7621978
TI  - Non-enzymatic glycosylation of apolipoprotein A-I and its functional
      consequences.
AB  - High-density lipoproteins (HDL) are believed to protect against atherosclerosis
      by promoting the process of reverse cholesterol transport. This process involves
      different steps including efflux of cellular cholesterol, cholesterol
      esterification and lipid transport and exchange. Apolipoprotein (apo) A-I, the
      major HDL apolipoprotein, and the HDL-associated enzyme lecithin-cholesterol
      acyltransferase (LCAT), which uses apo A-I as a cofactor, play a crucial role in
      reverse cholesterol transport. HDL may be classified into species according to
      their apolipoprotein content. Recent data concerning HDL particles indicate that
      lipoproteins containing apo A-I but not apo A-II (LpA-I) are more effective
      carriers of free cholesterol and are associated with a protective effect against
      coronary heart disease. In vitro studies have shown that glycosylated HDL are
      functionally abnormal and may be considered atherogenic. Our study considers the
      different impacts of non-enzymatic glycosylation of apo A-I or protein-HDL on the
      reverse cholesterol transport process.

PMID- 7621979
TI  - Apolipoprotein A-IV in diabetes mellitus.
AB  - Apolipoprotein A-IV is considered to play a role in triglyceride-rich lipoprotein
      metabolism, in reverse cholesterol transport, and in facilitation of CETP
      (Cholesterolyl Ester Transfer Protein) activity. Moreover, apoA-IV is genetically
      polymorphic in humans, in whom two major isoproteins (apoA-IV 1 and apoA-IV 2)
      are present and have differences that influence the apoA-IV phenotype in lipid
      metabolism. In non-insulin-dependent-diabetes, increased apoA-IV levels are
      found, mainly related to hypertriglyceridemia and to a lesser extent to HDL
      cholesterol level; apoA-IV phenotype distribution is not different from controls;
      in the control population, the potential protective lipid profile (characterized
      by increased HDL and HDL2 cholesterol levels) related to the apoA-IV 1-2
      phenotype, is no longer found in NIDDM patients (the metabolic state of NIDDM
      appears to have effected the potential protective lipid profile related to the
      apoA-IV 1-2 phenotype); and plasma apoA-IV levels is associated with increased
      prevalence for macrovascular disease. In non-insulin-dependent diabetes treated
      with insulin, apoA-IV levels are increased. Unlike results for NIDDM patients
      undergoing oral treatment, the increase in apoA-IV level is not related to
      hypetriglyceridemia, so that the effect on lipid metabolism may be different.

PMID- 7621980
TI  - Influence of immune signals on the hypothalamic-pituitary axis of the rodent.
AB  - The immune system and the hypothalamic-pituitary (H-P) axis are functionally
      connected, so that exposure to antigens elicits a coordinated response which
      allows the organism to successfully withstand immunologic challenges. An
      important feature of this bilateral communication is the appearance of proteins
      released into the circulation by activated immune cells. These proteins, called
      cytokines or interleukins, stimulate the activity of the H-P axis, thus
      increasing circulating ACTH and corticosteroid levels. This in turn induces
      metabolic changes such as increases in energy substrates, restrains the activity
      of specific immune cells, and alters the release of secretagogues important for
      both the immune system and neuroendocrine organs. After acute increases in blood
      borne levels of cytokines, nerve terminals in the median eminence, particularly
      those containing corticotropin-releasing factor (CRF), represent an important
      site of action of these immune signals. Subsequently, changes take place within
      the brain in general and the hypothalamus in particular. They include the
      synthesis/release of peptides such as CRF and vasopressin, of neurotransmitters
      such as catecholamines and prostaglandins, and of cytokines themselves. Upon
      prolonged exposure to blood-borne immune signals additional mechanisms come into
      play, including those taking place directly at the pituitary level. These
      observations indicate that cytokines released into the general circulation act on
      multiple sites within the H-P axis, a phenomenon that relies on the recruitment
      of a large number of pathways. This review discusses these pathways and the
      mechanisms through which they allow cytokines to convey the occurrence of immune
      activation to the brain.

PMID- 7621981
TI  - The self-priming effect of LHRH: a unique servomechanism and possible cellular
      model for memory.

PMID- 7621982
TI  - Stress-induced norepinephrine release in the hypothalamic paraventricular nucleus
      and pituitary-adrenocortical and sympathoadrenal activity: in vivo microdialysis
      studies.
AB  - The hypothalamic-pituitary-adrenocortical (HPA) axis and the autonomic nervous
      system are major effector systems that serve to maintain homeostasis during
      exposure to stressors. In the past decade, interest in neurochemical regulation
      and in pathways controlling activation of the HPA axis has focused on
      catecholamines, which are present in high concentrations in specific brain areas-
      especially in the hypothalamus. The work described in this review has
      concentrated on the application of in vivo microdialysis in rat brain regions
      such as the paraventricular nucleus (PVN) of the hypothalamus, the central
      nucleus of the amygdala (ACE), the bed nucleus of the stria terminalis (BNST),
      and the posterolateral hypothalamus in order to examine aspects of
      catecholaminergic function and relationships between altered catecholaminergic
      function and the HPA axis and sympathoadrenal system activation in stress.
      Exposure of animals to immobilization (IMMO) markedly and rapidly increases rates
      of synthesis, release, and metabolism of norepinephrine (NE) in all the brain
      areas mentioned above and supports previous suggestions that in the PVN NE
      stimulates release of corticotropin-releasing hormone (CRH). The role of NE in
      the ACE and the BNST and most other areas possessing noradrenergic innervation
      remains unclear. Studies involving lower brainstem hemisections show that
      noradrenergic terminals in the PVN are derived mainly from medullary
      catecholaminergic groups rather than from the locus ceruleus, which is the main
      source of NE in the brain. Moreover, the medullary catecholaminergic groups
      contribute substantially to IMMO-induced noradrenergic activation in the PVN.
      Data obtained from adrenalectomized rats, with or without glucocorticoid
      replacement, and from hypercortisolemic rats suggest that glucocorticoids
      feedback to inhibit CRH release in the PVN, via attenuation of noradrenergic
      activation. Results from rats exposed to different stressors have indicated
      substantial differences among stressors in eliciting PVN noradrenergic responses
      as well as of responses of the HPA, sympathoneural, and adrenomedullary systems.
      Finally, involvement of other areas that participate in the regulation of the HPA
      axis such as the ACE, the BNST, and the hippocampus and the importance of stress
      induced changes in expression of immediate early genes such as c-fos are
      discussed.

PMID- 7621983
TI  - Total cortisol, free cortisol, and growth hormone associated with brief social
      separation experiences in young macaques.
AB  - Many behavioral, immunological, and physiological consequences or brief maternal
      separation in bonnet (Macaca radiata) and pigtail monkeys (Macaca nemistrina)
      have been documented. However, the impact of social separation on plasma cortisol
      and growth hormone is unknown for these particular species. In the present study,
      the behavioral and endocrinological consequences of a 2-week maternal separation
      in socially housed infant bonnet and pigtail monkeys were followed. In seven
      pairs (separated and matched control) of bonnet and six pairs of pigtail infants,
      plasma was obtained under baseline, separated, and reunion conditions twice
      weekly for the duration of the study. Blood samples were obtained from both
      infants of the pair in approximately 10 min. Plasma total cortisol, free
      cortisol, and growth hormone were measured in these samples. Focal animal
      behavioral observations were made on all subjects twice daily throughout the
      study period. In both species, total cortisol and free cortisol rose immediately
      following maternal separation in comparison to the matched nonseparated controls
      and returned to basal levels (e.g., that of matched nonseparated controls)
      following reunion with the mother. In contrast, plasma growth hormone rose only
      in the pigtail infants over a time course that peaked around the time of reunion.
      Multiple regression techniques indicated for the first week of separation, in the
      separated but not control subjects, that mean plasma free and total cortisol was
      positively related to distress behaviors (vocalization and postural slouch)
      observed during this week and negatively related to social behaviors (play and
      proximity to others) noted during the same period. In contrast, plasma growth
      hormone was related to both species and sex of the subjects but unrelated to
      behavioral variables.

PMID- 7621985
TI  - Delayed development of conditioned heart rate responses to auditory stimuli in
      the rat.
AB  - This study examined heart rate responses to an auditory conditioned stimulus
      during development in the rat. The unconditioned stimulus (US) in all experiments
      was an acoustic startle stimulus. The conditioned stimulus elicited a monophasic
      bradycardia in animals 21 days of age and older, but no response in younger
      animals. These results are strikingly similar to an earlier study that used shock
      as the US (Campbell & Ampuero, 1985). Further, the conditioned cardiac response
      in adults was found to be mediated entirely through activation of the
      parasympathetic division of the autonomic nervous system (ANS) even though the US
      unconditionally activates the sympathetic system at that age. The delayed
      development of several different forms of conditioned fear is discussed.

PMID- 7621986
TI  - The influence of flavor and color on drink identification by children and adults.
AB  - This study investigated how color and flavor influences drink identification by
      children and adults. The children ranged in age from 2 to 18 years of age. Each
      subject tasted four drinks that differed in color and flavor. Each drink had an
      atypical color-flavor pairing (e.g., brown-pineapple) or a typical pairing (e.g.,
      brown-chocolate). After tasting each drink, the subject chose which of four
      flavor names identified the drink. For the atypical drinks, the selection of
      color-associated names (e.g., chocolate for a brown drink) decreased, and the
      selection of flavor-associated names increased with age from the preschoolers to
      the adults. For the typical drinks, the selection of the correct name was greater
      than 80% for all ages. These results suggest that drink identification becomes
      more influenced by flavor as children get older because of an increase in the
      ability of children to focus on flavor as their perceptual-attentional skills
      mature.

PMID- 7621984
TI  - Dissociation of behavioral and neural correlates of early associative learning.
AB  - Wistar rat pups were trained in an olfactory associative conditioning task on
      postnatal Day 6, 12, or 20. The training consisted of 20 pairings of a novel odor
      (peppermint) with footshock (1.5 mA, 1 s) with an intertrial interval of 3 min.
      Additional pups were trained in either unpaired or naive control conditions. On
      the day following training, pups were either tested for their behavioral response
      to the conditioned odor in a two-odor choice test, or injected with 14C-2
      deoxyglucose and exposed to the odor for examination of olfactory bulb neural
      responses to the odor. The results demonstrate that, although pups at all ages
      learned to avoid the odor, only pups trained during the first postnatal week had
      a modified olfactory-bulb glomerular-layer response to the odor. These results
      suggest that although olfactory memory is correlated with modification of
      olfactory bulb glomerular layer function in newborns, these changes are not
      required for normal memory in older pups.

PMID- 7621987
TI  - Development of water-immersion produced analgesia.
AB  - Nociceptive and antinociceptive systems change dramatically during the first 10
      days of life in rats. The present studies sought to determine whether exposure to
      water stress can produce analgesia during this period, and when in the ontogeny
      changes in magnitude and duration of such stress-induced analgesia occur. It was
      found that exposure to water reliably induced analgesia as early as 3 days
      postnatally. This analgesia increased in magnitude and duration at the age of 17
      20 days, when supra-spinal descending inhibition develops, and depended on the
      temperature of the water and duration of exposure.

PMID- 7621988
TI  - The insulin gene promoter. A simplified nomenclature.

PMID- 7621989
TI  - Lipotoxicity in the pathogenesis of obesity-dependent NIDDM. Genetic and clinical
      implications.
AB  - We review evidence that increased tissue levels of fatty acyl CoA cause the beta
      cell abnormalities of nondiabetic obesity and ultimately result in obesity
      dependent diabetes. Nondiabetic obesity in Zucker rats is characterized by
      hypersecretion of insulin at normal fasting and subfasting glucose
      concentrations. This is a result of beta-cell hyperplasia and increased low Km
      glucose usage and oxidation. These abnormalities, the hyperinsulinemia, the
      hyperplasia of beta-cells, i.e., its in vitro equivalent, enhanced
      bromodeoxyuridine incorporation, and the increased low Km glucose usage can be
      induced by culturing normal islets with 2 mmol/l free fatty acids (FFAs). Once
      obese Zucker diabetic fatty rats become diabetic, glucose-stimulated insulin
      secretion (GSIS) is absent and beta-cell GLUT2 reduced. Islet triglyceride (TG)
      content is increased 10-fold, probably reflecting increased FFA delivery (plasma
      FFA levels > 1.5 mmol/l) beginning about 2 weeks before the onset of diabetes.
      These beta-cell abnormalities, GSIS loss, GLUT2 loss, and TG accumulation, are
      prevented by reducing plasma FFAs by caloric restriction and by nicotinamide
      injection. The loss of GSIS and the accumulation of TGs, but not the GLUT2 loss,
      can be induced in vitro in normal islets cultured in a 2 mmol/l FFA-containing
      medium, but prediabetic islets seem far more vulnerable to FFA-induced functional
      impairment and TG accumulation. It is proposed that in uncomplicated obesity,
      increased lipid availability (FFA levels < 1.5 mmol/l) induces both
      hyperinsulinemia and insulin resistance in parallel fashion, thereby maintaining
      normoglycemia.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7621990
TI  - Intrathymic transplantation of islet antigen affects CD8+ diabetogenic T-cells
      resulting in tolerance to autoimmune IDDM.
AB  - The acquisition of T-cell tolerance in the thymus is limited to those antigens
      expressed in the thymus at the time of T-cell development. Normally, islet
      antigens that are involved in insulin-dependent diabetes mellitus (IDDM) are not
      present in the thymus, but we have previously shown that transplantation of
      islets expressing relevant antigens into the thymus at the time of T-cell
      maturation results in prevention of IDDM in the multidose streptozotocin model of
      diabetes mellitus (MDSDM). Although both CD4+ and CD8+ T-cells are involved in
      the pathogenesis of this disease, the cells affected by intrathymic
      transplantation of islets are unknown. In this study, we have identified which T
      cell subsets are affected by intrathymic islet antigens. Streptozotocin (STZ)
      treated syngeneic islets were transplanted into the thymuses of C57BL/KsJ mice,
      and CD4+, CD8+, or both subsets of cells were transiently depleted with
      monoclonal antibodies (mAbs). After T-cell repopulation, animals that had
      received intrathymic islets followed by anti-CD8 mAb (P < 0.05) or both anti-CD4
      and anti-CD8 mAbs (P < 0.01) but not anti-CD4 mAb alone were resistant to the
      development of autoimmune diabetes after five low doses of STZ. Insulitis was
      also reduced in mice receiving intrathymic islets and anti-CD8 (P < 0.025) or
      both anti-CD4 and anti-CD8 mAbs (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7621991
TI  - Involvement of ATP-sensitive K+ channels in free radical-mediated inhibition of
      insulin secretion in rat pancreatic beta-cells.
AB  - To explore the mechanisms of inhibition of insulin secretion in pancreatic beta
      cells by oxygen free radicals, we studied the effects of H2O2 on membrane
      currents using the patch-clamp technique. Exposure of beta-cells to H2O2 (> or =
      30 mumol/l) increased the activity of ATP-sensitive potassium (K+ATP) channels
      without changing the single channel conductance in cell-attached membrane
      patches. Action currents observed during superfusion of 11.1 mmol/l glucose were
      suppressed. In inside-out membrane patches, the activity of K+ATP channels was
      not influenced by H2O2. In conventional whole-cell clamp experiments using a
      pipette solution containing 3 mmol/l ATP, H2O2 did not influence the membrane
      currents. However, H2O2 did activate the K+ATP channel current in perforated
      whole-cell clamp configurations. The increased K+ATP channel current was reversed
      by subsequent exposure to 11.1 mmol/l 2-ketoisocaproic acid. In cell-attached
      membrane patches, the K+ATP channel current evoked by exposure to 30 mumol/l H2O2
      was inhibited by exposure to 11.1 mmol/l glyceraldehyde, whereas the channel was
      again activated by exposure to 0.3 mmol/l H2O2. Subsequent superfusion of 11.1
      mmol/l 2-ketoisocaproic acid inhibited the channel; this effect was counteracted
      by exposure to 10 mmol/l H2O2. Transient inhibition of K+ATP channels with
      provocation of action potentials was observed after washout of 100 mumol/l H2O2
      during superfusion of 2.8 or 11.1 mmol/l glucose.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7621993
TI  - Effect of a specific endothelin receptor A antagonist on mRNA levels for
      extracellular matrix components and growth factors in diabetic glomeruli.
AB  - We have previously reported that the mRNA levels of extracellular matrix (ECM)
      components including alpha 1(I), alpha 1(III), and alpha 1(IV) collagen chains,
      laminin B1 and B2 chains, and growth factors including tumor necrosis factor
      (TNF)-alpha, platelet-derived growth factor (PDGF)-B chain, transforming growth
      factor (TGF)-beta, and basic fibroblast growth factor (FGF) all increase with age
      in diabetic glomeruli. The present study was designed to assess whether
      glomerular expression of these mRNAs in rat diabetic glomeruli is affected by a
      specific endothelin receptor A antagonist, FR139317. Diabetes was produced by
      streptozotocin injection, and animals were divided into four groups: untreated
      diabetic rats, FR139317-treated diabetic rats, control nondiabetic rats, and
      FR139317-treated control rats. FR139317 treatment was continued for 24 weeks.
      FR139317 attenuated the rise in creatinine clearance (P < 0.01) and reduced
      urinary protein excretion (P < 0.01) in diabetic rats, but did not affect blood
      pressure. FR139317 attenuated the increases in glomerular mRNA levels of alpha
      1(I) (P < 0.01), alpha 1(III) (P < 0.01), and alpha 1(IV) (P < 0.01) collagen
      chains, laminin B1 (P < 0.01) and B2 (P < 0.01) chains, TNF-alpha (P < 0.01),
      PDGF-B (P < 0.01), TGF-beta (P < 0.001) and basic FGF (P < 0.01) in diabetic
      rats. However, FR139317 did not affect these mRNA levels in glomeruli of control
      rats. These findings suggest that FR139317 may be useful in the treatment of
      diabetic glomerulopathy by reducing mRNA levels of ECM components and growth
      factors.

PMID- 7621992
TI  - Peroxidative stress in diabetic blood vessels. Reversal by pancreatic islet
      transplantation.
AB  - Diabetic complications are believed to arise, in part, through an increase in
      oxidative stress. We characterized antioxidant status in vascular tissue in
      untreated diabetic rats and in diabetic rats rendered euglycemic by pancreatic
      islet transplantation. Three key endogenous antioxidant enzymes (e.g., superoxide
      dismutase, catalase, and glutathione peroxidase) were measured. Sprague-Dawley
      rats with streptozotocin-induced diabetes were killed after 8 weeks of untreated
      hyperglycemia and compared with age-matched controls. Eight weeks of untreated
      diabetes resulted in a significant increase of tissue catalase in aorta, iliac
      artery, and femoral artery as compared with controls. No significant changes in
      either superoxide dismutase or glutathione peroxidase were observed in aorta,
      iliac artery, or femoral artery of diabetic animals. This increase in catalase in
      diabetic vascular tissue suggests increased oxidative stress due to chronic
      exposure to H2O2 in vivo. To assess the impact of islet transplantation on
      oxidative stress in vascular tissue, inbred Lewis strain rats were rendered
      diabetic with streptozotocin. After 8 weeks of untreated diabetes, rats received
      an intraportal islet isograft and were monitored for 4 subsequent weeks of
      euglycemia. Islet transplantation improved weight gain and normalized blood
      glucose and total glycosylated hemoglobin. While catalase was significantly
      increased in aorta and iliac artery at 8 and 12 weeks of diabetes, vascular
      catalase was restored to normal by islet transplantation. These data suggest that
      islet transplantation is an effective treatment strategy to minimize increased
      oxidative stress in diabetic vasculature.

PMID- 7621994
TI  - Brainstem dysfunction is provoked by a less pronounced hypoglycemic stimulus in
      diabetic BB rats.
AB  - Recent studies suggest that moderate hypoglycemia impairs brainstem function in
      normal humans and rats. To examine whether diabetes alters this response,
      simultaneous auditory-evoked potentials were recorded directly from the inferior
      colliculus (IC) and from the brainstem before and after controlled hypoglycemia
      (clamp) in awake insulin-dependent diabetic BB/Wor rats. Hyperglycemic diabetic
      animals were studied either during hyperinsulinemic euglycemia (5.6 mmol/l, n =
      4) or mild hypoglycemia (3.5 mmol/l, n = 9). Nondiabetic controls were also
      studied at 3.5 mmol/l (n = 7) and at 2.8 mmol/l (n = 6). Brainstem function was
      not affected during euglycemia in diabetic rats. However, when plasma glucose was
      lowered to 3.5 mmol/l, the diabetic rats showed a 10% delay in IC evoked
      potential (ICEP) latency, whereas nondiabetic animals did not. This occurred
      despite similar counterregulatory hormones in both groups. The brainstem auditory
      evoked potential (BAEP) localized the defect in the diabetic group to an area in
      or near the IC. When glucose levels were lowered to 2.8 mmol/l, however, brain
      function was impaired in nondiabetic rats as well. Again the defect was
      restricted to an area in or near the IC. We conclude that mild hypoglycemia
      causes a functional impairment in the IC region of the brainstem in both
      nondiabetic and diabetic rats. However, in the diabetic rats, this alteration
      occurs after a less pronounced hypoglycemic stimulus. Our findings suggest that
      chronic hyperglycemia leads to metabolic adaptions that render the diabetic brain
      more susceptible to mild hypoglycemia.

PMID- 7621995
TI  - Comparative study of the protective effect afforded by intravenous administration
      of bovine or ovine insulin to young NOD mice.
AB  - Soluble bovine or ovine insulin given intravenously to female NOD mice shortly
      after weaning had a downregulating effect on several autoimmune parameters
      associated with insulin-dependent diabetes. The titer of spontaneous anti-insulin
      antibodies was reduced, insulitis was delayed and less severe, and only 25% of
      treated mice were diabetic at 30 weeks compared with 70% of untreated mice. An
      interesting paradox occurred in that bovine insulin, although poorly immunogenic
      in NOD mice and ineffective as a tolerogen for complete Freund's adjuvant-induced
      cellular and humoral responses to ovine insulin, was nearly as effective as
      immunogenic ovine insulin in protecting against diabetes and better than ovine
      insulin at downregulating spontaneous autoantibodies to insulin. Bovine and ovine
      insulins differ by only one amino acid on the A-chain loop, but whereas
      modulation of the induced response to ovine insulin appeared to be sheep
      specific, modulation of the induced and spontaneous autoimmunity was achieved
      almost equally well by bovine or ovine insulin. We suggest therefore that
      modulation of the induced and spontaneous responses are dependent on different T
      cell epitopes and that modulation of spontaneous autoimmunity appears to be
      governed by an epitope common to both insulins.

PMID- 7621996
TI  - Excessive secretion of insulin precursors characterizes and predicts gestational
      diabetes.
AB  - Using assays that specifically measure insulin, intact proinsulin, and 32,33
      split proinsulin, we examined the beta-cell secretory response to an oral glucose
      tolerance test (OGTT) in 64 women with gestational diabetes mellitus (GDM) and
      154 pregnant normoglycemic control subjects of comparable age and body mass
      index. Women with GDM were characterized by a lower 30-min insulin increment
      (40.8 [34.9-47.6] vs. 58.6 [53.6-64] pmol insulin/mmol glucose, P < 0.001;
      geometric mean [95% confidence interval]) and a higher plasma insulin level at
      120 min (702 [610-808] vs. 444 [400-492] pmol/l, P < 0.001). 32,33 split
      proinsulin levels were elevated in GDM patients in both fasting (9.1 [7.3-11.4]
      vs. 6.7 [6.0-7.5] pmol/l, P < 0.02) and 120-min (75.2 [62.9-90.0] vs. 52.2 [46.7
      58.3] pmol/l, P < 0.001) samples, respectively. Intact proinsulin levels were
      significantly elevated at 120 min in the women with GDM (21.3 [18.1-25.1] vs.
      14.8 [13.4-16.3] pmol/l, P < 0.001). Thus, the qualitative abnormalities of
      insulin secretion in GDM patients (low 30-min insulin increment, high 120-min
      plasma insulin, and elevated 32,33 split proinsulin) are similar to those seen in
      nonpregnant subjects with impaired glucose tolerance. To determine whether
      measures of proinsulin-like molecules (PLMs) might assist in the prediction of
      GDM, women who had a 1-h glucose level of > 7.7 mmol/l after a 50-g glucose
      challenge at 28-32 weeks' gestation had insulin and PLMs measured in the 1-h
      sample.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7621997
TI  - Ten-year incidence of gross proteinuria in people with diabetes.
AB  - There are few population-based epidemiological data describing the long-term
      incidence of gross proteinuria in people with diabetes. We performed a population
      based study in southern Wisconsin of individuals with diabetes diagnosed at
      either < 30 years of age and taking insulin (younger-onset, n = 666) or > or = 30
      years of age either taking (older-onset taking insulin, n = 376) or not taking
      insulin (older-onset not taking insulin, n = 418). The presence of gross
      proteinuria (> or = 0.3 g/l) was determined by means of a reagent strip. The
      incidence of proteinuria in the 10-year interval was 28% in the younger-onset
      group, it was 40% in the older-onset group taking insulin, and it was 33% in the
      older-onset group not taking insulin. After we controlled for other risk factors,
      the 10-year incidence of proteinuria was significantly related to higher
      glycosylated hemoglobin level and diastolic blood pressure at baseline and to an
      increase in glycosylated hemoglobin level and an increase in diastolic blood
      pressure from baseline to the 4-year follow-up in the younger-onset group and to
      higher glycosylated hemoglobin level, higher systolic blood pressure, and higher
      total pack-years of cigarettes smoked at baseline and an increase in systolic
      blood pressure from baseline to the 4-year follow-up in the older-onset groups.
      These data suggest that modification of three factors--hyperglycemia, high blood
      pressure, and smoking--may lead to a reduction in the long-term incidence of
      proteinuria.

PMID- 7621998
TI  - Hyperglycemia-induced thrombin formation in diabetes. The possible role of
      oxidative stress.
AB  - Diabetes is characterized by the existence of a thrombosis-prone condition,
      possibly related to hyperglycemia. However, the mechanism linking hyperglycemia
      to the activation of the coagulation cascade is still unclear. It has been
      recently suggested that diabetes is accompanied by increased oxidative stress. In
      this work, the possibility that oxidative stress may be involved in the
      hyperglycemia-induced coagulation activation has been evaluated. Prothrombin
      fragment 1 + 2 (F1 + 2), which represents a reliable marker of the amount of
      thrombin released in the circulation, has been chosen for studying thrombin
      formation in vivo. In nine type II diabetic patients and in seven healthy control
      subjects, matched for age and body mass index, three different experiments were
      performed: oral glucose tolerance test (OGTT), intravenous antioxidant
      glutathione (GSH) administration for 2 h, and OGTT plus intravenous GSH
      administration. Samples were drawn at -15 min and every 30 min from 0 to 180 min.
      During the OGTT, F1 + 2 significantly increased in both diabetic and healthy
      subjects. GSH administration during OGTT normalized this phenomenon. GSH
      administration alone significantly decreased F1 + 2 in diabetic patients, while
      no effect was observed in the normal subjects. These data suggest that
      hyperglycemia may induce thrombin activation, possibly inducing an oxidative
      stress, and that antioxidant GSH may counterbalance this effect.

PMID- 7621999
TI  - Decreased degradative enzymes in mesangial cells cultured in high glucose media.
AB  - Abnormalities in extracellular matrix degradation may play a pathogenetic role in
      diabetic nephropathy. Cultured renal mesangial cells are known to synthesize
      increased amounts of matrix proteins when incubated in high glucose media (e.g.,
      30 mmol/l). However, the effect of glucose loading on degradative enzymes is
      unknown. Primary cultures of rat mesangial cells were grown until confluent in
      the presence of fetal calf serum (FCS) and insulin (0.67 U/ml). Cells were then
      cultured for 7 days in plastic wells in either 10 or 30 mmol/l glucose media
      containing neither FCS nor insulin. Collagenase activity in media were determined
      by zymography and quantitative spectrofluorometry. Cathepsin B and D activities
      in cell extracts were measured by spectrofluorometry (using the fluorescent
      substrate Z-Arg-Arg-7-amido-4-methylcoumarin) and 125I-labeled hemoglobin
      digestion, respectively. Gelatin-degrading activity of live mesangial cells was
      also determined. mRNA levels for collagenase IV, cathepsin B, and cathepsin D
      were determined by Northern analysis. A major band of collagenase activity with a
      molecular size of 72 kDa was observed in all mesangial cell media. Exposure of
      cells to high glucose media resulted in significant reductions in collagenase and
      cathepsin B activities as well as impairment in gelatin-degrading activity.
      Collagenase IV and cathepsin B and D mRNA levels were also decreased by glucose
      loading. To exclude the possibility that glucose loading was injurious to cells,
      3H-leucine uptake (as a measure of protein synthesis) and membrane alkaline
      phosphatase activity (as a biochemical marker of viability) were not affected by
      the high glucose condition.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7622000
TI  - Insulin action and glucose metabolism in nondiabetic control and NIDDM subjects.
      Comparison using human skeletal muscle cell cultures.
AB  - Myoblasts from human skeletal muscle were isolated from needle biopsy samples of
      vastus lateralis and fused to differentiated multinucleated myotubes. Specific
      high-affinity insulin and insulin-like growth factor I (IGF-I) binding, glucose
      transporter proteins GLUT1 and GLUT4, glycogen synthase and pyruvate
      dehydrogenase proteins, and their specific mRNAs were identified in fused
      myotubes. Insulin and IGF-I stimulated 2-deoxyglucose uptake twofold with half
      maximal stimulation by insulin at 0.98 +/- 0.12 nmol/l and maximal stimulation at
      17.5 nmol/l. Acute insulin treatment (33 nmol/l) doubled glycogen synthase
      activity and glucose incorporation into glycogen while increasing pyruvate
      dehydrogenase approximately 30%. In cells cultured from NIDDM subjects, both
      basal (6.9 +/- 1.0 vs. 13.0 +/- 1.7 pmol.mg protein-1.min-1) and acute insulin
      stimulated transport (13.5 +/- 2.0 vs. 22.4 +/- 1.3 pmol.mg protein-1.min-1) were
      significantly reduced compared with nondiabetic control subjects (both P < or =
      0.005). GLUT1 protein content of total membranes from NIDDM subjects was
      decreased compared with control subjects, while GLUT4 levels were similar between
      groups. A significant correlation (r = 0.65, P < or = 0.05) was present when
      maximal rates of insulin-stimulated glucose transport in cell culture from
      subjects were compared with their corresponding in vivo glucose disposal
      determined by hyperinsulinemic glucose clamp. In summary, differentiated human
      skeletal muscle cultures exhibit biochemical and molecular features of insulin
      stimulated glucose transport and intracellular enzyme activity comparable with
      the in vivo situation. Defective insulin-stimulated glucose transport persists in
      muscle cultures from NIDDM subjects and resembles the reduced insulin-mediated
      glucose uptake present in vivo. We conclude that this technique provides a
      relevant cellular model to study insulin action and glucose metabolism in normal
      subjects and determine the mechanisms of insulin resistance in NIDDM.

PMID- 7622001
TI  - Kinetics of insulin action in vivo. Identification of rate-limiting steps.
AB  - To examine the kinetic steps in insulin's in vivo action, we have assessed the
      temporal relationship between arterial insulin, interstitial insulin, glucose
      disposal rate (GDR), and insulin receptor kinase (IRK) activity in muscle and
      between portal insulin, hepatic glucose production (HGP), and IRK activity in
      liver. Interstitial insulin, as measured by lymph-insulin concentration (muscle
      only), and IRK activity were used as independent methods to determine the arrival
      of insulin at its tissue site of action. Euglycemic clamps were conducted in
      seven mongrel dogs and consisted of an activation phase with a venous insulin
      infusion (7.2 nmol.kg-1.min-1, 100 min) and a deactivation phase. Liver and
      muscle biopsies were taken to assess IRK activity. Arterial, portal, and lymph
      insulin rose to 636 +/- 12, 558 +/- 18, and 402 +/- 24 pmol/l, respectively. GDR
      increased from 13.9 +/- 0.6 to 41.7 +/- 2.8, and HGP declined from 14.4 +/- 0.6
      to 1.1 +/- 0.6 mumol.kg-1.min-1. Muscle and liver IRK activity increased
      significantly from 5.9 +/- 0.9 to 14.6 +/- 0.6 and 5.5 +/- 0.7 to 23.7 +/- 1.9
      fmol P/fmol insulin receptor (IR), respectively. The time to half-maximum
      response (t1/2a) for stimulation of GDR (19.8 +/- 4.8 min) and suppression of HGP
      (21.5 +/- 3.7 min) were similar. The t1/2a for stimulation of GDR, muscle IRK,
      and rise in lymph insulin were not significantly different from one another and
      were all markedly greater than that for the approach to steady state of arterial
      insulin (2.3 +/- 1.2 min, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7622002
TI  - Insulin sensitivity accounts for glucose and lactate kinetics after intravenous
      glucose injection.
AB  - Mathematical modeling was used to explore the interaction between glucose,
      insulin, and lactate during the frequently sampled intravenous glucose tolerance
      test (FSIGTT). Insulin-modified FSIGTs were performed in 25 lean volunteers, and
      an additional 5 volunteers underwent FSIGTs with glucose injection alone to
      illustrate the effect of insulin on both glucose and lactate kinetics. The model
      chosen as the best representation of the system extended the minimal model of
      glucose kinetics (MM) by including a two-compartment model of lactate kinetics.
      The model accounted for both glucose and lactate kinetics, provided traditional
      MM parameters of insulin sensitivity and glucose effectiveness, and descriptive
      parameters of lactate kinetics. Modeling suggested that lactate production was
      limited by the rate of glucose disappearance, with no indication of direct
      effects of insulin on lactate. Inclusion of lactate kinetics had no adverse
      effect on MM parameters (SG: 0.023 +/- 0.009 vs. 0.023 +/- 0.010 min-1, SI: 1.01
      +/- 0.70 vs. 1.03 +/- 0.71 x 10(4).min-1.pmol-1.1; P > 0.50, lactate model vs.
      MM), and indicated that approximately 1.2% min-1 of total glucose disappearance
      during the FSIGT is converted to lactate. An additional benefit of including
      lactate kinetics was the significant improvement in precision in MM parameter
      estimates as reflected by the fractional standard deviations (FSDs). This effect
      was most prominent for SG, in which a threefold improvement in parameter
      precision was observed (FSD: 13.5 +/- 3.1 vs. 42.5 +/- 48.5; means +/-
      SD).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7622003
TI  - DR-BB rat thymus contains thymocyte populations predisposed to autoreactivity.
AB  - We have induced autoimmune insulin-dependent diabetes mellitus (IDDM) in athymic
      WAG rats by transfusing thymocytes from histocompatible phenotypically normal
      rats of the DR-BB strain. DR-BB rats rarely develop spontaneous IDDM, but readily
      become hyperglycemic if depleted in vivo of regulatory T-cells that express the
      RT6.1 maturational alloantigen. Successful adoptive transfer of IDDM by DR-BB
      thymocytes required that the athymic recipients be depleted of emerging
      populations of donor-origin RT6.1+ T-cells. Thymocytes from both normal and RT6
      depleted diabetic DR donors were equally capable of transferring autoimmunity. In
      contrast, thymocytes from normal histocompatible YOS rats failed to transfer
      IDDM. The autoreactive potential of DR-BB rat thymocytes was minimal from birth
      to 4 weeks of age and then increased substantially at 8-9 weeks of age. These
      results demonstrate that the DR-BB rat thymus harbors abnormal cell populations
      predisposed to autoreactivity. The data localize the developmental defect leading
      to diabetes in the BB rat to an abnormal intrathymic selection process.

PMID- 7622004
TI  - The relationship of glycemic exposure (HbA1c) to the risk of development and
      progression of retinopathy in the diabetes control and complications trial.
AB  - The Diabetes Control and Complications Trial (DCCT) demonstrated that a regimen
      of intensive therapy aimed at maintaining near-normal blood glucose values
      markedly reduces the risks of development or progression of retinopathy and other
      complications of insulin-dependent diabetes mellitus (IDDM) when compared with a
      conventional treatment regimen. This report presents an epidemiological
      assessment of the association between levels of glycemic exposure (HbA1c) before
      and during the DCCT with the risk of retinopathy progression within each
      treatment group. The initial level of HbA1c observed at eligibility screening as
      an index of pre-DCCT glycemia and the duration of IDDM on entry were the dominant
      baseline predictors of the risk of progression. The shorter the duration of IDDM
      on entry, the greater were the benefits of intensive therapy. In each treatment
      group, the mean HbA1c during the trial was the dominant predictor of retinopathy
      progression, and the risk gradients were similar in the two groups; a 10% lower
      HbA1c (e.g., 8 vs. 7.2%) is associated with a 43% lower risk in the intensive
      group and a 45% lower risk in the conventional group. These risk gradients
      applied over the observed range of HbA1c values and were unaffected by adjustment
      for other covariates. Over the range of HbA1c achieved by DCCT intensive therapy,
      there does not appear to be a level of glycemia below which the risks of
      retinopathy progression are eliminated. The change in risk over time, however,
      differed significantly between the treatment groups, the risk increasing with
      time in the study in the conventional group but remaining relatively constant in
      the intensive group. The risks were compounded by a multiplicative effect of the
      level of HbA1c with the duration of exposure (time in study). Total glycemic
      exposure was the dominant factor associated with the risk of retinopathy
      progression. When examined simultaneously within each treatment group, each of
      the components of pre-DCCT glycemic exposure (screening HbA1c value and IDDM
      duration) and glycemic exposure during the DCCT (mean HbA1c, time in study, and
      their interaction) were significantly associated with risk of retinopathy
      progression. Similar results also apply to other retinopathic, nephropathic, and
      neuropathic outcomes. The recommendation of the DCCT remains that intensive
      therapy with the goal of achieving near-normal glycemia should be implemented as
      early as possible in as many IDDM patients as is safely possible.

PMID- 7622006
TI  - Significance of glutathione depletion and oxidative stress in early embryogenesis
      in glucose-induced rat embryo culture.
AB  - Recent studies have demonstrated the protective effects of supplementing free
      oxygen radical scavenging enzymes against hyperglycemia-induced embryonic
      malformations. In this study, the glutathione (GSH)-dependent protection system
      in hyperglycemia-induced embryopathy was investigated. Rat embryos at the early
      head-fold stage (day 9.5) cultured in 66.7 mmol/l glucose for 48 h showed
      significant growth retardation and an increase in the frequency of malformations.
      The concentration of GSH and activity of the rate-limiting GSH-synthesizing
      enzyme, gamma-glutamylcysteine synthetase (gamma-GCS), significantly decreased in
      embryos exposed to hyperglycemia compared with controls (7.9 +/- 0.6 vs. 12.5 +/-
      0.9 nmol/mg protein, P < 0.01 and 13.3 +/- 1.9 vs. 22.6 +/- 1.1 microU/mg
      protein, P < 0.01, respectively). Decreased activity of gamma-GCS in embryos
      exposed to hyperglycemia was associated with decreased expression of gamma-GCS
      mRNA levels. However, the activities of superoxide dismutase and glutathione
      peroxidase did not significantly change in these embryos. Extracellular and
      intracellular free oxygen radical formations estimated by Lucigenin-dependent
      chemoluminescence and flow cytometric analysis using 2',7'-dichlorofluorescein
      diacetate increased in isolated embryonic cells taken from embryos cultured under
      hyperglycemia. Supplementation of 2 mmol/l GSH ester into the hyperglycemic
      culture nearly restored GSH concentration in these embryos (11.9 +/- 0.5 vs. 12.5
      +/- 0.9 nmol/mg protein) and reduced the formation of free oxygen radical species
      leading to almost complete normalization of growth retardation and embryonic
      dysmorphogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7622005
TI  - Insulin secretory defect in Zucker fa/fa rats is improved by ameliorating insulin
      resistance.
AB  - The role of insulin resistance in the impaired glucose-stimulated insulin release
      of Zucker fatty rats was investigated using the insulin-sensitizing
      thiazolidinedione drug pioglitazone. Fatty rats had fasting hyperinsulinemia yet
      a blunted secretory response to intravenous glucose compared with lean age
      matched controls. Islets from fatty rats secreted less insulin (based on islet
      DNA) in response to high glucose than islets from lean rats but secreted normal
      amounts of insulin when tolbutamide or alpha-ketoisocaproic acid (alpha-KIC) was
      the stimulus. Administering pioglitazone for 9 days diminished basal
      hyperinsulinemia and increased the insulin response to high glucose by fatty rats
      but not by lean controls. Pioglitazone pretreatment augmented the secretory
      response by isolated islets to high glucose, alpha-KIC, and tolbutamide.
      Augmentation of islet insulin release was not associated with reduced plasma
      glucose concentration, suggesting that altered glycemia was not involved.
      Pancreas and islet insulin content was greater in fatty rats than in lean
      controls and was decreased by pioglitazone; hence, insulin stores and glucose
      stimulated insulin release did not correlate. Pioglitazone treatment did not
      affect the rate of islet glucose usage or ATP/ADP in the presence of 2.75 or 16
      mmol/l glucose. These data indicate that ameliorating insulin resistance reverses
      defective glucose-stimulated insulin release by Zucker fa/fa rats. After
      pioglitazone administration, insulin secretion may be augmented by increased
      generation of a metabolic coupling factor from glucose or at a later step in the
      secretory process that is common to both glucose and nonglucose secretagogues.

PMID- 7622007
TI  - Identification of microsatellite markers near the human ob gene and linkage
      studies in NIDDM-affected sib pairs.
AB  - Non-insulin-dependent diabetes mellitus (NIDDM) is a complex metabolic disorder
      with a significant genetic component. Obesity is a frequent complicating factor
      for NIDDM. In the mouse, a number of single gene defects that result in obesity
      have been described. Mutations in one of these genes, the ob gene, results in
      both obesity and NIDDM. Recently, the cloning of the murine ob gene and its human
      homologue has been reported (Nature 372:425-432, 1994). In the present study, the
      contribution of genetic variation at the human ob locus to NIDDM susceptibility
      was assessed by analyzing allele sharing in NIDDM-affected sib pairs (ASPs) for
      markers located near the human ob gene. Four yeast artificial chromosome clones
      containing the human ob gene were isolated. These clones colocalized the ob gene
      and two microsatellite markers, D7S514 and D7S635, to a region of 280 kb on the
      long arm of human chromosome 7. The microsatellite markers were typed in 346
      Mexican-American NIDDM-ASPs derived from 176 families and an additional 110
      ethnically and geographically matched controls. No evidence of linkage or
      association between either microsatellite marker and NIDDM was observed in this
      population. These results suggest genetic variation in the human ob gene does not
      play a major role in susceptibility to NIDDM in Mexican-Americans.

PMID- 7622008
TI  - Expression of gicerin in development, oncogenesis and regeneration of the chick
      kidney.
AB  - Neurite outgrowth factor, which promotes neurite extension from neuronal cells,
      is an extracellular matrix glycoprotein belonging to the laminin family. Gicerin
      is a protein that binds neurite outgrowth factor. Its cDNA cloning has revealed
      that it is a novel cell adhesion molecule belonging to the immunoglobulin super
      family. Functional analysis demonstrates that gicerin possesses homophilic
      binding activity as well as heterophilic binding activity with neurite outgrowth
      factor. We examined the role and expression of neurite outgrowth factor and
      gicerin in chick kidney during development. In the embryonic kidney, gicerin was
      found to be highly expressed both on ureteric bud cells and metanephrogenic
      mesenchymal cells, when the mesenchymal cells become condensed to be converted
      into polarized epithelial cells. In the adult kidney, the expression of gicerin
      was decreased and restricted to the glomerulus, proximal tubule and medullary
      loop. On the other hand, neurite outgrowth factor was constitutively expressed in
      the basement membranes of tubules and the matrices of glomeruli during
      development. As some molecules which are expressed during embryogenesis and
      suppressed after maturation are re-expressed in tumor cells or tissues during
      regeneration, we also examined the expression of gicerin in chicken Wilms' tumor
      and regenerating kidney in interstitial nephritis. Gicerin was remarkably
      upregulated in Wilms' tumor and re-expressed in collecting ducts recovering from
      interstitial nephritis. These findings suggest that gicerin could play a role not
      only in normal renal development but also in oncogenesis and regeneration.

PMID- 7622009
TI  - Influence of cell type on the steroidogenic potential and basal cyclic AMP levels
      of ras-oncogene-transformed rat cells.
AB  - Transformation with ras oncogenes causes loss, maintenance or modulation of
      differentiation, depending on the developmental history of the target cells. In
      the present study, we examined steps in signal transduction that may underlie
      some of this variation, using steroidogenic cells of adult rats as the model
      system. Steroidogenesis in normal cells is regulated by cyclic AMP and protein
      kinase A (the cAMP/PKA pathway). We showed previously that transformation with v
      Ki-ras induces constitutive progesterone secretion in ovarian and adrenocortical
      cells that are normally steroidogenic (ovarian granulosa and adrenal glomerulosa
      cells) and also in developmentally related cells that are normally
      nonsteroidogenic (ovarian surface epithelium and adrenal capsular fibroblasts),
      but not in unrelated nonsteroidogenic cells, such as muscle fascia fibroblasts
      and peritoneal mesothelium. In the present study, basal cAMP levels in all
      transformed ovarian and adrenal cell-lines were increased over basal levels in
      normal cells, and of transformed muscle fascia and mesothelial cell-lines. As in
      normal cells, transformation-induced steroidogenesis was stimulated by cAMP and
      was PKA dependent. A comparison of malignancy-related characteristics showed that
      transformed cells from nonsteroidogenic organs were more tumorigenic in vivo and
      less sensitive to growth inhibition by cAMP in vitro than transformed ovarian and
      adrenocortical cells. The results show that the abnormal, constitutive
      steroidogenesis induced by the viral form of the Kirsten ras oncogene (v-Ki-ras)
      in certain cell types is associated with tissue-specific increases in basal cAMP
      levels. Thus, although the ras oncogenes function primarily through other signal
      transduction pathways, transformation with ras oncogenes alters PKA-mediated
      signal transduction in a manner that is developmentally determined.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7622011
TI  - Human intestinal development in a severe-combined immunodeficient xenograft
      model.
AB  - The present work describes a severe-combined immunodeficient murine xenograft
      model used to investigate human gastrointestinal ontogenesis. Specifically, the
      study has tested whether carefully selected regions of human fetal gut are able
      to undergo region-specific morphogenesis and epithelial cytodifferentiation when
      transplanted subcutaneously into immunodeficient mice. In addition, double-label
      in situ hybridisation techniques, utilising specific human and mouse DNA probes,
      have been adopted to characterise host and donor cell types and to investigate
      the potential developmental roles for non-epithelial cells in the regulation of
      epithelial differentiation pathways in vivo. Human fetal small and large bowel
      developed to form a characteristic mucosa 10 weeks after transplantation, which
      displayed clear region-specific structural and functional gradients. The initial
      phase of xenograft epithelialisation closely resembled the stratified type of
      epithelium which is present during early fetal gastrointestinal development.
      Idiosyncratic epithelial differentiation pathways were recorded during xenograft
      regeneration, with an absence of Paneth cells and an abundance of enteroendocrine
      cells when compared with developed xenograft and paediatric intestine. Such
      differences may, therefore, be important in ensuring rapid and region-specific
      development in the absence of conventional luminal stimuli and hormonal changes
      that occur normally during pregnancy. In situ hybridisation demonstrated an
      exclusively human origin for the intestinal xenograft epithelium and muscularis
      mucosa and externa. Although the submucosa and lamina propria were comprised of a
      chimeric mixture, murine cells were rarely seen to contact with the epithelium,
      which interacted primarily with human myofibroblasts and human intraepithelial
      lymphocytes. It is proposed that a 'selection' process operates to maintain
      species-specific cellular interactions, and this mechanism may subsequently play
      an important role in regulating epithelial cell differentiation, orchestrated in
      part by juxtaposed non-epithelial cell types.

PMID- 7622010
TI  - Expression of Flt3 tyrosine kinase receptor gene in mouse hematopoietic and
      nervous tissues.
AB  - The Flt3 gene encodes a tyrosine kinase receptor highly related to the Kit and
      Fms gene products. We have studied the expression of Flt3 by using in situ
      hybridization of mouse tissue sections. The results show that Flt3 RNAs are
      present in certain regions of lymphohematopoietic organs, placenta and nervous
      system. Flt3 is expressed in the medullary area of fetal and newborn thymus, in
      the paracortical regions of lymph nodes and in the red pulp of spleen. In
      placenta, labyrinthine trophoblasts express Flt3. Finally, Flt3 RNAs are found in
      several regions of the brain and in cerebellar Purkinje cells. Western-blot
      analysis showed that the FLT3 protein is present in the tissues positive for Flt3
      RNA expression. Our observations allow for a comparison with the distribution of
      the Kit gene and analysis of a possible redundancy between KIT and FLT3
      receptors.

PMID- 7622012
TI  - Olfactory origins and evolution of the brain-pituitary endocrine system: facts
      and speculation.

PMID- 7622014
TI  - Cortisol induces stress-related changes in the skin of rainbow trout
      (Oncorhynchus mykiss).
AB  - The ultrastructure of the skin of rainbow trout, Oncorhynchus mykiss, was studied
      over a 7-day period after a single meal containing cortisol. The fish experienced
      increased plasma cortisol levels for 1 day. Pavement cells contained
      significantly more vesicles of high electron density, which were also numerous in
      deeper filament cells, and displayed peroxidase activity. Mitotic cells were
      common after 4 and 7 days. Increased apoptosis, taken to indicate accelerated
      ageing, was detected in both pavement and mucous cells. Newly differentiated
      mucous cells were found close to skin surface, and many mucous cells contained
      mucosomes of high electron density. The basal lamina became highly folded. The
      low numbers of leukocytes present in the skin did not change noticeably, but
      substantially more lymphocytes were apoptotic. The melanosomes in the pigment
      initially dispersed and subsequently reaggregated in the cell bodies of these
      cells. The reaggregation was accompanied by apoptosis of melanocyte extensions.
      The results demonstrate the ability of the hormone to regulate several of the
      effects observed in the skin of fish challenged by stressors. Other phenomena
      generally observed in stressed fish, such as pavement cell necrosis and massive
      leucocyte infiltration, were not found after cortisol treatment. The latter
      observation indicates that regulatory factors in addition to cortisol must be
      operative during stress.

PMID- 7622015
TI  - The American bullfrog (Rana catesbeiana) exhibits differential cardiovascular
      responses to LTC4 after short- and long-term cold exposure.
AB  - Mean arterial pressure (MAP) and heart rate (HR) responses to leukotriene (LT)C4
      have been studied in warm (W-A) and cold-acclimated (C-A) America bullfrogs, Rana
      catesbeiana, but nothing is known about how the length of cold treatment affects
      the response to LTC4 or how responses are affected by return to room temperature
      following cold exposure. In this study, two groups of frogs were placed at 5
      degrees either for 30 days (C-A) or for 1 day (W-C) and LTC4 dose-response curves
      obtained at 5 degrees. After the frogs were removed from cold, the baseline MAP
      and HR were monitored for 120 min, and dose-response curves were repeated at 2,
      24, and 48 hr. The LTC4 dose-response curves were also obtained during the three
      experimental days on frogs which had never been placed at cold temperature (W-A).
      C-A frogs showed greater MAP response than W-C frogs at 5 degrees, and also
      showed the greatest MAP response of the three groups 48 hr after the animals were
      removed from cold temperature. These data suggest that up regulation of LTC4
      receptors may have occurred in C-A frogs. Cold exposure alone eliminated reflex
      HR response to LTC4 in both C-A and W-C groups. Longer duration of action was
      also observed in these groups. The results demonstrate that short-term cold
      exposure can affect the response to LTC4 in frogs, but that physiological
      adjustments occur in frogs undergoing long-term exposure.

PMID- 7622013
TI  - Immunohistochemical localization of neurotensin in a subpopulation of
      noradrenergic chromaffin cells of the adrenal gland of the flat snake
      (Waglerophis merremii).
AB  - The distribution of neurotensin (NT)-like immunoreactivity (LI) in the adrenal
      gland of the snake Waglerophis merremii has been examined immunohistochemically.
      Double staining, combining NT with tyrosine hydroxylase (TH) or calcitonin gene
      related peptide (CGRP) antibodies and TH with CGRP antibodies, was also carried
      out. Results were analyzed by conventional and by confocal fluorescence
      microscopy. Immunostaining revealed a subpopulation of chromaffin cells
      containing NT-LI within the dorsal noradrenergic ribbon. In addition, there were
      some NT-immunoreactive (IR) fibers in this region. NT immunoreactivity was not
      present within adrenergic chromaffin cells or in cortical tissue. Double staining
      revealed CGRP-IR fibers innervating most of the chromaffin adrenergic cells.
      Within the dorsal noradrenergic ribbon, two groups of chromaffin TH-IR cells were
      present, one receiving a dense CGRP-IR innervation and another without contact
      with CGRP-IR terminals. The latter chromaffin cells displayed NT-LI. These
      results show, for the first time, the presence of a neuropeptide in chromaffin
      noradrenergic cells of a reptilian adrenal gland and open up the possibility that
      other peptides may also be present in these cells.

PMID- 7622016
TI  - Thyrotropin-releasing hormone receptors in the pituitary of rainbow trout
      (Oncorhynchus mykiss).
AB  - Binding parameters of radiolabeled pGlu-3-Me-His2-Pro-NH2 ([3H]MeTRH) to
      pituitary TRH receptors of rainbow trout (Oncorhynchus mykiss) and goldfish
      (Carassius auratus) were investigated. Washed pituitary membranes were incubated
      with [3H]MeTRH in the absence (B0) or presence of TRH or TRH analogs under
      various paradigms. Specific binding (Bsp) was thermolabile and tissue dependent.
      Association of Bsp was slow (k + 1 = 1.43 x 10(7) M-1 min-1) achieving
      equilibrium binding after 60 min, and remaining stable for at least 60 min.
      Thereafter, equilibrium-bound [3H]MeTRH was dissociated by addition of excess
      MeTRH; estimated dissociation rate constant (k - 1) and half-life (t1/2) were
      6.74 x 10(-2) min-1 and 10.2 min, respectively, with a kinetically derived
      dissociation constant (k - 1/k + 1) of 4.71 x 10(-9) M. [3H]MeTRH binding was
      differentially displaced by TRH and TRH analogs. LIGAND analysis of multiple
      homologous (MeTRH) and heterologous (TRH) displacement experiments indicates the
      presence of a single class of binding sites with nanomolar affinity. Data pooled
      from multiple heterologous (TRH) displacement experiments suggested the presence
      of an additional class of higher-affinity (picomolar) binding sites.
      Additionally, examination of separate preparations of neurointermediate lobes and
      pars distalis from trout and goldfish suggested that these two classes of binding
      sites were differentially located between the two lobes. Specificity analysis of
      the trout pituitary TRH receptor indicates that the rank order of potency for
      [3H]MeTRH displacement was MeTRH > TRH > pGlu-Phe-Pro-NH2. Analogs with N- or C
      terminal substitutions had little competitive potential. This study indicates the
      presence and binding characteristics of specific TRH receptors in the salmonid
      and cyprinid pituitary gland.

PMID- 7622017
TI  - Modulatory effects of biogenic amines on adipokinetic hormone secretion from
      locust corpora cardiaca in vitro.
AB  - The control of the release of adipokinetic hormones from neurosecretory cells
      within the glandular lobes of the corpus cardiacum involving axons running
      through the paired nervus corporis cardiaci II is unclear. Cyclic-AMP (cAMP) is
      clearly a second messenger. The effects of four biogenic amines (octopamine,
      dopamine, tyramine, and serotonin) on the release of adipokinetic hormone-I were
      investigated in vitro. None had an effect on its own; they all potentiated the
      hormone release induced by cAMP-activating agents. Dopamine and serotonin were
      only present in the neurohemal part of the corpus cardiacum. Octopamine and
      tyramine were not detectable in the corpus cardiacum.

PMID- 7622019
TI  - Cortisol mediates the increase in intestinal fluid absorption in Atlantic salmon
      during parr-smolt transformation.
AB  - We have previously shown in Atlantic salmon that the rate of fluid absorption by
      the posterior intestine (Jv) is elevated during the smolt stage in spring as a
      preadaptive development for osmoregulation in seawater. In the present study, we
      examined developmental differences in the responsiveness of Jv to cortisol and
      the corticosteroid antagonist, RU 486, through the parr-smolt transformation.
      Freshwater, juvenile salmon were administered slow-release implants of cortisol
      (50 micrograms/g body wt), RU 486 (1 mg/g body wt), or the implant without
      steroid (controls) at seven times from November 1992 through June 1993. Seven and
      8 days after implantation, plasma cortisol concentrations and in vitro Jv were
      measured. In control salmon, both plasma cortisol and Jv peaked in April and were
      positively correlated over time. Cortisol implants stimulated Jv of salmon only
      during the parr and postsmolt stages, when Jv of controls was low. The exogenous
      cortisol was sufficient to stimulate Jv to a rate comparable to that measured for
      control salmon in the smolt stage. Conversely, RU 486 implants inhibited Jv only
      during the peak smolt period, when Jv of controls was elevated. Taken together,
      these results demonstrate that cortisol is a necessary and sufficient endocrine
      signal mediating this developmental change in intestinal function during parr
      smolt transformation. This is the first report of plasma cortisol levels measured
      in fish treated with RU 486. Plasma cortisol was elevated by RU 486, suggesting
      that this corticosteroid antagonist blocked feedback inhibition on the pituitary
      interrenal axis.

PMID- 7622018
TI  - Morphogenesis of the pancreas of Bufo bufo during metamorphosis.
AB  - Histology and immunohistochemical reactivity (IR) toward insulin, glucagon,
      somatostatin14, and pancreatic polypeptide were investigated in the pancreas and
      in other tissues of Bufo bufo during metamorphosis. Insulin IR cells appeared at
      the very beginning of metamorphosis among exocrine pancreatic cells rich in yolk
      platelets, not completely arranged in acini. Less than 1 week later, glucagon,
      somatostatin14, and pancreatic polypeptide IR cells also appeared. At metamorphic
      climax, both endocrine and exocrine tissues of the pancreas underwent extensive
      degeneration, mainly via apoptotic cellular death. At this time the number of IR
      cells and the intensity of immunohistochemical reactions decreased for all the
      hormones tested. Pancreatic reorganization began at the end of the climax.

PMID- 7622020
TI  - Angiotensin-I- and -III-mediated cardiovascular responses in the freshwater North
      American eel, Anguilla rostrata: effect of Phe8 deletion.
AB  - Cardiovascular responses to synthetic eel [Asn1, Val5, Gly9]-ANG-I, ANG-III (2
      8), and ANG-I (1-7) were measured in conscious and resting freshwater North
      American eels. Indwelling Doppler flow probes were placed on the ventral and
      dorsal aortas, a pressure catheter in the lienomesenteric artery, and a peptide
      delivery catheter in the caudal vein. Twenty-five and 150 ng.kg-1 ANG-III
      increased baseline cardiac output (CO) (15.23 +/- 0.31 ml.min-1.kg-1; n = 5) by
      23 and 47%, respectively, by increasing stroke volume (SV) but not heart rate
      (HR). ANG-I (150 ng.kg-1) also elevated CO (62%) by increasing both SV (44%) and
      HR (14%). Estimated branchial shunting (BS) was increased by 150 ng.kg-1 ANG-I
      and -III suggesting that more blood perfused the arteriovenous pathway in the
      gills. Dorsal aortic blood pressure (PDA) (3.08 +/- 0.12 kPa) was elevated by 150
      ng.kg-1 ANG-I (67%) and -III (52%). Pressor responses temporally preceded the
      blood flow increases and there was a significant increase in systemic vascular
      resistance (RSYS) at the peak pressor responses. At the peak flow responses,
      increased CO was solely responsible for the increase in PDA; RSYS had returned to
      baseline values. Pressor responses to ANG-III decayed more rapidly (18.6 min)
      compared with those of ANG-I and -II (36 min). ANG-I (1-7) had no measurable
      effect on cardiovascular function indicating that the carboxyl-terminal 8
      phenylalanine is an absolute requirement for the hormonal activity of angiotensin
      in fishes.

PMID- 7622021
TI  - Metacognitive and frontal lobe processes: at the interface of cognitive
      psychology and neuropsychology.
AB  - During the past several decades, research in both cognitive psychology and
      neuropsychology has become increasingly concerned with the processes that monitor
      and control human cognition. In the area of cognitive psychology, this research
      has focused on metacognition or metacognitive processes, and in the area of
      neuropsychology, it has focused on frontal lobe processes. It is evident that
      both areas have been referring to very similar concepts, with some variations,
      but with notably little acknowledgement of each other. The principal purpose of
      this study was to conduct an analysis of the main research within each of these
      areas and to examine the continuities and discontinuities in the theoretical
      premises and empirical results between the two areas. Results indicated that the
      two areas are remarkably similar in both theoretical premises and empirical
      results, but that cognitive psychology emphasizes monitoring and control, whereas
      neuropsychology tends to emphasize control only. A synthesis that unites the work
      in cognitive psychology and neuropsychology would supply many new directions for
      research.

PMID- 7622022
TI  - Perfectionism, humor, and optimism as moderators of health outcomes and
      determinants of coping styles of women executives.
AB  - Previous research has indicated that humor, optimism, and perfectionism are
      ubiquitous human tendencies and traits affecting the performance and coping
      styles of women in the work place. The purpose of the present series of studies
      was to provide a more rigorous test of the hypothesis that certain personality
      attributes buffer the impact of daily hassles on health outcomes among female
      executives. Three studies were conducted to examine how perfectionism, humor, and
      optimism moderate the deleterious effects of daily hassles on self-esteem,
      burnout, and physical health. Hierarchical multiple regression analyses revealed
      that all attributes significantly moderated the relationship between daily
      hassles and self-esteem maintenance, emotional exhaustion, and physical illness.
      A fourth study examined the correlations between high levels of perfectionism,
      humor, and optimism and female executives' use of different coping strategies and
      orientations. The results provide implications for the early socialization and
      management training of female executives working in stressful environments.

PMID- 7622023
TI  - [PCR genetic typing of pathogenic microorganisms].
AB  - Basic principles, characteristics, methodical peculiarities, and strategy of
      choice of PCR-mediated methods of genetic typing are discussed. Existing and
      potential fields of application of these methods for tackling many unsolved
      problems of molecular epidemiology of bacterial infections are considered.
      Advantages of PCR-mediated methods of genetic typing compared with other
      techniques used for studying genomic polymorphism are demonstrated. Possibilities
      for developing novel PCR-mediated methods with the aim of improving genetic
      typing are analyzed.

PMID- 7622024
TI  - [p53 with a mutation in codon 273 increases the probability of amplifying the
      dhfr gene in Rat-1 and LIM1215 cells].
AB  - The effect of the expression of the exogenous human mutant p53 (Arg-->His in
      codon 273) on the amplification rate of the gene dhfr in permissive Rat-1 and
      LIM1215 cells was studied. It was shown that injection of a retroviral
      construction with p53His273 resulted in the accumulation of methotrexate
      resistant variants with an increased number of dhfr copies in populations of
      recipient cells. Luria-Delbruck fluctuation analysis revealed a four- to six-fold
      increase in the rate of appearance of new methotrexate-resistant cells.
      Chromosomal analysis demonstrated an extrachromosomal location of amplified DNA
      in cells containing p53His273, as was the case for control sublines. The data
      obtained indicate that modifications of p53 may induce gene amplification not
      only via removing the proliferation block of cells with amplified genes in
      selective medium, but also via some other mechanisms, that seem to increase the
      chromosomal recombination rate.

PMID- 7622025
TI  - [2,4,6-trinitrotoluene and 2,4-diamino-6-nitrotoluene: the absence of recA
      dependent mutagenesis?].
AB  - The genotoxicity of 2,4,6-trinitrotoluene (2,4,6-TNT) and its amino derivative,
      2,4-diamino-6-nitrotoluene (2,4-DA-6-NT), was studied using the Escherichia coli
      tester strain PQ37 in the SOS chromotest. The compound 2,4,6-TNT, without
      metabolic activation, virtually failed to induce an SOS effect in cells of the
      tester bacteria. Consequently, mutagenic activity of 2,4,6-TNT, which was shown
      earlier in the Ames test, does not depend on SOS mutagenesis. It was demonstrated
      that metabolic activation with the microsomal S9 human placenta fraction results
      in a threefold increase in the induction factor of the SOS effect caused by 2,4,6
      TNT. The absence of the SOS-inducing activity of 2,4-DA-6-NT, regardless of the
      presence of a microsomal activating mixture, is shown. Thus, 2,4-DA-6-NT does not
      belong to metabolites of 2,4,6-TNT, responsible for the genotoxicity of this
      compound.

PMID- 7622026
TI  - [Polymorphism of t-specific DNA elements of the proximal part of chromosome 17 in
      mice of Mus genus].
AB  - To study structural organization and polymorphism of the proximal part of
      chromosome 17, a hybridization analysis of DNA from mice of different origin was
      carried out using four t-specific probes. Results of the analysis allow us to
      conclude that the DNA element copy number is quantitatively unstable and differs
      in distribution in both newly formed recombinant haplotypes and in wild-type
      chromosome 17. probe Tu66 was used to study D17Leh66-element organization of Mus
      abbotti and Mus hortulanus mice. Three types of D17Leh66-elements were identified
      in the genomes of these species. The copy number of each type of DNA element
      varied in the genome of each of four studied species. Homologs to t-specific Tu66
      and Tu119 probes were found in the genome of Rattus norvegicus rat. The data
      obtained are discussed with respect to the evolution of the proximal part of Mus
      mouse chromosome 17.

PMID- 7622027
TI  - [Cytogenetic effects of pheromones on bone marrow cells in male Mus musculus L.
      mice].
AB  - Young male CBA/LacStoRap mice were exposed for two hours to volatile components
      of native or dialyzed urine (VC or VCd, respectively) of mature males of the same
      line. To estimate the effects of VC and VCd on bone marrow cells, cytogenetic
      analysis of mitotic disturbances in anaphase-telophase cells was performed. The
      overall frequency of mitotic disturbances in VC-treated mice became significantly
      higher 24 and 48 h after exposure but returned to the initial level 72 h after
      exposure (P < 0.05). Similar effects were observed after 24 h in mice exposed to
      VCd. These results suggest that VC and VCd are capable of disturbing the
      stability of genetic processes in proliferating bone marrow cells. Evidence was
      also obtained that these components are associated with major urinary proteins.
      The significance and possible mechanisms of effects observed in the study are
      discussed.

PMID- 7622028
TI  - [Terminalization of chiasmata. Analysis of the phenomenon].
AB  - On the basis of my own and published data, a conclusion was made that meiotic
      terminalization of chiasmata, which was postulated by Darlington, does not occur.
      The chiasmata remain in the sites where they appear, until the disjunction of
      homologous chromosomes in meiotic anaphase I. The disjunction of homologues is
      accounted for by repulsion of the sister chromatids.

PMID- 7622029
TI  - [The Drosophila melanogaster Adh locus upon selection for delayed aging].
AB  - Dynamics of the Adh activity and frequencies of alleles AdhF and AdhS were
      analyzed under selection for delayed senescence. The experiments were performed
      on Drosophila melanogaster. Lines AdhS cn and AdhF vg and experimental
      populations cn and vg, selected for an increased duration of reproductive period
      (late oviposition) were used. Analysis of fertility, longevity, viability and
      resistance to starvation showed that selection for late oviposition resulted in
      delayed senescence of flies of the experimental populations. Genetic structure of
      population vg changed considerably with regard to the Adh locus. This was
      confirmed by parameters of activity, thermostability and electrophoretic mobility
      of the enzyme isolated from flies after 30 generations of selection. Analysis of
      frequencies of the Adh alleles showed that in both selected populations, which
      initially had different genetic composition, accumulated allele AdhS, which
      encodes the isozyme that is less active but more resistant to inactivation.
      Genetic mechanism of delayed senescence in Drosophila is assumed to involve
      selection at vitally important enzyme loci, including Adh.

PMID- 7622030
TI  - [Genetic structure of various native and commercial breeds of cattle (Bos taurus)
      from Eurasia].
AB  - On the basis of polymorphism of genes, controlling seven blood and four milk
      proteins, genetic structure and main variation parameters were analyzed in 27
      breeds of cattle, 11 of which were native. Difference in allele frequencies of
      blood proteins were detected in the Jersey (island form) and Yakut
      (geographically isolated form) breeds; in milk proteins, the Yaroslavl' breed
      differed from the other breeds. Native breeds generally had a more specialized
      genetic structure than commercial breeds. They had a greater deficit of
      heterozygotes, which is probably related to the small number of individuals in
      this breed group and their high homozygosity. An analysis of inter- and
      intrapopulation diversity showed differences in groups of commercial and native
      breeds that depended on the intensity of selection in populations.

PMID- 7622031
TI  - [Distribution of haptoglobin types and their significance in biochemical and
      immunologic indicators in persons exposed to low radiation doses].
AB  - Haptoglobin (Hp) polymorphism and its significance for changes in biochemical and
      immunological parameters was analyzed in personnel of a nuclear plant receiving
      doses of external and internal irradiation close to maximum permissible levels.
      The distribution of Hp types and frequencies of alleles Hp in the group of
      probands asa a whole (1-1 - 14.1%; 2-1 - 49.2%; and 2-2 - 36.7%) and in probands
      subjected to different types and doses of irradiation (1-1, 13.6 - 16.0%; 2-1,
      47.8 - 50.5%; and 2-2:35.8 - 38.2%) did not differ from those expected or from
      corresponding parameters of the control group and population. An increase in the
      frequency of allele Hp was observed for persons over 60 years of age. It was
      found that the levels of uric acid, the activities of acid phosphatase, lactate
      dehydrogenase, alkaline phosphatase and its isozymes, and the content of certain
      lymphocyte classes and immune complexes are initially higher in carriers of Hp
      type 1-1. In these probands, changes in certain parameters related to irradiation
      were observed less frequently. In some cases, opposite changes in immunological
      parameters were observed in persons with different Hp types after internal
      irradiation.

PMID- 7622032
TI  - [Effect of the preparation "Loshtak" on the clastogenic activity
      cyclophosphamide].
AB  - The anticlastogenic effect of the herbal preparation Loshtak on rats and mice was
      tested using the same scheme of treatment and doses of the preparation as are
      employed in medical practice. It was shown that intragastric administration of
      Loshtak results in a statistically significant decrease in the clastogenic effect
      of cyclophosphamide injected 48 h after the end of treatment with Loshtak. High
      doses of Loshtak did not induce any increase in the number of micronuclei in
      mouse bone marrow cells. Possible mechanisms responsible for the anticlastogenic
      effect of Loshtak are discussed.

PMID- 7622033
TI  - The POU domain: versatility in transcriptional regulation by a flexible two-in
      one DNA-binding domain.

PMID- 7622034
TI  - The head involution defective gene of Drosophila melanogaster functions in
      programmed cell death.
AB  - Deletions of chromosomal region, 75C1,2 block virtually all programmed cell death
      (PCD) in the Drosophila embryo. We have identified a gene previously in this
      interval, reaper (rpr), which encodes an important regulator of PCD. Here we
      report the isolation of a second gene in this region, head involution defective
      (hid), which plays a similar role in PCD. hid mutant embryos have decreased
      levels of cell death and contain extra cells in the head. We have cloned the hid
      gene and find that its expression is sufficient to induce PCD in cell death
      defective mutants. The hid gene appears to encode a novel 410-amino-acid protein,
      and its mRNA is expressed in regions of the embryo where cell death occurs.
      Ectopic expression of hid in the Drosophila retina results in eye ablation. This
      phenotype can be suppressed completely by expression of the anti-apoptotic p35
      protein from baculovirus, indicating that p35 may act genetically downstream from
      hid.

PMID- 7622035
TI  - Cell proliferation and DNA replication defects in a Drosophila MCM2 mutant.
AB  - The yeast MCM2, MCM3, and MCM5/CDC46 genes are required for DNA replication and
      have been proposed to act as factors that license the DNA for one and only one
      round of replication per cell cycle. We have identified a Drosophila gene,
      DmMCM2, that is highly homologous to MCM2. A P-element insertion into this gene,
      which prevents its transcription, inhibits proliferation of cells in the imaginal
      discs and central nervous system (CNS) and causes an apparent prolongation of S
      phase in the embryonic and larval CNS. DmMCM2 is expressed in the embryo in a
      pattern corresponding to that of S-phase cells. These results suggest that DmMCM2
      plays a role in the regulation of DNA replication analogous to that of its yeast
      counterpart.

PMID- 7622036
TI  - Histone H4 and the maintenance of genome integrity.
AB  - The normal progression of Saccharomyces cerevisiae through nuclear division
      requires the function of the amino-terminal domain of histone H4. Mutations that
      delete the domain, or alter 4 conserved lysine residues within the domain, cause
      a marked delay during the G2+M phases of the cell cycle. Site-directed
      mutagenesis of single and multiple lysine residues failed to map this phenotype
      to any particular site; the defect was only observed when all four lysines were
      mutated. Starting with a quadruple lysine-to-glutamine substitution allele, the
      insertion of a tripeptide containing a single extra lysine residue suppressed the
      G2+M cell cycle defect. Thus, the amino-terminal domain of histone H4 has novel
      genetic functions that depend on the presence of lysine per se, and not a
      specific primary peptide sequence. To determine the nature of this function, we
      examined H4 mutants that were also defective for G2/M checkpoint pathways.
      Disruption of the mitotic spindle checkpoint pathway had no effect on the
      phenotype of the histone amino-terminal domain mutant. However, disruption of
      RAD9, which is part of the pathway that monitors DNA integrity, caused precocious
      progression of the H4 mutant through nuclear division and increased cell death.
      These results indicate that the lysine-dependent function of histone H4 is
      required for the maintenance of genome integrity, and that DNA damage resulting
      from the loss of this function activates the RAD9-dependent G2/M checkpoint
      pathway.

PMID- 7622037
TI  - MSH5, a novel MutS homolog, facilitates meiotic reciprocal recombination between
      homologs in Saccharomyces cerevisiae but not mismatch repair.
AB  - Using a screen designed to identify yeast mutants specifically defective in
      recombination between homologous chromosomes during meiosis, we have obtained new
      alleles of the meiosis-specific genes, HOP1, RED1, and MEK1. In addition, the
      screen identified a novel gene designated MSH5 (MutS Homolog 5). Although Msh5p
      exhibits strong homology to the MutS family of proteins, it is not involved in
      DNA mismatch repair. Diploids lacking the MSH5 gene display decreased levels of
      spore viability, increased levels of meiosis I chromosome nondisjuction, and
      decreased levels of reciprocal exchange between, but not within, homologs. Gene
      conversion is not reduced. Msh5 mutants are phenotypically similar to mutants in
      the meiosis-specific gene MSH4 (Ross-Macdonald and Roeder 1994). Double mutant
      analysis using msh4 msh5 diploids demonstrates that the two genes are in the same
      epistasis group and therefore are likely to function in a similar process-
      namely, the facilitation of interhomolog crossovers during meiosis.

PMID- 7622038
TI  - p107 uses a p21CIP1-related domain to bind cyclin/cdk2 and regulate interactions
      with E2F.
AB  - The kinase activities of the cyclin/cdk complexes can be regulated in a number of
      ways. The most recently discovered mechanism of regulation is the association of
      cdk inhibitors (CKIs), such as p21, p27, and p57, with these complexes. In this
      report we demonstrate that the pRB-related protein p107, like the p21 family of
      cdk inhibitors, can inhibit the phosphorylation of target substrates by cyclin
      A/cdk2 and cyclin E/cdk2 complexes, and the associations of p107 and p21 with
      cyclin/cdk2 rely on a structurally and functionally related interaction domain.
      Furthermore, interactions between p107 or p21 with cyclin/cdk2 complexes are
      mutually exclusive. In cells treated with DNA-damaging agents elevated levels of
      p21 cause a dissociation of p107/cyclin/cdk2 complexes to yield p21/cyclin/cdk2
      complexes. Finally, the consequences of cyclin/cdk2 interactions with p107 have
      been examined. The activation of the p107-bound cyclin/cdk kinases leads to
      dissociation of p107 from the transcription factor E2F. Together, these results
      suggest that cyclin/cdk complexes can be regulated by protein molecules from
      different families in a mutually exclusive manner in response to certain signals
      and that these inhibitory proteins may have a potential role in regulating
      macromolecular assembly.

PMID- 7622040
TI  - Patterns of gene action in plant development revealed by enhancer trap and gene
      trap transposable elements.
AB  - The crucifer Arabidopsis thaliana has been used widely as a model organism for
      the study of plant development. We describe here the development of an efficient
      insertional mutagenesis system in Arabidopsis that permits identification of
      genes by their patterns of expression during development. Transposable elements
      of the Ac/Ds system carrying the GUS reporter gene have been designed to act as
      enhancer traps or gene traps. A novel selection scheme maximizes recovery of
      unlinked transposition events. In this study 491 plants carrying independent
      transposon insertions were generated and screened for expression patterns. One
      half of the enhancer trap insertions and one-quarter of the gene trap insertions
      displayed GUS expression in seedlings or flowers, including expression patterns
      specific to organs, tissues, cell types, or developmental stages. The patterns
      identify genes that act during organogenesis, pattern formation, or cell
      differentiation. Transposon insertion lines with specific GUS expression patterns
      provide valuable markers for studies of Arabidopsis development and identify new
      cell types or subtypes in plants. The diversity of gene expression patterns
      generated suggests that the identification and cloning of Arabidopsis genes
      expressed in any developmental process is feasible using this system.

PMID- 7622039
TI  - Overexpression of HOXB4 in hematopoietic cells causes the selective expansion of
      more primitive populations in vitro and in vivo.
AB  - Hox genes were first recognized for their role in embryonic development and may
      also play important lineage-specific functions in a variety of somatic tissues
      including the hematopoietic system. We have recently shown that certain members
      of the Hox A and B clusters, such as HOXB3 and HOXB4, are preferentially
      expressed in subpopulations of human bone marrow that are highly enriched for the
      most primitive hematopoietic cell types. To assess the role these genes may play
      in regulating the proliferation and/or differentiation of such cells, we
      engineered the overexpression of HOXB4 in murine bone marrow cells by retroviral
      gene transfer and analyzed subsequent effects on the behavior of various
      hematopoietic stem and progenitor cell populations both in vitro and in vivo.
      Serial transplantation studies revealed a greatly enhanced ability of HOXB4
      transduced bone marrow cells to regenerate the most primitive hematopoietic stem
      cell compartment resulting in 50-fold higher numbers of transplantable totipotent
      hematopoietic stem cells in primary and secondary recipients, compared with
      serially passaged neo-infected control cells. This heightened expansion in vivo
      of HOXB4-transduced hematopoietic stem cells was not accompanied by identifiable
      anomalies in the peripheral blood of these mice. Enhanced proliferation in vitro
      of day-12 CFU-S and clonogenic progenitors was also documented. These results
      indicate HOXB4 to be an important regulator of very early but not late
      hematopoietic cell proliferation and suggest a new approach to the controlled
      amplification of genetically modified hematopoietic stem cell populations.

PMID- 7622041
TI  - Detection of cleavage products from an in vivo transcribed cis hairpin ribozyme
      in turnips using the CaMV plant virus.
AB  - In order to examine ribozyme (Rz) activity in vivo, we have adapted a virus to
      deliver Rz to plants. DNA fragments that code for both active and mutant cis
      hairpin Rz were cloned into the double-stranded DNA plant virus, cauliflower
      mosaic virus (CaMV). These Rz constructs successfully infected Brassica
      campestris rapa (turnip). The plants that were infected with the active-Rz
      construct showed, on average, a one-week delay in the appearance of viral
      symptoms, when compared to the mutant-Rz control. Since CaMV replicates through
      reverse transcription of a full-length RNA intermediate, Rz cloned into the CaMV
      DNA should be transcribed within this viral RNA. If these Rz constructs cleave,
      the amount of intact virus RNA should be reduced, resulting in attenuated viral
      symptoms. In addition, lysate RNase protection assays showed fragments
      corresponding to the sizes of both the 5' and 3' cis cleavage products in the
      active Rz tissue. No cleavage products were observed from plant tissue infected
      with the mutant Rz. Both the attenuated systemic viral symptoms and the cleavage
      products from the protection assay strongly support in vivo transcription and
      cleavage of this hairpin Rz. This is the first report of an in vivo transcribed
      Rz showing cleaved products by direct RNA analysis (non-PCR) in plants or
      animals.

PMID- 7622042
TI  - Identification of two new exons and multiple transcription start points in the 5'
      untranslated region of the human cathepsin-B-encoding gene.
AB  - Transcripts for cysteine protease cathepsin B (CTSB) were found to be highly
      variable in the 5'-UTR (untranslated region). In cDNA clones from a human gastric
      adenocarcinoma cDNA library, we have identified two new exons (designated 2a and
      2b) between exons 2 and 3 in the 5'-UTR of the gene. All of the exons of the 5'
      UTR could be alternatively spliced to produce several transcript species. In
      addition, transcription was initiated from more than one promoter region. Using
      RT-PCR (reverse transcription-polymerase chain reaction) and primer extension
      assays, CTSB mRNA species were found to differ among tissues and between a
      glioblastoma sample and a cell line derived from it. Exons 2a and 2b were
      detected more frequently in tumor samples than in matched normal samples. Thus,
      factors related to the cell differentiation and environment seem likely to
      determine the types of transcripts that are expressed which in turn could
      influence the overall steady-state level of CTSB mRNAs and their rate of
      translation. Interestingly, at least three upstream translation initiation codons
      were observed and could constitute a means of controlling translation initiation.

PMID- 7622044
TI  - Transcriptional activation of the neuronal peripherin-encoding gene depends on a
      G + C-rich element that binds Sp1 in vitro and in vivo.
AB  - Peripherin (Prph) is a type-III intermediate filament (IF) protein principally
      synthesized in peripheral nervous system neurons. We have previously shown that
      three regulatory elements, PER1, PER2 and PER3, in the first 98 bp of the Prph
      gene promoter, were sufficient to direct cell-type specific expression of a
      reporter gene [Desmarais et al., EMBO J. 11 (1992) 2971-2980]. Of these elements,
      PER1 was found to be important for cell-type specificity, but required the
      presence of other elements for transcriptional activity. Here, we show that PER3
      is a stronger activator than PER2 and that it can stimulate cell-type-specific
      transcription when combined with PER1. We have characterized the G + C-rich PER3
      element for its ability to bind trans-acting factors. Gel retardation and
      methylation interference (MI) assays show that PER3 binds transcription factor
      Sp1. In addition, an anti-Sp1 antibody recognizes the PER3 DNA-binding protein. A
      3-bp mutation abrogating the capacity of PER3 to bind Sp1 in vitro completely
      abolished expression of the reporter gene construct containing only PER3 and
      PER1, while in a construct containing the first 256 bp of the Prph promoter, it
      led to an 80% decrease with respect to the control wild-type construct. Finally,
      by co-transfection of a Sp1-expressing plasmid, we show that Sp1 can stimulate
      transcription from a reporter gene containing the PER3 sequence. Together, these
      results indicate that interactions between Sp1 and the proteins binding PER1 are
      involved in the control of the Prph gene.

PMID- 7622043
TI  - Promoter regulation of a differentially expressed gene in the human colonic
      epithelial cell lines HT29-18 and HT29-18-C1.
AB  - Gene A4 is transcriptionally activated upon enterocyte differentiation of the
      human colonic epithelial cell line HT29-18 and its highly differentiated subclone
      HT29-18-C1 [Oliva et al., Arch. Biochem. Biophys. 302 (1993) 183-192]. To
      characterize the mechanisms regulating the differential transcription of A4, we
      analyzed its immediate 5'-flanking region for regulatory elements. Promoter
      linked transfection experiments of progressively deleted A4 5'-flanking sequences
      fused to the bacterial cat reporter gene suggest the presence of one negative and
      two positive DNA elements within the first 371 bp of the A4 promoter (pA4). DNase
      I footprint and electrophoretic mobility shift assays demonstrate that one
      positive element which contains the core binding sequence for the transcription
      factor, Sp1, mediates an equal level of transcription in the two cell types. The
      second positive element, localized between nucleotide positions--169 and -152,
      contains a sequence previously unrecognized as a transcription factor-binding
      site. This element mediates a twofold increase in the activity of pA4 in HT29-18
      C1, as compared to HT29-18. Furthermore, nuclear extracts obtained from HT29-18
      C1 contain a higher binding activity for this element than those from HT29-18.
      Southwestern blot analysis suggests that the protein interacting with this
      element has an estimated molecular mass of 50 kDa. We conclude that this protein
      may be involved in the differential regulation of A4 in these intestinal cell
      lines.

PMID- 7622045
TI  - Identification of the cis-elements required for transcriptional control of the
      Chinese hamster ovary APRT gene.
AB  - Transcriptional regulation of the Chinese hamster ovary (CHO) adenine
      phosphoribosyltransferase-encoding gene (APRT) was studied. The 5' region of the
      CHO APRT is G + C-rich, but lacking TATA or CCAAT boxes. RNase protection assays
      indicate that it contains multiple transcription start points (tsp). A tsp 64 bp
      upstream from the translation start codon is denoted as +1. Linker-scanning (LS)
      mutation analysis indicates that the -33 to +19 region is important in regulating
      APRT transcription. Mutations in the -23 to -14 region abolish transcription
      initiated from the -23 downstream region. An unidentified protein complex binds
      to this region. Three Sp1-binding sites are found in the APRT promoter; however,
      mutations of the Sp1-binding sites do not reduce APRT transcription. Mutations at
      two putative GCF-binding sites increase levels of transcription.

PMID- 7622046
TI  - A candidate marsupial PrP gene reveals two domains conserved in mammalian PrP
      proteins.
AB  - The normal function of the pathogenicity-related protein, PrP (or prion protein),
      is unknown. To shed light on functionally important domains, we have
      characterized a candidate marsupial PrP gene. The deduced marsupial PrP has an
      overall identity of about 80% to eutherian PrP at the amino acid (aa) level. This
      similarity is not equally distributed and two regions (aa 118-142 and 177-223)
      are particularly highly conserved. In contrast, a repeat region in the N-terminal
      half of the marsupial PrP shows dipeptide inserts not described in other PrP.
      Another particular feature of the marsupial gene is the lack of a continuous ORF
      on the antisense strand, as is found in most eutherian PrP. We propose that
      antisense ORFs found in other species are artefactual. Comparison with all known
      PrP argues that the molecule characterised is the true marsupial PrP orthologue.

PMID- 7622047
TI  - Cloning and characterisation of an ovine interleukin-10-encoding cDNA.
AB  - Expression of the interleukin 10-encoding (IL-10) mRNA by ovine (ov-) cells, in
      response to mitogenic stimulation, was assessed by Northern blot and polymerase
      chain reaction (PCR) analyses using a human (hu) IL-10 cDNA probe and
      oligodeoxyribonucleotide primers based on homologous regions of the human and
      murine IL-10 cDNA sequences. A 315-bp cDNA generated by the PCR analysis was
      cloned and used to screen a lipopolysaccharide-stimulated alveolar ov-macrophage
      cDNA library. The full-length ov-cDNA sequence isolated translates to a protein
      of 177 amino acids (aa) with a predicted 18-aa leader sequence and molecular mass
      of 20,165 Da. Expression in a mammalian system demonstrated that the ov-cDNA
      encoded a protein with the expected IL-10 biological activity. Both recombinant
      huIL-10 and supernatants from COS cells transfected with an expression vector
      containing the ovIL-10 cDNA inhibited production of IL-1 and tumour necrosis
      factor-alpha by ov-alveolar macrophages. Genomic DNA analysis indicated ovIL-10
      exists as a single gene within the ov-genome.

PMID- 7622048
TI  - The gene encoding bovine pregnancy-associated glycoprotein-1, an inactive member
      of the aspartic proteinase family.
AB  - Bovine pregnancy-associated glycoprotein 1 (bPAG1) is a member of the aspartic
      proteinase family. It becomes detectable in maternal serum soon after
      implantation and is produced specifically in the invasive binucleate cells of the
      placenta. As a result of a key mutation within its catalytic center, bPAG1
      appears to be proteolytically inactive. Its gene consists of nine exons (size
      range 99-281 bp) and eight introns (87-1800 bp) organized in a manner very
      similar to those of proteolytically active mammalian aspartic proteinases. The
      transcription start point (tsp) is located 53 or 54 bp upstream from the start
      codon (ATG) and 19 bp downstream from a 5'-TATATAA sequence. Southern blot
      analyses have indicated the presence of two bPAG1 genes. By screening with an
      antiserum raised against bPAG1, a less common cDNA with 91% sequence identity to
      the bPAG1 transcript has been isolated from a placental cDNA library and
      presumably represents the second gene. At least eight other genes with sequences
      that hybridize relatively weakly to the bPAG1 probe are present in the bovine
      genome. Despite the similarities in the transcribed portion of the genes encoding
      PAG1, pepsinogen and other mammalian aspartic proteinases, the sequences upstream
      from the tsp of bPAG1 are unique.

PMID- 7622049
TI  - Searching for non-V kappa transcripts from the human immunoglobulin kappa locus.
AB  - The 76 V kappa (variable) gene segments of the human immunoglobulin kappa locus
      (Ig kappa) were cloned in two contigs. Within each contig the distances between
      the genes range from a few hundred bp to 31 kb. We have now studied the question
      of whether transcripts are produced from intergenic regions, from regions near
      the kappa locus or from V kappa orphon regions. RNAs from several cell lines were
      converted to cDNAs which were then hybridized to the cosmid and phage lambda
      clones of the locus and of the orphon regions; the conditions were chosen such
      that the hybridization of transcripts with repetitive elements was minimized. The
      expression of a rearranged V kappa gene in a lymphoid cell line was readily
      detected. Also, a region 46 kb downstream from C kappa (constant) and a cDNA
      clone from a non-lymphoid cell line hybridizing to this region were studied in
      some detail. No transcripts were found, however, to be derived from the
      intergenic regions of the germ-line kappa locus which is in keeping with current
      ideas on the evolution of the V kappa multigene family.

PMID- 7622050
TI  - Functional antibody single-chain fragments from the cytoplasm of Escherichia
      coli: influence of thioredoxin reductase (TrxB).
AB  - The cytoplasmic expression of a functional antibody (Ab) fragment, containing the
      correct intradomain disulfide bonds, was investigated in E. coli. We used a
      single-chain Fv (scFv) fragment of the levan-binding Ab ABPC48, which was shown
      to be functional only in the presence of the disulfide bonds. Significant amounts
      of functional, disulfide-containing scFv could be produced in the cytoplasm of E.
      coli in the absence of thioredoxin reductase (TrxB) activity. The amount of
      soluble protein remained largely unchanged by this null mutation. A stronger
      promoter did not result in further improved yields of functional Ab fragment,
      despite much higher protein production, suggesting that inefficient disulfide
      formation was still limiting the yield of active scFv. This method of expressing
      functional Ab fragments in the cytoplasm of E. coli may be important for
      screening and selection systems.

PMID- 7622052
TI  - Cloning and expression analysis of a human cDNA homologous to Xenopus TFIIIA.
AB  - We report here the nucleotide sequence of a clone, C2H2-34.10, isolated from a
      human brain cDNA library using degenerate oligodeoxyribonucleotide hybridization.
      C2H2-34.10 has extensive homology to the Xenopus laevis 5S DNA/RNA-binding
      protein, TFIIIA. The deduced amino acid (aa) sequence of the human clone gives a
      protein of 363 aa with identity to TFIIIA from both X. laevis (57%) and Rana
      pipiens (59%). This human clone contains nine C2H2-type zinc fingers like frog
      TFIIIA. Northern blot analysis indicates that the C2H2-34.10 RNA is expressed in
      human ovary, as well as human neuronal cell lines.

PMID- 7622051
TI  - Structure and function of the HOX A1 human homeobox gene cDNA.
AB  - Homeobox genes code for transcription factors and are arranged in clusters, named
      A, B, C and D, found on four separate chromosomes in vertebrates. They contain a
      homeobox DNA sequence which codes for the homeodomain, a region of amino acids
      responsible for the DNA binding exhibited by these proteins. During embryonic
      development, the homeobox genes are both spatially and temporally regulated. In
      teratocarcinoma cell cultures, homeobox genes are regulated by retinoic acid
      (RA). The cDNAs from the first gene in the human HOX A cluster, HOX A1 (1.6),
      were cloned and the nucleotide sequence of a full-length cDNA was determined. It
      is highly homologous to its murine counterpart. Another HOX A1 cDNA was cloned,
      corresponding to an alternatively spliced form. In vitro translation of the full
      length cDNA clone gave rise to a protein of 36 kDa. In PA-1 human teratocarcinoma
      cells HOX A1 is the earliest HOX A gene to be expressed after treatment with RA.
      To test whether HOX A1 could function as a early regulator of other HOX A cluster
      genes, we cotransfected into PA-1 human teratocarcinoma cells sense and antisense
      HOX A1 cDNAs expressed from an SV40 promoter with a 5.4-kb RA-sensitive HOX A4
      (1.4) promoter-cat reporter. We found no effect of HOX A1 on the HOX A4 promoter.
      However, cotransfection of HOX A5 (1.3) was able to inhibit the HOX A4 promoter
      activity.

PMID- 7622053
TI  - Cloning and structure of the gene encoding the human N-methyl-D-aspartate
      receptor (NMDAR1).
AB  - The complete gene encoding the human N-methyl-D-aspartate receptor subunit NR1
      (NMDAR1) has been isolated on a single cosmid clone. The gene is composed of 21
      exons distributed over a total length of about 31 kb. More than 24 kb were
      sequenced. Exons 4, 20 and 21 are identical in their amino-acid sequence to those
      exons that are subject to alternative splicing in rat, indicating that all eight
      NMDAR1 isoforms found in rat will also be expressed in the human brain. Computer
      analysis of the pre-mRNA sequence revealed no secondary structures stable enough
      to explain alternative splicing. We suggest that cell-specific factors control
      expression of different isoforms. The promoter region contains two perfect copies
      of the recognition sequence for the Drosophila even-skipped protein, indicating
      that the developmentally regulated expression of NMDAR1 is controlled by a
      homeobox protein. The complete cosmid clone covering NMDAR1 was mapped to
      chromosome 9q34.3-qter by fluorescent in situ hybridization (FISH). The telomeric
      location is supported by an imperfect (CA)n repeat homologous to a subtelomeric
      repeat on chromosome 16p.

PMID- 7622054
TI  - Detailed physical mapping of the genes encoding glycophorins A, B and E, as
      revealed by P1 plasmids containing human genomic DNA.
AB  - Human glycophorins A, B and E (GPA, GPB and GPE) are members of the glycophorin
      gene family encompassing a 330-kb genomic segment located on chromosome 4, band
      q31 [Onda et al., J. Biol. Chem., 269 (1994) 13013-13020]. This gene family was
      apparently generated by two successive duplications of an ancestral gene. One of
      the progenitor genes, resulting from the first duplication, directly evolved into
      the GPA gene. The other progenitor gene acquired a unique 3'-region sequence and
      was then duplicated to yield GPB and GPE. In order to obtain a more detailed
      understanding of how these different members of the gene family evolved, we
      isolated several P1 plasmid clones encoding GPA, GPB or GPE. The precise
      locations of exon 1 and the exon encoding the transmembrane (TM) domain in GPA,
      GPB and GPE were then determined by hybridization with specific probes after
      restricted DNA fragments were separated by pulsed-field gel electrophoresis. The
      results obtained showed that the distances between exon 1 and exon 2 are almost
      equal for GPA and GPB, whereas this distance is larger in GPE. In contrast, the
      distance between exon 2 and the exon encoding the TM domain was shown to be the
      same among GPA, GPB and GPE. These results suggest that the gene divergence,
      i.e., insertions or deletions, took place after two successive duplications and
      supports the hypothesis that GPE acquired a portion of the GPA sequence
      surrounding exon 2 by gene conversion.

PMID- 7622055
TI  - The apolipoprotein AICIII-AIV gene cluster: sequence of the ApoCIII-ApoAIV
      intergenic region.
AB  - The genes coding for human apolipoproteins AI, CIII and AIV are tandemly
      organised in a cluster on chromosome 11. The sequence of 4 kb of the 6.6-kb
      ApoCIII-ApoAIV intergenic region was unknown until now. Since different elements
      involved in the transcriptional regulation of the three genes of the cluster were
      previously identified in this region, we decided to sequence it. We present here
      the complete sequence of the region. Its availability will allow study of the
      transcriptional regulation of ApoCIII and ApoAIV at the molecular level. In
      addition, the use of PCR to study the polymorphic sites detected in the ApoCIII
      ApoAIV intergenic region will now be possible. Some of these sites have been
      associated with lipid disorders and coronary heart disease.

PMID- 7622056
TI  - Sequences of apolipoprotein B 3' hypervariable repeat alleles.
AB  - The apolipoprotein B-encoding gene (apoB) 3' end hypervariable repeats contain 11
      to 16-bp A+T-rich sequences and are organized tandemly. Sixteen alleles varying
      in repeat number (26, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55 and
      58) were sequenced. Sequencing revealed a gradual extension of the number of bd
      (5'-TTTTATAATTAAAATA TTTATAATTAAATA) repeats [the fourth and fifth repeat units
      in variable-number tandem repeat 26 (VNTR26)] from alleles 26 to 58. In addition,
      four ef (5'-TTTTATAATTAAAATG TTTATAATTACATA) repeats (the eighth to fifteenth
      repeat units in VNTR26) in alleles 43, 45 and 47, and one ed (5'-TTTTATAATTAAAATG
      TTTATAATTAAATA) repeat (the sixth and seventh repeat units in VNTR26) in alleles
      49, 51, 53 and 55 were deleted. Alleles 43, 45, 47 and alleles 49, 51, 53, 55, 58
      also had variations at the 5' end of this repeat region (the first to third
      repeat units in VNTR26); the 3' end (the 16th to 26th repeat unit of VNTR26) of
      all alleles was invariant. This molecular event indicates a systemic expansion or
      contraction in this region.

PMID- 7622057
TI  - Microbial secretion of biologically active human transforming growth factor alpha
      fused to the Streptomyces protease inhibitor.
AB  - A secretory production system for the active form of transforming growth factor
      alpha (TGF alpha) was established in Streptomyces lividans using a gene encoding
      the secretory protease inhibitor, Streptomyces subtilisin inhibitor (SSI). It was
      demonstrated that deletion of one of the putative dual ssi terminators is
      effective to extracellularly produce a heterologous polypeptide in a fused form.
      The recombinant fusion protein, SSI::TGF alpha, was purified to homogeneity by a
      combination of hydrophobic chromatography and reverse-phase high-performance
      liquid chromatography (RP-HPLC). It was noteworthy that the SSI::TGF alpha hybrid
      protein exhibited bifunctional activity: the TGF alpha activity for cell growth
      promotion and the inhibitory activity of SSI. Taken together with the results of
      analytical gel filtration, these findings strongly indicate that each moiety in
      the fusion protein correctly folds and the whole hybrid molecule exists in a
      dimeric form, which results in its bifunctional activity.

PMID- 7622058
TI  - Cloning, mapping and expression of PEBP2 alpha C, a third gene encoding the
      mammalian Runt domain.
AB  - PEBP2/CBF is a heterodimeric transcription factor composed of alpha and beta
      subunits. Previously, we reported two distinct mouse genes, PEBP2 alpha A and
      PEBP2 alpha B, which encode the alpha subunit. PEBP2 alpha B is the homologue of
      human AML1, encoding the acute myeloid leukemia 1 protein. AML1 and human
      PEBP2/CBF beta were detected independently at the breakpoints of two
      characteristic chromosome translocations observed frequently in two subtypes of
      acute myeloid leukemia. The PEBP2 alpha proteins contain a 128-amino-acid (aa)
      region highly homologous to the Drosophila melanogaster segmentation gene runt.
      The evolutionarily conserved region, named the Runt domain, harbors DNA-binding
      and heterodimerizing activities. In this study, we identified the third Runt
      domain-encoding gene, PEBP2 alpha C, which maps to 1p36.11-p36.13 in the human
      chromosome and encodes a 415-aa protein. PEBP2 alpha C forms a heterodimer with
      PEBP2 beta, binds to the PEBP2 site and transactivates transcription, similar to
      PEBP2 alpha A and PEBP2 alpha B.

PMID- 7622060
TI  - Cloning, sequencing and functional expression of a cDNA encoding a NADP-dependent
      malic enzyme from human liver.
AB  - This work reports the structure of a cDNA (ME) encoding a human malic enzyme (ME)
      (malate NADP oxidoreductase, EC 1.1.1.40) elucidated by joining several
      overlapping fragments amplified by PCR from human hepatic cDNA or from cDNA
      libraries. The full-length cDNA has an open reading frame (ORF) of 1719 bp that
      encodes a 572-amino-acid protein of 64 113 Da, similar to the native monomeric,
      cytosolic, NADP-dependent ME isolated from human liver. The comparison of the
      structure of this cDNA with that of the human mitochondrial NAD(P)-dependent ME
      (EC 1.1.1.39) shows a homology of 63%, suggesting that these two forms originated
      from the same gene. The expression of the cDNA in Escherichia coli as a
      translational fusion (glutathione S-transferase::ME) protein yielded a product of
      the predicted mass. The recombinant protein shows NADP-dependent malate
      oxidoreductase activity and is virtually inactive with NAD. It also shows other
      distinct features of the native cytosolic NADP-dependent ME, like Mn2+
      dependence, similar substrate (Km = 117 microM) and cofactor affinity (Km = 2
      microM) constants, and a lack of allosteric regulation. In human proliferative
      cells, the NADP-dependent ME activity is poorly expressed and barely inducible by
      thyroid hormones.

PMID- 7622059
TI  - Structural organization of the gene encoding the human iron-sulfur subunit of
      succinate dehydrogenase.
AB  - The iron-sulfur protein (Ip) subunit of succinate dehydrogenase (SDH and complex
      II) of the respiratory chain is highly conserved in evolution [Gould et al.,
      Proc. Natl. Acad. Sci. USA 86 (1989) 1934-1938]. We have cloned the entire human
      Ip cDNA, as well as the Ip-encoding gene (SDH-B) from two genomic human
      libraries. The cDNA contains a coding sequence of 840 nt, flanked by a 5'-UTR of
      133 nt and a 3'-UTR of 123 nt. The entire transcript is encoded by eight exons
      within approx. 40 kb. The seven introns range in size from 0.75 kb to > 11 kb,
      and they appear to be of the 'late' intron class. Approx. 5 kb of upstream
      sequence was also cloned, and approx. 2.4 kb of the promoter region were
      sequenced and analyzed for consensus elements binding potential transcription
      factors and transcriptional activators.

PMID- 7622061
TI  - The gene encoding human 2-oxoglutarate dehydrogenase: structural organization and
      mapping to chromosome 7p13-p14.
AB  - Genomic clones covering the entire sequence of the gene encoding human 2
      oxoglutarate dehydrogenase (OGDH) were isolated by screening leukocyte and
      placenta genomic libraries with radio- and digoxigenin (DIG)-labeled human OGDH
      cDNAs. The human OGDH gene contains 22 exons spanning approx. 85 kb. All
      exon/intron splice junctions follow the GT/AG rule. The results of primer
      extension analysis imply that the OGDH transcription start point is a thymine
      residue 55 bp upstream from the ATG start codon. The 5'-flanking region of OGDH
      lacked canonical TATA or CAAT boxes. Using DNAs from human x rodent somatic cell
      hybrids that segregate human chromosomes in conjunction with fluorescence in situ
      hybridization, human OGDH was assigned to chromosome arm 7p, an area that
      corresponds to the boundary between bands 7p13 and 7p14.

PMID- 7622062
TI  - The human PRR2 gene, related to the human poliovirus receptor gene (PVR), is the
      true homolog of the murine MPH gene.
AB  - Until now it was assumed that the murine poliovirus (PV) receptor homolog gene
      (MPH) had been identified. Alternative splicing of MPH transcripts generates two
      glycoproteins named MPH alpha and MPH beta which share an identical N-terminal
      region composed of three immunoglobulin (Ig)-like domains and different C
      terminal regions. Using a degenerate PCR strategy, we describe the identification
      of a second human PVR-related gene (PRR2), which encodes two glycoproteins, PRR2
      alpha (short form) and PRR2 delta (long form). They present 69 and 73% identity
      with MPH alpha and MPH beta, respectively. In contrast, the human PVR protein
      exhibits 51% identity which is moreover restricted to the three Ig domains of the
      murine protein. We therefore propose that PRR2, and not PVR, is the true human
      homolog of MPH. In addition, Northern blot analysis showed that two mRNA isoforms
      of 3.0 kb (PRR2 alpha) and 4.4 kb (PRR2 delta) are ubiquitously found in various
      normal human tissues. In situ hybridization allowed us to map PRR2 to the 19q13.2
      q13.4 bands of the human genome, in the same chromosomal region as PVR.

PMID- 7622063
TI  - Gene assignment by polymerase chain reaction: localization of the human potassium
      channel IsK gene to the Down's syndrome region of chromosome 21q22.1-q22.2.
AB  - Gene mapping, using the polymerase chain reaction (PCR) on DNA obtained from a
      human/rodent hybrid cell line carrying only the human chromosome 21, permitted
      the assignment of the human IsK gene, encoding a slowly activating potassium
      channel, to chromosome 21. PCR analysis of two complete panels of human/rodent
      hybrid DNA mapped IsK to chromosome 21 with 100% concordance. By performing PCR
      on DNA of a human chromosome 21 regional mapping panel the gene was sublocalized
      to chromosome 21q22.1-q22.2, which also contains the putative Down's syndrome
      (trisomy 21) region. The PCR product obtained from the hybrid cell line DNA
      carrying only human chromosome 21 was sequenced, thus confirming that the PCR
      product was derived from human IsK.

PMID- 7622064
TI  - Sequence of the porcine full-length cDNA encoding ribosomal protein rpS12.
AB  - The full-length cDNA encoding the porcine ribosomal protein rpS12 was shown to be
      differentially expressed in endothelial and smooth muscle cells. A cDNA clone
      containing the entire rpS12 sequence was isolated from growth-stimulated
      capillary endothelial cells by use of subtractive hybridization and differential
      screening. The porcine rpS12 cDNA coding region exhibits 94% identity to the rat
      rpS12 and 92% to the human rpS12 cDNAs.

PMID- 7622065
TI  - Sequence analysis of the canine adenovirus 2 fiber-encoding gene.
AB  - The gene coding for the fiber protein (Fip) of canine adenovirus type 2 (CAV-2)
      has been cloned and sequenced. The putative protein has 80% sequence similarity
      with the CAV-1 Fip. The observed differences may contribute to the known
      differences in cell tropism and virulence of the two types of CAV.

PMID- 7622066
TI  - Cloning of the canine interleukin-2-encoding cDNA.
AB  - Here we report the nucleotide sequence of the canine interleukin-2 (IL-2)
      encoding cDNA. Cloning of the canine IL-2 cDNA was achieved by the polymerase
      chain reaction employing, as a template, a cDNA derived from mitogen-stimulated
      canine splenic lymphocyte mRNA. The deduced amino acid (aa) sequence of canine IL
      2 consists of 155 aa and displays 84% sequence similarity to human IL-2.

PMID- 7622067
TI  - Identification of a new member of the human eIF-5A gene family.
AB  - Using an oligodeoxynucleotide generated by rapid PCR amplification of 5'-cDNA
      ends (5'-RACE) as a detection probe, we have isolated a new genomic clone
      encoding the human eukaryotic initiation factor 5A (eIF-5A). Sequence analysis
      revealed that the eIF-5A coding region is identical to the corresponding cDNA but
      interrupted by three introns. In a plasmid shuffle experiment we show functional
      replacement of the essential homologous gene in Saccharomyces cerevisiae by this
      human eIF-5A.

PMID- 7622068
TI  - The human gene encoding the largest subunit of RNA polymerase II.
AB  - The nucleotide sequence of a large portion of the human RNA polymerase II large
      subunit (RpII LS)-encoding gene and its whole gene structure were determined. The
      RpIILS gene consists of 29 exons. The sequence of the 5' flanking region is
      highly conserved as compared with that of the mouse RpIILS and contains several
      SP1-binding sites, a CCAAT sequence and a sequence homologous to a heat-shock
      element. In addition, several inverted repeats and palindrome sequences were
      involved in the 5' upstream region. Those suggest that the 5' flanking domain of
      RpIILS would be highly structured which may be responsible for transcriptional
      regulation.

PMID- 7622069
TI  - Cloning and sequencing of a cDNA encoding a novel member of the human brain
      GABA/noradrenaline neurotransmitter transporter family.
AB  - Screening of a human hippocampal cDNA library with a rat creatine transporter
      cDNA-specific probe revealed two types of clones. One identical to the published
      creatine transporter cDNA sequence (CRT1) and another (CRT2) with four segments
      of oligodeoxyribonucleotide substitution or addition in different sites of the
      CRT1 coding sequence. Translation of the CRT2 coding sequence reveals a new
      protein with regions of perfect homology with the CRT1 amino-acid sequence.

PMID- 7622070
TI  - Genes encoding human serum amyloid A proteins SAA1 and SAA2 are located 18 kb
      apart in opposite transcriptional orientations.
AB  - The three expressed genes of the human serum amyloid A gene family (SAA1, SAA2
      and SAA4) have been isolated in four contiguous clones selected from a chromosome
      11 cosmid library. Analysis of these clones revealed that SAA1 and SAA2 are
      located 18 kb apart in opposite transcriptional orientations, while SAA4 lies 11
      kb downstream from SAA2 in the same orientation: 3'(SAA1)5'-18 kb-5'(SAA2)3'-11
      kb-5'(SAA4)3'. A fifth SAA clone isolated from this library was noncontiguous
      with the other four and contained the SAA3 pseudogene.

PMID- 7622071
TI  - Cloning of the gene encoding human somatostatin receptor 2: sequence analysis of
      the 5'-flanking promoter region.
AB  - Using a cDNA probe, genomic clones were obtained for the 5' flanking promoter
      sequence of the human somatostatin receptor 2-encoding gene (SSTR2). A 3.8-kb
      sequence directly upstream from the start codon was analyzed. This sequence
      shares a number of characteristics with the promoters of other G-protein-coupled
      receptor (GPCR)-encoding genes including a number of G+C-rich regions, binding
      sites for several transcriptional factors, and the absence of coupled TATAA and
      CAAT sequences.

PMID- 7622072
TI  - Cloning and sequence analysis of a cDNA encoding human syntaxin 1A, a polypeptide
      essential for exocytosis.
AB  - A clone encoding human syntaxin 1A was isolated and sequenced from a human brain
      library. The deduced sequence encodes a 288-amino-acid (aa) protein that
      presumably plays a critical role in neurotransmitter exocytosis and is 98.0%
      identical to the aa sequence of rat syntaxin 1A.

PMID- 7622073
TI  - Conjunctival tissue examination in severe eye burns: a study with scanning
      electron microscopy and energy-dispersive X-ray analysis.
AB  - BACKGROUND: Long-lasting inflammation is a major problem in treatment after
      severe eye burns and may find expression in an altered elemental composition of
      the conjunctiva. Particulate contamination of biological tissue induces such
      inflammatory processes. In the anterior eye segment, trauma or subsequent therapy
      may give rise to such contamination. Scanning electron microscopy and energy
      dispersive X-ray analysis are able to detect traumatic residues of submicron size
      and changes of the elemental composition. METHODS: Conjunctival specimens from
      first-time peridectomy of three healthy and nine severely burnt-eyes were
      examined with scanning electron microscopy and energy-dispersive X-ray analysis.
      The samples were prepared as cryo- or paraffin sections, mounted on carbon blocks
      and coated with evaporated elemental carbon. RESULTS: The samples of healthy
      conjunctiva showed higher concentrations of Na, P and CI. These elements showed
      lower concentrations in conjunctival stroma of burnt eyes excised before the 20th
      day after trauma than in material obtained subsequently. In two burnt
      conjunctival specimens there was severe traumatic contamination with Ca in
      Ca(OH)2 and CaO burns, and in one case the traumatic substance was Si, in a
      peroxide plus silicone spray burn. In the remaining six cases, particulate
      contamination with Fe, Al, Ni, Zn, Cu, Ti and other substances was present in the
      burnt conjunctivas, while no contamination was detected in the specimens of
      healthy conjunctivas. CONCLUSIONS: The origin of the contaminant particles is
      assumed to be the trauma itself and the subsequent therapy. These investigations
      stress the importance, for clinical purposes, or early peridectomy and
      contamination-free therapy.

PMID- 7622074
TI  - Quantitative assessment of lateral interaction as determined by computerized
      quantitative layer-by-layer perimetry.
AB  - BACKGROUND: Quantitative layer-by-layer perimetry is a psychophysical technique
      which assesses lateral interaction in human vision. In prior designs of this
      technique the test procedure was time-consuming and quantitative assessment of
      the results was not possible. In order to shorten test duration and provide
      quantitative experimental data, a new computerized version of the technique has
      recently been developed. METHODS: A mathematical model for describing lateral
      interaction as assessed by computerized quantitative layer-by-layer perimetry was
      developed, and experimental data from the testing of 18 normal persons were
      fitted to the model. Two descriptive parameters of, respectively, lateral
      stimulation and lateral inhibition were for each test point related to the
      differential light sensitivity and to the eccentricity in the visual field.
      RESULTS: The two parameters describing lateral stimulation could not be reliably
      estimated. However, the two parameters describing lateral inhibition showed,
      respectively, a positive correlation with the differential light sensitivity in
      the visual field and a significant decline with increasing eccentricity in the
      visual field. CONCLUSION: The technique and the mathematical model employed are
      suitable for quantitative assessment of lateral inhibition in human vision.

PMID- 7622075
TI  - Association of intermediate uveitis with HLA-A28: definition of a new systemic
      syndrome?
AB  - BACKGROUND: Endogenous posterior uveitis (PU) can be associated with systemic
      diseases, and certain forms have strong association with HLA antigens. Much less
      is known regarding intermediate uveitis (IU). The purpose of this study was to
      determine whether IU is associated with the HLA system and whether it can be
      associated with systemic symptoms. METHODS: In 179 consecutive patients
      consulting for uveitis, a detailed history was obtained and a physical
      examination performed. HLA typing for 71 HLA-A, B, DR and DQ antigens, laboratory
      tests, and radiography of the chest, sinuses, and sacroiliac joints were
      systematically performed. RESULTS: Thirty-two patients (18%) had IU; 51 (28.5%)
      had PU and constituted our internal control group. Nine of the patients with IU
      (28%) had the HLA-A28 antigen, compared with 8.1% of a healthy control population
      and 8.6% of the patients with PU (P < 0.001). An associated disease was found in
      four patients with IU (12.5%) (none was HLA-A28) and in 45% of the patients with
      PU (P < 0.01). Some 67% of HLA-A28 patients with IU had arthralgias affecting the
      knee(s), compared with 17% of non-HLA-A28 patients and 18% of patients with PU (P
      < 0.05 and P < 0.01 respectively); 55% had gonalgias and hypocomplementemia
      compared with 9% and 2% respectively (P < 0.01 and P < 0.001). CONCLUSIONS: IU is
      significantly associated with HLA-A28; patients having this antigen may represent
      a subset of the disease characterized by an increased prevalence of arthralgias
      and hypocomplementemia.

PMID- 7622076
TI  - Retinitis pigmentosa and the question of photoreceptor connecting cilium defects.
AB  - BACKGROUND: A generalized structural defect of the cilia in various tissues,
      including photoreceptor connecting cilium, has been postulated as occurring in
      some forms of retinitis pigmentosa (RP). However, the literature on ciliary
      abnormalities in RP contains contradictory findings. METHODS: In this study the
      fine structure of photoreceptors from 17 RP donors including X-linked RP, X
      linked RP carrier state, autosomal dominant RP and autosomal recessive RP was
      examined by electron microscopy. RESULTS: Photoreceptor preservation was commonly
      observed even in the most advanced cases of the disease, especially in the
      perimacular area, in the proximity of the optic nerve and in the periphery.
      Primary ciliary defects, expressed as additional or missing microtubules, were
      found in none of the samples. Comparison of photoreceptors in normal and RP
      retinae showed thinner cilia in RP cells but no defect in the microtubule
      arrangements within the connecting cilium. CONCLUSION: Additional or missing
      microtubules in ciliated cells are not uncommon and have been reported in the
      literature and recorded in some studies of RP tissue. Such defects, however, are
      believed to be acquired rather than inherited abnormalities of cilia and were not
      observed in the photoreceptor connecting cilia of RP patients examined in this
      study. Thinning of the cilium may also be a secondary effect related to cell
      shrinkage early during apoptosis, which is postulated to be a common pathway in
      photoreceptor degeneration.

PMID- 7622077
TI  - Limits of two-dimensional planimetry in the follow-up of glaucomatous optic
      discs.
AB  - BACKGROUND: To test the intra-observer, intra-photographic variability of two
      dimensional measurements of the optic nerve head we used computer-assisted
      planimetry. Depending on the variability, we calculated the confidence intervals
      of the optic disc parameters which could be indicative of glaucomatous damage on
      follow-up. METHODS: Slides of the optic disc were taken from 10 eyes of 10
      patients (n = 6 open angle glaucoma, n = 4 ocular hypertension) using a Zeiss
      fundus camera. All eyes were evaluated 10 times within a random sequence on 10
      different days. We obtained the absolute values of the disc radii and the cup
      radii in steps of 1, 10, and 45 deg in predefined quadrants and the mean radii.
      RESULTS: The confidence interval of the cup radius on follow-up, depending on
      sector size, ranged between 62 and 38% for small cups (radius 0.2 mm) and between
      12 and 7% for large cups (radius 0.8 mm). The confidence intervals of the
      cup/disc ratio distinguishable from the disc boundary, depending on sector size,
      ranged between 0.81 and 0.89 for small discs (radius 0.5 mm) and from 0.90 to
      0.94 for large discs (radius 1.0 mm). The confidence intervals of the cup/disc
      ratio indicating an increase on the cup radius in follow-up, distinguishable from
      the boundary of the disc, ranged, depending on sector size, between 0.57 and 0.75
      for small discs (radius 0.5 mm) and from 0.81 to 0.89 for large discs (radius 1.0
      mm). CONCLUSION: The smaller the disc, the more difficult is the detection of
      glaucomatous damage, and the larger the cup, the more difficult is the detection
      of progression of glaucomatous damage.

PMID- 7622079
TI  - Steps to optimize transscleral photocoagulation.
AB  - BACKGROUND: In transscleral photocoagulation, the desired effect is coagulation
      of parts of the ciliary body or of the peripheral retina. However, the
      application is often limited by the unwanted effect of coagulation of the sclera.
      To reduce this effect, the ratio of incident radiation flux to radiation flux
      transported through the sclera (and able to coagulate the target tissue) should
      be minimized by the incident beam characteristics. METHODS: Monte Carlo
      simulations for the radiation transport problem of multiple scattering in the
      sclera were used to calculate the ratio of transported to incident radiation for
      different parameter settings of beam diameters, optical thicknesses of the sclera
      and beam angles. To verify the theoretical calculations, an simple optical device
      utilizing a bulb instead of a laser source was constructed and applied to
      enucleated porcine eyes. RESULTS: The theoretical calculations showed that the
      ratio of incident to transported radiation flux can typically be decreased by a
      factor of three by increasing the beam radius from 0.35 mm (as used in state-of
      the-art laser devices) to 2 mm. This was confirmed by the experiments.
      Coagulations of the ciliary body or of the peripheral retina were possible with
      power densities an order of magnitude below the values normally applied with
      laser sources. CONCLUSION: To improve transscleral photocoagulation, beam
      diameters should be increased.

PMID- 7622078
TI  - Integrins in human anterior chamber angle.
AB  - BACKGROUND: Integrins, which are composed of an alpha and beta subunit, are
      capable of binding to a number of extracellular matrix proteins and, hence,
      affect cell adhesion and proliferation. METHODS: The distribution of the integrin
      beta (beta 1, beta 3-beta 5) and alpha (alpha 1-6 and alpha v) subunits in human
      anterior chamber angle was studied in eyes from subjects aged 9 months to 81
      years using the indirect immunofluorescence technique. RESULTS: Immunoreaction
      for the beta 1 subunit was found throughout the trabecular meshwork (TM), in the
      cribriform layer, and in the endothelial lining of Schlemm's canal (SC).
      Labelling for the alpha 3 subunit was found in the TM and the cribriform layer
      only. In infant eyes the alpha 5 subunit was present in all three areas with the
      highest concentration in the cribriform layer, whereas no reaction was observed
      in adult eyes. The alpha 6 subunit was localized to the endothelium of SC only.
      Immunoreaction for the alpha v subunit was present in the TM and the cribriform
      layer of infants and young adults. CONCLUSION: The present results suggest the
      presence of several integrin heterodimers, acting as potential receptors for
      laminin, collagen, fibronectin, and vitronectin, in the anterior chamber angle.

PMID- 7622080
TI  - Effect of citicoline on visual acuity in amblyopia: preliminary results.
AB  - BACKGROUND: Citicoline has been used to improve consciousness levels in cerebral
      trauma and as a complement for levodopa in Parkinson's disease. It has also been
      shown that severe glaucomatous visual field deficits improve for at least 4
      months with the use of citicoline. In this paper, preliminary results are
      presented of an open and a double-blind study on the effect of citicoline in
      amblyopia. METHODS: The open study was started in 1991. Fifty patients with
      amblyopia were treated with citicoline (1000 mg i.m. daily for 15 days). They
      were selected from an age group beyond the plastic period of the visual system.
      Occlusion or other types of anti-amblyopic treatment were never used at the same
      time as citicoline. A double-blind study was conducted on 10 more patients,
      randomly assigned to a treatment or placebo group and followed for 6 months. A
      statistical test for repeated measures was performed on all the results. RESULTS:
      A statistically significant improvement in visual acuity was found both for the
      amblyopic and the sound eye in 46 of the 50 patients (92%). The behaviour was
      different for normal and amblyopic eyes. The improvement remained stable for at
      least 4 months. These results have been substantiated by the double-blind study.
      No side effects were observed. CONCLUSION: Citicoline improves visual acuity, at
      least temporarily, in amblyopic patients beyond the plastic period of the visual
      system. Our results suggest that trials of citicoline as a medical treatment of
      amblyopia are warranted.

PMID- 7622082
TI  - Once and future SHMOs.

PMID- 7622081
TI  - A response to representatives from the social HMOs regarding program evaluation.

PMID- 7622083
TI  - Stress, alcohol use, and depressive symptoms in later life.
AB  - The purpose of this study is to use social identity theory in order to evaluate
      whether alcohol use buffers the effects of stress on depressive symptoms. Two
      hypotheses are developed from this perspective. The first specifies that alcohol
      use should reduce the negative impact of events arising in social roles that are
      not valued highly by study participants. The second predicts that alcoholic
      consumption will exacerbate the effects of stressors that emerge in roles that
      are highly salient. Support for these propositions was obtained with data
      provided by a recent nationwide survey of older adults.

PMID- 7622084
TI  - Division of household labor and the well-being of retirement-aged wives.
AB  - A model specifying that certain subjective beliefs and structural conditions
      affect the symbolic meaning wives give to their household labor divisions was
      tested on 144 retirement-age married women. Results indicate that perceptions of
      spousal support mediate the relationship between a couple's division of household
      labor and the wife's well-being. Wives perceive less spousal support when
      housework divisions are more unequal favoring husbands. Lack of spousal support
      in turn leads to wives' lower marital happiness and increased depression. This
      relationship is stronger for employed wives than homemakers, but is not
      diminished either by a wife's traditionalism or by her husband's employment.

PMID- 7622085
TI  - Ethnic trends in survival curves and mortality.
AB  - The nature of secular trends in survival curves has been widely debated. Fries
      (1984) has argued for increasing rectangularization, while Myers and Manton
      (1984a; 1984b) have observed increases in mean age at death with little or no
      change in standard deviation--arguing against rectangularization. We hypothesize
      that ethnic differences in mortality trends may shed light on this argument.
      Using California population data for 1970, 1980, and 1990, we examined ethnic
      differences in rectangularization using both visual and means and standard
      deviations analyses. The resulting patterns varied by ethnicity, gender, and type
      of analyses. Nearly all female groups demonstrated modest rectangularization,
      regardless of mean age of death, while most of the male groups did not.

PMID- 7622086
TI  - Data sources for aging research on racial and ethnic groups.
AB  - This article reports the results of a survey of recent and ongoing aging-related
      data sources supported by U.S. federal agencies. The survey sought to obtain data
      on the sample sizes and topics covered within the data sets maintained and
      frequently used by the various federal agencies engaged in data collection and/or
      analysis. The objective of the study was to determine the suitability of these
      data sets to conduct research on minority elders. Formal tests of the adequacy of
      data set sample sizes to support analysis on various minority groups were
      performed. Each data set was found to be large enough to conduct research on
      white elders, and a majority of the data sets were large enough for research on
      African American elders. However, Hispanics, American Indians, Alaska Natives,
      Asian Americans, and Pacific Islanders were rarely included in sufficient
      numbers.

PMID- 7622087
TI  - Eldercare and work-role conflict: toward an understanding of gender differences
      in caregiver burden.
AB  - This study investigated gender differences in caregiving tasks, role strains, and
      resources to account for gender variations in burden among a probability sample
      of employed, nonspousal caregivers (N = 413). Females were more likely to assist
      with care provision tasks, to report work role strains, and to experience higher
      levels of burden than males. After controlling for known sociodemographic
      dissimilarities in predicting burden, the effect of gender decreased at each step
      when caregiver tasks, work role strains, and resources were entered into the
      regression equation. Results suggest that these differences may partially explain
      the greater negative impact experienced by nonspousal, female caregivers.

PMID- 7622088
TI  - The PACE evaluation: initial findings.
AB  - As of mid-1994 there were nine replications of the On Lok model operating under
      dual capitation payments as sites in the Program of All-inclusive Care for the
      Elderly (PACE). A tenth site had begun operating under capitation, but was unable
      to remain viable. The present descriptive study documents the growth and
      development of the first seven of these sites, all that had been operating under
      capitation during 1992. Comparisons among these sites and with On Lok are
      presented in the areas of organizational structure, client characteristics,
      approaches to case management, service delivery options, and financing. There is
      considerable variability in the implementation of the PACE model. Combined
      Medicare and Medicaid capitation monthly payments range from $2,147 to $5,973.
      These seven PACE sites (excluding On Lok) served a total of 888 current clients
      at the end of 1992, after a cumulative 136 months of experience under capitation.
      The very slow enrollment rates may imply that the target clients are less
      enthusiastic about this model than are its architects. The client selection
      process may suggest niche-marketing or skimming, but not the full representation
      of the nursing home population in their states. Given both the slow enrollment
      and the niche-marketing (the benevolent term) or skimming (the pejorative term)
      that has occurred, caution about the long-term viability of the PACE model may be
      warranted.

PMID- 7622089
TI  - Vision in Alzheimer's disease.
AB  - In order to assess vision in Alzheimer's disease (AD) and related disorders,
      gerontologists must use tests that make minimal cognitive demands on the subject.
      Using such tests, we have found a pattern of deficits in color discrimination,
      stereoacuity, contrast sensitivity, and backward masking that differs from that
      seen in healthy elderly individuals. Impaired vision predicts deficient
      performance of subjects with AD on numerous tests of cognition, underscoring the
      importance of understanding visual changes in this population.

PMID- 7622090
TI  - Relationships among age, exercise, health, and cognitive function in a British
      sample.
AB  - This study was designed to evaluate the association of age, self-rated health,
      and walking activity with four measures of cognitive functioning in 6,979 men and
      women (age range: 18-94 years) randomly selected from British electoral
      registers. Assessments included a face-to-face interview regarding health and
      health beliefs as well as cognitive testing (including simple reaction time [SRT]
      and choice reaction time [CRT]. Hierarchical regression analyses indicated that
      faster reaction time (RT) speed was associated with both younger age and better
      self-rated health. There were also significant interactions of Age by Self-Rated
      Health and of Health Rating by Walking Activity for CRT, as well as an
      interaction of Age by Walking Activity for both SRT and CRT. Exercise and health
      may have an interactive effect on RT speed, and both exercise and health may
      modify age-related changes in RT.

PMID- 7622091
TI  - "To grandmother's house we go": health and school adjustment of children raised
      solely by grandparents.
AB  - This study uses data from the 1988 National Children's Health Supplement (N =
      17,110) to the National Health Interview Survey to examine the health and school
      adjustment of children raised solely by grandparents. We find that these children
      fare quite well relative to children in families with one biological parent
      present, a category which includes both single-parent and blended families.
      Furthermore, children raised solely by grandparents are not significantly
      different, except for academic performance, from children raised in traditional
      families where two biological parents are present.

PMID- 7622092
TI  - Recruiting from the community: lessons learned from the diabetes care for older
      adults project.
AB  - Recruitment methods for enrolling community-based older adults into a study of
      intensive diabetes management are presented. Analysis of a three-step enrollment
      procedure revealed that persons who declined at the first step were slightly
      older and lived farther away from the study site than persons who continued in
      the enrollment process. Persons who declined cited distance from clinic, some
      aspect of the study protocol, or health/personal problems as major barriers to
      involvement. Recruitment strategies were compared, revealing that press releases
      and newspaper advertisements were the most effective strategies for recruiting
      eligible participants. Methods such as those described here should help to
      facilitate future recruitment efforts with community-based older adults.

PMID- 7622093
TI  - Quality of life, values, and teamwork in geriatric care: do we communicate what
      we mean?
AB  - Two major forces are changing the shape of health care for the frail elderly with
      disabling conditions: increasing emphasis on quality of life and growing reliance
      on an interprofessional team-based approach to care. This article outlines a
      conceptual framework for organizing discussions of quality of life for elderly
      persons with disabilities, reviews relevant empirical research, and develops a
      framework for understanding the different dimensions and interpretations of this
      concept--particularly as it is used in communication among health care providers,
      and between them and their elderly patients and families. New models of health
      care to enhance the focus on life quality and collaborative team practice are
      summarized. Proposed is the development of an "empowering and reflective ethic"
      to achieve more effective communication about quality of life in geriatric
      clinical practice.

PMID- 7622094
TI  - Speaking of difficult choices: the creation of a drama and dialogue group on end
      of-life choices.
AB  - The purpose of this project is to relieve the emotional isolation of elders
      concerned about the manner in which they will die, particularly fears about loss
      of control. A counselor engaged elders in dialogue exploring nonthreatening ways
      this could be done. Drama that includes dialogue with the audience was chosen,
      developed, and performed at their retirement facility and in the wider community.
      Elders who attend these performances express gratitude and relief at learning
      they are not alone in their concerns, and for the information about current laws
      and resources for support.

PMID- 7622095
TI  - Reaction reading: a tool for providing fantasy imagery for long-term care
      facility residents.
AB  - Reaction reading, the choral reading of poetry in small groups, gives mentally
      alert long-term care residents an opportunity to react to poetry with knowledge,
      opinion, emotion, and imagination. The activity can be led by a nonprofessional.
      Residents are encouraged to share their reflective fantasy (memory of past places
      and events) and projective fantasy (ideas of places beyond the contemporary
      setting) as inspired by poetic images. Application of the reaction reading method
      and its benefits are described.

PMID- 7622096
TI  - European Helicobacter pylori study group. VIIIth International Workshop on Gastro
      duodenal Pathology and Helicobacter pylori. Edinburgh, Scotland, 7-9 July 1995.
      Abstracts.

PMID- 7622097
TI  - Flow cytometry as a prognostic factor in endometrial cancer--what does it add?

PMID- 7622098
TI  - Prognostic value of DNA ploidy and S-phase fraction in stage I endometrial
      carcinoma.
AB  - Both nuclear DNA content and S-phase fraction (SPF) can be helpful in predicting
      prognosis in certain malignancies. We investigated in a retrospective study the
      prognostic significance of nuclear DNA content and SPF as measured by flow
      cytometry of tumor specimens from 162 women with nonpretreated surgically staged
      FIGO stage I endometrial cancer using clearly defined inclusion criteria. A total
      of 139 (86%) cases were found to be diploid, whereas 23 (14%) were aneuploid.
      Ploidy showed a correlation with histologic grade, estrogen as well as
      progesterone receptor levels, and depth of myometrial infiltration. Univariate
      analysis of follow-up data showed an increased relative risk (RR) for recurrence
      free survival (RFS) for grade 3 tumors (RR = 2.11, ns), for age (RR = 1.04, P =
      0.023) as a continuous variable, and for SPF in diploid tumors (RR = 3.10, P =
      0.035). In addition, univariate analysis of overall survival revealed similar
      results with a slightly increased relative risk for ploidy (RR = 1.52, ns).
      Multivariate analysis of RFS showed age as the only independent prognostic
      factor. Multivariate analysis of RFS for diploid tumors showed no independently
      significant factor; however, age as a continuous variable with a relative risk of
      1.04 and SPF with a relative risk of 2.94 were of borderline significance. Our
      results suggest that abnormalities of the nuclear DNA content and SPF in this
      homogeneous group of patients are associated with clinical and morphological
      prognosticators; however, ploidy is no independent prognostic factor for RFS. For
      diploid tumors, SPF might be a possible independent prognostic factor.

PMID- 7622099
TI  - New gynecologic cancer staging.

PMID- 7622100
TI  - Contracting for professional service agreements.
AB  - A review of several professional service agreements (PSA) of managed care
      organizations which contract with gynecologic oncologists in the Southern
      California area demonstrates several distinct patterns of practice restrictions
      and financial benefits which can help guide the physician who is considering
      signing such an agreement. These contracts must be evaluated in a manner similar
      to any business transaction as they are legally binding and can enhance or
      adversely impact one's clinical practice. Their advantages include increased
      numbers of referrals resulting in higher practice income; however, their
      disadvantages include practice restrictions which can adversely impact office
      overhead, practice efficiency, and the ability to deliver quality medical care.
      General guidelines to physicians evaluating a PSA include (1) avoiding "hold
      harmless" clauses, (2) avoiding contracts which tie enrollment in one plan to
      others, (3) the need to enter any verbal agreements by managed care
      administrators into the contract language, and (4) avoidance of actions which
      might be construed as being in violation of antitrust activities. Furthermore,
      physicians must avoid contracts which will result in the uncontrolled growth of a
      practice beyond its capabilities for expansion.

PMID- 7622101
TI  - Cell biological markers of drug resistance in ovarian carcinoma.
AB  - The aim of the study is to review the mechanisms of resistance to four classes of
      drugs that are widely used in ovarian carcinoma: platinum (cisplatin/carboplatin)
      compounds, classical alkylating agents (cyclophosphamide/melphalan), natural
      drugs (doxorubicin), and "new drugs" (taxol and taxotere). Both platinum and
      classical alkylating agents mediate their cytotoxicity by the formation of drug
      DNA adducts, resulting in DNA damage. Therefore, drug resistance mechanisms are
      (in part) comparable. In ovarian carcinoma cell lines increased repair of DNA
      damage and increased detoxification by binding of drugs to glutathione, possibly
      catalyzed by glutathione S-transferases, have been identified as the most
      prominent resistance mechanisms to these drugs. Studies on the role of DNA repair
      mechanisms and glutathione in human ovarian carcinoma are hampered by the
      complexity of enzyme systems involved in DNA repair and intratumor heterogeneity
      for glutathione. Resistance to doxorubicin appears to be mediated by enhanced
      efflux from the cell by increased expression of membrane glycoproteins acting as
      a drug efflux pump, such as P-glycoprotein. Resistance to doxorubicin can also be
      due to quantitative and/or qualitative changes in the nuclear target of
      doxorubicin, topisomerase (Topo) II. Finally, resistance to taxol may be mediated
      by enhanced expression of P-glycoprotein, while presumed other mechanisms such as
      alterations in tubulin structure, the cellular "target" of taxol, and changes in
      polymerization of tubulin are still largely unresolved. Several ways to modulate
      the reviewed resistance mechanisms are also described. In conclusion, this review
      shows that many cell biological factors may be involved in drug resistance. The
      relevance of the identification of most of these factors in ovarian carcinoma
      patients however remains to be established.

PMID- 7622102
TI  - Simultaneous detection by consensus multiplex PCR of high- and low-risk and other
      types of human papilloma virus in clinical samples.
AB  - A consensus multiplex PCR (CM-PCR) technique was developed to detect high-risk
      (HPV 16/18), low-risk (HPV 6/11), and over 40 other types of human papillomavirus
      (HPV), separately but simultaneously, by mixing three pairs of consensus primers
      in the same PCR mixture, for gene amplification. Simultaneous detection of three
      groups of HPV DNA provides valuable information for clinical practice and this
      procedure is simple and convenient for routine laboratory examinations. We
      detected HPV DNA sequences in plasmid HPV DNA and DNA extracted from tissues of
      condyloma acuminata and cervical carcinoma and from exfoliated cells of the lower
      genital tract of healthy Chinese women living in the People's Republic of China.
      We confirmed that this simple, convenient, and cost-beneficial CM-PCR technique
      is reliable for the detection of HPV DNA sequences.

PMID- 7622103
TI  - Staging laparotomy for endometrial carcinoma: assessment of retroperitoneal lymph
      nodes.
AB  - The surgical staging scheme for uterine corpus cancer adopted in 1988 by the
      International Federation of Gynecology and Obstetrics assigns patients with tumor
      spread to retroperitoneal lymph nodes to stage IIIC. However, a recommended
      approach to the detection of lymph node metastasis is not delineated. As part of
      an ongoing project to assess the value of surgical staging procedures, we
      reviewed the techniques of lymph node evaluation in 295 at-risk patients. Cases
      included clinical stage I patients whose preoperative biopsies demonstrated grade
      2 or 3 adenocarcinoma or papillary serous, clear cell, or mixed carcinoma. We
      arbitrarily divided the retroperitoneal space into 10 lymphatic zones: left and
      right para-aortic, common iliac, external iliac, hypogastric, and obturator.
      Eighty-two percent of patients had some type of node sampling that involved a
      mean of three zones. Thirty-three of 244 sampled cases (13.5%) had nodal
      metastases: 20 had gross involvement and 13 had microscopic. We stratified
      patients into three groups: (1) those who had no node sampling (n = 51), (2)
      those with some nodes biopsied (n = 193), and (3) those whose node sampling
      included a minimum of one para-aortic plus at least one right and left pelvic
      specimen (n = 51). Retroperitoneal recurrences thought to originate from lymph
      node sites were identified for the "node-negative" patients in each group: Group
      1, 4/51 (8%); Group 2, 9/173 (5%); and Group 3, 0/38 (0%). Lymphatic site
      failures were seen in 8 of 33 (24%) patients with biopsy-proven metastases. We
      found that failure to systematically sample pelvic and para-aortic nodes results
      in a small, but real, risk of undetected extrauterine metastasis. A selective
      approach to sampling that includes biopsy from both para-aortic and bilateral
      pelvic lymphatic zones appears to provide an accurate estimate of true node
      negativity. Further evaluation of this approach is warranted.

PMID- 7622104
TI  - Blastocysts exhibit preferential uptake of DNA fragments from the E6-E7 conserved
      region of the human papillomavirus.
AB  - The objective of the study was to determine if embryos at the blastocyst stage
      differentially took up exogenous human papillomavirus (HPV) DNA derived from the
      different HPV types and to determine whether the capture process was active or
      passive. In vivo fertilized mouse embryos were cultured to the blastocyst stage
      in vitro. The mouse blastocysts were incubated for 2 hr in the presence of a
      mixture of exogenous DNA fragments derived from HPV types 6b, 11, 16, and 18. The
      blastocysts were rigorously washed and analyzed for differential uptake of HPV
      gene sequences using the polymerase chain reaction (PCR) and polyacrylamide gel
      electrophoresis. PCR analysis detected HPV type 18 in only 40% of the blastocyst
      groups while detecting the other HPV types in 100% of the blastocysts. The
      negative control group did not show HPV DNA after PCR ruling out possible PCR
      artifacts. Formalin-fixed blastocysts also showed uptake of HPV DNA. In
      conclusion, the data suggest a role for embryos as passive vectors for foreign
      DNA and that the degree of DNA uptake varies with different types of HPV DNA.

PMID- 7622105
TI  - Endometrial carcinoma in elderly women.
AB  - Endometrial carcinoma remains the most common invasive gynecologic malignancy.
      Increased longevity is associated with an increased incidence of endometrial
      carcinoma (EC) in elderly women. While recent studies have looked at aging and
      its relation to ovarian, breast, and cervical cancer, few have focused on EC in
      the growing elderly population. This study analyzed 35 histologic specimens of EC
      in women 75-92 years of age. Findings revealed that only 23% of the tumors were
      Stage I, G1. The majority (77%) were deeply invasive or of advanced stage (IC
      IV). These were G2, G3, or "virulent" types of nonendometrioid EC
      (undifferentiated, clear cell, uterine serous papillary, and squamous cell
      carcinoma). Fifty-seven percent of tumors were endometrioid, of which 9% were
      mixed, including a rare case of nongestational choriocarcinoma. The
      nonendometrioid tumors, compared to the endometrioid types, were more often high
      stage tumors with vascular invasion. They were also more often associated with
      atrophic (vs hyperplastic) uninvolved endometrium. Clinical risk factors
      (nulliparity, obesity, estrogen replacement therapy) were assessed and correlated
      with the histologic findings. It was shown that tumors in the elderly were less
      likely to be estrogen-related. It was concluded that EC in this age group is more
      aggressive, histologically less differentiated, and often nonendometrioid
      compared with EC in the general population. The increased virulence of EC in the
      elderly may be related to the tumor's independence from hormonal factors, to the
      poorly understood but well-known diminished immunologic defense against cancer in
      general in elderly patients, and/or to the belated diagnosis of the disease in
      this population.

PMID- 7622106
TI  - Pelvic exenteration for primary and recurrent vulvar cancer.
AB  - Twenty-one patients who underwent pelvic exenteration for primary (n = 8) or
      recurrent (n = 13) vulvar malignancy at the M. D. Anderson Cancer Center between
      1956 and 1989 were evaluated. A posterior exenteration was performed in 12
      patients, anterior exenteration was performed in 6, and total exenteration was
      performed in 3. In patients with primary tumors, radical vulvectomy and inguinal
      lymphadenectomy were also performed. The median patient age was 57 years. The
      mean tumor diameters were 5 cm (primary) and 4 cm (recurrent). Infections were
      the most frequent postoperative complications (n = 15), followed by pulmonary (n
      = 4) and cardiac problems (n = 3). There were no treatment-related deaths. Five
      patients required further surgery to correct late postoperative sequelae. Four of
      eight patients experienced recurrence after treatment of their primary tumor; the
      recurrences were local only (n = 1), in the inguinal area (n = 2), or local and
      in the pelvis (n = 1). Nine of the 13 patients treated for recurrent tumors
      developed a second recurrence; the second recurrences were all within the pelvis,
      although two also had a distant component. The 5-year survival rates were 70% for
      patients treated for primary disease and 38% for patients treated for recurrent
      disease. Pelvic exenteration is indicated for selected patients with advanced
      vulvar malignancy.

PMID- 7622107
TI  - Observer agreement on interpreting colposcopic images of CIN.
AB  - The purpose of this work was to study intraobserver and interobserver variation
      in the interpretation of colposcopic images of cervical intraepithelial neoplasia
      (CIN). Twenty-three experienced colposcopists were asked to assess colposcopic
      images presented on slides and to select the biopsy site. Eleven cases were
      independently interpreted twice with an interval of 2-3 months by all observers.
      No information about the cytological classification was available. In each case
      the "majority assessment" was considered as the standard, being "no CIN" in 2
      cases, CIN I in 4 cases, CIN II in 3 cases, and CIN III in 2 cases. Intraobserver
      concordance was 66.7%, the kappa value was 0.54. Interobserver agreement was
      found to be 52.4 and 51.0% in the first and second sessions, respectively, while
      the mean kappa values were 0.41 and 0.33, respectively. In selecting the site for
      biopsy, 77.4% of all observers agreed while the same site was selected in 85.3%
      of cases by the individual colposcopist in the two sessions. Overall, CIN I and
      II interpretations revealed lower levels of agreement than no CIN or CIN III
      interpretations. It is concluded that observer variability in interpreting
      colposcopic images and selecting the site for biopsy is in the same range as
      observer variation in other subjective diagnostic tests such as cytology and
      histopathology. This variation should be taken into account in the colposcopical
      management of patients with abnormal cytology.

PMID- 7622109
TI  - Declining use of radiotherapy for invasive cervical cancer in Connecticut: 1983
      1990.
AB  - Data on the use of radiotherapy (i.e., external irradiation and/or intracavitary
      radioactive implants) in the first course of treatment were examined for all 1286
      invasive cervical cancer cases diagnosed between 1983 and 1990 among Connecticut
      residents. These data, from a population-based cancer registry, reflect actual
      treatment practices in the geographic area under study. Use of radiotherapy
      declined from 62% in 1983 to 43% in 1990 (trend test P < 0.001); for "local"
      stage cancers, the decline was from 50% in 1983 to 27% in 1990 (P < 0.001).
      Surveys are needed on physicians' attitudes and decisions regarding alternative
      treatments for cervical cancer.

PMID- 7622108
TI  - The major E6/E7 transcript of HPV-16 in exfoliated cells from cervical neoplasia
      patients.
AB  - HPV-16 is implicated in the development of progressive cervical neoplasia, and E6
      and E7 proteins of this virus play important roles in its oncogenic activity.
      Reverse transcriptase-nested-polymerase chain reaction (RT-nested PCR) method was
      applied to detect the major transcript (E6*I/E7) from E6/E7 ORFs of HPV-16 in the
      exfoliated cervical and vaginal cells from cervical neoplasia patients. The
      incidence of the E6*I/E7 transcript was proportional to the class of cytologic
      diagnosis. Further analysis revealed that the incidence of the E6*I/E7 transcript
      in Pap smears of class I or II was 5/28 (18%) patients who had previously been
      diagnosed as having cervical neoplasia but was 1/37 (3%) patients who had never
      been diagnosed (P < 0.05). These findings suggest that some patients followed up
      for cervical neoplasia were infected with transcriptionally active HPVs even when
      their Pap smears were negative. In addition, the E6*I/E7 transcript could not be
      detected after surgical treatment in any of the cases that were able to be
      followed up. The E6*I/E7 transcript in the exfoliated cells may prove valuable
      for epidemiological studies of the pathogenesis of HPV infection.

PMID- 7622110
TI  - Development and characterization of an IL-4-secreting human ovarian carcinoma
      cell line.
AB  - Human ovarian carcinoma cell lines were genetically engineered to secrete the
      cytokine interleukin-4 (IL-4) by retroviral-mediated gene transduction. These
      cells were transduced with the LXSN retroviral vector containing the human IL-4
      gene and the neomycin resistance selection marker. Numerous IL-4-secreting clones
      were isolated from different papillary serous carcinoma cell lines, including
      SKOV-3, UCI-101, and UCI-107, and one clone derived from UCI-107 extensively
      characterized. This clone, termed UCI 107E IL-4 GS, was shown to constitutively
      express high levels of IL-4 (i.e., 900 to 1300 pg/ml/10(5) cells/48 hr) for over
      35 passages and 6 months of study. Like the parental cell line (UCI-107), UCI
      107E IL-4 GS cells expressed MHC class I and Her-2/neu surface antigens but did
      not express detectable MHC class II, ICAM 1, CA 125, or IL-4 receptors. No
      increase in expression of surface proteins was noted between parental and UCI
      107E IL-4 GS. The morphology of this clone did not differ from that of the
      parental or LXSN vector control cells; however, parental cells had a faster
      growth rates than transductants. UCI 107E IL-4 GS was sensitive to gamma
      irradiation since as little as 2500 rad killed most of the cells within 10 days
      of irradiation. However, after irradiation, IL-4 secretion continued until about
      Day 8. The potential use of these IL-4-secreting ovarian carcinoma cells as
      vaccines for woman with advanced ovarian cancer will be discussed.

PMID- 7622111
TI  - Phase II trial of methotrexate, vinblastine, doxorubicin, and cisplatin in
      advanced/recurrent endometrial carcinoma.
AB  - A phase II combination chemotherapy protocol combining methotrexate, vinblastine,
      doxorubicin, and cisplatin was designed to evaluate tumor response and survival
      in patients with advanced/recurrent endometrial carcinoma. Thirty patients with
      advanced/recurrent endometrial carcinoma were assigned to chemotherapy treatment
      at 4-week intervals with methotrexate 30 mg/m2 i.v. Days 1, 15, and 22;
      vinblastine 3 mg/m2 i.v. Days 2, 15, and 22; doxorubicin 30 mg/m2 i.v. Day 2; and
      cisplatin 70 mg/m2 i.v. Day 2. After a median of four cycles (maximum number two
      cycles beyond complete regression; minimum six cycles for stable partial
      regression), we observed objective regression in 20 patients (67%) (95% CI, 50,
      84) with complete regression in 8 patients (27%) and partial regression in 12
      patients (40%). Median overall survival was 9.9 months (range, 0.3-34.2), and
      median survival of responders was 11.0 months (range, 2.6-34.2) from initial date
      of response. Toxicity was substantial with two treatment-related deaths and
      consisted predominantly of neutropenia (grade 3 or greater in 93% of the
      patients), alopecia, nausea, emesis, stomatitis, and azotemia. In conclusion,
      MVAC is a highly active outpatient chemotherapy regimen in patients with
      advanced/recurrent endometrial carcinoma, achieving a high complete and partial
      response rate. Toxicity is substantial in this elderly patient population.

PMID- 7622112
TI  - Splenectomy as part of cytoreductive surgery for ovarian carcinoma.
AB  - Splenectomy is sometimes necessary to achieve optimal cytoreduction or manage
      iatrogenic injury in the surgical management of epithelial ovarian cancer (EOC)
      and related conditions. To determine the place of splenectomy in cytoreductive
      surgery a retrospective review was made of patient hospital records. Between
      April 1989 and August 1994, 18 patients were found to have undergone a
      splenectomy as a component of their surgery leading to optimal debulking.
      Morbidity attributable to the splenectomy was minimal, with no significant
      increase in operative time or blood loss. The morbidity attributable to the
      splenectomy was as follows: atelectasis and/or effusion (8), pancreatic tail
      injury (4), thrombocytosis > 10(6)/microliters (3), pancreatic pseudocyst (1),
      partial left adrenalectomy (1), and pulmonary embolism (1). There were no
      instances of overwhelming postsplenectomy infection. Five patients were
      anticipated to require splenectomy and may have benefitted from preoperative
      vaccination against potential pathogens. Three patients were found to have
      splenic parenchymal metastases. Consistent with the international literature,
      these patients had other features consistent with stage IV disease, recurrent
      disease, or poor survival. Consideration should be given to expanding the FIGO
      stage IV classification to include splenic parenchymal disease. Splenectomy is a
      feasible and safe procedure to facilitate optimal tumor debulking; however, the
      potential associated morbidity mitigates against this procedure if significant,
      suboptimal residual disease is left elsewhere.

PMID- 7622113
TI  - Prolonged oral etoposide for refractory advanced uterine leiomyosarcoma.
AB  - The case of a patient with a uterine leiomyosarcoma (LMS) that rapidly recurred
      in the pelvis following primary surgery is reported. The tumor was refractory to
      conventional multiagent chemotherapy that included intravenously administered
      etoposide (VP-16). Etoposide was then administered orally in a prolonged
      schedule; this resulted in a sustained partial response with palliation of
      symptoms. Thus, prolonged oral administration of etoposide may have antitumor
      activity against LMS despite that tumor's resistance to short-term infusion
      schedules of etoposide.

PMID- 7622114
TI  - Systemic lymphadenopathy as the primary symptom of serous surface papillary
      carcinoma of the ovary.
AB  - Serous surface papillary carcinoma (SSPC) is a distinct type of ovarian cancer;
      most of the patients present with extensive intraabdominal disease at the time of
      diagnosis. In a 48-year-old patient with 6-month history of inguinal and then
      scalene lymphadenopathy, although series workup did not disclose any primary
      tumor, an exploratory laparotomy was performed because of the abnormally high
      serum CA-125 level (1024 U/ml) and the pathologic examination of the inguinal
      node suggesting an ovarian origin. At exploration, there was only a discernible
      SSPC lesion on the right ovary; no intraperitoneal spread but extensive lymph
      node metastasis was found. The patient died of disease 30 months after surgery,
      although adjuvant and salvage chemotherapy was given. Ovarian cancer should be
      part of the differential diagnosis in a woman with systemic lymphadenopathy but
      without any evidence of intraabdominal disease.

PMID- 7622115
TI  - Conservative treatment of endometrial cancer permitting subsequent triplet
      pregnancy.
AB  - We report on a 28-year-old woman who received conservative treatment of
      endometrial carcinoma by curettage and progestins. After regression of
      endometrial lesions the patient's infertility was treated by gamete
      intrafallopian transfer (GIFT). Intact triplet pregnancy was diagnosed 3 weeks
      later. The patient was delivered of three infants by caesarean section following
      premature rupture of membranes at 30 weeks of gestation. Subsequent standard
      treatment of endometrial cancer by abdominal hysterectomy and bilateral salpingo
      oophorectomy after 4 weeks revealed no clinical or histological evidence of
      persistent carcinoma. One year after surgery the patient remained without
      evidence of disease. We believe that individualized cancer therapy may be safely
      performed in carefully selected cases.

PMID- 7622116
TI  - Primary fallopian tube adenocarcinoma: clinical complete response after salvage
      treatment with high-dose paclitaxel.
AB  - This Case Report describes a patient with primary fallopian tube cancer who had a
      late recurrence of pelvic disease following adjuvant chemotherapy for early-stage
      disease. Secondary cytoreductive surgery was suboptimal. The bulky residual
      disease was refractory to platinum-based therapy. Extension of the disease to the
      retroperitoneum resulted in obstructed venous return, ureteral obstruction, and
      renal infection. The latter necessitated a third laparotomy and a nephrectomy.
      Upon recovery from surgery and failure of platinum reinduction, the patient was
      treated with high-dose paclitaxel. The large pelvic mass regressed rapidly and
      completely. Current chemotherapy for fallopian tube cancer is briefly reviewed.

PMID- 7622117
TI  - Prolonged stabilization of progressive endometrial stromal sarcoma with prolonged
      oral etoposide therapy.
AB  - We report the case of a patient who has a 23-year history of endometrial stromal
      sarcoma (ESS). She initially underwent tumor-reductive surgery followed by
      adjuvant radiotherapy. The pelvic tumor recurred nearly 8 years later,
      obstructing the ureter and directly invading the bladder. It propagated into the
      vena cava as a thrombus and finally spread into the right heart chambers, leading
      to cardiac failure 13 years after the recurrence. The patient was treated with
      hormonal therapy, multiple resections of the pelvic tumor, chemoembolization, and
      systemic chemotherapy with doxorubicin and cyclophosphamide. She developed
      recurrent intractable symptoms and was started on prolonged oral etoposide
      therapy, which stabilized the size of the pelvic tumor and relieved her symptoms
      for 3 years. Her quality of life has markedly improved without significant
      morbidity. We review the options for treating recurrent ESS and suggest that use
      of prolonged oral etoposide therapy warrants further study in this setting.

PMID- 7622118
TI  - Ovarian strumal carcinoid with markedly high serum levels of tumor markers.
AB  - We report a 54-year-old woman with ovarian strumal carcinoid in association with
      dermoid cyst and mucinous cystadenoma in the same ovary and who had markedly high
      serum levels of CEA (202 ng/ml), CA125 (710 U/ml), and CA19-9 (11,500 U/ml).
      These tumor markers were not found in the thyroid tissue or carcinoid by
      immunohistochemical methods, but their serum levels decreased to below the cutoff
      levels after surgery. In our case, the change of serum levels of these tumor
      markers may be useful for the follow-up after surgery.

PMID- 7622120
TI  - Invasive adenocarcinoma of the cervix following LLETZ (large loop excision of the
      transformation zone) for adenocarcinoma in situ.
AB  - Adenocarcinoma in situ (AIS) of the cervix is a controversial entity which is
      being encountered with increasing frequency. Current critical issues in its
      management are the safety of uterine preservation in younger patients and the use
      of LLETZ conization. A 28-year-old patient was diagnosed with AIS and managed
      with LLETZ. Despite apparently negative margins of resection in the initial
      conizations, the patient was found to have invasive adenocarcinoma 1 year later.
      It is concluded, after review of the pathologic features of AIS, that if
      conservative management of AIS is elected, then standard cold knife conization
      should be performed and not LLETZ. Further study is required to establish the
      overall safety of conservative treatment of cervical AIS, including the use of
      LLETZ.

PMID- 7622119
TI  - Sarcoma botryoides of the cervix treated with limited surgery and chemotherapy to
      preserve fertility.
AB  - Sarcoma botryoides rarely arises in the uterine cervix. It usually presents in
      the adolescent age group and is treated primarily by surgery followed by adjuvant
      chemotherapy. It has been reported in the literature that is possible to limit
      surgery to local excision in stage I cases, when the tumor is confined to the
      cervix. In an attempt to preserve reproductive function in a young female
      patient, we performed cervicectomy alone, followed by adjuvant chemotherapy.
      After 36 months follow-up she remains well, suggesting that limited excision with
      adjuvant chemotherapy may be sufficient for early-stage disease.

PMID- 7622121
TI  - Radiation-induced vesicosacral fistula: treatment with continent urinary
      diversion.
AB  - This is the first Case Report of a vesicosacral fistula related to prior
      radiation therapy. This patient developed recurrent adenosquamous carcinoma of
      the cervix 1 year after radical hysterectomy. She received 5000 cGy to the whole
      pelvis and a 1500-cGy boost to the area of recurrence in the right pelvic
      sidewall. The patient had significant toxicity with recurrent pelvic fistula
      formation ultimately requiring an end sigmoid colostomy. In addition, the patient
      required urethral catheterization due to urinary incontinence secondary to a
      hypertonic bladder. Approximately 14 years after radiation therapy the patient
      developed a vesicosacral fistula. With a nonfunctional bladder, the decision was
      made to proceed with a continent urinary diversion procedure. Despite a prior
      ileocecal resection due to radiation injury, a Miami pouch reservoir was created.
      Postoperatively, the patient remained continent using intermittent
      catheterization of the pouch.

PMID- 7622122
TI  - Prospective multicenter study on CA 125 in postmenopausal pelvic masses.

PMID- 7622123
TI  - [Results of various reconstructive methods after subcutaneous mastectomy and
      objective evaluation of tissue fibrosis with a new measurement procedure].
AB  - Of 35 patients undergoing subcutaneous mastectomy performed within the last 15
      years, 25 were evaluated for follow-up studies. Reconstruction had been achieved
      either using silicone implants or autologous tissue formed from the resulting
      dermal-fat pedicles. The patients were interviewed for subjective results. In
      addition, firmness of the breast according to the classification of Baker was
      investigated. The compressibility of the breast was electronically measured,
      employing a new compression device. In 13 patients, the breast was distorted
      after reconstruction with implants. The deformity did not correlate with
      submuscular or subcutaneous placement of the implants. The aesthetic results
      after dermal-fat pedicle techniques were superior to reconstruction with silicone
      implants. Compressibility to 32% of breast diameter was defined to be a border
      value between a soft and firmer breast, correlating with clinical conditions
      between Baker 2 and Baker 3.

PMID- 7622124
TI  - [Mammography of the reconstructed breast--a comparison of different methods of
      reconstruction].
AB  - The choice of a breast reconstruction technique is considerably influenced by the
      possibility of detecting recurrence. Mammography is the most important diagnostic
      aid in detecting a tumor. We have compared the mammographic evaluation of
      different reconstruction methods. 41 patients were investigated and divided into
      three subgroups: Group I (n = 10): Reconstruction with autologous tissue (TRAM
      flap); group II (n = 22): Reconstruction with silicone gel-filled implants,
      muscle and soft tissue replacement (latissimus flap or submuscular expander
      technique and silicone gel prostheses); group III (n = 9): Reconstruction with
      silicone gel-filled implants. Evaluation was performed employing a scoring
      system. The mammographic appearance of autologous breast reconstructions
      consisting of skin, subcutaneous fat and muscle is comparable to involuted
      breasts. One mammography in this group was of poor, one of acceptable, and eight
      of good quality. Autologous reconstruction is associated with the highest chance
      of recurrence detection. Within group II and III, parts of the reconstructed
      breast are covered by the X-ray absorbing silicone gel prosthesis. In group II,
      seven mammographies were considered poor, 14 acceptable, and one good; in group
      III it was two, four und three respectively. The interpretation depended on the
      implant soft tissue ratio. If thin soft tissue layers cover the prosthesis,
      inspection and palpation become increasingly important, nevertheless it is not
      possible to achieve comparable data as with mammography.

PMID- 7622125
TI  - [A simple classification system for all skin flaps].
AB  - The arterial quality of a skin flap largely depends on the vascular connections
      to the surrounding tissue. We can differentiate three typical vascular structures
      underneath the body's surface: large supporting vessels running parallel to the
      body's surface, transporting vessels (perforators) with a segmental
      vascularization and leading to horizontal (reticular) nets of distribution. These
      structures can be found at the subcutaneous plane, all septofascial planes, and
      the vascular pattern of the muscles. All three structures can provide sufficient
      blood to partially separated and mobilized skin areas (flaps). Each skin flap can
      be classified by the type of enclosed tissue (subcutis, fascia, muscle) and the
      type of blood supply (axial, segmental, reticular). The quality of blood flow
      within a skin flap is not disturbed by separation and mobilization if the
      vascular continuity to the supporting horizontal vessels stays intact. This is
      the case in socalled axial pattern flaps (the supporting vessel is elevated with
      the flap) and in segmental pattern flaps (here continuity stays intact with the
      supporting vessel in deeper layers). In contrast, reticular pattern flaps are
      characterized by a decreased quality of blood flow (sensible to pressure and
      tension) because they lack a direct connection to the supporting vessels. Most
      skin flaps show a complex organization of their vascular structure: they either
      have a parallel support by several structures (improved quality of blood
      circulation) or they contain several structures in sequence within their
      longitudinal axis (decreased quality of blood circulation). This structural
      analysis does not take into account the hemodynamic conditions and their
      influence on the quality of blood circulation which are predisposed by the width
      and the amount of vessels.

PMID- 7622126
TI  - [Traumatic aneurysms of the hand. Description of 5 cases].
AB  - We report about three cases of true aneurysm in the finger artery and one in the
      superficial palmar arch. Three of these developed after blunt trauma. Vascular
      reconstruction was performed either by direct suture or using a venous graft.
      Another case of a false aneurysm after finger replantation is reported.

PMID- 7622127
TI  - [Loss of the replanted thumb by drug-induced ergotism].
AB  - Vasospastic reactions are known to be a complication of thromboembolic
      prophylaxis with Heparin-dihydroergotamine. We describe a rare case after
      successful replantation of an amputated thumb. On the third day after surgery,
      Heparin-dihydroergotamine was administered once. Within three hours, the thumb
      turned pale and cold. At revision, a spasm of the artery proved to be the cause
      of ischemia. Therapeutic efforts were unsuccessful, even intraarterial injection
      of Prostaglandin E1 and the interposition of a vein graft. Amputation became
      necessary. Because of the possible complication with ergotism and the consequence
      of a failed replantation, we suggest not to use Heparin-dihydroergotamine for
      thromboembolic prophylaxis in microsurgery.

PMID- 7622128
TI  - [Contralateral replantation after bilateral traumatic lower leg amputation. Case
      report with 6 year follow-up].
AB  - A 66-year-old patient attempted suicide by jumping in front of a train. The lower
      extremities were amputated at different levels. On the right side, there was a
      complete amputation within the distal third of the lower leg. Proximal to the
      amputation site, there was an extensive soft-tissue and bone defect. On the left
      side, there was a crush injury of the tarsal and mid-tarsal bones. The left lower
      leg showed only few injuries. An ipsilateral (anatomical) replantation was not
      possible. In order to save one lower extremity, we decided to carry out a cross
      over (contralateral) replantation of the right foot to the left lower leg. After
      a follow-up of six years, the patient is able to walk well with her prosthesis on
      the right side and the right foot hooked up to the left lower leg. Functionally,
      this treatment (cross-over replantation-one-side prosthesis of the lower leg) is
      much better than the prosthesis on both extremities, as the result has shown.
      Also from a psychological point of view, it seems to be better for the patient to
      preserve one extremity even with a cross-over replanted foot.

PMID- 7622129
TI  - [Reconstruction of the distal lower extremity defects with distal pedicled
      fasciocutaneous flaps].
AB  - Soft-tissue coverage of defects in the distal lower extremity has its limitations
      because of minimal blood supply to the skin and the thin muscle layer. Split
      thickness skin grafting is impossible in cases of defects of tendons or bones.
      Local flaps are applicable only for smaller defects. With the cross-leg flaps, it
      is necessary to immobilize the patient for a long time. Special microsurgical
      technique and knowledge are needed for the free flaps. Fasciocutaneous flaps of
      the lower extremity after Donski and Fodgestam are simpler and safer than the
      other methods. From 1987 to 1992, this method was successfully used on 15
      patients in the Department of Plastic Surgery of Sisli Etfal Hospital in
      Istanbul. In the two-thirds of those patients, accidents were the cause of the
      defects. The advantages of this methods are: simpler technique, larger flap
      surface, earlier mobilisation of patients, better adaptation of the flap to its
      neighbourhood regarding colour and thickness.

PMID- 7622130
TI  - [Free tissue transplantation for correction of calf asymmetry. A case report].
AB  - A case of aesthetic calf augmentation by a microsurgical free deepithelialized
      VRAM-flap is reported. As a result of poliomyelitis infection in childhood and
      atrophy of the m. gastrocnemius medialis sinister, the contour of the left calf
      was deformed. The reconstruction by autologous material was performed by use of
      the free VRAM-flap. The indications, advantages, and disadvantages of this method
      compared to calf augmentation by silicon prostheses are discussed.

PMID- 7622131
TI  - [Transitory lesion of the radial nerve after fall onto the outstretched arm].
AB  - A patient presented with a bony avulsion of the radial collateral ligament of the
      elbow combined with a partial lesion of the radial nerve after a fall onto the
      outstretched arm. Probably the nerve was compressed at its penetration through
      the lateral intermuscular septum by a sudden contraction of the triceps tendon.
      Conservative treatment led to complete recovery.

PMID- 7622132
TI  - [Wartenberg syndrome, caused by a split tendon of the brachioradialis muscle. A
      report of a rare anatomic variation].
AB  - We report a case of radial sensory nerve entrapment caused by a variation of the
      brachioradialis tendon. The nerve passed through the split tendon and gliding was
      hindered at this level. After resection of the supernumerary dorsal part of the
      tendon, relief of pain could be achieved in the 40-year-old patient.

PMID- 7622133
TI  - [Costs and long-term results of plastic surgery treatment of decubitus ulcers in
      paraplegic patients].
AB  - Costs and long-term results of plastic surgical procedures were evaluated in 17
      paraplegics with a mean age of 39 years and Campbell-Grade 5 pressure sores.
      Seven sacral, nine ischial and one trochanteric ulcers were treated by
      myocutaneous or fasciocutaneous flaps. The mean hospitalization period was 82
      days: up to 44 days in the plastic surgical department, 29 days in referring
      hospitals. During the follow-up period, averaging 18 (6 to 33) months, four
      patients suffered recurrences, all of them ischial sores. Evaluated regarding
      occupational resumption or duration of wheelchair mobility, eleven patients
      achieved full and two patients partial rehabilitation. The success rate justifies
      the operative procedures. Cost reduction by shortened hospitalization could be
      achieved through earlier transfer of patients to specialized units since
      preoperative preparation requires rarely more than one week and surgical relief
      can usually be achieved within a confined period of time. Orthopaedic deformities
      contributed to the majority of sores and to all recurrences.

PMID- 7622134
TI  - Insular claustrum of the dog--a morphometric investigation of cellular structure.
AB  - Investigation of the dog's insular claustrum was performed using morphometric
      methods. The brains of 14 dogs (7-14 year-old) were studied. The size, shape and
      density of neurons are different in various parts of the insular claustrum. The
      posterior part, related to the visual system, is heterogenous and possesses
      medium-sized and small densely packed neurons, the average cross-sectional area
      of cell body being 175.8 +/- 45.5 micron2. The similar average cross-sectional
      area of cell body (174.1 +/- 55.3 micron2) was found in the central part of the
      insular claustrum. However, neuronal architecture is here less heterogenous and
      neurons are less densely arranged. The anterior part, connected mainly with the
      frontal and motor cortex, is more homogenous and contains loosely arranged
      neurons of a rather large size (average size--198.7 +/- 53.46 micron2).

PMID- 7622135
TI  - Morphometric parameters of some hypothalamic nuclei: age-related changes.
AB  - The morphometric analysis of some hypothalamic nuclei was performed on 20 brains
      of subjects of both sexes aged from 29 to 79 years. They were divided into two
      groups: below and above the age of 60. Supraoptic (SON), lateral tuberal (LTN)
      and lateral mammillary (LMN) nuclei were investigated. In the group of aged
      subjects a decrease in cross-section area of neuron nuclei was observed in all
      investigated structures, expressed most in the LTN. A considerable increase in
      the neuron density with age was found in the LTN. The size of neuron cell bodies
      and the number of neurons did not change significantly with age in any of the
      investigated nuclei.

PMID- 7622136
TI  - The spinal accessory nerve in human embryos at 6th week (stages 16 and 17).
AB  - Investigations were made on serial sections of human embryos at developmental
      stages 16 and 17 (37-41 days). The spinal nucleus of the accessory nerve presents
      well delimited cellular group in the dorsplateral part of the ventral horn of the
      spinal cord. The migration zone is still present. In embryos of stage 16 the
      spinal accessory nerve joints the fibers originating from the nucleus ambiguous.
      This takes place at the level of the inferior ganglion of the vagus nerve. In
      stage 17 the secondary rami of the accessory nerve develop. This is correlated
      with the differentiation of the sternocleidomastoid and trapezius muscles.

PMID- 7622137
TI  - Vascularization of the brain in guinea pig. I. Gross anatomy of the arteries and
      veins.
AB  - The brain of the guinea pig is supplied by branches of the vertebral, basilar,
      and internal carotid arteries. There is no anterior communicating artery. The
      main blood supply to the brain is through the vertebral-basilar system.

PMID- 7622138
TI  - Ultrastructure of the secondary yolk sac in pig's embryo.
AB  - During the investigated period of development the pig embryo secondary yolk sac
      consists of two parallel epithelia (endodermal and mesodermal) separated by a
      layer of vascularized mesenchyme. Endoderm cells and blood vessels undergo
      morphological changes connected with the embryo age. The development of the blood
      vessels is at the vasculogenesis stage. Blood stem cells, erythroblasts,
      megakaryocytes and platelets were observed in the lumen of vessels. A comparison
      our results with the development of the pig embryo liver shows that the
      transferring the haemopoetic function from the yolk sac to the liver begins on
      about 27 dpc. Until 51 day of embryo development the yolk sac does not show any
      signs of involution. Possibly yolk sac supports the liver in its haemopoetic
      function until the time when that organ becomes a fully efficient haemopoetic
      organ.

PMID- 7622139
TI  - Ganglia of the cervical part of the sympathetic trunk in the white rat. Sources
      of blood supply and angioarchitectonics.
AB  - Each ganglion of the cervical part of the sympathetic trunk in white rat is
      supplied by several arteries of diameter of 15--30 micrometers. The arteries
      arise from three sources: 1) large vessels adjacent to the ganglia, 2) vascular
      net of connective and muscular tissues surrounding the ganglion, 3) vessels of
      nerves and interganglionic rami. The vascular network of the cervical sympathetic
      ganglia was connected with the vascular plexus of the vagus nerve and cervical as
      well as brachial plexuses.

PMID- 7622140
TI  - The atrioventricular and ventriculoatrial branches of the human coronary arteries
      in relation to the type of arterial vascularization.
AB  - Studies were performed on 130 hearts removed from cadavers of adults of both
      sexes. The atrioventricular (A-V) and ventriculoatrial (V-A) branches are vessels
      which supply both the atrial and ventricular walls through the recurrent rami. A
      V and A-V branches often form the superficial and deep networks in relation to
      the right coronary artery and cirumflex branch of the left coronary artery. The
      described vessels were observed in 7,5% of cases in the right type, in 53,4% of
      cases in the symmetrical type of arterial vascularization, and in 23% of
      instances in the left type of arterial supply.

PMID- 7622141
TI  - Variability of the renal lymph nodes in Wistar rats.
AB  - Studies were carried out on 190 adult Wistar rats. The size and number of both
      left and right renal lymph nodes were studied. Observations were made under
      stereomicroscope. The analysis of renal lymph node variability was based on lymph
      nodal physiological compartments hypothesis. It was found that in the Wistar rats
      the variability of the renal lymph nodes is related to sex and the side of the
      body. In majority of rats, both males and females, the left renal lymph nodes
      were single and less variable than the right ones.

PMID- 7622142
TI  - IL6 and IL6 receptor expression in Burkitt's lymphoma and lymphoblastoid cell
      lines: promotion of IL6 receptor expression by EBV.
AB  - We have analysed a panel of different Burkitt's lymphoma (BL) and lymphoblastoid
      cell lines (LCLs) for the expression of IL6 and IL6 receptor (IL6R). Epstein-Barr
      Virus (EBV) positive or negative BL cell lines and the corresponding
      lymphoblastoid cell lines (LCL), derived from EBV immortalized mononuclear cells
      of the BL patients, were tested for the expression of IL6 mRNA and protein by
      Northern blot experiments and ELISA, and for the expression of the IL6R mRNA and
      protein by Northern blot Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR)
      and flow cytometry. Our results demonstrate that six out of 19 Burkitt's lymphoma
      cell lines produced IL6 constitutively. All three cell lines infected with the
      EBV substrain B95-8 (B95-8 convertants) produced IL6, in contrast to the original
      EBV negative lines and to the cell lines infected with the EBV substrain P3HR1
      (P3HR1 convertants). The produced IL6 was biologically active as shown by
      proliferation of the IL6 dependent cell line TEPC 1033 C2. The two BL cell lines
      with the highest level of IL6 production (190 pg/ml and 550 pg/ml) expressed in
      addition IL6R molecules on the cell surface. Monoclonal antibodies directed
      against IL6 did not inhibit the growth of these two BL cell lines, thus excluding
      autocrine stimulation in these lines. IL6R expression could be further
      demonstrated in all LCLs analysed, in five out of seven EBV positive BLs and two
      out of three B95-8 convertants, but only in one out of the six EBV negative BL
      cell lines. Our results suggest that EBV in immortalized B cells and in Burkitt's
      lymphoma cells can promote IL6 receptor expression.

PMID- 7622143
TI  - Diagnosis of avascular necrosis of the femoral head in patients treated for
      lymphoma.
AB  - Avascular necrosis of bone (AVNB) is a well-known but rare complication of
      chemotherapy for lymphoma with a reported incidence ranging from 1 to 10 per
      cent. Early diagnosis is essential for optimal therapeutic management. Using MRI,
      the most sensitive means of detecting the earlier stages of AVNB, 100 patients
      treated with standard chemotherapy for lymphoma were assessed. Fifteen were found
      to have changes of AVNB, 10 with early changes but five with advanced segmental
      collapse of the femoral head. None with AVNB had more than the standard course of
      corticosteroids. Almost a quarter of the study group complained of joint pain
      during and/or after their treatment, a third of whom were found to have AVNB; a
      strong indicator to screen all those with pain. However, 40 per cent of those
      with AVNB were asymptomatic. The clinical significance of the 'silent hip' is yet
      to be elucidated.

PMID- 7622144
TI  - Prognostic factors in myelodysplastic syndromes: analysis of five scoring
      systems.
AB  - PURPOSE: To evaluate the prognostic significance of five scoring systems applied
      with predictive trends to myelodysplastic syndromes (MDS). PATIENTS AND METHODS:
      This study was comprised of 226 patients with MDS diagnosed in accordance with
      the FAB criteria and followed up in our department between January 1975 and April
      1992. The following MDS subtypes were found: refractory anaemia (RA), 59 cases;
      refractory sideroblastic anaemia (RSA), 49 cases; refractory anaemia with excess
      of blasts (RAEB), 56 cases; RAEB in transformation (RAEB-T) 48 cases; and chronic
      myelomonocytic leukemia (CMML), 14 cases. The following scoring systems were
      applied: Mufti's 1985, Varela's 1985, Sanz's 1989, Rubio's 1991 and Aul's 1992.
      The statistical analysis was performed according to Kaplan-Meier actuarial
      systems and the log-rank test of survival. RESULTS: (1) Three groups (A, B and C)
      can be defined by Mufti's system, with median survival of 54.0, 16.0 and 8.5
      months, respectively. The majority of cases (138) were included in group B. Group
      A did not reach 25 per cent of actuarial survival probability, whereas groups B
      and C did at 31.1 and 12.2 months, respectively. With regard to the morphologic
      subtypes, RA and RSA were included in groups A and B, and RAEB, RAEB-T and CMML
      pertained mostly to group C. Sixty-six cases (33.6 per cent) developed into acute
      leukemia (AL) corresponding to those last groups. (2) The three groups defined by
      Varela's system (0-1, 2-5 and 6 or more) had median survival of 91.8, 24 and 13
      months, respectively. As in the former system, group 0-1 did not reach 25 per
      cent actuarial probability, this appearing at 60 and 20 months, respectively, in
      groups 2-5 and > 6. The distribution of the cytological varieties, RA and RSA
      among the groups is heterogenous although they were more common within the cases
      included in groups 0-1. All cases developing AL were included in the groups 2-5
      and > 6. (3) The three groups of the system proposed by Sanz (0-1, 2-3 and 4-5)
      had median survival of, 55.3, 15 and 12.6 months respectively. As in the
      preceding cases, group 0-1 did not reach the 25 per cent actuarial probability,
      while this figure appeared at 28.2 months for group 2-3 and at 19.3 months for
      group 4-5. RA and RSA varieties were included chiefly in group 0-1, while RAEB
      and RAEB-T appear mostly in groups 2-3 and 4-5. The distribution of the cases and
      the evolution of AL was heterogeneous according to this system, although they
      predominate in groups 2-3 and 4-5. (4) Using the Aul's system, three groups A, B
      and C were defined. The median survival time was 14 months for group C and 24
      months for group B. For group A, the median survival was not reached. RA and RSA
      were exclusive for group A, while RAEB and RAEB-T varieties were outstanding in
      group C. Regarding the evolution to leukemia the differences observed had no
      statistical relevance. (5) Three prognostic groups were defined by Rubio's system
      (namely 0-2.5, 3-5.5, > or = 6) with median survival of 53.3, 16.8 and 10.5
      months, respectively. A striking difference was seen when studying the cumulated
      survival observed, in each of the three percentages considered, between the
      groups. The different cytological varieties were reasonably distributed with
      higher incidence of RA and RSA in group I and RAEB, RAEB-T and CMML in group III.
      This system offers statistical significance when comparing RA with RSA, RAEB with
      RAEB-T and, obviously RA+RSA with RAEB+RAEB-T+CMML. The evolution into AL also
      showed statistical significance with respect to the three groups.

PMID- 7622146
TI  - Current awareness in hematological oncology.

PMID- 7622145
TI  - Prognostic factors for primary gastrointestinal lymphoma.
AB  - The gastrointestinal tract is a common primary extranodal site for non-Hodgkin's
      lymphoma. There is however no uniform consensus on its pathological
      classification, clinical staging system and management. This paper reports the
      experience in the management of 425 Chinese patients with primary
      gastrointestinal lymphoma in Hong Kong from January 1975 to June 1993. There were
      230 (54 per cent) males and 195 (46 per cent) females. Their median age was 53
      years. The primary sites were: the esophagus in three (1 per cent), stomach in
      238 (56 per cent), small intestine in 131 (31 per cent) and large intestine in 53
      (12 per cent). According to the Working Formulation, there were 20 (4.7 per cent)
      small lymphocytic, 10 (2.4 per cent) follicular small cleaved cell, 15 (3.5 per
      cent) follicular mixed, five (1.2 per cent) follicular large cell, 40 (9.4 per
      cent) diffuse small cleaved cell, 50 (12 per cent) diffuse mixed, 181 (43 per
      cent) diffuse large cell, 30 (7.1 per cent) immunoblastic, five (1.2 per cent)
      lymphoblastic, 10 (2.4 per cent) diffuse small non-cleaved cell and 50 (14 per
      cent) unclassifiable lymphoma. Immunophenotyping was performed in 199 (47 per
      cent) patients: 90 per cent B-cell, 7 per cent T-cell and 3 per cent uncertain.
      According to a Manchester system, 81 (19 per cent) patients had stage I disease,
      44 (10 per cent) stage II, 85 (20 per cent) stage III and 215 (51 per cent) stage
      IV. B symptoms were present in 275 (65 per cent) patients and bulky disease in
      104 (25 per cent). Surgery followed by chemotherapy was the mainstay of
      treatment. Of the 408 patients treated, 63 per cent had a complete remission with
      relapse rate of 42 per cent. For those with complete remission, 47 per cent were
      free from disease at 5 years. The overall median survival of all patients was 45
      per cent at 5 years. Multivariate analysis revealed that significant independent
      prognostic factors predicting better survival were young age of < 60 years, low
      grade histology, stage I and II disease and absence of bulky tumour. For gastric
      lymphoma, aggressive surgery did not significantly improve their outcome.
      Chemotherapy appears to play an important role in the management of
      gastrointestinal lymphoma. Better classification of the primary gastrointestinal
      lymphoma and more refined stratification of the patients according to the
      prognostic variables may allow individualization of treatment. Prospective
      randomized studies are essential to define the relative roles of surgery,
      chemotherapy and radiotherapy.

PMID- 7622147
TI  - An equivalent body surface charge model representing three-dimensional
      bioelectrical activity.
AB  - A new surface-source model has been developed to account for the bioelectrical
      potential on the body surface. A single-layer surface-charge model on the body
      surface has been developed to equivalently represent bioelectrical sources inside
      the body. The boundary conditions on the body surface are discussed in relation
      to the surface-charge in a half-space conductive medium. The equivalent body
      surface-charge is shown to be proportional to the normal component of the
      electric field on the body surface just outside the body. The spatial resolution
      of the equivalent surface-charge distribution appears intermediate between those
      of the body surface potential distribution and the body surface Laplacian
      distribution. An analytic relationship between the equivalent surface-charge and
      the surface Laplacian of the potential was found for a half-space conductive
      medium. The effects of finite spatial sampling and noise on the reconstruction of
      the equivalent surface-charge were evaluated by computer simulations. It was
      found through computer simulations that the reconstruction of the equivalent body
      surface-charge from the body surface Laplacian distribution is very stable
      against noise and finite spatial sampling. The present results suggest that the
      equivalent body surface-charge model may provide an additional insight to our
      understanding of bioelectric phenomena.

PMID- 7622148
TI  - A model of gastric electrical activity in health and disease.
AB  - The idea of diagnosing gastric dysfunction from noninvasive measurements of
      gastric electrical activity (GEA) is intuitively appealing, but the predictive
      accuracy of the cutaneous signal, especially that of its amplitude, is still in
      question. Mathematical modeling provides a means of investigating, analyzing, and
      predicting GEA measured percutaneously. In this study, a model of GEA applicable
      both in health and disease was developed and simulated for a cylindrical body
      surface. Body-surface maps of the simulated electrogastrogram (EGG) were
      generated at a 20 by 20 array of sites on the model's surface, and the accuracy
      of the percutaneous method in detecting simulated gastric electrical
      abnormalities was determined. The relationship between the amplitude of the
      simulated surface EGG and the velocity of propagation of the myogenic activity
      was also investigated. This was compared to a similar investigation of the
      fluctuations in the amplitude of the surface EGG with the velocity of propagation
      of the serosal activity measured in humans. The diagnostic accuracy of the
      measured cutaneous EGG in humans was also determined. The results obtained from
      the mathematical model show that the amplitude of the electrogastrogram increases
      with the propagation velocity of GEA. Similar results were obtained from the
      experimental measurements. The amplitude of the simulated and measured cutaneous
      signal correlated well (p < 0.05) with the phase shift of the simulated and
      measured activities, (-0.85, -0.54), respectively. Serosal normal activity,
      tachygastria, and uncoupling were detected 67%, 90%, and 0% of the time,
      respectively, at the cutaneous electrode in humans. In simulations, normal
      activity and tachygastria were accurately detected at all 400 sites on the
      surface. Uncoupling simulated with 50% of the myogenic sources "diseased" was
      detected at only 20 of the 400 sites. The results confirm that the amplitude of
      the cutaneous signal is a function of the velocity of propagation of the myogenic
      signal. It also confirms that while GEA in health may be accurately predicted
      from percutaneous recordings, frequency and phase/coupling abnormalities are
      poorly detected from single-channel electrogastrograms. This suggests the use of
      multiple-channel surface recordings in clinical electrogastrography.

PMID- 7622149
TI  - Segmentation of brain electrical activity into microstates: model estimation and
      validation.
AB  - A brain microstate is defined as a functional/physiological state of the brain
      during which specific neural computations are performed. It is characterized
      uniquely by a fixed spatial distribution of active neuronal generators with time
      varying intensity. Brain electrical activity is modeled as being composed of a
      time sequence of nonoverlapping microstates with variable duration. A precise
      mathematical formulation of the model for evoked potential recordings is
      presented, where the microstates are represented as normalized vectors
      constituted by scalp electric potentials due to the underlying generators. An
      algorithm is developed for estimating the microstates, based on a modified
      version of the classical k-means clustering method, in which cluster orientations
      are estimated. Consequently, each instantaneous multichannel evoked potential
      measurement is classified as belonging to some microstate, thus producing a
      natural segmentation of brain activity. Use is made of statistical image
      segmentation techniques for obtaining smooth continuous segments. Time varying
      intensities are estimated by projecting the measurements onto their corresponding
      microstates. A goodness of fit statistic for the model is presented. Finally, a
      method is introduced for estimating the number of microstates, based on
      nonparametric data-driven statistical resampling techniques.

PMID- 7622150
TI  - Open loop control of multiple drug effects in anesthesia.
AB  - Current open-loop computer-controlled infusion pumps do not explicitly control
      the transient adverse side effects of intravenous drugs during anesthesia. We
      used optimal control principles to synthesize a single-input multiple-output
      controller that regulates concentrations at the site of desirable drug effect
      while penalizing excessive side-effect drug concentrations. The cost function
      incorporates model-based predictions of future effect-site concentrations, and
      the capability of the anesthesiologist to anticipate upcoming surgical events.
      The controller was evaluated and then compared with alternative control
      strategies through computer simulation of a physiologically based pharmacokinetic
      model for the intravenous drug alfentanil. Multiple-effect control offers an
      analytic approach to limit the overshoot in adverse side-effect concentrations at
      the consequence of increasing the time to achieve the desired drug effect.

PMID- 7622151
TI  - Simulator for laser photocoagulation in ophthalmology.
AB  - The practice of laser photocoagulation plays a major role in the ocular therapy,
      but the persistence of many postoperative complications denotes genuine
      difficulty in mastering the technique. The authors present a device which, thanks
      to the use of simulation, enables actual practice to be dissociated from
      apprenticeship. While complying with the constraints of realism with regard to
      habitual conditions of laser use, the device offers access to a wide variety of
      clinical situations. The apparatus is built around the traditional instrument. A
      virtual image of the fundus is produced in real time from the sensors which
      detect the actual gestures used. The calculations make use of textured
      geometrical models. Digitized color photographs are organized to form a database
      which reflects the diversity of pigmentations and pathologies. A software
      interface has been developed to facilitate the use of the device. The prototype
      is operated using a PC-compatible computer; it displays the images at the rate of
      at least seven per second on a miniature CGA screen incorporated in the slit
      lamp. It is currently being validated for clinical applications. Above and beyond
      apprenticeship in laser photocoagulation, its potential applications extend to
      the entire field of ophthalmogical symptomatology and, more broadly, to the
      simulation of any examination conducted with the help of binocular or endoscopic
      optics.

PMID- 7622152
TI  - The use of a current sheet applicator array for superficial hyperthermia:
      incoherent versus coherent operation.
AB  - There are a number of potential advantages to be gained by using an array of
      applicators in hyperthermia treatments compared with single applicator systems.
      These advantages include the possibility of greater spatial control of power
      deposition and conformability to nonplanar sites. Arrays of applicators can be
      driven either coherently or incoherently. In the case of coherent operation, an
      added advantage is the ability to steer power deposition by varying the phases of
      the antennas. In this study, we investigated the relative merits of the two modes
      of operation when a 2 x 2 planar array of current sheet applicators is used. The
      effective field size (EFS) of the array was calculated using a Gaussian beam
      representation of the applicators on a layered model in which the fat layer had
      its thickness varied. Good agreement was obtained between the square of the
      electric field distribution (E2) and quantitative experimental results. It is
      shown that when the planar array is used with a fat layer greater than about 2 mm
      present, it should be driven incoherently as this results in a significantly
      larger EFS than that obtained when the array is driven coherently.

PMID- 7622153
TI  - Artificial neural network control of FES in paraplegics for patient responsive
      ambulation.
AB  - This paper describes an ART-1-based artificial neural network (ANN) adapted for
      controlling functional electrical stimulation (FES) to facilitate patient
      responsive ambulation by paralyzed patients with spinal cord injuries. This
      network is to serve as a controller in an FES system developed by the first
      author which is presently in use by 300 patients worldwide (still without ANN
      control) and which was the first and the only FES system approved by the FDA. The
      proposed neural network discriminates above-lesion upper-trunk electromyographic
      (EMG) time series to activate standing and walking functions under FES and
      controls FES stimuli levels using response-EMG signals. For this particular
      application, we introduce several modifications of the binary adaptive resonance
      theory (ART-1) for pattern recognition and classification. First, a modified on
      line learning rule is proposed. The new rule assures bidirectional modification
      of the stored patterns and prevents noise interference. Second, a new reset rule
      is proposed which prevents "exact matching" when the input is a subset of the
      chosen pattern. We show the applicability of a single ART-1-based structure to
      solving two problems, namely, 1) signal pattern recognition and classification,
      and 2) control. This also facilitates ambulation of paraplegics under FES, with
      adequate patient interaction in initial system training, retraining the network
      when needed, and in allowing patient's manual override in the case of error,
      where any manual override serves as a retraining input to the neural network.
      Thus, the practical control problems (arising in actual independent patient
      ambulation via FES) were all satisfied by a relatively simple ANN design.

PMID- 7622154
TI  - Spectral patterns and frequency response characteristics of arterial pressure in
      heart paced dogs.
AB  - The role of heart rate in buffering and/or generating aortic pressure (AP)
      oscillations that occur at rest and in response to oscillatory blood volume
      shifts was studied. Six supine dogs with chronic AV blockade were used to
      examine: 1) resting HR and AP spectra when the ventricular rate was controlled by
      atrial depolarization (natural sinus rhythm); 2) resting AP and stroke volume
      (SV) spectra when the heart was AV sequentially paced at 60, 120, and 180 bpm
      before and after ganglionic blockade; and 3) the frequency response
      characteristics of AP and SV to whole-body sinusoidal acceleration (+/- 2gz,
      0.008-0.23 Hz) at each heart rate before and after ganglionic blockade. During
      atrial regulation of HR, the spectra of both AP and HR had dominant peaks located
      at the breathing frequency (0.2-0.4 Hz) and relatively smaller peaks centered at
      approximately 0.05 Hz. During constant heart rate pacing, the spectra of AP had a
      dominant component at approximately 0.05 Hz. The power of this component was: 1)
      larger than during atrial regulation, 2) increased with increasing pacing rate,
      and 3) abolished by ganglionic blockade. There was no effect of pacing rate or
      ganglionic blockade on SV spectra. During oscillatory acceleration, AP regulation
      in the heart paced dogs was frequency dependent. Regions of good regulation
      occurred below 0.016 Hz and above 0.1 Hz, and poor regulation between 0.035 and
      0.075 Hz centered at approximately 0.05 Hz. The oscillations in the poor
      regulation region were enhanced by increased pacing rate. After ganglionic
      blockade, the frequency response of AP was primarily hydraulic (low-pass). The
      frequency response of SV had a neural component. We conclude that: 1) resting AP
      fluctuations at respiratory frequencies resulted from respiration-linked HR
      variation; 2) the 0.05-Hz fluctuations in AP during rest and the poor regulation
      of AP at 0.05 Hz during acceleration resulted from a peripheral vascular response
      that lagged disturbances by approximately 10 s; 3) HR regulation was important in
      minimizing AP variation in the 0.05-Hz region both at rest and during oscillatory
      acceleration; and 4) inotropic control of SV was an important component of AP
      regulation during low-frequency acceleration.

PMID- 7622155
TI  - A frequency domain analysis of spatial organization of epicardial maps.
AB  - Mapping of organized rhythms like sinus rhythm uses activation times from
      individual electrograms, and often assumes that the map for a single activation
      is similar to maps for subsequent activations. However, during fibrillation,
      activation times and electrograms are not easy to define, and maps change from
      activation to activation. Volume and complexity of data make analysis of more
      than a few seconds of fibrillation difficult. Magnitude Squared Coherence (MSC),
      a frequency domain measure of the phase consistency between two signals, can be
      used to help interpret longer data segments without defining activation times or
      electrograms. Sinus rhythm, flutter, and fibrillation in humans and swine were
      mapped with an array of unipolar electrodes (2.5 mm apart) at 240 sites on the
      atrial or ventricular epicardium. Four-second data segments were analyzed. One
      site near the center of the array was chosen ad hoc as a reference. MSC maps were
      made by measuring mean MSC from 0-50 Hz between every point in the array relative
      to the reference. Isocoherence contours were drawn. The effects of bias in the
      coherence estimate due to misalignment were investigated. Average MSC versus
      distance from the reference was measured for all rhythms. Results indicate that
      in a 4-s segment of fibrillation, there can exist some phase consistency between
      one site and the reference and little or none between a second site and the
      reference even when both sites are equidistant from the reference. In
      fibrillation, isocoherence contours are elongated and irregularly shaped,
      reflecting long-term, but nonuniform, spatial organization. That is, activation
      during fibrillation cannot be considered as random over a 4-s interval. Bias in
      the coherence estimate due to misalignment is significant for sinus rhythm and
      flutter, but can be corrected by manual realignment. Average MSC drops with
      distance for all rhythms, being most pronounced for fibrillation, MSC maps may
      provide insights into long-term spatial organization of rhythms that would
      otherwise be cumbersome and difficult to interpret with standard time domain
      analysis.

PMID- 7622156
TI  - Application of a multivariate technique to Raman spectra for quantification of
      body chemicals.
AB  - Raman spectroscopy is a highly specific technique for the identification of
      molecules by way of the associated characteristic spectra. The aim of this
      feasibility study is to assess the combination of the multivariate calibration
      technique of Partial Least-Squares with Raman spectroscopy for the estimation of
      glucose, lactic acid, and urea concentrations in the presence of each other in a
      water substrate. The instrument is a CCD-based Raman spectrometer utilizing the
      514.5 nm argon laser line. The estimates for the analyte concentrations yielded a
      standard deviation of concentration residuals of 20.71 mg/dL for glucose, 12.92
      mg/dL for lactic acid, and 19.07 mg/dL for urea.

PMID- 7622157
TI  - Removal of power line interference in signal-averaged electrocardiography
      systems.
AB  - A method for line interference reduction to be used in signal-averaged
      electrocardiography (SAECG) systems is proposed and its performance is analyzed.
      This new method is an adaptation of a previously reported technique for removal
      of line interference from conventional electrocardiograms. It involves the
      recording of a line reference signal simultaneous with the lead signals, so that
      a shifted and scaled version of it can be used to subtract line interference from
      the leads. It is shown that this line interference subtraction method can reduce
      line interference effectively and without introducing any additional noise into
      the ECG signal. It is also shown that Late Potential diagnostic decisions are not
      altered when this filter is applied. It is recommended that this technique be
      used in SAECG when line interference is unavoidable.

PMID- 7622158
TI  - On the detection of QRS variations in the ECG.
AB  - Detection of subtle beat-to-beat variations in the morphology of the ECG is
      complicated by the effects of alignment errors and respiration. A method of
      directly estimating the alignment error (trigger jitter) from an ECG is derived
      by relating the variance to the squared slope of the averaged QRS complex.
      Results based on recordings obtained from 12 normal subjects and alignment
      performed by the cross-correlation method showed that the alignment errors were
      dependent upon the choice of the alignment channel, with the best distribution of
      the errors occurring when alignment was based on the vector magnitude of the
      three orthogonal leads. The estimated average alignment errors ranged from 0.33
      0.42 ms, which were near the optimal value of 0.29 ms based on the sampling rate
      of 1000 samples/s. It was shown that the effects of respiration could be reduced
      by normalizing the amplitude of the QRS complexes. It was also estimated that a
      significant proportion of the variation (0.54-0.67) in the normalized ECG's could
      be attributed to alignment errors and noise.

PMID- 7622159
TI  - Gortner's contribution to nursing knowledge development.
AB  - The building of nursing science is the core of knowledge development in nursing.
      Throughout the years, Gortner has shared her thoughts about science, nursing
      science, and ways to develop the scientific base of nursing. This paper is a
      synthesis of Gortner's views on science, nursing science, and nursing science
      building. It is based on her publications and emphasizes her contributions.

PMID- 7622160
TI  - A Heideggerian hermeneutical analysis of older women's stories of being strong.
AB  - As people in our society live longer, affirming the quality of their lived
      experience becomes more important. The purpose of this study was to ascertain and
      analyze the meanings of "being strong" as revealed from within the stories of
      older women. A Heideggerian hermeneutical approach, from a critical feminist
      perspective, was the methodology used. The sample consisted of 12 women, 7 White
      and 5 Black, over the age of 65. A team of researchers analyzed the transcripts.
      Findings consisted of three constitutive patterns: "Surviving," "Finding
      Strength," and "Gathering the Memories ... Seeing the Patterns."

PMID- 7622161
TI  - A conceptual model for community interagency collaboration.
AB  - Although interagency community collaboration has been suggested to increase
      programming and decrease costs, theoretical understanding for this in nursing is
      limited. A conceptual framework for community interagency collaboration is
      described that depicts collaboration as a function of environmental conditions,
      organizational situations, and task characteristics. Transactional patterns
      including intensity, formalization, interrelational patterns, and structured
      relationships are discussed as are outcomes pertaining to organizations,
      interorganizational relations, clients, and communities.

PMID- 7622162
TI  - Beyond dichotomies in the nursing of persons and families.
AB  - The dichotomy of individual and family nursing has served the discipline well.
      However, the time has come for a reconciliation of these perspectives and the
      redefinition of nursing as inclusive of both individuals and families. A
      conceptual framework that draws distinctions among four different nursing focuses
      of persons and families is described.

PMID- 7622163
TI  - Transcending alcoholic denial.
AB  - Denial is a characteristic of alcoholism and other drug addictions that must be
      appreciated in order to understand the recovery process. The purpose of this
      field study was to describe the internal processes that alcoholics experience as
      they transcend denial. Grounded theory methods guided data collection and
      analysis. The author observed and interviewed 42 patients in an inpatient
      alcoholism treatment facility, then followed 30 participants over a 3-year
      period. Using the constant comparison method of data analysis, a basic social
      process theory of transcending alcoholic denial emerged. The theory has five
      progressive stages: reacting to the critical event; role disaffiliation;
      ambiguous anticipation; peer affiliation; and acceptance. The theory also
      elucidates consequences of unresolved stages.

PMID- 7622164
TI  - King's framework and theory in Japan, Sweden, and the United States.
AB  - In this article, we present our work in extending and testing Imogene King's
      conceptual framework and theory in Japan, Sweden, and the United States.
      Comparing and contrasting cultural relevance, methodology, and issues of validity
      provide examples of international scholarship and knowledge development that
      result from networking and collaboration.

PMID- 7622165
TI  - Becoming gold-plated: Chinese nurses studying abroad.
AB  - The purpose of this interpretive study is to describe the experience of Chinese
      nurses studying abroad. Twenty-three nurses living in Taiwan, who had studied in
      the United States for university degrees, were interviewed in 1990. A central
      process was "Becoming gold-plated." The first major theme was "Enormous pressure
      and sacrifice," with the subthemes of "Self-doubt," "Language difficulties,"
      "Isolation and loneliness," and "Separation and guilt." The second major theme
      was "Transformed self," with subthemes of "High aspiration" and "New perspective
      on life." In spite of the hardships of study abroad, Chinese nurses felt pride in
      their accomplishment and self-respect for the knowledge and sophistication they
      gained.

PMID- 7622166
TI  - Congruence of decisions between patients and their potential surrogates about
      life-sustaining therapies.
AB  - Decisions concerning life-sustaining treatments and the congruence in decision
      making between patients and potential surrogates were examined. The ability of a
      patient-chosen surrogate to make decisions reflecting the wishes of that patient
      was estimated. Thirty patient-surrogate pairs independently responded to
      vignettes of five treatments. Patients and surrogates made similar decisions on
      all treatments except cancer chemotherapy, for which surrogates were
      significantly more likely to choose treatment when patients would have them
      refuse. The findings can assist patients and clinicians in choosing a surrogate
      whose decision-making corresponds with patient choices.

PMID- 7622167
TI  - Development of the perceptions of racism scale.
AB  - Racism may be a factor in low-birth-weight (LBW) and preterm delivery in African
      American childbearing women. Because no satisfactory measure of racism existed,
      the Perception of Racism Scale (PRS) was developed. The PRS was pilot tested on
      109 participants from churches and community organizations. The scale was then
      used in a study of 136 childbearing women to investigate LBW and preterm
      delivery. Twenty items rated on a 4-point Likert-type scale were scored with 1 as
      the lowest and 4 as the highest perception of racism. Alpha reliabilities were
      .88 for the pilot and .91 for the study. Content validity was strengthened by
      expert panel critique. Reliability, content validity, and construct validity were
      demonstrated and no undue participant burden was observed. The scale is an
      effective instrument to measure perceptions of racism by African American women.

PMID- 7622168
TI  - Health diaries in nursing research and practice.
AB  - Health diaries have been used in research and clinical practice to examine the
      daily symptoms of healthy and ill people, responses to symptoms, and efficacy of
      symptom response. This article describes current uses of health diaries in
      nursing research and practice, the types of typical health diaries, factors
      affecting the quality of diary data, and the costs and analytic issues related to
      health diaries. The implications of health diaries for nursing education,
      practice, and research are considered.

PMID- 7622169
TI  - The need for well-prepared nurse administrators in long-term care.

PMID- 7622170
TI  - Analysis of restraint-free nursing homes.
AB  - Administrators and key informants in restraint-free nursing homes participated in
      a telephone survey to improve understanding of the process, resources, and
      measures for successful adoption of restraint-free care. Respondents expressed a
      strong opinion that each facility must develop its own individualized approach to
      restraint removal. However, similar approaches were found which suggest that
      efficiencies in conversion may be gained through application of change theory
      informed by restraint removal experience.

PMID- 7622171
TI  - Kudos to Page and Arena.

PMID- 7622172
TI  - A decent paying job--not art and beauty.

PMID- 7622173
TI  - Exercise and immunity.

PMID- 7622174
TI  - Nurses' effect on changing patient outcomes.
AB  - Emphasis on examining provider effects and resulting patient outcomes has grown
      considerably in the past several decades. This paper highlights the effect of
      nurses on changing patient outcomes. The most important issues raised include the
      types of patient outcomes that should be measured; the amount and type of nursing
      (or "nurse dose") needed to effect patient outcomes; the nurse dose needed in a
      given health care environment to demonstrate an effect; and the nurse dose needed
      for effects with differing patient groups.

PMID- 7622175
TI  - Evaluation of phagocytic capacity with a modified flow cytometry technique.
AB  - Phagocytic capacity was determined in human polymorphonuclear leukocytes with a
      modified flow cytometry technique. The advantages of this method include
      simplified sample preparation--the assay is done using whole blood--and
      quantification of phagocytosis with a phagocytic index obtained by comparison
      with controls, which obviates errors arising from non-specific adherence.

PMID- 7622176
TI  - Detection of Brucella antibodies in eluted dried blood: a validation study.
AB  - In order to develop a rapid method for the diagnosis of human brucellosis,
      results of the ELISA test performed on dried whole blood spotted on filter paper
      were compared with those of the same test carried out on the serum of the same
      160 subjects. Four patterns of elution were tested, combining incubation at 4
      degrees C with different exposure times in an ultrasound bath. The best
      correlation (r = 0.79) for the IgG test, was obtained by using a 12-h incubation
      period plus a 20-min ultrasonic exposure; the same incubation period without
      ultrasound produced the best correlation for the IgM test (r = 0.81).

PMID- 7622177
TI  - Antibody against interleukin-5 prevents antigen-induced eosinophil infiltration
      and bronchial hyperreactivity in the guinea pig airways.
AB  - Interleukin-5 (IL-5) induces proliferation, differentiation and activation of
      eosinophils. An animal model of local allergen (airways) sensitization was
      employed to study the effects of anti-IL-5 monoclonal antibody (mAb) on
      infiltration of eosinophils into inflammatory region, the development of antigen
      induced late asthmatic response (LAR) and the increased bronchial responsiveness
      following LAR. Guinea pigs exposed to aerosolized ovalbumin (OVA) daily for 10
      days developed an increase in the number of eosinophils in the tracheal wall 24 h
      after aerosolized OVA challenge. Furthermore, all animals developed an apparent
      LAR determined by the response with a 2-fold increase in respiratory resistance
      and showed an increase in bronchial responsiveness to acetylcholine 24 h after
      OVA challenge. In animals treated with anti-IL-5 mAb, however, eosinophil number
      in the tracheal wall dramatically decreased compared with animals treated with
      control antibody. The development of LAR was also remarkably suppressed by anti
      IL-5 mAb treatment, although a similar magnitude of immediate bronchoconstriction
      was observed. Moreover, in anti-IL-5 antibody-treated guinea pigs, an increase in
      bronchial responsiveness to acetylcholine significantly decreased. Data
      demonstrate that IL-5 is involved in airway eosinophilia, development of LAR and
      an increase in bronchial responsiveness induced by allergen sensitization via the
      airways. Development of IL-5 synthesis inhibitors and/or receptor antagonists
      could provide another therapeutic class of anti-asthmatic drugs.

PMID- 7622178
TI  - Functional alterations of human blood monocytes after exposure to various nickel
      compounds in vitro: an effect on the production of hydrogen peroxide.
AB  - It is generally known that nickel, a metal with distinct carcinogenic properties,
      can significantly alter the functioning of host defense mechanisms and impair
      various components of the immune system. In the present study the influence of 3
      nickel salts on the production of hydrogen peroxide (H2O2) by human monocytes was
      examined in in vitro culture. Highly purified, resting and PMA-stimulated normal
      human monocytes were cultured with subtoxic concentrations of nickel subsulfide
      nickel sulfate, nickel acetate and manganese chloride. A portion of the cells was
      cultured with nickel-manganese salt mixture. Following culture cells were tested
      in an in vitro functional assay for H2O2 production. It has been shown that all
      nickel salts, used in micromole concentrations, suppressed H2O2 formation both in
      resting and PMA-stimulated monocytes, while it was not the case when manganese
      chloride was used for cell cultures. The strongest suppressive effect was
      manifested by nickel sulfate. The cells subjected to nickel-manganese mixture
      displayed H2O2 production similar to that of control ones. These results show
      that nickel salts in micromole concentrations exert a suppressive effect on
      oxygen-dependent antimicrobial system of human monocytes and manganese prevents
      this effect.

PMID- 7622179
TI  - Identification of a cytolytic protein in the coelomic fluid of Eisenia foetida
      earthworms.
AB  - Total coelomic fluid of earthworms Eisenia foetida (Oligochaeta, Annelida) is
      capable of lysing different mammalian tumor cell lines. This cytolytic activity
      is different from tumor necrosis factor (TNF)-mediated lysis and is not due to
      proteolysis. Total coelomic fluid was subjected to ion-exchange chromatography
      separation and a fraction with prominent cytolytic activity was used to elicit
      monoclonal antibodies that were screened for their capacity to neutralize the
      cytolytic effect of total coelomic fluid. One of the prepared neutralizing IgG
      antibodies was used for the immunoaffinity purification of a cytolytic factor
      from total coelomic fluid. SDS-PAGE and Western blot analyses revealed a protein
      band with an apparent molecular weight of 42 kDa. This cytolytic protein (termed
      CCF-1 or coelomic cytolytic factor 1) can be adsorbed on the surface of opsonized
      particles and may be involved in opsonizing and hemolytic effects of coelomic
      fluid.

PMID- 7622180
TI  - Peptide motif of a cattle MHC class I molecule.
AB  - A consensus motif for a bovine major histocompatibility complex (MHC) class I
      molecule, A20, was derived from parainfluenza type-3 (PI-3) virus-infected muscle
      derived fibroblast cells and peripheral blood leukocytes by extraction of the
      naturally processed peptides from MHC class I molecules by treatment with TFA and
      peptide sequencing of the complex mixture. The results showed that the majority
      of peptides were 9 amino acids long with position 2 occupied by lysine and
      position 9 occupied by arginine. The arginine at position 9 suggests that cattle,
      like humans, but unlike the mouse have permissive TAP transporter molecules
      accepting peptides with positively charged amino acids at their C-terminus. This
      is the first report of a MHC ligand motif in cattle.

PMID- 7622181
TI  - Collagen induces cytokine production by synovial fluid mononuclear cells in
      rheumatoid arthritis.
AB  - Synovial fluid (SF) mononuclear cells (MNC) from 13 patients with rheumatoid
      arthritis (RA) and 12 patients with other arthritic diseases (OD) including
      osteoarthritis (OA), gout and spondyloarthritis (SA) were cultured in the
      presence of collagen types I and II or lipopolysaccharide (LPS) for 24 h.
      Interleukin-1 (IL-1), IL-6 and tumor necrosis factor-alpha (TNF-alpha) in the SF
      and culture supernatants were assayed using ELISA. The results showed that one
      half of the RA patients with high SF monocyte count had high SF IL-6 levels that
      coincided with the high spontaneous release of IL-6 by SF MNC. In the other RA
      patients with lower SF monocyte count, type II collagen induced significantly
      higher IL-1 beta than the medium control levels by SF MNC (P < 0.01) or that of
      the other diseases (P < 0.01). Similarly, type II collagen-induced IL-6 and TNF
      alpha production rose significantly (P < 0.01) from SF MNC of RA but less from OD
      (P < 0.05). In addition, type I collagen could also induce IL-1, IL-6 and TNF
      alpha in these samples from RA and OD patients but was less potent than type II
      collagen. Our results indicate that collagen-induced cytokines may be important
      in the pathogenesis of the disease.

PMID- 7622183
TI  - Nitric oxide production and mycobacterial growth inhibition by murine alveolar
      macrophages: the sequence of rIFN-gamma stimulation and Mycobacterium bovis BCG
      infection determines macrophage activation.
AB  - Prestimulation with recombinant-interferon-gamma (rIFN-gamma) followed by
      Mycobacterium bovis BCG infection induced high nitric oxide production and potent
      mycobacterial growth inhibition in murine alveolar macrophages. Reversal of the
      sequence of treatments caused opposite effects, suggesting that a sequential 2
      step process comprising first rIFN-gamma stimulation and second mycobacterial
      infection is operative in the activation of alveolar macrophages.

PMID- 7622182
TI  - The outer surface lipoprotein A of Borrelia burgdorferi provides direct and
      indirect augmenting/co-stimulatory signals for the activation of CD4+ and CD8+ T
      cells.
AB  - Naive CD4+ and CD8+ T cells require two distinct signals to proliferate and to
      express effector functions [1]. One is provided by the antigen receptor on the T
      cell (TCR) after its encounter with antigenic peptides associated with class I or
      II major histocompatibility complex (MHC) molecules on antigen-presenting cells
      (APC) [2]. The second signal, which is not antigen-specific but essential for
      proliferation and differentiation of naive T cells, is provided by co-stimulatory
      structures. The major co-stimulatory molecules for CD4+ T cells seem to be B7
      [3], B7.2 [4,5], and heat-stable antigen (HSA) [6]. These molecules are expressed
      on a variety of naive and/or activated APC and bind to CD28 and CTLA-4 and
      possibly other, as yet undefined, TCRs [3,7]. Optimal T cell activation only
      occurs when co-stimulatory molecules and ligands for the TCR are expressed on the
      same APC [8,9]. However, co-stimulation for T cells may also be provided via
      bystander cells [8,9] or by glycoproteins of the extracellular matrix, like
      fibronectin [10] and laminin [11]. In this case, T-cell VLA integrins function as
      signaling molecules [10,11]. This indicates that antigen-specific T-cell
      activation may also occur in areas where antigens are presented in association
      with extracellular matrix proteins. The recent finding that the invasion protein
      of Yersinia spp. delivers co-stimulatory signals to anti-CD3-activated human T
      cells, most probably through the b1 integrins, suggests that bacterial products
      can also bind to contribute to the activation of T cells [12].(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7622184
TI  - Stimulus-dependent production of cytokines and pterins by peripheral blood
      mononuclear cells.
AB  - The cytokine profiles produced by peripheral blood mononuclear cell (PBMC)
      cultures were dependent upon the nature of the stimulus used. Powerful lymphocyte
      activators such as mitogens induced rapid cell proliferation together with the
      production of both inflammatory (IL-1 alpha, IL-1 beta, IL-6 and TNF alpha) and
      immune (IFN-gamma, TNF-alpha and TNF-beta) cytokines, and immune activation
      markers (soluble IL-2 receptor, neopterin and xanthopterin). Bacterial endotoxin
      failed to induce cell proliferation but resulted in the rapid production of
      inflammatory cytokines together with a short burst of IFN-gamma production,
      without the production of the other immune cytokines or activation markers.
      Alloantigen stimulation gave a typical immune cytokine and marker profile, with
      little or no production of inflammatory cytokines. Re-call antigens (candida and
      PPD) induced maximal cell proliferation at days 5 to 6, but induced little or no
      production of inflammatory cytokines. Markedly different immune cytokine profiles
      were obtained with these re-call antigens. Candida induced an early burst of IFN
      gamma production on day 1 followed by later production of TNF-alpha. In cultures
      stimulated with PPD, both IFN-gamma and TNF-alpha were detected from day 2. With
      both re-call antigens, the levels of production of the activation markers were
      equivalent to the proliferative responses obtained.

PMID- 7622185
TI  - Induction of autoantibodies in normal mice by injection of nucleobindin and
      natural occurrence of antibodies against nucleobindin in autoimmune MRL/lpr/lpr
      mice.
AB  - Our previous works have shown that nucleobindin (Nuc) or recombinant (r) Nuc not
      only augments anti-DNA antibody production in vitro but also accelerates
      autoimmune response in vivo in MRL/+/+ (MRL/n) mice which are the substrain of
      autoimmune MRL/lpr/lpr (MRL/l) mice. To investigate whether rNuc can induce
      autoimmune response similarly in naive mice, we carried out intraperitoneal
      (i.p.) injection of rNuc (5 micrograms) without adjuvant into 8-week-old female
      BALB/c mice and continued injection twice a week for 12 weeks. About 5 weeks
      after the first injection, all the mice began to show IgG hypergammaglobulinemia
      (HG) followed by elevation of a number of autoantibodies of the IgG class such as
      anti-double-stranded (ds) DNA, anti-U1 ribonuclear protein (RNP), anti-ssB(La)
      and anti-Fc antibodies (RF), but not by anti-Sm antibodies. However, the IgG anti
      dsDNA antibody response and histopathological changes in the kidney of these
      BALB/c mice were not so noticeable as those in MRL/n mice induced by rNuc in our
      previous experiment. In contrast, the IgG anti-rNuc antibody response of normal
      BALB/c mice induced by rNuc was stronger than that of MRL/n mice induced by rNuc.
      Since the titers of each autoantibody of BALB/c mice induced by rNuc were not
      always associated with the level of IgG HG, and either IgG HG or IgG
      autoantibodies could not be induced by control administration of extracts (5
      micrograms) of Escherichia coli with or without harboring plasmid alone,
      polyclonal B cell activation (PBA) appeared not to be the mechanism of this
      autoimmunity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7622186
TI  - Synergism of IL-3, IL-5, and GM-CSF on eosinophil differentiation and its
      application for an assay of murine IL-5 as an eosinophil differentiation factor.
AB  - In order to elucidate the mechanisms of eosinophil differentiation, we examined
      the effects of combinations of interleukin 5 (IL-5) with IL-3 and granulocyte
      macrophage colony-stimulating factor (GM-CSF) on in vitro differentiation into
      eosinophils from bone marrow cells of ICR mice. When the amount of added IL-5 was
      kept constant, IL-3 exhibited dose-dependent production of eosinophils both in
      the absence and presence of low doses of GM-CSF. In contrast, IL-5 plus GM-CSF
      showed highly enhanced production of eosinophils, and eosinophil production
      maximized at a concentration between 10 and 20 U/ml and decreased at higher
      concentrations. When IL-3 and GM-CSF were kept constant at concentrations of 20
      U/ml and 10 U/ml, respectively, the number of eosinophils increased linearly in
      IL-5-dependent manner in a range from 0.3 to 30 U/ml. These results suggest that
      IL-3 and GM-CSF act synergistically with IL-5 in in vitro eosinophil
      differentiation. In addition, we propose a new method for quantifying eosinophil
      differentiation activity of IL-5.

PMID- 7622188
TI  - Immunosuppressive factor from liver induces apoptosis in thymoma EL-4 cells but
      not normal MHC class II-specific T lymphocytes.
AB  - An endogenously produced immunosuppressive factor (ISFnp, immunosuppressive
      factor-neutral protein), inducing a decrease in viability of thymoma EL-4 cells
      in vitro, was isolated from murine liver using ion exchange, gel filtration and
      hydrogen-bonding chromatography. Polyclonal rabbit antibodies against this factor
      were developed and attached to periodate-activated Sepharose CL-6B. The
      immunoaffine sorbent obtained significantly depleted the biological activity of
      ISFnp from tested fractions. The factor shows liver-specific location, an M(r) of
      about 70-80 kDa and consists of 2 subunits (40 and 42 kDa) as determined by SDS
      PAGE and Western blotting. ISFnp induced DNA degradation in EL-4 cells similar to
      the cleavage of DNA onto olygonucleosomal fragments in dexamethasone-treated
      thymocytes. This DNA degradation preceded lysis of thymoma cells, suggesting an
      induction of apoptosis in ISFnp-treated EL-4 cells. Addition of the factor into
      primary mixed lymphocyte culture (MLC) strongly inhibited proliferative response
      but failed to induce any decrease in the ability of normal MHC class II-specific
      alloreactive cells to respond in the secondary MLC. Moreover, addition of ISFnp
      into primary MLC on the peak of proliferative response resulted in augmentation
      of secondary responses of primed cells as compared with the same quantities of
      primed cells from untreated cultures. These results suggest a possible role of
      liver both in deletion of transformed clones of T lymphocytes and formation of
      allospecific memory T cells.

PMID- 7622187
TI  - Functional role of CD26 on human B lymphocytes.
AB  - CD26 is a well-known activation marker on T cells and natural killer (NK) cells
      [1]. It is identical with the ectopeptidase dipeptidyl peptidase IV (DP IV). The
      expression of CD26 on B cells has been discussed controversially [2,3]. We have
      studied the expression of this enzyme on B cells from the peripheral blood of
      healthy donors and of CVID patients, on cells of the Daudi Burkitt line and the
      EBV-transformed B-cell lines Jojo and Laz509. DP IV was detected by using anti
      CD26 monoclonal antibodies and with help of specific enzyme substrates. Further
      the influence of specific synthetic DP IV inhibitors on mitogenic activation of
      purified B cells and DNA synthesis of cell lines was studied. We could show that
      in both groups 0-5% of freshly isolated CD20-positive B cells do express the CD26
      antigen. After stimulation with pokeweed mitogen or St. aureus protein, the
      fraction of CD26-positive cells was enhanced up to 51% and 36%, respectively.
      Interestingly, induction of CD26 expression on B cells from CVID patients occurs
      in a manner similar to the B cells from healthy donors. Treatment of peripheral
      blood B cells and B-cell lines with highly specific competitive DP IV inhibitors
      leads to a significant inhibition of DNA synthesis in a dose-dependent manner.
      These data show that CD26 can be considered to be an activation marker not only
      of T- and NK cells but also of a main population of B cells, suggesting an
      involvement of CD26 in B-cell activation.

PMID- 7622189
TI  - Outcome of infection with different strains of Trypanosoma cruzi in mice lacking
      CD4 and/or CD8.
AB  - Mice lacking CD4 and/or CD8 gene expression, generated by embryonic stem-cell
      technology, were used to study the role of CD4+ and CD8+ cells in the resistance
      to the acute infection with virulent (Tulahuen and RA) or mild (CA-I) strains of
      Trypanosoma cruzi. The presence of both CD4+ and CD8+ cells contributed to the
      survival of mice infected with T. cruzi, and each T-cell subtype was able to
      sustain protective functions in the absence of the other one. However, in certain
      host-parasite combinations, CD8+ cell-independent mechanisms were able to control
      the parasite load. Moreover, CD8- mice chronically infected with a low virulent
      strain of T. cruzi were protected from an otherwise lethal challenge with the
      parasite. A different organ distribution of parasite nests was observed when
      mutant (but not wild type) animals infected with different parasite strains were
      compared. CD4- mice produced high levels of IgG antibodies against peptide
      antigens or a whole homogenate from the parasite after infection with CA-I
      strain. A dramatic enhancement of IgG1- and IgG2a-specific antibodies was
      observed.

PMID- 7622191
TI  - Thapsigargin induces IL-2 receptor alpha-chain in human peripheral and Jurkat T
      cells via a protein kinase C-independent mechanism.
AB  - Thapsigargin (TG), an inhibitor of Ca(2+)-ATPase, depletes intracellular Ca2+
      stores and induces a sustained Ca2+ influx without altering phosphatidyl inositol
      levels. TG plus phorbol myristate acetate (PMA) but not TG alone induced IL-2 in
      Jurkat T cells, suggesting that TG had no effect on protein kinase C (PKC).
      However, TG induced increases in IL-2R alpha protein as well as IL-2R alpha mRNA
      in Jurkat T cells in a dose-dependent manner. A similar increase in IL-2R alpha
      by TG was also observed in human peripheral T cells. Further, like PMA, TG
      markedly induced NF kappa B in Jurkat T cells. However, TG and PMA exhibited a
      synergistic action on IL-2R alpha expression, suggesting that TG and PMA induce
      IL-2R alpha through distinct pathways. PMA- but not TG-induced IL-2R alpha is
      inhibited by the PKC inhibitor H7, whereas TG- but not PMA-induced IL-2R alpha
      was inhibited by cholera toxin, forskolin and 1,9-dideoxy forskolin. In toto,
      these results suggest that TG induces IL-2R alpha in human T cells through a PKC
      independent pathway.

PMID- 7622190
TI  - Characterization of human homologue of 4-1BB and its ligand.
AB  - The human homologue of 4-1BB (H4-1BB) cDNA was isolated from PMA plus ionomycin
      treated human peripheral T-cell cDNA libraries. The amino acid sequence deduced
      from the nucleotide sequence showed that the protein is composed of 255 amino
      acids with 2 potential N-linked glycosylation sites. The molecular weight of its
      protein backbone is calculated to be 27 kDa. The H4-1BB contains features such as
      signal sequence and transmembrane domain, indicating that it is a receptor
      protein. This protein showed 60% identity of amino acid sequence to mouse 4-1BB.
      In the cytoplasmic domain there are 5 regions of amino acid sequences conserved
      from mouse to human, indicating that these residues might be important in the 4
      1BB function. H4-1BB mRNA was detected in unstimulated peripheral blood T cells
      and was inducible in T-cell lines such as Jurkat and CEM. H4-1BB-AP, a fusion
      protein between the H4-1BB extracellular domain and alkaline phosphatase, was
      used to identify the ligand for the H4-1BB. Although the H4-1BB ligand was
      detected in both T and B cells of human peripheral blood, the ligand was
      preferentially expressed in primary B cells and B-cell lines. Daudi, a B-cell
      lymphoma, was one of the B-cell lines that carried a higher number of ligands.
      Scatchard analysis showed that the Kd = 1.4 x 10(9) M and the number of ligands
      in Daudi cell was 4.2 x 10(3).

PMID- 7622192
TI  - A monoclonal antibody to an ovine gp130 molecule inhibits homotypic aggregation
      induced by anti-CD43 monoclonal antibodies of ruminant leukocytes.
AB  - A monoclonal antibody (mAb) Co.3E1D4 which recognized a molecule present on the
      surface of ovine peripheral blood granulocytes, monocytes, platelets and a small
      percentage of lymphocytes, was able to block leukocyte aggregation induced by
      mAbs specific for the leukosialin or CD43 molecule. Co.3E1D4 precipitated an
      antigen with apparent molecular weight of 130 kDa (under reducing and non
      reducing conditions). Endoglycosidase F digestion of the molecule resulted in
      reduction in the apparent molecular weight. These data suggest that the antigen
      recognized by Co.3E1D4 may be homologous to the human CD31 or platelet
      endothelial cell adhesion molecule-1 (PECAM-1). Aggregation produced by other
      inducers such as PMA was not blocked showing that only some cell-cell
      interactions were mediated by the gp130 molecule.

PMID- 7622193
TI  - Interferon-gamma but not granulocyte/macrophage colony-stimulating factor
      augments proteoglycan presentation by synovial cells and chondrocytes to an
      autopathogenic T cell hybridoma.
AB  - Immunization of BALB/c mice with human cartilage proteoglycan (aggrecan) produces
      a progressive polyarthritis, similar in many aspects to human rheumatoid
      arthritis, and autoreactive T cells are necessary for initiation of the disease.
      To study the immunopathological mechanisms operating in the synovium of arthritic
      mice, we isolated a proteoglycan (PG)-specific arthritogenic T-cell hybridoma,
      5/4E8, and examined the presentation of PG to this T-cell hybridoma by mouse
      synovial cells and chondrocytes. Both cell types expressed very low levels of
      major histocompatibility complex (MHC) class II following isolation and culture
      and were unable to present PG to the hybridoma. However, following stimulation
      with interferon-gamma (IFN-gamma), both synovial cells and chondrocytes showed a
      marked increase in MHC class II expression and consequently were able to present
      PG very effectively. The PG-specific responses of the hybridoma were abrogated by
      an anti-Ia monoclonal antibody. Granulocyte-macrophage colony-stimulating factor
      (GM-CSF), one of the most abundant cytokines in the rheumatoid synovium, had no
      effect on the antigen-presenting capacity of synovial cells and chondrocytes,
      either on its own or together with IFN gamma.

PMID- 7622194
TI  - Defective interleukin-2 R gene expression in gastric carcinoma patients.
AB  - Peripheral blood T lymphocytes from 15 patients with gastric carcinoma and 6
      normal healthy controls were evaluated for Interleukin-2 R gene expression. Total
      RNA was extracted from T cell-enriched fractions of patients as well as from
      control peripheral blood lymphocytes, with or without mitogenic stimulation. The
      presence of mRNA for IL-2 R alpha evaluated by Northern blot analysis revealed
      that unstimulated T cells expressed lower levels of IL-2 R mRNA than PHA
      stimulated T cells. Expression of both IL-2 R alpha transcripts (3.5 and 1.5 Kb)
      were either not detectable or only weakly detectable on T lymphocytes from
      patients even after mitogenic stimulation. In contrast, a significant rise in the
      expression of both IL-2 R alpha transcripts was observed on T cells from normal
      controls followed by mitogenic challenge. This paper reports on the defective IL
      2 R alpha gene expression in gastric carcinoma patients, which may explain one of
      the causes of immunodeficiency associated with neoplastic transformation and
      progression.

PMID- 7622195
TI  - I-45 islet cell antigen is a 68kD neuroendocrine protein.
AB  - A monoclonal antibody approach was used to characterize islet cell
      differentiation antigens involved in autoimmunity related diabetes mellitus. This
      procedure yielded islet cell monoclonal antibodies (ICMAbs) that demonstrated
      varying tissue/cellular distribution. The ICMAb I-45 showed a pan-islet
      reactivity similar to the reactivity of islet cell autoantibodies. The target
      antigen of the ICMAb I-45 demonstrated a neuroendocrine distribution. Single step
      immunoaffinity purification of I-45 antigen using I-45 monoclonal antibody
      immunoaffinity matrix yielded a 68kD protein. The specificity of the
      immunoaffinity purified 68kD protein was further demonstrated by the lack of
      binding of this protein to immunoaffinity columns of irrelevant monoclonal
      antibodies. The neuroendocrine distribution of the I-45 antigen, like that of
      other differentiation molecules like HISL-19, neuron specific enolase and
      chromogranin A strengthens the hypothesis of neuroectodermal origin of the islets
      of Langerhans.

PMID- 7622196
TI  - Administration of dehydroepiandrosterone reverses the immune suppression induced
      by high dose antigen in mice.
AB  - Several factors including antigen concentration, the route of antigen
      administration, hormones and cytokines have shown to affect T cells to produce
      the distinct patterns of lymphokines which exert regulatory and effector
      functions of immune response. In this study, we asked whether administration of
      dehydroepiandrosterone (DHEA) to mice which were tolerized by high dose of
      antigen could modulate T cell functions to restore the suppressed cellular immune
      response and to produce the distinct lymphokines. An intravenous injection of
      high dose of sheep red blood cells induced suppression of delayed type
      hypersensitivity (DTH) and a single subcutaneous injection of the tolerant mice
      with DHEA restored the suppressed DTH response. Furthermore, in vitro treatment
      of spleen cells from tolerant mice with DHEA abolished the transfer of tolerance
      to naive recipients. Lymphocytes from the DHEA-treated tolerant mice produced
      more IFN-gamma and less IL-4 and IL-6 than the cells from tolerant animals
      without DHEA treatment. These findings indicate that DHEA could recover antigen
      specific immune suppression by differentially affecting T cells to produce the
      distinct lymphokines.

PMID- 7622197
TI  - Accumulation of gamma/delta T cells in human dysgerminoma and seminoma: roles in
      autologous tumor killing and granuloma formation.
AB  - The precise biological function of a subset of T cells bearing gamma/delta T cell
      receptor (TCR) remains poorly understood. The present study demonstrated the
      presence of gamma/delta T cells in tumor-infiltrating lymphocytes (TIL) and
      peripheral blood lymphocytes (PBL) of human patients with dysgerminoma and
      seminoma when determined by flow cytometry and in situ immunohistochemical
      staining. TIL contained a high percentage of gamma/delta T cells, ranging from
      17.3 to 35.1%. gamma/delta T cells often accumulated within the granulomatous
      inflammation of tumor tissues. The majority of gamma/delta T cells were V gamma
      9/V delta 2+ cells. Freshly isolated PBL, TIL and purified gamma/delta T cells
      showed autologous tumor killing (ATK) activity, which could be inhibited by
      monoclonal antibodies (mAb) against V delta 2. Furthermore, two gamma/delta T
      cell clones established from TIL showed cytotoxicity against autologous and
      allogeneic dysgerminoma, while they had low or no lytic effects on other cell
      types including carcinomas of ovary and tumor cell lines such as K562, Daudi and
      Molt-4. Lysis of autologous tumor cells by the clone was inhibited completely by
      anti-V delta 2 mAb and partially by mAb against CD3, LFA-1 alpha and ICAM-1
      molecules, while it was resistant to anti-CD8, anti-HLA-ABC and anti-HLA-DR mAb.
      Supernatants produced by gamma/delta T cell clones induced adhesion, aggregation
      and increased DNA synthesis of monocytes and some characteristics of activated
      macrophages or epithelioid cells. Tumor necrosis factor (TNF)-alpha, granulocyte
      macrophage colony stimulating factor (GM-CSF) and interferon (IFN)-gamma were
      detected in the supernatants of gamma/delta T cell clone. These results suggest
      that gamma/delta T cells accumulating in dysgerminoma and seminoma exhibit ATK
      activity through V gamma 9/delta 2 TCR and these gamma/delta T cells also play a
      role in the formation of granulomatous inflammation, which is associated with
      human dysgerminoma and seminoma.

PMID- 7622198
TI  - Modulation of the functions of dengue virus-specific human CD8+ cytotoxic T cell
      clone by IL-2, IL-7 and IFN gamma.
AB  - Lymphokines play an important role in immune responses to viruses by modulating
      functions of T lymphocytes. In the present study, we examined the effects of
      interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-7
      (IL-7), and interferon gamma (IFN gamma) on proliferation, cytotoxic activity and
      lymphokine production of a dengue virus-specific CD8+ human cytotoxic T
      lymphocyte (CTL) clone. IL-2 and IL-7 induced proliferation of the CD8+ CTL clone
      in the presence or absence of specific antigen, while IFN gamma suppressed
      proliferation of the clone. IL-7 and IFN gamma augmented dengue virus-specific
      cytotoxic activity without inducing non-specific cytotoxic activity, and IL-2
      induced non-specific cytotoxic activity. IL-2 induced IFN gamma production by the
      CD8+ CTL clone. IL-4 and IL-6 did not modulate the functions of the CD8+ CTL
      clone in these experimental conditions. These results suggest that functions of
      dengue virus-specific CD8+ CTL are modulated by IL-2, IL-7 and IFN gamma, and
      that IL-7 is a lymphokine useful to induce growth and to maintain specific
      cytotoxic activity of CD8+ CTL clones in vitro.

PMID- 7622199
TI  - Homogenous IgA monomers, dimers, trimers and tetramers from the same IgA myeloma
      serum.
AB  - Starting from two IgA1 myeloma sera, the isolation of monoclonal monomeric,
      dimeric, trimeric and tetrameric IgA in a high state of purity and size
      homogeneity for each serum is described. The method combined repetitive gel
      filtrations on Ultrogel AcA22 with affinity chromatography on Jacalin-Sepharose.
      These various forms of pure polymeric IgA obtained from the same monoclonal IgA
      should allow a precise comparison of their respective structure and reactivity
      with different IgA-binding proteins, such as IgA Fc-receptors, the polymeric Ig
      receptor, and lectins.

PMID- 7622200
TI  - Suppression of immune parameters in animal models of morphine dependence.
AB  - Implantation of pellets containing 75 mg of morphine induced short term (4 day)
      morphine dependence and markedly reduced total number of spleen cells of BALB/c
      mice, without affecting total body or liver weight. Polyclonal responses induced
      by anti-CD3 antibodies, Concanavalin A or Escherichia coli lipopolysaccharide in
      the remaining spleen cells of morphine-treated mice were also inhibited.
      Cytofluorimetric analysis indicated that the proportion of major functional
      lymphocyte populations (Ig+, CD3+, CD4+ and CD8+ lymphocytes) were not
      significantly changed in the spleen from morphine-dependent mice. Furthermore,
      expression levels of surface Ig, CD3, CD4, and CD8, were similar in spleen cells
      from control or morphine-treated mice. So, morphine dependence in BALB/c mice
      under these controlled conditions results in a specific defect in lymphoid cell
      number and function, with no incidence on body weight or particular lymphocyte
      subsets.

PMID- 7622201
TI  - Borrelia burgdorferi shows specificity of binding to glycosphingolipids.
AB  - Live but not fixed or heat-killed Borrelia burgdorferi bound to
      galactocerebroside, lactosylceramide, and ceramide trihexoside. In addition, this
      organism bound to the disialoganglioside GD1a and the trisialoganglioside GT1b
      but not to gangliosides GM1, GD1b, GM2, and GM3 and not to asialo GM1. This
      adhesion pattern confirmed earlier findings of binding to galactocerebroside and
      places this organism within a prokaryotic group which binds to lactosylceramide.
      The binding to GD1a and GT1b, both of which carry terminal as well as multiple
      sialic acids, indicates that B. burgdorferi can show specificity of binding
      within a group of acidic gangliosides. Adhesion could not be inhibited by several
      concentrations of sugars and sialic acid, indicating more complex binding
      requirements than for terminal carbohydrates alone. Low-passage strains adhered
      to the four substrates in greater numbers than strains in culture for long
      periods of time. OspB mutants in general bound better or at least equally well to
      several of the glycosphingolipids, and preincubation of substrates with soluble
      recombinant and affinity-purified Osp did not inhibitor or weakly inhibited the
      binding of the organisms. These findings suggest that outer surface lipoproteins
      A and B are not directly involved in adhesion to glycosphingolipids.

PMID- 7622202
TI  - A natural mutation of the amino acid residue at position 60 destroys
      staphylococcal enterotoxin A murine T-cell mitogenicity.
AB  - A variety of techniques have been used to identify the amino acid residues of
      bacterial superantigens involved in their interactions with major
      histocompatibility complex (MHC) class II and T-cell receptor (TCR). In this
      study, we isolated a naturally mutated staphylococcal enterotoxin A (SEA) from
      three different Staphylococcus aureus strains, in which the amino acid at
      position 60 has been changed from aspartic acid (D) to asparagine (N). We then
      studied the influence of this change on the immunological activities of SEA. Our
      results demonstrated that this mutation does not affect the capacity of SEA to
      bind MHC class II molecules and consequently activates human monocytes and
      peripheral blood lymphocytes. In contrast, mutated SEA failed to stimulate the
      proliferation of murine splenic lymphocytes of two different strains, and when
      presented by human MHC class II molecules, it also failed to activate murine cell
      line 3DT, which expresses the SEA-specific TCR V beta element (V beta 1). These
      results indicate that this mutation alters the interaction between SEA and murine
      TCR. The reactivity patterns of the mutated SEA with two specific anti-SEA
      monoclonal antibodies suggested that the observed effect of the isolated mutation
      in the murine system might be due to certain conformational changes in the SEA
      molecule introduced upon changing the D at position 60 to N. Site-directed
      mutagenesis of the N residue to D or to glycine reconstituted the ability of SEA
      to stimulate murine splenic lymphocytes. The different effects of this natural
      mutation at position 60 on the immunological activities of SEA with murine and
      human cells highlight the relevance of the affinity and avidity in SEA-TCR
      interactions in the function of different species or may reflect a difference in
      epitope specificity.

PMID- 7622203
TI  - Characterization of a Legionella micdadei mip mutant.
AB  - The pathogenesis of Legionella micdadei is dependent upon its ability to infect
      alveolar phagocytes. To better understand the basis of intracellular infection by
      this organism, we examined the importance of its Mip surface protein. In
      Legionella pneumophila, Mip promotes infection of both human macrophages and
      freshwater protozoa. Southern hybridization and immunoblot analyses demonstrated
      that mip sequences were present and expressed within a panel of virulent L.
      micdadei strains. Using allelic exchange mutagenesis, we then constructed an L.
      micdadei strain that completely and specifically lacked Mip. Although unimpaired
      in its ability to grow in bacteriologic media, this Mip mutant was defective in
      its capacity to infect U937 cells, a human macrophage-like cell line. Most
      significantly, the Mip- organism displayed a 24-fold reduction in survivability
      immediately after its entry into the phagocyte. Similarly, the mutant was less
      able to parasitize Hartmannella amoebae. Taken together, these data argue that
      Mip specifically potentiates intracellular growth by L. micdadei.

PMID- 7622205
TI  - Active immunization with recombinant V antigen from Yersinia pestis protects mice
      against plague.
AB  - The gene encoding V antigen from Yersinia pestis was cloned into the plasmid
      expression vector pGEX-5X-2. When electroporated into Escherichia coli JM109, the
      recombinant expressed V antigen as a stable fusion protein with glutathione S
      transferase. The glutathione S-transferase-V fusion protein was isolated from
      recombinant E. coli and cleaved with factor Xa to yield purified V antigen as a
      stable product. Recombinant V antigen was inoculated intraperitoneally into mice
      and shown to induce a protective immune response against a subcutaneous challenge
      with 3.74 x 10(6) CFU of virulent Y. pestis. Protection correlated with the
      induction of a high titer of serum antibodies and a T-cell response specific for
      recombinant V antigen. These results indicate that V antigen should be a major
      component of an improved vaccine for plague.

PMID- 7622204
TI  - Evidence for glycosylation sites on the 45-kilodalton glycoprotein of
      Mycobacterium tuberculosis.
AB  - The occurrence of glycosylated proteins in Mycobacterium tuberculosis has been
      widely reported. However, unequivocal proof for the presence of true glycosylated
      amino acids within these proteins has not been demonstrated, and such evidence is
      essential because of the predominance of soluble lipoglycans and glycolipids in
      all mycobacterial extracts. We have confirmed the presence of several putative
      glycoproteins in subcellular fractions of M. tuberculosis by reaction with the
      lectin concanavalin A. One such product, with a molecular mass of 45 kDa, was
      purified from the culture filtrate. Compositional analysis demonstrated that the
      protein was rich in proline and that mannose, galactose, glucose, and arabinose
      together represented about 4% of the total mass. The 45-kDa glycoprotein was
      subjected to proteolytic digestion with either the Asp-N or the Glu-C
      endopeptidase or subtilisin, peptides were resolved by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis, and glycopeptides were identified by reaction
      with concanavalin A. Peptides were further separated, and when they were analyzed
      by liquid chromatography-electrospray mass spectrometry for neutral losses of
      hexoses (162 mass units), four peptides were identified, indicating that these
      were glycosylated with hexose residues. One peptide, with an average molecular
      mass of 1,516 atomic mass units (AMU), exhibited a loss of two hexose units. The
      N-terminal sequence of the 1,516-AMU glycopeptide was determined to be DPEPAPPVP,
      which was identical to the sequence of the amino terminus of the mature protein,
      DPEPAP PVPXTA. Furthermore, analysis of the glycopeptide by secondary ion mass
      spectrometry demonstrated that the complete sequence of the glycopeptide was
      DPEPAPPVPTTA. From this, it was determined that the 10th amino acid, threonine,
      was O-glycosidically linked to a disaccharide composed of two hexose residues,
      probably mannose. This report establishes that true, O-glycosylated proteins
      exist in mycobacteria.

PMID- 7622206
TI  - A novel synthetic lipid A analog with low endotoxicity, DT-5461, prevents lethal
      endotoxemia.
AB  - Bacterial endotoxin (lipopolysaccharide [LPS]) causes severe damage to the host
      organism as a result of excessive release of inflammatory cytokines, including
      interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF-alpha), from
      mononuclear phagocytes during gram-negative bacterial infection. We evaluated the
      ability of a novel synthetic lipid A analog with low endotoxicity, DT-5461, to
      antagonize LPS-induced IL-1 and TNF-alpha production in cells of
      monocyte/macrophage lineage and examined the protective effect of DT-5461 against
      lethal endotoxic shock in mice. The IL-1- or TNF-alpha-inducing activity of DT
      5461 is 100,000 to 10,000 times less active than that of Escherichia coli LPS
      (EcLPS) or synthetic lipid A. DT-5461 significantly inhibited EcLPS-induced IL-1
      and TNF-alpha release when murine peritoneal macrophages were incubated with DT
      5461 2 h prior to EcLPS stimulation at the same concentration (1 microgram/ml).
      The antagonistic effect of DT-5461 on the production of IL-1 and TNF-alpha
      induced by EcLPS occurred in a concentration-dependent manner. DT-5461 also
      inhibited IL-1 and TNF-alpha induction when murine peritoneal macrophages were
      stimulated by LPS from Salmonella typhimurium or synthetic lipid A, as well as by
      EcLPS, but not by muramyl dipeptides. This indicated that DT-5461 specifically
      antagonized the action of LPS. DT-5461 also antagonized EcLPS-mediated activation
      of human peripheral blood monocytes. DT-5461 blocked the binding of fluorescein
      isothiocyanate-labelled LPS to murine peritoneal macrophages as well as it did
      the binding of EcLPS and synthetic lipid A, i.e., in a concentration-dependent
      fashion. Injection of DT-5461 2 h before EcLPS challenge prevented the production
      of serum IL-1 and TNF-alpha in D-galactosamine-treated mice. Furthermore, this
      treatment modality protected mice against LPS-induced lethal toxicity. This study
      suggests that DT-5461 possesses a potent LPS antagonistic effect and may be
      useful in a protective strategy against lethal endotoxemia caused by gram
      negative bacterial infection.

PMID- 7622207
TI  - Impaired human responses to tetanus toxoid in vitamin A-deficient SCID mice
      reconstituted with human peripheral blood lymphocytes.
AB  - Vitamin A deficiency is associated with increased childhood morbidity and
      mortality from respiratory and diarrheal diseases. In order to evaluate the
      effect of vitamin A on human antibody responses, we developed a vitamin A
      deficient severe combined immunodeficient (SCID) mouse model. Vitamin A-deficient
      mice were produced by depriving them of vitamin A at day 7 of gestation. Mice
      were reconstituted with human peripheral blood lymphocytes (huPBL) from tetanus
      toxoid immune donors at 6 weeks of age and immunized with tetanus toxoid at 6 and
      8 weeks of age. Secondary human antibody responses were determined 10 days later.
      The geometric mean human anti-tetanus toxoid immunoglobulin G concentrations were
      3.75 micrograms/ml for the deficient mice and 148 micrograms/ml for controls (P =
      0.0005). Vitamin A-deficient mice had only a 2.9-fold increase in human anti
      tetanus toxoid antibody compared with a 74-fold increase in controls (P < 0.01).
      Supplementation with vitamin A prior to reconstitution restored human antibody
      responses to normal. These data suggest that vitamin A deficiency impairs human
      antibody responses. We speculate that impaired responses could increase
      susceptibility to certain infections. Furthermore, we propose that effects of
      other nutritional deficiencies on the human immune system could be evaluated in
      the SCID-huPBL model.

PMID- 7622208
TI  - Antibodies raised against the outer membrane protein interrupt adherence of
      enteroaggregative Escherichia coli.
AB  - Enteroaggregative Escherichia coli (EAggEC) is a distinct category of diarrheal
      pathogen implicated as the cause of persistent diarrhea. The pathogen exhibits a
      characteristic "stacked-brick" pattern of aggregation when incubated with HEp-2
      cells. The outer membrane protein (OMP) profile of a prototype EAggEC strain
      (F03) reflected the presence of one major 30-kDa protein. The OMP is expressed in
      the presence of the 60-MDa plasmid that the strain harbors. Antibodies were
      raised against the OMP by injecting the protein into a rabbit. The manifestation
      of an adherence phenotype on HEp-2 cells was observed for F03 and other strains
      that express OMP in the presence and absence of anti-OMP serum. Clumps of
      bacteria forming an aggregative pattern were observed in the HEp-2 cell assay in
      the absence of OMP antibodies, whereas a few bacteria attached to the cells in
      the presence of OMP antibodies. Mannose-resistant hemagglutination of human
      erythrocytes observed in the presence of EAggEC strains was inhibited in the
      presence of anti-OMP serum. Sequence analysis of a peptide generated by protease
      digestion of OMP exhibited 90% homology to a peptide of flagellin protein encoded
      by the hag gene of Serratia marcescens. Immunolabeling of the outer membrane by
      colloidal gold confirmed the protein to be an OMP. Our results suggest that the
      OMP of EAggEC have common antigenic properties. Antibodies raised against the
      protein can prevent adherence in vitro and could potentially interrupt the
      natural disease.

PMID- 7622209
TI  - Morphology of defensin-treated Staphylococcus aureus.
AB  - Defensins are a family of broad-spectrum antimicrobial peptides found abundantly
      in the cytoplasmic granules of mammalian neutrophils and Paneth cells of the
      small intestine. Defensins are known to form ion channels on the membranes of
      target cells. These channel formations and the cytotoxicity of defensins are
      intimately linked. We showed the morphological effects of defensins on the
      cytoplasmic membranes of Staphylococcus aureus by transmission electron
      microscopy. S. aureus exposed to defensins developed characteristic mesosome-like
      structures but did not show remarkable changes in cell walls. Defensins induced
      such structural changes not only at high concentration but also at low
      concentrations that were not bactericidal. We also showed that increasing the
      concentration of NaCl in the reaction mixture completely inhibited the occurrence
      of membranous changes of target cells exposed to defensins. These findings are,
      to our knowledge, the first report of morphological changes in gram-positive
      bacteria treated with defensins. Our results indicate that the first effect of
      defensins in S. aureus is to damage cytoplasmic membranes directly; they also
      support previous reports that the cell membrane is the principal target of
      defensins.

PMID- 7622211
TI  - Capsular polysaccharide-protein conjugate vaccines of carbotype 1 Vibrio
      vulnificus: construction, immunogenicity, and protective efficacy in a murine
      model.
AB  - Vibrio vulnificus causes septicemia and wound infections in immunocompromised
      humans. The capsular polysaccharide of Vibrio vulnificus (VvPS) is critical for
      virulence. We synthesized conjugate vaccines of carbotype 1 VvPS under conditions
      and in formulations suitable for human use. Purified VvPS was conjugated to
      tetanus toxoid (TT) or to inactivated V. vulnificus cytolysin or elastase by two
      different schemes. All conjugates elicited elevated anticapsular immunoglobulin G
      (IgG) and IgM and antiprotein IgG responses in mice compared with saline placebo.
      The conjugates prepared through caboxyl activation of VvPS (VvPS-TTa, VvPS
      cytolysin, and VvPS-elastase) were more immunogenic than the one prepared through
      hydroxyl activation (VvPS-TTb). The protective efficacy of conjugated and
      unconjugated formulations of VvPS and that of protein carriers were evaluated in
      a mouse septicemia model. Eighty percent of mice actively immunized with VvPS-TTa
      vaccine survived challenge with carbotype 1 V. vulnificus, while VvPS-cytolysin
      and VvPS-elastase conjugates conferred 44 and 40% protection, respectively.
      Control mice immunized with VvPS, cytolysin, or elastase alone, or saline only,
      showed 70 to 100% mortality. VvPS-TTa vaccine is nontoxic, immunogenic, and
      protective in mice.

PMID- 7622210
TI  - Fine specificity of the genetically controlled immune response to native and
      recombinant gp15/400 (polyprotein allergen) of Brugia malayi.
AB  - Polyprotein allergens are a family of structurally homologous molecules from
      parasitic nematodes which induce specific immunoglobulin E in infected
      individuals. We show here that both H-2 and non-H-2 factors determine the ability
      of mice to generate T- and B-cell responses to the filarial polyprotein allergen
      (Brugia malayi gp15/400). Further, H-2 and non-H-2 genes can complement one
      another to overcome nonresponsiveness to this molecule. However, these genetic
      restrictions govern only responses to the native glycoprotein and all strains of
      mice respond equivalently when immunized with a recombinant polypeptide.
      Overlapping fragments of gp15/400 were constructed to compare the T-cell and
      antibody responses to native versus recombinant gp15/400 in responder (BALB/c H
      2d) and nonresponder (B10.D2 H-2d, CBA H-2k, and BALB.K H-2k) strains. BALB/c
      mice generated T-cell responses to the same fragment (positions 89 to 133 and 1
      to 21) whether immunized with native or recombinant material, although the
      antibody responses differed in fine specificity, H-2k mice, unresponsive to the
      native molecule, generated T cells responsive to the centrally located peptide
      (positions 57 to 100) only when immunized with the recombinant. Antibody
      responses in H-2k mice were directed at the peptide (positions 11 to 67) which is
      glycosylated in the native molecule. Our findings suggest that recognition of
      gp15/400 is affected by modifications that occur in the parasite but are absent
      when the molecule is produced in bacteria. This study provides a detailed
      evaluation of the immune response to an important nematode antigen as a start to
      the unraveling of the complex interaction of these multicellular parasites with
      mammalian hosts.

PMID- 7622212
TI  - Level of receptor-associated protein moderates cellular susceptibility to
      pseudomonas exotoxin A.
AB  - Pseudomonas exotoxin A (PE) enters mammalian cells via a receptor-mediated
      endocytic pathway. The initial step in this pathway is binding to the multiligand
      receptor termed the alpha 2-macroglobulin receptor/low-density lipoprotein
      receptor-related protein (LRP). Binding of toxin, and of the many other ligands
      that bind to LRP, is blocked by the addition of a 39-kDa receptor-associated
      protein (RAP). Here we show that approximately 40% of the cell-associated LRP is
      on the surface of toxin-sensitive mouse LM fibroblasts and thus accessible for
      toxin internalization. The remainder is located intracellularly, primarily in the
      Golgi region. Mammalian cells exhibit a wide range of sensitivity to PE. To
      investigate possible reasons for this, we examined the expression levels of both
      LRP and RAP. Results from a variety of cell lines indicated that there was a
      positive correlation between LRP expression and toxin sensitivity. In the absence
      of LRP, cells were as much as 200-fold more resistant to PE compared with
      sensitive cells. A second group of resistant cells expressed LRP but had a high
      level of RAP. Thus, a toxin-resistant phenotype would be expected when cells
      expressed either low levels of LRP or high levels of LRP in the presence of high
      levels of RAP. We hypothesize that RAP has a pivotal role in moderating cellular
      susceptibility to PE.

PMID- 7622213
TI  - Downregulation by cryptococcal polysaccharide of tumor necrosis factor alpha and
      interleukin-1 beta secretion from human monocytes.
AB  - The regulation by Cryptococcus neoformans encapsulation of interleukin 1 beta (IL
      1 beta) and tumor necrosis factor alpha (TNF-alpha) production by human monocytes
      was investigated. By using encapsulated and acapsular C. neoformans, we
      demonstrated that both strains induce cytokine production, although the acapsular
      strain was a better stimulator than the thinly encapsulated strain. The cytokine
      levels produced by cells stimulated by the two strains were lower and followed a
      different kinetic than those stimulated by lipopolysaccharide (LPS). Purified
      capsular polysaccharide inhibits TNF-alpha secretion induced by LPS or acapsular
      C. neoformans. In contrast, no regulator effect on IL-1 beta was observed when
      LPS was used. The secretory response of these cytokines follows different
      pathways of macrophage activation; in fact, complete inhibition of TNF-alpha does
      not affect IL-1 beta production and vice versa. These data indicate that purified
      capsular polysaccharide of C. neoformans could contribute to the in vivo progress
      of cryptococcosis by suppressing cytokine production of macrophages and suggest
      that a therapeutic approach to address the suppressive effect of cryptococal
      polysaccharide could be devised.

PMID- 7622214
TI  - Construction and use of integration plasmids to generate site-specific mutations
      in the Actinomyces viscosus T14V chromosome.
AB  - Stable transformants of Actinomyces viscosus T14V carrying heterologous DNA were
      obtained with the aid of integration plasmids. These plasmids contained a
      kanamycin resistance (Kmr) gene flanked by A. viscosus T14V genomic DNA,
      including parts of the type 1 structural fimbrial subunit gene (fimP) on one or
      both sides of the antibiotic marker. Significantly more Kmr transformants were
      obtained with a plasmid carrying longer segments of homologous strain T14V DNA.
      Integration of this plasmid into the A. viscosus T14V genome affected the
      expression and function of type 1 fimbriae in the transformants. In the
      transformant strain designated A. viscosus MY50D, the inactivated fimP replaced
      the wild-type fimP via allelic replacement. A. viscosus MY51S and MY52S each
      contained a copy of the plasmid integrated into the genome by a Campbell-like
      insertion mechanism. A. viscosus MY50D and MY51S lacked type 1 fimbriae and did
      not bind to proline-rich proteins (the fimbrial receptors) immobilized on
      nitrocellulose. In contrast, strain MY52S synthesized the structural subunit
      protein, as detected by immunostaining with anti-A. viscosus T14V type 1 fimbria
      antibodies. However, the high-molecular-weight proteins observed in sodium
      dodecyl sulfate-polyacrylamide gels of fimbriae from the cell wall of the wild
      type strain T14V were absent in cell wall preparations of this strain. Moreover,
      A. viscosus MY52S failed to bind, in vitro, to proline-rich proteins. Thus, these
      results demonstrate that insertion of heterologous DNA at specific sites of the
      Actinomyces genome can be facilitated with integratable plasmids and that the
      transformants and mutants generated will aid in the delineation of the roles and
      contributions of specific genes to the structure and function of any
      macromolecule produced by these organisms.

PMID- 7622215
TI  - Enhanced respiratory clearance of nontypeable Haemophilus influenzae following
      mucosal immunization with P6 in a rat model.
AB  - Nontypeable Haemophilus influenzae (NTHi) is a common cause of infection of the
      respiratory tract in children and adults. The search for an effective vaccine
      against this pathogen has focused on components of the outer membrane, and
      peptidoglycan-associated lipoprotein P6 is among the proposed candidates. This
      study investigated the immunogenicity of P6 in a rat respiratory model. P6 was
      purified from two strains of NTHi, one capsule-deficient strain and an H.
      influenzae type b strain, and assessed for clearance of both homologous and
      heterologous bacterial strains following mucosal immunization. A protective
      immune response was determined by enhancement of pulmonary clearance of live
      bacteria and an increased rate of recruitment of phagocytic cells to the lungs.
      This was most effective when Peyer's patch immunization was accompanied by an
      intratracheal (IT) boost. However, the rate of bacterial clearance varied between
      strains, which suggests some differences in anti-P6 immunological defenses
      recognizing the expression of the highly conserved P6 lipoprotein on the
      bacterial surface in some strains. P6-specific antibodies in both serum and
      bronchoalveolar lavage fluid were cross-reactive and did not differ significantly
      in strain specificity, demonstrating that difference in clearance was unlikely
      due to differences in P6-specific antibody levels. Serum homologous and
      heterologous P6-antibody was bactericidal against NTHi even when enhanced
      clearance had not been observed. Peyer's patch immunization induced P6-specific
      CD4+ T-helper cell proliferation in lymphocytes isolated from the mesenteric
      lymph nodes. An IT boost increased the level of P6-specific antibodies in serum
      and bronchoalveolar lavage fluid, and P6-specific mesenteric node lymphocyte
      proliferation. Cells from rats immunized with P6 demonstrated proliferation
      following stimulation with P6 from nonhomologous strains; however, there was some
      variation in proliferative responses to P6 from different strains in lymphocytes
      isolated from animals immunized with killed bacteria. The increase in P6-specific
      antibodies and T-helper cell responses following an IT boost correlated with an
      increased rate of recruitment of phagocytic cells and enhanced bacterial
      clearance of both homologous and heterologous bacteria in the lungs. The data
      suggests that P6 has the potential to afford protection against pulmonary
      infection by NTHi following the induction of effective antigen-specific B- and T
      cell responses in mucosal tissues.

PMID- 7622217
TI  - Characterization of Pseudomonas aeruginosa fliO, a gene involved in flagellar
      biosynthesis and adherence.
AB  - Pseudomonas aeruginosa binds to eukaryotic cells via both pilus and nonpilus
      adhesins, while binding of P. aeruginosa to mucin is pilus independent. To
      characterize genes involved in non-pilus-mediated adherence, transposon mutants
      of the nonpiliated strain P. aeruginosa PAK-NP that are unable to bind to cells
      or mucins were isolated. Two such mutants, P. aeruginosa B164 and P. aeruginosa
      RR18, were identified previously as deficient in binding to eukaryotic cells or
      mucins as well as nonmotile. The transposon insertion in each of these strains
      was mapped to the same gene. Sequence analysis of both DNA flanking the
      transposons and plasmids that could complement the mutations indicated that this
      open reading frame encodes a putative protein homolog of both Escherichia coli
      FliO and Erwinia carotovora subsp. atroseptica MopB. The transposons in both of
      these mutants are nonpolar, since the addition of the P. aeruginosa fliO gene in
      trans restored adherence to both cells and mucins to these mutants. The cloned
      fliO gene also complemented the motility defect of both B164 and RR18. A 1.6-kb
      KpnI fragment from the PAK chromosome that contained the fliO gene was sequenced.
      The fliO gene appears to be part of an operon with a complete open reading frame
      upstream of the FliO homolog encoding a putative protein homolog of FliN of both
      E. coli and Salmonella typhimurium. The partial open reading frame downstream of
      fliO encodes a putative homolog of both E. coli and S. typhimurium FliP. The fliN
      gene is flanked on its 5'-end by the 3'-end of a homolog of a fliM gene. The P.
      aeruginosa FliN protein was identified with a T7 expression system, while all
      attempts to identify the P. aeruginosa FliO protein were unsuccessful. Homologs
      of P. aeruginosa FliO are involved in the biosynthesis of flagella, but the
      function of FliO in this biosynthetic process remains unknown. Further study
      should reveal the precise role of P. aeruginosa FliO in non-pilus-mediated
      adherence, which could include regulation of expression or localization of a
      nonpilus adhesin.

PMID- 7622219
TI  - A system for generalized mutagenesis of Haemophilus ducreyi.
AB  - The lack of a generalized mutagenesis system for Haemophilus ducreyi has hampered
      efforts to identify virulence factors expressed by this sexually transmitted
      pathogen. To address this issue, the transposable element Tn1545-delta 3, which
      encodes resistance to kanamycin, was evaluated for its ability to insert randomly
      into the H. ducreyi chromosome and produce stable, isogenic mutants.
      Electroporation of H. ducreyi with 1 microgram of plasmid pMS1 carrying Tn1545
      delta 3 resulted in the production of 10(4) kanamycin-resistant transformants;
      Southern blot analysis of a number of these transformants indicated that
      insertion of the transposon into the chromosome occurred at a number of different
      sites. This pMS1-based transposon delivery system was used to produce an H.
      ducreyi mutant that expressed an altered lipooligosaccharide (LOS). Passage of
      this mutant in vitro in the presence or absence of kanamycin did not affect the
      stability of the transposon insertion. To confirm that the observed mutant
      phenotype was the result of the transposon insertion, a chromosomal fragment
      containing Tn1545-delta 3 was cloned from this H. ducreyi LOS mutant.
      Electroporation of the wild-type H. ducreyi strain with this DNA fragment yielded
      numerous kanamycin-resistant transformants, the majority of which had the same
      altered LOS phenotype as the original mutant. Southern blot analysis confirmed
      the occurrence of proper allelic exchange in the LOS-deficient transformants
      obtained in this backcross experiment. The ability of Tn1545-delta 3 to produce
      insertion mutations in H. ducreyi should facilitate genetic analysis of this
      pathogen.

PMID- 7622216
TI  - Shigella infection induces cellular activation of T and B cells and distinct
      species-related changes in peripheral blood lymphocyte subsets during the course
      of the disease.
AB  - Immunophenotypic changes in peripheral blood lymphocytes (T, B, and NK cells) in
      patients during shigellosis was characterized by using triple-color flow
      cytometry. Eleven Shigella dysenteriae 1-infected adult patients (SDIP), 11
      Shigella flexneri-infected adult patients (SFIP), 15 age- and sex-matched healthy
      controls from Bangladesh (C-B), and 15 healthy volunteers from Sweden (V-S) were
      studied. In SDIP and SFIP, a significant increase in the CD45RO+ cells in both
      CD4+ and CD8+ T cells were seen. We found evidence for sequential T-cell
      activation, as shown by increased proportions of CD25 and CD4+ cells; HLA-DR and
      CD38 on CD8+ cells, and CD54 on CD4+ and CD8+ cells. We found differences in the
      lymphocyte activation and subset patterns related to the infecting Shigella
      species. Thus, a decrease in CD45 expression was seen in SFIP; this decrease
      progressed further during the disease. The proportions of NK cells (CD56+ cells)
      and CD3- CD8+ cells out of the total CD8+ cells were increased in SFIP but not in
      SDIP. The CD3+ CD8+ CD57+ T-cell subset was significantly lower in SDIP than in C
      B. The proportion of B-lymphocyte-expressing activation markers CD80 and CD23 was
      higher in patients than in C-B. There was a significant increase in the
      proportion of CD4+ T cells and a significant decrease in the percentages of total
      B cells, the CD3+ CD8+ CD57+ T-cell subset, and the CD56+ CD16+ NK-cell subset
      for V-S compared with C-B. Our results indicate that distinct subset changes and
      activation patterns are elicited in SDIP compared with SFIP and also that the
      degree of activation is related to disease severity. In addition, a common
      sequence of cell activation was seen during the disease course. The difference in
      the subset patterns seen in C-B and V-S may be related to differences in the
      levels or spectra of infectious agents in the environment.

PMID- 7622218
TI  - Characterization of lbpA, the structural gene for a lactoferrin receptor in
      Neisseria gonorrhoeae.
AB  - Neisseria gonorrhoeae acquires iron (Fe) efficiently from lactoferrin (LF). A 103
      kDa gonococcal outer membrane LF-binding protein (Lbp) was identified previously.
      We isolated the structural gene lbpA for Lbp1 by screening a gonococcal library
      for a clone that could repair an LF- receptor mutant. An mTnCm3 transposon
      insertion mutant of lbpA was unable to use LF-bound Fe for growth, unable to bind
      LF to whole cells, and unable to express Lbp1. The DNA sequence of lbpA predicted
      a protein that shared 94% identity with the meningococcal LF receptor protein,
      Lbp, and was closely related to Tbp1, one of the transferrin receptor proteins.
      Clinical isolates of gonococci are frequently unable to acquire Fe from LF, and
      LF- isolates do not have a functional LF receptor. The wild-type lbpA gene
      transformed most tested LF- clinical isolates to LF+, indicating that lbpA is
      defective in many clinical isolates.

PMID- 7622220
TI  - Cytokine-mediated activation of macrophages from Mycobacterium bovis BCG
      resistant and -susceptible mice: differential effects of corticosterone on
      antimycobacterial activity and expression of the Bcg gene (Candidate Nramp).
AB  - Previous work in our laboratory has shown that corticosterone increases the
      susceptibility of macrophages from Bcgs mice to the growth of Mycobacterium
      avium. The innate antimycobacterial activity of macrophages from Bcgr mice was
      not affected by corticosterone. In contrast to the differential effect of
      corticosterone on the antimycobacterial activity of the macrophages,
      corticosterone suppressed the production of tumor necrosis factor alpha and
      nitric oxide by macrophages from both Bcgr and Bcgs mice. The purpose of this
      investigation was to compare the effects of corticosterone on the
      antimycobacterial activity of macrophages from Bcgr and Bcgs mice that have been
      activated in vitro with recombinant gamma interferon or granulocyte-macrophage
      colony-stimulating factor. We found that macrophages from both strains of
      congenic mice responded equally to the activation stimuli. The capacity of the
      activated macrophages from Bcgs mice to suppress the growth of M. avium was
      inhibited by the addition of corticosterone to the cultures. The addition of NG
      monomethyl-L-arginine to the cultures did not affect the capacity of resident
      splenic macrophages from Bcgr mice to limit the growth of M. avium. However, NG
      monomethyl-L-arginine reduced the capacity of gamma interferon-activated, but not
      granulocyte-macrophage colony-stimulating factor-activated, macrophages to limit
      the growth of M. avium by macrophages from both Bcgr and Bcgs mice. The addition
      of corticosterone suppressed Nramp expression by macrophages from Bcgs mice.
      Nramp expression by macrophages from Bcgr mice was not affected by
      corticosterone.

PMID- 7622221
TI  - Functional capacities of clonal antibodies to Haemophilus influenzae type b
      polysaccharide.
AB  - Haemophilus influenzae type b (Hib) is an important pathogen for young children,
      and children can be protected with antibodies (Abs) to Hib polysaccharide (PS)
      capsule, a linear polymer of ribosyl ribitol phosphate. The structure of anti-Hib
      PS Abs has been well characterized at the molecular level; about two-thirds of
      anti-Hib-PS Abs use a V kappa gene named A2, and the remaining anti-Hib-PS Abs
      use one of many other VL genes. In order to understand the structural basis for
      the variability in the function of these Abs, we prepared 18 clonally pure Abs
      from adults and studied their affinity, avidity, bactericidal potency in vitro,
      and ability to reduce bacteremia in newborn rats. Affinities and avidities were
      determined as the inverse of the concentrations of short (3 repeating units) and
      long (20 repeating units) ligands which could bind 50% of anti-Hib-PS Ab in
      solution, respectively. No significant correlations between the protection of
      newborn rats and affinity (r = 0.02) or avidity (r = 0.16) were observed. The
      amount of Ab required to kill 50% of bacteria in vitro decreased with avidity (r
      = -0.32), as expected. However, Abs with high affinity were unexpectedly found to
      have less bactericidal activity (r = 0.38). This suggests that avidity may be a
      better predictor of Ab function than affinity. Affinity and avidity results were
      negatively correlated (r = 0.76, P = 0.0022), and Abs that had A2 V kappa gene
      products had higher avidity (P < 0.05) and lower affinity (P = 0.06) than Abs
      that had other VL genes. A possible explanation of these observations is that the
      epitope for Abs with the A2 gene is within the Hib-PS chain itself, whereas the
      epitope for Abs with a non-A2 gene is the terminus of Hib-PS.

PMID- 7622222
TI  - Expansion of gamma delta+ T cells in BALB/c mice infected with Leishmania major
      is dependent upon Th2-type CD4+ T cells.
AB  - T cells belong to either the alpha beta+ or gamma delta+ lineage as defined by
      their antigen receptor. Although both T-cell subsets have been shown to be
      involved in the immune response to the parasite Leishmania major, very little is
      known about possible interactions between these two populations. In this study,
      using a mouse model of infection with L. major, we showed that expansion of a
      subset of gamma delta+ T cells in vivo is dependent upon the presence of alpha
      beta+ CD4+ T cells. Moreover, this effect appears to be mediated via the
      secretion of lymphokines by CD4+ cells with a T-helper 2 (Th2) functional
      phenotype. Results showing that activation of Th2-type cells in mice treated with
      anti-immunoglobulin D antibodies or infected with Nippostrongylus brasiliensis
      also results in gamma delta+ T-cell expansion suggest that this effect of the Th2
      type CD4+ cells is a general phenomenon not restricted to infection with L.
      major.

PMID- 7622224
TI  - Analysis of a second bacteriophage hyaluronidase gene from Streptococcus
      pyogenes: evidence for a third hyaluronidase involved in extracellular enzymatic
      activity.
AB  - The hyaluronidase gene (hylP2) from a second group A streptococcal bacteriophage
      was isolated from ATCC T-type-22 hyaluronidase-producing strain 10403, a strain
      known to produce increased amounts of extracellular hyaluronidase. Sequence
      analysis of hylP2 and alignment with the previously described bacteriophage
      hyaluronidase gene (hylP) showed a high degree of similarity; however, hylP2 had
      deletions of regions specifying 34 amino acids. Twenty-eight of the deleted amino
      acids were in a region of HylP containing a series of collagen-like Gly-X-Y
      repeating units. By employing primers for both hylP and hylP2, PCR amplification
      resulted in fragments of appropriate sizes in 97% of the strains tested, with
      some strains producing two fragments, indicating the presence of at least two
      phages. When the hylP2 gene was introduced via a plasmid vector into a non
      hyaluronidase-producing Streptococcus pyogenes strain, this strain was still
      unable to produce extracellular hyaluronidase, although intracellular
      hyaluronidase was present. These results, along with the absence of a typical N
      terminal signal peptide, indicate that HylP2 is unable to be secreted into the
      extracellular milieu. Examination of more than 100 strains for production of
      hyaluronidase showed that only 23% of the strains produced extracellular
      hyaluronidase. One of these strains (strain 10403) contains a single
      bacteriophage hyaluronidase gene (hylP2) which, when inactivated by allelic
      replacement, still produces large amounts of extracellular hyaluronidase. These
      results suggest the presence of a different hyaluronidase gene encoding a protein
      that is actively secreted into the extracellular milieu.

PMID- 7622223
TI  - Analysis of human monoclonal antibodies elicited by vaccination with a
      Cryptococcus neoformans glucuronoxylomannan capsular polysaccharide vaccine.
AB  - The Cryptococcus neoformans capsular polysaccharide glucuronoxylomannan (GXM) has
      been conjugated to tetanus toxoid (GXM-TT) as an investigational vaccine. GXM-TT
      elicits antibodies that are protective in C. neoformans-infected mice. In an
      effort to characterize the fine specificity and molecular structure of human GXM
      TT-elicited antibodies, we generated two GXM monoclonal antibodies (MAbs) from
      peripheral blood lymphocytes of a volunteer GXM-TT recipient and studied serum
      GXM antibody idiotype expression in 10 additional vaccinees. The MAbs, 2E9 and
      3B6, are the immunoglobulin M(lambda) isotype and bind capsular polysaccharides
      of C. neoformans serotypes other than the serotype A that was used for
      immunization. Neither antibody competes with murine GXM MAbs for antigen binding,
      suggesting that the human MAbs recognize a different epitope. The B-cell
      superantigen staphylococcal protein A binds both MAbs, and human immunodeficiency
      virus gp120 binds 2E9. MAb nucleic acid sequence analysis revealed that both
      antibodies use an identical V lambda 1a-J lambda genetic element with different,
      somatically mutated, members of the VH3 gene family and different DH and JH gene
      elements. The gene elements used by both MAbs occur in fetal B-lymphocyte
      repertoires, autoantibodies, and other polysaccharide antibodies. Post-GXM-TT
      vaccination GXM antibodies from 10 additional vaccinees expressed a shared
      idiotype defined by rabbit antiserum raised against MAb 2E9. Our data suggest
      that the human GXM antibody response is restricted and raise questions regarding
      the importance of specific variable-region elements and superantigens in the
      generation of human antibody responses to encapsulated pathogens.

PMID- 7622225
TI  - Suppression of cytokines in mice by protein A-V antigen fusion peptide and
      restoration of synthesis by active immunization.
AB  - It is established that an approximately 70-kb Lcr plasmid enables Yersinia
      pestis, the causative agent of bubonic plague, to multiply in focal necrotic
      lesions within visceral organs of mice by preventing net synthesis of the
      cytokines tumor necrosis factor alpha (TNF-alpha) and gamma interferon (IFN
      gamma), thereby minimizing inflammation (Lcr+). Rabbit antiserum raised against
      cloned staphylococcal protein A-V antigen fusion peptide (PAV) is known to
      passively immunize mice against 10 minimum lethal doses of intravenously injected
      Lcr+ cells of Y. pestis. In this study, injected PAV suppressed TNF-alpha and IFN
      gamma in mice challenged with avirulent V antigen-deficient Y. pestis (lcrV or
      Lcr-) and promoted survival in vivo of these isolates as well as salmonellae and
      Listeria monocytogenes (with which the outcome was lethal). Active immunization
      of mice with PAV protected against 1,000 minimum lethal doses of intravenously
      injected Lcr+ cells of Y. pestis and Yersinia pseudotuberculosis but not Yersinia
      enterocolitica. The progressive necrosis provoked by Lcr+ cells of Y. pestis in
      visceral organs of nonimmunized mice was replaced after active immunization with
      PAV by massive infiltration of neutrophils and mononuclear cells (which generated
      protective granulomas indistinguishable from those formed against avirulent Lcr-
      mutants in nonimmunized mice). Distinct multiple abscesses typical of Lcr+ cells
      of Y. pseudotuberculosis were prevented by similar immunization. Significant
      synthesis of TNF-alpha and IFN-gamma occurred in spleens of mice actively
      immunized with PAV after challenge with Lcr+ cells of Y. pestis. These findings
      suggest that V antigen contributes to disease by suppressing the normal
      inflammatory response.

PMID- 7622226
TI  - Antibody response of the mouse reservoir of Borrelia burgdorferi in nature.
AB  - To determine whether the white-footed mouse reservoir host (Peromyscus leucopus)
      of the agent of Lyme disease (Borrelia burgdorferi) naturally mounts an immune
      response against the full range of antigens expressed by this zoonotic pathogen,
      we analyzed the pattern of immunoreactivity of these rodents at sites in which
      the intensity of transmission differs. Although the incidence of seroconversion
      within the reservoir population relates proportionally to the density of subadult
      deer ticks (Ixodes dammini), seroprevalence appears constant. About a fifth as
      many juvenile mice recognize spirachete antigens as do adult mice. Virtually all
      reservoir mice in nature recognize the p20, p35.5, p39, and p58 antigens,
      regardless of the intensity of transmission. Seropositive mice retain reactivity
      to a wide range of spirochetal antigens. Few mice recognize flagellin, OspB, and
      OspC. Although a third of serum samples include reactivity to a 31-kDa band, this
      reaction is irregular and may represent an uncharacterized antigen that
      comigrates with OspA. Mice captured where transmission is intense recognize the
      same spectrum of antigens as do mice captured where vector ticks are scarce.

PMID- 7622228
TI  - Exogenous myeloperoxidase enhances bacterial phagocytosis and intracellular
      killing by macrophages.
AB  - It is well documented that myeloperoxidase (MyPo) contributes to the bacterial
      activities of neutrophils and monocytes. Since mature macrophages (M phi) are
      devoid of this enzyme, its participation in M phi-mediated phagocytes and
      bacterial killing has not been completely defined. The present study demonstrates
      the exogenously added MyPo, at physiological levels, enhances both phagocytosis
      and killing of Escherichia coli. Murine peritoneal M phi were exposed to various
      concentrations of MyPo for different time intervals. Viable opsonized E. coli was
      added either prior to or after addition of MyPo. Thioglycolate-induced but not
      resident M pho exhibited an increase in the number of phagocytizing cells. Both
      resident and thioglycolate-induced M phi demonstrated increased bactericidal
      activity. Physiological levels of soluble MyPo also induced a significant
      increase in chemiluminescence. Since luminol-dependent chemiluminescence measures
      reactive oxygen intermediate production, studies were done to determine whether
      superoxide anion or H2O2 was involved in MyPo-induced M pho killing. Both
      superoxide dismutase and catalase ablated MyPo-induced bactericidal activity. The
      above data suggest that soluble MyPo, released from neutrophils at a site of
      infection or inflammation, can enhance both phagocytosis and killing of
      microorganisms.

PMID- 7622227
TI  - Cytokine modulation alters pulmonary clearance of Rhodococcus equi and
      development of granulomatous pneumonia.
AB  - Rhodococcus equi, a facultative intracellular bacterium, causes chronic, often
      fatal granulomatous pneumonia in young horses and in humans with AIDS. The
      inability of host alveolar macrophages to kill intracellular R. equi results in
      the development of granulomas and progressive loss of pulmonary parenchyma.
      Clearance of the organism from the lung requires functional CD4+ T cells. The
      purpose of this study was to identify the cytokine effector mechanisms that
      mediate clearance of R. equi from the lung. Mice were treated with monoclonal
      antibodies (MAbs) to either gamma interferon (IFN-gamma) or interleukin-4 (IL-4)
      to determine the role of endogenous production of these cytokines in pulmonary
      clearance of R. equi. Mice treated with an anti-IL-4 or isotype control MAb
      cleared R. equi by 21 days postinfection and expressed increased levels of IFN
      gamma mRNA, as detected by transcriptional analysis of bronchial lymph node CD4+
      T cells. In contrast, mice treated with the anti-IFN-gamma MAb failed to express
      detectable IFN-gamma mRNA, expressed increased levels of IL-4 mRNA, failed to
      clear pulmonary infection, and developed pulmonary granulomas with large numbers
      of eosinophils. The enhancement of IL-4 mRNA expression and a predominance of
      eosinophils in pulmonary lesions of anti-IFN-gamma-treated mice suggest that a
      nonprotective Th2 response in involved in disease pathogenesis. The association
      of increased bronchial lymph node CD4+ T-cell IFN-gamma mRNA expression with
      pulmonary clearance of R. equi suggests that a Th1 response is protective.

PMID- 7622229
TI  - Oral immunization of pigs with viable or inactivated Actinobacillus
      pleuropneumoniae serotype 9 induces pulmonary and systemic antibodies and
      protects against homologous aerosol challenge.
AB  - A dose-defined aerosol infection of pigs was used to study the immunogenic and
      protective potentials of oral immunization with dead or live Actinobacillus
      pleuropneumoniae serotype 9 reference strain CVI 13261 against an aerogenic
      challenge. Pigs were vaccinated with a single dose of 10(11) CFU of viable (n =
      8) or inactivated (n = 8) A. pleuropneumoniae given orally in a gelatin capsule.
      After 3 weeks, vaccinated pigs and nonvaccinated controls were challenged
      aerogenically with a dose of 10(8) CFU of A. pleuropneumoniae CVI 13261. The
      protective efficacy of oral immunization was evaluated by clinical and postmortem
      examinations. Bronchoalveolar lavage in pigs was performed during the experiment
      to obtain lavage samples for assessment of local antibodies. Isotype-specific
      antibody responses in sera and in bronchoalveolar lavage fluids were determined
      by enzyme-linked immunosorbent assays based on whole-cell antigen. Oral
      immunization did not induce clinical side effects. After aerosol challenge, two
      animals of both vaccinated groups (25% in each case) showed a moderate fever for
      2 days, whereas all four pigs (100%) of the nonvaccinated control group developed
      severe fever. In contrast to the controls, which developed severe
      pleuropneumonia, the vaccinated pigs had only mild pulmonary lesions. Three weeks
      after challenge, 13 of 16 vaccinated pigs (81%) were found to be free of
      pathomorphological changes of the lungs. From two of these pigs immunized with
      live bacteria we were able to reisolate A. pleuropneumoniae. A significant
      systemic and pulmonary increase in the concentrations of immunoglobulin A (IgA),
      IgM, and IgG antibodies reactive with A. pleuropneumoniae was detectable after
      aerosol challenge in both vaccinated groups. Immunization with viable bacteria
      was found to induce significantly higher concentrations of each Ig isotype in
      bronchoalveolar lavage fluids and sera than immunization with inactivated A.
      pleuropneumoniae. These serological findings were not reflected in the reduction
      in clinical disease after challenge in comparison to the case for the pigs
      vaccinated with inactivated bacteria. We concluded that a single oral
      administration of A. pleuropneumoniae provides partial clinical protection
      against aerosol challenge infection in the respiratory tract.

PMID- 7622230
TI  - The outer membranes of Brucella spp. are resistant to bactericidal cationic
      peptides.
AB  - The actions of polymyxin B, rabbit polymorphonuclear lysosome extracts, 14
      polycationic peptides (including defensin NP-2, cecropin P1, lactoferricin B, and
      active peptides from cationic protein 18 and bactenecin), EDTA, and Tris on
      Brucella spp. were studied, with other gram-negative bacteria as controls.
      Brucella spp. were comparatively resistant to all of the agents listed above and
      bound less polymyxin B, and their outer membranes (OMs) were neither
      morphologically altered nor permeabilized to lysozyme by polymyxin B
      concentrations, although both effects were observed for controls. EDTA and
      peptides increased or accelerated the partition of the hydrophobic probe N-phenyl
      naphthylamine into Escherichia coli and Haemophilus influenzae OMs but had no
      effect on Brucella OMs. Since Brucella and H. influenzae OMs are permeable to
      hydrophobic compounds (G. Martinez de Tejada and I. Moriyon, J. Bacteriol.
      175:5273-5275, 1993), the results show that such unusual permeability is not
      necessarily related to resistance to polycations. Although rough (R) B. abortus
      and B. ovis were more resistant than the controls were, there were qualitative
      and quantitative differences with smooth (S) brucellae; this may explain known
      host range and virulence differences. Brucella S-lipopolysaccharides (LPSs) had
      reduced affinities for polycations, and insertion of Brucella and Salmonella
      montevideo S-LPSs into the OM of a Brucella R-LPS mutant increased and decreased,
      respectively, its resistance to cationic peptides. The results show that the core
      lipid A of Brucella LPS plays a major role in polycation resistance and that O
      chain density also contributes significantly. It is proposed that the features
      described above contribute to Brucella resistance to the oxygen-independent
      systems of phagocytes.

PMID- 7622231
TI  - Increased translocation of Escherichia coli and development of arthritis in
      vitamin A-deficient rats.
AB  - We studied the immune response and the colonization pattern in vitamin A
      deficient rats that were colonized with the Escherichia coli O6 K13 pOmp 21
      strain, which is genetically manipulated to produce ovalbumin and to be resistant
      to ampicillin. In the vitamin A-deficient rats, the number of bacteria per gram
      of feces was about five times higher than in the paired fed control rats 4 weeks
      after colonization. In the control rats, the colon and the lower part of the
      ileum were colonized, while in the vitamin A-deficient rats all parts of the
      small intestine, as well as the colon, were heavily inhabited by bacteria.
      Furthermore, in 75% of the vitamin A-deficient rats, the E. coli bacteria were
      found in the mesenteric lymph nodes, and in 50% of the rats E. coli were found in
      the kidneys. These animals also developed severe arthritis. The levels of serum
      immunoglobulin G (IgG), IgM, IgE, and biliary IgA antibodies against the
      bacterial antigens were significantly higher in the vitamin A-deficient rats than
      in the control rats. The number of IgA-producing cells in the lamina propria of
      the small intestine was significantly lower in the vitamin A-deficient rats than
      in the control rats; however, there was an increase in the number of CD8+ cells
      and transforming growth factor beta-producing cells in the lamina propria of the
      vitamin A-deficient rats. Disturbances in T-cell function were demonstrated,
      since spleen cells from the vitamin A-deficient rats produced more gamma
      interferon and interleukin-2 in vitro than control spleen cells. In summary,
      vitamin A deficiency led to a decrease in the ability to control the localization
      of intestinal bacteria and an increase in translocation, which was followed by
      development of arthritis regardless of substantial levels of antibacterial
      antibodies. The bacterial invasion made the animals hyperresponsive to the
      bacterial antigens, despite the fact that vitamin A deficiency is normally
      associated with suppressed antibody production, as previously shown by us and
      others.

PMID- 7622232
TI  - pH and calcium dependence of hemolysis due to Rickettsia prowazekii: comparison
      with phospholipase activity.
AB  - Rickettsia prowazekii invades nucleated cells through phagocytosis and
      subsequently proliferates in the cytoplasm of the host cell. Hemolysis and a
      phospholipase A2 (PLA2) activity at neutral pHs have previously been reported;
      even though the phagosomal environment is most likely acidic. We here show that
      R. prowazekii and R. typhi also lyse erythrocytes at mildly acidic pHs,
      compatible with an early phagosomal compartment. For R. prowazekii, hemolysis at
      an acidic pH but not a neutral pH is enhanced by Ca2+, raising the possibility
      that more than one membranolytic factor may be produced by the rickettsiae. The
      rickettsiae alone display PLA2 activity, implying that the enzyme is of bacterial
      rather than erythrocyte or host cell origin. Moreover, the PLA2 activity requires
      divalent cations (Ca2+ or Mg2+), and, as with many extracellular PLA2s from other
      species, it has a preference for acidic over neutral phospholipids. The pH
      dependence of PLA2 is similar to that of the hemolysis without Ca2+, but in the
      presence of the hemolysis buffers (which contain Mg2+), there is no calcium
      induced enhancement at acidic pHs. Thus, these rickettsiae are endowed with a
      membranolytic activity that could contribute to the escape of the bacteria from
      early phagosomal compartments, and it is likely that multiple toxins may be used
      for membrane lysis.

PMID- 7622233
TI  - Purification and characterization of a Shiga toxin A subunit-CD4 fusion protein
      cytotoxic to human immunodeficiency virus-infected cells.
AB  - In a previous paper, we reported that a chimeric toxin composed of the enzymatic
      domain of the Shiga toxin A polypeptide (StxA1) genetically fused to the human
      CD4 (hCD4) molecule selectively kills cells infected with human immunodeficiency
      virus type 1 (HIV-1). Although other hCD4-containing chimeras cytotoxic to HIV
      infected cells have been developed, there is limited information regarding their
      receptor binding and internalization. Therefore, the goals of this study were to
      purify the StxA1-hCD4 fusion protein, identify the receptor(s), and investigate
      the cytosolic trafficking route used by the chimeric toxin. Sufficient quantities
      of the StxA1-hCD4 hybrid were isolated for this investigation by using the pET
      expression and purification system. Cos-1 cells were rendered sensitive to the
      StxA1-hCD4 chimera by transfection with the env gene, which encodes HIV-1
      envelope glycoproteins. The entry and translocation pathway used by the StxA1
      hCD4 hybrid toxin was investigated by assessing the protective capacities of
      chemical reagents which interfere with microfilament movement, acidification of
      endosomes, and the integrity of the Golgi apparatus. Our findings indicated that
      the chimera uses HIV-1 glycoprotein gp120, and perhaps gp41, as a receptor which
      directs its entry through receptor cycling. Uptake is pH independent, and the
      StxA1-hCD4 hybrid is apparently translocated to the Golgi complex as with other
      bipartite toxins.

PMID- 7622234
TI  - Down-regulation of gamma interferon, tumor necrosis factor type I, interleukin 1
      (IL-1) type I, IL-3, IL-4, and transforming growth factor beta type I receptors
      at the local site during the acute phase of Shigella infection.
AB  - An immunohistochemical technique was used to examine whether there was a
      colocalization of cytokine-specific receptors with cytokine-expressing cells. We
      have previously shown that there is extensive cytokine production and secretion
      in the rectal mucosa in shigellosis (interleukin 1 alpha [IL-1 alpha], IL-1 beta,
      IL-1ra, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor alpha [TNF-alpha], TNF
      beta, gamma interferon, granulocyte-macrophage colony-stimulating factor, and
      transforming growth factor beta [TGF-beta]) (R. Raqib, A. A. Lindberg, B.
      Wretlind, P. K. Bardhan, U. Andersson, and J. Andersson, Infect. Immun. 63:289
      296, 1995; R. Raqib, B. Wretlind, J. Andersson, and A. A. Lindberg, J. Infect.
      Dis. 171:376-384, 1995). Kinetics for receptor expression was compared with that
      for cytokine synthesis in the inflamed rectal mucosa from Shigella-infected
      patients during acute (2 to 6 days after onset of diarrhea) and convalescent (30
      to 40 days after onset) stages. Quantification of receptor expression was
      assessed by computer-assisted analysis of video microscopic images. A selective
      down-regulation of the receptors for gamma interferon, tumor necrosis factor (TNF
      receptor [TNFR] type I), IL-1 (IL-1 receptor [IL-1R] types I and type II), IL-3,
      IL-4, and TGF-beta (TGF-beta receptor type I) was observed at the onset of the
      disease, with a gradual reappearance during the convalescent stage. However, IL
      2R, IL-6R, granulocyte-macrophage colony-stimulating factor receptor, TNFR type
      II, and TGF-beta receptor type II showed no change in expression during the study
      period and were comparable to controls. Cytokine receptors were predominantly
      located to the epithelial layer of the mucosal surface and crypts, with variable
      expression patterns in the lamina propria. A time-dependent kinetic curve was
      seen for the soluble IL-2R (sIL-2R), sIL-6R, and sTNFR types I and type II shed
      in stool at the acute stage similar to that observed for cytokine secretion in
      stool but at four- to six-times-lower concentration. In contrast, soluble
      receptor levels in plasma were 100-fold higher than the cytokine levels. The
      results suggest a dissociation in immune regulation between cytokine production
      and cytokine receptor expression. The down-regulation of the receptors in acute
      shigellosis was probably a consequence of cytokine-induced internalization and
      shedding of the receptors during signal transduction as well as due to programmed
      regulatory roles played by cytokines and the bacterial antigens.

PMID- 7622235
TI  - Immunization of rats with synthetic peptide constructs from the glucan-binding or
      catalytic region of mutans streptococcal glucosyltransferase protects against
      dental caries.
AB  - Previously, we have described peptide constructs from two regions of
      glucosyltransferase (GTF) of mutans streptococci. A putative catalytic site in
      the amino-terminal half of the molecule and a repeated glucan-binding site in the
      carboxyl-terminal half of GTF were the regions upon which sequences were based.
      The present study explored the effects of immunization with these peptide
      constructs (called CAT or GLU) and with streptococcal GTFs from Streptococcus
      sobrinus and S. mutans on immunological, microbiological, and disease parameters.
      Groups of immunized Sprague-Dawley rats were infected with either 10(8) S.
      sobrinus 6715 or 10(8) S. mutans SJ32 organisms. Serum immunoglobulin G antibody
      levels, determined by enzyme-linked immunosorbent assay, to the respective
      peptide constructs and to the appropriate streptococcal GTF were significantly
      increased (after immunization) prior to infection and at the end of the
      experiment. Also, serum antibody from CAT-, GLU-, and S. sobrinus GTF-immunized
      rats inhibited S. sobrinus GTF-mediated insoluble glucan synthesis (all) and S.
      mutans GTF-mediated soluble glucan synthesis (all except anti-GLU) from sucrose.
      Immunization with the CAT or GLU peptide construct resulted in significantly
      reduced smooth surface and sulcal caries after infection with S. sobrinus. Sulcal
      dental caries after infection with S. mutans SJ32 were also significantly reduced
      in CAT- and GLU-immunized rats. Thus, immunization with peptides whose sequences
      are based on putative functional domains of mutans streptococcal GTF are
      protective toward a cariogenic S. sobrinus or S. mutans infection.

PMID- 7622236
TI  - Swine model of Haemophilus ducreyi infection.
AB  - Haemophilus ducreyi is a strict human pathogen that causes sexually transmitted
      genital ulcer disease. We infected domestic swine with H. ducreyi 35000,
      resulting in the development of cutaneous ulcers histologically resembling human
      chancroid lesions. Intraepidermal lesions progressed from pustules to ulcers
      containing polymorphonuclear leukocytes and were accompanied by a dermal
      inflammatory infiltrate containing T cells and macrophages. H. ducreyi was
      recovered from lesions up to 17 days after inoculation, and pigs did not develop
      immunity to reinfection with the challenge strain. Features of the model include
      inoculation through abrasions in the epidermis, ambient housing temperatures for
      infected pigs, the ability to deliver multiple different inocula to a single
      host, and the availability of monoclonal antibodies against porcine immune cells
      permitting immunohistochemical characterization of the host immune response to H.
      ducreyi infection.

PMID- 7622237
TI  - Role of Ca2+ in prostaglandin E2-induced T-lymphocyte proliferative suppression
      in sepsis.
AB  - Prostaglandin E2 (PGE2) has been known to modulate immune responses by inhibiting
      T-cell activation following hemorrhagic and traumatic injury. Recently, we
      documented a sepsis-related depression in concanavalin A (ConA)-induced T-cell
      proliferation and intracellular Ca2+ (Ca2+i) mobilization. The present study
      evaluated the potential role of PGE2 in the sepsis-related attenuation in Ca2+
      signaling and proliferation in T cells. Sepsis was induced in rats by implanting
      into their abdomen fecal pellets containing Escherichia coli (150 CFU) and
      Bacteroides fragilis (10(4) CFU). A group of rats implanted with septic pellets
      were treated with indomethacin at three consecutive time points. Levels of PGE2
      in blood were measured with a radioimmunoassay kit. ConA-induced [Ca2+]i
      mobilization in T cells obtained from indomethacin-treated and untreated rats was
      measured with Fura-2 and microfluorometry. We observed a 10-fold increase in PGE2
      levels in the circulation of septic rats compared with levels in rats implanted
      with bacterium-free sterilized pellets. The proliferative response and Ca2+i
      mobilization were significantly depressed in T cells obtained from septic rats 48
      h after implantations compared with those in rats implanted with sterile pellets.
      However, treatment of rats with the cyclooxygenase inhibitor indomethacin
      prevented the sepsis-related depression in ConA-induced T-cell Ca2+i mobilization
      as well as proliferation. Further, incubation of T cells from nonimplanted
      control rats with PGE2 resulted in a substantial depression in both T-cell
      proliferation and Ca2+i mobilization. The restoration of T-cell proliferation and
      Ca2+ signaling after indomethacin treatment of septic rats and the depression in
      the mitogen responsiveness in T cells previously exposed to PGE2 suggest that the
      PGE2 does play a significant role in the modulation of T-cell responses in septic
      rats and that such PGE2-induced suppression in T-cell activation is likely due to
      an attenuation in Ca2+ signaling.

PMID- 7622238
TI  - Identification of Babesia bovis merozoite antigens separated by continuous-flow
      electrophoresis that stimulate proliferation of helper T-cell clones derived from
      B. bovis-immune cattle.
AB  - To characterize Babesia bovis merozoite antigens that stimulate anamnestic T
      helper (Th)-cell responses from B. bovis-immune cattle, B. bovis-specific Th-cell
      lines and clones, previously assigned to different antigenic groups (W. C. Brown,
      S. Zhao, A. C. Rice-Ficht, K. S. Logan, and V. M. Woods, Infect. Immun. 60:4364
      4372, 1992), were tested in proliferation assays against fractionated merozoite
      antigens. The antigenic groups were determined by the patterns of response of Th
      clones to different parasite isolates and soluble or membrane forms of merozoite
      antigen. Soluble antigen fractionated by anion-exchange chromatography or gel
      filtration by using fast-performance liquid chromatography resolved two or three
      antigenic peaks, respectively. To enable fractionation of membrane-associated
      proteins and to resolve more precisely the proteins present in homogenized
      merozoites, a novel technique of continuous-flow electrophoresis was employed.
      Merozoite membranes or whole merozoites were homogenized and solubilized in
      sodium dodecyl sulfate-sample buffer, electrophoresed under reducing conditions
      on 15% or 10% acrylamide gels, eluted, and collected as fractions. Individual
      fractions were analyzed by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis and tested for the ability to stimulate Babesia-specific CD4+ T
      cell lines and clones. CD4+ Th-cell lines from two cattle displayed differential
      patterns of reactivity and detected numerous peaks of antigenic activity, ranging
      from < 14 to 76 kDa. Th-cell clones previously categorized into different
      antigenic groups detected antigenic peaks unique for clones representative of a
      given group. Antigens of 29, 51 to 52, and 85 to 95 kDa (group I), 40 kDa (group
      III), 20 kDa (group IV), 58 to 60 kDa (group VI), and 38, 45, and 83 kDa (group
      VII) were identified in the stimulatory fractions. Immunization of rabbits with
      selected fractions produced a panel of antisera that reacted specifically on
      Western blots (immunoblots) with merozoite antigens of similar sizes, leading to
      the tentative identification of candidate antigens of B. bovis merozoites with
      molecular masses of 20, 40, 44, 51 to 52 or 95, and 58 to 60 kDa that stimulate
      proliferation of Th clones representative of five different antigenic groups.
      These antisera may be useful for isolating recombinant proteins that are
      immunogenic for Th cells of immune cattle and therefore potentially useful for
      vaccine development.

PMID- 7622239
TI  - Yersinia pseudotuberculosis inhibits Fc receptor-mediated phagocytosis in J774
      cells.
AB  - Nonopsonized as well as immunoglobulin-G (IgG)-opsonized Yersinia
      pseudotuberculosis resists phagocytic uptake by the macrophage-like cell line
      J774 by a mechanism involving the plasmid-encoded proteins Yops. The tyrosine
      phosphatase YopH was of great importance for the antiphagocytic effect of the
      bacteria. YopH-negative mutants did not induce antiphagocytosis; instead, they
      were readily ingested, almost to the same extent as that of the translocation
      mutants YopB and YopD and the plasmid-cured strain. The bacterial determinant
      invasin was demonstrated to mediate phagocytosis of nonopsonized bacteria by
      these cells. In addition to inhibiting uptake of itself, Y. pseudotuberculosis
      also interfered with the phagocytic uptake of other types of prey: J774 cells
      that had been exposed to virulent Y. pseudotuberculosis exhibited a reduced
      capacity to ingest IgG-opsonized yeast particles. This effect was impaired when
      the bacterium-phagocyte interaction occurred in the presence of gentamicin,
      indicating a requirement for in situ bacterial protein synthesis. The Yersinia
      mediated antiphagocytic effect on J774 cells was reversible: after 18 h in the
      presence of gentamicin, the phagocytic capacity of Yersinia-exposed J774 cells
      was completely restored. Inhibition of the uptake of IgG-opsonized yeast
      particles was dependent on the Yops in a manner similar to that seen for blockage
      of Yersinia phagocytosis. This similarity suggests that the pathogen affected a
      general phagocytic mechanism. Despite a marked reduction in the capacity to
      ingest IgG-opsonized yeast particles, no effect was observed on the binding of
      the prey. Taken together, these results demonstrate that Yop-mediated
      antiphagocytosis by Y. pseudotuberculosis affects regulatory functions downstream
      of the phagocytic receptor and thereby extends to other types of phagocytosis.

PMID- 7622240
TI  - Cryptococcus neoformans melanin and virulence: mechanism of action.
AB  - Black melanin-like pigments are produced by several neurotropic fungi, including
      Cryptococcus neoformans. Pigment production is associated with virulence. In
      media containing phenolic substrates such as L-dopa, C. neoformans cells become
      black as a result of pigment accumulation. Pigmented and nonpigmented C.
      neoformans cells were studied with transmission electron microscopy and electron
      spin resonance (ESR) spectroscopy. Transmission electron microscopy showed
      electron-dense cell walls, and ESR spectroscopy revealed a stable free-radical
      population in pigmented cells. The ESR signals of pigmented cells were increased
      by light, alkaline pH, and Zn2+ and decreased by acid pH, indicating that the
      black pigment was a type of melanin. A mutant deficient in melanin synthesis
      (mel) generated by UV radiation lacked ESR-detectable radicals, was less virulent
      for mice, was more susceptible to killing by nitrogen- and oxygen-derived
      radicals, and had 100-foldless phenoloxidase activity than the parent strain. The
      interaction of melanized C. neoformans, nonmelanized C. neoformans, and the
      hypomelanotic mel mutant with J774.16 murine macrophage-like cells was studied.
      Melanized cells were more resistant to antibody-mediated phagocytosis and the
      antifungal effects of murine macrophages than nonmelanized cells. Small increases
      in the intensity of the ESR signals of melanized cells in solutions containing
      chemically generated oxygen- and nitrogen-derived radicals indicated electron
      transfer to or from melanin. Melanin appears to contribute to virulence by
      protecting fungal cells against attack by immune effector cells.

PMID- 7622241
TI  - A conserved Aeromonas salmonicida porin provides protective immunity to rainbow
      trout.
AB  - A protein with an apparent M(r) of 28,000 was isolated from outer membrane
      preparations of Aeromonas salmonicida A440. The protein was tested for the
      ability to form pores, using a planar lipid bilayer model membrane system. The
      protein appeared to be a monomer with a single-channel conductance in 1.0 M KCl
      of 1.96 nS and a cation/anion permeability ratio of 2.91 +/- 0.68. These data
      show that the porin channel is comparable in size to OmpC and OmpF of Escherichia
      coli and is relatively nonselective, having some preference for cations over
      anions. The porin was purified by preparative sodium dodecyl sulfate
      polyacrylamide gel electrophoresis, and a polyclonal antibody was raised.
      Immunoblot analysis showed that an immunologically cross-reactive protein was
      present in other Aeromonas strains but not in strains of Vibrio or Yersinia. The
      N-terminal amino acid sequence of the porin was determined and was found to show
      some homology to an Aeromonas hydrophila outer membrane protein. This is the
      second porin species of A. salmonicida to be described, and it differs from the
      other in subunit molecular weight, aggregation properties, peptidoglycan
      association, pore size, and antigenicity. Rainbow trout (Oncorhynchus mykiss)
      immunized intraperitoneally with the purified porin protein were significantly
      protected from experimental A. salmonicida challenge. This is the first report of
      successful vaccination against A. salmonicida with a purified outer membrane
      component.

PMID- 7622242
TI  - Quantitative comparison of clumping factor- and coagulase-mediated Staphylococcus
      aureus adhesion to surface-bound fibrinogen under flow.
AB  - The contributions of clumping factor and coagulase in mediating Staphylococcus
      aureus adhesion to surface-adsorbed fibrinogen have been quantified by using a
      new methodology and analysis. The attachment or detachment kinetics of bacteria
      were directly observed in a radial flow chamber with a well-defined laminar flow
      field and a spatially varying shear rate and were quantified by recursively
      scanning the chamber surface and counting cells via automated video microscopy
      and image analysis with a motorized stage and focus control. Intrinsic rate
      constants for attachment or detachment were estimated as functions of shear rate
      for the wild-type Newman strain of S. aureus and for mutants lacking clumping
      factor, coagulase, or both proteins on surfaces coated with plasma, fibrinogen,
      or albumin. Clumping factor, but not coagulase, increased the probability of
      attachment and decreased the probability of detachment of S. aureus on plasma
      coated surfaces; however, both clumping factor and, to a lesser extent, coagulase
      increased the probability of attachment on the purified-fibrinogen-coated
      surface. All mutants were resistant to detachment on the purified-fibrinogen
      coated surface, suggesting the possibility of an additional adhesion mechanism
      which was independent of coagulase or clumping factor and effective only for
      fully attached cells. Together, these results suggest that the presence of
      clumping factor plays the primary role in enhancing adhesion to surfaces with
      adsorbed fibrinogen, not only by enhancing the probability of cell attachment but
      also by increasing the strength of the resulting adhesion.

PMID- 7622243
TI  - Immunobiological activity of recombinant H antigen from Histoplasma capsulatum.
AB  - The H antigen from Histoplasma capsulatum is one of the known principal antigens
      of this fungus, but information regarding its identity and its participation in
      cellular immunity is largely unavailable. Therefore, we sought to determine both
      the nature of this antigen and the nature of its involvement in the cell-mediated
      immune response. The antigen was isolated from histoplasmin and digested with
      selected proteinases, and the cleavage products were subjected to reverse-phase
      high-performance liquid chromatography. Amino acid sequences of protein fragments
      were obtained by Edman degradation. A fragment of the gene encoding the H antigen
      was isolated by using degenerate primers in the PCR. This fragment was used to
      screen a genomic library, and the full-length gene was isolated and sequenced.
      The deduced amino acid sequence revealed homology to extracellular beta
      glucosidases. A cDNA was generated by reverse transcription PCR and cloned into
      the expression vector pET 19b. Recombinant H antigen was isolated from inclusion
      bodies of Escherichia coli and tested for its ability to elicit and induce an in
      vitro cell-mediated immune response in BALB/c mice. Recombinant antigen
      stimulated splenocytes from mice immunized with viable yeast cells or with
      antigen suspended in adjuvant. Mice inoculated with H antigen were not protected
      against either a sublethal or a lethal inoculum of yeast cells. Thus, H antigen
      stimulates a cell-mediated immune response but does not induce a protective
      response to H. capsulatum.

PMID- 7622244
TI  - Selective neutralization of a bacterial enterotoxin by serum immunoglobulin A in
      response to mucosal disease.
AB  - One-third of convalescent-phase serum samples (6 of 18) from patients with
      Clostridium difficle-associated diarrhea demonstrated neutralization of the
      clostridial enterotoxin, toxin A. Although appreciable amounts of toxin A
      specific immunoglobulin G (IgG) and IgA were present in these sera, the ability
      to neutralize the cytotoxic activity of toxin A on OTF9-63 cells in vitro was
      confined to the IgA fraction and the IgA1 subclass in serum samples from all six
      patients. In contrast to the patients with C. difficile diarrhea, this activity
      was present in both the IgA and IgG fractions in sera from two C. difficile
      infected patients without diarrhea, one of whom presented with a splenic abscess.
      Sera and purified IgA which neutralized the cytotoxicity of toxin A on OTF9-63
      cell cultures in vitro also neutralized the enterotoxicity of toxin A in rabbit
      ileal loops in vivo. This activity was not Fc dependent, since IgA retained
      neutralizing activity after pepsin digestion and F(ab')2 purification. The
      transition from nonneutralizing toxin A-specific IgA in the acute-phase sera to
      neutralizing specific IgA in the convalescent-phase sera was accompanied by a
      shift from a polymeric to a predominantly monomeric form of specific IgA.
      However, the neutralizing activity in convalescent-phase sera was present as both
      monomeric and polymeric IgA. Convalescent-phase sera from other patients with C.
      difficile diarrhea that failed to neutralize toxin A also failed to produce a
      predominantly monomeric-form specific IgA response. We conclude that serum IgA,
      not IgG, characteristically neutralizes toxin A in patients with C. difficile
      diarrhea who develop neutralizing systemic responses. This neutralization of an
      enteric bacterial toxin is a unique and selective role for serum IgA which
      provides a novel functional link between the systemic and mucosal immune systems.

PMID- 7622246
TI  - Functional domains of Pseudomonas aeruginosa exoenzyme S.
AB  - Recombinant exoenzyme S (rHisExoS) of Pseudomonas aeruginosa was expressed in
      Escherichia coli as a soluble, cytosolic His fusion protein. rHisExoS was
      purified by Ni(2+)-affinity chromatography in the presence of protease inhibitors
      without detectable degradation. rHisExoS possessed a specific activity (within
      twofold) for the factor-activating exoenzyme S-dependent ADP-ribosylation of
      soybean trypsin inhibitor (SBTI) similar to that of native exoenzyme S. Analysis
      of several deletion peptides showed that delta N222, which encoded the carboxyl
      terminal 222 amino acids of exoenzyme S, possessed factor-activating exoenzyme S
      dependent ADP-ribosyltransferase activity. delta N222 catalyzed the ADP
      ribosylation of SBTI at a rate sixfold greater than rHisExoS. Relative to
      rHisExoS, delta N222 had a similar affinity for NAD, a threefold greater affinity
      for SBTI, and a four- to eightfold greater kcat for the ADP-ribosylation of SBTI.
      Like native exoenzyme S, rHisExoS chromatographed as an aggregate with an
      apparent molecular mass of > 300 kDa. In contrast, delta N222 did not
      chromatograph as an aggregate, which showed that the amino-terminal 99 amino
      acids of exoenzyme S were responsible for the aggregation phenotype.

PMID- 7622245
TI  - The rare outer membrane protein, OmpL1, of pathogenic Leptospira species is a
      heat-modifiable porin.
AB  - The outer membranes of invasive spirochetes contain unusually small amounts of
      transmembrane proteins. Pathogenic Leptospira species produce a rare 31-kDa
      surface protein, OmpL1, which has a deduced amino acid sequence predictive of
      multiple transmembrane beta-strands. Studies were conducted to characterize the
      structure and function of this protein. Alkali, high-salt, and urea fractionation
      of leptospiral membranes demonstrated that OmpL1 is an integral membrane protein.
      The electrophoretic mobility of monomeric OmpL1 was modifiable by heat and
      reduction; complete denaturation of OmpL1 required prolonged boiling in sodium
      dodecyl sulfate (SDS), 8 M urea, and 2-mercaptoethanol. When solubilized in SDS
      at low temperature, a small proportion of OmpL1 exhibited an apparent molecular
      mass of approximately 90 kDa, indicating the existence of an SDS-unstable
      oligomer. OmpL1 dimers and trimers were demonstrated by nearest neighbor chemical
      cross-linking. In order to generate purified protein for functional studies, the
      ompL1 gene was ligated into the pMMB66 expression plasmid under control of the
      tac promoter. Although expression in Escherichia coli was toxic, most of the
      OmpL1 produced was found in the outer membrane, as determined by subcellular
      fractionation. Purified recombinant OmpL1 was reconstituted into planar lipid
      bilayers, demonstrating an average single channel conductance of 1.1 nS, similar
      to the major porin activity of native leptospiral membranes. These findings
      indicate that OmpL1 spans the leptospiral outer membrane and functions as a
      porin.

PMID- 7622247
TI  - Exogenous tumor necrosis factor alpha and interleukin-1 alpha increase resistance
      to Salmonella typhimurium: efficacy is influenced by the Ity and Lps loci.
AB  - Interleukin-1 alpha (IL-1 alpha) or tumor necrosis factor alpha (TNF-alpha)
      administered prior to infection with Salmonella typhimurium increases survival in
      mice that are Ityr, not in susceptible Lpsd or Itys mice. Combined IL-1 alpha and
      TNF-alpha pretreatment results in greater survival than that seen with either
      cytokine alone in Ityr mice. Treatment after infection with TNF-alpha and/or IL-1
      alpha increases the mean time to death but not the survival fraction of Lpsd mice
      and was ineffective in either Ityr or Itys mice.

PMID- 7622248
TI  - Comparison of spleen cell proliferation in response to Brucella abortus 2308
      lipopolysaccharide or proteins in mice vaccinated with strain 19 or RB51.
AB  - Mice vaccinated with Brucella abortus 19 (S19) or RB51 (SRB51) had spleen cells
      which proliferated in response to proteins of 32, 27, 18, and < 18 kDa but not in
      response to proteins of 106, 80, and 49 kDa from B. abortus 2308 (S2308)
      following vaccination and challenge infection with S2308. Spleen cells from mice
      vaccinated with S19 but not with SRB51 had increased proliferation in response to
      S2308 lipopolysaccharide (LPS) following challenge infection with S2308. We
      previously reported that mice vaccinated with S19 or SRB51, which were analyzed
      in the current study, have increased resistance to infection with S2308 and that
      only mice vaccinated with S19 produce antibody to S2308 LPS (M. Stevens, S.
      Olsen, G. Pugh, Jr., and D. Brees, Infect. Immun. 63:264-270, 1995). The results
      from our current and previous studies support the contention that vaccination of
      mice with S19 or SRB51 induces protection from infection with S2308 by cell
      mediated immune responses to the same immunodominant (32, 27, 18, and < 18 kDa)
      protein antigens of S2308. In addition, the absence of S2308 LPS-responsive
      spleen cells and antibody to S2308 LPS in mice vaccinated with SRB51 suggests
      that immune responses to LPS have no role in SRB51-induced protective immunity.

PMID- 7622249
TI  - Regulation of production of tumor necrosis factor alpha in monocytes stimulated
      by the 30-kilodalton antigen of Mycobacterium tuberculosis.
AB  - The 30-kDa secreted antigen of Mycobacterium tuberculosis was a strong inducer of
      tumor necrosis factor alpha in human monocytes. Our findings suggest that tumor
      necrosis factor alpha production may be up-regulated at both the
      posttranscriptional and transcriptional levels. Regulation at the
      posttranscriptional level probably reflects enhanced translational efficiency.

PMID- 7622250
TI  - Hemolytic activity of the Pasteurella haemolytica leukotoxin.
AB  - A Pasteurella haemolytica mutant incapable of producing leukotoxin was created by
      allelic replacement. Concentrated culture supernatants from wild-type P.
      haemolytica, but not from the mutant, contained the 102-kDa leukotoxin protein
      and lysed bovine lymphoma cells and sheep erythrocytes. Wild-type P. haemolytica
      demonstrated the typical beta-hemolytic phenotype on sheep and rabbit blood agar,
      whereas the mutant did not.

PMID- 7622253
TI  - Role of YadA-mediated collagen binding in arthritogenicity of Yersinia
      enterocolitica serotype O:8: experimental studies with rats.
AB  - Outer membrane protein YadA, Yersinia adhesin, is one of the plasmid-encoded
      virulence factors of yersiniae. YadA protects bacteria against host defense
      through several different mechanisms. One important role of YadA is to mediate
      binding to several collagen types. Our recent study revealed that a yadA null
      mutant of Yersinia enterocolitica serotype O:8 has a drastically reduced
      arthritogenic capacity when injected intravenously into Lewis rats. To further
      characterize the arthritogenic role of YadA, we repeated the rat experiments with
      strain Y. enterocolitica O:8/pYV082; this strain expresses a YadA deletion
      derivative lacking 22 amino acids from the amino-terminal hydrophobic region and
      does not bind to collagen. Y. enterocolitica O:8/pYV082 induced arthritis in 5 to
      14% of rats inoculated with arthritogenic doses, whereas the arthritis incidence
      with the wild-type parent strain was 65%. The parent strain was slightly more
      virulent than Y. enterocolitica O:8/pYV082, as determined by rat mortality. It
      also frequently induced skin abscesses, whereas Y. enterocolitica O:8/pYV082 did
      not. Infection kinetics in spleen and mesenteric lymph nodes were about the same
      with both of the bacterial strains used, and the same was true of the Yersinia
      specific antibody response. Altogether, these results suggest that YadA-mediated
      collagen binding contributes to the arthritogenicity of Y. enterocolitica O:8.

PMID- 7622251
TI  - Protection of C3H/He mice from experimental Borrelia burgdorferi infection by
      immunization with a 110-kilodalton fusion protein.
AB  - A 110-kDa Borrelia burgdorferi fusion protein, Escherichia coli expressing the
      fusion protein, transformed E. coli lacking the fusion protein insert, and
      lyophilized whole B. burgdorferi bacteria were compared for immunogenicity in
      C3H/He mice. Immunized mice were challenged with a variety of isolates from the
      United States or the European isolate P/Gau 3 weeks following the last
      inoculation. An average of 76.7% of the mice immunized with 25 micrograms of
      lyophilized whole B. burgdorferi cells were protected from infection, while 60%
      of the mice immunized with the 110-kDa fusion protein were protected. Whole E.
      coli bacteria expressing the fusion protein protected 57.7% of immunized mice
      against experimental challenge. Lower levels of protection occurred in mice
      challenged with the European isolate than in those challenged with isolates
      originating from the United States. These results demonstrate the potential of
      the 110-kDa fusion protein for use as a component of a subunit vaccine for
      prevention of Lyme borreliosis.

PMID- 7622252
TI  - Characterization of recombinant tetanus toxin derivatives suitable for vaccine
      development.
AB  - Recombinant derivatives of tetanus toxin (TeTx) were isolated and used to
      immunize mice. Recombinant TeTx light chain, a derivative of fragment C that had
      lost the ability to bind neurons, and a recombinant TeTx holotoxoid that could
      protect mice against TeTx challenge were identified.

PMID- 7622254
TI  - Localization of the promoter for the ptl genes of Bordetella pertussis, which
      encode proteins essential for secretion of pertussis toxin.
AB  - The ptl locus of Bordetella pertussis, which encodes proteins necessary for the
      secretion of pertussis toxin into the extracellular medium, is located directly
      downstream from the ptx locus, which encodes the structural subunits of the
      toxin. We have found that the ptx promoter is essential for expression of the ptl
      genes. A strain of B. pertussis which lacked only the ptx promotor region but
      which retained all other portions of the ptx-ptl region did not produce PtlF.
      Moreover, insertion of a functional ptx promoter from B. pertussis at the 5' end
      of the ptx region of Bordetella bronchiseptica resulted in the production of PtlF
      in B. bronchiseptica, a species which normally does not produce PtlF. These
      results suggest that the ptx operon is larger than originally proposed and
      contains both the ptx and ptl genes.

PMID- 7622255
TI  - T-cell cytokine responses in human infection with Mycobacterium tuberculosis.
AB  - Compared with healthy tuberculin reactors, Mycobacterium tuberculosis-stimulated
      peripheral blood mononuclear cells from tuberculosis patients had diminished
      production and mRNA expression of the Th1 cytokines gamma interferon and
      interleukin 2 (IL-2), with no change in production and mRNA expression for the
      Th2 cytokines IL-4, IL-10, and IL-13. These results were confirmed by evaluation
      of T cells and CD4+ cells. At the level of systemic T cells, development of
      tuberculosis is associated with diminished Th1 but not enhanced Th2 responses.

PMID- 7622256
TI  - S fimbriae of uropathogenic Escherichia coli bind to primary human renal proximal
      tubular epithelial cells but do not induce expression of intercellular adhesion
      molecule 1.
AB  - We have recently reported an increase of expression of the intercellular adhesion
      molecule 1 by renal carcinoma cells in response to S fimbriae of Escherichia
      coli. Now we demonstrate that E. coli expressing S and P fimbriae strongly binds
      to human proximal tubular epithelial cells. However, in primary and simian virus
      40-transfected renal tubular epithelial cells S fimbriae do not enhance the
      expression of intercellular adhesion molecule 1.

PMID- 7622257
TI  - Pefloxacin versus chloramphenicol in the therapy of typhoid fever.
AB  - An open, randomized clinical study was carried out to compare the clinical
      efficacy and safety of pefloxacin with that of chloramphenicol in the treatment
      of typhoid fever. Sixty hospitalized patients (40 men and 20 women, aged from 17
      to 64 years), affected by severe proven typhoid sepsis, were randomly assigned to
      treatment with pefloxacin at a daily dose of 1,200 mg for 15 days (Group A) or
      with chloramphenicol at a daily dose of 2 g for 15 days (Group B). The two groups
      of patients were statistically homogeneous regarding both age and sex and all
      patients were followed for 30 days after the end of therapy. In Group A all the
      patients completely recovered from infection and all the isolated strains of
      Salmonella typhi were eradicated by pefloxacin treatment. In Group B two patients
      had a relapse, two patients became chronic enteric carriers of S. typhi and only
      26 patients recovered from infection with complete eradication of the pathogen.
      The results indicate that pefloxacin is as active as chloramphenicol in the
      therapy of typhoid fever and that pefloxacin could be a valid antibacterial agent
      to be used together with appropriate hygienic measures for an eradication program
      of typhoid fever in the endemic countries.

PMID- 7622258
TI  - Dicloxacillin and flucloxacillin: pharmacokinetics, protein binding and serum
      bactericidal titers in healthy subjects after oral administration.
AB  - The pharmacokinetics of dicloxacillin and flucloxacillin were studied in 12
      healthy volunteers after oral administration. The participants received a single
      dose of either dicloxacillin (0.5 g, 0.75 g or 1.0 g) or flucloxacillin (0.75 g)
      in a cross-over fashion. Antibiotic concentrations were determined in serum and
      urine by bioassay and followed for 8 and 24 h, respectively. The three
      dicloxacillin dosages showed no significant differences for the serum elimination
      half-lives (t1/2 beta, median: 72 min). Comparing 0.75 g flucloxacillin with the
      same dose of dicloxacillin, no significant differences between the values of
      Cmax, t1/2 beta and AUC were found. Protein binding as determined by
      ultrafiltration in pooled serum was 94.7-96.2% for flucloxacillin and 96.4-97.2%
      for dicloxacillin. The serum bactericidal titers were similar for the two drugs.
      In conclusion, dicloxacillin and flucloxacillin showed similar pharmacokinetic
      behavior after 0.75 g doses in human volunteers.

PMID- 7622259
TI  - Five days of antibacterial therapy for bacterial meningitis in children?
AB  - We evaluated the effectiveness of 5-day antibacterial therapy for bacterial
      meningitis in children. The study group included 26 children from 2 months to 15
      years of age, admitted with microbiologically confirmed bacterial meningitis in
      1990-1993 and treated for 5 days. A historical comparison group of 49 patients
      treated for 8 to 15 days was used. Penicillin monotherapy (300 mg/kg body weight)
      was used for meningococcal and pneumococcal meningitis and ampicillin (300 mg/kg
      body weight) for Haemophilus influenzae b meningitis. On day 5 of therapy the
      activity of aspartate aminotransferase (AST), lactic dehydrogenase (LDH),
      creatine phosphokinase (CPK) and gamma-glutamyl-transpeptidase (gamma GT) in the
      CSF was determined by photocolorimetric assay and the concentration of creatine
      kinase BB (CK-BB) by ELISA. IL-6 was analysed using EIA technique and a cerebral
      ultrasound was performed at the time of the termination of the antibacterial
      therapy. The mean follow-up time was 1.3 years for children in the study group
      and 3.2 in the control group. The time of hospitalisation was shorter in children
      treated for 5 days (p < 0.005). Complete clinical recovery was 81% in the study
      group and 66% in the comparison group at the time of the termination of
      antibacterial therapy. No relapses occurred. The activity of AST, CPK, LDH, and
      gamma GT in the CSF had returned to normal by the 5th day of therapy, but almost
      a 7-fold higher concentration of CK-BB was registered. The concentration of IL-6
      in the CSF decreased with the therapy from 1,800 pg/ml to 685 pg/ml but still
      remained high.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7622260
TI  - Rhabdomyolysis complicating acute Epstein-Barr virus infection.
AB  - Infection with Epstein-Barr virus (EBV) is common and induces a broad spectrum of
      illness. In the majority of cases the disease manifests with typical signs of
      heterophile-positive infectious mononucleosis in which myalgia may be seen in up
      to 20% of cases. In this study, a case of rhabdomyolysis is reported occurring
      during the clinical course of an 18-year-old patient with infectious
      mononucleosis. This severe form of muscle involvement has been rarely associated
      with EBV infections. Five similar cases previously published in the English
      literature are also reviewed. The clinical implications of rhabdomyolysis and
      infectious mononucleosis are discussed.

PMID- 7622263
TI  - Nocardia asteroides buttock abscess.

PMID- 7622262
TI  - An unusual amebic localization on the right hip.
AB  - We report the history of a 43-year-old man with a histopathologically confirmed
      invasive amebic abscess in his right hip. CT scan of the liver was normal. The
      amebic indirect hemagglutination (IHA) test was positive with a titer of 1/1,024.
      The patient developed acute renal failure and died within 48 h of admission with
      multiple organ failure due to sepsis.

PMID- 7622261
TI  - Arthritis due to a penicillinase-producing Neisseria gonorrhoeae from Saudi
      Arabia.
AB  - A case of arthritis due to a penicillinase-producing Neisseria gonorrhoeae in a
      29-year-old lady is reported. The organism was isolated from the synovial fluid
      of the affected joint. Isolation of penicillinase-producing N. gonorrhoeae from
      such fluid has only rarely been reported. However, this is probably the first
      reported case from the Middle East and surrounding areas.

PMID- 7622264
TI  - Septicaemia, meningitis and spondylodiscitis caused by Streptococcus suis type 2.

PMID- 7622265
TI  - Diagnosing bacterial infectious diseases in one hour: an essential upcoming
      revolution.

PMID- 7622266
TI  - Infections due to Actinomyces neuii (former "CDC coryneform group 1" bacteria).
AB  - Sixty-seven patients with infections in which the recently proposed species
      Actinomyces neuii was involved were observed during a 4 1/2-year period.
      Microbiological as well as clinical features of the patients are presented. A.
      neuii does not cause typical actinomycosis and is detected most often in material
      from abscesses or infected atheromas. One case of a fatal septicemia caused by A.
      neuii in a non-immunocompromised host was seen. Antimicrobial susceptibility
      patterns of A. neuii isolates and results of various treatment regimens are
      discussed.

PMID- 7622267
TI  - Epidemiology and attack index of gram-negative bacteria causing invasive
      infection in three special-care neonatal units and risk factors for infection.
AB  - Of 13 consecutive episodes of gram-negative septicemia (Escherichia coli eight,
      Klebsiella oxytoca four, Klebsiella pneumoniae one) among 113 infants in three
      special-care neonatal units studied, five episodes were epidemiologically related
      according to a novel fingerprinting method for enterobacteria. In ten episodes
      the invasive phenotype was found in the fecal flora of up to 54% of the fellow
      infants in the same ward and for periods of up to 70 days. Two units exchanged
      patients, which further promoted the transmission of invasive strains. The attack
      index was highest for certain E. coli strains, generally low for K. oxytoca
      strains, but lowest for other E. coli strains. The infants contracting septicemia
      had lower birth weight (p = 0.04) or were more often classified as high-risk
      infants than matched non-infected fecal carriers of the invasive strains (p =
      0.04). In summary, gram-negative neonatal septicemia was either due to an
      apparently high-virulent strain capable of attacking the single full-term infant
      carrier or a high-colonizing phenotype of lower apparent virulence, which
      occasionally attacked a high-risk infant among a large number of infants
      colonized.

PMID- 7622268
TI  - Vaginal microbiological flora and sexually transmitted diseases in women with
      recurrent or current vulvovaginal candidiasis.
AB  - A history of recurrent vulvovaginal candidiasis (RVVC) was reported by 102 women,
      while current vulvovaginal candidiasis (VVC) was diagnosed in 83 of the same 996
      women. They had all attended two family planning and one youth clinic,
      respectively. Two women, without RVVC or VVC, matched for age for each case of
      RVVC, were selected as a comparison group (COMP). Recurrent, but not current VVC,
      was associated with a history of sexually transmitted disease. Those with
      current, but not with recurrent, VVC had significantly more often genital warts
      and bacteriuria (> 10(5) bacteria/ml), but significantly less often bacterial
      vaginosis than the COMP women. Both VVC and RVVC were inversely correlated to a
      vaginal flora change with a mixed anaerobic vaginal flora. Those with VVC had a
      greater number of lactobacilli on vaginal cultures, than those with RVVC and the
      women in the COMP group. VVC and a history of RVVC both occurred more frequently
      in women with a lactobacilli-predominated vaginal flora, as compared with those
      with a flora change with a mixture of anaerobic and facultative anaerobic
      bacteria.

PMID- 7622269
TI  - Epidemiology of alveolar echinococcosis in southern Germany (Bavaria).
AB  - Alveolar echinococcosis is considered to be the most dangerous endemic parasitic
      disease for man in Central Europe. In Germany, unlike the neighbouring countries
      of Switzerland, Austria and France, only limited data on the prevalence and
      incidence of echinococcosis are available. Therefore, a retrospective cross
      sectional study was conducted in order to investigate the epidemiology of
      echinococcosis in Bavaria, one of the two southern states of Germany. A
      standardised questionnaire was sent to all hospitals in Bavaria requesting
      information about patients seen from 1985 to 1989. In a second step a team of
      reviewers was sent to all relevant hospitals for active case finding in hospital
      statistics and medical records. A total of 216 patients with echinococcosis were
      detected of whom 58 had alveolar echinococcosis. According to these data, the
      prevalence in Bavaria was calculated to be 0.5 per 100,000 inhabitants with peak
      values in the counties of Swabia (2.4) and Upper Bavaria (0.6). The annual mean
      incidence of newly diagnosed cases amounted to 0.03 per 100,000. The distribution
      of prevalence in man was closely correlated to the infection rates in foxes
      throughout Bavaria (p < 0.05). Farmers are the occupational group with the
      highest risk to acquire echinococcosis with a prevalence/odds ratio of 14.6 for
      Swabia and 8.8 for Upper Bavaria, when compared to the general rural population.

PMID- 7622270
TI  - The influence of the regular use of a soap or an acidic syndet bar on pre-acne.
AB  - The role of regular skin cleansing with soap or syndet in pre-acne is ill
      defined. The intention of this study was to assess the relative value of an
      acidic syndet bar and a conventional soap bar in the prevention of acne lesions
      in acne-prone patients. In a randomized, open, comparative trial the three
      months' application of either an acidic syndet bar or a conventional soap to
      facial skin for 1 min each in the morning and in the evening was compared in 120
      adolescents and young adults with inflammatory acne grade I or II according to
      the Plewig and Kligman classification. It was a confirmatory trial with the
      number of inflammatory lesions being the prime parameter of concern. In addition,
      non-inflammatory acne lesions were analyzed as were parameters of safety such as
      itching, redness and scaling. While the number of inflammatory acne lesions,
      i.e., papulopustules, did not differ in the two trial groups composed of 57
      evaluable cases each, this was the case from 4 weeks of application onward: in
      the group using soap the mean number of inflammatory lesions increased from 14.6
      (+/- 5.3) to 15.3 (+/- 6.0), while it decreased in the other group from 13.4 (+/-
      5.2) to 10.4 (+/- 5.8) (p < 0.0001). Symptoms or signs of irritation were seen in
      40.4% of individuals belonging to the former and 1.8% belonging to the latter
      group. The number of papulopustules characteristic of inflammatory acne thus is
      clearly lower when a syndet bar of the acidic type is regularly used for
      cleansing the face as compared to a (necessarily alkaline) soap.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7622271
TI  - Imported rickettsioses in German travelers.
AB  - Twenty-two cases of rickettsiosis imported to Germany (13 men, nine women,
      average age 42 years) in a 5-year period were analyzed retrospectively regarding
      the travel histories, symptoms and clinical findings, laboratory features and
      course of the disease. The two primary rickettsial diseases were boutonneuse
      fever (18 patients) and scrub typhus (three patients). One patient had murine
      typhus. The main symptom was fever in 91% followed by headache (64%), myalgia
      (40%), arthralgia (50%) and diarrhea (36%). The most frequent clinical finding
      was lymphadenopathy in 65%. Eschar was detectable in 55% of patients with
      Rickettsia conori infection and in one patient with Rickettsia tsutsugamushi
      infection. All patients with R. tsutsugamushi infection as well as 33% of the
      patients with R. conori infection had a macular exanthema. One patient with scrub
      typhus had pleural and pericardial effusions. Seventy-three percent had an
      increased ESR. Three patients had leucocytosis, three increased transaminases and
      two normochromic anemia. The incubation period for R. conori infection was 5 to
      28 days (average 14 days), for R. tsutsugamushi infection 7 to 21 days (average
      16 days). Twenty-one patients were treated with tetracycline or doxycycline, one
      with erythromycin. All patients were cured. One patient had a relapse. Due to the
      fact that the symptoms are often not characteristic and that the routine
      laboratory findings are of only marginal help, the diagnosis of rickettsial
      diseases is often not easy. A detailed travel history sometimes gives an
      important hint for diagnosis.

PMID- 7622273
TI  - Occupational medicine as a science in Germany and the European Union.

PMID- 7622272
TI  - A comparative trial of low dose cefaclor and macrocrystalline nitrofurantoin in
      the prevention of recurrent urinary tract infection.
AB  - One hundred and twenty women, aged between 18 and 90 years, with a history of at
      least four episodes of symptomatic urinary tract infection in the preceding 12
      months, were randomized in an open, prospective study to prophylactic treatment
      with cefaclor 250 mg at bedtime or macrocrystalline nitrofurantoin 50 mg at
      bedtime for 12 months. Ninety-seven (49 taking cefaclor, 48 taking
      macrocrystalline nitrofurantoin) were assessed for efficacy; 80% of these were
      symptomatically improved and remained abacteriuric during the period of
      prophylaxis. Symptomatic attacks while patients were taking prophylaxis occurred
      at least five times less often than before prophylaxis had started. Seventy
      percent of the patients continued in an improved condition after having stopped
      prophylaxis. All 120 patients were assessed for adverse events; these were twice
      as frequent in patients taking macrocrystalline nitrofurantoin (20% vs. 10%), but
      only 11 patients (three taking cefaclor, eight taking macrocrystalline
      nitrofurantoin) withdrew from the study. Due to the small numbers of patients
      experiencing adverse events, these differences are not statistically significant.
      No significant changes in haematological or biochemical parameters were found
      during or after the end of the 12-month course. The 22 patients assessable for
      efficacy who had a non-obstructive radiological abnormality responded as well to
      prophylaxis as those with no detectable abnormality. Long-term, low-dose
      prophylaxis with a suitable antimicrobial agent is highly effective management
      for patients with recurrent urinary tract infections, and can appropriately be
      provided by the family doctor. Prophylaxis given for 1 year gives better results
      than when given for 6 months.

PMID- 7622274
TI  - A case-control study of trapezius muscle activity in office and manual workers
      with shoulder and neck pain and symptom-free controls.
AB  - A case-control study with matched pairs was initiated to investigate the
      relationship between shoulder-neck complaints and activity in the upper trapezius
      muscle. The matching was done so that the physical demands from work (external
      exposure) were equal for both the case and the control. Each pair was also
      matched for gender, age, working hours, and employment time. Male (n = 18) and
      female workers (n = 78) employed in both manual and office work were included.
      Muscle activation levels and pause patterns during work and muscle activity
      during tests of attention, coordination, and rest were recorded by surface
      electromyography. The results showed consistent associations between pain and
      signs of increased activation of the trapezius for the cases in the manual group.
      No such associations were observed in the office group. The results are
      consistent with the hypothesis that muscle activation patterns may in some
      instances, but not in all, explain why some workers develop pain while others do
      not in work situations where the physical demands are similar.

PMID- 7622275
TI  - Urinary methylchloroform rather than urinary metabolites as an indicator of
      occupational exposure to methylchloroform.
AB  - In order to compare methylchloroform (MC, or 1,1,1-trichloroethane) per se and
      its metabolites in urine as indicators of occupational exposure to this solvent,
      50 male solvent workers were studied in the second half of a working week to
      evaluate the exposure-excretion relationship. The time-weighted average intensity
      of solvent exposure of individuals during an 8-h shift was monitored by personal
      diffusive sampling. Urine samples were collected near the end of the shift and
      were analyzed for MC and its metabolites [i.e., trichloroacetic acid (TCA),
      trichloroethanol (TCE) and total trichloro-compounds (TTC; the sum of TCA and
      TCE)] by head-space gas chromatography. MC per se, TCA, TCE, and TTC in urine
      correlated significantly (P < 0.01) with MC in ambient air, and among the four
      the correlation coefficient was highest for MC. The same result were obtained by
      multiple regression analysis in which ambient air MC was taken as the dependent
      variable and either the three indicators urinary MC, TCA, and TCE or the two
      indicators urinary MC and TTC were taken as independent variables. Taking the
      specificity and selectivity of the analyte as well as the simple and hazardous
      chemical-free procedure of analysis into consideration, it is concluded that MC
      is the analyte of choice as an indicator of occupational exposure to MC, when
      urine is selected as a specimen available by noninvasive sampling.

PMID- 7622276
TI  - Retention of styrene following controlled exposure to constant and fluctuating
      air concentrations.
AB  - An experiment was designed to determine whether the respiratory retention of
      styrene vapor, as estimated from measurements of end-exhaled air, was the same
      during periods of both constant and fluctuating exposure. Six human subjects were
      exposed to styrene inside a experimental chamber. A computer-controlled system
      was used to generate time-varying air concentrations of styrene over 4-5h in both
      multistep sequences of constant exposure (four subjects exposed to 15-99 ppm of
      styrene in 100-min steps) and fluctuating patterns representative of occupational
      exposures (two subjects exposed to mean concentrations of styrene of 50 ppm). In
      the latter case, lognormally distributed exposures, which fit one of two first
      order autoregressive models, were generated at intervals of 2.5 min. It was found
      that the concentration of styrene in end-exhaled air was reduced by about half if
      the subject inhaled one to three breaths of clean air prior to sampling. This
      suggests that significant amounts of styrene were desorbed from the lining of the
      lungs during the initial exhalation. The retention of styrene vapor during
      constant exposures was 0.935 and was independent of the level. During each of the
      two sets of fluctuating exposure the retention of styrene was also constant and
      was independent of both the variance and autocorrelation coefficient. However,
      the retention of styrene during the fluctuating exposure (estimates ranged from
      0.957 to 0.973) was significantly higher than that observed during the constant
      exposures.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7622277
TI  - DNA single strand break analysis in mononuclear blood cells of petrol pump
      attendants.
AB  - DNA single strand breaks, including DNA adducts that lead to alkali-labile sites,
      were measured in peripheral mononuclear blood cells of 35 petrol pump attendants
      by alkaline filter elution. Blood samples from petrol pump attendants were taken
      on Monday and Friday. Additionally, DNA single strand breaks of smoking and non
      smoking control persons were examined. For the smoking (n = 12) and the non
      smoking controls (n = 20) a mean normalized elution rate of 1.49 +/- 0.52 (mean
      value +/- 95% confidence interval) and 1.32 +/- 0.28, respectively, was obtained.
      The difference between smoking and non-smoking controls was not statistically
      significant (U test). An increase in DNA single strand breaks from Monday to
      Friday was detected for non-smoking petrol pump attendants with a daily working
      time of more than 4 h at the pump station. Their mean normalized elution rate
      increased from 1.08 on Monday to 1.89 on Friday. This difference was
      statistically significant (P < 0.05; Wilcoxon test for paired data), although the
      95% confidence interval was large on Friday (0.43 on Monday; 1.23 on Friday).
      However, no significant increase was found for non-smoking petrol pump attendants
      who were on duty for less than 4 h per day at the pump station. No statistically
      significant increase in DNA single strand breaks could be detected for smoking
      petrol pump attendants whether they were pumping gasoline for more or for less
      than 4 h per day.

PMID- 7622278
TI  - Biological monitoring of workers exposed to N, N-dimethylfomamide. I. Methods of
      analysis.
AB  - Some methods for analysing N,N-dimethylformamide and its metabolites
      [hydroxymethyl-N-methylformamide, hydroxymethylformamide and N-acetyl-S-(N
      methylcarbamoyl)cysteine] in the urine of exposed workers are described.
      Unchanged dimethylformamide was measured after pretreatment of urine (2 ml) with
      silica gel cartridges and elution with methanol. The gas chromatographic analysis
      using a nitrogen phosphor detector made it possible to detect N,N
      dimethylformamide in urine even when workers were exposed to low concentrations
      of the solvent (about 1 mg/m3). N-Hydroxymethyl-N-methylformamide and N
      hydroxymethylformamide were analysed as N-methylformamide and formamide
      respectively after direct injection of urine into the gas chromatograph. The
      injection port temperature played an important role in the gas chromatographic
      determination of these products. Reliable results were obtained when direct or
      split injections were performed at 250 degrees C. The splitless injection gave
      the same reliable results at 150 degrees C. In urine samples from occupationally
      non-exposed persons, N-methylformamide could not be detected. In contrast,
      formamide (or its precursor, hydroxymethylformamide) was present in every urine
      sample. Our results in respect of 19 urine samples analysed with the injection
      port of the gas chromatograph at 250 degrees C gave a mean of 8.6 mg/l of
      formamide. N-Acetyl-S-(N-methylcarbamoyl)cysteine was determined using a modified
      method for analysing organic acid in urine samples. The metabolite was extracted
      with ethyl ether in an acid environment, treated with a silylating reagent and
      measured by gas chromatography/mass spectrometry.

PMID- 7622279
TI  - Biological monitoring of workers exposed to N-N-dimethylformamide. II.
      Dimethylformamide and its metabolites in urine of exposed workers.
AB  - N,N-Dimethylformamide (DMF) exposure was monitored in a synthetic leather
      factory; at the same time, urinary dimethylformamide and its metabolites were
      measured in urine samples collected before and at the end of workshifts. The
      study was run during two different periods. During the first phase ten workers
      were observed for 3 days (Monday, Tuesday and Wednesday) in the same week. In the
      second phase 16 workers were involved in the study on a Friday and on the
      following Monday. Urinary DMF, as well as hydroxymethyl-N-methylformamide and
      hydroxymethylformamide [measured as N-methylformamide (NMF) and formamide,
      respectively], were measured as a "physiological" product in subjects not exposed
      to dimethylformamide. Environmental exposure to DMF ranged between 10 and 25
      mg/m3. The unmodified solvent found in urine collected at the end of the exposure
      was significantly related to the environmental concentrations of DMF; its urinary
      concentrations were found to range between 0.1 and 1 mg/l. Higher concentrations
      of NMF (mean 23.3 mg/l) and formamide (24.7 mg/l) were measured in urine samples
      collected at the end of workshifts. The same concentrations were related to
      individual exposures to DMF. N-Acetyl-S-(N-methylcarbamoyl)cysteine in the urine
      of workers exposed to DMF showed a mean concentration of 40.4 mg/l on Friday
      (before and after the workshift) and a mean concentration of 10.3 mg/l on Monday.
      Its slow kinetic profile favours its body accumulation during the working
      week.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7622280
TI  - Carbon disulphide. II. Investigations on the uptake of CS2 and the excretion of
      its metabolite 2-thiothiazolidine-4-carboxylic acid after occupational exposure.
AB  - The reported investigations on the uptake of carbon disulphide (CS2) and the
      excretion of its metabolite 2-thiothiazolidine-4-carboxylic acid (TTCA) were
      based on results from 403 personal air samples (352 passive and 51 active
      samples) and 362 TTCA determinations in biological material measured during a
      field study on the adverse effects due to CS2 exposure. The external exposure
      ranged from below the detection limit (0.2 ppm) to 66 ppm and the urinary TTCA
      excretion from below the detection limit (0.16 mg./l) to 33.4 mg/l. The excretion
      of TTCA in postshift urine related to creatinine and volume showed a linear
      correlation to the CS2 air concentration. On the basis of these results the
      influence on the internal exposure of physical work load, dermal exposure and
      individual parameters (age, Brocaindex, disturbed skin barrier) was evaluated.
      Correlations between the TTCA values in the postshift urine and the individually
      measured CS2 concentrations were carried out separately for individual
      departments and persons with and without indications of a disturbed skin barrier.
      In order to be able to judge the individual internal exposure related to external
      exposure, a personal quotient was formed from the TTCA level in the urine and the
      CS2 air concentration measured on the same day (relative internal exposure RIE
      index = TTCA mg/g creatinine/CS2 in ppm). On investigating interindividual
      differences, higher relative internal exposures were found in persons with a
      heavy physical work load and more intensive skin contact. It could be shown for a
      large group of persons exposed to CS2 that a pathological skin condition leads to
      an increase in the dermal penetration rate of hazardous substances.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7622281
TI  - Bronchial responsiveness decreases in relocated aluminum potroom workers compared
      with workers who continue their potroom exposure.
AB  - We have compared the bronchial responsiveness (BR) of 12 aluminum potroom workers
      (index group) who were relocated due to work-related asthmatic symptoms (WASTH)
      and 26 subjects (reference group) with WASTH who continued to work in potrooms.
      The subjects were examined at regular intervals during a 2-year follow-up period.
      BR was expressed as the log-transformed dose-response slope [Ln(DRS 5)]. The
      monthly change in BR (delta BR) in the index group was -4.87 x 10(-2) compared
      with -1.58 x 10(-2) in the reference group. After adjustment for potential
      confounders, the difference between the index group and the reference group was 
      2.39 x 10(-2) (95% CI: -4.07 x 10(-2) to -0.71 x 10(-2)), i.e. 49% of the
      decrease in BR in the index group could be explained by the removal from
      exposure. No improvement in lung function was found in the index group compared
      with the reference group. The results indicate that the removal of potroom
      workers from exposure causes a decrease in BR.

PMID- 7622283
TI  - Socioeconomic factors and human cancer.
AB  - In spite of the many attempts made at various periods of human history to arrive
      at an equalitarian society by reducing differences between the rich and the poor
      and by redistributing wealth, social inequalities have not disappeared and even
      seem to be increasing worldwide. Inequalities in health represent some of the
      social inequalities present in our society and are one of their most convincing
      indices. In industrialized countries, it has been consistently shown that total
      incidence of and mortality from cancer are higher in less favored socioeconomic
      groups, mainly due to increased rates at certain sites. The differences observed
      between socioeconomic groups within industrialized countries are similar,
      although not identical, to those prevailing between industrialized and developing
      countries. Occupational risks are becoming a very serious problem in developing
      countries, largely as a consequence of the transfer of hazardous industries from
      highly industrialized countries where certain industries are judged to be
      unacceptable. A similar double standard is applied toward tobacco advertising and
      sales in the industrialized and developing countries.

PMID- 7622282
TI  - Human exposure to volatile organic compounds: a comparison of organic vapor
      monitoring badge levels with blood levels.
AB  - We undertook a study in Albany, New York, to investigate whether volatile organic
      compounds (VOCs) were measurable in the blood and in the breathing-zone air of
      people exposed to gasoline fumes and automotive exhaust. We sampled blood of 40
      subjects, placed organic vapor badges on 40 subjects, and obtained personal
      breathing-zone samples from 24 subjects. We limited this analysis to 19 subjects
      who wore the organic vapor badges for at least 5 h. VOC levels, as determined by
      the organic vapor badges, were highly correlated with blood levels of these same
      compounds. Using detection in blood as the gold standard, we found the badges to
      be more sensitive than conventional charcoal tube samples in detecting low levels
      of methyl tert-butyl ether (0.60 vs 0.08), toluene (0.95 vs 0.64), and o-xylene
      (0.85 vs 0.64). In this study, organic vapor badges provided data on VOC exposure
      that correlated with blood assay results. These organic vapor badges might
      provide a convenient means of determining human exposure to VOCs in epidemiologic
      studies.

PMID- 7622284
TI  - Microvessel density and vessel invasion in lymph-node-negative breast cancer:
      effect on recurrence-free survival.
AB  - Microvessel density (MVD) and blood and lymphatic vessel invasion (BLVI) were
      investigated with regard to their influence on the disease-free survival (DFS) in
      node-negative breast cancer patients. Paraffin embedded microsections of 230
      patients with T1,2 N0 breast cancer were immunohistochemically stained for factor
      VIII-related antigen. Every cluster consisting of more than highlighted
      endothelial cells was considered a countable microvessel. MVD was counted in 4
      fields of 0.25 mm2 each. All MVD values are given as value for the sum of 4
      fields of 0.25 mm2 each, that is, I mm2. BLVI was considered positive, when at
      least one tumor cell could be identified in a stained lumen. Out of 230 patients,
      49 experienced local or distant recurrence and had a mean MVD of 72.4/mm2,
      whereas 181 patients who lived without recurrent disease had a mean MVD of
      45.3/mm2. BLVI was negative in 6.2% of the cases with and in 93.8% of the cases
      without recurrent disease. BLVI was positive in 59.4% of the cases without and
      40.6% of the cases with recurrent disease. MVD and BLVI remained the only
      significant prognostic factors of DFS in the Cox-Model. Tumor size, histological
      grade, and hormonal-receptor status were not prognostically relevant in the Cox
      model. 10-year-DFS was 93.3% in BLVI-negative/MVD < or = 40/mm2 patients, 88.1%
      when MVD was high or BLVI was positive and 48.9% in BLVI positive/MVD < or =
      40/mm2 patients. Our present data indicate that MVD and BLVI identify a very-low
      risk group among node-negative breast cancer patients, who will not benefit from
      systemic adjuvant therapy. MVD and BLVI should be used as stratification criteria
      in clinical trails on node-negative breast cancer patients.

PMID- 7622285
TI  - Hereditary aspects of endometrial adenocarcinoma.
AB  - The importance of heredity in the etiology of endometrial cancer (EC) was
      examined in a series of 326 patients with EC diagnosed at age 60 years or less.
      If one or both of the proband's parents had died of cancer, a thorough family
      history of malignancies was studied. Altogether 291 cases with complete parental
      data were found. Nine kindred (3.1%) showed features compatible with the
      dominantly inherited cancer trait known as hereditary non-polyposis colorectal
      cancer (HNPCC). In another 9 cases, clustering of malignancies in 2 or more
      successive generations was indicative of familial cancer. Aspecific cancer
      aggregates were found in 112 probands' families, and family history was negative
      in 161 cases. No families had gynecological cancer as the only malignancy. HNPCC,
      the genetic etiology of which was recently revealed, seems to be an important
      risk factor for EC, indicating the significance of family-history investigations
      of all patients with EC. Colorectal carcinoma (CRC) was here associated with EC
      also in families with clusterings of malignancies, but in these families no
      typical features of any known hereditary cancer syndrome could be found. On the
      basis of the results of the present study, proper surveillance for colorectal
      cancer should be recommended for patients with endometrial carcinoma if they
      belong to a family with features indicative of HNPCC. Furthermore, healthy gene
      carriers in an HNPCC family also need careful surveillance for CRC, EC and
      perhaps for other extra-colonic malignancies typical for HNPCC. Prophylactic
      surgery should even be considered in these cases.

PMID- 7622286
TI  - Age as a prognostic factor in breast cancer: relationship to pathologic and
      biologic features.
AB  - The relationship of age with prognostic factors and outcome of breast cancer has
      long been controversial due to numerous confounding factors. In order to clarify
      the prognostic value of age, we analyzed a homogeneous population of 1,266
      patients treated for breast cancer at the same institution (mean follow-up: 62
      months). Three groups were compared: patients under 35 years of age, non
      menopausal patients over 35 years of age, and post-menopausal patients under the
      age of 70 years. A higher frequency of undifferentiated tumors, histoprognostic
      grade-3 cancer, microscopic lymph-node involvement and negative hormonal receptor
      status was observed in patients under 35 years. In addition, clinical but not
      anatomical tumor size was greater in young patients, suggesting higher stromal
      activity. Metastasis-free survival and overall survival were significantly poorer
      before 35 years. Differences were observed when patients were matched with regard
      to stage, anatomic size, histoprognostic grade, microscopic lymph-node
      involvement and receptor status. Multivariate analysis of both overall and
      metastasis-free survival demonstrated that age younger than 35 years was an
      independent risk factor. Younger women had a higher risk of local recurrence but,
      unlike older women, they did not experience any worsening of the already
      unfavorable outcome due to recurrence.

PMID- 7622287
TI  - EGFR gene amplification--rearrangement in human glioblastomas.
AB  - Immunostaining using an affinity-purified rabbit polyclonal antibody against the
      extracellular domain of the epidermal-growth-factor receptor (EGFR) showed over
      expression occurring in a fraction of tumor cells in 17 out of 18 human
      glioblastomas and in a majority of cells in 7 of the 18. Southern-blotting
      technique using a full-length EGFR cDNA probe showed a variable degree of
      amplification in 10 of the 17 glioblastomas, which was associated with EGFR over
      expression in each case. In 2 of the glioblastomas with EGFR gene amplification,
      a rearrangement of the gene affecting the extracellular domain of the receptor
      was identified and DNA sequence analyses revealed an identical deletion
      rearrangement of 801 base pairs between exons 2 to 7, resulting in an in-frame
      fusion of exons 1 and 8.

PMID- 7622288
TI  - Cell proliferation patterns and p53 expression in gastric dysplasia.
AB  - Gastric dysplasia (high-grade, HGD, and low-grade, LGD) and normal mucosa were
      tested for anti-p53, anti-Ki-67 and anti-PCNA monoclonal antibodies on paraffin
      sections, and for relative AgNOR area and number on semithin Epon-Araldite
      sections. The proliferative compartment in normal mucosa was restricted to the
      middle layer corresponding to the neck-isthmus region. In LGD and HGD there was
      an expansion of this compartment to the lower and upper layers of mucosa, and in
      HGD in particular to the upper layer. p53 was always negative in LGD as well as
      in normal mucosa, while it was positive in 34 out of 51 cases of HGD. The most
      discriminant variables between LGD and HGD were relative AgNOR area and the
      percentages of MIB-1, p53 and PCNA. In p53-positive HGD the highest percentages
      of PCNA and MIB-1 were in the middle and upper layers (PCNA) or the upper layer
      (MIB-1), while in p53-negative HGD cases cell proliferation was maximal in the
      middle layer, although also present in the upper layer. The majority of cases of
      LGD did not demonstrate cell proliferation in the upper layer, but 5 cases
      behaved similarly to the p53-negative HGD cases. No significant correlations were
      found among percentages of MIB-1 and of PCNA and relative AgNOR area and number.

PMID- 7622289
TI  - Establishment and characterization of an uveal-melanoma cell line.
AB  - A human uveal melanoma cell line (92-1) was established from a primary uveal
      melanoma, and has now been maintained in culture for over 2 1/2 years. Light
      microscopy of the cultured cells demonstrated extremely pleiomorphic cells with
      large prominent nucleoli. Cell proliferation was determined with a non
      radioactive propidium-iodide assay and indicated an in vitro doubling time of
      approximately 58 hr. Furthermore, the cell line was characterized by cytogenetic
      analysis, electron microscopy, immunocytochemistry and Northern blotting for HLA
      and c-myc-mRNA analysis. Cytogenetic analysis revealed numerical abnormalities of
      chromosome 8 and structural abnormalities of chromosome 6. By electron
      microscopy, different stages of melanosome development were observed.
      Immunocytochemical analysis demonstrated expression of the melanoma-associated
      antigen gp 100. Expression analysis of HLA antigens revealed a very low level of,
      in particular, the HLA-B locus products, which could be induced by interferon
      alpha or -gamma treatment. Likewise, Northern-blot experiments revealed decreased
      levels of HLA-B mRNA as compared with HLA-A. In addition, high levels of c-myc
      expression were observed. The phenotypic characteristics of the cultured cells
      indicate that we have established an uveal melanoma cell line. This now well
      characterized uveal melanoma cell line can be used in future studies.

PMID- 7622290
TI  - Multiple births and risk of breast cancer.
AB  - Data from a large, multicenter, population-based case-control study were analyzed
      to investigate the relation between multiple birth pregnancies and subsequent
      breast-cancer risk in the gravidas. Women less than 75 years old who had breast
      cancer were identified from statewide tumor registries in Wisconsin, western
      Massachusetts, Maine and New Hampshire. Controls aged less than 65 years were
      selected randomly from lists of licensed drivers, and controls aged between 65
      and 74 were selected randomly from lists of Medicare beneficiaries. Information
      on reproductive history and other factors was obtained by means of telephone
      interviews. After excluding nulliparous women, 5,880 case subjects and 8,217
      controls remained for analysis. Multiple birth pregnancies occurred in 146 cases
      and 218 controls. Adjusted for the number of full-term pregnancies and other
      confounders, the odds ratio (OR) for any multiple birth pregnancy was 0.94 (95%
      confidence interval, 0.75 to 1.17). The null association between multiple birth
      pregnancies and breast cancer remained if the mother's first pregnancy or last
      pregnancy resulted in a multiple birth. In addition, no trend in risk emerged for
      age at first multiple birth or time since last multiple birth. While other
      investigators have suggested biological mechanisms to explain both protective and
      detrimental effects of multiple births and subsequent development of breast
      cancer, this study does not support either assertion.

PMID- 7622291
TI  - Evidence that a low-fat diet reduces the occurrence of non-melanoma skin cancer.
AB  - The effect of a low-fat diet on occurrence of non-melanoma skin cancer was
      examined in a 2-year dietary intervention trial. A total of 101 skin-cancer
      patients were randomized either to a control group that consumed, on average, 38%
      of caloric intake as fat, and in which no changes in dietary habits were
      introduced, or to a low-fat dietary-intervention group, in which patients were
      instructed to limit their calories from fat to 20% of total caloric intake.
      Patients were examined at 4-month intervals by dermatologists blinded to their
      dietary assignments. Nutrient analyses, conducted at each of the 4-month follow
      up visits, indicated that the % calories of fat consumed in the intervention
      group had been reduced to 21% at 4 months and remained below this level
      throughout the 2-year period. There were no significant differences in total
      calories consumed, or in mean body weights, between the control and the
      intervention groups. Nor were there significant group differences in P/S ratios
      until month 24. Numbers of new skin cancers treated at each examination were
      analyzed in 8-month periods of the 2-year study. Comparisons of skin-cancer
      occurrences revealed no significant changes in the control group from baseline
      values. However, cancer occurrence in the low-fat intervention group declined
      after the first 8-month period and reached statistical significance by the last 8
      month period. Patients in this group had significantly fewer cancers in the last
      8-month period than did patients in the control group. In addition, there was a
      significant reduction in the number of patients developing skin cancer in the
      last 8-month period, as compared with the first 8-month period, within the low
      fat intervention group. There were no significant changes in the control group.
      These data indicate that a low-fat diet can significantly reduce occurrence of a
      highly prevalent form of cancer.

PMID- 7622292
TI  - Comparison of cell-cycle phase perturbations induced by the DNA-minor-groove
      alkylator tallimustine and by melphalan in the SW626 cell line.
AB  - Tallimustine or N-deformyl-N-[4-N-N,N-bis(2-chloroethylamino)benzoyl], a
      distamycin-A derivative (FCE 24517), is a novel anti-cancer agent which alkylates
      N3 adenine in the minor groove of DNA. The cell-cycle phase perturbations induced
      by the drug were investigated and compared with those caused by melphalan (L-PAM)
      in SW626 human ovarian-cancer cells. By coupling bromodeoxyuridine (BUdR)
      immunoreaction with biparametric flow-cytometric (FCM) analysis, we investigated
      the cell-cycle phase perturbation induced by tallimustine or L-PAM, considering
      separately the cells which, during the 1-hr treatment, were in the S phase or in
      G1-G2/M phases of the cell cycle. L-PAM delayed the S-phase progression of cells
      exposed to the drug when they were in S phase, with a consequent accumulation of
      cells as soon as they reached the G2 phase. In contrast, the S-phase cells
      treated with tallimustine were not perturbed during the DNA-synthesis phase
      progression, and were blocked in G2 only after they had passed through the G1/S
      transition of a new cell cycle. In cells which were in G1 or G2/M phases during
      drug treatment, tallimustine and L-PAM caused similar accumulation in G2. The
      differences in the cell-cycle perturbation caused by tallimustine and L-PAM may
      well be related to the different DNA damage the 2 drugs produced. These findings
      emphasize the different properties of DNA-minor-groove alkylating agents and
      conventional ones.

PMID- 7622293
TI  - Purine enzyme profile in human colon-carcinoma cell lines and differential
      sensitivity to deoxycoformycin and 2'-deoxyadenosine in combination.
AB  - Different cell lines, 2 from human colon carcinoma (LoVo and HT29) and 1 from
      Chinese hamster ovary (CHO K-I), were examined to assess the effect of
      deoxycoformycin (dCF), an inhibitor of adenosine deaminase (ADA), and 2'
      deoxyadenosine (dAdo) on their growth. When used alone, neither dCF or dAdo were
      cytotoxic for the 3 cell lines, while their combination caused inhibition of cell
      growth, with the following sensitivity: CHO K-I > LoVo > HT29. We studied the
      pattern of enzymatic activities involved in the metabolism of dAdo in the 3 cell
      lines. The phosphorylation of dAdo by adenosine kinase appears to play a central
      role in the toxicity of the deoxynucleoside in combination with dCF. In fact, CHO
      K-I cells, which are the most sensitive, possess the highest level of this
      enzyme. Moreover, the cytotoxic effect was almost completely reversed in the 3
      cell lines when inhibitors of adenosine kinase, such as 5'-amino-5'
      deoxyadenosine and iodotubercidine, were added to the culture medium together
      with dCF and dAdo. In addition, baby hamster kidney (BHK) adenosine-kinase
      deficient (AK-) cells were highly resistant to this treatment. Uptake inhibition
      of dAdo using dipyridamole also caused reversal of the toxicity. The AMP and
      deoxyAMP dephosphorylating activities, much lower in the CHO K-I cells, also
      appear to play a central role in the toxicity of dAdo when adenosine deaminase is
      inhibited. However, our data suggest that other factors may modulate the toxic
      effect, such as S-adenosyl-homocysteine-hydrolase inhibition by dAdo at high
      concentrations.

PMID- 7622294
TI  - Correlation between the sensitivity or resistance to IL-2 and the response to
      cyclophosphamide of 4 tumors transplantable in the same murine host.
AB  - We have studied the anti-tumor response to cyclophosphamide (CTX) in DBA/2 mice
      transplanted s.c. with 4 tumors exhibiting different responses to IL-2: ESb
      lymphoma and Friend leukemia cells (non-responsive or poorly responsive,
      respectively), p11-R-Eb and Eb lymphoma cells (both highly responsive to IL-2).
      CTX injections on days 7, 14 and 21 resulted in a significant anti-tumor response
      in mice transplanted s.c. with Friend leukemia cells or ESb cells, whereas no
      anti-tumor effect was observed in mice injected with Eb or p11-R-Eb cells. All 4
      tumor cell lines were equally sensitive to the cytotoxic effects of mafosfamide,
      an in vitro active analogue of CTX. To define the host mechanisms responsible for
      the lack of an anti-tumor effect of CTX in mice transplanted with IL-2-responsive
      tumors, we studied several aspects of the spontaneous or IL-2-induced anti-tumor
      response in mice transplanted with p11-R-Eb cells. Injection of monoclonal
      antibodies (MAbs) to IFN-gamma completely abolished the anti-tumor effects of IL
      2. Using a Winn assay, clear-cut anti-tumor activity was found in spleen cells
      from mice transplanted with the IL-2-responsive tumors. This activity was
      abolished by CTX, which also abrogated the anti-tumor response to IL-2 in mice
      injected with p11-R-Eb cells. Our results indicate an inverse correlation between
      sensitivity to IL-2 and response to CTX and emphasize the importance of initial
      host-tumor interaction in determining the type of response to IL-2 or CTX.

PMID- 7622295
TI  - Apoptosis of a fibrosarcoma induced by protein-free culture involves DNA cleavage
      to large fragments but not internucleosomal fragmentation.
AB  - A murine fibrosarcoma clone, Gc-4 SD, grows depending on fetal calf serum. In MTT
      assay, protein-free cultivation resulted in a reduction of the viable cell number
      time-dependently. Electron-microscopic and flow-cytometric analyses revealed that
      the reduction in growth was accompanied by the appearance of apoptotic cells.
      However, no internucleosomal fragmentation was observed even after SI-nuclease
      treatment. On the other hand, pulse field gel electrophoresis revealed that
      cleavage of DNA into high-molecular-weight fragments estimated as 50 to 150
      kilobase pairs (kbp), with a peak of 100 kbp, was found in the serum-deprived
      cells. Large fragments disappeared from the DNA extracts when the smaller cells
      with high blue fluorescence with Hoechst 33342 were removed by flow cytometry,
      suggesting direct correlation between the large DNA fragmentation and apoptosis.
      The addition of aurintricarboxylic acid neither abolished the large DNA
      fragmentation nor inhibited the reduction in the number of viable cells. Both
      cycloheximide and actinomycin D enhanced the reduction in the number of viable
      cells as well as the large DNA fragmentation. These results suggest that
      apoptosis of a fibrosarcoma induced by protein-free culture involves a specific
      endogenous endonuclease, which may be distinct from and independent of the ATA
      sensitive endonuclease producing internucleosomal DNA fragmentation.

PMID- 7622296
TI  - Pharmacokinetics and anti-tumor activity of vincristine encapsulated in
      sterically stabilized liposomes.
AB  - Vincristine is used clinically for the treatment of various types of cancer.
      Recent significant therapeutic improvements obtained by entrapping anthracyclines
      in sterically stabilized liposomes raised the question whether the therapeutic
      index of vincristine can be similarly increased by formulation into such long
      circulating liposomes. Encapsulation of vincristine in sterically stabilized
      liposomes (SL-VCR) prolonged the drug's distribution phase plasma half-life in
      rats from 0.22 to 10.5 hr. There was no significant difference in LD50 (> < or =
      2.5 mg/kg, i.v.), but mice given sublethal doses of SL-VCR experienced
      significantly less weight loss than those given the same dose of free drug.
      Compared to free drug, SL-VCR was most effective against i.p. or s.c. implanted
      tumors. However, i.v. tumor inoculation nullified the therapeutic advantage of
      encapsulation. A single i.v. 2 mg/kg dose of SL-VCR increased the life span of
      mice bearing i.v. implanted P388 cells by only 44%, while the life span of i.p.
      P388 implanted mice was increased by 199%. In an s.c. implanted murine colon
      carcinoma, multiple doses of free drug did little to slow the growth of the
      tumors, but SL-VCR was able to produce long-term survivors in several dose
      regimens. These results indicate that prolonged circulation time increases the
      therapeutic index of VCR entrapped in liposomes against s.c. or i.p. implanted
      tumors, but does not improve the drug's activity against rapidly growing i.v.
      disseminated leukemias.

PMID- 7622297
TI  - Rodent model of systemic mammary tumor disease by surgical removal of the
      spontaneously metastasizing SMT2A mammary carcinoma: inhibitory effect of the
      stable prostacyclin analogue cicaprost on occult metastasis.
AB  - Cicaprost, a stable prostacyclin analogue, has been shown to be anti
      metastatically active in a series of metastasizing rodent tumors. Start of
      treatment with cicaprost immediately before tumor implantation was a
      characteristic feature of our previous investigations. We have reported that in
      rats bearing mammary-fat-pad-implanted SMT2A mammary carcinoma, cicaprost
      treatment starting before tumor implantation led to a strong decrease in the
      number of lung metastases. In order to determine the effect on occult tumor
      metastasis, the present study examined the effect of starting treatment when
      tumor metastasis is already present. Cicaprost in daily oral doses of 0.1 mg/kg
      given from day 10 to day 32 reduced the number of lung metastases by about 75%
      compared with the control, whereas surgical removal of palpable primary tumors on
      day 5 or day 10 failed to influence lung metastasis. Using different treatment
      schedules, a pronounced reduction of the number of lung metastases was achieved
      by administration of cicaprost until the end of the experiment (from day 5 to day
      35), whereas short-term treatments (from day 5 to day 15 or to day 25) were
      without significant effect. In rats whose SMT2A tumors were surgically removed 10
      days after tumor implantation, there was a strong decrease of lung metastases by
      cicaprost given from day 20 to day 36. In addition to its inhibitory potential in
      animals with advanced tumor disease, cicaprost showed anti-metastatic action when
      used in peri-operative treatment of animals whose primary tumors had been
      removed. In conclusion, the present results demonstrate that cicaprost exhibits
      strong anti-metastatic activity in the SMT2A rat mammary-carcinoma model with
      treatment started when occult tumor metastases are already present. Results also
      indicate that direct effects on tumor cells may contribute to the anti-metastatic
      action of cicaprost in spontaneously metastasizing tumors.

PMID- 7622298
TI  - Inhibition by dehydroepiandrosterone of growth and progression of persistent
      liver nodules in experimental rat liver carcinogenesis.
AB  - Dehydroepiandrosterone (DHEA) inhibits the development of early pre-neoplastic
      lesions and prevents tumor development in various tissues when given to animals
      during the initiation/promotion stages of carcinogenesis. Our purpose was to
      evaluate whether DHEA can also arrest the growth and progression of late lesions,
      such as persistent nodules (PNs) of rat liver. Male F344 rats were subjected to
      initiation by diethylnitrosamine followed by selection according to the
      "resistant hepatocyte" (RH) protocol. Fifteen weeks after initiation, when PNs
      were present in the liver, the rats were fed a diet with/without 0.6% DHEA for a
      maximum of 15 weeks. Glucose-6-phosphate dehydrogenase (G6PD) activity was 17- to
      20-fold higher in PNs than in normal liver 15-30 weeks after initiation. It
      significantly decreased, in both liver and PNs, 16 hr after starting DHEA
      feeding. Further DHEA feeding for 3-15 weeks decreased G6PD activity by 55-58% in
      both tissues. Eight weeks after starting DHEA, a fall in the proportion of
      labeled cells, after continuous contact with 3H thymidine for 7 days, was found
      in nodules. Treatment for 15 weeks with DHEA caused a marked decrease in the
      number of nodules per liver, as well as in the incidence of PNs with diameters of
      3-6 and > 6 mm, respectively, while it did not affect PNs with diameters < 3 mm.
      Nodules showing patterns of malignant transformation were present in 40% of rats
      not treated with DHEA, but not in DHEA-treated rats. All of 8 surviving rats not
      treated with DHEA had carcinomas at the 56th week, while only 1 out of 4
      surviving rats treated with DHEA had carcinoma. These data indicate that DHEA
      inhibits G6PD activity in rat liver and in PNs in vivo. This is associated with
      growth restraint of PNs and results in inhibition of their progression to
      malignancy.

PMID- 7622300
TI  - Induction of 2.5 OAS gene expression and activity is not sufficient for IFN-gamma
      induced neuroblastoma cell differentiation.
AB  - We showed earlier that interferon-gamma is a powerful inducer of differentiation
      of human neuroblastoma (NB) cells. Although 2',5' oligo-adenylate synthetase (2,5
      OAS) may play a role in mediating the anti-proliferative and/or differentiative
      effects of interferons (IFNs), direct evidence is lacking. We have investigated
      gene and protein expression of the 4 different 2,5 OAS isoforms and their
      cumulative enzymatic activity in a previously characterized IFN-gamma-sensitive
      human NB cell line, LAN-5. Analysis of total and poly(A)+ RNA by Northern blot
      and RT-PCR indicated that expression of the mRNA coding for the 40-, 46-and 69
      kDa isoforms was induced in a time- and dose-dependent manner, reaching a maximum
      after a 36-hr treatment with 1000 IU/ml of IFN-gamma. In the absence of
      treatment, only the mRNA for the 69-kDa isoform was detectable by RT-PCR.
      Inhibition of transcription with actinomycin D showed that 2,5 OAS mRNA was quite
      stable, with a half-life of about 4 hr. With respect to the protein content, no
      2,5 OAS isoform was present in proliferating LAN-5 cells; following IFN-gamma
      treatment, the 100-, 69-and 46-kDa isoforms became detectable. Accordingly, 2,5
      OAS enzymatic activity, virtually undetectable in untreated LAN-5 cells,
      increased up to 132 pmol oligoadenylate/micrograms protein/hr after 48 hr of
      treatment, then slowly decreased, remaining detectable up to 96 hr. However, the
      2,5 OAS proteins required an exogenous activation by synthetic dsRNA to exert
      enzymatic activity. It is therefore conceivable that they do not play a
      biological role in NB cell functions. Moreover, an increase in 2,5 OAS enzymatic
      activity was also observed in NB cells resistant to the differentiation-promoting
      activity of IFN-gamma, further suggesting that 2,5 OAS induction was not
      sufficient to trigger IFN-gamma-dependent neuronal maturation. Furthermore, other
      differentiation-inducing agents, such as retinoic acid and cytosine arabinoside,
      or complete proliferative arrest produced by serum deprivation, failed to enhance
      2,5 OAS activity, thus indicating that the 2,5 OAS system is not directly
      involved in mediating other differentiative pathways of NB cells.

PMID- 7622299
TI  - Mitochondria-bound hexokinase as target for therapy of malignant gliomas.
AB  - Hexokinase plays an important role in glucose-utilizing tissues like normal brain
      and cancers. In these tissues, hexokinase (HK) is mainly bound to mitochondria
      (mHK). Our objectives were to evaluate total HK (tHK) activity and mHK fraction
      in gliomas and to determine whether mHK binding could be targeted for therapy.
      Tumors were obtained from 26 patients and 13 were xenografted. HK, lactate and
      ATP were measured in cytosol and mitochondria extracts. The tHK expressed in
      mU/mg protein were 147 +/- 19 and 78 +/- 12, in fresh gliomas and xenografts,
      respectively, and of 489 in the normal brain. The mHK fraction was 76% in normal
      brain, 74 +/- 4% in fresh tumors and 53 +/- 6% in xenografts. Lactate/mHK ratios
      were higher in gliomas than in normal brain. The ATP was 10, 52 +/- 31 and 19 +/-
      8 nmol/mg protein in normal brain, xenografts and fresh gliomas respectively.
      Loss of one copy of chromosome 10 which carries the HK1 gene, was evidenced in 11
      of the 13 xenografted gliomas. The anti-tumor effect of lonidamine (LND), which
      affects glycolysis in interfering with mHK activity, was tested in nude mice
      bearing 4 gliomas. LND (125 mg/kg, given i.p., twice daily for 5 days) led to a
      growth inhibition of TG-7-RO of 72%, with 2-fold growth retardation, and had no
      effect for TG-8-OZ. Intermediate LND-sensitivities for TG-11-DU and TG-10-PY were
      noted. The LND-sensitivity was correlated with the mHK activity (R2 = 0.73) and
      mHK fraction (R2 = 0.88). HK binding to mitochondria is a key of glycolysis in
      malignant gliomas, and targetting this binding with appropriate agents could be
      an effective therapeutic approach.

PMID- 7622302
TI  - Microsatellite instability in primary and metastatic colorectal cancers.
AB  - Microsatellite instability characterizes a sub-set of sporadic colorectal cancers
      (CRCs) as well as CRCs from patients with hereditary non-polyposis colorectal
      cancer (HNPCC). In order to clarify when the cells acquire a replication-error
      phenotype (RER) during colorectal-tumor progression, we examined the incidence of
      RER in 80 primary tumors and 36 liver metastases at 8 microsatellite loci; 1 mono
      , 5 di-, 1 tetra- and 1 pentanucleotide. RER were detected in 20.1% (17/80) of
      primary tumors, including 5 tumors showing RER at 2 or more loci (RER2), while
      the incidence of RER in liver metastases (22.2%, 8/36) was almost the same as
      that in primary tumors, and there was only one RER2 case in metastases. There
      were 3 cases in which both primary tumors and liver metastases had the same type
      of RER at the same locus, and there were 2 cases that showed RER in primary
      tumors but not in liver metastases. In contrast, there was no case in which RER
      was detected in a metastasis but not in the corresponding primary tumor. The RER
      phenotype did not show correlation with any clinicopathological parameters of
      cancer-cell aggressiveness, such as clinical staging, histological grade and
      survival. These results indicate that a sub-set of CRCs acquire the RER phenotype
      in the relatively early stages of colorectal carcinogenesis, and that the RER
      phenotype is not associated with aggressiveness of CRCs.

PMID- 7622303
TI  - Detection of MAGE-4 protein in lung cancers.
AB  - Expression of genes of the MAGE family, which encode tumor-rejection antigens
      recognized on HLA-AI and -Cw1601 by cytotoxic T lymphocytes (CTL), was
      investigated in lung cancers at the mRNA [MAGE-1, -2, -3/-6, and -4 (4a and/or
      4b)] and protein (MAGE-4) levels. MAGE-1, -2, -3/-6 and -4 genes were expressed,
      respectively, at the mRNA level in 6, 7, 20 and 7 of 53 lung cancers (50 non
      small-cell lung cancers and 3 small-cell lung cancers) by the reverse
      transcription-polymerase chain reaction (RT-PCR) method. Polyclonal antibody (Ab)
      and monoclonal antibody (MAb) against recombinant MAGE-4b protein were developed
      to detect MAGE-4 protein. Both the polyclonal Ab and the R5 MAb recognized a 45
      kDa protein in extracts of MAGE-4 mRNA-positive lung cancers, and showed no
      apparent cross-reactivity with the other MAGE gene products except with MAGE-4a
      by immunoblot analyses and transfection experiments. MAGE-4 protein was detected
      on 13 of 44 (30%) lung cancers (18 to 55,989 pg/mg) by ELISA with the polyclonal
      Ab and R5 MAb. These 13 lung cancers consisted of 6 of 6 MAGE-4 mRNA-detectable
      and 7 of 38 MAGE-4 mRNA-undetectable lung cancers. Histologically, these
      comprised 7 of 10 squamous-cell carcinomas, 4 of 30 adenocarcinomas and 2 of 3
      small-cell lung cancers. The proportions of MAGE gene-positive samples, at both
      the mRNA and protein levels, correlated with the size of the primary tumors and
      with regional node involvement. These results should provide important
      information on specific immunotherapy of lung cancers using MAGE gene products.

PMID- 7622301
TI  - Composition of ether-linked sub-classes of glycerophospholipids in clones with a
      different metastatic potential isolated from a murine fibrosarcoma line (T3
      cells).
AB  - An increase of ether-linked sub-classes of choline and ethanolamine
      glycerophospholipids has been shown in different types of tumor cells, and
      correlated with some of their specific biological parameters. In the present
      study, we examined the composition of ether-linked lipids in a series of clones
      with a different lung-colonizing potential isolated in our laboratory from a
      highly metastatic fibrosarcoma line (T3 cells). We found good correlation between
      the metastatic potential of T3 isolates and increased proportions of both
      alkylacyl and alkenylacyl subclasses in choline glycerophospholipids (CGP).
      Moreover, propagation of a weakly metastatic T3 clone in tissue culture led to
      the emergence of a sub-clone which expressed high metastatic potential together
      with a high level of alkylacyl and alkenylacyl CGP. No differences were found in
      the alkylacyl and alkenylacyl-ethanolamine glycerophospholipids (EGP) between the
      strongly and weakly metastatic T3 clones. We discuss the accumulation of
      alkylacyl and alkenylacyl CGP in metastatic cells for its possible role in
      metastatic diffusion by generation of platelet-activating factor (PAF).

PMID- 7622304
TI  - Predictive value of statin, a G0-associated cell cycle protein, in childhood
      acute lymphoblastic leukemia.
AB  - Blast cells of 71 children with newly diagnosed acute lymphoblastic leukemia
      (ALL) were examined with a novel monoclonal antibody (MAb), S-44, immunoreactive
      to statin, a nuclear protein specifically expressed in non-proliferating cells.
      The statin labeling index (LI) varied greatly from case to case and ranged from
      0.3% to 86%, with a mean value of 10%. The degree of statin LI correlated
      inversely with the expression of Ki-67. When patients were subdivided according
      to whether the statin LI was higher or lower than the mean value, patients with
      higher statin LI did not respond to chemotherapy and survived for a shorter
      period of time. Our results suggest that labeling of statin with the S-44 MAb is
      a useful prognostic marker of the cytotoxic effects of anti-cancer drugs in
      patients with ALL.

PMID- 7622305
TI  - Expression of galectin-1 in normal human thyroid gland and in differentiated and
      poorly differentiated thyroid tumors.
AB  - We previously reported that galectin-1 gene expression increases up to 100-fold
      in oncogene-transformed rat thyroid cells compared with their normal counterparts
      and that the relative mRNA levels correlate with the degree of malignancy. In the
      present study we investigated whether galectin-1 is differentially expressed in
      human thyroid neoplasms, which range from well-differentiated tumors to
      undifferentiated anaplastic carcinomas. We analyzed 74 human thyroid specimens of
      neoplastic, hyperproliferative and normal tissues and several tumor cell lines.
      Galectin-1 mRNA and protein levels were higher in 6 thyroid carcinoma-derived
      cell lines than in normal thyroid primary cultures and adenoma cells. Galectin-1
      mRNA levels increased in 28/40 papillary carcinomas and in 6/7 anaplastic
      carcinomas compared with normal or hyperplastic thyroid. Conversely, galectin-1
      expression was unaffected in follicular carcinomas and benign adenomas.
      Immunohistochemical analysis of normal thyroid and papillary carcinoma sections
      revealed a higher content of galectin-1 protein in neoplastic follicular cells
      than in normal cells.

PMID- 7622306
TI  - p53 antibodies in the sera of lung cancer patients: comparison with p53 mutation
      in the tumour tissue.
AB  - This study examined the sensitivity and specificity of serum auto-antibodies to
      p53 protein as a non-invasive marker of p53 genetic alterations or protein
      accumulation in lung cancer cases. A sensitive ELISA to detect serum p53
      antibodies was developed and used to examine sera from 186 patients undergoing
      pulmonary surgery for a suspected lung cancer. Target antigens in ELISA were wild
      type p53 protein and 5 peptides covering the N- and C-terminal parts of the
      protein. Sixteen sera were positive for serum p53 antibodies in both ELISAs and
      all were among the 136 patients with confirmed primary lung carcinoma. Of 50
      patients with other pulmonary diseases, none had p53 antibodies. In 92 cancer
      patients exons 5 to 8 of the p53 gene were examined for mutations by denaturing
      gradient gel electrophoresis and direct sequencing of PCR products. Forty-seven
      tumours had a p53 mutation and 7 (15.2%) of these were positive for p53
      antibodies. Two patients had serum antibodies but no detectable mutation in exons
      5 to 8. Frequencies of p53 mutations and serum antibodies were higher in squamous
      cell carcinoma patients than in adenocarcinoma. Accumulation of p53 protein in
      tumour tissue was observed in 32 patients, but only 5 were positive for p53
      antibodies. In conclusion, serum p53 antibodies were detected only in a
      proportion of lung cancer cases, but the majority were specifically associated
      with a detectable p53 mutation in the tumour.

PMID- 7622308
TI  - Sequential p53 mutation analysis of pre-invasive and invasive head and neck
      squamous carcinoma.
AB  - Single-stranded conformational polymorphism (SSCP) and direct sequencing were
      performed on uninvolved mucosa, severe dysplasia and invasive carcinoma samples
      from 20 patients with head and neck squamous carcinoma. Seven (35%) of the non
      invasive lesions and 15 (75%) of the invasive carcinomas manifested p53
      mutations. Although the majority of mutations were mis-sense, resulting in single
      amino acid substitution, a silent mutation encoding for the same amino acid and 2
      non-sense mutations encoding a stop codon were also observed. Mutations in
      invasive carcinoma were mostly in exon 8 and involved codons 296, 288 and 298;
      non-invasive lesions showed more mutations at exons 5 to 7. Five lesions showed
      simultaneous mutations in 2 different exons; in 3 both non-invasive and invasive
      carcinomas showed primary mutation at exons 5 to 7, and invasive carcinoma showed
      a secondary mutation at exon 8. Different codon mutations in the same exon
      between dysplastic and the corresponding carcinoma samples were found in 2 cases.
      p53 alterations were not observed in any of the normal mucosa samples. No
      apparent association between p53 mutations and conventional clinicopathologic
      parameters, including DNA content, was found in this cohort. Our study indicates
      that (i) p53 alteration is an early event in the genesis of a subset of head and
      neck squamous carcinomas, (ii) normal mucosa within the resected specimens lacked
      p53 mutation, (iii) sequential mutations of different exons of the p53 gene
      suggests accumulation of genetic alterations during the neoplastic transformation
      of these lesions and (iv) the difference in codon mutation of the same exon
      between dysplastic and corresponding carcinoma suggests an independent clonal
      development.

PMID- 7622307
TI  - Increased expression of the NME1 gene is associated with metastasis in epithelial
      ovarian cancer.
AB  - The genetic events involved in the development of metastases of epithelial
      ovarian cancer are largely unknown. One gene postulated to play a role in tumour
      metastasis suppression is NME1 (nm23-H1), and an inverse relationship between
      NME1 expression and metastatic potential has been observed for some solid
      tumours. In this study we have investigated the levels of mRNA expression of the
      2 isoforms of the NME gene, NME1 and NME2. A maximum of 45 tumours samples from
      33 patients were available for Northern blot analysis. We observed variable
      levels expression of NME1 and NME2 mRNA. The average level of NME1, but not NME2,
      mRNA expression was statistically higher in metastatic biopsies when compared
      with primary tumour biopsies. To examine the possible tumour suppressor gene role
      of NME1 in ovarian tumours, 76 patients were investigated by Southern blot
      analysis to determine the rate of allelic deletion. Allele loss at 5 other
      chromosome 17 loci (D17S5, TP53, NF1, D17S74, D17S4) was also evaluated for many
      of these 76 patients. Allele loss was observed in 22/30 (73%) informative
      patients at the NME1 locus. We also observed high rates of allele loss at the
      other loci evaluated. No correlations with clinical stage, histological subtype
      or patient survival were observed in either mRNA or DNA analyses. We have
      established that tumour progression in ovarian cancer is accompanied by over
      expression of the NME1 gene; however, despite high rates of allele loss at the
      NME1 locus, the concept that NME1 may be a candidate tumour suppressor gene in
      ovarian cancer cannot be confirmed by this study.

PMID- 7622309
TI  - c-erbB growth-factor-receptor proteins in ovarian tumours.
AB  - Immunohistochemical expression of EGF-R, c-erbB-2 and c-erbB-3, members of the
      type-1 family of receptor tyrosine kinases, were investigated in 67 primary
      ovarian-tumour samples (46 malignant, 8 borderline and 13 benign), and related to
      tumour clinicopathological features. The incidence of all 3 receptor proteins was
      highest in overtly malignant tumours. No significant correlations were observed
      between either EGF-R or c-erbB-3 and clinical parameters such as tumour stage,
      differentiation or extent of debulking surgery, but c-erbB-2 was significantly
      associated with several indicators of prognosis, including early stage and
      good/moderate differentiation in optimally debulked tumours. Multiple expression
      of c-erbB receptor proteins was also significantly higher in malignant tumours
      compared with borderline and benign tumours. Early-stage tumours were also more
      likely to express multiple c-erbB-receptor proteins than were late-stage tumours.
      Co-expression of EGF-R with c-erbB-2, and c-erbB-2 with c-erbB-3 was
      significantly greater in malignant tumours than in borderline or benign tumours,
      and within the malignant tumour group, positive associations were observed
      between EGF-R and c-erbB-3, also between c-erbB-2 and c-erbB-3. Because of the
      evidence of increased expression of individual c-erbB proteins as well as
      multiple expression of this family of growth-factor receptors in malignant
      ovarian tumours, we hypothesize that stimulation by the appropriate ligands may
      confer a selective advantage to cells expressing more than one receptor.
      Increased expression of c-erbB growth-factor receptors in malignancy may mediate
      increased propensity for tumour development.

PMID- 7622313
TI  - The politics of health care reform in the United States, 1992-1994: a historical
      review.
AB  - In an analysis of the sociopolitical context of the debate on health care reform
      in the United States, the author focuses on the political events that led to the
      election of a Democratic administration in 1992; the evolution of the White House
      task force on health care reform and the interests and positions it represented;
      the connection between economic and political power in the United States; and the
      reasons for the defeat of the health care reform proposal. This historical
      analysis questions some of the dominant interpretations of the failure to reform
      health care, which assume that the U.S. population was not yet ready for these
      reforms.

PMID- 7622312
TI  - Expression of the MAGE gene family in primary and metastatic human breast cancer:
      implications for tumor antigen-specific immunotherapy.
AB  - Some human tumors express known antigens that can be utilized as targets for
      specific immunotherapy. An absolute requirement for the efficacy of this
      therapeutic strategy is an adequate expression of the candidate antigen by all
      cells of the primary and metastatic tumor. To examine the presence and
      distribution of tumor-associated antigens in metastatic breast cancer, we used
      PCR analysis and ethidium bromide staining to test the expression of genes of the
      MAGE family in 28 primary tumors and related metastatic samples. Overall, samples
      obtained from 7 of 28 patients revealed positive. However, 2 of 3 primary tumors
      positive for MAGE-1 and/or MAGE-3 had corresponding negative metastatic lesions.
      On the contrary, 4 of the 25 MAGE-negative primary tumors gave rise to positive
      metastatic nodes. Our results confirm in vivo, at the molecular level, the tumor
      antigen heterogeneity previously observed at the cellular level by in vitro
      analysis. Our data strongly suggest that, at least in patients with breast
      cancer, multiple different antigens would be required to optimize the recognition
      of neoplastic cells in immunotherapeutic protocols using MAGE products as target
      antigens.

PMID- 7622310
TI  - Allelic loss at 1p and 19q frequently occurs in association and may represent
      early oncogenic events in oligodendroglial tumors.
AB  - The molecular mechanisms underlying the genesis and progression of
      oligodendroglial tumors are poorly understood, since only restricted information
      on loss of heterozygosity from isolated cases is available. The commonest
      alterations appear to involve deletion of 1p and 19q, while loss of
      heterozygosity for 9p, chromosome 10 or epidermal growth factor receptor gene
      amplification have been described in single tumors. We have applied restriction
      fragment length polymorphism analysis to 14 loci covering chromosome 1 and 7 loci
      on chromosome 19 in a series of 25 tumors with an oligodendroglial component to
      determine precisely the participation of these suppressor genes in the genesis of
      tumors. Twenty-two and 19 of the 25 samples displayed LOH at 1p and 19q,
      respectively, and both anomalies were detected in association in 17 samples,
      including low- and high-grade oligodendrogliomas as well as mixed oligo
      astrocytomas. Our findings suggest that inactivation of tumor suppressor genes
      located on 1p and 19q represent cooperative alterations occurring at early stages
      of oncogenic transformation of oligodendroglial neoplasms.

PMID- 7622311
TI  - Can a test for E6/E7 transcripts of human papillomavirus type 16 serve as a
      diagnostic tool for the detection of micrometastasis in cervical cancer?
AB  - Tissue from 11 cases of cervical cancer positive for human papillomavirus (HPV)
      type 16 DNA and 69 pelvic lymph nodes from the same patients were examined for
      HPV 16 DNA and mRNA from the E6/E7 genes. Five of the tumors were squamous, 3
      adeno- and 3 adenosquamous carcinoma. From the primary tumors and the extirpated
      lymph nodes DNA and RNA or mRNA was subjected to PCR and RT-PCR. Three
      transcription profiles (only E6*I, E6*I and E6*II or full-length E6-E7 plus both
      of the spliced transcripts) were found in all of the 11 HPV 16 DNA-positive
      primary tumors. From the total of 69 lymph nodes analyzed 28 were positive for
      mRNA. HPV 16 DNA was found in 7 additional samples. Cytokeratin was found in 19
      of these lymph nodes, indicating epithelial origin of tumor cells. Only 1 patient
      had 2 metastases evidenced by histology. These were both positive for HPV DNA and
      mRNA. The finding of HPV DNA, mRNA and cytokeratin in lymph nodes of patients
      with cervical cancer should be an indication of lymphogenically driven
      micrometastases of the tumor. The HPV mRNA assay should offer higher specificity
      than the DNA test since mRNA can be found in live cells only, while HPV DNA also
      can originate from dead cell material sequestered in the lymph nodes.

PMID- 7622314
TI  - The development of quasi-markets in welfare provision in the United Kingdom.
AB  - In the late 1980s, governments in many western economies began to introduce
      competition between public agencies providing health, education, and other forms
      of social welfare. Government became a contracting agency separating funding from
      provision. The United Kingdom went farthest in legislation passed between 1988
      and 1990. The authors review some possible explanations for this fundamental
      change. The article draws on public choice theory and broader political science
      approaches and reviews the evidence on the impact of the changes. The gains from
      these changes may be small, and the result may be only the build up of pressure
      for more spending in the longer term.

PMID- 7622315
TI  - Challenges to professional autonomy in the United Kingdom? The perceptions of
      general practitioners.
AB  - Theoretical analysis has suggested that so-called threats to professional
      autonomy in the United States might also be manifesting themselves in the United
      Kingdom through the introduction of market principles and the new "managerialism"
      into the National Health Service by the government and through the emergence of
      complementary medicine and the role of the "articulate" consumer. The authors
      explore these issues by focusing on how a sample of the "rank and file" of
      general practitioners perceive these potential challenges from "above and below."
      The evidence suggests that the social, economic, and clinical freedoms of general
      practitioners remain intact although these external influences appear to have
      changed the style of clinical practice, which is a source of concern and
      dissatisfaction to some general practitioners.

PMID- 7622316
TI  - Open the black box: paradoxes and lacunas in Swedish health care reforms.
AB  - The idea of using contracting-out as a means for improving public administration
      dates back to the 1850s, but was then found to be infeasible. The same idea has
      now become a major building-block in Sweden's health care reforms. Driven by a
      productivity-focused political discourse and the premises of neoclassical
      economics, these reforms ignore motivational structures among health care staff.
      The result may be a delegitimizing of the welfare state from within--either
      through the extinction of care rationality and its replacement by wage
      rationality, or, at worst, through the spread of a commercial spirit among health
      care staff and/or staff frustration at the unavoidable downward adjustments in
      remuneration rates. The author points to three strategic choices that arise when
      insights from a labor-process perspective are taken into consideration.

PMID- 7622317
TI  - They don't care: unemployed physicians in the Nordic countries.
AB  - Recent sociological research on the medical profession has been concerned with
      the profession's power and autonomy. So far, little research has focused on the
      total loss of the market value of a large number of physicians, that is, on the
      increasing rate of unemployment among physicians in some European countries. The
      author describes the extent of physician oversupply in the Nordic countries and
      examines the reasons for and implications of the growing unemployment among
      physicians.

PMID- 7622318
TI  - Health service regionalization in New Brunswick, Canada: a bold move.
AB  - New Brunswick moved swiftly in 1992 to regionalize hospital and physician
      services along with the reform and expansion of other health care services. The
      dissolution of 51 hospital and community health services center boards and the
      establishment of eight region hospital corporations to oversee services in the
      seven health regions set the tone for regionalization in the province. The plan
      provides the flexibility to meet specific regional needs. The initial
      regionalization of hospital services was followed by the determination of the
      appropriate number, mix, and distribution of physician resources for each region,
      also to be managed by the region hospital corporation. The provincial
      government's central role not only guides the regions, but also uses incentives
      and disincentives to ensure that regional goals are.met. While regionalization is
      not new and some components of the New Brunswick plan have been used elsewhere,
      the effort offers an integrated model for the regionalization of hospital and
      physician services, with the expansion of complementary services.

PMID- 7622321
TI  - Means, goals, and outcomes of a comprehensive occupational health program for
      telephone operators.
AB  - A means-goals analysis requires a plan with some degree of distinctness, which is
      worked out beforehand and specifies reasonably clear goals and intended means.
      This article draws its material from a broadly designed strategy for
      organizational change that meets these criteria. A service division of Swedish
      Telecom underwent a program of comprehensive organizational change; major efforts
      were made to improve the occupational health of 300 telephone operators in manual
      service operations. Over a full three-year period, a number of specific problems
      were to be resolved. An independent research team evaluated the implementation of
      the program prospectively. The team followed an evaluation model in which
      stringent distinction was made between: (1) action areas, (2) intended specific
      means, (3) intended immediate goals, and (4) the longer-term favorable effects of
      achieving these immediate goals. In addition, an attempt was made to interpret
      and understand the findings of the means-goals evaluation by paying systematic
      attention to the implementation process and factors that might permit an
      understanding of the final outcomes of the program. Compared with other efforts
      to improve telephone operators' work conditions as reported in the research
      literature, this strategy for the promotion of change is broad and ambitious.

PMID- 7622322
TI  - Comments on "Cancer Mortality near Oak Ridge, Tennessee".
AB  - A recent article by Joseph Mangano concluded that changes in cancer mortality
      near Oak Ridge (Anderson County) in Tennessee over a 40-year period (1950-1989)
      suggest an increase in cancer deaths linked to radiation contamination. These
      conclusions are not supported by available, representative data. In his analysis,
      Mangano selected for comparison two three-year periods (1950-1952 and 1987-1989)
      that are not representative of the entire 40 years. An analysis by decade of the
      42-year period from 1950 to 1991, using U.S. mortality rates from the National
      Center for Health Statistics and Tennessee mortality rates from the NCHS and the
      Tennessee Health Department, shows that the relation between expected and actual
      cancer deaths for the white population of Anderson County does not differ from
      that for the State of Tennessee. In addition, changes in methods of reporting
      death statistics during the 40-year period invalidate any attempt to compare
      current cause-specific mortality data (such as cancer deaths) with data from the
      1950s. Relevant comparisons that can be made for the period 1970-1991 again show
      that cancer deaths for whites in Anderson County have been statistically
      equivalent to the expected rates.

PMID- 7622319
TI  - Hospitalizations of children and access to primary care: a cross-national
      comparison.
AB  - In the United States, hospital admissions for conditions sensitive to primary
      care are related to socioeconomic characteristics. The authors compare the
      prevalence of avoidable hospital admissions and their relationship to socio
      economic and primary care characteristics in Spain and the United States. A case
      control analysis of the relationship between avoidable hospitalizations and
      socioeconomic characteristics (illiteracy, unemployment, income) and primary care
      characteristics (type of physician and facilities for primary care) of children's
      area of residence was conducted in Spain. Bivariate statistical tests and
      conditional logistic regression were used to test the strength of the association
      among the variables, and to calculate the probability of being admitted to
      hospital for treatment of an ambulatory care sensitive (ACS) condition. Neither
      socioeconomic nor primary care characteristics affected this probability, and the
      rate of admission for ACS conditions was lower in Spain than in the United
      States. The provision of universal financial access to care and the availability
      of a consistent and accountable primary care provider are associated with lower
      hospitalization rates for conditions that are preventable with good primary care.

PMID- 7622320
TI  - The effect of copayments and income on the utilization of medical care by
      subscribers to Japan's National Health Insurance System.
AB  - This study uses cross-sectional data from Japan's 47 prefectures covering
      subscribers to Japan's National Health Insurance system to analyze the effects of
      income and copayment levels on the utilization of medical care. Multivariate
      regression models were run for the years 1984 and 1989, with the utilization
      ratio (number of health insurance claims per 100 insurance subscribers) for
      total, inpatient, outpatient, and dental services as the dependent variable.
      Independent variables included copayment per patient day, deflated per capita
      income, population density, percentage of subscribers over age 65, number of beds
      and clinics per 1,000 persons, and number of doctors and dentists per 1,000
      persons. The data were then stratified according to per capita income and
      percentage of insurance subscribers over the age of 65 in each prefecture. The
      copayment amount exhibited a small, but significant negative effect on the
      utilization of all medical services. Utilization of outpatient care was most
      sensitive to the copayment rate. The per capita income stratification models
      revealed the greatest copayment effect on inpatient care for the lowest income
      group. The results of the age stratification models support popular notions about
      the use of hospitals by the elderly as substitutes for elderly care facilities.
      The effects of copayments and income vary not only among the type of medical care
      (inpatient, outpatient, and dental) but also among the income and age
      stratifications of groups in the National Health Insurance system.

PMID- 7622323
TI  - Risks associated with long-term homelessness among women: battery, rape, and HIV
      infection.
AB  - The purposes of this study were to determine the prevalence of battery, rape, and
      HIV risk practices in a sample of long-term homeless women and to explore
      correlates of HIV risk practices. Fifty-three women who had been homeless for at
      least three months in the last year were interviewed at day and night shelters.
      The women were demographically similar to other samples of homeless men and women
      and had similar rates of drug use. However, a higher proportion of homeless women
      were exposed to battery (91 percent), rape (56 percent), and mental distress, and
      they had a smaller support network (three people). Eighty-six percent had been
      battered prior to homelessness. A positive association was found between HIV risk
      practices and the use of certain drugs and having a protector. A higher level of
      assertiveness was associated with less HIV risk. The study demonstrated that
      homeless women are at very high risk of battery and rape. Being homeless may
      require life-styles that increase the risk of HIV infection and transmission.

PMID- 7622325
TI  - Steady-state content of glycolytic/tricarboxylic acid-cycle intermediates,
      adenine nucleotide pools and the cellular redox-status in the infective (L3)
      larvae of (homogonic) Strongyloides ratti.
AB  - Infective (L3) larvae of Strongyloides ratti (homogonic strain) were freeze
      clamped (-196 degrees C) and the steady-state content of the glycolytic, Krebs
      tricarboxylic acid (KTA)-cycle intermediates and adenine nucleotides analysed.
      Comparison of the mass-action ratios (MARs) of the glycolytic enzymes with their
      apparent equilibrium constants (K9eq) indicate that phosphoglucomutase,
      glucosephosphate isomerase, triosephosphate isomerase, phosphoglyceromutase and
      phosphopyruvate hydratase reactions were all at or near equilibrium, whilst
      hexokinase, phosphofructokinase and pyruvate kinase were displaced from
      equilibrium. The S. ratti aldolase and myokinase appear to be somewhat displaced
      from equilibrium and thus may have pseudoregulatory roles. The adenylate energy
      charge (AEC), ATP/ADP ratio and the available adenylate energy (AAE) indices were
      0.9 +/- 0.04, 8.76 +/- 1.5 and 397 +/- 43, respectively. The free
      [NAD+]/[NADH+H+] ratio of the cytoplasmic compartment of S. ratti L3 larvae
      calculated employing the steady-state content of the oxidised and reduced
      substrates of lactate dehydrogenase (E.C. 1.1.1.27) and the combined
      glyceraldehyde 3-phosphate dehydrogenase (E.C. 1.2.1.12)/3-phosphoglycerate
      kinase (E.C. 2.7.2.3) system were ca. 523 and 1200, respectively. The
      free[NAD+]/[NADH+H+] ratio in the mitochondrial compartment of S. ratti L3 larvae
      calculated using the malate dehydrogenase (E.C. 1.1.1.37) equilibrium was found
      to be 1962:1. The data is discussed with respect to the predominantly aerobic
      nature of the energy metabolism of the L3 larvae.

PMID- 7622324
TI  - Cryptosporidium and cryptosporidiosis in man and animals.

PMID- 7622326
TI  - Status of hepatic glutathione-S-transferase(s) during Plasmodium berghei
      infection and chloroquine treatment in Mastomys natalensis.
AB  - Plasmodium berghei infection in Mastomys natalensis impaired the hepatic
      mitochondrial, microsomal and cytosolic glutathione-S-transferase(s) activity
      with 1-chloro-2,4-dinitrobenzene as substrate. The enzyme activity was
      concomitantly decreased with rise in parasitaemia. The decreased enzyme activity
      due to infection was almost normalized with oral treatment of 16 mg (kg body wt)
      1 of chloroquine for 4 days.

PMID- 7622327
TI  - Properties of uracil phosphoribosyltransferase from Giardia intestinalis.
AB  - Incorporation of pyrimidine ribonucleotides in Giardia intestinalis occurs via
      uracil phosphoribosyltransferase (UPRTase). The enzyme was purified over 1000
      fold to apparent homogeneity from parasite extracts, using Fast Protein Liquid
      Chromatography, namely Mono Q anion exchange, Mono P chromatofocusing and
      Superose 12 chromatography. The specific activity of the purified enzyme was 3100
      nmol min-1 mg protein-1. The enzyme was found to be a dimer of mol. wt. 76,000.
      Kinetic analysis, including initial velocity and product inhibition studies,
      indicated that it obeyed a rapid-random equilibrium mechanism. GTP and dGTP
      caused a dramatic increase in the activity of the enzyme, though there was no
      effect on the Michaelis constants. All other nucleotides tested were without
      effect or were inhibitory. The effect of GTP is similar to that observed for
      UPRTase from E. coli but not from other eukaryotes.

PMID- 7622328
TI  - Differential diagnosis of lung nematode parasites from livestock by
      electrophoretic techniques.
AB  - The protein profile, determined by SDS-PAGE, from different geographical strains
      (Slovakia and Spain) of Dictyocaulus filaria and Protostrongylus rufescens
      parasitizing Capra hircus and Ovis aries has been assayed. This protein profile
      has also been comparatively determined in D. viviparus isolated from lungs of Bos
      taurus killed in Slovakia, by SDS-PAGE. Protein profiles of D. viviparus and both
      strains of D. filaria were very similar while in P. rufescens a quite different
      protein profile was found. Furthermore, the isoenzymatic pattern of Lactate
      Dehydrogenase (LDH) has been studied in two different geographical strains of D.
      filaria and P. rufescens and in D. viviparus by starch gel electrophoresis. From
      both strains of D. filaria and from both sexes, the isoenzymatic pattern of LDH
      was characterized by the presence of five isoenzymes, four anodical and one
      cathodical. In contrast, males and females of D. viviparus showed a different LDH
      isoenzymatic pattern; males presenting two isoenzymes with anodical and
      cathodical migration, respectively, and females showed only a single isoenzyme
      with anodical migration. Moreover, the electrophoretic mobility of the D.
      viviparus isoenzymes was different to that of D. filaria. Therefore, LDH has been
      designated as an important diagnostic tool to differentiate between species of
      genus Dictyocaulus. Finally, the LDH isoenzymatic pattern in P. rufescens
      (Slovakian and Spanish strain) was identical in both sexes appearing as a single
      band with cathodical migration.

PMID- 7622329
TI  - Intraspecific variation of isoenzymes in Taenia taeniaeformis.
AB  - The technique of isoenzyme electrophoresis was applied to Japanese wild
      populations of Taenia taeniaeformis (isolated from Norway rats) and three
      laboratory reared isolates (KRN isolated from a Malaysian Norway rat, BMM from a
      Belgian house mouse and ACR from a Japanese gray red-backed vole). The average
      heterozygosities of Japanese wild populations were fairly small and total genetic
      variability was 0.0499. The genetic make-up of T. taeniaeformis in Norway rats
      was rather uniform in the whole of Japan. In KRN isolate, each of all 10 loci
      examined possessed the allele which was predominant in Japanese wild populations.
      Similarly, each of 9 loci in BMM isolate possessed the same alleles, but one of 2
      alleles at HK locus was different from that in the others. T. taeniaeformis
      parasitizing house mice and rats were considered to be genetically closely
      related to each other. In ACR isolate, 7 out of 10 loci possessed different
      alleles from those in the other populations. It was considered that ACR isolate
      was genetically distant and its phylogenetic origin in Japan should be different
      from worms parasitizing Norway rats.

PMID- 7622330
TI  - Corneal virulence, cytopathic effect on human keratocytes and genetic
      characterization of Acanthamoeba.
AB  - Acanthamoeba keratitis is a sight-threatening complication of corneal trauma or
      contact lens wear. Although the majority of corneal isolates of Acanthamoeba
      belong to Group II in the Pussard-Pons classification based on cyst morphology,
      they have been placed in at least six species and their genetic relatedness is
      uncertain. The aim of this study was to determine the virulence of, and the
      relationship among, strains derived from the cornea, the nasal mucosa, and other
      environmental sources. To assess virulence, 10(4) trophozoites of each strain
      were incubated with monolayers of human corneal fibroblasts. By day 7, 12 of 29
      strains tested had induced significant cytopathic changes. In addition, inocula
      of 10(4) cysts or trophozoites with 10(6) Corynebacterium xerosis were injected
      into the corneas of Porton rats; 11 amoebic strains induced infection within 7
      days. The correlation between the virulence of trophozoites in vitro and in vivo
      was 86%. Using allozyme electrophoresis, 23 Acanthamoeba strains clustered into 5
      major phylogenic divisions. Three divisions contained one or more strains that
      were virulent in the rat cornea. Virulent Pussard-Pons Group II strains clustered
      tightly to a fixed allelic difference of 13.6%. The eight corneal isolates
      clustered to 33%, dividing into three lineages. Five avirulent nasal isolates
      were strongly differentiated from other Group II strains. The results were not in
      accord with species designations based primarily on morphological criteria. These
      data suggest that particular subsets of Acanthamoeba strains are virulent in the
      human cornea.

PMID- 7622331
TI  - Antigens identified by monoclonal antibodies in tissue sections of Boophilus
      microplus.
AB  - A panel of monoclonal antibodies (mAbs) raised against midgut antigens of
      Boophilus microplus were used to probe various stages and organs of the tick. One
      of the monoclonal antibodies in this panel (QU13) has previously been shown to
      recognize protective antigens. Of the 18 mAbs tested, all except two (QU5 and
      QU12) reacted with sections of adult midgut and Malpighian tubules using an
      avidin-biotin alkaline phosphatase method for immunostaining. MAbs QU1, QU2, QU3,
      QU4, QU12, QU13, and QU18 reacted specifically with the lumenal surfaces of type
      III acini of the salivary gland. These seven mAbs also stained the midgut in
      larval sections indicating that the antigens recognized were not stage specific.
      However, none of the seven mAbs tested recognised antigens in either the adult
      ovary or the developing egg. Antigens which were immunogold labelled by mAbs QU1,
      QU4, QU11, QU13, and QU15 in electron microscopy were located either on or near
      the surface of the microvilli of digestive cells from the midgut of the adult
      tick. We conclude that common antigens are present on the lumenal surfaces of the
      adult midgut, type III acini of the salivary gland, and the Malpighian tubules
      and that these antigens are also located in the larval gut.

PMID- 7622332
TI  - Immunolabelling of fish host molecules on the tegumental surface of Ligula
      intestinalis (Cestoda: Pseudophyllidea).
AB  - Immunoblotting, SDS-PAGE and western blotting procedures were used to demonstrate
      cross-reactivity of a polyclonal anti-carp IgM antibody with components of roach
      serum. The polyclonal antibody labelled 2 major bands in both immune and normal
      roach sera corresponding to molecular masses of approximately 90 and 65 kDa. One
      of these bands (65 kDa) was considered to be heavy chain of fish immunoglobulin
      whilst the identity of the other remains uncertain. This cross-reaction has been
      exploited in immunofluorescence and immunogold labelling studies to localize fish
      host molecules on the tegumental membrane of Ligula intestinalis freshly removed
      from roach fry. Immunogold studies revealed a low level of host molecules to be
      associated mainly with the microthrix spines of the tegument with less gold
      labelling being observed on the microthrix shafts.

PMID- 7622333
TI  - Strongyloides ratti: mitochondrial enzyme activities of the classical electron
      transport pathway in the infective (L3) larvae.
AB  - Submitochondrial particles prepared from S. ratti L3 larvae exhibited NADH
      oxidase (NOX), NADH-ferricyanide reductase (NFR), NADH-cytochrome-c-reductase
      (NCR), succinate-cytochrome-c-reductase (SCR), and cytochrome-aa3-oxidase
      activities of 2.1 +/- 0.3, 8.9 +/- 1.3, 0.6 +/- 0.1., 1.0 +/- 0.2 and 1.2 +/- 0.3
      nm min-1 mg protein-1 respectively, at 37 degrees C. The NCR and NOX activities
      were 39.3% and 23.5% of the NFR activity, suggesting the occurrence of a rate
      limiting step or bifurcation of the respiratory electron transport (RET) pathway
      on the oxygen-side of RET-Complex I. The NCR activity was 50% that of cytochrome
      aa3-oxidase activity which suggests partitioning of electron flow at the level of
      RET-Complex III and/or the quinone-function. Antimycin A and rotenone but not 2
      thenoyl trifluoroacetone (TTFA) inhibited NCR activity, the EC50 values were 3.6
      x 10(-6) M, 3.7 x 10(-7) M, respectively. SCR activity was inhibited by antimycin
      A (EC50 = 3.8 x 10(-6) M) and TTFA (EC50 = 2.8 x 10(-5) M) but not by rotenone.
      The results suggest that presence of classical and alternate RET-pathways in S.
      ratti L3 larvae.

PMID- 7622334
TI  - The effect of electron transport (ET) inhibitors and thiabendazole on the
      fumarate reductase (FR) and succinate dehydrogenase (SDH) of Strongyloides ratti
      infective (L3) larvae.
AB  - The fumarate reductase (FR) and succinate dehydrogenase (SDH) activities of
      isolated submitochondrial particles (SMPs) prepared from axenised L3 larvae of S.
      ratti were characterised with respect to their response to a selected range of
      inhibitors. Rotenone (a specific inhibitor of electron transport Complex I)
      inhibited the S. ratti FR (EC50 = 3.0 x 10(-7) M) but not SDH. This strongly
      suggests that the S. ratti FR is functionally linked with the S. ratti ET-Complex
      I. 2-Thenoyltrifluoroacetone (TTFA, an inhibitor of ET-Complex II) inhibited FR
      (EC50 = 2.6 x 10(-5) M) and SDH (EC50 = 2.8 x 10(-5) M) with similar
      effectiveness. Sodium malonate (substrate analogue of succinate) had a greater
      affinity for SDH (EC50 = 6.8 x 10(-4) M), than FR (EC50 = 1.9 x 10(-2) M). Sodium
      fumarate was ca. 8-fold more effective in inhibiting the S. ratti FR (EC50 = 6.0
      x 10(-4) M) than SDH (EC50 = 4.8 x 10(-3) M). The S. ratti FR was more sensitive
      to inhibition by thiabendazole (TBZ; EC50 = 4.6 x 10(-4) M) than SDH (EC50 > 1.0
      x 10(-3) M), suggesting that one of the sites-of-action of TBZ to be the FR of S.
      ratti mitochondria. More potent inhibitors of S. ratti FR, if developed, may
      prove to be effective chemotherapeutic agents in the management of human
      strongloidiasis.

PMID- 7622335
TI  - Further evidence for the long distance dispersal of taeniid eggs.
AB  - Autopsy of Soay Sheep on St. Kilda revealed the presence of cysticerci of Taenia
      hydatigena despite the absence of the definitive host on the island. Both the
      intensity of infection and the prevalence increased with age implying that the
      sheep did not acquire immunity to reinfection or superinfection. The sheep on
      average ingested approximately 2.4 eggs per annum. This is far below that
      expected if an infected dog had visited the island even on a single occasion. The
      data provide evidence that taeniid eggs are being transported against the
      prevailing wind by wildlife from at least the nearest inhabited land mass to St
      Kilda some 60 km distant.

PMID- 7622336
TI  - Beyond the mental hospital: crisis intervention and continuity of care in
      Trieste. A four year follow-up study in a community mental health centre.
AB  - A sample group of 39 new patients with acute and severe crises underwent a 4-year
      follow-up study at the community mental health center in Trieste (CMHC). The CMHC
      is a full-time service, open 24 hours a day and 7 days a week, and is fully
      integrated into a network of services which has completely replaced the
      preexisting mental hospital. Evaluation shows: 1) a generally good outcome of the
      initial crisis; 2) a low relapse rate; 3) a tendency towards favourable long-term
      outcomes. In terms of practice, voluntary and compulsory hospitalization were
      avoided in favor of short-term day and night support in the CMHC. There were no
      suicides, no crimes, no drop-outs. Social adjustment remained unchanged.
      Accessibility and continuity of care were favored by not separating special
      crisis services. Instead, crisis intervention was integrated into a comprehensive
      Mental Health Service offering a wide range of preventive and rehabilitative
      responses. The study demonstrates that the mental health services in Trieste are
      able to cope with acute crises without psychiatric hospitalization.

PMID- 7622337
TI  - Psychological effects of colliery closures.
AB  - A 'factory closure' type study was conducted by postal survey to assess the
      impact of the colliery closure programme on individuals. Two collieries were
      studied, one 'threatened' and one 'unthreatened'. Replies were received from 30%
      of potential subjects. Miners at the threatened colliery had higher mean GHQ
      scores and reported greater alcohol consumption and more recent contact with
      their general practitioners. This study suggests that threat of unemployment and
      actual unemployment has a significant effect on psychological morbidity,
      potentially harmful behaviour and use of general practitioners.

PMID- 7622338
TI  - Family support and other social factors precipitating suicidal ideation.
AB  - To examine the effects of family support and demographics on suicidal behavior,
      385 subjects completed a demographic questionnaire and a Suicidal Ideation
      Questionnaire (SIQ). Sixteen percent described themselves as "serious" ideators,
      while 59% were seen as ideators, numbers consistent with past suicide research.
      Multiple regression analyses revealed that the type of caregiver a person
      reported having while growing up accounted for a significant amount of the
      variance on ideator status. Serious ideators were more common among single parent
      households. Although many demographic variables were assessed, only the primary
      caregiver a person had as a child impacted their status as a suicidal ideator.
      This suggests that suicidal behaviors may occur due to a complex interaction
      between social factors and childhood care. The influence of living in a single
      parent home may contribute to whether or not a person considers suicide.

PMID- 7622339
TI  - Use of the Brief Symptom Inventory to assess psychological distress in three
      immigrant groups.
AB  - This paper examined the internal consistency reliability of two newly developed
      alternate language versions of the Brief Symptom Inventory (BSI) (This is not the
      Bradford Somatic Inventory, which is also known as the BSI) when used with Polish
      and Filipino immigrants and the original versions of the BSI and its parent
      instrument, the Symptom Checklist 90 (SCL-90) when used with Irish immigrants;
      and, the theoretical and criterion related validity of the Psychoticism subscale
      of the BSI for Polish, Filipino, and Irish immigrants. Internal consistency
      estimates and triangulation of individual BSI global and subscale scores with
      verbal self-reports and clinical assessments demonstrated that the BSI is a
      relatively reliable and valid cross-cultural measure of psychological distress.
      However, problems with the Psychoticism subscale occurred across all three
      immigrant groups, which suggested that this subscale should be interpreted with
      caution when used with immigrants.

PMID- 7622340
TI  - Physical status and dementia risk: a three-year prospective study in urban Japan.
AB  - A three-year prospective study of 3,180 non-dementia persons in Sendai City,
      Japan was conducted to examine the effects of physical status and diseases
      diagnosed on dementia incidence. This cohort had been made at the initial survey
      in 1988 and the evaluation for incident dementia was performed on 2,461
      respondents (77.4%) in a follow-up survey in 1991. Regarding physical status, the
      logistic regression including sex, age, health status, ambulatory activity and
      activities of daily living indicated that the poor health status and the
      limitation of ambulatory activity were significantly associated with an increased
      risk of dementia. The significant positive association with dementia was observed
      on stroke, respiratory disease and depression. This study identified the high
      risk population for dementia in the aspect of physical status.

PMID- 7622342
TI  - Biological psychiatry in Israel: approaching the challenge of maturity.

PMID- 7622341
TI  - Children of South Sea Island immigrants to Australia: factors associated with
      adjustment problems.
AB  - Social-delinquent problem youth of South Sea Island immigrant to Australia
      parents, were compared to non-problem youth from the same circumstances, on
      family, sociocultural, personality, and substance abuse variables. Interviews and
      testing were done by members of their own community. A consistent pattern of
      differences most pronounced for males was found between the two groups although
      not all reached statistical significance. The problem youth compared to the non
      problem youth tended to come from families somewhat lower in socioeconomic level,
      somewhat less traditional in culture, and notably more prone to discipline by
      physical punishment than by verbal reasoning. The problem youth had significantly
      lower self-esteem, significantly higher maladjustment test scores, and
      significantly greater use and problems with alcohol and drugs. They were more
      alienated and had less clearly established direction for their future.
      Recommendations for remediation are considered.

PMID- 7622344
TI  - Recent developments in PET scan imaging of neuroreceptors in schizophrenia.
AB  - Among the brain imaging techniques developed during the past two decades,
      positron emission tomography (PET) has the highest sensitivity allowing the
      analysis of specific neurotransmitter mechanisms in the living human brain. By
      using a combination of selective ligands labeled with positron emitting isotopes
      D1- and D2 dopamine, serotonin 5HT2, and benzodiazepine receptors were examined
      in schizophrenic patients (DSM-III-R) and healthy control subjects. With this
      technique receptor populations could be excellently visualized and quantified
      with regard to number and binding characteristics in several brain regions. The
      characteristics of the total D1 and D2 dopamine receptor populations in the
      caudate and putamen did not differ in young drug-naive schizophrenic patients and
      age-matched control subjects. Also for 5HT2 and benzodiazepine receptors no major
      alteration of receptor characteristics was observed in several neocortical and
      limbic brain regions. However, in schizophrenic patients treated with chemically
      different types of antipsychotic drugs major reductions of ligand binding was
      observed indicating specific induction of neuroreceptor occupancy. Thus, all
      chemically different types of antipsychotic drugs examined induced a substantial
      occupancy of D2 dopamine receptors. Clozapine in high doses induced a
      significantly lower degree of D2 dopamine receptor occupancy than the
      conventional drugs. Some but not all antipsychotics also induced a significant D1
      dopamine receptor occupancy. In spite of the fact that the selective D1
      antagonist SCH 39166 induced a substantial D1 occupancy, this drug did not
      exhibit an antipsychotic effect in schizophrenic patients. A very high degree of
      5HT2 occupancy in neocortical regions was observed after clinical treatment with
      antipsychotic drugs as clozapine, risperidone and thioridazine.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7622343
TI  - Follow-up and relapse analysis of an inositol study of depression.
AB  - A recent controlled double-blind study of 28 patients treated with 12 gm daily of
      inositol or placebo revealed significant antidepressant effect for this second
      messenger precursor. Patients were followed-up by interview and Hamilton
      Depression Scale 10-12 months after the end of the study. Half of the patients
      who had responded well to inositol relapsed rapidly after inositol
      discontinuation whereas none of those who responded to placebo relapsed rapidly
      after placebo cessation. Klein suggested that true drug responders to tricyclic
      antidepressants respond slowly and gradually whereas placebo responders improve
      early in an abrupt fashion. However, in the recent study both inositol and
      placebo responders improved at similar rates. Hamilton Depression Scale Scores 10
      12 months after completion of the study were not significantly different between
      those who had responded and those who had not responded to inositol or to
      placebo.

PMID- 7622345
TI  - Respiratory and other symptoms in panic disorder versus other anxiety disorders.
AB  - Respiratory abnormalities have been proposed as a central feature of panic
      disorder, but the literature is not unanimous. Symptoms of anxiety were
      quantitatively recorded with the Hamilton Rating Scale for Anxiety (HAM-A) in 72
      psychiatric out-patients in two anxiety disorders clinics in Israel; 44 patients
      had panic disorder with or without agoraphobia and 28 patients had other anxiety
      disorders. Panic patients had more cardiovascular symptoms, but not more
      respiratory symptoms, than other patients. The relative importance of respiratory
      symptoms in panic disorder is not yet settled.

PMID- 7622346
TI  - Serotonin and suicidality: the impact of fluoxetine administration. II: Acute
      neurobiological effects.
AB  - Despite the demonstrated anti-depressant efficacy of the selective serotonin
      reuptake inhibitors (SSRIs), increased suicidal ideation and/or agitation have
      been reported in a small proportion of individuals receiving fluoxetine or other
      SSRIs. Part II of this review examines fluoxetine's acute effects on serotonergic
      functioning. Although acute fluoxetine administration produces a short-term
      compensatory decrease in the firing of 5-HT neurons, the neurobiological data
      reviewed suggests that this decrease probably does not lead to an over
      compensatory net decrease in 5-HT functioning. The implications of fluoxetine's
      complex effects on the 5-HT systems are discussed with respect to clinical
      practices and future research.

PMID- 7622347
TI  - The moral and the healthy: identical, overlapping or orthogonal?
AB  - The pathogenic paradigm which underlies almost all current Western medical
      research and practice focuses on concrete diseases and is devoted, at least in
      theory, to the relief of suffering from these diseases. Clearly, the relief of
      suffering is a humane, moral pursuit. I have posed the salutogenic paradigm as a
      major challenge, urging the importance of research directed to the understanding
      of the mystery of and clinical work directed to the facilitation of movement
      toward the health end of a health ease/dis-ease continuum. I have proposed the
      Sense of Coherence (SOC) concept as a key answer to the salutogenic question. As
      this model is increasingly welcomed, I have become increasingly sensitive to the
      ethical dangers raised by it, or by any orientation, such as the WHO definition
      of health, which has salutogenic elements. This paper is devoted to examining
      these ethical problems. The first follows from the need to define the concept of
      health. The temptation is to confuse health well-being with other aspects of well
      being, reflecting the value judgments of the definer. Such confusion becomes
      dangerous when the definer holds power over others. The second problem, which has
      two coordinate parts, is even more serious. It arises out of the search for
      health-promoting factors. It pressures one to assume that a. what is functional,
      useful and positive for health is morally good; and b. what is morally good is
      functional for health. (And, of course, the converse assumptions about moral
      evils.)

PMID- 7622348
TI  - Fluoxetine induced weight loss: a pilot study in postpartum women.
AB  - Twelve women who developed an average postpartum weight gain of 18.3kgs (SD +/-
      6.09) entered an open trial, for three months, of fluoxetine 20 mg daily. The
      weight gain during their pregnancies was nearly twice that recommended by the
      treating gynecologists. Seventy-five percent success rate was achieved -8/12 were
      +/- 5% of their pre-pregnancy weights upon completion of the trial. Mean weight
      upon entering the trial was 82.25kgs (SD +/- 13.39), and at termination, 65.75kgs
      (SD +/- 8.59), P < 0.001. Anorexia and weight loss (more than 5% of body weight)
      have been reported in the literature in 9% and 13%, respectively, of depressed
      patients treated with fluoxetine. The use of this drug to promote weight loss is
      here reported in a selected population of women without signs or symptoms of
      depression, whose weight gain during pregnancy was excessive.

PMID- 7622349
TI  - Diagnosis of dementia by different specialties.
AB  - The present study was undertaken to describe, explore and compare the specific
      methods and services provided by physicians of different specialties (general
      practitioners, geriatricians, neurologists, psychiatrists and geriatric
      psychiatrists) in the evaluation process of patients with suspected dementia in
      Israel. A self-administered questionnaire--mailed to 203 physicians (response
      rate 37%)--included items covering medical and specialty training, numbers of
      patients examined, evaluation approaches, use of formal diagnostic criteria, use
      of mini-mental tests, use of dementia severity rating scales, use of psychiatric
      and behavioral rating scales, and the use of laboratory examinations. Results
      indicate that the majority of physicians in all specialties either provided
      history taking, physical and neurological examination, or referred for it
      elsewhere. Deficiencies were noted regarding the use of psychiatric examination
      by the nonpsychiatric specialties, and provision of ADL evaluation by all
      specialties (except geriatricians). All specialties made a minimal use of
      neuropsychological tests. DSM-3/DSM-3R criteria for dementia were widely used by
      all specialties (except general practitioners). MMSE was the most widely used
      brief cognitive screening test. However, only a minority of general practitioners
      and psychiatrists made use of it. Laboratory tests in dementia evaluation were
      widely used by most physicians, irrespective of specialty. Further research is
      needed in order to define in more specific terms the advantages contributed by
      each specialty separately and in collaboration to the diagnostic process of
      dementia.

PMID- 7622350
TI  - Responsibilities of men and women in ultra-orthodox life.

PMID- 7622351
TI  - The meaning of ultra-orthodoxy.

PMID- 7622352
TI  - Cell type-oriented differential modulatory actions of saikosaponin-d on growth
      responses and DNA fragmentation of lymphocytes triggered by receptor-mediated and
      receptor-bypassed pathways.
AB  - We examined the immunoregulatory action of saikosaponin-d (SSd), which was
      isolated from the root of Bupleurum talcatum L. and had a steroid-like structure,
      on murine thymocytes, and compared the action with that on spleen cells.
      Constitutive DNA synthesis or the growth response stimulated with anti-CD3mAb of
      thymocytes were down-regulated by 3 micrograms/ml SSd, whereas with spleen cells
      these were up-regulated by the same concentration of SSd. On the other hand, 3
      micrograms/ml of SSd greatly up-regulated the growth response and interleukin 2
      (IL-2)/interleukin 4 (IL-4) production induced through a receptor-bypassed
      pathway by calcium ionophore A23187 plus phorbol 12-myristate 13-acetate (PMA) in
      thymocytes, whereas it only slightly up-regulated them in spleen cells. Moreover,
      the same concentration of SSd inhibited DNA fragmentation in thymocytes induced
      by A23187 or PMA. These results suggest a unique cell type-dependent immuno
      modulatory action of SSd.

PMID- 7622354
TI  - Pharmacokinetics and catabolism of tumor necrosis factor-alpha in rat lungs.
AB  - The role of the lungs in the catabolism of tumor necrosis factor alpha (TNF
      alpha) either in normal rats, or in rats subjected to an acute cigarette smoking
      episode has been evaluated by using isolated and perfused lung preparations.
      After administration of TNF-alpha into the lung perfusion medium, there was no
      clearance of the cytokine in both control and smoker rat lungs and only 0.2 +/-
      0.1% of the administered dose was recovered in the bronchoalveolar lavage fluid.
      When TNF-alpha was instilled into the bronchoalveolar tree, concentrations of the
      cytokine in the perfusate increased progressively so that after 3 h up to 68.8 +/
      8% and 52.7 +/- 11.4% of the administered dose had been transferred from the
      bronchial lumen to the perfusion medium of either control or smoker rat lungs,
      respectively, the latter values being significantly lower (p < or = 0.05) than
      those obtained in control lungs. Moreover, total recoveries of TNF-alpha
      evaluated in smoker rat lungs (65.5 +/- 10.2%) were also significantly lower than
      those observed in control rat lungs (82.8 +/- 7.1%). In conclusion, it appears
      that transfer of TNF-alpha is almost exclusively unidirectional, from the
      alveolar space to the plasma pool with partial degradation during the
      transalveolar passage. These results may be useful when attempting to deliver TNF
      alpha by aerosol.

PMID- 7622353
TI  - Modulation of immune function and cytokine production by various levels of
      vitamin E supplementation during murine AIDS.
AB  - Female C57BL/6 mice were infected with LP-BM5 retrovirus, causing murine AIDS
      which is functionally similar to human AIDS. Dietary supplementation, with a 15-,
      150- and 450-fold increase of vitamin E in a liquid diet, significantly restored
      levels of interleukin-2 (IL) and interferon-gamma produced by splenocytes, which
      were suppressed by retrovirus infection. Retrovirus infection elevated levels of
      IL-6 and IL-10 produced by splenocytes, which were significantly normalized by
      all levels of vitamin E supplementation, respectively. Increased levels of IL-6
      and tumor necrosis factor-alpha, produced by splenocytes during progression to
      murine AIDS, were also significantly normalized by all levels of vitamin E
      supplementation. Vitamin E supplementation restored retrovirus-suppressed
      splenocyte proliferation and natural killer cell cytotoxicity. Vitamin E
      supplementation also alleviated the AIDS symptoms: splenomegaly and
      hypergammaglobulinemia. These data indicate that dietary vitamin E
      supplementation at extremely high levels was not immunotoxic, and can modulate
      cytokine release and normalize immune dysfunctions during progression to murine
      AIDS. It should favorably affect host resistance and thereby retard the
      development of AIDS.

PMID- 7622355
TI  - Neutrophil-independent myocardial dysfunction during an early stage of global
      ischemia and reperfusion of isolated hearts.
AB  - The effect of global ischemia and reperfusion on the expression of cytokine genes
      and cell adhesion molecules by myocardial tissues and neutrophils was studied by
      using the Langendorff model. Although cardiac function deteriorated after
      reperfusion of ischemic hearts, there was no evidence of inflammation and
      myocardial degeneration, which is in contrast to previous findings that
      neutrophil-mediated inflammation is a critical step in post-ischemic reperfusion
      injury in regional ischemia. Flow cytometry analysis demonstrated that the global
      ischemia and reperfusion did not affect the expression of adhesion molecules on
      neutrophils. We also examined the expression of various cytokines which are
      involved in inflammatory responses. Only interleukin 1 alpha was induced after
      the reperfusion of the ischemic hearts. These results suggest that neutrophils
      barely contribute to the myocardial dysfunction and IL-1 alpha may play a role in
      post-ischemic myocardial dysfunction during the early stage of reperfusion.

PMID- 7622356
TI  - Bacterial response to host signals: analysis and applications.

PMID- 7622357
TI  - Cellular signaling by receptor tyrosine kinases.

PMID- 7622358
TI  - Biogenesis of epithelial cell surface polarity.

PMID- 7622359
TI  - T cell tolerance.

PMID- 7622361
TI  - Protection and damage by antiviral immunity.

PMID- 7622360
TI  - Genetic and structural strategies for MHC function.

PMID- 7622362
TI  - Signals on endothelium for lymphocyte recirculation and leukocyte emigration: the
      area code paradigm.

PMID- 7622363
TI  - A methodology for evaluating the toxicity of radioactive waste and its
      application to the radioactive waste generated in Pennsylvania.
AB  - Communicating with the public on the risks of low-level radioactive waste
      disposal is difficult due to the lack of comparisons that are understandable to
      the public. This paper presents a methodology for analyzing the intrinsic
      toxicity of radionuclides in waste and comparing it to that for soil or other
      wastes that may contain naturally-occurring radionuclides. The intrinsic toxicity
      of each radionuclide is normalized by dividing its specific activity in the waste
      by an appropriate ingestion risk standard, such as the U.S. EPA proposed drinking
      water limits. To illustrate the usefulness of this method, it was used to analyze
      Pennsylvania's commercial low-level radioactive waste inventory. The results are
      presented along with an indication of the usefulness of this method for screening
      purposes to analyze and identify problematic constituents in various waste
      streams.

PMID- 7622364
TI  - Distribution and enrichment of radionuclides in the newly discovered high
      background area in Ullal on the southwest coast of India.
AB  - In order to understand the distribution of radionuclides in the newly discovered
      high background area in Ullal near Mangalore, soil and sand samples collected
      from different depths were analyzed for the concentration of primordial
      radionuclides by gamma spectrometry. The activity of 232Th and 238U in soil and
      sand was observed to be maximum in the 0-10 cm layer. The activity of primordial
      radionuclides was determined for the different size fractions of soil and sand to
      study the enrichment pattern. The highest activity was found in the 250-125 mu
      fraction in both soil and sand. The concentration of primordial radionuclides in
      riverine and marine sediments in the vicinity of the high background area was
      measured to understand the transportation of radionuclides in riverine and marine
      environments and to throw light on the formation of the new patches of monazite
      deposit. The results of these systematic investigations are discussed in this
      paper.

PMID- 7622365
TI  - A proposed blood circulation model for Reference Man.
AB  - As part of the revision of the Reference Man model of the International
      Commission on Radiological Protection (ICRP), we have reviewed and reanalyzed
      available data on blood flow and in previous publications have proposed reference
      values for total and regional blood volumes, total cardiac output, and the
      distribution of cardiac output. In this paper we unify these proposed features of
      the revised Reference Man within the framework of a dynamic blood circulation
      model and show how the model can be used to predict the distribution of decays of
      short-lived radionuclides after injection or absorption into blood. The total
      blood volume is partitioned into the blood contents of 24 separate organs or
      tissues, right heart chambers, left heart chambers, pulmonary circulation,
      arterial outflow to the systemic tissues (aorta and large arteries), and venous
      return from the systemic tissues (large veins). As a compromise between physical
      reality and computational simplicity, the circulation of blood is viewed as a
      system of first-order transfers between blood pools, but outflow from any given
      pool is delayed during the first pass of material through the circulation with
      the delay time depending on the mean transit time across the pool. The model can
      be used to predict the movement and gradual dispersal of a bolus of material in
      the circulation after intravascular injection. In contrast to the treatment of
      the circulation in ICRP Publication 53, Radiation Dose to Patients from
      Radiopharmaceuticals, the present model allows consideration of incomplete,
      tissue-dependent extraction of material during passage through the circulation
      and return of material from tissues to plasma.

PMID- 7622366
TI  - Percutaneous absorption of tritium-gas-contaminated pump oil.
AB  - One of the radiological problems encountered in tritium handling facilities is
      the hazards associated with tritium's ability to label and degrade organic
      materials. Experiments in which male hairless rats have been contaminated with
      tritium-gas-contaminated pump oil have demonstrated that tritium deposited on the
      skin provides an input of organically bound tritium and tritiated water in the
      body. The accumulation of organically bound tritium at the point of contact in
      the skin and in various tissues influenced tritium excretion in urine and feces.
      The retention of tritium in the body showed that tritium was mainly metabolized
      and assimilated as organically bound tritium. The distribution of tritiated water
      was rapid and uniform in the whole-body. Analyses of tritium excreted in animal
      urine and feces showed that a significant level of organically bound tritium was
      excreted shortly after exposure. The highest concentration of tritium activity
      was measured in the exposed area of the skin. An increased level of tritium
      accumulation in the liver and kidneys was seen. Dose calculations showed that the
      exposed skin had the highest dose, and the skin dose was primarily due to the
      retention of organically bound tritium at the point of contact. The
      interpretation of these data has indicated that the retention of short-term
      organically bound tritium in the skin may be a dominant factor for dosimetry
      purposes.

PMID- 7622367
TI  - Reduced integral solutions for gamma absorbed dose from Gaussian plume.
AB  - Exact two-dimensional and asymptotic one-dimensional integral solutions were
      obtained for the external dose rate value due to a Gaussian plume. The relative
      error of the asymptotic solution was found to be less than 5% for downwind
      distances of 1 to 300 mean free path lengths and for crosswind distances of 0 to
      40 mean free path lengths. A good agreement was observed with the results of
      plume dose rate calculations published earlier.

PMID- 7622368
TI  - 222Rn in water: a study of two sample collection methods, effects of mailing
      samples, and temporal variation of concentrations in North Carolina groundwater.
AB  - The U.S. Environmental Protection Agency has proposed a drinking water standard
      for 222Rn in public water supplies. When promulgated, operators of public water
      supplies will be required to determine water 222Rn concentrations. Most likely,
      water samples will be collected and mailed to laboratories for analyses.
      Additionally, it is probable that homeowners will test private well water in a
      similar manner by collecting water samples and mailing them to a laboratory for
      222Rn analyses. In anticipation of these actions, this study was conducted to
      evaluate two methods of water sample collection and to evaluate the potential
      losses of 222Rn from water samples mailed to a laboratory. Thirdly, temporal
      variations in 222Rn concentrations in several groundwater supplies in North
      Carolina were examined. Water supplies at four sites in eastern North Carolina
      and five sites in western North Carolina were sampled over a 7-mo period
      beginning in the fall of 1993 and continuing through the spring of 1994. Samples
      were analyzed using a liquid scintillation method. This study showed that a "slow
      flow" method is not only suitable for sample collection, but may be the
      preferable method for water sample collection since slow-flow collection resulted
      in less 222Rn loss than was observed during syringe collection, i.e., the water
      222Rn concentrations in samples collected by the slow-flow method were generally
      higher. Further, based on this study, mailing water samples to a laboratory for
      analysis should not have a substantial effect on the measured 222Rn
      concentrations. Consequently, water samples can be collected by the slow-flow
      method by water supply operators, as well as homeowners, and mailed to
      laboratories for 222Rn analyses with reasonable assurance that the samples have
      not suffered significant 222Rn loss. Temporal variations in water 222Rn
      concentrations were observed in this study. One factor complicating the study of
      temporal variations in 222Rn concentrations was the striking influence that
      inconstant water usage and inadequate well purging prior to sample collection had
      on 222Rn loss from the water.

PMID- 7622370
TI  - Thorium lung burdens of mineral sands workers.
AB  - Thorium lung burdens have been measured in workers in the dry separation plants
      operated by the mineral sands industry in Western Australia. The data have been
      compared with historical employment records of the worker's exposure to thorium
      bearing airborne dusts in order to assess the reliability of personal air
      sampling and with the predictions of the new Task Group lung model. The thoron
      exhaled in the breath of 62 workers was measured using a double filter tube. Six
      of the workers also underwent in-vivo gamma counting to determine their thorium
      lung burden. A thoron exhalation rate of 4.7% was obtained from a comparison of
      the two data sets. The estimated thorium lung burdens from the thoron-in-breath
      measurements had a geometric mean value of 10 Bq. The workers had a geometric
      mean employment period in the industry of 9.2 y and a geometric mean total
      inhaled alpha activity of 9,000 Bq, estimated from contemporary personal air
      sampling data and a retrospective assessment of previous workplace conditions.
      This exposure corresponds to a mean daily intake of 232Th of 0.45 Bq. Predictions
      from the new Task Group lung model indicate that, for the 45 workers with a
      thorium lung burden in excess of the minimum detectable level (6 Bq), the daily
      intake of 232Th is a factor of 1.6 higher than expected. This result suggests
      that previous intake of radioactive dust was higher than generally assumed for
      some workers. The application of the new Task Group lung models to the bioassay
      data results in an estimated mean annual committed effective dose for the workers
      of 8 mSv. Two workers (3%) were found to have been exposed for many years in
      excess of the 50 mSv y-1 annual limit for occupational exposure, while eight
      workers (13%) exceeded the ICRP's proposed new occupational standard of an
      average of 20 mSv y-1. All eight had been employed for more than 6 y and the
      majority of their exposure was attributed to early employment years, prior to
      extensive workplace improvements in dust control.

PMID- 7622369
TI  - Mitigation of indoor radon in an area with unusually high radon concentrations.
AB  - In an area of unusually high indoor radon concentrations of up to 270,000 Bq m-3,
      four houses were selected for mitigation of indoor radon. Methods used were
      basement sealing, soil depressurization, a mechanical intake and outlet
      ventilation system with heat exchanger in the basement, and a multilayer floor
      construction using a fan to suck radon from a layer between bottom slab and
      floor. Basement sealing proved unsuccessful, the radon concentration remained
      unchanged after the mitigation attempt. The most successful remedial measure was
      soil depressurization using two fans and loops of drainage tubes to withdraw
      radon from the region under the floor and outside the walls of the basement and
      from soil under the part of the house without a basement. This method reduced the
      basement radon level in winter by about a factor of 200, i.e., from 100,000 Bq m
      3 to 500 Bq m-3, and the ground-floor level by about a factor of 400. As regards
      the mechanical intake and outlet ventilation system with heat exchanger in the
      basement, it is essential to ensure that ventilation provides increased air
      pressure in the basement compared to outdoors. Unbalanced mechanical intake and
      outlet ventilation may decrease the air pressure indoors compared to outdoors,
      leading to increased radon concentrations. Optimization of this method reduced
      radon concentrations from 200,000 Bq m-3 to 2,000-3,000 Bq m-3 in winter. In one
      house with only a very small basement, a multilayer floor construction using a
      fan to suck radon from a layer between the bottom slab and floor was found to
      reduce radon concentrations on the ground floor from 25,000 Bq m-3 to about 1,700
      Bq m-3 in winter. The results show that even in areas with extremely high radon
      concentrations, effective mitigation of indoor radon can be accomplished if
      suitable techniques are used. The evaluation of the different mitigation methods
      shows good coincidence with the ICRP 65 report.

PMID- 7622371
TI  - A sensitivity study of the SCK.CEN BIOSPHERE model for performance assessment of
      near-surface repositories.
AB  - At SCK.CEN a model has been developed on behalf of NIRAS/ONDRAF for the
      performance assessment of near-surface repositories, consisting of several
      submodels. This article deals with the submodels BIOSPHERE, describing the
      transfer and accumulation of the radionuclides in the biosphere and DOSE,
      calculating effective individual doses to the critical group. An extensive
      literature review was performed in order to determine best-estimate values and
      uncertainty ranges (probability density functions) of biosphere parameter values,
      specific to conditions that may prevail at potential disposal sites in Belgium.
      In this paper the BIOSPHERE and DOSE models are described and default and site
      specific values (probability density functions where appropriate) of the
      parameters involved are indicated for the radionuclides 129I, 239Pu, and 94Nb. A
      combined uncertainty/sensitivity analysis based on the pdf of the site-specific
      parameter values has been carried out. Median values and 95% confidence intervals
      of the site-specific doses are indicated and most influential parameters to the
      uncertainty identified. Site-specific median dose values are also compared with
      generic doses.

PMID- 7622372
TI  - Significant digits: foundations, myths and utilization.
AB  - Scientific text books, journal articles, and all types of other sources of
      scientific information frequently give certain recommendations and/or make
      statements of presumed fact concerning the issue of significant digits in
      scientific computation. Most of these "well-known" facts concerning significance
      in computation are false. This article discusses the folklore of significant
      digits, debunks the common cliches, illustrates the actual behavior of
      computational significance in a typical scenario, and makes recommendations
      concerning these matters.

PMID- 7622373
TI  - Occupational exposure in pediatric cardiac catheterization.
AB  - Radiation doses to staff involved with pediatric cardiac catheterization were
      measured using thermoluminescent dosimeters in 18 procedures. The average doses
      to the lens and thyroid, and the effective dose per procedure to the main
      operating physicians was 88, 180, and 8 microSv, respectively; to assistant
      physicians, 23, 51, and 2 microSv; and to technicians, 23, 27, and 2 microSv. In
      some procedures, the dose to the technician's hand approached 1,500 microSv. The
      doses received by physicians were proportional to cineangiographic time but with
      no correlation with integrated currents. The number of procedures which may be
      performed in a year by individual staff members was estimated to be 430 and 2,780
      procedures for physicians and assistants, respectively. It was suggested that the
      front of the neck is an adequate position for the dosimeter to measure doses
      during pediatric catheterization.

PMID- 7622374
TI  - Estimates of thyroid equivalent dose in Lithuania following the Chernobyl
      accident.
AB  - The volatile radioiodine was detected in Lithuania in the very first days after
      the Chernobyl accident. The proportion of gaseous 131I species of airborne iodine
      identified during that period exceeded from 2 to 4 times the aerosol fraction.
      The radioiodine activity of milk consumed by inhabitants of Lithuania varied over
      a broad range. 131I activity in milk reached a peak on the fourth day after
      deposition and then decreased with an effective half-time ranging from 4.2 +/-
      0.6 d to 5.2 +/- 0.9 d. Thyroid examinations by dosimetric teams were not
      available in Lithuania for reasons beyond the control of experimenters. Because
      of this, thyroid equivalent doses were estimated using the modified ICRP three
      compartment cyclic model. These calculations applied Monte Carlo methods and
      consideration of regional iodine deficiency to generate frequency distributions
      of equivalent doses to the infant and adult thyroid gland in three areas of
      Lithuania with different contamination levels.

PMID- 7622375
TI  - Fission fragment relative biological effectiveness for liver tumor induction.
AB  - The risk coefficients for liver tumors as derived from 60 beagles with body
      burdens of 249Cf or 252Cf were used to determine the relative biological
      effectiveness of fission fragments relative to alpha particles. For liver
      malignancies the relative biological effectiveness was calculated to be about 2
      +/- 3. The estimate based on the combined benign and malignant liver tumors was
      about 7, with a proportionately larger standard deviation of about +/- 14.
      Although the confidence intervals were wide, it is possible that the relative
      biological effectiveness of fission fragments relative to alpha particles, using
      liver neoplasia as the endpoint, is greater than 1.0 as compared to a value only
      slightly above zero when bone cancer was the lesion of interest.

PMID- 7622376
TI  - Soft tissue tumors among beagles injected with 90Sr, 228Ra, OR 228Th.
AB  - The occurrence of soft-tissue tumors in beagles given 90Sr (88 dogs), 228Ra (76
      dogs), or 228Th (81 dogs) as young adults and followed throughout their lifespans
      was compared with that of 133 control beagles given no radioactivity. For animals
      injected with 228Ra, tumors of the eye were more prominent (p < 0.05) than in the
      controls, and soft-tissue tumors of cavities in the head (excluding the brain,
      mouth, and eye) were more prominent in dogs given 90Sr than in the controls (p <
      0.05). There was some indication that eye tumors in animals given about 0.56 kBq
      228Th kg-1 were associated with their radionuclide exposure. For tumors at a few
      other locations, the relative occurrence was greater (p < 0.05) in the controls.
      These included malignant tumors of the testis and malignant plus benign tumors of
      the mammae and vagina in 228Th dogs; both malignant and malignant plus benign
      tumors of the mouth and testis, and malignant plus benign tumors of the mammae
      and vagina in 228Ra dogs; and malignant plus benign tumors of the mammae in 90Sr
      dogs (p > 0.05 by Odds Ratio Chi Square analysis but p < 0.05 by Fisher's Exact
      Test). Differences in relative occurrence between radioactive dogs and controls
      of all other tumor types that appeared in any of the animals (notably
      lymphosarcoma, lymph node tumors, leukemia, mast cell tumors, liver tumors, etc.)
      were not statistically significant (p > 0.05). Intercurrent mortality, mainly
      from bone cancer, was higher in the radioactive dogs than in the controls. Mean
      survival was reduced in the dogs given 90Sr, 228Ra, or 228Th (13.17 +/- 2.64 y in
      controls, 10.95 +/- 4.06 y in 90Sr dogs, 9.07 +/- 3.61 y in 228Ra dogs, and 9.20
      +/- 4.15 y in 228Th dogs). Attenuated lifespans could account, at least in part,
      for the relative paucity of soft-tissue tumors not induced by radiation among the
      groups of dogs given radioactivity and occurring near the end of life for control
      animals.

PMID- 7622377
TI  - Simple physical, chemical, and biological safety assessments as part of a routine
      institutional radiation safety survey program.
AB  - To assist in providing comprehensive surveillance for potential health and safety
      hazards, simple assessments of physical, chemical, and biological safety concerns
      were incorporated into traditional radiation safety facility surveys for a
      biomedical research and clinical care facility for a 1-y period. Customized
      training was provided to radiation safety staff members concerning each of the
      hazard areas identified and a brief checklist was developed. During the 1-y
      period 802 laboratory and clinic surveys were performed, and of the 372 safety
      issues noted by the staff, approximately 55% were identified as not related to
      traditional health physics surveillance activities. The utilization of these
      simple safety audit tools as part of a routine radiation safety surveillance
      program can serve as a cost effective way to assist in maintaining a teaching,
      research, and clinical environment that is free from a variety of recognized
      hazards.

PMID- 7622378
TI  - ALARA Overview System at Crystal River Unit 3 Nuclear Station.
AB  - During the Spring of 1994 the Health Physics Department at Florida Power Company
      used video and audio equipment to support remote health physics coverage for
      their Crystal River Unit 3 refueling outage (Refuel 9). The system consisted of
      eight cameras with audio interface linked to a control center located in a low
      dose area. The system allowed health physics personnel to monitor steam generator
      and refueling activities with minimum exposure in high-dose areas, cutting by
      half the dose from the previous outage. B&W Nuclear Technologies provided
      complete setup, maintenance and tear-down, as well as assuming responsibilities
      for contaminated video and audio equipment.

PMID- 7622379
TI  - Prediction of inhaled thorium.

PMID- 7622381
TI  - Risk vs. safety analysis.

PMID- 7622380
TI  - Correction in the screen losses definition.

PMID- 7622382
TI  - Comment on Table 3 of ICRP Publication 60.

PMID- 7622383
TI  - More about equivalent dose and dose equivalent.

PMID- 7622384
TI  - WHO defined health promotion as "the process of enabling people to increase
      control over and improve their health".

PMID- 7622385
TI  - New Zealand's SIDS prevention program and reduction in infant mortality.
AB  - New Zealand has suffered a very high mortality rate from sudden infant death
      syndrome (SIDS), also known as "crib death" or "cot death." This prompted the
      development of the New Zealand Cot Death Study, a case-controlled epidemiological
      study. The preliminary findings of this study identified three risk behaviors
      potentially amenable to modification: prone sleeping position of the infant,
      maternal smoking, and not breastfeeding. These findings were discussed with the
      major stakeholders of child health. The Department of Health coordinated the
      development of a health education SIDS prevention program. Since the Help Prevent
      Cot Death Programme was launched in February 1991, the rate of total infant
      deaths, which was 10.1/1,000 live births in 1987, fell to 7.6/1,000 live births
      in 1991. The SIDS rate fell from 4.2/1,000 in 1987 to 2.5/1,000 in 1991. It is
      suggested that the described health education program had a significant influence
      on this improvement in infant survival.

PMID- 7622386
TI  - Health interventions for African American and Latino youth: the potential role of
      mass media.
AB  - Children in Latino and African American families are far more likely to live in
      urban, high-poverty settings that greatly increase risks to healthy development.
      During adolescence, these settings are particularly hazardous for their role in
      the social transmission of risk behavior. Community-wide health promotion using
      local mass media can counteract these influences by reaching preadolescents and
      adolescents, their parents, and other adults in urban communities with safe
      behavior messages. These messages can be designed to make safer behavior more
      acceptable and normative in the community, to increase awareness of community
      resources for adolescents, and to reverse the stereotyping and disregard that
      characterize media content about impoverished communities. Evidence is reviewed
      that, despite their poverty status, African American and Latino communities have
      considerable social resources to which community-wide health promotion can
      appeal, including strong family bonds, religious attachment, and concern about
      the community. The influence of these resources is exemplified by relatively low
      rates of adolescent drug use. Health promotion conducted regularly through local
      mass media could be an effective strategy to improve the health of adolescents in
      urban communities.

PMID- 7622387
TI  - Goal setting as a strategy for health behavior change.
AB  - This article discusses the beneficial effects of setting goals in health behavior
      change and maintenance interventions. Goal setting theory predicts that, under
      certain conditions, setting specific difficult goals leads to higher performance
      when compared with no goals or vague, nonquantitative goals, such as "do your
      best." In contrast to the graduated, easy goals often set in health behavior
      change programs, goal setting theory asserts a positive linear relationship
      between degree of goal difficulty and level of performance. Research on goal
      setting has typically been conducted in organizational and laboratory settings.
      Although goal setting procedures are used in many health behavior change
      programs, they rarely have been the focus of systematic research. Therefore, many
      research questions still need to be answered regarding goal setting in the
      context of health behavior change. Finally, initial recommendations for the
      successful integration of goal setting theory in health behavior change programs
      are offered.

PMID- 7622388
TI  - Balanced incomplete block design: description, case study, and implications for
      practice.
AB  - This article discusses the use of balanced incomplete block design for process
      evaluation and presents a case study of its use. This technique produces a
      weighted ranking of program elements, showing the relative importance of each
      element and allowing comparison of process and content elements. The article
      presents a case study in which the technique was used to evaluate the Chronic
      Disease Self-Management Program. Participants and lay course leaders were asked
      to rank 13 course elements for their helpfulness. The most valued element,
      sharing or unstructured interactions among participants, was not an explicitly
      planned part of the intervention. Some of the elements least valued (nutrition,
      use of community resources, and medication use) are elements most emphasized by
      the health care system and by patient education. We found that balanced
      incomplete block design was easy to administer and tally. The results could be
      readily applied to program redesign and to needs assessment.

PMID- 7622389
TI  - Person and environment in HIV risk behavior change between adolescence and young
      adulthood.
AB  - This article explores how personal and environmental variables influence change
      in human immunodeficiency virus (HIV)-related risk behaviors between adolescence
      and young adulthood. Repeated interviews with 602 youths from 10 cities across
      the United States provide the data. These interviews first occurred in 1984-1985
      and 1985-1986 when the youths were adolescents and were repeated again in 1989
      1990 and 1991-1992 when they were all young adults. A longitudinal multivariate
      analysis shows that 31% of the variance in HIV risk behaviors by inner-city young
      adults is predicted by a combination of adolescent risk behaviors, personal
      variables (suicidality, substance misuse, antisocial behavior), environmental
      variables (history of child abuse, poor relations with parents, stressful events,
      peer misbehavior, number of AIDS prevention messages), and interactions between
      variables (number of neighborhood murders with child abuse, number of
      neighborhood murders with substance misuse, and unemployment rates with
      antisocial behavior).

PMID- 7622390
TI  - Diffusion of AIDS curricula among Dutch secondary school teachers.
AB  - This study reports data from a sample of 698 Dutch secondary school teachers
      intending to provide classroom AIDS education. The study addresses determinants
      of awareness knowledge about and adoption of four nationally disseminated AIDS
      curricula. The results indicated that knowledge acquisition was largely dependent
      on diffusion networks within schools. Transition from awareness knowledge to
      adoption appeared to be mediated by perceived instrumentality, subjective norms,
      perceived colleague behavior, and teachers' sexual morality. Preferences for
      using one curriculum rather than another were related to the same variables,
      although financial costs became slightly more important. It is concluded that
      effective dissemination strategies should combine (1) development of validated
      materials with clear instruction for implementation, (2) focused mass media
      communication, (3) close collaboration of curriculum designers, linking agents,
      and teachers, and (4) access to in-person assistance.

PMID- 7622391
TI  - Developmental status, gender, age, and self-reported decision-making influences
      on students' risky and preventive health behaviors.
AB  - This study used decision-making theory to analyze the developmental changes
      associated with children's and adolescents' health behavior. High school and
      elementary school children completed surveys concerning (1) the extent to which
      they engage in a variety of preventive and risky health behaviors, and (2)
      influence sources used in decision making concerning the enactment of these
      behaviors. Multiple regression analysis revealed that the sources of influence
      children and adolescents report considering in making health-related decisions
      change developmentally and as a function of gender. Moreover, within and across
      age, children's sources of influence with respect to health decision making are
      dependent on the health domains being considered. The findings are discussed in
      relation to decision-making theory and the implications for the content and
      timing of health education initiatives for adolescents.

PMID- 7622392
TI  - A review of impedance cardiography.
AB  - OBJECTIVE: To review the reliability and validity estimates of impedance
      cardiography to assess its empirical precision and clinical usefulness. DATA
      SOURCE: Empirical and theoretical literature mainly within the last 10 years.
      DATA SYNTHESIS: Descriptive statistics used to summarize the accuracy and use of
      impedance cardiography to estimate stroke volume. CONCLUSIONS: Estimation of
      cardiac output is presently a core component of optimizing cardiac function in
      many patient populations. Impedance cardiography, which initially used a formula
      developed by Kubicek et al. and recently a formula developed by Sramek and
      Bernstein, remains controversial with regard to its accuracy and use in research
      and clinical practice.

PMID- 7622394
TI  - Coronary risk factor status after percutaneous transluminal coronary angioplasty.
AB  - OBJECTIVE: To determine whether patients modify their risk factors after
      undergoing percutaneous transluminal coronary angioplasty (PTCA). DESIGN: One
      group, pretest-posttest. Pretest data were collected on the day before PTCA, and
      posttest data were collected at a mean follow-up of 11 months after PTCA. Data
      were collected from medical records and by patient self-report. SETTING:
      University-affiliated, metropolitan public and private hospitals. PATIENTS: Two
      hundred nine patients undergoing PTCA. OUTCOME MEASURES: Patients' smoking and
      exercise habits were assessed by self-report. Serum cholesterol level and body
      mass index were determined from entries in medical charts. RESULTS: All measured
      risk factors, with the exception of smoking, underwent favorable change (p <
      0.001) after PTCA. The number of current smokers, however, increased
      significantly (p < 0.001), as did the number of cigarettes these patients smoked
      per day (p < 0.05). CONCLUSION: Evaluation of the effect of intervention
      strategies on reducing patients' smoking behavior after PTCA is required.

PMID- 7622393
TI  - Evaluation of impedance cardiography: comparison of NCCOM3-R7 with Fick and
      thermodilution methods.
AB  - OBJECTIVE: To assess the degree of error of the BoMed NCCOM3 model revision seven
      (R7) impedance cardiograph in determining stroke volume and estimated cardiac
      output. DESIGN: Three-group, within-subject, repeated measures design. SAMPLE:
      Group 1: patients (n = 17) with heart disease undergoing an elective coronary
      angiogram; group 2: patients (n = 28) after elective heart surgery; and group 3:
      healthy volunteers (n = 28). MEASUREMENT: Cardiac output was determined by the
      BoMed NCCOM3-R7 impedance cardiograph, Fick principle, and thermodilution method.
      The NCCOM3-R7 was compared with the direct Fick and thermodilution methods in
      groups 1 and 2, respectively, to estimate validity coefficients. In group 3,
      repeated measures were obtained with the NCCOM3-R7 to calculate reliability
      coefficients. RESULTS: The NCCOM3-R7 underestimated Fick measurements by 1.050 +/
      1.529 L/min at rest and 1.505 +/- 2.214 L/min during exercise. Correlation
      coefficients of 0.684 at rest (p = 0.001) and 0.219 during exercise (p = 0.248)
      were obtained. The NCCOM3-R7 underestimated thermodilution values by 0.425 +/-
      1.325 L/min in subjects initially after heart surgery and 0.358 +/- 1.235 L/min 2
      to 4 hours later. Correlation coefficients of 0.547 (p = 0.002) and 0.505 (p =
      0.004) were obtained for the two time periods, respectively. A reliability
      coefficient of 0.837 was calculated with healthy subjects. CONCLUSION: The NCCOM3
      R7 has a clinically unacceptable level of error for evaluating cardiac
      performance in patients with heart disease.

PMID- 7622395
TI  - Cardiac catheterization: the patients' perspective.
AB  - OBJECTIVE: To identify the patients' experience of cardiac catheterization.
      DESIGN: Descriptive, qualitative, phenomenologic. SETTING: Large southeastern
      teaching hospital with an active cardiac catheterization laboratory and research
      center. PATIENTS: Ten men, between 44 and 73 years of age, who had undergone
      their first cardiac catheterization. RESULTS: The participants described feelings
      of loss of control of physical and personal self; an increased fear of the
      unknown during the test and especially of outcomes that might affect their
      future; a focus on time and its relationship to complication; a need not to be
      alone and not to be isolated after the test; and an awareness of spiritual belief
      in the good of others, trusting in their competencies. CONCLUSIONS: This study
      suggests the need for more attention to the psychologic aspects of the test,
      especially to the outcomes, negative as well as positive, and how they may affect
      the patient.

PMID- 7622396
TI  - Usefulness of measures of Svo2, Spo2, vital signs, and derived dual oximetry
      parameters as indicators of arterial blood gas variables during weaning of
      cardiac surgery patients from mechanical ventilation.
AB  - OBJECTIVES: To determine whether combined use of the parameters of mixed venous
      oxygen saturation, arterial oxygen saturation obtained by pulse oximetry (Spo2),
      and vital signs correlated with arterial blood gas variables (ABGs) better than
      each individual variable during weaning of postoperative cardiac surgery patients
      from mechanical ventilation; and to evaluate the relationship of derived
      parameters: oxygen extraction index and ventilation/perfusion index (VQI), and
      ABGs. DESIGN: Secondary analysis of previous correlational study. SETTING: The
      cardiac care unit in a large medical center in central Florida. PATIENTS: Thirty
      postoperative coronary artery bypass graft patients being weaned from mechanical
      ventilation. METHODS: After a change in ventilator settings during systematic
      weaning towards extubation, measurements of variables were taken during a 30
      minute period. At 30 minutes, an ABG was drawn for comparison. Data were
      collected after two ventilator changes. A total of 57 data sets were used for
      analysis. RESULTS: By use of multiple regression analyses, statistically
      significant (p < 0.01) independent variables predicting pH and partial pressure
      of carbon dioxide were Spo2 and respiratory rate. The independent variable
      contributing to the model versus partial pressure of oxygen was Spo2. The oxygen
      extraction index did not correlate with ABGs; however, the VQI correlated
      significantly with all ABG variables except bicarbonate. CONCLUSIONS: The use of
      multiple parameters was no more useful in predicting ABGs than individual
      variables of Spo2 and respiratory rate. The derived VQI parameter correlated with
      ABGs. The use of VQI in conjunction with Spo2 and respiratory rate may assist in
      patient monitoring during weaning and reduce the number of ABGs needed.

PMID- 7622397
TI  - Designer genes and critical care nursing: the future is now.
AB  - Discoveries about the human genetic code and innovations to manipulate genes are
      rapidly advancing. Laboratory strategies used for recombinant deoxyribonucleic
      acid techniques have revolutionized medication production and have led to
      experimental protocols for gene therapy. The implications for critical care
      nursing practice are profound. To keep pace with new discoveries, critical care
      nurses now need to consider the impact of advances in genetic engineering on
      their practice. Nurses assisting with gene therapy protocols will need to not
      only update their knowledge of genetics but also learn the fundamentals of
      recombinant technology. Administration of genetically engineered medications
      almost certainly will lead to new clusters of side effects and new routes for
      delivery. A multitude of ethical considerations such as biosafety and patient
      selection raises a realm of clinical practice implications. To provide the care
      that critically ill patients require, practitioners will need to update their
      knowledge constantly about the rapidly changing discipline of genetics and how
      advances in genetics relate to nursing and medical practice.

PMID- 7622398
TI  - Assessing agreement between clinical measurement methods.
AB  - Nursing practice and research often require the use of one measurement method in
      place of another, creating the need to know how well one clinical measurement
      method approximates another. The usual statistical analyses for assessing
      agreement between measurement methods are the correlation coefficient and the
      paired t test. This article suggests that these statistical methods do not
      address the question of agreement. It proposes the limits of agreement as a more
      informative analysis when a researcher is interested in replacing one measurement
      method with another. The application of limits of agreement analysis to assess
      repeatability of one measurement method is also introduced.

PMID- 7622399
TI  - Using the journal club as a component of the research utilization process.
AB  - Although journal clubs are recommended for research utilization, the various ways
      in which journal clubs are conducted do not always lead to research utilization.
      Major institutional changes in practice must be preceded by a comprehensive
      literature search and a complete review. An example is provided of how a series
      of journal clubs using the comprehensive search approach led to research
      utilization.

PMID- 7622400
TI  - Artificial neural network predictions of lengths of stay on a post-coronary care
      unit.
AB  - OBJECTIVE: To create and validate a model that predicts length of hospital unit
      stay. DESIGN: Ex post facto. Seventy-four independent admission variables in 15
      general categories were utilized to predict possible stays of 1 to 20 days.
      SETTING: Laboratory. SAMPLE: Records of patients discharged from a post-coronary
      care unit in early 1993. RESULTS: An artificial neural network was trained on 629
      records and tested on an additional 127 records of patients. The absolute
      disparity between the actual lengths of stays in the test records and the
      predictions of the network averaged 1.4 days per record, and the actual length of
      stay was predicted within 1 day 72% of the time. CONCLUSIONS: The artificial
      neural network demonstrated the capacity to utilize common patient admission
      characteristics to predict lengths of stay. This technology shows promise in
      aiding timely initiation of treatment and effective resource planning and cost
      control.

PMID- 7622401
TI  - Respiratory syncytial virus pneumonia in a heart transplant recipient presenting
      as fever of unknown origin diagnosed by gallium scan.

PMID- 7622402
TI  - Accuracy of infrared ear thermometry and traditional temperature methods in young
      children.

PMID- 7622403
TI  - Changes of motor evoked potentials in global and focal ischemic models of cats.
AB  - In order to evaluate the significance of motor evoked potentials (MEPs) in
      central nervous system monitoring, the authors conducted two sets of experiments
      using feline ischemic models. Twenty-three adult mongrel cats were divided into
      two groups: global (n = 9) and focal ischemic (n = 14) groups. In the case of
      global ischemia, which was induced by hypovolemic hypotension due to blood
      letting, deterioration of the D wave began when the mean arterial blood pressure
      (MABP) approached 45 mmHg, and regional cerebral blood flow (rCBF) dropped to 40%
      of control. Complete disappearance of the D wave was observed below 30 mmHg in
      MABP and 20% of control in rCBF. In the case of focal ischemia, which was induced
      by transorbital occlusion of the middle cerebral artery, the percentages of rCBF
      at which the D wave disappeared ranged from 9 to 20%. Changes in the amplitude of
      the D wave--an increase and following decrease--preceded the prolongation of its
      latency. In contrast with the D wave I waves were too easily affected by
      ischemia. Moreover, rCBF at the point of disappearance of the I wave varied
      greatly. In conclusion, the D wave is stable in mild ischemia and is a reliable
      indicator of critically profound ischemia (%rCBF < 40%). Monitoring the D wave of
      MEPs seems to be a useful method for avoiding the deterioration of motor function
      by ischemic insult.

PMID- 7622404
TI  - Cytophagic histiocytic panniculitis in systemic lupus erythematosus.
AB  - This paper presents a case of cytophagic histiocytic panniculitis in a Japanese
      woman, who had systemic lupus erythematosus complicated with Hashimoto's
      thyroiditis and lupus nephritis from the age of 12. The patient had painful
      multiple purplish subcutaneous nodules on the face, trunk and extremities, high
      fever and liver dysfunction without coagulopathy. The histological features of
      the skin nodules were extensive histiocyte and/or macrophage infiltration often
      with leuko- and/or erythrophagocytosis in the subcutaneous fat tissue.

PMID- 7622405
TI  - A case of isolated acute DeBakey II redissection occurring in a postoperative
      survivor who underwent an arch replacement for acute DeBakey IIIb dissection.
AB  - A case of isolated acute DeBakey II redissection which occurred in a
      postoperative survivor who underwent an arch replacement for acute DeBakey IIIb
      dissection is reported. The operative findings revealed that there was an intimal
      tear above the left coronary cusp, that there was a false lumen in the native
      ascending aorta, and that a residual false lumen caused by the initial operation
      had not been detected. Redissection caused mainly by the operative procedure,
      such as the failure to include the site of the intimal tear in the original
      repair and the formation of a new dissection as a result of anastomotic failure,
      is frequently seen. However, isolated redissection is a rare condition. In this
      paper we discuss classification, diagnosis and treatment of redissection.

PMID- 7622406
TI  - A case of gas-containing liver abscess associated with emphysematous change in
      the gallbladder.
AB  - We describe a 77-year-old man with diabetes mellitus who developed a large gas
      containing pyogenic liver abscess after admission. Mild elevation of serum
      biliary enzyme levels suggested probable biliary trouble on admission.
      Ultrasonography and computed tomography showed a large abscess of the liver with
      gas formation and the presence of gas within the lumina of the gallbladder and
      biliary tract when the patient had fever, leukocytosis and evidence of hepato
      renal dysfunction. These findings suggest that the large liver abscess may have
      developed as a result of emphysematous cholecystitis.

PMID- 7622407
TI  - Modelling the acquisition of goal-directed behaviors by populations of neurons.
AB  - Recent neurophysiological studies have revealed the patterns of neuronal activity
      during the acquisition of goal-directed behaviors, both in single cells, and in
      large populations of neurons. We propose a model which helps three sets of
      experimental results in the monkey to be understood: (1) activity of single cells
      vary greatly and only population activities are causally related to behavior. The
      model shows how a population of stochastic neurons, whose behaviors vary widely,
      can learn a skilled conditioned movement with only local activity-dependent
      synaptic changes. (2) typical changes in neuronal activity occur when the rules
      governing the behavior are changed, i.e. when the relationship between cues and
      actions to reach a goal changes over time. There are two types of neuronal
      patterns during changes in reward contingency: a monotonic increasing pattern and
      a non-monotonic pattern which follows the change in the way the reward is
      obtained. Units in the model display these two types of change, which correspond
      to synaptic modifications related to the encoding of the behavioral significance
      of sensory and motor events. (3) These two patterns of neuronal activity define
      two populations whose anatomical distributions in the frontal lobe overlap with a
      gradient organized in the rostro-caudal direction. The model consists of two
      artificial neural networks, defined by the same set of equations, but which
      differ in the values of two parameters (P and Q). P defines the adaptive
      properties of processing units and Q describes the coding of information. The
      model suggests that a balance in the relative strengths of these parameters
      distributed along a rostro-caudal gradient can explain the distribution of
      neuronal types in the frontal lobe of the monkey.

PMID- 7622408
TI  - The neurological development of prehension: a developmental neurologist's view.
AB  - From the developmental neurological point of view prehension is an important
      function as it involves the total sensorimotor nervous system. In order to make
      efficient performance possible both postural activity and motility of arms and
      hands must be coordinated, implying an intricate interplay between tonic and
      phasic activities. The analysis of the development of the different contributors
      suggests that they are based on independently developing brain mechanisms. This
      independency guarantees the variability which is required for adequately adaptive
      and purposeful functioning. A lack of this ability to vary, i.e. monotonous and
      stereotyped function resulting from deficient or deficiently coupled brain
      mechanisms leads to maladaptive and impaired motor function. Identification of
      the dysfunctioning brain mechanisms may inform treatment strategies.

PMID- 7622410
TI  - Developmental aspects of bereitschaftspotential in children during goal-directed
      behaviour.

PMID- 7622409
TI  - Variability and the development of skilled actions.
AB  - Consistency and invariance in movements have been seen as the essential features
      of motor skill development. This emphasis on the stabilisation of action has led
      to the neglect of the processes whereby skills are modified and reorganised into
      new and more complex acts, that is the process of adaptation. It is argued that
      variability of motor behaviour has a major role to play in this process and hence
      in the development of skilled actions. The significance of variability for open
      systems and its implications for development are examined. A distinction is made
      between error variability and functional variability, the latter being used in
      the solution of motor problems. Two experiments on the acquisition of a skilled
      action by children are reported. A sequential coincident timing task which
      permitted an operational distinction between the macrostructure and
      microstructure of the task was used. The results support the argument that with
      development the action becomes increasingly consistent at the macrostructure
      level and that this is achieved by maintaining variability at the microstructure
      level.

PMID- 7622411
TI  - Ontogenesis of goal-directed behavior: anatomo-functional considerations.
AB  - Recent neuroanatomical and neurophysiological studies in man have revealed
      ontogenetic events which coincide with broadly defined phases of behavioral and
      cognitive development. During the early fetal period, early produced neurons make
      initial synapses which form the basis for the earliest electrical activity of the
      human brain. The overall immaturity of neuronal connections, in particularly in
      cortical areas, correlates with the absence of any behavioral pattern or goal
      directed movements. In the late fetus and preterm infant, transient accumulation
      of major afferent pathways, the presence of transient layers (subplate zone) and
      transient pattern of transmitter-related organization form the neurological basis
      of cortical electric responses as well as transient behavioral states and sleep
      patterns. Parallel to the profound structural and chemical reorganization of the
      human cerebrum during the first 6 postnatal months there is a disappearance of
      transient behavioral and motor patterns. The previously close spatio-temporal
      correlation between these events becomes progressively looser. The overproduction
      of circuitry elements during the subsequent period peaks in associative cortex
      between 1 and 2 years of age, corresponding to the emergence of skilled actions
      and cognitive functions. After the elimination of some circuitry elements after
      the second year of life, the prolonged maturation of goal-directed behavior and
      the protracted emergence of different cognitive functions correlates with the
      development plateau of synapse production which can be seen up to 16 years of
      age. Parallel to the prolonged maturation of postsynaptic elements, there are
      well defined maturational changes in the chemical properties of associative
      pyramidal neurons of cortical layer III. These findings correspond to the
      prolonged maturation of movement-related brain macropotentials as well as other
      cognition-related potentials, where the last prominent changes were seen after 10
      years of age. Although the coincidence of the developmental events does not
      necessarily mean a causal relationship, the combination of structural and
      physiological data opens new vistas for the further investigation of the
      neurobiological basis of goal-directed movement and cognitive behavior.

PMID- 7622412
TI  - SMANCS.

PMID- 7622413
TI  - Infrequent replication errors at microsatellite loci in tumors of patients with
      multiple primary cancers of the esophagus and various other tissues.
AB  - Patients with esophageal cancer are at high risk of developing other primary
      tumors, especially squamous cell carcinoma in the head and neck. Heavy smoking
      and excessive consumption of alcohol are considered to be crucial environmental
      risk-factors for development of these multiple primary cancers. To investigate
      whether any genetic background, such as defects in the DNA-mismatch repair
      system, may influence the development of these multiple primary tumors, we
      examined replication errors (RER) at six microsatellite loci in DNAs of 46 tumors
      from 33 patients who had developed primary cancers in various tissues in addition
      to the esophagus. RER(+) (RER-positive) phenotype was observed in three tumors in
      two patients of the 33 patients examined. Our results suggested that development
      of multiple primary tumors in these patients would not be affected by an
      abnormality in the DNA repair system(s) detected as the RER phenotype. However,
      it is noteworthy that a single patient who developed multiple cancers revealed
      RER(+) phenotypes at multiple microsatellite loci in both tumors, indicating that
      a defect in the DNA repair gene(s) may have played an important role in the
      development of the tumors in this patient.

PMID- 7622414
TI  - Formation and removal of DNA adducts in the liver of rats chronically fed the
      food-borne carcinogen, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline.
AB  - Effects of chronic administration of 2-amino-3,8-dimethylimidazo[4,5
      f]quinoxaline (MeIQx) at 0.4, 8 and 400 ppm in the diet on DNA adduct formation
      and removal in the rat liver were examined by the 32P-postlabeling method. The
      0.4 and 8 ppm doses for 40 weeks resulted in time-dependent increases in MeIQx
      DNA adduct levels until 16 and 8 weeks, respectively, with constant values being
      maintained thereafter. In the case of a carcinogenic dose (400 ppm) of MeIQx, the
      adduct levels reached a maximum at week 12, and then gradually decreased.
      Alteration of metabolism of MeIQx during liver carcinogensis might be related to
      this decrease in DNA adduct levels. When MeIQx administration was stopped at week
      20, 60-90% of the MeIQx-DNA adducts formed with the three doses (0.4, 8 and 400
      ppm) of MeIQx were removed in a biphasic manner after return to a basal diet,
      with initial rapid removal followed by a slow change. No difference in the
      pattern of MeIQx-DNA adducts was detected on thin layer chromatography at any
      dose at any time point. Thus, it is suggested that there may be at least two
      types of damaged DNA, susceptible and resistant to removal of MeIQx-DNA adducts,
      after chronic administration of MeIQx.

PMID- 7622415
TI  - Effects of apple pectin on fecal bacterial enzymes in azoxymethane-induced rat
      colon carcinogenesis.
AB  - Because of the potential significance of colonic bacteria in colon
      carcinogenesis, we investigated the effect of pectin of different types on fecal
      bacterial enzymes (beta-glucuronidase, beta-glucosidase and tryptophanase) at
      various periods of time after feeding rats with pectin-containing diets during
      azoxymethane-induced colon carcinogenesis. The diet supplemented with 20% apple
      pectin or 20% citrus pectin decreased the multiplicity of colon tumors, and the
      number of tumors was significantly decreased in the group fed apple pectin. The
      incidence of colon tumors in the apple pectin group was lower than that in the
      control group. The mean tumor size was similar among the three groups. Apple
      pectin feeding decreased fecal beta-glucosidase and tryptophanase levels.
      Furthermore, a significant decrease in the activity of beta-glucuronidase was
      observed in the apple pectin group during the initiation phase. These findings
      suggest that the protective effect of pectin on colon carcinogenesis may be
      dependent on the type of pectin and be related to the decrease of beta
      glucuronidase activity in the initiation stage of carcinogenesis.

PMID- 7622416
TI  - Lack of promoting effects of alpha-linolenic, linoleic or palmitic acid on
      urinary bladder carcinogenesis in rats.
AB  - Potential promoting effects of alpha-linolenic, linoleic and palmitic acids were
      investigated in a two-stage urinary bladder carcinogenesis model. In experiment
      1, male F344 rats were given 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in
      their drinking water for 4 weeks and then basal diet containing 10% alpha
      linolenic, 10% linoleic or 10% palmitic acid along with 0.2% butylated
      hydroxyanisole (BHA) as an antioxidant for 24 weeks. The development of tumors in
      the urinary bladder was not increased by treatment with any of the fatty acids.
      In experiment 2, male F344 rats were given 10% alpha-linolenic, 10% linoleic or
      10% palmitic acid along with 0.2% BHA in their diet for 8 weeks without prior BBN
      treatment. The administration of fatty acids was not associated with any increase
      in the 5-bromo-2'-deoxyuridine labeling index of the urinary bladder epithelium.
      Serum and/or urine fatty acid levels increased in the cases of alpha-linolenic
      and linoleic acid treatments, but not with palmitic acid. Under the present
      experimental conditions neither the two polyunsaturated nor the one saturated
      fatty acid exerted any promoting effect on urinary bladder carcinogenesis.

PMID- 7622417
TI  - Altered expression of hepatic CYP1A enzymes in rat hepatocarcinogenesis.
AB  - Hyperplastic nodules of the liver were induced by treating male F344 rats with a
      combination of diethylnitrosamine and partial hepatectomy. The livers were
      examined for the expression of cytochrome P450 (CYP) enzymes, mainly CYP1A1 and
      CYP1A2; the amount and activity of the enzymes in the microsomes were assessed by
      enzymatic and immunological methods. Levels of CYP1A mRNAs were assayed by
      Northern blotting. In the liver bearing hyperplastic nodules, the total amount of
      microsomal CYP enzymes decreased to about 50% of the control. The microsomal
      activities for the CYP1A2-mediated activation of carcinogenic heterocyclic amines
      decreased to about 20% of the corresponding controls, in association with
      decreases in the levels of mRNA and protein of CYP1A2. Furthermore, the
      inducibility of CYP1A2 by CYP1A inducers such as 3-methoxy-4-aminoazobenzene and
      3-methylcholanthrene was also decreased at the mRNA, protein and activity levels.
      On the other hand, CYP1A1 enzyme, which was undetectable in control rat liver,
      appeared in the liver bearing hyperplastic nodules, but its inducibility by a
      CYP1A inducer decreased slightly. The present findings indicated that individual
      CYP1A enzymes are differently regulated, and the expression of CYP1A2 is reduced
      preferentially in the liver bearing hyperplastic nodules.

PMID- 7622418
TI  - Ovarian teratomas in mice lacking the protooncogene c-mos.
AB  - Parthenogenesis has been suggested to be tightly coupled with development of
      ovarian teratomas. Indeed, ovarian tumors developed in c-mos-deficient female
      mice, which are characterized by the parthenogenetic activation of oocytes. The
      tumors appeared at a frequency of 30% between 4 and 8 months of age, and did not
      develop in younger or older mice. Most of the tumors were benign and consisted of
      multi-focal cysts most notably with mature ectodermal components, but also with
      mesodermal and endodermal components. One among 17 tumors observed consisted of
      extra-embryonic tissues alone, and two bore malignant components with metastasis
      to peritoneal organs. The results strongly suggest the involvement of c-mos
      mutations in human germ cell tumors.

PMID- 7622419
TI  - A specific chromosome change and distinctive transforming genes are necessary for
      malignant progression of spontaneous transformation in cultured Chinese hamster
      embryo cells.
AB  - Chinese hamster embryo (CHE) cell strains, each initiated from a separate cell
      stock obtained from different mothers, were transferred successively at intervals
      of 3 days and the changes in growth properties and karyotypes at various passages
      were examined. All nine cell strains proliferated at varying growth rates for 60
      passages but only 2 (designated CHE A1 and CHE A2) of them expressed malignant
      phenotypes. The acquisition of tumorigenicity in nude mice was observed in CHE A1
      and CHE A2 cells at passages 40 and 10, respectively. After 5 passages, 8 of 9
      cell strains contained one or two common additional chromosomes, chromosome 3q
      and/or chromosome 5, although one cell strain (designated CHE A3) maintained a
      normal diploid karyotype for 60 passages. Trisomy of chromosome 3q was observed
      in all tumorigenic CHE A1 and A2 cells. One or two 3q chromosomes were detected
      in all tumor-derived cell lines established from tumors produced by these
      tumorigenic cells. DNA from tumorigenic cells and tumor-derived cell lines
      exhibited a high ability to transform mouse NIH3T3 cells, but we could not detect
      any activation of Ha-ras, Ki-ras, hst, erbB-2, mos, met or raf in any of the
      transformed NIH3T3 cells. These results suggest that even though cultured CHE
      cells can transform spontaneously, without any specific chromosome change, to
      immortal cells, activation of unknown oncogene(s) in addition to a specific
      chromosome change may be required for their malignant progression. Our results
      suggest that trisomy of chromosome 3q is this specific chromosome change.

PMID- 7622420
TI  - Intracranial germ cell tumors: detection of p53 gene mutations by single-strand
      conformation polymorphism analysis.
AB  - Using polymerase chain reaction-single-strand conformation polymorphism (PCR
      SSCP) analysis, p53 gene mutation was examined in 12 intracranial germ cell
      tumors (5 yolk sac carcinomas and 7 germinomas), many of which were derived from
      young patients in the first to the second decade. A total of 10 mutations were
      detected in 4 of the 12 cases and, in 3 of them, the mutations were multiple or
      tandem. Among the 10 mutations, 7 were missense, 1 was splicing and 2 were
      silent. The 7 missense mutations were located at previously proposed hot spot
      codons or in their vicinity or, when outside the hot spots, at a codon encoding
      an amino acid conserved in most vertebrates. These findings suggested that all 7
      missense mutations may actually give rise to functional alteration of the p53
      protein. The splicing mutation was considered to be a germ-line mutation, though
      its biological effect was equivocal, since the neoplastic tissue contained an
      additional mutation. The pattern of the mutations was predominancy of G:C-A:T
      transition with frequent involvement of the CpG site. These mutations were more
      frequently detected in yolk sac carcinomas (60%; 3/5 cases) than in germinomas
      (14%; 1/7 cases), suggesting that the contribution of the p53 mutation to
      carcinogenesis differed with the histological type of the intracranial germ cell
      tumor.

PMID- 7622421
TI  - Cytokine production in five tumor cell lines with activity to induce cancer
      cachexia syndrome in nude mice.
AB  - To identify the so-called toxohormone, which is a tumor-derived factor with
      activity to induce cancer cachexia syndrome in tumor-bearing animals, 5 human
      cancer cell lines with this activity were studied for cytokine production. Tumor
      cell products with activity to inhibit lipoprotein lipase (LPL) were shown to
      play an important role in the development of the cancer cachexia syndrome. All
      culture media conditioned by the 5 cell lines possessed LPL-inhibitory activity.
      However, the activity differed with the cell line. In order to characterize the
      activity, we examined whether the cultured cells produced cytokines with activity
      to inhibit LPL. A melanoma cell line, SEKI, and a neuroepithelioma cell line,
      NAGAI, were found to express a large amount of leukemia inhibitory factor (LIF)
      mRNA. Furthermore, both of these cell lines were demonstrated to produce a large
      amount of LIF protein, and plasma levels of LIF were extremely elevated in SEKI-
      and NAGAI-bearing nude mice, indicating that LIF produced by the tumor cells
      induced cancer cachexia syndrome in the animals. Thus, LIF fulfills the
      requirements for a toxohormone, except for suppressive activity on liver
      catalase. In contrast, the mechanisms responsible for cachexia in the MKN-1-, LX
      1- and LS180-bearing mice remain unknown. These findings suggest that various
      types of bioactive substances produced by cancer cells could be toxohormones.

PMID- 7622422
TI  - Characterization of matrix-degrading proteinases and their inhibitors secreted by
      human gynecological carcinoma cells.
AB  - Matrix-degrading proteinases secreted by tumor cells play crucial roles in tumor
      cell invasion and metastasis. Serum-free conditioned media of 7 human
      gynecological carcinoma cell lines were examined for proteinases and their
      inhibitors by using gelatin zymography, reverse zymography and immunoblotting.
      All of three ovarian adenocarcinoma cell lines secreted urokinase-type
      plasminogen activator. Among them, a mucinous cystadenocarcinoma cell line also
      secreted tissue-type plasminogen activator, plasmin-like enzyme and trypsinogen.
      On the other hand, two ovarian undifferentiated carcinoma cell lines mainly
      secreted glatinase A or B. A choriocarcinoma cell line secreted multiple
      metalloproteinases in the highest amount, whereas an endometrial adenocarcinoma
      cell line (HEC-1) derived from an early clinical stage hardly secreted any
      gelatinolytic enzyme. The five high proteinases producers hardly secreted the
      corresponding inhibitors, such as tissue inhibitor of metalloproteinases (TIMP)
      1, -2 or plasminogen activator inhibitor-1. In contrast to these highly malignant
      cell lines, a poor proteinase producer, HEC-1, secreted a large amount of TIMPs.
      Therefore, an enhanced proteolytic tendency appears to be associated with
      gynecological cancer cells established from highly malignant tumors.

PMID- 7622423
TI  - Simultaneous expression of type IX collagen and an inhibin-related antigen in
      proliferative myoepithelial cells with pleomorphic adenoma of canine mammary
      glands.
AB  - To identify an alcian blue-positive component expressed in the early stage of
      mammary mixed tumor and to pursue the possible involvement of a tumorigenic
      inducing factor, monoclonal antibodies to type IX collagen were generated and
      used to investigate the immunohistochemical kinetics of type IX collagen
      expression by the myoepithelial cell-derived chondrocyte-like cells during the
      development of chondrometaplasia. We also examined the expression of inhibin
      related antigen using antibodies to a synthetic peptide spanning amino acids 1-30
      of the inhibin alpha chain. At the earliest stage of chondrometaplasia, where
      myoepithelial cells began to proliferate inside the basement membrane, the cells
      expressed type IX collagen together with an inhibin-related antigen which was
      immunoreactive with the anti-inhibin peptide antibodies. The expression of the
      inhibin-related antigen was also demonstrated in normal embryonic chondrocytes
      and myoblasts, but was much less strong in mature chondrocytes and myotubes,
      strongly suggesting that the inhibin-related antigen is involved in the
      development of chondrocytes and myoblasts from undifferentiated mesenchymal cells
      as well as proliferating myoepithelial cells as a chondro-progenitor cell in the
      mammary mixed tumor. The pathophysiological significance of type IX collagen
      expression as a possible cell marker of the progenitor cell in myoepithelial cell
      related chondrometaplasia is also discussed.

PMID- 7622424
TI  - Effects of methylxanthine derivatives on adriamycin concentration and antitumor
      activity.
AB  - We studied the mechanism whereby caffeine acts as a biochemical modulator of
      adriamycin, and examined various methylxanthine derivitives to determine whether
      they would be of value as biochemical modulators. In an in vitro study of
      adriamycin efflux in Ehrlich ascites carcinoma cells, theophylline,
      pentoxifylline, and theobromine inhibited this efflux, while caffeine metabolites
      did not. The effects of several methylxanthine derivatives on the antitumor
      activity of adriamycin and on adriamycin concentration in tissue were also
      examined in CDF1 tumor-bearing mice. Theobromine, which inhibited adriamycin
      efflux in vitro, increased the antitumor activity of adriamycin and the
      concentration of adriamycin in tumors. The caffeine metabolites, which had no
      effect on the adriamycin efflux, did not increase antitumor activity. These
      results suggest that the metabolism of caffeine may weaken its effect as a
      biochemical modulator, and that pentoxifylline and theobromine would be of value
      as biochemical modulators of adriamycin.

PMID- 7622425
TI  - Biological effectiveness of fractionated dose of pions in microscopic SCCVII
      tumors: comparison between tumor control dose and tumor growth time assays.
AB  - The relative biological effectiveness (RBE) of fractionated pions for tumor
      growth time (TGT) assay changes with the endpoints, so it is essential to
      determine the RBE for tumor control dose (TCD) assay. For this purpose, the TCD50
      of fractionated pions was compared with that of photons, and the RBEs for TGT and
      TCD assays were concurrently compared as a function of the effect level. A
      "convenient" RBE (cRBE) was substituted for the RBE when the comparison was made
      between similar fractionation schedules with different dose per fraction. SCCVII
      tumors (2 x 10(4) or 2 x 10(5) cells) were implanted into the feet of C3H mice
      and irradiated starting from 2 days after implantation at a total dose range of
      either 9.6-38.4 Gy pions (2.4-6.4 Gy per fraction) or 14.4-50.4 Gy photons (3.6
      7.2 Gy per fraction) in 2-10 fractions over 5-6 days. The cRBE and the RBE at the
      iso-effective level of 30 days TGT were 1.53-1.60 for 2.4-4.8 Gy pions and 1.50
      for 4-fractionated pions, respectively: there were only small differences within
      these schedules used. However, the cRBE values decreased from 1.60 to 1.15 with
      increasing TGT from 30 to 75 days. In contrast, the cRBE values for TCD50
      increased from 1.08 to 1.40 (95% confidence limits [CL]; 1.18-1.63) with
      increasing evaluation time from 60 to 100 days: pions significantly inhibited
      late tumor appearance. The TCD50 at 100 days was 28.7 Gy (CL; 25.0-32.5 Gy) for
      pions and 40.3 Gy (CL; 36.3-44.2 Gy) for photons. In conclusion, the RBE for
      TCD50 was not predictable from the RBE for TGT assay. The cRBE value of 1.4 for
      microscopic tumor control was in close agreement with the reported values for
      skin reaction.

PMID- 7622427
TI  - Salfredins, new aldose reductase inhibitors produced by Crucibulum sp. RF-3817.
      I. Fermentation, isolation and structures of salfredins.
AB  - New inhibitors of aldose reductase, designated salfredins A3, A4, A7, C1, C2, C3
      and B11, were isolated from the fermentation broth of Crucibulum sp. RF-3817 by
      successive purification procedures of solvent extraction, silica gel column
      chromatographies and reverse-phase HPLC. Their structures were established by
      spectroscopic methods, including UV, SI-MS and NMR. The structures of salfredins
      A4 and B11 were confirmed by X-ray crystallographic analysis.

PMID- 7622426
TI  - New flow cytometric method for detection of minimally expressed multidrug
      resistance P-glycoprotein on normal and acute leukemia cells using biotinylated
      MRK16 and streptavidin-RED670 conjugate.
AB  - To evaluate the expression of multidrug resistance (MDR) on normal and leukemia
      cells, we examined P-glycoprotein (P-gp) by a newly devised flow cytometric
      method, utilizing a biotinylated monoclonal antibody (mAb) against P-gp (MRK16),
      a streptavidin-RED670 conjugate (SA-RED670) and appropriate emission filters. The
      combination of biotinylated MRK16 (b-MRK16) and SA-RED670 resulted in higher
      sensitivity as compared with standard methods such as the use of streptavidin
      phycoerythrin (SA-PE) conjugate. The sensitivity was examined in K562, K562/ADR,
      NOMO-1, NOMO-1/ADR and HL60 cells, and compared with the data obtained from
      reverse transcription polymerase chain reaction (RT-PCR) of mdr-1 gene. P-gp
      positivity on flow cytometry was 10.4%, 99.9%, 1.4%, 90.4% and 0%, respectively.
      Mdr-1 mRNA was well expressed in K562/ADR and NOMO-1/ADR cells, but not in NOMO-1
      and HL60 cells. In K562 cells, mdr-1 was found after 40 cycles of PCR, but not 25
      cycles. These data are well correlated with those from the flow cytometry. We
      then studied the P-gp expression on normal peripheral blood cells and acute
      leukemia cells. P-gp was little expressed on peripheral lymphocytes, monocytes
      and granulocytes. It was also little expressed on blast cells from 5 patients
      with acute promyelocytic leukemia (AML) and 5 acute lymphocytic leukemia (ALL)
      expressed P-gp at diagnosis, ranging from 8.5% to 34.5% (16.9 +/- 11.8%) and from
      2.3% to 45.6% (24.0 +/- 17.8%), respectively. All 9 relapsed or refractory cases
      expressed P-gp, ranging from 21.1% to 99.8% (52.2 +/- 29.9%). Significant
      differences were found in APL, CD34-positive and relapse and refractory cases (P
      = 0.0006, 0.0007 and 0.0088, respectively). These results indicate that this flow
      cytometric analysis is useful for the evaluation of clinical MDR status and can
      identify a group of patients with resistant leukemia.

PMID- 7622428
TI  - Isolation, characterization and biological activities of novel triprenyl phenols
      as pancreatic cholesterol esterase inhibitors produced by Stachybotrys sp. F
      1839.
AB  - Ten triprenyl phenol metabolites were isolated as inhibitors of pancreatic
      cholesterol esterase from cultures of Stachybotrys sp. F-1839 by solvent
      extraction and column chromatographies. Combination of spectroscopic analyses
      revealed that two of these compounds are K-76 (1) and stachybotrydial (2), and
      that the remaining eight are new congeners (designated F1839-A (3), -B (4), -C
      (5), -D (6), -E (7), -F (8), -I (9) and -J (10). These compounds inhibited
      pancreatic cholesterol esterase by 50% at 6 x 10(-5) to 1.1 x 10(-1) M.
      Inhibition of the enzyme by compound 2, the most potent one among these
      compounds, was time-dependent and irreversible. When administered to normal rats,
      2, at a single oral dose of 100 mg/kg, reduced [14C]cholesterol absorption by 50
      60%. In cholesterol-fed mice, dietary supplementation of 2 (0.1%) for 14 days
      resulted in a 20% reduction in serum total cholesterol level without causing
      significant change in the high density lipoprotein cholesterol level.

PMID- 7622429
TI  - Balmoralmycin, a new angucyclinone, and two related biosynthetic shunt products
      containing a novel ring system.
AB  - A new angucyclinone, named balmoralmycin (1), was isolated as an inhibitor of
      protein kinase C-alpha (PKC-alpha) from the Streptomyces strain P6417. Chemical
      screening of extracts of the same strain resulted in the detection of two
      decaketides with unusual structural features (2 and 3). Both compounds belong to
      a recently described structural class of secondary metabolites which arises from
      engineered biosynthesis of a recombinant Streptomyces strain. The isolation of
      compounds of this class from a wild-type strain has never been reported before.

PMID- 7622430
TI  - Macquarimicins, microbial metabolites from Micromonospora. I. Discovery,
      taxonomy, fermentation and biological properties.
AB  - A novel series of microbial metabolites were discovered in fermentation broths of
      two soil isolates. Both cultures were identified as strains of Micromonospora
      chalcea. Production of the metabolites, named macquarimicins, was monitored by an
      HPLC assay. A seven-day fermentation yielded 27 mg/liter of macquarimicin A. With
      MICs of 50 to 100 micrograms/ml, macquarimicin A has only very low activity
      against strains of Bacteroides and other anaerobes. Macquarimicin B has
      inhibitory activity against the leukemia cell line P-388.

PMID- 7622431
TI  - Macquarimicins, microbial metabolites from Micromonospora. II. Isolation and
      structural elucidation.
AB  - A novel series of carbocyclic compounds has been isolated from two related
      Micromonospora cultures. The C-19 and C-22 macquarimicins represent different end
      products on a similar biosynthetic scheme. 1-D and 2-D homonuclear and
      heteronuclear NMR experiments allowed assignment of the basic structures of the
      macquarimicins. An X-ray structure of macquarimicin B suggested the
      stereochemistry for the series which was not discernible from spectroscopic data
      alone.

PMID- 7622432
TI  - Thiazinotrienomycins, new ansamycin group antibiotics.
AB  - New triene-ansamycins designated thiazinotrienomycins A, B, C, D and E were
      isolated from culture broth of Streptomyces sp. MJ672-m3 for their activities
      against cervical cancer cell lines. The structures and some biological and
      biochemical properties of the antibiotics were determined.

PMID- 7622433
TI  - Gentamicin formation in Micromonospora purpurea: stimulatory effect of ammonium.
AB  - The effect of ammonium on the fermentative production of gentamicin in
      Micromonospora purpurea has been studied using a chemically defined medium.
      Ammonium chloride concentrations ranging from 20 to 150 mM resulted in a
      proportional stimulation of growth and antibiotic formation. The use of other
      ammonium salts exerted a similar effect. Among the products of ammonium
      assimilation, glutamate and glutamine were able to exert the stimulatory effect.
      In addition, both amino acids reproduced the stimulation in resting cell systems
      of this microorganism and this result was not modified by the presence of
      chloramphenicol, eliminating a possible inductive action as the cause of this
      effect. The use of a glutamine synthetase inhibitor prevented antibiotic
      formation. This inhibition was reverted only by glutamine, suggesting that this
      amino acid was responsible of ammonium stimulation. Glutamine stimulation seems
      to be due to its ability to produce 2-deoxystreptamine and glucosamine,
      intermediates of the gentamicin biosynthetic pathway.

PMID- 7622434
TI  - Production of the new antibiotic tetrahydrokalafungin by transformants of the
      kalafungin producer Streptomyces tanashiensis.
AB  - The new antibiotic tetrahydrokalafungin was produced by the transformants of
      kalafungin producing S. tanashiensis and kalafungin-nonproducing mutants carrying
      the recombinant plasmid pKU523. This plasmid consists of pKU501 (J. Antibiotics
      44: 995 approximately 1005, 1991) which contains the gene cluster for kalafungin
      biosynthesis, and additional 5 kb stability region of SCP2*.

PMID- 7622435
TI  - Concanamycin B inhibits the expression of newly-synthesized MHC class II
      molecules on the cell surface.
AB  - We screened natural chemical compounds which inhibit the expression of newly
      synthesized MHC class II molecules on the cell surface. IFN-gamma stimulates Colo
      205 adenocarcinoma cells to induce the expression of MHC class I, MHC class II,
      and ICAM-1 molecules on the cell surface. We show here that concanamycin B
      inhibits the expression of MHC class II molecules on Colo 205 cells, whereas it
      does not affect the expression of MHC class I and ICAM-1 molecules. Concanamycin
      B also abrogates the enhancement of the MHC class II expression by IL-4 on mouse
      lymphocytes. Furthermore, concanamycin B suppresses the antigen presentation by
      MHC class II molecules.

PMID- 7622436
TI  - Pyripyropenes, Novel ACAT inhibitors produced by Aspergillus fumigatus. III.
      Structure elucidation of pyripyropenes E to L.
AB  - Eight new pyripyropenes, E to L, were isolated from the culture broth of
      Aspergillus fumigatus FO-1289-2501 selected as a higher producer by NTG mutation.
      Structural elucidation indicated that all the pyripyropenes have the same
      pyridino-alpha-pyrone sesquiterpene core as pyripyropenes A to D. Among them,
      pyripyropene L showed the most potent inhibition against acyl-CoA: cholesterol
      acyltransferase (ACAT) activity with an IC50 value of 0.27 microM in rat liver
      microsomes.

PMID- 7622437
TI  - Synthesis and antitumor activities of glycine-exchanged analogs of spicamycin.
AB  - A series of SPM VIII analogs were synthesized to investigate the effect of the
      amino acid moiety on the antitumor activity. The L-threonine analog and the
      glycylglycine analog of SPM VIII showed much higher cytotoxicity to P388 murine
      leukemia cells (IC50 5.8 nM and 0.11 nM, respectively) than SPM VIII (IC50 25nM).
      However, replacement of the glycine moiety with other amino acids greatly reduced
      the antitumor activity against COL-1 human colon cancer xenograft model. This
      study indicated that the glycine moiety of SPM VIII is crucial for the antitumor
      effect.

PMID- 7622439
TI  - Cremeomycin, a novel cytotoxic antibiotic from Streptomyces cremeus. Structure
      elucidation and biological activity.

PMID- 7622438
TI  - Synthesis and antifungal activity of C-16 oximino and vinyl amphotericin B
      derivatives.
AB  - Several new C-16 oximino and vinyl derivatives of amphotericin B are described.
      They are prepared by the reaction of a suitably protected amphotericin B C-16
      aldehyde with hydroxylamine derivatives and Wittig reagents, respectively,
      followed by sequential removal of the protecting groups. The compounds possess
      potent antifungal activity in vitro, similar to or in some cases superior to that
      of amphotericin B itself. With the exception of the C-16 (Z)-methoxime, the new
      derivatives do not show significantly reduced haemolytic activity against
      mammalian erythrocytes compared with amphotericin B.

PMID- 7622440
TI  - Isolation and structure of sorrentanone: a new tetrasubstituted quinone from
      Penicillium chrysogenum.

PMID- 7622441
TI  - Biosynthetic capacities of actinomycetes. 3. Naphthgeranine F, a minor congener
      of the naphthgeranine group produced by Streptomyces violaceus.

PMID- 7622442
TI  - Structures and antifungal activities of new aureobasidins.

PMID- 7622443
TI  - Inhibitory effect of cytostatin on spontaneous lung metastases of B16-BL6
      melanoma cells.

PMID- 7622444
TI  - Synthesis and activity of benzotriazolium cephalosporins.

PMID- 7622445
TI  - Construction of a single component producer from the wild type avermectin
      producer Streptomyces avermitilis.

PMID- 7622446
TI  - The regulation of AP-1 activity by mitogen-activated protein kinases.

PMID- 7622447
TI  - Peroxynitrite-induced apoptosis in HL-60 cells.
AB  - Peroxynitrite (ONOO-), an anion and a potent oxidant, generated by the
      interaction of nitric oxide (NO) and superoxide is able to induce apoptosis in HL
      60 human leukemia cells in a time- and concentration-dependent manner.
      Characteristic morphology of apoptosis can be observed 3 h after HL-60 cells are
      exposed to 10 microM ONOO-. Treatment of HL-60 cells with increasing
      concentrations of ONOO- from 1 to 100 microM confirms the concentration
      dependence of apoptosis as evidenced by: 1) degradation of nuclear DNA of these
      cells into integer multiples of approximately 200 base pairs; 2) colorimetric DNA
      fragmentation assay; and 3) evidence of condensation of chromatin and nuclear
      fragmentation shown by propidium iodide staining. Under the same conditions,
      peroxynitrite causes apoptosis in another transformed cell line, U-937 cells, but
      is ineffective at inducing apoptosis in normal endothelial cells derived from
      human umbilical cord and normal human peripheral blood mononuclear cells. This
      direct evidence of peroxynitrite inducing apoptosis implicated a new function of
      this potent oxidant.

PMID- 7622448
TI  - Cloning and functional expression of a human eosinophil CC chemokine receptor.
AB  - Eosinophils undergo chemotaxis, degranulate, and exhibit [C2+]i changes in
      response to the human CC chemokines macrophage inflammatory protein (MIP)-1
      alpha, regulated on activation, normal T expressed and secreted (RANTES), and
      monocyte chemoattractant protein-3 (MCP-3), but the receptors involved have not
      been defined. We have isolated a human cDNA encoding the first eosinophil
      selective chemokine receptor, designated CC chemokine receptor 3 (CC CKR3). CC
      CKR3 is a seven-transmembrane domain G protein-coupled receptor most closely
      related to the previously reported monocyte- and neutrophil-selective receptor CC
      CKR1 (also known as the MIP-1 alpha/RANTES receptor). When [Ca2+]i changes were
      monitored in stably transfected human embryonic kidney 293 cells, MIP-1 alpha and
      RANTES were both potent agonists for CC CKR3 and CC CKR1. However, MIP-1 beta was
      also an agonist for CC CKR3 but not CC CKR1; MCP-3 was an agonist for CC CKR1 but
      not CC CKR3. CC CKR3 may be one of the host factors responsible for selective
      recruitment of eosinophils to sites of inflammation.

PMID- 7622449
TI  - G beta gamma subunits mediate mitogen-activated protein kinase activation by the
      tyrosine kinase insulin-like growth factor 1 receptor.
AB  - The receptors for insulin-like growth factor 1 (IGF1) and insulin are related
      heterotetrameric proteins which, like the epidermal growth factor (EGF) receptor,
      possess intrinsic ligand-stimulated tyrosine protein kinase activity. In Rat 1
      fibroblasts, stimulation of mitogen-activated protein (MAP) kinase via the IGF1
      receptor and the Gi-coupled receptor for lysophosphatidic acid (LPA), but not via
      the EGF receptor, is sensitive both to pertussis toxin treatment and to cellular
      expression of a specific G beta gamma subunit-binding peptide. The IGF1, LPA, and
      EGF receptor-mediated signals are all sensitive to inhibitors of tyrosine protein
      kinases, require p21ras activation, and are independent of protein kinase C.
      These data suggest that some tyrosine kinase growth factor receptors (e.g. IGF1
      receptor) and classical G protein-coupled receptors (e.g. LPA receptor) employ a
      similar mechanism for mitogenic signaling that involves both tyrosine
      phosphorylation and G beta gamma subunits derived from pertussis toxin-sensitive
      G proteins.

PMID- 7622450
TI  - Identification of a yeast karyopherin heterodimer that targets import substrate
      to mammalian nuclear pore complexes.
AB  - Targeting of import substrate to nuclear pore complexes of permeabilized
      vertebrate cells was previously shown to require a protein complex composed of
      two subunits, termed karyopherin. Yeast contain a homologue of karyopherin alpha
      named Srp1p, which was initially identified as a genetic suppressor of mutations
      in a subunit of RNA polymerase I. To determine whether yeast contain a
      karyopherin complex that includes Srp1p as the karyopherin alpha homologue, we
      genetically replaced Srp1p with a Srp1-Protein A chimera. Cytosol from this
      strain contained a complex, composed of the chimera and a protein of 95 kDa, that
      was purified using affinity chromatography on IgG Sepharose. Microsequence
      analysis showed that the 95-kDa protein was identical with a yeast protein
      encoded by gene L8300.15 on chromosome XII. Sequence comparison revealed that the
      L8300.15 gene product is the closest structural homologue of vertebrate
      karyopherin beta. The yeast alpha and beta karyopherin subunits were expressed in
      Escherichia coli and were purified. When combined, they formed a heterodimeric
      complex and were active in targeting import substrate to nuclear envelopes of
      mammalian cells. We propose that all karyopherins function as alpha/beta
      heterodimers.

PMID- 7622451
TI  - Lipid activation of CTP:phosphocholine cytidylyltransferase is regulated by the
      phosphorylated carboxyl-terminal domain.
AB  - The role of the phosphorylated carboxyl-terminal domain of CTP:phosphocholine
      cytidylyltransferase (CT) in the regulation of enzyme activity was investigated
      by comparing the catalytic properties of wild-type CT to two mutant proteins with
      altered carboxyl-terminal phosphorylation domains. CT isolated from a baculovirus
      expression system was extensively phosphorylated at multiple sites in the
      carboxyl-terminal domain. The CT[S315A] mutant lacked a major CT phosphorylation
      site, and the carboxyl-terminal deletion mutant, CT[delta 312-367], was not
      phosphorylated. The higher activities of CT[delta 312-367] and CT[S315A] relative
      to CT were attributed to differences in the sensitivities of the enzymes to lipid
      activators. The rank order of the apparent Km values for activation by either
      phosphatidylcholine/oleic acid or phosphatidylcholine/diacylglycerol was CT >
      CT[S315A] > CT[delta 312-367]. In addition, CT exhibited negative cooperativity
      in its activation by phosphatidylcholine/oleic acid (nH = 0.64) and
      phosphatidylcholine/diacylglycerol (nH = 0.74) vesicles, whereas CT[delta 312
      367] and CT[S315A] did not. These data support the concept that the
      phosphorylation of the CT carboxyl-terminal domain interferes with the activation
      of CT by lipid regulators.

PMID- 7622452
TI  - Repair of UV-induced (6-4) photoproducts in nucleosome core DNA.
AB  - Using radioimmunoassays, we examined rates of removal of UV-induced pyrimidine
      pyrimidone (6-4) photoproducts ((6-4)PDs) and cyclobutane pyrimidine dimers
      (CPDs) from 146-base pair nucleosome core DNA (and 166-base pair chromatosome
      DNA) of confluent human diploid fibroblasts. Dose-response experiments indicate
      that the yield of (6-4)PDs in core DNA is about 30% that of CPDs in the UV dose
      range of 0-200 J/m2. Repair experiments indicate that, at 40 J/m2, (6-4)PDs are
      removed much faster (approximately 75% in 2 h) from nucleosome core (and
      chromatosome) DNA than CPDs (10-15% in 2 h). A slow rate of removal of CPDs is
      also observed when the UV dose is reduced to 10 J/m2 (i.e. even when the level of
      CPDs is less than that of (6-4)PDs at 40 J/m2). These results indicate that (a)
      the accessibility of repair proteins to (6-4)PDs in nucleosomes is markedly
      different than their accessibility to CPDs and/or (b) repair enzymes are much
      more efficient at incising and removing (6-4)PDs than CPDs in human chromatin.

PMID- 7622453
TI  - Characterization of a Stat-like DNA binding activity in Drosophila melanogaster.
AB  - The cytokine signaling pathways that activate the Janus family of tyrosine
      kinases (Jaks) and the "signal transducers and activators of transcription"
      (Stats) have been well characterized in mammalian systems. Work shown here
      provides evidence that an analogous signaling pathway exists in Drosophila
      melanogaster. Because many of the ligand-receptor pairs in Drosophila have not
      been fully characterized, it was necessary to bypass the receptor stimulation
      event that normally triggers intracellular Jak/Stat activation. This was done by
      treating Drosophila Schneider 2 cells with vanadate/peroxide, which has been
      shown to closely mimic some signaling events triggered by interferon gamma,
      including the activation of Jak1, Jak2, and the Stat1 alpha protein. Evidence
      presented here demonstrates that vanadate/peroxide can induce a gamma response
      region binding complex in Drosophila Schneider 2 cells. This complex contains two
      phosphoproteins of 100 and 150 kDa, respectively, and shares many features with
      the vanadate/peroxide-stimulated binding complex in the mammalian system.
      Southern blot analysis of genomic DNA using the src homology domain 2 (SH2) of
      Stat1 alpha confirms the presence of a related gene in the Drosophila genome.

PMID- 7622454
TI  - NF-kappa B activation by interleukin-1 (IL-1) requires an IL-1 receptor
      associated protein kinase activity.
AB  - An important function of interleukin-1 (IL-1) is activation of the transcription
      factor NF-kappa B, which is signaled via the type I IL-1 receptor (IL-1RI). By
      receptor mutagenesis studies, we have identified a region of the cytoplasmic
      domain of IL-1RI that is required for both IL-1-mediated NF-kappa B activation
      and IL-1-dependent activation of a receptor-associated protein kinase activity we
      term IRAK. No IL-1RI mutants were found that can activate NF-kappa B in the
      absence of IRAK activity. Therefore, we propose that IRAK activation is a
      necessary step in the activation of NF-kappa B by IL-1.

PMID- 7622455
TI  - Preferential inactivation of tissue inhibitor of metalloproteinases-1 that is
      bound to the precursor of matrix metalloproteinase 9 (progelatinase B) by human
      neutrophil elastase.
AB  - The precursor of matrix metalloproteinase 9 (pro-MMP-9) forms a complex with the
      tissue inhibitor of metalloproteinases (TIMP)-1 through the C-terminal domain of
      each molecule, and the N-terminal domain of TIMP-1 in the complex interacts and
      inhibits active MMPs. We have reported that a catalytic amount of MMP-3
      (stromelysin 1) activates pro-MMP-9 (Ogata, Y., Enghild, J. J., and Nagase, H.
      (1992) J. Biol. Chem. 267, 3581-3584). To activate pro-MMP-9 in the complex,
      however, an excess molar amount of MMP-3 is required to saturate the TIMP-1 in
      the complex. The aim of this study was to test the hypothesis that the
      requirement for excess MMP-3 can be circumvented by specific destruction of TIMP
      1 by non-target proteinases. We have tested trypsin, plasmin, cathepsin G,
      neutrophil elastase, and chymotrypsin as possible inactivators of TIMP-1 and
      found that neutrophil elastase inactivates TIMP-1 in the complex without
      significant destruction of pro-MMP-9. Once TIMP-1 is inactivated, pro-MMP-9 can
      be readily activated by a catalytic amount of MMP-3. These results suggest that
      neutrophil elastase may participate in the connective tissue destruction at the
      inflammatory sites not only by its direct action on matrix macromolecules but
      also by rendering pro-MMP-9 in the pro-MMP-9.TIMP-1 complex activable by MMP-3 as
      well as activating pro-MMP-3.

PMID- 7622456
TI  - Novel regulation of chondroitin sulfate glycosaminoglycan modification of amyloid
      precursor protein and its homologue, APLP2.
AB  - Alzheimer's disease is characterized by the presence of parenchymal and
      cerebrovascular deposits of beta-amyloid (A beta). A beta is derived from larger
      amyloid precursor proteins (APP), a member of a family of related polypeptides
      that includes amyloid precursor-like proteins, APLP1 and APLP2. APP and APLP2
      isoforms are encoded by several alternatively spliced APP and APLP2 transcripts,
      respectively. We previously reported that the APLP2-751 isoform is modified by
      the addition of chondroitin sulfate glycosaminoglycan (CS GAG) at Ser-614. In
      this report, we demonstrate that the APLP2-763 isoform, which contains an
      insertion of 12 amino acids immediately N-terminal to Ser-614, is not modified by
      CS GAG. Finally, we demonstrate that like APLP2-751, APP isoforms that lack
      sequences encoded by exon 15 (L-APP) are also modified by CS GAG, whereas APP
      forms containing exon 15 are not. We suggest that CS GAG modification of a subset
      of APP and APLP2 isoforms represents a means of generating functional diversity
      for these polypeptides.

PMID- 7622457
TI  - Characterization and expression of iron regulatory protein 2 (IRP2). Presence of
      multiple IRP2 transcripts regulated by intracellular iron levels.
AB  - Iron regulatory proteins (IRP1 and IRP2) are RNA-binding proteins that bind to
      stem-loop structures, termed iron-responsive elements (IREs), present in either
      the 5'- or 3'-untranslated regions of specific mRNAs. The binding of IRPs to 5'
      IREs inhibits translation of mRNA, whereas the binding of IRPs to 3'-IREs
      stabilizes mRNA. To study the structure and regulation of IRP2, we isolated cDNAs
      for rat and human IRP2. The derived amino acid sequence of rat IPR2 is 93%
      identical with that of human IRP2 and is present in lower eukaryotes, indicating
      that IRP2 is highly conserved. IRP1 and IRP2 share 61% overall amino acid
      identity. IRP2 is ubiquitously expressed in rat tissues, the highest amounts
      present in skeletal muscle and heart. IRP2 is encoded by multiple mRNAs of 6.4,
      4.0, and 3.7 kilobases. The 3'-untranslated region of rat IRP2 contains multiple
      polyadenylation signals, two of which could account for the 4.0-kb and 3.7-kb
      mRNAs. The 3.7-kb mRNA is increased in iron-depleted cells and occurs with a
      reciprocal decrease in the 6.4-kb transcript. These data suggest that the 3.7-kb
      mRNA is produced by alternative poly(A) site utilization in iron-depleted cells.

PMID- 7622458
TI  - Tandem sequence duplications functionally complement deletions in the D1 protein
      of photosystem II.
AB  - Obligate photoheterotrophic mutants of the cyanobacterium Synechocystis sp. PCC
      6803 that carry deletions of conserved residues in the plastoquinone-binding
      niche of the D1 protein were used to select for spontaneous mutations that
      restore photoautotrophic growth. Spontaneous pseudorevertants emerged from two
      deletion mutants, delta YNIV246-9 and delta NN266-7, when the cultures were
      maintained long after the carbon source (glucose) had been depleted from the
      medium and cells had reached stationary phase. Most pseudorevertants were found
      to contain tandem duplications of 6-45-base pair DNA sequences located close to
      the domain carrying the deletion; none of them restored the wild-type sequence.
      Three pseudorevertants isolated from the delta YNIV246-9 mutant contained a
      duplication (7-15 codons) of the DNA sequence immediately downstream of the
      deletion; the protein region encoded by this DNA may include part of the putative
      de helix, an important constituent of the plastoquinone-binding niche. Three
      pseudorevertants isolated from the delta NN266-7 mutant contained duplications
      corresponding to 2-8 amino acid residues adjacent to the site of the deletion. In
      all six pseudorevertants carrying duplications, the length of the D1 protein in
      the modified regions was restored to at least the length present in wild type,
      suggesting that a minimal length of these protein domains may be required for
      functional integrity. In another photoautotrophic strain isolated from delta
      NN266-7, no secondary mutations could be identified in the gene coding for the D1
      protein; such mutations apparently reside on another protein subunit of the
      photosystem II complex. Photosystem II function in the pseudorevertants was
      altered as compared with wild type in terms of growth and oxygen evolution rates,
      photosystem II concentration, the semiquinone equilibrium at the acceptor side,
      and thermostability. A mechanism leading to tandem sequence duplication may
      involve DNA damage followed by DNA synthesis, strand displacement, and ligation.

PMID- 7622459
TI  - Chlorination of tyrosyl residues in peptides by myeloperoxidase and human
      neutrophils.
AB  - Hypochlorous acid is the major strong oxidant generated by human neutrophils, and
      it has the potential to cause much of the tissue damage that these inflammatory
      cells promote. It is produced from hydrogen peroxide and chloride by the heme
      enzyme myeloperoxidase. To unequivocally establish that hypochlorous acid
      contributes to inflammation, a stable and unique marker for its reaction with
      biomolecules needs to be identified. In this investigation we have found that
      reagent hypochlorous acid reacts with tyrosyl residues in small peptides and
      converts them to chlorotyrosine. Purified myeloperoxidase in combination with
      hydrogen peroxide and chloride, as well as stimulated human neutrophils,
      chlorinated tyrosine in the peptide Gly-Gly-Tyr-Arg. Rather than reacting
      directly with the aromatic ring of tyrosine, hypochlorous acid initially reacted
      with an amine group of the peptide to form a chloramine. The chloramine then
      underwent an intramolecular reaction with the tyrosyl residue to convert it to
      chlorotyrosine. This indicates that tyrosyl residues in proteins that are close
      to amine groups will be susceptible to chlorination. Peroxidases are the only
      enzymes capable of chlorinating an aromatic ring. Furthermore, myeloperoxidase is
      the only human enzyme that produces hypochlorous acid under physiological
      conditions. Therefore, chlorotyrosine will be a specific marker for the
      production of hypochlorous acid in vivo and for the involvement of
      myeloperoxidase in inflammatory tissue damage.

PMID- 7622460
TI  - Biosynthesis of phytosiderophores, mugineic acids, associated with methionine
      cycling.
AB  - The biosynthesis of 2'-deoxymugineic acid, a key phytosiderophore, was examined
      in association with the putative methionine recycling pathway in the roots of
      wheat using labeling experiments and structural analysis. Feeding with D-[1
      13C]ribose did not result in 13C enrichment of 2'-deoxymugineic acid, while D-[2
      13C]ribose resulted in 13C enrichment at the C-4", -1, -4' positions, and D-[5
      13C]ribose did in C-1', -4, and -1" positions of 2'-deoxymugineic acid,
      respectively. Furthermore, two isotope-labeled intermediates of the methionine
      recycling pathway, 5-[5-2H2]methylthioribose and 2-[1-13C]keto-4
      methylthiobutyric acid, were synthesized, and their incorporation into 2'
      deoxymugineic acids was investigated. Six deuterium atoms at the C-4, -1', and 
      1" positions of 2'-deoxymugineic acid were observed after feeding with 5-[5
      2H2]methylthioribose. Feeding with 2-[1-13C]keto-4-methylthiobutyric acid yielded
      2'-deoxymugineic acid enriched with 13C at the C-4', -1, and -4" positions. These
      results demonstrated for the first time that the biosynthesis of 2'-deoxymugineic
      acid is associated with the methionine recycling pathway. This association system
      functions to recycle methionine required for continued synthesis of mugineic
      acids in the roots of gramineous plants.

PMID- 7622461
TI  - Molecular variants in the P450c11AS gene as determinants of aldosterone synthase
      activity in the Dahl rat model of hypertension.
AB  - Dahl salt-sensitive (S) and salt-resistant (R) rats are widely used to study
      genetic determinants of salt-sensitive hypertension. Differences in blood
      pressure under a high sodium diet in these two strains may be due to differences
      in the synthesis of 18-OH-11-deoxycorticosterone (18-OH DOC). This difference in
      18-OH-DOC synthesis is due to mutations in the Dahl R rat's gene for P450c11 beta
      (11 beta-hydroxylase), an adrenal enzyme involved in the synthesis of both
      corticosterone and 18-OH DOC from 11-deoxycorticosterone. Aldosterone/renin
      ratios in plasma and in the adrenals are greater in Dahl S than R rats,
      suggesting an altered physiologic relationship between the renin-angiotensin and
      aldosterone systems between these strains. We demonstrate that the mRNA for
      P450c11AS, (aldosterone synthase), an enzyme required for aldosterone synthesis,
      is identical in the Dahl S rat and in normotensive Sprague-Dawley rats, but that
      P450c11AS mRNA from the Dahl R rat contains 7 mutations that result in two amino
      acid substitutions. These two changes result in a form of P450c11AS that has a
      greater apparent Vmax and lower apparent Km, resulting in an enzyme that
      catalyzes the conversion of 11-deoxycorticosterone to aldosterone at a greater
      rate in Dahl R rats than the P450c11AS in Dahl S rats or Sprague-Dawley rats.
      Although plasma and adrenal renin are lower in Dahl S versus R rats, the
      regulation of P450c11AS mRNA expression in rats fed a low and high salt diet are
      identical in these strains. The current findings may explain both the reduced
      aldosterone concentrations and increased aldosterone/renin ratios previously
      reported in the Dahl S versus Dahl R rat.

PMID- 7622462
TI  - Electrogenic properties of the epithelial and neuronal high affinity glutamate
      transporter.
AB  - Active ion-coupled glutamate transport is of critical importance for excitatory
      synaptic transmission, normal cellular function, and epithelial amino acid
      metabolism. We previously reported the cloning of the rabbit intestinal high
      affinity glutamate transporter EAAC1 (Kanai, Y., and Hediger, M. A. (1992) Nature
      360, 467-471), which is expressed in numerous tissues including intestine,
      kidney, liver, heart, and brain. Here, we report a detailed stoichiometric and
      kinetic analysis of EAAC1 expressed in Xenopus laevis oocytes. Uptake studies of
      22Na+ and [14C]glutamate, in combination with measurements of intracellular pH
      with pH microelectrodes gave a glutamate to charge ratio of 1:1, a glutamate to
      Na+ ratio of 1:2, and a OH-/H+ to charge ratio of 1:1. Since transport is K+
      dependent it can be concluded that EAAC1-mediated glutamate transport is coupled
      to the cotransport of 2 Na+ ions, the countertransport of one K+ ion and either
      the countertransport of one OH- ion or the cotransport of 1 H+ ion. We further
      demonstrate that under conditions where the electrochemical gradients for these
      ions are disrupted, EAAC1 runs in reverse, a transport mode which is of
      pathologic importance. 22Na+ uptake studies revealed that there is a low level of
      Na+ uptake in the absence of extracellular glutamate which appears to be
      analogous to the Na+ leak observed for the intestinal Na+/glucose cotransporter
      SGLT1. In voltage clamp studies, reducing extracellular Na+ from 100 to 10 mM
      strongly increased K0.5L-glutamate and decreased I(max). The data indicate that
      Na+ binding at the extracellular transporter surface becomes rate-limiting.
      Studies addressing the cooperativity of the substrate-binding sites indicate that
      there are two distinct Na(+)-binding sites with different affinities and that Na+
      binding is modulated by extracellular glutamate. A hypothetical ordered kinetic
      transport model for EAAC1 is discussed.

PMID- 7622463
TI  - Cloning and expression of a cDNA for a mammalian type III iodothyronine
      deiodinase.
AB  - The type III iodothyronine deiodinase metabolizes the active thyroid hormones
      thyroxine and 3,5,3'-triiodothyronine to inactive compounds. Recently, we have
      characterized a Xenopus laevis cDNA (XL-15) that encodes a selenoprotein with
      type III deiodinase activity (St. Germain, D.L., Schwartzman, R., Croteau, W.,
      Kanamori, A., Wang, Z., Brown, D.D., and Galton, V.A. (1994) Proc. Natl. Acad.
      Sci. U.S.A. 91, 7767-7771). Using the XL-15 as a probe, we screened a rat
      neonatal skin cDNA library. Among the clones isolated was one (rNS43-1) which
      contained a 2.1-kilobase pair cDNA insert that manifested significant homology to
      both the XL-15 and the G21 rat type I deiodinase cDNAs, including the presence of
      an in-frame TGA codon. Expression studies demonstrated that the rNS43-1 cDNA
      encodes a protein with 5-, but not 5'-, deiodinase activity that is resistant to
      inhibition by propylthiouracil and aurothioglucose. Northern analysis
      demonstrated a pattern of tissue expression in the rat consistent with that of
      the type III deiodinase and site directed mutagenesis confirmed that the TGA
      triplet codes for selenocysteine. We conclude that the rNS43-1 cDNA encodes the
      rat type III deiodinase and that the types I and III deiodinases present in
      amphibians and mammals constitute a family of conserved selenoproteins important
      in the metabolism of thyroid hormones.

PMID- 7622464
TI  - Herbimycin A induces the 20 S proteasome- and ubiquitin-dependent degradation of
      receptor tyrosine kinases.
AB  - Herbimycin A is an ansamycin antibiotic isolated as an agent that reverses
      morphological transformation induced by v-src. Although herbimycin A is widely
      used as a tool for inhibiting multiple tyrosine protein kinases and tyrosine
      kinase-activated signal transduction, its mechanism of action is not well defined
      and includes a decrease in both tyrosine kinase protein levels and activity
      (Uehara, Y., Murakami, Y., Sugimoto, Y., and Mizuno, S. (1989) Cancer Res. 49,
      780-785). We now show that herbimycin A induces a profound decrease in the total
      cellular activity of transmembrane tyrosine kinase receptors, such as insulin
      like growth factor, insulin, and epidermal growth factor receptors. A substantial
      proportion of the in vivo inhibition could be explained by an increase in the
      rate of degradation. The enhanced degradation of insulin-like growth factor
      insulin receptor was prevented by inhibitors of the 20S proteasome, whereas
      neither lysosomotropic agents nor general serine- and cysteine-protease
      inhibitors were active in preventing receptor degradation induced by herbimycin
      A. Moreover, in a temperature-sensitive mutant cell line defective in the E1
      catalyzed activation of ubiquitin, herbimycin A treatment at the restrictive
      temperature did not result in the degradation of insulin receptor. These results
      suggest that herbimycin A represents a novel class of drug that targets the
      degradation of tyrosine kinases by the 20S proteasome. The ubiquitin dependence
      of this process indicates that this degradation of tyrosine kinases might involve
      the 20S proteasome as the proteolytic core of the ubiquitin-dependent 26S
      protease.

PMID- 7622465
TI  - Dictyostelium vaults: disruption of the major proteins reveals growth and
      morphological defects and uncovers a new associated protein.
AB  - Vaults are large cytoplasmic ribonucleoprotein particles that are highly
      conserved in both morphology and protein composition. Protein components of
      vaults isolated from Dictyostelium discoideum migrate on SDS-polyacrylamide gels
      as two bands, one at 94 kDa (MvpA) and the other at 92 kDa (MvpB). An MvpB cDNA
      clone was isolated from a Dictyostelium expression library. MvpB shares 60%
      identity with MvpA at the amino acid level. This cDNA has been used to disrupt
      the single mvpB gene in both wild-type and mvpA- genetic backgrounds. Although
      the mvp- mutant lines are viable, they show that loss of MvpA and/or MvpB
      interferes with vault function sufficiently to impede growth under conditions of
      nutritional stress. The resulting mutant cell lines reach stationary phase in
      suspension culture at one-third of the density of wild-type cells. Ovoid
      structures isolated from mvp- single mutant lines represent what remains of
      vaults in these cells. Similar ovoid structures isolated from the mvpA- mvpB-
      line copurify with a newly identified protein of 92 kDa (MvpC), which lacks cross
      reactivity with currently available anti-vault antibodies. Our results indicate
      that the major vault proteins are necessary for optimal cell growth in
      Dictyostelium and reveal an unanticipated complexity in vault composition.

PMID- 7622466
TI  - Stability of wild-type and temperature-sensitive protein subunits of the phage
      P22 capsid.
AB  - Temperature-sensitive folding (tsf) mutants of the phage P22 coat protein prevent
      newly synthesized polypeptide chains from reaching the conformation competent for
      capsid assembly in cells, and can be rescued by the GroEL chaperone (Gordon, C.,
      Sather, S., Casjens, S., and King, J. (1994) J. Biol. Chem. 269, 27941-27951).
      Here we investigate the stabilities of wild-type and four tsf mutant
      unpolymerized subunits. Wild-type coat protein subunits denatured at 40 degrees
      C, with a calorimetric enthalpy of approximately 600 kJ/mol. Comparison with coat
      protein denaturation within the shell lattice (Tm = 87 degrees C, delta H
      approximately 1700 kJ/mol) (Galisteo, M.L., and King, J. (1993) Biophys. J. 65,
      227-235) indicates that protein-protein interactions within the capsid provide
      enormous stabilization. The melting temperatures of the subunits carrying tsf
      substitutions were similar to wild-type. At low temperatures, the tsf mutants,
      but not the wild-type, formed non-covalent dimers, which were dissociated at
      temperatures above 30 degrees C. Spectroscopic and calorimetric studies indicated
      that the mutant proteins have reduced amounts of ordered structure at low
      temperature, as compared to the wild-type protein. Although complex, the in vitro
      phenotypes are consistent with the in vivo finding that the mutants are defective
      in folding, rather than subunit stability. These results suggest a role for
      incompletely folded subunits as precursors in viral capsid assembly, providing a
      mechanism of reaching multiple conformations in the polymerized form.

PMID- 7622467
TI  - A conserved NPLFY sequence contributes to agonist binding and signal transduction
      but is not an internalization signal for the type 1 angiotensin II receptor.
AB  - A conserved NPX2-3Y sequence that is located in the seventh transmembrane helix
      of many G protein-coupled receptors has been predicted to participate in receptor
      signaling and endocytosis. The role of this sequence (NPLFY) in angiotensin II
      receptor function was studied in mutant and wild-type rat type 1a angiotensin II
      receptors transiently expressed in COS-7 cells. The ability of the receptor to
      interact with G proteins and to stimulate inositol phosphate responses was
      markedly impaired by alanine replacement of Asn298 and was reduced by replacement
      of Pro299 or Tyr302. The F301A mutant receptor exhibited normal G protein
      coupling and inositol phosphate responses, and the binding of the peptide
      antagonist, [Sar1,Ile8]angiotensin II, was only slightly affected. However, its
      affinity for angiotensin II and the nonpeptide antagonist losartan was reduced by
      an order of a magnitude, suggesting that angiotensin II and losartan share an
      intramembrane binding site, possibly through their aromatic moieties. None of the
      agonist-occupied mutant receptors, including Y302A and triple alanine
      replacements of Phe301, Tyr302, and Phe304, showed substantial changes in their
      internalization kinetics. These findings demonstrate that the NPLFY sequence of
      the type 1a angiotensin II receptor is not an important determinant of agonist
      induced internalization. However, the Phe301 residue contributes significantly to
      agonist binding, and Asn298 is required for normal receptor activation and signal
      transduction.

PMID- 7622468
TI  - Factor for inversion stimulation-dependent growth rate regulation of serine and
      threonine tRNA species.
AB  - We have previously shown that the accumulation of 20 tRNA species in Escherichia
      coli is individually regulated as a function of cellular growth rate. We have
      also reported that the growth rate regulation of some but not all tRNA species is
      dependent on the activity of the factor for inversion stimulation (FIS). In
      present work, we studied the growth rate regulation of the serine- and threonine
      accepting tRNA families. We show that the levels of tRNA(3Thr), tRNA(3Ser),
      tRNA(2Thr), tRNA(3Thr), and tRNA(4Thr) are reduced in fis cells as the growth
      rate increases. The accumulation of these tRNA species is reduced 2-5-fold at the
      fastest bacterial growth rate. The strongest effect is observed for the two minor
      tRNA species; tRNA(2Ser) and tRNA(2Thr). In contrast, we find that the
      accumulation of tRNA(1Ser), tRNA(5Ser), and tRNA(1Thr) is similar in wild type
      and fis bacteria. The data presented provide further evidence for the suggestion
      that FIS is a stimulating factor that is involved, directly or indirectly, in the
      high expression level of some tRNA genes at fast bacterial growth rates.

PMID- 7622469
TI  - Direct evidence for a role of the "spot 14" protein in the regulation of lipid
      synthesis.
AB  - "Spot 14" is a nuclear protein that is rapidly induced by thyroid hormone (T3)
      and dietary carbohydrate in liver. We used an antisense oligonucleotide to
      inhibit induction of spot 14 protein by T3 and glucose in primary cultures of rat
      hepatocytes to test the hypothesis that the protein could function in the
      regulation of lipid synthesis. Spot 14 protein was undetectable in hepatocytes
      maintained in 5.5 mM glucose without T3, and was induced within 4 h after
      addition of 27.5 mM glucose and 50 nM T3 to the culture medium, reaching a
      maximal level within 24 h. Accumulation of spot 14 protein was markedly inhibited
      in hepatocytes transfected with a spot 14 antisense oligonucleotide, but not in
      those treated with a control oligonucleotide. Transfection of the antisense, but
      not control, oligonucleotide also abrogated the increase in lipogenesis induced
      by T3 and glucose. Reduced triglyceride formation accounted for the diminished
      net lipid synthesis. In contrast to lipogenesis, glucose uptake was not
      significantly affected by the transfections. Antisense transfection inhibited the
      induction of both ATP-citrate lyase and fatty acid synthase immunoreactivities,
      as well as malic enzyme activity, indicating that the observed reduction in
      lipogenesis could be explained by diminished cellular content of lipogenic
      enzymes. Reduced malic enzyme activity in antisense-transfected hepatocytes was
      accompanied by lowered relative abundance of malic enzyme mRNA, suggesting that
      the antisense effects on lipogenic enzymes were mediated at the pretranslational
      level. The oligonucleotides did not significantly affect lipogenesis in a rat
      hepatoma cell line that does not express detectable spot 14 mRNA or protein.
      These data directly implicate the spot 14 protein in the transduction of hormonal
      and dietary signals for increased lipid metabolism in hepatocytes.

PMID- 7622470
TI  - Calcium depletion from the endoplasmic reticulum activates the double-stranded
      RNA-dependent protein kinase (PKR) to inhibit protein synthesis.
AB  - Calcium depletion from the endoplasmic reticulum inhibits protein synthesis and
      correlates with increased phosphorylation of the alpha subunit of eukaryotic
      initiation factor 2 (eIF-2 alpha) by a mechanism that does not require ongoing
      protein synthesis. To elucidate whether protein synthesis inhibition requires eIF
      2 alpha phosphorylation and whether eIF-2 alpha phosphorylation is mediated by
      the double-stranded RNA-dependent protein kinase (PKR), we studied protein
      synthesis in response to calcium depletion mediated by calcium ionophore A23187
      in cell lines overexpressing wild-type eIF-2 alpha, a mutant eIF-2 alpha (S51A)
      that is resistant to phosphorylation, or a dominant negative mutant PKR (K296P in
      catalytic subdomain II). Expression of either mutant eIF-2 alpha or mutant PKR
      partially protected NIH3T3 cells from inhibition of protein synthesis upon A23187
      treatment. In contrast, overexpression of wild-type PKR increased sensitivity to
      protein synthesis inhibition mediated by A23187 treatment. In a COS-1 monkey cell
      transient transfection system, increased eIF-2 alpha phosphorylation in response
      to A23187 treatment was inhibited by expression of the dominant negative PKR
      mutant. Overexpression of the PKR regulatory RNA binding domain, independent of
      the PKR catalytic domain, was sufficient to inhibit increased phosphorylation of
      eIF-2 alpha upon A23187 treatment. In addition, overexpression of the HIV TAR RNA
      binding protein also inhibited eIF-2 alpha phosphorylation upon A23187 treatment.
      Taken together, our data show that calcium depletion activates PKR to
      phosphorylate eIF-2 alpha, and this activation is likely mediated through the PKR
      RNA binding domain.

PMID- 7622471
TI  - Mutation of glutamate 199 of the human C5a receptor defines a binding site for
      ligand distinct from the receptor N terminus.
AB  - C5a, a potent chemoattractant for monocytes, neutrophils, and other leukocytes,
      binds to a cell surface receptor of the seven-transmembrane superfamily. Here we
      report the effects of substituting Gln for Glu199 of the human C5a receptor
      (hC5aR) expressed in a model cell system for chemoattractant receptor signaling,
      the rat basophilic leukemia cell line RBL-2H3. Both the binding affinity for hC5a
      and the EC50 for subsequent cellular signals are reduced 5-10-fold by this
      substitution. A peptide mimic of the C terminus of C5a also binds to, and
      activates, hC5aR. The response to this peptide is reduced in cells bearing
      mutated hC5aR, indicating that the mutation affects interactions with the C
      terminus of hC5a. The C-terminal peptide contains only two basic residues, a Lys
      and an Arg (assumed to be analogous to Lys68 and Arg74 of hC5a), which could act
      as counter-ions for Glu199 of the receptor. If the counter-ion on hC5a was Arg74,
      then it would be expected that intact hC5a and hC5a des-Arg74 would have
      identical affinities and potencies when interacting with mutant hC5aR. It was
      found, however, that the binding affinity and potency (for receptor signaling
      events) of hC5a des-Arg74 was always lower than for intact hC5a. Furthermore, the
      equivalent C-terminal peptide to hC5a des-Arg74 (i.e. lacking the C-terminal Arg)
      could partially activate the wild type but not the mutant receptor, whereas the
      converse peptide, containing Arg but containing Met instead of Lys, had equal
      potencies for both wild type and mutant receptors. Taken together these data
      indicate that Glu199 of hC5aR is not involved in an interaction with Arg74 of
      hC5a, but may interact with Lys68 of hC5a. Mutation of Glu199 defines a second
      ligand binding site on hC5aR, distinct from the previously characterized site on
      the receptor N terminus. Unlike the N-terminal binding site, this second site is
      associated not just with the interaction with hC5a, but also with receptor
      activation.

PMID- 7622473
TI  - Structural and functional roles of asparagine 175 in the cysteine protease
      papain.
AB  - The role of the asparagine residue in the Cys-His-Asn "catalytic triad" of
      cysteine proteases has been investigated by replacing Asn175 in papain by alanine
      and glutamine using site-directed mutagenesis. The mutants were expressed in
      yeast and kinetic parameters determined against the substrate carbobenzoxy-L
      phenylalanyl-(7-amino-4-methylcoumarinyl)- L-arginine. At the optimal pH of 6.5,
      the specificity constant (k(cat)/KM)obs was reduced by factors of 3.4 and 150 for
      the Asn175-->Gln and Asn175-->Ala mutants, respectively. Most of this effect was
      the result of a decrease in k(cat), as neither mutation significantly affected
      KM. Substrate hydrolysis by these mutants is still much faster than the non
      catalytic rate, and therefore Asn175 cannot be considered as an essential
      catalytic residue in the cysteine protease papain. Detailed analyses of the pH
      activity profiles for both mutants allow the evaluation of the role of the Asn175
      side chain on the stability of the active site ion pair and on the intrinsic
      activity of the enzyme. Alteration of the side chain at position 175 was also
      found to increase aggregation and proteolytic susceptibility of the proenzyme and
      to affect the thermal stability of the mature enzyme, reflecting a contribution
      of the asparagine residue to the structural integrity of papain. The strict
      conservation of Asn175 in cysteine proteases might therefore result from a
      combination of functional and structural constraints.

PMID- 7622472
TI  - Heterologous desensitization of opioid-stimulated Ca2+ increase by bradykinin or
      ATP in NG108-15 cells.
AB  - Leucine-enkephalin (Leu-EK) dose-dependently elicited an increase in cytosolic
      Ca2+ concentration ([Ca2+]i) with an EC50 of 1.2 microM via the phosphoinositide
      cascade in NG108-15 cells. Chronic treatment of cells with [D-Ala2,D
      Leu5]enkephalin caused time-dependent homologous desensitization. In the presence
      of extracellular Ca2+, ATP as well as bradykinin stimulated significantly higher
      increases in inositol 1,4,5-trisphosphate (IP3) generation than did Leu-EK;
      however, the magnitude of intracellular Ca2+ pools increased after ATP
      stimulation, whereas bradykinin depleted intracellular pools. Hence, cells lost
      their [Ca2+]i response to Leu-EK if bradykinin was first added to induce a
      [Ca2+]i increase, whereas the response was unchanged if Leu-EK was added after
      addition of ATP. When Leu-EK was added simultaneously with bradykinin or ATP, an
      additive response was observed in IP3 generation; however, the rise in [Ca2+]i
      reached the same level as that induced by bradykinin or ATP alone. In the absence
      of extracellular Ca2+ in which the replenishment of intracellular pools was not
      possible, ATP displayed an inhibitory effect similar to that of bradykinin on the
      Leu-EK-induced [Ca2+]i increase. Prior treatment of cells with Leu-EK slightly
      heterologously desensitized the action of bradykinin, but had no effect on the
      ATP response. Our results suggest that a shared intracellular Ca2+ pool is
      sensitive to the opioid, bradykinin and P2-purinoceptor agonists; however, a
      defined pool of phosphatidylinositol 4,5-bisphosphate or a specific phospholipase
      C is responsible for each receptor.

PMID- 7622474
TI  - Proton-translocating nicotinamide nucleotide transhydrogenase of Escherichia
      coli. Involvement of aspartate 213 in the membrane-intercalating domain of the
      beta subunit in energy transduction.
AB  - Mutations in the beta subunit of Escherichia coli proton-translocating
      nicotinamide nucleotide transhydrogenase of the conserved residue beta Asp-213 to
      Asn (beta D213N) and Ile (beta D213I) resulted in the loss, respectively, of
      about 70% and 90% NADPH-->3-acetylpyridine adenine dinucleotide (AcPyAD)
      transhydrogenation and coupled proton translocation activities. However, the
      cyclic NADP(H)-dependent NADH-->AcPyAD transhydrogenase activities of the mutants
      were only approximately 35% inhibited. The latter transhydrogenation, which is
      not coupled to proton translocation, occurs apparently via NADP under conditions
      that enzyme-NADP(H) complex is stabilized. Mutations beta D213N and beta D213I
      also resulted in decreases in apparent KmNADPH for the NADPH-->AcPyAD and
      S0.5NADPH (NADPH concentration needed for half-maximal activity) for the cyclic
      NADH-->AcPyAD transhydrogenation reactions, and in KdNADPH, as determined by
      equilibrium binding studies on the purified wild-type and the beta D213I mutant
      enzymes. These results point to a structural role of beta Asp-213 in energy
      transduction and are discussed in relation to our previous suggestion that proton
      translocation coupled to NADPH-->NAD (or AcPyAD) transhydrogenation is driven
      mainly by the difference in the binding energies of NADPH and NADP.

PMID- 7622475
TI  - Calcitonin increases cytosolic free calcium concentration via capacitative
      calcium influx.
AB  - The calcitonin receptor has been proposed to function as an extracellular Ca2+
      concentration ([Ca2+]o) sensor (Stroop, S. D., Thompson, D. L., Kuestner, R. E.,
      and Moore, E. E. (1993) J. Biol. Chem. 268, 19927-19930). To test this hypothesis
      we studied the LLC-PK1 renal tubular cells and the PC1 cells, a cell line stably
      transfected with the cloned porcine calcitonin receptor. [Ca2+]i was measured by
      fura-2 single cell microfluorometry. Addition to the cells equilibrated in 1.25
      mM Ca(2+)-containing media of 1-10 mM extracellular Ca2+ did not result in a
      significant increase of [Ca2+]i. Treatment with 10(-7) M salmon calcitonin (sCT)
      elicited a rapid, persistent elevation of [Ca2+]i. Addition of 1-10 mM
      extracellular Ca2+ in the presence of sCT induced a significant [Ca2+]i
      elevation, about 10-fold that observed in the absence of the hormone. Ca2+ influx
      was inhibited by lanthanum. The rise of [Ca2+]i at elevated [Ca2+]o was not due
      to a Ca2+ sensing mechanism with release of Ca2+ from intracellular stores, since
      it was prolonged, and was not abolished by prior depletion of Ca2+ stores with
      10(-6)M thapsigargin. On the contrary, this agent potentiated Ca2+ influx after
      addition of 1-10 mM Ca2+ by 13-fold versus control. Prior stimulation of [Ca2+]i
      with 10(-7) M arginine-vasopressin had similar effects, enhancing the subsequent
      Ca2+ influx. Enhancement of Ca2+ influx by sCT was confirmed by increased Mn2+
      quenching of fura-2 fluorescence. In conclusion, arginine-vasopressin or
      calcitonin enhance Ca2+ influx in LLC-PK1 cells via a Ca2+ release-activated
      conductance, probably dependent upon capacitative Ca2+ entry. Thus, these effects
      are not unique to the calcitonin receptor and argue against the receptor
      functioning as a [Ca2+]o sensor.

PMID- 7622476
TI  - The arterivirus Nsp2 protease. An unusual cysteine protease with primary
      structure similarities to both papain-like and chymotrypsin-like proteases.
AB  - The replicase ORF1a polyprotein of equine arteritis virus, a positive-stranded
      RNA virus, is proteolytically processed into (at least) six nonstructural
      proteins (Nsp). A papain-like Cys protease in Nsp1 and a chymotrypsin-like Ser
      protease in Nsp4 are involved in this process. In this paper we demonstrate that
      the Nsp2/3 junction is not cleaved by either of these previously described
      proteases. Comparative sequence analysis suggested that an additional Cys
      protease resided in the N-terminal Nsp2 domain. For equine arteritis virus, this
      domain was shown to induce Nsp2/3 cleavage in a trans-cleavage assay. Processing
      was abolished when the putative active site residues, Cys-270 and His-332, were
      replaced. Other Nsp2 domains and three other conserved Cys residues were also
      shown to be essential. The Nsp2 Cys protease displays sequence similarity with
      viral papain-like proteases. However, the presumed catalytic Cys-270 is followed
      by a conserved Gly rather than the characteristic Trp. Replacement of Gly-271 by
      Trp abolished the Nsp2/3 cleavage. Conservation of a Cys-Gly dipeptide is a
      hallmark of viral chymotrypsin-like Cys proteases. Thus, the arterivirus Nsp2
      protease is an unusual Cys protease with amino acid sequence similarities to both
      papain-like and chymotrypsin-like proteases.

PMID- 7622477
TI  - Identification of a domain in the angiotensin II type 1 receptor determining Gq
      coupling by the use of receptor chimeras.
AB  - The angiotensin II type 1 (AT1R) and type 2 (AT2R) receptors belong to the seven
      transmembrane receptor superfamily. Previous studies have suggested that the AT1R
      couples to a Gq signaling pathway, whereas the AT2R does not associate with Gq.
      To identify the role that individual intracellular domains play in AT1R function,
      AT1R/AT2R chimeric receptors were prepared by substitution of intracellular
      loops. CHO cells expressing these chimeras were used to test angiotensin II
      induced c-fos expression and Ca2+ mobilization which are involved in the AT1R
      signaling pathway through Gq coupling. Substitution of the second intracellular
      loop (IC2) and the cytoplasmic tail between the two receptors did not affect AT1R
      function. However, exchange of the third intracellular loop (IC3) resulted in the
      loss of function in the AT1R and conferred to the AT2R the ability to
      constitutively activate the fos promoter. These findings suggest that the third
      intracellular loop of the AT1R is critical for Gq coupling. Substitution of
      discrete amino acid sequences of the third intracellular loop indicate that its N
      terminal and C-terminal portions, especially the seven amino acids 219-225 in the
      N-terminal portion, are important for AT1R function, and that the intermediate
      portion of this loop is not required for Gq coupling.

PMID- 7622478
TI  - Related contribution of specific helix 2 and 7 residues to conformational
      activation of the serotonin 5-HT2A receptor.
AB  - A conserved helix 2 Asp is required for the proper function of many G-protein
      coupled receptors. To reveal the structural basis for the role of this residue,
      the additive effects of mutations at this locus and at a conserved helix 7 locus
      were investigated in the 5-HT2A receptor. All mutant receptors studied retained
      high affinity agonist and antagonist binding. Whereas an Asp-->Asn mutation in
      helix 2 eliminated coupling, interchanging the residues at the two positions by a
      second mutation of Asn-->Asp in helix 7 restored receptor function. These data
      suggest that these residues are adjacent in space and interact. The loss of
      function observed with Ala at either position is consistent with each side chain
      forming hydrogen bonds. Molecular dynamics simulations were performed on three
      dimensional computational models of agonist-receptor complexes of both the wild
      type receptor and the Asp-->Asn mutant receptor. Consonant with the lack of
      coupling observed for the mutant construct, introducing the mutation into the
      computational model produced a conformational change in a direction opposite to
      that seen from computational simulations of activation of the wild-type receptor
      model. These results implicate both loci in a common hydrogen-bonding network
      underlying receptor activation by agonist.

PMID- 7622479
TI  - Proteolysis prevents in vivo chimeric fusion protein import into yeast
      mitochondria. Cytosolic cleavage and subcellular distribution.
AB  - The in vivo import of liver mitochondrial aldehyde dehydrogenase was investigated
      in yeast by constructing fusion proteins between its leader sequence and beta
      galactosidase. Only 7% of the protein was imported. If 21 or 71 amino acids from
      the mature portion of aldehyde dehydrogenase were included in the construct, 40%
      was imported. The protein remaining in cytosol was sequenced. When the leader was
      fused directly to beta-galactosidase, the first 7 residues of the leader were
      missing. When 21 residues of mature aldehyde dehydrogenase were included, the
      entire leader plus 6 residues of the mature portion were missing; if 71 residues
      of mature aldehyde dehydrogenase were included, the first residue found
      corresponds to the 66th residue of the mature portion. When the leader was fused
      directly to beta-galactosidase, no processing of the imported protein occurred,
      and the N-terminal amino acid was blocked, presumably by acetylation. If the 21
      amino acid insert was included, processing occurred. A modified leader sequence
      lacking the three-amino acid linker (RGP) was imported but not processed, just as
      we found in vitro (Thornton, K., Wang, Y., Weiner, H., and Gorenstein, D.G.
      (1993) J. Biol. Chem. 268, 19906-19914). The less than 100% import of pre
      aldehyde dehydrogenase was due to the action of a post-translational protease
      attack which prevented import by destroying the leader peptide segment.

PMID- 7622480
TI  - OpuA, an osmotically regulated binding protein-dependent transport system for the
      osmoprotectant glycine betaine in Bacillus subtilis.
AB  - Exogenously provided glycine betaine can efficiently protect Bacillus subtilis
      from the detrimental effects of high osmolarity environments. Through functional
      complementation of an Escherichia coli mutant deficient in glycine betaine uptake
      with a gene library from B. subtilis, we have identified a multicomponent glycine
      betaine transport system, OpuA. Uptake of radiolabeled glycine betaine in B.
      subtilis was found to be osmotically stimulated and was strongly decreased in a
      mutant strain lacking the OpuA transport system. DNA sequence analysis revealed
      that the components of the OpuA system are encoded by anoperon (opuA) comprising
      three structural genes: opuAA, opuAB, and opuAC. The products of these genes
      exhibit features characteristic for binding protein-dependent transport systems
      and in particular show homology to the glycine betaine uptake system ProU from E.
      coli. Expression of the opuA operon is under osmotic control. The transcriptional
      initiation sites of opuA were mapped by high resolution primer extension
      analysis, and two opuA mRNAs were detected that differed by 38 base pairs at
      their 5' ends. Synthesis of the shorter transcript was strongly increased in
      cells grown at high osmolarity, whereas the amount of the longer transcript did
      not vary in response to medium osmolarity. Physical and genetic mapping
      experiments allowed the positioning the opuA operon at 25 degrees on the genetic
      map of B. subtilis.

PMID- 7622482
TI  - Isolation and characterization of a peptide isomerase from funnel web spider
      venom.
AB  - A novel peptide isomerase was purified from the venom of funnel web spider,
      Agelenopsis aperta. The complete primary structure of the isomerase has been
      established by sequence analyses of polypeptide chains, assignments of disulfide
      bridges, carbohydrate analyses, and mass spectrometry of sugar chains. The
      isomerase was found to be a 29-kDa polypeptide that consists of an 18-residue
      light chain and a 243-residue heavy chain connected by a single disulfide bridge.
      The heavy chain contains three intramolecular disulfide bridges and one N-linked
      oligosaccharide chain with a simple trimannosyl core structure. A sequence
      homology search showed a significant similarity of the enzyme with serine
      proteases, particularly around a putative catalytic triad of the isomerase. The
      isomerase specifically interconverts the configuration of Ser46 of a 48-amino
      acid peptide, omega-agatoxin-TK, and the conversion rate from L-Ser to D-Ser was
      approximately two times faster than the reverse reaction.

PMID- 7622481
TI  - Evidence that the Rab3a-binding protein, rabphilin3a, enhances regulated
      secretion. Studies in adrenal chromaffin cells.
AB  - Rabphilin3a had been identified in brain as a Rab3a-binding protein and may serve
      as an effector for Rab3a function. We have cloned a splice variant of brain
      Rabphilin3a from a bovine adrenal chromaffin cell cDNA library and investigated
      the function of the protein in regulated exocytosis in bovine chromaffin cells.
      The predicted amino acid sequence of chromaffin cell (c-) Rabphilin3a was
      identical with that of brain (b-) Rabphilin3a except for a 6-amino-acid insert
      VFSLSA in the amino-terminal half of the protein. An antibody directed against a
      carboxyl-terminal peptide recognized an 85-kDa protein in COS7 cells transfected
      with the cDNA in a mammalian expression vector. A band of similar mobility was
      enriched in a fraction of highly purified chromaffin granule membranes,
      consistent with the Rabphilin3a being associated with chromaffin granule
      membranes. Overexpression of either chromaffin cell or brain Rabphilin3a by
      transfection with the corresponding cDNAs in mammalian expression vectors
      enhanced DMPP-induced secretion of co-expressed human growth hormone (GH)
      approximately 30%. Chromaffin cells transfected with a plasmid with the entire
      coding sequence of c-Rabphilin3a inserted in the antisense orientation inhibited
      secretion of co-expressed GH by approximately 30%. Rabphilin3a mutants lacking
      one or both of the carboxyl-terminal C2 domains strongly inhibited DMPP
      stimulated exocytosis. The single C2 domain deletion also strongly inhibited
      Ca(2+)-dependent secretion from digitonin-permeabilized cells. These data
      indicate that Rabphilin3a is a positive regulator of exocytosis. Because the C2
      deletion mutants contain the amino-terminal Rab3a-GTP binding domain, they may
      inhibit secretion by competing with endogenous Rabphilin3a for interaction with
      Rab3a-GTP without being able to mimic the functional effects of full-length
      Rabphilin3a.

PMID- 7622483
TI  - Characterization and partial amino acid sequencing of a 107-kDa procollagen I N
      proteinase purified by affinity chromatography on immobilized type XIV collagen.
AB  - Procollagen I N-proteinase (EC 3.4.24.14), the enzyme that specifically processes
      type I and type II procollagens to collagen, was isolated from extracts of fetal
      calf skin. After two chromatographic steps on concanavalin A-Sepharose and
      heparin-Sepharose, the semi-purified preparation was used to produce monoclonal
      antibodies. One reacting antibody was found to recognize not the enzyme itself
      but type XIV collagen on which the enzyme was bound. This binding, highly
      sensitive to ionic conditions (plH, salt concentrations) but not affected by non
      ionic detergents, was used for affinity chromatography that strongly improved the
      purification procedure. The enzyme is extensively characterized: 1) it has a
      molecular mass of 107 kDa as determined by polyacrylamide gel electrophoresis in
      presence of SDS and of about 130 kDa when estimated by gel filtration on a
      Sephacryl-S300; 2) in standard assay (pH 7.5, 0.2 M NaCl, 35 degrees C), the
      activation energy for reaction with amino procollagen type I was 17,000 calories
      per mole. In the same conditions, Km and Vmax values were, respectively, 435 and
      39 nM per hour but varied strongly with pH and salt concentration; 3) the enzyme
      cleaved the NH2-terminal propeptide of type I procollagen at the specific site,
      the Pro-Gln bond in the alpha 1 type I procollagen chain; 4) the enzyme contained
      a high proportion of Gly, Asx, and Glx residues but no Hyp or Hyl; 5) partial
      amino acid sequences obtained from internal peptides of the enzyme displayed no
      significant homology with known sequences. The association of procollagen I N
      proteinase with a FACIT (fibril-associated collagens with interrupted triple
      helices) collagen as found here might be of physiological significance.

PMID- 7622484
TI  - Import characteristics of a leucoplast pyruvate kinase are influenced by a 19
      amino-acid domain within the protein.
AB  - Two cDNA clones encoding distinct forms of plastid pyruvate kinase (designated
      Pka and Pkg) have recently been characterized. Pkg is found in both leucoplasts
      and chloroplasts, whereas Pka is present only in leucoplasts. The precursors of
      these proteins have different in vitro import characteristics. The Pkg precursor
      behaves like a typical stromal protein precusor with both types of plastid. In
      contrast, Pka precursors accumulate on the outer envelope membrane of leucoplasts
      under the same assay conditions and require a higher level of ATP for import into
      the organelle. Interestingly, the binding of Pka precursors to chloroplasts
      cannot be detected at any tested level of ATP even though the precursors are
      imported into the organelle at higher concentrations of ATP. Various N-terminal
      deletions and chimeric fusions were used to examine the translocation signaling
      mechanism of the Pka precursor. The N-terminal 83-amino-acid segment of Pka
      contains a transit peptide that is capable of directing dihydrofolate reductase
      and the mature body of Pkg into both types of plastid. Unlike the complete Pka
      precursor, these fusion proteins behave like typical stromal protein precursors.
      The behavior of the Pka transit peptide is influenced by a 19-amino-acid domain (
      P-S-S-I-E-V-D-A-V-T-E-T-E-L-K-E-N-G-F-) located immediately downstream of the N
      terminal 83-residue segment. Deletion of this domain from Pka alters its import
      properties such that it resembles a typical stromal protein precursor. Re
      introduction of the 19-residue domain into the Dhfr fusion protein alters its
      import characteristics to resemble that of the complete Pka precursor. This 19
      amino-acid domain can also influence the function of transit sequences from other
      precursors when it is placed immediately behind the transit peptide. These
      results suggest that this 19-amino-acid domain plays an important role in
      governing the import characteristics of the Pka precursor. We have named this 19
      residue segment the "import modifying domain."

PMID- 7622485
TI  - Purification and characterization of a small membrane-associated sugar phosphate
      phosphatase that is allosterically activated by HPr(Ser(P)) of the
      phosphotransferase system in Lactococcus lactis.
AB  - In the Gram-positive bacterium, Lactococcus lactis, nonmetabolizable cytoplasmic
      sugar phosphates, accumulated by the phosphoenolpyruvate:sugar phosphotransferase
      system, are rapidly dephosphorylated and expelled from the cell upon addition of
      glucose (inducer expulsion). Our recent studies have established that a
      metabolite-activated, ATP-dependent protein kinase that phosphorylates serine-46
      in HPr of the phosphoenolpyruvate:sugar phosphotransferase system activates a
      sugar phosphate phosphatase, thus initiating the inducer expulsion process. A
      membrane-associated, HPr(Ser(P))-dependent phosphatase has been identified,
      solubilized from the membrane, separated from other cellular phosphatases, and
      purified to near homogeneity. It exhibits a low subunit molecular mass (10 kDa)
      and behaves on gel filtration columns like a monomeric enzyme. It has broad
      substrate specificity, optimal activity between pH 7.0 and 8.0, is dependent on a
      divalent cation for activity, and is not inhibited by fluoride. It is stimulated
      more than 10-fold by HPr(Ser(P)) or a mutant derivative of HPr, S46D HPr, in
      which the regulatory serine is changed to aspartate, which bears a permanently
      negative charge as does phosphate. Stimulation is due both to an increase in the
      maximal velocity (Vmax) and a decrease in the Michaelis-Menten kinetic constant
      (Km) for sugar phosphate. The enzyme exhibits a Ka for S46D HPr of 15 microM.
      Although the enzyme is thermally stable, activation by HPr(Ser(P)) is heat
      sensitive.

PMID- 7622486
TI  - Lifetime and reactivity of the veratryl alcohol radical cation. Implications for
      lignin peroxidase catalysis.
AB  - The formation and decay of veratryl alcohol radical cation upon oxidation of
      veratryl alcohol by thallium (II) ions was studied by pulse radiolysis with
      spectrophotometric and conductometric detection. In aqueous solution at pH 3 the
      radical cation decays by a first order process, assigned to the deprotonation
      from the alpha-carbon. On the basis of its lifetime (59 +/- 8 ms) and of its
      ability to oxidize a polymeric dye (Poly R-478) we estimate that the radical
      cation can diffuse about 7 microns in an aqueous environment to act as a mediator
      of oxidations over long distances. However, 4-methoxymandelic acid is not
      oxidized by the veratryl alcohol radical cation in homogeneous solution, and the
      comparison with previous studies on lignin peroxidase catalysis suggests a second
      role for veratryl alcohol radical cation in the enzyme action: it may exist as an
      enzyme-bound species that has either a longer lifetime or a higher reduction
      potential than the free radical cation in bulk solution.

PMID- 7622487
TI  - Interaction of peptides corresponding to fatty acylation sites in proteins with
      model membranes.
AB  - In recent years, a large number of proteins having covalently linked myristic and
      palmitic acids have been discovered. It is assumed that fatty acid acylation
      serves to anchor proteins to membranes. However, it is not clear whether fatty
      acids modulate orientation of peptide chain in membranes or help in associating
      hydrophilic segments of peptides with membranes. We have examined the aggregation
      properties and membrane association of peptides corresponding to myristoylation
      and palmitoylation regions of proteins by fluorescence spectroscopy. Both
      acylated and non-acylated peptides were used for investigation. Binding of the
      peptides to lipid vesicles was assessed by monitoring the fluorescence of
      tryptophan as well as the quenching of its fluorescence in the presence of
      quenchers like I- and acrylamide. Our results indicate that in the peptide
      corresponding to a transmembrane segment, palmitoylation results in a change in
      the orientation of the peptide chain in the lipid bilayer. In the case of
      peptides that do not have a hydrophobic segment, acylation with palmitic or
      myristic acid does not appear to result in increased binding to lipid bilayer.
      Our results suggest that (i) the primary role of myristoylation may not be an
      anchor for membrane attachment as assumed, (ii) palmitoylation in the case of
      proteins having transmembrane segments may serve to realign the transmembrane
      segment from the normal orientation perpendicular to the bilayer surface, (iii)
      in the case of proteins where there is no hydrophobic segment, palmitoylation may
      not serve as a membrane anchor and could be involved in interaction with other
      membrane-bound proteins.

PMID- 7622488
TI  - Glucocorticoid-attenuated response genes encode intercellular mediators,
      including a new C-X-C chemokine.
AB  - A major part of the anti-inflammatory effect of glucocorticoids is attributable
      to their attenuation of the induction of genes whose products mediate
      intercellular interactions, e.g. cytokines and the inducible forms of
      prostaglandin synthase and nitric oxide synthase. We hypothesized that (i) there
      exists a class of immediate-early/primary response genes whose induction by
      inflammatory agents, mitogens, and other stimuli is attenuated by
      glucocorticoids, and (ii) the products of these glucocorticoid-attenuated
      response genes (GARGs) function predominantly in paracrine cell processes. We
      constructed a lambda cDNA library from transforming growth factor beta 1
      pretreated murine Swiss 3T3 cells stimulated with lipopolysaccharide (LPS) or
      serum in the presence of cycloheximide, screened 15,000 plaques by differential
      hybridization, and cloned 12 LPS-induced, dexamethasone-attenuated cDNAs. Seven
      were previously known. Six of these encode intercellular mediators
      (thrombospondin-1, MCSF, JE/MCP-1, MARC/fic/MCP-3, crg2/IP-10, and cyr61); one
      encodes a protein of unknown function (IRG2). Thus, a large majority of these
      GARG cDNAs encode intercellular mediators, as hypothesized. Of the five GARG
      cDNAs not previously known, one encodes a novel member of the CXC chemokine
      family, designated LIX (LPS-induced CXC chemokine). The predicted LIX protein has
      a 40-amino acid signal sequence and a 92-amino acid mature peptide with a
      distinctive COOH-terminal region. Surprisingly, segments of the 3'-untranslated
      regions of LIX and two other CXC chemokines have substantially greater nucleotide
      sequence homology than do their coding regions. These segments may perform an
      unknown regulatory function. The LIX message is strongly induced by LPS in
      fibroblasts, but not in macrophages, suggesting that LIX may participate in the
      recruitment of inflammatory cells by injured or infected tissue.

PMID- 7622489
TI  - Different mechanisms of hydroxylation site selection by liver and kidney
      cytochrome P450 species (CYP27 and CYP24) involved in vitamin D metabolism.
AB  - A series of homologated 1 alpha-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3
      molecules with one to three extra carbons in the side chain were used to examine
      the substrate preferences and hydroxylation site selection mechanisms of the
      liver vitamin D3-25-hydroxylase (CYP27) and the target cell 25-hydroxyvitamin D3
      24-hydroxylase (CYP24). Cultured and transfected cell models, used as sources of
      these hydroxylases, gave 23-, 24-, 25-, and 27-hydroxylated metabolites which
      were identified by their high performance liquid chromatography and GC-MS
      characteristics. Lengthening the side chain is tolerated by each cytochrome P450
      isoform such that 25-hydroxylation or 24-hydroxylation continues to occur at the
      same rate as in the native side chain, while the site of hydroxylation remains
      the same for the liver enzyme in that CYP27 continues to hydroxylate at C-25 and
      C-27 (minor) despite the two-carbon-atom extension. Somewhat surprising is the
      finding that C-24 and C-23 (minor) hydroxylations also do not change as the side
      chain is extended by as much as three carbons. We conclude that CYP24 must be
      directed to its hydroxylation site(s) by the distance of carbon 24 from the
      vitamin D ring structure and not as in CYP27 by the distance of the hydroxylation
      site from the end of the side chain.

PMID- 7622490
TI  - A novel chimeric protein composed of interleukin 13 and Pseudomonas exotoxin is
      highly cytotoxic to human carcinoma cells expressing receptors for interleukin 13
      and interleukin 4.
AB  - Chimeric proteins provide a unique opportunity to target therapeutic bacterial
      toxins to a subset of specific cells. We have generated a new recombinant
      chimeric toxin composed of human interleukin 13 (hIL13) and a Pseudomonas
      exotoxin A (PE) mutant, PE38QQR. The hIL13-PE38QQR chimera is highly cytotoxic to
      cell lines derived from several human epithelial carcinomas such as
      adenocarcinoma of stomach, colon, and skin. The cytotoxic action of hIL13
      PE38QQR, which can only occur upon internalization of ligand-receptor complex, is
      blocked by an excess of hIL13 but not of hIL2. This action is not solely hIL13
      specific because an excess of hIL4 also blocks the cytotoxicity of hIL13-toxin.
      Conversely, hIL13 blocks the cytotoxicity of a hIL4-PE38QQR chimera. Binding
      studies showed that hIL13 displaces competitively 125I-labeled hIL4-PE38QQR on
      carcinoma cells. These results indicate that IL4 and IL13 compete for a common
      binding site on the studied human cell lines. Despite this competition, hIL4 but
      not hIL13 decreased protein synthesis in malignant cells susceptible to the
      cytotoxicity of both hIL13- and hIL4-PE38QQR. Our results suggest that a spectrum
      of human carcinomas express binding sites for IL13. Furthermore, hIL13 and hIL4
      compete reciprocally for a form of the receptor that is internalized upon binding
      a ligand. Thus, cancer cells represent an interesting model for studying
      receptors for these two growth factors. Finally, hIL13-PE38QQR may be a useful
      agent in the treatment of several malignancies.

PMID- 7622491
TI  - Substrate channeling in the lumazine synthase/riboflavin synthase complex of
      Bacillus subtilis.
AB  - The lumazine synthase/riboflavin synthase complex of Bacillus subtilis consists
      of an icosahedral capsid of 60 beta subunits surrounding a core of three alpha
      subunits. The beta subunits catalyze the condensation of 5-amino-6-ribityl-amino
      2,4(1H,3H)-pyrimidinedione (PYR) with 3,4-dihydroxy-2-butanone 4-phosphate (DHB)
      yielding 6,7-dimethyl-8-ribityllumazine. This intermediate is converted to
      riboflavin by the alpha subunits via an unusual dismutation. The second product
      of this reaction is PYR, which is also a substrate of the beta subunits and can
      be recycled in the catalytic process. Sigmoidal kinetics would be expected for
      the formation of riboflavin from PYR and DHB and are indeed observed with
      mixtures of artifactual beta 60 capsids and alpha subunit trimers. In contrast,
      the formation of riboflavin from PYR and DHB by the native alpha 3 beta 60 is
      characterized by a finite initial rate, which is similar to the rate of lumazine
      formation. Most notably, the rate of riboflavin formation has its maximum value
      at t = 0 and decreases dramatically after the consumption of PYR and DHB despite
      the presence of transiently formed lumazine. These data suggest that a
      significant fraction of DHB is converted to riboflavin by substrate channeling,
      which is conducive to an improved overall catalytic rate of riboflavin formation
      at low substrate concentrations. The channel is leaky, and the intermediate
      lumazine is therefore transiently accumulated in the bulk solution. The
      partitioning factor relating the direct formation of riboflavin via substrate
      channeling and the formation of transient 6,7-dimethyl-8-ribityl-lumazine
      increases at low concentrations of the substrates PYR and DHB and has a maximum
      value at pH 7.5. Channeling appears to result from the compartmentalization of
      the alpha subunits inside the icosahedral beta subunit capsid whose catalytic
      sites are located close to the inner capsid surface.

PMID- 7622492
TI  - A new family of conotoxins that blocks voltage-gated sodium channels.
AB  - Conus peptides, including omega-conotoxins and alpha-conotoxins (targeting
      calcium channels and nicotinic acetylcholine receptors, respectively) have been
      useful ligands in neuroscience. In this report, we describe a new family of
      sodium channel ligands, the mu-O-conotoxins. The two peptides characterized, mu-O
      conotoxins MrVIA and MrVIB from Conus marmoreus potently block the sodium
      conductance in Aplysia neurons. This is in marked contrast to standard sodium
      channel blockers that are relatively ineffective in this system. The sequences of
      the peptides are as follows. mu-O-conotoxin MrVIA:
      ACRKKWEYCIVPIIGFIYCCPGLICGPFVCV mu-O-conotoxin MrVIB:
      ACSKKWEYCIVPILGFVYCCPGLICGPFVCV mu-O-conotoxin MrVIA was chemically synthesized
      and proved indistinguishable from the natural product. Surprisingly, the mu-O
      conotoxins show no sequence similarity to the mu-O-conotoxins. However,
      ananalysis of cDNA clones encoding the mu-O-conotoxin MrVIB demonstrated striking
      sequence similarity to omega- and delta-conotoxin precursors. Together, the omega
      , delta-, and mu-O-conotoxins define the O-superfamily of Conus peptides. The
      probable biological role and evolutionary affinities of these peptides are
      discussed.

PMID- 7622493
TI  - The role of histidine 231 in thermolysin-like enzymes. A site-directed
      mutagenesis study.
AB  - In the zinc metallopeptidases produced by the genus Bacillus, an active site
      histidine has been proposed to either stabilize the transition state in catalysis
      by donating a hydrogen bond to the hydrated peptide (Matthews, B. W. (1988) Acc.
      Chem. Res. 21, 333-340) or to polarize a water molecule, which subsequently
      attacks the peptidyl bond (Mock, W. L., and Aksamawati, M. (1994) Biochem. J.
      302, 57-68). Site-directed mutagenesis techniques have been used to change this
      residue in the zinc endopeptidase from Bacillus stearothermophillus to either
      phenylalanine or alanine. At pH 7.0, the kcat/Km values of the substrate leucine
      enkephalin for the phenylalanine and alanine mutants were reduced by factors of
      430- and 500-fold, respectively, as compared with the wild-type enzyme, mostly
      due to changes in kcat. In addition, the enzymatic activities of the mutant
      enzymes showed little pH dependence in the alkaline range, unlike the wild-type
      enzyme. The mutations did not greatly alter the binding affinities of inhibitors
      containing sulfydryl groups to chelate the active site zinc, while those of
      inhibitors containing hydroxamate or carboxylate zinc-chelating groups were
      increased between 80- and 250-fold. The largest change in the binding affinity of
      an inhibitor (> 5 orders of magnitude) was found with the proposed transition
      state mimic, phosphoramidon. The results are generally in agreement with x-ray
      crystallography studies and favor the involvement of the active site histidine in
      transition state binding.

PMID- 7622494
TI  - Colchicine binding by the "isolated" beta-monomer of tubulin.
AB  - At mole ratios of lactoperoxidase to tubulin monomers of 3-4, bovine
      lactoperoxidase forms 1:1 adducts with both alpha- and beta-tubulin from rat
      brain, thereby separating the tubulin heterodimer into its monomers. This mixture
      binds colchicine normally, and we show here by direct photoaffinity labeling that
      the bulk of the [3H]colchicine becomes attached to beta-tubulin under these
      conditions. When the alpha-tubulin has been displaced by lactoperoxidase, the
      ratio of label in beta-tubulin to alpha-tubulin is increased. The amount of label
      in alpha-tubulin decreases with a corresponding appearance of label in
      lactoperoxidase. The rate of labeling of beta-tubulin remains slow. We conclude
      that alpha-tubulin is not necessary for colchicine binding and propose a model
      wherein the A and C rings of colchicine bind to beta-tubulin, while the B ring
      faces alpha-tubulin in the dimer.

PMID- 7622495
TI  - Catalytically active forms of the individual subunits of Vibrio harveyi
      luciferase and their kinetic and binding properties.
AB  - Contradictory findings have recently been reported regarding the (in)abilities of
      individual subunits of the Vibrio harveyi alpha beta dimeric luciferase to
      catalyze bioluminescence. We have produced individual alpha and beta subunits
      separately in Escherichia coli JM109 cells by recombinant DNA techniques. Both
      subunits were purified to more than 90% homogeneity and found to be catalytically
      active, with their general catalytic properties and the specific activities
      similar to those reported earlier (Sinclair, J. F., Waddle, J. J., Waddill, E.
      F., and Baldwin, T. O. (1993) Biochemistry 32, 5036-5044). Individual subunits
      were significantly distinct from the native luciferase with respect to
      inactivations by trypsin and N-ethylmaleimide, and the stability of the flavin 4a
      hydroperoxide intermediate. The active species in isolated alpha and beta samples
      were each the predominant protein species, corresponding to a 42,000 M(r) alpha
      monomer and a 67,000 M(r) beta dimer, respectively. These findings clearly
      indicate that the activities of the individual subunits are not due to trace
      contaminations of the respective counter subunits. The much reduced specific
      activities of the individual subunits are, in part, a consequence of diminished
      abilities to oxidize the aldehyde substrate. Kinetic and equilibrium measurements
      indicate that alpha and beta 2 each contained a reduced flavin site, an aldehyde
      substrate site, and an aldehyde inhibitor site. The on and off rates of the
      decanal inhibitor binding were substantially slower than the bindings of decanal
      and reduced riboflavin 5'-phosphate substrates. These findings are consistent
      with a scheme that the aldehyde inhibitor blocks the binding of the reduced
      flavin substrate.

PMID- 7622496
TI  - Synthesis of medium pyrophosphate by soluble mitochondrial F1 through dimethyl
      sulfoxide-water transitions.
AB  - Soluble F1 from heart mitochondria incubated in mixtures that have Mg2+,
      inorganic phosphate, and dimethyl sulfoxide (40% (v/v)) catalyzes the spontaneous
      synthesis of ATP and pyrophosphate (Tuena de Gomez-Puyou, M., Garcia, J. J., and
      Gomez-Puyou, A. (1993) Biochemistry 32, 2213-2218). By filtration techniques, it
      was determined that synthesized ATP and pyrophosphate are enzyme bound, albeit
      the affinity for pyrophosphate was lower than that of ATP. After ATP and
      pyrophosphate were formed in dimethyl sulfoxide mixtures, dilution with aqueous
      buffer to a dimethyl sulfoxide concentration of 6.0% brought about the partition
      of pyrophosphate into the media. This was evidenced by filtration experiments as
      well as by the accessibility of synthesized pyrophosphate to soluble inorganic
      pyrophosphatase. Release of pyrophosphate induced by dilution occurred in less
      than 15 s. Under conditions that produce release of pyrophosphate, no release of
      ATP was observed; instead, ATP underwent hydrolysis. Studies on the effect of
      arsenate on the synthesis and hydrolysis of ATP and PPi in F1 showed that
      hydrolysis of synthesized PPi at its site of synthesis was slower than that of
      ATP. Thus, the question of whether differences in the rates of hydrolysis
      accounted for the dilution-induced release of PPi but not of ATP was addressed.
      Synthesis and hydrolysis of ATP and pyrophosphate were examined in preparations
      of soluble F1 in complex with its inhibitor protein; the complex had an ATPase
      activity about 100 times lower than that of free F1. In mixtures that contained
      dimethyl sulfoxide, the complex synthesized ATP and pyrophosphate at nearly the
      same rates; upon dilution, hydrolysis of both compounds occurred also at similar
      rates, yet only pyrophosphate was released. The same phenomenon was observed in
      F1 that had been depleted of adenine nucleotides. Hence, dilution-induced release
      of PPi was independent of the overall catalytic properties of the enzyme or its
      content of adenine nucleotides. Since synthesis of ATP occurs at the expense of
      the ADP that remains after depletion of adenine nucleotides, it is likely that
      the failure of ATP to be released is due to the high affinity that F1 exhibits
      for the synthesized ATP. Nevertheless, the results illustrate that a complete
      catalytic cycle that starts with medium Pi and ends with medium pyrophosphate may
      be reproduced in soluble mitochondrial F1.

PMID- 7622498
TI  - A growth hormone agonist produced by targeted mutagenesis at binding site 1.
      Evidence that site 1 regulates bioactivity.
AB  - Growth hormone (GH) is believed to signal by dimerizing its receptor through two
      binding sites on the hormone. Previous attempts to increase the biopotency of GH
      by increasing its site 1 affinity have been unsuccessful, which has led to a bias
      toward engineering site 2 interactions in the quest for creation of super
      agonists. Here we report that increasing site 1 affinity can markedly increase
      proliferative bioactivity in FDC-P1 cells expressing full-length GHR. In
      contrast, we find three site 1 mutants with affinities for site one similar to or
      greater than wild type GH, which have markedly decreased bioactivity. Through
      crystal structure analysis of the receptor interactive regions of these GH
      analogues, we are able to suggest why previous mutagenesis on human GH failed to
      improve biopotency, and thus provide a new avenue for GH and cytokine agonist
      design.

PMID- 7622497
TI  - Inhibition of neurotransmitter release by synthetic proline-rich peptides shows
      that the N-terminal domain of vesicle-associated membrane protein/synaptobrevin
      is critical for neuro-exocytosis.
AB  - Tetanus toxin and clostridial neurotoxins type B, D, F, and G inhibit
      intracellular Ca(2+)-dependent neurotransmitter release via the specific
      proteolytic cleavage of vesicle-associated membrane protein (VAMP)/synaptobrevin,
      a highly conserved 19-kDa integral protein of the small synaptic vesicle
      membrane. This results in the release of the larger part of the cytosolic domain
      of this synaptic protein into the cytoplasm. Microinjection of synthetic peptides
      corresponding to this fragment into identified presynaptic neurons of Aplysia
      californica led to a potent, long lasting, and dose-dependent inhibition
      (approximately 50% at 10 MicroM) of acetylcholine release, probably by hindering
      endogenous VAMP/synaptobrevin from interacting with synaptic proteins involved in
      exocytosis. Structure activity studies showed that this effect is confined to the
      N-terminal domain of VAMP/synaptobrevin isoform II and is related to the presence
      of a proline-rich motif (PGGPXGX3PP or PAAPXGX3PP). At higher concentrations, the
      inhibitory effect was lower and only transient, suggesting that the N-terminal
      proline-rich domain of VAMP/synaptobrevin plays opposing roles in
      neurotransmitter release very likely by interacting with different synaptic
      proteins. This probably occurs by disruption of the recently reported in vitro
      VAMP-synaptophysin interaction that involves the N-terminal domain of VAMP II and
      was proposed to hinder synatophysin-related formation of a fusion pore. The
      observed recovery of neurotransmitter release following injection of high
      concentration of N-terminal fragments of VAMP II brings a strong in vivo support
      to this hypothesis. The minimum active peptide GPGGPQGGMQPPREQS could be used for
      rationally designing potent synthetic blockers of neurotransmission.

PMID- 7622499
TI  - Tertiary structure of uracil-DNA glycosylase inhibitor protein.
AB  - The Bacillus subtilis bacteriophage PBS2 uracil-DNA glycosylase inhibitor (Ugi)
      is an acidic protein of 84 amino acids that inactivates uracil-DNA glycosylase
      from diverse organisms. The secondary structure of Ugi consists of five anti
      parallel beta-strands and two alpha-helices (Balasubramanian, S., Beger, R.D.,
      Bennett, S.E., Mosbaugh, D.W., and Bolton, P.H. (1995) J. Biol. Chem. 270, 296
      303). The tertiary structure of Ugi has been determined by solution state
      multidimensional nuclear magnetic resonance. The Ugi structure contains an area
      of highly negative electrostatic potential produced by the close proximity of a
      number of acidic residues. The unfavorable interactions between these acidic
      residues are apparently accommodated by the stability of the beta-strands. This
      negatively charged region is likely to play an important role in the binding of
      Ugi to uracil-DNA glycosylase.

PMID- 7622500
TI  - Intrasteric regulation of myosin light chain kinase.
AB  - Ca2+/calmodulin activates myosin light chain kinase by reversal of an
      autoinhibited state. The effects of substitution mutations on calmodulin
      activation properties implicate 4 of the 8 basic residues between the catalytic
      core and the calmodulin-binding domain in maintaining autoinhibition. These
      residues are further amino-terminal to the basic residues comprising the
      previously proposed pseudosubstrate sequence and suggest involvement of the
      connecting region in intrasteric autoinhibition. The pseudosubstrate model for
      autoinhibition proposes that basic residues within the autoinhibitory region
      mimic basic residues in the substrate and bind to defined acidic residues within
      the catalytic core. Charge reversal mutations of these specific acidic residues,
      however, had little or no effect on the Km value for regulatory light chain. From
      a total of 20 acidic residues on the surface of the substrate binding lobe of the
      catalytic core, 7 are implicated in binding directly or indirectly to the
      autoinhibitory domain but not to the light chain. Only 2 acidic residues near the
      catalytic site may bind to the autoinhibitory domain and the arginine at P-3 in
      the light chain. Exposure of these 2 residues upon calmodulin binding may be
      necessary and sufficient for light chain phosphorylation.

PMID- 7622501
TI  - Functional mapping of the surface residues of human thrombin.
AB  - Utilizing site-directed mutagenesis, 77 charged and polar residues that are
      highly exposed on the surface of human thrombin were systematically substituted
      with alanine. Functional assays using thrombin mutants identified residues that
      were required for the recognition and cleavage of the procoagulant substrate
      fibrinogen (Lys21, Trp50, Lys52, Asn53 + Thr55, Lys65, His66, Arg68, Tyr71,
      Arg73, Lys77, Lys106 + Lys107, Asp193 + Lys196, Glu202, Glu229, Arg233, Asp234)
      and the anticoagulant substrate protein C (Lys21, Trp50, Lys65, His66, Arg68,
      Tyr71, Arg73, Lys77, Lys106 + Lys107, Glu229, Arg233), interactions with the
      cofactor thrombomodulin (Gln24, Arg70) and inhibition by the thrombin aptamer, an
      oligonucleotide-based thrombin inhibitor (Lys65, His66, Arg70, Tyr71, Arg73).
      Although there is considerable overlap between the functional epitopes, distinct
      and specific residues with unique functions were identified. When the functional
      residues were mapped on the surface of thrombin, they were located on a single
      hemisphere of thrombin that included both the active site cleft and the highly
      basic exosite 1. No functional residues were located on the opposite face of
      thrombin. Residues with procoagulant or anticoagulant functions were not
      spatially separated but interdigitated with residues of opposite or shared
      function. Thus thrombin utilizes the same general surface for substrate
      recognition regardless of substrate function although the critical contact
      residues may vary.

PMID- 7622502
TI  - alpha 1-Antitrypsin Mmalton (Phe52-deleted) forms loop-sheet polymers in vivo.
      Evidence for the C sheet mechanism of polymerization.
AB  - The Z (Glu342-->Lys) and Siiyama (Ser53-->Phe) deficiency variants of alpha 1
      antitrypsin result in the retention of protein in the endoplasmic reticulum of
      the hepatocyte by loop-sheet polymerization in which the reactive center loop of
      one molecule is inserted into a beta-pleated sheet of a second. We show here that
      antitrypsin Mmalton (Phe52-deleted), which is associated with the same liver
      inclusions, is also retained at an endoglycosidase H-sensitive stage of
      processing in the Xenopus oocyte and spontaneously forms polymers in vivo. These
      polymers, obtained from the plasma of an Mmalton/QO (null) bolton heterozygote,
      were much shorter than other antitrypsin polymers and contained a reactive center
      loop-cleaved species. Monomeric mutant antitrypsin was also isolated from the
      plasma. The monomeric component had a normal unfolding transition on transverse
      urea gradient gel electrophoresis and formed polymers in vitro more readily than
      M, but less readily than Z, antitrypsin. The A beta-sheet accommodated a reactive
      center loop peptide much less readily than Z antitrypsin, which in turn was less
      receptive than native M antitrypsin. The nonreceptive conformation of the A sheet
      in antitrypsin Mmalton had little effect on kinetic parameters, the formation of
      SDS-stable complexes, the S to R transition, and the formation of the latent
      conformation. Comparison of the results with similar findings of short chain
      polymers associated with the antithrombin variant Rouen VI (Bruce, D., Perry, D.,
      Borg, J.-Y., Carrell, R. W., and Wardell, M. R. (1994) J. Clin. Invest. 94, 2265
      2274) suggests that polymerization is more complicated than the mechanism
      proposed earlier. The Z, Siiyama, and Mmalton mutations favor a conformational
      change in the antitrypsin molecule to an intermediate between the native and
      latent forms. This would involve a partial overinsertion of the reactive loop
      into the A sheet with displacement of strand 1C and consequent loop-C sheet
      polymerization.

PMID- 7622503
TI  - Sulfated oligosaccharides promote hepatocyte growth factor association and govern
      its mitogenic activity.
AB  - Hepatocyte growth factor (HGF) is a potent mitogen, motogen, and morphogen for
      various epithelial cell types. The pleiotropic effects of HGF are mediated by its
      binding to a specific high affinity receptor, c-Met. In addition, HGF binds to
      heparan sulfate proteoglycans on cell surfaces and within the extracellular
      matrix. Incubation of HGF with 0.1, 1.0, and 10 micrograms/ml of heparin, heparan
      sulfate, or dextran sulfate resulted in a concentration-dependent increase in
      mitogenic potency in a primary rat hepatocyte bioassay, whereas sodium sulfate or
      fucoidan did not. Although co-incubation of HGF with sulfated compounds that
      enhanced HGF-dependent mitogenesis did not alter the binding isotherm of HGF for
      the c-Met receptor in a solid phase assay, an increase in autophosphorylation of
      the c-Met receptor in intact A549 cells was observed upon their addition. A
      series of chemically sulfated malto-oligosaccharides varying in unit size and
      charge was tested in the bioassay in order to provide additional insights into
      the nature of the HGF-heparin interaction. While sulfated di-, tri-, tetra-, and
      pentasaccharides did not significantly potentiate HGF-dependent mitogenesis,
      larger oligosaccharides such as the sulfated hexa-, hepta-, or a sulfated
      oligosaccharide mixture containing decasaccharides resulted in an approximate 2-,
      4-, and 7-fold enhancement, respectively. We observed a correlation between the
      sulfated oligosaccharide preparations that enhanced mitogenic potency and those
      that promoted HGF oligomerization in vitro, as measured by gel filtration and
      analytical ultracentrifugation. These findings indicate that heparin-like
      molecules can stabilize HGF oligomers, which may facilitate c-Met receptor
      dimerization and activation.

PMID- 7622504
TI  - Induction of toxin sensitivity in insect cells by infection with baculovirus
      encoding diphtheria toxin receptor.
AB  - The diphtheria toxin receptor (DTR) has been identified as the precursor of
      heparin-binding epidermal growth factor-like growth factor, which may interact
      with other membrane proteins to form the functional receptor. To test if
      mammalian DTR is able to confer toxin sensitivity onto phylogenetically distant
      cells, we expressed monkey DTR in the baculovirus system and tested infected
      insect cells for toxin sensitivity. cDNA encoding an epitope-tagged heparin
      binding epidermal growth factor-like growth factor precursor (DTRB3) was inserted
      into the virus genome by allelic replacement to construct the recombinant virus
      vAc-DTRB3. SF9 cells infected with vAc-DTRB3 expressed functional DTR, which
      could be precipitated from the solubilized membrane fraction of infected cells
      with Sepharose-immobilized diphtheria toxin. The highest level of expression
      (about 5 x 10(6) receptors/cell) was observed 48 h after infection, at which time
      the infected cells were highly sensitive to diphtheria toxin. Uninfected SF9
      cells and cells infected with the wild type virus were resistant to the toxin.
      The presence of heparin increased both the binding and the toxin sensitivity of
      vAc-DTRB3-infected SF9 cells. Translocation of toxin A fragment was induced when
      cells with surface-bound toxin were exposed to low pH, and the translocation was
      optimal at pH < or = 5.5. It was approximately 100 times more efficient at 24
      degrees C than at 4 degrees C. The data indicate that monkey DTR is fully
      functional when expressed in insect cells.

PMID- 7622506
TI  - Differential interaction with and regulation of multiple G-proteins by the rat A3
      adenosine receptor.
AB  - Interaction of the rat A3 adenosine receptor (A3AR) with G-proteins has been
      assessed using a stably transfected Chinese hamster ovary cell system. The non
      selective AR agonist 5'-N-ethylcarboxamidoadenosine (NECA) increased the labeling
      of a 41-kDa membrane protein by 4-azidoanilido-[alpha-32P]guanosine 5'
      triphosphate (AA-[32P]GTP), a photolabile GTP analogue. Subsequent
      immunoprecipitation of Gi alpha-subunits indicated that NECA stimulated
      incorporation of label into both Gi alpha-2 and Gi alpha-3. Additional
      experiments revealed an A3AR stimulation of label into Gq and/or G11 alpha
      subunits, albeit to a lesser degree than that elicited by endogenous P2U
      purinergic receptors. No interaction with Gs could be detected. Sustained
      cellular exposure to NECA induced A3AR desensitization and specific down
      regulation of Gi alpha-3 and G-protein beta-subunits without changing levels of
      Gi alpha-2, Gs alpha, or Gq+11 alpha-subunits. Therefore the A3AR can interact
      with Gi alpha-2, Gi alpha-3, and, to some extent, Gq-like proteins, but sustained
      agonist exposure down-regulates only one of the G-proteins with which it
      interacts. This is the first description of the differing specificities of A3AR/G
      protein coupling versus down-regulation in situ and provides a potential
      mechanism by which the A3AR could elicit the heterologous desensitization of
      signaling events mediated by Gi3.

PMID- 7622505
TI  - The receptor for urokinase-type plasminogen activator is not essential for mouse
      development or fertility.
AB  - The urokinase-type plasminogen activator receptor (uPAR) gene was disrupted in
      mice in order to explore the role of cell surface-associated plasminogen
      activation in development and hemostasis. Homozygous, uPAR-/- mice were born and
      survived to adulthood with no overt phenotypic abnormalities. There was no
      indication of loss of fetal animals based on the Mendelian pattern of
      transmission of the mutant uPAR gene. uPAR-/- mice carried no detectable uPAR in
      lung, spleen, and other tissues when measured both immunologically by Western
      blot analysis and functionally by ligand cross-linking analyses. In addition,
      activated peritoneal macrophages collected from uPAR-/- mice failed to promote
      plasminogen activation in vitro. The loss of the receptor also resulted in a
      redistribution of uPA in some tissues but had no impact on pro-uPA activation in
      the urogenital tract. Thus, in the absence of other challenging factors such as
      infection, injury, or other functional deficits, uPAR deficiency does not
      compromise fertility, development, or hemostasis. These mice provide a means to
      test the proposed function of uPA/uPAR in wound repair, atherogenesis, and tumor
      cell invasion in vivo.

PMID- 7622507
TI  - Nucleotide-induced conformational changes in the ATPase and substrate binding
      domains of the DnaK chaperone provide evidence for interdomain communication.
AB  - Interactions of the DnaK (Hsp70) chaperone from Escherichia coli with substrates
      are controlled by ATP. Nucleotide-induced changes in DnaK conformation were
      investigated by monitoring changes in tryptic digestion pattern and tryptophan
      fluorescence. Using nucleotide-free DnaK preparations, not only the known ATP
      induced major changes in kinetics and pattern of proteolysis but also minor ADP
      induced changes were detected. Similar ATP-induced conformational changes
      occurred in the DnaK-T199A mutant protein defective in ATPase activity,
      demonstrating that they result from binding, not hydrolysis, of ATP. N-terminal
      sequencing and immunological mapping of tryptic fragments of DnaK identified
      cleavage sites that, upon ATP addition, appeared within the proposed C-terminal
      substrate binding region and disappeared in the N-terminal ATPase domain. They
      hence reflect structural alterations in DnaK correlated to substrate release and
      indicate ATP-dependent domain interactions. Domain interactions are a
      prerequisite for efficient tryptic degradation as fragments of DnaK comprising
      the ATPase and C-terminal domains were highly protease-resistant. Fluorescence
      analysis of the N-terminally located single tryptophan residue of DnaK revealed
      that the known ATP-induced alteration of the emission spectrum, proposed to
      result directly from conformational changes in the ATPase domain, requires the
      presence of the C-terminal domain and therefore mainly results from altered
      domain interaction. Analyses of the C-terminally truncated DnaK163 mutant protein
      revealed that nucleotide-dependent interdomain communication requires a 15-kDa
      segment assumed to constitute the substrate binding site.

PMID- 7622508
TI  - Studies on human aldose reductase. Probing the role of arginine 268 by site
      directed mutagenesis.
AB  - Aldose reductase (ALR2) shows a strong specificity for its nucleotide coenzyme,
      binding NADPH much more tightly than NADH (KD of < 1 microM versus 1.2 mM
      respectively). Interactions responsible for this specificity include salt
      linkages between the highly conserved residues Lys-262 and Arg-268, and the 2'
      phosphate of NADP(H). Previous studies show that mutation of Lys-262 results in
      an increase in the Km for both coenzyme and aldehyde substrate, as well as in the
      kcat of reduction. The present study shows that mutation of Arg-268 to methionine
      results in a 36-fold increase in Km and 205-fold increase in KD for NADPH, but
      little change in Km for DL-glyceraldehyde or in the kcat of the reaction.
      Calculation of free energy changes show that the 2'-phosphate of NADPH
      contributes 4.7 kcal/mol of binding energy to its interaction with WT-hALR2. For
      the R268M mutant, the interaction of NADPH was destabilized by 3.2 kcal/mol,
      indicating that the mutation decreases the binding energy of NADPH by 65%. The
      effect of removing Arg-268 in the absence of the 2'-phosphate of NADPH was
      virtually identical to the destabilization of the activation energy in the
      absence of the 2'-phosphate itself (1.9 versus 2.0 kcal/mol, respectively).
      Therefore, while the 2'-phosphate of the coenzyme plays a role in both coenzyme
      binding and transition state stabilization during catalysis, the role of Arg-268
      lies strictly in tighter coenzyme binding.

PMID- 7622509
TI  - Glucose catabolism in cancer cells. Isolation, sequence, and activity of the
      promoter for type II hexokinase.
AB  - One of the most characteristic phenotypes of rapidly growing cancer cells is
      their propensity to catabolize glucose at high rates. Type II hexokinase, which
      is expressed at high levels in such cells and bound to the outer mitochondrial
      membrane, has been implicated as a major player in this aberrant metabolism. Here
      we report the isolation and sequence of a 4.3-kilobase pair proximal promoter
      region of the Type II hexokinase gene from a rapidly growing, highly glycolytic
      hepatoma cell line (AS-30D). Analysis of the sequence enabled the identification
      of putative promoter elements, including a TATA box, a CAAT element, several Sp-1
      sites, and response elements for glucose, insulin, cAMP, Ap-1, and a number of
      other factors. Transfection experiments with AS-30D cells showed that promoter
      activity was enhanced 3.4-, 3.3-, 2.4-, 2.1-, and 1.3-fold, respectively, by
      glucose, phorbol 12-myristate 13-acetate (a phorbol ester), insulin, cAMP, and
      glucagon. In transfected hepatocytes, these same agents produced little or no
      effect. The results emphasize normal versus tumor cell differences in the
      regulation of Type II hexokinase and indicate that transcription of the Type II
      tumor gene may occur independent of metabolic state, thus, providing the cancer
      cell with a selective advantage over its cell of origin.

PMID- 7622510
TI  - Nucleotide labeling and reconstitution of the recombinant 58-kDa subunit of the
      vacuolar proton-translocating ATPase.
AB  - Evidence suggests that ATP hydrolysis catalyzed by the clathrin-coated vesicle
      proton-translocating ATPase requires at least four polypeptides of molecular
      masses of 70, 58, 40, and 33 kDa (Xie, X.-S., and Stone, D.K. (1988) J. Biol.
      Chem. 263, 9859-9867). To further investigate the subunit requirements for ATP
      hydrolysis, histidine-tagged, 58-kDa polypeptide was expressed in insect Sf9
      (Spodoptera frugiperda) cells. After purification by Ni(2+)-nitrolotriacetic acid
      chromatography, the 58-kDa protein was found to lack significant ATPase activity.
      However, the subunit was photoaffinity labeled with [alpha-32P]ATP, [14C]ADP, or
      35S-labeled ADP and UV irradiation in a divalent cation-dependent manner. The
      labeling was saturable with an apparent Kd of 4 microM for both ATP and ADP. ATP
      and ADP competition labeling experiments indicate that the two nucleotides share
      the same binding site. When reconstituted with recombinant 70-kDa subunit and a
      biochemically prepared catalytic sector (Vc) depleted of the 70- and 58-kDa
      subunits, the 58-kDa component restores Ca(2+)-activated ATP hydrolysis to a
      specific activity of 0.19 mumol Pi x mg protein-1 x min-1, thus demonstrating
      that ATP hydrolysis in vacuolar type proton pumps is dependent upon the 58-kDa
      subunit as well as multi-subunit interactions.

PMID- 7622511
TI  - Sorting of cytochrome b2 to the intermembrane space of mitochondria. Kinetic
      analysis of intermediates demonstrates passage through the matrix.
AB  - Precytochrome b2 is targeted to the mitochondrial intermembrane space by a dual
      targeting sequence comprising 80 amino acids. A kinetic analysis of
      intramitochondrial sorting was performed. The intermediate-size form accumulated
      transiently in the matrix. When import was performed in the presence of metal
      chelators to prevent the first processing by the matrix processing peptidase, >
      40% of the imported precursor was localized in the matrix. A deletion of 13 amino
      acids in the intermembrane space sorting sequence caused partial inhibition of
      the first processing, and a transient accumulation of the precursor form in the
      matrix was also observed. The decrease in this matrix-localized precursor form
      paralleled an increase in the mature-size form in the intermembrane space. A
      point mutation in the mitochondrial targeting sequence (N-terminal to the sorting
      sequence) resulted in missorting to the matrix space. Furthermore, a chimeric
      protein consisting of the initial 85 residues of cytochrome b2 fused to
      dihydrofolate reductase was partially targeted to the matrix at 15 degrees C, but
      not at 25 degrees C. Together, the results presented here indicate that
      cytochrome b2 passes through the matrix on its sorting pathway to the
      intermembrane space.

PMID- 7622512
TI  - Cloning and molecular analysis of the pea seedling copper amine oxidase.
AB  - A pea seedling amine oxidase cDNA has been isolated and sequenced. A single long
      open reading frame has amino acid sequences corresponding to those determined
      from active site peptide (Janes, S.M., Palcic, M.M., Scaman, C.H., Smith, A.J.,
      Brown, D.E., Dooley, D.M., Mure, M., and Klinman, J.P. (1992) Biochemistry 31,
      12147-12154) and N-terminal sequencing experiments. The latter reveals the
      protein to have a 25-amino acid leader sequence with characteristics of a
      secretion signal peptide, as expected for this extracellular enzyme. Comparisons
      of the amino acid sequence of the mature pea enzyme (649 amino acids) with that
      of the mature lentil enzyme (569 amino acids; Rossi, A., Petruzzelli, R., and
      Finazzi-Agro, A. (1992) FEBS Lett. 301, 253-257) reveal important and unexpected
      differences particularly with regard to protein length. Sequencing of part of the
      lentil gene identified several frameshift differences within the coding region
      resulting in a mature lentil protein of exactly the same length, 649 amino acids,
      as the pea enzyme. Multiple alignments of 10 copper amine oxidase sequences
      reveal 33 completely conserved residues of which 10 are found within 41 aligned
      residues at the C-terminal tails, the region missing from the original lentil
      sequence. One of only four conserved histidines is found in this region and may
      represent the third ligand to the copper. The pea enzyme contains around 3-4%
      carbohydrate as judged by deglycosylation experiments. We have also demonstrated
      by hybridization analysis that copper amine oxidase genes are present in a range
      of mono- and dicotyledonous plants.

PMID- 7622513
TI  - Kinetic analysis of a recombinant UDP-N-acetyl-D-galactosamine: polypeptide N
      acetylgalactosaminyltransferase.
AB  - A mammalian expression vector was designed to express a secreted soluble form of
      the UDP-GalNAc: polypeptide N-acetylgalactosaminyltransferase (polypeptide GalNAc
      transferase) with a metal binding site (HHWHHH) at the NH2 terminus. The
      recombinant enzyme was purified to homogeneity from COS-7 cell media by
      sequential chromatography on columns of NiCl2-chelating Sepharose, Affi-Gel blue,
      and Sephacryl S-100. Kinetic parameters of recombinant and native polypeptide
      GalNAc transferase were comparable for the donor UDP-GalNAc and for the peptide
      acceptor AcTPPP, EPO-T (PPDAATAAPLR), and HVF (PHMAQVTVGPGL). Initial velocity
      and product inhibition studies were carried out with purified recombinant
      polypeptide GalNAc transferase and the substrates UDP-GalNAc and peptide EPO-T.
      Initial velocity data was consistent with a sequential type mechanism in which
      binding of both substrates precedes product release. Product inhibition analysis
      using UDP showed competitive inhibition against UDP-GalNAc and a noncompetitive
      inhibition against peptide EPO-T. The dead end peptide analogue EPO-G
      (PPDAAGAAPLR) was a noncompetitive inhibitor of UDP-GalNAc and a competitive
      inhibitor of peptide EPO-T. Collectively, the results suggest that the most
      probable kinetic mechanism for the enzyme is one in which both substrates must
      bind in a random order prior to catalysis. Interestingly, the Km for EPO-T is
      similar to the Ki for EPO-G, suggesting that peptide interaction with the
      polypeptide GalNAc transferase does not require a hydroxyamino acid.

PMID- 7622514
TI  - The N-ethylmaleimide-sensitive fusion protein and alpha-SNAP induce a
      conformational change in syntaxin.
AB  - The N-ethylmaleimide-sensitive fusion protein (NSF) plays an essential role in
      intracellular membrane fusion events and has been implicated in the exocytosis of
      synaptic vesicles. NSF binds through soluble NSF attachment proteins (SNAPs) to a
      complex of neuronal membrane proteins comprised of synaptobrevin, syntaxin, and
      SNAP-25. Disassembly of this complex by NSF is thought to be a critical step in
      the molecular events which lead to vesicle fusion with the plasma membrane. Here
      we have studied the interaction of alpha-SNAP and NSF with individual components
      of this complex and have identified syntaxin as a primary substrate for NSF/alpha
      SNAP. We find that alpha-SNAP binds directly to syntaxin 1A as well as weakly to
      SNAP-25, while it does not bind to synaptobrevin II. NSF binds to syntaxin
      through alpha-SNAP and in the presence of ATP catalyzes a conformational
      rearrangement which abolishes binding of itself and alpha-SNAP. This reaction
      leads to the previously described disassembly of the fusion complex, since
      synaptobrevin binding to syntaxin is also reduced. alpha-SNAP binds to a carboxyl
      terminal syntaxin fragment (residues 194-288) that also binds synaptobrevin and
      SNAP-25. However, NSF action on this syntaxin fragment has no effect on the
      binding of alpha-SNAP or synaptobrevin. This suggests that the conformational
      change normally induced by NSF in syntaxin depends on an interaction between
      carboxyl- and amino-terminal domains of syntaxin.

PMID- 7622515
TI  - Discovery of an epidermal stearoyl-acyl carrier protein thioesterase. Its
      potential role in wax biosynthesis.
AB  - Plant epicuticular, or surface, waxes are synthesized primarily, if not
      exclusively, by epidermal cells. The epicuticular wax constitutes almost 20% of
      the chloroform-extractable lipids in developing leek leaf and is derived
      predominantly from saturated fatty acids. The significant requirement for
      saturated fatty acids in epidermal tissues led us to investigate whether or not
      epidermal extracts have thioesterase activities that prefer saturated acyl-acyl
      carrier protein (ACP) substrates, rather than the 18:1-ACP more commonly
      hydrolyzed by total leaf extracts. Epidermal extracts from Brassica, pea, and
      leek exhibited higher activities toward saturated acyl-ACPs relative to 18:1-ACP
      when compared to total leaf or leaf parenchymal extracts. We identified and
      purified a stearoyl-ACP (18:0-ACP)-specific thioesterase from leek epidermal
      extracts which could be separated from 18:1-ACP thioesterase using hydroxyapatite
      chromatography. The stearoyl-ACP thioesterase exhibited a high preference for
      18:0-ACP, having less than 10% of the 18:0-ACP hydrolyzing activity when
      presented with 18:1-ACP, 16:0-ACP, or 18:0-CoA substrates. The stearoyl-ACP
      thioesterase was predominantly, if not exclusively, expressed in epidermis and
      may play a role in generating the saturated fatty acid pool required for wax
      production.

PMID- 7622516
TI  - Perilipins are associated with cholesteryl ester droplets in steroidogenic
      adrenal cortical and Leydig cells.
AB  - Steroidogenic cells store cholesteryl esters, precursors for steroid hormone
      synthesis, in intracellular lipid droplets. Cholesteryl ester hydrolysis is
      activated by protein kinase A and catalyzed by cholesteryl esterase. The esterase
      is similar, if not identical, to hormone-sensitive lipase in adipocytes where an
      analogous lipolytic mechanism occurs. Perilipins, proteins located exclusively at
      lipid droplet surfaces in adipocytes, are polyphosphorylated by protein kinase A
      in response to lipolytic stimuli, suggesting a role for these proteins in
      mediating lipid metabolism. The present study reveals that perilipins are
      associated with cholesteryl ester droplets in two steroidogenic cell lines: Y-1
      adrenal cortical cells and MA-10 Leydig cells. The relative abundance of
      perilipin mRNAs and protein is much less in steroidogenic cells than in
      adipocytes. Like adipocytes, steroidogenic cells express perilipin A;
      additionally, the latter cells contain relatively abundant amounts of perilipin
      C, a protein that is not detectable in adipocytes by Western analysis. The data
      suggest a strong link between perilipins and lipid hydrolysis that is mediated by
      the hormone-sensitive lipase/cholesteryl esterase class of enzymes.

PMID- 7622517
TI  - Topological mapping of neutrophil cytochrome b epitopes with phage-display
      libraries.
AB  - Cytochrome b of human neutrophils is the central component of the microbicidal
      NADPH-oxidase system. However, the folding topology of this integral membrane
      protein remains undetermined. Two random-sequence bacteriophage peptide libraries
      were used to map structural features of cytochrome b by determining the epitopes
      of monoclonal antibodies (mAbs) 44.1 and 54.1, specific for the p22phox and
      gp91phox cytochrome b chains, respectively. The unique peptides of phage selected
      by mAb affinity purification were deduced from the phage DNA sequences. Phage
      selected by mAb 44.1 displayed the consensus peptide sequence GGPQVXPI, which is
      nearly identical to 181GGPQVNPI18 of p22phox. Phage selected by mAb 54.1
      displayed the consensus sequence PKXAVDGP, which resembles 382PKIAVDGP389 of
      gp91phox. Western blotting demonstrated specific binding of each mAb to the
      respective cytochrome b subunit and selected phage peptides. In flow cytometric
      analysis, mAb 44.1 bound only permeabilized neutrophils, while 54.1 did not bind
      intact or permeabilized cells. However, mAb 54.1 immunosedimented detergent
      solubilized cytochrome b in sucrose gradients. These results suggest the
      181GGPQVNPI188 segment of p22phox is accessible on its intracellular surface, but
      the 382PKIAVDGP389 region on gp91phox is not accessible to antibody, and probably
      not on the protein surface.

PMID- 7622518
TI  - Relationship between P-box amino acid sequence and DNA binding specificity of the
      thyroid hormone receptor. The effects of half-site sequence in everted repeats.
AB  - The three P-box amino acids in the DNA recognition alpha-helix of steroid/thyroid
      hormone receptors participate in the discrimination of the central base pairs of
      the hexameric half-sites of receptor response elements in DNA. A series of 57
      variants of the beta isoform of the human thyroid hormone receptor were
      constructed in which the 19 possible amino acid substitutions were incorporated
      at each of the three P-box positions. The effects of these substitutions on the
      sequence specificity of the DNA binding activity of the receptor were analyzed
      using 16 everted repeat elements which differed in sequence in the two central
      base pairs of the hexameric half-sites. Only receptors with glutamate or
      aspartate as the first P-box amino acid had detectable DNA binding affinity on
      everted repeats with AGGNCA half-sites. Only those receptors with alanine,
      glycine, serine, or proline in the second P-box position were able to bind to
      this same group of everted repeat elements. In contrast, many of the variant
      receptors with substitutions at the third P-box position were capable of binding
      to the AGGNCA group of repeat elements. The actual substitutions at the third P
      box position that were compatible with binding depended upon the identity of the
      fourth base pair of the AGGNCA half-sites. Of the remaining 12 everted repeat
      sequences, only those with AGTTCA or AGTCCA half-sites were able to bind any of
      the receptors. In addition to wild type receptor, several variant receptors with
      amino acid substitutions in either the first or third P-box position were able to
      bind to the everted repeat with AGTTCA half-sites. The everted repeat with AGTCCA
      half-sites was bound by receptors with a DGG, NGG, or EGQ P-box sequence, but not
      the wild type receptor which has an EGG P-box sequence. These data demonstrate
      that all three P-box positions of the thyroid hormone receptor function to
      discriminate between half-sites that differ in sequence at the third and fourth
      base pairs.

PMID- 7622519
TI  - Relationship between P-box amino acid sequence and DNA binding specificity of the
      thyroid hormone receptor. The effects of sequences flanking half-sites in thyroid
      hormone response elements.
AB  - The three P-box amino acids in the DNA recognition alpha-helix of steroid/thyroid
      hormone receptors participate in the discrimination of the central base pairs of
      the hexameric half-sites of receptor response elements in DNA. Using a series of
      variant receptors incorporating all 19 possible substitutions for each individual
      P-box amino acid of the human thyroid hormone receptor (hT3R beta), we
      demonstrated that the first P-box position must have a glutamate, and the second
      P-box position must have either an alanine or a glycine for high affinity binding
      to everted repeat elements with half-site sequences of AGGNCA. In the present
      study, the influence of half-site flanking sequence on the compatibility of P-box
      amino acids in hT3R beta with DNA binding was investigated. When a 5' sequence of
      CTG flanked AGGNCA half-sites in an everted repeat, several additional P-box
      variant receptors were able to bind to the DNA that were not able to bind when
      the half-sites were flanked with the 5' sequence CAG. Flanking sequence had the
      most dramatic effects on amino acid substitutions at the first P-box position,
      with smaller effects observed at the second P-box position and only subtle
      effects observed at the third P-box position. Expansion of the number of P-box
      sequences compatible with binding of hT3R beta to thyroid hormone response
      elements required the thymidine in the CTG flanking sequence, an everted repeat
      of the AGGNCA half-sites, and an intermolecular interaction in the C terminus of
      the receptor.

PMID- 7622520
TI  - Interaction of focal adhesion kinase with cytoskeletal protein talin.
AB  - The interaction of cells with extracellular matrix proteins plays a critical role
      in a variety of biological processes. Recent studies suggest that cell-matrix
      interactions mediated by integrins can transduce biochemical signals to the cell
      interior that regulate cell proliferation and differentiation. These studies have
      placed the focal adhesion kinase (FAK), an intracellular protein tyrosine kinase,
      in a central position in integrin-initiated signal transduction pathways
      (Zachary, I., and Rozengurt, E. (1992) Cell 71, 891-894; Schaller, M., and
      Parsons, J. T. (1993) Trends Cell Biol. 3, 258-262). Here, we report data
      suggesting a possible association of FAK with the cytoskeletal protein talin in
      NIH 3T3 cells. We have identified a 48-amino acid sequence in the carboxyl
      terminal domain of FAK necessary for talin binding in vitro. Furthermore, we have
      correlated the ability of integrin to induce FAK phosphorylation with its ability
      to bind talin using a mutant integrin lacking the carboxyl-terminal 13 amino
      acids. These studies suggest talin may be a mediator for FAK activation in
      signaling initiated by integrins and may provide an explanation for the
      dependence on the integrity of actin-cytoskeleton of multiple intracellular
      signaling pathways converging to FAK activation and autophosphorylation.

PMID- 7622521
TI  - Mutational analysis of the pleckstrin homology domain of the beta-adrenergic
      receptor kinase. Differential effects on G beta gamma and phosphatidylinositol
      4,5-bisphosphate binding.
AB  - The beta gamma subunits of heterotrimeric G proteins (G beta gamma) play a
      variety of roles in cellular signaling, one of which is membrane targeting of the
      beta-adrenergic receptor kinase (beta ARK). This is accomplished via a physical
      interaction of G beta gamma and a domain within the carboxyl terminus of beta ARK
      which overlaps with a pleckstrin homology (PH) domain. The PH domain of beta ARK
      not only binds G beta gamma but also interacts with phosphatidylinositol 4,5
      bisphosphate (PIP2). Based on previous mapping of the G beta gamma binding region
      of beta ARK, and conserved residues within the PH domain, we have constructed a
      series of mutants in the carboxyl terminus of beta ARK in order to determine
      important residues involved in G beta gamma and PIP2 binding. To examine the
      effects of mutations on G beta gamma binding, we employed three different
      methodologies: direct G beta gamma binding to GST fusion proteins; the ability of
      GST fusion proteins to inhibit G beta gamma-mediated beta ARK translocation to
      rhodopsin-enriched rod outer segments; and the ability of mutant peptides
      expressed in cells to inhibit G beta gamma-mediated inositol phosphate
      accumulation. Direct PIP2 binding was also assessed on mutant GST fusion
      proteins. Ala residue insertion following Trp643 completely abolished the ability
      of beta ARK to bind G beta gamma, suggesting that a proper alpha-helical
      conformation is necessary for the G beta gamma.beta ARK interaction. In contrast,
      this insertional mutation had no effect on PIP2 binding. Both G beta gamma
      binding and PIP2 binding were abolished following Ala replacement of Trp643,
      suggesting that this conserved residue within the last subdomain of the PH domain
      is crucial for both interactions. Other mutations also produced differential
      effects on the physical interactions of the beta ARK carboxyl terminus with G
      beta gamma and PIP2. These results suggest that the last PH subdomain and its
      neighboring sequences within the carboxyl terminus of beta ARK, including Trp643,
      Leu647, and residues Lys663-Arg669, are critical for G beta gamma binding while
      Trp643 and residues Asp635-Glu639 are important for the PH domain to form the
      correct structure for binding to PIP2.

PMID- 7622522
TI  - Heat shock-sensitive expression of calreticulin. In vitro and in vivo up
      regulation.
AB  - Calreticulin (CRT) is an ubiquitous, highly conserved, Ca(2+)-binding protein of
      the sarcoplasmic and endoplasmic reticulum. The precise function(s) of CRT is
      unknown. However, based on sequence analyses and observations that it may bind to
      steroid receptors and integrins and store Ca2+ within the cell, it has been
      postulated to play a "housekeeping" role. To determine whether the level of
      expression of CRT is affected by stress, we examined the heat shock response of
      CRT from a variety of cultured cells, including vascular endothelial, lung
      epithelial, and lung fibroblasts. Following exposure of the cells to 42 degrees
      C, CRT mRNA transiently accumulated 2.5-4.2-fold at 1-6 h. Nuclear run-on studies
      and mRNA stability experiments confirmed that the predominant mechanism of
      augmentation was transcriptional. Chloramphenicol acetyltransferase assays
      further indicated that the promoter region, containing a putative heat shock
      element between -172 and -158 of the human CRT gene, is heat shock-sensitive.
      Finally, we demonstrated the in vivo significance of these findings by exposing
      rats to hyperthermia. This resulted in accumulation of CRT mRNA and an
      augmentation of CRT protein in lung tissue. We hypothesize that this stress
      induced up-regulation of CRT contributes to the mechanism(s) by which the
      vascular endothelium and lung tissue, and possibly other organ systems, maintain
      homeostasis when exposed to a variety of pathophysiological conditions.

PMID- 7622523
TI  - Conformational changes monitored on the glutamate transporter GLT-1 indicate the
      existence of two neurotransmitter-bound states.
AB  - Membrane vesicles from rat brain have been subjected to trypsin treatment in the
      absence and presence of substrates of the (Na+ + K+)-coupled L-glutamate
      transporter GLT-1. The fragments of this transporter have been detected upon
      immunoblotting employing several antibodies raised against sequences from this
      transporter. At the amino terminus, initially a fragment of an apparent molecular
      mass of 30 kDa is generated. This fragment is subsequently cleaved to one of 16
      kDa. The generation of these bands is greatly inhibited in the presence of
      lithium. Moreover, lithium abolishes the positive cooperative activation of the
      transporter by sodium. The generation of the 30- and 16-kDa fragments is
      accelerated in the presence of L-glutamate and other transportable analogues,
      provided sodium is present as well. The 30-kDa fragment also contains an epitope
      from the loop connecting the putative membrane-spanning alpha-helices 3 and 4.
      This epitope, in contrast with the amino-terminal one, is destroyed with time.
      The carboxyl-terminal epitope is predominantly located on a 43-kDa fragment which
      is slowly converted to one of 35 kDa. This conversion is not inhibited by
      lithium. It is, however, stimulated by L-glutamate and other transportable
      analogues, but only in sodium-containing media. Potassium also stimulates this
      conversion regardless of the presence of L-glutamate. The stimulation of
      generation of amino- and carboxyl-terminal fragments by L-glutamate is not
      mimicked by the nontransportable analogue dihydrokainate. However, the analogue
      blocks the stimulation exerted by L-glutamate. In addition to new experimental
      information on the transporters topology, our observations provide novel
      information on the function of the GLT-1 transporter. Although lithium by itself
      does not sustain transport, it may occupy one of the sodium sites and be
      transported. Furthermore, the transporter-glutamate complex appears to exist in
      at least two states. After the initial binding (suggested to be important for the
      decay of synaptic glutamate), it undergoes a conformational change which
      represents, or is tightly associated with, the transport step.

PMID- 7622524
TI  - Disassembly and reassembly of the yeast vacuolar H(+)-ATPase in vivo.
AB  - The vacuolar H(+)-ATPase of the yeast Saccharomyces cerevisiae is composed of a
      complex of peripheral subunits (the V1 sector) attached to an integral membrane
      complex (the V0 sector). In the experiments described here, attachment of the V1
      to the V0 sector was assessed in wild-type cells under a variety of growth
      conditions. Depriving the yeast cells of glucose, even for as little as 5 min,
      caused dissociation of approximately 70% of the assembled enzyme complexes into
      separate V1 and V0 subcomplexes. Restoration of glucose induced rapid and
      efficient reassembly of the enzyme from the previously synthesized subcomplexes.
      Indirect immunofluorescence microscopy and subcellular fractionation revealed
      detachment of the peripheral subunits from the vacuolar membrane in the absence
      of glucose, followed by reattachment in the presence of glucose. Rapid
      dissociation of vacuolar H(+)-ATPases could also be triggered by shifting cells
      into a variety of other carbon sources, and reassembly could be generated by
      addition of glucose. Disassembly and reassembly of vacuolar H(+)-ATPases in vivo
      may be a means of regulating organelle acidification in response to extracellular
      conditions, or a mechanism for assembling alternate complexes of vacuolar H(+)
      ATPases in different intracellular compartments.

PMID- 7622525
TI  - Mosquito carboxylesterase Est alpha 2(1) (A2). Cloning and sequence of the full
      length cDNA for a major insecticide resistance gene worldwide in the mosquito
      Culex quinquefasciatus.
AB  - Organophosphorus insecticide resistance in Culex mosquitoes is commonly caused by
      increased activity of one or more esterases. The commonest phenotype involves
      elevation of the esterases Est alpha 2 (A2) and Est beta 2 (B2). A cDNA encoding
      the Est alpha 2 esterase has now been isolated from a Sri Lankan insecticide
      resistant mosquito (Culex quinquefasciatus, Say) expression library. In line with
      a recently suggested nomenclature system (Karunaratne, S. H. P. P. (1994)
      Characterization of Multiple Variants of Carboxylesterases Which Are Involved in
      Insecticide Resistance in the Mosquito Culex quinquefasciatus. Ph.D. thesis,
      University of London), as the first sequenced variant of this esterase, it is now
      referred to as Est alpha 2(1). The full-length cDNA of est alpha 2(1) codes for a
      540-amino acid protein, which has high homology with other esterases and lipases
      and belongs to the serine or B-esterase enzyme family. The predicted secondary
      structure of Est alpha 2(1) is similar to the consensus secondary structure of
      proteins within the esterase/lipase family where the secondary and tertiary
      structures have been resolved. The level of identity (approximately 47% at the
      amino acid level) between the est alpha 2(1) and the various Culex est beta (B1
      and B2) cDNA alleles that have been cloned and sequenced suggests that the two
      esterase loci are closely related and arose originally from duplication of a
      common ancestral gene. The lack of a distinct hydrophobic signal sequence for Est
      alpha 2(1) and two possible N-linked glycosylation sites, both situated close to
      the active site serine, suggest that it is a nonglycosylated protein that is not
      exported from the cell. Southern and dot blot analysis of genomic DNA from
      various insecticide-resistant and susceptible mosquito strains show that the est
      alpha 2(1) gene, like est beta 2(1), is amplified in resistant strains. The
      restriction fragment length polymorphism patterns, after probing Southern blots
      of EcoRI-digested genomic DNA with esta alpha 2(1) cDNA, show that the amplified
      and nonamplified est alpha alleles differ in the resistant and susceptible Sri
      Lankan mosquitoes.

PMID- 7622526
TI  - Nitric oxide inhibits macrophage-colony stimulating factor gene transcription in
      vascular endothelial cells.
AB  - Macrophage-colony stimulating factor (M-CSF) contributes to atherogenesis by
      regulating macrophage-derived foam cells in atherosclerotic lesions. Here we
      report that nitric oxide (NO) inhibits the expression of M-CSF in human vascular
      endothelial cells independent of guanylyl cyclase activation. The induction of M
      CSF mRNA expression by either oxidized low density lipoprotein (ox-LDL) or tumor
      necrosis factor-alpha (TNF alpha) was attenuated by NO donors, S
      nitrosoglutathione (GSNO), sodium nitroprusside (SNP), and 3
      morpholinosydnonimine, but not by cGMP analogues, glutathione, or nitrite.
      Inhibition of endogenous NO production by N-monomethyl-L-arginine (L-NMA) also
      increased M-CSF expression in control and TNF alpha-stimulated cells. Nuclear run
      on assays and transfection studies using M-CSF promoter constructs linked to
      chloramphenicol acetyltransferase reporter gene indicated that NO repressed M-CSF
      gene transcription through nuclear factor-kappa B (NF-kappa B). Electrophoretic
      mobility shift assays demonstrated that activation of NF-kappa B by L-NMA, ox
      LDL, and TNF alpha was attenuated by GSNO and SNP, but not by glutathione or cGMP
      analogues. Since the induction of M-CSF expression depends upon NF-kappa B
      activation, the ability of NO to inhibit NF-kappa B activation and M-CSF
      expression may contribute to some of NO's antiatherogenic properties.

PMID- 7622527
TI  - Wettability and interfacial interactions in bioceramic-body-liquid systems.
AB  - Wetting experiments, by the sessile drop technique, were carried out at 37
      degrees C in air to determine the surface and interfacial interactions that take
      place in various solid bioceramics based on Al2O3, ZrO2(YPZ), SiO2, and TiO2 in
      contact with water, Ringer solution, artificial synovial fluid, calf serum, human
      plasma, and whole blood (+ EDTA). The surface energy of the liquids was measured
      by the ring method. The calculated values of the energy of interaction (work of
      adhesion) reveal that intermolecular forces act across the solid-liquid
      interfaces. The contribution of the dispersion and polar interactions to the
      surface energy of the polar liquids and the pure or mixed oxides was determined
      assuming that in the system of Mn-steel-liquids only dispersion forces act at the
      interface. It was found that the contribution of the polar interactions to the
      energy of interaction at the solid-liquid interface increases with the glassy
      phase content of the oxide that causes reduction of the measured contact angle.

PMID- 7622528
TI  - Adhesion and cytokine production by monocytes on poly(2-methacryloyloxyethyl
      phosphorylcholine-co-alkyl methacrylate)-coated polymers.
AB  - Human monocytes isolated from peripheral venous blood were assayed for their
      ability to adhere to various polymers. The culture supernatants were also assayed
      for the cytokines, interleukin-1 beta (IL-beta), interleukin-6 (IL-6), and tumor
      necrosis factor-alpha (TNF-alpha). The polymers evaluated for adherence and
      cytokine production included Pellethane, polyethylene and poly[n-butyl
      methacrylate (BMA)] coated with poly[2-methacryloyloxyethyl phosphorylcholine
      (MPC)-co-alkyl methacrylate] copolymers. In some experiments the test polymers
      were adsorbed with fibrinogen or IgG prior to the addition of monocytes. MPC
      copolymer-coated materials inhibited monocyte and macrophage adhesion after 1 and
      8 days of culture relative to corresponding uncoated polymers and tissue culture
      polystyrene (TCPS). The degree of inhibition by coated Pellethane compared to
      uncoated Pellethane was the greatest, while inhibition of adhesion by coated
      poly(BMA) was the least compared to uncoated poly(BMA). However, adhesion was
      significantly decreased on both coated and uncoated poly(BMA) by day 8. While IL
      1 beta, IL-6, and TNF-alpha release was variably influenced by polymer coating,
      release was consistently inhibited relative to TCPS on day 1. However, cytokine
      production was not inhibited compared to corresponding uncoated polymers on day
      1. With or without protein preadsorption, IL-1 beta release was not detectable in
      the supernatants of any polymer on day 8, IL-6 production was diminished on day
      8, and TNF-alpha production was sustained on day 8. Overall, MPC copolymer-coated
      and uncoated poly(BMA) were the least stimulating, while TCPS was the most
      stimulating.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7622529
TI  - Effect of carbon content on the resistance to localized corrosion of as-cast
      cobalt-based alloys in an aqueous chloride solution.
AB  - The effect of carbon content on the resistance to localized corrosion of ASTM
      F75, as-cast cobalt-based alloys, was studied using potentiostatic polarization
      tests in Ringer's solution. Critical pitting potentials were estimated from the
      potentiostatic polarization curves and were found to increase with decreasing
      carbon content. The highest resistance to pitting corrosion observed at low C
      contents was attributed to a greater chemical and microstructural homogeneity in
      the as-cast condition. The results of the investigation led to the conclusion
      that the use of low C content ASTM-F75 as-cast alloys in the manufacture of
      orthopedic implants may result in a lower release rate of corrosion products
      which should improve the "in vivo" performance of the implants.

PMID- 7622531
TI  - Glass wool-H2O2/CoCl2 test system for in vitro evaluation of biodegradative
      stress cracking in polyurethane elastomers.
AB  - Environmental stress cracking (ESC) in polyetherurethanes has been demonstrated
      in animal models. However, duplication of this phenomenon in vitro has been a
      challenge. The glass wool-H2O2/CoCl2 test system was designed to provide
      oxidation components found in vivo, i.e., hydroxyl radical (HO.), molecular
      oxygen (O2), and superoxide (O2-.) required for auto-oxidation of
      polyetherurethanes. The in vitro test is not only reliable in duplicating the
      characteristics of in vivo stress cracking in polyetherurethanes at 37 degrees C,
      but also accelerates ESC as much as seven times. The test results on several
      types of polyurethanes showed that Tecothane 80A was as vulnerable to
      biodegradative stress cracking in vitro as Pellethane 2363-80A, while the new
      generation of polyurethanes, Corethane, demonstrated great resistance against
      stress cracking.

PMID- 7622530
TI  - Bacteria/blood/material interactions. I. Injected and preseeded slime-forming
      Staphylococcus epidermidis in flowing blood with biomaterials.
AB  - Blood-material interactions were studied using in vitro recirculation with human
      blood, slime-forming Staphylococcus epidermidis, and cardiovascular materials.
      Staphylococcus epidermidis, under preseeded or injected conditions, adhered to
      nonsmooth materials and elevated plasma levels of fibrinopeptide A (FpA) and C3a
      in the presence of all materials. Increased white blood cell (WBC) and platelet
      adhesion and thrombospondin and platelet factor 4 (PF4) release were noted for
      respective materials in the presence of injected bacteria. Materials that adhered
      significant quantities of injected S. epidermidis exhibited low levels of
      adsorbed proteins. Materials with high levels of preseeded S. epidermidis showed
      high levels of adsorbed proteins. Adhesion of preseeded bacteria and blood plasma
      elevations of C3a and FpA were lowest on semicrystalline polymer substrates,
      intermediate on halogenated substrates, and highest on amorphous substrates. In
      the presence of injected bacteria, WBCs and platelets adhered at earlier
      recirculation times to amorphous substrates than to semicrystalline substrates.

PMID- 7622532
TI  - Mediator interactions in macrophage/particulate bone resorption.
AB  - The purpose of this study was to examine the mechanism by which mediators
      released from macrophages exposed to cement particles may interact with cells in
      bone to ultimately lead to bone resorption. Macrophages were exposed to cement
      particles, and then this conditioned medium was exposed to rat calvarial bones in
      vitro. The macrophage conditioned medium contained increased levels of tumor
      necrosis factor, but not interleukin 1 or prostaglandin E2. Exposure of this
      medium to the calvaria led to release of prostaglandin E2 by the calvaria, but
      not tumor necrosis factor or interleukin 1. Bone resorption was assessed by
      measuring the release of calcium 45 from the newborn rat calvarial bones. At 48,
      72, and 96 h of incubation, the macrophage/cement particle-conditioned medium led
      to the release of both prostaglandin E2 and calcium 45 from the calvaria. To
      determine whether the release of calcium 45 was dependent on prostaglandin E2
      production by the cells in bone, the calvaria were incubated with 600 ng/ml of
      indomethacin in addition to the macrophage-conditioned medium. The addition of
      indomethacin was effective in inhibiting both prostaglandin E2 and calcium 45
      release from the calvaria, even after 96 h of exposure to the macrophage
      conditioned medium. This study suggests that tumor necrosis factor produced in
      association with macrophage/cement particle osteolysis arises from macrophages
      and not cells in bone, and that prostaglandin E2 originates from cells in bone
      and not from macrophages. Interleukin 1 was not found to be produced by
      macrophages or bone, and appears to have a lesser role.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7622533
TI  - Adhesion of Staphylococcus epidermidis to biomedical polymers: contributions of
      surface thermodynamics and hemodynamic shear conditions.
AB  - Adhesion studies of Staphylococcus epidermidis RP62A were conducted using a
      rotating disk system to determine the roles of surface physicochemistry and
      topographies under physiologic shear conditions. Six materials were investigated:
      biomedical reference polyethylene and polydimethylsiloxane; argon plasma-treated
      reference polyethylene (Ar-PE); Silastic; expanded polytetrafluoroethylene; and
      woven Dacron. All of the polymers except Dacron demonstrated reduced bacterial
      adhesion with increasing shear stress. Argon plasma treatment of polyethylene
      reduced the level of staphylococcal adhesion. Adsorption of human plasma proteins
      effected significantly lower numbers of adherent bacteria. The lowest adhesion
      was observed for Ar-PE in 1% human plasma protein solution, whereas Dacron had
      the highest number of adherent bacteria. The high adhesion on Dacron was
      attributed to increased bacterial flux caused by topography-induced turbulent
      flow and physical entrapment of the bacteria in the fiber interstices. The
      results indicate that the driving force for S. epidermidis adhesion is strongly
      influenced by substrate physicochemistry, but this may be dominated by physical
      forces such as shear and turbulence.

PMID- 7622534
TI  - Creep characteristics of hand- and vacuum-mixed acrylic bone cement at elevated
      stress levels.
AB  - Compressive creep testing of cylindrical specimens machined from two commercial
      self-polymerizing acrylic bone cements demonstrated measurable creep strains with
      higher creep strains for the hand-mixed cement specimens compared to vacuum-mixed
      cement ones. The average creep strains of hand-mixed cement, after 6 h of
      constant load, ranged from 0.11% at 10.5 MPa to 14.0% at 50 MPa of applied
      stress. Vacuum mixing reduced the average creep strain to 6.7% after 6 h of
      applied stress at 50 MPa. There were no significant differences in the creep
      response between the two types of acrylic cements. The difference in creep
      resistance of the two cements was reduced after vacuum mixing (P = .013), which
      also significantly reduced the cement's internal porosity.

PMID- 7622535
TI  - Characterization of nodules induced by bioactive glass on cultured periodontal
      ligament fibroblasts.
AB  - We previously reported that materials leached from bioactive glass (BG) and
      vitamin D3 induced the formation of nodules on cultured periodontal-ligament
      fibroblasts (PLF). In this study, we have investigated the relationship between
      the conditions of the materials and nodule formation, analyzed morphologically,
      and also studied whether the production of nodules was specific to cultured PLF.
      PLF and skin fibroblasts were cultured in the presence or absence of BG. The
      amounts of calcium, phosphate, sodium and silicon in the culture medium and the
      number of nodules were measured at the 55th day. The nodules were observed
      microscopically and analyzed using an X-ray microanalyzer. In PLF, nodules were
      formed regardless of the presence or absence of BG; however, they were more
      numerous in the presence of BG. In skin fibroblasts, nodules were not observed.
      The amounts of calcium and silicon were higher in the presence of BG, while the
      amount of phosphate was lower. The nodules appeared crystalline with a spongy
      structure and contained calcium and phosphorus. Our results show that the nodules
      were associated with PLF and precipitated by the materials (higher concentrations
      of calcium and silicon), and they were spongy crystal composed of calcium and
      phosphorus.

PMID- 7622536
TI  - Effect of parallel surface microgrooves and surface energy on cell growth.
AB  - To evaluate the effect of surface treatment and surface microtexture on cellular
      behavior, smooth and microtextured silicone substrata were produced. The
      microtextured substrata possessed parallel surface grooves with a width and
      spacing of 2.0 (SilD02), 5.0 (SilD05), and 10 microns (SilD10). The groove depth
      was approximately 0.5 microns. Subsequently, these substrata were either left
      untreated (NT) or treated by ultraviolet irradiation (UV), radiofrequency glow
      discharge treatment (RFGD), or both (UVRFGD). After characterization of the
      substrata, rat dermal fibroblasts (RDF) were cultured on the UV, RFGD, and UVRFGD
      treated surfaces for 1, 3, 5, and 7 days. Comparison between the NT and UV
      substrata revealed that UV treatment did not influence the contact angles and
      surface energies of surfaces with a similar surface topography. However, the
      contact angles of the RFGD and UVRFGD substrata were significantly smaller than
      those of the UV and NT substrata. The dimension of the surface microevents did
      not influence the wettability characteristics. Cell culture experiments revealed
      that RDF cell growth on UV-treated surfaces was lower than on the RFGD and UVRFGD
      substrata. SEM examination demonstrated that the parallel surface grooves on the
      SilD02 and SilD05 substrata were able to induce stronger cell orientation and
      alignment than the events on SilD10 surfaces. By combining all of our findings,
      the most important conclusion was that physicochemical parameters such as
      wettability and surface free energy influence cell growth but play no measurable
      role in the shape and orientation of cells on microtextured surfaces.

PMID- 7622538
TI  - Cranial bone apposition and ingrowth in a porous nickel-titanium implant.
AB  - A 5 x 5 x 1-mm uncoated porous nickel-titanium (nitinol) implant was placed 4 mm
      to either side of the midsection of the frontal bone and 4 mm anterior to the
      coronal suture of the cranial bone of New Zealand White rabbits. In the other
      frontal location, a 5 x 5 x 1-mm coralline hydroxyapatite (HA) (Interpore 200, a
      well-known craniofacial implant material) implant was fitted. Rabbits were killed
      at each of three postsurgical intervals (2, 6, and 12 weeks), and the implants
      were evaluated for gross biocompatibility, bony contact, and ingrowth. No
      adjacent macrophage cells were observed for either implant type, and overlaying
      soft tissues and connective tissues readily adhered to the implants even after 2
      weeks. Both materials made bone contact with the surrounding cranial hard tissue,
      and percent ingrowth increased with surgical recovery time. Measurements of
      microhardness and bone histologic parameters indicated that bone in contact with
      and grown into the implants was similar in properties to the surrounding cranial
      bone. Porous nitinol implants therefore appear to allow for significant cranial
      bone ingrowth after as few as 12 weeks, and thus nitinol appears to be suitable
      for craniofacial applications. Compared to HA, the nitinol implants demonstrated
      a trend for less total apposition and more total ingrowth after 6 and 12 weeks of
      implantation.

PMID- 7622537
TI  - Metabolic response of granulocytes and platelets to synthetic vascular grafts:
      preliminary results with an in vitro technique.
AB  - The metabolism of granulocytes as well as platelets evoked by incubation with
      different synthetic vascular grafts was monitored during 6-h batch experiments
      using microcalorimetry. Standard knitted Dacron grafts, ePTFE-grafts, knitted
      Dacron grafts with collagen impregnation, and knitted Dacron grafts with external
      collagen-coating were used. The heat production per cell was calculated. A rapid
      increase of metabolic activity followed by a gradual decrease was demonstrated
      with both granulocyte suspension and platelet concentrate. Significant
      differences were obtained between the materials with a maximum response of Dacron
      grafts with collagen impregnation for both granulocyte and platelet response. The
      materials had different surface morphologies regarding cell adhesion after
      incubation as demonstrated with scanning electron microscopy with more pronounced
      adhesion on the collagen-impregnated grafts. The results suggest that
      microcalorimetry may be useful for the evaluation of cellular reactions on
      different biomaterials. However, further studies have to reveal the specificity
      of the reactions.

PMID- 7622539
TI  - Surface and blood-contacting properties of alkylsiloxane monolayers supported on
      silicone rubber.
AB  - Self-assembled monolayers of alkylsiloxanes supported on polydimethyl siloxane
      (PDMS) rubber were used as model systems to study the relation between blood
      compatibility and surface chemistry. The inner lumen of PDMS tubes was first
      treated with an oxygen plasma. The resultant oxidized surfaces were
      postderivatized by reacting them with alkyltrichlorosilanes to form the monolayer
      films. The chemical properties of the monolayers were controlled by varying the
      head-group chemical compositions. Surface derivatization was verified using
      variable-angle X-ray photoelectron spectroscopy (XPS or ESCA). Blood
      compatibility was evaluated using a canine ex vivo arteriovenous series shunt
      model. Surfaces grafted with hydrophobic head-groups as -CH3 and -CF3 had
      significantly lower platelet and fibrinogen deposition than the surfaces composed
      of hydrophilic groups such as -CO2CH3, -(CH2CH2O)3COCH3, and -(OCH2CH2)3OH.

PMID- 7622540
TI  - Bioactive bone cement: the effect of amounts of glass powder and histologic
      changes with time.
AB  - A study was conducted to examine the influence of the amount of glass powder
      added to a bioactive bone cement of our formula on its mechanical and biologic
      properties. Serial changes in the cement with time were also examined. The
      bioactive bone cement consisted of CaO-SiO2-P2O5-CaF2 glass powder and bisphenol
      a-glycidyl methacrylate resin. Glass powder was added to the cement in 30, 50,
      70, and 80% weight ratios. The compressive strengths of the resulting cements
      (171-239 MPa) were more than double that of polymethylmethacrylate cement (68
      MPa). Histologic examination of rat tibiae bearing artificial defects packed with
      each bioactive cement showed direct bone contact 4 weeks after surgery. The
      cement with a higher percentage of glass powder showed better direct formation of
      bone around its periphery with a thicker reactive layer. Under scanning electron
      microscopic observation, the reactive layer showed increased levels of calcium
      and phosphorus. Examination of histologic changes up to 26 weeks showed
      progressive bone formation around the cement and no sign of biodegradation.

PMID- 7622541
TI  - Preservation of surface-dependent properties of viral antigens following
      immobilization on particulate ceramic delivery vehicles.
AB  - B-cell stimulation for the purpose of evoking an effective neutralizing humoral
      immune response is a surface phenomenon that is exquisitely specific to antigen
      conformation. Consequently, successful delivery of antigen, such as would be
      desired in a vaccine, entails preservation of an antigen's apparent native
      surface (conformational) properties. Prior to testing the actual vaccinating
      efficacy of delivered antigens, the surface properties could be assessed through
      a variety of in vitro and in vivo assays in which the measurement standard would
      be the properties of the antigens in their native state (whole virus). Using
      surface modified nanocrystalline carbon and calcium-phosphate ceramic
      particulates (carbon ceramics and brushite), we evaluated the surface activity of
      immobilized non-nuclear material extracted from HIV-1. Physical characterization
      showed that the particles with immobilized antigen ("HIV decoys") measured 50 nm
      in diameter (HIV = 50-100 nm) and exhibited the same zeta potentials as whole
      (live) HIV. In vitro testing showed that the HIV decoys were recognized by both
      conformationally nonspecific and specific monoclonal antibodies, were recognized
      by human IgG from HIV antibody-positive patients, and could promote surface
      agglomeration among malignant T-cells similar to live HIV. Last, in vivo testing
      in three vaccinated animal species showed that the HIV decoys elicited humoral
      and cellular immune responses similar to that evoked by whole (live) HIV.

PMID- 7622542
TI  - Dynamic creep behavior of acrylic bone cement.
AB  - Recent studies concerning the fixation of cemented total hip arthroplasty (THA)
      have led to new hypotheses about the dynamic, long-term failure mechanisms
      leading to prosthetic loosening. As a result, the long-term mechanical behavior
      of acrylic bone cement has gained more interest since little is known about these
      properties. In this study, the dynamic, compressive creep deformation of acrylic
      bone cement was examined. An amount of creep was found, with creep strains
      exceeding the elastic strain during 14 x 10(6) loading cycles. There was a linear
      relationship between the logarithmic values of the number of loading cycles and
      the creep strain. The effect of stress level on the amount of creep was different
      from that in results of static experiments reported in the literature. Comparing
      the results with tensile creep experiments revealed that bone cement under a
      tensile load creeps much quicker than under a compressive one. Young's modulus
      was significantly higher when the material was loaded at higher strain rates. The
      bone cement became stiffer with an increasing number of loading cycles. The creep
      behavior of bone cement is important for the long-term behavior of cemented THA.
      It enables subsidence of the stem and attenuation of stress peaks in the cement
      mantle.

PMID- 7622543
TI  - Assessment of viability and proliferation of in vivo silicone-primed lymphocytes
      after in vitro re-exposure to silicone.
AB  - The functional response of peripheral blood lymphocytes isolated from 22 patients
      with silicone gel-filled breast implants was assessed after in vitro re-exposure
      to silicone. Using cell culture test methods to quantify proliferation and
      viability and/or activation of lymphocyte microcultures, i.e., the uptake of
      tritiated thymidine (3H-TdR uptake test) and the reduction of formazan salts (MTT
      assay), interesting data were obtained. Peripheral blood lymphocytes purified
      from patients wearing silicone gel-filled breast implants react in vitro to
      silicone showing a statistically significant increase of both proliferation and
      viability, while healthy subjects do not respond on in vitro exposure to
      silicone. Differences resulted even more statistically significant when patients
      were divided into two groups depending on the type of surgery they underwent:
      patients with breast augmentation for aesthetic reasons seem to have an increased
      responsiveness in vitro to silicone compared to patients who experienced a
      reconstructive surgery of the breast. Although they are still preliminary, being
      referred to a limited population, these results suggest that the lymphocytes of
      patients with silicone gel-filled breast implants could be sensitized in vivo
      toward silicone; the re-exposure of these cells to silicone leads to a higher
      functional response which could be looked for by using quantitative in vitro test
      methods.

PMID- 7622544
TI  - Determination of the mineral phases and structure of the bone-implant interface
      using Raman spectroscopy.
AB  - The bone-implant interface formed in a canine distal femur was examined by means
      of a Raman microprobe using an implant model designed to test calcium phosphate
      surface coatings. By using the 960 cm-1 band of calcium phosphate to characterize
      the interface and adjacent mineral, we obtained spatial and compositional
      information about the attachment of bone to the synthetic calcium phosphate
      coating on a titanium support. The interface between bone and the synthetic
      calcium phosphate is approximately 30-40 microns in width.

PMID- 7622545
TI  - Evaluating the Dialine vascular prosthesis knitted from an alternative source of
      polyester yarns.
AB  - The sudden and unilateral decision by E. I. DuPont de Nemours & Co., Inc., to
      withdraw its polymers for use in implantable devices has presented the medical
      device industry with an immediate and serious challenge to find alternative
      sources of biomaterials. In France, the company Cardial S.A. has already taken
      steps to find an alternative polyester yarn to replace Dacron by developing a new
      arterial prosthesis knitted from polyester yarns supplied by Rhone-Poulenc
      Fibres. This article describes an in vitro and in vivo study of this French
      device, called the Dialine prosthesis, with a view to determining its relative
      performance compared to current American and British prostheses, which rely on
      DuPont's Dacron yarn. In addition to analyses of the morphology and textile
      structure, and measurements of its physical and chemical properties, the Dialine
      graft was implanted as a thoracoabdominal bypass in dogs for periods ranging from
      4 h to 6 months. In addition to our pathologic and histologic observations, we
      cleaned and evaluated the explanted prostheses for in vivo changes in dimensions,
      strength, and crystalline microstructure. The Dialine graft was found to differ
      structurally from other polyester prostheses because it is warp-knitted from a
      mixture of flat and texturized yarns with finer filaments. Its denser structure
      has a lower water permeability, greater flexibility and ease of handling,
      satisfactory strength, and dimensional stability, and it presents different
      textures on its luminal and external surfaces. The in vivo trial demonstrated
      that it has excellent biocompatibility and biostability over 6 months. With no
      thrombi observed on the luminal surface after 3 months, it has a faster rate of
      healing, generates compact external and internal capsules with a thinner
      neointima, and has an overall milder inflammatory response than is normally
      observed with Dacron-based prostheses.

PMID- 7622546
TI  - Effect of nickel-based dental casting alloys on fibroblast metabolism and
      ultrastructural organization.
AB  - Previous cell culture evaluations have shown that nickel-chromium dental alloys
      did not affect cellular viability or morphology. However, nickel-based alloys
      released corrosion products which decreased cellular proliferation. It was
      hypothesized that this decrease was due to an interference of cellular energy
      metabolism by released metal ions. To test this hypothesis, we evaluated the
      effects on cellular energy metabolism, adenosine triphosphate (ATP) levels, and
      cellular ultrastructure by four nickel-based alloys, including high and low
      chromium alloys with and without beryllium additions, in human gingival
      fibroblast cell cultures. Energy metabolism was evaluated by measuring glucose-6
      phosphate dehydrogenase (G-6-PDH) activity. ATP levels were measured with the
      luciferin-luciferase method. Cellular membranes and ultrastructural organization
      were evaluated by scanning and transmission electron microscopy. The results of
      this study showed that metal ions released from all alloys completely inhibited G
      6-PDH activity and reduced cellular ATP levels as compared to controls. The
      reduction in intracellular ATP was greater for the beryllium containing alloys
      than the non-beryllium-containing alloys. However, no morphologic changes in
      cellular membranes or organelles were observed. These results support the
      hypothesis that metal ions released from nickel-based dental casting alloys
      interfere with cellular energy metabolism.

PMID- 7622547
TI  - Role of cyclic plastic deformation in the wear of UHMWPE acetabular cups.
AB  - The mechanisms of wear in ultra-high-molecular-weight polyethylene (UHMWPE)
      acetabular cups were investigated on both laboratory simulator-tested cups and a
      clinically retrieved component. Two different levels of wear process were
      identified: one characterized by the formation and detachment of platelet-like
      flakes from initial machining marks, and the other by the formation of fine
      ripple and fibrils by repeated passes of microscopic asperities on the femoral
      head. Both wear processes could be described by a criterion of critical plastic
      strain. A theoretical model was developed to account for the generation of the
      microscopic wear particles based on such a critical strain criterion. Its
      predictions of the dependence of the UHMWPE wear rate on surface roughness and
      applied load were in excellent agreement with previously published experimental
      correlations.

PMID- 7622548
TI  - Release of hexavalent chromium from corrosion of stainless steel and cobalt
      chromium alloys.
AB  - Experiments were undertaken to determine whether hexavalent chromium was released
      during corrosion of orthopedic implants. Uptake of chromium (Cr) by cells and
      separation using amberlite resin were the methods used to determine that
      hexavalent Cr was present. We used salts of chromium as trivalent chromium
      (chromic chloride) and hexavalent chromium (potassium dichromate) to verify that
      the amberlite separation technique separates hexavalent Cr into the upper phase
      and trivalent Cr into the lower phase. The use of the salts also verified that
      only the hexavalent Cr became red blood cell-associated and that most of this was
      intracellular rather than membrane bound. The use of the amberlite separation
      technique demonstrated that the hexavalent Cr in the red blood cells was rapidly
      reduced to trivalent Cr. Cellular uptake of chromium was documented in red blood
      cells following corrosion of stainless-steel and cobalt-chromium implants in
      vivo, in the red blood cells of patients undergoing total joint revisions, and in
      fibroblasts subjected to products of fretting corrosion of stainless-steel and
      cobalt-chromium implants. Thus, corrosion of implants can lead to the release of
      the biologically active hexavalent chromium into the body. This chromium is
      rapidly reduced to trivalent chromium in cells.

PMID- 7622549
TI  - Contribution of vascular catheter material to the pathogenesis of infection: the
      enhanced risk of silicone in vivo.
AB  - There is currently very little information to suggest that polymer materials used
      to make vascular catheters differ in their risk of infection. A rabbit model of
      subcutaneous Staphylococcus aureus infection was used to determine the relative
      risk of infection associated with silicone, polyurethane, polyvinylchloride, and
      Teflon catheters. Seven days after catheter implantation and inoculation with S.
      aureus, catheters were observed for gross purulence and quantitatively cultured.
      Silicone catheters were found to have a greater risk of grossly apparent
      infection (purulence) and a greater number of organisms removed from catheters by
      quantitative culture than the other three catheter materials (P < .01). The risk
      of infection associated with silicone catheters decreased (P < .05) if the S.
      aureus inoculation was delayed for 2 days or if the catheters were preincubated
      in the subcutaneous space prior to insertion. The histology of the inflammatory
      response around the four catheter materials was evaluated at either 2 or 7 days
      after catheter insertion with or without S. aureus inoculation. Silicone
      catheters had greater associated inflammation (P < .05) with or without S. aureus
      inoculation. These results suggest that silicone catheter materials may have
      unique properties that increase the risk of infection after implantation. Further
      studies should be done to understand the mechanism(s) of these observations.

PMID- 7622550
TI  - Platelet activation by healing ePTFE grafts.
AB  - The purpose of this study was to examine the effect of the in vivo maturing ePTFE
      graft surface on platelet activation. Ten canines were randomized to receive
      either a carotid to infrarenal aorta ePTFE graft or sham operation. Animals were
      sampled at specific time points up to 3 months postoperatively. Whole blood
      platelet aggregometry (arachidonic acid, ADP, and collagen agonists) and ATP
      secretion (in response to arachidonic acid, ADP, collagen, and thrombin) were
      measured. Additionally, complete hematologic analysis and histology were
      performed. With time, graft animals showed significantly more decrease in
      platelet aggregation in response to ADP compared to sham animals (P = .023). The
      total amount of ATP per platelet was not different, as demonstrated by equivalent
      ATP release per platelet in response to thrombin. Over the first week, grafted
      dogs developed a decrease in systemic platelet count of 50% (P < .001) that
      persisted over the 3-month follow-up period. With time, overall regression model
      slopes of graft and sham platelet count data were not statistically different (P
      = .29). Histologically, the grafts demonstrated limited cellular ingrowth at both
      anastomoses, with fibrin matrix along the remainder of the blood-biomaterial
      interface. These data suggest that, similar to Dacron, exposure to an ePTFE
      surface results in significant changes in platelet biology, and these platelet
      ePTFE interactions persist even after the graft has formed a mature pseudointima.
      The pseudointima appears to be the primary determinant of the blood-biomaterial
      interaction.

PMID- 7622551
TI  - Control of contact activation on end-point immobilized heparin: the role of
      antithrombin and the specific antithrombin-binding sequence.
AB  - The uptake and activation of FXII from blood plasma was studied in small-diameter
      polyethylene tubing, surface-modified by end-point immobilization of heparin. Two
      preparations of heparin were used to modify the contact-activating properties of
      the plastic tubing: unfractionated, functionally active heparin and low-affinity
      heparin, lacking the specific antithrombin-binding sequence and virtually devoid
      of anticoagulant activity. The uptakes of FXII on the two heparin surfaces were
      similar. No activated FXII could be demonstrated on the unfractionated heparin
      surface, whereas on the low-affinity heparin surface nearly all FXII underwent
      spontaneous activation. The suppression of FXII activation on the unfractionated
      heparin surface was investigated by using plasma depleted of antithrombin,
      complement C1 esterase inhibitor, or both. The removal of antithrombin resulted
      in extensive activation of FXII, whereas the depletion of C1 esterase inhibitor
      had only a minor effect. Experiments with recalcified plasma showed rapid clot
      formation during exposure to the low-affinity heparin surface. After depletion of
      antithrombin, but not complement C1 esterase inhibitor, the recalcified plasma
      clotted in contact with the unfractionated heparin surface as well. We conclude
      that antithrombin and the antithrombin-binding sequence in the surface
      immobilized heparin are essential for the prevention of surface activation of
      FXII and triggering of the intrinsic coagulation system.

PMID- 7622552
TI  - Hydrogel-based three-dimensional matrix for neural cells.
AB  - The ability to organize cells in three dimensions (3D) is an important component
      of tissue engineering. This study sought to develop an extracellular matrix (ECM)
      equivalent with a physicochemical structure capable of supporting neurite
      extension from primary neural cells in 3D. Rat embryonic day 14 striatal cells
      and chick embryonic day 9 dorsal root ganglia extended neurites in 3D in agarose
      hydrogels in a gel concentration-dependent manner. Primary neural cells did not
      extend neurites above a threshold agarose gel concentration of 1.25% wt/vol. Gel
      characterization by hydraulic permeability studies revealed that the average pore
      radius of a 1.25% agarose gel was 150 mm. Hydraulic permeability studies for
      calculating average gel pore radius and gel morphology studies by environmental
      and scanning electron micrography showed that the average agarose gel por size
      decreased exponentially as the gel concentration increased. It is hypothesized
      that the average gel porosity plays an important role in determining the ability
      of agarose gels to support neurite extension. Lamination of alternating
      nonpermissive, permissive, and nonpermissive gel layers facilitated the creation
      of 3D neural tracts in vitro. This ability of agarose hydrogels to organize,
      support, and direct neurite extension from neural cells may be useful for
      applications such as 3D neural cell culture and nerve regeneration. Agarose
      hydrogel substrates also offer the possibility of manipulating cells in 3D, and
      may be used as 3D templates for tissue engineering efforts in vitro and in vivo.

PMID- 7622553
TI  - [ASCO 1995--highlights on breast and ovarian neoplasms].

PMID- 7622554
TI  - NAC covers ribosome-associated nascent chains thereby forming a protective
      environment for regions of nascent chains just emerging from the peptidyl
      transferase center.
AB  - We demonstrate that nascent polypeptide-associated complex (NAC) is one of the
      first cytosolic factors that newly synthesized nascent chains encounter. When NAC
      is present, nascent chains are segregated from the cytosol until approximately 30
      amino acids in length, a finding consistent with the well-documented protease
      resistance of short ribosome-associated nascent chains. When NAC is removed, the
      normally protected nascent chains are susceptible to proteolysis. Therefore NAC,
      by covering COOH-terminal segments of nascent chains on the ribosome, perhaps
      together with ribosomal proteins, forms a protective environment for regions of
      nascent chains just emerging from the peptidyl transferase center. Since NAC is
      not a core ribosomal protein, the emergence of nascent chains from the ribosome
      may be more dynamic than previously thought.

PMID- 7622555
TI  - Transmembrane movement of a water-soluble analogue of mannosylphosphoryldolichol
      is mediated by an endoplasmic reticulum protein.
AB  - Based on topological studies mannosylphosphoryldolichol (Man-P-Dol) is
      synthesized on the cytoplasmic face of the RER, but functions as a mannosyl donor
      in Glc3Man9GlcNAc2-P-P-dolichol biosynthesis after the mannosyl-phosphoryl
      headgroup diffuses transversely to the luminal compartment. The transport of
      mannosylphosphorylcitronellol (Man-P-Cit), a water-soluble analogue of Man-P-Dol,
      by microsomal vesicles from mouse liver, has been investigated as a potential
      experimental approach to determine if a membrane protein(s) mediates the
      transbilayer movement of Man-P-Dol. For these studies beta-[3H]Man-P-Cit was
      synthesized enzymatically with a partially purified preparation of Man-P
      undecaprenol synthase from Micrococcus luteus. The uptake of the radiolabeled
      water-soluble analogue was found to be (a) time dependent; (b) stereoselective;
      (c) dependent on an intact permeability barrier; (d) saturable; (e) protease
      sensitive; and (f) highest in ER-enriched vesicles relative to Golgi complex
      enriched vesicles and intact mitochondria. Consistent with the involvement of a
      membrane protein, the analogue did not enter synthetic phosphatidylcholine
      liposomes. [3H]Man-P-Cit also was not transported by human erythrocytes. These
      results indicate that the transport of Man-P-Cit by sealed microsomal vesicles
      from mouse liver is mediated by a membrane protein transport system. It is
      possible that the same membrane protein(s) participates in the transbilayer
      movement of Man-P-Dol in the ER.

PMID- 7622556
TI  - Selective reentry of recycling cell surface glycoproteins to the biosynthetic
      pathway in human hepatocarcinoma HepG2 cells.
AB  - Return of cell surface glycoproteins to compartments of the secretory pathway has
      been examined in HepG2 cells comparing return to the trans-Golgi network (TGN),
      the trans/medial- and cis-Golgi. Transport to these sites was studied by example
      of the transferrin receptor (TfR) and the serine peptidase dipeptidylpeptidase IV
      (DPPIV) after labeling these proteins with the N-hydroxysulfosuccinimide ester of
      biotin on the cell surface. This experimental design allowed to distinguish
      between glycoproteins that return to these biosynthetic compartments from the
      cell surface and newly synthesized glycoproteins that pass these compartments
      during biosynthesis en route to the surface. Reentry to the TGN was measured in
      that surface glycoproteins were desialylated with neuraminidase and were
      monitored for resialylation during recycling. Return to the trans-Golgi was
      traced measuring the transfer of [3H]fucose residues to recycling surface
      proteins by fucosyltransferases. To study return to the cis-Golgi, surface
      proteins were metabolically labeled in the presence of the mannosidase I
      inhibitor deoxymannojirimycin (dMM). As a result surface proteins retained N
      glycans of the oligomannosidic type. Return to the site of mannosidase I in the
      medial/cis-Golgi was measured monitoring conversion of these glycans to those of
      the complex type after washout of dMM. Our data demonstrate that DPPIV does
      return from the cell surface not only to the TGN, but also to the trans-Golgi
      thus linking the endocytic to the secretory pathway. In contrast, no reentry to
      sites of mannosidase I could be detected indicating that the early secretory
      pathway is not or is only at insignificant rates accessible to recycling DPPIV.
      In contrast to DPPIV, TfR was very efficiently sorted from endosomes to the cell
      surface and did not return to the TGN or to other biosynthetic compartments in
      detectable amounts, indicating that individual surface proteins are subject to
      different sorting mechanisms or sorting efficiencies during recycling.

PMID- 7622557
TI  - DNM1, a dynamin-related gene, participates in endosomal trafficking in yeast.
AB  - We identified DNM1, a novel dynamin-related gene in Saccharomyces cerevisiae.
      Molecular and genetic mapping showed that DNM1 is the most proximal gene to the
      right of centromere 12, and is predicted to encode a protein of 85 kD, designated
      Dnm1p. The protein exhibits 41% overall identity with full-length dynamin I and
      55% identity with the most highly conserved 400-amino acid GTPase region. Our
      findings show that like mammalian dynamin, Dnm1p participates in endocytosis;
      however, it is unlikely to be a cognate homologue. Cells with a disruption in the
      DNM1 gene showed mating response defects consistent with a delay in receptor
      mediated endocytosis. The half-life of the Ste3p pheromone receptor was increased
      two- to threefold in the dnm1 mutant, demonstrating that Dnm1p participates in
      the constitutive turnover of the receptor. To define the step in the endocytic
      pathway at which Dnm1p acts, we analyzed mutant strains at both early and late
      steps of the process. Initial internalization of epitope-tagged pheromone
      receptor or of labeled pheromone proceeded with wild-type kinetics. However,
      delivery of the internalized receptor to the vacuole was greatly impeded during
      ligand-induced endocytosis. These data suggest that during receptor-mediated
      endocytosis, Dnm1p acts after internalization, but before fusion with the
      vacuole. The dnm1 mutant was not defective for sorting of vacuolar proteins,
      indicating that Dnm1p is not required for transport from the late endosome to the
      vacuole. Therefore, we suggest that Dnm1p participates at a novel step before
      fusion with the late endosome.

PMID- 7622558
TI  - Functional characterization of Ost3p. Loss of the 34-kD subunit of the
      Saccharomyces cerevisiae oligosaccharyltransferase results in biased
      underglycosylation of acceptor substrates.
AB  - Within the lumen of the rough endoplasmic reticulum, oligosaccharyltransferase
      catalyzes the en bloc transfer of a high mannose oligosaccharide moiety from the
      lipid-linked oligosaccharide donor to asparagine acceptor sites in nascent
      polypeptides. The Saccharomyces cerevisiae oligosaccharyltransferase was purified
      as a heteroligomeric complex consisting of six subunits (alpha-zeta) having
      apparent molecular masses of 64 kD (Ost1p), 45 kD (Wbp1p), 34 kD, 30 kD (Swp1p),
      16 kD, and 9 kD. Here we report a structural and functional characterization of
      Ost3p which corresponds to the 34-kD gamma-subunit of the
      oligosaccharyltransferase. Unlike Ost1p, Wbp1p, and Swp1p, expression of Ost3p is
      not essential for viability of yeast. Instead, ost3 null mutant yeast grow at
      wild-type rates on solid or in liquid media irrespective of culture temperature.
      Nonetheless, detergent extracts prepared from ost3 null mutant membranes are
      twofold less active than extracts prepared from wild-type membranes in an in
      vitro oligosaccharyltransferase assay. Furthermore, loss of Ost3p is accompanied
      by significant underglycosylation of soluble and membrane-bound glycoproteins in
      vivo. Compared to the previously characterized ost1-1 mutant in the
      oligosaccharyltransferase, and the alg5 mutant in the oligosaccharide assembly
      pathway, ost3 null mutant yeast appear to be selectively impaired in the
      glycosylation of several membrane glycoproteins. The latter observation suggests
      that Ost3p may enhance oligosaccharide transfer in vivo to a subset of acceptor
      substrates.

PMID- 7622560
TI  - Quantification and localization of phosphorylated myosin I isoforms in
      Acanthamoeba castellanii.
AB  - The actin-activated Mg(2+)-ATPase activities of the three myosin I isoforms in
      Acanthamoeba castellanii are significantly expressed only after phosphorylation
      of a single site in the myosin I heavy chain. Synthetic phosphorylated and
      unphosphorylated peptides corresponding to the phosphorylation site sequences,
      which differ for the three myosin I isoforms, were used to raise isoform-specific
      antibodies that recognized only the phosphorylated myosin I or the total myosin I
      isoform (phosphorylated and unphosphorylated), respectively. With these antisera,
      the amounts of total and phosphorylated isoform were quantified, the
      phosphomyosin I isoforms localized, and the compartmental distribution of the
      phosphomyosin isoforms determined. Myosin IA, which was almost entirely in the
      actin-rich cortex, was 70-100% phosphorylated and particularly enriched under
      phagocytic cups. Myosins IB and IC were predominantly associated with plasma
      membranes and large vacuole membranes, where they were only 10-20%
      phosphorylated, whereas cytoplasmic myosins IB and IC, like cytoplasmic myosin
      IA, were mostly phosphorylated (60-100%). Moreover, phosphomyosin IB was
      concentrated in actively motile regions of the plasma membrane. More than 20-fold
      more phosphomyosin IC and 10-fold more F-actin were associated with the membranes
      of contracting contractile vacuoles (CV) than of filling CVs. As the total amount
      of CV-associated myosin IC remained constant, it must be phosphorylated at the
      start of CV contraction. These data extend previous proposals for the specific
      functions of myosin I isozymes in Acanthamoeba (Baines, I.C., H. Brzeska, and
      E.D. Korn. 1992. J. Cell Biol. 119: 1193-1203): phosphomyosin IA in phagocytosis,
      phosphomyosin IB in phagocytosis and pinocytosis, and phosphomyosin IC in
      contraction of the CV.

PMID- 7622559
TI  - Insulation of a G protein-coupled receptor on the plasmalemmal surface of the
      pancreatic acinar cell.
AB  - Receptor desensitization is a key process for the protection of the cell from
      continuous or repeated exposure to high concentrations of an agonist. Well
      established mechanisms for desensitization of guanine nucleotide-binding protein
      (G protein)-coupled receptors include phosphorylation,
      sequestration/internalization, and down-regulation. In this work, we have
      examined some mechanisms for desensitization of the cholecystokinin (CCK)
      receptor which is native to the pancreatic acinar cell, and have found the
      predominant mechanism to be distinct from these recognized processes. Upon
      fluorescent agonist occupancy of the native receptor, it becomes "insulated" from
      the effects of acid washing and becomes immobilized on the surface of the plasma
      membrane in a time- and temperature-dependent manner. This localization was
      assessed by ultrastructural studies using a colloidal gold conjugate of CCK, and
      lateral mobility of the receptor was assessed using fluorescence recovery after
      photobleaching. Of note, recent application of the same morphologic techniques to
      a CCK receptor-bearing Chinese hamster ovary cell line demonstrated prominent
      internalization via the clathrin-dependent endocytic pathway, as well as entry
      into caveolae (Roettger, B.F., R.U. Rentsch, D. Pinon, E. Holicky, E. Hadac, J.M.
      Larkin, and L.J. Miller, 1995, J. Cell Biol. 128: 1029-1041). These organelles
      are not observed to represent prominent compartments for the same receptor to
      traverse in the acinar cell, although fluorescent insulin is clearly internalized
      in these cells via receptor-mediated endocytosis. In this work, the rate of
      lateral mobility of the CCK receptor is observed to be similar in both cell types
      (1-3 x 10(-10) cm2/s), while the fate of the agonist-occupied receptor is quite
      distinct in each cell. This supports the unique nature of desensitization
      processes which occur in a cell-specific manner. A plasmalemmal site of
      insulation of this important receptor on the pancreatic acinar cell could be
      particularly effective to protect the cell from processes which might initiate
      pancreatitis, while providing for the rapid resensitization of this receptor to
      ensure appropriate pancreatic secretion to aid in nutrient assimilation for the
      organism.

PMID- 7622561
TI  - Expression of light meromyosin in Dictyostelium blocks normal myosin II function.
AB  - The ability of myosin II to form filaments is essential for its function in vivo.
      This property of self association is localized in the light meromyosin (LMM)
      region of the myosin II molecules. To explore this property in more detail within
      the context of living cells, we expressed the LMM portion of the Dictyostelium
      myosin II heavy chain gene in wild-type Dictyostelium cells. We found that the
      LMM protein was expressed at high levels and that it folded properly into alpha
      helical coiled-coiled molecules. The expressed LMM formed large cytoplasmic
      inclusions composed of entangled short filaments surrounded by networks of long
      tubular structures. Importantly, these abnormal structures sequestered the cell's
      native myosin II, completely removing it from its normal cytoplasmic
      distribution. As a result the cells expressing LMM displayed a myosin-null
      phenotype: they failed to undergo cytokinesis and became multinucleate, failed to
      form caps after treatment with Con A, and failed to complete their normal
      developmental cycle. Thus, expression of the LMM fragment in Dictyostelium
      completely abrogates myosin II function in vivo. The dominant-negative character
      of this phenotype holds promise as a general method to disrupt myosin II function
      in many cell types without the necessity of gene targeting.

PMID- 7622562
TI  - Myosin light chain kinase-regulated endothelial cell contraction: the
      relationship between isometric tension, actin polymerization, and myosin
      phosphorylation.
AB  - The phosphorylation of regulatory myosin light chains by the Ca2+/calmodulin
      dependent enzyme myosin light chain kinase (MLCK) has been shown to be essential
      and sufficient for initiation of endothelial cell retraction in saponin
      permeabilized monolayers (Wysolmerski, R. B. and D. Lagunoff. 1990. Proc. Natl.
      Acad. Sci. USA. 87:16-20). We now report the effects of thrombin stimulation on
      human umbilical vein endothelial cell (HUVE) actin, myosin II and the functional
      correlate of the activated actomyosin based contractile system, isometric tension
      development. Using a newly designed isometric tension apparatus, we recorded
      quantitative changes in isometric tension from paired monolayers. Thrombin
      stimulation results in a rapid sustained isometric contraction that increases 2-
      to 2.5-fold within 5 min and remains elevated for at least 60 min. The
      phosphorylatable myosin light chains from HUVE were found to exist as two
      isoforms, differing in their molecular weights and isoelectric points. Resting
      isometric tension is associated with a basal phosphorylation of 0.54 mol PO4/mol
      myosin light chain. After thrombin treatment, phosphorylation rapidly increases
      to 1.61 mol PO4/mol myosin light chain within 60 s and remains elevated for the
      duration of the experiment. Myosin light chain phosphorylation precedes the
      development of isometric tension and maximal phosphorylation is maintained during
      the sustained phase of isometric contraction. Tryptic phosphopeptide maps from
      both control and thrombin-stimulated cultures resolve both monophosphorylated Ser
      19 and diphosphorylated Ser-19/Thr-18 peptides indicative of MLCK activation.
      Changes in the polymerization of actin and association of myosin II correlate
      temporally with the phosphorylation of myosin II and development of isometric
      tension. Activation results in a 57% increase in F-actin content within 90 s and
      90% of the soluble myosin II associates with the reorganizing F-actin.
      Furthermore, the disposition of actin and myosin II undergoes striking
      reorganization. F-actin initially forms a fine network of filaments that fills
      the cytoplasm and then reorganizes into prominent stress fibers. Myosin II
      rapidly forms discrete aggregates associated with the actin network and by 2.5
      min assumes a distinct periodic distribution along the stress fibers.

PMID- 7622563
TI  - F actin bundles in Drosophila bristles. I. Two filament cross-links are involved
      in bundling.
AB  - Transverse sections though Drosophila bristles reveal 7-11 nearly round, plasma
      membrane-associated bundles of actin filaments. These filaments are hexagonally
      packed and in a longitudinal section they show a 12-nm periodicity in both the
      1.1 and 1.0 views. From earlier studies this periodicity is attributable to cross
      links and indicates that the filaments are maximally cross-linked, singed mutants
      also have 7-11 bundles, but the bundles are smaller, flattened, and the filaments
      within the bundles are randomly packed (not hexagonal); no periodicity can be
      detected in longitudinal sections. Another mutant, forked (f36a), also has 7-11
      bundles but even though the bundles are very small, the filaments within them are
      hexagonally packed and display a 12-nm periodicity in longitudinal section. The
      singed-forked double mutant lacks filament bundles. Thus there are at least two
      species of cross-links between adjacent actin filaments. Hints of why two species
      of cross-links are necessary can be gleaned by studying bristle formation.
      Bristles sprout with only microtubules within them. A little later in development
      actin filaments appear. At early stages the filaments in the bundles are randomly
      packed. Later the filaments in the bundles become hexagonally packed and
      maximally cross-linked. We consider that the forked proteins may be necessary
      early in development to tie the filaments together in a bundle so that they can
      be subsequently zippered together by fascin (the singed gene product).

PMID- 7622564
TI  - Analysis of MAP 4 function in living cells using green fluorescent protein (GFP)
      chimeras.
AB  - MAP 4 is a ubiquitous microtubule-associated protein thought to play a role in
      the polymerization and stability of microtubules in interphase and mitotic cells.
      We have analyzed the behavior of protein domains of MAP 4 in vivo using chimeras
      constructed from these polypeptides and the green fluorescent protein (GFP). GFP
      MAP 4 localizes to microtubules; this is confirmed by colocalization of GFP-MAP 4
      with microtubules that have incorporated microinjected rhodamine-tubulin, and by
      loss of localized fluorescence after treatment of cells with anti-microtubule
      agents. Different subdomains of MAP 4 have distinct effects on microtubule
      organization and dynamics. The entire basic domain of MAP 4 reorganizes
      microtubules into bundles and stabilizes these arrays against depolymerization
      with nocodazole. Within the basic domain, the PGGG repeats, which are conserved
      with MAP 2 and tau, have a weak affinity for microtubules and are dispensable for
      microtubule binding, whereas the MAP 4-unique PSP region can function
      independently in binding. The projection domain shows no microtubule
      localization, but does modulate the association of various binding subdomains
      with microtubules. The acidic carboxy terminus of MAP 4 strongly affects the
      microtubule binding characteristics of the other domains, despite constituting
      less than 6% of the protein. These data show that MAP 4 association with
      microtubules is modulated by sequences both within and outside the basic domain.
      Further, our work demonstrates that GFP chimeras will allow an in vivo analysis
      of the effects of MAPs and their variants on microtubule dynamics in real time.

PMID- 7622565
TI  - Schizosaccharomyces pombe cdc4+ gene encodes a novel EF-hand protein essential
      for cytokinesis.
AB  - Schizosaccharomyces pombe cells divide by medial fission. One class of cell
      division mutants (cdc), the late septation mutants, defines four genes: cdc3,
      cdc4, cdc8, and cdc12 (Nurse, P., P. Thuriaux, and K. Nasmyth. 1976. Mol. & Gen.
      Genet. 146:167-178). We have cloned and characterized the cdc4 gene and show that
      the predicted gene product. Cdc4p, is a 141-amino acid polypeptide that is
      similar in sequence to EF-hand proteins including myosin light chains,
      calmodulin, and troponin C. Two temperature-sensitive lethal alleles, cdc4-8 and
      cdc4-31, accumulate multiple nuclei and multiple improper F-actin rings and septa
      but fail to complete cytokinesis. Deletion of cdc4 also results in a lethal
      terminal phenotype characterized by multinucleate, elongated cells that fail to
      complete cytokinesis. Sequence comparisons suggest that Cdc4p may be a member of
      a new class of EF-hand proteins. Cdc4p localizes to a ringlike structure in the
      medial region of cells undergoing cytokinesis. Thus, Cdc4p appears to be an
      essential component of the F-actin contractile ring. We find that Cdc4 protein
      forms a complex with a 200-kD protein which can be cross-linked to UTP, a
      property common to myosin heavy chains. Together these results suggest that Cdc4p
      may be a novel myosin light chain.

PMID- 7622566
TI  - Members of the NAP/SET family of proteins interact specifically with B-type
      cyclins.
AB  - Cyclin-dependent kinase complexes that contain the same catalytic subunit are
      able to induce different events at different times during the cell cycle, but the
      mechanisms by which they do so remain largely unknown. To address this problem,
      we have used affinity chromatography to identify proteins that bind specifically
      to mitotic cyclins, with the goal of finding proteins that interact with mitotic
      cyclins to carry out the events of mitosis. This approach has led to the
      identification of a 60-kD protein called NAP1 that interacts specifically with
      members of the cyclin B family. This interaction has been highly conserved during
      evolution: NAP1 in the Xenopus embryo interacts with cyclins B1 and B2, but not
      with cyclin A, and the S. cerevisiae homolog of NAP1 interacts with Clb2 but not
      with Clb3. Genetic experiments in budding yeast indicate that NAP1 plays an
      important role in the function of Clb2, while biochemical experiments demonstrate
      that purified NAP1 can be phosphorylated by cyclin B/p34cdc2 kinase complexes,
      but not by cyclin A/p34cdc2 kinase complexes. These results suggest that NAP1 is
      a protein involved in the specific functions of cyclin B/p34cdc2 kinase
      complexes. In addition to NAP1, we found a 43-kD protein in Xenopus that is
      homologous to NAP1 and also interacts specifically with B-type cyclins. This
      protein is the Xenopus homolog of the human SET protein, which was previously
      identified as part of a putative oncogenic fusion protein (Von Lindern et al.,
      1992).

PMID- 7622568
TI  - Spindle dynamics and cell cycle regulation of dynein in the budding yeast,
      Saccharomyces cerevisiae.
AB  - We have used time-lapse digital- and video-enhanced differential interference
      contrast (DE-DIC, VE-DIC) microscopy to study the role of dynein in spindle and
      nuclear dynamics in the yeast Saccharomyces cerevisiae. The real-time analysis
      reveals six stages in the spindle cycle. Anaphase B onset appears marked by a
      rapid phase of spindle elongation, simultaneous with nuclear migration into the
      daughter cell. The onset and kinetics of rapid spindle elongation are identical
      in wild type and dynein mutants. In the absence of dynein the nucleus does not
      migrate as close to the neck as in wild-type cells and initial spindle elongation
      is confined primarily to the mother cell. Rapid oscillations of the elongating
      spindle between the mother and bud are observed in wild-type cells, followed by a
      slower growth phase until the spindle reaches its maximal length. This stage is
      protracted in the dynein mutants and devoid of oscillatory motion. Thus dynein is
      required for rapid penetration of the nucleus into the bud and anaphase B spindle
      dynamics. Genetic analysis reveals that in the absence of a functional central
      spindle (ndcl), dynein is essential for chromosome movement into the bud.
      Immunofluorescent localization of dynein-beta-galactosidase fusion proteins
      reveals that dynein is associated with spindle pole bodies and the cell cortex:
      with spindle pole body localization dependent on intact microtubules. A kinetic
      analysis of nuclear movement also revealed that cytokinesis is delayed until
      nuclear translocation is completed, indicative of a surveillance pathway
      monitoring nuclear transit into the bud.

PMID- 7622567
TI  - NAP1 acts with Clb1 to perform mitotic functions and to suppress polar bud growth
      in budding yeast.
AB  - NAP1 is a 60-kD protein that interacts specifically with mitotic cyclins in
      budding yeast and frogs. We have examined the ability of the yeast mitotic cyclin
      Clb2 to function in cells that lack NAP1. Our results demonstrate that Clb2 is
      unable to carry out its full range of functions without NAP1, even though
      Clb2/p34CDC28-associated kinase activity rises to normal levels. In the absence
      of NAP1, Clb2 is unable to efficiently induce mitotic events, and cells undergo a
      prolonged delay at the short spindle stage with normal levels of Clb2/p34CDC28
      kinase activity. NAP1 is also required for the ability of Clb2 to induce the
      switch from polar to isotropic bud growth. As a result, polar bud growth
      continues during mitosis, giving rise to highly elongated cells. Our experiments
      also suggest that NAP1 is required for the ability of the Clb2/p34CDC28 kinase
      complex to amplify its own production, and that NAP1 plays a role in regulation
      of microtubule dynamics during mitosis. Together, these results demonstrate that
      NAP1 is required for the normal function of the activated Clb2/p34CDC28 kinase
      complex, and provide a step towards understanding how cyclin-dependent kinase
      complexes induce specific events during the cell cycle.

PMID- 7622569
TI  - Stimulation of neurite outgrowth in PC12 cells by EGF and KCl depolarization: a
      Ca(2+)-independent phenomenon.
AB  - MAP kinase activity is necessary for growth factor induction of neurite outgrowth
      in PC12 cells. Although NGF and EGF both stimulate MAP kinase activity, EGF does
      not stimulate neurite extension. We report that EGF, in combination with KCl,
      stimulates neurite outgrowth in PC12 cells. This phenomenon was independent of
      intracellular Ca2+ increases and not due to enhancement of MAP kinase activity
      over that seen with EGF alone. However, EGF plus KCl increased intracellular
      cAMP, and other cAMP elevating agents acted synergistically with EGF to promote
      neurite outgrowth. Stimulation of neurite outgrowth by cAMP and EGF was blocked
      by inhibitors of transcription suggesting that synergistic regulation of
      transcription by the cAMP and MAP kinase pathways may stimulate neurite growth.

PMID- 7622572
TI  - Macrophage colony-stimulating factor induces thrombospondin 1 production by
      cultured human macrophages.
AB  - The role of colony-stimulating factors (CSFs) in regulating the synthesis of
      thrombospondin 1 (TSP1) by cultured human macrophages is investigated. Macrophage
      (M)-CSF is shown rapidly and transiently to induce two predominant species of
      TSP1 mRNA. One of these species was 3.2 kb in size and appeared to be specific to
      M-CSF-stimulated macrophages. Adherent M-CSF-treated macrophages are also shown
      to express abundant surface cell-associated TSP rapidly when examined by indirect
      immunofluorescence staining. Granulocyte-macrophage (GM)-CSF induced TSP1 mRNA at
      a later time point, and this was attributable to the effects of endogenous M-CSF
      induced by the GM-CSF; the GM-CSF-treated cells did not display surface
      associated TSP after 3 hr of treatment. Analysis of the TSP1 protein synthesised
      by the M-CSF-treated macrophages revealed the expected trimeric form of the
      molecule. In addition, an unidentified 95-kDa protein was found to be covalently
      associated with immunoreactive TSP1, and this appeared to be specific to the
      macrophages as it was not found in TSP1 precipitated from other cell types. It is
      suggested that the induction of TSP1 by M-CSF may play an important role in the
      major physiological functions of macrophages.

PMID- 7622570
TI  - A phosphatidylinositol 4,5-bisphosphate-sensitive casein kinase I alpha
      associates with synaptic vesicles and phosphorylates a subset of vesicle
      proteins.
AB  - In interphase cells, alpha-casein kinase I (alpha-CKI) is found associated with
      cytosolic vesicular structures, the centrosome, and within the nucleus. To
      identify the specific vesicular structures with which alpha-CKI is associated,
      established cell lines and primary rat neurons were immunofluorescently labeled
      with an antibody raised to alpha-CKI. In nonneuronal cells, alpha-CKI colocalizes
      with vesicular structures which align with microtubules and are partially
      coincident with both Golgi and endoplasmic reticulum markers. In neurons, alpha
      CKI colocalizes with synaptic vesicle markers. When synaptic vesicles were
      purified from rat brain, they were highly enriched in a CKI, based on activity
      and immunoreactivity. The synaptic vesicle-associated CKI is an extrinsic kinase
      and was eluted from synaptic vesicles and purified. This purified CKI has
      properties most similar to alpha-CKI. When the activities of casein kinase I or
      II were specifically inhibited on isolated synaptic vesicles, CKI was shown to
      phosphorylate a specific subset of vesicle proteins, one of which was identified
      as the synaptic vesicle-specific protein SV2. As with alpha-CKI, the synaptic
      vesicle CKI is inhibited by phosphatidylinositol 4,5-bisphosphate (PIP2).
      However, synthesis of PIP2 was detected only in plasma membrane-containing
      fractions. Therefore, PIP2 may spatially regulate CKI. Since PIP2 synthesis is
      required for secretion, this inhibition of CKI may be important for the
      regulation of secretion.

PMID- 7622573
TI  - Transforming growth factor-beta 1 modulates adenylyl cyclase signaling elements
      and epidermal growth factor signaling in cardiomyocytes.
AB  - Studies presented in this report were designed to investigate the effects of
      transforming growth factor-beta 1 (TGF-beta 1) on epidermal growth factor (EGF)
      mediated stimulation of cAMP accumulation in cardiac myocytes and elucidate the
      mechanism(s) involved in this modulation. TGF-beta 1 (20 pM) treatment of cardiac
      myocytes, in a time-dependent manner, decreased the ability of EGF (100 nM) to
      increase cAMP accumulation. Significant attenuation of EGF-elicited cAMP
      accumulation was observed 2 h after exposure to TGF-beta 1 and 18 h after
      addition of TGF-beta 1, the ability of EGF to increase cAMP accumulation was
      completely obliterated. TGF-beta 1 neither decreased immunoprecipitable EGF
      receptors in membranes from cardiomyocytes nor altered the specific binding of
      [125I]EGF to cardiomyocyte membranes. However, TGF-beta 1 decreased the ability
      of EGF to phosphorylate membrane proteins on tyrosine residues. TGF-beta 1
      treatment of cardiomyocytes also decreased the ability of forskolin to augment
      cAMP accumulation in intact cells and stimulate adenylyl cyclase activity.
      Similarly, in membranes of TGF-beta 1-treated cells, neither isoproterenol nor
      EGF stimulated adenylyl cyclase activity. Interestingly, as assessed by the
      ability of A1F4- to stimulate adenylyl cyclase, TGF-beta 1 did not alter the
      coupling between Gs and catalytic subunits. Likewise, TGF-beta 1 did not alter
      the functional activity of the inhibitory regulatory element of the system, Gi.
      Western analysis of cellular proteins revealed that TGF-beta 1 did not alter the
      amounts of Ga alpha, Gi alpha 2, and Gi alpha 3. We conclude that TGF-beta 1
      attenuates EGF-elicited cAMP accumulation in cardiomyocytes, in part, by
      decreasing the EGF receptor kinase function and that TGF-beta 1-mediated
      alterations in the activity of adenylyl cyclase catalytic subunit also contribute
      toward the regulation of adenylyl cyclase by various agonists.

PMID- 7622574
TI  - Repression of the Id2 (inhibitor of differentiation) gene promoter during exit
      from the cell cycle.
AB  - The Id2 gene is one of several "Id-like" genes which encode helix-loop-helix
      proteins which dimerize with basic helix-loop-helix proteins and inhibit binding
      to the DNA enhancer element known as an E box. By repressing the DNA binding
      activity of basic helix-loop-helix proteins, Id proteins inhibit transcription of
      tissue-specific genes in myoblasts, hematopoietic precursor cells, and other
      types of undifferentiated cells. Serum starvation results in the disappearance of
      Id gene transcripts in most types of cultured cells, and often induces
      differentiation of these cells. In order to gain some insight into this process,
      we have analyzed Id2 promoter function in the glioma cell line U87Y. We have
      isolated 300 base pairs of Id2 promoter sequence which is sufficient to repress
      the activity of a reporter gene in serum-starved U87Y cells, but induces the
      activity of the reporter gene when the cells are stimulated with fresh serum. Two
      regions within this 300 base pair sequence contain repressor elements; deletion
      of either region results in increased promoter activity. Both repressor regions
      serve as binding sites for a protein present in extracts from serum-starved U87Y
      cells but not in serum-stimulated cells.

PMID- 7622571
TI  - The chemotactic response to PDGF-BB: evidence of a role for Ras.
AB  - The PDGF receptor-beta mediates both mitogenic and chemotactic responses to PDGF
      BB. Although the role of Ras in tyrosine kinase-mediated mitogenesis has been
      characterized extensively, its role in PDGF-stimulated chemotaxis has not been
      defined. Using cells expressing a dominant-negative ras, we find that Ras
      inhibition suppresses migration toward PDGF-BB. Overexpression of either Ras
      GTPase activating protein (Ras-GAP) or a Ras guanine releasing factor (GRF) also
      inhibited PDGF-stimulated chemotaxis. In addition, cells producing excess
      constitutively active Ras failed to migrate toward PDGF-BB, consistent with the
      observation that either excess ligand or excess signaling intermediate can
      suppress the chemotactic response. These results suggest that Ras can function in
      normal cells to support chemotaxis toward PDGF-BB and that either too little or
      too much Ras activity can abrogate the chemotactic response. In contrast to Ras
      overexpression, cells producing excess constitutively active Raf, a downstream
      effector of Ras, did migrate toward PDGF-BB. Cells expressing dominant-negative
      Ras were able to migrate toward soluble fibronectin demonstrating that these
      cells retained the ability to migrate. These results suggest that Ras is an
      intermediate in PDGF-stimulated chemotaxis but may not be required for
      fibronectin-stimulated cell motility.

PMID- 7622575
TI  - Preferential induction of apoptosis in mouse CD4+CD8+ alpha beta TCRloCD3 epsilon
      lo thymocytes by zinc.
AB  - High concentrations of zinc salts (500 microM and greater) are known to inhibit
      apoptosis in a variety of systems. However, closer examination of dose effects
      revealed that lower concentrations of zinc (80-200 microM) could induce apoptosis
      in approximately 30-40% of mouse thymocytes following 8 h incubation. The ability
      of zinc to cause thymocyte apoptosis was detected flow-cytometrically by
      reduction in propidium iodide DNA fluorescence and forward scatter, both
      quantitative indicators of apoptotic death. Zinc induced both internucleosomal
      DNA fragmentation and morphological changes characteristic of apoptosis as
      determined by gel electrophoresis and electron microscopy, respectively. In
      addition, transcriptional and translational inhibitors prevented zinc-induced
      apoptosis, indicating a requirement for de novo mRNA and protein synthesis,
      another characteristic of apoptotic death. Fluorescent immunophenotype-specific
      apoptotic analysis indicated that zinc-induced apoptosis occurred primarily in
      the less mature CD4+CD8+ alpha beta TCRloCD3 epsilon lo thymocyte subset, with
      lower amounts of death occurring in the other subsets. This lineage specificity
      was shared with glucocorticoid-induced apoptosis. Taken together, these results
      indicate that zinc induces true apopotitic death in mouse thymocytes and suggests
      a role for zinc in the regulation of apoptosis.

PMID- 7622576
TI  - Different regulatory pathways involved in ATP-stimulated chloride secretion in
      rat epididymal epithelium.
AB  - The regulatory pathways involved in the ATP-stimulated Cl- secretion across rat
      epididymal epithelium were investigated by the short-circuit current (ISC)
      technique. Biphasic characteristic was observed in the ISC responded to ATP (0.01
      10 microM). Inhibitor of P1 receptor, 8-phenyltheophylline (up to 100 microM),
      did not have any effect on both phases of the ATP-stimulated ISC. The order of
      potency for stimulation of the two phases in ISC was ATP > ADP >> AMP, adenosine,
      consistent with the presence of P2-purinoceptors. Cl- channel blocker, disulfonic
      acid stilbene (DIDS, 300 microM), only inhibited the first peak of the ATP
      stimulated ISC while diphenylamine-dicarboxylic acid (DPC, 1 mM) reduced both,
      indicating the involvement of different conductance pathways. DIDS was found to
      have an inhibitory effect on Ca(2+)-activated ISC (induced by ionomycin, 10
      microM) but not cAMP-activated ISC (induced by forskolin, 1 microM) which could
      only be blocked by DPC. Both peaks of the ATP-activated ISC could be
      significantly inhibited by pretreatment with a Ca(2+)-chelating agent, BAPTA-AM
      (50 microM). An increase in cellular cAMP content upon stimulation of ATP was
      measured by radioimmunoassay. No significant increase in cAMP production was
      observed in cells stimulated with adenosine. The ATP-induced cAMP increase was
      prevented by pretreatment with BAPTA-AM (100 microM) indicating that cAMP
      production upon ATP stimulation was secondary to an increase in intracellular
      Ca2+ concentration. These results indicate that the ATP-stimulated Cl- secretion
      could be mediated by Ca2+ and cAMP-dependent regulatory pathways giving rise to
      the biphasic nature of the ATP-induced ISC.

PMID- 7622578
TI  - Swelling activates chloride current and increases internal calcium in
      nonpigmented epithelial cells from the rabbit ciliary body.
AB  - Membrane current and [Ca]i in rabbit nonpigmented ciliary body epithelial cells
      (NPE cells) were monitored with combined patch-clamp and fura-2 measurements
      during cell swelling induced by anisosmotic conditions. In the presence of K
      channel blockers, cell swelling produced an increase in membrane current,
      accompanied by an increase in [Ca]i. Structural changes in the cell, associated
      with membrane deformation, may be the cause of the increase in [Ca]i during
      swelling. The conductance activated by swelling was permeable to Cl: it was
      dependent on the Cl concentration gradient across the cell membrane, and it was
      blocked by the Cl-channel blockers DIDS, SITS, NPPB, and DIOA. Although swelling
      increased both Cl current and [Ca]i, there was no evidence that Ca was involved
      in the regulation of the Cl conductance. Cell swelling activated the current even
      when [Ca]i was strongly buffered at an elevated level (500 nM) or at a low level
      (approximately 0) with internal Ca-BAPTA/Cs-BAPTA mixtures. In addition, Cl
      conductance was unaffected when [Ca]i was increased with a Ca ionophore. There
      was also no evidence that cAMP participates in the regulation of the Cl
      conductance: swelling activation of the current occurred in the presence of cAMP
      inhibitor (Rp-cAMP-S) and cAMP mimic (Sp-cAMP-S). The data suggest independent
      involvement of Cl conductance and internal Ca in the regulation of cell volume in
      NPE cells.

PMID- 7622579
TI  - Induction of intercellular adhesion molecule-1 by monocyte adhesion to
      endothelial cells in human culture system.
AB  - Increased monocyte adhesion to the endothelial lining of blood vessels by
      cytokine-inducible adhesion proteins is a crucial event in inflammatory
      processes. Moreover, adherence is known to induce cytokine gene expression,
      suggesting a possible positive feedback mechanism. Therefore, we determined
      whether monocyte adhesion to endothelial cells (ECs) amplifies their adhesion by
      inducing intercellular adhesion molecule 1 (ICAM-1), and whether such positive
      feedback mechanism could be mediated by secretion of interleukin-1 (IL-1). Using
      monocyte-EC couples obtained after monocyte adhesion to ECs, and methods of
      quantitative polymerase chain reaction and immunofluorescence flow cytometry, we
      showed a biphasic increase of ICAM-1 mRNA content (2 and 16 hours) and a time
      dependent increase of cell surface expression of ICAM-1, mainly on ECs, and
      couple adhesiveness, after monocyte adhesion to ECs. Anti-ICAM-1 monoclonal
      antibody inhibited 63% of the enhancement of adhesiveness induced on monocyte-EC
      couples by previous monocyte adhesion, suggesting that monocyte adhesion to ECs
      induces an increase of couple adhesiveness which is partially dependent on the
      ICAM-1 pathway. The early ICAM-1 mRNA induction was associated with a fast
      induction of IL-1 beta mRNA and a 7.7-fold increase in IL-1 beta protein in
      supernatant. However, 30% of this 2-hour ICAM-1 mRNA peak was abolished by
      recombinant soluble human IL-1 receptor, suggesting that the early ICAM-1 over
      expression was partially mediated by IL-1 beta, and could be induced directly by
      adherence. The second ICAM-1 mRNA peak was accompanied by a marked increase in IL
      1 beta mRNA and protein secretion (2.6 ng/ml). The binding to ICAM-1 did not
      appear to directly stimulate IL-1 beta synthesis. These results indicate that
      monocyte adhesion to endothelial cells appears to stimulate their own recruitment
      via induction of ICAM-1 thereby constituting a self-perpetuating positive
      feedback system.

PMID- 7622577
TI  - Developmental changes in phosphorylation of the transcription factor CREB in the
      embryonic murine palate.
AB  - Cyclic AMP, via activation of cAMP-dependent protein kinase (PKA) and subsequent
      protein phosphorylation, regulates a number of cellular and tissue responses that
      are critical to normal development of the mammalian palate. The present study
      examines the expression, distribution, and phosphorylation in the developing
      murine palate of a substrate for PKA known as the cAMP-response element binding
      protein (CREB). This 43 x 10(3) M(r) protein functions as a regulator of cAMP
      inducible gene expression. CREB is expressed constituitively throughout the
      palatal morphogenetic period and is ubiquitously distributed throughout palatal
      tissue. Immunofluorescent staining of palatal cells and tissues with an anti-CREB
      antibody revealed CREB to be localized to cell nuclei. Western blot analysis of
      extracts of staged palatal shelves with an antibody specific for phospho-ser 133
      CREB demonstrated a steady increase in CREB phosphorylation at this residue
      during palate development. These observations show a temporal correlation with
      expression levels of cAMP-regulated genes in palate cells. The data indicate that
      CREB activity in the developing palate is most likely to be regulated at the
      level of protein phosphorylation as opposed to changes in levels of CREB protein
      expression.

PMID- 7622580
TI  - THP-1 macrophage membrane-bound plasmin activity is up-regulated by transforming
      growth factor-beta 1 via increased expression of urokinase and the urokinase
      receptor.
AB  - Receptors for urokinase (uPA) and plasminogen provide a mechanism to direct the
      cellular activation of plasminogen. The regulation of these receptors is
      important for several macrophage functions. In these studies, the effect of
      transforming growth factor-beta 1 (TGF-beta 1) on uPA, uPA receptor, and
      plasminogen receptor expression by human THP-1 macrophage was examined. TGF-beta
      1 induction of uPA expression by THP-1 cells was differentiation dependent.
      Suspension and adherent cultures expressed similar constitutive levels of uPA.
      Exposure of adherent cells to TGF-beta 1 led to a dose- and time-dependent
      increase in uPA activity which was paralleled by an increase in uPA antigen and
      uPA mRNA. In contrast, uPA expression by suspension cultures was unresponsive to
      TGF-beta 1. The differential response exhibited by suspension and adherent THP-1
      cells may reflect differences in their expression of TGF-beta 1 receptors, since
      when assayed by crosslinking techniques, suspension cells primarily expressed a
      65 kDa receptor; whereas, the adherent cells expressed 65 and 100 kDa receptors.
      TGF-beta 1-induced alterations in uPA receptor expression by adherent THP-1 cells
      were examined by quantitating membrane-bound uPA activity. Membrane-bound uPA
      activity increased three-fold when cells were incubated with TGF-beta 1. The
      increase in membrane-uPA activity expressed by TGF-beta 1-treated cells was not
      due to increased uPA receptor occupancy since incubation of either control or TGF
      beta 1 primed cells with exogenous uPA did not lead to an increase in membrane
      bound uPA activity. Furthermore, immunoreactive uPA receptor was increased in TGF
      beta 1-treated cells. Following incubation with plasminogen, membrane-bound
      plasmin activity increased three-fold in TGF-beta 1-treated cells. However, no
      change in immunoreactive membrane-bound plasmin(ogen) was observed. In addition,
      binding of 125I-Lys-plasminogen to THP-1 cells was not affected by TGF-beta 1
      treatment. We conclude that TGF-beta 1 stimulates membrane-bound plasmin
      activity, without affecting plasminogen receptor expression, through the up
      regulation of uPA and the uPA receptor expression.

PMID- 7622581
TI  - Characterization of a signal generated by oxidation of protein thiols that
      activates the heat shock transcription factor.
AB  - The diazenecarbonyl derivative, diamide, was used to produce nonnative protein
      disulfides in Chinese hamster ovary cells in order to characterize the events
      that occur during thiol oxidation-induced denaturation that trigger induction of
      Hsp 70. We limit the term protein denaturation to a process involving a
      conformational rearrangement by which the ordered native structure of a protein
      changes to a more disordered structure. Protein thiol oxidation resulted in
      immediate destabilization of proteins, as assessed by differential scanning
      calorimetry (DSC). The DSC profile indicated both a decrease in the onset
      temperature for detection of denaturation and destabilization of a class of
      proteins with an average transition temperature (Tm) of 60 degrees C. Concomitant
      with destabilization was an increase in proteins associated with isolated nuclei.
      Thiol oxidation also induced heat shock transcription factor (HSF) binding
      activity, however, this was nearly undetectable immediately following diamide
      treatment: maximum activation occurred 3 hr following exposure. In contrast, heat
      shock denatured thermolabile proteins which exhibited a Tm of < or = 48 degrees
      C. Heat shock also resulted in a rapid increase in proteins associated with
      isolated nuclei and produced immediate and maximum activation of HSF binding. The
      accumulation of Hsp and Hsc 70 mRNA following thiol oxidation reflected the delay
      in HSF binding. Acquisition of HSF binding activity occurred immediately if
      diamide-treated cells were subsequently exposed to a heat shock, indicating that
      HSF was not inactivated by the diamide treatment. Ostensibly, the cellular system
      for detecting denatured/abnormal proteins failed to immediately recognize the
      signal generated by thiol oxidation. These results suggest that at least two
      processes are involved in the induction of Hsp 70 by nonnative disulfide bond
      formation: destabilization of protein structure resulting in denaturation and
      recognition of denatured protein.

PMID- 7622582
TI  - Effect of platelet-derived growth factor on DNA synthesis and gene expression in
      bone marrow stromal cells derived from adult and old rats.
AB  - The effects of platelet-derived growth factor (PDGF) on DNA synthesis and mRNA
      expression of osteoblast markers in marrow stromal cells derived from adult (6
      months) and old (24 months) rats were examined. Treatment of stromal cells from
      adult rats with dexamethasone induced the appearance of osteoblast-like cells.
      PDGF partially also inhibited the differentiation of stromal cells induced by
      dexamethasone. In cultures of serum-starved stromal cells, PDGF stimulated [3H]
      thymidine incorporation into DNA in a dose-dependent manner with a maximum
      stimulation of 15-fold at 500 ng/ml. By comparison, insulin-like growth factor
      (IGF-I) has a small effect on [3H]-thymidine incorporation. The effect of PDGF
      and IGF-I on DNA synthesis was additive. Treatment of the confluent stromal cells
      from adult rats with PDGF increased the mRNA level of osteopontin fourfold
      without any significant effect on alkaline phosphatase and type I collagen mRNAs.
      In contrast, dexamethasone stimulated the mRNA expression of alkaline
      phosphatase, type I collagen, and osteopontin 2.1-, 2.3-, and 14-fold,
      respectively. Addition of PDGF to dexamethasone-treated cells failed to induce
      any further increase in osteopontin expression whereas the expression of alkaline
      phosphatase and type I collagen was partially reduced. The expression of
      osteocalcin mRNA was negligible in stromal cells but stimulated several fold by
      dexamethasone and 1,25(OH)2D3. PDGF inhibited drastically the elevation of
      osteocalcin mRNA. In contrast, IGF-I stimulated type I collagen expression 100%
      without any appreciable effect on the expression of osteopontin and alkaline
      phosphatase. The stimulatory effect of PDGF on osteopontin expression was
      augmented by IGF-I. Furthermore, PDGF attenuated the stimulatory effect of IGF-I
      on type I collagen expression. The responses of cultured cells from old rats to
      growth factors were also examined. PDGF or PDGF plus IGF-I increased [3H]
      thymidine incorporation in stromal cells from old rats but to a lesser extent.
      However, PDGF was equally effective in stimulating osteopontin expression in
      cells from both adult and old rats. We concluded that PDGF is a potent mitogen
      but that the response of stromal cells from old rats is impaired. In addition,
      PDGF stimulates osteopontin expression in stromal cells and this effect is not
      age dependent.

PMID- 7622583
TI  - Kinetics of 125I-PDGF binding and down-regulation of PDGF receptor in human
      arterial smooth muscle cell strains during cellular senescence in vitro.
AB  - Platelet-derived growth factor (PDGF) is one of the major mitogens in serum to
      stimulate replication of human smooth muscle cells (SMCs) in culture. Previous
      studies using human fibroblasts failed to demonstrate changes in the receptor
      systems for growth factors during cellular senescence. We investigated the
      kinetics of 125I-PDGF(-BB) binding and down-regulation of the PDGF receptor in
      three human arterial SMC strains during cellular aging. The number of specific
      125I-PDGF binding sites per cell increased slightly at a population doubling
      level (PDL) of 60%-80% of life span and then decreased at the PDL above 90%. The
      number of receptors per cell-surface area decreased with increasing in vitro age.
      The apparent Kd for the 125I-PDGF binding decreased with in vitro senescence. The
      internalization and degradation of 125I-PDGF per receptor were significantly
      reduced in senescent SMCs and the amount of 125I-PDGF that escaped degradation
      and was recycled back to the cell surface was significantly greater in senescent
      SMCs than young cells. Furthermore, down-regulation of the PDGF receptor was
      significantly greater in senescent SMCs than young cells. Immunoblot studies
      demonstrated that changes in beta-subunit of the PDGF receptor accounted for
      those in the studies using 125I-PDGF and that tyrosine phosphorylation of the
      PDGF receptor was significantly greater in young SMCs than aged cells. Our
      results suggest that age-related changes in the receptor systems for PDGF may be
      important contributors to the failure of DNA synthesis in senescent SMCs.

PMID- 7622585
TI  - Comparative studies between freshly isolated and spontaneously immortalized
      bovine granulosa cells: protein secretion, steroid metabolism, and responsiveness
      to growth factors.
AB  - A bovine granulosa cell line (BGC-1) has been obtained by spontaneous
      immortalization of primary cultures. BGC-1 cells have retained some
      characteristics of primary cultures, such as the hormonal regulation of
      fibronectin biosynthesis. In the present study we have compared BGC-1 cells and
      primary cultures of bovine granulosa cells in terms of protein secretion, steroid
      metabolism, and mitogenic responses to growth factors. The pattern of protein
      secretion in BGC-1 cells was qualitatively similar to that of primary cultures.
      The main differences were a higher proportion of fibronectin and the relative
      amounts of several other unidentified proteins. Progesterone levels in BGC-1
      cultures were undetectable. When BGC-1 cells and primary cultures were incubated
      with [3H]-pregnenolone, the former showed a lower conversion rate to
      progesterone. In contrast, the conversion rate of [3H]-progesterone to 5 alpha
      reduced metabolites was markedly increased in BGC-1 cells. We also examined the
      effects of epidermal growth factor (EGF), insulin like growth factor-I (IGF-I),
      and transforming growth factor-beta (TGF-beta) on DNA synthesis under serum-free
      conditions. Both primary cultures and BGC-1 cells exhibited a stimulatory
      response to EGF and IGF-I on [3H]-thymidine incorporation. Neither BGC-1 cells
      nor primary cultures showed a significant response to TGF-beta when added alone.
      However, in the presence of a combination of EGF and IGF-I, TGF-beta displayed an
      inhibitory effect on primary cultures while it stimulated DNA synthesis in BGC-1
      cells even further. The addition of conditioned medium from BGC-1 cells (BGC-1
      CM) stimulated DNA synthesis on primary cultures to a greater extent than the
      addition of conditioned medium from primary cultures. These results suggest that
      BGC-1 cells may be a useful model to study the regulation of granulosa cell
      function during the period previous to the preovulatory stage of follicular
      development. The differential responses of the immortalized cells to growth
      regulators may offer some clues on the mechanisms that control cell proliferation
      in normal tissues.

PMID- 7622584
TI  - Vasculotropin/vascular endothelial growth factor is an autocrine growth factor
      for human retinal pigment epithelial cells cultured in vitro.
AB  - Vasculotropin (VAS), also called vascular endothelial growth factor (VEGF) or
      vascular permeability factor, is a secreted growth factor whose target cell
      specificity has been reported as restricted to vascular endothelium. Its effects
      are mediated by at least two distinct membrane-spanning tyrosine kinase
      receptors, KDR and flt-1; the expression of which also seems restricted to
      vascular endothelium. We describe here that cultured human retinal pigment
      epithelial (HRPE) cells express both KDR and flt-1 receptors, bind VAS/VEGF on
      two high affinity sites (apparent Kd of 9 and 210 pM corresponding to 940 and
      18,800 sites per cell) and proliferate or migrate upon recombinant VAS/VEGF
      addition. HRPE cells also express the mRNA corresponding to the 121 and 165 amino
      acid forms of VAS/VEGF. HRPE cells release in their own culture medium and store
      in their extracellular matrix self-mitogenic and chemoattractant factors
      indistinguishable from 121 and 165 VAS/VEGF isoforms. The autocrine role of
      VAS/VEGF was confirmed by the inhibition of these bioactivities by neutralizing
      specific anti-VAS/VEGF antibodies.

PMID- 7622586
TI  - Heat-induced bFGF gene expression in the absence of heat shock element correlates
      with enhanced AP-1 binding activity.
AB  - Basic fibroblast growth factor (bFGF) has been shown to be a potent mitogen and a
      promoter of angiogenesis. It has been hypothesized that the expression of the
      bFGF gene may be induced by stress of various types. To test that hypothesis, we
      investigated the expression of the bFGF gene during heat treatment in adriamycin
      resistant (MCF-7/ADR) and -sensitive (MCF-7) human breast carcinoma cells. Under
      normal growth conditions, the bFGF mRNA was detected in MCF-7/ADR cells, while it
      was not detectable in MCF-7 cells by Northern blot analysis. During heating at 41
      degrees C, the level of bFGF mRNA increased in MCF-7/ADR cells and the message
      became detectable in the MCF-7 cell line. However, after continuous heating at 41
      degrees C for 24 h, the bFGF mRNA level decreased to control level in MCF-7/ADR
      cells. Interestingly, simultaneous treatment with heat and 60 micrograms/ml H-7
      (1-(isoquinolinylsulfonyl)-2-methylpiperazine, a potent PKC inhibitor) decreased
      the level of bFGF mRNA in MCF-7/ADR cells. These results suggest that a protein
      kinase, likely PKC, is involved in the transcriptional regulation of the heat
      enhanced bFGF gene expression in human breast carcinoma cells. Although no heat
      shock element can be identified in the promoter of the bFGF gene, we observed
      that the AP-1 binding activity to a TPA responsive element (TRE)-like sequence in
      the promoter of bFGF gene was enhanced by heat, as tested by mobility shift
      assay. Antibody developed against the c-Jun and c-Fos proteins inhibited the AP-1
      binding activity to TRE. Therefore, the AP-1 complex appears to be responsible
      for the heat-enhanced binding to the TRE-like motif of the bFGF gene.
      Furthermore, the increased AP-1 binding activity does not require new protein
      synthesis but activation of the preexisting c-Jun proteins.

PMID- 7622587
TI  - Effect of hypoxia and reoxygenation on the formation and release of reactive
      oxygen species by porcine pulmonary artery endothelial cells.
AB  - Endothelial cells are critical targets in both hypoxia- and reoxygenation
      mediated lung injury. Reactive O2 species (ROS) have been implicated in the
      pathogenesis of hypoxic and reoxygenation lung injury, and xanthine
      dehydrogenase/oxidase (XDH/XO) is a major generator of the ROS. Porcine pulmonary
      artery endothelial cells (PAEC) have no detectable XDH/XO. This study was
      undertaken to examine 1) ROS production by hypoxic porcine PAEC and their
      mitochondria and 2) ROS production and injury in reoxygenated PAEC lacking XDH/XO
      activity. Intracellular H2O2 generation and extracellular H2O2 and O2 divided
      release were measured after exposure to normoxia (room air-5% CO2), hypoxia (0%
      O2-95% N-5% CO2), or hypoxia followed by normoxia or hyperoxia (95% O2-5% CO2).
      Exposure to hypoxia results in significant reductions in intracellular H2O2
      formation and extracellular release of H2O2 and O2 by PAEC and mitochondria. The
      reductions occur with as little as a 2 h exposure and progress with continued
      exposure. During reoxygenation, cytotoxicity was not observed, and the production
      of ROS by PAEC and their mitochondria never exceeded levels observed in normoxic
      cells. The absence of XDH/XO may prevent porcine PAEC from developing injury and
      increased ROS production during reoxygenation.

PMID- 7622588
TI  - Selective induction of cell cycle regulatory genes cdk1 (p34cdc2), cyclins A/B,
      and the tumor suppressor gene Rb in transformed cells by okadaic acid.
AB  - Genes encoding cdk1 (p34cdc2), cyclin A, cyclin B, and the tumor suppressor gene
      Rb are fundamental regulators of cell cycle progression which associate as a
      complex with the transcription factor E2F. Expression of many of these proteins
      has previously been shown to be repressed by okadaic acid, a specific inhibitor
      of protein phosphatases 1/2A (PP1/PP2A), resulting in growth arrest in
      nontransformed but immortalized cells. We have investigated levels of mRNA
      encoding cdk1 (p34cdc2), cyclin A, cyclin B, Rb, GAPDH, c-myc, and histone H4
      genes for sensitivity to okadaic acid in HeLa cells to determine if
      transformation altered their regulation. Serum starvation slowed growth and
      diminished mRNA levels for all genes tested except c-myc and GAPDH. When starved
      cells were subsequently exposed to 19 nM okadaic acid or refed 10% serum, mRNA
      levels of cyclin A, cyclin B, cdk1, and Rb dramatically increased while mRNA
      levels for c-myc and GAPDH were largely unaffected. Histone H4 mRNA levels and
      the rate of DNA synthesis were greatly enhanced by serum addition but not
      affected appreciably by okadaic acid. Okadaic acid was also effective in blocking
      proliferation of exponentially growing HeLa cells at G2/M and S phase. Despite
      the cell cycle phase-specific block, elevated mRNA levels for cdk1, cyclin A,
      cyclin B, Rb, and suppression of H4 mRNA levels were detected and persisted for
      at least 12 hr following okadaic acid removal. The results demonstrate that cell
      cycle progression is blocked and several cell cycle regulatory genes, encoding
      transcription factor E2F-associated proteins, experience elevation of mRNA levels
      through mechanisms sensitive to okadaic acid likely through a PP1/PP2A-sensitive
      mechanism. Data from transformed cells contrast with data from immortalized but
      nontransformed cells in which okadaic acid also blocks cell cycle progression
      during G2/M phase but suppresses expression of these genes. Such contrasts may be
      correlated with reduced growth factor dependence and transformation.

PMID- 7622589
TI  - Regulation of platelet-derived growth factor A and B chain gene expression in
      bone marrow stromal cells.
AB  - MBA-2, bone marrow-derived endothelial stromal cells, express platelet-derived
      growth factor (PDGF) A and B chain mRNAs and secrete PDGF activity that is
      induced by TGF-beta. Either chain of the PDGF molecule could modulate
      hematopoiesis and stromal cell growth. Intracellular pathways that regulate PDGF
      expression in the marrow microenvironment are unknown. In the present study, we
      examined the mechanisms that mediate PDGF A and B chain mRNA induction by TGF
      beta and the role of protein kinase C (PKC) and cyclic AMP in PDGF regulation.
      TGF-beta was tested in parallel with PMA, an activator of phorbol ester-dependent
      PKC isoforms. Both PMA (10(-7)M) and TGF-beta (2.5 ng/ml) increased PDGF A and B
      chain mRNA levels. The serine/threonine protein kinase inhibitor, H7, blocked
      PDGF A and B chain mRNA induction in response to TGF-beta. However, down
      regulation of PKC by prolonged incubation with PMA failed to abolish TGF-beta
      induction of PDGF A and B chain mRNAs. These findings indicate that induction of
      PDGF A and B chain mRNAs can be mediated via phorbol ester-dependent PKC pathway.
      In contrast, H7-sensitive protein kinase(s) other than phorbol ester-sensitive
      protein kinase C mediate the effect of TGF-beta. Agents that increase cAMP were
      also tested for their effect on PDGF gene expression. TGF-beta-mediated induction
      of PDGF A and B chain mRNAs was markedly inhibited by cAMP. cAMP also blocked
      stimulation of PDGF A chain mRNA by PMA. The positive and negative signaling
      mechanisms involved in modulating PDGF in the microenvironment may be important
      for determining hematopoietic and stromal cell responses in vivo.

PMID- 7622590
TI  - Differential localization of protein kinase C isozymes in U937 cells: evidence
      for distinct isozyme functions during monocyte differentiation.
AB  - U937 human promonocytic leukemia cells express PKC isozymes beta 1, beta 2,
      epsilon and zeta. Indirect immunocytofluorescence using affinity-purified PKC
      specific antibodies indicates that each of the endogenous PKC isozymes in U937
      cells display a unique compartmentalization within the intact cell. PKC-beta 1 is
      distributed between two identifiable pools: a cytoplasmic pool which
      redistributes to the plasma membrane upon activation with acute phorbol ester
      treatment, and a membrane-bound pool associated with intracellular vesicles
      containing beta 2-integrin adhesion molecules, cd11b and cd11c. The vesicle
      associated PKC-beta 1 translocates with the secretory granules to the plasma
      membrane upon agonist-stimulated activation. PKC-beta 2 is associated with the
      microtubule cytoskeleton in resting cells. PKC overlay assays indicate that PKC
      beta 2 binds to proteins associated with microtubules, and not directly to
      tubulin. PKC-epsilon is associated with filamentous structures in resting cells
      and redistributes to the perinuclear region upon activation with phorbol esters.
      In differentiated U937 cells, PKC-beta 1 remains associated with vesicles
      translocating from the trans-Golgi region to the plasma membrane and PKC-epsilon
      is primarily associated with perinuclear and plasma membranes. PKC-zeta, which
      does not respond to phorbol ester treatment, is primarily cytosolic in
      undifferentiated cells and accumulates in the nucleus of differentiated cells
      blocked in the G2 phase of the cell cycle. The data clearly demonstrate that
      individual PKCs localize to different subcellular compartments and promote the
      hypothesis that PKC subcellular localization is indicative of unique functions
      for individual PKC isozymes.

PMID- 7622591
TI  - Gap junction regulation in the uterus and ovaries of immature rats by estrogen
      and progesterone.
AB  - The effects of estrogen (E2) and progesterone (P) were examined on the expression
      levels of multiple gap junction (GJ) gene products (alpha 1 = Cx43, beta 1 =
      Cx32, beta 2 = Cx26) in the uterus and ovaries of immature rats by
      immunohistochemistry, electron microscopy and northern blot analysis. E2 induced
      the expression of alpha 1 connexin in the uterus (specifically in the myometrium
      and in endometrial stroma proximal to luminal epithelium) and ovaries. The E2
      induced alpha 1 expression was completely suppressed by P in the uterus, but only
      partly in ovaries. Steroid hormones also modulated the quantity, size, and
      distribution of beta 1 and beta 2 containing junctional plaques along lateral
      cell borders in polarized luminal and glandular uterine epithelia. Small GJs were
      detected at basolateral regions in proliferative luminal epithelium following
      administration of E2. In contrast, large GJs were localized at subapical-lateral
      cell borders of the secretory epithelium following P-treatment. The co
      administration of E2 + P had a synergistic effect on beta 1 and beta 2 expression
      in the luminal epithelium, but an inhibitory effect on beta 2 expression in
      glandular epithelium. Myometrial GJs were detected in freeze-fracture replicas as
      aggregates containing regularly arranged particles with particle free zones. In
      contrast, GJs in secretory epithelium contained particles which were arranged in
      a non-crystalline fashion. These GJs contained domains of mixed and segregated
      beta 1 and beta 2 antigens within a single plaque as revealed by laser scanning
      confocal microscopy analysis of immuno-double-labeled secretory epithelium. The
      demonstration of segregated antigens within a single GJ plaque indicates the
      possibility of multiple channel populations formed by homo-oligomeric connexons.
      These results suggest that different connexins can be differentially regulated by
      steroid hormones in different cell types, and that the same steroid hormone can
      have different effects on the same connexin in different cell types.

PMID- 7622592
TI  - Characterisation of shrimp haemocytes and plasma components by monoclonal
      antibodies.
AB  - Various haemolymph components of the shrimp Penaeus japonicus were identified and
      characterised by monoclonal antibodies. Three groups of monoclonal antibodies
      were raised. Their reactivity to haemocyte types and/or secreted molecules was
      determined by immunofluorescence and the molecular masses of the antigens were
      analysed by western-blotting. A 170 kDa protein, in reducing conditions, was
      recognized by four panhaemocytic monoclonal antibodies from group 1. This protein
      was present both in the plasma and in the haemocytes from which it appears to be
      secreted. The shrimp haemocytes were separated by isopycnic centrifugation on a
      Percoll gradient and the different subpopulations were antigenically analysed
      using the two monoclonal antibodies, 40E2-2A and 40E10-2B, from group 2. The
      granular cells were labelled by 40E2-2A which was specific for a protein of 142
      kDa also present in plasma. By comparison, the 40E10-2B monoclonal antibody was
      assumed to be the marker for small hyaline and semigranular cells since the
      granular ones were not labelled. Moreover, the antigen immunoprecipitated by this
      monoclonal antibody was shown to have different molecular masses of 250, 150, 66
      and 27 kDa under nonreducing conditions. It appeared to be secreted by the
      haemocytes. Some plasma proteins were recognized by the third group of monoclonal
      antibodies. The antibodies, designated 41D11-3A, 42C11-3B and 42E8-3C, all
      immunoprecipitated a protein with an apparent molecular mass of 180 kDa under
      reduced conditions. The 44E6-3D antibody was specific for a 75 kDa protein under
      reduced conditions and was shown to be immunoreactive against P. japonicus
      haemocyanin extract.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7622593
TI  - Mapping of adherens junction components using microscopic resonance energy
      transfer imaging.
AB  - Quantitative microscopic imaging of resonance energy transfer (RET) was applied
      for immunological high resolution proximity mapping of several cytoskeletal
      components of cell adhesions. To conduct this analysis, a microscopic system was
      developed, consisting of a highly stable field illuminator, computer-controlled
      filter wheels for rapid multiple-color imaging and a sensitive, high resolution
      CCD camera, enabling quantitative data recording and processing. Using this
      system, we have investigated the spatial inter-relationships and organization of
      four adhesion-associated proteins, namely vinculin, talin, alpha-actinin and
      actin. Cultured chick lens cells were double labeled for each of the junctional
      molecules, using fluorescein- and rhodamine-conjugated antibodies or phalloidin.
      RET images were acquired with fluorescein excitation and rhodamine emission
      filter setting, corrected for fluorescein and rhodamine fluorescence, and
      normalized to the fluorescein image. The results pointed to high local densities
      of vinculin, talin and F-actin in focal adhesions, manifested by mean RET values
      of 15%, 12% and 10%, respectively. On the other hand, relatively low values (less
      than 1%) were observed following double immunofluorescence labeling of the same
      cells for alpha-actinin. Double indirect labeling for pairs of these four
      proteins (using fluorophore-conjugated antibodies or phalloidin) resulted in RET
      values of 5% or lower, except for the pair alpha-actinin and actin, which yielded
      significantly higher values (13-15%). These results suggest that despite their
      overlapping staining patterns, at the level of resolution of the light
      microscope, the plaque proteins vinculin and talin are not homogeneously
      interspersed at the molecular level but form segregated clusters. alpha-Actinin,
      on the other hand, does not appear to form such clusters but, rather, closely
      interacts with actin. We discuss here the conceptual and applicative aspects of
      RET measurements and the implications of the results on the subcellular molecular
      organization of adherens-type junctions.

PMID- 7622595
TI  - Identification of intrinsic dimer and overexpressed monomeric forms of gamma
      tubulin in Sf9 cells infected with baculovirus containing the Chlamydomonas gamma
      tubulin sequence.
AB  - A new member of the tubulin superfamily, gamma-tubulin, is localized at
      microtubule-organizing centers (MTOCs) in a variety of organisms. Chlamydomonas
      cDNA coding for the full-length sequence of gamma-tubulin was expressed in insect
      ovarian Sf9 cells using the baculovirus expression system. Approximately half of
      the induced 52 kDa gamma-tubulin was recovered in the supernatant after
      centrifugation of Sf9 cell lysates at 18,000 g for 15 minutes. When the cell
      supernatant was analyzed by FPLC on a Superdex 200 sizing column, Chlamydomonas
      gamma-tubulin separated into two major peaks. The lagging peak contained a
      monomeric form of gamma-tubulin with a sedimentation coefficient of 2.5 S, which
      interacted with the Superdex column in a salt-dependent manner. The leading peak,
      with an apparent molecular mass of 900 kDa, corresponded to a molecular
      chaperonin complex, and TCP1 chaperonin released folded gamma-tubulin polypeptide
      from the complex in the presence of MgATP. The released gamma-tubulin monomers
      were capable of binding to microtubules in vitro and biochemical quantities of
      active monomers were further purified using a combination of size-exclusion and
      ion-exchange column chromatography. The endogenous Sf9 cell gamma-tubulin
      migrated faster than Chlamydomonas gamma-tubulin with an apparent molecular mass
      of 49 kDa on gels. Analyses on gel filtration and sucrose density gradient
      centrifugation showed that, while overexpressed Chlamydomonas gamma-tubulin was
      present in a monomeric form, endogenous gamma-tubulin from Sf9 and HeLa cells
      exists as a dimer. These results may suggest the possibility that gamma-tubulin
      could form a heterodimer with hitherto unknown molecule(s).

PMID- 7622594
TI  - Scanning force microscopy of microtubules and polymorphic tubulin assemblies in
      air and in liquid.
AB  - We have investigated microtubules (MTs) and polymorphic assemblies, formed in
      vitro from isolated microtubule protein, by scanning force microscopy (SFM) in
      air and in liquid. Immobilization of MTs was achieved by placing a drop of the
      assembly solution on a polylysine-coated coverslip. After washing with taxol and
      air drying, the characteristic microtubular fibrous morphology appeared in the
      SFM. The MTs formed a network similar to that obtained by transmission electron
      microscopy (TEM). A height of approximately 9.5 nm for dried MTs was computed
      from the surface topography. Glutaraldehyde fixation of the MTs yielded higher
      structures (approximately 14 nm), which swelled to approximately 20 nm after
      rehydration, a value close to the MT diameter of approximately 25 nm determined
      from TEM images of ultrathin sections. The protofilament pattern of the MTs and
      surface attached MT-associated proteins were not apparent from SFM, although the
      height along the long axis of the MTs appeared slightly modulated. In addition to
      MTs, various polymorphic tubulin assemblies including ribbons, hoops and double
      walled MTs were visualized by SFM.

PMID- 7622596
TI  - Molecular genetic analysis of myoC, a Dictyostelium myosin I.
AB  - The protozoan myosin Is are widely expressed actin-based motors, yet their in
      vivo roles remain poorly understood. Molecular genetic studies have been carried
      out to determine their in vivo function in the simple eukaryote Dictyostelium, an
      organism that contains a family of four myosin Is. Here we report the
      characterization of myoC, a gene that encodes a fifth member of this family.
      Analysis of the deduced amino acid sequence reveals that the myoC gene encodes a
      myosin that is homologous to the well-described Acanthamoeba myosin Is as well as
      to Dictyostelium myoB and -D. The expression pattern of the myoC mRNA is similar
      to that of myoB and myoD, with a peak of expression at times of maximal cell
      migration, around 6 hours development. Deletion of the myoB gene has been
      previously shown to result in mutant cells that are defective in pseudopod
      extension and phagocytosis. However, no obvious differences in cell growth,
      development, phagocytosis or motility were detected in cells in which the myoC
      gene had been disrupted by homologous recombination. F-actin localization and
      ultrastructural organization also appeared unperturbed in myoC- cells. This
      apparent 'lack' of phenotype in a myosin I single knockout cannot be simply
      explained by redundancy of function. Our results rather suggest that the present
      means of assessing myosin I function in vivo are insufficient to identify the
      unique roles of these actin-based motors.

PMID- 7622597
TI  - Mutants lacking myosin II cannot resist forces generated during multicellular
      morphogenesis.
AB  - We have used fluorescent labeling, confocal microscopy and computer-assisted
      motion analysis to observe and quantify individual wild-type and myosin II mutant
      cell behavior during early multicellular development in Dictyostelium discoideum.
      When cultured with an excess of unlabeled wild-type cells, labeled control cells
      are randomly distributed within aggregation streams, while myosin II mutant cells
      are found primarily at the lateral edges of streams. Wild-type cells move at
      average rates of 8.5 +/- 4.9 microns/min within aggregation streams and can
      exhibit regular periodic movement at 3.5 minute intervals; half as long as the 7
      minute period reported previously for isolated cells. Myosin II mutants under the
      same conditions move at 5.0 +/- 4.8 microns/min, twice as fast as reported
      previously for isolated myosin II mutant cells, and fail to display regular
      periodic movement. When removed from aggregation streams myosin II mutant cells
      move at only 2.5 +/- 2.0 microns/min, while wild-type cells under these
      conditions move at 5.9 +/- 4.5 microns/min. Analysis of cell morphology further
      reveals that myosin II mutant cells are grossly and dynamically deformed within
      wild-type aggregation streams but not when removed from streams and examined in
      isolation. These data reveal that the loss of myosin II has dramatic consequences
      for cells undergoing multicellular development. The segregation of mutant cells
      to aggregation stream edges demonstrates that myosin II mutants are unable to
      penetrate a multicellular mass of wild-type cells, while the observed distortion
      of myosin II mutant cells suggests that the cortex of such cells is too flacid to
      resist forces generated during movement. The increased rate of mutant cell
      movement and distortion of mutant cell morphology seen within wild-type
      aggregation streams further argues both that movement of wild-type cells within a
      multicellular mass can generate traction forces on neighboring cells and that
      mutant cell morphology and behavior can be altered by these forces. In addition,
      the distortion of myosin II mutant cells within wild-type aggregation streams
      indicates that myosin is not required for the formation of cell-cell contacts.
      Finally, the consequences of the loss of myosin II for cells during multicellular
      development are much more severe than has been previously revealed for isolated
      cells. The techniques used here to analyze the behavior of individual cells
      within multicellular aggregates provide a more sensitive assay of mutant cell
      phenotype than has been previously available and will be generally applicable to
      the study of motility and cytoskeletal mutants in Dictyostelium.

PMID- 7622598
TI  - High molecular weight polypeptides related to dynein heavy chains in Nicotiana
      tabacum pollen tubes.
AB  - Nicotiana tabacum pollen tubes contain two high molecular weight polypeptides
      (about 400 kDa), which are specifically expressed during pollen germination and
      pollen tube growth in BK medium. The high molecular weight doublet resembles the
      dynein heavy chains in some biochemical properties. Sedimentation profiles of
      pollen tube extracts show that the high molecular weight bands have sedimentation
      coefficients of 22 S and 12 S, respectively. ATPase assay of sedimentation
      fractions shows an activity ten times higher when stimulated by the presence of
      bovine brain microtubules in fractions containing the 22 S high molecular weight
      polypeptide. Both these high molecular weight polypeptides can bind microtubules
      in an ATP-dependent fashion. A mouse antiserum to a synthetic peptide reproducing
      the sequence of the most conserved ATP-binding site among dynein heavy chains
      recognized the two high molecular weight polypeptides. Therefore these
      polypeptides have sequences immunologically related to the ATP binding sites of
      dynein heavy chains.

PMID- 7622599
TI  - Fast freeze-fixation/freeze-substitution reveals the secretory membranes of the
      gastric parietal cell as a network of helically coiled tubule. A new model for
      parietal cell transformation.
AB  - The parietal cell of the gastric mucosa undergoes rapid morphological
      transformation when it is stimulated to produce hydrochloric acid. In chemically
      fixed cells, this process is seen as a reduction in number of cytoplasmic
      'tubulovesicles' as the apical surface of the cell progressively invaginates to
      increase the secretory surface area. It is widely believed that the
      tubulovesicles represent stored secretory membrane in the cytoplasm of the
      unstimulated cell, which is incorporated into the apical membrane upon
      stimulation, because they share H+,K+-ATPase activity with the apical membrane.
      However, fusion of tubulovesicles with the apical membrane concomitant with
      parietal cell activation has never been convincingly demonstrated. We have used
      fast freeze-fixation and freeze-substitution to study stages of morphological
      transformation in these cells. Tubulovesicles were not seen in the cytoplasm of
      any of our cryoprepared cells. Instead, the cytoplasm of the unstimulated cell
      contained numerous and densely packed helical coils of tubule, each having an
      axial core of cytoplasm. The helical coils were linked together by connecting
      tubules, lengths of relatively straight tubule. Lengths of straight connecting
      tubule also extended from coils lying adjacent to the apical and canalicular
      surfaces and ended at the apical and canaliculus membranes. Immunogold labelling
      with alpha- and beta-subunit-specific antibodies showed that the gastric H+,K+
      ATPase was localized to the membranes of this tubular system, which therefore
      represented the configuration of the secretory membrane in the cytoplasm of the
      unstimulated parietal cell. Stimulation of the cells with histamine and
      isobutylmethylxanthine lead to modification of the tubular membrane system,
      correlated with progressive invagination of the apical membrane. The volume of
      the tubule lumen increased and, as this occurred, the tight spiral twist of the
      helical coils was lost, indicating that tubule distension was accounted for by
      partial unwinding. This exposed the cores of cytoplasm in the axes of the coils
      as rod-shaped elements of a three-dimensional reticulum, resembling a series of
      microvilli in random thin sections. Conversely, treatment with the H2 antagonist
      cimetidine caused severe contraction of the tubular membrane system and
      intracellular canaliculi. Our results indicate that tubulovesicles are an
      artifact of chemical fixation; consequently, they cannot have a role in parietal
      cell transformation. From our findings we propose an alternative model for
      morphological transformation in the parietal cell. This model predicts
      cytoskeleton-mediated control over expansion and contraction of the tubular
      membrane network revealed by cryopreparation. The model is compatible with the
      localization of cytoskeletal components in these cells.

PMID- 7622600
TI  - p80-coilin: a component of coiled bodies and interchromatin granule-associated
      zones.
AB  - We investigated at the electron microscope level the fate of the three
      intranuclear structures known to accumulate snRNPs, and which correspond to the
      punctuate immunofluorescent staining pattern (the coiled bodies, the clusters of
      interchromatin granules and the interchromatin granule-associated zones) after
      exposure to either a low salt medium which induces a loosening and partial
      spreading of nucleoprotein fibers or a high ionic strength salt medium and
      subsequent DNase I digestion, in order to obtain DNA-depleted nuclear matrices.
      The loosened clusters of interchromatin granules and the coiled bodies could no
      longer be distinguished from surrounding nucleoprotein fibers solely by their
      structure, but constituents of the clusters of interchromatin granules could be
      detected by in situ hybridization with both U1 and U2 DNA probes, and
      constituents of the coiled bodies were detectable mainly with the U2 DNA probe.
      The interchromatin granule-associated zones, the electron-opacity and compactness
      of which were preserved despite the loosening treatment, remained labeled with
      the U1 DNA probe only. In DNA-depleted nuclear matrices, the snRNA content of the
      coiled bodies, the clusters of interchromatin granules and their associated
      zones, which were all easily recognizable within the residual nuclear
      ribonucleoprotein network, was unmodified. The data indicate, therefore, that the
      loosening procedure as well as the high salt extraction procedure preserve the
      snRNA content of all three spliceosome component-accumulation sites and reveal
      that interchromatin granule-associated zones are elements of the nuclear matrix.
      The p80-coilin content coiled bodies was also preserved whatever the salt
      treatment used. An intriguing new finding is the detection of abundant p80-coilin
      within the interchromatin granule-associated zones, both before and after either
      low or high salt treatment of cells. Therefore, p80-coilin is an integral
      constituent of the interchromatin granule-associated zones.

PMID- 7622601
TI  - The functional thrombin receptor is associated with the plasmalemma and a large
      endosomal network in cultured human umbilical vein endothelial cells.
AB  - The functional thrombin receptor, normally expressed by endothelial cells and
      platelets, is a member of the G protein-coupled, seven membrane-spanning-domain
      receptor family and is thought to be responsible for most, if not all, the cell
      stimulatory effects of thrombin. Upon binding, thrombin cleaves the receptor's N
      terminal ectodomain, unmasking a new N terminus, which by itself activates the
      receptor. Using antibodies to different domains of the human thrombin receptor,
      we have localized the receptor in cultured human umbilical vein endothelial cells
      by indirect immunofluorescence and immunoelectron microscopy. We found the
      receptor expressed on the plasmalemma of cultured endothelial cells in individual
      units rather than in clusters, at lower concentration than, and at different
      sites from, thrombomodulin. We also found the receptor associated with a
      distinct, intracellular, transferrin receptor-containing, tubulovesicular
      network. The thrombin receptor-positive structure spread from the perinuclear
      region to the periphery of the cells, exhibiting a number of varicosities
      interconnected by branching tubular elements, strikingly similar to an image
      recently described for a continuous endosomal reticulum. Our results provide
      morphological evidence for the presence of the functional thrombin receptor at
      relative low density on the surface of cultured endothelial cells (compared to
      thrombomodulin) and in relatively large quantities inside the cells, associated
      with an endosomal compartment.

PMID- 7622603
TI  - Change in intracellular K+ concentration caused by external osmolality change
      regulates sperm motility of marine and freshwater teleosts.
AB  - We previously demonstrated that osmolality isotonic to the seminal plasma
      suppresses sperm motility in marine and freshwater teleosts, and exposure of
      sperm to hypertonicity of sea water or hypotonicity of fresh water, respectively,
      induces the initiation of sperm motility at spawning. The motile sperm became
      immotile by return of osmolality to the isotonic osmolality both in a marine
      teleost, the puffer fish, and a freshwater teleost, the zebrafish. The initiation
      and termination of sperm motility could be repeated several times by changing
      surrounding osmolality in both species. In demembranated sperm, motility was
      suppressed by a K+ concentration equivalent to the seminal salt concentration in
      both puffer and zebrafish. Demembranated puffer sperm were reactivated when K+
      concentration of the reactivating solution increased. Conversely, initiation of
      motility in the demembranated zebrafish sperm was induced by decreasing K+
      concentration. The initiation and termination of the demembranated sperm were
      alternately repeated by changing K+ concentration of the reactivation solution in
      both species. Furthermore, intracellular K+ concentration rose when sperm
      motility of the puffer was initiated in hypertonic solutions. These results
      suggest that change in external osmolality is converted into change in
      intracellular K+ concentration, and that the change affects the flagellar axoneme
      as a signal to initiate or terminate sperm motility. The initiation and
      termination of motility in the demembranated puffer sperm were caused at a high
      pH and a low pH of the reactivating solution, respectively, suggesting the
      contribution of intracellular pH in the regulation of flagellar motility.

PMID- 7622602
TI  - Stimulation of tyrosine phosphorylation of distinct proteins in response to
      antibody-mediated ligation and clustering of alpha 3 and alpha 6 integrins.
AB  - The interaction of cells with components of the extracellular matrix through
      their integrin receptors results in the stimulation of tyrosine phosphorylation
      of several proteins, suggesting that these receptors play a key role in signal
      transduction. Here we report that antibody-mediated ligation and clustering of
      alpha 3 beta 1 and alpha 6 beta 1/alpha 6 beta 4 integrins resulted in the
      stimulation of tyrosine phosphorylation of proteins that are specific for each
      heterodimer. Thus, ligation and clustering of the alpha 3 beta 1 integrin on
      human prostate carcinoma cells (PC-3) and human umbilical vein endothelial cells
      (HUVEC) with anti-alpha 3 antibodies resulted in the stimulation of tyrosine
      phosphorylation of a 55 kDa protein. In contrast, ligation and clustering of the
      alpha 6 beta 1 integrin on these cells with anti-alpha 6 antibody resulted in the
      dramatic stimulation of tyrosine phosphorylation of a 90 kDa protein in addition
      to a 52 kDa protein, and ligation and clustering of alpha 5 beta 1 on HUVEC did
      not result in the apparent stimulation of tyrosine phosphorylation of any
      proteins. Clustering with anti-beta 1 antibodies triggered the tyrosine
      phosphorylation of all of these proteins, whereas ligation and clustering of PC-3
      cells with an anti-beta 4 antibody resulted in the tyrosine phosphorylation of a
      distinct 62 kDa protein. Since the PC-3 cells express both alpha 6 beta 1 and
      alpha 6 beta 4, these data suggest that these two receptors can transduce
      distinct signals. All of the phosphorylations could be inhibited by treating the
      cells with Genistein, a tyrosine kinase inhibitor. Antibody-mediated ligation and
      clustering of integrins on the two types of cells did not result in the
      stimulation of tyrosine phosphorylation of pp125 focal adhesion kinase, although
      this was observed upon cell attachment and spreading on fibronectin, laminin and
      anti-alpha 3 monoclonal antibody. Collectively, these data demonstrate that cross
      linking of different integrin heterodimers can stimulate tyrosine kinase
      activities, leading to the phosphorylation of distinct proteins, which are also
      different from those observed when cells are allowed to spread on a matrix.

PMID- 7622604
TI  - Suppression of a conditional mutation in alpha-tubulin by overexpression of two
      checkpoint genes.
AB  - To identify proteins that regulate microtubule assembly in Saccharomyces
      cerevisiae, we screened for multicopy suppressors of a conditional mutation in
      alpha-tubulin. Cells expressing the recessive allele tub1-729 as their sole alpha
      tubulin gene grow normally at permissive temperature. However, at 15 degrees C
      the cells lose viability and arrest primarily with large buds and quantitatively
      diminished microtubule structures. Transformation of mutant cells with genomic
      libraries repeatedly identified three different suppressors: the two wild-type
      alpha-tubulin genes, TUB1 and TUB3; and BUB3. BUB3 is a checkpoint gene that
      permits entry into mitosis depending upon the assembly state of microtubules.
      Excess BUB3 rescues both the loss of viability and microtubule defects but not
      the benomyl supersensitivity associated with tub1-729. The suppression is
      specific for the mutation ALA422VAL in TUB1, and does not affect several other
      mutations in TUB1 that produce the 'no microtubule' phenotype. Overexpression of
      BUB1, which interacts genetically with BUB3 and which is involved in the same
      checkpoint pathway, also rescues the cold sensitivity of tub1-729, but another
      checkpoint gene, MAD2, does not. Overexpression of BUB3 in wild-type cells has no
      detectable growth or microtubule defect, but disruption of the BUB3 gene produces
      slow growth and benomyl supersensitivity. Our results suggest that BUB1 and BUB3
      overexpression modulate an event required for mitotic spindle function which is
      rate limiting for tub1-729 cells at the restrictive temperature.

PMID- 7622605
TI  - The levels of ubiquitinated histone H2A are highly upregulated in transformed
      human cells: partial colocalization of uH2A clusters and PCNA/cyclin foci in a
      fraction of cells in S-phase.
AB  - The levels and distribution of ubiquitinated histone H2A (uH2A) have been studied
      in normal and transformed human cells using a monoclonal antibody (mAb E6C5) that
      reacts specifically with this ubiquitin conjugate as determined by two
      dimensional gel western blotting and microsequencing. Immunoblotting experiments
      demonstrated that the levels of the protein are highly upregulated in SV40
      transformed human fibroblasts (WI-38 SV40) and keratinocytes (K14) relative to
      their normal counterparts, a finding that was further confirmed by indirect
      immunofluorescence studies of formaldehyde/Triton X-100-treated cells, which
      showed that about 97% of the transformed cells and 26% of the normal populations
      reacted with the antibody to yield a fine granular nuclear staining associated
      with the chromatin. Transformed cells contained in addition clusters of uH2A that
      were quite abundant and that showed variable size, shape and distribution even
      within a single cell line. The clusters, which were rare in normal cells, did not
      colocalize with other known nuclear antigens and may correspond to novel nuclear
      domains where ubiquitination/deubiquitination takes place. Electron microscopic
      immunocytochemistry of K14 cells confirmed the existence of the clusters. Double
      immunofluorescence studies of K14 keratinocytes with proliferating cell nuclear
      antigen (PCNA)/cyclin antibodies, which react with the nuclei of cells engaged in
      DNA replication, showed partial colocalization of PCNA/cyclin foci and large uH2A
      clusters in about 14% of the S-phase cells, and these corresponded mainly to late
      S-phase cells. Inhibition of DNA replication with hydroxyurea resulted in an
      overall increase in the intensity of the uH2A staining as well as in a more clear
      colocalization of uH2A clusters and PCNA/cyclin foci. Taken together, the results
      support the contention that uH2A plays a role at some stage of DNA replication.

PMID- 7622607
TI  - Dynamics of fibroblast spreading.
AB  - A new technique of microinterferometry permits cellular growth and motile
      dynamics to be studied simultaneously in living cells. In isolated chick heart
      fibroblasts, we have found that the non-aqueous mass of each cell tends to
      increase steadily, with minor fluctuations, throughout the cell cycle. The spread
      area of each cell also tends to increase during interphase but fluctuates between
      wide limits. These limits are dependent on the cell's mass and the upper limit is
      particularly sharp and directly proportional to mass. From a dynamical point of
      view, the spread area of a cell is determined by the balance between the rates of
      two antagonistic processes: protrusion of cellular material into new territory
      and retraction of material from previously occupied territory. The spatial
      asymmetry of these processes determines the translocation of the cell. We have
      found with the chick fibroblasts that the rates of the two processes are
      generally closely matched to each other and appear to be dependent on the cell's
      area of spreading. Both continue incessantly in well spread cells, even when
      there is no net translocation of the cell, and the lower limit of each activity
      is directly proportional to spread area. The two processes show different
      behaviour, however, during changes in the spread area of the cell. Both increases
      and decreases in area appear to be brought about by changes in the rate of
      retraction, the rate of protrusion remaining relatively constant. A simple
      stochastic model based on a limited supply of adhesion molecules can simulate all
      our observations including the mass-limited spreading, the strong correlation
      between protrusion and retraction and the retraction-dominated changes in area.
      We conclude that the spread area of the cell is actively regulated, possibly by a
      simple automatic mechanism that adjusts the area of spreading in relation to the
      mass of the cell and controls the rate of protrusion to compensate rapidly for
      spontaneous fluctuations in retraction.

PMID- 7622606
TI  - Regulation of Cdc2/cyclin B activation by Ran, a Ras-related GTPase.
AB  - During the cell cycle, a checkpoint prevents the initiation of mitosis until S
      phase is completed. The molecular mechanism may involve the RCC1 protein, which
      catalyses guanine nucleotide exchange on the Ras-related nuclear protein, Ran (or
      TC4). Genetic studies have suggested that RCC1 may be involved in sensing the
      replication state of DNA and controlling the activation of Cdc2/cyclin B protein
      kinase through Ran. In this report, we present direct biochemical evidence for
      the post-translational control of Cdc2/cyclin B activation by Ran. In a cell-free
      system of concentrated Xenopus egg extracts supplemented with nuclei, a mutant
      form of Ran (T24N) analogous to dominant inactive mutants of other Ras-related
      GTPases inhibits Cdc2/cyclin B activation in the presence of replicating nuclear
      DNA. This role for Ran is mediated through control of the tyrosine
      phosphorylation state of Cdc2 and appears to be distinct from other effects on
      nuclear import, nuclear formation and DNA replication. When extracts were
      supplemented with RCC1 protein prior to addition of Ran T24N, inhibition of
      Cdc2/cyclin B by Ran T24N was relieved. This suggests that Ran T24N may act in a
      dominant manner by sequestering RCC1 in an inactive form. In contrast to Ran
      T24N, a mutant of Ran (Q69L) defective in GTPase activity and hence locked in the
      GTP-bound state has no inhibitory effect on Cdc2/cyclin B activation. In the
      light of these results, we propose that generation of the GTP-bound form of Ran
      is required for Cdc2/cyclin B activation and entry into mitosis when this process
      is coupled to the progression of S-phase.

PMID- 7622608
TI  - Collagen matrices attenuate the collagen-synthetic response of cultured
      fibroblasts to TGF-beta.
AB  - Transforming growth factor-beta, a potent modulator of cell function, induces
      fibroblasts cultured on plastic to increase collagen synthesis. In 5- and 7-day
      porcine skin wounds, which have minimal to moderate collagen matrix,
      respectively, transforming growth factor-beta and type I procollagen were
      coordinately expressed throughout the granulation tissue. However, in 10-day
      collagen-rich granulation tissue type I procollagen expression diminished despite
      persistence of transforming growth factor-beta. To investigate whether collagen
      matrix attenuates the collagen-synthetic response of fibroblasts to transforming
      growth factor-beta, we cultured human dermal fibroblasts in conditions that
      simulate collagen-rich granulation tissue. Therefore, human dermal fibroblasts
      were suspended in attached collagen gels and collagen and noncollagen production
      was assayed in the absence and presence of transforming growth factor-beta.
      Although transforming growth factor-beta stimulated collagen synthesis by
      fibroblasts cultured in the collagen gels, these fibroblasts consistently
      produced less collagen than similarly treated fibroblasts cultured on plastic.
      This phenomenon was not secondary to nonspecific binding of transforming growth
      factor-beta to the collagen matrix. Fibroblasts cultured in a fibrin gel
      responded to transforming growth factor-beta similarly to fibroblasts cultured on
      plastic. Using immunofluorescence probes to type I procollagen, we observed that
      transforming growth factor-beta increased type I procollagen expression in most
      fibroblasts cultured on plastic, but only in occasional fibroblasts cultured in
      collagen gels. From these data we conclude that collagen matrices attenuate the
      collagen synthetic response of fibroblast to transforming growth factor-beta in
      vitro and possibly in vivo.

PMID- 7622609
TI  - Rapid bulk replacement of acceptor membrane by donor membrane during phagosome to
      phagoacidosome transformation in Paramecium.
AB  - The extent to which a donor membrane will be retrieved, or if it is retrieved at
      all after it fuses with an acceptor membrane, is usually difficult to determine.
      We have studied the dynamics of membrane retrieval in the phagosome system of
      Paramecium multimicronucleatum using six monoclonal antibody markers. Our
      previous freeze-fracture and transmission electron microscopic studies have
      indicated that extensive changes take place in the membrane of the young
      phagosome as it progresses through its cycle. Using immunofluorescence and
      immunoelectron microscopy to determine the times of entry and exit of these
      individual antigens into the digestive vacuole system, we showed that two
      hydrophilic antigens, one located on the cytosolic and one on the lumenal side of
      the discoidal membrane (phagosome membrane precursor), were completely retrieved
      from the phagosome by tubulation within the first three minutes. At the same time
      that this membrane was retrieved, membrane from a second population of vesicles,
      the acidosomes, fused with the phagosome to produce the phagoacidosome. On the
      basis of immunogold localization on cryosections of a total of six antigens, the
      two specific for phagosome/discoidal vesicle membrane as well as four specific
      for the acidosome/phagoacidosome membrane, this replacement is total. We also
      showed that in the presence of the actin-active drug cytochalasin B, this
      replacement was essentially prevented. However, when vacuole acidification was
      neutralized by ammonium chloride, this replacement process continued unaffected
      after a lag. Consequently, acidification, per se, is not required to trigger the
      replacement of the phagosome membrane. We conclude, on the basis of these studies
      as well as our previous freeze-fracture studies that during phagoacidosome
      formation most of the acceptor membrane is retrieved and is replaced by the donor
      membrane. This shows that at least one cell type possesses the mechanisms needed
      to substantially replace the membrane of a phagosomal compartment when radical
      and rapid changes are needed to modulate the digestive and absorptive processes.

PMID- 7622610
TI  - Characterization of mucins and proteoglycans synthesized by a mucin-secreting HT
      29 cell subpopulation.
AB  - HT-29 cells selected by adaptation to 10(-5) M methotrexate (HT-29 MTX) are a
      homogeneous cell population producing high amounts of mucin. Intracellular mucins
      and proteoglycans were isolated from these cells by ultracentrifugation of cell
      lysates on a cesium bromide gradient and further separated by anion-exchange high
      performance liquid chromatography. The major mucin fraction isolated was
      characterized by a high hydroxy amino acid content (40%), a Thr/Ser ratio of
      1.52, a high sialic acid content, and a low sulfate content. When the same
      procedure was applied to undifferentiated HT-29 cells, a minor mucin fraction was
      isolated which appeared less sialylated and more sulfated. The major proteoglycan
      species identified in HT-29 MTX cells showed less acidic behavior than the
      proteoglycan isolated from HT-29 cells. The effect of brefeldin A and the sugar
      analog GalNAc-alpha-O-benzyl on the synthesis and biochemical properties of
      mucins synthesized by HT-29 MTX cells was examined. Brefeldin A induced the
      synthesis of more-sulfated mucins. GalNAc-alpha-O-benzyl treatment resulted in
      mucins with an increased content of T antigen and a 13-fold lower sialic acid
      content. We show that GalNAc-alpha-O-benzyl was metabolized by the cells to Gal
      beta 1-3GalNAc-alpha-O-benzyl, which, in turn, was a potent competitive inhibitor
      of the O-glycan alpha-2,3-sialyltransferase. These results illustrate the
      suitability of HT-29 MTX cells as a model to analyse mucin synthesis and
      sialylation.

PMID- 7622611
TI  - In vitro p53 and/or Rb antisense oligonucleotide treatment in association with
      growth factors induces the proliferation of peripheral hematopoietic progenitors.
AB  - In this work we intended to determine whether p53 and/or retinoblastoma (Rb)
      tumor suppressor genes are involved at specific stages in the process of in vitro
      human peripheral stem cell hematopoiesis. Mononuclear peripheral blood cells were
      depleted of adherent cells and T lymphocytes (A-T-PMCs). Cells were then cultured
      in semisolid medium, under conditions that favor the growth of specific
      progenitor cell types. A-T-PMCs were exposed to p53 and/or Rb sense, scrambled
      DNA and antisense oligodeoxynucleotides. p53 and/or Rb antisenses (but not their
      senses or scrambled DNA) treatment of A-T-PMCs resulted in a significantly
      increase in the number of granulocyte/macrophage colony-forming units (CFU-GM) in
      the presence of interleukin-3 (IL-3) and/or granulocyte/macrophage colony
      stimulating factor (GM-CSF). After antisense treatment, blast forming
      units/erythroblasts (BFU-E) derived from A-T-PMCs cultured in the presence of IL
      3 + erythropoietin (Epo) were also increased whereas colony forming
      units/erythroblasts (CFU-E) were not markedly affected in the presence of Epo
      only. Megakaryocytic colony (CFU-Meg) formation from A-T-PMCs in the presence of
      interleukin-6 (IL-6) + IL-3 + Epo was also increased after antisense
      oligodeoxynucleotide treatment. These results are consistent with the hypothesis
      that p53 and Rb tumor suppressor gene products are involved in the control of
      distinct signal pathways in different peripheral progenitor cells.

PMID- 7622612
TI  - Selective action of uncoating ATPase towards clathrin-coated vesicles from brain.
AB  - Clathrin-coated vesicles from brain are primarily involved in synaptic vesicle
      recycling and are substrates for the constitutively expressed heat shock cognate
      hsc70 protein (uncoating ATPase). To investigate the regulation of clathrin coat
      turnover in other tissues the activity of hsc70 towards coated vesicles from
      other sources was examined. Concentrations of hsc70 which caused near-complete
      removal of clathrin from brain coated vesicles effected only partial uncoating of
      vesicles prepared from other tissues. The selective action of hsc70 could not be
      accounted for by tissue or species specificities of hsc70, but rather reflected
      differences in coat structure. Selective action was associated with two
      differences in the hsc70-dependent ATPase cycle. Firstly, uncoating of brain, but
      not placental vesicles, could occur under circumstances where ATP hydrolysis was
      prevented. Secondly, only brain coated vesicles could support multiple rounds of
      hsc70-dependent ATP hydrolysis. Implications of these findings for the mechanism
      of hsc70-dependent vesicle uncoating in non-neuronal cells and the organisation
      of the endocytic pathway in the axon are discussed.

PMID- 7622613
TI  - Increased axon regeneration in astrocytes grown in the presence of proteoglycan
      synthesis inhibitors.
AB  - We have recently reported that the critical difference between astrocytic cell
      lines that are good or poor promoters of axon growth lies in the extracellular
      matrix. We demonstrated that much of this difference between matrix produced by
      permissive and non-permissive cell lines could be ascribed to one or more
      dermatan/keratan sulphate proteoglycans and that these proteoglycans are able to
      block the neurite-promoting effect of laminin. These proteoglycans are also
      produced by cultures of primary astrocytes. In the present study, we have
      demonstrated that treatment of both astrocytic cell lines and primary astrocytes
      with inhibitors of proteoglycan synthesis, beta-D-xylosides and sodium chlorate,
      can strongly influence the axon growth promoting properties of both matrix and
      whole cells. Dorsal root ganglia grown on matrix or in conditioned medium from
      cultures treated with beta-D-xylosides or sodium chlorate had twice as many axons
      and the axons grew to twice the length as in control cultures. Following
      treatment of Neu7 cells with proteoglycan synthesis inhibitors there was also a
      significant reduction in the ability of Neu7 conditioned medium to block the
      neurite-promoting effect of laminin. Dorsal root ganglia grown on Neu7 cells
      treated with sodium chlorate extended 2 to 3 times the number of axons for
      approximately 300 mm longer distance than on control cultures. Treatment of Neu7
      cells with beta-D-xylosides, however, did not make the cells less inhibitory to
      axon growth. We have also examined the effects of proteoglycan synthesis
      inhibitors on three-dimensional primary astrocyte cultures, which closely mimic
      the in vivo effects of astrocytes on axon growth.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7622614
TI  - Cysteine-to-arginine point mutation in a 'hybrid' eight-cysteine domain of FBN1:
      consequences for fibrillin aggregation and microfibril assembly.
AB  - Mutations in the FBN1 gene encoding the microfibrillar glycoprotein fibrillin
      cause Marfan syndrome, a relatively common autosomal dominant connective tissue
      disease. Causative FBN1 mutations appear to be dispersed throughout the coding
      frame, and to date no predictable genotype: phenotype correlations have emerged.
      We have identified a point mutation within an eight-cysteine 'hybrid' motif of
      the fibrillin polypeptide which results in the substitution of an arginine for a
      cysteine, in a patient severely affected in the cardiovascular, skeletal and
      ocular systems. We have utilised cell cultures from various tissues of this
      patient to investigate the effects of this mutation on fibrillin expression and
      deposition, and the consequences in terms of microfibril assembly and
      organisation. We have established that there is no difference in the expression
      of normal and mutant alleles, and fibrillin synthesis, secretion and deposition
      are also normal. However, the rate of fibrillin aggregation is reduced and
      microfibrillar assemblies are both remarkably scarce and morphologically
      abnormal. These data clearly demonstrate that the mutated allele interferes with
      normal assembly, and strongly implicate this particular region of the fibrillin-1
      molecule in stabilising microfibrillar assemblies.

PMID- 7622616
TI  - Putative myosin heavy and light chains in Tetrahymena: co-localization to the
      basal body-cage complex and association of the heavy chain with skeletal muscle
      actin filaments in vitro.
AB  - The basal body cage is a fibrillar chamber which surrounds each basal body in the
      ciliate cytoskeleton. The function of this chamber is unknown. In Tetrahymena,
      the cage contains actin filaments which connect the cage to triplet microtubules.
      In this study, we have examined the cage for the presence of myosin. Skeletal
      muscle myosin-II heavy and light chains were used to affinity-purify anti-MHC and
      anti-MLC antibodies, respectively, from an antiserum raised against Tetrahymena
      oral apparatus proteins. On western immunoblots of ATP-solubilized Tetrahymena
      proteins, the anti-MHC antibody detected a putative myosin heavy (180 kDa) chain,
      and the anti-MLC antibody detected a putative myosin light (18 kDa) chain. The
      anti-MHC antibody specifically labeled the AI zone of sarcomeres. In
      cosedimentation assays with an ATP-solubilized protein fraction, the 180 kDa
      polypeptide associated with skeletal muscle actin filaments in an ATP-dependent
      manner. The sedimented actin filaments appeared to be organized into bundles.
      Immunodepletion of the 180 kDa rendered the ATP-solubilized protein fraction
      ineffective in bundling actin filaments in a cosedimentation assay. ATP
      solubilized Tetrahymena proteins, which included the 180 kDa polypeptide,
      exhibited F-actin-stimulated, Mg2+ ATPase activity and K+, EDTA ATPase activity
      which are characteristic of myosin ATPases. Immunodepletion of the 180 kDa
      polypeptide reduced the F-actin, Mg2+ ATPase activity of the ATP-solubilized
      protein fraction by more than 80%. Based on these various observations, we
      conclude that the 180 kDa polypeptide is a putative myosin heavy chain, probably
      a myosin-II and that the 18 kDa polypeptide is probably a myosin-II light chain.
      We have used the affinity-purified, anti-myosin antibodies with
      immunofluorescence microscopy and immunogold electron microscopy to map the
      location of the putative myosin heavy and light chains in Tetrahymena.
      Immunofluorescence microscopy showed that the anti-myosin antibodies localized to
      Tetrahymena somatic and oral region basal bodies. At the ultrastructural level,
      the anti-myosin antibodies localized to filaments in the basal body-cage complex.
      The labeling patterns with both anti-myosin antibodies were identical to the
      labeling pattern observed with an anti-actin antibody reported in a previous
      study. The co-localization of myosin and actin argue for a motility system within
      the basal body-cage complex.

PMID- 7622615
TI  - A high molecular mass protein isolated from chicken gizzard: its localization at
      the dense plaques and dense bodies of smooth muscle and the Z-disks of skeletal
      muscle.
AB  - We purified a 450 kDa protein from a low-salt alkaline extract of chicken gizzard
      smooth muscle. This high molecular mass protein could be extracted with the low
      salt alkaline solution at 37 degrees C but not at 4 degrees C. The 450 kDa
      protein was isolated from the extract by ammonium sulfate fractionation and
      following sequential column chromatography using hydroxylapatite, DEAE
      Cellulofine A-800m and phenyl-Sepharose CL-4B resins. The partially purified
      protein molecule resembled a flexible rod with a globular head and an irregular
      shaped tail. Its length was approximately 300 nm. The nucleotide sequence of the
      partial cDNA encoding this protein was determined and analyzed with a data base.
      The analysis showed that the protein revealed significant homology with the rod
      region of chicken filamin (57% homology in amino acid sequence). Immunoblot
      analysis showed that an affinity-purified antibody reacted exclusively with the
      450 kDa protein band of smooth, skeletal and cardiac muscle tissues. By indirect
      immunofluorescence microscopy, we examined the localization of the 450 kDa
      protein in smooth and skeletal muscle cells. The affinity-purified antibody
      against the 450 kDa protein stained the dense plaques and dense bodies of smooth
      muscle, the peripheral region of Z-disks and the subsarcolemmal region of
      skeletal muscle. Immunoelectron microscopy confirmed the localization of the 450
      kDa protein at the peripheral regions of the actin anchoring structures mentioned
      above. Judging from its amino acid sequence, molecular size, molecular shape,
      immunological reactivity and localization in muscle cells, the 450 kDa protein
      seemed to be a new component associated with the actin-anchoring structures of
      muscle tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7622617
TI  - The topogenic fate of the polytopic transmembrane proteins, synaptophysin and
      connexin, is determined by their membrane-spanning domains.
AB  - The synaptophysins and connexins are polytopic transmembrane proteins of similar
      secondary structure that accumulate as multiple homo-oligomers in specialized
      membrane regions, the presynaptic transmitter vesicles or gap junctions.
      Transfection and expression of the respective genes in cultured epithelial cells
      results in the de novo formation of either small cytoplasmic, synaptophysin-rich
      vesicles, or functional gap junctions consisting of clustered connexin molecules.
      To examine the molecular requirements for the specific enrichment and topogenesis
      of both types of molecule, chimeric cDNAs were constructed composed of different
      parts of the rat synaptophysin and rat liver connexin32 genes. Expression of the
      encoded chimeric polypeptides in hepatocellular carcinoma-derived cells showed
      that only chimeras with all four transmembrane domains from either parent
      molecule were delivered to their specific destination. In contrast, chimeras with
      transmembrane domains from both connexin32 and synaptophysin were always retained
      in the endoplasmic reticulum. The topogenic nature of the transmembrane domains
      was further demonstrated by deletion mutagenesis, indicating that removal of
      cytoplasmic end domains or intravesicular loops does not abolish targeting. On
      the other hand, excision of individual transmembrane domains or introduction of
      point mutations in transmembrane segments resulted in retention in the
      endoplasmic reticulum.

PMID- 7622619
TI  - Role of the carboxyl-terminal Fib2 domain in fibronectin matrix assembly.
AB  - A truncated form of fibronectin consisting of the N-terminal 70 kDa and C
      terminal 37 kDa regions, designated r70F2, retained the ability to assemble into
      the extracellular matrix when expressed in cultured fibroblasts (Ichihara-Tanaka
      et al. (1992) FEBS Lett. 299, 155-158). To elucidate the role of the C-terminal
      37 kDa region in fibronectin matrix assembly, we expressed a panel of mutant
      forms of r70F2 with various deletions and amino acid substitutions in mouse L
      cells. Although substitution of Ser for two Cys residues in the C-terminal
      dimerforming segment led to a marked reduction in the matrix assembly activity of
      r70F2, the resulting monomeric r70F2 still retained a low, but significant
      activity to assemble into the matrix. Neither the N-terminal 70 kDa nor the C
      terminal 37 kDa regions, when expressed as monomeric forms, exhibited any
      residual activity, suggesting that the core domain of the 37 kDa region
      consisting of III15 and I10 through I12 modules, termed Fib2 domain, is actively
      involved in the matrix assembly of r70F2. In support of the role of Fib2 domain,
      the proteolytic fragment derived from the 37 kDa region inhibited the assembly of
      r70F2. Furthermore, en bloc deletion of the Fib2 domain or deletion of the I10
      through I12 modules from r70F2 resulted in a marked decrease of the matrix
      assembly activity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7622618
TI  - Fission yeast TPR-family protein nuc2 is required for G1-arrest upon nitrogen
      starvation and is an inhibitor of septum formation.
AB  - Fission yeast nuc2+ gene encodes a protein of a tetratricopeptide repeat (TPR)
      family which is conserved throughout evolution. We previously showed that nuc2 is
      required for exit from the mitotic metaphase. In this study, we present evidence
      which shows that nuc2 has two additional roles in the cell cycle. We showed that
      the nuc2 mutant is sterile even at the permissive temperature and septation
      occurs in the absence of chromosome separation at the restrictive temperature.
      The nuc2 mutant fails to arrest at the G1 phase upon nitrogen starvation at the
      permissive temperature which is a prerequisite for conjugation. Upon starvation,
      however, the nuc2 mutant ceased division normally and induced starvation
      dependent gene expression. Therefore, the nuc2 mutant is deficient only for
      failure to block DNA replication upon starvation. At the lower restrictive
      temperature, the nuc2 mutant showed a 'cut' phenotype where septation and
      cytokinesis takes place without the completion of mitosis. Ectopic overexpression
      of the nuc2+ gene caused multiple rounds of S and M phases in the complete
      absence of septum formation. We propose that nuc2 is a novel cell cycle regulator
      essential for three events; firstly for exit from mitosis, secondly for DNA
      replication restraint under nutrient starvation and thirdly for inhibition of
      septation and cytokinesis until the completion of mitosis.

PMID- 7622620
TI  - Liver-regulating protein (LRP) is a plasma membrane protein involved in cell
      contact-mediated regulation of Sertoli cell function by primary spermatocytes.
AB  - We have identified a liver-regulating protein involved in cell contact-mediated
      regulation of Sertoli cell function by primary spermatocytes in rat testis. Liver
      regulating protein was studied using monoclonal antibody L8 prepared from rat
      primitive biliary epithelial cells. This molecule was located in vivo at the
      interface of Sertoli cells and spermatocytes, and expressed in a stage-dependent
      manner (expression peaked on leptotene-zygotene spermatocytes). In vitro, the
      liver-regulating protein was found on Sertoli cell, spermatocyte and early
      spermatid membranes. Immunoaffinity procedures revealed two peptides of 85 and 73
      kDa for Sertoli cells, while spermatocytes and spermatids displayed a single
      smaller peptide of 56 kDa. The involvement of the liver-regulating protein in
      cell interaction-mediated regulation of Sertoli cell was assessed in vitro by
      tracing Sertoli cell transferrin and inhibin secretion, as well as mRNA synthesis
      in spermatocyte-Sertoli cell cocultures and in rat liver biliary epithelial cell
      Sertoli cell cocultures, performed in the presence or absence of monoclonal
      antibody L8. Inhibition of the spermatocyte- and liver biliary epithelial cell
      stimulated secretion of transferrin and inhibin by Sertoli cells was observed in
      the presence of antibody, whereas spermatocyte adhesiveness was unchanged. Using
      northern blot analysis, the steady state levels of transferrin mRNA decreased
      when the anti-liver-regulating protein antibody was added to the Sertoli cell
      spermatocyte cocultures or to the Sertoli cell-liver biliary epithelial cell
      cocultures. The data demonstrate the role of the liver-regulating protein in cell
      cell contact-mediated regulation of Sertoli function by primary spermatocytes and
      the important implications of this cell contact-dependent control in testicular
      activity.

PMID- 7622621
TI  - A murine replication protein accumulates temporarily in the heterochromatic
      regions of nuclei prior to initiation of DNA replication.
AB  - We have analyzed the expression of the murine P1 gene, the mammalian homologue of
      the yeast MCM3 protein, during the mitotic cell cycle. The MCM3 protein has
      previously been shown to be of importance for initiation of DNA replication in
      Saccharomyces cerevisiae. We found that the murine P1 protein was present in the
      nuclei of mammalian cells throughout interphase of the cell cycle. This is in
      contrast to the MCM3 protein, which is located in the nuclei of yeast cells only
      between the M and the S phase of the cell cycle. Detailed analysis of the
      intranuclear localization of the P1 protein during the cell cycle revealed that
      it accumulates transiently in the heterochromatic regions towards the end of G1.
      The accumulation of the P1 protein in the heterochromatic regions prior to
      activation of DNA replication suggests that the mammalian P1 protein is also of
      importance for initiation of DNA replication. The MCM2-3.5 proteins have been
      suggested to represent yeast equivalents of a hypothetical replication licensing
      factor initially described in Xenopus. Our data support this model and indicate
      that the murine P1 protein could function as replication licensing factor. The
      chromosomal localization of the P1 gene was determined by fluorescence in situ
      hybridization to region 6p12 in human metaphase chromosomes.

PMID- 7622622
TI  - Glycolipid migration from the apical to the equatorial subdomains of the sperm
      head plasma membrane precedes the acrosome reaction. Evidence for a primary
      capacitation event in boar spermatozoa.
AB  - In order to extend the static information of immunolabelling sulphogalactolipids
      in fixed boar spermatozoa, a fluorescent sulphogalactolipid analogue, galactose(3
      sulphate)-beta 1-1'[(N-lissamine rhodaminyl)-12-aminodode-canoyl]-sphingosine,
      was incorporated into plasma membranes of living spermatozoa and its lateral
      distribution over the sperm head was studied. The fluorescent lipid was enriched
      in the apical ridge subdomain of freshly ejaculated sperm cells. After sperm
      binding to the zona pellucida the lipid redistributed to the equatorial segment
      of the sperm surface. A similar shift occurred during capacitation in vitro with
      2 mM CaCl2 or with 4% (w/v) bovine serum albumin. The desulphated derivative
      galactose-beta 1-1'[(N-lissamine rhodaminyl)-12-aminododecanoyl]-sphingosine was
      also incorporated into the plasma membrane of freshly ejaculated sperm cells and
      clearly stained the apical ridge subdomain and the (pre)-equatorial subdomains of
      the sperm heads. The desulphogalactolipid analogue showed a slightly faster
      migration to the equatorial segment of the sperm plasma membrane than did its
      sulphated counterpart. The measured fluorescence intensity distributions
      correlated linearly with the spatial probe distribution, which was checked by
      fluorescence lifetime imaging microscopy. The observed migration of the
      incorporated glycolipids precedes the acrosome reaction and is one of the
      underlying molecular events likely to be important in the process of sperm
      capacitation. The results of this study suggest that lipid phase segregation is
      an important driving force for the organization of the sperm head plasma membrane
      into subdomains.

PMID- 7622623
TI  - Phagocytosis of apoptotic bodies by liver endothelial cells.
AB  - Using electron microscopy and cytofluorimetry we studied the role of carbohydrate
      specific recognition systems in the interaction of apoptotic bodies with normal
      and interleukin 1-activated sinusoidal endothelial cells. Microfluorimetric
      observation of liver tissue sections revealed octadecylrhodamine B-labelled
      apoptotic body binding to the sinusoidal wall of mouse liver, when they were
      injected intraportally. Plate-scanning cytofluorimetry demonstrated that about 20
      25% of Acridine Orange-labelled apoptotic bodies could adhere specifically to
      cultured endothelial cells after 15 minutes of incubation. Adhesion increased to
      30% when the cells were incubated for 60 minutes. Using a mixture of galactose/N
      acetylglucosamine/mannose as competition solution apoptotic body adhesion was
      significantly reduced especially after longer times of incubation, when the
      percentage of inhibition reached 50%. Following 4 hours exposure of liver
      endothelial cells to 1 ng/ml human recombinant interleukin-1 beta adhesion
      markedly increased after 60 minutes of incubation, whereas the co-incubation of
      interleukin-1 beta with the inhibitors brings down the adhesion to basal values
      obtained in controls. Electron microscopic observation of the adhesion process
      showed that the number of endothelial cells binding apoptotic bodies gradually
      increased from low to high values with time. After 60 minutes of incubation, the
      majority of apoptotic bodies were seen inside phagosomes and only a few remained
      at the cell surface. Liver endothelial cells bound and endocytosed apoptotic
      bodies through carbohydrate-specific receptors. Moreover, this scavenger action
      was interleukin-1 enhanced, thus suggesting its possible activation during
      inflammatory and immune processes.

PMID- 7622624
TI  - Alpha v and alpha 3 integrin subunits are associated with myofibrils during
      myofibrillogenesis.
AB  - The development of the myofibrillar apparatus in skeletal muscle is a process in
      which transmembrane linkages with adhesion molecules are implicated. Integrins
      are one class of transmembrane adhesion receptors which appear to mediate these
      interactions. Two prominent linkages are at the myotendinous junction (MTJ),
      which residues at the ends of the cell and connects myofibrils to the tendon, and
      the costameres, which encircle the girth of the cell and connect the Z-disks to
      the sarcolemma. In this study we report that the alpha v integrin subunit is a
      prominent component of the costamere. The alpha v subunit is present initially on
      developing myotubes in a diffuse staining pattern with some concentration along
      nascent myofibrils. However, it appears in a striated pattern at the costamere
      and inconsistently at the M-line following the striation of alpha-actinin and
      titin but before that of desmin. Its recruitment to preformed striation suggests
      that it is incorporated into a pre-existing structure. The presence of alpha v in
      the costamere points to a role in lateral myofibrillar anchorage. In addition, we
      find that the alpha 3 subunit is transiently associated with myofibrils along
      portions of their lengths and at their ends during myofibrillogenesis. The alpha
      3 subunit staining shows a novel localization and junctional structure. As
      myofibrils become striated the alpha 3 integrin dissociates from the localized
      pattern and becomes diffuse. This suggests a possible role in the stabilization
      of nascent myofibrils prior to striation. Antibody-induced perturbation of
      adhesion mediated by the integrin beta 1 subunit in developing myotubes inhibits
      assembly of the sarcomeric architecture.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7622625
TI  - Rabbit skeletal muscle alpha alpha-tropomyosin expressed in baculovirus-infected
      insect cells possesses the authentic N-terminus structure and functions.
AB  - When expressed in E. coli, skeletal muscle alpha-tropomyosin has an unacetylated
      N-terminus. Unacetylated alpha-tropomyosin lacks important functions; this is non
      polymerizable and has a low affinity to actin. In the present work, in order to
      obtain fully functional recombinant alpha-tropomyosin, rabbit skeletal muscle
      alpha-tropomyosin (alpha-tropomyosin BV) has been expressed in baculovirus
      infected insect cells. alpha-TropomyosinBV was not distinguishable from the
      authentic tropomyosin, not only in functional properties but also in blocked N
      terminus. To know the N-terminus structure of alpha-tropomyosinBV, the N-terminal
      segment six amino acids long, MDAIKK, has been specifically and efficiently
      removed from alpha-tropomyosinBV by use of an immobilized proteolytic enzyme
      system based on E. coli cell bodies which carry the ompT gene product, a
      proteolytic enzyme localized on the outer cell wall of E. coli. The structure of
      recombinant alpha-tropomyosinBV was shown to be identical to the authentic
      protein by electrospray mass spectrometry and protein sequencing analysis.
      Additionally, electrospray mass spectrometry indicated a single phosphorylation
      not only in alpha- but also beta-tropomyosin chains in the rabbit skeletal
      muscle. The differentiated susceptibilities of potential ompT cleavage sites are
      indicative of a non-coiled-coil conformation of the N-terminus of alpha
      tropomyosin.

PMID- 7622626
TI  - Adaptation in myosin expression of avian skeletal muscle after weighting and
      unweighting.
AB  - Stretch-induced hypertrophy of the quail anterior latissimus dorsi is associated
      with decreased slow myosin 1 and increased slow myosin 2 expression and a small
      increase in expression of fast myosins. Because reduced neural activity has also
      been shown to accelerate expression from slow myosin 1 to slow myosin 2, we
      tested whether the increased expression of slow myosin 2 would be maintained when
      stretch was removed during a time when muscle activity would not be expected to
      increase. Quail anterior latissimus dorsi muscles were examined after 0-30 days
      of stretch overload and after 30 or 60 days of unweighting following 30 days of
      stretch. As expected, slow myosin 2 expression increased and slow myosin 1
      expression decreased after 14-30 days of stretch. Novel findings were that slow
      myosin 1 and slow myosin 2 returned to control levels after unweighting.
      Furthermore, the expression of developmental and fast myosin heavy chains were
      evident by day 7, and maintained throughout wing unweighting. These data are
      consistent with the hypothesis that alterations in fast and developmental myosin
      expression result from formation and subsequent maintenance of new fibres during
      hypertrophy and regression. The relative amount and expression of myosin appears
      dependent upon mechanical stretch in the anterior latissimus dorsi muscle.

PMID- 7622627
TI  - DNase I interaction on muscle Z-line.
AB  - The effect of deoxyribonuclease I on muscle Z-line structures was re-examined.
      Under conditions of deoxyribonuclease I activation (presence of the divalent
      cation Ca2+ and Mg2+), a deoxyribonuclease I preparation did not affect Z-line
      structure if phenylmethylsulfonylfluoride, an inhibitor of serine proteases, was
      also present. In the absence of protease inhibitor, both Z-lines and M-lines were
      digested, even in the presence of EDTA and EGTA as inhibitors of
      deoxyribonuclease I. These electron microscopic observations were consistent with
      the following results from sodium dodecyl sulphate gel electrophoresis: when the
      protease was inhibited but deoxyribonuclease I was activated, myofibrillar
      proteins remained essentially intact. However, degradation of proteins in both
      rabbit psoas and chicken pectoralis myofibrils was observed in the presence of
      deoxyribonuclease I inhibitors when the protease inhibitor was absent. Our data
      strongly suggest that the interaction of deoxyribonuclease I with Z-line proteins
      previously reported is most likely due to contamination of the deoxyribonuclease
      I fraction by the serine-type proteases.

PMID- 7622628
TI  - Inhibition of unloaded shortening velocity in permeabilized muscle fibres by
      caged ATP compounds.
AB  - The effects of both the P3-1-(2-nitrophenyl)ethyl ester of adenosine 5'
      triphosphate (NPE-caged ATP) and its separate diastereoisomers, and the P3-3',5'
      dimethoxybenzoin ester of ATP (DMB-caged ATP) were studied on the unloaded
      shortening velocity of glycerinated rabbit psoas muscle fibres. The unloaded
      shortening velocities of the active fibres were measured as a function of ATP
      concentration (0.1-5 mM) using the 'slack-test' with and without 2 mM caged ATP.
      Shortening velocity followed a Michaelis-Menten relationship with ATP
      concentration, the Km for ATP being 170 microM. The caged ATP compounds inhibited
      shortening velocity, in a manner consistent with competitive inhibition, with a
      Ki of 1-2 mM. The R- and S-diastereoisomers of NPE-caged ATP showed the same
      degree of competitive inhibition of the shortening velocity, as did DMB-caged
      ATP. These observations suggest that caged ATP compounds bind to the ATPase site
      of the actomyosin where they compete with the substrate, Mg2+ ATP.

PMID- 7622629
TI  - On the hand-over-hand footsteps of kinesin heads.

PMID- 7622630
TI  - Selection for rapid growth increases the number and the size of muscle fibres
      without changing their typing in chickens.
AB  - Quantitative (muscle fibre number and cross-sectional areas) and qualitative
      (myosin isoforms and metabolic enzyme activities) characteristics of two muscles,
      M. pectoralis major and M. anterior latissimus dorsi, were compared among male
      chickens of two lines during growth from hatching to adulthood. The lines were
      derived from a divergent selection based on growth rate. The two muscles were
      chosen on the basis of their histochemical profile. Pectoralis major muscle
      contains only fast contracting muscle fibres whereas anterior latissimus dorsi
      muscle is almost entirely made up with slow contracting fibres. At both ages, the
      two lines showed similar fibre type distributions. At hatching, fibre cross
      sectional areas were equivalent in the two lines, but after the first week,
      animals from the fast growing line exhibited wider fibre areas, whatever the
      muscle, than animals from the slow growing line. The total number of fibres in a
      muscle was found greater in the fast growing line, irrespective of whether it was
      exactly determined (anterior latissimus dorsi muscle, + 20%) or only estimated
      (pectoralis major muscle). This number remains constant in the two lines
      throughout the growth. Myosin isoform profiles and metabolic enzyme activities
      were similar in the two lines, at both ages, and were in good agreement with the
      histochemical muscle fibre profiles.

PMID- 7622631
TI  - Calcium and other salivary factors in periodontitis-affected subjects prior to
      treatment.
AB  - Salivary calcium was shown to be higher in treated periodontitis-affected
      subjects (P+) than in periodontitis-free patients (P-). Here the aim was to study
      whether differences in calcium or other salivary factors exist prior to
      treatment. The test group consisted of 20 (15 men, 5 women) periodontitis
      affected subjects and the control group 15 subjects (10 men, 5 women) free from
      periodontitis. Paraffin-stimulated whole saliva was collected to determine the
      flow-rate, calcium and phosphate concentrations, pH, buffering capacity, numbers
      of mutans streptococci, lactobacilli and yeasts. The results showed a higher
      calcium concentration (p < 0.05) in the P+ group (mean: 1.68 mmol/l; SE: 0.06 in
      men and mean: 1.49 mmol/l; SE: 0.10 in women) than in the P-group (mean: 1.48
      mmol/l; SE: 0.09 in men and mean: 1.18 mmol/l; SE: 0.10 in women). The P+ group
      had more intact teeth (mean +/- SE: 9.9 +/- 0.8 in men and 11.2 +/- 2.0 in women)
      than the P-group (mean +/- SE: 8.3 +/- 0.7 in men and 8.2 +/- 2.4 in women). The
      present findings may indicate that an elevated level of salivary Ca is
      characteristic of P+ patients both before and after periodontal treatment.

PMID- 7622632
TI  - Single-blind studies of the effects of improved periodontal health on metabolic
      control in type 1 diabetes mellitus.
AB  - Uncontrolled studies have suggested a beneficial effect of periodontal treatment
      on metabolic control of insulin-dependent diabetes mellitus (IDDM). We therefore
      conducted controlled single-blind studies, using current metabolic status
      indicators in IDDM subjects free of significant complications other than
      periodontal diseases. In the 1st study, 41 IDDM subjects with gingivitis and
      early periodontitis were randomly assigned to treatment (oral hygiene and
      scaling) or control groups. The study was completed by 16 experimental and 15
      control subjects. Reassessment after 2 months showed a Hawthorne effect in the
      control group, and no difference between groups. However, further analysis showed
      a relationship between individual metabolic control variation and gingival
      inflammation. A 2nd study enrolled 23 IDDM subjects with advanced periodontitis,
      who were randomised to treatment (full initial therapy including root planning)
      or control groups. Only 1 subject failed to complete the study, owing to illness.
      In this study, a significant response to periodontal treatment was not
      accompanied by any improvement in metabolic control. These results support the
      concept that the effect of metabolic control may be predominant in the
      relationship between IDDM and periodontal health.

PMID- 7622633
TI  - The effect of flap management and bioresorbable occlusive devices in GTR
      treatment of degree III furcation defects. An experimental study in dogs.
AB  - The present experiment on guided tissue regeneration had 2 objectives namely: (i)
      to study if an improved anchorage of the soft tissue flaps during the initial
      healing period after membrane placement would reduce the tendency for soft tissue
      recession and allow for healing of also large furcation defects; (ii) to
      determine if the use of biodegradable membranes in GTR procedures may promote new
      attachment formation in degree III furcation defects. 2 experiments were
      performed which included 5 and 8 dogs each. In each animal, the 3rd premolar of
      the left or right side of the mandible was selected as test site using the
      contralateral tooth as control. 2 months prior to the start of the experiment,
      the 2nd and 4th premolars in each side of the mandible were extracted. The
      extractions were performed to create a large edentulous space mesial and distal
      to the 3rd premolar. During GTR therapy the incisions prepared in this edentulous
      region were used to allow proper suture retention and flap stability during the
      initial phase of healing. In study 1, furcation defects (degree III) were
      prepared and subsequently treated according to GTR using e-PTFE membranes in the
      test and no membrane in the control site. In study 2, a bioresorbable membrane
      (Resolut) was installed in the test and an e-PTFE membrane in the control sites.
      The non-resorbable membranes were removed after 30 days. The animals were
      sacrificed 5 months after reconstructive surgery, biopsies were harvested,
      sectioned and analyzed histologically for new connective tissue attachment and
      bone.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7622634
TI  - Increased collagen degradation by experimentally-induced granulation tissue
      inoculated with bacteria.
AB  - Periodontitis is characterized by asymptomatic periodic collagen degradation,
      which is accompanied by the formation of granulation tissue induced by bacteria.
      The lesions sometimes contain micro-organisms and/or micro-abscesses that are of
      unknown significance. The aim of this study was to determine whether bacteria in
      a sterile granulation tissue could enhance its collagenolytic capacity. The
      formation of granulation tissue was induced by implanting a cellulose sponge in
      the subcutaneous tissue in the back of the rat. Bacteria were injected every
      other day into the sponge from day 8 to day 18. The cell-dependent degradation of
      a homologous 3H-collagen powder enveloped in the sponge was measured by the
      radioactivity of the urine excreted 8-18 days after the implantation. The
      injections increased the excretion of radioactivity by about 40% compared with
      the controls (n = 8, p < or = 0.005), but caused no clinical signs of acute
      infection or inflammation. On day 18, 2 days after the last injection of
      bacteria, no bacteria or increased cell infiltration were observed in the
      granulation tissue. The appearance of the latter could not be distinguished from
      that of the control tissues injected with buffer alone. It seems reasonable to
      assume that the increased collagen degradation results from enhanced activity of
      phagocytes, which may also be related to an increased release of tissue
      destructive proteases and free oxygen radicals into the extracellular space. In
      conclusion, brief recurrent episodes of bacteria in granulation tissue can
      increase its collagen degrading-capacity. The latter may be due to augmented cell
      activity in the tissue. This response seems to have some features comparable to
      the pathogenesis of episodic periodontitis, e.g., by mimicking the collagen
      degradation.

PMID- 7622635
TI  - Healing of lichenoid reactions following removal of amalgam. A clinical follow
      up.
AB  - 174 patients referred to the Department of Oral and Maxillofacial Surgery,
      Central Hospital, Karlstad, Sweden during 1987 to 1989 for lichenoid lesions and
      evaluation of a possible connection with amalgam restorations were invited to a
      clinical re-examination. 159 of the patients were re-examined with the purpose of
      evaluating the long-term effect upon performed substitution therapy. Partial or
      total removal of amalgam had been recommended according to a set of given
      criteria. The re-examination showed that 62 patients had performed partial and 69
      patients total removal of amalgam fillings. 28 patients had not performed any
      substitution therapy. There was a difference between recommended and performed
      therapy. The results demonstrated that 92% of patients with lichenoid lesions
      only in contact with amalgam fillings healed or improved clinically following
      removal of amalgam. No statistical difference was found in healing between
      patients who only removed fillings in contact and those who had removed all
      amalgam restorations. More than 60% of buccal lichenoid lesions without contact
      with amalgam at time of referral disappeared following amalgam substitution.
      Gingival lichenoid lesions did not respond to substitution of amalgam to another
      material. 3 out of 17 patch-tested patients demonstrated a hypersensitivity
      reaction to mercury. All lichenoid lesions in these patients healed following
      total substitution. Partial or total removal of amalgam fillings was also
      performed on 10 patients with completely negative patch-tests. 6 out of these
      patients demonstrated complete healing of their lichenoid reactions at re
      examination.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7622636
TI  - New attachment and bone formation in periodontal defects following treatment of
      submerged roots with guided tissue regeneration.
AB  - The purpose of the present study was to examine the effect on periodontal
      regeneration of preventing bacterial contamination of the membrane material
      following the guided tissue regeneration procedure (GTR). Periodontal dehiscence
      defects were surgically produced in 2 monkeys. In each monkey, 8 of these defects
      were submerged after resection of the crowns of the teeth and a teflon (Gore-Tex
      Periodontal Material) or a polyglactin (Vicryl Mesh) membrane was adjusted to
      cover the defect and the exposed root surface. 4 defects on non-crown resected
      teeth were treated with either a teflon or a polyglactin membrane positioned with
      the coronal border approximately 2 mm below the margin of the covering tissue
      flap. Following 6 months of healing, the animals were sacrificed. Histological
      evaluation of the specimens revealed that roots which were kept completely
      covered during the healing period demonstrated new connective tissue attachment
      and bone formation corresponding to 67-100% of the length of the initial defect
      depth, whereas the amount of new connective tissue attachment and bone on non
      submerged roots ranged between 30-59% and 11-31%, respectively. It seems
      reasonable to anticipate that it is bacterial contamination of the membrane
      material which jeopardizes the formation of new connective tissue attachment but
      in particular bone formation following the GTR-procedure.

PMID- 7622637
TI  - Correlation of the periodontal status 6 years after puberty with clinical and
      microbiological conditions during puberty.
AB  - The purpose of this study was to assess the oral clinical and microbiological
      status of young adults 6 years after puberty and to compare these findings with
      the conditions observed during puberty. Clinical and microbiological parameters
      were monitored in 42 individuals 10 x between the ages of 11 and 14 years. 33
      individuals were re-examined 10 years after the start of this monitoring.
      Microbiology included 2 subgingival samples per subject taken from the
      mesiobuccal aspects of the upper 1st molars. The samples were subject to
      continuous anaerobic culturing. Individuals with a marked and sustained increase
      in mean papillary bleeding scores during puberty (group A, n = 16) differed 6
      years later from individuals without pronounced puberty gingivitis (group C, n =
      8) in several aspects. Individuals in group A had a significantly higher gingival
      bleeding tendency and an increased number of sites with more than 3 mm attachment
      loss. The subjects in group C showed the lowest anaerobic total cultivable
      counts. Spirochetes were detected only in group A subjects (4 samples in 3
      individuals). In all positive sites, spirochetes had been identified at least 8
      out of 10 times during puberty. A. actinomycetemcomitans was present in only one
      individual of group A. P. gingivalis had not been detected during puberty; none
      of the samples were P. gingivalis positive 6 years later. P. intermedia was found
      in 27% of all samples, isolates belonging to the P. melaninogenica group of black
      pigmenting anaerobes had a frequency of 6%, 6 years after puberty.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7622638
TI  - Clinical and radiographical split-mouth-study on resorbable versus non-resorbable
      GTR-membranes.
AB  - The aim of this prospective split-mouth-study was to compare the 5-months-healing
      results after implantation of resorbable (Polyglactin-910) and non-resorbable (e
      PTFE) GTR-membranes. 12 healthy patients with 41 periodontal defects were
      treated. Radiographical and clinical examinations (papillary bleeding index,
      gingival recession, probing pocket depth, probing attachment level, and furcation
      depth) were carried out under standardized conditions immediately before and 5
      months after surgery. The vertical relative attachment gain (V-rAG) was
      calculated as a % of the bony defect depth (intra-operatively measured) at
      baseline, and the horizontal relative attachment gain (H-rAG) as a % of the
      furcation depth at baseline. The standardized radiographs were evaluated blind by
      4 experienced examiners for changes of the alveolar bone. Furthermore, digital
      subtraction radiography was carried out using the standard deviation of the grey
      level histograms in the experimental region and in a control region as a test
      parameter for bone changes. Both types of membranes achieved an attachment gain.
      Using the split-mouth-design, no statistically significant (< or = 0.05)
      difference between the two membranes could be detected (number of defects/median)
      with regard to V-rAG (Polyglactin: 12/77.5%, e-PTFE: 12/73.2%) or to H-rAG of
      class-II-furcations (Polyglactin: 5/66.7%, e-PTFE: 5/66.7%), or to bone changes
      using conventional and subtraction radiographic evaluation. In conclusion based
      on this 5-months-study, the resorbable membranes provided attachment gain
      comparable to the e-PTFE-membranes.

PMID- 7622639
TI  - Microbiological features of gingivitis in pubertal children.
AB  - The subgingival microflora of 42 pubertal children (aged 12-15 years) and 18
      young adults (aged 21-25 years) was investigated by anaerobic culture and phase
      contrast microscopy. Motile rods, spirochetes and Prevotella intermedia were
      elevated proportionately in pubertal children with gingivitis (median GI > or =
      1); however, no statistically significant differences in enumerated organisms on
      selective media were observed between pubertal children and young adults. These
      organisms were positively correlated with the index of bleeding on probing and
      the gingival index of pubertal children. Pubertal children were divided into 3
      distinct subject clusters according to the similarity of subgingival microbial
      features, and the subjects who were then selected for the gingivitis group were
      distributed into clusters 1 and 2. The proportions of motile rods, P. intermedia
      and Eikenella corrodens were significantly higher in cluster 2 than in cluster 1.
      These results suggest that these 2 species and motile rods which differentiated
      features of clusters, are useful for screening of high-risk subjects for
      worsening of inflammation.

PMID- 7622640
TI  - Bacterial penetration in vitro through GTAM membrane with and without topical
      chlorhexidine application. A light and scanning electron microscopic study.
AB  - Premature exposure of membrane in the oral cavity is considered the most common
      complication as well as a reason for failure or incomplete success of guided
      tissue regeneration, as the exposed membrane undergoes plaque accumulation. A
      method to control, or at least to reduce the bacterial invasion of the membrane
      allowing a delay in the membrane removal, could be of clinical interest. The
      purpose of the present study was to evaluate the possibility of treating, with
      topical chlorhexidine application, the bacterial colonization of exposed
      membranes. A special device was developed in order to evaluate, under an
      experimental environment, the bacterial colonization. This device was made from a
      removable acrylic denture base to which 5 gold cups were attached. The cups
      consisted of an internal compartment, isolated from the oral cavity by a GTAM
      membrane, and an external compartment exposed to the oral environment. 3 healthy
      subjects had this device fitted, bilaterally, in the molar-premolar region of the
      upper jaw. The cups of one side of each subject had 0.2% chlorhexidine gluconate
      gel applied 2x a day for 1 min, whereas those of the other side served as
      controls. 12 cups were removed after 2 weeks and the remainder removed after 1
      month. The non-treated control specimens were characterized by greater amounts of
      plaque accumulation. In all the test sites, plaque deposits increased in
      thickness and quantity during the 4 weeks of the experiment. Complete invasion of
      the membrane and initial colonization of its internal surface were observed only
      in 4-week specimens. A relatively simple flora consisting mainly of cocci and
      short rods, was found in bacterial deposits forming under the influence of
      chlorhexidine, whereas in non-treated specimens, it was possible to observe a
      more mature and complex plaque, composed mostly of filamentous bacteria. In
      conclusion, topical application of chlorhexidine gel is an effective method of
      reducing plaque and calculus formation on the surface of GTAM membranes exposed
      to the oral cavity for up to 4 weeks. This study has, however, failed to
      demonstrate the capacity of chlorhexidine to prevent or to retard bacterial
      penetration through the thickness of the inner portion of the membranes.

PMID- 7622641
TI  - Healing of periodontal lesions in monkeys following the guided tissue
      regeneration procedure. A histological study.
AB  - The purpose of the present investigation was to study histologically the healing
      of periodontal lesions in monkeys during the first 9 weeks following periodontal
      reconstructive surgery according to the principle of guided tissue regeneration.
      Horizontal interproximal lesions and through-and-through bifurcation defects were
      surgically produced in 2 adult monkeys. Following removal of granulation tissue
      and root planing, notches indicating the level of the reduced bone level were
      prepared in the root surfaces. Sterile teflon membranes were then adjusted to
      cover the defects, and the gingival flaps were sutured in a coronally displaced
      position. Sacrifice of the animals was scheduled to allow for observation periods
      of 1, 3, 4 and 9 weeks. Evaluation of histological specimens revealed a
      continuous growth of new connective tissue during a period of 4 weeks. The
      coronal growth of new tissue did not increase significantly between 4 and 9
      weeks. New cementum had formed in the most apical part of one notch after 1 week
      of healing, and following 3 and 4 weeks, new cementum with inserting periodontal
      ligament fibers were observed in all notches and to a varying degree, also more
      coronally on the root surfaces of both interproximal and bifurcation defects.
      Limited regrowth of alveolar bone was observed in the 9-week specimens. Judged
      from the course of the blood vessels within the newly formed connective tissue in
      the defects, the tissue in the central part of the defects had originated from
      the alveolar bone, whereas the tissue adjacent to the root surfaces seemed to
      have its origin in the residual periodontal ligament.

PMID- 7622642
TI  - Cutaneous metastatic disease.
AB  - The relative frequencies of cutaneous metastases are similar to those of the
      primary cancers; breast, colon, and melanoma are the most frequent in women and
      lung, colon, and melanoma are the most common in men. Cutaneous metastases
      represent an opportunity to detect a potentially treatable cancer before other
      evidence of it is present, to modify therapy as appropriate to the tumor stage,
      or possibly to use the cutaneous lesion as a source of easily accessible tumor
      cells for specific therapy. Cutaneous metastatic disease as the first sign of
      internal cancer is most commonly seen with cancer of the lung, kidney, and ovary.

PMID- 7622643
TI  - Unusual specific cutaneous lesions in myelodysplastic syndromes.
AB  - BACKGROUND: Early diagnosis of leukemia cutis in myelodysplastic syndrome (MDS)
      is important because these lesions can precede acute peripheral blood or bone
      marrow transformation. Leukemia cutis is usually easy to recognize, but atypical
      lesions are not well described. OBJECTIVE: Our purpose was to describe unusual
      specific lesions in MDS. METHODS: Data from patients with myeloid malignancies
      and leukemia cutis were reviewed. Only patients with MDS and cutaneous lesions
      different from typical tumors were included. Clinical features were analyzed.
      RESULTS: Four patients with MDS and unusual specific cutaneous lesions were
      found. They had ecchymoses, necrotic plaques or ulcers, and prurigo-like lesions.
      In three of four patients appearance of these skin lesions heralded or was
      concomitant with acute transformation. CONCLUSION: Specific cutaneous lesions can
      display unusual patterns. Early biopsy of cutaneous lesions in MDS is indicated.

PMID- 7622645
TI  - Familial cutaneous cylindromas: investigations in five generations of a family.
AB  - BACKGROUND: Multiple cutaneous cylindromas are probably inherited in an autosomal
      dominant way. OBJECTIVE: Our purpose was to describe a large family with
      cutaneous cylindromas, trichoepitheliomas, and milia occurring in five
      generations and to elucidate further the mode of inheritance. METHODS: We
      examined 39 family members and obtained information on 31 other members from
      reports of relatives. RESULTS: The pedigree included 237 members, 118 male and
      119 female, with 30 affected patients (11 male, 19 female). Between 33% and 100%
      of the children of affected family members had one or more of these skin lesions.
      Female-to-female, female-to-male, male-to-female, and male-to-male inheritance
      occurred. CONCLUSION: Multiple cutaneous cylindromas are inherited in an
      autosomal dominant way with variable clinical expression. Penetrance reaches 100%
      in adult life. This condition is associated with trichoepitheliomas and milia.

PMID- 7622644
TI  - Cetirizine and astemizole therapy for chronic idiopathic urticaria: a double
      blind, placebo-controlled, comparative trial.
AB  - BACKGROUND: Cetirizine and astemizole have been shown to be safe and effective in
      the treatment of patients with chronic idiopathic urticaria. Cetirizine brings
      about clinical benefit more rapidly. OBJECTIVE: The purpose of this study was to
      compare the efficacy of single daily doses of cetirizine and astemizole in
      relieving the symptoms of chronic idiopathic urticaria, with particular emphasis
      on the commencement of action. METHODS: Patients with chronic idiopathic
      urticaria were randomly assigned to relieve either 10 mg of cetirizine, 10 mg of
      astemizole, or placebo for 4 weeks in a multicenter double-blind trial. Patients
      rated symptom severity each night, and investigators rated symptoms weekly.
      RESULTS: One hundred eighty-seven patients were enrolled in the trial; 180 were
      included in the safety analysis and 177 were included in at least one efficacy
      analysis. Both cetirizine and astemizole were significantly superior to placebo
      in relieving symptoms of chronic idiopathic urticaria. Both patients' and
      investigators' ratings indicated that cetirizine acted more rapidly. Both active
      treatments were well tolerated, and the incidence of somnolence did not differ
      statistically between cetirizine (14.5%) and astemizole (10.3%). CONCLUSION: Both
      cetirizine and astemizole provide effective relief of the symptoms of chronic
      idiopathic urticaria with similar side-effect profiles. However, clinical benefit
      occurs significantly more rapidly with cetirizine.

PMID- 7622646
TI  - Prevalence of cutaneous findings in hospitalized medical patients.
AB  - BACKGROUND: Cutaneous signs may represent a systemic process or a primary
      cutaneous disorder. Prompt observation and identification of cutaneous
      abnormalities should improve care of hospitalized medical patients. OBJECTIVE:
      Our purpose was to determine the prevalence of cutaneous abnormalities in newly
      hospitalized medical patients and the frequency with which these findings were
      noted by the admitting team. METHODS: All new medical patients were offered a
      complete skin examination within 48 hours after admission to the hospital, and
      231 participated. Cutaneous diagnoses were based on characteristic clinical
      features or skin biopsy in patients in whom a diagnosis could not be made
      clinically. RESULTS: Ninety-three cutaneous findings were present in 83 (35.9%)
      of 231 patients. In 31 (13.4%) we found cutaneous signs related to the reason for
      hospitalization or associated with a systemic disorder. These were not noted by
      the admitting medical service in 14 patients. In two patients, one with
      metastatic adenocarcinoma and one with sclerosis, the cutaneous findings were
      manifestations of the new diagnosis. In 52 patients (22.5%) we found 62 primary
      cutaneous disorders. Fifty-eight disorders (93.5%), including 10 nonmelanoma skin
      cancers, were unrecognized at the time of admission. CONCLUSION: Cutaneous
      findings representative of systemic disease or primary cutaneous disorders are
      commonly present and frequently overlooked in medical patients newly admitted to
      the hospital. These data suggest that a complete skin examination is necessary in
      all newly hospitalized medical patients.

PMID- 7622647
TI  - Prevention of poison ivy and poison oak allergic contact dermatitis by quaternium
      18 bentonite.
AB  - BACKGROUND: Poison ivy and poison oak are the most common causes of allergic
      contact dermatitis in North America. OBJECTIVE: We investigated whether a new
      topical lotion containing 5% quaternium-18 bentonite prevents experimentally
      induced poison ivy and poison oak allergic contact dermatitis. METHODS: A single
      blind, paired comparison, randomized, multicenter investigation was used to
      evaluate the effectiveness and safety of quaternium-18 bentonite lotion in
      preventing experimentally induced poison ivy and poison oak allergic contact
      dermatitis in susceptible volunteers. One hour before both forearms were patch
      tested with urushiol, the allergenic resin from poison ivy and poison oak, 5%
      quaternium-18 bentonite lotion was applied on one forearm. The test patches were
      removed after 4 hours and the sites interpreted for reaction 2, 5, and 8 days
      later. The difference in reactions between treated and untreated patch test sites
      was statistically analyzed. RESULTS: Two hundred eleven subjects with a history
      of allergic contact dermatitis to poison ivy and poison oak were studied. One
      hundred forty-four subjects had positive reactions to urushiol. The test sites
      pretreated with quaternium-18 bentonite lotion had absent or significantly
      reduced reactions to the urushiol compared with untreated control sites (p <
      0.0001) on all test days. When it occurred, the reaction consistently appeared
      later on treated than on control sites (p < 0.0001). One occurrence of mild,
      transient erythema at the application site was the only side effect from the
      quaternium-18 bentonite lotion. CONCLUSION: Quaternium-18 bentonite lotion was
      effective in preventing or diminishing experimentally produced poison ivy and
      poison oak allergic contact dermatitis.

PMID- 7622648
TI  - Topical hydrogen peroxide treatment of ischemic ulcers in the guinea pig: blood
      recruitment in multiple skin sites.
AB  - BACKGROUND: Oxygen deficit is a key factor associated with delayed healing of
      ischemic wounds in human beings. Topical oxygen-releasing compounds such as
      hydrogen peroxide or tetrachlorodecaoxide have been suggested as therapy for
      ischemic tissue. OBJECTIVE: Our purpose was to monitor the effect of hydrogen
      peroxide cream on the process of ischemic ulcer healing with a model for ischemic
      ulcers in the guinea pig. METHODS: Measurement of vascular perfusion with a laser
      Doppler velocimeter and gross observations of percentage of nonnecrotic wound
      surface were made on ischemic wounds in guinea pigs after treatment with either a
      hydrogen peroxide cream or a placebo cream. RESULTS: Visual evaluations of the
      percentage of nonnecrotic wound surface showed no statistically significant
      differences among the treatments. In contrast, vascular perfusion measurements
      resulted in statistically significant differences. Blood flow was significantly
      higher up to day 15 in ulcers treated with 2% hydrogen peroxide cream than in
      those treated with placebo cream. Vascular perfusion was significantly higher in
      ulcers treated with 3.5% hydrogen peroxide cream than in ulcers treated with
      either 1.5% hydrogen peroxide cream or placebo. Adjacent control sites in guinea
      pigs whose ulcers were treated with hydrogen peroxide cream showed increased
      vascular perfusion compared with corresponding sites in animals whose ulcers were
      treated with placebo. Even distant flank control sites of ulcers treated with
      3.5% hydrogen peroxide cream showed increased vascular perfusion. CONCLUSION:
      Treatment of ischemia-induced ulcers with hydrogen peroxide cream enhanced
      cutaneous blood recruitment not only to ulcers and adjacent sites, but also to
      distant sites.

PMID- 7622649
TI  - Comparative epidemiologic study of premalignant and malignant epithelial
      cutaneous lesions developing after kidney and heart transplantation.
AB  - BACKGROUND: Cutaneous carcinomas are the most frequent cancers in organ
      transplant recipients. OBJECTIVE: Our purpose was to compare the epidemiologic
      data of cutaneous premalignant and malignant epithelial lesions in kidney and
      heart transplant recipients. METHODS: A total of 580 kidney and 150 heart
      transplant recipients were examined for the presence of premalignant and
      malignant epithelial lesions. RESULTS: A twofold increase in incidence of
      premalignant and malignant epithelial lesions was found in heart compared with
      kidney transplant recipients. Heart transplant recipients were older at
      transplantation, received more intense immunosuppressive treatment, and had a
      shorter delay from transplantation to the development of the first lesion. The
      squamous cell carcinoma/basal cell carcinoma ratio was 2.37:1 in kidney and
      1.08:1 in heart transplant recipients. The extracephalic location represented 60%
      of the premalignant and malignant epithelial lesions in kidney and 30% in heart
      transplant recipients. CONCLUSION: Cutaneous premalignant and malignant
      epithelial lesions in kidney and heart transplant recipients show epidemiologic
      differences that can tentatively be explained by the older age and the more
      intense immunosuppressive treatment of heart transplant recipients.

PMID- 7622650
TI  - Treatment of mycosis fungoides with photochemotherapy (PUVA): long-term follow
      up.
AB  - BACKGROUND: Mycosis fungoides (MF) is a non-Hodgkin's T-cell lymphoma of the skin
      that often begins as limited patches and plaques with slow progression to
      systemic involvement. No studies have been published comparing photochemotherapy
      (PUVA) with other topical therapies in the treatment of early-stage disease.
      OBJECTIVE: The purpose of the study was to examine our long-term experience using
      PUVA to treat early-stage MF and to compare its effectiveness and side-effect
      profile with other previously reported topical therapies. METHODS: Eighty-two
      patients with MF (83% stage IA or IB) were treated with PUVA. Clinical and
      histologic features were observed for a period from 2 months to 15 years (median,
      43 months). RESULTS: A response was noted in 78 patients (95%) with complete
      clinical and histologic clearing in 53 patients (65%) for all stages. The mean
      duration of total complete response to PUVA for all stages was 43 months (3.6
      years). The mean survival of our study group for all stages was 8.5 years. Signs
      of chronic actinic skin damage were found in 10% of patients, including three
      patients with basal cell carcinomas and three patients with squamous cell
      carcinomas. In a nonrandomized comparison with previously reported data for other
      topical therapies, the efficacy and side-effect profile of PUVA compared
      favorably. CONCLUSION: PUVA is an effective and safe therapy for MF with
      prolonged disease-free remissions being achieved. Patients with stage I and II MF
      respond best to PUVA. Palliative therapy with PUVA is useful in more advanced
      cases of MF.

PMID- 7622651
TI  - Acne keloidalis nuchae: treatment with excision and second-intention healing.
AB  - BACKGROUND: Acne keloidalis nuchae (AKN) is a chronic inflammatory disorder of
      the posterior aspect of the neck and occipital region of the scalp. Despite
      numerous medical and surgical treatment modalities, few offer cure or a superior
      cosmetic result for patients with extensive disease. OBJECTIVE: Our purpose was
      to determine whether excision with second-intention healing is an effective
      therapeutic modality for AKN. METHODS: Excision of the involved area to the level
      of the muscle fascia or deep subcutaneous tissue was performed in six patients.
      Postoperative sites healed by second intention. RESULTS: Four of six patients had
      a horizontal elliptic excision of the involved area that included the posterior
      hairline, with good to excellent results. The other two, who received nonelliptic
      excision of affected scalp that spared the hairline, had slower wound healing and
      poor contraction. CONCLUSION: Best results were achieved in excision of AKN with
      second-intention healing when the excision was a horizontal ellipse of the
      posterior aspect of the scalp including the posterior hairline.

PMID- 7622652
TI  - Inflammation in acne vulgaris.
AB  - Recent findings suggest that an overly vigorous immune response to
      Propionibacterium acnes may be the fundamental problem in patients with
      inflammatory acne. These data and evidence for the antiinflammatory effects of
      acne medications are reviewed.

PMID- 7622654
TI  - Clinical pearl: systemic antifungal drugs and drug interactions.

PMID- 7622653
TI  - Stanozolol as a novel therapeutic agent in dermatology.
AB  - Anabolic steroids are synthetic derivatives of testosterone that were developed
      in the 1950s in an attempt to dissociate the anabolic and androgenic effects of
      testosterone. The anabolic steroid stanozolol has been particularly helpful
      because it has one of the largest anabolic/androgenic ratios. In addition,
      stanozolol has substantial fibrinolytic properties. We discuss the safety profile
      and the use of stanozolol for a variety of clinical applications. Stanozolol is
      approved for use in the treatment of hereditary angioedema, but numerous reports
      have detailed the effectiveness of this agent in the treatment of urticaria,
      Raynaud's phenomenon, and, more recently, cryofibrinogenemia and
      lipodermatosclerosis. Side effects are mostly dose related and are preventable
      with appropriate follow-up.

PMID- 7622655
TI  - Guidelines of care for office surgical facilities. Part II. Self-assessment
      checklist. American Academy of Dermatology.

PMID- 7622657
TI  - Cutaneous viral infections.

PMID- 7622658
TI  - Indoor tanning: risks, benefits, and future trends.
AB  - The indoor tanning industry is a $1 billion-a-year business in the United States,
      and use of these high-intensity UVA tanning devices continues to grow. Many
      members of the medical community are concerned about the safety of these largely
      unregulated devices, but tanning salon operators state such concerns are
      unfounded and unproved. A comprehensive review of current knowledge of the
      operation and effects of indoor tanning is presented. The effects of UV radiation
      (especially UVA) on experimental animals and human beings are examined. Both
      acute and chronic effects are delineated from experimental sources as well as
      from epidemiologic studies and clinical observations. Existing safety regulations
      are described. Information on operator knowledge and compliance with existing
      safety regulations is reviewed.

PMID- 7622656
TI  - Guidelines of care for Mohs micrographic surgery. American Academy of
      Dermatology.

PMID- 7622660
TI  - Idiopathic lichen planus: treatment with metronidazole.

PMID- 7622659
TI  - Actinic lentigines versus skin cancer risk in albinos in northern Tanzania.

PMID- 7622661
TI  - Familial scleroderma-like deformity of the fingers.

PMID- 7622662
TI  - Panniculitis in juvenile dermatomyositis.

PMID- 7622663
TI  - Cell-mediated sensitization to jellyfish antigens confirmed by positive patch
      test to Olindias sambaquiensis preparations.

PMID- 7622664
TI  - Phaeohyphomycosis and Mycobacterium fortuitum abscesses in a patient receiving
      corticosteroids for sarcoidosis.

PMID- 7622665
TI  - Paraneoplastic pemphigus in the absence of a known neoplasm.

PMID- 7622666
TI  - Invasive Trichophyton rubrum infection in the immunocompromised host: report of
      three cases.

PMID- 7622667
TI  - "Nevocentric" erythema multiforme: not unique.

PMID- 7622668
TI  - Griseofulvin ineffective in balanitis circumscripta plasmacellularis.

PMID- 7622669
TI  - Prevalence of autoimmune diseases in the family members of patients with
      pemphigus vulgaris.

PMID- 7622670
TI  - Factors that exacerbate linear IgA disease.

PMID- 7622671
TI  - Dermographic pruritus: invisible dermographism.

PMID- 7622672
TI  - Separation of oviposition-stimulating peptides and myotropic factors from head
      extracts of Galleria mellonella L.: comparative effects of myotropic and non
      myotropic factors on egg laying.
AB  - Methanolic extracts from heads of the wax moth, Galleria mellonella L. contain
      several factors that stimulate oviposition of virgin females in vivo and
      spontaneous contractions of the oviduct in vitro of the cricket, Gryllus
      bimaculatus. The myotropic and egg-laying activities behaved distinctly during
      all steps of purification, including fractionation on reverse-phase high
      performance liquid chromatography. A novel neuropeptide was isolated from
      Galleria mellonella. The peptide does not increase the motility of isolated
      cricket oviducts. Among 13 other myotropic or non-myotropic factors studied, none
      were found to be as potent as the new peptide in stimulating egg-laying activity.
      The dose-response curves of myotropic and non-myotropic factors indicate that (i)
      proctolin, L-glutamate, octopamine, leucokinin-VI, leucopyrokinin, ecdysone and
      20-hydroxy-ecdysone, or equivalent structures, might be involved in Galleria
      mellonella oviposition control, and (ii) that only the novel wax moth
      neuropeptide has the ability to trigger egg laying in that insect. The
      significance of these findings is discussed.

PMID- 7622673
TI  - Adaptations of the reed frog Hyperolius viridiflavus (Amphibia, Anura,
      Hyperoliidae) to its arid environment. VII. The heat budget of Hyperolius
      viridiflavus nitidulus and the evolution of an optimized body shape.
AB  - Estivating reed frogs of the superspecies Hyperolius viridiflavus are
      extraordinarily resistant to the highly adverse climatic conditions prevailing in
      their African savanna habitats during dry season (air temperature up to 45
      degrees C, solar radiation load up to 1000 W.m-2, no water replenishment possible
      for up to 3 months). They are able to withstand such climatic stress at their
      exposed estivation sites on dry plants without evaporative cooling. We developed
      a heat budget model to understand the mechanisms of how an anuran can achieve
      this unique tolerance, and which allows us to predict the anuran's core and
      surface temperature for a given set of environmental parameters, to within 4% of
      the measured values. The model makes it possible to quantify some of the adaptive
      mechanisms for survival in semiarid habitats by comparing H. viridiflavus with
      anurans (H. tuberilinguis and Rana pipiens) of less stressful habitats. To
      minimize heat gain and maximize heat loss from the frog, the following points
      were important with regard to avoiding lethal heat stress during estivation: 1)
      solar heat load is reduced by an extraordinarily high skin reflectivity for solar
      radiation of up to 0.65 under laboratory and even higher in the field under dry
      season conditions. 2) The half-cylindrical body shape of H. viridiflavus seems to
      be optimized for estivation compared to the hemispheroidal shape usually found
      for anurans in moist habitats. A half-cylinder can be positioned relative to the
      sun so that large surface areas for conductive and convective heat loss are
      shielded by a small area exposed to direct solar radiation. 3) Another important
      contribution of body shape is a high body surface area to body mass ratio, as
      found in the estivating subadult H. viridiflavus (snout-vent lengths of 14-20 mm
      and body weights of 350-750 mg) compared to adult frogs (24-30 mm, 1000-2500 mg)
      which have never been observed to survive a dry season. 4) These mechanisms
      strongly couple core temperature to air temperature. The time constant of the
      core temperature is 29 +/- 10 s. Since air temperature can be 43-45 degrees C, H.
      viridiflavus must have a very unusual tolerance to transient core temperatures of
      43-45 degrees C. 5) If air temperature rises above this lethal limit, the
      estivating frog would die despite all its optimizations, but moving from an
      unsuited to a more favorable site during estivation can be extremely costly in
      terms of unavoidably high evaporative water loss. Therefore, H. viridiflavus must
      have developed behavioral strategies for reliably choosing estivation sites with
      air temperature staying on average within the vital range during the whole dry
      season.

PMID- 7622675
TI  - Pineal parenchymal tumors: CT and MR features.
AB  - OBJECTIVE: Our goal was to characterize the CT, MR, and pathologic features of
      pineal parenchymal tumors (PPTs). MATERIALS AND METHODS: We retrospectively
      reviewed 19 cases of resected PPTs with pathologic confirmation [10 pineocytomas
      (PCs), 1 mixed pineocytoma-pineoblastoma (PC-PB), and 8 pineoblastomas (PBs)],
      noting clinical, CT, and MRI features. RESULTS: Six male and four female patients
      presented with PC, one female patient with mixed PC-PB, and seven female and one
      male patient with PB. The CT imaging revealed 6 of 10 round and 6 of 10 small- to
      medium-sized masses; 7 of 9 were homogeneous, 1 of which appeared cystic. The
      mixed PC-PB was round and homogeneous. Eight precontrast CT scans of PCs and the
      PC-PB demonstrated calcifications, either peripheral (four of eight) or central
      (four of eight, including the mixed tumor). Pineocytomas were hypodense (five of
      seven) tumors, with heterogeneous postcontrast enhancement (five of seven). Most
      PBs (six of eight) were lobulated, and five of eight were homogeneous. Four of
      eight PBs imaged with CT were noncalcified hyperdense masses, which enhanced
      homogeneously. Pineocytomas and the PC-PB had variable signal intensity on MRI.
      Most PBs were hypo- to isointense on T1-weighted images, and six of six enhanced
      heterogeneously postgadolinium. CONCLUSION: Pineocytomas are predominantly
      smaller, round, hypodense, homogeneous masses with calcifications, particularly
      peripheral. They enhance heterogeneously on CT and present with a lesser degree
      of hydrocephalus in older patients. Pineoblastomas, on the other hand, are
      larger, lobulated, homogeneous tumors, are infrequently calcified, and present
      with a greater degree of hydrocephalus, often in young females. They tend to be
      hyperdense on CT and hypo- to isointense on T1-weighted images and enhance
      homogeneously on CT and heterogeneously on MRI.

PMID- 7622674
TI  - Bacterial lipopolysaccharide (LPS) and interleukin 1 (IL-1) exert multiple
      physiological effects in the tilapia Oreochromis mossambicus (Teleostei).
AB  - To gain insight in immuno-endocrine communication in teleosts the physiological
      effects of interleukin 1 and bacterial lipopolysaccharide in teleosts were
      investigated. Tilapia (Oreochromis mossambicus) were treated with murine
      interleukin 1 and E. coli lipopolysaccharide in vivo, and lipopolysaccharide was
      administered to pituitary lobes and head kidneys in vitro. The integument of the
      fish appeared to be a sensitive target for the preparations tested, since
      proliferation of chloride cells and of epidermal mucous cells was observed as
      well as an increase in epidermal thickness. These effects may relate to an acute
      phase-like reaction caused by the treatments. Lipopolysaccharide administration
      furthermore resulted in an increase in plasma free fatty acids levels.
      Lipopolysaccharide, but not interleukin 1, stimulated the interrenal axis of the
      fish, as judged by the increase in cortisol production measured in superfusion of
      head kidneys. In addition to these in vivo effects, lipopolysaccharide also
      displayed several effects in vitro. Pituitary adrenocorticotropic hormone, as
      well as alpha-melanocyte stimulating hormone, release was inhibited, and the head
      kidney responsiveness to adrenocorticotropic hormone was inhibited after
      pretreatment of the tissue with the E. coli product. This latter effect coincided
      with the release of an unidentified alpha-melanocyte stimulating hormone
      immunoreactive fraction by the head kidneys which could be stimulated by
      lipopolysaccharide. The data strongly support the notion that the immune system
      is involved in adaptive regulations in teleosts, and that immunoendocrine
      interactions are phylogenetically old mechanisms.

PMID- 7622676
TI  - Supratentorial ependymomas and subependymomas: CT and MR appearance.
AB  - OBJECTIVE: Our goal was to characterize the CT and MR features of supratentorial
      ependymomas and subependymomas. MATERIALS AND METHODS: The CT or MRI examinations
      of 11 supratentorial ependymomas (average patient age: 16 years) and 3
      supratentorial subependymomas (average age: 60 years) were analyzed for tumor
      size, location, and appearance. RESULTS: Ependymomas were periventricular (nine),
      intraventricular (one), or both (one) and averaged 4 cm in diameter. Four of nine
      ependymomas examined by CT were calcified. Eight ependymomas had a cystic
      component. All seven ependymomas evaluated with MRI demonstrated prolonged T1 and
      T2 relaxation, with two having foci thought to represent intratumoral hemorrhage.
      The MR contrast enhancement patterns included an enhancing nodule within the wall
      of a cyst (four), heterogeneous enhancement of cystic/solid lesions (two), and
      homogeneous enhancement of a solid lesion (one). All subependymomas were solid
      intraventricular masses, averaging 2.6 cm in diameter. One had small amounts of
      calcification, and none were cystic. All three were isointense or hypointense to
      white matter on T1-weighted MR images and heterogeneous or hyperintense on T2
      weighted images, with variable enhancement characteristics. Early (< 1 year)
      postsurgical recurrence was seen in two ependymomas and one subependymoma.
      CONCLUSION: Supratentorial ependymomas are typically large, cystic, calcified,
      extraventricular masses found in children and young adults. Supratentorial
      subependymomas are generally solid, intraventricular masses that are usually
      smaller than ependymomas and occur in an order patient population.

PMID- 7622677
TI  - Subcortical hemorrhage: marker for radiographically occult cerebral vein
      thrombosis on CT.
AB  - OBJECTIVE: Cerebral vein thrombosis (CVT) is a potentially life-threatening
      entity with a protean clinical presentation that can lead to delays in diagnosis
      and treatment. Computed tomography of the brain is often the initial imaging tool
      in evaluation of these patients, but is frequently nondiagnostic. This study
      identifies subcortical hemorrhage (SCH) as an indicator of radiographically
      occult CVT on CT. MATERIALS AND METHODS: A retrospective analysis of all subjects
      (n = 24) with CVT proven by MRI over a 4 year period was performed. The CT
      examinations of all subjects were evaluated for the presence of SCH and signs of
      CVT. An evaluation of the correlation between findings on CT and MRI as well as
      the delay in diagnosis and treatment secondary to unrecognized CVT on CT was also
      performed. RESULTS: Subcortical hemorrhage was noted in 9 of 24 (38%) subjects
      with CVT by MRI. The CT antedated MRI in eight of these subjects as the initial
      evaluation for presenting neurological symptoms. Subcortical hemorrhage was noted
      in six of eight of these subjects as the sole CT finding. Subcortical hemorrhage
      as well as CVT was seen in one subject, and no abnormality was seen in the final
      subject. Cerebral vein thrombosis was not suggested as a diagnosis in any of the
      six subjects with SCH as the sole radiographic finding. In all six of these
      cases, a delay in diagnosis occurred pending MRI obtained subsequently secondary
      to clinical deterioration. CONCLUSION: Subcortical hemorrhage can be seen in
      association with acute CVT and can be the sole abnormality on head CT. SCH as an
      isolated finding on CT suggests the possibility of unrecognized CVT, warranting
      further investigation by MRI.

PMID- 7622679
TI  - Hemiballismus: CT and MR findings.
AB  - OBJECTIVE: Our aim was to determine the frequency with which a lesion responsible
      for hemiballismus was detectable on CT and MR examinations. MATERIALS AND
      METHODS: The CT and MR examinations of six patients with hemiballismus were
      reviewed. Three patients underwent MRI alone, two CT alone, and one underwent
      both CT and MRI. Sites considered as possible locations for a lesion causing
      hemiballismus included the subthalamic nucleus on the side contralateral to the
      movements, contralateral putamen, caudate nucleus, thalamus, corpus striatum,
      lenticular nucleus, substantia nigra, and the premotor and motor cortex. RESULTS:
      A lesion likely to account for hemiballismus was found in five patients
      (contralateral subthalamic nucleus in four patients, contralateral putamen in one
      patient). Causes of hemiballismus included infarction (one patient), hemorrhage
      (two patients), trauma (one patient), and an abscess (one patient). A responsible
      lesion was detected in all five patients who underwent MRI. In one patient who
      underwent CT alone, a responsible lesion was not identified. CONCLUSION: A lesion
      responsible for hemiballistic movements can generally be found on cross-sectional
      imaging examinations. Because the multiplanar imaging capability of MR appears to
      allow for sensitive detection of even small lesions in sites likely to cause
      hemiballismus, MRI offers the best means of imaging these patients.

PMID- 7622678
TI  - Differential diagnosis of CNS lesions in AIDS patients by FDG-PET.
AB  - OBJECTIVE: The aim of this study was to evaluate the potential of FDG-PET in the
      differential diagnosis of CNS lesions in patients with AIDS, particularly to
      differentiate between toxoplasmosis and lymphoma. MATERIALS AND METHODS: We
      examined 11 AIDS patients, 6 with toxoplasmosis, 1 with a tuberculoma, and 4 with
      a primary CNS lymphoma. The FDG uptake within the lesion was compared with the
      uptake in a contralateral brain area [standardized uptake value (SUV)]. RESULTS:
      In all subjects with cerebral infections (toxoplasmosis, tuberculoma), the SUV
      ratio was significantly (p < 0.05) lower than the SUV ratio in patients with
      lymphoma (range of 0.3-0.7 vs. 1.7-3.1) with no overlap of the uptake values.
      CONCLUSION: In conclusion, FDG-PET may help to characterize these lesions
      metabolically and play an important role in the clinical management of AIDS
      patients with CNS involvement.

PMID- 7622680
TI  - Preserved pontine glucose metabolism in Alzheimer disease: a reference region for
      functional brain image (PET) analysis.
AB  - OBJECTIVE: Our goal was to examine regional preservation of energy metabolism in
      Alzheimer disease (AD) and to evaluate effects of PET data normalization to
      reference regions. MATERIALS AND METHODS: Regional metabolic rates in the pons,
      thalamus, putamen, sensorimotor cortex, visual cortex, and cerebellum (reference
      regions) were determined stereotaxically and examined in 37 patients with
      probable AD and 22 normal controls based on quantitative 18FDG-PET measurements.
      Following normalization of metabolic rates of the parietotemporal association
      cortex and whole brain to each reference region, distinctions of the two groups
      were assessed. RESULTS: The pons showed the best preservation of glucose
      metabolism in AD. Other reference regions showed relatively preserved metabolism
      compared with the parietotemporal association cortex and whole brain, but had
      significant metabolic reduction. Data normalization to the pons not only enhanced
      statistical significance of metabolic reduction in the parietotemporal
      association cortex, but also preserved the presence of global cerebral metabolic
      reduction indicated in analysis of the quantitative data. CONCLUSION: Energy
      metabolism in the pons in probable AD is well preserved. The pons is a reliable
      reference for data normalization and will enhance diagnostic accuracy and
      efficiency of quantitative and nonquantitative functional brain imaging.

PMID- 7622681
TI  - Orbital cavernous hemangioma: findings on sequential Gd-enhanced MRI.
AB  - OBJECTIVE: To describe the contrast enhancement pattern of orbital cavernous
      hemangioma on sequential Gd-enhanced MRI. MATERIALS AND METHODS: Six patients
      with an orbital mass lesion were examined with T1- and T2-weighted spin echo MRI.
      After intravenous administration of Gd-chelate at a dose of 0.1 mmol/kg, T1
      weighted spin echo sequences were performed immediately after, after 15 to 30
      min, and up to 1 h after the injection. In two patients a fat saturation prepulse
      was given before the Gd-enhanced study. RESULTS: In all patients the lesions were
      isointense to muscle on the T1-weighted sequence and hyperintense to muscle on
      the T2-weighted sequences. After gadolinium, all lesions showed initial central
      patchy enhancement. Between 20 and 60 min after the injection the lesions showed
      total and homogeneous filling up. CONCLUSIONS: Progressive and total homogeneous
      filling up of an orbital mass of Gd-enhanced MRI is a pathognomonic sign of
      cavernous hemangioma.

PMID- 7622682
TI  - MR signal changes in bone marrow of mandible in hematologic disorders.
AB  - OBJECTIVE: Signal intensity changes in bone marrow of the mandible were observed
      in cases with hematologic disorders. MATERIALS AND METHODS: Using MRI, bone
      marrow intensity of the mandible was observed in six patients with polycythemia
      vera, acute leukemia, myelofibrosis, and malignant lymphoma. A control group was
      also evaluated for comparison. RESULTS: The bone marrow of the condyloid process
      of the mandible converts to yellow marrow in early childhood. Therefore, T1
      weighted imaging showed the marrow of the mandible to have a high signal
      intensity similar to that of fat in the control cases. In contrast, the bone
      marrow of the mandible in the patients exhibited lower intensity than that of fat
      and was enhanced after Gd-DTPA injection. CONCLUSION: In hematologic diseases MRI
      detected the signal changes of the mandible. More attention should be focused on
      the marrow intensity of the mandible in the routine cranial MR examinations in
      patients with hematologic disorders.

PMID- 7622683
TI  - Neck pain and dysphagia: MRI of retropharyngitis.
AB  - OBJECTIVE: Acute neck pain developing over hours or a few days is often an
      alarming symptom that may be due to an inflammatory process or another process
      affecting the spine or the spinal canal, nerve roots, or peripheral nerves.
      MATERIALS AND METHODS: Four patients with acute onset of neck pain and dysphagia
      are presented. They were examined with MRI and CT, barium swallow, and plain
      radiography of the neck. RESULTS: In all patients T2-weighted MRI demonstrated a
      slitlike area with high signal intensity in the retropharyngeal space at the
      level C2-C7 suggestive of inflammation in the retropharyngeal space. The patients
      were treated with antibiotics and antiinflammatory drugs and became asymptomatic
      rapidly. CONCLUSION: We suggest the name retropharyngitis for this characteristic
      disease entity. Patients with acute onset of neck pain and dysphagia should
      undergo MRI to reach the correct diagnosis rapidly.

PMID- 7622684
TI  - Primary adenoid cystic carcinoma of the cervical trachea mimicking thyroid tumor:
      CT evaluation.
AB  - OBJECTIVE: Our goal was to describe the CT characteristics of adenoid cystic
      carcinomas of the trachea mimicking thyroid tumors. MATERIALS AND METHODS:
      Computed tomography of four patients with pathologically proved adenoid cystic
      carcinomas extending into the thyroid gland was retrospectively reviewed. One
      case was also examined with MR. RESULTS: The masses encircling the trachea and
      circumferential thickening of the tracheal wall were demonstrated in all four
      cases. The longitudinal extent of the tracheal wall thickening was also
      demonstrated in all cases. The tumors had a broad base on the trachea and convex
      margin on the thyroid gland. They were all homogeneous, generally smoothly
      marginated, and isoattenuating on postcontrast CT scans. CONCLUSION: Adenoid
      cystic carcinomas were usually seen on CT scans as homogeneous masses encircling
      the posterolateral trachea with thickening of the tracheal wall in the transverse
      and longitudinal planes. These CT characteristics may be helpful in the
      differential diagnosis of adenoid cystic carcinomas mimicking thyroid tumors.

PMID- 7622685
TI  - Spiral CT and 3D image reconstruction of vascular rings and associated
      tracheobronchial anomalies.
AB  - OBJECTIVE: Spiral CT (SCT) angiography and three-dimensional (3D) reconstruction
      methods represent noninvasive tools in diagnosis of vascular rings and associated
      tracheobronchial anomalies in the pediatric age group. MATERIALS AND METHODS:
      Three patients suspected on clinical and conventional radiological grounds of
      having vascular and tracheobronchial anomalies were examined using SCT. Three
      dimensional images were reconstructed using a surface rendering technique.
      RESULTS: In one case the diagnosis of complete double aortic arch was confirmed
      by angiography. In the other two patients the SCT and 3D reconstruction
      established the diagnosis of pulmonary sling and right aortic arch associated
      with left aberrant subclavian artery and angiography could be avoided.
      CONCLUSION: Spiral CT and color-coded 3D reconstruction represent important
      additional tools and perhaps alternatives to angiography or other noninvasive
      techniques used in evaluation of vascular anomalies of the thoracic aorta and
      pulmonary arteries in infants and children.

PMID- 7622686
TI  - Aortic motion: a potential pitfall in CT imaging of dissection in the ascending
      aorta.
AB  - OBJECTIVE: Artefacts complicate the diagnosis of thoracic aortic dissection by
      CT. Aortic compliance and cardiac motion may be responsible but the precise cause
      of these artefacts remains unclear. MATERIALS AND METHODS: Fifty consecutive
      clinical thoracic CT examinations performed on a Siemens Somatom Plus scanner (8
      mm slice thickness, 1 s scan time) were reviewed (mean patient age 56 years). For
      each examination, the presence, position, and displacement of motion artefact
      from the aortic wall were noted at three ascending aortic levels. Cine ultrafast
      CT on 10 volunteers (mean age 49 years) was used to assess aortic motion for the
      same three levels (8 mm slice thickness, 50 ms scan time). Digital subtraction of
      consecutive cine CT allowed the position of the aortic wall throughout the
      cardiac cycle to be tracked. RESULTS: Curvilinear motion artefacts were seen in
      the ascending aorta in 17 conventional CT scans, occurring left anterior and
      right posterior in all but one and maximally at the aortic root (mean amplitude
      3.5 mm). Ultrafast CT, however, showed no motion artefact and no significant
      change in aortic area with systole. Aortic motion in the sagittal-oblique plane
      at the ascending aorta was confirmed. CONCLUSION: Motion artefacts simulating
      ascending aortic dissection occur frequently on conventional CT. Their position
      is predictable and is related to systolic aortic motion from the left anterior to
      the right posterior position.

PMID- 7622687
TI  - Abdominal manifestations of sarcoidosis in CT studies.
AB  - OBJECTIVE: The purpose of this study is to demonstrate the spectrum of abdominal
      CT findings in patients with tissue proved sarcoidosis, estimate their
      prevalence, and correlate abdominal findings with stage of thoracic disease.
      MATERIALS AND METHODS: Between 1987 and 1993, 140 patients with tissue proved
      sarcoidosis underwent abdominal or chest CT at our institution. After exclusions,
      49 patients remained. Abdominal CT was retrospectively reviewed and the findings
      arrived at by consensus. Chest radiography within 1 month of CT was available for
      46 patients. Chest radiography was retrospectively reviewed and stage of thoracic
      disease arrived at by consensus. RESULTS: Splenic abnormalities consisted of
      splenomegaly, low density lesions, and punctate calcifications. Hepatic
      sarcoidosis manifested as hypovascular lesions, hepatomegaly, and punctate
      calcifications. Lymphatic abnormalities consisted of lymphadenopathy, most
      commonly between 1 and 2 cm, and an increased number of normal sized lymph nodes.
      CONCLUSION: Sarcoidosis produces splenic abnormalities in 53% of patients, liver
      abnormalities in 16%, and lymphatic findings in 43%. No correlation was
      demonstrated between the abdominal findings and stage of thoracic sarcoidosis.

PMID- 7622689
TI  - Endoscopic MRI using 3D-spoiled GRASS (SPGR) sequence for local staging of rectal
      carcinoma.
AB  - OBJECTIVE: Magnetic resonance imaging was performed with an MR endoscope to
      evaluate the depth of invasion of rectal carcinomas. MATERIALS AND METHODS:
      Twenty-two patients with rectal carcinomas were studied prior to surgery with MRI
      using a 3D-fast spoiled GRASS (SPGR) sequence, a nonmagnetic endoscope and an
      antenna probe. RESULTS: The MR images on 3D-fast SPGR sequence showed that the
      normal bowel mucosa had a high signal intensity, the submucosal layer had a low
      signal intensity, and the muscularis propria had moderate signal intensity. Small
      tumors had moderate signal intensity similar to the muscularis propria. Advanced
      tumors with considerable volume revealed heterogeneous findings with intermediate
      and low signal intensities. The depth of wall invasion by rectal carcinoma was
      correctly staged with endoscopic MRI in 16 of 22 patients. CONCLUSION: This
      technique may be useful for the accurate staging of the depth of invasion by
      rectal carcinomas.

PMID- 7622688
TI  - Liver transplantation: significance of the periportal collar on MRI.
AB  - OBJECTIVE: Liver transplantation is performed with increasing success and
      frequency all over the world. Experience with MRI of the liver allograft is,
      however, limited. This study was designed to correlate MRI to clinical-laboratory
      findings, CT, and biopsy and to evaluate the significance of the periportal
      collar on MRI. MATERIALS AND METHODS: Fourteen patients who had undergone
      orthotopic liver transplantation were studied by CT and MRI [T1-weighted imaging:
      gradient-echo, repetition time/echo time (TR/TE) 306/14 ms, theta 90 degrees;
      proton density and T2-weighted imaging: spin-echo, TR/TE 1,600/30-120 ms]. Three
      patients also had follow-up MR examinations 43 days, 89 days, and 5 months after
      transplantation. RESULTS: Magnetic resonance imaging demonstrated a perivascular
      collar around central portal venous branches in all 14 patients and around
      peripheral portal branches in 10 of the 14 patients on the initial MRI study. The
      perivascular collar showed low signal intensity on T1-weighted imaging and an
      increase in signal intensity on T2-weighted multiecho imaging. The distribution
      and prevalence of central and peripheral periportal collars were identical on MR
      and CT. Peripheral periportal collars were seen in 9 patients who had no clinical
      laboratory signs of rejection. In 3 patients with biopsy-proved rejection, the
      periportal collar was less prominent on MR at the time of rejection when compared
      with MR performed when the patient had no signs of transplant rejection.
      CONCLUSION: A perivascular collar in a patient with liver transplantation is
      likely to be related to impaired lymph drainage after surgical interruption of
      the draining lymph vessels and lymphedema. In contrast to previous CT reports,
      however, a perivascular collar around peripheral portal branches does not appear
      to correlate to rejection, since it is frequently observed in the normal liver
      allograft.

PMID- 7622690
TI  - Chemotherapy-induced changes in uterine volume: CT study.
AB  - OBJECTIVE: The goal of this study was to quantify changes in uterine volume
      during and after chemotherapy for breast cancer. MATERIALS AND METHODS: Fifty
      eight patients (mean age 42 years) with advanced breast cancer undergoing
      treatment with FLAC (5-fluorouracil, leucovorin, Adriamycin, and
      cyclophosphamide) were studied with serial pelvic CT. The transverse,
      anteroposterior, and sagittal measurements of the uterus were taken in each of
      the CT scans. The uterine volumes were calculated, normalized to baseline
      volumes, and graphically displayed for each patient. The temporal changes in
      uterine volume were correlated to the dates of chemotherapy administration and
      menstrual status. RESULTS: There was a striking and consistent loss of uterine
      volume with chemotherapy. This phenomenon was observed in 55 (95%) of the 58
      patients. The mean minimum uterine volume was 58.3 +/- 20.2% compared with the
      baseline. This loss of uterine volume began after the administration of the first
      cycle of chemotherapy and progressed during subsequent cycles. It coincided with
      loss of normal menses in all patients. After completion of chemotherapy, there
      was a recovery of the uterine volume in 12 of the 16 patients who had follow-up
      CT. The mean recovery uterine volume was 108.4 +/- 49.8% of baseline. Menses
      recovered in four of these. CONCLUSION: Chemotherapy causes loss of uterine
      volume, which usually recovers after the withdrawal of chemotherapy in
      premenopausal women. This change should not be mistaken for a therapeutic
      response of primary or secondary malignancy within the uterus or be confused with
      subsequent uterine changes due to tamoxifen.

PMID- 7622691
TI  - Denervation hypertrophy of muscle: MR features.
AB  - OBJECTIVE: Denervation hypertrophy is an entity well recognized in the neurology
      literature, but with little mention in the radiology literature. Denervation
      hypertrophy occurs when a muscle paradoxically enlarges rather than atrophies in
      response to loss of innervation. The purpose of this report is to describe the MR
      appearance of true hypertrophy and pseudohypertrophy of muscle following
      denervation. MATERIALS AND METHODS: The clinical data and MRI findings in three
      patients with muscle enlargement due to denervation hypertrophy are reviewed
      retrospectively. Two women and one man aged 19-80 years were included.
      Denervation resulted from spinal stenosis in one patient, a herniated thoracic
      disc in another, and spina bifida with a tethered cord in the third. RESULTS:
      True hypertrophy of a single muscle was seen in one patient and pseudohypertrophy
      of two muscles was present in one patient. One patient had one muscle with true
      hypertrophy and one muscle with pseudohypertrophy. Electromyographic examination
      was performed and was consistent with denervation in two patients. Biopsy
      confirmation of denervation was obtained in two patients. All five abnormal
      muscles exhibited increased volume, well defined margins, and normal contour. In
      true hypertrophy the enlarged muscle was isointense with normal muscle on all MRI
      sequences. In pseudohypertrophy the MRI appearance was consistent with an
      excessive amount of fat interspersed throughout normal muscle. CONCLUSION:
      Magnetic resonance in these cases established muscle hypertrophy rather than
      neoplasm as the cause of a palpable mass. If muscle hypertrophy or
      pseudohypertrophy is seen on an MR examination of an enlarged extremity, the
      possibility of an underlying neurologic process should be considered.

PMID- 7622692
TI  - MRI of elastofibroma dorsi.
AB  - OBJECTIVE: To determine if the MR features of elastofibroma are sufficient for
      diagnosis of this neoplasm. MATERIALS AND METHODS: The MR studies of two patients
      with pathologically proven bilateral elastofibromas were reviewed
      retrospectively. RESULTS: In each patient, bilateral semilunar soft-tissue masses
      demonstrating signal intensities isointense to that of muscle were identified in
      the periscapular regions deep to the posterolateral musculature of the chest.
      Focal linear areas of fat were present. The biopsy specimens of both patients
      demonstrated a positive reaction to the elastin stains. CONCLUSION: A
      periscapular soft-tissue neoplasm demonstrating a pattern of linear alternating
      regions of high and intermediate signal intensity on T1- and T2-weighted spin
      echo MRI should be sufficient to allow the diagnosis of elastofibroma.

PMID- 7622693
TI  - MR evaluation of the anterior cruciate ligament: value of axial images.
AB  - OBJECTIVE: To investigate the accuracy of diagnosing anterior cruciate ligament
      (ACL) tears with axial MR imaging. MATERIALS AND METHODS: Two blinded independent
      observers retrospectively reviewed axial T2 weighted or FSE fat suppressed
      imaging of the knee from 47 patients. Arthroscopy had demonstrated a complete
      tear of the ACL in 25 patients and a normal ACL in 22 patients. The two criteria
      used to diagnose ACL tears on sequential axial imaging were (a) lack of
      visualization of the ACL in its expected course or (b) focal increased signal in
      the expected course of the ACL. RESULTS: Observer 1 demonstrated a sensitivity of
      92% (23 of 25) and a specificity of 100% (22 of 22) in diagnosing ACL tears (chi
      2 = 39.6, p < 0.001). Observer 2 demonstrated a sensitivity of 92% (23 of 25) and
      a specificity of 82% (18 of 22) in diagnosing ACL tears (chi 2 = 26.1, p <
      0.001). The Kappa value was 0.75 (agreement in 41 of 47 cases), indicating a high
      degree of intraobserver agreement. CONCLUSION: Axial T2 weighted or FSE fat
      suppressed imaging provides an accurate means of confirming the diagnosis of ACL
      tears.

PMID- 7622694
TI  - Discoid menisci in children: MR features.
AB  - OBJECTIVE: To define the MR appearance of discoid meniscus in children. MATERIALS
      AND METHODS: In 22 children (15 girls and 7 boys; age range 5-17 years; median
      age 9 years) who were referred for evaluation of painful knees 27 discoid lateral
      menisci were identified. Meniscal shape and signal intensity and abnormalities of
      the surrounding structures were evaluated and compared with adult standards.
      Clinical (11 knees) or surgical (10 knees) follow-up was available on 16 patients
      (21 knees). RESULTS: The menisci were classified as slab type (no. 20) or wedge
      type (no. 7). Transverse diameter at the midbody was 22.4 mm (range 10.5-36.7 mm)
      for discoid lateral menisci and 6 mm (range 5.1-28.3 mm) for medial menisci. Of
      27 menisci, 23 had a central band of diffusely increased signal. Extension of
      intrameniscal signal to the joint space was noted in 16 of 23 menisci. Of 9
      patients with intrameniscal signal who underwent surgery, only 7 had tears.
      Associated popliteal cysts occurred in 3 knees. No medial meniscal injury was
      observed. CONCLUSION: The characteristic MRI appearance of symptomatic discoid
      meniscus in children is that of a diffusely thick meniscus with a slab
      configuration and diffusely increased intrameniscal signal that may or may not
      extend to the joint surface.

PMID- 7622695
TI  - Soft tissue coccidioidomycosis on MRI.
AB  - OBJECTIVE: To determine the appearance of soft tissue coccidioidomycosis on MRI.
      MATERIALS AND METHODS: Two cases of soft coccidioidomycosis with preoperative MR
      imaging are presented. RESULTS: Prospectively, infection was considered unlikely
      both clinically and on imaging studies. In retrospect, the MR appearance was
      nonspecific in one case and suggestive of infection in the other. CONCLUSION:
      Radiologists should be prepared to entertain coccidioidal abscess as a
      differential consideration when soft tissue masses are seen on MRI, even when
      infection is not suggested clinically.

PMID- 7622696
TI  - A fully automatic multimodality image registration algorithm.
AB  - OBJECTIVE: A fully automatic multimodality image registration algorithm is
      presented. The method is primarily designed for 3D registration of MR and PET
      images of the brain. However, it has also been successfully applied to CT-PET, MR
      CT, and MR-SPECT registrations. MATERIALS AND METHODS: The head contour is
      detected on the MR image using a gradient threshold method. The head region in
      the MR image is then segmented into a set of connected components using the K
      means clustering algorithm. When the two image sets are registered, the
      segmentation of the MR image indirectly generates a segmentation of the PET
      image. The best registration is taken to be the one that optimizes the
      segmentation induced on the PET image. In this article, the K-means minimum
      variance criterion is used as a cost function, and the optimization is performed
      using the method of coordinate descent. RESULTS: The algorithm was tested on 80
      H2 15O PET and MR image pairs from 10 subjects. Qualitatively correct results
      were obtained in all cases. With use of external markers visible in both image
      modalities, the average registration error was estimated to be < 3 mm.
      CONCLUSION: The algorithm presented in this article requires no user interaction
      and can be applied to a wide range of registration problems. Quantitative and
      qualitative evaluations of the algorithm indicate a high degree of accuracy.

PMID- 7622697
TI  - Herpes zoster vasculitis: demonstration by MR angiography.
AB  - A patient presented with multiple cerebral infarcts in various vascular
      territories after having been treated for herpes zoster ophthalmicus. Magnetic
      resonance angiography demonstrated multiple focal stenoses involving the proximal
      intracranial vessels which corresponded to endarteritis at autopsy.

PMID- 7622698
TI  - Foreign body giant cell reaction associated with epidermoid tumor: CT and MR
      findings.
AB  - A patient with a known epidermoid tumor presented with a new large ring-enhancing
      mass adjacent to the cyst. Histopathology showed foreign body giant cell reaction
      adjacent to the epidermoid cyst. The CT and MR imaging appearances are described.
      The neuroimaging findings are identical to malignant degeneration to squamous
      cell carcinoma.

PMID- 7622699
TI  - Serial cerebral MRI with FLAIR sequences in acute carbon monoxide poisoning.
AB  - In a patient with acute carbon monoxide (CO) poisoning in whom no delayed
      sequelae have been observed, MRI was performed serially from the time of
      exposure. When few clear findings were noted on conventional T2-weighted spin
      echo (SE) imaging, distinct hyperintense areas in the deep cerebral white matter
      were already evident on fluid attenuated inversion recovery (FLAIR) pulse
      imaging. These abnormal findings appeared to reflect a disease process differing
      from the acute phase disturbance of consciousness, namely the course of a
      gradually progressive demyelination. Neither serial intelligence tests nor single
      photon emission CT (SPECT) studies of regional cerebral blood flow conducted in
      the same period revealed any abnormalities. These results suggest that, in the
      subclinical phase in which there are few significant findings on T2-weighted SE
      imaging or SPECT, insidious demyelinating changes are already apparent on FLAIR
      imaging and that FLAIR imaging may thus be useful in the early diagnosis of the
      interval form of CO poisoning.

PMID- 7622700
TI  - MRI of the brain in Wilson disease: T2 signal loss under therapy.
AB  - Repeat examinations in a de novo patient with Wilson disease revealed an
      expansion of decreased signal intensities in the basal ganglia on T2-weighted
      imaging after initiation of copper trapping therapy. Since marked clinical
      improvement was associated with continued urinary copper excretion, iron
      depositioning in exchange for copper might explain these findings.

PMID- 7622701
TI  - Leptomeningeal and calvarial sarcoidosis: CT and MR appearance.
AB  - We report an unusual case of biopsy-proven combined leptomeningeal and calvarial
      sarcoidosis, as seen on CT and MRI. A solitary large thick plaque was present in
      the left hemisphere, with overlying bony infiltration and erosion and associated
      abundant vasogenic edema in the brain. The lytic lesion was visible on Scout
      digital radiography for CT slice positioning. The typical manifestations of CNS
      sarcoidosis, i.e., chronic leptomeningitis in the basilar cisterns and
      hypothalamic regions, were absent.

PMID- 7622702
TI  - Meningeal sarcoma mimicking an acute subdural hematoma on CT.
AB  - A case of meningeal sarcoma arising at the site of a prior subdural hematoma and
      mimicking an acute subdural hematoma on noncontrast CT is presented. The
      potential confusion between a hyperdense, nonhemorrhagic lesion and a hematoma on
      CT is highlighted. This report also reviews the possible relationship between
      meningeal injury and subsequent neoplastic change.

PMID- 7622703
TI  - Intramedullary gliofibroma: MR, ultrasound, and pathologic correlation.
AB  - We describe the clinical, MR, ultrasound, and pathologic findings of an
      intramedullary gliofibroma. This uncommon primitive tumor is thought to be of
      mixed glial and mesenchymal origin. Although the majority of tumors described to
      date have been histologically benign, clinical course has been quite variable. On
      MRI, the tumor we report was isointense to adjacent spinal cord on T1-weighted
      imaging and became hyperintense on proton and T2-weighted imaging. Enhancement
      with gadolinium diethylenetriamine pentaacetic acid was mild and slightly
      heterogeneous. Intraoperative ultrasound demonstrated widening of the lower
      thoracic cord. Echo pattern was generally similar to that of adjacent cord. The
      major differential diagnostic considerations include astrocytoma and ependymoma.

PMID- 7622704
TI  - Unusual long-standing Gd-DTPA enhancement in a chronic progressive myelopathy.
AB  - Chronic spinal syndromes without evidence of cord compression often represent a
      real diagnostic challenge. We report a case of chronic progressive myelopathy
      with an unusual long-standing gadolinium-diethylenetriamine pentaacetic acid
      (Magnevist, Berlex Laboratories) enhanced spinal cord lesion demonstrated on MRI,
      through a 14 month follow-up period. In the context of continuous neurological
      decline the patient underwent two biopsies at 1 year intervals. The final
      diagnosis was obtained only after the second biopsy, which demonstrated a
      demyelinating plaque with reactive astrocytosis. The clinical condition of our
      patient has been stable for 5 years. A repeated workup including MRI of the
      cervical and thoracic spine demonstrated a mildly atrophic cord in the upper
      thoracic region, with no evidence of pathological signal or enhancement at this
      time. Brain MRI and visual evoked potentials were normal. This case provides
      interesting clinical, pathological, and MRI correlations in a longitudinal follow
      up of a spinal demyelinating lesion.

PMID- 7622705
TI  - Ruptured sinus of Valsalva aneurysm: cine phase-contrast MR characterization.
AB  - Congenital sinus of Valsalva aneurysms are rare anomalies that usually go
      undetected unless they rupture. We report a case of a ruptured congenital sinus
      of Valsalva aneurysm, detected with cine phase-contrast MRI.

PMID- 7622707
TI  - Cortical and subcortical tubers in tuberous sclerosis and FLAIR sequence.

PMID- 7622706
TI  - CT of dystrophic calcification in subcutaneous soft tissues secondary to chronic
      insulin injection.
AB  - We describe a case of massive dystrophic subcutaneous calcification in the
      anterior thighs of a long-term insulin-dependent diabetic.

PMID- 7622708
TI  - Spinal calcifying granuloma on MRI.

PMID- 7622709
TI  - 3D angiography with helical CT in midgut volvulus.

PMID- 7622710
TI  - MR enhancement of hepatoma by superparamagnetic iron oxide (SPIO) particles.

PMID- 7622711
TI  - Persistent hypoglossal artery: MRI and MRA findings.

PMID- 7622712
TI  - Persistent sciatic artery: three-dimensional reconstructed CT (3D CT) image.

PMID- 7622713
TI  - CT-guided pericardial drainage catheter placement with subsequent pericardial
      sclerosis.
AB  - Percutaneous drainage of malignant pericardial effusion is an established
      alternative to surgical pericardiotomy and pericardiectomy. We report the
      placement of a pericardial drainage catheter under CT guidance, with subsequent
      pericardial sclerosis. Previously described imaging modalities (fluoroscopy and
      ultrasound) used for the guidance of drain placement are compared and contrasted
      with our use of CT.

PMID- 7622714
TI  - Modified microbiological method for the screening of antibiotics in milk.
AB  - The Bacillus stearothermophilus disc assay is routinely used by the dairy
      industry to screen milk for antibiotic residues. Although the assay detects the
      presence of beta-lactam antibiotics, it does not distinguish cephalosporins from
      other beta-lactam antibiotics. In this study, the B. stearothermophilus disc
      assay was modified to allow it to distinguish parent ceftiofur from other
      antibiotics by incorporation of the enzymes penicillinase and cephalosporinase
      into the assay. The modified B. stearothermophilus disc assay involves
      determining the zone of inhibition of a sample on an agar plate after the plate
      was incubated at 65 degrees C for 2.5 to 3 h as well as determining the zone of
      inhibition after the sample was treated with penicillinase or cephalosporinase.
      Samples in which this zone diameter was > 19 mm and < or = 25 mm were interpreted
      using the data from the primary assay. Samples with zone diameters > 25 mm must
      be diluted 2- to 10-fold and reassayed to obtain a zone diameter > 19 and < or =
      25 mm, for proper interpretation. Samples with zone diameters > or = 16 mm and <
      or = 19 mm must also be reassayed using dilute enzyme solutions for proper
      interpretation. When these modifications of the B. stearothermophilus disc assay
      are used, ceftiofur can be distinguished from ampicillin, amoxicillin,
      penicillin, cephapirin, cloxacillin, novobiocin, and pirlimycin for samples with
      zone diameters > or = 16 mm. This assay cannot, however, separate ceftiofur from
      cefazolin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7622715
TI  - Detection of subclinical mastitis from on-line milking parlor data.
AB  - A model, based on automatically collected data, was developed for detection of
      subclinical mastitis. The logistic regression model was based on the following
      variables: milk electrical conductivity, milk production, parity, and DIM.
      Subclinical mastitis was defined as a minimal period of 1 wk in which the SCC was
      > 500 x 10(3) cells/ml. In contrast, periods were defined as healthy if the SCC
      was < 200 x 10(3) cells/ml. The resulting model had a sensitivity of 55% and
      specificity of 90% for individual milkings. For periods of 14 milkings,
      sensitivity was 54% and specificity 92% when the threshold for that period was >
      6 electrical conductivity signals for high SCC. Based on these test
      characteristics, the model could be used as an initial screening tool in a herd
      with a high incidence of subclinical mastitis. Cows with a signal would have a
      higher probability of being diseased than the total population. In such herds,
      separation of milk from the signaled cows might be a possible management strategy
      to reduce the SCC in the bulk milk tank.

PMID- 7622716
TI  - Comparison of analysis techniques for on-line detection of clinical mastitis.
AB  - Three techniques were compared for analysis of automatically collected data from
      the milking parlor. Mammary quarters showing signs of clinical mastitis were
      compared with randomly selected healthy quarters. Automatic data were analyzed
      from the milking on which the milkers observed clinical mastitis as well as data
      from the two prior milkings. Electrical conductivity of milk was not corrected
      for individual cows. Milking parlor data were preprocessed so that information on
      the electrical conductivity pattern during a milking was retained. Principal
      component analysis was used to verify whether variation in the data was caused by
      mastitis. Performance of logistic regression models for detection of clinical
      mastitis was compared with that of backpropagation neural networks. Variation in
      the quarter data was caused by mastitis. Automatic data from infected quarters
      did not always differ from data from healthy quarters, especially from the two
      prior milkings. The detection performance of the logistic regression model was
      similar to that of the neural networks. When both models were tested on the
      development data, sensitivity was approximately 75%, and specificity was
      approximately 90% at the milking of mastitis observation. Detection results were
      lower for the prior milkings. Therefore, not all incidences of clinical mastitis
      cases could be detected before clinical signs occurred.

PMID- 7622717
TI  - Efficacy of recombinant bovine interleukin-2 as an adjunct to dry cow therapy.
AB  - Recombinant bovine interleukin-2 was tested as adjunct therapy to intramammary
      infusion of antibiotics at drying off. Cows were assigned randomly within three
      commercial herds to either recombinant bovine interleukin-2 or PBS treatment
      groups at drying off. Ninety-five cows received intramammary infusions of 1 mg of
      recombinant bovine interleukin-2 in each quarter immediately preceding
      intramammary infusion of a product for antibiotic therapy of dry cows. Ninety
      four cows received intramammary infusion of 10 ml of endotoxin-free PBS in each
      quarter immediately preceding the antibiotic therapy. Cure rates for IMI present
      at drying off did not differ between cows treated with recombinant bovine
      interleukin-2 and those treated with PBS. Intramammary infusion of recombinant
      bovine interleukin-2 did not affect the rate of new IMI during the dry period.
      Milk production and SCC during the first 3 mo of lactation subsequent to therapy
      did not differ between treatment groups. Intramammary infusion of recombinant
      bovine interleukin-2 was not effective as an adjunct to antibiotic therapy for
      dry cows.

PMID- 7622718
TI  - Cryptosporidium muris: prevalence, persistency, and detrimental effect on milk
      production in a drylot dairy.
AB  - A total of 1746 individual fecal samples were obtained from milking cows during
      three separate visits to a drylot dairy farm. In addition, 1240 fecal samples
      were also obtained from cows in four additional farms. Cryptosporidium muris was
      prevalent in all five herds sampled. Cows that were sampled more than once
      invariably remained in the same shedding category. Cows shedding C. muris oocysts
      produced significantly less milk (approximately 3.2 kg/d). After corrections for
      the effects of age, parity, pen, and DIM in a logistic regression model, mean
      daily milk production was significantly associated with shedding status.

PMID- 7622719
TI  - Bovine somatotropin dose titration in lactating dairy ewes. 1. Milk yield and
      milk composition.
AB  - Seventy-four lactating dairy ewes were injected with recombinant bST
      (sometribove) in a sustained-release formulation. Ewes received 0, 80, 160, or
      240 mg of bST every 14 d from wk 3 to 8 of lactation (part 1) and 0, 80, or 160
      mg of bST every 14 d from wk 11 to 23 of lactation (part 2). Sometribove
      increased milk yield over that of the controls for all treatment groups. The
      increase was largest for the group that was administered 160 mg of bST: milk
      yield was 34.1 and 53.2% and 6% FCM was 36.9 and 51.8% for parts 1 and 2 of the
      study, respectively. Sometribove increased milk fat during part 1 of the study,
      but decreased milk fat during part 2. Protein contents of milk were decreased
      throughout the study. For all group, bST increased the yield of milk constituents
      over that of the controls. When milking frequency was reduced from twice to once
      daily, the difference in milk yield between control ewes and those treated with
      bST was maintained. Neither mastitis incidence nor milk SCC were affected by bST
      treatment. Recombinant bST is efficacious in increasing both actual milk yield
      and 6% FCM over the dose range of 80 to 240 mg/14 d without adverse effects for
      lactating ewes.

PMID- 7622720
TI  - Prediction of body composition of dairy cows at three physiological stages from
      deuterium oxide and urea dilution.
AB  - To develop equations for predicting body composition, mature Holstein cows (n =
      21) were slaughtered at three physiological stages (-7, 63, and 269 d postpartum)
      after consecutive intravenous dosing with urea and D2O. Blood was sampled at 0
      and 12 min after dosing with urea for determination of urea space and from 0 to
      72 h after dosing with D2O. Empty body water and total body water were estimated
      by dilution kinetics for D2O using two- and one-compartment models, respectively.
      At slaughter, body components were ground, sampled, and freeze-dried for chemical
      analysis. Prediction of empty body water by urea space was not an improvement
      over the prediction by body weight alone. Prediction by D2O dilution explained 73
      and 87% of the variation in empty and total body water, respectively. Estimated
      body protein, as determined from empty body water, predicted actual body protein
      with an error of 4.7 kg. Daily DMI explained 84% of the variation in the DM of
      the gastrointestinal tract contents (DM fill). Estimations of empty body fat (R2
      = .85) and empty body energy (R2 = .89) from D2O dilution were capable of
      detecting significant differences in body fat (42.9 kg) and body energy (375
      Mcal) across physiological stages and might be useful for prediction of body
      composition changes during the lactation cycle.

PMID- 7622721
TI  - Influence of roasting or sodium hydroxide treatment of barley on digestion in
      lactating cows.
AB  - Three cannulated, lactating cows were used in a 3 x 3 Latin square design to
      determine the effect of roasting or NaOH treatment of barley on ruminal
      fermentation and site and extent of digestion of nutrients. Experimental
      treatments were rolled barley, roasted (exit temperature, 135 degrees C) and
      rolled barley, and treated with 4% NaOH and 220 L of H2O/tonne of barley. Diets
      also consisted of grass silage and soybean meal. Treatment with NaOH reduced
      concentrations of several AA, starch, and NDF in the barley. Starch digestibility
      in the rumen was lower for barley that was treated with NaOH but was unaffected
      for roasted barley. Digestibilities of N and starch in the small intestine were
      reduced for barley treated with NaOH, but values for rolled and roasted barley
      were similar. Apparent total tract digestibility of starch was reduced for the
      NaOH treated barley. Treatment of barley with NaOH tended to have a detrimental
      effect on feed intake, digestibility, and milk production. Roasting of barley did
      not appear to affect the site or extent of carbohydrate digestion, but roasting
      protected N from ruminal degradation. The protective effect on the carbohydrate
      fraction would be expected to be greater if the grain were cooled prior to
      rolling so that the protein matrix of the starch granule remained intact.

PMID- 7622722
TI  - Nutritive value of dried citrus pulp and its effect on milk yield and milk
      composition of lactating ewes.
AB  - In a digestibility experiment, six adult wethers of the Karagouniko breed were
      used to determine the nutritive value of dried citrus pulp. The rations consisted
      of 800 g of hay and 75, 150, 225, 300, 375, and 450 g of citrus pulp. The
      apparent digestibilities of the DM, OM, CP, ether extract, crude fiber, and N
      free extract for dried citrus pulp were 78.6, 87.2, 52.7, 82.0, 93.2, and 83.1%,
      respectively. Energy content was estimated to be 1.66 Mcal of NE(L)/kg of DM. In
      a second experiment, 26 lactating ewes of the Karagouniko breed were used to
      study the nutrient utilization of dried citrus pulp for milk yield when citrus
      pulp was used as a replacement for cereal grains. The ewes were divided into two
      groups immediately postweaning and fed daily 700 g of alfalfa hay, 300 g of wheat
      straw, and 580 or 550 g of concentrates with or without 30% citrus pulp,
      respectively. The inclusion of citrus pulp in rations for ewes had no significant
      effect on milk yield and composition but decreased the C4 to C10 fatty acids.
      Citrus pulp is a valuable, high energy by-product that can partly replace cereal
      grains in sheep rations without adverse effect on milk yield or composition.

PMID- 7622723
TI  - Evaluation of diets containing supplemental fat with different sources of
      carbohydrates for lactating dairy cows.
AB  - A study was conducted to evaluate the lactational response of high producing cows
      to diets supplemented with fat that contained additional ruminally degradable
      carbohydrate from a molasses plus fat product and dried whey. Forty Holstein cows
      were randomly assigned within lactation group to receive diets containing 2%
      tallow with or without molasses or dried whey wk 4 through 16 postpartum. Cows
      were fed 1) the control TMR of 25% corn silage, 25% alfalfa hay, and 50%
      concentrate mix, 2) the TMR containing fat, 3) the TMR containing molasses and
      fat, or 4) the TMR containing dried whey and fat. Production of milk and 3.5% FCM
      was increased by supplemental fat. Milk protein and fat percentages were not
      affected by supplemental fat with or without molasses or dried whey. The DMI and
      BW were similar for all diets. Production efficiency (3.5% FCM/DMI) was higher
      for cows fed supplemental fat diets, and cows fed tallow alone were more
      efficient than those fed tallow with molasses or dried whey. Tallow did not
      influence ruminal concentrations of various VFA. Molar percentage of butyrate was
      higher for cows fed the TMR containing molasses plus fat or dried whey plus fat
      than for cows fed the TMR containing fat. The TMR containing 2% tallow increased
      milk production, but no economic advantage was derived from inclusion of an
      additional ruminally fermentable carbohydrate as molasses or from dried whey with
      fat.

PMID- 7622724
TI  - Free amino acids in plasma and muscle of high yielding dairy cows in early
      lactation.
AB  - Free AA in plasma and muscle were monitored in 36 dairy cows from 2 wk before
      until 15 wk after parturition. Cows were kept indoors and fed individually. The
      AA concentrations in plasma from 6 to 15 wk of lactation were compared with
      precalving concentrations. Plasma concentrations of Met, Phe, Glu, and Gln
      decreased by 16, 24, 25, and 25%, respectively. The ranking of the essential AA
      according to their decrease in plasma corresponded to the order in which they
      generally appear to be limiting for milk protein synthesis. The decrease of Glu
      and Gln in plasma exceeded that of the essential AA and contrasted strongly with
      all other nonessential AA. The change in the AA profile in muscle from pregnancy
      to lactation resembled that described for the catabolic state in mammals and
      suggests that muscle protein was degraded for supply of AA to the udder, despite
      excess protein and energy supply 15 wk into lactation. In muscle, the decrease in
      the pool of free Gln exceeds 25% and is higher than for any other AA. These
      observations support our hypothesis that Gln is potentially limiting for milk
      protein synthesis in the high yielding dairy cow.

PMID- 7622725
TI  - Evaluating effects of fish meal on milk fat yield of dairy cows.
AB  - Experiment 1 measured the effect of different amounts of dietary fish meal on
      milk yield and composition. Milk fat percentage and yield were decreased by
      increased fish meal intake, but this change was not associated with changes in
      ruminal fermentation patterns. Plasma long-chain n-3 polyunsaturated fatty acids
      were increased as intake of fish meal increased. Ruminal disappearance of DM, CP,
      and lipid in fish meal was measured in situ. Seventy percent of lipid disappeared
      by 8 h. Intraruminal administration of fish oil did not alter ruminal
      fermentation and only slightly changed fatty acid profiles in duodenal digesta,
      plasma, or milk. Duodenal infusion increased plasma n-3 fatty acids but did not
      affect composition of fatty acids in milk. Experiment 2 compared effects of
      dietary fish meal and fish oil on milk production and composition. Fish meal
      increased n-3 fatty acids in plasma compared with those of the fish oil
      treatment. No changes were found in milk yield or composition because of
      experimental treatments. Cows fed fish meal or fish oil differed significantly in
      plasma fatty acid profiles but did not differ in ruminal VFA concentrations or
      milk fat yield.

PMID- 7622726
TI  - Development of metabolic partitioning of energy in young calves.
AB  - Modifications in thermal demand and energy partitioning in newborn calves were
      determined over time via indirect calorimetry. One-week-old calves were fed milk
      replacer at 70 and 110% of the metabolizable energy requirements for maintenance,
      at ambient temperatures of 7.5 or 19 degrees C, over two consecutive but
      separately monitored 7-d balance periods. During wk 1, N digestibility, energy
      digestibility, and energy metabolizability were lower than during wk 2. Heat
      production decreased, but retention of energy and fat increased, between balance
      periods. During wk 1, initial IgG concentration in serum was positively
      correlated with digestibilities of N and energy, and hemoglobin concentration was
      negatively correlated with heat production. Regression analysis revealed that
      predicted basal metabolic rate, efficiency of metabolizable energy use, and
      metabolizable energy requirements for maintenance were lower for wk 2 than for wk
      1. Decreased energy utilization in calves on restricted feedings is related to an
      increase in the utilization of protein as an energy source. Young calves need at
      least 2 wk to adapt to the combination of new environmental temperature and low
      feeding amount. Metabolic partitioning of energy may indicate completion of the
      adaptation stage.

PMID- 7622727
TI  - Nonadditive genetic effects and inbreeding depression for somatic cell counts of
      Holstein cattle.
AB  - A total of 65,491 lactation means of log2-transformed SCC measures were analyzed
      from first lactation Holstein cows in Ontario. Effects of inbreeding on SCC were
      estimated by a nonadditive sire and dam model that included additive, dominance,
      and additive by additive genetic effects and regression of lactation somatic cell
      score on inbreeding coefficients of the cows. Variance components were estimated
      using the tildehat approximation to REML. Solutions were by iteration on data.
      Estimates of heritability for lactation somatic cell score in the narrow sense
      were .165 and in the broad sense were .203. The additive by additive component
      (2.5% of the total phenotypic variance) was almost twice as large as the
      dominance component (1.3%). The regression coefficient of lactation somatic cell
      score per 1% increase of inbreeding was .012. The average increase of the
      population mean of lactation somatic cell score caused by a 10% increase of
      inbreeding coefficient was estimated to be 10.5% of the original phenotypic
      standard deviation of 1.153. The inbreeding depression was thus relatively low,
      but, on average, inbred animals tended to have higher lactation somatic cell
      score. This study provides preliminary evidence that inbreeding is related to
      disease prevalence in large purebred dairy populations.

PMID- 7622728
TI  - Production traits of Holstein cattle: estimation of nonadditive genetic variance
      components and inbreeding depression.
AB  - Additive, dominance, and additive by additive components of genetic variance and
      inbreeding depression were estimated for production traits from a group of
      daughters of young sires from the Canadian Holstein population. First lactations
      of 92,838 cows were analyzed. Three sire and dam models (additive, additive plus
      dominance, additive plus dominance plus additive by additive genetic effects),
      all including regression of the trait on inbreeding coefficient of the cow, were
      used to estimate the effect of inbreeding on production traits. For all
      production traits, heritability in the narrow sense was overestimated with the
      simplest model, in which only the additive effect was fitted. Estimates of
      dominance variance were low for all traits, .9 to 3%. Additive by additive
      components were low for milk, 2.8%, and fat yield, 2.8%, but higher for protein
      yield, 6.8%, and for fat, 9%, and protein percentages, 8.9%. Estimates of
      inbreeding depression for the five traits were similar across all models (-25, 
      .9, and -.8 kg; .05% and .05% per 1% increase in inbreeding for milk, fat, and
      protein production and fat and protein percentages, respectively). More accurate
      estimates of additive effects might be obtained with the inclusion of nonadditive
      effects for genetic evaluation. If the estimation of inbreeding depression is the
      only objective, simple models and small random samples of the population may be
      adequate.

PMID- 7622729
TI  - Fixed yield responses to increased milking frequency.
AB  - Data from 19 literature reports that measured the effect of milking frequency on
      milk yield were summarized. When milking three times daily was compared with
      milking twice daily, the three times daily yield was 3.5 kg/d higher with a 95%
      confidence interval of 3.1 to 3.9 kg/d. Response of fat yield to increased
      milking frequency, from twice daily to three times daily, was 92 g/d, and the 95%
      confidence interval was 67 to 117 g/d. Linear regression analysis showed that no
      relationship existed between twice daily milk yield or fat yield and the amount
      of increase of milk yield or fat yield caused by increasing milking frequency to
      three times daily. This result implied that increased milking frequency from
      twice to three times daily resulted in a fixed increase of 3.5 kg/d of milk yield
      and 92 g/d of fat yield, regardless of the yield for cows milked twice daily.
      Responses of primiparous and multiparous cows were similar in magnitude for twice
      daily versus three times daily milking frequency, suggesting that the separate
      adjustment factors currently used for conversion of three times to twice daily
      equivalents for primiparous and multiparous cows may not be needed if adjustments
      are expressed on the basis of actual yield. The numbers of comparisons of once
      daily and four times daily milking frequency with twice daily milking were
      limited, but showed no relationship with milk yield, and the mean response was 
      6.2 and 4.9 kg/d, respectively. These data also support the concept of a fixed
      yield response to altered milking frequency.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7622730
TI  - Symposium: animal food safety and dairy regulations, now and in the future.
      Animal food safety and dairy regulations, now and in the future: from farm to
      fork, a state perspective.
AB  - The enforcement of dairy and food safety regulations has fallen most heavily on
      the states in the past, and this responsibility will no doubt continue, and even
      expand, in the future. States must be concerned not only about their own state
      laws but also about the impact of increasing federal regulations. The protection
      of sample integrity and chain of custody is an important function of a state
      regulatory program for food safety. Because of increasing demands imposed by new
      technology and food safety requirements, and because of very limited resources,
      states have difficulty maintaining adequate regulatory programs. The future
      challenge will be the ability of states to coordinate regulation, sample
      analysis, and enforcement between federal and state agencies. States must
      continue their roles of ensuring consumers that food is safe and wholesome while
      maintaining viable state food industries.

PMID- 7622731
TI  - Structural features of the 5' flanking region of the caprine kappa-casein gene.

PMID- 7622732
TI  - Interaction of beta-lactoglobulin with retinol and fatty acids and its role as a
      possible biological function for this protein: a review.
AB  - beta-Lactoglobulin is the major whey protein in the milk of ruminants and some
      nonruminants, such as pigs and horses. Although beta-lactoglobulin was first
      isolated 60 yr ago, no function has been definitely ascribed to beta
      lactoglobulin. Recent x-ray crystallographic studies have advanced knowledge of
      the structure of beta-lactoglobulin, which is homologous with that of retinol
      binding protein and lipocalycins; the function of these proteins seems to be
      participation in the transport of small hydrophobic substances. By analogy, this
      protein has been suggested as having a role as a transporter of fatty acids and
      retinol. This review reassesses the function of beta-lactoglobulin in light of
      the large amount of information that has accrued in the last few years. In
      particular, this review concentrates upon studies of the binding of retinol and
      fatty acids to beta-lactoglobulin, including the binding constants and number of
      binding sites, the location of the binding sites, and the influence of chemical
      modifications in the interaction of the protein with both ligands. This study
      also describes studies of the influence of beta-lactoglobulin on several
      biological processes that may be relevant to the possible biological role of this
      protein.

PMID- 7622733
TI  - Cloning and characterization of the galactokinase gene from Streptococcus
      thermophilus.
AB  - The objective of this research was to clone and characterize the galactokinase
      gene (galK) from Streptococcus thermophilus F410. Partially digested genomic DNA
      was cloned into pBR322 and transformed into galK Escherichia coli, and a
      galactose-fermenting transformant was isolated. Restriction analysis revealed
      that the transformant resulted from a Sau3A-HindIII 4.0-kb fragment.
      Galactokinase activity in the recombinant was 10 times that of the parent strain.
      Analysis of the DNA sequence showed the presence of a 1.3-kb open reading frame
      that had high homology with the galK gene from other organisms. A putative
      ribosome-binding site, start and stop codons, and -10 and -35 sequences were
      identified. The predicted protein had a molecular mass of 49 kDa, which
      corresponded to the estimated size of a band apparent by SDS-PAGE. Amino acid
      sequence homologies with other galactokinases ranged from 50 to 62% similarity.
      Northern blots were performed between the galK gene and mRNA from S.
      thermophilus. No hybridization signals were observed for cells grown in glucose,
      but cells grown in lactose or galactose gave moderate and strong signals. The
      results suggest that repression of the galK gene by glucose may be responsible
      for the galactose-releasing phenotype in these strains.

PMID- 7622735
TI  - Adverse parenting and other childhood experience as risk factors for depression
      in women aged 18-44 years.
AB  - 65 women who had experienced a recent major depressive disorder, and 81 women who
      had never been depressed, were recruited from a community probability sample. The
      two groups of women were compared with regard to a number of childhood
      experiences, including parenting style, which was assessed with the Parental
      Bonding Instrument (PBI). When all the childhood factors were considered
      simultaneously in a logistic regression analysis, only low maternal care was
      significantly associated with recent depressive episodes. Low maternal care
      increased the risk of recent major depression approximately 4-fold and the
      estimate of the population attributable risk was 35%. These findings give further
      weight to the contention that adverse parenting in childhood, particularly a
      maternal parenting style typified by low care, is a significant risk factor for
      adult depression.

PMID- 7622734
TI  - Psychiatric episodes in women with young children.
AB  - An historical cohort study was performed. Subjects were 118 pregnant women or
      mothers of children of < 3 years who were assessed at presentation to a
      psychiatric hospital and 5 years later. The relationship of episode onset to
      childbearing (during pregnancy or within 3 months of birth) was derived from
      psychiatric records at presentation and retrospectively determined by interview
      and life-event charting at follow-up. Determining childbearing status from
      records yielded an error rate of 30% compared with the status derived from direct
      interview. A change in diagnosis in the ChildBearing-Related Onset Illness
      (CBROI) category occurred in 50% of subjects. When Research Diagnostic Criteria
      were applied retrospectively to the presenting episodes, 95% of women with CBROI
      had affective disorder diagnoses. Clinicians in our intake setting often missed
      episodes of mania or hypomania in our subjects' histories.

PMID- 7622736
TI  - Clinical characteristics of outpatients with chronic major depression.
AB  - A cross-sectional evaluation of 243 unipolar, nonpsychotic outpatients with major
      depression was conducted. All subjects were diagnosed by RDC with SADS-L
      structured interviews. Diagnoses included RDC primary/secondary, RDC
      endogenous/nonendogenous and Winokur's family-history subtypes. Symptom severity
      was assessed by the 17-item Hamilton Rating Scale for Depression. Chronic
      depression was defined as the current episode of major depression lasting at
      least 2 years, corresponding to DSM-III-R and -IV criteria. Patients with chronic
      depression (n = 64) were compared with those with nonchronic depression (n =
      179). Chronicity was not related to gender, symptom severity, prior length of
      illness, age at onset of illness, RDC endogenous/nonendogenous, RDC
      primary/secondary or Winokur's family-history subtypes. Those with chronic
      depression were older and had fewer major depressive episodes than the nonchronic
      group. That the chronic group had fewer total episodes of depression than the
      nonchronic group, but a similar age at onset, is consistent with the notion that
      patients in a current chronic episode have characteristically longer depressive
      episodes throughout the course of their illness. Those with chronic episodes may
      be subject to psychological, biological and/or sociocultural factors that
      preclude an earlier episode remission for these individuals.

PMID- 7622737
TI  - The upregulation of Na+,K(+)-ATPase pump numbers in lymphocytes from the first
      degree unaffected relatives of patients with manic depressive psychosis in
      response to in vitro lithium and sodium ethacrynate.
AB  - Patients with manic depressive disorder (DSM-III-R bipolar disorder) have an
      abnormality of the Na+,K(+)-ATPase pumps in their lymphocytes: the pump numbers
      do not upregulate to stimulation with lithium and ethacrynate. We have now
      investigated the in vitro adaptive responses of lymphocyte Na+,K(+)-ATPase pumps
      in the first-degree unaffected relatives of patients with a clear history of
      manic depressive disorder. The lymphocytes of the healthy relatives upregulated
      their Na+,K(+)-ATPase pumps normally, suggesting that the abnormal response that
      we have previously observed in patients with the disorder reflects a complex
      relation between the biochemical phenotype and the development of clinical
      symptoms.

PMID- 7622738
TI  - Predicting the course of depression in the older population: results from a
      community-based study in The Netherlands.
AB  - This article is a report on the course of depressive syndromes in a community
      based sample of older subjects in The Netherlands (n = 238). After baseline, the
      course of depression was assessed in five waves of follow-up measurements,
      covering 1 year. 52% of the subjects were never depressed; 16% suffered an
      incident depression, half of which remitted during the study; 8% had a depression
      at the start which remitted during the study; 14% were chronically depressed and
      in 10% the course was variable. Of those depressed at the start of the study, 32%
      remitted without relapse, 25% remitted but relapsed later and 43% were
      chronically depressed. While demographic variables were not predictive, health
      related variables were predictive of both the onset and the course of depressive
      syndromes. Chronicity was associated with recent visits to general practitioners,
      indicating that treatment could have been provided relatively easily in many
      cases.

PMID- 7622739
TI  - Lithium augmentation in a case of renal impairment: risk vs. benefit.

PMID- 7622741
TI  - The implementation of managed care in dentistry.

PMID- 7622740
TI  - An adoption study comparing the prevalence of psychiatric illness in women who
      have adoptive and natural children compared with women who have adoptive children
      only.
AB  - The current study compares the current and lifetime prevalence of affective
      disorder in women who have adopted and have natural children (n = 110) with women
      who only have adopted children (n = 176). There was no difference in lifetime
      prevalence of psychiatric disorder between the two groups and a nonsignificant
      trend for women who had born children to have had a major depressive episode
      during their lifetime 48 (44%) cf 62 (35%). The increased prevalence of
      psychiatric illness in married women with children cannot be explained by the
      biological fact of bearing children. None of the social variables related to
      child-rearing which were examined influenced the lifetime prevalence of
      psychiatric disorder.

PMID- 7622742
TI  - A practitioner's perspective on managed care.

PMID- 7622743
TI  - Dental capitation programs--key decision factors.

PMID- 7622744
TI  - Beware the fourth party.

PMID- 7622745
TI  - Managed care ... it's big, big business.

PMID- 7622746
TI  - American Dental Association managed care resources.

PMID- 7622748
TI  - A policy analyst's view of healthcare reform.

PMID- 7622749
TI  - The need for professional ethics is greater than ever.

PMID- 7622747
TI  - Policy for dentistry's future: the Pew Health Professions Commission.

PMID- 7622750
TI  - Managed medical and dental care: current status and future directions.

PMID- 7622752
TI  - Eosinophil infiltration precedes development of airway hyperreactivity and
      mucosal exudation after intranasal administration of interleukin-5 to mice.
AB  - Recently, we demonstrated that antibody to interleukin-5 (IL-5) prevents the
      infiltration of eosinophils in the respiratory airways and the development of
      bronchial hyperreactivity in an animal model of allergic asthma. In this study we
      investigated the influence of long-term intranasal administration of IL-5 on
      airway responsiveness in vitro, the infiltration of inflammatory leukocytes, and
      mucosal exudation. Mice (BALB/c) received 1 microgram of recombinant human IL-5
      in 30 microliters of saline solution or vehicle alone twice a day for 1, 3, and 7
      days. At 3 and 7 days after IL-5 administration, the number of bronchoalveolar
      lavage eosinophils increased approximately fourfold and sixfold, respectively.
      Blood eosinophil numbers showed a similar increase. In addition, 7 days after IL
      5 treatment, total lung eosinophil peroxidase activity was significantly
      increased by 170% as compared with controls. The maximal responsiveness of the
      trachea in vitro to methacholine was significantly increased by 34%, as compared
      with controls, only at 7 days after IL-5 administration. Furthermore, mucosal
      exudation was also only increased significantly at 7 days after IL-5
      administration. It can be concluded that the IL-5-induced eosinophil infiltration
      precedes the development of airway hyperreactivity and mucosal exudation.

PMID- 7622751
TI  - Establishing practice parameters.

PMID- 7622753
TI  - Selective early increases of bronchoalveolar CD8+ lymphocytes in a LEW rat model
      of hypersensitivity pneumonitis.
AB  - BACKGROUND: The pathogenesis of hypersensitivity pneumonitis (HP) involves cell
      mediated hypersensitivity; various bronchoalveolar T-cell subsets with uncertain
      roles in disease have been reported and implicated in the pathogenesis.
      OBJECTIVES: Previous studies at 72 hours after initial antigen challenges showed
      proportionate increases in T-cell phenotypes. Therefore we tested the hypothesis
      that early events in response to inhaled antigen in a LEW rat model of HP would
      include a disproportionate appearance in bronchoalveolar lavage fluid (BALF) and
      lung parenchyma of a specific T-effector cell responsible for subsequent
      inflammation and that these events could be identified by phenotyping. METHODS:
      We double labeled BALF and parenchymal lung lymphocytes with monoclonal
      antibodies and used flow cytometry to quantitate CD4+ and CD8+ phenotypic subsets
      4 and 24 hours after inhalation of antigen. RESULTS: We found disproportionate
      increases in BALF CD8+ phenotypes. The strongest correlation with pathologic
      findings was for a putative cytotoxic effector (CD8+CD45R-) T lymphocyte.
      CONCLUSION: Meaningful interpretation of lung T-cell phenotype quantitation
      requires studies of kinetics of cellular influxes, timing after antigen
      challenge, and relative comparison with increases in other phenotypes. Any
      pathogenetic role assigned to a phenotype must also await functional studies,
      including cytokine generation and secretion and cell-cell interactions in situ.

PMID- 7622754
TI  - A follow-up study of pulmonary function tests, bronchoalveolar lavage cells, and
      humoral and cellular immunity in bird fancier's lung.
AB  - BACKGROUND AND OBJECTIVE: The long-term outcome of bird fancier's lung appears to
      be variable. The objective of this study is to clarify the sequelae of disease
      process in bird fancier's lung, with special reference to the humoral and
      cellular immune responses after avoidance of direct antigen exposure. METHODS:
      Five patients with bird fancier's lung were studied for various parameters
      including pulmonary function tests, cellular profiles of bronchoalveolar lavage
      (BAL) fluids, determinations of antibodies in BAL fluids and sera, and antigen
      induced proliferation of peripheral and bronchoalveolar lymphocytes during the 5
      years of follow-up. RESULTS: Four of five patients showed improvement in
      pulmonary function, and one showed marked deterioration. This patient's room was
      close to the pigeon coop where her son was breeding pigeons, resulting in low
      grade antigenic stimulation. Three patients demonstrated an increase in CD8+
      cells in BAL fluid, but the remaining two showed an increase in CD4+ cells. The
      levels of IgA antibodies remained unchanged, whereas IgG levels started declining
      after the first 3 years of follow-up. Antigen-induced proliferation of BAL
      lymphocytes from all five patients and blood lymphocytes from four of five
      patients became weaker and gradually approached normal levels. One patient had
      pulmonary fibrosis and showed significant reduction in pulmonary functions but
      elevated reactivity of BAL lymphocytes to pigeon antigens. CONCLUSION: This
      follow-up study demonstrates persistence of sensitized lymphocytes and antibody
      production in the respiratory tract and warrants careful evaluation of patients
      with bird fancier's lung, even after antigen avoidance.

PMID- 7622755
TI  - Fixed drug eruption induced by mepivacaine.

PMID- 7622756
TI  - Effective long-term alpha-interferon treatment for hypereosinophilic syndrome.

PMID- 7622757
TI  - Evaluating exposure to mite allergens.

PMID- 7622758
TI  - Regularly inhaled beta-agonists in stable asthma.

PMID- 7622759
TI  - Allergenic pollen pollinosis in Madrid.
AB  - OBJECTIVE: A 15-year pollen count was performed in the atmosphere of Madrid,
      Spain, to determine the months in which the highest concentrations of allergenic
      pollens occur. METHODS: Pollen counts were done with a Burkard spore trap
      (Burkard Manufacturing, Rickmansworth, Herst., U.K.). The results were
      subsequently compared with results of skin tests in patients with pollinosis born
      and living in and around Madrid. RESULTS: The highest airborne presence (percent
      of total yearly pollen counts, mean of counts from 1979 to 1993) was for Quercus
      spp. (17%); followed by Platanus spp. (15%), Poaceae (15%), Cupressaceae (11%),
      Olea spp. (9%), Pinus spp. (7%), Populus spp. (4%), and Plantago spp. (4%). The
      most predominant pollens from January to April are tree pollens (Cupressaceae,
      Alnus, Fraxinus, Ulmus, Populus, Platanus, and Morus), although these are also
      abudant in May and June (Quercus, Olea, and Pinus spp.). The grass pollination
      period shows a double curve: the first peak occurs from February to April (8% of
      yearly grasses), and the second peak occurs from May to July (90% of yearly
      grasses). Among allergenically significant weeds, the most notable is Plantago;
      in contrast, Rumex, Urticaceae, Cheno-Amaranthaceae, and Artemisia spp. have very
      low concentrations (< or = 2% yearly total pollens). The most significant
      allergenic pollen is that of grasses, with a prevalence of positive prick test
      results of 94%, followed by Olea europaea (61%), Plantago lagopus (53%), Platanus
      hybrida (52%), and Cupressus arizonica (20%). CONCLUSION: The population of
      Madrid is exposed to high concentrations of allergenic pollen from February to
      July, although the most intense period is from May to June. Grass pollens are the
      most important cause of pollinosis in this area.

PMID- 7622761
TI  - 13-Hydroxy-linoleic acid induces airway hyperresponsiveness to histamine and
      methacholine in guinea pigs in vivo.
AB  - The influence of 13-hydroxy-linoleic acid (13-HODE) on the pulmonary resistance
      and dynamic compliance of guinea pigs in vivo was determined. Intravenously
      administered histamine and methacholine caused dose-dependent increases in
      pulmonary resistance and dose-dependent decreases in dynamic compliance in
      anesthetized, spontaneously breathing guinea pigs. Inhalation of an aerosol
      containing 13-HODE (10 mumol/L) enhanced the increases in pulmonary resistance
      observed after administration of histamine or methacholine when compared with the
      respective control animals. The effect of 13-HODE on the increase in pulmonary
      resistance after administration of histamine was dose-dependent. An enhancement
      in the pulmonary resistance was already measured after treatment of guinea pigs
      with aerosols of solutions containing 0.1 mumol/L 13-HODE when compared with that
      of control animals. In contrast, the changes in dynamic compliance were not
      affected by 13-HODE. These results indicate that 13-HODE may play an important
      role in the induction of airway hyperresponsiveness in vivo when it is produced
      or released in significant amounts in the airways.

PMID- 7622760
TI  - Diagnostic criteria for allergic fungal sinusitis.
AB  - Diagnostic criteria for allergic fungal sinusitis have not been established, and
      clinical information consists primarily of isolated case reports. We proposed
      five diagnostic criteria for allergic fungal sinusitis including: (1) the
      demonstration of the characteristic eosinophil-rich allergic mucin visually or
      histopathologically, (2) a positive fungal stain or culture from the sinus at
      surgery, and (3) the absence of immunodeficiency or diabetes. With these
      criteria, seven patients in our metropolitan area with allergic fungal sinusitis
      were identified in a short period. Initial symptoms in our seven patients
      reflected those in 99 case reports in that two children were first seen with
      proptosis, one child and three adults with nasal congestion, and one adult with
      symptoms of chronic sinusitis. All had pansinusitis as shown on x-ray films. Six
      patients were atopic, five had nasal polyposis, and five had Curvularia species
      cultured from the sinuses. Infections with Bipolaris species, asthma, and chronic
      sinusitis were less common in our patients than in those previously reported.
      Recurrent symptoms and additional surgery sometimes resulted when the diagnosis
      was delayed by failure to obtain silver stains for fungus on surgical material
      sent for histopathologic review. Sinus tomography showed that the fungal material
      in the sinuses was of high density, which distinguished it from polyps or
      bacterial exudate. Bony compression, erosion, and rupture of the sinus walls were
      common. Results of IgE levels, precipitin determinations, and eosinophil counts
      were variable in both our patients and those in the literature. On the basis of
      our review, we believe that the simple diagnostic criteria proposed are
      appropriate for both research and clinical purposes.

PMID- 7622762
TI  - Regular use of inhaled albuterol and the allergen-induced late asthmatic
      response.
AB  - BACKGROUND: We have recently demonstrated that a 2-week course of inhaled
      albuterol 200 micrograms four times daily caused a near doubling of the allergen
      induced early asthmatic response. We hypothesized that this might extend to the
      more clinically relevant late asthmatic response. METHODS: We studied 11 patients
      with atopic asthma who were free from all medications including inhaled beta 2
      agonists for more than 4 weeks. We performed a double-blind, random-order,
      crossover study, comparing the effect of 1-week treatment periods of albuterol
      200 micrograms four times daily and placebo 2 puffs four times daily on the early
      and late asthmatic responses to the same dose of allergen. RESULTS: Regular use
      of albuterol did not influence the baseline forced expiratory volume in 1 second
      (FEV1) (3.40 vs 3.42 L, p = 0.84) or the baseline methacholine provocative
      concentration causing a 20% fall in FEV1 (PC20) (geometric mean, 2.4 mg/ml vs 1.9
      mg/ml, p = 0.38). However, all aspects of the allergen-induced asthmatic response
      were increased. After the 1-week albuterol treatment, the early asthmatic
      response was slightly greater (21.1% vs 17.9% FEV1 fall, p = 0.26), the late
      response was greater (23.1% vs 13.2% FEV1 fall, p = 0.0027), and the allergen
      induced increase in airway responsiveness (change in log methacholine PC20) was
      greater (0.37 vs 0.20, p = 0.045). CONCLUSIONS: One week of albuterol treatment
      (200 micrograms four times daily) increased the late asthmatic response and
      allergen-induced increase in airway responsiveness. This suggests that the
      combination of regular use of inhaled beta 2-agonist and allergen exposure may
      cause more airway inflammation than allergen exposure alone.

PMID- 7622763
TI  - Clinical equivalence of a novel non-chlorofluorocarbon-containing salbutamol
      sulfate metered-dose inhaler and a conventional chlorofluorocarbon inhaler in
      patients with asthma.
AB  - BACKGROUND: New formulations of non-chlorofluorocarbon-containing propellants for
      pressurized metered-dose inhaler delivery systems must be developed in response
      to the forthcoming ban on chlorofluorocarbon (CFC) production. OBJECTIVE: This
      study compared the bronchodilator effects of 100, 200, and 300 micrograms (base
      equivalent) of salbutamol in a novel CFC-free propellant system (Airomir in the
      3M CFC-Free System; 3M Pharmaceuticals, St. Paul, Minn.; 108 micrograms of
      salbutamol sulfate or 90 micrograms of salbutamol base equivalent per inhalation)
      with that of 100 and 200 micrograms of salbutamol base in a conventional CFC
      propellant system (Ventolin, CFC-11/12; Allen and Hanburys, Division of Glaxo
      Inc., Research Triangle Park, N.C.; 90 micrograms of salbutamol base per
      inhalation) and placebo. METHODS: Twenty-six patients with chronic, stable
      asthma, who had a forced expiratory volume in 1 second (FEV1) between 50.0% and
      75.0% of predicted normal value, entered this randomized, double-blind, double
      dummy, 6-period, crossover study. FEV1 was measured before and at multiple time
      points (ranging from 10 to 480 minutes) after administration of one, two, and
      three inhalations of salbutamol/CFC-free (100, 200, and 300 micrograms); one and
      two inhalations of salbutamol/CFC (100 and 200 micrograms); and placebo. Safety
      parameters included adverse events, heart rate, blood pressure, physical
      examinations, electrocardiograms, and clinical laboratory tests. Parametric
      analysis of variance models appropriate for a 6-period crossover design were
      used, along with multiple comparisons according to Tukey's method. RESULTS: All
      active treatments produced significantly (p < 0.0001) greater bronchodilation
      than placebo. The bronchodilator effect, as measured by FEV1 (peak percent
      change, peak as a percent of predicted value, duration, and area under the curve)
      after two inhalations of salbutamol/CFC-free was clinically comprable to two
      inhalations of salbutamol/CFC, with no clinically meaningful differences in
      safety parameters between the two delivery systems or between different dose
      levels. CONCLUSION: These results suggest that salbutamol/CFC-free may offer a
      suitable alternative for salbutamol/CFC when the need arises to change from CFC
      containing salbutamol products.

PMID- 7622764
TI  - Preferential recruitment of activated, memory T lymphocytes into skin chamber
      fluids during human cutaneous late-phase allergic reactions.
AB  - To determine whether activated memory T lymphocytes (CD3+CD4+CD45RO+CD25+HLA-DR+)
      preferentially accumulate during the cutaneous IgE-dependent late-phase response,
      we challenged 10 atopic patients with allergen and monitored the cellular influx
      for 12 hours with a skin blister chamber model. Four patients with allergy were
      also challenged with irrelevant allergen in control experiments. Histamine
      release and the size of the cutaneous late-phase response were measured. Light
      microscopic analysis and phenotyping of recruited and blood lymphocytes were
      performed with immunofluorescence and flow cytometry. Antigen challenge induced
      significant histamine release, a macroscopic late-phase response, and significant
      cellular influx in the appropriately challenged patients with allergy but not in
      control subjects. In the control group, only limited phenotypic analyses could be
      performed, which demonstrated an equivalent percentage of CD3+CD4+ cells in the
      chamber fluids compared with blood. In contrast, a higher proportion of CD4+ T
      lymphocytes and a lower proportion of CD8+ T lymphocytes accumulated in chamber
      fluids during the late-phase response compared with that present in blood. The
      vast majority of the recruited T lymphocytes expressed a memory phenotype
      (CD45RO+) with enhanced percentages of CD25+ and HLA-DR+ cells. Also, these cells
      had increased levels of very late antigen-4 (CD49d/CD29) and reduced levels of L
      selectin compared with the same cells in blood. These results demonstrate that
      allergen challenge of the skin in patients with allergy leads to the preferential
      accumulation of activated, memory T lymphocytes. The mechanism by which these
      cells are selectively recruited during cutaneous allergic inflammation remains to
      be determined.

PMID- 7622765
TI  - Evaluation of variables influencing the outcome of the atopy patch test.
AB  - BACKGROUND: The number of positive atopy patch test (APT) results in patients
      with atopic eczema (AE) varies in different studies, probably because of
      different test techniques. Variables that may influence the outcome of the APT
      were evaluated. METHODS: APTs were performed in 84 patients with AE, 30 control
      patients with atopic disease, and 85 healthy volunteers, with house dust mite and
      grass pollen allergens in concentrations of 100, 1000, 10,000, and 100,000
      allergenic units/ml. The influence of 0, 10, or 20 tape strippings was
      investigated. The tests were performed on the back and/or the antecubital fossa
      and evaluated after 20 minutes and 24, 48, and 72 hours. In all patients the
      total and specific serum IgE levels were measured. RESULTS: The maximal number of
      positive APT results were obtained under the following conditions: an allergen
      concentration equal to 10,000 allergenic units/ml, 10 tape strippings and
      readings at 24 and 48 hours. Positive APT results were observed in five of 30
      control patients with atopic disease and in none of 85 healthy volunteers.
      Statistically significantly higher total and allergen-specific serum IgE levels
      were found in the group of patients with AE with positive APT results.
      CONCLUSIONS: We recommend the previously described conditions to get an optimal
      method for APT. The correlation between the APT and the total and specific serum
      IgE suggests an important role for IgE in the reaction mechanism behind the APT.

PMID- 7622766
TI  - Immunochemical characterization of recombinant and native tropomyosins as a new
      allergen from the house dust mite, Dermatophagoides farinae.
AB  - BACKGROUND: Two predominant mite species, Dermatophagoides farinae and
      Dermatophagoides pteronyssinus, are responsible for the immediate
      hypersensitivity reaction. Although a large number of antigens and allergens was
      detected in a whole mite culture extract, only the major allergens of Der I and
      II groups have been extensively studied. Much information on other important
      allergens remains to be accumulated. METHODS: A new allergen complementary DNA
      (cDNA) clone was isolated from a D. farinae protein cDNA library. The expression
      product of the cDNA and native tropomyosin from D. farinae were purified,
      characterized, and evaluated. RESULTS: An amino acid sequence deduced from the
      cDNA clone revealed significant homology with tropomyosins conserved in a wide
      range of animals. The amino acid sequences of two fragments obtained by
      degradation of the purified protein with cyanogen bromide coincided completely
      with the corresponding portions of the deduced amino acid sequence. The native
      tropomyosin reacted with specific IgE in the 31 sera tested at a high frequency
      (80.6%), comparable to that of Der f I (90.3%) and Der f II (74.2%). CONCLUSIONS:
      The cloned cDNA encodes tropomyosin. The high binding response of specific IgE
      antibodies to recombinant and native tropomyosins demonstrates that mite
      tropomyosin is an additional important allergen in house dust mite.

PMID- 7622767
TI  - Antigen presenting cell-independent cytokine and spontaneous in vitro IgE
      production in patients with atopic dermatitis: increased interferon-gamma
      production and lack of effects of in vivo low-dose interferon-gamma treatment.
AB  - Atopic dermatitis is characterized by elevated serum IgE concentrations and
      dysregulation of T-lymphocyte function. To examine the pattern of cytokine
      production associated with elevated IgE levels, phorbol ester plus ionomycin
      stimulated production of interleukin (IL)-4, IL-5, and interferon-gamma (IFN
      gamma) by blood mononuclear cells from 16 patients with atopic dermatitis was
      compared with that of 18 healthy subjects. Spontaneous in vitro IgE production
      was also studied longitudinally in patients receiving placebo or daily treatment
      with 0.05 mg/m2 IFN-gamma. Spontaneous in vitro IgE production and mitogen-driven
      IL-4 and IFN-gamma synthesis did not differ when patients were receiving
      interferon treatment compared with no treatment. Furthermore, ionomycin plus
      phorbol ester-stimulated mononuclear cells from patients with atopic dermatitis
      produced less IL-4 and more IFN-gamma than did cells from healthy subjects. IL-5
      production by cells from patients with atopic dermatitis did not differ from that
      of cells from healthy subjects. The ratio of IL-4 to IFN-gamma produced in vitro
      was significantly lower (p = 0.04) in the cells of patients with atopic
      dermatitis (0.9) as compared with those of healthy subjects (2.7). The findings
      suggest that when circulating T cells are stimulated under antigen presenting
      cell-independent conditions, atopic dermatitis is not characterized by the shift
      in the reciprocal relationship between IL-4 and IFN-gamma production, which has
      been postulated to explain the pathogenesis of IgE elevation and the therapeutic
      action of IFN-gamma in patients with atopic dermatitis.

PMID- 7622768
TI  - Expression of interleukin-4 and interleukin-5 mRNA in developing cutaneous late
      phase reactions.
AB  - The stimuli for the accumulation and activation of eosinophils, which are
      prominent components of IgE-mediated allergic late-phase reactions (LPRs), are
      not defined. Messenger RNA for interleukin-5 has been found in lymphocytes
      present in biopsy specimens of skin obtained during LPR 24 hours after antigen
      challenge. However, it is not known whether interleukin-5 is present to attract
      or activate the eosinophils that accumulate during the first 6 hours after
      antigen challenge when cutaneous LPRs are developing. Using reverse transcription
      polymerase chain reaction, we have found mRNA for interleukin-5 in biopsy
      specimens obtained from control challenge sites nor in specimens from sites of
      antigen challenge of nonreactive subjects. We also found mRNA for interleukin-4
      in these sites developing LPR. This pattern suggests that these cytokines may be
      important in eosinophil accumulation and activation during developing LPR. These
      findings are of considerable clinical relevance because the eosinophils in LPR
      are postulated to play major pathogenic roles in chronic allergic diseases.

PMID- 7622769
TI  - [Role of pulsed color Doppler in the presurgical evaluation of pelvic masses].
AB  - OBJECTIVES: To evaluate the prognostic value of colour pulsed Doppler in a
      prospective study of pelvic masses comparing resistance index, serum CA 125 and
      echographic findings with histology results. METHODS: A prospective study
      included 91 patients examined at the Gynaecology-Obstetrics unit at the Croix
      Rousse Hospital. Pelvic masses were classified as benign or malignant tumours on
      the basis of echography findings. Serum CA 125 was assayed before surgery;
      malignancy was suspected for levels above 35 IU/ml. A colour pulsed Doppler
      examination was performed at the same time as the echography. Tumours were
      classed as vascular or non-vascular. A resistance index < or = 0.5 was considered
      pathological. The sensitivity and specificity of each examination were
      determined. The ROC method was used to determine best threshold level for the
      resistance index. Finally, the performance of the 3 tests was analyzed with the
      Metha algorithm. All patients underwent exeresis of the pelvic mass. The
      pathology report was taken as the definitive diagnosis. RESULTS: A total of 80
      benign masses were analyzed. Thirty percent of them had a vascularization
      detectable with colour pulsed Doppler. One case of dermoid cyst has a resistance
      index below 0.5. Echography gave doubtful results in 6 cases and CA 125 was
      higher than 35 in 9. There were 10 cancers of the ovary and 1 borderline tumour.
      Four had a resistance index above 0.5, but the operator reported a hypervascular
      tumour in all cases. Three of these tumours had been classified as benign after
      echography and CA 125 was < 35 IU in 4. The mean resistance index for benign
      tumours was 0.71 compared with 0.41 for malignant tumours. The sensitivity of
      colour pulsed Doppler was 0.66 with a specificity of 0.99 when the resistance
      index was below 0.5. For an index considered to be pathological; below 0.76, the
      sensitivity was 100% and the specificity 85%. CONCLUSIONS: Colour pulsed Doppler
      gives valuable pre-operative information on ovarian masses. Its performance is as
      least as good as CA 125 assay or echography.

PMID- 7622770
TI  - [Epithelial cancers of the ovary. Recent trends].
AB  - Ovarian carcinomas constitute the major cause of the mortality and morbidity in
      gynaecology. Most ovary carcinomas are epithelial tumours. Our understanding of
      ovarian cancerogenesis has been hampered by the lack of a well defined precursor
      lesion, the lack of knowledge about tumour progression, and by the relative
      inaccessibility of the ovaries in the abdominal cavity. Recent studies using
      experimental models allow us to better define the fundamental mechanisms of
      carcinogenesis from the serous ovarian cells and of invasion of the
      abdominopelvic cavity by proximity. This review article tries to update on
      epidemiology, genetic syndromes, biology, screening, and therapy of these
      epithelial tumours, and about the new directions taken by basic and clinical
      research. We will present data concerning oncogenes and tumour suppressor genes
      involved in epithelial ovarian tumours, regulation of tumour cells by growth
      factors, genes involved in tumour invasion, and mechanisms used by the cancer
      cell to resist to therapies. Non-epithelial ovarian tumours will not be examined
      in this manuscript.

PMID- 7622771
TI  - [Comparative study of ofloxacin+amoxicillin-clavulanic acid versus
      doxycycline+amoxicillin-clavulanic acid combination in the treatment of pelvic
      Chlamydia trachomatis infections].
AB  - OBJECTIVE: To evaluate the efficacy and safety of ofloxacin+coamoxiclav versus
      doxycycline-coamoxiclav in the treatment of chlamydial pelvic infections. DESIGN:
      An open, comparative, randomised, monocentric study. SUBJECTS: A hundred and
      eighteen patients (85 endometritis and 33 salpingitis) were included. Clinical,
      laparoscopic and bacteriological assessments were performed before treatment.
      30.4% of salpingitis were considered as severe (COGIT score > 6). 25.4% of acute
      pelvic infections were only caused by Chlamydia trachomatis. TREATMENT: A hundred
      and eighteen patients were treated orally with 3 week combination ofloxacin (200
      mg b.i.d.) + coamoxiclav (1 g b.i.d.) (n = 60) or with a 6 week coamoxiclav (1 g
      b.i.d.) + doxycycline (100 mg b.i.d.) (n = 58). RESULTS: Oral combination
      ofloxacin-coamoxiclav is as effective as oral combination doxycycline+coamoxyclav
      with respectively 96.7% versus 96.6% and 100% versus 98.4% satisfactory clinical
      et bacteriological results.

PMID- 7622772
TI  - [Non-Hodgkin malignant lymphomas of the uterus. Two cases. Review of the
      literature].
AB  - The initial manifestations of two cases of non-Hodgkin malignant lymphoma of the
      uterine body were a cauda equina syndrome in one and bowel occlusion in the
      other. A review of the literature on isolated non-Hodgkin malignant lymphomas of
      the uterine body was discussed.

PMID- 7622773
TI  - [Pelvic myxoid liposarcoma. A case report].
AB  - Myxoid liposarcoma is a rare soft tissue tumour. The authors report one case of
      retroperitoneal tumour discovered during pregnancy, which recurred after initial
      surgery. Clinical features, clinical course and prognosis of this disease are
      examined together with management procedures.

PMID- 7622774
TI  - [Malignant melanoma of the vagina. Two case reports. Review of the literature].
AB  - OBJECTIVE: Report the diagnosis and therapeutic approach in two cases of primary
      malignant melanoma of the vagina. RESULTS: Malignant melanoma is rarely localized
      in the vagina, resulting from the malignant transformation of an ectopic
      melanocyte during menopause. The clinical diagnosis is often made in an advanced
      stage with a variable degree of pigmentation, usually on the anterior aspect of
      the vagina. Surgical exeresis should be extensive with a 1-cm safety margin.
      Radiotherapy may be effective as a complementary treatment for limited surgery or
      as first intention therapy aimed as improving local control before surgery.
      CONCLUSION: Locoregional relapse occurs in 60% of the cases, emphasizing the
      importance of local treatment. The prognosis is unfavourable with a 23 month mean
      survival. Total survival at 5 years is only 17%.

PMID- 7622775
TI  - [Iliac vein stenosis caused by intrauterine device migration].
AB  - There have been no other cases of migration of an intrauterin device reported to
      have caused venous compression. In the case reported here, the intrauterin device
      was removed surgically together with a portion of the damaged vein. A venous
      graft from the internal jugular vein was performed. The mechanisms of
      perforations, different localizations are discussed and diagnostic and
      therapeutic approaches are proposed.

PMID- 7622776
TI  - [Pseudo-unicornuate uterus. Diagnostic difficulties and obstetrical
      complications. Nine cases].
AB  - Diagnostic procedures used in 9 cases of pseudo-uterus unicornis were presented.
      There are no manifestations of this malformation excepting during pregnancy and
      rare episodes of uncontrollable dysmenorrhoea. If pregnancy develops in the
      rudimentary cornis, major complications require hemihysterectomy.

PMID- 7622777
TI  - [Prenatal prevention of infant respiratory distress syndrome. 1st part:
      experimental data and pharmacological treatment].
AB  - Pulmonary maturation and growth are two time-related interdependent phenomena.
      The main regulatory mechanisms of pulmonary maturation are complex and the role
      of epithelial-mesenchymal interrelationship appear to be determinant in the
      phenomena leading to morphological growth of the lung and in cellular
      differentiation of the epithelium during development. At an early stage of
      morphological development of the fetal lung, endogenous hormones do not directly
      affect epithelial differentiation but modulate the expression of genes coding for
      surfactant. Later surfactant production responds to multihormone regulation. Some
      of these hormones or growth factors (steroids, oestradiol, prolactin, thyroxine,
      epidermal growth factor, fibroblast pneumocyte factor) are powerful stimulators,
      favoring biochemical development of the fetal lung. Inversely, other factors
      (insulin, androgens) limit the production of surfactant. Glucocorticoids play a
      specific role (stimulation of morphologic and biochemical development of the
      lung) and potentialize the stimulating effect of other factors. A good
      understanding of these mechanisms is essential before introducing treatments
      stimulating natural processes as closely as possible. Experimental results on the
      use of lung maturation induction, especially with glucocorticoids, have been
      quite promising. Combining thyroid hormones and thyrotropin-releasing hormone
      appears to be an interesting proposal, as is the use of growth factors such as
      epidermal growth factor.

PMID- 7622778
TI  - [Prenatal prevention of infant respiratory distress syndrome. 2nd part: clinical
      applications and indications].
AB  - Two types of sometimes complementary therapeutic strategies can be developed to
      prevent infant respiratory distress syndrome antenatally. The first is to
      administer a treatment aimed at accelerating the maturation process of fetal lung
      tissue in women at risk of premature birth. This is the only strategy with a goal
      of antenatal treatment. The second method is to optimize neonatal care,
      particularly with exogenous surfactants. The use of corticosteroids during the
      antenatal period has been well studied and is known to be effective with a 50%
      reduction in the risk of the syndrome before 34 weeks gestation. Prenatal
      morbidity and mortality are decreased without major adverse effects. Based on a
      limited number of cases, TRH-corticosteroid combination probably gives better
      results with no predictable unfavourable neonatal consequences. The synergic
      action of antenatal treatments, completed with exogenous surfactants at birth, is
      one of the fundamental aspects of care for very premature infants (< 28 weeks
      gestation).

PMID- 7622779
TI  - ["Prune belly" syndrome. Etiopathogenesis and prenatal diagnosis. A case report].
AB  - Prune belly syndrome was diagnosed early in the antenatal period. Renal function
      was evaluated on the basis of bladder puncture results performed at 18 weeks
      gestation due to urethral atresia, suggesting a possible pathogenesis mechanism.
      Recent pathogenic data and the relationship with antenatal diagnosis are
      discussed.

PMID- 7622780
TI  - [Cyclophosphamide during pregnancy: a safe prescription].
AB  - Cyclophosphamide is an alkylating agent used to treat haematologic malignant
      diseases and multisystem diseases with progressive glomerulonephritis. It is
      rarely prescribed during pregnancy. We report a case of Henoch-Schonlein purpura
      discovered at the end of the first trimester of pregnancy. Despite steroid
      therapy, glomerulonephritis worsened and 100 mg/day cyclophosphamide per os was
      administered from 28th week till delivery. The infant, prematurely born, was
      normal and did not have any haematological disorder. Congenital malformations are
      often reported (5 out of 19 newborns exposed in utero to cyclophosphamide), but
      in all those cases, there was another potentially teratogenic agent: either
      radiotherapy or another antineoplastic drug. Therefore, if mother's life is in
      jeopardy, cyclophosphamide therapy should be given and not postponed.

PMID- 7622781
TI  - [Transabdominal amnio-infusion facilitates external version maneuver after
      initial failure. Six successful attempts].
AB  - External version was successful after initial failure in 6 cases after
      transabdominal amnio-infusion. Filling the uterine cavity by amnio-infusion with
      700 to 900 ml saline solution at 37 degrees C facilitated cephalic presentation
      in these 6 cases. In each case, a prior version attempt had been unsuccessful.
      Amnio-infusion was performed under continuous sonographic monitoring before a
      second attempt the next day. The clinical situation was different in the 6 cases
      which all terminated by normal cephalic delivery. Two patients were first parity,
      another has a single uterine scar, 3 had a normal pelvis (Magnin > 23), one a
      narrow pelvis (Magnin = 22.7) and 2 had a pelvis considered pathological (Magnin
      < 22). The main goal of this preliminary study was to evaluate the feasibility
      and safety of this new indication for transabdominal amnio-infusion. This new
      indication should be evaluated by several clinical trials, but it would new
      appear reasonable to propose transabdominal amnio-infusion in patients with a
      pathological pelvis and/or a single cicatricial uterus.

PMID- 7622782
TI  - [Perinatal mortality and preeclampsia/eclampsia: influence of HELLP syndrome on
      the primigravida].
AB  - Perinatal losses have been studied in 37 pre-eclamptic/eclamptic patients: 13 of
      them exhibited a HELLP syndrome. Only 23 newborns survived (62.5%); after
      deduction of 4 pregnancies of less than 28 weeks, the perinatal mortality was
      27%. Comparison with the local perinatal mortality showed a 6-fold higher risk
      for the fetus when pregnancy was complicated by pre-eclampsia/eclampsia,
      regardless of a superimposed HELLP syndrome. For reasons beyond our understanding
      the fetal losses with HELLP syndrome are much higher in primigravidae.

PMID- 7622783
TI  - [The gynecologist-obstetrician and Jehovah's Witnesses].

PMID- 7622784
TI  - [Vascular modifications in uteri exposed to distilbene].

PMID- 7622785
TI  - Efficiency of the salt flotation technique in the recovery of Ascaris
      lumbricoides eggs from the soil.
AB  - The efficacy of the salt flotation technique using saturated solutions of sodium
      nitrate (specific gravity 1.30) and zinc sulphate (specific gravity 1.16) for
      separating Ascaris lumbricoides eggs from clay, loamy and sandy soils has been
      investigated. Ten samples of each of the egg concentrations of 100, 500, 2500,
      5000 and 10,000 eggs/25 g of soil were used for each soil type. Using T-test and
      ANOVA, the number of eggs recovered from sand was significantly higher than from
      loam and the number from loam significantly higher than from clay. With sodium
      nitrate, the maximum egg recovery rate was 25.04% from sandy soil at a
      concentration of 500 eggs/25 g soil while with zinc sulphate it was 13.88% also
      from sandy soil and concentration of 500 eggs/25 g soil. While the number of eggs
      recovered increased with soil egg concentration, the percentage of eggs recovered
      is inversely proportional to egg concentration. The number of eggs recovered with
      sodium nitrate was significantly higher than with zinc sulphate solution in the
      three soil types.

PMID- 7622786
TI  - Oxidation and reduction of cytochrome c by mitochondrial enzymes of Setaria
      cervi.
AB  - A mitochondria-rich fraction isolated from the cuticle-hypodermis-muscle system
      of Setaria cervi, a bovine filarial parasite, possessed substrate-coupled
      cytochrome c reductases and cytochrome c oxidase in appreciable activities. All
      these activities were located predominantly in the membranes. NADH-coupled
      cytochrome c reductase was more prominent than NADPH- and succinate-coupled
      reductases. All the three reductases exhibited marked sensitivity to rotenone and
      antimycin A. Salicylhydroxamic acid strongly inhibited succinate requiring
      reductase and cytochrome c oxidase, but the other two reductases only mildly.
      Sodium azide activated the reductases but substantially inhibited the oxidase
      activity. Potassium cyanide activated the succinate requiring reductase but did
      not cause any noticeable change in the activities of pyridine nucleotide linked
      reductases. Anthelmintics also influenced these activities but no definite
      correlation could be drawn regarding their mode of action.

PMID- 7622787
TI  - Schistosoma japonicum and S. mansoni: comparison of larval migration patterns in
      mice.
AB  - Mice were infected percutaneously with cercariae of Schistosoma japonicum or S.
      mansoni and parasites recovered by tissue-mincing from the skin or lungs or by
      perfusion of the mesenteric veins. S. japonicum had a narrow peak of recovery (up
      to 30%) from the lungs 3 days after infection, whereas lung recovery of S.
      mansoni peaked only on day 6 and levelled off during the following week.
      Infection with S. japonicum induced lung petechiae, but only after most of the
      parasites had left the lungs. The axillary lymph nodes draining the infection
      site increased in weight after infection and this effect was much greater and
      longer with S. mansoni than with S. japonicum. S. japonicum was perfusable from
      the mesenteric veins earlier (from day 3 onwards) and in higher number (40-60%
      from days 6 to 10) than S. mansoni (20% on day 20). The percentage of cercariae
      developing to adult worms was 57% for S. japonicum and 33% for S. mansoni. The
      data demonstrate that S. japonicum might escape from local tissue reactions in
      the skin and lungs and, due to its rapid migration, might induce only poor
      lymphocyte proliferation. As a possible consequence, S. japonicum may establish
      more efficiently in mice than S. mansoni.

PMID- 7622788
TI  - Prevalence and habitat specificity of steinernematid and heterorhabditid
      nematodes isolated during soil surveys of the UK and the Netherlands.
AB  - Entomopathogenic nematodes were isolated from soil samples collected during three
      separate surveys, two in the United Kingdom and one in the Netherlands. The
      nematodes were identified by their restriction fragment length polymorphisms on
      hybridization of Southern blots with a ribosomal DNA repeat unit clone. A total
      of eight steinernematid species/RFLP types and two heterorhabditids were
      isolated. The distributions of the majority of these species/RFLP types were
      significantly different between the three surveys and some of the species
      displayed a close association with certain habitat types.

PMID- 7622789
TI  - Higher levels of passive compared with active immunity in rats immunized with
      larval antigens of Schistosoma mansoni.
AB  - We have previously shown that it is the lung stage schistosomulum which is both
      the inducer and the target of immunity in rats vaccinated with irradiated
      cercariae but that rats can also be partially protected by immunization with
      detergent extracts of mechanically-transformed schistosomula. In the present
      study we therefore compared the immunogenicity of these and intermediate
      schistosomular stages. In the first experiment low levels of protection (13-24%)
      were induced by extracts of mechanically-transformed schistosomula cultured for 3
      hours or 2 days but not by extracts of lung schistosomula. In a repeat experiment
      insignificant levels of protection were induced by extracts of 3 h schistosomula
      and lung schistosomula were again non-protective. Nevertheless, high levels of
      anti-schistosomula antibodies were demonstrated and sera from actively immunized
      rats conferred significant passive protection in five out of six trials. The
      levels of protection conferred by passive immunization (26-51%) were in each case
      higher than the levels of protection demonstrated in the respective serum donor
      groups, showing that some form of immunological blockade suppression is operating
      to prevent expression of protective immunity in the actively immunized rats.

PMID- 7622790
TI  - Analysis of migration success of Onchocera lienalis microfilariae in the
      haemocoel of Simulium vittatum.
AB  - Migration success (i.e. the proportion of worms that reach the thorax) of
      Onchocerca lienalis microfilariae (mf) in the haemocoel of Simulium vittatum was
      studied by inoculating mf into the posterior abdomen, and recording their
      distribution in the blackfly body at predetermined time points. Mf arrive into
      the thorax by active locomotion rather than by drifting in haemolymph currents.
      Migration into the thorax was completed by 12 h post inoculation (pi) but was not
      continuous throughout this period. Migration proceeded in two phases; the first
      occurred 0-2 h pi and the second at 6-12 h pi. Overall, migration success 12-24 h
      pi was only 36%, indicating that a substantial number of mf failed to reach the
      thorax, either because they were eliminated by the fly's defensive response or
      because they remained in the abdomen. Migration success was density independent.
      Mf that arrive into the thorax within 2 h pi did not differ in their migration
      potential from mf that remained in the abdomen at this time. In flies where more
      mf migrated successfully there was lower mf loss, indicating that migration
      success was linked to mf loss. Moreover, the proportion of mf in the thorax was
      not correlated with mf loss, suggesting that mf loss affected the number of mf
      that migrated successfully, rather than the reverse causal relationship.

PMID- 7622791
TI  - Faecal egg output, contamination of pastures and serum pepsinogen concentrations
      in heifers with natural gastrointestinal nematode infections in north-west Spain.
AB  - In 1988, 1989 and 1990 second year grazing heifers, naturally infected with
      gastrointestinal nematodes, were separated into two groups, one of which was
      treated orally with albendazole. In 1988 and 1989 treatment was administered
      immediately after parturition (February), and in 1990 during the last term of
      pregnancy (December). Both treated and control animals were grazed on separate
      plots in a rotational system. Maximum faecal egg counts were observed around
      parturition, except in 1990, when treatment was given at the end of gestation.
      The main genera identified were Cooperia, Trichostrongylus, Ostertagia and
      Oesophagostomum. The number of Ostertagia larvae in the treated groups increased
      from 1989 to 1990, while the others decreased. Pasture contamination with third
      stage larvae (L3) was lower on the plots grazed by treated heifers. Maximum
      numbers of L3 were found in autumn, at the end of winter, and at the beginning of
      spring. Mean serum pepsinogen concentrations were significantly higher in the
      untreated groups. This concurs with the pattern for L3 on pasture. The trial
      shows that if a single treatment against gastrointestinal nematodes is carried
      out, and the animals remain on contaminated pastures, the parasitic load tends to
      level out after 4-5 months under favourable climatic conditions. However, the
      percentages of nematode genera occurring in the new populations may differ from
      those in the original infection.

PMID- 7622792
TI  - Life history of the nematode Rhabdochona hellichi, a parasite of the barbel in
      the Jihlava River, Czech Republic.
AB  - From April 1992 until June 1993, the seasonal dynamics of Rhabdochona hellichi
      (Sramek, 1901) in its definitive host, the barbel (Barbus barbus), was studied in
      the Jihlava River (the Danube basin), Czech Republic. The parasite occurred in
      barbel throughout the year (overall prevalence 93% and intensity of infection 1
      1384 [mean 78] nematodes per fish), but there were distinct seasonal fluctuations
      in prevalence and mean intensity values associated with the parasite's seasonal
      cycle of maturation. Prevalence was very high (usually 100%) during most months
      of the year, while lowest values were recorded in August and October. The highest
      values of mean intensity occurred in April. Both prevalence and mean intensity
      values increased with the body length of the hosts. The parasite exhibited a
      distinct annual cycle of maturation with egg-producing females present only from
      June until August, whereas larvae occurred in barbel mostly from September until
      April of the next year. Trichopteran (caddis-fly) larvae of the genus Hydropsyche
      (H. angustipennis and H. pellucidula) were found as natural intermediate hosts of
      R. hellichi (prevalence 4%, intensity 1-10 nematode larvae). The strictly
      seasonal maturation of this nematode may be associated with the temperature
      regime in the locality and seasonal cycles of maturation of its intermediate
      hosts.

PMID- 7622793
TI  - Structural and functional comparison of trematode haemoglobins.
AB  - Haemoglobins from three different species of trematodes (Gastrothylax crumenifer,
      Paramphistomum epiclitum and Isoparorchis hypselobagri) and their respective
      hosts were digested with papain. Peptides so produced were separated on 10-15%
      SDS-PAGGE. The probability of coincidence of the peptides was analysed
      statistically. Oxygen affinity curves of trematode haemoglobins were found to be
      a rectangular hyperbolic. The Hill coefficient values of all the trematode
      haemoglobins were found to be 1. The P50 values, at 25 degrees C in 0.2M
      phosphate buffer pH 7.4, ranged from 0.8 to 1.6 mmHg.

PMID- 7622794
TI  - Biology of Crassicutis cichlasomae, a parasite of cichlid fishes in Mexico and
      Central America.
AB  - Field study on the biology of Crassicutis cichlasomae Manter, 1936 (Digenea:
      Homalometridae) was carried out in a small swamp in a limestone factory near
      Merida, Yucatan, Mexico. Aquatic snails, Littorina (Littoridinopis) angulifera,
      harbouring C. cichlasomae rediae, cercariae and metacercariae, served both as the
      first and second intermediate hosts. Feeding experiments confirmed the
      conspecificity of metacercariae from naturally infected snails with adults from
      naturally infected fish. Gravid C. cichlasomae worms were obtained from
      experimentally infected fish 19 days post exposure at 22-24 degrees C.
      Examination of fish from the swamp in Mitza and other localities in the Yucatan
      Peninsula showed that the cichlids Cichlasoma urophthalmus and C. meeki were
      definitive hosts of C. cichlasomae. There was no pronounced preference of C.
      cichlasomae adults for the site of their location in the intestine of the
      definitive host; a slightly higher proportion (41%) of worms was only found in
      the anterior third of the gut. The time of miracidium development varied from
      18.5 to 27.5 days; different temperature (20.1-35.7 degrees C) or light/darkness
      regimes influenced only slightly the rate of embryonic development, with shorter
      development times at higher temperature (34.8-35.7 degrees C) and constant
      darkness and/or light. With the exception of the sporocyst, all developmental
      stages are described and figured.

PMID- 7622795
TI  - Development of the free-living stages of Hyostrongylus rubidus and
      Oesophagostomum spp. at different temperatures and humidities.
AB  - Faeces containing a mixture of Hyostrongylus rubidus and Oesophagostomum spp.
      eggs were mixed with vermiculite and water and set up at combinations of
      different relative humidities (65.5%, 79.5% 90.0%, and 100%) and temperatures (5
      degrees C, 10 degrees C, 15 degrees C, 20 degrees C, and 25 degrees C) in order
      to study the rate of egg hatching and larval development. The study established
      that the development from egg to infective larva showed similar patterns for the
      two parasites. Optimum development and survival was in the temperature range from
      15 degrees C to 20 degrees C and at humidities from 79.5 to 95.5%.

PMID- 7622796
TI  - Separation of outer cysts from metacercariae of Fasciola gigantica in an aqueous
      two-phase system.
AB  - The outer cysts (Oc) of Fasciola gigantica metacercariae (Mc) were separated in
      an aqueous two-phase system composed of polyethylene glycol and dextran in
      distilled water. A large number of separated Mc without Oc were recovered in the
      bottom layer rich in dextran in the system. Ten separated Mc in the layer were
      used to inoculate the mouse with a syringe and juveniles were recovered from the
      animals on the 14th day. When the number of juveniles recovered was compared with
      that from the mice infected orally with the same number of Mc, there was a
      significant difference between them (P < 0.05). The former method is easier than
      the latter for inoculation.

PMID- 7622797
TI  - Isolation of microfilariae and eggs of Setaria digitata.
AB  - A simple procedure of gel-filtration was used to purify microfilariae of the
      cattle parasite, Setaria digitata from its eggs. The eggs of S. digitata were
      also isolated from the female worms by picking out the uterine canal. Gel
      filtration gave a recovery of 70% for microfilariae.

PMID- 7622798
TI  - The minimum effective dose of praziquantel in treatment of Hymenolepis diminuta
      in rats.
AB  - To determine the minimum effective dose of praziquantel against Hymenolepis
      diminuta in rats, 5.0 mg/kg, 2.5 mg/kg, 1.0 mg/kg, 0.5 mg/kg, 0.1 mg/kg, or 0.05
      mg/kg praziquantel were given to each of five experimentally infected rats in six
      groups. Faecal samples from each rat were examined on ten consecutive days
      following treatment. The rats were killed and examined for worms on day 10. Based
      on the results of faecal examination and autopsy, the minimum effective dose of
      praziquantel against Hymenolepis diminuta in rats was determined to be 0.5 mg/kg.

PMID- 7622799
TI  - The effects of the presence and absence of intestinal contents on survival, size
      and distribution of Echinostoma caproni in ICR mice.
AB  - Fifteen female ICR mice, 6-8 weeks old, were each exposed to 25 metacercarial
      cysts of Echinostoma caproni. To determine the effects of withholding food on
      survival, size and distribution of E. caproni in ICR mice, two groups of five
      each were maintained without food for 1 day (group A) or 2 days (group B) prior
      to necropsy. Group C consisted of five mice maintained with food for the duration
      of the experiment. All mice were necropsied at 12 days postinfection. There was
      no significant difference in worm survival, body area or distribution between
      group A and C or group B and C mice. The results of this experiment show that
      short-duration removal of food has no effect on worm survival, size or
      distribution of E. caproni adults in the small intestine of the ICR mouse.

PMID- 7622800
TI  - Meta-analysis of pharmacotherapy trials for obsessive-compulsive disorder.
AB  - Since the discovery that clomipramine was effective in the treatment of obsessive
      compulsive disorder (OCD), trials of several different medications for OCD have
      been published. The question of which agent, if any, is the medication of choice
      in OCD is of real clinical concern. Published clinical trials were collected
      using computerized search on MedLine and PsychLit. Trials that met predetermined
      criteria were included in a meta-analysis. Analyses of variance were used to
      compare the specific effect sizes of different medications in OCD. In placebo
      controlled trials, serotonin reuptake inhibitor (SRI) type had a significant
      effect on medication effect size, with clomipramine more effective than
      fluoxetine. Although this finding did not alter when trials were restricted to
      those with large numbers of subjects (n > 50), the analysis was based on a very
      limited number of studies. The fact that so few placebo-controlled studies have
      been done in OCD compromises the findings of this meta-analysis. It would be
      premature to extrapolate the results to clinical practice, where clomipramine and
      certain selective SRIs are currently and justifiably used as first-line agents.
      Nevertheless, the current study supports previous work suggesting that increased
      serotonergic specificity is not necessarily correlated with greater efficacy in
      the treatment of OCD. Further head-to-head comparison studies are necessary to
      confirm or refute this preliminary impression.

PMID- 7622801
TI  - Mirtazapine is more effective than trazodone: a double-blind controlled study in
      hospitalized patients with major depression.
AB  - Two hundred hospitalized patients with DSM-III diagnosis of moderate to severe
      major depressive episode were randomized to receive mirtazapine or trazodone for
      6 weeks in a double-blind trial. The dosages were 24-72 mg/day for mirtazapine
      and 150-450 mg/day for trazodone. The improvement on all depression rating scales
      used was generally greater for mirtazapine, with statistically significant
      differences over trazodone in the Hamilton Psychiatric Rating Scale for
      Depression total score and two subscores (the Bech melancholia factor and
      retardation factor), the Brief Psychiatric Rating Scale total score, the General
      Psychiatric Impression Global Assessment Scale, the Beck score and responder
      rates. Mirtazapine was well tolerated, while the trazodone-treated patients
      experienced somnolence more frequently, particularly during the first 2 weeks of
      treatment. Furthermore, postural symptoms were a clinical problem in 6% of the
      trazodone-treated patients. In this trial, mirtazapine showed significant
      clinical advantages over trazodone in terms of overall efficacy and tolerability.

PMID- 7622803
TI  - Structure-antitubercular activity relationship of phenothiazine-type calmodulin
      antagonists.
AB  - Six neuroleptic (antipsychotic) phenothiazine derivatives which are calmodulin
      antagonists were tested for their activity against Mycobacterium tuberculosis
      H37Rv in order to understand their structure-antitubercular activity
      relationship. Out of the six derivatives tested (trifluoperazine, chlorpromazine,
      triflupromazine, thioridazine, acetopromazine and fluphenazine), trifluoperazine
      appears to be a more potent antitubercular drug than others with a minimum
      inhibitory concentration (MIC) of 5 micrograms/ml. Chlorpromazine,
      triflupromazine and thioridazine are also active but less potent and have a
      higher MIC of 20 micrograms/ml. Acetopromazine and fluphenazine could not
      completely inhibit the growth even at a high concentration of 20 micrograms/ml.
      These results indicate that a methylpiperazinylpropyl group attached to the
      nitrogen (position 10) atom and trifluoromethyl group at the second carbon confer
      antitubercular activity to the phenothiazine molecule. It is suggested that
      trifluoperazine or one of its derivatives could be useful as one of the drugs in
      the multi-drug regimen for the treatment of tuberculosis with psychotic problems
      or vice versa.

PMID- 7622802
TI  - Remoxipride versus haloperidol in healthy volunteers: psychometric performance
      and subjective tolerance profiles.
AB  - The aim of the present study was to evaluate the psychometric effects of
      equivalent clinical doses of remoxipride and haloperidol in comparison with
      placebo in healthy volunteers. In a double-blind design, either 3 mg haloperidol,
      150 mg remoxipride, or placebo were administered to 36 healthy male volunteers
      ranging in age from 19 to 39 years. Performance was assessed using time
      estimation, critical flicker fusion, and choice reaction time tasks. In addition,
      self-ratings on subjective well-being were obtained. In healthy subjects, an
      acute dose of 3 mg haloperidol caused more severe alteration in cognitive
      functioning, cortical arousal, and psychomotor performance than a clinically
      equipotent dose of 150 mg remoxipride. Also, self-rating scales showed that
      subjective tolerance of remoxipride was partly superior to haloperidol. In
      general, the results of this study strongly suggest a difference between the
      psychometric profiles of remoxipride and haloperidol. This difference may be
      essential for maintaining a high level of compliance, especially in the long-term
      treatment of psychotic patients.

PMID- 7622804
TI  - Serotonin uptake inhibitors are superior to imipramine and alprazolam in
      alleviating panic attacks: a meta-analysis.
AB  - The etiology and optimum treatment of panic disorder remain unclear. Imipramine
      and alprazolam are reasonably well established treatments. Several reports have
      suggested that serotonin reuptake inhibitors may also be effective for this
      condition. To investigate this issue, 27 published or presented placebo
      controlled, double-blind studies of DSM-III or DSM-III-R panic disorder were
      subjected to meta-analysis. The serotonin reuptake inhibitors included
      paroxetine, fluvoxamine, zimelidine, and clomipramine. The standard treatments
      were imipramine or alprazolam. All three treatments were highly significantly
      superior to placebo in alleviating panic. The serotonin reuptake inhibitors were
      also significantly superior to both imipramine and alprazolam. The superiority of
      the serotonin reuptake inhibitors remained, but was less pronounced, when they
      were compared to the studies which used higher doses of imipramine or alprazolam.
      These findings underscore the importance of serotonin reuptake inhibitors in the
      treatment of panic disorder and indirectly add to the evidence that serotonergic
      abnormalities may have a role in its etiology.

PMID- 7622806
TI  - Social aspects of treatment of depression.
AB  - Epidemiological studies of depression have shown a consistent, clinical syndrome
      across different societies, most of the symptoms being included in DSM-III-R. It
      is an illness associated with considerable impairment of social function, and in
      DSM-IV social or occupational dysfunction is included as a criterion for
      diagnosis. There is also an increased suicide risk which has to be taken into
      account when selecting treatment. Most depression is treated in general practice,
      where treatment has tended to be of short duration. The usefulness of tricyclic
      antidepressants in limited by their toxicity in overdose and their unwanted side
      effects, which lead to the overuse of health care facilities, reduce compliance,
      and have social and quality of life consequences particularly in long-term
      treatment. On these measures the selective serotonin reuptake inhibitors offer a
      preferred choice of treatment in view of their improved safety and tolerability
      profile.

PMID- 7622805
TI  - SSRIs in anxious-agitated depression: a post-hoc analysis of 279 patients.
AB  - A post-hoc analysis of nine controlled antidepressant trials examined the
      intensity of the initial anxiety and agitation of depressed patients improved by
      SSRIs compared with depressed patients improved by norepinephrine (NE) reuptake
      inhibitors, mixed NE/serotonin reuptake inhibitors and placebo. We report that
      SSRI responders were more anxious-agitated than NE reuptake inhibitor responders,
      suggesting a preferential efficacy of SSRIs in agitated depression.

PMID- 7622808
TI  - Selecting the optimum therapeutic dose of serotonin reuptake inhibitors: studies
      with citalopram.
AB  - Establishing the optimum therapeutic dose of a putative antidepressant is
      important to avoid unnecessarily high doses, which may be associated with
      increased frequency of severity of unwanted side effects, or too low a dose which
      may not achieve the best therapeutic effect. Flexible dose regimes that are often
      used in clinical trial programmes may lead to the use of too high a dose because
      of the attribution of response in depression to the higher dose used later in the
      study rather than being identified as a delayed response to a lower dose used
      earlier. Fixed dose studies provide a more reliable view of the dose response
      relationship and, where differences between doses are small, metanalysis of large
      databases may provide a useful tool for the establishing of the minimum
      therapeutic dose. Metanalysis of the placebo controlled results with citalopram
      demonstrated that the dose-response curves based on log odds ratios showed a very
      flat curve across the 20-60 mg range and that 20 mg appeared therefore to be the
      minimum effective dose. There was evidence that in some subgroups of depressed
      patients a better response may be seen with a higher dose. For example in
      patients with severe depression citalopram was effective compared with placebo in
      doses of both 20 mg and 40 mg. However there was a more pronounced therapeutic
      effect with the higher dose. Similar results have been reported with other
      selective serotonin reuptake inhibitors.

PMID- 7622807
TI  - Comparative pharmacokinetics of selective serotonin reuptake inhibitors: a look
      behind the mirror.
AB  - The presently available selective serotonin reuptake inhibitors (SSRIs)
      citalopram, fluoxetine, fluvoxamine, paroxetine and sertraline, despite their
      common mechanism of action, differ in their chemical structure, metabolism and
      pharmacokinetics. From a clinical point of view, it is of relevance that potency
      to inhibit the cytochrome P450 isozyme CYP2D6 gradually decreases from
      paroxetine, fluoxetine, norfluoxetine, desmethylcitalopram, fluvoxamine, and
      sertraline down to citalopram, explaining to a great extent differences in
      pharmacokinetic interactions between the SSRIs and tricyclic antidepressants,
      which are metabolized by this enzyme. Fluvoxamine interacts with these drugs by a
      mechanism involving inhibition of CYP1A2, CYP3A4, and CYP2C19. Except for
      paroxetine, a substrate of CYP2D6, little is known about the enzymes implicated
      in the metabolism of SSRIs. Fluoxetine and citalopram are used as racemic drugs.
      Data on the stereoselectivity of their enantiomers in the inhibition of serotonin
      (5-HT) uptake in the animal brain, also those available on their metabolism and
      kinetics in humans, are presented. It may be concluded that for routine
      therapeutic drug monitoring, the plasma level measurement of the enantiomers of
      citalopram and fluoxetine is probably of little relevance. However, for the study
      of the structure-activity relationship between these drugs and the cerebral 5-HT
      transporter, the stereochemical differences of these enantiomers should be
      considered. In this sense, the enantiomers of these drugs could represent a
      promising tool to increase present knowledge.

PMID- 7622809
TI  - Citalopram in doses of 20-60 mg is effective in depression relapse prevention: a
      placebo-controlled 6 month study.
AB  - The aim of the present study was to determine whether, in patients with
      depression who had responded favourably to the selective serotonin reuptake
      inhibitor citalopram, there was a therapeutic benefit in continuation treatment.
      Three hundred and ninety-one depressive patients were included in an open short
      term citalopram treatment period. Only patients who responded to treatment at 8
      weeks (total score of 12 or less on the MADRS scale) were randomized to the 24
      week double-blind phase. Seventy-four patients were treated with placebo and 152
      with citalopram at the same constant dose to which the patient had responded in
      the first phase. Relapse was defined as a total score of 25 or more on the MADRS
      scale. Twenty-one patients (13.8%) continuing to receive citalopram relapsed
      compared with 18 patients (24.3%) receiving placebo. The log rank test for
      survival data used to test the quality of relapse hazards between the placebo
      group and the citalopram group showed that patients treated with citalopram had a
      significantly lower relapse rate (p = 0.04). The results of this study are in
      general agreement with those of other studies on antidepressants, and support the
      hypothesis that full dose continuation is more effective than placebo in
      preventing relapse of depression.

PMID- 7622810
TI  - Rationalizing antidepressants for elderly people.
AB  - A rational approach to the use of antidepressants in the elderly must consider
      the evidence as to whether such treatment is efficacious (in controlled trials)
      and effective in clinical practice. Effective treatment of depression depends on
      its detection, and the subsequent initiation and continuation of adequate
      treatment. There is considerable evidence for both under-detection and under
      treatment of depression in old age. Choice of antidepressant will be influenced
      by patients' fitness for treatment and by drug side effect profile, with postural
      hypotension and confusion being particular risks associated with tricyclics. The
      advantages of newer antidepressants (simple regimen, starting dose usually
      adequate, good safety profile, fewer contraindications) are likely to be more
      evident clinically than in controlled trials. Full economic evaluation requires
      data on the direct and indirect costs of depression in old age and on costs of
      treatment failure; many of these data are lacking.

PMID- 7622811
TI  - Modelling the cost-effectiveness of the prophylactic use of SSRIs in the
      treatment of depression.
AB  - Major depressive illness is associated with significant costs for both the
      patient and health care systems. Against a background of limited resources,
      clinical efficacy cannot be regarded as the sole requirement in justifying
      innovative therapy. New therapies must establish both clinical and economic
      effectiveness. Even supposing that clinical trials offer the best vehicle for
      demonstrating such characteristics, trial data are not always in a form which
      enables cost-effectiveness to be investigated. There appears to be widespread
      agreement that patients should continue to receive active medication for a period
      of time, following an initial episode of depression. For the purposes of this
      paper, it is taken as axiomatic that such treatment would be based on selective
      serotonin reuptake inhibitors (SSRIs). The costs and consequences of the
      prophylactic use of SSRIs is investigated by simple modelling methods which
      enable several key parameters to be concurrently varied. The model simulates two
      alternative treatment strategies -- a 'watchful waiting' approach in which
      patients are actively treated for depression once it reemerges; a prophylactic in
      which all patients received SSRIs following their initial episode of depression.
      The average cost per symptom-free patient is estimated to be 271 pounds, under
      the first strategy and between 474 pounds and 389 pounds, under the second
      strategy. The results of this modelling exercise indicate that a strategy of
      maintaining patients with a known history of depression for a 12 month period on
      SSRIs, results in an increased number of patients who are symptom-free. Assessing
      the cost-effectiveness of such a strategy rests ultimately with the comparison of
      marginal costs and benefits.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7622812
TI  - Quality of treatment: what do new antidepressants offer?
AB  - The development of new antidepressant drugs has raised many questions concerning
      their benefits, risks and costs relative to older established compounds, the
      tricyclic antidepressants. Nevertheless, it must be borne in mind that all of the
      newer compounds [atypical tricyclics, selective serotonin reuptake inhibitors
      (SSRIs) and reversible inhibitors of monoamine oxidase] are no more effective
      than the tricyclic antidepressants (TCAs). The reasons for this limited efficacy
      are unclear, as are predictors of response. The upshot is the problem of managing
      the refractory depressive and many stratagems have been proposed. Adverse effects
      vary greatly from class to class and to some extent within class. The TCAs affect
      many systems reflecting their multiple binding capabilities; the SSRIs have side
      effects stemming from their actions on central 5-HT mechanisms. By and large,
      SSRIs are somewhat better tolerated than TCAs, but whether this translates into
      better compliance is not known. Rare putative side effects, such as suicidal
      ideation, have received undue attention but further studies are justified. The
      pharmacokinetics of antidepressants are typically complex and routine monitoring
      of plasma drug concentrations is not helpful. The cost of even the most expensive
      antidepressants is but a fraction of the direct costs of unsuccessful treatment,
      let alone the indirect costs.

PMID- 7622813
TI  - Safety and tolerance profile of venlafaxine.
AB  - Venlafaxine has been shown in clinical trials to be safe and well tolerated in
      patients with major depression. Data were pooled from 19 studies in which 2181
      patients were given venlafaxine, 451 were given placebo and 591 were given a
      reference antidepressant (imipramine, trazodone, clomipramine, maprotiline,
      dothiepin or amineptine). Long-term safety was evaluated in 422 patients who were
      given venlafaxine for at least 1 year; as well, a total of 229 elderly patients
      have been treated with venlafaxine, including 66 who were given it for at least 1
      year. The adverse events that occurred during short-term treatment in > or = 10%
      of patients were nausea, headache, insomnia, somnolence, dry mouth, dizziness,
      constipation, asthenia, sweating and nervousness. In comparator-controlled
      trials, the frequency of anticholinergic events with the reference agents was
      approximately twice that with venlafaxine. The safety profile and patient
      acceptability of venlafaxine are comparable to those of third-generation
      antidepressants, and possibly better than those of first-generation agents.

PMID- 7622814
TI  - Rapid onset of action of venlafaxine.
AB  - It is important to evaluate a new antidepressant in terms of its efficacy in
      relation to that of reference agents such as the tricyclics and monoamine oxidase
      inhibitors. Newer antidepressants have not been shown to be more effective than
      the reference agents, either in the proportion of patients in whom they produce a
      therapeutic response or in their speed of onset of antidepressant activity. The
      serotonin-noradrenaline reuptake inhibitor (SNRI) venlafaxine appears to offer
      some advantages in both of these areas. In a number of short-term placebo- and
      comparator-controlled trials, venlafaxine was shown to be as effective as, and in
      some cases more effective than, the reference antidepressants. These findings
      were also substantiated in meta-analyses of both short-term and long-term
      comparator-controlled studies. In terms of its onset of activity, venlafaxine was
      shown to produce statistically significant differences from placebo as early as
      Day 4 in a study in severely depressed in-patients with melancholia and by Week 1
      in a study in out-patients with major depression. A rationale is presented to
      define the clinical relevance of these findings.

PMID- 7622815
TI  - Clinical utility of venlafaxine in comparison with other antidepressants.
AB  - The newer antidepressants have clearly shown themselves to be safer and to have a
      more acceptable side effect profile than the traditional antidepressants. Greater
      patient acceptability has important consequences in relation to efficacy, in that
      compliance is likely to be better in the long term. One of the newest
      antidepressants, the serotonin- noradrenaline reuptake inhibitor venlafaxine, has
      neurobiologic properties that recommend it for clinical use by both the
      psychiatrist and the general practitioner. Controlled studies have confirmed the
      overall utility of this agent in treating a range of depressive subtypes, such as
      moderate depression and severe endogenous depression, with a low risk of serious
      adverse events and an excellent tolerability profile. In addition, venlafaxine
      has shown a dose-response relationship for efficacy, offering the possibility of
      a wide dose range, which may be suitably employed in different clinical
      situations.

PMID- 7622817
TI  - A fresh look at serotonin-related disorders--differentiating between newer and
      older therapies. Papers presented at 2 satellite meetings in Washington DC, USA
      27 June 1994 and Marbella, Spain 18 October 1992.

PMID- 7622816
TI  - Pharmacologic profile and efficacy of venlafaxine.
AB  - Venlafaxine is a structurally novel phenylethylamine agent with antidepressant
      properties. The preclinical profile suggests that it will be as effective as the
      tricyclic antidepressants (TCAs) with few significant effects on the
      neuroreceptors that mediate many of the side effects common with the TCAs.
      Venlafaxine has been studied in more than 2500 patients in clinical trials; its
      efficacy has been evaluated in more than 700 venlafaxine-treated patients in six
      placebo-controlled trials (five in out-patients and one in in-patients). These
      studies used a wide range of doses (25-375 mg/day) and different dose regimens
      (t.i.d. and b.i.d). The results of these studies clearly establish that
      venlafaxine is significantly more effective than placebo. In the two studies that
      used doses of 375 mg/day, a significant difference from placebo was observed on
      the Montgomery- Asberg Depression Rating Scale (MADRS) at the earliest time
      points assessed, after 4 days of treatment in the in-patient study and after 1
      week of treatment in the out-patient study. Venlafaxine also appears to be as
      effective as some reference antidepressants. A positive dose-response effect has
      been demonstrated with doses of up to 375 mg/day, with a minimum effective dose
      of 75 mg/day.

PMID- 7622818
TI  - The behavioural toxicity of the selective serotonin reuptake inhibitors.
AB  - The serotonin reuptake inhibitors (SSRIs) are generally better tolerated than the
      traditional tricyclic antidepressants (TCAs) in the treatment of major
      depression. In particular the SSRIs are relatively free from cognitive and
      psychomotor effects likely to cause behavioural toxicity. Behavioural toxicity is
      studied using a battery of psychometric assessments. This paper discusses the
      effects of the TCAs and SSRIs on two such assessments, choice reaction time (CRT)
      and critical flicker fusion threshold (CFFT). CRT measures psychomotor speed, and
      CFFT assesses the information processing capacity of the CNS. The behavioural
      toxicity associated with the traditional TCAs can lead to an increased accident
      risk, whereas the SSRIs are not associated with such effects. Clinically relevant
      differences in the behavioural toxicity of the SSRIs are highlighted.

PMID- 7622819
TI  - Safety of antidepressants.
AB  - There are a number of criteria that can be used when selecting an antidepressant.
      In particular safety criteria are important, and a distinction can be drawn
      between "safe" and "less safe" antidepressants. The relative safety of different
      antidepressants has been assessed by looking at answers to the questions: how
      safe is the drug in overdose; how dangerous are its side effects at therapeutic
      dose; and does it have any dangerous interactions with other drugs or substances?
      Based on current data it can be said with reasonable confidence that fluvoxamine,
      fluoxetine, paroxetine and moclobemide are "safe" antidepressants, and mianserin
      and trazodone are also "safe" but to a lesser extent (mainly because of
      hypnosedation). In conclusion, "safe" antidepressants should be considered as the
      first choice in the treatment of depression.

PMID- 7622820
TI  - Fluvoxamine and tricyclic antidepressants (TCAs): how do the TCAs compare as
      "new" drugs with established fluvoxamine?
AB  - The tricyclic antidepressants (TCAs) are still considered as first-line treatment
      for depression, despite the availability of the selective serotonin reuptake
      inhibitors (SSRIs). This paper considers the current situation in reverse by
      assuming that only the SSRIs, in particular fluvoxamine, are available and the
      TCAs (amitriptyline, imipramine, clomipramine and dothiepin) are the potential
      "new" drugs. The criteria for an "ideal" antidepressant are discussed and the
      efficacy, safety and cost-effectiveness of these agents are compared.

PMID- 7622821
TI  - Antidepressant efficacy in relation to item analysis and severity of depression:
      a placebo-controlled trial of fluvoxamine versus imipramine.
AB  - In this investigation, the antidepressant efficacy of fluvoxamine and imipramine
      was compared in a randomized, double-blind, placebo-controlled study lasting 4
      weeks; 338 depressed patients were recruited at five North American centres. For
      the efficacy analyses an intent-to-treat sample was defined. The global efficacy
      of the two drugs was assessed by the Hamilton Depression scale (HAM-D) and
      Clinical Global Impression (CGI) scores. Antidepressant activity was also
      assessed using the percentage of responders on the CGI "improvement" scale. In
      addition the time of onset of antidepressant effect was evaluated by weekly
      analysis of individual HAM-D items. The intent-to-treat sample was stratified
      retrospectively according to the severity of the depression (mild, moderate or
      severe). Regarding global efficacy, compared with placebo, only fluvoxamine
      significantly improved the HAM-D total scores at Week 4 (p < 0.05). There was a
      suggestion from individual HAM-D item scores (depressed mood, suicide, psychic
      anxiety) that fluvoxamine had an earlier effect than imipramine. Overall,
      compared with placebo, more HAM-D items were improved by fluvoxamine than
      imipramine. Fluvoxamine but not imipramine was significantly superior to placebo
      in severely depressed patients as shown by improvements in the HAM-D score (p <
      0.01) and the CGI "improvement" score (p < 0.05). Side effect profiles for the
      active agents were typical for their pharmacological category:imipramine was
      associated with anticholinergic effects, particularly dry mouth, and fluvoxamine
      was associated with nausea and vomiting.

PMID- 7622822
TI  - Comparison of compliance between serotonin reuptake inhibitors and tricyclic
      antidepressants: a meta-analysis.
AB  - A meta-analysis of 67 published randomized controlled clinical trials comparing
      selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants
      (TCAs), which measured discontinuation rates for side effects and lack of
      efficacy, was performed. All multiple publications and trials using non-TCA
      comparators were excluded. Ten studies were placebo controlled; these were
      analysed separately. Overall, the difference in withdrawals due to side effects
      of SSRIs and TCAs was -4.5% (p = 0.0004) and that due to lack of efficacy was
      0.1% (p = 0.86). In the placebo-controlled trials the differences between the two
      groups were -7.9% and -0.1% (p = 0.06 and 0.96), respectively. These results
      demonstrate that SSRIs have a significant and clinically important advantage over
      TCAs with respect to tolerability, whereas efficacy is similar. Treatment failure
      due to poor compliance can increase health-care costs: therefore, in selecting an
      antidepressant for the first-line treatment of major depressive disorders, the
      risks, benefits and costs of each type of treatment need to be critically
      evaluated.

PMID- 7622823
TI  - The role of serotonin in depression and anxiety.
AB  - Although many serotonin (5-hydroxytryptamine; 5-HT) receptors have been
      identified, our knowledge of many of the subtypes is limited. However, we do know
      that 5-HT1A agonists are involved in the treatment of certain anxiety disorders,
      that 5-HT1C and 5-HT2 receptor antagonists may be indicated for the treatment of
      generalized anxiety disorder, and that 5-HT1D receptor agonists are used in the
      treatment of migraine. Recent research has identified that various abnormalities
      in serotonergic function are involved in the pathogenesis of depression and
      anxiety, and has facilitated the development of new pharmacological agents with
      great therapeutic potential, for example the selective serotonin reuptake
      inhibitors (SSRIs). These agents appear to be effective in the treatment of many
      anxiety states and may have greater efficacy than other agents in the treatment
      of certain affective disorders. As the central serotonergic system continues to
      be "mapped", newer and more selective drugs are likely to be introduced, thereby
      possibly improving the overall successful management of depression and anxiety
      disorders.

PMID- 7622824
TI  - Biological dissection of anxiety disorders: the clinical role of selective
      serotonin reuptake inhibitors with particular reference to fluvoxamine.
AB  - The selective serotonin reuptake inhibitor (SSRI) fluvoxamine has been used in an
      attempt to understand whether there is a biological distinction among anxiety
      disorders. A comparison of fluvoxamine with the specific noradrenaline reuptake
      inhibitor maprotiline in patients with panic disorder showed fluvoxamine to be a
      potent anti-panic agent, whereas maprotiline had no effect on the frequency of
      panic attacks. This result supported the hypothesis of serotonergic involvement
      in the pathogenesis of panic disorder. In a second study, unlike fluvoxamine, the
      5-HT2A/2C antagonist ritanserin had no effect on the number of panic attacks, or
      phobic avoidance. This suggested that the efficacy of antidepressants in panic
      disorder was not a result of down-regulation of postsynaptic 5-HT2 receptors.
      Most studies suggest that the efficacy of antidepressants in obsessive-compulsive
      disorder (OCD) is not related to their antidepressant or mood-enhancing effects.
      Fluvoxamine has also been shown to reduce general and phobic anxiety in social
      phobia patients. In conclusion, serotonergic systems are implicated in the
      pathophysiology of global anxiety irrespective of the nosological background, and
      SSRIs, exemplified by fluvoxamine, appear to be effective in panic disorder, OCD
      and probably also social phobia.

PMID- 7622825
TI  - Use of selective serotonin reuptake inhibitors and other serotonergic drugs in
      the biological dissection of affective disorders.
AB  - The need to subtype patients with affective disorders on the basis of biological
      characteristics is well recognized, and much of the research in this area has
      focused on the serotonergic system. Biological subtyping can be approached using
      both peripheral and central markers. Peripheral markers include platelet
      serotonin concentrations, the density and affinity of platelet serotonin reuptake
      and platelet 5-HT2 receptors, and plasma serotonin concentrations. Central
      markers include cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA)
      concentrations, and endocrine, psychological and body temperature responses to
      challenge tests with a number of serotonergic drugs. More recently, the role of
      selective serotonin reuptake inhibitors (SSRIs) and other serotonergic drugs in
      sleep, and in the control of cardiovascular homeostasis, has been studied. This
      may provide a greater understanding of the mechanisms of serotonin dysregulation
      in affective disorders, and may ultimately improve treatment of these conditions.

PMID- 7622827
TI  - Improvement of the Quality of Life in Schizophrenia. Proceedings of a symposium.
      Copenhagen, September 1994.

PMID- 7622826
TI  - Epidemiological data of patients treated with fluvoxamine: results from a 12 week
      non-comparative multicentre study.
AB  - In an open multicentre study designed to closely reflect the clinical situation,
      315 out-patients diagnosed by their psychiatrist as having depression and/or
      obsessive-compulsive disorder (OCD), and/or panic disorder, were treated for 12
      weeks with fluvoxamine (100-300 mg/day). Twelve weeks of fluvoxamine therapy was
      completed by 229 (73%) patients. Longer illness duration prior to treatment was
      associated with a significantly reduced rate of treatment withdrawal, whereas a
      diagnosis of OCD was predictive of treatment withdrawal. The main reasons
      patients discontinued fluvoxamine therapy were adverse effects experienced before
      Week 8, and clinical improvement thereafter. Age, sex, and diagnosis had no
      predictive value for treatment outcome; however, psychiatric antecedents and
      duration and severity of illness at baseline were significant predictors of
      disease severity at endpoint. Fluvoxamine decreased both the frequency and
      severity of baseline symptoms, with improvement continuing for the duration of
      the study. Nausea was the only symptom to show an initial increase in frequency
      and severity, but this subsided after 4 weeks to levels below baseline frequency
      and severity.

PMID- 7622828
TI  - Is intermittent, early intervention medication an alternative for neuroleptic
      maintenance treatment?
AB  - Neuroleptic maintenance medication is clearly effective for relapse prevention in
      schizophrenia. However, besides benefits for the majority of patients, there are
      also failures and/or risks for some patients (e.g. tardive dyskinesia). Since the
      risk-benefit ratio is often difficult to predict in the individual case, this has
      stimulated the search for modifications and alternatives to maintenance
      treatment. In particular, neuroleptic low-dose treatment strategies compare
      favorably with standard-dose treatment concerning relapse prevention and side
      effects. Alternatively, based on prodromal symptoms preceding a relapse, early
      intervention, intermittent neuroleptic treatment strategies have been developed.
      However, all recently completed controlled 2 year studies have not confirmed this
      strategy to be as effective as maintenance treatment in preventing relapse.
      Therefore, for the majority of patients intermittent treatment cannot be
      recommended.

PMID- 7622829
TI  - Depot neuroleptics in relapse prevention: advantages and disadvantages.
AB  - Non-compliance is a major problem in the treatment of schizophrenic patients, a
      problem which is due to the patient's mental condition, to disturbing side
      effects of the medication, to a defective doctor-patient relationship, and to a
      general scepticism towards chemical treatment of mental symptoms. The major
      advantage of depot administration of neuroleptic drugs is the assurance of
      compliance leading to fewer relapses and rehospitalizations. Depot neuroleptics
      also eliminate bioavailability problems related to absorption and first pass
      metabolism and give a stable plasma concentration. Finally, depot neuroleptics
      provide a better and safer way to use the lowest effective dose principle thereby
      reducing the frequency of side effects, including the subjectively distressing
      mental side effects such as akathisia, dysphoria and neuroleptic-induced deficit
      syndrome. Disadvantages include delayed disappearance of potentially irreversible
      and unpleasant side effects after discontinuation and, for many patients, a
      feeling of being controlled. Administered in the proper way, with suitable
      information to the patient and relatives, depot neuroleptics improve the quality
      of antipsychotic treatment, reduce relapse frequency, stabilize the therapeutic
      effect and diminish the level of side effects.

PMID- 7622830
TI  - Adverse effects of antipsychotic drugs.
AB  - The side effects of antipsychotic drugs have always been a major concern for
      clinicians and the appreciation of their importance in the treatment of
      schizophrenia has increased steadily over the years. Epidemiological studies as
      well as trials of the prevention and treatment of antipsychotic side effects are
      the consequences of this development. Results of these studies also have
      important implications for improving compliance and quality of life in
      schizophrenic patients. Thus, side effects research has made the treatment of
      schizophrenia not only safer but also more effective. Next to a brief overview of
      some of the more important adverse events and their treatment, we will also
      discuss these effects in the context of compliance, treatment response and the
      influence of anti-EPS drugs.

PMID- 7622831
TI  - Cost-effectiveness studies in the evaluation of mental health services in the
      community: current knowledge and unsolved problems.
AB  - Care in the community has consistently been found to be cheaper, and has often
      been found to be better, for selected patients on demonstration sites. Most cost
      advantages are obtained by shortening or even eliminating the initial period of
      in-patient care. Health economists can compute cost equations which relate
      clinical characteristics of patients to treatment costs incurred later. As old
      long stay patients are discharged, a degree of cost inflation is inevitable for
      both the hospital and the community service. Strong links have been shown both
      between costs and client needs, and costs, and client outcomes. Integrating
      mental health services with primary care has been shown to increase total costs
      of the service, but to decrease costs per treated case. One weakness of CMH
      schemes is that they are vulnerable to sudden cutbacks, so that the shift of
      resource to the community may not actually occur. The evidence about the efficacy
      of case management is conflicting, but day-care can be used as a method of
      shortening initial admission for some patients.

PMID- 7622832
TI  - The need for quality assurance for a better compliance and increased quality of
      life in chronic schizophrenic patients.
AB  - In many places in the world community care facilities for chronic schizophrenic
      patients are insufficient, leading to a series of complications which can even be
      fatal. The lack of facilities contributes to a decrease in patients' compliance.
      The establishing of a good community care programme for the whole disease period
      will also considerably increase the efficacy of relapse prevention and give the
      patient an acceptable quality of life, and hopefully increase the patient's
      compliance. There is urgent need for therapy standards to be assured and
      monitored according to strict evaluation criteria to produce a better interplay
      between the schizophrenic patient and psychiatric staff.

PMID- 7622833
TI  - The content and context of compliance.
AB  - Compliance is adherence to a prescribed and appropriate treatment, not
      necessarily pharmacological. Non-compliance may occur in up to 50% of patients
      with schizophrenia who are prescribed neuroleptics. It may be commoner in young
      people, particularly if male or from certain ethnic minority groups, but
      demographic factors are relatively unimportant. Clinical features such as
      positive symptoms are associated with non-compliance but the strongest clinical
      relationship is with a "dual diagnosis", usually with an associated alcohol
      abuse. Patients' and relatives' beliefs about schizophrenia and about medication
      are of considerable importance in determining compliance, and can be understood
      in terms of the "health belief model". However, a full understanding of non
      compliance must take into account the relationship between patients and doctors
      in the context of the sick role. Several techniques for increasing compliance
      have been described, but they contain common elements--the provision of
      information within the context of a warm and equitable therapeutic relationship,
      preferably maintained over some time, and the use of the relationship to
      encourage and prompt compliance and to establish more productive views of the
      illness and medication. The costs of poor compliance to sufferers and to society
      alike are considerable, and effective ways of improving it are a crucial part of
      good management.

PMID- 7622834
TI  - What is relapse in schizophrenia?
AB  - Relapse can be defined as "the return of a disease after partial recovery". This
      definition is directly applicable to schizophrenic disorder. Relapse in this
      condition can be evaluated at the symptomatic, phenomenological and behavioural
      levels. Relapse impinges on inter-personal, social and occupational spheres of
      the patient's activity. In turn, relapse has wider implications for the family in
      general, for the provision of medical and social facilities and for health
      economics. There are no generally accepted criteria for relapse but outcomes such
      as violence or suicide, extreme psychotic behaviour and rehospitalization have
      been used. Less obvious criteria include major and minor symptom worsening and
      prodromata. Relapse is a relative term and must take into account the following
      factors: the patient's condition before the original onset of illness; his level
      of functioning before the present episode; the severity of the relapse in terms
      of symptom severity, duration and interference with personal functioning; the
      appearance of any new symptoms or behaviour patterns; the type of treatment given
      prior to relapse, and hence relatively ineffective; the type of treatment given
      during relapse, and its efficacy. Relapses often follow a pattern which may be
      fairly specific to each individual patient. Social factors may have predictive
      power but these need validation in different samples.

PMID- 7622835
TI  - Basic elements in biobehavioral treatment and rehabilitation of schizophrenia.
AB  - The psychopathology and associated disabilities experienced by persons with
      schizophrenia have only partially responded to conventional pharmacological and
      psychosocial treatment approaches. Biobehavioral therapy employs behavioral and
      symptomatic assessment, social learning principles, and skills training, to
      amplify the effects of pharmacotherapy. Comprehensive, continuous, and integrated
      biobehavioral therapy--aiming at early detection and treatment of schizophrenic
      symptoms, family and social skills training, and teaching coping and illness self
      management skills--has been documented to improve the course and outcome of
      schizophrenia as measured by symptom recurrence, social functioning, and quality
      of life. Biobehavioral therapies must be delivered in the context of a
      collaborative relationship among patients, families and clinicians that together
      can optimize outcomes. Services need to be provided by assertive, outreach,
      community-based teams that tailor the type, frequency and scope of services to
      the phase of the individual's illness.

PMID- 7622836
TI  - Psychoeducation and relapse prevention.
AB  - This paper reviews the rationale underlying psychoeducational programs designed
      to prevent or delay relapse in persons with schizophrenia. Since most of these
      programs have been oriented toward patients and their close relatives, the
      studies reviewed have tested the effect of these programs when added to
      maintenance pharmacotherapy. The results of the first generation of studies
      carried out in the late 1970s and 1980s confirmed the positive effects of a
      family-based psychoeducational program on delaying the recurrence of a
      schizophrenic episode. More recent studies, termed the second generation, have
      built on these findings to test more specific hypotheses concerning the most
      efficient format for delivery of such programs (relatives-only groups, single
      family-unit therapy, multiple-family groups). No clear advantage has been found
      for any one format, suggesting that intensive family involvement in the community
      care of schizophrenic, and other psychotic patients as well, may be a critical
      ingredient in successful relapse prevention programs.

PMID- 7622837
TI  - New diagnostic vistas.
AB  - There are many difficulties in establishing criteria for better drug compliance
      and improved quality assurance in the treatment of schizophrenic patients. The
      most serious problem (especially with first episodes) is that of diagnosis. Since
      no biological markers for schizophrenia have been found the clinician is referred
      to "symptom collecting"--including collecting social data. In spite of many
      attempts there is still no general agreement of the concept of schizophrenia.
      This deplorable fact is reflected in the everchanging subdivisions of the
      schizophrenias over the decades: from a division of acute and chronic dementia
      praecox via a classification of simple, hebephrenic, catatonic, paranoid forms,
      on to new classifications based on positive/negative manifestations, divisions of
      type I/type II forms etc. The many different rating scales are reflections of the
      same problem, as are the different diagnostic systems (e.g. DSM-III and ICD-10).
      The recent attempts to make a synthesis of these systems seem promising but raise
      new problems related to etiological and pathogenetic views of psychiatric
      disorders.

PMID- 7622838
TI  - From compliance to collaboration in the treatment of schizophrenia.

PMID- 7622840
TI  - Immunocytochemical investigation of insulin secretion by pancreatic beta-cells in
      control and diabetic Psammomys obesus.
AB  - Hyperproinsulinemia is a characteristic feature of non-insulin-dependent diabetes
      mellitus (NIDDM) caused by pancreatic beta-cell dysfunction through a secretion
      related alteration or impaired proinsulin processing. We have investigated the
      insulin processing and secretion in Psammomys obesus fed with low- and high
      energy diets, which represent a model for diet-induced NIDDM. With a high-energy
      diet the animals develop hyperglycemia and hyperinsulinemia, whereas those
      maintained on a low-energy diet remain normoglycemic. Although a large amount of
      insulin immunoreactivity was detected in beta-cells of the normoglycemic compared
      to hyperglycemic animals, in situ hybridization for insulin mRNA demonstrated a
      particularly high signal in the beta-cells of the hyperglycemic animals. By
      electron microscopy, the beta-cells of normoglycemic animals displayed large
      accumulations of secretory granules, whereas those of the hyperglycemic animals
      contained very few granules and large deposits of glycogen. These results reflect
      a secretory resting condition for the cells of the normoglycemic animals in
      contrast to stimulated synthetic and secretory activities in the cells of the
      hyperglycemic ones. Using colloidal gold immunocytochemistry at the electron
      microscopic level, we have examined subcellular proinsulin processing in relation
      to the convertases PC1 and PC2. Immunolabeling of proinsulin, insulin, C-peptide,
      PC1, and PC2 in different cell compartments involved in beta-cell secretion were
      evaluated. Both PC1 and PC2 antigenic sites were detected in beta-cells of
      hyperglycemic Psammomys, but their labeling intensity was weak compared to the
      cells of normoglycemic animals. In both groups of animals, higher levels of PC2
      were found in the Golgi apparatus than in the immature granules. Major decreases
      in proinsulin, insulin, PC1, and PC2 immunoreactivity were recorded in beta-cells
      of the hyperglycemic Psammomys. In addition, all these antigenic sites were
      detected in lysosome-like structures, revealing a major degradation process.
      These results suggest that the insulin-secreting cells in hyperglycemic Psammomys
      obesus are in a chronic secretory state during which impaired processing of
      proinsulin appears to take place.

PMID- 7622839
TI  - Expression and localization of mRNA for the 16 KD subunit of V-ATPase in the rat
      embryo.
AB  - Vacuolar H(+)-ATPase (V-ATPase), an enzyme composed of multisubunits, is located
      in the membrane of intracellular organelles (e.g., lysosomes, and endosomes) and
      maintains the intraorganellar acidic pH by pumping protons across the membrane.
      Although there is growing evidence for some important role of V-ATPase in cell
      proliferation and differentiation, the functional significance of V-ATPase in
      vivo during mammalian development remains obscure. In the present study we
      investigated the expression and localization of mRNA for the 16 KD subunit of V
      ATPase, an essential sector for enzymatic activity, in prenatal rat by Northern
      blot analysis and in situ hybridization with a specific oligonucleotide probe.
      With Northern blot analysis, consistent expression of the mRNA was observed in
      the embryos throughout the period examined (E14-E20). On in situ hybridization,
      mRNA signal was distributed with various intensities in both the epithelial and
      mesenchymal tissues at embryonic day 14 (E14). In E17 and E20 embryos,
      localization of strong signal became more restricted to distinct mesenchymal
      cells such as fibroblasts adjacent to the epithelia of skin, lung, and intestine,
      the cells of perichondrium, and myoblasts in the process of fusion. These results
      suggest that V-ATPase performs specific functions during the later stages of
      embryogenesis, especially at sites of mesenchymal differentiation and epithelium
      mesenchyme interaction.

PMID- 7622841
TI  - Renal tubule Na,K-ATPase polarity in different animal models of polycystic kidney
      disease.
AB  - Apical mislocation of the ubiquitous transport enzyme Na,K-ATPase has been
      implicated as a feature of cyst development in in vitro studies of human
      polycystic kidney disease (PKD) epithelia. We undertook an immunohistochemical
      study of murine glucocorticoid-induced PKD, the pcy mouse, the cpk mouse, and the
      diphenylthiazole (DPT)-induced rat models of PKD to determine if this feature was
      common to these models of cyst development. Distribution of Na,K-ATPase was
      determined with a polyclonal anti-Na,K-ATPase antibody and a nickel-silver
      enhanced peroxidase color development system. Results were documented objectively
      with densitometric techniques. Control animals appropriate to the age, strain,
      and species of the experimental groups demonstrated the expected polar
      distribution of Na,K-ATPase to the basolateral surface. This distribution was
      more marked in mature animals. Tubular dilatation and cystic change, however,
      were associated with increased apical Na,K-ATPase in all models. The murine
      models demonstrated decreased basolateral staining for Na,K-ATPase compared with
      controls, although this was not a feature of the DPT rat model. Abnormal location
      of Na,K-ATPase is a shared feature of a variety of animal models and human PKD.
      This may contribute to abnormal fluid and electrolyte flux favoring cyst
      formation or may represent expression of a less differentiated renal tubule
      epithelial phenotype.

PMID- 7622842
TI  - Distribution of SPARC in normal and neoplastic human tissue.
AB  - SPARC (Secreted Protein, Acidic and Rich in Cysteine)/osteonectin is a secreted
      glycoprotein that exhibits restricted expression in murine adult and embryonic
      tissues and is associated with cell migration, matrix mineralization, steroid
      hormone production, cell cycle regulation, and angiogenesis. We produced a
      monoclonal antibody, MAb SSP2, against a Ca(2+)-binding region of SPARC and
      evaluated the immunoreactivity of normal and malignant tissue from 118 human
      samples. In normal tissue we found restricted and moderate reactivity with SSP2
      in steroidogenic cells, chondrocytes, placental trophoblasts, vascular smooth
      muscle cells, and endothelial cells. Strong reactivity was found in fibrocytes
      and endothelial cells involved in tissue repair and in invasive malignant tumors,
      including those of the gastrointestinal tract, breast, lung, kidney, adrenal
      cortex, ovary, and brain. We conclude that SSP2 is a useful reagent for detection
      of SPARC in human tissue. Given the broad reactivity of malignant tissues, we
      propose that SPARC expression might contribute to some aspects of tumor
      progression.

PMID- 7622843
TI  - Electron microscopic location of mRNA in the rat kidney: improved post-embedding
      in situ hybridization.
AB  - We determined the optimal technical conditions for post-embedding non-radioactive
      in situ hybridization applied to ultrastructural location of collagen I mRNA in
      rat kidney. The signal-to-noise ratio was improved by enhancing hybridization
      efficiency and distinguishing nonspecific labeling. Probes were labeled with
      digoxigenin or biotin and detected after hybridization by immunogold or
      peroxidase techniques. Under these conditions, the signal was located in
      fibroblasts. With digoxigenin, clusters of gold particles were observed on the
      endoplasmic reticulum (ER) or scattered throughout the cytoplasmic matrix and
      nuclei. With the enzymatic method, diaminobenzidine deposits were found on the ER
      but endogeneous peroxidase partly interfered with the results. Gold particles
      were less numerous in fibroblast cytoplasm with biotin than with digoxigenin.
      Moreover, gold particles condensed on fibroblast and tubular cell mitochondria
      when biotin was used, a phenomenon shown to be due to endogenous biotin by means
      of a histochemical method. The digoxigenin-immunogold system appeared to be the
      best method. The biotin system was subject to limitations such as interference
      from endogenous biotin and poor sensitivity, and mRNA localization was more
      precise and reliable by the immunogold method than by the enzymatic method.

PMID- 7622844
TI  - Enhanced sensitivity for light and electron microscopic in situ hybridization
      with multiple simultaneous non-radioactive oligodeoxynucleotide probes.
AB  - Although oligonucleotide probes are useful for in situ hybridization, their low
      sensitivity compared to riboprobes and cDNA remains a problem. We have
      systematically examined the protocols to provide a general procedure that
      increases the sensitivity of oligoprobes for light and electron in situ
      hybridizations by using mixtures of multiple non-overlapping oligonucleotides
      (multi-oligoprobes). The protocol achieves these improvements with both
      radioactive and non-radioactive oligoprobes. With 33P-labeled probes in a
      semiquantitative assay, we found that mixtures of up to six vasopressin-directed
      multi-oligoprobes, each employed at saturating concentration, led to an additive
      signal with no significant increase of the background. Using this approach with
      non-radioactive oligoprobes, we were able to detect in the hypothalamus several
      low or moderately abundant mRNAs, such as vasopressin heterogeneous nuclear RNA
      and the galanin, dynorphin, and tyrosine hydroxylase mRNAs. Moreover, we showed
      that multi-oligoprobes used in a pre-embedding procedure were suitable for
      studying the ultrastructural compartmentalization of moderately abundant mRNAs.
      Finally, with the same basic approach we demonstrated that two sets of multi
      oligoprobes can be combined for simultaneous detection of two different mRNAs
      using fluorescent dyes, making this approach suitable for high-resolution
      confocal analyses. Overall, our data demonstrate that multi-oligoprobes provide a
      sensitive tool of choice for various applications in which both well-preserved
      morphology and high sensitivity are needed. In particular, these probes appear
      ideal for study of the comparative subcellular localization of mRNAs at both the
      light and the electron microscopic level.

PMID- 7622846
TI  - Bibliography of the current world literature in hypertension.

PMID- 7622845
TI  - Co-localization of manganese superoxide dismutase and NADH diaphorase.
AB  - Manganese superoxide dismutase (Mn SOD), mitochondrial enzyme, defends against
      the toxic effects of superoxide radical (O2.-) in pathological processes by
      catalyzing the conversion of O2.- to hydrogen peroxide (H2O2). The activity of
      another enzyme, NADH diaphorase, forms the basis for a histochemical method used
      commonly to demonstrate nerve cell bodies in the enteric plexuses. We found
      identical patterns of localization of Mn SOD immunoreactivity and NADH diaphorase
      activity in brain, esophagus, stomach, colon, liver, and kidney. NADH diaphorase
      enzymatic activity co-migrated with complexes of Mn SOD on a non-denaturing gel.
      This suggests that the NADH diaphorase may in some way be related to Mn SOD.

PMID- 7622848
TI  - Blood pressure in males and females.

PMID- 7622847
TI  - Trough: peak ratio: clinically useful or practically irrelevant?

PMID- 7622849
TI  - Elevated blood pressure during the first two hours of ambulatory blood pressure
      monitoring: a study comparing consecutive twenty-four-hour monitoring periods.
AB  - OBJECTIVE AND DESIGN: Ambulatory blood pressure monitoring is being used
      increasingly in clinical practice and hypertension research. We have noted
      elevated blood pressure during the initial hours of monitoring. The objective of
      the present study was to examine the consistency, magnitude and duration of this
      elevation, and to determine whether this effect causes significant differences in
      the mean ambulatory blood pressure monitoring values comparing the first (day 1)
      and second (day 2) consecutive 24-h periods of monitoring. METHODS: Fifty
      patients who were hypertensive based on repeated clinic readings were studied
      prospectively. Each underwent continuous 48-h ambulatory blood pressure
      monitoring with a SpaceLabs 90207 monitor. The device recorded blood pressure at
      15-min intervals during the daytime (0600-2159 h) and at 30-min intervals at
      night-time (2200-0559 h). From these readings hourly means were calculated.
      Repeated-measures analysis of variance was performed to compare the hourly means
      of days 1 and 2. RESULTS: Repeated-measures analysis of variance indicated that a
      significant difference existed for both systolic and diastolic blood pressure
      between day 1 and day 2. Paired Student's t-test revealed that this difference
      occurred during the first 2 h of monitoring. The daytime blood pressure was
      higher on day 1 as a result of the initial elevation of blood pressure at the
      onset of monitoring. The initial elevation of blood pressure was present both in
      white-coat hypertensives and in essential hypertensives. CONCLUSION: The first 2
      h of ambulatory blood pressure monitoring are associated with elevated blood
      pressure both in white-coat hypertensives and in essential hypertensives. This
      has a minor effect on mean daytime and 24-h ambulatory blood pressures. We
      propose that improved ambulatory blood pressure monitoring recordings would be
      obtained in clinical practice, and more particularly in research applications, if
      26-h ambulatory blood pressure monitoring was carried out, excluding the first 2
      h from the summary analyses.

PMID- 7622850
TI  - The accuracy of automated blood pressure measuring devices in patients with
      controlled atrial fibrillation.
AB  - OBJECTIVE: To determine whether automated blood pressure measuring devices can
      measure blood pressure accurately in patients with atrial fibrillation. DESIGN:
      Comparison of the accuracy of two electronic sphygmomanometers [Takeda UA-751
      (Takeda) and Copal UA-251 (Copal)] and two ambulatory blood pressure monitors
      [Accutracker 1 (Accutracker) and SpaceLabs 90207 (SpaceLabs)] with that of a
      trained observer using a Hawksley random-zero sphygmomanometer (Hawksley), using
      the sequential same-arm technique. SETTING: University teaching hospital: medical
      wards and outpatient department. SUBJECTS: Twenty-eight patients, mean +/- SD age
      72 +/- 9 years, blood pressure range 90-158/40-96 mmHg, in atrial fibrillation
      with a controlled ventricular rate. MAIN OUTCOME MEASURES: The proportion of
      machine readings > 5 mmHg different from the Hawksley reading was compared with
      that obtained by three sequential Hawksley measurements. The variability of each
      measuring method was assessed by determining the SDD for the paired readings from
      each device. RESULTS: Five per cent of Takeda, 5% of Copal, 14% of Accutracker
      and 21% of SpaceLabs readings could not be obtained. Sequential testing with the
      Hawksley resulted in an accuracy at the 5-mmHg level of (systolic/diastolic)
      79/79%, compared with 64/54% (P < 0.05 for diastolic) for the Takeda, 68/75% (NS)
      for the Copal, 50/36% (P < 0.01 for both) for the Accutracker and 50/29% (P <
      0.01 for systolic, P < 0.001 for diastolic) for the SpaceLabs. Intrapatient
      variability, as assessed by SDD, was 8.3/8.6 mmHg for the Hawksley, similar to
      that for the Copal (7.7/7.3 mmHg) but higher for the Takeda (11.2/19.7 mmHg), the
      Accutracker (22.4/26.3 mmHg) and the SpaceLabs (7.5/14.8 mmHg). CONCLUSIONS:
      Accurate measurement of blood pressure with an electronic device is possible in
      patients who have atrial fibrillation; the Copal UA-251 provides a satisfactory
      level of accuracy. However, the marked difference between devices and the limited
      accuracy of the other machines tested here demonstrates the need to ensure that
      such devices are of proven accuracy in this patient group.

PMID- 7622851
TI  - Influence of the renal sympathetic nerves on renal renin and angiotensinogen gene
      expression in spontaneously hypertensive rats during development.
AB  - OBJECTIVE: To investigate the influence of renal sympathetic denervation on renin
      and angiotensinogen gene expression in the kidney during growth and the
      development of hypertension in spontaneously hypertensive rats (SHR). Comparative
      studies were undertaken in age-matched normotensive Wistar rats. DESIGN: Four
      week-old SHR and Wistar rats were subjected to either denervation of the left
      kidney or sham operation. At age 5, 7 or 9 weeks the rats were lightly
      anaesthetized, carotid blood pressure was measured, a blood sample was taken and
      both kidneys were removed. METHOD: Plasma renin activity was measured by
      radioimmunoassay, and renal renin and angiotensinogen messenger RNA (mRNA) levels
      were measured by Northern blot hybridization followed by densitometric analysis.
      RESULTS: In 5- and 7-week-old SHR the renin mRNA level in the left kidney was
      significantly suppressed compared with that in the sham-operated right kidney and
      with the level in 9-week-old SHR. The renal renin mRNA level in sham-operated SHR
      decreased significantly with increasing age, whereas in the Wistar rats the renal
      renin mRNA level did not change at any age and was not affected by renal
      denervation. The renal angiotensinogen mRNA level gradually increased with age in
      both rat strains and was not affected by denervation, but much higher levels were
      attained in the Wistar rats than in the SHR. CONCLUSION: Renal angiotensinogen
      gene expression was depressed in the SHR, with little evidence of neural
      regulation at any age in the SHR or the Wistar rats. However, in the SHR the
      renal sympathetic nerves elevated renal renin gene expression in the
      prehypertensive stage, but their influence decreased as hypertension developed.

PMID- 7622852
TI  - Genetic variation at the angiotensinogen locus in relation to high blood pressure
      and myocardial infarction: the ECTIM Study.
AB  - OBJECTIVES: To study the association between polymorphisms of the angiotensinogen
      (AGT) gene and blood pressure in population-based samples, and to determine
      whether genetic variation at the AGT locus is involved in the susceptibility to
      myocardial infarction. METHODS: The study population comprised 630 cases who
      survived a myocardial infarction, recruited from the World Health Organization
      Monitoring Cardiovascular Diseases registers in Belfast, Lille, Strasbourg and
      Toulouse, and 741 controls drawn from the corresponding populations. The AGT
      polymorphisms investigated were T174M and M235T. High blood pressure was defined
      as diastolic blood pressure > 100 mmHg or the use of antihypertensive medication,
      or both. RESULTS: In the controls the mean +/- SEM frequency of the M174 allele
      was 0.116 +/- 0.008, and that of the T235 allele was 0.401 +/- 0.013. In the
      whole population blood pressure levels and prevalence of high blood pressure did
      not vary according to T174M and M235T genotypes. However, obesity appeared as a
      crucial factor influencing the relationship between high blood pressure and
      T174M. In subjects with body mass index < 26 kg/m2 there was a 2.4-fold increase
      of the prevalence of high blood pressure in carriers of the M174 allele compared
      with in homozygotes for the T174 allele, whereas no association was detected in
      subjects with body mass index > 26 kg/m2. The association between high blood
      pressure and M235T was not significant in either group. The T174M and M235T
      genotype distributions did not differ between survivors of myocardial infarction
      and controls. CONCLUSIONS: These data suggest that the AGT gene could be involved
      in the predisposition to high blood pressure in non-overweight, but not in
      overweight men, possibly reflecting genetically different types of hypertension.
      No significant impact of the AGT locus in the risk of non-fatal myocardial
      infarction was detected.

PMID- 7622854
TI  - The relationship between low-calcium-induced increase in systolic blood pressure
      and vitamin B6.
AB  - OBJECTIVE: To investigate the relationship between the increase in systolic blood
      pressure caused by a low-calcium (0.1%) diet and the vitamin B6 status in the
      rat. METHODS: Male Sprague-Dawley rats fed a vitamin B6-deficient diet did not
      show any change in systolic blood pressure (SBP) for the first 4 weeks
      (prehypertensive phase), but from week 5 there was an increase in SBP lasting
      until week 10 (hypertensive phase). SBP declined to below normal levels in most
      rats from week 12 on the vitamin B6-deficient diet (posthypertensive phase). The
      effect of altering the level of calcium in the diet at different phases of
      vitamin B6 deficiency was studied. In another experiment the effect on the change
      in blood pressure induced by the low-calcium diet of increasing the dietary
      vitamin B6 level to 2.5-, 5- or 10-fold the normal intake was studied. RESULTS:
      Lowering dietary calcium caused a significant increase in SBP in rats on the
      vitamin B6-sufficient diet. This occurred during weeks 3 and 4 on the low-calcium
      diet. Low levels of calcium on the diet potentiated the hypertension induced by
      the vitamin B6-deficient diet when both deficiencies were present from the
      beginning of the experiment. Feeding a low-calcium diet during the hypertensive
      or posthypertensive phase failed to raise the SBP in these rats. Normalizing the
      vitamin B6 status of posthypertensive vitamin B6-deficient rats restored the
      ability of low dietary calcium to increase SBP in these rats. Increasing dietary
      levels of vitamin B6 by itself reduced SBP in normal rats, and attenuated the
      increase in SBP induced by the low-calcium diet. CONCLUSIONS: Dietary vitamin B6
      deficiency and low calcium in the diet seem to share the mechanisms increasing
      SBP.

PMID- 7622853
TI  - Plasma adrenaline responses to long-term modification of blood pressure in
      normotensive rats and hypertensive rats.
AB  - OBJECTIVE: To examine the relationship between plasma adrenaline and
      hypertension. DESIGN: Plasma adrenaline responses to chronic manipulations of
      blood pressure were tested in normotensive and in hypertensive rats. METHODS:
      Hypertension was induced in normotensive Wistar-Kyoto (WKY) rats by
      administration of the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl
      ester (L-NAME), and blood pressure was lowered in stroke-prone spontaneously
      hypertensive rats (SHRSP) by administering hydralazine. Plasma catecholamine
      responses were monitored using blood samples from conscious unrestrained rats
      under resting conditions. RESULTS: Twenty-four hours after starting L-NAME
      treatment, mean arterial pressure was 22 mmHg higher than in control WKY rats.
      Heart rate and plasma noradrenaline were reflexly reduced, but plasma adrenaline
      was unaffected. After 4 weeks of L-NAME treatment mean arterial pressure was 48
      mmHg higher than in untreated rats. At this stage heart rate had returned to
      normal, but plasma noradrenaline was 33% higher and plasma adrenaline was 117%
      higher than in untreated rats. The elevation of plasma adrenaline was confirmed
      in a study of longer duration, in which plasma adrenaline had doubled after 10
      weeks of L-NAME treatment. Conversely, 24 h after hydralazine treatment in SHRSP,
      mean arterial pressure was reduced by 49 mmHg and there was a reflex elevation of
      plasma adrenaline, noradrenaline and heart rate. However, after 19 days of blood
      pressure reduction with hydralazine, plasma noradrenaline and heart rate had
      returned to normal, but plasma adrenaline had fallen to 30% below normal. Most of
      the change in mean arterial pressure observed with either chronic L-NAME or
      hydralazine could be attributed to modulation of neurally mediated
      vasoconstriction, estimated from mean arterial pressure responses to acute
      autonomic blockade. CONCLUSION: Selective changes in plasma adrenaline levels
      were induced by chronic experimental manipulations of blood pressure. This
      implies that the high plasma adrenaline level observed in spontaneously
      hypertensive rats might be a consequence rather than a cause of their
      hypertension.

PMID- 7622855
TI  - Chronic hyperinsulinaemia and hypertension: the role of the sympathetic nervous
      system.
AB  - OBJECTIVE: To determine the implication of the sympathetic nervous system in the
      relationship observed between insulin resistance and hypertension. DESIGN: Rats
      were chronically treated with insulin for 12 days by subcutaneously implanted
      osmotic pumps and given 10% glucose in their drinking water. A separate group of
      rats also received glucose only, and control rats received tap water. RESULTS:
      Physiological hyperinsulinaemia (1.5 and 4.5 mU/kg per min insulin) increased
      mean arterial pressure by approximately 10 mmHg and heart rate by 60 beats/min,
      and supraphysiological insulinaemia (9 mU/kg per min) did not produce additional
      haemodynamic effects. Insulin-treated rats developed insulin resistance, as shown
      by an intravenous glucose-tolerance test. Glucose treatment alone induced
      intermediate haemodynamic and metabolic responses. Plasma noradrenaline levels
      rose slightly in insulin-treated rats and were positively correlated with mean
      arterial pressure but not with insulinaemia, even though insulinaemia was also
      correlated with mean arterial pressure. The reflex sympathetic activation during
      hypotension revealed, in the presence of a noradrenaline uptake antagonist, that
      insulin increases noradrenaline release but also enhances noradrenaline uptake.
      Chronic hyperinsulinaemia did not alter the sympathetic vascular and cardiac
      responses, as assessed by the measurement of the second messengers produced by
      activation of alpha 1- or beta-adrenergic receptor pathways. CONCLUSION: Chronic
      euglycaemic hyperinsulinaemia seems to modify sympathetic activity through
      several mechanisms, and this action could participate in the elevation of blood
      pressure observed in this rat model.

PMID- 7622856
TI  - Media: lumen ratio in human small resistance arteries is related to forearm
      minimal vascular resistance.
AB  - BACKGROUND: For the evaluation in humans of structural alterations in resistance
      arteries, most studies have used an indirect index, the measurement of minimal
      vascular resistance (mean blood pressure divided by maximal postischaemic blood
      flow) in suitable vascular beds. A sensitive and specific micromyographic
      technique was recently made available for the study of human small resistance
      arteries. Whether a correlation really exists between results obtained with the
      two techniques has not yet been investigated. OBJECTIVE: To evaluate both forearm
      minimal vascular resistance and media:lumen ratio of omental or subcutaneous
      small arteries in normotensive subjects and hypertensive patients. DESIGN AND
      METHODS: Thirty-four individuals were included in the study (age range 35-74
      years; 24 hypertensive, 10 normotensive). Twenty-five had elective abdominal
      surgery and nine hypertensive patients had a gluteal biopsy. Omental and
      subcutaneous small arteries were dissected and mounted on a wire micromyograph
      (Mulvany's technique), and media:lumen ratio and media thickness were measured.
      The dose-response curve to noradrenaline was constructed at cumulative
      concentrations from 3 x 10(-9) to 3 x 10(-5) mol/l. Venous occlusion
      plethysmography was used to measure blood flow in the forearm, and minimal
      vascular resistance was calculated from mean blood pressure and postischaemic
      maximal blood flow (13 min ischaemia plus exercise). RESULTS: A statistically
      significant correlation was found between media:lumen ratio and minimal vascular
      resistance (r = 0.74, P < 0.001) as well as between media:lumen ratio and
      systolic (r = 0.44, P < 0.01) and diastolic (r = 0.38, P < 0.05) blood pressures.
      Similar correlations were observed between media thickness and systolic and
      diastolic blood pressures. Small arteries from hypertensive patients had a
      significantly increased reactivity to noradrenaline (by analysis of variance)
      compared with those from normotensive subjects, in terms of wall tension but not
      of active media stress. CONCLUSIONS: The present study demonstrated that the
      media:lumen ratio of small resistance vessels is significantly related to forearm
      minimal vascular resistance, suggesting that direct and indirect evaluations of
      vascular morphology will give similar results.

PMID- 7622857
TI  - Predictors for hypertensive nephropathy: results of a 6-year follow-up study in
      essential hypertension.
AB  - OBJECTIVE AND DESIGN: To identify predictors for the development of early
      hypertensive nephropathy, 88 previously untreated patients with mild-to-moderate
      essential hypertension (World Health Organization stage I or II) were re-examined
      after 6 years of follow-up. According to previous results, protein excretion,
      urinary excretion of N-acetyl-beta-glucosaminidase (NAG), serum NAG concentration
      and glomerular filtration rate (creatinine clearance) may predict the change in
      renal function. RESULTS: Serum creatinine level increased significantly, but none
      of the patients developed serum creatinine of > 1.3 mg/dl. An elevated protein
      excretion between 200 and 500 mg/day at baseline (microproteinuria), urinary NAG
      excretion, serum NAG concentration and blood pressure control during treatment
      were not related to serum creatinine level at follow-up or change in serum
      creatinine level throughout the 6 years of follow-up. In contrast, a high
      creatinine clearance at baseline was related to a marked rise in serum creatinine
      level after 6 years. The patients with a clear-cut increase in serum creatinine
      level of > 0.2 mg/dl (n = 23) were characterized by a significantly higher
      pretreatment blood pressure at the worksite and a significantly greater initial
      creatinine clearance than the patients with no significant change in serum
      creatinine level. In the two groups age, blood pressure level during therapy, and
      the intensity and duration of blood pressure control were not different.
      CONCLUSION: In patients with uncomplicated essential hypertension,
      microproteinuria, NAG parameters and treatment blood pressure level did not
      predict the change in serum creatinine level in the first 6 years of follow-up. A
      high creatinine clearance (suggesting glomerular hyperfiltration) emerged as a
      clinical diagnostic marker of early hypertensive nephropathy.

PMID- 7622858
TI  - Commentary: renin assays: a debate for clinicians, not only for specialists.

PMID- 7622859
TI  - Commentary: plasma renin methodology.

PMID- 7622860
TI  - Prognostic value of ambulatory blood pressure monitoring.

PMID- 7622861
TI  - Antibody to folic acid: increased specificity and sensitivity in ELISA by using
      epsilon-aminocaproic acid modified BSA as the carrier protein.
AB  - For raising high titre and specific antibody to haptens or drugs, epsilon
      aminocaproic acid modified bovine serum albumin (epsilon-ACA-BSA) was prepared
      for use as a carrier protein. Folic acid (FA) was coupled to epsilon-ACA-BSA,
      Imj.BSA and BSA for raising antibodies in rabbits. Enhancement of FA
      immunogenicity with FA-ACA-BSA was observed. Apart from determination of titre by
      indirect ELISA, dose-response behaviour and specificity of these antisera were
      also compared. FA-ACA-BSA antibody showed high sensitivity and specificity. Using
      this antibody, an ELISA method for the determination of FA was developed. The
      study provides a simple approach to raise highly specific and high titre antibody
      against small molecules.

PMID- 7622862
TI  - Biotinylation of interleukin-2 (IL-2) for flow cytometric analysis of IL-2
      receptor expression. Comparison of different methods.
AB  - The main prerequisites for the use of biotinylated ligands to study the
      expression of growth factor receptors on heterogeneous cell populations, such as
      peripheral blood or bone marrow, by flow cytometric methods, are that the
      biotinylated ligand retains its binding ability and that binding of the
      biotinylated ligand to the receptor does not inhibit the subsequent interaction
      of biotin with fluorescently tagged avidin or streptavidin. Using interleukin-2
      (IL-2), we compared the usefulness of various biotinylation reagents, NHS-biotin,
      S-NHS-biotin, S-NHS-LC-biotin, DBB and photobiotin, and developed optimal
      biotinylation conditions for the preparation of biologically active biotin
      labeled IL-2 and the detection of IL-2 receptor expressing cells by flow
      cytometry. As determined by spot blot analysis, biotinylation of IL-2 was most
      efficient at the highest biotin-to-protein (B:P) ratio used. At a B:P ratio of
      100, most of the biological activity of IL-2 was retained when S-NHS-LC-biotin
      was used. In contrast, most of the biological activity of IL-2 samples that were
      labeled with NHS-biotin or photobiotin was lost under these conditions. Biotin
      labeled IL-2 preparations were tested in order to detect IL-2 receptors on IL-2
      dependent CTLL-2 cells by flow cytometry after sequential staining with the
      biotinylated IL-2 and fluorescence tagged streptavidin. A high B:P ratio
      generally resulted in a high specific fluorescence intensity of the cells,
      particularly when S-NHS-LC-biotin was used as the biotinylation reagent. Biotin
      IL-2 could also be used to detect IL-2 receptors expressed by lymphocytes in
      peripheral blood and bone marrow. Comparison of staining of lymphocytes with
      biotinylated IL-2 and an antibody against the IL-2 receptor alpha chain
      demonstrated that only a subset of the cells that showed a strong fluorescence
      signal after staining with biotinylated IL-2 expressed high numbers of the IL-2
      receptor alpha chain. This is in agreement with the expression of functional IL-2
      receptors on resting T cells and NK cells which do not express the alpha chain.
      After stimulation with PHA, virtually all lymphocytes expressed the alpha chain,
      whereas only part of these cells showed a strong fluorescence signal after
      staining with biotin-IL-2, while the rest of the cells had very low numbers of IL
      2 binding sites. Our results demonstrate that, in addition to staining individual
      receptor subunits with antibodies, staining with biotinylated IL-2 is a useful
      indicator of functional IL-2 receptor expression.

PMID- 7622864
TI  - Rapid expression of an anti-human C5 chimeric Fab utilizing a vector that
      replicates in COS and 293 cells.
AB  - Inhibition of complement system activation requires the development of soluble
      nonimmunogenic inhibitors with good tissue penetrating abilities that are
      themselves unable to activate complement. Chimeric mouse/human Fabs capable of
      blocking the activity of complement proteins are likely to fulfill these
      criteria. Several monoclonal antibodies that inhibit the activation of the human
      complement system have recently been developed. To examine the properties of
      chimeric Fab derived from these monoclonal antibodies, we have developed an
      expression system which allows the rapid production of milligram quantities of
      chimeric Fab. Both the chimeric light chain and the chimeric Fd were co-expressed
      from the same vector, pAPEX-3P. This vector contains the SV40 origin of
      replication, which allows the rapid production of chimeric Fab in COS cells for
      preliminary characterization. Additionally, pAPEX-3P contains the Epstein-Barr
      virus origin of replication and a puromycin selectable marker for maintenance as
      a stable episome in human cell lines. A production system consisting of
      transfected 293-EBNA cells cultured in serum free medium followed by protein G
      Sepharose chromatography of the conditioned medium was found to be sufficient for
      the rapid production of purified chimeric Fab. Here we have utilized this
      expression system to demonstrate that an anti-human C5 chimeric Fab was a potent
      inhibitor of complement activation in both in vitro activation assays and an ex
      vivo model of complement-mediated tissue damage.

PMID- 7622863
TI  - Allergen-induced histamine release in rat mast cells transfected with the alpha
      subunits of Fc epsilon RI.
AB  - A rat mast cell histamine assay (RMCHA) has been developed to quantitate the
      biological activity of a recombinant humanized, monoclonal anti-IgE antibody
      (rhuMAbE25). Rat mast cells (RBL 48), transfected with the alpha subunit of the
      high affinity human IgE receptor (Fc epsilon RI), were presensitized for 2 h with
      human plasma containing IgE specific for ragweed and challenged with ragweed
      allergen in the presence of 50% D2O. Histamine release plateaus at 0.1
      micrograms/ml of ragweed. The release of histamine was time, temperature and Ca2+
      dependent. This ragweed-induced histamine release could be inhibited by rhuMAbE25
      in a dose-dependent fashion with an IC50 of 1.19 +/- 0.31 micrograms/ml (n = 25).
      Other humanized MAbs and recombinant human growth factors neither trigger
      histamine release nor inhibit ragweed-induced histamine release. This RMCHA
      correlates well with the human basophil histamine assay (HBHA) (Fei et al., 1994)
      with a correlation coefficient of 0.93 (n = 59, p < 0.0001). Histamine was also
      released when the cells were presensitized with human plasma containing the
      respective allergen-specific IgE and then challenged with standardized mite, D.
      farinae, house dust mix, standardized cat pelt, or Alternaria tenuis. Comparison
      of allergen-induced histamine release showed a good correlation between RMCHA and
      HBHA with a correlation coefficient of 0.69 (n = 37, p = 0.0001). We conclude
      that RMCHA provides a useful tool to confirm allergen-specific IgE in allergic
      patients and can be used to evaluate the biological activity of any anti-IgE
      monoclonal antibody. Moreover, RMCHA provides an unique opportunity to study the
      mechanism of IgE-mediated histamine release in the absence of interfering
      proteins and growth factors normally present in whole blood.

PMID- 7622865
TI  - Monoclonal antibody mediated capsular reactions (Quellung) in Cryptococcus
      neoformans.
AB  - Capsular reactions ('Quellung') visible by light microscopy were observed when
      capsule-binding monoclonal antibody (mAb) was added to Cryptococcus neoformans
      yeast cells. Capsular reactions were observed with capsule-binding IgM, IgG1,
      IgG2a, IgG2b, IgG3 and IgA mAbs. Scanning electron microscopy revealed that mAb
      binding produced a structural change in the fibrillar network of the capsule. The
      occurrence of capsular reactions with mAbs indicate that this phenomenon can be
      produced by the binding of antibody to a single epitope.

PMID- 7622866
TI  - Isolation and characterization of brain microvascular endothelial cells from
      Saimiri monkeys. An in vitro model for sequestration of Plasmodium falciparum
      infected erythrocytes.
AB  - The adhesion of parasitized red blood cells (PRBC) to the endothelium
      (sequestration) may contribute to the pathogenic events in severe human malaria
      caused by P. falciparum. However, the factors involved in the pathophysiology,
      especially cerebral malaria are poorly understood. Previously, we have shown that
      the squirrel monkey Saimiri sciureus is a potential model for human cerebral
      malaria. In this paper we describe five stable clones of endothelial cell lines
      isolated immediately postmortem from different regions of the brain of Saimiri
      monkeys. The endothelial cell characteristics of these clones were confirmed by
      analyzing their ultrastructural aspects by transmission electron microscopy and
      by immunodetection of various endothelial cell markers. The Saimiri brain
      endothelial cell clones (SBEC) varied in their expression of different surface
      molecules. For example, various combinations of receptors involved in P.
      falciparum PRBC adherence such as CD36, ICAM-1 and E-selectin, were expressed at
      baseline values and could be up-regulated by human srTNF-alpha and human srIFN
      gamma. One of the SBEC clones showed a strong cytoadherence for various
      laboratory strains of P. falciparum despite the absence of surface expression of
      any of the known endothelial receptors implicated in PRBC adherence. This finding
      suggests the existence of a new and uncharacterized PRBC binding receptor. The
      use of target organ specific endothelial cell lines expressing a number of
      different potential P. falciparum PRBC cytoadherence receptors, will be a useful
      in vitro system for the evaluation of strategies for the development of vaccine
      and antimalarial drugs to prevent human cerebral malaria.

PMID- 7622867
TI  - An improved assay for antibody dependent cellular cytotoxicity based on time
      resolved fluorometry.
AB  - A new and faster assay for antibody dependent cellular cytotoxicity based on
      release of europium from target cells is described. This has a number of
      important advantages over the traditional assays based on release of chromium-51
      (51Cr). The new method involves labelling of Wein 133 target cells (B cell non
      Hodgkin's lymphoma cells) which express the antigen, CDw52, with the chelate
      europium diethylenetriaminopentaacetic acid (EuDTPA) according to the method of
      Blomberg et al. (1986). Labelled cells are sensitised (coated) with the anti
      lymphocytic monoclonal antibody, Campath-1H. Human peripheral blood mononuclear
      cells are added to mediate lysis of EuDTPA labelled Wein 133 cells by ADCC.
      Release of EuDTPA from lysed cells is determined by mixing supernatants with
      enhancement solution containing 2-naphthoyl trifluoroacetone, 2-NTA, to form a
      highly fluorescent chelate which is measured using time resolved fluorometry.
      Results obtained with the new EuDPTA release assays were comparable to
      traditional assays based on the release of the radioisotope 51Cr. It is
      anticipated that this assay will have a widespread application among laboratories
      performing ADCC assays. The method is non-hazardous and has been used routinely
      for over 2 years to monitor production and purification of Campath-1H.

PMID- 7622868
TI  - A novel assay for apoptosis. Flow cytometric detection of phosphatidylserine
      expression on early apoptotic cells using fluorescein labelled Annexin V.
AB  - In the early stages of apoptosis changes occur at the cell surface, which until
      now have remained difficult to recognize. One of these plasma membrane
      alterations is the translocation of phosphatidylserine (PS) from the inner side
      of the plasma membrane to the outer layer, by which PS becomes exposed at the
      external surface of the cell. Annexin V is a Ca2+ dependent phospholipid-binding
      protein with high affinity for PS. Hence this protein can be used as a sensitive
      probe for PS exposure upon the cell membrane. Translocation of PS to the external
      cell surface is not unique to apoptosis, but occurs also during cell necrosis.
      The difference between these two forms of cell death is that during the initial
      stages of apoptosis the cell membrane remains intact, while at the very moment
      that necrosis occurs the cell membrane looses its integrity and becomes leaky.
      Therefore the measurement of Annexin V binding to the cell surface as indicative
      for apoptosis has to be performed in conjunction with a dye exclusion test to
      establish integrity of the cell membrane. This paper describes the results of
      such an assay, as obtained in cultured HSB-2 cells, rendered apoptotic by
      irradiation and in human lymphocytes, following dexamethasone treatment.
      Untreated and treated cells were evaluated for apoptosis by light microscopy, by
      measuring the amount of hypo-diploid cells using of DNA flow cytometry (FCM) and
      by DNA electrophoresis to establish whether or not DNA fragmentation had
      occurred. Annexin V binding was assessed using bivariate FCM, and cell staining
      was evaluated with fluorescein isothiocyanate (FITC)-labelled Annexin V (green
      fluorescence), simultaneously with dye exclusion of propidium iodide (PI)
      (negative for red fluorescence). The test described, discriminates intact cells
      (FITC-/PI-), apoptotic cells (FITC+/PI-) and necrotic cells (FITC+/PI+). In
      comparison with existing traditional tests the Annexin V assay is sensitive and
      easy to perform. The Annexin V assay offers the possibility of detecting early
      phases of apoptosis before the loss of cell membrane integrity and permits
      measurements of the kinetics of apoptotic death in relation to the cell cycle.
      More extensive FCM will allow discrimination between different cell
      subpopulations, that may or may not be involved in the apoptotic process.

PMID- 7622869
TI  - A simple method based on PCR for detecting the relative mRNA amounts of the four
      mouse IgG subclasses.
AB  - A simple method based on the polymerase chain reaction (PCR) was developed for
      detecting the relative mRNA amounts of the four mouse IgG subclasses in total RNA
      samples and is described in this report. The main features of this method are,
      first, cDNA amplification including VH through the constant region(CH2 domain) of
      each IgG subclass with a set of consensus PCR primers(VH1BACK and 32P-labeled C
      gamma 32), and secondly, cleavage of the amplified DNA fragments with BamHI and
      XhoI endonucleases which act at distinct cleavage sites in the constant region of
      each IgG subclass. The radioactive intensities of the different sized fragments
      separated on polyacrylamide gel were used to show the relative amounts of IgG
      subclasses at the RNA level. This method provides clear detection of each IgG
      subclass using RNA samples from tissues in which Ig-producing cells are rare.

PMID- 7622870
TI  - Direct microtitre plate enzyme immunoassay of folic acid without heat
      denaturation of serum.
AB  - A new and simple method for enzyme immunoassay of folic acid (FA) has been
      developed, which does not require extraction or heat denaturation of serum. FA
      free serum for standards was prepared by a new immunosorbent technique as
      conventional methods were unsuccessful. The detection limit of the assay is 0.05
      ng/ml. Intra- and interassay variabilities ranged between 5-13.3%. Analytical
      recoveries obtained after spiking with different amounts of FA ranged between 93
      110%. We eliminated the interference of endogenous folate binding protein--a
      major problem in direct FA assay by incubating serum samples (or standards) with
      FA-HRP conjugate in antibody coated plates at 50 degrees C. Comparison of our
      data with results obtained by microbiological assay and also by heating samples
      in alkaline buffer showed good correlation.

PMID- 7622872
TI  - Isolation of human blood dendritic cells by discontinuous Nycodenz gradient
      centrifugation.
AB  - The most potent antigen presenting cell present in peripheral blood, lymphoid and
      non-lymphoid tissue is the dendritic cell (DC). The study of human DC has been
      restricted by their low frequency in the tissues and the lack of a truly DC
      specific surface marker to assist in identification and isolation. Standard
      techniques for the isolation of blood DC generally employ a period of in vitro
      culture followed by flotation on dense albumin gradients, or more recently,
      discontinuous gradients of metrizamide. Dense albumin gradients are time
      consuming to prepare, giving low and variable yields of DC. Metrizamide is more
      convenient, although exposure of monocytes to metrizamide can decrease the
      expression of CD14 and alter the accessory cell properties of antigen presenting
      cells. Here we demonstrate that Nycodenz gradient centrifugation of 16 h
      cultured, T lymphocyte depleted, peripheral blood mononuclear cells (PBMC)
      reliably yields a population of low density cells that is highly enriched for DC.
      Most B and residual T lymphocytes are depleted and NK cell numbers are reduced
      two-fold from the interface cell population. The high density pellet fraction
      exhibits very little allostimulatory activity, indicating that few DC pass into
      the pellet. The low density fraction contains a significant population (20 +/- 5
      (SD)%, n = 8) of cells which fail to stain for the lineage markers CD3, CD11b,
      CD14, CD16, CD19 and CD57. Nycodenz exhibits low toxicity, does not alter the
      allostimulatory activity of antigen presenting cells, and is therefore ideal for
      the isolation of cultured DC.

PMID- 7622871
TI  - Optimization of conditions for specific binding of antibody-coated beads to
      cells.
AB  - It has previously been demonstrated that cells can bind antibody-coated beads;
      this effect can be used to enhance the fractionation of cells using magnetic
      fields or by centrifugation on isopycnic, isotonic density gradients. As a
      general rule, the higher the expression of surface antigens the more beads bind
      to cells. However, we have also noted that other factors also affect the number
      of beads found bound to cells. Experiments have been carried out to determine
      what factors affect binding of antibody-coated beads to cells. The optimum
      conditions for binding of antibody-coated beads to MOLT-4 T cells were found to
      be, namely, a 20:1 bead to cell ratio in a 1 ml incubation volume, with
      continuous end-over-end mixing for 1 h at 25 degrees C. Furthermore, the optimum
      centrifugation conditions at which the samples were separated on isopycnic,
      isotonic density gradients were determined as 220 x gmax for 90 min, at 20
      degrees C. The results indicate the preferred conditions that are necessary to
      achieve optimum bead binding by cells and their subsequent fractionation.
      Different antibody-coated beads were examined including Dynabeads M-450, used as
      a known standard. In addition we describe, as a possible alternative to
      Dynabeads, dense polystyrene beads, for the separation of cells on the basis of
      the immunological identity of the surface of cells using density perturbation
      methods.

PMID- 7622873
TI  - New monoclonal antibodies directed against the propart segment of human prorenin
      as a tool for the exploration of prorenin conformation.
AB  - Six monoclonal antibodies (MAbs) directed against human prorenin were produced by
      immunizing BALB/c mice with a peptide corresponding to the sequence (-17 to +9)
      of prorenin. The new MAbs were screened for their ability to first bind to the
      immobilized peptide and then to prorenin previously captured by an anti-total
      renin MAb. The specificity of the MAbs was confirmed by the total lack of binding
      to active renin. Using BIAcore technology, equilibrium affinity constants of the
      MAbs were determined and ranged from 3.2 x 10(8) to 5.7 x 10(9) l/mol.
      Immunoradiometric assays (IRMA) for prorenin were performed using the anti-total
      renin MAb and the anti-prorenin MAbs. The best results were obtained when an anti
      prorenin MAb was immobilized and the anti-total renin MAb was used as tracer in a
      one-step procedure. Moreover, the signal was significantly increased by the
      presence of the renin inhibitor SR 43845 suggesting that the inhibitor-induced
      conformational change of prorenin could be detected by the MAbs.

PMID- 7622874
TI  - Virus burden in long-term survivors of human immunodeficiency virus (HIV)
      infection is a determinant of anti-HIV CD8+ lymphocyte activity.
AB  - Persons infected with human immunodeficiency virus (HIV) for > 8 years were
      studied to delineate virologic and immunologic attributes of long-term survival.
      Whereas those with 300-700 CD4+ cells/microL often had circulating cytotoxic T
      lymphocytes (CTL) against HIV antigens, those with > 1000 CD4+ cells/microL did
      not. The subjects with > 1000 CD4+ cells/microL had low virus burden, low levels
      of Gag-specific CTL precursors, and minimal CD8+ cell activation. Overall,
      elevated levels of CD8+ cells, CD38 antigen expression on CD8+ cells, and anti
      HIV functions were correlated with increased virus burden, provirus load, and HIV
      plasma RNA levels. A factor that suppressed HIV replication was spontaneously
      secreted from CD8+ cells of most subjects but not from those with high CD4+ cell
      counts. CD8+ cell activities, therefore, may reflect chronic viral stimulation of
      the immune system. Long-term survivors with high levels of CD4+ cells maintained
      control of viral replication but lacked the CD8+ cell activities.

PMID- 7622875
TI  - Antibody class and subclass responses to pneumococcal polysaccharides following
      immunization of human immunodeficiency virus-infected patients.
AB  - Antibodies of the IgM class and IgG2 and IgA2 subclasses are prominent in
      responses to pneumococcal polysaccharides (PPS) but may be decreased in human
      immunodeficiency virus (HIV)-infected patients, among whom invasive pneumococcal
      disease is common. After immunization of HIV-infected and -seronegative subjects
      with pneumococcal vaccine, the number of PPS-specific antibody-secreting cells
      (ASC) producing IgM was significantly lower among HIV-infected subjects, whereas
      PPS-specific IgG and IgA ASC were more comparable. The subclass distribution of
      PPS-specific IgG2-producing (approximately 80%) and IgA2-producing (approximately
      50%) ASC and antibodies in serum were similar. However, before immunization, the
      proportions of PPS-specific IgG2 for both serotypes 8 and 14 in baseline sera
      from HIV-infected patients were significantly decreased compared with controls.
      Thus, the response to PPS among HIV-infected patients may be characterized by
      lower levels of specific IgG2 before immunization and prominent defects in IgM
      responses soon after stimulation.

PMID- 7622876
TI  - Lack of association between acyclovir use and survival in patients with advanced
      human immunodeficiency virus disease treated with zidovudine. Zidovudine
      Epidemiology Study Group.
AB  - To evaluate the association between acyclovir use and survival in patients with
      advanced human immunodeficiency virus infection, observational data from 1044
      persons with AIDS or AIDS-related complex (ARC) and < or = 250 CD4 cells/mm3
      following initiation of zidovudine were analyzed. Of these patients, 336 (32%)
      received regular acyclovir (> or = 6 weeks in 2 months). There were no
      differences in mortality data between acyclovir users and nonusers overall or
      when analyzed from 1 year after first use of zidovudine, from time of AIDS in
      those with ARC at enrollment, from patients with AIDS or < 100 CD4 cells/mm3 at
      enrollment, or from patients taking acyclovir for up to 10 months. Acyclovir use
      was associated with increased mortality (relative hazard, 1.28; P = .057)
      independent of herpesvirus infections and of other characteristics associated
      with mortality. In this study, the use of acyclovir at doses for treatment of
      herpes simplex virus infection in combination with zidovudine was not associated
      with prolonged survival.

PMID- 7622877
TI  - Efficacy of antenatal zidovudine in reducing perinatal transmission of human
      immunodeficiency virus type 1. The New York City Perinatal HIV Transmission
      Collaborative Study Group.
AB  - New York City women (321) enrolled during 1986-1993 in an observational cohort
      study were analyzed retrospectively to determine the effectiveness of antenatal
      zidovudine in reducing perinatal transmission of human immunodeficiency virus
      type 1 (HIV-1) in women with various CD4+ lymphocyte counts (< 200, 200-499, >
      499/microL). When CD4+ lymphocyte level was controlled for, women prescribed
      zidovudine during pregnancy were less likely to transmit HIV-1 to their infants
      (adjusted odds ratio, 0.36; 95% confidence interval, 0.14-0.92). There was no
      conclusive evidence that efficacy of zidovudine depended on CD4+ lymphocyte
      level, suggesting that women with severe CD4+ cell depression, who are at highest
      risk of transmitting HIV-1, may also benefit from zidovudine. Antenatal
      zidovudine treatment alone may substantially lower the risk of perinatal HIV-1
      transmission. These data are consistent with the results of AIDS Clinical Trial
      Group protocol 076 and suggest that a substantial portion of zidovudine's
      protective effect may occur when used during the antenatal period.

PMID- 7622878
TI  - Correlation of clinical progression in human immunodeficiency virus-infected
      children with in vitro zidovudine resistance measured by a direct quantitative
      peripheral blood lymphocyte assay.
AB  - A rapid method for determination of zidovudine resistance was developed and
      results were correlated with clinical outcome in human immunodeficiency virus
      (HIV)-infected children. The zidovudine susceptibilities of HIV-1 isolates from
      34 children were determined through a direct quantitative peripheral blood
      lymphocyte assay and compared with results of the AIDS Clinical Trials Group
      resistance assay. Patients' peripheral blood lymphocytes were 5-fold diluted and
      cocultured with donor lymphocytes and varying concentrations of zidovudine.
      Isolates were defined as sensitive if inhibited by < or = 1.0 microM zidovudine
      and resistant at > 1.0 microM. Children (n = 21) with zidovudine-resistant virus
      had greater evidence of disease progression than did those with zidovudine
      sensitive virus (n = 11) as demonstrated by failure to thrive (57% vs. 9%, P =
      .01) and opportunistic infections (48% vs. 0, P = .006). This assay may be useful
      as a screening tool for development of clinically relevant zidovudine resistance.

PMID- 7622880
TI  - Expression of a murine cytomegalovirus early-late protein in "latently" infected
      mice.
AB  - Monoclonal antibodies were isolated from the spleen of a latently infected mouse
      to identify possible antigenic markers for latent murine cytomegalovirus
      infection. One antibody, AM3, was selected for further study. Characterization of
      the antigen recognized by AM3 confirmed that it is the early-late phosphoprotein
      pp50. The antigen was readily detected by immunoautoradiography in the spleens of
      acutely and latently infected mice. Low levels of the AM3/pp50 transcript were
      also detected in latently infected tissues by in situ hybridization. Presence of
      AM3/pp50 mRNA, as well as IE-1 transcripts, was confirmed by reverse
      transcription-polymerase chain reaction in 3 of 5 latently infected spleens. The
      expression of both immediate-early and early-late classes of viral genes suggests
      that persistent infection may be a component of the MCMV life cycle operationally
      defined as latency and that this gene is not specific for latency.

PMID- 7622879
TI  - Human cytomegalovirus immediate early and late transcripts are expressed in all
      major leukocyte populations in vivo.
AB  - Leukocyte populations were purified by fluorescence-activated cell sorter and
      analyzed for human cytomegalovirus (HCMV) DNA and mRNA using polymerase chain
      reaction (PCR) and cDNA PCR, respectively. Twenty-two blood samples from 17
      patients with active HCMV infection were studied. HCMV DNA was detected most
      frequently in granulocytes and monocytes but was also found in CD4+, CD8+, and
      CD19+ lymphocytes. Viral immediate early and late mRNA was found in ficoll
      enriched mononuclear cells and polymorphonuclear leukocytes. In 11 samples from 9
      patients with active HCMV infection, immediate early mRNA was detected in 8
      lymphocyte, 6 monocyte, and 8 granulocyte fractions. Late mRNA was detected in 7
      lymphocyte, 7 monocyte, and 9 granulocyte fractions. The presence of viral late
      mRNA provides strong evidence for infection of these leukocyte populations with
      HCMV in vivo.

PMID- 7622881
TI  - Antiviral effects of plasma and milk proteins: lactoferrin shows potent activity
      against both human immunodeficiency virus and human cytomegalovirus replication
      in vitro.
AB  - Native and chemically derivatized proteins purified from serum and milk were
      assayed in vitro to assess their inhibiting capacity on the cytopathic effect of
      human immunodeficiency virus (HIV)-1 and human cytomegalovirus (HCMV) on MT4
      cells and fibroblasts, respectively. Only native and conformationally intact
      lactoferrin from bovine or human milk, colostrum, or serum could completely block
      HCMV infection (IC50 = 35-100 micrograms/mL). Moreover, native lactoferrin also
      inhibited the HIV-1-induced cytopathic effect (IC50 = 40 micrograms/mL). When
      negatively charged groups were added to lactoferrin by succinylation, there was a
      4-fold stronger antiviral effect on HIV-1, but the antiviral potency for HCMV
      infection was mostly decreased. Lactoferrin likely exerts its effect at the level
      of virus adsorption or penetration (or both), because after HCMV penetrated
      fibroblasts, the ongoing infection could not be further inhibited.

PMID- 7622882
TI  - Respiratory syncytial virus and influenza A infections in the hospitalized
      elderly.
AB  - Respiratory syncytial virus (RSV) infections in the institutionalized elderly
      have been described; however, there is little information on the impact of RSV
      infection on community-dwelling elderly. The purpose of this study was to
      determine the relative numbers of hospitalizations associated with RSV infection
      and compare the clinical manifestations with influenza A infection. Between
      November and April during 1989-1992, persons > or = 65 years old hospitalized
      with acute cardiopulmonary conditions or influenza-like illnesses were evaluated.
      Evaluation included viral culture, RSV antigen detection, and serologic analysis;
      159 (10%) of 1580 had RSV infection and 221 (11%) of 2091 had influenza A. RSV
      and influenza A cases occurred simultaneously throughout the 3 years. Clinical
      manifestations were similar; however, patients with RSV infection were more
      likely to receive therapy for bronchospasm. Death rates were 10% and 6% for RSV
      infection and influenza A, respectively. RSV infection is the cause of serious
      disease in community-dwelling older persons.

PMID- 7622883
TI  - Passive protection against rotavirus-induced diarrhea of mouse pups born to and
      nursed by dams fed Bifidobacterium breve YIT4064.
AB  - Mouse pups born to and nursed by dams fed Bifidobacterium breve YIT4064 and
      immunized orally with rotavirus were more strongly protected against rotavirus
      induced diarrhea than those born to and nursed by dams immunized with rotavirus
      only. The level of antirotavirus IgA in milk of dams fed B. breve YIT4064 and
      immunized orally with rotavirus was significantly higher than that of dams
      immunized with rotavirus only. The antirotavirus IgA level in feces of dams
      immunized orally with rotavirus was also increased by oral administration of B.
      breve YIT4064. These findings demonstrate that oral administration of B. breve
      YIT4064 enhanced antigen-specific IgA antibody in the mammary gland and in the
      intestine. Oral administration of B. breve YIT4064 may enhance antigen-specific
      IgA antibody against various pathogenic antigens taken orally and induce
      protection against infections in various mucosal tissues.

PMID- 7622885
TI  - The clinical and molecular epidemiology of bacteremias at a university hospital
      caused by pneumococci not susceptible to penicillin.
AB  - To determine the epidemiology of bacteremias due to pneumococci not susceptible
      to penicillin (PNSP) at a university hospital, active microbiologic surveillance
      of bacteremias due to PNSP was done for 28 months. Controls were bacteremias
      caused by penicillin-susceptible pneumococci. Antimicrobial susceptibilities for
      alternative antibiotics were determined. Pulsed-field gel electrophoresis (PFGE)
      and serotyping were used as markers of strain identity. Of 113 pneumococcal
      isolates, 14 (13%) were intermediate or resistant to penicillin (MIC > or = 0.1
      microgram/mL). Twelve PNSP were resistant to other drugs: chloramphenicol (5),
      tetracycline (6), trimethoprim-sulfamethoxazole (5), cefotaxime (1), and
      erythromycin (1). Independently significant risk factors associated with PNSP
      bacteremia were sepsis and prior treatment with beta-lactam antibiotics. PFGE
      revealed 10 distinguishable patterns among 12 isolates available for typing. In
      general, PFGE typing correlated with serotyping. It also distinguished some
      isolates of the same serotype. PFGE typing and serotyping suggest that the
      frequency of PNSP in the San Antonio, Texas, area is not due to dissemination of
      a single clonal strain.

PMID- 7622884
TI  - Group B streptococci elicit leukotriene B4 and interleukin-8 from human
      monocytes: neonates exhibit a diminished response.
AB  - Neonatal monocytes have diminished function compared with adult cells. The
      ability to recruit neutrophils through elaboration of chemoattractants has not
      been evaluated in humans. The pattern of chemoattractant release induced by group
      B streptococci (GBS) also is unknown. Adult and cord blood monocytes were
      stimulated with GBS. Supernatants were used as the attractant in blind well
      chambers; migration to neonatal supernatants was diminished. Interleukin-8 (IL-8)
      and leukotriene B4 (LTB4) were released in greater quantities by adult monocytes
      in response to either GBS or lipopolysaccharide. Opsonization of GBS was not
      required for IL-8 release. Adult monocytes released more LTB4 when stimulated
      with unopsonized GBS than with opsonized GBS; the neonate's LTB4 production did
      not increase. IL-8 and LTB4 accounted for the majority of chemoattractant
      activity released in response to GBS. Decreased production of LTB4 and IL-8 may
      contribute to the neonate's poor host response to GBS.

PMID- 7622886
TI  - Correlation between proinflammatory cytokines and antiinflammatory mediators and
      the severity of disease in meningococcal infections.
AB  - Pro- and antiinflammatory cytokines and mediators were measured in 39 patients
      with acute life-threatening meningococcal infections classified into 3 groups: A,
      meningitis without shock (n = 20); B, meningitis with shock (n = 9); and C, shock
      without meningitis (n = 10). The plasma concentrations of proinflammatory
      endotoxin, tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, and IL-8
      and antiinflammatory cytokines and mediators IL-1 receptor antagonist, IL-10, and
      soluble TNF receptors p55 and p75 were strongly associated with this
      classification; the highest concentrations were in group C. IL-4 was not
      measurable. IL-1 beta was increased only in rapidly fatal cases. In addition,
      cerebrospinal fluid (CSF) was analyzed in 21 patients for TNF-alpha and its
      soluble receptors. In CSF, these compounds were mainly increased in group A,
      reflecting an intrathecal compartmentalized cytokine production. It is concluded
      that both pro- and antiinflammatory mediators are simultaneously increased and
      are strongly associated with a classification based on simple clinical
      parameters.

PMID- 7622887
TI  - Chromosomal restriction fragment length polymorphism analysis of Escherichia coli
      strains causing recurrent urinary tract infections in young women.
AB  - To determine whether recurrent, symptomatic urinary tract infections (UTIs) in a
      given individual are due to the same or different strains, 71 Escherichia coli
      strains that caused recurrent UTIs were prospectively collected from 23 infection
      prone young women and studied by chromosomal restriction fragment length
      polymorphism (RFLP) analysis using pulsed-field gel electrophoresis. Thirty-five
      strains from women with first-episode UTIs were also studied. Overall, 30 (68%)
      of 44 recurrent UTIs were caused by a strain previously identified in that
      person. In contrast, 32 of 35 strains from first-episode UTIs had unique RFLP
      profiles. Analysis of a subset of subjects established that the majority of
      recurrent UTIs were due to reinfection, not persistence of the pathogen within
      the urinary tract, and suggested that the colonic flora was the reservoir for
      these reinfecting strains.

PMID- 7622888
TI  - Chancroid epidemiology in New Orleans men.
AB  - Epidemiologic, clinical, and microbiologic data were collected from 299 men with
      nonsyphilitic genital ulcer disease. One hundred eighteen (39%) were culture
      positive for Haemophilus ducreyi, 57 (19%) were culture-positive for herpes
      simplex virus, and 124 (41%) were culture-negative. Patients with chancroid were
      significantly more likely than those with genital herpes to have been frequent
      users of alcohol (44% vs. 23%, P = .006). They were also more likely recently to
      have used cocaine (25% vs. 9%, P = .013), had sex with a prostitute (17% vs. 5%,
      P = .035), traded drugs for sex (16% vs. 2%, P = .005), and had a sex partner who
      used drugs (38% vs. 13%, P = .001). Culture-negative patients were similar to
      chancroid patients with respect to most epidemiologic risk factors. Despite the
      epidemiologic similarities, the clinical features of culture-negative ulcers
      resembled those of culture-proven herpes ulcers more closely than they did those
      of culture-proven chancroid ulcers. These data establish a link between chancroid
      in the United States and the use of crack cocaine.

PMID- 7622889
TI  - Cross-sectional and longitudinal studies of naturally occurring antibodies to
      Pseudomonas aeruginosa in cystic fibrosis indicate absence of antibody-mediated
      protection and decline in opsonic quality after infection.
AB  - Most patients with cystic fibrosis (CF) develop chronic endobronchial infection
      with mucoid Pseudomonas aeruginosa. It has been suggested that opsonic antibodies
      to the mucoid exopolysaccharide of P. aeruginosa protect older CF patients (> 12
      years of age) who have remained free of colonization by this organism. Serum
      antibodies from chronically infected CF patients had greater total complement
      dependent opsonic activity than did those of older noncolonized patients (P <
      .02), but when bound antibody was equalized, opsonic quality was greater for the
      latter group (P < .03). In longitudinal studies, antibody titers to mucoid P.
      aeruginosa rose greatly after initial infection, but opsonic quality declined (P
      = .002). Twenty CF patients who passed age 12 free of P. aeruginosa colonization
      developed chronic P. aeruginosa lung infection at ages 14-35 years. Thus,
      naturally occurring antibodies do not protect CF patients from P. aeruginosa
      infection, and opsonic quality of serum antibodies deteriorates as infection
      becomes established.

PMID- 7622890
TI  - Analysis of Borrelia burgdorferi sequentially isolated from Peromyscus leucopus
      captured at a Lyme disease enzootic site.
AB  - Thirty isolates of Borrelia burgdorferi sequentially cultured from 15 naturally
      infected white-footed mice (Peromyscus leucopus) were examined for variability in
      protein and plasmid profiles. Heterogeneity was detected in OspB and OspC and in
      proteins between 18.0 and 28.0 kDa by PAGE. Plasmid profiles were heterogeneous
      in the first isolate from 11 mice (73%) and between the first and last sequential
      isolate from 13 mice (87%). Comparison of the first and last isolates showed
      increased expression of OspC in 6 mice (40%) and was associated in each case with
      a shift in mobility of a 16.0-kb plasmid, suggesting that regulatory elements of
      ospC may reside on this plasmid. Hybridization studies suggested that individual
      mice may have been infected by a heterogeneous population of spirochetes and that
      changes in the protein and plasmid profiles between the first and last sequential
      isolates from some mice may have been the result of clonal selection.

PMID- 7622891
TI  - Epidemiologic and diagnostic studies of patients with suspected early Lyme
      disease, Missouri, 1990-1993.
AB  - A retrospective case-control study investigated 45 Missouri outpatients with
      annular rashes meeting a surveillance case definition for erythema migrans and
      with onset in 1990-1991. Risk factors included being male, living near a body of
      water, and hunting. Twenty patients (44%) associated their rash with the bite of
      a tick; of these, 5 described an adult Amblyomma americanum. A typical rash was
      described as expanding over time and measuring 8 cm in diameter at 4 days after
      onset. Mild constitutional symptoms were common but fever was uncommon. Serologic
      tests failed to incriminate Borrelia burgdorferi or selected other arthropodborne
      pathogens. Skin specimens from suspected erythema migrans lesions of 23 Missouri
      patients sampled prospectively in 1991-1993 were culture-negative for B.
      burgdorferi. Thus, tick bite-associated annular rashes in Missouri remain
      idiopathic. Possible causes include infection with a novel A. americanum
      transmitted pathogen and an atypical toxic or immunologic reaction to tick
      associated proteins.

PMID- 7622892
TI  - Opsonic activities of surfactant proteins A and D in phagocytosis of gram
      negative bacteria by alveolar macrophages.
AB  - Surfactant proteins A and D (SP-A, SP-D) can interact with lipopolysaccharide
      (LPS) and stimulate alveolar macrophages. The opsonic activities of SP-A and SP-D
      for bacteria with different types of LPS and alveolar macrophages were
      investigated. In flow cytometric studies with fluorescein-labeled rough (J5) and
      smooth (O111) Escherichia coli and rat alveolar macrophages, SP-A enhanced
      binding of J5 but not O111 bacteria to macrophages. Most importantly, SP-A
      enhanced ingestion of J5 bacteria by alveolar macrophages and subsequent
      bacterial killing. Immunoelectron microscopy demonstrated that J5 bacteria, the
      interface between the bacterium and the outer membrane of the alveolar
      macrophage, and ingested bacteria were heavily labeled with SP-A. In contrast, SP
      D did not mediate phagocytosis. SP-A acted as an opsonin in the phagocytosis of
      rough LPS-containing bacteria by alveolar macrophages, emphasizing the possible
      role for SP-A in the alveolar defense system.

PMID- 7622893
TI  - Deferoxamine B but not deferoxamine G1 inhibits cytokine production in murine
      bone marrow macrophages.
AB  - The iron chelator deferoxamine (DFO) B enhances virulence of Yersinia
      enterocolitica and modulates cellular immune responses. Since cytokines mediate
      effector mechanisms in resolution of yersiniae from infected tissues, the impact
      of DFO B and DFO G1 on cytokine production by murine bone marrow macrophages
      (BMM) was investigated. BMM were stimulated with lipopolysaccharide (LPS) of
      Salmonella typhimurium or infected with Y. enterocolitica. DFO B inhibited
      interleukin (IL)-6, IL-12, and tumor necrosis factor (TNF)-alpha mRNA production
      4-fold (shown by semiquantitative reverse transcription polymerase chain
      reaction). TNF-alpha and IL-6 protein production was reduced 50% by DFO B. In
      contrast, DFO G1 had no effect on cytokine production. Moreover, cytokine
      production by Yersinia-infected BMM was decreased by plasmid-encoded Yersinia
      proteins. Thus, plasmid-cured strains induced higher cytokine responses in BMM
      than did the wild type strain. These results suggest that DFO B acts in a bimodal
      fashion in yersiniosis: iron supply to the pathogen and immunosuppression of the
      host.

PMID- 7622894
TI  - Limited persistence in and subsequent elimination of Pneumocystis carinii from
      the lungs after P. carinii pneumonia.
AB  - The purpose of this study was to determine the period of persistence of
      Pneumocystis carinii in the lungs after P. carinii pneumonitis (PCP). After
      primary PCP was induced with dexamethasone, experimental rats were moved to a
      high-efficiency particulate air-filtered isolator to prevent further exposure to
      environmental P. carinii and allowed to recover. At intervals thereafter, sample
      groups were transferred to a second isolator and reimmunosuppressed with
      dexamethasone to provoke PCP if P. carinii were present. Reactivation of PCP was
      assessed by histologic examination, counts of cysts per gram of lung, and DNA
      amplification using nested polymerase chain reaction. A sequential and
      progressive decrease in P. carinii was detected. Thus, P. carinii is cleared from
      the lungs of > or = 75% of animals within 1 year after an episode of PCP,
      implying that persistence of latent organisms is limited.

PMID- 7622895
TI  - Cytoplasts generate oxidants but require added neutrophil granule constituents
      for fungicidal activity against Candida albicans hyphae.
AB  - Killing of Candida albicans hyphae requires oxidant generation by neutrophils
      (PMNL), but it is uncertain whether hyphal killing is mediated by PMNL oxidants
      alone or requires contributions by granule constituents. This was assessed using
      U-cytoplasts (U-CYT), anucleate PMNL fragments depleted of cytoplasmic granules
      but retaining motility and respiratory burst activity. Granule-depleted U-CYT
      killed Staphylococcus aureus, but hyphae remained viable despite targeted
      generation of putatively fungicidal oxidants by avidly adherent U-CYT. Hyphal
      killing occurred by combining U-CYT with sublethal concentrations of purified
      PMNL granule extracts approximating those present in equivalent numbers of intact
      PMNL. Contributions of granule constituents were not entirely attributable to
      purified granule constituents with known antimicrobial activity (lactoferrin,
      cathepsin G, myeloperoxidase, and human neutrophil peptide defensins 1-3)
      individually or combined. Thus, oxidant generation by intact PMNL may be
      necessary but not always sufficient to mediate hyphal killing without
      complementary nonoxidative mechanisms.

PMID- 7622896
TI  - Clearance of circulating filarial antigen as a measure of the macrofilaricidal
      activity of diethylcarbamazine in Wuchereria bancrofti infection.
AB  - Small doses of diethylcarbamazine (DEC) clear microfilariae (MF) from the blood
      of Wuchereria bancrofti-infected persons, but the dose and regimen required to
      kill adult worms is not clearly defined. A prospective study was undertaken to
      examine the macrofilaricidal effect of DEC and the ability of an assay for
      circulating filarial antigen (CFA) to define the effect. Twenty-five MF-positive
      subjects and 7 MF-negative but CFA-positive subjects were treated with DEC and
      followed for 18 months. Of the 25 MF-positive patients, 24 cleared MF, and 22 of
      26 CFA-positive subjects cleared CFA. A significantly greater decrease in
      antifilarial IgG4 was seen in patients who cleared CFA than in those who did not.
      The complete clearance of CFA observed after therapy with DEC indicates that
      assessment of CFA clearance is a useful means for detecting macrofilaricidal
      effects of antifilarial chemotherapy.

PMID- 7622897
TI  - Level of cytomegalovirus (CMV) DNA in cerebrospinal fluid of subjects with AIDS
      and CMV infection of the central nervous system.
AB  - The objective of this study was to correlate cytomegalovirus (CMV) DNA levels in
      the cerebrospinal fluid (CSF) of subjects with AIDS with clinical and pathologic
      findings attributable to CMV infection of the central nervous system (CNS). CMV
      polymerase chain reaction (PCR) was done on serial dilutions of CSF samples from
      24 AIDS patients with autopsy-proven CNS disorders. CMV DNA was detected in CSF
      from 12 of 13 subjects with evidence of CMV infection of the brain or spinal cord
      but in none of 11 subjects without autopsy evidence of CMV CNS infection.
      Subjects whose CSF contained > 10(3) CMV DNA molecules/8 microL of CSF had severe
      CMV CNS disease (e.g., ventriculoencephalitis). PCR appears to be more useful
      than clinical and neuroradiologic findings for documenting CMV infection of the
      CNS in patients with AIDS. Quantitation of CMV DNA in CSF shows promise for
      evaluation of the extent of involvement.

PMID- 7622898
TI  - Mouse cytomegalovirus reactivation in severe combined immune deficient mice after
      implantation of latently infected salivary gland.
AB  - The hypothesis that replication-competent mouse cytomegalovirus (MCMV) is
      detectable in severe combined immunodeficient (scid) mice after implantation of
      latently infected tissue was examined. Sections of latently infected salivary
      gland from 5 BALB/c mice were implanted into 20 C.B-17 scid mice. Recipient scid
      mice were sacrificed weekly for 5 weeks, and MCMV infection was detected in
      target organs using culture and DNA polymerase chain reaction (PCR). All donors
      were negative by standard culture but positive by DNA PCR. Replicating MCMV was
      recovered from 9 of 15 recipient scid mouse salivary gland, lung, liver, or
      spleen samples at postoperative weeks 2-5. No virus was recovered from recipient
      scid mice at weeks 1 or 12. Transplantation of latently infected tissues into
      scid mice resulted in rapid reactivation and dissemination of the virus. Further
      study of this model promises insight into the mechanisms of CMV latency and
      reactivation.

PMID- 7622899
TI  - Squamous epithelial proliferative lesions associated with rhesus Epstein-Barr
      virus in simian immunodeficiency virus-infected rhesus monkeys.
AB  - Proliferative lesions were found on the squamous epithelium of the tongue,
      esophagus, or penis or haired skin of the lip, hand, or thorax of 8 simian
      immunodeficiency virus-infected rhesus monkeys that died of simian AIDS. The
      lesions were focal and consisted of hyperkeratosis, parakeratosis, and acanthosis
      in the skin, with additional ballooning degeneration in the tongue, esophagus,
      and penis. The epithelial surfaces were frequently colonized by Candida species
      or gram-positive cocci. Intranuclear inclusion bodies were seen in cells in the
      middle and superficial layers. Herpesvirus virions were found in inclusion
      bearing cells by transmission electron microscopy. An Epstein-Barr-like virus was
      identified in inclusion-bearing cells by immunohistochemistry and in situ
      hybridization. No virus was detectable in basal layers of the epithelium. These
      lesions resemble oral hairy leukoplakia in AIDS patients and may thus provide a
      useful primate model to study permissive epithelial infection by Epstein-Barr
      like viruses.

PMID- 7622900
TI  - Inhibition of the offspring anti-recombinant gp120 antibody response to a human
      immunodeficiency virus vaccine by maternal immunization in a murine model.
AB  - A murine model was developed for assessing the effects of passively transferred
      polyclonal maternal anti-gp120 antibodies on the subsequent immunization of the
      offspring with recombinant gp120SF2 in complete Freund's adjuvant (rgp120SF2
      CFA). Adult female BALB/c mice were immunized with rgp120SF2-CFA 6 weeks before
      mating. The 3-week-old offspring were subsequently immunized with the same
      vaccine and followed for 9 weeks. Both the total IgG anti-rgp120SF2 and the anti
      V3 IgG antibody response to vaccine were inhibited in the experimental animals.
      The total IgG anti-rgp120SF2 response was < 20% of the control response (P <
      .001) 9 weeks after immunization. Anti-V3 antibody was also decreased. As vaccine
      studies begin in infants, the effects of preexisting antibody on the infant
      response to human immunodeficiency virus vaccines must be considered.

PMID- 7622901
TI  - Testing for antibody to human immunodeficiency virus type 1 in a population in
      which mycobacterial diseases are endemic.
AB  - During a large epidemiologic study in the Karonga District of northern Malawi,
      serum samples from 139 patients with incident leprosy, 124 with newly diagnosed
      leprosy, 277 patients with incident tuberculosis, and 2296 controls were tested
      for antibodies to human immunodeficiency virus. Sera were tested according to a
      four-test protocol using two ELISAs and two particle agglutination assays.
      Overall, 188 samples were considered positive, 2634 were considered negative, and
      14 were indeterminate. All 18 available positive specimens from leprosy patients,
      a random sample of 14 positive specimens from tuberculosis patients, and 15
      positive specimens from controls were tested by Western blot. There was no
      evidence of substantial numbers of ELISA false-positives in any patient group or
      among controls.

PMID- 7622902
TI  - Antiretroviral therapy suppresses the constitutive production of interleukin-1
      associated with human immunodeficiency virus infection.
AB  - Interleukin (IL)-1 is constitutively produced by monocytes of human
      immunodeficiency virus (HIV)-seropositive persons. The changes in the production
      of IL-1 by monocytes of 24 HIV-infected patients were investigated during the
      course of 8 months of antiretroviral therapy. At month 8, the amounts of
      biologically active IL-1 and IL-1 alpha and -beta proteins produced by freshly
      obtained monocytes and by monocytes cultured for 24 h in the absence of
      lipopolysaccharide (LPS) decreased significantly compared with pretreatment
      values or decreased below the limits of detection in the assays. Antiretroviral
      therapy also resulted in enhanced secretion of IL-1 receptor antagonist (IL-1Ra)
      by LPS-stimulated patients' monocytes. The reduction in the constitutive
      production of IL-1 and the increased ability of stimulated cells to produce IL
      1Ra associated with antiretroviral therapy may also be of importance in reducing
      a major pathway of amplification of viral replication in infected monocytes and
      lymphocytes.

PMID- 7622903
TI  - Equal IgG antibody response to pneumococcal vaccination in all stages of human
      immunodeficiency virus disease.
AB  - To evaluate the immunogenicity and safety of a 23-valent pneumococcal vaccine in
      human immunodeficiency virus (HIV)-seropositive patients, 80 men and 18 women
      received 1 dose of the vaccine (Pneumo 23; Pasteur Merieux MSD, Brussels). The
      total IgG antibody response against all 23 Streptococcus pneumoniae capsular
      antigens was measured. Antibody levels were expressed in arbitrary units per
      microliter, referring to a standard curve. Geometric mean titers of the total IgG
      capsular antibodies on the day of vaccination and 30-45 days later were compared.
      The ratios of titers after and before vaccination in patients with > 500, 200
      500, and < 200 CD4 lymphocytes/microL were 10, 10, and 12.6, respectively.
      Nonresponse (ratio < 4) occurred in 17% of patients and was unrelated to CD4 cell
      count. The vaccine was well tolerated; no serious side effects occurred. In 83%
      of the patients with HIV infection, the total antipneumococcal IgG level was
      higher after vaccination.

PMID- 7622904
TI  - Mapping of linear epitopes of the regulatory proteins of human T cell
      lymphotropic virus (HTLV) type II: identification of an HTLV-IIb-restricted
      epitope.
AB  - Epitope mapping analyses using synthetic peptides representing the RexII and
      TaxII proteins identified predominant seroreactivity to the carboxyl terminus of
      the HTLV-IIG12 TaxII protein (G12Tax 22-G12Tax24, amino acids [aa] 312-356).
      Moderate reactivity to only 1 RexII peptide (G12Rex9, aa 121-140) was found,
      while all other RexII and TaxII peptides exhibited minimal reactivity. Peptide
      G12Tax24 (aa 337-356) corresponded to the extended portion of the TaxII protein
      characteristic of HTLV-IIb viruses and appeared to represent an HTLV-IIb
      restricted epitope. This study showed that this peptide can be used in
      immunoassays as a quick, simple serologic tool for assessing the minimal number
      of HTLV-IIb viruses present within specific populations, especially when genomic
      DNA is not available.

PMID- 7622905
TI  - The absence of evidence of staphylococcal toxin involvement in the pathogenesis
      of Kawasaki disease.
AB  - To detect a causative superantigen and to clarify a possible role for
      staphylococci in Kawasaki disease (KD), culture supernatants of individual
      bacterial isolates from 11 acute-stage patients were studied. Toxic shock
      syndrome toxin-1 (TSST-1) and antibody to TSST-1 and enterotoxins A (SEA), B
      (SEB), and C (SEC) in acute (mean, day 7) and late convalescent (mean, month 15)
      sera from 26 patients (12 with coronary artery aneurysms) and 22 age-matched
      controls were measured. Only 1 of 60 supernatants was mitogenic for human
      lymphocytes; it was 1 of the 4 Staphylococcus aureus isolates. Mitogenicity was
      neutralized by sera obtained after administration of intravenous gamma globulin
      (mean, week 4) but not by late convalescent sera. TSST-1 was detectable in 2 of
      26 acute sera and 1 of 22 control sera. No KD but 1 control serum had IgM to TSST
      1. IgG seroconversion rates to TSST-1, SEA, SEB, and SEC were 10%, 15%, 21% and
      16%, respectively. These data do not support the involvement of toxin-producing
      staphylococci in KD.

PMID- 7622906
TI  - Anti-polysaccharide immunoglobulin isotype levels and opsonic activity of
      antisera: relationships with protection against Streptococcus pneumoniae
      infection in mice.
AB  - Relationships between in vitro parameters (opsonic activity and anti-pneumococcal
      polysaccharide [PS] antibody subclasses) and in vivo mouse protection were
      established by logistic regression analysis. Data were from 158 mice challenged
      with pneumococci after vaccination with synthetic oligosaccharide- and PS-protein
      conjugates in combination with the adjuvant Quil A. The hypothesis that serum
      opsonic activity has predictive value for protection against pneumococcal
      infection was tested. Serum opsonic activity was well correlated with protection
      (chi 2 = 35.5, P < 0.001), although a stronger correlation was observed for anti
      PS IgM and IgG. The combined use of IgG and opsonic activity as predictor
      variables yielded the best fitting model for predicting protection (chi 2 = 74.1,
      P < 0.001). When opsonic activity data were added to models that included various
      antibody isotypes, the statistical significance of the models was enhanced. Thus,
      the opsonic activity of antisera induced by pneumococcal vaccines can predict
      mouse protection.

PMID- 7622908
TI  - Cat-scratch disease--Connecticut, 1992-1993.
AB  - A prospective population-based surveillance system was established to
      characterize the epidemiology of cat-scratch disease (CSD) among residents of
      Connecticut who were reported to the state health department with a diagnosis of
      suspected CSD. During 1992 and 1993, 246 persons met the case definition, for an
      average statewide annual incidence of 3.7/100,000 persons. The median age of
      patients with CSD was 14 years (range, 1-64), and 52% were female. The age
      specific attack rate was highest among persons < 10 years of age (9.3/100,000)
      and decreased with increasing age. Symptoms in addition to adenopathy were noted
      by 74% of case-patients. Eleven percent of all case-patients were hospitalized.
      There were no deaths. Most patients with clinically diagnosed CSD developed an
      immunologic response to Bartonella species. Our data suggest that although CSD is
      primarily a disease of younger persons, the age spectrum is wider than was
      commonly appreciated.

PMID- 7622907
TI  - Impact of Streptococcus pneumoniae bacteremia and human immunodeficiency virus
      type 1 on oral mucosal immunity.
AB  - To determine whether defects in mucosal immunity were associated with invasive
      disease caused by a mucosal pathogen, Streptococcus pneumoniae, levels of
      salivary immunoglobulins and nonspecific immune factors were compared in subjects
      with human immunodeficiency virus type 1 (HIV-1) infection and in HIV-1
      seronegative subjects with and without pneumococcal bacteremia. The IgA2 subclass
      may be of particular importance because S. pneumoniae produces IgA1 protease,
      which cleaves IgA1 but not IgA2. Levels (37-56 micrograms/mL) and proportions
      (11%-17%) of IgA2 were similar among groups. Serotype-specific capsular salivary
      IgA was present in a minority of patients with acute bacteremia. Levels of
      lactoferrin were increased with bacteremia. Neither selective mucosal IgA2
      deficiency nor impaired nonspecific upper respiratory mucosal responses were
      associated with invasive pneumococcal disease during HIV-1 infection; thus, other
      defects in mucosal cellular responses and systemic immunity may predispose HIV-1
      infected patients to invasive pneumococcal disease.

PMID- 7622909
TI  - Osteitis caused by bacille Calmette-Guerin vaccination: a retrospective analysis
      of 222 cases.
AB  - To evaluate the frequency, clinical features, and prognosis of patients with
      osteitis caused by bacille Calmette-Guerin (BCG) vaccination, medical records
      from Finnish children based on nationwide registration from 1960 to 1988 were
      retrospectively analyzed. During the study period, three different BCG vaccine
      preparations were used. In 222 children, diagnostic criteria of BCG osteitis were
      fulfilled. The age at onset of BCG osteitis varied from 0.25 to 5.7 years. The
      most common sites of osteitis were metaphyses of the long bones. The lower
      extremity (58%) was affected more often than the upper (14%). Osteitis was
      situated in the sternum in 36 patients (15%) and in the ribs in 27 (11%). The
      frequency of BCG osteitis, but not the clinical parameters, was closely
      associated with the vaccine preparation used. Only 6 children were left with some
      sequelae. With adequate treatment, the prognosis for children vaccinated with BCG
      is good.

PMID- 7622910
TI  - Interleukin-1 contributes to increased concentrations of soluble tumor necrosis
      factor receptor type I in sepsis.
AB  - Studies were done in baboons and humans to assess the role of interleukin (IL)-1
      on the release of soluble tumor necrosis factor receptors (sTNFRs) during sepsis.
      In baboons, IL-1 alpha induced increased levels of sTNFR types I and II. Infusion
      of Escherichia coli into baboons also led to higher sTNFR levels. Treatment with
      IL-1 receptor antagonist (ra) attenuated the rise in sTNFR-I, which was
      positively correlated with a partial preservation of renal function by IL-1ra. In
      patients with sepsis, treatment with IL-1ra also was associated with lower levels
      of sTNFR-1 but did not influence plasma creatinine levels. IL-1ra did not affect
      sTNFR-II in baboons or humans. These data suggest that IL-1 produced during
      sepsis is involved in increases in sTNFR-I. Such increases during rapidly fatal
      septic shock may in part be explained by an effect on the renal clearance of
      sTNFR-I.

PMID- 7622911
TI  - Interleukin-8 in cerebrospinal fluid from patients with meningitis of different
      etiologies: its possible role as neutrophil chemotactic factor.
AB  - Interleukin (IL)-8 concentrations were analyzed in 70 cerebrospinal fluid (CSF)
      samples from patients with meningitis of different etiologies and in 34 normal
      CSF samples. Patient groups included those with pyogenic meningitis, viral
      meningitis, self-resolving aseptic meningitis without a specific diagnosis, and
      meningitis of other etiologies and normal CSF from patients with and without
      neurologic disease. All samples from patients with pyogenic meningitis (18) but
      only 3 from patients with meningitis of other etiologies and with CSF
      polymorphonuclear leukocyte (PMNL) counts > or = 80% had IL-8 levels > or = 2.5
      ng/mL. IL-8 was above the normal level (< or = 0.5 ng/mL) in samples from 5 of 13
      viral and 8 of 23 self-resolving aseptic meningitis patients and in 7 of 13
      samples from patients with meningitis caused by other microorganisms. There was a
      significant relationship between IL-8 levels and CSF PMNL counts in patients with
      nonpyogenic meningitis. The data suggest a possible role of IL-8 as PMNL
      chemotactic factor in different infections of the subarachnoid space, not only in
      pyogenic meningitis.

PMID- 7622912
TI  - Detection of Chlamydia pneumoniae TWAR in human coronary atherectomy tissues.
AB  - Chlamydia pneumoniae TWAR has been associated with coronary heart disease by
      seroepidemiologic studies and direct detection of the organism in atheromatous
      lesions of coronary arteries and aorta. In this study, 38 fresh tissue specimens
      from patients with coronary artery lesions that were treated by directional
      coronary atherectomy were tested for C. pneumoniae. Twenty-three specimens were
      from patients with primary lesions and 15 were from patients with restenoses. C.
      pneumoniae was detected by polymerase chain reaction (PCR), immunocytochemical
      stain (ICC), or both in 20 of 38 specimens. Using cell identity markers, the
      organism was localized to macrophages. Ultrastructural evidence of the organism
      was found in the 2 specimens examined by transmission electron microscopy, which
      were also positive by both ICC and PCR. C. pneumoniae was found more frequently
      in tissues from restenoses than in primary lesions (P = .17). There was no
      relation between the frequency of detection of the organism and C. pneumoniae
      specific antibody titers.

PMID- 7622913
TI  - Sequence conservation in the major outer membrane protein gene among Chlamydia
      trachomatis strains isolated from the upper and lower urogenital tract.
AB  - To determine the extent of nucleotide sequence variation in the major outer
      membrane protein (MOMP) gene among 27 clinical isolates of Chlamydia trachomatis,
      the MOMP gene was amplified from 13 strains isolated from the endometrium of
      patients with pelvic inflammatory disease and high titers of anti-chlamydial
      antibodies and from 14 strains isolated from the cervix of patients with presumed
      first-time chlamydial infection. Amplified MOMP variable domain DNA from these
      isolates was directly sequenced and compared with previously published results.
      Very little sequence heterogeneity in the MOMP variable domains was found in all
      27 clinical isolates, suggesting that MOMP sequence heterogeneity is not often
      associated with the spread of C. trachomatis to the upper genital tract and is
      not common in the chlamydial strains in the patient population studied.

PMID- 7622914
TI  - Reactivation of Chlamydia pneumoniae lung infection in mice by cortisone.
AB  - To study persistent infection, reactivation of Chlamydia pneumoniae lung
      infection in mice was attempted by immunosuppression with cortisone treatment.
      Four-week-old Swiss-Webster mice were treated with cortisone acetate (125 mg/kg)
      every other day for a total of six doses, starting on day 28 after intranasal
      inoculation of C. pneumoniae AR-39. C. pneumoniae was recovered from the lungs in
      6 of 13 animals after six doses of cortisone, while control animals given saline
      remained negative. C. pneumoniae DNA was detected by polymerase chain reaction in
      the 6 culture-positive mice and 2 of 10 controls. The presence of pathogen DNA in
      this animal model suggested viable organisms in a culture-negative state.

PMID- 7622916
TI  - Acyclovir-resistant herpes simplex virus infection.

PMID- 7622915
TI  - Safety, plasma concentrations, and efficacy of high-dose fluconazole in invasive
      mold infections.
AB  - A trial of the antifungal triazole fluconazole was conducted in cancer patients
      with presumed or proven mold infection. Groups of patients received fluconazole
      at four dosages (800, 1200, 1600, or 2000 mg/day). Adverse events, plasma levels,
      and clinical response were examined. Thirty-nine patients were enrolled. The 28
      evaluable patients had presumed (13 patients) or proven (15) mold infection with
      Aspergillus (4) and Fusarium (3) species, Zygomycetes organisms (1), or
      nonspeciated mold (7). Adverse effects included elevated liver function test
      results (8 patients), nausea and vomiting (2), and erythema multiforme (1).
      Neurologic toxicity occurred in 3 patients receiving 2000 mg/day. Average steady
      state peak plasma concentrations were 51.8, 74.4, and 91.8 mg/L for dosages 1200,
      1600, and 2000 mg/day, respectively. Seven of 28 evaluable patients responded.
      Response did not appear to be related to dose. Fluconazole is well tolerated at
      total daily doses up to 1600 mg. The data suggest a linear plasma concentration
      dose relationship. The activity of fluconazole in refractory mold infections
      seems to be limited.

PMID- 7622917
TI  - Production of cytokines and platelet activating factor in secondary dengue virus
      infections.

PMID- 7622918
TI  - Anti-ganglioside antibodies in patients with Guillain-Barre syndrome and
      Campylobacter jejuni infection.

PMID- 7622919
TI  - Soluble interleukin-6 receptor in patients with severe sepsis.

PMID- 7622920
TI  - Interleukin-8 serum levels for early detection of infectious episodes in
      neutropenic patients.

PMID- 7622921
TI  - Efficacy and safety of desensitization to trimethoprim-sulfamethoxazole in human
      immunodeficiency virus-infected patients.

PMID- 7622922
TI  - Symposium on relapse in leprosy.

PMID- 7622923
TI  - Relapse after MDT in MB cases.

PMID- 7622924
TI  - Social background of leprosy patients in Bombay.

PMID- 7622925
TI  - NSS volunteers--role in leprosy awareness.

PMID- 7622926
TI  - Risk of relapse in leprosy. The Leprosy Unit, WHO.
AB  - Until the introduction by WHO of the standard regimens using multidrug therapy
      (MDT) for the treatment of leprosy, there was a general unwillingness to release
      patients from treatment. This was mainly due to the high risk of relapse after
      dapsone monotherapy. After almost a decade of MDT implementation and after
      releasing more than 4 million patients, it was necessary for WHO to review the
      risk of relapse following WHO-recommended MDT. The results of this study, carried
      out on more than 20,000 MB and 50,000 PB patients, revealed that the risk of
      relapse is very low, 0.77% for MB and 1.07% for PB, nine years after stopping
      MDT. In comparison to dapsone monotherapy, the risk is 10-times lower. Thus, over
      the last decade, MDT implementation has probably prevented close to half-a
      million relapses.

PMID- 7622927
TI  - Issues in evaluating information on relapse in leprosy.

PMID- 7622929
TI  - Epidemiological aspects of relapses in leprosy.
AB  - Life table methods in which the cumulative probability of relapse in successive
      periods is calculated are preferable to the presentation of overall relapse
      rates. Their use facilitates the comparison of relapse rates and trends from
      different studies independent of duration of follow-up. Results from various
      studies including data from Malawi indicate that, (1) unlike after dapsone
      monotherapy, the cumulative probability of relapse in multibacillary patients is
      near to zero after WHO/MDT if strict definitions of relapse are used and, (2) the
      cumulative probability of relapse may approach 5% in paucibacillary patients 10
      years after completion of WHO/MDT. On the whole, the epidemiological relevance of
      relapses is insignificant and future treatment regimens should be evaluated
      concerning their efficacy in preventing disabilities rather than relapses.

PMID- 7622928
TI  - Relapse, reactivation or reinfection?

PMID- 7622930
TI  - Clinical features and diagnosis of relapses in leprosy.
AB  - 1. The definition of relapse as "occurrence of new signs and symptoms of the
      disease during the period of surveillance or thereafter in a patient who
      successfully completes an adequate course of multidrug therapy" accommodates the
      current policy of releasing patients even when there are clinical and
      bacteriological signs of activity after fixed duration treatment. 2. The
      predisposing cause of relapse in the persistence of live M. leprae in various
      tissues in MB leprosy and in the nerve in PB leprosy. 3. The precipitating causes
      of relapse include (a) inadequate therapy due to miscategorization of MB cases as
      PB when there are solitary or few MB lesions since skin smear examinations for
      AFB are not routinely done in PB cases. (b) Previously sulphone treated LL cases
      inactive for more than two years are not included for MDT. Relapses commonly seen
      in NLEP units are in such cases. (c) Multiple skin and nerve lesions in PB
      leprosy. (d) Pregnancy and lactation. (e) Mental depression which downgrades
      immunity. (f) HIV infection. 4. There may be a change in type on relapsing, PB
      cases relapsing as MB and MB cases relapsing as PB. 5. Criteria for diagnosis of
      relapse are: increase in the extent of lesions, infiltration and erythema, fresh
      skin and nerve lesions, positive skin smears for AFB in previously negative
      cases; and in bacteriologically positive cases during surveillance, an increase
      in BI by two logs at any site over the previous BI in two successive
      examinations. 6. Relapses are but too often diagnosed as reversal reactions
      inspite of the absence of symptoms and signs of acute inflammation to the
      detriment of patients; a course of steroid therapy which is administered to these
      patients on the diagnosis of reversal reaction does not halt the progress of the
      disease especially in the nerve, resulting in disability.

PMID- 7622931
TI  - Features of relapse in paucibacillary leprosy after multidrug therapy.

PMID- 7622932
TI  - Histopathological features of relapsed leprosy.

PMID- 7622933
TI  - Immunological aspects of relapse in leprosy.

PMID- 7622934
TI  - Microbiological aspects of relapse in leprosy.

PMID- 7622935
TI  - Treatment of relapsed leprosy.

PMID- 7622937
TI  - The time of occurrence of liver metastasis in carcinoma of the pancreas.
AB  - By measuring the doubling time of liver metastasis, the authors investigated the
      possibility of occult liver metastasis at the time of pancreatectomy in patients
      with pancreatic carcinoma. We calculated tumor doubling times of liver metastases
      in six patients after pancreatectomy for periampullary carcinoma and compared
      with cell doubling times. We also calculated the diameters of the occult liver
      metastases at the time of pancreatectomy on the assumption that the growth rates
      of liver metastasis were constant. Tumor doubling times of liver metastases in
      six patients were 34, 32, 318, 108, 78, and 27 d, respectively. In two of these
      patients, tumor doubling times, compared with cell doubling times of 51 and 52 h
      for PK-36 and PK-59 established from the same patients with carcinoma of the
      pancreas, were about 15 times as long as those of cultured cell lines. The
      calculated sizes of the occult liver metastases at the time of pancreatectomy in
      these six patients were 2.4, 0.14, 19.0, 8.2, 3.5, and 4.2 mm. In five of these
      six patients, the calculated sizes were in the range between 10 microns and 1 cm.
      These results indicated occult liver metastases had already existed in patients
      with carcinoma of the pancreas at the time of pancreatectomy and were too small
      to be detected by imaging technique. We cannot improve survival rates in
      carcinoma of the pancreas by surgical management alone. For further improvement
      in survival rate of patients with carcinoma of the pancreas to occur, effective
      adjuvant therapies to prevent liver metastases must complement surgical
      management.

PMID- 7622938
TI  - Serum beta 2-microglobulin in chronic diseases of the pancreas.
AB  - Elevated serum concentrations of beta 2-Microglobulin (beta 2-MG) has been
      reported in a variety of chronic diseases and solid tumors. We determined serum
      beta 2-MG concentrations in 140 subjects divided into five groups: group 1, 34
      patients with proven chronic pancreatitis, 8 of whom were studied during a
      painful relapse; group 2, 40 patients with pancreatic cancer staged according to
      the Cubilla-Fitzgerald classification; group 3, 40 healthy subjects; group 4, 10
      patients with digestive nonpancreatic carcinomas; group 5, 16 patients with
      benign digestive nonpancreatic diseases. Serum soluble interleukin-2 receptor
      (sIL-2R) was also determined in all patients with pancreatic diseases as an index
      of immune system activation. In addition, serum CA 19-9 was assayed in patients
      of groups 2 and 4, and C-reactive protein (CRP) of groups 1 and 5. Renal
      function, evaluated by serum creatinine determination, was normal in all subjects
      studied. Patients with pancreatic cancer and those with chronic pancreatitis had
      serum concentrations of beta 2-MG significantly higher than those of healthy
      subjects (p < 0.001 and p < 0.005, respectively). Patients with stage I and stage
      III pancreatic cancer had similar serum levels of beta 2-MG, and these
      concentrations were significantly lower than those of patients with stage II
      tumors (p < 0.002 and p < 0.05, respectively). In chronic pancreatitis patients,
      those studied during painful relapse of the disease had serum concentrations of
      beta 2-MG similar to those studied during clinical remission.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7622936
TI  - On the role of cholecystokinin in pancreatic cancer.

PMID- 7622939
TI  - The serum concentration of insulin, C-peptide, and proinsulin in patients with
      acute pancreatitis.
AB  - In 14 patients with acute pancreatitis during 16 episodes of the disease the
      concentrations of blood glucose, serum insulin (IRI), C-peptide (CP), and
      proinsulin (Pro) were determined in the fasting state on d 1, 2, 3, 5, and 10
      after the attack. The peptides were measured using RIAs, and for determination of
      CP two antibodies: Byk-Mallinckrodt's and more specific M-1221 Novo antibodies
      were used. Apart from sporadic rises in the initial period of the disease, the
      blood glucose level did not change significantly and had a decreasing trend. On d
      1 the mean serum IRI level was 0.17 +/- 0.04 (SD) nM, and it decreased on d 5 to
      0.06 +/- 0.04 nM, rising again to 0.11 +/- 0.15 nM on d 10. The serum Pro
      concentration was on the same days: 11.1 +/- 12.6, 4.2 +/- 2.4 and 7.5 +/- 10.8
      pM, whereas the serum CP values determined with M-1221 antibodies were 0.48 +/-
      0.50, 0.34 +/- 0.19, and 0.52 +/- 0.25 nM, respectively. However, when serum CP
      was determined using Byk-Mallinckrodt kits, the concentration on d 1 was 1.90 +/-
      1.12 nM and over the following days it decreased to 1.08 +/- 0.98 nM on d 5 and
      on d 10 it was 1.11 +/- 0.46 nM.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7622941
TI  - Effects of C1-esterase inhibitor in three models of acute pancreatitis.
AB  - The present studies were done to evaluate the therapeutic potential of C1
      esterase inhibitor in three different models of acute pancreatitis: (1) Edematous
      pancreatitis with acinar cell necrosis was induced by 7-h ip injections of 50
      micrograms/kg cerulein in mice; (2) Hemorrhagic pancreatitis was induced by
      feeding a choline-deficient, ethionine-supplemented (CDE) diet in mice; and (3)
      Hemorrhagic pancreatitis was induced by retrograde infusion of 0.6 mL 5% sodium
      taurocholate into the pancreatic duct in rats. C1-esterase inhibitor was given at
      100 mg/kg iv before the onset of pancreatitis and at certain intervals
      thereafter. The severity of pancreatitis was assessed at various times after its
      onset by determination of serum amylase, by grading of histological alterations,
      and by determination of survival (survival determined only in models of
      hemorrhagic pancreatitis). In some of the models, C1-esterase inhibitor slightly
      ameliorated the degree of histological alterations; the increase in serum amylase
      was reduced by C1-esterase inhibitor only in CDE diet-induced pancreatitis. In
      all three models, C1-esterase inhibitor, however, failed to cause major
      beneficial effects and also failed to improve survival in taurocholate- and diet
      induced pancreatitis. Additional studies in 12 patients with acute pancreatitis
      showed that C1-esterase inhibitor activity was markedly increased in serum of all
      patients during the first 9 d of the disease, suggesting that C1-esterase
      inhibitor behaves like an acute phase protein. Taken together the results from
      the animal and the human studies, C1-esterase inhibitor appears to only have a
      limited potential for treatment of acute pancreatitis.

PMID- 7622940
TI  - Chemical structure of the carbohydrate moiety of fucose-rich glycopeptides from
      human pancreatic juice.
AB  - Human pancreatic juice, obtained from nine patients after partial excision of the
      pancreas for bile duct cancer, was fractionated in order to isolate its
      glycopeptides. Three glycopeptides were purified employing ion-exchange
      chromatography and gel filtration. All the glycopeptides were found to be free of
      sialic acid and galactosamine but to have an unusually high content of L-fucose.
      The chemical structures of the three glycopeptides were determined using 500-MHz
      [1H]-NMR spectroscopy. One of them, glycopeptide, GP-4, possessed a biantennary
      structure with three L-fucose residues. The second glycopeptide, GP-3, had a
      triantennary structure with four L-fucose residues, and the third one, G-2, had a
      tetra-antennary structure with five L-fucose residues. The chemical compositions
      of these glycopeptides, including the absence of sialic acid and the high L
      fucose content, indicate that they represent a new class of glycopeptide present
      in the normal human pancreas.

PMID- 7622942
TI  - Long-term effects of alloxan in mice.
AB  - The long-term effects of subdiabetogenic doses of alloxan monohydrate (< 70
      mg/kg) were studied in the mouse. When injected intravenously at 50 and 60 mg/kg,
      alloxan induced a marked albeit transient hyperglycemia; plasma levels gradually
      declined after 15 d and were normal after 60 d in 20 of 31 animals. After
      injection of alloxan at the dose of 40 mg/kg, only a slight transient
      hyperglycemia was seen during the first 15 d. At 2 mo after alloxan injection,
      however, glucose- and carbachol-stimulated insulin secretion were markedly
      impaired in all animals treated with alloxan, including those with normoglycemia.
      The pancreatic content of insulin was significantly reduced at 2 mo after
      treatment of alloxan at 50 or 60 mg/kg, but, however, not after 40 mg/kg. It is
      concluded that (1) Subdiabetogenic doses of alloxan (50 and 60 mg/kg) induce a
      persistent hyperglycemia only in approx 25% of the animals; (2) The insulin
      secretory responses to glucose and carbachol are impaired after alloxan
      treatment; and (3) Alloxan-induced B-cell toxicity is evident also in animals not
      developing permanent diabetes. Hence, although a repair process may be initiated
      after alloxan to normalize the hyperglycemia, insulin secretion and pancreatic
      insulin content do not normalize.

PMID- 7622943
TI  - Resolution of refractory pancreatic ascites after continuous infusion of
      octreotide acetate.
AB  - The treatment of pancreatic ascites remains a clinical challenge. Both medical
      and surgical management have high rates of mortality and recurrence. New methods
      in the treatment of pancreatic ascites are actively sought. We describe the
      successful use of a continuous infusion of octreotide acetate in the treatment of
      refractory alcoholic pancreatic ascites.

PMID- 7622944
TI  - Annular pancreas associated with carcinoma in the dorsal part of pancreas
      divisum.
AB  - A carcinoma in the dorsal part of the pancreas divisum with an annular pancreas
      in the anterior part is reported. A 79-yr-old female was admitted in our hospital
      complaining of epigastralgia. Computed tomography (CT) and ultrasound (US) showed
      an irregular mass in the pancreatic body. A pancreatogram obtained through the
      major duodenal papilla demonstrated only the ventral pancreatic duct that
      encircled the duodenum. Contrast medium injected from the minor duodenal papilla
      showed Santorini's duct obstruction at the neck portion of the pancreas without
      communication with the ventral pancreatic duct. The patient died with liver
      metastases. Autopsy confirmed annular pancreas and a 6-cm tumor in the pancreatic
      body extending to the pancreatic head and pancreas divisum. Pancreatic carcinoma;
      histologically a moderately differentiated adenocarcinoma; originated from the
      dorsal part of pancreas divisum. To our knowledge this is the first report of
      pancreatic carcinoma associated with annular pancreas coexistent with pancreas
      divisum.

PMID- 7622945
TI  - Staging of pancreatic cancer: suggestions for a simplified, reliable modification
      of the TNM classification system.

PMID- 7622946
TI  - Nursing management of cranial nerve dysfunction.
AB  - Cranial nerve dysfunction is frequently seen in neuroscience patients. Deficits
      range in severity and can present many challenges for nurses. Patients are at
      risk for complications such as worsening vision, corneal damage, improper
      nutrition, aspiration and respiratory difficulty. With a proper understanding of
      how to manage these patients, nurses can perform interventions that will minimize
      complications and assure better outcomes for the patient. Multidisciplinary care
      is often needed for these patients but it is the nurse who is in a pivotal role
      to provide appropriate care, coordinate the multidisciplinary needs and offer
      patient and family education and support.

PMID- 7622947
TI  - Arteriovenous malformation in the pregnant patient: a case study.
AB  - Subarachnoid hemorrhage (SAH) due to ruptured arteriovenous malformation (AVM) or
      aneurysm accounts for 4.4% of all maternal deaths. It is the third most common
      nonobstetric cause of maternal death. Significant differences, such as timing of
      the initial bleed and rebleeding, exist between aneurysmal and AVM related SAH.
      Increased risk of AVM related SAH appears to correlate with the augmented cardiac
      output of pregnancy, as well as with other coagulation, hemodynamic and
      endocrinological changes. These changes usually occur between 20 weeks gestation
      and 6 weeks postpartum. All suspicious neurological signs and symptoms in the
      gravid patient should be thoroughly evaluated. Although the nursing care of the
      pregnant patient with an AVM is similar to that of nonpregnant patients, there
      are specific clinical observations that are relevant to these patients.

PMID- 7622948
TI  - One family's experience with head injury: a phenomenological study.
AB  - A phenomenological approach was used in this study to describe the lived
      experience of one family with traumatic brain injury. All seven family members
      were interviewed regarding their thoughts and memories from the night of the
      accident through the acute stage and initial rehabilitative stage. Three themes
      captured the essence of the experience as described by the parents and siblings:
      "helplessness and the need to hope," "need to be informed and involved" and
      "impact of intubation/extubation." The victim's unique perspective was captured
      by the themes: "going home," "concern for others" and "piecing it together."
      Hermeneutic interpretations examine the transformative and enriching aspects as
      well as the disruptions and problems associated with the family experience of
      traumatic brain injury.

PMID- 7622950
TI  - Use of think aloud method to study nurses' reasoning and decision making in
      clinical practice settings.
AB  - The purpose of this article was to describe the use of TA method to study nurses'
      reasoning and decision making in a neurosurgical setting. The feasibility and
      benefit of the method were explored, and examples were provided from data
      collected on a neurosurgical unit during the immediate post operative care of
      craniotomy patients. The authors hope that this report will encourage other
      investigators to consider using this method to examine nurses' reasoning and
      decision making. They also hope that future investigators will be encouraged to
      move TA to clinical practice settings, rather than continuing to rely on
      simulations, which can never fully replicate the realities of clinical practice.

PMID- 7622949
TI  - Pharmacological interventions for agitation in head-injured patients in the acute
      care setting.
AB  - Agitation following head injury challenges nurses to provide patient safety and
      participation in daily care and therapies. Diagnosis of the underlying disorder
      which causes agitative behavior is essential for rapid and successful treatment.
      A combination of pharmacological and nonpharmacological interventions are
      required to achieve this expected outcome. Propofol, lorazepam, midazolam and
      haloperidol are medications most commonly utilized in this patient care
      situation. The patient's sedation level should be monitored to avoid oversedation
      which may interfere with respiration and neurological status. Nurses need to
      understand the actions and adverse effects of these agents in order to advocate
      their proper usage in the agitated head-injured population.

PMID- 7622951
TI  - Paying for it.

PMID- 7622952
TI  - Managed care.

PMID- 7622953
TI  - Intrahospital transport of neuro ICU patients.
AB  - Neuroscience intensive care unit (NICU) patients are frequently transported out
      of the critical care environment for diagnostic and interventional procedures.
      Four hundred and seventy-one such transports from seventeen clinical centers were
      studied to identify the characteristics of intrahospital transport. Data
      collected included the destination and duration of transport, number and type of
      personnel involved, changes in monitoring and treatment during transport, adverse
      patient responses and the impact on patients left in the unit. Differences
      between transports characterized as elective or emergent in nature were noted.
      Results validate that intrahospital transport of NICU patients is both time and
      labor intensive. The study also suggests that the optimal process for safe and
      efficient transport is yet to be designed.

PMID- 7622954
TI  - Neuroendoscopic third ventriculostomy: a nursing perspective.
AB  - Endoscopic third ventriculostomy is an old technique that has gained greater
      acceptance in recent years with the advent of new endoscopic technology. This
      procedure, which involves fenestrating the floor of the third ventricle to
      communicate the basilar cisterns with the third ventricle offers new hope to
      patients with non-communicating hydrocephalus. Until recently, the only accepted
      treatment for these patients was the placement of a ventriculoperitoneal shunt to
      drain the accumulating cerebrospinal fluid. It is well known that shunting
      carries the risks of infection, blockage and overdrainage. This technique
      provides an alternative to a less than perfect treatment for reestablishing CSF
      pathways. Patients best suited for the procedure have delayed onset aqueductal
      stenosis caused by a tumor, cyst or hemorrhagic event. Patients with aqueductal
      stenosis as a consequence of myelomeningeocele fare less well, but show better
      success with the technique if it is performed as a follow-up to shunting rather
      than as an initial procedure. Several techniques may be used to perform third
      ventriculostomy. An understanding of the special needs of the patient undergoing
      the procedure is essential to optimum care.

PMID- 7622956
TI  - The role of the neuroscience nurse in lumbar fusion.
AB  - Lumbar spinal fusion is a major surgical procedure that joints together two or
      more vertebral bodies to restore stability to the lower spine. Spinal fusion may
      be indicated as a result of a variety of causes. Regardless of the underlying
      problem, if instability of the spine occurs, fusion may be necessary. In recent
      years there have been a number of new spinal instrumentation systems introduced
      that provide stabilization and immobilization of the spine while bony fusion
      occurs. Neuroscience nurses must be prepared to care for patients undergoing this
      procedure as their ability to educate, assess and intervene throughout the
      perioperative period can have a positive effect on the outcome of lumbar spinal
      fusion.

PMID- 7622955
TI  - Coping and marital equilibrium after stroke.
AB  - This study explored the effects of a cerebrovascular accident on seven older
      couples. The long interview method was used to identify major themes in seven
      couples' accounts of their post-stroke effects. Four major themes emerged which
      included experiencing physical changes, feeling down and worrying about the
      future, being restricted and adjusting to limits and seeking a new balance in the
      marriage. Stroke survivors and spouses differed in how they described the impact
      of the stroke for older couples. Support groups and family counseling may be used
      to facilitate couple adaptation after stroke. Longitudinal research is needed to
      explore adaptive coping post-stroke in both stroke survivors and stroke spouses.

PMID- 7622958
TI  - Descending thoracic aorta to femoral artery bypass.
AB  - Anatomic placement of a synthetic graft from the infrarenal aorta to the
      iliofemoral vessels has been a long recognized technique used to bypass occlusive
      disease of the distal aorta and iliofemoral arteries. However, in a few select
      patients with failure or infection of the abdominal graft, or in patients with a
      "hostile" abdomen from multiple prior operations, the descending thoracic aorta
      may be used as an inflow source for the iliofemoral vessels. This paper will
      discuss the indications, patency data, and technique of descending thoracic aorta
      to femoral artery bypass with a case presentation.

PMID- 7622959
TI  - An exploratory study of the experiences of rural women with breast cancer.
AB  - Patient adjustment to chronic illness is influenced by various cultural factors.
      This study examined some of the issues faced by rural patients in adjusting to
      the diagnosis of breast cancer. A sample of 10 women who had been diagnosed with
      breast cancer from 12-36 months prior to the study were recruited from a variety
      of sources. Using a long-interview qualitative research format, each patient was
      questioned about her reactions to her illness and relationship with medical
      providers. Interviews were taped recorded and the texts were transcribed and
      analyzed using an editing-analysis format with a multidisciplinary analysis team.
      As might be expected, patients reactions to their illness and health care
      providers varied considerably. Notable findings were a sense of urgency for
      treatment after diagnosis and a general sense of dissatisfaction with patient
      physician communications. This group of rural women with a life-threatening
      cancer expressed a greater need for information and collaborative decision making
      than was met by their oncologists. Further exploration of this hypothesis would
      be helpful to determine how prevalent these opinions are among rural patients.

PMID- 7622957
TI  - Continuous midazolam/atracurium infusions for the management of increased
      intracranial pressure.
AB  - Maintaining the pressure/volume balance in the brain is a challenging goal for
      the neuroscience team caring for patients with traumatic brain insults. Often,
      standard therapies are not effective in controlling increased intracranial
      pressure (ICP). Four severe traumatic brain injury patients given continuous
      infusions of midazolam and atracurium showed control of otherwise unstable ICPs.
      Midazolam and atracurium infusions are now considered an acceptable form of
      therapeutic intervention for our patients requiring such treatment. Intensive
      nursing care considerations for patients using the combined pharmacologic therapy
      are essential.

PMID- 7622961
TI  - The lesson of humility.

PMID- 7622960
TI  - Physicians for the 21st century: implications for medical practice, undergraduate
      preparation, and medical education.
AB  - Changes in medical education and the practice of medicine have resulted from the
      push for both education and health care reforms. Undergraduates planning
      application to medical school should broaden their preparation to include
      communications, computers, economics, and multicultural educational experiences.
      To prepare graduates for medical practice in the new millennium, the University
      of Kentucky College of Medicine has implemented a new curriculum focusing on
      integration of basic and clinical sciences, primary care in ambulatory sites,
      health promotion and disease prevention, and attention to the ethical, social,
      psychologic, and financial impact of disease upon the patient, family, and
      society.

PMID- 7622962
TI  - Avoiding a two-tiered medical system.

PMID- 7622963
TI  - Growing up dyslexic: a parent's view.

PMID- 7622964
TI  - The influence of affect on the achievement and behavior of students with learning
      disabilities.
AB  - Research indicates that students with learning disabilities are likely to be at
      greater risk for experiencing negative affect than their higher achieving
      counterparts. The purpose of this article is to review recent research on the
      effects of affect on thoughts, cognition, and behavior. This research finds that
      induced positive affects leads to more accurate performance on math, greater
      learning of new vocabulary, and better performance on a new learning task.
      Implications of and suggestions for follow-up studies of negative and positive
      affect in students with learning disabilities are presented.

PMID- 7622965
TI  - Family patterns of reaction to a child with a learning disability: a mediational
      perspective.
AB  - The impact of a child's learning disability on the family system is explored with
      regard to the general consequences for the system and to the parents' abilities
      to react to the problems generated for the child and family. Feuerstein's concept
      of mediated learning experience is proposed as a useful way of understanding the
      process issues, to assess parental reactions, and to guide more productive and
      adaptive interventions. Four prototypical patterns of family response are
      presented, with descriptions of the mediational restrictions and potentialities
      embedded within them. Implications are presented for both dysfunctional responses
      and the development of positive and adaptive reactions.

PMID- 7622966
TI  - Phonetic coding and reading in college students with and without learning
      disabilities.
AB  - This study examined whether adult speech production and oral reading were related
      independent of auditory short-term memory and vocabulary. Forty-four university
      students served as subjects for the study. They ranged in age from 17 to 28 years
      old; 26 were men and 18 were women; 11 were students with learning disabilities
      and 33 were students without disabilities. All subjects were tested individually
      on tasks requiring multisyllabic pseudoword repetition, oral reading, memory for
      digits, and vocabulary. In both groups--with and without learning disabilities-
      significant correlations were found between pseudoword repetition accuracy and
      reading, suggesting that poor readers also have more inaccurate speech
      production. The correlations remained significant after controlling for both
      memory and vocabulary. A scatter plot of the speech-reading relationship showed
      performance overlap between groups, as well as within-group heterogeneity.
      Significance of the findings is discussed, and issues for future research are
      identified.

PMID- 7622967
TI  - Topical issues education: teaching controversial or sensitive topics to students
      with learning disabilities.
AB  - This study investigated the extent to which a sample of 407 special education
      teachers addressed various topical issues with students who have learning
      disabilities, mental retardation, or behavior disorders. A survey instrument was
      employed to gather information pertaining to 45 topical issues that involve
      controversial or sensitive subjects typically not addressed in the traditional
      academic curriculum in school. Results indicated that the majority of topical
      issues are addressed only to a very limited extent with students with
      disabilities. A 3 x 2 factorial analysis of variance, followed by post hoc
      comparisons using Scheffe's test, indicated that topical issues are addressed to
      the greatest extent with students with behavior disorders and to the least extent
      with students with learning disabilities. Results also indicated differences in
      the extent to which elementary- and secondary-level students with disabilities
      receive information from special education teachers about topical issues, with a
      greater emphasis on coverage of topical issues occurring at the secondary level.
      Possible explanations for the findings are discussed, followed by implications
      for special education teachers and recommendations for future research involving
      topical issues education for students with learning disabilities.

PMID- 7622968
TI  - Self-perceptions and social comparisons among children with LD.
AB  - The self-perceptions of third- and fourth-grade children with learning
      disabilities (LD; n = 59) and nondisabled students (n = 57) were compared using
      the Self-Perception Profile for Learning Disabled Students. Results suggested
      that the children with LD perceived themselves as less competent than did the
      controls in the areas of intelligence, academic skills, behavior, and social
      acceptance. These differences were not related to the length of time subjects
      with LD had received special education services. Contrary to expectations,
      subjects' self-perceptions were not affected by whether they chose LD or general
      education class peers as a reference group.

PMID- 7622969
TI  - The impact of adults' communication clarity versus communication deviance on
      adolescents with learning disabilities.
AB  - Research has demonstrated that confusing styles of parental communication-
      "communication deviances" (CD)--are associated with cognitive disorder in
      offspring. The present study examined the immediate effects of adult
      communication clarity versus deviance on sixty-one 11- to 15-year-old male and
      female adolescents with learning disabilities (LD). Subjects were randomly
      assigned to complete the Rorschach Arrangement Task (RorAT) under conditions of
      either clear (n = 30) or unclear (n = 31) instructions from an adult. Immediately
      thereafter, the adolescents were administered a test of abstract thinking--The
      Twenty Questions Task (TQT). Strategies used to solve the task were assessed. As
      hypothesized, adolescents in the clear communication condition performed
      significantly better on the RorAT and used more efficient cognitive strategies on
      the TQT than did adolescents in the unclear communication condition. A new theory
      with implications for teaching and parenting is proposed for understanding the
      influence of adult communication on students with LD.

PMID- 7622970
TI  - Prevalence of coronary artery disease in patient with valvular heart disease.
AB  - The prevalence of coronary artery disease in valvular disease was 10.9 per cent.
      The prevalence of coronary artery disease was more common in males, increasing
      age, aortic valvular disease and mitral regurgitation with chest pain, other
      types of valvular lesions did not correlate with the presence of coronary artery
      disease. The prevalence of significant coronary artery disease especially three
      vessel disease was relatively rare in those aged < 50 years. We recommend
      performing coronary arteriography only in patients aged > 50 years regardless of
      symptoms of chest pain, especially in aortic valvular disease and mitral
      regurgitation.

PMID- 7622971
TI  - Production of monoclonal antibody against hepatitis B surface antigen.
AB  - HBV infection is a major health problem in Southeast Asia. Thailand is considered
      to be an endemic area of HBV infection(18). Prevalence of HBsAg carriers is 5.2
      per cent in children, 9 per cent in adults and 5.6 per cent in pregnant
      women(19,20). We believe that the monoclonal antibody described in the present
      report will be useful to develop HBsAg-KIT for national serologic screening
      assay, as considered in terms of sensitivity, specificity and cost effectiveness.

PMID- 7622973
TI  - The effect of discontinuous Percoll gradient centrifugation on sperm morphology
      and nuclear DNA normality.
AB  - To determine the improvement of sperm morphology and sperm nuclear DNA normality
      after discontinuous Percoll gradients preparation, sperm morphology and sperm
      nuclear DNA normality from 157 semen samples from 45 donors and 63 male partners
      of infertile couples were assessed before and after discontinuous Percoll
      gradients preparation. In semen samples, about 67.5 per cent of the nuclei
      exhibited green acridine orange fluorescence. The percentage of normal sperm
      morphology, percentage of progressive motility, and percentage of green
      fluorescing sperm were significantly better after this sperm preparation.
      Therefore, this sperm preparation technique is a convenient and efficient method
      to select progressive motile, normal morphological and normal nuclear DNA sperm
      for assisted conceptive technology.

PMID- 7622972
TI  - The treatment of chronic suppurative otitis media and otitis externa with 0.3 per
      cent ofloxacin otic solution: a clinico-microbiological study.
AB  - .3 per cent ofloxacin solution has been studied widely and has been proved to be
      safe in both animal and human studies. Ototoxicity and hair cell damage were not
      found in animal experiments. Ototopical treatment in both pediatric and adult
      patients was proved to be safe in previous studies. P. aeruginosa and S. aureus
      play the major role in both CSOM and OE, and most causative pathogens are
      susceptible to ofloxacin. This study showed that the use of 0.3 per cent
      ofloxacin otic solution was safe in both children and adults and yielded
      excellent clinical results.

PMID- 7622974
TI  - Evaluation of current antepartum fetal tests.
AB  - Three hundred high-risk pregnancies of at least 28 weeks' gestation were included
      in this prospective descriptive study. Fetal movement count was performed daily.
      Maternal perception of sound provoked fetal movement (MPSPFM), fetal acoustic
      stimulation test (FAST), amniotic fluid index (AFI) and doppler umbilical artery
      pulsatility index were tested weekly until delivery. All fetal testing performed
      within a week of delivery was compared with fetal outcome. Fetal outcome was
      considered poor when there was perinatal death, intrapartum fetal distress, a
      five minute Apgar score of less than 7, thick meconium-stained amniotic fluid or
      admission to the neonatal intensive care unit. Seventeen pregnancies were
      considered poor outcome (prevalence of 5.7%). Sensitivity, specificity, positive
      predictive value (PPV), negative predictive value (NPV) and Kappa index (KI) of
      each test to predict poor fetal outcome were evaluated. A combination of FAST and
      AFI is the most reliable antepartum fetal test. The sensitivity, specificity,
      positive predictive value, negative predictive value, accuracy and Kappa index of
      the combination of FAST and AFI were 70.0%, 99.6% 87.5%, 98.8%, 98.5% and 0.77%,
      respectively.

PMID- 7622975
TI  - Ten year review of brain abscess in Children's Hospital Bangkok, Thailand.
AB  - Brain abscesses are the most common form of intracranial suppurative process in
      children. In ten years, 54 cases of brain abscess in the Children's Hospital,
      Bangkok were diagnosed mostly on the basis of clinical features, roentgenogram,
      CT scanning and basic laboratory findings. The age distribution of brain abscess
      was from 3 months to 14 years. Evidence of signs of increased ICP was frequently
      present. Almost half of the patients had associated congenital heart disease
      particularly Tetralogy of Fallot. CT scanning was very useful in the advantage of
      rapid diagnosis, early management and short and long-term follow-up, by
      decreasing the mortality of the patients. Definite diagnosis must be established
      by obtaining pus or infected ncrotic brain for culture. Brain abscess bacteria
      can be recovered from properly performed culture. In our series, anaerobic
      peptostreptococci was the organism most frequently encountered. In the present
      series, the mortality rates for antibiotic alone and for antibiotic plus
      aspiration or followed by excision showed no significant difference. Most of
      deaths were due to brain herniation. It is concluded that with earlier diagnosis,
      with CT scanning technology, with appropriate antibiotics and with the use of
      proper surgical methods, the mortality rate from brain abscess should be zero and
      neurological deficit should be reduced as well.

PMID- 7622976
TI  - The impact of routine preoperative complete blood count (CBC) in elective
      operations in Srinagarind Hospital.
AB  - Because anemia and infectious diseases are still common, routine preoperative
      complete blood count (CBC) is often performed in most teaching hospitals in
      Thailand. However, there is growing consensus that it is of little benefit. We
      studied prospectively all patients who were scheduled for elective operation in
      Srinagarind Hospital. Medical history and physical examination were obtained
      prospectively without knowing the CBC result. Out of 1,013 patients interviewed,
      955 were suitable for study, 384/955 (40.2%) of the CBC were abnormal.
      Significant anemia (hematocrit less than 30%) was found in 42 (4.4%),
      leukocytosis in 113 (11.8%), inadequate platelet in 3 (0.3%). The CBC
      abnormalities led to a change in management in 38 (4.0%). The clinical predictors
      of CBC abnormalities included weight loss, history of fever, presence of anemia
      and tender abdomen. In those with normal history and physical examination, the
      prevalence of anemia and CBC which led to management change was less than 1.7 per
      cent, regardless of age.

PMID- 7622977
TI  - Persistently elevated serum transcobalamin II in a patient with cerebral malaria
      and typhus infections.
AB  - A 25-year-old man presented with a history of fever, chills and vomiting for
      three days. The parasite count was 207 ring-forms of P. falciparum per 1000 red
      cells. He developed hemoglobinuria and excreted hemoglobin in the urine 0.20-0.30
      g/dl for 14 days during admission. Many blood transfusions were administered for
      correcting anemia. Although the malarial parasites disappeared one week after
      anti-malarial therapy, however, the fever and hemoglobinuria persisted. The Weil
      Felix reaction OXK was positive with a titre of 1:40 on admission and increased
      to 1:160 on the second week. Chloramphenical and prednisolone were given for
      treatment of typhus fever and all symptoms subsided. Serum TCII levels were found
      to be increased and persisted high during the hemoglobinuria. The clearance of
      TCII was lower and increased relatively slowly to the normal level on day 30. On
      the other hand, TCII excretion in the urine was found to be increased during
      hemoglobinuria. These findings indicate that the catabolism and clearance of TCII
      in this patients is impaired with increased TCII excretion in the urine in
      parallel to the hemoglobinuria. Serum TCII level is, therefore, increased and
      persistently high in a patient with malaria and typhus fever infections with
      hemoglobinuria.

PMID- 7622978
TI  - Vitamin B12, folic acid, ferritin and haematological variables among Thai
      construction site workers in urban Bangkok.
AB  - Serum vitamin B12, folic acid, ferritin and haematological variables were
      investigated in eighty-seven male and nineteen female construction site workers
      in Bangkok. Haemoglobin concentration, haematocrit and MCHC were found to be
      higher in male than in female workers. Serum ferritin was slightly higher in
      males than in females. Serum B12 was found to be higher in male than in female
      workers and serum folic acid level were significantly higher in female than in
      male workers. Vitamin B12 deficiency was found in 2.3 per cent and folic acid
      deficiency in 6.9 per cent of the male workers. Serum vitamin B12 and folic acid
      levels were normal for female workers. The adequate serum levels of vitamin B12
      and folic acid might be the result of the habit of the workers to consume tonic
      drinks which contain glucose, caffeine, and vitamins especially vitamins B6, and
      B12.

PMID- 7622979
TI  - Reversible delirium after discontinuation of fluoxetine.
AB  - An elderly patient developed confusion, disorientation and visual hallucination
      twice following discontinuation of fluoxetine. The mental symptoms, however,
      disappeared after ingestion of this antidepressant drug. Such an apparent
      withdrawal complication of fluoxetine has not been reported previously.

PMID- 7622980
TI  - Tracheal collapse after thyroidectomy: case report.
AB  - One case of tracheal collapse in a series of 116 thyroidectomy is reported. The
      patient presented with multinodular goiter. The tracheal collapse developed after
      removal of the endotracheal tube. A tracheostomy was performed and retained for
      16 days. Follow-up at 1, 3 and 6 months revealed a satisfactory outcome.

PMID- 7622981
TI  - Food-deprivation effects on punished schedule-induced drinking in rats.
AB  - Food-deprived rats (at 80% of their free-feeding weights) were exposed to a fixed
      time 60-s schedule of food-pellet presentation and developed schedule-induced
      drinking. Lick-dependent signaled delays (10 s) to food presentation led to
      decreased drinking, which recovered when the signaled delays were discontinued. A
      major effect of this punishment contingency was to increase the proportion of
      interpellet intervals without any licks. The drinking of yoked control rats,
      which received food at the same times as those exposed to the signaled delay
      contingency (masters), was not consistently reduced. When food-deprivation level
      was changed to 90%, all master and yoked control rats showed decreases in
      punished or unpunished schedule-induced drinking. When the body weights were
      reduced to 70%, most master rats increased punished behavior to levels similar to
      those of unpunished drinking. This effect was not observed for yoked controls.
      Therefore, body-weight loss increased the resistance of schedule-induced drinking
      to reductions by punishment. Food-deprivation effects on punished schedule
      induced drinking are similar to their effects on food-maintained lever pressing.
      This dependency of punishment on food-deprivation level supports the view that
      schedule-induced drinking can be modified by the same variables that affect
      operant behavior in general.

PMID- 7622983
TI  - Within-session changes in the VI response function: separating food density from
      elapsed session time.
AB  - Previous studies examining the relationship between response rate and
      reinforcement rate on variable-interval schedules (the variable-interval response
      function) have confounded elapsed session time with within-session changes in
      food density. The present experiments attempted to manipulate these factors
      independently and thus isolate their effects on responding. In Experiment 1, 7
      rats pressed a bar for food on a series of four variable-interval schedules (7.5
      s, 15 s, 30 s, and 480 s). Elapsed session time was held constant while food
      density was manipulated via a presession feeding. Changes in food density altered
      the form of the variable-interval response function, independently of elapsed
      session time. In Experiment 2, 8 rats responded on the same series of variable
      interval schedules as in Experiment 1, but food density was held constant and
      elapsed session time was manipulated via the use of timeout periods. The results
      revealed no evidence for an effect of elapsed session time independent of food
      density. The present results extend a recent analysis of the variable-interval
      response function by Dougan, Kuh, and Vink (1993) by identifying food density as
      an important factor determining the form of the function. The present results
      also help clarify the controversy over the correct empirical form of the variable
      interval response function by further defining the variables responsible for
      differences in the form of that function.

PMID- 7622982
TI  - Cocaine's effects on food-reinforced pecking in pigeons depend on food
      deprivation level.
AB  - Four pigeons deprived to 80% of their laboratory free-feeding weights pecked keys
      under a multiple fixed-ratio 30 fixed-interval 5-min schedule of food
      presentation. Components alternated strictly with 15-s timeouts separating them;
      each was presented six times. When rates of pecking were stable, 2 pigeons'
      weights were reduced to 70%, and the other 2 pigeons' weights were increased to
      82.5% to 85% of free-feeding levels. Cocaine (1.0, 3.0, 5.6, and 10.0 mg/kg and
      saline) was administered 5 min prior to sessions. When each dose had been tested
      twice, pigeons' weights were adjusted to the level that they had not yet
      experienced, and cocaine was tested again. Cocaine reduced response rates in a
      dose-dependent manner under the fixed-ratio schedule and under the fixed-interval
      schedule at high doses, and increased rates under the fixed-interval schedule at
      low low doses. Reductions in pecking rates occurred at lower doses under both
      schedules in 3 of 4 pigeons when they were less food deprived compared to when
      they were more food deprived. Low doses of cocaine increased low baseline rates
      of pecking in the initial portions of the fixed-interval schedules by a greater
      magnitude when pigeons were more food deprived. Thus, food-deprivation levels
      altered both the rate-decreasing and rate-increasing effects of cocaine. The
      implications of these results for the mechanisms by which food deprivation
      increases cocaine self-administration and for the dependence of cocaine's effects
      on the baseline strength of operant behavior are discussed.

PMID- 7622984
TI  - Infant memory for object motion across a period of three months: implications for
      a four-phase attention function.
AB  - Memory for object motion in 3-month-old infants was investigated across retention
      intervals of 1 or 3 months in three studies using a novelty preference method.
      Following familiarization to an object undergoing one of two types of motion,
      visual preferences for the novel motion were assessed after retention intervals
      of 1 min, 1 day, and 1 month (Experiment 1, N = 120) and 1 min, 1 day, 2 weeks,
      and 1 month (Experiment 2, N = 74). Results of both studies indicated a
      significant preference for the novel motion at the 1-min delay, a significant
      preference for the familiar motion at the 1-month delay, and no preferences at
      the intermediate retention intervals. In Experiment 3, memory was assessed after
      a 3-month interval and again, a significant familiarity preference was obtained.
      These results demonstrate that memory for object motion lasts across retention
      intervals of 1 and 3 months and that novelty and familiarity preferences interact
      with retention time. A four-phase function relating visual preferences and
      retention time was proposed. Phase 1, recent memory, is characterized by a
      novelty preference; phase 2, intermediate memory, is a period of transition
      characterized by no visual preference; phase 3, remote memory, is characterized
      by a familiarity preference; and phase 4, inaccessible memory, is also
      characterized by no preference. The finding of a transition period at
      intermediate retention times suggests that null preferences should not
      necessarily be taken as evidence of forgetting. Rather, more extended retention
      intervals should be included to interpret null findings obtained in the novelty
      preference method.

PMID- 7622985
TI  - Effects of postevent information on infants' memory for a central target.
AB  - In three experiments with 78 infants, we explored the effect of introducing novel
      information about a central target after a short delay on 6-month-olds'
      recognition of the original target, the novel exposure target, and a completely
      novel one. In all experiments, infants learned to move a particular crib mobile
      (the central target) by kicking and then were exposed to a novel mobile (the
      conflicting postevent information) immediately after training was over. In
      Experiment 1, memory for the original mobile was unimpaired, but infants treated
      both the exposure mobile and a completely novel one as if they had actually been
      present originally. In Experiment 2, only a completely novel mobile was an
      effective remainder in a reactivation paradigm, indicating that the impact of
      postevent information was relatively long-lasting and that the failure of the
      other mobiles to recover the training memory resulted from trace competition at
      the time of retrieval. In Experiment 3, identical novel information did not
      proactively affect recognition. Thus, 6-month-olds' memory of a central target is
      resistant to impairment by conflicting postevent information after a short delay,
      but they are highly prone to source misattribution. We propose that postevent
      information effects are cognitively efficient.

PMID- 7622986
TI  - Working memory in infancy: six-month-olds' performance on two versions of the
      oculomotor delayed response task.
AB  - The capacity of 6-month-old infants to maintain information in working memory for
      several seconds was studied using two versions of an oculomotor delayed response
      task. Infants were presented with either a cue stimulus in a target location
      (Experiment 1), or an abstract, central stimulus (Experiment 2) which could be
      used to predict the peripheral location in which an attractive target stimulus
      subsequently appeared. Eye movements during delay periods from 600 to 5000 ms
      were recorded. The results indicated that infants maintained information about
      stimulus locations in working memory for 3-5 s. These results imply maturity of
      regions of the prefrontal cortex closely associated with a similar task used in
      neurophysiological and neuroimaging studies.

PMID- 7622987
TI  - Evidence of robust recognition memory early in life even when assessed by
      reaching behavior.
AB  - Infants of only 5-6 months prefer to look at something new when given the choice
      of looking at a stimulus shown earlier or something new, even after a long delay
      (the visual paired comparison task). However, if infants must reach and displace
      a stimulus to retrieve a reward, even 18-month-olds respond randomly when given
      the choice of reaching to the stimulus shown earlier or to something new, even
      after a brief delay (the delayed nonmatching to sample task). To investigate this
      paradox we modified the delayed nonmatching to sample task to make it more
      similar to visual paired comparison. Each stimulus served as its own reward; no
      rewards were hidden under any stimuli. Infants were habituated to a sample
      object, a delay was imposed, and then the sample and a new object were presented.
      Infants could choose to look at (in visual paired comparison) or reach for (in
      delayed nonmatching to sample (stimulus = reward)) either object. One hundred
      twenty infants were tested: 60 (20 each at 4, 6, and 9 months) on visual paired
      comparison and 60 (20 each at 6, 9, and 12 months) on delayed nonmatching to
      sample (stimulus = reward). The same 10 pairs of stimuli were used on both tasks.
      Each subject was tested twice at all five delays (10, 15, 60, 180, and 600 s). At
      even the youngest age that reaching was tested (6 months), infants showed
      evidence of recognition memory on the reaching task at delays at least as long as
      those at which they demonstrated recognition memory on the looking task. Indeed,
      when subjects reached, not in order to obtain something else, but to obtain the
      stimulus itself, they succeeded on a recognition memory task even at delays 10
      min long very early in life.

PMID- 7622988
TI  - Long-term recall of event sequences in infancy.
AB  - The first experiment shows that 11-month-olds can encode novel causal events from
      a brief period of observational learning, and recall much of the information
      after 24 h. The second experiment, using both a longitudinal and a cross
      sectional design, shows recall of the same events after a delay of 3 months. The
      infants remembered more individual actions than whole sequences, but reproduced
      many of the events in their entirety (and always in correct order) after the long
      delay. Although they also reproduced arbitrarily ordered events immediately after
      being shown them at 11 months, they began to forget them after 24 h and showed
      essentially no recall for this type of event after 3 months. The experiments not
      only indicate long-lasting memory for briefly experienced events in infancy, they
      also suggest that the factors that organize recall at this young age are similar
      to those found in older children and adults.

PMID- 7622989
TI  - One- to two-year-olds' recall of events: the more expressed, the more impressed.
AB  - The literature on stylistic differences in mother-child conversations about
      ongoing and past events can be interpreted to suggest that the opportunity to
      verbally elaborate on an event facilitates preschoolers' memory. In this research
      we examined whether similar effects would obtain in children who are just
      acquiring language and, thus, the opportunity for verbal encoding. Using elicited
      imitation, 12 groups, formed by a between-subjects crossing of 3 levels of age
      (13, 16, and 20 months) with 4 levels of delay (1-3, 6, 9, and 12 months), were
      tested for memory for specific laboratory events; children's event-relevant
      verbalizations also were recorded. The children remembered the events that they
      had experienced, regardless of their age at the time of exposure and of the delay
      interval imposed. Memories were demonstrated both nonverbally and verbally;
      nonverbal and verbal measures bore a modest relation with one another. Language
      ability at the time of exposure to the events predicted verbal expression of
      memory after the delay. Thus, the availability of a verbal mode of elaboration
      facilitated 1- to 2-year-olds' event memory.

PMID- 7622990
TI  - What infant memory tells us about infantile amnesia: long-term recall and
      deferred imitation.
AB  - Long-term recall memory was assessed using a nonverbal method requiring subjects
      to reenact a past event from memory (deferred imitation). A large sample of
      infants (N = 192), evenly divided between 14- and 16-months old, was tested
      across two experiments. A delay of 2 months was used in Experiment 1 and a delay
      of 4 months in Experiment 2. In both experiments two treatment groups were used.
      In one treatment group, motor practice (immediate imitation) was allowed before
      the delay was imposed; in the other group, subjects were prevented from motor
      practice before the delay. Age-matched control groups were used to assess the
      spontaneous production of the target acts in the absence of exposure to the model
      in both experiments. The results demonstrated significant deferred imitation for
      both treatment groups at both delay intervals, and moreover showed that infants
      retained and imitated multiple acts. These findings suggest that infants have a
      nonverbal declarative memory system that supports the recall of past events
      across long-term delays. The implications of these findings for the multiple
      memory system debate in cognitive science and neuroscience and for theories of
      infantile amnesia are considered.

PMID- 7622991
TI  - Episodic memory and autonoetic consciousness: developmental evidence and a theory
      of childhood amnesia.
AB  - This research draws together Tulving's (1985) view on episodic memory and
      research on children's developing "theory of mind." Episodic memory, in its
      technical meaning given by Tulving, requires the autonoetic consciousness of
      having experienced remembered events, but developmental findings suggest that
      children cannot encode events as experienced before the age of about 4 or 5
      years. Before this age they have insufficient understanding of what constitutes
      experience, specifically they do not reflect on the perceptual origin of their
      own knowledge. To demonstrate such a link children between 3 and 6 years were
      assessed for their understanding of the perceptual origin of their own knowledge
      on different "see-know tests," in particular a test assessing understanding that
      our senses inform only about certain aspects of the perceived objects. A
      significant association was found between passing see-know tests and free recall,
      which persisted even when cued recall and verbal intelligence are partialed out.
      These results are used to argue that between 3 to 6 years children develop the
      ability to remember events as experienced and that this development can explain
      adults' inability to have recollective experiences of childhood events before
      that age (childhood amnesia).

PMID- 7622992
TI  - Remembering versus knowing the past: children's explicit and implicit memories
      for pictures.
AB  - Two studies are reported examining children's explicit and implicit memory for
      pictures, using measures of recognition memory and perceptual facilitation. In
      Experiment 1, 3-year-olds showed significant implicit memory, as assessed by
      perceptual facilitation in identifying blurred pictures after a 3-month delay,
      even though they showed no explicit memory for the pictures, as assessed by
      recognition. This was true even though initial exposure to the pictures had been
      only in clear focus. The finding was replicated in Experiment 2, which also
      included 5-year-olds and adults. Recognition memory and perceptual facilitation
      were related for adults, but not for children at either age. The data suggest
      that age-related improvements in explicit memory could be due, at least in part,
      to the realization that perceptual fluency can be an indicator of prior
      experience.

PMID- 7622993
TI  - Female reproductive properties and prenatal development of a senescence
      accelerated mouse strain.
AB  - Female reproductive properties, early embryonic development, and serum estradiol
      and progesterone levels of the senescence-accelerated mouse (SAM)-prone (SAM-P)
      strain were compared with those of a SAM-resistant (SAM-R) strain. The
      reproductive life span of SAM-P (from 11.4 to 25.0 weeks old) was shorter than
      that of SAM-R (11.1 to 41.6 weeks old), and the total number of SAM-P pups was
      41.7% less than from SAM-R. The reproductive senescence of SAM-P is more
      accelerated than that of SAM-R. At 15 weeks old, the maximum litter size of SAM-P
      was noted and was 33.7% smaller than that of SAM-R. Although no differences in
      the numbers of ovulated and fertilized ova were observed between two strains, the
      number of implants in SAM-P was 21.6% less than in SAM-R. Cell cleavage was
      delayed in embryos of SAM-P (8% morula, at day 2 of pregnancy) compared to SAM-R
      (48%). At day 3 of pregnancy, 9% and 33% of the embryos were blastocysts in SAM-P
      and SAM-R, respectively. At day 1 of pregnancy, serum estradiol level in SAM-P
      was 18.2% higher than in SAM-R, whereas the serum progesterone level in SAM-P was
      46.2% lower than in SAM-R. The unbalance of estradiol and progesterone levels in
      SAM-P was considered to be the cause of the delay in early embryonic development,
      and then the decrease of implantation and a smaller litter size.

PMID- 7622994
TI  - Monoclonal antibody against a 52 K sperm surface protein inhibits sperm-zona
      pellucida interactions in the rat.
AB  - A major regulatory site for species specificity of fertilization in mammals lies
      at the level of sperm binding to the zona pellucida. This implies a high degree
      of complementarity between gamete and receptor molecules. These molecules support
      species-specific interactions between sperm and oocyte that lead to gamete fusion
      (fertilization). We identified a rat sperm head surface antigen using an IgG1
      monoclonal antibody (HD1) against rat sperm of epididymis cauda. By electron
      microscopy the antigen was shown to be present on the plasma membrane surface of
      the sperm dorsal head. One- and two-dimensional immunoblotting analysis of sperm
      proteins demonstrated that HD1 reacted only with a 52 K molecule with a pI
      ranging from 6.6 to 7.2. The 52 K protein was first detected in situ by indirect
      immunofluorescence and showed to be underlining few elongated spermatids in
      testis. However, when the sperm reached the epididymis caput, the antigen was
      seen to be expressed on the dorsal surface of spermatozoa head. A similar
      fluorescence reaction was detected on sperms in the epididymis corpus and cauda.
      The specific spermatozoa-zona pellucida interaction was inhibited in the presence
      of monoclonal antibody HD1 in a sperm binding assay of in vitro fertilization.

PMID- 7622996
TI  - Analysis of ciliary beat frequencies in hamster oviducal explants.
AB  - We have developed a simple direct method, requiring minimal manipulation, to
      measure beat frequencies of the cilia on the external surface of hamster oviducal
      infundibula in vitro. Two perfusion chambers (closed and open) were used; both
      can be hand-made in a few minutes and discarded after use. Ciliary beat
      frequencies were determined by measuring variations in light intensity with time
      in a single pixel positioned over a video image of the beating cilia. Data files
      were collected using Image 1 software and later transferred to PSI Plot or Lotus
      123 spreadsheets for analysis by counting the number of brightness peaks recorded
      per second or by subjecting the data to Fourier transformation with or without
      smoothing. These methods of analysis gave similar results. To verify that Image 1
      data files contain accurate representations of CBF, videotapes of beating cilia
      were made and subjected to frame-by-frame analysis. Image 1 interfaced with a
      standard video camera was found to collect reliable data over a beat frequency
      range of 0-15 cycles/sec. In some Fourier transforms, secondary peaks were
      observed and were shown to represent cilia beating at more than one frequency in
      a sampled region. Coefficients of variation for repeated measurements taken on
      the same region varied from 4.1% to 9.0%. Small but significant differences were
      found between beat frequencies at different regions of the same oviduct. When
      chambers were perfused discontinuously and measurements of beat frequency were
      made at least 5 min after each perfusion, no effect of perfusion on frequencies
      was observed. However, during continual perfusion of the open chamber, a slight
      but significant increase in beat frequency was observed after perfusion was
      initiated. Muscle contraction, which sometimes occurs in the open chamber, did
      not affect beat frequency measurements. Infundibula could be stored at 4 degrees
      C overnight without any negative effect on beat frequencies. Cold storage also
      reduced muscle contraction. Placement of a small coverslip on infundibula in the
      open chambers was also found to reduce muscle contraction and facilitate beat
      frequency measurements. Coverslipping did not affect beat frequencies. This
      method of beat frequency analysis will be valuable for analyzing factors that
      regulate or influence cilia in mammalian oviducts.

PMID- 7622995
TI  - Immunological detection and characterization of an estrus-associated antigen in
      the goat oviduct.
AB  - The present study was designed to investigate the possibility that the goat
      oviduct produces specific substance(s) similar to the oviductal glycoprotein
      (BOGP) of the bovine oviduct. Oviductal flushings obtained from goats at the
      follicular and luteal phases of the estrous cycle were examined by immunoblotting
      for the presence of material that cross-reacted with monoclonal antibodies (MAbs)
      specific for BOGP. The MAbs immunoreacted with a broad band with a molecular mass
      of protein of about 97 kDa in the flushings of goat oviducts after fractionation
      of proteins by electrophoresis under reducing conditions. The antigen was present
      in flushings obtained from the ampullar segments of oviducts from goats at the
      follicular stage, but this antigen could hardly be detected in the flushings from
      the ampulla at the luteal phase and or the flushings from the isthmus at either
      the follicular or the luteal phase. This antigen was not detected in uterine
      flushings, follicular fluid, or serum. An immunohistochemical study demonstrated
      that the MAbs reacted specifically with the epithelial cells of the goat oviduct.
      Intense labeling was observed in the ampullar and fimbrial epithelia of goat
      oviducts at the follicular phase, but the immunohistochemical reaction was very
      weak at the luteal phase. In the isthmus, the reaction was faint during both the
      follicular and the luteal phase. No specific immunohistochemical reactivity with
      the MAbs was observed with other tissues from the reproductive tract or with
      nonreproductive tissues. Immunofluorescent staining showed that the antigen was
      associated with the zona pellucida of goat ovarian eggs that had been incubated
      with ampullar flushings from goats at the follicular stage.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7622997
TI  - On the c-mos proto-oncogene product during meiotic maturation in bovine oocytes
      cultured in vitro.
AB  - The present study was carried out using dot-blot Western analysis with pp39mos
      specific polyclonal antibodies to examine the quantitative and qualitative
      changes of c-mos proto-oncogene product, Mos, during bovine oocyte maturation in
      vitro. Mos is present throughout meiotic maturation, is produced from around the
      onset of meiotic resumption, and is phosphorylated on germinal vesicle breakdown.
      These results indicate for the first time that the synthesis and phosphorylation
      of Mos during maturation culture play a key role in the accomplishment of meiosis
      in bovine oocytes.

PMID- 7622998
TI  - External and internal influences on indices of physiological stress: II. Seasonal
      and size-related variations in blood composition in free-living lizards,
      Sceloporus occidentalis.
AB  - Seasonal changes in blood composition (plasma osmolality, total plasma protein,
      hematocrit) in two free-living populations of fence lizards, Sceloporus
      occidentalis, one living in a very arid environment (Pearblossom, CA) and another
      in a milder desert (Bend, OR), were analyzed. In this analysis, two features of
      reptilian physiology and ecology were incorporated: ontogenetic variation in
      blood composition and seasonal variation in body-size distribution. The
      population living in the arid environment, but not the mild environment,
      exhibited significant seasonal changes in blood composition: mean plasma
      osmolality increased (345 +/- 4 to 356 +/- 3 mOsmol/kg) and mean plasma protein
      (4.19 +/- 0.20 to 3.34 +/- 0.14 g/dl) and hematocrit decreased (43.8 +/- 0.3 to
      31.6 +/- 0.4) from April to August. These changes suggested that the
      physiological condition of the California population was affected by seasonal
      changes in the external environment. However, among individuals, a significant
      portion of the variation in blood composition was associated with an internal
      factor, body size. Larger lizards had higher osmolality, total protein, and
      hematocrit than smaller lizards in all seasons. In addition, the mean body size
      of active lizards decreased from April to August in California, but not Oregon.
      Because the body-size distribution of active lizards in California shifted
      between seasons, changes in mean population values of these blood parameters
      probably do not accurately reflect changes that occur within individuals and
      therefore may be misleading in assessing the physiological consequences of
      drought.

PMID- 7622999
TI  - Correlation of human papillomavirus 16 and 18 with prognostic factors in invasive
      cervical neoplasias.
AB  - Forty-seven patients with cervical carcinoma were examined in order to correlate
      human papillomavirus (HPV) types with prognostic factors in invasive cervical
      neoplasias. Age, clinical stage, histological type, and grade and parity were
      analysed with respect to HPV status as determined by a general primer mediated
      polymerase chain reaction (PCR) or a type specific PCR. All but one sample (98%)
      harboured HPV sequences: HPV 16 was found in 26 cases (55%), HPV 18 in 19 cases
      (40%), and HPV 31 in 1 case. The presence of HPV 18 DNA was significantly
      associated with cancers developed below 40 years of age (P = 0.029). HPV 18
      detection was associated with poor differentiation malignancy (P = 0.045) and
      histological types of poor prognosis (adenocarcinoma or nondifferentiated
      carcinoma; P = 0.006). HPV 18 positivity was also correlated with advanced
      clinical stages (FIGO II and III; P = 0.032). Parity and HPV status proved to be
      independent of each other (P approximately 0.99). Eighty-seven percent (27/31) of
      pelvic lymph nodes from HPV positive patients contained HPV DNA. The virus types
      found in lymph nodes were identical with those of the primary tumours in all
      cases. Virological results were compared to those obtained by routine
      histological examination. Only 6 of 27 patients with HPV positive lymph nodes had
      any histological evidence of metastasis. Nevertheless, the lack of metastasis as
      detected by histology does not exclude the possibility of relapses. Follow-up of
      the clinical prognostic significance of PCR detection of HPV in the possible
      sites of early metastases.

PMID- 7623000
TI  - Circulating immune complexes in chronic hepatitis C.
AB  - For assessing the role of circulating immune complexes (CIC) in chronic hepatitis
      C, the relative frequency of CIC was determined in 54 patients with chronic
      hepatitis C, 15 asymptomatic hepatitis C virus (HCV) carriers, and 54 healthy
      controls. IgM and IgG containing CIC were studied using both C1q and conglutinin
      (K) in an immunoglobulin-specific solid-phase enzyme immunoassay. CIC were a
      common feature of chronic hepatitis C with 96.3% of patients with at least one
      abnormal test result. The prevalence of elevated IgG-K, IgM-K, IgG-C1q, and IgM
      C1q CIC was 70.3%, 50.0%, 64.8%, and 35.1%, respectively. The prevalence of IgG
      class CIC was higher than IgM class CIC (P = 0.038 for K-CIC and P = 0.01 for C1q
      CIC, respectively). There is correlation between IgG-K CIC and IgG-C1q CIC (r =
      0.445, P = 0.002), IgG-K CIC and IgM-C1q CIC (r = 0.348, P = 0.020), IgM-K CIC
      and aspartic aminotransferase (r = 0.321, P = 0.015), IgM-K CIC and alanine
      aminotransferase (r = 0.301, P = 0.027). Compared to patients with chronic
      persistent hepatitis and chronic lobular hepatitis, patients with chronic active
      hepatitis have a higher prevalence of elevated IgG-K CIC (77.2% vs. 40.0%, P =
      0.029) and IgM-K CIC (56.8% vs. 20.0%, P = 0.038). The concentration of IgG-K,
      IgM-K, and IgM-C1q CIC in the former was significantly higher than that in the
      latter, respectively. In conclusion, IgG class CIC is the major type of CIC in
      chronic hepatitis C.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7623001
TI  - HIV-1 infection in Juba, southern Sudan.
AB  - Thirty years of civil war in the Sudan have resulted in the isolation of the
      southern provinces which border Central and East Africa. Consequently, little is
      known about the epidemiology of HIV-1 infection in this region. To estimate the
      prevalence of HIV-1 infection in southern Sudan and the risk factors associated
      with disease transmission, a seroepidemiologic survey was conducted in the
      township of Juba. Study subjects invited to participate in this study included
      medical outpatients, inpatients hospitalized for active tuberculosis, and female
      prostitutes. A total of 401 subjects participated in the study. HIV-1 infection
      was confirmed in 25 subjects. The prevalence of HIV-1 infection was 19% (8/42)
      among tuberculosis patients, 16% (8/50) among prostitutes, and 3% (9/309) among
      outpatients. A significantly higher prevalence of HIV-1 infection was found among
      female prostitutes when compared to female outpatients: 16% (8/50) vs. 2%
      (4/178), P < 0.001. Correspondingly, the prevalence of seropositives was
      significantly higher among male outpatients reporting a history of sexual
      relations with prostitutes during the prior 10 years compared to male outpatients
      denying relations with prostitutes: 14% (5/37) vs. 0% (0/94), P = 0.0011. A
      history of a sexually transmitted disease (STD) was also associated with HIV-1
      infection among male outpatients. The findings of this study indicate that HIV-1
      infection is highly prevalent in southern Sudan and that prostitutes and their
      sexual partners represent a major reservoir of HIV infection in this population.
      This epidemiologic pattern resembles that seen in the African nations neighboring
      southern Sudan.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7623002
TI  - Phylogenetically distinct hantavirus implicated in a case of hantavirus pulmonary
      syndrome in the northeastern United States.
AB  - Hantavirus pulmonary syndrome (HPS) is an acute respiratory illness with high
      mortality. It is caused by a newly described New World hantavirus known as Four
      Corners virus (FCV). Nearly all cases of HPS have occurred in the western United
      States. The etiologic agents in those cases have been closely related to each
      other, based upon comparisons of their genetic sequences. We have molecularly
      cloned the S genomic segment of a hantavirus (Rl-1) implicated in a case on HPS
      in the northeastern United States. Nucleotide sequence analysis shows that the Rl
      1 virus has many similarities to FCV, but is clearly distinct from the western
      forms of that virus. These data suggest that HPS can be caused by multiple agents
      that together form a distinctive evolutionary clade.

PMID- 7623003
TI  - Efficacy of kakkon-to, a traditional herb medicine, in herpes simplex virus type
      1 infection in mice.
AB  - Kakkon-to is one of the representative traditional herb medicines (Kampo
      formulae) and has been used historically for the treatment of infectious diseases
      in China and Japan. The efficacy of this preparation was characterised using a
      cutaneous herpes simplex virus type 1 (HSV-1) infection in mice as a model for
      human viral infection. Kakkon-to at a dose corresponding to human use reduced
      significantly the mortality of HSV-1-infected mice and localised skin lesions.
      Delayed type hypersensitivity (DTH) response to HSV-1 antigen was significantly
      stronger in treated mice than in untreated mice. However, no histopathological
      difference was noted in the skin lesions between treated and untreated mice
      except for the size of the lesions. Kakkon-to did not inhibit the growth of HSV-1
      in vitro. Natural killer cell activity, natural cytotoxic killer cell activity,
      and the population of T-cell subsets in spleen cells of infected mice were not
      affected by the drug. Kakkon-to did not augment interferon induction and anti-HSV
      1 antibody production, nor increased cytokine levels such as interleukin-1 alpha,
      interleukin-2, interferon-gamma, and tumour necrosis factor-alpha in sera of
      infected mice. Thus, Kakkon-to induced strong DTH to HSV-1 in infected mice,
      which may have caused localisation of skin lesions and reduction in the mortality
      of treated mice.

PMID- 7623004
TI  - Isolation of black creek canal virus, a new hantavirus from Sigmodon hispidus in
      Florida.
AB  - Numerous rodents were trapped for serologic and virologic studies following the
      identification of a hantavirus pulmonary syndrome (HPS) case in Dade County,
      Florida. Cotton rats (Sigmodon hispidus) were the most frequently capture rodent
      and displayed the highest seroprevalence to a variety of hantavirus antigens.
      Hantavirus genome RNA was detected in all the seropositive cotton rats tested,
      using a reverse transcriptase-polymerase chain reaction (RT-PCR) assay. A virus
      was isolated from tissues of two seropositive cotton rats by cultivation of lung
      and spleen homogenates on Vero E6 cells. Nucleotide sequence information obtained
      by direct RT-PCR and the serologic relationships of this virus with the other
      hantaviruses indicate that this virus, Black Creek Canal virus, represents a new
      hantavirus distinct from the previously known serotypes.

PMID- 7623005
TI  - Immunogenicity and safety of an inactivated hepatitis A vaccine in anti-HIV
      positive and negative homosexual men.
AB  - The immunogenicity, reactogenicity, and safety of an inactivated hepatitis A
      vaccine were assessed in anti-HIV positive homosexual men. Fourteen anti-HIV
      positive (group 1) and 20 anti-HIV negative (group 2) men received vaccine
      (containing 720 ELISA units of hepatitis A antigen per dose) intramuscularly at
      0, 1, and 6 months. Twelve unvaccinated anti-HIV positive men (group 3) were
      included as controls to evaluate disease progression. Seroconversion (anti
      hepatitis V virus (HAV) > or = 20 mlU/ml) was higher in group 2 than group 1 at
      months 2 (100% vs. 73%) and 7 (100% vs. 77%). Group 2 had higher antibody titres
      than group 1 at months 1 (201 vs. 92 mlU/ml) and 7 (1,687 vs. 636 mlU/ml). The
      decline in CD4+ cells between months 0 and 7 was similar in groups 1 and 3 (6.4%
      vs. 16.2%), showing no evidence for harmful effect of the vaccine on the course
      of HIV infection. This hepatitis A vaccine appears safe, well tolerated, but less
      immunogenic in HIV positive homosexual men.

PMID- 7623006
TI  - Combined treatment with interferon alpha-2b and ribavirin for chronic hepatitis C
      in patients with a previous non-response or non-sustained response to interferon
      alone.
AB  - Ten patients with chronic hepatitis C, six of whom had not responded and four of
      whom had responded in a non-sustained fashion to interferon-alpha treatment
      alone, were given interferon alpha-2b and ribavirin in combination during 24
      weeks. Interferon alpha-2b was given subcutaneously, at a dose of 3 MU thrice
      weekly, together with ribavirin orally, at a dose of 1,000-1,200 mg/day. All four
      patients with a prior non-sustained response to interferon alone had normal
      alanine aminotransferase (ALT) levels at the end of treatment as well as during
      follow-up (> or = 24 weeks post treatment). Furthermore, all four lost serum HCV
      RNA at the end of treatment and three continued to be negative during follow-up.
      Among patients with a prior non-response to interferon alone three of six had
      normal ALT levels at the end of treatment and one at follow-up. Two of six became
      HCV-RNA negative at cessation of treatment, one of whom was negative also at
      follow-up. All former non-sustained responders and one of six non-responder
      patients thus showed a sustained biochemical response with eradication of HCV-RNA
      from serum in all cases but one. It is concluded that combination therapy with
      interferon alpha-2b and ribavirin offers a chance of sustained biochemical
      response with eradication of the viremia in patients who have not shown a
      persistent response to interferon-alpha alone.

PMID- 7623007
TI  - Detection of human herpesvirus 6 DNAs in samples from several body sites of
      patients with exanthem subitum and their mothers by polymerase chain reaction
      assay.
AB  - Polymerase chain reaction amplification was used to detect human herpesvirus 6
      (HHV-6) DNAs in peripheral blood mononuclear cells (MNCs), plasma, saliva, stool,
      and urine from three patients with exanthem subitum and in peripheral blood MNCs,
      plasma, and saliva from their mothers. HHV-6 DNAs were detected in MNCs during
      and after the disease and were found in plasma only in the acute phase. The virus
      DNAs were also detected in saliva after recovery from the illness and were found
      persistently or intermittently in stool but not in urine samples after the onset
      of the disease. In contrast, one of the three mothers excreted HHV-6 DNAs
      persistently in saliva. None of the mothers had the virus DNAs in peripheral
      blood MNCs and plasma nor a significant increase in antibody titers to HHV-6
      after possible exposure from their children. These findings suggest systemic
      replication of HHV-6 during the acute phase in patients with exanthem subitum and
      persistent infection of the virus in several organs after recovery from the
      disease.

PMID- 7623008
TI  - Prevalence of antibodies against hepatitis A virus among new immigrants in
      Israel.
AB  - Israel, located in a region endemic for hepatitis A virus (HAV), recently
      absorbed a large population of immigrants who came from the former USSR. To
      assess the risk of high morbidity in this population a serosurvey of HAV
      antibodies was undertaken. Serum samples were collected from 965 new immigrants,
      of whom 664 came from the European, non-endemic region, and 301 from the Asian
      and Caucasian endemic regions of the former Soviet Union. They were compared to
      240 Israelis. Each population was divided into six age groups: 1-9, 10-19, 20-29,
      30-39, 40-49, and 50 years of age and older. The Asian/Caucasian immigrants and
      the Israeli population were found to share similar characteristics. In both
      groups, antibodies to HAV (anti-HAV) were present in the 1-9-year-old age group
      and reached maximum prevalence (90% and 86.7%, respectively) in the 20-29-year
      old age group. In contrast, among the European immigrants anti-HAV was first
      found in the 10-19-year-olds and peaked (93%) in the age group of 50 years and
      older. It is concluded that immigrants originating from the European part of the
      former USSR may require vaccination against hepatitis A.

PMID- 7623009
TI  - Measurement by the polymerase chain reaction of the Epstein-Barr virus load in
      infectious mononucleosis and AIDS-related non-Hodgkin's lymphomas.
AB  - A polymerase chain reaction (PCR) assay for the detection of Epstein-Barr virus
      (EBV) sequences in various clinical samples, especially peripheral blood
      leukocytes (PBL) and serum, was carried out and the results obtained were
      compared with specific EBV serology. One hundred seventy patients were enrolled
      in the study: 89 healthy blood donors, 22 asymptomatic patients, 36 individuals
      with primary EBV infection (including 19 patients with infectious mononucleosis
      [IM]), 22 HIV-infected subjects (including 4 with hairy oral leukoplakia, 3 with
      central nervous disorders, and 15 with non-Hodgkin's lymphoma). All the serum
      samples from the healthy blood donors were negative. In patients with IM and in
      AIDS-non Hodgkin's lymphoma (ARNHL), PCR was strongly positive in leukocytes (>
      2,000 genome equivalents/10(4) cells), which was correlated with detectable
      amounts of EBV DNA in serum. The overall positivity rate of PCR in serum was
      58.8%, 68%, and 73% of cases for non-IM primary EBV infections, IM, and ARNHL,
      respectively. In two cases of EBV primary infection, the viral DNA was detected
      in serum, respectively 1 month and 2 months before IgM positivity and IgG rise.
      In one case of ARNHL followed up for several months, PCR (viral load of 2,000
      genome equivalents/10(4) cells) became positive concurrently with appearance of
      lymphoma. In immunocompromised individuals, PCR EBV, if carried out in larger
      prospective studies, could be considered as a tumor marker, useful for predicting
      EBV-driven lymphoma and follow-up therapy.

PMID- 7623010
TI  - Comparison of the hypervariable region of hepatitis C virus genomes in plasma and
      liver.
AB  - Nucleotide sequences of the hypervariable region of hepatitis C virus genomes
      obtained from plasma change rapidly during the course of infection and are
      believed to play a part in immunological escape and consequently in the
      development of persistent infection. It is not known, however, whether these
      changes also occur in the liver. To clarify this aspect, RNA was extracted from
      the plasma and liver tissue of eight patients with chronic hepatitis C. After
      cDNA synthesis, DNA fragments that included the hypervariable region were
      amplified by the polymerase chain reaction. Consensus nucleotide sequences were
      determined directly from the polymerase chain reaction products by the dideoxy
      chain termination method. The diversity of the hypervariable region was analyzed
      further by the polymerase chain reaction-single strand conformation polymorphism
      analysis. Consensus nucleotide sequences of the hypervariable region were
      identical between the plasma and the liver in each patient. The polymerase chain
      reaction-single strand conformation polymorphism analysis showed multiple DNA
      bands that represented different hypervariable region sequences. Comparison of
      the single strand conformation polymorphism patterns revealed that the number,
      the mobility, and the density of bands were the same between the plasma and the
      liver. It is concluded that the population and the diversity of hepatitis C virus
      quasispecies as detected by the hypervariable region sequence are the same
      between the plasma and the liver despite rapid mutations, indicating that rapid
      changes in the population of hepatitis C virus quasispecies also occur in the
      liver.

PMID- 7623011
TI  - Herpes simplex virus DNA in normal corneas: persistence without viral shedding
      from ganglia.
AB  - Herpes simplex virus type 1 (HSV-1) DNA has been shown to persist in the cornea
      not only after inoculation of experimental animals but also in surgical samples
      from patients with herpes keratitis. The further observation of corneal HSV-1 DNA
      in subjects without known HSV eye disease prompted the present study of the
      presence and distribution of HSV-1 in eye bank corneas. Prior to DNA extraction,
      the corneas were trephined, separating the central and peripheral cornea. With
      polymerase chain reaction (PCR) for HSV-1 thymidine kinase (TK) and glycoprotein
      D (gD) gene sequences, we found HSV-1 in 10 of 24 eye bank corneas, from the 4 mm
      wide corneal rim in 8 eyes and from the 8 mm diameter central cornea in 2 eyes.
      In 9 subjects, both eyes were assayed, and HSV-1 was detected in 6 subjects. In
      only one subject was HSV-1 detected in both eyes and in only one subject was HSV
      1 detected in the central and peripheral cornea of the same eye. The biological
      role of HSV-1 DNA corneal sequences is unknown. To investigate this, a rabbit
      animal model was established by transplantation of corneas containing viral DNA
      sequences in HSV-1 naive recipients. Followed for 5 months, there was no evidence
      of sheeding of HSV-1 in the tear film or seroconversion of the recipient rabbits.
      At the end of this time, HSV-1 DNA was detected in the corneal graft at a similar
      intensity to the PCR signal from the donor rims.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7623012
TI  - Molecular and serologic analysis in the transmission of the GB hepatitis agents.
AB  - Two flavivirus-like genomes have recently been cloned from infectious tamarin
      (Saguinus labiatus) serum, derived from the human viral hepatitis GB strain,
      which is known to induce hepatitis in tamarins. In order to study the natural
      history of GB infections, further transmission studies were carried out in
      tamarins. Reverse-transcription-polymerase chain reaction and enzyme-linked
      immunosorbant assays were developed for the detection of RNA and antibodies
      associated with the two agents, GB virus-A and GB virus-B. The infectivity of
      both of these agents was demonstrated in tamarins to be filterable through a 0.1
      micron filter. Two distinct genomes were identified in the serum of eight of the
      infected tamarins, while in four tamarins, the genomes were detected
      independently of each other. Although specific antibodies to the GB virus-B
      epitopes were detected in the serum of animals inoculated with both agents or GB
      virus-B alone, antibodies to putative epitopes specific to GB virus-A were not
      detected in any of the animals. All tamarins inoculated with serum containing GB
      virus-B exhibited an elevation in liver enzyme levels after inoculation.
      Elevations of serum liver enzyme levels did not occur when GB virus-A was the
      only agent detected in the serum. Infection with the original infectious tamarin
      inoculum conferred protection from reinfection with GB virus-B but not with GB
      virus-A.

PMID- 7623013
TI  - Investing in mental health research.

PMID- 7623014
TI  - Psychache in context:states'spending for public welfare and their suicide rates.
AB  - This analysis draws together the concept of psychache that describes the
      psychological pain associated with suicide and Durkheim's social integration
      theory in analyzing the relationship between states' spending for public welfare
      and their suicide rates over a 30-year period, from 1960, 1970, 1980, 1985, and
      1990. Given that the threshold for enduring psychological pain varies from person
      to person, the questions were: Does suicide also vary with social context and has
      this changed over time? The answer to both questions was yes. Whereas the
      prevalence of divorce in combination with low population density and high rates
      of population change provided the context for interstate differences in suicide
      rates over the entire observational period and accounted for their increased
      variability in 1970 and 1980, this was not the case in 1985 or 1990. In both 1985
      and 1990, the two variables that were important in this regard were states'
      spending for public welfare and race. In 1990, not only were suicide rates higher
      in states that spent less for public welfare than in states that spent more, but
      states' spending for public welfare was the only variable that accounted for the
      widening of differences in states' suicide rates. Given the strong prevailing
      skepticism that government can help solve people's problems and widespread
      antagonism toward government social spending, these findings carry an important
      message.

PMID- 7623015
TI  - Religious or spiritual problem. A culturally sensitive diagnostic category in the
      DSM-IV.
AB  - A new diagnostic category entitled religious or spiritual problem has been
      included in the fourth edition of the Diagnostic and Statistical Manual of Mental
      Disorders (DSM-IV) under Other Conditions That May Be a Focus of Clinical
      Attention. Along with several other changes, this category contributes
      significantly to the greater cultural sensitivity incorporated into DSM-IV. The
      authors review the approval process, including the changes that were made in both
      the proposed new category and the former V Code section of DSM-III-R. In
      addition, the definition, assessment methods, types, and clinical significance of
      religious and spiritual problems are clarified, along with the differential
      diagnostic issues raised by the definitional changes in the former V Code
      section. Finally, clinical issues involving cultural sensitivity and the
      implications for future research are addressed. The new category could help to
      promote a new relationship between psychiatry and the fields of religion and
      spirituality that will benefit both mental health professionals and those who
      seek their assistance.

PMID- 7623017
TI  - Involuntary memories during severe physical illness or injury.
AB  - This paper reports an analysis of the features of 122 cases of persons who became
      ill or even came close to death, but who survived and afterward reported that
      during the experience they recalled memories of earlier events in their lives.
      The life review varied widely in its form; the number of memories recalled ranged
      from only one or two to the subject's entire life. Moreover, few of the subjects
      reported seeing earlier events of their life "all at once," which makes the
      popular phrase "panoramic memory" a misnomer. One group of 54 cases was compared
      with a group of 54 other cases in which the feature of the life review did not
      occur. There were no significant differences between the two groups with regard
      to nine common features. The life review occurs as one feature among several
      others of equal or greater importance in the total experience. Its function, if
      any, remains to be elucidated by further research.

PMID- 7623016
TI  - Personality and abilities of children claiming previous-life memories.
AB  - Young children who claim memories of a previous life can be found in many
      countries, particularly in Asia. The child frequently states where he/she lived
      previously, often claims violent death in the previous life and shows
      phobias/philias, and sometimes has birthmarks or deformities that he/she
      associates with the previous life. The Gudjonsson Suggestibility Scale, Raven
      Progressive Matrices, Peabody Picture Vocabulary Test, and the Child Behavior
      Checklist were administered to 23 children in Sri Lanka who, mostly at an earlier
      age, had consistently been claiming memories of a previous life. They had greater
      verbal skills and better memory than their peers, performed much better in
      school, and were more socially active, but were not more suggestible. As judged
      by their parents, they had a higher Child Behavior Checklist problem score than
      their peers, but not according to their teachers.

PMID- 7623018
TI  - Association with companion animals and the expression of noncognitive symptoms in
      Alzheimer's patients.
AB  - Interactions with companion animals have been shown to have socializing and
      calming effects for Alzheimer's patients in an institutional setting. Sixty-four
      Alzheimer's patients living in the private home were studied, through medical
      records and information provided by caregivers, to determine what effect
      association with a companion animal had on the progression of cognitive decline
      and the manifestation of concomitant noncognitive symptoms. Prevalence of
      episodes of verbal aggression and anxiety was reported less frequently in 34
      patients who were exposed to companion animals compared with patients who were
      not exposed. Significantly fewer mood disorders were reported in patients who
      were attached to their pets compared with patients who were not attached. There
      was no significant difference in the rate of cognitive decline between pet
      exposed and nonexposed patients as measured by three standard indices. This study
      lends preliminary support to the belief that interaction with pets can aid in
      tempering feelings of agitation and aggression in Alzheimer's patients.

PMID- 7623019
TI  - Lack of insight in bipolar disorder. The acute manic episode.
AB  - This study examined the clinical correlates of lack of insight in bipolar
      disorder. In 28 acutely manic patients interviewed upon hospitalization and/or
      discharge, mean scores on the Insight and Treatment Attitudes Questionnaire
      (ITAQ) improved only slightly, from 12.0 on admission to 15.5 on discharge (p =
      .08), despite marked improvement in other psychiatric symptoms. A reciprocal
      relationship was found between higher ITAQ scores and involuntary hospitalization
      (r = -.38). Like schizophrenia, bipolar disorder appears to be a condition in
      which poor insight is a prominent characteristic.

PMID- 7623020
TI  - Level of functioning, severity of illness, and smoking status among chronic
      psychiatric patients.
AB  - It was hypothesized that chronic psychiatric patients who had quit smoking would
      be more functional and have lower Brief Psychiatric Rating Scale (BPRS) scores
      than those who continued to smoke. We interviewed 300 chronic psychiatric
      patients followed in the community. Fourteen percent were former smokers and
      nearly 11% had never smoked. Fifty-six percent of the sample were current smokers
      who had no intention of quitting, 13% were considering quitting, and 6% were
      seriously preparing to quit or had actually quit for a short period. When
      compared with current smokers, former smokers were more likely to live
      independently (p < .026) and less likely to have a drug or alcohol problem (p <
      .013). A random sample of current smokers were compared with former smokers on
      the BPRS. Former smokers had lower total BPRS scores (p < .03), and lower
      withdrawal/retardation subscale scores (p < .0058) than current smokers. We
      concluded that better functioning patients who smoked would be more likely to
      quit.

PMID- 7623021
TI  - Self-analysis: structure, extension, and computerization.
AB  - In this article, a structure for self-analysis is described and the expanded
      applicability of self-analysis implied by the suggested structure is examined.
      Also, the stage of computer psychotherapy programs is reviewed, and an overview
      of a plan for merging self-analysis and computer psychotherapy is presented.

PMID- 7623022
TI  - Meta-analysis of randomized controlled trials of cranial electrostimulation.
      Efficacy in treating selected psychological and physiological conditions.
AB  - To clarify the diverse published results of cranial electrostimulation (CES)
      efficacy, we conducted an extensive literature review that identified 18 of the
      most carefully conducted randomized controlled trials of CES versus sham
      treatment. For the 14 trials that had sufficient data, we used the techniques of
      meta-analysis to pool the published results of treating each of four conditions:
      anxiety (eight trials), brain dysfunction (two trials), headache (two trials),
      and insomnia (two trials). Because studies utilized different outcome measures,
      we used an effect size method to normalize measures which we then pooled across
      studies within each condition. The meta-analysis of anxiety showed CES to be
      significantly more effective than sham treatment (p < .05). Pooling did not
      affect results that were individually positive (headache and pain under
      anesthesia) or negative (brain dysfunction and insomnia). Most studies failed to
      report all data necessary for meta-analysis. Moreover, in all but two trials, the
      therapist was not blinded and knew which patients were receiving CES or sham
      treatment. We strongly recommend that future trials of CES report complete data
      and incorporate therapist blinding to avoid possible bias.

PMID- 7623023
TI  - Depression, interpersonal style, and communication skills.

PMID- 7623024
TI  - Computerized assessment of depression and suicidal ideation.

PMID- 7623025
TI  - Antitumor agents, 154. Cytotoxic and antimitotic flavonols from Polanisia
      dodecandra.
AB  - Three flavonols, 5,3'-dihydroxy-3,6,7,8,4'-pentamethoxyflavone [1], 5,4'
      dihydroxy-3,6,7,8,3'-pentamethoxyflavone [2], and quercetin 3-O-beta-D
      glucopyranosyl-7-O-alpha-L-rhamnopyranoside [3], were isolated from Polanisia
      dodecandra. Compound 1 showed remarkable cytotoxicity in vitro against panels of
      central nervous system cancer (SF-268, SF-539, SNB-75, U-251), non-small cell
      lung cancer (HOP-62, NCI-H266, NCI-H460, NCI-H522), small cell lung cancer (DMS
      114), ovarian cancer (OVCAR-3, SK-OV-3), colon cancer (HCT-116), renal cancer (UO
      31), a melanoma cell line (SK-MEL-5), and two leukemia cell lines (HL-60 [TB],
      SR), with GI50 values in the low micromolar to nanomolar concentration range.
      This substance also inhibited rubulin polymerization (IC50 = 0.83 +/- 0.2 microM)
      and the binding of radiolabeled colchicine to tubulin with 59% inhibition when
      present in equimolar concentrations with colchicine. Compound 2 also showed
      cytotoxicity against medulloblastoma (TE-671) tumor cells with an ED50 value of
      0.98 microgram/ml. Compound 1 appears to be the first example of a flavonol to
      exhibit potent inhibition of tubulin polymerization and, therefore, warrants
      further investigation as an antimitotic agent.

PMID- 7623026
TI  - Adoligoses, oligosaccharides of rare sugars from Adonis aleppica.
AB  - Five novel tri-, tetra-, and penta-saccharides named adoligoses A-E [1-5],
      consisting of rare didesoxy sugars and their 3-O-Me ethers, have been isolated
      from Adonis aleppica. Their structures were determined by dcims and nmr
      measurements. Full establishment of the proton spin-systems was based on 2D nmr
      data, spectral simulation procedures, and force-field calculations. Sarmentose
      and cymarose moieties were found in both anomeric configurations and represent a
      major difference from alepposides A-D, biogenetically related cardenolide
      oligoglycosides isolated previously from the same plant source. This is the first
      report on complex, long-chained oligosaccharides of 2,6-didesoxy sugars found
      typically in cardenolide and pregnane glycosides.

PMID- 7623027
TI  - Antitumor agents, 157. Absolute structures of cumingianosides A-F, antileukemic
      triterpene glucosides, and structures of the hydrolysates of cumingianoside A.
AB  - The stereostructures of cumingianosides A-F, a series of triterpene glucosides
      with a 14,18-cycloapoeuphane skeleton, have been established by X-ray
      crystallographic analysis on an aglycone [1c] the acid hydrolysate of
      cumingianoside A [1], which is a potent cytotoxic triterpene against MOLT-4 human
      leukemia cells with an EC50 value of < 0.00625 microM. The 14,18-cyclopropane
      ring in cumingianoside A [1] was opened under acidic conditions in two different
      directions to give compounds with an apoeuphane skeleton and a dammarane
      skeleton. Furthermore, it was found that subsequent hydrolysis yielded not only
      an aglycone with an apoeuphane skeleton [1c] but also an apo-rearrangement
      product [1d].

PMID- 7623028
TI  - New cyclopeptide alkaloids from Ziziphus lotus.

PMID- 7623029
TI  - New dammarane-type glycosides from Gynostemma pentaphyllum.
AB  - Four novel dammarane glycosides were isolated from a MeOH extract of the aerial
      parts of Gynostemma pentaphyllum. Their structures were elucidated by 1D and 2D
      nmr experiments, including 1H-1H correlation spectroscopy (COSY, HOHAHA, NOESY)
      and 1H-13C heteronuclear correlation (HETCOR). The aglycone moieties are the new
      dammarane-type triterpenes (20S)-3 beta,20,23 xi-trihydroxydammar-24-en-21-oic
      acid-21,23-lactone for 1, the corresponding epimer at C-20(20R) for 2, (20S)
      dammar-23-ene-3 beta-20,25,26- tetraol for 3, and (20R)-dammar-25-ene-3
      beta,20,21,24 xi-tetraol for 4.

PMID- 7623030
TI  - The novel desmethyldestruxin B2, from Metarhizium anisopliae, that suppresses
      hepatitis B virus surface antigen production in human hepatoma cells.
AB  - We have examined the antiviral activity of a crude extract prepared from the
      culture medium of the fungus Metarhizium anisopliae. Eight active destruxins were
      identified which showed strong suppressive effect on the production of the
      hepatitis B surface antigen (HBsAg) in human hepatoma Hep3B cells. One new
      compound, desmethyldestruxin B2 [1], was isolated from M. anisopliae. This
      structure was determined based on its nmr and mass spectral data.

PMID- 7623031
TI  - Venezenin: a new bioactive Annonaceous acetogenin from the bark of Xylopia
      aromatica.
AB  - Asimicin and a new cytotoxic Annonaceous acetogenin, venezenin [1], were isolated
      from the bark of Xylopia aromatica by bioactivity-directed fractionation using
      lethality to brine shrimp. Compound 1 represents an unusual type of C37
      Annonaceous acetogenin, lacking either tetrahydrofuran (THF) or epoxide rings and
      possessing a double bond located two methylenes away from a vicinal diol in the
      hydrocarbon chain. The structure of 1 was elucidated by 1H- and 13C-nmr, COSY,
      single-relayed COSY, and by HMBC techniques, and derivatization. Annomontacin 10
      one [6] and 18/21-cis-annomontacin-10-one [7], two semi-synthetic mono-THF
      acetogenins were prepared from 1. These acetogenins showed cytotoxicity,
      comparable or superior to adriamycin, against three human solid tumor cell lines.
      Reduction of the 10-keto of 1 to the racemic OH-10 derivative enhanced the
      bioactivity, as did the conversion of 1 to 6 and 7. Venezenin [1], like other
      Annonaceous acetogenins, showed inhibition of oxygen uptake by rat liver
      mitochondria and demonstrated that the THF ring may not be essential to this mode
      of action.

PMID- 7623033
TI  - Four cyclopeptide alkaloids from Discaria longispina.
AB  - The isolation of the cyclopeptide alkaloids, adoutine-Y', discarine-B, discarine
      E, and discarine-X, a new 14-membered cyclopeptide alkaloid from D. longispina,
      are reported. The structure of the new alkaloid was elucidated by spectroscopic
      methods and by chemical degradation.

PMID- 7623032
TI  - The isolation and structural elucidation of three new neolignans, piperulins
      [corrected] A, B, and C, as platelet activating factor receptor antagonists from
      Piper puberulum.
AB  - Three new neolignans, piperulins [corrected] A [1], B [2], and C [3], were
      isolated from Piper puberulum. Their structures and relative stereochemistries
      were determined from spectral data and the X-ray crystallographic analysis of 1.
      Compounds 1 and 3 inhibit specific platelet activating factor receptor binding
      with IC50 values of 7.3 and 5.7 microM, respectively.

PMID- 7623034
TI  - Brevitaxin, a new diterpenolignan from the bark of Taxus brevifolia.
AB  - The first terpenolignan, brevitaxin [1], has been isolated from the bark of Taxus
      brevifolia. Identification was carried out using spectral methods, and the
      regiochemistry and cytotoxicity of 1 are discussed.

PMID- 7623035
TI  - Isolation of a cyclic carbonate, a gamma-butyrolactone, and a new indole
      derivative from the marine cyanobacterium Lyngbya majuscula.

PMID- 7623036
TI  - Three new omega-cycloheptyl fatty acids from Alicyclobacillus cycloheptanicus and
      their biosynthetic interrelationships.
AB  - Three minor omega-cycloheptyl fatty acids from Alicyclobacillus cycloheptanicus
      have been identified as omega-cycloheptylnonanoate, -decanoate, and -alpha
      hydroxytridecanoate. The biosynthetic interrelations of these cyclic fatty acids
      have been studied. 13C-Labeled omega-cycloheptylundecanoate and -alpha
      hydroxyundecanoate were converted to omega-cycloheptyldecanoate, which is one
      carbon shorter in length. alpha-Hydroxylation of omega-cycloheptylundecanate was
      also observed, but not chain extension to omega-cycloheptyltridecanoate.

PMID- 7623037
TI  - Patellamide F, A new cytotoxic cyclic peptide from the colonial ascidian
      Lissoclinum patella.
AB  - Cytotoxicity-directed fractionation of an organic extract of the tunicate
      Lissoclinum patella afforded a new cyclic octapeptide, patellamide F [1]. The
      structure and absolute stereochemistry of 1 were established by a combination of
      spectroscopic and chemical methods. Three known cyclic peptides, patellamide B
      [2], ulithiacyclamide, and lissoclinamide 3, were also isolated and identified.

PMID- 7623038
TI  - (-)-Roemerine, an aporphine alkaloid from Annona senegalensis that reverses the
      multidrug-resistance phenotype with cultured cells.
AB  - A known aporphine alkaloid, (-)-roemerine [1], isolated from the leaves of Annona
      senegalensis, was found to enhance the cytotoxic response mediated by vinblastine
      with multidrug-resistant KB-V1 cells. In the absence of vinblastine, no
      significant cytotoxicity was observed with KB-3 or KB-V1 cells (ED50 > 20
      micrograms/ml), and several other human tumor cell lines were also relatively
      insensitive. As indicated by its ability to inhibit ATP-dependent [3H]vinblastine
      binding to multidrug-resistant KB-V1 cell membrane vesicles, (-)-roemerine
      appears to function by interacting with P-glycoprotein. In addition to alkaloid
      1, three inactive compounds [the aporphine alkaloid(-)-isocorydine (reported in
      the levo-configuration for the first time), and the lignans (+/-)-8,8'
      bisdihydrosiringenin [2] (a new natural product), and (+)-syringaresinol] were
      also isolated.

PMID- 7623039
TI  - The cyclorenierins, sesquiterpenoid quinols from the sponge Haliclona sp.
      collected in Vanuatu.
AB  - Two sesquiterpene quinols, cyclorenierins A [1] and B [2], which are closely
      related to panicein A2 [3] and renierin A [4], were isolated as an inseparable
      mixture from the marine sponge Haliclona sp. collected in Vanuatu. Structures
      were proposed using nmr shift analogies to 3 and 4 and confirmed with 2D nmr
      data.

PMID- 7623041
TI  - 3 beta-aminospirosolane steroidal alkaloids from Solanum triste.
AB  - The alkaloid fraction of the MeOH extract of the aerial parts of Solanum triste
      afforded the new steroidal alkaloid, (22R,25R)-3 beta-amino-5-spirosolene [2],
      and its previously synthesized dihydro derivative, (22R,24R)-3 beta-amino-5 alpha
      spirosolane [3], which is reported here for the first time as a natural product.
      The structures were elucidated by spectral techniques including 1H-nmr, 13C-nmr,
      and 1H-1H COSY, HMQC, HMBC, and NOESY nmr experiments.

PMID- 7623040
TI  - Gamma-indomycinone, a new pluramycin metabolite from a deep-sea derived
      actinomycete.
AB  - A new member of the pluramycin class of antibiotics, gamma-indomycinone [1], has
      been isolated along with the known compounds rubiflavinone C-1 [2] and beta
      indomycinone [3] from the culture broth of a Streptomyces sp. obtained from a
      deep-sea sediment core. Each compound is composed of an anthraquinone-gamma
      pyrone nucleus, but bears a different side-chain. Compounds 2 and 3 were
      identified by comparison of their spectral data with published data, while gamma
      indomycinone [1] was characterized using 1H-nmr and mass spectrometry.

PMID- 7623042
TI  - Dihydrolicoisoflavone, a new isoflavanone from Swartzia polyphylla.
AB  - Fractionation of an ethanolic extract of Swartzia polyphylla, guided in part by
      an assay for inhibition of protein kinase C, led to the isolation of the known
      flavonoids biochanin A, dihydrobiochanin A, ferreirin, dalbergioidin, and
      naringenin, and one new prenylated isoflavonone, dihydrolicoisoflavone [1].

PMID- 7623043
TI  - Studies on the inhibitory effects of caffeoylquinic acids on monocyte migration
      and superoxide ion production.
AB  - Three caffeoylquinic acids, isolated from the Peruvian plants Tessaria
      integrifolia and Mikania cordifolia that are used medicinally as anti
      inflammatory agents, were tested for their activities on monocyte migration and
      superoxide anion production. 3,5-Di-O-caffeoylquinic and 4,5-di-O-caffeoylquinic
      acids exhibited an appreciable anti-inflammatory activity in vitro, while the
      tricaffeoyl derivative was inactive.

PMID- 7623044
TI  - Amphitoxin, a new high molecular weight antifeedant pyridinium salt from the
      Caribbean sponge Amphimedon compressa.
AB  - A new polymeric pyridinium alkaloid named amphitoxin [2] has been isolated from
      Amphimedon compressa, and its structure determined by spectroscopic analysis. In
      laboratory feeding experiments, crude extracts and purified amphitoxin [2] from
      A. compressa at lower than natural concentration levels effectively deterred
      feeding of a generalist predatory Caribbean reef fish, Thalassoma bifasciatum.

PMID- 7623045
TI  - Chemical and biological investigation of the polar constituents of the starfish
      Luidia clathrata, collected in the Gulf of Mexico.
AB  - Ten new [1-10] and three known [11-13] polyhydroxysteroids were isolated, along
      with four known asterosaponins [14-17], from the starfish Luidia clathrata,
      collected from the offshore waters of the northern Gulf of Mexico. The EtOH
      extracts of this starfish showed feeding-deterrent properties against marine
      fish, and inhibited the settlement of larvae of barnacles and bryozoans, as well
      as the growth of several bacteria. The structures of the new compounds were
      determined by interpretation of their nmr spectral data and by comparison with
      the spectral data of known compounds. The assignment of the configurations of the
      side-chain stereogenic centers of compounds 1 and 3-10 were based on the
      comparison of their nmr data with those of the stereoisomeric model compounds
      after derivatization with the chiral auxiliary MTPA reagent. Larval settlement
      assays conducted on ten isolated compounds revealed they are all potent
      inhibitors of settlement. Two of these isolated compounds inhibited the growth of
      several bacteria.

PMID- 7623046
TI  - New polyoxypregnane ester derivatives from Leptadenia hastata.
AB  - Six new polyoxypregnane esters [1-6] having sarcostin or deacetylmetaplexigenin
      as the aglycones, and acetyl, benzoyl, cinnamoyl, and nicotinoyl residues as the
      ester moieties linked at C-12 and/or at C-20, were isolated from Leptadenia
      hastata. In addition, three new glycosides [7-9] with D-cymarose and D-oleandrose
      linked at C-3 were present in the CHCl3 extract. Structures were deduced on the
      basis of spectral evidence.

PMID- 7623047
TI  - Antineoplastic agents, 326. The stereochemistry of bastadins 8, 10, and 12 from
      the Bismarck archipelago marine sponge Ianthella basta.
AB  - An investigation of cancer cell-growth inhibitory constituents of the Papua New
      Guinea marine sponge Ianthella basta led to isolation of the C-6 hydroxybastadins
      8 [1] 10 [2], and 12 [3]. The absolute stereochemistry (6S) of each bastadin (or
      its tetramethyl ester derivative) was determined by means of the Mosher-Trost
      method. Bastadins 10 [2] and 12 [3] were found to significantly inhibit the
      growth of a selection of human cancer cell lines. Bastadins 8, 10, and 12
      inhibited growth of the Gram-positive opportunists Staphylococcus aureus and
      Enterococcus faecalis.

PMID- 7623048
TI  - Tyrosinase inhibitors from Bolivian medicinal plants.
AB  - Bioassay-guided fractionation monitored by mushroom tyrosinase (EC 1.14.18.1)
      activity, afforded six inhibitors from three Bolivian medicinal plants, Buddleia
      coriacea, Gnaphalium cheiranthifolium, and Scheelea princeps. These inhibitors,
      which are all known phenolic compounds, inhibited the oxidation of L-3,4
      dihydroxyphenylalanine (L-DOPA) mediated by a mushroom tyrosinase.

PMID- 7623049
TI  - Antineoplastic agents, 301. An investigation of the Amaryllidaceae genus
      Hymenocallis.
AB  - Seven species (and one cultivated variety) of Hymenocallis (Amaryllidaceae) and
      the related Pancratium maritima, representing a broad geographical selection,
      were investigated as sources of pancratistatin [1] now undergoing preclinical
      development as an anticancer agent. Pancratistatin [1] was found to be a
      constituent of H. speciosa (Singapore), H. variegated (Singapore), H. pedalis
      (Seychelles), H. expansa (Bermuda), H. sonoranensis (Mexico), and P. maritimum
      (Israel). Only two species of Hymenocallis failed to yield one or more of the
      related cell-growth inhibitory isocarbostyrils such as narciclasine [3a], 7
      deoxynarciclasine [3b], and 7-deoxy-trans-dihydronarciclasine [2].

PMID- 7623050
TI  - Malyngamide H, an ichthyotoxic amide possessing a new carbon skeleton from the
      Caribbean cyanobacterium Lyngbya majuscula.
AB  - Guided by ichthyotoxic activity against goldfish, a new lipopeptide, malyngamide
      H [1], and its corresponding free acid, 7-methoxytetradec-4(E)-enoic acid [2],
      have been isolated from the tropical marine cyanobacterium Lyngbya majuscula. The
      structure of the new carbon skeleton borne by malyngamide H was elucidated on the
      basis of spectroscopic analysis, mainly 2D nmr. The absolute stereochemistry of
      the cyclohexenone moiety of malyngamide H [1] was deduced by a combination of 2D
      NOESY and exciton chirality circular dichroism spectroscopy.

PMID- 7623051
TI  - A novel phorbol ester from Excoecaria agallocha.
AB  - The novel phorbol ester 12-deoxyphorbol 13-(3E,5E-decadienoate) [1] was isolated
      as the anti-HIV principle of Excoecaria agallocha leaves and stems collected in
      northwest Australia. The structure was determined by spectral means. Compound 1
      was also a potent displacer of [3H]-phorbol dibutyrate from rat brain membranes.

PMID- 7623052
TI  - A new polyether acid from a cold water marine sponge, a Phakellia species.
AB  - A new polyether acid, 14, 15-dihydrodinophysistoxin-1 [1], was isolated along
      with dinophysistoxin-1 [2] and okadaic acid [3], from an unidentified species of
      the sponge genus Phakellia. The structure of 1 was assigned by comparison of its
      1H- and 13C-nmr and fabms spectral data to those of 2 and 3, as well as
      interpretation of homonuclear 2D nmr data. Compounds 1-3 showed cytotoxicity
      against L-1210 leukemia cells with IC50 values of 3 ng/ml. The isolation,
      structure determination, and biological activities of these compounds are
      described (1).

PMID- 7623053
TI  - Erroneous mass spectrometer readings caused by desflurane and sevoflurane.
AB  - OBJECTIVE: Medical mass spectrometers are configured to detect and measure
      specific respiratory and anesthetic gases. Unrecognized gases entering these
      systems may cause erroneous readings. We determined how the Advantage 1100
      (Perkin-Elmer, now Marquette Gas Systems, Milwaukee, WI) and PPG-SARA (PPG
      Biomedical Systems, Lenexa, KS) systems that were not configured to measure
      desflurane or sevoflurane respond to increasing concentrations of these new
      potent volatile anesthetic agents. METHODS: Desflurane 0% to 18% in 3% increments
      or sevoflurane 0% to 7% in 1% increments in 5-L/min oxygen was delivered to the
      Advantage and PPG-SARA mass spectrometry systems. For each concentration of each
      agent, the displayed gas analysis readings and uncompensated collector plate
      voltages were recorded. RESULTS: The Advantage 1100 system read both desflurane
      and sevoflurane mainly as enflurane and, to a lesser extent, as carbon dioxide
      and isoflurane. For enflurane(E) readings < 9.9%, the approximate relationships
      are: %Desflurane = 1.6E; %Sevoflurane = 0.3E. These formulas do not apply if E >
      9.9% because of saturation of the summation bus. PPG-SARA read desflurane mainly
      as isoflurane(I) and, to a lesser extent, as nitrous oxide. PPG-SARA read
      sevoflurane mainly as enflurane(E) and, to a lesser extent, as nitrous oxide and
      halothane. The approximate relationships are: %Desflurane = 1.11 (for I < 9%);
      %Sevoflurane = 2.1E. CONCLUSIONS: Advantage 1100 and PPG-SARA systems not
      configured for desflurane or sevoflurane display erroneous anesthetic agent
      readings when these new agents are sampled. Advantage 1100 also displays falsely
      elevated carbon dioxide readings when desflurane is sampled.

PMID- 7623054
TI  - Measurement of respiratory rate and timing using a nasal thermocouple.
AB  - OBJECTIVE: The aims of this study were to assess aspects of the response of a
      small thermocouple to temperature change, and to evaluate whether such a
      thermocouple could be used intermittently to measure respiratory rate and timing
      by detecting the changes in nasal temperature occurring with breathing. METHODS:
      The study had three parts. First, three similar, fast-responding thermocouples
      were immersed repeatedly in warm water. Second, the influence of atmospheric
      temperature on the signal of a thermocouple placed at different sites within the
      nasal orifice was studied. The signals produced were continuously displayed and
      analyzed using a laptop computer to allow evaluation of the thermocouples'
      response characteristics. Third, simultaneous respiratory recordings were
      acquired using a nasal thermocouple and a nasal pneumotachograph in 12 teenaged
      subjects. The respiratory rate and the periods of time taken for inspiration (Ti)
      and expiration (Te) were calculated and compared. RESULTS: The thermocouples'
      responses to the temperature changes associated with breathing and immersion into
      water were rapid and consistent. The rate of the signals' decay, following the
      peak signal marking expiration, was influenced by the atmospheric temperature.
      The time constants of the thermocouples were similar (mean time constant = 0.41
      sec, standard deviation (SD) = 0.07). Optimal respiratory recordings were
      obtained, with least discomfort, when the thermocouple was positioned at 0 to 4
      mm within the nasal orifice. In comparing the respiratory recordings acquired
      simultaneously with a thermocouple and pneumotachograph, the respiratory rates
      were identical, and the Ti and Te values were similar (mean difference 0.04 sec
      (95% CI: -0.11 to 0.21 sec) and -0.04 sec (95% CI: -0.20 to 0.12 sec),
      respectively). CONCLUSIONS: Intermittent measurements of respiratory rate and
      timing using a nasal thermocouple accurately reflected measurements obtained from
      nasal airflow using a pneumotachograph.

PMID- 7623055
TI  - A linear approximation of Brody's equation to predict oxygen consumption in adult
      humans.
AB  - OBJECTIVE: The objective of our study was to derive a linear approximation to
      Brody's equation for oxygen consumption as a simpler alternative for the
      clinician. METHODS: The approximation was derived by using calculus to construct
      a line tangent to Brody's equation at 81 kg. RESULTS: The linear approximation
      was derived to be: VO2 = (2.5w + 67.5) ml/min, where w is the subject's weight in
      kilograms. The error introduced by this linear approximation is 10.9% at 30 kg
      and 1.35% at 120 kg. CONCLUSIONS: This linear equation may have utility for
      approximating oxygen consumption when an approximation is required, as in closed
      circuit anesthesia. The utility of this equation is that it is linear and
      produces a result similar to Brody's equation.

PMID- 7623056
TI  - Refractive indices for volatile anesthetic gases: equipment and method for
      calibrating vaporizers and monitors.
AB  - OBJECTIVE: The objective of our study was to establish the refractive indices and
      the virial coefficients of the volatile anesthetic vapors. These indices and
      coefficients will allow refractometry to be used by manufacturers to produce
      accurate calibration, without requiring expensive high-precision calibration
      gases. METHODS: We used a precision refractometer to measure the refractive
      indices for five volatile anesthetic vapors. We prepared our calibration gases by
      mixing a gravimetrically calibrated amount of liquid agent with a constant gas
      flow. RESULTS: The refractive indices for the volatile anesthetic vapors are
      1,603.2 for halothane, 1,540.4 for enflurane, 1,563.3 for isoflurane, 1,538.3 for
      sevoflurane, and 1,211.7 for desflurane. The maximum theoretical error in our
      measurements, due to all sensors and all uncertainty in our measurement of
      apparatus and physical constants, is +/- 0.56% of the reading (+/- 0.70% for
      desflurane). CONCLUSIONS: If refractometry replaced calibration gases in
      cylinders, as a calibration standard, manufacturers might avoid errors that now
      occur because calibration gases manufactured by numerous companies seem to
      differ. We propose that our values serve as an interim database.

PMID- 7623057
TI  - Terminology and the current limitations of time capnography: a brief review.
AB  - The carbon dioxide (CO2) trace versus time (time capnography) is convenient and
      adequate for clinical use. This is the method most commonly utilized in
      capnography. However, the current terminology in time capnography has not yet
      been standardized and is, therefore, a potential source of confusion. Standard
      terminology that is based on convention and logic to represent the various phases
      of a time capnogram is essential. The time capnogram should be considered as two
      segments: an inspiratory segment and an expiratory segment. The inspiratory
      segment is termed as phase ); the expiratory segment is divided into phases I,
      II, III, and, occasionally, IV. Phase I represents the CO2-free gas from the
      airways (anatomical dead space); phase II consists of a rapid S-shaped upswing on
      the tracing due to mixing of dead space gas with alveolar gas; and phase III, the
      alveolar plateau, represents CO2-rich gas from the alveoli. The physiologic basis
      of phase IV, the terminal upswing at the end of phase III, which is observed in
      capnograms recorded under certain circumstances (such as in pregnant subjects and
      obese subjects) is discussed in detail. The clinical implications of the alpha
      angle, which is the angle between phases II and III, and the beta angle, which is
      the angle between phases III and the descending limb of phase 0, are outlined.
      The subtle but important limitations of time capnography are reviewed; its
      current status as well as its future potential are explored.

PMID- 7623058
TI  - Safety and efficacy of a ventilator database interface.
AB  - This report describes a ventilator dysfunction that arose during the mechanical
      ventilation of a lung transplant recipient. The problem was discovered because
      the data on the computer-based information management system (CIMS) was different
      from that on the ventilator's dials. This incident is important because of the
      continued extensive use of analog mechanical ventilators, the increasing
      popularity of CIMS, and the patient safety implications of the incident.

PMID- 7623059
TI  - Spurious ST segment depression by automated ST segment analysis.
AB  - Perioperative myocardial ischemia has been shown to be predictive of adverse
      cardiac outcome [1]. One method of detecting intraoperative myocardial ischemia
      is automated ST segment monitoring [2]. The rationale behind automated ST
      monitoring is that the clinician will be promptly alerted to ischemic changes in
      the ECG. This may lead to earlier intervention and, perhaps, improved outcome
      [3]. We describe a case in which automated ST segment monitoring falsely signaled
      the presence of intraoperative ST segment depression. This event emphasizes the
      importance of confirming the validity of ST segment changes before instituting
      therapy.

PMID- 7623060
TI  - Classification-algorithm evaluation: five performance measures based on confusion
      matrices.
AB  - OBJECTIVE: The objective of this paper is to introduce, explain, and extend
      methods for comparing the performance of classification algorithms using error
      tallies obtained on properly sized, populated, and labeled data sets. METHODS:
      Two distinct contexts of classification are defined, involving "objects-by
      inspection" and "objects-by-segmentation." In the former context, the total
      number of objects to be classified is unambiguously and self-evidently defined.
      In the latter, there is troublesome ambiguity. All five of the measures of
      performance here considered are based on confusion matrices, tables of counts
      revealing the extent of an algorithm's "confusion" regarding the true
      classifications. A proper measure of classification-algorithm performance must
      meet four requirements. A proper measure should obey six additional constraints.
      RESULTS: Four traditional measures of performance are critiqued in terms of the
      requirements and constraints. Each measure meets the requirements, but fails to
      obey at least one of the constraints. A nontraditional measure of algorithm
      performance, the normalized mutual information (NMI), is therefore introduced.
      Based on the NMI, methods for comparing algorithm performance using confusion
      matrices are devised. CONCLUSIONS: The five performance measures lead to similar
      inferences when comparing a trio of QRS-detection algorithms using a large data
      set. The modified NMI is preferred, however, because it obeys each of the
      constraints and is the most conservative measure of performance.

PMID- 7623061
TI  - An expert system to teach troubleshooting of common problems associated with the
      automated anesthesia recordkeeper.
AB  - Automated anesthesia recordkeepers have been used to monitor patients during
      surgery in up to 90% of cases at The Ohio State University. The record-keeping
      devices are complex and can be difficult to troubleshoot. The 1st-CLASS Fusion
      Program, an expert system "shell-program," has been programmed to allow the
      resident or nurse anesthetist to solve the two most common types of problems
      associated with the recordkeeper: printer problems and patient monitor problems.
      Use of this program allows the resident or nurse anesthetist to troubleshoot the
      recordkeeper quickly and accurately and promotes in the user a sense of
      competence and control over the technology.

PMID- 7623062
TI  - Write it right.

PMID- 7623063
TI  - Write it right, Part IV: Testing, distributing, and checklist summary.

PMID- 7623064
TI  - In my opinion: carbon monoxide: what should we do?

PMID- 7623065
TI  - Measurement of CO2 response with the breath-by-breath automatic acquisition of
      the breathing pattern and occlusion pressure.

PMID- 7623066
TI  - Determinants of drug response in camptothecin-11-resistant glioma cell lines.
AB  - Camptothecin-11 (CPT-11) is a new derivative of camptothecin, a plant alkaloid
      antitumor agent. Previous studies indicated that antitumor activity of CPT-11 was
      mediated through interaction of the drug with its target enzyme, DNA
      topoisomerase I (topo I). To elucidate the mechanisms of CPT-11 resistance, we
      have characterized glioma cell lines (T98G/CPT-11, C6/CPT-11) selected from the
      wild types (T98G. C6) for acquired resistance to CPT-11. T98G/CPT-11 and C6/CPT
      11 cells demonstrated 5.4- and 7.3-fold increases, respectively, in resistance to
      CPT-11. Total glutathione S-transferase (GST) and GST-p activities were similar
      in CPT-11-sensitive and -resistant cells. No difference in intracellular
      accumulation of CPT-11 was observed between CPT-11-resistant and parental cells,
      indicating that an alteration in the uptake was not responsible for resistance.
      In addition, CPT-11-resistant cell lines showed no change in the total activity
      of Topo I, indicating an alteration in total Topo I was not responsible for
      resistance. In contrast, significantly increased intracellular glutathione (GSH)
      levels levels were found in T98G/CPT-11 and C6/CPT-11 cells (4.3- and 2.1-fold).
      Furthermore, Topo I samples from T98G/CPT-11 and C6/CPT-11 cells were at least 4-
      and 2-fold more resistant to the inhibitory effect of the CPT-11 on the
      relaxation activity of Topo I than were Topo I samples from their respective
      parent lines. The resistance of the enzyme itself to the effects of CPT-11 may be
      responsible for the resistance to CPT-11. Thus, at least two distinct mechanisms
      have been selected for the CPT-11-resistant cells.

PMID- 7623067
TI  - An experimental model of leptomeningeal metastases employing rat mammary
      carcinoma cells.
AB  - Five percent of patients dying with breast cancer have leptomeningeal metastases
      (LM) but current therapy is of only marginal benefit. Therefore, an experimental
      model of LM from breast cancer was developed to facilitate the development of
      novel therapies. Cell suspensions of 13762 MAT BIII rat mammary carcinoma cells
      are injected into the cisterna magna of adult, female Fischer 344 rats under
      general anesthesia. 10-12 days after the injection of 2 x 10(5) viable cells,
      animals develop neurologic signs, including ataxia, paralysis and spontaneous
      rotation. Histologically, tumor cells can be seen in the subarachnoid space over
      the surface of the brain and spinal cord and within the ventricles. Tumor cells
      do not invade the brain parenchyma. Collections of tumor cells are extensively
      infiltrated by macrophages and CD8-positive (suppressor/cytotoxic) T cells, but
      by few CD4-positive (helper) T cells. MAT BIII cells therefore provide a model of
      LM from breast cancer with a reproducible clinical course and histologic
      features. The tumor elicits a cellular immune response and can be useful in
      exploring biologic therapies for leptomeningeal metastases.

PMID- 7623068
TI  - Increased intracellular cyclic AMP levels suppress the mitogenic responses of
      human astrocytoma cells to growth factors.
AB  - It has been shown that the intracellular cAMP levels were decreased in human
      malignant astrocytomas. On the other hand, various growth factors and their
      receptors were found to be overexpressed in these tumors. It is therefore
      intriguing as to whether there is interplay between the two phenomena in the
      modulation of the astrocytoma cell growth. In a basal medium consisting of 75%
      DMEM, 25% Ham's F-12 supplemented with 2% FBS, we show that the mitogenic effects
      of platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF),
      and epidermal growth factor (EGF) on human astrocytoma cells were suppressed by
      dibutyryl-cAMP. Dibutyryl-cAMP alone neither potentiated nor inhibited the tumor
      cell growth. Further studies show that PDGF-induced receptor autophosphorylation
      in human astrocytoma cells is suppressed by increased intracellular cAMP levels
      as measured by immunoprecipitation with anti-PDGF receptor and
      antiphosphotyrosine antibodies. Our results indicate that there is antagonistic
      interplay between the receptor tyrosine kinase pathway and cAMP-dependent protein
      kinase pathway in the control of the malignantly transformed glial cells. A
      reduced cAMP level seen in many human astrocytoma cells may favor their response
      to growth factor mitogenesis.

PMID- 7623070
TI  - Turcot's syndrome: case report and review of the classification.
AB  - We report a case of association of a brain tumor with multiple colorectal
      polyposis and offer an analysis of the relevant literature with a view to
      revising the classification of the syndrome in relation to familial multiple
      polyposis and Gardner's syndrome. Differences emerged, depending on the brain
      tumor type, which suggests that this association may be classified as two
      distinct syndromes.

PMID- 7623069
TI  - Clinical application of 18F-FUdR in glioma patients--PET study of nucleic acid
      metabolism.
AB  - Positron emission tomography was used to investigate the metabolism of nucleic
      acids by 18F-fluoro-2'-deoxyuridine (18F-FUdR) in 22 patients with gliomas.
      Sixteen cases of high grade glioma clearly demonstrated a region of high activity
      with a differential absorption rate (DAR) of 0.64 +/- 0.34. Six cases of low
      grade glioma failed to reveal a positive image of the tumor and the DAR in tumor
      was 0.21 +/- 0.042 (p < 0.01). This PET-18F-FUdR study succeeded in
      differentiating high and low grade gliomas from the view point of nucleic acid
      metabolism.

PMID- 7623071
TI  - Positron emission tomographic assessment of cerebral hemocirculation and glucose
      metabolism in malignant glioma following treatment with intracarotid recombinant
      human tumor necrosis factor-alpha.
AB  - Cerebral hemocirculation and glucose metabolism in a malignant astrocytoma were
      repeatedly quantified before and after intracarotid injection of recombinant
      human tumor necrosis factor-alpha (rH-TNF) using positron emission tomography
      (PET). The patient received an intracarotid injection of a 3 x 10(4) U/m2 dose of
      rH-TNF three times over a two week period. PET was performed prior to and 24 hr
      after the first injection, and two weeks after the third injection. Prior to the
      first rH-TNF treatment, two lesions demonstrating high perfusion and
      hypermetabolism of glucose were noted in the right frontal and temporal regions.
      The frontal hypermetabolic lesion showed decreases in hemocirculation and
      metabolism 24 hr after the first injection and then increases beyond the pre
      treatment level two weeks after the third treatment, whereas the temporal lesion
      remained unchanged during the follow-up period. No appreciable changes were noted
      in the adjacent cortex where rH-TNF was perfused, with the exception of a
      transient decrease in regional blood volume. Magnetic resonance images of the
      tumor showed no changes as a result of treatment with intracarotid rH-TNF.
      Intracarotid rH-TNF preferentially affects tumor tissue as opposed to normal
      cortex.

PMID- 7623072
TI  - Single brain metastases from unknown primary malignancies in CT-era.
AB  - Cerebral metastases account for about half of all intracranial neoplasms. In 33%
      66% they represent the first sign of a systemic tumor. We report our experience
      in 100 patients with solitary brain metastasis from unknown primary malignancies
      treated between 1976 and 1988. All patients were treated surgically and 81 also
      received radiotherapy and chemotherapy. Postoperative mortality was 6%. Mean
      survival in those patients with unknown primary tumor at intracranial surgery was
      15.3 months as compared to 31.6 months in those in whom it remained unidentified
      during life. The usual cause of death was growth of the systemic cancer.

PMID- 7623073
TI  - Intraoperative radiotherapy for gliomas.
AB  - Intraoperative radiotherapy (IORT) was performed in 20 of 36 patients with
      glioma; 11 glioblastomas, 7 malignant astrocytomas, 2 benign astrocytomas. Twenty
      or 25 Gy of irradiation was delivered in a single fraction intraoperatively,
      followed by external beam irradiation. The electron beam energy was selected so
      that the 80% isodose line fell at 2 or 3 cm below the residual tumor surface.
      Median survival time of IORT group was 14 months and that of the control group
      was 10 months. Difference of survival curve was significant. There were 6
      incidences of complication caused by IORT; 1 radionecrosis, 1 convulsion, 1
      abscess, and 3 severe brain edemas. IORT is suited for the treatment of malignant
      gliomas.

PMID- 7623075
TI  - Growth-inhibiting effect of intratumoral recombinant human tumor necrosis factor
      on an experimental model of primitive neuroectodermal tumor.
AB  - The effect of intratumoral administration of recombinant human tumor necrosis
      factor on an experimental model of primitive neuroectodermal neoplasia was
      studied. A clear inhibition of tumor growth was achieved by immunotherapy that
      consisted in intralesion injections of 100 micrograms of tumor necrosis factor
      daily, the first three days of each week, for a period of four weeks. At this
      time, tumor size was 2.21 +/- 0.66 cm2 (mean +/- standard deviation) in the
      treated group, versus 7.62 +/- 0.43 cm2 in the control group. These data support
      previous studies on the influence of tumor necrosis factor on the development of
      ethyl-nitrosourea-induced tumors, and suggest the potential usefulness of this
      cytokine in human primitive neuroectodermal neoplasms.

PMID- 7623076
TI  - Inertial representation of angular motion in the vestibular system of rhesus
      monkeys. II. Otolith-controlled transformation that depends on an intact
      cerebellar nodulus.
AB  - 1. We recently studied the spatial representation of angular motion signals in
      rhesus monkeys by examining the orientation of postrotatory vestibuloocular
      responses during tilt of the head and body relative to gravity after constant
      velocity rotation about an earth-vertical axis. We have reported that low
      frequency angular motion signals in the vestibuloocular reflex (VOR) of rhesus
      monkeys are spatially transformed such that they remain invariant relative to
      gravity. In the present study we examine the properties of these inertial
      vestibular signals by employing similar stimulation conditions in animals with
      either selective semicircular canal plugging or selective lesions of cerebellar
      lobule X (nodulus) and ventral lobule IX (uvula). 2. We studied the spatial
      organization of postrotatory VOR in two rhesus monkeys that had either the
      lateral or one of the vertical canal pairs inactivated by plugging. In both
      monkeys, the spatiotemporal characteristics of postrotatory velocity after
      rotation in the plane of an intact canal pair and tilting in the plane of the
      plugged canal pair were indistinguishable from those of intact animals:
      postrotatory responses after tilts in the plane of the plugged canal pair were
      strongly damped, whereas an orthogonal response component was generated that
      rotated the eye velocity vector toward alignment with gravity. Thus otolith
      information rather than transient semicircular canal inputs that normally coexist
      during tilts seem to provide the necessary cues for the central transformation of
      semicircular canal signals. 3. We studied the three-dimensional VOR properties in
      two animals in which the cerebellar nodulus and ventral uvula were surgically
      ablated. After these lesions the temporal properties of the horizontal, vertical,
      and torsional VOR during earth-vertical-axis rotations were differentially
      affected. For horizontal VOR, the duration of postrotatory nystagmus was
      prolonged and the responses acquired strongly underdamped (i.e., oscillatory)
      properties. Similarly, sinusoidal responses were characterized by smaller phase
      leads after the lesion. For torsional VOR, the duration of postrotatory nystagmus
      was significantly shorter after the lesions, reaching postlesion values of 3.6 +/
      1.7 (SD) s and 6.4 +/- 1.1 s compared with prelesion values of 22.4 +/- 4.5 and
      33.6 +/- 5.3 s for each animal. In addition, large phase leads characterized the
      torsional VOR during low-frequency sinusoidal stimulation. The dynamic properties
      of the vertical VOR in the lesioned animals, on the other hand, were
      indistinguishable from those in controls. 4. The cerebellar lesions affected the
      spatial organization of the horizontal and vertical/torsional systems in a
      differential way. Inertial transformation of lateral canal activity was only
      partially affected.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7623074
TI  - Phase II study of amonafide in patients with recurrent glioma.
AB  - Amonafide, a novel imide derivative with broad preclinical antitumor activity,
      achieves significant cerebrospinal fluid levels in animal models. In order to
      test its antitumor activity in patients with recurrent diffuse infiltrative
      glioma of the astrocytic and oligodendroglial type, we performed a phase II
      clinical trial. Of the 22 eligible and evaluable patients treated, 2 (9%)
      experienced tumor regression lasting more than one year. No other patients
      experienced tumor regression; one remained stable more than six months.
      Toxicities consisted primarily of myelosuppression, vomiting, and venous
      irritation at the infusion site. We conclude that amonafide has minimal activity
      in recurrent glioma patients. Further investigations are not warranted in this
      study population.

PMID- 7623077
TI  - Unmyelinated nociceptors of rat paraspinal tissues.
AB  - 1. We made recordings from rat dorsal root filaments to study unmyelinated
      afferent units (conduction velocity < or = 1.5 m/s) associated with deep
      paraspinal tissues of the dorsal sacrum and proximal tail. Data from 57
      unmyelinated units were analyzed in 47 experiments. Receptive fields were
      identified in intact animals and then surgically isolated using microdissection.
      Units were characterized using mechanical, noxious chemical, and thermal stimuli.
      2. These recordings revealed innervation of the nerve sheaths and surrounding
      connective tissue, muscles, tendons, and tissue apposed to the undersurface of
      the skin. No units were found with receptive fields directly on joint capsular
      tissue. The receptive fields of the units were often multiple and located in more
      than one tissue; 31 of 57 units showed convergence from different tissues. 3. The
      units with receptive fields on neurovascular bundles shared sensitivities with
      other deep tissue units described in this and other reports. These units may have
      clinical importance in pain due to peripheral neuropathies. 4. The units
      initially responded to strong mechanical stimulation of the intact animal and
      often to noxious stretch of the tail. Once surgically isolated, an individual
      unit's threshold to mechanical stimuli appeared lower. 5. Capsaicin (0.001%-0.1%)
      elicited responses in 81% (17 of 21) of the units tested. Bradykinin (20
      micrograms/ml) elicited responses in 45% (10 of 22) of the units tested. Noxious
      cold (4-10 degrees C) and hot (55 degrees C) stimulation elicited discharges from
      33% (5 of 15) and 25% (5 of 20) of the units tested, respectively. 6. The
      unmyelinated units had similar mechanical, chemical, and thermal sensitivities.
      These similarities and the observed convergence only allowed separation of units
      by the tissue in which the ending was found, and did not allow further
      classification. 7. The prevalence of background discharge suggested that many
      units were sensitized during the experiments. 8. The sensitivities of these
      paraspinal units were similar to those reported for other tissues. Because of the
      anatomic similarity of the paraspinal tissues of the proximal tail and the lumbar
      spine, the conclusions of the present study can be related to the lumbar spine.
      These afferent units are thought to participate in nociception from the deep
      paraspinal tissues.

PMID- 7623078
TI  - Ca(2+)-dependent plasticity of miniature inhibitory postsynaptic currents after
      amputation of dendrites in central neurons.
AB  - 1. The effects of cutting off the bulk (> 2/3) of the dendritic tree (dendrotomy)
      on GABAergic miniature inhibitory postsynaptic currents (mIPCSs) were studied in
      granule cells of the adult rat dentate gyrus in 400-microns-thick slices in
      vitro. 2. After dendrotomy carried out in warm (32 degrees C) control artificial
      cerebrospinal fluid (ACSF), only small antidromic population spikes could be
      evoked in the granule cell layer, and no viable whole cell recordings could be
      obtained. However, when dendrotomy was performed in cold (8-10 degrees C) control
      ACSF, the amplitude of the antidromic population spikes increased, and stable
      whole cell recordings became possible. 3. Whole cell recordings, with CsCl-filled
      pipettes, from granule cells dendrotomized in cold control ACSF, revealed
      significant alterations, lasting > 10 h, in the decay kinetics of mIPSACs. The
      change consisted of a calcium-dependent transformation of the normal, single
      exponential decay into a prolonged double exponential that effectively increased
      the charge transferred by the synaptic events (the total area of the currents) by
      67%. When 30 mM 1,2 bis-(2-aminophenoxy)-N,N,N',N'-tetraacetic acid (BAPTA) was
      included in the pipette, the changes in the mIPSCs decay kinetics could still be
      observed after dendrotomy, indicating that the maintenance phase of this
      plasticity did not depend on elevated intracellular calcium levels. 4. Viable
      whole cell recordings could also be obtained in dendrotomized granule cells when
      the amputation of dendrites was carried out at 32 degrees C after incubation for
      2 h with the cell-permeant Ca2+ chelator, BAPTA-AM (50 microM), or the cutting
      process was done in an ACSF containing either a combination of excitatory amino
      acid receptor antagonists 2-amino-5-phosphonovaleric acid (APV; 25 microM) + 6
      cyano-7-nitroquinoxaline-2,3-dione (CNQX; 10 microM), a blocker of intracellular
      Ca2+ release dantrolene-Na (20 microM), or the voltage-gated Na+ channel blocker
      tetrodotoxin (TTX; 1 microM). 5. After dendrotomy in BAPTA-AM, APV + CNQX, APV +
      CNQX + TTX, and/or dantrolene, the changes in decay kinetics were prevented,
      indicating that a rise in intracellular Ca2+ concentration plays a pivotal role
      in this plasticity. 6. Computer simulations of mIPSCs suggested that changes in
      single channel kinetics alone can, in principle, account for the Ca(2+)-dependent
      changes in mIPSC decay kinetics. 7. These findings are consistent with a lasting
      Ca(2+)-dependent increase in gamma-aminobutyric acid-A (GABAA) receptor function
      in cells that survive physical injury to their dendrites.

PMID- 7623079
TI  - Graded responses and spiking properties of identified first-order visual
      interneurons of the fly compound eye.
AB  - 1. We studied the graded and spiking properties of the "non-spiking" first-order
      visual interneurons of the fly compound eye in situ with the use of intracellular
      recordings. Iontophoretical QX-314 injections, Lucifer yellow marking, and
      (discontinuous) current-clamp method together with transfer function analysis
      were used to characterize the neural signal processing mechanisms in these
      neurons. 2. A light-OFF spike was seen in one identified anatomic subtype (L3, n
      = 6) of the three first-order visual interneurons (L1, L2, and L3, or LMCs) when
      recorded from synaptic region (i.e., in the 1st visual ganglion, lamina
      ganglionaris) in dark-adapted conditions. Hyperpolarization of the membrane
      potential by current caused the identified L1 (n = 4), as well as L3 (n = 6), to
      produce an OFF spike, a number of action potentials, and some subthreshold
      depolarizations after the light-ON response. In L2 the OFF spike or action
      potentials could not be elicited. 3. To produce action potentials in L1 and L3,
      it was found to be necessary to hyperpolarize the cells approximately 35-45 mV (n
      = 43) below the resting potential (RP) in the synaptic zone. Recordings from the
      axons of these cells revealed that near the second neuropil (chiasma) the
      threshold of these spikes was near to (approximately 10 mV below, n = 16) or even
      at the RP when an ON spike was also produced (n = 4). 4. The recorded spikes were
      up to 54 mV in amplitude, appeared with a maximum frequency of up to 120
      impulses/s, and had a duration of approximately 8 ms. In L1 and L3 the spikes
      were elicited either after a light pulse (L3) or after a negative current step
      that was superimposed on a hyperpolarizing steady-state current (L3 and L1). A
      positive current step (similarly superimposed on a hyperpolarizing steady-state
      current) also triggered the spikes during the step. 5. Iontophoretic injection of
      a potent intracellularly effective blocker of voltage-gated sodium channels, QX
      314, irreversibly eradicated the spikes and subthreshold depolarizations (n = 5).
      In addition, further injections elongated the light-ON responses and decreased or
      even abolished the light-OFF response. 6. Negative prepulses followed by positive
      current steps were applied from the RP, to test the activation-inactivation
      properties of the channels responsible for the OFF spike.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 7623080
TI  - Interaction of opioids and membrane potential to modulate Ca2+ channels in rat
      dorsal root ganglion neurons.
AB  - 1. Using patch-clamp methods, we show that brief prepulses to very positive
      voltages increase (facilitate) the amplitude of current through Ca2+ channels
      during a subsequent test pulse in some, but not all, dorsal root ganglion (DRG)
      sensory neurons. The amplitude of this facilitated current generally increases
      when the Ca2+ channels are inhibited by activation of the mu-opioid receptor. 2.
      The facilitated current is blocked by omega-conotoxin GVIA, activates in the
      range of high-threshold Ca2+ channels, and inactivates at relatively negative
      holding voltages. Thus facilitated current passes through N-type Ca2+ channels,
      the same channels that are inhibited by opioids and control neurotransmitter
      release in sensory neurons. 3. Although maximal facilitation occurs only at
      unphysiologically high membrane potentials (above +100 mV), some facilitation is
      seen after prepulses to voltages reached during action potentials. After return
      to the holding potential, facilitation persists for hundreds of milliseconds,
      considerably longer than in other neurons. Brief trains of pulses designed to
      mimic action potentials caused small facilitation (19% of maximal) in a fraction
      (8 of 24) of opioid-inhibited neurons. 4. We conclude that 1) prepulses to
      extremely positive voltages can cause partial recovery of Ca2+ channels inhibited
      by opioids; and 2) small, but detectable, facilitation is also seen after
      physiological stimulation in some DRG neurons. Facilitation, largely considered a
      biophysical epiphenomenon because of the extreme voltages used to induce it,
      appears to be physiologically relevant during opioid inhibition of Ca2+ channels
      in DRG neurons.

PMID- 7623081
TI  - Spike frequency adaptation studied in hypoglossal motoneurons of the rat.
AB  - 1. We studied spike frequency adaptation of motoneuron discharge in the rat
      hypoglossal nucleus using a brain stem slice preparation. The characteristics of
      adaptation in response to long (60 s) injected current steps were qualitatively
      similar to those observed previously in cat hindlimb motoneurons. The discharge
      rate typically exhibited a rapid initial decline, characterized by a linear
      frequency-time relation, followed by a gradual exponential decline that continued
      for the duration of current injection. However, a more systematic, quantitative
      analysis of the data revealed that there were often three distinct phases of the
      adaptation rather than two. 2. The three phases of adaptation (initial, early,
      and late) were present in at least one 60-s trial of repetitive firing in all but
      a small number of motoneurons. Initial adaptation was limited to the first few
      spikes except in a few trials (7%) in which there was no initial adaptation. The
      time course of the subsequent decline in rate could be adequately described by a
      single-exponential function in about half of the trials (48%). In the remaining
      trials this subsequent decline in frequency was better described as the sum of
      two exponential functions: an early phase, lasting < 2 s, and a late phase, which
      lasted for the duration of the discharge period. 3. The magnitude of initial
      adaptation was correlated with the initial firing frequency (i.e., the reciprocal
      of the 1st interspike interval). The magnitudes of the early and late phases of
      adaptation were correlated with the firing frequency reached at the end of
      initial adaptation. Neither the magnitudes nor the time courses of the three
      phases were correlated with other membrane properties such as input resistance,
      rheobase, or repetitive firing threshold. 4. The slope of the frequency-current
      (f-I) curve was steeper in the initial phase (first 2-5 spikes) than in either
      the early (< 2 s) or late (> 2 s) phases of adaptation as previously reported by
      other investigators. In the absence of early adaptation, a steady state for the f
      I slope was reached by 0.7-1 s, the time typically reported in studies of
      repetitive discharge. However, when early adaptation was present (50% of the
      trials), a steady-state value for the f-I slope was not reached until the cell
      had discharged for > 1 s. 5. To characterize the time course of firing rate
      recovery from the adaptive processes, the current was turned off for periods of <
      or = 10 s during the course of a 60-s trial.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7623082
TI  - Functional changes in dorsal root ganglion cells after chronic nerve constriction
      in the rat.
AB  - 1. We studied the effects of a chronic nerve constriction on the evoked responses
      in dorsal root fibers in the rat to norepinephrine and to thermal stimuli applied
      either to the dorsal root ganglion (DRG) or the site of nerve injury. We recorded
      a total of 59 C fibers, 15 A delta-fibers, and 46 A beta-fibers from the L5
      dorsal root of the rats 11-52 days after a loose ligation of the ipsilateral
      sciatic nerve. Most fibers were identified by the presence of spontaneous
      activity (SA) that originated partially at and/or proximal to the injury site. In
      addition, we recorded 20 C fibers, 1 A delta-fiber, and 28 A beta-fibers from the
      dorsal roots of normal, uninjured neurons. 2. In nerve-injured rats, the SA of
      some C fibers was generally increased by cooling and decreased by heating either
      site. In contrast, the SA of most A beta-fibers was increased by heating either
      the injury site or the DRG. Cooling the DRG decreased SA in A beta-fibers,
      whereas cooling the injury site typically had no effect. Excitatory responses
      were not evoked in any fiber group when the same thermal stimuli were applied to
      the nerve or DRG tested in normal, uninjured rats. 3. Norepinephrine (< 0.5 mM)
      applied either to the injury site or the DRG increased the SA of most C fibers
      and A delta-fibers but only a minority of A beta-fibers in previously injured
      nerves. The threshold concentration for excitation of the DRG somata of C fibers
      was 0.01 mM. No effects were found for fibers in uninjured nerves. 4. The effect
      of norepinephrine was blocked by a pretreatment with yohimbine, an alpha 2
      blocker, but not with prazosin, an alpha 1-blocker. 5. Stimulation of the
      sympathetic trunk (L2-L3) excited most C fibers and a minority of A beta-fibers.
      In contrast, the SA of a minority of C fibers and A beta-fibers was depressed
      during sympathetic stimulation. 6. After a chronic nerve constriction the DRG
      becomes a source of abnormal activity modulated by sympathetically released
      norepinephrine acting on alpha 2 receptors in DRG somata. This neuropathic
      activity may contribute to cutaneous pain and hyperalgesia.

PMID- 7623083
TI  - Developmental increase in CA3-CA1 presynaptic function in the hippocampal slice.
AB  - 1. We recorded extracellular and intracellular CA3-CA1 synaptic responses in
      hippocampal slices from neonatal rats [postnatal day (P) 15-21 and P29-35].
      Presynaptic function was examined by measuring input-output relationships and
      paired-pulse facilitation and by quantal analysis of minimally evoked responses.
      2. Extracellular recording revealed no difference in excitatory postsynaptic
      potential (EPSP) threshold or the fiber potential response for a given stimulus
      intensity between the two age groups. However, the slope of the field EPSP was
      consistently larger in older animals. The increase in EPSP slope was associated
      with a decrease in paired-pulse facilitation, suggesting an increase in
      presynaptic function with postnatal development. 3. Extracellular results were
      confirmed by intracellular recordings that revealed no difference in the minimal
      stimulation intensity needed to evoke a response, an increase in mean EPSP
      amplitude with development, and a decrease in paired-pulse facilitation. Quantal
      parameters were extracted by three separate methods including method of failures,
      coefficient of variance, and parameter optimization through noise deconvolution.
      All methods supported presynaptic mediation of facilitation. Comparison of
      quantal parameters during development indicated an increase in mean quantal
      content. 4. The results demonstrate that synaptic strength is altered over the
      course of development because of, at least in part, changes in presynaptic
      release mechanisms. Developmental differences in presynaptic function provide an
      explanation of differences in mechanisms for expression of long-term
      potentiation. The lower initial probability of transmitter release in neonates
      may permit increased presynaptic change.

PMID- 7623084
TI  - Dynamics of neurons controlling movements of a locust hind leg: Wiener kernel
      analysis of the responses of proprioceptive afferents.
AB  - 1. The response properties of proprioceptive sensory neurons providing input to
      the local circuits controlling leg movements of the locust have been analysed by
      the Wiener kernel method. The proprioceptor, the femoral chordotonal organ,
      encodes the position and movements of the tibia about the femorotibial joint. 2.
      Intracellular recordings were made from sensory neurons while the apodeme of the
      organ was moved with a band-limited Gaussian white noise signal with a cutoff
      frequency of 27, 58, or 117 Hz. To define the input-output characteristics of the
      neurons, the first- and second-order Wiener kernels were computed by a cross
      correlation between the spike response of the afferents and the white noise
      stimulus. 3. White noise stimulation elicited sustained spiking in 50 out of 54
      afferents throughout the 20 s periods of stimulation and recording. The first
      order kernels, the linear response properties, of these afferents were of six
      basic types that were dependent on the cutoff frequency of the white noise
      stimulus. These included 1) flexion-sensitive afferents that were primarily
      position sensitive irrespective of stimulus frequency, 2) flexion-sensitive
      afferents that were position sensitive at low frequencies but also coded velocity
      at higher frequencies, 3) flexion-sensitive afferents that coded velocity at all
      stimulus frequencies, 4) flexion-sensitive afferents that coded velocity at low
      stimulus frequencies but also acceleration at high frequencies, 5) extension
      sensitive afferents that coded velocity at all stimulus frequencies, and 6)
      extension-sensitive afferents that coded velocity at low stimulus frequencies and
      acceleration at high frequencies. A seventh type contained the four remaining
      afferents that adapted rapidly to the stimulus within 3-5 s. These were all
      extension-acceleration sensitive irrespective of stimulus frequency. 4. The gain
      curves (produced by Fourier transform of the 1st-order kernels) and the power
      spectra of the linear models (produced by convolving the 1st-order kernels with
      the white noise) demonstrated that responses in the position-sensitive afferents
      are representative of a constant gain low-pass filter with a cutoff frequency of
      approximately 80 Hz, whereas those in the velocity- and acceleration-sensitive
      afferents are band passed, having peaks at 80 Hz. 5. The main nonlinearity was a
      signal compression in which the diagonal peak(s) of the second-order nonlinear
      kernels offset one or more peaks of the first-order kernels and represents a
      rectification or directional sensitivity of the afferents.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 7623085
TI  - Nonspiking local interneurons in insect leg motor control. I. Common layout and
      species-specific response properties of femur-tibia joint control pathways in
      stick insect and locust.
AB  - 1. Locusts (Locusta migratoria) and stick insects (Carausius morosus) exhibit
      different strategies for predator avoidance. Locusts rely primarily on walking
      and jumping to evade predators, whereas stick insects become cataleptic,
      catalepsy forming a major component of the twig mimesis exhibited by this
      species. The neuronal networks that control postural leg movements in locusts and
      stick insects are tuned differently to their specific behavioral tasks. An
      important prerequisite for the production of catalepsy in the stick insect is the
      marked velocity dependency of the control network, which appears to be generated
      at the level of nonspiking local interneurons. We examined interneuronal pathways
      in the network controlling the femur-tibia joint of the locust middle leg and
      compared its properties with those described for the stick insect middle leg. It
      was our aim to identify possible neural correlates of the species-specific
      behavior with regard to postural leg motor control. 2. We obtained evidence that
      the neuronal networks that control the femur-tibia joints in the two species
      consist of morphologically and physiologically similar--and thus probably
      homologous--interneurons. Qualitatively, these interneurons receive the same
      input from the femoral chordotonal organ receptors and they drive the same pools
      of leg motoneurons in both species. 3. Pathways that contribute to the control of
      the femur-tibia joint include interneurons that support both "resisting" and
      "assisting" responses with respect to the motoneuron activity that is actually
      elicited during reflex movements. Signal processing via parallel, antagonistic
      pathways therefore appears to be a common principle in insect leg motor control.
      4. Differences between the two insect species were found with regard to the
      processing of velocity information provided by the femoral chordotonal organ.
      Interneuronal pathways are sensitive to stimulus velocity in both species.
      However, in the locust there is no marked velocity dependency of the
      interneuronal responses, whereas in the same interneurons of the stick insect it
      is pronounced. This characteristic was maintained at the level of the motoneurons
      controlling the femur-tibia joint. Pathways for postural leg motor control in the
      locust thus lack an important prerequisite for the generation of catalepsy, that
      is, a marked velocity dependency.

PMID- 7623086
TI  - Nonspiking local interneurons in insect leg motor control. II. Role of nonspiking
      local interneurons in the control of leg swing during walking.
AB  - 1. Nonspiking local interneurons (NSIs) were recorded intracellularly in the
      mesothoracic ganglion of semi-intact locusts walking on a treadwheel.
      Interneurons were characterized by their connectivity to motoneurons. Their
      activity patterns in the step cycle and the effect current injection had on the
      leg movement were analyzed. We examined interneurons that provided excitatory or
      inhibitory synaptic drive to a subset of motoneurons active during the swing
      movement of walking. 2. Interneuron activity was observed to support or oppose
      the actual leg movement. Both supporting and opposing interneurons were active
      simultaneously, lending support to the idea that the actual motor output of
      walking is generated by the adjustment of parallel antagonistic pathways of
      signal processing. 3. The examined interneurons showed qualitatively the same
      patterns of activity during forward and backward walking. This indicates that
      swing movement in both situations may be generated by similar neuronal networks
      (although the mechanism of movement reversal remains unclear). 4. At least two
      functional types of NSIs could be distinguished. First, there were interneurons
      whose depolarization patterns showed distinct variability, often correlated with
      duration or amplitude of the swing movement. As a rule, current injection had
      minor, if any, effects on leg movement. Populations of these interneurons appear
      to be involved in the control of a coordinated swing movement by driving
      appropriate sets of muscle groups. The second type of NSIs showed more
      stereotyped activity patterns that varied relatively little with changes in the
      swing movement. Current injection had strong effects on the leg movement and
      could, for example, arrest the leg in the stance phase. These interneurons appear
      to be primarily involved in the trigger mechanism of leg swing.

PMID- 7623087
TI  - Monaural inhibition in cat auditory cortex.
AB  - 1. Several studies of auditory cortex have examined the competitive inhibition
      that can occur when appropriate sounds are presented to each ear. However, most
      cortical neurons also show both excitation and inhibition in response to
      presentation of stimuli at one ear alone. The extent of such inhibition has not
      been described. Forward masking, in which a variable masking stimulus was
      followed by a fixed probe stimulus (within the excitatory response area), was
      used to examine the extent of monaural inhibition for neurons in primary auditory
      cortex of anesthetized cats (barbiturate or barbiturate-ketamine). Both the
      masking and probe stimuli were 50-ms tone pips presented to the contralateral
      ear. Most cortical neurons showed significant forward masking at delays beyond
      which masking effects in the auditory nerve are relatively small compared with
      those seen in cortical neurons. Analysis was primarily concerned with such
      components. Standard rate-level functions were also obtained and were examined
      for nonmonotonicity, an indication of level-dependent monaural inhibition. 2.
      Consistent with previous reports, a wide range of frequency tuning properties
      (excitatory response area shapes) was found in cortical neurons. This was matched
      by a wide range of forward-masking-derived inhibitory response areas. At the most
      basic level of analysis, these were classified according to the presence of
      lateral inhibition, i.e., where a probe tone at a neuron's characteristic
      frequency was masked by tones outside the limits of the excitatory response area.
      Lateral inhibition was a property of 38% of the sampled neurons. Such neurons
      represented 77% of those with nonmonotonic rate-level functions, indicating a
      strong correlation between the two indexes of monaural inhibition; however, the
      shapes of forward masking inhibitory response areas did not usually correspond
      with those required to account for the "tuning" of a neuron. In addition, it was
      found that level-dependent inhibition was not added to by forward masking
      inhibition. 3. Analysis of the discharges to individual stimulus pair
      presentations, under conditions of partial masking, revealed that discharges to
      the probe occurred independently of discharges to the preceding masker. This
      indicates that even when the masker is within a neuron's excitatory response
      area, forward masking is not a postdischarge habituation phenomenon. However, for
      most neurons the degree of masking summed over multiple stimulus presentations
      appears determined by the same stimulus parameters that determine the probability
      of response to the masker.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7623088
TI  - Sodium channel inactivation is impaired in equine hyperkalemic periodic
      paralysis.
AB  - 1. Equine hyperkalemic periodic paralysis (E-HPP) is a dominantly inherited
      disorder of muscle that causes recurrent episodes of stiffness (myotonia) and
      weakness in association with elevated serum K+. Affected horses carry a mutant
      allele of the skeletal muscle isoform of the Na channel alpha-subunit. To
      understand how this mutation may cause the disease phenotype, the functional
      defect in Na channel behavior was defined physiologically by recording unitary
      currents from cell-attached patches on normal and affected equine myotubes. 2.
      The presence of the mutation was confirmed in our cell line by restriction digest
      of polymerase chain reaction (PCR)-amplified genomic DNA. Myotubes from the
      affected horse were heterozygous for the point mutation that codes for a Phe to
      Leu substitution in S3 of domain IV. This assay provides a rapid technique to
      screen for the mutation in horses at risk. 3. The primary physiological defect in
      mutant Na channels was an impairment of inactivation. This defect was manifest as
      bursts of persistent activity during which the channel closed and reopened
      throughout a maintained depolarization. Disrupted inactivation slowed the decay
      of the ensemble-averaged current and produced an eightfold increase in the steady
      state open probability measured at the end of a 40-ms pulse. This point mutation
      identifies a new region of the alpha subunit that is important for rapid
      inactivation of the channel. 4. The persistent Na current was produced by a
      distinct mode of gating. Failure of a mutant channel to inactivate was infrequent
      and occurred in groups of consecutive trials.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7623089
TI  - Analysis of short-latency reflexes in human elbow flexor muscles.
AB  - 1. A motor and digital controller have been developed to apply rapid stretches to
      the human elbow joint. The digital controller returns the forearm to the initial
      position before the reflex contraction. Thus short-latency reflex responses can
      be cleanly separated in time from the mechanical effects of the stretch under a
      wide variety of loading conditions. 2. The reflex force varies linearly with the
      velocity of stretch over nearly 2 orders of magnitude. The reflex force also
      varies linearly with the tonic level of force over the entire range of forces
      studied (0-100 N). This contrasts sharply with, for example, the human ankle
      joint, which shows a very limited linear range. 3. As the digital controller is
      made more compliant (less stiff), reflex shortening increases dramatically and
      becomes more prolonged, whereas the reflex force becomes somewhat smaller and
      shorter. With compliant loads and the brief stretches we applied, the reflex
      shortening is approximately equal to the stretch that generated it. 4.
      Simulations of the results confirm that the dependence of reflex shortening and
      force on the stiffness of the load is mainly determined by the mechanics of the
      limb and muscles. The simulations also indicate that 1) the gain of the reflex is
      as high as it can be without causing instability and 2) the presence of a
      rectification nonlinearity (e.g., lengthening the muscle produces a reflex, but
      shortening the muscle does not) is mainly responsible for preserving the
      stability of the elbow system.

PMID- 7623090
TI  - Control of locomotion in marine mollusk Clione limacina. VIII. Cerebropedal
      neurons.
AB  - 1. The pteropod mollusk Clione limacina swims by rhythmical oscillations of two
      wings, and its spatial orientation during locomotion is determined by tail
      movements. The majority of neurons responsible for generation of the wing and
      tail movements are located in the pedal ganglia. On the other hand, the majority
      of sensory inputs that affect wing and tail movements project to the cerebral
      ganglia. The goal of the present study was to identify and characterize
      cerebropedal neurons involved in the control of the swimming central generator or
      motor neurons of wing and tail muscles. Cerebropedal neurons affecting locomotion
      controlling mechanisms are located in the rostromedial (CPA neurons), caudomedial
      (CPB neurons), and central (CPC neurons) zones of the cerebral ganglia. According
      to their morphology and effects on pedal mechanisms, 10 groups of the
      cerebropedal neurons can be distinguished. 2. CPA1 neurons project through the
      ipsilateral cerebropedal connective to both pedal ganglia. Activation of a CPA1
      by current injection resulted in speeding up of the locomotor rhythm and
      intensification of the firing of the locomotor motor neurons. 3. CPA2 neurons
      send numerous thin fibers into the ipsi- and contralateral pedal and pleural
      ganglia through the cerebropedal and cerebropleural connectives. They strongly
      inhibit the wing muscle motor neurons and, to a lesser extent, slow down the
      locomotor rhythm. 4. CPB1 neurons project through the contralateral cerebropedal
      connective to both pedal ganglia. They activate the locomotor generator. 5. CPB2
      neurons also project, through the contralateral cerebropedal connective, to both
      pedal ganglia. They affect wing muscle motor neurons. 6. CPB3 neurons have
      diverse morphology: they project to the pedal ganglia either through the
      ipsilateral cerebropedal connective, or through the contralateral one, or through
      both of them. They affect putative motor neurons of the tail muscles. 7. CPC1,
      CPC2, and CPC3 neurons project through the ipsilateral cerebropedal connective to
      both pedal ganglia. They activate the locomotor generator. 8. CPC4 and CPC5
      neurons project through the contralateral cerebropedal connective to the
      contralateral pedal ganglia. They activate the locomotor generator. 9.
      Serotonergic neurons were mapped in the CNS of Clione by immunohistochemical
      methods. Location and size of cells in two groups of serotonin-immunoreactive
      neurons in the cerebral ganglia appeared to be similar to those of CPA1 and CPB1
      neurons. This finding suggests a possible mechanism for serotonin's ability to
      exert a strong excitatory action on the locomotor generator of Clione. 10. The
      role of different groups of cerebropedal neurons is discussed in relation to
      different forms of Clione's behavior in which locomotor activity is involved.

PMID- 7623092
TI  - Long-term potentiation at the apical and basal dendritic synapses of CA1 after
      local stimulation in behaving rats.
AB  - 1. We recorded the extracellular excitatory postsynaptic potentials (EPSPs) in
      CA1 in the freely behaving rats after stimulation of the apical dendritic and
      basal dendritic afferents. The apical dendritic population EPSP was negative at
      the apical dendritic layers and positive at stratum oriens and alveus. The basal
      dendritic population EPSP was negative at basal dendritic layer (stratum oriens)
      and positive at the cell body and apical dendritic layers. 2. We delivered
      various tetanic stimulus patterns in an attempt to elicit long-term potentiation
      (LTP) at the apical dendritic synapse of CA1 pyramidal cells. A 200-Hz high
      frequency train (HF) 1 s in duration was more successful than theta-frequency
      primed bursts (PBs; 1 or 4 priming pulses followed by 10 or 4 pulses at 100 Hz)
      in eliciting LTP of the apical dendritic population EPSP, recorded either
      ipsilaterally or contralaterally. 3. Tetanus applied to the apical dendritic
      afferents occasionally elicited long-term depression (LTD) at an intensity lower
      than the LTP threshold. LTD persisted to > or = 1 day after a tetanus. 4. High
      intensity tetanic stimulations often elicited hippocampal afterdischarges (ADs).
      If the AD duration was brief (< 15 s), apical dendritic LTP could follow the AD.
      However, if the AD duration was long, no apical dendritic LTP was observed.
      Tetanus that evoked an apical dendritic LTP typically evoked a short hippocampal
      AD < 15 s in duration. 5. LTP of the basal dendritic population EPSP was readily
      elicited either after an HF or a PB tetanus of low (1.5-2 times threshold)
      stimulus intensity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7623091
TI  - Control of locomotion in marine mollusk Clione Limacina. IX. Neuronal mechanisms
      of spatial orientation.
AB  - 1. When swimming freely, the pteropod mollusk Clione limacina actively maintains
      a vertical orientation, with its head up. Any deflection from the vertical
      position causes a correcting motor response, i.e., bending of the tail in the
      opposite direction, and an additional activation of the locomotor system. Clione
      can stabilize not only the vertical orientation with its head up, but also the
      posture with its head down. The latter is observed at higher water temperature,
      as well as at a certain stage of hunting behavior. The postural control is absent
      in some forms of behavior (vertical migrations, defensive reactions, "looping"
      when hunting). The postural reflexes are driven by input from the statocysts.
      After removal of the statocysts, Clione was unable to maintain any definite
      spatial orientation. 2. Activity of the neuronal mechanisms controlling spatial
      orientation of Clione was studied in in vitro experiments, with the use of a
      preparation consisting of the CNS and statocysts. Natural stimulation (tilt of
      the preparation up to 90 degrees) was used to characterize responses in the
      statocyst receptor cells (SRCs). It was found that the SRCs depolarized and fired
      (10-20 Hz) when, during a tilt, they were in a position on the bottom part of the
      statocyst, under the statolith. Intracellular staining has shown that the SRC
      axons terminate in the medial area of the cerebral ganglia. Electrical
      connections have been found between some of the symmetrical SRCs of the left and
      right statocysts. 3. Gravistatic reflexes were studied by using both natural
      stimulation (tilt of the preparation) and electrical stimulation of SRCs. The
      reflex consisted of three components: 1) activation of the locomotor rhythm
      generator located in the pedal ganglia; this effect of SRCs is mediated by
      previously identified CPA1 and CPB1 interneurons that are located in the cerebral
      ganglia and send axons to the pedal ganglia; 2) bending the tail evoked by
      differential excitation and inhibition of different groups of tail muscle motor
      neurons; this effect is mediated by CPB3 interneurons; and 3) modification of
      wing movements by differential excitation and inhibition of different groups of
      wing motor neurons; this effect is mediated by CPB2 interneurons. 4. Gravistatic
      reflexes in the tail motor neurons were inhibited or reversed at a higher water
      temperature. 5. The SRCs are not "pure" gravitation sensory organs because they
      are subjected to strong influences from the CNS. In particular, CPC1
      interneurons, participating in coordination of different aspects of the hunting
      behavior, exert an excitatory action on some of the SRCs, and inhibitory actions
      on others.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7623093
TI  - Bipedal reflex coordination to tactile stimulation of the sural nerve during
      human running.
AB  - 1. Cutaneous reflex responses were elicited during human running (8 km/h) on a
      treadmill by electrical stimulation of the sural nerve at the ankle. Stimulus
      trains (5 pulses of 1 ms at 200 Hz) at three nonnociceptive intensities, which
      were 1.5, 2.0, and 2.5 times perception threshold (PT), were delivered at 16
      phases of the step cycle. For 11 subjects the surface electromyographic (EMG)
      activity of both the ipsilateral and contralateral long head of the biceps
      femoris (iBF and cBF, respectively), the semitendinosus (iST and cST), the rectus
      femoris (iRF and cRF), and the tibialis anterior (iTA and cTA) were recorded. 2.
      During human running nonnociceptive sural nerve stimulation appears to be
      sufficient to elicit large, widespread and statistically significant reflex
      responses, with a latency of approximately 80 ms and a duration of approximately
      30 ms. These reflex responses seem to be an elementary property of human
      locomotion. This is indicated by the occurrence of the responses in all subjects,
      the consistency of most of the reflex patterns across the subjects and, apart
      from a small amount of habituation, the reproducibility of the responses during
      the course of the experiment. 3. The responses are modulated continuously
      throughout the step cycle such that their magnitude does not in general covary
      with the background locomotor activities. This is observed most clearly in iST,
      iTA, and cTA for which statistically significant reflex reversals are
      demonstrated, and in cRF and cTA for which the responses are gated during most of
      the step cycle. 4. The response magnitude generally increases as a function of
      increasing intensity, whereas the phase-dependent reflex modulation is intensity
      independent. 5. A functional dissociation within the ipsilateral hamstring
      muscles is demonstrated: the iBF and iST show an antagonistic reflex pattern
      (facilitatory and suppressive, respectively) during the periods of synergistic
      background locomotor activity in the step cycle. Contralaterally, however, the
      cBF and cST are reflexively activated as close synergists during these periods.
      6. The reflex responses and their phase-dependent modulation are different for
      the homologous muscles in the two legs. Yet, some similarities are observed.
      These are present rather with respect to the phase of the corresponding leg than
      with respect to the phase of the stimulated leg. Both observations suggest that
      the phase-dependent reflex modulation is controlled separately in the ipsilateral
      and contralateral legs. 7. The response simultaneity in all investigated muscles
      supports the notion of a coordinated cutaneous interlimb reflex during human
      running.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7623094
TI  - Block of multiple presynaptic calcium channel types by omega-conotoxin-MVIIC at
      hippocampal CA3 to CA1 synapses.
AB  - 1. The effect of the voltage-dependent Ca channel (VDCC) antagonist omega
      conotoxin-MVIIC (omega-CTx-MVIIC) on the presynaptic Ca influx and synaptic
      transmission was studied in area CA1 of guinea pig hippocampus. The presynaptic
      Ca transient ([Ca]t) and the field excitatory postsynaptic potential (fEPSP)
      evoked by a single electrical stimulus were simultaneously recorded at CA3 to CA1
      synapses. 2. omega-CTx-MVIIC dose dependently blocked the fEPSP and the
      presynaptic [Ca]t without affecting the presynaptic fiber volley and the
      presynaptic resting Ca level. During application of omega-CTx-MVIIC, the decrease
      of both the fEPSP and the presynaptic [Ca]t had a similar time course, and the
      initial slope of the fEPSP is proportional to about the fourth power of the
      amplitude of the presynaptic [Ca]t. These results strongly suggest that omega-CTx
      MVIIC inhibits the fEPSP by blocking presynaptic Ca channels at hippocampal CA3
      to CA1 synapses. 3. Sequential application of high concentrations of omega-CTx
      MVIIC (10 microM) and other VDCC blockers including omega-conotoxin-GVIA (omega
      CTx-GVIA, 1 microM) and omega-agatoxin-IVA (omega-Aga-IVA, 1 microM) showed that
      omega-CTx-MVIIC significantly occludes the effects of omega-CTx-GVIA and omega
      Aga-IVA. Combined application of omega-CTx-GVIA (1 microM) and omega-Aga-IVA (1
      microM) largely but not completely occluded the effect of omega-CTx
      MVIIC.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7623095
TI  - Trisynaptic inhibition from the contralateral vertical semicircular canal nerves
      to neck motoneurons mediated by spinal commissural neurons.
AB  - 1. Neck motoneurons usually receive disynaptic excitation and inhibition from
      individual semicircular canal nerves. However, in motoneurons of some neck
      muscles, trisynaptic inhibition is evoked by stimulation of the contralateral
      vertical canal nerves. The present study was performed to analyze this pathway
      and the location and properties of the last-order interneurons responsible for
      mediating this trisynaptic inhibition from the contralateral vertical canal
      nerves to neck motoneurons in anesthetized cats. 2. Bipolar stimulating
      electrodes were implanted on the contralateral anterior (ACN), lateral (LCN), and
      posterior canal nerve (PCN), and postsynaptic potentials (PSPs) evoked by
      electrical stimulation of individual canal nerves were intracellularly recorded
      from motoneurons of the obliquus capitis inferior (OCI), longus capitis (LC), and
      rectus capitis posterior (RCP) muscles. Stimulation of the contralateral ACN
      evoked trisynaptic inhibitory PSPs (IPSPs) in OCI and LC motoneurons and
      disynaptic excitatory PSPs (EPSPs) in RCP motoneurons. Stimulation of the
      contralateral PCN evoked di- and trisynaptic IPSPs in OCI and RCP motoneurons and
      disynaptic EPSPs in LC motoneurons. Stimulation of the contralateral LCN evoked
      disynaptic EPSPs in all of the motoneurons examined. 3. To determine the pathway
      that mediates these trisynaptic IPSPs from the vertical canal nerves to neck
      motoneurons, a lesion was made in the lower medulla, and the patterns of PSPs
      evoked by stimulation of the three contralateral canal nerves were compared
      before and after the lesion. Interruption of the ipsilateral medial longitudinal
      fascicle (MLF) abolished all disynaptic EPSPs and IPSPs from the three
      contralateral canal nerves in OCI, LC, and RCP motoneurons. In contrast,
      trisynaptic IPSPs evoked by stimulation of the contralateral ACN or PCN remained
      unaffected by sectioning the MLFs bilaterally. Sectioning of the contralateral
      lateral vestibulospinal tract (LVST) eliminated the trisynaptic IPSPs in OCI and
      LC motoneurons evoked by contralateral ACN stimulation and trisynaptic IPSPs in
      OCI and RCP motoneurons evoked by contralateral PCN stimulation but did not
      affect disynaptic EPSPs and IPSPs. 4. Stimulation of the contralateral LVST in
      the lower medulla after sectioning the bilateral MLFs evoked disynaptic IPSPs in
      OCI, LC, and RCP motoneurons. Because the LVST only projects ipsilaterally, this
      finding indicates that the last-order interneurons that mediate the trisynaptic
      inhibition through the LVST are most likely commissural neurons located in the
      spinal cord. 5. To determine the locations of last-order commissural neurons
      terminating on OCI motoneurons, wheat germ agglutinin conjugated to horseradish
      peroxidase (WGA-HRP) was injected into the OCI muscle nerve at C1.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7623096
TI  - Neurons in the monkey superior colliculus predict the visual result of impending
      saccadic eye movements.
AB  - 1. Previous experiments have shown that visual neurons in the lateral
      intraparietal area (LIP) respond predictively to stimuli outside their classical
      receptive fields when an impending saccade will bring those stimuli into their
      receptive fields. Because LIP projects strongly to the intermediate layers of the
      superior colliculus, we sought to demonstrate similar predictive responses in the
      monkey colliculus. 2. We studied the behavior of 90 visually responsive neurons
      in the superficial and intermediate layers of the superior colliculus of two
      rhesus monkeys (Macaca mulatta) when visual stimuli or the locations of
      remembered stimuli were brought into their receptive fields by a saccade. 3.
      Thirty percent (18/60) of intermediate layer visuomovement cells responded
      predictively before a saccade outside the movement field of the neuron when that
      saccade would bring the location of a stimulus into the receptive field. Each of
      these neurons did not respond to the stimulus unless an eye movement brought it
      into its receptive field, nor did it discharge in association with the eye
      movement unless it brought a stimulus into its receptive field. 4. These neurons
      were located in the deeper parts of the intermediate layers and had relatively
      larger receptive fields and movement fields than the cells at the top of the
      intermediate layers. 5. The predictive responses of most of these neurons (16/18,
      89%) did not require that the stimulus be relevant to the monkey's rewarded
      behavior. However, for some neurons the predictive response was enhanced when the
      stimulus was the target of a subsequent saccade into the neuron's movement field.
      6. Most neurons with predictive responses responded with a similar magnitude and
      latency to a continuous stimulus that remained on after the saccade, and to the
      same stimulus when it was only flashed for 50 ms coincident with the onset of the
      saccade target and thus never appeared within the cell's classical receptive
      field. 7. The visual response of neurons in the intermediate layers of the
      colliculus is suppressed during the saccade itself. Neurons that showed
      predictive responses began to discharge before the saccade, were suppressed
      during the saccade, and usually resumed discharging after the saccade. 8. Three
      neurons in the intermediate layers responded tonically from stimulus appearance
      to saccade without a presaccadic burst. These neurons responded predictively to a
      stimulus that was going to be the target for a second saccade, but not to an
      irrelevant flashed stimulus. 9. No superficial layer neuron (0/27) responded
      predictively when a stimulus would not be brought into their receptive fields by
      a saccade.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7623097
TI  - Antigen-induced long-term potentiation of nicotinic synaptic transmission in the
      superior cervical ganglion of the guinea pig.
AB  - 1. Recordings of evoked postganglionic compound action potentials (CAPs) evoked
      by preganglionic stimulation were obtained from guinea pig superior cervical
      ganglia (SCGs) in vitro to study the effects of specific antigen challenge on
      ganglionic synaptic transmission. SCGs were removed from guinea pigs actively
      sensitized to ovalbumin. 2. Exposing SCGs from sensitized animals to the
      sensitizing antigen (0.01-10 micrograms/ml) for 5 min produced a sustained
      increase in the magnitude of the evoked CAP unaccompanied by a change in the
      preganglionic volley. Nonsensitizing antigens were ineffective. Also ineffective
      were antigens applied to nonsensitized SCG. This persistent antigen-induced
      increase in synaptic transmission was designated antigen-induced long-term
      potentiation (LTP) (A-LTP) because its duration (> 30 min) greatly outlasted
      posttetanic potentiation (PTP) in this ganglion. 3. A-LTP and neurogenic LTP (N
      LTP) were observed to coexist in the same ganglion; the presence of one form of
      synaptic plasticity did not preclude the development of the other. Both phenomena
      were influenced by presynaptic factors: prolonged (2 h, 40 Hz) repetitive
      presynaptic stimulation abolished A-LTP or N-LTP but did not affect PTP. 4. By
      contrast to N-LTP, which requires a brief presynaptic tetanus, A-LTP could be
      triggered over a wide range of presynaptic stimulation (0.016-3 Hz) or even in
      the absence of presynaptic stimulation. 5. The amplitude and duration of A-LTP
      were not significantly affected by 1) H1, H2, or H3 histamine receptor
      antagonists added before or after antigen challenge; 2) the presence of
      saturating concentrations of histamine (100-300 microM); 3) the presence of
      specific or nonspecific lipoxygenase inhibitors or a selective cyclooxygenase
      inhibitor; or 4) blockade of alpha- or beta-adrenergic receptors, 5-HT3
      receptors, muscarinic receptors, or glutamate receptors, or inhibition of
      acetylcholinesterase or protein synthesis. 6. Our results indicate that specific
      antigen challenge of isolated sympathetic ganglia activates resident mast cells
      to release substances that initiate a novel form of synaptic plasticity, an
      activity-independent and long-lasting increase in synaptic efficacy.

PMID- 7623098
TI  - Salamander olfactory bulb neuronal activity observed by video rate, voltage
      sensitive dye imaging. II. Spatial and temporal properties of responses evoked by
      electric stimulation.
AB  - 1. Video imaging of changes in voltage-sensitive dye (VSD) fluorescence was used
      to analyze spatial and temporal properties of activity patterns in the in vivo
      salamander olfactory bulb and primordium piriform cortex after electric
      stimulation. Distribution of activity among and within the neuronal layers was
      analyzed after orthodromic stimulation of the whole olfactory nerve (ON),
      isolated fascicles, or local epithelial sites, and after antidromic stimulation
      of the medial olfactory tract (OT). 2. Optical signals propagated through the
      bulbar layers with a sequence that correlates with electrophysiological
      responses. After orthodromic stimulation, VSD responses started in the glomerular
      layer, spread to the deeper laminae, and, after reaching the region of
      mitral/tufted somata, were observed as a brief burst of activity in the OT.
      Compound action potentials in the ON were associated with short-duration, rapidly
      depolarizing optical responses in the ON layer. Responses in glomerular layer and
      external plexiform layer (EPL) first showed in some recordings a brief, small
      amplitude hyperpolarization, followed by a period of depolarization, followed by
      a second, longer-lasting hyperpolarization. The periods of optical
      hyperpolarization could be related to events observed in intracellular
      mitral/tufted cell recordings. 3. With shocks delivered to the entire ON,
      depolarizing responses were nonhomogeneously distributed, appearing as multiple
      foci or bands of activity. Spatial patterns within each bulbar layer had poorly
      defined borders. Sites showing short-latency responses were often those with the
      largest and longest-lasting activity. 4. Increasing the intensity of stimulation
      to the ON enhanced the size and duration of the depolarizing and hyperpolarizing
      responses. The short-latency, early hyperpolarization was best seen with low
      intensity, peripherally placed stimuli. 5. ON stimulation also elicited activity
      in the contralateral bulb. Activity started at the innermost layers and spread in
      patches to regions of the EPL just beneath the glomeruli. These had durations
      similar to ipsilateral responses, but longer latencies. A period of early
      hyperpolarization, longer than that on the ipsilateral side, was followed by
      prolonged depolarization and then by a second, later hyperpolarization. 6.
      Antidromic stimuli applied to the OT evoked optical responses consisting of a
      period of depolarization followed by hyperpolarization, similar to the components
      elicited by orthodromic stimuli. These responses had short time courses, began in
      the deeper layers, and spread to the superficial region of the bulb usually
      without reaching the glomerular region. 7. Punctate stimulation of the mucosa or
      nerve elicited depolarizing and hyperpolarizing events that depended on the
      stimulation site.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7623099
TI  - Coherent spatiotemporal patterns of ongoing activity revealed by real-time
      optical imaging coupled with single-unit recording in the cat visual cortex.
AB  - 1. We examined the spatiotemporal organization of ongoing activity in cat visual
      areas 17 and 18, in relation to the spontaneous activity of individual neurons.
      To search for coherent activity, voltage-sensitive dye signals were correlated
      with the activity of single neurons by the use of spike-triggered averaging. In
      each recording session an area of at least 2 x 2 mm of cortex was imaged, with
      124 diodes. In addition, electrical recordings from two isolated units, the local
      field potential (LFP) from the same microelectrodes, and the surface
      electroencephalogram (EEG) were recorded simultaneously. 2. The optical signals
      recorded from the dye were similar to the LFP recorded from the same site.
      Optical signals recorded from different cortical sites exhibited a different time
      course. Therefore real-time optical imaging provides information that is
      equivalent in many ways to multiple-site LFP recordings. 3. The spontaneous
      firing of single neurons was highly correlated with the optical signals and with
      the LFP. In 88% of the neurons recorded during spontaneous activity, a
      significant correlation was found between the occurrence of a spike and the
      optical signal recorded in a large cortical region surrounding the recording
      site. This result indicates that spontaneous activity of single neurons is not an
      independent process but is time locked to the firing or to the synaptic inputs
      from numerous neurons, all activated in a coherent fashion even without a sensory
      input. 4. For the cases showing correlation with the optical signal, 27-36% of
      the optical signal during spike occurrence was directly related to the occurrence
      of spontaneous spikes in a single neuron, over an area of 2 x 2 mm. In the same
      cortical area, 43-55% of the activity was directly related to the visual
      stimulus. 5. Surprisingly, we found that the amplitude of this coherent ongoing
      activity, recorded optically, was often almost as large as the activity evoked by
      optimal visual stimulation. The amplitude of the ongoing activity that was
      directly and reproducibly related to the spontaneous spikes of a single neuron
      was, on average, as high as 54% of the amplitude of the visually evoked response
      that was directly related to optimal sensory stimulation, recorded optically. 6.
      Coherent activity was detected even at distant cortical sites up to 6 mm
      apart.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7623100
TI  - Mechanosensitive currents in putative aortic baroreceptor neurons in vitro.
AB  - 1. Whole cell patch-clamp experiments were conducted to determine whether rat
      aortic baroreceptor neurons contain mechano-sensitive conductances. 2. Putative
      aortic baroreceptor neurons in the nodose ganglia were identified by injecting
      DiI onto the adventitia of the aortic arch. Nodose ganglia neurons were
      dissociated after > or = 1 wk. A fluorescein-conjugated tetanus toxin fragment
      was used to confirm that the cells labeled with DiI in culture were neurons. 3.
      Hypoosmotic stretch significantly increased the conductance of DiI-labeled
      neurons (n = 19). The reversal potential of the response was -11 +/- 1 (SE) mV.
      4. In experiments on unlabeled neurons, only 7 of 13 cells showed increases in
      conductance. BC3H1 cells, a mouse tumor cell line, showed no changes in
      conductance. 5. Gadolinium (20 microM), a putative blocker of mechanosensitive
      channels, prevented the increase in conductance produced by hypoosmolality in
      seven of seven labeled cells. Equimolar concentrations of lanthanum (n = 6) and
      omega-conotoxin GVIA (1 microM, n = 4), which block voltage-gated calcium
      channels, failed to significantly affect the inward current.

PMID- 7623101
TI  - Alpha-subunit of calcium/calmodulin-dependent protein kinase II enhances gamma
      aminobutyric acid and inhibitory synaptic responses of rat neurons in vitro.
AB  - 1. Here we report that in acutely isolated rat spinal dorsal horn neurons, the
      gamma-aminobutyric acid-A (GABAA) receptor can be regulated by calcium/calmodulin
      dependent protein kinase II (CaM-KII). Intracellularly applied, the alpha-subunit
      of CaM-KII enhanced GABAA-receptor-activated current recorded with the use of the
      whole cell patch-clamp technique. This effect was associated with reduced
      desensitization of GABA responses. 2. GABA-induced currents are also potentiated
      by calyculin A, an inhibitor of protein phosphatases 1 and 2A. 3. Conventional
      intracellular recordings were made from hippocampal CA1 neurons in slices to
      determine the effect of intracellular application of CaM-KII on inhibitory
      synaptic potentials evoked by electrical stimulation of the stratum
      oriens/alveus. The inhibitory synaptic potential was enhanced by CaM-KII; this
      mechanism may contribute to long-term enhancement of inhibitory synaptic
      transmission and may also play a role in other forms of plasticity in the
      mammalian brain.

PMID- 7623102
TI  - High extracellular potassium, and not extracellular glutamate, is required for
      the propagation of spreading depression.
AB  - 1. Cortical spreading depression (SD) is a propagating transient suppression of
      electrical activity associated with depolarization, which may contribute to the
      pathophysiology of important neurological disorders, including cerebral ischemia
      and migraine. The purpose of this study is to ascertain whether SD propagation
      depends on local accumulation of extracellular K+ or glutamate. 2. Propagating SD
      recorded through microdialysis probes perfused with artificial cerebrospinal
      fluid (ACSF) was much smaller than that recorded with conventional glass
      microelectrodes, presumably because some SD-induced transient changes in the
      extracellular fluid composition were buffered by ACSF. We have exploited this
      effect to determine whether perfusion with a medium containing increasing amounts
      of K+ and/or glutamate favors SD propagation. 3. Increasing the concentration of
      K+ (15-60 mmol/l) in the perfusion medium dose-dependently restored SD
      propagation, whereas application of 100-250 mumol/l glutamate through the
      microdialysis probe had no effect. Superimposing 200 mumol/l glutamate onto 15
      and 30 mmol/l K+ did not further improve the restoration of SD propagation by K+.
      4. Because potent uptake mechanisms may efficiently clear exogenous glutamate
      from the extracellular space, the effect of local inhibition of high-affinity
      glutamate uptake was also studied. Perfusion of the recording microdialysis probe
      with 1 mmol/l L-trans-pyrrolidine-2,4-dicarboxylate (L-trans-PDC), either alone
      or together with 200 mumol/l glutamate, had no effect. In addition, L-trans-PDC
      did not potentiate the positive effect of 30 mmol/l K+ on SD propagation. 5.
      These results strongly suggest that high extracellular K+, and not extracellular
      glutamate, is the driving force sustaining SD propagation.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7623103
TI  - Single-unit activity in the primate nucleus reticularis tegmenti pontis related
      to vergence and ocular accommodation.
AB  - 1. In the present study we used single-unit recording techniques in alert rhesus
      monkeys to investigate a precerebellar nucleus, the nucleus reticularis tegmenti
      pontis (NRTP), for neurons related to vergence and ocular accommodation. 2. In
      the medial NRTP, we identified 32 cells with activity that linearly increased
      with increases in the amplitude of the near response and 33 cells with activity
      that linearly increased with increases in the amplitude of the far response.
      These near and far response neurons were often encountered close to neurons
      displaying saccade-related activity, but their activity was related neither to
      saccadic nor to smooth pursuit eye movements. Micro-stimulation at the site of
      near or far response neurons often produced changes in vergence angle and
      accommodation. 3. The NRTP is known to receive cortical afferents and to have
      reciprocal connections with the cerebellum; therefore it is likely that the near
      and far response neurons in the medial NRTP form part of a cerebropontocerebellar
      pathway modulating or controlling vergence and ocular accommodation.

PMID- 7623104
TI  - Two functionally different synergies during arm reaching movements involving the
      trunk.
AB  - 1. To address the problem of the coordination of a redundant number of degrees of
      freedom in motor control, we analyzed the influence of voluntary trunk movements
      on the arm endpoint trajectory during reaching. 2. Subjects made fast
      noncorrected planar movements of the right arm from a near to a far target
      located in the ipsilateral work space at a 45 degrees angle to the sagittal
      midline of the trunk. These reaching movements were combined with a forward or a
      backward sagittal motion of the trunk. 3. The direction, positional error,
      curvature, and velocity profile of the endpoint trajectory remained invariant
      regardless of trunk movements. Trunk motion preceded endpoint motion by
      approximately 175 ms, continued during endpoint movement to the target, and
      outlasted it by 200 ms. This sequence of trunk and arm movements was observed
      regardless of the direction of the endpoint trajectory (to or from the far
      target) or trunk movements (forward or backward). 4. Our data imply that reaching
      movements result from two control synergies: one coordinates trunk and arm
      movements leaving the position of the endpoint unchanged, and the other produces
      interjoint coordination shifting the arm endpoint to the target. The use of
      functionally different synergies may underlie a solution of the redundancy
      problem.

PMID- 7623105
TI  - Acetylcholine excites GABAergic neurons of the ferret perigeniculate nucleus
      through nicotinic receptors.
AB  - 1. The actions of acetylcholine (ACh) on the GABAergic neurons of the
      perigeniculate nucleus (PGN) were investigated with the use of extra- and
      intracellular recording techniques in spontaneously spindling ferret thalamic
      slices maintained in vitro. 2. Local application of ACh to PGN neurons resulted
      in rapid depolarization followed by a longer lasting hyperpolarization. Neither
      of these responses were abolished by blockade of synaptic transmission with
      tetrodotoxin (TTX) nor with low Ca2+ and elevated Mg2+ solution, indicating that
      they are direct postsynaptic actions of ACh on PGN cells. Functionally, the rapid
      depolarizing response could activate both single spike activity, as well as low
      threshold Ca2+ spike-mediated bursts. 3. The fast depolarizing response to ACh
      was selectively blocked by application of the nicotinic antagonist hexamethonium,
      whereas the slow hyperpolarizing response to ACh was selectively blocked by
      application of the muscarinic antagonist (-)scopolamine. Application of both
      hexamethonium and (-)scopolamine blocked the modulation of PGN action-potential
      firing by ACh. 4. Local application of the nicotinic agonist 1,1-dimethyl-4
      phenylpiperazinium (DMPP) resulted in a depolarizing response and an increase in
      membrane conductance, whereas application of the muscarinic agonist DL-muscarine
      chloride resulted in a hyperpolarizing response and an increase in membrane
      conductance. When applied to spontaneously spindling PGN cells, both DMPP and DL
      muscarine blocked the occurrence of spindle oscillations. However, only DMPP was
      associated with depolarization and the generation of single spike activity. 5.
      These results indicate that the GABAergic cells of the PGN possess postsynaptic
      nicotinic as well as muscarinic receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7623106
TI  - Developmental determinants at the mammalian optic chiasm.
AB  - The mammalian optic chiasm is widely and properly regarded as a region where
      axons from the temporal retina take an uncrossed course and separate from axons
      arising in the nasal retina that take a crossed course. However, this is but a
      rough approximation of the adult situation, and developmental studies must take
      account of several distinctive stages and axon rearrangements that characterize
      the region of the chiasm. At the early and late stages of development of
      nonprimate species the axons do not segregate in accordance with a strict naso
      temporal rule at all, and their behavior at the chiasm is not relevant to the
      formation of the naso-temporal division. As the axons pass from the eye to the
      chiasm they tend to lose their retinotopic order, to gain a chronotopic order,
      and then, in the region of the chiasm, to regain some aspects of the retinotopic
      order before reaching their terminal sites. Molecular or cellular cues that allow
      the several distinct organizational steps to occur must be expected in the
      retina, on the axons themselves, and also along the pathway of the axons,
      prechiasmatically and at the chiasm. Some of these cues will be associated with
      local nerve cells, some with specialized glial elements and some with the
      retinofugal axons themselves. Several candidate molecules have been identified in
      the retina and along the path of the axons, but to date no clearly defined role
      in the specific events of the pathway determination have been identified. The
      sequence of developmental processes that characterizes the formation of the optic
      chiasm provides an interesting and useful challenge to experimentalists, because
      the advancing axons can now be observed in vitro and in the living brain. The
      pattern of growth changes as development proceeds, it shows distinctive
      properties in different species and in their genetic mutants, and it can be
      readily modified by simple experimental procedures. These all provide
      opportunities for investigating the function of proposed molecular cues that act
      in the development of the chiasm.

PMID- 7623107
TI  - Development of retinal vasculature is mediated by hypoxia-induced vascular
      endothelial growth factor (VEGF) expression by neuroglia.
AB  - We have studied the role of the hypoxia-inducible angiogenic growth factor
      vascular endothelial growth factor (VEGF) in the induction and control of vessel
      growth in the developing retina of rats and cats, using in situ hybridization
      techniques. VEGF is expressed successively in two layers of neural retina, the
      innermost (axon) layer and the inner nuclear layer (INL). In the axon layer, VEGF
      is expressed transiently by astrocytes as they spread across the layer, closely
      preceding the formation of superficial vessels. In the INL, VEGF is expressed
      transiently by somas at the middle of the layer (presumably Muller cells),
      closely preceding the formation of the deep layer of retinal vessels. We propose
      that hypoxia caused by the onset of neuronal activity is detected by
      strategically located populations of neuroglia, first astrocytes, then Muller
      cells. In response they secrete VEGF, inducing formation of the superficial and
      deep layers of retinal vessels, respectively. As the vessels become patent, they
      relieve the hypoxic stimulus, so vessel formation is matched to oxygen demand.
      This hypothesis was tested experimentally in three ways. Expression of the high
      affinity flk-1 receptor for VEGF was demonstrated in newly formed retinal
      vessels, confirming that the secreted VEGF acts on the vessels, in a paracrine
      fashion. Direct hypoxic regulation of VEGF expression by macroglia was
      demonstrated in primary cultures of astrocytes and in cells of a glioma line.
      Hypoxic regulation of VEGF expression in the intact developing retina was
      demonstrated by showing that oxygen-enriched atmospheres that inhibit vessel
      formation also suppress endogenous VEGF production.

PMID- 7623108
TI  - Dopamine modulates GABAc receptors mediating inhibition of calcium entry into and
      transmitter release from bipolar cell terminals in tiger salamander retina.
AB  - Using optical recording techniques, we directly monitored pre- and postsynaptic
      calcium dynamics at bipolar cell terminals while inhibiting synaptic release with
      applied GABA and modulating inhibition with dopamine. To monitor pre-synaptic
      activity, individual bipolar cells in the retinal slice were filled with either
      fura-2 or fluo-3 through a patch electrode. Calcium entry into bipolar terminals,
      elicited by depolarization from -60 mV to 0 mV, was reduced to 36% of control in
      the presence of 200 microM bath-applied GABA. Further addition of 100 microM
      dopamine to the bath relieved the GABAergic inhibition and nearly doubled the
      calcium entry. Yet dopamine alone had no apparent direct effect upon calcium
      entry. The relief from GABAergic inhibition could be reproduced with SKF-38393, a
      dopamine D1 receptor agonist, and with forskolin, an adenylyl cyclase activator,
      suggesting that dopamine acts through a cAMP second-messenger pathway. To monitor
      transmitter release from bipolar cells, slices were loaded with fura-2AM, a
      membrane permeable form of the dye. Puffs of 110 mM KCl at bipolar dendrites
      depolarized bipolar cells and elicited calcium signals that could be monitored
      both at bipolar terminals and in postsynaptic cells. Consistent with the results
      above, GABA inhibited calcium entry at bipolar terminals and also reduced
      transmitter release, measured as a decrease in calcium entry in amacrine and
      ganglion cells. The addition of dopamine relieved this inhibition and increased
      transmitter release. Our results show the spatiotemporal correlation between the
      GABAergic inhibition of calcium entry at bipolar terminals, the resulting
      reduction in postsynaptic activity, and the relief of this inhibition with
      dopamine.

PMID- 7623109
TI  - The Brn-3 family of POU-domain factors: primary structure, binding specificity,
      and expression in subsets of retinal ganglion cells and somatosensory neurons.
AB  - A search for POU domain sequences expressed in the human retina has led to the
      identification of three closely related genes: Brn-3a, Brn-3b, and Brn-3c. The
      structure and expression pattern of Brn-3b was reported earlier (Xiang et al.,
      1993); we report here the structures and expression patterns of Brn-3a and Brn
      3c. Antibodies specific for each Brn-3 protein were generated and shown to label
      only ganglion cells in a variety of vertebrate retinas. A complex pattern of
      strongly and weakly immunolabeled ganglion cells was observed in mouse, cat, and
      monkey retinae. In mouse and cat retinae, Brn-3a and Brn-3b proteins are found in
      a large fraction of ganglion cells, whereas Brn-3c is present in fewer ganglion
      cells. In the cat retina, anti-Brn-3a immunoreactivity was strong in the small
      ganglion cells (gamma cells) and weak in the remaining ganglion cells (alpha and
      beta cells); anti-Brn-3b immunoreactivity was present in all ganglion cells; and
      anti-Brn3c immunoreactivity was confined to the small ganglion cells.
      Immunolabeling of macaque retinae following retrograde labeling from the lateral
      geniculate nucleus revealed strong anti-Brn-3a immunoreactivity in a minority of
      retrogradely labeled P-type ganglion cells, and weak Brn-3a immunoreactivity in
      all of the remaining P- and M-type ganglion cells. In the same retinae, strong
      anti-Brn-3b immunoreactivity was seen in nearly all P-type ganglion cells and
      weak immunoreactivity in nearly all M-type ganglion cells. Each of the Brn-3
      specific antibodies also labeled subsets of neurons in the dorsal root and
      trigeminal ganglia, suggesting that primary somatosensory neurons and retinal
      ganglion cells share genetic regulatory hierarchies. In vitro selection of an
      optimal DNA binding site using the Brn-3b POU domain has revealed a consensus
      [(A/G)CTCATTAA(T/C)] that is recognized by each of the Brn-3 POU domains and is
      distinct from binding sites previously described for other POU domain proteins.

PMID- 7623110
TI  - Changes in c-fos mRNA expression in rat brain during odor discrimination
      learning: differential involvement of hippocampal subfields CA1 and CA3.
AB  - Levels of c-fos mRNA were measured with in situ hybridization to test for
      behaviorally dependent changes in neuronal activity in three subdivisions of
      hippocampus and in components of the olfactory and visual systems. In rats that
      performed a well-learned nose-poke response for water reward, c-fos mRNA levels
      were broadly increased, relative to values in home cage-control rats, in visual
      cortex, superior colliculus, olfactory bulb, and, to comparable levels, regions
      CA3 and CA1 of hippocampus; hybridization was not increased in the dentate gyrus.
      In rats first trained on the nose-poke behavior and then required to discriminate
      between two odors for water reward, the increase in c-fos mRNA was generally not
      as great and was more regionally differentiated. Thus, in olfactory bulb,
      hybridization was more greatly elevated in lateral than medial fields, thereby
      exhibiting regional activation corresponding to the topographic representation of
      the predominant odor sampled in the discrimination task. In hippocampus of odor
      discrimination rats, c-fos mRNA levels were far greater in the region CA3 than
      region CA1, but remained at cage control values in stratum granulosum.
      Interestingly, c-fos mRNA levels in each hippocampal subdivision were highly
      correlated with levels in other regions (e.g., visual cortex) for home cage
      controls but not for rats in the two behavioral groups. Thus, c-fos mRNA levels
      in cage-control rats appeared to be regulated by some generalized factor acting
      throughout much of the brain (e.g., arousal), while odor-discrimination
      performance changed the pattern of expression within hippocampus, and allowed for
      a differentiated response by olfactory regions to emerge. These findings suggest
      that hippocampus possesses multiple modes of functioning and makes contributions
      to behavior that vary according to task demands.

PMID- 7623111
TI  - Neurotrophins promote maturation of developing neuromuscular synapses.
AB  - Although the effects of neurotrophins on survival and differentiation of various
      neuronal populations have been well studied, little is known about their role in
      synaptic development and function. We have investigated the long-term effects of
      neurotrophins in the maturation of neuromuscular synapses in Xenopus nerve-muscle
      cocultures. BDNF and NT-3, but not NGF, elicited significant changes in several
      properties of spontaneous synaptic currents (SSCs), indicative of more mature
      synapses. Most synapses treated by the neurotrophins exhibited a bell-shaped
      distribution of SSC amplitudes, which reflects mature quantal secretion. The
      neurotrophins also potentiated the efficacy and reliability of stimulus-induced
      synaptic transmission. Moreover, BDNF and NT-3 increased the levels of the
      synaptic vesicle proteins, synaptophysin, and synapsin 1 in the spinal neurons.
      The number of varicosities per neuron also showed a significant increase after
      neurotrophin treatment. The effects of the neurotrophins appear to be mediated by
      the Trk family of receptor tyrosine kinases, primarily through a presynaptic
      mechanism. These results suggest that BDNF and NT-3 promote functional maturation
      of synapses.

PMID- 7623112
TI  - Muscle atonia is triggered by cholinergic stimulation of the basal forebrain:
      implication for the pathophysiology of canine narcolepsy.
AB  - Narcolepsy is a sleep disorder characterized by excessive daytime sleepiness and
      rapid eye movement (REM) sleep-related symptoms, such as cataplexy. The exact
      pathophysiology underlying the disease is unknown but may involve central
      cholinergic systems. It is known that the brainstem cholinergic system is
      activated during REM sleep. Furthermore, REM sleep and REM sleep atonia similar
      to cataplexy can be triggered in normal and narcoleptic dogs by stimulating
      cholinergic receptors within the pontine brainstem. The pontine cholinergic
      system is, therefore, likely to play a role in triggering cataplexy and other REM
      related abnormalities seen in narcolepsy. The other cholinergic system that could
      be involved in the pathophysiology of narcolepsy is located in the basal
      forebrain (BF). This system sends projections to the entire cerebral cortex.
      Since acetylcholine release in the cortex is increased both during REM and wake,
      the basocortical cholinergic system is believed to be involved in cortical
      desynchrony. In the current study, we analyzed the effect of cholinergic
      compounds injected into the forebrain structures of narcoleptic and control dogs.
      We found that carbachol (a cholinergic agonist) injected into the BF triggers
      cataplexy in narcoleptic dogs while it increases wakefulness in control dogs.
      Much higher doses of carbachol bilaterally injected in the BF were, however,
      shown to trigger muscle atonia even in control dogs. These results suggest that a
      cholinoceptive site in the BF is critically implicated in triggering muscle
      atonia and cataplexy. Together with similar results previously obtained in the
      pontine brainstem, it appears that a widespread hypersensitivity to cholinergic
      stimulation may be central to the pathophysiology of canine narcolepsy.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7623113
TI  - Neuromuscular metamorphosis in the moth Manduca sexta: hormonal regulation of
      synapses loss and remodeling.
AB  - The motor system of the moth Manduca sexta is completely remodeled during the
      pupal-adult transformation (PAT). It is stable until the formation of the pupal
      stage (0% PAT), but larval motor end plates become disrupted by 5% PAT and are
      lost by 10% PAT, at the time that the muscle has begun to degenerate. Most of the
      axonal arbor is retracted by 15% with the first signs of adult sprouts appearing
      by 20% PAT, coinciding with proliferative activity in the remains of the larval
      muscle. Extensive growth of the axonal arbor begins after 30% PAT, with an
      initial phase of rapid longitudinal growth (35-50% PAT) and then the production
      of short transverse branches that then form sprays of end plates (50-70% PAT).
      Growth and maturation of the end plates occupies the remainder of metamorphosis.
      Neuromuscular metamorphosis was interfered with by systemic or local treatment
      with a mimic of the insect juvenile hormone. The results of these treatments
      suggest that some aspects of the removal of larval axonal branches requires cues
      from the target. For the sprouting response, the rapid longitudinal growth over
      the muscle appears to be due to ecdysteroids acting directly on the cell body of
      the motoneuron. By contrast, the subsequent production and maintenance of
      transverse sprouts and the corresponding end plates may be an indirect response
      to stimulation of muscle growth and differentiation by ecdysteroids.

PMID- 7623114
TI  - Olfactory marker protein mRNA is found in axons of olfactory receptor neurons.
AB  - The separation between the cell bodies of olfactory receptor neurons in the nasal
      cavity and their axon terminals in the olfactory bulb make them attractive for
      studying axonal transport. Although high molecular weight RNAs are generally
      believed to be excluded from axons of mature neurons, we demonstrate here that
      mRNA for olfactory marker protein (OMP), an abundant cytoplasmic protein
      selectively expressed in mature receptor cells, is present in rodent olfactory
      receptor axons. OMP RNA was detected by in situ hybridization at the light
      microscope level in axons and in terminals. By nuclease protection, the level of
      OMP RNA in the olfactory bulb was 5-10% of that in the olfactory epithelium where
      the cell bodies reside. In contrast to axonally transported vasopressin and
      oxytocin mRNAs, which are deficient in their 3' polyA tails, axonal OMP RNA
      fractionated as polyA+. OMP RNA was lost from axons and terminals after
      deafferentation, suggesting that OMP RNA was synthesized in receptor cell bodies
      in the epithelium and was transported into axons and terminals in the olfactory
      bulb. RNA for G(olf), a G-protein highly expressed in dendrites of mature
      olfactory receptor neurons, was not detected in the olfactory bulb. We
      hypothesize that the immature nature of the cytoskeleton and, specifically, the
      lack of tightly bundled microtubules allows transport of particular mRNAs in
      olfactory receptor axons.

PMID- 7623115
TI  - The mouse mutation reeler causes increased adhesion within a subpopulation of
      early postmitotic cortical neurons.
AB  - Early postmitotic cortical neurons are mostly corticofugal projection neurons
      that take up positions in deep cortical laminae. Later postmitotic neurons are
      preferentially localized to superficial cortical laminae. In reeler mutant mice
      it appears that cortical laminar positions with respect to birthdate are reversed
      (Caviness, 1982). In a reanalysis of reeler lamination we found that early
      postmitotic cortical neurons labeled by embryonic day (E) 11-13 injections of a
      birthdate marker, or by early postnatal day (PND) 2 retrograde labeling through
      their output projections, appear to take up positions both in the superficial and
      deep cortex. Neurons born on E11 and E12 are more likely to be situated
      superficially in the reeler cortex and neurons born on E13 are more likely to be
      situated in the deep reeler cortex. Many corticofugal projection neurons in the
      deep (but not superficial) reeler cortex either die or retract their axons before
      PND 21. We hypothesize that the earliest postmitotic (E11-E12) of the early
      postmitotic reeler cortical neurons are overly adhesive and act as a barrier to
      later postmitotic migrating neurons. In vitro cortical aggregation cultures
      confirmed that early postmitotic (E12) reeler neurons are more adhesive than
      early postmitotic (E12) wild-type neurons or late postmitotic (E16) reeler or
      wild-type cortical neurons. We suggest that the moderate wild-type preferential
      adhesion of early postmitotic cortical neurons to each other helps deep and
      superficially fated lineages to form cortical laminae.

PMID- 7623116
TI  - The orbital and medial prefrontal circuit through the primate basal ganglia.
AB  - The ventral striatum is considered an interface between limbic and motor systems.
      We followed the orbital and medial prefrontal circuit through the monkey basal
      ganglia by analyzing the projection from this cortical area to the ventral
      striatum and the representation of orbitofrontal cortex via the striatum, in the
      globus pallidus and substantia nigra. Following injections of Lucifer yellow and
      horse radish peroxidase into the medial ventral striatum, there is a very densely
      labeled distribution of cells in areas 13a and 13b, primarily in layers V and VI,
      and in medial prefrontal areas 32 and 25. Injections into the shell of the
      nucleus accumbens labeled primarily areas 25 and 32. The reaction product in the
      globus pallidus and the substantia nigra supports previous studies demonstrating
      that efferent projections from the ventral striatum are represented
      topographically in the ventral pallidum and nontopographically in the substantia
      nigra, pars compacta. Tritiated amino acid or PHA-L tracer injections into
      orbitofrontal cortex produce dense patches of terminal labeling along the medial
      edge of the caudate nucleus and the dorsal part of the nucleus accumbens. These
      results demonstrate that the orbital prefrontal cortex projects primarily to the
      medial edge of the ventral striatum and to the core of the nucleus accumbens. The
      arrangement of terminals in the globus pallidus and substantia nigra show two
      different patterns. Thus, the orbital and medial prefrontal cortex is represented
      in a confined region of the globus pallidus but throughout an extensive area of
      the dorsal substantia nigra. Terminals are extensive throughout the region of the
      dopaminergic neurons, suggesting that this input may influence a wide area of
      both the striatum and frontal cortex.

PMID- 7623117
TI  - Differential properties of cells in the feline primary visual cortex providing
      the corticofugal feedback to the lateral geniculate nucleus and visual claustrum.
AB  - We have examined the responses of 141 layer VI cells in the feline visual cortex.
      Within this group we compared the responses of a subpopulation of cells checked
      for connectivity by electrical stimulation in the dLGN and the visual claustrum.
      The antidromically identified corticogeniculate projecting cells had relatively
      short receptive fields, as judged from length response curves, measured
      quantitatively, and were located at the "short" end of the receptive field length
      spectrum seen in the general population. Of the 17 corticogeniculate projecting
      cells, 71% were S type cells, which were typically monocular and directionally
      selective, with relatively long latencies following electrical stimulation. The
      remaining 29% were C type cells, also directionally selective, but with a wider
      spread of ocular dominance preferences and shorter latencies following electrical
      stimulation. S and C type subpopulations did not differ in their receptive field
      lengths. The mean receptive field length for this subpopulation was 2.2 degrees
      +/- 0.27, the shortest field being 1 degrees and the longest 5 degrees. The five
      layer VI cells activated by electrical stimulation from electrodes within the
      dorsocaudal (visual) claustrum all had much longer receptive field lengths than
      the corticogeniculate population, often 10 degrees or longer and were monocular
      and directionally selective S type cells. These data indicate that the
      information carried in the corticogeniculate stream (and that from layer VI
      directly to layer IV carried by axon collaterals) is relatively tightly focused
      in spatial terms whilst the less spatially focused, long receptive field output
      from layer VI projects to the claustrum.

PMID- 7623118
TI  - Comparison of ionic currents expressed in immature and mature muscle cells of an
      ascidian larva.
AB  - We have compared the voltage-gated ion channels present in larval ascidian muscle
      at two developmental stages: muscle precursor cells just after the terminal cell
      division and mature contractile muscle, 7-11 hr later. All precursor cells
      express a high-threshold transient Ca current and a slowly activating delayed K
      current, and about half the cells express a low-threshold transient Ca current.
      An inwardly rectifying K current, which had been present from fertilization until
      just before the terminal cell division, is absent. Mature muscle retains two of
      the tailbud currents: the low-threshold transient Ca current and the slow delayed
      K current, although at larger densities, and also expresses a high-threshold Ca
      current that is similar in most respects to the precursor cell current but that
      lacks inactivation. In addition, mature muscle expresses two rapidly activating
      outward K currents, one voltage and one Ca dependent, that generate a composite
      outward K current that is eight times larger and activates eight times faster
      than the tailbud K current. Mature muscle also reexpresses the inward rectifier.
      We propose that the transient absence of the inward rectifier and the slow
      activation of the delayed K current early in development create a window of
      developmental time when spontaneous electrical activity is likely.

PMID- 7623119
TI  - Characterization of the human 5-HT2A receptor gene promoter.
AB  - The regulation of 5-HT2A receptor (5-HT2AR) expression has been implicated in a
      variety of pathological processes and has been shown to be extremely complicated
      and controversial. In order to understand the mechanisms of regulation of this
      receptor, it is important to characterize its promoter. In this report, the 5'
      end of the human 5-HT2AR gene was cloned and characterized. Anchored PCR mapped
      multiple transcription initiation sites at nucleotides -1157, -1137, -1127, and 
      496. Transfection of chimeric growth hormone plasmids containing various DNA
      fragments into 5-HT2AR-positive human cell lines (SHSY-5Y, neuroblastoma; HeLa,
      cervix carcinoma) showed that the 0.74 kb HaeIII/PvuII fragment, which
      encompasses the initiation sites between -1157 and -1127 and 5' of the downstream
      initiation site (at -496), exhibited significant promoter activity. This promoter
      activity was not affected by the sequence upstream of the 0.74 kb fragment. The
      sequence downstream (the 0.45 kb PvuII/SmaI fragment) strongly repressed this
      promoter activity, suggesting the presence of a silencer. Sequence analysis
      combined with gel retardation and Dnase 1 footprinting assay identified multiple
      cis and trans elements for this fragment, including Sp1, PEA3, cyclic AMP
      response element (CRE)-like sequence, and E-boxes. Two novel transcription
      factors have been detected by gel retardation and DNase 1 footprinting assay; one
      of them may be specific for human. The transcription factors and promoter
      activities were low in the negative cell line NCI-H460 (human lung large cell
      carcinoma). Interestingly, the 0.39 kb fragment, isolated from the 3' end of the
      0.74 kb fragment, exhibited the highest promoter activity. The possibility that
      this 0.39 kb fragment may be an alternative promoter is discussed. These new data
      are essential for further study of the regulation of 5-HT2AR gene expression.

PMID- 7623120
TI  - Chronic elevation of secreted amyloid precursor protein in subcortically lesioned
      rats, and its exacerbation in aged rats.
AB  - Subcortically lesioned rats were used as an animal model of some of the
      neurochemical and behavioral deficits of Alzheimer's disease (AD) to investigate
      the in vivo expression and metabolism of amyloid precursor protein (APP).
      Previously, the rapid and persistent induction of APP was described in cerebral
      cortices after disruption of its cholinergic, serotonergic, or noradrenergic
      afferents. In the present study, this induction was found to lead to the elevated
      secretion of APP into the cerebrospinal fluid of lesioned animals. Lesions of the
      forebrain cholinergic system in aged rats caused an even greater increase in the
      CSF levels of secreted APP. Antibodies to the extracellular domain of APP
      detected the protein whereas antibodies to the cytoplasmic region did not,
      indicating that the APP present in CSF was of the soluble form.
      Immunoprecipitation with an A beta sequence-specific antibody followed by
      immunoblot analysis indicated that a significant portion of secreted APP was of
      the species that contains at least the first 28 amino acids of the A beta
      sequence (APP gamma or APPA beta). By contrast, very low levels of A beta peptide
      were detected in CSF. The secretion was accompanied by an elevation of cellular C
      terminal fragments of the APP in the lesioned cortex. Consistent with our
      previous results, this increased APP secretion was caused by lesions of
      subcortical cholinergic and serotonergic systems. The postlesion time course of
      APP secretion showed an initial reduction of APP (1 hr postlesion) in CSF
      followed by an eventual twofold elevation 1-6 weeks later. These results indicate
      that the induction of APP in response to loss of subcortical innervation leads to
      elevated secretion of a soluble form of cortically derived APP that contains
      significant portions of the A beta sequence.

PMID- 7623121
TI  - Cellular localization of synaptotagmin I, II, and III mRNAs in the central
      nervous system and pituitary and adrenal glands of the rat.
AB  - Three isoforms of synaptotagmin, a synaptic vesicle protein involved in
      neurotransmitter release, have been characterized in the rat, although functional
      differences between these isoforms have not been reported. In situ hybridization
      was used to define the localization of synaptotagmin I, II, and III transcripts
      in the rat CNS and pituitary and adrenal glands. Each of the three synaptotagmin
      genes has a unique expression pattern. The synaptotagmin III gene is expressed in
      most neurons, but transcripts are much less abundant than the products of the
      synaptotagmin I and II genes. A majority of neurons in the forebrain expressed
      both synaptotagmin I and III mRNAs while synaptotagmin II gene expression was
      confined to subsets of neurons in layers IV-VI of the cerebral cortex, in the
      dentate granule cell region, the hilus, and the CA1-CA3 areas of the hippocampus.
      In the cerebellum, all three transcripts were visualized in the granule cell
      layer. Furthermore, synaptotagmin I probes revealed striking differences between
      distinct populations of neurons, as in addition to moderate labeling of granule
      cells, much more prominent hybridization signals were detected on scattered cell
      bodies likely to be Golgi interneurons. In the most caudal part of the brain,
      synaptotagmin II transcripts were abundant and were coexpressed with
      synaptotagmin III mRNAs. This pattern was found in putative motoneurons of the
      spinal cord, suggesting that the two isoforms might be involved in exocytosis at
      the neuromuscular junction. Only synaptotagmin I mRNAs were detected in the
      anterior and intermediate pituitary and in adrenal medullary cells. These data
      reveal an unexpectedly subtle segregation of the expression of synaptotagmin
      genes and the existence of multiple combinations of synaptotagmin isoforms which
      may provide diversity in the regulation of neurosecretion.

PMID- 7623122
TI  - Nerve growth factor (NGF) differentially regulates the chemosensitivity of adult
      rat cultured sensory neurons.
AB  - We have studied the effects of NGF on the chemosensitivity of adult rat DRG
      neurons over a 1-2 week period in vitro, using voltage-clamp and radioactive ion
      flux methods. A sustained proton evoked current was reversibly lost in NGF-free
      medium after 1 week. Proton-evoked efflux of radioactive 86Rb+ ions was also
      depressed in NGF deprived cultures, although depolarization with 40 mM potassium
      still evoked a large 86Rb+ efflux. A similar reversible loss of capsaicin
      sensitivity was noted. The response to GABA and a second, transient proton evoked
      current were also regulated by NGF, but over a longer time course. In contrast,
      the sensitivity to ATP was not influenced by the presence or absence of NGF.
      These data show that NGF regulates some, but not all, chemosensitivities of DRG
      neurons and that loss of sensitivity occurs at different rates for different
      agonists. The precise co-regulation of the response to capsaicin and the
      sustained response to protons provides further evidence that protons activate
      capsaicin-operated ion channels.

PMID- 7623123
TI  - Developmental analysis of murine Promyelocyte Leukemia Zinc Finger (PLZF) gene
      expression: implications for the neuromeric model of the forebrain organization.
AB  - Promyelocyte Leukemia Zinc Finger (PLZF) is a Kruppel-like zinc finger gene
      previously identified in a unique case of acute promyelocytic leukemia (APL) as
      the counterpart of a reciprocal chromosomal translocation involving the retinoic
      acid receptor alpha gene (RAR alpha). PLZF is highly conserved throughout
      evolution from yeast to mammals. To elucidate its role, we isolated the murine
      PLZF gene and studied its expression during embryogenesis. PLZF is expressed in
      an extremely dynamic pattern with transcripts appearing at E 7.5 in the anterior
      neuroepithelium and quickly spreading to the entire neuroectoderm until E 10. At
      E 8.5, PLZF is transcribed in most of the endoderm. During mid to late gestation
      PLZF is expressed in restricted domains of the developing CNS as well as in
      specific organs and body structures. We have focused our attention on the
      developing forebrain where PLZF is transcribed in a transverse, segment-like
      domain corresponding to the anterior pretectum, in the alarmost part of the
      dorsal thalamus, in the epithalamus, and in the hypothalamus along a defined
      longitudinal subdomain. Furthermore, PLZF is expressed in several segmentary
      boundaries, among them, the zona limitans intrathalamica. Combined analysis with
      other regionally restricted genes, such as Orthopedia and Dlx1, indicates that in
      the hypothalamus the PLZF domain is contained within that of Orthopedia and both
      are complementary to that of Dlx1. Our data suggest a role for PLZF in the
      establishment and maintenance of transverse identities, longitudinal subdomains,
      and interneuromeric boundaries, providing additional evidences in favor of the
      neuromeric organization of the forebrain.

PMID- 7623124
TI  - Localization and organization of the central pattern generator for hindlimb
      locomotion in newborn rat.
AB  - An in vitro preparation of newborn rat isolated brainstem/spinal cord was used in
      order to locate the spinal network responsible in mammals for producing patterned
      locomotor activity. The spinal cord was partitioned by building Vaseline walls at
      various lumbar levels. When a mixture of serotonin and N-methyl-D,L-aspartate was
      bath applied to the upper lumbar cord (L1/L2 segments), rhythmic locomotor-like
      activity was induced and recorded in all the lumbar segments (from L1 to L5).
      Conversely, when the mixture of transmitters was bath applied to the lower lumbar
      cord, only tonic activity was induced in the lower lumbar segments. Intracellular
      recordings performed on motoneurons revealed that during elicited L1/L2 locomotor
      like activity, they received a rhythmic synaptic drive that was often below the
      threshold for spiking, because the excitability of the neurons was too low. When
      the L1/L2 segments were isolated, their burst production capacities remained. The
      network located at the L1/L2 level was found to be responsible not only for
      generating the rhythm but also for organizing its alternating pattern. We
      demonstrated that the rhythmic synaptic drive that the motoneurons receive during
      locomotor-like activity comes directly from the L1/L2 network and that there is
      no relay at the segmental level. We conclude from our study that the network that
      organizes locomotion in the newborn rat is not segmentally distributed but is
      restricted to a specific part of the cord. This finding has important
      consequences, since it means that it is now feasible to study the activity of the
      rhythmic spinal network independently from that of the motoneurons.

PMID- 7623125
TI  - Neuronal activity in the primate hippocampal formation during a conditional
      association task based on the subject's location.
AB  - The hippocampal formation (HF) functions in two domains of memory: spatial and
      nonspatial associative memory. The HF includes the hippocampus proper, the
      dentate gyrus, and the subicular complex. Studies of spatial correlates of HF
      neuronal activity have revealed that a subject's location in space can impose
      critical constraints on patterns of neuronal activity in the HF. This report
      compares monkey HF neuronal responses in two kinds of stimulus-response
      association tasks (go/no-go tasks with symmetrical reinforcement). In a place
      dependent, conditional, stimulus-response association (PCA) task, the subject's
      location was the condition upon which stimulus (object)-behavioral response
      association depended. In a place-in-dependent, simple, stimulus-response
      association (ISA) task, the object-behavioral response contingency was
      independent of the subject's location. Of 329 neurons recorded, the activity of
      88 increased or decreased significantly in response to the presentation of an
      object during the PCA task. Responses of 17 neurons depended differentially on
      specific combinations of object, place, and behavior in the PCA task (specific
      combination neurons). These specific-combination responses do not simply reflect
      object-behavioral response association in the PCA task, since neuronal responses
      in the same object-behavioral response association were not restored in the ISA
      task in which there was no dependence on the subject's location. This suggests
      the influence of location on HF neuronal responses in object-behavioral response
      association when the subject's location is imposed as a condition. Responses of
      12 neurons differentiated the kind of object in the PCA task (object-differential
      neurons). In the ISA task, most object-differential responses diminished or
      disappeared. Since the HF object-differential responses elicited by the
      conditions imposed by the PCA task. Characteristics of the two neuron types
      suggest that HF neurons encode both stimulus percept and attributes such as the
      place where the stimulus is presented and the conditional relation imposed in the
      task.

PMID- 7623127
TI  - Three phases of TRH-induced facilitation of exocytosis by single lactotrophs.
AB  - Membrane capacitance measurements were used to study neuropeptide modulation of
      exocytosis by perforated patch clamped rat lactotrophs. We report that
      depolarizing voltage-clamp pulses evoke exocytosis that is steeply dependent on
      Ca2+ influx through voltage-gated Ca2+ channels. Furthermore, we find that the
      neuropeptide TRH (thyrotropin-releasing hormone) acts in three phases to promote
      exocytosis. First, TRH transiently (within approximately 0.5 min) triggers
      depolarization- and extracellular Ca(2+)-independent exocytosis. Second, within 3
      min of application, TRH facilitates depolarization-evoked exocytosis while
      inhibiting voltage-gated Ca2+ current. Finally, after 8 min, TRH further enhances
      depolarization-evoked exocytosis by increasing high-voltage-activated (HVA) Ca2+
      channel current. Activation of protein kinase C (PKC) with a phorbol ester also
      stimulates depolarization-evoked exocytosis by increasing Ca2+ current.
      Therefore, PKC can only account for the last effect of TRH. Thus, a single
      neuromodulator may employ several temporally distinct mechanisms to stimulate
      peptide secretion.

PMID- 7623126
TI  - Axonal growth and fasciculation linked to differential expression of BDNF and NT3
      receptors in developing cerebellar granule cells.
AB  - In the developing cerebellum, young granule neurons in the external germinal
      layer respond preferentially to BDNF, while mature neurons within the inner
      portion of the cerebellum respond preferentially to NT3. Here we show that this
      anatomic distinction reflects a developmentally regulated switch at the level of
      neurotrophin receptor gene expression. The salient feature of the developmental
      switch is a change in the ration of mRNA transcripts encoding functional BDNF and
      NT3 receptor tyrosine kinases. The ratio of the BDNF receptor trkB to the NT3
      receptor trkC reverses from 5:1 in neonatal cerebellum to 1:3 in adult
      cerebellum. TrkB and TrkC are closely related transmembrane tyrosine protein
      kinases. However, activation of BDNF and NT3 receptors in cerebellar granule
      neurons do not give equivalent biological responses. In aggregate cell culture
      and single cell assays, BDNF enhances axonal outgrowth of early granule cells by
      influencing neurite elongation. In contrast, NT3 alters the morphology of
      outgrowth. Collectively, these findings suggest that regulation of neurotrophin
      receptors during cerebellar development is important for the timing and
      morphology of axonal growth.

PMID- 7623128
TI  - Expression, secretion, and age-related downregulation of pigment epithelium
      derived factor, a serpin with neurotrophic activity.
AB  - Retinal pigment epithelial (RPE) cells form a functional complex with
      photoreceptor neurons of the retina, interacting through the interphotoreceptor
      matrix (IPM). We now provide evidence that the gene for pigment epithelium
      derived factor (PEDF), a protein possessing neurotrophic and neuronal-survival
      activities, is highly expressed by both fetal and young adult RPE cells. PEDF
      mRNA is present in RPE cells of the human eye at 17 weeks of gestation,
      demonstrating its potential for action in vivo during early retinal development.
      The PEDF protein is secreted in vivo where it constitutes a part of the fetal and
      adult IPM surrounding photoreceptor outer segments. A polyclonal PEDF antibody
      recognizes at least four isoforms of secreted human and bovine PEDF by two
      dimensional gel analysis, and detects a similar 50 kDa protein in the IPM of
      several other vertebrate species. Within soluble extracts of RPE cells, however,
      where little, if any, of the 50 kDa species can be detected, an immunoreactive 36
      kDa protein is observed by Western blot analysis. By immunofluorescence, PEDF is
      localized intracellularly in association with the nucleus, presumptive secretory
      granules, and cytoskeletal elements of cultured RPE cells with PEDF and actin
      antibodies colocalizing to the same cytoskeletal structures. During initial
      stages of attachment, PEDF and actin also concentrate at the tips of pseudopods
      extended by the cultured RPE cells. However, with successive passages, synthesis,
      and secretion of the PEDF protein as well as transcription of its mRNA decrease
      and are lost by about 10 passages. In parallel, cultured RPE cells lose their
      proliferative potential and change from an epithelial-like morphology in early
      passages to a more fibroblast-like appearance by about the 10th passage. PEDF is
      thus apparently present intracellularly and extracellularly in both fetal and
      early adult periods where it could be involved in cellular differentiation and
      survival and with its loss, in the onset of senescence.

PMID- 7623129
TI  - The Shaker-like potassium channels of the mouse rod bipolar cell and their
      contributions to the membrane current.
AB  - RT PCR on mRNA from enzymatically dissociated, isolated bipolar cells showed that
      these neurons express the Shaker-like K+ channels Kv1.1, Kv1.2, and Kv1.3.
      Immunohistochemical localization showed each channel to have a unique subcellular
      distribution: Kv1.1 immunoreactivity was detected in the dendrites and axons
      terminal, whereas Kv1.2 and Kv1.3 subunits were localized to the axon and the
      postsynaptic membrane of the rod ribbon synapse, respectively. Whole-cell patch
      clamp recordings indicated that the activation voltage of the delayed rectifier
      current of the isolated bipolar cell and the inhibitory constants for current
      blockade by TEA, 4-AP, and Ba2+ were similar to these same properties measured
      for Kv1.1 expressed in oocytes. However, the TEA and 4-AP inhibitory constants
      for the bipolar cell current differed from the inhibitory constants for Kv1.2 or
      Kv1.3. These results suggest that the current of the isolated rod bipolar cell is
      most similar to Kv1.1 but that all three channels may function in the intact
      retina to allow complex modulation of retinal synaptic signals.

PMID- 7623130
TI  - Persistence of early-generated neurons in the rodent subplate: assessment of cell
      death in neocortex during the early postnatal period.
AB  - In the rat, the deepest neocortical layer forms a conspicuous cell band known as
      layer Vlb. Cells in layer Vlb are among the first to differentiate, and it has
      been regarded as an homolog to the subplate of primates and carnivores. Cell
      death has been considered a universal feature of subplate cells. In order to
      assess the validity of this assertion, we examined the sequence of generation and
      the extent of cell death in layer Vlb. This was achieved using injections of 3H
      thymidine and two methods for the direct visualization of apoptotic figures.
      Single injections of 3H-thymidine were performed between E12 and E15 (E0 is the
      day of insemination), and brains were examined at different postnatal ages
      between P1 and P63. The number of heavily labeled cells were counted in layer Vlb
      in six standard, equally spaced coronal sections in each brain. Single injections
      at E12 labels about 3% of the entire population of layer Vlb cells, 17% at E13,
      30% at E14, and < 1% at E15. Our results indicate that the absolute number of
      heavily labeled cells in layer Vlb remains constant. The analysis of variance
      (one-way ANOVA) showed that the difference among the group means was not
      significant from P1 to P63 after injections at either E12, E13, or E14. In order
      to confirm these results, we evaluated the distribution of pyknotic (apoptotic)
      cell bodies in the neocortex. Apoptotic cells were visualized in Nissl
      preparations and by histochemical staining using an in situ apoptosis detection
      kit. The analysis was performed in rats from E18 to P15. Both methods gave
      comparable results. We found that the amount of cell death in layer Vlb is
      neither particularly prominent nor significantly different from that which occurs
      in the remaining neocortical layers, apart from layer II and in the white matter
      of the corpus callosum. We conclude that neuronal death does not play any
      significant role in the rodent subplate.

PMID- 7623131
TI  - A presynaptic mechanism accounts for the differential block of nicotinic synapses
      on sympathetic B and C neurons by d-tubocurarine.
AB  - The effects of d-tubocurarine (dTC) on nicotinic synapses on sympathetic B and C
      neurons in the bullfrog were compared by recording trains of postganglionic
      compound action potentials (CAPs) at 0.5-20 Hz. Block by dTC was strongly use
      dependent in that the IC50 shifted almost 10-fold with increasing stimulus
      frequency. Maximum sensitivity to dTC occurred at 5 Hz in the B system and at 20
      Hz in the C system. Recovery during posttrain periods was characterized by
      transient reduction of CAP amplitude in the B system and by transient enhancement
      of CAP amplitude in the C system. Thus, dTC distinguished between nicotinic
      synapses on the two cell types. The cell-specific effects of dTC could arise from
      differences in postsynaptic or presynaptic nicotinic receptors, or from
      differences in acetylcholine (ACh) release. We tested these possibilities using
      intracellular recording. Based on comparison with iontophoretic responses to ACh,
      changes in EPSP amplitude during repetitive stimulation in dTC could not be
      explained by altered postsynaptic sensitivity. The block of nicotinic receptors
      was further analyzed by recording synaptic currents. In B and C cells, 3 microM
      dTC competitively antagonized EPSC amplitude by 54% without any sign of open
      channel block. In B cells, comparison of trains in normal Ringer and dTC revealed
      a constant fractional reduction in EPSC amplitude, thereby indicating that
      presynaptic nicotinic receptors do not influence release. In the C system, dTC
      had no effect on peptidergic EPSPs, thereby suggesting that presynaptic nicotinic
      receptors also do not influence peptide release. We conclude that the
      differential effects of dTC on nicotinic transmission are indirect consequences
      of differences in ACh release by preganglionic B and C neurons.

PMID- 7623132
TI  - In vitro classical conditioning of abducens nerve discharge in turtles.
AB  - In vitro classical conditioning of abducens nerve activity was performed using an
      isolated turtle brainstem-cerebellum preparation by direct stimulation of the
      cranial nerves. Using a delayed training procedure, the in vitro preparation was
      presented with paired stimuli consisting of a 1 sec train stimulus applied to the
      auditory nerve (CS), which immediately preceded a single shock US applied to the
      trigeminal nerve. Conditioned and unconditioned responses were recorded in the
      ipsilateral abducens nerve. Acquisition exhibited a positive slope of conditioned
      responding in 60% of the preparations. Application of unpaired stimuli consisting
      of CS-alone, alternate CS and US, or backward conditioning failed to result in
      conditioning, or resulted in extinction of CRs. Latencies of CR onset were timed
      such that they occurred midway through the CS. Activity-dependent uptake of the
      dye sulforhodamine was used to examine the spatial distribution of neurons
      labeled during conditioning. These data showed label in the cerebellum and red
      nucleus during conditioning whereas these regions failed to label during
      unconditioned responses. Furthermore, the principal abducens nucleus labeled
      heavily during conditioning. These findings suggest the feasibility of examining
      classical conditioning in a vertebrate in vitro brainstem-cerebellum preparation.
      It is postulated that the abducens nerve CR represents a behavioral correlate of
      a blink-related eye movement. Multiple sites of conditioning are hypothesized,
      including the cerebellorubral circuitry and brainstem pathways that activate the
      principal abducens nucleus.

PMID- 7623133
TI  - Central endogenous opioid inhibition of supraoptic oxytocin neurons in pregnant
      rats.
AB  - Naloxone increases oxytocin secretion in pregnant rats, suggesting restraint by
      endogenous opioids but we have previously reported that oxytocin nerve terminals
      in the neural lobe become desensitized to opioid actions in late pregnancy.
      Therefore, we sought evidence for opioid inhibition on oxytocin cell bodies and
      their inputs at this time. In conscious 21 d pregnant rats naloxone increased the
      number of neurons expressing Fos (an indicator of neuronal activity) in the
      supraoptic nucleus (SON) but had no effect on 16 d pregnant or virgin rats.
      Release of oxytocin within the SON, measured by microdialysis in conscious rats,
      was also increased by naloxone in late pregnancy but not before. Nor
      binaltorphimine, a specific kappa- opioid antagonist, did not increase Fos or
      affect oxytocin release within the SON in any group. In anesthetized rats the
      firing rate of SON neurons was recorded and oxytocin neurons identified by an
      excitatory response to intravenous cholecystokinin. Naloxone potentiated the
      cholecystokinin-induced firing rate response on day 21 of pregnancy but not in 16
      d pregnant or virgin rats. Blood sampling in anesthetized rats showed that
      naloxone also increased the oxytocin secretory response to cholecystokinin in
      late pregnant rats. We conclude that in late pregnancy, after day 16, endogenous
      opioids inhibit oxytocin neurons either directly, on their cell bodies, or
      presynaptically on inputs. These endogenous opioids do not act through kappa-
      opioid receptors since nor-binaltorphimine was ineffective, but may act via mu
      opioid receptors. Thus, the opioids restrain premature oxytocin secretion until
      parturition when there is a high demand for it.

PMID- 7623134
TI  - Oxytocin receptor mRNA expression in the ventromedial hypothalamus during the
      estrous cycle.
AB  - Changes in OR mRNA expression in the ventromedial hypothalamus (VMH) in relation
      to the estrous cycle were measured by in situ hybridization with a rat oxytocin
      receptor (OR) probe. Binding studies have localized ORs to various brain regions,
      and have detected a high density of receptors in the VMH, a nucleus containing
      large numbers of estrogen responsive neurons. Previous studies in this lab have
      reported a significant increase in OR mRNA expression in the VMH in
      ovariectomized rats treated with estrogen. The present study was designed to
      determine whether changes in steroid hormone levels across the estrous cycle
      result in induction of OR mRNA expression. Autoradiographic studies revealed
      differences in OR mRNA expression in the rostral and caudal as well as medial and
      lateral aspects of the VMH. OR mRNA levels were highest in the caudal portion of
      the vIVMH on the afternoon (16:00 hr) of proestrus. The rostral region exhibited
      a high level of expression in the ventrolateral region of the VMH on the morning
      (9:00 hr) of proestrus and in the dorsomedial region of the VMH on the afternoon
      of proestrus. Little or no OR mRNA expression was evident in the rostral or
      caudal VMH on the morning or evening of diestrus. These results support previous
      findings which showed a regulation of OR binding by gonadal steroids and suggest
      that this may be due to altered expression of the OR gene. These effects suggest
      a possible role of ORs in the oxytocin stimulated release of luteinizing hormone.

PMID- 7623135
TI  - GABA neurotransmission in the hypothalamus: developmental reversal from Ca2+
      elevating to depressing.
AB  - GABA is the primary inhibitory transmitter of the adult hypothalamus, synthesized
      by many neurons and found in 50% of the presynaptic boutons. GABA causes a
      decrease in Ca2+ in mature hypothalamic neurons in vitro by depressing cellular
      activity through opening Cl- channels. Despite the early expression of GABAA
      receptors in the embryonic hypothalamus (E15), the cellular function of GABA in
      the developing hypothalamus has received little attention. In the present study
      the role of GABA in modulating intracellular Ca2+ in developing hypothalamic
      neurons was studied with fura-2 digital imaging. GABA (0.5-500 microM) applied to
      embryonic hypothalamic neurons elicited a dramatic and rapid increase in
      intracellular Ca2+ This Ca2+ rise could be completely blocked by the GABAA
      antagonist bicuculline (20 microM) and persisted in the presence of tetrodotoxin
      (1 microM). The Ca2+ elevation induced by GABA was greater than that of equimolar
      concentrations of the excitatory transmitter glutamate in early development. The
      number of E15 neurons that responded to GABA with a Ca2+ rise increased during
      the first few days of culture, reaching 78% after 4 d in vitro. The Ca2+ rise was
      87% blocked by cadmium (100 microM) and 85% blocked by nimodipine (1 microM),
      indicating that the mechanism of Ca2+ increase was primarily via L-type voltage
      operated Ca2+ channels. Addition of bicuculline to synaptically coupled cultures
      caused a significant decrease in Ca2+ 4-10 d after culturing, indicating
      hypothalamic neurons were secreting GABA at an early age of development, and that
      sufficient GABA was released to elicit an increase in Ca2+. This effect was seen
      even after blocking all glutamatergic activity with glutamate receptor
      antagonists. In contrast, GABA elicited no Ca2+ rise in older neurons (> 18 d in
      vitro), and the action of bicuculline reversed and caused a large increase in
      Ca2+ in spontaneously active neurons. Similar findings were obtained in cultures
      enriched in GABAergic neurons from the suprachiasmatic nucleus. To determine if
      the Ca2+ stimulating role of GABA on developing neurons was restricted to the
      hypothalamus and a few other regions, or whether it might exist throughout the
      brain, we examined the Ca2+ responses in cultured olfactory bulb, cortex,
      medulla, striatum, thalamus, hippocampus, and colliculus. The majority (75%) of
      developing neurons from each region showed a Ca2+ rise in response to GABA.
      Together these data suggest that GABA elevates Ca2+ in developing, but not
      mature, neurons from the hypothalamus and all other brain regions
      examined.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7623136
TI  - Neurotrophin-4/5 enhances survival of cultured spiral ganglion neurons and
      protects them from cisplatin neurotoxicity.
AB  - Destruction of spiral ganglion neurons (SGNs) induced by injury and toxins is one
      of the major causes for hearing loss. Here we report that neurotrophin-4/5 (NT
      4/5), a member of the nerve growth factor family, promoted survival of postnatal
      rat SGNs up to threefold in dissociated cell cultures. The survival-promoting
      potency of NT-4/5 was equivalent to that of BDNF and stronger than that of NT-3.
      In contrast, NGF showed no detectable effects. Immunohistochemistry, with TrkB
      and TrkA antisera, revealed that these neurons produced TrkB protein, the
      functional receptor for NT-4/5 and BDNF, but not TrkA protein, the high-affinity
      receptor for NGF. The survival-promoting activity of NT-4/5 was completely
      inhibited by TrkB-IgG fusion protein. These results suggest that NT-4/5 is a
      specific survival factor for SGNs. In addition, NT-4/5 protected the SGNs from
      neurotoxic effects of the anti-cancer drug, cisplatin. Thus, NT-4/5 may have
      therapeutic value in preventing hearing impairment caused by damage to primary
      auditory afferent neurons.

PMID- 7623137
TI  - Expression and activity-dependent changes of a novel limbic-serine protease gene
      in the hippocampus.
AB  - A novel murine cDNA which encodes a protein designated neuropsin was cloned.
      Northern and in situ hybridization analyses demonstrated that neuropsin mRNA is
      expressed specifically in the limbic system of mouse brain and is localized at
      highest concentration in pyramidal neurons of the hippocampal CA1-3 subfields.
      Direct hippocampal stimulation and kindling induced by amygdaloid stimulation
      caused a significant bilateral change in neuropsin mRNA level in the hippocampal
      pyramidal neurons. The activity-dependent changes and the specific localization
      indicate that neuropsin is involved in hippocampal plasticity.

PMID- 7623138
TI  - An evaluation of the nitric oxide/cGMP/cGMP-dependent protein kinase cascade in
      the induction of cerebellar long-term depression in culture.
AB  - Cerebellar long-term depression (LTD) is a model system of information storage in
      which a persistent attenuation of the parallel fiber-Purkinje neuron (PN) synapse
      is induced by conjunctive stimulation of parallel fiber and climbing fiber inputs
      at low frequency. As some studies have suggested that release of the gaseous
      second messenger, nitric oxide (NO), in the molecular layer and the consequent
      activation of soluble guanylate cyclase and cGMP-dependent protein kinase (PKG)
      in the PN, is necessary for LTD induction, we have further examined this
      hypothesis using a cell culture protocol. In cerebellar cultures made from
      transgenic mice in which the gene for neuronal nitric oxide synthase (nNOS) has
      been rendered null, LTD induced by glutamate/depolarization conjunctive
      stimulation was indistinguishable from that in cultures from wild-type mice in
      terms of amplitude, rate of onset, and duration. Bath application of cGMP analogs
      produced a large (80%), transient attenuation of glutamate-gated inward currents.
      However, application of an activator of soluble guanylate cyclase or an inhibitor
      of type V cGMP-phosphodiesterase did not mimic the effect of cGMP analogs, and
      inclusion of cGMP analogs in the patch pipette did not give rise to a slowly
      developing attenuation, suggesting that these compounds exert their effects at
      the cell surface. Free Ca was measured in the distal dendritic arbor of single
      PNs by fura-2 microfluorimetry.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7623139
TI  - Pattern recognition of amino acid signatures in retinal neurons.
AB  - Pattern recognition of amino acid signals partitions the cells of the goldfish
      retina into nine statistically unique biochemical theme classes and permits a
      first-order chemical mapping of virtually all cellular space. Photoreceptors,
      bipolar cells, and ganglion cells display a set of unique, nominally
      glutamatergic type E1, E1+E2, and E4 signatures, respectively. All horizontal
      cells are assignable to a GABAergic gamma 2 class or a non-GABAergic class with a
      glutamate-rich E3 signature. The amacrine cell layer is largely a mixture of (1)
      a taurine-dominated T1 Muller's cell signature and (2) GABAergic gamma 1,
      glycinergic G1, and dual glycinergic/GABAergic G gamma 1 amacrine cell
      signatures. Several major conclusions emerge from this work. (1) Glutamatergic,
      GABAergic, and glycinergic neural signatures and glial signatures account for
      over 99% of the cellular space in the retina. (2) All known neurons in the
      goldfish retina are associated with a set of conventional nonpeptide
      neurotransmitters. (3) Multiple forms of metabolic profiles are associated with a
      single nominal neurotransmitter category. (4) Glutamate and aspartate contents
      exhibit overlapping distributions and are not adequate univariate probes for
      identifying cell classes. (5) Signatures can serve as quantitative measures of
      cell state.

PMID- 7623140
TI  - Induction of interleukin-6 in axotomized sensory neurons.
AB  - RNA from rat dorsal root ganglia was analyzed in search of potentially beneficial
      cytokines that are induced in dorsal root ganglia by nerve injury. By reverse
      transcription, the PCR, and Southern blotting, interleukin-6 mRNA was detected
      during development but not in normal adult dorsal root ganglia, reappeared within
      1 d of sciatic nerve transection, was maximally increased after 2 and 4 d, and
      decreased below the threshold of detection within 1 week. By RNase protection
      assay, interleukin-6 mRNA was consistently present in RNA from dorsal root
      ganglia removed from rats 4 d following transection but not in control dorsal
      root ganglia. Interleukin-6 bioactivity was also present in dorsal root ganglia
      following nerve injury. By in situ hybridization, interleukin-6 mRNA was
      localized within large and medium-sized axotomized neurons. In summary, some
      sensory neurons respond to axotomy with a brisk transient increase in synthesis
      of interleukin-6. Injury to the sciatic nerve also induced mRNAs for interleukin
      1 beta and tumor necrosis factor-alpha in dorsal root ganglia. The inductions of
      interleukin-1 beta and tumor necrosis factor-alpha mRNAs were later and more
      sustained than that of interleukin-6 mRNA. The cellular sources of these two
      cytokines have not been defined.

PMID- 7623141
TI  - Characterization of a forebrain gaze field in the archistriatum of the barn owl:
      microstimulation and anatomical connections.
AB  - We present evidence that the archistriatum in the forebrain of the barn owl
      participates in gaze control, that it can mediate gaze changes independently of
      the optic tectum (OT), and that it projects in parallel to both the OT and to
      saccade-generating circuitry in the brainstem tegmentum. These properties are
      similar to those of the frontal eye fields (FEF) in the prefrontal cortex of
      primates. The forebrain was surveyed for sites where electrical microstimulation
      would induce head saccades. Head (and eye) saccades were elicited from the
      anterior 70% of the archistriatum, a region that we refer to as the archistriatal
      gaze fields (AGF). At single stimulation sites in the AGF, saccade amplitude
      tended to vary as a function of stimulation parameters (current strength, pulse
      frequency, and train duration) and starting head position. In contrast, saccade
      direction was largely independent of these parameters. Saccade direction did vary
      over a wide range of primarily contraversive directions with the site of
      stimulation in the AGF. Using anatomical pathway tracing techniques, we found
      that the archistriatum projects strongly and in parallel to the deep layers of
      the OT and to nuclei in the midline brainstem tegmentum. Previous work has shown
      that electrical microstimulation of either of these brainstem regions evokes
      saccadic movements of the head and/or eyes (du Lac and Knudsen, 1990; Masino and
      Knudsen, 1992b). Inactivation of the OT with lidocaine reduced the size but did
      not eliminate (or change the direction of) the saccades evoked by AGF
      stimulation. The direct anatomical pathway from the archistriatum to the midline
      tegmental nuclei can account for saccades that persist following OT inactivation.
      The similarities between the AGF in barn owls and the FEF in primates suggest
      that the same general plan of anatomical and functional organization supports the
      contribution of the forebrain to gaze control in a wide variety of species.

PMID- 7623142
TI  - Binaural tuning of auditory units in the forebrain archistriatal gaze fields of
      the barn owl: local organization but no space map.
AB  - We identified a region in the archistriatum of the barn owl forebrain that
      contains neurons sensitive to auditory stimuli. Nearly all of these neurons are
      tuned for binaural localization cues. The archistriatum is known to be the
      primary source of motor-related output from the avian forebrain and, in barn
      owls, contributes to the control of gaze, much like the frontal eye fields in
      monkeys. The auditory region is located in the medial portion of the
      archistriatum, at the level of the anterior commissure, and is within the region
      of the archistriatum from which head saccades can be elicited by electrical
      microstimulation (see preceding companion article, Knudsen et al., 1995). Free
      field measurements revealed that auditory sites have large, spatial receptive
      fields. However, within these large receptive fields, responses are tuned sharply
      for sound source location. Dichotic measurements showed that auditory sites are
      tuned broadly for frequency and that the majority are tuned to particular values
      of interaural time differences and interaural level differences, the principal
      cues used by barn owls for sound localization. The tuning of sites to these
      binaural cues is essentially independent of sound level. The auditory properties
      of units in the medial archistriatum are similar to those of units in the optic
      tectum, a structure that also contributes to gaze control. Unlike the optic
      tectum, however, the auditory region of the archistriatum does not contain a
      single, continuous auditory map of space. Instead, it is organized into
      dorsoventral clusters of sites with similar binaural (spatial) tuning. The
      different representations of auditory space in closely related structures in the
      forebrain (archistriatum) and midbrain (optic tectum) probably reflect the fact
      that the forebrain contributes to a wide variety of sensorimotor tasks more
      complicated than gaze control.

PMID- 7623143
TI  - Dopaminergic correlates of motivated behavior: importance of drive.
AB  - In vivo brain microdialysis was used to monitor changes in dopamine (DA) release
      in the nucleus accumbens (NAc) during anticipatory and consummatory components of
      feeding behavior. During 10 daily training sessions, rats were first confined to
      one compartment of a testing chamber for 10 minutes. During this period
      (anticipatory phase) they were prevented from gaining access to a highly
      palatable liquid meal by a wire mesh screen. The screen was then removed and the
      animals were permitted to consume the meal for 20 min (consummatory phase). On
      removal of the screen, the latency to begin drinking decreased and the amount
      consumed increased as a function of days of training, both measures reaching
      asymptotic levels by day 7. Trained animals were implanted with dialysis probes
      in the NAc on day 10, and on day 12 DA release was monitored during the feeding
      session. Compared to controls, trained animals failed to show significantly
      greater increases in accumbal DA release during the anticipatory phase, all
      groups showing small (approximately 10%) increases on being placed in the test
      chamber. In contrast, compared to controls, DA release increased significantly in
      the NAc during consumption of the palatable meal. The magnitude of this increase
      was significantly enhanced (30% vs 71% peak increase) in animals that were 20 hr
      food deprived at the time of testing. The latter animals also showed a
      statistically significant increase (24%) in DA release during the anticipatory
      phase. A subsequent experiment in which consumption of the palatable liquid was
      limited to 5 ml in deprived and nondeprived animals indicated that only part of
      the deprivation-induced potentiation of accumbal DA release could be attributed
      to the larger volume consumed by the deprived animals. That is, the same volume
      and rate of consumption of a small amount of the liquid diet produced a
      significantly greater increase in accumbal DA release in deprived than in
      nondeprived animals (42% vs 23% peak increase). Feeding-induced increases in
      accumbal DA release were not due to postingestional factors as direct injections
      of the liquid diet into the stomach by gavage failed to produce this effect. The
      results of these experiments indicate (1) that consummatory rather than
      anticipatory aspects of feeding are robustly associated with increases in DA
      release in the NAc, and (2) that motivational state can influence the magnitude
      of the neurochemical events that are associated with goal-directed behaviors.

PMID- 7623144
TI  - Lactate released by Muller glial cells is metabolized by photoreceptors from
      mammalian retina.
AB  - The nature of fuel molecules trafficking between mammalian glial cells and
      neurons was explored using acute retinal cell preparations of solitary Muller
      glial cells, Muller cells still attached to photoreceptors (the "cell complex"),
      and solitary photoreceptors. 14C-Molecules in the cell complex, Muller cells, and
      respective baths were quantitated following 30 min incubation in bicarbonate
      buffered Ringer's solution carrying 5 mM 14C(U)-glucose, and substrate preference
      by solitary photoreceptors was assessed by measuring 14CO2 production. Muller
      cells alone metabolized 14C-glucose predominantly to carbohydrate intermediates,
      while the presence of photoreceptors raised proportionately the amount of
      radiolabeling in amino acids. 14C-Lactate was the major carbohydrate found in the
      bath. However, in the presence of photoreceptors, its amount was 70% less than
      that for Muller cells alone. This decrease matched the expected production of
      14CO2 by photoreceptor oxidative metabolism and was antagonized by the addition
      of unlabeled lactate. Moreover, while solitary photoreceptors consumed both
      exogenous 14C-lactate and 14C-glucose, lactate was a better substrate for their
      oxidative metabolism. In the cell complex, the metabolism of amino acids
      increased and illumination affected primarily glutamate and glutamine production:
      the specific activity of glutamate changed in parallel with that of lactate, and
      that of glutamine increased by eightfold in darkness. These results demonstrate
      transfer of lactate from Muller cells to photoreceptors and underscore a
      photoreceptor-dependent modulation of lactate and amino acid metabolism. We
      propose that net production and release of lactate by Muller cells serves to
      maintain their glycolysis elevated and to fuel mitochondrial oxidative metabolism
      and glutamate resynthesis in photoreceptors.

PMID- 7623145
TI  - Response of monkey MST neurons to optic flow stimuli with shifted centers of
      motion.
AB  - Neurons in the dorsal region of the medial superior temporal area (MSTd) have
      previously been shown to respond to the expanding radial motion that occurs as an
      observer moves through the environment. In previous experiments, MSTd neurons
      were tested with radial and circular motion centered in the visual field.
      However, different directions of observer motion, relative to the direction of
      gaze, are accompanied by visual motion centered at different locations in the
      visual field. The present experiments investigated whether neurons that respond
      to radial and circular motion might respond differently when the center of motion
      was shifted to different regions of the visual field. About 90% of the 245
      neurons studied responded differently when the center of motion was shifted away
      from the center of the field. The centers of motion preferred by each neuron were
      limited to one area of the visual field. All parts of the visual field were
      represented in the sample, with greater numbers of neurons preferring centers of
      motion closer to the center of the field. We hypothesize that each of the MSTd
      neurons has a center of motion field with a gradient of preferred centers of
      motion, and that there is an orderly arrangement of MSTd neurons with each region
      of the visual field being represented by a set of neurons. This arrangement
      creates the potential for graded responses from individual neurons for different
      directions of heading as an observer moves through the environment.

PMID- 7623146
TI  - The major delayed rectifier in both Drosophila neurons and muscle is encoded by
      Shab.
AB  - The delayed rectifier K+ current in Drosophila is similar to the classical
      delayed rectifier, originally described by Hodgkin and Huxley. Drosophila
      provides unique tools of mutant analysis to unambiguously determine the genetic
      identity of this native K+ current. We identified the Shab gene as the exclusive
      gene underlying delayed rectifier currents in both muscle and neurons. In
      muscles, a genetic mutation of Shab removes virtually all the whole cell delayed
      rectifier current (IK), while leaving unaltered the transient A-current encoded
      by the Shaker gene. In neurons, the Shab mutation also removes the bulk of IK,
      but leaves unaltered the transient A-current encoded by the Shal gene. Although
      most of the delayed rectifier current is the product of the Shab gene, the Shaw
      gene contributes a small "leak" current to most neurons and muscle cells. Thus,
      in contrast to the A-currents which are encoded by different genes in muscle and
      neuronal cell bodies (Shaker and Shal, respectively), the predominant IK in both
      muscle and neurons is encoded by the same gene (Shab). With the genetic identity
      of IK confirmed, all of the major K+ currents in embryonic Drosophila neurons and
      muscle are now known.

PMID- 7623147
TI  - Electron microscopic analysis of D1 and D2 dopamine receptor proteins in the
      dorsal striatum and their synaptic relationships with motor corticostriatal
      afferents.
AB  - The precise localization of D1 and D2 dopamine receptors within striatal neurons
      and circuits is crucial information for further understanding dopamine
      pharmacology. We have used subtype specific polyclonal and monoclonal antibodies
      against D1 and D2 dopamine receptors to determine their cellular and subcellular
      distributions, their colocalization, and their differential connectivity with
      motor cortical afferents labeled either by lesion-induced degeneration or by
      anterograde transport of biotinylated dextrans. D1 and D2 are primarily expressed
      in medium-sized neurons and spiny dendrites. Axon terminals containing D1 were
      rare whereas D2-immunoreactive axon terminals forming symmetrical synapses with
      dendrites and spines were common. In 2 microns sections, D1 was localized to 53%
      of neurons, and D2 to 48% of neurons, while mixing D1 and D2 antibodies labeled
      78%. By electron microscopy, D1 was localized to 43% of dendrites and 38% of
      spines while D2 was localized to 38% of dendrites and 48% of spines. Combining D1
      and D2 antibodies resulted in the labeling of 88.5% of dendrites and 92.6% of
      spines. Using different chromogens for D1 and D2, colocalization was not
      observed. Ipsilateral motor corticostriatal afferents were primarily axospinous
      and significantly more synapsed with D1 than D2-positive spines (65% vs 47%).
      Contralateral motor corticostriatal afferents were frequently axodendritic and no
      difference in their frequency of synapses with D1 and D2 dendrites and spines was
      observed. These findings demonstrate differential patterns of expression of D1
      and D2 receptors in striatal neurons and axon terminals and their differential
      involvement in motor corticostriatal circuits.

PMID- 7623148
TI  - A novel RING-H2 motif protein downregulated by axotomy: its characteristic
      localization at the postsynaptic density of axosomatic synapse.
AB  - Axonal injury and its repair are common and basic neuropathological processes in
      the CNS, and are composed of a complex of events in a molecular term. In order to
      get a comprehensive understanding of these processes, we isolated several known
      and unknown genes which were up-or downregulated in the facial nucleus after
      transection of the facial nerve by a subtractive/differential screening. Among
      them, we focus on one downregulated gene, named Neurodap1, because this gene
      encodes a novel protein carrying the RING-H2 sequence motif categorized in the
      zinc finger family. Immunoelectron microscopic analysis revealed that the protein
      encoded by Neurodap1, Neurodap1, was distributed mainly on the cytoplasmic side
      of the membranes constituting endoplasmic reticulum and Golgi apparatus,
      supporting the notion of a previously postulated function of RING-H2 motif
      proteins, that is, involvement in the protein sorting machinery. More
      interestingly, Neurodap1 was also bound to the postsynaptic density (PSD) region
      of axosomatic synapses. This fact suggests that Neurodap1 is associated with a
      specific system sorting proteins to PSD. Therefore, Neurodap1, a newly identified
      protein as an axotomy-suppressed gene product, might play a significant role in
      synaptic communication and plasticity through the control of the formation of PSD
      for maintaining vital functions of nerve cells.

PMID- 7623149
TI  - Dynamics of learning and recall at excitatory recurrent synapses and cholinergic
      modulation in rat hippocampal region CA3.
AB  - Hippocampal region CA3 contains strong recurrent excitation mediated by synapses
      of the longitudinal association fibers. These recurrent excitatory connections
      may play a dominant role in determining the information processing
      characteristics of this region. However, they result in feedback dynamics that
      may cause both runaway excitatory activity and runaway synaptic modification.
      Previous models of recurrent excitation have prevented unbounded activity using
      biologically unrealistic techniques. Here, the activation of feedback inhibition
      is shown to prevent unbounded activity, allowing stable activity states during
      recall and learning. In the model, cholinergic suppression of synaptic
      transmission at excitatory feedback synapses is shown to determine the extent to
      which activity depends upon new features of the afferent input versus components
      of previously stored representations. Experimental work in brain slice
      preparations of region CA3 demonstrates the cholinergic suppression of synaptic
      transmission in stratum radiatum, which contains synapses of the longitudinal
      association fibers.

PMID- 7623150
TI  - Peripheral benzodiazepine receptors are colocalized with activated microglia
      following transient global forebrain ischemia in the rat.
AB  - In mammalian brain the expression of peripheral benzodiazepine receptors (PBRs)
      can be markedly induced following different types of neuronal injury. PBRs are
      believed to be expressed on non-neuronal cells in the brain, yet the specific
      cell type that expresses these receptors following CNS insult has not been
      defined. In the present study, we investigated the effects of transient global
      forebrain ischemia on PBRs by autoradiographic localization of 3H-PK11195
      binding. The distribution of PBRs was compared to glial fibrillary acidic protein
      (GFAP) as a marker for astrocytes and OX42 as a marker for microglia. Five to 6 d
      following four-vessel occlusion (4-VO), an increase in PBRs was seen in the CA1
      region of all 15 brains examined. In brains from rats subjected to 4-VO,
      microglia were selectively activated in stratum pyramidale of the CA1 layer. In
      contrast, astrocytes appeared to be activated in multiple hippocampal cell layers
      including stratum radiatum and stratum oriens. Activated astrocytes were also
      found in regions that did not exhibit increased 3H-PK11195 binding. In some
      brains, selected regions of secondary lesion, specifically necrotic thalamic
      nuclei and the isocortex were found to be strongly immunoreactive for OX42 but
      lacked GFAP immunoreactive cells. In adjacent sections, these same regions
      displayed high densities of 3H-PK1195 binding. These observations lend further
      support to the application of 3H-PK11195 binding as a marker of neuronal injury
      in the brain. Furthermore, the data strongly suggest that activated microglia
      rather than astrocytes express PBRs following ischemic insults.

PMID- 7623151
TI  - Trans-synaptic regulation of NMDA receptor RNAs during optic nerve regeneration.
AB  - A goldfish NMDA receptor (NMDAR) cDNA was used to analyze NMDAR RNA expression
      during optic nerve regeneration. Following crush of the optic nerve, NMDAR RNA
      levels initially decrease and then increase in retinal ganglion cells. This
      latter increase corresponds with the time when ganglion cell axons are forming
      stable connections with their targets in the optic tectum. NMDAR RNA stability
      assays indicate that the increase in this RNA is largely a result of increased
      NMDAR gene expression. This increase requires return of electrical activity in
      the regenerating axons, interaction between ganglion cell axons and their targets
      in the optic tectum, and functional NMDARs in the postsynaptic tectal cells.
      These requirements for induction of presynaptic NMDAR RNA are similar to those
      proposed for synapse stabilization during development and regeneration of the
      visual system and during long-term potentiation (LTP) in the hippocampus.

PMID- 7623152
TI  - NMDA receptor subunit mRNA expression by projection neurons and interneurons in
      rat striatum.
AB  - N-Methyl-D-aspartate (NMDA) receptors are enriched in the neostriatum and are
      thought to mediate several actions of glutamate including neuronal excitability,
      long-term synaptic plasticity, and excitotoxic injury. NMDA receptors are
      assembled from several subunits (NMDAR1, NMDAR2A-D) encoded by five genes;
      alternative splicing gives rise to eight isoforms of subunit NMDAR1. We studied
      the expression of NMDA receptor subunits in neurochemically identified striatal
      neurons of adult rats by in situ hybridization histochemistry using a double
      labeling technique. Enkephalin-positive projection neurons, somatostatin-positive
      interneurons, and cholinergic interneurons each have distinct NMDA receptor
      subunit phenotypes. Both populations of striatal interneurons examined express
      lower levels of NMDAR1 and NMDAR2B subunit mRNA than enkephalin-positive neurons.
      The three striatal cell populations differ also in the presence of markers for
      alternatively spliced regions of NMDAR1, suggesting that interneurons
      preferentially express NMDAR1 splice forms lacking one (cholinergic neurons) or
      both (somatostatin-positive neurons) alternatively spliced carboxy-terminal
      regions. In addition, somatostatin- and cholinergic-, but not enkephalin-positive
      neurons express NMDAR2D mRNA. Thus, these striatal cell populations express
      different NMDAR-subunit mRNA phenotypes and therefore are likely to display NMDA
      channels with distinct pharmacological and physiological properties. Differences
      in NMDA receptor expression may contribute to the relative resistance of striatal
      interneurons to the neurotoxic effect of NMDA receptor agonists.

PMID- 7623153
TI  - Lesions of the fornix but not the entorhinal or perirhinal cortex interfere with
      contextual fear conditioning.
AB  - The effects of entorhinal cortex lesions, combined entorhinal and perirhinal
      cortex lesions, and fornix lesions on the conditioning of fear responses
      (freezing) to contextual stimuli were examined using a conditioning procedure
      known to produce hippocampal-dependent contextual conditioning. Lesions of the
      entorhinal and or entorhinal plus perirhinal cortex did not disrupt contextual
      conditioning, but lesions of the fornix did. None of the lesions affected
      conditioning to an explicit conditioned stimulus. Given that the entorhinal
      cortex is the primary linkage between the neocortex and the hippocampus and that
      the fornix is the primary linkage with subcortical structures, subcortical inputs
      to and outputs of the hippocampus appear to be sufficient to mediate contextual
      fear conditioning. As a result, the presumption that neocortical information is
      required for contextual fear conditioning, and perhaps other hippocampal
      dependent functions, should be reevaluated.

PMID- 7623154
TI  - Intraventricular administration of antibodies to nerve growth factor retards
      kindling and blocks mossy fiber sprouting in adult rats.
AB  - Repeated subconvulsive electrical stimulation of certain areas of the forebrain
      leads to kindling, a progressive and permanent amplification of evoked
      epileptiform activity, which is a model for human temporal lobe epilepsy. Recent
      studies have shown that kindling induces synthesis of nerve growth factor (NGF)
      and brain-derived neurotrophic factor (BDNF) but not neurotrophin-3 (NT-3) in the
      hippocampus and cortex. Kindling also elicits mossy fiber sprouting and
      functional synaptogenesis in the supragranular layer, the hilus, and the CA3
      region of the hippocampus. Intraventricular administration of antibodies to NGF
      has been shown to effectively block septohippocampal sprouting in the adult rat,
      and has been reported to retard amygdaloid kindling. In the present study, we
      have investigated the possible role of NGF in both kindling and kindling
      associated sprouting. We have confirmed a kindling-induced sprouting of the mossy
      fibers into the stratum oriens of the CA3 region of the hippocampus, utilizing a
      new semiquantitative method of analysis based on Timm staining. Previous studies
      found no overt signs of hippocampal damage with this kindling paradigm,
      indicating that the increased Timm staining likely reflects a purely activity
      induced sprouting. Intraventricular infusion of affinity-purified anti-NGF IgGs
      (which cross-react with NT-3 but not BDNF) resulted in both significant
      retardation of kindling and inhibition of the kindling-induced mossy fiber
      sprouting. The findings suggest a role for NGF in both these phenomena.

PMID- 7623155
TI  - Different forms of synaptic plasticity in somatosensory and motor areas of the
      neocortex.
AB  - We have studied vertical synaptic pathways in two cytoarchitectonically distinct
      areas of rat neocortex--the granular primary somatosensory (SI) area and the
      agranular primary motor (MI) area--and tested their propensity to generate long
      term potentiation (LTP), long-term depression (LTD), and related forms of
      synaptic plasticity. Extracellular and intracellular responses were recorded in
      layer II/III of slices in vitro while stimulating in middle cortical layers (in
      or around layer IV). Under control conditions, 5 Hz theta-burst stimulation
      produced LTP in the granular area, but not in the agranular area. Agranular
      cortex did generate short-term potentiation that decayed within 20 min. Varying
      the inter-burst frequency from 2 Hz to 10 Hz reliably yielded LTP of 21-34% above
      control levels in granular cortex, but no lasting changes were induced in
      agranular cortex. However, the agranular cortex was capable of generating LTP if
      a GABAA receptor antagonist was applied locally at the recording site during the
      induction phase. In contrast to LTP, an identical form of homosynaptic LTD could
      be induced in both granular and agranular areas by applying low frequency
      stimulation (1 Hz for 15 min) to the middle layers. Under control conditions,
      both LTP and LTD were synapse-specific; theta-burst or low-frequency stimulation
      in the vertical pathway did not induce changes in responses to stimulation of a
      layer II/III horizontal pathway. Application of the NMDA receptor antagonist D-2
      amino-5-phosphonovaleric acid (AP5) blocked the induction of both LTP and LTD in
      granular and agranular cortex. In the presence of AP5, low-frequency conditioning
      stimuli yielded a short-term depression in both areas that decayed within 10-15
      min. Nifedipine, which blocks L-type, voltage-sensitive calcium channels,
      slightly depressed the magnitudes of LTP and LTD but did not abolish them.
      Synaptic responses evoked during theta-burst stimulation were strikingly
      different in granular and agranular areas. Responses in granular cortex were
      progressively facilitated during each sequence of 10 theta-bursts, and from
      sequence-to-sequence; in contrast, responses in agranular cortex were stable
      during an entire theta-burst tetanus. The results suggest that vertical pathways
      in primary somatosensory cortex and primary motor cortex express several forms of
      synaptic plasticity. They were equally capable of generating LTD, but the
      pathways in somatosensory cortex much more reliably generated LTP, unless
      inhibition was reduced. LTP may be more easily produced in sensory cortex because
      of the pronounced synaptic facilitation that occurs there during repetitive
      stimulation of the induction phase.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7623156
TI  - Neurotransmitter receptors of starburst amacrine cells in rabbit retinal slices.
AB  - The receptor pharmacology of cholinergic ("starburst") amacrine cells was studied
      in a newly developed rabbit retinal slice preparation with whole-cell patch
      clamp. Displaced starburst cells were labeled with the fluorescent dye 4,6
      diamidino-2-phenylindole (DAPI), and their dendritic morphology was identified in
      the slice with Lucifer yellow. Under conditions in which synaptic transmission
      was blocked by Cd2+, starburst cells responded vigorously to the bath-applied
      neurotransmitters GABA, glycine, and glutamate. The response to GABA consisted of
      an inward current and an increase in noise, which could be mimicked by the GABAA
      agonists muscimol and trans-4-aminocrotonic acid (TACA), but not by the GABAB
      agonist baclofen or the GABAC agonist cis-4-aminocrotonic acid (CACA). The GABA
      evoked currents were reversibly inhibited by bicuculline and picrotoxin and had a
      reversal potential close to the chloride equilibrium potential. Noise analysis of
      GABA-activated whole-cell currents yielded elementary conductance estimates of
      12.5 pS. Glycine (30-200 microM) also activated a Cl- conductance in starburst
      cells, which could be completely blocked by strychnine. The non-NMDA agonists
      kainate (KA, 30-100 microM) and alpha-amino-3-hydroxy-5-methylisoxazole-4
      propionic acid (AMPA, 60 microM) evoked robust responses, which were reversibly
      blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), and which reversed near
      the equilibrium potential for cations. NMDA coapplied with glycine in salines
      free of Cd2+ and Mg2+ elicited small but detectable responses. The I/V relation
      of the NMDA-evoked response showed a characteristic "J"-shaped region in a saline
      containing 1 mM Mg2+ and 0 Cd2+, indicating that NMDA receptors were present
      directly on starburst cells. This was consistent with our finding that whole-cell
      currents evoked by KA and NMDA had different noise characteristics. These results
      place new constraints on models of starburst cell function and suggest that GABA
      mediated inhibition of the starburst cell itself may play an important role in
      directional selectivity in the retina.

PMID- 7623157
TI  - Response of serotonergic caudal raphe neurons in relation to specific motor
      activities in freely moving cats.
AB  - Serotonergic neuronal responses during three specific motor activities were
      studied in nuclei raphe obscurus (NRO) and raphe pallidus (NRP) of freely moving
      cats by means of extracellular single-unit recordings. Responses to treadmill
      induced locomotion were primarily excitatory, with 21 of 24 neurons displaying
      increased firing rates, directly related to treadmill speed. Individual
      regression analyses determined three response patterns: maximal activation at low
      speed (0.25 m/sec), augmentation of neuronal activity only at high treadmill
      speed (0.77 m/sec), and a linear increase. A smaller fraction of NRO and NRP
      serotonergic neurons (6 of 27) also responded to hypercarbic ventilatory
      challenge with increased firing rates. The magnitude of neuronal response was
      dependent upon the fraction of inspired CO2 and was related to ventilatory motor
      output, specifically, inspiratory amplitude. A subgroup of neurons responsive to
      hypercarbia in wakefulness demonstrated significant reductions in neuronal
      response to hypercarbia in slow-wave sleep. Finally, unit activity for 12 of 29
      cells increased in response to spontaneous feeding, displaying two distinct
      patterns of neuronal response in relation to onset and termination of feeding:
      rapid activation and deactivation versus a gradual increase and decrease. More
      than half of the cells studied under all three conditions were responsive to more
      than one motor task. These results indicate that serotonergic caudal raphe
      neurons are responsive to specific motor system challenges, with many neurons
      responsive to multiple motor tasks, and that the responsiveness of serotonergic
      neurons to at least one motor task, hypercarbic ventilatory challenge, is state
      dependent.

PMID- 7623158
TI  - Association and colocalization of K+ channel alpha- and beta-subunit polypeptides
      in rat brain.
AB  - Recent cloning of auxiliary subunits associated with voltage-gated ion channels
      and their subsequent coexpression with the channel forming alpha-subunits has
      revealed that the expression level, gating and conductance properties of the
      expressed channels can be profoundly affected by the presence of an auxiliary
      subunit polypeptide. In the present study, we raised antibodies against the beta
      subunit associated with the bovine dendrotoxin sensitive K(+)-channel complex and
      used these antibodies to characterize the related beta-subunit polypeptides in
      rat brain. The anti-beta-subunit antibodies displayed a specific reaction on
      immunoblots of rat brain membranes with a major 38 kDa polypeptide, and a minor
      41 kDa polypeptide, which correspond closely to the predicted sizes of the Kv
      beta 2 and Kv beta 1 beta-subunit polypeptides, respectively, recently cloned
      from rat brain. Reciprocal coimmunoprecipitation experiments revealed that the
      beta-subunit polypeptides are associated with Kv1.2 and Kv1.4, but not Kv2.1,
      alpha-subunits. Immunohistochemical staining revealed that the beta-subunit
      polypeptides were widely distributed in adult rat brain. Moreover, the cellular
      distribution of beta-subunit immunoreactivity corresponded closely with
      immunoreactivity for Kv1.2, and to a lesser extent Kv1.4, but not with Kv2.1.
      These results suggest that neuronal mechanisms may exist to direct the selective
      interaction of K+ channel alpha- and beta-subunit polypeptides, and that the
      properties of K+ channels in specific subcellular domains may be regulated by the
      formation of heteromultimeric K+ channel complexes containing specific
      combinations of alpha- and beta-subunits.

PMID- 7623159
TI  - Elevated body swing test: a new behavioral parameter for rats with 6
      hydroxydopamine-induced hemiparkinsonism.
AB  - Parkinson's disease is characterized by a depletion of dopamine (DA) neurons in
      the nigrostriatal pathway. Stereotaxic injections of 6-hydroxydopamine (6-OHDA),
      a selective neurotoxin, into either the medial forebrain bundle or the substantia
      nigra result in a massive DA denervation of the nigrostriatal pathway. Following
      unilateral nigrostriatal DA depletion, hemiparkinsonian animals develop a
      stereotypical rotational behavior when challenged with DA agonists such as
      apomorphine. The drug-induced rotational behavior has been widely used as the
      behavioral index of hemiparkinsonian animals, but it has some limitations.
      Although asymmetries in the rotational behavior may indicate an imbalance of DA
      contents and release capacity in the bilateral nigrostriatal pathway, the
      behavior is a pharmacological reaction. Accordingly, the drug-induced rotation
      test is subject to sensitization effects. The present study proposes the elevated
      body swing test (EBST) as a measure of asymmetrical motor behavior of
      hemiparkinsonian animals in a drug-free state. The EBST simply involves elevating
      the animal by handling its tail and recording the frequency and direction of the
      swing behavior. Unilateral nigral 6-OHDA-lesioned rats exhibited significant
      biased swing activity with the direction contralateral to the lesioned side,
      corresponding to the direction of apomorphine-induced rotations. A 30 sec EBST
      was noted as the peak time for biased swing activity. At 7 d postlesion (the
      start of testing), and every week thereafter for a period of 2 months, a fairly
      stable biased swing activity level was observed. At 1 and 2 months postlesion,
      the same animals were also challenged with apomorphine.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7623160
TI  - D1 receptors modulate glutamate transmission in the ventral tegmental area.
AB  - Perfusion of the D1 agonist, SKF-82958, through a microdialysis probe implanted
      in the ventral tegmental area produced a dose-dependent increase in extracellular
      glutamate and GABA. The increase in extracellular glutamate occurred at
      approximately 30x lower dose than the elevation in GABA. The increase in
      extracellular glutamate by SKF-82958 was blocked by coperfusion of the D1
      antagonist, SCH-23390, and was not mimicked by perfusion of the D2/3 agonist,
      quinpirole, into the ventral tegmental area. In contrast, the elevation in
      extracellular GABA was insensitive to blockade by SCH-23390. Systemic
      administration of cocaine (15 mg/kg, i.p.) produced a rapid elevation in
      extracellular glutamate lasting for 20 min that was prevented by pretreating the
      ventral tegmental area with SCH-23390. In contrast, acute cocaine produced a
      reduction in extracellular GABA content in the ventral tegmental area that was
      not affected by SCH-23390. These data indicate that the stimulation of D1
      receptors in the ventral tegmental area increases the release of glutamate and
      that increasing extracellular levels of somatodendritic dopamine by systemic
      cocaine can mimic this effect.

PMID- 7623161
TI  - Thrombin receptor activation protects neurons and astrocytes from cell death
      produced by environmental insults.
AB  - Thrombin is a multifunctional serine protease that is rapidly produced from
      prothrombin at sites of tissue injury and catalyzes the final steps in blood
      coagulation. Thrombin also regulates gene expression and process outgrowth in
      neurons and astrocytes and stimulates proliferation of astrocytes. Since thrombin
      is produced immediately upon breakdown of the blood-brain barrier we examined its
      effects on astrocytes and neurons cultured under conditions which resemble those
      found in vivo following cerebrovascular injury. These studies showed that
      thrombin markedly protected rat primary astrocytes from cell death induced by
      hypoglycemia or oxidative stress. Thrombin also protected rat primary hippocampal
      neurons from cell death produced by hypoglycemia or growth supplement
      deprivation. Synthetic peptides which directly activate the thrombin receptor
      also protected astrocytes and neurons from these environmental insults,
      demonstrating that the thrombin effects were mediated through the thrombin
      receptor. In contrast to these results with stressed cells, high concentrations
      of thrombin killed both astrocytes and neurons cultured under normal conditions.
      All of the effects of thrombin on astrocytes and neurons were blocked by the
      brain thrombin inhibitor, protease nexin-1 (PN-1). This shows that the effects
      required the proteolytic activity of thrombin and is consistent with the known
      proteolytic mechanism by which thrombin activates its receptor. These results
      indicate that thrombin and PN-1 may regulate the viability of both astrocytes and
      neurons in early moments following trauma to the CNS or other conditions that
      alter the blood-brain barrier.

PMID- 7623162
TI  - Induction and reversal of long-term potentiation by low- and high-intensity theta
      pattern stimulation.
AB  - Reversal of long-term potentiation by low-frequency stimulation is often referred
      to as depotentiation. However, it is not clear whether depotentiation induced by
      low-frequency stimulation and long-term depression (LTD) induced by similar
      stimuli are distinct phenomena. We have performed a series of experiments in area
      CA1 of rat hippocampal slices in which a single pattern of theta-burst (TB)
      stimulation (Larson, et al., 1986; Staubli and Lynch, 1987) was found to produce
      either LTP or reversal of LTP depending on the intensity of the stimulation. TB
      stimulation (10 trains consisting of 4 pulses at 100 Hz, 200 msec apart)
      delivered at test pulse-intensity induced LTP. However, the same stimulation
      delivered at a higher intensity (10 times that of the test pulse, evoking a
      maximal response) did not induce LTP or depression of control responses, but
      produced lasting depression of previously potentiated responses. This reversal of
      LTP (TB depotentiation) was observed when the stimulus was delivered between 0.5
      and 110 min after induction of LTP. TB depotentiation was reversible, cumulative
      and saturable when high-intensity TB trains were delivered in succession. TB
      depotentiation was also blocked by antagonists at NMDA receptors. Low-frequency
      (1 Hz) stimulation induced LTD, indicating that responses were not already
      maximally depressed. In addition, high-intensity TB stimulation did not reverse
      LTD. These results suggest that depotentiation induced by maximal TB stimulation
      and LTD induced by low-frequency stimulation are distinct phenomena, yet share
      some characteristics common to forms synaptic plasticity mediated by NMDA
      receptor activation.

PMID- 7623163
TI  - Prostaglandins facilitate peptide release from rat sensory neurons by activating
      the adenosine 3',5'-cyclic monophosphate transduction cascade.
AB  - Prostaglandins sensitize sensory neurons to activation by mechanical, thermal and
      chemical stimuli. This sensitization also results in an increase in the stimulus
      evoked release of the neuroactive peptides, substance P and calcitonin gene
      related peptide from sensory neurons. The cellular transduction cascade
      underlying the prostaglandin-induced augmentation of peptide release is not
      known. Therefore, we examined whether the sensitizing action of prostaglandins on
      peptide release from sensory neurons grown in culture is mediated by the second
      messenger, adenosine 3', 5' cyclic monophosphate (cAMP). Prostaglandin E2 and
      carba prostacyclin (a stable analog of prostaglandin I2) significantly increase
      the content of cAMP-like immunoreactive substance (icAMP) in the sensory neuron
      cultures at concentrations that also augment the bradykinin- or capsaicin-evoked
      release of peptides. Furthermore, pretreating sensory neurons with agents that
      increase intracellular cAMP mimics the sensitizing action of prostaglandins.
      Exposing cultures to either forskolin (0.1-10 microM), cholera toxin (1.5
      micrograms), or 8-bromo-cAMP (100 microM) results in a significant enhancement of
      the bradykinin- or capsaicin-stimulated release of both substance P-like and
      calcitonin gene-related peptide-like immunoreactive substances. Pretreating
      sensory neurons with the adenylyl cyclase inhibitor, 9-tetrahydro-2-furyl adenine
      (5 mM), abolishes the prostaglandin-induced increases in icAMP content and
      attenuates the prostaglandin E2 or carba prostacyclin enhancement of the evoked
      release of calcitonin gene-related peptide-like immunoreactive substance. These
      results demonstrate that the cAMP transduction cascade mediates the sensitizing
      actions of prostaglandins on peptide release from sensory neurons.

PMID- 7623164
TI  - Relation of mild-to-moderate malnutrition to human development: correlational
      studies.
AB  - The present review focuses on the relation to human behavior and development of
      anthropometric or dietary indexes of mild-to-moderate malnutrition. The primary
      goal of the review is to integrate previous research findings with current
      findings from correlational studies conducted over the past decade. From this
      integration, the following conclusions may be drawn: 1) Chronic, mild postnatal
      malnutrition is associated with a variety of cognitive and behavioral deficits
      across the life span. The role of prenatal malnutrition in this process is less
      clear. 2) To understand the role chronic mild malnutrition plays in behavior and
      development, it is necessary to move beyond protein-calorie deficits to consider
      the role of intake of animal source foods and specific micronutrients such as
      iron, zinc and B vitamins. 3) Chronic mild malnutrition is embedded in a host of
      other biological and psychosocial risk factors. As a result, chronic mild
      malnutrition appears to be a necessary but insufficient condition for producing
      behavioral deficits. 4) The salience of chronic mild malnutrition as a risk
      factor is accentuated when other psychosocial-contextual risk factors are also
      present or when multiple low-level nutrient deficits are interacting. Suggestions
      for future research directions include an emphasis on interactions between
      nutrients and between specific psychosocial and nutritional risk factors; the
      ways in which individual (e.g., gender) or cultural characteristics can moderate
      nutrition development relations; and a broader range of populations, such as
      sibling or elderly caregivers, and outcome variables, such as social-emotional
      development, temperament and mental health.

PMID- 7623165
TI  - Developmental zinc deficiency and behavior.
AB  - The majority of studies of developmental zinc deficiency and behavior were
      conducted in laboratory animals, primarily rats and rhesus monkeys. Effects on
      food intake complicate interpretation of experiments using severe zinc
      deficiency. Severe zinc deficiency in rats during the period of rapid brain
      growth has similar effects to protein calorie malnourishment during this period,
      including altered emotionality and food motivation. When behavior is tested
      during a period of zinc deprivation in immature animals, lethargy (reduced
      activity and responsiveness) is a prominent characteristic, but learning,
      attention and memory are also affected. The few supplement studies available in
      children did not report effects on behavior. Although zinc has multiple roles in
      brain function, considerable brain sparing occurs in zinc deficiency, and
      peripheral mechanisms of altered behavior also need to be considered.

PMID- 7623166
TI  - Human milk and breast feeding for optimal mental development.
AB  - Human milk has been characterized as the optimal food for human growth and
      development because of its nutritional, antiinfective and biological properties.
      Research conducted over the past decades provides further evidence on the
      uniqueness of human milk feeding for optimal brain development. The recognition
      of specific functions for the long chain essential fatty acids present in human
      milk as key components of neural membranes necessary for optimal brain
      development has provided a biological basis for this phenomenon. In addition the
      act of breast feeding provides unique mother-infant interactions opportunities
      that may have important implications for infant growth and development. These
      findings may have special relevance to populations in developing countries
      because this provides yet other very strong reasons to favor human milk feeding.

PMID- 7623167
TI  - Policy implications of new scientific knowledge.
AB  - Recent research findings have augmented the nutrition variable to a higher
      category of importance than previously appreciated. Inadequate nutrition can
      impair cognitive development and is associated with educational failure among
      impoverished children. This suggests that poor nutrition interferes with the
      formation of human capital, the cornerstone of a nation's social and economic
      development. Even temporary food shortages can produce adverse outcomes in
      developed as well as developing countries. The long-held concept of a critical
      period of brain development has been modified in light of the new understanding
      that developmental and morphological plasticity are far greater than previously
      recognized. This knowledge does not mean that there are no lasting adverse
      outcomes, but that from a policy perspective, intervention and rehabilitation can
      play crucial roles. This article highlights the relevance of this evidence to
      social and health programs and policies.

PMID- 7623168
TI  - Experimental study of early diagnosis and treatment of fat embolism syndrome.
AB  - An experimental animal model has been established using i.v. fat injection to
      mimic fat embolism syndrome (FES). Fourteen healthy mongrel dogs who were
      administered 0.7 ml/kg of fluid marrow fat obtained from the long bone marrow
      cavity of mongrel dogs were divided into control and therapeutic groups. The
      therapeutic group (n = 7) was given dexamethasone (1.0 mg/kg) and repeated every
      6 h i.v. During 48 h of observation, blood gas analysis and frozen sections were
      performed on blood samples collected from the pulmonary vessels by a floating
      catheter and from a peripheral vein at different time intervals. The frozen
      sections were stained with Oil Red O. Positive results were seen 2 h after fat
      injection in both pulmonary and peripheral blood samples of both control and
      therapeutic groups. By computer image analysis, the average median number of fat
      droplets per section and the average median diameter of fat droplets in pulmonary
      blood of the control group were found to be significantly higher and larger than
      were those of the therapeutic group. The average median number and diameter of
      fat droplets in pulmonary blood were significantly higher and larger than were
      those of peripheral blood in both control and therapeutic groups. These findings
      correlated well with blood gas changes and the clinical appearance of the
      experimental animals. The fat droplets from pulmonary or peripheral blood as
      demonstrated by Oil Red O staining in combination with blood gases changes [PaO2
      < 7.99 KPa, difference between the alveolar and arterial oxygen tension (P(A -
      a)O2) > 6.09 KPa] may be a rapid method for screening of an earlier diagnosis of
      FES.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7623169
TI  - Acute posterior fracture dislocations of the shoulder treated with the Neer
      modification of the McLaughlin procedure.
AB  - Posterior dislocation of the shoulder may be associated with an anteromedial
      impaction fracture rendering the shoulder unstable in internal rotation. The
      modified McLaughlin procedure as described by Neer involves transplanting the
      lesser tuberosity with the attached subscapularis tendon into the anteromedial
      defect. We have used this procedure acutely (from the day of injury to 10 days
      postinjury) in seven shoulders. All patients were unstable in internal rotation
      and had an anteromedial impaction fracture occupying 25-40% of the articular
      surface. This technique provides good stability, enables immediate active range
      of motion, and allows the patient to rapidly return to activities of daily
      living.

PMID- 7623170
TI  - Compression plating versus hackethal nailing in closed humeral shaft fractures
      failing nonoperative reduction.
AB  - Prospectively, 40 patients with an average age of 45 (20-65) with closed
      transverse fractures of the middle one-third of the humerus without associated
      radial nerve palsy were treated. All had failed nonoperative reduction and were
      then operated on with either compression plating or intramedullary fixation with
      Hackethal nails and a postoperative ready-made fracture brace. These surgeries
      were performed at an average of 7 days (4-10) after closed reduction. The
      Hackethal nailing group consisted of 20 patients (17 men, 3 women) with a mean
      age of 47 years (22-64); within 2 days after surgery the patients were allowed to
      begin active and passive range-of-motion exercises of the elbow and the shoulder
      with the arm protected by a ready-made fracture brace; the average follow-up
      period for this group was 18 months (12-50). These patients (with one exception)
      required a second surgical procedure with a second anesthesia to remove the
      symptomatic nails; moreover, they had to be protected in a brace for 6 months.
      The compression plate group consisted of 20 patients (14 men, 6 women) with a
      mean age of 45 years (20-65); within 2 days after surgery the patient was allowed
      to begin the same rehabilitation program; in this group no braces were used
      postoperatively. All fractures treated with Hackethal nailing healed except for
      one delayed union. Functional results in this group were 12 excellent, 4 good, 1
      fair, and 3 poor. All fractures treated by compression plating healed except in
      one case of delayed union.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7623171
TI  - A biomechanical comparison of two methods of fixation of fractures of the
      forearm.
AB  - In this study two different types of forearm internal fracture fixations were
      compared: limited-contact dynamic compression (DC) plates and fluted
      intramedullary (IM) rods. Eight matched pairs of intact forearms, consisting of
      the distal part of the humerus, elbow joint, radius, ulna, interosseus membrane,
      wrist joint, and metacarpals, were randomly separated into two groups. Each was
      placed into a custom-designed apparatus and subjected to medial bending,
      supination, pronation, axial compression, and distraction loading. Loads were
      applied by a materials testing system, and angular displacements were measured by
      inclinometers. The procedure consisted of first testing specimens intact, then
      retesting after osteotomizing and fixing the radius with either a plate or rod in
      half of the group and retesting after osteotomizing and fixing the ulna in the
      other half. Testing was continued by osteotomizing and remaining intact bone to
      create a two-bone fracture, fixing them, and retesting after creating a 5-mm gap
      at the osteotomy sites. These tests showed that the intact ulna contributes more
      to forearm stability in bending and torsion than does the radius. Therefore, if
      the radius is fractured but the ulna remains intact, IM rodding will produce
      constructs with greater stiffnesses, particularly in torsion, than if the ulna is
      fractured and the radius is intact. In the case of a two-bone fracture,
      implantation of rods will result in a construct with significantly less stiffness
      in torsion, as well as distraction and compression (in the case of a fracture
      gap), than if the fractures were plated.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7623172
TI  - Early results of percutaneous iliosacral screws placed with the patient in the
      supine position.
AB  - The operative management of pelvic ring fractures and dislocations is difficult.
      Posterior pelvic ring disruptions are often associated with severe soft-tissue
      injuries and high infection rates. Percutaneous iliosacral screw fixation of the
      posterior pelvis has become popular with improved fluoroscopic imaging
      techniques. The percutaneous iliosacral screw technique after closed reduction of
      the posterior pelvic disruption minimally violates the soft-tissue envelope and
      should diminish both the operative blood loss and infection rate. The early
      results and complications are documented in our first 68 patients.

PMID- 7623173
TI  - Quality of reduction and cortical screw support in femoral neck fractures. An
      analysis of 72 fractures with a new computerized measuring method.
AB  - The aim of this study was to compare the quality of reduction and the position of
      the fixating screws with the rate of union in 72 femoral neck fractures. The
      degree of fracture displacement after reduction and the position of the two
      fixating screws were determined with a new computerized measuring method that
      compensates for the variations in hip rotation in routine radiographs. All 13
      nondisplaced fractures united. Sixteen of 18 fractures healed in the group of
      displaced fractures where both the fixating screws were placed within 3 mm from
      the femoral neck cortex, compared with 13 of 22 healed fractures in the group
      where only one screw had the same close contact with the femoral neck cortex (p <
      0.05). Nonunion developed in all five displaced fractures where none of the two
      fixating screws were placed within 3 mm from the femoral neck cortex. The quality
      of reduction did not affect the healing rate; however, the number of poorly
      reduced fractures was only 10%. The results of this study underline the
      importance of achieving cortical support for the fixating screws in femoral neck
      fracture surgery.

PMID- 7623174
TI  - Structural allografts for reconstruction of lower extremity open fractures with
      10 centimeters or more of acute segmental defects.
AB  - Long-term results on the use of structural allografts (> or = 10 cm) to
      reconstruct large skeletal defects sustained during high-energy, open lower
      extremity fractures have not been reported. Eight patients are retrospectively
      reviewed at postallograft time periods ranging from 18 to 93 months. Two patients
      required reoperation for noninfectious causes, and each healed uneventfully. Four
      individuals developed infectious complications, but only one required complete
      allograft removal (amputation). The others remain infection free at follow-up.
      Using any of three different rating systems, excellent functional outcome results
      from this method of reconstruction in an otherwise exceptionally challenging
      extremity for limb salvage.

PMID- 7623175
TI  - A simple technique for insertion of distal screws into interlocking nails.
AB  - Placement of distal interlocking screws into femoral and tibial nails is an
      exacting technique. Many techniques are described, each with their advantages and
      disadvantages. We describe an alternative technique using the "third point in
      space." This method has been successfully used in > 30 cases. It is universal,
      reproducible, and inexpensive, avoiding the use of distal targeting guides,
      expensive radiolucent drills, or visual estimations of alignment.

PMID- 7623176
TI  - Total knee replacement including a modular distal femoral component in elderly
      patients with acute fracture or nonunion.
AB  - Distal femoral fracture or nonunion in elderly patients with osteopenic bone and
      coexisting gonarthrosis poses a difficult treatment challenge. Open reduction and
      internal fixation with or without the use of bone cement may not provide
      sufficient stabilization, requires a prolonged period of weightbearing
      restrictions, and does not address preexisting knee arthrosis. We report five
      patients, three with distal femoral nonunion, two with acute distal femoral
      fracture, and all with concomitant gonarthrosis treated with total knee
      replacement including a modular distal femoral component [distal femoral
      replacement (DFR)]. In this group of patients, modular DFR provided immediate
      pain relief and allowed early weightbearing and aggressive rehabilitation. We
      recommend this treatment modality in selected osteopenic elderly patients with
      difficult distal femoral reconstructive problems and coexisting gonarthrosis.

PMID- 7623177
TI  - Repair of patellar tendon disruptions without hardware.
AB  - Acute repair of disruptions of the knee extensor mechanism is indicated to
      reestablish extensor continuity and allow for early motion. This study reviews
      the results of acute primary repair of patellar tendon ruptures augmented by a
      nonabsorbable polyester tape (Mersilene; Ethicon, Inc.) followed by immediate
      mobilization. Twenty-four patients with disruptions of their patellar tendons
      were treated using the described technique. The ruptured tendon was initially
      approximated using an end-to-end suture repair with no. 5 Ticron suture in a
      whipstitch manner. An O Vicryl suture was used to approximate the free tendon
      edges. A 5-mm Mersilene tape was then used in a cerclage manner to augment and
      protect the repair. Postsurgery, passive range of motion (ROM) was begun
      immediately in the knees with isolated injury or in those patients whose
      concomitant injuries would allow for early motion. Using clinical and
      radiographic criteria, follow-up evaluations of 19 patients were performed at an
      average of 22.4 months. In patients with isolated injuries, active ROM was from 0
      degrees extension to 132 degrees flexion (contralateral knee 0-135 degrees). Two
      patients had prominent knots: in one, the knots were painful and were removed
      surgically. Six patients developed patellofemoral chondrosis. Five patients had
      the Mersilene tape tied with the knee in full extension, and all developed
      patellofemoral pain. The other repairs were done with the knee flexed to 90
      degrees before tying; one patient in this group developed patellofemoral
      symptoms. All patients with isolated injuries have returned to employment. There
      were no reruptures or infections.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7623178
TI  - The use of combination internal fixation and hybrid external fixation in severe
      proximal tibia fractures.
AB  - Forty-eight patients with 50 severe fractures of the proximal tibia were followed
      prospectively for 2-4 years (mean 2.7 years) to evaluate the use of limited
      internal fixation combined with external fixation in the treatment of these
      injuries. There were 27 men and 21 women ranging in age from 20 to 74 years.
      Fractures were classified according to the A0 system (Mast J, Ganz R, Jacob R:
      Planning and reduction technique in fracture surgery. Berlin, Springer-Verlag,
      1989), which included 5 A3, 6 C1, 16 C2, and 23 C3 fractures. All patients in
      this series healed; 48 fractures healed in an average of 12 weeks without
      subsequent surgery. There were two (4%) nonunions requiring bone graft. The
      average hospital special surgery knee score was 90 (68-100). Grading criteria for
      anatomical outcome revealed there were 17 (34%) excellent results, 24 (48%) good
      results, 6 (12%) fair results, and 3 (6%) poor results. In conclusion, this
      treatment method is associated with a high percentage of good and excellent
      results. Combined internal and external fixation combines the advantages of
      anatomic, stable fixation with less soft-tissue dissection and eliminates the
      need for large implants.

PMID- 7623179
TI  - Contact characteristics of the subtalar joint after a simulated calcaneus
      fracture.
AB  - A simple calcaneus fracture consisting of two parts was modeled in nine fresh
      cadaver hindfoot specimens to assess changes in subtalar joint contact
      characteristics with increasing plantar depression of the posterolateral fracture
      component. To perform the experiment, rods were placed in the tibial and fibular
      shafts of each specimen, which was mounted in a frame in neutral stance. A
      pneumatic cylinder was used to deliver a vertical compressive load through the
      rods into the foot while permitting free motion of the foot in the horizontal
      plane. Sealed packets of pressure-sensitive film were inserted into the anterior
      middle and posterior facets of the talocalcaneal articulation, and a 700-N load
      was applied. After testing of the intact foot, a primary fracture line was
      created using a microoscillating saw. The osteotomized posterolateral component
      was anatomically reduced and fixed, the film inserted, and the load reapplied.
      The test was repeated after the posterolateral fragment was displaced 2, 5, and
      10 mm in a plantar direction. The resulting pressure prints were scanned along
      with pressure/color density calibration strips using a flat-bed scanner, and an
      image analysis system was used to determine contact areas within specified
      pressure intervals. The contact area (> 0.5 MPa) of the posterior facet was
      significantly decreased with 2, 5, and 10 mm displacements of the posterolateral
      calcaneus fracture component. The ratio of high-pressure area (< 5.0 MPa) to
      contact area in the posterior facet was significantly increased only with
      displacements of 5 and 10 mm. There were no significant changes in any contact
      parameters in the anterior-middle facet.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7623181
TI  - Fracture of a supracondylar humeral myositis ossificans.
AB  - Although myositis ossificans is a well-known sequela of elbow trauma, reinjury to
      the affected region can also occur, resulting in acute symptoms from a fracture
      of the myositis ossificans. An 18-year-old man presented with localized pain,
      soft-tissue swelling, and a bony mass along the anterolateral distal humerus with
      restricted elbow range of motion after injury to his elbow during football. One
      year earlier he had sustained a similar crush injury to his elbow that resulted
      in a limited, although painless, arc of motion. Radiographs and tomograms
      established the diagnosis of a fractured supracondylar humeral myositis
      ossificans. Surgical excision of the large mature ossified fragment confirmed the
      diagnosis and restored a full range of motion of the elbow.

PMID- 7623180
TI  - Chronic fracture-separation of the radial head in a child.
AB  - A rare case of a complete fracture-separation of the proximal radial epiphysis is
      described in a pediatric patient. A further complicating factor is the delay in
      diagnosis that may worsen prognosis. An emphasis on early detection by physical
      examination and imaging studies, as well as consideration of treatment options,
      are presented.

PMID- 7623182
TI  - Retrograde femoral nailing between an ankylosed hip and a stiff knee.
AB  - We describe a case of retrograde nailing of a comminuted infraisthmal femur
      fracture between an ankylosed hip and a stiff knee stemming from heterotopic bone
      and soft-tissue contracture. A tibial nail directed through the medial femoral
      condyle was used. At 1 year follow-up the fracture has united anatomically, and
      the patient has been rehabilitated to his preinjury functional status.

PMID- 7623183
TI  - The importance of liposomes as models and tools in the understanding of
      photosensitization mechanisms.
AB  - The various applications of liposomes in understanding photosensitization are
      described in this paper, with particular emphasis on the various kinds of
      information that these models allow to obtain in phototherapy. Liposomes are
      simple vesicles in which an aqueous phase is enclosed by a phospholipidic
      membrane. They are suitable models mimicking specific situations occurring in
      vivo and they allow study of the influence of physicochemical, photobiological
      and biochemical factors on the uptake of photosensitizers by tissues, their
      mechanisms of action and the subsequent photoinduced tumor necrosis. Moreover,
      solubilization of the sensitizer into the bilayer seems to improve its tumoral
      selectivity and its photodynamic efficiency.

PMID- 7623184
TI  - Non-specific systemic immune suppression induced by photodynamic treatment of
      lymph node cells with bacteriochlorin a.
AB  - Although photodynamic therapy is being used increasingly for the treatment of
      cancer, its effect on immune responses has received little attention. This aspect
      was studied in a rat model. Rats were given (intravenously) lymph node cells
      which were simultaneously exposed to a photosensitizer and light. As a result of
      this treatment the animals showed a decreased contact hypersensitivity response.
      Most important is that the generated immunosuppression proved to be non-specific.
      The consequence of this finding may be that photodynamic therapy of tumours can
      inhibit the immune response against malignant cells.

PMID- 7623185
TI  - Molecular cloning of the human gene SUVCC2 associated with mutagenesis following
      the induction of non-dimer DNA damages by solar UV radiation.
AB  - A mutant cell line, DRP 512, sensitive to the induction of non-dimer DNA damages
      produced by solar UV radiation was derived from ICR 2A frog cells. In addition,
      the DRP 512 cells exhibited an abnormally high level of ouabain-resistant mutants
      after exposure to solar UV. A level of 1.1. mutants per 10(6) survivors per kJ m
      2 was measured for ICR 2A whereas the yield was 4.2 mutants per 10(6) survivors
      per kJ m-2 for the solar-UV-sensitive cell line. The DRP 512 cells were
      transfected with human DNA and a secondary transformant obtained in which normal
      solar UV sensitivity and mutation induction were restored. DNA from this
      secondary transformant was used to construct a genomic DNA library from which a
      recombinant phage was isolated containing the human gene capable of restoring
      normal solar UV sensitivity and mutation induction to DRP 512. This gene has been
      designated SUVCC2.

PMID- 7623186
TI  - Topical application of 5-aminolevulinic acid, DMSO and EDTA: protoporphyrin IX
      accumulation in skin and tumours of mice.
AB  - Topical 5-aminolevulinic acid (ALA) application in three different creams was
      carried out on mice bearing subcutaneously transplanted C26 colon carcinoma. The
      creams contained (a) 20% ALA alone, (b) ALA with 2% dimethylsulphoxide (DMSO) and
      (c) ALA, DMSO and 2% edetic acid disodium salt (EDTA). Protoporphyrin IX (PP)
      production in the tumour and in the skin overlying the tumour was studied by two
      methods: laser-induced fluorescence (LIF) and chemical extraction. The kinetics
      of PP production in the skin and in the tumour, as studied by the LIF method, was
      similar for all three cream preparations. The PP fluorescence intensity in the
      tissues reached its maximum 4-6 h after application of the creams. Quantitative
      analysis showed that the PP concentration after treatment was more pronounced in
      the skin than in the tumour. The efficiency of porphyrin production in the skin
      by the creams used was in the following order: ALA-DMSO-EDTA > ALA-DMSO > ALA. In
      the tumour the enhancing effect of DMSO and EDTA on PP accumulation induced by
      ALA was observed mainly in the upper 2 mm section. However, the concentration of
      PP in the tumour was found to be approximately the same for ALA-DMSO and ALA-DMSO
      EDTA cream combinations. The possible mechanisms of the effect of DMSO and EDTA
      are discussed.

PMID- 7623187
TI  - Modes of photodynamic vs. sonodynamic cytotoxicity.
AB  - We compared effects of ultrasound-induced vs. photodynamic cytotoxicity in cell
      culture. The photodynamic effects mediated by mesoporphyrin caused a delayed
      toxic reaction, the presence of a "shoulder" on the dose-response curve,
      indicating the capacity for limited repair of photodamage. In contrast,
      ultrasound-induced loss of viability resulted from rapid cell destruction and was
      proportional to the time of sonication. Photodynamic damage to cells before
      exposure to ultrasound potentiated cell breakage but did not affect the
      clonogenicity of the surviving cell population. Photodamage after exposure to
      ultrasound decreased the viability of cells which had survived ultrasonic
      treatment.

PMID- 7623188
TI  - Chain elongation of fatty acids in the fish parasite Paratenuisentis ambiguus
      (Acanthocephala).
AB  - An active enzyme system for fatty acid chain elongation exists in Paratenuisentis
      ambiguus (Acanthocephala), which elongates [1-14C]palmitic acid consecutively to
      stearic and arachidic acid. Highest specific activity of radioactive elongation
      products was detected in phosphatidylethanolamines that seem to play an
      outstanding role as acceptors of saturated long-chain and very long-chain fatty
      acids. In contrast, incubation of P. ambiguus with monounsaturated [1-14C]oleic
      acid under similar conditions led to small proportions of labeled eicosenoic acid
      only. Analysis of the fatty acid pattern and stereospecific distribution at the
      glycerol backbone of phospholipids revealed that saturated acyl moieties with 18,
      20, and 22 carbon atoms were esterified almost exclusively in the sn-1 position
      of phosphatidylethanolamines and -cholines, whereas polyunsaturated fatty acids
      were found predominantly in the sn-2 position of these phospholipids. From these
      results it may be concluded that the parasite channels saturated long-chain and
      very long-chain fatty acids predominantly to the sn-1 position of phospholipids
      in order to compensate for increasing membrane fluidity caused by the
      incorporation of high proportions of polyunsaturated fatty acids of aquatic feed.

PMID- 7623189
TI  - Developmentally regulated secretion of cathepsin L-like cysteine proteases by
      Haemonchus contortus.
AB  - Cysteine protease activity was present in media collected after 24 hr in vitro
      culture of adult Haemonchus contortus. The released cysteine protease hydrolyzed
      the fluorogenic 7-amino-4-trifluoromethyl coumarin (AFC)-substituted synthetic
      peptides Z-phe-arg-AFC and Z-ala-arg-arg-AFC, but not Z-arg-arg-AFC or Z-arg-AFC,
      characterizing this activity as cathepsin L-like. Within the parasite, cysteine
      protease activity was highest in extracts of intestinal tissue. Secreted cysteine
      protease inhibited the clotting of sheep blood and hydrolyzed hemoglobin,
      fibrinogen, collagen, and IgG; the IgG hydrolysis site was within the hinge
      region. Four proteases with M(r) values of 30, 34, 37, and 41 kDa were identified
      with biotinylated-phenylalanine-arginine-fluoromethyl ketone, a specific probe
      that binds to active cysteine proteases. Adult parasites cultivated in the
      presence of 0.1 mM levamisole released 50% less protease activity compared to
      control cultures; in the presence of rafoxanide (0.1 mM), protease was not
      detected. Cathepsin L-like cysteine protease activity was released also by L4,
      but not the L3 larval stage. The active and developmentally regulated release of
      cysteine proteases by H. contortus may have a critical function in worm
      nutrition, immune evasion, or both.

PMID- 7623191
TI  - Field studies on the transmission and survival of Cyclocoelum mutabile (Digenea)
      infections in natural snail populations in southern Manitoba, Canada.
AB  - The transmission of Cyclocoelum mutabile to snails was examined under natural
      conditions by sampling the snail communities of 4 natural ponds that had been
      exposed experimentally to infection by laboratory-infected coots (Fulica
      americana). Five of 6 snail species in the ponds, Physa jennessi, Promenetus
      exacuous, Armiger crista, Gyraulus parvus, and Stagnicola elodes, became
      infected. No natural infections were found in the few Helisoma trivolvis
      examined. The second most abundant species Promenetus exacuous was infected most
      often, whereas Physa jennessi, the most abundant species present, was rarely
      infected. The temporal pattern of infections in the snail community suggests the
      transmission window of this parasite in southern Manitoba is limited by both the
      14 C hatching threshold of the fluke eggs and the seasonality of ovigerous
      infections in the coot host. No naturally overwintering infections were found in
      snails from these ponds, which were examined the following spring. None of the
      1,120 laboratory-infected snails placed in cages and held overwinter in the ponds
      survived, whereas 14 of the 1,120 uninfected control snails kept in the same
      cages survived. These results are consistent with the hypothesis that C. mutabile
      must be reestablished in northern waterfowl breeding areas each spring.

PMID- 7623190
TI  - Species- and size-specific infection of snails by Cyclocoelum mutabile (Digenea:
      Cyclocoelidae).
AB  - Infectivity of Cyclocoelum mutabile miracidia to 9 species and up to 4 size
      classes of pulmonate snails at 14, 16, and 20 C was studied under laboratory
      conditions. Of the 9 species examined, 6 (Stagnicola elodes, Lymnaea stagnalis,
      Gyraulus parvus, Gyraulus circumstriatus, Promenetus exacuous, and Armiger
      crista) were highly susceptible (infection success > or = 25%), 2 (Physa jennessi
      and Helisoma trivolvis) had low susceptibility (infection success < 25%, > 0),
      and 1 (Physa gyrina) was not susceptible to infection. Within highly susceptible
      species, snail size was negatively related to susceptibility and temperature had
      variable effects. Infection success was not affected by temperature or snail size
      in species with low susceptibility. Production of cercariae was negatively
      correlated with susceptibility among snails of different sizes and species, but
      was not influenced by snail size for a given species. Among species,
      metacercariae production was typically higher in lymnaeids than in either
      planorbids or physids. Results of experiments where miracidia were provided with
      a choice of 2 different snails suggest that they do not discriminate between
      species with high and low susceptibility.

PMID- 7623192
TI  - Fleas (Siphonaptera) of cotton mice on a Georgia barrier island: a depauperate
      fauna.
AB  - From February 1993 through October 1994, 382 cotton mice Peromyscus gossypinus
      were live-trapped and examined for fleas on St. Catherines Island, Liberty
      County, Georgia. Orchopeas leucopus was the only species of flea collected, with
      an overall prevalence of 27% and a mean intensity of 3.8. This flea was more
      abundant on cotton mice during the cooler months, with peak infestation indices
      recorded in March 1993 and in January 1994. Five species of fleas (Polygenis
      gwyni, Stenoponia americana, Ctenophthalmus pseudagyrtes, Peromyscopsylla scotti,
      and O. leucopus) were collected from 29 cotton mice live-trapped in adjacent
      mainland localities during the same period. The depauperate flea fauna of cotton
      mice on St. Catherines Island suggests that either the original colonizing cotton
      mice were infested by only 1 species of flea (O. leucopus) and that no subsequent
      invasions of cotton mouse fleas have occurred, or that other cotton mouse fleas
      cannot establish on the island.

PMID- 7623193
TI  - Sequence analysis and comparison of ribosomal DNA from bovine Neospora to similar
      coccidial parasites.
AB  - The nuclear small subunit ribosomal RNA (nss-rRNA) gene sequence of Neospora spp.
      isolated from cattle was analyzed and compared to the sequences from several
      closely related cyst-forming coccidial parasites. Double-stranded DNA sequencing
      of 5 bovine Neospora spp. isolates (BPA1-4), 2 Neospora caninum isolates (NC-1
      and NC-3), and 3 Toxoplasma gondii isolates (RH, GT-1, CT-1) were performed and
      compared to each other, as well as to other sequences available in GenBank for
      the NC-1 isolate, Sarcocystis muris, and Cryptosporidium parvum. There were no
      nucleotide differences detected between the Neospora spp. isolates from cattle
      and dogs. Four nucleotide differences were consistently detected when sequences
      of Neospora spp. isolates were compared to those of the T. gondii isolates. These
      results indicate that Neospora spp. and T. gondii are closely related, but
      distinct, species.

PMID- 7623194
TI  - Specific antibody patterns of Wistar rats inoculated with third stage larvae of
      Anisakis simplex.
AB  - Levels of excretory-secretory (ES)-specific antibody were measured in Wistar rats
      inoculated with 1, 5, or 20 third stage larvae (L3) of Anisakis simplex. Primary
      inoculation induced ES-specific IgM and IgG titers, paralleling inoculum size.
      Secondary inoculations resulted in an IgM and IgG titer augmentation in 1 or 5
      larvae-inoculated animals to levels comparable to those of animals inoculated
      with 20 larvae, but titers in high inoculum animals did not increase upon
      secondary inoculation. Primary inoculation induced low ES-specific IgE antibody
      titers. However, secondary inoculation produced a different pattern than with IgM
      or IgG titers. Instead of titers equivalent to animals receiving more larvae,
      rats receiving 1 larva developed higher IgE titers than rats receiving larger
      inoculums. IgE titers of single larvae-inoculated rats peaked at 3-5 days after
      secondary inoculation but disappeared by day 14. The time course of IgE
      production is therefore consistent with duration of the infection. As the natural
      infection typically involves few larvae, monitoring ES-specific IgE may be a
      useful diagnostic tool for human intestinal anisakiasis.

PMID- 7623195
TI  - Repetitive protein antigens of Trypanosoma cruzi have diverse intracellular
      locations.
AB  - We previously identified by immunoscreening Trypanosoma cruzi cDNA libraries a
      group of proteins containing long stretches of tandem repeats. The goal of the
      current project was to gain insight into the functions of these proteins through
      ultrastructural analyses consisting of western blotting and electron microscopic
      localization studies. By comparing western blots of total parasite lysate and
      different fractions of T. cruzi, we found that 3 of the repetitive antigens are
      exclusively associated with the parasite membrane, or cytoskeleton, or both. One
      of the 4 repetitive antigens studied has some association with the membrane or
      cytoskeleton but also appears to be free in the cytosol. In immunoelectron
      microscopic studies, the 4 repetitive antigens were detected in different
      intracellular locations. One of the proteins is located between the flagellum and
      parasite body, the second has a nuclear distribution, the third is associated
      with the cell membrane, and the fourth is dispersed throughout the cytoskeletal
      network. These findings suggest that despite the general structure similarities
      of these repetitive proteins, they may serve different cellular functions.

PMID- 7623196
TI  - The removal of trypanolytic activity from human serum by Trypanosoma brucei
      gambiense and its subsequent recovery in trypanosome lysates.
AB  - Susceptible African trypanosomes are lysed by a factor in human serum (HS), which
      presumably binds to their surface and is then internalized. It has been suggested
      that internalization of the factor is required for lysis. The hypothesis
      predicted that if the trypanolytic factor (TLF) binds and is endocytosed by
      trypanosomes, the lytic activity in HS should be removed by them. The experiments
      in this report have demonstrated that the lytic activity in HS can be almost
      completely removed. This was shown using both human serum sensitive (HSS) and
      resistant clones. As it might have been expected, HSS cells remove a greater
      percentage of the trypanolytic activity. In addition, the hypothesis also
      predicts that if the TLF is processed and activated from inside the trypanosome,
      its activity should be detected in the lysates of thoroughly washed trypanosomes
      previously incubated with HS. The results showed that the lysates consistently
      contained a soluble active form of the TLF that has been internalized by the
      trypanosomes. Antiserum specific to human high-density lipoprotein was found to
      neutralize the trypanolytic activity present in the lysates but failed to prevent
      the lysis of trypanosomes already exposed to HS.

PMID- 7623197
TI  - Antibody production in Syphacia obvelata infected mice.
AB  - Antibody response to Syphacia obvelata infection was observed in AKR/J mice by
      ELISA. Experimental infection with the pinworm eggs showed the presence of
      specific IgG against S. obvelata somatic antigens at 12 days postinfection, and
      that it increased steadily thereafter. Sera of S. obvelata-infected mice showed
      cross-reactivity with somatic antigens of other Syphacia species such as S.
      mesocriceti and S. muris, but not with Aspiculuris asiatica. Western blotting of
      S. obvelata antigen with sera of S. obvelata-infected mice showed a corresponding
      increase in the number of bands during the course of infection. Infected mice
      showed significantly higher antibody production to sheep red blood cells than the
      uninfected control mice. Thus, S. obvelata infection is shown to alter the
      humoral response to nonparasitic antigenic stimuli. These observations indicate
      that infection by helminths, which apparently do not produce clinical symptoms,
      might modulate the immune system of the host and, therefore, affect experimental
      results.

PMID- 7623198
TI  - Development of amebicidal cell-mediated immunity in gerbils (Meriones
      unguiculatus) immunized with the galactose-inhibitable adherence lectin of
      Entamoeba histolytica.
AB  - The galactose-inhibitable adherence lectin of Entamoeba histolytica is a
      protective antigen in the gerbil model of amebic liver abscess. To further
      understand the mechanisms of vaccine efficacy, we studied the cell-mediated
      immune response to the lectin in gerbils. Splenocytes harvested from immunized
      gerbils demonstrated in vitro proliferation and production of interleukin-2 and
      gamma-interferon in response to purified adherence lectin (P < 0.05 for each
      compared to control splenocytes). Splenocytes from immunized gerbils developed
      direct amebicidal activity (P = 0.014) following in vitro stimulation with the
      adherence lectin. Splenocytes harvested from immunized gerbils following
      intrahepatic challenge with viable E. histolytica adherence lectin. Splenocytes
      harvested from immunized gerbils following intrahepatic challenge with viable E.
      histolytica trophozoites demonstrated proliferative and amebicidal responses (P <
      0.05). In conclusion, immunization with the E. histolytica galactose-inhibitable
      adherence lectin elicits an amebicidal cell-mediated response that is enhanced by
      parasite challenge.

PMID- 7623199
TI  - Echinostoma macrorchis: life history, population dynamics of intramolluscan
      stages, and the first and second intermediate hosts.
AB  - Eggs of Echinostoma macrorchis were laid at the 1-cell stage and took 9 days (26
      27 C) or 6 days (30 C) to hatch. The following accounts are based on studies
      undertaken at 24-26 C. Maximum survival of miracidia was 7 hr. Miracidia reached
      the ventricle of Gyraulus chinensis 15-20 hr after penetration and transformed
      into sporocysts. The earliest degeneration of sporocysts occurred 20 days
      postinfection (DPI), but some survived for 120 days. Mature mother rediac were
      first seen inside the sporocyst at 7 DPI, then were released to the ventricular
      cavity and migrated to other anatomical locations of the host. Among the germ
      balls present in a sporocyst, 1-3 developed concurrently to the mother redia
      stage. Young daughter rediae first appeared at 15 DPI and mature ones at 19 DPI.
      Snails of larger size produced more daughter rediae and cercariae than smaller
      ones. Initial shedding of cercariae from infected snails occurred between 25 and
      48 DPI, with a mean of 34 DPI. The cercariae were phototactic and each snail shed
      a daily average of 34 cercariae. Gyraulus chinensis was proven to be the only
      snail capable of serving as the first intermediate host. Tadpoles of Rana
      latouchi and Bufo bufo, 9 species of gastropods, the bivalve Corbicula fluminea,
      and 1 unidentified planarian species served as experimental second intermediate
      hosts.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7623200
TI  - A semiquantitative PCR assay for assessing Perkinsus marinus infections in the
      eastern oyster, Crassostrea virginica.
AB  - A 3.2-kb fragment of Perkinsus marinus DNA was cloned and sequenced. A noncoding
      domain was identified and targeted for the development of a semiquantitative
      polymerase chain reaction (PCR) assay for the presence of P. marinus in eastern
      oyster tissues. The assay involves extracting total DNA from oyster hemolymph and
      using 1 microgram of that DNA as template in a stringent PCR amplification with
      oligonucleotide primers that are specific for the P. marinus 3.2-kb fragment.
      With this assay, we can detect 10 pg of total P. marinus DNA per 1 microgram of
      oyster hemocyte DNA with ethidium bromide (EtBr) staining of agarose gels, 100 fg
      total P. marinus DNA with Southern blot autoradiography, and 10 fg of total P.
      marinus DNA with dot-blot hybridizations. We have used the sensitivity of the PCR
      assay to develop a method for estimating the level of P. marinus DNA in oyster
      hemolymph and have successfully applied this technique to gill tissues. Our
      semiquantitative assay uses a dilution series to essentially titrate the point at
      which a P. marinus DNA target is no longer amplified in a sample. We refer to
      this technique as "dilution endpoint" PCR. Using hemocytes obtained by
      withdrawing a 1-ml sample of hemolymph, this assay provides a nondestructive
      methodology for rapidly screening large numbers of adult oysters for the presence
      and quantification of P. marinus infection levels. This technique is applicable
      to other tissues (gills) and could potentially be applied to DNA extracts of
      whole larvae or spat.

PMID- 7623201
TI  - Investigation of the life cycle and adult morphology of the avian blood fluke
      Austrobilharzia variglandis (Trematoda: Schistosomatidae) from Connecticut.
AB  - This study was undertaken to expand the current knowledge of the life cycle and
      adult morphology of the avian schistosome Austrobilharzia variglandis, which
      causes a marine cercarial dermatitis in New England. The specific objectives were
      to: (1) investigate the seasonality of the infection in the molluscan
      intermediate host, Ilyanassa obsoleta; (2) determine which bird species are
      acting as natural definitive hosts for the parasite; and (3) characterize the
      morphology of the parasite using scanning electron microscopy (SEM). One-thousand
      individuals of I. obsoleta were collected each month for 14 consecutive months
      and examined for the parasite. Ten to 15 specimens of each of the following avian
      species, Larus argentatus, Larus delawarensis, Larus marinus, Phalacrocorax
      auritus, and Branta canadensis, and 2 individuals of Larus atrilla, were
      collected and examined for schistosomes. Twenty adult male and 10 adult female
      specimens of A. variglandis were processed for SEM. Ilyanassa obsoleta was found
      to maintain a relatively low prevalence of infection (0.7-5.1%) throughout the 14
      mo study, but no fully developed cercaria were visible in sporocysts recovered
      from snails collected in winter months. The Larus species had both the highest
      prevalence (85-92.8%) and highest mean intensity (12.1-34.5 male worms) of
      infection with A. variglandis. These data suggest that overwintering snail
      populations can harbor viable infections and in the spring infect shore birds (or
      humans) with cercaria. The snail and definitive host data suggest that A.
      variglandis is a year-round resident of the state.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7623202
TI  - Susceptibility of mule deer (Odocoileus hemionus) and two species of North
      American molluscs to Elaphostrongylus cervi (Nematoda: Metastrongyloidea).
AB  - An experimental study was done to determine whether Elaphostrongylus cervi can be
      transmitted to common intermediate and definitive hosts indigenous to North
      America. First-stage larvae of E. cervi obtained from red deer (Cervus elaphus
      elaphus) in New Zealand developed to the infective third stage in snails
      (Triodopis multilineata) and slugs (Deroceros reticulatum). Two mule deer
      (Odocoileus hemionus) were inoculated orally with 102 or 406 third-stage larvae.
      One animal developed a patent infection on day 121 postinoculation (PI), and the
      other had numerous first-stage larvae in its lungs and colonic feces on 128 days
      PI when it was killed. A control red deer inoculated with 100 larvae began
      passing larvae on 119 days PI. Larval excretion was low and intermittent in the
      mule deer and during the first 4 wk of patency in the red deer. Both mule deer
      developed progressive neurological disease beginning on day 104 PI and had to be
      killed 4 or 7 wk later, respectively. The red deer remained clinically normal.

PMID- 7623205
TI  - Descriptions of two new didymozoids from the barracuda Sphyraena obtusata in
      Kuwait Bay.
AB  - Two new species of didymozoid trematodes, belonging to the subfamily Didymozoinae
      (Ishii, 1935), genus Allodidymozoon Yamaguti, 1959, are described from the
      barracuda Sphyraena obtusata caught in Kuwait Bay. Allodidymozoon pharyngi n. sp.
      from cysts in the pharyngeal muscles is distinguished from its congeners by the
      posteriorly extended testes, glandular cells surrounding the esophagus, and the
      distribution of the ovarian and vitelline branches in the dorsal side of the
      hindbody. Allodidymozoon trilobata n. sp. from cysts in the muscles on the inner
      surface of the operculum is distinguished by the trilobed hindbody and distally
      curved testes.

PMID- 7623203
TI  - Regulatory effect of the level of free Ca2+ of the host cell on the capacity of
      Trypanosoma cruzi to invade and multiply intracellularly.
AB  - We studied whether modification of the free intracellular Ca2+ level of a
      mammalian host cell would affect its susceptibility to infection by Trypanosoma
      cruzi or its capacity to support trypomastigote-->amastigote transformation and
      amastigote replication. Pretreatment of rat heart myoblasts (RHM) with BAPTA.AM
      or Quin-2.AM, intracellular Ca2+ chelators, decreased the susceptibility of these
      cells to infection by untreated trypomastigotes. This was evidenced by a
      significant drop in both the percentage of infected RHM and the average number of
      organisms per 100 host cells relative to control values. Similar RHM treatment
      with the Ca2+ ionophore ionomycin had the opposite effects. The rate of
      trypomastigote-->amastigote transformation measured in RHM that had been treated
      with BAPTA.AM, Quin-2.AM, or ionomycin before and after, but not during co
      culture with trypomastigotes was not significantly altered. The rate of
      intracellular amastigote multiplication measured in RHM exposed to the
      intracellular Ca2+ chelators only after virtually all of the internalized
      trypomastigotes had transformed into amastigotes was significantly decreased by
      incubation with BAPTA.AM or Quin-2.AM but was increased by ionomycin. None of the
      drug treatments affected RHM viability to any significant extent. These results
      suggest that T. cruzi relies on host cell Ca(2+)-dependent events, utilizes host
      cell free Ca2+ during invasion, or both, and highlight a requirement for an
      adequate free Ca2+ level for effective intracellular T. cruzi multiplication but
      not for trypomastigote-->amastigote transformation.

PMID- 7623204
TI  - In vitro characterization of Acanthamoeba castellanii cytopathic effect.
AB  - This study examined the mechanism of the cytopathic effect (CPE) of Acanthamoeba
      castellanii on human target cells. Pathogenic Acanthamoeba trophozoites were
      incubated with human ocular melanoma (OCM1) cells for 30 min, 1 hr, and 3 hr. The
      amoebae were treated with a calcium ionophore (A23187), phorbol myristate ester
      (PMA), calcium channel blocker (Bepridil), cytochalasin D, and L-leucyl-L-leucine
      methyl ester (leu-leu-OMe). Cytolysis was quantified using a spectrophotometric
      assay. Cocultures of amoeba and cells were also observed by transmission electron
      microscopy at 1, 2, and 3 hr. Results show that trophozoites formed pseudopodia
      that made intimate contact with the target cell membrane. Neither amebostomes nor
      phagocytosis was seen. The calcium ionophore A23187 increased the cytopathic
      effect of the trophozoites on the cultured OCM1. In contrast, cytochalasin D,
      Bepridil, and PMA reduced the cytopathic effect. Leu-leu-OMe did not result in
      killing of Acanthamoeba trophozoites. The results suggest that the cytopathic
      effect of Acanthamoeba trophozoites involves calcium channels and cytoskeletal
      elements. There was no evidence of trogocytosis or phagocytosis as sometimes
      occurs in cytolysis by other free-living amoeba. Although Acanthamoeba-mediated
      CPE in some ways resembles CPE produced by cytotoxic lymphocytes, the mechanisms
      are not identical.

PMID- 7623206
TI  - Clemacotyle australis (Monogenea: Monocotylidae) from the white-spotted eagle ray
      Aetobatus narinari (Rajiformes: Myliobatididae) on the Great Barrier Reef:
      redescription, emended generic diagnosis, and oncomiracidium.
AB  - Clemacotyle australis Young, 1967 from the branchial cavity of the type host,
      Aetobatis narinari, is redescribed based on new material from the type locality,
      Heron Island, Queensland, Australia. The generic diagnosis is emended to include
      details of the male copulatory complex. Oncomiracidia, hatched from eggs
      collected from C. australis, are noteworthy in the presence of diffuse pigment
      throughout the body and haptor.

PMID- 7623207
TI  - Cyclic transmission of Sarcocystis gerbilliechis n. sp. by the Arabian saw-scaled
      viper, Echis coloratus, to rodents of the subfamily gerbillinae.
AB  - Infection experiments with rodents and snakes were performed to elucidate the
      life cycle of a Sarcocystis isolate found in an Arabian saw-scaled viper, Echis
      coloratus. Oocytes in feces of the naturally infected and of 2 experimentally
      infected Arabian saw-scaled vipers were already sporulated and contained 2
      sporocysts each, measuring 12.7 (12.3-13.3) microns x 11.0 (10.7-11.4) microns.
      After oral inoculation of various rodent species with these sporocysts,
      sarcocysts developed in the esophagus and skeletal muscles of gerbils and related
      genera. Mature sarcocysts were filiform in shape and reached a maximum length of
      11.7 mm after 5 mo postinoculation (PI), whereas the width did not exceed 190
      microns. The primary cyst wall formed small, knoblike protrusions, which were up
      to 180 nm long and 120 nm wide. Mature schizonts were present in the liver and
      other organs of gerbils between 11 and 14 days PI. After inoculation of vipers of
      3 different genera with mature sarcocysts from gerbils, oocysts developed in the
      intestine of Arabian saw-scaled vipers. A comparison of these data with those
      from previously described Sarcocystis species with snake-rodent life cycles
      suggests that Sarcocystis gerbilliechis is a new species.

PMID- 7623208
TI  - Bilateral, perivulval cuticular pores in trichostrongylid nematodes.
AB  - A new hypodermal gland was discovered in female nematodes of the family
      Trichostrongylidae. Because the new structure appears to be associated with the
      vulva, it was named the perivulval pore. It is similar, based on light and
      scanning electron microscopy, to phasmids that are located laterally on the tails
      of nematodes of the class Secernentea. Like phasmids, perivulval pores are paired
      and bilateral, with cuticular ducts to the surface in the areas of the lateral
      chords. They are located slightly posterior to the vulva in Haemonchus contortus,
      Haemonchus placei, Haemonchus similis, Mecistocirrus digitatus, Mazamastrongylus
      pursglovei, Ostertagia ostertagi, and Cooperia oncophora, but in Trichostrongylus
      colubriformis they are slightly anterior to the vulva. Because of the location
      near the vulva and the similarity in structure to phasmids, which are, at least
      in part, secretory, the perivulval pores should be considered as a possible
      source of a female attractant for males.

PMID- 7623209
TI  - Glucose uptake rates by Schistosoma mansoni, S. haematobium, and S. bovis adults
      using a flow in vitro culture system.
AB  - A simple flow culture apparatus was designed for the short-term in vitro culture
      of adult schistosomes. The use of this system allowed sensitive estimation of
      relative rates of glucose uptake by different species of schistosome. These data
      suggest that in parasites maintained carefully in conditions within the
      physiological range of glucose concentration, uptake of glucose is entirely
      carrier mediated. The rates of glucose uptake by Schistosoma haematobium and its
      close relative Schistosoma bovis were more than twice that recorded for
      Schistosoma mansoni. The relationship between reproductive output, glucose
      requirements, and susceptibility to immune attrition as adults is considered.

PMID- 7623210
TI  - Susceptibility of Guyanan Saimiri monkeys to a chloroquine-sensitive and a
      chloroquine-resistant strain of Plasmodium vivax from Papua New Guinea.
AB  - Attempts were made to infect splenectomized Guyanan Saimiri sciureus monkeys with
      the following Papua New Guinean strains of Plasmodium vivax: AMRU-1, a
      chloroquine-resistant strain; and AMRU-2, a chloroquine-sensitive strain.
      Inoculation of 7 monkeys with the AMRU-1 strain, 4 using blood-stage parasites
      and 3 using sporozoites, all failed to produce infections. Inoculation of 4
      monkeys with the AMRU-2 strain, 3 using blood-stage parasites and 1 using
      sporozoites, were all successful in establishing infections. The results suggest
      that Guyanan Saimiri are refractory to infection with the AMRU-1 strain. If
      refractoriness occurs in other species and subspecies of Saimiri monkeys, then
      studies on the AMRU-1 strain of P. vivax may be restricted to work using Aotus
      monkeys.

PMID- 7623211
TI  - Gastrointestinal helminths from the endangered Hualapai vole, Microtus
      mogollonensis hualpaiensis (Rodentia: Cricetidae).
AB  - The Hualapai vole (Microtus mogollonensis haulpaiensis) is an endangered rodent
      occurring in northwestern Arizona. Helmiths were examined from 47 voles collected
      from 9 localities in northwestern Arizona. A toal of 375 helminths was collected,
      including 2 species of cestodes Anoplocephaloides troeschi and Paranoplocephala
      macrocephala, and 1 cecal nematode Syphacia obvelata. Pinworms were the most
      common helminth, but prevalence and abundance varied among localities. Comparison
      of the pinworms we found with the types of S. obvelata and Syphacia nigeriana
      indicate that those in M. m. hualpaiensis were S. obvelata.

PMID- 7623212
TI  - Absence of protective resistance to homologous challenge infections in jirds with
      chronic, amicrofilaremic infections of Brugia pahangi.
AB  - Most jirds (Meriones unguiculatus) with chronic Brugia pahangi infections remain
      microfilaremic, develop a hyporesponsive state, and are susceptible to
      reinfection. Although few, some jirds become amicrofilaremic or fail to develop a
      microfilaremia. The hypothesis that chronically infected, amicrofilaremic jirds
      may be resistant to reinfection was tested. Twenty-four chronically infected
      amicrofilaremic jirds, with or without circulating antigen, were inoculated
      subcutaneously with 75 B. pahangi third-stage larvae (L3). Necropsies were
      performed 25 days postinoculation, and challenge populations were separated from
      existing worms by size. Similar inoculations and necropsies were performed on
      groups of chronically infected microfilaremic jirds and uninfected jirds. Based
      on worm recoveries, jirds with occult infections were not resistant to
      reinfection. An anamnestic antibody response to extracts of L3 or microfilariae
      (mf) was not seen, nor were antibodies to the surface of L3 or mf. The data
      indicate that a susceptible state is maintained in this model of lymphatic
      filariasis in the absence of circulating mf.

PMID- 7623213
TI  - Prevalence and transmission of cercariae causing schistosome dermatitis in
      Flathead Lake, Montana.
AB  - Numerous studies have been conducted on swimmer's itch, but very few have been in
      Montana and none on Flathead Lake, the largest, natural freshwater lake in the
      western United States. We conducted a study to determine the prevalence of hosts
      transmitting cercariae causing swimmer's itch in this lake. Hosts for this life
      cycle were determined by direct observation of fresh waterfowl fecal material for
      the presence of miracidia, and snails for the presence of cercariae. Swimmer's
      itch-producing cercariae were verified directly by placing various species on the
      arms of human volunteers and waiting for a reaction. Results of the study were
      further substantiated using a controlled experiment in which snails were
      individually infected with miracidia from the suspected waterfowl host and then
      checked for infection after a 6-wk incubation period. Our findings show that the
      common merganser (Mergus merganser) and the snail Stagnicola elrodi were natural
      hosts of the swimmer's itch parasite (Trichobiharzia ocellata) with prevalences
      of 84% and 2.0%, respectively. To our knowledge this is the first documented case
      of S. elrodi transmitting the swimmer's itch cercariae.

PMID- 7623215
TI  - Hymenolepis diminuta metacestodes (Cysticeroids) are unable to utilize exogenous
      trehalose.
AB  - Cysticercoids (metacestodes) of Hymenolepis diminuta were incubated in Tyrode's
      salt solution (pH 7.2) containing 1.25 mM or 40 mM trehalose for 5 or 18 hr, and
      the amounts of trehalose remaining in the media were determined using high
      pressure liquid chromatography. No differences were detected in the amounts of
      trehalose remaining in control (no cysticercoids) or experimental incubations
      under any of the experimental conditions. Thus, cysticercoids are apparently
      unable to utilize trehalose present in the external medium.

PMID- 7623214
TI  - A method for isolation and partial purification of Trichinella spiralis nurse
      cells.
AB  - Invasion of vertebrate muscle cells by larvae of Trichinella spiralis is
      accompanied by redifferentiation of the host myofiber into a novel structure
      called the nurse cell. The nurse cell protects and nurtures the enclosed parasite
      during its long stay in host muscle. It is anatomically independent of the
      surrounding uninfected muscle cells and can be isolated from host tissue by
      mechanical or enzymatic means. Current methods employed for this purpose have
      yielded only small numbers of nurse cells. An apparatus designed to isolate large
      numbers of nurse cells and a method for removal of all free larvae and most host
      muscle debris is described. Homogenization and trypsin digestion of muscle tissue
      was followed by passage of muscle/parasite suspensions maintained at 37 C through
      a jacketed glass column fitted with a 40-mesh stainless steel screen at the top
      and a Nitex screen with 150-microns-diameter pores at the bottom. Nurse cells
      were retained by the Nitex screen. Density gradient centrifugation using Percoll
      removed all free larvae and most contaminating muscle debris from nurse cell
      suspensions. The large quantities of nurse cells made available by this method
      will allow evaluation of the molecular biology, nutrition, biochemistry, and
      metabolism of the enclosed parasite and of the Trichinella-modified host muscle
      cell.

PMID- 7623216
TI  - The inheritance of factors controlling resistance in mice infected with
      Trypanosoma brucei rhodesiense.
AB  - In crosses between 2 recombinant inbred strains of mice (B x H-2 and B x H-14),
      resistance to infection with Trypanosoma brucei rhodesiense as measured by
      survival time is suggested to be controlled by a dominant gene(s). In prior
      studies using the same clone of trypanosomes, but a different set of inbred mouse
      strains, it was demonstrated that resistance in H-2 congenic mice was a recessive
      trait. This work suggests that in mouse trypanosomiasis, the number of genes
      involved in resistance and their dominant or recessive nature will vary between
      different inbred mouse strains. There was a statistically significant difference
      between the survival times of animals with high or low antibody anti-trypanosome
      titers. Differences in survival time were not correlated with the height of the
      first parasitemia. There was, however, a strong negative correlation between the
      number of trypanosomes at the second peak in parasitemia and survival time. It is
      also suggested that the extent to which the host is immunosuppressed early in
      infection determines the ability to control the later peaks in parasitemia, and,
      therefore, survival time.

PMID- 7623217
TI  - Expression of ret proto-oncogene products in the hypoganglionic segment of the
      small intestine of congenital aganglionosis rats.
AB  - The ret proto-oncogene (proto-ret) encodes a receptor tyrosine kinase that
      contains a cadherin-related sequence in the extracellular domain, which plays an
      important role in control of normal cell growth and differentiation. Recent
      studies have shown that familial Hirschsprung's disease is closely linked to the
      proto-ret locus. Immunohistologically studies on congenital aganglionosis rats
      were made using polyclonal antibody generated for the carboxy-terminal sequence
      of the proto-ret products. Immunoreactivity was investigated in the small and
      large intestines of mutant and control rats. It was increased in the ganglia of
      the hypoganglionic segment of the small intestine and was minimal in the
      normoganglionic small intestinal segment of congenital aganglionosis in rats. The
      reactivity was also strong in the ganglia of the large intestine of normal rats.
      Because the proto-ret is preferentially expressed in the neuronal tissue and
      plays a critical role in differentiation of apparently multipotential neural
      crest cells to enteric neurons, the results suggest that abnormal development of
      local vagal neural crest cells, which were influenced by spatially regulating
      factors, results in the hypoganglionic segment.

PMID- 7623218
TI  - Hirschsprung's disease: one surgeon's experience in one institution.
AB  - The clinical experience of 137 patients treated by one pediatric surgeon at
      HanYang University Hospital over 12 years was analyzed. The sex ratio was 3.6:1
      with male predominance. Neonatal Hirschsprung's disease (HD) occurred in 70 cases
      (51.1%). One hundred fourteen cases (83.2%) were short-segment and 23 cases
      (16.8%) were long-segment disease, of which 4 cases were total colon
      aganglionosis. Symptoms were abdominal distension, vomiting, constipation, and
      delayed passage of meconium. Family history was noted in 4 cases: 3 involved
      siblings and 1 involved relatives. All patients were male and had short-segment
      diseases. There were 3 pairs of monozygotic twins discordant for HD. Seventy
      seven two-stage Duhamel operations were performed at the age of 121 +/- 41.3
      days. Primary Duhamel operations were performed on 30 children. Anorectal
      myectomies were performed on 12 cases of short rectal aganglionosis. The
      incidence of enterocolitis was 25.5% preoperatively and 10.1% postoperatively.
      Complications after the Duhamel operation were intestinal obstruction (3), wound
      disruption (4), and septum reformation (3) with fecaloma formation in the blind
      rectal pouch. Bowel function was normalized within 3 months in 77.3% and within 1
      year after operation in 91.6%. Duhamel operation with a GIA stapler after
      preliminary colostomy could be done at the age of 104 days on average with good
      functional results and with acceptable morbidity. Primary Duhamel operation could
      be done safely on the patients whose conditions were diagnosed after 90 days of
      life with good results. There was no mortality after Duhamel operation.

PMID- 7623219
TI  - Rectal irrigations for the prevention of postoperative enterocolitis in
      Hirschsprung's disease.
AB  - The purpose of this clinical trial was to examine the role of rectal irrigations
      in the prevention of postoperative enterocolitis in children with Hirschsprung's
      disease. Over the past 22 years 177 children had surgical treatment for
      Hirschsprung's disease at a single pediatric hospital. Five children have died of
      other causes. Of the remaining 172 patients, follow-up clinical information was
      obtained from 135 (78%). In 1989, all of the children undergoing surgical
      reconstruction for Hirschsprung's disease were placed on routine postoperative
      rectal irrigations with normal saline. The parents were instructed in the
      irrigation technique before leaving the hospital. Irrigations were started 1 to 2
      weeks postoperatively and were performed two times a day for 3 months, then once
      a day for an additional 3 months. There were no complications from the
      irrigations themselves. A previous report from the authors' institution has
      documented five sudden deaths over the past 22 years from fulminant postoperative
      enterocolitis. These five children all had an unremarkable postoperative
      recovery, then developed a rapidly progressive diarrheal illness. All of these
      deaths occurred before the institution of routine postoperative irrigations. Of
      the 135 patients in this review, 40 had the postoperative rectal irrigations. The
      remaining 95 children serve as historical controls. Data analysis showed that 34
      of the 95 children in the nonirrigation cohort developed postoperative
      enterocolitis compared with 3 of 40 in the rectal irrigation cohort; P < .001
      using Fisher's exact test. In the authors' experience, routine postoperative
      rectal irrigations have significantly decreased the incidence and severity of
      enterocolitis in children after surgical correction of Hirschsprung's disease.

PMID- 7623220
TI  - Gastrointestinal function after surgical correction of Hirschsprung's disease:
      long-term follow-up in 135 patients.
AB  - This study is a retrospective review of all children treated for Hirschsprung's
      disease over the past 22 years at a single pediatric institution. During this
      time 177 patients had definitive surgical reconstruction. Five children died of
      causes unrelated to Hirschsprung's disease, and five children died from
      enterocolitis after an uneventful postoperative course. Clinical follow-up
      information was obtained from 135 (78%). Demographic data includes the following:
      sex ratio 74% male, 26% female; current mean age 9.9 years; mean length of follow
      up 7.9 years (range, 3 months to 21.5 years). Mean age at surgical reconstruction
      was 1.6 years. Definitive surgical procedures included endorectal pull-through
      (Soave), 21%; modified Duhamel, 67%; extended side-to-side ileocolic anastomosis,
      8%; rectal myomectomy, 4%. Transition zone was within rectum or rectosigmoid
      region in 86%. Overall, 32% (43/135) report difficulty with fecal soiling, and
      12.6% (17/135) identify this as a severe problem. These numbers include patients
      with trisomy 21 and total colonic aganglionosis. Severe fecal soiling was
      reported in 7.1% (2/28) after an endorectal pull-through, and in 12.1% (11/91)
      after the modified Duhamel. The difference in incidence of soiling after these
      two procedures is not statistically significant. However, 40% (4/10) of the
      patients after the long side-to-side anastomosis for total colonic aganglionosis
      report severe problems with fecal soiling (P = .03). Surgical reconstruction for
      Hirschsprung's disease provides near-normal gastrointestinal function for the
      majority of children, but long-term follow-up shows significant residual problems
      with soiling in 12.6% of the patients. This is consistent with reported
      experience worldwide.

PMID- 7623221
TI  - Predeposited autologous blood transfusion for surgery in infants and children.
AB  - Homologous blood transfusions have associated infectious and immunological risks.
      Since 1989 the authors have conducted predeposited autologous blood transfusions
      (PABT) for infants and children in whom transfusions were expected to be required
      during an elective operation. Autologous blood was deposited in 13 patients
      ranging in age from 9 months to 10 years (median, 21 months) with weight from 7.3
      kg to 33.6 kg (median, 10.5 kg). They included eight patients with Hirschsprung's
      disease, three patients with benign tumors, and two others. The volume of
      predeposition was calculated to maintain the patients' hematocrit at 30% after
      collection. Blood was deposited once or twice, 1 to 2 weeks before the operation.
      The actual volume of predeposited blood was 19.1 +/- 2.4 mL/kg in infants with
      Hirschsprung's disease, 21.8 +/- 10.0 mL/kg in children with Hirschsprung's
      disease, and 12.6 +/- 2.2 mL/kg in children with other diseases. Nine patients
      were operated on using only PABT, 2 patients required homologous blood
      transfusions in addition to PABT, and 2 patients did not require any blood
      transfusions. No complications occurred as a result of PABT except preoperative
      anemia. PABT is a safe and effective means of procuring blood for intraoperative
      transfusions in infants and children undergoing major elective general pediatric
      surgical procedures.

PMID- 7623222
TI  - Amebic hepatic abscess in children.
AB  - The authors retrospectively reviewed all case histories of children with amebic
      hepatic abscess treated from 1975 to 1993 at their hospital. Twenty boys and 12
      girls were diagnosed. Their ages ranged from 10 months to 12 years, with a mode
      of 1 and 2 years. In 17 (53%) of the patients, the abscess remained confined to
      the liver and was treated medically with dehydroemetine and metronidazole.
      Imminence of complication was present in 9 patients (52%), and required
      percutaneous needle aspiration. Imminence of complication was evidenced by: (1)
      clinical worsening of the patient despite adequate medical treatment, (2)
      presence of an abscess of 6 cm or more in a septic patient, or (3) clinical or
      ultrasonographic findings of an abscess on the verge of rupture. All 9 patients
      did satisfactorily. Fifteen cases (47%) were complicated by rupture and required
      surgical treatment. One of these patients died of sepsis. Medical treatment alone
      was excellent for small abscesses. Percutaneous needle aspiration was a
      successful approach in patients with imminence of complication. Surgery was
      reserved for ruptured abscesses.

PMID- 7623223
TI  - Ventral pancreatitis in a patient with pancreas divisum.
AB  - Pancreas divisum results in drainage of most pancreatic secretions through the
      minor papilla via the dorsal duct, and the association of minor papilla stenosis
      has been implicated as a cause of pancreatitis. Most of the reported cases
      represent pancreatitis confined to the dorsal part. The authors treated a 10-year
      old boy with recurrent pancreatitis that was substantially more severe in the
      ventral part. The patient was referred with a brief history of abdominal pain and
      had undergone a laparotomy when segmental ventral pancreatitis had been observed.
      Severe pancreatitis and acute renal failure developed, which required drainage of
      the lesser sac and hemodialysis, respectively. After 5 months, he had another
      episode that subsequently led to a pseudocyst in the ventral part. Endoscopic
      retrograde cholangiopancreatography via minor papilla showed a normal-caliber
      dorsal duct communicating with a part of the fine ventral ducts. A normal biliary
      tree was shown, but no ventral duct was visualized by cannulation to the major
      papilla of Vater. Dual sphincteroplasties and a cholecystectomy were performed.
      The minor papilla was stenotic and admitted only the finest lacrimal duct probe.
      The orifice of the ventral duct could not be observed. Thus it was clarified that
      the dorsal duct with its stenotic orifice had drained both the dorsal and ventral
      pancreas. The patient has remained asymptomatic over 36 months postoperatively.
      Despite their limited experience, the authors believe that (1) this anatomic
      variant led to ventral pancreatitis, and (2) the sphincteroplasty of the minor
      papilla was successful.

PMID- 7623224
TI  - Combined flexible endoscopy and fluoroscopy in the assessment of the gap between
      the two esophageal pouches in esophageal atresia without fistula.
AB  - The authors have used the technique of combined retrograde flexible endoscopy and
      fluoroscopy on two newborn babies with esophageal atresia (EA) without
      tracheoesophageal fistula (TEF). This technique accurately determined the gap
      between the two esophageal ends and predicted the feasibility and timing of
      delayed primary anastomosis. Esophagostomy was not performed, and continuous
      Replogle tube suction of the upper pouch was maintained during the period of
      waiting for 10 and 14 weeks, respectively. Gastrostomy feeding allowed
      satisfactory growth and development during the period of waiting for esophageal
      growth.

PMID- 7623225
TI  - How to avoid complications during percutaneous endoscopic gastrostomy.
AB  - Percutaneous endoscopic gastrostomy (PEG) has advantages over open gastrostomy,
      and is an accepted technique for children. However, a number of technical
      problems may be encountered during insertion. This report identifies those
      problems and proposes precautions that can be taken to reduce their likelihood.
      Recognized major complications include esophageal injury, colonic perforation,
      wound infection, gastric erosion by the gastrostomy tube, and later symptomatic
      gastroesophageal reflux requiring correction by fundoplication.

PMID- 7623226
TI  - Adaptation of an ECMO team in the era of successful alternative therapies for
      neonatal pulmonary failure.
AB  - Neonates with persistent pulmonary hypertension show severe hypoxemia that
      requires a variety of therapeutic modalities. When patients do not respond to
      conventional medical management that includes hyperventilation, inotropic
      support, and vasodilating agents, treatment with extracorporeal membrane
      oxygenation (ECMO) may be used. More recently, high-frequency oscillatory
      ventilation and nitric oxide inhalation have been used in these infants and have
      impacted the need for ECMO. In light of these changes in therapy, the authors
      reviewed the 6-year clinical experience of an ECMO team to assess trends in
      patient population and outcome and document adaptation of the medical
      professionals to a new treatment era. Between 1988 and 1993, 88 neonates who met
      the institutional criteria were placed on venoarterial ECMO. Oscillatory
      ventilation was locally introduced in 1991 and nitric oxide treatment in 1992.
      Patient outcomes for the 1988 to 1990 period were compared with those for 1991 to
      1993. Analyses included indication for ECMO therapy, length and complexity of the
      run, length of hospital stay, and cost of patient care. During the first 3 years,
      65 patients were placed on ECMO, compared with 23 patients during the 3 years
      after introduction of oscillatory ventilation and nitric oxide therapy (P <
      .001). The length of ECMO therapy increased from a mean of 128 hours to 190 hours
      (P = .005), and the average hospital stay, likewise, increased from 27 days to 42
      days. The total cost of care increased by approximately $40,000 per
      patient.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7623227
TI  - Intestinal volvulus: an experience in a developing country.
AB  - Eighty-two children (47 boys and 35 girls) underwent surgery for a variety of
      causes resulting in volvulus. There were 20 neonates, 13 infants, 34 patients
      aged 1 to 5 years, and 15 children above 5 years of age. The majority (88%) of
      the patients were admitted in a state of shock and dehydration. Peritoneal signs
      were present in 74% of the patients. The resection rate was 61%. A high mortality
      rate of 38% was encountered, which was attributed to septicemia, shock, and
      multiorgan failure. The preventive health programs that are being actively
      implemented together with the improvements made in the transport and referral
      systems have fortunately resulted in much-improved survival rates in the recent
      few years.

PMID- 7623228
TI  - Three-dimensional display of the pelvic structure of anorectal malformations
      based on CT and MR images.
AB  - Three-dimensional images of the pelvic structure of patients with anorectal
      malformation (ARM) were constructed by computer graphics based on radiographic
      computerized tomography (CT) and magnetic resonance (MR) images. Organ contour
      data from CT images and raw MR image data were transferred to a personal computer
      and to a graphic workstation respectively. On MR image processing, organs were
      extracted semiautomatically by thresholding enclosed areas. After several steps
      of image processing, three-dimensional anatomy of each anomaly was visualized
      with emphasis on position and shape of the muscle complex. In control patients
      without an anomaly, images showed that the rectum is supported by the levator
      muscle from behind and descends along with the urethra. In the male patient, the
      anal canal separates from the urethra and penetrates through the middle of the
      sphincter complex to reach the orifice. In those with low-type anomaly with a
      fistula opening to the perineum or the vestibule, images showed the fistula
      descending through the anterior portion of the sphincter complex. Images of those
      with a rectourethral fistula could show the muscle complex behind the rectum and
      at the region where the external sphincter should be. In those with cloacal
      anomalies, anatomical position and the shape of three different viscera were
      easily recognized, and the muscle complex was shown like that of rectourethral
      type anomalies. This study is a new approach to the anomaly to facilitate
      understanding it and can assist a surgeon in planning a procedure. This kind of
      application would make it possible for a surgeon to consider the strategy on a
      display screen before the real surgery.

PMID- 7623229
TI  - How important is the role of the internal anal sphincter in fecal continence? An
      experimental study in dogs.
AB  - It is a generalized concept that the internal anal sphincter (IAS) plays a
      significant role in fecal continence by generating high pressure in the anal
      canal at rest and relaxation during rectal distention. Agreement also exists on
      the importance of internal sphincter-saving anoplasty on anorectal malformations
      in establishing anal continence. Twelve dogs were divided into four groups. Group
      1, a control group, was subjected to a perirectal dissection only. Group 2
      underwent the same perirectal dissection plus a 2-cm resection of the anal canal.
      Group 3 underwent the perirectal dissection plus a 4-cm resection of the anal
      canal, and group 4 underwent perirectal dissection and transposition of the anus
      to the posterolateral portion of the voluntary muscle mass. Clinical continence
      was evaluated, and manometric results were compared with preoperative
      measurements. All dogs in groups 1, 2, and 3 were clinically continent without
      soiling except one in group 3, and also manometric results showed minimal change
      between preoperative and postoperative anal pressure profiles. The transposed
      anus of group 4 showed continuous fecal soiling. The anal resting pressure (ARP)
      was also decreased but still existed in this group. This experimental study
      showed that the IAS contributes to the anal resting tone. However, resection of
      the IAS did not completely interfere with fecal continence. The smooth muscle of
      pulled-through rectum seemed to partly take over the function of the IAS.

PMID- 7623230
TI  - Posterior plication of the rectum for rectal prolapse in children.
AB  - Fourteen patients with rectal prolapse (age range, 1 to 12 years) underwent
      posterior plication of the rectum for rectal prolapse. The procedure consisted of
      (1) natal cleft incision, (2) midline separation of the levator muscle, (3)
      dissection of two thirds of the circumference of the rectum, (4) plication of the
      posterior wall of the rectum using U-shaped mattress sutures, and (5) fixation of
      the sutures of the rectal wall to the coccyx. There has been no recurrence of
      prolapse in any of the patients. The authors' experience suggests that an
      elongated rectum is responsible for prolapse. This simple but definitive
      technique is recommended.

PMID- 7623231
TI  - Spiral computed tomography for biliary dilatation.
AB  - Spiral computed tomography (SCT), which consists of rapid volumetric data
      acquisition and planar image display, was performed on 12 patients with biliary
      dilatation after excisional procedure. The technique was evaluated for image
      quality and impact on clinical practice. All patients safely underwent SCT
      scanning after intravenous cholangiography (IVC) without any sedations. In 11 of
      12 patients reliable biliary images were obtained and three-dimensional (3D)
      reconstruction images of the biliary system with bilioenteric anastomosis were
      generally of diagnostic quality even in young children. As a consequence, IVC-SCT
      technique appears to have the potential for improving the efficacy and safety of
      diagnostic CT in investigation of the biliary system. In particular, this
      technique may be useful for detecting bilioenteric anastomotic conditions in
      follow-up studies of pediatric patients with biliary dilatation.

PMID- 7623232
TI  - Antenatal diagnosis of biliary atresia (type I cyst) at 19 weeks' gestation:
      differential diagnosis and etiologic implications.
AB  - At 19 weeks' gestation, two cystic structures were first identified in the
      abdomen of a fetus. A repeat ultrasonography at 34 weeks confirmed a definite
      cyst communicating with the liver. The baby was born at 39 weeks, and serum
      direct bilirubin started to rise to 4.1 mg/dL. An operative cholangiogram at 23
      days of life showed a cystically dilated choledochus with distal atresia and a
      relatively smooth yet hypoplastic intrahepatic biliary tree. Complete
      obliteration of the cystic duct was also noted. After excision of the cystic
      common bile duct, hepatico-jejunal anastomosis was performed, and the patient did
      well for 8 months postoperatively. Liver biopsy showed proliferation of the bile
      ductules, but no interlobular bile ducts were observed in any portal triad. A
      diagnosis of biliary atresia was established. Including the present case, five
      cases of antenatally diagnosed biliary atresia have been reported. All of them
      had type I cyst, and antenatal diagnosis was made at 19 to 32 weeks' gestation.
      Differential diagnosis between biliary atresia of type I cyst and choledochal
      cyst with complete distal obstruction has been a matter of discussion, and
      recognition of the entity of antenatally diagnosed biliary atresia is of
      significant importance from an etiological point of view.

PMID- 7623234
TI  - Liver retransplantation in children.
AB  - Between January 1988 and December 1993, 132 children received 154 orthotopic
      liver transplantation (OLT) at Bicetre Hospital (France). Among them, 18 children
      underwent two and 2 children underwent three transplants (retransplant rate;
      15.2%). Retransplantations were classified into three groups according to the
      interval between both OLTs: 1 (< 7 days, n = 8), 2 (8 days to 6 months, n = 10)
      and 3 (> 6 months, n = 4). Each group was compared with a control group whose
      grafts survived more than 1 week. There were no significant differences regarding
      age (35 +/- 49, 23 +/- 13, and 33 +/- 15 versus 49 +/- 41 months), cold ischemic
      time (566 +/- 105, 470 +/- 144, and 476 +/- 58 versus 455 +/- 110 minutes) and
      reduced size graft ratio (62.5%, 60%, and 75%, versus 58.3%). The causes of graft
      failure included primary nonfunctioning liver (PNF, n = 8) all in group 1 cases,
      biliary complications associated with hepatic artery thrombosis (HAT, n = 10;
      group 2, 6; group 3, 4), chronic rejection (n = 3; group 2, 1; group 3, 2) and
      three others (uncontrollable acute rejection, fulminant hepatitis, and secondary
      dysfunction, all in the group 2). The authors were unable to detect the cause of
      PNF. The overall survival rate after retransplantation was 62.5%, 60.0% and 75%,
      respectively. To reduce the rate of retransplants and improve the prognosis after
      OLT, further investigation into the cause of PNF, refinements in the anastomotic
      technique of the hepatic artery, and also early treatment of HAT are some of the
      goals to be achieved.

PMID- 7623233
TI  - Outcomes of ileocolic conduit for biliary drainage in infants with biliary
      atresia; comparison with Roux-en-Y type reconstruction.
AB  - This study was undertaken to define the role of an ileocolic conduit that was
      devised as anti-reflux procedure in comparative study with Roux-en-Y type
      reconstruction in infants with biliary atresia treated at a single institution.
      The ileocolic conduit (IC) consisted of 30 cm of distal ileum anastomosed to the
      portahepatis and a 10-cm segment of ascending colon vented through the abdominal
      wall, which was later anastomosed to the second portion of the duodenum. In the
      Roux-en-Y type reconstruction (RY), 40 to 60 cm of jejunum was used for the
      hepatic limb. Twenty-three infants in group IC and 16 infants in group RY were
      entered in this study. Mean ages at definitive surgery were 65.3 +/- 23.1 days
      for group IC and 65.0 +/- 19.5 days for group RY. The two groups were compared
      for the postoperative outcomes in terms of bile excretion, incidence of
      cholangitis, esophageal varices, survival rate, and the effects on physical
      development. The follow-up ranged from 4 to 15 years. Bile excretion was obtained
      in all infants in both groups. Twenty infants (87.0%) in group IC and 10 infants
      (62.5%) in group RY became anicteric. Cholangitis occurred in 60.9% of group IC,
      compared with 83.3% for group RY, in which 6 infants required revision to
      complete diversion of Roux-en-Y limb (Suruga II). There was the same occurrence
      rate of esophageal varices for both groups. However, the varices tended to
      develop later in group IC (53.0 +/- 18.4 months) than in group RY (12.7 +/- 6.0
      months) (P < .02).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7623235
TI  - Repair of neonatal aortic coarctation.
AB  - From 1981 to 1991, 146 infants under 1 month of age underwent repair of aortic
      coarctation. Forty-two had isolated coarctation, 53 had associated ventricular
      septal defect, and 51 had complex cardiac defects. The principal mode of
      presentation was congestive heart failure. The mean age at operation was 10.6
      days. The technique for repair was left subclavian artery flap angioplasty in
      126, resection with end-to-end anastomosis in 14, and a variety of repairs in 6
      patients. Concomitant pulmonary artery banding was performed in 62 patients. The
      overall hospital mortality rate was 11%, and there was a strong association with
      pre-existing renal failure. The mean aortic clamp time in survivors was 23.9
      minutes; mean hospital stay was 13.4 days. Significant restenosis occurred in 16
      patients (11%) with an incidence of 10% after subclavian artery flap angioplasty.
      Eleven patients have undergone reoperation, and 5 were managed successfully with
      balloon dilatation.

PMID- 7623236
TI  - Valve replacement for children: report of two cases.
AB  - The authors report on two children who underwent valve replacement. Case 1: A 10
      year-old boy with high fever and severe heart failure was diagnosed as having
      aortic regurgitation and left ventriculo-right atrial fistula caused by active
      infective endocarditis. An aortic annular defect was repaired by a pericardial
      patch to enlarge the aortic annulus followed by aortic valve replacement with a
      17-mm Bjork-Shiley prosthetic valve. He is doing well 2 years after surgery. Case
      2: A 3-year-old girl was diagnosed as having congenital mitral stenosis with
      severe pulmonary hypertension. Mitral valve stenosis was a commissural fusion
      type according to the Carpentier's classification. An open mitral commissurotomy
      was attempted initially, resulting in severe mitral regurgitation. Then, the
      mitral valve was replaced with a 16-mm CarboMedicus bileaflet valve. Her
      postoperative course was uneventful and residual pulmonary hypertension decreased
      gradually. The selection of prosthetic valves is important in its type and size
      in order to obtain as large an orifice as possible. Careful postoperative follow
      up is mandatory.

PMID- 7623238
TI  - Biological characteristics of neuroblastoma with spontaneous tumor reduction: a
      case report.
AB  - The authors examined the biological characteristics of a neuroblastoma with
      spontaneous tumor reduction. A 6-month-old boy with a pelvic neuroblastoma
      underwent surgical extirpation of the tumor 1 month after diagnosis. The size of
      the tumor reduced spontaneously while he was awaiting operation. The low
      proliferative activity of the tumor cells and the presence of apoptosis in the
      tumor tissue were shown by an immunohistochemical method using anti-PCNA antibody
      and a DNA fragmentation analysis, respectively. These results suggest that the
      spontaneous tumor reduction seen in this patient may well be caused by the
      overwhelming apoptosis of tumor cells.

PMID- 7623237
TI  - Neuroblastoma in infants aged less than 6 months: is more aggressive treatment
      necessary? A report from the Pediatric Oncology Study Group of the Kyushu area.
AB  - Infants with neuroblastoma are known to have a better prognosis than older
      children. In Japan in 1985, mass screening for neuroblastoma in infants aged 6
      months was introduced. With this policy, there has been an increase in the number
      of patients seen with neuroblastoma between 6 and 11 months of age. In a previous
      report the authors described the management and prognosis of infants with disease
      detected by mass screening, but there is still little information regarding the
      strategies of management for infants with neuroblastoma aged less than 6 months.
      The authors analyzed the data regarding 27 patients aged less than 6 months
      registered in their region (population 15 million) from 1985 to 1992, and
      compared it with that of the previous 8-year period. In the younger age group,
      there was a significantly higher rate of advanced disease stages (III and IV). In
      spite of the variation in treatment related to the choice of individual
      institutions, infants with stages I, II, and III disease had a good outcome,
      suggesting that aggressive chemotherapy is not necessary unless poor prognostic
      factors are present. One patient with stage IV disease died of disseminated
      disease and one with stage IVs and 22 copies of N-myc oncogene also died of tumor
      relapse in spite of aggressive chemotherapy. It is therefore concluded that the
      prognosis in infants with stage IV and IVs neuroblastoma under the age of 6
      months is not as good as had previously been believed, and that such patients,
      therefore, require special consideration.

PMID- 7623239
TI  - Frantz's tumor (solid and cystic tumor of the pancreas) with liver metastasis:
      successful treatment and long-term follow-up.
AB  - A rare case of Frantz's tumor with liver metastasis is reported. An 11-year-old
      girl had local resection of a Frantz's tumor in the head of the pancreas. Ten
      years later, she had a recurrence in the pancreatic head, and two liver
      metastases were also disclosed at reoperation. Pancreaticoduodenectomy and
      enucleation of metastatic lesions in the liver were performed. Six years after
      the second operation, she is well and free of disease. A review of 174 cases of
      Frantz's tumor disclosed that metastatic disease in the pediatric age group is
      extremely rare and yet the prognosis is favorable. On the other hand, the outcome
      in older patients, especially those over 40 years old, is very poor.

PMID- 7623240
TI  - A new approach to the surgical correction of buried penis.
AB  - Buried penis has been variously attributed to obesity with excessive suprapubic
      fat, severe phimosis with trapping of the penis within the prepubic tissues, and
      inadequate fixation of the penile shaft skin at the base resulting in tenting.
      Previous attempts at surgical correction, by excising suprapubic fat, fixing
      penile shaft skin to the base of the penis, and circumcising, have failed to give
      satisfactory results and, indeed, procedures like circumcision will make the
      condition even worse. The technique developed by the author is based on the
      recognition that this condition exists because of the displacement of the root of
      the penis below its normal position, resulting in the surrounding fat and dartos
      tissues enveloping the penile shaft. In this procedure, dissection at the root of
      the penis is carried out deep down to the corporal bodies. All fibrotic tissue
      that binds the penile shaft is excised. The lengthened penile shaft is anchored
      at its base by suturing the surrounding tissue onto the tunica. This technique
      has been applied in 22 patients ranging in age from 5 months to 11 years. Apart
      from two technical problems, all other patients had satisfactory correction with
      good functional results.

PMID- 7623241
TI  - Characterization of the gubernacular contractile response to calcitonin gene
      related peptide in the mouse.
AB  - Calcitonin gene-related peptide (CGRP) has no effect on quiescent skeletal
      muscle, but cultured neonatal mice gubernacula show rhythmic contractions in
      response to CGRP. This study investigated whether these contractions (1) require
      calcium ions, (2) are activated via acetylcholine receptors, or (3) require
      dihydropyridine receptors. Gubernacula (n = 20 for each experiment) from male
      mice aged 7 days old were preincubated for 30 minutes in aerated culture medium
      (Krebs-Henseleit solution) with (1) up to 1.8 mmol/L of calcium with or without
      CGRP (714 nmol/L), (2) up to 5.0 mumol/L of curare with CGRP and calcium (1.8
      mmol/L), or (3) up to 1 mumol/L of nifedipine with CGRP and calcium. Then they
      were placed on agar-coated grids over the same compound solutions, and observed
      for 2 days by video camera to see contractions. Of gubernacula cultured with
      calcium (1.8 mmol/L) and CGRP, 90% showed contractions, which decreased to 20%
      without CGRP (P < .001) and 15% without calcium (P < .001). Only 5% of
      gubernacula cultured without both CGRP and calcium showed contractions. Also
      these contractions in response to CGRP depended on calcium concentrations in a
      dose-dependent manner. Curare did not suppress contractions. With increasing dose
      of nifedipine, the percentage of gubernacula contracting decreased from 95% to
      0%. These results suggest that developing mouse gubernacular contractions in
      response to CGRP require influx of calcium ions to the sarcoplasm via
      dihydropyridine receptors in a similar manner to contractions of immature cardiac
      or smooth muscles, and these contractions are not activated via acetylcholine
      receptors.

PMID- 7623242
TI  - The effect of the excision of future scrotal skin on testicular descent in
      neonatal rats: a new experimental model of cryptorchidism.
AB  - The ingunoscrotal skin of neonatal rats was widely excised on either the right or
      left side to examine the role of the scrotum in testicular descent. At the age of
      10 days, gubernacular migration was observed to be significantly inhibited on the
      operated side in comparison with that on the nonoperated side. At the age of 60
      to 90 days, 12 of 17 testes on the operated side were located in the superficial
      inguinal position, 2 were in the perineum, and another 3 had descended into the
      contralateral nonoperated scrotum. All the testes descended into the scrotum on
      the nonoperated side and in the normal control rats. Though the histological
      development was remarkably inhibited in the cryptorchid testis, the contralateral
      descended testis did show the same histological appearance as that of the control
      testes in 90-day-old rats. This new model of cryptorchidism is considered to
      provide a simple technique for investigating the mechanism of testicular descent
      and the impaired development of the testes in cryptorchidism.

PMID- 7623243
TI  - Two-layer versus one-layer closure in transverse island flap repair of posterior
      hypospadias.
AB  - Despite its prevalence for more than two decades, one-stage repair of moderately
      severe hypospadias is still associated with a high complication rate. A
      retrospective study of 103 cases of posterior hypospadias treated exclusively
      with the Duckett transverse island flap procedure was conducted to analyze
      factors that might affect the morbidity. The latter included the age of the
      patients, the anatomical variants of the hypospadias, the suture materials and
      the technique used, the length of the urethral tube, and the methods and duration
      of urinary diversion. The fistula rate was 24% (25/103), and the overall
      complication rate was 31% (32/103). The patients in the glanular-subcoronal
      penile variant had a significantly lower overall complication rate than those in
      the penoscrotal-scrotal variant (21% versus 39%, P < .05). The patients with a
      neourethra shorter than 3 cm also had significantly less complications than those
      with a neourethra longer than 3 cm (25% versus 47%, P < .05). The only procedural
      factor that makes a difference is the method of skin closure to form the
      neourethra. Two-layer closure resulted in a significantly lower fistula rate and
      overall complication rate than one-layer closure (13% versus 34% and 15% versus
      45%, P < .025 and P < .005, respectively). The study confirms the value of two
      layer closure in the transverse island flap repair of posterior hypospadias.

PMID- 7623244
TI  - Nitric oxide reversal of recurrent pulmonary hypertension and respiratory failure
      in an infant with CDH after successful ECMO therapy.
AB  - Nitric oxide (NO) represents a new therapeutic modality for treating neonatal
      pulmonary hypertension and may obviate the need for extracorporeal membrane
      oxygenation (ECMO) in a number of cases of neonatal respiratory failure.
      Recently, the authors treated an infant with a congenital diaphragmatic hernia
      and pulmonary hypertension with NO on two separate occassions. During the initial
      period of stabilization, NO failed to reverse the pulmonary hypertension and
      prevent the development of progressive respiratory failure. After a successful
      course of ECMO, recurrent pulmonary hypertension developed that was successfully
      treated with continuous low-dose NO therapy for over 1 month. Prolonged
      administration of NO in varying doses titrated to clinical and echocardiographic
      parameters was well tolerated by the infant and prevented the need for a second
      run of ECMO.

PMID- 7623246
TI  - Latex anaphylaxis: report of occurrence in two pediatric surgical patients and
      review of the literature.
AB  - This report describes two cases of intraoperative anaphylaxis in children
      sensitized to latex. Both children were undergoing nonurological procedures and,
      despite numerous previous operations, neither had a history of unusual reaction
      or anaphylaxis during surgery. The problem of latex allergy is discussed with
      review of the current literature and suggestions for management.

PMID- 7623245
TI  - Castleman's disease presenting as a pediatric surgical problem.
AB  - A 9-year-old girl presented with anemia, fever, and poor growth over a 2 1/2-year
      period. On physical examination, a right lower quadrant mass was palpated. Her
      signs and symptoms were consistent with Castleman's disease of the plasma cell
      type. The mass, a giant hyperplastic lymph node, was excised, and the patient's
      symptoms resolved. Castleman's disease is a benign lymph node disorder that
      occurs very rarely in the pediatric population and is cured by operative excision
      of the lymphatic mass.

PMID- 7623247
TI  - Luminal narrowing after autoanastomosis and intraluminal slough in
      intussusception: a case report and historical review.
AB  - Historical literature notes slough of an intussusceptum with autoanastomosis as
      an infrequent natural course of childhood intussusception resulting in survival.
      The case of an 8-year-old boy with abdominal pain several years after an apparent
      untreated childhood intussusception is presented. Cecal resection shows evidence
      of previously sloughed intussusceptum with cicatral luminal narrowing at site of
      autoanastomosis. This case illustrates a rare cause of abdominal pain and partial
      intestinal obstruction in childhood.

PMID- 7623248
TI  - Management of intussusception.

PMID- 7623249
TI  - Effects of tetracycline HCl conditioning and fibrin-fibronectin system
      application in the treatment of buccal gingival recession with guided tissue
      regeneration.
AB  - A split-mouth clinical trial was designed to evaluate the effect of treating deep
      wide buccal gingival recession with guided tissue regeneration using expanded
      polytetrafluoroethylene membrane combined with tetracycline HCl (TTC) root
      conditioning and fibrin-fibronectin sealing system (FFSS) application. Eight
      patients, aged 25 to 57 years, each presenting two similar mucogingival defects,
      were selected. The two bilateral recessions were randomly assigned in each
      patient to either test or control treatment procedure. After initial therapy,
      each patient was examined for assessment of plaque, gingivitis, recession depth
      (RD), probing depth (PD), probing attachment level (PAL), and keratinized tissue
      width (KT). The test procedure included the elevation of mucoperiosteal flap at
      the buccal aspect of the alveolar process. The root was debrided and
      demineralized with 100 mg/ml TTC solution for 4 minutes using a burnishing
      technique with cotton pellets. A teflon membrane was secured and a film of FFSS
      was applied between the membrane and the root surface. The buccal flap was
      sutured to completely submerge the membrane. Control treatment included gingival
      flap surgery with barrier membrane alone. After 6 weeks, the membrane was
      removed. Healing was evaluated 6 months after surgery. Both test and control
      procedures resulted in highly significant recession reduction (3.0 mm +/- 1.1 and
      2.6 mm +/- 1.2, respectively) and attachment gain (3.6 mm +/- 1.7 and 2.6 mm +/-
      1.1, respectively). Mean root coverage was of 67% in the TTC + FFSS treated sites
      and 60% in membrane-only treated sites. However, only treatment with TTC + FFSS
      significantly reduced PD and increased KT (P < 0.05). When treatments were
      compared, changes in PD and PAL were significantly greater in TTC + FFSS treated
      sites (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7623250
TI  - Longitudinal assessment of early onset periodontitis.
AB  - The purpose of this study was to determine the clinical course of early onset
      periodontitis and to investigate factors which may influence its clinical course.
      For the past 15 years we have been conducting a study of families with early
      onset periodontitis, and have examined 142 localized juvenile periodontitis and
      185 severe generalized early onset periodontitis patients. In order to study the
      clinical course of early onset periodontitis we recalled our subject population
      to determine their periodontal status. Forty (40) patients with localized early
      onset periodontitis (LJP) and 48 with generalized early onset periodontitis (SP)
      were re-examined. The time since the most recent visit for LJP patients was
      approximately 3 years and for SP patients almost 4 years. LJP patients who
      received periodontal therapy on the average gained periodontal attachment. In
      contrast, LJP patients who did not receive therapy lost periodontal attachment.
      SP patients lost periodontal attachment regardless of whether or not they had
      periodontal therapy. SP patients also lost an average of one tooth during the
      approximately 4 years of observation. LJP patients lost very few teeth with only
      4 teeth being lost in 40 patients. The results of this study suggest that
      localized juvenile periodontitis is a stable disease in most individuals. In
      contrast, patients with severe generalized early onset periodontitis continued to
      lose both periodontal attachment and teeth.

PMID- 7623251
TI  - A comparison of topical ketorolac, systemic flurbiprofen, and placebo for the
      inhibition of bone loss in adult periodontitis.
AB  - Systemic non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to reduce
      alveolar bone loss in periodontitis. This study assesses the efficacy of a
      topical NSAID rinse, containing ketorolac tromethamine as the active agent. Adult
      periodontitis patients (n = 55) were studied in this 6-month randomized, double
      blind, parallel, placebo and positive-controlled study. Each patient had a least
      3 sites at high risk for bone loss as assessed by low dose bone scan. Groups,
      balanced for gender, were assigned to one of three regimens: bid ketorolac rinse
      (0.1%) with placebo capsule; 50 mg bid flurbiprofen capsule (positive control)
      with placebo rinse; or bid placebo rinse and capsule. Prophylaxes were provided
      every 3 months. Monthly examinations assessed safety, gingival condition, and
      gingival crevicular fluid PGE2. Standardized radiographs were taken at baseline
      and at 3 and 6 months for digital subtraction radiography. A significant loss in
      bone height was observed during the study period in the placebo group (-0.63 +/-
      0.11; P < 0.001), but not in the flurbiprofen (-0.10 +/- 0.12; P = 0.40) or
      ketorolac rinse (+0.20 +/- 0.11 mm; P = 0.07) groups. Nested ANOVA revealed that
      ketorolac and flurbiprofen groups had less bone loss (P < 0.01) and reduced
      gingival crevicular fluid PGE2 levels (P < 0.03) compared to placebo. ANOVA
      suggests (P = 0.06) that ketorolac rinse preserved more alveolar bone than
      systemic flurbiprofen at the dose regimens utilized. These data indicate that
      ketorolac rinse may be beneficial in the treatment of adult periodontitis.

PMID- 7623252
TI  - The effects of culture environment on the response of human gingival fibroblasts
      to cyclosporin A.
AB  - In contrast to monolayer cell culture, the use of a 3-dimensional culture system
      creates an environment which is more physiologically comparable to conditions in
      vivo. This study aimed to investigate the effects of culture environment on
      growth and protein biosynthesis by 6 human gingival fibroblast cell lines exposed
      to cyclosporin A (CsA). Fibroblasts were grown both in monolayer culture on
      plastic and embedded within collagen gel. Cyclosporin A was added to cultures at
      a range of concentrations between 10(-5) and 10(-9) g/ml. Under both culture
      conditions CsA had little effect on cell growth at low concentrations but at the
      highest concentration of 10(-5) g/ml, there was a significant inhibitory effect
      on growth (P < 0.05). Protein production was not significantly affected by CsA in
      either culture system. Total collagen production appeared to be inhibited at high
      concentrations of CsA when cells were grown on plastic but remained unaffected
      when the cells were grown in collagen gel. Total protein and collagen production
      per cell in collagen gel was substantially greater compared with cells grown on
      plastic. We conclude that under the conditions of this investigation CsA did not
      directly stimulate growth or matrix-synthesis by normal human gingival
      fibroblasts cultured in 3-dimensional collagen gel or as monolayers on plastic.

PMID- 7623253
TI  - Factors influencing nifedipine-induced gingival overgrowth in rats.
AB  - Factors such as age, the dose of nifedipine administered in the diet, serum drug
      level, duration of drug administration, and sex which may influence nifedipine
      induced gingival overgrowth were examined in a rat model using 20-, 50-, and 90
      days-old male and female rats. Oral administration of nifedipine (50 to 250 mg/kg
      diet) increased the serum level of the drug in a dose-dependent manner in both
      males and females. However, a higher serum level was required in females than
      males to attain the same degree of gingival overgrowth. The minimum dietary
      concentrations of the drug required to elicit gingival overgrowth in males and
      females were 150 and 100 mg/kg, respectively, which gave respective minimum serum
      levels of 800 and 1100 ng/ml. The degree of overgrowth depended on the serum
      concentration of the drug after it had reached the required minimum in male and
      female animals. Administration of nifedipine (250 mg/kg diet) for 20 days was
      enough to induce maximal overgrowth, but this induction occurred only in rats
      that started to receive the drug when they were 20 days old, not in those that
      started at 50 and 90 days of age for the same administration period of 55 days,
      and the overgrowth regressed and the gingiva were normal 40 days after ceasing
      drug administration. These results suggest that gingival overgrowth occurred in
      accordance with the drug concentration in the diet, as well as that in the serum,
      and was more likely to occur in males and younger individuals.

PMID- 7623254
TI  - Protective immunity to Porphyromonas gingivalis infection in a murine model.
AB  - The mouse abscess model has been used extensively to demonstrate protection after
      challenge with periodontopathic organisms. In the present study, an outer
      membrane (OM) preparation of P. gingivalis ATCC 33277 was used to immunize BALB/c
      mice prior to challenge with live P. gingivalis organisms. This OM preparation,
      particularly at the highest dose level of 100 micrograms/immunization, was able
      to induce high levels of specific antibody and subsequent protective immunity.
      Protection in all immunized mice was noted by the rapid healing of the primary
      lesions, a low incidence of secondary lesions, and, in the highest dose group, an
      absence of septicemia. Non-immunized animals demonstrated a slower development as
      well as healing of primary lesions, with higher numbers and larger sizes of
      secondary lesions. Weight loss and behavior patterns such as hunched bodies,
      ruffled hair, and stiffness of the hind legs were particularly noted in this
      group. Depletion of CD4 T cells in mice prior to immunization with 100 micrograms
      P. gingivalis OM resulted in significantly depressed serum levels of anti-P.
      gingivalis antibody and an increase in the physical signs of disease compared
      with both the immunized and control groups. Western blot analysis demonstrated
      three antigen bands (63.3, 50.1, and 45.1) recognized by all immunized groups and
      also the control non-immunized group, although the latter recognition occurred
      only after challenge. A further antigen band of 36.1 kDa was recognized by sera
      from the highest dose group only. This study has demonstrated the ability of P.
      gingivalis OM to provide protection against challenge with live P. gingivalis
      organisms. The increased physical signs of disease seen in the CD4 depleted
      animals compared with the control group not only illustrate the protective role
      of serum antibody, but also suggest a possible role for T cell mechanisms in
      control of the lesion locally. The ability of specific OM antigens to provide
      similar protective immunity remains to be ascertained.

PMID- 7623255
TI  - IgG antibody subclass response to Porphyromonas gingivalis outer membrane
      antigens in gingivitis and adult periodontitis.
AB  - Porphyromonas gingivalis is an important oral pathogen with a strong association
      with adult periodontitis. Significant titers of specific IgG antibodies to P.
      gingivalis can be found in the sera of both gingivitis and periodontitis
      patients. Since IgG subclasses have different biological characteristics, the
      present study dealt with the serum IgG subclass response to outer membrane
      antigens of P. gingivalis. Western blot analysis of P. gingivalis outer membrane
      was carried out using 20 adult periodontitis and 20 age- and sex-matched
      gingivitis patients. Antibodies in sera of both adult periodontitis and
      gingivitis patients recognized 38 antigen bands, ranging in molecular mass from
      11.1 to 161 kDa. IgG2 was the predominant antibody subclass response in both
      patient groups in terms of the numbers of outer membrane antigens recognized,
      followed by IgG3, IgG1, and IgG4. More antigens in all IgG subclasses except IgG4
      were recognized in adult periodontitis cases. Of the 23 antigens identified by
      IgG2 antibodies, 9 were recognized predominantly in adult periodontitis and 3 in
      the gingivitis group. In the IgG1 subclass, 4 antigens were recognized
      predominantly in the adult periodontitis group while only 1 antigen was
      recognized significantly more in the gingivitis group. The IgG3 response
      identified 14 antigens ranging in molecular mass from 11.1 to 61.2 kDa in both
      groups. Ten antigens were recognized significantly by the adult periodontitis
      group. The lowest response was seen by IgG4 antibodies, with only 3 antigens of
      molecular mass 61.2, 52.3, and 38.8 kDa recognized, the latter two significantly
      in the adult periodontitis group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7623256
TI  - Serum antibodies to Porphyromonas gingivalis in children.
AB  - Serum samples from 41 periodontally healthy children aged 1 to 16 years were
      examined by ELISA for the presence of antibodies against a glass bead-EDTA cell
      surface extract (GBE) and LPS of Porphyromonas gingivalis strain ATCC 33277. P.
      gingivalis was detected by immunofluorescence, using a species-specific
      monoclonal antibody, in 41% (17/41) of the children, and isolated from a single
      subject (2.4%). IgM, IgG, and IgA against GBE were detected in respectively 39/41
      (95%), 41/41 (100%), and 27/41 (66%) of the sera. In 22/39 sera, the IgG titer
      was below 50% that of a reference pool of adult sera (RP). In 13/41, the IgM
      titer was higher than that of the RP, mostly in the deciduous dentition group.
      Detectable IgA titers were always below 67% that of the RP. A polarized
      distribution of the children appeared, separating 21 non- and low IgA responders
      (IgA titer below 10% that of the RP) from the remaining 20 subjects. Anti-LPS
      IgG, IgM, and IgA were detected in 41/41 (100%), 39/41 (95%), and 23/38 (61%)
      respectively of the children. In 32/41 sera, the anti-LPS IgG titer was below 50%
      that of the RP, while in 20/39 sera, IgM titers were higher. A clearcut dichotomy
      in IgA response was observed, allowing us to distinguish non-IgA responders (39%)
      and IgA responders to LPS (61%). Our results indicate that serum antibodies to P.
      gingivalis are highly prevalent in children, suggesting that an active primary
      immune response and a secondary immune response are well underway.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7623257
TI  - Guided tissue regeneration in human furcation defects after using a biodegradable
      barrier: a multi-center feasibility study.
AB  - This multi-center study evaluated guided tissue regeneration (GTR) in Class II
      furcation defects using a polylactic acid biodegradable barrier in 29 patients
      with mandibular and maxillary molar defects. Following an initial hygienic phase,
      surgical flaps were elevated, and the sites scaled and root planed. Furcation
      defect perimeter was measured and a customized barrier (thickness 600 to 750 mu)
      was applied to cover the defect. Barriers adhered directly to tooth and bone. At
      baseline, sites were measured for probing depth (PD) (6.0 +/- 0.2 [SE] mm),
      gingival margin location (GML) (-0.2 +/- 0.2 mm), and attachment level in both
      vertical (AL-V) (6.2 +/- 0.2 mm) and horizontal (AL-H) (5.4 +/- 0.2 mm)
      directions. After the surgical procedure, there was good compatibility between
      the gingival tissues and barrier material. Clinically, barriers fragmented and
      became displaced in 3 to 6 weeks. Substantial granulation tissue was sometimes
      present between barrier and root surfaces. Comprehensive periodontal examination
      parameters were measured 3, 4, 6, 9, and 12 months after baseline. A repeated
      measures ANOVA was used to evaluate changes from baseline. At 6 and 12 months
      postsurgery, GML was close to the presurgical level (-0.5 +/- 0.2 mm). There was
      clinically and statistically significant improvement in all other parameters:
      mean PD reduction (2.2 mm), AL-V gain (1.7 mm), and AL-H gain (2.5 mm). These
      results indicated favorable clinical regenerative outcomes after using this
      barrier material in Class II furcation defects in humans.

PMID- 7623258
TI  - Periodontal microbiota of mobile and non-mobile teeth.
AB  - The mechanism of accelerated periodontal destruction around teeth with occlusal
      trauma and increased mobility remains unclear. One possibility is that tooth
      mobility creates a subgingival environment conducive to overgrowth by periodontal
      pathogens. This study compared the subgingival microflora in mobile and non
      mobile teeth of 35 adults on supportive maintenance therapy and 15 with untreated
      adult periodontitis. In each subject, subgingival paper-point samples were
      obtained from a mobile tooth with a probing depth of 4 mm or greater and from a
      non-mobile tooth with similar probing depth and gingival index. Samples were
      transported in VMGA III medium. Pockets around mobile teeth harbored
      significantly higher proportions of Campylobacter rectus (P = 0.001) and
      Peptostreptococcus micros (P = 0.05) than pockets with non-mobile teeth. Mobile
      teeth also tended to show elevated levels of Porphyromonas gingivalis, but this
      did not reach statistical significance. This study suggests that tooth mobility
      may constitute a risk for periodontal breakdown due to an increased subgingival
      occurrence of specific periodontopathogens. This hypothesis needs to be verified
      in longitudinal clinical and microbiological studies.

PMID- 7623259
TI  - Studies on the phenotypic and functional characterization of peripheral blood
      lymphocytes from patients with early-onset periodontitis.
AB  - Juvenile and rapidly progressive periodontitis are grouped under the heading of
      patients with early-onset periodontitis (EOP). Many studies have investigated
      host risk factors in the etiology of EOP patients but these remain inconclusive.
      This study was undertaken to assess the possibility that an abnormality in the
      systemic lymphocyte subpopulation or function is involved in the etiology of EOP
      patients. Fourteen (14) patients with juvenile periodontitis (JP), 18 with
      rapidly progressive periodontitis (RPP), 22 with adult periodontitis (AP), and 33
      with a healthy periodontium (HP) participated in this study. Lymphocyte subsets
      were determined by using panels of monoclonal antibodies (mAbs) and fluorescent
      flow cytometry. T cell blastogenesis was evaluated by [3H]-thymidine uptake.
      Pokeweed mitogen induced immunoglobulin G (IgG) and IgM synthesis were detected
      by sandwich enzyme-linked immunosorbent assay. There were wide distributions of
      values in all examinations among subjects. No significant difference could be
      found between the periodontitis patients and HP groups with the exception of a
      high CD4/CD8 ratio in all patient groups (P < 0.0001) and the depressed
      percentages of CD3 positive cells noted in the AP patient group (P < 0.0001).
      These results suggest that the majority of EOP patients do not show significantly
      different lymphocyte profiles from AP patients and HP subjects, and that
      lymphocyte cell dysfunctions are not always seen, even in EOP patients.

PMID- 7623260
TI  - Gingiva thickness in guided tissue regeneration and associated recession at
      facial furcation defects.
AB  - Consistently successful regenerative therapy for furcation defects using membrane
      techniques remains a challenge for clinicians. The purpose of this study was to
      determine if the thickness of tissue used to cover the membrane influences
      postsurgery recession. Thirty-seven (37) moderate to advanced adult periodontitis
      patients presenting with at least one mandibular or maxillary molar class 1 or 2
      facial furcation involvement participated in the study. Mid-facial presurgery
      recession was recorded from the cemento-enamel junction to the free gingival
      margin at a reproducible point. Mid-facial tissue thickness was measured using
      calipers at a point 5 mm apical to the gingival margin of the mucogingival flap
      reflected at the time of guided tissue regeneration surgery. Patients were
      divided into 2 groups based upon tissue thickness measurement. Patients were then
      re-evaluated for recession at 6 months postsurgery. Sixteen (16) patients with
      tissue thickness < or = 1 mm demonstrated a mean 2.1 mm increase in recession,
      while 21 patients with tissue thickness > 1 mm exhibited a mean 0.6 mm increase
      in recession. We conclude that there is less post-treatment recession (P < 0.01)
      for tissue thickness > 1 mm than tissue thickness < or = 1 mm. Hence, thickness
      of gingival tissue covering a membrane appears to be a factor to consider if post
      treatment recession is to be minimized or avoided.

PMID- 7623261
TI  - Clinical and laboratory studies on a patient with early onset periodontitis and
      her family members. A case report.
AB  - Extensive clinical, microbiological, hematological, and immunological studies
      were performed on a patient with early onset periodontitis (EOP) and two other
      members of the family. The proband, a 27-year-old female, had early onset
      periodontitis and a high level of serum rheumatoid factors (RF) with no
      diagnosable medical disease. Her mother had lost all her teeth at the age of 50
      because of advanced periodontitis, while her elder sister was unaffected by
      periodontitis. Neither the proband's periodontally-affected mother nor her
      unaffected sister exhibited a detectable level of RF. In this study, we examined:
      1) serum immunoglobulin G (IgG) antibody titers against putative periodontal
      pathogenic bacteria; 2) peripheral neutrophil functions; 3) phenotypic analyses
      of peripheral lymphocyte subpopulations; and 4) peripheral lymphocyte functions
      (T cell proliferative activity, ability of cytokine [interleukin (IL)-2, tumor
      necrosis factor-alpha, interferon-gamma, IL-6 and IL-8] and IgG and IgM
      productivity). High antibody titers to Actinobacillus actinomycetemcomitans,
      Porphyromonas gingivalis, and Campylobacter rectus were detected in the sera of
      the proband, as were high serum antibody titers to P. gingivalis in the mother
      and to C. rectus in the unaffected sister compared to the non-periodontitis
      affected subjects. The proband also showed enhanced neutrophil chemotaxis; a high
      percentage of pan-B cells; and high productivity of IL-6, IgG, and IgM compared
      to individuals who were not periodontally affected. The mother showed slightly
      low helper/induced T cells (Th/i) suppressor/cytotoxic T cells (Ts/c) ratios due
      to the elevated count of Ts/c, and high IFN-gamma productivity compared to
      control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7623262
TI  - Papillon-Lefevre syndrome: a review of the literature and report of 4 cases.
AB  - This report describes 4 cases of Papillon-Lefevre syndrome (PLS) affecting 2
      Jordanian families with a total of 8 children. In family A, 3 girls out of 6
      siblings were affected; and in family B, the eldest of 2 brothers. The patients
      were between 4 1/2 and 12 years old, and their parents, who are first cousins,
      were not affected. Diagnosis was determined by history, and clinical, laboratory,
      and radiographic examinations. All present cases exhibited the typical clinical
      features of PLS: hyperkeratosis of the palms and soles and the presence of
      advanced destructive periodontitis resulting in early loss of both the primary
      and permanent dentitions. In Case 4, cutaneous lesions were noticed at age 6
      months and the child was edentulous by the age of 12 years. In all cases, there
      was a relationship between increased severity of skin lesions and seasonal
      variations and intensified periodontal destruction. There was an early eruption
      of the permanent teeth. The teeth were caries-free with no sign of root
      resorption. Dentists play a significant role in the diagnosis and management of
      PLS patients.

PMID- 7623263
TI  - Spiritual care: reflecting God's love to children.

PMID- 7623264
TI  - My son, Dan: a mother's insights into caring for an autistic child.

PMID- 7623265
TI  - When a child grieves: lessons in a tree house.

PMID- 7623266
TI  - Joy comes in the morning: a newborn fights for life.

PMID- 7623267
TI  - Emergency baptism.

PMID- 7623268
TI  - Somebody's son: a patient only a mother could love.

PMID- 7623269
TI  - Welcoming children.

PMID- 7623270
TI  - Rwandan relief: when God called me back.

PMID- 7623271
TI  - All God's Annies: the kids who don't grow up.

PMID- 7623272
TI  - Why did God put me here?

PMID- 7623273
TI  - Ages & stages of spiritual development.

PMID- 7623274
TI  - Intracellular calcium and its sodium-independent regulation in voltage-clamped
      snail neurones.
AB  - 1. We have used both Ca(2+)-sensitive microelectrodes and fura-2 to measure the
      intracellular free calcium ion concentration ([Ca2+]i or its negative log, pCai)
      of snail neurones voltage clamped to -50 or -60 mV. Using Ca(2+)-sensitive
      microelectrodes, [Ca2+]i was found to be approximately 174 nM and pCai, 6.76 +/-
      0.09 (mean +/- S.E.M.; n = 11); using fura-2, [Ca2+]i was approximately 40 nM and
      pCai, 7.44 +/- 0.06 (mean +/- S.E.M., n = 10). 2. Depolarizations (1-20 s) caused
      an increase in [Ca2+]i which was abolished by removal of extracellular Ca2+,
      indicating that the rise in [Ca2+]i was due to Ca2+ influx through voltage
      activated Ca2+ channels. 3. Caffeine (10-20 mM) caused an increase in [Ca2+]i in
      the presence or absence of extracellular Ca2+. The effects of caffeine on [Ca2+]i
      could be prevented by ryanodine. 4. Thapsigargin, an inhibitor of the endoplasmic
      reticulum Ca(2+)-ATPase, caused a small increase in resting [Ca2+]i and slowed
      the rate of recovery from Ca2+ loads following 20 s depolarizations. 5. Neither
      replacement of extracellular sodium with N-methyl-D-glucamine (NMDG), nor loading
      the cells with intracellular sodium, had any effect on resting [Ca2+]i or the
      rate of recovery of [Ca2+]i following depolarizations. 6. The mitochondrial
      uncoupling agent carbonyl cyanide m-chlorophenylhydrazone (CCmP) caused a small
      gradual rise in resting [Ca2+]i. Removal of extracellular sodium during exposure
      to CCmP had no further effect on [Ca2+]i. 7. Intracellular orthovanadate caused
      an increase in resting [Ca2+]i and prevented the full recovery of [Ca2+]i
      following small Ca2+ loads, but removal of extracellular sodium did not cause a
      rise in [Ca2+]i. We conclude that there is no Na(+)-Ca2+ exchanger present in the
      cell body of these neurones and that [Ca2+]i is maintained by an ATP-dependent
      Ca2+ pump.

PMID- 7623275
TI  - Release of Ca2+ by noradrenaline and ATP from the same Ca2+ store sensitive to
      both InsP3 and Ca2+ in rat portal vein myocytes.
AB  - 1. Changes in cytosolic free Ca2+ concentration ([Ca2+]i) induced by
      noradrenaline (NA) and ATP were investigated using indo-1 microspectrofluorimetry
      in single smooth muscle cells of rat portal vein. 2. Activation of P2x
      purinoceptors by ATP (10 microM) increased [Ca2+]i from 92 +/- 7 nM (n = 18) to
      557 +/- 30 nM (n = 11). In the presence of NA (10 microM), the ATP-induced rise
      in [Ca2+]i was reduced to 23.6 +/- 1.5% (n = 7) of the control response (in the
      absence of NA). 3. Tetracaine (10 microM to 2 mM) inhibited in a concentration
      dependent manner the Ca(2+)-induced Ca2+ release (CICR) evoked by 5 mM caffeine.
      In the presence of 1 mM tetracaine, the rise in [Ca2+]i induced by ATP (10(-8)
      10(-4) M) was strongly inhibited. A tetracaine-resistant rise in [Ca2+]i,
      corresponding to 26.4 +/- 2.3% (n = 14) of control values, was recorded in
      response to 10 microM ATP. 4. The amplitude of the NA-induced [Ca2+]i rise
      depended on NA concentrations (10(-8)-10(-5) M) and was not modified by
      tetracaine (1 mM). 5. This study suggests that Ca2+ ions released through the
      InsP3 receptor-channel upon NA application do not activate CICR and the InsP3-
      and Ca(2+)-sensitive Ca2+ store appears to represent, at least functionally, a
      single releasable Ca2+ pool.

PMID- 7623276
TI  - Sustained calcium influx activated by basic fibroblast growth factor in Balb-c
      3T3 fibroblasts.
AB  - 1. We have investigated the ionic events elicited in Balb-c 3T3 fibroblasts by
      basic fibroblast growth factor (bFGF), a peptide that binds to membrane receptors
      with tyrosine kinase activity and has a mitogenic action on many cell types. The
      peptide (0.2-100 ng ml-1) caused the appearance of an inward current, as observed
      in whole-cell patch-clamp experiments at a holding potential of -50 mV, that
      could last for tens of minutes and had a peak density of 4.6 +/- 2.6 pA pF-1. The
      reversal potential was 18.8 +/- 16.7 mV. 2. The current was reversibly abolished
      by removal of bFGF from the external bath. Inhibition of low-affinity FGF
      receptors had no effect on the activation of the inward current; it was
      completely abolished when cells were pre-incubated with tyrphostin or 5'
      methylthioadenosine (MTA), two inhibitors of the tyrosine kinase activity of the
      high-affinity FGF receptors. The inward current was not activated by the emptying
      of internal calcium stores, as tested with 200 nM thapsigargin. 3. Values of peak
      current density comparable to control ones were obtained when either all Na+ ions
      or all Ca2+ ions were removed from the external solution; when both ions were
      completely removed, no inward current could be observed. The inward current was
      not affected by 2 microM nifedipine, and was reversibly blocked by the imidazole
      derivative SK&F 96365-A. 4. Measurements of free intracellular calcium
      concentration ([Ca2+]i) with the dye fura-2 showed that bFGF elicited sustained
      increases in [Ca2+]i that were completely dependent on external calcium and on
      the presence of the agonist and could last more than 1 h. 5. Single channel
      currents (conductance 7.9 pS) in response to bFGF stimulation could be recorded
      in the cell-attached configuration with 100 mM CaCl2 in the pipette. When the
      resting potential was brought near to 0 mV by external perfusion in a high-K+
      solution, Vrev was about 0 mV. 6. We conclude that in Balb-c 3T3 cells bFGF
      induces an inward current that is carried at least partially by Ca2+ ions; this
      current in turn causes a long-lasting increase in intracellular Ca2+
      concentration. The amplitude and time course of these bFGF-activated ionic events
      are compatible with their involvement in the control of cell proliferation.

PMID- 7623277
TI  - Inhibitory effect of muscarinic receptor activation on Ca2+ channel current in
      smooth muscle cells of guinea-pig ileum.
AB  - 1. The effect of muscarinic receptor stimulation on voltage-gated calcium channel
      currents was examined in whole-cell voltage-clamped smooth muscle cells of the
      guinea-pig ileum. 2. In cells voltage clamped at -60 mV and in which calcium
      channel currents (ICa) were elicited repeatedly by depolarizing pulses (25 ms
      duration, 0.25 Hz frequency) to 0 mV, carbachol (CCh, 10 microM) induced an
      inward current (ICCh) and were suppressed ICa, in a biphasic manner; an initial
      transient component was followed by a more sustained one. 3. A calcium channel
      current (IBa), when Ba2+ was used as a charge carrier, was also suppressed by CCh
      in a biphasic manner, as with ICa. The sustained phase of the IBa suppression was
      significantly smaller than that of the ICa suppression, suggesting that Ca2+
      entry exerts a potentiating effect on the current suppression. 4. CCh had little
      or no effect on calcium channel currents (ICa and IBa) in cells dialysed with a
      pipette solution containing EGTA (20 mM). 5. Inclusion of GDP-beta-S (1 mM) in
      the pipette solution abolished ICCh and the suppression of IBa. With GTP-gamma-S
      (10 microM) in the pipette, the sustained phase of the IBa suppression remained
      almost unchanged even after removal of CCh. 6. Pretreatment with 2 micrograms ml
      1 pertussis toxin (PTX), which abolished ICCh, did not change noticeably the
      initial transient and sustained phases of IBa suppression. 7. Neomycin (100
      microM) or heparin (5 mg ml-1) in the pipette each abolished the initial
      transient component of ICCh as well as the initial transient phase of IBa
      suppression. 8. The biphasic effect of CCh on IBa was observed in the presence of
      either staurosporine (1 microM) or 1-(5-isoquinolinesulphonyl)-2-methylpiperazine
      (100 microM). Phorbol 12-myristate 13-acetate and phorbol 12,13-dibutyrate (up to
      10 microM) had no inhibitory effect on ICa and IBa. 9. The results suggest that
      stimulation of the muscarinic receptor causes a biphasic suppression of the
      voltage-gated calcium channel currents through a PTX-insensitive G protein in
      guinea-pig ileal smooth muscle cells. The initial transient phase may be brought
      about by the release of Ca2+ from internal storage sites, and the sustained phase
      by a Ca(2+)-dependent mechanism which is independent of the phosphatidylinositol
      pathway.

PMID- 7623278
TI  - Two distinct functional effects of protein phosphatase inhibitors on guinea-pig
      cardiac L-type Ca2+ channels.
AB  - 1. The effects of the phosphatase inhibitors okadaic acid and calyculin A on
      single guinea-pig ventricular L-type Ca2+ channels were studied. The inactive
      derivative norokadaone was used as a negative control. 2. The two known effects
      of cAMP-dependent stimulation are mimicked by the phosphatase inhibitors to a
      varying extent. Only okadaic acid promotes the high-activity gating mode ('mode
      2'), while calyculin A increases channel availability to a larger extent. As
      revealed by kinetic analysis of slow gating, the two phosphatase inhibitors
      retard a slow rate constant, which is assumed to represent exit from the
      available state by dephosphorylation. Norokadaone was inactive in both regards.
      3. Mode 2 gating elicited by very positive prepulses is augmented by okadaic
      acid, and mode 2 lifetime is prolonged. Calyculin A fails to affect these
      parameters. Thus, voltage-facilitated mode 2 gating reveals the same
      pharmacological properties as the mode 2 sweeps observed using conventional pulse
      protocols. 4. The results are interpreted in terms of the different sensitivity
      of protein phosphatase subtypes towards the inhibitors: channel availability
      appears to be controlled by a phosphorylation site dephosphorylated by a type 1
      like phosphatase, while mode 2 gating is coupled to a distinct site,
      dephosphorylated by a type 2A-like phosphatase.

PMID- 7623279
TI  - Change of Na+ pump current reversal potential in sheep cardiac Purkinje cells
      with varying free energy of ATP hydrolysis.
AB  - 1. The Na(+)-K+ pump current, Ip, of cardioballs from isolated sheep cardiac
      Purkinje cells was measured at 30-34 degrees C by means of whole-cell recording.
      2. Under physiological conditions Ip is an outward current. Experimental
      conditions which cause a less negative free energy of intracellular ATP
      hydrolysis (delta GATP) and steeper sarcolemmal gradients for the pumped Na+ and
      Cs+ ions evoked an Ip in the inward direction over a wide range of membrane
      potentials. The reversal of the Ip direction was reversible. 3. The inwardly
      directed Ip increased with increasingly negative membrane potentials and amounted
      to -0.13 +/- 0.03 microA cm-2 (mean +/- S.E.M.; n = 6) at -95 mV. 4. The reversal
      potential (Erev) of Ip was studied as a function of delta GATP at constant
      sarcolemmal gradients of the pumped cations. 5. In order to vary delta GATP the
      cell interior was dialysed with patch pipette solutions containing 10 mM ATP and
      different concentrations of ADP and inorganic phosphate. The media were composed
      to produce delta GATP levels of about -58, -49 and -39 kJ mol-1. 6. A less
      negative delta GATP shifted Erev to more positive membrane potentials. From
      measurements of Ip as a function of membrane potential Erev was estimated to be 
      195, -115 and -60 mV at delta GATP levels of approximately -58, -49 and -39 kJ
      mol-1, respectively. The calculated Erev amounted to -224 mV at delta GATP
      approximately -58 kJ mol-1, -126 mV at delta GATP approximately 49 kJ mol-1 and 
      24 mV at delta GATP approximately -39 kJ mol-1. 7. Possible reasons for the
      discrepancy between estimated and calculated Erev values are discussed. 8.
      Shifting delta GATP to less negative values not only altered Erev but also
      diminished Ip at each membrane potential tested. The maximal Ip (Ip,max), which
      can be activated by external Cs+ (Cs+o), decreased under these conditions,
      whereas [Cs+]o causing half-maximal Ip activation remained unchanged. Similarly,
      the voltage dependence of Ip activation by Cs+o was unaffected. 9. It is
      concluded that Erev of Ip varies with delta GATP at constant sarcolemmal
      gradients of the pumped cations. This agrees with thermodynamic considerations.

PMID- 7623280
TI  - The antagonistic effect of K+o and dihydro-ouabain on the Na+ pump current of
      single rat and guinea-pig cardiac cells.
AB  - 1. The antagonistic effect of extracellular potassium ions (K+o) and dihydro
      ouabain (DHO) on the Na(+)-K+ pump current (Ip) was studied in isolated
      ventricular cells. 2. The myocytes were isolated from rats and guinea-pigs, two
      species with different sensitivity towards cardiac glycosides. Ip measurements
      were performed at 32-34 degrees C by means of whole-cell recording. The membrane
      potential was held at -20 mV throughout. 3. The DHO concentration ([DHO])
      required for half-maximal Ip inhibition (apparent KD value, KD') amounted to 2.4
      x 10(-3) and 1.4 x 10(-5) M for rat and guinea-pig myocytes, respectively, at 5.4
      mM K+o. 4. The data suggest one-to-one binding of DHO to the Na(+)-K+ pump and a
      smaller association rate constant, as well as a larger dissociation rate
      constant, for binding of DHO in the rat cells. 5. Ip activation by K+o was nearly
      identical in myocytes of both species and was measured to be half-maximal at
      approximately 1 mM K+o. Half-maximal Ip activation by K+o remained essentially
      unchanged, but Ip decreased in media containing [DHO] near the respective KD' at
      5.4 mM K+o. 6. The concentration-response curve of Ip inhibition by DHO was
      shifted to higher [DHO] at higher [K+]o. KD' increased correspondingly. The slope
      of the curve was unaffected. 7. Ip and KD' displayed a similar dependence on
      [K+]o. 8. KD' was larger in Na(+)-free than in Na(+)-containing media under
      conditions in which the activation of Ip by K+o was nearly the same. 9. It is
      concluded that the antagonism between K+o and DHO, with regard to the activation
      of Ip, is non-competitive. A possible mechanism of the antagonism is discussed.
      The mechanism implies binding of K+o and DHO to different conformational states
      of the Na(+)-K+ pump which are temporarily exposed to the external face of the
      sarcolemma in the pump cycle. The DHO-bound states do not participate in the
      generation of Ip.

PMID- 7623281
TI  - Contribution of ATP-sensitive potassium channels to the electrophysiological
      effects of adenosine in guinea-pig atrial cells.
AB  - 1. Adenosine caused dose-dependent action potential abbreviation in multicellular
      guinea-pig atrial preparations, an action antagonized by glyburide (IC50, 31
      microM) in both physiological and low-chloride superfusate. 2. When 5 mM ATP was
      included in pipettes for whole-cell voltage clamp of isolated guinea-pig atrial
      myocytes, adenosine (10 microM) increased the holding current at -40 mV from 41
      +/- 8 to 246 +/- 31 pA (mean +/- S.E.M., P < 0.01), and glyburide (20 microM)
      returned the holding current to 69 +/- 11 pA (P < 0.01 vs. adenosine alone).
      Acetylcholine (10 microM) also increased the holding current, but its effects
      were not altered by glyburide. 3. Both adenosine and acetylcholine induced an
      additional current component in response to 500 ms voltage steps. Glyburide
      partially inhibited the adenosine-induced current, but did not alter the effect
      of acetylcholine. In the presence of maximally effective acetylcholine
      concentrations, adenosine increased membrane conductance (P < 0.01), although to
      a lesser extent than in the absence of acetylcholine. 4. Single K+ channel
      activity was seen in only one of eight cell-attached patches in the absence of
      adenosine or acetylcholine (0.5 mM Ba2+ in bath and pipette solutions). With
      acetylcholine (10 microM) in the pipette, inwardly rectifying channels
      (conductance, 41 +/- 5 pS) were seen in five of six patches. With adenosine (10
      microM) in the pipette, single-channel activity was seen in twelve of fourteen
      patches with two populations of channels, one similar to that induced by
      acetylcholine and another higher-conductance channel (72 +/- 5 pS) that showed
      less inward rectification. Glyburide (20 microM) suppressed the high-conductance
      channel (68 +/- 2 pS) leaving a single channel type with a conductance of 36 +/-
      5 pS and strong inward rectification. 5. We conclude that K+ATP channels
      contribute to the electrophysiological actions of adenosine on guinea-pig atrium
      in the presence of physiological intracellular ATP levels, and may therefore play
      a role in the cardiac electrophysiological effects of adenosine in the absence of
      myocardial ischaemia.

PMID- 7623282
TI  - Arachidonic acid activation of a new family of K+ channels in cultured rat
      neuronal cells.
AB  - 1. The presence and properties of K+ channels activated by arachidonic acid were
      studied in neuronal cells cultured from the mesencephalic and hypothalamic areas
      of rat brain. 2. Arachidonic acid produced a concentration-dependent (5-50
      microM) and reversible activation of whole-cell currents. 3. In excised membrane
      patches, arachidonic acid applied to the cytoplasmic or extracellular side of the
      membrane caused opening of three types of channels whose current-voltage
      relationships were slightly outwardly rectifying, inwardly rectifying and linear,
      and whose single channel slope conductances at +60 mV were 143, 45 and 52 pS,
      respectively. 4. All three currents were K+ selective and blocked by 2 mM Ba2+
      but not by other K+ channel blockers such as tetraethylammonium chloride, 4
      aminopyridine and quinidine. The outwardly and inwardly rectifying currents were
      slightly voltage dependent with higher channel activity at more depolarized
      potentials. 5. Arachidonic acid activated the K+ channels in cells treated with
      cyclo-oxygenase and lipoxygenase inhibitors (indomethacin and
      nordihydroguaiaretic acid), indicating that arachidonic acid itself can directly
      activate the channels. Alcohol and methyl ester derivatives of arachidonic acid
      failed to activate the K+ channels, indicating that the charged carboxyl group is
      important for activation. 6. Certain unsaturated fatty acids (linoleic, linolenic
      and docosahexaenoic acids), but not saturated fatty acids (myristic, palmitic,
      stearic acids), also reversibly activated all three types of K+ channel. 7. All
      three K+ channels were activated by pressure applied to the membrane (i.e.
      channels were stretch sensitive) with a half-maximal pressure of approximately 18
      mmHg. The K+ channels were not blocked by 100 microM GdCl3. 8. A decrease in
      intracellular pH (over the range 5.6-7.2) caused a reversible, pH-dependent
      increase in channel activity whether the channel was initially activated by
      arachidonic acid or stretch. 9. Glutamate, a neurotransmitter reported to
      generate arachidonic acid in striatal neurons, did not cause activation of the K+
      channels when applied extracellularly in cell-attached patches. 10. It is
      suggested that the K+ channels described here belong to a distinct family of ion
      channels that are activated by either fatty acids or membrane stretch. Although
      the physiological roles of these K+ channels are not yet known, they may be
      involved in cellular processes such as cell volume regulation and ischaemia
      induced elevation of K+ loss.

PMID- 7623284
TI  - Volume-activated chloride channels in rat parotid acinar cells.
AB  - 1. Rat parotid acinar cells undergo a regulatory volume decrease in response to
      hypotonically induced cell swelling that is sensitive to K+ and Cl- gradients. To
      investigate the potential mechanisms involved, the whole-cell patch-clamp
      technique was used to characterize a volume-sensitive Cl- channel in rat parotid
      acinar cells. 2. Exposure of cells to a hyposmotic gradient induced large Cl-
      currents that exhibited outward rectification and were not affected by membrane
      potential or the absence of intracellular Ca2+. Low external pH increased the
      currents at all potentials without affecting current kinetics. These currents
      were nearly abolished when the cells were in hypertonic conditions. This decrease
      in the current amplitude was correlated with a decrease in the cell size. 3. The
      volume-sensitive currents displayed little or no time dependence, whereas Ca(2+)
      activated Cl- channels, present in the same cells, displayed slow activation
      kinetics and large, time-dependent tail currents upon repolarization to the
      holding potential. 4. The reversal potential of the osmotically activated
      channels was close to the predicted chloride equilibrium potential and was
      sensitive to the physiological extracellular Cl- concentration ([Cl-]o). The
      relationship between reversal potential and [Cl-]o was fitted to a modified
      Nernst equation with a slope of 51 mV per decade, consistent with a Cl- selective
      conductance. 5. The anion permeability sequence of the channel, obtained from the
      shifts of the reversal potentials of the volume-sensitive Cl- current, was: SCN-
      > I- > NO-3 > Br- > Cl- > formate > propionate = methanesulphonate = acetate > or
      = F- > or = butyrate > valerate > gluconate = glucuronate = glutamate. 6. The
      current through the volume-sensitive channels was inhibited by the Cl- channel
      blocker SITS (4-acetamido-4'-isothiocyanatostilbene-2,2'-disulphonic acid) in a
      voltage-dependent manner. 7. We conclude that rat parotid acinar cells express an
      outwardly rectifying Cl- current that can be activated by swelling under
      hypotonic conditions. This Cl- conductance may be an element of the cellular
      mechanisms of volume regulation in exocrine glands.

PMID- 7623283
TI  - Characterization of single potassium channels in mouse pancreatic acinar cells.
AB  - 1. Single K(+)-selective channels with a conductance of about 48 pS (pipette, 145
      mM KCl; bath, 140 mM NaCl + 4.7 mM KCl) were recorded in the patch-clamp whole
      cell configuration in isolated mouse pancreatic acinar cells. 2. Neither
      application of the secretagogues acetylcholine (second messenger, inositol 1,4,5
      trisphosphate) or secretin (second messenger, cAMP), nor addition of the
      catalytic subunit of protein kinase A to the pipette solution changed the
      activity of the 48 pS K+ channel. 3. Intracellular acidification with sodium
      propionate (20 mM) diminished activity of the 48 pS channel, whereas channel open
      probability was increased by cytosolic alkalization with 20 mM NH4Cl. 4. BaCl2 (5
      mM), TEA (10 mM) or apamin (1 microM) added to the bath solution had no obvious
      effect on the kinetics of the 48 pS channel. Similarly, glibenclamide and
      diazoxide failed to influence the channel activity. 5. When extracellular NaCl
      was replaced by KCl, whole-cell recordings revealed an inwardly rectifying K+
      current carried by a 17 pS K+ channel. 6. The inwardly rectifying K+ current was
      not pH dependent and could largely be blocked by Ba2+ but not by TEA. 7. Since
      the 48 pS K+ channel is neither Ca2+ nor cAMP regulated, we suggest that this
      channel could play a role in the maintenance of the negative cell resting
      potential.

PMID- 7623285
TI  - Associative EPSP--spike potentiation induced by pairing orthodromic and
      antidromic stimulation in rat hippocampal slices.
AB  - 1. Pairing low-frequency orthodromic stimulation with high-frequency antidromic
      conditioning of pyramidal cells in area CA1 of the rat hippocampus resulted in
      long-lasting potentiation of the extracellular population spike of the cells,
      without an accompanying increase in the extracellular excitatory postsynaptic
      potential (EPSP), indicating an increase in EPSP-spike (E-S) coupling, also
      called E-S potentiation. 2. The amplitude of the antidromically conditioned E-S
      potentiation took up to 60 min to reach its peak, much longer than synaptic long
      term potentiation (LTP) induced by orthodromic tetanic stimulation. 3. The
      population spike amplitude of a control orthodromic input, which stimulated a
      separate set of fibres and which was inactive during the pairing, was also
      increased in over half the slices tested. That it can affect a silent pathway
      suggests that antidromically conditioned E-S potentiation is not generated
      locally at tetanized synapses. 4. Bath application of 50 microM D,L-2-amino-5
      phosphonovaleric acid (AP5) blocked induction of antidromically conditioned E-S
      potentiation. After washing out the AP5, the same stimulation resulted in
      population spike increases. This suggests that activation of the NMDA subtype of
      glutamate receptor is necessary for the induction of this form of E-S
      potentiation. 5. Application of 10 microM picrotoxin and/or 10 microM
      bicuculline, which block inhibition mediated by gamma-aminobutyric acid A (GABAA)
      receptors, did not reduce antidromically conditioned E-S potentiation. Thus,
      plasticity in GABAA-mediated inhibition cannot account for the increased
      population spike amplitude. 6. E-S potentiation did not increase the amplitude of
      either extracellular or intracellular EPSPs recorded at the cell body.

PMID- 7623286
TI  - The perforant path projection to hippocampal area CA1 in the rat hippocampal
      entorhinal cortex combined slice.
AB  - 1. The perforant path projection from layer III of the entorhinal cortex to CA1
      of the hippocampus was studied within a hippocampal-entorhinal combined slice
      preparation. We prevented contamination from the other main hippocampal pathways
      by removal of CA3 and the dentate gyrus. 2. Initially the projection was mapped
      using field potential recordings that suggested an excitatory sink in stratum
      lacunosum moleculare with an associated source in stratum pyramidale. 3. However,
      recording intracellularly from CA1 cells, stimulation of the perforant path
      produced prominent fast GABAA and slow GABAB IPSPs often preceded by small EPSPs.
      In a small number of cells we observed EPSPs only. 4. CNQX blocked excitatory and
      inhibitory responses. This indicated the presence of an intervening excitatory
      synapse between the inhibitory interneurone and the pyramidal cell. 5. Focal
      bicuculline applications revealed that the major site of GABAA inhibitory input
      was to stratum radiatum of CA1. 6. The inhibition activated by the perforant path
      was very effective at reducing simultaneously activated Schaffer collateral
      mediated EPSPs and suprathreshold-stimulated action potentials. 7. Blockade of
      fast inhibition increased excitability and enhanced slow inhibition. Both
      increases relied upon the activation of NMDA receptors. 8. Perforant path inputs
      activated prominent and effective disynaptic inhibition of CA1 cells. This has
      significance for the output of hippocampal processing during normal behaviour and
      also under pathological conditions.

PMID- 7623287
TI  - Region-specific regulation of neuropeptide mRNAs in rat limbic forebrain neurones
      by aldosterone and corticosterone.
AB  - 1. We have determined in adrenalectomized male rats the effects of clamping
      plasma corticosterone and aldosterone at various concentrations on corticotropin
      releasing hormone (CRH), neurotensin/neuromedin N (NT/N) and proenkephalin (pENK)
      mRNAs in the hypothalamus and amygdala using semi-quantitative in situ
      hybridization. 2. Corticosterone differentially regulated the levels of CRH and
      NT/N but not pENK mRNA. These effects were cell specific. CRH mRNA was reduced in
      the hypothalamic paraventricular nucleus (PVH), but increased in the central
      nucleus of the amygdala and bed nuclei of the stria terminalis. NT/N mRNA was
      never seen in the PVH, whereas levels increased in the central nucleus of the
      amygdala, but were unaffected in the lateral hypothalamic area. In those regions
      expressing pENK mRNA, levels were unaffected in all treatment groups. 3. CRH mRNA
      in both the central nucleus of the amygdala and PVH, and NT/N mRNA in the central
      nucleus of the amygdala were most sensitive to plasma corticosterone
      concentrations of less than 120 ng ml-1, i.e. those seen away from the peak of
      the diurnal rhythm. In adrenalectomized animals CRH mRNA in both the central
      nucleus of the amygdala and PVH could be set at levels usually seen in intact
      animals by the same plasma concentration of corticosterone. 4. The levels of CRH
      mRNA in the PVH and the central nucleus of the amygdala were closely correlated,
      while CRH and NT/N mRNA levels were similarly correlated in the central nucleus
      of the amygdala suggesting the existence of a common regulatory mechanism. The
      ED50 of their responses to corticosterone and correlations with thymus weight
      suggested the operation of glucocorticoid (type II) receptor mechanisms. 5. In
      the absence of corticosterone, aldosterone increased CRH and NT/N mRNA
      accumulation in the central nucleus of the amygdala, and increased CRH but not
      NT/N mRNA accumulation in the PVH. Aldosterone also blunted the dose-response
      effects of corticosterone on CRH and NT/N mRNA levels in the central nucleus of
      the amygdala, but not in the PVH. 6. These results suggest that, in intact
      animals, adrenal steroids play a major role in maintaining the levels of
      neuropeptide mRNAs in the PVH, bed nuclei of the stria terminalis and central
      nucleus of the amygdala. The results underscore the importance of cell-specific
      mechanisms operating to regulate the expression of neuropeptide genes in
      different cell types in response to diverse physiological conditions.

PMID- 7623288
TI  - Mechano-sensitive linkage in excitation-contraction coupling in frog skeletal
      muscle.
AB  - 1. Single skeletal muscle fibres of Xenopus laevis were used to investigate the
      involvement of a mechano-sensitive link in excitation-contraction coupling (EC
      coupling). 2. Fibres were stimulated by intermittent tetani until tension fell to
      about 40% of its initial level. Fibres were then stressed either by briefly
      stretching the fibres to 120% of their resting length or by exposing them to
      hypotonic Ringer solution ([NaCl] reduced to 80%) for 5 min. 3. In six of thirty
      five stretched fibres and in all fourteen fibres exposed to hypotonic solution, a
      long-lasting depression of tension ensued. Tetanic tension then recovered slowly,
      often taking more than 10 h to return to its initial level. 4. During the period
      of minimal tension production, 12 mM caffeine induced a maximum contracture; 190
      mM K+ induced a contracture larger than previous or subsequent tetani, and
      perchlorate (1 mM) slightly augmented tetanic tension. 5. Neither protease
      inhibitors nor a protein synthesis inhibitor altered the long-lasting period of
      tension depression and slow recovery. A free-radical scavenger was also without
      effect. 6. It is concluded that there is a mechano-sensitive link involved in EC
      coupling which can be damaged easily in fatigued muscle fibres.

PMID- 7623289
TI  - Extracellular and intracellular alkalinization and the constriction of rat
      cerebral arterioles.
AB  - 1. Direct observations of perfused cerebral arterioles in vivo and in vitro have
      demonstrated that alkalinization of blood or cerebrospinal fluid (CSF) causes
      arteriolar constriction. Inasmuch as such alkalinizations lead to increases in
      intracellular pH (pHi) as well as interstitial pH (pHo), it is possible that
      increases in either pHi or pHo (or both) underlie alkalinization-induced cerebral
      vasoconstriction. In order to test the hypothesis that changes in pHi alone
      underline alkalinization-induced cerebral vasoconstriction, we simultaneously
      measured vessel diameter and pHi (using the pH-sensitive dye, SNAFL) in isolated
      cerebral arterioles from adult rats during imposed alterations in pHo and pHi. 2.
      Penetrating cerebral arterioles from the distribution of the middle cerebral
      artery were hand dissected, cannulated on one end and occluded distally. Vessels
      were inflated hydrostatically to 60 cmH2O under no-flow conditions. Confocal
      microscopy verified specific pH-sensitivity dye staining of the vascular smooth
      muscle cells within the vessel wall. 3. Extracellular alkalinization from pH 7.3
      to 7.8 caused pHi to increase by 0.06 +/- 0.01 of a pH unit, and vessel diameter
      to decrease by 21.8 +/- 1.8% (mean +/- S.E.M.). 4. Intracellular alkalinization
      at constant pHo was produced by exposure to weak bases, including NH3 and
      trimethylamine, or by exposure to, followed by withdrawal of, weak acids,
      including CO2 and acetic acid. None of these treatments evoked vasoconstriction
      even though each of them caused increases in pHi greater than those observed in
      the same vessels during exposure to the pHo 7.8 solution. 5. We conclude that, at
      least in cerebral arterioles, alkalinization-induced vasoconstriction is mediated
      by an increase in pHo, not pHi [corrected].

PMID- 7623290
TI  - Volume-sensitive taurine transport in bovine articular chondrocytes.
AB  - 1. The swelling of bovine articular chondrocytes isolated from, or in situ
      within, cartilage by hypotonic shock rapidly activated the efflux or influx of
      radiolabelled taurine, an amino acid involved in volume regulation in a range of
      other cell types. 2. When chondrocytes were isolated by the use of collagenase
      into media of 280 or 380 mosmol l-1, the activation of taurine efflux was at
      about the osmolarity of the isolating medium, but it was more marked for a given
      hypotonic shock in the cells isolated at the lower osmolarity. The volume of
      chondrocytes following isolation in these two osmolarities was the same,
      suggesting that the cells possess volume regulatory capacity. 3. In isolated
      chondrocytes, the induced pathway had some of the characteristics of a volume
      activated channel, i.e. no transport saturation with increasing substrate
      concentration, and lack of trans acceleration. The pattern of inhibition of the
      volume-activated pathway by pharmacological blockers (e.g. pimozide, [(dihydro
      indenyl)oxy]alkanoic acid (DIOA) and tamoxifen) differed from that described for
      a similar pathway in other cell types. 4. The transport of other potential
      osmolytes (uridine, sorbitol and inositol) was stimulated by cell swelling,
      independent of sodium and inhibited by pimozide with a selectivity ratio of
      taurine, 1.00; uridine, 0.84; sorbitol, 0.66; and inositol, 0.38. The selectivity
      of taurine: inositol was not altered at different cell volumes. 5. The
      intracellular taurine concentration of chondrocytes within cartilage was low
      (about 2 mmol (l cell water)-1) showing a negligible role for taurine as an
      osmolyte during recovery from cell swelling. The swelling-induced loss of taurine
      from chondrocytes in situ was largely inhibited by pimozide and other drugs,
      showing that despite the rigid nature of cartilage, the chondrocytes were
      osmotically sensitive within the extracellular matrix.

PMID- 7623291
TI  - Febrile responses induced in adrenalectomized rats by administration of
      interleukin-1 beta or prostaglandin E2.
AB  - 1. The present study was carried out to investigate the effect of bilateral
      adrenalectomy on fevers induced in rats by systemic injection of interleukin-1
      beta (IL-1 beta) or by central injection of prostaglandin E2 (PGE2). 2.
      Intraperitoneal (I.P.) injections of two doses of IL-1 beta (0.5 and 1.0
      microgram kg-1) induced biphasic fevers in normal control rats in a dose
      dependent manner. Adrenalectomized (ADX) rats showed higher fevers than sham-ADX
      rats after I.P. injection of small doses of IL-1 beta (0.5 micrograms kg-1). This
      fever enhancement was inhibited by acute or chronic glucocorticoid, dexamethasone
      (DEX), treatment. In contrast, there was no significant difference between fevers
      induced in ADX and sham-ADX rats by I.P. injection of large doses of IL-1 beta
      (1.0 g kg-1). 3. Dose-dependent fevers were observed in normal control rats after
      injections of several doses of PGE2 (5, 25 and 100 ng) into the preoptic
      hypothalamic area (POA). The injection of a large dose of PGE2 (100 ng) into the
      POA led to a lower fever in ADX rats, compared with that in sham-ADX rats. This
      fever in ADX rats was increased by acute or chronic treatment with DEX. On the
      other hand, adrenalectomy had no effect on fevers induced by the injections of
      small doses of PGE2 (5 and 25 ng) 4. The injections of PGE2 (100 ng) into the POA
      induced increases in oxygen consumptions in ADX rats that were significantly
      smaller than those in sham-ADX rats, suggesting that the lower PGE2 fever was, at
      least in part, due to attenuated thermogenesis in ADX rats. 5. There was no
      significant difference in plasma osmolality between the ADX and the sham-ADX
      rats. The ADX rats were given 0.9% salt water instead of tap water. 6. These
      results suggest that endogenous glucocorticoid is one of the important modulators
      of the IL-1-induced and the PGE2-induced fevers in rats.

PMID- 7623292
TI  - Changes in the effect of magnetic brain stimulation accompanying voluntary
      dynamic contraction in man.
AB  - 1. The soleus (Sol) H reflex was conditioned by magnetic stimulation of the
      contralateral motor cortex at rest and during voluntary contraction in healthy
      human subjects. The intensity of the magnetic stimulus was adjusted so as to have
      no effect on the H reflex at rest. During tonic voluntary contraction the same
      magnetic stimulus produced a facilitation with a short latency and a long
      duration, thus reflecting an increased excitation of Sol motoneurones by the
      magnetic stimulus during voluntary contraction. 2. The amount of reflex
      facilitation produced by brain stimulation within the initial 0.5-1 ms after its
      onset was investigated at different times during dynamic ramp-and-hold plantar
      flexion. The facilitation was largest at the onset of voluntary activity in the
      Sol muscle. It then decreased abruptly within 100 ms after the onset of the
      voluntary contraction. Neither the voluntary Sol activity nor the control H
      reflex decreased at this time. 3. Electrical stimulation of the brain with the
      anode placed lateral to the vertex produced a facilitation of the H reflex, which
      preceded the facilitation evoked by magnetic stimulation by 1-2 ms. The
      facilitation produced by the magnetic stimulus occurred or increased at the onset
      of contraction in relation to rest in all experiments. However, this was the case
      in only two out of eight experiments, when the brain was stimulated electrically.
      4. The size of the reflex facilitation measured at the onset of contraction was
      larger the faster the contraction. Positive correlations were found between the
      size of the facilitation and the peak of the first and second derivative of the
      torque and the peak Sol EMG activity. 5. It is suggested that the observed
      changes in the size of the short-latency reflex facilitation produced by magnetic
      brain stimulation mainly reflects changes in the excitability of corticospinal
      cells, since similar changes were not observed in the size of the unconditioned
      Sol H reflex or in the short-latency reflex facilitation produced by electrical
      brain stimulation. The data support the hypothesis that fast conducting
      corticospinal fibres with monosynaptic projections to spinal motoneurones are
      involved in the initiation of voluntary movement in man.

PMID- 7623293
TI  - Latency of effects evoked by electrical and magnetic brain stimulation in lower
      limb motoneurones in man.
AB  - 1. The latency of effects in the tibialis anterior (TA) and soleus (Sol) muscles
      evoked by electrical and magnetic stimulation of the motor cortex was evaluated
      in human subjects by H reflex testing. Post-stimulus time histograms (PSTHs) were
      established for the discharge of single voluntarily activated motor units and
      motor-evoked potentials (MEPs) in the surface electromyogram. 2. At rest both
      electrical and magnetic stimulation evoked an inhibition of the Sol H reflex at
      the lowest intensities of stimulation. In some subjects a facilitation with an
      earlier onset was seen when increasing the stimulation strength. When the anode
      for the electrical stimulation was placed at the vertex directly above the leg
      motor area, the inhibition or facilitation often had the same latency as when
      evoked by magnetic stimulation. However, when the anode was placed 2-3 cm lateral
      to the vertex, effects evoked by the electrical stimulus often occurred 1-2 ms
      earlier. 3. Short-latency peaks in the PSTH of the discharges of single TA motor
      units also tended to occur earlier when evoked by electrical stimulation with the
      anode lateral to the vertex than when evoked by magnetic stimulation or
      electrical stimulation with the anode at the vertex. 4. In one subject, near
      maximal electrical stimulation evoked MEPs with a latency corresponding to that
      seen following stimulation of the brainstem by electrodes placed bilaterally over
      the mastoid processes approximately 16 cm more distal. Maximal magnetic
      stimulation, in contrast, never resulted in responses with a latency shorter than
      that seen with the weakest electrical stimuli at the vertex. 5. The initial
      facilitation of the Sol H reflex evoked by magnetic stimulation and by electrical
      anodal stimulation at the vertex increased when the subject performed a voluntary
      plantarflexion. In contrast, the earlier facilitation evoked by electrical anodal
      stimulation 2-3 cm lateral to the vertex had the same size both at rest and
      during contraction. 6. We suggest that magnetic stimulation and electrical anodal
      stimulation at the vertex may preferentially activate descending cortical cells
      at, or close to, the cell soma. The initial responses evoked by these two stimuli
      may therefore be influenced by the excitability of the cortical cells. On the
      other hand, electrical stimulation with the anode 2-3 cm lateral to the vertex
      seems to often activate the axons at a deeper level. The initial responses evoked
      by this type of stimulation may therefore not be influenced by the excitability
      of the cortical cells.

PMID- 7623294
TI  - Selective depression of medium-latency leg and foot muscle responses to stretch
      by an alpha 2-agonist in humans.
AB  - 1. In standing humans, toe-up rotation of a platform induces a short-latency
      (SLR) and a medium-latency response (MLR) in both soleus (Sol) and flexor
      digitorum brevis (FDB) muscles. Toe-down rotation evokes a MLR in the tibialis
      anterior (TA). The SLR is the counterpart of the monosynaptic stretch reflex, but
      the origin of the MLR is still debated. By means of tizanidine (an alpha 2
      adrenergic receptor agonist) we tested the hypothesis that the MLR is relayed by
      group II afferent fibres, since animal data indicate that tizanidine or
      stimulation of monoaminergic brainstem centres decrease the excitability of
      spinal interneurones supplied by those fibres. In addition, we compared the
      effect of the drug on these responses with that induced by stabilization of
      posture. 2. Eight subjects received tizanidine (150 micrograms kg-1 orally) or
      placebo, in a single-blind design. Platform rotations were delivered prior to
      administration and for 3 h afterwards. Both TA- and FDB-MLRs decreased in size,
      starting from about 1 h after tizanidine administration. Sol-SLR was unaffected.
      Response latencies were unchanged. Placebo induced no changes in any response. In
      each subject, the extent of TA-MLR depression induced by holding onto a frame and
      by tizanidine was superimposable. 3. The selective effect of tizanidine on MLR
      supports the notion that it is relayed through group II afferent fibres. The
      similar effects of holding and tizanidine on the response suggests that it is
      modulated by monoaminergic centres.

PMID- 7623295
TI  - Prey capture phase of feeding behavior in the pteropod mollusc Clione limacina:
      neuronal mechanisms.
AB  - The prey capture phase of feeding behavior in the pteropod mollusc Clione
      limacina consists of an explosive extrusion of buccal cones, specialized
      structures which are used to catch the prey, and acceleration of swimming with
      frequent turning and looping produced by tail bend. A system of neurons which
      control different components of prey capture behavior in Clione has been
      identified in the cerebral ganglia. Cerebral B and L neurons produce retraction
      of buccal cones and tightening of the lips over them--their spontaneous spike
      activities maintain buccal cones in the withdrawn position. Cerebral A neurons
      inhibit B and L cells and produce opening of the lips and extrusion of buccal
      cones. A pair of cerebral interneurons C-BM activates cerebral A neurons and
      synchronously initiates the feeding motor program in the buccal ganglia. Cerebral
      T neurons initiate acceleration of swimming and produce tail bending which
      underlies turning and looping during the prey capture. Both tactile and chemical
      inputs from the prey produce activation of cerebral A and T neurons. This
      reaction appears to be specific, since objects other than alive Limacina or
      Limacina juice do not initiate activities of A and T neurons.

PMID- 7623296
TI  - Endogenous gonadal, LH and molt rhythms in tropical stonechats: effect of pair
      bond on period, amplitude, and pattern of circannual cycles.
AB  - To investigate the effects of reproduction and associated stimuli on the
      circannual cycles of African stonechats Saxicola torquata axillaris birds were
      held for 29 months in aviaries under a constant equatorial (12.25 h) photoperiod,
      either singly (10 females and 10 males) or in 10 male/female pairs. The birds of
      all 3 groups went through circannual cycles in gonadal size, plasma LH and molt,
      but groups differed with regard to actual reproductive performance. During the
      second cycle, only one of the singly-held females laid eggs and incubated. In
      contrast, in the paired females egg-laying and incubation occurred in all but one
      bird. About 50% of the clutches from paired females contained fertilized eggs
      confirming the expectation of behavioral differences between the paired and
      unpaired birds. However, despite differences in reproductive performance there
      were no differences in either circannual period or duration of reproductive
      phases. Moreover, there was no correlation between number of broods produced per
      season and circannual parameters of the paired females. Therefore, the temporal
      course and, particularly, the period during which reproduction is possible is
      rigidly determined by an endogenous program that is not influenced by
      reproductive performance. A rigid program of this kind may be advantageous in the
      tropics because it prevents prolongation of the breeding season in years with
      favourable conditions which in turn could jeopardize optimal timing of breeding
      in the following year and thus reduce lifetime reproductive success.

PMID- 7623297
TI  - The winner's group: a self-help group for homeless chemically dependent persons.
AB  - The homeless chemically addicted person presents many unique problems that cannot
      be addressed in standard treatment programs. Homeless clients are difficult to
      track and are not consistent in follow-up care. The health and mental health
      conditions found in this population are straining the resources of drug treatment
      programs, hospitals, the criminal justice system, and social agencies that serve
      the homeless (Bassuck, 1991). The Winner's Group located in an inner city soup
      kitchen demonstrates the adaptability and flexibility of nursing practice. The
      nurses exhibited creativity in developing methods to meet the diverse needs of
      homeless chemically addicted persons. The goals and objective that were achieved
      were neither successes nor failures, they were reflections of efforts to make
      lifestyle changes. Some of those persons responded in a very positive manner,
      while others continued to deteriorate. An overall desire was to instill a seed of
      hope and knowledge that there is always a potential for change and that recovery
      from chemical dependency is possible. Nurses who work with the homeless must be
      knowledgeable and realistic about the impact and importance of substance abuse.
      Nontraditional programs that meet the unique needs of a particular setting and a
      particular population can provide an opportunity to gain access to health care
      providers.

PMID- 7623298
TI  - The construction of disorders. Exploring the growth of PTSD and SAD.
AB  - 1. Post-traumatic stress disorder and seasonal affective disorder represent two
      diagnostic entities that have gained tremendous popularity and have, at the same
      time, obscured the fact that humans have somehow managed to endure hardship for
      millennia without "treatment." 2. Nurses stand in the midst of two traditions,
      one of supporting reliance on medical experience and the other, of attending to
      the natural course of human resilience. 3. Nurses must learn about the personal
      and cultural meanings that enable individuals and societies to deal with life in
      constructive, self-enhancing ways, in addition to assisting patients in the
      context of diagnoses.

PMID- 7623299
TI  - Clozaril. An Australian experience.
AB  - 1. Clozaril, an atypical antipsychotic, did not gain approval for use in
      Australia until 1992. Prior to its general release, a trial was conducted in
      three pilot sites to test the efficacy of a monitoring system. 2. Fear of
      litigation among hospital staff was reduced through educational sessions that
      reported on the low incidence of serious side effects and the efficacy of the
      monitoring system. 3. The most common side effect noted with initiation of
      Clozaril was sedation, which persisted for 4 to 6 weeks. Subsequent side effects
      included drowsiness, increased salivation, and tachycardia.

PMID- 7623300
TI  - From a survivor. The emotional experience of genetic testing.
AB  - 1. HD is a family disease, transmitted by an autosomal dominant gene: any child
      of an affected person has a 50:50 chance of developing the disease. 2. The
      average age of onset of symptoms is between 30 and 45. 3. The guidelines for
      genetic testing for HD contain strong recommendations for pre- and posttest
      counseling.

PMID- 7623301
TI  - Nurses helping nurses. Development of internal specialists in long-term care.
AB  - The prevalence of psychiatric disorders and behavioral disturbances among nursing
      home residents, combined with observed deficits in geriatric mental
      health/illness expertise among LTC staff, supports the need for creative
      approaches to improve the knowledge, understanding, and management of such
      problems among LTC providers. The train-the-trainer model described in this
      article proved to be a viable method to providing geriatric mental health
      consultation and training that targets both improved quality of life for
      residents and quality of work life for the staff in charge of residents' care.
      More collaborative efforts among nursing specialists, subspecialists, and
      generalists are needed to empower those who work in LTC to utilize strengths and
      abilities inherent to their positions. Nursing homes nurses, who are all too
      familiar with the problems and challenges of their patient population, may act
      not only as mental health trainers but also as resource persons, role models,
      liaisons with geropsychiatric specialists, and leaders in the application of
      geropsychiatric care principles to residents within their facility, thus
      promoting improved resident and staff care alike.

PMID- 7623302
TI  - NMHA responds negatively to Clinton mental health budget.

PMID- 7623303
TI  - Panic disorder: a personal and nursing perspective.
AB  - Fortunately, the symptoms of PD and agoraphobia now can be managed effectively
      with medication or with a combination of medication and behavioral treatments. It
      is certain that these new treatments will give many patients who were once
      disabled by this disorder the chance to lead normal lives.

PMID- 7623305
TI  - Society for the Study of Fertility annual conference. Dublin, July 1995.
      Abstracts.

PMID- 7623304
TI  - Vicarious traumatization in the work with survivors of childhood trauma.
AB  - 1. Persons working with victims of childhood trauma may experience traumatic
      countertransference and vicarious traumatization. After hearing a patient's
      trauma story, which is a necessary part of childhood trauma therapy, staff may
      experience post-traumatic stress disorder, imagery associated with the patient's
      story and the same disruptions in relationships as the patient. 2. During the
      first 6 months of working with survivors of childhood trauma, common behaviors of
      staff members were identified, including a lack of attention, poor work
      performance, medication errors, sick calls, treatment errors, irreverence,
      hypervigilance, and somatic complaints. 3. Staff working with victims of
      childhood trauma can obtain the necessary staff support through team support, in
      traumatic events, and in a leadership role.

PMID- 7623307
TI  - Development of the sheep ovary during fetal and early neonatal life and the
      effect of fecundity genes.
AB  - In female sheep fetuses, the mesonephros and genital ridge can be identified at
      days 20 and 23 of gestation (term = 145 days), respectively. Moreover oogonia can
      be observed at the genital ridge from as early as day 23. Around day 55 of
      gestation, some germ cells enter meiosis coincident with the arrival of
      mesonephric-derived somatic cells (i.e. the rete ovarii). From day 75, 100, 120
      and 135 of gestation, primordial (one layer of flattened granulosa cells),
      primary (one complete layer of cuboidal granulosa cells; early preantral),
      secondary (preantral) and tertiary (antral) follicles, respectively, develop
      within the innermost regions of the ovarian cortex. During the early neonatal
      period highly variable numbers of antral follicles may be present. After
      examination of Booroola fetuses from day 28 of gestation, it seems that the FecBB
      gene is associated with retarded development of the heart (day 28) mesonephros
      (days 30-40) and from day 30 to early neonatal life, the ovary. With respect to
      the ovary, fewer oogonia (days 30-40), primordial follicles (day 75-90) and
      growing follicles (day 120 to 6 weeks after birth) have been observed in females
      carrying the FecBB gene. By contrast, the FecBB gene is not associated with
      differences in plasma gonadotrophin or immunoreactive inhibin until early
      neonatal life. In Inverdale (I) fetuses heterozygous for the FecXI gene (I+),
      retarded germ cell development was observed at days 40 and 90 of gestation. In
      putative homozygous carriers (II) of the Inverdale gene, germ cell development
      appeared normal until day 100, but thereafter from day 120 normal secondary
      follicles were not observed, although many abnormal follicular-like structures
      were present. In both I+ and II fetuses no obvious differences in gonadotrophin
      concentrations have been noted. Collectively, the evidence suggests that the
      fecundity genes FecBB and FecXI, which affect ovulation rate in sexually mature
      females, are regulating organ differentiation or germ cell maturation or both
      processes during fetal life.

PMID- 7623308
TI  - Melatonin and the development of circadian and seasonal rhythmicity.
AB  - We have investigated whether the maternal melatonin rhythm provides the fetus
      with either a circadian or seasonal 'signal' during development. Our findings
      provide evidence that melatonin can generate and entrain the early evening peak
      in the daily rhythm of fetal breathing movements. In contrast, daily variations
      in maternal and fetal prolactin concentrations are present in pinealectomized
      ewes, are altered by changes in the time of onset of darkness, but are unaltered
      by changes in the phase of the daily melatonin rhythm. The mechanisms that
      generate and control the daily prolactin rhythm before and after birth are
      therefore unknown. It is clear from a number of studies that the duration of the
      nocturnal melatonin signal provides the adult and fetal sheep with photoperiodic
      information. We investigated whether there are differences in the fetal plasma
      concentrations of prolactin in ewes held in long and short photoperiods after
      surgical disconnection of the fetal hypothalamus and pituitary and demonstrated
      that there was a fetal prolactin response to the external photoperiod in sheep
      fetuses in which the hypothalamo-pituitary axis was either intact or surgically
      disconnected. We have suggested that one potential extrahypothalamic site of
      action of maternal melatonin is at the pars tuberalis of the fetal pituitary. It
      appears therefore that there are a number of different mechanisms for the
      neuroendocrine transmission of information about the time of day and duration of
      the external photoperiod to the sheep fetus throughout late gestation.

PMID- 7623306
TI  - The search for the Booroola (FecB) mutation.
AB  - Sheep derived from the Booroola Merino strain carry an autosomal mutation (FecB)
      that increases ovulation rate and litter size. One approach to characterize the
      genetic mutation is to locate the gene using positional cloning. The locus has
      been mapped to a region between genes for secreted phosphoprotein 1 (SPP1) and
      epidermal growth factor (EGF) on sheep chromosome 6. Analysis of possible
      candidate genes have excluded a number of genes associated with control of
      reproduction including genes from chromosome 6. Attempts to define close flanking
      markers and clone the region of DNA containing the mutation are now in progress.
      We have cloned additional markers and developed a linkage map showing that the
      FecB locus maps towards the centromere on chromosome 6. We have developed a yeast
      artificial chromosome (YAC) library for the sheep and begun screening the library
      to identify large DNA clones spanning the FecB region. These will be used to
      locate the mutation and shed light on how the mutation increases ovulation rate
      in Booroola sheep.

PMID- 7623309
TI  - Ontogeny of GnRH systems.
AB  - In all vertebrate species studied, the main central population of GnRH neurones,
      which produces the final messages regulating reproduction, originates outside the
      brain. Early during fetal life, they appear in the olfactory placode epithelium
      and then migrate toward the base of the telencephalon in close association with
      the nervus terminalis, penetrate the brain within the nervus terminalis roots,
      reach their final locations and eventually grow axons toward their targets. Only
      part of this process is documented in ruminants. In the sheep fetus, the
      olfactory placode develops between day 22 and day 26 of gestation, but the first
      GnRH-immunoreactive neurones have been detected only at day 35, associated with
      the extracerebral part of the nervus terminalis. During the next 30-40 days, the
      GnRH neuronal systems progressively invade the brain. In both sexes, most of the
      development, in terms of distribution and morphology of the neurones, appears to
      be completed by the middle of gestation (term being on day 145). On day 85 GnRH
      immunoreactive neuronal systems of male and female fetuses have also been
      reported to be very similar to GnRH neuronal systems of adult females. Attention
      should now be focused on the earliest developmental steps.

PMID- 7623310
TI  - Maternal recognition of pregnancy.
AB  - Enhanced secretion of PGF2 alpha from endometrial explants in vitro in response
      to oxytocin is associated with augmented activities of phospholipase A2,
      phospholipase C and prostaglandin endoperoxide H synthase (PGS). In early
      pregnancy, maintenance of the corpus luteum is associated with an absence of
      pulsatile PGF2 alpha secretion; an increase in endometrial inhibitors of
      phospholipase A2 and PGS contribute to the antiluteolytic alterations of PGF2
      alpha secretion. Linoleic acid is a competitive inhibitor of arachidonic acid
      metabolism by PGS, and microsomal concentrations of free linoleic acid are
      increased in the endometrium of pregnant cattle. The trophoblast produces large
      quantities of interferon tau (IFN-tau). Inhibition of increases in endometrial
      oestradiol receptor mRNA and protein are associated with intrauterine
      administration of recombinant (r) ovine (o) IFN-tau in sheep. Intrauterine
      injections of ovine (b) IFN-tau in cattle (days 14-17) altered endometrial
      function so that secretion of PGF2 alpha from cultured endometrial epithelial
      cells was reduced. Antiluteolytic effects were not expressed in 20% of cows
      receiving IFN-tau or rbIFN-alpha I1 indicating that an inadequate endometrial
      responsiveness may contribute to embryo mortality. IFN-tau may activate a signal
      transduction system similar to that induced by other type I IFNs; activation of
      an intracellular tyrosine kinase ultimately leads to activation of an IFN
      stimulated response element to induce gene transcription. Biological responses
      associated with pregnancy and IFN-tau treatment are integrated into a
      multifactorial antiluteolytic model. Strategies to enhance embryo survival could
      include supplementation with rIFN-tau and alterations in endometrial
      responsiveness to this cytokine through dietary manipulation of lipid metabolism.

PMID- 7623311
TI  - Role of GnRH in the ontogeny and regulation of the fetal hypothalamo-pituitary
      gonadal axis in sheep.
AB  - Adult reproductive ability is to a large extent determined by the appropriate
      development of the reproductive axis during fetal life. Studies have investigated
      the role of the fetal hypothalamus in the ontogeny and regulation of pituitary
      gonadal function during fetal development in sheep. Using immunocytochemistry, we
      examined the ontogeny of gonadotroph development in the pituitary of female sheep
      fetuses. At day 70 of gestation (term = 145 days), only immunopositive LH beta
      cells were present. The number and intensity of staining of these LH beta cells
      had increased by day 100 but had declined again by day 130. Immunopositive alpha
      subunit and FSH beta cells appeared at day 100 of gestation and had further
      increased in number and staining intensity by day 130 of gestation. Treatment of
      fetuses with the GnRH agonist buserelin resulted in desensitization of the fetal
      pituitary gonadotrophs, inhibition of pituitary LH beta and FSH beta mRNA
      expression and a reduction in the number of immunopositive gonadotrophin
      containing cells. Pulsatile GnRH treatment resulted in pituitary-gonadal
      activation and an increase in LH, FSH and testosterone secretion in males. Thus,
      the synthesis and secretion of the gonadotrophins during fetal development is
      critically dependent on the secretion of GnRH from the fetal hypothalamus.
      Inhibition of fetal gonadotrophins by buserelin treatment from day 70 of
      gestation resulted in a 40% reduction in the size of the fetal testis at birth,
      and there were no effects on the fetal ovaries. This reduction in testis size was
      due to a 45% reduction in the number of Sertoli cells. However, when buserelin
      was given between day 70 and day 110 of gestation, there were no effects on
      testis size or morphological development of the testis, suggesting that
      gonadotrophins regulate testicular development during a 'critical window' late in
      gestation. Taken together, these studies provide convincing evidence that GnRH
      plays a central role in the ontogeny and regulation of pituitary-gonadal function
      during fetal life.

PMID- 7623312
TI  - Inhibin and activin in embryonic and fetal development in ruminants.
AB  - Inhibin, activin and follistatin are protein hormones with diverse physiological
      roles. The involvement of inhibin in the regulation of pituitary FSH production
      and secretion in adult males and non-pregnant females is well established.
      However, it is unlikely that inhibin plays a similar role in pregnancy in
      ruminants. Inhibin and activin molecules show a high degree of structural
      similarity to potent growth and differentiation factors of the transforming
      growth factor beta (TGF-beta) superfamily of peptides and their localization in a
      range of embryonic and fetal tissues indicates that they may thus play a role in
      development. Furthermore, the demonstration that follistatin is also present in a
      number of embryonic and fetal tissues and fluids has further implications for the
      actions of activin to which it binds. The role of inhibin, activin and
      follistatin in early development has yet to be established since gene knockout
      experiments have so far proved inconclusive. During mid- and late gestation, high
      concentrations of inhibin are found in the testes and plasma of male fetuses of
      sheep and cattle. Inhibin may play a role in regulating pituitary FSH release in
      late pregnancy, but the very high concentrations of this hormone in ovine fetal
      testes and in male fetal plasma compared with that observed in the fetal ovary
      and female fetal plasma has yet to be explained. The recent observation of high
      concentrations of inhibin, activin and follistatin in amniotic fluid surrounding
      the fetus is intriguing. Excretion via urine or lung liquid is partly responsible
      for the presence of these proteins in amniotic fluid. The fetal membranes and the
      placenta are also possible sources. It remains to be established whether these
      proteins constitute an inactive pool of secreted hormone or whether they have
      other actions in this fetal compartment.

PMID- 7623313
TI  - Development of the gonadotrophic and somatotrophic axes of sheep.
AB  - The hypothalamo-pituitary-gonadotrophic axis develops in the sheep fetus from
      midgestation to late gestation. The GnRH neuronal centres seem to be fully
      developed in the fetus and their localization complies with the adult pattern.
      Pituitary gonadotrophs are responsive to exogenous GnRH and release LH and FSH in
      a pulsatile fashion; the highest concentrations in plasma are found during late
      gestation. In sheep, maturational changes of this axis continue through to the
      prepubertal period. The GnRH neuronal system is established at about 12 weeks of
      age. The pattern of LH and FSH release is characteristic for each gonadotrophin
      depending on age and sex. The responsiveness of the gonadotrophs to GnRH
      increases up to 3 weeks of age. It is concluded that the changes in morphology
      and physiology of the hypothalamo-pituitary-gonadotrophic axis reflect the
      progressive maturation of the central mechanisms involved in the control of
      gonadotrophin secretion throughout fetal and prepubertal growth in sheep.
      Development of the hypothalamo-pituitary-somatotrophic axis begins in the fetus
      around mid-gestation. The central regulation of growth hormone (GH) in the fetus
      probably has a dual character, although the growth hormone releasing hormone
      (GHRH) neuronal system has not yet been observed in sheep. The somatostatin
      neuronal system develops in diverse neuronal centres in the fetus. The
      somatostatin centre involved in hypophysiotrophic functions does not develop
      fully before birth and is established over the first 10 weeks after birth. Plasma
      GH concentrations are very high in the fetus and fall suddenly in the perinatal
      period, and after a temporary increase they decline with age.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7623314
TI  - Distribution of neurotransmitters in the sheep brain.
AB  - Although the general organization of the sheep brain is similar to that of other
      mammals, there are species differences in the fine architecture and
      neurotransmitter distribution. In sheep, perikarya are generally scattered,
      unlike the situation in rodents where they are clustered. The same organization
      is observed in cows and primates. The density of neurones immunoreactive for
      tyrosine hydroxylase in the dorsorostral diencephalon of sheep is lower than in
      rodents; A14 and A15 dopaminergic cell groups do not present a dorsal part. Only
      one adrenergic group, C2, is observed in the dorsomedial medulla oblongata. GnRH
      immunoreactive neurones are mainly found in the anterior hypothalamic-preoptic
      areas, a few being present in the mediobasal hypothalamus. The density of several
      neurones containing neuropeptides (for example vasoactive intestinal polypeptide,
      cholecystokinin and somatostatin) in the caudal brain of sheep is lower than in
      other species and in the forebrain of sheep. These differences contribute to
      different patterns of innervation of brain areas compared with other species. For
      example, the suprachiasmatic nucleus does not present a dense network of fibres
      immunoreactive for 5-hydroxytryptamine and neuropeptide Y as observed in rats.
      These morphological studies constitute information necessary for further
      physiological investigations.

PMID- 7623315
TI  - Gamma amino-butyric acid and the control of GnRH secretion in sheep.
AB  - The release of GnRH from nerve terminals in the median eminence into the portal
      vessels is influenced by factors in the internal and external environment of the
      animal. In the former category are the gonadal steroid hormones oestrogen and
      progesterone which alter the characteristics of GnRH secretion during the
      oestrous and seasonal cycles. These cannot exert their actions directly on the
      GnRH neurones as they do not possess hormone receptors. Therefore, some other
      steroid-sensitive neuronal system must relay this information to the GnRH
      neurones. Gamma amino-butyric acid (GABA) neurones are good candidates for this
      role as they contain steroid hormone receptors and synapse on GnRH neurones.
      Recent studies in ewes have sought to identify a role for GABA in mediating the
      actions of both oestrogen and progesterone on GnRH release. The technique of
      microdialysis was used to monitor GABA concentrations in areas containing GnRH
      cell bodies during the oestrogen-induced surge of GnRH and during progesterone
      negative feedback. Concentrations of this inhibitory neurotransmitter have been
      shown to fall in the former situation where GnRH release is being stimulated, but
      to be increased when progesterone is depressing GnRH release. GABA may also be
      important in mediating the seasonal switch in the negative feedback actions of
      oestradiol. During the anoestrous season, when oestradiol is a potent inhibitor
      of GnRH secretion, specific GABA receptor antagonists can stimulate neurohormone
      release, an action that is not observed in the breeding season when oestrogen is
      much less potent.

PMID- 7623316
TI  - Electrophysiological approach to the hypothalamic GnRH pulse generator.
AB  - The hypothalamic GnRH pulse generator that regulates intermittent GnRH discharge
      into the pituitary portal circulation and thereby modulates pulsatile secretion
      of LH has been recognized as a key determinant of the reproductive function in
      mammals. Thus, various internal, as well as external, factors first modify the
      electrical activity of the GnRH pulse generator, which then alters the pulsatile
      pattern of gonadotrophin secretion and eventually influences reproductive
      function. Here, we describe a procedure that has permitted long-term recording of
      electrophysiological manifestation of the GnRH pulse generator activity and its
      application to our research which uses ovariectomized and cyclic female goats as
      experimental models. We have successfully recorded characteristic increases in
      neuronal activity associated with pulsatile LH secretion from conscious goats by
      means of a multiple unit activity (MUA) recording technique, which is an
      adaptation of that developed originally for use in rhesus monkeys. The unitary
      relationship between periodical increases in MUA (MUA volleys) and LH pulses is
      well maintained under a variety of experimental conditions, providing evidence
      that these MUA volleys are the consequence of GnRH pulse generator activity.

PMID- 7623317
TI  - The preovulatory gonadotrophin-releasing hormone surge: a neuroendocrine signal
      for ovulation.
AB  - Recent studies have demonstrated that an important component of the positive
      feedback response to oestradiol in mammals is an action within the central
      nervous system to induce a large surge in the secretion of gonadotrophin
      releasing hormone (GnRH). This oestradiol-induced neuroendocrine signal for
      ovulation has been best characterized in ewes. The GnRH surge is high in
      amplitude; the amount secreted increases on average more than 40 times above the
      pre-surge baseline value. The initial increment in GnRH secretion precedes or
      coincides with the onset of the LH surge. The GnRH surge is of extended duration,
      lasting far longer than the preovulatory LH surge. A molecular variant of GnRH,
      which is less active biologically than native GnRH, is co-secreted at the time of
      the surge, but termination of the LH surge cannot be accounted for by a change in
      biological activity of the secreted GnRH. Generation of the GnRH surge appears to
      follow a characteristic progressive change in the pattern of GnRH in portal
      blood. High concentrations of oestradiol initially stimulate the secretion of
      GnRH between pulses; this is followed by augmentation of both pulsatile and
      interpulse GnRH release producing the rising limb of the surge. Finally, recent
      experiments have indicated that the local application of oestradiol to the
      ventromedial nucleus of the hypothalamus is sufficient to stimulate the GnRH
      surge, suggesting a key rol for this hypothalamic area in the generation of this
      neuroendocrine signal for ovulation.

PMID- 7623318
TI  - Molecular biology of gonadotrophins.
AB  - Regulation of gonadotrophin synthesis involves a complex interaction between
      hypothalamic and gonadal hormones. Chronic administration of oestrogens and
      androgens to gonadectomized animals blocked the postcastration rise in amounts of
      mRNA encoding gonadotrophin subunits. Removal of endogenous GnRH decreased
      amounts of mRNA encoding gonadotrophin subunits. Pulsatile administration of GnRH
      to GnRH-deficient animals increased amounts of mRNA encoding gonadotrophin
      subunits. Studies using transgenic mice and transient transfection assays
      identified at least eight cis-acting DNA sequences in the proximal 350 bp of 5'
      flanking sequence of the human alpha subunit gene that directed expression to
      gonadotrophs or conferred responsiveness to oestrogens, androgens or GnRH. Unique
      DNA-binding proteins were also identified which directed expression of the human
      alpha subunit gene specifically to the pituitary. Pituitary cell lines that
      express bovine gonadotrophin subunit genes are not currently available; thus,
      relatively little is known about the molecular mechanisms that regulate
      expression of bovine gonadotrophin subunit genes. Recent studies with transgenic
      mice harbouring bovine alpha, LH beta, or FSH beta subunit transgenes revealed
      that DNA sequences important for gonadotroph-specific expression and hormonal
      regulation resided within the proximal 5' flanking sequences.

PMID- 7623320
TI  - Dopaminergic control of LH secretion by the A15 nucleus in anoestrous ewes.
AB  - Annual variations in the secretion of LH are responsible for seasonal changes in
      ovulatory activity in ewes. This hormonal pattern reflects an increase in the
      intensity of the negative feedback exerted by oestradiol under long days.
      Neuropharmacological studies have shown that this inhibition of LH secretion
      involves activation of catecholaminergic systems from preoptic and mediobasal
      hypothalamus (MBH) by oestradiol during anoestrus, and that 5-hydroxytryptamine
      inputs may also play a role. Within the MBH, the most important structures appear
      to be the retrochiasmatic region of the hypothalamus, which contains the A15
      dopaminergic nucleus, and the median eminence, which contains the axon terminals
      of the GnRH cells controlling the pulsatile release of LH. In ovariectomized ewes
      in which oestradiol tonically inhibits LH secretion during the anoestrous season,
      LH pulse frequency is increased when the cells of the A15 nucleus are destroyed.
      The median eminence and other mediobasal structures contain more catecholamines
      and their metabolites under long days than under short days. Microdialysis of the
      A15 nucleus in vivo during long days revealed increased catecholaminergic
      activity under oestradiol treatment due to stimulation of tyrosine hydroxylase,
      the rate-limiting enzyme in the pathway of catecholaminergic synthesis. Tyrosine
      hydroxylase activity within the median eminence is increased under the various
      photoperiodic regimens that inhibit LH secretion. Neurochemical changes in the
      A15 nucleus and median eminence, in response to photoperiodic or oestradiol
      treatments, suggest a functional relationship which acts at the level of the GnRH
      axon terminals.

PMID- 7623319
TI  - Neurochemical identity of neurones expressing oestrogen and androgen receptors in
      sheep hypothalamus.
AB  - Gonadal steroids exert important feedback influences on hypothalamic neurones
      involved in regulating reproductive behaviour and pituitary hormone secretion.
      The recent development of antibodies specific for individual gonadal steroid
      receptors has been of great use in determining precisely which cells in the
      hypothalamus express androgen, oestrogen and progesterone receptors. In the sheep
      brain, both oestrogen and androgen receptor antibodies have been used
      successfully and the distribution of cells expressing both receptors has now been
      determined in ewes and rams, respectively. In addition, the predominantly nuclear
      localization of the steroid receptors has enabled double-labelling
      immunocytochemical procedures to determine the neurochemical phenotype of
      neurones expressing the steroid receptor. Work in the sheep hypothalamus shows
      that gonadotrophin-releasing hormone neurones do not possess oestrogen or
      androgen receptors. However, substantial numbers of cells containing oestrogen
      receptors in the preoptic area of ewes contain the inhibitory neurotransmitter
      gamma aminobutyric acid, while most oestrogen receptor-immunoreactive neurones in
      the ventromedial nucleus synthesize the inhibitory neuropeptide somatostatin.
      Androgen receptors have been detected in many of the ventromedial somatostatin
      neurones in rams. In contrast, the neurochemical phenotype of the great majority
      of oestrogen and androgen receptor-immunoreactive cells in the arcuate nucleus
      remains unknown. The identification of the neurotransmitters and neuropeptides
      synthesized by neurones possessing androgen and oestrogen receptors in different
      regions of the ovine hypothalamus provides a neuroanatomical basis for
      understanding the mechanisms by which gonadal steroids regulate reproductive
      function.

PMID- 7623321
TI  - Matrix metalloproteinases and their tissue inhibitors at the ovine trophoblast
      uterine interface.
AB  - Trophoblast invasiveness in ruminants is limited to fusion of migrating
      binucleate cells with uterine epithelium, but considerable tissue remodelling and
      angiogenesis occurs within the endometrium at implantation. Such processes are
      elsewhere associated with an altered balance of matrix metalloproteinases (MMPs)
      and their tissue inhibitors (TIMPs). ProMMPs-1, -2, -3 are secreted by cultured
      ovine endometrial stromal, but not epithelial, cells and expression of proMMP-1
      and proMMP-3 is inhibited by interferon tau, the dominant preimplantation
      trophoblast product, independently of its effects on prostaglandin production.
      Messenger RNA for TIMP-1 and TIMP-2 is expressed in endometrium throughout the
      oestrous cycle and early pregnancy. Both TIMP-1 mRNA (0.9 kb transcript) and TIMP
      2 mRNA (1.0 kb transcript) expression increase at day 12 through to day 20,
      suggesting a role in preventing trophoblast invasion. Expression of the 3.5 kb
      transcript for TIMP-2 decreases from day 16 and is undetectable on day 20.
      Uterine flushings from both nonpregnant and pregnant ewes on day 16 after oestrus
      contain proMMP-2, possibly transudated from plasma, and proMMP-9, but
      concentrations are higher in pregnancy. These enzymes are also detected in
      conditioned medium following culture of trophoblasts at days 16-20. Whether the
      trophoblast MMPs have a role in implantation in sheep remains to be established.
      The production of MMPs and TIMPs in the endometrium and the changes associated
      with implantation events suggest that they contribute to the marked edometrial
      remodelling associated with early placentation.

PMID- 7623322
TI  - Negative feedback regulation of the secretion and actions of GnRH in male
      ruminants.
AB  - The roles of testicular hormones in the negative feedback regulation of the
      secretion and actions of GnRH in male domestic ruminants are reviewed,
      concentrating mainly on research conducted with rams. Testicular steroids have
      major feedback actions directly at the hypothalamus to inhibit the secretion of
      GnRH, although it is apparent that, under certain circumstances, the steroids
      also have actions directly at the pituitary gland. Further research is necessary
      to delineate these actions and to determine the contribution of testosterone and
      its primary metabolites, dihydrotestosterone and oestradiol, to negative feedback
      on the hypothalamo-pituitary unit. Since GnRH neurones do not possess receptors
      for steroids, testicular steroids must evoke other neuronal pathways to influence
      GnRH producing neurones. While the opioids may be important in this regard, it is
      necessary to determine which other neuronal pathways may also be involved to
      understand fully the mechanism of action of testicular steroids. It appears that
      the feedback regulation of the secretion of LH can be accounted for by testicular
      steroids, whereas the secretion of FSH is influenced by inhibin and steroids, and
      possibly the recently isolated proteins follistatin and activin. The actions of
      inhibin to suppress the secretion of FSH occur at the pituitary gland and not on
      the synthesis or secretion of GnRH. There is a complex interaction between
      testosterone and inhibin in the control of FSH secretion that results in
      synergistic effects during the non-breeding season but not during the breeding
      season. Activin has been shown to have FSH-stimulating properties and follistatin
      has been shown to have FSH-inhibiting properties, but it is unknown if these
      proteins play a physiological role in the feedback regulation of FSH in male
      domestic ruminants.

PMID- 7623323
TI  - Oviduct proteins in fertilization and early embryo development.
AB  - The oviduct controls the environment in which the gametes are transported and
      fuse, and in which embryonic development begins. The ultrastructural topography
      of the ampulla and isthmus is similar, consisting of ciliated and secretory
      cells, but a different array of proteins is secreted by each segment along with
      various serum components. Amino acids are selectively secreted by the oviduct;
      these amino acids probably interact with the gametes or embryo to facilitate the
      processes of fertilization and development. An oviduct-specific glycoprotein is
      synthesized by the ampulla of sheep and cattle in response to oestrogen and
      secreted mainly from day-1 to day 3 of the ovarian cycle. This oestrus-associated
      glycoprotein (EGP) has a variable molecular mass of 80-97 kDa and a pI value
      ranging from 4.7 to 5.5. The bovine (b) and ovine (o) EGP genes are 95.5%
      identical and consist of 1560 base pairs encoding 519 amino acids containing one
      N-linked and several O-linked glycosylation sites. The terminal glycosides are N
      acetylglucosamine and galactose-N-acetylgalactosamine for bEGP, and fucose,
      galactose and sialic acid residues are also identified for oEGP. EGP binds to
      zona pellucida and blastomere membranes, but evidence for EGP binding to sperm
      membranes is equivocal. After in vitro fertilizaton the proportion of sheep
      oocytes cleaving was increased in the presence of oEGP, but when single-cell
      embryos were cultured with oEGP, these cleavage rates were reduced. In addition,
      consistent positive effects of oEGP were observed on blastocyst formation.
      Elaboration of the mechanism of synthesis of EGP, its action and its role in
      fertilization and embryo development is important for our understanding of the
      events of early pregnancy.

PMID- 7623324
TI  - Investigating local regulation of the testes of ruminants.
AB  - In addition to endocrine regulation by the gonadotrophic hormones, the functions
      of the testes are regulated locally by paracrine and autocrine factors. Some
      attempts have been made to isolate cells from the testes of immature bulls and
      rams for investigation of cell function in vitro. However, most studies have used
      in vitro cultures of cells isolated from the testes of rats and a large variety
      of factors have been identified as potential local regulators. This review
      examines the importance of Sertoli cell-germ cell interactions, Leydig cells and
      steroidogenesis, blood flow and vascular permeability, and cytokines and immune
      cells as local regulators of the testes. The small amount of work undertaken on
      the testes of ruminants is reviewed together with approaches such as the
      transilluminated dissection of staged seminiferous tubules and in vivo cell
      depletion models used with rats. The suitability and limitation of these
      approaches for ruminants are considered, and immunological and molecular probes
      are raised as options for future investigations of the local regulation of the
      testes of ruminants.

PMID- 7623325
TI  - Control of antral follicle development and selection in sheep and cattle.
AB  - The development of antral follicles in sheep and cattle is dependent on FSH, but
      large antral follicles can shift their gonadotrophic dependence from FSH to LH.
      The mechanisms that result in the selection of at least one ovulatory follicle
      from identical follicular cohorts, exposed to the same endocrine environment,
      still remain to be elucidated. The aim of this research was to extend in vitro
      results from the rodent to sheep and cattle and, using both in vivo and in vitro
      models, to identify factors that can enhance or attenuate the action of
      gonadotrophins in stimulating follicle development. Using sheep with ovarian
      autotransplants, we have obtained evidence to show that a number of factors
      inhibit ovarian function in vivo, whereas only insulin-like growth factor I (IGF
      I) has a stimulatory effect. Further study of the mechanism of action of these
      factors at a cellular level has been made possible by the development of a serum
      free granulosa cell culture system for both sheep and cattle that allows
      induction and maintenance of oestradiol production. Using this model system, we
      have confirmed many of the results from out studies in vivo and have shown that
      IGF-I and insulin interact at physiological concentrations to influence both
      cellular proliferation and oestradiol production. Overall, these data support the
      hypothesis that the physiological basis of follicle selection is the differential
      expression of factors that modulate the action of gonadotrophins on follicular
      cells at key points during the process of follicle development.

PMID- 7623326
TI  - Immunological manipulation of ovulation rate for twinning in cattle.
AB  - Unlike in sheep, in which immunization against androstenedione causes mild and
      reasonably controlled increased ovulation rate, in similar studies cattle showed
      highly variable responses ranging from increased ovulation rate and fertility
      through to anovulation/anoestrous or superovulation. As a consequence, interest
      in manipulation of ovulation rate through this approach has declined and is now
      focused on immunological manipulation of endogenous inhibin following successful
      studies in sheep. Studies have concentrated on developing a prototype inhibin
      based vaccine to be used for twinning in the Australian beef industry. The
      prototype vaccine (with recombinant ovine inhibin-alpha.3 fusion protein and
      Montanide:Marcol adjuvant) has proved to be very potent and control of the degree
      of ovarian stimulation has not been possible. The proportion of cattle with
      increased ovulation rate after inhibin immunization is affected by timing of
      booster vaccination within the ovarian cycle, time after vaccination, vaccine
      formulation and possibly genotype. Physiological studies show that cattle
      responding to the inhibin vaccine have increased plasma inhibin binding of native
      bovine inhibin, high plasma FSH concentrations, greater numbers of large (> or =
      8 mm) follicles and fewer small (< 5 mm) follicles during the preovulatory wave
      of follicular development compared with control or non-responding animals.
      Significant correlations among the response parameters (i.e. inhibin binding,
      plasma FSH concentrations, number of large follicles and ovulation rate) have
      been demonstrated. The results indicate that greater understanding of the various
      processes of folliculogenesis will be necessary to achieve a controlled increase
      in ovulation rate in cattle.

PMID- 7623327
TI  - Involvement of immune cells in regulation of ovarian function.
AB  - Primary cultures of luteal cells have been used to determine both acute and
      chronic effects of cytokines on luteal cell function and viability. Gonadotrophin
      stimulated progesterone production is inhibited by interleukin 1 beta (IL-1
      beta), tumour necrosis factor alpha (TNF-alpha), or gamma-interferon (IFN-gamma),
      the last two cytokine being more effective than IL-1. In contrast, all three
      cytokines are potent stimulators of prostaglandin production by these cells. The
      mechanism by which prostaglandin synthesis is enhanced may differ slightly for
      each cytokine. In luteal cells, TNF-alpha appears to act primarily through
      stimulation of phospholipase A2, whereas IL-1 beta may activate phospholipase C
      and prostaglandin endoperoxide synthase (PGS) in addition to phospholipase A2.
      The mechanism of action of IFN-gamma has not yet been determined. In addition to
      the observed functional effects, cytokines may also promote cell death during
      luteal regression. Although the three cytokines mentioned have little or no
      effect on viability of cultured luteal cells when administered separately,
      combined treatment with TNF-alpha and IFN-gamma results in a substantial decrease
      in the number of viable cells. Inhibition of cytokine-stimulated prostaglandin
      production does not alter the cytotoxic effect of these cytokines. Expression of
      major histocompatibility (MHC) class I molecules on luteal cells is enhanced, and
      MHC class II molecules are induced, by exposure to IFN-gamma. This is especially
      intriguing, as MHC class II expression increases before luteal regression in
      vivo, and is suppressed in early pregnancy. In summary, evidence is rapidly
      accumulating that supports the hypothesis that the function or structural
      integrity of luteal cells may be modulated by resident immune cells. Future
      research will probably address how these local events are hormonally controlled,
      and if they can be modified to regulate corpus luteum function.

PMID- 7623328
TI  - Dynamics of molecular mechanisms underlying ovarian oxytocin secretion.
AB  - In the ruminant ovary, synthesis and secretion of oxytocin begin in the granulosa
      cells of the preovulatory follicle and are markedly stimulated by the surge of LH
      and FSH. Luteinization of the granulosa cells results in a further increase in
      oxytocin gene expression, but translation of mRNA appears to be retarded because
      the peak concentration of luteal oxytocin occurs later than the maximal
      accumulation of the message. Several hormones have been shown to stimulate
      oxytocin secretion from granulosa and luteal cells in vivo or in vitro. However,
      the role of prostaglandin F2 alpha (PGF2 alpha) in regulating luteal oxytocin
      secretion has perhaps received more study than other hormones. The mechanism of
      action of PGF2 alpha has been shown to encompass a phosphoinositide cascade and
      activation of protein kinase C, events that are associated with luteal secretion
      of oxytocin. Protein kinase C phosphorylation of the actin-binding protein
      myristolated alanine-rich C kinase substrate (MARCKS) may be required for
      exocytosis of oxytocin.

PMID- 7623329
TI  - Cellular interactions during implantation in domestic ruminants.
AB  - Implantation is a critical step in the progress of pregnancy, during which the
      conceptus acquires a fixed position within the uterine lumen, and leads to the
      establishment of the placental structures. This process implies some cellular
      modifications of both the uterine epithelium and the trophoblast to ensure cell
      adhesion between the two tissues. In ruminants, the implantation process is
      characterized by three main steps: a long pre-attachment period lasting 2-3 weeks
      during which the conceptus elongates considerably, an apposition stage when
      cellular contacts are established between the trophoblast and the uterine
      epithelium, and an adhesion stage which ends the process and gives rise to the
      cellular structure of an epithelio-chorial placenta. Trophoblast apposition
      begins in the vicinity of the embryo by day 15, 18 and 19 in sheep, goats and
      cows, respectively. The trophoblast cells surrounding the embryo show
      morphological and functional changes. These modifications are local within the
      conceptus since non-implanted areas of trophoblast still display the
      morphological and functional features that characterized this tissue during the
      pre-attachment period. As the implantation process spreads towards the extremity
      of the elongated conceptus, these cellular transformations progressively affect
      the whole trophoblast. Apposition is completed by a close adhesion between the
      interdigitating uterine microvilli and the trophoblastic plasma membrane. By this
      stage, trophoblastic binucleate cells migrate through the trophoblast monolayer
      and fuse with individual uterine cells to form a syncytial tissue. During this
      process placental lactogen hormones and pregnancy serum proteins (PSP) produced
      by the binucleate cells are transported to the endometrial tissues and then to
      the maternal blood circulation.

PMID- 7623330
TI  - Endocrine basis for puberty in heifers and ewes.
AB  - Maturation processes that culminate in puberty and sexual maturity are initiated
      before birth, continue through prepuberty (> 50 days before puberty) and
      peripuberty (50 days before puberty) and are completed early after puberty. The
      hypothalamus is the primary site of change during transition to sexual maturity.
      Maturation of the hypothalamus results from decreased negative feedback of
      oestradiol that leads to increased frequency of release of LH pulses. Increased
      tonic release of LH pulses during sexual maturation is the primary endocrine
      factor that regulates the onset of puberty in ewe lambs and heifers. Increased
      frequency of release of LH pulses enhances development of ovarian follicles which
      produce enough oestradiol to induce behavioural oestrus and a preovulatory surge
      of gonadotrophins. In later stages of peripuberty, ovulation or luteinization of
      follicles results in transient increases in progesterone for shorter periods than
      is typical for luteal phases of the oestrous cycle of mature ewes and cows.
      Transient increases in progesterone are not generally preceded by behavioural
      oestrus. After the demise of the transient luteal structures, puberty is attained
      with occurrence of the first behavioural oestrus that is accompanied by ovulation
      and development of a corpus luteum with a typical lifespan. At puberty, all
      components of the hypothalamic-pituitary-ovarian axis are in place for oestrous
      cycles to be expressed. Factors that can influence the pubertal rise in release
      of LH pulses are genotype, gender, season of year when pubertal age is attained,
      growth or nutritional intake, social cues or treatment with exogenous progestins.
      Sexual maturation continues after puberty with an enhanced probability of
      pregnancy occurring from actions of ovarian steroids at the uterus.

PMID- 7623331
TI  - Involvement of thyroid hormones in seasonal reproduction.
AB  - This article reviews experiments performed to investigate the importance of
      thyroid hormones to the expression of the seasonal reproductive cycle of ewes.
      Thyroidectomy was found to block the transition from the breeding season to
      anoestrus and to cause ewes to exhibit oestrous cycles all year round.
      Mechanistically, thyroidectomy produced this effect by preventing the seasonal
      increase in responsiveness to the negative feedback action of oestradiol on
      episodic GnRH secretion, thus interfering with a key neuroendocrine process
      necessary for anoestrus to develop. This response to thyroidectomy was fully
      prevented by replacement with physiological concentrations of thyroxine.
      Furthermore, the reproductive response to thyroidectomy was specific to the
      mechanisms that lead to anoestrus; other aspects of reproductive neuroendocrine
      function and seasonal and photoperiodic mechanisms were not affected. Evidence is
      presented to indicate that thyroid hormones have a permissive mode of action on
      seasonal reproduction, and that their effect is exerted during a restricted
      'window' of time during the year. It is concluded that thyroid hormones play a
      crucial role of physiological significance to generation of the seasonal
      reproductive cycle of ewes.

PMID- 7623332
TI  - Melatonin binding sites and their role in seasonal reproduction.
AB  - The pineal gland has a major role in the translation of scotophase duration into
      a hormonal signal by the hormone melatonin. Animals such as sheep, goats and deer
      use the seasonal variation of this signal to coordinate reproductive behaviour
      with the environment. Despite intensive research over more than 30 years the
      site(s) of action of melatonin and the resultant intracellular responses are
      still not clear. This review discusses recent work that has localized the site of
      action of melatonin in sheep using administration into the hypothalamus in vivo
      as well as studies on putative melatonin receptors in the pars tuberalis and
      brain. There is clear evidence that melatonin acting at the level of the pars
      tuberalis is involved in the seasonal regulation of prolactin secretion, but the
      evidence for involvement of the pars tuberalis in seasonal reproduction is not
      compelling. Localized administration of melatonin to the sheep brain revealed
      that areas anatomically distinct from the pars tuberalis, the ventromedial and
      arcuate nuclei, simulated seasonal reproductive changes in rams and ewes. Recent
      studies on brain melatonin binding sites in our laboratory have shown that an
      antagonist of tissue transglutaminase, Bacitracin, as well as substrates for the
      enzyme inhibit binding of melatonin to brain membranes. As a working hypothesis,
      we propose that pineal melatonin secretion alters seasonal reproduction by
      interactions with a neural transglutaminase at the synapse of neurones involved
      in the control of GnRH secretion. Synaptic transglutaminase is implicated in the
      control of the release of neurotransmitter via the synaptic vesicle associated
      protein, synapsin 1; activation of transglutaminase results in the covalent
      modification of synapsin 1 such that vesicles are not released from the
      cytoskeleton. Seasonal variation in the duration of melatonin secretion may
      result in similar variations in the duration of suppression and activation of
      transglutaminase. The resultant changes in transmitter release may then be
      responsible for the seasonal neuronal plasticity previously observed in GnRH
      neurones.

PMID- 7623333
TI  - Nutritional influences on reproduction in mature male sheep and goats.
AB  - Changes in the nutrition of mature rams and goat bucks lead to profound responses
      in testicular size and therefore the rate of production of spermatozoa. These
      effects are largely due to changes in the size of the seminiferous tubules and in
      the efficiency of spermatogenesis. With the exception of severe undernutrition,
      the effects on spermatogenic function are not accompanied by similar changes in
      endocrine function of the testes, as measured by the production of testosterone
      or inhibin. In rams, moderate changes in nutrition affect gonadotrophin secretion
      for only a few weeks, whereas testicular growth is affected for several months.
      In mature male goats during the non-breeding season, nutrition-induced testicular
      growth does not seem to be associated with a gonadotrophin response. Such
      observations have led us to develop the hypothesis that nutrition-driven
      testicular growth is at least partly independent of changes in gonadotrophin
      secretion. The energetic components of the diet, rather than the protein content,
      seem to be responsible for affecting gonadotrophin secretion in rams. The
      volatile fatty acids, and not glucose, are the active factors, although
      intracerebral insulin may also play a role. Where these substrates act and
      whether they are also involved in the gonadotrophin-independent pathways requires
      testing. In conclusion, nutritional signals exert powerful effects on the
      reproductive system of mature male ruminants, and the responses are partly
      independent of changes in gonadotrophin secretion. In the gonads, the gametogenic
      tissue responds rapidly to changes in nutrition, but the endocrine compartments
      are less affected. Variations in the expression of the nutritional responses
      among sexes, breeds and species probably reflect variations in the role of this
      environmental factor as a modulator of reproductive function.

PMID- 7623334
TI  - Stress and reproduction in farm animals.
AB  - Transport of post-partum cows or sheep before an oestradiol-induced LH surge
      delayed gonadotrophin secretion possibly by affecting hypothalamic activity but
      not via an opioid mediated mechanism as the effect could not be reversed by
      naloxone. In addition, reduced LH responses to GnRH were observed in cattle
      during transport. In sheep, adrenocorticotrophic hormone (ACTH) also diminished
      the LH response to GnRH, but only when GnRH was administered 3 h after ACTH, not
      after 0.5 h. This finding suggests that very early suppression of LH secretion by
      stressors is not mediated by ACTH action at the pituitary but that immediate
      activation of the sympathetic nervous system may be involved. In ewes during the
      breeding season, repeated exposure to GnRH at intervals of 2 h during transport
      resulted in lower LH responses to the second and third injections. When
      anoestrous ewes were treated with oestradiol and GnRH while being restrained and
      isolated, the onset of the LH surge was delayed. The effects of hypothalamus
      pituitary-adrenal hyperactivity on LH release may involve suppression of GnRH
      receptor activity, a reduction in releasable LH, or both factors. Studies in
      vitro with perifused ovine pituitaries showed that ACTH or corticotrophin
      releasing hormone markedly suppressed LH secretion in response to the second of
      two exposures to GnRH. This occurred with pituitaries obtained from anoestrous
      ewes irrespective of prior treatment with oestradiol, suggesting that compounds
      from the hypothalamus-pituitary-adrenal do not exert effects on the oestradiol
      sensitizing mechanisms on the pituitary. In conclusion, stressors affect
      reproductive function via actions at the hypothalamus as well as impairing
      pituitary LH release induced by GnRH.

PMID- 7623335
TI  - Sensory and behavioural control of gonadotrophin secretion during suckling
      mediated anovulation in cows.
AB  - A major limiting factor in the resumption of postpartum ovarian cycles in cattle
      is the inhibitory influence of the suckling calf on central regulatory elements
      controlling the release of GnRH from the median eminence. This inhibitory
      influence occurs only as a consequence of specifically defined behavioural
      interactions between the cow and calf in the presence of a maternal bond, cannot
      be simulated experimentally using thermal, electrical or mechanical stimuli, and
      is not dependent upon sensory ennervation within the udder. Indeed, the identity
      of the calf, either own or unrelated, appears to define the neuroendocrine events
      that attend the maintenance of the anovulatory state under controlled
      experimental conditions. Hence, new hypotheses that focus upon the relationship
      between physiological correlates of maternal behaviour and hypothalamic
      regulation of LH secretion are currently being tested. Specific aspects of these
      relationships remain conjectural, but are postulated to include the regulation of
      opioid tone, intracerebral oxytocin, and modulation of synthetic or excitatory
      activity of GnRH secretory neurones. Defining the role of the special senses in
      transduction of signals from calves that influence these neuronal processes may
      provide insight for developing practical intervention strategies of the future.

PMID- 7623336
TI  - Physiological effects of undernutrition on postpartum anoestrus in cows.
AB  - The focus of this review is the physiological effects of undernutrition on
      ovarian follicle growth and the occurrence of ovulation in postpartum cows.
      Evidence suggests that moderate levels of underfeeding, before or after calving,
      may interfere with the mechanism(s) of final follicle maturation and ovulation,
      whereas more pronounced nutritional deficiencies may affect the mechanism(s)
      regulating dominant follicle size and the dynamics of dominant follicle growth
      and regression. Severe undernutrition may result in the absence of follicles > 5
      mm in diameter. These changes are consistent with likely effects of reduced LH or
      FSH secretion that have been associated with inhibition of both tonic and surge
      release of GnRH from the hypothalamus. As yet, there is no direct evidence for
      local effects of undernutrition on ovarian function in cows, and studies
      examining this tissue often ignore dynamic interdependencies between the
      hypothalamus, anterior pituitary gland, and the ovaries, and possible nutritional
      modulation of ovarian feedback mechanisms that affect gonadotrophin secretion.
      Further research is required to elucidate nutritional effects on the positive
      feedback regulation of gonadotrophin secretion and on the expression of
      behavioural oestrus. Further studies are also needed to determine whether
      nutritional or metabolic state may influence ovarian function directly in a
      manner that affects the duration of postpartum anoestrus and fertility in
      postpartum cows.

PMID- 7623338
TI  - Plasma concentrations of dimeric inhibin and oestradiol in heifers undergoing
      superovulation with eCG or FSH.

PMID- 7623339
TI  - Generation of monoclonal antibody to ovine FSH and its application in
      immunoneutralization and enzymeimmunoassay.

PMID- 7623337
TI  - Factors that affect fertility during oestrous cycles with short or normal luteal
      phases in postpartum cows.
AB  - We have used a model to study infertility in postpartum cows. In mated cows with
      short luteal phases, daily supplementation with progestagen, beginning on day 3,
      failed to maintain pregnancy, despite the fact that fertilization, early embryo
      development and transport of the embryo into the uterus appeared to be normal.
      Normal embryos were transferred, on day 7 after oestrus, into cows with short
      luteal phases that received daily supplementation with progestagen, and embryos
      from cows with short luteal phases were transferred, on day 6 after mating, into
      cows with normal cycles. Pregnancy rates in each case were about half those
      achieved using progestagen-pretreated cows with normal luteal phases. In mated
      cows with short luteal phases supplemented with progestagen, pregnancy rates were
      markedly improved by removal of the regressing corpus luteum on day 4 or 5 after
      mating. In cows with normal cycles, fertility was lower when preovulatory
      concentrations of oestradiol were high for more than 3 days. This may result from
      persistent follicles, which develop when progesterone is low and frequency of
      tonic pulses of LH is high. In cows with such follicles, oocytes may resume
      maturation before the surge of LH, and embryos died in the oviduct before the 16
      cell stage. Finally, in both early postpartum cows with transferred embryos and
      cows with normal cycles, excessive follicular development and high oestradiol
      during the luteal phase were detrimental to embryo survival. Treatments designed
      to maximize fertility in early postpartum cows must provide high progesterone and
      low oestradiol before mating and not yield luteolytic influences such as PGF2
      alpha and oestradiol, both early after mating and during maternal recognition of
      pregnancy.

PMID- 7623340
TI  - Identification and localization of collagen types I and IV in the ruminant
      follicle and corpus luteum.

PMID- 7623342
TI  - Effects of gonadotrophin concentration on hormone production by theca interna and
      granulosa cells from bovine preovulatory follicles.

PMID- 7623341
TI  - Pulsatile hormone secretion during the first ovarian follicular wave in Bos
      indicus heifers.

PMID- 7623343
TI  - The oxytocin receptor, luteolysis and the maintenance of pregnancy.
AB  - During luteal regression episodic pulses of oxytocin secretion become coupled to
      the release of prostaglandin F2 alpha (PGF2 alpha) following synthesis of
      endometrial oxytocin receptors, but in early pregnancy the inhibition of oxytocin
      receptor formation by the conceptus prevents the development of the pulsatile
      pattern of PGF2 alpha release needed to achieve luteolysis. Oxytocin receptors
      are present on the luminal epithelium in ovariectomized and anoestrous ewes, in
      pregnant animals throughout most of gestation (day 21 to term) and in explants of
      endometrial tissue cultured in vitro. These receptors can be downregulated for a
      brief period by progesterone (10-12 days in sheep, 12-14 days in cattle). This
      period of inhibition can be extended by infusion of interferon tau (IFN-tau)
      (which probably inhibits oxytocin receptor gene transcription) or of oxytocin
      into the systemic circulation (which may act further downstream, possibly at the
      level of translation). Oxytocin receptors also develop on the caruncular stroma
      and deep glands at oestrus, but these need positive upregulation and appear
      dependent on an oestrogenic environment. Only epithelial receptors are needed to
      achieve a maximal PGF2 alpha response to an oxytocin challenge, but the presence
      of oxytocin receptors does not necessarily confer responsiveness as other factors
      may influence intracellular coupling mechanisms and precursor availability. The
      duration of the luteal phase is regulated by the time of the initial post
      ovulatory rise in progesterone and the duration of exposure to
      progesterone.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7623345
TI  - Evidence for dopamine D1 receptor-mediated stimulation of prolactin secretion in
      ewes under long daylength.

PMID- 7623344
TI  - Effect of suppression of pituitary-testicular function during fetal life with a
      GnRH agonist on reproductive development in ram lambs during the first 28 weeks
      of life.

PMID- 7623346
TI  - The ovarian follicular wave pattern in the mated and non-mated dromedary camel
      (Camelus dromedarius).

PMID- 7623347
TI  - Electrofusion of in vitro produced bovine embryonic cells for the production of
      isofusion contours for cells used in nuclear transfer.

PMID- 7623348
TI  - Prostaglandins and the maintenance of pregnancy in goats.

PMID- 7623349
TI  - A dual role for progesterone in the control of cyclicity in ruminants.

PMID- 7623350
TI  - Interactions between the immune system and the ruminant conceptus.
AB  - Interactions of the conceptus with the immune system can involve either anti
      sperm or anti-conceptus immune responses that limit the success of pregnancy of
      beneficial effects of cytokines released from lymphoid cells on embryonic growth
      and gene expression. The immune system is functional in the uterus and therefore
      there is the potential for anti-conceptus immune responses. However, endometrial
      lymphocytes are distinct in many respects from lymphoid cells at peripheral
      sites; one major subpopulation expresses the gamma delta T-cell receptor and may
      not recognize major histocompatibility antigens. There are also several control
      systems to limit anti-conceptus immune responses. In particular, expression of
      major histocompatibility antigens on the trophoblast is either absent or of
      limited distribution. In addition, activation of anti-conceptus immune responses
      leading to cytolytic responses is further limited by the presence of molecules
      that can inhibit lymphocyte transformation. The most well-characterized of these
      are prostaglandin E2 from placental and endometrial tissues, interferon-tau from
      the trophoblast during early pregnancy, and two endometrial proteins called the
      uterine milk proteins (UTMP). Progesterone plays a central role in inhibition of
      immune responses in actions that are mediated at least in part through
      endometrial secretion of UTMP. Cytokines play important roles as autocrine and
      paracrine regulators in many tissues including the reproductive tract. In
      ruminants, the best described example is interferon-tau. Other cytokines found in
      the reproductive tract or produced by the conceptus include interleukin-1,
      leukaemia inhibitory factor, granulocyte-macrophage colony stimulating factor and
      interleukin-6. It is possible that the major source of cytokines in the
      reproductive tract is non-lymphoid cells of the endometrium and trophoblast. It
      is not known to what extent endometrial lymphocytes contribute to the cytokine
      milieu because no cytokine has been identified as a product of endometrial
      lymphocytes. However, there is a population of granulated lymphocytes that
      increase in number and granularity in the luminal epithelium of the late-pregnant
      ewe that is a potential source of cytokines.

PMID- 7623351
TI  - The growth hormone/prolactin gene family in ruminant placentae.
AB  - Ruminant placentae produce at least two distinct subclasses of the growth
      hormone/prolactin gene family, the placental lactogens and prolactin-related
      proteins. Placental lactogens have been purified from cattle, goat and sheep
      placentae, and the amino acid sequences of bovine and ovine placental lactogen
      are known. Bovine and ovine placental lactogens are structurally more similar to
      prolactin than they are to growth hormone. In addition, six unique mRNAs have
      been described in cattle that encode prolactin-related proteins that are
      structurally distinct from ruminant placental lactogens. All characterized
      ruminant placental lactogens and prolactin-related proteins are products of
      chorionic binucleate cells, but specific biological functions of these placental
      hormones have not been elucidated. Ovine placental lactogen may modify maternal
      and fetal intermediary metabolism to provide energy substrates to the fetus.
      Bovine placental lactogen has been implicated as a luteotropic agent, and is also
      capable of stimulating mammogenesis and lactogenesis. No ruminant placental
      lactogen receptor has been structurally characterized, although they are presumed
      to be similar to either the growth hormone or prolactin receptor. Available
      technologies will allow many of the questions regarding the regulation, mechanism
      of action and function of these placental hormones to be addressed.

PMID- 7623352
TI  - Structural and functional properties of the corpus luteum of pregnancy.
AB  - In domestic ruminants the parenchyma of the corpus luteum consists of two
      subpopulations of steroidogenic cells commonly referred to as small and large
      luteal cells. These cells differ not only in size and structural characteristics,
      but also in functional properties. During the mid-luteal phase of the oestrous
      cycle approximately 60% of the corpus luteum is occupied by steroidogenic cells.
      Although the steroidogenic capacity of these cells declines as pregnancy
      advances, the cells persist as distinct populations throughout pregnancy and for
      several days following parturition. In general, structural changes typically
      observed at the end of the oestrous cycle also occur after parturition, but over
      a more extended period. These include deletion of endothelial cells and occlusion
      of capillary lumina with cellular debris and apoptotic bodies, an infiltration of
      eosinophils and macrophages, and fragmentation and lysis of parenchymal cells.
      However, not all parenchymal cells undergo lysis, nor are they rapidly
      phagocytosed by macrophages. Instead, many fuse to form what appear to be large
      syncytia that contain numerous lipid droplets, tightly packed mitochondria and
      multiple nuclei with condensed chromatin. Fusion of parenchymal cells to form
      syncytial profiles begins 2-3 days after parturition and the syncytia persist for
      at least 22 days post partum. By day 35 post partum transformation of the corpus
      luteum into a corpus albicans is essentially complete.

PMID- 7623353
TI  - Differentiating lymphocytic adenohypophysitis from pituitary adenoma in the
      peripartum patient.
AB  - Lymphocytic adenohypophysitis (LAH) is an autoimmune disorder of the pituitary
      gland with a predilection for the peripartum period and often mimics a pituitary
      adenoma. We sought to define the clinical, endocrinologic and radiographic
      characteristics differentiating peripartum LAH from pituitary adenoma to enable
      the use of noninvasive diagnosis and appropriate therapy. From published reports
      and our own case, the clinical histories and laboratory and radiographic studies
      of 45 patients fulfilling the diagnosis of peripartum LAH were reviewed. History
      of infertility or menstrual irregularity, symptomatology, endocrinologic
      evaluation, diagnostic imaging and associated medical conditions were analyzed.
      For comparison, 806 patients with pituitary adenoma and pregnancy from published
      series were evaluated. The spontaneous pregnancy rate in pituitary adenoma
      patients was 2.4% vs. 100% in LAH patients. Visual disturbances and headaches
      were significantly more frequent in patients with LAH. Prolactin levels were
      significantly lower in patients with LAH than in those with pituitary adenomas
      (34.6 +/- 46.3 [SD] vs. 393.0 +/- 300.4, P < .0001). Abnormalities in thyroid
      and/or adrenal function were also more common in patients with LAH (57.5% vs.
      2.5%, P < .001). There were no distinguishing characteristics on radiographic
      studies. History and endocrinologic evaluation can differentiate between LAH and
      pituitary adenoma in the peripartum patient.

PMID- 7623355
TI  - Hormone replacement therapy and atherosclerosis.
AB  - Atherosclerotic changes associated with long-term hormone replacement therapy
      (HRT) were evaluated in 20 postmenopausal women (mean age, 62.8 +/- 6.1 years).
      The duration of hormone therapy was 10.1 +/- 3.4 (SD) years. For 9 women the HRT
      was sequential estradiol valerate plus levonorgestrel, for 6 women estradiol
      valerate plus medroxyprogesterone acetate and for 5 women estradiol valerate
      alone. Examinations consisted of histologic and biochemical studies of the
      uterine artery and ultrasonographic examinations of carotid arteries, aorta and
      iliac arteries. The findings were compared with those in 20 postmenopausal women
      of similar age and with similar body mass indexes who had never received HRT.
      Additionally, the same examinations were performed on 10 premenopausal women
      (48.3 +/- 4.6 years). The uterine artery was histologically normal in all the
      premenopausal women studied. Among the postmenopausal women without HRT, a
      histologically normal uterine artery was found in 5% and in women on HRT in 55%
      of cases (P < .01). In medicolegal autopsies, atherosclerosis in the uterine
      artery correlated significantly with atherosclerosis in the coronary artery and
      aorta. The free cholesterol content of the intima media in premenopausal women
      was lower than in postmenopausal women without HRT. The percentage of linoleic
      acid in the intima was significantly lower and that of docosapentaenoic acid
      significantly higher in premenopausal women and in postmenopausal women on HRT
      than in postmenopausal women without HRT. In the ultrasonographic examination
      atherosclerosis in the carotid artery was less common in premenopausal women and
      in women on HRT than in postmenopausal women without HRT. In this material,
      histologic, biochemical and radiologic studies showed that HRT may be protective
      against atherosclerosis.

PMID- 7623354
TI  - Evaluation of lamellar body number density as the initial assessment in a fetal
      lung maturity test cascade.
AB  - The objective of this study was to assess the sensitivity and specificity of
      lamellar body number density in the prenatal prediction of the respiratory
      distress syndrome. Seventy consecutive amniotic fluid specimens obtained by
      amniocentesis within 72 hours of delivery were assessed for lamellar body number
      density, optical absorbance at 650 nm, lecithin/sphingomyelin ratio and
      phosphatidylglycerol. A maturity criterion of > or = 46,000/microL for lamellar
      body number density yielded values for diagnostic sensitivity of 100% (7/7),
      specificity of 89% (49/55), positive predictive value of 54% (7/13) and negative
      predictive value of 100% (49/49). These values were also determined for the other
      analytes, with results similar to those reported elsewhere. Lamellar body number
      density is an effective and inexpensive first test for the rapid identification
      of the fetus at high risk for the respiratory distress syndrome. A cascade
      approach, using lamellar body number density as the first test and optical
      absorbance at 650 nm as the second test, improves the predictive value as
      compared to any single test of fetal lung maturity.

PMID- 7623356
TI  - Laparoscopically directed ovarian cystectomy in premenopausal women. Impact of
      surgical experience on surgical time.
AB  - The purpose of this study was to correlate surgical experience with operating
      efficiency. A retrospective review of 303 operative laparoscopic procedures was
      performed during a 48-month interval and during the acquisition of surgical
      skills by one faculty member. Population demographics and surgery time were
      evaluated in 41 cases (13.5%) of ovarian cystectomy. Patients were categorized
      into fertility-related or gynecologic indications for surgery. Surgical time for
      successful laparoscopically directed resection of benign ovarian cysts was
      significantly reduced over the study interval (P = .008). Endometrioma was the
      most common pathologic finding in women with impaired fertility, and benign
      epithelial tumors were the lesion encountered most commonly in gynecologic
      patients. Benign teratoma occurred infrequently in both groups. No malignancy was
      observed in this group of premenopausal women, who had unilocular cysts less than
      8 cm in diameter. Reduction in surgical time for laparoscopically directed
      ovarian cystectomy occurs after experience is gained by repeated application of
      the technique.

PMID- 7623357
TI  - Effect of vitamin E on adhesion formation.
AB  - This study investigated the effects of vitamin E on adhesion formation and
      fibrosis. Forty-eight adult, virgin, female Sprague-Dawley rats were divided
      equally into two groups, one of which received 300 mIU/kg vitamin E orally in
      their daily diet in comparison with the control group, which received the vehicle
      only. Laparotomy was performed and the uterine horns identified. Denuding of the
      serosa was performed over a segment of the right horn; bipolar coagulation over a
      similar area on the left horn was performed. Following the procedure the animals
      continued on the same diet for three weeks. They were then killed, the adhesions
      were graded, and microscopic evaluation for fibrosis was accomplished. Although
      there was a trend of less fibrosis with vitamin E, there was no statistically
      significant difference, nor was there a difference with respect to a reduction in
      adhesion formation.

PMID- 7623358
TI  - Treatment of vulvar vestibulitis syndrome with electromyographic biofeedback of
      pelvic floor musculature.
AB  - Thirty-three women diagnosed as suffering from vulvar vestibulitis syndrome,
      marked by a significant history of long-term moderate to severe chronic introital
      dyspareunia and tenderness of the vulvar vestibule, were selected for treatment.
      Patients were given a computerized electromyographic evaluation of the pelvic
      floor muscles and were then provided with portable electromyographic biofeedback
      instrumentation and instructions on the conduct of daily, at-home, biofeedback
      assisted pelvic floor muscle rehabilitation exercises. They received intermittent
      evaluations of pelvic floor muscles to ensure compliance and monitor their
      progress and symptom changes. The results show that after an average of 16 weeks
      of practice, pelvic floor muscle contractions increased 95.4%, resting tension
      levels decreased 68%, and the instability of the muscle at rest decreased by 62%.
      Subjective reports of pain decreased an average of 83%. Twenty-eight patients had
      abstained from intercourse for an average of 13 months. Twenty-two of these 28
      patients resumed intercourse by the end of the treatment period. Six month follow
      up indicated maintenance of therapeutic benefits.

PMID- 7623359
TI  - Human papillomavirus infections in vulvar precancerous lesions and cancer.
AB  - To elucidate some of the recently arisen issues related to the bimodal disease
      pattern of vulvar intraepithelial lesions (VIN) and vulvar cancer, a series of 27
      consecutive women with vulvar symptoms was analyzed for human papillomavirus
      (HPV) involvement by colposcopy, light microscopy and in situ hybridization (ISH)
      for HPV types 6, 11, 16, 18, 31, 33 and 42. Altogether, HPV DNA was discovered in
      13/27 (48.1%) of the lesions by ISH; the rest were HPV DNA negative for the seven
      HPV types tested. HPV DNA was present in both of two exophytic lesions (HPV 6 in
      condyloma and HPV 16 in verrucous cancer). Of the flat lesions, 7/13 (53.8%) were
      HPV DNA positive. HPV 6 was confined to low grade lesions (HPV/non-VIN and VIN
      1), whereas HPV 11 was found in a case of VIN 3 as well. Of the invasive
      carcinomas, three of four were HPV DNA positive (2 HPV 16 and 1 HPV 31).
      Dystrophic changes were detected in three of four invasive carcinomas and in all
      three HPV 16-positive lesions. Dystrophic changes were absent in 9 of 14 (64.3%)
      of HPV DNA-negative lesions. Fifty percent (7/14) of vulvar warty lesions
      (without concomitant VIN) were found in women younger than 60. Three of four
      invasive carcinomas occurred in women older than 60. This small series provided
      additional evidence of HPV involvement in the pathogenesis of VIN lesions, and
      the findings support the hypothesis of a multifactorial etiology in vulvar
      carcinogenesis in which HPV, dystrophic changes and chronic inflammatory disease
      play a synergistic role.

PMID- 7623360
TI  - Manchester procedure vs. vaginal hysterectomy for uterine prolapse. A comparison.
AB  - The Manchester procedure (MP) was compared with vaginal hysterectomy (VH) to
      determine whether any differences regarding patient demographics or operative or
      postoperative outcome could be found between the two techniques. A retrospective
      chart analysis was done comparing data from 88 consecutive MP to 105 randomly
      selected VH patients. All the operations were performed for uterine prolapse at
      Mount Sinai Hospital between 1984 and 1988. MP patients, when compared to VH
      patients, were more likely to be older and postmenopausal at the time of surgery
      and to have a private physician. MP patients were less likely to have significant
      medical illnesses than were VH patients. Statistically significant differences
      between MP and VH were found for operative time (100 vs 130 minutes,
      respectively) and blood loss (200 vs. 300 mL, respectively) (P < .001). This
      difference was not dependent on the performance of anterior or posterior repair.
      MP was associated with shorter operative time and less blood loss when compared
      to VH. This, coupled with apparently similar operative outcomes, suggests the use
      of MP as an alternative to VH in the absence of uterine pathology in appropriate
      candidates with uterine prolapse. Prospective, controlled, long-term studies
      comparing the operative results of these two procedures are needed.

PMID- 7623361
TI  - Postmenopausal hormone replacement therapy with low-dose medroxyprogesterone
      acetate. Endometrium, plasma lipids, lipoproteins and apolipoproteins.
AB  - Several studies have demonstrated that the use of estrogens in postmenopausal
      women has a protective effect against cardiovascular disease; however, this
      beneficial effect may be counteracted when concomitant progestogens are
      administered. We investigated the influence of hormone replacement therapy (HRT)
      with lower doses of medroxyprogesterone acetate (MPA) (2.5 mg/d) on the
      endometrium and on the plasma levels of lipids, lipoproteins and apolipoproteins.
      All the studied HRT regimens induced favorable changes in the levels of plasma
      lipids, lipoproteins and apolipoproteins, which may play an important role in the
      prevention of cardiovascular disease. The dosage of 2.5 mg/d of MPA is clearly
      inadequate to protect the endometrium from hyperplastic changes with sequential
      regimens, but probably this dosage is safe when MPA is administered continuously.

PMID- 7623362
TI  - Polycystic ovary disease. A risk factor for gestational diabetes?
AB  - We investigated the impact of pregestationally elevated insulin plasma levels on
      glycemic control in pregnant women with polycystic ovary disease (PCOD). Twelve
      patients with PCOD who became pregnant within six months following evaluation of
      their metabolic status were the study subjects. Four were obese and six (two
      obese) had a hyperinsulinemic response to the oral glucose tolerance test (OGTT).
      They were tested with the OGTT at 28-30 weeks of gestation. We also tested 12
      normal patients and 10 consecutive patients with gestational diabetes; all were
      at the same gestational age. Plasma levels of insulin and glucose were determined
      in the samples collected for a period of four hours after glucose load (100 g).
      All PCOD patients significantly increased their insulin secretion in pregnancy.
      The hyperinsulinemic PCOD patients developed gestational diabetes (two patients)
      and impaired gestational glucose tolerance (three patients). The area under the
      insulin curve was greater in PCOD patients than in control and gestational
      diabetes patients (P < .01). In spite of their large increase in insulin
      secretion observed during pregnancy, patients with PCOD may develop a derangement
      of glycemic control, probably related to their pregestational insulinemic status.

PMID- 7623364
TI  - Fetal pulmonary sequestration presenting as unilateral idiopathic hydrothorax. A
      case report.

PMID- 7623363
TI  - Noncanalization of the fallopian tube. A case report.
AB  - Anomalous development of the fallopian tubes is an uncommon occurrence, and only
      a few types of structural changes have been described. A woman with a unicornuate
      uterus and noncanalized contralateral fallopian tube with absence of the proximal
      segment is described. This condition has not been reported previously.

PMID- 7623365
TI  - Histiocytosis X of the vulva with a confusing clinical and pathologic
      presentation. A case report.
AB  - Histiocytosis X (HX) is a rare disorder of Langerhans cells and most commonly
      occurs in children. We report a case of HX of the vulva in a 76-year-old woman
      that clinically simulated a yeast infection of the vulva but histologically
      resembled an amelanotic melanoma. We briefly report the clinical and pathologic
      features of this case, which responded to vincristine followed by vinblastine and
      was in complete remission after nine months.

PMID- 7623366
TI  - Improved neonatal outcome of vasa previa with aggressive intrapartum management.
      A report of two cases.
AB  - Two cases of vasa previa ended with neonatal survival as a result of aggressive
      intrapartum management. The etiology and pathophysiology of vasa previa are
      reviewed. The current status of prospective diagnosis is presented, as are the
      essentials of successful neonatal management of this condition.

PMID- 7623367
TI  - Poisoning with antihypertensive drugs: diuretics and potassium supplements.
AB  - Diuretics are widely prescribed to treat hypertension and oedema. The increasing
      use of these drugs opens the possibility of an increase in deliberate or
      accidental self-poisoning. However, experience with overdosage and toxicity with
      the diuretics remains very limited. In general, supportive therapy by the
      reduction of gastrointestinal absorption, monitoring of vital signs and the
      correction of hypertension and electrolyte abnormalities are indicated.

PMID- 7623368
TI  - Low-level lead exposure and blood pressure.
AB  - The possible association between low-level lead exposure and blood pressure (BP)
      remains debated. The purpose of this review was: (1) to determine whether the
      available studies in humans support a positive association, in particular at
      lower exposure levels (blood lead concentration < 1 mumol/l), and (2) to explore
      whether animal studies and the proposed pathophysiological mechanisms are
      supportive of a positive and causal association between lead exposure and
      hypertension. A meta-analysis of 23 studies included 33,141 subjects recruited
      from the general population in 13 surveys and from occupational groups in 10
      studies. In all but four studies the results had been adjusted for age, and most
      studies also considered additional confounders. The association between BP and
      blood lead was similar in both sexes. In all 23 studies combined, a two-fold
      increase in blood lead concentration was associated with a 1 mm Hg rise in the
      systolic pressure (CI 0.4-1.6 mm Hg; P = 0.002) and with a 0.6 mm Hg increase in
      the diastolic pressure (CI 0.2-1.0 mm Hg; P = 0.02). Of 21 animal studies, one
      was carried out in dogs, one in pigeons and the remainder in various rat strains.
      In 15 studies, in which the lead dose in drinking water or food exceeded 1 p.p.m.
      the association between BP and exposure was found to be positive in seven,
      inconsistent in three, absent in four and negative in one. Of the six studies at
      lower exposure levels (< or = 1 p.p.m.), five found a pressor effect attributable
      to lead. Whether the lead doses in the animal studies are equivalent to the human
      exposure levels and to what extent one can extrapolate from genetically
      heterogeneous animals to humans, remains doubtful. If a causal relation between
      lead exposure and hypertension exists, the proposed mechanisms may include
      interference of lead with ion transport across cell membranes, interactions with
      calcium homeostasis and calcium-mediated processes, direct vasomotor actions and
      the potentiation of sympathetic stimulation. Interference of lead with the
      balance between the renin-angiotensin-aldosterone and the kallikrein-kinin
      systems and impairment of renal function are unlikely to be implicated. On
      balance, the published evidence suggests that there can only be a weak positive
      association between BP and lead exposure. The latter relation, which is barely
      visible at the horizon of epidemiological observation, may not be causal in
      nature and is unlikely to entail any public health implication in terms of
      hypertension-related complications.

PMID- 7623369
TI  - Diurnal blood pressure variability in essential hypertension and vascular
      reactivity to isometric stress.
AB  - The present study was designed to assess the hemodynamic conditions, by means of
      impedance cardiography methods, and the relation existing between vascular
      reactivity to isometric stress (isometric handgrip test) and the day/night blood
      pressure variations, estimated by ABPM. Fifty unselected untreated non-obese EEH
      adult subjects (WHO class I) with a duration of disease not exceeding 3 years
      were classified as dippers or non-dippers according to commonly accepted
      criteria. Twenty three normotensive volunteers acted as controls. SBP, DBP, HR,
      CI and SVRI were assessed at rest and after IHG test. At rest dippers, non
      dippers and controls showed comparable CI. SVRI were more enhanced in EEH than in
      controls and, although not significantly, in non-dippers than in dippers. During
      IHG all subjects showed a significant rise of SBP, DBP and HR; CI variations were
      of comparable size in all groups while SVRI increases were not. Non-dippers
      showed a significant SVRI rise after IHG in comparison with resting values. In
      dippers and in controls SVRI increment was insignificantly different in
      comparison with resting values. Non-dippers showed a closest correlation between
      BP and SVRI rise during IHG while dippers showed a less consistent association.
      In conclusion, our data suggest that in adults with short duration EEH the
      existence of non-dipper condition may be unrelated to myocardial hypertrophy.
      Blunted nocturnal BP fall is associated with vascular hyper-reactivity revealed
      by a bigger elevation of SVRI during IHG.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7623370
TI  - Does the Hawksley random zero sphygmomanometer underestimate blood pressure, and
      by how much?
AB  - The study objective was to compare blood pressure (BP) measurement by the
      Hawksley random-zero sphygmomanometer and the standard mercury sphygmomanometer.
      Comparison of simultaneous 'blind' BP measurements were made using the Hawksley
      random-zero sphygmomanometer and the standard mercury sphygmomanometer linked by
      a Y-connector to a single cuff, in the general practice and office environments.
      Sixty five healthy volunteers and general practice patients, aged between 20 and
      50 years (SBP range 82-184 mm Hg, DBP range 38-112 mm Hg), were studied. Each had
      three blood pressure measurements taken. Mean BPs recorded by the Hawksley random
      zero sphygmomanometer were lower than those recorded by the standard mercury
      sphygmomanometer. The Hawksley random-zero sphygmomanometer underestimated SBP by
      1.3 mm Hg (95% CI 0.9-1.8 mm Hg) and DBP by 1.7 mm Hg (95% CI 1.1-2.3 mm Hg).
      These differences between instruments were independent of BP level both for
      systolic and diastolic measurements. An overview including this study and six
      other published reports describing nine studies examining the performance of the
      Hawksley random-zero sphygmomanometer suggested a similar degree of
      underestimation for SBP (mean difference 1.35 mm Hg, 95% CI 1.24-1.46 mm Hg).
      Underestimation of DBP appeared greater (mean difference 2.54 mm Hg, 95% CI 2.43
      2.65 mm Hg) but was reduced when two outlying studies were removed from analysis
      (mean 1.97, 95% CI 1.85-2.09 mm Hg). We conclude that the Hawksley random-zero
      sphygmomanometer underestimates systolic and diastolic pressure, when compared
      with the standard mercury sphygmomanometer. However, the degree of
      underestimation is small and appears consistent across a wide range of blood
      pressure levels.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7623371
TI  - Is blood pressure commonly raised by moderate consumption of liquorice?
AB  - It is well known that excessive liquorice intake can induce sodium and fluid
      retention, hypokalaemia, hypertension and inhibition of the renin-angiotensin
      system. We tested whether regular moderate liquorice consumption (50 g and 100 g
      daily) raises blood pressure (BP) in a normotensive population. Ingestion of 100
      g of liquorice daily (n = 30) caused a significant rise in systolic blood
      pressure (SBP) by a mean of 6.5 mm Hg (P < 0.001) and a fall in plasma potassium
      by 0.24 mmol/l (P < 0.001); the highest rise in SBP observed was 19 mm Hg. In a
      subgroup of 13 women the consumption of 50 g of liquorice daily also caused a
      significant rise in SBP of 5.6 mm Hg (P < 0.001) and DBP of 3.4 mm Hg (P =
      0.002). A significant change in the cortisol/cortisone ratio in urine was
      observed during 100 g liquorice consumption indicating inhibition of 11 beta
      hydroxysteroid dehydrogenase in kidneys. The results indicate that liquorice
      induced hypertension might be more common than has been appreciated and it
      important for medical doctors to be on the alert for this effect in both the
      prevention and treatment of hypertension.

PMID- 7623372
TI  - Altered circadian rhythm of blood pressure in shift workers.
AB  - The effect of shift work on the circadian rhythm of blood pressure (BP) was
      studied in male bakery workers. The study group consisted of 28 men, blue collar
      non-rotating shift workers, 20-60 years of age, and the control group comprised
      30 men, blue collar, day workers in the same age group. BP was evaluated in all
      subjects by 24h BP monitoring. Day workers showed typical circadian rhythm with a
      drop in both systolic and diastolic BP at night. This pattern was reversed in
      night workers. The peak SBP for night workers was at 11 pm and among day workers
      at 4 pm. Peak DBP was recorded among night workers at 10 pm and among day workers
      at 3 pm. All subjects showed a highly significant cyclic variation in BP. Whereas
      the range for SBP was similar in these two age groups (P > 0.05), the amplitude
      of DBP tended to be smaller in young workers. Therapeutic decisions for night
      shift workers with hypertension should take into account their altered BP cycle.

PMID- 7623373
TI  - Effect of low energy diet and weight loss on major risk factors, central obesity
      and associated disturbances in patients with essential hypertension.
AB  - Obesity, especially central, increases the risk of hypertension,
      hypertriglyceridaemia and diabetes to a significant extent. To determine whether
      dietary weight reduction can reduce blood pressure (BP) and other cardiovascular
      risk factors, 217 hypertensives were randomised to receive either 1600 Kcal/day
      diet (group A, n = 108) or the usual 2100 Kcal/day diet (group B, n = 109).
      Sodium intake and physical activity were kept similar in both groups. After 16
      weeks of follow-up, patients in group A received significantly less energy
      leading to a 2.8 kg net reduction in mean weight in association with a
      significant net decrease in mean SBP and DBP (7.5/6.5 mm Hg) compared with
      nonsignificant changes in group B. There was a significant net decrease in mean
      total cholesterol (7.0%), low-density lipoprotein (LDL)-cholesterol (7.9%) and
      triglycerides (8.0%), with a significant net increase in high-density lipoprotein
      (HDL)-cholesterol (4.0%) in group A compared with group B. New risk factors such
      as glucose intolerance (8.0%) and central obesity (waist-hip girth ratio, 0.021)
      showed a significant net reduction compared with group B. Patients with central
      obesity and other associated disturbances showed maximal reduction in BP and
      other cardiovascular risk factors with a significantly greater increase in HDL
      cholesterol. Mean doses of drugs were similar at entry to the study as well as
      after 16 weeks in both groups. It is possible that weight reduction due to a low
      caloric diet can moderate central obesity and associated disturbances in
      hypertensive subjects.

PMID- 7623374
TI  - Acute effects of flosequinan (BTS 49465) in untreated moderate to severe
      hypertension.
AB  - Flosequinan (BTS 49465, 7-fluoro-1-methyl-3-methyl-sulphinyl-4-quinolone), a
      recently direct-acting vasodilator that should cause relatively less reflex
      tachycardia, was given in a single oral dose of 200 mg to 10 untreated patients
      with moderate to severe hypertension. Flosequinan caused a fall in blood pressure
      (BP) from 181/116 +/- 7/4 to 161/102 +/- 5/4 mm Hg (P < 0.05). The proportional
      decrease of mean arterial pressure (MAP) was 14.6% (P < 0.01). Together with the
      decrease of BP an increase of heart rate from 79 +/- 5 to 96 +/- 5 beats/min
      occurred (31 +/- 4%, P < 0.01). Forearm blood flow increased insignificantly (NS)
      from 3.7 +/- 0.6 to 5.5 +/- 1.5 ml/100 ml/min together with a small decrease in
      forearm vascular resistance from 47 +/- 7 to 39 +/- 7 arbitrary units (NS).
      Forearm venous distensibility remained stable around 0.03% mm Hg (NS).
      Neurohormonal parameters showed the consequences of systemic vasodilation:
      noradrenaline rose from 1.25 +/- 0.10 to 2.88 +/- 0.34 nmol/l (P < 0.01),
      adrenaline from 0.16 +/- 0.03 to 0.35 +/- 0.10 nmol/l (NS), plasma renin activity
      from 2.33 +/- 0.46 to 3.27 +/- 0.73 ng/ml/h (P < 0.05) and aldosterone from 14.31
      +/- 2.47 to 26.3 +/- 8.02 ng/ml (P < 0.05). The serum concentrations of
      flosequinan and its major metabolite were within the therapeutic limits. Nine
      patients experienced minor side-effects such as headache, nausea and
      palpitations. We conclude that flosequinan has hypotensive efficacy with signs of
      systemic counter-regulatory mechanisms but without a clear forearm
      vasodilation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7623375
TI  - Rescue and replication signals of the adeno-associated virus 2 genome.
AB  - The adeno-associated virus 2 (AAV) genome is a single-stranded DNA which contains
      the inverted terminal repeats (ITRs) of 145 nucleotides. The terminal 125
      nucleotides of each ITR form palindromic hairpin structures that serve as primers
      for AAV DNA replication. These hairpin structures also play a crucial role in the
      integration, as well as the rescue, of the proviral genome from latently-infected
      cells, or from the recombinant AAV plasmids. However, the ITRs also contain an
      additional domain, designated the D-sequence, a 20-nucleotide stretch that is not
      involved in the formation of hairpins. In order to examine the role of the D
      sequence in viral DNA rescue and replication, a number of recombinant AAV
      plasmids were constructed which contained deletions/substitutions in different
      regions of the ITRs. The results presented here reveal the existence of
      additional sequences, other than the hairpin structures, which serve as primers
      for AAV DNA replication. The results also show that whereas the hairpin
      structures are sufficient for excision and replication of the viral DNA, the D
      sequence is crucial for the high efficiency of rescue and replication of the AAV
      genome.

PMID- 7623376
TI  - Chaperonins can catalyse the reversal of early aggregation steps when a protein
      misfolds.
AB  - Chaperonins use energy derived from ATP hydrolysis to enhance the efficiency of
      protein folding by a mechanism which remains a matter of debate. Here, we show
      that the kinetics of spontaneous and assisted folding of mitochondrial malate
      dehydrogenase are quantitatively described by a simple physical model. The
      protein folds from non-native chains by the slow formation of native-like
      monomers, which then dimerize to form the active enzyme. Misfolding proceeds by
      two phases of aggregation: the first is slowly reversible, the second is
      irreversible. Chaperonins accelerate the dissociation of the first-formed,
      unstable aggregates through a repeated binding-and-release cycle coupled to ATP
      hydrolysis. By this catalytic action, they supply the productive folding pathway
      with monomers, and block the irreversible phase of aggregation, thereby
      maintaining optimal folding yields even when present in sub-stoichiometric
      quantities. The hydrolytically active chaperonin is required until the substrate
      protein has completed the slow transition to its native-like, monomeric state.
      Both the observed rate of folding and the yield are increased by this mechanism
      without changing real rates in the productive pathway.

PMID- 7623377
TI  - Homology in structural organization between E. coli ClpAP protease and the
      eukaryotic 26 S proteasome.
AB  - Energy-dependent protein degradation is carried out by large multimeric protein
      complexes such as the proteasomes of eukaryotic and archaeal cells and the ATP
      dependent proteases of eubacterial cells. Clp protease, a major multicomponent
      protease of Escherichia coli, consists of a proteolytic component, ClpP, in
      association with an ATP-hydrolyzing, chaperonin-like component, ClpA. To provide
      a structural basis for understanding the regulation and mechanism of action of
      Clp protease, we have used negative staining electron microscopy and image
      analysis to examine ClpA and ClpP separately, as well as active ClpAP complexes.
      Digitized images of ClpP and ClpA were analyzed using a novel algorithm designed
      to detect rotational symmetries. ClpP is composed of two rings of seven subunits
      superimposed in bipolar fashion along the axis of rotational symmetry. This
      structure is similar to that formed by the beta subunits of the eukaryotic and
      archaeal proteasomes. In the presence of MgATP, ClpA forms an oligomer with 6
      fold symmetry when viewed en face. Side views of ClpA indicate that the subunits
      are bilobed with the respective domains forming two stacked rings. ClpAP
      complexes contain a tetradecamer of ClpP flanked at one or both ends with a
      hexamer of ClpA, resulting in a symmetry mismatch between the axially aligned
      molecules. Our findings demonstrate that, despite the lack of sequence similarity
      between ClpAP and proteasomes, these multimeric proteases nevertheless have a
      profound similarity in their underlying architecture that may reflect a common
      mechanism of action.

PMID- 7623378
TI  - Homeodomain proteins: what governs their ability to recognize specific DNA
      sequences?
AB  - Deformed (Dfd) and Ultrabithorax (Ubx) are homeodomain proteins from Drosophila
      melanogaster that exert regulatory effects on gene expression by binding to
      specific target sites in the fly genome using a helix-turn-helix (HTH) motif. The
      recognition helices of these two proteins are almost identical and the DNA
      sequences they recognize are similar, containing a conserved TAAT core sequence
      flanked by a somewhat variable sequence. Yet the in vivo functions of the two
      proteins are quite different. We have used the homeodomains of these two proteins
      and in vitro selected DNA binding sites to characterize the structural details of
      homeodomain binding to DNA and to understand the basis for the differences in
      sequence specificity between homeodomains with similar recognition helices. We
      have employed hydroxyl radical cleavage of DNA to study the positioning of the
      proteins on the binding sites and have analyzed the effects of missing
      nucleosides and purine methylation on homeodomain binding. Our results indicate
      that the positioning of the Ubx and Dfd homeodomains on their binding sites is
      consistent with reported structures of other homeodomain/DNA complexes. Dfd and
      Ubx bind to DNA with the recognition helix in the major groove 3' to the TAAT
      core sequence and the N-terminal arm in the adjacent minor groove. However, we
      observe striking differences between the two homeodomains in their specific
      interactions with DNA. Missing nucleosides within the selected binding sites have
      differential effects on protein binding, which are dependent on the identity of
      the homeodomain. Differences at the 3' end of the binding site on the top strand
      indicate that the N-terminal arm of a homeodomain is capable of distinguishing an
      A.T base-pair from T.A in the minor groove. Specific orientation of the N
      terminal arm within the binding site appears to vary between the homeodomains and
      influences the interaction of the recognition helix with the major groove.

PMID- 7623379
TI  - Mutation in Cys662 of Escherichia coli DNA topoisomerase I confers temperature
      sensitivity and change in DNA cleavage selectivity.
AB  - Cys662 is one of the 12 cysteine residues proposed to be co-ordination sites for
      binding of three Zn(II) in Escherichia coli DNA topoisomerase I. Oligonucleotide
      directed mutagenesis was used to convert Cys662 to either serine or histidine.
      The mutant enzymes were overexpressed and purified to homogeneity. Analysis of
      the purified enzymes demonstrated that the mutations resulted in loss of one
      tightly bound Zn(II). In vivo complementation tests and in vitro relaxation
      activity assays at different temperatures showed that the partial relaxation
      activities retained in the two mutant enzymes were temperature sensitive.
      Fluorescence measurements indicated that the wild-type and mutant enzymes have
      structural differences. When DNA cleavage specificity was examined, the mutant
      enzymes were found to have altered cleavage site preferences. The preferred
      cleavage sites of the wild-type enzyme all had a cytosine residue four
      nucleotides to the minus side of the break. The cleavage sites produced by the
      mutant enzymes did not show a preference for cytosine at that position.

PMID- 7623380
TI  - Membrane assembly of circularly permuted variants of the E. coli outer membrane
      protein OmpA.
AB  - The two-domain, 325 residue outer membrane protein OmpA is one of the most
      abundant proteins of Escherichia coli, playing a role in the maintenance of the
      integrity of the cell surface. The N-terminal domain, consisting of about 170
      amino acid residues, is embedded in the membrane, presumably in the form of a
      beta-barrel consisting of eight amphipathic transmembrane strands. Pairs of these
      proposed transmembrane strands were permuted at the DNA level, in order to
      dissect the process of membrane assembly. All three possible circular
      permutations led to variants, which were, in comparison with the wild-type
      protein, less efficiently assembled. In contrast, no membrane assembly could be
      detected in any of 18 non-circularly permuted variants. We take this as an
      indication that the "right" (wild-type) order of beta-strands is a necessary and
      sufficient prerequisite for at least partially successful membrane assembly. This
      may be the consequence of packing constraints and/or a failure to adopt the wild
      type arrangement of beta-strands, which require crossing of the periplasmic
      turns.

PMID- 7623381
TI  - The structure of chloroplast cytochrome c6 at 1.9 A resolution: evidence for
      functional oligomerization.
AB  - The molecular structure of cytochrome c6 from the green alga Chlamydomonas
      reinhardtii has been determined from two crystal forms and refined to 1.9 A
      resolution. The two crystal forms are likely the result of different levels of
      post-translational modification of the protein. This is the first report of a
      high-resolution structure of a chloroplast-derived class I c-type cytochrome. The
      overall fold is similar to that of other class I c-type cytochromes, consisting
      of a series of alpha-helices and turns that envelop the heme prosthetic group.
      There is also a short two-stranded anti-parallel beta-sheet in the vicinity of
      the methionine axial ligand to the heme; this region of the molecule is formed by
      the most highly conserved residues in c6-type cytochromes. Although class I c
      type cytochromes are assumed to function as monomers, both crystal forms of
      cytochrome c6 exhibit oligomerization about the heme crevice that is, in part,
      mediated by the short anti-parallel beta-sheet. The functional significance of
      this oligomerization is supported by the appearance of similar interfaces in
      other electron transfer couples, HPLC and light-scattering data, and is
      furthermore consistent with kinetic data on electron transfer reactions of c6
      type cytochromes.

PMID- 7623382
TI  - Structure of deoxyhaemoglobin of the antarctic fish Pagothenia bernacchii with an
      analysis of the structural basis of the root effect by comparison of the liganded
      and unliganded haemoglobin structures.
AB  - We have determined the structure of deoxyhaemoglobin from the antarctic fish
      Pagothenia bernacchii at pH 6.2 to a resolution of 2.2 A with X-ray data from a
      twinned crystal deconvoluted so as to approximate data from a single crystal. The
      R-factor between the (twinned) model and the observed data is 16% for reflections
      used in refinement and 22% for reflections not used in refinement. The T (deoxy)
      structure was compared with the R (liganded) structure at pH 8.0 in an attempt to
      understand the structural basis of the greater affinity for hydrogen ions of T,
      relative to R, that comprises the Root effect. Up to half of the effect can be
      attributed to interaction of the residues Asp95 (G1)alpha and Asp101 (G3)beta: in
      R the residues are far apart and their carboxyl groups are unprotonated, but the
      shift at the alpha 1 beta 2 interface that accompanies the R to T transition
      brings them so close that they appear to share a proton between them. The
      proximity of Asp99 (G1)beta may contribute to the required raising of the pKa
      values of the other two Asp residues. These and neighbouring residues are
      sufficiently conserved in the haemoglobins of trout (component IV), carp and
      bluefin tuna, all of which exhibit the Root effect, for the same mechanism to
      apply. However, the environment is equally conserved in haemoglobins of
      Trematomus newnesi (major component) and trout (component I), which do not
      exhibit the Root effect, so that the structural factors controlling the Asp-Asp
      interaction remain unclear. No other residue appears to undergo an R to T change
      in the immediate neighbourhoods that could account for any significant portion of
      the Root effect, so at least half of the effect must result either from long
      range electrostatic interactions or from a large number of local interactions.

PMID- 7623383
TI  - Three-dimensional solution structure of the calcium channel antagonist omega
      agatoxin IVA: consensus molecular folding of calcium channel blockers.
AB  - The three-dimensional solution structure of omega-agatoxin IVA, which is a
      specific blocker of the P-type calcium channel isolated from funnel web spider
      venom and has a molecular mass of 5.2 kDa, was determined by two dimensional 1H
      NMR spectroscopy, combined with simulated annealing calculations. On the basis of
      563 experimental constraints, including 516 distance constraints obtained from
      the nuclear Overhauser effect, 21 torsion angle (phi, chi 1) constraints, and 26
      constraints associated with hydrogen bonds and disulfide bonds, a total of 14
      converged structures were obtained. The atomic root mean square difference for
      the 14 converged structures with respect to the mean coordinates is 0.42 (+/-
      0.07) A for the backbone atoms (N, C alpha, C) and 0.95 (+/- 0.15) A for all
      heavy atoms of the central part (residues 4 to 38) constrained by four disulfide
      bonds. The N- and C-terminal segments (residues 1 to 3 and 39 to 48,
      respectively) have a disordered structure in aqueous solution. The molecular
      structure of omega-agatoxin IVA is composed of a short triple-stranded
      antiparallel beta-sheet, three loops, and the disordered N- and C-terminal
      segments. The overall beta-sheet topology is +2x, -1, which is the same as that
      reported for omega-conotoxin GVIA, an N-type calcium channel blocker.
      Irrespective of differences in the number of disulfide bonds and low primary
      sequence homology, these two peptide toxins show a significant structural
      similarity in three dimensions. The whole-cell voltage-clamp recording using rat
      cerebellar slices suggests that the hydrophobic C-terminal segment of omega
      agatoxin IVA, which does not exist in omega-conotoxin GVIA, plays a crucial role
      in the blocking action of omega-agatoxin IVA on the P-type calcium channel in rat
      cerebellar Purkinje cells. The present study provides a molecular basis for the
      toxin-channel interaction, and thereby provides insight into the discrimination
      of different subtypes of calcium channels.

PMID- 7623384
TI  - Complete 1H nuclear magnetic resonance assignments and structural
      characterization of a fusion protein of the alpha-amylase inhibitor tendamistat
      with the activation domain of the human immunodeficiency virus type 1 Tat
      protein.
AB  - Complete sequence-specific assignments of the 1H-NMR spectrum of a fusion protein
      of the alpha-amylase inhibitor tendamistat from Streptomyces tendae and the
      activation domain of Tat from human immunodeficiency virus type 1 (HIV-1) was
      obtained by homonuclear two-dimensional NMR methods. The protein behaves as
      expected for an ideal fusion protein: the flexible linker allows an almost
      completely decoupled motion of the subunits of the protein and the two subunits
      show almost no mutual interaction. In the tendamistat part, small structural
      distortions due to exchange of the carboxy-terminal leucine propagate mainly via
      the hydrogen bonds of the beta-sheet and the disulfide bond. The Tat part of the
      protein contains the seven cysteine residues of full-length Tat. The fusion
      protein was expressed in Streptomyces lividans and exported. During the export to
      the extracellular space disulfide bonds are created by the expressing cells, only
      one sulfhydryl group remains accessible for sulfhydryl reagents. Although a
      unique, dominant conformation with a specific disulfide bonding pattern exists, a
      significant conformational variation can be observed including cis-proline
      peptide bonds, which may indicate smaller populations with alternative disulfide
      bonding patterns.

PMID- 7623385
TI  - Thermodynamics of unfolding of ribonuclease A under high pressure. A study by
      proton NMR.
AB  - Thermodynamic stability of ribonuclease A (6.2 mM pH 1.0, 0.15 M KCl, in 2H2O)
      has been studied in the pressure range of 1 to 2000 atm and in the temperature
      range of 7.5 to 40 degrees C with a high pressure 1H NMR technique at 400 MHz.
      His epsilon proton resonances were used as reporter groups to measure fractions
      of folded and unfolded species. Gibbs energy differences between folded and
      unfolded species were obtained as functions of pressure for different
      temperatures and as functions of temperature for different pressures. The volume
      increase upon unfolding, delta V, was negative and temperature-dependent,
      decreasing from -10 ml/mol at 7.5 degrees C to -30 ml/mol at 37 degrees C. From
      the least squares-fitting of experimental Gibbs energy differences to a
      theoretical expression holding pressure and delta Cp constant, we determined best
      fit values of delta G, delta H, delta S and delta Cp for different values of
      pressure in the temperature range 7.5 to 40 degrees C. We found that delta Cp is
      dependent on pressure, decreasing from 1.79 kcal/mol K at 1 atm to 1.08 kcal/mol
      K at 2000 atm. These findings appear to be consistent with a notion that the
      state of hydration of non-polar side-chains upon unfolding of the protein is a
      major factor that determines the pressure dependence of the conformational
      stability of ribonuclease A under the chosen experimental condition.

PMID- 7623386
TI  - Local perturbations by ligand binding of hydrogen deuterium exchange kinetics in
      a four-helix bundle protein, acyl coenzyme A binding protein (ACBP).
AB  - Amide hydrogen exchange kinetics of the individual amides in a four-helix bundle
      protein, acyl-coenzyme A binding protein, have been studied by nuclear magnetic
      resonance spectroscopy. The kinetics of amides with exchange rate constants in
      the range of 10(-25) to 10(-6.5) S-1 at pH 6.65 in free protein and the ligand
      protein complex have been measured, and the effect of binding the ligand,
      palmitoyl-coenzyme A, on individual exchange rates has been analysed. Specific
      correlations between exchange kinetics and the structural properties of the
      individual amides known from the three-dimensional structure of acyl-coenzyme A
      binding protein have been examined. Furthermore, an analysis has been performed
      comparing the structural perturbations of the protein-ligand interactions known
      from the three dimensional structure of the complex of palmitoyl-coenzyme A and
      acyl-coenzyme A binding protein with the ligand-induced perturbations on the
      amides exchange kinetics. Finally, the ligand-induced perturbations on hydrogen
      exchange have been compared with those on 15N relaxation. The results suggest
      that hydrogen exchange kinetics in the individual sites of acyl-coenzyme A
      binding protein are primarily determined by local structural features; they show
      that ligand binding gives rise mainly to changes localized at the sites of
      interaction between protein and ligand; they imply that the perturbation of
      exchange kinetics caused by ligation can be either, as in one example a local
      stabilisation of the pre-exchange equilibrium induced by formation of a hydrogen
      bond, or as seen here in several examples a reduction of the dynamic processes
      that lead to the opening and closing processes of the pre-exchange equilibrium.
      The results seem not to indicate changes in the rate of the final chemical
      exchange step.

PMID- 7623387
TI  - Problem-solving types among high-risk IDUs. Potential treatment implications.
AB  - This research investigated whether high-risk injection drug users (IDUs) manifest
      distinct types, or profiles, of interpersonal cognitive problem-solving (ICPS)
      abilities. Four measures of ICPS, the Means-Ends Problem-Solving procedure
      (MEPS), Optional Thinking Test (OTT), Awareness of Consequences Test (ACT), and
      Causal Thinking Test (CTT), were administered to 140 IDUs who volunteered for
      NIDA Demonstration Projects in Newark and Jersey City, NJ, to study high-risk
      behaviors in drug users and their sexual partners. At time of initial contact,
      none of the subjects was currently enrolled in a treatment program. Hierarchical
      and nonhierachical cluster analyses were used with the MEPS, OTT, ACT, and CTT
      scores, and five IDU problem-solving types were identified. These types
      represented below-average, causal, generational, consequential, and above-average
      problem-solving skills. A rational conceptualization of potential treatment
      implications for each of these types of IDU problem solvers is discussed.

PMID- 7623388
TI  - Effects of ethnicity on low-dose opiate stabilization.
AB  - In a recent randomized clinical trial using buprenorphine (2 and 6 mg) and
      methadone (35 and 65 mg), we compared low-level opiate withdrawal symptoms among
      Whites (n = 84), Hispanics (n = 20), and African Americans (n = 21). During the
      first 2 months of opiate stabilization, persistent low-level opiate withdrawal
      symptoms were significantly lower in African-Americans and Hispanics than in the
      white patients. As expected pharmacologically, this relative underreporting of
      low-level withdrawal by minority patients was greater for the low opiate doses
      (buprenorphine 2 mg and methadone 35 mg). This underreporting may reflect
      sociocultural as well as biological differences, because subjective, but not
      objective, withdrawal symptoms showed this ethnic difference.

PMID- 7623389
TI  - An intensive outpatient approach for cocaine abuse treatment. The Matrix model.
AB  - The Matrix model of outpatient treatment was developed during the 1980s in
      response to an overwhelming demand for cocaine abuse treatment services. The
      model was constructed using components based upon empirically supported findings
      from the substance abuse research field. Over the course of development, data
      were collected on the treatment model and the model was modified based upon
      empirical evaluation. A pilot study comparing the Matrix outpatient model with an
      inpatient hospital treatment program produced preliminary support for the
      clinical utility of the model. An open trial comparing publicly and privately
      funded patients demonstrated that patients with fewer resources were more
      difficult to engage and retain in this model of outpatient treatment. In a
      controlled trial, a clear positive relationship was documented between duration
      and amount of treatment involvement in the Matrix model and positive outcome at 1
      year. Due to a variety of methodological issues, the study was not able to answer
      definitively the question of clinical efficacy. In all of these studies, patients
      treated with the Matrix model demonstrated statistically significant reductions
      in drug and alcohol use and improvements in psychological indicators. This body
      of work, along with the public acceptance the model has received in the treatment
      community, support the usefulness of this intensive outpatient approach for
      cocaine abuse. Further research is underway to provide additional controlled
      information on the value of this treatment approach.

PMID- 7623391
TI  - Dr. A. Thomas McLellan and colleagues' response regarding evidence for
      effectiveness of acupuncture:.

PMID- 7623390
TI  - Treatment for mental illness and substance abuse in a public psychiatric
      hospital. Successful strategies and challenging problems.
AB  - Although the literature on dual diagnosis has grown considerably over the last
      several years, report describing inpatient treatment models are less common. We
      describe some of the major treatment concerns in the dural diagnosis literature,
      such as using 12-step self-help programs like Alcoholics Anonymous (AA) or
      Narcotics Anonymous (NA), dealing with different stages of treatment, and
      developing a program with integrated substance abuse and psychiatric treatment.
      The practical application of these treatment issues is featured by showing how
      they are incorporated into an innovative inpatient dual diagnosis treatment
      program at a public psychiatric hospital. Finally, the treatment program is
      described in detail regarding administrative issues, staff training, daily
      treatment schedules, and patient demographics.

PMID- 7623392
TI  - Practice guidelines in the addictions. Recent developments.
AB  - Consensually established principles of clinical conduct, known variously as
      practice guidelines, standards, protocols, or algorithms, have proliferated
      throughout medicine over the past decade. Institutional and disciplinary efforts
      to develop and promulgate guidelines for the treatment of additive disorders have
      recently been initiated. We review guideline development activities of the
      American Psychiatric Association, American Psychological Association, American
      Society of Addiction Medicine, American Nurses Association, National Association
      of Social Workers, and Center for Substance Abuse Treatment of the Substance
      Abuse and Mental Health Services Administration. Medical care performance and
      outcome assessments are discussed with attention to the role they can play in
      evaluating and refining guidelines. Potential effects of guidelines, salutary and
      deleterious, on clinical practice in the addictions are delineated.

PMID- 7623393
TI  - Alcohol, drugs, and urban violence in a small city trauma center.
AB  - Substance abuse and urban trauma go hand in hand. But research focuses on large
      cities served by major academic medical centers. Do small cities face the same
      problems? Two hundred thirty-three urban trauma inpatients from a metro area of
      250,000 were studied using patient interviews and medical records. As in large
      cities, one half used alcohol or drugs when attacked. Seventy percent were likely
      to be young, male, poor African-Americans. Only 3% were gang members, but
      demographic characteristics failed to explain substance abuse as they have for
      larger cities. A culture of violence pervades the small city, as it does in large
      urban ghettos. Two fifths were repeat urban trauma victims. Two fifths witnessed
      assaults in the past year. One third carried a knife or gun. Fifteen percent used
      a weapon on another person in the last year. Contextual variables, like being
      hurt in a bar, were related to drinking and drugs. The best predictor of present
      substance abuse and urban trauma was medical history of substance abuse. The need
      for (a) toxicology screens for all trauma victims, (b) referrals to substance
      abuse programs, (c) targeting at-risk populations for prevention, and (d)
      eliminating environments fostering violence and substance abuse is supported.

PMID- 7623394
TI  - Treatment of crack-cocaine-induced compulsive behavior with trazodone.
AB  - Foraging is a compulsive behavior of searching for pieces of crack cocaine that
      the individual believes might have been accidentally misplaced. Three clinical
      cases of compulsive foraging behavior associated with crack cocaine are
      described. Due to the development of side effects secondary to the antidepressant
      desipramine, the patients were switched to the antidepressant trazodone. The use
      of trazodone led to remission of the foraging behavior. The authors hypothesize
      this remission was due to trazodone serotonin reuptake inhibitory action. In all
      three cases, the patients did not relapse into abusing crack cocaine.

PMID- 7623395
TI  - Treating cigarette smoking in drug-abusing clients.
AB  - Clients in substance abuse treatment are at high risk for smoking-related illness
      due to higher rates and heavier smoking than the general population. Three myths
      widely held by both treatment staff and substance abusers in treatment-people in
      treatment do not want to quit smoking, people in treatment will relapse to other
      drug use if they attempt to quit smoking, and people in treatment are unable to
      quit smoking-make it difficult to broach the matter of smoking cessation. A 16
      week, cognitive-behavioral group program with nicotine patches was conducted at
      Oregon's largest, private, nonprofit substance abuse treatment agency. Of 490
      clients, approximately 85% of whom smoke, 106 (25% of the smokers) were
      interested enough in quitting to attend an orientation. Approximately 40% of
      these were methadone maintenance clients. The others were distributed among two
      residential and two outpatient drug-free treatment services. Of 90 assigned, 68
      began voluntary treatment, and 21 were assigned to delayed treatment. Of the 66
      smokers who began, 74% succeeded in quitting smoking for at least 1 day, and 23%
      were abstinent for at least 4 continuous weeks. At the end of the 16-week
      treatment, 7 subjects (11%) were abstinent. No control subjects quit smoking on
      their own. The article discusses issues of institutionalizing smoking cessation
      services in drug treatment agencies.

PMID- 7623396
TI  - Obtaining follow-up interviews for treatment evaluation.
AB  - Studies of the outcomes of substance abuse treatment are often handicapped
      because of subjects lost to follow-up. While follow-up data may be obtained from
      several sources, the follow-up interview often serves as the principal source of
      data. Difficulties are regularly encountered in locating and interviewing
      subjects not in treatment. From review of the literature on follow-up methodology
      and our own experience, we identified 10 procedures for effective follow-up.
      Application of these procedures is illustrated in a follow-up study of illicit
      opioid users treated in a methadone maintenance program. Follow-up interviews
      were obtained with 98% of the subjects. We recommend use of the 10 procedures by
      follow-up researchers, and we also recommend review of several previous
      publications on follow-up methodology.

PMID- 7623397
TI  - Reactive arthritis associated with an amebic liver abscess.

PMID- 7623398
TI  - Typhoid orchitis.

PMID- 7623399
TI  - Practical epidemiology and biostatistics in research. Study design and
      statistics.
AB  - Soundly planned study may well lead to the findings that are of wide scientific
      application and interest. This paper is intended to provide a simple and
      systematic guideline pertinent to the design, analysis and interpretation of
      studies, especially in the health care. It emphases on the importance of
      'Statistics' in the design, conduct, analysis and interpretation of the studies.
      It is pointed out that all the stages of research studies are vulnerable to
      statistical mismanagement. The most important thing is to balance the interests
      of the individuals in the study with those of the much larger number who may
      benefit in the long run. Concerning the proper use of statistics, the following
      things are recommended. (a) Statistical advice is needed at the planning stage of
      a project and not at its end; (b) statistical advice may be saught at almost
      every stage of a project; (c) the important aspects of logic and correctness of
      argument may be carefully looked before interpreting the results and (d) finally,
      before getting any work published, opinion of an expert statistician must be
      saught, so that erroneous conclusions may not become enshrined as the truth.

PMID- 7623400
TI  - Investigating the thyroid gland.

PMID- 7623401
TI  - Time to revise the MBBS curriculum.

PMID- 7623402
TI  - Evaluation of M/H ratio for screening of beta thalassaemia trait.
AB  - This study was done to evaluate the efficiency of M/H ratio between the
      percentages of microcytic and hypochromic cells as a screening procedure for
      thalassaemia trait in Pakistani population. A total of 150 subjects, were
      included in this study. The analysis of results revealed that M/H ratio is a very
      sensitive index for beta thalassaemia trait. The sensitivity, predictive value
      and diagnostic accuracy of the M/H ratio for beta thalassaemia trait was 100%,
      90.4% and 90.4% respectively. It also picked up all cases of beta thalassaemia
      trait with co-existent iron deficiency. It is therefore concluded that M/H ratio
      is an easy, reliable and sensitive index which can be used for mass screening of
      beta thalassaemia trait, particularly in a population where iron deficiency is
      also prevalent.

PMID- 7623403
TI  - Obstetrics hysterectomy--five years experience at Jinnah Postgraduate Medical
      Centre, Karachi.
AB  - During the five years period (1st January 1988 to 31st December 1992), 106
      hysterectomies were performed for obstetric indications in the Department of
      Obstetrics and Gynaecology, Jinnah Postgraduate Medical Centre (JPMC), Karachi.
      The frequency was 1 in 331 deliveries (total 35,172 deliveries). In all except
      one hysterectomy was performed as a life saving measure. The major indications
      were ruptured uterus in 61 (58%) cases and severe postpartum haemorrhage due to
      uterine atony in 18 (17%). Other indications included haemorrhage due to placenta
      praevia in 11 (10%), placenta accreta 7 (7%) and abruptio placentae 5 (5%),
      severe infection 2 (2%) and broad ligament haematoma following caesarean section
      1 (1%). There were 10 (9%) maternal deaths all due to severity of the conditions
      necessitating hysterectomy. Obstetric hysterectomy can save many lives but
      requires proper judgement and skill. Senior resident staff in obstetric units in
      the developing countries should be trained for it.

PMID- 7623404
TI  - Healing and relapse rates of duodenal ulcer with omeprazole vs ranitidine.
AB  - The efficacy of omeprazole 20 mg a day was assessed against ranitidine 150 mg
      twice a day in the healing and relapse of duodenal ulcer. Forty three
      endoscopically verified cases were allocated to 2 weeks of treatment, which was
      extended to 4 weeks, if the ulcer persisted on day 15. Two cases were excluded
      due to deviation from the protocol. Of 41 evaluable cases, 21 received omeprazole
      and 20 ranitidine. Healing rates with omeprazole and ranitidine at 2 weeks were
      71% and 70% respectively which rose to 100% and 90% at 4 weeks (N.S). There was
      no significant difference in pain relief in two groups. Follow-up endoscopies, in
      33 healed cases revealed 100% relapse at 3 months in omeprazole and 79% in
      ranitidine treated cases (P < 0.05).

PMID- 7623405
TI  - Cholera admissions in adults 1989-1994: a hospital based study.
AB  - In order to gain insight into the distribution of cholera over the years and
      proportion of monthly admissions under our adult medical services, we scrutinized
      our records of hospital discharges between 1989 and 1994. Only culture positive
      cases were included. Each year most of the cases of cholera are admitted between
      May and November with almost disease free interval from December to April. In
      1992 admission rate was 4.24/1000 medical admissions which increased to 12.65 in
      1993 and 13.73 in 1994. Though the Vibrio cholerae 01 Ogawa was the major isolate
      upto May, 1993, Vibrio cholerae non-01 serogroup 0139 dominated between June and
      August, 1993. Ogawa strain re-established itself in October, 1993. In August,
      1994, non-01 strain reappeared and became the major isolate in September. Cholera
      has caused multiple epidemics throughout the Indian subcontinent. Since 1800,
      there have been seven pandemics of cholera. The seventh pandemic originated in
      Indonesia and continues today.

PMID- 7623406
TI  - Piezogenic papules--a study of 100 cases.
AB  - Hundred people were examined for piezogenic papules (cutaneous hernia). Of these
      80 had pedal papules, 86 wrist papules and 74 both pedal and wrist papules. Most
      of these papules were bilateral and multiple. All cases examined were painless.
      Biopsy showed fragmentation of dermal elastic tissue and herniation of
      subcutaneous fat into the dermis. Histology was similar for both pedal and wrist
      papules.

PMID- 7623407
TI  - Deletions and duplication in internal inverted repeat sequence of long
      region/unique sequence of long region (IRL/UL) of herpes simplex virus type-1
      (HSV-1) genome are not evidently associated with intracranial and foot-pad
      pathogenicity in mouse model.
AB  - The biological properties of three deletion variants (1704, 1705 and 1706) of
      herpes simplex virus type-1 (HSV-1) strain 17 syn+, were studied by establishing
      a base line pathogenicity of nine individual plaques from the parental 17 syn+
      elite stock. Restriction enzyme analysis of deoxyribonucleic acid (DNA) from each
      of the nine plaque stocks and intracranial inoculation into three weeks old
      BALB/c mice showed no difference in the size of fragments and distribution of the
      sites or their 50% lethal dose (LD50) values [plaque forming units (pfu)/mouse]
      as compared to the parental 17 syn+ stock. Inoculation of the variants into three
      weeks old BALB/c mice showed that 1705 was not different in pathogenicity from
      the wild type following intracranial and footpad inoculations. On the other hand
      variants 1704 and 1706, when compared to the wild type virus were less virulent
      on intracranial inoculation i.e. the difference in LD50 values was approximately
      one log and two logs respectively and both the variants failed to kill any of the
      animals following footpad inoculation even at the dose of 1 x 10(7) pfu/mouse.
      During in vivo replication experiment in the peripheral nervous system of mice,
      1704 and 1706 grew very poorly.

PMID- 7623408
TI  - Latent phenotype analysis of three deletion variants of herpes simplex virus type
      1 (HSV-1) in mouse model.
AB  - Latency analysis of three herpes simplex virus type 1 (HSV-I) strain 17 syn+
      deletion variants (1704, 1705 and 1706) showed that they established, maintained
      and reactivated from latency. The kinetics of reactivation of 1705 and 1706 were
      similar to the parent HSV-1, 17 syn+, in which reactivation occurred 5-6 days
      post-explanation, but 1704 reactivated with delayed kinetics i.e. on the 12th day
      post-explantation. Since 1704 has deleted both copies of the latency associated
      transcripts (LATs) promoter region and one copy of the LAT coding region in
      internal inverted repeat sequence of long region (IRL), it was concluded that the
      LATs play a part in latency reactivation of 1704 from dorsal root ganglia (DRG)
      of spinal cord in mouse model. Restoration of the deleted sequences in the
      variant 1704 by marker rescue with the wild type BamHI b fragment resulted in a
      wild type genotype. This virus was designated as 1704R. Latency studies of 1704R
      revealed that the rate and frequency of reactivation was intermediate between 17
      syn+ and 1704, suggesting a secondary undetected mutation affecting latency
      phenotype. Isolation of 1704LP-, during the same marker rescue experiment in
      which both copies of promoter region of the LAT are deleted and reactivation of
      this virus from latency with delayed kinetics confirms that the LATs play a role
      in reactivation from latency.

PMID- 7623409
TI  - [Study on Pseudomonas aeruginosa cytotoxin and cytotoxin-converting phages].

PMID- 7623410
TI  - [Bacterial drug efflux proteins].

PMID- 7623411
TI  - [Current topics of receptor proteins for heat-stable enterotoxin produced by
      enterotoxigenic Escherichia coli].

PMID- 7623412
TI  - [The role of cytokines in endotoxin activities].

PMID- 7623413
TI  - [New structures recently found in and around the center of biological activities
      of LPS (endotoxin)].

PMID- 7623414
TI  - [Escape mechanism of Neisseria gonorrhoeae and disseminated gonococcal
      infection].

PMID- 7623415
TI  - [Colony morphology and multicellular behavior of bacteria].

PMID- 7623416
TI  - [Bacterial enterotoxins bearing superantigenic properties].

PMID- 7623417
TI  - [Electron-microscopic observation of pore formation in the erythrocyte membrane
      by streptolysin O].

PMID- 7623418
TI  - [Lyme disease and Borrelia].

PMID- 7623419
TI  - [International cooperation (ODA) in the field of microbiology].

PMID- 7623420
TI  - [Incidence and serotypes of Salmonella in apparently healthy swine at
      slaughterhouses in Japan: 1975-1989].
AB  - To find healthy Salmonella carriers among swine, isolation of Salmonella from
      fresh cecum samples was attempted at slaughterhouses in Tokyo, Saitama, and
      Tochigi during a period of 11 years. Of a total 3,058 samples, 1,341 were
      collected between 1975 and 1979, and the other 1,717 between 1984 and 1989. The
      overall isolation rate of Salmonella was 13.3% (408 pigs). The rate was 23.1%
      between 1975 and 1979 and 5.7% between 1984 and 1989. A total of 1,037 isolates
      were identified as Salmonella and classified into 28 serotypes. These serotypes
      involved Salmonella typhimurium (26.1%), S. derby (25.4%), and S. london (9.5%).
      However, the detection rate of these serotypes varied from year to year. Two
      serotypes were detected from each of 37 pigs and three from a pig. Of these 38
      pigs, 27 carried the serotypes of S. typhimurium or S. derby or both. The present
      study revealed that Salmonella carriers were highly frequent among healthy swine
      in Japan in 1970s, but decreased in 1980s.

PMID- 7623421
TI  - [Comparison by SES-PAGE of molecular weights of lipopolysaccharides from
      Campylobacter jejuni Lior serotype reference strains and clinical isolates].
AB  - To compare the molecular weights (MWs) of lipopolysaccharides (LPSs) from 30 Lior
      serotype reference strains and 17 clinical isolates of Campylobacter jejuni, we
      analyzed their migration rates by SDS-PAGE and the silver staining of the gel.
      LPSs from the serotype strains showed one band in the low-molecular-weight region
      of the gel as did those from R mutants of enterobacteria. Based on those from
      Salmonella minnesota R mutants, MWs of LPSs from C. jejuni strains were
      calculated to fall within a range of 3900 to 5300. Furthermore, in comparison of
      MWs of LPSs from the clinical isolates with those from the same serotype
      reference strains, six out of eight serotypes did not coincide each other. These
      results indicate that the Lior method is unrelated with the Penner method in the
      serotyping of C. jejuni.

PMID- 7623423
TI  - [The 79th Congress of the Medico-Legal Society of Japan. Yamagata, May 24-26,
      1995. Abstracts].

PMID- 7623422
TI  - [Adherence to HEp-2 cells of enterotoxemic Escherichia coli O-group 139 from pigs
      with edema disease].
AB  - One hundred and one strains of enterotoxemic Escherichia coli (ETEEC) O-group 139
      isolated from swine with edema disease were investigated for their adherence to
      HEp-2 cells in the presence of D-mannose. All strains adhered in large numbers to
      the cells (21 to 60 bacteria/cell). No correlation was found between the presence
      of F107 fimbria on the organisms and the adherence to the cells. Adhesion
      inhibition tests showed that anti-K12 serum inhibited the adhesion ETEEC O-group
      139 (an inhibition rate of 63 to 65%), but anti-F107 or anti-O139 sera did not.
      These results indicate that the capsular K12 antigen may be one of the pathogenic
      factors of ETEEC O-group 139.

PMID- 7623425
TI  - Effect of growth hormone treatment on glucose tolerance in a patient with
      cystinosis after kidney transplantation.
AB  - A 16 year-old boy with nephropathic cystinosis and kidney transplantation was
      successfully treated with rhGH because of growth retardation. After 15 months of
      rhGH therapy he developed impaired glucose tolerance. Various causes like
      cystinosis itself, the immunosuppressive therapy with cyclosporine A and
      cortisone, but rhGH too might have been the responsible factors for that.
      Treatment with rhGH was initiated again after 4 months of interruption of therapy
      because no relation between impaired glucose tolerance and GH could be
      established.

PMID- 7623424
TI  - [High dosage immunoglobulin therapy in Rhesus incompatibility].
AB  - From September 1992 to the end of August 1993 we treated fourteen children who
      suffered from rhesus hemolytic disease with high-dose intravenous immune globulin
      G. Eleven patients did not require an exchange transfusion, three needed an
      exchange transfusion despite immune globulin therapy. Although an exchange
      transfusion cannot be avoided in all patients, this new method is an important
      addition to the currently available possibilities of treatment. It is without
      adverse side effects and helps to lower the number of exchange transfusions.

PMID- 7623426
TI  - [Long-term follow-up of a boy with recurrent hypoglycemia and cholestasis in
      congenital growth hormone deficiency].
AB  - We report on a four-year-old boy with congenital growth hormone deficiency who
      first presented at age 13 weeks with jaundice and recurrent hypoglycemia. Growth
      hormone deficiency was diagnosed two years later, after cholestasis and
      hypoglycemia had almost completely disappeared, but length deficiency became
      apparent. The reason for the association of cholestasis with growth hormone
      deficiency remains unexplained. Cholestasis can, especially in combination with
      hypoglycemia, be a first sign of congenital growth hormone deficiency.

PMID- 7623427
TI  - [Severe acquired protein S deficiency with thrombophlebitis after febrile
      infection in a 7-year-old girl].
AB  - The importance of the anticoagulant properties of protein S is illustrated by the
      high incidence of thromboembolic events in individuals with protein S-deficiency.
      A 7 year old girl was hospitalized with purpura-like bruises and lesions on both
      thighs after she had suffered from febrile infection. A subsequently developing
      thrombosis of the left V. femoralis was treated successfully with urokinase.
      Haemostaseological investigations showed no signs of disseminated intravascular
      coagulation. However, isolated severe degradation or all protein S-components due
      to the presence of a circulating autoantibody to protein S was found. After
      several months the antibody was detectable not any more, activity and antigens of
      protein S were normal.

PMID- 7623428
TI  - [Heterotopic gray matter: MR findings and clinical aspects].
AB  - Heterotopias are conglomerates of neurons and glial cells in an abnormal location
      and belong to a group of malformations, which are the result of a disturbed
      migration of neurons during the embryonic development of the brain. The MRI
      appearance and clinical symptoms of 14 patients with nodular or lamellar
      heterotopias are presented. Seizures were the leading symptom (12 of 14
      patients), in children also a developmental deficit (4/10) with or without
      seizures. Most of the children (9/10) had further brain malformations especially
      of the corpus callosum or the cerebellar vermis. Nodular heterotopias without
      further malformations were found in 4 patients, two of them developing grand-mal
      seizures after childhood. On MRI heterotopias are characterized by a signal
      isointense to gray matter in all sequences. MRI-scans in at least 2 orientations
      are necessary to detect these anomalies reliably. MRI is the optimum method for
      the demonstration of these anomalies and should always be performed if seizures
      develop during childhood. At least in nodular heterotopias there is no definite
      correlation between the extent of the anomalies, the EEG-findings and the
      clinical symptoms. However there is a frequent combination of heterotopias with
      further cerebral malformations.

PMID- 7623429
TI  - [Growing septum pellucidum cyst in infancy].
AB  - We report a baby's development with expanding cyst of the septum pellucidum. It
      was detected accidentally during diagnostic evaluation of epileptic convulsions
      and psychomotoric retardation. The dramatic increasing of the cyst was followed
      by cranial ultrasonography for ten months. The progression of clinical symptoms
      couldn't be explained because after drainage of the cyst, no improvement took
      place. MRT with Spectroscopy lead to the tentative diagnosis, Morbus Alexander.
      This couldn't be proved because no biopsy of the brain was performed against the
      decision of the child's mother, nor postmortal (the child died at 20 months).

PMID- 7623430
TI  - [Achalasia, alacrimia and cortisol deficiency--Allgrove syndrome].
AB  - Review of a rare multisystem disorder with the main symptoms achalasia of the
      esophagus, alacrimia and glucocorticoid deficiency as well as multiple other
      symptoms especially of the nervous system. Report of one case diagnosed in the
      age of 11.5 years with a case history of about 7 years. Description of the danger
      to live of the affected patients primarily by the underlying glucocorticoid
      deficiency in various stages with bearing the peril of hypoglycemic shock and
      even death after heavy stress conditions.

PMID- 7623431
TI  - [Comment on F. Kullmann, R. Koch, W. Feichtinger, H. Giesen, M. Schmid, T. Grimm,
      Holt-Oram syndrome with reciprocal translocation, pulmonary hypoplasia and
      cardiomyopathy].

PMID- 7623432
TI  - [The neurotic conversion disorder spectrum in neuropediatrics].
AB  - The incidence and symptomatology of conversion disorders in a neuropaediatric
      department was described. One year was retrospectively evaluated. From totally 12
      patients with conversion disorders 7 were suffering for an impaired walk and each
      1 patient for visual defect, choreoathetosis and confusion, convulsive seizures,
      tic, paralysis. "Conversion disorder" is an important and often ignored diagnosis
      in neuropaediatrician.

PMID- 7623433
TI  - Late form of vitamin K deficiency bleeding in Germany.
AB  - BACKGROUND: The evaluation of the disease of vitamin K deficiency bleeding
      (VKDB). METHOD: 108 reported cases between 1980 and 1990 from Germany. RESULTS:
      VKDB occurs preferentially (90%) in fully breastfed infants, males are affected
      nearly twice as often as females. The peak age is four weeks; the majority (79%)
      of the infants are between three and seven weeks old. 58% of the patients suffer
      from intracranial bleeding, which results in a total mortality rate of 19% and in
      neurological damage in 21%. Generally the VKDB occurred suddenly as no warning
      signs were noticed or they were so insignificant as not to be heeded. In at least
      37% of the patients cholestasis was detected. The Quick value was pathologically
      low in every case. Vitamin K dependent factors were low and PIVKA was detectable,
      whereas vitamin K independent hemostatic parameters were normal or even elevated.
      The combination of low Quick value and normal fibrinogen as well as platelet
      level is a good diagnostic indicator which can be confirmed by administration of
      vitamin K, after which the Quick value will rise within 30 minutes. Vitamin K
      prophylaxis reduces the incidence of VKDB from 5.13 per 100,000 births to a tenth
      of that; single dose oral prophylaxis reduces the risk by a factor of 3.3 and a
      single parenteral dose by 14.3. Parenteral prophylaxis is more effective in
      patients with hepatobiliary disorders. Patients who suffered VKDB despite having
      received vitamin K prophylaxis are older at onset (without prophylaxis 32 days,
      with oral prophylaxis 37 days, and with parenteral prophylaxis 63 days) and have
      less intracranial bleeding (35%) than patients who received none (62%).
      CONCLUSION: Late form of VKDB is a rare but serious disease which can be
      prevented by VK-prophylaxis.

PMID- 7623434
TI  - [Immune thrombocytopenia in childhood--how much diagnosis and therapy is
      reasonable?].
AB  - Acute and chronic ITP in childhood are both relatively mild diseases that only
      rarely result in live threatening complications. In most cases diagnostic
      measures can be limited to a detailed history, thorough physical examination, a
      complete blood count and evaluation of platelet size on smear. A bone marrow
      aspirate is only necessary if the diagnosis of ITP is not straightforward.
      Because of large platelet size and vascular stability bleeding tendency in
      childhood ITP is mild even with very low platelet counts. 90% of children with
      acute IPT recover spontaneously within 12 months. Therefore therapy can safely be
      limited to a few situations: necessary surgical intervention during
      thrombocytopenia, live threatening bleeding, major trauma. In most instances
      optimal management of ITP consists in a "wait and see" approach in addition to
      giving detailed and thorough information to patients or parents about the benign
      nature of the disease, the likelihood of spontaneous recovery and the importance
      of avoiding aspirin and contact sports. Controversies in regards to diagnosis and
      therapy of ITP in childhood are discussed and the various therapeutic
      possibilities are presented.

PMID- 7623435
TI  - Evaluation of prenatal treatment in newborns with cobalamin-responsive
      methylmalonic acidaemia.

PMID- 7623436
TI  - Severely depressed natural killer cell activity of patients with
      adrenoleukodystrophy under treatment with Lorenzo's oil.

PMID- 7623437
TI  - Linkage and association.

PMID- 7623438
TI  - Characterization of the mutations in the glucose-6-phosphatase gene in Israeli
      patients with glycogen storage disease type 1a: R83C in six Jews and a novel
      V166G mutation in a Muslim Arab.
AB  - Glycogen storage disease type 1a (GSD 1a), an autosomal recessive disease, is
      caused by the inactivity of glucose-6-phosphatase, the gene of which has been
      recently cloned. We report on the missense mutation C-->T at nucleotide 326 of
      the G6Pase gene, causing the change of the Arg codon at position 83 into a Cys
      codon, as the single mutation detected in six Jewish patients. This finding
      suggests that this mutation might be prevalent among the Jewish population. A new
      missense mutation T-->G at nucleotide 576 resulting in V166G was found in an Arab
      Muslim patient. These families may benefit now from pre- and postnatal diagnosis
      by analysis of DNA from blood and amniotic fluid or chorionic villus cells rather
      than liver biopsy. No mutations in the G6Pase gene were detected in two GSD 1b
      patients.

PMID- 7623440
TI  - Variation in mitochondrial DNA levels in muscle from normal controls. Is
      depletion of mtDNA in patients with mitochondrial myopathy a distinct clinical
      syndrome.
AB  - Recent studies have identified a group of patients with cytochrome oxidase (COX)
      deficiency presenting in infancy associated with a deficiency of mtDNA in muscle
      or other affected tissue (Moraes et al 1991). We used a novel approach to compare
      the level of mitochondrial (mtDNA) compared to nuclear DNA in skeletal muscle
      from a group of patients and controls, based on dot blots that were hybridized
      with a mtDNA probe labelled with 35S[dCTP] and a reference nuclear DNA probe
      labelled with [32P]dCTP. The ratio of mtDNA to nuclear DNA varied in samples from
      different muscles of the same individual. Secondly, fetal muscle had very low
      levels of mtDNA compared to nuclear DNA, and data from older controls (cross
      sectional rather than sequential) suggest that this increases rapidly over the
      first 3 months after birth and thereafter more slowly. Four patients with COX
      deficiency had levels of mtDNA that were below the age-specific range defined by
      'normal' quadriceps muscle. The clinical features to two of these patients were
      similar to earlier case reports of mtDNA depletion. In three patients the
      clinical course was relatively benign compared to cases that have previously been
      described. Levels of mtDNA in skeletal muscle from some patients with other forms
      of muscle disease were also found to be low, suggesting that mtDNA depletion,
      possibly related to depletion of mitochondria, may be a relatively non-specific
      response of muscle to various pathological processes. However, there does appear
      to be a distinctive group of young patients with reduced cytochrome oxidase
      activity in muscle, in whom marked mtDNA depletion reflects the primary defect.

PMID- 7623439
TI  - Impaired ketogenesis in fructose-1,6-bisphosphatase deficiency: a pitfall in the
      investigation of hypoglycaemia.
AB  - Intermediary metabolite concentrations were measured in blood during fasting in
      two patients with fructose-1,6-bisphosphatase deficiency. Hypoglycaemia was
      accompanied by markedly raised levels of plasma free fatty acids, without the
      expected degree of ketosis. This suggests that there is secondary impairment of
      ketogenesis in this condition, and could lead to diagnostic confusion.

PMID- 7623441
TI  - An HPLC assay for detection of elevated urinary S-sulphocysteine, a metabolic
      marker of sulphite oxidase deficiency.
AB  - Sulphite oxidase deficiency occurs in man in two forms, as the isolated
      deficiency and as a syndrome of combined molybdoenzyme deficiency. This latter
      pleiotropic condition has as its underlying cause a defect in the synthesis of
      the molybdenum cofactor required for the activity of all molybdoenzymes in
      humans. Difficulties in diagnosis of sulphite oxidase deficiency are often
      encountered. A new method for detection of a key diagnostic metabolite, S
      sulphocysteine, is outlined. The procedure is based on precolumn derivatization
      of urinary amino acids with dimethylaminoazobenzene sulphonyl chloride (Dabsyl
      Cl) and resolution of the modified S-sulphocysteine by reversed-phase HPLC. A
      number of affected patients and control individuals with similar clinical
      symptoms have been studied, and a clear demarcation between the two groups has
      been noted.

PMID- 7623442
TI  - Tyrosinaemia type 1 and glutathione synthetase deficiency: two disorders with
      reduced hepatic thiol group concentrations and a liver 4-fumarylacetoacetate
      hydrolase deficiency.
AB  - Thiol groups are important components of proteins and their oxidation can lead to
      a substantial loss of protein function. Patients with two apparently unrelated
      inborn errors of metabolism, tyrosinaemia type 1 and glutathione synthetase
      deficiency, have been reported to show reduced cell glutathione concentrations.
      We have found that not only glutathione but also protein thiol concentrations are
      reduced in the liver in tyrosinaemia type 1 patients. We also report a case of
      glutathione synthetase deficiency with a substantial deficiency of liver 4
      fumarylacetoacetate hydrolase and provide evidence that glutathione, or some
      small-molecular-weight thiol, is essential for maintaining stability of this
      enzyme in vitro. Our results suggest that the availability of thiol groups may
      modify the phenotype of tyrosinaemia type 1 and that liver 4-fumarylacetoacetate
      hydrolase deficiency may be a secondary complicating factor in some forms of
      glutathione synthetase deficiency.

PMID- 7623443
TI  - Abnormal alpha-aminoadipic acid excretion in a newborn with a defect in platelet
      aggregation and antenatal cerebral haemorrhage.
AB  - alpha-Aminoadipic acid (alpha AA) is an intermediate in lysine metabolism. We
      report a new case with alpha AA excess in urine and plasma, without alpha
      ketoadipic acid, in a full-term male child born to unrelated parents; he
      presented at 24h of life with seizures that failed to respond to phenobarbital,
      clonazepam, and Vigabatrin and death occurred on the 38th day of life. Brain
      imaging suggested antenatal haemorrhage. Small quantities of alpha AA were also
      detected in the blood and urine of both parents and a healthy brother, all three
      of whom exhibited the same defect in platelet aggregation as the deceased child.
      Both parents had decreased levels of plasma neopterin, a finding that might be
      related to the immunodeficiency described in other cases.

PMID- 7623444
TI  - A new neonatal case of N-acetylglutamate synthase deficiency treated by
      carbamylglutamate.
AB  - N-Acetylglutamate synthase (NAGS) deficiency is a rare, autosomal recessive urea
      cycle disease. Its clinical presentation is not different from the other
      hereditary hyperammonaemias. We report a new neonatal case with hyperammonaemic
      coma. A test by carbamylglutamate was performed at 25 days of life. Since then,
      the child was treated by carbamylglutamate three or four times a day with a total
      dose of 80-100 mg/kg per day. Today, the boy is 1 year old. He receives
      carbamylglutamate 200 mg four times a day. He has normal somatic and neurological
      development and good metabolic balance.

PMID- 7623445
TI  - A modified spectrophotometric assay for porphobilinogen deaminase: its
      application in the detection of both carriers and patients with acute
      intermittent porphyria.
AB  - A spectrophotometric method for porphobilinogen deaminase assay in erythrocytes
      is described. This test is determinant for the definite diagnosis of acute
      intermittent porphyria. In the method described, delta-aminolevulinic acid is
      used as substrate. Mercaptoethanol and zinc ions are introduced to maintain delta
      aminolevulinic acid dehydratase in optimal conditions and to guarantee the in
      vitro production of porphobilinogen. An incubation temperature of 45 degrees C
      leads to the production of uroporphyrins, which are measured
      spectrophotometrically at 405 nm, giving reproducible results. The assay can be
      performed easily in any clinical laboratory and is valuable for detecting both
      patients and carriers of acute intermittent porphyria.

PMID- 7623446
TI  - Plasma lysosomal enzyme levels in patients with motor neuron disease.
AB  - beta-Hexosaminidase and acid-alpha-mannosidase were estimated in 17 adult
      patients with motor neuron disease. Normal plasma levels of beta-hexosaminidase
      ((A+B) and A) were found in all patients studied. Plasma acid alpha-mannosidase
      levels were normal in all but two patients with the spinal muscular atrophy type
      of the disorder. In addition, altered biochemical properties of acid alpha
      mannosidase (i.e. Km, thermal stability) were found in the low-activity cases.

PMID- 7623447
TI  - Decreased activity of respiratory-chain enzymes in glutaric aciduria type II.

PMID- 7623449
TI  - Methylmalonic aciduria and urolithiasis in a Chinese boy with untreated
      phenylketonuria.

PMID- 7623448
TI  - Novel mutations in mitochondrial cytochrome b in fatal post partum
      cardiomyopathy.

PMID- 7623450
TI  - Hyperargininaemia: follow-up of a new case.

PMID- 7623451
TI  - Siblings with gamma-glutamyltransferase deficiency.

PMID- 7623452
TI  - Heterogeneity of symptomatology in two male siblings with thymine uraciluria.

PMID- 7623453
TI  - Molybdenum cofactor deficiency associated with Dandy-Walker malformation.

PMID- 7623454
TI  - Severe neonatal galactose-dependent disease with low-normal epimerase activity.

PMID- 7623456
TI  - Bone marrow transplantation in Hunter syndrome.

PMID- 7623455
TI  - Factor XI and phosphorylase b kinase deficiency.

PMID- 7623457
TI  - Another unusual case of fucosidosis.

PMID- 7623458
TI  - Morquio disease in a patient diagnosed as having Perthes disease for 38 years.

PMID- 7623459
TI  - Molecular defect of caprine N-acetylglucosamine-6-sulphatase deficiency. A single
      base substitution creates a stop codon in the 5'-region of the coding sequence.

PMID- 7623460
TI  - Importance of sequence analysis in NARP syndrome.

PMID- 7623461
TI  - Ketonuria and medium-chain acyl-CoA dehydrogenase deficiency.

PMID- 7623462
TI  - Effects of moderate dose alcohol on visual contrast sensitivity for stationary
      and moving targets.
AB  - OBJECTIVE: Contrast sensitivity involves distinguishing threshold luminance
      differences and is usually assessed using static sine-wave gratings over a range
      of different spatial frequencies. The purpose of this study was to determine the
      effects of various levels of acute alcohol intoxication on contrast sensitivity
      to stationary and moving sine-wave gratings. Moving gratings required the
      subjects to make pursuit eye movements. A secondary goal was to investigate
      whether any alcohol-related effects were associated with any measures of
      intoxication. METHOD: Male volunteers (N = 8) participated in three
      counterbalanced, double-blind, testing sessions (low alcohol, moderate alcohol
      and placebo) plus a control session with no beverage. Breath alcohol
      concentration and two subjective measures of intoxication were measured for each
      subject. Static and dynamic contrast sensitivity were determined for
      electronically generated sine-wave gratings that were either stationary or
      traveled in a circular path with a diameter of 9 cm (3.7 degrees) at 51.7 rpm,
      thus requiring the subject to make smooth pursuit eye movements. RESULTS: The
      mean blood alcohol concentration measured in the moderate alcohol condition was
      0.043% and in the low alcohol condition 0.011%. Moderate dose alcohol consumption
      significantly impaired both static and dynamic contrast with a greater effect for
      moving targets. CONCLUSIONS: Objective and subjective measures of intoxication
      were unrelated to the alcohol-related losses in contrast sensitivity. Although
      most states currently prohibit driving with BACs of 0.08-0.10%, the present data
      indicate reliable visual impairment at approximately half of that level (.44%).

PMID- 7623463
TI  - The role of a substance abuse consultation team in a trauma center.
AB  - OBJECTIVE: Trauma is a leading cause of morbidity and mortality in the U.S., and
      substance abuse makes an enormous contribution to this problem as well as to the
      increased cost of health care. A substance abuse consultation (SAC) team was
      developed to evaluate and intervene with trauma victims who are suspected of
      having problems with alcohol and/or other drugs. This study was undertaken to
      determine the effectiveness of this service. METHOD: This study is a
      retrospective review of 100 consecutive trauma admissions who were felt to be at
      high risk for substance abuse and were referred to the SAC team for evaluation
      and intervention. This study was undertaken in a tertiary care teaching hospital
      in a cooperative effort between the trauma center and the addictions program.
      RESULTS: All 100 patients were diagnosed with psychoactive substance use
      disorders and 78 were referred for alcohol and other drug rehabilitation. Of
      these patients, 62% accepted a referral for drug and alcohol treatment.
      CONCLUSIONS: From these preliminary data, it appears that a SAC team may be
      effective in intervening with hospitalized trauma patients who have alcohol and
      other drug problems.

PMID- 7623464
TI  - Alcohol use among HMO patients in the emergency room, primary care and the
      general population.
AB  - OBJECTIVE: Although heavy drinking and alcohol-related problems are overpresented
      among patients seen in some primary care settings compared to the general
      population, it is not known whether those seen for noninjury problems in
      emergency rooms (ERs) are similar in demographic and drinking characteristics to
      those seen in primary care clinics. Nor do we know whether alcohol-related
      problems are over-represented in both of these settings compared to the general
      population when equal access to health care services is provided, as by
      membership in the same HMO. Reported here are data from a single northern
      California health maintenance organization (HMO). METHOD: Probability samples of
      noninjured patients seen in the ERs of the HMO (n = 579) are compared on
      demographic characteristics and drinking patterns and problems to those seen in
      the primary care clinics of the same HMO (n = 295) and to those in the general
      population of the same county who reported membership in the HMO (n = 737).
      RESULTS: No differences in drinking patterns, alcohol-related problems or gender
      or age distribution were found between the clinic patients and the noninjured ER
      patients. Both the noninjured ER patients and the clinic patients were less
      likely to report heavy and problem drinking, or treatment for an alcohol-related
      problem during the last year, as compared to those in the general population.
      CONCLUSIONS: The data from this HMO study suggest that noninjured patients seen
      in these particular emergency rooms resemble those seen in primary care, and
      that, contrary to the commonly held belief that alcohol-related problems are
      overrepresented in primary care, primary care patients in this HMO population may
      be less likely to be problem drinkers than those in the general population from
      which they come.

PMID- 7623465
TI  - Validity of the CAGE questionnaire in screening for alcohol dependence in a walk
      in (triage) clinic.
AB  - OBJECTIVE: This study assessed the value of the CAGE questionnaire in detecting
      alcohol dependence in the walk-in (triage) clinic of an acute care Veterans
      Affairs hospital. METHOD: Male veterans (N = 1,667) attending the walk-in clinic
      were asked several questions relating to whether they were current drinkers, were
      seeking alcohol treatment, and whether they had been hospitalized for treatment
      of alcoholism. Those who were current drinkers, were not seeking alcohol
      treatment and had not been hospitalized for alcohol treatment were given the CAGE
      questionnaire followed by a diagnostic interview utilizing DSM III-R criteria to
      determine the presence or absence of a lifetime diagnosis of alcohol dependence.
      RESULTS: The diagnostic interview revealed a prevalence rate for alcoholism of
      22% in this clinic population. The CAGE scale, when used with one or more yes
      responses indicating a positive response, achieved a sensitivity of 86% and
      specificity of 93% when using the diagnostic interview as the criterion standard.
      CONCLUSIONS: This study adds to the evidence that the CAGE questionnaire is an
      effective, efficient, easily used screening instrument for the detection of
      alcohol dependence in a clinical setting.

PMID- 7623466
TI  - Using the CAGE to screen for drinking-related problems in college students.
AB  - OBJECTIVE: As a brief alcohol screening instrument the CAGE has demonstrated a
      high degree of accuracy in identifying problem drinkers among adults. However,
      some studies have questioned its screening accuracy within a college population.
      The research presented in this article contains the results of two additional
      studies that examined the ability of the CAGE to identify problem drinkers within
      a college student population. METHOD: In both 1988 and 1992 a questionnaire of
      various drinking practices, including CAGE items, was mailed to a random sample
      of 1,000 students at a large midwestern university (response rate: 58.2%, 1988;
      49.8%, 1992). Using identical problem-drinking criteria, sensitivity, specificity
      and positive predictive values at various cutoff scores of the CAGE were
      calculated for both sets of data and for gender. RESULTS: At the recommended CAGE
      cutoff score of > 2 for a positive test the sensitivity and positive predictive
      values (PPV) were slightly higher for the 1992 sample. The PPV values at that
      cutoff score were 46% (1988) and 49% (1992) and 48% for the combined data. In
      both samples the screening values were lower for women. CONCLUSIONS: These data
      from both surveys do not support the CAGE as a screening measure for problem
      drinking with this population. It appeared to be less accurate with women
      although that conclusion should be tempered by the fact that there was a
      relatively low percentage of problem drinkers found among women.

PMID- 7623467
TI  - Heavy drinking contexts and indices of problem drinking among college students.
AB  - OBJECTIVE: Heavy drinking among college students carries with it the risk of
      adverse consequences. This study explored the relationship between alcohol
      related problems and the social-emotional contexts of drinking in college
      students. METHOD: Undergraduate volunteers (N = 139; 61% female; 27% minority)
      completed an assessment of drinking patterns, the short form of the Inventory of
      Drinking Situations (IDS-42) and an alcohol problems index. RESULTS: Heavy
      drinkers drank more, relative to light/moderate drinkers, in five of the eight
      situations assessed by the IDS-42. Several IDS-42 subscales correlated highly
      with the number of alcohol-related problems. Subjects identified by their extreme
      scores on the IDS-42 reported more alcohol problems, greater maximum quantities
      consumed and more frequent intoxication. CONCLUSIONS: The IDS-42 can identify the
      contexts in which heavy drinking occurs and individuals who are likely to
      experience alcohol problems.

PMID- 7623468
TI  - Predicting adolescents' intentions to drink alcohol: outcome expectancies and
      self-efficacy.
AB  - OBJECTIVE: This article examines the relationship between intention to drink
      alcohol, alcohol outcome expectancies and alcohol-related self-efficacy among
      Norwegian adolescents. The relationship of expectancies, intention and self
      efficacy was assessed for respondents of different ages and different drinking
      experience. METHOD: Data were collected from all seventh and ninth graders in 12
      randomly selected schools in Norway. The self-administered questionnaire
      contained a short version of the Alcohol Expectancy Questionnaire for Adolescents
      and measures of intentions to drink in the next 12 months, current alcohol use
      and alcohol-related self-efficacy (e.g., ability to refuse alcohol). RESULTS:
      Results showed that both alcohol outcome expectancies and previous experience
      with alcohol were related to intentions to drink alcohol in the near future.
      Drinking experience had a larger impact than a 2-year age difference on the
      associations between alcohol outcome expectancies, alcohol-related self-efficacy
      and intention to drink. A significantly higher proportion of adolescents with
      drinking experience reported positive alcohol expectancies, poor alcohol-related
      self-efficacy and strong intention to drink alcohol than did those adolescents
      without drinking experience. CONCLUSIONS: Personal drinking experience was a
      stronger predictor of drinking intentions than was age. Still, both alcohol
      outcome expectancies and alcohol-related self-efficacy are significant predictors
      of intention to drink among both seventh and ninth graders, independent of
      previous drinking experience. This study indicates that postponing the onset of
      alcohol experimentation could be a major goal in primary alcohol prevention among
      adolescents, although longitudinal confirmation of these results is needed.

PMID- 7623469
TI  - The alcoholics in treatment HIV risk (ATRISK) study: gender, ethnic and
      geographic group comparisons.
AB  - OBJECTIVE: This study attempted to identify alcoholic inpatients as a population
      at elevated risk for HIV infection in comparison with other groups. Modes of risk
      across gender, ethnic and geographic subgroups were explored in order to guide
      targeted preventive efforts in the future. METHOD: Structured interviews were
      conducted with 802 alcoholic inpatients (481 males, 321 females) in New York City
      and western New York State. RESULTS: Measures of sexual risk behavior indicated
      low rates of condom use and high rates of multiple or nonprimary sex partners.
      Trading sex for drugs or money was common. Injection drug use was reported by
      nearly one-fifth of these patients. Most subjects (59.9%) reported at least one
      sexually transmitted disease. Self-reported HIV status yielded a seroprevalence
      rate of 6.7% among those who knew their HIV status. CONCLUSIONS: Findings
      indicated rates of HIV infection and associated risk behaviors similar to, and in
      some instances exceeding, those of other high-risk subpopulations. Subgroup
      differences indicated unique patterns of risk behavior across gender, ethnic and
      geographic subgroups. Findings are discussed with regard to prevention and
      treatment implications of high-risk behaviors among alcoholic inpatients.

PMID- 7623470
TI  - The prevalence of major anxiety disorders in relatives of alcohol dependent men
      and women.
AB  - OBJECTIVE: The relationship between alcohol dependence and lifelong major anxiety
      disorders is complex. The literature indicates a close association between
      anxiety symptoms and drinking behavior. However, it is difficult to determine
      whether the anxiety conditions are lifelong disorders or if they represent
      temporary organic conditions related to alcohol intoxication and withdrawal. One
      approach to understanding more about the relationships between alcohol dependence
      and major anxiety disorders is to observe the rate of anxiety-related diagnoses
      in close relatives of alcoholics. This approach evaluates whether alcoholism and
      major anxiety disorders might share a common genetic basis. METHOD: The data
      presented here describe the rates of four major anxiety disorders in 591
      interviewed first-degree relatives of alcohol dependent men and women. The data
      were gathered through face-to-face structured standardized interviews. RESULTS:
      The analyses reveal that after focusing on DSM-III-R anxiety disorders,
      controlling for the potential presence of temporary organic conditions in the
      subject and considering the impact of assortative mating in their parents, the
      life-time risk for panic disorder in close biological family members of
      alcoholics is 3.4%; for agoraphobia, 1.4%; for social phobia, 2.3%; and for
      obsessive-compulsive disease, 1.4%. CONCLUSIONS: These data do not indicate an
      exceptionally high rate of anxiety disorders among close relatives of alcoholics.
      While other mechanisms might contribute to relationship between alcoholism and
      major anxiety disorders, the results do not support evidence of a common genotype
      for the two disorders.

PMID- 7623471
TI  - Temperament and personality typologies in adult offspring of alcoholics.
AB  - OBJECTIVE: The primary goal of the present study was to derive temperament and
      personality typologies among adult offspring of alcoholics and their controls in
      two separate samples. Additional aims were to examine the relation between
      temperament/personality typologies and drinking behaviors, and to explore the
      effect of antisocial behavior on this relation. METHOD: The first sample assessed
      consisted of middle-aged adult men and women (82 offspring of alcoholics and 72
      controls), whereas the second sample included only young adult men who were
      oversampled for antisocial personality disorder (44 offspring of alcoholics and
      47 controls). RESULTS: Two distinct temperament typologies emerged across both
      samples. One typology ("Cluster 1") was characterized by high levels of harm
      avoidance and pessimism, and low levels of sensation and self-esteem whereas the
      other typology ("Cluster 2") was characterized by the reverse of these
      characteristics. Cluster 1 individuals also tended to exhibit many
      characteristics of the "difficult temperament", whereas Cluster 2 individuals did
      not. In addition, Cluster 1 individuals were found to consume more alcohol and to
      have higher MAST scores than Cluster 2 individuals. However, when antisocial
      behavior was considered, the typologies were unrelated to any of the indices of
      drinking behaviors in both samples. CONCLUSIONS: The temperament typologies that
      emerged in the present study are consistent with the literature. More
      importantly, these typologies were found across two separate samples and among
      both offspring of alcoholics and offspring of nonalcoholics. Finally, the
      relationship between temperament/personality typologies and drinking behaviors
      was generally nonsignificant once antisocial behavior was considered.

PMID- 7623472
TI  - Progression of alcohol consumption across the drinking career in alcoholics and
      social drinkers.
AB  - OBJECTIVE: To document and compare the changes in alcohol intake over the
      drinking career in alcoholic (n = 273) and social (n = 152) drinkers and to
      relate the changes to age and to the prevalence of morning drinking. METHOD:
      Lifetime alcohol intake was assessed in face-to-face interviews by asking
      subjects to report drinking patterns during different "phases" of their drinking
      careers, beginning with the onset of regular drinking and continuing up to the
      present. RESULTS: Alcohol consumption began at higher quantities and higher
      frequencies in alcoholics (prealcoholics) and rapidly escalated within a few
      years to values well out of the range of moderation. The alcohol intake of social
      drinkers at the beginning phase was only about 70% that of alcoholics. In
      contrast to alcoholics, the alcohol intake of social drinkers remained relatively
      constant across subsequent drinking phases at about three to four drinks per
      drinking occasion, with only a slight increase in the frequency of drinking over
      sequential drinking phases. The relationship of total alcohol consumption to age
      in alcoholics was described best by a curvilinear function, with alcohol
      consumption peaking near age 40. CONCLUSIONS: Gender differences in consumption
      were decreased with adjustment for body water content. The higher initial alcohol
      intakes in alcoholics may reflect a lower sensitivity to the intoxicating effects
      of alcohol, or, alternatively, a greater ability of alcoholics to develop
      tolerance. The high prevalence of morning drinking in alcoholics compared to
      social drinkers reinforces the usefulness of morning drinking as a diagnostic
      tool, particularly for female alcoholism.

PMID- 7623473
TI  - Integrated outpatients treatment for medically ill alcoholic men: results from a
      quasi-experimental study.
AB  - OBJECTIVE: This report documents the findings of a quasi-experimental study of a
      new approach to treating medically ill alcoholics. The intervention, the Alcohol
      Related Disorders (ARD) Clinic, consists of concurrent alcohol treatment and
      medical care delivered by an interdisciplinary team in an outpatient medical
      clinic at the Minneapolis Veterans Affairs Medical Center (MVAMC). METHOD: We
      compared 50 ARD patients with 50 patients who met eligibility for the clinic, but
      had to be referred elsewhere because the clinic was full at the time (referred
      patients). Referred patients received medical care in other MVAMC clinics or in
      the community. RESULTS: During the 2-year follow-up period, ARD patients returned
      for outpatient visits over three times as often as referred patients (p < .001).
      More referred patients received no follow-up care at MVAMC (p < .01). ARD
      patients had more frequent (p < .05) but briefer (p < .01) hospitalizations.
      Almost twice as many referred (32%) as ARD patients (18%) died during the follow
      up period. Referred patients ranged from 1.18 times less likely to 5.03 times
      more likely to die during follow-up than those in the ARD group (p = .11). ARD
      patients lived for an average of 82 days longer than referred patients, and each
      ARD clinic visit in the second follow-up year predicted an additional 3.5 days
      lived (p < .01). CONCLUSIONS: Integrated outpatient treatment for medically ill
      alcoholics appears to improve outpatients follow-up and alter patterns of
      hospitalization when compared with standard approaches. Two-year mortality may
      have been reduced as a result.

PMID- 7623474
TI  - Alcohol use in combination with cocaine, heroin and methadone by medical examiner
      cases.
AB  - OBJECTIVE: The purpose of this review of all appropriate, available medical
      examiner (ME) studies is to provide information on cases with positive
      toxicologies for cocaine, morphine (the heroin metabolite) and methadone that
      have positive blood or brain alcohol concentrations (BACs). METHODS: Criteria for
      inclusion of U.S. ME studies in this review are (1) at least 20 cases with a
      positive toxicology for cocaine, morphine or methadone and (2) BAC test findings
      according to specific drug positivity. Only 19 studies conducted from 1969 to
      1992 met these criteria; most studies reviewed were not included primarily
      because of their failure to present or link available BAC test findings with
      positive toxicologies for these other drugs. RESULTS: The BAC-positive ranges
      were similar for cocaine and heroin. In reports on both heroin and methadone or
      on all three drugs, heroin-positive cases had the highest proportions and
      methadone-positive cases had the lowest proportions with positive BACs.
      CONCLUSIONS: Published data confirm the substantial presence of alcohol in
      combination with cocaine, heroin and methadone among ME cases. Future ME studies
      should endeavor to link BAC and toxicology findings for other drugs according to
      drug-induced or drug-related manner of death. These data would advance our
      knowledge about the role of alcohol in drug deaths and provide additional
      information on substance abuse trends.

PMID- 7623475
TI  - Behavior and perceptions related to drink-driving among an international sample
      of company vehicle drivers.
AB  - OBJECTIVE: The study examined reported behavior, perceptions and attitudes
      related to drink-driving among company vehicle drivers located across eight
      countries. An additional aim of the research was to identify important predictors
      of drink-driving. METHOD: A cross-sectional mailshot questionnaire survey was
      undertaken on all drivers of company vehicle identified by the collaborating
      companies. Responses to items concerning reported drink-driving, perceived
      consumption limits, perceived risk and reported restraint were examined for a
      total of 600 male drivers, representing an overall response rate of 55%. RESULTS:
      Driving after any alcohol consumption was found to be relatively common across
      most of the sample, while driving when over the legal limit at least once in the
      previous 12 months was reported by approximately one-third of the drivers.
      Multiple regression analysis indicated that the strongest predictors of reported
      drink-driving behavior were associated with perceived limits of personal alcohol
      consumption and a "moral attachment" to non-drink-driving associated with alcohol
      consumption restraint. This general prediction model seemed to be relatively
      consistent across the different national groups. CONCLUSIONS: The results suggest
      that longer term cognitive components of decision making such as "moral
      attachment" may form fundamental elements in the decision to drive after
      excessive drinking. It was suggested that company-based policies and programs may
      have a useful role in promoting safer driving practices, particularly in relation
      to driving after drinking.

PMID- 7623476
TI  - Differentiating "bad drivers" with and without a DWI.
AB  - OBJECTIVE: Risk factors for driving while intoxicated (DWI) are still largely
      unknown. The aim of this study was to determine the risk factors, other than
      multiple vehicle-related violations, that identify a group of bad drivers at risk
      of subsequent DWI violations. METHOD: A retrospective cohort study was conducted
      of drivers with multiple vehicle-related violations who completed a questionnaire
      on driving and personal characteristics (N = 253). RESULTS: Thirty-six variables
      were found associated with a 1.8- to 6.3-fold increased risk of subsequent DWI in
      the following categories: driving behavior, drinking behavior, history of
      physical trauma, alcohol-related expectancies and family history. CONCLUSIONS: A
      screening system could be incorporated in DWI prevention programs to target high
      risk groups.

PMID- 7623477
TI  - Alcohol warnings in TV beer advertisements.
AB  - OBJECTIVE: Mandated warnings are among the few steps Congress has taken to
      influence the use of legal substances such as alcohol. The usefulness of such
      warnings in discouraging abuse of alcohol is, however, controversial. This study
      examines the impact of televised warnings on probable antecedents of belief
      change not examined in previous research: confidence in beliefs about beer risks
      or benefits, and cognitive responses to the advertisements. METHOD: The present
      study (N = 75 male and female college students) tests four of the warnings
      recommended in Senate Bill 674 (1993--the "Thurmond bill") edited into randomly
      sampled television beer advertisements, using a between-subjects treatment-and
      control experimental design. The four advertisements or advertisement/warning
      pairs were counterbalanced and analyzed as a repeated measures factor. RESULTS:
      The study indicated, as hypothesized, that subjects exposed to warnings tended to
      have less confidence in their generally skeptical assessments of beer risks--a
      likely precursor to belief change in resistant populations. Repeated exposure to
      the advertisements alone also appeared to lead to increased confidence in
      generally positive assessments of beer benefits, whereas repeated exposure to
      warnings led to decreased confidence in such assessments. Repeated exposure to
      warnings also may have primed negative reactions to subsequent beer
      advertisements. CONCLUSIONS: These results suggest mechanisms by which alcohol
      warnings may over time influence beliefs. Measures used here may serve as useful
      criterion variables in future studies on warnings. Further attention to
      optimizing warning content and presentation is recommended.

PMID- 7623478
TI  - Antimicrobial activity of Cassia alata from Malaysia.
AB  - Ethanolic extract of Cassia alata leaves was investigated for its antimicrobial
      activities on several microorganisms including bacteria, yeast, dermatophytic
      fungi and non-dermatophytic fungi. In vitro, the extract exhibited high activity
      against various species of dermatophytic fungi but low activity against non
      dermatophytic fungi. However, bacterial and yeast species showed resistance
      against in vitro treatment with the extract. The minimum inhibitory concentration
      (MIC) values of the extract revealed that Trichophyton mentagorphytes var.
      interdigitale, Trichophyton mentagrophytes var. mentagorophytes, Trichophyton
      rubrum and Microsporum gypseum had the MIC of 125 mg/ml, whereas Microsporum
      canis had the MIC of 62.5 mg/ml. The inhibition can be observed on the
      macroconidia of Microsporum gypseum which resulted in structural degeneration
      beyond repair. The mechanism of inhibition can be related to the cell leakage as
      observed by irregular, wrinkle shape and loss in rigidity of the macroconidia.

PMID- 7623479
TI  - New contributions to the ethnopharmacology of Spain.
AB  - In the course of an ethnobotanical research project carried out in the Province
      of Granada (Southern Spain), 267 taxa have been catalogued as being used in folk
      medicine. Based on the literature consulted, phytotherapeutic use for 34 of these
      was recorded for the first time.

PMID- 7623480
TI  - Toxicological studies on the ethanolic extract of Crotalaria juncea seeds in
      rats.
AB  - The effect of the ethanolic extract of Crotalaria juncea Linn. (Leguminosae)
      seeds has been assessed on liver, kidney, spleen and adrenals of adult rats.
      Results revealed that its administration at a dose of 200 mg/kg caused
      significant alterations. Wet weight of the organs was reduced. Protein and
      glycogen contents in all the organs were decreased significantly, whereas, the
      activity of acid and alkaline phosphatase was increased. Histology revealed
      remarkable disintegration necrosis and degeneration in the liver. Renal tubular
      cells showed degeneration and exfoliation. Adrenals showed hypertrophy in the
      region of zona glomerulosa. In the spleen the number of megakaryotic cells and
      lymphocytes was increased. Administration of the extract therefore not only
      damaged the liver but other vital organs too were also affected.

PMID- 7623482
TI  - Crude extracts of hepatoprotective plants, Solanum nigrum and Cichorium intybus
      inhibit free radical-mediated DNA damage.
AB  - The presence of plant extracts of Solanum nigrum and Cichorium intybus in the
      reaction mixture containing calf thymus DNA and free radical generating system
      protect DNA against oxidative damage to its deoxyribose sugar moiety. The effect
      was dependent on the concentration of plant extracts. However, the effect of
      Cichorium intybus was much pronounced as compared to the effect of Solanum
      nigrum. These studies suggest that the observed hepatoprotective effect of these
      crude plant extracts may be due to their ability to suppress the oxidative
      degradation of DNA in the tissue debris.

PMID- 7623483
TI  - Biological activities of a Turkish medicinal plant, Prangos platychlaena.
AB  - Prangos platychlaena has been used in traditional medicine in eastern Turkey. It
      stops bleeding and heals the scars when applied externally. When the isolated
      coumarins were tested against bacterial strains, only a slight activity was
      obtained.

PMID- 7623481
TI  - Antibacterial activity of a substance produced by the fungus Pycnoporus
      sanguineus (Fr.) Murr.
AB  - A fraction obtained from the culture fluids of Pycnoporus sanguineus fungus was
      shown to contain a compound with biological activity against strains of
      Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella
      typhi, Staphylococcus aureus and members of the genus Streptococcus. The fraction
      was clearly more active on Gram-positive cocci than on Gram-negative bacilli.

PMID- 7623484
TI  - Anticonvulsant activity of Casimiroa edulis in comparison to phenytoin and
      phenobarbital.
AB  - An aqueous extract of Casimiroa edulis leaves was tested in adult male Wistar
      rats for anticonvulsant activity utilizing two models of experimental epilepsy:
      maximal electroshock seizure (MES) and subcutaneously injected metrazole (METsc).
      Single dose of 100 mg/kg C. edulis vacuum dried aqueous extracts (VDA) orally
      administered to experimental animals elicited 50% and 70% abolition of MES and
      METsc-induced seizures, respectively. Two firmly established antiepileptic drugs
      in human therapy, phenytoin (PHT) and phenobarbital (PB), abolished 90% of MES
      induced seizures, whereas an 80% and 100% absence of clonic seizures was attained
      in METsc test, correspondingly. The seizure abolition observed in C. edulis VDA
      treated rats was comparable with the anticonvulsive pattern exhibited by PHT and
      PB. These results suggest that potencially antiepileptic compounds are present in
      C. edulis extracts that deserve the study of their identity and mechanism of
      action.

PMID- 7623486
TI  - Effect of Herniaria hirsuta and Agropyron repens on calcium oxalate urolithiasis
      risk in rats.
AB  - The effects on the calcium oxalate urolithiasis urinary risk factors of Herniaria
      hirsuta L. (Carryophyllaceae) and Agropyron repens L. (Gramineae), in herb
      infusion form, combined with different diets (standard, high glucidic, high
      protein) have been studied using Wistar rats. From this study it is deduced that
      the possible effects of the A. repens infusion can not be assigned to any
      positive effects on the main urolithiasis risk factors. The tentative
      antilithiasic effects of the H. hirsuta infusion clearly depends on the diet.
      Thus, a clear increase in the citraturia was only detected when such infusion was
      administered with the high protein diet.

PMID- 7623485
TI  - Analgesic effect of Dioclea grandiflora constituents in rodents.
AB  - An aqueous fraction and dioclein (5,2',5'-trihydroxy-6,7-dimethoxyflavanone)
      obtained from the ethanolic extract of the Dioclea grandiflora were tested for
      their analgesic effect in mice and rats employing acetic-induced writhing and
      tail flick tests, respectively. When administered intraperitoneally the two
      agents exhibited significant analgesic effects. The activity of both dioclein and
      aqueous fraction apparently involves an opiate-like mechanism, since their
      analgesic action was attenuated by naloxone pretreatment.

PMID- 7623487
TI  - Isolation of cholinergic active ingredients in aqueous extracts of Mareya
      micrantha using the longitudinal muscle of isolated guinea-pig ileum as a
      pharmacological activity marker.
AB  - In our attempt to isolate the pharmacologically active ingredients in the aqueous
      extracts of Mareya micrantha, we have selected the contractions of the
      longitudinal muscle of the isolated guinea-pig ileum preparation as a
      pharmacological marker to monitor retention of pharmacological activity during
      the chromatographic separation. The aqueous extracts of Mareya micrantha elicited
      concentration-dependent contractions of the preparation. The maximum response
      elicited by the aqueous extracts was 50% of the maximum response elicited by the
      maximum dose of acetylcholine (ACh), 10(-7) M. Mepenzolate (10(-8)-10(-5) M), a
      specific muscarinic receptor antagonist, similarly antagonized contractions
      elicited by the aqueous extracts suggesting that the cholinergic ingredient(s) in
      the extract are acting at the muscarinic receptors of the preparation. Fraction 2
      4, which was separated from the aqueous extracts by Sephadex gel chromatography,
      dose-dependently elicited contractions of the preparation. The maximum response
      was 80% of the maximum response elicited by the maximum dose of ACh suggesting
      that separation has enhanced the cholinergic activity of the content in the
      extract.

PMID- 7623488
TI  - Anti-hyperglycemic effect of black tea (Camellia sinensis) in rat.
AB  - Investigations were carried out to evaluate the effect of the hot water extract
      of black tea (Camellia sinensis (L.) O. Kuntze (Theaceae) on streptozotocin (STZ)
      induced diabetes in rats. The extract significantly reduced the blood glucose
      level and was found to possess both preventive and curative effects on
      experimentally produced diabetes in rats. The study reveals that, like green tea,
      black tea also possesses antidiabetic activity.

PMID- 7623489
TI  - [Morbidity and mortality associated with chronic viral hepatopathy in patients
      infected with the human immunodeficiency virus].
AB  - BACKGROUND: Hepatitis B, C and D virus infection is frequent in HIV-infected
      individuals, particularly in drug addicts. However, chronic liver disease of
      viral etiology has been little studied in AIDS. METHODS: The impact of infection
      by hepatotropic viruses on hospital morbidity/mortality was analyzed in a group
      of HIV positive (HIV+) patients over the period from October 1991 to April 1994.
      RESULTS: Viral liver disease was the cause of hospitalization in 94 (8.6%) out of
      1,082 HIV+ patient admissions. Only 4 admissions were for severe or fulminant
      cases of acute viral hepatitis. Complicated (gastrointestinal bleeding, and
      spontaneous bacterial infection) or decompensated (ascites, jaundice and
      encephalopathy) viral liver disease was the diagnosis in the 90 remaining cases.
      Death directly associated to liver diseases was observed in 9 (9.5%) of these
      patients, globally representing 4.3% (9 out of 207) of the causes of hospital
      mortality during the study period, and the fifth in order of frequency. Hospital
      stay was significantly longer in patients admitted for decompensated or
      complicated chronic viral liver disease in comparison with the remaining patients
      (27.9 +/- 9 versus 18.4 +/- 8 days) (p < 0.05). Infection by the hepatitis C
      virus was observed in 88% (80 out of 90) of the hospital admissions for chronic
      liver disease although half presented coinfection by B or delta viruses.
      CONCLUSIONS: Chronic liver disease of viral etiology, mainly by the hepatitis C
      virus, represents an important cause of hospital morbidity and mortality in
      Spanish HIV+ patients.

PMID- 7623490
TI  - [The Kveim-Siltzbach test in sarcoidosis].
AB  - BACKGROUND: The Kveim-Siltzbach test has been widely used in the diagnosis of
      sarcoidosis. This reactive is currently available in the authors' hospitals.
      Previous experience with this test in the same centers was reviewed to know its
      diagnostic usefulness. The present is the first series described in Spain.
      METHODS: From 1977 to 1988 the Kveim-Siltzbach test was performed in 79 patients
      diagnosed or suspected of having sarcoidosis. The study was carried out as
      cooperation of the validation process of sarcoid spleen suspensions (lots K12,
      K12 1/2, K32, K41, K42, K42 1/2 and K50 of the Colindale antigen) prepared in the
      Standards Laboratory for Serological Reagents in the Royal Brompton Hospital in
      London. RESULTS: The results of test positivity were determined following the
      criteria established by Siltzbach. The global sensitivity of the Kveim-Siltzbach
      test was 78% (CI 95% = 67.8-86.9). Positivity ranged from 84% in subacute
      sarcoidosis to 61% in chronic sarcoidosis (p = 0.08). Likewise, it was higher in
      patients with radiologic stage I (84%) and II (81%) with respect to stage III
      (62%) or the cases with exclusive extrathoracic sarcoidosis (stage 0) (57%) (p =
      0.11). No association was found between the Kveim-Siltzbach test positivity and
      the elevation in serum values of the angiotensin-converting enzyme (p = 0.575).
      CONCLUSIONS: In the present study the Kveim-Siltzbach test showed high
      sensitivity in the diagnosis of sarcoidosis. This fact, together with the high
      specificity observed in other studies, makes the test a very useful tool for the
      non-invasive diagnosis of sarcoidosis.

PMID- 7623492
TI  - [The transplantation of hemopoietic progenitors in chronic myeloid leukemia: why,
      how and when?].

PMID- 7623491
TI  - [The diagnosis and prevalence of locus CMT1A duplication in Charcot-Marie-Tooth
      disease type 1].
AB  - BACKGROUND: The Charcot-Marie-Tooth (CMT) disease or hereditary motor-sensitive
      neuropathy (HMSN) is the most frequent hereditary neuropathy. The demyelinated or
      type 1 form (CMT1) is the most frequently presented, commonly being of a dominant
      autosomic inheritance. CMT1 is heterogeneous genetically and the subjacent
      mutation found in most of the cases is a duplication of 1,500 kb in the CMT1A
      locus of chromosome 17p11.2. The aim of the present study was to determine the
      prevalence of CMT1A duplication in patients with CMT1 and evaluate its usefulness
      as a biological diagnostic marker. METHODS: The study was carried out in a group
      of patients with HMSN who were not related, and were distributed according to the
      following diagnostic categories: CMT1 (n = 49), CMT2 (n = 9), untyped CMT (n =
      11) and Dejerine-Sottas (DS) disease (n = 4). To detect three alleles confirming
      the presence of duplication the DNA of the patients was analyzed with four
      polymorph markers, VAW409R3a, RM11-GT, VAW412R3HEc and EW401HE localized in the
      CMT1A locus. RESULTS: CMT1A duplication was found in 68.7% of the patients with
      CMT1 and in 27.2% of untyped CMT patients. None of the individuals in the CMT2
      and DS categories showed duplication. Cases pertaining to families with dominant
      autosomic inheritance and genetically sporadic cases were confirmed to show a
      high prevalence of duplication, being of 83.3% and 85.7%, respectively.
      CONCLUSIONS: Duplication of the CMT1A locus is the most prevalent mutation found
      in Charcot-Marie-Tooth type 1 disease. It is a specific mutation of this disease
      among the different forms of hereditary motor-sensitive neuropathy. This mutation
      is useful as a biological marker in the diagnosis of these neuropathies.

PMID- 7623493
TI  - [Intraoral Kaposi's sarcoma. Its epidemiology and the etiology controversies].

PMID- 7623494
TI  - [A left iliac psoas abscess in a patient treated for pulmonary tuberculosis].
AB  - The case of an 81-year-old ex-smoker male diagnosed with chronic bronchitis and
      undergoing treatment for pulmonary tuberculosis who presented a left iliac psoas
      abscess of torpid evolution is herewith reported. The detection of aerobic,
      anaerobic, fungal and mycobacterial microorganisms was repeatedly negative and
      was finally found to be an abscessed metastasis of epidermoid lung cancer. The
      aspects related to psoas abscess, muscular metastasis of bronchogenic carcinoma
      and the association between tuberculosis and lung cancer are discussed.

PMID- 7623496
TI  - [Endothelin, nitric oxide and the control of vascular tone: their
      physiopathological significance in liver cirrhosis].

PMID- 7623495
TI  - [ROC curves in the evaluation of diagnostic tests].

PMID- 7623497
TI  - [Bilateral apical empyema secondary to a spinal epidural abscess].

PMID- 7623498
TI  - [Immunity to diphtheria in young adults in Spain].

PMID- 7623499
TI  - [Transdermal scopolamine patches and anisocoria].

PMID- 7623500
TI  - [Malaria in parenteral drug abuse patients].

PMID- 7623501
TI  - [Pneumonia and bone marrow infection with Rhodococcus equi in an AIDS patient].

PMID- 7623502
TI  - [Predictive factors of surgical infection in heart surgery].
AB  - BACKGROUND: Deep infection of the surgical site in cardiac surgery may lead to
      very severe complications. There is controversy as to the importance which
      different factors may have in the incidence of this complication. The aim of this
      study was to determine the importance of determined factors on the risk of deep
      infection of the surgical site. METHODS: A retrospective study of 1,127 patients
      submitted to cardiac surgery from 1989 to 1991 was performed. The factors
      associated to the development of deep surgical infection were determined by
      univariant analysis. A multiple logistic regression model was designed to
      identify the factors independently associated to the risk of infection. The
      morbidity of surgical infection attributable to prolonged preoperative stay was
      calculated. RESULTS: Of the numerous factors associated to risk of surgical site
      infection on univariant analysis, only five were independently associated to risk
      of infection on multivariant analysis: prolonged preoperative stay (OR = 2.4 [1.1
      5.5]), dirty surgery (OR = 3.2 [1.0-9.9]), length of the intervention (OR [every
      hour] = 1.5 [1.2-2.0]), diabetes mellitus or chronic obstructive pulmonary
      disease (OR = 2.6 [1.2-5.6]) and functional grade according to the New York Heart
      Association (OR = 3.4 [1.5-7.7]). The proportion of deep infection attributable
      to prolonged preoperative stay was 41.8% (4.0-58.2). CONCLUSIONS: The incidence
      of deep surgical infection may be decreased with a reduction, whenever possible,
      of the length of surgical intervention and preoperative stay.

PMID- 7623503
TI  - [Hemorrhagic incidents during prolonged ambulatory treatment with acenocoumarol].
AB  - BACKGROUND: To analyze hemorrhagic complications in a series of outpatients
      treated with acenocoumarol in an anticoagulant specialized unit by a prospective
      observational clinical study. PATIENTS AND METHODS: 1,200 outpatients (682
      women/518 men, mean age 54.6 +/- 15.8 yrs.) treated with acenocoumarol for at
      least 6 weeks, with a total follow-up of 2,795 patients-yr. Prevalence and
      incidence of bleeding was analyzed. The episodes that were potentially life
      threatening, or forced to blood transfusion or hospital patient admittance were
      considered as major bleedings, and the remainder episodes were minor. RESULTS:
      There were 379 minor bleedings in 258 patients (incidence 13.56/100 patients
      yr.), 45 major bleedings (1.61/100 patients-yr.) and 2 lethal bleedings (0.07/100
      patients-yr.). Minor bleedings correlated with more advanced age (57.3 +/- 11.8
      vs. 53.9 +/- 16.7 yrs., p = 0.002), with the first two months in treatment in the
      511 patients who start the treatment during the study (31.09 vs. 13.04/100
      patients-yr., p < 0.001), and with a worse achievement of the desired
      anticoagulation (72.4% vs. 81.6%; p = 0.002). Major bleeding was associated with
      local causes in 48.9%, and with an excessive anticoagulation in 35.6%.
      CONCLUSIONS: Bleeding is relatively frequent during acenocoumarol therapy, mainly
      in patients with worse control, but only in a few of these episodes is severe,
      and is usually associated with local lesions.

PMID- 7623504
TI  - [Economic study of the cost of peripheral blood hematopoietic precursor
      autotransplantation compared with bone marrow transplantation].
AB  - BACKGROUND: Rescue with progenitor cells (blood or bone marrow) following
      intensive chemotherapy is used ever more frequently and the results are
      particularly satisfactory in leukemias and lymphomas. Nonetheless, the real cost
      of this procedure is not known in Spain, thus the aim of this study. METHODS: The
      costs of autologous bone marrow transplantation (ABMT) in 10 patients was
      compared with another group of 10 patients with the same type of tumoral
      pathology in which autologous transplantation of peripheral blood precursors
      (APBP) was used. The period studied included from the first intervention related
      with the transplantation to 30 days post transplantation. RESULTS: The mean total
      price of ABMT (1,998 +/- 372 thousand pesetas) is similar to that of APBP (1,736
      +/- 383). The length of neutropenia was lower in the APBP requiring fewer
      platelet transfusions but these difference did not reflect in significantly fewer
      admissions or in a lesser use of antibiotics. The main expense in both procedures
      was that of pharmacy followed by blood bank expenses in the ABMT and the expenses
      of obtaining hematopoietic precursors in the APBP. The saving achieved with the
      APBP in relation with its faster recovery are countered by the greater cost in
      obtaining the progenitor cells. Some factors (platelet support and days in the
      Intensive Care Unit) are responsible for the excessive increases in the cost of
      these procedures. CONCLUSIONS: Although the transfusion requirements are lesser
      in autologous transplantation of hematopoietic precursors and the speed of
      hematologic recovery is greater than in autologous bone marrow transplantation,
      the cost of both procedures is identical.

PMID- 7623505
TI  - [The bipolar disease].

PMID- 7623506
TI  - [Hepatitis C and hemophilia].

PMID- 7623507
TI  - [General internal medicine under debate: history of a crisis and recovery].

PMID- 7623508
TI  - [Cardiogenic shock in a 75-year-old man].

PMID- 7623509
TI  - [Negative polymerase chain reaction in 2 cases of herpetic encephalitis].

PMID- 7623510
TI  - [Bullous pemphigoid and multiple sclerosis].

PMID- 7623511
TI  - [Guillain-Barre syndrome with anti-HIV seroconversion].

PMID- 7623512
TI  - [Idiopathic lactic acidosis in a patient with AIDS].

PMID- 7623513
TI  - [Rare forms of HIV-1 transmission].

PMID- 7623514
TI  - [CD4+ lymphocytopenia and sarcoidosis].

PMID- 7623515
TI  - [Contribution to the epidemiology of bacterial meningitis].

PMID- 7623516
TI  - The effects of two inositol (1,4,5)-trisphosphate 5-phosphatase inhibitors on
      thyrotropin releasing hormone stimulated inositol (1,4,5)-trisphosphate
      production in GH3 cells.
AB  - The effects of FLA99 and EWP840, two disulfiram analogs which potently inhibit
      Ins(1,4,5)P3 5-phosphatase, upon basal and thyrotropin-releasing hormone (TRH)
      stimulated inositol (1,4,5)-trisphosphate (Ins(1,4,5)P3) levels were
      investigated. Neither test compound affected the characteristics of the
      [3H]Ins(1,4,5)P3 binding site used in the competitive protein binding assay of
      Ins(1,4,5)P3 levels. In rat GH3 pituitary cell suspensions, TRH (100 nM) produced
      a large and time-dependent increase in Ins(1,4,5)P3 concentration, the maximum
      response being obtained within 5 seconds of stimulation in these cells. Neither
      FLA99 (100, 300 and 1000 microM) nor EWP840 (100 microM) produced obvious effects
      on the Ins(1,4,5)P3 response to TRH stimulation. Higher concentrations of EWP840
      (300 and 1000 microM) abolished the Ins(1,4,5)P3 response to TRH stimulation. The
      lack of effect of the 5-phosphatase inhibition in the cells may indicate that 5
      phosphatase is not the major metabolic pathway of this second messenger in this
      cell line under the assay conditions used.

PMID- 7623517
TI  - Intracellular lucifer yellow leakage from Novikoff cells in the presence of ATP
      or low extracellular Ca: evidence for hemi-gap junction channels.
AB  - Lucifer Yellow was microinjected into Novikoff hepatoma cells and leakage was
      investigated under treatment with ATP (5 mM) and EGTA (5 mM) in the culture
      medium. In control conditions, there was no leakage in single or paired cells,
      except a few cases which showed very slow leakage (defined as slope < 
      0.0007/sec). Slow leakage rate (slope > -0.0008 but < -0.009/sec) and quick
      leakage rate (slope > -0.01) of intracellular dye were not seen. Dye transfer
      between cell pairs after Lucifer Yellow was injected into one cell was divided
      into two groups: quick transfer rates (4 cases, slope = -0.151 +0.0032) and slow
      transfer rates (15 cases, slope = -0.041 +0.0018). Under ATP treatment the
      intracellular dye leakage was observed in single cells (16 of 31 cases) and in
      cell pairs (20 of 57 cases). Extracellular low Ca2+ (EGTA treatment) enhanced the
      dye leakage much more: 30 of 40 cases in single cells and 21 of 36 cases in cell
      pairs. The leakage rates of intracellular dye under these treatments were similar
      to the transfer rates of the dye between cell pairs with quick and slow rates. It
      is suggested that the dye leakage from Novikoff cells under treatment with ATP or
      low [Ca2+]o shares the same mechanism as dye transfer through gap junctions,
      suggesting that the hemichannels in the plasma membrane can be opened under
      certain conditions.

PMID- 7623518
TI  - Enzymatic method for quantitating creatine kinase M and B isoenzyme composition
      in cardiac tissue: consideration for utilization in studies of developing and
      adult rat heart.
AB  - Creatine kinase (CK) is a cardiac enzyme of interest due to its involvement in
      both mitochondrial and contractile protein aspects of heart function. Studies on
      the structure, function, and developmental expression of myofibrillar CK led to
      the identification of specific isoenzymes whose synthesis can be mediated by
      changes in expression at two primary gene loci. Experimental interventions which
      alter gene expression and protein synthesis in other cardiac enzymes have been
      attempted to pinpoint underlying genetic and molecular CK control mechanisms. CK
      isoenzymes can be separated electrophoretically and then quantitated by
      densitometry; however, these methods are time consuming and require specialized
      instruments. Enzyme specific activity can be assessed spectrophotometrically, but
      this method, alone, does not provide isoenzyme quantitation. The present work
      establishes a rapid, simple spectrophotometric enzyme assay procedure based on
      relative thermal lability to quantitate tissue CK isoenzyme composition.
      Applicability to cardiac tissue having (a) heterogeneous muscle/nonmuscle cells
      and (b) heterogeneous subcellular fractions within a given cell population was
      evaluated. Results show that cardiac tissue from newborn, weanling, and adult
      rats undergoes dramatic and progressive augmentation of overall CK enzyme
      activity that may be mediated, at least in part, by altered CK gene expression.
      However, based on adult rat heart analyses, it is also apparent that cell makeup
      and fractional composition of subcellular constituents require consideration. The
      described activation energy method is simple, rapid, and reliable for initial
      screening for potential changes in CK isoenzyme expression which can then be
      verified by more detailed, albeit more complex, methodology involving mRNA and/or
      cDNA analyses.

PMID- 7623519
TI  - Different actions of some relaxant agents acting via the cAMP system in rat
      uterus.
AB  - The influence of propranolol, isoprenaline, papaverine and caffeine on basal tone
      and contractile responses to spasmogens (oxytocin, KCl) was investigated in the
      presence and the absence of external calcium in estrogen-treated rat uterus.
      Isoprenaline, papaverine and caffeine relaxed precontracted uterus and caffeine
      also decreased the basal tone of uterine muscle in calcium-containing or calcium
      free solution. Propranolol had a dual activity in calcium-free medium: lower
      concentrations contracted the sustained contraction elicited by oxytocin, whereas
      the highest concentration partially relaxed it. In calcium-containing solution
      the highest dose of propranolol partially inhibited KCl-induced contractions.

PMID- 7623520
TI  - Atrial natriuretic peptide II and III stimulation of Na+/H+ exchange in human
      erythrocytes.
AB  - In the present study we investigated in human red blood cells, the effect of the
      atrial natriuretic polypeptide fragments ANPI, ANPII, ANPII, alpha-ANP and des
      Ser5,Ser6-ANPIII, in a combination range of 1 pM to 100 nM, upon the Na+/H+
      exchange. We have shown that ANPII and ANPIII stimulate the erythrocyte Na+/H+
      exchange while alpha-ANP, ANPI and des-Ser5,Ser6-ANPIII have no effect. In the
      present study, we also tested the hypothesis that ANPIII stimulation of
      erythrocyte Na+/H+ exchange occurs via an increase in cGMP levels. When the
      quinolinedione, 6-anilo-5,8-quinolinedione (LY83583) (10 microM), was used to
      block formation of cGMP in human red blood cells, it was found that basal and
      ANPIII stimulated Na+/H+ exchange were inhibited. The cGMP analogs, dibutyryl
      cGMP and 8-Br-cGMP, also increase the erythrocyte Na+/H+ exchange. The 8-Br-cGMP
      stimulated Na+/H+ exchange was not affected by 2-0-propoxyphenyl-8-azapurine-6
      one (MB22948), an inhibitor of cGMP phosphodiesterase MB22948 alone also
      increased levels of Na+/H+ exchange. The ANPIII stimulated Na+/H+ exchange was
      also accompanied by an elevation of the intracellular cGMP level. Since
      inhibition of cGMp formation blocks ANP111-stimulated Na+/H+ exchange and
      inhibition of cGMP breakdown enhances it, we conclude that ANP111 stimulation of
      Na+/H+ exchange in human red blood cells is mediated via increases in
      intracellular cGMP levels.

PMID- 7623521
TI  - Effect of dotarizine on electroconvulsive shock or pentylenetetrazol-induced
      amnesia and on seizure reactivity in rats.
AB  - Dotarizine (DOT), a compound performing both as calcium antagonist and as 5-HT2
      receptor antagonist, was evaluated for its ability to protect against
      electroconvulsive shock (ECS)- and pentylenetetrazol (PTZ)-induced performance
      deficit in a passive avoidance "step-down" task in rats. Its effect on electric
      and PTZ seizure models was also studied. DOT administered orally at a dose of 50
      mg/kg for 5 days before learning had no significant effect on retention tests
      given 3 h, 24 h and 7 days after the training session. It should be noted,
      however, that DOT completely prevented ECS- and PTZ-induced amnesia in passive
      avoidance situation. DOT had a pronounced protective effect against electric
      seizures but did not affect PTZ seizures. The present results provide additional
      evidence for the role of serotonergic neurotransmitter system and calcium
      homeostasis for memory and seizure reactivity and may be important in the
      development of effective treatment strategies for memory dysfunction.

PMID- 7623522
TI  - Comparison of bioimpedance and Doppler ultrasound cardiac output in CAPD
      patients.
AB  - The reproducibility and reliability of cardiac output (CO) measurement by
      transthoracic electrical bioimpedance (TEB) and dual beam Doppler ultrasound
      methods were compared in 9 uremic patients during treatment with continuous
      ambulatory peritoneal dialysis (CAPD). CO was measured simultaneously by each
      method during supine rest and 70 degree passive head-up tilt on two separate
      days. The effect on CO after the infusion of dialysate was also studied on day 1.
      CO, stroke volume (SV) and heart rate (HR) measurements were reproducible by each
      method. The median day to day differences (95% confidence intervals) in CO and SV
      were 0.6 (-0.3, 1.8) l/min and 10 (-1.5, 24.5) ml for TEB and 0.7 (-0.5, 2.2)
      l/min and 13 (-1.0, 30.5) ml for Doppler at supine rest; 0.4 (-0.2, 0.9) l/min
      and 11 (-0.5, 19.0) ml for TEB and 0.5 (-0.3, 1.2) l/min and 8 (-5.0, 16.0) ml
      for Doppler during tilt (p > 0.05 in each case). Data were unobtainable by TEB at
      five time points while none were lost by Doppler. This is due to incorrect HR or
      poor quality signals detected by TEB. CO and SV measured by Doppler were higher
      than that by TEB during supine rest (p < or = 0.01) but not during passive tilt.
      As a result, there was significant change (p < or = 0.01) in CO and SV from
      supine to tilt measured by Doppler but not by TEB. Neither TEB nor Doppler
      detected significant change (p > 0.05) in CO or SV after the infusion of
      dialysate, in either the supine or tilt positions.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7623523
TI  - Pharmacokinetics of acetylsalicylic acid and its metabolites at low doses: a
      compartmental modeling.
AB  - The pharmacokinetics of acetylsalicylic acid (ASA) and its metabolites salicylic
      acid (SA) and salicyluric acid (SUA) were studied in 12 healthy young volunteers
      after oral administration of low (30 and 100 mg) and moderate (400 mg) doses.
      Plasma and urine were assayed for the above drugs by high-performance liquid
      chromatographic method. Individual pharmacokinetic parameters were estimated by
      compartmental modeling (ASA and SA) and by model-independent methods (SUA). ASA
      parameter values estimated in this study were in agreement with those reported by
      other authors after administration of higher doses, which confirms the linearity
      of ASA pharmacokinetics in a broad dose range. On the contrary, both metabolic
      and renal elimination routes for SA were found to be saturable. The relative
      changes in SA renal clearance with the dose were more pronounced than those in
      metabolic clearance. Particularly, there was no statistically significant
      difference in SA metabolic clearance between 30 and 100 mg doses, indicating the
      linear kinetics in this dose range. Further increase in the dose resulted in
      significant decrease in SA metabolic clearance. At the same time, both SA
      excretion rate constant and fraction excreted significantly diminished across the
      entire dose range studied. The dependence of SUA renal clearance upon the dose
      was shown to be complex, reflecting possible saturability of its excretion.

PMID- 7623524
TI  - Anti-drug counterblast in mental health.

PMID- 7623525
TI  - Another coronary reperfusion regimen.

PMID- 7623526
TI  - Hair-cell regeneration: cure for deafness?

PMID- 7623527
TI  - HIV test results, partner notification, and personal conduct.

PMID- 7623528
TI  - On putting life first.

PMID- 7623529
TI  - Foreign aid and TB control policy in Nepal.

PMID- 7623530
TI  - Randomised, double-blind comparison of reteplase double-bolus administration with
      streptokinase in acute myocardial infarction (INJECT): trial to investigate
      equivalence. International Joint Efficacy Comparison of Thrombolytics.
AB  - Streptokinase and alteplase are established therapies in acute myocardial
      infarction. Reteplase is a new thrombolytic agent that can be given as a double
      bolus. This trial was designed to determine whether the effect of reteplase on
      survival was at least equivalent (within 1% of fatality rate) to that of a
      standard streptokinase regimen. Patients from 208 centres in nine countries (n =
      6010) with symptoms and electrocardiographic criteria consistent with acute
      myocardial infarction were randomised to receive double-blind either
      streptokinase 1.5 MU intravenously over 60 min or reteplase two boluses of 10 MU
      given 30 min apart. Treatment could be started up to 12 h from onset of symptoms.
      All patients received intravenous heparin for at least 24 h. The primary endpoint
      was 35-day outcome. There were 270 deaths (9.02%) in the reteplase and 285 deaths
      (9.53%) in the streptokinase group, a non-significant difference (95% CI -1.98%
      to 0.96%). Among patients who received treatment (98.8%) there were 263 deaths
      (8.90%) in the reteplase compared with 279 deaths (9.43%) in the streptokinase
      group (a difference of -0.53%). Because the upper limit of the 90% CI for this
      difference is 0.71%, this result shows that reteplase is at least as effective as
      streptokinase. In-hospital stroke rates were 1.23% for reteplase and 1.00% for
      streptokinase. Bleeding events were similar in the two treatment groups (0.7%
      reteplase, 1.0% streptokinase). The incidence of recurrent myocardial infarction
      was similar, but there were significantly fewer cases of atrial fibrillation,
      asystole, cardiac shock, heart failure, and hypotension in the reteplase group.
      We conclude that reteplase is an effective drug in the treatment of acute
      myocardial infarction. It is clinically safe, its administration is simple, and
      it will be a useful addition to the range of thrombolytic agents available.

PMID- 7623531
TI  - Phase II trial of 131I-B1 (anti-CD20) antibody therapy with autologous stem cell
      transplantation for relapsed B cell lymphomas.
AB  - 25 patients with relapsed B-cell lymphomas were evaluated with trace labelled
      doses (2.5 mg/kg, 185-370 MBq [5-10 mCi]) of 131I-labelled anti-CD20 (B1)
      antibody in a phase II trial. 22 patients achieved 131I-B1 biodistributions
      delivering higher doses of radiation to tumour sites than to normal organs and 21
      of these were treated with therapeutic infusions of 131I-B1 (12.765-29.045 GBq)
      followed by autologous haemopoietic stem cell reinfusion. 18 of the 21 treated
      patients had objective responses, including 16 complete remissions. One patient
      died of progressive lymphoma and one died of sepsis. Analysis of our phase I and
      II trials with 131I-labelled B1 reveal a progression-free survival of 62% and an
      overall survival of 93% with a median follow-up of 2 years. 131I-anti-CD20 (B1)
      antibody therapy produces complete responses of long duration in most patients
      with relapsed B-cell lymphomas when given at maximally tolerated doses with
      autologous stem cell rescue.

PMID- 7623532
TI  - Guidelines for management of HIV infection with computer-based patient's record.
AB  - Computers are steadily being incorporated in clinical practice. We conducted a
      nonrandomised, controlled, prospective trial of electronic messages designed to
      enhance adherence to clinical practice guidelines. We studied 126 physicians and
      nurse practitioners who used electronic medical records when caring for 349
      patients with HIV infection in a primary care practice. We analysed the response
      times of clinicians to the situations that triggered alerts and reminders, the
      number of ambulatory visits, and hospitalisation. The median response times to
      303 alerts in the intervention group and 388 alerts in the control group were 11
      and 52 days (p < 0.0001), respectively. The median response time to 432 reminders
      in the intervention group was 114 days and that for 360 reminders in the control
      group was over 500 days (p < 0.0001). There was no effect on visits to the
      primary care practice. There was, however, a significant increase in the rate of
      visits outside the primary care practice (p = 0.02), which is explained by the
      increased frequency of visits to ophthalmologists. There were no differences in
      admission rates (p = 0.47), in admissions for pneumocystosis (p = 0.09), in
      visits to the emergency ward (p = 0.24), or in survival (p = 0.19). We conclude
      that the electronic medical record was effective in helping clinicians adhere to
      practice guidelines.

PMID- 7623533
TI  - Variation in outcome after acute upper gastrointestinal haemorrhage. The National
      Audit of Acute Upper Gastrointestinal Haemorrhage.
AB  - Hospital mortality after acute upper gastrointestinal haemorrhage varies widely.
      In a population-based, multi-centre, prospective survey of the management and
      outcome of unselected cases of acute upper gastrointestinal haemorrhage, we have
      assessed the effect of risk standardisation on this variation. We collected data
      from 74 acute hospitals in four health regions in the UK on patients aged 16
      years and over who presented with acute upper gastrointestinal haemorrhage during
      4 months in 1993 (3981 cases) and 3 months in 1994 (1584 cases). The overall
      mortality was 14.3% (798/5565). Crude mortality in individual hospitals ranged
      from 0% to 29%, and differed significantly from the overall rate in eight. Risk
      standardised mortality ratios were calculated with a risk score derived from well
      established risk factors. Only two hospitals had standardised mortality ratios
      significantly different from the reference value. When hospitals were ranked in
      order of increasing mortality, risk standardisation for age, shock, and
      comorbidity resulted in 21 of the 74 hospitals changing ranks by ten or more
      places. After further standardisation for diagnosis, endoscopic stigmata of
      recent haemorrhage, and rebleeding, 32 hospitals moved ten or more places from
      their original rank; one hospital moved 45 places. Risk standardisation to
      correct for variation in case mix results in apparently significant differences
      in mortality rates becoming non-significant. The current state of routine data
      collection does not allow for anything but the most basic case-mix adjustment to
      be made. Simple league tables of crude mortality are misleading in this disorder
      and cannot be regarded as a reflection of the quality of health care.

PMID- 7623534
TI  - Percutaneous computed-tomography-guided thermocoagulation for osteoid osteomas.
AB  - Current treatment for osteoid osteomas is usually surgical excision of the nidus.
      We treated 18 patients with osteoid osteoma by percutaneous thermocoagulation of
      the nidus under computed-tomography guidance. The procedure was technically
      successful in all cases and there were no complications. Patients were discharged
      on the following morning and resumed normal activities immediately. All patients
      but one remained pain free during follow-up (range 3-15 months). A second
      thermocoagulation treatment relieved the recurrent symptoms in this patient.
      Percutaneous thermocoagulation appears to be effective for osteoid osteomas, and
      is a minimally invasive alternative to surgical resection.

PMID- 7623535
TI  - HIV-associated diarrhoea and wasting.

PMID- 7623536
TI  - Attitudes of Japanese and Japanese-American physicians towards life-sustaining
      treatment.
AB  - Doctors in different countries have different approaches to bioethical problems.
      We studied how attitudes to life-sustaining treatment for terminally ill patients
      differ in Japan and the USA by administering a questionnaire to Japanese (136)
      and Japanese-American (77) physicians. In a series of clinical scenarios the
      questionnaire asked what life-sustaining interventions the doctors would
      recommend to a patient with metastatic gastric cancer. Most Japanese physicians
      would recommend blood transfusions for gastrointestinal bleeding (74%), total
      parenteral nutrition for malnutrition (67%), and vasopressors for life
      threatening hypotension (61%) when the patient did not know of his diagnosis and
      outlook. Significantly fewer Japanese physicians would want these interventions
      for themselves: 29% would want transfusion, 36% would want total parenteral
      nutrition, and 25% would want vasopressors. 36% of Japanese physicians would
      override the explicit request of a competent moribund cancer patient to withdraw
      all life-support. By contrast, among Japanese-American physicians only 42% would
      recommend blood transfusions, 33% total parenteral nutrition, and 34%
      vasopressors to a terminally ill cancer patient who did not know of his diagnosis
      or outlook. Cross-cultural studies in medical ethics can help physicians and the
      public in different countries to take a fresh look at accepted practices and the
      ethical reasons behind them.

PMID- 7623537
TI  - Do refugees belong in camps? Experiences from Goma and Guinea.

PMID- 7623538
TI  - Child protection at home and abroad.

PMID- 7623540
TI  - Italy's reproductive risks are lowest in world.

PMID- 7623539
TI  - No cheers for baboon to AIDS patient xenotransplant.

PMID- 7623541
TI  - Hepatic focal nodular hyperplasia in infant antenatally exposed to steroids.

PMID- 7623542
TI  - Docetaxel-induced alopecia can be prevented.

PMID- 7623543
TI  - Hepatitis C infection from anti-D immunoglobulin.

PMID- 7623544
TI  - Clinical assessment of deep vein thrombosis.

PMID- 7623545
TI  - Multiplex PCR analysis of RhD gene.

PMID- 7623547
TI  - Treatment of cutaneous T-cell lymphoma by retinoids and calcitriol.

PMID- 7623546
TI  - Treatment of cutaneous T-cell lymphoma by retinoids and calcitriol.

PMID- 7623548
TI  - Can cytotoxic drugs cure subacute sclerosing panencephalitis?

PMID- 7623549
TI  - Fraud in medical science.

PMID- 7623550
TI  - Medical libraries and leap of faith.

PMID- 7623551
TI  - Failure of treatment centres to prevent cholera deaths in Goma.

PMID- 7623552
TI  - Ultrasound and abdominal tuberculosis.

PMID- 7623553
TI  - Tuberculosis: history of directly observed therapy.

PMID- 7623554
TI  - Preliminary experience with predictive testing for insulin-dependent diabetes
      mellitus.

PMID- 7623556
TI  - Nasal airway versus oral route for infant resuscitation.

PMID- 7623557
TI  - Transmural myocardial ischaemia during dobutamine stress echocardiography.

PMID- 7623555
TI  - Long-term sequelae of Helicobacter pylori gastritis.

PMID- 7623558
TI  - Long-term adverse effects of scuba diving.

PMID- 7623559
TI  - Long-term adverse effects of scuba diving.

PMID- 7623560
TI  - Benefit of docosahexaenoic acid supplements to dark adaptation in dyslexics.

PMID- 7623561
TI  - Long-term adverse effects of scuba diving.

PMID- 7623562
TI  - Bird attacks on milk bottles and campylobacter infection.

PMID- 7623563
TI  - Medicine's lottery losers: it could be you.

PMID- 7623565
TI  - Mycophenolate mofetil for transplantation: new drug, old problems?

PMID- 7623564
TI  - S182: from worm sperm to Alzheimer's disease.

PMID- 7623566
TI  - Rheumatic carditis.

PMID- 7623567
TI  - Genes, blood pressure, and African heritage.

PMID- 7623568
TI  - Risks of orofacial clefts in children born to women using multivitamins
      containing folic acid periconceptionally.
AB  - Women are advised to take folic acid before they conceive as a precaution against
      neural-tube defects. However, the use of folic acid in preventing orofacial
      clefts is unknown. We investigated whether a woman's periconceptional use of
      multivitamins containing folic acid was associated with a reduced risk of
      orofacial clefts. We derived data from a population-based case-control study of
      fetuses and liveborn infants with orofacial anomalies among a 1987-89 cohort of
      births in California. We interviewed 731 (84.7%) of eligible mothers with
      orofacial cleft case infants and 734 (78.2%) mothers with non-malformed control
      infants. We found a reduced risk of orofacial clefts if the mother had used
      multivitamins containing folic acid during the period from one month before
      through two months after conception. The odds ratios ranged from 0.50-0.73
      depending on cleft phenotype. Controlling for the potential influence of other
      variables did not substantially alter the results. Maternal daily consumption of
      cereal containing folic acid was also associated with a reduced risk of orofacial
      clefts. Women who used multivitamins containing folic acid periconceptionally had
      a 25-50% reduction in risk for offspring with orofacial clefts compared to women
      who did not use such vitamins. However, this association may not be attributable
      to folic acid specifically, but may be a consequence of other multivitamin
      supplement components, or behaviours, that are highly correlated with the use of
      multivitamins containing folic acid.

PMID- 7623569
TI  - Insulin resistance: interactions between obesity and a common variant of insulin
      receptor substrate-1.
AB  - We previously discovered two aminoacid polymorphisms in codons 513 and 972 of the
      protein insulin receptor substrate-1 (IRS-1), which is important in cellular
      insulin action. We have investigated whether these polymorphisms are associated
      with changes in insulin sensitivity in a random sample of young healthy adults.
      Insulin sensitivity and secretion were measured during a combined intravenous
      glucose and tolbutamide tolerance test in 380 unrelated white subjects aged 18
      32. IRS-1 polymorphisms were examined by single-strand conformation polymorphism
      and verified by restriction-enzyme digestion. No homozygous carrier of the codon
      513 variant was identified, but one non-obese man had the codon-972 mutation on
      both alleles. He had low fasting-serum insulin and C-peptide concentrations and
      low insulin sensitivity and glucose effectiveness. During a 24 h dexamethasone
      test, he developed transient diabetes. In their heterozygous forms the codon-513
      and codon-972 variants of IRS-1 were found in 3% and 9% of the subjects. Non
      obese carriers of either polymorphism had similar insulin sensitivity and
      pancreatic beta-cell function to non-obese wild-type subjects (no known variants
      of IRS-1). Analysis of variance showed, however, a significant interaction
      between obesity (body-mass index > or = 25 kg/m2) and the heterozygous form of
      the codon-972 variant (p < 0.003); obese polymorphism carriers had lower insulin
      sensitivity than obese non-carriers (mean 6.0 [SD 3.3] vs 12.3 [9.5] x 10(-5) L
      min-1 pmol-1). The obese carriers of the codon-972 variant were also
      characterised by a clustering of metabolic cardiovascular risk factors, with
      raised fasting concentrations of plasma glucose, serum triglyceride, and plasma
      tissue-plasminogen-activator and its fast-acting inhibitor. With adjustment for
      known modulators of insulin sensitivity, multivariate analyses showed that the
      combination of obesity and the codon-972 variant was associated with a 50%
      reduction in insulin sensitivity (p = 0.0008). Our results suggest that the codon
      972 IRS-1 gene variant may interact with obesity in the pathogenesis of common
      insulin-resistant disorders.

PMID- 7623570
TI  - Risk of neoplasia in renal transplant patients.
AB  - Renal allograft recipients are at an increased risk of neoplasia, although the
      extent of the problem has not been established in a typical European transplant
      population. To assess this risk we did a comprehensive, retrospective study of
      918 patients transplanted at one centre over 24 years. The centre (Leeds) serves
      Yorkshire and Humberside, a region in northern England with a population of 3.6
      million. The search, which made use of six sources of information, revealed 70
      patients (7.6%) who had developed a neoplastic lesion, 10 patients having more
      than one type. More than half (42) were cutaneous lesions (mostly squamous cell
      carcinomas). The risk of developing neoplasia in the first 10 years after
      transplantation was calculated to be 14%. By 20 years this had risen to 40%
      compared with a 6% cumulative risk of neoplasia in an age-matched control
      population (p < 0.005). The full extent of this problem in the European
      transplant population has been underestimated and, now that recipients are
      surviving longer, there is a clear need for both lifelong surveillance and closer
      investigation of these patients.

PMID- 7623571
TI  - Inpatient general medicine is evidence based. A-Team, Nuffield Department of
      Clinical Medicine.
AB  - For many years clinicians have had to cope with the accusation that only 10-20%
      of the treatments they provide have any scientific foundation. Their
      interventions, in other words, are seldom "evidence based". Is the profession
      guilty as charged? In April, 1995, a general medical team at a university
      affiliated district hospital in Oxford, UK, studied the treatments given to all
      109 patients managed during that month on whom a diagnosis had been reached.
      Medical sources (including databases) were then searched for randomised
      controlled trial (RCT) evidence that the treatments were effective. The 109
      primary treatments were then classified: 82% were evidence based (ie, there was
      RCT support [53%] or unanimity on the team about the existence of convincing non
      experimental evidence [29%]). This study, which needs to be repeated in other
      clinical settings and for other disciplines, suggests that earlier pessimism over
      the extent to which evidence-based medicine is already practised is misplaced.

PMID- 7623572
TI  - Eosinophilic colitis associated with larvae of the pinworm Enterobius
      vermicularis.
AB  - Various helmintic parasites, most of which are uncommon in economically developed
      countries, can cause abdominal pain and eosinophilic inflammation of the bowel. A
      homosexual man presented with severe abdominal pain and haemorrhagic colitis,
      eosinophilic inflammation of the ileum and colon, and numerous unidentifiable
      larval nematodes in diarrhoeal stool. His symptoms resolved with anthelmintic
      treatment alone. Using comparative morphology and molecular cloning of nematode
      ribosomal RNA genes, we identified the parasites as larvae of the pinworm
      Enterobius vermicularis, which are rarely observed or associated with disease.
      Occult enterobiasis is widely prevalent and may be a cause of unexplained
      eosinophilic enterocolitis.

PMID- 7623573
TI  - Hyperosmolar coma due to lithium-induced diabetes insipidus.

PMID- 7623574
TI  - In-hospital mortality after out-of-hospital cardiac arrest.
AB  - In-hospital management of out-of-hospital cardiac arrest is complicated by
      uncertainty about prognosis and the need to identify markers of adverse outcome
      in individuals surviving initial resuscitation. We sought to identify factors
      that predict in-hospital death among patients who initially survive out-of
      hospital cardiac arrest. We investigated 346 consecutive cases of out-of-hospital
      cardiac arrest received by a single centre in Edinburgh, UK (270 cases examined
      retrospectively, 76 prospectively). Of the retrospective cohort, 246 cases were
      thought to be of cardiac origin. There were associations between in-hospital
      mortality and pre-arrest variables, resuscitation variables, and factors measured
      during admission. Crew-witnessed arrests were associated with low mortality;
      arrest rhythm (p < 0.001), resuscitation by a health professional (p < 0.05),
      conscious level on admission (p < 0.001), and requirement for ventilation (p <
      0.05) independently predicted in-hospital mortality. A weighted prognostic
      scoring system based on three of these variables accurately predicted the
      likelihood of in-hospital death in the prospective test group. Further assessment
      of conscious level during admission with the Glasgow coma score predicted
      mortality rates in the study population, but coma did not predict a hopeless
      prognosis in individual cases unless it persisted for 72 h or more. Accurate
      prognostic assessment of out-of-hospital cardiac arrest survivors can be made
      from information available on admission. Of factors that independently predicted
      outcome, the skill of the resuscitator is most readily modified. This suggests
      that public training in resuscitation may reduce mortality rates.

PMID- 7623575
TI  - Integration of primary health care concepts in a children's hospital with limited
      resources.
AB  - After nearly 30 years of war, health services in Vietnam were devastated.
      Pediatric Hospital Number 1 (PH1) in Ho Chi Minh City was severely overloaded,
      mortality rates for readily treatable diseases were high, and staff competence
      and motivation were low. In 1988, PH1 introduced primary health care (PHC)
      concepts into the policy of the hospital. The approach included identification of
      priority diseases that are most easily treatable (diarrhoea, acute respiratory
      infections, Dengue haemorrhagic fever, malnutrition, and common paediatric
      emergencies including malaria); establishment of training programmes through
      paediatric priority training units for medical staff of PH1 and health centres
      (district and commune services), and health education for the patients' carers;
      promotion of outpatient treatment to avoid unnecessary admissions; use of
      appropriate technology such as essential drugs and application of WHO guidelines;
      support for health centres; transfer of responsibility for decision-making from
      one central authority to each department; and community participation, by which
      we sought small contributions from families who could afford to pay. Since the
      new approach was implemented, the numbers of admissions have fallen
      substantially. Mortality rates have decreased greatly (diarrhoea by 80%, Dengue
      fever by 64%, and acute respiratory infections by 41%). Support from foreign non
      governmental organisations has enabled training and research to enhance staff
      skill and knowledge and supply of necessary equipment.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7623576
TI  - Implications of variations of "conserved" regions of hepatitis C virus genome.

PMID- 7623577
TI  - Congress goes into recess in state of upheaval.

PMID- 7623578
TI  - Hitch in implementing Russia's HIV-prevention law.

PMID- 7623579
TI  - Immune response to intracellular pathogens.

PMID- 7623580
TI  - Screening for breast cancer, time to think--and stop?

PMID- 7623581
TI  - Screening for breast cancer, time to think--and stop?

PMID- 7623582
TI  - Screening for breast cancer, time to think--and stop?

PMID- 7623583
TI  - Screening for breast cancer, time to think--and stop? National Evaluation Team
      for Breast Cancer Screening (NETB)

PMID- 7623584
TI  - Missense mutation of S182 gene in Italian families with early-onset Alzheimer's
      disease.

PMID- 7623585
TI  - Missense mutation of S182 gene in Japanese familial Alzheimer's disease.

PMID- 7623586
TI  - Dementia.

PMID- 7623587
TI  - Fatal cardiac tamponade through congenital sternal foramen.

PMID- 7623588
TI  - Is tuberculosis in domestic cats hazardous to human beings?

PMID- 7623589
TI  - Vincristine toxicity in five children with acute lymphoblastic leukaemia.

PMID- 7623590
TI  - Quality of life.

PMID- 7623591
TI  - Quality of life.

PMID- 7623592
TI  - Quality of life.

PMID- 7623593
TI  - Quality of life.

PMID- 7623594
TI  - Can overall results of clinical trials be applied to all patients?

PMID- 7623595
TI  - B12/folate assays and macrocytic anaemia.

PMID- 7623596
TI  - Fatal complication of desmopressin.

PMID- 7623597
TI  - Origin of GB-hepatitis viruses.

PMID- 7623598
TI  - Pathognomonic pulse oximetry paradox.

PMID- 7623600
TI  - Viral illness and chronic fatigue (syndrome).

PMID- 7623599
TI  - Role of Helicobacter pylori eradication in high-grade MALT lymphoma.

PMID- 7623601
TI  - Coagulation disorders in bushmaster envenomation.

PMID- 7623602
TI  - Pharmacotherapy of schizophrenia.

PMID- 7623603
TI  - Transmission of HIV in dialysis centres.

PMID- 7623604
TI  - Diagnosis of HIV-1 group O infection by polymerase chain reaction.

PMID- 7623605
TI  - Seizure associated with zidovudine.

PMID- 7623606
TI  - Successful medical treatment of obesity in 10th century Spain.

PMID- 7623607
TI  - Changes in [3H]flunitrazepam binding in the brain of rats made tolerant to and
      dependent upon pentobarbital.
AB  - Changes in benzodiazepine binding sites labeled by [3H]flunitrazepan (FNZ) in
      twenty discrete brain regions of rats made tolerant to and dependent upon
      pentobarbital were examined. Animals were rendered tolerant by
      intracerebroventricular (i.c.v.) infusion with pentobarbital (300 micrograms/ 10
      microliters/ hr for six days) through pre-implanted cannulae connected to osmotic
      mini-pumps. The pentobarbital dependence was assessed 24 hr after abrupt
      withdrawal from pentobarbital. In the tolerant rats, a significant increase in
      [3H]FNZ binding sites was found in layer IV of frontal cortex and the molecular
      layer of olfactory bulb. [3H]FNZ binding sites in the pentobarbital dependent
      rats were significantly increased in layers I-III and V-VI of frontal cortex,
      caudate-putamen, olfactory tubercle, globus pallidus and ventral pallidum, in
      addition to those observed in the tolerant group. There was, however, no
      significant difference in the hippocampus and several regions in the hindbrain in
      either pentobarbital-treated group. Taken together with characteristics of
      subtypes of benzodiazepine receptors and changes in GABA-benzodiazepine receptor
      complexes elucidated in our previous studies, these findings suggest that both
      types of benzodiazepine receptors are involved in the development of
      pentobarbital intoxication mediated by GABAA receptors.

PMID- 7623608
TI  - Restoration of myo-inositol uptake by eicosapentaenoic acid in human skin
      fibroblasts cultured in high-glucose medium.
AB  - The effects of elevated glucose and eicosapentaenoic acid (EPA, C20:5 omega 3) on
      myo-inositol uptake in human skin fibroblasts (HSF) were evaluated. Myo-inositol
      incorporation into HSF was dependent on an active transport system via Na(+)-K+
      ATPase activity based on the results with Na+ deprivation and ouabain (5 mM).
      Although glucose (27.5, 55 mM) inhibited 2-[3H] myo-inositol uptake, the addition
      of EPA (3 x 10(-4) M) prevented glucose-mediated inhibition. Since EPA decreased
      glucose-mediated inhibition of myo-inositol uptake, this agent might ameliorate
      some of the devastating functions associated with diabetes.

PMID- 7623609
TI  - Prozac (fluoxetine, Lilly 110140), the first selective serotonin uptake inhibitor
      and an antidepressant drug: twenty years since its first publication.
AB  - In this review, we describe the evolutionary process involved in the discovery of
      the selective 5-HT uptake inhibitor, fluoxetine, and summarize some of the large
      body of scientific research performed on fluoxetine in the 20 years since the
      first publication. The historical background of the proposed involvement of 5-HT
      in psychiatric disorders and the activity of tricyclic antidepressants in
      depression is reviewed. The effects of fluoxetine in various in vitro assays and
      in animal studies including receptor down-regulation, neurochemical and
      behavioral models are summarized. In addition, the clinical effectiveness of
      fluoxetine in depression and obsessive compulsive disorders and its potential use
      in other disorders are examined.

PMID- 7623610
TI  - A novel bacteristatic action of bovine and porcine serum that is reversed by
      norepinephrine.
AB  - A previously unreported anti-bacterial activity against Escherichia coli has been
      found in porcine and bovine sera, but not in human or chicken sera. The activity
      is not affected by heat inactivation of the complement system, and is
      bacteriostatic rather than bactericidal. Growth inhibition is reversible by
      addition of norepinephrine.

PMID- 7623611
TI  - Gangliosides raise the intracellular Ca2+ level in different cell types.
AB  - Total gangliosides from bovine brain at micromolar concentration induce
      intracellular Ca2+ increments in a temperature, time and dose dependent manner
      when assayed with suspensions of rat macrophages, rat and chicken neurons, human
      erythrocytes and liposomes, loaded with the fluorescent Ca2+ indicator FURA 2.
      The effect was independent on the endogenous ganglioside composition of the cells
      and in the case of neurons it was also independent on the differentiation state.
      Gangliosides do not induce the release of Ca2+ from inner stores. These findings
      indicate that the reported inhibition of arachidonic acid release (Bressler, J.,
      et al., (1994) Life Sci., 54, 49-60) and anti-inflammatory properties of
      gangliosides (Correa, S.G. et al., (1991) Eur. J. Pharmacol. 199, 93-98) are not
      due to impairments of Ca2+ flux. The results also suggest the possibility that
      the well-known neurotrophic effect produced by gangliosides on undifferentiated
      neurons in culture may be due to subtoxic cytosolic Ca2+ increments.

PMID- 7623612
TI  - Adrenomedullin increases cyclic AMP more potently than CGRP and amylin in rat
      renal tubular basolateral membranes.
AB  - In rat renal tubular basolateral membranes, the potency to increase cAMP of
      adrenomedullin (AM), a novel vasorelaxant peptide originally isolated from human
      pheochromocytoma, was compared with those of calcitonin gene-related peptide
      (CGRP) and amylin. Although all three peptides raised cAMP in a time- and
      concentration-dependent manner with a 4-fold increase at 10(-6)-10(-5) M, the
      EC50 value (10(-9) M) of AM was 100-fold smaller than those of CGRP and amylin.
      CGRP[8-37], an antagonist for CGRP receptors, attenuated cAMP elevation induced
      by these peptides with the essentially similar concentration-inhibition curves.
      These results suggest that the receptors for AM, CGRP and amylin share a common
      structural homology, and that the receptors sensitive to AM are preferentially
      expressed in renal tubular basolateral membranes.

PMID- 7623613
TI  - Putative mechanism for guinea pig ileum contraction by N-formyl peptides. A
      comparative study of N-formyl and N-acetyl peptides with the N-terminal sequence
      of the calpain small subunit.
AB  - N-formyl and N-acetyl peptides with the N-terminal sequence of the calpain small
      subunit were prepared and their spasmogenic activity was examined using guinea
      pig ileum preparations. Sections of ileum were found to contract in the presence
      of all N-formyl peptides used (tri- to nonapeptides and tridecapeptide) but
      failed to contract with N-acetyl peptides, although both N-formyl and N-acetyl
      peptides have chemotactic activity, indicating that spasmogenic activity and
      chemotactic activity involve different mechanisms. A formyl peptide antagonist,
      Boc-Phe-Leu-Phe-Leu-Phe, suppressed contraction by formyl peptides whereas a
      histamine antagonist, diphenhydramine, suppressed contraction by formyl peptides
      as well as by histamine. In addition, formyl peptide-induced contractions were
      noted after an approximately 20-sec time lag, and their profiles were bell-shaped
      and roughly symmetrical. On the other hand, histamine- and acetylcholine-induced
      contractions exhibited a much shorter time lag. These data led us to conclude
      that contraction induced by formyl peptides may not occur as a direct response
      but may be due to the histamine released from mast cells present in the tissues
      of the small intestine.

PMID- 7623614
TI  - Effects of acute and chronic estrogenic treatment on vasomotor responses of
      aortic rings from ovariectomized rats.
AB  - The effects of either chronic or acute estrogenic treatment on the "in vitro"
      vasomotor responses to phenylephrine (10(-9)-10(-5) M) and to carbachol (10(-9)
      10(-5) M) of aortic rings excised from ovariectomized rats were analyzed. Chronic
      estrogenic treatment consisted in a single subcutaneous dose of 1 mumol estradiol
      17-stearate. Effects of acute estrogenic treatment were evaluated by recording
      the responses of aortic rings excised from untreated ovariectomized rats both
      before and after the addition of 17 beta-estradiol to the superfusing solutions.
      In order to identify the endothelium-dependent responses each experiment was
      performed simultaneously on pairs of rings from the same aorta, one with and the
      other without functional endothelium. The contractile responses to phenylephrine
      of endothelium-intact vessels were attenuated by chronic estrogenic treatment;
      this attenuation was further increased by preincubation of the vessels with
      indomethacin and was reverted by N omega-nitro-L-arginine methyl ester. Either
      chronic or acute estrogenic treatment enhanced the carbachol-induced endothelium
      dependent relaxation of phenylephrine-precontracted rings. The results may be
      explained by assuming that estrogens increase the basal release of both nitric
      oxide and a cyclooxygenase-dependent vasoconstricting prostanoid as well as the
      receptor-mediated release of nitric oxide from the endothelium of the rat aorta.

PMID- 7623615
TI  - Effect of interleukin-1 beta, tumour necrosis factor-alpha and interleukin-6 on
      the control of thyrotropin secretion.
AB  - Since serum concentrations of tumour necrosis factor-alpha (TNF-alpha),
      interleukin-1 beta (IL-1 beta), and interleukin-6 (IL-6) are elevated in
      infectious and inflammatory illnesses, we examined their potential role in
      contributing to the low TSH concentrations associated with such conditions, both
      at the level of the pituitary and the hypothalamus. 20 hours exposure to
      recombinant murine TNF-alpha (10(-11) to 10(-10) mol/l) enhanced the basal and
      the TRH-stimulated release of TSH by cultured rat anterior pituitary cells, but 4
      hours exposure increased only basal TSH secretion. Recombinant human (rh) IL-1
      beta, at a dose of 10(-11) mol/l only, produced a very small increase in basal
      TSH secretion after 4h, but not 20h, exposure. TRH-stimulated TSH secretion was
      not affected by IL-1 beta in concentrations up to 10(-10) mol/l, at either
      exposure time. Rh IL-6 (10(-12) to 10(-9) mol/l), had no effect on basal or TRH
      stimulated TSH secretion at either exposure time. TNF-alpha, IL-1 beta, and IL-6
      all failed to modify the inhibitory response to triiodothyronine (T3) and
      thyroxine (T4) on TSH secretion, under basal or TRH-stimulated conditions.
      Indirect effects of the cytokines on the stimulation or inhibition of TSH
      secretion, via TRH or SRIF respectively, were tested in isolated rat hypothalamic
      slices. 30 min exposure to TNF-alpha, IL-1 beta, or IL-6 had no effect on the
      basal release of SRIF. However, IL-1 beta, from 2.5 x 10(-12) to 10(-10) mol/l,
      produced a dose-dependent enhancement of the SRIF released by 5 x 10(-2) mol/l
      extracellular K+. The effect appeared to be mediated via IL-1 receptors, and to
      involve prostanoid formation, since it was inhibited by IL-1 receptor antagonist
      protein, 10(-7) mol/l, and indomethacin, 2.8 x 10(-5) mol/l, respectively.
      Neither basal nor K(+)-stimulated TRH release was influenced by TNF-alpha, IL-1
      beta, or IL-6. The results indicate that direct effects of these cytokines on the
      pituitary do not contribute to reduced circulating TSH concentrations during
      inflammation and infection, but that enhanced hypothalamic release of SRIF, in
      response to elevated IL-1 beta, could contribute to such a decrease in TSH. None
      of the cytokines tested decreased hypothalamic TRH release in vitro. However,
      further in vivo experiments would be required to determine whether a longer
      exposure to these agents could reduce TRH release either directly, or indirectly
      via inputs from outside the hypothalamus.

PMID- 7623616
TI  - Safety and tolerability of CI-979 in patients with Alzheimer's disease.
AB  - CI-979 ((E)-1,2,5,6-tetrahydro-1-methyl-3-pyridinecarboxaldehyde, O-methyloxime
      monohydrochloride), a novel muscarinic agonist, is being investigated as a
      potential treatment for Alzheimer's disease (AD). The objective of the present
      study was to determine the safety and tolerance of multiple, rising, oral doses
      of CI-979 in patients with AD. Ten male patients aged 59 to 74 years (mean 65
      years) who met NINCDS criteria for AD were randomized to receive either CI-979
      (eight patients) or placebo (two patients) according to a double-blind, parallel
      group, rising-dose design. Doses were 0.5-mg q6h, 1-mg q12h, 1-mg q6h, 2-mg q12h,
      2-mg q6h, 2.5-mg q6h, and 3-mg q6h. All doses were to be administered
      sequentially for 3 days each with the exception of the 2.5-mg q6h dose, which was
      to be administered for 1.5 days. Five patients receiving CI-979 discontinued
      study medication because of adverse events; two after receiving 2-mg q6h (10
      doses), two after 2.5-mg q6h (5 doses), and one after 3-mg q6h (4 doses). The
      study was terminated following administration of the fourth 3-mg dose due to the
      nature and intensity of adverse events. Cholinergic symptoms including
      diaphoresis, hypersalivation, nausea, diarrhea, hypotension, chills, headache,
      flatulence, and urinary frequency and signs suggestive of parkinsonism
      (cogwheeling, tremor, pillrolling, posturing, and shuffling gait) were dose
      limiting. The frequency and intensity of adverse events increased with increasing
      CI-979 dose. No other clinically significant CI-979-related changes occurred in
      physical examinations, clinical laboratory measurements, electrocardiograms, or
      ophthalmologic examinations. Steady-state trough plasma CI-979 concentrations
      increased in proportion to dose. In summary, CI-979 doses of 1-mg q6h were well
      tolerated by all patients; 2-mg q6h was tolerated by most patients, and 2.5-mg
      and 3-mg doses were poorly tolerated, Dose titration to a maximum of 2-mg q6h
      will therefore be used in initial efficacy trials of CI-979 in patients with AD.

PMID- 7623617
TI  - The role of 5-HT in the expression of morphine withdrawal in mice.
AB  - The effects of methysergide and cyproheptadine on naloxone-precipitated
      withdrawal symptoms were studied in morphine-dependent mice. The effects of these
      drugs were investigated both in normal mice and also mice injected with 6-OHDA
      intracerebrally to destroy the central noradrenergic neurones and examine whether
      5-HT mediated effects are somehow linked to noradrenergic pathways. Methysergide
      given 30 min before naloxone attenuated withdrawal jumping, "wet dog" shakes,
      burrowing and body weight loss but aggravated hypothermia. Similar effects were
      produced by cyproheptadine on withdrawal "wet dog" shakes and hypothermia.
      Jumping was aggravated by low doses and attenuated by higher doses of
      cyproheptadine. Intracerebral injection of 6-OHDA in 5 days old mice pups
      resulted in hyperlocomotion by the end of 30 days before initiation of morphine
      dependence. When they were made morphine-dependent, mice pretreated with 6-OHDA
      developed higher degree of naloxone-induced withdrawal jumping than non-treated
      mice. Methysergide further aggravated jumping but its effect on both "wet dog"
      shakes and burrowing was lost in mice exposed to 6-OHDA. These findings suggest
      that 5-HT receptors are involved in the expression of withdrawal symptoms and the
      functional responsiveness of these receptors is dependent on intact nonadrenergic
      pathways.

PMID- 7623618
TI  - Possible role of endogenous morphine and codeine on growth regulation of lung
      tissue.
AB  - The literature indicates that morphine can inhibit the growth of both small cell
      and non small cell lung cancer cell lines and that nicotine can reverse this
      inhibition. In this report we present data showing that mammalian lung tissue
      contain the opiate alkaloids morphine and codeine and that these alkaloids are
      also to be found in normal lung cell lines. However, analysis of both small cell
      and non small cell lung cancer cells indicate that they do not contain these
      opiate alkaloids endogenously. If morphine exerts an inhibitory effect on
      proliferation of these cells it is interesting that the lung cancer cell lines
      lack the opiate alkaloids endogenously. Our studies also present data indicating
      that the circulating levels of morphine and codeine are elevated in smokers as
      compared to non smokers which we hypothesize to reflect the invocation of a
      compensatory mechanism.

PMID- 7623619
TI  - Vesnarinone inhibits nucleoside and nucleobase transport.
AB  - Vesnarinone is a novel synthetic oral inotropic agent that has been successfully
      used for treatment of patients with congestive heart failure. In addition to its
      cardiotonic activity, the drug has been proposed to have mild cytostatic and anti
      HIV-1 effects. We have observed that vesnarinone profoundly inhibits radiolabeled
      thymidine and uridine incorporation into cells despite its modest inhibitory
      effect on DNA synthesis, RNA synthesis or cell proliferation. Here we demonstrate
      that vesnarinone inhibits both nucleoside and nucleobase transport in mammalian
      cells. This pharmacological action may be involved in some of its multiple
      biological effects.

PMID- 7623620
TI  - Altered brain contents of neuropeptides in spontaneously epileptic rats (SER) and
      tremor rats with absence seizures.
AB  - Immunoreactive- (IR-) somatostatin (SRIF), neuropeptide Y (NPY) and corticotropin
      releasing factor (CRF) contents were investigated in the brain of tremor rats
      with absence-like seizure and spontaneously epileptic rats (SER), which is a
      genetically defined double-mutant (zi/zi, tm/tm) obtained by mating zitter
      homozygote (zi/zi) with tremor heterozygote (tm/+) and shows both absence-like
      seizure and tonic convulsions. Increased levels of IR-NPY and IR-CRF were
      observed in several regions including the amygdala and hippocampus in homozygous
      SER compared to heterozygous SER (zi/zi, tm/+ or +/+). Homozygous tremor rats
      (tm/tm) showed lower levels of IR-NPY and IR-CRF contents mainly in the
      hippocampus and mesolimbic system (entorhinal and pyriform cortex and nucleus
      accumbens) than heterozygous tremor rats. IR-SRIF contents of homozygous SER were
      higher in frontal cortex than heterozygous SER and in amygdala than homozygous
      tremor rats. No change of IR-SRIF between groups was noted in the hippocampus
      among brain structures underlying epileptogenicity. The results suggest that the
      change of neuropeptide levels, most conspicuous in NPY among three peptides
      tested, may be involved in the phenotypical manifestation of seizures in SER and
      tremor rats, and that the development of tonic convulsion and absence seizures
      may be differently associated with the change of brain neuropeptide levels.

PMID- 7623621
TI  - Prolactin secretion in lactating rats following chronic alcohol exposure:
      provocative tests with secretagogues.
AB  - This study was done to examine the mechanism of action of alcohol in inhibiting
      suckling-induced prolactin release in the lactating rat. Alcohol (0.0, 1.0 or 2.0
      g/kg body weight) was administered daily for 8 days from day 5 to 12 of lactation
      via an indwelling atrial catheter, implanted on day 3 of lactation. Following the
      administration of the initial alcohol dose, infusion was continued at rates
      required to maintain the blood alcohol levels (BALs) for four hours every day.
      Prolactin responses to sulpiride and TRH were tested on day 12. Alcohol
      administration for 8 days and maintaining the blood alcohol levels for four hours
      daily did not affect the basal or sulpiride and TRH-stimulated plasma prolactin
      release. Since the prolactin releasing capacity of pituitary lactotropes of the
      lactating rat is not compromised following chronic alcohol exposure, we conclude
      that alcohol does not act at the anterior pituitary level to inhibit the suckling
      induced prolactin release but probably acts by other mechanisms: either via the
      hypothalamic and/or higher central nervous system or by disrupting the neural
      impulse transmission, engendered at the nipples in response to suckling.

PMID- 7623622
TI  - Caffeine increases its own metabolism through cytochrome P4501A induction in
      rats.
AB  - Caffeine is one of the most widely used - and maybe abused - xenobiotic compounds
      in the world. If numerous pharmacological properties of caffeine have been
      reported, the effects of caffeine treatment on the hepatic drug-metabolizing
      enzyme system have been scarcely studied. Pretreatment of rats for 3 days with
      150 mg/kg/day of caffeine dramatically increased P4501A and P4502B dependent
      catalytic activities determined in vitro. Furthermore, N-demethylations and C-8
      oxidation of caffeine were increased by about 2 fold by caffeine treatment.
      Immunoblot analysis demonstrated that the liver contents of P4501A2 and
      P4502B1/2B2, known to be involved in these monooxygenase activities, increased
      also by about 2 fold. Cytochrome P4503A1 and 2E1 were not modified. Taken
      together, there data suggest that caffeine increases its own metabolism through
      P4501A induction.

PMID- 7623623
TI  - Suppression of mouse lymphocyte proliferation in vitro by naturally-occurring
      biflavonoids.
AB  - In a continuing effort to investigate biological activities of flavonoids, nine
      biflavonoids, isolated from three plant sources were evaluated for their
      suppressive effects on mouse lymphocyte proliferation. The biflavonoids tested
      were amentoflavone, bilobetin, ginkgetin, isoginkgetin, sciadopitysin,
      ochnaflavone, 4'-O-methylochnaflavone, cryptomerin B and isocryptomerin. At 10
      uM, several biflavonoids such as ginkgetin, isoginkgetin, ochnaflavone,
      cryptomerin B and isocryptomerin showed the suppressive activity against
      lymphocyte proliferation induced by Con A or LPS. Apigenin (flavone) and
      quercetin (flavonol) were suppressive against Con A-induced lymphocyte
      proliferation, but not against LPS-induced lymphocyte proliferation at the same
      concentration range. Biflavonoids were found to be irreversible inhibitors of
      lymphocyte proliferation. This is the first report describing the suppressive
      effects of naturally-occurring biflavonoids against lymphocyte proliferation.

PMID- 7623624
TI  - Staurosporine induces de novo synthesis of prostaglandin H synthase-2 in rat
      alveolar macrophages.
AB  - This study was initiated to investigate the possible involvement of prostaglandin
      H synthase in the staurosporine-induced prostaglandin production. The time course
      of prostaglandin H synthase activity in macrophages treated with staurosporine
      (20 nM) showed that the maximum activity was reached in 20 h. The stimulatory
      effect of staurosporine on thromboxane B2 production was maximum at 50 nM
      staurosporine and this effect was reversed at higher concentrations.
      Immunoprecipitation of 35S-labeled enzyme using an antibody specific for
      prostaglandin H synthase-2 paralleled the changes in enzyme activity. These
      results indicate that increased de novo synthesis of prostaglandin H synthase-2
      is largely, if not solely, responsible for staurosporine-stimulated prostaglandin
      production in macrophages.

PMID- 7623625
TI  - Effects of defibrotide on leukocytosis in rabbits with diet-induced
      atherosclerosis.
AB  - The antithrombotic drug Defibrotide (DFT) (a polydeoxyribonucleotide with a mean
      MW of 20,000 Daltons) reduces the number of leukocytes and platelets in thrombi.
      Because leukocytes and platelets are of importance in the genesis of endothelial
      lesions leading to atherosclerosis, DFT was given to challenge leukocytosis in
      rabbits with diet-induced atherosclerosis (0.25% cholesterol for 16 weeks). After
      9 weeks of cholesterol feeding and at the end of experiment, oral DFT (60 mg/Kg
      per day) had decreased the leukocyte count raised by the cholesterol diet.
      Leukocyte stickiness and leukocyte differential counts were not modified by
      either oral cholesterol or by oral cholesterol plus oral DFT. At the end of
      experiment, oral DFT had normalized the platelet count increased by cholesterol
      diet. The red blood cell count decreased by oral cholesterol at 9 weeks and at
      the end of experiment was normalized by DFT. The % of aortae endothelial surface
      involved in the atherosclerotic process was decreased by oral DFT. The
      frequencies of intimal thickening in blood vessels of kidneys and hearts and in
      cardiac valves were reduced by oral DFT by 47%, 29% and 17%, although these
      reductions were not statistically significant. It is suggested that DFT, by
      preventing the increase in the number of leukocytes and platelets and
      deactivating them, as demonstrated in papers already published, was able to
      counteract against the atherosclerotic process.

PMID- 7623626
TI  - Contractile function of papillary muscles with carbonic anhydrase inhibitors.
AB  - Contractile parameters of directly stimulated rabbit papillary muscles were
      studied during incubation in baths containing the carbonic anhydrase inhibitors
      chlorzolamide (1*10(-3) M) or ethoxzolamide (1*10(-4) M). Both inhibitors caused
      an at least partly reversible decrease in isometric force as it has been observed
      in skeletal muscle, and--in contrast to the results in skeletal muscles--a
      decrease in time-to-peak and half-relaxation time. It is postulated that
      inhibition of the membrane-bound carbonic anhydrase of heart muscle might induce
      an intracellular acidosis and that this acidosis causes the observed effects on
      contractile parameters.

PMID- 7623627
TI  - Pyrogenic stimulation of vascular resistance in conscious sheep.
AB  - Increased arterial blood pressure following a pyrogenic reaction has been
      reported in previous studies, however the mechanism of this hypertension has not
      been examined in detail. The present study investigated the effects of both
      intravenous (IV) and intracerebroventricular (ICV) injection of
      lipopolysaccharide (LPS) from E. coli on body temperature (Tb), mean arterial
      pressure (MAP), heart rate (HR), cardiac output (CO), calculated total peripheral
      resistance (CTPR), stroke volume (SV) and plasma levels of adrenocorticotropin
      (ACTH) and arginine vasopressin (AVP) in conscious, chronically instrumented
      sheep. IV injection of LPS (1 microgram) increased Tb in a biphasic manner from
      38.7 +/- 0.1 to 39.5 +/- 0.2 degrees C after 50 min and to 39.9 +/- 0.2 degrees C
      after 130 min, and MAP increased biphasically from 64 +/- 1 to 70 +/- 4 mmHg
      after 40 min and to 78 +/- 3 mmHg after 130 min. CO initially decreased from 4.4
      +/- 0.1 to 3.5 +/- 0.1 after 40 min followed by a secondary rise to 4.8 +/- 0.1
      l/min after 100 min. This occurred together with a large, biphasic increase in
      CTPR from 14.5 +/- 1.0 to 22.0 +/- 2.0 mmHg/l/min at 40 min, and to 18.1 +/- 0.1
      mmHg/l/min at 120 min. HR increased from 68 +/- 4 to 97 +/- 4 b/min and SV
      decreased from 65 +/- 2 to 41 +/- 4 ml/beat during the first phase of activation.
      Plasma ACTH increased from 22 +/- 9 to 1043 +/- 175 pg/ml after 80 min, and
      plasma AVP increased from 0.7 +/- 0.2 to 12 +/- 4.0 pg/ml after 60 min. ICV
      injection of LPS produced a long-lasting increase in Tb and MAP, but had no
      effect on HR or plasma AVP. Plasma ACTH increased from 30 +/- 12 to 427 +/- 110
      pg/ml. These changes suggest that intravenous pyrogenic infection produces a
      potent vasoconstrictor action in sheep to increase blood pressure, possibly
      mediated by the actions of AVP within the CNS, or other pyrogenically released
      vasoconstrictor factors. Furthermore, the duration of activation of the
      cardiovascular system following peripheral and central LPS administration is
      different, which together with the contrasting effects on ACTH and AVP, indicate
      the involvement of several hypertensive mechanisms.

PMID- 7623628
TI  - The apparent affinity of morphine-3-glucuronide at mu1-opioid receptors results
      from morphine contamination: demonstration using HPLC and radioligand binding.
AB  - Equilibrium binding studies in sheep thalamic homogenates indicated that morphine
      3-glucuronide (M3G) had an apparent affinity for mu1-opioid binding sites (IC50 =
      178 +/- 40 nM, Ki = 116 +/- 25 nM, mean +/- s.e.m., n = 4) similar to that
      reported by Pasternak and co-workers (1). However, when the chemical purity of
      M3G was investigated using high-performance-liquid-chromatography (HPLC) with
      electrochemical detection, it was found to be contaminated with 0.5% (molar
      basis) of morphine. Reduction of the morphine contamination of M3G to 0.08%
      resulted in a 7.2-fold decrease in apparent binding affinity (IC50 = 1279 +/- 287
      nM, Ki = 766 +/- 30 nM, mean +/- s.e.m., n = 4), indicating that the small
      percentage of morphine present in the M3G raw material drug is the likely
      explanation for M3G's apparent binding to mu1-opioid receptors.

PMID- 7623629
TI  - Effect of the pyrrolizidine alkaloid, monocrotaline, on bile composition of the
      isolated, perfused rat liver.
AB  - Monocrotaline is a hepatotoxic pyrrolizidine alkaloid, releasing high levels of
      metabolites into bile of isolated, perfused liver. Although perfusion of rat
      liver with 0.5 mM monocrotaline does not affect bile flow over a 1 hr study
      period, it markedly affects bile composition. Biliary release of conjugated and
      free GSH increases 30-fold. Marked increases are also observed in the biliary
      concentration of the related sulfur-containing substances, cysteine and
      cysteinylglycine. However, biliary release of the sulfur amino acids, taurine and
      methionine, is unaffected. Only two amino acids show mildly increased releases,
      23% for glycine and 46% for aspartate. Release of bile acids, cholesterol and
      phospholipids also decrease, both in terms of mM concentration in bile and in
      terms of nmol secreted per g liver. Thus, exposure to monocrotaline causes
      disturbances in sulfur metabolism in the liver and in the composition of bile.
      The consequences of the digestive properties of bile and gastrointestinal
      toxicity remain to be established. As sulfhydryl compounds are involved in
      detoxification of monocrotaline metabolites, these findings indicate a mutual
      interaction of pyrrolizidine toxicity and sulfur metabolism. This suggests that
      dietary sulfur amino acid intake may influence susceptibility to pyrrolizidine
      poisoning.

PMID- 7623630
TI  - Child health care in Charles County, Maryland: a needs assessment.
AB  - In response to the perception of community leaders in Charles County, Maryland,
      that more health care services should be available for disadvantaged infants and
      young children in the county, an informal needs assessment was carried out.
      First, available public health statistical data were used to estimate the number
      of children under 10 years of age residing in low-income households without
      health insurance. Next, a household survey and a physician survey were used to
      determine community and professional attitudes regarding unmet child health care
      needs, barriers to care, and possible solutions. Survey results validate the
      existence of unmet health care needs of county children as well as support for a
      volunteer clinic to address these needs.

PMID- 7623631
TI  - Patient education: the risks associated with radiation exposure.

PMID- 7623632
TI  - Pertinent medical intelligence: fluoxetine's impact on sexual function.

PMID- 7623633
TI  - Case report: peritonitis complicating cone biopsy of the cervix.

PMID- 7623634
TI  - Stroke prevention.

PMID- 7623635
TI  - Spontaneous adrenal hemorrhage.

PMID- 7623636
TI  - Maryland physicians who helped make medical history: a portrait of Eugene H.
      Guthrie, M.D.

PMID- 7623637
TI  - The Baltimore General Dispensary: withhold not thine hand.

PMID- 7623638
TI  - Health care fraud and government investigators.

PMID- 7623639
TI  - [Development and design of specialized electrosurgical equipment for operations
      on human organs].
AB  - The paper outlines an original circuit of a basic electrosurgical apparatus (ESA)
      which is equipped with measuring informational transformers for automatic
      determination of load resistance (R1) and with a continuous memorizing device
      (CMD). Variants of ESA operating conditions are recorded in the CMD, depending
      upon the resistance of various particular human tissues. According to R1, one out
      of 8 areas of loading characteristics stored in the CMD is automatically chosen.
      A specializing principle for ESAs used in various fields has been proposed by
      using a basic model that has varying alteration ranges of R1.

PMID- 7623641
TI  - [Dermatological plastic surgery dye laser].
AB  - The paper deals with feasibility studies conducted to choose a laser for the
      treatment of vascular diseases causing skin hyperpigmentation. It describes a
      laser unit selectively acting on diseased vessels, which operates at a wavelength
      of 577 nm and at an energy density of 6-8 J/cm2 with pulse generation lasting at
      least 100 microseconds. In future the duration of pulse generation should be
      prolonged to 400 microseconds.

PMID- 7623640
TI  - [Superconducting magnetocardiographic systems].
AB  - A clinical superconducting magnetic cardiograph fit for the clinical setting has
      been designed on the basis of the investigations conducted.

PMID- 7623642
TI  - [Use of x-ray scanning densitometry and computerized tomography in the evaluation
      of the effect of tumor treatment].
AB  - The paper considers the ways of quantitative assessment of changes occurring in
      the density and size of a tumorous focus during its treatment (radiation,
      chemical and hormonal therapies). They are based on scanning densitometric
      techniques by identifying quantitative integral and differential parameters. The
      parameters are used to assess tissue alterations by applying computerized
      tomography. The investigations into the impact of radiation and chemotherapy on
      tumor tissue in breast and lung cancers have indicated that scanning densitometry
      and computerized tomography may be used to evaluate therapeutical effects.

PMID- 7623643
TI  - [Ionometric x-ray diagnostic devices].

PMID- 7623644
TI  - [Digital x-ray system (data collection, processing, storage and transmission of
      diagnostic information)].
AB  - The paper deals with the system that allows the conventional procedures for
      obtaining diagnostic X-ray images to be integrated with direct digital ones. It
      presents patterns of introducing digital roentgenography into practical medicine
      and describes the system how diagnostic X-ray images are obtained, processed,
      stored, and transmitted, which consists of automatic working places for X-ray
      laboratory assistant and an X-ray physician. The requirements for long-term
      diagnostic archives data base and for the software support of input of the data
      accompanying each X-ray film are discussed in the paper. The information
      presented reflects the authors' experience in using the system in a
      multidisciplinary hospital having an unselected stream of patients (n = 6,000).

PMID- 7623645
TI  - [Errors in the presentation of topometric data in radiotherapy planning systems].
AB  - Computer-aided simulation was used to assess the accuracy of calculating the
      effective radiological thickness in the system for planning radiation therapy
      while presenting anatomical data as a set of organ contours with various density
      areas. The data were compared with tomographic findings and the dependences of a
      calculation error upon the provision of a detailed specimen presentation were
      obtained. The effect of the complexity of a set of contours was studied and a
      dose error was calculated for typical therapy 60Co radiation beam.

PMID- 7623646
TI  - [Optical properties of Compoplast 300 polymer containers].
AB  - The paper presents the results of investigations into the spectral wall
      transmission ratio of Compoplast 300 containers, which have been made on a SF-46
      spectrophotometer in a wavelength of 190 to 1100 nm. It is concluded that it
      should be borne in mind the fact that a part of radiation is absorbed by the
      container walls while developing the photomodification conditions of
      hemocomponents. The authors emphasize that the manufacture of hemocontainers made
      from the polymer materials which have a high ultraviolet radiation transmission
      ratio is very promising.

PMID- 7623647
TI  - [Current problems of medical physics in the radionuclide diagnosis].
AB  - The most important problems of medical physics in clinical radionuclide diagnosis
      are considered on the basis of the data available in the literature. The matter
      and trends in the development of investigations, into radiopharmaceutical, hard-
      and software, methodological, and algorithmic supports of radionuclide diagnosis,
      as well as those into its quality insurance and provision of radiation safety of
      patients and the personnel are also analyzed.

PMID- 7623648
TI  - [A gastric probe].

PMID- 7623649
TI  - [Compact eye tonometer-tonograph, TON-1].

PMID- 7623650
TI  - [Medical stimulators for biological feedback].
AB  - The fact that a physiological function generally unconsciously controlled can be
      self-regulated was demonstrated as long as 20 years ago. The biological feedback
      (BF) is the back return of information to a man or an animal on the function of
      their viscera and systems. BF is a process that through audible or visual signals
      transmits long-term routine information on physiological reactions and
      parameters, such as blood pressure and skin temperature, which are uncontrollable
      by an individual's consciousness and generally recorded by noninvasive
      techniques. Biological controlling techniques and procedures are used for the
      treatment and rehabilitation of a wide range of diseases and nosological entities
      -- from migraine to AIDS and cancer mainly in the USA, less in Western Europe,
      and incomparably little in the CIS countries. The Novosibirsk Institute of
      Medical and Biological Cybernetics, Siberian Branch of the Russian Academy of
      Medical Sciences is working at biological controlling problems, by making
      researches, investigations, clinical studies and developments of stimulators for
      BF.

PMID- 7623651
TI  - [A light-scattering spectrometer for medical diagnostic tasks].
AB  - Whether a high-resolving light scattering spectrometer may be used in medical
      practice is discussed in the paper. The results of the experiments on blood
      components and microorganisms are discussed.

PMID- 7623652
TI  - In-hospital cardiopulmonary resuscitation. Survival in 1 hospital and literature
      review.
AB  - Cardiopulmonary resuscitation (CPR) has been used extensively in the hospital
      setting since its introduction over 3 decades ago. We reviewed the CPR records at
      1 hospital during a 2-year period and the results from 113 published reports of
      inpatient CPR with a total patient population of 26,095. We compared the survival
      rates of patients following CPR and the pre-arrest and intra-arrest factors
      related to survival. At the hospital where CPR records were reviewed, 44% of
      patients initially survived following CPR, and the 1-year survival rate was 5%.
      Patients with shorter durations of CPR and those administered fewer procedures
      and medications during CPR survived longer than patients with prolonged CPR.
      Patients with witnessed cardiac arrests were more likely to survive than those
      with unwitnessed arrests. Also, patients with respiratory arrests had much better
      survival than patients with cardiopulmonary arrests. Worldwide, 113 studies
      showed a survival to discharge rate of 15.2% (United States = 15%, Canada = 16%,
      United Kingdom = 17%, other European countries = 14%). Patients were more likely
      to survive to discharge if they were treated in a community hospital (versus a
      teaching or Veterans Affairs hospital) or were younger. Patients with ventricular
      tachycardia or fibrillation were more likely to survive than those with asystole
      or electromechanical dissociation. Patient's location was related to outcome,
      with emergency room and coronary care unit patients more likely to survive than
      intensive care unit and general ward patients. Other factors related to better
      survival rates were respiratory arrest, witnessed arrest, absence of comorbidity,
      and short duration of CPR. Knowledge of the likelihood of survival following CPR
      for subgroups of the hospital population based on pre-arrest and intra-arrest
      factors can help patients, their families, and their physicians decide, with
      compassion and conviction, in what situations CPR should be administered.

PMID- 7623653
TI  - Group B streptococcal bacteremia in adults. Five years' experience and a review
      of the literature.
AB  - The importance of group B streptococcus (GBS) as a cause of serious infectious
      disease among adults is not widely appreciated. In adults, the modes of
      acquisition and transmission are unknown. Since most hospital-based studies of
      GBS bacteremia in adults consist of small numbers of patients, the clinical
      spectrum of disease is not well described. Our retrospective study reviews the
      clinical features, antimicrobial therapy, and risk factors for mortality of 32
      adult patients (18 women and 14 men) with GBS bacteremia and compares the
      proportion of isolates from the different beta-hemolytic streptococci sero
      groups. We found that 39% of isolates from adult blood cultures were group B, a
      frequency nearly identical to that of group A streptococcal bacteremia. Most
      (66%) adult patients were more than 50 years old. Primary bacteremia was the most
      frequent clinical diagnosis, occurring in 7 (22%) of 32 patients. Nonhematologic
      cancer was the most frequently associated condition (25%). Nineteen percent of
      the patients had diabetes mellitus. The overall mortality rate was 31% and was
      significantly associated with increasing age. Our results are compared to those
      obtained by a review of all 5 previous comparable studies and demonstrate that
      GBS bacteremia is a serious infection in adults with increased mortality related
      to advancing age.

PMID- 7623654
TI  - An analysis of 110 serious enterococcal infections. Epidemiology, antibiotic
      susceptibility, and outcome.
AB  - A prospective, observational study of 110 patients with serious infections due to
      Enterococcus spp. in 6 university and community teaching hospitals in Connecticut
      was conducted to define the epidemiology of community and nosocomial serious
      enterococcal infections and to determine risk factors, including antibiotic
      resistances, that contribute to outcome. Serious community and nosocomial
      enterococcal infections involved a variety of sites, and antibiotic resistance
      was common. Types of infection by major organ system were cardiovascular, 54%
      (catheter-related bacteremia 28%, primary bacteremia 18%, endocarditis 6%, septic
      thrombophlebitis 1%); intra-abdominal, 13% (including cholangitis, 6%); renal,
      13%; skin and soft tissue, 5%; bone and joint, 4%; pleuropulmonary, 4%; central
      nervous system, 3%; deep surgical wound, 3%; and endometritis, 2%. Sixty-one
      percent of infections were nosocomial; 48% of these occurred in the intensive
      care unit. Enterococcus faecium was responsible for 20% of all infections.
      Antibiotic resistances among the infections included high-level gentamicin
      resistance (26%), ampicillin resistance (10%), and vancomycin resistance (8%).
      Clinical cure was achieved in 64% of patients; 6.8% of patients relapsed, 6.8%
      had recurrence of the infection with a different pathogen, and overall mortality
      was 23%. Ampicillin resistance and a high acute physiology and chronic health
      evaluation (APACHE) II score were highly predictive of lack of cure.

PMID- 7623655
TI  - Cryptogenic organizing pneumonia. A report of 25 cases and a review of the
      literature.
AB  - Cryptogenic organizing pneumonia (COP), also known as bronchiolitis obliterans
      organizing pneumonia (BOOP), is an uncommon lung disease characterized by the
      presence of granulation tissue within the alveolar ducts and alveoli. Because of
      the limited published literature on this topic and limited information on outcome
      we reviewed our own experience over an 8-year period and also critically
      evaluated the literature. We reviewed all cases of COP diagnosed from 1985
      through 1992 at Vancouver General Hospital: 25 patients (14 male, 11 female) aged
      20-77 years (mean, 49 yr, SD +/- 17 yr). Nine patients had myeloproliferative
      disorder, including 6 who had allogenic bone marrow transplants; 2 patients had
      connective tissue disease; and 14 patients had no underlying disease
      (idiopathic). Data retrieved retrospectively from clinical records included
      demographics, risk factors, symptoms, chest radiographs, computerized tomograms,
      lung function tests, therapy prescribed, and response to therapy. Symptoms
      included dyspnea and cough (n = 15) (60%), cough only (n = 10) (40%), and fever
      (n = 15) (60%). Twenty-two patients were diagnosed by open lung biopsy and 3 by
      transbronchial biopsy. Lung imaging showed bilateral patchy airspace
      consolidation or nodular opacities as the main finding in 22 patients. Pulmonary
      function tests showed a combined restrictive and obstructive pattern. All
      patients received prednisone therapy except 1 patient whose idiopathic findings
      resolved completely with minimal treatment. Eight patients died, including 4 of
      the 9 patients with myeloproliferative disorder--2 from a combination of
      respiratory failure due to COP and graft-versus-host disease. One of 2 patients
      with connective tissue disease died, and 3 of 14 patients with idiopathic COP
      died. COP is an uncommon condition but should be considered in patients with
      bilateral airspace disease, especially those who fail to respond to antibiotics
      for presumed pneumonia. Although pulmonary function tests and CT scan findings in
      conjunction with the clinical features usually suggest the diagnosis, definite
      confirmation usually requires either open lung biopsy or transbronchial biopsy.
      Histologic confirmation of the diagnosis is particularly warranted as therapy
      with corticosteroids is usually needed for a number of months. The prognosis is
      excellent with idiopathic cases but more guarded especially when COP is
      associated with lymphoproliferative or connective tissue disease.

PMID- 7623656
TI  - Correlates of hepatitis C virus infections among injection drug users.
AB  - Injection drug users are at high risk for hepatitis C virus (HCV) infection. In
      Baltimore, Maryland, the prevalence of anti-HCV is greater among injection drug
      users who are black, human immunodeficiency virus (HIV) infected, have injected
      longer, have injected more frequently, and have injected cocaine than among other
      injection drug users. HCV infection occurs quickly after the initiation of
      injecting illicit drugs, with 78% of study participants anti-HCV positive after 2
      years of injecting. The prevalence of anti-HCV among injection drug users does
      not appear to be related to socioeconomic factors or sexual practices. Some
      injection drug users remain free of anti-HCV even after years of injecting and
      serologic evidence of other bloodborne pathogens. Some of these injection drug
      users have HCV infection, demonstrated by HCV RNA in their sera. However, the
      basis for viral persistence in the absence of anti-HCV and for the absence of HCV
      infection in long-term drug users is not known. Further studies are indicated to
      determine the mechanism or mechanisms for the absence of anti-HCV in persons
      exposed to the virus, because the biologic basis for this condition may elucidate
      the elements missing in the immune response of the majority of HCV-exposed
      persons who acquire persistent infection. In addition, interventions to prevent
      HCV infections should be applied in populations at risk for injection drug use
      early or before drug use begins.

PMID- 7623657
TI  - Interspecies recombination in nature: a meningococcus that has acquired a
      gonococcal PIB porin.
AB  - A vaginal isolate of Neisseria has been reported to resemble Neisseria
      meningitidis in biochemical characteristics but to react with serological
      reagents that are specific to the PI porin from Neisseria gonorrhoeae. We have
      confirmed that this isolate has the biochemical attributes of a meningococcus and
      have shown that it clusters among meningococcal isolates on a dendrogram based on
      isoenzyme variation within housekeeping enzymes from populations of N.
      meningitidis and N. gonorrhoeae. Furthermore, the sequences of the fbp and adk
      genes were typical of those of N. meningitidis and were distinct from those of N.
      gonorrhoeae. However, the porB gene was very similar to the por genes of N.
      gonorrhoeae isolates that express the PIB class of outer-membrane porin
      (differing from one gonococcal por allele at only a single nucleotide site), and
      was clearly distinct from the porB genes of N. meningitidis. The isolate
      therefore appears to be a typical meningococcus, except that its porB gene has
      been replaced with the por gene from a gonococcus.

PMID- 7623658
TI  - Effect of inhA and katG on isoniazid resistance and virulence of Mycobacterium
      bovis.
AB  - Isoniazid (INH) resistance of the Mycobacterium tuberculosis Complex (MtbC) is
      associated with both loss of catalase activity and mutation of the inhA gene.
      However, the relative contributions of these changes to resistance and to the
      loss of virulence for guinea-pigs is unknown. In this study, a virulent strain of
      Mycobacterium bovis, a member of the MtbC, was exposed to increasing
      concentrations of INH. Two INH-resistant strains were produced which had lost
      catalase activity. Strain WAg405, which had a higher resistance to INH, also had
      a mutation in the inhA gene. This demonstrated that loss of catalase activity and
      mutation of inhA had a cumulative effect on INH resistance. When a functional
      katG gene was integrated into the genome of WAg405 the INH resistance was greatly
      reduced. This indicated that most of the resistance had been caused by loss of
      catalase activity. While the parent INH-sensitive strain was virulent for guinea
      pigs, the INH-resistant strains were significantly less virulent. Integration of
      a functional katG gene into the most resistant strain restored full virulence.
      This clearly established that katG is a virulence factor for M. bovis and that
      mutation of the inhA gene has no effect on virulence.

PMID- 7623659
TI  - F plasmid CcdB killer protein: ccdB gene mutants coding for non-cytotoxic
      proteins which retain their regulatory functions.
AB  - The ccd locus of the F plasmid codes for two gene products, CcdA and CcdB, which
      contribute to the plasmid's high stability by post-segregational killing of
      plasmid-free bacteria. Like the quinolones, the CcdB protein is a poison of the
      DNA-topoisomerase II complexes, while CcdA acts as an antidote against CcdB. In
      addition to these poison-antipoison properties, the CcdA and CcdB proteins act
      together at transcription level to repress their own synthesis. In this work, we
      have isolated, in vivo, and characterized several non-killer CcdB mutants. All
      missense mutations which inactivate CcdB killer activity are located in the
      region coding for the last three C-terminal residues. However, the resulting
      mutant CcdB proteins retain their autoregulatory properties. We conclude that the
      last three C-terminal residues of CcdB play a key role in poisoning but are not
      involved in repressor formation.

PMID- 7623660
TI  - Molecular population genetic analysis of the enn subdivision of group A
      streptococcal emm-like genes: horizontal gene transfer and restricted variation
      among enn genes.
AB  - The group A streptococcal emm-like genes, which encode the cell-surface M and M
      like proteins, are divided into distinct mrp, emm and enn subdivisions and are
      clustered together in a region of the chromosome called the vir regulon. In order
      to understand the mechanisms involved in the evolution of emm-like genes, a 180
      bp fragment of the 5' variable region of the enn gene was characterized in 31
      strains for which emm sequences and multilocus enzyme electrophoretic profiles
      have been previously determined. The results demonstrate that nucleotide
      polymorphisms at the enn locus are generated predominantly by point mutations and
      short deletions or insertions, and that variation among enn and emm genes has
      arisen by similar mechanisms. However, diversity at the enn locus is restricted
      in comparison to the emm locus. Moreover, there is strong evidence for intragenic
      recombination at the enn locus and the pattern of distribution of emm and enn
      alleles among strains suggests that these genes may be independently acquired by
      horizontal transfer and recombination from distinct donor strains, thereby
      generating a mosaic structure for the vir regulon. The results add to a growing
      body of evidence that horizontal gene transfer has played a major role in the
      evolution of Streptococcus pyogenes vir regulons.

PMID- 7623661
TI  - Protein kinase-dependent HPr/CcpA interaction links glycolytic activity to carbon
      catabolite repression in gram-positive bacteria.
AB  - CcpA, the repressor/activator mediating carbon catabolite repression and glucose
      activation in many Gram-positive bacteria, has been purified from Bacillus
      megaterium after fusing it to a His tag. CcpA-his immobilized on a Ni-NTA resin
      specifically interacted with HPr phosphorylated at seryl residue 46. HPr, a
      phospho-carrier protein of the phosphoenolpyruvate: glycose phosphotransferase
      system (PTS), can be phosphorylated at two different sites: (i) at His-15 in a
      PEP-dependent reaction catalysed by enzyme I of the PTS; and (ii) at Ser-46 in an
      ATP-dependent reaction catalysed by a metabolite-activated protein kinase.
      Neither unphosphorylated HPr nor HPr phosphorylated at His-15 nor the doubly
      phosphorylated HPr bound to CcpA. The interaction with seryl-phosphorylated HPr
      required the presence of fructose 1,6-bisphosphate. These findings suggest that
      carbon catabolite repression in Gram-positive bacteria is a protein kinase
      triggered mechanism. Glycolytic intermediates, stimulating the corresponding
      protein kinase and the P-ser-HPr/CcpA complex formation, provide a link between
      glycolytic activity and carbon catabolite repression. The sensitivity of this
      complex formation to phosphorylation of HPr at His-15 also suggests a link
      between carbon catabolite repression and PTS transport activity.

PMID- 7623662
TI  - L5 luciferase reporter mycobacteriophages: a sensitive tool for the detection and
      assay of live mycobacteria.
AB  - Recombinant bacteriophages provide efficient delivery systems for introducing
      reporter genes into specific bacterial hosts. We have constructed
      mycobacteriophage L5 recombinants carrying the firefly luciferase gene inserted
      into the tRNA region of the phage genome. Infection of Mycobacterium smegmatis by
      these phages results in expression of the luciferase gene and light emission.
      Fortuitously, the luciferase gene is expressed continuously in lysogens surviving
      infection. Synthesis of luciferase from a mycobacterial promoter created by
      cloning enables the detection of extremely small numbers of M. smegmatis cells.
      These reporter phages can be used to discriminate between drug-sensitive and drug
      resistant strains of M. smegmatis, and may provide tools for the rapid
      identification and classification of antimycobacterial agents.

PMID- 7623663
TI  - Mutations in the chemotactic response regulator, CheY, that confer resistance to
      the phosphatase activity of CheZ.
AB  - CheY, a small cytoplasmic response regulator, plays an essential role in the
      chemotaxis pathway. The concentration of phospho-CheY is thought to determine the
      swimming behaviour of the cell: high levels of phospho-CheY cause bacteria to
      rotate their flagella clockwise and tumble, whereas low levels of the
      phosphorylated form of the protein allow counter-clockwise rotation of the
      flagella and smooth swimming. The phosphorylation state of CheY in vivo is
      determined by the activity of the phosphoryl donor CheA, and by the antagonistic
      effect of dephosphorylation of phospho-CheY. The dephosphorylation rate is
      controlled by the intrinsic autohydrolytic activity of phospho-CheY and by the
      CheZ protein, which accelerates dephosphorylation. We have analysed the effect of
      CheZ on the dephosphorylation rates of several mutant CheY proteins. Two point
      mutations were identified which were 50-fold and 5-fold less sensitive to the
      activity of CheZ than was the wild-type protein. Nonetheless, the phosphorylation
      and autodephosphorylation rates of these mutants. CheY23ND and CheY26KE, were
      observed to be identical to those of wild-type CheY in the absence of CheZ. These
      are the first examples of cheY mutations that reduce sensitivity to the
      phosphatase activity of CheZ without being altered in terms of their intrinsic
      phosphorylation and autodephosphorylation rates. Interestingly, the residues Asn
      23 and Lys-26 are located on a face of CheY far from the phosphorylation site
      (Asp-57), distinct from the previously described site of interaction with the
      histidine kinase CheA, and partially overlapping with a region implicated in
      interaction with the flagellar switch.

PMID- 7623664
TI  - Iron regulation of siderophore biosynthesis and transport in Pseudomonas putida
      WCS358: involvement of a transcriptional activator and of the Fur protein.
AB  - Pseudobactin 358 is the yellow-green fluorescent siderophore produced by
      Pseudomonas putida WCS358 in conditions of iron limitation. The genes encoding
      for siderophore biosynthesis are iron-regulated at the transcriptional level.
      Previous work has shown that a positive regulator, PfrA, is absolutely required
      for the activation under iron-limiting conditions of pseudobactin 358
      biosynthesis. In this study we identified a set of Tn5 insertion mutants of
      strain WCS358 which lost the ability to activate an iron-regulated siderophore
      promoter. These mutants no longer produced pseudobactin 358. Molecular analysis
      revealed that they carried a Tn5 insertion in a gene, designated pfrl
      (Pseudomonas ferric regulator), which codes for a protein (Pfrl) of 19.5 kDa.
      Pfrl contains a putative helix-turn-helix motif typical of DNA-binding proteins
      and has homology to two DNA-binding transcriptional activators, Fecl from
      Escherichia coli and Pupl from P. putida. The proposed role of Pfrl in strain
      WCS358 is an activator protein regulating pseudobactin 358 biosynthesis under
      iron limitation. The pfrl promoter region contains a sequence which displays high
      identity to the Fur-box consensus. This 19 bp consensus sequence is recognized by
      Fur, an iron-binding repressor protein found in many different bacteria. The E.
      coli Fur protein can bind to the pfrl promoter region, indicating that this
      activator gene is likely to be iron-regulated by Fur. We also report the
      identification and characterization of the P. putida WCS358 fur gene. The Fur
      protein of strain WCS358 is structurally and functionally similar to other cloned
      Fur proteins from other bacterial species.

PMID- 7623666
TI  - Molecular genetics of a chromosomal locus involved in copper tolerance in
      Escherichia coli K-12.
AB  - The cutA locus, presumably involved in copper tolerance in Escherichia coli, was
      characterized by a mutation leading to copper sensitivity. Copper-accumulation
      measurements with radioactive 64Cu2+ showed increased uptake by cutA copper
      sensitive mutant cells, and reduced uptake when the cutA mutation was
      complemented in trans. The locus was mapped using complementation of the cutA
      mutant to partial copper tolerance with wild-type chromosomal fragments. The 3.2
      kb DNA region involved in cutA was sequenced and analysed, revealing three
      significant open reading frames, none of which had been previously published. The
      products of all three open reading frames were identified, when synthesized with
      the T7 phage promoter expression system, as polypeptides of about 50 kDa, 24 kDa,
      and 13 kDa, consistent with the sizes predicted from the DNA sequences. The 50
      kDa and 24 kDa polypeptides were found in the bacterial inner membrane, and the
      13 kDa polypeptide with the cytoplasmic fraction. In addition to being required
      for copper tolerance, cutA affects tolerance levels to zinc, nickel, cobalt and
      cadmium salts. Transcriptional fusions of cutA with the lux operon showed
      induction by copper, zinc, nickel, cobalt and, to a lesser extent, cadmium,
      manganese and silver salts.

PMID- 7623665
TI  - The hrp gene locus of Pseudomonas solanacearum, which controls the production of
      a type III secretion system, encodes eight proteins related to components of the
      bacterial flagellar biogenesis complex.
AB  - Five transcription units of the Pseudomonas solanacearum hrp gene cluster are
      required for the secretion of the HR-inducing PopA1 protein. The nucleotide
      sequences of two of these, units 1 and 3, have been reported. Here, we present
      the nucleotide sequence of the three other transcription units, units 2, 4 and 7,
      which are together predicted to code for 15 hrp genes. This brings the total
      number of Hrp proteins encoded by these five transcription units to 20, including
      HrpB, the positive regulatory protein, and HpaP, which is apparently not required
      for plant interactions. Among the 18 other proteins, eight belong to protein
      families regrouping proteins involved in type III secretion pathways in animal
      and plant bacterial pathogens and in flagellum biogenesis, while two are related
      solely to proteins involved in secretion systems. For the various proteins found
      to be related to P. solanacearum Hrp proteins, those in plant-pathogenic bacteria
      include proteins encoded by hrp genes. For Hrp-related proteins of animal
      pathogens, those encoded by the spa and mxi genes of Shigella flexneri and of
      Salmonella typhimurium and by the ysc genes of Yersinia are involved in type III
      secretion pathways. Proteins involved in flagellum biogenesis, which are related
      to Hrp proteins of P. solancearum, include proteins encoded by fli and flh genes
      of S. typhimurium, Bacillus subtilis and Escherichia coli and by mop genes of
      Erwinia carotovora. P. solanacearum Hrp proteins were also found to be related to
      proteins of Rhizobium fredii involved in nodulation specificity.

PMID- 7623667
TI  - The biogenesis of c-type cytochromes in Escherichia coli requires a membrane
      bound protein, DipZ, with a protein disulphide isomerase-like domain.
AB  - A mutant of Escherichia coli K-12, JCB606, which lacks all five c-type
      cytochromes synthesized during anaerobic growth in the presence of nitrite or
      trimethylamine-N-oxide (TMAO), was totally defective in Nrf activity and also
      partially defective in TMAO reductase activity. The mutation in strain JCB606 was
      shown to affect expression of the tor operon, which contributes almost equally
      with the products of the dms operon to the rate of TMAO reduction by bacteria
      during anaerobic growth in the presence of TMAO. The mutation in strain JCB606,
      dipZ, was mapped by P1 transduction close to the mel operon at co-ordinate 4425
      on the E. coli chromosome, the gene order being nrf-fdhF-mel-dipZ-ampC.
      Recombinant plasmids that restored Nrf activity to test-tube cultures of the
      mutant were isolated from a cosmid library. A 2.7 kb EcoRV-SmaI fragment (co
      ordinates 4443 to 4446 kb on the physical map of the E. coli chromosome) was
      found potentially to encode three genes arranged in at least two operons. The
      second gene, dipZ, was sufficient to complement the JCB606 mutation. The
      translated DNA sequence predicts that DipZ is a 53 kDa integral membrane protein
      with a 37 kDa N-terminal domain including at least six membrane-spanning helices
      and a 16 kDa carboxy-terminal hydrophilic domain which includes a protein
      disulphide isomerase-like motif. It is suggested that DipZ is essential for
      maintaining cytochrome c apoproteins in the correct conformations for the
      covalent attachment of haem groups to the appropriate pairs of cysteine residues.

PMID- 7623669
TI  - Identification of errors among database sequence entries and comparison of
      correct amino acid sequences for the heat-labile enterotoxins of Escherichia coli
      and Vibrio cholerae.

PMID- 7623668
TI  - Treponema pallidum in gel microdroplets: a novel strategy for investigation of
      treponemal molecular architecture.
AB  - Controversy exists regarding the constituents and antigenic properties of the
      Treponema pallidum outer membrane; a major point of contention concerns the
      cellular location(s) of the spirochaete's lipoprotein immunogens. To address
      these issues and circumvent problems associated with prior efforts to localize
      treponemal surface antigens, we developed a novel strategy for investigating T.
      pallidum molecular architecture. Virulent treponemes were encapsulated in porous
      agarose beads (gel microdroplets) and then probed in the presence or absence of
      Triton X-100. Intact, encapsulated treponemes were not labelled by monospecific
      antisera directed against four major T. pallidum lipoproteins or a candidate T.
      pallidum outer membrane protein (TpN50) with C-terminal sequence homology to
      Escherichia coli OmpA or by human or rabbit syphilitic serum. Each of these
      immunologic reagents, however, labelled encapsulated treponemes co-incubated with
      detergent. In contrast, antibodies generated against isolated T. pallidum outer
      membranes labelled intact organisms and the pattern of fluorescence was
      consistent with the distribution of rare outer membrane proteins visualized by
      freeze-fracture electron microscopy. In addition to providing strong evidence
      that the protein portions of treponemal lipoproteins are located within the
      periplasmic space, these studies have extended our understanding of the
      topographical relationships among T. pallidum cell envelope constituents. They
      also demonstrate the feasibility of generating antibodies against rare outer
      membrane proteins and detecting them on the surfaces of virulent treponemes.

PMID- 7623671
TI  - Young children's communication and literacy: a qualitative study of language in
      the inclusive preschool.
AB  - Interactive and literacy-based language use of young children within the context
      of an inclusive preschool classroom was explored. An interpretivist framework and
      qualitative research methods, including participant observation, were used to
      examine and analyze language in five preschool classes that were composed of
      children with and without disabilities. Children's language use included spoken,
      written, signed, and typed. Results showed complex communicative and literacy
      language use on the part of young children outside conventional adult
      perspectives. Also, children who used expressive methods other than speech were
      often left out of the contexts where spoken language was richest and most
      complex.

PMID- 7623670
TI  - Analysis of a chemotaxis operon in Rhizobium meliloti.
AB  - Genes controlling chemotaxis towards L-amino acids and D-mannitol in Rhizobium
      meliloti have been identified by Tn5 insertions that lead to chemotaxis-deficient
      mutants. The tagged genes span an 8.7 kbp region that has been sequenced. These
      genes are part of a large operon containing three novel open reading frames,
      orf1, orf2 and orf9, and six familiar chemotaxis (che) genes, cheY1-cheA-cheW
      cheR-cheB-cheY2, that have been assigned by their similarity to known Escherichia
      coli genes. The second copy of cheY may be part of a second signalling chain;
      orf1 and orf2 encode sequence motifs that resemble the signalling domain of E.
      coli MCPs (methyl-accepting chemotaxis proteins), while the product of orf9 may
      contain a transmembrane domain. No protein methylation has been observed in
      Rhizobium meliloti in response to L-amino acids. However, the presence of cheR
      (methyltransferase gene) and cheB (methylesterase gene) suggested that MCPs are
      likely components of the chemotactic response in R. meliloti. Therefore, it is
      postulated that two chemotaxis pathways are functional in R. meliloti: one
      responds to L-amino acids via ORF1-ORF2, whereas the other (probably responding
      to specific plant exudates) acts via MCP-like receptors, and both interact with
      the central components CheW-CheA-CheY1 and/or CheY2.

PMID- 7623672
TI  - Social workers' perceptions of older parents caring at home for sons and
      daughters with developmental disabilities.
AB  - Members of the American Association on Mental Retardation (AAMR) Social Work
      Division (N = 395) were surveyed to determine their perceptions of their role in
      assisting older parents in permanency planning. Practitioners, administrators,
      and educators similarly perceived ease in counseling aging families, but also
      noted their need for additional resources and specialized training. Written
      comments revealed (a) that the system must do more; (b) older parents are seen as
      different from other parents, with practitioners concerned about dependency in
      these parents' relationships with their sons and daughters and administrators
      attributing differences to past adverse system interactions; (c) parents old and
      young are alike in many ways; and (d) siblings should be involved in family
      caregiving. Recommendations were made with regard to meeting the special needs of
      older families, reducing "blaming" attitudes among social workers, and expanding
      best practice knowledge.

PMID- 7623673
TI  - An "if this, then that" formulation of decisions related to social role
      valorization as a better way of interpreting it to people.
AB  - Social Role Valorization is interpreted as a high-order empirical social science
      theory that informs people about the relation between the social roles that
      people hold and what happens to them as a result and how to valorize (improve or
      defend) the social roles of people at risk of social devaluation. Because Social
      Role Valorization is not a "religion," people must go to higher belief systems to
      determine whether and why other humans should be valued or devalued, whether the
      social valuation of others should be promoted, and which presumably effective
      means to this end are morally defensible or even imperative. Whether a pursuit of
      social valuation in certain cases has unacceptable implications can be in the
      domain of either "religion" or practical trade-offs.

PMID- 7623674
TI  - A peaceful coexistence? State MR/DD agency trends in integrated employment and
      facility-based services.
AB  - National survey data reported by state MR/DD agencies for integrated and
      segregated employment and facility-based nonwork services provided during FYs
      1988 and 1990 were examined. The percentage and total number of individuals in
      integrated employment grew significantly across the 2 years. However, there were
      no significant changes in the percentage or number served in facility-based
      settings. State MR/DD agencies continue to fund a dual service system, with the
      vast percentage of total resources allocated to segregated programs. Policy and
      funding incentives need to be developed to stimulate conversion of segregated
      services to integrated employment.

PMID- 7623675
TI  - Services for adult family members with mental retardation: perceptions of
      accessibility and satisfaction.
AB  - Caregivers' satisfaction with and perceptions of the services received by their
      adult family member with mental retardation were examined. Most caregivers were
      satisfied with the services, regardless of the type of services received. Access
      variables, including the assistance provided in acquiring services, were better
      predictors of satisfaction than were aspects of the services. Demographic
      variables did not predict ratings of accessibility or satisfaction.

PMID- 7623676
TI  - Acquisition and generalization of social skills by high school students with mild
      mental retardation.
AB  - Initial acquisition of social skills by high school students with mild mental
      retardation was measured during the social skills training game Stacking the
      Deck. Generalization probes were conducted outside of the training setting
      (immediately preceding and following training, and 6 weeks posttraining). Due to
      the high degree of dissimilarity between stimuli in and outside of the training
      setting, we hypothesized that generalization of skills to nontraining
      environments would be minimal. Two replications of an initial single-case study
      were conducted. Students demonstrated acquisition of social skills across game
      conditions. Immediate generalization of trained social skills did not occur. A
      possible "deferred generalization" effect was evidenced at 6 weeks posttraining.
      Results were discussed with respect to the "integrity of common stimuli" and
      opportunities to respond.

PMID- 7623677
TI  - Where, oh where, has common sense gone? (Or if the shoe don't fit, why wear it?)

PMID- 7623678
TI  - For whom the bell curves: old texts, mental retardation, and the persistent
      argument.

PMID- 7623679
TI  - A response to the ACME-TRI report: the Dalhousie problem-based learning
      curriculum.
AB  - With the class of 1996, Dalhousie University Faculty of Medicine instituted a
      totally revised curriculum. The revisions transformed an entirely traditional
      curriculum to a student-centred curriculum, which is based on learning in
      context, and incorporates a problem-based approach to the entire curriculum. This
      paper describes our experience in the actual implementation of our revised
      curriculum, in the context of the Association of American Medical Colleges
      Assessing Change in Medical Education--The Road to Implementation (ACME-TRI)
      Report.

PMID- 7623680
TI  - Entry to medical school: an audit of traditional selection requirements.
AB  - The major focus in the selection of entrants for medical school has traditionally
      been on academic achievement in school-leaving examinations in which certain
      science subjects are a requirement. A longitudinal study of 413 successful
      applicants was undertaken to determine the relationship of these admission
      criteria to subsequent performance. The findings support a correlation between
      overall marks in the school-leaving examination and the annual Grade Point
      Averages. Those students in the top quartile for marks showed a significant
      advantage in terms of achievement but only in the preclinical years. Despite the
      significant correlations no predictions could be made on the basis of overall
      marks. No correlation was found with levels of clinical competence during the
      ward clerkships or with the interdisciplinary objective structured clinical
      examination (OSCE) in the final examination. Marks in individual school-leaving
      examination subjects correlated with performance during different parts of the
      course but only those entrants in the top quartile for marks in physics and
      biology showed an advantage through to the clinical years. English marks were the
      least correlated and failed to confer an advantage in any year of the course.
      None of the correlations between school-leaving marks and grades in medical
      school exceeded 0.4. The predictive value of school-leaving examination marks
      therefore accounted for only 16% of the variance in subsequent examinations.
      Selection of medical students on the basis of academic criteria alone is
      inadequate and should be accompanied by assessment of personal qualities. This
      School no longer uses school-leaving marks as the primary selection
      instrument.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7623681
TI  - Ethical reasoning and decision-making in the clinical setting: assessing the
      process.
AB  - Clinical ethical reasoning and analysis are skills as central to good patient
      care as the efficient application of biomedical knowledge to diagnosis and
      prognosis. However, experience in teaching clinical ethics to senior medical
      students has indicated that simply trying to 'apply' the knowledge learnt about
      ethical theories, principles, concepts and rules in the clinical setting does not
      ensure ethical competence in clinical decision-making. In 1992, we developed and
      piloted a three-session programme that focused on a more systematic approach to
      the way students identified and attempted to manage ethical issues in their
      clinical practice. This programme was modified and improved in 1993 and further
      expanded in 1994. Our experience suggests that many students are now better able
      to bridge what has been called the 'gap' between the possession of ethical
      knowledge and its actual use in clinical decision-making. The remaining problem
      was assessment. How do you assess clinical ethical reasoning and decision-making?
      In the preclinical years of medical education, knowledge-based assessment tools,
      like the modified essay question (MEQ), provide a means for assessing the
      sensitivity of students to ethical issues. However, such tools permit neither an
      appraisal of how students actually make clinical ethical decisions, nor which
      factors students perceive as important in making an actual clinical decision. In
      order to make this type of appraisal, we developed a format for a written case
      report that facilitated our assessing the process as well as the end-product, the
      decision.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7623682
TI  - Medical education in the light of the World Health Organization Health for All
      strategy and the European Union.
AB  - Most governments and health professionals clearly recognize that the education of
      professionals must be adapted to practice in order to meet the needs of the
      population and of health systems. The role of medical schools, in a world where
      specialization is becoming a requirement to practice and is highly regulated,
      needs to be redefined. Medical schools need to transform their specialist
      training into a community-oriented, generalist education. In this light, the
      article analyses the European Union directives on medical education, and the
      recommendations of the World Health Organization (to meet the challenges of the
      Health for All Policy) and the World Federation for Medical Education. All are
      designed to reorient medical education to meet the health needs of the
      population, to reduce health costs, to ensure quality and to permit the free
      movement of sufficiently qualified health professionals.

PMID- 7623683
TI  - Ethics in the clinic: a comparison of two Dutch teaching programmes.
AB  - This paper compares ethics programmes in clinical education in two medical
      schools in the Netherlands. Ethics education in the University of Maastricht is
      case oriented, whereas the emphasis in ethics teaching in the Catholic University
      of Nijmegen is focused on the methods of ethics and moral reasoning. The general
      objectives, format and evaluation are discussed. Both programmes assume that in
      clinical decision-making normative and technical issues are intertwined; if a
      normative dimension is intrinsic to medical practice itself, students should
      learn during clinical training how to explicate and evaluate the moral quandaries
      of their profession. The positive characteristics of the Maastricht programme
      (student-centred approach, relevant cases, team-teaching of ethicist and
      clinician), if combined with those of the Nijmegen programme (a coherent
      theoretical framework and method for case analysis and interpretation), would
      create a new, powerful model for clinical ethics teaching. In a recent report
      such a model is advocated for all Dutch medical schools.

PMID- 7623684
TI  - Animals for teaching purposes: medical students' attitude.
AB  - Animal rights movements have increased the scope and intensity of their
      activities over the past decade. While it is generally assumed that doctors and
      other members of the health care professions favour the use of animals for
      science, few data are available. Student protests in various medical schools
      against use of animals in teaching laboratories indicated further need for
      objective data. A questionnaire about attitudes to the use of animals for
      teaching purposes was distributed to all the medical students at the Ben-Gurion
      University of the Negev, present during classes on a given day. All students
      present (200) returned the questionnaire (70% of the student body). Also queried
      were attitudes towards related subjects. A high percentage of medical students
      surveyed had significant reservations about animal experimentation for teaching
      purposes and about the preferential priority for human life over that of animals.
      These attitudes, if confirmed, have serious implications for educators both in
      the health fields and otherwise.

PMID- 7623685
TI  - Medical students' contribution to the development of a smoke-free hospital policy
      in a university medical centre: a relevant learning experience.
AB  - In a research methodology course, second-year medical students conducted a survey
      on 'Enforcing a Smoking Ban in the Soroka Medical Center: a Survey of Hospital
      Employees on Facilitating Factors and Obstacles'. They defined the study
      objectives and design, developed the study instrument, carried out the survey,
      coded and entered the data into mainframe computers, analysed the computer
      output, and prepared oral and written reports. The aims of the project were
      twofold: to survey employees' attitudes to a hospital smoking ban and to train
      medical students in the planning and conduct of a research project on public
      health or preventive medicine. Twelve students conducted a cross-sectional survey
      of 208 hospital employees (10% of the hospital staff). Employees were surveyed
      regarding smoking status, interest in quitting smoking, knowledge of the law
      banning smoking in public places, knowledge of the health effects of passive
      smoking, attitudes towards a hospital smoking ban and potential obstacles to its
      implementation. The students rated the course as excellent. They gained important
      research skills, as well as practical medical and public health experience
      through active participation in the design and execution of a study project with
      public health implications. At the first meeting of the hospital committee
      appointed to enforce a smoke-free hospital, the students' findings were reported
      in full, and their recommendations have guided policy decisions.

PMID- 7623686
TI  - Teaching public health: an innovative method using computer-based project work.
AB  - Restructuring of training in public health in the Hungarian medical schools is
      being undertaken in the context of a major European Union TEMPUS Joint European
      Project. Under the aegis of this project a common core curriculum of public
      health has been developed. As part of the implementation of the curriculum, new
      approaches to learning are being explored that should enable students to
      appreciate the nature and magnitude of the major challenges to public health in
      Hungary and promote the development of their analytic, interpretative and
      presentational skills. One of the approaches is based on the individual
      preparation of reports on important public health issues, making use of secondary
      data from electronic databases (WHO HFA/PC and OECD Health Data) and traditional
      printed sources (annuals). This method called 'computer-based project work' was
      introduced in Debrecen in 1992-1993 with a secondary objective to develop basic
      computing skills. The initial experiences of introducing computer-based project
      work to the curriculum have been positive. This paper describes a practical
      example of the implementation of innovative approaches to teaching in a highly
      traditional setting in Central Europe, and one that provides ideas and
      encouragement to those facing similar problems in the countries of Central and
      Eastern Europe and the former Soviet Union.

PMID- 7623687
TI  - Principles of clinical medicine: an interdisciplinary integrated 2-year
      longitudinal course.
AB  - In keeping with the Report of the Panel on the General Professional Education of
      the Physician (Association of American Medical Colleges 1984), Oregon Health
      Sciences University (OHSU) School of Medicine is in the midst of revising its
      curriculum. After a 4-year process, the Curriculum Committee mandated development
      of the Principles of Clinical Medicine course, a 2-year longitudinal course
      integrating input from both basic and clinical science departments. We describe
      the steps leading to the course's implementation, its administrative and
      organizational structure, the evaluation of student performance, teacher
      training, course curriculum, and the use of interdisciplinary teaching. This
      course embodies many of the changes called for in the AAMC Report and serves as a
      model for interdisciplinary education.

PMID- 7623688
TI  - Role of ambulatory care for student-patient interaction: the EPITOME model.
AB  - In undergraduate medical education, a shift away from in-patient teaching towards
      greater use of the ambulatory care setting is occurring. This paper looks at what
      effect this change in emphasis might have on students' clinical competence. A log
      book approach was used to study final-year orthopaedic students' opportunities to
      interact with patients in the wards and out-patient clinics at the University of
      Dundee Medical School. Students perceived that similar opportunities to interact
      with patients to develop and improve their clinical skills were provided by both
      settings. The study showed that much greater use could be made of both settings
      for clinical skills teaching. While students were not enthusiastic about the log
      book approach, it stimulated their thinking. It is concluded that student
      opportunities to develop clinical skills will not be adversely affected by the
      trend towards ambulatory care teaching. There should be more clinical teaching in
      the out-patient setting.

PMID- 7623689
TI  - Structured packs for independent learning in the community.
AB  - A range of structured learning packs (SLIPs) has been developed for third-year
      medical students undertaking a community medicine firm at King's College School
      of Medicine and Dentistry (KCSMD). The aim of the packs is to provide materials
      for independent learning by students to complement teaching by general practice
      tutors. An approach to the development of this method of learning is described. A
      tutor working alongside students designed, tested and revised exercises that were
      developed into learning packs. Tutors who piloted the packs found that they
      offered flexibility and versatility in a general practice setting. The active
      learning exercises were enjoyed by students, who particularly valued tasks that
      fulfilled a genuine practice need. The packs allowed tutors and students to use
      their contact time more effectively by promoting discussion of concepts and
      issues rather than basic clinical information. A formal evaluation programme is
      planned with the aim of extending use of the packs onto other clinical medical
      firms.

PMID- 7623690
TI  - Community-based medical education: feasibility and cost.
AB  - The General Medical Council has issued a call for an increase in community-based
      medical education, and many medical schools are enhancing the community component
      of their curricula. This paper uses the experience of a community-based junior
      medical firm to explore the potential costs, and highlight some of the unresolved
      problems, which a major transfer of education to the community might engender.
      Community-based medical education is not a cheap option. The cost of this
      programme for the academic year 1992-93 was 266,494 pounds, or 60 pounds per
      student session. This compares with the Service Increment for Teaching and
      Research (SIFTR) provision of 41,140 pounds per student per annum, or (excluding
      the 25% of SIFTR which is supposed to cover research costs), 64 pounds per
      student session. There are a number of possible ways of funding community-based
      education, including a diversion of SIFTR toward departments of primary health
      care. As this would have serious implications for the financial viability of some
      medical schools, an urgent discussion about the future funding of medical
      education is required.

PMID- 7623691
TI  - Long-term community-based attachments: the Cambridge course.
AB  - This paper reports on the establishment of the Cambridge Community-based Clinical
      Course and places on record details of the organization, goals and teaching
      arrangements of the course. It also identifies the main questions which are being
      addressed in the course and which must be answered before it will be clear
      whether such attachments are generally viable.

PMID- 7623692
TI  - Obstetric and neonatal competence of medical students.
AB  - During 1991-1992 a confidential questionnaire was administered to a sample of
      United Kingdom medical students to determine if undergraduate education improved
      students' perceived competence at eight practical procedures. Of 2521 students
      given questionnaires, 1483 (58.8%) replied; 948 (65.5%) had had some obstetric
      and 866 (60.8%) some neonatal education. Such education did improve students'
      perceived competence (P < 0.001) on self-assessed Likert scales, but most still
      believe themselves not to be competent when they have completed their obstetric
      and neonatal education. Regression models were able to explain much (38.7-65.1%)
      of the variability in perceived competence at obstetric procedures: obstetric
      education, performing practical procedures, and witnessing deliveries in a
      general practitioner unit were all associated with higher competence; but less
      (4.8-20.8%) of the variability in perceived neonatal competence. It is suggested
      that undergraduate experience should be congruent with the aims and objectives of
      obstetric and neonatal education, and that these need to be reviewed in the light
      of the recent General Medical Council proposed changes to medical education.

PMID- 7623693
TI  - Audit: trainers' and trainees' attitudes and experiences.
AB  - Little is known about the audit activity taking place among general practitioners
      as part of their vocational training. All 155 trainers and their trainees in the
      West of Scotland were asked about their attitudes to and their experiences of
      audit. Two hundred and thirty-five replies were received from 310 questionnaires
      sent, giving an 85% response from trainers and 67% from trainees. Both trainers
      and trainees had positive attitudes to audit with regard to its use: for
      assessing work (87% of trainers, 97% trainees); as an appropriate use of
      resources (92% of trainers, 78% of trainees); as an appropriate use of time (91%
      trainers, 76% trainees); in improving patient care (96% of trainers, 76% of
      trainees). Most trainers (90%) and 52% of trainees had started collecting data
      with a view to starting an audit, 56% of trainers and 23% of trainees had
      personally set a standard and 54% of trainers but only 12% of trainees had
      completed a cycle of audit. Despite very positive attitudes to audit there is a
      problem completing a cycle of audit, particularly among trainees. They will thus
      be denied the benefit of negotiating and evaluating change as part of their
      training, skills which will be necessary to ensure a lifelong awareness of the
      quality of care they are providing.

PMID- 7623694
TI  - Patients' assessment of trainee general practitioners.
AB  - To determine patients' attitudes to their involvement in assessment of trainee
      and qualified general practitioners, and their preferences for the methods
      currently used, a closed-question questionnaire was distributed for self-
      completion to 300 patients, randomly selected from the waiting areas of three
      training practices and one non-training practice in the West of Scotland. Most
      (208) of the 266 patients who responded were comfortable with the idea of being
      involved in the training and assessment of general practitioners. Patients have
      clear views and preferences, and it would be wrong to disregard them.

PMID- 7623695
TI  - Audit and summative assessment: two years' pilot experience.
AB  - An audit project has been submitted by all trainees in the West of Scotland since
      1992 as part of a pilot process for summative assessment. The impact of 2
      consecutive years of audit was assessed on 117 trainees in May 1994. A response
      rate of 89% was achieved. For 82 trainees (79%) this was their first practical
      experience of audit and as a result of it 85% felt more confident in introducing
      change to their next practice. Protected time was still a problem for the
      majority (53%) and one-third wanted more help from their trainer. Thirty trainees
      (29%) had attended four or fewer formal practice meetings in their 10 months of
      training, with 10% never having attended one. The previous trainee's audit
      project was rarely or never discussed with 70 trainees (87%) and only 12 trainees
      were evaluating changes recommended. An audit project as part of summative
      assessment may be encouraging trainees to think about change after they leave
      their training practices. Few, however, are evaluating change and protected time
      and support are still required. The marking of the summative assessment audit
      project may need to address this.

PMID- 7623696
TI  - Comparison of teachers at a 'traditional' and an 'innovative' medical school.
AB  - A 50% random sample (n = 186) of teaching staff at a 'traditional' medical school
      and all staff (n = 205) at an 'innovative' school were surveyed on their
      attitudes to teaching and teacher training. Response rates were 80% and 93%
      respectively. Staff at both institutions were predominantly men, highly
      experienced and active as teachers. Though only a minority had undergone recent
      teacher training, some 95% rated their teaching as 'average' or 'above average'.
      High levels of enthusiasm for teaching were detected in both schools. Staff at
      the 'innovative' school were more positive about the rewards for teaching. There
      was a common perception that formal training would improve the quality of
      teaching, though a third would not wish to participate. When developing
      strategies to enhance the quality of medical teaching, it is important to
      appreciate the existing attitudes of teachers. This survey indicates that
      inflated views of their own teaching ability, a perceived lack of reward for
      teaching, and ambivalence towards formal teacher training are three problem areas
      which need to be considered.

PMID- 7623697
TI  - Affirmative action and academic support: African medical students at the
      University of Cape Town.
AB  - As a result of the policy of apartheid, the University of Cape Town Medical
      School was prevented from admitting black African students by the South African
      Government until 1986. A further feature of this policy was to impose an inferior
      primary and secondary school education in African pupils, so that, in general,
      African school-leavers are underprepared for tertiary education. Admission to
      medical school is highly competitive and African school-leavers are unable to
      compete effectively with their counterparts from the other racial groups.
      Therefore, from 1986 to 1990 inclusive, an affirmative action admissions policy
      was followed that allowed the most successful African matriculants, whether
      competitive or not, to enter the Medical School and follow the regular course of
      study. This process failed in that an inadequate number of students gained
      admission to the MBChB programme and their academic progress was unsatisfactory.
      Since 1991, an affirmative action policy incorporating both academic support and
      mentor programmes has been followed by the Faculty of Medicine. This system has
      led to a substantial increase in the number of African students entering the
      first year of study and it is planned that up to 40% of all matriculants entering
      the MBChB programme in 1995 will be via this system. The academic load is
      reduced, and the results the students obtain at university have markedly
      improved, with 86% of students achieving the academic goals that they are set.
      The comparison between these two systems emphasizes the need to provide both
      academic and social support as well as flexibility in the curriculum if and
      affirmative action policy is to succeed.

PMID- 7623698
TI  - Stress and vulnerability in medical students.
AB  - One hundred and forty Hong Kong Chinese students were surveyed early in the
      second year of their medical education (year 2), and compared with 138 students
      surveyed prior to beginning their first year of medical school and with 74 non
      medical university students in their second year. In year 2 students, distress as
      reflected in their scores on anxiety and depression self-report scales was high,
      and these students reported greater utilization of health professional services
      as compared with the other two groups. In year 2 students, concerns related to
      the medical school environment and curriculum, and whether one has the endurance
      and ability to be successful were significant correlates with depression and
      anxiety. Loss of opportunity to maintain social and recreational sources of
      gratification correlated with anxiety. There was no difference between the sexes
      with regard to the development of anxiety and depression symptoms. Academically
      less successful students reported somewhat higher levels of depressive ideation
      and symptomatology. Trait anxiety correlated with the development of distress,
      while optimism protected against the development of distress. Active coping
      styles and positive reinterpretation as a coping strategy correlated negatively
      with distress, while wishful thinking correlated positively with distress. These
      findings emphasize the need for greater attention to the psychological well-being
      of doctors-in-training, in Hong Kong as in the Western world. These findings
      should be further explored in longitudinal studies, and may be helpful in
      designing intervention and support programmes for vulnerable students.

PMID- 7623699
TI  - Medical students in a time of HIV: education and the duty to treat.
AB  - This article concerns medical education about the ethics of professional duties
      and treatment of HIV-infected patients. The issue at hand is not whether medical
      students have a duty to treat HIV-infected patients, since it is a matter of
      consensus that they do. Medical schools have reasserted that risks are inherent
      in medicine, and that medical school admission should be based on the willingness
      to accept some risks, in addition to intelligence and personal skills. Those who
      wish to avoid risks are free to enter other professions. While it is imperative
      to assert a duty to treat, this requires thoughtful explanation to match the
      understandably high anxiety levels of many medical students.

PMID- 7623700
TI  - MEDLINE training for medical students integrated into the clinical curriculum.
AB  - This study was initiated in response to the availabilty of unlimited access to
      MEDLINE via the PaperChase interface at the host institution. The goal of the
      study was to analyse the usage of MEDLINE by medical students during their third
      year clinical clerkship in paediatrics. This was achieved by first giving them a
      formal demonstration of MEDLINE and then longitudinally administering a
      structured questionnaire at several points during their paediatric clerkship.
      Since medical students were required to write a thesis for this clerkship, which
      included an analysis of the primary literature, there was an identified need for
      using the system. This study analyses the students' perceptions and searching
      activities after formal training and upon having unlimited access to MEDLINE.

PMID- 7623701
TI  - Comparison of training techniques using a patient-centered approach to smoking
      cessation.
AB  - This study compared the use of 2 1/2-hour multimedia workshop with distribution
      of an algorithm on the ability of fourth-year medical students to present a stop
      smoking plan to a simulated patient. Results showed that students who
      participated in the workshop performed statistically significantly better on the
      skill areas of providing information, eliciting and responding to feeling and on
      content areas of past experience with quitting, resources available for change
      and negotiating a plan. There were no significant differences in the skill area
      of eliciting information and the content areas of motivation to stop smoking,
      factors that inhibit change and problems affecting the plan. Neither of the
      groups performed very well. The highest number of available points obtained by
      both groups was in eliciting information (53% in the algorithm group and 64% in
      the formal training group); however, most of the values were in the range of 10%
      25% of possible points. Suggested reasons for the low values may be due to the
      specific items rated, the teaching methods or the time needed to assimilate new
      skills.

PMID- 7623702
TI  - Competence-based summative assessment of a student-directed course: involvement
      of key stakeholders.
AB  - The 5-week module in general practice for final-year students at the University
      of Sheffield is based on practice attachments and student-directed learning in
      small groups. This paper describes how the summative assessment process of the
      module was revised to incorporate the notion of competence-based assessment, and
      how general practitioner tutors, departmental tutors and students were involved
      in this revision. The question 'What are students expected to know and be able to
      do by the end of the module?' was answered in terms of a statement of the key
      purpose of the module and a list of intended learning outcomes. The question 'How
      can we find out if students have achieved these outcomes?' was addressed by
      developing check-lists of criteria for observed behaviours and for the written
      products of students' actions.

PMID- 7623703
TI  - A new method of assessment of clinical teaching: ROC analysis.
AB  - Twenty-five clinical dental students with varying clinical experience were
      presented with case records consisting of a clinical history and a panoramic
      radiograph for 25 patients with bilateral lower third molars ('wisdom teeth').
      The students were asked to indicate how certain they were that each lower third
      molar tooth needed removal using a 6-point rating scale. Immediately following
      the task, the students were presented with information on the indications for
      removal of lower third molars in the form of a lecture by a senior academic
      clinical teacher. One week later the students were asked to repeat the rating
      study, under the same conditions as before, using a further 25 clinical cases.
      Receiver operating characteristics (ROC) analysis, which provides a graphical and
      quantitative assessment of a group of observers' ability to detect need for
      treatment, was utilized to examine differences between junior and senior students
      and between the matched pre-training and post-training experiments. The ability
      of junior students to assign lower third molars for surgery was statistically no
      better than random selection of cases. Formal clinical teaching significantly
      improved this group's performance, but had no effect on the performance of senior
      students. Senior students were significantly better able correctly to assign
      lower third molars for surgical intervention than junior students. Therefore this
      study shows that clinical experience has a significantly greater influence on
      treatment-planning ability than formal teaching. ROC analysis is a useful tool
      for assessing the effectiveness of methods of undergraduate training.

PMID- 7623704
TI  - Teaching immediate cardiac care to general practitioners: a faculty-based
      approach.
AB  - This paper describes the development, piloting and delivery of an immediate care
      cardiac course (ICCC) to Irish general practitioners. The course utilizes the
      continuing medical education network of the Irish College of General
      Practitioners. This has made the course locally accessible even for remote
      practitioners and has facilitated rapid dissemination. In its first year, 167 GPs
      (8% of the total number of Irish GPs) have completed the course. Participant
      feedback has been positive, especially regarding the small group- and skills
      based components. The introduction of more formal assessment procedures is now
      being undertaken. We believe this model to be a possible template for the
      introduction of other skills courses both in Ireland and abroad.

PMID- 7623705
TI  - Educational assessment of general practice experience for psychiatric trainees.
AB  - Eighteen psychiatric trainees spent 6 months each as general practice trainees.
      The educational impact of the experience was assessed by a self-assessment
      questionnaire, a semi-structured interview and a videotaped interview with a
      psychiatric patient. Each assessment was conducted at a baseline and after 12
      months. A control group of 14 trainees was recruited from the same rotation. On
      the self-assessment questionnaire, the study registrars rated their abilities to
      solve general medical problems significantly improved compared to controls. They
      had also acquired greater understanding of the limitation of their knowledge and
      their legal responsibilities towards their patients. The semi-structured
      interview failed to distinguish between the two groups. Videotapes for rating at
      baseline and follow-up were available for only 17 of the trainees. Assessment of
      the tapes used the Maguire Scale and the Interview Behaviour Scale. Neither scale
      demonstrated any intervention effect. The interviews were all characterized by a
      preponderance of 'closed psychological' and 'checking-out' questions. It appears
      that psychiatric trainees' interviewing styles had not been influenced by the
      experience. This study suggests that psychiatric trainees gain greater confidence
      in their role as a doctor and greater understanding of the scope and nature of
      general practice by such an attachment. It is unclear whether or not
      supplementary interviewing skills had been acquired which were not utilized in
      the taped interview, which conforms very much to traditional psychiatric
      examination behaviour. Trainees were reassured that they had increased their
      knowledge without losing any of their specific professional skills.

PMID- 7623706
TI  - Child and adolescent psychiatry placement in specialist psychiatric training: a
      regional study.
AB  - Before beginning higher professional training in one of the subspecialties, all
      psychiatry trainees must complete a general professional psychiatric training. At
      this stage, some but not all will undertake a clinical placement in child and
      adolescent psychiatry. Fifty-seven trainees who had completed one of the 15 child
      and adolescent psychiatry placements in a Regional Health Authority, took part in
      a semi-structured telephone interview. The trainees were asked to compare the
      child and adolescent psychiatry placement with a general adult psychiatry
      placement with respect to the training received in a number of areas. These areas
      were considered to be important to psychiatrists of all future subspecialties and
      included: assessment, communication, psychological interventions and
      psychological theories. In addition, subjects were asked about their general
      professional training as a whole and the role that child and adolescent
      psychiatry placements should play. The interview included quantitative and
      qualitative components. The findings suggest that child and adolescent psychiatry
      placements can make a significant contribution to a number of important areas of
      general professional development and that there would be considerable support for
      strengthening the role of such placements in psychiatry training.

PMID- 7623708
TI  - The regional conference for Africa.

PMID- 7623707
TI  - Medical audit and medical education.

PMID- 7623709
TI  - Australian medical education in a time of change: a view from the University of
      Sydney.
AB  - In 1991, vigorous debate was regenerated in the Faculty of Medicine at the
      University of Sydney about the desirability of changing the traditional 6-year
      undergraduate medical programme to a 4-year, graduate model. Similar discussion
      occurred at the same time largely independently in two other Australian medical
      schools (at Flinders University and the University of Queensland). After a year
      of active investigation and consideration, all three made the decision to
      proceed. Although the specific reasons driving each institution differed
      somewhat, some concerns were common to all three. I here review the history of
      the process of change, the strategies used to encourage discussion and the major
      issues for the Medical Faculty at the University of Sydney.

PMID- 7623710
TI  - Personality, lifestyles, alcohol and drug consumption in a sample of British
      medical students.
AB  - Personality characteristics and lifestyle variables were assessed in two cohorts
      of second-year medical students at the University of Newcastle upon Tyne, UK as
      part of a psychopharmacology 'teach-in' in 1993 and 1994. The pooled sample
      included 186 students: 77 men, 109 women, mean age 20.4 +/- 1.8 years. Measures
      included the Eysenck Personality Questionnaire, the Hospital Anxiety Depression
      Scale, and a questionnaire concerning consumption of alcohol, tobacco, cannabis
      and other illicit drugs, and physical exercise. The results were compared, where
      possible, with a similar survey in Newcastle upon Tyne medical students in 1983
      and 1984. Personality variables, prevalence of cigarette smoking, levels of
      caffeine consumption and participation in sports had not changed significantly
      over the decade. There appeared to be a modest overall increase in alcohol
      consumption and in the 1993 and 1994 cohorts of students, 25.5% of those who
      drank alcohol exceeded recommended low risk levels (comparable data not available
      for 1983 and 1984). Reported use of cannabis and other illicit drugs had more
      than doubled, and in the present survey 49.2% of students recorded using cannabis
      and 22% had tried other illicit drugs. Corresponding figures for 1983 and 1984
      were 20.9% for cannabis and 3.3% for other illicit drugs. Anxiety levels were not
      measured in 1983 and 1984 but in the present survey 39.3% of the students had
      anxiety ratings within the clinically significant range. The high levels of
      alcohol consumption and illicit drug use, and the high anxiety ratings, in this
      sample of medical students are a cause for concern.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7623711
TI  - Students' perception of good and bad teaching: report of a critical incident
      study.
AB  - Evaluation of teaching by the use of questionnaires to students is now
      commonplace. If it is to be useful the data obtained must be reliable and valid.
      One criterion of reliability is the response rate, and a low response rate may
      indicate low validity, i.e. that the questions asked do not reflect the students'
      real concerns. In order to inform questionnaire design a critical incident study
      was undertaken. A 20% random sample of students in each of the 5 years of the
      course were asked to describe one piece of good teaching and one piece of bad
      teaching, and say why they were good or bad. There was a 65% response rate, and
      replies were independently categorized by three people. The factors identified
      fell into three 'domains': interpersonal behaviour of teachers; planning and
      preparation; and the ability to run the session well. There was no evidence that
      teaching which 'played to the gallery' or was very examination-oriented would
      earn high ratings from students.

PMID- 7623712
TI  - Initial responses of first-year medical students to problem-based learning in a
      behavioural science course: role of language background and course content.
AB  - A trial of problem-based learning (PBL) was conducted with first-year
      undergraduate medical students who had no background knowledge of behavioural
      science and who included a substantial proportion with a first language other
      than English. Responses to standardized and open-ended evaluation questions
      showed greater variability and there was no clear preference for PBL over
      traditional methods. Students found the PBL exercise time-consuming and felt they
      needed more guidance. Feedback from clinicians and working in groups were seen as
      positive aspects of the exercise. Students with a first language other than
      English reported that language, but not cultural background, was an impediment to
      effective participation. It is recommended that this group of students be offered
      extra support for PBL in a subject-based setting, and that all students would
      benefit from a formal induction session.

PMID- 7623713
TI  - Teaching sociology of medicine: the group process.
AB  - As a part of any curriculum reorganization, new instructional methods are also
      tested. When the University of Turku sociology of medicine course was found to
      need renovation, its goals and objectives, content and instructional methods were
      closely examined and modified, in order to strengthen institutional and
      multiprofessional relations and reinforce sociocultural issues in doctors'
      competence with the patient. This paper discuss this change, emphasizing teaching
      and learning methodology.

PMID- 7623714
TI  - Assessing personal process learning in a health promotion module for medical
      students.
AB  - This paper describes the development and evaluation of an assessment method for
      personal process learning in a student-centred health promotion module. Personal
      process learning refers to students' awareness and understanding of their
      learning about personal values and attitudes, their skills for planning change,
      and their communication skills. The assessment forms part of the professional
      examination in public health. The paper documents and critically reviews the
      assessment method in the light of student feedback. The problem of student
      acceptability is highlighted and we describe the adjustments that have been made
      in response to this and how they have been received. It is concluded that medical
      students are open to innovative forms of assessment as long as they perceive them
      to be valid, fair and equitable.

PMID- 7623715
TI  - Is an intercalated BSc degree associated with higher marks in examinations during
      the clinical years?
AB  - Do medical students taking an intercalated BSc degree obtain higher marks during
      their subsequent clinical examination? Fourteen students who did a BSc during the
      academic year 1988-89 were matched, by sex and preclinical grades, with students
      in the year they left, and with students in the year they subsequently joined.
      Marks or grades in 10 subsequent examinations were compared. Seven of 10
      comparisons with the year the BSc students left were to the advantage of the
      intercalated students, and two comparisons were statistically significant. Seven
      of 10 comparisons with the year the BSc students subsequently joined were to the
      advantage of the non-intercalating students, though none reached statistical
      significance. No consistent short-term academic advantages arising from having
      done a BSc could be found. We suggest the study be replicated in other medical
      schools with different course examination structures.

PMID- 7623716
TI  - Development and implementation of an innovative intern training programme.
AB  - The quality of medical education during internship is a cause for concern. This
      paper describes a structured educational programme for interns that was based
      around learning modules, clinical attachments and bedside teaching. The programme
      was incorporated into the term rotation of interns within an Area Health Service,
      and evaluated. Learning modules were timetabled by a Programme Coordinator and
      interns were reminded to attend. Clinical attachments were organized by the
      interns from a list of willing supervisors. Attendance at timetabled learning
      modules averaged 67%, which was greater than the 27% attendance at clinical
      attachments. Both sessions received high ratings for quality and clinical
      relevance. This structured education programme was based upon adult learning
      methods and was both feasible and well received by interns. Intern training
      programmes need to be programmed into the working week to ensure attendance, and
      modified following evaluation by interns. Such programmes should be considered by
      all hospitals to which interns are allocated.

PMID- 7623717
TI  - Clinical competence of interns. Programme Evaluation Committee (PEC).
AB  - A clinical supervisors rating form addressing 13 competencies was used to assess
      the clinical competence of graduates one year after qualification in New South
      Wales (NSW), Australia. Data from 485 interns (97.2%) showed that graduates from
      the problem-based medical school were rated significantly better than their peers
      with respect to their interpersonal relationships, 'reliability' and 'self
      directed learning'. Interns from one of the two traditional NSW medical schools
      had significantly higher ratings on 'teaching', 'diagnostic skills' and
      'understanding of basic mechanisms'. Graduates from international medical schools
      performed worse than their peers on all competencies. These results were adjusted
      for age and gender. Additionally, women graduates and younger interns tended to
      have better ratings. Junior doctors have differing educational and other
      background experiences and their performance should be monitored.

PMID- 7623718
TI  - How do clinicians learn to request permission for autopsies?
AB  - A postal survey of 434 clinicians at four local hospitals was undertaken in order
      to identify the methods by which clinicians learn how to request permission for
      hospital autopsies and to assess the preferred techniques and timing of relevant
      communication skills training. The majority of 128 responding clinicians had
      learnt through personal experience with some assistance from senior colleagues
      and peers. Few clinicians appeared to have learnt through formal training. The
      preferred methods for the provision of communication skills training were
      training in small groups (such as seminars or tutorials) and observation of
      clinicians at work. The most desirable time for the provision of this training
      was considered to be between the beginning of the final undergraduate year and
      the end of the pre-registration house officer year. The communication skills
      training provided within medical education is in need of improvement. More
      emphasis should be given to clinical-task- or situation-specific applications
      such as requesting permission for autopsies.

PMID- 7623719
TI  - Trans-European medical education: experience of the Faculty of Medicine of
      Oviedo.
AB  - The European Community has played a key role in organizing student mobility
      programmes and in emphasizing the need for a European medical culture. The need
      for a common core of medical principles and efforts to strengthen inter-European
      cooperation nurture the philosophy of these exchanges. The Faculty of Medicine of
      Oviedo has been working on student mobility programmes for the last 7 years. As a
      result of this activity, about four hundred medical students have participated in
      various exchanges. This experience is highly positive both for the students and
      for the institutions taking part in it. The students have the chance to become
      acquainted with a different country, language, culture and medical training
      system. Meanwhile, the institutions benefit from their students' experience as
      well as having the opportunity of starting further cooperative programmes.

PMID- 7623720
TI  - Child health surveillance: development of a multicentre course and its
      evaluation.
AB  - With increasing numbers of general practitioners wishing to provide child health
      surveillance during the 1980s and the expected further increase with the 1990
      General Practice Contract, a course in child health surveillance was developed.
      The content of the course was determined by a needs assessment of Welsh general
      practitioners in combination with the expectations of paediatricians already
      involved in educating doctors in community child health. A multicentre course
      with prepared materials was developed. Teaching methods reflected adult learning
      needs, included practical clinical competencies and was centred in small groups
      each led by local tutors. The course was held annually on three occasions, with
      220 participants in total. The materials and teaching methods were highly
      acceptable to the participants, and evaluation demonstrated a significant
      increase in knowledge and confidence. All participants reached the required
      clinical competence, six after further teaching. The content, teaching methods,
      and evaluation methods were altered in the light of feedback, resulting in a
      'stand alone' course with built-in evaluation, which is now being provided by
      local tutors. This study has demonstrated the feasibility of providing a course
      for large numbers of doctors, using predominantly small-group teaching and
      discussion with local tutors. We are grateful to all the participants and
      especially the tutors.

PMID- 7623721
TI  - Assessment of competence in technical clinical skills of general practitioners.
AB  - Technical clinical procedures constitute an important part of the work of general
      practitioners. Assessment of competence in the relevant skills is important from
      the perspective of quality assurance. In this study, the psychometric
      characteristics of three different methods for assessment of competence in
      technical clinical skills in general practice were evaluated. A performance-based
      test (8 stations), a written knowledge test of skills (125 items) and a self
      assessment questionnaire (41 items) on technical clinical skills were
      administered to 49 GPs and 47 trainees in general practice. The mean scores on
      the performance-based test and the written knowledge test of skills showed no
      substantial differences between GPs and trainees, whereas the GPs scored higher
      on the self-assessment questionnaire. While the correlation of the score on the
      knowledge test of skills with the score on the performance-based test was
      moderately high, the score on the self-assessment questionnaire showed a rather
      low correlation with the performance-based test. Although performance-based
      testing is obviously the best method to assess proficiency in hands-on skills, a
      written test can serve as a reasonable alternative, particularly for screening
      and research purposes.

PMID- 7623722
TI  - Should all medical students do research during their studies?

PMID- 7623723
TI  - A novel extension of problem-based learning: problem-based lecture presentation
      by students.

PMID- 7623724
TI  - Health-related behaviors of survivors of childhood cancer.
AB  - The health-related beliefs and behaviors of long-term survivors of childhood
      cancer are important because of vulnerability to adverse late effects from their
      primary malignancy and its therapy. A health behavior survey was completed by 110
      parents of long-term survivors ranging in age from 11-17 years, and by 40 adult
      long-term survivors of childhood cancer ranging in age from 18-29 years. The
      survey included questions on the former patient's frequency of alcohol and
      tobacco use, as well as diet, exercise, sleep, dental, and seatbelt habits. The
      reported prevalence of tobacco and alcohol use was less than 10% among those less
      than 18 years old. Among the adults, tobacco (17.5%) and alcohol (72.5%) use was
      greater, but problem drinking was infrequently reported. In order to assess their
      perceived vulnerability, we asked the parents and the young adult patients to
      rate the strength of their belief that it is more important for the patient to
      keep healthy compared to most other children or young adults. Contrary to our
      expectation, demographic factors such as the patient's gender, socioeconomic
      level, or time elapsed since completion of therapy exerted minimal influence on
      their responses. Over 80% of parents and 60% of young adult survivors believed
      that it was more important for the former patient to remain healthy compared to
      most other people. However, this shared belief in increased vulnerability was
      inconsistently expressed in the patient's health behaviors. These results suggest
      that specific changes are needed in the health assessment and education of long
      term survivors of childhood cancer.

PMID- 7623726
TI  - Fractionated total-body irradiation preceding high-dose cytosine arabinoside as a
      preparative regimen for bone marrow transplantation in children with acute
      leukemia.
AB  - Twenty children with acute leukemia between 3 and 19 years of age underwent
      allogeneic bone marrow transplantation from HLA-matched sibling donors after
      conditioning with total-body irradiation (1,200 cGy in six fractions of 200 cGy
      twice daily for 3 days) and high dose cytosine arabinoside (3 g/m2 given every 12
      hours for 12 doses). Three patients died with acute toxicity. Six patients
      developed grade II acute graft versus host disease. With a median follow-up of 68
      months (range 26-96 months), thirteen children (65%) are alive and in remission
      with Karnofsky scores of 90-100%. A patient with AML in resistant relapse went
      into remission but relapsed and died 5 months post-transplantation. Three other
      patients relapsed, 8, 12, and 16 months post BMT. Our results suggest that this
      conditioning regimen is associated with high but manageable acute toxicity and
      may be highly effective in controlling leukemia resistant to conventional
      chemotherapy.

PMID- 7623725
TI  - Prospective randomised trial of chemotherapy given before radiotherapy in
      childhood medulloblastoma. International Society of Paediatric Oncology (SIOP)
      and the (German) Society of Paediatric Oncology (GPO): SIOP II.
AB  - In a multicentre randomised clinical trial 364 children with biopsy proven
      medulloblastoma were randomly assigned to receive or not pre-radiotherapy
      chemotherapy. Children with total or subtotal removal of the tumour, no evidence
      of invasive brain stem involvement, and no evidence of metastatic disease either
      within or without the cranium were designated "low risk", those with gross
      residual tumour, evidence of invasive brain stem involvement or metastases in the
      central nervous system were designated "high risk". All children were prescribed
      55 Gy to the tumour bearing area. "Low risk" children could be randomised to
      "standard" radiotherapy 35 Gy to the craniospinal axis or "reduced" dose 25 Gy to
      the craniospinal axis. Chemotherapy consisted of vincristine, procarbazine, and
      methotrexate given in a 6-week module before radio-therapy, and for "high risk"
      children, vincristine and CCNU given after radiotherapy. No benefit for the
      receipt of pre-radiotherapy chemotherapy could be demonstrated for any group. In
      addition, a negative interaction was observed between the receipt of the
      chemotherapy and reduced dose radio-therapy with a particularly poor outcome
      being observed in this group of children.

PMID- 7623727
TI  - Cardiac troponin T and creatine kinase MB mass concentrations in children
      receiving anthracycline chemotherapy.
AB  - Anthracyclines (doxorubicin, daunorubicin, and derivatives) are among the most
      effective antineoplastic drugs for pediatric cancer with dose-limiting acute and
      long-term cardiotoxicity. The exact mechanism of the development of
      cardiomyopathy is still not clear. Anthracyclines may induce subclinical acute
      myocardial injury leading to lysis of a limited number of myocytes.
      Alternatively, myocytes may experience a transient loss of cytoplasmic membrane
      integrity. Both conditions may lead to a transient efflux of small amounts of
      cytoplasmic enzymes and other proteins specific to the heart muscle fibers. To
      test these hypotheses we assayed plasma creatine kinase (CK) MB mass and cardiac
      specific troponin T (TnT). CKMB may be released even in case of reversible cell
      membrane injury, while prolonged elevation of TnT is the most sensitive and
      specific marker of limited myocardial necrosis. Thirty-five anthracycline
      containing chemotherapy courses in 22 children with cancer were analyzed. CKMB
      mass and TnT concentrations were within the normal range in all children before
      anthracycline therapy. Within 72 hours from anthracycline therapy no increment of
      one of these two marker proteins was detected (ANOVA for repeated measures, P =
      0.94 [TnT] and 0.25 [CKMB]). We conclude that only minimal if any acute necroses
      of cardiac myocytes occur after anthracycline therapy. Even membrane integrity
      appears to be maintained within the first 3 days after anthracycline therapy, in
      the absence of electrocardiographic or echocardiographic signs of acute
      cardiotoxicity.

PMID- 7623728
TI  - Cyclophosphamide in combination with sargramostim for treatment of recurrent
      medulloblastoma.
AB  - Thirteen patients with recurrent medulloblastoma were treated with
      cyclophosphamide in association with Sargramostim. Cyclophosphamide was given at
      doses ranging between 1.0-2.5 g/m2 daily for two doses. Sargramostim was given at
      a fixed dose of 250 micrograms/m2 subcutaneously twice a day beginning 24 hours
      after the second cyclophosphamide dose and continuing through the leukocyte nadir
      until the ANC was more than 1,000 cells/microliters for two consecutive days. A
      total of 33 courses were given with toxicity consisting of grade 4 neutropenia in
      all courses and grade 3-4 thrombocytopenia in 10 of 13 patients. There were no
      deaths related to infection or bleeding. Four patients were taken off study
      because of prolonged myelosuppression. Three of these patients were at the 2.5
      g/m2 level, and of these three, two developed lung toxicity (grades 2 and 4,
      respectively). One patient developed an allergic reaction following the first
      injection of Sargramostim and was also taken off study. Of 10 evaluable patients,
      there were 9 PR and 1 SD. We conclude that cyclophosphamide at a dose of 2.0
      g/m2/day x 2 days q 4 weeks in association with Sargramostim demonstrates marked
      activity with acceptable toxicity in patients with recurrent medulloblastoma.

PMID- 7623729
TI  - Childhood acute lymphoblastic leukemia in India: an approach to management in a
      three-tier society.
AB  - Within a population of 882 million, six thousand children will develop acute
      lymphoblastic leukemia each year in India. These children come from three socio
      economic backgrounds: Profile I (70%) being extremely poor who cannot afford any
      treatment unless it is provided free, Profile II (25%) from the middle class, and
      Profile III (5%) who can afford to have the best possible treatment. Current
      protocols for childhood ALL range from simple low-cost regimes like UKALL VIII,
      intermediate intensity regimes like BFM 76/79, and aggressive regimes aimed at
      increasing cure rates in the high risk groups. Since state resources are limited,
      the pediatric oncologist in India has to decide on the appropriate treatment
      protocol for the individual child in each of these profiles. This paper suggests
      an approach to managing childhood ALL in developing countries like India.

PMID- 7623730
TI  - Rapid cytoreduction in childhood leukemic hyperleukocytosis by conservative
      therapy.
AB  - Childhood leukemic hyperleukocytosis poses a serious threat to life because of
      its associated metabolic complications. The present prospective trial utilized
      conservative management of childhood acute lymphoblastic leukemia with
      hyperleukocytosis (total white cell count equal or > 100 x 10(9)/L) by
      intravenous hydration, urinary alkalinization, and allopurinol presenting without
      severe life-threatening complications. The median reduction in WBC count was
      81.51% (range: 66-98.8%) within a median period of 36 hours (range: 12-60 hours)
      following hospitalization. There were no failures or treatment related
      complications. Thus we conclude that in childhood acute lymphoblastic leukemia,
      hyperleukocytosis can be managed safely and effectively with intravenous
      hydration, urinary alkalinization, and allopurinol before starting any specific
      anti-leukemic chemotherapy avoiding risk-associated cranial irradiation,
      leukapheresis, and exchange transfusion.

PMID- 7623731
TI  - Urticarial vasculitis: an autoimmune disorder following therapy for Hodgkin's
      disease.
AB  - Immunological abnormalities have been described in patients with Hodgkin's
      disease, both associated with the malignancy itself and occurring secondary to
      therapy. These abnormalities often manifest as an immunodeficiency state, but can
      also present as immune dysregulation and autoimmune disease. We report two young
      patients with Hodgkin's disease who, following successful therapy, developed
      urticarial vasculitis (UV), a form of cutaneous autoimmune vasculitis. Both
      patients also had systemic symptoms including fever, an elevated erythrocyte
      sedimentation rate and serum copper, and abnormal in vitro studies of lymphocyte
      enumeration and proliferation. Distinguishing UV from recurrent Hodgkin's disease
      was especially difficult in one patient, and was possible only by lymph node
      biopsy. One patient has responded well to immunosuppressive therapy, while the
      other, who has more profound immune dysfunction, has developed a chronic
      autoimmune disorder. UV may thus occur in patients after therapy for Hodgkin's
      disease; we hypothesize that immune dysregulation, either associated with the
      malignancy or resulting from therapy, is important in the pathogenesis of this
      autoimmune process.

PMID- 7623732
TI  - Neurofibromatosis type 1.

PMID- 7623733
TI  - "Childhood ALL and cystic fibrosis--treatment and outcome".

PMID- 7623734
TI  - A new approach for the study of the neurotoxicity of lead.

PMID- 7623735
TI  - Long-term learning deficits and changes in unlearned behaviors following in utero
      exposure to multiple daily doses of cocaine during different exposure periods and
      maternal plasma cocaine concentrations.
AB  - Although the possible behavioral neurotoxic effects of in utero exposure to
      cocaine have been the subject of numerous experiments, only a limited number of
      different types of animal models of cocaine exposure, critical periods, or long
      term effects of such exposures have been investigated. In the present experiment,
      the effects of multiple daily SC exposures to cocaine (20 mg/kg/dose x 5 doses
      per day) were investigated when administered to gravid Sprague-Dawley CD rats on
      embryonic days E7-12 or E13-18 compared to weight-matched, vehicle injected, pair
      fed controls. Effects of exposure were assessed on general development, olfactory
      orientation behavior, early locomotion, startle reactivity, spontaneous motor
      activity, and learning on two different tasks (Morris and Cincinnati water
      mazes). The multiple cocaine dosing regimen produced maternal peak serum
      concentrations of cocaine 3 times higher than that of a single dose
      (approximately 1550 vs. approximately 550 ng/mL). Early-exposed cocaine offspring
      had lower olfactory orientation scores and reduced postweaning rearing and hole
      poke motor activity, whereas late-exposed cocaine offspring had increased
      postweaning locomotor, rearing, and hole-poke activity. On the Morris hidden
      platform maze, the cocaine early-exposed females had longer latencies on
      acquisition than controls. On the Cincinnati multiple-T water maze, the early
      exposed cocaine females and the late-exposed cocaine males had increased errors,
      whereas the early-exposed cocaine males had reduced errors. The effects on
      measures of learning, when taken together, and in light of their being in the
      early-exposed group, suggest that embryonic cocaine exposure may have subtle
      effects on cognition in the offspring as adults. Such effects represent a form of
      neurotoxicity not previously associated with prenatal cocaine exposure.

PMID- 7623736
TI  - Behavioral avoidance of fluoranthene by fathead minnows (Pimephales promelas).
AB  - A monitoring system was used to examine the behavioral response of fathead
      minnows (Pimephales promelas) to plumes of the polycyclic aromatic hydrocarbon
      fluoranthene. Previously unexposed fish and fish surviving acute exposure to
      fluoranthene were presented with three different concentrations of fluoranthene.
      Both groups of fish avoided fluoranthene. Pre-exposure did not enhance or
      diminish avoidance of fluoranthene. The lowest concentration of fluoranthene
      which produced an avoidance response was 14.7 mu/l, and the concentration of
      fluoranthene which did not produce an avoidance response was 8.6 micrograms/l.
      These results were comparable to the LOEC for survival in 7-day fathead embryo
      larval growth and survival tests for fluoranthene. Thus, a fathead minnow could
      escape from areas highly contaminated with fluoranthene and have a better
      opportunity to survive, whereas fish would fail to avoid areas where fluoranthene
      concentrations are below 8.6 micrograms/l and suffer further toxicosis.

PMID- 7623737
TI  - Neuropsychological evaluation of preschoolers with fetal alcohol syndrome.
AB  - Children with Fetal Alcohol Syndrome (FAS) manifest a variety of central nervous
      system deficits which may include mental retardation, perceptual, linguistic and
      fine motor deficits, as well as behaviour problems. The neuropsychological
      performance of to preschool-aged children with FAS was compared to age, sex, and
      race-matched controls. Profile analysis revealed significant deficits in the FAS
      group on measures of intelligence and linguistic abilities. Comparison of group
      profiles revealed that the FAS group displayed impaired visual-motor integration
      in the presence of average visual-perceptual matching. The FAS children were also
      reported to exhibit a greater frequency of behaviour problems compared to
      controls. Although the FAS group were significantly growth delayed, the often
      reported association between cognitive abilities and skeletal growth was not
      evident. These results indicate that preschoolers with FAS display a distinct
      pattern of impairments, and understanding of this unique ability profile is
      important for the development of support and intervention programs for these
      patients and their families.

PMID- 7623738
TI  - Trimethyltin disrupts loudness recruitment and auditory threshold sensitivity in
      guinea pigs.
AB  - Trimethyltin (TMT) impairs auditory thresholds within minutes of systemic
      administration. However, there are no data which relate to the output of the
      auditory nerve at sound levels above threshold. In this experiment, we evaluated
      the functional effects of TMT on the auditory threshold by identifying the sound
      level which just produced a detectable compound action potential (CAP). We also
      assessed outer hair cell function by measuring the cochlear microphonic (CM), a
      nonpropagated ac potential which is phase-locked to the stimulus. Finally, we
      measured the growth of the N1 amplitude as a function of stimulus intensity at
      levels above threshold and of the summating potential (SP), a dc potential which
      has multiple generators. To isolate cochlear from systemic effects of TMT, the
      agent was applied directly to the round window, a structure separating the middle
      and inner ear, of anaesthetized guinea pigs. We show that TMT applied to the
      round window membrane can disrupt the function of the cochlea. Measurements of
      auditory function at supra-threshold levels showed clearly that TMT reduced the
      amplitude of N1 while having no measurable effect on the SP. These findings
      indicate that TMT blocks the recruitment of neuronal elements by loud sound. This
      pattern of impairment differs from that observed with aminoglycoside antibiotics,
      hypothermia, and presbycusis in which loudness recruitment has been reported.

PMID- 7623739
TI  - Interaction of chlorphenvinphos with cholinergic receptors in the rabbit
      hypothalamus.
AB  - The purpose of this study was to find out whether chlorphenvinphos (CVP), an
      organophosphorous pesticide, interacts with the muscarinic cholinergic receptors
      in CNS. To attain this goal, the effects of intrahypothalamic injections of
      oxotremorine (Ox), a muscarinic agonist, and physostigmine (Phys), a carbamate
      anticholinesterase, were compared with those produced by intrahypothalamic
      injections of CVP in the rabbit. It was found that the infusion of Ox (20
      micrograms) as well as Phys (200 micrograms) into the anterior hypothalamus leads
      to an increase in the 4-7 Hz theta rhythm in the hippocampus and to the
      appearance of behavioral symptoms suggestive of a threat response. In the case of
      Ox, the effects could be prevented by injections of 20 micrograms scopolamine, a
      muscarinic antagonist. Pretreatment of the hypothalamus with 100 micrograms
      hemicholinium (HC-3) did not prevent the effects of Phys injected 2 h later. (HC
      3 prevents the resynthesis of acetylcholine by blocking choline reuptake. This
      leads to a gradual depletion of ACh stores and to an inhibition of the
      cholinergic transmission). It suggests that Phys activates directly postsynaptic
      muscarinic receptors. Intrahypothalamic injections of CVP in doses of up to 1360
      micrograms produced no overt changes in behavior nor in the hippocampal EEG of
      the rabbit and did not prevent the effect of subsequent injections of Ox. This
      suggests that CVP is neither an agonist nor antagonist of the muscarinic
      receptors in the rabbit hypothalamus.

PMID- 7623740
TI  - 3-Nitropropionic acid produces indirect excitotoxic damage to rat striatum.
AB  - The mechanism of striatal damage induced by 3-nitropropionic acid (3-NPA) was
      studied in rats by neuropathological and neurochemical methods. Neuronal
      shrinkage with astrogliosis was observed in striatum after local injection of 0.5
      5 mumol 3-NPA. Decortications involving dorsal and lateral aspects of frontal
      cortex or both frontal and parietal cortices significantly decreased the severity
      of striatal injuries induced by 3-NPA. This result suggests that corticostriatal
      projections play an important role in the development of striatal damage. No
      significant increase of glutamate and aspartate in striatal dialysates was
      observed, which indicated that 3-NPA may affect the postsynaptical sites and make
      the striatal neurons more vulnerable to endogenous levels of glutamate. Both of
      these findings suggested that 3-NPA produces indirect excitotoxic lesion to
      striatum. An increase of dopamine found in striatal dialysates may also be
      related to the occurrence of striatal damage.

PMID- 7623741
TI  - Effects of prenatal exposure to xylene on postnatal development and behavior in
      rats.
AB  - The effects of prenatal exposure to the organic solvent xylene (dimethylbenzene,
      CAS-no 1330-20-7) on postnatal development and behavior in rats were studied.
      Pregnant rats (Mol:WIST) were exposed to 500 ppm technical xylene 6 h per day on
      gestation days 7-20. The dose level was selected so as not to induce maternal
      toxicity or decrease the viability of offspring. In the exposed offspring, a
      delay in the ontogeny of the air righting reflex, a lower absolute brain weight,
      and impaired performance in behavioral tests for neuromotor abilities (Rotarod)
      and for learning and memory (Morris water maze) were found. Generally, the
      effects were most marked in the female offspring.

PMID- 7623742
TI  - Are the effects of toluene on the vestibulo and opto-ocular motor system
      inhibited by the action of GABAB antagonist CGP 35348?
AB  - The acute effects of toluene and a selective GABAB-antagonist, CGP 35348, on the
      vestibulo and opto-ocular motor (VOOM) system in rats were investigated by
      recording of compensatory eye-movements during vestibular and optokinetic
      stimulations. It has previously been demonstrated that toluene enhances the
      performance of the basic vestibulo-oculomotor reflex (VOR) and depresses the
      effects of the visual input to this reflex. It has been proposed that these
      effects are caused by alterations of the GABA-transmission system in the
      cerebellum. It has now been demonstrated that the exaggerating effects of toluene
      on the VOR, tested by angular horizontal acceleration/deceleration of the animals
      in darkness, are inhibited by CGP 35348 in a dose related way. On the contrary,
      the depressing effects on the visual input, tested by optokinetic stimulation, by
      angular acceleration/deceleration with a simultaneous conflicting visual
      stimulation and by eliciting saccades, could not be prevented by CGP 35348. The
      results support the hypothesis that toluene causes some of the effects on the
      VOOM system by influence on the GABA-transmission. The findings are in agreement
      with a recent report of increased levels of extracellular GABA in the cerebellar
      cortex during exposure to toluene.

PMID- 7623743
TI  - TV violence.

PMID- 7623744
TI  - Stop the media violence.

PMID- 7623745
TI  - Babies on the verge of having babies.

PMID- 7623746
TI  - Health status of surburban Hennepin County adolescents.

PMID- 7623747
TI  - Guidelines for adolescent preventive services. Addressing youth's risky
      behaviors.

PMID- 7623748
TI  - Could one wrong decision send you to jail?

PMID- 7623749
TI  - Easing the growing pains.

PMID- 7623750
TI  - The doctor is "in" when it comes to adolescents.

PMID- 7623751
TI  - Kids shooting kids. A surgeon's response.

PMID- 7623752
TI  - [The patient with internal pathology in dental practice: useful notes to avoid
      emergency situations].
AB  - The authors examine the emergencies following oral surgery procedures in patients
      with internal pathology due to allergies, heart or liver diseases, diabetes,
      haemorrhages and hormonal disorders, organ transplant or paraphysiological
      conditions like pregnancy. In this work they report the specific treatments
      useful to avoid this emergencies.

PMID- 7623753
TI  - [Nonfamilial cherubism. A clinical case report].
AB  - The authors report a rare case of non-familial cherubism with a six-year follow
      up. After an analysis of the hereditary transmission of the disease, the authors
      evaluate the anatomopathological and radiological characteristics and
      differential diagnosis, and then discuss possible therapies in the light of the
      latest research. They underline the important role of CT in identifying lesions
      which may not be diagnosed by simple X-ray with orthopantomography and highlight
      the importance of taking extreme care to conserve as much dental and bone tissue
      as possible during surgery.

PMID- 7623754
TI  - [Epidermoid carcinoma of the oral cavity. Considerations of the role of the
      papillomavirus].
AB  - Human papilloma virus (HPV) may have an important role in oral carcinoma
      etiology. Our work compares the presence of HPV in the epithelium of oral mucosa
      of patients with oral carcinoma with other factors of risk (smoking, alcohol,
      chronic mucosal trauma). We studied 33 patients operated for oral cancer at St.
      Salvatore Hospital in l'Aquila, in January-December 1990. The presence of HPV was
      proved by a direct valuation of morphological signs (coilocytosis, nuclear
      inclusions, etc.) and by immunohistochemical technique with primary antibodies
      against structural virus antigens. Among the 33 patients 19 (57.6%) were positive
      for HPV and 14 (42.4%) were negative. Among the HPV positive subjects 13 were
      smokers, 11 usually assumed alcohol and 6 had chronic mucosal trauma. Among the
      HPV negative subjects 9 were smokers, 7 assumed alcohol and 3 had chronic mucosal
      trauma. The statistical evaluation of data showed the lack of significance of
      viral infection compared to other factors of risk. In spite of a few cases
      examined, we suppose that HPV doesn't play a primary role in oral cancerogenesis,
      but is a concomitant cause with other factors of risk.

PMID- 7623755
TI  - [The presence of Actinobacillus actinomycetemcomitans in subgingival bacterial
      plaque in relation to the amount of supragingival plaque].
AB  - Actinobacillus actinomycetemcomitans (Aa) is currently considered the principal
      bacterium involved in juvenile forms of periodontitis. Considering that
      supragingival and subgingival plaque are closely correlated, the aim of the
      present research has been to assess if a correlation can be recognized between
      the amount of supragingival plaque and the presence of Aa in subgingival plaque
      in young subjects. Thirty-three individuals participated in the study. In each
      subject's dentition two periodontal sites were chosen: one (test site) was
      randomly selected among those sites which displayed a Plaque Index (P1I) = 0;
      another site was similarly chosen among those which presented the highest P1I
      score (2 or 3). In each test and control site Gingival Bleeding Index (GBI) was
      recorded and a microbiological sampling of subgingival plaque was performed.
      After anaerobic culture of plaque samples, the occurrence of Aa in each test and
      control site and the proportional representation of the bacterium in total
      cultivable anaerobic flora were assessed. Results showed a statistically
      significant difference in the occurrence of Aa between test and control sites in
      the same oral cavity and a correlation between GBI positivity and Aa presence. In
      conclusion, according to other authors, Aa seems to be more frequently founded in
      subgingival plaque coming from periodontal sites where supragingival plaque in
      more abundant.

PMID- 7623756
TI  - [The use of fibrin glue in the treatment of angiomas of the oromaxillofacial
      area].
AB  - The authors discuss the indications for fibrin glue utilization in the sclerosing
      treatment of angiomas, with particular reference to cavernous and venous
      angiomas. The sclerosing agent may be employed in connection with embolization
      and subsequent surgery. The authors have successfully used the interstitial
      sclerosing technique to obtain the sclerosis of the thin threads of fibrous
      tissue stroma between blood vessels. The sclerosing therapy may cause the
      complete regression of "low flow" angiomas or, at least, a partial reduction that
      simplifies the ensuing surgical excision. In the case of partial regression of
      the angiomas obtained with the sclerosing therapy, the surgery of the remaining
      angioma causes a lower degree of bleeding; an increased reliability in the
      radicality of the intervention (due also to the reduced size of the lesion); and
      better results from an aesthetic-functional point of view.

PMID- 7623757
TI  - [A morphological analysis and assessment of the dentinal permeability of
      detergents and liners].
AB  - In this study we evaluated the morphological aspect at scanning electron
      microscopy (SEM) and the degree of permeability of the dentinal surface after
      treatment with different detergent solutions, liners and cleansers. In particular
      we tested new potassium oxalate products. The results obtained with in vitro
      tests showed that many detergents, liners and cleansers are able to maintain
      almost unaltered the smear layer, causing small modifications for the diameter
      and the number of dentinal tubules which are partially exposed. The materials we
      used were able to deterge the dentinal surface, as demonstrated by SEM analysis,
      but one of them was able to stabilize and to protect the surface. All tested
      products, except potassium oxalate, caused an increase in dentinal permeability,
      proving to exercise a potential by damaging action towards the dentine and the
      pulpal tissue. Only DDS was able to reduce the dentinal permeability, causing the
      formation of calcium oxalate precipitates which occlude the dentinal tubules.

PMID- 7623759
TI  - Heat-related mortality--Chicago, July 1995.
AB  - During July 12-16, 1995, Chicago experienced unusually high maximum daily
      temperatures, ranging from 93 F to 104 F (33.9 C to 40.0 C). On July 13, the heat
      index peaked at 119 F (48.3 C)--a record high for the city. This report describes
      the heat-related deaths reported by the Cook County Medical Examiner's Office
      (CCMEO) during this heat wave.

PMID- 7623758
TI  - [Experimentation and clinical analysis of the interrelationships between dental
      damage and celiac disease].
AB  - Celiac disease is characterized by gluten-dependent atrophy of the intestinal
      tufts. Aetiologically the genetic "habitus" of the subject has particular
      importance and, as rear as the pathogenesis is concerned, many theories, among
      which the most accredited one is "immunopathological", exist. According to what
      this last one provides, the cell-mediated immunity component is to be considered
      the true mediator of intestinal injury, whereas the antibody-mediated component
      and, in particular, anti-gliadin antibodies (AGA) and anti-endomysium antibodies
      (EMA), has a particular and pre-eminent diagnostic role. Just from this point of
      view the celiac disease appeared, with the progress of the studies, to be more
      and more fleeting, because of growing symptomatologic diversification. It is then
      interesting to take into account that the celiac disease seems to be able to
      maintain itself asymptomatic for the greatest part of life, perhaps, forever,
      configuring the appearance of silent celiac disease and contributing to specify
      the outline of the above-mentioned celiac "habitus". Recently, besides, close
      associations have been found between many different diseases and celiac disease.
      Even for such reasons we relied upon the indication of the ESPGAN in order to
      achieve a sure and standardized diagnosis of celiac disease. Early diagnosis of
      celiac disease is very important because it allows a normal psychophysical
      development and it avoids the strong incidence of lymphomas and other neoplasms
      of the gastrointestinal tractus which can characterize the natural story of
      celiac patients. From a more specifically odontological point of view,
      interesting manifestations exist in the ambit of celiac disease. This last may in
      fact appear associated particular signs, such as recurrent aphthae or plainly
      autoimmune diseases with even oral verification. There, however, a more frequent
      association between celiac disease and some lesions of the tooth enamel which
      occur in the period of the two stages of histodifferentiation and mineralisation,
      and they are, respectively, hypoplasias and opacities. Alteration of the enamel,
      in such stages, both in deciduous and in permanent sets of teeth may be caused by
      different "noxae"; hence it will be necessary to know how to distinguish between
      the dental lesions typical of celiac disease and the others. It is helpful the
      fact that the dental lesion, observed in the course of celiac disease, remembers
      conceptually the Chronologic Hypoplasia of the enamel. This pathologic form
      damages the enamel which is depositing, and evolving contemporaneously to the
      local or systemic "noxa" which is its remote cause.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 7623760
TI  - Translocation of coyote rabies--Florida, 1994.
AB  - Translocation of a rabies variant from one area to another has been identified
      increasingly in the United States. During November and December 1994, rabies was
      diagnosed in five dogs from two associated kennels in Florida; in addition, two
      other dogs being kept at one of the kennels died with suspected, but unconfirmed,
      rabies. Rabies virus recovered from the five dogs was identified as a variant not
      previously found in Florida but endemic in coyotes (Canis latrans) in south
      Texas. The suspected source of infection was translocation of infected coyotes
      from Texas to Florida. This report summarizes the findings of an investigation of
      these cases by the Alachua County Public Health Unit, the Florida Department of
      Health and Rehabilitative Services, and CDC.

PMID- 7623761
TI  - Laboratory practices for diagnosis of tuberculosis--United States, 1994.
AB  - The increase in cases of tuberculosis (TB) during 1985-1992 and the emergence of
      multidrug-resistant Mycobacterium tuberculosis strains led to recommendations for
      rapid laboratory testing to support control efforts and selection of proper
      therapy (1,2). Many laboratories have adopted the recommendations to use rapid
      acid-fast bacilli (AFB) smears, growth detection (i.e., primary culture),
      identification, and drug-susceptibility testing for M. tuberculosis (3). The
      regulations implementing the 1988 Clinical Laboratory Improvement Amendments*
      (CLIA) require all laboratories that perform any mycobacteriology testing to
      enroll in federally approved proficiency testing (PT) programs. This report
      summarizes information reported by the laboratories to PT programs in the United
      States about their practices for M. tuberculosis.

PMID- 7623762
TI  - Recommendations for test performance and interpretation from the Second National
      Conference on Serologic Diagnosis of Lyme Disease.

PMID- 7623763
TI  - Regulation of adenylyl cyclase type VI activity during desensitization of the A2a
      adenosine receptor-mediated cyclic AMP response: role for protein phosphatase 2A.
AB  - We reported earlier that inhibition of adenylyl cyclase activity is a mechanism
      involved in desensitization of the A2a adenosine receptor-mediated cAMP response
      (A2a desensitization) in rat pheochromocytoma PC-12 cells. Here, we investigated
      the molecular mechanism that modulates adenylyl cyclase activity during A2a
      desensitization. Reversible inhibition of forskolin-evoked adenylyl cyclase
      activity in desensitized cells occurred after incubation with an A2a-selective
      adenosine agonist (CGS21680). However, when okadaic acid (a relatively protein
      phosphatase 2A-specific phosphatase inhibitor) was added after agonist removal,
      adenylyl cyclase activity did not recover. Okadaic acid caused significant dose
      dependent inhibition of adenylyl cyclase activity in intact PC-12 cells.
      Prolonged exposure of okadaic acid-treated PC-12 cells to adenosine agonists did
      not evoke further inhibition, suggesting that the inhibition of adenylyl cyclase
      activity during A2a desensitization may operate through a pathway that overlaps
      with the increased phosphorylation caused by okadaic acid. Inclusion of calcium
      in the adenylyl cyclase assay significantly inhibited cyclase activity.
      indicating that PC-12 cells contain Ca(2+)-inhibitable type VI adenylyl cyclase
      (AC6). This was confirmed by polymerase chain reaction-based detection of AC6
      cDNA. Furthermore, incubation of PC-12 cell membrane fractions with purified
      protein phosphatase 2A or coexpression of protein phosphatase 2A with AC6 in COS
      1 cells significantly increased AC6 activity. To reduce the possible influence of
      Gs alpha protein, we substituted guanosine-5'-O-(2-thio)diphosphate and MnCl2 for
      GTP and MgCl2, respectively, in some cyclase assays and found that the
      suppression of AC6 during A2a desensitization and okadaic acid treatment remained
      largely unchanged. Taken together, these data suggest that phosphorylation of AC6
      might account for the inhibition of adenylyl cyclase activity during A2a
      desensitization in PC-12 cells.

PMID- 7623764
TI  - alpha-Conotoxins selectively inhibit one of the two acetylcholine binding sites
      of nicotinic receptors.
AB  - Muscle subtypes of the nicotinic acetylcholine receptor contain two acetylcholine
      binding sites that can be distinguished pharmacologically. The affinities of
      several alpha-conotoxins for the two acetylcholine binding sites on nicotinic
      receptors from BC3H1 cells and Torpedo electric organ were investigated. alpha
      Conotoxins MI, GI, and SIA each inhibited the binding of 125I-alpha-bungarotoxin
      to nicotinic acetylcholine receptors on BC3H1 cells with two distinct and
      independent affinities, which differed by > 10,000-fold. The affinities of alpha
      conotoxins SI and SII were significantly lower and the differences in the
      affinities of each of these toxins for the two sites were < 400-fold. alpha
      Conotoxins MI, GI, SIA, and SI had higher affinity for the acetylcholine binding
      site near the alpha/delta subunit interface of nicotinic receptors from BC3H1
      cells. However, when assessed using nicotinic receptors from Torpedo electric
      organ, alpha-conotoxin MI displayed higher affinity for the acetylcholine binding
      site near the alpha/gamma subunit interface. These observations suggest that
      species variations in the sequences of the gamma and delta subunits resulted in a
      dramatic reversal of the relative affinities of the alpha-conotoxins for each
      acetylcholine binding site. Some of the practical implications of these
      observations are discussed.

PMID- 7623766
TI  - Erythro-9-(2-hydroxy-3-nonyl)adenine inhibits cyclic GMP-stimulated
      phosphodiesterase in isolated cardiac myocytes.
AB  - Recently, an inhibitor of adenosine deaminase, erythro-9-(2-hydroxyl-3
      nonyl)adenine (EHNA), was shown to selectively block the activity of purified
      cGMP-stimulated phosphodiesterase (PDE) (cGS-PDE, or PDE2) in human and porcine
      heart [J. Mol. Cell. Cardiol. 24 (Suppl. V):102 (1992)]. Because cGS-PDE was
      found to mediate the cGMP-induced inhibition of L-type Ca2+ current (Ica) in frog
      ventricular cells, we tested the effects of EHNA in this preparation. Ica was
      measured using the whole-cell patch-clamp technique and a perfusing pipette. EHNA
      (0.3-30 microM) had no significant effect on either basal Ica or isoprenaline (1
      nM)- or cAMP (10 microM)-elevated Ica. However, EHNA dose-dependently (IC50
      approximately 3 microM) reversed the inhibitory effect of cGMP on cAMP-stimulated
      Ica. EHNA (30 microM) also blocked the inhibitory effect of NO donors, such as
      sodium nitroprusside (1 mM) and 3-morpholinosydnonimine (30 microM), on
      isoprenaline-stimulated Ica. In addition, EHNA dose-dependently (IC50
      approximately 4-5 microM) inhibited the cGMP-induced stimulation of PDE activity
      in frog ventricle particulate fraction, as well as purified soluble cGS-PDE.
      However, EHNA (up to 30 microM) did not modify the activities of three other
      purified soluble PDE isoforms. Moreover, EHNA did not change the Ka (40 nM) for
      cGMP activation of cGS-PDE, which suggests that EHNA does not inhibit cGS-PDE by
      displacing cGMP from the allosteric regulator site. Because adenosine did not
      mimic the effects of EHNA on Ica or PDE activity, it is unlikely that the effects
      of EHNA are due to adenosine deaminase inhibition. We conclude that EHNA acts
      primarily to inhibit cGS-PDE in intact cardiac myocytes. This compound should be
      useful in evaluating the physiological role of cGS-PDE in various tissues.

PMID- 7623765
TI  - Phenytoin-initiated DNA oxidation in murine embryo culture, and embryo protection
      by the antioxidative enzymes superoxide dismutase and catalase: evidence for
      reactive oxygen species-mediated DNA oxidation in the molecular mechanism of
      phenytoin teratogenicity.
AB  - A murine embryo culture model was used to investigate phenytoin-initiated
      embryonic DNA oxidation and dysmorphogenesis and to determine the
      embryoprotective potential of superoxide dismutase and catalase, which detoxify
      reactive oxygen species. Gestational day 9.5 CD-1 embryos were cultured for up to
      24 hr at 37 degrees in medium containing phenytoin (20 micrograms/ml, 80 microM)
      or its vehicle (0.002 N NaOH). Embryos cultured for 24 hr were examined for
      embryotoxicity. After varying durations of incubation, embryonic DNA was isolated
      and purified, and DNA oxidation was determined from the formation of 8-hydroxy-2'
      deoxyguanosine (8-OH-2'-dG). Control embryos showed an early increase in 8-OH-2'
      dG levels that was maximal between 2 and 4 hr, followed by a small but
      significant decrease over 24 hr, with no evidence of embryopathy. Phenytoin
      treated embryos within 4 hr also demonstrated maximal 8-OH-2'-dG formation, which
      was substantially greater than that of controls, with a maximal 3-fold increase
      over controls at 24 hr (p < 0.05). In wash-out studies, embryos removed from the
      phenytoin-containing medium after 4 hr and then cultured in phenytoin-free medium
      for an additional 20-hr period showed no decrease in either 8-OH-2'-dG levels or
      embryotoxicity, compared with embryos incubated in the presence of phenytoin for
      24 hr. Embryos exposed to phenytoin demonstrated substantial dysmorphogenesis, as
      evidenced by decreases in anterior neuropore closure, turning, yolk sac diameter,
      crown-rump length, and somite development (p < 0.05). Superoxide dismutase and
      catalase virtually eliminated phenytoin-initiated 8-OH-2'-dG formation and
      reduced or completely eliminated all phenytoin-initiated dysmorphological
      anomalies (p < 0.05). These results suggest that embryonic DNA oxidation
      constitutes teratologically important molecular target damage, and they provide
      the first direct evidence that free radical-mediated oxidative stress plays a
      critical role in phenytoin teratogenesis.

PMID- 7623767
TI  - Omega-grammotoxin SIA blocks multiple, voltage-gated, Ca2+ channel subtypes in
      cultured rat hippocampal neurons.
AB  - Omega-Grammotoxin SIA is a peptide isolated from tarantula venom on the basis of
      its ability to block the voltage-gated Ca2+ channels that mediate glutamate
      release. To determine the Ca2+ channel subtype selectivity of omega-grammotoxin
      SIA, whole-cell Ba2+ current (IBa) was measured in cultured rat hippocampal
      neurons. Selective Ca2+ channel blockers were used to identify components of IBa
      mediated by Ca2+ channel subtypes. omega-Agatoxin IVA at 30 nM, 1 microM omega
      conotoxin GVIA, and 3 microM omega-contoxin MVIIC, applied consecutively, each
      elicited a fractional increase in the cumulative block of IBa, identifying
      components of IBa mediated by P-, N-, and Q-type calcium channels. omega
      Grammotoxin at 1 microM, a maximally effective concentration, blocked 52% of IBa.
      omega-Conotoxin MVIIC and the combination of omega-conotoxin GVIA and micromolar
      omega-agatoxin IVA blocked 52% and 54% of IBa, respectively, and block of IBa by
      omega-grammotoxin SIA was mutually occlusive of block of IBa by either treatment,
      both of which block N-, P-, and Q-type Ca2+ channels. The L channel blocker
      nimodipine produced identical block of IBa in the presence and absence of omega
      grammotoxin SIA. These results indicate that omega-grammotoxin SIA blocks N-, P-,
      and Q-type but not L-type voltage-gated calcium channels. Block of IBa by omega
      grammotoxin SIA was faster in onset and less sensitive to external divalent
      cation concentrations than was block by omega-conotoxin MVIIC, and it was rapidly
      and substantially reversible. Rapid onset, relative insensitivity to divalent
      cation concentrations, and reversibility render omega-grammotoxin SIA a useful
      tool for inhibition of neuronal voltage-gated Ca2+ channels.

PMID- 7623768
TI  - Type 4a metabotropic glutamate receptor: identification of new potent agonists
      and differentiation from the L-(+)-2-amino-4-phosphonobutanoic acid-sensitive
      receptor in the lateral perforant pathway in rats.
AB  - Before the discovery of the metabotropic glutamate receptors (mGluRs), the
      glutamate analogue L-2-amino-4-phosphonobutanoic acid (L-AP4) was identified as a
      potent presynaptic inhibitor of evoked synaptic transmission in the lateral
      perforant pathway in rats. The localization and L-AP4 sensitivity of the mGluR4a
      subtype of mGluRs were consistent with the hypothesis that this receptor mediates
      the synaptic depressant effects of L-AP4 in the lateral perforant pathway. In the
      present study, the pharmacology of mGluR4a expressed in baby hamster kidney 570
      cells was characterized and compared with that previously reported for the
      lateral perforant pathway responses. The endogenous excitatory amino acid L
      aspartate was inactive at mGluR4a, whereas L-homocysteic acid was only 5-fold
      less potent than L-glutamate. These data suggest that L-homocysteic acid may be
      an endogenous agonist at mGluR4a. Of the 30 L-AP4 analogues examined, several
      compounds were identified as agonists at mGluR4a. The cyclopropyl-AP4 analogue
      (Z)-(+/-)-2-amino-2,3-methano-4-phosphonobutanoic acid inhibited forskolin
      stimulated cAMP production with an EC50 of 0.58 microM, which is comparable to
      that of L-AP4 (EC50 = 0.43 microM). Two other cyclic analogues of L-AP4 were
      approximately 10-fold less potent as agonists at mGluR4a, i.e., (+/-)-1-amino-3
      (phosphonomethylene)cyclobutanecarboxylic acid (EC50 = 4.4 microM) and (E)-(+/-)
      2-amino-2,3-methano-4-phosphonobutanoic acid (EC50 = 7.9 microM). Comparison of
      the potencies of the compounds for activation of mGluR4a with their potencies for
      inhibition of lateral perforant pathway responses demonstrates that some
      compounds have comparable activities in the two systems, whereas several
      compounds are at least 10-fold more potent in one of the systems. In addition,
      although the mGluR antagonist (+)-alpha-methyl-4-carboxyphenylglycine blocked the
      effects of L-AP4 in the lateral perforant pathway, it did not block the effects
      of L-AP4 at the cloned receptor. These data provide evidence that mGluR4a does
      not mediate the effects of L-AP4 in the lateral perforant pathway, they provide
      new tools to identify the function of these receptors in the mammalian central
      nervous system, and they indicate that the effects of L-AP4 in the lateral
      perforant pathway are mediated by a (+)-alpha-methyl-4-carboxyphenylglycine
      sensitive receptor.

PMID- 7623769
TI  - Serotonergic antagonists differentially inhibit spontaneous activity and decrease
      ligand binding capacity of the rat 5-hydroxytryptamine type 2C receptor in Sf9
      cells.
AB  - The activities of serotonergic antagonists as inverse agonists at the rat 5
      hydroxytryptamine (5-HT)2C serotonin receptor were compared with their potencies
      in promoting receptor "down-regulation," after expression of the recombinant
      receptor in the baculovirus/Sf9 insect cell system. Baculovirus expression
      yielded high levels of 5-HT2C receptors (up to 10(6) receptors/cell), which were
      functionally coupled to polyphosphoinositide turnover in Sf9 cells through a
      pertussis toxin-insensitive pathway. The expressed receptor exhibited spontaneous
      activation of inositol phosphate production, which was inhibited in a dose
      dependent manner by serotonergic antagonists, consistent with inverse agonist
      activity. The potencies of antagonists as inverse agonists correlated with their
      respective binding affinities determined in competition binding studies with
      membrane preparations. The maximal inhibition of spontaneous activity ranged from
      32% inhibition for mianserin to no effect for spiroxatrine, indicating that
      antagonists differ in their intrinsic inverse efficacies. Antagonist treatment of
      intact Sf9 cells or membranes containing the 5-HT2C receptor, followed by washout
      of residual drug, resulted in a decrease (up to 90%) in the number of binding
      sites for [3H]mesulergine and [3H]5-HT, with no change in the affinity for
      [3H]mesulergine. The decrease in binding was irreversible, was not due to the
      presence of residual antagonist, and was not observed after treatment with
      agonists. This effect of antagonists in membranes was dose dependent, but the
      rank order of potency was clearly different from that for inverse agonist
      activity, indicating that the two effects reflect distinct actions of antagonists
      at the 5-HT2C receptor. The relative abilities of antagonists to produce loss of
      binding showed a good correlation with their reported abilities to down-regulate
      5-HT2 receptors in vivo after chronic treatment, suggesting that these actions
      reflect the same underlying process.

PMID- 7623770
TI  - Effects of n-dodecylguanidine on A-type potassium channels: role of external
      surface charges in channel gating.
AB  - n-Dodecylguanidine (C12-G) is an amphipathic compound with a guanidine moiety,
      which is positively charged at physiological pH, and a hydrophobic side chain.
      Its effects on an A-type K+ channel clone (rKv1.4) expressed in Xenopus oocytes
      were examined. C12-G caused a concentration-dependent (1-20 microM) positive
      shift in the voltage dependences of the following channel properties: activation,
      inactivation, rate of decay during depolarization, and rate of recovery from
      inactivation. C12-G was effective when added to the bath solution but was without
      effect when applied to the cytoplasm of oocytes, indicating an extracellular site
      of action. The effects of C12-G were antagonized by elevation of the
      extracellular Mg2+ concentration and by external guanidine ions but were
      augmented by lowering of the ionic strength of the external solution. C12-G did
      not affect the instantaneous current-voltage relationship for rKv1.4 or the time
      constant of decay during strong depolarizations, when the voltage dependence of
      channel activation approached a plateau. Our observations suggest that C12-G
      exerts its actions by causing a positive shift in the external surface potential
      around rKv1.4, without altering the ion permeation process or voltage-independent
      transition steps. In canine ventricular myocytes, C12-G caused changes in the
      function of a native A-type K+ channel similar to those seen with rKv1.4.
      However, C12-G had negligible effects on the voltage dependence of the slow
      delayed-rectifier K+ channel in the same cell type, suggesting that the actions
      of C12-G are not nonspecific.

PMID- 7623771
TI  - B9209-005, an azido derivative of the chemosensitizer dexniguldipine-HCl,
      photolabels P-glycoprotein.
AB  - P-glycoprotein is an energy-dependent drug extrusion pump for a variety of
      anticancer drugs and is involved in the development of multidrug resistance in
      cancer. Dexniguldipine-HCl is a potent chemosensitizer for P-glycoprotein
      mediated multidrug resistance in vitro, and clinical phase I/II trials are
      underway. To investigate the mechanisms of chemosensitization and to identify the
      binding sites for dexniguldipine-HCl on target proteins involved in
      chemosensitization, [3H]B9209-005, an azido derivative of dexniguldipine-HCl, was
      synthesized and used as a photoaffinity ligand. In two models of multidrug
      resistance reversal, i.e., sensitization to vincristine and modulation of
      rhodamine-123 uptake, B9209-005 and dexniguldipine-HCl showed identical
      biological activities. Photoaffinity labeling experiments with [3H]B9209-005 in
      cell membranes from multidrug-resistant CCRF ADR-5000 cells, in comparison with
      labeling experiments with [3H]azidopine (an established photoaffinity ligand for
      P-glycoprotein), showed that [3H]B9209-005 labeled two proteins, with apparent
      molecular masses of 170 and 95 kDa. The pharmacological specificity of labeling
      was demonstrated by inhibition of photoincorporation by several cytostatic drugs
      transported by P-glycoprotein, as well as by chemosensitizers.
      Immunoprecipitation of the labeled proteins with the P-glycoprotein-specific
      monoclonal antibody C 219 and with a site-directed polyclonal antibody to the
      amino-terminal sequence of P-glycoprotein (amino acids 389-406) identified these
      proteins as intact P-glycoprotein and the amino-terminal fragment thereof. No
      specific labeling was obtained in the drug-sensitive parent cell line CCRF-CEM,
      which is devoid of significant P-glycoprotein expression. Maximal labeling of 17
      pmol of the 170-kDa protein/mg of crude membrane protein was obtained. The
      affinity of [3H]B9209-005 for binding to and photoincorporation into P
      glycoprotein was 5-fold greater than that of [3H]azidopine, and
      photoincorporation of [3H]B9209-005 showed a different photoincorporation
      pattern, compared with [3H]azidopine, in that the latter compound was
      incorporated specifically into the carboxyl-terminal 55-kDa fragment of P
      glycoprotein. In contrast to [3H]azidopine, no specific labeling of this fragment
      was obtained with [3H]B9209-005, indicating different binding sites for or
      different photoincorporation of the two dihydropyridine ligands. Because B9209
      005 carries the photoreactive azido group in the dihydropyridine moiety, whereas
      the azido group of azidopine is located in the side chain, these results suggest
      that the dihydropyridine moiety of the two compounds probably interacts with the
      amino-terminal part of P-glycoprotein, whereas the side chains react
      preferentially with the carboxyl-terminal 55-kDa fragment.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 7623772
TI  - Topoisomerase II DNA cleavage stimulation, DNA binding activity, cytotoxicity,
      and physico-chemical properties of 2-aza- and 2-aza-oxide-anthracenedione
      derivatives.
AB  - The cytotoxic activity of mitoxantrone and related anthracenediones has been
      ascribed to the ability of these compounds to interfere with DNA topoisomerase II
      function, resulting in DNA cleavage stimulation. The molecular details of enzyme
      inhibition by these intercalating agents remain to be defined. In an attempt to
      identify the structural determinants for optimal activity, the molecular and
      cellular effects of a series of heteroanalogues bearing different side-chains
      were examined in relation to the physico-chemical and DNA binding properties of
      these compounds. The results indicated that substitution of a pyridine ring for
      the dihydroxyphenylene ring in the planar chromophore caused a marked reduction
      of cytotoxic activity and of the ability to stimulate topoisomerase II-mediated
      DNA damage in intact cells and with simian virus 40 DNA in vitro. Although all
      tested derivatives were shown to intercalate into DNA, their DNA binding
      affinities were appreciably lower than that of mitoxantrone. The behavior of 2
      aza derivatives more closely resembled that of ametantrone, suggesting that the
      potency of agents of this class is influenced more by the presence of hydroxyl
      groups than by the phenylene ring. The observation that a dramatic reduction (or
      loss) of the ability of aza derivatives to stimulate DNA cleavage is associated
      with a marked reduction of cytotoxic potency supports a primary role of
      topoisomerase II-mediated effects in the mechanism of action of the effective
      agents of this class. Because appreciable cytotoxic activity and significant in
      vivo antitumor efficacy are retained by compounds inactive (or poorly active) in
      inhibition of topoisomerase II, these results are consistent with multiple
      effects of anthracenediones at the cellular level.

PMID- 7623773
TI  - Role of protein kinase C subtypes alpha and delta in the regulation of bradykinin
      stimulated phosphoinositide breakdown in astrocytes.
AB  - Cultured astrocytes express bradykinin (BK) receptors coupled to phospholipase C
      (PLC)-mediated phosphoinositide (PI) hydrolysis. Short term (10- or 90-min)
      treatment of cells with 1 microM 12-O-tetradecanoylphorbol-13-acetate (TPA)
      decreased BK-induced PI breakdown, but this inhibitory action was lost after 3-hr
      TPA treatment. Extended (6- or 24-hr) pretreatment resulted in marked
      potentiation of the BK response. Western blot analysis using protein kinase C
      (PKC) isozyme-specific antibodies indicated that astrocytes express PKC-alpha,
      PKC-delta, and PKC-zeta. With TPA treatment of the cells for various times (10
      min, 90 min, 3 hr, 6 hr, or 24 hr), translocation of PKC-alpha and PKC-delta from
      the cytosol to the membrane was seen after 10- or 90-min treatment and
      restoration to basal levels in the membrane fraction was seen after 3-hr
      treatment. However, partial or complete down-regulation of PKC-alpha and PKC
      delta was seen after 6- or 24-hr treatment, respectively. No translocation or
      down-regulation of PKC-zeta was seen after either short term or long term TPA
      treatment. The inactive phorbol ester alpha-TPA had no effect on BK-induced PI
      hydrolysis or on the translocation or down-regulation of PKC-alpha and PKC-delta.
      These results suggest that, in unstimulated astrocytes, both PKC-alpha and PKC
      delta, but not PKC-zeta, may exert tonic inhibition of BK-mediated PI turnover.
      After 10- or 90-min TPA treatment, AIF4(-)--but not Ca2+ ionophore-induced PI
      hydrolysis was inhibited, whereas [3H]BK binding was unaffected, indicating that
      the site of action of PKC-alpha and PKC-delta in the BK receptor/G protein/PLC
      pathway is after the receptor and before PLC, i.e., the G protein. After down
      regulation of PKC-alpha and -delta, increases in both AIF4(-)-induced inositol
      phosphate formation and [3H]BK binding contributed to marked potentiation of BK
      induced PI responses. Scatchard plot analysis showed an increase in both the
      maximal number of binding sites and the binding affinity. Both the up-regulation
      of [3H]BK binding and the subsequent BK-induced PI turnover were blocked by 0.5
      microM cycloheximide, a protein synthesis inhibitor. The increase in AIF4(-)
      induced PI hydrolysis after 24-hr TPA treatment was also inhibited by
      cycloheximide, indicating that new synthesis of BK receptors and G proteins was
      required after down-regulation of PKC-alpha and PKC-delta.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 7623774
TI  - Targeted inactivation of the gene encoding the mouse alpha 2c-adrenoceptor
      homolog.
AB  - alpha 2-Adrenergic receptors (alpha 2-ARs) regulate a wide range of physiological
      functions and are targets for clinically important antihypertensive and
      anesthetic agents. Three genes encoding alpha 2-AR subtypes have been cloned in
      humans and mice, but the physiological significance of each subtype has not been
      completely characterized. The available agonist and antagonist compounds are not
      sufficiently subtype selective to allow the unambiguous dissection of these
      receptors in vivo. As an alternative approach, we have used gene targeting in
      embryonic stem cells to disrupt the Adra2c gene, which encodes the alpha 2c-AR
      subtype in mice. Adra2c-/Adra2c- animals do not express a functional alpha 2c-AR
      transcript, as detected by Northern blotting or reverse transcription-polymerase
      chain reaction analysis. In addition, these mice have markedly reduced
      [3H]rauwolscine binding in their caudate putamen and in other brain regions
      normally expressing Adra2c binding sites. Adra2c-/Adra2c- mice, however, are
      viable and fertile and appear grossly normal. Expression levels of Adra2a and
      Adra2b mRNA in brain and kidney are not altered by the Adra2c knockout. These
      data suggest that up-regulation of Adra2a or Adra2b does not compensate for the
      Adra2c deficiency and that the receptor encoded by Adra2c is not required for
      normal mouse development or for survival in a laboratory environment.

PMID- 7623775
TI  - Differentiation induces pituitary adenylate cyclase-activating polypeptide
      receptor expression in PC-12 cells.
AB  - The two forms of pituitary adenylate cyclase-activating polypeptide (PACAP),
      PACAP27 and PACAP38, are neuropeptide hormones related to the vasoactive
      intestinal peptide/secretin/glucagon family of peptides. PACAP receptors that are
      positively coupled to adenylyl cyclase and phospholipase C have been recently
      identified. We have investigated the expression of PACAP-Rs in undifferentiated
      and differentiated PC-12 cells. PACAP27 and PACAP38 failed to significantly
      increase cAMP or [3H]inositol monophosphate levels in undifferentiated PC-12
      cells treated with vehicle, insulin-like growth factor I, or epidermal growth
      factor but greatly elevated levels after differentiation with nerve growth factor
      (NGF) or basic fibroblast growth factor. PACAP responsiveness increased
      significantly after 24 hr of NGF treatment, reaching a maximum within 4 days. At
      this time of differentiation, the effect of PACAP was dose dependent between 1 nM
      and 0.1 microM, whereas vasoactive intestinal peptide, at the maximal dose of 10
      microM, slightly increased cAMP formation and failed to affect [3H]inositol
      monophosphate content. Radioreceptor assays, performed with 125I-PACAP27,
      revealed the induction of high affinity type I PACAP receptors in differentiated
      PC-12 cells. Using reverse transcription-polymerase chain reaction methodology,
      we showed the absence of type I PACAP receptor mRNAs in undifferentiated PC-12
      cells and the expression of PACAP-R-hop mRNA after NGF or basic fibroblast growth
      factor treatment. The increased PACAP responsiveness induced by these growth
      factors in PC-12 cells may therefore result from the expression of the PACAP-R
      hop isoform, positively coupled to both adenylyl cyclase and phospholipase C.

PMID- 7623776
TI  - Pituitary adenylate cyclase-activating polypeptide type I receptors mediate
      cyclic AMP-dependent enhancement of neuronal acetylcholine sensitivity.
AB  - Nicotinic acetylcholine (ACh) receptors (AChRs) on ciliary ganglion neurons are
      positively regulated by elevated cAMP levels. Vasoactive intestinal peptide (VIP)
      can act as a first messenger in the regulation, because application of 1 microM
      VIP rapidly increases both neuronal cAMP levels and ACh sensitivity. We now
      report that high affinity receptors for a close VIP relative, pituitary adenylate
      cyclase-activating polypeptide (PACAP), are present on ciliary ganglion neurons
      and mediate the cAMP-dependent modulation of AChRs. Consistent with the presence
      of PACAP type I receptors, binding studies revealed sites on the neurons having
      approximately 1000-fold higher affinity for the 38- and 27-amino acid forms of
      PACAP than for VIP, and cAMP radio-immunoassays demonstrated that PACAP38 and
      PACAP27 are approximately 600-fold more potent agonists for mobilizing neuronal
      cAMP than is VIP. In accord with their higher affinity and potency, PACAP38 and 
      27 (both at 10 nM) increased neuronal ACh sensitivity by approximately 50% within
      10 min, whereas VIP at the same low concentration was ineffective. The increased
      ACh sensitivity induced by 10 nM PACAP38 or PACAP27 or 1 microM VIP depends on
      coincident increases in cAMP levels, because treatment of neurons with adenylate
      cyclase inhibitors blocked both effects. The findings demonstrate the presence of
      functional PACAP type I receptors on ciliary ganglion neurons that preferentially
      recognize PACAP38 and -27 over VIP and act via adenylate cyclase to initiate cAMP
      dependent enhancement of AChR function. Finally, we detected PACAP38-like
      material in ciliary ganglia, suggesting a role for the peptide in modulating
      neuronal AChRs in vivo.

PMID- 7623777
TI  - Biphasic binding of 5-fluoro-2'-deoxyuridylate to human thymidylate synthase.
AB  - Thymidylate synthase (TS) is a homodimeric enzyme that catalyzes the reductive
      methylation of dUMP by N5,N10-methylene-5,6,7,8-tetrahydrofolic acid, to form
      dTMP. Inhibition of TS by the dUMP analog 5-fluoro-dUMP (FdUMP) occurs through
      the formation of a covalent ternary complex containing the nucleotide analog,
      N5,N10-methylene-5,6,7,8-tetrahydrofolic acid, and the enzyme; this complex is
      termed the inhibitory ternary complex (ITC). In the present report, the kinetics
      of FdUMP binding into an ITC with purified preparations of human TS were
      examined. Rapid chemical-quench techniques, as well as steady state binding
      methods, showed that the enzyme contains two distinct FdUMP binding sites with
      different affinities for the nucleotide analog. Binding to the first, or high
      affinity, site was rapid and reached a maximum stoichiometry of 1.0 mol of
      FdUMP/mol of dimer; binding to the second, or low affinity, site was much slower
      and reached a stoichiometry of 1.7 mol of FdUMP/mol of dimer. Rate constants for
      FdUMP binding to and dissociation from the ITC (kon and koff, respectively) were
      determined, as were equilibrium dissociation constants (Kd). A naturally
      occurring mutant form of TS, which contains a tyrosine to histidine substitution
      at residue 33 and renders cells relatively resistant to fluoropyrimidines,
      exhibited a lower affinity for FdUMP specifically at the second binding site,
      with little or no change at the first. Hill coefficients were < 1.0, with the His
      33 enzyme having a significantly lower coefficient than the wild-type enzyme. The
      results, in total, indicate that the two FdUMP binding sites on the TS dimer are
      nonequivalent. We suggest that such nonequivalence may be due to negative
      cooperativity, where nucleotide binding to the first subunit elicits a
      conformational change that results in reduced affinity for ligand at the second
      subunit. This negative cooperativity may be stronger for the His-33 mutant. Thus,
      the relative fluoropyrimidine resistance conferred by the His-33 substitution may
      be due to enhanced negative cooperative effects on FdUMP binding into the ITC,
      thereby reducing the effectiveness of the pyrimidine analog as an inhibitor of
      thymidylate biosynthesis.

PMID- 7623778
TI  - Relationship of the metabolism of vitamins C and E in cultured hepatocytes
      treated with tert-butyl hydroperoxide.
AB  - The relationship between the metabolism of alpha-tocopherol (alpha-T) (vitamin E)
      and that of ascorbic acid (vitamin C) was examined in cultured hepatocytes
      intoxicated with tert-butyl hydroperoxide (TBHP). Unlike vitamin E, the cellular
      content of vitamin C did not decline after overnight culturing of freshly
      prepared hepatocytes. In addition, this basal vitamin C content was not affected
      by the presence of alpha-T phosphate in the overnight culture medium.
      Supplementation of the overnight culture medium with vitamin C (10 microM to 10
      mM) increased the cellular content of vitamin C by > 1 order of magnitude.
      Increasing the cellular content of ascorbate increased the protection against
      TBHP toxicity, with or without the presence of a physiological content of vitamin
      E. In vitamin E-supplemented cells, a loss of alpha-T occurred within 15 min of
      exposure to TBHP and before the decrease in cellular ascorbate content. The
      vitamin C content declined in parallel with the loss of cell viability.
      Supplementation of the overnight culture medium with increasing concentrations of
      ascorbate progressively spared the depletion of alpha-T while preventing the cell
      killing. Pretreatment with the ferric iron chelator deferoxamine or the
      antioxidant N,N'-diphenyl-1,4-phenylenediamine prevented the loss of ascorbate
      and the cell killing by TBHP in hepatocytes either sufficient or deficient in
      alpha-T. However, neither alpha-T nor ascorbate prevented the accumulation of DNA
      single-strand breaks caused by TBHP, indicating that these vitamins do not
      effectively scavenge the TBHP-derived radicals responsible for DNA damage. The
      data in the present study indicate that vitamins E and C act as independent
      antioxidants and that ascorbate does not regenerate alpha-T in cultured rat
      hepatocytes.

PMID- 7623779
TI  - Voltage- and frequency-dependent pentobarbital suppression of brain and muscle
      sodium channels expressed in a mammalian cell line.
AB  - The voltage- and frequency-dependent interactions of pentobarbital with voltage
      gated sodium channels were examined in whole-cell patch-clamp recordings. Using
      rat brain IIA and rat muscle rSkM1 sodium channels expressed in stably
      transfected Chinese hamster ovary cell lines, it was found that pentobarbital
      reduced peak inward sodium currents with IC50 values of 1.2 mM (brain) and 1.0 mM
      (muscle). Analysis of steady state channel availability curves revealed two
      distinct effects of pentobarbital on both channel isoforms, i.e., a voltage
      independent current reduction and an additional hyperpolarizing shift in the
      voltage dependence of channel availability. The latter effect leads to a voltage
      dependence of pentobarbital potency. Pentobarbital was also found to slow channel
      recovery after depolarization, yielding an additional use-dependent component of
      current suppression. Use-dependent block was enhanced by higher stimulation
      frequencies, longer pulse durations, and more depolarized holding and pulse
      potentials. All effects were identical for both channels. These findings can be
      explained in terms of the modulated receptor hypothesis and are consistent with a
      preferential interaction of pentobarbital with the inactivated channel state. As
      a consequence, actual pentobarbital potency would depend largely on experimental
      conditions or, in vivo, on the physiological parameters of a particular cell.

PMID- 7623780
TI  - Studies on neuropeptide Y receptors in a mouse adrenocortical cell line.
AB  - The mouse adrenocortical Y-1 cell line has been found to express high affinity
      binding sites for neuropeptide Y (NPY). Pharmacological studies have shown that
      these NPY binding sites are of the Y1 type. Reverse transcription-polymerase
      chain reaction using primers specific for the rat Y1 receptor revealed that the
      NPY Y1 receptor mRNA is present in Y-1 cells. The Kd of the receptor for NPY was
      found to be 1.75 +/- 0.20 nM and the Bmax was 265 +/- 18 fmol/mg. The NPY Y1
      receptors in this adrenocortical cell line were shown to be coupled to pertussis
      toxin-sensitive G proteins. Stimulation of Y1 receptors resulted in the
      inhibition of forskolin- and adrenocorticotropic hormone (ACTH)-stimulated cAMP
      synthesis. NPY had no effect on basal steroid release from the Y-1 cells. At an
      ACTH concentration of 0.1 microM, NPY did not affect ACTH-stimulated steroid
      release, although NPY did inhibit cAMP production under the same hormonal
      conditions. cAMP profoundly affected the density of the NPY receptors in Y-1
      cells. Treatment of the cells with N6,2'-O-dibutyryl-cAMP or ACTH reduced the Y1
      receptor density by > 50%. On the other hand the steroid dexamethasone increased
      the density of Y1 receptors by 35%. Although additional detailed studies are
      necessary, these results may have interesting implications for the functions of
      ACTH, steroids, and NPY in the pituitary-adrenocortical axis.

PMID- 7623781
TI  - Thyroid hormone inhibits fatty acid synthase gene transcription in chicken liver.
AB  - The effect of triiodothyronine (T3) on regulation of fatty acid synthase in
      chicken liver was investigated. In hypothyroid animals, enzyme activity was about
      one half of that in euthyroid animals. T3 treatment increased the enzyme activity
      in hypothyroid animals. There is little difference in both the mRNA concentration
      and the transcription rate between euthyroid and hypothyroid animals. T3
      treatment markedly decreased both the mRNA concentration and the transcription
      rate in euthyroid and hypothyroid animals. These results suggested that T3
      maintained the normal level of enzyme expression primarily by stimulating the
      post-transcriptional step, while the transcription of the gene was inhibited by
      hyperthyroidism.

PMID- 7623782
TI  - Monoclonal antibodies that react with human band 3 residues 542-555 recognize
      different conformations of this protein in uninfected and Plasmodium falciparum
      infected erythrocytes.
AB  - A monoclonal antibody generated against synthetic peptides patterned on amino
      acids 542-555 of human band 3, designated 1F4, specifically immunostained
      Plasmodium falciparum-infected erythrocytes and inhibited the cytoadherence of P.
      falciparum-infected erythrocytes to C32 amelanotic melanoma cells. 1F4 did not
      recognize intact band 3 protein on immunoblots, however it was reactive towards
      proteolytic fragments of band 3. The binding region of another murine monoclonal
      antibody previously reported to recognize the membrane spanning domain of human
      band 3, designated B6, was found to also recognize residues 542-555, however its
      properties differed from 1F4. Mab B6 recognized both infected and uninfected red
      cells, and reacted only with intact band 3 on immunoblots. Mab B6 was without
      effect on cytoadherence. These results demonstrate that monoclonal antibodies
      reactive against a common peptide sequence may bind to different conformations of
      the peptide sequence and suggest that the adherent competency of P. falciparum
      infected erythrocytes may result from a change in the surface topography of human
      band 3 protein.

PMID- 7623783
TI  - Protective effect of spermine on DNA exposed to oxidative stress.
AB  - Pathological conditions that cause oxidative stress can affect DNA integrity. The
      aim of this research was to study the protective effect of spermine against DNA
      damage induced by an oxygen-radical generating system. Deoxyguanosine and DNA
      were separately dissolved in phosphate buffer and incubated for 1 h at 40 degrees
      C in the presence of 50 mM H2O2/10 mM ascorbic acid. Single nucleosides and their
      products of oxidation were then obtained by enzymatic digestion of DNA. The
      compounds were separated by micellar electrokinetic capillary chromatography
      (MECC) with SDS-modified mobile phase and detected at 254 nm. Two major products
      of DNA oxidation have been identified as derivatives of deoxyguanosine with
      electrophoretic properties different from 8-hydroxy-2'-deoxyguanosine. When the
      oxidation of DNA was carried out in the presence of 0.1 mM spermine, the
      formation of the two by-products of deoxyguanosine was markedly reduced. On the
      contrary, spermine did not prevent the oxidation of deoxyguanosine alone,
      suggesting that the polyamine should be bound to the DNA strands to exert its
      antioxidative effect.

PMID- 7623785
TI  - Effects of magnesium and iron on lipid peroxidation in cultured hepatocytes.
AB  - In primary cultures of rat hepatocytes, the effects of extracellular Mg2+ and Fe
      on lipid peroxidation (LPO) as measured by means of malondialdehyde (MDA)
      formation were investigated. Incubation of hepatocytes at decreasing
      extracellular Mg2+ concentration enhanced LPO, depending on extracellular Fe.
      About 96% of MDA accumulated in the culture medium. Addition of desferrioxamine
      prevented LPO. Additionally, the formation of oxygen free radicals was determined
      by fluorescence reduction of cis-parinaric acid. With this method, an immediate
      decay of fluorescence was found after addition of Fe2+. Fluorescence reduction
      was completely prevented by desferrioxamine, indicating the function of
      extracellular Fe. This mechanism may operate additionally to the increase in
      intracellular Fe and intracellular formation of oxygen free radicals during Mg
      deficiency in vivo.

PMID- 7623784
TI  - Stretch affects phenotype and proliferation of vascular smooth muscle cells.
AB  - The exertion of periodic dynamic strain on the arterial wall is hypothesized to
      be relevant to smooth muscle cell morphology and function. This study has
      investigated the effect of cyclic mechanical stretching on rabbit aortic smooth
      muscle cell proliferation and expression of contractile phenotype protein
      markers. Cells were cultured on flexible-bottomed dishes and cyclic stretch was
      applied (frequency 30 cycles/min, 15% elongation) using a Flexercell Strain unit.
      Cyclic stretch potentiated smooth muscle cell proliferation in serum-activated
      cultures but not in cultures maintained in 0.5% fetal calf serum. Stretching
      induced a serum-independent increase of h-caldesmon expression and this effect
      was reversible following termination of mechanical stimulation. Strain was
      without effect on smooth muscle myosin or calponin expression. In cells grown on
      laminin stretch-induced h-caldesmon expression was more prominent than in cells
      cultured on collagen types I and IV, poly-L-lysine and gelatin. These data
      suggest that cyclic mechanical stimulation possesses dual effect on vascular
      smooth muscle cell phenotype characteristics since it: 1) potentiates
      proliferation, an attribute of a dedifferentiated phenotype; and 2) increases
      expression of h-caldesmon considered a marker of a differentiated smooth muscle
      cell state.

PMID- 7623786
TI  - Adenosine effects upon insulin action on lipolysis and glucose transport in human
      adipocytes.
AB  - The dose response effect of a new adenosine analogue, GR79236 (N-[1S trans-2
      hydroxycyclopentyl] adenosine) upon insulin sensitivity was examined in human
      adipocytes. The influence of adenosine upon insulin sensitivity for suppression
      of lipolysis and stimulation of glucose transport was examined. Removal of
      adenosine by use of adenosine deaminase stimulated lipolysis to the same extent
      as did 10(-9) M noradrenaline. GR79236 brought about dose dependent inhibition of
      lipolysis with half-maximal effect at 11.3 +/- 7.8 x 10(-9) M. When lipolysis was
      stimulated by noradrenaline alone the subsequent inhibition of lipolysis brought
      about by GR79236 was significantly greater than that of insulin. To examine
      adenosine effects on the insulin signalling pathway separately from those on
      lipolysis, the insulin sensitivity of glucose transport was examined. Removal of
      adenosine brought about a small but significant increase in the concentration of
      insulin required for half-maximal stimulation of glucose transport. Adenosine
      agonists offer promise as new agents for the modulation of metabolism in diabetes
      and other states of insulin resistance.

PMID- 7623788
TI  - Purification of histidine-tagged ras and its use in the detection of ras binding
      proteins.
AB  - Recombinant histidine-tagged v-Ha-ras (his-ras) was purified to homogeneity from
      extracts of E. coli M15 using a one-step procedure which involved immobilised
      metal ion chromatography on Ni(2+)-nitriloacetic acid agarose (Ni-NTA). The
      optimal pH for elution by imidazole was 6.6 and the yield of his-ras protein
      (greater than 95% pure) was about 4 mg/litre E. coli culture. Chromatography of a
      mixture of purified his-ras and rat brain cytosol on Ni-NTA together with SDS
      PAGE and silver staining of proteins were employed to search for ras-binding
      proteins present in rat brain cytosol. Chromatography of rat brain cytosol alone
      on Ni-NTA revealed several protein species which were not readily eluted with
      imidazole. These are likely to be low-abundance brain metal ion binding proteins.
      Pre-treatment of rat brain cytosol with Ni-NTA before a second round of
      chromatography on Ni-NTA removed most of these proteins. Chromatography of a
      mixture of pre-treated rat brain cytosol and purified his-ras protein revealed
      four new protein bands with molecular weights of 250, 90, 80 and 70 kDa. These
      were considered to be candidate ras-binding proteins. It is concluded that the
      use of his-ras and immobilised metal ion chromatography does provide an approach
      which can be used to identify ras binding proteins present in cellular extracts.

PMID- 7623787
TI  - Protein 1a: a major wheat germ agglutinin binding protein on the surface of human
      granulocytes associated with the cytoskeleton.
AB  - Lectin-receptors on leukocyte and endothelial surfaces are becoming more
      important in the light of increasing evidence which implicates lectin
      carbohydrate interactions in diverse physiological phenomena. This study reports
      the identification of a major 118 kDa granulocyte surface protein, (Protein 1 a)
      which binds the lectin wheat germ agglutinin (WGA), and is distinctly different
      from reported WGA binding granulocyte membrane proteins. Protein 1 a has been
      isolated from the Triton-soluble and Triton-insoluble lysates of normal
      individuals and patients with Chronic Myeloid Leukemia (CML) using a combination
      of differential solubilization, lectin affinity, ion exchange chromatography and
      HPLC. The protein from the detergent lysates of both normal and CML granulocytes
      has similar pI values, lectin affinities, and hydrophobicity. However, its
      solubility in Triton is different in the two cell types. In 71% of CML cases
      examined, Protein 1 a exhibits decreased Triton solubility suggesting its
      increased association with the cytoskeleton (CSK). Stimulation of normal
      granulocytes with WGA leads to the translocation of the soluble form of Protein 1
      a to the Triton-insoluble fraction. This cytoskeletal recruitment of Protein 1 a
      is sustained only under conditions of excess WGA and occupied receptor. The CSK
      disruptive agent dihydrocytochalasin B (H2CB) releases the insoluble form of the
      receptor into the Triton-soluble fraction. Investigation of a CSK-involving
      process such as ligand internalization revealed that CML granulocytes exhibit
      slower kinetics of internalization of fluorescent WGA molecules.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7623789
TI  - Synthesis and secretion of caseins by the mouse mammary gland: production and
      characterization of new polyclonal antibodies.
AB  - Polyclonal antibodies to mouse alpha- and beta/gamma-caseins were raised in
      rabbits. These antibodies display tissue- and species specificity as shown by
      immunoblotting. Immunohistochemical analyses demonstrate that both alpha- and
      beta/gamma-caseins were synthesized and secreted from virtually all lactating
      mammary epithelial cells, in a pattern very similar to that of the mouse alpha
      lactalbumin. Residual amounts of caseins were located also in the apical surface
      of epithelial cells surrounding the ducal lumen of virgin mammary gland sections.
      In contrast to the significant level of gamma-casein in the milk, the amount of
      this protein compared to alpha- or beta-caseins was extremely low in medium
      conditioned for 24 h by mammary explants of mid-pregnant mice immediately after
      explantation or after 4 days.

PMID- 7623790
TI  - Structural, genetic and pharmacological identity of the rat alpha 2-adrenergic
      receptor subtype cA2-47 and its molecular characterization in rat adrenal,
      adrenocortical carcinoma and bovine retina.
AB  - Subsequent to the first alpha 2-adrenergic receptor (alpha 2-AR) gene cloning of
      alpha 2-C10 from human platelet, cloning of the first rodent alpha 2-AR cDNA, cA2
      47, was reported. Based on the structural and limited pharmacological comparison,
      it was concluded that the rodent receptor is a molecular and pharmacological
      analog of the human receptor, which is pharmacologically classified as the alpha
      2A-AR. A later study slightly revised the structure of the human receptor. Thus,
      the precise structural comparison of the rat receptor to the human platelet
      receptor is no longer valid. Another rat alpha 2-AR gene, RG20, was then cloned
      and was also found to be a structural analog of the human alpha 2-C10. It,
      however, varied slightly from the alpha 2A subtype pharmacology, but matched the
      newly defined alpha 2D subtype pharmacology. It was, therefore, concluded that
      RG20 encodes the alpha 2D subtype. The structural and pharmacological
      relationship of RG20 with cA2-47 is not known, although it has been tacitly
      assumed that both are the identical alpha 2D receptor subtypes. The present study
      addresses this and other issues relating to the precise structural, genetic and
      pharmacological relationship of cA2-47 with the human platelet alpha 2-C10
      receptor, and also the localization of cA2-47 transcript in certain rat tissues.
      The results show that the cA2-47 receptor shows a high degree of sequence
      identity to the alpha 2-C10 receptor, yet important differences exist between
      them. The sequence identity of cA2-47 receptor to the RG20 receptor is almost,
      but not quite complete. The cA2-47 gene is not present in the human and the human
      gene is not present in the rat; that cA2-47 receptor subtype is pharmacologically
      similar to the RG20 receptor subtype, both being of the alpha 2D subtype. The cA2
      47 receptor transcript in addition to being found in the rat brain is present in
      the rat adrenal gland, testes, adrenocortical carcinoma and the bovine retina.

PMID- 7623791
TI  - A macrolide antibiotic, roxithromycin, inhibits the growth of human myeloid
      leukemia HL60 cells by producing multinucleate cells.
AB  - The antiproliferative effect of roxithromycin (RXM) was studied using human
      myeloid leukemia HL60 cells. RXM inhibited the growth of HL60 cells in a
      concentration-dependent manner, and significantly inhibited growth at
      concentrations above 75 microM. This growth inhibition was not associated with
      specific cell cycle arrest and DNA synthesis was not impaired. In addition, the
      number of viable cells remained almost unchanged in the presence of 100 microM
      RXM. RXM induced growth inhibition at least partly by the formation of
      multinucleate cells. Both flowcytometric and morphological examination revealed
      that more than 40% of the RXM-treated cells were binucleate. These findings
      demonstrate that RXM is a potent new modulator of cell cycle progression in HL60
      cells and suggest that the inhibition of cytokinesis by this drug may provide a
      new model for studying mitosis.

PMID- 7623792
TI  - Kinetic properties of hexose-monophosphate dehydrogenases. II. Isolation and
      partial purification of 6-phosphogluconate dehydrogenase from rat liver and
      kidney cortex.
AB  - 6-Phosphogluconate dehydrogenase (6PGDH) from rat-liver and kidney-cortex cytosol
      has been partially purified and almost completely isolated (more than 95%) from
      glucose-6-phosphate dehydrogenase activity. The purification and isolation
      procedures included high-speed centrifugation, 60-75% ammonium-sulphate
      fractionation, by which both hexose-monophosphate dehydrogenases activities were
      separated, and finally the protein fraction was applied to a chromatographic
      column of Sephadex G-25 equilibrated with 10 mM Tris-EDTA-NADP buffer, pH 7.6, to
      eliminate any contaminating metabolites. The kinetic properties of the isolated
      partially purified liver and renal 6PGDH were examined. The saturation curves of
      this enzyme in both rat tissues showed a typical Michaelis-Menten kinetic, with
      no evidence of co-operativity. The optimum pH for both liver and kidney-cortex
      6PGDH was 8.0. The Km values of liver 6PGDH for 6-phosphogluconate (6PG) and for
      NADP were 157 microM and 258 microM respectively, while the specific activity
      measured at optimum conditions (pH 8.0 and 37 degrees C) was 424.2 mU/mg of
      protein. NADPH caused a competitive inhibition against NADP with an inhibition
      constant (Ki) of 21 microM. The Km values for 6PG and NADP from kidney-cortex
      6PGDH were 49 microM and 56 microM respectively. The specific activity at pH 8.0
      and 37 degrees C was 120.7 mU/mg of protein. NADPH also competitively inhibited
      6PGDH activity, with a Ki of 41 microM. This paper describes a quick, easy and
      reliable method for the separation of the two dehydrogenases present in the
      oxidative segment of the pentose-phosphate pathway in animal tissues, eliminating
      interference in the measurements of their activities.

PMID- 7623793
TI  - Established epigenetic modifications determine the expression of developmentally
      regulated globin genes in somatic cell hybrids.
AB  - Somatic cell hybrids generated from transgenic mouse cells have been used to
      examine the developmental regulation of human gamma-to-beta-globin gene
      switching. In hybrids between mouse erythroleukemia (MEL) cells and transgenic
      erythroblasts taken at various stages of development, there was regulated
      expression of the human fetal gamma and adult beta genes, reproducing the in vivo
      pattern prior to fusion. Hybrids formed from embryonic blood cells produced
      predominantly gamma mRNA, whereas beta gene expression was observed in adult
      hybrids and a complete range of intermediate patterns was found in fetal liver
      hybrids. The adult environment of the MEL cells, therefore, did not appear to
      influence selective transcription from this gene complex. Irradiation of the
      embryonic erythroid cells prior to fusion resulted in hybrids containing only
      small fragments of donor chromosomes, but the pattern of gene expression did not
      differ from that of unirradiated hybrids. This finding suggests that continued
      expression of trans-acting factors from the donor erythroblasts is not necessary
      for continued expression of the human gamma gene in MEL cells. These results
      contrast with the lack of developmental regulation of the cluster after
      transfection of naked DNA into MEL cells and suggest that epigenetic processes
      established during normal development result in the gene cluster adopting a
      developmental stage-specific, stable conformation which is maintained through
      multiple rounds of replication and transcription in the MEL cell hybrids. On
      prolonged culture, hybrids that initially expressed only the gamma transgene
      switched to beta gene expression. The time period of switching, from
      approximately 10 to > 40 weeks, was similar to that seen previously in human
      fetal erythroblast x MEL cell hybrids but in this case bore no relationship to
      the time of in vivo switching. It seems unlikely, therefore, that switching in
      these hybrids is regulated by a developmental clock.

PMID- 7623794
TI  - A 32-nucleotide exon-splicing enhancer regulates usage of competing 5' splice
      sites in a differential internal exon.
AB  - Large alternatively spliced internal exons are uncommon in vertebrate genes, and
      the mechanisms governing their usage are unknown. In this report, we examined
      alternative splicing of a 1-kb internal exon from the human caldesmon gene
      containing two regulated 5' splice sites that are 687 nucleotides apart. In cell
      lines normally splicing caldesmon RNA via utilization of the exon-internal 5'
      splice site, inclusion of the differential exon required a long purine-rich
      sequence located between the two competing 5' splice sites. This element
      consisted of four identical 32-nucleotide purine-rich repeats that resemble exon
      splicing enhancers (ESE) identified in other genes. One 32-nucleotide repeat
      supported exon inclusion, repressed usage of the terminal 5' splice site, and
      functioned in a heterologous exon dependent on exon enhancers for inclusion,
      indicating that the caldesmon purine-rich sequence can be classified as an ESE.
      The ESE was required for utilization of the internal 5' splice site only in the
      presence of the competing 5' splice site and had no effect when placed downstream
      of the terminal 5' splice site. In the absence of the internal 5' splice site,
      the ESE activated a normally silent cryptic 5' splice site near the natural
      internal 5' splice site, indicating that the ESE stimulates upstream 5' splice
      site selection. We propose that the caldesmon ESE functions to regulate
      competition between two 5' splice sites within a differential internal exon.

PMID- 7623795
TI  - Cooperative interactions between HOX and PBX proteins mediated by a conserved
      peptide motif.
AB  - Homeoprotein products of the Hox/HOM gene family pattern the animal embryo
      through the transcriptional regulation of target genes. We have previously shown
      that the labial group protein HOXA-1 has intrinsically weak DNA-binding activity
      due to residues in the N-terminal arm of its homeodomain (M. L. Phelan, R.
      Sadoul, and M. S. Featherstone, Mol. Cell. Biol. 14:5066-5075, 1994). This
      observation, among others, suggests that HOX and HOM proteins require cofactors
      for stable interactions with DNA. We have demonstrated that a putative HOX
      cofactor, PBX1A, participates in cooperative DNA binding with HOXA-1 and the
      Deformed group protein HOXD-4. Three Abdominal-B class HOX proteins failed to
      cooperate with PBX1A. We mapped the interacting domain of HOXD-4 to the YPWMK
      pentapeptide motif, a conserved sequence found N terminal to the homeodomain of
      HOXA-1 and many other homeoproteins but absent from the Abdominal-B class. The
      naturally occurring fusion of the transcriptional activation domain of E2A with
      PBX1 creates an oncoprotein implicated in human pre-B-cell leukemias (M. P.
      Kamps, C. Murre, X.-H. Sun, and D. Baltimore, Cell 60:547-555, 1990; J. Nourse,
      J. D. Mellentin, N. Galili, J. Wilkinson, E. Starbridge, S. D. Smith, and M. L.
      Cleary, Cell 60:535-545, 1990). A pentapeptide mutation that abolished
      cooperative interaction with PBX1A in vitro also abrogated synergistic
      transcriptional activation with the E2A/PBX oncoprotein. The direct contact of
      PBX family members by the HOX pentapeptide is likely to play an important role in
      developmental and oncogenic processes.

PMID- 7623796
TI  - The essential helicase gene RAD3 suppresses short-sequence recombination in
      Saccharomyces cerevisiae.
AB  - We have isolated an allele of the essential DNA repair and transcription gene
      RAD3 that relaxes the restriction against recombination between short DNA
      sequences in Saccharomyces cerevisiae. Double-strand break repair and gene
      replacement events requiring recombination between short identical or mismatched
      sequences were stimulated in the rad3-G595R mutant cells. We also observed an
      increase in the physical stability of double-strand breaks in the rad3-G595R
      mutant cells. These results suggest that the RAD3 gene suppresses recombination
      involving short homologous sequences by promoting the degradation of the ends of
      broken DNA molecules.

PMID- 7623797
TI  - CENP-B binds a novel centromeric sequence in the Asian mouse Mus caroli.
AB  - Minor satellite DNA, found at Mus musculus centromeres, is not present in the
      genome of the Asian mouse Mus caroli. This repetitive sequence family is
      speculated to have a role in centromere function by providing an array of binding
      sites for the centromere-associated protein CENP-B. The apparent absence of CENP
      B binding sites in the M. caroli genome poses a major challenge to this
      hypothesis. Here we describe two abundant satellite DNA sequences present at M.
      caroli centromeres. These satellites are organized as tandem repeat arrays, over
      1 Mb in size, of either 60- or 79-bp monomers. All autosomes carry both
      satellites and small amounts of a sequence related to the M. musculus major
      satellite. The Y chromosome contains small amounts of both major satellite and
      the 60-bp satellite, whereas the X chromosome carries only major satellite
      sequences. M. caroli chromosomes segregate in M. caroli x M. musculus
      interspecific hybrid cell lines, indicating that the two sets of chromosomes can
      interact with the same mitotic spindle. Using a polyclonal CENP-B antiserum, we
      demonstrate that M. caroli centromeres can bind murine CENP-B in such an
      interspecific cell line, despite the absence of canonical 17-bp CENP-B binding
      sites in the M. caroli genome. Sequence analysis of the 79-bp M. caroli satellite
      reveals a 17-bp motif that contains all nine bases previously shown to be
      necessary for in vitro binding of CENP-B. This M. caroli motif binds CENP-B from
      HeLa cell nuclear extract in vitro, as indicated by gel mobility shift analysis.
      We therefore suggest that this motif also causes CENP-B to associate with M.
      caroli centromeres in vivo. Despite the sequence differences, M. caroli presents
      a third, novel mammalian centromeric sequence producing an array of binding sites
      for CENP-B.

PMID- 7623798
TI  - Detection of leucine-independent DNA site occupancy of the yeast Leu3p
      transcriptional activator in vivo.
AB  - The product of the Saccharomyces cerevisiae LEU3 gene, Leu3p, is a
      transcriptional activator which regulates leucine biosynthesis in response to
      intracellular levels of leucine through the biosynthetic intermediate alpha
      isopropylmalate. We devised a novel assay to examine the DNA site occupancy of
      Leu3p under different growth conditions, using a reporter gene with internal
      Leu3p-binding sites. Expression of the reporter is inhibited by binding of
      nuclear Leu3p to these sites; inhibition is dependent on the presence of the
      sites in the reporter, on the integrity of the Leu3p DNA-binding domain, and,
      surprisingly, on the presence of a transcriptional activation domain in the
      inhibiting protein. By this assay, Leu3p was found to occupy its binding site
      under all conditions tested, including high and low levels of leucine and in the
      presence and absence of alpha-isopropylmalate. The localization of Leu3p to the
      nucleus was confirmed by immunofluorescence staining of cells expressing epitope
      tagged Leu3p derivatives. We conclude that Leu3p regulates transcription in vivo
      without changing its intracellular localization and DNA site occupancy.

PMID- 7623799
TI  - A link between increased transforming activity of lymphoma-derived MYC mutant
      alleles, their defective regulation by p107, and altered phosphorylation of the c
      Myc transactivation domain.
AB  - The c-Myc protein is a transcription factor with an N-terminal transcriptional
      regulatory domain and C-terminal oligomerization and DNA-binding motifs. Previous
      studies have demonstrated that p107, a protein related to the retinoblastoma
      protein, binds to the c-Myc transcriptional activation domain and suppresses its
      activity. We sought to characterize the transforming activity and transcriptional
      properties of lymphoma-derived mutant MYC alleles. Alleles encoding c-Myc
      proteins with missense mutations in the transcriptional regulatory domain were
      more potent than wild-type c-Myc in transforming rodent fibroblasts. Although the
      mutant c-Myc proteins retained their binding to p107 in in vitro and in vivo
      assays, p107 failed to suppress their transcriptional activation activities. Many
      of the lymphoma-derived MYC alleles contain missense mutations that result in
      substitution for the threonine at codon 58 or affect sequences flanking this
      amino acid. We observed that in vivo phosphorylation of Thr-58 was absent in a
      lymphoma cell line with a mutant MYC allele containing a missense mutation
      flanking codon 58. Our in vitro studies suggest that phosphorylation of Thr-58 in
      wild-type c-Myc was dependent on cyclin A and required prior phosphorylation of
      Ser-62 by a p107-cyclin A-CDK complex. In contrast, Thr-58 remained
      unphosphorylated in two representative mutant c-Myc transactivation domains in
      vitro. Our studies suggest that missense mutations in MYC may be selected for
      during lymphomagenesis, because the mutant MYC proteins have altered functional
      interactions with p107 protein complexes and fail to be phosphorylated at Thr-58.

PMID- 7623800
TI  - Positive autoregulation of the yeast transcription factor Pdr3p, which is
      involved in control of drug resistance.
AB  - Simultaneous resistance to an array of drugs with different cytotoxic activities
      is a property of Saccharomyces cerevisiae, in which the protein Pdr3p has
      recently been shown to play a role as a transcriptional regulator. We provide
      evidence that the yeast PDR3 gene, which encodes a zinc finger transcription
      factor implicated in certain drug resistance phenomena, is under positive
      autoregulation by Pdr3p. DNase I footprinting analyses using bacterially
      expressed Pdr3p showed specific recognition by this protein of at least two
      upstream activating sequences in the PDR3 promoter. The use of lacZ reporter
      constructs, a mutational analysis of the upstream activating sequences, as well
      as band shift experiments enabled the identification of two 5'TC CGCGGA3'
      sequence motifs in the PDR3 gene as consensus elements for the binding of Pdr3p.
      Several similar sequence motifs can be found in the promoter of PDR5, a gene
      encoding an ATP-dependent drug pump whose Pdr3p-induced overexpression is
      responsible for drug resistance phenomena. Recently one of these sequence
      elements was shown to be the target of Pdr3p to elevate the level of PDR5
      transcription. Finally, we provide evidence in the absence of PDR1 for a PDR3
      controlled transcriptional induction of the drug pump by cycloheximide and
      propose a model for the mechanism governing the transcriptional autoregulation of
      Pdr3p.

PMID- 7623801
TI  - The miti-mere and pdm1 genes collaborate during specification of the RP2/sib
      lineage in Drosophila neurogenesis.
AB  - We have investigated (i) the role of pdm1, a Drosophila POU gene, during the
      elaboration of the GMC-1-->RP2/sib lineage and (ii) the functional relationship
      between pdm1 and the closely linked second POU gene, miti-mere, in this lineage.
      We show that deletion of pdm1 causes a partially penetrant GMC-1 defect, while
      deletion of both miti and pdm1 results in a fully penetrant defect. This GMC-1
      defect in miti- and pdm1- embryos can be rescued by the pdm1 or miti transgene.
      Rescue is observed only when these genes are expressed at the time of GMC-1
      formation. Overexpression of pdm1 or miti well after GMC-1 is formed results in
      the duplication of RP2 and/or sib cells. Our results indicate that both genes are
      required for the normal development of this lineage and that the two collaborate
      during the specification of GMC-1 identity.

PMID- 7623802
TI  - Nucleolar localization of parathyroid hormone-related peptide enhances survival
      of chondrocytes under conditions that promote apoptotic cell death.
AB  - Parathyroid hormone-related peptide (PTHrP) is a mediator of cellular growth and
      differentiation as well as a cause of malignancy-induced hypercalcemia. Most of
      the actions of PTHrP have been attributed to its interaction with a specific cell
      surface receptor that binds the N-terminal domain of the protein. Here we present
      evidence that PTHrP promotes some of its cellular effects by translocating to the
      nucleolus. Localization of transiently expressed PTHrP to the nucleolus was
      dependent on the presence of a highly basic region at the carboxyl terminus of
      the molecule that bears homology to nucleolar targeting sequences identified
      within human retroviral (human immunodeficiency virus type 1 and human T-cell
      leukemia virus type 1) regulatory proteins. Endogenous PTHrP also localized to
      the nucleolus in osseous cells in vitro and in vivo. Moreover, expression of
      PTHrP in chondrocytic cells (CFK2) delayed apoptosis induced by serum
      deprivation, and this effect depended on the presence of an intact nucleolar
      targeting signal. The present findings demonstrate a unique intracellular mode of
      PTHrP action and a novel mechanism by which this peptide growth factor may
      modulate programmed cell death.

PMID- 7623803
TI  - DNA binding specificity determinants in MADS-box transcription factors.
AB  - The MADS box is a conserved sequence motif found in the DNA binding domain of a
      family of transcription factors which possess related but distinct DNA binding
      specificities. We investigated the basis of differential sequence recognition by
      the MADS-box proteins serum response factor (SRF), MCM1, and MEF2A, using
      chimeric proteins and site-directed mutants in conjunction with gel mobility
      shift and binding site selection assays. Deletion of sequences immediately N
      terminal to the SRF MADS box alters its preferred binding site to that of MEF2A,
      although the resulting protein still weakly binds SRF-specific sites: exclusive
      binding to MEF2 sites requires further mutations, at MADS-box residues 11 to 15.
      In contrast to SRF, the sequence specificity of MCM1 (and of MEF2A) is determined
      entirely by sequences within its MADS box, and mutation of only SRF MADS-box
      residue 1 is sufficient to alter its binding specificity to that of MCM1.
      However, changes at both MADS-box positions 1 and 11 to 15 are necessary and
      sufficient to alter the specificity of the MCM1 MADS box to that of MEF2, and
      vice versa. The role of SRF MADS-box residues which differ from those present in
      the other proteins was investigated by selection of functional SRF variants in
      yeast cells. SRF MADS-box position 1 was always a glycine in the variants, but
      many different sequences at the other nonconserved MADS-box residues were
      compatible with efficient DNA binding. We discuss potential mechanisms of DNA
      recognition by MADS-box proteins.

PMID- 7623804
TI  - Synthetic signals for ubiquitin-dependent proteolysis.
AB  - Short-lived proteins are targeted for turnover by sequence elements known as
      degradation signals. Because of the large size and heterogeneity of these
      signals, the structural features important for their function are not well
      defined. In this study, we have isolated three classes of degradation signals by
      screening short artificial sequences for the ability to destabilize a reporter
      protein. Class I and class II signals were derived by inserting random
      nonapeptide sequences after the second residue of beta-galactosidase. Class III
      signals contained five-residue homopolymers at the same position. Class I beta
      galactosidase turnover was inhibited in mutants lacking either the ubiquitin
      conjugating enzyme Ubc2 or the ubiquitin protein ligase Ubr1. Class I random
      inserts functioned to promote N-terminal proteolytic processing and define a
      novel pathway for exposure of residues that are destabilizing according to the N
      end rule. Efficient degradation of proteins containing class II signals required
      at least three Ubc enzymes: Ubc6, Ubc7, and either one of the related enzymes
      Ubc4 and Ubc5. Analysis of 56 amino acid substitutions in the class II signal
      suggested that it is recognized in the form of an amphipathic alpha helix. Class
      III signals consisted of short tracts of hydrophobic residues such as Leu and
      Ile. Degradation of class III proteins involved the Ubc4 and Ubc5 enzymes but not
      Ubc2, Ubc6, or Ubc7. Clusters of hydrophobic residues appear to be critical for
      the recognition of both class II and class III signals.

PMID- 7623806
TI  - Cloning, functional characterization, and mechanism of action of the B-cell
      specific transcriptional coactivator OCA-B.
AB  - Biochemical purification and cognate cDNA cloning studies have revealed that the
      previously described transcriptional coactivator OCA-B consists of a 34- or 35
      kDa polypeptide with sequence relationships to known coactivators that function
      by protein-protein interactions. Studies with a recombinant protein have proved
      that a single OCA-B polypeptide is the main determinant for B-cell-specific
      activation of immunoglobulin (Ig) promoters and provided additional insights into
      its mechanism of action. Recombinant OCA-B can function equally well with Oct-1
      or Oct-2 on an Ig promoter, but while corresponding POU domains are sufficient
      for OCA-B interaction, and for octamer-mediated transcription of a histone H2B
      promoter, an additional Oct-1 or Oct-2 activation domain(s) is necessary for
      functional synergy with OCA-B. Further studies additional Oct-1 or Oct-2
      activation domain(s) is necessary for functional synergy with OCA-B. Further
      studies show that Ig promoter activation by Oct-1 and OCA-B requires still other
      general (USA-derived) cofactors and also provide indirect evidence that distinct
      Oct-interacting cofactors regulate H2B transcription.

PMID- 7623805
TI  - Inhibition of transcription factor GATA-4 expression blocks in vitro cardiac
      muscle differentiation.
AB  - Commitment of mesodermal cells to the cardiac lineage is a very early event that
      occurs during gastrulation, and differentiation of cardiac muscle cells begins in
      the presomite stage prior to formation of the beating heart tube. However, the
      molecular events, including gene products that are required for differentiation
      of cardiac muscle cells, remain essentially unknown. GATA-4 is a recently
      characterized cardiac muscle-restricted transcription factor whose properties
      suggest an important regulatory role in heart development. We tested the role of
      GATA-4 in cardiac differentiation, using the pluripotent P19 embryonal carcinoma
      cells, which can be differentiated into beating cardiac muscle cells. In this
      system, GATA-4 transcripts and protein are restricted to cells committed to the
      cardiac lineage, and induction of GATA-4 precedes expression of cardiac marker
      genes and appearance of beating cells. Inhibition of GATA-4 expression by
      antisense transcripts blocks development of beating cardiac muscle cells and
      interferes with expression of cardiac muscle markers. These data indicate that
      GATA-4 is necessary for development of cardiac muscle cells and identify for the
      first time a tissue-specific transcription factor that may be crucial for early
      steps of mammalian cardiogenesis.

PMID- 7623807
TI  - Regulation of Raf-1 and Raf-1 mutants by Ras-dependent and Ras-independent
      mechanisms in vitro.
AB  - The serine/threonine kinase Raf-1 functions downstream from Ras to activate
      mitogen-activated protein kinase kinase, but the mechanisms of Raf-1 activation
      are incompletely understood. To dissect these mechanisms, wild-type and mutant
      Raf-1 proteins were studied in an in vitro system with purified plasma membranes
      from v-Ras- and v-Src-transformed cells (transformed membranes). Wild-type (His)6
      and FLAG-Raf-1 were activated in a Ras- and ATP-dependent manner by transformed
      membranes; however, Raf-1 proteins that are kinase defective (K375M), that lack
      an in vivo site(s) of regulatory tyrosine (YY340/341FF) or constitutive serine
      (S621A) phosphorylation, that do not bind Ras (R89L), or that lack an intact zinc
      finger (CC165/168SS) were not. Raf-1 proteins lacking putative regulatory sites
      for an unidentified kinase (S259A) or protein kinase C (S499A) were activated but
      with apparently reduced efficiency. The kinase(s) responsible for activation by
      Ras or Src may reside in the plasma membrane, since GTP loading of plasma
      membranes from quiescent NIH 3T3 cells (parental membranes) induced de novo
      capacity to activate Raf-1. Wild-type Raf-1, possessing only basal activity, was
      not activated by parental membranes in the absence of GTP loading. In contrast,
      Raf-1 Y340D, possessing significant activity, was, surprisingly, stimulated by
      parental membranes in a Ras-independent manner. The results suggest that
      activation of Raf-1 by phosphorylation may be permissive for further modulation
      by another membrane factor, such as a lipid. A factor(s) extracted with methanol
      chloroform from transformed membranes or membranes from Sf9 cells coexpressing
      Ras and SrcY527F significantly enhanced the activity of Raf-1 Y340D or active Raf
      1 but not that of inactive Raf-1. Our findings suggest a model for activation of
      Raf-1, wherein (i) Raf-1 associates with Ras-GTP, (ii) Raf-1 is activated by
      tyrosine and/or serine phosphorylation, and (iii) Raf-1 activity is further
      increased by a membrane cofactor.

PMID- 7623809
TI  - Activation of the high-affinity immunoglobulin E receptor Fc epsilon RI in RBL
      2H3 cells is inhibited by Syk SH2 domains.
AB  - Antigen-mediated aggregation of the high-affinity receptor for immunoglobulin E,
      Fc epsilon RI, results in the activation of multiple signaling pathways, leading
      to the release of mediators of the allergic response. One of the earliest
      responses to receptor stimulation is the tyrosine phosphorylation of the beta and
      gamma subunits of Fc epsilon RI and the association of the tyrosine kinase Syk
      with the phosphorylated receptor. This association is mediated by the SH2 domains
      of Syk and is believed to be critical for activating signaling pathways resulting
      in mediator release. To examine the importance of the interaction of Syk with Fc
      epsilon RI in signaling events following receptor activation, we introduced a
      protein containing the SH2 domains of Syk into streptolysin O-permeabilized RBL
      2H3 cells. The Syk SH2 domains completely inhibited degranulation and leukotriene
      production following receptor aggregation, and they blocked the increase in
      protein tyrosine phosphorylation observed after receptor activation. Inhibition
      was specific for Fc epsilon RI-mediated signaling, since degranulation of cells
      activated by alternative stimuli was not blocked by the Syk SH2 domains. A
      protein containing a point mutation in the carboxy-terminal SH2 domain which
      abolishes phosphotyrosine binding was not inhibitory. In addition, inhibition of
      degranulation was reversed by pretreatment of the SH2 domains with a tyrosine
      phosphorylated peptide corresponding to the tyrosine-based activation motif found
      in the gamma subunit of Fc epsilon RI, the nonphosphorylated peptide had no
      effect. The association of Syk with the tyrosine-phosphorylated gamma subunit of
      the activated receptor was blocked by the Syk SH2 domains, and deregulation in
      cells activated by clustering of Syk directly without Fc epsilon RI aggregation
      was not affected by the Syk SH2 domains. These results demonstrate that the
      association of Syk with the activated Fc epsilon RI is critical for both early
      and late events following receptor activation and confirm the key role Syk plays
      in signaling through the high-affinity IgE receptor.

PMID- 7623811
TI  - Yeast mRNA cap methyltransferase is a 50-kilodalton protein encoded by an
      essential gene.
AB  - RNA (guanine-7-)methyltransferase, the enzyme responsible for methylating the 5'
      cap structure of eukaryotic mRNA, was isolated from extracts of Saccharomyces
      cerevisiae. The yeast enzyme catalyzed methyl group transfer from S-adenosyl-L
      methionine to the guanosine base of capped, unmethylated poly(A). Cap methylation
      was stimulated by low concentrations of salt and was inhibited by S-adenosyl-L
      homocysteine, a presumptive product of the reaction, but not by S-adenosyl-D
      homocysteine. The methyltransferase sedimented in a glycerol gradient as a single
      discrete component of 3.2S. A likely candidate for the gene encoding yeast cap
      methyltransferase was singled out on phylogenetic grounds. The ABD1 gene, located
      on yeast chromosome II, encodes a 436-amino-acid (50-kDa) polypeptide that
      displays regional similarity to the catalytic domain of the vaccinia virus cap
      methyltransferase. That the ABD1 gene product is indeed RNA (guanine-7
      )methyltransferase was established by expressing the ABD1 protein in bacteria,
      purifying the protein to homogeneity, and characterizing the cap
      methyltransferase activity intrinsic to recombinant ABD1. The physical and
      biochemical properties of recombinant ABD1 methyltransferase were
      indistinguishable from those of the cap methyltransferase isolated and partially
      purified from whole-cell yeast extracts. Our finding that the ABD1 gene is
      required for yeast growth provides the first genetic evidence that a cap
      methyltransferase (and, by inference, the cap methyl group) plays an essential
      role in cellular function in vivo.

PMID- 7623810
TI  - A nuclear factor (NF2d9) that binds to the male-specific P450 (Cyp 2d-9) gene in
      mouse liver.
AB  - Expression of the Cyp 2d-9 (steroid 16 alpha-hydroxylase) gene in mouse liver is
      male specific in such Mus musculus domesticus strains as FVB/N, whereas the
      corresponding P450 genes in the wild mouse species Mus spretus are not sex
      specific in their expression. These parental differences in the gene expressions
      were independently inherited in F1 offspring from crosses of FVB/N and M.
      spretus. A 5' flanking sequence (-110CTC CTCCCTATTCCGGGCC-92) was defined as a
      regulatory element (named SDI-A1) for the domestic Cyp 2d-9 promoter. The
      nucleotide which corresponds to T at position -99 within SDI-A1 was found to be
      substituted with C in the wild mouse P450 genes. The placing of C at position -99
      abolished the transcriptional activity of SDI-A1 in HepG2 cells as well as the
      binding of SDI-A1 to a nuclear factor. This factor (designated NF2d9) was
      purified from mouse nuclear extracts, and its cDNA cloned. The purified NF2d9
      bound to SDI-A1 but not to the mutated SDI-A1 with C at position -99. The deduced
      amino acid sequence revealed that NF2d9 is 72 and 94% identical to mouse CP2 and
      human LBP-1a, respectively. NF2d9 thus belongs to the CP2 family and is the mouse
      homolog of human LBP-1a, which modulates human immunodeficiency virus type 1
      transcription. Anti-NF2d9, which was raised against the bacterially expressed
      protein, supershifted the SDI-A1 complex with the liver nuclear extract. Both the
      bacterially expressed and in vitro-translated NF2d9 inhibited SDI-A1 complex
      formation, although they did not bind to SDI-A1 directly. The results, therefore,
      indicate that the domestic Cyp 2d-9 gene can be regulated through a specific
      association of NF2d9 with SDI-A1.

PMID- 7623808
TI  - Identification of an origin of bidirectional DNA replication in the ubiquitously
      expressed mammalian CAD gene.
AB  - Most DNA replication origins in eukaryotes localize to nontranscribed regions,
      and there are no reports of origins within constitutively expressed genes. This
      observation has led to the proposal that there may be an incompatibility between
      origin function and location within a ubiquitously expressed gene. The
      biochemical and functional evidence presented here demonstrates that an origin of
      bidirectional replication (OBR) resides within the constitutively expressed
      housekeeping gene CAD, which encodes the first three reactions of de novo uridine
      biosynthesis (carbamoyl-phosphate synthetase, aspartate carbamoyltransferase, and
      dihydroorotase). The OBR was localized to a 5-kb region near the center of the
      Syrian hamster CAD transcriptional unit. DNA replication initiates within this
      region in the single-copy CAD gene in Syrian baby hamster kidney cells and in the
      large chromosomal amplicons that were generated after selection with N
      phosphonacetyl-L-aspartate, a specific inhibitor of CAD. DNA synthesis also
      initiates within this OBR in autonomously replicating extrachromosomal amplicons
      (CAD episomes) located in an N-phosphonacetyl-L-aspartate-resistant clone (5P20)
      of CHOK1 cells. CAD episomes consist entirely of a multimer of Syrian hamster CAD
      cosmid sequences (cCAD1). These data limit the functional unit of replication
      initiation and timing control to the 42 kb of Syrian hamster sequences contained
      in cCAD1. In addition, the data indicate that the origin recognition machinery is
      conserved across species, since the same OBR region functions in both Syrian and
      Chinese hamster cells. Importantly, while cCAD1 exhibits characteristics of a
      complete replicon, we have not detected autonomous replication directly following
      transfection. Since the CAD episome was generated after excision of chromosomally
      integrated transfected cCAD1 sequences, we propose that prior localization within
      a chromosome may be necessary to "license" some biochemically defined OBRs to
      render them functional.

PMID- 7623812
TI  - Regulation of Id1 and its association with basic helix-loop-helix proteins during
      nerve growth factor-induced differentiation of PC12 cells.
AB  - Cell differentiation in the nervous system is dictated by specific patterns of
      gene expression. We have investigated the role of helix-loop-helix (HLH) proteins
      during differentiation of PC12 pheochromocytoma cells in response to nerve growth
      factor. Gel mobility shift assays using PC12 cell nuclear extracts demonstrated
      that active basic HLH complexes exist throughout differentiation. Addition of
      exogeneous Id1 protein, a negative regulator of basic HLH proteins, disrupted
      specific complexes formed by PC12 cell nuclear extracts on a CANNTG consensus
      oligonucleotide. To identify possible novel basic HLH proteins in these
      complexes, a glutathione S-transferase-Id1 fusion protein was used to screen a
      PC12 cell cDNA expression library. A single clone representing the rat E2-2 gene
      was identified. Sequential immunoprecipitations with antibodies to each HLH
      protein revealed an association between Id1 and E2-2 that could be detected in
      both untreated and nerve growth factor-treated PC12 cell lysates. These
      experiments define a new HLH interaction between Id1 and E2-2 in neuronal cells
      and suggest that neuronal differentiation may be regulated by HLH proteins in a
      distinctive manner.

PMID- 7623813
TI  - Cloning and characterization of a novel erythroid cell-derived CNC family
      transcription factor heterodimerizing with the small Maf family proteins.
AB  - The chicken beta-globin enhancer is critical for the tissue- and developmental
      stage-specific expression of the beta-globin genes. This enhancer contains two
      indispensable cis elements, one containing two GATA sites and the other
      containing an NF-E2 site. To identify the putative transcription factor acting
      through the NF-E2 motif in the chicken beta-globin enhancer, we screened chicken
      cDNA libraries with a mouse p45 NF-E2 cDNA probe and isolated cDNA clones which
      encode a protein of 582 amino acid residues. This protein contains a region that
      includes the basic region-leucine zipper domain which is well conserved among
      members of the CNC family proteins (Cap 'n' collar, p45 NF-E2, LCR-F1, Nrf1, and
      Nrf2). Hence, we named this protein ECH (erythroid cell-derived protein with CNC
      homology). ECH is expressed abundantly in cultured erythroid cells undergoing
      terminal differentiation, peripheral erythrocytes, and some nonhematopoietic
      tissues. Since most of the cDNA clones obtained from the chicken erythrocyte cDNA
      library encoded ECH, ECH is likely the predominant CNC family protein present in
      avian peripheral erythrocytes. Like p45 NF-E2, ECH can heterodimerize with any of
      the small Maf family proteins and bind the NF-E2 site as a heterodimer in vitro.
      In a transfection assay, ECH transactivates transcription depending on the
      presence of NF-E2 sites on the reporter gene plasmid. These results indicate that
      ECH is likely a key regulator of avian erythropoiesis.

PMID- 7623814
TI  - A retinoic acid response element that overlaps an estrogen response element
      mediates multihormonal sensitivity in transcriptional activation of the
      lactoferrin gene.
AB  - The lactoferrin gene is highly expressed in many different tissues, and its
      expression is controlled by different regulators. In this report, we have defined
      a retinoic acid response element (RARE) in the 5'-flanking region of the
      lactoferrin gene promoter. The lactoferrin-RARE is composed of two AGGTCA-like
      motifs arranged as a direct repeat with 1-bp spacing (DR-1). A gel retardation
      assay demonstrated that it bound strongly with retinoid X receptor (RXR)
      homodimers and RXR-retinoic acid receptor (RAR) heterodimers as well as chicken
      ovalbumin upstream promoter transcription factor (COUP-TF) orphan receptor. In CV
      1 cells, the lactoferrin-RARE linked with a heterologous thymidine kinase
      promoter was strongly activated by RXR homodimers in response to 9-cis-retinoic
      acid (9-cis-RA) but not to all-trans-RA. When the COUP-TF orphan receptor was
      cotransfected, the 9-cis-RA-induced RXR homodimer activity was strongly
      repressed. A unique feature of the lactoferrin-RARE is that it has an AGGTCA-like
      motif in common with an estrogen-responsive element (ERE). The composite RARE/ERE
      contributes to the functional interaction between retinoid receptors and the
      estrogen receptor (ER) and their ligands. In CV-1 cells, cotransfection of the
      retinoid and estrogen receptors led to mutual inhibition of the other's activity,
      while an RA-dependent inhibition of ER activity was observed in breast cancer
      cells. Furthermore, the lactoferrin-RARE/ERE showed differential transactivation
      activity in different cell types. RAs could activate the lactoferrin-RARE/ERE in
      human leukemia HL-60 cells and U937 cells but not in human breast cancer cells.
      By gel retardation analyses, we demonstrated that strong binding of the
      endogenous COUP-TF in breast cancer cells to the composite element contributed to
      diminished RA response in these cells. Thus, the lactoferrin-RARE/ERE functions
      as a signaling switch module that mediates multihormonal responsiveness in the
      regulation of lactoferrin gene expression.

PMID- 7623815
TI  - Ligand-induced association of the type I interferon receptor components.
AB  - Two transmembrane polypeptides, IFNAR and IFN-alpha/Beta R, were previously
      identified as essential components of the type I interferon (IFN) receptor, but
      their interrelationship and role in ligand binding were not clear. To study these
      issues, we stably expressed and characterized the two polypeptides in host murine
      cells. In human cells, native IFN-alpha/beta R is a 102-kDa protein but upon
      reduction only a 51-kDa protein is detected. In host murine cells human IFN
      alpha/beta R was expressed as a 51-kDa protein. Host cells expressing IFN
      alpha/beta R bound IFN-alpha 2 with a high affinity (Kd of 3.6 nM), whereas cells
      expressing IFNAR exhibited no ligand binding. Upon coexpression of IFNAR and the
      51-kDa IFN-alpha/beta R, the affinity for IFN-alpha 2 was increased 10-fold,
      approaching that of the native receptor. We show by cross-linking that both the
      cloned (51-kDa) and native (102-kDa) IFN-alpha/beta R bind IFN-alpha 2 to form an
      intermediate product, while IFNAR associates with this product to form a ternary
      complex. Hence, IFNAR and IFN-alpha/beta R are components of a common type I IFN
      receptor, cooperating in ligand binding. Ligand-induced association of IFNAR and
      IFN-alpha/beta R probably triggers transmembrane signaling.

PMID- 7623816
TI  - Cellular targets for activation by the E2F1 transcription factor include DNA
      synthesis- and G1/S-regulatory genes.
AB  - Although a number of transfection experiments have suggested potential targets
      for the action of the E2F1 transcription factor, as is the case for many
      transcriptional regulatory proteins, the actual targets in their normal
      chromosomal environment have not been demonstrated. We have made use of a
      recombinant adenovirus containing the E2F1 cDNA to infect quiescent cells and
      then measure the activation of endogenous cellular genes as a consequence of E2F1
      production. We find that many of the genes encoding S-phase-acting proteins
      previously suspected to be E2F targets, including DNA polymerase alpha,
      thymidylate synthase, proliferating cell nuclear antigen, and ribonucleotide
      reductase, are indeed induced by E2F1. Several other candidates, including the
      dihydrofolate reductase and thymidine kinase genes, were only minimally induced
      by E2F1. In addition to the S-phase genes, we also find that several genes
      believed to play regulatory roles in cell cycle progression, such as the cdc2,
      cyclin A, and B-myb genes, are also induced by E2F1. Moreover, the cyclin E gene
      is strongly induced by E2F1, thus defining an autoregulatory circuit since cyclin
      E-dependent kinase activity can stimulate E2F1 transcription, likely through the
      phosphorylation and inactivation of Rb and Rb family members. Finally, we also
      demonstrate that a G1 arrest brought about by gamma irradiation is overcome by
      the overexpression of E2F1 and that this coincides with the enhanced activation
      of key target genes, including the cyclin A and cyclin E genes.

PMID- 7623817
TI  - Cooperative interaction of GATA-2 and AP1 regulates transcription of the
      endothelin-1 gene.
AB  - Endothelin-1 (ET-1) is a 21-amino-acid vasoactive peptide initially characterized
      as a product of endothelial cells. Reporter gene transfection experiments have
      indicated that a GATA site and an AP1 site are essential for ET-1 promoter
      function in endothelial cells, and GATA-2 appears to be the active GATA factor
      which regulates ET-1 expression. To look for interactions between AP1 and GATA-2,
      transactivation experiments were performed with expression vectors encoding c
      Jun, c-Fos, and GATA-2. Cooperativity between the AP1 complex and GATA-2 was
      observed as a synergistic increase in transcriptional activity of the ET-1
      reporter plasmid. In addition, AP1 was able to potentiate the action of GATA-2 on
      reporter constructs lacking a functional AP1 site. In a similar fashion, GATA-2
      was able to potentiate the action of AP1 despite deletion of the GATA site.
      Experiments with GATA-1 and GATA-3 expression vectors provided evidence that this
      capacity to interact with AP1 may be a characteristic of all GATA family members.
      Biochemical evidence for AP1-GATA interaction was provided by immunoprecipitation
      experiments. A GATA-2-specific antiserum was shown to immunoprecipitate in vitro
      synthesized Jun and Fos protein from reticulocyte lysate. Also, antisera directed
      against Jun and Fos were able to immunoprecipitate from nuclear extracts a GATA
      binding protein, indicating the association of AP1 and GATA proteins in vivo.

PMID- 7623818
TI  - SNF11, a new component of the yeast SNF-SWI complex that interacts with a
      conserved region of SNF2.
AB  - The yeast SNF-SWI complex is required for transcriptional activation of diverse
      genes and has been shown to alter chromatin structure. The complex has at least
      10 components, including SNF2/SWI2, SNF5, SNF6, SWI1/ADR6, and SWI3, and has been
      widely conserved in eukaryotes. Here we report the characterization of a new
      component. We identified proteins that interact in the two-hybrid system with the
      N-terminal region of SNF2, preceding the ATPase domain. In addition to SWI3, we
      recovered a new 19-kDa protein, designated SNF11. Like other SNF/SWI proteins,
      SNF11 functions as a transcriptional activator in genetic assays. SNF11 interacts
      with SNF2 in vitro and copurifies with the SNF-SWI complex from yeast cells.
      Using a specific antibody, we showed that SNF11 coimmunoprecipitates with members
      of the SNF-SWI complex and that SNF11 is tightly and stoichiometrically
      associated with the complex. Furthermore, SNF11 was detected in purified SNF-SWI
      complex by staining with Coomassie blue dye; its presence previously went
      unrecognized because it does not stain with silver. SNF11 interacts with a 40
      residue sequence of SNF2 that is highly conserved, suggesting that SNF11 homologs
      exist in other organisms.

PMID- 7623819
TI  - Astrocytes derived from p53-deficient mice provide a multistep in vitro model for
      development of malignant gliomas.
AB  - Loss or mutation of p53 is thought to be an early event in the malignant
      transformation of many human astrocytic tumors. To better understand the role of
      p53 in their growth and transformation, we developed a model employing cultured
      neonatal astrocytes derived from mice deficient in one (p53 +/-) or both (p53 -/
      ) p53 alleles, comparing them with wild-type (p53 +/+) cells. Studies of in vitro
      and in vivo growth and transformation were performed, and flow cytometry and
      karyotyping were used to correlate changes in growth with genomic instability.
      Early-passage (EP) p53 -/- astrocytes achieved higher saturation densities and
      had more rapid growth than EP p53 +/- and +/+ cells. The EP p53 -/- cells were
      not transformed, as they were unable to grow in serum-free medium or in nude
      mice. With continued passaging, p53 -/- cells exhibited a multistep progression
      to a transformed phenotype. Late-passage p53 -/- cells achieved saturation
      densities 50 times higher than those of p53 +/+ cells and formed large, well
      vascularized tumors in nude mice. p53 +/- astrocytes exhibited early loss of the
      remaining wild-type p53 allele and then evolved in a manner phenotypically
      similar to p53 -/- astrocytes. In marked contrast, astrocytes retaining both wild
      type p53 alleles never exhibited a transformed phenotype and usually senesced
      after 7 to 10 passages. Dramatic alterations in ploidy and karyotype occurred and
      were restricted to cells deficient in wild-type p53 following repeated passaging.
      The results of these studies suggest that loss of wild-type p53 function promotes
      genomic instability, accelerated growth, and malignant transformation in
      astrocytes.

PMID- 7623820
TI  - RelA is a potent transcriptional activator of the CD28 response element within
      the interleukin 2 promoter.
AB  - T-cell activation requires two different signals. The T-cell receptor's
      recognition of a specific antigen on antigen-presenting cells provides one, and
      the second signal comes from costimulatory molecules such as CD28. In contrast, T
      cells that are stimulated with antigen in the absence of the CD28 costimulatory
      signal can become anergic (nonresponsive). The CD28 response element (CD28RE) has
      been identified as the DNA element mediating interleukin 2 (IL-2) gene activation
      by CD28 costimulation. Our previous work demonstrates that the Rel/NF-kappa B
      family proteins c-Rel, RelA (p65), and NFKB1 (p50) are involved in the complex
      that binds to the CD28RE. We also showed that c-Rel, but not NFKB1 (p50), can
      bind to the CD28RE and activate CD28RE-driven transcription in cotransfection
      assays. However, the role of RelA (p65) in CD28 signaling has not yet been
      addressed. We provide evidence that RelA (p65) itself bound directly to the
      CD28RE of the IL-2 promoter and other lymphokine promoters. In addition, RelA
      (p65) was a potent transcriptional activator of the CD28RE in vivo. We show that
      a RelA (p65)-c-Rel heterodimer bound to the CD28RE and synergistically activated
      the CD28RE enhancer activity. We also demonstrate that activated Raf-1 kinase
      synergized with RelA (p65) in activating the CD28RE enhancer activity.
      Interestingly, a soluble anti-CD28 monoclonal antibody alone, in the absence of
      other stimuli, also synergized with RelA (p65) in activating the CD28RE.
      Furthermore, we show that RelA (p65) activated expression of the wild-type IL-2
      promoter but not the CD28RE-mutated IL-2 promoter. A combination of RelA (p65)
      and NFKB1 (p50) also activated the IL-2 promoter through the CD28RE site. These
      results demonstrate the functional regulation of the CD28RE, within the IL-2
      promoter, by Rel/NF-kappa B transcription factors.

PMID- 7623821
TI  - Regulation of Gax homeobox gene transcription by a combination of positive
      factors including myocyte-specific enhancer factor 2.
AB  - Homeobox-containing genes play an essential role in basic processes during
      embryogenesis and development, but little is known about the regulation of their
      expression. To elucidate regulatory networks that govern homeobox gene
      expression, we defined the core promoter of the mouse Gax homeobox gene and
      characterized its interactions with cellular proteins. Transient transfection
      experiments revealed Gax promoter activity in several cell types. Deletion
      analysis defined a 138-bp minimal promoter fragment between positions -125 and
      +13 relative to the transcription initiation site. Mutagenesis and protein-DNA
      binding assays suggested that at least three positive factors interact with this
      fragment and are required for transcriptional activity. One of these factors, HRF
      1, recognizes a cis element consisting of an inverted palindromic motif. A second
      factor is Sp1, that binds to a G/C-rich element. The third is the MADS box factor
      referred to as MEF2 or RSRF. Mutations in the MEF2/RSRF site had the greatest
      effect on transcription in cell types that expressed the highest levels of
      endogenous MEF2 activity. Conversely, overexpression of MEF2A transactivated the
      Gax promoter more efficiently in cells lacking endogenous MEF2. These data
      provide evidence for a direct transcriptional link between members of the MADS
      and homeobox families of transcription factors.

PMID- 7623822
TI  - Adenovirus type 2 preferentially stimulates polymerase III transcription of Alu
      elements by relieving repression: a potential role for chromatin.
AB  - The number of Alu transcripts that accumulate in HeLa and other human cells is
      normally very low; however, infection with adenovirus type 5 increases the
      expression of Alu elements dramatically, indicating that the potential for
      polymerase III (pol III)-dependent Alu transcription in vivo is far greater than
      generally observed (B. Panning and J.R. Smiley, Mol. Cell. Biol. 13:3231-3244,
      1993). In this study, we employed nuclear run-on in combination with a novel
      RNase H-based assay to investigate transcription from uninfected and adenovirus
      type 2-infected nuclei, as well as genomic DNAs from uninfected and infected
      cells. When performed in the presence of excess uninfected nuclear extract, such
      assays revealed that (i) the vast majority of transcriptionally competent Alu
      elements in nuclei are masked from the pol III transcriptional machinery and (ii)
      the induction of Alu expression upon adenovirus infection can be largely
      accounted for by an increased availability of these elements to the pol III
      transcription machinery. We also investigated the role of H1 histone for
      silencing of Alu genes and, in comparison, mouse B2 repetitive elements.
      Depletion of H1 led to an approximately 17-fold activation of B2 repetitive
      elements but did not change Alu transcription relative to that of constitutively
      expressed 5S rRNA genes. These results are consistent with the view that Alu
      repeats are efficiently sequestered by chromatin proteins, that such masking
      cannot be accounted for by nonspecific H1-dependent repression, and that
      adenovirus infection at least partially overrides the repressive mechanism(s).

PMID- 7623823
TI  - Mutations in RAD27 define a potential link between G1 cyclins and DNA
      replication.
AB  - The yeast Saccharomyces cerevisiae has three G1 cyclin (CLN) genes with
      overlapping functions. To analyze the functions of the various CLN genes, we
      examined mutations that result in lethality in conjunction with loss of cln1 and
      cln2. We have isolated alleles of RAD27/ERC11/YKL510, the yeast homolog of the
      gene encoding flap endonuclease 1, FEN-1.cln1 cln2 rad27/erc11 cells arrest in S
      phase; this cell cycle arrest is suppressed by the expression of CLN1 or CLN2 but
      not by that of CLN3 or the hyperactive CLN3-2. rad27/erc11 mutants are also
      defective in DNA damage repair, as determined by their increased sensitivity to a
      DNA-damaging agent, increased mitotic recombination rates, and increased
      spontaneous mutation rates. Unlike the block in cell cycle progression, these
      phenotypes are not suppressed by CLN1 or CLN2. CLN1 and CLN2 may activate an
      RAD27/ERC11-independent pathway specific for DNA synthesis that CLN3 is incapable
      of activating. Alternatively, CLN1 and CLN2 may be capable of overriding a
      checkpoint response which otherwise causes cln1 cln2 rad27/erc11 cells to arrest.
      These results imply that CLN1 and CLN2 have a role in the regulation of DNA
      replication. Consistent with this, GAL-CLN1 expression in checkpoint-deficient,
      mec1-1 mutant cells results in both cell death and increased chromosome loss
      among survivors, suggesting that CLN1 overexpression either activates defective
      DNA replication or leads to insensitivity to DNA damage.

PMID- 7623824
TI  - DNA ligase I mediates essential functions in mammalian cells.
AB  - DNA replication, repair, and recombination are essential processes in mammalian
      cells. Hence, the application of gene targeting to the study of these DNA
      metabolic pathways requires the creation of nonnull mutations. We have developed
      a method for introducing partially defective mutants in murine embryonic stem
      cells that circumvents the problem of cellular lethality of targeted mutations at
      essential loci. Using this approach, we have determined that mammalian DNA ligase
      I is essential for cell viability. Thus, DNA ligases II and III are not redundant
      with DNA ligase I for the function(s) associated with cell proliferation. Partial
      complementation of the lethal DNA ligase I null mutation allowed the creation of
      deficient embryonic stem cell lines. We found that a wild-type DNA ligase I cDNA,
      as well as a variant DNA ligase I cDNA, was able to rescue the lethality of the
      homozygous null mutation, whereas an N-terminal deletion mutant consisting of the
      minimal DNA ligase I catalytic domain was not. This observation demonstrates that
      sequences outside the DNA ligase I catalytic domain are essential for DNA ligase
      I function in vivo.

PMID- 7623825
TI  - The carboxyl-terminal transactivation domain of heat shock factor 1 is negatively
      regulated and stress responsive.
AB  - We have characterized a stress-responsive transcriptional activation domain of
      mouse heat shock factor 1 (HSF1) by using chimeric GAL4-HSF1 fusion proteins.
      Fusion of the GAL4 DNA-binding domain to residues 124 to 503 of HSF1 results in a
      chimeric factor that binds DNA yet lacks any transcriptional activity.
      Transactivation is acquired upon exposure to heat shock or by deletion of a
      negative regulatory domain including part of the DNA-binding-domain-proximal
      leucine zippers. Analysis of a collection of GAL4-HSF1 deletion mutants revealed
      the minimal region for the constitutive transcriptional activator to map within
      the extreme carboxyl-terminal 108 amino acids, corresponding to a region rich in
      acidic and hydrophobic residues. Loss of residues 395 to 425 or 451 to 503, which
      are located at either end of this activation domain, severely diminished
      activity, indicating that the entire domain is required for transactivation. The
      minimal activation domain of HSF1 also confers enhanced transcriptional response
      to heat shock or cadmium treatment. These results demonstrate that the
      transcriptional activation domain of HSF1 is negatively regulated and that the
      signal for stress induction is mediated by interactions between the amino
      terminal negative regulator and the carboxyl-terminal transcriptional activation
      domain.

PMID- 7623826
TI  - Multiple layers of regulation of human heat shock transcription factor 1.
AB  - Upon heat stress, monomeric human heat shock transcription factor 1 (hHSF1) is
      converted to a trimer, acquires DNA-binding ability, is transported to the
      nucleus, and becomes transcriptionally competent. It was not known previously
      whether these regulatory changes are caused by a single activation event or
      whether they occur independently from one another, providing a multilayered
      control that may prevent inadvertant activation of hHSF1. Comparison of wild-type
      and mutant hHSF1 expressed in Xenopus oocytes and human HeLa cells suggested that
      retention of hHSF1 in the monomeric form depends on hydrophobic repeats (LZ1 to
      LZ3) and a carboxy-terminal sequence element in hHSF1 as well as on the presence
      of a titratable factor in the cell. Oligomerization of hHSF1 appears to induce
      DNA-binding activity as well as to uncover an amino-terminally located nuclear
      localization signal. A mechanism distinct from that controlling oligomerization
      regulates the transcriptional competence of hHSF1. Components of this mechanism
      were mapped to a region, including LZ2 and nearby sequences downstream from LZ2,
      that is clearly separated from the carboxy-terminally located transcription
      activation domain(s). We propose the existence of a fold-back structure that
      masks the transcription activation domain in the unstressed cell but is opened up
      by modification of hHSF1 and/or binding of a factor facilitating hHSF1 unfolding
      in the stressed cell. Activation of hHSF1 appears to involve at least two
      independently regulated structural transitions.

PMID- 7623827
TI  - Adrenocortical function and regulation of the steroid 21-hydroxylase gene in NGFI
      B-deficient mice.
AB  - The immediate-early gene NGFI-B encodes an orphan nuclear receptor that binds DNA
      as a monomer and activates transcription through a canonical response element
      (NBRE). NGFI-B is expressed under basal conditions and in response to external
      stimuli in many mammalian tissues. In particular, NGFI-B expression is
      dramatically elevated in the adrenal cortex in response to stress and in Y1
      adrenocortical cells in response to adrenocorticotropin. NGFI-B activates
      transcription through an NBRE of the gene encoding 21-hydroxylase (P450c21) in Y1
      cells. Steroidogenic factor 1 (SF-1), a homolog of NGFI-B, also activates the
      P450c21 promoter. To examine the influence of these factors on P450c21 expression
      in vivo and the function of the hypothalamic-pituitary-adrenocortical axis as a
      whole, we generated NGFI-B (-/-) mice. These mice thrive and reproduce normally
      and maintain normal basal adrenocorticotropin, corticosterone, and P450c21 mRNA
      levels. In response to increases in adrenocorticotropin, NGFI-B (-/-) and wild
      type mice demonstrated equivalent increases in serum corticosterone levels.
      Furthermore, and in contrast to in vitro results, no increases in P450c21 mRNA
      levels were observed in response to increases in adrenocorticotropin in NGFI-B (
      /-) or wild-type mice. While SF-1 mRNA levels were not increased with increased
      steroidogenic demand, adrenal expression of Nurr1, a close homolog of NGFI-B, was
      induced to a greater extent by lipopolysaccharide in NGFI-B (-/-) mice than in
      wild-type mice. Finally, when the administration of dexamethasone for suppression
      was stopped, P450c21 mRNA and serum corticosterone levels recovered at the same
      rate in wild-type and NGFI-B (-/-) mice. Thus, while NGFI-B appears poised to
      affect the structure and function of the adrenal gland, the gland functions
      normally in its absence, suggesting that other factors, including Nurr1 and SF-1,
      are sufficient to drive P450c21 expression in mice and maintain normal
      steroidogenesis.

PMID- 7623828
TI  - A functional T-cell receptor signaling pathway is required for p95vav activity.
AB  - Stimulation of the T-cell antigen receptor (TCR) induces activation of multiple
      tyrosine kinases, resulting in phosphorylation of numerous intracellular
      substrates. One substrate is p95vav, which is expressed exclusively in
      hematopoietic and trophoblast cells. It contains a number of structural motifs,
      including Src homology 2, Src homology 3, and pleckstrin homology domains and a
      putative guanine nucleotide exchange domain. The role of p95vav in TCR-mediated
      signaling processes is unclear. Here, we show that overexpression of p95vav alone
      in Jurkat T cells leads to activation of the nuclear factors, including NFAT,
      involved in interleukin-2 expression. Furthermore, p95vav synergizes with TCR
      stimulation in inducing NFAT- and interleukin-2-dependent transcription. In
      contrast, NFAT activation by a G-protein-coupled receptor is not modulated by
      p95vav overexpression, suggesting that the effect is specific to the TCR
      signaling pathways. Although removal of the first 67 amino acids of p95vav
      activates its transforming potential in NIH 3T3 cells, this region appears to be
      required for its function in T cells. We further demonstrate that the p95vav
      induced NFAT activation is not mimicked by Ras activation, though its function is
      dependent upon Ras and Raf. Furthermore, the activating function of p95vav is
      blocked by FK506, suggesting that its activity also depends on calcineurin. To
      further dissect p95vav involvement in TCR signaling, we analyzed various Jurkat
      mutants deficient in TCR signaling function or TCR expression and showed that an
      intact TCR signaling pathway is required for p95vav to function. However,
      overexpression of p95vav does not appear to influence TCR-induced protein
      tyrosine phosphorylation or increases in cytoplasmic free calcium. Taken
      together, our data suggest that p95vav plays an important role at an yet
      unidentified proximal position in the TCR signaling cascade.

PMID- 7623829
TI  - Cyclin A-associated kinase activity is rate limiting for entrance into S phase
      and is negatively regulated in G1 by p27Kip1.
AB  - We have created fibroblast cell lines that express cyclin A under the control of
      a tetracycline-repressible promoter. When stimulated to reenter the cell cycle
      after serum withdrawal, these cells were advanced prematurely into S phase by
      induction of cyclin A. In an asynchronous population, induction of cyclin A
      caused a decrease in the percentage of cells in G1. These results demonstrate
      that expression of cyclin A is rate limiting for the G1-to-S transition and
      suggest that cyclin A can function as a G1 cyclin. Although the level of
      exogenous cyclin A was constant throughout the cell cycle, its associated kinase
      activity increased as cells approached S phase. Low kinase activity in early G1
      was found to correlate with the presence of p27Kip1 in cyclin A-associated
      complexes, while high kinase activity in late G1 was correlated with its absence.
      These results suggest that a function of p27Kip1 in G1 is to prevent premature
      activation of cyclin A-associated kinase. Cyclin A expression in early G1 led to
      phosphorylation of the product of the retinoblastoma susceptibility gene (pRb).
      Thus, cyclin A expression can be rate limiting for pRb phosphorylation,
      implicating pRb as a physiological substrate of the cyclin A-dependent kinase.
      Taken together, these results demonstrate that deregulated expression of cyclin A
      can perturb the normal regulation of the G1-to-S transition.

PMID- 7623831
TI  - Nucleolar association of fibroblast growth factor 3 via specific sequence motifs
      has inhibitory effects on cell growth.
AB  - The dual subcellular fate of fibroblast growth factor 3 (FGF3) is determined by
      the competing effects of amino-terminal signals for nuclear localization and
      secretion (P. Kiefer, P. Acland, D. Pappin, G. Peters, and C. Dickson, EMBO J.
      13:4126-4136, 1994). Mutation analysis has implicated additional basic domains in
      the carboxy-terminal region of the protein as necessary for nuclear uptake and
      the association of FGF3 with the nucleoli. Immunogold electron microscopy shows
      that FGF3 is predominantly within the dense fibrillar component of the nucleolus.
      A form of FGF3 that localizes exclusively in the nucleus and nucleolus was
      generated by removing signals for secretion, and expression of this nonsecreted
      FGF3 in a mammary epithelial cell line resulted in slowly growing colonies of
      enlarged cells. Thus, nuclear import and nucleolar association of FGF3 are
      determined by the concerted interaction of several distinct motifs, and the
      exclusive production of the nuclear isoform can inhibit DNA synthesis and cell
      proliferation.

PMID- 7623830
TI  - RSK3 encodes a novel pp90rsk isoform with a unique N-terminal sequence: growth
      factor-stimulated kinase function and nuclear translocation.
AB  - A novel pp90rsk Ser/Thr kinase (referred to as RSK3) was cloned from a human cDNA
      library. The RSK3 cDNA encodes a predicted 733-amino-acid protein with a unique N
      terminal region containing a putative nuclear localization signal. RSK3 mRNA was
      widely expressed (but was predominant in lung and skeletal muscle). By using
      fluorescence in situ hybridization, the human RSK3 gene was localized to band q27
      of chromosome 6. Hemagglutinin epitope-tagged RSK3 was expressed in transiently
      transfected COS cells. Growth factors, serum, and phorbol ester stimulated
      autophosphorylation of recombinant RSK3 and its kinase activity toward several
      protein substrates known to be phosphorylated by RSKs. However, the relative
      substrate specificity of RSK3 differed from that reported for other isoforms.
      RSK3 also phosphorylated potential nuclear target proteins including c-Fos and
      histones. Furthermore, although RSK3 was inactivated by protein phosphatase 2A in
      vitro, the enzyme was not activated by ERK2/mitogen-activated protein (MAP)
      kinase. In contrast, the kinase activity of another epitope-tagged RSK isoform
      (RSK-1) was significantly increased by in vitro incubation with ERK2/MAP kinase.
      Finally, we used affinity-purified RSK3 antibodies to demonstrate by
      immunofluorescence that endogenous RSK3 undergoes serum-stimulated nuclear
      translocation in cultured HeLa cells. These results provide evidence that RSK3 is
      a third distinct isoform of pp90rsk which translocates to the cell nucleus,
      phosphorylates potential nuclear targets, and may have a unique upstream
      activator. RSK3 may therefore subserve a discrete physiologic role(s) that
      differs from those of the other two known mammalian RSK isoforms.

PMID- 7623832
TI  - Accessibility of a glucocorticoid response element in a nucleosome depends on its
      rotational positioning.
AB  - Gene expression requires binding of transcription factors to their cognate DNA
      response elements, the latter being often integrated into sequence-specifically
      positioned nucleosomes. To investigate the constraints imposed on factor-DNA
      recognition by the nucleosomal organization, we studied the binding of
      glucocorticoid receptor to a single glucocorticoid response element (GRE)
      displaying four different rotational frames in three different translational
      positions in reconstituted nucleosomes. We demonstrate that rotational setting of
      the GRE per se is important for its accessibility. Furthermore, the effects of
      rotational positioning of the GRE are different for different translational
      positions of the GRE in the nucleosome. A GRE placed near the nucleosomal dyad is
      totally blocked by rotating it 180 degrees so that the major groove of the GRE
      faces the histone octamer. If, on the other hand, the GRE is placed about 40 bp
      from the nucleosome dyad, then the 180 degrees rotation of the GRE still allows
      glucocorticoid receptor binding, albeit with a sixfold lower affinity than the
      peripherally oriented GRE. This suggests that both the rotational positioning and
      the translational positioning function as a framework for transcription factor
      response elements in gene regulation.

PMID- 7623833
TI  - Cooperation between elements of an organ-specific transcriptional enhancer in
      animals.
AB  - The elastase I gene enhancer that specifies high levels of pancreatic
      transcription comprises three functional elements (A, B, and C). When assayed
      individually in transgenic mice, homomultimers of A are acinar cell specific,
      those of B are islet specific, and those of C are inactive. To determine how the
      elements interact in the elastase I enhancer and to investigate further the role
      of the C element, we have examined the activity of the three possible
      combinations of synthetic double elements in transgenic animals. Combining the A
      and B elements reconstitutes the exocrine plus endocrine specificity of the
      intact enhancer with an increased activity in acinar cells compared with that in
      the A homomultimer. The B element therefore plays a dual role: in islet cells it
      is capable of activating transcription, whereas in acinar cells it is inactive
      alone but greatly augments the activity specified by the A element. The C element
      augments the activity of either the A or B element without affecting their
      pancreatic cell type specificity. The roles of each element were verified by
      examining the effects of mutational inactivation of each element within the
      context of the elastase I enhancer. These results demonstrated that when tested
      in animals, the individual enhancer elements can perform discrete, separable
      functions that combine additively for cell type specificity and cooperatively for
      the overall strength of a multielement stage- and site-specific transcriptional
      enhancer.

PMID- 7623834
TI  - Both coding exons of the c-myc gene contribute to its posttranscriptional
      regulation in the quiescent liver and regenerating liver and after protein
      synthesis inhibition.
AB  - In vivo, the steady-state level of c-myc mRNA is mainly controlled by
      posttranscriptional mechanisms. Using a panel of transgenic mice in which various
      versions of the human c-myc proto-oncogene were under the control of major
      histocompatibility complex H-2Kb class I regulatory sequences, we have shown that
      the 5' and the 3' noncoding sequences are dispensable for obtaining a regulated
      expression of the transgene in adult quiescent tissues, at the start of liver
      regeneration, and after inhibition of protein synthesis. These results indicated
      that the coding sequences were sufficient to ensure a regulated c-myc expression.
      In the present study, we have pursued this analysis with transgenes containing
      one or the other of the two c-myc coding exons either alone or in association
      with the c-myc 3' untranslated region. We demonstrate that each of the exons
      contains determinants which control c-myc mRNA expression. Moreover, we show that
      in the liver, c-myc exon 2 sequences are able to down-regulate an otherwise
      stable H-2K mRNA when embedded within it and to induce its transient accumulation
      after cycloheximide treatment and soon after liver ablation. Finally, the use of
      transgenes with different coding capacities has allowed us to postulate that the
      primary mRNA sequence itself and not c-Myc peptides is an important component of
      c-myc posttranscriptional regulation.

PMID- 7623835
TI  - A mutational analysis of the yeast proliferating cell nuclear antigen indicates
      distinct roles in DNA replication and DNA repair.
AB  - The saccharomyces cerevisiae proliferating cell nuclear antigen (PCNA), encoded
      by the POL30 gene, is essential for DNA replication and DNA repair processes.
      Twenty-one site-directed mutations were constructed in the POL30 gene, each
      mutation changing two adjacently located charged amino acids to alanines.
      Although none of the mutant strains containing these double-alanine mutations as
      the sole source of PCNA were temperature sensitive or cold sensitive for growth,
      about a third of the mutants showed sensitivity to UV light. Some of those UV
      sensitive mutants had elevated spontaneous mutation rates. In addition, several
      mutants suppressed a cold-sensitive mutation in the CDC44 gene, which encodes the
      large subunit of replication factor C. A cold-sensitive mutant, which was
      isolated by random mutagenesis, showed a terminal phenotype at the restrictive
      temperature consistent with a defect in DNA replication. Several mutant PCNAs
      were expressed and purified from Escherichia coli, and their in vitro properties
      were determined. The cold-sensitive mutant (pol30-52, S115P) was a monomer,
      rather than a trimer, in solution. This mutant was deficient for DNA synthesis in
      vitro. Partial restoration of DNA polymerase delta holoenzyme activity was
      achieved at 37 degrees C but not at 14 degrees C by inclusion of the
      macromolecular crowding agent polyethylene glycol in the assay. The only other
      mutant (pol30-6, DD41,42AA) that showed a growth defect was partially defective
      for interaction with replication factor C and DNA polymerase delta but completely
      defective for interaction with DNA polymerase epsilon. Two other mutants
      sensitive to DNA damage showed no defect in vitro. These results indicate that
      the latter mutants are specifically impaired in one or more DNA repair processes
      whereas pol30-6 and pol30-52 mutants show their primary defects in the basic DNA
      replication machinery with probable associated defects in DNA repair. Therefore,
      DNA repair requires interactions between repair-specific protein(s) and PCNA,
      which are distinct from those required for DNA replication.

PMID- 7623836
TI  - scute (sis-b) function in Drosophila sex determination.
AB  - The primary sex determination signal, the X chromosome-to-autosome (X/A) ratio,
      controls the choice of sexual identity in the Drosophila melanogaster embryo by
      regulating the activity of the early promoter of the Sex-lethal gene, Sxl-Pe.
      This promoter is activated in females (2X/2A), while it remains off in males
      (1X/2A). Promoter activation in females is dependent upon X-linked numerator
      genes. One of these genes, sisterless-b (sis-b), corresponds to the scute (sc)
      locus of the achaete-scute complex, and it encodes a helix-loop-helix
      transcription factor. In the studies reported here we have used monoclonal
      antibodies to study the expression and functioning of the sc(sis-b) protein. Sc
      is first detected at nuclear cycle 6 to 7, well before Sxl-Pe is first active. At
      this stage, the protein is in the cytoplasm, not the nucleus. Only after the
      formation of the syncytial blastoderm, at nuclear cycle 10 to 11, does a
      substantial fraction of the protein enter the nucleus, and this nuclear import
      closely coincides with the initial activation of Sxl-Pe. Consistent with the idea
      that the dose of sc(sis-b) is critical for its function as an X-chromosome
      counting element, wild-type syncytial blastoderm embryos could be grouped into
      two classes based on the level of protein. Western blot (immunoblot) analysis
      demonstrates that this difference in protein level correlates directly with the
      activity state of the Sxl gene. Finally, we provide the first direct evidence
      that Sc forms heteromeric complexes in vivo in early embryos with the maternally
      derived helix-loop-helix protein Daughterless. This in vivo complex is likely to
      be critical for Sc function in Sxl-Pe activation.

PMID- 7623837
TI  - Multiple genes, including a member of the AAA family, are essential for
      degradation of unassembled subunit 2 of cytochrome c oxidase in yeast
      mitochondria.
AB  - Cytochrome c oxidase consists of three mitochondrion- and several nucleus-encoded
      subunits. We previously found that in a mutant of Saccharomyces cerevisiae
      lacking nucleus-encoded subunit 4 of this enzyme (CoxIV), subunits 2 and 3 (CoxII
      and CoxIII), both encoded by the mitochondrial DNA, were unstable and rapidly
      degraded in mitochondria, presumably because the subunits cannot assemble
      normally. To analyze the molecular machinery involved in this proteolytic
      pathway, we obtained four mutants defective in the degradation of unassembled
      CoxII (osd mutants) by screening CoxIV-deficient cells for the accumulation of
      CoxII. All of the mutants were recessive and were classified into three different
      complementation groups. Tetrad analyses revealed that the phenotype of each
      mutant was caused by a single nuclear mutation. These results suggest strongly
      that at least three nuclear genes (the OSD genes) are required for this
      degradation system. Interestingly, degradation of CoxIII was not affected in the
      mutants, implying that the two subunits are degraded by distinct pathways. We
      also cloned the OSD1 gene by complementation of the temperature sensitivity of
      osd1-1 mutants with a COXIV+ genetic background on a nonfermentable glycerol
      medium. We found it to encode a member of a family (the AAA family) of putative
      ATPases, which proved to be identical to recently described YME1 and YTA11.
      Immunological analyses revealed that Osd1 protein is localized to the
      mitochondrial inner membrane. Disruption of the predicted ATP-binding cassette by
      site-directed mutagenesis eliminated biological activities, thereby underscoring
      the importance of ATP for function.

PMID- 7623838
TI  - Studies of point mutants define three essential paired nucleotides in the domain
      5 substructure of a group II intron.
AB  - Domain 5 (D5) is a highly conserved, largely helical substructure of group II
      introns that is essential for self-splicing. Only three of the 14 base pairs
      present in most D5 structures (A2.U33, G3.U32, and C4.G31) are nearly invariant.
      We have studied effects of point mutations of those six nucleotides on self
      splicing and in vivo splicing of aI5 gamma, an intron of the COXI gene of
      Saccharomyces cerevisiae mitochondria. Though none of the point mutations blocked
      self-splicing under one commonly used in vitro reaction condition, the most
      debilitating mutations were at G3 and G4. Following mitochondrial Biolistic
      transformation, it was found that mutations at A2, G3, and C4 blocked respiratory
      growth and splicing while mutations at the other sites had little effect on
      either phenotype. Intra-D5 second-site suppressors showed that pairing between
      nucleotides at positions 2 and 33 and 4 and 31 is especially important for D5
      function. At the G3.U32 wobble pair, the mutant A.U pair blocks splicing, but a
      revertant of that mutant that can form an A+.C base pair regains some splicing. A
      dominant nuclear suppressor restores some splicing to the G3A mutant but not the
      G3U mutant, suggesting that a purine is required at position 3. These findings
      are discussed in terms of the hypothesis of Madhani and Guthrie (H. D. Madhani
      and C. Guthrie, Cell 71:803-817, 1992) that helix 1 formed between yeast U2 and
      U6 small nuclear RNAs may be the spliceosomal cognate of D5.

PMID- 7623839
TI  - Identification of a novel p53 promoter element involved in genotoxic stress
      inducible p53 gene expression.
AB  - p53 is recruited in response to DNA-damaging genotoxic stress and plays an
      important role in maintaining the integrity of the genome. We show that exposure
      of cells to various genotoxic agents, including anticancer drugs such as
      mitomycin and 5-fluorouracil, results in an increase in p53 mRNA levels and in
      p53 promoter activation, indicating that the p53 genotoxic stress response is
      partly regulated at the transcriptional level. The results of the p53 promoter
      analysis show that a novel p53 promoter element, termed a p53 core promoter
      element (from -70 to -46), is essential for basal p53 promoter activity and
      promoter activation induced by genotoxic agents such as anticancer drugs and UV.
      Although a kappa B motif partially overlaps with this element and those genotoxic
      agents activate NF-kappa B, it does not play a major role in p53 genotoxic stress
      response: NF-kappa B p65 expression did not induce significant p53 promoter
      activation, and NF-kappa B inhibitors (N-acetyl cysteine and I kappa B alpha) did
      not inhibit genotoxic stress-inducible p53 promoter activation. Finally, we
      characterized nuclear factors, the binding of which to the p53 core promoter
      element is essential for basal p53 promoter activity and p53 promoter activation
      induced by genotoxic agents.

PMID- 7623840
TI  - The histidyl-tRNA synthetase-related sequence in the eIF-2 alpha protein kinase
      GCN2 interacts with tRNA and is required for activation in response to starvation
      for different amino acids.
AB  - Protein kinase GCN2 is a multidomain protein that contains a region homologous to
      histidyl-tRNA synthetases juxtaposed to the kinase catalytic moiety. Previous
      studies have shown that in response to histidine starvation, GCN2 phosphorylates
      eukaryotic initiation factor 2 (eIF-2), to induce the translational expression of
      GCN4, a transcriptional activator of genes subject to the general amino acid
      control. It was proposed that the synthetase-related sequences of GCN2 stimulate
      the activity of the kinase by interacting directly with uncharged tRNA that
      accumulates during amino acid limitation. In addition to histidine starvation,
      expression of GCN4 is also regulated by a number of other amino acid limitations.
      Questions that we posed in this report are whether uncharged tRNA is the most
      direct regulator of GCN2 and whether the function of this kinase is required to
      recognize each of the different amino acid starvation signals. We show that GCN2
      phosphorylation of eIF-2, and the resulting general amino acid control pathway,
      is stimulated in response to starvation for each of several different amino
      acids, in addition to histidine limitation. Cells containing a defective
      aminoacyl-tRNA synthetase also stimulated GCN2 phosphorylation of eIF-2 in the
      absence of amino acid starvation, indicating that uncharged tRNA levels are the
      most direct regulator of GCN2 kinase. Using a Northwestern blot (RNA binding)
      assay, we show that uncharged tRNA can bind to the synthetase-related domain of
      GCN2. Mutations in the motif 2 sequence conserved among class II synthetases,
      including histidyl-tRNA synthetases, impair the ability of this synthetase
      related domain to bind tRNA and abolish GCN2 phosphorylation of eIF-2 required to
      stimulate the general amino acid control response. These in vivo and in vitro
      experiments indicate that synthetase-related sequences regulate GCN2 kinase
      function by monitoring the levels of multiple uncharged tRNAs that accumulate
      during amino acid limitations.

PMID- 7623842
TI  - B-cell-specific DNA binding by an E47 homodimer.
AB  - B cells express a unique E-box-binding activity that contains basic helix-loop
      helix (bHLH) proteins encoded by the E2A gene. E2A proteins play a central role
      in immunoglobulin gene transcription and are also required for the generation of
      the B-lymphocyte lineage. In muscle, E2A proteins bind DNA as heterodimers with
      muscle-specific bHLH partners, such as MyoD and myogenin, and these heterodimers
      are thought to be both necessary and sufficient for muscle determination in
      cultured cells. Our results indicate that in B cells, the bHLH partners for E2A
      proteins are not B-cell-restricted proteins, but are the E2A proteins themselves.
      UV cross-linking, gel purification, and the analysis of "forced heterodimers"
      indicate that BCF1 is primarily a homodimer of the E2A protein E47. Since E47 is
      widely expressed, our results argue for a difference in the inherent DNA-binding
      properties of the E47 protein in B cells and may help explain the restricted B
      lineage defect observed in E2A-deficient mice.

PMID- 7623841
TI  - A 10-amino-acid sequence in the N-terminal A/B domain of thyroid hormone receptor
      alpha is essential for transcriptional activation and interaction with the
      general transcription factor TFIIB.
AB  - The effects of the thyroid hormone (3,5,3'-triiodo-L-thyronine [T3]) on gene
      transcription are mediated by nuclear T3 receptors (T3Rs). alpha- and beta
      isoform T3Rs (T3R alpha and -beta) are expressed from different genes and are
      members of a superfamily of ligand-dependent transcription factors that also
      includes the receptors for steroid hormones, vitamin D, and retinoids. Although
      T3 activates transcription by mediating a conformational change in the C-terminal
      approximately 220-amino-acid ligand-binding domain (LBD), the fundamental
      mechanisms of T3R-mediated transcriptional activation remain to be determined. We
      found that deletion of the 50-amino-acid N-terminal A/B domain of chicken T3R
      alpha (cT3R alpha) decreases T3-dependent stimulation of genes regulated by
      native thyroid hormone response elements about 10- to 20-fold. The requirement of
      the A/B region for transcriptional activation was mapped to amino acids 21 to 30,
      which contain a cluster of five basic amino acids. The A/B region of cT3R alpha
      is not required for T3 binding or for DNA binding of the receptor as a
      heterodimer with retinoid X receptor. In vitro binding studies indicate that the
      N-terminal region of cT3R alpha interacts efficiently with TFIIB and that this
      interaction requires amino acids 21 to 30 of the A/B region. In contrast, the LBD
      interacts poorly with TFIIB. The region of TFIIB primarily involved in the
      binding of cT3R alpha includes an amphipathic alpha helix contained within
      residues 178 to 201. Analysis using a fusion protein containing the DNA-binding
      domain of GAL4 and the entire A/B region of cT3R alpha suggests that this region
      does not contain an intrinsic activation domain. These and other studies indicate
      that cT3R alpha mediates at least some of its effects through TFIIB in vivo and
      that the N-terminal region of DNA-bound cT3R alpha acts to recruit and/or
      stabilize the binding of TFIIB to the transcription complex. T3 stimulation could
      then result from ligand-mediated changes in the LBD which may lead to the
      interaction of other factors with cT3R alpha, TFIIB, and/or other components
      involved in the initiation of transcription.

PMID- 7623843
TI  - Mutational analysis of the Prt1 protein subunit of yeast translation initiation
      factor 3.
AB  - The Saccharomyces cerevisiae PRT1 gene product Prt1p is a component of
      translation initiation factor eIF-3, and mutations in PRT1 inhibit translation
      initiation. We have investigated structural and functional aspects of Prt1p and
      its gene. Transcript analysis and deletion of the PRT1 5' end revealed that
      translation of PRT1 mRNA is probably initiated at the second in-frame ATG in the
      open reading frame. The amino acid changes encoded by six independent temperature
      sensitive prt1 mutant alleles were found to be distributed throughout the central
      and C-terminal regions of Prt1p. The temperature sensitivity of each mutant
      allele was due to a single missense mutation, except for the prt1-2 allele, in
      which two missense mutations were required. In-frame deletion of an N-terminal
      region of Prt1p generated a novel, dominant-negative form of Prt1p that inhibits
      translation initiation even in the presence of wild-type Prt1p. Subcellular
      fractionation suggested that the dominant-negative Prt1p competes with wild-type
      Prt1p for association with a component of large Prt1p complexes and as a result
      inhibits the binding of wild-type Prt1p to the 40S ribosome.

PMID- 7623844
TI  - Activated H-ras rescues E1A-induced apoptosis and cooperates with E1A to overcome
      p53-dependent growth arrest.
AB  - The adenovirus E1A oncogene products stimulate DNA synthesis and cell
      proliferation but fail to transform primary baby rat kidney (BRK) cells because
      of the induction of p53-mediated programmed cell death (apoptosis).
      Overexpression of dominant mutant p53 (to abrogate wild-type p53 function) or
      introduction of apoptosis inhibitors, such as adenovirus E1B 19K or Bcl-2
      oncoproteins, prevents E1A-induced apoptosis and permits transformation of BRK
      cells. The ability of activated Harvey-ras (H-ras) to cooperate with E1A to
      transform BRK cells suggests that H-ras is capable of overcoming the E1A-induced,
      p53-dependent apoptosis. We demonstrate here that activated H-ras was capable of
      suppressing apoptosis induced by E1A and wild-type p53. However, unlike Bcl-2 and
      the E1B 19K proteins, which completely block apoptosis but not p53-dependent
      growth arrest, H-ras expression permitted DNA synthesis and cell proliferation in
      the presence of high levels of wild-type p53. The mechanism by which H-ras
      regulates apoptosis and cell cycle progression is thereby strikingly different
      from that of the E1B 19K and Bcl-2 proteins. BRK cells transformed with H-ras and
      the temperature sensitive murine mutant p53(val 135), which lack E1A, underwent
      growth arrest at the permissive temperature for wild-type p53. p53-dependent
      growth arrest, however, could be relieved by E1A expression. Thus, H-ras alone
      was insufficient and cooperation of H-ras and E1A was required to override growth
      suppression by p53. Our data further suggest that two complementary growth
      signals from E1A plus H-ras can rescue cell death and thus permit transformation.

PMID- 7623845
TI  - Structural analysis of TRAS1, a novel family of telomeric repeat-associated
      retrotransposons in the silkworm, Bombyx mori.
AB  - We characterized TRAS1, a retrotransposable element which was inserted into the
      telomeric repetitive sequence (CCTAA)n of the silkworm, Bombyx mori. The complete
      sequence of TRAS1, a stretch of 7.8 kb with a poly(A) tract at the 3' end, was
      determined. No long terminal repeat (LTR) was found at the termini of the
      element. TRAS1 contains gag- and pol-like open reading frames (ORFs) which are
      similar to those of non-LTR retrotransposons. The two ORFs overlap but are one
      nucleotide out of frame (+1 frameshift). Most of the approximately 250 copies of
      TRAS1 elements in the genome were highly conserved in the structure. Chromosomal
      in situ hybridization showed that TRAS1 elements are clustered at the telomeres
      of Bombyx chromosomes. A phylogenetic analysis using the amino acid sequence of
      the reverse transcriptase domain within the pol-like ORF revealed that TRAS1
      falls into one lineage with R1, which is a family of non-LTR retrotransposons
      inserted into the same site within the 28S ribosomal DNA unit in most insects.
      TRAS1 may have been derived from R1 and changed the target specificity so that
      TRAS1 inserts into the telomeric repetitive sequence (CCTAA)n. Southern
      hybridization and Bal 31 exonuclease analyses showed that TRAS1 elements are
      clustered proximal to the terminal long tract of (CCTAA)n. TRAS1 is a novel
      family of non-LTR retrotransposons which are inserted into the telomeric
      repetitive sequences as target sites.

PMID- 7623846
TI  - The cytoplasmic tyrosine kinase FER is associated with the catenin-like substrate
      pp120 and is activated by growth factors.
AB  - The FER gene encodes a cytoplasmic tyrosine kinase with a single SH2 domain and
      an extensive amino terminus. In order to understand the cellular function of the
      FER kinase, we analyzed the effect of growth factor stimulation on the
      phosphorylation and activity of FER. Stimulation of A431 cells and 3T3
      fibroblasts with epidermal growth factor or platelet-derived growth factor
      results in the phosphorylation of FER and two associated polypeptides. The
      associated polypeptides were shown to be the epidermal growth factor receptor or
      the platelet-derived growth factor receptor and a previously identified target,
      pp120. Since pp120 had previously been shown to interact with components of the
      cadherin-catenin complex, these results implicate FER in the regulation of cell
      cell interactions. The physical association of FER with pp120 was found to be
      constitutive and was mediated by a 400-amino-acid sequence in the amino terminus
      of FER. Analyses of that sequence revealed that it has the ability to form coiled
      coils and that it oligomerizes in vitro. The identification of a coiled coil
      sequence in the FER kinase and the demonstration that the sequence mediates
      association with a potential substrate suggest a novel mechanism for signal
      transduction by cytoplasmic tyrosine kinases.

PMID- 7623847
TI  - Association of SARFH (sarcoma-associated RNA-binding fly homolog) with regions of
      chromatin transcribed by RNA polymerase II.
AB  - Many oncogenes associated with human sarcomas are composed of a fusion between
      transcription factors and the N-terminal portions of two similar RNA-binding
      proteins, TLS and EWS. Though the oncogenic fusion proteins lack the RNA-binding
      domain and do not bind RNA, the contribution from the N-terminal portion of the
      RNA-binding protein is essential for their transforming activity. TLS and EWS
      associate in vivo with RNA polymerase II (Pol II) transcripts. To learn more
      about the target gene specificity of this interaction, the localization of a
      Drosophila melanogaster protein that has extensive sequence identity to the C
      terminal RNA-binding portions of TLS and EWS was studied in preparations of
      Drosophila polytene nuclei. cDNA clones encoding the full-length Drosophila TLS
      EWS homolog, SARFH (stands for sarcoma-associated RNA-binding fly homolog), were
      isolated. Functional similarity to TLS and EWS was revealed by the association of
      SARFH with Pol II transcripts in mammalian cells and by the ability of SARFH to
      elicit homologous down-regulation of the levels of the mammalian proteins. The
      SARFH gene is expressed in the developing Drosophila embryo from the earliest
      stages of cellularization and is subsequently found in many cell types. In
      preparations of polytene chromosomes from salivary gland nuclei, SARFH antibodies
      recognize their target associated with the majority of active transcription
      units, revealed by colocalization with the phosphorylated form of RNA Pol II. We
      conclude that SARFH and, by homology, EWS and TLS participate in a function
      common to the expression of most genes transcribed by RNA Pol II.

PMID- 7623848
TI  - An alternative eukaryotic DNA excision repair pathway.
AB  - DNA lesions induced by UV light, cyclobutane pyrimidine dimers, and (6
      4)pyrimidine pyrimidones are known to be repaired by the process of nucleotide
      excision repair (NER). However, in the fission yeast Schizosaccharomyces pombe,
      studies have demonstrated that at least two mechanisms for excising UV photo
      products exist; NER and a second, previously unidentified process. Recently we
      reported that S. pombe contains a DNA endonuclease, SPDE, which recognizes and
      cleaves at a position immediately adjacent to cyclobutane pyrimidine dimers and
      (6-4)pyrimidine pyrimidones. Here we report that the UV-sensitive S. pombe rad12
      502 mutant lacks SPDE activity. In addition, extracts prepared from the rad12-502
      mutant are deficient in DNA excision repair, as demonstrated in an in vitro
      excision repair assay. DNA repair activity was restored to wild-type levels in
      extracts prepared from rad12-502 cells by the addition of partially purified SPDE
      to in vitro repair reaction mixtures. When the rad12-502 mutant was crossed with
      the NER rad13-A mutant, the resulting double mutant was much more sensitive to UV
      radiation than either single mutant, demonstrating that the rad12 gene product
      functions in a DNA repair pathway distinct from NER. These data directly link
      SPDE to this alternative excision repair process. We propose that the SPDE
      dependent DNA repair pathway is the second DNA excision repair process present in
      S. pombe.

PMID- 7623849
TI  - Identification and characterization of Ral-binding protein 1, a potential
      downstream target of Ral GTPases.
AB  - Ral proteins constitute a distinct family of Ras-related GTPases. Although
      similar to Ras in amino acid sequence, Ral proteins are activated by a unique
      nucleotide exchange factor and inactivated by a distinct GTPase-activating
      protein. Unlike Ras, they fail to promote transformed foci when activated
      versions are expressed in cells. To identify downstream targets that might
      mediate a Ral-specific function, we used a Saccharomyces cerevisiae-based
      interaction assay to clone a novel cDNA that encodes a Ral-binding protein
      (RalBP1). RalBP1 binds specifically to the active GTP-bound form of RalA and not
      to a mutant Ral with a point mutation in its putative effector domain. In
      addition to a Ral-binding domain, RalBP1 also contains a Rho-GTPase-activating
      protein domain that interacts preferentially with Rho family member CDC42. Since
      CDC42 has been implicated in bud site selection in S. cerevisiae and filopodium
      formation in mammalian cells, Ral may function to modulate the actin cytoskeleton
      through its interactions with RalBP1.

PMID- 7623850
TI  - A skeletal muscle-specific enhancer regulated by factors binding to E and CArG
      boxes is present in the promoter of the mouse myosin light-chain 1A gene.
AB  - The mouse myosin light-chain 1A (MLC1A) gene, expressed in the atria of the adult
      heart, is one of the first muscle genes to be activated when skeletal as well as
      cardiac muscles form in the embryo. It is also transcribed in skeletal muscle
      cell lines at the onset of differentiation. Transient transfection assays of
      mouse skeletal muscle cell lines with DNA constructs containing MLC1A promoter
      fragments fused to the chloramphenicol acetyltransferase (CAT) gene show that the
      first 630 bp of the promoter is sufficient to direct expression of the reporter
      gene during myotube formation. Two E boxes located at bp -76 and -519 are
      necessary for this regulation. MyoD and myogenin proteins bind to them as
      heterodimers with E12 protein and, moreover, transactivate them in cotransfection
      experiments with the MLC1A promoter in nonmuscle cells. Interestingly, the effect
      of mutating each E box is less striking in primary cultures than in the C2 or
      Sol8 muscle cell line. A DNA fragment from bp -36 to -597 confers tissue- and
      stage-specific activity to the herpes simplex virus thymidine kinase promoter in
      both orientations, showing that the skeletal muscle-specific regulation of the
      MLC1A gene is under the control of a muscle-specific enhancer which extends into
      the proximal promoter region. At bp -89 is a diverged CArG box, CC(A/T)6AG, which
      binds the serum response factor (SRF) in myotube nuclear extracts, as does the
      wild-type sequence, CC(A/T)6GG. Both types of CArG box also bind a novel myotube
      enriched complex which has contact points with the AT-rich part of the CArG box
      and adjacent 3' nucleotides. Mutations within the CArG box distinguish between
      the binding of this complex and binding of SRF; only SRF binding is directly
      involved in the specific regulation of the MLC1A gene in skeletal muscle cell
      lines.

PMID- 7623851
TI  - Identification of positive and negative splicing regulatory elements within the
      terminal tat-rev exon of human immunodeficiency virus type 1.
AB  - The requirement of human immunodeficiency virus type 1 to generate numerous
      proteins from a single primary transcript is met largely by the use of suboptimal
      splicing to generate over 30 mRNAs. To ensure that appropriate quantities of each
      protein are produced, there must be a signal(s) that controls the efficiency with
      which any particular splice site in the RNA is used. To identify this control
      element(s) and to understand how it operates to generate the splicing pattern
      observed, we have initially focused on the control of splicing of the tat-rev
      intron, which spans the majority of the env open reading frame. Previous analysis
      indicated that a suboptimal branchpoint and polypyridimine tract in this intron
      contribute to its suboptimal splicing (A. Staffa and A. Cochrane, J. Virol.
      68:3071-3079, 1994). In this report, we identify two additional elements within
      the 3'-terminal exon, an exon-splicing enhancer (ESE) and an exon splicing
      silencer (ESS), that modulate the overall efficiency with which the 3' tat-rev
      splice site is utilized. Both elements are capable of functioning independently
      of one another. Furthermore, while both the ESE and ESS can function in a
      heterologous context, the function of the ESS is extremely sensitive to the
      sequence context into which it is placed. In conclusion, it would appear that the
      presence of a suboptimal branchpoint and a polypyrimidine tract as well as the
      ESE and ESS operate together to yield the balanced splicing of the tat-rev intron
      observed in vivo.

PMID- 7623852
TI  - Presence of exon splicing silencers within human immunodeficiency virus type 1
      tat exon 2 and tat-rev exon 3: evidence for inhibition mediated by cellular
      factors.
AB  - Human immunodeficiency virus type 1 (HIV-1) pre-mRNA splicing is regulated in
      order to maintain pools of unspliced and partially spliced viral RNAs as well as
      the appropriate levels of multiply spliced mRNAs during virus infection. We have
      previously described an element in tat exon 2 that negatively regulates splicing
      at the upstream tat 3' splice site 3 (B. A. Amendt, D. Hesslein, L.-J. Chang, and
      C. M. Stoltzfus, Mol. Cell. Biol. 14:3960-3970, 1994). In this study, we further
      defined the element to a 20-nucleotide (nt) region which spans the C-terminal vpr
      and N-terminal tat coding sequences. By analogy with exon splicing enhancer (ESE)
      elements, we have termed this element an exon splicing silencer (ESS). We show
      evidence for another negative cis-acting region within tat-rev exon 3 of HIV-1
      RNA that has sequence motifs in common with a 20-nt ESS element in tat exon 2.
      This sequence is juxtaposed to a purine-rich ESE element to form a bipartite
      element regulating splicing at the upstream tat-rev 3' splice site. Inhibition of
      the splicing of substrates containing the ESS element in tat exon 2 occurs at an
      early stage of spliceosome assembly. The inhibition of splicing mediated by the
      ESS can be specifically abrogated by the addition of competitor RNA. Our results
      suggest that HIV-1 RNA splicing is regulated by cellular factors that bind to
      positive and negative cis elements in tat exon 2 and tat-rev exon 3.

PMID- 7623853
TI  - A soluble form of Wnt-1 protein with mitogenic activity on mammary epithelial
      cells.
AB  - The proto-oncogene Wnt-1 plays an essential role in fetal brain development and
      causes hyperplasia and tumorigenesis when activated ectopically in the mouse
      mammary gland. When expressed in certain mammary epithelial cell lines, the gene
      causes morphological transformation and excess cell proliferation at confluence.
      Like other members of the mammalian Wnt family, Wnt-1 encodes secretory
      glycoproteins which have been detected in association with the extracellular
      matrix or cell surface but which have not previously been found in a soluble or
      biologically active form. We show here that conditioned medium harvested from a
      mammary cell line expressing Wnt-1 contains soluble Wnt-1 protein and induces
      mitogenesis and transformation of mammary target cells. By immunodepletion of
      medium containing epitope-tagged Wnt-1, we show that at least 60% of this
      activity is specifically dependent on Wnt-1 protein. These results provide the
      first demonstration that a mammalian Wnt protein can act as a diffusible
      extracellular signaling factor.

PMID- 7623854
TI  - Identification of target genes for the Ewing's sarcoma EWS/FLI fusion protein by
      representational difference analysis.
AB  - The EWS/FLI-1 fusion gene results from the 11;22 chromosomal translocation in
      Ewing's sarcoma. The product of the gene is one of a growing number of
      structurally altered transcription factors implicated in oncogenesis. We have
      employed a subtractive cloning strategy of representational difference analysis
      in conjunction with a model transformation system to identify genes transcribed
      in response to EWS/FLI. We have characterized eight transcripts that are
      dependent on EWS/FLI for expression and two transcripts that are repressed in
      response to EWS/FLI. Three of the former were identified by sequence analysis as
      stromelysin 1, a murine homolog of cytochrome P-450 F1 and cytokeratin 15.
      Stromelysin 1 is induced rapidly after expression of EWS/FLI, suggesting that the
      stromelysin 1 gene may be a direct target gene of EWS/FLI. These results
      demonstrate that expression of EWS/FLI leads to significant changes in the
      transcription of specific genes and that these effects are at least partially
      distinct from those caused by expression of germ line FLI-1. The representational
      difference analysis technique can potentially be applied to investigate
      transformation pathways activated by a broad array of genes in different tumor
      systems.

PMID- 7623855
TI  - The yeast Mcm1 protein is regulated posttranscriptionally by the flux of
      glycolysis.
AB  - Mcm1 is a multifunctional protein which plays a role both in the initiation of
      DNA replication and in the transcriptional regulation of diverse genes in
      Saccharomyces cerevisiae. The mcm1-1 mutation results in instability of
      minichromosomes and alpha-specific sterility. Second-site suppressors that
      restore minichromosome stability but not fertility to the mcm1-1 mutant were
      isolated. Two of the suppressors, pgm1-1 and pgm1-2, are mutant alleles of PGM1
      which encodes a glycolytic enzyme, phosphoglycerate mutase. We show that the pgm1
      1 mutation suppresses the minichromosome maintenance (Mcm) defect by increasing
      the protein activity or level of Mcm1-1 posttranscriptionally. This increase in
      the intracellular Mcm1-1 activity is sufficient to suppress the Mcm defect but
      only minimally suppresses the mating defect. Mutations in genes encoding other
      glycolytic enzymes, such as eno2::URA3, can also suppress the Mcm phenotype of
      mcm1-1. Suppression by these glycolytic enzyme mutations correlates with a
      reduced rate of glycolysis rather than a reduced rate of cell growth. This study
      suggests that in response to changes in their nutritional states yeast cells may
      attain homeostasis by modulating the activity of global regulators like Mcm1,
      which plays a central role in the regulation of energy-expensive anabolic
      processes.

PMID- 7623856
TI  - Dependence of globin gene expression in mouse erythroleukemia cells on the NF-E2
      heterodimer.
AB  - High-level, tissue-specific expression of the beta-globin genes requires the
      presence of an upstream locus control region (LCR). The overall enhancer activity
      of the beta-globin complex LCR (beta-LCR) is dependent on the integrity of the
      tandem NF-E2 sites of HS-2. The NF-E2 protein which binds these sites is a
      heterodimeric basic leucine zipper protein composed of a tissue-specific subunit,
      p45 NF-E2, and a smaller subunit, p18 NF-E2, that is widely expressed. In these
      studies, we sought to investigate the role of NF-E2 in globin expression. We show
      that expression of a dominant-negative mutant p18 greatly reduces the amount of
      functional NF-E2 complex in the cell. Reduced levels of both alpha- and beta
      globin were associated with the lower levels of NF-E2 activity in this cell line.
      Globin expression was fully restored upon the introduction of a tethered p45-p18
      heterodimer. We also examined CB3 cells, a mouse erythroleukemia (MEL) cell line
      that does not express endogenous p45 NF-E2, and demonstrated that the restoration
      of globin gene expression was dependent upon the levels of expressed tethered NF
      E2 heterodimer. Results of DNase I hypersensitivity mapping and in vivo
      footprinting assays showed no detectable chromatin alterations in beta-LCR HS-2
      due to loss of NF-E2. Finally, we examined the specificity of NF-E2 for globin
      gene expression in MEL cells. These experiments indicate a critical role for the
      amino-terminal domain of p45 NF-E2 and show that a related protein, LCRF1, is
      unable to restore globin gene expression in p45 NF-E2-deficient cells. From these
      results, we conclude that NF-E2 is specifically required for high level goblin
      gene expression in MEL cells.

PMID- 7623858
TI  - Clarification of the role of the Pro-X-Pro sequence in interleukin-5 receptor
      signal transduction.

PMID- 7623857
TI  - Stimulation of the mouse rRNA gene promoter by a distal spacer promoter.
AB  - We show that the mouse ribosomal DNA (rDNA) spacer promoter acts in vivo to
      stimulate transcription from a downstream rRNA gene promoter. This augmentation
      of mammalian RNA polymerase I transcription is observed in transient-transfection
      experiments with three different rodent cell lines, under noncompetitive as well
      as competitive transcription conditions, over a wide range of template
      concentrations, whether or not the enhancer repeats alone stimulate or repress
      expression from the downstream gene promoter. Stimulation of gene promoter
      transcription by the spacer promoter requires the rDNA enhancer sequences to be
      present between the spacer promoter and gene promoter and to be oriented as in
      native rDNA. Stimulation also requires that the spacer promoter be oriented
      toward the enhancer and gene promoter. However, stimulation does not correlate
      with transcription from the spacer promoter because the level of stimulation is
      not altered by either insertion of a functional mouse RNA polymerase I
      transcriptional terminator between the spacer promoter and enhancer or
      replacement with a much more active heterologous polymerase I promoter. Further
      analysis with a series of mutated spacer promoters indicates that the stimulatory
      activity does not reside in the major promoter domains but requires the central
      region of the promoter that has been correlated with enhancer responsiveness in
      vivo.

PMID- 7623859
TI  - Transcription of the E2F-1 gene is rendered cell cycle dependent by E2F DNA
      binding sites within its promoter.

PMID- 7623861
TI  - EC/US Workshop: Human Genetic Risks from Exposure to Chemicals, Focusing on the
      Feasibility of the Parallelogram Approach. Conference proceedings. Durham, North
      Carolina, 11-14 October 1993.

PMID- 7623860
TI  - EC/US workshop report: assessment of genetic risks associated with exposure to
      ethylene oxide, acrylamide, 1,3-butadiene and cyclophosphamide.
AB  - The EC/US Workshop on Risk Assessment: 'Human Genetic Risks from Exposure to
      Chemicals, Focusing on the Feasibility of a Parallelogram Approach' had as its
      main objective the identification of the methodology, data requirements and
      mechanistic research to understand the human health impact of germ cell mutagens.
      Specifically, it represented an evaluation of current knowledge and the
      identification of future research needs for a more precise assessment of human
      genetic risks from exposure to mutagenic chemicals. Four chemicals were selected
      for review at the Workshop and in this Special Issue: ethylene oxide, 1,3
      butadiene, acrylamide, and cyclophosphamide. The first three are important
      industrial chemicals with substantial use worldwide and, therefore, considerable
      potential for human exposure. The fourth, cyclophosphamide, is a commonly used
      cancer chemotherapeutic agent. This Special Issue contains the major scientific
      reports from the workshop. These include four Introductory Papers (on the
      parallelogram concept, alternative genetic risk assessment approaches, regulatory
      data needs, and the research background for risk assessment of ethylene oxide),
      four Working Group Reports on the specific compounds mentioned above and,
      finally, three Crosscutting Papers pertinent to the issue of germ-line
      mutagenesis and genetic risk estimation.

PMID- 7623862
TI  - 1,3-Butadiene working group report.
AB  - During the Workshop in North Carolina, the in vivo metabolism, adduct formation
      and genotoxicity data available from rodent and human exposure to 1,3-butadiente
      (BD) were reviewed and they are summarized in the present report. BD is
      metabolized by cytochrome P-450-dependent monoxygenases to the primary metabolite
      1,2-epoxybutene-3 (epoxybutene, EB). EB is subjected to further metabolism:
      oxidation to 1,2:3,4-diepoxybutane (DEB), hydrolysis to 3-butene-1,2-diol and
      conjugation to glutathione. The first pathway seems to prevail in mice while the
      latter is characteristic for rats and possibly for humans. Species differences
      exist in adduct formation of the monoepoxide to hemoglobin, for which the
      following pattern has been found: mice > rats > humans. Genotoxity of BD was
      found in mice with all applied tests; however, negative results were obtained in
      rats. In exposed humans, the cytogenetic studies in peripheral blood lymphocytes
      did not show genotoxic effects, although one report described elevated hprt
      variant levels in peripheral blood lymphocytes of exposed workers. It was
      concluded that the presently available data are insufficient for the application
      of the parallelogram model to estimate genetic risk for humans. As an alternative
      approach, a tentative estimate of the doubling dose for induction of hprt
      mutations in somatic cells of mice and men was performed and the calculated
      values were surprisingly similar, i.e. 9000 ppmh. However, this estimate is
      burdened with a number of caveats which were discussed in detail. The working
      group identified a series of urgent research needs to provide the appropriate
      data for the application of the parallelogram model, such as identification of
      metabolic pathways in different rodent species and humans, metabolic studies in
      mice, rats and humans considering metabolic polymorphisms, studies of adducts to
      DNA and hemoglobin especially of DEB and other butadiene metabolites in rodents
      and humans, studies of mutational spectra (mutational fingerprinting) in somatic
      and germinal cells, confirmation of the human hprt mutation data, conformation of
      the rodent malformation data, dose-response studies in rodent germ cell tests and
      studies on repair kinetics of mono-adducts induced by EB as opposed to repair of
      cross-links produced by DEB. Finally, it was suggested that the original
      parallelogram consisting of data from somatic cell studies in rodents and humans
      plus studies of heritable effects in rodents to extrapolate to germ cell risk for
      humans should be supplemented with studies in sperm of experimental animals and
      exposed men.

PMID- 7623863
TI  - Cyclophosphamide: review of its mutagenicity for an assessment of potential germ
      cell risks.
AB  - Cyclophosphamide (CP) is used to treat a wide range of neoplastic diseases as
      well as some non-malignant ones such as rheumatoid arthritis. It is also used as
      an immunosuppressive agent prior to organ transplantation. CP is, however, a
      known carcinogen in humans and produces secondary tumors. There is little
      absorption either orally or intravenously and 10% of the drug is excreted
      unchanged. CP is activated by hepatic mixed function oxidases and metabolites are
      delivered to neoplastic cells via the bloodstream. Phosphoramide mustard is
      thought to be the major anti-neoplastic metabolite of CP while acrolein, which is
      highly toxic and is produced in equimolar amounts, is thought to be responsible
      for most of the toxic side effects. DNA adducts have been formed after CP
      treatment in a variety of in vitro systems as well as in rats and mice using 3H
      labeled CP. 32P-postlabeling techniques have also been used in mice. However,
      monitoring of adducts in humans has not yet been carried out. CP has also been
      shown to induce unscheduled DNA synthesis in a human cell line. CP has produced
      mutations in base-pair substituting strains of Salmonella tryphimurium in the
      presence of metabolic activation, but it has been shown to be negative in the E.
      coli chromotest. It has also been shown to be positive in Saccharomyces
      cerevisiae in D7 strain for many endpoints but negative in D62.M for
      aneuploidy/malsegregation. It has produced positive responses in Drosophila
      melanogaster for various endpoints and in Anopheles stephensi. In somatic cells,
      CP has been shown to produce gene mutations, chromosome aberrations, micronuclei
      and sister chromatid exchanges in a variety of cultured cells in the presence of
      metabolic activation as well as sister chromatid exchanges without metabolic
      activation. It has also produced chromosome damage and micronuclei in rats, mice
      and Chinese hamsters, and gene mutations in the mouse spot test and in the
      transgenic lacZ construct of Muta Mouse. Increases in chromosome damage and gene
      mutations have been found in the peripheral blood lymphocytes of nurses,
      pharmacists and female workers occupationally exposured to CP during its
      production or distribution. Chromosome aberrations, sister chromatid exchanges
      and gene mutations have been observed in somatic cells of patients treated
      therapeutically with CP. In general, there is a maximum dose and an optimum time
      for the detection of genetic effects because the toxicity associated with high
      doses of CP will affect cell division. In germ cells, CP has been shown to induce
      genetic damage in mice, rats and hamsters although the vast majority of such
      studies have used male mice.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7623864
TI  - Assessment of heritable mutations--the parallelogram approach.

PMID- 7623865
TI  - DNA damage and repair in somatic and germ cells in vivo.
AB  - Alkylation-induced germ cell mutagenesis in the mouse versus Drosophila is
      compared based on data from forward mutation assays (specific-locus tests in the
      mouse and in Drosophila and multiple-locus assays in the latter species) but not
      including assays for structural chromosome aberrations. To facilitate comparisons
      between mouse and Drosophila, forward mutation test results have been grouped
      into three categories. Representatives of the first category are MMS (methyl
      methanesulfonate) and EO (ethylene oxide), alkylating agents with a high s value
      which predominantly react with ring nitrogens in DNA. ENU (N-ethyl-N
      nitrosourea), MNU (N-methyl-N-nitrosourea), PRC (procarbazine), DEN (N
      nitrosodiethylamine), and DMN (N-nitrosodimethylamine) belong to the second
      category. These agents have in common a considerable ability for modification at
      oxygens in DNA. Cross-linking agents (melphalan, chlorambucil,
      hexamethylphosphoramide) form the third category. The most unexpected, but
      encouraging outcome of this study is the identification of common features for
      three vastly different experimental indicators of genotoxicity: hereditary damage
      in Drosophila males, genetic damage in male mice, and tumors (TD50 estimates) in
      rodents. Based on the above three category classification scheme the following
      tentative conclusions are drawn. Monofunctional agents belonging to category 1,
      typified by MMS and EO, display genotoxic effects in male germ cell stages that
      have passed meiotic division. This phenomenon seems to be the consequence of a
      repair deficiency during spermiogenesis for a period of 3-4 days in Drosophila
      and 14 days in the mouse. We suggest that the reason for the high resistance of
      premeiotic stages, and the generally high TD50 estimates observed for this class
      in rodents, is the efficient error-free repair of N-alkylation damage. If we
      accept this hypothesis, then the increased carcinogenic potential in rodents,
      seen when comparing category 2 (ENU-type mutagens) to category 1 (MMS-type
      mutagens), along with the ability of category 2 genotoxins to induce genetic
      damage in premeiotic stages, must presumably be due to their enhanced ability for
      alkylations at oxygens in DNA; it is this property that actually distinguishes
      the two groups from each other. In contrast to category 1, examination of class 2
      genotoxins (ENU and DEN) in premeiotic cells of Drosophila gave no indication for
      a significant role of germinal selection, and also removal by DNA repair was less
      dramatic compared to MMS. Thus category 2 mutagens are expected to display
      activity in a wide range of both post- and premeiotic germ cell stages. A number
      of these agents have been demonstrated to be among the most potent carcinogens in
      rodents.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7623866
TI  - The rodent dominant lethal assay: a proposed format for data presentation that
      alerts to pseudo-dominant lethal effects.
AB  - The rodent dominant lethal (DL) germ cell mutagenicity assay is the primary test
      for possible human germ cell mutagens. As such, it occupies a critical regulatory
      position. DL assay data are often difficult to assess because of the quantity of
      data involved, and because several related assay parameters require to be
      considered simultaneously. To reduce this difficulty a schematic method of data
      presentation is proposed and illustrated. This method enables the most pertinent
      assay data and parameters to be viewed and considered simultaneously. Using this
      format of data presentation, existing DL studies on cyclophosphamide,
      methylnitrosourea, diethylhexylphthalate, divinyl sulphone, methyl
      methanesulphonate, 6-mercaptopurine and ethylenethiourea are re-analysed.

PMID- 7623867
TI  - Germ line specific factors in chemical mutagenesis.
AB  - Chemical mutagenesis test results have not revealed evidence of germ line
      specific mutagens. However, conventional assays have indicated that there are
      male-female differences in mutagenic response, as well as
      quantitative/qualitative differences in induced mutations which depend upon the
      particular cell stage exposed. Many factors inherent in the germ line can be
      speculated to influence chemical transport to, and interaction with, target cell
      populations to result in mutagenic outcomes. The level of uncertainty regarding
      the general operation of such factors, in combination with the limited
      availability of chemical test data designed to address comparative somatic and
      germ cell mutagenesis, leaves open the question of whether there are mutagens
      specifically affecting germ cells. This argues for a conservative approach to
      interpreting germ cell risk from somatic cell mutation analysis.

PMID- 7623868
TI  - International Commission for Protection Against Environmental Mutagens and
      Carcinogens. Genetic risk extrapolation from animal data to human disease. A
      Taskgroup Report. No. 00105.
AB  - This report describes a model for producing quantitative genetic risk assessments
      for human populations. The model is patterned after current methods used in
      cancer risk analysis. The risk to humans is expressed as the number of additional
      dominant genetic diseases added to the existing genetic burden, in the offspring
      of the exposed individuals.

PMID- 7623869
TI  - Information requirements and regulatory approaches for heritable genetic risk
      assessment and risk communication.
AB  - With the evolution of genetic toxicology as a scientific discipline and the
      formation of the Environmental Mutagen Society (EMS), much thought was given to
      the study of chemicals in the human environment for their mutagenic effects. The
      Society's goal was to promote scientific investigation and dissemination of
      information related to genetic toxicology. Subsequently, the concern for
      chemically induced genetic damage in human germ cells and its potential impact on
      genetic diseases was detailed in the Committee 17 Report (1975). With new
      information on the involvement of genetic alterations in disease and on the
      ramifications of possible effects of exposures to environmental mutagens, it is
      becoming increasingly necessary to again focus our attention on the assessment of
      heritable genetic effects. Clearly, strategies for communication of genetic
      hazard/risk assessments to exposed individuals and to those charged with
      regulating environmental agents need to be developed.

PMID- 7623870
TI  - The research background for risk assessment of ethylene oxide: aspects of dose.
AB  - Data for relationships between in vivo doses inferred from levels of hemoglobin
      (Hb) or DNA adducts and administered (by inhalation or injection) doses of
      ethylene oxide (EO) in mice, rats and humans are reviewed. At low absorbed doses
      or dose rates these relationships appear to be linear, whereas at higher dose
      rates deviations from linearity due to saturation kinetics of detoxification and
      of DNA repair as well as certain toxic effects have to be allowed for. If these
      factors are taken into consideration, a rather consistent picture is obtained for
      animal studies, with a variation by less than a factor 2 between estimates of
      adduct level increments or in vivo dose increments per unit of administered dose.
      Although the value for in vivo dose per unit of exposure dose (ppm-hour) in
      humans is uncertain because of unreliable data for the time-weighted average
      exposure level, the most likely value for this relationship, supported by data
      for ethene, agrees with data for the rodents. In the animal species testis doses
      are approximately one-half of the blood doses inferred from Hb adducts.

PMID- 7623871
TI  - Ethylene oxide: evaluation of genotoxicity data and an exploratory assessment of
      genetic risk.
AB  - A risk estimate of the heritable effects of ethylene oxide exposure, using the
      parallelogram approach, as suggested by Frits Sobels, is described. The approach
      is based on available data on the ethylene oxide-induced responses for the same
      genetic endpoint in somatic cells of both laboratory animals and humans, and for
      germ cell mutations in the same laboratory animal. Human germ cell effects are
      estimated. The available data sets for this approach were evaluated. We consider
      this as complementary to the genetic risk assessment carried out by U.S. EPA
      scientists, in which the risk from heritable (reciprocal) translocations induced
      by ethylene oxide was estimated. In the present study we restricted our
      assessment to dominant mutations. The sensitivity factor relating mouse to man
      was based on ethylene oxide-induced HPRT mutant frequencies in lymphocytes in
      vivo. From this comparison, it could be concluded that occupational exposure for
      1 year to 1 ppm ethylene oxide would lead to a risk of a dominantly inherited
      disease in the offspring of 4 x 10(-4) above the background level. The
      uncertainty interval of this figure is quite large (0.6-28) x 10(-4). The values
      are compatible with the existing estimates of the corresponding risk from
      exposure to low LET radiation when the genotoxic potency ratio of ethylene oxide
      and radiation is considered. This risk estimation approach has allowed us to
      identify additional data that are required for a more complete risk estimation of
      the heritable effects of ethylene oxide, or indeed any mutagenic chemical.

PMID- 7623872
TI  - Acrylamide: a review of its genotoxicity and an assessment of heritable genetic
      risk.
AB  - An updated review of the genotoxicity studies with acrylamide is provided. Then,
      using data from the studies generating quantitative information concerning
      heritability of genetic effects, an assessment of the heritable genetic risk
      presented by acrylamide is presented. The review offers a discussion of the
      reactions and possible mechanisms of genotoxic action by acrylamide and its
      epoxide metabolite glycidamide. Several genetic risk approaches are discussed,
      including the parallelogram, direct (actually a modified direct), and doubling
      dose approaches. Using data from the specific-locus and heritable translocation
      assays, the modified direct and doubling dose approaches are utilized to
      quantitate genetic risk. Exposures of male parents to acrylamide via inhalation,
      ingestion, and dermal routes are also quantitated. With these approaches and
      measurements and their underlying assumptions concerning extrapolation factors
      (including germ cell stage specificity, DNA repair variability, locus
      specificity), number of human loci associated with dominant disease alleles, and
      spontaneous mutation rates, an assessment of heritable genetic risk for humans is
      calculated for the three exposure scenarios. The calculated estimates for
      offspring from fathers exposed to acrylamide via drinking water are up to three
      offspring potentially affected with induced genetic disease per 10(8) offspring.
      Estimates for inhalation or dermal exposures suggest higher risks for induced
      genetic disease in offspring from fathers exposed in occupational settings.

PMID- 7623873
TI  - Induction of chromosome loss in Saccharomyces cerevisiae strain D61.M by selected
      benzimidazole compounds.
AB  - Twenty-two benzimidazole compounds were tested for induction of chromosome loss
      (CHRL) in the diploid yeast Saccharomyces cerevisiae strain D61.M. Six compounds
      tested positive for CHRL induction: mebendazole, albendazole, RS-9237-000,
      fenbendazole, 2-benzimidazolylacetonitrile, and thiabendazole. Mebendazole,
      albendazole, RS-9237-000, and fenbendazole were strongly positive only after
      modified testing media were used to enhance solubility. The compounds that tested
      negative for CHRL were 2-phenylbenzimidazole, 2-(2-pyridyl)benzimidazole,
      benzimidazole, 2-aminobenzimidazole, 2-amino-5,6-dimethylbenzimidazole, 2
      (aminomethyl)benzimidazole dihydrochloride hydrate, 5,6-dimethylbenzimidazole, 2
      guanidinobenzimidazole, 2-methylbenzimidazole, 2-(methylmercapto) benzimidazole,
      1-methyl-2-phenylbenzimidazole, 2-benzimidazolylurea, RS-65255-000, oxibendazole,
      and RS-95005-000. One chemical, cambendazole, tested negative or only marginally
      positive. Modified testing medium was also used to enhance the solubility of 2
      phenylbenzimidazole, oxibendazole, and RS-95005-000. Because no toxicity was
      observed with oxibendazole or RS-95005-000, the negative results obtained with
      these two compounds could not be considered definitive.

PMID- 7623874
TI  - Comparative studies by comet test and SCE analysis in human lymphocytes from 200
      healthy subjects.
AB  - The comet test (single cell gel electrophoresis, SCGE) appears to be a promising
      tool to estimate DNA damage at the single cell level and it provides information
      on the presence of damage among individual cells. Previously, we analyzed the
      degree of DNA damage in peripheral human lymphocytes from 100 healthy subjects
      living in Pisa (Italy) taking into account age, gender and smoking habit, and we
      also reported some results aiming at the assessment of the comet test (Betti el
      al., 1994). In addition, SCE analysis was carried out in order to compare the two
      endpoints. Because of the interesting results obtained, the present study was
      extended to 200 individuals, and data analyzed included information concerning
      number of cigarettes smoked a day, tar/cigarette and job. Data obtained confirmed
      that the SCGE is more sensitive than SCE in revealing smoking habit effects but
      comet induction did not seem to be related to the amount of cigarette tar
      inhaled. Moreover, sampling time was found to play a greater role in the comet
      assay as compared to SCE. Job position did not significantly influence SCE
      mean/subject or comet length mean/subject.

PMID- 7623875
TI  - DNA-protein crosslink formation in rat nasal epithelial cells by
      hexamethylphosphoramide and its correlation with formaldehyde production.
AB  - Hexamethylphosphoramide (HMPA) is an aprotic polar solvent and nasal carcinogen
      in rats. The metabolism of HMPA to formaldehyde, another nasal carcinogen in
      rats, was found to be approximately 6 times greater in microsomes from olfactory
      tissues than from respiratory tissues (isolated from both male and female rats).
      HMPA was shown to induce formation of DNA-protein crosslinks (DPXLS) in isolated
      rat nasal epithelial cells. Using a filter binding assay, we demonstrated that
      microsomal activation is necessary for HMPA-induced crosslink formation between
      plasmid DNA and calf thymus histones, presumably through metabolic N
      demethylation of HMPA and the formation of formaldehyde. Both formaldehyde
      production and DPXL formation were inhibited by pre-incubation of nasal mucosal
      extracts with metyrapone, an inhibitor of cytochrome P-450. Significant dose
      dependent increases in DPXL formation were observed in respiratory and olfactory
      epithelial cells exposed to > or = 0.5 and 1 mM HMPA, respectively, for 3 h at 37
      degrees C. This resulted in DPXL accumulation at 18-20% higher levels than
      untreated cells. Increases in DPXL formation in rat nasal epithelial cells
      cultured with 1 mM HMPA were inhibited by over 70% by co-administration of
      metyrapone. These data suggest that metabolic liberation of formaldehyde from
      HMPA is involved in the mechanism of HMPA-induced nasal carcinogenesis.
      Comparative studies showed formaldehyde to be more potent than HMPA in the
      induction of DPXL in nasal epithelium. However, induction of tumor formation
      after two years at 50 ppb HMPA and 6 ppm formaldehyde show the former to be
      active at several-fold lower concentrations. Therefore, other mechanisms are
      likely to be involved in HMPA nasal carcinogenesis.

PMID- 7623876
TI  - Determination of mutational spectrum of the pesticide, captan, with an improved
      set of Escherichia coli LacZ mutants.
AB  - The mutational spectrum of the fungicide, captan, was determined using a set of
      improved Escherichia coli lacZ mutants. Captan created mutations mostly at dA-dT
      sites (83%) with only 17% occurring at dG-dC sites. The hydrolysis products of
      captan do not appear to be mutagenic because samples of captan at different
      hydrolysis stages showed basically the same mutational spectra: 31% at AT --> CG
      transversions, 8% of GC --> AT transitions, 2% of GC --> CG transversions, 8% of
      GC --> TA transversions, 19% of AT --> TA transversions, and 32% of AT --> GC
      transitions. Prepared solutions of captan lost their mutational activity
      gradually over time, indicating that the rate of decrease in mutagenicity agreed
      with the kinetics of captan hydrolysis reported in other studies. Using the
      change in mutagenicity to predict degradation, the hydrolysis of captan in pH 7.0
      buffer was about three times faster than the hydrolysis carried out in pH 4.5
      buffer. To our knowledge, this is the first presentation of mutational spectrum
      of captan.

PMID- 7623877
TI  - Genotoxic effect of griseofulvin in somatic cells of Drosophila melanogaster.
AB  - Griseofulvin (GF), a carcinogenic spindle poison, was tested in two types of
      somatic-cell assays of Drosophila melanogaster, one of which detects the
      induction of DNA damage and the other mutation/mitotic recombination. In both
      assays, GF was fed to tester larvae and genetic endpoints examined after
      emergence. In the wing spot test, trans-heterozygous flies carrying mwh and flr3
      wing-hair mutations produced both significant and dose-dependent increases in the
      frequency of mwh single spots over the control level but no increase of twin
      spots. In the DNA repair test, double-mutant larvae carrying both mei-9(a)
      (excision repair-defective) and mei-41(D5) (postreplication repair-defective)
      mutations showed hypersensitivity to killing by GF compared with their DNA repair
      proficient counterparts, suggesting that GF caused potentially lethal DNA damages
      which were efficiently repaired by the DNA repair-proficient but not -defective
      larvae. These lines of evidence clearly demonstrate that GF is genotoxic in
      somatic cells of Drosophila. It is noted that (1) GF-fed larvae showed a
      developmental delay and (2) surviving adult flies had morphological abnormalities
      in their eyes and wings.

PMID- 7623878
TI  - A comparison of surgical and medical therapy for atrial septal defect in adults.
AB  - BACKGROUND: The surgical closure of an atrial septal defect is frequently
      recommended for patients over 40 years of age. However, the prognosis for such
      patients with unrepaired defects is largely unknown, and the outcome for patients
      operated on after the fourth decade of life has not yet been compared with that
      for medically treated patients in a controlled follow-up study. METHODS: In a
      retrospective study, we examined the clinical course of 179 consecutive patients
      with isolated atrial septal defects diagnosed after the age of 40. The 84
      patients (47 percent) who underwent surgical repair were compared with the 95
      patients (53 percent) who were treated medically. The mean (+/-SD) follow-up
      period was 8.9 +/- 5.2 years (range, 1 to 26). RESULTS: Multivariate analysis
      revealed that surgical closure of the defect significantly reduced mortality from
      all causes (relative risk, 0.31; 95 percent confidence interval, 0.11 to 0.85).
      The adjusted 10-year survival rate of surgically treated patients was 95 percent,
      as compared with 84 percent for the medically treated patients. In addition,
      surgical treatment prevented functional deterioration, as measured by the New
      York Heart Association class (relative risk, 0.21; 95 percent confidence
      interval, 0.08 to 0.55). However, the incidence of new atrial arrhythmias or of
      cerebrovascular insults in the two groups was not significantly different.
      CONCLUSIONS: The surgical repair of an atrial septal defect in patients over 40
      years of age, as compared with medical therapy, increases long-term survival and
      limits the deterioration of function due to heart failure. However, surgically
      treated patients should be followed closely for the onset of atrial arrhythmias
      so as to reduce the risk of thromboembolic complications.

PMID- 7623879
TI  - Resistance to penicillin and cephalosporin and mortality from severe pneumococcal
      pneumonia in Barcelona, Spain.
AB  - BACKGROUND: Penicillin-resistant strains of Streptococcus pneumoniae are now
      found worldwide, and strains with resistance to cephalosporin are being reported.
      The appropriate antibiotic therapy for pneumococcal pneumonia due to resistant
      strains remains controversial. METHODS: To examine the effect of resistance to
      penicillin and cephalosporin on mortality, we conducted a 10-year, prospective
      study in Barcelona of 504 adults with culture-proved pneumococcal pneumonia.
      RESULTS: Among the 504 patients, 145 (29 percent) had penicillin-resistant
      strains of S. pneumoniae (minimal inhibitory concentration [MIC] of penicillin G,
      0.12 to 4.0 micrograms per milliliter), and 31 patients (6 percent) had
      cephalosporin-resistant strains (MIC of ceftriaxone or cefotaxime, 1.0 to 4.0
      micrograms per milliliter). Mortality was 38 percent in patients with penicillin
      resistant strains, as compared with 24 percent in patients with penicillin
      sensitive strains (P = 0.001). However, after the exclusion of patients with
      polymicrobial pneumonia and adjustment for other predictors of mortality, the
      odds ratio for mortality in patients with penicillin-resistant strains was 1.0
      (95 percent confidence interval, 0.5 to 1.9; P = 0.84). Among patients treated
      with penicillin G or ampicillin, the mortality was 25 percent in the 24 with
      penicillin-resistant strains and 19 percent in the 126 with penicillin-sensitive
      strains (P = 0.51). Among patients treated with ceftriaxone or cefotaxime, the
      mortality was 22 percent in the 59 with penicillin-resistant strains and 25
      percent in the 127 with penicillin-sensitive strains (P = 0.64) The frequency of
      resistance to cephalosporin increased from 2 percent in 1984-1988 to 9 percent in
      1989-1993 (P = 0.002). Mortality was 26 percent in patients with cephalosporin
      resistant S. pneumoniae and 28 percent in patients with susceptible organisms (P
      = 0.89). Among patients treated with ceftriaxone or cefotaxime, mortality was 22
      percent in the 18 with cephalosporin-resistant strains and 24 percent in the 168
      with cephalosporin-sensitive organisms (P = 0.64). CONCLUSIONS: Current levels of
      resistance to penicillin and cephalosporin by S. pneumoniae are not associated
      with increased mortality in patients with pneumococcal pneumonia. Hence, these
      antibiotics remain the therapy of choice for this disease.

PMID- 7623880
TI  - The prevalence of drug-resistant Streptococcus pneumoniae in Atlanta.
AB  - BACKGROUND: Streptococcus pneumoniae is a major cause of illness, and the
      emergence of drug-resistant strains threatens to complicate the management of
      pneumococcal infections. We conducted a laboratory-based surveillance for drug
      resistant S. pneumoniae among patients with invasive pneumococcal infections in
      Atlanta. METHODS: From January through October 1994, pneumococcal isolates from
      431 patients with invasive disease in metropolitan Atlanta were serotyped and
      tested to determine their susceptibility to various antimicrobial agents.
      Susceptibility to the antimicrobial agents was defined according to guidelines
      established by the National Committee for Clinical Laboratory Standards. RESULTS:
      The annual incidence of invasive pneumococcal infection was 30 cases per 100,000
      population. Isolates from 25 percent of the patients were resistant to penicillin
      (7 percent were highly resistant), and isolates from 26 percent were resistant to
      trimethoprim-sulfamethoxazole (7 percent highly resistant). Fifteen percent of
      the isolates were resistant to erythromycin, 9 percent to cefotaxime (4 percent
      were highly resistant), and 25 percent to multiple drugs. Drug-resistant
      pneumococci were found in both children and adults. Children under six years of
      age were more likely than older children and adults to have isolates resistant to
      multiple drugs or cefotaxime. Whites were more likely than blacks to have
      invasive pneumococcal infections caused by drug-resistant organisms. Among white
      children younger than six years, 41 percent of the S. pneumoniae isolates were
      resistant to penicillin. CONCLUSIONS: Drug-resistant strains of S. pneumoniae are
      common among both children and adults in Atlanta. Although blacks had a higher
      incidence of invasive pneumococcal infections than whites, whites were more
      likely to be infected with a drug-resistant isolate. Control of drug-resistant
      pneumococci will require more judicious use of antimicrobial agents and wider use
      of the pneumococcal polysaccharide vaccine.

PMID- 7623881
TI  - Brief report: fatal hemorrhage in a patient with an acquired inhibitor of human
      thrombin.

PMID- 7623882
TI  - Images in clinical medicine. Diverticulitis.

PMID- 7623883
TI  - Beta-adrenergic bronchodilators.

PMID- 7623884
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 26-1995. A previously well, 29-year-old woman with a pathologic
      fracture of the femur.

PMID- 7623886
TI  - The pneumococcus at the gates.

PMID- 7623885
TI  - Surgical closure of atrial septal defect in adults.

PMID- 7623887
TI  - Treatment of tuberculosis in HIV-infected patients in Zaire.

PMID- 7623888
TI  - Treatment of tuberculosis in HIV-infected patients in Zaire.

PMID- 7623889
TI  - Clinical problem-solving: we blew it.

PMID- 7623890
TI  - Clinical problem-solving: we blew it.

PMID- 7623891
TI  - Nitric oxide and AIDS dementia.

PMID- 7623892
TI  - Nitric oxide and motor neuron disease.

PMID- 7623893
TI  - Jumping genes.

PMID- 7623894
TI  - Jumping genes.

PMID- 7623895
TI  - The APC gene in Turcot's syndrome.

PMID- 7623896
TI  - Case 12-1995: acute postinfectious glomerulonephritis.

PMID- 7623897
TI  - Viable embryos from injection of round spermatids into oocytes.

PMID- 7623898
TI  - Saddle nose.

PMID- 7623899
TI  - Still more on breast implants and connective-tissue diseases.

PMID- 7623900
TI  - Medicine, death, and the criminal law.

PMID- 7623901
TI  - Methotrexate and misoprostol to terminate early pregnancy.
AB  - BACKGROUND: Although medical termination of pregnancy is available in Europe and
      China as an alternative to surgical termination, political and social factors
      have blocked medical approaches to pregnancy termination in the United States.
      Methotrexate, which is toxic to trophoblastic tissue, has been used safely to
      treat unruptured ectopic pregnancies. This report describes the use of a single
      low dose of methotrexate followed by intravaginal misoprostol for the medical
      termination of early pregnancy. METHODS: Women seeking termination of pregnancy
      were selected for this study on the basis of their good general health, emotional
      stability, and a pregnancy of 63 days or less in duration. Each woman received an
      intramuscular dose of methotrexate (50 mg per square meter of body-surface area).
      Five to seven days later, 800 micrograms of misoprostol was administered
      intravaginally. If abortion did not occur after seven days, the women was offered
      a second dose of misoprostol or vacuum aspiration. Successful abortion was
      defined as a complete termination of pregnancy within seven days after the first
      or second administration of misoprostol. RESULTS: A total of 171 of the 178 women
      enrolled in the study (96 percent) had successful medical abortions. Twenty-five
      women (14 percent) did not have an abortion after the first dose of misoprostol
      and received a second dose. Eighteen subsequently had complete abortions, but
      seven required suction curettage. In all seven women who required suction
      curettage, there was histologic evidence of disruption in the conceptus. No
      important side effects or complications were noted. CONCLUSIONS: The combination
      of methotrexate and misoprostol represents a safe and effective alternative to
      invasive methods for the termination of early pregnancy.

PMID- 7623902
TI  - Efficacy of metformin in patients with non-insulin-dependent diabetes mellitus.
      The Multicenter Metformin Study Group.
AB  - BACKGROUND: Sulfonylurea drugs have been the only oral therapy available for
      patients with non-insulin-dependent diabetes mellitus (NIDDM) in the United
      States. Recently, however, metformin has been approved for the treatment of
      NIDDM. METHODS: We performed two large, randomized, parallel-group, double-blind,
      controlled studies in which metformin or another treatment was given for 29 weeks
      to moderately obese patients with NIDDM whose diabetes was inadequately
      controlled by diet (protocol 1: metformin vs. placebo; 289 patients), or diet
      plus glyburide (protocol 2: metformin and glyburide vs. metformin vs. glyburide;
      632 patients). To determine efficacy we measured plasma glucose (while the
      patients were fasting and after the oral administration of glucose), lactate,
      lipids, insulin, and glycosylated hemoglobin before, during, and at the end of
      the study. RESULTS: In protocol 1, at the end of the study the 143 patients in
      the metformin group, as compared with the 146 patients in the placebo group, had
      lower mean (+/- SE) fasting plasma glucose concentrations (189 +/- 5 vs. 244 +/-
      6 mg per deciliter [10.6 +/- 0.3 vs. 13.7 +/- 0.3 mmol per liter], P < 0.001) and
      glycosylated hemoglobin values (7.1 +/- 0.1 percent vs. 8.6 +/- 0.2 percent, P <
      0.001). In protocol 2, the 213 patients given metformin and glyburide, as
      compared with the 210 patients treated with glyburide alone, had lower mean
      fasting plasma glucose concentrations (187 +/- 4 vs. 261 +/- 4 mg per deciliter
      [10.5 +/- 0.2 vs. 14.6 +/- 0.2 mmol per liter], P < 0.001) and glycosylated
      hemoglobin values (7.1 +/- 0.1 percent vs. 8.7 +/- 0.1 percent, P < 0.001). The
      effect of metformin alone was similar to that of glyburide alone. Eighteen
      percent of the patients given metformin and glyburide had symptoms compatible
      with hypoglycemia, as compared with 3 percent in the glyburide group and 2
      percent in the metformin group. In both protocols the patients given metformin
      had statistically significant decreases in plasma total and low-density
      lipoprotein cholesterol and triglyceride concentrations, whereas the values in
      the respective control groups did not change. There were no significant changes
      in fasting plasma lactate concentrations in any of the groups. CONCLUSIONS:
      Metformin monotherapy and combination therapy with metformin and sulfonylurea are
      well tolerated and improve glycemic control and lipid concentrations in patients
      with NIDDM whose diabetes is poorly controlled with diet or sulfonylurea therapy
      alone.

PMID- 7623903
TI  - Metabolic effects of metformin in non-insulin-dependent diabetes mellitus.
AB  - BACKGROUND: The metabolic effects and mechanism of action of metformin are still
      poorly understood, despite the fact that it has been used to treat patients with
      non-insulin-dependent diabetes mellitus (NIDDM) for more than 30 years. METHODS:
      In 10 obese patients with NIDDM, we used a combination of isotope dilution,
      indirect calorimetry, bioimpedance, and tissue-balance techniques to assess the
      effects of metformin on systemic lactate, glucose, and free-fatty-acid turnover;
      lactate oxidation and the conversion of lactate to glucose; skeletal-muscle
      glucose and lactate metabolism; body composition; and energy expenditure before
      and after four months of treatment. RESULTS: Metformin treatment decreased the
      mean (+/- SD) glycosylated hemoglobin value from 13.2 +/- 2.2 percent to 10.5 +/-
      1.6 percent (P < 0.001) and reduced fasting plasma glucose concentrations from
      220 +/- 41 to 155 +/- 28 mg per deciliter (12.2 +/- 0.7 to 8.6 +/- 0.5 mmol per
      liter) (P < 0.001). Although resting energy expenditure did not change, the
      patients lost 2.7 +/- 1.3 kg of weight (P < 0.001), 88 percent of which was
      adipose tissue. The mean (+/- SE) rate of plasma glucose turnover (hepatic
      glucose output and systemic glucose disposal) decreased from 2.8 +/- 0.2 to 2.0
      +/- 0.2 mg per kilogram of body weight per minute (15.3 +/- 0.9 to 10.8 +/- 0.9
      mumol per kilogram per minute) (P < 0.001), as a result of a decrease in hepatic
      glucose output; systemic glucose clearance did not change. The rate of conversion
      of lactate to glucose (gluconeogenesis) decreased by 37 percent (P < 0.001),
      whereas lactate oxidation increased by 25 percent (P < 0.001). There were no
      changes in the plasma lactate concentration, plasma lactate turnover, muscle
      lactate release, plasma free-fatty-acid turnover, or uptake of glucose by muscle.
      CONCLUSIONS: Metformin acts primarily by decreasing hepatic glucose output,
      largely by inhibiting gluconeogenesis. It also seems to induce weight loss,
      preferentially involving adipose tissue.

PMID- 7623904
TI  - Sclerotherapy with or without octreotide for acute variceal bleeding.
AB  - BACKGROUND: Sclerotherapy is considered the most effective way to stop bleeding
      from esophageal varices, but acute variceal bleeding is still associated with a
      high risk of rebleeding and death. We compared sclerotherapy alone with
      sclerotherapy and octreotide to control acute variceal bleeding and prevent early
      rebleeding in patients with cirrhosis. METHODS: In a double-blind, prospective
      trial, 199 patients with cirrhosis and acute variceal bleeding who underwent
      emergency sclerotherapy were randomly assigned to receive a continuous infusion
      of octreotide (25 micrograms per hour) or placebo for five days. The primary
      outcome measure was survival without rebleeding five days after sclerotherapy.
      RESULTS: After five days, the proportion of patients who had survived without
      rebleeding was higher in the octreotide group (85 of 98 patients, or 87 percent)
      than in the placebo group (72 of 101, or 71 percent; 95 percent confidence
      interval for the difference, 4 to 27 percent; P = 0.009). The mean number of
      units of blood transfused within the first 24 hours after sclerotherapy was lower
      in the octreotide group (1.2 units; range, 0 to 7) than in the placebo group (2.0
      units; range, 0 to 10; P = 0.006). A logistic-regression analysis showed that the
      treatment assignment (P = 0.003) and the number of blood units transfused before
      any other treatment was undertaken (P = 0.002) were the only two variables
      independently associated with survival without rebleeding. After adjustment for
      base-line differences between the two groups, the odds ratio for treatment
      failure in the placebo group, as compared with the octreotide group, was 3.3 (95
      percent confidence interval, 1.5 to 7.3). The mean (+/- SD) 15-day cumulative
      survival rate (estimated by the Kaplan-Meier method) was 88 +/- 12 percent in
      both groups. Side effects were minor, and their incidence was similar in the two
      groups. CONCLUSIONS: In patients with cirrhosis, the combination of sclerotherapy
      and octreotide is more effective than sclerotherapy alone in controlling acute
      variceal bleeding, but there is no difference between the overall mortality rates
      associated with the two approaches to treatment.

PMID- 7623905
TI  - Brief report: meningitis due to iatrogenic BCG infection in two immunocompromised
      children.

PMID- 7623906
TI  - Images in clinical medicine. Rhinocerebral mucormycosis.

PMID- 7623907
TI  - Regional variation across the United States in the management of acute myocardial
      infarction. GUSTO-1 Investigators. Global Utilization of Streptokinase and Tissue
      Plasminogen Activator for Occluded Coronary Arteries.
AB  - BACKGROUND: Differences in the management of acute myocardial infarction have
      been reported among countries, but few studies have investigated this issue in
      regions of the United States. METHODS: We compared the management of acute
      myocardial infarction among census regions across the United States, using data
      from the first Global Utilization of Streptokinase and Tissue Plasminogen
      Activator for Occluded Coronary Arteries trial (GUSTO-1) comprising 21,772
      patients, and from the American Hospital Association. RESULTS: We found
      substantial regional variation in the management of acute myocardial infarction
      in the United States. Beta-blockers (prescribed for a range of 55 to 81 percent
      of patients in the various regions), nitrates (prescribed for 61 to 77 percent),
      and angiotensin-converting-enzyme inhibitors (prescribed for 18 to 23 percent)
      were used most often in New England, whereas calcium-channel blockers (31 to 42
      percent) and lidocaine (14 to 43 percent) were used least often there. Similarly,
      the proportion of patients undergoing various cardiac procedures differed among
      regions (range for angiography, 52 to 81 percent of patients; angioplasty, 22 to
      35 percent; and coronary-artery bypass surgery, 9 to 17 percent) and was lowest
      in New England. The regional use of cardiac procedures was closely related to
      their availability, except in New England. After the analysis was adjusted for
      clinical and hospital variables, patients in New England were found to be less
      likely to undergo angiography than patients in the other regions (odds ratio,
      0.37; 95 percent confidence interval, 0.32 to 0.42). There was no apparent
      relation between the use of cardiac procedures and rates of recurrent infarction
      or death at 30 days or 1 year. CONCLUSIONS: There is substantial regional
      variation in the use of cardiac medications and procedures to manage acute
      myocardial infarction in the United States. The use and availability of cardiac
      procedures are closely related. The management of acute myocardial infarction in
      New England is atypical in that the relatively limited availability of cardiac
      procedures does not account for their relatively low use in that region.

PMID- 7623908
TI  - Variation in the use of cardiac procedures after acute myocardial infarction.
AB  - BACKGROUND: There are large geographic differences in the frequency with which
      coronary angiography and revascularization are performed. We attempted to assess
      whether differences in case mix or in the treatment of specific groups of
      patients may explain this variability. We also assessed the consequences of
      various patterns of treatment. METHODS: We studied patients covered by Medicare
      who were 65 to 79 years of age and were admitted to 478 hospitals with acute
      myocardial infarctions during 1990 in New York (1852 patients), where the rate of
      use of cardiac procedures is low, and in Texas (1837 patients), where the rate of
      use of such procedures is high. We compared the patterns of treatment of
      clinically similar groups of patients in the two states. We also compared
      mortality rates and measures of the health-related quality of life. RESULTS:
      Coronary angiography was performed more often in Texas than in New York (45
      percent vs. 30 percent, P < 0.001). The frequency of use in Texas was
      significantly higher than that in New York for all the clinical subgroups of
      patients analyzed except those at greatest risk for reinfarction. Over a two-year
      period, the adjusted likelihood of death was lower in New York than in Texas
      (hazard ratio, 0.87; 95 percent confidence interval, 0.78 to 0.98). Patients from
      Texas were 41 percent more likely to report angina (P = 0.002) and 62 percent
      more likely to say they could not perform activities requiring energy expenditure
      of 5 or more metabolic equivalents than patients from New York approximately two
      years after infarction (P < 0.001). CONCLUSIONS: Physicians in Texas were more
      likely to perform angiography than physicians in New York for patients whose
      conditions allowed more discretion in the use of cardiac procedures. On average,
      there appears to be no advantage with respect to mortality or health-related
      quality of life to performing the procedures at the higher rate used in Texas.

PMID- 7623909
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 27-1995. A 29-month-old girl with worsening ataxia, nystagmus,
      and subsequent opsoclonus and myoclonus.

PMID- 7623910
TI  - Metformin.

PMID- 7623911
TI  - Regional variation in medical care.

PMID- 7623912
TI  - Discovering new memories in psychotherapy--childhood revisited, fantasy, or both?

PMID- 7623913
TI  - Additional corrections: interferon for hemangiomas of infancy.

PMID- 7623915
TI  - Adjuvant chemotherapy in breast cancer.

PMID- 7623914
TI  - Adjuvant chemotherapy in breast cancer.

PMID- 7623916
TI  - Adjuvant chemotherapy in breast cancer.

PMID- 7623917
TI  - Deferiprone in iron overload.

PMID- 7623918
TI  - Deferiprone in iron overload.

PMID- 7623919
TI  - Protection against tetanus.

PMID- 7623920
TI  - Methotrexate for Crohn's disease.

PMID- 7623921
TI  - Maternal-fetal transfer of octreotide.

PMID- 7623922
TI  - DNA on trial.

PMID- 7623924
TI  - Plasma esterase activities in rats fed diets containing either glucose or
      fructose.

PMID- 7623923
TI  - Study on the migration phenomena of selected metals in canned fruits during long
      storage.
AB  - Experimental studies were conducted on the migration of Fe, Sn, Ca, and Mg in
      canned fruits: black currant, cherry and strawberry. Three-piece-cans had been
      protected with different coatings and technics. Cans of 31 capacity with fruits
      were stored in ambient temperature (ca 20 degrees C) during 60 weeks. There was
      stated increasing dependence of storage time on concentration of Fe and Sn in
      cans. Contents of Ca and Mg in this time systematically decreased in cans due to
      adsorption process of these metals on internal coatings. Migration rate of Fe and
      Sn, as well as migration trends of Ca and Mg (adsorption process) are shown on
      figures. There are great differences among migration of Fe, Sn and migration
      trends of Ca and Mg. Both these phenomena are disadvantageous for quality of
      canned fruits.

PMID- 7623925
TI  - Selenium content of infant formulas and estimation of the intake of bottle fed
      infants.

PMID- 7623926
TI  - Study of the antioxidative effects of thyme, sage, juniper and oregano.

PMID- 7623927
TI  - [Dyspareunia].

PMID- 7623929
TI  - [Yeast infections in patients with immunologic disorders].

PMID- 7623928
TI  - [Risk of breast carcinoma caused by 'the pill' should not be exaggerated].

PMID- 7623930
TI  - [Treatment and prevention of generalized mycoses].

PMID- 7623932
TI  - [Generalized histoplasmosis due to endogenous reactivation of a latent infection
      in an HIV-seronegative man].
AB  - A 63-year-old, Dutch, HIV-seronegative man presented with anal pain and itch of 6
      months' duration, a perianal ulcer and a solitary colon ulcer. Crohn's disease
      was suspected; the patient was treated with corticosteroids, but later died.
      Autopsy revealed disseminated histoplasmosis, a fungal disease rare in the
      Netherlands. The patient had visited Honduras. This case report illustrates that
      disseminated histoplasmosis may mimic Crohn's disease leading to a delay in the
      diagnosis.

PMID- 7623931
TI  - [Intra-anal application of isosorbide dinitrate in chronic anal fissure].
AB  - OBJECTIVE: To evaluate the effect of intra-anal application of isosorbide
      dinitrate on the healing rate of chronic anal fissure. DESIGN: Prospective,
      descriptive. SETTING: Outpatient clinic of the department of Surgery, University
      Hospital Dijkzigt, Rotterdam. METHOD: Sixteen patients with chronic (more than
      three months' duration) anal fissure were treated by intra-anal application of
      isosorbide dinitrate ointment every 3 hours, except during the night. The maximal
      duration of therapy was 12 weeks. Every three weeks the following aspects were
      investigated: clinical symptoms, side-effects and fissure healing. RESULTS: All
      patients experienced mild and transient headache shortly after the beginning of
      the treatment. At three weeks the fissure-related pain was resolved in all
      patients. At 6, 9 and 12 weeks the fissure was completely healed in 9, 11 and 15
      patients respectively. CONCLUSION: The majority of chronic anal fissures can be
      treated effectively by local application of isosorbide dinitrate. This new and
      simple treatment modality appears to be an attractive alternative to the
      currently available surgical procedures.

PMID- 7623933
TI  - ['The pill' as center of attention?].

PMID- 7623934
TI  - [Developments in jurisprudence in relation to life's end].

PMID- 7623935
TI  - [Hypokalemic periodic paralysis as the sole manifestation of hyperthyroidism].

PMID- 7623936
TI  - [Patient characteristics with predictive significance for 'blocked bed' problems
      in the neurological department of a general hospital].

PMID- 7623937
TI  - [Current treatment of Hirschsprung disease: the end of the stoma era].

PMID- 7623938
TI  - [Preoperative examination].

PMID- 7623939
TI  - [Familial forms of frontotemporal dementia].

PMID- 7623940
TI  - [The role of andrology in the diagnosis and treatment of fertility disorders].

PMID- 7623941
TI  - Coming soon to a clinic near you.

PMID- 7623942
TI  - Further thoughts and observations regarding dementia evaluation.

PMID- 7623943
TI  - Healthcare and antitrust.

PMID- 7623944
TI  - Recurrent spontaneous abortion.
AB  - The patient with recurrent pregnancy loss is often frustrated and on the verge of
      despair. Evaluation can sometimes take several visits, allowing the physician the
      time and opportunity to provide emotional support to the couple. With proper
      evaluation and therapy, the majority of patients will become pregnant. For those
      who have exhausted diagnostic and treatment options, the physician should
      encourage consideration of assisted reproductive technologies or adoption.

PMID- 7623945
TI  - Intraarticular fracture of the calcaneus.
AB  - The treatment of displaced intraarticular fractures of the calcaneus continues to
      challenge the orthopaedic community. The recent development of prognostic
      classification systems based on computerized tomography has clarified the roles
      of non-operative and operative treatment. It has also opened the door for further
      prospective study of the appropriate treatment of this injury and comparison of
      operative methods. Based on current literature and our experience, we recommend
      CT evaluation of all intraarticular fractures of the os calcis in patients who
      are operative candidates with treatment guided by fracture classification.

PMID- 7623946
TI  - Patent ductus arteriosus.

PMID- 7623947
TI  - Functional magnetic resonance imaging of the human motor cortex.
AB  - Functional magnetic resonance (MR) imaging of the brain was performed during
      motor task activation in five normal subjects and a patient with meningioma using
      conventional fast low-angle shot sequences and a 2.0 T system. A high intensity
      area in the motor cortex was observed in all normal subjects. Single-slice
      studies showed the right-sided finger task produced an increase of 1.9-23.5%
      (6.67 +/- 4.36%) in the signal intensity of the left motor cortex, while the left
      sided finger task increased the signal by 1.5-18.2% (6.09 +/- 3.34%) in the right
      motor cortex. There was no significant difference between the sides. Multiple
      slice studies also showed the activated motor cortex as a high intensity area.
      The maximum signal intensity increase in the activated motor area was 11.0% for
      the left motor cortex and 8.8% for the right motor cortex. There was no
      significant difference between the sides. Preoperative mapping of the patient
      with meningioma showed that the motor cortex was displaced posteriorly by the
      tumor. Functional MR imaging is possible with a standard MR imaging system and
      conventional gradient echo sequences. Useful clinical information can be obtained
      by preoperative mapping of the motor cortex.

PMID- 7623948
TI  - Effect of spinal cord stretching due to head flexion on intramedullary pressure.
AB  - The effect of the longitudinal stretching force of the spinal cord on
      intramedullary pressure was investigated using our method for measuring
      intramedullary pressure of the spinal cord with implanted balloons. The
      transverse compressive force against the posterior wall of the spinal column was
      excluded by measuring the intramedullary pressure during flexion of the head with
      the middle and lower cervical spine in the neutral position. The intramedullary
      pressure of the cervical spinal cord was measured simultaneously at the C-2, C-4,
      and C-6 levels in 10 mongrel dogs, in three head positions: neutral, and head
      extension and flexion. Head flexion caused significant increases in the
      intramedullary pressure at C-2, C-4, and C-6. The pressure increase in the middle
      to lower cervical cord must have been due to the transmission of the longitudinal
      stretching force of the cord itself, and may be a factor in the development of
      intramedullary disorders such as syringomyelia and intramedullary neoplasms.

PMID- 7623949
TI  - Growth rate of intracranial meningioma: tumor doubling time and proliferating
      cell nuclear antigen staining index.
AB  - The relationship between tumor doubling time, estimated by serial computed
      tomography (CT), and the proliferating cell nuclear antigen (PCNA) staining index
      of the tumor specimen was analyzed in 12 patients with nine partially or
      subtotally resected meningiomas and three meningiomas which recurred after gross
      total removal. There were nine meningothelial and three fibrous meningiomas.
      Malignant meningiomas and hemangiopericytomas were excluded. Serial CT was
      performed at various intervals ranging from 354 to 2007 days. Formalin-fixed,
      paraffin-embedded archival tissues were immunohistochemically stained using the
      avidin-biotin complex method with monoclonal antibody against PCNA. Percentages
      of PCNA-positive cells were calculated in 10 microscopic fields to determine the
      mean PCNA staining index. PCNA staining indexes varied from 0.13% to 7.46%. The
      tumor doubling time ranged from 197 to 7943 days and demonstrated a significant
      inverse rank correlation with the PCNA staining index (r = -0.89, p = 0.003).
      Meningiomas with PCNA staining indexes higher than 1% have comparatively short
      tumor doubling times of less than 5 years. PCNA immunostaining is a useful method
      for evaluating the proliferative activity of meningiomas.

PMID- 7623950
TI  - Changes in the level of 7 alpha-hydroxy-3-oxo-4-cholestenoic acid in
      cerebrospinal fluid after subarachnoid hemorrhage.
AB  - A high concentration of a type of cholic acid, 7 alpha-hydroxy-3-oxo-4
      cholestenoic acid, is observed in the content of chronic subdural hematoma. To
      investigate the possible causes, the level of this compound was measured in the
      cerebrospinal fluid of patients who underwent surgery for aneurysmal subarachnoid
      hemorrhage or non-hemorrhagic diseases. The maximum level was significantly
      higher in the aneurysmal subarachnoid hemorrhage patients, indicating that
      surgical intervention did not cause the postoperative increase in the level of
      this compound in the cerebrospinal fluid. Monitoring of plasma levels showed no
      postoperative increase. In vitro culture of a mixture of arterial blood and
      cerebrospinal fluid failed to show the de novo production of this compound. These
      results strongly suggest extrahepatic intracranial production of this cholic acid
      occurs in subarachnoid hemorrhage. The high concentration of this compound in
      both chronic subdural hematoma and subarachnoid hemorrhage suggests a possible
      role for 7 alpha-hydroxy-3-oxo-4-cholestenoic acid in intracranial hemorrhagic
      disorders.

PMID- 7623951
TI  - Observation of vasospasm after subarachnoid hemorrhage by magnetic resonance
      angiography--a preliminary study.
AB  - Serial evaluation of cerebral vasospasm following subarachnoid hemorrhage was
      attempted in 11 patients using magnetic resonance (MR) angiography. MR
      angiography demonstrated vasospasm with angiographic confirmation in three
      patients as a segmental narrowing or loss of flow signal, usually accompanied by
      decreased distal flow signal. MR angiography also showed decreased flow signal
      suggestive of vasospasm in another patient with clinical evidence of vasospasm
      but no angiographic confirmation was possible because of poor condition. MR
      angiography showed no vasospasm in five patients without clinical evidence of
      vasospasm, except in one patient with disappearance of the unilateral anterior
      cerebral artery signal, shown to be involvement of the clipped artery. MR
      angiography is a potential method for detection of vasospasm with further
      improvement of the technique.

PMID- 7623952
TI  - Pulmonary embolism after cerebral angiography--three case reports.
AB  - Three patients developed acute pulmonary embolism after cerebral angiography. The
      diagnoses were based on the clinical symptoms and echocardiography, chest
      roentgenography, blood gas analysis, and pulmonary perfusion scans after
      intravenous injection of 5 mCi of technetium-99m-labeled human albumin
      macroaggregates. Two of the three patients achieved clinical improvement, but one
      patient with severe embolization and circulatory deterioration died in spite of
      anticoagulation therapy. Recognition of the potential risk of pulmonary embolism
      after angiography and active prophylaxis are most important in preventing this
      complication.

PMID- 7623953
TI  - Trigeminal neuralgia associated with venous angioma--case report.
AB  - A 35-year-old male presented with trigeminal neuralgia associated with venous
      angioma at the root entry zone. Magnetic resonance imaging and angiography
      demonstrated a venous angioma with a dilated petrosal draining vein, and
      displacement of the anterior inferior cerebellar artery (AICA). The AICA and
      dilated petrosal vein were both decompressed, resulting in complete relief from
      symptoms of trigeminal neuralgia for 30 months. Microvascular decompression
      rather than resection of venous angioma is recommended for treatment of such
      cases. The possibility of a venous anomaly should be considered in younger
      patients with trigeminal neuralgia.

PMID- 7623954
TI  - Early endovascular treatment for ruptured basilar bifurcation aneurysm--case
      report.
AB  - A 69-year-old male presented with sudden onset of headache. Computed tomography
      of the head demonstrated diffuse subarachnoid hemorrhage. Angiography showed a
      saccular basilar bifurcation aneurysm. Endovascular coil occlusion of the
      aneurysm on the same day enabled complete obliteration of the aneurysm. He did
      not develop vasospasm and returned home 4 months later. Early endovascular
      occlusion of the aneurysmal sac is an alternative method for the management of
      ruptured basilar bifurcation aneurysms.

PMID- 7623955
TI  - Variation in appearance of glioma on serial thallium-201 single photon emission
      computed tomography--case report.
AB  - A 63-year-old female presented with recurrent glioblastoma at the site of a right
      parietal glioblastoma which was diagnosed 1 year before. She was treated at that
      time by total removal of the tumor, irradiation, and chemotherapy. Four months
      after the initial treatment, serial thallium-201 single photon emission computed
      tomography (201Tl SPECT) showed increased uptake at the edge of the original
      tumor site. The index, the ratio of 201Tl uptake in the lesion to the normal
      brain, was 2.9 which suggested a recurrent tumor. Magnetic resonance images with
      gadolinium over the next 7 months demonstrated an enhanced mass lesion at the
      site of primary tumor resection and a new enhanced mass in the right temporal
      lobe. The lesion in the right parietal lobe had a 201Tl uptake index of 2.5,
      while the lesion in the right temporal lobe had an index of 1.5. Re-craniotomy
      and total resection of the tumors in the right parietal and temporal lobes were
      performed. The histological diagnosis of both tumors was glioblastoma. The
      proposed use of 201Tl SPECT for the differential diagnosis of recurrent glioma
      and radiation necrosis should be carefully considered because the 201Tl uptake
      index can vary in tumor with the same malignancy grade.

PMID- 7623956
TI  - Occult intrasacral meningocele with tethered cord--case report.
AB  - A 32-year-old female presented with a history of intermittent, severe lower back
      pain, exacerbated by pregnancy and persisting for several years. Magnetic
      resonance (MR) imaging showed a sacral mass as a low signal intensity area on the
      T1-weighted image and a high signal intensity area on the T2-weighted image,
      consistent with a cystic structure containing cerebrospinal fluid. A tethered
      cord attached to the thecal sac was also confirmed. Sacral laminectomy revealed
      thinned sacral vertebral laminae, but no neuronal elements existed within the
      cyst. The cyst was attached to the distal thecal sac by a small fistula. The
      thecal sac was explored, revealing a thick filum terminale, which was transected.
      The severe pain resolved postoperatively. This type of meningeal cyst, often
      called "occult intrasacral meningocele," is best diagnosed by MR imaging. Surgery
      to obliterate the fistulous tract is the optimum treatment. Total removal of the
      cyst is unnecessary, but evaluation of other associated congenial abnormalities
      is important.

PMID- 7623957
TI  - The metabotropic glutamate receptors: structure and functions.
AB  - Glutamate is the main excitatory neurotransmitter in the brain. For many years it
      has been considered to act only on ligand-gated receptor channels--termed NMDA,
      AMPA and kainate receptors--involved in the fast excitatory synaptic
      transmission. Recently, glutamate has been shown to regulate ion channels and
      enzymes producing second messengers via specific receptors coupled to G-proteins.
      The existence of these receptors, called metabotropic glutamate receptors, is
      changing our views on the functioning of fast excitatory synapses.

PMID- 7623958
TI  - Rapid and long lasting reduction of the hypothermic effect of a D2 dopamine
      agonist after an intracerebroventricular injection of 6-hydroxydopamine.
AB  - In mice pretreated intracerebroventricularly (i.c.v.) with 6-hydroxydopamine
      (6OHDA) (50 micrograms per mouse), as soon as the hypothermia elicited by the
      neurotoxin had vanished (3 hr), the hypothermic effect induced by the direct D2
      dopamine receptor agonist RU 24926 (1 mg/kg, s.c.), was almost completely
      suppressed. This reduction in hypothermic effect was observed more than 1 month
      after the 6OHDA injection. On the 3rd day after 6OHDA injection, this reduction
      was observed for all tested doses of RU 24926 (0.25-2 mg/kg). It was prevented
      when an i.p. administration of the norepinephrine uptake inhibitor desipramine
      (20 mg/kg) was performed 30 min before the 6OHDA i.c.v. injection. It was not
      modified when an i.p. administration of the dopamine uptake inhibitor GBR 12783
      (20 mg/kg) was performed 30 min before the 6OHDA i.c.v. injection. The 6OHDA
      i.c.v. injection modified significantly neither the dopamine nor the serotonin
      hypothalamic contents. On the contrary it resulted in a marked decrease (-73%) of
      the norepinephrine hypothalamic content, which was unchanged by the
      administration of GBR 12783 (20 mg/kg, i.p.) 30 min before 6OHDA, but completely
      prevented by desipramine (20 mg/kg, i.p.) 30 min before 6OHDA i.c.v. injection.
      It is concluded that the hypothermic effect resulting from the stimulation of D2
      dopamine receptors involves a central norepinephrine transmission, which is very
      rapidly altered after 6OHDA administration.

PMID- 7623959
TI  - Pharmacological evidence for the involvement of sigma sites in DTG-induced
      contralateral circling in rats.
AB  - The central distribution of sigma sites labelled by di-o-tolylguanidine (DTG), a
      compound which has specific affinity for sigma sites, and its ability to produce
      postural movements, are consistent with the hypothesis that sigma sites may play
      a functional role in the regulation of movement. The aim of the present study was
      to evaluate the specificity of the circling behaviour induced by unilateral
      intranigral injection of DTG in rats. As previously described, DTG produced dose
      dependent unilateral rotations (2.5-20 nmol/rat). A similar dose-dependent
      circling behaviour was observed with DMTG and (+) NANM (3-40 nmol/rat), compounds
      which bind to both sigma and PCP sites, and with haloperidol (3-20 nmol/rat)
      whereas raclopride and D,L-sulpiride did not elicit any circling (10 nmol/rat).
      DTG-induced circling after intranigral injection (10 nmol/rat) was decreased in a
      dose-dependent manner by rimcazole (20-40 mg/kg, i.p.), a selective ligand for
      sigma sites, and by BMY 14802 (3, 10, 30 mg/kg, i.p.), ifenprodil and eliprodil
      (1, 3, 10 mg/kg, i.p.), non-selective sigma ligands. In contrast, naloxone (1
      mg/kg, s.c.) and CGS 19755 (1, 3, 10 mg/kg, i.p.) did not change the DTG-induced
      circling. Eliprodil failed to inhibit circling produced by compounds devoid of
      any affinity for sigma sites such as APV, dizocilpine or muscimol, indicating the
      specificity of the inhibition observed with eliprodil on the DTG-induced
      circling.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7623960
TI  - Inhibition of the morphine withdrawal syndrome and the development of physical
      dependence by lithium in mice.
AB  - Due to the claim that lithium (Li+) reduces morphine self-administration in
      dependent rats, the effects of acute and chronic Li+ treatments on naloxone
      precipitated withdrawal syndrome and physical dependence development to morphine
      in mice chronically treated with morphine, were evaluated. Morphine dependency
      was induced by the ingestion of morphine through drinking water in increasing
      doses for 10 days. Physical dependence to morphine was observed by precipitating
      an abstinence syndrome with naloxone (2 mg/kg, i.p.). In the acute experiments,
      Li+ (1 and 10 mg/kg, i.p.) was administered 1 hr prior to challenge with naloxone
      to morphine-dependent mice whereas for chronic studies, mice received morphine
      concomitant with Li+ (1200 mg/l) as drinking fluid for 10 days. Results obtained
      indicate that acute Li+ administration significantly reduced the withdrawal
      signs, and we were unable to induce some degree of morphine dependency in co
      administration of Li+ to mice receiving chronic morphine treatment as compared to
      chronic morphine administration alone. The present study revealed that even in
      mice with very much lower serum Li+ levels than the commonly accepted therapeutic
      range there was a significant reduction in the withdrawal signs. It has been
      shown that Li+ and morphine have diverse effects on the transmembrane signal
      control systems. The interaction of Li+ and morphine might be through these
      systems.

PMID- 7623961
TI  - Actions of phenylglycine derivatives at L-AP4 receptors in retinal ON bipolar
      cells.
AB  - Phenylglycine derivatives can act as agonists or antagonists at different
      metabotropic glutamate receptor (mGluR) subtypes, including subtypes sensitive to
      L-2-amino-4-phosphonobutyric acid (L-AP4). We examined the pharmacology of four
      phenylglycines at L-AP4 receptors in ON bipolar cells of the amphibian retina in
      situ. As previously shown for S-4-carboxy-3-hydroxyphenylglycine (S-4C3H-PG)
      (Thoreson W. B. and Miller R. F., J. Gen. Physiol. 103, 1019-1034, 1994), whole
      cell recordings indicate that S-3-carboxy-4-hydroxyphenylglycine (S-3C4H-PG) and
      S-4-carboxyphenylglycine (S-4C-PG) are L-AP4 receptor agonists in retina.
      Concentration-response curves for these compounds were obtained using the b-wave
      of the electroretinogram (ERG) as an assay for ON bipolar cell activity. The rank
      order potency and IC50 values obtained were: S-4C-PG (204 microM) > S-4C3H-PG
      (399 microM) > or = S-3C4H-PG (558 microM). At 1 mM, RS-alpha-methyl-4
      carboxyphenylglycine (RS-M4C-PG) suppressed the b-wave by less than 20%. This
      weak effect is attributed to agonist actions of RS-M4C-PG. The agonist actions of
      phenylglycines in retina are different from their effects at L-AP4 receptors in
      spinal cord or the expressed L-AP4-sensitive receptor subtype, mGluR4 (Kemp et
      al., Eur. J. Pharmac. Molec. Pharmac., 266, 187-192, 1994; Thomsen et al., Eur.
      J. Pharmac. Molec. Pharmac., 267, 77-84, 1994; Hayashi et al., J. Neurosci., 14,
      3370-3377, 1994).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7623962
TI  - Pharmacological heterogeneity of NMDA receptors in cerebellar granule cells in
      immature rat slices. A microfluorimetric study with the [Ca2+]i sensitive dye
      Indo-1.
AB  - We have developed a technique for monitoring the internal calcium concentration-
      [Ca2+]i--in a single selected cell in cerebellar slices of 8-day-old rats. In
      post-migratory granule cells NMDA induced a rapid, reversible and concentration
      dependent increase in [Ca2+]i (+22% at 10 microM and +210% at 100 microM). This
      effect was dependent on the presence of Ca2+ in the extracellular medium. When
      Mg2+ was absent from the perfusion buffer the sensitivity to NMDA was greatly
      increased (+108% at 10 microM). The NMDA response was not affected by glycine
      site agonists or by tetrodotoxin, a sodium channel blocker. In the absence of
      magnesium, the NMDA (10 microM)-induced increase in [Ca2+]i was prevented in a
      monophasic manner by the recognition site antagonist 2-amino-phosphonovalerate (2
      APV; IC50 = 13 microM), and in a biphasic manner by the glycine site antagonist 7
      chlorokynurenate (IC50s = 25 nM and 5.9 microM) and by the channel blocker
      dizocilpine (IC50s = 5 nM and 3 microM). In contrast, this NMDA response was only
      partially antagonized by the polyamine site antagonists ifenprodil and eliprodil
      (maximal inhibition approximately 50% at concentrations > or = 10 microM, IC50 1
      and 2 microM, respectively). These results demonstrate the presence in granule
      cells from immature rat cerebellum of at least two NMDA receptor populations
      which can be differentiated by their sensitivity to inhibitors acting upon the
      different sites of the NMDA receptor complex.

PMID- 7623963
TI  - Thalamic NMDA receptors in the gamma-hydroxybutyrate model of absence seizures: a
      cerebral microinjection study in rats.
AB  - The possible role of thalamic NMDA receptors in the generation of experimental
      absence-like seizures was studied in rats. Bilaterally synchronous spike wave
      discharges were induced by gamma-hydroxybutyric acid (GHB) and were recorded
      simultaneously from different thalamic nuclei and the layers I-IV of
      frontoparietal cortex. Bilateral infusions of NMDA into thalamic mediodorsal
      nucleus, the intralaminar central lateral/paracentral nucleus,
      ventroposterolateral, or reticular nucleus of the thalamus in conscious rats,
      prior to GHB administration suppressed GHB-induced SWD in a dose dependent
      manner. However, no such suppression of GHB-induced SWD was observed when NMDA
      infusions were made into the above thalamic sites after the onset or development
      of GHB-induced SWD. Pretreatment with high doses of competitive (CGP 43487) or
      non-competitive NMDA receptor antagonists (MK-801 and ketamine) also dose
      dependently suppressed GHB-induced SWD. Both MK-801 and CGP 43487 dose
      dependently antagonized NMDA-mediated inhibition of GHB-induced SWD activity but
      at lower doses did not produce significant inhibition of GHB-induced SWD. The
      anti-SWD effects of NMDA, MK-801 and ketamine but not CGP 43487 were more
      pronounced in the mediodorsal and intralaminar thalamic nuclei than in the
      ventroposterolateral or reticular nucleus of thalamus. Because low doses of NMDA
      antagonists failed to disrupt the generation of seizures in the GHB model, these
      findings do not support a role for thalamic NMDA receptors in the pathogenesis of
      absence-like seizures induced by gamma-hydroxybutyric acid.

PMID- 7623964
TI  - Discriminative stimulus effects of excitatory amino acid agonists in rats.
AB  - Sixteen male Sprague-Dawley rats were trained to discriminate 30 mg/kg i.p. NMDA
      from saline using a 2-lever operant procedure. Responding was maintained under a
      FR 32 schedule of food reinforcement. Substitution tests were completed with NMDA
      (3-56 mg/kg) and other putative excitatory amino acids, L-glutamate (30-560
      mg/kg), L-aspartate (30-300 mg/kg), L-homocysteic acid (100-1500 mg/kg), L
      cysteine (30-1000 mg/kg), monosodium glutamate (100-3000 mg/kg), kainic acid (0.1
      3 mg/kg) and the selective NMDA receptor agonist, D,L-(tetrazol-5-yl)glycine (LY
      285265) (0.01-1.0 mg/kg). LY 285265 fully substituted for NMDA and was approx 100
      fold more potent than NMDA for producing NMDA-like discriminative stimulus
      effects. Partial substitution occurred with monosodium glutamate, L-glutamate and
      L-homocysteic acid, resulting in mean maximum levels of 49-59% NMDA-lever
      responding, however response rate decreases were only obtained with 3000 mg/kg
      monosodium glutamate, suggesting that behaviorally active doses of the other
      compounds may not have been fully studied. L-Cysteine, kainic acid and L
      aspartate failed to substitute for NMDA or produce decreases in response rates.
      Unlike with other excitatory agonists tested, full substitution occurred only
      with LY 285265, providing evidence that selective NMDA receptor activation is the
      basis for the NMDA discriminative stimulus. These results also suggest that LY
      285265 is a potent, systemically active, selective agonist for the NMDA receptor.

PMID- 7623965
TI  - Nitric oxide may be a mediator of effects of prolonged but not brief anoxia in
      CA1 neurons in slices.
AB  - As a known vasodilator, nitric oxide (NO) probably acts by hyperpolarizing smooth
      muscle by increasing K conductance (GK). Therefore NO could mediate the anoxic
      hyperpolarizations of brain neurons that are also mediated by GK. We investigated
      this question by recording from CA1 neurons in submerged hippocampal slices (from
      rats), kept at 33 degrees C. Incubation with the NO synthase inhibitor N omega
      nitro-L-arginine methyl ester (L-NAME; 200 microM) had no significant effect on
      CA1 population spikes (delta = 2.5%, SEM +/- 3.1%, n = 7) or on the time course
      of their suppression by brief exposure to anoxia (2-3 min). In intracellular
      recordings, L-NAME did not change the resting membrane potential or input
      resistance (n = 10). In the presence of L-NAME, anoxic changes were not
      significantly different: the cells were hyperpolarized by 6.4 +/- 0.74 mV (6.3 +/
      0.82 mV for controls) and their resistance decreased by 16 +/- 3.2% (18 +/- 1.4%
      for controls, n = 10). In whole-cell recordings from another 15 cells (clamped at
      approximately -50 mV, near resting level), L-NAME also had no consistent effect
      on input conductase (GN) or holding current (IH); and the anoxic increased in GN
      were unchanged (44 +/- 12% before and 48 +/- 20% after, for n = 10). Thus NO does
      not appear to be a significant element in the mechanism of membrane and synaptic
      changes during brief anoxia in CA1 neurons in slices.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7623966
TI  - Bradykinin modulation of alpha 2-adrenoceptors in the nucleus tractus solitarii
      of the rat. An in vitro autoradiographical study.
AB  - The existence of an interaction between bradykinin (Bk) receptors and the alpha 2
      adrenoceptors were evaluated by means of quantitative receptor autoradiography in
      the nucleus tractus solitarii (NTS) of the rat. In competition experiments using
      L-noradrenaline (0.1 nM to 10 microM) against [3H]p-aminoclonidine ([3H]PAC) (10
      nM) it was observed that Bk produced an increase in the IC50 value of L
      noradrenaline in a concentration response manner, which reached a maximum of
      about 100% with 10 nM of the peptide associated with a small decrease in the B0
      value (15%). In saturation experiments Bk promoted a significant increase in the
      KD value of [3H]PAC (60%) and a decrease in the Bmax value (36%). The specific Bk
      B2 receptor antagonist HOE-140 fully counteracted the effect of Bk on the alpha 2
      adrenoceptors as analyzed by the competition experiments. Furthermore, des-Arg9
      Bk, a Bk analog which exhibits selective agonist activity to the Bk B1 receptor
      subtype did not produce any effect on the alpha 2-adrenoceptors, suggesting that
      the Bk B2 receptor subtype may be mediating the Bk action on the alpha 2
      adrenoceptors in the NTS. The effect of Bk (10 nM) was analyzed together with GTP
      (0.1 nM) in competition experiments and no change in the ability of L
      noradrenaline to compete for [3H]PAC binding sites was observed in the presence
      of GTP, suggesting that the receptor interaction between the Bk B2 receptors and
      the alpha 2-adrenoceptors may be a G-protein dependent mechanism.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7623967
TI  - Differential inhibition of serotonin release by 5-HT and NA reuptake blockers
      after systemic administration.
AB  - The inhibition of serotonin (5-HT) release produced by antidepressants varying in
      relative selectivity for blocking uptake of 5-HT and noradrenaline (NA) was
      compared. Release was measured by microdialysis in anesthetized rats with nerve
      terminal 5-HT uptake inhibited by local infusion of citalopram (1 microM) through
      a dialysis probe in hippocampus. With 5-HT uptake first blocked in hippocampus,
      systemic injection of uptake inhibitors produced decreases in dialysate 5-HT,
      presumably due to autoreceptor stimulation in the raphe. The largest decreases
      (about 60-70%) in 5-HT were produced by the selective 5-HT uptake inhibitors
      sertraline, paroxetine and citalopram. Nonselective blockers caused less
      suppression of release. Thus, the maximum decrease in 5-HT was 35% after
      clomipramine, a less selective 5-HT uptake inhibitor, and < or = 30% after the
      nonselective 5-HT/NA uptake blockers imipramine and amitriptyline, 5-HT was not
      decreased after maprotiline, a selective NA uptake blocker. Pretreatment with
      (+)WAY100135 to block 5-HT1A autoreceptors, abolished the inhibition of 5-HT
      release produced by systemic sertraline, clomipramine and imipramine. One
      explanation for the difference between selective and nonselective inhibitors with
      respect to central 5-HT release, is the excitatory effect of (alpha 1) adrenergic
      receptor stimulation on 5-HT neuronal discharge. However, pretreatment with alpha
      methyl-p-tyrosine to deplete NA, did not influence the inhibition of 5-HT release
      produced by imipramine.

PMID- 7623969
TI  - [Medical emergencies in acute pancreatitis].

PMID- 7623968
TI  - Effects of 5-HT3 receptor antagonists on neuroleptic-induced catalepsy in mice.
AB  - Typical neuroleptics (e.g. haloperidol) can induce a cataleptic state in rodents
      by means of striatal DA receptor blockade. It has been shown that drugs which
      influence central serotonergic (5-HTergic) mechanisms can modify neuroleptic
      induced catalepsy, suggesting that dopaminergic transmission is under 5-HTergic
      modulation. The aim of this study was to examine the effects of bemesetron and
      granisetron, two selective 5-HT3 receptor antagonists, on this catalepsy in mice.
      Catalepsy was induced with haloperidol (1.5 mg/kg, i.p.) and measured at 30-min
      intervals by means of a bar test. Drugs (or saline, for the controls) were
      injected i.p. 20 min before haloperidol, with each animal used only once.
      Bemesetron significantly reduced catalepsy at a dose of 1 mg/kg, whilst 10 mg/kg
      potentiated the phenomenon and 0.1 mg/kg was found to be without effect.
      Granisetron inhibited catalepsy at doses of 0.04 and 0.1 mg/kg while 4 mg/kg of
      the antagonist significantly increased the duration of catalepsy. These data
      suggest that 5-HT3 receptors play a role in neuroleptic-induced catalepsy.
      Considering the high affinities of both antagonists for 5-HT3 receptors, it is
      tempting to speculate that the potentiation of catalepsy by high doses of them is
      due to non 5-HT3 receptor mechanisms.

PMID- 7623970
TI  - [Estrogens and cartilage: an ex vivo ultrastructural study].
AB  - The ultrastructural change brought about by administration of oestrogens on
      articular cartilage were evaluated in the course of the present study. To this
      end 3 stabilized postmenopausal patients were selected who were to undergo
      bilateral hip prosthesis. After the first operation the patients were started on
      continuous estriol treatment by oral route for 6 months. For study purposes a
      cartilage fragment was obtained during the first (baseline time) operation and
      the second operation (final time, after 6 months of oestrogen therapy). The
      results of histologic examination of the semifine sections as well as the
      submicroscopic patterns of the various cell elements showed great similarity in
      all cases considered. Ultrastructure examination had evidenced signs of marked
      cell damage in the 3 initial samples. After treatment with oestrogens,
      chondrocyte metabolic activity was resumed, evidenced by the presence of
      extensive granular endoplasmic reticulum with hypertrophic cisternae, finely
      dispersed nuclear chromatin and more regular nuclear membrane. These findings
      would appear to support metabolic stimulation of articular cartilage by the
      oestrogens.

PMID- 7623971
TI  - [The computerized outpatient management of subjects at neoplastic risk].
AB  - The authors reviewed literature data regarding risk factors of cancer in order to
      produce a software that could identify asymptomatic subjects at "neoplastic risk"
      by means of the analysis of the relative risk (RR) of each factor of his/her life
      style. More in detail, the relationship between diet and cancer, tobacco use,
      alcohol consumption, sexual behaviour, parity and other obstetric-gynecologic
      aspects, medications, occupational hazards, environmental pollution and genetic
      susceptibility were reviewed. A complex multi-parametric evaluation system was
      realized to calculate risk of cancers through computerized elaboration. The
      program operates on anamnestic, objective and instrumental data derived from a
      clinical data-base.

PMID- 7623973
TI  - [Antibiotic prophylaxis with mezlocillin in elective biliary surgery].
AB  - The authors report their experience of antibiotic prophylaxis in elective biliary
      surgery pertinent to 246 operated patients treated with short-term prophylaxis
      with mezlocillin. This method has turned out to be efficacious in reducing
      postoperative infections incidence, particularly in simple cholecystectomy.
      Therefore the authors advise using such a procedure in this frequent operation
      too.

PMID- 7623972
TI  - [Leukocytic procoagulant activity and chemotherapeutic drugs: the comparative
      effects of cisplatin and carboplatin on lympho-/monocytic procoagulant activity
      in vitro].
AB  - It is well known that a number of chemotherapeutic agents are able to induce
      procoagulating activity not only in neoplastic cells but also in normal,
      monocyte/macrophage cells, and some of them, including cisplatin, even increase
      procoagulating activity of the factor already expressed, providing a further
      example of the possible co-participation of chemotherapy in the onset of
      thrombotic complications in cancer patients. Carboplatin is an analogue of
      cisplatin but differs strikingly in terms of its collateral effects, in
      particular being less oto- and nephrotoxic. To the authors' knowledge there are
      no data regarding the possible effect of carboplatin on lympho/monocyte
      procoagulating activity. This study shows that not only platin but also
      carboplatin is able to increment the levels of lympho/monocyte procoagulating
      activity in vitro, with a dose-dependent effect, and to synergize with bacterial
      endotoxin in increasing this leukocyte activity, although the synergic effect is
      significantly greater in the case of carboplatin. The importance of these
      findings at a practical and clinical and clinical level still remains to be
      defined, in particular in the light of the different pharmacokinetic behaviour of
      these two chemotherapeutic agents and in the context of those neoplastic diseases
      for which cisplatin and carboplatin treatment is most frequently used.

PMID- 7623974
TI  - [The analgesic effect of galactosaminoglycuronoglycan in the treatment of
      osteoarthrosis].
AB  - The analgesic effect of galactosamineglucuronoglycan sulfate (GGG) was evaluated
      in a series of patients with moderate to severe coxarthrosis and gonarthrosis.
      GGG was used at the daily dose of 800 mg, in conjunction with indomethacin, for a
      period of 6 months. In compliance with this controlled study the results obtained
      were compared with those observed in another group of patients with similar
      pathologies who were treated with indomethacin alone. Statistical elaboration of
      the values "between times" and "between treatments" showed that the combined
      treatment led to significantly better results; tolerance was good and compliance
      by the patients satisfactory.

PMID- 7623975
TI  - [1000 osteoarthrosis patients in treatment with GGGs: an assessment of joint
      pain].
AB  - The analgesic activity of a chondroprotective agent--galactosamineglucuronoglycan
      sulphate (Condral) was evaluated in the course of an open investigation in a
      large number of outpatients attending the Istituto Emilio Bruzzone of Genoa or
      related Centres. Out of 1720 outpatients seen, 1000 were treated for 2 years with
      800-1200 mg daily of GGG in one single administration (2-3 sachets or capsules of
      400 mg) By the results obtained GGG was shown to have analgesic activity in a
      large number of cases. Tolerance of the treatment was good and no significant
      clinical side effects were ever observed.

PMID- 7623977
TI  - An EDTA Registry for the year 2000?

PMID- 7623976
TI  - [The CO2 laser treatment of melanotic lesions of the oral mucosa. A clinical case
      report].
AB  - The authors, in a careful review of the literature, talk about the melanotic
      lesions of the mucous membranes of the oral cavity, explaining the
      etiopathogenesis, the various classifications, the diagnosis and the therapy.
      They also expound the features of laser and its application in management of a
      clinical case of melanotic lesion of the oral cavity.

PMID- 7623978
TI  - Presence and future of the Registry--how to keep up with advances in computer
      sciences?

PMID- 7623979
TI  - RENINE, a relational registry. Registratie Nierfunctievervanging Nederland.

PMID- 7623980
TI  - Quality assurance in renal replacement therapy (RRT)--background of a developing
      German National Registry for RRT. QuaSi-Niere Task Group.

PMID- 7623981
TI  - Regional registry of dialysis and transplantation of Piedmont, Italy (RPDT).
      Thirteen years of experience. Regional Registry of Dialysis and Transplantation.

PMID- 7623983
TI  - Parathyroid hormone and blood pressure--is there a relationship?

PMID- 7623984
TI  - Points to remember when selecting dialysate calcium concentration.

PMID- 7623982
TI  - Is parental hypertension a risk factor for the development of nephropathy in
      IDDM.

PMID- 7623985
TI  - Adynamic bone disease--is it actually a disease?

PMID- 7623986
TI  - Hyperlipidemia after renal transplantation--facts and potential implications.

PMID- 7623987
TI  - The rising tide of diabetic nephropathy--the warning before the flood?

PMID- 7623988
TI  - The rising tide of endstage renal failure from diabetic nephropathy type II--an
      epidemiological analysis.
AB  - In recent years there has been a substantial increase in the proportion of
      patients requiring renal replacement therapy who suffer from diabetes mellitus.
      In the lower Neckar region, a survey has been made comprising all patients
      admitted for renal replacement therapy from 1.1.1993-30.6.1994. Out of a total of
      225 patients admitted, 95 suffered from diabetes (10 type I, 85 type II). The
      estimated annual incidence of terminal renal failure with diabetes was
      52/mio/year. At the same time, 79 patients who suffered from diabetes were
      admitted to the renal unit in Heidelberg (outpatient clinic and ward) for
      evaluation of de novo renal failure (approximately 176/mio/year); standard
      primary chronic renal disease was found in 19/79 of these diabetic patients
      (25%). The discrepancy between the annual incidence of (i) renal failure and of
      (ii) terminal renal failure suggests that a high proportion of patients with
      diabetes (mainly type II) and renal failure, dies prior to reaching terminal
      renal failure. Potential reasons for the increasing incidence of endstage renal
      failure from diabetes type II are (i) the increasing prevalence of type II
      diabetes in Germany in recent decades, (ii) aging of the population in view of
      the known greater prevalence of type II diabetes in older individuals and (iii)
      improved survival of patients with type II diabetes secondary to diminished
      cardiovascular mortality. Particularly because of the latter factor a further
      increase of endstage renal failure in patients with type II diabetes must be
      anticipated.

PMID- 7623989
TI  - High prevalence of and risk factors for hepatitis C in haemodialysis patients in
      Saudi Arabia: a need for new dialysis strategies.
AB  - Non-A, non-B is a major form of hepatitis in haemodialysis (HD) patients.
      Hepatitis C virus (HCV) has been recently identified as the leading cause of non
      A, non-B hepatitis in HD. A variable prevalence of hepatitis in HD has appeared
      in the literature, ranging between 1% and 29% in the Western world, and between
      30% and 54% in Saudi Arabia, but all these reports used first-generation ELISA.
      Using second-generation enzyme immunoassay, we conducted a multi-centre study
      involving 22 HD centres all over Saudi Arabia in order to establish the
      prevalence and risk factors for HCV in HD patients in Saudi Arabia. A total of
      1147 patients were studied, with a mean age of 43.4 +/- 15.3 years. Five hundred
      and eighty were males and 567 were females. The overall prevalence rate of
      positive anti-HCV was 68%, with a range from as low as 14.5%, to 94.7%. To our
      knowledge, this is the highest value reported among dialysis patients world-wide.
      A positive correlation was found between anti-HCV positivity and male sex (P =
      0.005), longer duration on dialysis (P = 0.002) and blood transfusion (P =
      0.003). However, interestingly 62.6% of the patients who had not had blood
      transfusion had anti-HCV antibodies. HCV antibodies were also found more
      frequently in Egyptians, Pakistanis and Yemenis than in Saudis. A comparison
      between those centres with low prevalence of positive HCV and those with high
      prevalence regarding risk factors was carried out, and it was found that the
      major difference between them was the adherence of the staff to universal
      infection precautions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7623990
TI  - Glomerulopathy induced by a single monoclonal autoantibody against GP330.
AB  - Monoclonal autoantibodies were obtained from Lewis rats with active Heymann
      nephritis. Two cloned rat/mouse hybridomas, 3D9B and 5B8C, that secreted rat
      IgG2a autoantibodies were selected for their ability to react with gp330 in ELISA
      and propagated further. Their specificity was confirmed by immunoprecipitation of
      crude antigens from a yolk sac carcinoma cell line expressing gp330. The size of
      the precipitated molecule was identical to that immunoprecipitated by previously
      described anti-gp330 antibodies. Indirect immuno-electron microscopy showed that
      3D9B exclusively stained the intermicrovillous areas of the tubular brush border
      membrane, while 5B8C stained the full tubular microvillous membrane and the
      glomerular epithelial coated pits. Passive transfer of 3D9B did not induce Ig
      deposits or functional renal damage within 7 days. However, injection of 5B8C
      caused granular glomerular deposits within 1 h, subepithelial immune aggregates
      within 6 days and antibody deposition on the brush border within 7 days. Only
      ascites production of clone 5B8C in rats, but not in mice, caused subepithelial
      immune deposits and abnormal proteinuria. This study shows that a single
      monoclonal autoantibody to gp330 is able to induce a mild form of Heymann
      nephritis.

PMID- 7623991
TI  - Additive antiproteinuric effect of ACE inhibition and a low-protein diet in human
      renal disease.
AB  - Both ACEi and a low-protein diet (LPD) are reported to reduce urinary protein
      excretion in patients with stable non-diabetic renal disease. To test whether the
      combination of both may have an additive antiproteinuric effect, we studied the
      effects of single treatment with ACEi (10 mg enalapril o.d.), LPD (target, 50%
      reduction in protein intake), and the combination of both in 14 of such patients
      with stable proteinuria exceeding 3 g per day. Baseline measurements were
      performed while patients were on a normal protein diet (NPD). In group A (n = 7),
      first the effects of a LPD were investigated, whereafter the effects of addition
      of ACEi to LPD were studied. In group B (n = 7), first the effects of ACEi were
      investigated, whereafter the effects of addition of a LPD to ACEi were studied.
      Each treatment period lasted 2 months. LPD decreased proteinuria with 17% in
      patients without ACEi treatment (group A), and similarly with 19% in patients
      with ACEi treatment (group B). The antiproteinuric response obtained with the LPD
      in individual patients ranged from -63% to +1%. This variation is at least partly
      explained by interindividual differences in diet compliance, since the
      antiproteinuric effect of the LPD was found to correlate with the achieved
      reduction in protein intake (r = 0.58, P < 0.05). ACEi lowered proteinuria with
      32% during the NPD (group B), and similarly with 43% during the LPD (group
      A).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7623992
TI  - The pressor effect of recombinant human erythropoietin is not due to decreased
      activity of the endogenous nitric oxide system.
AB  - In a subset of dialysis patients, erythropoietin (rHuEpo) treatment exacerbates
      hypertension. The mechanism of this pressor effect is unknown; however, it has
      been suggested that decreased endogenous nitric oxide (NO) activity may play a
      role. To explore this hypothesis, Sprague-Dawley rats were given rHuEpo (150 U/kg
      s.c. three times per week) or corresponding vehicle. Blood pressure, haematocrit,
      and urinary excretion of the stable NO metabolites, nitrite (NO2) and nitrate
      (NO3), were determined at baseline and 3 weeks. After 3 weeks of rHuEpo treatment
      there was a significant increase in blood pressure and haematocrit, while in
      vehicle-treated rats blood pressure and haematocrit remained at basal levels.
      Urinary excretion of NO2+NO3 increased compared to basal in rHuEpo, but not
      vehicle rats. Thus in normal rats rHuEpo does have a significant pressor effect,
      but this is not associated with decreased activity of the endogenous NO system.
      Thus decreased endogenous NO activity is not responsible for rHuEpo-associated
      hypertension. These data further suggest that endogenous NO activity is increased
      in rHuEpo-treated rats, perhaps as a counter-regulatory mechanism that limits the
      pressor effect. Whether this mechanism is active in the setting of rHuEpo-treated
      chronic renal failure in humans is unknown.

PMID- 7623993
TI  - Anaphylactoid reactions during haemodialysis in sheep are associated with
      bradykinin release.
AB  - Anaphylactoid reactions have been observed in patients treated with AN69
      dialysers and ACE inhibitors. Recently, it has been shown in vitro that AN69
      membranes induce the release of high amounts of bradykinin in plasma. To verify
      the possible role of bradykinin in these shock-like reactions, six sheep were
      dialysed in a random fashion using AN69 or the new SPAN membrane with and without
      pretreatment with captopril. All animals were dialysed for 60 min via double
      lumen Shaldon catheters. Blood samples were drawn at 0, 5, 10, 15, 30, and 60 min
      from the venous line. A total of 24 haemodialysis procedures was carried out:
      group A (n = 6), AN69 without captopril; group B (n = 6), SPAN without captopril;
      group C (n = 6), AN69 with captopril; group D (n = 6), SPAN with captopril. A
      significant bradykinin release was observed only in groups A and C, reaching peak
      values already after 5 min. Animals in group C showed the highest bradykinin
      values. In four of six animals in group C anaphylactoid reactions with severe
      hypotension were noted. From this animal model we conclude that dialysis with the
      AN69 membrane is associated with bradykinin release. Pretreatment with ACE
      inhibitors results in further increasing bradykinin levels, which lead to
      anaphylactoid reactions. In contrast, the new SPAN membrane was well tolerated
      without detectable changes in bradykinin concentrations.

PMID- 7623995
TI  - Evaluation of a preservation solution containing fructose-1,6-diphosphate and
      mannitol using the isolated perfused rat kidney. Comparison with Euro-Collins and
      University of Wisconsin solutions.
AB  - The renal preservation ability of a flushing solution (F-M) with fructose-1,6
      diphosphate (1 g/dl) and mannitol (2 g/dl) during cold ischaemia was studied with
      the isolated perfused rat kidney model and compared with the Euro-Collins (EC)
      and University of Wisconsin (UW) solutions. Kidneys were stored in hypothermia
      for 4 and 18 h after initial flushing with the solution being tested, and then
      reperfused at 37 degrees C in an isolated perfusion circuit for 90 min with a
      Krebs-Henseleit solution containing 4.5% albumin. Forty-four kidneys were studied
      and divided in a control group and six study groups according to the cold
      ischaemia time and flushing solution used. Renal functional parameters of plasma
      flow rate (PFR), renal vascular resistance (RVR), urine flow rate (UFR)
      glomerular filtration rate (GFR), fractional (FRNa) and net (TNa) sodium
      reabsortion were assessed during reperfusion. Conventional histology and
      malondialdehyde tissue levels (MDA) were also evaluated. Our results show that
      PFR, RVR, and UFR were similar in all study groups. After 4 and 18 h of cold
      ischaemia, GFR, FRNa and TNa were better, and conventional histology worse in F-M
      than in EC flushed kidneys. After 4 and 18 h of cold ischaemia, GFR, FRNa and
      TNa, in fact, were not different between F-M and UW flushed kidneys. After 4 h of
      cold ischaemia, conventional histology was similar in F-M and UW flushed kidneys.
      Nevertheless, after 18 h of cold ischaemia, UW flushed kidneys showed worse
      histological parameters than F-M flushed kidneys. After 4 h of cold ischaemia,
      MDA was similar in kidneys flushed with three solutions. After 18 h of cold
      ischaemia MDA was higher in EC than in F-M or UW flushed kidneys. In summary, our
      newly developed cold storage solution shows promising results in renal
      preservation and its ability to preserve is at least as good as UW solution
      assessed in the isolated perfused rat kidney.

PMID- 7623994
TI  - Influence of protein catabolic rate on nutritional status, morbidity and
      mortality in elderly uraemic patients on chronic haemodialysis: a prospective 3
      year follow-up study.
AB  - It has been recently reported that elderly chronic haemodialysis (CHD) patients
      have a reduced protein catabolic rate (PCRn) in spite of an adequate Kt/V.
      However until now the long-term consequences of this fact on the nutritional
      status, morbidity, and mortality were not known. This prospective study
      evaluates, over a period of 3 years, the effect of the reduced PCRn on some
      nutritional parameters, morbidity mortality in CHD patients older than 65 years
      with adequate and stable Kt/V. Over the period 1990-1993 we evaluated 42 CHD
      patients over 65 years (mean +/- SD 72 +/- 5 years). PCRn, total serum proteins,
      serum albumin concentration, body weight, body mass index (BMI) and serum
      transferrin were determined at the start of the study and followed yearly until
      the end of observation. The incidence of hospitalization/patient-year, the
      mortality rate and the causes of death were also recorded. All the patients were
      managed to maintain a Kt/V > 0.9 throughout the study. Twenty-two patients (Group
      A), mean age 70 +/- 4 years, completed the entire period of observation. Their
      Kt/V was 1.10 +/- 0.12, PCRn was 0.95 +/- 0.12 g/kg/day, and serum albumin
      concentration was 40.2 +/- 1.5 g/l, and these did not change significantly. The
      other parameters also remained stable over time. Twenty patients (Group B) died.
      Their mean age was 74 +/- 6 years. This group's Kt/V was 1.11 +/- 0.15, PCRn was
      0.94 +/- 0.18 g/kg/day, and serum albumin concentration was 39 +/- 3.1 g/l, and
      there were no significant variations between the start and the end of observation
      for all the parameters studied.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7623996
TI  - The value of different resistance parameters in distinguishing biopsy-proved
      dysfunction of renal allografts.
AB  - The data concerning the value of duplex sonography in diagnosing parenchymatous
      renal allograft dysfunction are controversial. Most early studies did not take
      into consideration the many factors influencing resistance parameters. We
      therefore performed a prospective, biopsy-controlled study with exclusion of all
      known sources of error regarding resistance parameters. Furthermore we
      investigated the value of a new resistance parameter, the systolic deceleration
      percentage. Forty-seven duplex sonographic studies were performed on 43 patients
      (30 male, 13 female, median age 47 years, range 7-70). Fourteen studies were done
      on normally functioning grafts (control group) an average of 33 days after
      transplantation. Thirty-three studies were performed on dysfunctional grafts
      immediately prior to biopsy. Grafts which had been transplanted more than a year
      previously or with vascular findings or any other clinical or sonographic
      pathology probably explaining function deterioration were excluded. In all
      patients, the resistive index (RI), pulsatility index (PI) and systolic
      deceleration percentage (DP) were calculated in the main renal artery and in the
      interlobar artery. Of the 33 grafts with dysfunction, nine had vascular rejection
      (VR), 11 interstitial rejection (IR), 11 cyclosporin A toxicity (CAT) and two
      other histologies (OR). The mean RI in normal grafts (NO) was 0.71 +/- 0.06 in
      the main artery and 0.68 +/- 0.06 in the interlobar artery, in VR 0.86 +/- 0.12
      and 0.80 +/- 0.18, in IR 0.72 +/- 0.05 and 0.70 +/- 0.07, in CAT 0.67 +/- 0.06
      and 0.65 +/- 0.07 and in OR 0.64 +/- 0.07 and 0.60 +/- 0.01.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7623997
TI  - Deep wound infections in simultaneous pancreas-kidney transplant recipients on
      peritoneal dialysis.
AB  - Peripancreatic abscess formation remains an important cause of surgical morbidity
      following simultaneous pancreas-kidney (SPK) transplants. The purpose of this
      study is to define the association, if any, between the pretransplant method of
      dialysis and the incidence of peripancreatic abscess formation. We reviewed 57
      bladder-drained SPK transplants. Of these, 42 were on haemodialysis (HD) and 15
      on peritoneal dialysis (PD) prior to transplantation. Two grafts were lost and
      three patients died as a result of peripancreatic infections for a total graft
      loss of 8.8%. The incidence of this complication was higher (P = 0.036 Pearson
      chi square) in patients on PD (40%) prior to transplant when compared to patients
      on HD (14%). The most common organism cultured from the abscesses was
      Staphylococcus epidermidis in both groups. Impairment of peritoneal macrophage
      function and accumulation of peritoneal effluent as a result of altered
      peritoneal membrane function are some of the changes that occur following chronic
      peritoneal dialysis and could explain our findings.

PMID- 7623998
TI  - Triglyceride-rich lipoprotein abnormalities in CAPD-treated patients.
AB  - In the present study intermediate-density lipoproteins (IDL) and very-low-density
      lipoproteins (VLDL) composition, structure, and mass were analysed in fasting
      uraemic patients on continuous ambulatory peritoneal dialysis (CAPD) (n = 12) and
      on haemodialysis (HD) (n = 15), and in 15 healthy volunteers. All the groups were
      matched for sex, age, and time on dialysis. Both groups of patients had elevated
      very-low-density lipoprotein levels, CAPD patients four and HD group three times
      that of control. We found a fourfold and a twofold increase in the concentration
      of IDL cholesterol in the CAPD and HD group respectively when they were compared
      with the control group. Both groups of patients present an increased VLDL mass.
      The CAPD group showed a four-fold increase in IDL mass compared with the control
      group, which indicated a preponderance of large size and suggested that defective
      IDL clearance was involved. The IDL composition of the CAPD patients was
      significantly different from that of the HD patients: a twofold increase in IDL
      mass was observed in the CAPD patients if compared with HD patients. We report
      new data concerning the metabolism of triglyceride-rich lipoproteins in CAPD
      treated patients, which confirm the adverse effect of CAPD on serum lipids.

PMID- 7623999
TI  - Hepatitis C virus--does it penetrate the haemodialysis membrane? PCR analysis of
      haemodialysis ultrafiltrate and whole blood.
AB  - Hepatitis C virus (HCV) transmission to haemodialysis patients occurs by a route
      which remains to be clarified. Most studies show a significant correlation
      between anti-HCV-seropositivity and the number of blood transfusions or the
      duration of dialysis respectively. However, even in patients who have not
      received a blood transfusion the prevalence of HCV infection was significantly
      higher than in controls. We studied 58 patients on regular haemodialysis using a
      second-generation enzyme-linked immunosorbent assay (ELISA II) followed by a
      second-generation recombinant immunosorbent assay (RIBA II) for HCV. For all
      antibody-positive or indeterminate patients, polymerase chain reaction (PCR)
      analysis was done using both whole blood and dialysed ultrafiltrate. We were able
      to show by PCR that no HCV RNA (cells or cell particles) passed through the
      dialysis membranes.

PMID- 7624000
TI  - Anticonvulsants as a cause of Fanconi syndrome.

PMID- 7624001
TI  - Lipoprotein glomerulopathy: first case in a white European.
AB  - Since 1988, 11 cases of a new entity, 'Lipoprotein glomerulopathy' (LG), were
      described in Japan. Some of these reports suggested that this glomerular lipid
      storage is due to excess apo E associated with heterozygous E2/3 apo E isoform.
      We report the first case of LG in a white European with no such lipid
      abnormalities. Proteinuria was discovered in 1967 when he was 42. Blood pressure
      and renal function were normal. Family history was negative. Renal biopsy
      disclosed lesions which were only understood at the time of the Japanese
      publications. They were composed of endocapillary glomerular deposits. Staining
      for lipids disclosed capillary loop obstruction with lipid droplets. Electron
      microscopy showed confluent droplets of various sizes obstructing capillary
      loops. Proteinuria progressively increased. In 1974 repeat renal biopsy showed
      the same lipid deposits, now associated with focal-segmental glomerulosclerosis
      (FSGS). Several serum lipoprotein and apolipoprotein studies ruled out any
      specific lipid derangement. This suggested a local glomerular disorder,
      presumably affecting the glomerular endocapillary disposal of lipids. A third
      biopsy showed progressive glomerular destruction by FSGS with persistence of the
      lipid droplets. Renal insufficiency progressed and haemodialysis was started in
      1992. This observation suggests that LG is a local glomerular, not a general
      lipid disorder and indicates that this disease is not restricted to Asian
      patients.

PMID- 7624002
TI  - Acute renal failure due to vancomycin alone.

PMID- 7624003
TI  - Control of severe hyperparathyroidism and regression of a brown tumour after
      treatment with i.v. alfacalcidol in a uraemic patient.

PMID- 7624004
TI  - Right ventricular cardiac failure and pulmonary hypertension in a long-term
      dialysis patient--unusual presentation of visceral beta 2-microglobulin
      amyloidosis.

PMID- 7624005
TI  - Corynebacterium CDC group G1 infection in a patient receiving maintenance
      haemodialysis.

PMID- 7624006
TI  - Renal oncocytoma in a long-term renal-transplant recipient.

PMID- 7624007
TI  - Don't forget visceral leishmaniasis in transplant patients.

PMID- 7624008
TI  - The hypertensive patient with subileus.

PMID- 7624009
TI  - Calcitriol and calcium carbonate therapy in early chronic renal failure.

PMID- 7624010
TI  - Endothelial cell antibodies: relevant in human disease?

PMID- 7624011
TI  - Is the dialysis membrane a safe barrier against HCV infection?

PMID- 7624012
TI  - Flucloxacillin-induced acute interstitial nephritis.

PMID- 7624013
TI  - ATP-evoked membrane current in guinea pig adrenal chromaffin cells.
AB  - Adenosine 5'-triphosphate (ATP) evoked an inward current in whole-cell voltage
      clamped adrenal chromaffin cells of the guinea pig. The reversal potential (Erev)
      of ATP-evoked current was about 0 mV in normal external solution and was shifted
      towards negative potentials by substituting Tris+ or sucrose, but not Ca2+, for
      the extracellular Na+. This current was mediated by the activation of non
      selective cation channels and had some different properties from nicotinic
      current. It is suggested that these channels may function as a part of the ATP
      induced Ca2+ influx pathway in guinea pig chromaffin cells.

PMID- 7624014
TI  - Opposite effects of angiotensin II and nitric oxide on neurons in the duck
      subfornical organ.
AB  - Angiotensin II (ANGII) is known to activate neurons in the subfornical organ
      (SFO) of mammals and birds and this activation is regarded as the basis for the
      ANGII induced increase in water intake. Application of the nitric oxide (NO)
      donor sodium nitroprusside inhibited the activity in 10 out of 12 duck SFO
      neurons, 8 of which were in addition excited by ANGII. These data, in combination
      with the histochemical detection of NO synthase in the duck SFO, demonstrate the
      involvement of NO in SFO mediated responses and might represent the cellular
      basis for the observed opposite effects of ANGII and NO on water intake.

PMID- 7624015
TI  - An avian model for the reversal of 6-hydroxydopamine induced rotating behaviour
      by neural grafting.
AB  - A new animal model of parkinsonism was established in 'Black Silkie' chickens by
      means of unilateral injections of 6-hydroxy-dopamine into the substantia nigra.
      Apomorphine produced a strong contralateral turning pattern in the lesioned
      chickens, amphetamine had no effect. 6-OHDA treated animals received embryonic
      transplants of substantia nigra cell suspensions which caused them to cease
      rotating (P < 0.01). This finding allows us to add an avian model, which offers
      unique methodological advantages, for reversal of 6-OHDA-induced rotating
      behavior by transplantation.

PMID- 7624016
TI  - Effects of menthol and cold on histamine-induced itch and skin reactions in man.
AB  - The effects of cooling and topical application of menthol on histamine-induced
      itch, wheal and flare reactions of the left lower arm were investigated in a
      threefold cross-over design with 15 healthy male volunteers. Lowering skin
      temperature by cooling from 32.8 +/- 0.3 degrees C to 29.7 +/- 0.5 degrees C
      reduced itch intensity from 260 +/- 47 units to 55 +/- 12 units (visual analogue
      scale) and flare diameters from 39.0 +/- 2.0 mm to 30.2 +/- 1.8 mm; wheal
      reactions were not affected. A similar reduction in itch was found under menthol
      (42 +/- 14 units) although skin temperature was not decreased. These findings
      suggest a central inhibitory effect of cold sensitive A-delta fibre activation on
      itch.

PMID- 7624017
TI  - Effects of local injections of botulinum toxin on electrophysiological parameters
      in patients with hemifacial spasm: role of synaptic activity and size of motor
      units.
AB  - Ten patients with typical hemifacial spasm were examined before and after
      treatment with local injections of botulinum toxin type A. After a mean follow-up
      period of 38 days there was a reduction of the compound muscle action potential
      (CMAP) of the injected orbicularis oculi muscle of 40%. Ephaptic transmission
      studied by selective stimulation of facial nerve branches revealed a preserved
      delayed response of the affected mentalis muscle. However, no delayed response
      could be recorded in the injected orbicularis oculi muscle in nine patients. The
      discrepancy between complete loss of the delayed (ephaptic) response and only
      moderate reduction of the CMAP amplitude of the direct response may be explained
      by preferential uptake of botulinum toxin type A by hyperactive synapses involved
      in ephaptic transmission.

PMID- 7624018
TI  - Ketobemidone, methadone and pethidine are non-competitive N-methyl-D-aspartate
      (NMDA) antagonists in the rat cortex and spinal cord.
AB  - The opiate agonists, ketobemidone, methadone and pethidine, were evaluated as N
      methyl-D-aspartate (NMDA) receptor antagonists using the rat cortical wedge
      preparation and the neonatal rat spinal cord preparation for electrophysiological
      studies and [3H](RS)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-im
      ine ([3H]MK-801) binding experiments using rat forebrain homogenates.
      Ketobemidone, methadone and pethidine were inhibitors of [3H]MK-801 binding with
      Ki values of 26 microM, 0.85 microM and 47 microM, respectively. In the cortex, 1
      mM ketobemidone and 1 mM methadone reduced NMDA responses, but not (RS)-2-amino-3
      (3-hydroxy-5-methylisoxazol-4-yl) propionic acid (AMPA) or kainate responses in
      an use-dependent manner, whereas 1 mM pethidine was devoid of antagonist
      activity. In the spinal cord preparation, the activities of ketobemidone and
      methadone were weaker than in cortex. In contrast, pethidine was equipotent with
      ketobemidone in the spinal cord. These results suggest that ketobemidone and
      methadone may be useful therapeutic agents in conditions where a combined opiate
      agonist and NMDA antagonist treatment is desired.

PMID- 7624019
TI  - Sensitization of cocaine-stimulated increase in extracellular levels of
      corticotropin-releasing factor from the rat amygdala after repeated
      administration as determined by intracranial microdialysis.
AB  - Using intracranial microdialysis, the effect of repeated cocaine (30 mg/kg i.p.)
      versus saline administration for 10 consecutive days upon basal and stimulated
      release of corticotropin-releasing factor (CRF) was examined in the central
      amygdaloid nucleus (CeA) of anesthetized rats. No significant differences in
      basal CRF levels between daily cocaine and saline treated groups were found.
      However, after cocaine challenge (10 mg/kg i.p.) the increase in CRF overflow was
      significantly greater in cocaine- as opposed to saline-pretreated rats (266 +/-
      55.4% versus 149 +/- 8.5% of basal levels). Local administration of 4
      aminopyridine produced a significant increase in CRF efflux (195 +/- 58.5%) in
      daily cocaine-treated rats with only a weak response in the control group (127 +/
      30.9%). These data demonstrate that repeated administration of cocaine enhances
      cocaine-induced release of CRF in the rat CeA. The sensitization of CRF release
      may play a significant role in psychostimulant-induced sensitization phenomena.

PMID- 7624021
TI  - Histochemical distribution of NADPH-diaphorase in the cerebral ganglion of the
      crayfish Cambarellus montezumae.
AB  - The presence and localization of NADPH-diaphorase in the cerebral ganglion of the
      crayfish Cambarellus montezumae was shown. The reactivity of this enzyme was
      found in the deuterocerebrum, mainly in the commissure, in fibers of olfactory
      and accessory lobes, and in the laterodorsal group of cells. The presence of this
      enzyme in these cerebral regions suggests that nitric oxide is involved in
      primary sensory afferents in the crayfish.

PMID- 7624020
TI  - Gene expression of the nicotinic acetylcholine receptor alpha 4 subunit in the
      frontal cortex in Parkinson's disease patients.
AB  - Cognitive impairment in Parkinson's disease is accompanied by a marked decrease
      of cerebrocortical nicotinic receptors. To study the putative site of impaired
      receptor synthesis, frontal cortices of Parkinson patients with cognitive
      dysfunction have been screened for the expression of the nicotinic receptor alpha
      4 subunit gene. Quantitative assessment of alpha 4 mRNA-expressing neurons did
      not show significant differences between patients and controls. Therefore,
      decreased nicotinic receptor sites cannot be attributed to alterations at the
      transcriptional level of the alpha 4 gene. Alternative causes have to be searched
      for at the translational and/or postranslational level.

PMID- 7624022
TI  - Joint-dependent mechanisms to adapt to an imbalance between flexion and extension
      forces in human gait.
AB  - In human gait, alternating leg flexion/extension movements essentially require
      the production of extension muscle forces due to the large contribution of
      passive forces to leg flexion. In this experiment, we studied the adaptive
      capabilities of walking subjects constrained with elastic cords which further
      facilitated leg flexion and impeded leg extension. In order to walk, the subjects
      let the moments created by the elastic cords increase the ankle flexion during
      the whole cycle, which allowed them to reduce part of these moments. By contrast,
      at the knee level, they increased their extension muscle activity to compensate
      for the remaining constraint moments during the swing phase, which resulted in
      unchanged kinematics. Although neuromuscular locomotor synergy is often
      considered to control the lower limb as a unit, we showed here that different
      adaptive mechanisms can act at different joints of the same leg.

PMID- 7624023
TI  - A subset of striatopallidal neurons are Fos-immunopositive following acute
      monoamine depletion in the rat.
AB  - Experiments were conducted to characterise the Fos-immunopositive neurons that
      are observed in the dorsal rim of the striatum following monoamine depletion by
      the systemic administration of reserpine. Using a retrograde tract-tracer, some
      of these neurons could be shown to project to the globus pallidus but none were
      seen to project to the entopeduncular nucleus. In addition, these neurons were
      located in a region of both poor calbindin immunoreactivity and cholinesterase
      activity. It can be concluded that Fos levels are increased only in a subset of
      striatopallidal neurons following monoamine depletion. This subset of neurons is
      located in the dorsal region of the striatum where it has previously been shown
      that neurons can preferentially be induced to undergo apoptosis upon monoamine
      depletion.

PMID- 7624024
TI  - Do the saccadic system and the vestibulo-ocular reflex of monkeys share a common
      neural integrator?
AB  - A common 'neural integrator' has been hypothesized to perform mathematical
      integration of velocity-coded inputs for all oculomotor subsystems. Studies in
      cats suggested that the integrators for some subsystems may be differentially
      affected by drugs. Our tests in macaques show that the fixation is unaffected and
      saccadic and vestibulo-ocular systems are affected in parallel. Thus, the common
      integrator hypothesis cannot be ruled out on the basis of these results.

PMID- 7624025
TI  - Contribution of the sciatic and saphenous nerve to the ventrobasal thalamic
      neuronal responses to pinch in rats with a chronic sciatic nerve constriction: a
      study using anesthetic blocks and nerve section.
AB  - To extend the study on the respective contribution of the sciatic and saphenous
      nerve in abnormal nociceptive responses observed in rats with a loose
      constriction of one sciatic nerve, neuronal responses to pinch applied to the
      territory of the injured nerve, recorded in the ventrobasal complex of the
      thalamus have been studied. Eleven neurones recorded in 11 rats with a nerve
      constriction since 15-19 days and clear abnormal pain-related behaviour to
      mechanical stimulus, were tested before and during an anesthetic block of the
      saphenous and/or of the sciatic nerve, and/or after the saphenous nerve section.
      Only the sciatic nerve block depressed significantly the pinch responses.

PMID- 7624026
TI  - Baclofen inhibits GABAergic transmission after treatment with type-specific
      calcium channel blockers in cultured rat hippocampal neurons.
AB  - Effects of the GABAB agonist baclofen on GABAergic transmission were examined
      before and after treatment with N-type (CgTX) and P-type (AGTX) Ca2+ channel
      blockers in cultured rat hippocampal neurons. Baclofen reduced GABAergic synaptic
      currents (IPSCs) without affecting the postsynaptic sensitivity to GABA. The
      presynaptic inhibition by baclofen was not blocked by Ba2+, a K+ channel blocker.
      IPSCs were reduced by treatment with either CgTX or AGTX, and completely
      abolished by treatment with both toxins. Both IPSCs after treatment with CgTX and
      those after AGTX treatment were similarly reduced by baclofen. The results
      indicate that both the transmission mediated by AGTX-sensitive Ca2+ channels and
      that by CgTX-sensitive Ca2+ channels are sensitive to baclofen, suggesting that
      activation of presynaptic GABAB receptors might inhibit both types of Ca2+
      channels contributing to the GABAergic transmission in the hippocampus.

PMID- 7624027
TI  - Allelic variation of apolipoprotein E in Japanese sporadic Creutzfeldt-Jakob
      disease patients.
AB  - We analyzed apolipoprotein E (apo E) genotypes in 53 Japanese sporadic
      Creutzfeldt-Jakob disease (CJD) patients and 100 normal controls using the
      polymerase chain reaction (PCR) and restriction fragment length polymorphism
      (RFLP) methods. The apo E allelic frequencies in Japanese sporadic CJD patients
      and our control population were as follows: epsilon 2, 6.6% versus 7.5%; epsilon
      3, 82.1% versus 81.5%; epsilon 4, 11.3% versus 11.0%. The mean ages at onset in
      Japanese sporadic CJD patients were as follows: epsilon 3/epsilon 3, 63.8 years;
      epsilon 3/epsilon 4, 66.3 years; epsilon 2/epsilon 3, 68.6 years. These results
      indicate that there is no association between apo E genotype and sporadic CJD in
      Japan.

PMID- 7624028
TI  - The opioid antagonist naloxone does not alter discharges of nociceptive afferents
      from the acutely inflamed knee joint of the cat.
AB  - Recent studies have shown peripheral antinociceptive effects of opiates in
      inflamed tissue. To test whether the afferent activity during an acute
      inflammation may also be suppressed by endogenous opioids, we studied whether the
      application of the opioid antagonist naloxone would alter the afferent discharges
      from the cat knee joint inflamed by kaolin and carrageenin. After i.a. bolus
      administration of naloxone (3 micrograms/kg and 1 mg/kg) close to the joint,
      neither the ongoing activity nor the responses to noxious and innocuous movements
      significantly changed in group III or group IV units. Since naloxone did not
      unmask opioidergic activity under these conditions, we conclude that the
      development of increased activity in joint afferents during an acute
      kaolin/carrageenin-induced inflammation is not tonically suppressed by endogenous
      opioids.

PMID- 7624029
TI  - Mitogenic and antimitogenic effects of pituitary adenylate cyclase-activating
      polypeptide (PACAP) in adult rat chromaffin cell cultures.
AB  - The neurotransmitter, pituitary adenylate cyclase-activating polypeptide (PACAP),
      is present in the rat adrenal medulla and is a potent stimulus for catecholamine
      secretion. Previous studies have suggested that neurally derived signals
      stimulate proliferation of chromaffin cells in adult rats. To determine whether
      PACAP might be involved in mitogenic signalling, its effects on bromodeoxyuridine
      incorporation were studied in adrenal medullary cell cultures from adult female
      rats. Both PACAP 27 and PACAP 38 are able to stimulate proliferation of adult rat
      chromaffin cells in vitro, either alone or in conjunction with PMA, an activator
      of protein kinase C. BrdU-labelled nuclei are observed in both epinephrine and
      norepinephrine cells, and proliferation of both cell types is stimulated by the
      same concentrations of PACAP that elicit secretion of catecholamines. The
      mitogenic effects of PACAP are potentiated by indolidan, a phosphodiesterase
      inhibitor known to cause pheochromocytomas in rats, and are inhibited by H-89, an
      inhibitor of protein kinase A. Mitogenic concentrations of PACAP inhibit
      mitogenic effects of nerve growth factor. These findings support the hypothesis
      that neurally derived signals regulate chromaffin cell proliferation in adult
      rats. Indolidan and a variety of nongenotoxic agents that cause pheochromocytomas
      in rats may do so indirectly by increasing neurally mediated chromaffin cell
      turnover. The antagonism between PACAP and NGF suggests that neurotransmitters
      may supersede growth factors in regulating chromaffin cell proliferation during
      development by suppressing or co-opting portions of growth factor signaling
      pathways.

PMID- 7624030
TI  - Muscarinic cholinergic receptors in dorsal root ganglia of chick embryo: a
      radioligand binding and immunocytochemical study.
AB  - The presence and micro-anatomical localization of muscarinic cholinergic
      receptors were assessed in dorsal root ganglia of chick embryo during development
      using radioligand binding and immunocytochemical techniques, respectively. The
      non-selective muscarinic cholinergic receptor radioligand [3H]quinuclidinyl
      benzilate was specifically bound to sections of chick dorsal root ganglia with a
      dissociation constant value (Kd) of 0.75 +/- 0.02 nM and a maximum density of
      binding sites (Bmax) of 7.2 +/- 0.5 fmol/mg tissue. [3H]Quinuclidinyl benzilate
      binding was partially sensitive to pirenzepine displacement. This suggests that
      muscarinic cholinergic receptors expressed by dorsal root ganglia of chick embryo
      at least in part belong to the M1 muscarinic receptor subtype. Immunocytochemical
      analysis confirmed the presence of muscarinic receptors in the ganglia. These
      findings suggest that neurons of dorsal root ganglia, which are known to express
      cholinergic markers such as choline acetyltransferase, acetylcholinesterase and
      high affinity choline uptake, are also cholinoceptive.

PMID- 7624031
TI  - Superoxide dismutase (glu100-->gly) in a family with inherited motor neuron
      disease: detection of mutant superoxide dismutase activity and the presence of
      heterodimers.
AB  - Superoxide dismutase glu100-->gly, a mutation known to be associated with
      familial motor neuron disease (familial amyotrophic lateral sclerosis) has been
      detected in one symptomatic and five of seven asymptomatic members of a family
      with a history of this disease. On average, the individuals with the mutation had
      75% of normal red blood cell superoxide dismutase activity. Native polyacrylamide
      gels stained for superoxide dismutase activity showed two abnormal bands in the
      family members identified as carrying the mutation. This indicates that active
      mutant enzyme is present in red cells and forms stable homodimers and
      heterodimers with the normal chain. A silent mutation in exon 4, not associated
      with motor neuron disease, was also detected in one family member.

PMID- 7624032
TI  - Experience-dependent maturation of the spatial and temporal characteristics of
      the cell receptive fields in the kitten visual cortex.
AB  - The development of contrast sensitivity to spatial and temporal frequencies was
      studied in the visual cortex of 6-week-old kittens reared from birth in three
      conditions: normal, dark-reared (DR) and dark-reared after 6 h of visual
      experience. Receptive fields of cells recorded in area 17 were quantitatively
      analysed using drifting sine-wave gratings. Compared to the low values obtained
      in the DR kittens, we observed after 6 h of visual experience: (1) an adult-like
      detection of higher spatial frequencies, (2) an increase of contrast sensitivity
      at low temporal frequencies; (3) a shift of the cell optimum towards 3 Hz, all
      values close to the normal ones. Unlike the spatial frequency selectivity,
      contrast sensitivity and detection of higher temporal frequencies continue to
      develop with age and visual experience.

PMID- 7624034
TI  - Localization of the rho 1- and rho 2-subunit messenger RNAs in chick retina by in
      situ hybridization predicts the existence of gamma-aminobutyric acid type C
      receptor subtypes.
AB  - We have amplified partial complementary DNAs for the chicken gamma-aminobutyric
      acid type C (GABAC) receptor rho 1 and rho 2 subunits using the polymerase chain
      reaction. These nucleotide sequences have been utilized to design specific
      oligonucleotide probes for the in situ hybridization localization of the
      corresponding messenger RNAs (mRNAs) in the 1-day-old chick retina. Although both
      transcripts are found almost exclusively in the inner nuclear layer, their
      distributions differ markedly. From the locations of the hybridization signals,
      we deduce that the rho 1-subunit mRNA is present mainly in bipolar cells and that
      the rho 2-subunit mRNA is present in both amacrine and horizontal cells. These
      results suggest that the rho 1 and rho 2 subunits frequently occur in different
      receptor complexes and, therefore, that subtypes of the GABAC receptor exist.

PMID- 7624033
TI  - Developmental expression of GAP-43 and SNAP-25 in heterotopic rat cortical
      grafts.
AB  - In situ hybridization techniques were used to assess (i) whether the temporal
      developmental profiles of the nervous system specific growth associated
      phosphoprotein (GAP-43) and the 25-kDa synaptosomal-associated protein (SNAP-25)
      are maintained in heterotopic cortical transplants, and (ii) whether the
      hybridization intensity in morphologically differentiated heterotopic transplants
      is comparable to that in the cortex of host animals. Cortical primordia at
      embryonic day 14 were stereotactically grafted into the striatum of adult
      recipient rats. Grafts at days 4, 7, 14, 35 and 56 after transplantation
      demonstrated developmental changes with a progressive decline of GAP-43 and a
      continuous up-regulation of SNAP-25 expression. Our data provide evidence of
      distinct molecular alterations during the differentiation process of cortical
      grafts, which are strikingly similar to previous studies investigating the
      temporal profile and intensity of GAP-43 and SNAP-25 gene expression in normal
      developing cortex of the rat.

PMID- 7624035
TI  - Muscarine increases a voltage-independent potassium conductance through an M4
      receptor in rat dorsolateral septal nucleus neurons.
AB  - The direct effect of muscarine on neurons of the rat dorsolateral septal nucleus
      (DLSN) was examined by using conventional microelectrode and voltage-clamp
      techniques. Muscarine (1-50 microM) caused a hyperpolarization accompanied by an
      increase of a voltage-independent potassium conductance. Pirenzepine
      competitively antagonized the muscarine-induced hyperpolarization with an
      apparent dissociation constant (Kd) value of 54 nM. Furthermore, intracellular
      loading with GTP gamma S, a non-hydrolyzable GTP analog, blocked irreversibly the
      muscarine-induced hyperpolarization. In addition, pretreatment of neurons with
      pertussis toxin (PTX) prevented the hyperpolarization produced by muscarine.
      These results suggest that muscarine hyperpolarizes DLSN neurons via a voltage
      independent potassium conductance by acting at M4 subtype receptors which are
      coupled to a PTX-sensitive G-protein in DLSN neurons.

PMID- 7624037
TI  - Nanomolar concentrations of nicotine increase the release of [3H]dopamine from
      rat striatal synaptosomes.
AB  - Nicotine stimulates the release of several neurotransmitters from brain tissue by
      acting on presynaptic nicotinic acetylcholine receptors (nAChR). In this study,
      an in vitro superfusion system was used to measure the nicotine-evoked release of
      [3H]dopamine (DA) from rat striatal synaptosomes. A 2-min exposure to micromolar
      nicotine produces a rapid increase in [3H]DA release. With continued exposure the
      response declines, apparently due to conversion of the nAChRs to a high-affinity
      desensitized conformation. In contrast, prolonged exposure to nanomolar
      concentrations of nicotine, while not producing an immediate response, leads to a
      gradual cumulative enhancement in [3H]DA release. This effect is calcium
      dependent and blocked by the nicotinic antagonist, dihydro-beta-erythroidine. It
      is suggested that the gradual DA release in response to low concentrations of
      nicotine occurs as a result of either open channel properties of the desensitized
      receptor or an equilibrium between the high-affinity desensitized and active
      states of the nAChRs.

PMID- 7624038
TI  - The neuroprotective effect of high-dose methylprednisolone in rat spinal cord
      hemisection.
AB  - Multiple studies support a neuroprotective effect for high-dose
      methylprednisolone (MP) in acute blunt spinal cord injury. We know of no study
      that addresses the role of MP in prophylaxis for surgical trauma to the spinal
      cord or for the treatment of non-missile penetrating injuries to the spinal cord.
      We examined the neuroprotective effect of MP as measured by the retrograde
      transport of the fluorescent tracer Fluoro-Gold in 20 rats undergoing C-2
      hemisection. Mean cell counts of retrogradely labeled rubrospinal neurons were
      determined 1 week post-injury. The group receiving MP had a significantly higher
      (P < 0.0001) number of labeled cells (x = 594) compared to controls (x = 387).
      The highly significant increase in mean cell counts in rats receiving steroids
      suggests less secondary axonal injury in the MP group. These findings are the
      first report of a neuroprotective effect of MP in rat spinal cord hemisection. We
      suggest that MP may be beneficial as prophylaxis during planned or incidental
      surgical trauma to the spinal cord and after non-missile penetrating injuries to
      the spinal cord.

PMID- 7624036
TI  - Monoclonal antibody AT8 recognises tau protein phosphorylated at both serine 202
      and threonine 205.
AB  - Hyperphosphorylated microtubule-associated protein tau is the major component of
      the paired helical filament of Alzheimer's disease. Phosphorylation-dependent
      anti-tau antibodies are being used to identify specific amino acids that are
      phosphorylated in tau from normal brain and Alzheimer's disease brain. As such,
      monoclonal antibody AT8 is widely used. By a combination of site-directed
      mutagenesis of recombinant tau and in vitro phosphorylation, we show that AT8
      requires tau protein to be phosphorylated at both serine 202 and threonine 205
      (using the numbering of the longest human brain tau isoform.

PMID- 7624039
TI  - Catecholaminergic neurons in the nucleus tractus solitarii which send their axons
      to the midbrain periaqueductal gray express Fos protein after noxious stimulation
      of the stomach: a triple labeling study in the rat.
AB  - In rats which were injected with horseradish peroxidase (HRP) into the midbrain
      periaqueductal gray (PAG) and then administered with formaldehyde into the
      stomach, Fos-like immunoreactivity was found in tyrosine hydroxylase-like
      immunoreactive neurons in the nucleus tractus solitarii (NTS) which were
      retrogradely labeled with HRP. The results indicate that catecholaminergic NTS
      neurons may mediate nociceptive visceral information to the PAG.

PMID- 7624040
TI  - Apolipoprotein E4 allele frequency in Spanish Alzheimer and control cases.
AB  - We have found an APOE epsilon 4 allelic frequency of 0.289 (95% CI 0.195-0.383)
      in Spanish AD patients (n = 88; average age = 71.2 +/- 9.37) and of 0.061 (95% CI
      0.023-0.099) in age-matched controls (n = 147; average age = 71.5 +/- 10.29).
      Remarkably no ApoE 4/4 subjects were observed in any of the age-matched control
      groups compared to a total of 22 AD patients with the ApoE 4/4 phenotype. The
      combined odds ratio for subjects with one or two epsilon 4 alleles in the present
      study is 6.25 (95% CI 3.13-12.60), which is one of the highest so far reported.
      Altogether our results suggest a trans-European difference in the ApoE epsilon 4
      frequency but no differences in the strength of the association between APOE4 and
      AD.

PMID- 7624041
TI  - The response to isoproterenol of synaptic ribbon numbers in the rat pineal gland
      changes during postnatal development.
AB  - In the mammalian pineal gland synaptic ribbons (SRs) are dynamic organelles of
      pinealocytes undergoing a day/night rhythm, with small numbers during daytime and
      significantly higher numbers at night, similar to the formation of the pineal
      hormone melatonin. Whereas the day/night rhythm of melatonin synthesis is
      adrenergically regulated, data on the adrenergic regulation of SR numbers in the
      rat pineal gland are at variance. While some authors have demonstrated that
      isoproterenol (ISO) stimulates SR numbers, others could not find any effect. To
      clarify the issue, we carried out identical experiments in two age groups. It was
      found that in male Sprague-Dawley rats, administration of the beta-adrenergic
      agonist ISO (2.5 or 10 mg/kg body weight) increased SR profile numbers in one age
      group (3 weeks), but not in the other (8 weeks). These findings resolve the
      apparent discrepancy reported in the literature, by showing that the response to
      ISO of SR profile numbers is apparently lost during postnatal differentiation of
      the pineal gland.

PMID- 7624042
TI  - N-Methyl-D-aspartate receptor subunits NR1 and NR2C are overexpressed in the
      inferior colliculus of audiogenic mice.
AB  - Some non-DBA2 Albino Swiss mice exhibit noise induced epileptic seizures during a
      short period of postnatal development. Because N-methyl-D-aspartate (NMDA)
      glutamate ionotropic receptors are involved in the occurrence of audiogenic
      seizures, we investigated by in situ hybridization methods, the expression of the
      different subunits (NR1, NR2A, NR2B, NR2C) of this receptor in the central
      nucleus of the inferior colliculus (IC), a main relay of the auditory pathways.
      At postnatal day 20, the NR2C subunit is highly expressed in the IC of convulsive
      mice, while in non-convulsive mice a slight signal is only found for NR1, NR2A,
      and NR2B. In adult mice, the NR1 and NR2A signals are observed while the NR2B
      signal is almost undetectable. The audiogenic susceptibility may be related to
      the transient expression of the NR2C subunit during a brief neonatal period
      during which synaptic reorganization happens.

PMID- 7624043
TI  - Skeletofusimotor (beta) innervation of proximal and distal forelimb muscles of
      the cat.
AB  - The innervation of muscle spindles by skeletofusimotor (beta) axons has been
      compared in two long digit extensor muscles with three elbow extensor muscles of
      the cat forelimb. The proportion of muscle spindle poles with p1-endplates was
      analysed in silver impregnated teased material. The proximal and distal muscles
      displayed a significant difference in their proportion of muscle spindle poles
      with p1-endplates. The distal muscles had an estimated proportion of more than
      70% beta innervation of their muscle spindles, the proximal muscles of 41-47%.
      This difference is discussed with respect to the different circuitry of the
      motoneurones. We suggest that the high proportion of beta-innervated spindles in
      distal muscles obtained with the absence of a recurrent inhibitory system in the
      innervating motoneurones [18] serves the execution of manipulative movements.

PMID- 7624044
TI  - Effect of dietary NaCl on tyrosine hydroxylase in the superior cervical ganglia
      of Dahl rats.
AB  - To investigate the involvement of peripheral catecholamines in the development of
      Dahl-Iwai salt-sensitive (DIS/Eis) hypertension, we performed immunohistochemical
      staining of tyrosine hydroxylase (TH) in the superior cervical ganglia (SCG) of
      DIS/Eis rats and Dahl-Iwai salt-resistant (DIR/Eis) rats, and in situ
      hybridization histochemistry for demonstration of TH mRNA localization in the SCG
      of these rats. DIS/Eis and DIR/Eis rats were fed on a high (8%) salt diet or on a
      low (0.3%) salt diet for 4 weeks. Nerve cells in the SCG of DIS/Eis high salt
      rats exhibited more intense TH-immunoreactivity (P < 0.01) and hybridization
      signals (P < 0.01) than those of the other experimental groups. These findings
      suggest that activation of peripheral sympathetic nerves may account for
      hypertension in DIS/Eis rats on a high salt diet.

PMID- 7624045
TI  - Nigrostriatal dopamine system mediates baroreflex sensitivity in rats.
AB  - Both sham-operated rats and rats with lesions of the nigrostriatal dopamine (DA)
      pathway were subjected to increasing or decreasing carotid sinus pressure
      (respectively produced by phenylephrine injection or bilateral carotid occlusion)
      and their striatal DA release and baroreflex responses were compared. In sham
      operated rats, phenylephrine produced both increased striatal DA release and
      decreased heart rate, while bilateral carotid occlusion produced the opposite
      effects. Both the striatal DA release and baroreflex responses produced by
      phenylephrine or carotid occlusion were attenuated by lesions of the
      nigrostriatal DA pathway induced by intramedial forebrain bundle injection of 6
      hydroxydopamine. The data indicate that the nigrostriatal DA pathway mediates
      baroreflex sensitivity in rats.

PMID- 7624046
TI  - Activated microglia cause superoxide-mediated release of iron from ferritin.
AB  - Ferritin contains the greatest part of the iron found in the brain, and the
      release of iron stores from ferritin has an essential role in iron-dependent
      lipid peroxidation. We examined the effect of cultured microglia on iron
      mobilization from ferritin. Microglia stimulated by phorbol myristate acetate
      caused the release of iron from ferritin, which was detected by monitoring iron
      ferrozine complex formation. This iron mobilization was mediated by microglial
      superoxide production, as evidenced by the significant inhibitory effect of
      superoxide dismutase. The role of superoxide was also supported by the close
      correspondence of cumulative microglial superoxide production, as demonstrated by
      the MCLA (Cypridina luciferin analogue)-dependent chemiluminescence assay, to the
      time course of iron release from ferritin. Iron release induced by activated
      microglia may be partly responsible for the oxidative damage that is thought to
      occur in Parkinson's disease and other neurodegenerative disorders.

PMID- 7624047
TI  - Acetylcholinesterase induces long-term potentiation in CA1 pyramidal cells by a
      mechanism dependent on metabotropic glutamate receptors.
AB  - Acetylcholinesterase (AChE) has additional functions within the central nervous
      system that are unrelated to cholinergic transmission. In the cerebellar cortex
      AChE has been shown to potentiate synaptic responses evoked by excitatory amino
      acids. Because AChE is also secreted from the terminal regions of cholinergic
      nerves within the hippocampus, this study investigates the actions of AChE on
      synaptic transmission in guinea pig hippocampal slices. Application of AChE
      produced a long-lasting potentiation of both the field epsp and the resulting
      population spike evoked by stimulation of the Schaffer/commissural-CA1 pathway.
      This effect was independent of any cholinergic receptor stimulation since it
      persisted in the presence of the cholinergic antagonists atropine and
      mecamylamine. Furthermore, the effect was not mimicked by butyrylcholinesterase
      despite its cholinolytic activity. However, the effect of AChE was dependent on
      metabotropic glutamate receptor stimulation since it was prevented by the
      metabotropic receptor antagonist (+/-)-alpha-methyl-4-carboxyphenylglycine.
      Perfusion with AChE therefore induces a long-lasting potentiation of hippocampal
      synaptic transmission which is reminiscent of the classical LTP produced by
      tetanic stimulation. Consequently the secreted protein could play an important
      role in the molecular mechanisms of learning and memory in vertebrates.

PMID- 7624048
TI  - Inhibition of nitric oxide synthesis potentiates the responsiveness of carotid
      chemoreceptors to systemic hypoxia in the rat.
AB  - Carotid sinus nerve afferent activity was recorded in the peripheral end of the
      cut carotid sinus nerves in rats anesthetized with urethane, paralyzed and
      artificially ventilated with pure oxygen in order to abolish any resting
      chemoreceptor activity. Hypoxic stimuli were applied by switching pure oxygen to
      a nitrogen/oxygen gas mixture in the inspiratory line, reducing end-tidal oxygen
      concentrations to 10% FETO2, 8% FETO2 and 6% FETO2 respectively. Each stimulus
      was applied for 60 s and ventilation was switched again to pure oxygen. Increases
      in the carotid sinus nerve activities were due to chemo- and not to baroreceptor
      stimulation as arterial blood pressure decreased during hypoxia. After
      administration of nitric oxide synthase blocker L-NG-nitroarginine methyl ester,
      30 mg/kg weight i.v., chemoreceptor excitatory response to all hypoxic stimuli
      increased significantly. Subsequent administration of L-arginine, 300 mg/kg
      weight i.v., restored chemoreceptor response to hypoxia to initial magnitude. It
      is concluded that NO is generated in the carotid body and attenuates
      chemoreceptor responsiveness in rats in vivo, as reported on isolated carotid
      bodies in cats in vitro.

PMID- 7624049
TI  - Possible involvement of botulinum ADP-ribosyltransferase sensitive low molecular
      G-protein on 5-hydroxytryptamine (5-HT)-induced inositol phosphates formation in
      5-HT2c cDNA transfected cells.
AB  - To clarify the involvement of botulinum ADP-ribosyltransferase sensitive low
      molecular G-proteins in 5-hydroxytryptamine (5-HT)-induced stimulation of
      phosphatidylinositol turnover, we examined the effects of 5-HT on inositol
      phosphates formation in COS 7 cells transfected with 5-HT2c receptor cDNA, but
      did not in non-transfected or vector-transfected cells. A typical 5-HT2c receptor
      antagonist mianserin (0.3-3 microM) inhibited the 5-HT-induced inositol
      phosphates formation. Treatment with botulinum toxin D preparation (20
      micrograms/ml, 8 h) that contained botulinum C3 ADP-ribosyltransferase, blocked
      the 5-HT-induced inositol phosphate formation, although botulinum toxin A
      preparation that did not contain the enzyme did not have an influence. These
      results support our previous findings suggesting that low molecular weight G
      proteins ADP-ribosylated by botulinum ADP-ribosyltransferase are involved in
      phospholipase C activity.

PMID- 7624050
TI  - Serotonin reduces synaptic excitation of principal cells in the superficial
      layers of rat hippocampal-entorhinal cortex combined slices.
AB  - The cells of the entorhinal cortex receive a dense innervation of serotonergic
      fibres from the Raphe nuclei and express a high density of 5-hydroxytryptamine 1A
      (5-HT1A) receptors. We investigated the effects of serotonin on excitatory
      synaptic transmission in principal cells from entorhinal cortex layers II and III
      within hippocampal-entorhinal cortex combined slices. Although serotonin had an
      effect upon the membrane conductance of some, but not all cells, its most
      pronounced action was to reduce stimulus evoked excitatory synaptic potentials
      and currents (EPSP/Cs). Both alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic
      acid and N-methyl-D-aspartate receptor-mediated EPSPs were reduced to similar
      extents over a range of concentrations. Since the principal cells in layer II and
      layer III are the main projection cells of the entorhinal cortex, these
      inhibitory effects of serotonin may have implications for the transfer of
      information to the hippocampus.

PMID- 7624051
TI  - Central nervous system neurons identified after injection of pseudorabies virus
      into the rat clitoris.
AB  - Transneuronal tracing techniques were used to identify putative spinal and brain
      neurons involved in the efferent control of the clitoris. Pseudorabies virus was
      injected into the rat clitoris and virus-labeled neurons were identified
      immunohistochemically. Neurons were found primarily in L5-S1 segments of the
      spinal cord. In addition, virus-labeled cells were found in T12-L4 and S2-S4. In
      the brain, virus-labeled cells were found in the nucleus paragigantocellularis,
      raphe pallidus, raphe magnus, Barrington's nucleus, ventrolateral central gray,
      hypothalamus and medial pre-optic region. These data identify a multisynaptic
      circuit of neurons which may be involved in clitoral control.

PMID- 7624052
TI  - Olivary projecting neurons in the nucleus prepositus hypoglossi, group y and
      ventral dentate nucleus do not project to the oculomotor complex in the rabbit
      and the rat.
AB  - The nucleus prepositus hypoglossi, dorsal group y, ventral dentate nucleus, and
      medial vestibular nucleus all project to both the oculomotor complex and inferior
      olive. In the present study, we demonstrate with the use of retrograde double
      labeling techniques in rabbits and rats, that the neurons in these pre-oculomotor
      nuclei that project to the inferior olive are intermingled with those that
      project to the oculomotor nucleus, but that virtually none project to both.

PMID- 7624053
TI  - Expression of Rb, E2F1, cdc2, and D, and B cyclins in developing spinal cord.
AB  - The spatial and temporal distribution of transcripts for the tumor suppressor
      gene Rb, transcription factor E2F1, cdc2 kinase, cyclins D1, D2, B1 and B2 during
      neurogenesis of the spinal cord was determined by in situ hybridization. The Rb
      and E2F1 transcripts were detectable in proliferating and differentiating cells.
      By contrast, cdc2, cyclins D1, B1 and B2 are expressed in the ventricular zone
      where proliferating cells are localized. Cyclin D2 mRNA was detectable only in
      the marginal zone of the developing neural tube. Electrophoretic mobility shift
      analyses demonstrated a changing pattern of DNA/protein complexes that bind to
      E2F binding site. These observations suggest that Rb and E2F1 may be involved in
      the early stages of neuronal differentiation in addition to the cell cycle
      regulation.

PMID- 7624054
TI  - Motor programming in both hemispheres: an EEG study of the human brain.
AB  - Differential hemispheric involvement in controlling simple and complex motor
      movements was investigated in humans using EEG spectral responses. Analysis of
      spectral power in the alpha band revealed the following. While during a simple
      motor task (tapping) signs of unilateral cortical activation were present, more
      complex sequential motor behaviour (Luria finger apposition task) led to
      symmetrical bihemispheric activation. It appears that unilateral cortical
      processing is present in the normal brain when very simple computations are
      performed. Bilateral hemispheric activity and interhemispheric interaction may be
      general features of more complex information processing in the cortex.

PMID- 7624055
TI  - Muscarinic receptor modulation of acetylcholine release from rat cerebral cortex
      and hippocampus.
AB  - An attempt to identify the muscarinic receptor subtypes involved in presynaptic
      modulation of acetylcholine (ACh) release from cortical and hippocampal slices
      was made by means of several muscarinic antagonists. Cortical and hippocampal
      slices prepared from adult rats were superfused with Krebs solution containing
      physostigmine; ACh content of the superfusate at rest and after electrical
      stimulation (1 Hz) was quantified by high performance liquid chromatography. The
      antagonists were added to the Krebs at the concentration of 1 microM. ACh release
      at rest was enhanced only in the cortex by (+/-)-5,11-dihydro-11-([(2-[2
      [(dipropylamino)methyl]-1- piperidinyl)ethyl)amino]carbonyl)-6H-pyrido[2,3
      b](1,4)- benzodiazepine-6-one (AFDX384), an M2/M4 selective antagonist. The
      evoked ACh release from the cerebral cortex was significantly increased by
      AFDX384, methoctramine, pirenzepine, M2/M4, M2 and M1 selective antagonists,
      respectively, and scopolamine. This finding suggests that M1, M2 and M4
      presynaptic receptor subtypes could regulate evoked ACh release in the cortex. In
      hippocampal slices, the evoked ACh release was enhanced by AFDX384, pirenzepine
      and scopolamine but not by methoctramine. In this region ACh release seems
      therefore regulated only by M1 and M4 receptor subtypes. The M3 antagonist (+/-)
      p-fluorohexahydro-sila-difenidol hydrochloride did not affect ACh release.

PMID- 7624056
TI  - Enkephalinergic and catecholaminergic neurons constitute separate populations in
      the rat Kolliker-Fuse/A7 region.
AB  - Using a double-labeling immunohistochemical and in situ hybridization technique
      for the simultaneous detection of tyrosine hydroxylase and preproenkephalin mRNA,
      we demonstrate that catecholaminergic and enkephalinergic neurons in the Kolliker
      Fuse nucleus (K-F)/A7 region in the dorsolateral pons constitute separate
      populations. The enkephalinergic cell group is much larger than the
      catecholaminergic cell group. Most of the enkephalinergic neurons are located
      caudal to the catecholaminergic neurons, but enkephalinergic neurons are also
      interspersed among the catecholaminergic neurons. Taken together with previous
      demonstrations that the enkephalinergic neurons in K-F give rise to descending
      projections to the ventrolateral medulla and spinal cord, the current
      observations suggest that the antinociceptive effects that result from electrical
      stimulation of K-F may be a consequence of the activation of enkephalinergic
      neurons, either alone or in conjunction with catecholaminergic neurons.

PMID- 7624057
TI  - Down-regulation of the nocturnally elevated guanylyl cyclase activity in the rat
      pineal gland.
AB  - Previous studies have shown that in the rat pineal, the cytosolic and the
      particulate forms of guanylyl cyclase (GC) activity undergo a biphasic 24-h
      rhythm with two prominent peaks, one in the middle of the light phase and the
      other in the middle of the dark phase. In this study we investigated whether the
      well established photo-neural adrenergic regulatory processes identified for
      pineal melatonin synthesis also apply to the nocturnal elevation of GC activity.
      A 10-min light pulse given in the middle of the dark phase decreases the
      cytosolic and the particulate forms of GC. Administration of the beta-receptor
      blocker propranolol did not depress the nocturnally elevated GC activity.
      Sympathetic denervation of the pineal gland by means of superior cervical
      ganglionectomy did not noticeably affect nocturnal GC activity studied 6 days and
      2 months after surgery. In vitro, administration of the nitric oxide synthase
      blocker NG-mono-methyl-L-arginine (NMMA) for 10 min did not change the cytosolic
      form of GC activity. The results obtained reveal that in the rat pineal, the down
      regulation of the nocturnally elevated GC activity does not appear to be
      adrenergically mediated.

PMID- 7624058
TI  - Human cerebrovascular nerve fibers immunoreactive for synaptophysin, chromogranin
      A and tyrosine hydroxylase.
AB  - The innervation of human cerebral blood vessels has been examined using
      synaptophysin, a marker of synaptic vesicles, and chromogranin A, a marker of
      large dense-core vesicles. The catecholaminergic marker tyrosine hydroxylase was
      used for comparison. Synaptophysin and tyrosine hydroxylase demonstrated a
      similar distribution of nerve fibers whereas chromogranin A terminals were only
      sparsely evident. Our results suggest that there is not a subset of nerve fibers
      in existence which has a distribution different than that of catecholaminergic
      fibers. Furthermore, in view of its unexpected sparse distribution, chromogranin
      A in the nervi vasorum is not likely to be a significant contributor to cerebral
      blood flow regulation.

PMID- 7624059
TI  - Synaptotagmin I and 1B4 are identical: implications for synaptotagmin
      distribution in the primate brain.
AB  - We have determined that the human cDNA sequence of the previously described
      primate brain mRNA species 1B4 is nearly identical (99.95% similarity) to that of
      human Synaptotagmin I. The apparent identity of Synaptotagmin I with 1B4, whose
      distribution in the brain of the monkey Cynomolgous was determined previously by
      Northern blot and in situ hybridization (ISH) analyses, reveals the Synaptotagmin
      I is differentially expressed in the primate brain. Primate Synaptotagmin I mRNA
      is enriched in hindbrain structures relative to forebrain structures by Northern
      blot analysis. By ISH analysis, primate Synaptotagmin I mRNA is highly expressed
      in occipital cortex and lateral geniculate (visual system components) and
      differentially expressed across topographic cortical boundaries between inferior
      and superior temporal gyrus (a polymodal zone with visual, auditory and
      somatosensory inputs) and between areas 17 and 18 of the visual cortex (primary
      and secondary visual areas). Cortical expression is also enriched in layers V and
      VI, which contain large pyramidal projection neurons. Synaptotagmin I's greater
      association with large projection neurons and with some components of visual
      sensory transduction could reflect a requirement of these neural components for
      greater synaptic activity. Synaptotagmin I expression in the primate brain is
      also dissimilar to Synaptotagmin I expression in rodents. Thus, variation of
      Synaptotagmin I expression has occurred during mammalian evolution, perhaps as a
      consequence of the larger size and neurotransmitter requirements of primate
      neurons.

PMID- 7624060
TI  - New insights into intravenous peptide metabolism.
AB  - A new study of the possible advantages of each of the eight dipeptides for
      intravenous nutrition focuses on kinetics of tyrosine and glutamine injected
      intravenously. Tyrosine and glutamine are two of the three amino acids that are
      difficult to use directly in the preparation of nutrient solutions due to low
      solubility (tyrosine) and limited stability during autoclaving or storage
      (glutamine).

PMID- 7624061
TI  - Food labeling: a Canadian and international perspective.

PMID- 7624062
TI  - Conjugated dienoic linoleate: a polyunsaturated fatty acid with unique
      chemoprotective properties.
AB  - Conjugated dienoic linoleate (CLA), a linoleic acid derivative, has received
      considerable attention as a chemoprotective agent in the past few years because
      it has been shown experimentally to inhibit rat mammary tumorigenesis, mouse
      forestomach neoplasia, and mouse skin carcinogenesis. CLA has several unique
      structural and functional properties resulting in chemical and physiological
      effects that are different from those of all-cis, nonconjugated polyunsaturated
      fatty acids. In turn, these unique qualities appear to modulate cellular
      processes involved in carcinogenesis. This review will introduce the chemical
      background of conjugated dienoic linoleate, examine findings describing its
      chemoprotective qualities, present possible mechanisms of chemoprotection, and
      correlate the possible significance of dietary CLA modulation to carcinogenesis
      to humans.

PMID- 7624063
TI  - Urban nutrition in developing countries.
AB  - In developing countries, the past decades have seen a marked demographic shift
      from rural to urban. By the year 2000, 40% of the population of the Third World
      will live in urban areas. We have limited specific knowledge of the similarities
      and differences in diet, nutrition status, and health effects of diet and
      lifestyle between the traditional rural populations and the emerging urban poor.
      Such information will be useful for basic descriptive information as well as for
      assistance in the design and execution of health and nutrition projects for the
      urban poor.

PMID- 7624064
TI  - Ornithine oxoglutarate therapy improves nutrition status.
AB  - Ornithine oxoglutarate (OGO) has been previously demonstrated to improve
      nutrition status in burn and trauma patients. Recently, OGO supplementation was
      shown to improve nutrition status, ameliorate quality of life, and reduce health
      care costs when given to elderly patients soon after discharge from the hospital.

PMID- 7624065
TI  - Retinol transport and metabolism in transthyretin-"knockout" mice.
AB  - Mice were made deficient in transthyretin (TTR), the protein that normally
      transports plasma retinol complexed with retinol-binding protein (RBP), by
      targeted mutagenesis (TTR-knockout mice). The TTR- mice were healthy and fertile,
      despite extremely low plasma retinol and RBP levels (6% of wild type).
      Circulating retinoic acid was 2.3 times that of wild-type controls. Liver levels
      of RBP were 60% higher in the TTR-mutants compared to wild-type mice, suggesting
      that lack of TTR may block secretion of RBP-retinol from liver.

PMID- 7624066
TI  - Peaceful passing.

PMID- 7624068
TI  - Testing stool for occult blood.

PMID- 7624067
TI  - Myths & facts.

PMID- 7624069
TI  - Detecting the dangers of meperidine.

PMID- 7624070
TI  - Interpreting ECG waveform components.

PMID- 7624072
TI  - Recognizing a potassium imbalance.

PMID- 7624071
TI  - Randy proposes a toast.

PMID- 7624074
TI  - Delivering medications with speed and accuracy.

PMID- 7624073
TI  - The last good-bye.

PMID- 7624075
TI  - Taking a close look at laparoscopy.

PMID- 7624077
TI  - Avoiding vasopressor extravasation.

PMID- 7624076
TI  - Understanding the value of dual oximetry.

PMID- 7624078
TI  - Understanding renal disorders.

PMID- 7624080
TI  - How to protect your older patient from the hazards of polypharmacy.

PMID- 7624079
TI  - Tachycardia: restoring a normal heart rate.

PMID- 7624081
TI  - Managing the "miracle man".

PMID- 7624082
TI  - Job security: clearing away the myths.

PMID- 7624083
TI  - Supporting the families of cancer patients.

PMID- 7624084
TI  - Guarding against aspiration complications.

PMID- 7624085
TI  - Close-up on oncogenes.

PMID- 7624086
TI  - Applying perianal pouches with confidence.

PMID- 7624087
TI  - Macular degeneration: helping your patient cope.

PMID- 7624088
TI  - What's wrong with this patient? Assessing altered level of consciousness.

PMID- 7624089
TI  - Questions to go: what to ask a travel nursing agency before you sign on the
      dotted line.

PMID- 7624090
TI  - Hassle-free licensing.

PMID- 7624091
TI  - What I didn't tell Bob.

PMID- 7624092
TI  - Don't miss the boat--use peer review.

PMID- 7624093
TI  - The case for pediatric dentistry.

PMID- 7624094
TI  - Another way to split fees.

PMID- 7624096
TI  - The cruelest cut.

PMID- 7624095
TI  - Second opinion.

PMID- 7624097
TI  - "No" to legal panel.

PMID- 7624098
TI  - Rethinking the rules.

PMID- 7624099
TI  - Peer review. It's good for dentists and patients.
AB  - A significant member benefit offered by organized dentistry is peer review. DSSNY
      President Henry Gaines refers to peer review as "the crown jewel" of the
      Society's programs. Indeed, dental societies throughout the country look to
      DSSNY's peer review program as a model for how to provide quality assurance to
      patients and the profession.

PMID- 7624101
TI  - For the record. Understanding patient recordkeeping.
AB  - Patient recordkeeping is a vast and complex topic. However, by knowing the basics
      and following the path of least risk, a dentist will find that many practice
      problems and unwanted complications disappear. The article here explains what the
      patient record is; why it is maintained and for how long; what it should or
      should not contain; how to dispose of the record upon retirement, sale of a
      practice or death, and what to do when a patient wants a copy of the record.

PMID- 7624100
TI  - Prevention of dry socket with clindamycin. A retrospective study.
AB  - Clindamycin and other agents were compared for efficacy in preventing the entity
      "dry socket." A total 765 patients were treated with clindamycin, per os, and 408
      patients were treated with other antibiotics or were non-treated controls. All
      patients underwent surgical removal of impacted mandibular third molars. The
      incidence of dry socket in untreated control and in non-clindamycin antibiotic
      treated patients varied from 15 to 31 percent, while in those patients receiving
      clindamycin, the incidence was 0.65 percent. The results demonstrate a remarkable
      effectiveness of clindamycin in reducing the incidence of dry socket following
      surgical removal of impacted mandibular third molar.

PMID- 7624102
TI  - Stress and dentistry. Better practice through control.
AB  - It's impossible to give a single definition to stress. That's because people
      experience it in different ways. It is possible, however, to get it and keep it
      under control. In fact stress-control is necessary to every successful dental
      practice.

PMID- 7624103
TI  - Periodontal lesions absent in HIV-positive children.

PMID- 7624104
TI  - The role of bone scintigraphy in the investigation of patients with low back
      pain.

PMID- 7624105
TI  - 99Tcm-sestamibi as an agent for imaging P-glycoprotein-mediated multi-drug
      resistance: in vitro and in vivo studies in a rat breast tumour cell line and its
      doxorubicin-resistant variant.
AB  - Multi-drug resistance mediated by the transmembrane pump P-glycoprotein (Pgp) is
      an important mechanism of resistance of certain tumours against chemotherapeutic
      drugs. The myocardial perfusion imaging agent 99Tcm-sestamibi is a substrate for
      Pgp. Further characterization of 99Tcm-sestamibi has now been carried out in the
      transplantable rat breast adenocarcinoma cell line, MatB, and its doxorubicin
      resistant variant, AdrR. In vitro accumulation of the tracer in wild-type (WT)
      MatB was high and was not affected by the Pgp modulator, PSC833. Conversely, AdrR
      cells did not accumulate significant amounts of tracer unless PSC833 was present.
      Imaging studies in rats bearing MatB-WT and AdrR tumours showed that 99Tcm
      sestamibi washed out of the resistant tumours at three times the rate of WT
      tumours. These results support the potential use of 99Tcm-sestamibi for
      functional imaging of Pgp activity in patients undergoing chemotherapy.

PMID- 7624106
TI  - SPET imaging of intracranial tumours with 99Tcm-sestamibi.
AB  - Single photon emission tomography (SPET) employing 99Tcm-sestamibi (MIBI)
      injected intravenously was performed in 27 patients for pre-surgical evaluation
      of intraparenchymal brain tumours. A computerized tomography (CT) scan was
      performed in 26 patients, magnetic resonance imaging (MRI) in 8 patients and
      digital subtraction angiography (DSA) in 14 patients. Visual analysis of the SPET
      scans was performed using a 4-point scale relating to background activity, to
      evaluate MIBI uptake in the tumour. The vascular supply and the cellular
      component were also evaluated using DSA and CT scans. In normal controls, MIBI
      uptake was observed in the scalp, in the choroid plexus and in the pituitary
      gland, but never in normal parenchyma. Among the astrocytoma group of patients, a
      trend between MIBI uptake and grade of tumour was noted. MIBI uptake in
      meningiomas depends primarily on the vascular supply. Our results support the
      hypothesis that vascular supply, integrity of the blood-brain barrier, the degree
      of malignancy of the neoplasm and the viability of the tumour cells may be
      related to MIBI uptake.

PMID- 7624107
TI  - Morphology-oriented analysis of cerebral SPET using matched magnetic resonance
      images.
AB  - Complementary morphological information is a prerequisite for the detailed
      analysis of cerebral SPET studies. We therefore developed a technique which
      allows the alignment of SPET and magnetic resonance scans by imaging identical
      slices using external landmarks on an individually fitted mask and subsequent two
      dimensional image processing for in-plane matching. Regional analysis of tracer
      activities can be performed directly on the superimposed SPET and MR outline
      images or by tracing a region of interest on the original MR scan with a parallel
      display on the matched SPET image, and vice versa. Tests assessing correct in
      plane alignment using MRI, inter- and intra-variability of the matching
      procedure, and its comparability with an objectively determined best-matching
      position, confirmed the feasibility, accuracy and usefulness of this procedure.

PMID- 7624108
TI  - Abnormal regional benzodiazepine receptor uptake in the prefrontal cortex in
      patients with panic disorder.
AB  - The neuroanatomical networks involved in the initiation of panic attack and the
      maintenance of panic disorder are poorly understood. This study aimed to
      elucidate the possible abnormalities in benzodiazepine receptor uptake in the
      brain of patients with panic disorder. Seventeen unmedicated patients with panic
      disorder were investigated using 123I-iomazenil single photon emission tomography
      (SPET). Seventeen healthy age- and sex-matched volunteers served as controls. The
      SPET scan was taken 90 min after injection of tracer. Eleven of 17 patients (65%)
      showed an increased (> 2 S.D. higher than the mean of the controls) right-to-left
      ratio of benzodiazepine receptor uptake in the prefrontal cortex. Also, the mean
      right-to-left ratio of benzodiazepine receptor uptake in all 17 patients with
      panic disorder was higher than in the controls (P < 0.001). Our SPET study
      demonstrated focally altered benzodiazepine receptor uptake in the prefrontal
      cortices in patients with panic disorder. Magnetic resonance imaging indicated
      that the affected region was located in the right middle and inferior frontal
      gyri. The deterioration in information processing in the right prefrontal cortex
      may be implicated in the generation of panic disorder.

PMID- 7624109
TI  - The effect on diagnostic quality of using dual isotope imaging for 81Krm
      ventilation and 99Tcm-MAA perfusion lung scanning.
AB  - It is the practice in some centres to use dual isotope imaging to reduce imaging
      times in lung ventilation and perfusion studies with 81Krm gas and 99Tcm
      macroaggregated albumin (99Tcm-MAA) by simultaneous acquisition of the two
      images. The resulting loss of image caused by cross-talk between the two energy
      windows was investigated using two phantoms, one with cold 99Tcm lesions of
      varying size and contrast, and the other a uniform field of 81Krm. It was found
      that, under scatter conditions typical of a patient study, the use of dual
      isotope acquisition and a krypton generator of 470 MBq or greater resulted in a
      perceptible loss of image quality with lesions up to 4 cm in diameter being
      missed. On an older camera system, without modern energy and linearity correction
      facilities, a lower generator activity of only 120 MBq was sufficient to cause
      image degradation even under very low scatter conditions. Seventy-five patient
      studies were performed using both single and dual isotope imaging with generator
      activities ranging from 80 to 282 MBq. At these low generator activities, the
      studies did not demonstrate any differences between the images that would result
      in a different diagnosis. We conclude that the use of dual isotope V/Q scanning
      reduces the diagnostic value of the perfusion image if the activity of the 81Krm
      generator is too high, although at generator activities of 300 MBq or less no
      loss of image quality will occur on modern camera systems.

PMID- 7624110
TI  - Is computer-aided interpretation of 99Tcm-HMPAO leukocyte scans better than the
      naked eye?
AB  - In order to compare visual interpretation of inflammation detected by leukocyte
      scintigraphy with that of different computer-aided quantification methods, 34
      patients (25 with ulcerative colitis and 9 with endoscopically verified non
      inflamed colonic mucosa), were investigated using 99Tcm-hexamethylpropyleneamine
      oxime (99Tcm-HMPAO) leukocyte scintigraphy and colonoscopy with biopsies.
      Scintigrams were obtained 45 min and 4 h after the injection of labelled cells.
      Computer-generated grading of seven colon segments using four different methods
      was performed on each scintigram for each patient. The same segments were graded
      independently using a 4-point visual scale. Endoscopic and histological
      inflammation were scored on 4-point scales. At 45 min, a positive correlation was
      found between endoscopic and scan gradings in individual colon segments when
      using visual grading and three of the four computer-aided methods (Spearman's rs
      = 0.30-0.64, P < 0.001). Histological grading correlated with visual grading and
      with two of the four computer-aided methods at 45 min (rs = 0.42-0.54, P <
      0.001). At 4 h, all grading methods correlated positively with both endoscopic
      and histological assessment. The correlation coefficients were, in all but one
      instance, highest for the visual grading. As an inter-observer comparison to
      assess agreement between the visual gradings of two nuclear physicians, 14
      additional patients (9 ulcerative colitis, 5 infectious enterocolitis) underwent
      leukocyte scintigraphy. Agreement assessed using kappa statistics was 0.54 at 45
      min (P < 0.001). Separate data concerning the presence/absence of active
      inflammation showed a high kappa value (0.74, P < 0.001). Our results showed that
      a simple scintigraphic scoring system based on assessment using the human eye
      reflects colonic inflammation at least as well as computer-aided grading, and
      that highly correlated results can be achieved between different investigators.

PMID- 7624111
TI  - Pharmacokinetics of 111In-labelled monoclonal antibody ZCE-025 and fragments in
      tumour-bearing mice.
AB  - Radiolabelled anti-tumour antibodies, their fragments and derivatives hold
      promise for imaging and therapeutics in oncology. A better understanding of the
      pharmacokinetics of these entities is therefore important for clinical
      applications and management. In the present study, the in vivo behaviour of
      111Indium-labelled monoclonal anti-CEA antibody ZCE-025 and its F(ab')2 and Fab'
      fragments and a Fab' derivative are compared in the nude mouse-human tumour
      model. The object of the derivative was to improve the tumour uptake of the
      fragment yet reduce its high renal uptake while continuing to achieve desirable
      kinetics in the normal tissues. Uptake of the derivative in the tumour was
      comparable to that of the intact antibody and exceeded that of the underivatized
      fragments. Moreover, uptake in non-target tissues was lower with the derivative
      than with the intact entity. The renal uptake of the derivative was dramatically
      lower than for the fragments. The modelling data strongly suggest that the
      derivatives will be advantageous for clinical use compared with the underivatized
      whole antibodies or their fragments.

PMID- 7624112
TI  - NIOSH publishes respirator final rule.

PMID- 7624114
TI  - What is successful CPR?

PMID- 7624113
TI  - Workplace violence. Threat from within.

PMID- 7624115
TI  - Avoiding heat stress.

PMID- 7624116
TI  - A human temperature-sensitive p53 mutant p53Val-138: modulation of the cell
      cycle, viability and expression of p53-responsive genes.
AB  - A human p53 mutant, p53Val-138 (amino acid 138, Alanine-->Valine), generated by
      in vitro mutagenesis was introduced into Saos-2 human osteosarcoma and Jurkat
      acute T-lymphoblastic leukemia cell lines, both lacking p53 protein expression.
      p53Val-138 caused growth arrest in Saos-2 cell line and apoptosis in Jurkat cell
      line at 32.5 degrees C while it allowed both cell lines to grow continuously at
      37.5 degrees C. p53Val-138 activated expression of p53-responsive genes including
      MDM2, GADD45 and WAF1/CIP1/SD11 in Saos-2 cell line upon the temperature shift
      down from 37.5 degrees C to 32.5 degrees C. Thus, p53Val-138 acted as a
      temperature-sensitive p53 mutant. Taking advantage of these human cell systems,
      we demonstrated that p53-mediated cell cycle arrest occurred in G1 and G2/M
      phases of Saos-2 cell line but not in Jurkat cell line. The induced level of
      WAF1/CIP1/SDI1 mRNA by p53 was extremely lower in Jurkat cell line than that of
      Saos-2 cell line. However, MDM2 mRNA accumulated to the similar levels in these
      two cell lines. These results suggest that a factor(s) other than p53 may be
      involved in differential expression of WAF1/CIP1/SDI1 and MDM2 mRNA.

PMID- 7624117
TI  - Activated RET/PTC oncogene elicits immediate early and delayed response genes in
      PC12 cells.
AB  - The expression of the receptor-like tyrosine kinase RET is associated with
      tumors, tissues or cell lines of neural crest origin. In addition RET products
      (Ret) are involved in determining cell fate during the differentiation of the
      enteric nervous system and during renal organogenesis. However, as yet, no direct
      evidence exists to indicate that the Ret kinase activity might interfere in a
      specific way with cellular differentiation, or proliferation, of a neural crest
      derived cell line. By using two constitutively activated forms of RET (RET/PTC1
      and RET/PTC3) in transient transfection experiments, we have obtained evidence
      that active RET could reprogramme the gene expression pattern in the rat
      pheochromocytoma PC12 cell line. Transcription driven by gene promoters, such as
      NGFI-A and vgf, which belong, respectively, to primary and delayed response genes
      to nerve growth factor (NGF), and by the neuron-specific enolase (NSE) promoter,
      is rapidly induced by the expression of activated RET oncogenes. This induction
      is not elicited in other non neural derived cell types tested. We also
      demonstrate that endogenous ras activity is required for RET induction of these
      neural markers. Finally, in the RET/PTC transfected PC12 cells, NGF is unable to
      induce further their transcription. This suggests that RET/PTC could share an
      intracellular signalling pathway with the NGF-receptor.

PMID- 7624118
TI  - Activated RET oncogene products induce maturation of xenopus oocytes.
AB  - The RET proto-oncogene encodes a transmembrane receptor of the tyrosine kinase
      family, recently found to be the gene responsible for the multiple endocrine
      neoplasia type 2A and 2B syndromes. RET was found specifically activated, by gene
      rearrangement, in human thyroid carcinomas of the papillary subtype. In most
      cases the activation consisted of an in frame fusion of the RET tyrosine-kinase
      domain, at the carboxy-terminus, with heterologous genes at the amino-terminus.
      These chimeric oncogenes are collectively named RET/PTC. Two forms of these gene
      products, RET/PTC1 and RET/PTC3, have been tested for their ability to induce
      meiotic maturation in Xenopus oocytes. Injection of RET/PTC mRNAs into immature
      oocytes induced maturation-promoting-factor (MPF) activation and germinal vesicle
      breakdown (GVBD). The injected oocytes expressed polypeptides recognized by an
      anti-RET gene product antibody as well as by an antiphosphotyrosine antibody,
      indicating activation of the tyrosine-kinase domain. The RET/PTC induced
      maturation was dependent on endogenous ras; in fact, the coinjection of RET/PTC
      mRNA with a neutralizing anti-ras antibody blocked oocytes maturation without
      interfering with the accumulation and tyrosine-phosphorylation of the RET/PTC
      protein.

PMID- 7624119
TI  - Wild type PAX3 protein and the PAX3-FKHR fusion protein of alveolar
      rhabdomyosarcoma contain potent, structurally distinct transcriptional activation
      domains.
AB  - Alveolar rhabdomyosarcoma (ARMS) is characterized cytogenetically by a
      t(2;13)(q35;q14) chromosomal translocation involving two transcription factor
      genes: PAX3 and FKHR. ARMS cells express a PAX3-FKHR fusion protein containing
      the complete N-terminal, DNA-binding domain of PAX3 and the C-terminus of FKHR.
      Recently we demonstrated that PAX3-FKHR is a more potent transcriptional
      activator than PAX3 despite impaired binding to canonical PAX3 binding sites.
      Therefore, we propose that the gene fusion results in switching of PAX3 and FKHR
      transactivation domains with distinct structure, potency or function. To compare
      the PAX3 and putative PAX3-FKHR transactivation domains, we fused C-terminal test
      fragments to the heterologous GAL4 DNA-binding domain and tested activation of a
      reporter gene co-transfected into four cell types. GAL4-PAX3 and GAL4-PAX3-FKHR
      were found to be potent activators exhibiting different concentration-dependent
      transactivation profiles and distinct structural motifs. Deletion mapping
      demonstrated essential acidic and/or serine/threonine-rich domains in the extreme
      3' ends of their respective coding regions and positive modifying elements in
      adjacent 5' sequences. These data demonstrate that PAX3 and PAX3-FKHR contain
      structurally distinct transcriptional activation domains and suggest that a
      consequent difference in function is important for oncogenesis.

PMID- 7624120
TI  - Discordant regulation of SCL/TAL-1 mRNA and protein during erythroid
      differentiation.
AB  - The SCL/TAL1 gene was originally identified by virtue of its rearrangement and
      transcriptional activation in patients with T cell acute lymphoblastic leukaemia.
      It encodes a helix-loop-helix transcription factor, is not normally expressed in
      T cells, but is expressed in erythroid, mast, megakaryocytic and progenitor
      cells. Over-expression of sense and antisense constructs have implicated SCL as a
      positive regulator of erythroid differentiation. In addition we have previously
      shown that SCL mRNA levels undergo biphasic modulation during induced erythroid
      differentiation of murine erythroleukaemia (MEL) cells with a transient early
      fall followed by a late rise. In this paper we have studied expression of the SCL
      protein during erythroid differentiation and also the molecular basis for the
      raised SCL mRNA levels that accompany erythroid differentiation. We have
      generated an anti-SCL antiserum and used it to demonstrate that an early
      transient fall in SCL protein does not occur during induced differentiation of
      MEL cells. Furthermore SCL protein levels underwent a late fall in three
      different models of erythroid differentiation and in two models of myeloid
      differentiation. The fall in SCL protein levels during induced erythroid
      differentiation contrasted with the concomitant marked rise in SCL mRNA levels.
      These observations have significant implications for the mechanism by which SCL
      may regulate erythropoiesis. In addition we have demonstrated that the stability
      of SCL mRNA was only marginally enhanced during erythroid differentiation of MEL
      cells, whereas the activity of a luciferase reporter construct driven by the SCL
      promoter was increased 11- to 17-fold. Up-regulation of transcription therefore
      accounted for most of the increase in SCL mRNA levels during erythroid
      differentiation.

PMID- 7624121
TI  - Mutant p53 is not fully dominant over endogenous wild type p53 in a colorectal
      adenoma cell line as demonstrated by induction of MDM2 protein and retention of a
      p53 dependent G1 arrest after gamma irradiation.
AB  - To determine whether a single mutational event in one p53 gene is sufficient to
      confer a significant growth advantage on a colonic epithelial cell, the 143(Ala)
      p53 mutation was previously expressed in the human colonic adenoma derived cell
      line AA/C1 (which is wild type for p53) and shown to have no effect on it's in
      vitro or in vivo growth characteristics. In this investigation, by expressing the
      175(His), 248(Trp) or 273(His) mutations in the same AA/C1 cell line, we have
      shown that this failure to affect the growth of the cells was not mutant
      specific. We have also demonstrated, using induction of MDM2 protein and the
      ability of the cells to undergo a p53 dependent G1 arrest, that the 143(Ala),
      175(His) or 248(Trp) transfected cells retain functional endogenous wild type p53
      activity, and suggest that these p53 mutations would not have a fully dominant
      negative mode of action in vivo. In contrast, one of the two AA/C1 cell lines
      transfected with the 273(His) mutation did fail to cell cycle arrest after gamma
      irradiation, indicating that this mutation can act as a dominant negative.
      However even loss of wild type p53 function in this cell line was insufficient to
      directly effect the growth rate of the AA/C1 cells, suggesting that acquisition
      of the 273(His) mutation may contribute to malignant progression through genomic
      instability (by inhibiting the G1 arrest) and that other mutations are required
      before outgrowth of the cell population containing the p53 mutation.

PMID- 7624122
TI  - Differences in sensitivity to induction of apoptosis among rat fibroblast cells
      transformed by HTLV-I tax gene or cellular nuclear oncogenes.
AB  - The tax gene of human T lymphotropic virus type I has been implicated in the
      genesis of adult T cell leukemia (ATL). It has been reported that expression of
      tax induces neoplastic transformation in the rat fibroblast cell line Rat-1, and
      that co-expression with the ras gene can transform rat embryo fibroblasts.
      Possible activation of cellular oncogenes including c-myc and c-fos by tax has
      been implicated in these tax functions. In this study, comparative analysis of
      biological properties of tax and cellular nuclear oncogenes c-myc and c-fos was
      performed in Rat-1 cells. While all three oncogenes could transform Rat-1 cells,
      significant differences in the sensitivity to induction of apoptosis were
      observed between cells transformed with each oncogene. Induction of apoptosis by
      serum starvation was observed in tax-transfected Rat-1 cells but to a lesser
      extent than that in those transfected with c-myc or c-fos. In contrast, exposure
      to a DNA-damaging agent, etoposide, resulted in enhanced apoptotic death only in
      c-myc-transfected Rat-1 cells. Our findings indicate that the pathways for
      apoptosis induction may not be identical among these three oncogenes, and that
      the relatively low apoptosis-inducing activity and sufficient transforming
      capacity of tax might be associated with transformation of T cells and the low
      susceptibility of the transformed T cells (ATL cells) to chemotherapeutic agents.

PMID- 7624123
TI  - Cell cycle dependent effects of u.v.-radiation on p53 expression and
      retinoblastoma protein phosphorylation.
AB  - Control of fate of cells encountered with DNA damaging agents is pivotal for
      normal cellular homeostasis. DNA damage leads in many cases to growth arrest of
      the cells ensuring sufficient time for damage repair. Growth arrest can be
      mediated by p53 tumor suppressor protein and loss of its function leads to
      inability of the cells to both growth arrest and undergo apoptosis. We show here
      that followed by genotoxic stress, the retinoblastoma gene product, pRB, is
      associated with growth arrest of cells in a p53 independent manner. In u.v.
      treated human and mouse fibroblasts, pRB is rapidly dephosphorylated. pRB
      dephosphorylation occurs concomitant with growth arrest of cells including cells
      with p53 mutations (SW 480 colon carcinoma cells), cells expressing SV40 T
      antigen and rat-transformed cells (T-24 bladder carcinoma cells) unresponsive in
      regard to p53 stimulation. Furthermore, flow cytometry analysis of u.v.-radiated
      synchronized G1 cells indicates that the cells transiently arrest in G1 for 10-12
      h with pRB dominating in its underphosphorylated form, whereas p53 accumulation
      occurs only after the cells have entered into S-phase. In addition, u.v.
      radiation of late S- and G2/M-phase cells leads to p53 accumulation and cell
      cycle arrest. The results indicate that p53 accumulation upon u.v.-radiation
      occurs during DNA replication and is thus not involved in G1 arrest. We suggest
      that the events that lead to pRB dephosphorylation upon u.v.-radiation provide
      the cell an efficient G1 arrest which occurs prior and independently of p53.

PMID- 7624124
TI  - Suppression of RAS and MOS transformation by radicicol.
AB  - Activated versions of ras and mos oncogenes subvert the signal transduction
      pathway by mimicking transducers at the plasma membrane and cytosol respectively.
      Radicicol (UCS1006), an antifungal antibiotic, had the ability to suppress
      transformation by ras and mos oncogenes in a rapid, reversible and dose-dependent
      manner. UCS1006 inhibited MAP kinase activity (both ERK1 and ERK2) in
      untransformed as well as ras and mos transformed cells. However, ERK2 but not
      ERK1 activity was constitutively elevated in ras and mos transformed cells used
      in this study. In addition, a 62 kDa (kilodalton) phosphoprotein was identified
      whose tyrosine phosphorylation was inhibited by UCS1006, in both ras and mos
      transformed cells. This 62 kDa phosphoprotein, which was found to be heavily
      phosphorylated on tyrosine residues only in the ras and mos transformed cells but
      not in untransformed NIH3T3 cells, was identical to the previously described GAP
      associated tyrosine phosphoprotein, p62, that is the major target for
      phosphorylation in cells transformed by tyrosine kinase oncogenes. These results
      suggest that agents such as radicicol can suppress transformation by diverse
      oncogenes such as src, ras and mos at least in part by inhibiting the function of
      key signal transduction intermediates such as MAP kinase and GAP-associated p62.

PMID- 7624125
TI  - Evidence that c-myc mediated apoptosis does not require wild-type p53 during
      lymphomagenesis.
AB  - Deregulation of c-myc, frequently implicated in oncogenesis, is associated with
      increased cell proliferation and also cell death. Similarly, the p53 tumor
      suppressor gene commonly mutated in human tumors, is known to induce apoptosis or
      cell cycle arrest in its wild-type conformation. Genetically altered mice
      simultaneously overexpressing c-myc and possessing a disrupted p53 gene were used
      to investigate whether c-myc mediated apoptosis requires wild-type p53. The
      accelerated development of malignant lymphomas in these mice was found to be a
      consequence of enhanced proliferation and not reduced apoptosis resulting from
      the synergistic effect of c-myc overexpression and p53 inactivation.

PMID- 7624126
TI  - The MMTV/c-myc transgene and p53 null alleles collaborate to induce T-cell
      lymphomas, but not mammary carcinomas in transgenic mice.
AB  - A number of properties of the cancer-related genes c-myc and p53 suggest that
      they might collaborate to induce tumorigenesis. To test this notion, we produced
      doubly heterozygotic mice bearing disrupted p53 alleles and a fusion transgene
      consisting of the mouse mammary tumor virus (MMTV) LTR and the oncogene c-myc.
      Mice bearing both the MMT/c-myc transgene and a single p53- allele develop very
      aggressive pre-T- and T-cell lymphomas with a significantly shorter latency than
      mice carrying either the p53- allele or the c-myc transgene alone. Moreover,
      every lymphoma occurring in these animals has lost or suffers an inactivation of
      its wild type p53 allele indicating that loss of p53 activity is necessary for
      this c-myc-accelerated lymphomagenesis. Nonetheless, p53 inactivation and
      expression of the MMTV/c-myc transgene are not sufficient for lymphoid
      transformation. Tumors that arise in homozygous p53- mice carrying the c-myc
      transgene are monoclonal, suggesting that at least one additional event is
      necessary for their transformation. Moreover, since mice bearing only the MMTV/c
      myc transgene predominantly develop mammary carcinomas, it was surprising that
      the p53- allele failed to accelerate the incidence of mammary carcinomas.
      Further, in contrast to the lymphomas, only one in four mammary tumors that arose
      in the double heterozygotic mice had lost its wild type p53 allele. Apparently
      cell context influences the ability of c-myc and p53- to cooperate in inducing
      oncogenesis.

PMID- 7624127
TI  - The Evi-1 zinc finger myeloid transforming protein binds to genomic fragments
      containing (GATA)n sequences.
AB  - The EVI1 gene is activated by chromosomal translocations and inversions in
      approximately 5% of human acute myeloid leukemia (AML) and by retroviral
      insertion in approximately 20% of murine myeloid leukemias. EVI1 encodes a
      nuclear DNA-binding protein having 10 zinc finger motifs in two noncontiguous
      domains consisting of an amino-terminal domain of seven fingers and a carboxyl
      domain containing three fingers. To evaluate the sequence specificity of Evi-1
      binding and potentially identify genomic targets, whole-genome PCR was utilized
      to isolate multiple Sau3A fragments which specifically bind to the amino-terminal
      zinc finger domain. The majority of these clones represented single copy
      sequences and virtually all contained variable numbers of repeats of the GATA
      motif, the target sequence for the erythroid-specific transcription factor GATA
      1. GST/Evi-1 fusion proteins containing the amino-terminal domain of zinc fingers
      bound the GATA motif in these clones as well as to those present in the human
      gamma-globin promoter, similar to the binding of purified GATA-1 protein. By
      obtaining corresponding large genomic clones for eight of these fragments,
      transcription units were found associated with two. One corresponded to the
      glyceraldehyde-3-phosphate dehydrogenase gene and its expression was not affected
      by Evi-1. The second is a novel gene whose expression is repressed in murine
      myeloid cell lines that express Evi-1.

PMID- 7624128
TI  - Molecular controls of growth arrest and apoptosis: p53-dependent and independent
      pathways.
AB  - Cell homeostasis is regulated by a balance between proliferation, growth arrest
      and programmed cell death (apoptosis). Until recently, studies on oncogenesis
      have focused on the regulation of cell proliferation. The recognition that
      negative growth control, including growth arrest and programmed cell death, must
      be understood to comprehend how appropriate cell numbers are maintained and how
      alterations in any part of the equation can contribute to malignancy has led to a
      burst of work in this field. This review focuses on what has been learned about
      distinct settings of negative growth control, analyzing p53-dependent and
      independent pathways of growth arrest and apoptosis either coupled or uncoupled
      from differentiation, with an emphasis on the use of hematopoietic cells. The
      importance of understanding the molecular biology of apoptotic and growth arrest
      pathways in cancer therapy, and future directions to study negative growth
      control are addressed as well.

PMID- 7624129
TI  - A new type of p16INK4/MTS1 gene transcript expressed in B-cell malignancies.
AB  - Chromosome band 9p21-22 is frequently altered by nonrandom abnormalities, mainly
      deletions, in hemopoietic malignancies of the lymphoid lineage. We have analysed
      a translocation t(9;14)(p21-p22;q11) in a B-cell type acute lymphoblastic
      leukemia. Location of the 14q11 breakpoint within the TCR-alpha/delta locus
      allowed the isolation of a fusion transcript composed of a 3' segment containing
      part of the constant region of the TCR-alpha gene and a 5' segment from
      chromosome 9, designated 0.18. This 0.18 segment was also part of cDNAs isolated
      from two tumoral B-cell lines (RPMI-8226, Raji). In both cases, 0.18 was
      juxtaposed 5' to a sequence corresponding to exons 2 and 3 of the p16INK4/MTS1
      gene which is located on band 9p21-22. Unexpectedly, none of the two ATG codons
      found in 0.18 was in phase with that of the exons 2 and 3 of p16INK4/MTS1.
      Furthermore, in vitro translation product of a RPMI-8226 cDNA clone generated a
      product that was not immunoprecipitated by antibodies specific of the C-terminal
      end of the p16INK4/MTS1 protein. Evidence for similar transcripts in non tumoral
      lymphoid B cells (unstimulated peripheral blood lymphocytes (PBL) and
      lymphoblastoid cell lines) were obtained by using amplimers representative of the
      0.18 segment and the p16INK4/MTS1 exon 2. Altogether, these data are consistent
      with the existence of a new type of p16INK4/MTS1 transcript whose significance is
      discussed.

PMID- 7624130
TI  - Translocation of activated Rho from the cytoplasm to membrane ruffling area, cell
      cell adhesion sites and cleavage furrows.
AB  - Rho small GTP-binding protein regulates various cell functions, such as formation
      of stress fibers and focal adhesions, cell motility, membrane ruffling,
      cytokinesis and smooth muscle contraction in mammalian cells and bud formation in
      the yeast Saccharomyces cerevisiae. As to the functioning sites of Rho in
      Saccharomyces cerevisiae, we have recently shown that RHO1 protein, a homologue
      of mammalian RhoA, is concentrated to the growth region of the cells where
      cortical actin patches are clustered. However, in mammalian cells, the
      functioning sites of Rho have not yet been studied. In the present study, MDCK
      cell lines stably expressing myc-tagged RhoA (myc-RhoA) were prepared and
      localization of myc-RhoA was first immunohistochemically examined using an anti
      myc antibody. In the resting cells, almost all of myc-RhoA was observed in the
      cytosol. When the cells were stimulated with phorbol ester or hepatocyte growth
      factor, membrane rufflings were induced and myc-RhoA was translocated to the
      membrane ruffling area. Moreover, myc-RhoA was translocated from the cytosol to
      the cell-cell adhesion sites when the cells were transferred from a low to normal
      Ca2+ medium. RhoA was also concentrated to the cleavage furrows during
      cytokinesis in Swiss 3T3 cells. Translocation of myc-RhoA to the membrane
      ruffling area was inhibited by prior microinjection into the cells of Rho GDI, a
      negative regulator of Rho which inhibits activation of Rho, or of C3, an
      exoenzyme of Clostridium botulinum which ADP-ribosylates Rho and inhibits its
      functions, indicating that both activation and functioning of Rho are essential
      for the translocation of Rho. The ERM (Ezrin, Radixin, Moesin) family members
      were colocalized with RhoA at all of these sites. However, RhoA was not
      apparently observed at the focal adhesion plaque where vinculin was localized.
      These results suggest that at least one of the functioning sites of Rho is the
      ERM family-controlled actin filament/plasma membrane association sites.

PMID- 7624131
TI  - Altered phosphorylation and oligomerization of p53 in adenovirus type 12
      transformed cells.
AB  - Loss of function of the tumor-suppressor protein p53 is, in general, either
      caused by mutation, inducing a conformational change, or by binding to
      inactivating cellular (e.g. MDM2) or viral (e.g. SV40 large T) proteins. In
      adenovirus type 12 (Ad12)-transformed cells, p53 is stabilized without detectable
      binding to the Ad12 E1B/54 kDa protein and still present in a wild-type
      conformation but contains a mutant-like activity in cellular transformation. In
      this study we examined whether the changed characteristics of p53 in Ad12
      transformed cells are correlated with changes in phosphorylation or complex
      formation of the protein. By making tryptic phosphopeptide maps we found a
      significant increase in the phosphorylation of the N-terminus of p53.
      Furthermore, expression of E1A was found to be essential for the altered
      phosphorylation, while expression of only Ad12 E1B/54 kDa is sufficient to
      increase the protein half-life. Additionally, we observed p53 to be present in
      increased molecular weight complexes in Ad12-transformed cells. We conclude that
      both the phosphorylation and oligomerization of p53 is changed as a result of
      Ad12 transformation.

PMID- 7624132
TI  - In vitro growth of factor-dependent multipotential hematopoietic cells is induced
      by the nuclear oncoprotein v-Ski.
AB  - Understanding how self renewal, commitment and differentiation are regulated in
      normal, multipotent hematopoietic progenitors is important for our understanding
      of underlying mechanisms involved in leukemogenesis. In addition, knowledge of
      progenitor cell biology is critical if these cells are to be used for gene
      therapy. In this communication, we demonstrate that the oncogenic transcription
      factor v-Ski, together with the ligand activated receptor tyrosine kinase c-Kit,
      induces the continuous in vitro self renewal of primary avian multipotent
      progenitors. These cells have an in vitro life span of > 100 generations. In
      addition they spontaneously differentiate into cells of the erythroid, monocytic
      and granulocytic lineages. If clonal strains of these multipotent progenitors are
      exposed to specific mixtures of growth factors and hormones, they develop into
      committed cells of either the erythroid or myeloid lineages. These committed
      cells underwent efficient terminal differentiation when they were treated with
      the relevant lineage-specific growth/differentiation factors, but underwent
      apoptosis when exposed to the incorrect factors for the respective lineage. While
      the committed cells coexpress marker proteins from different lineages, expression
      of the 'wrong' lineage marker is repressed during terminal differentiation. Our
      results indicate that a combination of v-Ski and activated c-Kit induces long
      term self renewal in primary multipotent progenitors, which can be induced to
      commit and differentiate along specific lineages under different, defined
      conditions. Our data also suggest that growth factors and steroid hormones
      control terminal differentiation by a combined induction of commitment, growth
      and apoptosis, a process likely to be affected in stem cell leukemias.

PMID- 7624133
TI  - Identification of the Tax interaction region of serum response factor that
      mediates the aberrant induction of immediate early genes through CArG boxes by
      HTLV-I Tax.
AB  - Tax of human T-cell leukemia virus type I (HTLV-I) activates transcription at a
      CArG box of various immediate early genes such as the proto-oncogene c-fos. To do
      this, Tax does not directly bind to the CArG box, but instead binds to the CArG
      binding factor SRF. In this study, we investigated the domain of SRF required for
      the activation by Tax and studied the role of this domain on transcriptional
      regulation at the CArG box. Using a fusion protein of SRF with a yeast
      transcription factor GAL4, the 14 amino acid (aa) portion (aa 422-435) of SRF was
      identified as the domain required for Tax activation [Tax-responsive region of
      SRF (TRRS)]. By means of a two hybrid system, we showed that TRRS was essential
      for the interaction of SRF with Tax in vivo. The over-expression of SRF with a
      deletion of TRRS inhibited the Tax activation at the CArG box. Thus, TRRS is the
      domain of SRF that is essential for Tax activation at the CArG box. Unlike to Tax
      activation, TRRS was not required for TPA (12-o-tetradecanoylphobol-13-acetate)
      induction at the CArG box, but a TRRS deletion enhanced the basal activity at the
      CArG box both under serum-starved and TPA-stimulated conditions. These results
      suggest that TRRS negatively regulates the transcriptional activation function of
      SRF, and consequently contributes to the low basal activity at the CArG box
      before TPA induction.

PMID- 7624134
TI  - Cdk2 kinase phosphorylates serine 315 of human p53 in vitro.
AB  - DNA damage increases p53 protein levels and activates transcription of the p21
      gene. The p21 protein binds to and inhibits cdk2 kinase, causing G1 arrest. Here,
      we have investigated if a p53 fusion protein is a substrate for cdk2 kinase in
      vitro. Cdk2 kinase was immunoprecipitated from NIH3T3 cells and allowed to
      phosphorylate a human p53-GST (glutathione-s-transferase) fusion protein. Cdk2
      and cyclin E-cdk2 efficiently phosphorylated both wild-type (wt) and mutant p53
      GST. Cdk2 immunoprecipitated from cells in Go and early G1 exhibited minimal p53
      kinase activity, whereas cells in S-phase displayed high levels of p53 kinase
      activity. If NIH3T3 cells were X-ray irradiated to induce DNA damage, cdk2 p53
      kinase activity was rapidly inhibited within 1 h, but had recovered by 4 h post
      irradiation. Mutation of serine 315 of p53 to alanine (p53-S315A) abolished
      phosphorylation by cdk2 kinase. However, wtp53 and p53-S315A were equally
      effective at activating transcription when cotransfected with a p53 reporter
      construct. The results demonstrate that ser 315 of p53 is phosphorylated by cdk2
      in vitro. However, ser 315 of wtp53 is not required for transcriptional activity
      in vivo, suggesting that cdk2 phosphorylation of p53 may be involved in
      regulating other cellular functions of wtp53.

PMID- 7624135
TI  - Germ-line Tsc2 mutation in a dominantly inherited cancer model defines a novel
      family of rat intracisternal-A particle elements.
AB  - A spontaneous hereditary cancer syndrome in the Eker rat serves as a useful model
      for studying tissue-specific tumorigenesis. The genetic basis of this germline
      mutation was found to involve the tuberous sclerosis 2 (Tsc2) gene. In this
      study, we have identified and characterized a full-length rat intracisternal A
      particle (IAP) element that has undergone an intronic transposition as the
      mechanism of inactivating the Tsc2 gene. The insertion of this 6253 basepair
      element disrupted the transcription of the gene to give rise to multiple abnormal
      mRNA. Genomic organization of this novel IAP element is similar to a typical
      retroviral structure including the gag, pol and env domains with flanking LTRs.
      This Eker rat associated (ERA) IAP sequence was found to contain multiple
      termination codons rendering it non-functional with respect to its endogenous
      genes. The element is conserved among different rat strains and the distribution
      of the estimated approximately 580 copies throughout the rat genome would support
      their random integration. The net effect of the mutation causes the expression of
      abnormal predicted proteins devoid of the rap1GAP-like catalytic domain that lies
      3' to the insertion. These results provide evidence that cancer predisposition
      can be the direct consequence of germ-like insertional mutation by
      retrotransposition targeting a tumor suppressor gene.

PMID- 7624136
TI  - Subcellular localization of the APC protein: immunoelectron microscopic study of
      the association of the APC protein with catenin.
AB  - Mutations in the APC gene are linked to the development of sporadic colorectal
      tumors as well as to familial adenomatous polyposis. Recently, the APC protein
      was reported to associated with catenins, proteins that bind to the cell adhesion
      molecule E-cadherin. In the present study, we examined the distribution and
      localization of the APC protein and alpha -catenin in the normal mouse intestine
      by light and immunoelectron microscopy using specific antibodies. The APC protein
      was found to be localized in microvilli and in the apical and lateral cytoplasm
      of the epithelial cells, whereas alpha-catenin was detected only in the lateral
      cytoplasm. Double-labeling immunoelectron microscopy showed colocalization of the
      APC protein with alpha-catenin in the lateral cytoplasm, especially along the
      lateral plasma membrane, although a certain portion of the APC protein in this
      region was distributed independently of alpha-catenin. These results suggest that
      a portion of the APC protein localized in the lateral cytoplasm of intestinal
      epithelial cells functions in cooperation with catenins, whereas the APC protein
      in microvilli and in the apical cytoplasm has other functions independent of
      catenins.

PMID- 7624137
TI  - Conserved kappa B element located downstream of the tumor necrosis factor alpha
      gene: distinct NF-kappa B binding pattern and enhancer activity in LPS activated
      murine macrophages.
AB  - Transcriptional activation of various genes by lipopolysaccharide (LPS) is known
      to be mediated, at least in part, by the NF-kappa B/Rel family of transcription
      factors. We have identified a novel kappa B element located immediately
      downstream of the TNF-alpha gene that is conserved together with its flanking
      sequences across species lines and can act as an LPS-responsive enhancer for
      reporter gene constructs driven by the minimal TNF promoter. In extracts from
      activated murine macrophages and macrophage cell lines this element binds several
      non-canonical NF-kappa B/Rel complexes, in addition to p50 (NFKB1) homodimer and
      p50-p65 (NKFB1-RelA) heterodimer. Combination of high-resolution electrophoretic
      mobility shift assays (EMSA) with monospecific antibodies and u.v.-cross-linking
      indicates that the prominent slow migrating complex III contain p65 homodimer and
      c-Rel. The appearance of complex III in EMSA parallels the translocation of p65
      and c-Rel into the nucleus and occurs shortly after LPS induction. Transfection
      experiments with reporter constructs driven by this kappa B element indicate
      strong inducibility by LPS and p65, moderate inducibility by c-Rel and repression
      by p50. Functional activity of sandwich TNF-CAT-TNF constructs further suggests
      that LPS-inducible transcriptional activation of the TNF gene in murine
      macrophages may be partly mediated by a downstream enhancer.

PMID- 7624138
TI  - Cell cycle control in mammalian cells: role of cyclins, cyclin dependent kinases
      (CDKs), growth suppressor genes and cyclin-dependent kinase inhibitors (CKIs).
AB  - All eukaryotic cells possess similar mechanisms to regulate the progression of
      the cell cycle. However, higher eukaryotes have evolved to respond to a large
      array of positive and negative signals with an intracellular or extracellular
      origin. These signals are eventually integrated by a conserved protein engine
      consisting of holoenzymes with kinase activity, which trigger crucial transitions
      during the cell cycle. In this review, the mechanisms by which the mammalian cell
      cycle engine integrates intracellular and extracellular signals of different
      nature are discussed.

PMID- 7624139
TI  - Expression, promoter usage and parental imprinting status of insulin-like growth
      factor II (IGF2) in human hepatoblastoma: uncoupling of IGF2 and H19 imprinting.
AB  - We have studied the promoter utilization and parental imprinting status of human
      IGF2 in three genetically informative hepatoblastomas from patients ranging in
      age from 9 months to 3 years. In all three cases, there is a downregulation of
      promoter P1 in the tumor tissues while the P2 and P3 promoters are upregulated
      compared to the normal liver. One of three patients displayed loss of imprinting
      (LOI) of IGF2 in the tumor tissue. We also investigated the expression of the H19
      gene in all three cases and the methylation pattern in H19 from the patient with
      LOI of IGF2. The expression of H19 was greatly reduced in all tumors. Monoallelic
      H19 expression however, was retained even in the case which showed LOI of IGF2.
      Unlike the situation in Wilms' tumor, no differences in the methylation pattern
      between the normal liver and tumor tissues were observed in the H19 promoter or
      3' region, using HpII analysis. We show here, that in contrast to the situation
      in Wilms' tumor, H19 expression is not a prerequisite for maintaining a
      monoallelic IGF2 expression.

PMID- 7624140
TI  - Suppression of v-Src transformation in primary rat embryo fibroblasts.
AB  - To understand the mechanism for resistance of primary cultures of rat embryo
      fibroblasts (REFs) to oncogene-induced transformation, we studied the
      transforming ability of a recombinant retrovirus, ZSV, containing v-src and neo
      genes in REFs and in the rat cell line F2408. The susceptibility of REFs to p60v
      src transformation was markedly reduced when compared with that of F2408 cells,
      despite high levels of expression of functional p60v-src tyrosine kinase in the
      two systems. In hybrid cells obtained by somatic cell fusion between F2408 cells
      transformed by v-src and uninfected REFs, the transformed phenotype was
      suppressed despite persistent expression of p60v-src tyrosine kinase. On the
      other hand, hybrid cells between v-src transformed F2408 cells and uninfected
      F2408 cells retained the transformed phenotypes. These results indicate that
      primary cells possess an intracellular function(s) that cause suppression of the
      transformed phenotype induced by the v-src gene. In ZSV-infected REFs, tyrosine
      phosphorylation of cellular proteins, including p125 focal adhesion kinase, p70
      paxillin and p130 was similar to that in the ZSV-infected F2408 cells, indicating
      that tyrosine phosphorylation of these proteins is not sufficient for the
      expression of transformed phenotype. On the other hand, cellular fibronectin and
      one of integrin receptors were downregulated in the ZSV-transformed F2408 cells
      but not in ZSV-infected REFs, suggesting that fibronectin and/or its receptor
      might play a role in suppressing v-src transformation in primary rat cells.

PMID- 7624141
TI  - Induction of neurite outgrowth by MAP kinase in PC12 cells.
AB  - Treatment of PC12 cells with nerve growth factor (NGF) results in neural
      differentiation of the cells, inducing neurite outgrowth. Ras protein has been
      shown to play an essential role in this process. To examine whether or not the
      MAP kinase (MAPK) cascade mediates the NGF- and Ras-induced neural
      differentiation process, we injected PC12 cells with constitutive active forms of
      each components of the MAPK cascade. When a moderately active mutant of Xenopus
      MAPK kinase (S222E-MAPKK) in which Ser 222 was changed into glutamic acid was
      injected, the neurite outgrowth of PC12 cells occurred to some extent. Injection
      of an N-terminal truncated STE11 protein (delta N-STE11), a constitutively active
      form of STE11 which is a yeast MAPKK kinase, induced neurite outgrowth in PC12
      cells. Furthermore, injection of thiophosphorylated MAPK, but not purified active
      MAPK, into PC12 cells resulted in neurite outgrowth. Thiophosphorylated MAPK was
      resistant to protein phosphatase 2A treatment, while purified active MAPK was
      inactivated by this treatment. All these results have suggested that sustained
      activation of MAPK is sufficient for PC12 cell differentiation. In accord with
      this, the delta N-STE11- or S222E- MAPKK-induced neurite outgrowth was inhibited
      by coinjection of CL-100 protein, a dual-specificity phosphatase that is capable
      of inactivating MAPK.

PMID- 7624142
TI  - Effects of cell cycle, wild-type p53 and DNA damage on p21CIP1/Waf1 expression in
      human breast epithelial cells.
AB  - In this study we examine the relationship between p21CIP1/Waf1 (CIP1), a 21 kDa
      protein that binds to and modulates the activity of several cyclin dependent
      kinases and expression of wild-type (WT) p53 in human breast epithelial cells.
      Basal CIP1 protein, but not CIP1 mRNA levels correlated well with expression of
      WT p53 in human breast epithelial cells. To obtain more direct evidence that WT
      p53 regulated the level of CIP1 protein, the Human Papilloma Virus (HPV) E6
      protein was introduced into immortalized 184B5 breast cells. Residual WT p53
      levels correlated well with CIP1 protein but not CIP1 mRNA levels in isolated
      clones of transfected cells. CIP1 protein was increased at early times after
      growth factor arrested cells were stimulated to proliferate. The rise in CIP1
      protein was due to a concomitant increase in CIP1 mRNA levels in MCF10, but not
      in normal mammary epithelial cells. DNA damage induced by ionizing radiation
      resulted in a transient increase in WT p53 levels but a prolonged induction of
      CIP1 protein. The sustained increase in CIP1 protein 24 h after radiation could
      not be attributed to a concomitant increase in CIP1 mRNA levels. Although the
      half-life of the CIP1 protein was not altered following irradiation, a fourfold
      increase in the amount of radioactivity incorporated into CIP1 protein was
      detected. When considered together these data suggest that wild-type p53 affects
      CIP1 protein accumulation at a posttranscriptional level in human breast
      epithelial cells under different physiologic and stress conditions.

PMID- 7624143
TI  - p53 wild-type and p53 nullizygous Big Blue transgenic mice have similar
      frequencies and patterns of observed mutation in liver, spleen and brain.
AB  - Transgenic mouse mutation detection systems offer a powerful tool for analysis of
      spontaneous and induced mutations in vivo. Mice doubly transgenic for a null
      mutation of the p53 tumor suppressor gene and a lambda shuttle vector harboring
      the lacI gene were utilized to examine the rate and pattern of spontaneous
      somatic mutation of the lacI transgene in vivo. Three somatic tissues were
      examined: liver, spleen and brain. At 6 weeks of age, three p53 wild type (+/+)
      and three p53 nullizygous (-/-), lacI (+/-) male mice were analysed. The mutation
      frequencies in the two genotypes were similar. The mutant frequencies for wild
      type (+/+) and nullizygous (-/-) p53 genotypes were, respectively, 4.2 x 10(-5)
      and 3.6 x 10(-5) in the liver, 4.3 x 10(-5) and 3.4 x 10(-5) in the spleen and
      2.8 x 10(-5-) and 3.0 x 10(-5) in the brain. When the data from the three tissues
      were combined, the mutant frequency was 3.7 x 10(-5) for the (+/+) genotype and
      3.3 x 10(-5) for the (-/-) genotype. By sequencing both strands in the DNA
      binding region of the lacI gene, 91 mutations were found. When recurrent
      mutations in the same mouse were excluded, a total of 67 definitely independent
      mutations were found. No statistically significant differences were found in the
      mutational spectra between the two genotypes when the three tissues were analysed
      individually or combined (P = 0.58). These findings suggest a need to reconsider
      the general form of hypothesis that the p53 gene serves as the 'guardian of the
      genome'.

PMID- 7624144
TI  - Cloning and developmental expression of Nsk2, a novel receptor tyrosine kinase
      implicated in skeletal myogenesis.
AB  - The protein superfamily of transmembrane receptor tyrosine kinases (RTKs) are
      essential components of intercellular signalling pathways necessary for normal
      cellular regulation. We report the cloning and developmental expression pattern
      of Nsk2, a novel, structurally distinct mammalian RTK characterised by a putative
      extracellular region bearing four immunoglobulin-like domains. The Nsk2 locus was
      mapped to the distal region of mouse chromosome 13 and was found to be expressed
      preferentially in skeletal muscle amongst adult mouse tissues. Moreover,
      increased steady-state levels of Nsk2 transcripts were apparent on terminal
      differentiation of committed skeletal myoblast cell lines in vitro and multiple
      isoforms of the Nsk2 RTK were identified in skeletal myotube cultures. RNA in
      situ hybridisation studies of mouse embryos confirmed skeletal myogenesis to be a
      major site of Nsk2 expression during normal embryogenesis, and identified other
      likely sites of Nsk2 function in ganglia of the developing peripheral nervous
      system and various embryonic epithelia, including those of kidney, lung and gut,
      during fetal development. Taken together, our data suggest normal functions for
      Nsk2 RTKs in distinctive aspects of skeletal muscle development, neurogenesis and
      mesenchymal-epithelial interactions during organ formation.

PMID- 7624145
TI  - DNA binding specificities of Spi-1/PU.1 and Spi-B transcription factors and
      identification of a Spi-1/Spi-B binding site in the c-fes/c-fps promoter.
AB  - Spi-1/PU.1 and Spi-B encode hematopoietic-specific transcription factors that are
      the most distantly related members of the Ets family. The Ets proteins share a
      conserved 85 amino acids DNA binding domain, the Ets domain and recognize various
      DNA target sites around a common core 5'-GGAA/T-3'. The DNA binding specificities
      of Spi-1 and Spi-B were investigated by using the method of polymerase chain
      reaction (PCR)-mediated random site selection. The deduced Spi-1 and Spi-B
      consensus binding sites are very similar suggesting that the functional
      activities of Spi-1 and Spi-B cannot be distinguished on the basis of their DNA
      binding specificities. We identified a putative Spi-1/Spi-B binding site in the
      promoter region of the c-fes/c-fps protooncogene which encodes a tyrosine kinase
      expressed predominantly in myeloid cells. In vitro translated Spi-1 and Spi-B
      proteins were capable to bind this site similarly and to activate the c-fes
      promoter in HeLa transfected cells. We showed that Spi-1 binds the Spi-1/Spi-B
      binding site of c-fes in HL-60 cells suggesting that Spi-1 may be involved in the
      regulation of c-fes transcription in myeloid cells. Intriguingly, we detected
      only Spi-1 binding to this site in the Raji cell line which express both Spi-1
      and Spi-B proteins. This suggests that Spi-1 and Spi-B exhibit different DNA
      binding activities in vivo although they share similar DNA binding specificities
      in vitro.

PMID- 7624146
TI  - Preferential detection of catalytically inactive c-erbB-2 by antibodies to
      unphosphorylated peptides mimicking receptor tyrosine autophosphorylation sites.
AB  - The c-erbB-2 tyrosine kinase is often overexpressed in human breast cancer, but
      correlations of receptor expression with tumour behaviour have proven elusive in
      patients without metastases at diagnosis. To address the possibility that
      receptor function may be more informative than expression, we previously
      developed function-specific c-erbB-2 antibodies using synthetic tyrosine
      phosphorylated peptide immunogens (Epstein et al., Proc. Natl. Acad. Sci. USA
      1992; 89: 10435-10439). Here the converse approach has been taken to determine
      the functional status of c-erbB-2 receptors detected by antibodies to
      dephosphorylated (dep) autophosphorylation sequences. In contrast to
      antiphosphopeptide (apt) antibodies, dep antibodies to the Tyr1248
      autophosphorylation site exhibited preferential, but not exclusive, binding to
      tyrosine-dephosphorylated c-erbB-2. Consistent with this, catalytically active
      and inactive receptors could not be clearly distinguished by in vitro
      autophosphorylation experiments in which c-erbB-2 was immunoprecipitated using a
      monoclonal Tyr1248 dep antibody. A dep antiserum recognizing autophosphorylation
      sites N-terminal to Tyr1248 exclusively recognized tyrosine-dephosphorylated c
      erbB-2 following antibody preabsorption with homologous phosphopeptides. Although
      indirect, these data are consistent with a model of sequential c-erbB-2
      autophosphorylation in which Tyr1248 is the final residue modified. Moreover,
      since many studies of c-erbB-2 expression have used antibodies to
      dephosphorylated autophosphorylation sites, these results caution against
      automatically equating such receptor immunoreactivity with in vivo function or
      clinical significance.

PMID- 7624147
TI  - Schwann cells from neurofibromin deficient mice exhibit activation of p21ras,
      inhibition of cell proliferation and morphological changes.
AB  - Schwann cells are thought to be abnormal in type 1 neurofibromatosis (NF1) and to
      contribute to the formation of benign and malignant tumors in this disease. To
      test the role of the NF1 gene product neurofibromin as a Ras-GTPase activating
      protein in Schwann cells, and to study the effect of the loss of neurofibromin on
      Schwann cell proliferation, we isolated Schwann cells from mice with targeted
      disruption of NF1. The properties of these neurofibromin deficient cells were
      strikingly similar to those of v-ras expressing rat Schwann cells with normal
      levels of neurofibromin. The similarities included: growth inhibition, noted as a
      decrease in cell division in response to glial growth factor 2 (GGF2) and of
      neuronal contact; morphological changes such as the appearance of elaborated
      processes; and elevated levels of Ras-GTP. Furthermore, Ras-GTP levels in the
      neurofibromin deficient Schwann cells were consistently elevated in response to
      GGF2 treatment. In contrast to these results, introduction of v-ras into a
      Schwannoma cell line (RN22) led to cell transformation. We conclude that
      neurofibromin functions as a major regulator of Ras-GTP in Schwann cells;
      however, mutation in NF1 by itself is unlikely to explain the hyperplasia
      observed in Schwann cell tumors in NF1 disease.

PMID- 7624148
TI  - The basic carboxy-terminal domain of human p53 is dispensable for both
      transcriptional regulation and inhibition of tumor cell growth.
AB  - To investigate the relevance of the C-terminal domains of the human p53 tumor
      suppressor gene to its growth suppressive and transcriptional regulatory
      properties deletion mutants were generated which eliminated 30 (p53 delta 363),
      60 (p53 delta 333) and 87 (p53 delta 306) amino acids from the C-terminus of the
      p53 protein. p53 delta 363 has lost the highly basic tail of the protein
      (residues 360-386). p53 delta 333 and p53 delta 306 lack the oligomerization
      domain (residues 320-360); p53 delta 306 has also lost the major nuclear
      localization signal of p53 (NLSI, residues 316-325). These mutants were assayed
      for transactivation from two p53 consensus binding sites and for transcriptional
      repression of two promoter systems in Calu6 lung cancer cells (p53 null).
      Moreover, their ability to inhibit cell growth in tumor cell lines with a defined
      p53 status was analysed. Deletion of the oligomerization domain correlated with
      significant loss of: (a) transactivation from a genomic sequence; (b)
      transcriptional repression; (c) the ability to inhibit colony formation. An
      intact NLSI was not a prerequisite for transactivation. p53 delta 363 behaved
      similarly to wt p53 in all the assays. We established an inducible expression
      system for p53 delta 363 in a human fibrosarcoma cell line known to be growth
      suppressed by wt p53. The induction of p53 delta 363 expression also inhibited
      cell proliferation albeit to a lesser extent than wt p53. However, p53 delta 363
      could upregulate WAF1/CIP1, GADD45 and MDM2 genes. Thus, the basis tail of p53
      appears not to be required for the biological functions of the protein assayed.

PMID- 7624149
TI  - Frequent deletion of chromosome 19 and a rare rearrangement of 19p13.3 involving
      the insulin receptor gene in human ovarian cancer.
AB  - Human ovarian cancer cells usually have multiple specific chromosomal deletions
      which can be detected by cytogenetic analysis or molecular techniques. Tumour
      suppressor genes might be located in these deleted chromosomal segments. The
      importance of these different loci is usually estimated from the frequency with
      which they are deleted. Here we report a 59% loss of heterozygosity for
      chromosome 19 in the DNA of human invasive epithelial ovarian cancer from a
      series of 37 patients. In all cases informative on both chromosomal arms a
      subchromosomal loss is observed. Analysis of the same tumours for chromosome 17p
      and 11p loss suggests that loss of chromosome 19p/q is less important than 17p
      loss, but more important than 11p loss. The deletion of chromosome 19q seems to
      be associated with distant, hematogeneous metastasis (stage IV). In two patients
      with high grade tumours, the deletion involves a rearrangement of the insulin
      receptor locus (19p13.3). This suggests that some of the previously described
      frequent cytogenetic 19p+ markers and 19p13.3 breaks observed in high grade
      ovarian cancers, might actually occur in the insulin receptor gene.

PMID- 7624150
TI  - Allelic loss at 7q31.1 in human primary ovarian carcinomas suggests the existence
      of a tumor suppressor gene.
AB  - We studied loss of heterozygosity (LOH) in chromosome 7q in order to determine
      the location of a putative tumor suppressor gene (TSG) in human epithelial
      ovarian carcinomas. Samples were obtained from 26 primary ovarian carcinomas at
      the time of staging laparotomy. Paired normal and tumoral DNAs were used as
      templates for polymerase chain reaction amplification of a set of 14 (C-A)n
      microsatellite repeats on 7q21-qter. All the cases studied presented LOH at one
      or more loci on 7q. Seventy-three percent LOH (in 14 of 19 informative cases)
      were detected in D7S522 at 7q31.1. The percentages of LOH were normally
      distributed around microsatellite D7S522 determining a smallest common deleted
      region of 1 cM. The high incidence of LOH in primary ovarian carcinomas suggests
      that a TSG relevant to the development of ovarian cancers is present at 7q31.1,
      confirming our previous functional evidence for a TSG in this region.

PMID- 7624151
TI  - Heterodimerization of c-Jun with ATF-2 and c-Fos is required for positive and
      negative regulation of the human urokinase enhancer.
AB  - Dimerization plays a pivotal role in modulating the activity of the c-Jun proto
      oncogene product. Heterodimerization with activating transcription factor-2 (ATF
      2) alters the DNA-binding specificity of c-Jun, allowing its targeting to several
      cAMP responsive element (CRE)-related sequences, which control a subset of AP-1
      responsive genes. Here we show that a c-Jun/ATF-2 heterodimer binds to the AP-1
      site (uPA 5'-TRE) essential for the activity of the human urokinase enhancer,
      conferring on this element several distinctive regulatory properties. The c
      Jun/ATF-2 heterodimer was identified by binding competition assays, u.v. cross
      linking, and monospecific antibodies. In vitro binding studies revealed that the
      uPA 5'-TRE sequence is recognized by the cyclic AMP-unresponsive ATF-2 factor,
      but not by the cyclic AMP-inducible CREB. In addition, in vivo studies suggest
      that ATF-2 can mediate, at the same time, the activation of the c-Jun/ATF-2 site
      and the repression of the canonical collagenase AP-1 site. We report that
      heterodimerization with c-Fos does not increase the binding of c-Jun to the uPA
      5'-TRE, in contrast to the increased binding at a consensus AP-1 site. Our data
      further suggest that c-Fos can act as a repressor of the c-Jun/ATF-2 binding
      site, revealing an important functional difference, with respect to canonical AP
      1 elements.

PMID- 7624152
TI  - Viability of wild type p53-containing and p53-deficient tumor cells following
      anticancer treatment: the use of human papillomavirus E6 to target p53.
AB  - One of the mechanisms in which anticancer therapies function is to induce cell
      death by apoptosis. In this regard, the biological activity of p53 may be
      critical since the presence of p53 appears to play a role in apoptosis following
      genotoxic stress. In experimental systems using in vitro transformed primary
      cells, there is a direct correlation between the presence of p53 and apoptosis.
      For example, E1A/ras-transformed primary mouse fibroblasts are less viable and
      undergo apoptosis following genotoxic stress if these cells contain a wild type
      p53. In comparison, similarly transformed cells which are p53-deficient are more
      viable and will not undergo apoptosis under these conditions. Although these are
      important observations, it remains to be established whether there exists a
      similar relationship between the presence of wild type p53 and loss of cell
      viability following therapy in human tumour cells. One way to address this
      question is to target wild type p53 in human tumour cells using human
      papillomavirus E6 which mediates the degradation of wild type p53 through the
      ubiquitin pathway. In this manner, E6 engineered p53-deficient and parental p53
      containing human tumour cells provides an appropriate experimental system in
      which to determine whether wild type p53 in tumour cells has influence on cell
      viability following genotoxic anticancer treatments. In the present study, the
      wild type p53 protein in human fibrosarcoma HT1080 cells were targeted with HPV
      18 E6 and the viability of these cells in response to treatment with adriamycin,
      u.v.-irradiation and gamma-irradiation was examined. Data is presented which
      shows that p53-containing and p53-deficient cells were equally sensitive to these
      treatments. These data argue that the wild type p53 in these tumour cells does
      not cause these cells to be less viable when treated with anticancer agents or
      u.v.-irradiation. Therefore, the status of p53 alone in tumour cells may not be
      an indicator of response to anticancer treatments.

PMID- 7624153
TI  - The tumor suppression function of p21Waf is contained in its N-terminal half
      ('half-WAF').
AB  - The Waf-1 encoded protein, p21, mediates p53 suppression of tumor cell growth.
      Overexpression of p21 in the H1299 tumor cell line suppresses colony formation
      similar to that resulted from p53 overexpression. In an effort to localize the
      tumor suppression function within the structure of p21 we utilized vectors
      constructed with systematic truncations of p21 and tested their efficiency in
      suppressing tumor cell growth. We demonstrate that the N-terminal half of the p21
      molecule (residues 1-80 and 1-89) shows better tumor cell growth suppression than
      the entire p21 molecule whereas the C-terminal half of p21 does not show this
      effect. These results may have implications for gene therapy of cancer.

PMID- 7624154
TI  - The Ras suppressor RSU-1 localizes to 10p13 and its expression in the U251
      glioblastoma cell line correlates with a decrease in growth rate and tumorigenic
      potential.
AB  - Rsu-1, which was isolated based on its ability to suppress transformation by v
      Ras, is a highly conserved gene which shares homology with yeast adenylyl cyclase
      in the region required for activation by Ras. Genomic DNA clones of human RSU-1
      have been isolated and used as a probe for fluorescence in situ hybridization
      (FISH) to assign RSU-1 to 10p13, confirming the previous results of somatic cell
      hybrid mapping localizing RSU-1 to chromosome 10. Screening of more than 20 human
      tumor cell lines for RSU-1 expression revealed that most cell lines contained
      abundant RSU-1 RNA and protein. However, the p33 RSU-1 protein was undetectable
      in the U251 glioblastoma cell line and transfection of a rsu-1 expression vector
      into U251 cells yielded a cell line in which rsu-1 was under the control of a
      regulatable metallothionein promoter. Addition of Cd2+ to the U251-Rsu-1
      transfectant resulted in transcription of rsu-1 RNA and the accumulation of p33
      Rsu-1 protein. Appearance of the Rsu-1 protein correlated with a reduction in
      growth rate of the U251-Rsu-1 transfectant. In addition, reduction in anchorage
      independent growth and phenotypic alteration in U251-Rsu-1 transfectant agar
      colonies was observed. Two U251-Rsu-1 transfectant cell lines were non
      tumorigenic when injected subcutaneously into athymic nude mice. These results,
      in conjunction with the frequent deletions observed in chromosome 10 in
      glioblastomas, suggest that RSU-1 loss of function may play a role in the
      progression of this disease.

PMID- 7624156
TI  - What rationale did the ONCC Board of Directors use to decide the eligibility
      criteria for the Advanced Oncology Nursing Certification Examination?

PMID- 7624155
TI  - Germline p16INK4A mutation and protein dysfunction in a family with inherited
      melanoma.
AB  - The gene encoding the cell cycle inhibitor p16INK4A (also known as p16, MTS1,
      CDKN2 and INK4) has been mapped to human chromosome band 9p21, a region that also
      contains a putative melanoma susceptibility gene. Although germline mutations in
      the coding region of the p16INK4A gene have been detected in some families with
      inherited melanoma, many other families show no evidence of such mutations and
      hence the role of p16INK4A in the development of this tumor is still unclear. In
      this report, we describe a family with inherited melanoma in which a novel
      mutation in exon 2 of the p16INK4A gene segregates with the disease. The mutant
      gene encodes a protein with an in-frame deletion of two amino acids (Asp96 and
      Leu97). We show that the mutant protein is functionally abnormal: it is unable to
      bind cdk4 in vitro and does not inhibit colony formation in tertiary passage rat
      embryo fibroblasts. Moreover, in a metastatic lesion from one patient the wild
      type p16INK4A allele was deleted and the mutant allele retained. We conclude that
      family members carrying this germline mutation in the p16INK4A gene are
      predisposed to melanoma. By extension, these findings implicate the p16INK4A gene
      in the development of some cases of familial melanoma.

PMID- 7624157
TI  - Expression of the Plasmodium berghei ookinete protein Pbs21 in a baculovirus
      insect cell system produces an efficient transmission blocking immunogen.
AB  - A surface protein of Plasmodium berghei ookinetes, Pbs21, was expressed in a
      baculovirus-insect cell system in cell culture and in Heliothis virescens larvae.
      Groups of BALB/c mice received two intraperitoneal inoculations of either i) Tris
      buffer or homogenized H. virescens larvae infected with wild-type baculovirus;
      ii) enriched, homogenized ookinetes, or iii) homogenized H. virescens larvae
      expressing recombinant Pbs21 (rPbs21). All animals immunized with ookinetes or
      with rPbs21 had high titres of antibodies (IgG isotype) that bound to native
      Pbs21. The large majority of antibodies in immune sera of both groups recognized
      the antigen under non-reducing but not under reducing conditions. The predominant
      IgG-subclasses in mice immunized with ookinetes was IgG1 and in mice immunized
      with rPbs21, the subclasses were IgG1 and IgG2a. Immunization with rPbs21 reduced
      the infectivity of P.berghei to mosquitoes by 91% compared to a 99% reduction
      following immunization with ookinetes. This preliminary data indicate that rPbs21
      expressed in this eukaryotic system induces a transmission-blocking immunity,
      which is more effective than that achieved using rPbs21 expressed in Escherichia
      coli (Matsuoka et al. 1994).

PMID- 7624158
TI  - Clethrionomys glareolus, but not Apodemus flavicollis, acquires resistance to
      Ixodes ricinus L., the main European vector of Borrelia burgdorferi.
AB  - The European rodents Clethrionomys glareolus (bank vole) and Apodemus flavicollis
      (yellow-necked-mouse) are important hosts of the tick species Ixodes ricinus, the
      main European vector of Borrelia burgdorferi. We have addressed the question
      whether or not these tick hosts develop resistance to I. ricinus larvae. C.
      glareolus and A. flavicollis were exposed to 40 I. ricinus larvae for five
      consecutive times at two week intervals. Resistance was tested by the following
      parameters: percentage of ticks fully engorged, time of attachment, engorgement
      index, percentage of recovered ticks and proportion of larvae moulting to nymphs.
      Repeated infestation of C. glareolus resulted in progressive and significant
      reductions in the percentage of fully engorged ticks, the time of attachment of
      partially engorged ticks, the scutal index of partially engorged ticks and the
      moulting success. In contrast, repeatedly infested A. flavicollis did not acquire
      resistance to larval I. ricinus. Effects of resistance in C. glareolus could be
      partially disrupted by treatment with the immunosuppressive agent, cyclosporin A
      (CsA), indicating that T helper cells participate in the immune responses to tick
      bites. The data suggest that acquired immunity to I. ricinus larvae in C.
      glareolus is a density-dependent factor regulating natural tick burdens and that
      it may have an impact on the transmission cycle of B. burgdorferi in Central
      Europe.

PMID- 7624159
TI  - IL-10 mediates immunosuppression following primary infection with Toxoplasma
      gondii in mice.
AB  - Suppression of the host immune response by Toxoplasma gondii has been observed in
      both human and experimental murine infection. In this study, inbred mice were
      infected with T. gondii. At day 7 post-infection, the lymphoproliferative
      response to both mitogen and superantigen as well as parasite antigen were found
      to be significantly depressed. Using a transwell system, it was determined that
      the reduced proliferative response was due to soluble factor(s) being expressed
      by splenocytes from the infected mice. Isolation of the splenocytes into an
      adherent and nonadherent population suggested that both macrophages and T cells
      were able to produce at least one soluble factor. Tissue culture supernatant
      derived from the splenocytes of the infected mice contain increased levels of IL
      10, whereas measurable IL-2 levels could not be quantitated. At day 7 post
      infection, both a biologic assay for IFN-gamma in culture supernatant and the
      expression of IFN-gamma mRNA in the splenocytes were reduced. Antibody to IL-10
      was able to partially neutralize (almost 50%) the in vitro immune downregulation
      of the tissue culture supernatant. Anti-IL-10 in combination with a nitric oxide
      (NO) antagonist was able to reverse the inhibitory activity of the culture
      supernatant by 85%. Since IL-10 is a potent antagonist of IFN-gamma, it may
      represent a critical cytokine involved in mediating T. gondii induced
      immunosuppression in the infected host.

PMID- 7624160
TI  - Differential effects of Trypanosoma cruzi on the transcription of the p55IL-2R, c
      fos, c-myc and CD69 genes in activated human lymphocytes.
AB  - Mitogen-activated lymphocytes co-cultured with either purified Trypanosoma cruzi
      trypomastigotes or the filtrate of trypomastigote suspensions in culture medium
      manifest a significant decrease in their capacities to express p55 interleukin-2
      receptor molecules (p55IL-2R) on their membrane and proliferate. In this study we
      found that the cytoplasmic levels of p55IL-2R are also markedly reduced under
      these conditions. This inhibition appeared to result from altered gene
      transcription since the levels of p55IL-2R mRNA in phytohaemagglutinin (PHA)
      stimulated human peripheral blood mononuclear cells (PBMC) dropped substantially
      in the presence of parasite suspension filtrate. The rates of decay for p55IL-2R
      mRNA determined in cultures lacking and containing the parasite filtrate after
      addition of actinomycin D to inhibit further RNA synthesis were comparable. These
      results indicated that decreased p55IL-2R mRNA was not due to decreased stability
      of this mRNA under our conditions and pointed to a transcriptional or pre
      transcriptional modification as the likely mechanism by which T. cruzi affects
      activated lymphocytes. The parasite filtrate did not appear to affect
      transcription of c-fos or c-myc (known to occur in the very early stages of
      lymphocyte activation) or that of CD69 (which is concomitant with p55IL-2R
      transcription). Thus, decreased p55IL-2R gene transcription appears to be a
      somewhat selective effect of a T. cruzi-derived molecule(s) rather than the
      consequence of an overall shutdown of gene transcription.

PMID- 7624161
TI  - Trypanosoma cruzi-induced decrease in the level of interferon-gamma receptor
      expression by resting and activated human blood lymphocytes.
AB  - A substantial proportion of human peripheral blood mononuclear cells (PBMC)
      manifested a decreased capacity to express membrane interferon-gamma receptors
      (IFN-gamma R) when co-cultured with Trypanosoma cruzi. Among the lymphocytes, B
      cells accounted for the bulk of this effect, evidenced by a marked drop in the
      proportion of CD19+ or CD20+ cells expressing IFN-gamma R. Decreased IFN-gamma R
      expression by B lymphocytes was seen as early as 3 h after co-culture with T.
      cruzi and persisted for at least 24 h. The parasite had no detectable effect on
      CD19, CD20 or DR antigen expression by B lymphocytes. Neither the proportion of B
      cells expressing these markers nor the membrane density of these molecules varied
      significantly in the presence of T. cruzi. In PBMC cultures stimulated with
      Staphlyococcus aureus Cowan I (SACI), T. cruzi decreased the percentages of both
      IFN-gamma R+ and IFN-R+bright (cells expressing above-normal levels of surface
      IFN-gamma R) B lymphocytes. Cell-free filtrates of T. cruzi suspensions
      reproduced the suppressive effects of living parasites on IFN-gamma R expression
      by B cells. When T. cruzi present, the intracellular levels of IFN-gamma R
      molecules in resting or SACI-activated B lymphocytes, represented by fluorescence
      intensity, were well below control values, suggesting that decreased surface
      expression resulted from suppressed IFN-gamma R synthesis. Among T (CD3+) cells,
      10.8% to 39.6% (7 donors) expressed surface IFN-gamma R and did so at a very low
      level. These percentages were also reduced by T. cruzi.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7624162
TI  - Lack of an association between hydatid disease and autoimmunity.
AB  - The prolonged survival of Echinococcus granulosus within the human host indicates
      that some mechanism is operating to permit parasite evasion of the host immune
      response. Several publications have described autoimmune phenomena in patients
      infected with hydatid cysts. The aim of this study was to test the postulate that
      there is a higher prevalence of autoantibodies in serum from patients with
      hydatid disease than in control samples, and this may provide some evidence of an
      association between autoimmunity and E. granulosus infection. Sera from 70
      patients with hydatid disease and 45 control subjects were assayed for the
      presence of antinuclear antibodies (ANA), tissue specific autoantibodies and
      rheumatoid factor. All patients were aged between 20 and 80 years of age with no
      known history of autoimmune disease. Hydatid patients were surgically confirmed
      cases. Control subjects were chosen on the basis that they were age and sex
      matched to the test sera and had no known illness at the time blood samples were
      obtained. On the basis of an ANA autoantibody titre of > 1:40 being regarded as
      positive, 19 (27%) of the hydatid patients, 13 (28%) of the controls were
      positive. Low levels of tissue specific autoantibodies and rheumatoid factor were
      detected in sera from 5 (7%) and 2 (11%) hydatid patients and 4 (8%) and 3 (16%)
      of control subjects respectively. No significant differences (P > 0.05) were
      found between autoantibody levels in the hydatid patient sera and the controls.
      These findings suggest that there is no association between hydatid infection and
      the level of autoantibodies to a broad range of self antigens.

PMID- 7624163
TI  - [The influence of the initial prednisone treatment period on the adrenal function
      and the further course of the disease in steroid sensitive nephrotic syndrome in
      children].
AB  - All together 184 children with the first attack of steroid sensitive nephrotic
      syndrome were included in the study: 44 were treated with prednisone for two, 68
      for three and 72 for six months. All of them completed a two years follow-up
      period. In 67 the results of treatment were correlated with adrenocortical
      function evaluated by basal and Synacthen stimulated cortisol levels determined
      before and after treatment. Treatment results were expressed as: percentage of
      children in sustained remission at the second year, percentage of children
      relapse-free within the first six months, and the whole follow-up period, and
      average number of relapses per patient per year. The best results were obtained
      in children treated for six months, while the results obtained in those treated
      for two and three months were significantly worse. In 67 children studied no
      significant correlation between suppression of adrenocortical function and either
      treatment duration or tendency for early relapse was found. That, the six months
      initial prednisone treatment period which is effective and safe, should be
      recommended for steroid sensitive nephrotic syndrome in children.

PMID- 7624165
TI  - [Risk factors of late ventricular arrhythmias after total correction of tetralogy
      of Fallot in children].
AB  - The authors present an analysis of pre-, intra- and postoperative risk factors of
      late ventricular arrhythmias in 100 children in 5-12 years after total correction
      of the tetralogy of Fallot. Complex arrhythmias (III-V class according to Lown
      classification) were found in 19% of patients. Risk factors were: in the pre- and
      intraoperative period--marked endocardial fibrosis of the right ventricular
      outflow tract, long bypass time (> 180 min) and aortic cross-clamp (> 90 min), in
      the post-operative period-left ventricular dysfunction in echocardiographic
      examination and age > 10 years at time of the study. Complex ventricular
      arrhythmias were more frequent in patients with associated supraventricular
      arrhythmias and with progressive bundle branch block.

PMID- 7624164
TI  - [The influence of hepatitis B vaccine dose on direct results of hepatitis B
      vaccination in children with nephrotic syndrome].
AB  - In the first phase of the study on the efficacy of vaccination against hepatitis
      B with a double dose of the vaccine in children with steroid-sensitive nephrotic
      syndrome (NS), the best results were obtained in the group of patients in
      remission of NS. The aim of the present study was to compare the efficacy of
      standard and double doses of the vaccine in patients in remission. After
      excluding HBV infection, recombinant hepatitis B vaccine was administered i.m.
      according to the 0, 1, 2 month protocol in a standard dose in group I and a
      double dose in group II. In both groups the seroprotection rate was similar (I
      group-96%, II group-93%), however the anti-HBs antibody level was significantly
      higher in group II during a 3 month observation period.

PMID- 7624166
TI  - [Evaluation of +ondansetron (Zolfiran) in prevention of vomiting in children
      treated with cytostatics].
AB  - The evaluation of Zofran in prevention of chemotherapy induced vomiting was
      performed in 37 children treated for neoplasms during 167 courses of
      chemotherapy. Good efficacy was shown in 90% of the evaluated courses. Our
      results suggest that Zofran is effective and well-tolerated, therefore it should
      be a drug of choice in prevention of chemotherapy induced vomiting.

PMID- 7624167
TI  - [The occurrence of congenital abnormalities in children under 2 years of age in
      Zielona Gora province between 1987-1992].
AB  - The analysis encompassed 1278 children under 2 years of age with congenital
      abnormalities from a group of 60, 815 live-born neonates in Zielona Gora province
      between 1987-1992. The population prevalence of congenital abnormalities was
      2.10% on average. Cardiovascular system abnormalities were the most frequent,
      making up 40.53% of all detected abnormalities and 0.85% of the analyzed
      population. The successive positions were abnormalities of: the limbs (15.41% of
      all detected abnormalities and 0.31% of the analyzed population), genitourinary
      system (9.08% and 0.19% respectively), central nervous system (7.51% i 0.16%) and
      digestive system (6.57% and 0.14). There were no statistically significant
      differences between sexes, towns and villages, jobs of mothers and months of
      birth. Congenital abnormalities were twice as frequent (4.83%) in low-birth
      weight neonates. Deaths caused by congenital abnormalities made 30.9% of total
      infantile mortality. 66% of children with congenital abnormalities (mainly heart
      defects) died in first month of life.

PMID- 7624169
TI  - [The psychosomatic development of children who recovered from secondary
      malabsorption syndrome].
AB  - The study encompassed 100 children who recovered from secondary malabsorption
      syndrome. The following were evaluated: physical development (body weight,
      height, skin-fold thickness on the arm, shoulder-blade and abdomen) and IQ in the
      Wechsler scale. Children who had suffered from secondary malabsorption syndrome
      in infancy showed lower parameters of physical development compared with healthy
      children. These differences pertained mainly to body weight and height and to the
      intelligence quotient.

PMID- 7624168
TI  - [Fecal flora in infants at the beginning and the end of hospitalization].
AB  - The feces of 52 children without diarrhea, aged from 5 days to 22 months, treated
      in the Department for various causes was investigated for the presence of that
      might be the cause of infectious diarrhea. Samples were taken at the beginning
      and the end of hospitalization. The results were analyzed with reference to 5 age
      subgroups (1 month, 2-3 months, 4-6 months, 7-12 months, 12-22 months) and
      duration of hospitalization (3-42 days). The presence of potentially pathogenic
      bacteria in the feces was found in 87% of children without diarrhea, especially
      at the beginning of hospitalization, which suggests the possible existence of a
      "transient carrier state". Because of the immaturity of a number of intra
      organism mechanisms, the presence of pathogenic bacteria in the alimentary tract
      in the youngest children, may be a potential danger of developing serious, even
      generalized disease processes and may constitute an important source of
      nosocomial infections.

PMID- 7624172
TI  - [What to choose? On the rational use of diagnostic imaging in pediatrics].
AB  - Dynamic development and progress in diagnostic imaging imply the rational use of
      diagnostic methods and their clinical applications. The choice of diagnostic
      techniques, especially in pediatrics, is still of fundamental importance. Proper
      indications for diagnostics may reduce the invasiveness of diagnostic procedures.

PMID- 7624171
TI  - [Cystic fibrosis: now and in the future].
AB  - The paper describes the genetic and pathophysiological basis of cystic fibrosis.
      The most frequent manifestations of the disease are listed and the currently
      available therapeutic options, both causal and symptomatic, are presented.
      Special emphasis is placed on the often underestimated nutritional management.
      The role of multidisciplinary teams and of the active involvement of patients and
      their families is stressed. The creation of a coherent cystic fibrosis health
      care system (both in paediatrics and internal medicine) on a regional and nation
      wide scale will undoubtedly play an important role in successful treatment.

PMID- 7624170
TI  - [Evaluation of treatment efficacy in gastritis and duodenitis in children with
      Helicobacter pylori infection].
AB  - The efficacy of Ventrisol treatment in gastritis and duodenitis in children
      infected with Helicobacter pylori was evaluated. Eighty-six children aged 3 to 18
      years with chronic abdominal pain were examined. All children underwent
      gastrofiberoscopic examination. H. pylori infection was diagnosed on the bases of
      two of three diagnostic tests (urease, bacteriological, histological). H. pylori
      was detected in 50 children (56.4%). After a 4 week course of Ventrisol
      treatment, H. pylori eradication was obtained in 41 children (82%). Twenty-one
      children (42%) were completely cured, whereas in 20 children (40%) elimination of
      HP was observed although macroscopic and histological inflammatory changes were
      still present. The drug was well tolerated by 92.5% of children and its
      accumulation was not observed.

PMID- 7624173
TI  - [Diagnostic problems of congenital muscular dystrophies in children].
AB  - Three children with a diagnosis of congenital muscular dystrophy are described.
      Because of the heterogeneity of these disorders the authors stress the necessity
      of differentiation with other causes of "floppy infant" syndrome, especially with
      Werdnig-Hoffmann disease, structural myopathies, and Duchenne progressive
      muscular dystrophy. An extensive hypodense area on brain CT scan was found in one
      child.

PMID- 7624174
TI  - [Elevation of alanine aminotransferase concentration in the serum: one of the
      symptoms of muscular dystrophy].

PMID- 7624175
TI  - [Enterocolitis necroticans in a neonate from a twin pregnancy with intrauterine
      death of the fetus].
AB  - The turbulent perinatal period in a neonate from a pregnancy with intrauterine
      death of one fetus is described. The live fetus was born in the 37th week of
      pregnancy after the macerated twin was delivered spontaneously. Convulsions,
      hypocalcemia, thrombocytopenia and enterocolitis necroticans were observed during
      the neonatal period.

PMID- 7624176
TI  - [Slow development of multiorgan tuberculosis in an infant].
AB  - Slowly developing tuberculosis in a BCG-vaccinated infant was analysed in a 2
      month-old child suffering from cervico-lymphadenitis. It was diagnosed after 8
      months period of non-specific treatment as tuberculosis. Further observation
      revealed severe forms of disease-miliary tuberculosis and meningoencephalitis.
      Familial contact with tuberculosis was established. The outcome after 9 months of
      anti-tuberculosis therapy was successful.

PMID- 7624177
TI  - [A rare form of granuloma annulare].
AB  - We present a four-year-old girl with a doubly rare form of granuloma annulare
      with non-typical localisation of superficial nodules on the palms and
      predisposition to ulceration which is very rare in this type of superficial
      nodules. The diagnosis was proved by histological examination. After the local
      cryotherapy (ethyl chloride) the lesions almost completely disappeared.

PMID- 7624178
TI  - [Microbiological evaluation of effectiveness of antibacterial drugs for the acute
      inflammation of the middle ear].

PMID- 7624180
TI  - Cognitive complexity and scanning by Chinese and American students in an American
      university.
AB  - 75 Chinese and 75 American students' perceptual styles of cognitive complexity
      and scanning (focus versus nonfocus) were analyzed. The American students, 22
      Chinese women, and 18 Chinese social science and humanities students scored as
      more complex than the 53 Chinese men and 57 Chinese natural science and
      engineering students. It was also observed that the Chinese men and American
      women scored as more focused than the 22 Chinese women and 43 American men.

PMID- 7624179
TI  - Severity of injuries in trauma patients.
AB  - The present purpose was to illustrate the range of severity scores among trauma
      patients. A computerized conversion of ICD-9CM injury diagnoses into scores for
      severity of injury was processed on data of 36,178 trauma patients. More than 94%
      of the patients had injuries of minor severity. The probability of mortality was
      .67 when the Injury Severity Score (ISS) was > or = 16.

PMID- 7624181
TI  - WAIS Digit Symbol and Block Design scores in abstinent alcoholics: a replication.
AB  - Previous work has indicated that alcoholics perform more poorly on the Finnish
      WAIS Block Design than on the Digit Symbol. The purpose of the present study was
      to replicate that result. A total of 75 Finnish alcoholic men took part. The same
      kind of asymmetry was found between the tests, scores on the Block Design being
      poorer than those on Digit Symbol.

PMID- 7624182
TI  - A size illusion from simultaneous changes in length and direction of a line
      pattern.
AB  - A circle was attached to one of three lines which were changing in length and
      direction simultaneously. This configuration of moving lines had been found
      previously to induce the perception of depth. Of 26 observers 20 reported that
      the moving circle appeared smaller in size than a physically equal stationary
      circle which was located outside the changing, depth-inducing configuration.

PMID- 7624183
TI  - Use of individual differences questionnaire with psychiatric inpatients.
AB  - Paivio's Individual Differences Questionnaire was given to 47 psychiatric
      inpatients. Their mean verbal and imagery scores were higher than those for
      Paivio and Harshman's 713 students. Also, the latter had higher verbal than
      imagery scores, while the psychiatric group had the opposite. Subjects with
      affective disorders had significantly higher mean scores on a subscale which
      measures vividness of dreams, day-dreams, and imagination than other diagnostic
      groups.

PMID- 7624184
TI  - Nostalgia: a psychological perspective.
AB  - A survey was designed to assess nostalgia for 20 aspects of experience as well as
      relative judgments of the world past, present, and future. Surveys were completed
      by 648 respondents, 268 males and 380 females, ranging in age from 4 to 80 years
      old. Split-half reliability was .78. Test-retest reliability over a 1-wk.
      interval on a separate sample of 50 respondents was .84. Nostalgia was related to
      the judgment of the past relative to the present. Gender differences were not
      significant, but significant differences across age groups were obtained for most
      items. The intensity of nostalgic sentiment varied across objects, situations,
      aspects of society, and people. Factor analysis suggested that nostalgia is
      comprised of a number of factors reflecting different spheres and levels of
      experience. For nostalgia, conceptualized as a multifaceted, composite construct,
      results were discussed with respect to four approaches--generational,
      developmental, personality, and transient mood state. Suggestions were made for
      further development of the survey and for research exploring relationships among
      nostalgia, motivation, emotion, and behavior.

PMID- 7624185
TI  - Perceptual collapse of three-dimensional structure from motion parallax.
AB  - This study concerned how perceived depth collapses after asymptotic depth is
      reached and the information specifying depth is abruptly removed. The stimuli
      were random-dot, computer-generated three-dimensional objects and the depth
      information was motion parallax. Motion parallax was removed in two ways. In the
      first method, the depth of all object points was reassigned to zero, simulating a
      disk. In the second method, a rotation of the object was introduced in such a way
      that a degenerate case of motion parallax was produced. The results showed that
      judgments of depth slowly collapsed once motion parallax was removed. Over-all,
      judgments of depth required about the same duration to collapse as was required
      for the judgments to build up to asymptotic levels (about 750 msec.). Finally,
      depth collapsed more slowly when the motion parallax was removed by redefining
      the object as a disk than when removed using the other method.

PMID- 7624186
TI  - Information processing and concentration as a function of fitness level and
      exercise-induced activation to exhaustion.
AB  - To examine the effects of increasing amounts of exercise on attention and speed
      of information processing 20 paid male subjects were separated into groups of
      high and low fitness according to their VO2max values. The experiment involved an
      attentional task (Random Number Generation) that was given after every 10 min. of
      cycling at work-load resistances calculated as 40%, 50%, 60%, 70%, and 80% of
      individual VO2max values. An eight-choice reaction time-movement time task was
      given before and after exercise as well as after a 15-min. recovery period.
      Individuals were tested within 10 min. after exercise cessation (exhaustion) for
      concentration and within 15 min. for choice reaction time and movement time to
      assess whether fitness differentially interacted with these variables. Split-plot
      factorial analyses of variance suggested that the CNS appeared capable of
      maintaining performance after 50 min. of exhaustive exercise compared to values
      obtained at the preexercise condition. A 15-min. recovery period significantly
      impaired MT but relatively highly fit individuals did not appear to perform the
      choice RT and concentration tasks better than individuals low in fitness.

PMID- 7624188
TI  - Sit-to-stand test for measuring performance of lower extremity muscles.
AB  - When the intent is to quantify performance of lower extremity muscles, the sit-to
      stand test is a practical alternative to manual muscle testing and various
      instrumented options. Several procedures for performing the test are presented in
      this review as is information relevant to test interpretation. Performance
      variables known to be associated with sit-to-stand performance are noted.

PMID- 7624187
TI  - Creativity and affective illness: an objection.
AB  - A good deal of attention has recently been given to two studies purportedly
      showing a connection between creativity and affective illness. In both cases,
      there have been inadequate (or absent) controls, biased selection procedures,
      single interviewer-experimenter bias, and, in one study, misrepresentative use of
      statistics. We have published contrary experimental results which, on a
      statistically significant level, differentiate creative thinking and creativity
      from psychopathological modes of response.

PMID- 7624189
TI  - Expectancy for change and adaptation to a new signal probability.
AB  - An experiment showed that the higher the 18 observers' expectancy for change in
      signal probability (without knowing the future probability), the more successful
      the adaptation to a new probabilistic environment in terms of shift in response
      criterion.

PMID- 7624190
TI  - Effects of occluded vision and imagery on putting golf balls.
AB  - This study examined the effects of combining occluded vision with imagery for
      acquiring and retaining golf-putting skill in a college class of 80. The findings
      indicated that college students who registered for beginning golf classes were
      significantly higher in putting-skill acquisition using occluded vision and
      visual imagery than practicing while in visual contact with the ball and no
      imagery. Occluded-vision imagery was not superior to visual imagery for
      acquisition or retention of putting skill. In addition, the occluded-vision
      subjects showed positive transfer to visual putting skills.

PMID- 7624191
TI  - Trail Making Test norms for psychiatric patients.
AB  - The Trail Making Test was administered to a sample of 661 inpatients in a
      publicly supported psychiatric hospital. The patients' mean IQ of 83.7 (SD =
      13.0) was in the low end of the low average range. Multiple regression analysis
      of the scores showed significant IQ and age components of Trail Making Test
      scores; however, education and gender differences in performance were not
      significant once IQ and age were factored into the regression equation. Ability
      based norms using time in seconds to completion as the score and IQ as a
      moderator variable are presented. Such norms allow more appropriate evaluation of
      the differential cognitive functioning of this population than previously
      published norms. Normal standard score conversions from raw scores, the
      intercept, regression weights for IQ and age, and standard error of the
      regression for both the Trails tasks are provided for individuals desiring to
      write a program to provide scores corrected for IQ and age.

PMID- 7624193
TI  - Effects of inconsistent pictures on remembering text.
AB  - An experiment was conducted to examine whether a consistent or an inconsistent
      picture would facilitate recall of text when recall was tested under two
      conditions involving a consistent or an inconsistent picture. Analyses indicated
      that recall in the inconsistent-picture condition was better than that in the
      consistent-picture condition for missing sentences but not for complete sentences
      of text. This result suggests that an inconsistent picture may facilitate
      processing of textual information more elaborately than do consistent pictures.

PMID- 7624192
TI  - Does psychological refractoriness depend on the similarity of the required
      responses?
AB  - The purpose of this study was to examine whether the similarity of R1 and R2 is a
      moderating variable in the psychological refractoriness effect. 10 subjects were
      required to react and produce the sequence of two homogeneous or heterogeneous
      peak forces as soon as possible after Stimulus 1 and 2 separated by variable
      interstimulus intervals. The heterogeneous condition produced a significantly
      longer RT and premotor time to Stimulus 2 than the control condition for the
      intervals up to 200 msec. The homogeneous condition, however, produced a
      significantly shorter RT and premotor time to Stimulus 2 than the control
      condition when the intervals were from 100 to 1000 msec. These findings suggest
      that the psychological refractoriness effect depends on the similarity of the
      required responses. These results were discussed from the view of a limited
      capacity mechanism during the response-programming stage.

PMID- 7624194
TI  - Electrodermal palmar asymmetry and nostril dominance.
AB  - The present work tested the usefulness of combined bilateral palmar skin
      potential and nostril dominance measures as indices of relative hemispheric
      activation. These measures are easy to obtain and, when used in tandem, may
      provide inexpensive and quick indices of relative hemispheric activation for the
      researcher interested in laterality, but with limited resources. Bilateral
      electrodermal palmar measurements were made and synchronous nostril dominance was
      recorded for one experienced subject (the author). A total of 760 individual skin
      resistance measures were taken for a period of 26 days from 7 a.m. to midnight.
      Higher right-hand conductance measures were recorded than the left-hand measures.
      Electrodermal palmar asymmetry was confirmed during the right-nostril condition,
      whereas more symmetrical palmar recordings were obtained during the left-nostril
      condition.

PMID- 7624195
TI  - Age-related changes in natural and fast walking.
AB  - Age-related changes in the relation between natural and fast walking were
      investigated for 69 healthy women aged 21 to 88 years. The ratio (fast/natural)
      of both walking velocity and cadence declined significantly across age groups.

PMID- 7624196
TI  - Factor structure of the California Verbal Learning Test in moderate and severe
      closed-head injury.
AB  - A factor analysis with principal components extraction and varimax rotation was
      performed on 19 California Verbal Learning Test age-uncorrected scores from a
      sample of 75 moderate and severe closed-head-injured patients. A 6-factor
      solution was obtained that accounted for 80% of the total variance and was
      similar to those reported previously. The factors were labeled General Verbal
      Learning, Response Discrimination, Learning Strategy, Proactive Effect, Self
      monitoring, and Serial Position. Factor scores were derived and correlated with
      other neuropsychological measures. The General Verbal Learning factor scores were
      significantly correlated with those on measures of memory, complex attention, and
      strategy induction.

PMID- 7624197
TI  - Effects of different colored test environments on selected physiological and
      psychological responses during maximal graded treadmill tests.
AB  - The belief that color may have many varied effects on the human organism has been
      well-established. Very little, however, has been done to look at responses to
      color during exercise. 15 subjects performed three maximal graded treadmill
      tests, once in each of three different colored environments. Five physiological
      and one psychological variables were measured during the three exercise periods.
      No significant differences were found among conditions.

PMID- 7624198
TI  - Startle eyeblink elicitation in attention deficit disordered children using low
      intensity acoustic stimuli.
AB  - The acoustic startle eyeblink response was measured in 11 pediatric psychiatric
      inpatients, 7 diagnosed with Attention Deficit Hyperactivity Disorder (ADHD) and
      4 diagnosed with other conditions (non-ADHD). Startle stimuli were 85 or 95 dB
      SPL, 50-msec. noise pulses. Startle eyeblink responses were reliably measured for
      all children. Startle response latency was faster for ADHD children than for
      clinical control subjects in all stimulus conditions. These data show that the
      acoustic startle eyeblink response can be reliably elicited in ADHD children at
      lower intensities (85-95 dB) than those used in previous published research (104
      dB). This may increase the use of the startle paradigm, since less intense
      stimuli may be less disturbing to the children, increasing compliance and
      allowing longer testing sessions.

PMID- 7624199
TI  - Chinese and American students' perceptual styles of field independence versus
      field dependence.
AB  - The Group Embedded Figures Test of Oltman, Raskin, and Witkin was administered to
      75 Chinese and 75 American students at an American university to measure their
      perceptual styles of field independence versus field dependence. The analysis
      showed that these students had a similar style of field independence.

PMID- 7624200
TI  - Probing collinearity bias in the close induction field.
AB  - The substrates of the Poggendorff illusion can be evaluated using as few as two
      line segments, a test segment whose collinearity is judged, and an induction
      segment which serves to bias that judgment. Previous research from this
      laboratory has shown that a very short induction segment can produce a
      substantial bias of perceived collinearity when it is centered at the tip of the
      test segment, and there is some evidence that the symmetry of this configuration
      affects the strength of this bias. Four experiments were conducted to clarify the
      issue of symmetry in the stimulation of the "half-field" zones which lie on each
      side of the tip. That Exp. 1a showed displacements which moved the induction
      segment to an eccentric position, i.e., occupying a single half-field, reduced
      collinearity error. With additional displacement which produced a gap there was a
      rebound of induction effect. Exp. 1b indicated that an eccentric induction
      segment does not produce the usual strength or pattern of bias as a function of
      its orientation relative to the test segment. Exp. 2a suggested that the strength
      of induction effect is a function of symmetry within the half-fields rather than
      the lengths of the segments per se. Finally, in Exp. 2b the strength of induction
      was a joint function of the position of a short segment within one half-field and
      the length of another segment which stimulated the other half-field. The effect
      showed a complex oscillation with changes in position. We discuss the induction
      mechanism as beginning with "contour filters" which register the induction
      segment(s) and which combine their responses on the basis of "tandem activation"
      of the close half-fields.

PMID- 7624201
TI  - Readability analysis of health, physical education, recreation and dance journal
      articles.
AB  - The readability levels of 10 articles each from the Journal of Health Education,
      Journal of Physical Education, Recreation and Dance, Research Quarterly for
      Exercise and Sport, and Strategies: A Journal for Physical and Sport Educators
      were estimated. On average, the 40 articles were written at the college junior
      level (M = 14.9, SD = 1.6); however, significant between-journal differences were
      found, with between-journal effect sizes ranging from 0.36 to 3.64.

PMID- 7624202
TI  - Changes in ratings of perceived exertion and psychological affect in the early
      stages of exercise.
AB  - The purpose of this study was to examine differences in the rating of perceived
      exertion (RPE) and affect, as assessed by a bipolar feeling scale (FS) during
      cycle ergometry in a steady-state and a nonsteady-state condition in active and
      inactive individuals. 71 subjects completed a self-report questionnaire on
      physical activity and were assigned to two groups, a low-active group of 16 men
      and 18 women and a high-active group of 18 men and 19 women. On Day 1 all
      subjects completed a sub-maximal exercise test to predict maximum oxygen uptake
      (VO2max) from which work rates corresponding to 60% and 90% VO2max were
      calculated. On Day 2 half of the subjects completed a work rate equivalent to 60%
      VO2max whilst the other half completed a 90% VO2max work rate. On Day 3
      alternative work rates were completed. RPE and FS were recorded after 2 and 4
      min, at each work rate on both days. Mixed-model, 4-factor (gender x group x work
      rate x time) analyses of variance with repeated measures on work rate and time
      were conducted on the FS and RPE data. RPE was higher after 4 min, at both
      intensities, and there was a greater increase in RPE between 2 and 4 min, at the
      90% than the 60% work rate. Rated feeling was more positive at the 60% work rate,
      high-active subjects were more positive than low-active subjects and rated
      feeling was lower in Minute 4 for both groups. The following interactions were
      observed: rated feeling was more negative after 4 min. for the low-active group
      compared to the high-active group at 2 and 4 min. and the low-active group
      reported more negative feeling at the 90% work rate compared to the 60% work rate
      while the high-active group did not change significantly. Timing of the RPE is
      important if used to prescribe exercise intensity. Further, low-active subjects
      should be encouraged to exercise at moderate intensities and discouraged from
      focusing on how they feel immediately before they finish a session.

PMID- 7624203
TI  - Personality disorders and regulative styles of patients with temporo-mandibular
      joint pain dysfunction syndrome.
AB  - A sample of 42 women patients with Temporo-mandibular Joint Pain Dysfunction
      Syndrome was given the Millon Clinical Multiaxial Inventory-II and the Serial
      Color-Word Test. Compared with sex- and age-matched nonclinical controls, temporo
      mandibular patients had significantly (1) higher scores on the Obsessive
      Compulsive scale, (2) lower scores of ITa (a pattern concerned with initial times
      of response), and (3) higher scores of R (linear increase in reading times during
      the trials). The latter intergroup difference concerned mainly the first subtest,
      i.e., temporo-mandibular patients were characterized by higher scores of R from
      the very beginning of the process of adaptation.

PMID- 7624204
TI  - Blue versus periwinkle: color identification and gender.
AB  - This study examined the color identification and vocabulary skills of 101 female
      and 52 male college students. Femininity scores, color-related hobbies, and
      academic aptitude scores were also examined for their influence on color
      identification. The women identified significantly more elaborate colors than did
      the men. Color identification was significantly correlated with vocabulary but
      not with scores on femininity. Academic aptitude scores and having a color
      related hobby also predicted color identification under some conditions.

PMID- 7624205
TI  - Performance in component sports of triathlon events as a function of ability,
      age, and gender.

PMID- 7624206
TI  - Efficiency and proficiency of bimanual cranking: differences between two cranking
      patterns.
AB  - The efficiency and motor proficiency of an arm ergometer exercise were evaluated
      for two different cranking methods, cranking in the forward and reverse
      directions. 8 young men participated. Their heart rates were measured as an index
      of energy consumption. The proficiency of elbow-joint motion was assessed in
      terms of its consistency (intrasubject variability in cycle period, peak
      velocity, and peak acceleration) and smoothness (jerk cost). Heart rates and jerk
      costs were lower during exercise in the forward direction than in the reverse
      direction. These results suggest that improved efficiency accompanied improved
      motor proficiency in terms of smoothness of movement for arm ergometer exercises
      under different cranking conditions.

PMID- 7624207
TI  - Associations between academic performance of division 1 college athletes and
      their perceptions of the effects of anabolic steroids.
AB  - Data on the relationship between academic performance (grade point average) of
      college athletes and their perceptions of the effects of anabolic steroids on
      their sport and their performance were collected from Division 1 athletes (N =
      1,638) representing 12 varsity sports chosen from five universities nationwide.
      The response rate was 74%. Analysis yielded differences between athletes with
      high and low GPAs in perceptions of the effects of anabolic steroids. The lower
      the GPA, the less likely the athletes were to believe that anabolic steroids are
      a threat to health, are a problem in their sport, and are addictive. Also, they
      were more likely to believe that anabolic steroids enhance performance.

PMID- 7624208
TI  - Sequential tree method of examining the relationship between job stress and
      mental health.
AB  - Data from a study of 178 managers were analyzed by a sequential decision tree
      method which segmented the sample into homogeneous subgroups and gave insight
      into the relationships between job stress and mental health. Lack of needed
      information was the first stressor to divide the sample, followed, for the
      majority of managers, by acceptance by fellow workers, supervisors' evaluations,
      and conflicting demands.

PMID- 7624209
TI  - Does brief Aikido training reduce aggression of youth?
AB  - Over 2 1/2 weeks, 21 youth trained in beginning principles of Aikido were not
      rated lower on the Teachers' Self-control Rating Scale and on aggressive behavior
      than 21 students on a waiting list for a class; however, the several
      methodological limitations suggested conclusions on the effects of brief Aikido
      training on youths' aggressive behaviors are premature.

PMID- 7624210
TI  - Protective filters in the prevention of asthenopia at a video display terminal.
AB  - In this work 25,064 employees were studied with the aim of investigating whether
      the video display terminal (VDT) equipped with filters reduces the incidence of
      asthenopia with reference to weekly time spent at a VDT and duration of work at a
      VDT. Analysis showed that the filters themselves do not reduce the occurrence of
      asthenopia consequent to various factors (refractive defects, time spent at a
      VDT, and monitors' characteristics).

PMID- 7624211
TI  - Temporal locus of knowledge of results: a meta-analytic review.
AB  - Meta-analysis was performed to evaluate the temporal locus of knowledge of
      results. An extensive literature review was conducted, yielding 17 published
      articles suitable for the meta-analyses. These studies were then separated into 2
      general categories of acquisition and retention. These categories were subdivided
      further into KR delay interval, KR delay and motor interpolated activities, KR
      delay and verbal interpolated activities, post-KR interval, post-KR interval and
      motor interpolated activities, and post-KR interval and verbal interpolated
      activities. 6 of the 12 categories gave enough data for the meta-analyses. The
      categories which showed significant results were KR-delay, post-KR interval, and
      post-KR interval and verbal interpolated activities in acquisition. Although
      significant, effect sizes were comparatively small. The discussion of findings
      focused on effects of the temporal locus of KR and interpolated activities on
      performance and learning.

PMID- 7624212
TI  - Pain perception, coping strategies, and stress management among periodontal
      patients with repeated surgeries.
AB  - The relationships between coping strategies, stress response during periodontal
      surgery, and perceived pain after each of two surgical procedures were studied in
      42 adult women between the ages of 28 and 67 years. The presurgical use of coping
      by indirect action was positively correlated with decreased stress behavior
      during each surgery. The use of attention-coping strategies was significantly
      correlated with pain measures after each surgery, while avoidance-coping
      strategies were not. Age and patients' rating of pain were the best predictors of
      the use of attention coping. These findings suggest that preoperative preparation
      which includes information on enhancing attention-coping may assist some patients
      with postsurgical pain and discomfort.

PMID- 7624214
TI  - Affective reactions to failure as a function of effort and depression.
AB  - University students, divided on a quartile split into low (n = 53) and high (n =
      42) depression groups (Beck scores of 0-1 or 7 and higher), were presented a
      series of failure situations in which failure occurred under high effort (with
      situational factors causing failure) or low effort. Subjects rated their
      affective reactions to each situation. It was hypothesized that the group low on
      depression would feel worse after high effort (since this would challenge their
      sense of self-efficacy) whereas the high depression group would feel better in
      this condition (since attribution of failure to situational factors would protect
      their sense of self-esteem). Results were consistent with expectations for the
      group low on depression. For the group high on depression, the means were rank
      ordered as predicted but the difference was not significant.

PMID- 7624213
TI  - Screening for child-reported behavioral and emotional problems in primary care
      pediatrics.
AB  - In light of the findings that mother-completed checklists do not adequately
      reflect children's perceptions of their own adjustment, two child-completed
      questionnaires were assessed as screening measures for behavioral or emotional
      problems with 50 children seen for well-child examinations. Case criterion was
      child-reported DSM-III symptoms through a clinical interview. Support was
      provided for the Revised Children's Manifest Anxiety Scale but not the Children's
      Depression Inventory as a child-reported screening measure. Moreover, the
      findings indicated that both mother-completed and child-completed measures are
      needed to screen adequately for behavioral or emotional problems of children seen
      in a primary care pediatric clinic.

PMID- 7624215
TI  - Alternative Impairment Index: a measure of neuropsychological deficit.
AB  - The Alternative Impairment Index, a new composite measure of neuropsychological
      deficit, was compared with two established measures of neuropsychological
      impairment, the General Neuropsychological Deficit Scale and the Halstead
      Impairment Index. A sample of 25 brain-damaged patients with complete Halstead
      Reitan Neuropsychological Test scores was composed. Test scores on these measures
      were calculated for each patient. Severity criteria were set for normal, mild,
      moderate, and severe brain damage. Hit rates for agreement on severity for the
      Alternative Impairment Index and Halstead Impairment Index were 60%, i.e., 15/25,
      and for the General Neuropsychological Deficit Scale and Alternative Impairment
      Index were 64%, i.e., 16/25.

PMID- 7624216
TI  - Note on the role of negative affectivity in understanding relationships between
      self-reports of exercise and sick leave.
AB  - Previous research indicates that observed correlations between self-reports of
      job stress and self-reports of strain may be reduced after partialling out the
      variance due to the personality trait of negative affectivity. The present study
      examined the effect of negative affectivity on the relationships between self
      reports of exercise and strain in a sample of 128 governmental employees. While
      the magnitudes of the bivariate correlations between exercise and strain were
      small, the results of semipartial correlation analyses were somewhat consistent
      with expectations that the magnitudes of bivariate correlations between exercise
      participation and self-reports of strain would be reduced after controlling for
      negative affectivity in measures of strain. The implications of these findings
      for incorporating a measure of negative affectivity in studies of exercise-strain
      relationships involving self-reports are discussed.

PMID- 7624217
TI  - Transfer of odd-item search performance in a chimpanzee (Pan troglodytes).
AB  - An adult female chimpanzee (Pan troglodytes) who was trained only on odd-item
      search with a large number of items was tested for transfer of the odd-item
      search performance to new stimuli and to minimal items (1 target and 2 uniform
      distractors). The subject showed transfer to new target-distractor pairs when the
      number of items was large enough but showed no transfer to a minimal display even
      when the trained (old) target-distractor pair was presented. The results suggest
      that her performance on odd-item search was controlled mainly by perceptual cues
      such as pop-out of the target among the uniform distractors but not on relational
      cues such as the oddity rule.

PMID- 7624218
TI  - Three-dimensional kinematic analysis of baseball pitching in acceleration phase.
AB  - To examine the relationships of pitching performance to maximum external rotation
      of the shoulder and to time in the acceleration phase, 3 male baseball pitchers
      were tested using three-dimensional cinematography. Analysis indicated that
      increasing maximum external rotation of the shoulder at the very beginning of the
      acceleration phase would help to generate a higher pitching ball velocity since a
      greater linear and angular displacement could be used to accelerate the throwing
      forearm. Slowing the wrist action just before ball-release may be a key technique
      to increasing pitching velocity of the ball.

PMID- 7624219
TI  - Underestimation of subjects' monitored radial pulse rates following traumatic
      brain injury.
AB  - The measurement of heart rate is fundamental to the scientific programming of
      physical activity. In this analysis, 20 male subjects with traumatic brain
      injuries underestimated their heart rates as measured by the radial pulse both at
      rest and after brief, light exercise.

PMID- 7624220
TI  - Gender differences in eyewitness testimony.
AB  - One of the earliest empirical studies of sex differences in eyewitness behavior
      was that of William Stern (1903-1904). Stern's research furnished evidence in
      approbation of the long-held opinion that women's eyewitness testimony was less
      accurate and less resistant to the influence of misleading information than
      men's; however, Stern's 2 groups were not comparable in age. Other studies by
      Bringmann and colleagues in 1986 did not replicate Stern's findings using
      comparable age groups. The present investigation examined eyewitness behavior
      using two stimulus presentations of dissimilar content and complexity and tests
      for significance of gender differences. Subjects were 20 male and 20 female
      college students. No significant gender differences were found between groups on
      accuracy of recall or resistance to false information on the short-term memory
      task.

PMID- 7624221
TI  - Effect of continuous and intermittent exercise on energy expenditure and on the
      cardiorespiratory response.
AB  - Continuous exercise and intermittent exercise protocols, which are equated for
      the total work performed, result in similar energy expenditure and thus, in a
      similar oxygen consumption. Intermittent exercise-relaxation may enhance
      enjoyment and thereby increase compliance. However, the composite
      cardiorespiratory response to the two types of exercise programs is different,
      and this results in different cardiorespiratory adaptations.

PMID- 7624222
TI  - Vigilance as a table of numbers.
AB  - Data from vigilance experiments have structure. Its bases include 1/12 and
      multiples thereof, single-digit fractions, and 1/e. Continuing previous research,
      a table of e-based ratios (e-BR) was developed. Data from 9 published experiments
      with regular and irregular signals (RS-IS) and from 9 with extraverted and
      introverted subjects (E-I) were re-analyzed. Significant numerical correlations
      were obtained, some concerning effects originally reported as nonsignificant.
      Detection (D) means all categories ("levels" of both factors) were linearly
      related, with p(D) approximately mean(5/8 + y/9) and p < .01. Cross-factor
      averaged mean products of ratio D for each time period also showed convergence (p
      < .01). The over-all mean and stability ratio of detections (SR[D], i.e., D for
      final time period/D for initial time period, gave the scaling effect 8 square
      root of 1/24:24 square root of 1/24. Response-time means and standard deviations
      for different groups in Mackie, Wylie, and Smith's 1994 sonar experiments were
      related by the derivatives of [1 - 1/e] included in the new table (p = .002).
      Although by no means specific to vigilance (or psychophysics), the numeric factor
      still seems relevant to research.

PMID- 7624223
TI  - Causality, linearity, and circularity of relations between stressful life events
      and pain experience.
AB  - The aim of this paper is to point out a methodological problem found in the 1994
      Naidoo and Pillay study on pain experience. The problem is that an equivocal
      interpretation of cause-and-effect relationships among variables can lead to
      testing of mistaken hypotheses in later researches.

PMID- 7624224
TI  - Effects of subliminally presented auditory suggestions of itching on scratching
      behavior.
AB  - This study investigated effects of masked verbal suggestions of itching,
      utilizing a design closely analogous to commercially available subliminal
      audiotapes. Students participated in 1 of 3 groups (n = 21): an experimental
      group listened to an audiotape with music masking suggestions of itching, Control
      Group 1 listened to an audiotape with music only, and Control Group 2 listened to
      suggestions of itching presented supraliminally. Dependent variables included
      both behavioral and self-report measures of itching. There was no evidence of
      influence from subliminal suggestion; however, results assessing the influence of
      supraliminally presented suggestions were mixed for self-report and behavioral
      measures.

PMID- 7624225
TI  - Children's global self-esteem predicted by body-esteem but not by weight.
AB  - Three factors of a body-esteem scale, Appearance, Weight, and Attribution, were
      inversely related to relative weight in youngster between 8 and 16 years old (243
      girls and 168 boys). Global self-esteem, however, was generally not related to
      relative weight. Nonetheless, self-esteem covaried with Appearance and
      Attribution.

PMID- 7624226
TI  - Use of energy cost and variability in stride length to assess an optimal running
      adaptation.
AB  - The aim of this study was to analyse how subjects' running adaptation was
      affected after a training overload. 14 middle-distance runners were tested before
      and after a training protocol of 15 days conducted only at one training pace. The
      efficacy of this training protocol to improve energy cost of running was observed
      only at the training pace. This improvement was correlated with a particular
      systematic variation in stride length whereas no changes in stability of stride
      length were recorded. The data were interpreted in terms of specificity of
      training for which energy cost and stability of stride length could be considered
      criteria of an optimal adaptation to the training pace.

PMID- 7624227
TI  - "Hello, I'm...".

PMID- 7624228
TI  - Emotional distress reported by women and husbands prior to a breast biopsy.
AB  - The purpose of this study was to describe the emotional distress of women (N =
      300) and husbands (N = 265) prior to the women's breast biopsy and to identify
      factors related to their levels of distress. Standardized instruments were used
      to measure social support, uncertainty, marital satisfaction, family functioning,
      concurrent stress, hopelessness, and emotional distress. Women reported
      moderately high levels of emotional distress and significantly more distress than
      their husbands. Forty-two percent of the variance in women's distress scores and
      42% of the variance in husbands' distress scores were accounted for by the
      independent variables. Concurrent stress, lower education, hopelessness, and
      uncertainty explained the most variance in women's distress, while concurrent
      stress, hopelessness, and family functioning explained the most variance in
      husbands' distress.

PMID- 7624229
TI  - Optimism and coping with a breast cancer symptom.
AB  - This study was conducted to assess whether optimism was associated with less
      delay and anxiety in seeking care for breast cancer symptoms, expectations about
      such care seeking, and the likelihood of having breast cancer. The influence of
      optimism on delay and anxiety through expectations about care seeking or
      likelihood of breast cancer was also examined. Participants (N = 135) with breast
      cancer symptoms and no history of cancer were interviewed at a surgery clinic.
      Optimism was associated with less delay and anxiety in care seeking and with
      expectations of desirable outcomes of care seeking. After controlling for
      expectations about care seeking, the relationship of optimism and anxiety became
      nonsignificant. Adjusting for differences in occupational status, the
      relationship of optimism and delay was nonsignificant. Thus, optimism may
      influence anxiety in care seeking for breast cancer symptoms through situation
      specific expectations. The influence of optimism on delay may be confounded with
      socioeconomic factors.

PMID- 7624230
TI  - Salvaging self: a grounded theory of pregnancy on crack cocaine.
AB  - A grounded theory was developed to describe how pregnant crack cocaine users
      perceived their problems and responded to them. A basic social psychological
      process, salvaging self, was identified from constant comparative analysis of in
      depth interviews with 60 pregnant or postpartum women who used crack cocaine an
      average of at least once per week in pregnancy. Salvaging self included two
      phases, facing the situation and evading harm. Participants evaluated the value,
      hope, and risk of various responses to pregnancy. Actions included strategies of
      harm reduction and stigma management aimed at reducing damage to the fetus, their
      identities as individuals and mothers, and the maternal-child relationship.
      Personal histories and social contexts influenced the salvaging process.

PMID- 7624232
TI  - Coping among spouses or significant others of persons with multiple sclerosis.
AB  - The purpose of this study was to identify coping strategies used by a sample of
      156 spouses/significant others of persons with multiple sclerosis (MS) in meeting
      the challenges of living with and/or caring for someone with MS. An additional
      purpose was to determine if differences existed among the coping strategies with
      respect to frequency of use, dependency status of the person with MS, the
      presence or absence of illness in the spouse/significant other, and the latter's
      gender and relationship to the person with MS. Low alpha coefficients were
      obtained on most of the Jalowiec Coping Scale (JCS) subscales. Subsequent factor
      analysis resulted in six factors. Two were problem focused (Planning,
      Confrontive); three were emotion focused (Ambivalence, Escape/Anger, Distancing);
      and one was problem and emotion focused combined (Accepting). The factors
      represented 31 of the 60 JCS items. Alpha coefficients were between .66 and .76.
      Significantly more problem-than emotion-focused coping dimension strategies were
      used. More coping strategies were used from the Planning. Distancing, and
      Escape/Anger dimensions when persons with MS were dependent rather than
      independent; the Distancing dimension when the spouse/significant other was also
      ill; and the Planning dimension when the spouse/significant other was a man.
      Spouses used more coping strategies from the Ambivalence and fewer from the
      Distancing and Escape/Anger dimensions than did significant others.

PMID- 7624231
TI  - Development and testing of the barriers to cessation scale.
AB  - The purpose of this research was to develop and test a measure of barriers to
      smoking cessation. Barriers, reconceptualized within the Transactional Model of
      Stress (Lazarus, 1966), reflect specific stressors associated with smoking
      cessation. The measure consists of a 19-item scale, which has been tested in
      three studies. Cronbach's alpha coefficients ranged from .81 to .87. Construct
      validity was demonstrated by correlations between barriers scores and scores on
      the Daily Hassles Scale (DeLongis, Folkman, & Lazarus, 1988). Predictive validity
      was demonstrated by findings that barriers scores significantly contributed to
      classification of abstainers versus relapsers 8 weeks after smoking cessation
      group participants quit smoking.

PMID- 7624233
TI  - Workload and environmental factors in hospital medication errors.
AB  - Nine hospital workload factors and seasonal changes in daylight and darkness were
      examined over a 5-year period in relation to nurse medication errors at a medical
      center in Anchorage, Alaska. Three workload factors, along with darkness, were
      found to be significant predictors of the risk of medication error. Errors
      increased with the number of patient days per month (OR/250 patient days = 1.61)
      and the number of shifts worked by temporary nursing staff (OR/10 shifts = 1.15);
      errors decreased with more overtime worked by permanent nursing staff members
      (OR/10 shifts = .85). Medication errors were 95% more likely in midwinter than in
      the fall, but the effect of increasing darkness was strongest; a 2-month delay
      was found between the level of darkness and the rate of errors. More than half of
      all medication errors occurred during the first 3 months of the year.

PMID- 7624234
TI  - Center as haven: findings of an urban ethnography.
AB  - In underserved, inner-city ghettos known for drug-related violence and crime,
      active participation in community life is dangerous and even life-threatening.
      This is especially true for elders burdened with the infirmities of aging and
      lacking the means to provide for alternatives to social isolation. These
      conditions can increase their risks for mental and physical ill health. In this 3
      year urban ethnography, a Philadelphia senior center that provided a haven during
      daytime hours was found to be vital to the social health of elders. In the
      center, elders exchanged fear and social isolation for companionship as a means
      to survive threats to their health and well-being. This finding suggests the need
      to understand the life exigencies of inner-city residents to provide culturally
      competent health care.

PMID- 7624235
TI  - A meta-analysis of the effects of psychoeducational care in adults with
      hypertension.
AB  - A meta-analysis of 102 studies was conducted to determine the effects of
      psychoeducational care on blood pressure (n = 89), knowledge about hypertension
      (n = 30), medication compliance (n = 23), weight (n = 16), compliance with health
      care appointments (n = 11), and anxiety (n = 6). Small- to medium-sized
      statistically significant beneficial effects were found on blood pressure for
      several types of psychoeducational care (education only, behavioral monitoring
      only, and relaxation). However, in the better controlled studies, the effect of
      relaxation on blood pressure was much smaller and not statistically significant.
      Statistically significant large treatment effects were obtained on knowledge,
      medication compliance, and compliance with health care appointments. Threats to
      validity limited conclusions about the effects of psychoeducational care on the
      weight and anxiety of adults with hypertension.

PMID- 7624236
TI  - Job satisfaction and turnover among nurses: integrating research findings across
      studies.
AB  - A meta-analytic study investigated the causal relationships among job
      satisfaction, behavioral intentions, and nurse turnover behavior. A theoretical
      model was proposed in which behavioral intentions were viewed as a direct
      antecedent to turnover behavior. Job satisfaction was expected to be indirectly
      related to turnover by virtue of the mediating role of behavioral intentions.
      Consistent with these expectations, a strong positive relationship was indicated
      between behavioral intentions and turnover; a strong negative relationship
      between job satisfaction and behavioral intentions; and a small negative
      relationship between job satisfaction and turnover. The results of the modifier
      analysis suggested that effect sizes are fairly robust to differences in study
      designs, response rates, and methods of measuring job satisfaction, but the
      manner in which behavioral intentions were operationalized appeared to moderate
      the relationship between behavioral intentions and turnover and job satisfaction.
      Of variables related to nursing job satisfaction, work content and work
      environment had a stronger relationship with job satisfaction than economic or
      individual difference variables.

PMID- 7624237
TI  - Under mined.

PMID- 7624238
TI  - Widening horizons.

PMID- 7624239
TI  - Back in touch.

PMID- 7624240
TI  - Stobhill mourns.

PMID- 7624242
TI  - Breaking boundaries.

PMID- 7624241
TI  - Taking counsel.

PMID- 7624243
TI  - Safety measures.

PMID- 7624244
TI  - Bench marks.

PMID- 7624245
TI  - Central support.

PMID- 7624246
TI  - Taking notes.

PMID- 7624247
TI  - Implications of client-centred counselling for nursing practice.
AB  - The idea that counselling should be incorporated into nursing has been discussed
      widely in nursing literature. The type of counselling that is most often
      recommended is 'client-centred'. This term refers to a specific style of
      counselling based on a particular view of people. This paper explores the concept
      of client-centred counselling and argues that the client-centred approach to
      counselling is both limited and limiting.

PMID- 7624248
TI  - Managing manual handling in clinical situations.
AB  - The extent to which nurse managers at site level are now responsible for the
      development and management of systems of work designed to reduce the risk to
      nurses from patient handling is not always clear. This paper, and a second due to
      appear next month, will draw attention to the practical implications of the
      regulations and how they affect the management roles of nurse managers at site
      level. Their interpretation does, however, depend on an understanding of its
      legal status and thus its historical and political links.

PMID- 7624249
TI  - Valuing the unseen emotional labour of nursing.
AB  - This paper argues that comforting, listening, being reassuring and showing
      sympathy are important nursing skills that are vital to a patients' well-being
      and, as such, should be both valued and remunerated. The author also argues that
      the invisibility of these skills has been compounded by the NHS and Community
      Care Act 1990. This has meant that long-term care is being transferred into the
      hands of the private and voluntary sectors and informal carers. As an alternative
      to residential care, many social services departments now use the home care
      services of not-for-profit care agencies who employ 'ordinary' people to enable
      those needing long-term care to remain in their own home. Such workers are often
      paid in a way that does not remunerate the emotional element of their labour.

PMID- 7624250
TI  - Job satisfaction and morale of nurses in NHS trusts.
AB  - In April 1991 the Daphne Heald Research Unit at the Royal College of Nursing
      (RCN) started a three-year research project to assess the job satisfaction of
      nurses working in the community. This took place against a backdrop of
      considerable change in the organisation and funding of community health care.
      Initially four NHS Trusts participated, one withdrew after the first year. A
      measure of job satisfaction was administered to the entire community nursing and
      practice nursing workforce in each area. The response rate varied from 74% (year
      1) to 54% (year 2). Differences in satisfaction were detected between trusts,
      different groups of nurse and over time. Some nurses added comments to their
      questionnaire, voicing concerns over uncertainty, paperwork and a perceived
      change in ethos within their organisations. Trust managers interviewed as part of
      the study spoke of their strategies for local implementation of the national
      changes.

PMID- 7624251
TI  - Grinding down.

PMID- 7624252
TI  - Green matters.

PMID- 7624254
TI  - Stoma nursing. Jobs and training in Europe.

PMID- 7624253
TI  - Ginny's swansong?

PMID- 7624255
TI  - Cognitive therapy: a well-thought-out strategy.
AB  - Designing strategies for nursing care is a complex process. Carefully evaluating
      the nature of the client's problem is a beginning step in the eventual design of
      a strategy. In this case a careful review of the problem of depression led to the
      discovery of faulty reasoning mechanisms used by clients who experience
      depressive episodes. Once the theoretical roots of the problem become clear, the
      design of the strategy is a natural progression. The success or failure of a
      strategy is measured by research. The author uses selective examples to describe
      how various aspects of cognitive therapy can be incorporated into the client's
      plan of care.

PMID- 7624256
TI  - A glance back in time, 1968. The emerging health occupations.
AB  - As individuals, we have history, the present, and the future. Each of us is the
      embodiment of these experiences. In order to understand nursing today and its
      future paths, our history needs exploration. In an effort to provide the reader a
      perspective on where we were, how far we have traveled, or, in some instances,
      how little has changed, we reprint this article from Nursing Forum, 1968, 7(1),87
      97.

PMID- 7624257
TI  - A nurse is a nurse is a nurse.

PMID- 7624258
TI  - Exploring nursing outcomes for health promotion.
AB  - The author examines nursing outcomes in relation to the aspect of nursing that
      deals with health promotion. The focus is on identifying factors that influence
      nursing outcomes and outcome selection, health promotion in the context of
      today's nursing practice, and the importance of nurses articulating their unique
      contribution to health promotion. The author also discusses measurement
      challenges inherent in outcome evaluation, and suggests future directions for
      enhancing outcome evaluation in health promotion.

PMID- 7624259
TI  - Lamotrigine.
AB  - Lamotrigine is a novel antiepileptic that, although its mechanism is not
      completely understood, appears to affect voltage-activated sodium channels,
      resulting in inhibition of the presynaptic release of the excitatory
      neurotransmitter glutamate. It is well absorbed after oral administration. Its
      route of elimination is hepatic glucuronidation, which is susceptible to both
      hepatic microsomal enzyme-inducing and -inhibiting agents. In clinical trials
      lamotrigine was effective as add-on therapy for refractory partial seizures in
      adults. Small trials suggest the feasibility of monotherapy, but further
      controlled trials are warranted to support this practice. Additional data
      indicate the utility of lamotrigine for generalized seizures. Reported side
      effects are rash, nausea, vomiting, blurred vision, diplopia, and vision
      abnormalities. Lamotrigine appears to be an attractive alternative to currently
      available antiepileptics.

PMID- 7624260
TI  - Renal function and methotrexate clearance in children with newly diagnosed
      leukemia.
AB  - STUDY OBJECTIVES: To determine whether glomerular filtration rate (GFR) changes
      during induction chemotherapy in children with leukemia, and to examine GFR as a
      determinant of pharmacokinetic variability of methotrexate clearance. DESIGN:
      Prospective, unblinded observational study in consecutive patients. SETTING: A
      research hospital. PATIENTS: Thirty-eight children newly diagnosed with acute
      lymphoblastic leukemia. INTERVENTIONS: The patients received either high-dose
      methotrexate 1 g/m2 intravenously over 24 hours or low-dose methotrexate 30 mg/m2
      orally every 6 hours for six doses; both regimens were followed by an intensive
      six-drug chemotherapy regimen given over 6 weeks. Glomerular filtration rate was
      determined in each subject before and at the conclusion of induction therapy.
      MEASUREMENTS AND MAIN RESULTS: The GFR was determined from 99mTc-DTPA serum
      clearance in all patients, and methotrexate clearance was estimated from serial
      serum concentrations in 18 of these children who received high-dose methotrexate.
      Median values for GFR at diagnosis (131 ml/min/1.73 m2) and after induction
      therapy (120 ml/min/1.73 m2) were not significantly different (p = 0.26) but were
      highly variable (range 49-274 ml/min/1.73 m2). Body size, age, and serum
      creatinine were correlated significantly with GFR at diagnosis. Amphotericin B
      therapy (6 patients) significantly decreased GFR (p = 0.046) without a
      corresponding increase in serum creatinine. Methotrexate clearance (58-155
      ml/min/m2) was significantly (p = 0.007) correlated with GFR, but GFR accounted
      for only 37% of the variability of methotrexate clearance. CONCLUSIONS: The GFR
      was normal but highly variable in these children with leukemia and was
      significantly altered by amphotericin. Our results explain little of the
      intersubject variability in methotrexate clearance.

PMID- 7624261
TI  - Lymphocyte beta 2-receptor activity, metoprolol kinetics, and response to
      metoprolol in hypertensive black men.
AB  - STUDY OBJECTIVES: To evaluate whether variability in S-metoprolol kinetics and
      lymphocyte beta 2-receptor-mediated cyclic adenosine monophosphate (cAMP)
      accumulation is related to the variability in antihypertensive response to
      metoprolol of black men. DESIGN: Prospective, unblinded study. SETTING:
      University-based preventive medicine clinic. PATIENTS: Twelve hypertensive black
      men. MEASUREMENTS AND MAIN RESULTS: Ambulatory blood pressure was measured over
      24 hours before and after metoprolol administration. Ex vivo responsiveness of
      lymphocyte beta 2-receptors to isoproterenol was established for each subject
      before initiating metoprolol therapy. Plasma samples were collected over 12 hours
      at the conclusion of the study, from which metoprolol enantiomer concentrations
      were determined by chiral high-performance liquid chromatography, and kinetic
      values were calculated. The 24-hour ambulatory blood pressure responses to
      metoprolol were highly variable, with systolic blood pressure responses ranging
      from -13 to +33 mm Hg and diastolic blood pressure responses ranging from -15 to
      +15 mm Hg. There was a significant relationship between the metoprolol-induced
      change in systolic blood pressure and the maximum lymphocyte beta 2-receptor cAMP
      production (y = 0.47x-7.79; r2 = 0.49, p < 0.05) such that those with the highest
      maximum cAMP production had the greatest blood pressure increases during
      metoprolol therapy. There was no relationship between S-metoprolol concentration
      and blood pressure response. Mean oral clearance values for S- and R-metoprolol
      were 1320 and 2346 ml/minute, respectively. CONCLUSIONS: Lymphocyte beta 2
      receptor data suggest that individuals most responsive to beta-receptor
      stimulation may be at greatest risk of blood pressure elevation during beta 2
      receptor blockade. The metoprolol enantiomer kinetic data are markedly different
      from previously published data and may represent racial differences in
      pharmacokinetics.

PMID- 7624262
TI  - Comparative evaluation of the hemodynamic effects of oral cimetidine, ranitidine,
      and famotidine as determined by echocardiography.
AB  - STUDY OBJECTIVE: To evaluate the influence of cimetidine, ranitidine, famotidine,
      and placebo on cardiac performance as determined by echocardiography. DESIGN:
      Randomized, four-way crossover trial. SETTING: Echocardiography laboratory at a
      university hospital. PARTICIPANTS: Twelve healthy volunteers. INTERVENTIONS:
      Volunteers received oral treatment with placebo, cimetidine 800 mg, ranitidine
      300 mg, or famotidine 40 mg once/day for 7 days. MEASUREMENTS AND MAIN RESULTS:
      On the seventh day of each study phase, 2 hours after administration of the final
      dose, each subject underwent cardiac echocardiography and Doppler flow studies.
      No significant differences were detected in ejection fraction, peak flow
      velocity, or percentage fractional shortening among the treatment phases. A large
      degree of variability in ejection fraction was observed, with some subjects
      experiencing marked decreases. CONCLUSION: The histamine-2 (H2)-receptor
      antagonists had no effect on the hemodynamic variables as determined by
      echocardiography. The variability in the hemodynamic response may in part explain
      the conflicting results reported in the literature. It also raises the question
      as to whether certain individuals are more sensitive to the potential cardiac
      effects of H2-receptor antagonists.

PMID- 7624263
TI  - Effect of erythromycin on ethanol's pharmacokinetics and perception of
      intoxication.
AB  - STUDY OBJECTIVE: To determine the effect of erythromycin on ethanol's
      pharmacokinetics and perception of intoxication. DESIGN: Double-blind,
      randomized, placebo-controlled, crossover study. SETTING: A clinical research
      center. PARTICIPANTS: Ten healthy volunteers. INTERVENTIONS: Erythromycin base
      500 mg or identical placebo was administered 3 times/day for 7 days. On day 8,
      ethanol 0.8 g/kg was administered by mouth concurrently with erythromycin or
      placebo. A 2-week washout period was allowed between each treatment arm.
      MEASUREMENTS AND MAIN RESULTS: Twelve blood samples were obtained over a 12-hour
      period to determine ethanol concentrations. Perception of intoxication was
      determined at each time point using a 10-cm visual analog scale. Ethanol
      concentrations were determined using a gas chromatographic method. Mean +/- SD
      ethanol pharmacokinetics for erythromycin versus placebo were time to peak
      ethanol plasma concentrations 1.1 +/- 0.4 hours versus 1.3 +/- 0.3 hours, peak
      ethanol concentrations 118 +/- 18 mg/dl versus 114 +/- 27 mg/dl, ethanol oral
      clearance (CL/F) 2.9 +/- 0.8 ml/min/kg versus 3.4 +/- 2.2 ml/min/kg, and area
      under the curve 481 +/- 104 mg.hour/dl versus 465 +/- 132 mg.hour/dl (p > 0.05).
      The blood ethanol concentrations and perception of intoxication scores on a
      visual analog scale were well correlated (r2 = 0.78, p < 0.01). Mean +/- SD areas
      under the effect versus time curve were 35.1 +/- 20.7 cm/hour and 31.5 +/- 18.2
      cm/hour for erythromycin and placebo, respectively (p > 0.05). CONCLUSION: Oral
      erythromycin base 1500 mg/day compared with placebo does not alter ethanol's
      pharmacokinetics or perception of intoxication in healthy volunteers.

PMID- 7624264
TI  - The effect of three different ranitidine dosage regimens on reducing gastric
      acidity and volume in ambulatory surgical patients.
AB  - STUDY OBJECTIVE: To evaluate three different preoperative oral dosing regimens of
      ranitidine in ambulatory patients who had significant risk of aspiration
      pneumonitis (gastric pH < or = 2.5 or volume > or = 25 ml at intubation or
      extubation). DESIGN: Double-blind, placebo-controlled, randomized trial. SETTING:
      St. Francis Hospital of Buffalo, New York. PATIENTS: Two hundred seventy-one
      ambulatory patients about to undergo a surgical procedure under general
      anesthesia, of whom 241 (89%) completed the trial and were considered evaluable.
      INTERVENTIONS: Patients were randomly assigned to receive one of four regimens
      administered orally before surgery: placebo at bedtime the night before and in
      the morning on the day of surgery; ranitidine 150 mg at bedtime and in the
      morning; ranitidine 150 mg at bedtime and placebo in the morning; or ranitidine
      300 mg at bedtime and placebo in the morning. MEASUREMENTS AND MAIN RESULTS:
      Patients who received ranitidine 150 mg twice/day, ranitidine 150 mg at bedtime,
      or ranitidine 300 mg at bedtime had a significantly (p < 0.05) lower frequency of
      a gastric pH 2.5 or below at intubation or extubation than those taking placebo
      twice/day (3%, 45%, and 31%, respectively, vs 86%). In addition, gastric volume
      at intubation or extubation was 25 ml or above in significantly fewer patients
      receiving ranitidine 150 mg at bedtime than placebo (37% vs 13%, p < 0.05).
      Overall, the number of patients with risk factors for aspiration pneumonitis was
      significantly lower with ranitidine 150 mg twice/day (20%), ranitidine 150 mg at
      bedtime (48%), and ranitidine 300 mg at bedtime (35%) than placebo (86%) (p <
      0.001), and significantly lower with ranitidine 150 mg twice/day than ranitidine
      150 mg at bedtime (p < 0.05). CONCLUSIONS: Ranitidine 150 mg twice/day
      preoperatively reduced to the greatest degree the percentage of patients who
      developed significant risk factors for aspiration pneumonitis after surgery under
      general anesthesia.

PMID- 7624265
TI  - The risk of sulfasalazine- and mesalazine-associated blood disorders.
AB  - Sulfasalazine (SASP) has often been reported to cause serious blood disorders,
      particularly agranulocytosis; however, little quantitative information is
      available to estimate the risk or to identify possible modifiers of the risk. We
      used comprehensive clinical information recorded on office computers by selected
      general practitioners in Britain to conduct a follow-up study of some 10,000
      users of SASP and some 4000 users of mesalazine to estimate the risk of blood
      disorders associated with these drugs. Overall, the frequency of blood disorders
      attributable to SASP was 27/10,332 (2.6/1000 users). The risk for SASP users who
      were treated for arthritic disorders (6.1/1000 users) was some 10 times higher
      than that for users who were treated for inflammatory bowel disease (0.6/1000
      users). There were no cases of blood disorders in users of mesalazine.

PMID- 7624266
TI  - Toxicology and management of acute drug ingestions in adults.
AB  - We reviewed the current literature on the toxicology and management of acute drug
      ingestions in adults after a MEDLINE search of English-language journal articles.
      Information on toxicology was also acquired from relevant textbooks. Present
      statistics were gathered through information from the U.S. Department of Health
      and Human Services and the American Association of Poison Control Centers. All
      patients with acute drug ingestions should be treated with supportive care
      initially, and when stabilized, undergo active removal of the ingested substance,
      based on the diagnostic and prognostic assessment. Identification of the ingested
      substance may prove useful in some instances when specific therapy or antidotes
      are indicated.

PMID- 7624267
TI  - National survey of once-daily dosing of aminoglycoside antibiotics.
AB  - To evaluate the scope of once-daily dosing of intravenous aminoglycoside
      antibiotics, a questionnaire was designed and mailed to a random sample of
      pharmacy directors at 500 acute care hospitals in the United States. The response
      rate was 68.4%. Nineteen percent of the respondents reported use of once-daily
      dosing of aminoglycosides. Affiliation with a pharmacy residency program and the
      presence of a pharmacokinetic consultation service by the pharmacy department
      were associated with this practice (p < 0.05). No other statistically significant
      differences were found. Reported indications, contraindications, and dosing were
      consistent with those found in the literature. The profession of pharmacy, as
      demonstrated by pharmacy residency programs and pharmacokinetic consultation
      services, appears to have been instrumental in implementing this method of dosing
      aminoglycosides.

PMID- 7624268
TI  - Current patterns of prescribing and administering morphine in trauma patients.
AB  - We attempted to characterize the current prescribing practices and administration
      patterns for intravenous intermittent morphine in trauma patients in a
      multicenter, open prospective, observational study. The subjects were 141
      patients admitted to the surgical intensive care units (ICU) of five United
      States trauma centers within 12 hours of injury who received intermittent
      intravenous morphine for pain relief. The study was conducted from April 15,
      1992, to February 15, 1993. Data obtained during the first 32 hours of the ICU
      stay included morphine regimen, doses administered, and time between doses. One
      hundred sixty-one orders were prescribed by surgeons. The most frequently ordered
      dose was 2-4 mg and the most frequently ordered interval was every hour as
      necessary. There was no relationship between the severity of injury and the
      minimum dose ordered. During the 492 nursing shifts studied, 1257 doses were
      administered. Of these, 44% were at or below the minimum amount prescribed by the
      surgeons. Thirty-three percent of the patients received a dose at an interval of
      more than 3 hours. We concluded that small amounts of narcotic analgesics are
      given to severely injured patients, and amount ordered is not affected by the
      severity of injury.

PMID- 7624269
TI  - Pharmacist-managed aminoglycoside therapy in combination with a beta-lactam agent
      in the treatment of nosocomial pneumonia in critically ill patients.
AB  - We attempted to determine the outcome of treatment with aminoglycosides, dosed
      pharmacokinetically using traditional strategies, in combination with synergistic
      antibiotics in the management of nosocomial pneumonia in critically ill patients
      over a 1-year period. Twenty-three adults cared for in an intensive care unit
      received an aminoglycoside dosed by a pharmacist plus a beta-lactam antibiotic.
      Of these, 21 experienced clinical cure of the disease and 2 died of unrelated
      complications. No treatment failures were encountered. Therapy with
      aminoglycosides, dosed by traditional pharmacokinetic methods, in combination
      with synergistic antimicrobials, was effective in managing nosocomial pneumonia
      in this nontertiary care regional referral center.

PMID- 7624270
TI  - A computerized system to improve documentation and reporting of pharmacists'
      clinical interventions, cost savings, and workload activities.
AB  - A major factor in delivering patient care is documenting activities by
      pharmacists. This documentation is not only essential to sustain existing
      programs but necessary to justify future growth of resources. A computerized
      documentation system for clinical interventions and workload activities was
      developed in a 340-bed university teaching hospital. With the expansion of its
      pharmaceutical care model, the department reworked its distribution process to
      allocate more pharmacist time for patient care. Manual documentation of these
      services, however, soon was identified as an obstacle. A software program was
      developed to alleviate the problems inherent with manual documentation. This
      "user-friendly" program tracks clinical recommendations and interventions by
      pharmacists, and calculates cost savings/avoidance. It also facilitates monthly
      and annual reporting for department managers.

PMID- 7624271
TI  - Variable disposition of ciprofloxacin in critically ill patients undergoing
      continuous arteriovenous hemodiafiltration.
AB  - Continuous arteriovenous hemodiafiltration (CAVHD) is being used increasingly in
      critically ill patients with acute renal failure (ARF). We prospectively
      evaluated extracorporeal and total systemic clearances (ClCAVHD and Cls) of
      ciprofloxacin during CAVHD in four patients with severe ARF to assess the
      adequacy of drug dosing. Ciprofloxacin serum and ultrafiltrate concentrations
      were measured by high-performance liquid chromatography. The ClCAVHD accounted
      for approximately 5.9% (range 2.8-11.6%) of Cls of ciprofloxacin. However, large
      variability in serum concentrations was observed with the normally recommended
      dose of 400 mg/day, and doses of up to 800 mg/day were required to maintain
      concentrations suitable for treatment of serious infections. High daily doses of
      ciprofloxacin required in these patients are likely related to altered
      pharmacokinetics in serious illness as well as to the increased extracorporeal
      clearance during CAVHD. Clinical studies to define appropriate dosing
      recommendations for ciprofloxacin during CAVHD are necessary to guide clinicians
      in optimum drug use.

PMID- 7624272
TI  - Accuracy and reliability of dosing equations to individualize theophylline
      treatment of apnea of prematurity.
AB  - Apnea of prematurity is associated with high morbidity and mortality. Treatment
      generally includes supplemental oxygen and theophylline or caffeine. The half
      life of theophylline is prolonged in newborns because of their immature
      cytochrome P-450 system, and there is considerable variation in the drug's
      metabolism in infants. We compared the accuracy, precision, and reliability of
      two equations that use postnatal age (PNA) to determine a maintenance dosage of
      theophylline with a standard maintenance dosage (SMD) that produced a steady
      state serum theophylline concentration (STC) of 8 micrograms/ml for apnea of
      prematurity in 46 infants less than 34 weeks' gestational age (GA) and less than
      36 weeks' postconceptional age (PCA). The two equations were mg/kg/day = [(0.2 x
      PNA in wks) + 5], and mg/kg/day = [(0.3 x PNA in wks) + 8]. Their reliability to
      predict the SMD was determined by correlation analysis. The precision and
      accuracy with which they predicted SMD were determined and analyzed by chi 2. The
      SMD did not correlate with the maintenance dosages calculated by equations 1 and
      2 (r = 0.296 and 0.296, p > 0.05 in both cases). Multiple linear regression of
      SMD versus GA, PNA, and PCA was not significant (r = 0.33, p = 0.32). After
      stratifying data based on GA and performing correlation analysis of SMD versus
      PNA, a weak but significant correlation (r = 0.42, p = 0.517) was found for
      infants with GA between 31 and 34 weeks. Poor correlation was found between SMD
      versus PNA for infants 27-30 weeks' GA. Two new equations of the best fit line
      were generated using the same data.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7624273
TI  - Flucytosine dosing in an obese patient with extrameningeal cryptococcal
      infection.
AB  - A 31-year-old, obese woman with extrameningeal cryptococcal disease was admitted
      to the Medical College of Virginia for antifungal therapy. Various physiologic
      variables influence flucytosine pharmacokinetics, and there are no guidelines for
      dosing the agent in obese patients. This patient received a dosage based on her
      ideal body weight, and serum drug concentrations were monitored. She recovered
      without sequelae.

PMID- 7624275
TI  - Toxic epidermal necrolysis after initiation of felbamate therapy.
AB  - A 33-year-old woman with a 13-year history of partial complex seizures
      experienced toxic epidermal necrolysis requiring management in a regional burn
      treatment center after 16 days of single-agent treatment for epilepsy with
      felbamate 3600 mg/day. Within 24 hours the target lesions involved 45% of her
      total body surface area. They coalesced and progressed to exfoliation involving
      the mucosa and the conjunctiva. The patient was hospitalized for 25 days. Reports
      in the literature describe life-threatening rashes after treatment with felbamate
      in combination with other anticonvulsant agents. We believe this to be the first
      reported case of felbamate-induced toxic epidermal necrolysis induced by single
      agent therapy. Although felbamate provides many advantages as an anticonvulsant,
      its structure can be arranged to a conformation in space similar to that of
      hydantoins and barbiturates, and thus warrants careful patient monitoring for
      life-threatening rashes.

PMID- 7624274
TI  - Prolonged neuromuscular blockade in two critically ill patients treated with
      atracurium.
AB  - Recent literature suggests that the risk of prolonged neuromuscular blockade
      associated with atracurium compared with other nondepolarizing neuromuscular
      blocking agents may be minimal. Two patients experienced prolonged weakness
      associated with the administration of atracurium. Both received atracurium 0.5
      0.7 mg/kg/hour in combination with methylprednisolone 500-600 mg/day.
      Electromyographic results and creatine kinase levels were suggestive of muscular
      weakness in both patients. Despite high-dose corticosteroid therapy, the
      electromyographic evidence supporting prolonged weakness did not suggest typical
      corticosteroid myopathy. Although some clinicians advocate routine administration
      of atracurium in critically ill patients due to the relative lack of reports of
      prolonged weakness, this may be premature. Although there are fewer reports of
      atracurium-associated prolonged weakness compared with pancuronium and
      vecuronium, the patients we describe suggest that it may occur.

PMID- 7624276
TI  - Pubertal and psychosocial development implications for pediatricians.

PMID- 7624277
TI  - Neonatal seizures.

PMID- 7624278
TI  - Peptic ulcer disease in children.

PMID- 7624279
TI  - Special considerations in the use of glucocorticoids in children.
AB  - GCs are used commonly for the treatment of various inflammatory and autoimmune
      diseases. Although potent and generally effective, they are not without risks for
      producing serious adverse effects, especially when used in high doses for
      prolonged periods of time. Thus, the clinician must balance the therapeutic
      effects of GCs with their risks for adverse effects; using the lowest possible
      effective GC doses as well as maximizing other therapeutic modalities are means
      by which this goal can be achieved. Early recognition and appropriate management
      are other methods to minimize GC-induced adverse effects. Maximization of
      therapy, early recognition, and appropriate management of adverse effects can
      minimize the potential severe complications of GC therapy.

PMID- 7624280
TI  - Cerebral abscess and congenital heart disease.

PMID- 7624281
TI  - Poststreptococcal acute glomerulonephritis.

PMID- 7624282
TI  - Properties of a blood-meal-induced midgut lectin from the tsetse fly Glossina
      morsitans.
AB  - The properties of a blood-meal-induced lectin (agglutinin) from the midgut of
      Glossina morsitans capable of agglutinating Trypanosoma brucei were studied in
      vitro. The midgut homogenate from flies that had been fed twice had the highest
      agglutination activity, followed by that from the once-fed flies and that from
      the unfed insects. As compared with the bloodstream-form trypanosomes, a much
      lower concentration of the midgut homogenate was required for agglutination of
      the procyclic parasites. Furthermore, the agglutination process was specifically
      inhibited by D-glucosamine. Soybean trypsin inhibitor abrogated agglutination of
      the bloodstream-form parasites, whereas the procyclics were unaffected. The
      agglutination process was temperature-sensitive, with little activity being
      evident between 4 degrees and 15 degrees C. Similarly, heating the midguts to 60
      degrees-100 degrees C led to loss of activity. When the midgut homogenate was
      separated by anion-exchange chromatography, the agglutination activity co-eluted
      with trypsin activity at approximately 50% NaCl. These results suggest a very
      close relationship between midgut trypsin-like enzyme and the agglutinin. Since
      successful agglutination of bloodstream-form trypanosomes requires protease
      activity, it may be that the enzyme cleaves off some surface molecules on the
      parasite surface, thus exposing the lectin-binding sites.

PMID- 7624283
TI  - Purification and characterization of a midgut lectin-trypsin complex from the
      tsetse fly Glossina longipennis.
AB  - A blood-meal-induced lectin (agglutinin) with proteolytic activity was isolated
      from midgut extracts of Glossina longipennis by a two-step procedure involving
      anion-exchange chromatography. It is a glycoprotein [native molecular weight
      (M(r) 61,000 +/- 3000 da) composed of two noncovalently-linked subunits
      designated alpha (M(r), approximately 27,000 da) and beta (M(r), approximately
      33,000 da). The trypsin activity and the glycosyl residues were present on the
      alpha- and beta-subunits, respectively. The native protein was capable of
      agglutinating both bloodstream-form and procyclic trypanosomes as well as rabbit
      red blood cells. This activity was strongly inhibited by D-glucosamine and weakly
      inhibited by N-acetyl-D-glucosamine. Similarly, soybean trypsin inhibitor
      abrogated agglutination of bloodstream-form parasites, whereas the procyclics
      were unaffected. The agglutination activity was sensitive to temperatures above
      40 degrees C but was unaffected by chelators of metal ions. Antibodies raised
      against the protein were used in immunoblotting experiments to show the presence
      of a similar protein in several members of the Glossina species. However, no
      cross-reactivity was detected with midgut extracts prepared from sandflies,
      mosquitoes, or stable flies. It is proposed that this molecule might play an
      important role in differentiation of bloodstream-form trypanosomes into procyclic
      (midgut) forms.

PMID- 7624284
TI  - Identification of intra- and interspecific Leishmania genetic polymorphisms by
      arbitrary primed polymerase chain reactions and use of polymorphic DNA to
      identify differentially regulated genes.
AB  - Arbitrary primed polymerase chain reactions (AP-PCR) were used to amplify
      different polymorphic genomic DNA fragments from various Old World Leishmania
      species. Using four 10-mer AP primers, geographic isolates of L. donovani and
      various Old World species of Leishmania could be readily distinguished from one
      another by the pattern of amplified DNA products. Our studies confirmed two
      important characteristics of AP-PCR: its abilities to amplify a consistent
      pattern of DNA fragments from the genomes of different isolates of a single
      species and to identify genetic polymorphisms between the species isolates. We
      selected three polymorphic DNA fragments that differentiate L. donovani
      geographic isolates for further analysis. Sequence analysis of the clones derived
      from these three polymorphic fragments revealed eight unique sequences. Six of
      eight unique clones hybridized to distinct RNAs upon Northern-blot analysis.
      Three of these six clones hybridized to RNAs expressed differentially in in vitro
      grown L. donovani pro- and "amastigotes." One of the differentially expressed
      clones, LdE-6-1, exhibited restriction length polymorphisms that distinguished L.
      donovani from L. tropica and L. major. Comparative Northern blotting revealed
      that LdE-6-1 was differentially expressed in some members of the L. donovani
      species complex but not in L. major or L. tropica. These results demonstrate that
      AP-PCR can be used to generate products reflecting particular genes in organisms
      with low-complexity genomes.

PMID- 7624285
TI  - Glucantime susceptibility of Leishmania promastigotes under variable growth
      conditions.
AB  - Growth inhibition of Leishmania promastigotes by glucantime was compared in three
      different media. Glucantime inhibited the growth of Leishmania cultured in
      complex medium but did not affect parasite growth when added to cells cultured in
      defined or semi-defined media. Supplementation of the complex medium with
      biopterin partially reversed the glucantime effect in sensitive strains, although
      the addition of folic acid or oleic acid did not alter the activity of
      glucantime. Differences in fatty acid composition were observed between strains
      showing different degrees of glucantime susceptibility.

PMID- 7624286
TI  - A pilot study on the efficacy of epiroprim against developmental stages of
      Toxoplasma gondii and Pneumocystis carinii in animal models.
AB  - The new bacteriocidal drug epiroprim (Ro-11-8958) was tested (alone or in
      combination with dapsone) on its efficacy against Toxoplasma gondii and
      Pneumocystis carinii in their hosts: laboratory mice and/or nude mice/rats, and
      was compared to the curative effects of the recent drugs of choice. The
      experiments clearly pointed out that epiroprim has significant effects on the
      reduction of both parasites when given alone. In combination with dapsone
      epiroprim led to a complete cure of toxoplasmosis in mice. This finding is of
      some importance for AIDS patients mostly suffering from bacteriosis and
      parasitosis at the same time.

PMID- 7624287
TI  - In vivo metabolism of aminopyrine by the larvae of the helminth Heligmosomoides
      polygyrus.
AB  - The in vivo N-dealkylation of [13C-2]-labeled aminopyrine by the L1-L2 larvae of
      Heligmosomoides polygyrus was demonstrated by the use of a sensitive gas
      chromatography-mass spectrometry method. This is the first evidence for the
      possible existence of a cytochrome P-450-dependent activity in helminths.

PMID- 7624288
TI  - Malaria diagnosis: identification of an anti-40-kDa polypeptide antibody response
      associated with active or recent infection and study of the IgG/IgM ratio of
      antibodies to blood-stage Plasmodium falciparum antigens.
AB  - The need for an alternative methodology to assess disease activity in the case of
      malaria led us to evaluate the usefulness of studying the humoral immune response
      to establish the diagnosis of past or recent malaria. For this purpose, we
      analyzed sera from 439 individuals living in endemic areas of the Amazon region
      (Ariquemes, Rondonia). Individuals were classified according to the number and
      the date of past crises. The enzyme-linked immunosorbent assay (ELISA) was
      performed to evaluate the IgG/IgM ratio so as to discriminate acute or recent
      malaria from past infections against crude and defined (SPF70) Plasmodium
      falciparum asexual blood-stage antigens. We also analyzed the humoral immune
      response against components presented in crude P. falciparum antigen by the
      immunoblot technique. Use of the IgG/IgM ratio values did not allow us to
      differentiate acute from past infections. However, when we analyzed the humoral
      immune response to parasite components, we were capable of identifying a
      polypeptide with a molecular weight ranging up to 40 kDa, which was recognized by
      all parasitized polyinfected individuals studied but not by individuals with
      negative thick blood smears. In view of these data, we conclude that the 40-kDa
      polypeptide may represent a powerful tool in the diagnosis of acute malaria,
      mainly for screening blood donors in endemic areas.

PMID- 7624289
TI  - rRNA gene sequence heterogeneity among Toxoplasma gondii strains.

PMID- 7624290
TI  - Evaluation of serum chemistry values associated with avian malaria infections in
      African black-footed penguins (Spheniscus demersus).
AB  - The value profiles of 5 intracellular enzymes, 15 metabolites (with 2 associated
      ratios), and 3 electrolytes were monitored over time in 9 captive-reared African
      black-footed penguins (Spheniscus demersus) with different avian malaria clinical
      status: uninfected, subclinically infected, and clinically infected with fatal
      outcome. Fatal infections were caused by Plasmodium relictum. Numerous schizonts
      were visible in the lungs, liver, spleen, and interstitial tissue of the kidneys.
      The reference ranges of 23 serum clinical chemistry parameters and 2 ratios were
      established for S. demersus. The mean values obtained for 8 of 23 parameters of
      the infected penguins were significantly different from those recorded for the
      uninfected birds, indicating impaired renal function, hepatic dysfunction, and
      nonspecific tissue damage related to the infestation with exoerythrocytic
      schizonts. Analysis of sensitivity, specificity, and negative and positive
      predictive values (PPVs) showed that gamma-glutamyltranspeptidase (GGTP), alanine
      aminotransferase (ALT), and creatinine reached PPVs and a specificity over 57%
      for avian malaria infections in penguins. Creatinine, ALT, and GGTP values should
      be consulted in evaluation of the clinical malaria status of S. demersus.

PMID- 7624291
TI  - Identification of Entamoeba histolytica intracellular phospholipase A and
      lysophospholipase L1 activities.
AB  - Entamoeba histolytica phospholipase A and lysophospholipase activities from a
      vesicular subcellular fraction (P30) were analyzed. The products, obtained using
      specific substrates labeled with 14C or 3H, indicated the presence of
      phospholipase A1 and A2 as well as lysophospholipase L1 activities. The enzymes
      detected could participate in phospholipid metabolism and the alkaline
      phospholipase A2 may contribute to E. histolytica cytopathogenicity.

PMID- 7624292
TI  - Study of the inter- and intraspecific variation of Eimeria spp. from the rabbit
      using random amplified polymorphic DNA.
AB  - A genetic polymorphism study was performed in coccidia from the rabbit. A
      comparative analysis of the RAPD (random amplified polymorphic DNA)-generated
      fingerprints, using 11 arbitrary primers, was carried out (1) in nine Eimeria
      species (E. intestinalis, E. magna, E. piriformis, E. flavescens, E. vejdovskyi,
      E. coecicola, E. perforans, E. exigua, and E. media) and (2) in two strains of E.
      intestinalis and four strains of E. media originating from different geographic
      areas. For each of these four strains of E. media, three lines deriving from the
      multiplication of a single oocyst were compared. All the primers tested yielded
      about ten amplified fragments. The profiles obtained differed considerably
      according to the species; thus, it was not possible to establish a phylogeny. On
      the other hand, species-specific fingerprints were observed, showing that RAPD
      assays might be useful for diagnosis. In E. media, analysis of the RAPD products
      showed weak differences between each of the four strains but nevertheless allowed
      differentiation of the lines deriving from the multiplication of one oocyst.
      Similar results were obtained with three methods of analysis: correspondence
      analysis, the hierarchical unweighted pair-group method with arithmetic averages
      (UP-GMA), and parsimony analysis. RAPD proved to be a useful technique for these
      intraspecific studies.

PMID- 7624293
TI  - Humoral immune responses to Theileria parva in cattle as measured by two
      dimensional western blotting.
AB  - Humoral immune responses to schizont antigens from six stocks of Theileria parva
      were compared by two-dimensional Western blotting using sera from cattle that had
      been infected with a T. parva stock or a clone. Isoelectric points of a
      polymorphic immunodominant molecule (PIM) of schizonts that induces strong
      antibody responses in cattle ranged from acidic to basic. Molecular masses (Mr)
      of the PIM of the respective T. parva stocks were as follows: T. parva Muguga, 86
      kDa; Mariakani, 83 kDa; Marikebuni, 83 kDa; Uganda, 83 kDa; T. parva Boleni, 83
      kDa; and T. parva 7014, 100 kDa. Among nine cattle infected with T. parva Muguga,
      four produced antibodies to a basic antigen having an Mr of 32 kDa. The PIM of T.
      parva Muguga, T. parva Boleni, and T. parva 7014 reacted strongly with serum
      obtained from an animal that had been infected with T. parva Muguga. Two
      dimensional Western blotting using antischizont monoclonal antibodies enabled us
      to differentiate between stocks of T. parva.

PMID- 7624294
TI  - Ultrastructure of spermiogenesis and spermatozoa of Neopolystoma spratti
      (Platyhelminthes, Monogenea, Polystomatidae).
AB  - Spermiogenesis in Neopolystoma spratti conforms to the basic pattern found in
      polyopisthocotylean monogeneans and in Trematoda Digenea and Trematoda
      Aspidogastrea. The zone of differentiation exhibits a complete ring of cortical
      microtubules, two initially free flagella with prominent striated rootlets and an
      intercentriolar body between them. Mitochondria and nucleus migrate into a median
      cytoplasmic process and flagella rotate and fuse with this process. Mitochondria
      fuse to form a single elongated mitochondrion and the nucleus moves to a distal
      location. Mature sperm have two incorporated axonemes for most of their length, a
      single elongate mitochondrion and a nucleus. Peripheral microtubules form an
      incomplete ring in the most proximal region and a complete ring in the adjacent
      region containing two axonemes and the mitochondrion. In the principal region
      (where the nucleus is present) they form an incomplete ring and are interpreted
      as originating from the dorsal and ventral faces of the median cytoplasmic
      process. Thus, although there are more microtubules in the principal region than
      at either end, the situation is essentially the same as that found in
      polyopisthocotylean monogeneans, digeneans and aspidogastreans, with no addition
      of extra lateral microtubules.

PMID- 7624295
TI  - A new blood fluke, Parasanguinicola vastispina gen. nov., sp. nov. (Trematoda:
      Sanguinicolidae), from sea bass Lates calcarifer (Centropomidae) cultured in
      Malaysia.
AB  - A new sanguinicolid blood fluke, Parasanguinicola vastispina, is described from
      sea bass Lates calcarifer cultured in Malaysia. It is distinguished by its
      massive armature and widely spaced genital pores, the female pore being pre
      ovarian. P. vastispina inhabits the branchial arteries, dorsal aorta, mesenteric
      venules and renal artery of its host. No pathological effect was observed in
      infected fish.

PMID- 7624297
TI  - Scanning electron microscopy of the human muscular sarcocyst.

PMID- 7624296
TI  - Continuous in vitro cultivation of erythrocytic stages of Babesia equi.
AB  - The protozoan parasite Babesia equi, a causative agent of equine piroplasmosis,
      was continuously cultivated in horse erythrocytes. The parasites were isolated
      from a carrier horse at a time when no parasite was detected in a thin blood
      smear. The culture medium consisted of modified medium 199 supplemented with 40%
      non-heat-inactivated horse serum in a humidified atmosphere containing 5% CO2, 2%
      O2, and 93% N2 at 37 degrees C. Parasites were detected after 2 days in culture.
      When the percentage of parasitized erythrocytes (PPE) reached 1%, the cultures
      were transferred into a humidified atmosphere of 5% CO2 in air. After 7 days the
      cultures were split at a ratio of 1:2, and after another 5 days they were split
      at a ratio of 1:4. From them on, cultures were split at a ratio of 1:4 routinely
      at 2-day intervals. The PPE ranged between 10% and 25%. Supplementation with
      hypoxanthine was essential for the initiation and propagation of cultures. In
      established cultures, hypoxanthine could be replaced by equimolar concentrations
      of adenosine or guanosine. Parasites from cultures could be cryopreserved and
      resuscitated. Cultures were maintained for more than 300 days.

PMID- 7624298
TI  - Pancreatic cancer symposium: epidemiology, etiology, pathogenesis, and therapy.

PMID- 7624299
TI  - "Human pancreas-specific protein" (procarboxypeptidase B): a valuable marker in
      pancreatitis?
AB  - Human pancreas-specific protein (PASP) has been characterized previously as a
      serum marker for pancreatitis. It was then identified as pancreatic
      procarboxypeptidase B (PCB). The aim of the present study was to verify the
      usefulness of PASP (PCB) as a serum marker in patients with acute (n = 20) and
      chronic (n = 12) pancreatitis and in those following endoscopic retrograde
      cholangiopancreaticography (ERCP) (n = 44). Serum PASP values were analyzed by
      radioimmunoassay, with a range of normal values between 15 and 111 ng/ml. Between
      April 1992 and September 1992, 20 subjects (19-86 years of age) with acute
      pancreatitis (alcoholic, 8; biliary, 8; other, 4) were studied. We found
      edematous pancreatitis in 17 cases and severe hemorrhagic pancreatitis in three
      cases. At admission, peak levels of PASP (average value, 1,976 +/- 329 ng/ml),
      pancreatic isoamylase (942 +/- 151 U/L) and lipase (2,946 +/- 534 U/L) were
      detected in 15 of 20, 16 of 20, and 12 of 20 cases, respectively. The etiology of
      the pancreatitis had no influence on the PASP values. Furthermore, 10 patients
      with alcoholic and two patients with nonalcoholic chronic pancreatitis (29-67
      years of age) were studied. The average peak level of PASP was 1,229 +/- 434
      ng/ml. In this group, PASP paralleled the time course of amylase and lipase.
      Maximal PASP, amylase, and lipase levels were found in 11 of 12, nine of 12, and
      five of 12 patients, respectively, on the day of admission. ERCP was performed in
      44 patients (36-87 years of age), demonstrating common bile duct stones in 16 and
      bile or pancreatic ductal tumors in 15 cases.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7624300
TI  - A multidimensional case-control study of dietary, alcohol, and tobacco habits in
      alcoholic men with chronic pancreatitis.
AB  - This study compared diet, type of alcoholism, and smoking in three groups of
      alcoholic men, with chronic pancreatitis (n = 56), with histological cirrhosis (n
      = 50), and without pancreatitis or cirrhosis (controls; n = 50) by a
      multidimensional analysis. Only patients in whom the first symptom of
      pancreatitis or cirrhosis was present for < 1 year before the interview were
      included. Patients with pancreatitis consumed more nonalcohol calories than
      cirrhotics (p < 0.05). The percentage of calories taken as proteins (p < 0.0003)
      and lipids (p < 0.0001) was higher and the percentage of calories taken as
      alcohol (p < 0.0003) was lower in patients with pancreatitis than in cirrhotics
      and control patients. There was no difference among the three groups for total
      calories/basal energy expenditure ratio, total nonalcohol calories/basal energy
      expenditure ratio, mineral and vitamin intake, or tobacco consumption. The
      duration of excessive alcohol consumption and the total alcohol consumption in
      patients with pancreatitis was similar to that of controls but lower than that of
      cirrhotics (p < 0.002 and p < 0.05, respectively). Three parameters were found to
      be independently different in the three groups by discriminant analysis:
      percentage of calories taken as lipids (p < 0.0001), duration of excessive
      alcohol consumption (p < 0.002), and percentage of calories taken as proteins (p
      < 0.08). These three parameters explained 24% of the variance. We conclude that
      the reasons alcoholic men develop chronic pancreatitis may be explained partly by
      dietary habits.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7624301
TI  - Carcinoma of the ampulla of Vater and mesenteric fibromatosis (desmoid tumor)
      associated with Gardner's syndrome: problems in management.
AB  - To date, 29 patients with Gardner's syndrome have been identified who developed
      carcinoma of the ampulla of Vater, and many others have been identified with
      mesenteric fibromatosis (desmoid tumor), but there have been only four cases of
      Gardner's syndrome with both ampullary carcinoma and mesenteric fibromatosis
      reported in the world literature. This article focuses on the complications and
      major problems in management resulting from the simultaneous occurrence of these
      two known features of Gardner's syndrome: carcinoma of the ampulla of Vater and
      fibromatosis (desmoid tumor) of the intestinal mesentery.

PMID- 7624302
TI  - Endoscopic ultrasonography in chronic pancreatitis: a comparative prospective
      study with conventional ultrasonography, computed tomography, and ERCP.
AB  - The usefulness and accuracy rate of endoscopic ultrasonography (EUS) in the
      diagnosis of chronic pancreatitis (CP) were prospectively evaluated in 81
      patients with suspected pancreatic disease. All underwent EUS, abdominal
      ultrasonography (AUS), and computed tomography (CT), and endoscopic retrograde
      cholangiopancreatography (ERCP) was performed in 55 of the cases. The diagnosis
      of CP was established in 44 patients (CP group) including 24 with a calcified
      form. No pancreatic disease was observed in 18 patients (control group), and 19
      patients had a pancreatic tumor. In the CP group AUS was less accurate than EUS
      in visualizing the pancreas, performances of CT scan being identical to EUS in
      this respect. A good correlation was observed between EUS and ERCP for
      visualization and measurement of the Wirsung duct. The most significant changes
      observed by EUS in the CP group were dilatation of the main pancreatic duct,
      heterogeneous echogenicity of the pancreatic parenchyma, and cysts < 20 mm in
      size even in noncalcified CP or with normal pancreatograms. Sensitivity of EUS
      for diagnosis of CP was 88% (AUS, 58%; ERCP, 74%; CT scan, 75%), the specificity
      being 100% for ERCP and EUS, 95% for CT scan, and 75% for AUS. The good
      performances of EUS allow early diagnosis of CP in symptomatic patients since
      heterogeneous echogenicity of the pancreatic parenchyma seems to be almost
      specifically associated with the disease.

PMID- 7624303
TI  - Radiolocalization of pancreatic carcinoma xenografts in nude mice with
      radiolabeled chimeric Fab fragments of anti-carcinoembryonic antigen monoclonal
      antibody A10.
AB  - Recombinant mouse-human chimeric Fab fragments of anti-carcinoembryonic antigen
      monoclonal antibody (MAb) A10 react with various GI carcinomas. We tested
      radiolocalization of pancreatic carcinoma xenografts in nude mice using
      radiolabeled chimeric A10 Fab fragments, comparing them with murine Fab fragments
      and parental MAb. For mice injected with chimeric A10 Fab fragments, we obtained
      significantly higher uptake in tumors than in normal tissues at 24 and 48 h after
      injection. In addition, tumor/normal tissues labeling ratios for chimeric A10 Fab
      fragment were significantly greater than those for murine MAb at 24 h
      postinfusion. However, no significant difference in biodistribution was observed
      between chimeric and murine Fab fragments. In autoradiography imaging studies, we
      obtained clearer tumor detection without visible uptake in normal organs for
      chimeric Fab fragments than for murine MAb. These results suggest that chimeric
      Fab fragments of A10 could be a potentially useful candidate for
      radioimmunodetection of pancreatic carcinomas.

PMID- 7624304
TI  - Biodistribution of murine and chimeric Fab fragments of the monoclonal antibody
      A7 in human pancreatic cancer.
AB  - Much recent research has focused on the use of monoclonal antibodies (MAbs) in
      the immunodetection of solid tumors. Fab fragments of MAbs are more suitable for
      immunoscintigraphy than intact MAbs. Recently, human-mouse chimeric antibodies
      have been developed in an effort to reduce human antimouse antibody (HAMA)
      production by murine MAbs in humans. In this study, 125I-labeled murine and
      chimeric Fab fragments of the MAb A7 were injected i.v. into nude mice bearing a
      human pancreatic cancer (HPC-YS) xenograft. The radioactivity in tumors and in
      normal tissues was subsequently measured. The tumor tissue/blood ratio (T/B) of
      125I-labeled murine and chimeric Fab fragments of MAb A7 increased with time in a
      similar manner and reached 9.68 +/- 2.54 and 10.49 +/- 1.50, respectively, 24 h
      after injection. Moreover, the T/Bs of 125I-labeled murine and chimeric Fab
      fragments of MAb A7 were greater than the T/B of intact MAb A7. When mice bearing
      tumors that did not react with MAb A7 were studied, 125I-labeled murine and
      chimeric Fab fragments did not localize specifically to the tumors. These results
      suggests that chimeric Fab fragments of MAb A7 are useful carriers of
      radionuclides for the immunodetection of human pancreatic cancer, with equivalent
      activity to murine Fab fragments and less theoretical potential to induce a HAMA
      response.

PMID- 7624305
TI  - The role of CCK and its analogues in the organogenesis of the fetal rat pancreas.
AB  - The gastrointestinal peptide cholecystokinin (CCK) has been shown to stimulate
      pancreatic growth in the adolescent and adult rat. However, little is known about
      the role of gastrointestinal hormones in the regulation of organ formation during
      fetal development. We therefore examined the effects of the CCK receptor
      antagonist devazepide (25 micrograms/h) and an antigastrin/CCK monoclonal
      immunoglobulin G on the maternal and fetal rat pancreas. These substances were
      infused subcutaneously with minipumps in female rats during the entire period of
      gestation. At the end of gestation, the rats were killed and the pancreata of the
      dams and their litter were examined for DNA and protein. In the dams, the
      receptor antagonist and the antibody against CCK/gastrin had no effect. In the
      newborns, the CCK receptor antagonist led to a significant reduction of the
      protein and DNA concentration [protein in controls, 105.0 +/- 3.75 micrograms/mg
      pancreatic tissue; in the antagonist group, 91.9 +/- 4.2 micrograms/mg pancreatic
      tissue (p < 0.05); DNA in controls, 1.28 +/- 0.19 micrograms/mg pancreatic
      tissue; in the antagonist group, 0.48 +/- 0.06 micrograms/mg pancreatic tissue (p
      < 0.05) (mean +/- SEM)]. Immune neutralization of CCK/gastrin in the maternal
      fetal circulation induced a reduction of the protein concentration in the fetal
      pancreas (85.3 +/- 3.06 micrograms/mg pancreatic tissue; p < 0.01) but had no
      effect on fetal pancreatic DNA. Additional experiments indicated effective
      concentrations of the CCK receptor antagonist in fetal pancreatic tissue and free
      binding sites of the circulating antibody. In conclusion, the study provides
      evidence that CCK and its analogues are involved in fetal pancreatic
      organogenesis.

PMID- 7624306
TI  - Insulin cells in rat whole-pancreas isografts display heterogeneous
      immunoreactivities and ultrastructure.
AB  - It has already been shown that insulin cells studied under experimental
      conditions exhibit differences in insulin immunoreactivity and insulin release.
      The aim of this study, therefore, was to investigate whether insulin cells
      themselves exhibit morphological abnormalities after transplantation. Insulin
      cells in rat pancreas isografts with preserved or suppressed exocrine secretion
      were studied immunocytochemically and ultrastructurally and compared with those
      of unoperated rats. In isografts with preserved exocrine secretion, cortical
      insulin cells connected to the exocrine parenchyma or to glucagon or somatostatin
      cells expressed mostly dense immunoreactivities for insulin and amylin. In
      addition, medullary insulin cells connected only to other insulin cells displayed
      faint immunoreactivities for both constituents as found in unoperated animals.
      After duct ligation, however, pancreatic ducts and elongated capillaries extended
      into the islets. Corresponding to the stages of islet fragmentation, the
      heterogeneity among insulin cells underwent changes and was finally abolished.
      Ultrastructurally, differences in the number of secretory granules paralleled the
      heterogeneity in insulin immunoreactivity. It is interesting to note that the
      heterogeneity among insulin cells is preserved after transplantation, indicating
      that this phenomenon might be of physiological relevance. The heterogeneity may
      implicate differences in insulin storage and release as found in insulin cells
      under normal conditions.

PMID- 7624307
TI  - Rapid local synchronization of action potentials: toward computation with coupled
      integrate-and-fire neurons.
AB  - The collective behavior of interconnected spiking nerve cells is investigated. It
      is shown that a variety of model systems exhibit the same short-time behavior and
      rapidly converge to (approximately) periodic firing patterns with locally
      synchronized action potentials. The dynamics of one model can be described by a
      downhill motion on an abstract energy landscape. Since an energy landscape makes
      it possible to understand and program computation done by an attractor network,
      the results will extend our understanding of collective computation from models
      based on a firing-rate description to biologically more realistic systems with
      integrate-and-fire neurons.

PMID- 7624308
TI  - Diffusion and formation of microtubule asters: physical processes versus
      biochemical regulation.
AB  - Microtubule asters forming the mitotic spindle are assembled around two
      centrosomes through the process of dynamic instability in which microtubules
      alternate between growing and shrinking states. By modifying the dynamics of this
      assembly process, cell cycle enzymes, such as cdc2 cyclin kinases, regulate
      length distributions in the asters. It is believed that the same enzymes control
      the number of assembled microtubules by changing the "nucleating activity" of the
      centrosomes. Here we show that assembly of microtubule asters may be strongly
      altered by effects connected with diffusion of tubulin monomers. Theoretical
      analysis of a simple model describing assembly of microtubule asters clearly
      shows the existence of a region surrounding the centrosome depleted in GTP
      tubulin. The number of assembled microtubules may in some cases be limited by
      this depletion effect rather than by the number of available nucleation sites on
      the centrosome.

PMID- 7624309
TI  - Genetic support for the out-of-Africa theory of human evolution.

PMID- 7624310
TI  - Genetic absolute dating based on microsatellites and the origin of modern humans.
AB  - We introduce a new genetic distance for microsatellite loci, incorporating
      features of the stepwise mutation model, and test its performance on
      microsatellite polymorphisms in humans, chimpanzees, and gorillas. We find that
      it performs well in determining the relations among the primates, but less well
      than other distance measures (not based on the stepwise mutation model) in
      determining the relations among closely related human populations. However, the
      deepest split in the human phylogeny seems to be accurately reconstructed by the
      new distance and separates African and non-African populations. The new distance
      is independent of population size and therefore allows direct estimation of
      divergence times if the mutation rate is known. Based on 30 microsatellite
      polymorphisms and a recently reported average mutation rate of 5.6 x 10(-4) at 15
      dinucleotide microsatellites, we estimate that the deepest split in the human
      phylogeny occurred about 156,000 years ago. Unlike most previous estimates, ours
      requires no external calibration of the rate of molecular evolution. We can use
      such calibrations, however, to test our estimate.

PMID- 7624311
TI  - Generation of a high-titer retroviral vector capable of expressing high levels of
      the human beta-globin gene.
AB  - Retrovirus-mediated gene transfer into hematopoietic cells may provide a means of
      treating both inherited and acquired diseases involving hematopoietic cells.
      Implementation of this approach for disorders resulting from mutations affecting
      the beta-globin gene (e.g., beta-thalassemia and sickle cell anemia), however,
      has been hampered by the inability to generate recombinant viruses able to
      efficiently and faithfully transmit the necessary sequences for appropriate gene
      expression. We have addressed this problem by carefully examining the
      interactions between retroviral and beta-globin gene sequences which affect
      vector transmission, stability, and expression. First, we examined the
      transmission properties of a large number of different recombinant proviral
      genomes which vary both in the precise nature of vector, beta-globin structural
      gene, and locus control region (LCR) core sequences incorporated and in the
      placement and orientation of those sequences. Through this analysis, we
      identified one specific vector, termed M beta 6L, which carries both the human
      beta-globin gene and core elements HS2, HS3, and HS4 from the LCR and faithfully
      transmits recombinant proviral sequences to cells with titers greater than 10(6)
      per ml. Populations of murine erythroleukemia (MEL) cells transduced by this
      virus expressed levels of human beta-globin transcript which, on a per gene copy
      basis, were 78% of the levels detected in an MEL-derived cell line, Hu11, which
      carries human chromosome 11, the site of the beta-globin locus. Analysis of
      individual transduced MEL cell clones, however, indicated that, while expression
      was detected in every clone tested (n = 17), the levels of human beta-globin
      treatment varied between 4% and 146% of the levels in Hu11. This clonal variation
      in expression levels suggests that small beta-globin LCR sequences may not
      provide for as strict chromosomal position-independent expression of beta-globin
      as previously suspected, at least in the context of retrovirus-mediated gene
      transfer.

PMID- 7624312
TI  - Effects of retroviral vector design on expression of human adenosine deaminase in
      murine bone marrow transplant recipients engrafted with genetically modified
      cells.
AB  - To determine which features of retroviral vector design most critically affect
      gene expression in hematopoietic cells in vivo, we have constructed a variety of
      different retroviral vectors which encode the same gene product, human adenosine
      deaminase (EC 3.5.4.4), and possess the same vector backbone yet differ
      specifically in transcriptional control sequences suggested by others to be
      important for gene expression in vivo. Murine bone marrow cells were transduced
      by each of the recombinant viruses and subsequently used to reconstitute the
      hematopoietic system of lethally irradiated recipients. Five to seven months
      after transplantation, analysis of the peripheral blood of animals transplanted
      with cells transduced by vectors which employ viral long terminal repeats (LTRs)
      for gene expression indicated that in 83% (77/93) of these animals, the level of
      human enzyme was equal to or greater than the level of endogenous murine enzyme.
      Even in bone marrow transplant recipients reconstituted for over 1 year,
      significant levels of gene expression were observed for each of the vectors in
      their bone marrow, spleen, macrophages, and B and T lymphocytes. However,
      derivatives of the parental MFG-ADA vector which possess either a single base
      mutation (termed B2 mutation) or myeloproliferative sarcoma virus LTRs rather
      than the Moloney murine leukemia virus LTRs led to significantly improved gene
      expression in all lineages. These studies indicate that retroviral vectors which
      employ viral LTRs for the expression of inserted sequences make it possible to
      obtain high levels of a desired gene product in most hematopoietic cell lineages
      for close to the lifetime of bone marrow transplant recipients.

PMID- 7624313
TI  - Inhibitors of human heart chymase based on a peptide library.
AB  - We have synthesized two sets of noncleavable peptide-inhibitor libraries to map
      the S and S' subsites of human heart chymase. Human heart chymase is a
      chymotrypsin-like enzyme that converts angiotensin I to angiotensin II. The first
      library consists of peptides with 3-fluorobenzylpyruvamides in the P1 position.
      (Amino acid residues of substrates numbered P1, P2, etc., are toward the N
      terminal direction, and P'1, P'2, etc., are toward the C-terminal direction from
      the scissile bond.) The P'1 and P'2 positions were varied to contain each one of
      the 20 naturally occurring amino acids and P'3 was kept constant as an arginine.
      The second library consists of peptides with phenylalanine keto-amides at P1,
      glycine in P'1, and benzyloxycarbonyl (Z)-isoleucine in P4. The P2 and P3
      positions were varied to contain each of the naturally occurring amino acids,
      except for cysteine and methionine. The peptides of both libraries are attached
      to a solid support (pins). The peptides are evaluated by immersing the pins in a
      solution of the target enzyme and evaluating the amount of enzyme absorbed. The
      pins with the best inhibitors will absorb most enzyme. The libraries select the
      best and worst inhibitors within each group of peptides and provide an
      approximate ranking of the remaining peptides according to Ki. Through this
      library, we determined that Z-Ile-Glu-Pro-Phe-CO2Me and (F)-Phe-CO-Glu-Asp-ArgOMe
      should be the best inhibitors of chymase in this collection of peptide
      inhibitors. We synthesized the peptides and found Ki values were 1 nM and 1
      microM, respectively. The corresponding Ki values for chymotrypsin were 10 nM and
      100 microM. The use of libraries of inhibitors has advantages over the classical
      method of synthesis of potential inhibitors in solution: the libraries are
      reusable, the same libraries can be used with a variety of different serine
      proteases, and the method allows the screening of hundreds of compounds in short
      periods of time.

PMID- 7624314
TI  - An oleate 12-hydroxylase from Ricinus communis L. is a fatty acyl desaturase
      homolog.
AB  - Recent spectroscopic evidence implicating a binuclear iron site at the reaction
      center of fatty acyl desaturases suggested to us that certain fatty acyl
      hydroxylases may share significant amino acid sequence similarity with
      desaturases. To test this theory, we prepared a cDNA library from developing
      endosperm of the castor-oil plant (Ricinus communis L.) and obtained partial
      nucleotide sequences for 468 anonymous clones that were not expressed at high
      levels in leaves, a tissue deficient in 12-hydroxyoleic acid. This resulted in
      the identification of several cDNA clones encoding a polypeptide of 387 amino
      acids with a predicted molecular weight of 44,407 and with approximately 67%
      sequence homology to microsomal oleate desaturase from Arabidopsis. Expression of
      a full-length clone under control of the cauliflower mosaic virus 35S promoter in
      transgenic tobacco resulted in the accumulation of low levels of 12-hydroxyoleic
      acid in seeds, indicating that the clone encodes the castor oleate hydroxylase.
      These results suggest that fatty acyl desaturases and hydroxylases share similar
      reaction mechanisms and provide an example of enzyme evolution.

PMID- 7624315
TI  - Sex proportions of Haemoproteus blood parasites and local mate competition.
AB  - Recent genetic evidence suggests that parasitic protozoa often reproduce by
      "selfing," defined as sexual stages from a single, clonal lineage fertilizing
      each other. Selfing favors production of an excess of female over male progeny.
      We tested whether the proportion of male gametocytes of blood parasites of the
      genus Haemoproteus was affected by variables that could influence the probability
      of selfing. Proportions of male Haemoproteus gametocytes from 11 passerine host
      populations were not affected by the age of the parasites' avian hosts, date in
      season, sex of host, intensity of host's infection, or prevalence of parasites
      within host populations.

PMID- 7624316
TI  - Cloning and expression of two brain-specific inwardly rectifying potassium
      channels.
AB  - We have cloned two inwardly rectifying K+ channels that occur selectively in
      neurons in the brain and are designated BIRK (brain inwardly rectifying K+)
      channels. BIRK1 mRNA is extremely abundant and is enriched in specific brainstem
      nuclei, BIRK1 displays a consensus phosphate-binding loop, and expression in
      Xenopus oocytes has shown that its conductance is inhibited by ATP and adenosine
      5'-[gamma-thio]triphosphate. BIRK2 is far less abundant and is selectively
      localized in telencephalic neurons. BIRK2 has a consensus sequence for cAMP
      dependent phosphorylation.

PMID- 7624317
TI  - Competence for collagenase gene expression by tissue fibroblasts requires
      activation of an interleukin 1 alpha autocrine loop.
AB  - The enzyme collagenase (EC 3.4.24.7), a key mediator in biological remodeling,
      can be induced in early-passage fibroblasts by a wide variety of agents and
      conditions. In contrast, at least some primary tissue fibroblasts are incompetent
      to synthesize collagenase in response to many of these stimulators. In this
      study, we investigate mechanisms controlling response to two of the conditions in
      question: (i) trypsin or cytochalasin B, which disrupt actin stress fibers, or
      (ii) phorbol 12-myristate 13-acetate (PMA), which activates growth factor
      signaling pathways. We demonstrate that collagenase expression stimulated by
      trypsin or cytochalasin B is regulated entirely through an autocrine cytokine,
      interleukin 1 alpha (IL-1 alpha). The IL-1 alpha intermediate also constitutes
      the major mechanism by which PMA stimulates collagenase expression, although a
      second signaling pathway(s) contributes to a minor extent. Elevation of the IL-1
      alpha level in response to stimulators is found to be sustained by means of an
      autocrine feedback loop in early-passage fibroblast cultures. In contrast,
      fibroblasts freshly isolated from the tissue are incompetent to activate and
      sustain the IL-1 alpha feedback loop, even though they synthesize collagenase in
      response to exogenous IL-1. We conclude that this is the reason why tissue
      fibroblasts are limited, in comparison with subcultured fibroblasts, in their
      capacity to synthesize collagenase. Activation of the IL-1 alpha feedback loop,
      therefore, seems likely to be an important mechanism by which resident tissue
      cells adopt the remodeling phenotype.

PMID- 7624318
TI  - Stringent chemical and thermal regulation of recombinant gene expression by
      vaccinia virus vectors in mammalian cells.
AB  - We developed a stringently regulated expression system for mammalian cells that
      uses (i) the RNA polymerase, phi 10 promoter, and T phi transcriptional
      terminator of bacteriophage T7; (ii) the lac repressor, lac operator, rho
      independent transcriptional terminators and the gpt gene of Escherichia coli;
      (iii) the RNA translational enhancer of encephalomyocarditis virus; and (iv) the
      genetic background of vaccinia virus. In cells infected with the recombinant
      vaccinia virus, reporter beta-galactosidase synthesis was not detected in the
      absence of inducer. An induction of at least 10,000- to 20,000-fold occurred upon
      addition of isopropyl beta-D-thiogalactopyranoside or by temperature elevation
      from 30 to 37 degrees C using a temperature-sensitive lac repressor. Regulated
      synthesis of the secreted and highly glycosylated human immunodeficiency virus 1
      envelope protein gp120 was also demonstrated. Yields of both proteins were
      approximately 2 mg per 10(8) cells in 24 hr. Plasmid transfer vectors for cloning
      and expression of complete or incomplete open reading frames in recombinant
      vaccinia viruses are described.

PMID- 7624319
TI  - Extrapituitary expression of the rat V1b vasopressin receptor gene.
AB  - [Arg8]vasopressin (AVP) stimulates adrenocorticotropic hormone release from the
      anterior pituitary by acting on the V1b AVP receptor. This receptor can be
      distinguished from the vascular/hepatic V1a and renal V2 AVP receptors by its
      differential binding affinities for structural analogous of AVP. Recent studies
      have shown that the cloned V1a and V2 receptors are structurally related. We have
      isolated a clone encoding the V1b receptor from a rat pituitary cDNA library
      using polymerase chain reaction (PCR)-based methodology. The rat V1b receptor is
      a protein of 421 amino acids that has 37-50% identity with the V1a and V2
      receptors. Homology is particularly high in the seven putative membrane-spanning
      domains of these guanine nucleotide-binding protein-coupled receptors. Expression
      of the recombinant receptor in mammalian cells shows the same binding specificity
      for AVP agonists and antagonists as the rat pituitary V1b receptor. AVP
      stimulated phosphotidylinositol hydrolysis and intracellular Ca2+ mobilization in
      Chinese hamster ovary or COS-7 cells expressing the cloned receptor suggest
      second messenger signaling through phospholipase C. RNA blot analysis, reverse
      transcription PCR, and in situ hybridization studies reveal that V1b receptor
      mRNA is expressed in the majority of pituitary corticotropes as well as in
      multiple brain regions and a number of peripheral tissues, including kidney,
      thymus, heart, lung, spleen, uterus, and breast. Thus, the V1b receptor must
      mediate some of the diverse biological effects of AVP in the pituitary as well as
      other organs.

PMID- 7624320
TI  - Thrombospondin 1 expression in transformed endothelial cells restores a normal
      phenotype and suppresses their tumorigenesis.
AB  - Murine endothelial cells are readily transformed in a single step by the
      polyomavirus oncogene encoding middle-sized tumor antigen. These cells (bEND.3)
      form tumors (hemangiomas) in mice which are lethal in newborn animals. The bEND.3
      cells rapidly proliferate in culture and express little or no thrombospondin 1
      (TS1). To determine the role of TS1 in regulation of endothelial cell phenotype,
      we stably transfected bEND.3 cells with a human TS1 expression vector. The cells
      expressing human TS1 were readily identified by their altered morphology and
      exhibited a slower growth rate and lower saturation density than the parental
      bEND.3 cells. The TS1-expressing cells also formed aligned cords of cells instead
      of clumps or cysts in Matrigel. Moreover, while the bEND.3 cells formed large
      tumors in nude mice within 48 hr, the TS1-expressing cells failed to form tumors
      even after 1 month. The TS1-transfected cells expressed transforming growth
      factor beta mRNA and bioactivity at levels similar to those of the parental or
      vector-transfected bEND.3 cells, indicating that the effects of TS1 expression
      are not due to the activation of transforming growth factor beta by TS1. TS1
      expression resulted in a > 100-fold decrease in net fibrinolytic (urokinase-type
      plasminogen activator, uPA) activity due to more plasminogen-activator inhibitor
      1 and less uPA secretion. TS1 thus appears to be an important regulator of
      endothelial cell phenotype required for maintaining the quiescent, differentiated
      state.

PMID- 7624321
TI  - Considerations on the folding topology and evolutionary origin of cadherin
      domains.
AB  - Cell-cell adhesion in zonula adherens and desmosomal junctions is mediated by
      cadherins, and recent crystal structures of the first domain from murine N
      cadherin provide a plausible molecular basis for this adhesive action. A
      structure-based sequence analysis of this adhesive domain indicates that its fold
      is common to all extracellular cadherin domains. The cadherin folding topology is
      also shown to be similar to immunoglobulin-like domains and to other Greek-key
      beta-sandwich structures, as diverse as domains from plant cytochromes, bacterial
      cellulases, and eukaryotic transcription factors. Sequence similarities between
      cadherins and these other molecules are very low, however, and intron patterns
      are also different. On balance, independent origins for a favorable folding
      topology seem more likely than evolutionary divergence from an ancestor common to
      cadherins and immunoglobulins.

PMID- 7624322
TI  - Transfection of the human heme oxygenase gene into rabbit coronary microvessel
      endothelial cells: protective effect against heme and hemoglobin toxicity.
AB  - Heme oxygenase (HO) is a stress protein and has been suggested to participate in
      defense mechanisms against agents that may induce oxidative injury such as
      metals, endotoxin, heme/hemoglobin, and various cytokines. Overexpression of HO
      in cells might therefore protect against oxidative stress produced by certain of
      these agents, specifically heme and hemoglobin, by catalyzing their degradation
      to bilirubin, which itself has antioxidant properties. We report here the
      successful in vitro transfection of rabbit coronary microvessel endothelial cells
      with a functioning gene encoding the human HO enzyme. A plasmid containing the
      cytomegalovirus promoter and the human HO cDNA complexed to cationic liposomes
      (Lipofectin) was used to transfect rabbit endothelial cells. Cells transfected
      with human HO exhibited an approximately 3.0-fold increase in enzyme activity and
      expressed a severalfold induction of human HO mRNA as compared with endogenous
      rabbit HO mRNA. Transfected and nontransfected cells expressed factor VIII
      antigen and exhibited similar acetylated low-density lipoprotein uptake (two
      important features that characterize endothelial cells) with > 85% of cells
      staining positive for each marker. Moreover, cells transfected with the human HO
      gene acquired substantial resistance to toxicity produced by exposure to
      recombinant hemoglobin and heme as compared with nontransfected cells. The
      protective effect of HO overexpression against heme/hemoglobin toxicity in
      endothelial cells shown in these studies provides direct evidence that the
      inductive response of human HO to such injurious stimuli represents an important
      tissue adaptive mechanism for moderating the severity of cell damage produced by
      these blood components.

PMID- 7624323
TI  - Transition metal ion activation of DNA binding by the diphtheria tox repressor
      requires the formation of stable homodimers.
AB  - The diphtheria tox repressor (DtxR) is a transition metal ion-dependent
      regulatory element that controls the expression of diphtheria toxin and several
      genes involved in the synthesis of siderophores in Corynebacterium diphtheriae.
      In the presence of transition metal ions apo-DtxR becomes activated and
      specifically binds to its target DNA sequences. We demonstrate by glutaraldehyde
      cross-linking that monomeric apo-DtxR is in weak equilibrium with a dimeric form
      and that upon addition of activating metal ions to the reaction mixture a dimeric
      complex is stabilized. Addition of the DNA-binding-defective mutant apo
      DtxR(delta 1-47) to apo-DtxR in the absence of transition metal ions inhibits
      conversion of the apo-repressor to its activated DNA-binding form. We also show
      that the binding of Ni2+ to both apo-DtxR and apo-DtxR(delta 1-47) is cooperative
      and that upon ion binding there is a conformational change in the environment of
      the indole ring moiety of Trp-104. For the wild-type repressor the consequences
      of this conformational change include a shift in equilibrium toward dimer
      formation and activation of target DNA binding by the repressor. We conclude that
      the formation of DtxR homodimers is mediated through a protein-protein
      interaction domain that is also activated on metal ion binding.

PMID- 7624324
TI  - MEKK1 phosphorylates MEK1 and MEK2 but does not cause activation of mitogen
      activated protein kinase.
AB  - A constitutively active fragment of rat MEK kinase 1 (MEKK1) consisting of only
      its catalytic domain (MEKK-C) expressed in bacteria quantitatively activates
      recombinant mitogen-activated protein (MAP) kinase/extracellular signal-regulated
      protein kinase (ERK) kinases 1 and 2 (MEK1 and MEK2) in vitro. Activation of MEK1
      by MEKK-C is accompanied by phosphorylation of S218 and S222, which are also
      phosphorylated by the protein kinases c-Mos and Raf-1. MEKK1 has been implicated
      in regulation of a parallel but distinct cascade that leads to phosphorylation of
      N-terminal sites on c-Jun; thus, its role in the MAP kinase pathway has been
      questioned. However, in addition to its capacity to phosphorylate MEK1 in vitro,
      MEKK-C interacts with MEK1 in the two-hybrid system, and expression of mouse
      MEKK1 or MEKK-C in mammalian cells causes constitutive activation of both MEK1
      and MEK2. Neither cotransfected nor endogenous ERK2 is highly activated by MEKK1
      compared to its stimulation by epidermal growth factor in spite of significant
      activation of endogenous MEK. Thus, other as yet undefined mechanisms may be
      involved in determining information flow through the MAP kinase and related
      pathways.

PMID- 7624325
TI  - Documentation of reticulate evolution in peonies (Paeonia) using internal
      transcribed spacer sequences of nuclear ribosomal DNA: implications for
      biogeography and concerted evolution.
AB  - The internal transcribed spacers (ITS) of nuclear ribosomal DNA of 33 species of
      genus Paeonia (Paeoniaceae) were sequenced. In section Paeonia, different
      patterns of nucleotide additivity were detected in 14 diploid and tetraploid
      species at sites that are variable in the other 12 species of the section,
      suggesting that reticulate evolution has occurred. Phylogenetic relationships of
      species that do not show additivity, and thus ostensibly were not derived through
      hybridization, were reconstructed by parsimony analysis. The taxa presumably
      derived through reticulate evolution were then added to the phylogenetic tree
      according to additivity from putative parents. The study provides an example of
      successfully using ITS sequences to reconstruct reticulate evolution in plants
      and further demonstrates that the sequence data could be highly informative and
      accurate for detecting hybridization. Maintenance of parental sequences in the
      species of hybrid origin is likely due to slowing of concerted evolution caused
      by the long generation time of peonies. The partial and uneven homogenization of
      parental sequences displayed in nine species of putative hybrid origin may have
      resulted from gradients of gene conversion. The documented hybridizations may
      have occurred since the Pleistocene glaciations. The species of hybrid origin and
      their putative parents are now distantly allopatric. Reconstruction of reticulate
      evolution with sequence data, therefore, provides gene records for distributional
      histories of some of the parental species.

PMID- 7624326
TI  - Reproduction and sera embryotoxicity after immunization of monkeys with the
      laminin peptides YIGSR, RGD, and IKVAV.
AB  - Monkeys with excellent reproductive histories were immunized with the laminin
      peptides YIGSR, RGD, IKVAV, and YD, a control sequence with no known biological
      function. Sera from the YIGSR-immunized monkey became toxic, causing neural tube
      defects in whole rat embryo cultures, and this monkey experienced fetal loss
      after immunization. Sera from the RGD-immunized monkey also became embryotoxic in
      culture after immunization, but this monkey appeared to become infertile as she
      failed to initiate a pregnancy for at least 2 years after immunization. In
      contrast, embryos cultured on sera from the IKVAV- or YD-immunized monkeys were
      predominantly normal and both monkeys completed successful pregnancies. Antibody
      levels to the respective peptides or to laminin were not predictive of
      embryotoxicity, but antibody binding to homogenized yolk sacs as well as to yolk
      sacs of cultured embryos was associated with sera embryotoxicity and reproductive
      outcomes in vivo. These observations suggested that the laminin sequences YIGSR
      and RGD may play a role in immune-mediated reproductive failure by reacting
      directly with embryonic tissue and could provide a basis for identifying
      individuals at risk for both spontaneous abortion and infertility.

PMID- 7624327
TI  - A defective signal peptide in the maize high-lysine mutant floury 2.
AB  - The maize floury 2 (fl2) mutation enhances the lysine content of the grain, but
      the soft texture of the endosperm makes it unsuitable for commercial production.
      The mutant phenotype is linked with the appearance of a 24-kDa alpha-zein protein
      and increased synthesis of binding protein, both of which are associated with
      irregularly shaped protein bodies. We have cloned the gene encoding the 24-kDa
      protein and show that it is expressed as a 22-kDa alpha-zein with an uncleaved
      signal peptide. Comparison of the deduced N-terminal amino acid sequence of the
      24-kDa alpha-zein protein with other alpha-zeins revealed an alanine to valine
      substitution at the C-terminal position of the signal peptide, a histidine
      insertion within the seventh alpha-helical repeat, and an alanine to threonine
      substitution with the same alpha-helical repeat of the protein. Structural
      defects associated with this alpha-zein explain many of the phenotypic effects of
      the fl2 mutation.

PMID- 7624329
TI  - Augmented DNA-binding activity of p53 protein encoded by a carboxyl-terminal
      alternatively spliced mRNA is blocked by p53 protein encoded by the regularly
      spliced form.
AB  - DNA-binding activity of the wild-type p53 is central to its function in vivo.
      However, recombinant or in vitro translated wild-type p53 proteins, unless
      modified, are poor DNA binders. The fact that the in vitro produced protein gains
      DNA-binding activity upon modification at the C terminus raises the possibility
      that similar mechanisms may exist in the cell. Data presented here show that a C
      terminal alternatively spliced wild-type p53 (ASp53) mRNA expressed by bacteria
      or transcribed in vitro codes for a p53 protein that efficiently binds DNA. Our
      results support the conclusion that the augmented DNA binding activity of an
      ASp53 protein is probably due to attenuation of the negative effect residing at
      the C terminus of the wild-type p53 protein encoded by the regularly spliced mRNA
      (RSp53) rather than acquisition of additional functionality by the alternatively
      spliced C' terminus. In addition, we found that ASp53 forms a complex with the
      non-DNA-binding RSp53, which in turn blocks the DNA-binding activity of ASp53.
      Interaction between these two wild-type p53 proteins may underline a mechanism
      that controls the activity of the wild-type p53 protein in the cell.

PMID- 7624328
TI  - Rescue of defective mitogenic signaling by D-type cyclins.
AB  - Three gene products, including Myc and the D- and E-type G1 cyclins, are rate
      limiting for G1 progression in mammalian fibroblasts. Quiescent mouse NIH 3T3
      fibroblasts engineered to express a mutant colony-stimulating factor (CSF-1)
      receptor (CSF-1R 809F) fail to synthesize c-myc and cyclin D1 mRNAs upon CSF-1
      stimulation and remain arrested in early G1 phase. Ectopic expression of c-myc or
      either of three D-type cyclin genes, but not cyclin E, resensitized these cells
      to the mitogenic effects of CSF-1, enabling them to proliferate continuously in
      liquid culture and to form colonies in agar in response to the growth factor.
      Rescue by cyclin D1 was enhanced by c-myc but not by cyclin E and was reversed by
      infecting cyclin D1-reconstituted cells with a retroviral vector encoding
      catalytically inactive cyclin-dependent kinase 4. Induction of cyclin D1 mRNA by
      CSF-1 was restored in cells forced to express c-myc, and vice versa, suggesting
      that expression of the two genes is interdependent. Cells reconstituted with c
      myc were prevented from entering S phase when microinjected with a monoclonal
      antibody to cyclin D1, and conversely, those rescued by cyclin D1 were inhibited
      from forming CSF-1-dependent colonies when challenged with a dominant-negative c
      myc mutant. Cyclin D mutants defective in binding to the retinoblastoma protein
      were impaired in rescuing mitogenic signaling. Therefore, Myc and D-type cyclins
      collaborate during the mitogenic response to CSF-1, whereas cyclin E functions in
      a separate pathway.

PMID- 7624330
TI  - Interleukin 12 suppresses autoantibody production by reversing helper T-cell
      phenotype in hepatitis B e antigen transgenic mice.
AB  - Helper T (Th) cells are classified as Th1 or Th2 cells by virtue of cytokine
      secretion and function as mediators of cellular or humoral immunity,
      respectively. Cytokines also regulate the differentiation of Th cells. For
      example, interleukin (IL)-12 promotes Th1 and suppresses Th2 cell development,
      suggesting that IL-12 may be useful therapeutically in Th2-mediated autoimmune
      and allergic disorders. Therefore, the effect of systemic IL-12 treatment on in
      vivo autoantibody synthesis in hepatitis B e antigen (HBeAg)-expressing
      transgenic mice, which is dependent on self-reactive Th2 cells, was examined. Low
      dose IL-12 significantly inhibited autoantibody production by shifting the Th2
      mediated response toward Th1 predominance. Additionally, previous studies suggest
      that a predominance of HBeAg-specific Th2-type cells may contribute to chronicity
      in hepatitis B virus infection. Therefore, IL-12 may also prove beneficial in
      modulating the HBeAg-specific Th response to favor viral clearance in chronic
      hepatitis B virus infection.

PMID- 7624331
TI  - Limbic epilepsy in transgenic mice carrying a Ca2+/calmodulin-dependent kinase II
      alpha-subunit mutation.
AB  - Multifunctional Ca2+/calmodulin-dependent protein kinase II (CaMK) phosphorylates
      proteins pivotally involved in diverse neuronal processes and thereby coordinates
      cellular responses to external stimuli that regulate intracellular Ca2+ [Hanson,
      P. I. & Schulman, H. (1992) Annu. Rev. Biochem. 61, 559-664]. Despite extensive
      study, the impact of this enzyme on control of the excitability of neuron
      populations in the mammalian nervous system in situ is unknown. To address this
      question, we studied transgenic mice carrying a null mutation (-/-) for the alpha
      subunit of CaMK. In contrast to wild-type littermates, null mutants exhibit
      profound hyperexcitability, evident in epileptic seizures involving limbic
      structures including the hippocampus. No evidence of increased excitability was
      detected in mice carrying null mutations of the gamma isoform of protein kinase
      C, underscoring the specificity of the effect of CaMK. CaMK plays a powerful and
      previously underappreciated role in control of neuronal excitability in the
      mammalian nervous system. These insights have important implications for analyses
      of mechanisms of epilepsy and, perhaps, learning and memory.

PMID- 7624332
TI  - On the existence and implications of an inverse folding code in proteins.
AB  - The existence of a code relating the set of possible sequences at a given
      position in a protein backbone to the local structure at that location is
      investigated. It is shown that only 73% of 4-C alpha structure fragments in a
      sample of 114 protein structures exhibit a preference for a particular set of
      sequences. The remaining structures can accommodate essentially any sequence. The
      structures that encode specific sequence distributions include the classical
      "secondary" structures, with the notable exception of planar (beta) bends. It is
      suggested that this has implications as to the mechanism of folding in proteins
      with extensive sheet/barrel structure. The possible role of structures that do
      not encode specific sequences as mutation hot spots is noted.

PMID- 7624333
TI  - Multiple origins of the yucca-yucca moth association.
AB  - The association of species of yucca and their pollinating moths is considered one
      of the two classic cases of obligate mutualism between floral hosts and their
      pollinators. The system involves the active collection of pollen by females of
      two prodoxid moth genera and the subsequent purposeful placement of the pollen on
      conspecific stigmas of species of Yucca. Yuccas essentially depend on the moths
      for pollination and the moths require Yucca ovaries for oviposition. Because of
      the specificity involved, it has been assumed that the association arose once,
      although it has been suggested that within the prodoxid moths as a whole,
      pollinators have arisen from seed predators more than once. We show, by using
      phylogenies generated from three molecular data sets, that the supposed
      restriction of the yucca moths and their allies to the Agavaceae is an artifact
      caused by an incorrect circumscription of this family. In addition we provide
      evidence that Yucca is not monophyletic, leading to the conclusion that the
      modern Yucca-yucca moth relationship developed independently more than once by
      colonization of a new host.

PMID- 7624334
TI  - Mucosal and systemic immune responses to a recombinant protein expressed on the
      surface of the oral commensal bacterium Streptococcus gordonii after oral
      colonization.
AB  - To circumvent the need to engineer pathogenic microorganisms as live vaccine
      delivery vehicles, a system was developed which allowed for the stable expression
      of a wide range of protein antigens on the surface of Gram-positive commensal
      bacteria. The human oral commensal Streptococcus gordonii was engineered to
      surface express a 204-amino acid allergen from hornet venom (Ag5.2) as a fusion
      with the anchor region of the M6 protein of Streptococcus pyogenes. The
      immunogenicity of the M6-Ag5.2 fusion protein was assessed in mice inoculated
      orally and intranasally with a single dose of recombinant bacteria, resulting in
      the colonization of the oral/pharyngeal mucosa for 10-11 weeks. A significant
      increase of Ag5.2-specific IgA with relation to the total IgA was detected in
      saliva and lung lavages when compared with mice colonized with wild-type S.
      gordonii. A systemic IgG response to Ag5.2 was also induced after oral
      colonization. Thus, recombinant Gram-positive commensal bacteria may be a safe
      and effective way of inducing a local and systemic immune response.

PMID- 7624335
TI  - Identification of NAB1, a repressor of NGFI-A- and Krox20-mediated transcription.
AB  - NGFI-A (also called Egr1, Zif268, or Krox24) and the closely related proteins
      Krox20, NGFI-C, and Egr3 are zinc-finger transcription factors encoded by
      immediate-early genes which are induced by a wide variety of extracellular
      stimuli. NGFI-A has been implicated in cell proliferation, macrophage
      differentiation, synaptic activation, and long-term potentiation, whereas Krox20
      is critical for proper hindbrain segmentation and peripheral nerve myelination.
      In previous work, a structure/function analysis of NGFI-A revealed a 34-aa
      inhibitory domain that was hypothesized to be the target of a cellular factor
      that represses NGFI-A transcriptional activity. Using the yeast two-hybrid
      system, we have isolated a cDNA clone which encodes a protein that interacts with
      this inhibitory domain and inhibits the ability of NGFI-A to activate
      transcription. This NGFI-A-binding protein, NAB1, is a 570-aa nuclear protein
      that bears no obvious sequence homology to known proteins. NAB1 also represses
      Krox20 activity, but it does not influence Egr3 or NGFI-G, thus providing a
      mechanism for the differential regulation of this family of immediate-early
      transcription factors.

PMID- 7624336
TI  - Submillisecond folding of monomeric lambda repressor.
AB  - The folding kinetics of a truncated form of the N-terminal domain of phage lambda
      repressor [lambda 6-85] has been investigated by using the technique of dynamic
      NMR. lambda 6-85 has been shown previously to fold in a purely two-state fashion.
      This allows the determination of folding and unfolding rates from simulation of
      the exchange-broadened aromatic resonances of Tyr-22. The folding kinetics were
      determined over a range of 1.35 to 3.14 M urea. The urea dependence of both
      folding and unfolding rate constants is exponential, suggesting that the rate
      determining step is invariant at the urea concentrations studied. The folding and
      unfolding rates extrapolated to 0 M urea at 37 degrees C are 3600 +/- 400 s-1 and
      27 +/- 6 s-1, respectively. The observed lambda 6-85 folding rate constant
      exceeds that of other fast-folding globular proteins by a factor of 14-54. The
      urea dependence of the folding and unfolding rate constants suggests that the
      transition state of the rate-determining step is considerably more exposed to
      solvent than previously studied protein-folding transition states. The surprising
      rapidity of lambda 6-85 folding and unfolding may be the consequence of its all
      helical secondary structure. These kinetic results clearly demonstrate that all
      of the fundamental events of protein folding can occur on the submillisecond time
      scale.

PMID- 7624337
TI  - Trapping of branched DNA in microfabricated structures.
AB  - We have observed electrostatic trapping of tribranched DNA molecules undergoing
      electrophoresis in a microfabricated pseudo-two-dimensional array of posts.
      Trapping occurs in a unique transport regimen in which the electrophoretic
      mobility is extremely sensitive to polymer topology. The arrest of branched
      polymers is explained by considering their center-of-mass motion; in certain
      conformations, owing to the constraints imposed by the obstacles a molecule
      cannot advance without the center of mass first moving a short distance
      backwards. The depth of the resulting local potential well can be much greater
      than the thermal energy so that escape of an immobilized molecule can be
      extremely slow. We summarize the expected behavior of the mobility as a function
      of field strength and topology and point out that the microfabricated arrays are
      highly suitable for detecting an extremely small number of branched molecules in
      a very large population of linear molecules.

PMID- 7624339
TI  - The kinetics of quantal transmitter release from retinal amacrine cells.
AB  - Exocytosis of transmitter at most synapses is a very fast process triggered by
      the entry of Ca2+ during an action potential. A reasonable expectation is that
      the fast step of exocytosis is followed by slow steps readying another vesicle
      for exocytosis but the identity and kinetics of these steps are presently
      unclear. By voltage clamping both pre- and postsynaptic neurons in an isolated
      pair of retinal amacrine cells, we have measured evoked synaptic currents and
      responses to single vesicles of transmitter (minis). From these currents, we have
      computed the rate of exocytosis during a sustained presynaptic depolarization. We
      show here that for these cells, release is consistent with a scheme of "fire and
      reload." Large Ca2+ influx causes the rapid release of a small number of
      vesicles, typically approximately 10 per presynaptic neuron, likely corresponding
      to those vesicles already docked. After this spike of exocytosis whose peak is
      150 quanta per release site per s, continued Ca2+ influx sustains release at only
      22 quanta per release site per s, probably rate-limited by the docking of fresh
      vesicles.

PMID- 7624338
TI  - A mitochondrial DNA clone is associated with increased risk for Alzheimer
      disease.
AB  - Severe mitochondrial genetic mutations lead to early degeneration of specific
      human tissues; milder mitochondrial mutations may cause degeneration at a later
      point in life. A mutation at position 4336 was reported to occur at increased
      frequency in individuals with Alzheimer disease (AD) and Parkinson disease
      [Shoffner, J. M., Brown, M. D., Torroni, A., Lott, M. T., Cabell, M. F., Mirra,
      S. S., Beal, M. F., Yang, C.-C., Gearing, M., Salvo, R., Watts, R. L., Juncos, J.
      L., Hansen, L. A., Crain, B. J., Fayad, M., Reckord, C. L. & Wallace, D. C.
      (1993) Genomics 17, 171-184]. We have investigated the notion that this mutation
      leads to excess risk of AD by using a case-control study design of 72 AD
      autopsies and 296 race- and age-matched controls. The 4336G mutation occurred at
      higher frequency in AD autopsies than age-matched controls, a statistically
      significant difference. Evolutionary analysis of mtDNAs bearing the 4336G
      mutation indicated they were more closely related to each other than to other
      mtDNAs, consistent with the model of a single origin for this mutation. The tight
      evolutionary relatedness and homoplasmy of mtDNAs that confer elevated risk for a
      late-onset disease contrast strikingly with the distant relatedness and
      heteroplasmy of mitochondrial genomes that cause early-onset disease. The
      dichotomy can be explained by a lack of selection against mutations that confer a
      phenotype at advanced age during most of the evolution of humans. We estimate
      that approximately 1.5 million Caucasians in the United States bear the 4336G
      mutation and are at significantly increased risk of developing mitochondrial AD
      in their lifetime. A mechanism for 4336G-mediated cell death is proposed.

PMID- 7624340
TI  - Expression of a flower-specific Myb protein in leaf cells using a viral vector
      causes ectopic activation of a target promoter.
AB  - The promoter of the bean PAL2 gene (encoding phenylalanine ammonia-lyase; EC
      4.3.1.5) is a model for studies of tissue-restricted gene expression in plants.
      Petal epidermis is one of the tissues in which this promoter is activated in
      tobacco. Previous work suggested that a major factor establishing the pattern of
      PAL2 expression in tobacco petals is the tissue distribution of a protein closely
      related to Myb305, which is a Myb-like transcriptional activator from snapdragon.
      In the present work, we show that Myb305 expression in tobacco leaves causes
      ectopic activation of the PAL2 promoter. To achieve Myb305 expression in planta,
      a viral expression vector was used. This approach combines the utility of
      transient assays with the possibility of direct biochemical detection of the
      introduced factor and may have wider application for studying the function of
      plant transcription factors.

PMID- 7624341
TI  - Three-dimensional functional magnetic resonance imaging of human brain on a
      clinical 1.5-T scanner.
AB  - Functional magnetic resonance imaging (fMRI) is a tool for mapping brain function
      that utilizes neuronal activity-induced changes in blood oxygenation. An
      efficient three-dimensional fMRI method is presented for imaging brain activity
      on conventional, widely available, 1.5-T scanners, without additional hardware.
      This approach uses large magnetic susceptibility weighting based on the echo
      shifting principle combined with multiple gradient echoes per excitation. Motor
      stimulation, induced by self-paced finger tapping, reliably produced significant
      signal increase in the hand region of the contralateral primary motor cortex in
      every subject tested.

PMID- 7624342
TI  - Chlamydia pneumoniae (TWAR) in coronary arteries of young adults (15-34 years
      old).
AB  - An association of Chlamydia pneumoniae with atherosclerosis of coronary and
      carotid arteries and aorta has been found by seroepidemiology and by
      demonstration of the organism in atheromata. Age-matched control tissue from
      persons without atherosclerosis was usually not available. We studied autopsy
      tissue from young persons, many with no atherosclerosis, to determine whether C.
      pneumoniae is present in atheroma in young persons with early atherosclerosis and
      to compare the findings in age- and sex-matched persons without atherosclerosis.
      A left anterior descending coronary artery sample, formalin-fixed, from 49
      subjects, 15-34 years of age, from the multicenter study called Pathobiological
      Determinants of Atherosclerosis in Youth (PDAY), was examined by
      immunocytochemistry and the polymerase chain reaction (PCR) for the presence of
      C. pneumoniae and by PCR for cytomegalovirus. A hematoxylin/eosin-stained section
      was used to determine disease present in the studied sample. Seven of the artery
      samples were found to have atheromatous plaque, 11 had intimal thickening, and 31
      had no lesions. Eight of the samples were positive for C. pneumoniae by
      immunocytochemistry (n = 7) and/or PCR (n = 3). Six of the 7 (86%) atheroma, 2 of
      the 11 (18%) with intimal thickening, and none of the 31 normal-appearing
      coronary samples were positive. Four were positive by PCR for cytomegalovirus, 2
      from diseased arteries and 2 from normal arteries. Examination of the adjacent
      left coronary artery sample with a fat stain found abnormalities in 25 of the
      patients, but 19 still showed no evidence of atherosclerosis as a result of
      either examination. Thus, C. pneumoniae is found in coronary lesions in young
      adults with atherosclerosis but is not found in normal-appearing coronary
      arteries of both persons with and without other evidence of atherosclerosis.

PMID- 7624343
TI  - STAT3 activation by cytokines utilizing gp130 and related transducers involves a
      secondary modification requiring an H7-sensitive kinase.
AB  - Ciliary neurotrophic factor, oncostatin M, leukemia-inhibitory factor, and
      interleukin 6 are related cytokines that initiate signaling by homodimerizing the
      signal-transducing receptor component gp130 or by heterodimerizing gp130 with a
      gp130-related receptor component. Receptor dimerization in turn activates
      receptor-associated kinases of the Jak/Tyk family, resulting in the rapid
      tyrosine phosphorylation of several intracellular proteins, including those of
      two members of the signal transducers and activators of transcription (STAT)
      family--STAT1 and STAT3. Here we show that all cytokines that utilize gp130
      sequentially induce two distinct forms of STAT3 in all responding cells examined,
      with the two forms apparently differing because of a time-dependent secondary
      serine/threonine phosphorylation involving an H7-sensitive kinase. While both
      STAT3 forms bind DNA and translocate to the nucleus, the striking time-dependent
      progression from one form to the other implies other important functional
      differences between the two forms. Granulocyte colony-stimulating factor, which
      utilizes a receptor highly related to gp130, also induces these two forms of
      STAT3. In contrast to a number of other cytokines and growth factors, all
      cytokines using gp130 and related signal transducers consistently and
      preferentially induce the two forms of STAT3 as compared with STAT1; this
      characteristic STAT activation pattern is seen regardless of which Jak/Tyk
      kinases are used in a particular response, consistent with the notion that the
      receptor components themselves are the primary determinants of which STATs are
      activated.

PMID- 7624344
TI  - Crystal and molecular structure of paclitaxel (taxol).
AB  - Paclitaxel (formerly called taxol), an important anticancer drug, inhibits cell
      replication by binding to and stabilizing microtubule polymers. As drug-receptor
      interactions are governed by the three-dimensional stereochemistries of both
      participants, we have determined the crystal structure of paclitaxel to identify
      its conformational preferences that may be related to biological activity. The
      monoclinic crystals contain two independent paclitaxel molecules in the
      asymmetric unit plus several water and dioxane solvent molecules. Taxane ring
      conformation is very similar in both paclitaxel molecules and is similar to the
      taxane ring conformation found in the crystal structure of the paclitaxel
      analogue docetaxel (formerly called taxotere). The two paclitaxel molecules have
      carbon-13 side-chain conformations that differ from each other and from that of
      the corresponding side chain in the docetaxel crystal structure. The carbon-13
      side-chain conformation of one paclitaxel molecule is similar to what was
      proposed from NMR studies done in polar solvents, while that of the other
      paclitaxel molecule is different and hitherto unobserved. The paclitaxel
      molecules interact with each other and with solvent atoms through an extensive
      network of hydrogen bonds. Analysis of the hydrogen-bonding network together with
      structure-activity studies may suggest which atoms of paclitaxel are important
      for binding to microtubule receptors.

PMID- 7624345
TI  - Complex formation in yeast double-strand break repair: participation of Rad51,
      Rad52, Rad55, and Rad57 proteins.
AB  - The repair of DNA double-strand breaks in Saccharomyces cerevisiae requires genes
      of the RAD52 epistasis group, of which RAD55 and RAD57 are members. Here, we show
      that the x-ray sensitivity of rad55 and rad57 mutant strains is suppressible by
      overexpression of RAD51 or RAD52. Virtually complete suppression is provided by
      the simultaneous overexpression of RAD51 and RAD52. This suppression occurs at 23
      degrees C, where these mutants are more sensitive to x-rays, as well as at 30
      degrees C and 36 degrees C. In addition, a recombination defect of rad55 and
      rad57 mutants is similarly suppressed. Direct in vivo interactions between the
      Rad51 and Rad55 proteins, and between Rad55 and Rad57, have also been identified
      by using the two-hybrid system. These results indicate that these four proteins
      constitute part of a complex, a "recombinosome," to effect the recombinational
      repair of double-strand breaks.

PMID- 7624347
TI  - Inactivation of simian immunodeficiency virus by hydrostatic pressure.
AB  - The inactivation of the simian immunodeficiency viruses SIVmac251 and SIVagm by
      pressures of 150 and 250 MPa was determined. The extent of inactivation depended
      on the time that the virus was subjected to compression as well as the level of
      the pressure and at 150 Mpa reached 5 log10 dilution units after approximately 10
      hr. The inactivations, which were uniformly carried out at room temperature, were
      independent of the concentration of the virus. Possible applications of pressure
      inactivation for molecular biological and clinical use are discussed.

PMID- 7624346
TI  - Identification of human granzyme B promoter regulatory elements interacting with
      activated T-cell-specific proteins: implication of Ikaros and CBF binding sites
      in promoter activation.
AB  - Granzyme B serine protease is found in the granules of activated cytotoxic T
      cells and in natural and lymphokine-activated killer cells. This protease plays a
      critical role in the rapid induction of target cell DNA fragmentation. The DNA
      regulatory elements that are responsible for the specificity of granzyme B gene
      transcription in activated T-cells reside between nt -148 and +60 (relative to
      the transcription start point at +1) of the human granzyme B gene promoter. This
      region contains binding sites for the transcription factors Ikaros, CBF, Ets, and
      AP-1. Mutational analysis of the human granzyme B promoter reveals that the
      Ikaros binding site (-143 to -114) and the AP-1/CBF binding site (-103 to -77)
      are essential for the activation of transcription in phytohemagglutinin-activated
      peripheral blood lymphocytes, whereas mutation of the Ets binding site does not
      affect promoter activity in these cells.

PMID- 7624348
TI  - Amperometric detection of stimulus-induced quantal release of catecholamines from
      cultured superior cervical ganglion neurons.
AB  - Amperometry has been used for real-time electrochemical detection of the quantal
      release of catecholamines and indolamines from secretory granules in chromaffin
      and mast cells. Using improved-sensitivity carbon fiber electrodes, we now report
      the detection of quantal catecholamine release at the surface of somas of
      neonatal superior cervical ganglion neurons that are studded with axon
      varicosities containing synaptic vesicles. Local application of a bath solution
      containing high K+ or black widow spider venom, each of which greatly enhances
      spontaneous quantal release of transmitter at synapses, evoked barrages of small
      amplitude (2-20 pA), short-duration (0.5-2 ms) amperometric quantal "spikes". The
      median spike charge was calculated as 11.3 fC. This figure corresponds to 3.5 x
      10(4) catecholamine molecules per quantum of release, or approximately 1% that
      evoked by the discharge of the contents of a chromaffin granule.

PMID- 7624349
TI  - Appearance of insulin-like growth factor mRNA in the liver and pyloric ceca of a
      teleost in response to exogenous growth hormone.
AB  - Augmentation of vertebrate growth by growth hormone (GH) is primarily due to its
      regulation of insulin-like growth factor I (IGF I) and IGF II levels. To
      characterize the effect of GH on the levels of IGF I and IGF II mRNA in a
      teleost, 10 micrograms of bovine GH (bGH) per g of body weight was administered
      to juvenile rainbow trout (Oncorhynchus mykiss) through i.p. injection. The
      levels of IGF I and IGF II mRNA were determined simultaneously, by using RNase
      protection assays, in the liver, pyloric ceca, kidney, and gill at 0, 1, 3, 6,
      12, 24, 48, and 72 hr after injection. In the liver, IGF I mRNA levels were
      significantly elevated at 6 and 12 hr (approximately 2- to 3-fold, P < or =
      0.01), while IGF II mRNA levels were significantly elevated at 3 and 6 hr
      (approximately 3-fold, P < or = 0.01). In the pyloric ceca, IGF II mRNA levels
      were significantly elevated at 12, 24, and 48 hr (approximately 3-fold, P < or =
      0.01), while IGF I mRNA was below the limits of assay accuracy. GH-dependent IGF
      mRNA appearance was not detected in the gill and kidney. Serum bGH levels,
      determined by using a radioimmunoassay, were significantly elevated at 3 and 6 hr
      (P < 0.005). In primary hepatocyte culture, IGF I and IGF II mRNA levels
      increased in a bGH dose-dependent fashion, with ED50 values of approximately 45
      and approximately 6 ng of bGH per ml, respectively. The GH-dependent appearance
      of IGF II mRNA in the liver and pyloric ceca suggests important roles for this
      peptide hormone exclusive of IGF I.

PMID- 7624350
TI  - Prolonged survival of pancreatic islet allografts mediated by adenovirus
      immunoregulatory transgenes.
AB  - The adenovirus (Ad) early region 3 (E3) genes code for at least four proteins
      that inhibit the host immune responses mediated by cytotoxic T lymphocytes and
      tumor necrosis factor alpha. To evaluate the potential use of these
      immunoregulatory viral functions in facilitating allogeneic cell transplantation,
      the Ad E3 genes were expressed in pancreatic beta cells in transgenic mice under
      control of the rat insulin II promoter. Transgenic H-2b/d (C57BL/6 x BALB/c)
      islets, expressing the Ad E3 genes, remained viable for at least 94 days after
      transplantation under the kidney capsule of BALB/c (H-2d) recipients.
      Nontransgenic H-2b/d control islets were rejected as anticipated between 14 and
      28 days. Histological analysis of the transplanted transgenic islets revealed
      normal architecture. Immunohistochemical studies with antisera to islet hormones
      revealed the presence of both beta and non-beta islet cells, suggesting a
      propagation of the immunosuppressive effect of Ad proteins from beta cells to
      other islet cells. The use of viral genes, which have evolved to regulate virus
      host interactions, to immunosupress the anti-genicity of donor transplant tissue
      suggests additional ways for prolonging allograft survival. In addition, these
      findings have implications for designing Ad vectors for gene therapy.

PMID- 7624351
TI  - Activin A inhibits Pax-6 expression and perturbs cell differentiation in the
      developing spinal cord in vitro.
AB  - We have developed an in vitro model of the isolated chicken neural plate. Here we
      demonstrate that even in the absence of notochord, the neural plate rapidly
      develops a typical dorsoventral patterning. This observation suggests that the
      ventral cell types are specified or at least predetermined prior to notochord
      formation and that permissive conditions are sufficient for differentiation of
      ventral structures. Treatment of the neural plate with activin A extinguishes Pax
      6 gene expression, whereas the dorsal markers Pax-3 and Pax-7 are still
      expressed. The absence of Pax-6 transcripts can be correlated with an impeded
      differentiation of the motor neurons, whereas the floor plate seems to be
      enlarged. We propose that the region-specific expression of Pax-6 in the spinal
      cord is under the control of activin-like molecules.

PMID- 7624353
TI  - Preferential expansion and survival of B lymphocytes based on VH framework 1 and
      framework 3 expression: "positive" selection in appendix of normal and VH-mutant
      rabbits.
AB  - B cells with a rearranged heavy-chain variable region VHa allotype-encoding VH1
      gene segment predominate throughout the life of normal rabbits and appear to be
      the source of the majority of serum immunoglobulins, which thus bear VHa
      allotypes. The functional role(s) of these VH framework region (FR) allotypic
      structures has not been defined. We show here that B cells expressing surface
      immunoglobulin with VHa2 allotypic specificities are preferentially expanded and
      positively selected in the appendix of young rabbits. By flow cytometry, a higher
      proportion of a2+ B cells were progressing through the cell cycle (S/G2/M)
      compared to a2- B cells, most of which were in the G1/G0 phase of the cell cycle.
      The majority of appendix B cells in dark zones of germinal centers of normal 6
      week-old rabbits were proliferating and very little apoptosis were observed. In
      contrast, in 6-week-old VH-mutant ali/ali rabbits, little cell proliferation and
      extensive apoptosis were observed. Nonetheless even in the absence of VH1, B
      cells with a2-like surface immunoglobulin had developed and expanded in the
      appendix of 11-week-old mutants. The numbers and tissue localization of B cells
      undergoing apoptosis then appeared similar to those found in 6-week-old normal
      appendix. Thus, B cells with immunoglobulin receptors lacking the VHa2 allotypic
      structures were less likely to undergo clonal expansion and maturation. These
      data suggest that "positive" selection of B lymphocytes through FR1 and FR3 VHa
      allotypic structures occurs during their development in the appendix.

PMID- 7624352
TI  - Increased expression in adipocytes of ob RNA in mice with lesions of the
      hypothalamus and with mutations at the db locus.
AB  - The gene product of the recently cloned mouse obese gene (ob) is important in
      regulating adipose tissue mass. ob RNA is expressed specifically by mouse
      adipocytes in vivo in each of several different fat cell depots, including brown
      fat. ob RNA is also expressed in cultured 3T3-442A preadipocyte cells that have
      been induced to differentiate. Mice with lesions of the hypothalamus, as well as
      mice mutant at the db locus, express a 20-fold higher level of ob RNA in adipose
      tissue. These data suggest that both the db gene and the hypothalamus are
      downstream of the ob gene in the pathway that regulates adipose tissue mass and
      are consistent with previous experiments suggesting that the db locus encodes the
      ob receptor. In db/db and lesioned mice, quantitative differences in expression
      level of ob RNA correlated with adipocyte lipid content. The molecules that
      regulate expression level of the ob gene in adipocytes probably are important in
      determining body weight, as are the molecules that mediate the effects of ob at
      its site of action.

PMID- 7624354
TI  - Expression of 5-lipoxygenase in differentiating human skin keratinocytes.
AB  - We studied the expression of arachidonate 5-lipoxygenase (5-LO) in a cell line of
      human keratinocytes (HaCaT) and in normal human skin keratinocytes in tissue
      culture. In undifferentiated keratinocytes 5-LO gene expression was low or
      undetectable as determined by 5-LO mRNA, protein, cell-free enzyme activity, and
      leukotriene production in intact cells. However, after shift to culture
      conditions that promote conversion of prokeratinocytes into a more differentiated
      phenotype, 5-LO gene expression was markedly induced in HaCaT cells and, to a
      lesser extent, in normal keratinocytes. These results show that 5-LO gene
      expression is an intrinsic property of human skin keratinocytes.

PMID- 7624355
TI  - Preparation and properties of nido-carborane-specific monoclonal antibodies for
      potential use in boron neutron capture therapy for cancer.
AB  - As the first step of a research program aimed at developing a bispecific
      monoclonal antibody system for the delivery of boron-rich molecules to tumor
      cells for boron neutron capture therapy, monoclonal antibodies (mAbs) were
      produced against an anionic nido-carborane derivative, 4-[7,8
      dicarbadodecahydroundecaborat(-1)-7-yl]butanoic acid. Two IgG subclass mAbs,
      designated HAW101 and HAW102, were identified that specifically bound the anionic
      nido-carborane hapten, as well as a variety of other anionic nido-carborane cage
      derivatives. By using surface plasmon resonance technology, the affinity
      constants of HAW101 and HAW102 were determined to be 1.9 x 10(9) and 6.8 x 10(8)
      M-1, respectively. A diverse array of 7-substituted and 7,8-disubstituted anionic
      nido-carborane derivatives reacted with the mAb HAW101 in competition ELISA,
      whereas anionic closo-polyhedral boranes showed negligible binding, suggesting a
      role for the open nido-carborane cage structure. These results suggest that mAbs
      such as HAW101, which bind anionic nido-carboranes, are useful in the development
      of bispecific mAbs for specific targeting and enhanced boron delivery to tumor
      sites.

PMID- 7624356
TI  - Conditional site-specific recombination in mammalian cells using a ligand
      dependent chimeric Cre recombinase.
AB  - We have developed a strategy to generate mutant genes in mammalian cells in a
      conditional manner by employing a fusion protein, Cre-ER, consisting of the loxP
      site-specific Cre recombinase linked to the ligand-binding domain of the human
      estrogen receptor. We have established homozygous retinoid X receptor alpha
      negative (RXR alpha-/-) F9 embryonal carcinoma cells constitutively expressing
      Cre-ER and have shown that estradiol or the estrogen agonist/antagonist 4
      hydroxytamoxifen efficiently induced the recombinase activity, whereas no
      activity was detected in the absence of ligand or in the presence of the
      antiestrogen ICI 164,384. Furthermore, using a targeting vector containing a
      selection marker flanked by loxP sites, we have inactivated one retinoic acid
      receptor alpha allele in such a line, demonstrating that the presence of the
      recombinase does not inhibit homologous recombination. Combining this conditional
      site-specific recombination system with tissue-specific expression of Cre-ER may
      allow modification of the mammalian genome in vivo in a spatiotemporally
      regulated manner.

PMID- 7624357
TI  - The bacterial colicin active against tumor cells in vitro and in vivo is
      verotoxin 1.
AB  - We have identified verotoxin 1 (VT1) as the active component within an
      antineoplastic bacteriocin preparation from Escherichia coli HSC10 studied over
      two decades. Recombinant VT1 can simulate the toxicity of anticancer proteins
      (ACP), and the antineoplastic activity of ACP (and VT1) was abrogated by
      treatment with anti-VT1 antibody. Similarly, VT1 mimics the protective effect of
      ACP in a murine metastatic fibrosarcoma model. Prior immunization with VT1 B
      subunit prevents the effect of VT1 or ACP in this model. The activity of ACP
      against a variety of human ovarian cell lines was mimicked by VT1, and multidrug
      resistant variants were significantly hypersensitive. Primary ovarian tumors and
      metastases contain elevated levels of globotriaosylceramide compared with normal
      ovaries, and overlay of frozen tumor sections showed selective VT binding to
      tumor tissue and the lumen of invading blood vessels. Our contention that VT1
      could provide an additional approach to the management of certain human neoplasms
      is discussed.

PMID- 7624358
TI  - Design and biological activities of L-163,191 (MK-0677): a potent, orally active
      growth hormone secretagogue.
AB  - A potent, orally active growth hormone (GH) secretagogue L-163,191 belonging to a
      recently synthesized structural class has been characterized. L-163,191 releases
      GH from rat pituitary cells in culture with EC50 = 1.3 +/- 0.09 nM and is
      mechanistically indistinguishable from the GH-releasing peptide GHRP-6 and the
      prototypical nonpeptide GH secretagogue L-692,429 but clearly distinguishable
      from the natural GH secretagogue, GH-releasing hormone. L-163,191 elevates GH in
      dogs after oral doses as low as 0.125 mg/kg and was shown to be specific in its
      release of GH without significant effect on plasma levels of aldosterone,
      luteinizing hormone, thyroxine, and prolactin after oral administration of 1
      mg/kg. Only modest increases in cortisol were observed. Based on these
      properties, L-163,191 has been selected for clinical studies.

PMID- 7624359
TI  - kappa-Opioid receptor in humans: cDNA and genomic cloning, chromosomal
      assignment, functional expression, pharmacology, and expression pattern in the
      central nervous system.
AB  - Using the mouse delta-opioid receptor cDNA as a probe, we have isolated genomic
      clones encoding the human mu- and kappa-opioid receptor genes. Their organization
      appears similar to that of the human delta receptor gene, with exon-intron
      boundaries located after putative transmembrane domains 1 and 4. The kappa gene
      was mapped at position q11-12 in human chromosome 8. A full-length cDNA encoding
      the human kappa-opioid receptor has been isolated. The cloned receptor expressed
      in COS cells presents a typical kappa 1 pharmacological profile and is negatively
      coupled to adenylate cyclase. The expression of kappa-opioid receptor mRNA in
      human brain, as estimated by reverse transcription-polymerase chain reaction, is
      consistent with the involvement of kappa-opioid receptors in pain perception,
      neuroendocrine physiology, affective behavior, and cognition. In situ
      hybridization studies performed on human fetal spinal cord demonstrate the
      presence of the transcript specifically in lamina II of the dorsal horn. Some
      divergences in structural, pharmacological, and anatomical properties are noted
      between the cloned human and rodent receptors.

PMID- 7624360
TI  - Leukocytes express connexin 43 after activation with lipopolysaccharide and
      appear to form gap junctions with endothelial cells after ischemia-reperfusion.
AB  - Levels and subcellular distribution of connexin 43 (Cx43), a gap junction
      protein, were studied in hamster leukocytes before and after activation with
      endotoxin (lipopolysaccharide, LPS) both in vitro and in vivo. Untreated
      leukocytes did not express Cx43. However, Cx43 was clearly detectable by indirect
      immunofluorescence in cells treated in vitro with LPS (1 micrograms/ml, 3 hr).
      Cx43 was also detected in leukocytes obtained from the peritoneal cavity 5-7 days
      after LPS-induced inflammation. In some leukocytes that formed clusters Cx43
      immunoreactivity was present at appositional membranes, suggesting formation of
      homotypic gap junctions. In cell homogenates of activated peritoneal macrophages,
      Cx43, detected by Western blot analysis, was mostly unphosphorylated. A second in
      vivo inflammatory condition studied was that induced by ischemia-reperfusion of
      the hamster cheek pouch. In this system, leukocytes that adhered to venular
      endothelial cells after 1 hr of ischemia, followed by 1 hr of reperfusion,
      expressed Cx43. Electron microscope observations revealed small close
      appositions, putative gap junctions, at leukocyte-endothelial cell and leukocyte
      leukocyte contacts. These results indicate that the expression of Cx43 can be
      induced in leukocytes during an inflammatory response which might allow for
      heterotypic or homotypic intercellular gap junctional communication. Gap
      junctions may play a role in leukocyte extravasation.

PMID- 7624361
TI  - De novo decorin gene expression suppresses the malignant phenotype in human colon
      cancer cells.
AB  - The rapid progress in the cloning of proteoglycan genes has enabled investigators
      to examine in depth the functional roles these polyhedric molecules play in the
      control of cell proliferation. Decorin, a leucine-rich proteoglycan expressed by
      most connective tissues, is a prototype molecule that regulates cellular growth
      via two mechanisms: modulation of growth factor activity and matrix assembly. We
      now provide direct evidence that human colon cancer cells stably transfected with
      decorin cDNA exhibit a marked suppression of the transformed phenotype: the cells
      have a reduced growth rate in vitro, form small colonies in soft agar, and do not
      generate tumors in scid/scid mice. Several independent clones are arrested in the
      G1 phase of the cell cycle, and their growth suppression can be restored by
      treatment with decorin antisense oligodeoxynucleotides. These effects are
      independent of growth factors and are not due to either clonal selection or
      integration site of the decorin gene. These findings correlate well with the
      observation that decorin gene expression is markedly up-regulated during
      quiescence. Decorin thus appears to be one component of a negative loop that
      controls cell growth.

PMID- 7624362
TI  - A small bispecific antibody construct expressed as a functional single-chain
      molecule with high tumor cell cytotoxicity.
AB  - Construction of a bispecific single-chain antibody derivative is described that
      consists of two different single-chain Fv fragments joined through a Gly-Ser
      linker. One specificity of the two Fv fragments is directed against the CD3
      antigen of human T cells and the other is directed against the epithelial 17-1A
      antigen; the latter had been found in a clinical trial to be a suitable target
      for antibody therapy of minimal residual colorectal cancer. The construct could
      be expressed in CHO cells as a fully functional protein, while its periplasmic
      expression in Escherichia coli resulted in a nonfunctional protein only. The
      antigen-binding properties of the bispecific single-chain antibody are
      indistinguishable from those of the corresponding univalent single-chain Fv
      fragments. By redirecting human peripheral T lymphocytes against 17-1A-positive
      tumor cells, the bispecific antibody proved to be highly cytotoxic at nanomolar
      concentrations as demonstrated by 51Cr release assay on various cell lines. The
      described bispecific construct has a molecular mass of 60 kDa and can be easily
      purified by its C-terminal histidine tail on a Ni-NTA chromatography column. As
      bispecific antibodies have already been shown to be effective in vivo in
      experimental tumor systems as well as in phase-one clinical trials, the small
      CD3/17-1A-bispecific antibody may be more efficacious than intact antibodies
      against minimal residual cancer cells.

PMID- 7624363
TI  - Structure and function of a human transcription factor TFIIIB subunit that is
      evolutionarily conserved and contains both TFIIB- and high-mobility-group protein
      2-related domains.
AB  - Transcription factor TFIIIB plays a central role in transcription initiation by
      RNA polymerase III on genes encoding tRNA, 5S rRNA, and other small structural
      RNAs. We report the purification of a human TFIIIB-derived complex containing
      only the TATA-binding polypeptide (TBP) and a 90-kDa subunit (TFIIIB90) and the
      isolation of a cDNA clone encoding the 90-kDa subunit. The N-terminal half of
      TFIIIB90 exhibits sequence similarity to the yeast TFIIIB70 (BRF) and the class
      II transcription factor TFIIB and interacts weakly with TBP. The C-terminal half
      of TFIIIB90 contains a high-mobility-group protein 2 (HMG2)-related domain and
      interacts strongly with TBP. Recombinant TFIIIB90 plus recombinant human TBP
      substitute for human TFIIIB in a complementation assay for transcription of 5S,
      tRNA, and VA1 RNA genes, and both the TFIIB-related domain and the HMG2-related
      domain are required for this activity. TFIIIB90 is also required for
      transcription of human 7SK and U6 RNA genes by RNA polymerase III, but apparently
      within a complex distinct from the TBP/TFIIIB90 complex.

PMID- 7624364
TI  - Expression cloning of a human polysialyltransferase that forms the polysialylated
      neural cell adhesion molecule present in embryonic brain.
AB  - Polysialic acid is a developmentally regulated posttranslational modification of
      the neural cell adhesion molecule (N-CAM). It has been suggested that this large
      anionic carbohydrate modulates the adhesive property of N-CAM, but the precise
      function of polysialic acid is not known. Here we describe the isolation and
      functional expression of a cDNA encoding a human polysialyltransferase. For this
      expression cloning, COS-1 cells were cotransfected with a human fetal brain cDNA
      library and a cDNA encoding human N-CAM. Transfected COS-1 cells were stained
      with a monoclonal antibody specific for polysialic acid and enriched by
      fluorescence-activated cell sorting. Sibling selection of recovered plasmids
      resulted in a cDNA clone that directs the expression of polysialic acid on the
      cell surface. The deduced amino acid sequence indicates that the
      polysialyltransferase shares a common sequence motif with other
      sialyltransferases cloned so far. The polysialyltransferase is, however, distinct
      by having two clusters of basic amino acids. The amount of the
      polysialyltransferase transcripts correlates well with the formation of
      polysialic acid in various human tissues, and is abundant in the fetal brain but
      not in the adult brain. Moreover, HeLa cells stably expressing polysialic acid
      and N-CAM promoted neurite outgrowth and sprouting. These results indicate that
      the cloned polysialyltransferase forms polysialylated, embryonic N-CAM, which is
      critical for plasticity of neural cells.

PMID- 7624365
TI  - Green fluorescent protein as a vital marker and reporter of gene expression in
      Drosophila.
AB  - We have used the green fluorescent protein (GFP) from the jellyfish Aequorea
      victoria as a vital marker/reporter in Drosophila melanogaster. Transgenic flies
      were generated in which GFP was expressed under the transcriptional control of
      the yeast upstream activating sequence that is recognized by GAL4. These flies
      were crossed to several GAL4 enhancer trap lines, and expression of GFP was
      monitored in a variety of tissues during development using confocal microscopy.
      Here, we show that GFP could be detected in freshly dissected ovaries, imaginal
      discs, and the larval nervous system without prior fixation or the addition of
      substrates or antibodies. We also show that expression of GFP could be monitored
      in intact living embryos and larvae and in cultured egg chambers, allowing us to
      visualize dynamic changes in gene expression during real time.

PMID- 7624367
TI  - Image processing via level set curvature flow.
AB  - We present a controlled image smoothing and enhancement method based on a
      curvature flow interpretation of the geometric heat equation. Compared to
      existing techniques, the model has several distinct advantages. (i) It contains
      just one enhancement parameter. (ii) The scheme naturally inherits a stopping
      criterion from the image; continued application of the scheme produces no further
      change. (iii) The method is one of the fastest possible schemes based on a
      curvature-controlled approach.

PMID- 7624366
TI  - A splice variant of alpha 6 integrin is associated with malignant conversion in
      mouse skin tumorigenesis.
AB  - The epithelial-specific integrin alpha 6 beta 4 is suprabasally expressed in
      benign skin tumors (papillomas) and is diffusely expressed in carcinomas
      associated with an increase in the proliferating compartment. Analysis of RNA
      samples by reverse transcriptase-PCR and DNA sequencing revealed that chemically
      or oncogenically induced papillomas (n = 8) expressed a single transcript of the
      alpha 6 subunit, identified as the alpha 6 A splice variant. In contrast,
      carcinomas (n = 13) expressed both alpha 6A and an alternatively spliced form,
      alpha 6B. Primary keratinocytes and a number of keratinocyte cell lines that vary
      in biological potential from normal skin, to benign papillomas, to well
      differentiated slowly growing carcinomas exclusively expressed alpha 6A. However,
      I7, an oncogene-induced cell line that produces highly invasive carcinomas,
      expressed both alpha 6A and alpha 6B transcript and protein. The expression of
      alpha 6B in I7 cells was associated with increased attachment to a laminin matrix
      compared to cell lines exclusively expressing alpha 6A. Furthermore, introduction
      of an alpha 6B expression vector into a papilloma cell line expressing alpha 6A
      increased laminin attachment. When a papilloma cell line was converted to an
      invasive carcinoma by introduction of the v-fos oncogene, the malignant cells
      expressed both alpha 6A and alpha 6B, while the parent cell line and cells
      transduced with v-jun or c-myc, which retained the papilloma phenotype, expressed
      only alpha 6A. Comparative analysis of alpha 6B expression in cell lines and
      their derived tumors indicate that alpha 6B transcripts are more abundant in
      tumors than cell lines, and alpha 6B is expressed to a greater extent in poorly
      differentiated tumors. These results establish a link between malignant
      conversion and invasion of squamous tumor cells and the regulation of transcript
      processing of the alpha 6 beta 4 integrin.

PMID- 7624368
TI  - Enhancer-dependent interaction between 5' and 3' splice sites in trans.
AB  - Splice-site selection and alternative splicing of nuclear pre-mRNAs can be
      controlled by splicing enhancers that act by promoting the activity of upstream
      splice sites. Here we show that RNA molecules containing a 3' splice site and
      enhancer sequence are efficiently spliced in trans to RNA molecules containing
      normally cis-spliced 5' splice sites or to normally trans-spliced spliced leader
      RNAs from lower eukaryotes. In addition, we show that this reaction is stimulated
      by (Ser + Arg)-rich splicing factors that are known to promote protein-protein
      interactions in the cis-splicing reaction. Thus, splicing enhancers facilitate
      the assembly of protein complexes on RNAs containing a 3' splice site, and this
      complex is sufficiently stable to functionally interact with 5' splice sites
      located on separate RNAs. This trans-splicing is mediated by interactions between
      (Ser + Arg)-rich splicing factors bound to the enhancer and general splicing
      factors bound to the 5' and 3' splice sites. These same interactions are likely
      to play a crucial role in alternative splicing and splice-site selection in cis.

PMID- 7624369
TI  - High-affinity binding sites for histone H1 in plasmid DNA.
AB  - The interaction of histone H1 isolated from chicken erythrocytes with restriction
      fragments from plasmids pBR322 and pUC19 was studied by gel electrophoresis.
      Certain restriction fragments exhibited unusually high affinity for the histone,
      forming high molecular mass complexes at protein to DNA ratios at which the other
      fragments did not show evidence for binding. The highly preferred fragments are
      intrinsically curved, as judged by their electrophoretic mobility in
      polyacrylamide gels, by computer modeling, and by imaging with scanning force
      microscopy. However, control experiments with either curved portions of the same
      fragments or highly curved kinetoplast DNA fragments showed that the presence of
      curvature alone was not sufficient for preferential binding. By using various
      restriction fragments centered around the highly preferred sequence, it was found
      that the high-affinity binding required in addition the presence of specific
      sequences on both sides of the region of curvature. Thus, both curvature and the
      presence of specific sites seem to be required to generate high affinity.

PMID- 7624371
TI  - Dynamics of maize endosperm development and DNA endoreduplication.
AB  - Endosperm development in Zea mays is characterized by a period of intense mitotic
      activity followed by a period in which mitosis is essentially eliminated and the
      cell cycle becomes one of alternating S and G phases, leading to
      endoreduplication of the nuclear DNA. The endosperm represents a significant
      contribution to the grain yield of maize; thus, methods that facilitate the study
      of cellular kinetics may be useful in discerning cellular and molecular
      components of grain yield. Two mathematical models have been developed to
      describe the kinetics of endosperm growth. The first describes the kinetics of
      mitosis during endosperm development; the second describes the kinetics of DNA
      endoreduplication during endosperm development. The mitotic model is a
      modification of standard growth curves. The endoreduplication model is composed
      of six differential equations that represent the progression of nuclei from one
      DNA content to another during the endoreduplication process. Total nuclei number
      per endosperm and the number of 3C, 6C, 12C, 24C, 48C, and 96C nuclei per
      endosperm (C is the haploid DNA content per nucleus) for inbred W64A from 8 to 18
      days after pollination were determined by flow cytometry. The results indicate
      that the change in number of nuclei expressed as a function of the number of days
      after pollination is the same from one yearly crop to another. These data were
      used in the model to determine the endosperm growth rate, the maximum nuclei
      number per endosperm, and transition rates from one C value to the next higher C
      value. The kinetics of endosperm development are reasonably well represented by
      the models. Thus, the models provide a means to quantify the complex pattern of
      endosperm development.

PMID- 7624370
TI  - Evidence that the 50-kDa substrate of brefeldin A-dependent ADP-ribosylation
      binds GTP and is modulated by the G-protein beta gamma subunit complex.
AB  - Brefeldin A, a fungal metabolite that inhibits membrane transport, induces the
      mono(ADP-ribosyl)ation of two cytosolic proteins of 38 and 50 kDa as judged by
      SDS/PAGE. The 38-kDa substrate has been previously identified as glyceraldehyde-3
      phosphate dehydrogenase (GAPDH). We report that the 50-kDa BFA-induced ADP
      ribosylated substrate (BARS-50) has native forms of 170 and 130 kDa, as
      determined by gel filtration of rat brain cytosol, indicating that BARS-50 might
      exist as a multimeric complex. BARS-50 can bind GTP, as indicated by blot-overlay
      studies with [alpha-32P]GTP and by photoaffinity labeling with guanosine 5'
      [gamma-32P] [beta,gamma-(4-azidoanilido)]triphosphate. Moreover, ADP-ribosylation
      of BARS-50 was completely inhibited by the beta gamma subunit complex of G
      proteins, while the ADP-ribosylation of GAPDH was unmodified, indicating that
      this effect was due to an interaction of the beta gamma complex with BARS-50,
      rather than with the ADP-ribosylating enzyme. Two-dimensional gel electrophoresis
      and immunoblot analysis shows that BARS-50 is a group of closely related proteins
      that appear to be different from all the known GTP-binding proteins.

PMID- 7624372
TI  - Absence of yolk sac hematopoiesis from mice with a targeted disruption of the scl
      gene.
AB  - The scl gene encodes a basic-helix-loop-helix transcription factor which was
      identified through its involvement in chromosomal translocations in T-cell
      leukemia. To elucidate its physiological role, scl was targeted in embryonic stem
      cells. Mice heterozygous for the scl null mutation were intercrossed and their
      offspring were genotyped. Homozygous mutant (scl-/-) pups were not detected in
      newborn litters, and analysis at earlier time points demonstrated that scl-/-
      embryos were dying around embryonic day 9.5. The scl-/- embryos were pale,
      edematous, and markedly growth retarded after embryonic day 8.75. Histological
      studies showed complete absence of recognizable hematopoiesis in the yolk sac of
      these embryos. Early organogenesis appeared to be otherwise normal. Culture of
      yolk sac cells of wild-type, heterozygous, and homozygous littermates confirmed
      the absence of hematopoietic cells in scl-/- yolk sacs. Reverse transcription PCR
      was used to examine the transcripts of several genes implicated in early
      hematopoiesis. Transcripts of GATA-1 and PU.1 transcription factors were absent
      from RNA from scl-/- yolk sacs and embryos. These results implicate scl as a
      crucial regulator of early hematopoiesis.

PMID- 7624373
TI  - Transformation of mammalian cells by overexpressing H2O2-generating peroxisomal
      fatty acyl-CoA oxidase.
AB  - Peroxisome proliferators induce qualitatively predictable pleiotropic responses,
      including development of hepatocellular carcinomas in rats and mice despite the
      inability of these compounds to interact with and damage DNA directly. In view of
      the nongenotoxic nature of peroxisome proliferators, it has been postulated that
      hepatocarcinogenesis by this class of chemicals is due to a receptor-mediated
      process leading to transcriptional activation of H2O2-generating peroxisomal
      fatty acyl-CoA oxidase (ACOX) in liver. To test this hypothesis, we overexpressed
      rat ACOX in African green monkey kidney cells (CV-1 cells) under control of the
      cytomegalovirus promoter. A stably transfected CV-1 cell line overexpressing rat
      ACOX, designated CV-ACOX4, when exposed to a fatty acid substrate (150 microM
      linoleic acid) for 2-6 weeks, formed transformed foci, grew efficiently in soft
      agar, and developed adenocarcinomas when transplanted into nude mice. These
      findings indicate that sustained overexpression of H2O2-generating ACOX causes
      cell transformation and provide further support for the role of peroxisome
      proliferation in hepatocarcinogenesis induced by peroxisome proliferators.

PMID- 7624374
TI  - Structure of the gene for porcine peptide antibiotic PR-39, a cathelin gene
      family member: comparative mapping of the locus for the human peptide antibiotic
      FALL-39.
AB  - PR-39 is a porcine 39-aa peptide antibiotic composed of 49% proline and 24%
      arginine, with an activity against Gram-negative bacteria comparable to that of
      tetracycline. In Escherichia coli, it inhibits DNA and protein synthesis. PR-39
      was originally isolated from pig small intestine, but subsequent cDNA cloning
      showed that the gene is expressed in the bone marrow. The open reading frame of
      the clone showed that PR-39 is made as 173-aa precursor whose proregion belongs
      to the cathelin family. The PR39 gene, which is rather compact and spans only
      1784 bp has now been sequenced. The coding information is split into four exons.
      The first exon contains the signal sequence of 29 residues and the first 37
      residues of the cathelin propart. Exons 2 and 3 contain only cathelin
      information, while exon 4 codes for the four C-terminal cathelin residues and the
      mature PR-39 peptide extended by three residues. The sequenced upstream region
      (1183 bp) contains four potential recognition sites for NF-IL6 and three for
      APRF, transcription factors known to regulate genes for both cytokines and acute
      phase response factors. Genomic hybridizations revealed a fairly high level of
      restriction fragment length polymorphism and indicated that there are at least
      two copies of the PR39 gene in the pig genome. PR39 was mapped to pig chromosome
      13 by linkage and in situ hybridization mapping. The gene for the human peptide
      antibiotic FALL-39 (also a member of the cathelin family) was mapped to human
      chromosome 3, which is homologous to pig chromosome 13.

PMID- 7624375
TI  - Conserved catalytic machinery and the prediction of a common fold for several
      families of glycosyl hydrolases.
AB  - The regions surrounding the catalytic amino acids previously identified in a few
      "retaining" O-glycosyl hydrolases (EC 3.2.1) have been analyzed by hydrophobic
      cluster analysis and have been used to define sequence motifs. These motifs have
      been found in more than 150 glycosyl hydrolase sequences representing at least
      eight established protein families that act on a large variety of substrates.
      This allows the localization and the precise role of the catalytic residues
      (nucleophile and acid catalyst) to be predicted for each of these enzymes,
      including several lysosomal glycosidases. An identical arrangement of the
      catalytic nucleophile was also found for S-glycosyl hydrolases (myrosinases; EC
      3.2.3.1) for which the acid catalyst is lacking. A (beta/alpha)8 barrel structure
      has been reported for two of the eight families of proteins that have been
      grouped. It is suggested that the six other families also share this fold at
      their catalytic domain. These enzymes illustrate how evolutionary events led to a
      wide diversification of substrate specificity with a similar disposition of
      identical catalytic residues onto the same ancestral (beta/alpha)8 barrel
      structure.

PMID- 7624376
TI  - Identification of a second homolog of N-ethylmaleimide-sensitive fusion protein
      that is expressed in the nervous system and secretory tissues of Drosophila.
AB  - N-Ethylmaleimide-sensitive fusion protein (NSF) is an ATPase known to have an
      essential role in intracellular membrane transport events. Recently, cDNA clones
      encoding a Drosophila melanogaster homolog of this protein, named dNSF, were
      characterized and found to be expressed in the nervous system. We now report the
      identification of a second homolog of NSF, called dNSF-2 within this species and
      report evidence that this ubiquitous and widely utilized fusion protein belongs
      to a multigene family. The predicted amino acid sequence of dNSF-2 is 84.5%
      identical to dNSF (hereafter named dNSF-1), 59% identical to NSF from Chinese
      hamster, and 38.5% identical to the yeast homolog SEC18. The highest similarity
      was found in a region of dNSF-2 containing one of two ATP-binding sites; this
      region is most similar to members of a superfamily of ATPases. dNSF-2 is
      localized to a region between bands 87F12 and 88A3 on chromosome 3, and in situ
      hybridization techniques revealed expression in the nervous system during
      embryogenesis and in several imaginal discs and secretory structures in the
      larvae. Developmental modulation of dNSF-2 expression suggests that quantitative
      changes in the secretory apparatus are important in histogenesis.

PMID- 7624377
TI  - Isolation of multiple sequences from the Plasmodium falciparum genome that encode
      conserved domains homologous to those in erythrocyte-binding proteins.
AB  - Open reading frames in the Plasmodium falciparum genome encode domains homologous
      to the adhesive domains of the P. falciparum EBA-175 erythrocyte-binding protein
      (eba-175 gene product) and those of the Plasmodium vivax and Plasmodium knowlesi
      Duffy antigen-binding proteins. These domains are referred to as Duffy binding
      like (DBL), after the receptor that determines P. vivax invasion of Duffy blood
      group-positive human erythrocytes. Using oligonucleotide primers derived from
      short regions of conserved sequence, we have developed a reverse transcription
      PCR method that amplifies sequences encoding the DBL domains of expressed genes.
      Products of these reverse transcription-PCR amplifications include sequences of
      single-copy genes (including eba-175) and variably transcribed genes that cross
      hybridize to multiple regions of the genome. Restriction patterns of the
      multicopy genes show a high degree of polymorphism among different parasite
      lines, whereas single-copy genes are generally conserved. Characterization of the
      single-copy genes has identified a gene (ebl-1) that is related to eba-175 and is
      likely to be involved in erythrocyte invasion.

PMID- 7624378
TI  - Chronic mitochondrial energy impairment produces selective striatal degeneration
      and abnormal choreiform movements in primates.
AB  - Although the gene defect responsible for Huntington disease (HD) has recently
      been identified, the pathogenesis of the disease remains obscure. One potential
      mechanism is that the gene defect may lead to an impairment of energy metabolism
      followed by slow excitotoxic neuronal injury. In the present study we examined
      whether chronic administration of 3-nitropropionic acid (3-NP), an irreversible
      inhibitor of succinate dehydrogenase, can replicate the neuropathologic and
      clinical features of HD in nonhuman primates. After 3-6 weeks of 3-NP
      administration, apomorphine treatment induced a significant increase in motor
      activity as compared with saline-treated controls. Animals showed both choreiform
      movements, as well as foot and limb dystonia, which are characteristic of HD.
      More prolonged 3-NP treatment in two additional primates resulted in spontaneous
      dystonia and dyskinesia accompanied by lesions in the caudate and putamen seen by
      magnetic resonance imaging. Histologic evaluation showed that there was a
      depletion of calbindin neurons, astrogliosis, sparing of NADPH-diaphorase
      neurons, and growth-related proliferative changes in dendrites of spiny neurons
      similar to changes in HD. The striosomal organization of the striatum and the
      nucleus accumbens were spared. These findings show that chronic administration of
      3-NP to nonhuman primates can replicate many of the characteristic motor and
      histologic features of HD, further strengthening the possibility that a subtle
      impairment of energy metabolism may play a role in its pathogenesis.

PMID- 7624379
TI  - Mapping sites of interaction of p47-phox and flavocytochrome b with random
      sequence peptide phage display libraries.
AB  - During assembly of the phagocyte NADPH oxidase, cytosolic p47-phox translocates
      to the plasma membrane and binds to flavocytochrome b, and binding domains for
      p47-phox have been identified on the C-terminal tails of both flavocytochrome b
      subunits. In the present report, we further examine the interaction of these two
      oxidase components by using random-sequence peptide phage display library
      analysis. Screening p47-phox with the peptide libraries identified five potential
      sites of interaction with flavocytochrome b, including three previously reported
      regions of interaction and two additional regions of interaction of p47-phox with
      gp91-phox and p22-phox. The additional sites were mapped to a domain on the first
      predicted cytosolic loop of gp91-phox encompassing residues S86TRVRRQL93 and to a
      domain near the cytosolic C-terminal tail of gp91-phox encompassing residues
      F450EWFADLL457. The mapping also confirmed a previously reported binding domain
      on gp91-phox (E554SGPRGVHFIF564) and putative Src homology 3 domain binding sites
      on p22-phox (P156PRPP160 and G177GPPGGP183). To demonstrate that the additional
      regions identified were biologically significant, peptides mimicking the gp91
      phox sequences F77LRGSSACCSTRVRRQL93 and E451WFADLLQLLESQ463 were synthesized and
      assayed for their ability to inhibit NADPH oxidase activity. These peptides had
      EC50 values of 1 microM and 230 microM, respectively, and inhibited activation
      when added prior to assembly but did not affect activity of the preassembled
      oxidase. Our data demonstrate the usefulness of phage display library analysis
      for the identification of biologically relevant sites of protein-protein
      interaction and show that the binding of p47-phox to flavocytochrome b involves
      multiple binding sites along the C-terminal tails of both gp91- and p22-phox and
      other regions of gp91-phox nearer to the N terminus.

PMID- 7624382
TI  - Enhancers increase the probability but not the level of gene expression.
AB  - We have studied enhancer function in transient and stable expression assays in
      mammalian cells by using systems that distinguish expressing from nonexpressing
      cells. When expression is studied in this way, enhancers are found to increase
      the probability of a construct being active but not the level of expression per
      template. In stably integrated constructs, large differences in expression level
      are observed but these are not related to the presence of an enhancer. Together
      with earlier studies, these results suggest that enhancers act to affect a binary
      (on/off) switch in transcriptional activity. Although this idea challenges the
      widely accepted model of enhancer activity, it is consistent with much, if not
      all, experimental evidence on this subject. We hypothesize that enhancers act to
      increase the probability of forming a stably active template. When randomly
      integrated into the genome, enhancers may affect a metastable state of
      repression/activity, permitting expression in regions that would not permit
      activity of an isolated promoter.

PMID- 7624381
TI  - Function of the p86 subunit of eukaryotic initiation factor (iso)4F as a
      microtubule-associated protein in plant cells.
AB  - The isozyme form of eukaryotic initiation factor 4F [eIF-(iso)4F] from wheat germ
      is composed of a p28 subunit that binds the 7-methylguanine cap of mRNA and a p86
      subunit having unknown function. The p86 subunit was found to have limited
      sequence similarity to a kinesin-like protein encoded by the katA gene of
      Arabidopsis thaliana. Native wheat germ eIF-(iso)4F and bacterially expressed p86
      subunit and p86-p28 complex bound to taxol-stabilized maize microtubules (MTs) in
      vitro. Binding saturation occurred at 1 mol of p86 per 5-6 mol of polymerized
      tubulin dimer, demonstrating a substoichiometric interaction of p86 with MTs. No
      evidence was found for a direct interaction of the p28 subunit with MTs. Unlike
      kinesin, cosedimentation of eIF-(iso)4F with MTs was neither reduced by MgATP nor
      enhanced by adenosine 5'-[gamma-imido]triphosphate. Both p86 subunit and p86-p28
      complex induced the bundling of MTs in vitro. The p86 subunit was immunolocalized
      to the cytosol in root maize cells and existed in three forms: fine particles,
      coarse particles, and linear patches. Many coarse particles and linear patches
      were colocalized or closely associated with cortical MT bundles in interphase
      cells. The results indicate that the p86 subunit of eIF-(iso)4F is a MT
      associated protein that may simultaneously link the translational machinery to
      the cytoskeleton and regulate MT disposition in plant cells.

PMID- 7624380
TI  - Convergent and parallel activation of low-conductance potassium channels by
      calcium and cAMP-dependent protein kinase.
AB  - K+ channels, which have been linked to regulation of electrogenic solute
      transport as well as Ca2+ influx, represent a locus in hepatocytes for the
      concerted actions of hormones that employ Ca2+ and cAMP as intracellular
      messengers. Despite considerable study, the single-channel basis for synergistic
      effects of Ca2+ and cAMP on hepatocellular K+ conductance is not well understood.
      To address this question, patch-clamp recording techniques were applied to a
      model liver cell line, HTC hepatoma cells. Increasing the cytosolic Ca2+
      concentration ([Ca2+]i) in HTC cells, either by activation of purinergic
      receptors with ATP or by inhibition of intracellular Ca2+ sequestration with
      thapsigargin, activated low-conductance (9-pS) K+ channels. Studies with excised
      membrane patches suggested that these channels were directly activated by Ca2+.
      Exposure of HTC cells to a permeant cAMP analog, 8-(4-chlorophenylthio)-cAMP,
      also activated 9-pS K+ channels but did not change [Ca2+]i. In excised membrane
      patches, cAMP-dependent protein kinase (the downstream effector of cAMP)
      activated K+ channels with conductance and selectivity identical to those of
      channels activated by Ca2+. In addition, cAMP-dependent protein kinase activated
      a distinct K+ channel type (5 pS). These data represent the differential
      regulation of low-conductance K+ channels by signaling pathways mediated by Ca2+
      and cAMP. Moreover, since low-conductance Ca(2+)-activated K+ channels have been
      identified in a variety of cell types, these findings suggest that differential
      regulation of K+ channels by hormones with distinct signaling pathways may
      provide a mechanism for hormonal control of solute transport and Ca(2+)-dependent
      cellular functions in the liver as well as other nonexcitable tissues.

PMID- 7624383
TI  - Genetic supercycles caused by cyclical selection.
AB  - Typical behavior of a two-locus genetic system experiencing cyclical selection,
      includes fixation (in one or both loci) or a stable polymorphic cycle with a
      period equal to that of environmental changes. By considering the time scale in
      terms of environmental periods, the last case could be trivially classified as a
      polymorphic stable point. Here we report on some results showing the complex
      limiting behavior of diploid population trajectories resulting from selection in
      a cyclically changing environment. We found that simple cyclical selection could
      produce genetic supercycles composed of many hundreds of environmental periods.

PMID- 7624384
TI  - Adherence to the first-AUG rule when a second AUG codon follows closely upon the
      first.

PMID- 7624385
TI  - Lithium and body weight gain.
AB  - Weight gain is an undesirable side-effect of long-term lithium administration
      which notably interferes with treatment compliance. The mechanisms of this weight
      gain remain unclear, making its management in patients difficult. In this paper,
      studies describing the features of this weight gain in patients and in rats
      treated with chronic lithium administration are reviewed. The effects of lithium
      on body weight differ between patients and rats in a number of ways, including
      the observation that excessive weight gain is observed in both male and female
      patients, but only in female rats. Nevertheless, an animal model of lithium
      induced weight gain may be able to provide useful insights into some of the
      specific mechanisms involved, particularly those related to interactions with
      gonadal steroid function. We discuss the effects of lithium on the endocrine
      system, neurotransmitters, metabolism, electrolyte regulation, and feeding
      behavior, which might underlie lithium's effects on body weight. Finally,
      suggestions for the management of weight gain in the clinical setting are
      presented. These include, in the long term, dietary control and physical activity
      and, in the short term, choosing among several drugs that have been tested either
      in patients or in animal models of obesity. If weight gain still cannot be
      controlled and treatment compliance is at risk, the mood stabilizers
      carbamazepine or valproic acid might be substituted for lithium treatment.

PMID- 7624386
TI  - Microstate segmentation of spontaneous multichannel EEG map series under diazepam
      and sulpiride.
AB  - Spontaneous multichannel brain electric field (EEG) map series of 20 seconds
      duration at 1, 15, 30, 45, and 60 minutes after the injection of a single dose of
      diazepam (13 ss) or sulpiride (6 ss) were segmented into microstates of quasi
      constant landscape but varying durations. Post-minus-preinjection difference
      values were computed for the six microstate variables: specific window size,
      duration, orientation, distance between windows, and location of center of
      gravity on the anterior-posterior and left-right axis. Differences between drugs
      were explored with ANOVAs. Microstate duration increased after sulpiride, and the
      location of the microstate center of gravity on the anterior-posterior axis moved
      to a more anterior position after diazepam. The results are in agreement with
      expectations based on measurements of patients' EEG microstates and with results
      using estimates of EEG model source locations in the frequency domain. Microstate
      segmentation appears to be a useful method for physiologically meaningful
      reduction of multichannel brain electric field data in psychopharmacology.

PMID- 7624387
TI  - Paroxetine as antidepressant in combined antidepressant-neuroleptic therapy in
      delusional depression: observation of clinical use.
AB  - The combination of antidepressive and antipsychotic (neuroleptic) medication is
      often used in the psychopharmacological treatment of delusional depression. In
      most studies of the treatment of delusional depression, tricyclic antidepressants
      have been used, and very little has been written about experience with SSRIs such
      as fluvoxamine, fluoxetine, or paroxetine. This paper therefore presents the
      preliminary findings of an open clinical study in which 14 delusional depressed
      inpatients, consecutively admitted to our Depression Unit, were given paroxetine
      combined with either zotepine or haloperidol. It was possible to observe a
      significantly impressive decline in the HAMD (24-item version) total score, of so
      called delusional items (HAMD subscore of items 2, 17, 18, 20, 23, 24) and of the
      subscore of remaining HAMD items over 21 treatment days. There were no unusual
      side-effects.

PMID- 7624388
TI  - Successful treatment with flupenthixol decanoate of a patient with both
      schizophrenia and alcoholism.
AB  - There is growing evidence that substance abuse is a major problem in patients
      with schizophrenia. With respect to alcohol, alledegly the most frequently abused
      drug among schizophrenics, clinical and epidemiological studies would suggest
      that the risk of alcoholism is approximately four times greater (Cuffel, 1992;
      Mueser et al., 1990; Soyka et al., 1993; Soyka, 1994). A variety of hypotheses
      have been proposed to explain this phenomenon, including the so-called "self
      medication hypothesis". Some authors feel that substance abuse in schizophrenics
      might be due to extrapyramidal and other side-effects caused by neuroleptic
      treatment or inadequate remission of psychotic symptoms. There remains, at
      present, an obvious lack of both psychosocial and psychopharmacological studies
      of treatment in "dual diagnosis" schizophrenics (Mueser et al., 1992). Changes in
      dopaminergic neurotransmission and dopamine-receptor dysfunction have been linked
      both to the development of psychotic symptoms and to alcoholism/substance abuse,
      and thus give rise to the question as to whether some dual diagnosis patients
      might benefit from neuroleptic treatment in both domains. A number of dopamine
      receptor subtypes in different regions of the brain seems to be involved in the
      development of schizophrenia and substance abuse. Modifications of D2-receptor
      subtype function have been implicated in psychotic symptoms, and changes in the
      D1- and D2-receptor function in substance abuse such as cocaine abuse and
      alcoholism (Spealman et al., 1990; 1991; 1992), especially in the mesolimbic
      dopaminergic reward system. Accordingly, the "ideal" neuroleptic drug for dual
      diagnosis schizophrenics should be effective in both receptor subtypes.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7624389
TI  - Absolutely therapy-resistant depression and mixed movement disorder in an unusual
      case of polycythemia vera.
AB  - This report presents a 64-year-old female patient with unusual psychiatric and
      neurological complications in polycythemia vera. Six years after onset of the
      hematologic disorder the patient succumbed to an absolutely therapy-resistant
      depression, from which she has been suffering for the past four years--intensive
      and broad--spectrum drug and electroconvulsive treatment has failed to ameliorate
      the condition. In addition, the patient has developed a mixed movement disorder
      with rhythmical movements, mainly affecting the trunk, akathisia,
      hyperventilation, and pleurothotonus ("Pisasyndrome"). The paper discusses a
      possible link between hypoxic cerebral damage, caused by hyperviscosity of the
      blood due to polycythemia vera, and the therapy resistance of the depression. The
      case confirms that organic factors may cause therapy resistance in depressive
      disorders.

PMID- 7624390
TI  - Cellular calcium transport in renal epithelia: measurement, mechanisms, and
      regulation.
AB  - The kidneys play a vital role in mineral homeostasis. In this review, the
      handling of calcium and the methods currently applied to measuring its
      intracellular concentration are discussed. The bulk of calcium absorption
      proceeds in proximal tubules, with smaller fractions recovered by thick ascending
      limbs, distal convoluted tubules, and connecting tubules. Hormonally regulated
      transcellular calcium absorption is essentially limited to distal convoluted and
      connecting tubules. At physiological concentrations, parathyroid hormone,
      calcitonin, and vitamin D increase net calcium absorption. Calcium absorption by
      polarized epithelial cells is a two-step process wherein calcium enters the cell
      across apical plasma membranes and exits across basolateral membranes. Recent
      electrophysiological and pharmacological experiments demonstrate that apical
      entry is mediated by calcium channels, which are modestly calcium selective,
      sensitive to dihydropyridine-type calcium channel blockers, and exhibit a wide
      range of single-channel conductances. Cellular calcium efflux is mediated by
      Ca(2+)-ATPase and by Na+/Ca2+ exchange. Ca(2+)-ATPase activity is highest in
      segments that exhibit significant rates of active calcium absorption. Multiple
      plasma membrane Ca(2+)-ATPase isoforms have been found in the kidney. Several
      renal Na+/Ca2+ exchange isoforms have been identified, and their role in
      effecting calcium efflux is under investigation.

PMID- 7624391
TI  - Pathophysiology of insulin resistance in human disease.
AB  - The ability of insulin to stimulate glucose uptake varies widely from person to
      person, and these differences, as well as how the individual attempts to
      compensate for them, are of fundamental importance in the development and
      clinical course of what are often designated as diseases of Western civilization.
      Evidence is presented that non-insulin-dependent diabetes mellitus (NIDDM)
      results from a failure on the part of pancreatic beta-cells to compensate
      adequately for the defect in insulin action in insulin-resistant individuals. In
      addition, a coherent formulation of the physiological changes that lead from the
      defect in cellular insulin action to the loss in glucose homeostasis is
      presented. However, the ability to maintain the degree of compensatory
      hyperinsulinemia necessary to prevent loss of glucose tolerance in insulin
      resistant individuals does not represent an unqualified homeostatic victory. In
      contrast, evidence is presented supporting the view that the combination of
      insulin resistance and compensatory hyperinsulinemia predisposes to the
      development of a cluster of abnormalities, including some degree of glucose
      intolerance, an increase in plasma triglyceride and a decrease in high-density
      lipoprotein cholesterol concentrations, high blood pressure, hyperuricemia,
      smaller denser low-density lipoprotein particles, and higher circulating levels
      of plaminogen activator inhibitor 1. The cluster of changes associated with
      insulin resistance has been said to comprise syndrome X, and all of the
      manifestations of syndrome X have been shown to increase risk of coronary heart
      disease. Thus it is concluded that insulin resistance and its associated
      abnormalities are of utmost importance in the pathogenesis of NIDDM,
      hypertension, and coronary heart disease.

PMID- 7624392
TI  - Regulation of differentiation of vascular smooth muscle cells.
AB  - The vascular smooth muscle cell (SMC) in mature animals is a highly specialized
      cell whose principal function is contraction. The fully differentiated or mature
      SMC proliferates at an extremely low rate and is a cell almost completely geared
      for contraction. It expresses a unique repertoire of contractile proteins, ion
      channels, and signaling molecules that are required for its contractile function
      and that when taken in aggregate clearly distinguish it from any other cell type.
      During vasculogenesis, however, the SMC's principal function is proliferation and
      production of matrix components of the blood vessel wall. Moreover, even in
      mature animals, the SMC retains remarkable plasticity, such that it can undergo
      relatively rapid and reversible changes in its phenotype in response to changes
      in local environmental cues normally required for maintenance of its
      differentiated state. A key to understanding SMC differentiation is to identify
      the key environmental signals and factors that induce or maintain the
      differentiated state of the SMC and to determine the molecular mechanisms that
      control the coordinate expression of genes encoding for proteins that are
      necessary for the contractile function of the SMC. The purpose of this review is
      to summarize our current knowledge of the regulation of SMC differentiation, with
      a particular emphasis on consideration of how this process is controlled during
      normal vascular development and how these control processes might be altered in
      vascular diseases such as atherosclerosis, which are characterized by marked
      alterations in the differentiated state of the SMC.

PMID- 7624394
TI  - Modulation of epithelial permeability by extracellular macromolecules.
AB  - Epithelia are sheets of cells joined together by tight junctions. This geometry
      allows an epithelium to act as a barrier, i.e., restrict the movement of
      substances between two compartments that it separates (typically 1 compartment is
      the blood) and also to actively and selectively transport substances between the
      two compartments. It has been known for a number of years that both the barrier
      and transport functions of epithelia can be regulated by hormones and
      neurotransmitters, and this regulation is a central component of plasma
      electrolyte and nonelectrolyte homeostasis. Less appreciated is that these
      epithelial functions can be modified by macromolecules other than
      neurotransmitters and hormones. These macromolecules have been divided into the
      following categories: proteases, cytokines, cellular constituents, nonbacterial
      xenobiotics, and bacterial xenobiotics. Such macromolecules can alter epithelial
      transport and barrier function by a number of different mechanisms. These include
      proteolysis of epithelial ion channels and tight junctional complexes, conversion
      of an ion pump into a nonselective cation channel, increase in epithelial
      membrane permeability resulting in cell swelling and lysis, and up- or
      downregulation of cellular second messenger systems that can alter ion transport
      capabilities or prove cytotoxic to the cells. Finally, these modifications can be
      either transient or chronic in nature and in many circumstances result in a
      perturbation of the electrolyte and nonelectrolyte status of the host organism.

PMID- 7624395
TI  - The asialoglycoprotein receptor: relationships between structure, function, and
      expression.
AB  - Transport of macromolecules into the cell by receptor-mediated endocytosis
      follows a complex series of intracellular transfers, passing through distinct
      environments. The asialoglycoprotein receptor is a prototype of the class of
      receptors that constitutively enters cells via coated pits and delivers ligand to
      these intracellular compartments. In addition to being a model of receptor
      mediated endocytosis, the presence of the receptor on hepatocytes provides a
      membrane-bound active site for cell-to-cell interactions, has made possible the
      selective targeting of chemotherapeutic agents and foreign genes, and has also
      been implicated as a site mediating hepatitis B virus uptake. Regulated
      expression of receptor subunits and their intracellular trafficking during
      biosynthesis and endocytosis has provided insights into the relationship of
      receptor structure to its overall function. As a marker of hepatocellular
      differentiation, its study has uncovered a unique response to intracellular
      guanosine 3',5'-cyclic monophosphate and translational regulation of the
      receptor. In this review, an overview of these diverse findings is provided in an
      attempt to relate the various aspects of structure and function as they impact on
      receptor expression.

PMID- 7624396
TI  - Local control of veins: biomechanical, metabolic, and humoral aspects.
AB  - The incidence of vein diseases (varicosity, thrombophlebitis, phlebosclerosis,
      orthostatic intolerance) is extremely high. In several countries it may exceed
      that of the arterial pathology by an order of magnitude. In the last decades,
      this recognition and the rapid accumulation of experimental data have resulted in
      a progressive reevaluation of the physiological significance of the venous
      system, which had been rather neglected earlier by scientists. The major aim of
      this review is to provide a critical survey of recent selected literature related
      to different physiological functions of the venous system as well as to
      biomechanical, metabolic, and humoral (ionic, hormonal) aspects of the local
      venous control. Local neural control mechanisms, including effects of
      catecholamines and other transmitters, are regarded to be beyond the scope of
      this work. At present, the synthesis of information available in the literature
      meets certain difficulties, because occasionally poorly defined methodological
      techniques and physiological parameters have been applied. On the other hand, a
      significant part of works dealing with venous physiology is excellent and
      inspirational. We have good reason to believe that the fast accumulation of
      reliable scientific data on this very important field will soon reach a new
      critical level, then an even more effective integration of knowledge will be
      possible.

PMID- 7624397
TI  - Topical application of epidermal growth factor onto partial-thickness wounds in
      human volunteers does not enhance reepithelialization.
AB  - Recent reports have suggested that human epidermal growth factor will accelerate
      the healing of corneal wounds and donor sites of burned patients undergoing split
      thickness skin grafts. In one report using human epidermal growth factor in a
      silver sulfadiazine cream, these data were gathered from patients of various ages
      who had various depths of donor sites and degrees of burn. Therefore, despite the
      fact that these data were prospective, randomized, and double-blinded, we
      questioned the validity of the study. To test the hypothesis that topical
      application of human epidermal growth factor will enhance the healing of partial
      thickness wounds, we utilized healthy volunteers (n = 17) and created bilateral
      split-thickness skin wounds (4 cm2) of the same depth (0.014 in) on each flank
      and then studied time until total epithelialization occurred. One side was
      treated with silver sulfadiazine as a control and the opposite side with silver
      sulfadiazine and human epidermal growth factor. There was no significant
      difference in the healing times between the human epidermal growth factor-treated
      sites and the silver sulfadiazine cream controls.

PMID- 7624399
TI  - Cumulative operative procedures in patients aged 14 years and older with
      unilateral or bilateral cleft lip and palate.
AB  - Sixty-seven consecutive patients over the age of 14 with either unilateral (n =
      38) cleft lip and palate or bilateral (n = 29) cleft lip and palate seen over a
      15-month period at the University of Michigan Craniofacial Program were reviewed
      to determine the total number of surgical procedures performed over the course of
      treatment. The demographics of the two groups differed: There were 25 males and
      13 females who were a mean age of 17 years and 9 months with unilateral cleft lip
      and palate and 23 males and 6 females who were a mean age of 18 years and 5
      months with bilateral cleft lip and palate. Lip and palate repairs were carried
      out on all patients. Lip adhesions were performed in 29 and 62 percent;
      pharyngoplasties (either pharyngeal flap or modified Ortichochea) in 39 and 38
      percent; alveolar bone grafts in 82 and 79 percent; Abbe flaps in 0 and 10
      percent; and orthognathic surgery was done in 10.5 and 13.8 percent and
      recommended and/or done in 26 and 24 percent of patients with unilateral cleft
      lip and palate and bilateral cleft lip and palate, respectively. Lip revisions
      averaged 1.13 and 2.17 per patient and secondary nasal surgeries averaged 1.13
      and 1.18 per patient in the unilateral cleft lip and palate and bilateral cleft
      lip and palate, respectively. All totaled, the average number of operations was
      6.12 per patient (range 3 to 12) in the unilateral cleft lip and palate and 8.04
      per patient (range 5 to 15) in the bilateral cleft lip and palate.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7624398
TI  - Cleft-orthognathic surgery: complications and long-term results.
AB  - We reviewed the complications and long-term results of a consecutive series of
      adolescents (67 males, 49 females; age range 15 to 25 years; mean 18 years) born
      with a cleft who underwent primary repair in childhood and later developed a jaw
      deformity and malocclusion that required orthognathic surgery. Between 1986 and
      1992, 116 adolescents with either unilateral cleft lip and palate (n = 66),
      bilateral cleft lip and palate (n = 33), or isolated cleft palate (n = 17)
      underwent an orthognathic procedure that included a Le Fort I osteotomy; 32 also
      underwent simultaneous sagittal split osteotomies of the mandible; and 87
      underwent osteoplastic genioplasty. Clinical follow-up ranged from 1 to 7 years
      (mean 40 months) at the close of the study. The preoperative clinical examination
      varied according to cleft type and individual variation, but all patients had
      maxillary hypoplasia. Additional cleft-related deformities included residual
      oronasal fistula and bony defects, clefted alveolar ridges that retained dental
      gaps, and mobile premaxilla that lacked union to the lateral segments. Overall,
      89 percent of residual fistulas underwent successful closure as part of the
      orthognathic procedure. Surgical cleft dental gap closure was achieved and
      maintained to the extent planned at 92 percent of the cleft sites. A fixed
      (prosthetic) bridge was used successfully for dental rehabilitation to close the
      gap in all other patients at each cleft site (n = 9). All patients with alveolar
      clefts (n = 99) maintained keratinized mucosa along the labial surface of the
      cleft-adjacent teeth (n = 264 teeth). Complications were few and generally not
      serious. There was no segmental bone loss of teeth because of aseptic necrosis or
      infection. Only 5 percent of cleft adjacent teeth underwent a degree of gingival
      recession and root exposure as a result of the maxillary osteotomy procedure; all
      were retained long term. The long-term maintenance of overjet and overbite
      measured directly from the late (> 1 year) postoperative lateral cephalometric
      radiograph indicated that 97 percent of patients maintained a positive overjet
      and 89 percent maintained a positive overbite; 5 percent shifted to a neutral
      overbite. The methods used to manage jaw deformity, malocclusion, residual
      oronasal fistula, and bony defects in adolescents born with a cleft are safe and
      reliable and offer the patient an enhanced quality of life. They also provide a
      stable foundation in which final soft-tissue lip and nose revisions may be
      carried out.

PMID- 7624400
TI  - Twenty-year experience with early surgery for craniosynostosis: I. Isolated
      craniofacial synostosis--results and unsolved problems.
AB  - Early surgery for isolated craniosynostosis is designed to improve morphology, to
      prevent functional disturbances, and equally important, to enhance the
      psychosocial development of the child. As the first of a two-part series, 104
      patients with isolated craniofacial synostosis were retrospectively analyzed.
      Diagnoses included bilateral coronal (10), unilateral coronal (57), metopic (29),
      and sagittal synostosis (8). All patients underwent primary fronto-orbital
      advancement-calvarial vault remodeling procedures at less than 18 months of age
      (mean 8.1 months). Thirteen percent of patients (14) required a secondary cranial
      vault operation (mean age 22.6 months) to address residual deficits in
      craniofacial form. Perioperative complications were minimal (5.0 percent), and
      there was no mortality. Average length of postoperative follow-up was 46.0
      months. By the classification of Whitaker et al., which assesses surgical
      results, 87.5 percent of patients were considered to have at least satisfactory
      craniofacial form (category I-II) at latest evaluation. Overall rates of
      hydrocephalus, shunt placement, and seizures (3.8, 1.0, and 2.9 percent,
      respectively) were low. Among the isolated craniosynostoses, unilateral coronal
      synostosis/plagiocephaly poses the most complex problems, including vertical
      orbital dystopia, nasal tip deviation, and residual craniofacial asymmetry; there
      is also a wide spectrum of findings and growth patterns in this subgroup.

PMID- 7624401
TI  - Twenty-year experience with early surgery for craniosynostosis: II. The
      craniofacial synostosis syndromes and pansynostosis--results and unsolved
      problems.
AB  - As the second of a two-part series, 76 patients with pansynostosis and
      craniofacial synostosis syndromes were retrospectively analyzed. Diagnoses
      included pansynostosis (7), craniofrontonasal dysplasia (8), and Apert (24),
      Crouzon (15), and Pfeiffer (15) syndromes. All patients underwent primary fronto
      orbital advancement-calvarial vault remodeling procedures at less than 18 months
      of age (mean 6.1 months). Twenty-eight patients (36.8 percent) required a
      secondary cranial vault operation (mean age 28.4 months). Additionally, a major
      tertiary procedure was necessary in 5 patients to deal with persistent
      unacceptable craniofacial form. To address the associated finding of midface
      hypoplasia, 64.8 percent (n = 35) of patients underwent Le Fort III midface
      advancement or had that procedure recommended for them. The remainder were
      awaiting appropriate age for this reconstruction. The more extensive pathologic
      involvement of the pansynostosis and craniofacial syndrome group is illustrated.
      As compared with the isolated craniofacial synostosis group previously reported,
      the incidence of major secondary procedures (36.8 versus 13.5 percent),
      perioperative complications (11.3 versus 5.0 percent), follow-up complications
      (44.7 versus 7.7 percent), hydrocephalus (42.1 versus 3.9 percent), shunt
      placement (22.4 versus 1.0 percent), and seizures (11.8 versus 2.9 percent) was
      significantly increased. Complex problems including those of increased
      intracranial pressure, airway obstruction, and recurrent turricephaly or cranial
      vault maldevelopment are repeatedly encountered. In addition, that early fronto
      orbital advancement-cranial vault remodeling failed to promote midface
      development and hypoplasia of this region is almost a consistent finding in the
      craniofacial syndromic group. The average length of postoperative follow-up was 6
      years. According to the classification of Whitaker et al., which assesses
      surgical results, 73.7 percent of patients were considered to have at least
      satisfactory craniofacial form (category I-II) at latest evaluation. An
      algorithmic approach to the treatment of all patients with craniosynostosis is
      presented utilizing early surgical intervention as the key element.

PMID- 7624402
TI  - Metopic and sagittal synostosis: intracranial volume measurements prior to and
      after cranio-orbital reshaping in childhood.
AB  - This study applied a proven method for obtaining intracranial volume measurements
      using CT scans to (1) measure the intracranial volume of a consecutive series of
      children with either metopic or sagittal synostosis prior to any craniofacial
      procedure, (2) perform a standard cranio-orbital operation in each child, follow
      them longitudinally, and remeasure their intracranial volume 1 year later, and
      (3) compare their intracranial volumes with those of an age- and gender-matched
      cohort and review their cranial growth velocity. The study included 18 children
      who presented sequentially with untreated isolated nonsyndromic sagittal (n = 8)
      and metopic (n = 10) synostosis between 1987 and 1990 and who subsequently
      underwent cranio-orbital reconstruction by the senior author (Posnick) in
      conjunction with a pediatric neurosurgeon. The primary method of osteotomy and
      bone-graft fixation varied (i.e., wires, miniplates and microplates and screws).
      The series included 5 females and 13 males with an average age at the time of
      operation of 27 months (range 6 to 87 months). The postoperative clinical follow
      up ranged from 13 to 47 months at the close of the study. Comparison of our
      patients' preoperative intracranial volumes with age- and gender-matched volumes
      available through Lichtenberg showed that 16 of 18 (89 percent) had volumes at or
      greater than the mean, with 44 percent (7 of 16) exceeding 2 standard deviations
      above the mean. When comparing our patients' late postoperative volumes with the
      Lichtenberg normative measurements, 94 percent achieved values at or greater than
      the mean. All patients achieved increased intracranial volume in association with
      the surgery performed and the time that lapsed between scan intervals. The
      majority of our patients (16 of 18) followed an intracranial volume growth curve
      that closely approximated the norm but with a starting point determined by the
      preoperative value. Two of 18 followed a growth curve that exceeded the rate of
      expansion expected for normal children. Our findings suggest that premature
      closure of either the sagittal or metopic suture does not result in diminished
      intracranial volume prior to or after the cranio-orbital procedures carried out
      in childhood. For the majority of the children in our study, both the
      preoperative intracranial volume and the rate of cranial expansion approximated
      or surpassed that of children without synostosis. The surgical techniques of
      skull and upper orbital reshaping with varied forms of osteotomy and graft
      fixation did not result in a global form of growth restriction. These findings
      are contrary to standard thinking about the biologic effects of craniosynostosis
      and raise new questions about our rationale for treatment.

PMID- 7624403
TI  - A comparison of resorbable and metallic fixation in healing of calvarial bone
      grafts.
AB  - The effects of a resorbable fixation plate composed of a polylactic acid
      polyglycolic acid copolymer were compared with those of a metallic fixation plate
      of similar dimensions in an animal calvarial bone-graft healing model. Bilateral
      parietal bone grafts in 20 mature rabbits were fixed into position with a
      titanium mesh plate on one side and a polymer mesh plate on the other side. After
      2, 6, 9, and 12 months, cross-sectional histology was used to compare osteotomy
      line healing, tissue response to the fixation material, and the amount of
      resorbable plate degradation. After 2 months, no changes in the dimensions of the
      resorbable plate were observed. The bone grafts fixed by both metal and polymer
      plates exhibited incomplete healing along the osteotomy lines. After 6 months,
      there was a 66 percent reduction in the dimensions of the resorbable plate and
      vertical shortening of screw length. Complete healing was seen along all
      osteotomy lines of both bone grafts. After 9 months, less than 1 percent of the
      resorbable mesh plate remained as a small film underneath a collagenous capsule.
      No polymer was seen within the confines of the screw holes. After 1 year, no
      evidence of polymer was seen either on the external cranial surface or within any
      of the screw holes. Bony union was observed across all osteotomy sites. The screw
      hole outlines persisted. The resorbable plate demonstrated fixation stability
      similar to that of metal with comparable osteotomy line healing. No adverse local
      inflammatory reactions were seen as the polymer composite progressed to complete
      degradation by 1 year.

PMID- 7624404
TI  - Endoscopically assisted biplanar forehead lift.
AB  - The standard subgaleal coronal incision used for brow lifting is limited to
      patients with low foreheads. The subcutaneous hairline brow lift used for
      patients with high foreheads has a high rate of vascular complications. However,
      the main advantage of the subcutaneous approach is preservation of sensation
      posterior to the incision line. The subperiosteal approach, on the other hand,
      allows a better periorbital remodeling. I have combined the subperiosteal and the
      subcutaneous approach to take advantage of and minimize the disadvantages of each
      individual approach. The advent of the endoscopic technique has allowed more
      accurate and controlled periorbital dissection and brow depressor muscle
      modification. The operation is indicated in every patient in whom the anterior
      hairline incision is indicated. It is a good method for decreasing the height of
      the forehead. The dissection is done initially in the subcutaneous plane, and
      about halfway on the forehead slit incisions through the galea-periosteal layer
      and through the temporoparietal fascia are made to continue the dissection in the
      deep plane. The periosteal dissection and release at the arcus marginalis is done
      under endoscopic control. Likewise, the brow depressor muscle modification is
      done under endoscopic magnification. Deep anchoring sutures fix the brow in the
      elevated position. Trimming and closure of the cutaneous layer are done with
      minimal tension. The biplanar subperiosteal-subcutaneous forehead lift has been
      used in 24 patients with very satisfactory results. Complications have been of a
      minor nature. Patients have maintained sensation posterior to the hairline
      incision. The height of the forehead has been decreased in every case. Frontalis
      muscle function has been preserved.

PMID- 7624393
TI  - Flow-mediated endothelial mechanotransduction.
AB  - Mechanical forces associated with blood flow play important roles in the acute
      control of vascular tone, the regulation of arterial structure and remodeling,
      and the localization of atherosclerotic lesions. Major regulation of the blood
      vessel responses occurs by the action of hemodynamic shear stresses on the
      endothelium. The transmission of hemodynamic forces throughout the endothelium
      and the mechanotransduction mechanisms that lead to biophysical, biochemical, and
      gene regulatory responses of endothelial cells to hemodynamic shear stresses are
      reviewed.

PMID- 7624405
TI  - Lateral thigh free flap in head and neck reconstruction.
AB  - To understand the role of the lateral thigh flap in head and neck reconstruction,
      we performed injection studies and anatomic dissections in 2 fresh and 61
      preserved cadaver extremities followed by 10 clinical cases involving defects
      after tumor ablation. The flap, based on the third perforator of the profunda
      femoris artery, is designed on the posterolateral aspect of the distal thigh. The
      pedicle courses through the biceps short head, allowing optional transfer of this
      muscle. Defects of the oral cavity, pharynx, cervical esophagus, and external
      skin were successfully restored. One flap was unsuccessful because of
      intraoperative injury to the vascular pedicle. Compared with the radial forearm
      flap, the lateral thigh flap provides more tissue and the donor scar is more
      easily hidden, but the vascular pedicle is shorter, of smaller caliber, and more
      variable. The lateral thigh flap provides thin, pliable, and reliable tissue for
      a variety of needs in properly selected patients.

PMID- 7624406
TI  - Prefabricated vertical myocutaneous flap of the nose in facially burned patients.
AB  - In facially burned patients, a simple and effective technique is described for
      reconstruction of deformities of the lower third of the nose. The first stage
      consists of replacing the dorsal scarred skin with a skin graft from the buttocks
      or other area. The second stage is a vertical columella-based prefabricated flap
      that is outlined beginning near the tip of the nose and extending superiorly to
      the glabellar region. This flap is raised with the underlying muscle as a
      composite tissue, transposed to the defect, and sutured to the vestibular mucous
      membrane or the integument of the remaining portions of the nose at the alar rim.
      This very well vascularized vertical prefabricated myocutaneous flap can cover a
      cartilage graft taken from the ear to reconstruct an alar rim. The donor site is
      closed by undermining the nasal skin laterally on each side and suturing the
      edges at the dorsum to leave an acceptable midline scar. In patients for whom a
      nasolabial flap or other technique is not suitable or is impossible, this new and
      simple technique may be used successfully.

PMID- 7624407
TI  - Use of the orbicularis muscle flap for complex lower lid problems: a 6-year
      analysis.
AB  - There are several groups of patients seeking lower lid blepharoplasty who present
      with the potential for unsatisfactory postoperative results, such as those
      presenting with atonic eyelids, patients with severe blepharochalasis alone or
      with large fat bags, patients with festoons, those with abnormal anatomy, and
      patients with deformity due to prior surgery. The orbicularis muscle flap
      technique provides good results in patients with potentially problematic lower
      eyelids. Of 600 blepharoplasties, 8.5 percent underwent the orbicularis muscle
      flap procedure. Follow-up time was 1.3 years, and average patient age was 54
      years. Details of this technique are described together with results, including
      illustrative photographs. Of 51 patients, 49 had excellent or acceptable results
      and 2 had unacceptable results, 1 of whom required a small correction. This
      method produces a "minilift" of the lower eyelid and upper cheek skin that cannot
      be achieved with the standard lower eyelid blepharoplasty as described to date.

PMID- 7624408
TI  - Arcus marginalis release and orbital fat preservation in midface rejuvenation.
AB  - With aging, the periorbital area reveals progressive exposure of underlying
      skeletal anatomy as compared with the lower areas of the face, whose thicker soft
      tissues continue to cover underlying bony landmarks. With recent techniques in
      cheek fat repositioning and orbicularis muscle repositioning, rejuvenation
      results of the midface have been markedly improved. Conventional lower
      blepharoplasty techniques that remove lower eyelid fat can create a concave
      contour deformity of the lower eyelids that causes the "operated" appearance.
      This paper describes a new technique to preserve the lower eyelid fat and to
      advance it beyond the infraorbital rim. An arcus marginalis release is
      accomplished, and the subseptal fat is advanced and sutured beyond the entire
      infraorbital rim and under the repositioned orbicularis muscle. By camouflaging
      the lower orbital rim anatomy, rejuvenation of the midface is more complete. A
      total of 152 cases have been done over a 3-year period with impressive results
      and minimal complications. This procedure is done in all composite rhytidectomies
      and in isolated blepharoplasty patients without advanced facial aging. It is
      particularly indicated in secondary procedures correcting overresection of
      orbital fat or deformities resulting from malar augmentation.

PMID- 7624409
TI  - Conservative treatment of breast cancers by mammaplasty and irradiation: a new
      approach to lower quadrant tumors.
AB  - Conservative treatment of breast cancers confined to the lower quadrants often
      leaves a residual deformity. In order to prevent these poor cosmetic results, 20
      patients with lower quadrant cancers have been treated since 1986 at the Institut
      Curie by wide lumpectomy combined with immediate remodeling of the gland by
      nipple-bearing superior pedicle mammaplasty and preoperative (9 cases) or
      postoperative (11 cases) irradiation. The contralateral breast was always
      rendered symmetrical at the same time. The mean weight of resection was 248 gm,
      and the resection margins were always free of tumor. The treatment protocols were
      not modified by the addition of mammaplasty to lumpectomy, and this combination
      did not induce any significant complications. The mean follow-up was 4.5 years
      (range 1 to 7.5 years). There was one case of local recurrence; there were four
      cases of metastases. In this series, the oncologic results were identical to
      those of conventional treatment by lumpectomy and irradiation. The cosmetic
      result was good or very good in 75 percent of patients and 91 percent of patients
      in the group in which mammaplasty was performed prior to irradiation. Treatment
      of breast cancers by superior pedicle reduction mammaplasty and irradiation is
      indicated in tumors located in the lower quadrants, whose size in relation to the
      breast volume is such that conventional conservative treatment by lumpectomy and
      irradiation would achieve a poor cosmetic result.

PMID- 7624411
TI  - Breast augmentation with autologous tissue: an alternative to implants.
AB  - The demand for alternative methods in lieu of silicone implants has been
      increasing for quite some time. Whereas saline implants have been in use in the
      United States for a number of years, I describe in detail a new variation of the
      established latissimus dorsi musculocutaneous flap and its application in breast
      augmentation. A small strip of the latissimus dorsi muscle is utilized as a
      pedicled deepithelialized dermis and fat flap just sufficient to support the
      thoracodorsal vessels, leaving the major part of the muscle functionally intact.
      In 13 patients 20 flaps were transposed by this method. The time required for the
      operation was reduced to less than 1 hour for each breast. Results suggest that
      the operation can be a true alternative to implants.

PMID- 7624410
TI  - Repeated exposure to silicone gel can induce delayed hypersensitivity.
AB  - The possible immunologic reactivity of silicone gel remains speculative and
      controversial. In this laboratory, a quantitative lymphocyte localization assay
      has been developed and well studied using pure lymphocytes collected by the
      technique of lymph vessel cannulation in sheep. The kinetics of antigen-specific
      immune responses (e.g., tuberculin reaction) in this model are well described and
      accepted. Using the known parameters regarding the response to purified protein
      derivative and the classic adjuvant Freund's Complete Adjuvant, this study was
      designed to identify the possible antigen-specific immunologic response, in the
      form of delayed-type hypersensitivity, after repeated exposure to silicone gel.
      Pure lymphocytes were collected by cannulating the efferent vessel of a
      subcutaneous lymph node in four groups of primed sheep which, 30 days previously,
      had received intradermal injections of 0.9% saline (negative controls; n = 6),
      Freund's Complete Adjuvant only (positive controls; n = 6), silicone gel (n = 7),
      or Freund's Complete Adjuvant homogenized with silicone gel (n = 7) in an attempt
      to induce sensitization. Multiple (1040) intradermal skin tests were performed
      using silicone gel, purified protein derivative, and 0.9% saline. After the skin
      lesions had developed for 48 hours, 5 x 10(8) lymphocytes were labeled in vitro
      with indium-111, returned intravenously, and allowed to circulate for 3 hours.
      Sheep were euthanized, the skin lesions were removed, and the radioactivity was
      counted in a gamma spectrometer. The radioactivity in each skin lesion is
      considered a measure of lymphocyte accumulation. The occurrence of augmented
      accumulation after reexposure to an antigen is a hallmark of delayed-type
      hypersensitivity. The purified protein derivative and saline lesions functioned
      as positive and negative controls, with counts per minute (cpm +/- standard
      error) of 2404 +/- 478 (Freund's Complete Adjuvant group) and 149 +/- 21 (saline
      group), respectively. Significantly greater (p = 0.0021) radioactivity was found
      in the silicone gel sites (310 +/- 35) in the silicone gel-primed group and the
      Freund's Complete Adjuvant plus silicone gel group (453 +/- 44; p = 0.0004) than
      in normal skin in each group. These data suggest that it may be possible to
      induce an antigen-specific lymphocyte-mediated response to silicone gel.

PMID- 7624412
TI  - Chest-wall contouring in female-to-male transsexuals: basic considerations and
      review of the literature.
AB  - In order to obtain satisfactory results in chest-wall contouring as part of
      gender-confirming surgery in female-to-male transsexuals, the surgeon should be
      aware of the differences between the female and male mammary anatomy and should
      take notice of the possible techniques to overcome these differences. So far, not
      much attention has been given to either. The basic considerations involving
      reduction of breast tissue and skin excess, the proper reduction and positioning
      of the nipple-areola complex, the obliteration of the inframammary crease, and,
      where possible, the obviation of chest-wall scars are presented and discussed.

PMID- 7624413
TI  - Prefabricated recipient vascular pedicle for free composite-tissue transfer in
      the chronic stage of severe leg trauma.
AB  - Reconstruction of a severely traumatized lower limb with a composite defect, in
      the chronic stage, is theoretically possible by free composite-tissue transfer of
      anatomic dimensions. However, in practice, because of extensive fibrosis around
      the bony defect and the extension of perivascular fibrosis for several
      centimeters beyond the visible limits of trauma, a healthy recipient pedicle is
      not available in the vicinity of the defect. Since most composite flaps have a
      short pedicle, vein grafts have to be used for both the artery and the vein. The
      procedure becomes very demanding of both time and skill and is prone to
      complications. Prefabrication of a recipient vascular pedicle is done by creating
      a popliteosaphenous shunt by means of a vein graft 1 week before definitive flap
      transfer. The procedure becomes two-staged but safe. The operating time is short
      in each sitting. The prefabricated recipient pedicle can be made to reach almost
      next to the bony defect; thus there is freedom of flap selection. The anastomosis
      is technically simple. I have used the prefabricated recipient vascular pedicle
      method to salvage 11 cases of extensive leg trauma in the chronic stage by
      transfer of large composite-tissue flaps with no failures.

PMID- 7624415
TI  - Association of Wartenberg's syndrome and De Quervain's disease: a series of 26
      cases.
AB  - We report on a series of 25 patients (26 cases) presenting an association of
      Wartenberg's radial neuritis and De Quervain's tenosynovitis. In all patients the
      diagnosis was made on clinical grounds. In group 1, conservative treatment of
      Wartenberg's syndrome was used in 16 patients (associated with surgical release
      of the first extensor compartment in 5 patients). Of the 14 patients available
      for follow-up at an average of 15 months, 9 (64 percent) were excellent and good
      results. In group 2 (11 patients, with 1 failure of conservative treatment),
      surgical treatment addressed both conditions. Neurolysis has to be performed at
      the classic proximal site of entrapment (constant excellent and good results),
      for the 2 cases of neurolysis at the styloid level gave fair results. It is
      particularly important to identify an associated Wartenberg's syndrome before
      performing a release of the first dorsal compartment to avoid incomplete relief
      or even aggravation of neuritis, exposing the surgeon to litigation.

PMID- 7624414
TI  - The posterolateral malleolar flap of the ankle: a distally based sural
      neurocutaneous flap--report of 14 cases.
AB  - The posterolateral malleolar flap is a fasciocutaneous flap designed on the
      principles of distally based neurocutaneous flaps. It is based distally at the
      level of the lateral retromalleolar gutter. Elevation of the flap involves the
      proximal sectioning of the sural nerve, which contributes to its vascularization
      by reversed flow. This is a very reliable flap, even in patients with distal
      arterial insufficiency. For this reason, it has emerged, in our experience, as
      the method of choice in the treatment of heel necrosis. Fourteen cases are
      reported, of which six were elderly patients.

PMID- 7624416
TI  - The effect of cold ischemia on the patency of microvascular repair following
      arterial avulsion injury.
AB  - Avulsion injuries have a poor prognosis for survival in clinical replantation
      surgery. Arterial thrombosis is the most significant factor contributing to
      avulsion replant failure, and severe arterial damage has been observed with this
      injury. However, patency rates of experimentally avulsed arteries repaired
      immediately are much higher than in the clinical situation. This paper evaluates
      the effect of an added component--ischemia--on the patency of experimentally
      avulsed arteries. All avulsions seen clinically are subject to some degree of
      ischemia prior to replantation. Ninety rabbits had both femoral arteries avulsed
      under general anesthesia. A 6.5-cm graft was harvested from the left distal
      femoral artery. In 20 rabbits (group 1: 0 hours of ischemia) the graft was
      immediately inserted into the defect in the right femoral artery. Sixty rabbits
      (20 grafts per group) had their grafts stored at 4 degrees C for either 10 hours
      (group 2), 18 hours (group 3), or 24 hours (group 4) and reinserted into the
      right femoral artery in a second operation. Patency was assessed 3 weeks after
      reinsertion. Groups 1 and 2 maintained high patency rates (85 percent); however,
      group 3 (70 percent) and group 4 (45 percent) had lower patency rates than group
      1, with a significant difference between groups 1 and 4 (p < 0.01). In a fifth
      group (10 grafts), avulsed 24-hour ischemic grafts were hydrodilated prior to
      reinsertion. The patency rate of this group increased significantly (90 percent)
      compared with group 4 (p < 0.005). CONCLUSION: These experiments suggest that a
      combination of avulsion injury and ischemia time is responsible for the poor
      clinical results of avulsion replantations.

PMID- 7624417
TI  - Evaluation of a pressure sore model using monoplegic pigs.
AB  - This study evaluated a newly developed swine monoplegic pressure sore model by
      testing the uniformity of the initial wound size. The natural healing also was
      evaluated. Nine minipigs were used. The hindlimb was denervated by transecting
      the unilateral nerve roots L1 through S2. At 5 to 14 days, 800 mmHg of pressure
      was applied to the denervated skin over the trochanteric area with a 3-cm
      diameter disk compressing the skin and subcutaneous tissue against the underlying
      bone for 48 hours. The wound was then debrided of devascularized tissue. Wound
      surface areas were calculated from photographs. Wound volumes were obtained by
      measuring the volume of saline needed to fill the wound defect. Full-thickness
      sores of uniform size developed in all pigs without mortality or complications.
      Wound surface area and volume increased initially, peaked, and then decreased in
      an exponential fashion. This model provides a new tool for direct comparison of
      pressure sore treatment modalities for short- and long-term studies.

PMID- 7624419
TI  - Escaping accountability: a feature of our times.

PMID- 7624418
TI  - In vivo 31P-NMR studies of age and energy metabolism in an animal flap model.
AB  - Changes in phosphate energy metabolism with time in a rat flap model were
      followed noninvasively with in vivo 31P-NMR. The influence of age on high-energy
      phosphate metabolites in perfused and ischemic ends of 3 x 10 cm dorsal flaps was
      noted from 30 minutes to 7 days after closure in 6-, 12-, and 24-month-old (n =
      4, 7, and 8, respectively) male Fischer 344 rats. Phosphocreatine to inorganic
      phosphate ratios showed younger animals exhibiting significant returns to
      preinjury energy status in 2- and 3-mm ischemic layers. This behavior, 24 to 72
      hours after closure, coincides with neovascularization of the flap tissue. By
      contrast, 12- and 24-month-old animals experienced statistically significantly
      lesser high-energy rebound, developing greater necrosis in the ischemic regions.
      Early intracellular pH lowering, indicative of lactate production, was somewhat
      greater in the flaps of younger animals. The in vivo 31P-NMR methods thus provide
      metabolic insights into flap behavior correlating with physiologic influences of
      aging.

PMID- 7624420
TI  - Aneurysmal bone cyst of the orbit associated with fibrous dysplasia.
AB  - Aneurysmal bone cyst is a rare but recognized osseous lesion of the orbit. We
      report the presentation, treatment, and postoperative course of an orbital
      aneurysmal bone cyst in a patient with McCune-Albright syndrome. To our
      knowledge, this report represents the first description of aneurysmal bone cyst
      of the orbit in a patient with fibrous dysplasia. Although visual loss in
      patients with fibrous dysplasia is most commonly due to narrowing of the optic
      canal, aneurysmal bone cyst should be considered in a patient with fibrous
      dysplasia who presents with decreasing vision in the face of a rapidly expanding
      orbital mass. The treatment in this case was drainage and debridement with prompt
      resolution. Although not necessary in this case, an alternative treatment
      includes packing with bone chips. Radiation is usually avoided because of the
      risk of iatrogenically induced sarcoma.

PMID- 7624421
TI  - Videoendoscopic subcutaneous techniques for aesthetic and reconstructive plastic
      surgery.

PMID- 7624422
TI  - Early free-flap debulking: avoiding the second donor site.
AB  - The advantages of this technique in large, shallow defects are: 1. The flap can
      be monitored clinically during the critical postoperative period. 2. The
      aesthetic result is much better than that of the bulky myocutaneous flap. 3. No
      second donor site for the split-thickness skin graft is required.

PMID- 7624423
TI  - Retrieval of the retracted flexor tendon.
AB  - A simple and easy technique to retrieve the retracted flexor tendon across the
      sheath is described. Skill and atraumatic handling of the tendon are emphasized
      by employing the same suture to accomplish tendon delivery and repair.

PMID- 7624424
TI  - A new operative method for treating severe cryptotia.
AB  - Results following surgical treatment for cryptotia are as yet far from fully
      satisfactory in cases in which deformity of the upper auricular portion is severe
      and particularly when there is contraction of the helical skin and auricular
      cartilage. Therefore, improvements in operative procedures have been considered
      necessary. We have developed a new method for treating cryptotia using a rhomboid
      flap in the superior and anterior auricular regions to correct the contraction of
      skin in the helix in cases in which the deformity of the upper auricular portion
      is large and shortening in the anterior and posterior directions is significant
      and in which severe contraction of the helix is observed. In this report, we
      describe the operative procedures used and present the relatively favorable
      results obtained in three patients. Using these techniques, we have been able to
      elongate the contracted helix frequently observed in cases of cryptotia by
      preparing a flap in the anterior auricular region. This approach appears to be a
      useful and safe means of treating cryptotia and so-called constricted ear as
      well.

PMID- 7624425
TI  - The business acumen of Canadian plastic surgeons.
AB  - We as plastic surgeons are engrossed and consumed by our quest to optimize
      patient care. In so doing, we are often distracted by that aspect of our practice
      which has direct bearing on patient care yet for which we are the least prepared-
      the business aspect. The entire population of Canadian plastic surgeons was
      surveyed in an effort to establish real and perceived needs of this group with
      respect to the business management of their practices. The survey elicited
      demographic information, information on business educational background,
      interest, and current commitment in acquiring business knowledge, and a final
      category of questions dealing with how well these surgeons function as business
      managers. Of the 315 plastic surgeons surveyed, 122 (39 percent) responded,
      which, in and of itself, indicates an interest in this aspect of their practices.
      Twelve respondents were excluded from the study for various reasons. Eighty of
      the 110 remaining respondents (72 percent) used a hospital-integrated facility
      for both emergency and elective outpatient procedures. Eighty-four of the 110
      respondents (76 percent) indicated that 10 percent of their hours per week of
      inpatient booked operating time was canceled. Ninety-three percent of respondents
      felt that a business course to familiarize surgeons with common business
      situations and areas of personal finance would be beneficial. Few were previously
      educated in business, and similarly, few had great ongoing interest in business,
      although the majority of respondents used publications specifically dealing with
      financial matters (provided by the Canadian Medical Association). Twenty-three
      percent of respondents saw themselves in a growing role as businesspeople; 24
      percent felt this dual role was enjoyable, while 29 percent felt this role was
      forced on them. A total of 21 percent of respondents did not see themselves as
      businesspeople at all. The six basic functions of a manager (planning, acquiring,
      organizing, actuating, controlling, and evaluating) were all made use of by these
      practicing surgeons, although the evaluating and controlling functions seemed to
      predominate managerial time. These surgeons do recognize, for the most part, that
      a surgical practice is a form of business enterprise as well as a professional
      endeavor. Patient care, which is of paramount importance, is affected by the
      business aspect of our practices. The Canadian plastic surgeons surveyed have
      expressed the lack of business education and training as a problem. In the
      present medical environment, we need to be more responsible and efficient in our
      business practices through education and training in this aspect of our
      practices.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7624426
TI  - Textured-surface breast implant capsules.

PMID- 7624427
TI  - Median cleft with syndactylism of the foot.

PMID- 7624428
TI  - Ullrich-Noonan syndrome.

PMID- 7624430
TI  - Editor(s), heed thyself and reply.

PMID- 7624431
TI  - Mary Shelley's Frankenstein.

PMID- 7624429
TI  - The free-fillet flap for reconstruction of the upper extremity.

PMID- 7624432
TI  - Mandibular reconstruction with osseointegrated implants.

PMID- 7624433
TI  - Subperiosteal face lift.

PMID- 7624434
TI  - Large basal cell carcinoma in a black patient.

PMID- 7624435
TI  - Nerve graftings and end-to-side neurorrhaphies connecting the phrenic nerve to
      the brachial plexus.

PMID- 7624436
TI  - Computer imaging the easy way.

PMID- 7624437
TI  - McGhan style 410 anatomic breast implant.

PMID- 7624438
TI  - Men, earrings, and keloids.

PMID- 7624439
TI  - Late fracture of an alloplastic reconstruction.

PMID- 7624440
TI  - Possible association between fibrous capsular contractures and Sansert.

PMID- 7624442
TI  - The wonderbra syndrome.

PMID- 7624441
TI  - Life-threatening hemorrhage from an ischial pressure sore.

PMID- 7624443
TI  - Production of chitinase by Pseudomonas aeruginosa K-187 using shrimp and crab
      shell powder as a carbon source.
AB  - Shrimp and crab shell powder prepared by treating shrimp and crab processing
      waste with boiling and crashing was used as a substrate for isolating alkali
      tolerant chitinolytic microorganisms. Strain K-187 appeared to be the chitinase
      producing strain with the most potential. The organism was identified as a strain
      of Pseudomonas aeruginosa. Maximum chitinase activity was obtained when the
      strain was grown aerobically in a medium consisting of 3.0% shrimp and crab shell
      powder, 0.1% CMC, 0.1% (NH4)2SO4, 0.1% K2HPO4, 0.1% MgSO4.D7H2O and 0.1% ZnSO4
      (pH 9), at 45 degrees C after 3 days. The optimum pH and temperature of the
      enzyme reaction were 7 and 40 degrees C, respectively. The chitinase was stable
      at pH from 5 to 10 and was stable under 60 degrees C.

PMID- 7624444
TI  - Construction of lysine-producing strains by gene disruption and replacement in
      Brevibacterium divaricatum.
AB  - Gene disruption and replacement techniques were applied to block the biosynthesis
      of threonine and methionine and thus to construct genetically stable lysine
      producers in a glutamate-producing bacteria, Brevibacterium divaricatum. The
      homoserine dehydrogenase gene (hom), homoserine kinase gene (thrB) and hom-thrB
      operon were amplified as 1.8, 1.25 and 2.8 kb fragments from B. divaricatum by
      polymerase chain reaction (PCR) and cloned in an E. coli-coryneform bacteria
      shuttle vector, pSUMN18. These genes were disrupted by inserting a kanamycin
      resistant gene (kan) from pUC4-KISS into the structural genes. Integrative
      plasmids were constructed and transformed into B. divaricatum. Integrative
      transformants could be obtained only when the integrative plasmids were
      constructed from the plasmids which had escaped from the restriction barrier of
      the hosts. The resulting integrative transformants showed kanamycin resistance
      and contained no plasmids. About 1-10% of the transformants were auxotrophs. By
      checking the nutritional requirement, it was found that all of these
      transformants required threonine and/or homoserine as expected. Southern blot
      analysis confirmed the integrations, and both single and double crossover
      homologous recombination mechanisms were proposed to explain the integration and
      replacement. These auxotrophic integrative transformants which were derived from
      double crossover events accumulated 1-3% lysine in culture broth only when the
      added threonine was limited. Integrative transformants which were site
      specifically inactivated in hom or hom-thrB genes produced more lysine than did
      those only inactivated at the thrB gene. These transformants were extremely
      stable, and the reversion frequency was below 10(-9) per generation. It is
      suggested that this technique will be useful in the construction of stable
      auxotrophic mutants.

PMID- 7624445
TI  - HLA DQA1 genotypes and its interaction with HLA DQB1 in Chinese IDDM living in
      Taiwan.
AB  - To study the role of the HLA DQA1 gene and its interaction with DQB1 in the
      susceptibility of IDDM, subjects with insulin-dependent (type 1) diabetes
      mellitus and non-diabetic unrelated controls were recruited from a Chinese
      population living in northern Taiwan. HLA DQA1 exon 2 was enzymatically amplified
      by polymerase chain reaction. HLA DQA1 alleles were diagnosed by dot blotting and
      hybridization with 11 sequence-specific oligonucleotide probes. Among all the
      DQA1 alleles, DQA1*0301 and DQA1*0501 were more frequent while DQA1*0102,
      DQA1*0103 and DQA1*0601 were less frequent in Chinese with IDDM than in controls.
      Among the DQA1 genotypes, only DQA1*0301/0301 and DQA1*0301/0501 were associated
      with increased risk to IDDM while DQA1*0301/0601 and DQA1*0102/0103 were
      protective against IDDM in our population. As the cell surface HLA DQ molecules
      were formed from each DQA1 and DQB1 alleles either in cis- or trans-position, the
      numbers of susceptible HLA DQ alpha beta heterodimers were then derived from the
      genotypes of HLA DQA1/DQB1 in each person. The numbers of the possible
      diabetogenic DQ alpha beta dimers correlated with the degree of risk to IDDM (r =
      0.92) but were not statistically significant (p > 0.05). Subjects with absence of
      diabetogenic HLA DQ molecules were resistant to developing IDDM while subjects
      with two or more forms of diabetogenic DQ molecules were associated with
      increased risk to IDDM. In conclusion, both DQA1 and DQB1 genes, which determine
      the formation of susceptible DQ alpha beta heterodimers, were significantly
      associated with IDDM in Chinese subjects living in Taiwan.

PMID- 7624446
TI  - The in vitro activity of beta-lactamase inhibitors in combination with
      cephalosporins against M. tuberculosis.
AB  - Although there are reports that the addition of a beta-lactamase inhibitor to
      ampicillin or amoxicillin greatly improves their in vitro activity against M.
      tuberculosis, there are no written reports about the antituberculosis effects of
      beta-lactamase inhibitors in combination with cephalosporins against M.
      tuberculosis. In this report, we have determined the minimal inhibitory
      concentrations (MIC) of 5 cephalosporins with or without combination with beta
      lactamase inhibitor against M. tuberculosis strains isolated from patients before
      antituberculosis treatment and checked the production of beta-lactamase by
      bacteria before this procedure. Four strains of M. tuberculosis were contaminated
      during the experiment, and all the other 16 strains hydrolyzed the nitrocefin
      disc, thus indicating a beta-lactamase producer. The MICs of cephalosporins alone
      against M. tuberculosis were 200-400 micrograms/ml for ceforanide, 100-400
      micrograms/ml for cephapirin, 400-1600 micrograms/ml for cefamandole, 200-1600
      micrograms/ml for cefotaxime, and 800-1600 micrograms/ml for ceftriaxone. After
      adding the equimolar concentrations of sulbactam, the MICs were reduced to 100
      200 micrograms/ml for ceforanide, 12.5-100 micrograms/ml for cephapirin, 100-400
      micrograms/ml for cefamandole, 25-200 micrograms/ml for cefotaxime, and 100-800
      micrograms/ml for ceftriaxone. We concluded that sulbactam enhanced the
      antituberculosis effect of cephalosporins.

PMID- 7624447
TI  - Metabolic and behavioral response in rats treated with amphetamine chronically
      with and without challenge.
AB  - Chronic amphetamine (AMPH) treatment may cause behavioral sensitization in
      animals and can be used as an animal model of psychosis. The aim of the study was
      to check the behavioral and metabolic response in this animal model. In rats
      pretreated with normal saline (NS) or AMPH, with or without AMPH challenge, the
      [14C]deoxyglucose method was employed to check the metabolic changes in 42
      regions. Behavioral testing was performed in rats with the same treatment. The
      results showed that after challenge with AMPH, glucose utilization was enhanced
      in most of the regions investigated. However, metabolic enhancement of the AMPH
      pretreated group was lower in the caudate nucleus when compared with that of the
      NS-pretreated group though the stereotypy rating was higher in the former.
      Dissociation between the metabolic enhancement and behavioral response was noted.
      Furthermore, more significant differences between the two pretreated conditions
      of glucose utilization were found with challenge than without challenge. Further
      evaluation using procedures which include advanced techniques can be applied in
      further investigation.

PMID- 7624448
TI  - Generation of lymphokine-activated killer (LAK) cell activity from malignant
      peritoneal effusions.
AB  - A generation of lymphokine-activated killer (LAK) cell activities from malignant
      peritoneal effusions was investigated in 10 patients with abdominal
      carcinomatosis. Five of the 10 patients were victims of colorectal cancers, three
      of gastric cancers, and one each of ovarian cancer and cholangiocarcinoma.
      Lymphocytes, the so-called effusion associated lymphocytes (EALs), were isolated
      from malignant peritoneal effusions by density gradient centrifugation and the
      plastic adherence method. These isolated EALs were subsequently cultured in the
      presence of recombinant interleukin-2(rIL-2), 3,000 I.U./ml, for 30 days. Natural
      killer (NK) cell activities and LAK cell activities of the freshly isolated and
      cultured EALs were examined at 0, 7, 14, and 30 days of culture by means of a
      standard 51Cr-release assay using K-562, HL-60, and autologous tumor cells as
      target cells. The NK cell activities of the freshly isolated EALs were not
      detected in any of the 10 patients. The LAK activities, however, could be
      generated in all of them, and the activities were maximal at 7 days. The longer
      the EALs remained in the culture, the weaker were the LAK cell activities. As far
      as cell growth was concerned, EALs proliferated well as long as the rIL-2 were
      present in the culture. Phenotypic analysis of the freshly isolated EALs revealed
      the presence of NK cells (22%, CD16+CD56+), T helper/inducer (18%, CD4+), T
      cytotoxic/suppressor (50%, CD8+), and B cells (8%, CD19+). After being cultured
      with rIL-2, the B lymphocytes gradually disappeared, and the T lymphocytes
      predominated with an increase in the percentage of T helper/inducer
      cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7624449
TI  - Effect of protein and starch degradation rates on rumen metabolism in Taiwan
      native goat.
AB  - Six ruminal and duodenal cannulated Taiwan native goats (body weight = 20 kg)
      were fed 35% roughage, 65% concentrate diet (crude protein = 9.5%) in a 6 x 6
      Latin square design to study the effect of the combination of 3 varying starch
      (corn) and 2 varying protein (soybeans) ruminal degradation rates on ruminal
      microbial density and ruminal nutrient digestibilities. Goats in treatment
      consisting of both rapid starch and protein ruminal degradation rates had higher
      total bacterial and protozoal numbers than did those in other treatments (p <
      0.05). The combination of rapid starch degradation rate and slow protein
      degradation rate supported the highest numbers of Holotrichs whereas the
      combination of both rapid starch and protein degradation rate supported the
      highest numbers of Entodiniomorphs. Ruminal starch digestibilities were higher
      for treatment diets with autoclaved corn than for those with raw corn whereas
      ruminal digestibility of protein was greater in diets with raw soybeans than in
      those with heated ones. Higher neutral detergent fiber digestibilities in the
      rumen were found with the raw corn rations and the raw soybean rations.

PMID- 7624450
TI  - On love and its enemies.

PMID- 7624451
TI  - Transference dimensions of biography.

PMID- 7624453
TI  - The revenge motive: a developmental perspective on the life cycle and the
      treatment process.
AB  - In this article, vengeance and other manifestations of aggression and hostility
      are differentiated, then the developmental origins and later manifestations of
      the revenge motive through the life cycle are traced. Consideration is given to
      each phase of the life cycle, each of which may impart its distinctive stamp onto
      the patient's desires for revenge. Consistent with this developmental
      perspective, it is pointed out that desires for revenge may have important
      adaptive functions, helping the patient contain anxieties associated with
      developmental tasks that have not been mastered. A brief case example is used to
      illustrate how unresolved problems from various developmental stages may lend a
      particular coloration to the patient's later vengeful motives. Also provided is
      another case history of an early adult homosexual woman. The article is concluded
      with a set of technical recommendations for working with such patients in
      psychotherapy and psychoanalysis.

PMID- 7624452
TI  - Redemption as a covert theme in psychotherapy.

PMID- 7624454
TI  - Vicissitudes of the erotized transference: the impact of aggression.
AB  - Little has been published concerning the erotized transferences which develop in
      the analyses of male patients in treatment with female analysts. Clinical
      material is presented in which a male patient developed both erotized and erotic
      transferences to his female analyst at differing times of the treatment. Using
      this material, differentiation is made between the nature of these transferences
      in relation to drive, affect, and ego functioning. It appears that the
      development of sexual transferences is more common in these cases than the review
      of the literature would suggest and that female analysts are less likely to
      report these cases than are their male colleagues. I would speculate that the
      aggressive and depreciating components of such transferences are overlooked by
      both male and female analysts. When treating opposite sex patients, male analysts
      may stress the sexual and loving nature of the transference wishes while female
      analysts may stress the wishes for nurturance, and merger.

PMID- 7624455
TI  - Why there are complementary learning systems in the hippocampus and neocortex:
      insights from the successes and failures of connectionist models of learning and
      memory.
AB  - Damage to the hippocampal system disrupts recent memory but leaves remote memory
      intact. The account presented here suggests that memories are first stored via
      synaptic changes in the hippocampal system, that these changes support
      reinstatement of recent memories in the neocortex, that neocortical synapses
      change a little on each reinstatement, and that remote memory is based on
      accumulated neocortical changes. Models that learn via changes to connections
      help explain this organization. These models discover the structure in ensembles
      of items if learning of each item is gradual and interleaved with learning about
      other items. This suggests that the neocortex learns slowly to discover the
      structure in ensembles of experiences. The hippocampal system permits rapid
      learning of new items without disrupting this structure, and reinstatement of new
      memories interleaves them with others to integrate them into structured
      neocortical memory systems.

PMID- 7624456
TI  - Speech sound acquisition, coarticulation, and rate effects in a neural network
      model of speech production.
AB  - This article describes a neural network model of speech motor skill acquisition
      and speech production that explains a wide range of data on variability, motor
      equivalence, coarticulation, and rate effects. Model parameters are learned
      during a babbling phase. To explain how infants learn language-specific
      variability limits, speech sound targets take the form of convex regions, rather
      than points, in orosensory coordinates. Reducing target size for better accuracy
      during slower speech leads to differential effects for vowels and consonants, as
      seen in experiments previously used as evidence for separate control processes
      for the 2 sound types. Anticipatory coarticulation arises when targets are
      reduced in size on the basis of context; this generalizes the well-known look
      ahead model of coarticulation. Computer simulations verify the model's
      properties.

PMID- 7624457
TI  - Risks and implications of interrupting maintenance psychotropic drug therapy.

PMID- 7624458
TI  - A double-blind study of psychosocial factors in 40-year-old women with essential
      hypertension.
AB  - Most studies on essential hypertension have been performed in men. The aim of the
      present study was to describe psychosocial characteristics of 40-year-old women
      with never-treated essential hypertension. Psychosocial factors like childhood
      traumas, economy and education were studied, and psychological assessments of
      irritability, hostility, 'John Henryism' and type A behavior pattern carried out.
      Hypertensive premenopausal women (n = 29) were compared with healthy, age
      matched, normotensive women (n = 18). Neither the women nor the examining
      physicians were aware of the subjects' blood pressure status, and the setting,
      thus, was double-blind. All women were investigated in the same phase of the
      menstrual cycle, and in a random order. The hypertensives' parents more often had
      hypotension than the normotensives'. The psychiatrist who conducted the
      interviews correctly classified the majority of subjects as either hypertensive
      or normotensive. Alexithymia and difficulties in coping with aggression were more
      prevalent among the hypertensives. Hypertensive and normotensive women did not
      differ in most of the psychosocial factors previously found to differ between
      hypertensive and normotensive men. Our data may imply that psychosocial as well
      as genetic factors may contribute differently to the etiology of essential
      hypertension in women than in men.

PMID- 7624459
TI  - Psychological and knowledge factors related to delay of help-seeking by patients
      with acute myocardial infarction.
AB  - Survival of an acute myocardial infarction (AMI) and subsequent prognosis are
      highly dependent on the time between onset of symptoms and medical intervention.
      The purpose of this study is to investigate which psychological and
      cardiovascular knowledge factors may contribute to the time the AMI patient takes
      to decide to seek medical help (patient delay). Three hundred patients took part
      in the study. They were interviewed and filled out several psychological
      questionnaires. The results show that patients who ask for medical help within
      half an hour have more cardiovascular knowledge, seek less distraction and more
      social support during the acute phase, compared to patients waiting longer. In
      general those who call soon appear to have easing thoughts in case of personal
      difficulties. They also deny their feelings of resentment to a lesser degree and
      interpret the symptoms of an AMI more often as originating in the heart. Future
      education campaigns should therefore not only address cardiovascular knowledge,
      but also coping and defense mechanisms.

PMID- 7624460
TI  - Stress in middle-aged women: influence of Type A behavior and narcissism.
AB  - The authors examined (1) strength of stress, (2) awareness of stress, and (3)
      influence of type A behavior and narcissistic personality on stress and its
      related factors in a sample of 500 middle-aged women. Compared to 400 middle-aged
      working men, the women scored lower on the type A and coping scales, suggesting
      the possibility that women with high scores on type A behavior cope better with
      stress. Moreover, type A behavior in women was related to narcissistic
      personality. The strength of stressors and stress coping in type A women are
      affected by the severity of narcissism.

PMID- 7624461
TI  - Religious psychotherapy in depressive patients.
AB  - This study was conducted to explore the outcome of psychotherapy in ethnic Malays
      with strong religious and cultural background. The patients were divided into two
      groups. The study and control groups consisted of 32 depressed patient each. In
      the study group brief psychotherapy of 15-20 sessions was attempted with the
      addition of a religious perspective, while in the control group the religious
      perspective was omitted. Patients in the study group showed more rapid
      improvement in the initial 3 months of the study period than those in the control
      group, but at the end of the 6 months the difference became nonsignificant.

PMID- 7624462
TI  - Does alexithymia in male alcoholics constitute a negative factor for maintaining
      abstinence?
AB  - The purpose of this study was to assess the prevalence of alexithymia by means of
      the Toronto Alexithymia Scale (TAS) in 60 male outpatients with alcohol
      dependence showing various durations of abstinence. Alexithymia (> or = 74 points
      on TAS) was found in 48% of subjects. In patients with a shorter duration of
      abstinence (< 1 year) both total scores of TAS as well as the scores for all
      three subscales were significantly higher than in subjects abstaining for more
      than 1 year. The findings may suggest a negative relationship between alexithymia
      and maintaining abstinence in male alcoholic outpatients.

PMID- 7624463
TI  - Correlates of somatic causal attributions in primary care patients with fatigue.
AB  - Researchers in the field of chronic fatigue in tertiary care found that patients'
      somatic (e.g. viral) explanations for their condition may lead to chronicity of
      symptoms. We studied the influence of a somatic attributional bias on outcome and
      reported symptoms in primary care patients with fatigue. We compared fatigue
      scores on a specific scale, and number of presented symptoms, in two groups of
      primary care patients with 'functional' fatigue: 75 with a high score on the
      somatic subscale of the Fatigue Attribution Scale (S-FAS), and 95 with a low
      score on the S-FAS. At the index visit, patients with low and high scores on the
      S-FAS were not different for age, sex, fatigue scores, and levels of depressive
      symptoms. Patients with high scores on the S-FAS presented significantly more
      somatic and psychological symptoms-a total of 36 symptoms for 24 patients (25.3%)
      in the low-score group, and a total of 52 symptoms for 31 patients (41.3%) in the
      high-score group. Forty-two days later, at the follow-up visit, the fatigue
      scores were similar in both groups. In primary care patients with fatigue not due
      to somatic illness or major depression, the tendency to attribute fatigue to
      somatic causes is not associated with a worse outcome, but with a higher number
      of reported symptoms.

PMID- 7624464
TI  - The relationship of cancer pain to anxiety.
AB  - The interaction between pain and anxiety in the setting of somatic illness is a
      widely recognised association. More accurate knowledge about the association and
      also about the means of assessing anxiety in a clinical setting are of use to the
      clinician. The present study used the Hospital Anxiety and Depression Scale for
      assessment of anxiety, and the set of linear analogue scales for detecting the
      presence and severity of anxiety and pain in an oncology clinic, where patients
      were undergoing active treatment for cancer. The relationship between pain and
      anxiety was found to be significant, even when the possible mediating effect of
      the variables of illness severity and age were removed. The need for detecting
      anxiety in order to plan treatment strategy is emphasised.

PMID- 7624465
TI  - Psychosocial group intervention and the rate of decline of immunological
      parameters in asymptomatic HIV-infected homosexual men.
AB  - The aim of the study was to determine changes in the rate of decline of
      immunological parameters after psychosocial group intervention. Subjects were 26
      asymptomatic HIV-infected homosexual men who participated in a cognitive
      behavioral group therapy (CBT; n = 14), or an experiential group therapy program
      (ET; n = 12), both of 15 weeks duration. The outcome measures were changes in the
      decline of CD4 cell counts, and T cell proliferative responses to anti-CD3
      monoclonal antibodies from preintervention to 24 months postintervention. No
      differences in the rate of decline of CD4 cells or T cell responses between the
      CBT and ET condition were found, and there were no significant changes in CD4
      cell count from pre- to postintervention. However, those subjects who showed
      larger decreases in distress showed a smaller decline in CD4 cell counts. While
      the rate of decline in T cell responses was significantly less after both
      interventions, a similar positive change in T cell responses was found in a
      comparison group of 149 HIV-infected men with similar demographic, psychosocial
      and immunological characteristics who did not participate in one of the
      interventions. We conclude that the psychosocial intervention programs tested
      here did not cause changes in CD4 cell decline or T cell responses and that
      decreases in distress were related to increases in CD4 cell counts.

PMID- 7624466
TI  - Perception of heart rate and blood pressure: the role of alexithymia and anxiety.
AB  - While the ability to estimate heart rate in a laboratory setting appears to be
      related to anxiety and alexithymia, it is still unclear how the ability to
      estimate blood pressure is related to these psychological measures. The
      perception of heart rate and blood pressure in 24 normotensive subjects with
      varying degrees of alexithymia and anxiety was examined. Results indicate that
      the estimation of heart rate is related to psychological characteristics, while
      the estimation of blood pressure is not. More anxious subjects perceived heart
      rate more accurately than less anxious subjects. Furthermore, high alexithymic
      subjects perceived heart rate less accurately than low alexithymic subjects. The
      accuracy of estimation of blood pressure was, however, not related to alexithymia
      or anxiety. These findings provide further evidence that blood pressure estimates
      in a laboratory setting are mainly based upon situational cues.

PMID- 7624467
TI  - Alexithymia and pathological gambling.
AB  - Alexithymia is increased in addictive disorders such as alcoholism, cocaine
      abuse, and binge eating. Pathological gambling is a form of addictive disorder
      and may be influenced by alexithymia. We examined the association of alexithymia
      (Toronto Alexithymia Scale) and pathological gambling (South Oaks Gambling
      Screen) in 1,147 young adults; 3.1% were classified as pathological gamblers.
      Alexithymia was found in 31.4% of pathological gamblers, compared to 11.1% of
      controls; both affective and cognitive aspects of alexithymia were associated
      with gambling problems. The relationship was independent of depression and
      physical illness, and was found for both sexes, but only for Caucasians.
      Alexithymia may be a risk factor for pathological gambling in some populations.

PMID- 7624468
TI  - The Mini-Mental State Examination among adult outpatients with major depressive
      disorder.
AB  - One hundred forty-eight patients, ages 18-65, with major depression were
      administered the Mini-Mental State Examination (MMSE) prior to 8 weeks of
      treatment with fluoxetine; 75 of these patients were readministered the MMSE
      following treatment. MMSE scores were not related to pretreatment severity of
      depression or to reported concentration problems and were not predictive of
      antidepressant response. Non- and partial responders had lower posttreatment MMSE
      scores than responders, men had lower posttreatment scores than women, and
      subjects over 50 had lower pretreatment scores than younger subjects, although in
      all cases, the magnitude of the differences was small and unlikely to be
      clinically important. Our results suggest that while the MMSE has been shown to
      be useful among geriatric and other depressed inpatients, it is not a sensitive
      indicator of depression severity, concentration problems, or likelihood of
      treatment response among otherwise healthy adults with major depression in an
      outpatient setting.

PMID- 7624469
TI  - Neurobiology of sudden death.

PMID- 7624470
TI  - [Treatment satisfaction and cooperation in the hospital and general practice-
      attitude of an internal medicine patient sample and physicians responsible for
      their treatment].
AB  - 54 inpatients of a medical department in a general hospital were explored at the
      end of the hospital stay and three months later about the treatment in the
      inpatient and in the outpatient setting, the threatening doctors also were asked
      about the patients' behaviour. Patients' content with the medical treatment was
      surprisingly high in both settings, but the doctors in the hospital as well as
      the home doctors had a more critical view of the cooperation with the ill. All
      these results were independent of age, social level of the ill and of some
      characteristics of the illnesses, from which the patients suffered, but some
      significant correlations were found with the emotional state of the patients.
      These results are a good base for further investigations with improved methods.

PMID- 7624471
TI  - [Psychophysical stress reactions during a psychoanalytic interview].
AB  - In 37 young volunteers analytically oriented interviews were taken and their
      effects being compared to those of conventional stressors using mental
      arithmetic. Because of their similarity to day-to-day stressors we expected
      higher cardiovascular reactions (blood pressure, heart rate and catecholamines)
      under interview situations than in mental arithmetic. Conforming this hypothesis,
      we found higher reactions in blood pressure regulation, while heart rates were
      not higher under interview situations compared to laboratory stressors.
      Epinephrine showed a qualitative difference: Only in interview situations we
      found a significant rise of 27%. Plasma cortisol also showed a rise in interview
      situations, however, smaller. We therefore suggest, that analytically oriented
      interviews are an adequate method to investigate cardiovascular reagibility in
      young hypertensive-prone persons.

PMID- 7624472
TI  - [Perceived emotional support of HIV-positive men in relation to the stage of the
      disease].
AB  - Perceived emotional support is considered important in buffering the adverse
      effects of life-threatening conditions, e.g. AIDS. The aim of the present study
      was to investigate (1) which aspects of perceived emotional support are
      associated with depression, anxiety and suicidality in patients with HIV
      infection, and (2) whether perception of emotional support is influenced by the
      stage of disease. 40 male patients with HIV-infection, most of them homosexuals
      (no drug-addicts, no signs of neuropsychiatric impairment) were investigated. A
      Perceived Emotional Support Scale, Zung's Self-rating Depression Scale and
      Spielberger's State-Trait-Anxiety Inventory were administered. To assess
      suicidality, a clinical interview was carried out. Stage of disease was
      determined according to CDC-classification and CD4-cell count. The data indicate
      that (1) aspects of perceived emotional support concerning regulation of self
      esteem in relation to a key figure are of greatest importance in predicting
      depression and state-anxiety and (2) emotional support is perceived significantly
      better in patients with low CD4-count, i.e. in those patients facing the greatest
      threat.

PMID- 7624473
TI  - [Theory-guided development and evaluation of a questionnaire concerning mental
      health].
AB  - In our study, the development of a Mental Health Questionnaire is described and
      this diagnostic instrument, which is based on historically important personality
      models, evaluated. Our purpose was to develop scales for Personal well-being,
      Regulatory competence, Self-actualization and Sense-finding ability. The items
      belonging to these theoretical constructs were analyzed both by a method of
      expert rating and statistically. A sample of n = 833 was tested (so-called
      healthy persons, patients with coronary heart disease [CHD], and patients with
      psychosomatic or neurotic disorders). Three of the mental health (MH) dimensions
      (except Sense-finding ability) were confirmed by expert rating. As expected, the
      following differences between the subgroups reached statistical significance:
      healthy persons had the highest values for MH, followed by CHD patients and
      psychosomatic/neurotic patients. Per item, CHD patients showed a characteristic
      pattern of answering. The combination of research methods we used in this study
      (i.e., theory-guided expert rating, statistical analysis, per item analysis) has
      provided results that may be important for further development of MH concepts.

PMID- 7624475
TI  - [76th German Radiology Conference. Wiesbaden, 24-27 May 1995. Abstracts].

PMID- 7624474
TI  - [Comment on the contribution by H. Willenberg on problems in classification of
      covert self-injury and development of an alternative suggestion].

PMID- 7624476
TI  - H-DNA:DNA triplex formation within topologically closed plasmids.

PMID- 7624477
TI  - A kinetic description of the calcium-activated potassium channel and its
      application to electrical tuning of hair cells.

PMID- 7624478
TI  - Intravenous coronary angiography with synchrotron radiation.

PMID- 7624479
TI  - Protein translocation at the membrane of the endoplasmic reticulum.
AB  - The process of insertion into and translocation across the ER membrane is a
      significant step in the biosynthesis of a membrane or secretory protein. This
      commits the protein to a destination within the "secretory pathway" (Palade,
      1975) and is part of a complex series of events involving protein targeting,
      translocation, maturation and sorting, which finally results in a biologically
      active protein being delivered to its correct subcellular location. The focus for
      this review has been the initial events of this process. Proteins which
      constitute at least a part of the actual translocation site across the ER
      membrane have been identified and the minimum components required to reconstitute
      ER translocation in vitro have been defined. A detailed description of the
      architecture of the ER translocation site and the molecular events occurring
      during translocation and membrane insertion remain goals for the future. The
      process occurring in vivo may be more complex since (i) each translocation site
      may only promote a single round of translocation in vitro whereas in vivo the
      sites must operate catalytically and go through many cycles of translocation and
      insertion (see Gilmore, 1993) and (ii) the in vivo requirement for a
      translocation site which is impermeable to small molecules (in order not to
      dissipate chemical gradients and the redox potential) is unlikely to be important
      for in vitro assays. Thus, other components which play a vital role in protein
      translocation and membrane insertion in vivo may remain to be identified. Our
      future aim must be to place a detailed understanding of the molecular events of
      the translocation process into the context of the normal cellular environment.

PMID- 7624480
TI  - Sexual dimorphism in the mammalian limbic system.

PMID- 7624481
TI  - In vitro electrophysiological studies of the vestibular nucleus complex.

PMID- 7624482
TI  - Restoration of brain energy metabolism as the function of sleep.

PMID- 7624483
TI  - Modelling the generation of long-term neuronal activity underlying behaviour.

PMID- 7624484
TI  - Development of identified neuronal types and of specific synaptic connections in
      slice cultures of rat hippocampus.

PMID- 7624485
TI  - Expression, control, and probable functional significance of the neuronal theta
      rhythm.
AB  - The data on theta-modulation of neuronal activity in the hippocampus and related
      structures, obtained by the author and her colleagues have been reviewed.
      Analysis of extracellularly recorded neuronal activity in alert rabbits, intact
      and after various brain lesions, in slices and transplants of the hippocampus and
      septum allow one to make the following conclusions. Integrity of the medial
      septal area (MS-DB) and its efferent connections are indispensable for theta
      modulation of neuronal activity and EEG of the hippocampus. The expression of
      hippocampal theta depends on the proportion of the MS-DB cells involved in the
      rhythmic process, and its frequency in the whole theta-range, is determined by
      the corresponding frequencies of theta-burst in the MS-DB. The neurons of the MS
      DB have the properties of endogenous rhythmic burst and regular single spike
      oscillators. Input signals ascending to the MS-DB from the pontomesencephalic
      reticular formation increase both the frequency of the MS-DB theta-bursts and the
      proportion of neurons involved in theta-activity; serotonergic midbrain raphe
      nuclei have the opposite effect on the MS-DB rhythmic activity and hippocampal
      EEG theta. Increase of endogenous acetylcholine (by physostigmine) also increases
      the proportion of the MS-DB neurons discharging in theta-bursts (both in intact
      and basally-undercut septum), but does not influence the theta-frequency. The
      primary effect of the MS-DB on hippocampal neurons (pyramidal and non-pyramidal)
      consists in GABAergic reset inhibition. Reset inhibition, after which theta
      modulation follows in constant phase relation, is triggered also by sensory
      stimuli. About two-thirds of the hippocampal pyramidal neurons are tonically
      inhibited by sensory stimuli which evoke EEG theta, while others are excited, or
      do not change their activity. Anticholinergic drugs restrict the population of
      rhythmic neurons but do not completely suppress theta-bursts in the MS-DB and
      hippocampus. Under their action, EEG theta can be evoked (presumably through
      GABAergic MS-DB influences) by strong reticular or sensory stimuli with
      corresponding high frequency. However information processing in this condition is
      defective: expression of reset is increased, responses to electrical stimulation
      of the perforant path and to sensory stimuli are often augmented, habituation to
      sensory stimuli is absent and tonic responses are curtailed. On a background of
      continuous theta induced by increase of endogenous acetylcholine, reset is absent
      or reduced, responsiveness of the hippocampal neurons to electrical and sensory
      stimulation is strongly reduced.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7624486
TI  - Molecular recognition and olfactory processing in the mammalian olfactory system.

PMID- 7624487
TI  - Magnetic resonance imaging using deoxyhemoglobin contrast versus positron
      emission tomography in the assessment of brain function.
AB  - 1. Function of the brain can be assessed through radiologic imaging to determine
      physiology of underlying tissue. 2. Until recently, positron emission tomography
      has been the standard tool with which to study function. 3. In the past few
      years, several investigators have attempted to use magnetic resonance imaging,
      which has better resolution and is less expensive, to provide functional
      information. 4. A noninvasive technique termed BOLD (blood oxygen level
      dependent) has become a popular area of research to determine physiologic change
      that occurs in the brain in resting as well as activated states. 5. This article
      reviews what information PET has given us with regard to function of the brain,
      followed by a discussion of the principle of functional MRI of the brain with
      emphasis on what has been done in this field as well as future application of the
      technique.

PMID- 7624488
TI  - Frequency of positive family history in bipolar patients in a catchment-area
      population.
AB  - 1. Major family studies of bipolar disorder report the frequency of affective
      disorder among probands' relatives, but do not usually report the frequency of a
      positive family history among probands. A single previous study was not
      population based. 2. The Division of Psychiatry of Ben Gurion University provides
      virtually all psychiatric services for a catchment area of 300,000 people. The
      authors reviewed the charts of all 236 treated bipolar I patients in 1991, and
      interviewed 177 of them with a modified FH-RDC. 3. 48% of probands had a family
      history of mental illness. 4. However, the present methods of ascertainment may
      have been insufficiently sensitive.

PMID- 7624489
TI  - Platelet markers in suicide attempters.
AB  - 1. The authors measured 3H-imipramine (3H-IMI) binding and serotonin (5HT) uptake
      parameters as well as sulphotransferase activity in platelets of suicide
      attempters. 2. Platelet 3H-IMI binding sites and 5HT uptake are related to
      similar sites and processes present in the brain, and sulphotransferase (ST) is
      an enzyme involved in the catabolism of cathecholamines. 3. The results showed
      the presence of a decreased density of both 3H-IMI binding and of 5HT uptake
      sites, with no change in ST activity in suicide attempters, as compared with
      healthy controls. 4. The reduced 3H-IMI binding and 5HT uptake may be related to
      a hypofunction of presynaptic serotonergic mechanisms which might be altered in
      suicidal behavior.

PMID- 7624490
TI  - Stimulatory effect of butoctamide hydrogen succinate on REM sleep in normal
      humans.
AB  - 1. The efficacy of butoctamide hydrogen succinate (BAHS) was compared with that
      of nitrazepam on the basis of the polysomnograms and the subjective assessments.
      2. Twelve healthy male students were divided into three groups consisting of 4
      subjects each with were administered BAHS 600 mg, nitrazepam 5 mg, and BAHS 600
      mg + nitrazepam 5 mg, respectively. 3. Polygraphic recordings were made for 8
      consecutive nights for each subject, and the polysomnograms were evaluated by
      computerized automatic analysis using the interval histogram method. 4. An inert
      placebo was administered on the first 3 nights and on the seventh and eighth
      nights, and the test article regimen was administered on the fourth, fifth and
      sixth nights. 5. The test articles and the placebo were administered orally at
      22:30 hr, and the recording of polysomnograms was started at 23:00 hr and ended
      at 8:00 hr the next morning. 6. The subjects were requested to fill out the
      subjective assessment of sleep before falling asleep and after arising the next
      morning. 7. BAHS increased REM sleep and decreased stage 2 sleep significantly;
      however, it failed to affect stage 1, 3 or 4 sleep. 8. Nitrazepam increased
      significantly the total sleep time and stage 2 sleep but decreased significantly
      the stage 3 sleep and decreased slightly the stages 1, 4 and REM sleep. 9. The
      combined treatment with BAHS and nitrazepam did not alter the sleep parameters
      except for increasing the total sleep time. 10. No obvious changes were observed
      in the subjective assessments after administration of the drugs. 11. These
      findings suggest that BAHS results in a unique sleep pattern different from
      benzodiazepines, and that BAHS may be suitable for treating insomnia in elderly
      patients and those with drug abuse, manic-depressive illness or schizophrenia.

PMID- 7624491
TI  - Flash P2 delay in primary degenerative dementia of the Alzheimer type.
AB  - 1. Flash visual evoked responses of 31 patients meeting DSM-III-R criteria for
      primary degenerative dementia of the Alzheimer type were compared with 31 healthy
      controls. 2. P1 latency was normal (75 +/- 6 msec Alzheimer's; 75 +/- 6 msec
      controls). 3. P2 was significantly delayed (162 +/- 32 msec, 147 +/- 20 msec, p <
      0.03) among patients. 4. P1-P2 interpeak latency was significantly increased (87
      +/- 32 msec, 71 +/- 21 msec, p < 0.03) among patients.

PMID- 7624492
TI  - Cognitive effects of a new pyrrolidine derivative (levetiracetam) in patients
      with epilepsy.
AB  - 1. A new pyrrolidine derivative (levetiracetam), resembling piracetam, was given
      as antiepileptic concomitant drug to patients with chronic epilepsy. 2. In a
      single-blind add-on rising-dose study the cognitive side-effects were
      investigated twice after one week of administration. 3. The results did not show
      any significant changes in cognitive performances.

PMID- 7624493
TI  - Insomnia and psychotropic drug consumption.
AB  - 1. During an epidemiological study conducted by telephone on sleep disorders in
      the metropolitan area of Montreal (Quebec, Canada), the authors found that 5% of
      subjects used psychotropic drugs. These drugs were usually prescribed by a
      general practitioner (72.9%). 2. From this population, the authors drew three
      groups of subjects: users with sleeping difficulties (USD); non users with
      sleeping difficulties (NUSD) and, non users without sleeping difficulties
      (NUWSD). 3. Results showed that the utilization of psychotropics was usually
      chronic and more frequent among the elderly and women. 4. In multivariate models,
      when users were compared to NUWSD, the authors found eight variables
      significantly associated with psychotropic consumption: age (> or = 55), sex
      (female), presence of physical illness, medical consultation, dissatisfaction
      with sleep onset period and sleep quantity, sleep onset period greater than 15
      minutes, and to never or rarely dream. 5. When users were compared to NUSD, three
      variables were found to be associated with psychotropic consumption: age, to be
      formerly married, and to experience regular nighttime awakenings. 6. It appears
      that the utilization of psychotropic drugs does not increase the quality of sleep
      when consumers are compared to non treated insomniacs (NUSD) on parameters of
      sleep satisfaction.

PMID- 7624494
TI  - REM latency, dexamethasone suppression test, and thyroid releasing hormone
      stimulation test in posttraumatic stress disorder.
AB  - 1. Twenty-one patients with post-traumatic stress disorder (PTSD) were included
      in a study utilizing baseline rapid eye movement (REM) latency measurements, the
      dexamethasone suppression test (DST), and the protirelin (thyroid releasing
      hormone; TRH) stimulation test. The DST and TRH stimulation test were repeated
      after double blind treatment with desipramine. 2. A high number of patients (75%)
      exhibited a REM latency of 60 min or less and blunted thyroid stimulating hormone
      (TSH) response to TRH (61.9%) on baseline tests while only one patient showed
      cortisol escape from dexamethasone suppression. 3. After four weeks of
      desipramine treatment, significant improvements were reported in the Hamilton
      Rating Scale for depression, but not for anxiety symptoms, PTSD symptoms, or self
      rated depressive symptoms. 4. Desipramine treatment did not affect hormonal
      responses to TRH. 5. The findings of shortened REM latency and altered TRH
      stimulation test suggest PTSD and depression may share some pathophysiological
      abnormalities.

PMID- 7624495
TI  - The effect of sleep deprivation on motor impairment and retinal adaptation in
      Parkinson's disease.
AB  - 1. Sleep deprivation has previously been reported to result in a temporary
      improvement of motor deficits in Parkinson's disease patients. 2. The mechanism
      of this action is unclear but may involve an activation of dopamine pathways. 3.
      Other studies suggest that light adaptive changes in the retinal pigment
      epithelium may serve as a model of dopamine sensitivity. 4. The present study
      examined the effects of one night of total sleep deprivation on RPE potentials
      and motor abnormalities in Parkinson's patients. 5. Sleep deprivation
      significantly improved motor deficits and these changes were strongly correlated
      with increases in light adaptive RPE potentials.

PMID- 7624496
TI  - World wide use of psychotropic drugs in child and adolescent psychiatric
      disorders.
AB  - 1. Questionnaires were mailed to child psychiatrists world wide to obtain more
      precise information on views and approaches to the diagnosis and treatment of
      childhood psychiatric disorders. 2. Results indicated important problems related
      to the management of child psychiatry practice both overseas and in Canada. 3.
      The choice of medication was frequently restricted by lack of availability, and
      political or social attitudes. 4. A consensus on diagnosis and treatment
      guidelines in child and adolescent psychiatry remains an important issue.

PMID- 7624497
TI  - Effects of D-amphetamine administration on the release of endogenous excitatory
      amino acids in the rat nucleus accumbens.
AB  - 1. The effects of acute D-amphetamine administration to rats on the release of
      endogenous excitatory amino acids from nucleus accumbens slices were studied. 2.
      D-amphetamine (5 mg/kg and 10 mg/kg; i.p.) significantly increased the
      spontaneous release of aspartate and glutamate from nucleus accumbens slices. 3.
      In contrast, D-amphetamine either produced no change or rather decreased K+ (40
      mM)-evoked and N-methyl-D-aspartate (100 microM)-evoked release of aspartate and
      glutamate from the slices, respectively. 4. When D-amphetamine treated rats were
      pretreated with haloperidol, the effects of D-amphetamine on the spontaneous
      release of excitatory amino acids were not produced, whereas its effects on N
      methyl-D-aspartate-evoked release remained unchanged. 5. These data suggest that
      amphetamine produces changes in excitatory amino acid-mediated transmission in
      the nucleus accumbens, that may play a role in amphetamine-induced behavioral or
      psychotomimetic effects.

PMID- 7624498
TI  - Effects of naloxone on the behaviors evoked by amphetamine and apomorphine in
      adult cats.
AB  - 1. This work was undertaken in order to study whether the opioid system is
      involved in the modulation of the behaviors induced by two agonists of the
      dopaminergic system, amphetamine and apomorphine in adult cats. 2. Naloxone, an
      antagonist of the mu, delta and kappa opioid receptors was administered to twelve
      female mongrel cats; 0.5, 1.0 and 2.0 mg/kg s.c. were injected in order to
      analyse its own effect of naloxone. This drug produced NREMs behavior and
      accordingly the cat showed an overall decrease of its activities. 3. Amphetamine
      (2.5 mg/kg s.c.) and apomorphine (2.0 mg/kg s.c.) were injected before and after
      naloxone administration (2.0 mg/kg s.c.), in separate sessions. 4. The behaviors
      recorded were compared. Some of the behaviors showed modifications both with
      amphetamine (inappetence was increased and locomotion decreased) and apomorphine
      (indifference and inappetence increased; locomotion and olfaction decreased). 5.
      These changes were considered as consequence of the NREMs behavior induced by
      naloxone and not as a result of a modulation by the opioid system of the
      activation of the dopaminergic system elicited by amphetamine and apomorphine.
      Regarding the mechanism of NREMs induced by naloxone probably the dopaminergic,
      noradrenergic and GABAergic systems may be involved.

PMID- 7624499
TI  - Progesterone releases dopamine in male and female rat striatum: a behavioral and
      microdialysis study.
AB  - 1. The acute effect of progesterone at a physiological dose (50 micrograms) was
      investigated behaviorally by measuring postural deviation of rats bearing a
      unilateral lesion of the entopeduncular nucleus and biochemically by in vivo
      microdialysis in the striatum. 2. Ovariectomized female and intact male rats
      displayed a significant increase of postural deviation to the lesioned side 30-65
      min after the subcutaneous injection of progesterone with a return to control
      values thereafter. 3. In addition, rats of both sexes had increased dopamine (DA)
      in the first 20-40 min dialysate collection following the progesterone injection.
      The metabolites of DA dihydroxyphenylacetic acid (DOPAC) and homovanillic acid
      (HVA) in the dialysate were also increased after the progesterone injection and
      HVA levels remained elevated for a longer time than DA, up to 120 min after
      progesterone. 4. Progesterone, at a physiological dose and independently of
      estrogens can therefore rapidly increase DA release in the striatum of rats of
      both sexes as revealed in vivo behaviorally and biochemically.

PMID- 7624500
TI  - Scopolamine-physostigmine combination does not substitute for nicotine.
AB  - 1. Male Sprague-Dawley rats were trained to discriminate 0.4 mg/kg nicotine
      subcutaneously administered from its saline vehicle in a food-motivated operant
      discrimination task. Once trained, the discriminative performance was observed to
      be dose-responsive with an ED50 = 0.11 mg/kg. 2. The co-administration of 0.1 or
      0.2 mg/kg physostigmine with either 0.1, 0.15 or 0.2 mg/kg scopolamine produced
      intermediate discriminative effects, i.e., neither nicotine- nor saline-like
      responding. However, the physostigmine-scopolamine combination neither
      substituted for nor increased the discriminative effects of co-administered
      nicotine. 3. The theoretical/mechanistic possibility that a combination of a
      cholinesterase inhibitor to increase available acetylcholine plus a specific anti
      muscarinic to allow that increased acetylcholine to stimulate nicotinic receptors
      was investigated. Results indicate that the combination does not produce nicotine
      like discriminative effects and evidence the possibility that nicotine
      discrimination may involve non-cholinergic mechanisms.

PMID- 7624501
TI  - Endothelin-1-like immunoreactivity in cerebral cortex of Alzheimer-type dementia.
AB  - 1. Endothelin-1-like immunoreactivity (ET-1-LI) in cerebral cortex in postmortem
      brains obtained from patients with Alzheimer-type dementia (ATD) was measured by
      enzyme-immunoassay. 2. The ET-1-LI in the ATD brains was significantly increased
      in frontal and occipital cortex than those in the control brains and a
      significant correlation was found between frontal and temporal lobe of ATD
      brains. 3. These findings may explain the clinico-radiological results that the
      cerebral blood flow is decreased in ATD patients, the mechanism of which is still
      unknown.

PMID- 7624502
TI  - The treatment of refractory depression using paroxetine with lithium
      augmentation.
AB  - 1. The case is described of a 68-year-old woman with DSM-III-R major depression
      who was treatment-resistant to paroxetine. 2. Low dose lithium addition, at a
      plasma level of 0.2 mM, led to a rapid and sustained remission of her illness.

PMID- 7624503
TI  - Effectiveness of the combination verapamil and chlorpromazine in the treatment of
      severe manic or mixed patients.
AB  - 1. The authors investigated the possible antimanic properties of a Calcium
      channel blocker, Verapamil, in 15 in-patients admitted consecutively to the
      female psychiatric ward at Pisa University for a manic episode. 2. The results
      showed that most of the patients presented a global improvement of the manic
      symptoms and, in some cases, even a complete clinical remission. 3. Although it
      was necessary to add chlorpromazine for the severe conditions of several
      patients, verapamil appeared to speed the positive outcome and to lead to a
      faster resolution of the symptoms. In addition, the association of verapamil and
      chlorpromazine did not produce any relevant side-effect. These preliminary
      findings thus indicate that verapamil by itself does not seem to be sufficient in
      the treatment of a severe affective episode, but it may constitute an alternative
      to lithium salts in association with neuroleptics.

PMID- 7624504
TI  - The teaching of the biological basis of psychiatry.
AB  - 1. What is usually taught as biological psychiatry in psychiatric residency
      training is mainly psychopharmacology, but biology has a lot more to offer to
      psychiatry educators. 2. The main thesis of this article is that an introductory
      course on the applications to psychiatry based on the theory of the evolution of
      the species by natural selection and mutation, along with a comprehensive theory
      of mind, may contribute to: (i) helping young physicians to integrate the diverse
      and extensive knowledge acquired during the residency training; (ii) aid in
      keeping the psychiatrist within the medical approach to mental illnesses while
      promoting the specific features of the specialty, and (iii) perhaps developing a
      general theoretical framework that allows psychiatrists to maintain a prominent
      role in the mental health staff. 3. The author describes how he has conducted
      such training in Venezuela. It is expected that the author's ideas will serve as
      a forum for discussion of this pivotal subject.

PMID- 7624505
TI  - The metabolism of glutamine by the preimplantation sheep conceptus and its
      interaction with glucose.
AB  - The metabolism of glutamine and glucose, separately and in combination, by the
      sheep conceptus recovered on Days 2, 6, 13, 15, 17, and 19 of pregnancy was
      assessed over 2.5 h. At Day 2, the production of CO2 from glutamine was similar
      to that from glucose, with additive effects seen when both substrates were
      present. Between Day 2 and Day 6, there was a three-fold increase in glucose
      oxidation but no change in the oxidation of glutamine. From Day 13 to Day 19, the
      oxidation of glutamine was relatively high in embryonic tissue, low in
      trophoblastic tissue and intermediate in the yolk sac but in all tissues
      decreased as development progressed. Over this latter period the oxidation of
      glutamine was reduced to approximately 50% by the addition of glucose to the
      medium but glucose oxidation was unaffected by the addition of glutamine. At the
      early stages of development, the incorporation of substrate carbon from glutamine
      was less than that from glucose but in each case, incorporation into the acid
      insoluble macromolecular fraction increased 2-3 times between Day 2 and Day 6.
      Incorporation of glutamine into the Day-17 and Day-19 conceptus was also
      measured; embryonic tissue exhibited the highest rate of incorporation and
      trophoblastic tissue the lowest. Incorporation was lower on Day 19 than on Day 17
      and the proportion of carbon isolated in the acid-insoluble fraction represented
      20% of the total incorporated. At no time did the addition of glucose to the
      medium alter incorporation of glutamine into either embryonic tissue or
      extraembryonic membranes.

PMID- 7624506
TI  - Temporal changes to uterine collagen types I, III and V in relation to early
      pregnancy in the rat.
AB  - Uterine tissues of pregnant rats were extracted to define any changes to the
      proportions of collagens types I, III and V. The total concentration of extracted
      collagen was determined in tissue samples from implant and adjacent non-implant
      (NI) sites. Extracts were also subjected to polyacrylamide gel electrophoresis
      (PAGE), immunoblotting and gel densitometry to define the collagen types and to
      determine their relative proportions. By relating the proportions to the collagen
      concentrations in the extracts, type I was found to be the predominant collagen
      in both tissue regions although the concentration in the implant sites was lower
      than that in the NI sites. The concentration of Type I collagen decreased
      significantly over the period of observation in both implant and NI sites.
      Although the concentrations of collagen type III and type V also decreased in the
      implant sites, they did not alter in the NI sites. The results demonstrate that
      shortly after the initiation of implantation the uterus responds to the presence
      of the implanting embryo by decreasing the concentration of all three types of
      collagen. This indicates that their metabolism may, in part, be regulated by
      similar mechanisms. Furthermore, it was evident that a decrease in the
      concentration of collagen type I was initiated in uterine areas that, at the time
      of sampling, were not directly involved with implantation. During the study, it
      was found that the alpha 1 chain of collagen type V separated into two distinct
      bands when run on gels containing 3.8 M urea.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7624507
TI  - Association of glycerylphosphorylcholine with human sperm and effect of
      capacitation on their metabolism.
AB  - The presence and localization of glycerylphosphorylcholine (GPC) on the surface
      of human sperm, as well as the metabolism of its breakdown product L-glycerol 3
      phosphate (G3P), were investigated. GPC was found to be associated with sperm
      after penetrating cervical mucus and was present after repeated washing of the
      sperm. GPC was partially released by treatment with 0.4 M NaCl in 0.01 M sodium
      phosphate buffer (pH 7.4) and localized to the head region after sperm
      fractionation. G3P did not increase O2 uptake of uncapacitated human sperm.
      However, under aerobic conditions, lactate accumulated when exogenous G3P or
      uterine GPC diesterase was added to sperm in suspension. The uptake of O2 by
      washed capacitated sperm pre-incubated with 1 unit of rat uterine GPC diesterase
      for 30 min was significant. This effect was inhibited by 2 microM oligomycin
      indicating that oxidative phosphorylation had occurred. The present study
      indicates that GPC may play a role in the metabolism of human sperm after
      capacitation.

PMID- 7624508
TI  - Induction of cyclooxygenase and prostaglandin E2 production by the bovine pre
      embryo.
AB  - A study was conducted to determine the induction of cyclooxygenase production in
      the cleaved and non-cleaved oocyte and to measure the secretion of prostaglandin
      E2 (PGE2), PGF2 alpha and tumour necrosis factor-alpha (TNF alpha) in the
      conditioned medium of non-mature oocytes (denuded), mature oocytes (oocyte
      cumulus complex), cleaved oocytes, and non-cleaved oocytes (mature oocytes
      incubated in the absence of sperm). Cyclooxygenase was readily detectable in 48-h
      cleaved oocytes whereas the signal for the enzyme in the non-cleaved oocytes was
      weak or undetectable. Cyclooxygenase expression in the cleaved oocytes was
      transient and enzyme concentrations at the early morula stage (72 h) were low.
      Measurable amounts of both PGE2 and TNF alpha were secreted during the first 24 h
      of maturation and 6 h after fertilization, whereas PGF2 alpha was undetectable at
      these times. There was a dramatic enhancement in PGE2, PGF2 alpha and TNF alpha
      secretion 48 h after fertilization. At 72 h after fertilization, PGE2
      concentrations were much lower and PGF2 alpha was again undetectable which
      corresponded to a low concentration of cyclooxygenase. In contrast, high TNF
      alpha activity continued to be detected even 72 h after fertilization. It is
      possible that the induction of the production of cyclooxygenase and the secretion
      of PGs and TNF alpha by fertilized oocytes at specific times after fertilization
      plays a role in the regulation of embryonic development, maternal immunological
      recognition of pregnancy, and the maintenance of a suitable hormonal environment
      for embryonic viability.

PMID- 7624509
TI  - Stimulatory and inhibitory factors of Leydig cell steroidogenesis are secreted
      simultaneously by the rat seminiferous tubules and do not affect Leydig cell
      inhibin production in vitro.
AB  - The effect of conditioned medium from rat seminiferous tubules (at Stages VII
      VIII and Stages IX-VI) cultured with or without follicle-stimulating hormone
      (FSH) on the production of testosterone and immunoactive inhibin by Leydig cells
      was examined. Low doses of conditioned medium from unstimulated tubules at Stages
      VII-VIII significantly (P < 0.05) increased the mean testosterone production to
      greater than 31 +/- 11% over that achieved with luteinizing hormone (LH) alone.
      At the highest dose, the conditioned medium significantly inhibited (P < 0.05) LH
      stimulated testosterone production by 13 +/- 7%. Low doses of conditioned medium
      from unstimulated tubules at Stages IX-VI increased the mean testosterone
      production to 22 +/- 10%, whereas at higher doses, a significant reversal in the
      stimulation occurred although not to the same extent as that found with medium
      from tubules at Stages VII-VIII. Conditioned medium from FSH-stimulated tubules
      at Stages VII-VIII and Stages IX-VI, significantly increased testosterone
      production to 39 +/- 7% and 31 +/- 13% respectively. Immunoactive inhibin
      production by the Leydig cells remained unaffected by exposure to conditioned
      medium from FSH stimulated and unstimulated tubules at Stages VII-VIII and Stages
      IX-VI. The data demonstrate that tubule culture medium contains FSH-modulated
      activities which can specifically stimulate and inhibit testosterone synthesis by
      adult rat Leydig cells in vitro and therefore explains the contradictory reports
      in the literature.

PMID- 7624510
TI  - Spermatogenic cells and stages of the seminiferous epithelial cycle in the Indian
      gerbil field rat, Tatera indica.
AB  - Four types of spermatogonia (A0, A, In, B) are distinguished in T. indica. Four
      generations of A type, a single generation of intermediate (In) and two
      generations of B type spermatogonia are identified. Seven divisions of
      spermatogonia have been observed, in Stages 1b, 2b, 3b, 4b, 5, 6 and 7
      respectively. Spermatocytes have been observed in prophase, metaphase, anaphase
      and telophase; in terms of size and morphology, the phases of prophase could be
      further divided. Pre-leptotene and leptotene appear in Stage 8 and Stage 1
      respectively. Round spermatids become asymmetrical in Stage 1b. For the first
      time in rodents, Stages 1, 2, 3, 4 and 8 have been subdivided. The percentage
      frequencies of Stages 1-8 are 12.93, 10.69, 17.54, 10.33, 3.76, 11.20, 7.88 and
      25.67 respectively. Although the morphology of the spermatogenic cells and
      associations of these cell types are basically similar to those in albino rats,
      T. indica markedly differs from all other rodents studied in having two
      generations of B spermatogonia and subdivisions of Stages 1, 2, 3, 4 and 8; in
      addition, the relative frequencies of the stages distinctly differ from those
      recorded in previous studies of rats. Hence, the durations of different cell
      types in T. indica may differ markedly from those in other rodents.

PMID- 7624511
TI  - The effects of bromocriptine on lactation and subsequent reproduction in grey
      kangaroos, Macropus fuliginosus and Macropus giganteus.
AB  - Both species of grey kangaroo were tested to determine whether a single exposure
      to bromocriptine in mid winter will terminate lactation, and whether females that
      cease to lactate will return to oestrus immediately and give birth early, or at
      the next summer breeding season. In Experiment 1, 11 lactating western grey
      kangaroos (Macropus fuliginosus) received injections either of saline (n = 2) or
      of bromocriptine at dose rates of 0.2, 1.0 or 5.0 mg kg-1 bodyweight (n = 3 per
      dose). Pouch young of females treated with the highest dose of bromocriptine
      showed either retarded growth or no growth, but they subsequently survived. In
      Experiment 2, lactating western (n = 12) and eastern grey kangaroos (M.
      giganteus) (n = 14) received a single intramuscular injection of saline or
      approximately 2 mg kg-1 or 4 mg kg-1 Parlodel LA (a long-acting form of
      bromocriptine) and their young were weighed. Within 3 weeks, the young of all 19
      females treated with Parlodel LA had lost weight and 17 had died, whereas only
      one young, which had not lost weight, was lost from the seven control females.
      The western grey females did not give birth until the normal summer breeding
      season but the eastern grey females gave birth 2-4 months early. It is concluded
      that bromocriptine has potential for the humane control of grey kangaroo
      populations.

PMID- 7624512
TI  - Variation in reproductive parameters in the captive male koala (Phascolarctos
      cinereus).
AB  - Plasma androgen concentration was measured in six mature male koalas over 23
      months. During this time, four animals were housed isolated from females.
      Androgen concentration showed a seasonal change, with a nadir about the middle of
      the year, and began to increase sometime before the start of the breeding season.
      The concentration was greater when males were housed with females, even when the
      females were not yet cycling themselves. Changes in androgen concentration were
      not associated with changes in testicular volume. When plasma extracts were
      examined following separation by high pressure liquid chromatography, the major
      circulating androgen was testosterone with only trace amounts of 5 alpha
      dihydrotestosterone present. Plasma androgen fluctuated during the day suggesting
      some form of diurnal rhythm of secretion. Two further animals were fitted with
      vascular access ports to allow more frequent blood collection and samples were
      taken every second day for two months, a period that included a major portion of
      the breeding season. Androgen concentration fluctuated widely from 0 nmol L-1 to
      20 nmol L-1 over successive sampling and indicating an episodic pattern of
      secretion. Plasma cortisol concentration was measured in all animals in these
      studies to monitor stress and remained low except when animals were undergoing
      surgery, were being moved to different enclosures or were exhibiting reproductive
      behaviours. Overall, there was no significant correlation between the
      concentration of androgen and cortisol in plasma (n = 215). This contrasted with
      a group of wild-bled animals (n = 4) where there was a highly significant
      negative correlation.

PMID- 7624513
TI  - Low MHC class II variability in a marsupial.
AB  - The major histocompatibility complex (MHC) loci have been shown to be highly
      polymorphic in most eutherian ('placental') species studied. Several hypotheses
      have been advanced for the maintenance of this exceptional level of genetic
      variation, one of which suggests that it is necessary for successful eutherian
      reproduction. Marsupials (metatherians) and eutherians are the only two groups of
      viviparous mammals, but their modes of reproduction are quite distinct. Although
      marsupials have placentae, they are generally shorter lived and less invasive
      than in eutherians. Other investigations have shown that genetic variation at
      marsupial MHC class I loci is probably high. Weak or non-existent mixed
      lymphocyte culture responses previously reported in several marsupial species
      have suggested a lack of class II variation. Data have therefore been collected
      on the level of restriction fragment length polymorphism at MHC class II beta
      chain encoding loci of a marsupial, Macropus eugenii (the tammar wallaby). This
      level is shown to be low, between the level of MHC variation found in cheetahs
      and a population of lions with a restricted genetic base. Attention is drawn to
      the need to collect more data on the level of class II variability in both
      eutherians and marsupials, and to the potential of marsupials for understanding
      the relation, if any, between mode of reproduction and MHC variability.

PMID- 7624514
TI  - Testicular and epididymal sperm content in grazing Cashmere bucks: seasonal
      variation and prediction from measurements in vivo.
AB  - Each month, for 15 months, the testes and epididymides were recovered from five
      Australian cashmere bucks selected at random from a group of mature bucks
      (initial n = 116) at pasture (location 29 degrees S, 153 degrees E). The extent
      of seasonal change in testicular and epididymal sperm reserves was determined and
      indirect methods for predicting these reserves were developed. Paired testicular
      weight exhibited clear seasonal variation from 137 g in August to 269 g in
      February. The total elongated spermatid content of the testes, determined by
      homogenization, showed a very similar seasonal pattern, ranging from 13.8 x 10(9)
      in September to 36.2 x 10(9) in March. Seasonal changes of similar timing were
      observed for paired epididymal weight and sperm content. Although changes in
      total testicular spermatid content were largely the result of change in
      testicular weight (R2 = 0.72, P < 0.001), the elongated spermatid content of
      testicular parenchyma (mean, 127 x 10(6) g-1) exhibited significant seasonal
      variation with elevated values between February and June, suggestive of an
      increase in the efficiency of spermatogenesis. Daily sperm production, calculated
      by means of a spermatogenic time divisor for sheep, ranged from 2.76 x 10(9) in
      September to 7.23 x 10(9) in February. Scrotal circumference, scrotal volume and
      testicular length x diameter2 were identified as accurate predictors of
      testicular weight (R2 > or = 0.87) and sperm content (R2 > or = 0.70). The
      results demonstrate that: (a) cashmere bucks exhibit considerable seasonal
      variation in spermatogenesis associated primarily with changes in testicular mass
      but also with changes in the efficiency of spermatogenesis; and (b) indirect
      measures of testicular size are good predictors of testicular elongated sperm
      content. When the correct spermatogenic time divisor for goats is determined,
      such indirect measures may be used to predict daily sperm production.

PMID- 7624515
TI  - Ovulatory activity, hormonal induction of ovulation and fertility of young
      Cashmere and Angora female goats in a temperate environment.
AB  - Reproductive parameters of young Cashmere and Angora goats born between 1988 and
      1990 and grazed on temperate pastures in southern Australia were examined with a
      view to reducing the age of first breeding. Females born in August or October of
      1989 and 1990 were examined each month by laparoscopy to determine natural
      ovulatory activity when 6-19-months old. Cashmeres commenced ovulating as young
      as 7 months of age or as light as 12 kg. Almost all Cashmeres were ovulating by 8
      10 months of age at a liveweight of at least 18 kg, and their breeding season
      extended from April to October. By comparison with Cashmeres, Angoras grew more
      slowly, fewer ovulated, they commenced ovulation later, their ovulation rates
      were lower and their breeding season was shorter. A stratified sample of these
      females was injected with 200 I.U. or 400 I.U. of pregnant mare serum
      gonadotrophin (PMSG) after treatment with controlled internal drug release (CIDR)
      devices for 16-18 days to induce ovulation at 6, 9, 12, 15 and 19 months of age.
      Ovulation rates after CIDR-PMSG treatment were higher for Cashmeres than for
      Angoras and tended to be higher for females injected with 400 I.U. PMSG than 200
      I.U. PMSG. The proportion of females remaining anovulatory after exogenous
      hormonal treatment was higher for Angoras than for Cashmeres (38% and 10%
      respectively) but it was not affected by the dose of PMSG or age. For kids born
      in 1989, the kidding rates to insemination (with follow-up mating) after CIDR
      PMSG treatment for 8-month-old and 20-month-old Cashmeres (in the breeding
      season) were similar (75.0% and 83.8% respectively) but the rate for 14-month-old
      Cashmeres was only 10.0% (in the non-breeding period). The kidding rates for
      Angoras bred at 8, 14 and 20 months of age were 8.4%, 20.0% and 30.0%
      respectively. Ovulatory activity and fertility in the non-breeding period, with
      or without CIDR-PMSG treatment, did not improve with melatonin treatment.

PMID- 7624516
TI  - Immunocytochemical localization and changes in endometrial progestin receptor
      protein during the porcine oestrous cycle and early pregnancy.
AB  - Changes of progesterone receptor (PR) protein and cellular localization in the
      endometrium were evaluated during the oestrous cycle and early pregnancy of the
      gilt. During the oestrous cycle, the concentration of total PR protein within the
      endometrium was highest on Days 0-5 and decreased on Day 10. The endometrial
      concentration of PR reached a nadir on Day 12 and this level was maintained
      throughout the remainder of the oestrous cycle (Day 18). In pregnant gilts, the
      concentration of endometrial PR protein from Day 10 to Day 18 was similar to that
      in cyclic gilts. Western blot analysis with antiserum specific for the A and B
      isoforms of PR indicated that porcine endometrium expresses both isoforms of PR.
      Immunostaining was detectable for both the A and B isoforms of PR from Day 0 to
      Day 12 of the oestrous cycle. However, no staining was observed on Day 15 and Day
      18 of the oestrous cycle or pregnancy Immunocytochemical localization of PR in
      the endometrium of cyclic gilts and pregnant gilts indicated that there was
      intense staining for PR in surface epithelium and glandular epithelium during
      oestrus (Day 0) and on Day 5. However, the staining was less intense on Day 7 and
      Day 10 of the oestrous cycle and no epithelial staining was observed after Day
      12. PRs were present in the stroma and myometrium throughout the oestrous cycle
      and early pregnancy. The presence of conceptuses during pregnancy did not affect
      the loss of PR from the uterine epithelium after Day 10 of gestation. Down
      regulation of epithelial PR might be one factor involved in the timing of
      luteolysis during the oestrous cycle as well as conceptus growth and placentation
      during early pregnancy.

PMID- 7624518
TI  - Removal of the zona pellucida and parthenogenetic activation affect rates of
      survival of ultrarapidly frozen mouse oocytes.
AB  - Survival rates on thawing were assessed for ultrarapidly frozen mouse oocytes
      following the removal of zonae pellucidae using an acid Tyrode's solution,
      pronase or a mechanical dissection technique. Significantly higher rates of
      survival were observed for zona-free oocytes than for zona-intact control oocytes
      (303/684, 44% v. 130/498, 26%; P < 0.001). The rates of survival observed for
      pronuclear stage embryos (72-76%) were much greater than those observed for
      oocytes and were not influenced by zona removal techniques. Parthenogenetic
      activation of oocytes by exposure to a 7% (v/v) ethanol solution was also shown
      to increase survival rates of ultrarapidly frozen oocytes (155/185, 84% v.
      19/102, 19%) indicating that fusion of sperm to the plasma membrane or formation
      of a male pronucleus are not directly responsible for the increased survival
      rates of pronuclear stage embryos compared with oocytes. These data support the
      hypothesis that increased survival of ultrarapidly frozen pronuclear stage
      embryos is the result of changes to the plasma membrane and/or to the zona
      pellucida that occur following fertilization.

PMID- 7624517
TI  - Cloning and characterization of a fox sperm protein FSA-1.
AB  - A monoclonal antibody was raised to a fox sperm protein (FSA-1) which was found
      to be localized to the inner acrosomal compartment of sperm fixed in methanol.
      Western blots of testicular germ cell membrane extracts probed with this antibody
      identified a major protein band with a molecular weight of 36,000.
      Immunofluorescent studies on fox testis sections showed that the antigen is
      expressed on round and elongating spermatids on a crescent-shaped structure,
      which probably represents the developing acrosome. An antibody specific for FSA-1
      was used to screen a fox testis cDNA library for its cognate gene. An 875-bp cDNA
      clone was isolated and sequenced revealing an open reading frame. Searches of the
      GenBank and EMBL databases with the nucleic acid sequence revealed significant
      homology (86%) of FSA-1 with 406 bases of an unidentified RNA transcript from
      human fetal brain (EST02625). Northern blot analysis of fox testis RNA samples
      identified an RNA transcript of approximately 0.9 kb during the months when
      spermatogenesis is active. Zoo Northern blots (at high stringency) reveal an RNA
      transcript of a similar size present in testis RNA from dogs and mice. Zoo
      Southern analysis (high stringency) reveal genomic sequences present in dogs,
      mice, cattle and sheep. At present, the function of the FSA-1 gene product
      remains unknown, but it may play a role as a structural protein component of the
      acrosome.

PMID- 7624519
TI  - Comparisons between peripheral progesterone concentrations in cyclic and pregnant
      Landrace x large White and Meishan gilts.
AB  - Progesterone concentrations were determined in blood samples collected twice
      daily (at 0900 and 1700 hours) from the day of oestrus (Day 0) until Days 15-24
      in ten Landrace x Large White gilts (four cyclic and six pregnant gilts) and
      eight Meishan gilts (four cyclic and four pregnant gilts). Progesterone
      concentrations during the early luteal phase tended to be higher in pregnant
      Meishan gilts than in pregnant Landrace x Large White gilts. Furthermore, when
      differences in ovulation rate and peak progesterone concentrations were accounted
      for, maximum progesterone concentrations occurred earlier in Meishan gilts than
      in Landrace x Large White gilts (P < 0.01); this difference was particularly
      marked when pregnant animals of the two breeds were compared. In non-mated
      animals, analyses of the timing and magnitude of progesterone concentrations
      observed towards the end of the oestrous cycle revealed that the decrease in
      progesterone concentrations occurred earlier (P < 0.05) in Meishan gilts. Such
      breed differences in the peripheral progesterone profile may be associated with
      reduced prenatal mortality, a characteristic of Meishan females.

PMID- 7624520
TI  - Intrauterine and peripheral steroid concentrations and conceptus development in
      Meishan and Large White hybrid gilts.
AB  - Six Meishan and five Large White hybrid gilts were naturally mated to boars of
      the same breed during their tenth or third oestrous cycle respectively. Maternal
      serum progesterone and total oestrone were monitored throughout the pregnancy
      period. On Day 30 of gestation, all gilts were slaughtered and ovulation rate,
      embryonic survival, conceptus development and intrauterine steroidogenesis were
      evaluated. The results of the study confirm previous reports that Meishan pigs
      have a higher number of live conceptuses (P < 0.03), a higher rate of embryonic
      survival (92.1% v. 78.6% for Large White hybrids) and a higher ovulation rate (P
      < 0.02) than Large White hybrid gilts. Embryos from Large White hybrid gilts were
      heavier (P < 0.001) than Meishan embryos and placental lengths (P < 0.001) and
      weights (P < 0.001) were greater. The volume of allantoic fluid per conceptus was
      greater (P < 0.03) in Large White hybrid gilts. The oestradiol concentration in
      the allantoic fluid was greater in Large White hybrid gilts (P < 0.002), but the
      progesterone concentration in allantoic fluid did not differ (P > 0.15) between
      the breeds. More oestradiol was synthesized in vitro on a wet weight basis from
      placental tissue in Large White hybrid gilts than in Meishan gilts (P < 0.001);
      however, a positive linear relationship existed in both breeds between oestradiol
      synthesis and placental length (P < 0.005). Progesterone concentrations in
      maternal serum tended to be higher overall (P < 0.1) in Meishan gilts than in
      Large White hybrid gilts throughout the 30-day period of study and were
      significantly higher (P < 0.02) from Day 13 to Day 30.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7624521
TI  - The proopiomelanocortin gene is expressed as both full-length and 5'truncated
      transcripts in rodent Leydig cells.
AB  - A reverse transcription polymerase chain reaction (RT-PCR) assay was developed to
      distinguish between full-length transcripts and functionally aberrant, truncated
      transcripts of the proopiomelanocortin (POMC) gene. This assay was applied to RNA
      obtained from the testes of rats and mice, to Percoll-purified primary mouse
      Leydig cells, and to various Leydig-derived cell lines. The results indicate a
      very low level of expression for the full-length transcripts in whole rodent
      testis, in mouse Leydig cells and in the MA10 cell line. In Leydig cells, the
      major transcripts of the POMC gene were the shorter, truncated transcripts where
      the regions corresponding to exons 1 and 2 are missing.

PMID- 7624522
TI  - Icons and the perpetuation of error.

PMID- 7624524
TI  - Personality, appraisal, and adaptational outcomes in HIV seropositive men and
      women.
AB  - A cross-sectional exploratory design was used to assess the relationships of
      personality, socioeconomic status, and appraisal with functional and emotional
      outcomes in 77 men and 50 women with HIV infection. Multiple regression analysis
      showed that, among men, socioeconomic status moderated the negative relationship
      between self-esteem and disruption in usual activities. Consistent with Lazarus
      and Folkman's (1984) theory, appraisal of HIV threat mediated the negative
      relationship between self-esteem and mood disturbance for men and women, and the
      positive relationship between self-esteem and purpose in life for women.
      Appraisal did not mediate between personality variables and disruption in usual
      activities or life satisfaction for men or women.

PMID- 7624523
TI  - Service use by elders with heart disease.
AB  - The study purpose was to determine the impact of demographic, social,
      environmental, and health indicators on utilization of health services among
      elders with heart disease. Existing data from a regional Area Agency on Aging
      were used and the sample (N = 1,167) included vulnerable groups, men, blacks, low
      income, and rural residents. Services most frequently used were case management,
      congregate meal, home delivered meal, outreach, and recreation. Multiple linear
      and logistic regression indicated that race, marital status, living arrangements,
      payment source, residence, transportation capability, health conditions, sensory
      impairment, and function were predictors of service use.

PMID- 7624525
TI  - Gender and knowledge about HIV, risky sexual behavior, and safer sex practices.
AB  - The purpose of this study was to examine gender differences in knowledge about
      HIV, the reported incidence of risky sexual behavior, and comfort with safer
      sexual practices among young adults. The conceptual framework was social role
      theory, which argues for the influence of gender roles on beliefs and social
      behaviors. Participants were 141 female and 131 male college students who
      responded to questions regarding their knowledge of HIV, risk-taking behaviors
      with respect to HIV, and comfort with safer sexual behaviors. Overall,
      respondents had accurate knowledge about HIV. However, men reported engaging in
      significantly more risky behaviors than women. More men reported that intercourse
      without a condom occurred in unplanned, spontaneous situations, while under the
      influence of alcohol or drugs, or with a person not well known. More women
      reported that intercourse without a condom occurred in long-term relationships.
      Women were significantly more comfortable abstaining from sexual intercourse and
      asking partners about their sexual history while men were significantly more
      comfortable buying condoms. Both men and women reported comfort using condoms.
      Gender roles help to explain why men are willing to take more risks, and in what
      situations risk taking is apt to occur.

PMID- 7624526
TI  - Sources of social support and conflict in hospitalized depressed women.
AB  - The purpose of this study was to (a) describe the number and types of social
      relationships of 39 women hospitalized for unipolar depression and (b) examine
      differences in the provision of social support and level of conflict among these
      types of relationships. Paired t tests were used to compare support and conflict
      from six types of relationships. The number and range of relationships reported
      were comparable to those of nondepressed women. Unexpectedly, women reported low
      amounts of conflict. Spouse/partners, household, and close relationships were
      perceived as sources of the most support. However, spouse/partner and household
      members also provided the most conflict, while close relationships provided the
      least. These close relationships play a pivotal role in the provision of social
      support. Furthermore, close female relationships appear to provide the benefits
      of support without the cost of conflict.

PMID- 7624527
TI  - Experienced and inexperienced mothers' maternal competence during infancy.
AB  - In an exploratory study 136 experienced (multiparous) mothers and 166
      inexperienced (primiparous) mothers were studied to determine differences in
      their self-reported maternal role competence, and variables predicting their
      competence at postpartal hospitalization, 1, 4, and 8 months following birth. The
      two groups did not differ in their maternal role competence over the 8 months.
      Inexperienced mothers' competence was higher at 4 and 8 months than at early
      postpartum and 1 month, indicating a developmental process in maternal role
      achievement, but no change was observed in experienced mothers' maternal
      competence. From 45% to 56% of the variance in experienced mothers' maternal
      competence was explained over the four test periods, and from 43% to 50% among
      inexperienced mothers. Self-esteem was a consistent, major predictor of maternal
      competence for both groups. Maternal fetal attachment, readiness for pregnancy,
      and pregnancy risk variables were explanatory of experienced mothers' maternal
      competence only. Sense of control was explanatory only of inexperienced mothers'
      competence at 1, 4, and 8 months.

PMID- 7624528
TI  - Intensive care decisions about level of aggressiveness of care.
AB  - Questionnaires were used to assess (a) the factors intensive care unit resident
      physicians (N = 33) and nurses (N = 57) perceived as influential in making
      decisions about level of aggressiveness of patient care (LAC), (b) who residents
      and nurses believed should be involved versus who was involved in decision
      making, and (c) the amount of collaboration they perceived in their practices.
      Questionnaires then were used to assess decision making about 314 patients. All
      providers agreed that patient request influenced their LAC decisions, with
      possibility of benefit and diagnosis ranked second and third. Although both
      nurses and residents believed capable patients should be making LAC decisions,
      providers identified attending physicians as the most common participants in
      decision making for specific patients. Residents were more satisfied with the
      decision making process than nurses, t = 2.05 (88), p = .04. There was no
      relationship between perceptions of nurse-resident collaboration and providers'
      inclusion of others in the LAC decision process.

PMID- 7624529
TI  - The effect of caloric density of food on energy intake and body weight in tumor
      bearing rats.
AB  - Anorexia and weight loss are major problems for cancer patients and are
      associated with increased cancer morbidity and mortality. The current clinical
      approach is to encourage high calorie food intake. In the present study, we used
      an animal model of tumor-induced anorexia to evaluate the effect of feeding a
      high caloric diet on food and caloric intake and body weight of tumor-bearing
      rats. Tumor-bearing rats fed a diet containing 4.7 kcal/g reduced the amount of
      food they ate to equal the caloric intake of rats fed a diet containing 3.7
      kcal/g. Body weight and tumor growth were not affected by the diet intervention.
      These data suggest that energy intake is regulated in tumor-bearing rats as it is
      in healthy animals, albeit at a lower level. These data have implications for
      further study of the effects of nutritional supplements on food intake and
      nutritional status of cancer patients.

PMID- 7624530
TI  - Agreement between measures of pulmonary artery and tympanic temperatures.
AB  - The purposes of this study were to compare pulmonary artery, oral, axillary, and
      two tympanic temperatures and test agreement between measures of pulmonary artery
      and tympanic temperatures in a convenience sample of 32 Intensive Care Unit
      patients. The correlation coefficients for pulmonary artery and oral, axillary,
      and tympanic temperatures were moderate to strong and significant at the p < .01
      level. However, intraclass correlation coefficients estimated the intermethod
      reliability and were below the .75 criterion of acceptability. Thus, one method
      of temperature measurement could not be interchanged for another.

PMID- 7624531
TI  - Qualitative analysis: what it is and how to begin.
AB  - One of the most paralyzing moments in conducting qualitative research is
      beginning analysis, when researchers must first look at their data in order to
      see what they should look for in their data. Although temporally and conceptually
      overlapping processes, data analysis should be distinguished from interpretation.
      Practical suggestions for beginning analysis include getting a sense of the
      whole, extracting the facts, identifying key topics or major storylines and
      dimensionalizing their informational content, and using frameworks to reduce
      data.

PMID- 7624532
TI  - . . . more on therapeutic touch.

PMID- 7624535
TI  - . . . more on therapeutic touch.

PMID- 7624534
TI  - . . . more on therapeutic touch.

PMID- 7624533
TI  - Theory in nursing research.

PMID- 7624536
TI  - . . . more on therapeutic touch.

PMID- 7624537
TI  - Women, alcohol, and driving.
AB  - Alcohol-related crashes and fatalities have shown a dramatic decrease over the
      last decade. While males continue to account for most alcohol-related crashes,
      females are an increasing proportion of alcohol-involved drivers in both fatal
      and nonfatal crashes. Although most research has not addressed the possibility of
      gender differences in the effects of alcohol on driving performance, available
      evidence suggests that such differences may exist. Alcohol appears to have
      greater effects on females in terms of biomedical damage and impaired
      performance, although these effects have not been systematically investigated in
      relation to driving. Effective prevention programs for women require more focused
      research to understand gender-related factors in the effects of alcohol on
      driving.

PMID- 7624538
TI  - Employed women with alcohol problems who seek help from employee assistance
      programs. Description and comparisons.
AB  - After a brief description of employee assistance programs (EAP), we present data
      collected from 6,400 employees from 84 worksites who used the services of EAPs, a
      portion of whom were assessed by the EAP as having alcohol-related problems
      and/or received scores on the Alcohol Dependence Scale (ADS) indicative of a
      potential alcohol-related problem. In addition, data were collected at intake
      from the EAP administrators, and employment status of the employee clients was
      assessed 18 to 24 months later. These data indicate that EAPs are effective in
      sustaining the employment of most women with alcohol-related problems who seek
      services from EAPs and that EAPs' goal of early intervention is especially
      realized among women with alcohol problems. Other conclusions include: women with
      alcohol problems do not enter EAPs through routes that are strikingly different
      from those of men; many of the gender differences that are revealed are
      associated with job status differences; employed women with alcohol problems are
      detached from nuclear families, with markedly low rates of current marriage; even
      when married, spouses are less likely to play a role in the referral of women
      with alcohol problems than the spouses of the men; and, there is no clear
      indication that women are the target of any form of discrimination in the process
      of EAP utilization. However, women are considerably more likely to have less
      adequate insurance coverage, according to the EAP administrators' assessment
      reported at client intake, than their male counterparts, leading to treatment
      choices that may be less than appropriate.

PMID- 7624539
TI  - Gender differences in alcohol metabolism. Physiological responses to ethanol.
AB  - A gender difference in alcohol pharmacokinetics has been suggested to explain why
      women are more vulnerable to ethanol's toxic effects. The results of animal
      experiments suggest that females exhibit higher alcohol metabolic rates than
      males as a result of hormonal differences. Experimental results examining gender
      differences in human alcohol metabolism have been inconsistent; the diversity of
      experimental protocols and variety of pharmacokinetic parameters reported have
      made comparisons of these studies very difficult. Variability in alcohol
      metabolic rate between individuals of the same sex is often significant,
      preventing an assessment of gender differences in some studies. This chapter
      attempts to summarize the findings of studies from the last decade that examined
      the role of gender and sex hormone differences on ethanol metabolism in men and
      women. The role of body composition, genetic factors, gastric and hepatic alcohol
      dehydrogenase, and gastric absorption in creating gender differences in alcohol
      metabolism is discussed. Suggestions are offered that may result in better cross
      study comparisons and more consistent experimental results.

PMID- 7624540
TI  - Mental and physical health consequences of alcohol use in women.
AB  - Chronic consumption of alcohol in levels typically consumed by alcoholic women
      clearly produces adverse health consequences, including a shorter life
      expectancy. The health consequences of alcohol use appear to depend on the
      characteristics of the person consuming the alcohol (genetic vulnerability to
      particular diseases, the particular point in the life span when the majority of
      the alcohol is consumed, and the pattern of consumption typical for that
      individual). For adolescence and young adulthood, emphasis is placed on increased
      rates of accidental and suicidal mortality. For middle age, breast cancer risk
      and risk for developing osteoporosis is discussed. Finally, use of alcohol alone
      and in combination with psychoactive drugs presents special problems for older
      women. Other specific adverse effects of alcohol are reviewed with respect to
      gender differences in cardiovascular, hepatological, and neuropathological
      outcome, as well as with respect to HIV/AIDS. Psychiatric comorbidity and
      domestic violence are also discussed with respect to gender differences.

PMID- 7624541
TI  - Alcohol effects on hormone levels in normal postmenopausal women and in
      postmenopausal women with alcohol-induced cirrhosis.
AB  - The effects of alcoholic beverage consumption on the hormonal status of
      postmenopausal women will be reviewed. Focused attention on the effect of social
      drinking 244 normal postmenopausal women has revealed that moderate alcohol
      intake exerts a major influence not only on estradiol, testosterone, and the
      estimate of aromatization of testosterone to estradiol but also on the estrogen
      responsive pituitary hormones in normal postmenopausal women. The hormonal status
      of 66 postmenopausal women with alcohol-induced cirrhosis is compared with normal
      alcohol-abstaining control women. As expected, there are significant differences
      in levels of all hormones; furthermore, hormonal interrelationships are also
      disrupted. Of major interest are findings that hormone levels in alcoholic
      cirrhotic postmenopausal women are related to the severity of liver disease. This
      observation supports a role for cirrhosis per se in the hormonal disruptions
      noted. Of further interest are findings that hormone levels may have prognostic
      value in postmenopausal women with alcohol-induced liver disease.

PMID- 7624542
TI  - Gender differences in animal studies. Implications for the study of human
      alcoholism.
AB  - The reasons for gender differences in alcohol intake, responses to alcohol, and
      consequences of alcohol abuse in humans and in animals are poorly understood.
      Animal models for the study of alcoholism have been focused primarily on the
      study of male rodents, although researchers have observed that female rodents
      drink more alcohol than males and have sex-related differences in drinking
      patterns and responses to alcohol. In humans, the difference between the sexes is
      the opposite of rodents, with males drinking more than females. These results
      suggest differences between the sexes and differences between humans and rodents
      in drinking behavior and responses to alcohol which may be based on a complex
      interaction of social, genetic, hormonal, neurobiologic, and environmental
      factors. Four new studies are introduced to identify sex-distinct genetic
      influences in alcohol-related phenotypes, sex-based differences in behavioral
      responses to alcohol, sex differences in responses of brain reward systems to
      alcohol, and interactions of the anxiolytic effects of alcohol with steroids and
      the estrous cycle.

PMID- 7624543
TI  - Sex distinctiveness in effective genotype.
AB  - The difference between sexes in incidence and prevalence of alcohol-related
      problems is a central feature of alcohol research. It is inevitable that these
      differences will receive escalating attention as it becomes increasingly apparent
      that the interests of both equity and good science are served by the study of sex
      differences in health-related processes. For several reasons, genetic methods
      promise to offer powerful tools for the elucidation of sex differences. In the
      first place, the determination of sex depends on a genetic mechanism.
      Furthermore, there is an abundant literature showing the relevance of heredity to
      a broad variety of alcohol-related processes. Moreover, there is evidence of
      major differences in genetic influences in males and females in respect to
      alcoholism specifically. It is important to appreciate that genetic influence on
      sex distinctiveness may operate through several different mechanisms, with quite
      different implications. The purpose of this chapter is to provide an elementary
      description of these different genetic routes to sex differences.

PMID- 7624544
TI  - Sex differences in ethanol-related behaviors in genetically defined murine
      stocks.
AB  - Over the past 30 years, there have been a number of important developments in our
      understanding of the etiology and consequences of excessive drinking among
      humans. Probably one of the most important findings to date is that there are
      large individual differences among humans in appetite for alcohol and age of
      onset of problem drinking. We recognize this finding in at least two different
      alcoholic types, each with its own estimate of genetic influence. We have also
      come to realize that there are important differences between men and women, both
      in etiology of problem drinking and in the consequences of chronic alcohol use.
      In this chapter, the advantages and limitations of applying genetically defined
      animal models, primarily, selected lines and inbred strains of mice, are
      evaluated with examples from the literature.

PMID- 7624545
TI  - Sex differences in mesolimbic dopamine responses to ethanol and relationship to
      ethanol intake in rats.
AB  - Sex differences in ethanol intake in rats suggest that there may be sex
      differences in brain dopamine systems believed to mediate ethanol's reinforcing
      properties. To test this hypothesis, we used in vivo microdialysis to examine
      changes in nucleus accumbens and striatal dopamine, DOPAC and HVA following acute
      administration of several doses of ethanol in male and female Long-Evans rats.
      Following dialysis, rats were trained to bar press for oral ethanol
      reinforcement. In nucleus accumbens, females showed greater increases in dopamine
      than males at low to intermediate doses. In striatum, both sexes showed increased
      dopamine at the low to intermediate doses. In addition to showing increased
      responsiveness to ethanol-induced mesolimbic dopamine stimulation, females
      consumed more ethanol than males during behavioral testing. Correlations between
      neurochemical measures and subsequent ethanol consumption indicated that among
      males, both basal and peak ethanol-induced nucleus accumbens dopamine levels were
      inversely related to later ethanol intake. No such relationship was observed for
      females. Striatal neurochemical measures were not significantly related to
      ethanol intake. These findings supported the hypothesis of sex differences in
      mesolimbic responses to ethanol and suggested that the relationship of those
      responses to subsequent ethanol intake may differ for males and females.

PMID- 7624546
TI  - Anxiolytic effects of steroid hormones during the estrous cycle. Interactions
      with ethanol.
AB  - Behavioral differences in anxiety have been observed between both males and
      females and across the ovarian cycle in females. However, the data are not
      entirely consistent and the mechanisms of this potential interaction are largely
      unexplored. It appears that the GABA/BZ receptor complex is a site of action for
      steroids as well as for many anxiolytic drugs. Both natural steroids, such as
      progesterone and its metabolites, and synthetic steroids, such as alphaxalone,
      reduce anxiety-like behavior in rats. Alphaxolone also reverses the behavioral
      effects of potent anxiogenic agents in the conflict test of anxiety. Studies
      reported here found that ethanol administered to rats in different phases of the
      estrous cycle was more effective as an anxiolytic when hormone levels were high.
      The anticonflict response to chlordiazepoxide also was examined in ovariectomized
      and steroid-replaced female rats. Insight into the mechanisms and sites of action
      for these steroids can be gained from such an approach.

PMID- 7624547
TI  - Women, alcohol, and sexuality.
AB  - Alcohol consumption increases subjective sexual desire, arousal, and pleasure for
      many women, although it lowers physiological arousal. Despite the general belief
      that alcohol disinhibits female sexual behaviors, alcohol leads to changes in
      sexual behavior only for a minority of women. Expectancies about the effects of
      alcohol on sexual behavior may be important mediators of the alcohol-sexual
      behavior linkage. There also is a relationship between overall alcohol
      consumption and risky sexual behavior for women, but when alcohol use at or
      preceding individual instances of sexual activity is examined, there is no
      association in the majority of studies. Alcohol use by both perpetrators and
      victims has been implicated in instances of sexual victimization. Heavy alcohol
      consumption and alcohol problems in women are associated with heightened risk of
      childhood incest, sexual assault, and sexual dysfunction.

PMID- 7624548
TI  - Cognitive psychosocial performance and recovery in female alcoholics.
AB  - Female alcoholics experience greater affective symptomatology and are more
      frequently labeled with comorbid psychiatric diagnoses than male alcoholics.
      Subgroups of male and female alcoholics with antisocial symptomatology are
      strikingly similar across behavioral, psychosocial, and alcohol and drug use
      variables. Relative to controls, female alcoholics manifest deficits in standard
      neuropsychological testing as well as efficiency of information processing,
      interpersonal problem solving, neurophysiological measures, and
      neurophysiological assessment. The deficits are quite similar to those of male
      alcoholics. However, females may manifest a differential susceptibility to
      alcohol given the females' comparatively shorter drinking careers. There are no
      overall sex differences in relapse rates following treatment, although various
      personal and environmental factors play gender-specific roles in outcome.
      Patterns of recovery function with abstinence are similar for male and female
      alcoholics.

PMID- 7624549
TI  - Drinking and problem drinking in US women. Patterns and recent trends.
AB  - General population surveys suggest that the percentage of US women who drink
      declined slightly during the 1980s. Comparisons of 1981 and 1991 national surveys
      using the same drinking measures show that fewer women drank heavily in 1991, and
      women drinkers drank less frequently and had fewer episodes of heavy drinking,
      although younger drinkers reported more frequent intoxication. Longitudinal
      analyses of 5-year changes in drinking behavior indicate that movement both into
      and out of problem drinking is greatest among women aged 21 to 34. Subgroups of
      women with elevated rates of heavy drinking and/or adverse drinking consequences
      include younger women; women lacking social roles or occupying unwanted social
      statuses; women in nontraditional jobs; cohabiting women; and ethnic minority
      women experiencing rapid acculturation. Risks of heavy and/or problem drinking
      are also greater among women with a heavy-drinking husband or partner;
      depression; sexual dysfunction; or violent victimization in childhood or
      adulthood. Future research should focus on (1) the causes and consequences of
      recent declines in women's drinking; (2) antecedents and consequences of specific
      patterns of multiple substance use in women; (3) social and relational contexts
      of women's drinking, including occupational influences, drinking behavior of
      significant others, sexual dysfunction, and relationship violence; (4)
      longitudinal predictors of both problem drinking onset and "spontaneous"
      remission of women's alcohol problems; and (5) childhood sexual abuse as a
      potentially powerful risk factor for later alcohol abuse in women.

PMID- 7624550
TI  - Epidemiology. Introduction.

PMID- 7624551
TI  - The emergence of problem-drinking women as a special population in need of
      treatment.
AB  - This chapter chronicles the development of advocacy for improvements in alcohol
      treatment services for women during the 1970s and 1980s, tracing its influence in
      terms of real change in treatment systems in the United States. We follow the
      development of a "women's alcoholism movement" from its inception in the late
      1970s through its transition during the late 1980s into a broader movement
      focused on drug abuse and perinatal addiction. We describe the new governing
      images of problem-drinking women that advocates presented, their claims about the
      nature of substance abuse problems in women, and their recommendations for a more
      "gender-sensitive" treatment system. We also review increased federal involvement
      in this issue over the course of the 1980s, as pressure mounted on policymakers
      to respond to the crisis over drug-exposed infants by making treatment services
      more accessible to women. The chapter concludes by considering these developments
      from the perspective of national treatment system statistics, finding modest
      growth in specialized and women-only treatment units, as well as moderate
      increases in the representation of women in substance abuse treatment caseloads.

PMID- 7624552
TI  - Race/ethnicity and other sociocultural influences on alcoholism treatment for
      women.
AB  - This chapter discusses sociocultural influences on the availability, access,
      diagnosis, and treatment of alcoholism for women, particularly those in minority
      groups. Race/ethnicity and other sociocultural influences are presented in terms
      of the societal context and the counselor-client relationship. The latest data on
      heavy drinking, alcohol-induced mortality, and alcoholism treatment utilization
      are presented on African-American, Hispanic, and white women. Data also are
      presented on the ability to pay for treatment through insurance or earnings.
      Information on Native Americans and Asian/Pacific Islanders is included whenever
      possible.

PMID- 7624553
TI  - Patterns of alcohol use among ethnic minority adolescent women.
AB  - There is agreement in the literature that women of the major ethnic groups in the
      United States have lower rates of alcohol use and suffer fewer alcohol-related
      problems than men. In adolescence, the highest rates of alcohol use are generally
      found among American Indians, followed in decreasing order by whites, Hispanics,
      African-Americans, and Asian-Americans. The role of sociocultural factors in
      alcohol use as found in the literature is discussed, including level of
      acculturation, generational status, culturally specific values and beliefs and
      peer influence. Lifetime and last 30-day prevalence, age of first time drunk, and
      peer sanction data from the 1989-93 database of The American Drug and Alcohol
      Survey are presented by gender and ethnicity for 8th and 12th graders. These data
      show similar rates of alcohol use by males and females in the 8th grade but more
      use by males in the 12th grade for all ethnicities except American Indians who
      live on reservations.

PMID- 7624554
TI  - Alcoholism in the family. A multicultural exploration.
AB  - The initial focus is on defining race, culture, and ethnicity, followed by a
      review of the extent of alcohol and alcohol use consequences among African
      Americans and Native Americans. Cultural specificity in an historical context is
      provided. A brief overview of gaps in the incident and prevalence data is
      presented. The biosociocultural context of drinking among African-American women
      with specific emphasis on cultural disruption, socialization, and social class is
      explored. A triracial infant girl (African-American/Native American/German-Irish
      American), whose family genogram documents, by the case study method, six
      generations back to slavery, is presented. The alcohol use patterns within this
      family are somewhat illustrative of historical patterns and of racial and ethnic
      import. An absence of religiosity/spirituality is noted. The family genogram is
      followed by a discussion of the limitations of the case study method of family
      genograms. The final section relates the findings of the family genogram back to
      the extant data and the gaps in the collection of data regarding the epidemiology
      of alcoholism across groups. It highlights the recent findings and questions
      raised by those findings from cross-cultural and racial studies of alcoholism
      among women of color.

PMID- 7624555
TI  - Gender differences for the risk of alcohol-related problems in multiple national
      contexts.
AB  - The primary research question asked is: After holding alcohol consumption
      constant, will men and women be at equal risk for a variety of alcohol-related
      problems? Since women are actually at a higher blood alcohol content at the same
      consumption levels, a physiological argument would suggest that women are at
      equal or greater risk for alcohol problems than men. However, variation in
      societal norms surrounding gender roles and/or societal-level stress may mediate
      the experience of men and women, regardless of the differences in physiology. Ten
      cross-sectional general population studies are used. Analyses control for
      individual-level variables (age, quantity, and frequency of drinking) and
      societal-level variables (proportion of women in the work force and female
      suicide rate) that might confound these relationships; cross-study homogeneity is
      examined.

PMID- 7624556
TI  - Older women and alcohol. Use and abuse.
AB  - Although estimates of elderly problem drinkers and alcohol-related health
      problems among the elderly are approximate, there does appear to be a decline in
      the number of drinkers and the number of heavy drinkers. As with all age groups,
      there are fewer women who drink than men and fewer women problem drinkers.
      Moderate social drinking varies with health and income. Among older women, there
      may well be more problematic use of prescribed psychoactive drugs than alcohol.
      In the few studies of older problem drinkers available, there are gender
      differences: Older men are more likely to be married, divorced, or separated, but
      older women problem drinkers show a hgh rate of widowhood; onset is more recent
      for older women than for older men; older women are more problematic users of
      prescribed psychoactive drugs; and the prevailing comorbidity among older women
      alcohol abusers is probably depressive disorder.

PMID- 7624557
TI  - Violent victimization among women with alcohol problems.
AB  - Empirical evidence regarding the role of childhood victimization in the
      development of women's alcohol problems is examined in this chapter. In
      particular, childhood sexual abuse and father-to-daughter violence are found to
      predict later alcohol problems. Key variables that link experiences of childhood
      victimization and the development of adult alcohol problems are identified.
      Strengths and weaknesses of the research provide a better assessment of our
      confidence in the empirical evidence to date. Possible explanations for how and
      why the experiences of violent victimization may lead to women's alcohol problems
      are presented. Finally, important directions for policymakers, clinicians, and
      researchers are discussed.

PMID- 7624558
TI  - Vulnerability to alcoholism in women. Genetic and cultural factors.
AB  - The etiology of alcoholism in women is no longer a question of nature or nurture.
      Most observers would agree that alcoholism, both male and female, is mediated by
      genetic factors. The question is how much of the variance is explained by genetic
      factors and to what degree is this genetically mediated disorder moderated by
      personal characteristics of the woman. Among the most salient personal
      characteristics moderating the genetic vulnerability may be factors such as age,
      ethnicity, and presence of psychiatric comorbidity. Cultural factors and familial
      environmental factors are most likely predictors as well. Therefore, the chapter
      will discuss the genetic epidemiology of alcoholism in women. Genetic
      heterogeneity will be discussed and evidence presented that suggests the
      existence of two forms of alcoholism in women: one more environmentally
      determined and one more influenced by genetic mediation. Evidence for the
      existence of a genetic diathesis in women will be presented, noting extant
      literature involving twin and adoption designs. Suggestions for what might be
      transmitted from generation to generation (e.g., neurobiological factors,
      temperament) with special reference to preadolescent and adolescent girls will
      also be discussed.

PMID- 7624559
TI  - Sonohysterography: a technique for endometrial evaluation.
AB  - Sonohysterography involves the instillation of sterile saline under continuous
      sonographic visualization to assess the endometrial cavity. The technique is most
      useful for evaluating women with fertility problems, postmenopausal bleeding, or
      an abnormal endometrial interface as seen at baseline sonography. The procedure
      is performed with saline instilled into the endometrial cavity through a 5-F
      pediatric feeding tube or a hysterosalpingography or insemination catheter. In
      the normal uterus, the endometrium appears symmetric, surrounding the anechoic,
      saline-distended endometrial cavity. Adhesions appear as bridging bands of tissue
      that distort the uterine cavity or as very thin, undulating membranes, best seen
      at real-time examination. An intracavitary polyp is seen surrounded by anechoic
      fluid, with the point of attachment and thickness of the stalk clearly
      demonstrated. The location of leiomyomas can be determined: Intramural lesions do
      not distort the endometrial cavity, whereas submucosal lesions often do, with the
      overlying normal layer of endometrium clearly seen. In women with abnormal
      bleeding, focal areas of asymmetric endometrial thickening can be identified.
      Sonohysterography allows differentiation of intracavitary, endometrial, and
      submucosal abnormalities without the use of ionizing radiation or contrast
      agents.

PMID- 7624560
TI  - Prenatal detection of anterior abdominal wall defects with US.
AB  - The size and position of an anterior abdominal wall defect, its contents, and its
      association with other anomalies are features that can be diagnosed in utero with
      ultrasound and that allow a differential diagnosis to be made. The correct
      prenatal diagnosis is extremely important for patient management. The key feature
      for sonographically distinguishing these conditions is the position of the defect
      in relation to the umbilical cord insertion. Omphaloceles and pentalogy of
      Cantrell usually involve a midline defect at the umbilical cord insertion.
      Gastroschisis most frequently consists of a small, right-sided paraumbilical
      defect. Eccentric, large lateral defects are typically present in limb-body wall
      complex or amniotic band syndrome. Bladder and cloacal exstrophy involve the
      infraumbilical region. In addition, the size of the defect, the organs
      eviscerated, the presence of membranes or bands, and any associated abnormalities
      help determine the correct diagnosis. Increased knowledge of these uncommon fetal
      conditions should result in better detection, more accurate diagnosis, and
      improved management of anterior abdominal wall defects.

PMID- 7624561
TI  - CT and MR imaging of the buccal space and buccal space masses.
AB  - The authors describe the normal variations in the buccal space and present the
      range of buccal space pathologic conditions seen on computed tomographic (CT) and
      magnetic resonance (MR) images. In a series of 50 patients studied with CT and 30
      with MR imaging, the visualization and measurement of the normal facial
      expression and buccinator muscles, parotidomasseteric fascia, parotid duct,
      accessory parotid tissue, and facial neurovascular bundle were statistically
      equivalent. The size of the buccal fat pad was statistically the same from side
      to side within a given patient. Normal lymph nodes were rarely discernible from
      the facial neurovascular bundles. In a series of 26 patients with unsuspected
      buccal space masses, salivary gland tumors were the most common masses. Less
      frequently, benign lesions (eg, hemangioma and dilated parotid ducts) and soft
      tissue malignancies (eg, sarcoma) manifested as buccal space masses.
      Occasionally, a cheek mass of uncertain cause proved to be lymphadenopathy;
      however, adenopathy is more commonly associated with clinically evident, deeply
      infiltrating facial neoplasms. Knowledge of the anatomic variations and expected
      abnormalities of the buccal space is useful for the radiologist interpreting
      facial CT or MR images.

PMID- 7624562
TI  - MR imaging of the posterior cruciate ligament: normal, abnormal, and associated
      injury patterns.
AB  - The posterior cruciate ligament (PCL) of the knee has received little attention
      in the radiology literature, but its importance in knee stability has come under
      close scrutiny in recent years. Unrepaired injury of the PCL can lead to chronic
      instability and early joint degeneration. Three major mechanisms of trauma that
      involves the PCL are posterior displacement of the tibia in a flexed knee,
      hyperextension, and rotation combined with an adduction or abduction force. The
      spectrum of PCL injuries includes partial tear or intrasubstance injury, complete
      ligamentous rupture, and avulsion of the PCL insertion site on the posterior
      tibia. Associated injuries include injury of other ligaments, meniscal tear, bone
      injury, and joint effusion. PCL rupture is easily identified with magnetic
      resonance (MR) imaging by using simple signal intensity and structural
      characteristics. Because clinical and arthroscopic assessment of the PCL can be
      difficult, MR imaging can be valuable for evaluating the acutely injured knee
      when operative repair of the PCL is being considered.

PMID- 7624563
TI  - The idiopathic inflammatory myopathies: spectrum of MR imaging findings.
AB  - Magnetic resonance (MR) imaging is useful for demonstrating the soft-tissue and
      musculature changes seen in patients with idiopathic inflammatory myopathies
      (IIMs). These changes include edema within and around muscle, subcutaneous
      reticulation, muscle calcification, and fatty infiltration of muscle. Muscle
      edema is visible as areas of hyperintensity on short inversion time inversion
      recovery (STIR) images. Abnormal reticulation of the subcutaneous tissue can be
      due to subcutaneous edema or an infiltrating process; edema from inflammation
      appears as areas of low signal intensity on T1-weighted images and as areas of
      high signal intensity on STIR images. Intramuscular calcium deposition appears as
      hypointense areas with all pulse sequences. On T1-weighted images, fatty
      infiltration appears as areas of high signal intensity within muscles. Because of
      the improved visualization of muscle inflammation provided by STIR imaging and
      because MR imaging is noninvasive, it has become a useful modality for evaluating
      patients with IIMs.

PMID- 7624565
TI  - Color Doppler US of the orbit.
AB  - Color Doppler imaging of the orbit shows promise in evaluation of several types
      of orbital abnormalities. The most promising use is for evaluation of vascular
      disorders. Screening for orbital varices and cavernous-carotid fistulas is easily
      accomplished. Color Doppler imaging can also be useful in diagnosis of ocular
      ischemia, central retinal vessel occlusion, and anterior ischemic optic
      neuropathy. In cases of inflammatory disease, it may be helpful in searching for
      complications of infection and in monitoring the size of fluid collections. In
      cases of tumors, color Doppler imaging can be used to monitor lesion size and in
      surgical planning. More work needs to be done to determine the role of color
      Doppler imaging in evaluation of trauma and congenital abnormalities. An
      understanding of the basic anatomy of the orbit, examination techniques, and
      common disease processes in the orbit will allow the radiologist to offer this
      potentially valuable modality to referring clinicians.

PMID- 7624564
TI  - MR imaging of the major carpal stabilizing ligaments: normal anatomy and clinical
      examples.
AB  - The integrity of the ligamentous network of the wrist is critical, as disruption
      of this network may result in carpal instability and pain. The extrinsic
      (radiocarpal) and intrinsic (intercarpal) ligaments that maintain carpal
      stability can be evaluated with magnetic resonance (MR) imaging. The major
      extrinsic ligaments are the radioscaphocapitate, radiolunotriquetral, short
      radiolunate, and dorsal radiocarpal ligaments. The scapholunate and
      lunotriquetral ligaments are the most important intrinsic ligaments and the
      primary wrist stabilizers. The most common causes of carpal instability are
      unstable fracture of the scaphoid, scapholunate dissociation, and lunotriquetral
      dissociation. Carpal instability can be diagnosed from the sagittal MR image that
      includes the capitate, lunate, and radius and from the sagittal MR image that
      includes the scaphoid and radius. Knowledge of the MR imaging appearances of the
      major carpal stabilizing ligaments and common patterns of carpal instability
      allows more precise diagnosis in cases of wrist pain.

PMID- 7624566
TI  - Varices in portal hypertension: evaluation with CT.
AB  - The portosystemic collateral channels that can develop in portal hypertension are
      numerous, widespread, and varied in appearance. The reported prevalences of
      varices at each anatomic site vary according to the diagnostic modality used.
      Dynamic computed tomography (CT) performed with a bolus of contrast material
      demonstrates collateral vessels with exquisite detail. On CT scans, varices
      appear as well-defined found, tubular, or serpentine structures that are smooth,
      have homogeneous attenuation, and enhance with contrast material to the same
      degree as adjacent vessels. In 60 consecutive patients with varices and evidence
      of cirrhosis, the most common portosystemic collateral channels were coronary
      venous collateral vessels in the lesser omentum, seen in 80% of cases.
      Esophageal, paraumbilical, abdominal wall, perisplenic, retrogastric,
      paraesophageal, omental, retroperitoneal-paravertebral, and mesenteric varices
      were also found, along with spontaneous splenorenal and gastrorenal shunts.
      Knowledge of the CT appearance and the prevalence of varices at each anatomic
      site will improve diagnostic accuracy.

PMID- 7624567
TI  - Spiral CT during arterial portography: technique and applications.
AB  - Spiral computed tomography during arterial portography (CTAP) combines rapid
      scanning with selective imaging during the portal phase of enhancement of the
      liver, resulting in an effective method for evaluation of liver neoplasms prior
      to partial hepatic resection. Compared with dynamic incremental CTAP, spiral CTAP
      results in improved quality of three-dimensional and multiplanar reconstructions,
      facilitating presurgical planning. Accurate volumetric analysis of the tumor can
      be performed, and subsegmental tumor localization is facilitated by the high
      levels of hepatic and portal venous enhancement. Additional advantages of spiral
      CTAP include small reconstruction intervals for improved lesion detection.
      However, the specificity of spiral CTAP is low because both benign and malignant
      tumors appear as hypoattenuating perfusion defects. In addition, both focal and
      geographic nontumorous perfusion defects may be seen more frequently with spiral
      CTAP than with dynamic CTAP. Knowledge of common diagnostic pitfalls is necessary
      for accurate interpretation of spiral CTAP images.

PMID- 7624568
TI  - Medical savings accounts: a possible solution to the avalanche of medical billing
      paperwork.

PMID- 7624569
TI  - Radiologic history exhibit. The role of women in wartime radiology.

PMID- 7624570
TI  - Multilocular cystic renal tumor in children: radiologic-pathologic correlation.
AB  - Multilocular cystic renal tumor is a term that encompasses two histologically
      distinct but grossly indistinguishable lesions: cystic nephroma and cystic
      partially differentiated nephroblastoma (CPDN). Cystic nephroma is a segmental,
      purely cystic mass characterized by multiple septations composed entirely of
      differentiated tissues, without blastemal elements. CPDN is also a multiloculated
      lesion without nodular solid components, but its septa contain embryonal cells.
      Multilocular cystic tumors primarily affect boys during early childhood, with a
      substantial number of the lesions containing blastema (CPDN), and adult women,
      with lesions that more commonly lack septal blastema (cystic) nephroma). As a
      rule, nephrectomy is curative and the clinical course benign, but CPDN may recur
      locally. Although cystic nephroma and CPDN cannot be distinguished
      radiologically, failure to do so has no practical impact on management, since all
      of these tumors are surgically removed. However, the differential diagnosis
      includes other pediatric cystic renal masses that may require different treatment
      stratagems: Wilms tumor with cyst formation due to hemorrhage and necrosis,
      cystic clear cell sarcoma, cystic mesoblastic nephroma, cystic renal cell
      carcinoma, multicystic dysplastic kidney, and segmental multicystic dysplasia in
      a duplicated renal collecting system.

PMID- 7624571
TI  - Helical CT angiography with multiplanar reformation: techniques and clinical
      applications.
AB  - The technique and potential clinical applications of multiplanar reformation
      (MPR) of imaging data from helical computed tomography (CT) to display images of
      the blood vessels in the abdomen and the thorax are described. Helical CT was
      performed following bolus intravenous contrast material enhancement in patients
      with suspected tumor involvement of vessels in various regions of the body. The
      axial images were stacked to form a volume of imaging data from which a plane
      could be selected to display the desired vascular image in a two-dimensional
      format. Various techniques were used to change the image plane so that different
      vessels in different regions of the body could be displayed, including the
      splanchnic vessels around the pancreas, the portal veins and hepatic artery in
      the porta hepatis, the renal vessels, and the venae cavae and aorta. Rotation
      from a coronal or sagittal plane was necessary to display most vessels. The
      technique is practical and reproducible, but it requires that the operator be
      knowledgeable about vascular anatomy. Helical CT angiography with MPR has the
      potential to display vascular images that are similar to angiograms.

PMID- 7624572
TI  - Quality of clinical MR images and the use of contrast agents.
AB  - Attempts to optimize the quality of magnetic resonance images must balance the
      competing needs for high spatial resolution, high signal-to-noise ratio, a large
      number of sections, and a reasonable imaging time. These factors, which determine
      the ultimate image quality, are affected by a number of variables, including the
      field of view, the matrix and pixel size, choice of repetition time and echo
      time, section thickness, and the number of signals averaged. The manner in which
      these variables interrelate and their effect on the ultimate image quality are
      important in order to craft the most appropriate examination for each individual
      patient. A second major effect on soft-tissue contrast is the use of paramagnetic
      agents. The spectrum of utility of these agents within the central nervous system
      and the body is increasing. A large number of new agents are also being
      investigated, primarily for use outside the central nervous system.

PMID- 7624573
TI  - The cerebral ventricles: a computer-based interactive tutorial.
AB  - The computer-based tutorial, "The Cerebral Ventricles," enables the user to
      review the anatomy, imaging, and common pathologic conditions of the human
      cerebral ventricular system. The program runs on a workstation that includes a
      laser videodisk player and a videodisk with 21,000 still images plus motion
      sequences. By using a mouse to select specific portions of the anatomic diagram
      depicting the ventricles, the user can review different planes of normal gross
      anatomy, corresponding computed tomographic and magnetic resonance images of
      normal anatomy, images of gross specimens of different pathologic entities, and
      corresponding radiologic images. The motion sequences portion of the program
      shows reconstructed three-dimensional images of ventricular anatomy and helps the
      user gain a greater understanding of the complex anatomy as seen from all angles.
      Subprograms provide more detailed information about anatomic relationships,
      disease entities, and bibliographic references. "The Cerebral Ventricles" assists
      radiologists in gaining a greater understanding of the ventricles so that an
      appropriate differential diagnosis of an intraventricular lesion can be offered
      when such masses are encountered in clinical practice.

PMID- 7624574
TI  - The radiographic signs of arthritis: a computer teaching module.
AB  - This article describes the steps involved in production of a computer teaching
      module on the radiographic diagnosis of arthritis. The module was part of a
      research project aimed at producing seven computer teaching modules. Several
      staff radiologists and residents were involved, as well as a consultant on
      medical education. A generic shell program was used as a frame for all seven
      modules. The author of each module then filled in the empty pages of the shell
      with the appropriate text and images, along with additional short program
      scripts. The module on the radiographic diagnosis of arthritis described and
      illustrated the basic radiographic signs of arthritis. Practice cases were also
      included, and interactive and hypermedia features were implemented. The modules
      were then evaluated by means of task list tests and interviews. The experience
      was judged to have been successful, although the amount of time spent by some
      authors was much more than expected.

PMID- 7624575
TI  - The RSNA Learning Center and Home Page.

PMID- 7624576
TI  - General case of the day. Urethral autodigestion.

PMID- 7624577
TI  - US case of the day. Pena-Shokeir phenotype.

PMID- 7624579
TI  - [Nutrition, exercise and weight control].

PMID- 7624578
TI  - Pediatric case of the day. Orbital hydatid cyst.

PMID- 7624580
TI  - [Ultrasonic suction lipectomy. A mini-invasive treatment of obesity].
AB  - The safety of ultrasounds lipolysis in the treatment of local obesity and
      lipodystrophies versus suction lipectomy (less blood loss because of a lower
      impact on blood vessels network, and less mortality) induced us to combine these
      mini-invasive techniques in the treatment of obese patients. Between 1991 and
      1994 we treated 205 patients (146 females, 59 males, 18-59 range age), affected
      by 1st degree obesity (44.4%), 2nd degree obesity (27.3%) and 3rd degree obesity
      (28.3%), accordingly to the following schedule: 1) general anesthesia; 2)
      subdermal infiltration of the operating sites of a cold sodium chloride (0.9%)
      epinephrine solution (1:10(5), 8 degrees C); 3) 0.5 cm cutaneous incisions; 4)
      introduction of titanium tips as ultrasounds source; 5) insertion of suction
      lipectomy probes to remove the adipose tissue destroyed by ultrasounds; 6)
      drainage of the wide subcutaneous space; 7) setting of elastic bandages.
      Mortality was zero and very low side effects have been observed. We report an
      improvement of blood glucose and triglycerides level and blood pressure 30 days
      after surgery. Fair late postoperative improvement of the blood glucose tolerance
      test have been seen in 3 cases.

PMID- 7624581
TI  - [Tolerance of long-term protirelin tartrate treatment].
AB  - Synthetic TRH (TRH-T) has recently been used for the treatment of chronic and
      acute neurologic disorders. We studied the effects of long-term (30 days)
      refracted daily intramuscular administration of 4 mg TRH-T on neuroendocrine and
      cardiovascular system and on glucose and fat metabolism in 22 patients (mean age
      62.7 +/- 10.9) with chronic cerebrovascular disease. All subjects were submitted
      to ECG and arterial blood pressure determination and were assayed for TSH,
      thyroid hormone, PRL, glucose, creatinine, nitrogen, glutamine transaminase,
      cholesterol and triglycerides plasma levels before therapy (T0), after 30
      treatment days (T30) and after a 15 days washout (T45). Thyroid hormone, TSH and
      PRL serum levels were detected also after 15 days of TRH-T therapy (T15). In
      addition, TSH and PRL response to 200 micrograms iv TRH was assessed at T0, T30
      and T45. TRH-T administration did not cause significant alterations of
      neuroendocrine balance. Furthermore, we observed no changes in lipid metabolism,
      renal and liver function, arterial blood pressure, and ECG. In conclusion, TRH-T
      may be safely used in elderly patients with chronic cerebrovascular disease,
      independently to cardiovascular disorders.

PMID- 7624582
TI  - Prevention of interleukin-2-induced thrombocytopenia during the immunotherapy of
      cancer by a concomitant administration of the pineal hormone melatonin.
AB  - Thrombocytopenia is a frequent haematologic complication of IL-2 immunotherapy of
      cancer. Preliminary results suggest a role of melatonin in the regulation of
      platelet production, so a study was started to evaluate the influence of the
      pineal hormone on IL-2-induced thrombocytopenia. Of 25 lung cancer patients, 10
      were treated with melatonin alone, 7 received IL-2 alone and 8 patients were
      concomitantly treated with IL-2 and melatonin. Thrombocytopenia occurred in 3/7
      patients treated with IL-2 alone, and in none of those treated with IL-2 plus
      melatonin; this difference was statistically significant. Platelet number
      increased during IL-2 plus melatonin, even though not significantly; on the
      contrary, platelet number decreased during IL-2 alone. Platelet number observed
      in patients treated with IL-2 plus melatonin was significantly higher than in
      those who received IL-2 alone. Finally, melatonin alone did not substantially
      influence platelet number. These results show that melatonin may abolish IL-2
      induced thrombocytopenia. This might be due to an inhibitory effect of melatonin
      on macrophage-mediated platelet destruction, with a following increase in
      platelet number due to an enhanced IL-3 production in response to IL-2.

PMID- 7624583
TI  - [Strongyloides stercoralis in a region of northwestern Italy. An epidemiological
      note and presentation of a case of eosinophilic infiltration of the lung].
AB  - The Authors report a case of Strongyloides stercoralis infection in an
      autochthonous farmer from Piedmont (Northern Italy) presenting as an eosinophilic
      lung disease. After having briefly considered the epidemiological and clinical
      characteristics of the Strongyloides stercoralis infection, the Authors conclude
      by affirming that the appearance of migratory pulmonary infiltrates in
      autochthonous subjects or resident in Canavese area (Piedmont), especially if
      blood and sputum eosinophilia is present, should raise the possibility of
      Strongyloides-induced lung disease and lead to appropriate examination of sputum,
      feces, and eventually duodenal contents.

PMID- 7624584
TI  - Idiopathic avascular necrosis of the scaphoid. A case report.
AB  - Avascular necrosis of the carpal scaphoid is a common disorder after a trauma,
      i.e. a fracture or mild and repetitive injury. Sometime it can be associated with
      a systemic disease or chronic steroid intake. Rarely avascular necrosis is found
      in the absence of a known etiology and so termed "idiopathic". We report a case
      of idiopathic avascular necrosis of the scaphoid. A painful wrist of six months'
      duration was observed in a 62-year-old housewife. No history of trauma or steroid
      administration could be elicited. X-ray showed an osteolytic area with irregular
      edges surrounded by a ring of osteosclerosis at the proximal pole of the left
      scaphoid. This datum was confirmed by the magnetic resonance imaging.

PMID- 7624585
TI  - [Role of bone marrow plasma cell kinetics in the differential diagnosis of
      monoclonal gammopathies].

PMID- 7624586
TI  - [Hyper-IgD syndrome (HIDS)].
AB  - In 1984, Van der Meer first reported six patients with a long history of
      recurrent attacks of fever of unknown cause and a constantly elevated polyclonal
      IgD (> 100 U/mL); he suggested the acronym of "hyper-IgD syndrome" (HIDS). A
      recent literature review identified 60 cases (59 from Europe and 1 from Japan).
      The mean age was 27 years (range: 3-69 years). The family studies have shown a
      positive family history for periodic fever (40% out of the patients) but not for
      hyper-IgD. The median age at onset was 0.5 years (range from the first weeks of
      life to 53 years). The length of the febrile attacks, though variable, lasted
      from 3 to 7 days. The frequency of the attacks varied among the individual
      patients, but in general it was once a month or bimonthly. The fever was
      sustained in all 60 patients (from 38 degrees C to 41 degrees C), with a rapid
      rose, a plateau and a slow decline to normal values over 5 days. The associated
      clinical findings involve abdominal symptoms (pain, vomiting, diarrhea),
      recurrent peritonitis, lymphadenopathy, splenomegaly, articular manifestations
      (non-destructive recurrent arthritis) and skin lesions (vasculitis). The
      prognosis is benign. The aetiopathogenesis of HIDS is unknown. The role of IgD in
      the pathogenesis remains to be elucidated. The therapy is only supportive.

PMID- 7624587
TI  - [Molecular bases of anti-asthma action of corticosteroids].
AB  - Since it is now recognized that asthma is an inflammatory disease of the airways,
      the powerful antiasthmatic effects of corticosteroids are believed to be largely
      dependent on their broad anti-inflammatory activity. These drugs are the most
      effective asthma treatment currently available but, although they have been used
      for a long time, only recently the molecular mechanisms underlying their
      pharmacological actions are becoming clear. Corticosteroids bind to intracellular
      receptors which, upon ligand-dependent activation, interact with specific genomic
      DNA sequences thus leading to an increase or a decrease in the transcription rate
      of several target genes. Modulation of gene transcription by glucocorticoids
      underlies complex interactions involving their receptors, genomic DNA, nuclear
      chromatin, and other transcription factors. Furthermore, steroid hormones can
      also modulate gene expression at the post-transcriptional level. The anti
      inflammatory and antiasthmatic effects of corticosteroids are mediated by down-
      or up-regulation of specific target genes. Down-regulation of gene expression
      leads to a reduced synthesis of several cytokines and adhesion molecules. Up
      regulation results in increased production of lipocortins and beta 2-adrenergic
      receptors. A small minority of asthmatic patients do not respond to
      corticosteroids, and the mechanism underlying this steroid resistance is still
      under investigation.

PMID- 7624588
TI  - [References for evaluation instruments for quality assurance in rehabilitation-
      2. The IRES questionnaire for clinical aspects and research].
AB  - The article presents the comprehensive Indicators of Reha Status (IRES) patient
      questionnaire that can be used for assessment and outcome measurement in
      rehabilitation. We explain why the ?preventive-rehabilitative? orientation
      characteristic of the system of rehabilitation in Germany asks for particularly
      sensitive instruments as well as for inclusion of certain psychosocial variables.
      The results of validation studies are presented in some detail. In discussing
      possible applications of the questionnaire, we concentrate on its use for
      clinical practice (functional and psychosocial diagnostics, quality assessment).
      Finally, information is given on how to obtain questionnaires and the special
      computer programme for data entry and analysis.

PMID- 7624589
TI  - [Mutabor--ambulatory intensive promotion for patients with acquired brain
      damage].
AB  - Mutabor is an incorporated society offering intensive home treatment services for
      persons with acquired brain damage. While family respite is included, the
      intensive treatment provided is primarily focussed on transferring the potential
      acquired during clinical therapy into the patients' personal and occupational day
      to-day life and/or on building up new possibilities. Our treatment approach is
      aimed at enabling the patients to regain an individual and social identity while
      strengthening the patients' environment through respite care, counselling and
      ongoing therapeutic support. Mutabor works in close cooperation with medical
      doctors and therapists in the regional special clinics. Diagnosis and treatment
      however are weighted differently from what could usually be the case in a
      clinical setting; we rather undertake a highly individualized scrutiny of what
      would be practicable and desirable in a specific life situation. The cost is
      carried by the health insurance funds on a hourly or per diem basis. Our
      treatment concept is implemented by a team of 37 staff members from the fields of
      nursing, Occupational Therapy, logopedics/speech education, kinesitherapy, music
      therapy, social education, administration.

PMID- 7624590
TI  - [Modern technology and their use by severely handicapped patients--an interview
      with W. Irresberger. Interview by F. Fischbach].

PMID- 7624591
TI  - ["Cooperation between research and education"--5th Scientific Rehabilitation
      Meeting, March 1995 in Freyung].

PMID- 7624592
TI  - [Social policy and the problems of handicapped persons: the concurrent influence
      of ethics and power].
AB  - The paper describes in a very concise manner the importance of social policy in
      solving certain societal problems that are influenced on the one hand by ethical
      values and realpolitik power structures on the other. Social policy as a means of
      societal policy itself is not governed by ethical principles, it can however be
      used as a tool of transforming society. However, apart from the necessary
      political power, certain economic preconditions have to be fulfilled in order to
      realise sociopolitical ideas and a "socially just" distribution of the national
      income. Social measures thus are a compromise between societal policy and
      political and economic power, aimed at eliminating societal problems that have
      resulted, or could result, in political activities of individual groups. People
      with disabilities therefore should not be content with pointing out existing
      societal problems but should act as political pressure group in order to force
      solution of their problems.

PMID- 7624593
TI  - [The Early Rehabilitation Barthel Index--an early rehabilitation-oriented
      extension of the Barthel Index].
AB  - The Barthel Index has been shown to be a good measure of reduced activities of
      daily living which can be applied in routine clinical practice in a valid and
      reliable manner. However, patients with severe brain damage cannot be
      differentiated appropriately as floor effects show up with increasing severity of
      neurological impairment, e.g. in comatose and near- or post-comatose patients in
      early rehabilitation. Aspects of functional deficits relevant in early
      rehabilitation patients have been introduced to the Barthel Index in a separate
      section, the Early Reha Barthel Index (ERI). These aspects are: state requiring
      temporary intensive medical monitoring, tracheostoma requiring special treatment
      (suctioning), intermittent artificial respiration, confusional state requiring
      special care, behavioural disturbances requiring special care, swallowing
      disorders requiring special care, and severe communication deficits. Experience
      with the ERI gathered with 210 early rehabilitation patients and 312 patients
      with severe brain damage demonstrate that the extended scale permits
      differentiation of patients according to severity and to avoid floor effects.
      Patients can be allocated appropriately to different phases of rehabilitation,
      i.e., early rehabilitation of patients with very severe brain damage or
      rehabilitation of patients with severe brain damage. The ERI is quick,
      economical, and reliable. Given the high cost of early rehabilitation it is
      expected to be of special interest also to health care providers to ensure that
      the right patient is looked after in the right bed.

PMID- 7624594
TI  - [Evaluation of psychosomatic treatment--results of a catamnestic study].
AB  - The authors report first results of a program evaluation (n = 560) in a
      psychoanalytically oriented psychosomatic clinic. Based on a naturalistic design,
      the study includes three points of measurement (beginning and end of treatment, 1
      year follow-up) at which data were collected from patients and therapists. The
      article gives an overview of the general issues involved as well as of the
      methodological procedure and presents some catamnestic subjective and cost
      relevant singular outcome criteria.

PMID- 7624595
TI  - [School--and then what? On the occupational integration of severely handicapped
      adolescents--attempt at defining the current status].
AB  - The life situation of young people faced with severe consequences of their
      physical disablement is deteriorating due to general economic and worklife
      developments. Their right to occupational qualification is by no means
      universally honoured, and even those who have undergone vocational training find
      it increasingly hard to secure a job. This contribution therefore considers
      overall societal and economic conditions as well as trends forecast, discussing
      traditional and current views of successful life coping with or without
      remunerative work. Particular interest is taken in how disabled people themselves
      see their position in the working society. Problems of transition from school to
      post-school life settings are pointed out.

PMID- 7624596
TI  - [Vocational integration of physically handicapped persons--a regional study in
      the Regensburg district].
AB  - The present study had been aimed at tracing possible reasons for insufficient
      placement of people with physical disablement in the open labour market in the
      Regensburg region, at gaining insights on the prerequisites of and potential for
      improving vocational integration as well as at clarifying the relevance of
      alternative work and employment opportunities in terms of halfway and sheltered
      settings. Based on a structured questioning schedule, interviews were carried out
      with 10 experts, 32 physically disabled individuals and 30 employers concerning
      their placement notions and experience. Generally speaking, it was in particular
      found that insufficient placement cannot simply be attributed to economic trends;
      the groups interviewed, rather, differ in some of their underlying assumptions
      and expectations, a fact which impacts negatively on the integration process.
      Interaction of disabled and nondisabled persons hence requires greater attention.
      For the disabled, along with their educational-occupational qualifications,
      acquisition of communication and social skills is crucial in vocational
      integration, whereas the companies, in particular small and medium-sized ones,
      are in need of better information and counselling as well as appropriate supports
      to be provided by job or placement assistants when hiring physically disabled
      persons.

PMID- 7624597
TI  - Early pars plana vitrectomy without buckling procedure in cytomegalovirus
      retinitis-induced retinal detachment.
AB  - BACKGROUND: Retinal detachments induced by cytomegalovirus (CMV) retinitis can
      often be treated successfully with a buckling procedure combined with vitrectomy
      and silicone oil instillation, but this technique yields varying visual results.
      METHODS: To minimize operational trauma, pars plana vitrectomy and silicone oil
      instillation without additional buckling was performed in a series of 11
      consecutive patients with acquired immune deficiency syndrome (AIDS) and CMV
      retinitis-induced retinal detachment. Surgery was performed early in the course
      of the retinal detachment: 6 patients (55%) had an attached macula, and 7
      patients (64%) had a visual acuity of 20/200 or better. RESULTS: After a mean
      follow-up period of 5 months (range, 1-9 months) 9 patients (82%) had a
      completely reattached retina and 9 patients (82%) had visual acuity of 20/200 or
      better. The macula was reattached in all patients. A localized detachment of the
      inferior retina was noted in 2 patients (18%), and a second operation was
      required in one eye. Significant cataract formation occurred in two patients
      during the follow-up period. Proliferative vitreoretinopathy and increased
      intraocular pressure were not observed. CONCLUSION: Early vitrectomy without
      additional buckling procedures is justified in patients with CMV-associated
      retinal detachment because it stabilizes the retinal situation without major
      complications and improves visual function.

PMID- 7624598
TI  - A clinical study of the development of posterior vitreous detachment in high
      myopia.
AB  - PURPOSE: The correlation of age, axial length, and myopic chorioretinal atrophy
      with vitreous changes in high myopia were analyzed to investigate the development
      of posterior vitreous detachment (PVD) in high myopia. METHODS: The vitreous
      condition of 329 consecutive eyes with high myopia (more than -8.25 diopters (D)
      and more than 26.0 mm of axial length) was examined biomicroscopically with a +90
      D preset lens and a Goldmann three-mirror contact lens. RESULTS: The prevalence
      of PVD in high myopia was 12.5% in patients between 20 and 29 years of age, and
      it increased with age. The incidence of PVD in eyes with axial length of more
      than 30.0 mm was 60.7% and was statistically higher than the prevalence in eyes
      with an axial length of less than 29.9 mm (P < 0.01). Multiple logistic
      regression analysis showed that age and axial length were statistically
      significant factors in the development of PVD and lacuna formation in high myopia
      (P < 0.01), but the influence of chorioretinal atrophy was not significant.
      CONCLUSION: The results of this study suggest that liquefaction of the vitreous
      begins at a relatively young age in patients with high myopia and progresses with
      age and axial elongation, thus resulting in a frequent occurrence of PVD.

PMID- 7624599
TI  - Combination treatment of intraocular lymphoma.
AB  - BACKGROUND: Primary intraocular lymphoma is an uncommon clinical entity with poor
      visual and systemic prognosis. Optimal management of intraocular lymphoma remains
      uncertain. METHODS: Three patients with intraocular lymphoma, two of whom had
      documented CNS involvement, were treated based on a modification of the Sloan
      Kettering Cancer Center protocol for primary CNS lymphoma. All patients underwent
      diagnostic pars plana vitrectomy and histopathologic confirmation of primary
      intraocular large B-cell lymphoma. Treatment involved systemic chemotherapy with
      methotrexate and high-dose ARA-C, radiation therapy of the brain and orbits, and
      intrathecal methotrexate delivered via an Ommaya reservoir. RESULTS: Resolution
      of the ocular lymphoma was seen in all three patients, and resolution of the
      intracranial disease also was seen in the two patients with CNS involvement. All
      patients have remained disease free, with lymphoma in remission for at least 24
      months after completion of treatment. CONCLUSION: The Sloan-Kettering protocol
      for the treatment of primary CNS lymphoma also appears to be effective in some
      cases of primary intraocular large cell lymphoma. Furthermore, the Ommaya
      reservoir works well for intrathecal delivery of methotrexate in patients with
      CNS or leptomeningeal spread.

PMID- 7624600
TI  - The effects of phenylephrine 2.5% versus phenylephrine 10% on pupillary dilation
      in patients with diabetes.
AB  - PURPOSE: A prospective, double-blind study was conducted to compare the clinical
      efficacy of a combination of 1% tropicamide and 2.5% phenylephrine and a
      combination of 1% tropicamide and 10% phenylephrine for pupillary dilation in
      patients with diabetes. METHODS: Either 2.5% phenylephrine in one eye and 10%
      phenylephrine in the other eye, 2.5% phenylephrine in both eyes, or 10%
      phenylephrine in both eyes was administered to 127 consecutive patients with
      diabetes. All patients received 1% tropicamide in both eyes. RESULTS: There was
      no statistically significant difference in the amount of pupillary dilation
      between the three groups. CONCLUSION: As 2.5% phenylephrine may produce a lower
      incidence of side effects than the 10% concentration, we advise the use of the
      lower concentration, particularly among patients with diabetes, who already
      exhibit a higher prevalence of vascular disease and autonomic dysfunction.

PMID- 7624601
TI  - Antihistamines reduce blood-retinal barrier permeability in type I (insulin
      dependent) diabetic patients with nonproliferative retinopathy. A pilot study.
AB  - PURPOSE: To determine if histamine receptor stimulation mediates increased blood
      retinal barrier (BRB) permeability in patients with diabetic retinopathy, as it
      does in experimental diabetes. METHODS: Fourteen patients with type I (insulin
      dependent) diabetes and mild nonproliferative diabetic retinopathy were treated
      with combined astemizole, 20 mg, and ranitidine, 600 mg, or an identical placebo
      for 6 months in a double-masked fashion. Blood-retinal barrier permeability was
      measured by vitreous fluorometry at baseline and at 3 and 6 months. RESULTS:
      Permeability was significantly reduced in the group treated with antihistamines
      (P < 0.05) compared with the placebo group. There were no concomitant significant
      changes in systemic arterial blood pressure or HbA1c values. CONCLUSION: These
      pilot data suggest that histamine receptors influence permeability of the BRB in
      human diabetes. Further studies of the effects of antihistamines on diabetic
      retinopathy are warranted.

PMID- 7624602
TI  - X-linked familial exudative vitreoretinopathy. Report of one family.
AB  - BACKGROUND: Familial exudative vitreoretinopathy is an uncommon
      heredodegenerative disease with different types of inheritance and degrees of
      severity. METHODS: Findings in five affected members of a family in which the X
      linked mode of inheritance of familial exudative vitreoretinopathy is present are
      discussed. RESULTS: Patients presented with characteristic retinal exudative
      tractional detachment, temporal retinal vessel traction, capillary dilatation,
      neovascularization, and vitreous veils. CONCLUSION: A review of the 21 cases of X
      linked familial exudative vitreoretinopathy reported to date indicates a worse
      outcome in this mode of inheritance than in cases of autosomal dominant
      inheritance.

PMID- 7624603
TI  - Transretinal membrane formation in diffuse unilateral subacute neuroretinitis.
AB  - BACKGROUND: Diffuse unilateral subacute neuroretinitis (DUSN) is characterized by
      unilateral visual loss with vitreous inflammation, optic disc swelling, and the
      presence of gray-white lesions in the deep retina, and can be associated with
      intraocular nematode infection. To date, no cases of transretinal membrane
      formation in DUSN have been reported. METHODS: A 22-year-old woman was examined
      for a 2-week history of unilateral decreased vision and neuroretinitis. A
      subretinal nematode was identified and a diagnosis of DUSN was made. The nematode
      was destroyed with laser photocoagulation. An epiretinal membrane and traction
      retinal detachment persisted and the membrane was removed surgically, at which
      time it was noted to be transretinal, passing through a full-thickness retinal
      defect into the subretinal space. Laser photocoagulation was performed with the
      argon green laser (400 mW, 400 microns, 100 msec). Subsequent removal of the
      epiretinal portion of the transretinal membrane was performed via a pars plana
      approach. The membrane was studied by transmission electron microscopy (TEM).
      RESULTS: The laser photocoagulation was successful in destroying the nematode.
      Partial resolution of the neurosensory detachment resulted in marked improvement
      in visual acuity. The membrane consisted of a pauicellular collagenous stroma
      with scattered fibroblasts and mononuclear inflammatory cells. CONCLUSION:
      Removal of membranes affecting the macula may be of benefit in selected patients
      with DUSN.

PMID- 7624604
TI  - Sclerochoroidal granuloma in Wegener's granulomatosis simulating a uveal
      melanoma.
AB  - BACKGROUND: It is known that Wegener's granulomatosis may affect the eye, but
      macroscopically visible granulomas in patients with this condition have not yet
      been described. METHODS: Results of clinical, ultrasound, and histologic
      examination of a patient with Wegener's granulomatosis are presented. RESULTS: A
      sclerochoroidal granuloma in this patient simulated an uveal melanoma. It was not
      possible to unequivocally differentiate the lesion from a uveal melanoma on
      sonographic examination, but histologic examination confirmed the diagnosis of
      sclerochoroidal granuloma. CONCLUSION: Macroscopically visible sclerochoroidal
      granuloma is another facet of Wegener's granulomatosis, and in some cases may be
      mistaken for uveal melanoma.

PMID- 7624605
TI  - Vitreous cavity penetration of ceftazidime after intravenous administration.
AB  - PURPOSE: Penetration of ceftazidime, a third generation cephalosporin, into the
      vitreous cavity after intravenous administration was investigated. METHODS:
      Because antimicrobial penetration varies with surgical status of the eye and with
      inflammation, studies were conducted in phakic, aphakic, and aphakic,
      vitrectomized eyes in both normal and inflamed conditions. Ceftazidime 50 mg/kg
      was administered every 8 hours and vitreous cavity concentrations were tested at
      intervals from 2 to 72 hours after the initial dose. RESULTS: No penetration was
      found into control phakic and aphakic eyes, but drug concentrations were detected
      in inflamed eyes at 24 hours. Vitreous concentrations of ceftazidime in aphakic,
      vitrectomized eyes reached levels well above the minimal inhibitory concentration
      (MIC) for Pseudomonas organisms within 2 hours of intravenous administration in
      control eyes (8.5 micrograms/ml) and inflamed eyes (35.4 micrograms/ml).
      Inflammation and removal of the lens and vitreous significantly enhanced
      ceftazidime penetration at all time periods tested. CONCLUSION: Ceftazidime
      penetrates into the vitreous cavity of inflamed eyes after intravenous
      administration and achieves concentrations above the MIC for Pseudomonas
      organisms. Penetration is greatest in aphakic, vitrectomized eyes.

PMID- 7624607
TI  - Occult choroidal melanoma presenting as a serous macular detachment.

PMID- 7624606
TI  - Effects of hyperbaric exposure on eyes with intraocular gas bubbles.
AB  - BACKGROUND: Air travel is known to be potentially hazardous for patients with
      intraocular gas bubbles, and the external pressure changes associated with
      hyperbaric oxygen therapy and scuba diving could be similarly dangerous. METHODS:
      Rabbits with a perfluoropropane/air gas mixture filling approximately 60% of the
      vitreous cavity of the right eye were exposed to 3 different hyperbaric pressure
      profiles to an equivalent depth of 33 feet. The first group were a control group
      and were not exposed to hyperbaric pressures. The second group remained at an
      equivalent depth of 33 feet for 30 minutes, and the third group remained at 33
      feet for 1 minute. Both groups ascended to normal atmospheric pressure at a rate
      of 1 foot per minute. The fourth group remained at 33 feet for 1 minute and then
      ascended at a rate of 0.2 feet per minute. RESULTS: In all eyes with an
      intraocular gas bubble, intraocular pressure dropped to zero when the atmospheric
      pressure was increased, and rose to more than 50 mmHg when the atmospheric
      pressure was returned to normal. Pressures in excess of 50 mmHg were sustained
      for 10 minutes or longer in each rabbit exposed to one of the hyperbaric
      profiles. No significant intraocular pressure changes were observed in eyes
      without an intraocular gas bubble or eyes not exposed to hyperbaric pressure.
      CONCLUSION: Marked elevation in intraocular pressure occurs as a result of
      hyperbaric exposure in eyes with an intraocular gas bubble. Hyperbaric exposure
      is therefore not advisable for patients with intraocular gas bubbles.

PMID- 7624608
TI  - Cytomegalovirus retinitis in a patient with rheumatoid arthritis being treated
      with combination immunosuppressive therapy.

PMID- 7624609
TI  - A case of color vision abnormality and reduced amplitude of the 30 Hz flicker
      dark-adapted electroretinographic (ERG)

PMID- 7624610
TI  - Inferior peripheral iridectomy in patients receiving silicone oil. Rates of
      postoperative closure and effect on oil position.
AB  - BACKGROUND: Silicone oil tamponade is used in treating retinal detachments, but
      silicone-associated complications remain frequent. Keratopathy and acute
      pupillary block glaucoma are related to migration of silicone oil into the
      anterior chamber. Since 1985, many surgeons have created an inferior peripheral
      iridectomy (PI) at the time of surgery to prevent forward migration of the oil,
      but the rate of postoperative closure of the PI and the effect on oil position
      have not been well defined. METHODS: The charts of 292 patients undergoing
      silicone oil surgery were reviewed. The status of the PI and the oil position
      were determined throughout the postoperative period. RESULTS: Postoperative
      closure of the PI occurred in 40 (33%) of 121 aphakic eyes in the early
      postoperative period. Forward migration of the oil was highly associated with
      closure of the PI (32/40, 80%). Conversely, forward oil migration occurred in
      only 11% (9/81) of eyes with patent PIs. The rate of PI closure was significantly
      greater for patients with proliferative diabetic retinopathy (21/40, 52%) than
      for patients with proliferative vitreoretinopathy (11/58, 19%). CONCLUSION:
      Postoperative closure of the PI occurred in a significant fraction of eyes
      undergoing silicone oil surgery, was highly correlated with forward oil
      migration, and occurred most frequently in eyes with proliferative diabetic
      retinopathy.

PMID- 7624611
TI  - Pericellular PO2 and O2 consumption in monolayer cell cultures.
AB  - The current study was based on the uncertainty as to how well monolayer cell
      cultures growing in customary polystyrene dishes are supplied with O2. For dishes
      maintained in an air-5% CO2 atmosphere at 37 degrees C, microelectrode
      measurements revealed that the pericellular steady-state PO2 was 78 mm Hg in
      confluent bovine endothelial, 110 mm Hg in rat renal mesangial, and 0 (< 0.2) mm
      Hg in renal (LLC-PK1 and LLC-MK2) or hepatic (HepG2, Hep3B) epithelial cell
      cultures. These measured PO2 values were in good agreement with those calculated
      from Fick's law of gas diffusion, applied for the present culture conditions (one
      dimensional O2 diffusion, 0.52 cm medium height), the individual cell layer
      density and the tissue-specific rate of O2 utilization. Our results provide
      reasons to speculate that conventional monolayer cultures are often hypoxic when
      incubated in an air-5% CO2 atmosphere. Diffusion-limitations of cellular O2
      availability are to be taken into consideration when tissue cultures are used to
      study PO2-dependent processes.

PMID- 7624612
TI  - Alterations in diaphragm EMG activity during opiate-induced respiratory
      depression.
AB  - While opiate-induced increases in thoracic muscle tone may contribute to impaired
      ventilation during opiate anesthesia, the effects of high-dose opiates on
      diaphragm muscle activity have not been elucidated. The effects of the opiate
      agonist alfentanil (ALF, 500 micrograms/kg subcutaneously) on diaphragm (DIA) and
      intercostal (IC) electromyographic (EMG) activity in spontaneously ventilating
      adult rats were studied. EMG segments corresponding to inspiration and expiration
      were selected using an impedance plethysmographic respiratory waveform. Total EMG
      activity over a respiratory cycle was significantly greater in the DIA than in
      the IC. ALF produced a decrease in inspiratory and an increase in expiratory DIA
      EMG activity. These changes in diaphragm function following ALF were accompanied
      by significant respiratory depression. The effects of the alpha-2 agonist
      dexmedetomidine on ALF-induced changes in diaphragm and intercostal EMG activity
      were also examined. While dexmedetomidine alone had minimal effects on DIA
      activity, it significantly attenuated the ALF-induced increase in expiratory DIA
      EMG. The potential etiology and implications of these opiate-induced changes in
      diaphragm muscle function are discussed.

PMID- 7624613
TI  - Expiratory neural activities in gasping induced by pharyngeal stimulation and
      hypoxia.
AB  - The purpose was to characterize expiratory neural activities in gasping elicited
      during the aspiration reflex (AR) in hyperoxia and during hypoxia-induced
      gasping. In decerebrate, vagotomized and paralyzed cats, we recorded activities
      of inspiratory and expiratory cranial and spinal nerves. The AR was elicited by
      touching the epipharyngeal mucosa. In eupnea, spinal expiratory activities were
      greatly decreased during AR whereas laryngeal expiratory activities were
      increased. In hypoxia-induced gasping, both the laryngeal and spinal expiratory
      activities were reduced. All of the inspiratory activities were increased during
      both gasping and the AR. In addition, neural activities were below control levels
      following AR; activities gradually recovered to control levels. We conclude that
      spinal expiratory activities are inhibited during the AR and gasping. Results are
      consistent with the concept that medullary mechanisms for gasping are recruited
      by mechanical stimulation of the epipharynx. In hypoxia-induced gasping, the
      hypoxia, per se, causes a separate suppression of laryngeal expiratory
      activities.

PMID- 7624614
TI  - Respiratory and plumage gas volumes in unrestrained diving ducks (Aythya
      affinis).
AB  - Closed-circuit plethysmography and inert gas equilibration analysis were used to
      measure the volumes of gas in the respiratory system and plumage at the end of
      voluntary dives in unrestrained lesser scaup (Aythya affinis). Total (respiratory
      plus plumage) gas volumes were measured by helium dilution and estimated from
      body mass, body tissue density and buoyant force. These two techniques yielded
      results that differed by only 2.1 +/- 1.5%. Buoyancy decreased from a maximum of
      3.46 +/- 0.16 N at immersion to a minimum of 2.65 +/- 0.16 N at 1.5 m depth at
      the end of the feeding phase of voluntary dives. At 0.193 +/- 0.013 L BTPS, the
      respiratory system contributed 52% of the initial buoyancy and 65% of the minimum
      value. The increasing relative influence of the respiratory system on buoyancy
      was due to the loss of 47 +/- 5% of the air in the plumage layer during the dive.
      These data differ significantly from estimates based on restrained ducks, and
      this has implications for modelling of mechanical costs of diving, oxygen storage
      capacity and thermal insulation in foraging ducks.

PMID- 7624615
TI  - Factors influencing acid-base status during acute severe hypothermia in
      unanesthetized rats.
AB  - Blood acid-base changes were studied during acute hypothermia (4-6 h) induced by
      cold exposure in the unanesthetized rat. Stewart's quantitative analysis was
      applied as a complementary approach to determine the relative contributions of
      several non-respiratory components to the arterial acid-base response. Acute
      decrease in body temperature (TB) lowered PaCO2 (32.5 to 14.5 mmHg) and [HCO3
      ]a(24.20 mEq/L to 17.56 mEq/L), increased pHa (7.481 to 7.608) and diminished the
      [OH-]/[H+] ratio, but had no significant effect on [SID] or [Atot], although both
      total phosphorus [PT] and inorganic phosphate [Pi] increased. The acid-base
      changes found were intermediate between those predicted by alpha-stat and pH-stat
      hypotheses. Deviation from the regulative alpha-imidazole strategy was more
      apparent in the plasma than in the intraerythrocyte compartment. We conclude that
      blood pH changes observed were mainly caused by increased relative ventilation
      (lung ventilation per unit of CO2 removed) and by resulting changes in PCO2, with
      a minor metabolic component but without significant contribution from ionic
      shifts or changes in plasma protein concentration.

PMID- 7624616
TI  - Pulmonary blood flow distribution during acute hypoxia in conscious resting rats.
AB  - The effect of hypoxia on pulmonary blood flow (PBF) distribution were studied in
      11 conscious resting rats. Microspheres were infused into the inferior vena cava
      during normoxia (Nx), acute normobaric hypoxia (AHx, 10% O2, 30 min), and 30 min
      after removal of hypoxia (post-hypoxia, PHx). The lungs were cut into 28 samples,
      and relative scatter of specific PBF was calculated as (sample activity/sample
      dry weight)/(total activity/total lung dry weight). Changes in pulmonary arterial
      pressure (PAP) during AHx were determined in five additional rats. During Nx, PBF
      was distributed preferentially to the hilar, central regions, rather than to the
      periphery. AHx resulted in a decrease in PaO2 from 85.1 +/- 0.9 to 37.8 +/- 1.2
      Torr (mean +/- SE). Mean PAP increased significantly from 14.9 +/- 0.6 in Nx to
      21.2 +/- 1.0 Torr in AHx (mean +/- SE). However, PBF distribution remained
      unchanged. PHx restored arterial blood gases and PAP to control levels without
      changing PBF distribution. The results indicate that conscious resting rats do
      not demonstrate changes in PBF distribution during AHx.

PMID- 7624617
TI  - Hypoxic vasoconstriction in buffer-perfused rabbit lungs.
AB  - Isolated rabbit lungs were buffer-perfused under constant flow-conditions with
      separate control of alveolar (PAO2) and mixed venous (PvO2) O2 tension. Alveolar
      hypoxia caused an increase in pulmonary artery pressure (PAP) with sigmoidal dose
      dependency. Erythrocytes increased the strength of the hypoxic pulmonary
      vasoconstriction (HPV). The contractile and vasorelaxant responses to the onset
      and release of alveolar hypoxia, respectively, occurred within seconds. Kinetics
      of the PAP increase, but not the magnitude of response, were related to the
      velocity of PAO2 decline. In contrast, changes in PvO2, both in the absence and
      presence of erythrocytes, did neither provoke any pressor response nor amplify
      the response to concomitant alveolar hypoxia. Repeatedly performed HPV manoeuvres
      revealed excellent reproducibility, and long-term alveolar hypoxia (90 min)
      provoked a biphasic pressor response. We conclude that the isolated rabbit lung
      is a feasible model for the characterization of hypoxic vasoconstriction, with
      specific features hitherto not described for perfused lungs of other species.

PMID- 7624618
TI  - Relocation during incubation of endothelial nuclei in the chick chorioallantois.
AB  - Early in incubation the nuclei of the chick chorioallantoic capillaries are
      randomly distributed around the capillary lumen; later most of them are located
      on the portion of the capillary surface opposite the inner shell membrane. This
      is one of the complex of processes that results in progressive thinning of the
      diffusion pathway for gases between the external environment and the blood of the
      embryo. The present study quantified this nuclear "relocation". Our data show a
      progressive relocation of the endothelial nuclei from the tenth through the
      sixteenth day at an average rate of 6% per day.

PMID- 7624619
TI  - Proceedings of the XIth meeting of the World Society for Stereotactic and
      Functional Neurosurgery. Ixtapa, Mexico, October 11-15, 1993.

PMID- 7624621
TI  - An informal survey of stereotactic and functional neurosurgery.
AB  - The authors present information on the frequency of stereotactic surgical
      procedures for numerous clinical indications, based on the results of an
      international survey. Also presented is information on the interest levels of
      neurosurgeons in various new technologies and applications for stereotactic
      techniques.

PMID- 7624620
TI  - Late local and remote structural changes after capsulotomy for obsessive
      compulsive disorder.
AB  - Stereotactic subcaudate capsulotomy (SC) is used to treat medically intractable
      obsessive compulsive disorders (OCD). Although clinical improvement has been
      observed, post-SC structural correlates are lacking in this biological disorder.
      Our study provides imaging evidence for local and distant alterations in
      structures which may have an important role in the manifestations of OCD. Five
      OCD patients treated with SC received MR imaging for pre-SC planning, early (1-7
      days) post-SC assessment, and late (5-12 months) follow-up. The volumes of the
      anterior limb of the internal capsules, caudate heads, third ventricle, mamillary
      bodies, thalami, and hippocampal formations were digitally computed. Volumes from
      each of the serial imaging studies were compared. At 5-12 months post-SC, all
      patients showed reduction in volume of the anterior limbs of the internal
      capsules, caudate heads, thalami, and increased volume of the third ventricle
      (reflecting thalamic/caudate atrophy). 2-5 patients showed reduction in
      hippocampal formation volume. The post-SC reduction in volume of these
      structures, some far distant to the stereotactic lesion, suggests that the
      interrelationships of the anterior limb of the internal capsule, the
      caudate/thalamic nuclei, and possibly the pallidal and limbic systems are
      necessary for the manifestations of OCD and their variants.

PMID- 7624622
TI  - Computed tomography versus magnetic resonance imaging in stereotactic
      localization.
AB  - Neurosurgeons are often faced with a lesion that is obvious on magnetic resonance
      imaging (MRI), but not well-defined on computerized tomography (CT). However,
      questions remain regarding the distortion inherent in MRI images. Therefore the
      following comparative study was conducted. Five patients with intracranial
      lesions (1 lymphoma, 1 multiple sclerosis, 2 glioblastomas, and 1 AVM), underwent
      both CT and MRI for purpose of stereotactic biopsy or radiosurgery. The Brown
      Roberts-Wells CT and MRI compatible localizing rings were used. Coordinates of
      the left optic nerve-globe junction, the aqueduct, pineal and optic chiasm were
      recorded from both CT and MRI. With MRI, all three imaging planes, axial, coronal
      and sagittal, were used. Coordinates were calculated in millimeters and submitted
      to statistical analysis using Pierson correlation coefficients. In all, there
      were 17 CT, 17 MRI axial, 13 MRI coronal, and 13 MRI sagittal coordinates. The
      analysis revealed that of the MRI coordinates, the axial coordinates were more
      available and retrievable. Lateral targets, such as the left optic nerve-globe
      junction, were more difficult to identify on coronal and sagittal images and
      often lacked a full compliment of fiducial points for calculation. The
      correlation with CT was best for axial, followed by coronal and then sagittal MRI
      planes. Geometric image distortion occurs owing to nonlinearity of the magnetic
      field as well as magnet susceptibility to different tissues at an interface. We
      feel that MRI stereotaxy can be utilized in conjunction with CT for verification
      of lesion coordinates in relatively large lesions, and particularly in those not
      well delineated on CT.

PMID- 7624623
TI  - An image-guided stereotactic system for neurosurgical operations.
AB  - A new simulation system utilizing digital images (CT/MRI/SPECT) and an
      ultrasound/laser navigation system has been developed for image-guided surgery.
      Preoperative CT/MRI imaging does not always indicate the actual location of the
      lesion during intracranial operation, because the lesion may be displaced or
      distorted by operative procedures or CSF flowout. The authors developed an image
      integration system including an intraoperative ultrasonogram, which provides
      accurate information not only on the location of the deep-seated lesions but also
      surrounding anatomical structures during operation. The rationale of the system
      is to coordinate the three-dimensional axes of each image with the aid of a
      stereotactic subframe. Our simulation system has two ways. One simulation system
      works on a SUN workstation. At the preoperative simulation study: the entry point
      on the brain surface and the access route to the lesion are decided on from the
      three-dimensional CT/MRI images on the computer display. Then the configuration
      of the lesion from the operative view is displayed as an expected ultrasound
      image by reconstructing the CT and/or SPECT image. Another simulation system
      (HyperCAS) works on the HyperCard of a MacIntosh. The target point, the entry
      point and the trajectory are decided on and the three-dimensional location of
      these points is measured from serial CT images on the LCD display. At the time of
      operation, stereotactic craniotomy is performed using the laser navigator. The
      extent of the lesion at every depth in the surgical process is predicted from
      these images, and the access route to the lesion is easily corrected with the
      intraoperative ultrasound navigator.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7624624
TI  - Video registration virtual reality for nonlinkage stereotactic surgery.
AB  - We have combined three-dimensional (3D) computer-reconstructed neuroimages with a
      novel video registration technique for virtual reality-based, image-guided
      surgery of the brain and spine. This technique allows the surgeon to localize
      cerebral and spinal lesions by superimposing a 3D-reconstructed MR or CT scan on
      a live video image of the patient. Once the patient's scan has been segmented
      into the relevant components (e.g., tumor, edema, ventricles, arteries, brain and
      skin), the surgeon studies the 3D anatomy to determine the optimal surgical
      approach. The proposed intraoperative surgeon's perspective is displayed in the
      operating room at the time of surgery using a portable workstation. The patient
      is then brought to the operating room and positioned according to the planned
      approach. A video camera is trained on the patient from the proposed
      intraoperative surgeon's perspective. A video mixer merges the images from the
      video camera and the 3D computer reconstruction. This video mixer can vary the
      output intensity of the two input images between 100% of either and 50% of both.
      This visually superimposes the two images, not unlike a photographic double
      exposure. The patient's position and the 3D reconstruction are then adjusted
      until the images on the video mixer's output monitor are identical in terms of
      scale, position and rotation. This superimposition is facilitated by aligning
      various surface landmarks such as the external auditory canal, lateral canthus,
      and nasion. In some cases, such as with spinal tumors, capsules placed on the
      skin prior to scanning serve as fiducials.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7624625
TI  - PET in stereotactic conditions increases the diagnostic yield of brain biopsy.
AB  - We have recently described a technique allowing routine integration of PET scan
      data in the planning of stereotactic brain biopsy [Levivier et al:, Neurosurgery,
      1992; 31:792-797]. We now report our results in a consecutive series of 38
      patients that underwent combined FDG-PET and CT-guided stereotactic biopsy
      between June 1991 and January 1993. Stereotactic procedures were performed
      according to a standard protocol in which two biopsy trajectories were used
      whenever possible. This yielded to a total of 78 trajectories. In 31 patients, at
      least 1 trajectory was defined using an abnormality visualized on PET. The
      histological diagnosis was obtained in all cases. The diagnostic yield of each
      trajectory according to the FDG uptake of PET and contrast enhancement on CT
      showed that most low-grade tumors were found in hypometabolic/hypodense areas,
      glioblastomas were all diagnosed in areas with increased FDG uptake and contrast
      enhancement on CT while data for anaplastic astrocytomas were heterogeneously
      distributed. In the present series, 6 targets defined on CT were nondiagnostic;
      this never occurred when targets were defined on FDG-PET. In one case of
      anaplastic astrocytoma, the diagnosis was only made using a target defined on PET
      in a normal CT area; the second trajectory was made in a contrast-enhanced area
      on CT and was nondiagnostic. Because only structural images such as CT or MRI are
      available preoperatively, we analyzed separately the benefit of FDG-PET-guided
      biopsy in patients who have either an enhanced- or a nonenhanced lesion on CT. CT
      enhanced lesions were found in 27 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7624626
TI  - Stereotactic brain biopsies in AIDS patients: superior diagnostic yield with side
      cutting needle than with cup forceps.
AB  - Controversy still exists over the indicators for, and usefulness of, performing
      brain biopsies in AIDS patients with focal cerebral lesions. One of the sources
      of doubt is the relatively poor diagnostic yield in biopsying lesions in AIDS
      patients compared with patients who do not have AIDS. In our institution, we
      performed 25 CT-guided stereotactic biopsies using the Brown-Roberts-Wells system
      within a 1-year period. Of these, 11 were performed with a 2-mm-diameter cup
      forceps, and 14 with a 10-mm-long x 2-mm-diameter side-cutting needle. Abnormal
      tissue was obtained from all patients, but, in the first group, 5 (45%) biopsies
      were nondiagnostic, and, in the second group, none (0%) were nondiagnostic. Of
      the diagnostic biopsies, there was roughly an equal proportion of lymphoma,
      progressive multifocal leukoencephalopathy, and toxoplasmosis between the two
      techniques. It is surmised that the deciding factor leading to an enhanced
      diagnostic yield with the side-cutting needle was the larger amount of tissue
      obtained with this instrument.

PMID- 7624628
TI  - CT target selection in stereotactic anterior capsulotomy: anatomical
      considerations.
AB  - The first communications concerning stereotactic bilateral anterior capsulotomies
      were reported by Talairach and Leksell. This procedure has become established for
      the management of otherwise intractable anxiety neuroses and obsessive compulsive
      disorders, with a reported success rate of 70% in different series. It has been
      stressed that results are closely related to the extent of the lesion. The
      desirable lesion has a tubular shape with a length of 15-18 mm in the coronal
      axis. This shape is achieved by step withdrawal of a 4- to 5-mm electrode tip
      along a proper trajectory. A precise angulation of the trajectory is crucial to
      proceed without lesioning of the adjacent bordering caudate nucleus or putamen in
      the coronal plane. In the sagittal plane, it has to remain within the limits of
      the anterior capsula interna and avoid an excessive posteroanterior obliquity to
      ensure that the entry point through the cortex remains in the prefrontal
      noneloquent area. To achieve this trajectory, a target 5 mm posterior to the
      anterior border of the frontal horn, as seen on CT, at the level of the foramen
      of Monro has been suggested, along with a precoronal burr hole placed 20 degrees
      from the midline. Following these guidelines we have found the resulting lesions
      to be excessively anterior, with exclusion of their first 4- to 5-mm deep
      component. If the same target point is selected at two different axial levels to
      fix a trajectory, it usually results in an anteriorward trajectory that might
      require an entry point too close to the motor cortex, because the anterior horn
      reaches more rostrally as it deepens.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7624627
TI  - Interstitial chemotherapy with biodegradable ACNU pellet for glioblastoma.
AB  - For patients with nonresectable glioblastoma (GB) or recurrent GB, we have
      recently been using an interstitial chemotherapy with biodegradable polylactic
      acid pellets containing nimustine chloride (ACNU), in combination with
      superselective arterial ACNU injection, routine irradiation and chemotherapy. The
      ACNU pellets are prepared by mixing polylactic acid powder and ACNU, and then
      melting the mixture at low temperature and moulding it into a thin pellet.
      Pharmacological anticancer activity was experimentally demonstrated by the
      finding that a region of suppression was present surrounding an ACNU pellet
      placed in a B6 melanoma cell culture disc, but that no such suppression was
      present around a control pellet. In order to determine the spatial and temporal
      distribution of ACNU, a small pellet (ACNU: 0.6 mg) was implanted in the frontal
      lobe of rats. ACNU concentration determined by HPLC was 61.0 micrograms/g brain
      tissue on day 1. 22.5 on day 3, and 5.5 on day 7; small amounts of ACNU were in
      fact released for at least 4 weeks after implantation. This pellet was used for
      the clinical treatment of 11 GB patients. Four patients had several pieces of
      pellets implanted immediately after CT-guided stereotactic biopsy, and the other
      7 had pellets placed in residual tumor after partial removal at craniotomy. No
      ACNU was detectable in serum. CT studies obtained at subsequent appropriate
      intervals disclosed gas formation around the pellets, a slight increase in edema,
      and necrosis or decrease in CT enhancement of tumor beginning around day 12 after
      implantation. Bone marrow suppression did not occur, since ACNU was administered
      interstitially and in the range of 50-200 mg (average: 126 mg) per
      patient.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7624629
TI  - A table-mounted stereotactic system for digital angiography: a means of
      standardizing arteriovenous malformation measurement.
AB  - A detachable noninvasive table-mounted stereotactic device is described for use
      with digital radiography. The device is designed for standard two-view orthogonal
      projections but may be adjusted to allow for projections angled from the axial
      plane. When applied to the imaging of arteriovenous malformations (AVMs), it
      negates the influence of a variety of geometric and mechanical factors which
      would otherwise interfere with the determination of size. An accurate
      appreciation of AVM size, in turn, would allow a more reliable means of
      categorization of AVMs into distinctive groups for classification purposes and
      prognostication.

PMID- 7624630
TI  - How does the stereotactic workstation help the neurosurgeon?
AB  - At the KUL University of Leuven a workstation for the planning of neurosurgical
      stereotactic procedures has been developed. Its benefits are illustrated in three
      exemplary cases. The CT and/or MR images, acquired under stereotactic conditions,
      are transmitted via a PACS network (picture archiving and communication systems)
      directly to the stereotactic workstation in the operating theater. Target and
      entry point can be accurately defined on zoomed images. The trajectory can be
      checked and modified on all registered data sets and on resliced images along any
      plane. Maximum intensity projection of magnetic resonance angiography data sets
      along any arbitrary direction show the relative position of the blood vessels and
      the trajectory. During the preceding 32 months 29 patients were operated on using
      the stereotactic workstation. Postoperatively no new neurological deficit was
      observed in any of these patients. The workstation improves patient safety and
      increases the accuracy of neurosurgical stereotactic operations, because it helps
      the neurosurgeon to avoid blood vessels and/or important functional areas.

PMID- 7624631
TI  - Transformation of computed tomography and magnetic resonance images.
AB  - This paper discusses the transformation of computed tomography (CT) and magnetic
      resonance (MR) images, which maps the stereotactic volumetric cube of one
      examination to another. There are some mathematical problems connected with the
      present method. This approach provides a better visual detection and localization
      of the target point for the neurosurgeon or radiologist.

PMID- 7624632
TI  - Identification of the cerebral motor cortex by focal magnetic stimulation:
      clinical application to neurosurgical patients.
AB  - A figure-8 coil was designed that was capable of generating currents over a
      relatively limited area. In this study, we used the figure-8 coil to localize
      human cerebral motor cortex by transcranial magnetic stimulation and assessed its
      value as a diagnostic tool for neurosurgical disease. The subjects were 10 normal
      volunteers and 12 neurosurgical patients. The points obtaining a response were
      plotted and the response area was delineated for each stimulus output.
      Rectangular coordinates were subsequently determined for the C3-Cz-C4 line with
      the stimulation sites set 1.0 cm apart. Then amplitude and latency maps were
      displayed by a computer wave map program. In normal volunteers, the posterior
      margin of the site where a threshold +5% stimulus obtained a response from the
      THE or ADM muscles almost coincided with the central sulcus. The optimal areas
      were relatively narrow on the amplitude and latency maps. In the patient with a
      left frontal convexity meningioma, the left threshold +5% area for the THE and
      ADM muscles showed marked anterolateral shift. No threshold map could be obtained
      on the affected side in patients with metastatic tumor and astrocytoma. Low
      perfusion areas caused by moyamoya disease and arteriovenous malformations
      produced narrowing of the optimal zone on the threshold map of the affected side.
      Hyperexcitability of the motor cortex was recognized in the arteriovenous
      malformation patients. Transcranial focal magnetic stimulation is a useful
      noninvasive diagnostic method for identification of the human cerebral motor
      cortex. It provides important information about changes in the localization and
      excitability of the motor cortex in neurosurgical patients and should be helpful
      for treatment planning.

PMID- 7624633
TI  - Selective amygdalohippocampectomy: which route is the best? An experimental study
      in 80 human cerebral hemispheres.
AB  - Four different approach routes have been used to perform the selective
      amygdalohippocampectomy for the surgical treatment of epilepsy: transcortical
      through the middle T2 gyrus [1], translyvian through the deep sylvian fissure,
      transcortical subpial through the anterior T1 gyrus [2] and transcortical through
      the first temporal sulcus [3]. The choice between them, based on the advantages
      and disadvantages of each one, depends upon the different view angles they allow,
      and the parenchymal and vascular relationships they involve. This requires
      accurate knowledge of the microsurgical anatomy of this region and its features
      along the different acceding routes. The authors made an experimental study on 80
      adult cerebral hemispheres they randomly submitted to selective
      amygdalohippocampectomy through these four alternative approach routes. They
      measured the dimensions of the major temporal limbic structures, namely the
      amygdala and the hippocampus, and their distances from the brain convexity and
      the deep sylvian fissure along those acceding routes; they also registered the
      main distinct microsurgical features of each. The results emerge as anatomical
      guidelines useful to decide for each case which way is preferable to make
      amygdalohippocampectomy complete, safer and easier.

PMID- 7624634
TI  - Initial results of the nucleus FES-22-implanted system for limb movement in
      paraplegia.
AB  - The Nucleus 'FES-22' channel stimulation system has been developed for partial
      restoration of lower limb function in paraplegic individuals. One FES-22
      stimulator has been implanted in a 25-year-old paraplegic subject in November
      1991. Of the twenty 2.5-mm disc electrodes attached epineurally onto motor
      nerves, fifteen are capable of producing observable threshold and maximal muscle
      contractions with joint movements.

PMID- 7624635
TI  - Thoracoscopic ganglionectomy for hyperhidrosis.
AB  - Thoracoscopic sympathectomy for the treatment of hyperhidrosis has been carried
      out with techniques that involve either monopolar coagulation or laser injury to
      the T2 ganglion. Although this has the advantage of being minimally invasive, it
      has not been established whether these techniques are superior to complete
      ganglion excision, as carried out during open surgery. A new technique of
      complete T2 ganglion excision for palmar hyperhidrosis (with T3 ganglionectomy
      for axillary sweating) was developed using thoracoscopic techniques. Sixteen
      patients were treated with thoracoscopic T2 ganglion excision on the right side,
      and simple coagulation (Nd-YAG laser or monopolar) on the left side. Results were
      excellent with no posttreatment differences between hands at 1 year follow-up.
      However, long-term follow-up of these patients will be carried out to determine
      whether differences exist between these two techniques.

PMID- 7624636
TI  - Anatomical findings observed during microsurgical approaches of the
      cerebellopontine angle for vascular decompression in trigeminal neuralgia (350
      cases).
AB  - The authors report the anatomical pathological findings collected from 1979 to
      1992 in a series of 350 consecutive patients referred because of apparently
      idiopathic trigeminal neuralgia (TN) and operated on using a microsurgical
      keyhole approach of the cerebellopontine angle. In 20 cases (5.7%) the cause of
      the TN was a tumor or a vascular malformation, in 8 (2.3%) an atherosclerotic
      huge vertebrobasilar artery, all actually corresponding to symptomatic TN. Among
      the 322 others (= real idiopathic TN), only 10 (3.1%) had no visible compressive
      factor whilst 312 (96.9%) had one (or several) conflicting vessel(s): superior
      cerebellar artery in 90%, anterior inferior cerebellar artery in 23.6%, and a
      vein in 24.7%. In 35.7% of the patients, several neurovascular compressions (NVC)
      were found in association. Site(s) along the root, location around its surface
      and degree of severity of the conflicts were carefully studied. Of prime
      importance is the fact that, beside the localized lesions due to the NVC(s), a
      moderate to marked global atrophy of the entire root was frequently seen (in 67%
      of the cases) indicating that the NVC might not be the sole pathogenetic agent of
      the disease.

PMID- 7624637
TI  - Stereotactic radiation therapy and radiosurgery.
AB  - In all stereotactic irradiation procedures, a high dose is delivered to a
      relatively small target volume. Whether fractionated stereotactic radiotherapy is
      preferable (based on a therapeutic ratio) or a radiosurgical method (aiming at
      the precise and complete destruction of a tissue volume) depends on the
      definition and composition of the target. The methodologies can be grouped in
      closed-skull external focussed beam stereotactic radiosurgery/radiotherapy and in
      stereotactic implantation/injection of radiation sources. Although originally
      developed to treat functional disorders of the brain, stereotactic radiosurgery
      has been used most successfully for over 4 decades to treat cerebral
      arteriovenous malformations. Complete obliteration ranges from 30 to 50% after 1
      year are reported. At 2 years the results range from 72 to 90%. Clearly the
      outcome is influenced by patient selection. In the treatment of acoustic
      neurinomas follow-up data of larger series of radiosurgery show that the
      treatment performed under local anesthesia on an outpatient basis becomes
      comparable with the best microsurgery data. Using multiple isocenters and MR
      localization tumor growth control is achieved in more than 90% of cases, with
      hearing preservation of approximately 50%. Pituitary tumors with Cushing's
      syndrome, acromegaly, Nelson's syndrome, prolactinomas and nonsecreting adenomas
      have been treated with various stereotactic irradiation methods. Further
      refinement of both localization techniques, dose distribution and beam
      manipulation will make radiosurgery an attractive modality because of its
      noninvasive character and low morbidity. Only a small subgroup of patients with
      low-grade gliomas are candidates for stereotactic localized irradiation
      treatment, namely those with circumscribed tumors with only limited spread of
      tumor cells into the periphery. For this subgroup, which usually comprises not
      more than 25% of all low-grade gliomas, the results from interstitial
      radiosurgery compete with surgical resection. Apart from the possibility to
      define the borders of the treatment volume with serial stereotactic biopsies,
      there are dosimetric advantages of interstitial radiosurgery. Local single high
      dose treatment remains controversial for highly malignant infiltrative tumors,
      and significant treatment benefit remains to be documented. Radiosurgery can be
      used to effectively treat solitary brain metastases with less invasiveness and
      dissection of normal tissue, and with lower morbidity and less expense than open
      surgery.

PMID- 7624638
TI  - The exoscope--a frame-based video/graphics system for intraoperative guidance of
      surgical resection.
AB  - A system has been devised to focus a video camera mounted on a CRW stereotactic
      frame onto the surgical field and to integrate the video picture with a computer
      generated three-dimensional view of structures or targets deep within the brain.
      The surgical resection can then be done with the surgeon looking either at the
      composite picture on the video/computer monitor (as in almost all endoscopic
      surgery) or at the surgical field, to perform the resection using the
      conventional techniques most comfortable to the surgeon and most effective for
      the resection. The graphics platform on which the Exoscope program is built is
      the same as used for the RSA X-Knife stereotactic radiosurgery system. The X
      Knife graphics program allows the reconstruction of a target mass (such as
      intracranial tumor) and desired objects (such as surrounding vessels) with
      accurate registration to stereotactic coordinates derived from the CRW localizing
      system. By mounting a video system through an externally mounted endoscope on the
      CRW arc, it is possible to orient the video image with great accuracy to this
      same stereotactic space. The two images are superimposed on a computer/video
      console in the operating room. The surgeon visualizes a real-time video image of
      the operating field upon which is a graphical representation of the computer
      generated image of the target mass beneath the surface. In the corners are
      triplane orthogonal views through the center of target and a view parallel to the
      trajectory, so the surgeon may gauge his or her progress toward the
      target.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7624639
TI  - Stereotactic radiosurgery for glioblastoma multiforme.
AB  - From February 1989 to August 1992, 26 patients who presented with an initial
      pathological diagnosis of glioblastoma multiforme underwent tumor debulking (17)
      or biopsy (9), stereotactic radiosurgery (SR) and standard radiation therapy
      (dose range 50-66 Gy) as part of their primary tumor therapy. Presenting
      characteristics included median age of 55 years (range 20-79), Karnofsky
      Performance Score (KPS) median 82.5 (20-100), and median tumor volume 18.6 cm3
      (2.2-59.7). SR collimator size ranged from 2.25 to 4 cm with a central dose of 15
      35 Gy. Isocenter location, collimator size and beam paths were individualized
      using three-dimensional software such that the maximum possible solid angle was
      subtended without exceeding a 20% tumor dose gradient. The mean follow-up was
      10.9 months (6-19.5) with a median of 9.5 months. Statistical analysis was
      performed using Kaplan-Meier actuarial analysis developing predicted 12-month
      survival rates. There were no significant differences noted in patient survival
      for the parameters of biopsy versus debulking, single versus multiple isocenters,
      age, initial KPS, and patterns of steroid requirement. Radiographic recurrences
      were divided by location into central (within central SR dose) = 0, peripheral
      (within 1 cm of central dose) = 16, and distant (< 1 cm) = 4. Predicted 12-month
      survival was 24%, with a median survival of 9.5 months. These values are similar
      to previous results for surgery and standard radiotherapy alone [1]. The results
      suggest that radiosurgery, when used as a mode of primary therapy, offers little
      or no benefit in quality of life or survival as recurrences occur immediately
      outside or distant to the central SR field.

PMID- 7624640
TI  - Interstitial brachytherapy versus cytoreductive surgery in recurrent malignant
      glioma.
AB  - In selected patients with recurrent malignant glioma, interstitial brachytherapy
      has been advocated as an effective method for tumor control and prolonged
      survival. We are presenting our results with brachytherapy in patients with
      recurrent glioma, and comparing this technique with cytoreductive surgery. Twenty
      patients (9 male, 11 female) underwent stereotactic 125I implantation for
      recurrent malignant glioma (9 grade III, 11 grade IV). The average age was 43
      years and the average Karnofsky score was 76. All patients had received radiation
      therapy following their initial surgical procedure and 17 received chemotherapy.
      The median interval from initial procedure to implantation was 70.5 weeks. The
      median survival following implantation was 24 weeks and total median survival for
      the group was 94.5 weeks. This group was compared to a contemporary series of 22
      patients (16 male, 6 female) who underwent cytoreductive surgery for malignant
      glioma (10 grade III, 12 grade IV). The average age was 44 years and the average
      Karnofsky score was 76. All patients received radiation therapy following their
      initial procedure and 20 patients also received chemotherapy. The median interval
      from initial procedure to second procedure was 35.5 weeks, and from the second
      procedure to death was 28 weeks. The median survival for the group was 63.5
      weeks. The interval from the first procedure to the second procedure was
      statistically significant comparing the implant group (median 70.5 weeks) versus
      the cytoreductive surgery group (median 35.5 weeks; p = 0.04). No significant
      difference could be demonstrated between the interval from second procedure to
      death in the implant group (median 24 weeks) versus cytoreductive surgery group
      (median 28 weeks; p = 0.45).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7624641
TI  - Fractionated brachytherapy: catheter insertion and dosimetry.
AB  - The incorporation of the Omnitron device, a robotic isotope handling system, into
      a program of brachytherapy for glial tumors has made it possible to
      hyperfractionate treatment in 15-20 sessions over a 2- to 3-week period, which
      offers considerable theoretical advantage over conventional single dose regimens.
      Stereotactic catheter placement is by contrast-enhanced MR guidance, and takes
      advantage of the three-dimensional planning offered by voxel orientation. Initial
      placement is based on orientation to the three customary planes, with oblique
      planes added to define intercatheter placement more accurately. Catheters may be
      placed asymmetrically through the tumor or even at different angles of insertion
      to get the optimal conformation. Dosimetry is based on three-dimensional
      reconstruction in the Omnitron planning console, and takes advantage of the
      optimized localization of each catheter position. High-dose isotope insertion is
      performed robotically, with isotope position and dwell times controlled by
      computer. The phase I study demonstrates a wide safety margin and suggests better
      survival than would be expected with conventional management.

PMID- 7624642
TI  - Neuropathology of intracranial arteriovenous malformations following conventional
      radiation therapy.
AB  - Conventional fractionated radiation therapy was used in 15 patients to treat
      arteriovenous malformations (AVMs) of the brain deemed inoperable or incompletely
      obliterated using endovascular or surgical techniques. The AVMs measured from 0.8
      to 85 cm3 (mean 28.2 cm3; median 24 cm3). Angiography in 12 patients 1-21 years
      following radiation therapy demonstrated no significant change in 7, slight
      reduction in 2, near complete obliteration in 1, and complete obliteration in 2.
      Magnetic resonance imaging further demonstrated apparent obliteration in one
      other case. Three irradiated AVMs were available for pathological examination
      following fatal recurrent hemorrhage after 21 years in case 1 and following
      surgery after 5 years in cases 2 and 3. Doses of 20 and 45 Gy were delivered to
      the area of the AVM in 10 and 15 fractions with a 6-MV linear accelerator in case
      1 and in cases 2 and 3, respectively. A blinded histopathological comparison was
      made of the latter cases and three AVMs removed at surgery that were not
      previously irradiated and that were comparable in size, number of arterial
      feeders, and location within the brain. Segmental hyalinization of some blood
      vessels was seen in both irradiated and nonirradiated cases. The single
      postmortem specimen showed extensive thrombosis but a patent nidus. The findings
      are in keeping with the clinical impression that conventional fractionated
      radiation therapy fails to alter the natural history of cerebral AVMs. The
      favorable outcome of radiosurgery on small- to medium-sized AVMs appears
      attributable to the shorter duration of therapy using relatively high-dose
      prescriptions to the nidus.

PMID- 7624644
TI  - Easy preoperative planning of deeply located brain lesions using external skin
      reference and 3-dimensional surface MRI.
AB  - Open skull surgery of deeply located intracerebral lesions requires precise
      determination of the treatment area in 3-dimensional (3-D) space. 3-D MRI can
      give important additional information in presurgical determination of the
      surgical approach to the target, taking into account highly functional brain
      areas and important vascular structures. The day before surgery, a grid composed
      of 9 tubings intersecting at 90 degrees at 1 cm intervals and filled with a CuSO4
      solution is firmly attached to the skin of the patient's head in the presumed
      region of the craniotomy. A 3-D turbo-FLASH sequence is then performed in the
      sagittal plane after intravenous Gd-DOTA injection on a 1T Magneton. 3-D surface
      reconstruction of the cortical gyri and sulci is performed. Once the gyri are
      identified, the 3-D program is then implemented in order to perform a color
      display of the cortical veins and of the tumor boundaries. The surgical access is
      then chosen by the surgeon, taking into account highly functional areas. Finally,
      the boundaries of the tumor are projected on the cortex reconstruction and on the
      external reference placed on the skin. The entry place for surgery as well as the
      size of craniotomy are drawn on the skin and the tubed grid is removed. The
      accuracy of this method tested in 9 patients with deeply located brain tumors or
      arteriovenous malformations was very satisfactory.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7624643
TI  - Stereotactic linear radiosurgery for cavernous angiomas.
AB  - Optimal management of symptomatic cavernous angiomas (CA) located in the thalamus
      and the brainstem is problematic. Clinical and radiological (MRI) follow-up
      series suggest that having hemorrhaged once, recurrent hemorrhage with
      progressive neurologic dysfunction may commonly occur. We have therefore chosen
      to treat these lesions when first symptomatic with stereotactic linear
      radiosurgery (SLR). We now report, after a median follow-up of 27 months, 12
      patients with CAs (9 women, 3 men, mean age 40 years) treated in this fashion.
      Ten patients presented with hemorrhage (3 had more than one hemorrhage): two
      patients had new onset seizures. All patients had enhanced MRI/MRAs
      characteristic of CA. There were five brainstem and five thalamic CAs, and one
      each in the temporal lobe and insula. Cerebral angiograms were done in 8 patients
      for comparison with their respective MRAs. Only one CA was visualized in the late
      venous phase on cerebral angiogram and identical vascular features were
      appreciated on the MRA. The diameter of the CAs ranged from 1.0 to 3.0 cm with a
      mean of 1.6 cm. Dosimetry planning was based on MRI/CT features and the mean dose
      at the isocenter was 2.167 cGy (range = 2,000-2,500 cGy) delivered with a mean
      collimation diameter of 1.46 cm (range = 1.0-2.0 cm). All 12 patients continued
      to improve neurologically after SLR and had MRI-documented changes in their
      lesions: in general, the lesions became smaller and signal characteristics
      converted to methemaglobin. However, 1 patient had an early post-SLR hemorrhage,
      documented by MRI, at 4.5 months.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7624645
TI  - Stereotactic radiosurgery for the treatment of low-flow carotid-cavernous
      fistulae: results in a series of 25 cases.
AB  - 25 patients with low-flow carotid-cavernous fistula (CCF) underwent radiosurgery
      between 1977 and 1992. 22 had spontaneous low flow fistulae and 3 traumatic high
      flow fistulae which had been previously treated with internal carotid trapping.
      The mean preoperative symptomatic period was 12.2 months (4-24 months). Fistulae
      were classified according to Barrow's classification. Type T was added for
      traumatic, high-flow fistulae with flow reduction after internal carotid
      trapping. 11 cases were of type B, 4 of type C, 7 of type D and 3 of type T. The
      target point for radiosurgery was calculated from selective internal or external
      carotid angiograms. Stereotactic radiosurgery was performed with a cobalt source,
      with 5- to 10-mm collimators. A total dose of 30-40 Gy was delivered in all
      cases, except 1 posttraumatic case in which the dose was 20 Gy. The follow-up
      period ranged between 14 years and 15 months (mean: 49.76 months). 20 of the 22
      low flow fistulae (90.9%) completely closed in a mean period of 7.5 months
      (range: 2-20 months) after radiosurgery. Improvement of the symptoms began at a
      mean period of 2.37 months (range: 0.5-14 months). There were no recurrences, the
      follow-up period ranging between 14 years and 15 months. 100% of type B CCF
      closed after a mean period of 5.9 months, 75% of type C closed after a mean
      period of 12.66 months, and 85.7% of cases of type D closed after a mean period
      of 8.16 months.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7624646
TI  - Stereotactic radiosurgery may be effective in the treatment of idiopathic
      epilepsy: report on the methods and results in a series of eleven cases.
AB  - Between 1982 and 1991, 11 patients (4 male, 7 female) ranging in age from 16 to
      42 years who had been diagnosed with idiopathic focal epilepsy resistant to
      medication, were treated with stereotactic radiosurgery. The preoperative
      symptomatic period was 3-24 years. The process of localizing epileptic focus was
      based on chronic electrocorticography with flexible electrodes introduced into
      the subarachnoid space through single burr holes, and left in place during a
      maximum of 7 days until a clinical seizure was recorded. In most cases the
      procedure had to be repeated until localization was clear. This process was aided
      by a computer-assisted automatic analysis procedure. Final confirmation of focus
      location was done with depth electrode recording in most cases. Stereotactic
      radiosurgery was performed with a 60Co gamma source using 10 mm collimators,
      except in two cases in which a betatron was used. The estimated dose was 10-20 Gy
      at the isocenter. Four of the 11 patients (36%) were medication- and seizure-free
      after a mean follow-up of 102.5 months. Five patients (45%) presented a reduction
      of seizures of 98, 89, 86, 75 and 75%, respectively. Two patients did not respond
      to treatment. Seizure reduction began after a delay period of 2-12 months except
      in 2 patients and in most cases seizure rate decreased progressively during
      several months (range: 3-48) postoperatively until stabilization. No
      complications related to irradiation were recorded. Doses effective for epilepsy
      are much lower than those for producing cerebral lesions, so the mechanism is not
      destruction of the focus of the pathways spreading the epileptic
      activity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7624647
TI  - Neurobiologic effects of radiosurgery: histologic, immunohistochemical and
      electron-microscopic studies of a rat model.
AB  - Spinal cords of rats were irradiated with a single fraction of 14-36 Gy (group A)
      or 55 Gy (group B) and examined by light and electron microscopy. Degeneration
      and reduced numbers of motor neurons were found even at an early stage in group B
      animals. Necrosis in the spinal cord was found at a later stage. The
      ultrastructure of vessels around areas of necrosis showed degeneration of
      pericytes and vacuolar changes of vascular walls. This study indicates that
      single, high-dose irradiation causes direct effects on neurons at early stages
      and degeneration of vascular walls followed by necrosis at a later stage.

PMID- 7624648
TI  - Reliability of amygdalohippocampal volume measured directly on MRI films.
AB  - Volume measurement of the amygdalohippocampus on MRI may provide important
      information for epilepsy surgery. This study investigated the reliability of
      direct volume assessment (DVA) versus computer-assisted measurement (CAM) of
      amygdalohippocampus. DVA was carried out by counting the number of squares
      occupied by amygdalohippocampus in a transparent mm2 overlay used on both
      sagittal and coronal films. CAM was achieved using the 'thresholding and tracing'
      automated technique. Seventeen patients undergoing language-dominant left
      temporal lobectomy were studied. Mean volume as determined by the CAM was 4.99 +/
      1.31. In DVA, the mean volume was 5.05 +/- 1.23 (r = 0.974). Reproducibility of
      the volume measurement was tested by repeating measurements 5 times on 5 patient
      samples of amygdalohippocampal complex in DVA, and 3 times on 4 samples in CAM.
      The mean coefficient of variation for amygdalohippocampal volume was 6.9 +/- 3.2%
      in DVA and 3.9 +/- 2.0 in CAM. We also tested a more simplified method of
      assessing amygdalohippocampal volume by calculating the left to right volume
      ratio from MRI scans (2-40 films for each sample). Volume ratios determined
      directly from MRI films made in different months (14 samples) and of different
      sections (coronal and sagittal series, 18 samples) correlated well with each
      other (p < 0.01). Direct assessment of amygdalohippocampal volume can be used
      effectively for preoperative evaluation of the patient with epilepsy.

PMID- 7624649
TI  - Stereotactic resection of brain metastases in eloquent brain.
AB  - We have treated 14-patients with metastatic tumors located in eloquent cortical
      areas by a stereotactic-guided keyhole craniotomy and total microsurgical
      excision utilizing the Pelorus stereotactic device. Patients ranged in ages from
      26 to 82 years with a median age of 59 years. There were 9 women and 5 men. Ten
      patients presented with hemiparesis and 4 with aphasia. Primary tumor location
      was lung in 7, colon in 2, melanoma in 2, and breast, renal, and bone in 1 case
      each. Gross total resection was accomplished in all cases, with postoperative
      imaging confirmation of complete removal. Single metastatic tumors were removed
      in 12 cases, and multiple lesions in 2 cases. Twelve patients had postoperative
      whole brain irradiation (30 Gy/10 fractions); 2 patients had previously received
      whole brain irradiation, yet demonstrated tumor growth. Complete resolution of
      neurologic deficits was accomplished in 8 patients, 3 had improved and 2 were
      unchanged. One patient had resolution of preoperative deficit but developed
      hemiparesis secondary to a hemorrhagic infarction contralateral to the operative
      site. Nonneurologic morbidity includes deep venous thrombosis in 3 patients, and
      pneumonia in 1. Thirty-day perioperative mortality is zero, and to date no
      patient had died of intracranial disease. We believe that with the assistance of
      stereotactic localization, metastases in vital regions of the cortex can be
      removed with very low neurologic morbidity, and with a high proportion of
      patients having improvement in their level of neurologic function. The morbidity
      in this series compares favorably with that of stereotactic radiation series
      reported in the literature with local disease control and resolution of
      neurologic deficits that equals or exceeds stereotactic radiation.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7624650
TI  - Zamorano-Dujovny multipurpose neurosurgical image-guided localizing unit:
      experience in 866 consecutive cases of 'open stereotaxis'.
AB  - We describe the Zamorano-Dujovny localizing unit which consists of a ring-shaped
      headholder held on the patient's head by three or four variably placed fixation
      pins, thereby avoiding interference with the flap sites or craniotomy. The base
      ring is mounted intraoperatively on a special adapter that allows any patient
      positioning including supine, lateral prone, 3/4 prone, sitting, etc. Imaging
      studies, such as computed tomography, magnetic resonance imaging, x-ray, digital
      angiography, and digital subtraction angiography can be performed with the
      headholder anchored in place for multimodality image localization. Surgical
      draping can be done over the ring to provide a completely sterile field. An
      arc/quadrant localizing device can be mounted on any four alternative positions
      according to the neurosurgeon's preference. PC-compatible software gives the
      setting for any possible mounting. Intraoperatively the localizing unit can be
      used in a 'fixed' permanent setting or as a 'nonfixed' system to provide
      intraoperative three-dimensional orientation. Different types of instruments
      compatible with the unit extend its capabilities, such as 'bayonet'-type brain
      retractors (cylinders and speculum) that keeps the surgical corridor unobstructed
      from the arc. As an alternative, in the nonfixed setting, self-retaining arms are
      fixed to the base ring and brain retractors and conventional microsurgical
      techniques can be used without any mechanical obstruction.

PMID- 7624651
TI  - Computer-assisted CT-guided stereotactic biopsy and brachytherapy of brain
      tumors.
AB  - From March 1991 to September 1993, 26 patients (aged 4-78 years) with brain
      tumors (4 glioblastoma multiforme, 10 nonglioblastoma multiforme, 1 mixed
      oligoastrocytoma, 2 carniopharyngiomas, 2 meningiomas and 7 metastases) were
      treated with stereotactic techniques at the Centro Internacional de Restauracion
      Neurologica, La Habana, Cuba. A total of 28 stereotactic surgical procedures were
      performed with no operative mortality; they included biopsies in all cases, 1
      stereotactic microsurgical resection and 12 permanent implants of 192Ir, followed
      by external beam fractionated radiation therapy (40-60 Gy). The present paper
      shows that the combined use of a stereotactic approach, a comprehensive and
      reliable stereotactic dosimetric planning system, stereotactic brachytherapy with
      192Ir and complementary percutaneous radiation treatment constitutes a promising
      strategy for brain tumor management.

PMID- 7624652
TI  - Genetic versus histological grading in stereotactic biopsies.
AB  - With diagnostic stereotactic biopsies in astrocytoma sometimes false results will
      be encountered. A false positive result is defined as a histological diagnosis
      which is afterwards proved to be untrue. Although this happens very seldom (1-2%)
      in characterizing the tumor type (e.g. astrocytoma versus lymphoma), there is a
      probability of undergrading in malignant astrocytomas due to regional
      heterogeneity in malignancy grade. The issue of 'sampling error' has been
      addressed by many authors. It was shown that undergrading in astrocytomas is a
      likely event in fibrillar astrocytomas that often show geographically distinct
      areas of well and poorly differentiated elements. In a recent study on
      histological grading versus genetic characterization of heterogeneous
      astrocytomas we published that low-grade areas within high-grade malignant
      astrocytomas have already the genetic features of high-grade malignancy.
      Therefore, particularly in stereotactic biopsies which contain relatively small
      samples of tumor tissue, this fact is of paramount importance. Undergrading may
      lead to withholding radiotherapy from the patient and to falsification of long
      term survival results in series of so-called low-grade astrocytomas. We like to
      stress the importance of taking biopsies from different parts of the tumor,
      especially from parts with different density enhancement to contrast with CT
      scanning, and will discuss the technical advancements made in the genetic grading
      of astrocytomas. Particularly loss of heterozygosity of chromosome 10 and
      eventually amplification of the EGFR indicate a high grade of malignancy.

PMID- 7624653
TI  - Morbidity of chronic recording with intracranial depth electrodes in 170
      patients.
AB  - A consecutive series of 170 patients who have been submitted to intracranial
      depth electrode recordings is reviewed to assess the overall morbidity of the
      technique. Most patients had bitemporal and frontal electrodes inserted and were
      monitored for an average period of 18 days. A surgically amenable focus was found
      in 85% of the cases. There were 4 cases of infection including 2 cerebral
      abscesses which required surgical evacuation. One patient with frontal lobe
      atrophy developed an acute subdural hematoma after electrode implantation. There
      was no death or neurological deficit in the entire series. Morbidity was
      encountered mainly in the neuropsychological sphere, several patients having
      developed transient postictal psychosis after repetitive seizures. Our recording
      technique has been associated with low surgical morbidity. Patients undergoing
      depth electrode recordings should be closely monitored to minimize the occurrence
      of psychotic episodes associated with drug withdrawal and increased seizure
      frequency.

PMID- 7624654
TI  - Three-dimensional display in the evaluation and performance of neurosurgery
      without a stereotactic frame: more than a pretty picture?
AB  - Display of three-dimensionally rendered images derived from radiological data
      sets is often suggested to be useful for surgical and radiation treatment
      planning in neurosurgery. Nevertheless, physicians will often note (off the
      record) that these rendered images are 'just a pretty picture' and are not
      clinically useful. This paper will discuss our three-dimensional rendering and
      quantitative analysis software and its primary use in evaluating and utilizing
      frameless stereotactic methodologies. A variety of concepts and techniques will
      be discussed. Specifically, a computer graphic and statistical-based technique
      will be presented that enables timely and measurable image registration between
      radiological image space and the coordinate system of computer-driven surgical
      devices in the operating room. This technique may be utilized to maintain a
      surgeon's orientation and to quantitatively and graphically monitor the position
      of probes and instruments in the surgical field. Three-dimensional quantitative
      results of phantom testing will be presented. Correlation to and validation
      against stereotactic imaging calculations using the compass stereotactic system
      will also be discussed. These computer graphic/statistical-based techniques are
      applicable for evaluating the accuracy of any frameless stereotactic device
      including, but not limited to robotic arms, spark gap, LED and magnetic field
      digitizers.

PMID- 7624655
TI  - Three-point transformation for integration of multiple coordinate systems:
      applications to tumor, functional, and fractionated radiosurgery stereotactic
      planning.
AB  - The accuracy of an optimized three-point transformation method and its usefulness
      for integrating multiple independent coordinate systems has been described. Such
      integration can be implemented to accomplish complex stereotactic procedures
      which may require the use of multiple image data sets and combinations of frame
      based and frameless stereotactic systems. This report details the application of
      an optimized transformation for intracranial lesion biopsy and/or resection,
      radiofrequency pallidotomy for treatment of Parkinson's disease, and fractionated
      stereotactic radiosurgery in a total of 68 patients. For approach to intracranial
      lesions, a noninvasive definition of image coordinate systems with multiple
      radiodense scalp markers was cross-registered with a standard stereotactic
      guidance system. This method allowed for elective acquisition of stereotactic
      image sets without requiring head frame fixation until the time of the operative
      procedure. In planning pallidotomy procedures, spatial cross-registration of CT
      and MR image coordinates were performed to target the posteroventral pallidum. CT
      coordinates were defined by the standard picket fence algorithm while MR images
      were referenced with multiple scalp markers. The addition of MR data sets
      improved anatomic resolution in the regions of the basal ganglia and commissures.
      Fractionated radiosurgery was accomplished by cross-registration of CT, MR, and
      plain radiographs using BRW localizers coupled with multiple scalp markers. A
      daily check of target positioning was performed with the BRW angiograph
      localizer. The average calculated error was 2.83 mm with a standard deviation of
      1.66 mm which remained within the average scan slice thickness of 3.63 mm. In all
      cases surgical targets were reached without complication.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7624656
TI  - Imaging techniques and computers.
AB  - Imaging technology has been the pacesetter of stereotactic technique since its
      introduction in clinical practice. Quite recently, the extraordinary quality of
      diagnostic neuroimages and the growing availability of computing power has
      widened the field of applications of stereotaxy suggesting, at the same time,
      substantial evolution of its instrumentation. Fusion of multimodal digital
      images, integration of morphological and functional data, and dimensional
      rendering techniques have become powerful 'navigational aids' for tissue
      sampling, functional procedures and image-guided endoscopic surgery.
      Radiosurgical dose planning systems integrated with image processing and computer
      graphics routines allow efficient interactive evaluation of tissue-dose volumes
      superimposition in brachytherapy and external beam focused irradiation.
      Volumetric guided open surgery, assisted by intraoperative acquisition of
      stereotactic echographic and microscopic images, allows satisfactory treatment of
      deep-seated cerebral lesions. Further improvement is to be expected with the
      implementation of the ongoing development of localizing solutions totally
      integrated with the microsurgical instrumentation.

PMID- 7624658
TI  - Interactive intraoperative localization using an infrared-based system.
AB  - Conventional stereotactic surgery has evolved from a ring-based system with a
      simple software which calculated few parameters to frameless intraoperative
      localization systems that provide the surgeon with real-time localization and
      correlation with several imaging modalities. The localization system described in
      this paper is an opto-electronic system that uses infrared emitters and three
      precalibrated CCD cameras. The system was chosen among others for the following
      reasons: it tracks target points defined by up to 256 miniature light emitting
      diodes, and its accuracy in locating the spatial position of a diode marker in
      the operating volume 1.0 x 1.0 m at a distance of 2.0 m is 0.1 mm with a
      resolution better than 0.01 mm. Systems like this one can track and define the
      position and orientation of any object in the field view of the camera. This is
      done by attaching a few small infrared emitters (light emitting diodes) to the
      surface of each 'rigid body' (surgical instrument) being tracked. Subsequently,
      through a calibration process a corresponding rigid body file is created. This
      rigid body file represents this particular object (i.e. surgical tool,
      microscope) and defines a local coordinate system that identifies each
      translation and orientation of that tool with respect to the camera coordinate
      system. This in turn is transferred into the computed tomographic/magnetic
      resonance imaging coordinate system by a process referred to as coordinate
      matching. Fiducial markers are placed on the patient's head prior to image
      scanning.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7624657
TI  - Use of a frameless isocentric stereotactic system (NEURO-SAT) combined with the
      intraoperative microrecording.
AB  - Combining the frameless isocentric stereotactic system (NEURO-SAT) and
      intraoperative microrecording, we performed stereotactic biopsies of deep-seated
      brain tumors in two cases. Case 1 was a 58-year-old male suffering from a right
      thalamus to basal ganglia tumor and case 2 was a 29-year-old male suffering from
      brain stem tumor. In both cases, the border between the tumor and the normal
      tissue was ambiguous on neuroimagings. NEURO-SAT provides three-dimensional real
      time surgical navigation by displaying the positional information on the MRI
      images, and intraoperative microrecording shows a clear delineation between the
      tumor and the normal tissue in both cases. Therefore, since this combined method
      provides real-time surgical navigation and clear delineation of the tumor and
      normal tissue, it is a promising method of accurate and reliable image-directed
      stereotactic biopsy of deep-seated brain tumor.

PMID- 7624659
TI  - A stereotactic magnetic field digitizer.
AB  - A three-dimensional magnetic field digitizer has been interfaced the COMPASS
      Stereotactic System to act as a measuring device aiding in computer-assisted
      volumetric procedures. Reference points on the stereotactic headholder are used
      to create a transformation matrix to convert the digitizer coordinates to
      stereotactic coordinates, allowing the location of the stylus to be displayed on
      CT and reconstructed tumor volume images to maintain the surgeon's orientation.
      This technology is an adjunct to and employs treatment planning software of the
      system to calculate a target and determine a safe trajectory to a lesion.
      Environmental effects of the magnetic field have been studied to determine
      overall accuracy and reliability of the system. A device was developed to map the
      magnetic field in efforts to compensate for environmental effects. The device has
      been utilized on five procedures. We have found it to be a useful tool in aiding
      the surgeon in locating the surgical field preoperatively and maintaining
      orientation intraoperatively.

PMID- 7624660
TI  - Robot for CT-guided stereotactic neurosurgery.
AB  - At the 1989 meeting of the World Society for Stereotactic and Functional
      Neurosurgery in Maebashi, the authors presented the concept and design of a
      stereotactic neurosurgical robot. The first prototype has now been completed and
      has entered clinical testing. The characteristics are as follows. The robot is
      positioned behind the CT scan and operates inside the CT gantry. It is linked to
      the CT table and moves freely along its longitudinal axis, allowing for
      intraoperative scanning at any cranial level. The patient's body rests on the CT
      table, but the stereotactic headframe is fixed to the robot, allowing precise
      measurements of the head position under stereotactic conditions. During scanning,
      each CT slice appears immediately on the robotic workstation for selection of
      target and trajectory. In addition to the tool for automatic penetration of the
      skin, skull, and meninges, the robot is able to handle two other stereotactic
      instruments and to perform a complete stereotactic procedure without physical
      intervention by the physician. So far, depth electrodes and biopsy instruments
      have been developed for use by the robot. Since all parts of the robot were
      designed solely for stereotactic neurosurgery, integration of safety aspects was
      optimized. The first operations using an aspiration biopsy probe were
      successfully performed on 2 patients with malignant intracerebral cystic lesions
      on September 4, 1993.

PMID- 7624661
TI  - [Contribution of molecular and genetic biology in oncology].
AB  - During the last decades, major medical advances have been made in the
      understanding of cancer biology and led to the appearance of new diagnostic tools
      and development of innovative therapeutics. Some basic concepts in molecular
      medicine, oncogenes and tumour-suppressor genes are reviewed. Special topics are
      devoted to Ras, erbB2, p 53 and characteristical gene rearrangements, such as bcr
      abl, RARA-PML, VDJ, bcl2-IgH. The greater knowledge of the molecular etiology of
      cancer will contribute to disease screening, diagnosis, staging and therapy,
      detection of residual or recurrent disease, and development of new treatments,
      such as gene therapy or drugs targeted to oncogene products.

PMID- 7624663
TI  - [Molecular biology in the diagnosis of infectious diseases].
AB  - Since its introduction a decade ago, the polymerase chain reaction (PCR) has been
      largely utilized as a powerful research tool in microbiology. More recently, the
      simplification and the automatization of the PCR coupled with the recent
      development of several other nucleic amplification techniques has brought the
      introduction of molecular biology into the routine clinical laboratory. The PCR
      techniques offer new exciting perspectives in the field of microbiology in terms
      of clinical diagnosis and there are at least three areas in which this technology
      is expected to have a significant impact in the clinical microbiology laboratory
      over the next decade : 1) direct detection and identification of organisms that
      are slow-growing or those currently lacking a system for in vitro cultivation; 2)
      identification of genotypic markers of microbial resistance to specific
      antibiotics; 3) direct identification of microorganisms based upon amplification
      and sequence analysis of common sequence elements. This review also briefly
      discusses the various problems that must be overcome prior to routine use of PCR
      in the clinical laboratory.

PMID- 7624662
TI  - [Molecular diagnosis of hereditary diseases].
AB  - Molecular biology has produced important achievements in research, and provides
      useful applications to the clinical field. This is true today in diagnostics, and
      will be true in therapeutics tomorrow. The identification of pathogenic mutations
      through direct analysis of known genes allows diagnoses to be reached in a
      growing number of disorders. When mutations cannot be identified, familial
      linkage studies using polymorphic molecular markers will reach a diagnosis
      indirectly, most of the times. This is useful either presymptomatically or
      prenatally. The identification of genetic risk factors in targeted populations is
      becoming a means of prevention of multifactorial diseases. This approach opens a
      very large field of applications of molecular genetics in clinical practice.
      Basic concepts of molecular genetics are briefly reviewed, and the principles of
      diagnostics in hereditary diseases are approached via a few representative
      examples.

PMID- 7624665
TI  - [Acute appendicitis with foreign body].
AB  - An unusual presentation of acute appendicitis due to a foreign body is reported.
      The aetiology and physiopathology of appendicitis are discussed.

PMID- 7624664
TI  - [Diagnostic and/or prognostic value of the nuclear level determination of
      desoxyribonucleic acid (DNA) in nervous system tumors].
AB  - The diagnostic and prognostic value of the DNA ploidy level (nuclear DNA content)
      was studied in a series of 847 tumours of the nervous system. This series
      included 93 nerve sheath tumours, 224 meningiomas, 389 neuro-epithelial tissue
      tumours, 46 primitive neuroectodermal tumours (retinoblastomas, medulloblastomas,
      neuroblastomas, etc.) and 95 brain metastases. The DNA ploidy level determination
      was carried out by means of the computer-assisted microscope analysis (digital
      cell image analysis) of Feulgen-stained nuclei. The results show that the DNA
      ploidy level does not contribute significant diagnostic information when tumours
      are analyzed individually. Indeed, some tumours which are definitely benign like
      certain schwannomas and meningiomas can exhibit very high levels of aneuploidy,
      while some highly malignant tumours like certain glioblastomas and neuroblastomas
      can be diploid. In contrast to its weak diagnostic value, the DNA ploidy level
      appears to be a powerful prognostic factor with respect to the supratentorial
      astrocytic tumours of the adult. Indeed, patients with hypertriploid astrocytic
      tumours exhibit a survival period which is significantly longer when compared to
      that of patients with non-hypertriploid astrocytic tumours. These hypertriploid
      astrocytic tumours could be involved in a process of biological degeneration when
      reference is made to their proliferation activity which is significantly weaker
      than that of non-hypertriploid tumours.

PMID- 7624668
TI  - [Vocabulary of molecular biology].
AB  - The chemical basis of the genetic information and of his transmission has been
      well popularized in the early sixties, but it is only after 1970 that new
      techniques have permitted the modern knowledge in molecular biology; some
      applications are now available for the clinicians; the vocabulary of this
      knowledge is presented.

PMID- 7624667
TI  - [Urinary infections].

PMID- 7624666
TI  - [Cancer following treatment of Hodgkin disease].
AB  - The rate of long lasting complete remissions in Hodgkin's disease is high and
      relapses are rare. Complications after treatment of the disease may be either non
      oncologic or oncologic. The second cancers observed are acute leukaemias, non
      Hodgkin's lymphomas and solid tumors. Details are given about these complications
      and new strategies in the treatment modalities are now proposed according to the
      observed cancers.

PMID- 7624669
TI  - [How I explore... a patients with auricular fibrillation].

PMID- 7624670
TI  - [Clinical case of the month. Myocardial biopsy guided by transesophageal
      echography. Apropos of a case].

PMID- 7624672
TI  - [Surgical anatomy of the aortic valve. Relationship to the central fibrous body
      and conduction tissue].

PMID- 7624673
TI  - [Physiology of the mitral valve].

PMID- 7624671
TI  - [Infectious endocarditis. Current concepts].

PMID- 7624675
TI  - [Ischemic mitral valve insufficiency: principles of surgical treatment].

PMID- 7624674
TI  - [Carpentier's functional classification of mitral valve dysfunction].

PMID- 7624677
TI  - [Left ventricular outflow obstruction following surgical repair of the mitral
      valve].

PMID- 7624676
TI  - [Coarctation of the aortic isthmus (neonatal emergencies excepted)].

PMID- 7624678
TI  - [How I treat... a patient with auricular fibrillation (1)].

PMID- 7624679
TI  - [Complications of ostomies].

PMID- 7624680
TI  - [Consequences of ostomies].

PMID- 7624681
TI  - [Societies for stoma bearers].

PMID- 7624682
TI  - [Stoma therapy].

PMID- 7624683
TI  - [The stoma patient. Potential problems and expected solutions].

PMID- 7624684
TI  - [Acceptance of difficult patients. A collective strategy in psychosomatic
      perspective].

PMID- 7624685
TI  - [Total laryngectomy. Patient education].

PMID- 7624686
TI  - [The uterus and its adnexa. Gynecological laparoscopy].

PMID- 7624687
TI  - [Absolute isolation of the severely burned].

PMID- 7624689
TI  - [Digestive tract ostomies].

PMID- 7624688
TI  - [Foreword. Ostomy].

PMID- 7624690
TI  - [Urinary ostomies].

PMID- 7624692
TI  - [Mrs. Tomlison and GISSI nursing].

PMID- 7624691
TI  - [Italian group for the study of survival after infarct (GISSI) nursing.
      Evaluation of the perception of the quality of health of the patient with
      myocardial infarct. Final report of the study].

PMID- 7624693
TI  - [Methods and instruments of the research on the quality of life of myocardial
      infarct patients].

PMID- 7624695
TI  - [Lack of equality].

PMID- 7624694
TI  - [New facts in cardiology].

PMID- 7624696
TI  - [Lack of equality].

PMID- 7624697
TI  - [Gypsy children].

PMID- 7624698
TI  - [Evaluation of the quality of life and health of patients with myocardial
      infarct].

PMID- 7624699
TI  - Ethics in action. A young woman on the ICU with stage IV non-Hodgkin's lymphoma
      develops hepatorenal syndrome.

PMID- 7624700
TI  - Battered.

PMID- 7624701
TI  - Fight violence with forensic evidence.

PMID- 7624702
TI  - Start talking about testicular cancer.

PMID- 7624703
TI  - Turn ABGs into child's play.

PMID- 7624704
TI  - Giving meds through the tube.

PMID- 7624705
TI  - Complementary therapies. It's time to broaden our practice.

PMID- 7624706
TI  - More HIV patients may benefit from zalcitabine now.

PMID- 7624707
TI  - AIDS battle update: zidovudine okayed for pregnant women.

PMID- 7624708
TI  - Rx-to-OTC shift: not for these widely used drugs.

PMID- 7624709
TI  - Keep the family posted.

PMID- 7624710
TI  - The clock is running on RNs who won't change.

PMID- 7624711
TI  - A med/surg nurse's guide to mechanical ventilation.

PMID- 7624712
TI  - If ventilator patients could talk.

PMID- 7624713
TI  - Cardiovascular drugs. First-line therapy for CHF.

PMID- 7624714
TI  - What's wrong with this patient? Neuroleptic malignant syndrome.

PMID- 7624715
TI  - Nursing the family when a child dies.

PMID- 7624716
TI  - Fighting through an appeals process.

PMID- 7624717
TI  - Touch--of all kinds--is therapeutic.

PMID- 7624718
TI  - Whither unions?

PMID- 7624719
TI  - Finding the true source of a patient's allergic reaction.

PMID- 7624720
TI  - Codependency? Nonsense.

PMID- 7624722
TI  - Men in nursing.

PMID- 7624723
TI  - A stable approach to unstable angina.

PMID- 7624721
TI  - Ethics in action. A float nurse from the newborn nursery who has scant critical
      care experience.

PMID- 7624724
TI  - When insulin isn't enough.

PMID- 7624726
TI  - Nursing and peer support: a winning combination.

PMID- 7624725
TI  - Lung surgery: when less is more.

PMID- 7624727
TI  - Therapeutic touch and mastectomy: a case study.

PMID- 7624728
TI  - If you're fired.

PMID- 7624729
TI  - Back to high touch?

PMID- 7624730
TI  - Why the renal failure?

PMID- 7624731
TI  - Do I belong in nursing?

PMID- 7624732
TI  - Influence of ambient plasma noradrenaline on renal haemodynamics in type 1
      (insulin-dependent) diabetic patients and healthy subjects.
AB  - Imbalances in renal vasodilatory and vasoconstrictive mechanisms are responsible
      for the renal haemodynamic changes observed in Type 1 diabetes mellitus. Animal
      experiments have shown that noradrenaline (NA) infusion increases the
      intraglomerular pressure by predominantly efferent arteriolar vasoconstriction.
      The relationships between ambient plasma NA levels and renal haemodynamics were
      studied in 18 healthy control subjects (group C); in 17 normoalbuminuric diabetic
      patients (group D1) (albumin excretion rate (Ualb V) < 20 micrograms min-1), and
      in 17 microalbuminuric Type 1 diabetic patients (group D2) (UalbV 20-200
      micrograms min-1), all patients being without overt autonomic neuropathy. Supine
      glomerular filtration rate (GFR (ml min-1 1.73 m-2)) and effective renal plasma
      flow (ERPF (ml min-1 1.73 m-2)) were determined over a 2-h period using constant
      infusions of 125I-iothalamate and 131I-hippuran, respectively. The subjects were
      studied in the fasting state. The diabetic patients were investigated during near
      normoglycaemia. Data are given as means and SD. In group D1, GFR and ERPF (126 +/
      15 and 538 +/- 89, respectively) were elevated as compared with controls (108 +/
      15 and 478 +/- 73; p < 0.01 and p < 0.05, respectively). In group D2, GFR (124
      +/- 25, p < 0.05) but not ERPF (515 +/- 104) was higher than in the controls. GFR
      and ERPF were negatively correlated with venous plasma NA in group C (r = -0.61,
      p < 0.005 and r = -0.64, p < 0.001, respectively), in group D1 (r = -0.54, p <
      0.03 and r = -0.63, p < 0.005, respectively) and in group D2 (r = 0.53, p < 0.03
      and r = -0.60, p < 0.01, respectively). Multiple regression analysis disclosed
      that diabetes per se, independent from plasma NA, had a positive contribution to
      GFR. In contrast, ERPF was only related to plasma NA levels. GFR and ERPF are
      inversely related to venous plasma NA levels, both in healthy and in diabetic
      subjects, supporting the hypothesis that plasma NA is a vasoconstrictive
      substance. The independent positive effect of diabetes as a categorial variable
      on GFR, suggests that concomitant vasodilating mechanisms play a role in the
      renal haemodynamic alterations in Type 1 diabetes mellitus.

PMID- 7624733
TI  - In vitro reverse cholesterol transport from THP-1-derived macrophage-like cells
      with synthetic HDL particles consisting of proapolipoprotein A1 or apolipoprotein
      A1 and phosphatidylcholine.
AB  - The human monocytic leukaemia cell line THP-1 was induced to differentiate to
      macrophage-like cells by the addition of phorbol myristoyl acetate (PMA).
      Subsequently, the cells were enriched in cholesterol and these cholesterol laden
      cells were used to study the capability of reconstituted discoidal complexes
      (RDCs), consisting of either human apolipoprotein A1 (apo A1) or recombinant
      human proapolipoprotein A1 (proapo A1) and phosphatidylcholine (PC), to promote
      cholesterol efflux. RDCs containing apo A1 and proapo A1 were both effective in
      the mobilization of intracellular cholesterol, whether this was measured by
      intracellular cholesterol mass or by the appearance of radiolabelled cholesterol
      in the supernatant. Using the radiolabelling technique, the activity was
      saturable and followed Michaelis-Menten kinetics. For both types of complexes and
      for native HDL the maximum rate of cholesterol removed was approximately 0.5 nmol
      h-1 per 10(6) cells. For RDCs of proapo A1 and apo A1 and for native HDL the Km
      values were 3.7, 2.9 and 64.8 micrograms ml-1 respectively. A significant in
      vitro cholesterol efflux could only be achieved with protein-lipid complexes; no
      significant export was observed with either free proapo A1 or multilamellar PC
      liposomes without apolipoprotein. Both RDCs were found to be more active in the
      mobilization of intracellular cholesterol than HDL isolated from human plasma.
      The combined results demonstrate that synthetic complexes consisting either of
      apo A1 or proapo A1 and PC are both active in the in vitro reverse transport of
      cholesterol.

PMID- 7624734
TI  - Random capillary whole blood glucose test as a screening test for diabetes
      mellitus in a middle-aged population.
AB  - This study was aimed at assessing the adequacy of a random capillary whole blood
      glucose (RCBG) test as a screening test for diabetes mellitus in a middle-aged
      (55-year-old) Finnish population. Both the screening test (RCBG) and a standard 2
      h oral glucose tolerance test (OGTT) were performed on all the participants
      according to the WHO criteria. The prevalence based on the 2-h OGTTs was 8.5%
      (11.7% for men and 6.0% for women). The sensitivity, specificity and predictive
      values of the screening test for diabetes and the receiver operator
      characteristic (ROC) curves were studied. The likelihood ratios for diabetes
      within the test categories were also calculated. When a cut-off point of 6.2 mmol
      l-1 was used, which proved to be the most appropriate in the present study, the
      specificity was 92% and the sensitivity 63% (79% for men and 40% for women). The
      men had much higher sensitivities than the women at all cut-off points, but the
      specificities were comparable. The present study indicated that the RCBG test
      could be used as a screening test in a subpopulation with a high prevalence of
      diabetes and severe hyperglycaemia, but it would be quite insensitive in a
      subpopulation with a considerable overlap of RCBG values between the diabetic
      group and the non-diabetic one. It would be inappropriate to use the RCBG test as
      a routine screening test for diabetes in a general population, particularly among
      subjects with a known low prevalence of diabetes.

PMID- 7624735
TI  - Characterization and quantification of plasma proteins excreted in faeces from
      healthy humans.
AB  - Faecal plasma protein loss was studied in 38 healthy adults. Using crossed
      immunoelectrophoresis and single radial immunodiffusion the most frequently found
      proteins were alpha 1-antitrypsin, IgA, alpha 1-antichymotrypsin (found in 97,
      92, and 84% of subjects), prealbumin and IgM (both found in 55%). The major
      plasma proteins, albumin and IgG, were found in 37 and 13% of subjects,
      respectively, and in trace amounts only. alpha 2-macroglobulin could not be
      detected. There was no relation between the presence of proteins in faeces and
      their plasma concentration. When added to faeces, alpha 1-antitrypsin, alpha 1
      antichymotrypsin, and prealbumin were resistant to incubation (37 degrees C, 48
      h), whereas albumin, IgG, IgM, and IgA were rapidly degraded (within 8-24 h).
      Some IgA was bound to secretory component, indicating enteric secretion. alpha 2
      macroglobulin was semi-resistant to degradation, but its passage to the
      intestinal lumen may have been prevented by its molecular size. In conclusion,
      resistance to degradation, enteric secretion, and low molecular weight are the
      primary factors which favour the excretion of plasma proteins in faeces. The
      technique used in this study allows further studies in patients with inflammatory
      changes and protein-losing enteropathy.

PMID- 7624736
TI  - The effect of n-3 fatty acids on neutrophil chemiluminescence.
AB  - The effect of dietary supplementation with n-3 polyunsaturated fatty acids
      (PUFAs) on the production of free oxygen radicals from activated neutrophils was
      investigated in healthy subjects, using chemiluminescence. In the first study 22
      persons were give 4 g n-3 PUFAs daily for 6 weeks. There was a median reduction
      of chemiluminescence from neutrophils stimulated with opsonized zymosan of 37% (p
      < 0.001). The median content of eicosapentaenoic acid in platelets, used as an
      indicator for cellular fatty acid profile, increased from 0.70 to 2.80% (p <
      0.001), and there was a significant negative correlation between the
      chemiluminescence signal and the content of eicosapentaenoic acid in platelets (p
      < 0.001). In a second, low-dose study 24 persons were allocated to daily
      supplementation with either 0.65 g n-3 PUFAs or with a control oil for 6 weeks.
      Compared to the control group there was a median reduction of 38 and 44% in
      chemiluminescence from neutrophils stimulated with opsonized zymosan and
      phorbol,12-myristate,13-acetate (PMA), respectively. Neither of these
      differences, however, was statistically significant. These findings lend support
      for a possible role of n-3 PUFAs in the management of inflammatory disorders.

PMID- 7624737
TI  - Unchanged renal haemodynamics following high dose ascorbic acid administration in
      normoalbuminuric IDDM patients.
AB  - The object of the study was to test whether high dose ascorbic acid (AA) could
      normalize glomerular hyperfiltration in insulin-dependent diabetes mellitus
      (IDDM) patients. A prospective, double-blind, randomized, placebo (tartaric acid,
      TA) controlled study design was used, with parallel treatment lasting 4 weeks.
      Measurements were made before and after treatment, on 24 normoalbuminuric,
      normotensive male IDDM patients, who were randomized to ascorbic acid (n = 12,
      age 35 years (18-39), diabetes duration 12 years (2-12), BP 128/82 mmHg (SD
      14/6)), or to placebo (TA) (n = 12, age 30 years (19-36), diabetes duration 8
      years (2-17), BP 119/75 mmHg (SD 9/7). The intervention consisted of 6
      enterosoluble tablets of 500 mg AA or 213 mg TA, twice a day, being daily doses
      of 6 g AA or 2.55 g TA. No significant differences in any of the parameters
      measured were seen, when comparing results following AA or placebo treatment. The
      glomerular filtration rate (GFR, clearance of 125I-iothalamate) was unchanged
      while effective renal plasma flow (ERPF, clearance of 131I-hippuran) tended to
      decline in both groups. The GFRs before and after treatment in the AA-treated
      group were 141 (SD 15) and 134 (SD 12) ml min-1 1.73 m-2; NS (2p = 0.09). In the
      TA-treated group they were 142 (SD 19) and 137 (SD 16) ml min-1 1.73 m-2; NS (2p
      = 0.20). The ERPFs in the AA group were 584 (SD 93) and 545 (SD 47) ml min-1 1.73
      m-2; (2p = 0.06). In the TA group they were 618 (SD 108) and 574 (SD 98) ml min-1
      1.73 m-2 (2p = 0.03). The filtration fractions (FFs) in the AA group were 0.244
      and 0.246 NS.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7624738
TI  - Zinc heparin introduces a preanalytical error in the measurement of ionized
      calcium concentration.
AB  - In this study we determined how zinc heparin affected ionized calcium
      concentration determinations. Zinc heparin produced a positive bias (0.020-0.067
      mmol l-1) in ionized calcium measurement in serum/whole blood and a negative bias
      (-0.035 to -0.110 mmol l-1) with aqueous ionized calcium standards. To test if
      the positive bias was due to zinc ions displacing calcium from its protein
      calcium complexes, we reproduced the effect by adding ZnCl2 to pooled serum.
      Changes in [ZnCl2] (0.1-0.5 mmol l-1) caused a dose-dependent increase, a
      constant bias ([ZnCl2], 0.5-1.25 mmol l-1) or a dose-dependent decrease ([ZnCl2]
      > 1.25 mmol l-1) in ionized calcium concentration, independent of pH. Similar
      results were obtained when zinc concentration of the specimen was changed by
      varying the volume of blood collected into syringes containing zinc heparin. We
      conclude that zinc heparin produces a positive bias in ionized calcium
      measurement in protein-based matrices.

PMID- 7624739
TI  - Preconditioning by brief ischaemic episodes in the isolated rat heart assessed by
      31P NMR spectroscopy: dissociation between metabolic and functional recovery?
AB  - 31P NMR spectroscopy was used to investigate whether improved functional recovery
      in ischaemic preconditioning was due to improved metabolic recovery in isolated
      rat hearts. The preconditioning stimulus was global ischaemia of 1 or 4 min
      followed by 12 min of reperfusion (Langendorff mode). The hearts were then
      subjected to a main ischaemic period of 16 min and 40 min of reperfusion.
      Functional and metabolic recoveries of hearts were compared to a control group
      subjected only to the main ischaemia. Preconditioning improved recovery of
      contractile function during the final reperfusion. Thus left ventricular
      developed pressure (LVDP) and heart rate (HR) product after 40 min of reperfusion
      recovered to 56, 67 and 68% in the control group, 1 min group and 4 min group,
      respectively. However, the metabolic recovery was comparable in all groups. CrP
      and ATP recovered to levels of 67-78% (CrP) and 35-41% (ATP), and pH to a level
      of 7.13-7.15 (not different from baseline values) at the end of the final
      reperfusion. We conclude that the improved functional recovery in preconditioning
      is not due to a higher level of high energy phosphates or less acidosis during
      the final reperfusion.

PMID- 7624741
TI  - Granulocyte margination in bone marrow: comparison with margination in the spleen
      and liver.
AB  - The kinetics of radiolabelled granulocytes in the reticuloendothelial system were
      studied in order to evaluate granulocyte margination in bone marrow. A total of
      34 patients took part in a two-part study. In the first part, bone marrow uptake
      of indium-111-labelled granulocytes was retrospectively analysed in early (3-h)
      and late (24-h) images in 26 patients, 13 with bronchiectasis and 13 with
      enclosed abdominal abscesses. The ratios between early and late counts from the
      bone marrow, spleen, liver and inflammatory lesion were used to quantify
      granulocyte margination in bone marrow, postulating that if the lesion to bone
      marrow ratio at 24 h exceeds the value at 3 h, then the "excess" bone marrow
      counts on the early images would represent margination. In the second part, this
      suggestion was prospectively tested using Rutland-Patlak graphical and
      deconvolution analysis of dynamic data, acquired in 8 patients undergoing routine
      scanning with technetium-99m HMPAO-labelled granulocytes. In the first part of
      the study, it appeared that the bone marrow is a regional site of granulocyte
      margination, like the spleen, with at least one-half of the 3-h marrow signal
      arising from marginated granulocytes, compared with about two-thirds from the
      spleen. In the second part, it was found that the gradient of the Patlak plot,
      based on spleen and marrow, continuously decreased, consistent with bi
      directional movement of cells between these organs and the blood. Granulocyte
      pooling in the marrow was confirmed with deconvolution analysis, which generated
      biphasic retention functions for marrow and spleen. These curves were also
      consistent with two-way granulocyte exchange, and gave mean cell transit times in
      both organs of about 12 min and probabilities of extraction on each pass of 5
      10%. We conclude that granulocytes marginate in bone marrow to an extent similar
      to that in the spleen.

PMID- 7624740
TI  - Complement activation and release of tumour necrosis factor alpha, interleukin-2,
      interleukin-6 and soluble tumour necrosis factor and interleukin-2 receptors
      during and after cardiopulmonary bypass in children.
AB  - C3 activation products, terminal complement complex (TCC), and cytokines
      including interleukins 6 and 2 (IL-6, IL-2) and tumour necrosis factor-alpha
      (TNF), and the soluble IL-2 and TNF receptors were determined serially during and
      up to 48 h after open heart surgery in children. Significant increases were noted
      in soluble TNF and IL-2 receptor levels postoperatively (p < 0.05). No
      significant increase over preoperative levels was seen in the cytokines, except
      for IL-6 which was significantly increased postoperatively (p < 0.01), reaching a
      maximum 2 h postoperatively. C3 activation products and TCC levels increased
      significantly after weaning from cardiopulmonary bypass (p < 0.05). The IL-6
      response lagged behind the complement activation. We found a significant
      correlation between duration of cardiopulmonary bypass and IL-6 levels 48 h
      postoperatively (r = 0.852, p < 0.05). We conclude that the concentration of
      complement activation products, IL-6 and the soluble TNF and IL-2 receptors are
      significantly increased after open heart surgery in children. The cytokine
      receptor response probably reflects some sort of regulatory mechanism.

PMID- 7624742
TI  - [From research of non-suppressible serum insulin activity to the clinical
      application of recombinant insulin-like growth factor (rhIGF-I)].
AB  - The meandering and sometimes painful journey from the discovery of non
      suppressible insulin-like activity in serum to the chemical, biological and
      physiological characterization and biotechnological production of the two peptide
      hormones which are responsible for this plasma activity, i.e. IGF-I and IGF-II,
      is described. IGF-I is the major mediator of most activities of pituitary growth
      hormone and is therapeutically used for the stimulation of growth in growth
      hormone-insensitive (Laron) dwarfs and for the treatment of type A insulin
      resistant diabetics with non-functional insulin receptors. IGF-I and -II are not
      only endocrine hormones but also important locally produced peptides that act on
      cell differentiation during embryogenesis and on the regeneration of tissues
      during adult life via the autocrine/paracrine pathway. IGF research, chiefly in
      Zurich, serves as a basis on which to discuss more general aspects of the
      training of medical doctors and research structures in Switzerland.

PMID- 7624743
TI  - [Abnormalities of the atrial septum in adults: kind, prevalence and clinical
      relevance].
AB  - To classify interatrial septal anomalies in adults, 24,458 Doppler
      echocardiographic studies performed between 1. 1. 1987 and 31. 12. 1992 were
      reviewed. Patients below 16 years of age or with complex congenital heart
      disease, or after surgical closure of an atrial septal defect, were excluded.
      Additionally, all 823 transesophageal echocardiographies done between 1. 1. 1993
      and 31. 12. 1994 were analyzed to see whether a patent foramen ovale was present.
      Among 294 patients with interatrial septal anomalies (prevalence 1.2%;
      male:female = 1:1.4), 298 congenital anomalies of the interatrial septum were
      detected. 63% of interatrial septal anomalies constituted newly detected
      anomalies. Age ranged from 16 to 84 (median 43) years. In 21% of the patients the
      left-to-right shunt was > or = 50% (QP/QS > or = 2). In 25% pulmonary
      hypertension was present and 25% of the patients underwent surgery. A patent
      foramen ovale was present in 0.16% of all transthoracal and in 5.7% of all
      transesophageal echocardiographies. Secundum defects constituted 46%, atrial
      septal aneurysms 24%, patent foramen ovale 13%, atrioventricular canals 11%, and
      superior sinus venosus defects with anomalous pulmonary venous return 6% of all
      diagnoses. Associated anomalies were mitral valve prolapse in 14%, pulmonary
      valve stenosis in 3%, left-sided persistent vena cava superior and Chiari network
      in 2% each, anomalous pulmonary venous return, ventricular septal defect,
      bicuspid aortic valve, and Ebstein's anomaly in 1% each. 4% of the patients
      showed further cardiac lesions. CONCLUSIONS: Anomalies of the interatrial septum
      in adults were frequent and often newly detected. In a high percentage of
      patients with interatrial septum the left-to-right shunt was hemodynamically
      relevant.

PMID- 7624744
TI  - [Rhabdomyolysis in patients treated with simvastatin and cyclosporin: role of the
      hepatic cytochrome P450 enzyme system activity].
AB  - We describe two patients treated with a combination of cyclosporin and
      simvastatin who had to be hospitalized due to rhabdomyolysis. As suggested by
      reduced cyclosporin clearance, both patients had impaired activity of the hepatic
      cytochrome P450 enzyme system, which may have contributed to the development of
      rhabdomyolysis. After cessation of treatment with simvastatin and intensive
      hydration, both patients recovered within one week. While rhabdomyolysis has been
      described in several patients receiving the combination lovastatin/cyclosporin,
      so far only one case has been reported in patients treated with
      simvastatin/cyclosporin. Our cases therefore suggest that this complication may
      be more frequent than previously suspected. In patients treated with cyclosporin,
      HMG-CoA reductase inhibitors should be used cautiously, and concomitant
      administration of drugs inhibiting the hepatic cytochrome P450 enzyme system
      should be avoided.

PMID- 7624745
TI  - [Therapeutic management of patients with metastasized breast carcinoma].
AB  - In patients with metastasized breast cancer cure is beyond our therapeutic reach
      at present. In this situation the main treatment objectives are to improve
      existing or imminently threatening symptoms caused by the tumor growth, to retain
      or restore physical ability for as long as possible and, if possible, to prolong
      survival time. To achieve these treatment aims diphosphonates, hormones and
      cytotoxic mono- or polychemotherapy can be administered. The individualized
      administration of these drugs, adapted to the rate of the spread of metastases
      and tumor-induced symptoms, help to attain long survival without pronounced toxic
      side effects.

PMID- 7624747
TI  - [Neurological sequelae following exposure to thermo-oxidative degradation of
      polyurethane compounds].

PMID- 7624746
TI  - [Current aspects of therapy in chronic and acute leukemias].
AB  - A significant fraction of patients with chronic myelogenous leukemia (CML) in the
      chronic phase have durable hematologic remissions following treatment with
      interferon-alpha. Some clinical trials are beginning to show a modest overall
      survival advantage with interferon compared to hydroxyurea. The only curative
      therapy for CML is allogeneic bone marrow transplantation. In chronic lymphocytic
      leukemia (CLL), stable early stage disease requires no treatment. Recent trials
      have confirmed that several new purine analogues are effective in CLL. In acute
      myeloid leukemias there appears to be a dose-dependent effect on remission and
      intensified treatment may increase the percentage of disease free survivors.
      Hemopoietic growth factors may reduce treatment-related morbidity and mortality.
      Enhancement of cytotoxicity by prestimulation with GM-CSF is still controversial.
      All-trans retinoic acid induces remissions in 80% of patients with acute
      promyelocytic leukemia by forcing the leukemic promyelocytes to maturation.
      Allogeneic bone marrow transplantation is effective in high risk patients with
      Philadelphia chromosome positive acute lymphocytic leukemia (ALL), in patients
      with relapse or resistant acute myelogenous leukemia (AML) or ALL. In patients
      with ALL a risk-adapted therapy including allogeneic and autologous bone marrow
      transplantation and the use of hemopoietic growth factors to improve supportive
      therapy may result in more cures.

PMID- 7624748
TI  - [Scientific raisins from SMW (Swiss Medical Weekly). Insulin action in psychotic
      agitation states. 1932].

PMID- 7624749
TI  - [Scientific raisins from 125 years SMW (Swiss Medical Weekly). Clinical
      demonstrations from the Zurich dermatology clinic. 1926].

PMID- 7624750
TI  - Managing care starts with partnership.

PMID- 7624751
TI  - Defining assessment parameters in dual injuries: spinal cord injury and traumatic
      brain injury.
AB  - Assessment parameters for muscle testing in the individual with a spinal cord
      injury (SCI) have been clearly defined by the American Spinal Injury Association
      (ASIA). However, the ASIA standard requires the individual's participation in
      reporting sensory information and he/she must be able to perform specific tasks
      to complete the examination. In an individual with a dual injury, a SCI and a
      traumatic brain injury (TBI), neurological assessment can be impeded by the
      individual's inability to participate in the exam. Assessment needs to
      incorporate both cognitive and physical parameters that will appropriately assess
      both injuries. This article reviews the assessment parameters for both spinal
      cord injury and traumatic brain injury and provides assessment guidelines for
      bedside evaluation of functional ability. In addition, a review of the
      biomechanics of injury will provide a model for understanding dual injury.

PMID- 7624752
TI  - Self-care competence among persons with spinal cord injury.
AB  - The authors of this article report the results of a secondary data analysis which
      examined the self-care competence of persons with spinal cord injury (SCI) and
      the retention of cognitive and functional skills following discharge from acute
      rehabilitation as well as additional learning of self-care following discharge.
      The sample consisted of 48 persons with SCI from two Veterans Affairs Medical
      Centers and a state university affiliated rehabilitation program. The data
      collection tool was the Self-Care Assessment Tool (SCAT) which measures cognitive
      and functional skills in eight self-care areas: bathing/grooming, nutritional
      management, taking medications, mobility/transfer/safety, skin management,
      bladder management, bowel management, and dressing. The overall self-care
      competence of the participants was high (mean = 78.25) as was their competence in
      the eight self-care areas. In general, participants retained both the cognitive
      information and functional skills learned in the acute rehabilitation setting and
      also continued to learn after discharge in both cognitive information and
      functional skills.

PMID- 7624753
TI  - Can your research subjects read your study's informed consent form?

PMID- 7624754
TI  - Wheelchair sports and the disabled athlete.

PMID- 7624755
TI  - Product evaluation is an integral part of the patient care environment.

PMID- 7624756
TI  - [Current status of transcranial color duplex ultrasound in the adult].
AB  - Technical improvements accomplished over the last few years allow imaging of
      intracranial parenchymal structures as well as of basal cerebral arteries by
      ultrasound. Low frequency probes (2-2.5 MHz) and colour Doppler technology are
      required for these examinations. Recent experience in clinical practice proves
      that perfusion patterns in basal cerebral arteries can be depicted more
      accurately and with better reproducibility compared to conventional transcranial
      Doppler sonography. Simultaneous B-Mode imaging allows detection of cerebral
      haemorrhage, brain tumours and ventricular enlargement. Preliminary data on the
      sensitivity and specificity are promising and encourage further prospective
      studies.

PMID- 7624757
TI  - [Transcranial Doppler ultrasound: effects of intravenous anesthetics in
      neurosurgical patients].
AB  - AIM: Although adverse effects on cerebral blood flow have been reported,
      intravenous anaesthetic and sedative agents are often used in neurosurgical
      patients. Monitoring of these effects by transcranial Doppler sonography remains
      a questionable procedure as long as the cross-sectional area of the insonated
      basal cerebral arteries is unknown. This study should evaluate the effects of
      thiopental, propofol, midazolam and alfentanil on flow velocities and "vessel
      cross-sectional area" (proportional to the reflected Doppler signal power)
      measured by transcranial Doppler sonography. METHOD: 19 patients with severe
      cerebral lesions (Glasgow Coma Scale < 6) were investigated. They were
      hyperventilated and sedated with fentanyl and flunitrazepam. The Doppler probe
      was fixed to the temporal bone and focussed to the middle cerebral artery of the
      more severely lesioned side. Baseline values of flow velocities and vascular
      cross-sectional area were measured. If routine nursing procedures required a
      deeper degree of sedation, either thiopental 2.5 mg/kg, propofol 1 mg/kg,
      midazolam 0.075 mg/kg or alfentanil 0.025 mg/kg were injected intravenously over
      30 s. Further measurements were made 60, 120 and 300 s after start of the
      injection. Mean +/- SD were calculated, statistical evaluation was performed by
      analysis of variance and paired t-tests using the Bonferroni correction (p <
      0.05). RESULTS: The injected agents induced significant decreases of the mean
      value of flow velocities; the "vessel cross-sectional area" remained unaltered.
      In some patients paradoxical increases of v were observed. CONCLUSION: The
      results indicate that intravenous anaesthetic agents are not likely to influence
      the cross-sectional area of the major basal cerebral arteries. Therefore TCD
      seems to be a valid tool to monitor the effects of these agents on the cerebral
      circulation of neurosurgical patients. This is probably of prognostic and
      therapeutic value.

PMID- 7624759
TI  - [Concomitant hemodynamic effects of intracoronary injections of a new
      transpulmonary contrast medium].
AB  - AIM: A new transpulmonary echo contrast agent (SH U 508) was injected
      intracoronally to six anaesthetised sheep to examine its possible direct cardiac
      effects. METHOD: SH U 508 was injected in randomised order in three different
      volumes (2, 4 and 8 ml; n = 12, 10, 9) with the same drug concentration of 200
      mg/ml. RESULTS: The 2 ml and 4 ml injections had no relevant effect on the
      arterial, pulmonary-arterial and ventricular pressures, on the left ventricular
      contraction velocity and on the myocardial blood flow (less than +/- 10% of the
      control value). The left ventricular relaxation velocity decreased by 20%. The
      disturbance of the left ventricular relaxation at a volume of 8 ml was pronounced
      (about 40% decrease). Slight left ventricular dysfunction further manifested
      itself in a decreased systolic pressure (-15%) and increased left ventricular
      enddiastolic pressure (20%). CONCLUSION: In summary the overall effect of the
      intracoronary injections of SH U 508 exhibited only minor cardiac side effects.
      If the current results are extrapolated to peripheral-venous application, the
      clinically required central-venous 8 ml injection of a 400 mg/ml suspension is
      not expected to produce any coronary haemodynamic side effects, due to drug
      dilution in the pulmonary circulation and resulting low intra-coronary
      concentrations.

PMID- 7624758
TI  - [Transcranial color-coded real time ultrasound. An improvement in patient
      monitoring in the neurosurgical intensive care unit?].
AB  - It is still not always possible to detect in time early intracranial
      complications in neurosurgical critical care patients. In addition, the exact
      definition of the lesion requires an often life-threatening transport to the CCT.
      Hence, there is still a need for improved bedside monitoring. New developments in
      ultrasound technique enable us not only to get a two-dimensional image of
      intracranial parenchymatous structures through the intact bone but also to
      visualise, by means of colour-coding, the blood flow the intracranial vessels. In
      70 mostly neurotraumatised patients we found that this method is helpful in
      solving diagnostic or therapeutic problems without the patient having to leave
      the intensive care unit.

PMID- 7624760
TI  - [Evaluating the extracranial cerebral arteries with ultrasound angiography].
AB  - AIM: Ultrasound angiography is a new method of colour-coded vessel imaging. The
      present study aimed at giving further information on its clinical utility in
      neurosonology. METHOD: The extracranial arteries of 53 patients and 5 normal
      persons were investigated by ultrasound angiography in comparison with colour
      coded duplex sonography. RESULTS: We found a sharper imaging of stenoses and
      plaques by ultrasound angiography compared with colour Doppler. The imaging of
      the vessels can be achieved more continuously, avoiding dropouts of the colour.
      Small vessels and branches can be detected more reality. CONCLUSION: Ultrasound
      angiography represents a valuable additional imaging technique to colour-coded
      duplex sonography, providing further information, especially with regard to the
      border of plaques and stenoses.

PMID- 7624761
TI  - [Effect of muscular work on the myosonogram].
AB  - AIM: The purpose of this study was to examine quantitatively the change of muscle
      thickness and echo intensity caused by muscle exercise in healthy persons.
      METHOD: 16 healthy volunteers (7 women, 9 men), aged 23 to 37 years, underwent
      static exercises of the rectus abdominis, rectus femoris/vastus intermedius, and
      tibialis anterior muscles. In addition, the rectus femoris/vastus intermedius
      muscles were exercised dynamically. Thicknesses of these muscles were measured
      before and during/after exercise using the electronic caliper and computer
      assisted gray-scale analysis of the echo signals. RESULTS: Short, maximal
      isometric contraction resulted in an increase of thickness by 5 to 18% depending
      on the examined muscle (p < 0.01). The echo intensity of the rectus femoris and
      vastus intermedius muscles decreased significantly (-8% and -26%, p < 0.01). The
      increase of muscle thickness immediately after isometric exercise for up to 90 s
      was significantly correlated to the duration of contraction (r = 0.26 to 0.49, p
      < 0.05). Muscle echo intensities did not significantly correlate with the
      duration of the contraction. After dynamic exercise on a bicycle ergometer both
      thickness of the rectus femoris/vastus intermedius muscles (+12.5%, p < 0.01) and
      echo intensity of the vastus intermedius muscle increased (+19.5%, p < 0.01). The
      change of echo intensity of the vastus intermedius muscle after static and
      dynamic exercise was significantly different (-26% vs. +18%, p < 0.001).
      CONCLUSION: Muscle thickness increases during and after static as well as dynamic
      exercise. Echo intensity may be unchanged, decreased or increased, depending on
      the exercised muscle and mode of exercise.

PMID- 7624762
TI  - [Prevalence of goiter in the Aachen area. Ultrasound volumetry of the thyroid
      gland of 1,336 adults in an endemic goiter region].
AB  - AIM: The aim of the study was to assess the prevalence of thyroid enlargement by
      ultrasonic volume measurements. RESULTS: 1336 adults living in the iodine
      deficient area of Aachen, West Germany (760 females, 576 males, mean age: 54.05
      +/- 16.09 years) were included in the investigation. The ultrasonic examination
      was carried out in patients who did not suffer from thyroid disease at the time
      of study. RESULTS: The thyroid volume was age-dependent and varied from 13.3 +/-
      10.4 ml in patients < 21 years to 29.9 +/- 24.3 ml in patients > 70 years. The
      prevalence of thyroid enlargement ranged from 14.3% in young people to 51.3% in
      the elderly. There was no difference in the volumes of the left and right thyroid
      lobe. The prevalence of thyroid enlargement was higher in females compared to
      males (p < 0.05). Retrosternal thyroid mass was detected in 25% of all patients >
      70 years. CONCLUSION: There is evidence of a high prevalence of thyroid
      enlargement in iodine-deficient areas.

PMID- 7624764
TI  - Gaining perspective.

PMID- 7624763
TI  - [The value of fine needle puncture in adrenal gland tumors].
AB  - The value of fine needle biopsy (FNB) in adrenal masses was investigated in 33
      patients presenting with such masses. Representative material was obtained 18
      times from 19 patients with a history of tumour. 4 of them were diagnosed to be
      genuinely benign and 14 to be genuinely malignant. Further representative
      material was obtained 13 times from 14 patients with incidental findings of
      adrenal masses. The material gained by puncturing was classified correctly as
      benign in 9 cases, and twice it was considered benign although the tumours later
      proved malignant. In one case a clinically not suspected malignant lesion was
      detected by FNB, while in another case a malignant lesion was suspected by FNB,
      whereas a benign tumour was proven by means of surgery. The share of malignant
      diagnoses corresponded with the size of tumour, ascertained by the application of
      ultrasound or CT. The rate of malignant adrenal masses, which were found
      incidentally, increased from 7 cm onwards; however, the rate of malignant adrenal
      masses obtained from patients with a history of tumour increased distinctively
      already from 4 cm onwards. From 11 patients out of 33, adrenal tissue was
      obtained and classified as benign lesion (adenoma), although, by means of FNB and
      the conditions for reasons of method, a well differentiated carcinoma cannot be
      excluded. CONCLUSION: FNB is indicated for non-functioning tumours examined in
      patients with a history of tumour, furthermore, for incidental findings of the
      size between 4-6 cm. A diagnostic approach to adrenal masses is suggested.

PMID- 7624765
TI  - Botulinum toxin--a therapy for dystonia.

PMID- 7624766
TI  - Antimicrobial resistance: controlling the problem.

PMID- 7624767
TI  - Bacterial genome sequence bagged.

PMID- 7624768
TI  - R&D budget takes shape in Congress, piece by piece. NIH: the view from the
      Senate.

PMID- 7624769
TI  - "Obese" protein slims mice.

PMID- 7624770
TI  - New foot steps into walking debate.

PMID- 7624771
TI  - In Toulouse, the weather--and the science--are hot.

PMID- 7624772
TI  - Sterkfontein member 2 foot bones of the oldest South African hominid.
AB  - Four articulating hominid foot bones have been recovered from Sterkfontein Member
      2, near Johannesburg, South Africa. They have human features in the hindfoot and
      strikingly apelike traits in the forefoot. While the foot is manifestly adapted
      for bipedalism, its most remarkable characteristic is that the great toe (hallux)
      is appreciably medially diverged (varus) and strongly mobile, as in apes.
      Possibly as old as 3.5 million years, the foot provides the first evidence that
      bipedal hominids were in southern Africa more than 3.0 million years ago. The
      bones probably belonged to an early member of Australopithecus africanus or
      another early hominid species.

PMID- 7624773
TI  - Importance of historical contingency in the stereochemistry of hydratase
      dehydratase enzymes.
AB  - There are two stereochemical classes of hydratase-dehydratase enzymes. Those that
      catalyze the addition of water to alpha, beta-unsaturated thioesters give syn
      addition-elimination stereochemistry, whereas those that catalyze the addition of
      water to conjugated carboxylate substrates give anti stereochemistry. This
      dichotomy could reflect different adaptive advantages or contingencies of
      separate evolutionary histories. Determination of the nonenzymatic
      stereochemistry of deuterium oxide addition to fumarate and to S-crotonyl N
      acetylcysteamine has provided direct evidence for the importance of the
      contingencies of evolutionary history, rather than chemical efficiency, in the
      pathways of these hydratase-dehydratase enzymes.

PMID- 7624774
TI  - Interaction of papillomavirus E6 oncoproteins with a putative calcium-binding
      protein.
AB  - Human papillomaviruses (HPVs) are associated with the majority of cervical
      cancers and encode a transforming protein, E6, that interacts with the tumor
      suppressor protein p53. Because E6 has p53-independent transforming activity, the
      yeast two-hybrid system was used to search for other E6-binding proteins. One
      such protein, E6BP, interacted with cancer-associated HPV E6 and with bovine
      papillomavirus type 1 (BPV-1) E6. The transforming activity of BPV-1 E6 mutants
      correlated with their E6BP-binding ability. E6BP is identical to a putative
      calcium-binding protein, ERC-55, that appears to be localized in the endoplasmic
      reticulum.

PMID- 7624775
TI  - Unimpaired thymic and peripheral T cell death in mice lacking the nuclear
      receptor NGFI-B (Nur77).
AB  - T cell hybridomas require the immediate-early gene NGFI-B (nur77) for T cell
      receptor (TCR)-mediated apoptosis, a model for negative selection of self
      reactive T cells. TCR-mediated death was examined in mice bearing an NGFI-B loss
      of-function mutation, either by administration of antibodies to CD3 (anti-CD3) or
      in two well-characterized transgenic models expressing self-reactive TCRs. Both
      the extent and the rate of thymocyte death were unimpaired. Anti-CD3-induced
      death was normal in CD4+ peripheral T cells, in which death is mediated
      predominantly by the Fas signaling pathway. Thus, no unique requirement for NGFI
      B is observed for thymic or peripheral T cell death.

PMID- 7624776
TI  - Effects of the obese gene product on body weight regulation in ob/ob mice.
AB  - C57BL/6J mice with a mutation in the obese (ob) gene are obese, diabetic, and
      exhibit reduced activity, metabolism, and body temperature. Daily intraperitoneal
      injection of these mice with recombinant OB protein lowered their body weight,
      percent body fat, food intake, and serum concentrations of glucose and insulin.
      In addition, metabolic rate, body temperature, and activity levels were increased
      by this treatment. None of these parameters was altered beyond the level observed
      in lean controls, suggesting that the OB protein normalized the metabolic status
      of the ob/ob mice. Lean animals injected with OB protein maintained a smaller
      weight loss throughout the 28-day study and showed no changes in any of the
      metabolic parameters. These data suggest that the OB protein regulates body
      weight and fat deposition through effects on metabolism and appetite.

PMID- 7624777
TI  - Weight-reducing effects of the plasma protein encoded by the obese gene.
AB  - The gene product of the ob locus is important in the regulation of body weight.
      The ob product was shown to be present as a 16-kilodalton protein in mouse and
      human plasma but was undetectable in plasma from C57BL/6J ob/ob mice. Plasma
      levels of this protein were increased in diabetic (db) mice, a mutant thought to
      be resistant to the effects of ob. Daily intraperitoneal injections of either
      mouse or human recombinant OB protein reduced the body weight of ob/ob mice by 30
      percent after 2 weeks of treatment with no apparent toxicity but had no effect on
      db/db mice. The protein reduced food intake and increased energy expenditure in
      ob/ob mice. Injections of wild-type mice twice daily with the mouse protein
      resulted in a sustained 12 percent weight loss, decreased food intake, and a
      reduction of body fat from 12.2 to 0.7 percent. These data suggest that the OB
      protein serves an endocrine function to regulate body fat stores.

PMID- 7624778
TI  - Recombinant mouse OB protein: evidence for a peripheral signal linking adiposity
      and central neural networks.
AB  - The recent positional cloning of the mouse ob gene and its human homology has
      provided the basis to investigate the potential role of the ob gene product in
      body weight regulation. A biologically active form of recombinant mouse OB
      protein was overexpressed and purified to near homogeneity from a bacterial
      expression system. Peripheral and central administration of microgram doses of OB
      protein reduced food intake and body weight of ob/ob and diet-induced obese mice
      but not in db/db obese mice. The behavioral effects after brain administration
      suggest that OB protein can act directly on neuronal networks that control
      feeding and energy balance.

PMID- 7624779
TI  - Induction of MHC class I genes in neurons.
AB  - Whether neurons express major histocompatibility complex (MHC) class I genes has
      not been firmly established. The techniques of confocal laser microscopy, patch
      clamp electrophysiology, and reverse transcriptase-polymerase chain reaction were
      combined here to directly examine the inducibility of MHC class I genes in
      individual cultured rat hippocampal neurons. Transcription of MHC class I genes
      was very rare in neurons with spontaneous action potentials. In electrically
      silent neurons, transcription was noted, with expression of beta 2-microglobulin
      under tighter control than in class I heavy chain molecules. Surface expression
      of class I molecules occurred only in electrically silent neurons treated with
      interferon gamma. Immunosurveillance by cytotoxic T cells may be focused on
      functionally impaired neurons.

PMID- 7624780
TI  - Monitoring release of neurotrophic activity in the brains of awake rats.
AB  - Intracerebral microdialysis of awake rats was used to monitor the possible
      release of neurotrophic factors from brain cells in response to injury and
      excitation. Perfusates were tested with ganglia bioassays and enzyme immunoassay.
      Trophic activity was released after implantation of the microdialysis probe into
      the hippocampus but not into the striatum, as assessed by increased nerve fiber
      outgrowth from Remak's ganglion. Kainic acid treatment significantly increased
      the release of trophic activity from hippocampal sites. These findings suggest
      that the brain responds to mechanical injury as well as to certain excitatory
      stimuli by regional extracellular release of neurotrophic activity that is not
      identical to the actions of known neurotrophic factors.

PMID- 7624782
TI  - "Wired" science or whither the printed page?

PMID- 7624781
TI  - Activation of yeast PBS2 MAPKK by MAPKKKs or by binding of an SH3-containing
      osmosensor.
AB  - The role of mitogen-activated protein (MAP) kinase cascades in integrating
      distinct upstream signals was studied in yeast. Mutants that were not able to
      activate PBS2 MAP kinase kinase (MAPKK; Pbs2p) at high osmolarity were
      characterized. Pbs2p was activated by two independent signals that emanated from
      distinct cell-surface osmosensors. Pbs2p was activated by MAP kinase kinase
      kinases (MAPKKKs) Ssk2p and Ssk22p that are under the control of the SLN1-SSK1
      two-component osmosensor. Alternatively, Pbs2p was activated by a mechanism that
      involves the binding of its amino terminal proline-rich motif to the Src homology
      3 (SH3) domain of a putative transmembrane osmosensor Sho1p.

PMID- 7624783
TI  - Mass extinctions and periodicity.

PMID- 7624784
TI  - FDA antibody rules.

PMID- 7624785
TI  - FDA antibody rules.

PMID- 7624787
TI  - "Fat hormone" poses hefty problem for journal embargo.

PMID- 7624786
TI  - Bringing AZT to poor countries.

PMID- 7624788
TI  - Europe opens institute to deal with gene data deluge.

PMID- 7624789
TI  - A new twist to the cell cycle.

PMID- 7624790
TI  - Knocking genes in instead of out.

PMID- 7624791
TI  - AIDS from vaccine?

PMID- 7624792
TI  - Genetic networks.

PMID- 7624793
TI  - Circuit simulation of genetic networks.
AB  - Genetic networks with tens to hundreds of genes are difficult to analyze with
      currently available techniques. Because of the many parallels in the function of
      these biochemically based genetic circuits and electrical circuits, a hybrid
      modeling approach is proposed that integrates conventional biochemical kinetic
      modeling within the framework of a circuit simulation. The circuit diagram of the
      bacteriophage lambda lysislysogeny decision circuit represents connectivity in
      signal paths of the biochemical components. A key feature of the lambda genetic
      circuit is that operons function as active integrated logic components and
      introduce signal time delays essential for the in vivo behavior of phage lambda.

PMID- 7624794
TI  - Structure of Bam HI endonuclease bound to DNA: partial folding and unfolding on
      DNA binding.
AB  - The crystal structure of restriction endonuclease Bam HI complexed to DNA has
      been determined at 2.2 angstrom resolution. The DNA binds in the cleft and
      retains a B-DNA type of conformation. The enzyme, however, undergoes a series of
      conformational changes, including rotation of subunits and folding of disordered
      regions. The most striking conformational change is the unraveling of carboxyl
      terminal alpha helices to form partially disordered "arms." The arm from one
      subunit fits into the minor groove while the arm from the symmetry related
      subunit follows the DNA sugar-phosphate backbone. Recognition of DNA base pairs
      occurs primarily in the major groove, with a few interactions occurring in the
      minor groove. Tightly bound water molecules play an equally important role as
      side chain and main chain atoms in the recognition of base pairs. The complex
      also provides new insights into the mechanism by which the enzyme catalyzes the
      hydrolysis of DNA phosphodiester groups.

PMID- 7624795
TI  - Fabrication of submicrometer features on curved substrates by microcontact
      printing.
AB  - Microcontact printing (mu CP) has been used to produce patterned self-assembled
      monolayers (SAMs) with submicrometer features on curved substrates with radii of
      curvature as small as 25 micrometers. Wet-chemical etching that uses the
      patterned SAMs as resists transfers the patterns formed by mu CP into gold. At
      present, there is no comparable method for microfabrication on curved surfaces.

PMID- 7624796
TI  - Detection of creatinine by a designed receptor.
AB  - An artificial receptor has been designed to bind creatinine with a color change
      (chromogenic response) caused by proton transfer from one end of the receptor to
      the other. The receptor was synthesized and found to extract creatinine from
      water into chlorocarbon solvents. The color change in the organic layer is
      specific for creatinine relative to other organic solutes, and it is selective
      for creatinine relative to sodium, potassium, and ammonium ions. The chromogenic
      mechanism is revealed by x-ray crystal structures of creatinine, the free
      receptor, and the complex, showing "induced fit" binding resulting from
      electronic complementarity between host and guest.

PMID- 7624797
TI  - Rescue of the En-1 mutant phenotype by replacement of En-1 with En-2.
AB  - The related mouse Engrailed genes En-1 and En-2 are expressed from the one- and
      approximately five-somite stages, respectively, in a similar presumptive mid
      hindbrain domain. However, mutations in En-1 and En-2 produce different
      phenotypes. En-1 mutant mice die at birth with a large mid-hindbrain deletion,
      whereas En-2 mutants are viable, with cerebellar defects. To determine whether
      these contrasting phenotypes reflect differences in temporal expression or
      biochemical activity of the En proteins, En-1 coding sequences were replaced with
      En-2 sequences by gene targeting. This rescued all En-1 mutant defects,
      demonstrating that the difference between En-1 and En-2 stems from their
      divergent expression patterns.

PMID- 7624798
TI  - Role of the ubiquitin-proteasome pathway in regulating abundance of the cyclin
      dependent kinase inhibitor p27.
AB  - The p27 mammalian cell cycle protein is an inhibitor of cyclin-dependent kinases.
      Both in vivo and in vitro, p27 was found to be degraded by the ubiquitin
      proteasome pathway. The human ubiquitin-conjugating enzymes Ubc2 and Ubc3 were
      specifically involved in the ubiquitination of p27. Compared with proliferating
      cells, quiescent cells exhibited a smaller amount of p27 ubiquitinating activity,
      which accounted for the marked increase of p27 half-life measured in these cells.
      Thus, the abundance of p27 in cells is regulated by degradation. The specific
      proteolysis of p27 may represent a mechanism for regulating the activity of
      cyclin-dependent kinases.

PMID- 7624799
TI  - Cloning and characterization of a G protein-activated human phosphoinositide-3
      kinase.
AB  - Phosphoinositide-3 kinase activity is implicated in diverse cellular responses
      triggered by mammalian cell surface receptors and in the regulation of protein
      sorting in yeast. Receptors with intrinsic and associated tyrosine kinase
      activity recruit heterodimeric phosphoinositide-3 kinases that consist of p110
      catalytic subunits and p85 adaptor molecules containing Src homology 2 (SH2)
      domains. A phosphoinositide-3 kinase isotype, p110 gamma, was cloned and
      characterized. The p110 gamma enzyme was activated in vitro by both the alpha and
      beta gamma subunits of heterotrimeric guanosine triphosphate (GTP)-binding
      proteins (G proteins) and did not interact with p85. A potential pleckstrin
      homology domain is located near its amino terminus. The p110 gamma isotype may
      link signaling through G protein-coupled receptors to the generation of
      phosphoinositide second messengers phosphorylated in the D-3 position.

PMID- 7624800
TI  - A gene outside the human MHC related to classical HLA class I genes.
AB  - By presenting antigenic peptides to T lymphocytes, major histocompatibility
      complex (MHC) class I molecules play important roles in the human immune system.
      Knowledge is limited on the evolutionary history of human MHC class I-related
      molecules. An expressed class I gene, MR1, has now been identified on human
      chromosome 1q25, outside the MHC. In contrast to other known human divergent
      class I genes, MR1 encodes peptide-binding domains similar to those encoded by
      human leukocyte antigen (HLA) class I genes on chromosome 6 and by nonmammalian
      classical MHC class I genes. This gene may thus contribute to understanding the
      evolution of the MHC.

PMID- 7624801
TI  - Excision of deoxyribose phosphate residues by DNA polymerase beta during DNA
      repair.
AB  - Eukaryotic DNA polymerase beta (pol beta) can catalyze DNA synthesis during base
      excision DNA repair. It is shown here that pol beta also catalyzes release of 5'
      terminal deoxyribose phosphate (dRP) residues from incised apurinic-apyrimidinic
      sites, which are common intermediate products in base excision repair. The
      catalytic domain for this activity resides within an amino-terminal 8-kilodalton
      fragment of pol beta, which comprises a distinct structural domain of the enzyme.
      Magnesium is required for the release of dRP from double-stranded DNA but not
      from a single-stranded oligonucleotide. Analysis of the released products
      indicates that the excision reaction occurs by beta-elimination rather than
      hydrolysis.

PMID- 7624802
TI  - Motor cortical activity in a context-recall task.
AB  - A monkey was trained to respond on the basis of the serial position of a test
      stimulus in a sequence. First, three stimuli were presented successively on a
      circle. Then one of them (except the last) changed color (test stimulus) and
      served as the go signal: The monkey was required to produce a motor response in
      the direction of the stimulus that followed the test stimulus. When the test
      stimulus was the second in the sequence, there was a change in motor cortical
      activity from a pattern reflecting the direction of this stimulus to the pattern
      associated with the direction of the motor response. This change was abrupt,
      occurred 100 to 150 milliseconds after the go signal, and was evident both in the
      activity of single cells and in the time-varying neuronal population vector.
      These findings identify the neural correlates of a switching process that is
      different from a mental rotation described previously.

PMID- 7624804
TI  - Juvenile offenders, with special reference to sex differences.
AB  - Social and demographic background variables relevant to male and female juvenile
      offenders were studied prospectively in a geographically defined population of
      6,007 males and 5,757 females in Northern Finland, together with the distribution
      of offences by type and number between the sexes. Up to the age of 25 years, 532
      males (8.9%) and 60 females (1.0%) had committed at least one crime leading to a
      criminal record. An intelligence quotient (IQ) of 50-84, but not below 50, was
      most closely associated with delinquency, as was school performance, in that not
      only was poor attainment associated with an increased incidence of delinquency,
      but above-average attainment was also predictive of a lower incidence. This is
      not interpreted as a causal association but rather an indication of similarity
      between the demands of the educational system and demands regarding socially
      desirable behaviour. The demographic, social, educational and health factors
      predictive of delinquency were very similar for males and females, and the
      reasons for the difference in the incidence of delinquency between the sexes must
      be looked for among the general differences in cultural demands and biological
      factors.

PMID- 7624803
TI  - Characteristics of youth suicide in Hong Kong.
AB  - This paper explores the intrapersonal and sociocultural factors behind youth
      suicide in Hong Kong. The coroner's court reports of consecutive population-based
      youth suicide (below age of 25 years, n = 303) cases from 1986 to 1992 were
      reviewed. Compared with other countries, Hong Kong had low male but high female
      youth suicide rates. The number of undetermined deaths did not significantly
      affect the estimated suicide rates. Cross-cultural differences in youth suicide
      rates may be understood from a differential distribution of risk factors and
      cultural attitudes towards role behaviours and suicide. Youth suicides in Hong
      Kong were characterised by a high prevalence of psychiatric disturbances and age
      normative precipitants; both findings bear great resemblances to samples studied
      elsewhere. The results were evaluated in light of studies in different
      sociocultural backgrounds and highlighted the universality and specificity of
      youth suicide in Hong Kong.

PMID- 7624805
TI  - Perceived social support: psychometric properties of the MSPSS in normal and
      pathological groups in a developing country.
AB  - The factorial structure, reliability and construct validity of the
      Multidimensional Scale of Perceived Social Support (MSPSS) were investigated in
      Turkey to check the generality of some of the previous findings from Western
      samples. Using samples consisting of normals and subjects with medical or mental
      health problems, the original three factors (subscales) were obtained. The
      internal consistencies of the MSPSS and its subscales were high. In general, the
      scales correlated significantly in the expected direction with measures of
      depression and anxiety, thus supporting the construct validity of the MSPSS.
      Among the samples, subjects with psychiatric/psychological problems perceived, in
      general, the least social support. This result further contributed to the
      construct validity of the scale.

PMID- 7624806
TI  - Psychiatric morbidity among medical in-patients: a standardized assessment (GHQ
      12 and CIS-R) using 'lay' interviewers in a Brazilian hospital.
AB  - The 12-item General Health Questionnaire (GHQ-12) and the revised Clinical
      Interview Schedule (CIS-R) were used to estimate the prevalence of psychiatric
      morbidity among 78 consecutive admissions to a general medical ward in a
      Brazilian university hospital (43 males and 35 females; mean age = 43.2 years).
      The CIS-R was administered by three 5th-year medical students after a brief
      training. A prevalence rate of 36% was found for psychiatric disorders. The most
      frequent symptoms were sleep disorders (48.7%), worry (35.9%), depression (28.2%)
      and anxiety (26.9%). The sensitivity and specificity of the GHQ-12 were 71% and
      76%, respectively. The CIS-R was simple to administer and acceptable both to
      patients and interviewers. Misunderstanding was most likely to occur with the
      poorly educated (20% were illiterate) in questions involving time calculation.
      Alternative options might be used to specify the length of time in future
      studies. The findings support the feasibility of the CIS-R and the use of 'lay'
      interviewers to produce epidemiological information on psychiatric disorders in
      developing countries at lower costs.

PMID- 7624807
TI  - Has the sectorization of psychiatric services in France really been effective?
AB  - This paper describes the implementation of the French sectorization policy during
      the last 20 years, and how effectively it has delivered care to patients
      suffering from severe mental health disorders. This change in policy has resulted
      in a dramatic and progressive decline in full-time hospitalization and an
      increase in outpatient care, without, however, any marked increase in the
      readmissions rate. The resources and services provided by a representative
      section are described, followed by an account of a plan for closing psychiatric
      beds in a specific area of the centre of France. The full implementation of the
      policy has some distance to go, but the graded way in which it was carried out
      seems generally to have protected patients from adverse consequences. However,
      there has been little formal evaluation, and more is required before the policy
      can be deemed to have been successful.

PMID- 7624808
TI  - Drinking patterns of black and white men in the west Midlands.
AB  - The limited amount of evidence available from mortality statistics, mental
      hospital in-patient admission rates and community surveys appears to indicate
      that people of African-Caribbean origin resident in Britain have fewer alcohol
      related problems than the white population. However, there are no systematic data
      on the normal drinking habits of random and representative samples of the black
      population of Britain, or the true extent of alcohol-related problems in the
      whole population. A survey of the drinking habits and alcohol-related problems of
      random samples of 200 black men and 170 white men from the Birmingham and
      Wolverhampton areas is reported. Black men were much less likely to report
      regular drinking and to report drinking large amounts of alcohol. They were far
      less likely to have got drunk in the past year, and scored lower on most items of
      an Alcohol Problems Scale. Age was the only demographic variable associated with
      drinking levels in both groups, and the link was more tenuous in the black than
      the white group. There were no generational differences found. Religious
      observance and belonging to a Pentecostal Church were found to be major
      differences between the black and white groups, and strongly associated with
      moderation in relation to alcohol.

PMID- 7624810
TI  - Behavioral risk of human immunodeficiency virus/acquired immunodeficiency
      syndrome in the university student community.
AB  - BACKGROUND AND OBJECTIVES: Theoretically, university students could be at
      especially high risk in a human immunodeficiency virus-type epidemic. Peak
      incidence of human immunodeficiency virus infection occurs in this age group.
      GOALS OF THIS STUDY: The purpose of this study was to examine and characterize
      the behavior, attitudes, experiences, and knowledge of university students
      regarding human immunodeficiency virus/acquired immunodeficiency syndrome. STUDY
      DESIGN: A written survey was distributed to 405 students at a small, academically
      select university. Data were analyzed by the "Statistics With Finesse" program on
      a microcomputer. RESULTS: About 55% of the students considered themselves
      "sexually active," with 8.1% of these having had a sexually transmitted disease.
      Notwithstanding their concern and knowledge about human immunodeficiency
      virus/acquired immunodeficiency syndrome, a significant percentage reported
      participating in highly risky behavior. Therefore, they were at a behavioral risk
      of acquiring a human immunodeficiency virus infection and acquired
      immunodeficiency syndrome. CONCLUSIONS: All that is needed for the epidemic to
      rapidly spread into the tertiary-education student community is an increase in
      the exposure of that community to human immunodeficiency virus. Knowledge and
      concern about human immunodeficiency virus/acquired immunodeficiency syndrome did
      not appear to be sufficient to prevent risky behavior in this population. The
      results indicate a need to reconsider some of our human immunodeficiency
      virus/acquired immunodeficiency syndrome education and prevention efforts.

PMID- 7624809
TI  - Prevalence of depression in an aged population in Finland.
AB  - The prevalence of depression by sex, age and certain sociodemographic variables
      was investigated among elderly Finns (65 years or over) living in the semi
      industrialized town of Ahtari (n = 1225). The prevalence of depression,
      determined using the DSM-III criteria, was 16.5% for the total population, 14.4%
      for the men and 17.9% for the women. Dysthymic disorder was the commonest
      category of depression in both sexes, with atypical depression the second most
      common category among the men and major depression among the women. A few cases
      of cyclothymic disorder were diagnosed in each sex, but no cases of bipolar
      depression. The occurrence of depression was not associated with sex, but it was
      related to older age, widowhood and lower educational level in the men, although
      not in the women. In both sexes, a high risk of depression was associated with
      being in long-term institutional care and receiving home nursing and/or a home
      help. The occurrence of depression was not related to earlier occupation.

PMID- 7624811
TI  - Susceptibility of isolates of Neisseria gonorrhoeae to penicillin and
      tetracycline in Brooklyn, 1988-1992.
AB  - BACKGROUND AND OBJECTIVES: The aim of this analysis was to determine the rate of
      resistance of Neisseria gonorrhoeae to penicillin and tetracycline over 5 years.
      STUDY DESIGN: The authors studied 500 isolates of N. gonorrhoeae. Minimum
      inhibitory concentrations of various antimicrobial agents, including penicillins,
      tetracyclines, quinolones, cephalosporins, spectinomycin, and trospectomycin,
      were determined using agar dilution. Organisms that produced beta-lactamase were
      classified as penicillinase-producing N. gonorrhoeae, and those with tetracycline
      minimum inhibitory concentrations > 16 micrograms/ml were considered presumptive
      high-level tetracycline resistant. Organisms with Minimum inhibitory
      concentrations > 2.0 micrograms/ml were presumptively considered to have
      chromosomally mediated resistance to penicillin or tetracycline. Isolates with
      none of these forms of resistance were considered susceptible to penicillin and
      tetracycline. RESULTS: Penicillinase-producing N. gonorrhoeae represented 34.7%,
      40.7%, and 44.9% of gonococcal isolates in 1988, 1989, and 1990, respectively.
      Only 14.3% and 15.0% of the isolates in 1991 and 1992 were penicillinase
      producing N. gonorrhoeae. In 1988, 1.0% of isolates were chromosomally mediated
      penicillin resistant. In contrast, chromosomally mediated penicillin resistant
      gonococci represented 7.5% to 22.4% of isolates from 1989 to 1992. In 1988, 26.0%
      of isolates were high-level tetracycline resistant. The prevalence of presumptive
      high-level tetracycline resistant organisms decreased after 1988. From 1989 to
      1992, only 8.2% to 14.8% of gonococcal isolates were presumptive high-level
      tetracycline resistant. No chromosomally mediated tetracycline resistant isolates
      were identified in 1988. In 1989 and 1990, 11.6% and 10.2%, respectively, of
      isolates were chromosomally mediated tetracycline resistant. Chromosomally
      mediated tetracycline resistant N. gonorrhoeae represented 2.0% of isolates in
      1991 and 25.0% of isolates in 1992. All isolates tested were susceptible to the
      other antibiotics. CONCLUSION: Continued surveillance of sensitivity of
      contemporary gonococci to antimicrobial agents is important.

PMID- 7624813
TI  - Lifetime number of partners as the only independent risk factor for human
      papillomavirus infection: a population-based study.
AB  - BACKGROUND AND OBJECTIVES: Previous studies of relationships between genital
      human papillomavirus infection and tentative risk factors have yielded
      conflicting results, possibly because of inaccuracy of the viral detection
      methods used and differences in selection criteria. GOAL OF THIS STUDY: To
      determine human papillomavirus prevalence and identify risk factors in a group of
      young Swedish women. STUDY DESIGN: This was a population-based study involving
      completion of a structured questionnaire, analysis of cervical scrapings for
      human papillomavirus and Chlamydia trachomatis, and serologic tests for C.
      trachomatis and herpes simplex virus antibodies. RESULTS: The prevalence of human
      papillomavirus infection was 22% among the sexually active women and 4% among the
      virgins. A number of factors were associated with human papillomavirus prevalence
      in univariate analysis, but logistic regression analysis showed that lifetime
      number of male sexual partners was the only independent risk factor for human
      papillomavirus infection (adjusted odds ratio, 7.45; 95% CI, 2.79-19.92 for six
      or more partners vs. one partner). CONCLUSION: Human papillomavirus infection is
      a prevalent sexually transmitted disease among young Swedish women, and the
      lifetime number of male sexual partners is a major risk factor.

PMID- 7624812
TI  - Prevalence of human papillomavirus among STD clinic attenders in Jamaica:
      association of younger age and increased sexual activity.
AB  - BACKGROUND AND OBJECTIVES: Human papillomavirus is the major etiologic agent of
      cervical cancer. Although the incidence of cancer of the cervix is high in
      Jamaica, the prevalence of human papillomavirus among Jamaican women has not been
      defined. GOAL OF THE STUDY: To estimate the prevalence of human papillomavirus
      infection and associated risk factors in women attending an STD clinic in
      Kingston, Jamaica. STUDY DESIGN: A cross-sectional survey was done of 202 women
      attending an STD clinic in Kingston in 1990. Cervical and vaginal cells were
      collected by lavage, and human papillomavirus genomes were detected in extracted
      DNA using low-stringency Southern blot hybridization. RESULTS: Fifty-eight
      (28.7%) women were identified as HPV positive. Prevalence of HPV by age group was
      39% in women 15-19 years old, 33% of women 20-24 years old, 31% in women 25-29
      years old, and 17% in those 30 years or older. Increasing age was significantly
      associated with a lower prevalence of human papillomavirus infection (test for
      trend, P = 0.025). The effect of age was independent of years of sexual activity.
      Women reporting more than one sexual partner per month on average were found to
      have a significantly higher HPV prevalence (odds ratio 2.87, 95% confidence
      Interval 1.29-6.38), as were women who reported more frequent sex (test for
      trend, P = 0.006). CONCLUSIONS: Sexual behavior is associated with risk of human
      papillomavirus infection. The decrease of human papillomavirus prevalence in
      older women agrees with other studies that argue in favor of a biological effect,
      such as increased immunity to human papillomavirus with age. A better
      understanding of why immunity to human papillomavirus may develop in older women
      may provide the basis for developing an effective vaccine to prevent cancer of
      the cervix.

PMID- 7624814
TI  - DNA amplification fingerprinting for subtyping Neisseria gonorrhoeae strains.
AB  - BACKGROUND AND OBJECTIVES: DNA amplification fingerprinting is used in most
      epidemiologic studies as a substitute for conventional typing methods. DNA
      amplification fingerprinting and conventional typing methods were compared in
      this epidemiologic study of Neisseria gonorrhoeae. GOAL OF THIS STUDY: To
      differentiate 70 Neisseria gonorrhoeae isolates from untreated patients with
      urogenital gonococcal infection. STUDY DESIGN: Gonococcal strains were
      characterized by auxotyping, serotyping, plasmid profile, antibiotic sensitivity,
      and DNA amplification fingerprinting. The method of unweighted pair-group average
      linkage was used for cluster analysis. Discriminatory power was calculated
      applying Simpson's index. RESULTS: Amplification of Neisseria gonorrhoeae DNA
      with primers OPA-03 and OPA-13 produced well-resolved patterns of 15 and 22 DNA
      fragments, respectively, with a discriminatory power (0.978 with OPA-13 and 0.967
      with OPA-03) comparable to that obtained with auxotyping/serotyping combination
      (D:0.968) or with auxotype/serotype/plasmid profile combination (D:0.983).
      Correlation between DNA amplification fingerprinting pattern and
      auxotype/serotype class was not always uniform. Some strains with the same
      auxotype/serotype/plasmid profile were subdivided by DNA amplification
      fingerprinting, and vice versa. CONCLUSION: Although auxotype/serotype class and
      DNA amplification fingerprinting can be used in the epidemiologic
      characterization of strains, DNA amplification fingerprinting offers a better
      discriminatory index than the separate serotyping. It is especially useful for
      differentiating serologically identical strains and nontypable strains. A
      combination of serotyping and DNA amplification fingerprinting seems to be the
      best way to differentiate Neisseria gonorrhoeae strains in epidemiologic studies,
      bringing together the most simple techniques and the best discriminatory power
      among isolates.

PMID- 7624815
TI  - Tubal infertility: serologic relationship to past chlamydial and gonococcal
      infection. World Health Organization Task Force on the Prevention and Management
      of Infertility.
AB  - BACKGROUND AND OBJECTIVES: Sparse data exist for quantifying the association
      between Chlamydia trachomatis infection, salpingitis, and tubal infertility. GOAL
      OF THIS STUDY: To investigate the impact of Neisseria gonorrhoeae and C.
      trachomatis in tubal infertility. STUDY DESIGN: This was a multicenter case
      control study that compared women who have bilateral tubal occlusion with other
      infertile women and age-matched pregnant control subjects. Reproductive and
      sexual history were recorded, and immunoglobulin G antibodies to C. trachomatis
      and N. gonorrhoeae were measured. RESULTS: Women with past chlamydial or
      gonococcal infections or both were significantly more likely to have bilateral
      tubal occlusion. The majority of women with bilateral tubal occlusion reported no
      history of pelvic inflammatory disease symptoms. Other infertile women had a
      prevalence of C. trachomatis antibodies (60%), which was similar to that of
      patients with bilateral tubal occlusion (71%). CONCLUSION: Sexually transmitted
      infections, especially C. trachomatis, are associated with tubal infertility.
      Because they usually cause no symptoms, public health efforts to prevent tubal
      infertility should focus on identifying infections in the lower genital tract
      before they ascend.

PMID- 7624816
TI  - Prevalence of sexually transmitted diseases in Mexican-American pregnant women by
      country of birth and length of time in the United States.
AB  - BACKGROUND AND OBJECTIVES: The prevalence of sexually transmitted diseases in
      Hispanic prenatal patients has not been well documented. Studies of disease
      prevalence in Hispanic patients often are complicated by multiple countries of
      origin and the combining of foreign-born and U.S.-born Hispanics into a single
      category. GOAL OF THE STUDY: The purpose of this study was to document the
      prevalences of sexually transmitted diseases in low-income, pregnant Mexican
      American women and to compare the prevalences of those born in the United States
      with those born in Mexico. We also compared the prevalence of those who recently
      arrived from Mexico with those who had been in the United States a longer time.
      STUDY DESIGN: Three-hundred-forty-seven pregnant women attending a clinic for low
      income populations were screened for syphilis, gonorrhea, chlamydia, and
      hepatitis B virus on their first perinatal visit. RESULTS: Thirty-five women
      (10.1%) were positive for chlamydia, four (1.2%) for gonorrhea, one (0.3%) for
      syphilis, and none for hepatitis B virus. Women born in Mexico reported fewer
      past chlamydia and total sexually transmitted disease infections than Mexican
      Americans and non-Hispanic whites born in the United States However, the
      prevalence of chlamydia and total sexually transmitted diseases did not differ by
      ethnicity, country of birth, or length of time in the United States The only
      variable correlated with chlamydia infection was the presence of vaginal
      discharge, but the sensitivity of this symptom was too low to be clinically
      useful as a means of selective screening. CONCLUSION: Low-income women of Mexican
      ancestry should be routinely screened for syphilis, gonorrhea, and chlamydia as
      part of their prenatal care in the United States. The value of hepatitis B virus
      screening in this population was neither supported nor refuted by this study.

PMID- 7624817
TI  - Trichomoniasis in men: old issues and new data.
AB  - BACKGROUND AND OBJECTIVES: Trichomoniasis is common among sexually active women,
      but its importance as a cause of morbidity among sexually active men remains
      uncertain. STUDY DESIGN: The article outlines areas of controversy and presents
      pertinent new data from case-control and natural history studies. RESULTS:
      Trichomonas vaginalis was documented in 11% of 447 men at risk for a sexually
      transmitted disease. Although 54% of infected men complained of urethral
      discharge, the discharge was only mild or moderately severe. Elimination of
      Trichomonas vaginalis was associated with resolution of urethritis. CONCLUSIONS:
      Trichomonas vaginalis is an important consideration in sexually active men with
      urethral symptoms or inflammation but with little or no evidence of discharge on
      physical examination.

PMID- 7624819
TI  - Average hospital charges for percutaneous transluminal coronary angioplasty,
      1993: geographic variations.
AB  - Claims to Metropolitan Life Insurance Company by group health insured and their
      dependents for a percutaneous transluminal coronary angioplasty (PTCA) averaged
      $21,760 in 1993. The charges varied by as much as 68 percent among the 22 states
      in which at least 50 PTCAs were performed. The highest average total charges were
      reported in Colorado and California, where they were 29 and 26 percent,
      respectively, above the average for the United States as a whole. The lowest
      average total charge was reported in Ohio, where the PTCA cost $16,770-23 percent
      lower than the national average. An average of 4.3 days of hospitalization was
      required for a PTCA. Hospital charges (room and board and ancillary fees)
      accounted for 78 percent of the total PTCA charges to insurance. The charges for
      the operating room, laboratory, blood bank, respiratory therapy and other
      ancillary fees together accounted for 80 percent of the total hospital bill and
      averaged $13,550 for the country as a whole. Physicians' fees averaged $4,740
      across the United States and ranged from a high of $5,930 in Connecticut to a low
      of $3,730 in Michigan. These PTCA total charges were close to half the charge
      reported for a coronary artery bypass graft (CABG) in 1992 and the length of stay
      was also about half that for a CABG.

PMID- 7624818
TI  - The effectiveness of video-based interventions in promoting condom acquisition
      among STD clinic patients.
AB  - GOAL OF THIS STUDY: This study examined the effectiveness of video-based patient
      education interventions on promoting condom use among men and women seeking
      services at a large public STD clinic in New York City. METHODS: Culturally
      sensitive video-based interventions designed to promote safer sex behaviors were
      evaluated in a randomized study of black and Hispanic male and female STD clinic
      patients. Subjects (n = 1,653) were randomly assigned to one of three groups: 1)
      control, 2) video viewing, and 3) video viewing followed by participation in an
      interactive group session led by a trained facilitator. The authors examined 1)
      the effectiveness of interventions in increasing STD and condom-related
      knowledge, positive attitudes about condoms, human immunodeficiency virus/STD
      risk perceptions, and self-efficacy and 2) the relationships among these
      variables, level of intervention, and condom acquisition, a behavioral measure of
      condom use. RESULTS: Compared with a control group, subjects assigned to video
      viewing demonstrated greater knowledge about condoms and STDs, more positive
      attitudes about condom use, increased human immunodeficiency virus/STD risk
      perceptions, greater self-efficacy, and higher rates of condom acquisition.
      Subjects assigned to video viewing followed by interactive sessions demonstrated
      still further increases in risk perceptions, self-efficacy, and condom
      acquisition, but not in knowledge or condom attitudes. A significant proportion
      of the association between the behavioral outcome of condom acquisition and level
      of intervention is attributable to the impact of interventions on risk perception
      and self-efficacy. CONCLUSIONS: Based on extensive formative research that
      identified barriers to safer sex behaviors, video-based interventions were
      developed to promote condom use among black and Hispanic men and women attending
      STD clinics. Designed to be integrated into clinic services, these interventions
      help improve knowledge, promote positive attitudes about condoms, and increase
      condom acquisition among individuals at high risk of acquiring and transmitting
      human immunodeficiency virus infection and other STDs.

PMID- 7624820
TI  - Trend in mortality from violent deaths: unintentional injuries, United States,
      1960-1991.
AB  - Deaths from unintentional injuries were the fifth leading cause of death in 1991
      after ranking fourth for more than a decade. In 1991 these deaths totaled 89,347
      for a rate of 35.4 per 100,000. Mortality rates among men aged 15 and over
      increased 1.7 percent per year between 1960 and 1967, declined 2.2 percent
      annually between 1968 and 1978 and by 2.9 percent each year from 1979 to 1991.
      Similar rate changes were evident among women. Deaths from motor-vehicle
      accidents account for almost half of all deaths from unintentional injuries; the
      1991 mortality rate was 17.3 per 100,000 population. Age-adjusted motor vehicle
      death rates continue to be much higher among men than women but the gap is
      decreasing. The male to female ratio was 3.3:1 in 1960 but dropped to 2.5:1 in
      1991. Mortality from motor-vehicle accidents peaked for men aged 15 and over at
      53.1 per 100,000 in 1968 after rising from 42.4 in 1960. The rate declined
      irregularly to 29.9 in 1991. Among same-aged women, motor-vehicle mortality rates
      peaked in 1969 at 17.1 per 100,000 population, up from 12.7 in 1960. After
      reaching a low of 12.1 per 100,000 in 1975, the rates have tended to increase but
      dropped to 11.9 in 1991. Unintentional-injury mortality continues to claim large
      numbers of young lives. These deaths were the leading cause of death at ages 15
      44 for all races and sexes combined in 1991 and motor-vehicle deaths, alone, were
      the leading cause of death at ages 15 to 24. All other unintentional-injury
      deaths ranked fourth in this age group.

PMID- 7624821
TI  - The registered nurse workforce: infrastructure for health care reform.
AB  - As of March 1992, 83 percent of America's more than 2.2 million licensed
      registered nurses (RNs) were actively employed in nursing. RNs are the largest
      group of U.S. health care professionals and constitute a major part of the
      infrastructure necessary to any health care reform agenda. Therefore, it is
      critical to assess the extent to which the current nurse workforce is adequately
      prepared for its future role in a reformed health care system. Two central trends
      in the composition of the nurse workforce are noteworthy. First, while the number
      of RNs is large and continues to grow, cyclical, demand-driven shortages have
      occurred nationally since World War II. Further, hospital cost containment
      strategies periodically depress nurses' relative wages, contributing to the
      substitution of RNs for other workers. Second, there is concern in nursing, as in
      medicine, that the RN workforce is not optimally trained to meet future needs.
      While two-year associate degree programs now produce a majority of nursing
      graduates, the greatest need is for advanced practice nurses. Demand for such
      nurses is high and is expected to increase as more of the population gains access
      to health care services. The incentives put forth in the health care reform
      debate--expanded health insurance coverage, integrated health care delivery
      systems, and cost-effective practice--create the potential for expanded roles and
      increased job opportunities for nurses. Realizing this potential will depend
      largely on the profession's responsiveness to the changes confronting it under
      health care reform.

PMID- 7624823
TI  - MK-801 disrupts the expression but not the development of bromocriptine
      sensitization: a state-dependency interpretation.
AB  - Repeated administration of the D2-type agonist bromocriptine (5.0 mg/kg, IP)
      caused progressive increases in the locomotor-stimulating effects of the drug in
      rats. Similar progressive increases in locomotor activity were observed in rats
      that received repeated coadministration of the NMDA receptor antagonist MK-801
      (0.25 mg/kg, IP) plus bromocriptine. However, when rats previously treated with
      the combination of drugs received either bromocriptine or MK-801 alone, their
      levels of activity were comparable to those of rats having no prior experience
      with either drug. A second group of rats was sensitized to the effects of
      bromocriptine alone; no evidence of bromocriptine sensitization was seen when MK
      801 was subsequently coadministered with bromocriptine. Thus, either the presence
      or the absence of MK-801 could--depending upon the conditions of previous drug
      treatment--block the expression of bromocriptine sensitization. When a third
      group of rats was sensitized to the combination of MK-801 plus bromocriptine and
      subsequently tested following 2 or 6 drug-free weeks, evidence of sensitized
      responses was still present. Thus, at the very least, blockade of NMDA receptors
      with MK-801 fails to compromise the cellular changes associated with
      sensitization to the repeated combination of MK-801 plus bromocriptine.
      Bromocriptine sensitization may prove to be unique in this regard, but the
      present findings suggest a control condition that should be carefully explored in
      studies of the effects of MK-801 on sensitization involving other stimulant
      drugs.

PMID- 7624822
TI  - Health care costs: market forces and reform.
AB  - The cost of health care remains an important issue for the U.S. economy. Health
      care expenditures in 1995 are projected to be over $1 trillion, with the annual
      growth rate expected to average 8 percent for the 1990-95 period. National health
      expenditures were equivalent to 13.9 percent of the Gross Domestic Product (GDP)
      in 1993; 1995 estimates place the ratio at 14.3 percent. The medical care
      Consumer Price Index for 1994 has shown the smallest increase since 1973 (4.8
      percent). This result followed a gain of 5.9 percent in 1993. Health care
      spending varies by region, with New England having the highest per capita
      spending and the Rocky Mountain states having the lowest. States with the highest
      proportions of the population over age 65 tend to be those with the highest
      health care costs, as well as growth rates, in the country.

PMID- 7624824
TI  - GABAergic projection from the ventral pallidum and globus pallidus to the
      subthalamic nucleus.
AB  - There exists a topographically organized projection from the globus pallidus and
      ventral pallidum to the subthalamic nucleus and adjacent lateral hypothalamus.
      The participation of GABA as a neurotransmitter in this projection was evaluated
      by retrograde labeling of cells in the pallidal area from an iontophoretic
      deposit of Fluor-Gold in the subthalamus combined with in situ hybridization for
      mRNA of the GABA synthetic enzyme, glutamate decarboxylase (GAD). A rostrocaudal
      gradient in the contribution of GABA to the projection was demonstrated with a
      relatively small percentage of retrogradely labeled cells in the rostral ventral
      pallidum containing GAD mRNA (7%) compared to the caudal globus pallidus which
      had over 70% of the Fluoro-Gold containing cells double-labeled for GAD mRNA.
      Overall the ventral pallidum contribution to the subthalamic nucleus was less
      GABAergic than the portion arising from the globus pallidus (35% vs. 61%,
      respectively).

PMID- 7624825
TI  - Developmental changes in long-term potentiation in CA1 of rat hippocampal slices.
AB  - Long-term potentiation (LTP) was examined in the CA1 region of rat hippocampal
      slices at postnatal day 9 (P9), P15, P30, P60, P90, P120, and P300. A single 100
      Hz x 1 sec tetanus failed to induce LTP in P9 slices, while similar degrees of
      LTP were observed at P15, P30, and P60. At P30, changes in population spike (PS)
      amplitudes were accurately predicted by changes in dendritic excitatory
      postsynaptic potentials (EPSPs). However, at P15, the predicted increase in PS
      calculated from corresponding changes in dendritic EPSPs was significantly less
      than the observed increase, suggesting that EPSP-PS dissociation (ES
      dissociation) plays a substantial role in LTP at P15. Additionally, the
      corresponding changes in somatic EPSP height measured in the CA1 cell layer did
      not predict the E-S dissociation at P15, suggesting that the E-S dissociation
      arises largely from changes in the excitability of the soma. Using a single 100
      Hz x 1 sec tetanus, LTP proved difficult to induce in slices from rats > or =
      P90, with slices showing initial enhancement that faded over 60 min of
      monitoring.

PMID- 7624826
TI  - Synaptic transmission blockade increases plasminogen activator activity in mouse
      skeletal muscle poisoned with botulinum toxin type A.
AB  - Experimental denervation, either by nerve crush or axotomy, leads to a dramatic
      increase in muscle plasminogen activator (PA) activity, suggesting a regulation
      of muscle PA levels by some neural influence (Festoff et al., 1986, J. Cell
      Biol., 103:1415-1421; Hantai et al., 1990, Proc. Natl. Acad. Sci. U.S.A., 87:2926
      2930). The Botulinum toxin (BoTx) type A is known to selectively interrupt the
      release of acetylcholine without structurally altering synaptic morphology. In
      the present study we have used acute BoTx poisoning of hind limb muscles to
      further explore the neural regulation of muscle PA activities directly after
      poisoning and during the process of collateral reinnervation. Electromyographic
      recording and study of ultraterminal sprouting after zinc iodideosmium and silver
      cholinesterase staining were used to monitor "denervation" and reinnervation.
      Muscle choline acetyltransferase activity did not decrease, as is observed after
      experimental denervation, but in contrast increased and, therefore, reflected the
      functional integrity of intramuscular nerve endings. Within 2 days of BoTx
      poisoning, muscle urokinase-PA, and to a lesser extent, tissue-PA activities,
      rose in muscle extracts as shown by an amidolytic assay and fibrin zymography.
      When reinnervation occurred, muscle urokinase-PA activity decreased but did not
      return to baseline levels within the 80 days of our study. These results suggest
      that cholinergic transmission-regulated events determine activity of muscle PAs
      and that PAs likely have a role in neuromuscular formation and plasticity.

PMID- 7624827
TI  - Sensitization to cocaine and dopamine autoreceptor subsensitivity in the nucleus
      accumbens.
AB  - It has been suggested that dopamine autoreceptor subsensitivity may play a role
      in cocaine-induced behavioral sensitization. In order to evaluate this
      hypothesis, we administered cocaine to rats daily (15 mg/kg ip x 2 days, 30 mg/kg
      ip x 5 days) and then monitored nucleus accumbens dopamine during the local
      administration (through the dialysis probe) of the D2/D3 agonist, quinpirole (0,
      0.1, 1, and 10 microM). Our results indicate that, relative to saline-pretreated
      control animals, repeated cocaine administration impaired the ability of
      quinpirole to decrease extracellular dopamine 1-2 days after the last drug
      injection. However, quinpirole was equipotent at reducing accumbal dopamine in
      cocaine- and saline-treated animals following a 21-22 day withdrawal period.
      These results demonstrate that repeated cocaine produces a short duration
      functional tolerance in the capacity of autoreceptor stimulation to inhibit
      accumbal dopamine release.

PMID- 7624829
TI  - Increase in synaptic vesicle proteins in synapsin-transfected NG108-15 cells: a
      subcellular fractionation study.
AB  - We have examined the subcellular distribution of synapsins and synaptophysin in
      density gradients from synapsin- and vector-transfected NG108-15 cells, since we
      recently found that transfection of synapsin IIb cDNA into neuroblastoma x glioma
      hybrid cells (NG108-15) resulted in cell lines that had a more neuronal phenotype
      than controls. The increase in synapsins and synaptophysin in the transfected
      cells was maximal in the region of the gradient containing small synaptic
      vesicles. The transferrin receptor, a marker for early endosomes, did not
      increase in the synapsin-containing fractions in the transfected cells.
      Secretogranin I, a soluble protein stored in and secreted from large dense cored
      vesicles, showed a very pronounced increase in the dense regions of gradients
      from transfected cells. These subcellular fractionation data suggest a possible
      role for the synapsins in the regulation of synaptic vesicle function.

PMID- 7624828
TI  - Positron emission tomography imaging of serotonin transporters in the human brain
      using [11C](+)McN5652.
AB  - This paper presents the first Positron Emission Tomography (PET) images of the
      serotonin (5-hydroxytryptamine, 5-HT) transporter in the living human brain. PET
      imaging was performed in three healthy subjects after administration of
      [11C](+)McN5652 (the (+) enantiomer of trans-1,2,3,5,6,10 beta-hexahydro- 6-[4
      (methylthio) phenyl]pyrrolo-[2,1-a] -isoquinolone), a radioligand previously
      shown to selectively label the 5-HT transporter in vivo in the mammalian (mouse
      and baboon) brain. To demonstrate the specificity of [11C](+)McN5652 binding,
      additional images were obtained in the same subjects after injection of [11C](
      )McN5652, the pharmacologically inactive enantiomer, and, in two of the subjects,
      with [11C](+)McN5652 after pretreatment with the 5-HT uptake site blocker
      fluoxetine. Highest accumulation of [11C](+)McN5652 was observed in the midbrain,
      putamen, caudate nucleus, hypothalamus, and thalamus, regions known to contain
      high densities of 5-HT transporters. In these areas [11C](+)McN5652
      concentrations rose steadily over 120 min. In contrast, with [11C](-)McN5652 and
      when the [11C](+)McN5652 binding was inhibited with fluoxetine, radioactivity
      concentrations declined after reaching a maximum (at 20 to 30 min). Inhibition
      studies with fluoxetine suggest that only with [11C](+)McN5652, there is specific
      binding. In the cerebellum, a region relatively void of 5-HT transporters, both
      [11C](+)McN5652 with and without fluoxetine block and [11C](-)McN5652 were
      released at approximately the same rate. The results of the studies indicate that
      [11C](+)McN5652 labels 5-HT transporter sites in the human brain. Quantitative
      PET imaging studies with this new tracer should provide valuable information on
      the status of these sites in health and disease.

PMID- 7624830
TI  - Pre- and post-synaptic effects of the 5-HT3 agonist 2-methyl-5-HT on the 5-HT
      system in the rat brain.
AB  - Microiontophoretic applications of 5-HT and of the 5-HT3 agonist 2-methyl-5-HT
      produced a current-dependent suppression of firing activity of both hippocampal
      (CA1 and CA3) and cortical neurons in anesthetized rats. Concomitant
      microiontophoretic applications of the 5-HT3 antagonists BRL 46470A and S
      zacopride, as well as their intravenous injection, did not antagonize the
      inhibitory effect of 5-HT and 2-methyl-5-HT. In contrast, the 5-HT1A antagonist
      BMY 7378, applied by microiontophoresis or administered intravenously,
      significantly reduced the inhibitory action of 5-HT and 2-methyl-5-HT. The firing
      activity of dorsal raphe 5-HT neurons was also reduced by 5-HT, 2-methyl-5-HT and
      the 5-HT1A agonist 8-OH-DPAT applied by microiontophoresis. While BRL 46470A (0.1
      and 1 mg/kg, i.v.) did not antagonize the inhibitory effect of the three 5-HT
      agonists on 5-HT neuronal firing activity, only that of 8-OH-DPAT was attenuated
      by the 5-HT1A antagonist (+) WAY 100135. R-zacopride significantly reduced the
      duration of suppression of firing activity of CA3 pyramidal neurons induced by
      the electrical stimulation of the ascending 5-HT pathway, and this reducing
      effect was prevented by the three 5-HT3/5-HT4 antagonists renzapride, S-zacopride
      and tropisetron, but not by BRL 46470A. Finally, in in vitro superfusion
      experiments, both BRL 46470A and S-zacopride antagonized the enhancing action of
      2-methyl-5-HT on the electrically-evoked release of [3H]-5-HT in both rat frontal
      cortex and hippocampus slices. These findings suggest that, in vivo, the
      suppressant effect of 2-methyl-5-HT on the firing activity of dorsal hippocampus
      pyramidal, somatosensory cortical, and dorsal raphe 5-HT neurons is not mediated
      by 5-HT3 receptors, but rather by 5-HT1A receptors. The attenuating effect of R
      zacopride on the effectiveness of the stimulation of the ascending 5-HT pathway
      is not mediated by 5-HT3 receptors. In contrast, in vitro, the enhancing action
      of 2-methyl-5-HT on the electrically-evoked release of [3H]5-HT in both frontal
      cortex and hippocampus slices is mediated by 5-HT3 receptors.

PMID- 7624831
TI  - NMDA antagonists and clonidine block c-fos expression during morphine withdrawal.
AB  - The c-fos gene is expressed in the central nervous system (CNS) in response to
      neuronal stimuli. Induction of c-fos in certain CNS regions occurs following
      naltrexone precipitated withdrawal in morphine dependent rats. Non-competitive
      (MK801) and competitive (LY274614) NMDA receptor antagonists and clonidine, an
      alpha2 partial agonist, attenuate the intensity of naltrexone precipitated
      withdrawal. We determined the levels of c-fos mRNA by solution hybridization in
      several brain regions in control and morphine dependent rats following
      pretreatment with saline, MK801 (1 mg/kg, s.c.), LY274614 (100 mg/kg, i.p.), or
      clonidine (1.5 mg/kg, i.p.). Morphine treatment increased c-fos mRNA levels in
      striatum (STR) and amygdala (AMY). Naltrexone did not alter c-fos mRNA levels in
      placebo-treated rats. However, naltrexone increased c-fos mRNA levels in morphine
      dependent rats in the nucleus accumbens (NA), frontal cortex (FC), AMY, and
      hippocampus (HIP) but not in STR or spinal cord. Pretreatment with MK801 blocked
      this effect of naltrexone in AMY but not in NA, FC, or HIP, while pretreatment
      with LY274614 or clonidine blocked this effect of naltrexone in AMY and NA but
      not in FC or HIP. These results further delineate both the neuroanatomical
      pathways involved in morphine withdrawal and the locus of action of compounds
      that reduce morphine-withdrawal symptoms.

PMID- 7624832
TI  - Immunochemical localization of calcium/calmodulin-dependent protein kinase I.
AB  - Ca2+/calmodulin-dependent protein kinase I (CaM kinase I) was originally
      identified in rat brain based on its ability to phosphorylate site 1 of synapsin
      I. Recently a cDNA for the rat brain enzyme has been cloned and the primary
      structure elucidated [Picciotto et al. (1993), J. Biol. Chem., 268:26512-26521].
      The rat cDNA encoded a protein of 374 amino acids with a calculated M(r) of
      41,636. Antibodies have now been raised against the recombinant kinase expressed
      in E. coli as a glutathione-S-transferase fusion protein. Immunoblot analysis of
      rat cortex lysates revealed two major immunoreactive bands of approximately M(r)
      38,000 and 42,000. Minor immunoreactive species of slightly lower M(r) were also
      detected. Two distinct CaM kinase I activities were partially purified from rat
      brain and shown to correspond to the two major immunoreactive species. A variety
      of immunoreactive species of M(r) 35-43,000 were detected in "brain" tissue from
      cow, zebra finch, goldfish, Xenopus, lamprey, and Drosophila. In rat brain,
      immunocytochemistry revealed strong staining in cortex, hippocampus, amygdala,
      hypothalamus, brain stem, and choroid plexus. The labelling was mainly observed
      in neuropil but clusters of intensely labelled neuronal cell bodies were also
      detected all along the neuraxis. Neuronal nuclei and glial cells did not appear
      to be stained. Subcellular fractionation studies confirmed the cytosolic
      localization of the kinase in the brain. In various rat non-neuronal tissues and
      in a number of cell lines, immunoreactive species of approximately M(r) 38,000
      and approximately 42,000 were detected at lower levels than that detected in
      brain. The M(r) 38,000 and 42,000 species were also found in different ratios and
      at different levels in the non-neuronal tissues. These results support a role for
      CaM kinase I in the regulation of multiple neuronal processes. Furthermore, the
      widespread cell and tissue distribution suggests that CaM kinase I may function
      as a ubiquitous multi-functional protein kinase. Finally, the multiple
      immunoreactive species may represent isoforms of CaM kinase I.

PMID- 7624833
TI  - In vivo labeling of sigma receptors in mouse brain with [3H]4-phenyl-1-(4
      phenylbutyl)piperidine.
AB  - 4-Phenyl-1-(4-phenylbutyl)piperidine (4-PPBP) is a very potent ligand for sigma
      (Sigma) receptors. The present study was undertaken to evaluate [3H]4-PPBP as a
      radioligand for in vivo labeling of cerebral sigma receptors. After intravenous
      administration of [3H]4-PPBP to mice, there is high uptake of radioactivity in
      the brain. The regional distribution of radioactivity in the brain 2 h after
      intravenous injection of [3H]4-PPBP parallels the in vitro binding of the
      radioligand in rat brain (pons/medulla > cerebellum > or = prefrontal cortex > or
      = parietal cortex > hypothalamus > olfactory tubercle > or = thalamus >
      hippocampus > striatum). Pretreatment with haloperidol (2 mg/kg) significantly
      decreases the radioactivity measured in the brain 30-120 min after injection of
      [3H]4-PPBP. Pretreatment with unlabeled 4-PPBP or ifenprodil also significantly
      decreases radioactivity in the brain 2 h after injection of [3H]4-PPBP, in a dose
      dependent manner. The in vivo binding of [3H]4-PPBP in the brain also is
      significantly inhibited by SL 82.0715, BMY 14802, 1,3-di-o-tolylguanidine (DTG),
      and (+)-enantiomers of pentazocine, SKF 10,047, and 3-PPP, but not by the
      corresponding (-)-enantiomers, consistent with stereoselectivity of inhibition
      obtained in in vitro binding studies. In contrast, pretreatment with dizocilpine
      and spiperone does not inhibit in vivo binding of [3H]4-PPBP. The results
      indicate that [3H]4-PPBP would be a suitable radioligand for in vivo labeling of
      sigma receptors in brain.

PMID- 7624835
TI  - The Teratology Society 35th annual meeting. Newport Beach, California, June 24
      29, 1995. Abstracts.

PMID- 7624834
TI  - Effect of calpain on the composition and structure of postsynaptic densities.
AB  - Endogenous calcium-activated proteases, the calpains, are thought to play a role
      in the regulation of postsynaptic function. Here we characterize some biochemical
      and morphological effects of calpain on isolated postsynaptic densities (PSDs).
      When a PSD preparation from rat forebrain was treated with exogenous calpain,
      many proteins, including spectrin, tubulin and the alpha-subunit of calcium
      calmodulin-dependent protein kinase (alpha-CaM kinase), were proteolyzed at
      varying rates, while another major protein, actin, remained intact. The
      selectivity of calpain action became more apparent in experiments designed to
      achieve limited proteolysis by using a lower calpain-to-protein ratio; it was
      possible to obtain extensive breakdown of spectrin with no decrease in the levels
      of either tubulin, alpha-CaM kinase, or actin. Electron microscopy of freeze
      substituted preparations showed that limited calpain action caused a partial
      unraveling of the PSD, in which the characteristic central dense lamina became
      wider and less dense. We interpret these changes as due to calpain-mediated
      breakdown of cross-bridging elements, leading to a partial unraveling of the
      central PSD lamina. Opening up of the PSD structure following limited calpain
      action could facilitate exposure of previously occluded functional sites within
      the PSD and contribute to the modification of the synaptic function.

PMID- 7624837
TI  - Increased procoagulant and antifibrinolytic activities in the lungs with
      idiopathic pulmonary fibrosis.
AB  - To elucidate the pathophysiology of idiopathic pulmonary fibrosis (IPF), we
      examined procoagulant (tissue factor:TF), fibrinolytic (tissue type plasminogen
      activator:t-PA and urokinase type plasminogen activator:u-PA) and
      antifibrinolytic (plasminogen activator inhibitor-1:PAI-1 and PAI-2) activities
      in bronchoalveolar lavage (BAL) supernatant fluids and BAL cell lysates obtained
      from IPF patients. The results indicated that TF levels in BAL supernatant fluids
      from IPF patients were higher than those of normal subjects, especially in
      patients with progressive disease, suggesting that TF levels in the lung
      correlate with disease activity. PAI-1 levels in BAL supernatant fluids were
      significantly higher in IPF patients than in normal subjects (1.7 +/- 4.1 vs 0
      ng/mg protein). PAI-2 levels in BAL cell lysates were also significantly higher
      in IPF patients than those in normal subjects (14.4 +/- 12.2 vs 3.0 +/- 3.0 ng/mg
      protein). However, u-PA levels in both BAL supernatant fluids and BAL cell
      lysates did not differ between the two groups. These observations suggest that u
      PA inhibition exceeded u-PA activity in alveolar lining fluid resulting in an
      antifibrinolytic condition. Immunohistochemical analysis showed that TF was
      intensely stained in cuboidal epithelial cells and PAIs were positively stained
      in alveolar macrophages (AMs) and cuboidal epithelial cells, suggesting that
      cuboidal epithelial cells as well as AMs contribute to the increased procoagulant
      and antifibrinolytic activities in the lungs of IPF patients.

PMID- 7624836
TI  - Arterial antithrombotic effect of piyavit, the novel pharmacological preparation
      from the medicinal leech, and of its components, prostanoids and enzyme
      destabilase.
AB  - Piyavit, the novel pharmacological preparation from the medicinal leech (Hirudo
      medicinalis) contained the leech saliva, produces the potent arterial
      antithrombotic effect examined on experimental of Laser Induced Thrombus
      formation. Administrated orally into rats or injected subcutaneously as water
      extract, non-diluted or in 1600 times diluted, it inhibits statistically
      significant comparing with control platelet thrombus stimulated by laser beams.
      Its components, prostanoid fraction and purified enzyme destabilase, endo-epsilon
      (gamma-Glu)-Lys-isopeptidase, also inhibit thrombus formation in statistically
      different manner, comparing with control. All the tested preparations inhibit
      platelet aggregation induced by ADP. The dependence of arterial antithrombotic
      effect on the leech prostanoid is discussed.

PMID- 7624838
TI  - Influence of hormones on platelet intracellular calcium.
AB  - The pathophysiology of thromboembolic disease associated with estrogen therapy is
      poorly understood. There are innumerable calcium-dependent activities involved in
      platelet function. To determine whether platelet calcium levels are affected by
      exogenous hormones, intracellular calcium and release were studied in platelets
      in various hormonal environments and findings were correlated with platelet
      adhesion and aggregation. Platelet intracellular calcium concentration and
      release was significantly decreased in women ingesting tamoxifen compared to
      controls and significantly increased, as was platelet adhesion, in oral
      contraceptive users. Platelets incubated ex vivo with estradiol had increased
      intracellular calcium and release but there was decreased adhesion to
      fibronectin. Intracellular calcium concentration and release were not affected
      when platelets were incubated with tamoxifen. Adhesion to collagen III was
      increased in tamoxifen-incubated platelets. Only oral contraceptive users had
      increased sensitivity to aggregating agents. This data suggests that 17 beta
      estradiol, progesterone, and tamoxifen likely have a nongenomic effect on
      platelet intracellular calcium and calcium release and that platelet calcium
      levels are closely related to the degree of platelet adhesion and aggregation in
      vivo.

PMID- 7624839
TI  - Chloroquine inhibits stimulated platelets at the arachidonic acid pathway.
AB  - Chloroquine inhibited arachidonic acid liberation from membrane phospholipids of
      thrombin- and A23187- stimulated platelets. In addition, it dose-dependently
      inhibited stimulated malondialdehyde formation and thromboxane B2 generation in
      the same platelets. The linear correlation between the inhibition of arachidonic
      acid liberation and malondialdehyde formation indicated that chloroquine
      inhibited activated phospholipase A2 in thrombin-stimulated platelets, similarly
      as it does in different cells and tissues. Yet, the nonlinear relationship
      between arachidonic acid liberation along with malondialdehyde formation and
      thromboxane generation as well as aggregation suggest that phospholipase A2 does
      not seem to be the only site of chloroquine action. Rather, it may affect
      platelets either at other levels of the arachidonic acid cascade too, or at some
      different stimulatory pathways, like intraplatelet calcium mobilisation,
      phosphoinositide cycle, calmodulin and protein kinase C activation.

PMID- 7624840
TI  - Platelet GPIIb/IIIa receptor occupancy studies using a novel fluoresceinated
      cyclic Arg-Gly-Asp peptide.
AB  - DMP 728 is a potent and specific platelet GPIIb/IIIa antagonist. Like all
      GPIIb/IIIa antagonists, DMP 728 has a steep dose-response relationship in
      inhibiting platelet aggregation. In this study the relationships between receptor
      occupancy, platelet aggregation and bleeding time was determined in anesthetized
      dogs after intravenous infusion of DMP 728 (0.01 and 0.1 mg/kg/2h). Receptor
      occupancy was determined by flow cytometry using XL086, a novel fluorescent
      cyclic RGD peptide that binds to GPIIb/IIIa with high specificity and affinity
      (kd approximately 55 nM). Mean number of GPIIb/IIIa as determined by flow
      cytometric assay was approximately 53,8000 and 79,000 on unactivated and ADP
      activated platelets respectively. After DMP 728 intravenous infusion, there was a
      dose- and time-dependent increase in receptor occupancy, inhibition of platelet
      aggregation and bleeding time. The two methods of receptor occupancy
      determination correlate with each other with an r2 = 0.78. The present data
      suggest that blockade of only 40-60% (approximately 40,000 receptors) of the
      total platelet GPIIb/IIIa was required to achieve > 90% inhibition of platelet
      aggregation and > 15 min bleeding time. Our results showed the potential clinical
      utility of this approach in the study of GPIIb/IIIa dose-response relationship.

PMID- 7624841
TI  - Plasma concentration of tissue factor and factor VII in patients after abdominal
      surgery.
AB  - Tissue injury following trauma and surgery may induce alterations in blood
      coagulation and fibrinolysis. Hypercoagulable state after surgery can be
      associated with the risk of postoperative thromboembolic complications. The
      contact of coagulation factors with TF after injury of vessel wall and organ
      tissues may contribute to the development of thrombosis after surgery (1). TF,
      the cell surface receptor and cofactor of factor VII/VIIa is normally not
      expressed by cells within the vasculature. Only monocytes and endothelial cells
      can be stimulated to express TF transiently by a variety of inflammatory and
      immunological reactions (for review see 2,3). Also surgical treatment was
      reported to induce TF synthesis in monocytes (4,5,6). TF is present in many
      extravascular tissues as vascular adventitia, organ capsules, epidermis, colonic
      mucosal epithelium, liver stroma, pancreas stroma and also on tumor cells (7-12).
      In this study, we investigated, whether we can detect the release of TF from the
      traumatized tissues and from activated monocytes into the circulation following
      abdominal surgery. To test the dependence of the extension of tissue injury
      during surgery we segregated the patients into group A with major abdominal
      operations and group B consisting of patients with appendectomy and
      cholecystectomy. No relationship could be established between changes of TF and
      postoperative thromboembolic complications.

PMID- 7624842
TI  - Evaluation of the new method Coaguchek for the determination of prothrombin time
      from capillary blood: comparison with Thrombotest on KC-1.

PMID- 7624843
TI  - [Reliability of bacteriological studies of composite samples in the diagnosis of
      subclinical udder infections in cattle].
AB  - This study evaluated the reliability of making bacteriological cultures of
      composite milk samples for the diagnosis of subclinical udder infections in dairy
      herds. Quarter samples as well as composite samples were collected from 482 cows
      with suspected subclinical mastitis from 69 Dutch dairy farms. The samples were
      used to measured somatic cell counts and to prepare bacteriological cultures. The
      sensitivity and specificity of the bacteriological cultures of the composite
      samples were compared with those of the quarter samples. The sensitivity of
      Staphylococcus aureus, Streptococcus uberis, Streptococcus agalactiae and
      Streptococcus dysgalactiae was 57.9%, 65.2%, 86.6%, and 60.3%, respectively. The
      specificity was higher than 98% for all four bacteria. Although information is
      lost when composite samples are used, composite samples are useful, especially
      for large dairy herds. The advantage and disadvantages of the use of composite
      samples are discussed.

PMID- 7624844
TI  - [Treatment of multiple metacarpal (tarsal) fractures using a brace in 2 foals and
      a calf].
AB  - The placement of a brace for external fixation of multiple fractures of the
      carpus or tarsus is described. In these two foals and calf we succeeded in
      obtaining a combination of good immobilization and full loading of the affected
      leg.

PMID- 7624845
TI  - [An overview of veterinary medicine from 1960 to today with a look toward the
      future].

PMID- 7624846
TI  - [Abomasum dislocations].

PMID- 7624847
TI  - [Quality guidelines for veterinary practice].

PMID- 7624848
TI  - [Tooth problems in guinea pigs].

PMID- 7624849
TI  - [Ultrasonography in veterinary ophthalmology].
AB  - Ophthalmic examination evaluates ocular structures in both the anterior and the
      posterior segments of the eye. In the eye without opacities of the transmitting
      media, this is accomplished through biomicroscopy, direct and indirect
      ophthalmoscopy. However, in eyes with media opacities, evaluation, especially of
      the posterior segment, is difficult or impossible by these routine methods.
      Further, evaluation of retrobulbar tissues has been limited to radiography and
      blind aspirate, or surgical exploration. Ultrasound is a noninvasive, safe
      procedure that allows evaluation of the intraocular and retrobulbar tissues
      without sedation or general anesthesia.

PMID- 7624850
TI  - [Clinical case. A Hannover gelding, 15 years old, jumping horse].

PMID- 7624851
TI  - [Insertion of fine needle biopsy in the diagnosis of nocardia mastitis in
      cattle].
AB  - 68 udder quarters of 31 cows suspicious of acute or chronic nocardia mastitis
      were investigated by fine needle aspiration biopsy (FNA) of udder tissue and by
      bacteriological examination (BE) of milk samples. The results were compared.
      Nocardia mastitis was diagnosed in seven cows with corresponding cytological and
      bacteriological findings, in four cows with positive FNA and negative BE, and in
      nine cows with negative FNA and positive BE. In eleven animals nocardia mastitis
      was diagnosed neither cytologically nor bacteriologically. In some of these
      cases, however, mastitis could be attributed to other pathogens (streptococci,
      staphylococci, fungi). The FNA is recommended as an additional tool for mastitis
      diagnosis.

PMID- 7624852
TI  - [Epidermolysis bullosa in a calf].
AB  - A four-week-old Simmental x Red Holstein calf had lesions of skin and oral mucosa
      since its first days of life. Where skin or mucosa was exposed to minimal trauma
      as in oral cavity or over joints, it broke off, forming blisters and erosions.
      The diagnosis of epidermolysis bullosa, a hereditary disease, was based on
      clinical and histological findings. Histology pointed to the epidermal form of
      epidermolysis bullosa, comparable to epidermolysis bullosa simplex in humans.

PMID- 7624853
TI  - [Psoroptic scab control in sheep herds--experiences in use of medications].
AB  - Due to an uncontrolled trade in sheep, the importance of sheep scab has increased
      recently. Alone in Thuringia six outbreaks occurred in 1993. Now psoroptic mange
      is endemic in Germany. Mutual infections between sheep and cattle seem to be
      extremely rare in the field. Outbreaks of sheep scab entails heavy economic
      losses. Therefore, control has to be successful and to aim at eradication. The
      survivability of the psoroptic mites aside from the host until 48 days has to be
      considered. Eradication can be achieved, as proved by own field trials for a
      period of 10 months only either by two repeated dipping using Phoxim or HCH drugs
      or by subcutaneous Ivermectin injections (0.2 mg/kg bodyweight) seven days apart.
      The success of treatment has to be checked carefully.

PMID- 7624854
TI  - [Gynecologic laparoscopy in sheep. 2. Applications].
AB  - The gynaecological laparoscopy is basical for the correct diagnosis of the
      ovaries and the uterus in sheep. Physiological (follicles, corpora lutea) and
      pathological findings (follicle cysts) are described and illustrated. Further,
      application techniques of the laparoscopic intrauterine insemination as well as
      of the embryo recovery and embryo transfer in embryo transfer programs are
      explained.

PMID- 7624855
TI  - [Vesical flexion and vaginal prolapse of sows as an obstetrical problem].
AB  - The evaluation of 523 clinically supervised parturitions of swine from the last
      ten years showed that vesical flexion and vaginal prolapse as a complex range
      together (with 9.4%) on place three of the causes of dystocia. There were 16
      cases of vesical flexion (= 3.1% of dystocia) and 33 cases of vaginal prolapse (=
      6.3% of dystocia). Both groups showed a lot of mutualities. For example most
      cases in both groups were shortly before the third parturition. 50% of vesical
      flexions and 78.8% of vaginal prolapses appeared within one week before
      parturition concerning the third pregnancy in 25 and 27.3% of the cases. Both
      kinds of illness often were accompanied by a further dislocation of rectal
      tissue. This concerned 31.2% of the patients with vesical flexion and 21.2% of
      those with vaginal prolapse. The patients in 81.2% of vesical flexions and in
      72.7% of vaginal prolapses were not taken to the clinic before dislocation of
      tissue appeared stationary. To make sure the diagnosis "vesical flexion" and to
      differentiate it from vaginal prolapse several methods are available. The most
      important one is catheterization of the bladder. This was done in 56.2% of the
      cases for diagnostical as well as for therapeutical reasons. To avoid relapses
      the foley-catheter had to be left in the bladder for maximal 19 days and for 6
      days on an average. The vaginal prolapse after reposition was treated in 60.6% of
      the cases by a vaginal fastening. This was done to 75% of these patients
      according to Buhner.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7624856
TI  - [Susceptibility of bacterial isolates from the equine respiratory tract to
      trimethoprim, sulfadoxine, sulfadimethoxine and combinations of these compounds].
AB  - Using a broth microdilution technique, the in vitro susceptibility of bacterial
      isolates from the equine respiratory tract to trimethoprim, sulfadoxine,
      sulfadimethoxine, and combinations of these compounds was determined. The
      bacterial strains (n = 88) isolated recently from horses with respiratory
      symptoms belonged to the following species: Streptococcus equi subsp.
      zooepidemicus (n = 34), Streptococcus equi subsp. equi (n = 22), Staphylococcus
      aureus (n = 9), Klebsiella pneumoniae (n = 7), Rhodococcus equi (n = 4),
      Pseudomonas spp. (n = 3) and Escherichia coli (n = 3). In addition, two isolates
      of Enterobacter spp. and one isolate of Streptococcus equisimilis, Staphylococcus
      intermedius, Proteus mirabilis and Serratia marcescens were examined. For
      determination of susceptibility of an organism the following minimal inhibitory
      concentrations (MIC) were fixed as limiting values: Trimethoprim < or = 0.5
      microgram/ml, sulfadoxine < or = 32 micrograms/ml, sulfadimethoxine < or = 32
      micrograms/ml, trimethoprim/sulfadoxine < or = 0.5/32 micrograms/ml,
      trimethoprim/sulfadimethoxine < or = 0.5/32 micrograms/ml. As expected,
      Rhodococcus-equi-isolates were resistant to the antimicrobials tested. However,
      most of the clinically more common isolates showed a high degree of
      susceptibility to the combinations. The fractional inhibitory concentration (FIC)
      indices indicated synergism of the combination-partners in a wide range.
      According to these in vitro results, application of trimethoprim/sulfonamide
      combinations for the initial therapy of equine respiratory tract infections can
      be recommended.

PMID- 7624857
TI  - [Glycosylated hemoglobin in the cat: affinity chromatography determination in
      healty, permanent diabetes mellitus and transient hyperglycemic cats].
AB  - The affinity method has proved to be the first technique that succeeded in
      measuring feline GHb as it is not affected by structural differences of
      haemoglobin as traditional proceedings are. By its help the reference interval
      for feline GHb was established from blood samples of 62 healthy cats. It ranged
      between 0.31 to 1.58% with a median of 0.92%. 21 newly diagnosed diabetic cats
      were reliably determined to be diabetic, because the GHb exceeded significantly
      the upper limit of the reference interval of 1.30%. The statistical difference
      between diabetic and healthy cats was highly significant (p < 0.00001). It was
      confirmed that the GHb value helps to distinguish diabetic from transient
      hyperglycemic cats. Newly presented hyperglycemic cats suffer from diabetes
      mellitus, if their GHb values are increased (p < 0.00001).

PMID- 7624858
TI  - [Therapy of narrow canine teeth using a methacrylate orthodontic splint].
AB  - 32 cases of narrow canine teeth were treated with an orthodontic splint similar
      to the Becker-splint (1965). The splints are either fixed only to one or two
      teeth using adhesive bone of to both canine teeth and incisors. They can be made
      simply within short time and may treat different orthodontic problems.

PMID- 7624859
TI  - [Hypokalemic myopathy in cats].
AB  - Clinical signs, laboratory findings and the course of hypokalemic myopathy in ten
      cats are described. One of these cats needed continuing potassium substitution;
      in the other nine cats hypokalemia was a temporary phenomenon as a result of
      severe diabetic ketoacidosis and its therapy. In these patients normokalemia was
      achieved after potassium substitution for three to seven days. The clinical signs
      of hypokalemic myopathy already resolved after one to four days. Etiologic
      factors contributing to hypokalemic myopathy in these patients are discussed.

PMID- 7624860
TI  - [Mast cell tumors in dogs--diagnosis and therapy of a malignant skin tumor].
AB  - The high prevalence of mast cell tumors in dogs and their variable presentation
      make this neoplasia a diagnostic and therapeutic challenge for the small animal
      practitioner. Classification of the tumor according to histologic grade and
      clinical stage of the disease is important for therapy and prognosis. Surgical
      excision and chemotherapy are discussed for individual tumor grades and stages.

PMID- 7624861
TI  - [Behavior of Orf virus in permissive and nonpermissive systems].
AB  - Dogs were immunized i.m. with attenuated poxvirus vaccines (vaccinia virus, Orf
      virus) and a bovine herpesvirus-1 (BHV-1) vaccine. After intradermal (i.d.)
      application of the vaccine viruses a specific delayed type hypersensitivity (DTH)
      reaction of the skin occurred only with vaccinia virus. The i.d. application of
      Orf-virus caused a short-term, non-specific inflammatory reaction of the skin,
      even in dogs not immunized with Orf-virus. Out of 30 sera from Orf-virus
      immunized beagles (n = 4) only eight were found reactive to Orf-virus in a
      competition ELISA. Three sera from dogs not Orf-virus immunized but skin-tested
      with the virus contained low antibody titers. Using indirect immunofluorescence
      (IIF) in flow cytometry, the existence of Orf-virus antigens was examined on the
      surface and in the cytoplasm of permissive (BFK and Vero)- and questionable
      permissive MDCK cells. The canine kidney MDCK cell line was found to be non
      permissive for Orf-virus replication; the occurrence of an Orf-(ecthyma
      contagiosum) like disease in dogs is unlikely.

PMID- 7624862
TI  - [Case report: effect of maternal antibodies on the vaccination against canine
      parvovirus].
AB  - The problem of vaccination against canine parvovirosis is discussed. In this case
      study the antibody titers against canine parvovirus were determined in a
      vaccinated bitch and her puppies and the accuracy of the estimation for the best
      time of vaccination is commented.

PMID- 7624863
TI  - [Blood parameters and enzyme values of healthy and sick racing camels (Camelus
      dromedarius)].
AB  - Camel races have a long tradition in Arabia. Since the oil boom of the 1960s a
      tremendous revival of the old Bedouin tradition of camel racing has occurred in
      the United Arab Emirates. These camel races are comparable to horse races in
      Europe and the U.S.A. Since 1985 the most valuable racing camels of Dubai are
      routinely tested in the Central Veterinary Research Laboratory (CVRL) for their
      stamina and endurance. Blood and serum enzyme values, which have been
      statistically ascertained through testing of 10000 healthy racing camels, are now
      generally accepted as reference values. Besides these check-ups of healthy racing
      camels, hematological tests, enzyme and substrate estimations are performed on
      sick racing camels. These tests support the diagnosis, therapy and prognosis of
      sick camels. In this connection three diseases are discussed: B. cereus
      intoxication, Clostridium perfringens enterotoxemia and Trypanosomiasis.

PMID- 7624864
TI  - [Cytology of body cavity effusions].
AB  - The cytological examination of body cavity effusions is a fast and technically
      simple procedure. The specificity of the method to diagnose a malignoma is high,
      and the sensitivity is sufficient. Round cell sarcomas and carcinomas exfoliate
      well, but other sarcomas can rarely be diagnosed cytologically in the body
      effusion. Inflammation and bacterial or mycotic infection of the hydrops are
      evident. Cytological examinations of body effusions of other etiologies are not
      so specific.

PMID- 7624865
TI  - Comparison of tissue retention of aluminum and Ga-67: effects of iron status in
      rats.
AB  - The purposes of this study were to separate the effect of iron status from the
      effect of acute iron intake on tissue retention of aluminum and Ga-67 and to
      evaluate Ga-67 as a marker for aluminum. Anemic and control rats were dosed by
      gavage with a citrate solution containing 20 microCi Ga-67 with no added aluminum
      and iron (Gavage Ga-67), with 0.8 mmol aluminum (Gavage Al), with 0.8 mmol iron
      (Gavage Fe), or with both 0.8 mmol aluminum and 0.8 mmol iron (Gavage Fe and Al).
      After 24 h, anemic rats in the Gavage Al treatment had lower concentrations of
      aluminum in their tibias, kidneys, and spleens than control rats in that
      treatment. In contrast, anemic rats dosed with only Ga-67 (Gavage Ga-67
      treatment) had lower concentrations of Ga-67 in their tibias and kidneys, but
      greater concentrations of Ga-67 in their livers and spleens than control rats in
      that treatment. The single dose of iron had no effect on tissue aluminum
      concentrations but depressed tissue Ga-67 concentrations. All rats accumulated
      aluminum predominantly in bone and control rats accumulated Ga-67 predominantly
      in bone, but anemic rats accumulated Ga-67 predominantly in liver. A major
      limitation of Ga-67 as a marker for aluminum is its greater sensitivity than
      aluminum to iron intake and status.

PMID- 7624866
TI  - Impairment of testicular endocrine function after lead intoxication in the adult
      rat.
AB  - To clarify the mechanism of the action of lead on male reproductive function,
      adult male rats were injected intraperitoneally (i.p.) with lead acetate (8
      mg/kg/day of lead), 5 days a week for 35 days. Despite this high dose, germ cells
      and Sertoli cells did not appear to be major targets of lead. However, lead
      determination in the reproductive organs showed that the accessory sex glands are
      such a target. Epididymal function was unchanged. In lead-exposed rats, plasma
      and testicular testosterone dropped by about 80%, but plasma luteinizing hormone
      (LH) only dropped by 32%. After luteinizing hormone releasing hormone (LHRH)
      stimulation of the pituitary, the plasma LH level reached the control one, but
      plasma testosterone remained significantly reduced by 37%. The sharp decrease in
      the testosterone:LH ratio in lead-exposed rats, combined with the significant
      reduction of intertubular tissue volume in the testes, indicate impaired Leydig
      cell function.

PMID- 7624867
TI  - Cephaloridine nephrotoxicity in diabetic rats: modulation by insulin treatment.
AB  - Previous studies have indicated that cephaloridine nephrotoxicity was reduced in
      diabetic rats. This study determined whether the reduction in toxicity was due to
      streptozotocin or the diabetic state. Male Fischer-344 rats were injected
      intraperitoneally with 35 mg/kg streptozotocin to induce diabetes. Insulin (5
      U/day, subcutaneously) was begun within 72 h and continued for 10 days. Toxicity
      was quantitated 48 h after injection of cephaloridine (1500 mg/kg, i.p.) in
      normoglycemic (NC), diabetic (DC) and diabetic animals treated with insulin
      (DIC). Cephaloridine produced diuresis, glucosuria, proteinuria, elevated kidney
      weight and decreased renal cortical slice accumulation of organic ions in the NC
      group. Cephaloridine toxicity was reduced in the DC group since kidney weight,
      BUN level and renal cortical slice accumulation of organic anions were similar
      between treated and control animals. Cephaloridine treatment of the DIC group was
      associated with increased BUN levels, proteinuria and diminished renal cortical
      slice accumulation of organic cations. These results indicated that the diabetic
      state, and not streptozotocin, reduced cephaloridine nephrotoxicity.

PMID- 7624868
TI  - Release of prostaglandin E2 and leukotriene C4/D4 from airway segments isolated
      from rats after exposure to ozone for 20 months.
AB  - Metabolites of arachidonic acid have been implicated as mediators of some of the
      pulmonary effects observed after acute exposure to ozone. Accordingly, recent
      studies have focused on the effects of acute ozone exposure on the arachidonic
      acid cascade, however, whether eicosanoid metabolism is altered after chronic
      exposure to ozone is unknown. To begin to address this issue, we examined the
      effects of near-lifetime exposure to ozone on release of prostaglandin E2 (PGE2)
      and leukotriene C4/D4 from airway segments isolated from exposed Fischer-344
      rats. Airway segments representing approximately eighth to tenth generation
      airways were isolated from rats of both genders that had been exposed for 6 h per
      day, 5 days per week for 20 months to filtered air or 0.12, 0.5 or 1.0 parts per
      million (ppm) ozone. Basal and stimulated release of eicosanoids were measured in
      the medium surrounding airway segments using enzymoimmunoassay. Basal release of
      PGE2 was detected in the medium surrounding airway segments and this release was
      unaffected by ozone exposure. Incubation of the segments with the calcium
      ionophore, A23187, increased the release of the prostaglandin; the A23187-induced
      release of PGE2 was significantly enhanced in airway segments isolated from rats
      in the 1.0 ppm exposure group. Basal release of leukotriene C4/D4 was not
      detected in the medium surrounding airway segments regardless of ozone exposure.
      Measurable amounts of the leukotriene were released during incubation with
      A23187, however, ozone was without affect on these levels. The results suggest
      that the cyclooxygenase pathway of the arachidonic acid cascade appears to be
      affected by ozone exposure. Which of the processes of prostaglandin production
      and release are affected by chronic ozone exposure remains to be determined.

PMID- 7624869
TI  - Altered enzyme activities of xenobiotic biotransformation in kidneys after
      subchronic administration of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone
      (MX) to rats.
AB  - Activities of the xenobiotic metabolizing enzymes were measured in the liver,
      kidney, duodenum and lung microsomes and cytosol fractions of Wistar rats after
      subchronic administration of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone
      (MX), a potent bacterial mutagen in chlorinated drinking water. MX was
      administered by gavage at the dose level of 30 mg/kg for 18 weeks (low dose), or
      at the dose level which was raised gradually from 45 mg/kg for 7 weeks via 60
      mg/kg for 2 weeks to a clearly toxic dose of 75 mg/kg for 5 weeks (high dose).
      Microsomal and cytosolic preparations were made and the activities of 7
      ethoxyresorufin-O-deethylase (EROD), pentoxyresorufin-O-dealkylase (PROD), NADPH
      cytochrome-c-reductase, UDP-glucuronosyltransferase (UDPGT) and glutathione-S
      transferase (GST) were measured. Kidneys were affected most. A dose-dependent
      decrease was observed in EROD (90% in males, 80% in females at the high dose) and
      in PROD (58% in females at the high dose) in kidneys. An increase was, however,
      detected in kidney NADPH-cytochrome-c-reductase (66% in females at high dose),
      UDPGT (89% in males and 97% in females at high dose) and GST activities (56% in
      males and 50% in females at high dose). MX caused only a few changes in the
      enzyme activities of the liver. The EROD activity was decreased 25% to 37%, both
      in the livers of males and females, but the total content of P450s was not
      altered. Hepatic GST activity was elevated in females in a dose-dependent manner
      (31% and 44%). GST activity was elevated in duodenum in females (59%) at the high
      dose. There were no marked changes in the enzyme activities in the lungs. MX was
      a weak inhibitor of EROD activity both in the liver and kidney microsomes in
      vitro, decreasing the EROD activity by 53% and 43%, respectively at the
      concentration of 0.9 mM. The results indicate that MX decreases the activity of
      phase I metabolism enzymes, but induces phase II conjugation enzyme activities,
      particularly in kidneys in vivo. It is possible that these changes contribute to
      metabolism of MX in kidneys and renders them susceptible to MX in the course of
      repeated exposure.

PMID- 7624870
TI  - A protein kinase C inhibitor attenuates cyanide toxicity in vivo.
AB  - We have examined the effect of pretreatment with a potent protein kinase C (PKC)
      inhibitor, 1-(5-isoquinoline-sulfonyl)-2-methylpiperazine (H-7), against
      metabolic alterations induced by sodium cyanide (NaCN), 4.2 mg/kg, in brain of
      anesthetized male micropigs (6-10 kg). Brain high energy phosphates were analyzed
      using a 31P nuclear magnetic resonance (NMR) spectroscopic surface coil in a 4.7
      Telsa horizontal bore magnet. H-7, 1 mg/kg, was given intravenously (i.v.) 30 min
      before NaCN challenge (H-7 + CN-). Prior to NaCN, H-7, or H-7 + CN-
      administration, baseline 31P resonance spectra of 1-min duration were acquired
      for 5-10 min, and continued for an additional 60 min following i.v. NaCN
      injection, each animal serving as its own control. Peaks were identified as
      phosphomonoester (PME), inorganic phosphate (Pi), phosphodiester (PDE),
      phosphocreatine (PCr) and adenosine triphosphate (ATP), based on their respective
      chemical shifts. Without H-7 pretreatment, NaCN effects were marked by a rising
      Pi and a declining PCr peak 2 min after injection, with only 2/5 of the animals
      surviving the 60 min experiment. Through a pretreatment period of 30 min, H-7 did
      not affect baseline cell energy profile as reflected by the 31P-NMR spectra, but
      in its presence, those changes (i.e. diminishing PCr and rising Pi peaks)
      elicited by NaCN were markedly blunted; 4/5 of the animals in this group survived
      the NaCN challenge. It is proposed that H-7, a pharmacologic inhibitor of PKC,
      may be useful in CN- antagonism, underscoring the role of PKC in cyanide
      intoxication.

PMID- 7624872
TI  - Toxicity, metabolism and absorption of selenite by isolated rat hepatocytes.
AB  - The uptake of various levels of selenite by isolated rat hepatocytes was
      investigated. The LD50 value of selenite was about 500 microM. The activity of
      lactic dehydrogenase in the medium was correlated with cell viability as
      determined by trypan blue exclusion. After incubation of selenite with
      hepatocytes, protein-bound Se was the predominant form (80-90% of the cellular
      Se) present. Subcellular fractionation indicated that most of the radioactivity
      was present in the cytosol when hepatocytes were incubated with 75Se-selenite.
      The uptake of 75Se by isolated rat hepatocytes was linear with selenite
      concentration up to the highest amount tested, 200 microM. Sulfite inhibited the
      uptake of selenite by hepatocytes.

PMID- 7624871
TI  - Leukotrienes and alpha-naphthylisothiocyanate-induced liver injury.
AB  - alpha-naphthylisothiocyanate (ANIT) administration to rats results in periportal
      hepatic inflammation and injury. Glutathione (GSH) appears to be necessary for
      the liver injury to occur. The leukotrienes (LTs) are metabolites of arachidonic
      acid and potent mediators of inflammation that have been implicated in certain
      liver injury models. Inasmuch as GSH is a cofactor for the synthesis of cysteinyl
      LTs and since inflammation is a prominent component of ANIT injury, we
      hypothesized that LTs are involved in producing the hepatic insult that results
      from ANIT administration. To test this hypothesis, rats were treated with one of
      several inhibitors of LT biosynthesis, A63162, Zileuton or MK-886. Each of these
      agents prevented the formation of LTB4 in Ca++ ionophore-stimulated whole blood
      from rats treated with the inhibitors. A63162 attenuated the hepatic parenchymal
      injury caused by ANIT and resulted in a modest decrease in ANIT-induced
      cholestasis. In contrast, neither Zileuton nor MK-886 attenuated liver injury. AT
      125 (Acivicin) inhibits gamma-glutamyl transferase (GGT), the enzyme that
      catalyzes the formation of LTD4 from LTC4. AT-125 pretreatment did not prevent
      ANIT-induced hepatic parenchymal insult. It did, however, ameliorate the
      cholestasis caused by ANIT. In conclusion, the partial protection afforded by
      A63162 and AT-125 likely results from effects unrelated to the formation of LTs,
      since Zileuton and MK-886 inhibited LT synthesis without affording protection.
      The lack of protection by Zileuton and MK-886 in the face of LT synthesis
      inhibition suggests that LTs are not necessary for the expression of injury after
      ANIT administration.

PMID- 7624873
TI  - Effects of exposure to environmental tobacco smoke on a human tracheobronchial
      epithelial cell line.
AB  - BEAS-2B cells, a human bronchial epithelial line immortalized by viral
      transformation, were exposed to sidestream tobacco smoke (STS) as a surrogate for
      environmental tobacco smoke (ETS) under biphasic culture conditions where the
      apical portion of the cells was in direct contact with the gas phase. Dose
      dependent cytotoxicity was observed. In addition, induction of an as yet
      uncharacterized protein of molecular weight 45,000 was associated with exposure
      to STS. This protein might be part of a protective response of exposed cells,
      which do not show a classical heat shock response when exposed to STS. We
      conclude that STS and ETS can be directly cytotoxic to human airway epithelial
      cells in biphasic culture at concentrations not unreasonable for smoky indoor
      atmospheres. The model system described in this paper should be useful for
      studying the detailed mechanisms of cytotoxicity of, and protection from, ETS
      exposure in the human cells most directly exposed to ETS in vivo.

PMID- 7624874
TI  - The dose-dependent inhibition of rat renal translation elongation seen after in
      vivo cyclosporin A is not caused by cyclosporin metabolites.
AB  - Cyclosporin A (CsA) given to Sprague-Dawley rats in vivo produced a tissue
      specific, dose-dependent inhibition of translation elongation in renal
      microsomes. CsA at an oral dose of 50 mg/kg/day for 6 days reduced renal
      microsomal translation by 70.5%. Renal cytoplasm from rats treated in vivo with
      CsA inhibited translation by 55% when added to renal microsomes isolated from
      tissues of control animals. In contrast, CsA added to renal microsomes in vitro
      did not inhibit translation. Renal cytoplasm from CsA-treated rats containing
      translation inhibitory factor was found by HPLC to contain CsA and CsA
      metabolites M1 and M17. CsA metabolites M1, M17, M18 and M21 were isolated from
      human bile and tested in vitro for translation elongation inhibitory activity in
      renal microsomes. CsA, M18 and M21 did not inhibit translation elongation at
      concentrations of up to 2500 ng/ml. M17 inhibited translation elongation, but
      only by 8.4% at the highest concentration tested (2500 ng/ml), a level 20-fold
      higher than that measured in renal cytoplasm (125 ng/ml). M1 produced a
      concentration-dependent inhibition of translation elongation, beginning at 500
      ng/ml, or approximately 2-fold higher than that found in renal cytoplasm (260
      ng/ml). M1 at 2500 ng/ml or approximately 10-fold higher than the concentration
      measured in renal cytoplasm, inhibited translation elongation by 23.8%, only 1/3
      that observed upon addition of renal cytoplasm containing translation inhibitory
      factor. We conclude from these findings that the dose-dependent inhibition of
      renal translation elongation following in vivo CsA cannot be explained by the
      renal formation or uptake of known CsA metabolites.

PMID- 7624875
TI  - Suicidal inactivation of haemoproteins by reductive metabolites of halomethanes:
      a structure-activity relationship study.
AB  - Human haemoglobin (Hb), methaemalbumin (MHA) or rat liver microsomal cytochrome P
      450 (P-450) were incubated anaerobically at microM concentrations with 1 mM
      carbon tetrachloride (CCl4), trichlorobromomethane (CCl3Br), chloroform (CHCl3)
      or methylene chloride (CH2Cl2) in presence of 1 mM sodium dithionite as the
      reducing agent. At the end of a 5-min incubation, haem was measured by various
      methods, i.e. binding spectrum with CO, pyridine-haemochromogen haem assay and
      porphyrin fluorescence, and compared for the four analogues. Statistically
      significant losses were observed, with all three haemo-protein systems, for
      CCi3Br, CCl4 and CHCl3, but not CH2Cl2. For Hb, the loss was greater with CCl3Br
      (haem assay, 63%; porphyrin fluorescence, 48%; CO binding, 24%) than with CCl4
      (haem assay, 31%) or CHCl3 (haem assay, 13%). On the other hand, with MHA, CCl4
      gave a dramatic loss (haem assay, 88%; porphyrin fluorescence, 83%; CO binding,
      67%), which was greater than that observed with CCl3Br (haem assay, 49%;
      porphyrin fluorescence, 38%; CO binding, 25%). No loss was found with CHCl3.
      Finally, with microsomes, the inactivation was larger with CCl4 (CO binding, 58%;
      haem assay, 50%; porphyrin fluorescence, 33%) than with CCl3Br (CO binding, 33%;
      haem assay, 10%) or CHCl3 (haem assay, 9%; CO binding, 6%). In a separate set of
      similar experiments, an ion-pairing reverse phase HPLC method showed the
      formation of substrate-dependent hae-derived products during incubation of CCl3Br
      with Hb or microsomes, and of CCl4 with Hb. A correlation between potential for
      free radical formation (CCl3Br > CCl4 > CHCl3 > CH2Cl2) and extent of haem
      inactivation was observed with all methods for Hb, but not for microsomal P-450
      or MHA. The results indicate that these halomethanes may be activated differently
      by different haemoproteins and suggest that their potential ability to undergo
      reductive metabolism may not be the only critical factor involved in P-450 haem
      inactivation by these chemicals.

PMID- 7624876
TI  - Persistent, specific and dose-dependent effects of toluene exposure on dopamine
      D2 agonist binding in the rat caudate-putamen.
AB  - Exposure to toluene (40-320 ppm; 4 weeks, 6 h/day, 5 days/week), followed by a
      postexposure period of 29-40 days, decreased the wet weight of the caudate
      putamen and of the subcortical limbic area (maximal effect of 10% attained at 80
      ppm toluene) of the male rat. Furthermore, toluene exposure decreased the IC50
      values (significant effects attained at 80 ppm), the KH, the KL, and the RH%
      values of dopamine on [3H]raclopride-binding in the caudate-putamen. Toluene
      exposure did not significantly affect either the body weights, the wet weights of
      the whole brain, the serum prolactin levels, the KD or the Bmax values of
      [3H]raclopride-binding in the caudate-putamen and the subcortical limbic area, or
      the IC50 values of dopamine at [3H]raclopride-binding sites in the subcortical
      limbic area. Exposure to xylene or styrene (80 and 40 ppm, respectively; 4 weeks,
      6 h/day, 5 days/week), followed by a postexposure period of 26-32 days, had no
      effect on the parameters described above (prolactin levels were not analyzed).
      The present study indicates that long-term exposure to low concentrations of
      toluene (> or = 80 ppm), but not xylene (80 ppm) or styrene (40 ppm), leads to
      persistent increases in the affinity of dopamine D2 agonist binding in the rat
      caudate-putamen.

PMID- 7624877
TI  - The effects of N-(5-vinyl-1,3-thiazolidin-2-ylidene)phenylamine (5-VTPA) on the
      changes in free intracellular calcium and the production of reactive oxygen
      metabolites in human leukocytes.
AB  - Human leukocytes were exposed to N-(5-vinyl-1,3-thiazolidin-2-ylidene)phenylamine
      (5-VTPA), a postulated impurity in the case oils that caused the Spanish Toxic
      Oil Syndrome in 1981. Changes induced by 5-VTPA alone and together with a
      chemotactic peptide, formyl-methionyl-leucyl-phenylalanine (FMLP), a tumor
      promoter, phorbol myristate acetate (PMA), or a synthetic diacylglycerol,
      dioctanoyl-s,n-glycerol (DiC8) in free intracellular calcium levels ([Ca2+]i) and
      in the induction of oxidative burst were measured. 5-VTPA elevated dose
      dependently [Ca2+]i and induced the production of reactive oxygen metabolites in
      leukocytes. 5-VTPA also amplified FMLP-induced increase in [Ca2+]i, but was
      without an effect on FMLP-induced oxidative burst. On the contrary, 5-VTPA
      amplified dose-dependently PMA- and DiC8-induced respiratory burst. The present
      results indicate that 5-VTPA may interfere with transmembrane signalling in human
      leukocytes. 5-VTPA may elevate [Ca2+]i by acting directly on the membrane, or by
      acting through Ca(2+)-mobilizing receptors. Moreover, 5-VTPA also clearly
      amplified responses produced through protein kinase C stimulation. Thus, 5-VTPA
      may act on human leukocytes by affecting Ca(2+)-metabolism and the activity of
      protein kinase C.

PMID- 7624878
TI  - The SCID-hu mouse as a tool in immunotoxicological risk assessment: effects of 2
      acetyl-4(5)-tetrahydroxybutyl-imidazole (THI) and di-n-butyltin dichloride (DBTC)
      on the human thymus in SCID-hu mice.
AB  - SCID mice engrafted with human fetal thymus and liver tissue fragments (SCID-hu
      mice) are currently considered as a new tool in human immunotoxicological risk
      assessment. Testing of various immunotoxicants exerting thymotoxicity via
      different intrathymic target cell types is necessary for validation of this
      model. Therefore, SCID-hu mice were exposed to 2-acetyl-4(5)-(1,2,3,4
      tetrahydroxybutyl)-imidazole (THI), the immunotoxic component in the food
      additive, Caramel Colour III, or the organotin compound, di-n-butyltin dichloride
      (DBTC). Histopathological examination of the human thymus grafts of SCID-hu mice
      either exposed to THI or to DBTC showed a reduction in the relative size of the
      thymus cortex, an effect also described in rodents. These results indicate that
      the human thymus is a target for the immunotoxic action of both THI and DBTC. In
      addition, they indicate the promising potential of the SCID-hu mouse model as a
      tool for human immunotoxicological risk assessment.

PMID- 7624879
TI  - TNF-alpha production as an in vitro assay predictive of cytokine-mediated toxic
      reactions induced by monoclonal antibodies.
AB  - When administered to patients, various biotechnology products may induce early
      toxic effects mediated by a cytokine cascade in which Tumor Necrosis Factor-alpha
      (TNF-alpha) plays a central role. The mechanisms of these toxic reactions have
      been extensively documented in the clinical model of the CD3 monoclonal antibody
      (mAb), OKT3. In order to develop a preclinical test for assessing the potential
      of mAbs or recombinant molecules to induce acute reactions when administered to
      patients, we investigated different in vitro culture systems for TNF-alpha
      secretion, using human blood cells. OKT3 and bacterial lipopolysaccharide (LPS)
      were used as positive controls. By comparing different culture conditions and
      kinetics, we concluded that 6-h supernatants of plasma-depleted whole blood
      contained high amounts of TNF-alpha in cultures stimulated by OKT3 or LPS, but
      not in those performed in the absence of exogenous stimulant or in the presence
      of mAbs which do not induce toxic reactions in vivo. This in vitro assay may be
      applied to the preclinical evaluation of the risk of cytokine-mediated toxicity
      in vivo. Owing to its simplicity, it could be used for preclinical investigation
      of inter-individual differences in the susceptibility to 'activation syndrome'.

PMID- 7624880
TI  - Toxicology databases in the metadatabank of online databases.
AB  - Databases in science and technology dealing with toxicology subjects are of great
      and increasing interest to the scientific community. International hosts pay
      their tribute in creating toxicology clusters as a user-aid. Toxicology clusters
      of DataStar, DIALOG, DIMDI and STN are listed and compared. At the German
      National Research Centre for Environment and Health an 'Information System for
      Environmental Chemicals' has been developed. Within this research project
      approximately 400 online databases have been evaluated and the results are stored
      in the Metadatabank of Online Databases called DADB. A further step in this
      project is to assist the users of these metadatabases to choose the most
      appropriate database(s) for a special query. The retrieval of information out of
      a multitude of differently structured databases can be optimized using different
      evaluation criteria. We distinguished three groups of evaluation criteria: (1)
      general evaluation criteria, e.g. size of database, update frequency, cost of
      online search, etc., (2) evaluation criteria based on the characterization of
      environmental chemicals, and (3) evaluation criteria based on environmental
      relevant data-types. We studied the influence of a number of different criteria
      in order to rank a set of objects, in this particular case toxicology databases.
      We used a six-number scoring system. The scoring is carried out using the
      scientific background of lattice theory and its graphical evaluation. The
      application of this scoring system for toxicologically-relevant databases, which
      is still in an early development stage, is useful in selecting the most
      appropriate database(s) in accordance with special items of interest. Applying
      our five chosen criteria, the databank CA (Chemical Abstracts) turns out to be
      the best, followed by four other databanks, which cannot be compared with each
      other.

PMID- 7624881
TI  - Effect of treatment with mercury chloride and lead acetate during the second
      stage of rapid postnatal brain growth on delta-aminolevulinic acid dehydratase
      (ALA-D) activity in brain, liver, kidney and blood of suckling rats.
AB  - The sensitivity of developing rodents to toxic metals differs considerably from
      that of adults. In the present study, we investigated the in vivo and in vitro
      effects of inorganic mercury and lead on delta-aminolevulinic acid dehydratase
      (ALA-D) from brain, liver, kidney and blood of young rats. Eight day-old rats
      were injected with one or five doses of lead acetate (0, 3.5, or 7.0 mg/kg) or
      HgCl2 (0, 2.5, or 5.0 mg/kg). In vitro, the IC50 for mercury inhibition of
      cerebral, renal and hepatic ALA-D was in the 124 to 160 microM range, while
      values for lead acetate was in the 7 to 12 microM range. The IC50 of blood enzyme
      for lead (0.8 microM) and mercury (6.5 microM) was significantly lower than that
      observed for the other tissues. A single dose of lead did not affect the enzyme
      activity, but a single dose of HgCl2 (5 mg/kg) caused a significant inhibition of
      ALA-D from kidney (40%, P < 0.01) and liver (25%, P < 0.05). Five doses of lead
      acetate (3.5 or 7 mg/kg) caused an inhibition of about 25 and 40%, respectively
      (P < 0.01), of hepatic ALA-D, and an increase of 1.4-fold (P < 0.05) and 2.6-fold
      (P < 0.01) of blood enzyme, respectively. Treatment with five doses of HgCl2 (5
      mg/kg) caused an inhibition of about 25, 60, 50, and 80% of ALA-D from brain,
      blood, liver and kidney, respectively (all P < 0.05). Five doses of 2.5 mg/kg
      HgCl2 caused an inhibition of ALA-D from liver (40%, P < 0.01) and kidney (45%, P
      < 0.01). These results demonstrate that ALA-D from young rat tissues show
      different sensitivities to mercury and lead. The enzyme was more affected by
      mercury than by lead in vivo, while in vitro lead was more potent that mercury as
      an ALA-D inhibitor.

PMID- 7624882
TI  - Mode of action of bolesatine, a cytotoxic glycoprotein from Boletus satanas Lenz.
      Mechanistic approaches.
AB  - Bolesatine is a potent cytotoxic glycoprotein purified from Boletus satanas Lenz,
      which has previously been shown to be an inhibitor of protein synthesis in
      several in vitro systems and in vivo. For a better understanding of its mechanism
      of action on protein synthesis at the ribosomal level, rat liver ribosomes were
      pretreated with bolesatine (1 to 10 micrograms) added to in vitro polyuridylic
      acid (poly(U)) translation systems before and after washing. The fact that
      ribosomes were still active confirmed that bolesatine cannot be included in the
      group of protein synthesis inhibitors of plant origin, known as ribosome
      inactivating proteins (RIPs). The effect of bolesatine on the EF-2 elongation
      factor and post-ribosomal fraction was then studied in vitro. The results
      indicated that bolesatine does not have a direct effect on elongation factors,
      but hydrolyses the nucleoside triphosphates, GTP (80% to 90%, respectively for 1
      to 10 micrograms) and ATP (10% to 40%, respectively for 1 to 10 micrograms), with
      consequent inhibition of protein synthesis. Thus, bolesatine should be classified
      as a nucleoside triphosphate phosphatase, rather than as a direct inhibitor of
      protein synthesis. The study of the effect of bolesatine on the EF-2 factor
      revealed that the mechanism whereby bolesatine affects protein synthesis probably
      involves GTP hydrolysis rather than EF-2 inhibition.

PMID- 7624883
TI  - The acute effect of lead acetate on glucocorticoid regulation of tyrosine
      aminotransferase in hepatoma cells.
AB  - Specific cellular sites of action of the environmental pollutant, lead, have not
      been completely defined. The present investigations were conducted to test the
      hypothesis that lead exposure perturbs glucocorticoid-mediated effects in
      hormonal target tissues. The cell culture model chosen for these investigations
      was the effects of lead on glucocorticoid-regulated tyrosine aminotransferase
      (TAT) specific activity in the H4-II-C3 hepatoma cells. Cells were treated with
      300 nM-10 microM lead acetate for 24 or 48 h in absence or presence of the
      inducing agent, dexamethasone. Lead dose-dependently inhibited TAT specific
      activity up to 52% and 61% following 24 and 48 h lead treatments, respectively.
      These treatment times and concentrations of lead acetate did not significantly
      alter total cell numbers, [3H]thymidine incorporation or trypan blue exclusion.
      Glucocorticoid receptor-binding studies yielded a Kd = 8.3 nM and a Bmax = 290
      fmol/mg protein in untreated cells versus a Kd = 9.2 nM and Bmax = 262 fmol/mg
      protein in cells exposed to 10 microM lead acetate for 48 h. Treatment with lead
      did not significantly perturb uptake of the inducing glucocorticoids or initial
      cytosolic receptor-binding events. To sustain induced levels of TAT,
      glucocorticoid must be continuously present. Following steroid withdrawal, enzyme
      de-induction was significantly altered in lead-treated cells. At 6 h following
      dexamethasone withdrawal, TAT levels had decreased to 51% of maximum in sodium
      acetate-treated cells. This was significantly reduced to 33% of maximum in lead
      acetate-treated cells. Lead treatment of HTC cells was also shown to ameliorate
      PMA amplification of dexamethasone-induced TAT activity. Taken together, these
      results suggest that acute exposure of cells to lead may inhibit processes
      involved in glucocorticoid-mediated enzyme induction within the hormonal target
      cell. Results suggest that lead may be acting to increase the turnover of TAT by
      actions at the transcription, translation and/or posttranslational level. Lead
      may also be affecting PKC-mediated phosphorylations in the glucocorticoid-TAT
      signal transduction system.

PMID- 7624884
TI  - The toxicity of the mutagen 'MX' and its analogue, mucochloric acid, to rainbow
      trout hepatocytes and gill epithelial cells and to Daphnia magna.
AB  - The cytotoxicity of the, in Salmonella, potent mutagenic compound, 3-chloro-4
      (dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) and its structural analogue 3,4
      dichloro-5-hydroxy-2[5H]-furanone (mucochloric acid, MCA), was studied in freshly
      isolated rainbow trout hepatocytes and gill epithelial cells by determining 86Rb
      leakage and decrease in fluorescence intensity in calcein AM-loaded cells. The
      acute toxicity of the compounds to Daphnia magna was studied by determining the
      concentration causing immobilization of the organism. MX proved to be more toxic
      than MCA both in the cellular assays and in the acute toxicity test with D.
      magna. MX was more toxic to hepatocytes than to gill epithelial cells. The uptake
      of [14C]MX was also much more efficient in hepatocytes than in gill epithelial
      cells. The uptake of [14C]MX in hepatocytes was not inhibited by taurocholic acid
      in excess, indicating that MX is not taken up by the carrier complex responsible
      for the uptake of taurocholate in the hepatocytes. Both the acute toxicity to D.
      magna and cytotoxicity of MX and MCA was rather low (EC50 values > 0.1 mM) and we
      conclude that it is very unlikely that MX and MCA at concentrations occurring in
      recipients receiving chlorination effluents from pulp mills or chlorinated
      domestic sewage, as regards their acute toxicity, implies a risk for aquatic
      animals.

PMID- 7624886
TI  - Cadmium-induced nephrotoxicity in rhesus monkeys (Macaca mulatta) in relation to
      protein calorie malnutrition.
AB  - In this study, we compared results obtained in protein calorie malnourished (PCM)
      monkeys and controls given Cd2+ (5 mg Cd2+/kg body wt./day) orally for 24 weeks.
      After 16 weeks of Cd2+ exposure, an indolent renal failure develops in PCM
      monkeys which resulted in significant increase in urinary excretion of total
      protein, Cd2+, Zn2+ and Ca2+ as compared to corresponding to Cd(2+)-treated
      control group. In isolated proximal tubule brush border membrane vesicles (BBMV),
      Cd2+, Zn2+ and Ca2+ transport were significantly impaired in Cd(2+)-exposed PCM
      monkeys as compared to Cd(2+)-treated controls. The mechanism of higher urinary
      excretion of Cd2+, Zn2+ and Ca2+ was examined by analyzing the kinetic parameters
      of transport systems. The kinetic studies of Cd2+, Zn2+ and Ca2+ transport
      systems in the BBMV preparations of Cd(2+)-exposed PCM monkeys exhibited a
      significant decrease in Vmax and an appreciable increase in Km as compared to
      Cd(2+)-treated controls. These findings suggested that Cd2+ treatment of PCM
      monkeys caused either a decrease in the number of transporters in the brush
      border membrane or an increase in the number of less active transporters for
      Cd2+, Zn2+ and Ca2+. Furthermore, brush border membrane-bound enzymes, viz.
      alkaline phosphatase and leucine aminopeptidase, activities were significantly
      impaired in Cd(2+)-exposed PCM monkeys. Cadmium content in kidney cortex of
      Cd(2+)-exposed PCM monkeys was 3.34-fold higher than Cd(2+)-exposed controls.
      These findings also established that Cd2+ not bound to metallothionein (MT) was
      significantly higher in Cd-exposed PCM monkeys, which may be an important
      determinant in renal toxicity by interacting with sensitive sites in the renal
      cells and causing renal damage in Cd-exposed PCM monkeys.

PMID- 7624885
TI  - Effect of dimethyl sulfoxide on N-(3,5-dichlorophenyl)succinimide (NDPS) and NDPS
      metabolite nephrotoxicity.
AB  - Dimethyl sulfoxide (DMSO) is frequently used as a solvent to assist in dissolving
      compounds which are not readily soluble in other injection vehicles. The purpose
      of this study was to determine the suitability of DMSO as a vehicle for
      administering the nephrotoxicant, N-(3,5-dichlorophenyl)succinimide, (NDPS) and
      two nephrotoxicant NDPS metabolites, N-(3,5-dichlorophenyl)-2-hydroxysuccinimide
      (NDHS) and N-(3,5-dichlorophenyl)-2-hydroxysuccinamic acid (NDHSA). Male Fischer
      344 rats (4/group) were administered a single intraperitoneal injection of NDPS
      (0.4 or 0.8 mmol/kg), NDHS (0.1 or 0.2 mmol/kg), or NDHSA (0.1 or 0.2 mmol/kg)
      dissolved in 25% DMSO in sesame oil or 100% sesame oil (2.5 ml/kg), while control
      rats received vehicle only. Renal function was then monitored at 24 and 48 h.
      Including DMSO in the vehicle markedly attenuated NDPS 0.4 mmol/kg-induced
      nephrotoxicity and reduced NDPS 0.8 mmol/kg-induced renal effects. Thus, the
      magnitude of the attenuating effect of DMSO depended in part on the
      nephrotoxicant dose of NDPS. In addition, NDHS nephrotoxicity was not altered by
      DMSO and only slight effects on NDHSA nephrotoxicity were observed. These results
      suggest that DMSO is capable of attenuating NDPS nephrotoxicity, and that the
      primary mechanism of this interaction might be due to an inhibition of the
      biotransformation of NDPS to NDHS.

PMID- 7624887
TI  - Genotoxicity of sediment extracts obtained in the vicinity of a creosote-treated
      wharf to rainbow trout hepatocytes.
AB  - Genotoxicity and cytotoxicity were evaluated in rainbow trout hepatocytes exposed
      to sediment extracts obtained in the vicinity of a creosote-treated wharf.
      Sediment cores were collected at the intertidal and subtidal sections of the
      wharf at distances of 1, 5, 40 and 50 m. Moreover, subsamples were also taken at
      different depths of the cores ranging from 2 to 10 cm below the sediment/water
      interface. Sediment samples were air-dried and extracted in dichloromethane
      followed with an exchange into dimethylsulfoxide (DMSO). Rainbow trout
      hepatocytes were exposed for 24 h at 15 degrees C to several concentrations of
      the sediment extract. Afterwards, the cells were collected, and cell viability
      was assayed along with genotoxicity using the nick translation and the alkaline
      precipitation assays. Results showed that the wharf contained high concentration
      of polycyclic aromatic hydrocarbons (PAHs), displayed genotoxicity and
      cytotoxicity to hepatocytes. In addition, PAHs, cytotoxicity and sometimes
      genotoxicity were detected in all sediment samples and tended to decrease with
      distance. Chemical contamination and (geno)toxic effects were greater in sediment
      extracts from the intertidal section than from the subtidal section. However, no
      evident change in chemical or toxicological characteristics was noted between
      samples obtained at different depths. Spearman rank-correlation analysis revealed
      some trends between levels of some PAHs and (geno)toxicity in hepatocytes exposed
      to sediment extracts.

PMID- 7624888
TI  - Effects of dithiocarbamates and cadmium on the enzymatic activities in liver,
      kidney and blood of mice.
AB  - The effects of N-benzyl-D-glucamine dithiocarbamate (BGD), diethyldithiocarbamate
      (DDTC), and N-p-hydroxymethylbenzyl-D-glucamine dithiocarbamate (HBGD) on the
      enzymatic activities in mice were studied. The mice were given i.v. injections of
      these chelating agents (1 mmol/kg) and 3 h later the activities of aspartate
      aminotransferase (AST), alanine aminotransferase (ALT), gamma
      glutamyltranspeptidase (gamma-GTP), alkaline phosphatase (ALP), leucine
      aminopeptidase (LAP), and cholinesterase (ChE) in the liver, kidney, and blood
      were determined. These enzymatic activities were little changed by treatment with
      these chelating agents. Cadmium (Cd) administration markedly decreased the
      activities of AST and ALT in the liver and kidney and greatly increased these
      enzymatic activities in blood. The changes in the enzymatic activities by
      treatment with Cd were prevented by injection of BGD (1 mmol/kg). These results
      indicate that BGD, DDTC, and HBGD were not toxic to the liver or kidney of mice
      and that BGD treatment protected against the acute hepatic and renal toxicity
      induced by Cd.

PMID- 7624890
TI  - Mineral fiber-induced leukocyte activation: the role of intra- and extracellular
      calcium.
AB  - The role of intra- and extracellular calcium in the activation of human
      polymorphonuclear leukocytes (PMNL) to produce reactive oxygen metabolites (ROM)
      were studied by using soluble, formyl-methionyl-leucyl-phenylalanine (fMLP) or
      phorbol myristate acetate (PMA), or particulate stimuli, quartz or chrysotile. A
      calcium channel inhibitor, verapamil, attenuated only quartz-induced elevation of
      free intracellular calcium ([Ca2+]i) and ROM production. Likewise, ethyleneglycol
      bis (aminoethyl ether) tetraacetic acid (EGTA) attenuated quartz-, chrysotile-
      and fMLP-induced elevation of [Ca2+]i and ROM production. It also inhibited PMA
      induced ROM production. A calcium ionophore, A23187 amplified ROM production by
      all of these stimuli. These results suggest that both intra- and extra-cellular
      calcium are required for the full activation of respiratory burst by soluble and
      particulate stimuli in human PMNL.

PMID- 7624889
TI  - Thermolabile hemoglobin formation by 2-cyanaziridine derivatives.
AB  - The erythrocyte toxicity of imexone, azimexone, ciamexone, and its derivatives
      was assessed by means of the thermolabile hemoglobin formation test. After
      administration of doses up to 500 mg/kg to mice, imexone had no effect, whereas
      in accordance with previous studies azimexone strongly and ciamexone moderately
      enhanced thermolabile hemoglobin formation. With regard to the derivatives
      (metabolites) of ciamexone, the alcohol was as active as ciamexone itself,
      whereas ciamexone aldehyde gave a weak reaction. Both ciamexone acid and
      ciamexone-cysteine had no influence. Demethyl ciamexone, however, was more toxic
      than ciamexone, further indicating that the metabolic oxidation of the methyl
      group represents a detoxifying step. In contrast to the in vivo results, after
      incubation with blood samples solely imexone (in the range of mg/ml blood) but
      none of the other 2-cyanaziridines enhanced thermolabile globin formation.
      Preincubation of imexone with cysteine inhibited this effect. The results are
      discussed in view of the hypothesis that binding of the nitrile group of the 2
      cyanaziridines to mercapto groups of proteins precedes their biological effects.

PMID- 7624891
TI  - 3,5-Dichloroaniline toxicity in Fischer 344 rats pretreated with inhibitors and
      inducers of cytochrome P450.
AB  - 3,5-Dichloroaniline (3,5-DCA), a derivative needed in the manufacture of dyes,
      pesticides and industrial compounds has been reported to induce renal damage.
      This study investigated whether pretreatment with inducers or inhibitors of P450
      altered 3,5-DCA toxicity. P450 levels were induced in male Fischer 344 rats (4
      12/group) by pretreatment (i.p.) with phenobarbital (PB, 75 mg/kg/day for 3
      days), beta-naphthoflavone (BNF, 100 mg/kg/day for 4 days) or pyridine (PYR, 100
      mg/kg/day for 4 days). P450 activity was inhibited by pretreatment with piperonyl
      butoxide (PiBx) 30 min prior to injection of 3,5-DCA. Upon completion of a
      designated pretreatment regimen, 0.4 or 0.8 mmol/kg 3,5-DCA was injected into
      F344 rats. Pair-fed controls were injected with 25% ethanol solution or
      physiological saline (2.5 ml/kg). The renal changes monitored at 24 and 48 h
      following treatment with 0.8 mmol/kg 3,5-DCA were characterized by increased
      blood urea nitrogen (BUN) level and decreased renal cortical slice accumulation
      of p-aminohippurate (PAH). Plasma alanine transaminase activity (ALT/GPT) was
      increased 24 h after injection of 0.8 mmol/kg 3,5-DCA while liver wt. was
      unchanged. PB or PYR pretreatment did not alter the renal or hepatic effects of
      3,5-DCA while BNF pretreatment slightly reduced toxicity. In contrast, PiBx
      pretreatment increased the renal and hepatic changes associated with 3,5-DCA. The
      results with PiBx suggest that either the parent compound possesses some direct
      cytotoxicity or that a toxic metabolite was generated through a biotransformation
      pathway not inhibited by PiBx.

PMID- 7624892
TI  - Enhancement of tissue lipoperoxidation in propanil-treated rats.
AB  - The i.p. injection of the herbicide propanil to male Sprague-Dawley rats
      increased the susceptibility to lipoperoxidation of liver and brain rat
      microsomes. A liver damage produced by propanil treatment was demonstrated by
      decreased serum levels of cholesterol and triglycerides as compared to serum
      levels of the lipids in control rats. The cellular damage of rat liver was also
      confirmed by the increased serum levels of aspartate aminotransferase and
      alkaline phosphatase activities observed in propanil-treated rats as compared to
      their activities in control rats.

PMID- 7624893
TI  - Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on estrous cyclicity and
      ovulation in female Sprague-Dawley rats.
AB  - The effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on estrous cyclicity and
      ovulation in Sprague-Dawley rats was examined. TCDD at a single oral dose of 10
      micrograms/kg resulted in irregularity of cycles, characterized mainly as
      prolonged periods of diestrus. In rats cycling normally this dose of TCDD reduced
      the ovulatory rate and the number of ova recovered. The results suggest that TCDD
      is a reproductive toxin also in female rats, the mechanism of which is as yet
      unknown.

PMID- 7624894
TI  - Effect of dietary restriction on glutathione S-transferase activity specific
      toward aflatoxin B1-8,9-epoxide.
AB  - Dietary restriction (DR) reduced the metabolic activation of aflatoxin B1 (AFB1)
      in rats. This reduction may be attributed to the decrease of cytochrome P-450
      mediated AFB1 epoxidation and/or increase in the detoxification of AFB1 catalyzed
      by hepatic glutathione S-transferase (GST) and other phase II detoxification
      enzymes. In this study the effect of DR on male rat liver cytosolic GST activity
      toward AFB1-8,9-epoxide was studied. The chemically-synthesized AFB1-8,9-epoxide
      was used as the substrate in this assay, and the formation of AFB1-GSH conjugate
      was analyzed by HPLC. Male Fischer 344 rats fed DR diets (60% of the food
      consumption of ad libitum (AL)-fed rats) showed a 2.4-fold increase in GST
      activity when AFB1-epoxide was used as the substrate. The results from the enzyme
      kinetic study showed that DR increased Vmax of the liver cytosolic GST but not
      the Km. Acute DR has little or no impact on GST activity when 1-chloro-2,4
      dinitrobenzene and 2,4-dichloronitrobenzene were used as substrates. The mouse
      liver GST activity toward AFB1-epoxide was 3-fold greater than that of
      phenobarbital-induced rats, 4.5-fold greater than DR rats, and 14.7-fold greater
      than the GST activity of AL rats. This direct assay of liver GST activity using
      AFB1-epoxide as the substrate is useful for studying AFB1-induced biomarkers,
      such as AFB1-GSH conjugation and AFB1-DNA adducts.

PMID- 7624895
TI  - Effects of gestational and lactational exposure to coplanar polychlorinated
      biphenyl (PCB) congeners or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on thyroid
      hormone concentrations in weanling rats.
AB  - Perinatal exposure to polychlorinated biphenyl (PCB) mixtures or to certain ortho
      substituted PCB congeners dramatically reduces circulating thyroxine (T4)
      concentrations. It is not clear whether perinatal exposure to coplanar PCBs or
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has a similar effect. In this study,
      time-mated Sprague-Dawley rats were dosed with 2 or 8 mg/kg/day PCB 77 (3,3',4,4'
      tetrachlorobiphenyl), 0.25 or 1.00 micrograms/kg/day PCB 126 (3,3',4,4',5
      pentachlorobiphenyl), 0.025 or 0.10 microgram/kg/day TCDD, or corn oil vehicle
      orally on gestation days 10-16. At weaning, plasma total T4 concentrations in PCB
      77 and TCDD high-dose female pups were significantly depressed, but the changes
      were modest (84.4 and 79.6% of control, respectively). T4 concentrations in PCB
      126 high-dose females and all high-dose males were also depressed slightly, but
      the changes were not statistically significant. UDP-Glucuronosyl transferase (UDP
      GT) activity towards 4-nitrophenol was increased in all high-dose groups. Thus,
      the modest decreases in T4 could be due in part to increased T4 glucuronidation
      by UDP-GT. Triiodothyronine (T3) and thyroid stimulating hormone (TSH)
      concentrations were unchanged in all groups. In contrast to the minor changes in
      thyroid hormone status, liver microsomal ethoxyresorufin-O-deethylase (EROD) was
      markedly induced in all exposure groups and thymus weights were depressed in the
      high-dose groups. Because doses of coplanar PCBs or TCDD that caused marked
      induction of EROD activity had only minor effects on T4, we conclude that changes
      in thyroid hormone status at weaning are not among the more sensitive effects of
      perinatal exposure to these compounds.

PMID- 7624896
TI  - Changes in the serum protein binding of vancomycin in patients with methicillin
      resistant Staphylococcus aureus infection: the role of serum alpha 1-acid
      glycoprotein levels.
AB  - The relationship between albumin or alpha 1-acid glycoprotein (AAG) levels and
      vancomycin (VCM) protein binding was studied in 44 serum samples from the 10
      patients with methicillin-resistant Staphylococcus aureus (MRSA) infection
      receiving VCM therapy. Eighty serum samples from 80 healthy subjects were used as
      a control for albumin and AAG levels. The protein binding percentage of VCM in
      the serum of the patients varied widely from 27 to 62%. The mean albumin level
      (34 g/L) was significantly lower than that in healthy subjects (46 g/L). There
      was no correlation between the binding percentage and serum albumin level in the
      patients (r = -0.25, p > 0.1). The mean AAG level in the patients (1.51 g/L) was
      significantly higher than in healthy subjects (0.59 g/L). There was a significant
      correlation between the binding percentage of VCM and serum AAG level (r = 0.63,
      p < 0.001). The binding percentage of VCM individual patients changed in parallel
      to serum AAG and C-reactive protein (CRP) levels, which is a useful marker of
      acute phase response. There were also significant correlations between AAG,
      albumin, and CRP levels. The present results indicate that the increased AAG
      level in serum of the patients appeared to have a significant effect on the
      protein-binding characteristics of VCM.

PMID- 7624897
TI  - Stability of debrisoquine (CYP2D6) phenotype in liver transplant patients.
AB  - Liver metabolism may be modified after liver transplantation according to the
      phenotype of the donor and may be influenced by posttransplantation
      complications. The CYP2D6 phenotype was assessed in 13 patients (group I) before
      and after liver transplantation using debrisoquine. CYP2D6 activity was also
      assessed in vitro on microsomes from the liver of the recipients and the donors,
      using dextromethorphan. Twelve patients were extensive metabolizers both before
      and after transplantation. One apparently poor metabolizer was transplanted with
      the liver of another poor metabolizer. The intrinsic clearance of
      dextromethorphan (CL(int)) measured on recipient liver microsomes was
      significantly lower than that on donor liver microsomes (p < 0.05). In extensive
      metabolizers, the debrisoquine metabolic ratio was correlated with CL(int) before
      (r = 0.78, p < 0.05) and after (r = 0.89, p < 0.0005) transplantation.
      Debrisoquine phenotype was measured repeatedly in nine additional patients (group
      II) up to 3 years after liver transplantation. Their phenotype was stable during
      the follow-up observation, although the variations observed may be clinically
      relevant. Therefore, no change in CYP2D6 phenotype (extensive/poor metabolizer)
      was observed because of the liver transplantation, and the debrisoquine log
      metabolic ratio was largely unaffected by the liver complications observed during
      the posttransplantation follow-up observation.

PMID- 7624898
TI  - Dextromethorphan polymorphic hepatic oxidation (CYP2D6) in healthy black American
      adult subjects.
AB  - The objective of this study was to assign metabolizer phenotype to 107 healthy
      adult black Americans using dextromethorphan as the substrate probe. Eligible
      subjects were unrelated, healthy, nonsmoking, aged 18-50 years, and taking no
      medications. Fifteen milliliters of dextromethorphan syrup (85 mumol, 30 mg) was
      administered orally at bedtime, and 8-h overnight urine was collected.
      Dextromethorphan and dextrorphan urinary areas and molar ratios were determined
      using high-performance liquid chromatography with fluorescence detection. A molar
      metabolic ratio of < 0.3 was used to segregate poor metabolizers (PM) from
      extensive metabolizers (EM). Data were obtained in 99 subjects: 68 women, 31 men.
      (Five were lost to follow-up, three did not take the probe drug.) Six (6.1%) were
      PM (five women, one man), and 93 were EM. The prevalence of PM was 6.1% (95%
      confidence interval, 2.3-12.7%) in our sample. This compares to 5 to 10% reported
      in white unrelated subjects and 1.9% in 106 black children (64 healthy and 42
      with cancer), and 0-8.6% in black African populations. The clinical implications
      of these findings warrant further investigation.

PMID- 7624899
TI  - Monoethylglycinexylidide as an early predictor of posttraumatic multiple organ
      failure.
AB  - The prognostic value of a dynamic liver-function test, based on the hepatic
      conversion of lidocaine to monoethylglycinexylidide (MEGX), in predicting
      multiple organ failure (MOF) was prospectively investigated in 28 critically ill
      patients after multiple trauma. The MEGX test and conventional static liver tests
      (bilirubin, aspartate aminotransferase, glutamate dehydrogenase, and factor V)
      were performed on days 1, 3, 5, and 7 after trauma. Patients were classified by a
      modified MOF score into a group without (n = 18) and a group with the MOF
      syndrome (n = 10). One patient who developed MOF on the basis of a bacterial
      septicemia was excluded from the general evaluation. No significant differences
      were observed in the MEGX values of the two groups on day 1. All patients who
      subsequently developed MOF, however, displayed a sharp decrease in their MEGX
      values between days 1 and 3. Analysis of the data using receiver operating
      characteristic (ROC) curves revealed that the results of the MEGX test on day 3
      provided the greatest discriminating power between patients with and without
      subsequent MOF. A cut-off MEGX value of 30 micrograms/L on day 3 was associated
      with a prognostic sensitivity of 89% and a prognostic specificity of 94%.

PMID- 7624900
TI  - Multicenter quality control study of amikacin assay for monitoring once-daily
      dosing regimens. International Antimicrobial Therapy Cooperative Group of the
      European Organization for Research and Treatment of Cancer.
AB  - During once-daily dosing regimens of aminoglycosides, administration of large
      single doses results in high peak levels and low 24-h trough levels. However,
      commercial assays for monitoring aminoglycoside levels are designed to cover the
      smaller range of serum concentrations usually observed during multiple daily
      dosing regimens. The study assessed (a) the range of serum concentrations during
      once-daily dosing of amikacin and (b) the performance of a widely used assay
      system for measuring concentrations within this range. A total of 42 dosing
      intervals from eight patients receiving a once-daily regimen of amikacin (20
      mg/kg) were monitored. Median (and range) of peak, 8- and 24-h trough levels were
      61 (25-89), 5.9 (2.2-19), and 1.3 (< 0.8-6.2) mg/L, respectively. The accuracy of
      a fluorescence polarization immunoassay for measuring concentrations of amikacin
      during once-daily dosing regimens was assessed in an international multicenter
      study. The performance of the assay was excellent for peak and 8-h
      concentrations; median deviations from the target concentrations were < 5%. The
      majority of the trough levels (26 of 42) measured in patients during once-daily
      treatment were within the range of 1-2 mg/L and could also be determined with an
      accuracy sufficient for clinical monitoring (median deviations 14%).

PMID- 7624901
TI  - Can low-dose clozapine pharmacokinetics predict steady-state plasma
      concentration?
AB  - Plasma concentrations of clozapine at a given dose vary considerably between
      patients, but drug levels are not routinely monitored during the normal 4- to 8
      week dose escalation period at the beginning of therapy. We hypothesized that the
      dose required to give a putative threshold therapeutic concentration of 350
      micrograms/L could be individualized using pharmacokinetic predictions made at
      the beginning of normal dose escalation. Low-dose clozapine (25-75 mg every 12 h)
      was administered to 21 treatment-resistant patients with schizophrenia who had
      been split into three groups. In group A (six patients), individual target doses
      were predicted from area under the concentration-time curve data after a single
      50-mg dose. In group B (five patients), predictions were made as in group A but
      at steady state. In group C (10 patients), predictions were based on trough
      clozapine levels obtained at steady state immediately before dose increase.
      Dosage was increased, if tolerated, by 25 mg twice daily three times a week for 4
      8 weeks according to established clinical practice. Clozapine concentrations were
      measured weekly, and actual target doses were determined for each patient from
      dose-concentration plots. In groups A and B, the correlation between actual and
      predicted target dose was not significant (r = 0.18, p = 0.59). In group C,
      however, it was significant (r = 0.86, p = 0.0016). These results suggest that
      individualized doses of clozapine for treatment-resistant patients with
      schizophrenia can be conveniently predicted from trough drug levels at the start
      of therapy. Such information would facilitate a more rapid, individualized, and
      consistent attainment of therapeutic doses than is now the case in clinical
      practice.

PMID- 7624902
TI  - Effect of diuretic drugs on creatinine clearance determination.
AB  - Diuretic drugs have been reported to alter the glomerular filtration rate and
      possibly the creatinine excretion by the kidneys. We evaluated the effects of
      single doses of diuretic drugs on creatinine clearance determination. Ten healthy
      volunteers were randomized to receive either oral hydrochlorothiazide, oral
      furosemide, intravenous furosemide, or no treatment in a cross-over fashion
      during four separate test days with 6-day washout periods. Urine and blood
      specimens were collected during 24 h after the treatments. Specimens were assayed
      for creatinine, and the creatinine clearance corresponding to the 4-, 6-, 12-,
      and 24-h urine collections were calculated. Analysis of variance did not show a
      statistically significant effect of the diuretic regimens on creatinine clearance
      over these periods. This study demonstrates that single doses of diuretic drugs
      do not have significant effect on creatinine clearance determination using urine
      collected during 4-24-h periods.

PMID- 7624903
TI  - Nomogram for estimating plasma unbound disopyramide concentrations in patients
      with varying plasma alpha 1-acid glycoprotein concentrations.
AB  - Since plasma protein binding of disopyramide (DP)--a class IA antiarrhythmic
      widely used in the prevention and treatment of various types of cardiac
      arrhythmias--is not only saturable within the therapeutic range but also altered
      under various pathophysiological conditions, the interpretation of total DP
      concentrations, Ctotal, measured during routine therapeutic drug monitoring (TDM)
      is often complicated. To circumvent this problem, we attempted to establish a
      comprehensive nomogram that allows estimation of unbound DP concentrations (Cu)
      based upon Ctotal of the drug and plasma concentration of alpha 1-acid
      glycoprotein (AAG), a major DP-binding protein. The nomogram was formulated with
      use of the in vitro binding data retrieved from 103 subjects categorized into 10
      different groups each with a different mean concentration of AAG (range: 0.14
      1.54 g/L). Data analysis, using a binding model assuming one specific binding
      site and nonspecific binding(s), revealed that alterations in plasma DP binding
      are attributable mainly to those in the capacity, Bmax, rather than affinity, ka,
      constant of the specific binding site. In addition, plasma AAG concentration
      correlated significantly (r = 0.90, p < 0.001) with the Bmax value over the range
      0.09-2.28 g/L. For this reason, we substituted Bmax calculated by the regression
      equation as a function of AAG and the overall mean ka and nonspecific binding
      parameter values for the respective individual variables of the binding model, so
      that Cu of each plasma sample was estimated from the corresponding data on Ctotal
      and plasma AAG levels.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7624904
TI  - Liquid chromatographic analysis of mesna and dimesna in plasma and urine of
      patients treated with mesna.
AB  - We describe in this report an expedient and accurate liquid chromatographic
      method for measurement of mesna and dimesna in plasma and urine. The separation
      of mesna and the internal standard (p-aminobenzoic acid, IS) was achieved on a 10
      microns, 8 mm (i.d.) x 10-cm C18-Resolve cartridge in conjunction with radial
      compression system. An aqueous solution of sodium citrate (0.1 M), tetrabutyl
      ammonium phosphate (0.001 M), and triethylamine (1:10,000, vol/vol), adjusted to
      pH 5 with 85% phosphoric acid was used at a flow rate of 2 ml/min as a mobile
      phase. The compounds were detected in the effluent electrochemically at +450 mV.
      After an appropriate amount of IS was added, the plasma sample (100 microliters
      or fraction thereof) was deproteinized with an equal volume of 0.0825 M sulfuric
      acid containing sodium hexametaphosphate (1.25% wt/vol), whereas urine was
      diluted 1:50 with water and mixed 1:1 with an aqueous solution of sodium
      hexametaphosphate (1.25% wt/vol). Dimesna was reduced back to mesna with sodium
      borohydride before analysis of the total mesna. The peak height ratio (drug/IS)
      varied linearly with the concentration, and the correlation coefficient was >
      0.992 for both mesna and dimesna. The intrarun precision at different
      concentrations of mesna was equally good and the coefficient of variation was
      consistently < 4.5%. No interference from endogenous substances or any
      concomitantly used drug was observed. This assay is currently being used for
      measurement of mesna and dimesna in plasma of bone marrow recipients who receive
      high doses of cyclophosphamide.

PMID- 7624905
TI  - Isothermal gas chromatographic method for the rapid determination of felbamate
      concentration in human serum.
AB  - A rapid isothermal method has been developed for felbamate quantitation in human
      serum. Felbamate and internal standard (2-methyl-2-phenyl-1,3
      propanedioldicarbamate) are isolated from alkalinized serum into methylene
      chloride with a single 90-s extraction. A further concentration step is
      unnecessary. Three microliters of the sodium sulfate-dried extract is injected
      into a GC equipped with a 30 m x 0.25 mm DB-1 column with a 0.25 microns film
      operated in split mode. Detection is by flame ionization. Thermal degradation of
      the carbamates has been minimized and is reproducible. Multiple-analyst day-to
      day coefficient of variation = 3.25% (n = 130) at a felbamate concentration of 25
      mg/L and 2.18% (n = 129) at 100 mg/L. The method is linear to 250 mg/L and the
      lowest concentration to be consistently integrated by the data system was 2.0
      mg/L. No significant interferences were found from 60 commonly encountered drugs.
      Serum felbamate concentrations ranged from 3 to 137 mg/L (n = 212, mean = 56
      mg/L) when assayed by this method, which is suitable for therapeutic drug
      monitoring, pharmacokinetic studies, and overdose monitoring.

PMID- 7624906
TI  - Lamotrigine analysis in serum by high-performance liquid chromatography.
AB  - Lamotrigine is an anticonvulsant drug soon to be introduced to the North American
      market. It is chemically unrelated to any currently available antiepileptic drug.
      The objective of this study was to develop a quantitative high-performance liquid
      chromatography assay for lamotrigine in serum. Lamotrigine was extracted from
      serum at alkaline pH into ethyl acetate after addition of the internal standard
      (BW725C78). After mixing, the organic layer was evaporated to dryness before
      dissolving the residue in methanol for isocratic separation on a RP-8 column (5
      microns) with a mobile phase of water/0.5 M phosphate buffer at pH
      6.5/acetonitrile (790/10/200) with eluant monitoring at 306 nm. Calibration was
      performed with five serum standards (2-32 microM and recovery averaged 88% at 25
      microM. Between-run precision was 4.1 and 2.5% C.V. at 13.6 and 31.6 microM,
      respectively. At room temperature, lamotrigine was stable for a minimum of 7
      days. Interference studies were performed on serum specimens containing commonly
      monitored drugs. The only potentially interfering drug was carbamazepine, which
      elutes 2.5 times longer than lamotrigine. We conclude that this is a reliable
      method for quantitation of lamotrigine in serum.

PMID- 7624907
TI  - Quantitative determination of the antibiotic azithromycin in human serum by high
      performance liquid chromatography (HPLC)-atmospheric pressure chemical ionization
      mass spectrometry: correlation with a standard HPLC-electrochemical method.
AB  - A specific assay for the quantitative determination of the new antibiotic
      azithromycin in a low volume of human serum is described. The assay uses on-line
      high-performance liquid chromatography (HPLC) and atmospheric pressure chemical
      ionization mass spectrometry (HPLC-APCI). Deuterium-labeled azithromycin was
      synthesized and used as the internal standard of the assay. The drug and the
      internal standard are extracted from 50 microliters of serum, and aliquots are
      injected onto a standard reverse-phase HPLC column. The effluent from the HPLC
      column at 1 ml/min is introduced into the atmospheric pressure source of a SCIEX
      API III mass spectrometer. Azithromycin concentrations in serum are determined by
      the selected monitoring of the protonated molecular ions of the drug and the
      internal standard. Our assay yields accurate and precise results over the range
      10 ng/ml to 250 ng/ml. The correlation between the assay and a standard HPLC
      electrochemical method, requiring a larger volume of serum, has been determined.
      The two methods showed excellent agreement. Because of its low volume
      requirement, our HPLC-APCI assay can be substituted for the standard assay for
      the investigation of azithromycin pharmacokinetics in children.

PMID- 7624908
TI  - A new digoxin immunoassay substantially free of interference by digoxin
      immunoreactive factor.
AB  - We have evaluated the new Roche digoxin "On Line" procedure for use in a
      pediatric population with particular interest in the potential for interference
      by digoxin-like immunoreactive factor (DLIF). An initial study comparing digoxin
      values obtained with the new Roche procedure with determinations on an Abbott
      TDx, American Dade Stratus, and COBAS-FARA using Microgenics Cedia reagents,
      found good correlations with these established methods. The Roche method was
      suitably precise and utilized either serum or plasma. Interference by DLIF was
      assessed by analyzing specimens from patients not receiving digoxin but likely to
      contain DLIF, with the argument that non-zero values represent cross-reactivity
      of anti-digoxin antibodies with DLIF endogenous to these specimens. When
      specimens from neonates, women with second/third trimester pregnancies, and
      patients with renal and liver failure were assayed with the Roche, Stratus, and
      TDx methods, all three methods measured DLIF in some specimens, but the Roche
      method possessed the lowest overall DLIF interference. The modest extent of DLIF
      interference and the requirement of a small amount of specimen make the Roche
      method superior in monitoring digoxin in a pediatric population.

PMID- 7624909
TI  - The clinical laboratory in pharmaceutical development.
AB  - The clinical laboratory plays an important part in the development of new
      pharmaceutical agents. The nature of this role will vary depending on the stage
      of clinical development of the drug and the goals of a particular investigation.
      Therefore, it may be appropriate to conduct and interpret clinical trial
      laboratory tests differently from the standard methods used in routine clinical
      analysis. The training and background of laboratory directors are important in
      providing both prospective and on-site management of laboratory testing during
      pharmaceutical clinical trials.

PMID- 7624910
TI  - Time course of appearance of cotinine in human beard hair after a single dose of
      nicotine.
AB  - The time course of appearance of cotinine in saliva and in daily collections of
      beard clippings was monitored by gas chromatography with mass spectrometry in six
      volunteers who were nonsmokers following a single 30-min buccal administration of
      nicotine as a chewing gum. Salivary cotinine concentrations reached a plateau
      after 1.5 h and were nondetectable (< 0.3 ng/ml) 24 h after drug administration.
      Cotinine was detected in extracts of sodium hydroxide digests of beard hair in
      all subjects on the third day after drug administration. Mean concentrations in
      beard peaked on day 5, and cotinine was not detected (< 0.03 ng/mg) after day 7.
      The data indicate the main route for cotinine incorporation into beard is during
      hair growth. Transfer into beard from sweat is of little importance. A role for
      transfer via sebum is equivocal.

PMID- 7624911
TI  - Carbamazepine-salicylate interaction in normal and uremic sera: reduced
      interaction in uremic sera.
AB  - Displacement of phenytoin and valproic acid by salicylate have been described. We
      studied carbamazepine-salicylate interactions in normal and uremic sera, which
      have not been studied. Salicylate caused significant displacement of
      carbamazepine from protein binding, leading to higher concentrations of free
      carbamazepine. The concentrations of free carbamazepine were always significantly
      higher in uremic sera than in normal sera. However, when uremic sera were
      supplemented with both carbamazepine and salicylate, we observed a much lower
      displacement of carbamazepine and only a slight increase in free carbamazepine
      concentration. Treatment of uremic sera with activated charcoal corrected the
      binding deficiency for carbamazepine. Known uremic compounds like hippuric acid
      and indoxyl sulphate can only partly explain the observed displacement of
      carbamazepine in uremic sera. We conclude that salicylate displaces carbamazepine
      from protein binding in normal sera, but this interaction is significantly
      reduced in uremic sera.

PMID- 7624912
TI  - Plasma platinum elimination in a hemodialysis patient treated with cisplatin.
AB  - The pharmacokinetics of intravenously administrated cisplatin (CDDP) were studied
      in a patient with meduloblastoma receiving regular hemodialysis for chronic renal
      failure. The patient received four CDDP infusions of 25 mg/m2 in two courses and
      underwent hemodialysis before each treatment and in intervals of 48 h thereafter
      with blood sampling at the beginning and the end of each hemodialysis. The data
      obtained were compared with the pharmacokinetic data from follow-up studies of 19
      CDDP treatments in 15 patients suffering from various malignancies with no renal
      failure where a biexponential pharmacokinetic curve was recorded. The data of
      platinum (Pt) elimination of the patient receiving hemodialysis resembled the
      curve of those who had not, but following the second CDDP treatment in each
      course the peak Pt level in plasma was doubled, with a somewhat slower rate of
      elimination.

PMID- 7624913
TI  - The monoethylglycinexylidide test is more useful for evaluating liver function
      than indocyanine green test: case of a patient with remarkably decreased
      indocyanine green half-life.
AB  - Lidocaine was used for evaluation of hepatic function in a patient undergoing
      hepatic resection. Preoperatively, half-life of indocyanine green (ICG) was 33
      min after intravenous administration. Plasma concentration of the N-dealkylated
      metabolite of lidocaine, monoethylglycinexylidide (MEGX), was quantitatively
      determined to evaluate hepatic function. The patient's rate of formation of MEGX
      at 15 min after administration of lidocaine was within normal limits, at 56
      micrograms/L. These findings suggest that in this patient, hepatic cytochrome P
      450IIIA activity was not impaired, but selective impairment of uptake of ICG into
      hepatocytes or excretion into the bile ducts was present. The rate of formation
      of MEGX was decreased, and plasma concentration of bilirubin was elevated
      postsurgically; this could have been the result of decreased cytochrome P-450IIIA
      activity or decreased hepatic blood flow after hepatic resection. We conclude
      that the rate of formation of MEGX is a better index of hepatic function than is
      ICG half-life.

PMID- 7624914
TI  - Gas chromatographic ethylene glycol method: evaluation for diol interference.

PMID- 7624916
TI  - Valproic acid-carbamazepine interaction: is valproic acid a selective inhibitor
      of epoxide hydrolase?
AB  - Steady state plasma carbamazepine (CBZ), carbamazepine epoxide (CBZE), and
      carbamazepine diol (CBZD) concentrations were quantified by HPLC in 121 specimens
      obtained from two groups of epileptic patients: 78 receiving CBZ monotherapy (I),
      and 43 receiving CBZ and valproic acid (VPA) (II). The differences of
      drug/metabolite ratios and concentration/dose (mumol/L/mg/kg/day or 1/clearance)
      ratios were calculated as a measure for the influence of VPA on CBZ metabolism.
      Results as means +/- SD were CBZ/CBZE 5.85 +/- 3.91 (I) vs. 4.22 +/- 1.57 (II), p
      < 0.02; CBZ/CBZD 2.94 +/- 1.94 (I) vs. 2.82 +/- 1.15 (II); CBZE/CBZD 0.53 +/-
      0.24 (I) vs. 0.71 +/- 0.32 (II), p < 0.001. Concentration/dose ratios: CBZ 2.32
      +/- 1.58 (I) vs. 3.04 +/- 1.41 (II), p < 0.05; CBZE 0.41 +/- 0.20 (I) vs. 0.73 +/
      0.28 (II), p < 0.001; CBZD 0.82 +/- 0.35 (I) vs. 1.22 +/- 0.70 (II), p < 0.001.
      Drug/metabolite relationship data seem to support the concept for VPA as a
      selective inhibitor of epoxide hydrolase, but concentration/dose ratios indicate
      a reduced clearance for the parent drug, and especially for its two metabolites.
      This latter finding is in a controversy with the former concept. In addition, a
      considerable age-dependency of the influence of VPA on CBZ metabolism was found:
      compared to monotherapy, drug/metabolite and concentration/dose ratios were most
      changed in children. We assume that VPA is probably not a selective inhibitor of
      epoxide hydrolase, and affects nonspecifically all steps of the epoxide-diol
      pathway of CBZ metabolism.

PMID- 7624915
TI  - Pharmacokinetics of a new oral formulation of cyclosporine in liver transplant
      recipients.
AB  - Trough concentrations of cyclosporine can be highly variable because of its poor
      bioavailability in current oral formulations, Sandimmune (SIM). Neoral (N-SIM) a
      new microemulsion of cyclosporine is more readily absorbed than SIM in healthy
      controls. The present study compared the pharmacokinetic profiles of SIM and N
      SIM following orthotopic liver transplantation. In 16 patients with partial
      biliary diversion, 1 week after transplantation, the bioavailability and peak
      concentration of a single 300 mg dose of N-SIM were greater than SIM by 724% (p =
      0.0019) and 800% (p = 0.0001), respectively. In 39 patients who were on stable
      doses of cyclosporine 1 month after transplantation, the bioavailability of N-SIM
      was higher than that of SIM under both fasting (+64%, p = 0.001) and fed (+37%, p
      = 0.004) conditions. Trough concentrations were similar for the two formulations.
      However, peak concentrations were higher for N-SIM in both fasting (+119%, p =
      0.003) and fed (+53%, p = 0.003) patients. Also, time to peak was shorter for N
      SIM in both fasting (-21%, p = 0.027) and fed (-59%, p = 0.0001) patients. The
      correlation between trough concentrations and bioavailability was greater for N
      SIM than for SIM in fasted (r = 0.80, p = 0.0001 versus r = 0.75, p = 0.0001) and
      fed patients (r = 0.65; p = 0.002 versus r = 0.55; p = 0.012). We conclude that
      the rate of absorption and the bioavailability of N-SIM is significantly and
      consistently better than SIM and may, therefore, improve the therapeutic index of
      cyclosporine after liver transplantation.

PMID- 7624918
TI  - A patient-side technique for real-time measurement of acetylcholinesterase
      activity during monitoring of eptastigmine treatment.
AB  - Rapid and reliable measurement of acetylcholinesterase (AChE) activity is of
      crucial importance to the pharmacodynamic monitoring of anticholinesterase drugs.
      A new assay has been developed to measure AChE from 10 microliter samples of
      capillary blood. AChE activity was calculated from the change in pH of the
      reaction medium caused by the hydrolysis of acetylcholine and measured with a
      highly sensitive differential pH apparatus (CL-10, Eurochem, Rome, Italy).
      Interference by butyrylcholinesterase was eliminated by a specific inhibitor,
      quinidine sulfate. The assay lasts 1 min. The coefficient of variation (CV) for
      replicated measurements was 2.8% (3267 U/L, n = 33). Linearity ranged from 0 to
      10,000 U/L. The correlation coefficient between the new technique and Ellman's
      colorimetric method on washed erythrocytes was r = 0.987 (y = 1.299x - 63, n =
      29). The correlation coefficient between assays on capillary and venous samples
      was r = 0.979 (y = 0.974x + 174, n = 47). A cross-laboratory validation study was
      performed in 10 centers using glycerol-stabilized hemolysates with normal and
      reduced AChE activity. Samples were assayed in triplicate. The within- and
      between-laboratory CVs for samples with normal AChE activity (6,018 U/L) were 2.2
      and 8.1%, respectively. The new method was applied to a double-blind, placebo
      controlled multicenter study of eptastigmine in Alzheimer patients and proved to
      be a simple, noninvasive, rapid, and reliable method for pharmacodynamic
      monitoring of this drug.

PMID- 7624917
TI  - Efficient sampling strategies for forecasting pharmacokinetic parameters of
      irinotecan (CPT-11): implication for area under the concentration-time curve
      monitoring.
AB  - A linear two-compartment Bayesian pharmacokinetic model was developed using a
      standard two-stage population method for the novel anti-cancer agent CPT-11 from
      11 adult patients with refractory cancer. The accuracy and efficiency of this
      Bayesian model for estimating pharmacokinetic parameters including the area under
      the concentration-time curve (AUC) was then evaluated using two different
      sampling strategies in a new study cohort of 13 patients with cancer. Sampling
      strategies included either one, two, or three nonsteady-state feedback levels
      determined empirically and from optimal sampling theory (D-optimality). All 24
      patients in this study received CPT-11 (60 mg/m2) as a 90-min infusion.
      Pharmacokinetic parameters derived from the Bayesian model combined with these
      limited sampling strategies were compared with those parameters obtained from the
      full sample data sets (n = 10) analyzed by weighted nonlinear least squares
      regression (reference method). The least-bias and most precise sampling times for
      estimating AUC were 3.5; 3.5 and 9.5; and 0.5, 3.5, and 9.5 h, respectively. At
      these times, only marginal improvement in precision of the AUC estimate was
      observed using two versus three samples. However, the precision of the estimate
      of clearance was not improved using two versus three samples. The sampling times
      derived from optimal sampling theory were 0.25, 3.5, 8.5, and 24 h and correlated
      closely to the actual and best empirical sampling times of 0.5, 3.5, 9.5, and 24
      h. These results strongly suggest that Bayesian estimation combined with only two
      optimally timed samples accurately predicts the AUC of CPT-11 and should be
      useful for implementing adaptive control dosing for monitoring CPT-11 systemic
      exposure in patients with cancer.

PMID- 7624919
TI  - Bayesian forecasting of serum vancomycin concentrations in neonates and infants.
AB  - A dynamic pharmacokinetic model for i.v. vancomycin administration was developed
      and tested in 47 neonates and infants. Twenty-nine patients (Group 1), having two
      or more concentrations, were used to estimate population parameters by nonlinear
      least-squares analysis. Multiple stepwise linear regression techniques showed
      that estimated creatinine clearance, Clcr, and postnatal age were significant
      demographic factors related to vancomycin clearance (CL). No strong associations
      were found for the apparent volume of distribution. A one-compartment model was
      constructed using the associations of CLcr and postnatal age with vancomycin CL.
      Eighteen patients (Group 2), receiving 35 courses of vancomycin therapy, with
      both initial and subsequent sets of peak and trough concentrations, were used to
      test the predictive performance of the model with and without the use of Bayesian
      forecasting. Using only population-based parameters, the respective mean error
      (ME) (bias) and mean absolute error (MAE) (precision) for predicting subsequent
      peak concentrations were -1.20 and 3.89 mg/L and for trough concentrations, 0.83
      and 2.23 mg/L, respectively. For the Bayesian method, these values were,
      respectively, 0.45 and 4.13 mg/L for peak concentrations and 1.55 and 2.40 mg/L
      for trough concentrations. When predicted concentrations occurred within 30 days
      of feedback concentrations, the Bayesian method tended to be slightly less biased
      and more precise than the population-based parameters. The opposite was true > 30
      days of the initial set of feedback concentrations. The use of population
      specific pharmacokinetic parameters and Bayesian forecasting should allow
      accurate dosage regimen design as well as minimize the need for monitoring serum
      vancomycin concentrations in neonates and young infants.

PMID- 7624920
TI  - Evaluation of therapeutic drug monitoring of methotrexate in saliva of children
      with rheumatic diseases.
AB  - Pediatric patients with leukemia, other malignancies, and rheumatological disease
      receive methotrexate chronically. Because of the documented correlation between
      methotrexate levels of compliance and clinical outcome, it is conceivable to
      verify appropriate systemic exposure to the drug. Saliva sampling may be of
      potential interest, especially in children, in whom blood sampling is ethically
      limited. Our study shows poor correlation between serum total/free methotrexate
      concentrations and saliva levels, precluding the clinical use of this test.

PMID- 7624921
TI  - Optimized method for determination of gabapentin in serum by high-performance
      liquid chromatography.
AB  - The anticonvulsant drug gabapentin and its heptaneacetic acid analog-used here as
      an internal standard--are isolated from serum (pH 9) with an octyldecyl (C-18)
      solid-phase sorbent column. To enhance analytical detection, trinitrobenzene
      derivatives of these extracted compounds are prepared quickly within 10 min. To
      further improve chromatographic selectivity, the derivatives are concentrated on
      a thin C-18 solid-phase membrane and interferences are washed away. The retained
      purified derivatives are eluted from the membrane with a small volume of solvent
      and the eluate is directly injected onto an Ultrasphere C-18 high-performance
      liquid chromatography column with quantification at 340 nm. No evaporation
      concentration steps are necessary. Recoveries (extraction) of gabapentin and the
      internal standard are 94.2 +/- 2.9% and 98 +/- 2.0%, respectively. Analytical
      responses are linear from lower limit of sensitivity of 0.05 mg/L up to at least
      10 mg/L. Between-run coefficients of variation (CV) range from 2.3 to 2.9%
      through the concentration range 0.5-4.0 mg/L. To illustrate the rationale for
      selection of test parameters for a robust method, we present optimization graphs
      for these processes. Moreover, we discuss the advantage of the packed cartridge
      and membrane sorbens as companion extraction devices.

PMID- 7624922
TI  - Determination of droloxifene and two metabolites in serum by high-pressure liquid
      chromatography.
AB  - In this assay of the nonsteroidal antiestrogen droloxifene and two metabolites in
      human serum, the serum samples were deproteinized with an equal volume of
      acetonitrile and then injected into an analytical octadecylsilane column. The
      analytical column was equilibrated with acetonitrile/water (1/1, vol/vol)
      containing acetic acid and diethyl amine and eluted isocratically with 66%
      acetonitrile in the same buffer. Droloxifene, N-desmethyldroloxifene, and 4
      methoxdroloxifene were post-column converted to fluorophors by ultraviolet
      illumination while passing through a 10-m transparent knitted
      polytetrafluorethylene reaction coil. Analytical recovery was close to 100%.
      Within- and between-day precision corresponded to a coefficient of variation (CV)
      of 2-5% at serum concentrations of > or 25 ng/ml, except for 4-methoxydroloxifene
      (CV 7-10% at a concentration of 25 ng/ml). By increasing the injection volume
      from 50 to 250 microliters, the detection limits could be decreased from
      approximately 5 to 1 ng/ml. Conjugated droloxifene could be estimated in a second
      run after treatment of sample with an enzyme preparation containing beta
      glucuronidase plus sulphatase. The recovery of droloxifene glucuronide was close
      to 100%. Sulphate conjugates have not been identified and were not accounted for.

PMID- 7624923
TI  - Rapid serum minocycline assay for pleurodesis monitoring using high-performance
      liquid chromatography with radial compression.
AB  - A high-performance liquid chromatography (HPLC) method has been developed for the
      rapid evaluation of minocycline concentrations in serum after chemical
      pleurodesis. Elution was performed with a Nova-Pak phenyl reverse-phase column
      and a Waters radial compression module. No organic extraction or evaporation of
      samples is required. The assay is linear from 0.6-20 micrograms/ml with recovery
      rates > or = 98%. Interassay variability is 8.2 +/- 1.1% and intraassay
      variability is 2.1 +/- 0.3%. Correlation coefficients were > or = 0.999 for five
      standard curves. The technique was effective for quantitation of serum
      minocycline levels in a human patient who had received the drug intrapleurally on
      two consecutive days. This HPLC method may be useful for monitoring adverse
      effects related to serum concentrations of the drug during pleurodesis.

PMID- 7624924
TI  - Analysis of enantiomers of citalopram and its demethylated metabolites in plasma
      of depressive patients using chiral reverse-phase liquid chromatography.
AB  - A stereospecific high-performance liquid chromatography (HPLC) method has been
      developed for the analysis of the underived enantiomers of citalopram (CIT) and
      its N-demethylated metabolites in plasma. Using fluorescence detection, the limit
      of quantification for each enantiomer is 3 ng/ml. CIT N-oxide and the CIT
      propionic acid derivative are not extracted by the procedure used. Inter- and
      intraday validations of the method using reverse-phase mode HPLC on separate
      acetylated beta-cyclobond columns showed the sensitivity of this assay to be
      suitable for pharmacokinetic studies of the enantiomers of these compounds.
      Plasma levels of the enantiomers and the demethylated metabolites of CIT have
      been determined during routine therapeutic drug monitoring (TDM) in 29 depressive
      patients treated with varying dosages (20-80 mg/day) of CIT. Concentrations of S
      (+)-CIT, which is considered the most potent selective serotonin reuptake
      inhibitors (SSRI) of the CIT and desmethylcitalopram (DCIT) enantiomers, varied
      between 24-49% (mean +/- sd, 35% +/- 5%) of the concentrations of total CIT.
      There were highly significant correlations between S-(+)-CIT and R-(-)-CIT levels
      (r = 0.866; p < 0.0001) and between S-(+)-DCIT and R-(-)-CIT (r = 0.932; p <
      0.0001). The co-medications seemed to have little influence on enantiomer ratios.
      These results suggest the need for studies on the relationships between clinical
      response and plasma levels of CIT enantiomers.

PMID- 7624925
TI  - Analysis of desmethylmethsuximide using high-performance liquid chromatography.
AB  - Analysis of desmethylmethsuximide by high-performance liquid chromatography
      (HPLC) is described. After adding an internal standard (IS), 200 microliters of
      plasma was buffered to pH 4.5 and extracted with dichloroethane. The organic
      solvent was then evaporated to dryness and the residue reconstituted in 100
      microliters of mobile phase prior to injecting a 20 microliters aliquot onto a
      Hypersil 5 MOS column, which was eluted with acetonitrile/acetate buffer (pH 5.5)
      36:64 vol/vol. Constituents were separated in approximately 8 min. Using this
      method, down to 1.0 mg/L of desmethylmethsuximide in plasma can be accurately
      determined. The method is suitable for therapeutic monitoring of
      desmethylmethsuximide in patient samples.

PMID- 7624926
TI  - Plasma concentrations of morphine, morphine-3-glucuronide, and morphine-6
      glucuronide after intravenous and oral administration to healthy volunteers:
      relationship to nonanalgesic actions.
AB  - Healthy volunteers were given morphine as an i.v. infusion (10 mg), immediate
      release (IR) tablets (3 x 10 mg), and as a new controlled release (CR) tablet (30
      mg) on separate occasions. Venous blood samples were analyzed for morphine,
      morphine-3-glucuronide (M3G), and morphine-6-glucuronide (M6G) using high
      performance liquid chromatography (HPLC). Pupil size, salivation, and central
      nervous system (CNS) effects were evaluated serially. Pharmacokinetic parameters,
      calculated using a two-compartment model, were in accordance with previous
      results for i.v. administration of morphine. The absolute bioavailability of
      morphine in both IR and in CR tablets was, 32%, and the relative bioavailability
      of the CR tablet versus the IR tablets was 103% (91-115%, 95% confidence
      interval). Pupil size and unstimulated saliva production were significantly
      reduced and CNS effects most pronounced following i.v. infusion of morphine, but
      were only moderately affected after oral administration with IR or CR tablets.
      Miosis and reduction of salivation were observed at moderate concentrations of
      morphine and M6G. A pharmacokinetic/pharmacodynamic model based on previous
      studies of receptor binding and potency of morphine and its metabolites was used
      to assess the concentration-effect relationships. According to this model, M6G
      was four and eight times more potent than morphine in producing miosis and
      reduction of saliva production, respectively. The same model indicated that
      intrinsic activities of M6G and morphine were similar for both effect parameters,
      whereas M3G was either inactive or even opposed the effects of morphine and M6G.

PMID- 7624928
TI  - Comparison of three methods for cyclosporine area under the curve monitoring
      calculations.
AB  - A method of therapeutic monitoring of cyclosporine by using area under the curve
      (AUC) has been previously proposed. However, different mathematical methods of
      calculating AUC may produce different results. We compared three methods of
      calculating whole blood 12-h AUC of cyclosporine A (CsA) at steady state in 16
      pediatric renal allograft recipients. The linear trapezoidal method tended to
      significantly overestimate AUC when compared with a method combining linear and
      log trapezoidal methods, or the Lagrange technique combined with the logarithmic
      trapezoidal method, producing mean differences of 13.8 ng*h/ml [95% confidence
      interval (CI), 7.3-20.3] and 12.8 ng*h/ml [95% CI, 7.3-18.3], respectively.
      However, these differences appear to be of little clinical significance because
      they comprised < 1% of the calculated AUC value. The calculated AUCs by the three
      methods produced values with similar means and overlapping 95% CI. These data
      suggest that use of any of these three mathematical methods, when used to
      calculate CsA AUC for the determination of average steady-state concentrations
      and dose rate calculations, will produce similar results.

PMID- 7624927
TI  - Oral and intravenous disposition of cyclosporine in psoriatic patients.
AB  - After informed consent was obtained and with the approval of the Local Ethical
      Committee, cyclosporine A (CsA) kinetics was studied in 63 psoriatic patients by
      giving them 2.5 mg/kg CsA orally. In order to calculate oral bioavailability, F,
      22 patients were given the same dose i.v. Values of the calculated kinetic
      parameters were oral F = 22-63%; half-life, t1/2 beta, = 11.05-13.70 h; volume of
      distribution, Vd, = 4.00-5.02/L/kg; total body clearance, Cl, = 4.25-4.14
      ml/min/kg. The area under the blood concentration time curve was more closely
      related to the dose (r = 0.66) than were trough levels (r = 0.52). No significant
      relationship was observed between the kinetic parameters studied and the age of
      the patient.

PMID- 7624929
TI  - Comparison of the kinetic interactions of the neuroleptics perphenazine and
      zuclopenthixol with tricyclic antidepressives.
AB  - Using data from a therapeutic drug monitoring database, kinetic interactions
      between the neuroleptics zuclopenthixol and perphenazine and tricyclic
      antidepressives were studied. Out of 290 patients monitored for amitriptyline and
      611 patients monitored for nortriptyline, 77 patients were comedicated with
      perphenazine and 50 patients with zuclopenthixol. Comedication with perphenazine
      increased the median steady-state serum concentration to daily dose ratio (C/D)
      of nortriptyline by 30-45%, whereas the median C/D of amitriptyline was
      unaffected. On the contrary, median C/D values of nortriptyline and amitriptyline
      were not significantly influenced by comedication with zuclopenthixol. Thus, in
      accordance with previous studies, perphenazine increases the concentration of
      tricyclic antidepressives to a moderate extent. Zuclopenthixol, on the other
      hand, does not exert any impact under routine therapeutic drug monitoring, even
      though the drug is known to partly depend on metabolism by the isozyme cytochrome
      P450 2D6.

PMID- 7624930
TI  - Possible interaction between acyclovir and antiepileptic treatment.
AB  - We report a clinically relevant suspected interaction between acyclovir and the
      antiepileptic drugs phenytoin (PHT) and valproic acid (VPA). In a child receiving
      PHT and VPA therapy, a 6-day acyclovir treatment reduced PHT and VPA plasma
      concentrations to subtherapeutic values. This probably worsened both clinical
      status and electroencephalographic recordings observed in this patient. We
      suggest that the interaction occurs at gastrointestinal level with a reduction of
      PHT and VPA oral bioavailability during antiviral treatment.

PMID- 7624931
TI  - Specimen storage and amiodarone quality assurance.

PMID- 7624932
TI  - Circulating endotoxins and postreperfusion syndrome during orthotopic liver
      transplantation.

PMID- 7624933
TI  - Hepatic rejection after orthotopic liver transplantation for hepatic veno
      occlusive disease or graft-versus-host disease following bone marrow
      transplantation.

PMID- 7624934
TI  - Congenital right hepatico-diaphragmatic venous anastomosis discovered during a
      liver transplant resulting in a fatal outcome.

PMID- 7624935
TI  - Parameters in brain death in pigs.

PMID- 7624937
TI  - Cold ischemia-reperfusion injury of the liver. Role of the liver donor
      nutritional status in rats.
AB  - To verify the role of donor nutritional status on the quality of liver
      preservation after cold storage, we assessed hepatocyte and liver endothelial
      cell viabilities and functions in an isolated perfused rat liver model. Livers
      from fed and fasted Wistar rats were isolated and perfused either immediately
      after liver harvesting or after a 24-hr cold (4 degrees C) preservation in
      University of Wisconsin solution. Hyaluronic acid (150 ng/ml) and taurocholate
      (11.5 micrograms/ml) were infused into the reservoir, and their eliminations were
      assessed to evaluate liver endothelial cell function and hepatocyte function,
      respectively. Liver viability was estimated by intrahepatic resistance, oxygen
      consumption, bile secretion, and lactate dehydrogenase release. In addition, cell
      viabilities were evaluated by trypan blue staining. In fed-rat livers, glycogen
      content did not differ before or after the cold preservation, although a
      reduction was observed during the subsequent perfusion period. Liver glycogen
      content in fed rats was markedly higher than in the fasted rats at each time
      point studied. In fasted and fed rats, liver viability parameters and hepatocyte
      function were moderately altered, whereas liver endothelial cell function was
      markedly impaired after cold preservation. However, feeding had no influence on
      either hepatocyte or liver endothelial cell functions which were similarly
      altered in both nutritional conditions. The present data show that the
      nutritional status of liver donors does not play an important role in the
      preservation of liver endothelial cells after cold ischemia-reperfusion and,
      thus, should not affect the overall resistance of livers to hypothermic-ischemic
      injury.

PMID- 7624936
TI  - HLA-B44-restricted minor antigen.

PMID- 7624938
TI  - Secondary organ allografting after a primary "bridging" xenotransplant.
AB  - It remains uncertain whether xenotransplantation can sensitize the recipient to
      alloantigens, rendering subsequent allotransplantation unsuccessful. This is of
      considerable importance if a xenograft is to be used as a "bridge" to support the
      patient until a suitable allograft becomes available. When sera from 9 baboons
      that had received pig or African green monkey heart or liver xenografts were
      tested against a panel of lymphocytes from 5 or 6 potential donor baboons,
      positivity was seen in only 1 baboon (and then to only 2 of the potential 5
      donors). In 4 baboons that had undergone previous xenotransplants (1 from this
      series of 9 baboons and 3 others), subsequent organ allografting was not followed
      by hyperacute, antibody-mediated, or accelerated cellular rejection. We conclude
      that organ xenotransplantation using discordant or concordant donor species does
      not prohibit subsequent allotransplantation.

PMID- 7624939
TI  - Amlodipine improves hepatic hemodynamic and metabolic function in the isolated
      perfused rat liver after sequential cold and warm ischemia.
AB  - Amlodipine, a long acting calcium antagonist, was used to reduce the adverse
      effects of ischemic/reperfusion injury studied in isolated perfused rat livers.
      Amlodipine (10 mumol/L) was added to University of Wisconsin (UW) solution in
      which the liver was stored for 24 hr at 4 degrees C and incorporated in the
      saline flush used to displace the UW solution before 20 min of warm ischemia (at
      37 degrees C) and reperfusion. Initial median blood flow at 15 min was
      significantly higher after amlodipine treatment (2.78 vs. 1.41 ml/min/g of liver
      without amlodipine treatment, P = 0.013) as was the area under the curve of blood
      flow for the entire 3-hr perfusion (472 vs. 316 ml/g of liver, P = 0.003).
      Amlodipine treatment induced corresponding increases in oxygen delivery (1302 vs.
      896 mumol of O2/g of liver over 3 hr of perfusion, P = 0.003) and oxygen
      consumption (279 vs. 242 mumol of O2/g of liver over 3 hr, P = 0.06). Initial
      bile flow at 15 min was increased 4-fold by amlodipine treatment (17.27 vs. 4.59
      mg/hr/g of liver for sequential cold and warm ischemia, P = 0.013), and the
      median area under the curve of bile flow for the entire perfusion increased to
      92.2 vs. 53.9 mg/g of liver (P = 0.0006). Amlodipine treatment also reduced
      glucose release into the perfusate (116 vs. 149 mmol/L/g of liver min over 3 hr,
      P = 0.03) and prevented hepatocyte injury by reducing alanine aminotransferase
      release both initially (0.43 vs. 0.96 IU/L/g of liver, P = 0.055) and overall
      (343 vs. 797 IU/L/g of liver min, P = 0.048). When amlodipine was added only to
      the UW solution, blood flow increased by 66% initially (P = 0.02) and 32% overall
      (P = 0.013), but there was no corresponding improvement in hepatic function.
      Amlodipine may reduce hepatic ischemic/reperfusion injury by cytoprotective
      effects on parenchymal and non-parenchymal hepatocytes during both preservation
      and reperfusion leading to an improvement in liver microcirculation and an
      inhibition of the release of toxic mediators.

PMID- 7624940
TI  - Renal dysfunction in acute rejection. Effect of HLA typing, therapy, and
      histology.
AB  - Acute rejection is a frequent cause of early graft dysfunction in renal
      transplantation, and serum creatinine is the most important measure of clinical
      response. However, there is little information on serum creatinine during
      rejection episodes. In this study, the determinants that might influence the
      clinical response of serum creatinine during acute rejection were evaluated in 96
      renal transplant recipients with 100 episodes of biopsy-proven rejection, by
      univariate and multivariate analysis. The factors assessed for their influence on
      serum creatinine in acute rejection included: presence and severity of vascular
      or cellular rejection on biopsy, time taken to institute therapy, HLA mismatch,
      and the use of OKT3. The presence of vascular rejection on biopsy (n = 28) was a
      major determinant of impaired reciprocal area under the curve (AUC) of serum
      creatinine (P < 0.01), and was correlated with HLA-A and -B mismatch (r = 0.21, P
      < 0.05). Acute rejection associated with HLA-DR mismatch resulted in a more rapid
      increase of serum creatinine, a higher maximal creatinine, and a greater AUC
      creatinine (all P < 0.05). Treatment of acute rejection with OKT3 had a
      beneficial effect on AUC creatinine (P < 0.05) when compared with intravenous
      corticosteroids, by multivariate analysis. However, vascular rejection and HLA-DR
      mismatch had no effect on serum creatinine 1 year after transplantation. The
      biopsy cellular rejection score had no effect on AUC creatinine, although there
      was a modest effect on gradient of creatinine prior to biopsy. A minor adverse
      effect of delay in therapy of acute rejection could be demonstrated in the
      methylprednisolone-treated subgroup. In summary, HLA-DR mismatch and the presence
      of vascular rejection were the most important predictors of the severity of
      rejection assessed by the response of serum creatinine to treatment. Appropriate
      antirejection therapy should be instituted promptly to optimize clinical response
      during acute rejection.

PMID- 7624941
TI  - Extracorporeal photochemotherapy as adjuvant treatment of heart transplant
      recipients with recurrent rejection.
AB  - Recurrent rejection is an uncommon, severe complication after heart
      transplantation that is associated with a poor long-term prognosis. Photopheresis
      (ECP), a new form of extracorporeal photo-chemotherapy used for the treatment of
      cutaneous T cell lymphoma and several autoimmune diseases, has also been used for
      prevention and treatment of acute rejection in heart transplant recipients. It
      seems to induce specific suppression of both cellular and humoral rejection. In
      this study, we evaluated whether ECP added to standard therapies allowed better
      control of rejection and reduction of conventional immunosuppressive drugs in
      patients with repeated rejection episodes. Eight heart transplant recipients (6
      men and 2 women, mean age 48 yr), with recurrent rejection were treated with ECP
      for 6 months. Endomyocardial biopsies (EMB) were performed monthly. As a result
      of treatment, 7 patients on ECP experienced a reduction of the number and
      severity of rejection episodes. The fraction of EMB negative for rejection
      increased from 13 to 41%, whereas the fraction of specimens with multifocal
      and/or diffuse moderate lymphocytes infiltration (grades 3A and 3B) decreased
      from 41 to 21%. ECP allowed reductions of daily immunosuppressive therapy:
      prednisone by 44% (16.9 vs. 9.4 mg), cyclosporine by 21% (366 vs. 291 mg), and
      azathioprine by 29% (137 vs. 97 mg). No major side effects were observed. We
      conclude that, although the number of patients is small, the use of ECP was safe
      and associated with improved control of recurrent rejection. This allowed
      tapering of immunosuppressive drugs, which was particularly useful in two
      patients with insulin-dependent diabetes and one with sternal wound
      osteomyelitis.

PMID- 7624942
TI  - Backgrounds of early intragraft immune activation and rejection in liver
      transplant recipients. Impact of graft reperfusion quality.
AB  - In solid organ transplantation, acute rejections are most frequent during the
      first weeks. The aim of this study was to investigate the relationship between
      graft reperfusion injury and later immune responses against the graft. Intragraft
      immune activation was routinely monitored by transplant aspiration cytology in 47
      recipients of hepatic allografts. As a parameter of reperfusion quality, oxygen
      saturation of hemoglobin (SO2) in hepatic tissue was determined intraoperatively
      by a near-infrared spectroscopy. Grafts that presented aspiration cytology scores
      of 2 or more (i.e., more than 10% of lymphocytes activated) at 1 week after
      operation (group I, n = 14) were associated with a higher heterogeneity of
      hepatic tissue SO2 at the end of operation (coefficient of variation in 12 points
      18.3 +/- 18.3%, mean +/- SD) than grafts with no or very mild intragraft immune
      activation (group II, n = 33, 9.2 +/- 4.2%; P < 0.01). Group I was also
      accompanied by higher postoperative peak glutamic oxalacetic transaminase level
      (corrected by graft size, P < 0.05) and higher donor age (43.9 +/- 12.9 vs. 32.6
      +/- 13.9 years, P < 0.02). Heterogenous reperfusion (P < 0.01), higher peak
      glutamic oxalacetic transaminase level (P < 0.01), and higher donor age (P <
      0.05) were also associated with clinical rejection at 1 week (n = 10), but not
      with later-onset rejection (n = 11). These data suggest that intragraft immune
      activation and clinical rejection in the early phase after hepatic engraftment
      are strongly influenced by graft injury, which can be recognized early after
      reperfusion.

PMID- 7624943
TI  - A toxicity study of trimetrexate used in combination with cyclosporine as acute
      graft-versus-host disease prophylaxis in HLA-mismatched, related donor bone
      marrow transplants.
AB  - This study evaluated the acute toxicity of trimetrexate (TMTX) used in
      combination with cyclosporine (CsA) for prevention of acute graft-versus-host
      disease (GVHD) in patients undergoing allogeneic marrow transplantation from HLA
      mismatched, related donors. TMTX has a mechanism of action similar to that of
      methotrexate (MTX); however, unlike MTX, TMTX is not primarily dependent on renal
      excretion. Patients were conditioned for transplant with cyclophosphamide, anti
      thymocyte globulin, and total body irradiation. TMTX, 10 mg/m2 i.v., was
      administered on days 1, 3, 6, 11, 18, 25, 32, and 39 after transplant. CsA, 1.5
      mg/kg i.v., was administered every 12 hr beginning on day-1. Eleven patients with
      hematologic malignancies or aplastic anemia (median age = 34 yr) received TMTX.
      Toxicity assessed included nausea, vomiting, fever, rash, time to myeloid and
      platelet engraftment, mucositis, and hepatic and renal dysfunction. Toxicity of
      TMTX was not different from that observed with MTX in a similar patient
      population. One patient died on day 16 before engraftment. The other 10 patients
      all engrafted and all developed acute GVHD at a median time of 11 days after
      transplant. The major manifestation of acute GVHD was in the skin, and all but
      one patient responded to primary therapy with corticosteroids. Seven patients
      have survived a median of 447 days after transplant. No significant toxicity from
      TMTX was observed. Further trials are warranted to define the role of TMTX in
      marrow transplantation.

PMID- 7624945
TI  - Demonstration of cells possessing tolerance-inducing activity in Xenopus laevis
      rendered tolerant perimetamorphically.
AB  - J-strain (JJ) Xenopus laevis is easily made tolerant to semixenogeneic (X laevis
      x X borealis: JB) adult skin grafted onto immunologically competent larvae at
      stages 53-54. If the larvae are thymectomized shortly before skin grafting (late
      Txd), tolerance will never be induced. This suggests that suppression of the
      immune response to JB skin is mediated by a population of thymus-derived cells.
      In an attempt to confirm the presence of these cells, the spleen and tolerated JB
      skin were tested for their tolerance-inducing activity, by grafting either spleen
      or skin and a new JB skin piece simultaneously to late Txd JJ larva (secondary
      host). The results clearly indicated that both spleen and skin possessed the
      ability to induce tolerance. The injection of 1 x 10(5) splenocytes resulted in
      induction of tolerance in more than 80% of secondary hosts, and the rate of
      tolerance induction increased in relation to the injected cell number.
      Furthermore, tolerance was induced in about 90% of the animals by injecting as
      few as 100 cells isolated from the tolerated skin. Immunohistochemical
      observation of grafted skin showed that many host-derived T cells were
      distributed around the epidermal basal lamina. These results indicate that the
      cells with suppressive activity are a population of T cells that have
      differentiated in metamorphosing thymuses and have been released peripherally.

PMID- 7624944
TI  - Mixed xenogeneic chimerism and tolerance III. A nonlethal approach to induce
      donor-specific transplantation tolerance to simultaneous islet xenografts.
AB  - Previously, we reported that transplantation of rat bone marrow into lethally
      irradiated (950 rads) mouse recipients results in stable xenogeneic (rat-->mouse)
      chimerism and confers donor-specific transplantation tolerance for subsequent or
      simultaneous islet xenografts. For potential clinical application of chimerism to
      induce tolerance, it would be important to avoid the morbidity and mortality
      associated with lethal conditioning. Recently, we established a model to achieve
      durable multilineage xenogeneic chimerism using a nonlethal cytoreductive
      approach. We report here for the first time that donor-specific rat islet
      xenografts placed coincident with the bone marrow transplant are permanently
      accepted by nonlethally conditioned recipients. All recipients conditioned with
      700 cGy of total body irradiation and transplanted with 40 x 10(6) F344 rat bone
      marrow cells repopulated as mixed donor/host chimeras. The chimeras exhibited
      permanent acceptance of donor islet xenografts, since donor-specific F344 (Rt1A1)
      rat islet xenografts were significantly prolonged (median survival time > 110
      days), while MHC-disparate third-party WF (Rt1Au) rat islets were prolonged but
      rejected (median survival time = 33.2 days). The islets were functional to
      maintain normoglycemia and regulated in function to respond to an intraperitoneal
      glucose challenge. These data suggest that tolerance to donor-specific islet
      xenografts placed coincident with bone marrow transplantation can be achieved
      after nonlethal conditioning.

PMID- 7624946
TI  - Prolongation of rat islet allograft survival by treatment with monoclonal
      antibodies against VLA-4 and LFA-1.
AB  - In this study, we investigated the effects of treatment with monoclonal
      antibodies against the VLA-4 and LFA-1 adhesion molecules on rat islet allograft
      rejection. TA-2 and TA-3 are function-blocking mAb against rat VLA-4 and LFA-1,
      respectively. Lewis rats were made diabetic (plasma glucose levels > 22.2 mmol/L)
      with streptozotocin. One week later, 1500 freshly isolated Wistar Furth rat
      islets were transplanted under the left kidney capsule of each rat. Monoclonal
      antibodies were administered intravenously at a dosage of 2 mg on the day of
      islet transplantation and then intraperitoneally every second day for 3 weeks or
      until graft rejection. Plasma glucose levels were monitored at least 3 times a
      week and blood leukocyte counts were monitored every 4 days. Rejection was
      defined as 2 plasma glucose levels > 11.1 mmol/L. Mean graft survival times in
      untreated and control mAb-treated rats were 5.3 and 6.0 days, respectively.
      Treatment with anti-VLA-4 or anti-LFA-1 resulted in only modest prolongation of
      mean graft survival time (9.3 and 7.4 days, respectively). However, treatment
      with the combination of anti-VLA-4 plus anti-LFA-1 resulted in long-term (i.e.,
      60-day) graft survival in 5 of 7 rats. Graft nephrectomy and histology confirmed
      islet graft survival at 60 days. A second Wistar Furth rat islet graft under the
      opposite renal capsule after graft nephrectomy did not show full tolerance;
      however, the function of the second graft was significantly prolonged without any
      immunosuppression. Combined blockade of VLA-4 and LFA-1 also markedly prolonged
      islet graft survival when islets were transplanted via the portal vein. In
      conclusion, both VLA-4 and LFA-1 play a role in islet allograft rejection and
      blockade of both prevents or greatly delays graft rejection.

PMID- 7624948
TI  - Allogeneic lymphocyte proliferation stimulated by small intestine-derived
      epithelial cells.
AB  - It has been more difficult to prevent intestinal allograft rejection than
      rejection of other solid organ transplants. Epithelial cells in the small
      intestine have the potential to actively participate in graft rejection because
      they constitutively express MHC class II antigens. The present study examined the
      ability of intestinal epithelial cells (IEC) to stimulate allogeneic T cells in
      vitro using one-way MLC. IEC from jejunum and ileum of ACI rats (RT1a) were used
      as the stimulator cells; purified T lymphocytes from Lewis rats (RT11) were used
      as the responder cells. Freshly isolated IEC were poor stimulators of naive
      allogeneic T lymphocytes. However, IEC induced a strong proliferation of primed
      allogeneic T lymphocytes, and this response could be blocked by anti-MHC class II
      mAb (OX-4). IEC stimulated a vigorous proliferation of naive T cells when co
      cultured with (1) macrophages syngeneic with responder T lymphocytes, (2)
      supernatants of LPS-stimulated macrophages, or (3) a combination of IL-1 and IL
      6. We conclude that MHC class II positive IEC require soluble costimulatory
      factors to fully activate naive allogeneic T cells. Immune stimulation by
      enterocytes may be one of the reasons why it is so difficult to prevent
      intestinal allograft rejection. Strategies that block interactions among IEC,
      macrophages, and lymphocytes may reduce the immunogenicity of small bowel
      transplants.

PMID- 7624947
TI  - Selective inhibition of nitric oxide production during cardiac allograft
      rejection causes a small increase in graft survival.
AB  - Nitric oxide production is increased in allograft rejection and may have both
      beneficial and deleterious effects on graft function and survival. In animal
      models, conventional immunosuppressive agents have been shown to decrease nitric
      oxide production. The aim of our study was to determine what effect augmentation
      and selective inhibition of nitric oxide production may have on graft survival by
      using the model of heterotopic cardiac transplantation in the rat. L-Arginine,
      the naturally occurring substrate for nitric oxide production, was administered
      subcutaneously at 200 mg/kg/day. L-NG-monomethyl-L-arginine (L-NMMA) is a
      selective inhibitor of nitric oxide synthase and was administered at 500
      mg/kg/day to allograft recipients from the day of operation. Endogenous nitric
      oxide production was quantified by analysis of urinary nitrate excretion, and
      time to rejection was determined by graft palpation. L-Arginine did not
      significantly alter urinary nitrate excretion by iso- or allografts, suggesting
      that nitric oxide production is not a substrate-limited process in this model.
      Graft survival in this group was unchanged. L-NMMA produced a small increase in
      graft survival from 5.1 +/- 0.1 to 6.3 +/- 0.3 days compared with control
      allografts (P = 0.001) and abolished the rise in urinary nitrate excretion seen
      with control allografts. Lower doses of L-NMMA produced dose-related decrements
      in urinary nitrate excretion, but did not alter graft survival. We found that
      allograft rejection can proceed to graft loss despite complete inhibition of the
      increase in nitric oxide production that occurs during untreated rejection. The
      small increase in graft survival suggests that nitric oxide plays a minor role as
      a cytotoxic effector molecule in this model of acute rejection.

PMID- 7624949
TI  - Combined antagonism of endothelin A/B receptors links endothelin to
      vasoconstriction whereas angiotensin II effects fibrosis. Studies in chronic
      cyclosporine nephrotoxicity in rats.
AB  - Both functional and structural damage characterize nephrotoxicity due to
      cyclosporine (CsA) with accumulating evidence for dissociation of mechanisms that
      lead to each of these processes. We studied the role of endothelin (Et) and
      angiotensin II (AII), since each of these peptides can modulate vasoconstriction
      as well as parenchymal destruction. Salt-depleted rats were treated with daily
      CsA (15 mg/kg s.c.) for 5 weeks (group 1, CsA, n = 13). Separate groups of CsA
      treated rats received either a combined antagonist of both EtA/EtB receptors
      (group 2, CsA+aEtA/B, 100 mg/kg/day p.o., n = 6) or angiotensin I-converting
      enzyme inhibitor (group 3, CsA+ACEI, enalapril 200 mg/L drinking water, n = 8).
      Glomerular filtration rate (GFR) was assessed by creatinine clearance (Ccr) in
      conscious rats at 3 and 5 weeks. At 3 weeks, serum creatinine was 1.5 +/- 0.1
      mg/dl in group 1 rats, 1.2 +/- 0.2 mg/dl in group 2 rats (P < 0.05 vs. CsA), and
      2.3 +/- 0.8 mg/dl in group 3 rats. Ccr was 0.87 +/- 0.08 ml/min in group 1. In
      group 2, GFR was remarkably preserved (1.14 +/- 0.11 ml/min, P < 0.05 vs. group
      1). By contrast, GFR in group 3 rats was lower (0.31 +/- 0.08 ml/min) than either
      aEtA/B-treated or even CsA-treated rats (P < 0.0005 vs. group 1, P < 0.0005 vs.
      group 2). At 5 weeks, the same pattern emerged; serum creatinine was 2.5 +/- 0.2
      mg/dl in group 1, 1.2 +/- 0.1 in group 2 (P < 0.0005 vs. CsA), and 3.4 +/- 0.9 in
      group 3 (P < 0.025 vs. CsA+aEtA/B). Ccr had decreased dramatically in CsA-treated
      rats to 0.18 +/- 0.03 ml/min. GFR was preserved in CsA+aEtA/B rats (0.51 +/- 0.03
      ml/min, P < 0.0005 vs. group 1), while profound hypofiltration was apparent in
      CsA+ACEI rats (0.12 +/- 0.03 ml/min, P < 0.0005 vs. group 2). In salt-depleted
      control animals, GFR was 0.62 +/- 0.02 ml/min. Despite striking functional
      preservation in response to antagonism of Et receptors, tubular
      vacuolization/dilatation, as well as arteriolopathy, was not different among the
      CsA-treated groups. Tubulointerstitial fibrosis was also not different between
      CsA and CsA+aEtA/B rats (on a 0-4 scale, 1.05 +/- 0.14 vs. 0.87 +/- 0.14, P =
      NS). In contrast, both tubular vacuolization/dilatation and interstitial fibrosis
      were significantly greater in all CsA-treated groups compared with salt-depleted
      controls. However, in the CsA+ACEI group that had the most severe hypofiltration
      at each time point, tubulointerstitial fibrosis was 0.69 +/- 0.06 (P < 0.05 vs.
      CsA).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7624950
TI  - Establishment of canine pulmonary hypertension with dehydromonocrotaline.
      Importance of larger animal model for lung transplantation.
AB  - Single lung isografting in rats with pulmonary hypertension has been reported.
      However, it is hard to evaluate cardiopulmonary hemodynamics accurately or to use
      circulatory assists during procedures using rats. Therefore, we tried to
      establish a model of pulmonary hypertension in the beagle. Twenty young beagles
      were randomized into 3 groups. An injection of dehydromonocrotaline of 1.5 mg/kg
      (group 1, n = 7), 3.0 mg/kg (group 2, n = 10), or 4.5 mg/kg (group 3, n = 3) was
      performed via the right atrium. Two dogs in group 2 and all the dogs in group 3
      died of acute pulmonary edema. During the 8 weeks after injection, the systolic
      pulmonary arterial pressure and pulmonary vascular resistance index increased
      significantly in group 2 from 21 +/- 2 to 56 +/- 9 mmHg and from 106 +/- 39 to
      826 +/- 176 dynes.sec.cm-5.m2, respectively (P < 0.01). The changes in group 1
      were less pronounced. The dogs in group 2 also had a rise in their plasma
      endothelin-1. Pathologic analysis revealed thickening of the media in small
      pulmonary arteries and hypertrophy of the right ventricular myocardium. Our data
      indicate that beagles treated with 3.0 mg/kg dehydromonocrotaline produced a
      unique, relatively noninvasive model of pulmonary hypertension. In the model,
      right ventricular failure prevented us from clamping one pulmonary artery. These
      relatively large animals with pulmonary hypertension will be valuable for further
      studies of lung transplantation.

PMID- 7624951
TI  - Endothelial loss and regeneration in a model of transplant arteriosclerosis.
AB  - Early endothelial injury may play a role in the development of transplant
      arteriosclerosis. The present study documents early endothelial changes using a
      rat aortic graft model. Abdominal aortic allografts from PVG rats were
      orthotopically transplanted to DA rats. Controls were DA to DA transplants.
      Endothelial cell (EC) injury, regeneration, and leukocyte infiltration in the
      intima were evaluated using scanning electron microscopy and histological and
      immunocytochemical techniques. Nontransplanted aortic segments showed partial
      loss of ECs after 1 or 2 hr of preservation. Control isografts demonstrated
      extensive EC denudation and neutrophil adherence to residual ECs at 1 day post
      transplantation. After 3 days, isografts showed continued regeneration of ECs in
      the central area and ingrowth of endothelium from both clamped sites in the
      recipient aorta. Reendothelialization was complete by day 14. Allografts showed
      similar findings to isografts up to day 3. In contrast to isografts, however,
      there was a secondary EC loss beginning at day 7. Monocytes/macrophages and T
      cells were noted to be adherent to residual ECs in 7- and 14-day allografts. At
      20 days, ECs were absent from the luminal surface in the center of allografts.
      Endothelium did extend from clamped sites toward the midgraft region as in
      isografts. By 60 days allografts were completely reendothelialized. These results
      demonstrate that in both isografts and allografts there is initial EC loss due to
      mechanical trauma and ischemia/reperfusion injury, followed by partial
      reendothelialization. This latter process continues unabated in isografts,
      whereas in allografts the secondary EC loss occurs due to an allogenic response.
      This is followed by complete reendothelialization that occurs during the
      concurrent development of significant intimal hyperplasia.

PMID- 7624952
TI  - The role of cyclosporine-induced autoreactive T lymphocytes in solid organ
      allograft survival and chronic rejection.
AB  - Cyclosporine (CsA) has profound but paradoxical effects on the immune system. CsA
      can facilitate the induction of transplantation tolerance in some animal systems
      but it inhibits the clonal deletion of MHC class II autoreactive T cells. The
      present studies evaluated whether the autoreactive T cells participate in the
      induction of facilitated graft acceptance after CsA treatment by recognizing and
      eliminating activated allograft responsive T cells that express MHC class II
      determinants. Transfer of autoreactive T cells into naive Lewis rats pretreated
      with cyclophosphamide significantly prolonged the survival of heterotopic cardiac
      allografts from MHC-disparate BN strain donors. Following transfer of the
      autoreactive T cells, there was a marked reduction in the frequency of
      alloreactive T lymphocytes responsive to donor alloantigens. The role of MHC
      class II autoreactive CD8+ V beta 8.5+ T cells in facilitated graft acceptance
      was also supported by the findings that (1) treatment with anti-MHC class II
      antibody abrogated prolonged allograft survival after CsA therapy and (2) V beta
      8.5+ lymphocytes infiltrate the allograft during CsA therapy but are absent in
      the graft in non-CsA-treated control animals. Although these data are consistent
      with the hypothesis that autoreactive T cells prolong cardiac allograft survival
      after CsA treatment, the autoaggressive cells failed to inhibit the development
      of chronic rejection of both heart and skin allografts. These data suggest either
      that the autoreactive T cells do not inhibit immune mechanisms responsible for
      chronic graft rejection or that the autoaggressive lymphocytes may participate in
      and exacerbate chronic rejection of allografts. Taken together, the induction of
      MHC class II autoreactive T cells may provide a common fundamental mechanism
      explaining the paradoxical effects of CsA.

PMID- 7624953
TI  - Heteroagglutinins and their significance in baboon hepatic xenotransplantation.
AB  - The role of preformed xenoreactive antibodies in xenograft recipients is unknown.
      Humans and baboons possess red cell agglutinating activity associated with
      isohemagglutinins and heteroagglutinins (HA). We examined the role of HA in two
      patients who received ABO-identical baboon livers. Human antibaboon HA were
      assessed by correlating serial titers with studies for rejection. Serial direct
      antiglobulin testing (DAT) was used to detect baboon antihuman HA, potentially
      produced by transplanted passenger lymphocytes. Patient 1 survived 70 days. The
      human antibaboon HA titers remained essentially unchanged from preoperative
      values. Although hyperacute rejection did not occur, and there was only mild
      cellular rejection, liver function was suboptimal. Postreperfusion immunoglobulin
      and complement deposition and histologic changes suggested complement-mediated
      injury. DAT testing was negative except for passively acquired anti-A from
      transfusion. At autopsy there was marked bile stasis, but no rejection. Patient 2
      survived 26 days with essentially unchanged HA titers until preterminal. Although
      there was no hyperacute rejection and only mild humoral rejection (without
      cellular rejection), suboptimal liver function and bile stasis were again noted.
      Postreperfusion immunoglobulin and complement deposition again suggested
      complement-mediated injury. DAT testing was negative. At autopsy there was no
      rejection. Human antibaboon HA do not appear to be associated with hyperacute or
      cellular rejection, but their role in the complement-mediated injury, suspected
      in both cases, cannot be definitively excluded. Baboon antihuman HA were not
      detected in either patient.

PMID- 7624954
TI  - Angiotensin-converting enzyme inhibition in the treatment of renal transplant
      erythrocytosis. Clinical experience and observation of mechanism.
AB  - Recent observations indicate that angiotensin-converting enzyme (ACE) inhibition
      corrects renal transplant erythrocytosis (RTE). The mechanism for this
      association is not known. We examined the effect of ACE inhibition on hematocrit,
      erythropoietin (EPO), and renin substrate. ACE inhibition has been reported to
      suppress renin substrate, which is known to stimulate EPO and erythropoiesis. In
      15 patients with RTE, hematocrit dropped from 52.8 +/- 0.6 (SEM) to 45.8 +/- 1.4%
      after 8 weeks of treatment with Enalapril, 2.5-20 mg/day. Serum EPO (normal
      range: 9-30 mU/ml) was high in one, normal in seven, and low in seven patients.
      ACE inhibition reduced EPO in patients with initial high or normal levels but
      induced no change in patients with initial low levels. ACE inhibition had no
      significant effect on renin substrate. In one patient who rejected his first
      graft, erythrocytosis recurred following a second, successful transplant.
      Treatment was discontinued because of cough in two patients and symptomatic drop
      in blood pressure in one patient. We conclude RTE is not caused by
      hypererythropoietinemia. In patients with normal circulating EPO, erythrocytosis
      may result from an increase sensitivity to EPO, and ACE inhibition lowered
      hematocrit by further reduction of this hormone. However, the finding of
      erythrocytosis in half our patients with suppressed EPO, suggests the
      participation of non-EPO-mediated mechanism(s). The recurrence of RTE in a
      patient after a second transplant raises the additional possibility of patient
      specific factors in the pathogenesis of this disorder. In contrast to other
      reports, we documented side-effects (cough, hypotension) in three (20%) of our
      patients. Our clinical experience, coupled with prior reports of spontaneous
      resolution of RTE in some patients, suggests that intermittent courses of ACE
      inhibition may be the optimal strategy in the use of this form of therapy for
      RTE.

PMID- 7624955
TI  - Risk factors affecting second renal transplant outcome, with special reference to
      primary allograft nephrectomy.
AB  - Removal of a failed primary renal allograft was found by some groups to adversely
      affect the outcome of a second kidney transplant. Recent data does not support
      this view and fail to show any such effect. Such data, however, are limited by
      small numbers or univariate analysis. The records of 192 patients receiving a
      primary and a subsequent kidney transplant between January 1980 and July 1992
      were retrospectively reviewed. Immunosuppression initially included azathioprine
      and prednisone; cyclosporine was introduced in December 1983 with Minnesota
      antilymphocyte globulin (MALG) added for induction in May 1987. Regraft survival
      rates were 66% at one year and 60% at two years. Using Kaplan-Meier survival
      analysis patients having primary transplant nephrectomy had a worse second
      allograft outcome than patients who kept their failed grafts (P = 0.0003).
      Multivariate analysis showed a significant relationship between primary allograft
      survival and retransplant outcome. To eliminate this influence, patients whose
      first graft failed within six months of transplantation were excluded from the
      analysis. This resulted in 90 patients whose first graft functioned for more than
      6 months. Graft survival was 80% at one year and 73% at 2 years in this select
      population. Patients with prior transplant nephrectomy still had a worse
      retransplant outcome than those who kept their failed grafts (P = 0.05).
      Multivariate analysis identified primary allograft nephrectomy, older donor age,
      longer interval from nephrectomy to retransplant, and lack of MALG at induction
      as negative risk factors. In conclusion, primary allograft nephrectomy may have a
      negative influence on second renal transplant outcome. This result may be
      improved by reducing donor age and the time interval from nephrectomy to
      retransplantation, and using MALG at induction.

PMID- 7624956
TI  - Fibrin clot lysis by tissue plasminogen activator (tPA) is impaired in plasma
      from pediatric patients undergoing orthotopic liver transplantation.
AB  - Large vessel thrombi can present life-threatening complications following
      orthotopic liver transplantation (OLT) in pediatric patients. We investigated the
      thrombolytic response to tissue plasminogen activator (tPA) of stored, pooled
      plasma (days 4-14 postoperatively) from 41 patients (mean age 4 years, 9 months)
      who underwent OLT at the Hospital for Sick Children, Toronto between 1986 and
      1990. Trace-labeled fibrin clots were prepared by recalcifying 500-microliters
      aliquots of patient plasma spiked with 125I fibrinogen and then incubated at 37
      degrees C in patient plasma in the presence or absence of tPA (0.1 or 0.3 mg/ml).
      At the end of the incubation period, the extent of clot lysis and concentrations
      of fibrinogen, plasminogen, and alpha 2 antiplasmin were determined. Pooled adult
      plasma was used as a control. Fibrin clot lysis in OLT plasma was significantly
      reduced compared with controls (P < 0.01). Initial concentrations of plasminogen
      were significantly reduced in OLT plasma. To determine if the low plasminogen
      levels limited the thrombolytic effect of tPA, we supplemented OLT plasma with
      purified plasminogen. Fibrin clots placed in OLT plasma containing adult levels
      of plasminogen showed a similar lytic response as adults. In summary, the reduced
      fibrinolytic response of OLT fibrin clots to tPA was due to low concentrations of
      plasminogen and corrected by plasminogen supplementation.

PMID- 7624957
TI  - The incidence of antibody formation to OKT3 consequent to its use in organ
      transplantation.
AB  - Enzyme-linked immunosorbent assays were performed on 12,133 serum samples to
      determine the incidence of anti-OKT3 antibody formation among transplant
      recipients who had received OKT3 for rejection treatment or prophylaxis. High
      anti-OKT3 antibody titers (> or = 1:1000) were detected in 5.8% of samples drawn
      2 to 8 weeks following initiation of OKT3 therapy. The frequency of high titers
      differed by organ (6.9%, 2.7%, and 5.3% for kidney, heart, and liver,
      respectively; P < 0.001) and by sampling times (P < 0.001). The highest frequency
      of positive titers was obtained in samples obtained between 2 and 4 weeks
      following the initiation of OKT3. For all transplant recipients and for kidney
      recipients alone, multivariate logistic regression showed that the risk of high
      anti-OKT3 titers varied significantly at 2 to 4 weeks and at 4 to 6 weeks (but
      not at 6 to 8 weeks) with age (the youngest patients had the highest incidence,
      with a steady decline after age 30; P < 0.05), course of therapy (lowest
      frequencies followed a first course of OKT3; P < 0.001), and transplant number
      (lowest frequencies followed a first transplant; P < 0.01). Analyses of a set of
      patients on whom immunosuppressive regimen information was available indicated
      that prophylactic or maintenance treatment with CsA was associated with a
      significantly lower frequency of high-titer anti-OKT3 antibodies than was therapy
      without CsA (P < 0.001). In conclusion, this series provides confirming evidence
      that high-titer anti-OKT3 antibodies, which are of concern whenever retreatment
      with OKT3 is contemplated, occur in a low percentage of patients and are
      associated with such factors as age, previous transplantation or courses of
      therapy with OKT3, and treatment with CsA.

PMID- 7624959
TI  - In vivo reactivity of T cell clones isolated from mice with syngeneic graft
      versus-host disease.
AB  - Syngeneic graft-versus-host disease (SGVHD) has been shown to occur in murine
      syngeneic radiation bone marrow chimeras following a short course of
      cyclosporine. To analyze the effector mechanisms present in diseased animals,
      four T cell clones (1D5, 1D8, 1C10, 2D8) were isolated from the spleens of
      C3H/HeN mice late in the disease course by cloning on irradiated syngeneic spleen
      cells. These clones were CD4+, alpha beta TCR+ and responded to I-Kk in vitro. In
      addition to I-Ek reactivity, three of the clones exhibited crossreactivity with
      the superantigen MIs 1a (mtv 7). Clones 1D5 and 1C10 were found to express TCR V
      beta chains (V beta 4 and V beta 8.1, respectively), which are normally present
      in the T cell repertoire of C3H/HeN mice. All SGVHD clones were found to be
      autoreactive in that they responded to syngeneic stimulator cells in the absence
      of xenogeneic serum proteins. To test in vivo activity, the 1D5 SGVHD clone was
      injected into the hind footpad of mice where it was shown to induce footpad
      swelling in a cell dose-dependent, I-Ek-specific manner in sublethally
      irradiated, but not normal mice. Histological analysis indicated that the clone
      induced dermal and subcutaneous edema that correlated directly with injection of
      1D5 and not the control clone. Preliminary experiments suggested that the other
      three autoreactive clones behaved in a similar manner. These data are consistent
      with the involvement of a self-class II-specific CD4+ T cell in murine SGVHD.

PMID- 7624960
TI  - A human model of xenogeneic graft-versus-host disease in SCID mice engrafted with
      human peripheral blood lymphocytes.
AB  - Despite previous attempts there is currently no suitable animal model available
      for xenogeneic graft versus host disease (XGVHD) mediated via human
      immunocompetent cells. Recently, we have developed an efficient protocol to
      engraft SCID mice with human peripheral blood lymphocytes (Hu-PBLs). The
      engraftment efficiency is extremely high, such that 100% of Hu-PBL-SCID mice die
      of XGVHD within 4 weeks after engraftment with Hu-PBLs (3-5 x 10(7) cells). A
      series of experiments was performed to investigate the mechanisms involved in the
      severe XGVHD. The results suggest that XGVHD was induced by human CD4+ T cells,
      antixenogeneic (antimouse) antibodies, and lymphokines. The SCID mouse model will
      be extremely valuable for the evaluation and development of immunosuppressive
      agents and transplantation protocols for human XGVHD.

PMID- 7624961
TI  - The differential effect of alloantigen-blocking antibodies on unprimed and memory
      T helper cells.
AB  - Responsiveness to recall antigens by memory and naive T helper cells is
      different. To study whether such a difference is also applicable to affinity for
      allorecognition, we analyzed the effect of an IgG MLR blocking antibody separated
      from sera of patients with known kidney transplant chronic rejection on primed
      and unprimed CD4+ T cell alloreactivity. The results show that addition of the
      IgG fraction inhibits the patient's own unprimed T helper cell responses to a
      panel of four different alloantigens as well as a third-party mixed lymphocyte
      response. The same IgG fraction inhibited third-party naive T helper cell, but
      not autologous unprimed T helper cell, proliferation to adherent anti-CD3
      antibody, which suggests that the mechanism of inhibitory action of the IgG is
      allogeneic-dependent. This IgG also did not induce inhibition of any of the T
      helper cell clone responsiveness, raised from the same or other patients, when
      stimulated with the same alloantigens used for unprimed cell alloactivation.
      Differential responses of naive and memory CD4+ T cells to alloantigens may
      explain some differences between the in vivo and in vitro systems and why
      allograft rejection can proceed in the presence of allogeneic blocking
      antibodies.

PMID- 7624958
TI  - Variable chimerism, graft-versus-host disease, and tolerance after different
      kinds of cell and whole organ transplantation from Lewis to brown Norway rats.
AB  - The bidirectional paradigm of tolerance involving reciprocal host vs. graft and
      graft vs. host reactions was examined after Lewis (LEW)-->Brown Norway (BN)
      transplantation of different whole organs (liver, intestine, heart, and kidney)
      or of 2.5 x 10(8) LEW leukocytes obtained from bone marrow, spleen, lymph nodes,
      and thymus. The experiments were performed without immunosuppression or under 14
      daily doses of postoperative tacrolimus, which were continued in weekly doses to
      100 days in a "continuous treatment" subgroup, and to 27 days in a short
      treatment group. Without immunosuppression, all organs and cell suspensions
      failed to engraft or were acutely rejected. GVHD (usually fatal) was always
      caused when either the long or short treatment was used for recipients of
      intestinal grafts and cell suspensions of spleen and lymph nodes. In contrast,
      both immunosuppressive protocols allowed engraftment of bone marrow cells, liver,
      heart, and kidney without clinical GVHD, whereas thymus cell suspensions and
      small doses of whole blood neither engrafted nor caused GVHD. At 100 days, now
      drug-free for 73 days, the liver, bone marrow, and heart recipients were tolerant
      in that they accepted all challenge LEW heart and/or liver grafts for 100 more
      days despite in vitro evidence of donor-specific reactivity (split tolerance). At
      200 days, histopathologic studies of the challenge livers were normal no matter
      what the priming graft. However, the still-beating challenge hearts had a
      spectrum from normal to severe chronic rejection that defined the tolerogenicity
      of the original primary grafts: liver best-->bone marrow next-->heart least. Both
      the GVHD propensity and tolerogenicity in these experiments were closely
      associated with recipient tissue chimerism 30 and 100 days after the experiments
      began. The tissue chimerism was invariably multilineage, but the GVHD outcome was
      associated with T cell over-representation. These observations provide guidelines
      that should be considered in devising leukocyte augmentation protocols for human
      whole organ recipients. The results are discussed in relation to the historical
      tolerance studies of Billingham, Brent, and Medawar; Good; Monaco; and Calne.

PMID- 7624962
TI  - CD45RC+ CD4 T cell subsets are maintained in an unresponsive state by the
      persistence of transfusion-derived alloantigen.
AB  - The ability of preoperative blood transfusion to extend the survival of organ
      allografts is well known but poorly understood. To study this phenomenon, adult
      PVG (RT1c) rats were rendered tolerant of DA (RT1a) cardiac allografts by prior
      donor-specific blood transfusion (DST). We investigated the cellular basis of the
      transfusion effect by adoptively transferring CD4 T cell subsets, obtained from
      thoracic duct lymph of tolerant rats, into cardiac allografted athymic PVG nude
      recipients. Surprisingly, CD4 T cells from DST rats evoked acute rejection on
      adoptive transfer. Evidence indicated that CD8 T cells played no role in DST
      induced tolerance. Analysis of CD4 T cell subsets, defined in the rat by mAb OX22
      (anti-CD45RC), revealed an unusual pattern of responsiveness. CD45RC+ CD4 T cells
      (normally capable of inducing prompt rejection), when obtained from rats given a
      specific blood transfusion, were depleted of alloreactive cells and deficient at
      inducing rejection. In contrast, the CD45RC- subset (normally slow at evoking
      graft destruction) was highly active and ten-fold-enriched in its ability to
      induce rejection. Destruction of cardiac allografts by this latter subset was,
      however, completely inhibited by giving nude recipients a specific (but not a
      third-party) blood transfusion two weeks before heart grafting and cell transfer.
      Apparently, tolerance was maintained by residual elements of the prior blood
      transfusion that prevented the specific CD45RC- subset from regaining an
      alloaggressive capacity.

PMID- 7624963
TI  - Quantitative estimation of intrasplenically transplanted hepatocytes in Gunn rats
      using technetium-99m-diethylenetriaminepentaacetic acid-galactosyl-human serum
      albumin.

PMID- 7624964
TI  - A new harvesting method prolongs survival of cardiac xenografts from guinea pig
      to rat.

PMID- 7624965
TI  - Cardiac rhabdomyosarcoma in a renal transplant patient.

PMID- 7624966
TI  - Yersinia enterocolitica septicemia in a renal transplant recipient on oral iron
      supplementation.

PMID- 7624967
TI  - Tolerance induction to multiple donor rat islet allografts by intrathymic
      inoculation of spleen cell membrane antigens.

PMID- 7624969
TI  - Does a radiolabelled ligand bind to a homogeneous population of non-interacting
      receptor sites?
AB  - Receptor subtypes of pharmacological interest are often characterized by studies
      in which a particular radiolabelled ligand is competitively displaced from its
      binding sites, either by its unlabelled analogue (homologous displacement), or by
      different, unlabelled, ligands (heterologous displacement). In this article,
      Stephane Swillens, Magali Waelbroeck and Philippe Champeil emphasize the fact
      that a single homologous displacement curve is generally unable to reveal that
      the radioligand binds to a heterogeneous receptor population. Overlooking this
      heterogeneity may, in turn, dramatically affect interpretation of heterologous
      displacement curves displaying more than one receptor type for the unlabelled
      ligand: neither the binding affinities of the ligands for the different
      receptors, nor the proportion of these receptors, can be estimated reliably.

PMID- 7624968
TI  - Fast electrochemical studies in isolated tissues.

PMID- 7624971
TI  - Functional domains of GABAA receptors.
AB  - The transmitter-gated ion channels mediate rapid synaptic transmission, for
      example, at the neuromuscular junction using acetylcholine and in the CNS using
      primarily the amino acids glutamate and GABA. GABAA-receptor Cl- channels share
      sequence homology with a superfamily of these channels including nicotinic
      acetylcholine receptor and inhibitory glycine receptor. In this article, Geoffrey
      Smith and Richard Olsen discuss recent affinity labelling and site-directed
      mutagenesis studies on GABAA receptors that have identified amino acid residues
      essential for binding of agonists and allosteric modulators as well as the ion
      channel wall formation. The structural domains identified are consistent with
      results obtained with other members of the transmitter-gated ion channel
      superfamily and suggest that structural models for one member of the family may
      apply to the others as well.

PMID- 7624970
TI  - Does the ternary complex act as a secondary proton pump and a GTP synthase?
AB  - It has been suggested that G protein-coupled receptors can act as proton
      transporters, with the activated G protein-coupled receptor transporting H+
      across the membrane from the extracellular side to the cytoplasm. In this
      article, Paul Nederkoorn, Henk Timmerman and Gabrielle Donne-Op den Kelder
      summarize the various H+ translocation mechanisms and how these compare with
      activated G protein-coupled receptors. The G protein, being part of the ternary
      complex, is proposed to use translocated protons to synthesize GTP from GDP and
      Pi, thus functioning in a similar manner to ATP synthase. The importance of these
      events in physiological effects such as signal amplification is discussed.

PMID- 7624972
TI  - How should P2X purinoceptors be classified pharmacologically?
AB  - When ATP is released as a neurotransmitter from central and peripheral nerves it
      acts at P2X purinoceptors to produce postsynaptic depolarization and excitation.
      The P2X purinoceptor was originally classified on the basis of the relative
      agonist potencies of ATP and a number of its structural analogues. However, it is
      now clear that the potency of some agonists is greatly decreased by breakdown by
      ectonucleotidase enzymes, leading to an incorrect determination of agonist
      potency order. In this article, Charles Kennedy and Paul Leff discuss recent
      results that indicate that the established classification of P2X purinoceptors is
      no longer valid and needs redefinition.

PMID- 7624974
TI  - [Treatment of ureteral stones with laser--75 cases].

PMID- 7624973
TI  - [Prevalence of endemic goiter in the north western region of Tunisia--1993].

PMID- 7624975
TI  - [Infertility in couples. Analytic study of 430 cases].

PMID- 7624976
TI  - [Complications of endotracheal intubation and tracheotomy. Retrospective study of
      797 cases].

PMID- 7624977
TI  - [Cutaneous manifestations of sarcoidosis: diagnostic problems].

PMID- 7624978
TI  - [Interatrial defects of the ostium secundum type operated on after the age of
      sixteen].

PMID- 7624979
TI  - [Cytological and immunochemical analysis of forty cases of multiple myeloma].

PMID- 7624980
TI  - [Acute myelopathy of tuberculous origin. Two cases].

PMID- 7624981
TI  - [Bordetella pertussis: a case of whooping cough in a newborn].

PMID- 7624982
TI  - [Horton's disease and hypothyroidism. A case report].

PMID- 7624983
TI  - Hormone-refractory (D3) prostate cancer: refining the concept.
AB  - OBJECTIVES: A wide range of responses have been reported to second-line hormonal
      therapies, including corticosteroids and the withdrawal of antiandrogens in
      patients with hormone-refractory prostate cancers. This suggested the need to
      classify patients on the basis of hormonal sensitivity. A schema was developed by
      assessing the differences in entry criteria in relation to outcomes for clinical
      protocols with hydrocortisone alone or in combination with other agents for
      patients who had progressed after primary hormone therapy. METHODS: Published
      clinical trials of patients who had progressed after primary hormone treatment,
      which included glucocorticoids, were retrieved from Medline listings. The trials
      included patients treated with hydrocortisone alone, hydrocortisone and
      aminoglutethimide, hydrocortisone plus suramin, dexamethasone, and prednisone
      alone or in combination with chemotherapy. RESULTS: The definitions used for
      refractory disease ranged from none, to "progression", to "unsuccessful second
      medical or surgical castration. "None of the trials included a definition for
      hormone-refractory disease based on objective criteria. Details were lacking on
      most trials with respect to the response to and specific types of hormonal
      therapies. Furthermore, few trials controlled for the potential contribution of
      the "flutamide withdrawal syndrome" on outcome. CONCLUSIONS: The term "hormone
      refractory" prostate cancer has evolved to include patients with a spectrum of
      diseases. As utilized in clinical trials of second-line hormonal therapies,
      patients who have received one and as many as six different treatments have been
      included in the same study. A new classification of patients based on hormonal
      sensitivity is proposed to recognize that androgen-independent proliferation,
      progression of disease despite castrate levels of testosterone, does not
      necessarily mean that a tumor is refractory to hormonal manipulations. Future
      trials in hormonally relapsed patients must include more details of the hormonal
      therapies utilized.

PMID- 7624984
TI  - Partial nephrectomy for renal cell carcinoma.

PMID- 7624985
TI  - Radical nephrectomy.

PMID- 7624986
TI  - Intrarenal satellites of renal cell carcinoma: histopathologic manifestation and
      clinical implication.
AB  - OBJECTIVES: This study was designed to gain more insight into the incidence of
      satellites of renal cell carcinoma related to the pathologic stage and grade of
      the primary tumor. METHODS: One hundred eight nephrectomized kidneys with renal
      cell carcinoma were sectioned at 3-mm intervals and inspected microscopically for
      satellite carcinomas. The number, site, size, and distance of satellite
      carcinomas found were recorded in relation to the primary carcinoma. RESULTS: The
      overall incidence of satellite carcinoma was 6.5% (7 of 108). The incidence of
      satellite carcinoma in relation to the pathologic staging of the primary tumor
      was 7.1% (1 of 14) in pT1, 3.0% (2 of 66) in pT2, and 14.3% (4 of 28) in pT3. The
      incidence was higher in patients with N1 disease (25%) than in those with NO
      (5.0%), and higher in M1 disease (25%) than in those in MO (5.77%). There was no
      relationship between the grade and multicentricity. CONCLUSIONS: The incidence of
      satellite carcinoma was higher in cases with high-stage primary carcinoma.
      However, even in localized diseases (PT1, pT2), satellite carcinomas were found
      at at 3.75% incidence. When nephron-sparing surgery is indicated in low-stage
      cases, precise clinical staging using a combination of various imaging modalities
      is mandatory, with intraoperative ultrasonography being one possible modality for
      detecting a concomitant satellite carcinoma.

PMID- 7624988
TI  - Efficacy of a new endoureterotomy balloon for the treatment of benign ureteral
      strictures using the porcine model.
AB  - OBJECTIVES: Endoureterotomy and balloon dilation are techniques that have shown
      promise as treatment modalities for benign ureteral stricture disease. In this
      animal investigation, the results of a new endoureterotomy balloon that
      simultaneously incises and dilates the ureteral stricture via a retrograde
      approach are discussed. METHODS: Using the female pig model, 9 subjects with
      benign ureteral strictures were treated: 7 with the endoureterotomy balloon and 2
      with balloon dilation only. RESULTS: Success based on radiologic parameters and
      Whitaker testing was obtained in 5 of the 7 animals treated by endoureterotomy.
      In both animals treated by balloon dilation only, recurrent ureteral stricture
      disease developed. CONCLUSIONS: This preliminary investigation suggests that this
      new device may be an effective treatment for benign ureteral stricture disease
      and that the further study in clinical trials is warranted.

PMID- 7624987
TI  - Antimicrobial prophylaxis in management of urinary tract stones by extracorporeal
      shock-wave lithotripsy: is it necessary?
AB  - OBJECTIVES: In a prospective randomized study, we evaluated the incidence of
      urinary tract infections following extracorporeal shock-wave lithotripsy (ESWL)
      and the necessity of prophylactic antibiotic administration in patients treated
      with this modality. METHODS: A total of 360 consecutive patients with renal and
      ureteric stones who had sterile urine before ESWL treatment and did not have any
      increased risk of infection received either a single dose of 400 mg of ofloxacin
      or no prophylaxis. Patients were followed by simple urine analysis and urine
      cultures together, with clinical evaluations. RESULTS: Only 3 patients (0.8%) had
      positive urine cultures at 1 week after ESWL. Two of these patients were in the
      antibiotic prophylaxis group. CONCLUSIONS: The incidence of urinary tract
      infections after ESWL is extremely low, provided that patients have sterile urine
      before ESWL, and prophylactic antibiotics are not required.

PMID- 7624989
TI  - Detection of bladder tumors by immunostaining of the Lewis X antigen in cells
      from voided urine.
AB  - OBJECTIVES: A study was made to determine the sensitivity and specificity of
      immunostaining of the Lewis X antigen in exfoliated urothelial cells from voided
      urine, for the detection and surveillance of bladder tumors. METHODS: Three
      consecutive voided urine specimens were obtained from 101 patients, 78 of whom
      were under surveillance because of a history of bladder tumors, and 23 were being
      evaluated because of hematuria or irritative urinary symptoms. Indirect
      immunoperoxidase staining of two urine samples was done on cytocentrifuge slides,
      using the P12 monoclonal antibody against the Lewis X antigen. The diagnosis of
      the presence of urothelial tumor was made if more than 5% of the cells showed a
      typical red-brown staining. Cytopathologic examination of the third urine
      specimen was done according to Papanicolaou. Each patient underwent cystoscopy,
      and biopsies were obtained whenever there was endoscopic evidence of bladder
      tumors or carcinoma in situ. RESULTS: Cystoscopy and biopsies revealed
      transitional cell carcinoma in 32 patients, whereas 69 patients had no evidence
      of bladder tumors. Immunocytology of one urine sample showed true-positive
      results in 26 of the 32 patients with bladder tumors, corresponding to a
      sensitivity of 81.25%. When two samples were examined, a sensitivity of 97% and a
      specificity of 85.5% were obtained. When the results of cytology and
      immunocytology were combined, sensitivity reached 100%. High-grade and low-grade
      transitional cell tumors were detected with equal efficiency. CONCLUSIONS: The
      use of P12 monoclonal antibody for evaluation of Lewis X reactivity in cytologic
      preparations from multiple voided urine specimens can improve the sensitivity of
      noninvasive detection of bladder cancer. The technique may ultimately replace
      cystoscopy in monitoring therapeutic response and tumor recurrence.

PMID- 7624990
TI  - Prostate capsule: computerized morphometric analysis of its components.
AB  - OBJECTIVES: There is little objective information on what is designated as being
      the prostate capsule. We have quantified objectively with computerized image
      analysis the percentage of smooth muscle fibers (SMFs) surrounding the surgical
      specimens of radical prostatectomies. METHODS: Ten radical prostatectomy
      specimens were used. Six different parts from prostate lobe were analyzed. Thirty
      different fields were examined from each tissue section. For tissue sections,
      different stains were used: hematoxylin and eosin, Masson's trichrome, and
      immunohistochemical staining with antiactin for SMFs. RESULTS: The mean thickness
      of the prostate capsule was 0.5 to 2 mm. The mean percentages of SMFs in the
      different regions of the prostate capsule was 30.6%. No difference was noted
      between the percentage of SMFs in the prostatic capsule compared with that in the
      prostate parenchyma itself (30.7%). CONCLUSIONS: This study provides objective
      evidence to demonstrate that the prostate does not have a true capsule. This
      capsule represents a fibromuscular band that probably should be considered as the
      extension of the internal parenchyma.

PMID- 7624991
TI  - Goserelin versus orchiectomy in the treatment of advanced prostate cancer: final
      results of a randomized trial. Zoladex Prostate Study Group.
AB  - OBJECTIVES: To compare the efficacy and safety of goserelin and orchiectomy in
      patients with stage D2 prostate cancer. METHODS: A randomized, open, multicenter
      study was conducted in 283 patients. Patients were allocated to goserelin, 3.6 mg
      every 28 days or to orchiectomy. Study end points were endocrine response,
      objective response, time to treatment failure, survival, and tolerability.
      Objective response was based on modified criteria of the National Prostate Cancer
      Project. RESULTS: Serum testosterone decreased from baseline to castrate levels
      by week 4 in each group and remained below castrate levels thereafter. Acid
      phosphatase and alkaline phosphatase concentrations also decreased in each group.
      The goserelin and orchiectomy groups had similar results for objective response
      (82% versus 77%) and had similar medial times to treatment failure (52 versus 53
      weeks) and survival (119 versus 136 weeks). No significant interactions between
      treatments and prognostic factors were observed. Adjusting for baseline
      testosterone concentration had no effect on survival outcome. Race had no
      influence on outcome or efficacy end points. Common adverse events in both groups
      were pain, hot flushes, and lower urinary tract symptoms. CONCLUSIONS: Goserelin
      is well tolerated and as effective as orchiectomy in patients with Stage D2
      prostate cancer.

PMID- 7624992
TI  - Elevated 12-lipoxygenase mRNA expression correlates with advanced stage and poor
      differentiation of human prostate cancer.
AB  - OBJECTIVES: Prostate cancer is the most frequently diagnosed cancer and the
      second leading cause of cancer death in males in the United States. The mortality
      is due mainly to distant metastasis. Therefore, predicting the prognosis of
      prostate cancer patients is an important clinical problem. Previously, we
      demonstrated that a 12-lipoxygenase (12-LOX) metabolite of arachidonic acid,
      12(S)-hydroxyeicosatetraenoic acid, enhances the invasiveness of prostate cancer
      cells and that a 12-LOX-selective inhibitor [N-benzyl-N-hydroxy-5
      phenylpentanamide] reduces experimental metastasis in animal model systems. In
      this study, we investigated the potential of 12-LOX as a predictor for the
      aggressiveness of prostate cancer. METHODS: The mRNA expression level of 12-LOX
      in 122 matching prostate normal and cancerous tissues were measured by
      quantitative reverse transcription- polymerase chain reaction. Possible
      association between 12-LOX expression and histologic grade, pathologic and
      clinical stage, margin positivity, age, and race was analyzed. RESULTS: 12-LOX
      mRNA levels were elevated in cancer cells and the expression associated with poor
      differentiation and invasiveness of prostate cancer. Overall, 46 (38%) of 122
      evaluable patients showed elevated levels of 12-LOX mRNA in prostate cancer
      tissues compared with the matching normal tissues. A statistically significantly
      greater number of cases were found to have an elevated level of 12-LOX among T3,
      high grade, and surgical margin-positive than T2, intermediate, and low grade,
      and surgical margin-negative prostatic adenocarcinomas. CONCLUSIONS: Our data
      suggest that elevation of 12-LOX mRNA expression occurs more frequently in
      advanced stage, high-grade prostate cancer and that 12-LOX may serve as an
      indicator for progression and prognosis of prostate cancer. This enzyme also may
      be a novel target for the development of anti-invasive and antimetastatic agents.

PMID- 7624993
TI  - Micropuncture retrieval of epididymal sperm with in vitro fertilization:
      importance of in vitro micromanipulation techniques.
AB  - OBJECTIVES: To evaluate the importance of in vitro micromanipulation techniques,
      specifically intracytoplasmic sperm injection (ICSI), for the fertility treatment
      of men with congenital absence of the vas deferens (CAV) or other
      unreconstructable male reproductive tract obstruction. METHODS: Results using
      ICSI during in vitro fertilization (IVF) were compared to previously published
      results of IVF alone and IVF with other micromanipulation techniques at the same
      infertility center. Main outcome parameters evaluated were: fertilization rate
      per oocyte, clinical pregnancy rate, and ongoing pregnancies and deliveries.
      RESULTS: IVF with ICSI yielded a fertilization rate per oocyte of 140 of 312
      (45%) and a clinical pregnancy rate of 14 of 27 (52%) per cycle of sperm and egg
      retrieval. Ongoing pregnancies or deliveries have occurred for 13 of 27 (48%)
      cycles with ICSI. These results were better than our previously published results
      of IVF alone or in conjunction with the micromanipulation techniques of subzonal
      insertion (SuZI) or partial zona dissection (PZD) that yielded a 119 of 631 (19%;
      P < 0.0001) fertilization rate, clinical pregnancy rate of 14 of 51 (27%; P <
      0.001) and ongoing pregnancy or delivery for 12 of 51 cycles (24%; P < 0.001).
      CONCLUSIONS: Epididymal sperm retrieval should be performed only when
      micromanipulation is available in conjunction with IVF to maximize chances of
      fertilization and subsequent pregnancies. The use of ICSI for epididymal sperm
      appears to maximize chances of pregnancy for couples with surgically
      unreconstructable obstructive male infertility.

PMID- 7624994
TI  - New laparoscopic suturing device: initial clinical experience.
AB  - OBJECTIVES: New instrumentation and techniques have enabled laparoscopic surgeons
      to perform complicated reconstructive procedures. Few centers have attempted
      these procedures because of the excessive time involved with laparoscopic
      suturing. The Endo stitch suture device was developed to facilitate suture
      placement. We clinically compared conventional intracorporeal suturing and Endo
      Stitch suturing for laparoscopic suture placement and knot tying. METHODS:
      Intracorporeal suturing was used to complete laparoscopic dismembered
      pyeloplasties and bladder neck suspensions. Sutures were placed with either
      needle holders and graspers or the automatic suture device. A total of 85
      maneuvers were assessed. Operative videotapes were reviewed to assess accuracy of
      suture placement, knot tying, and time to place suture and tie knots. All
      suturing was performed by an experienced laparoscopist. RESULTS: Accuracy of
      stitch placement and knot tying were equivalent. The average time for stitch
      placement with the Endo Stitch was 43 +/- 27 seconds (n = 41). This was
      significantly less than the average stitch placement time for conventional
      suturing, which was 151 +/- 24 seconds (n = 14). The Endo Stitch knot tying was
      completed in an average of 74 +/- 50 seconds (n = 17), whereas knot tying with
      the conventional technique took 197 +/- 70 seconds (n = 13). The needle is
      automatically loaded in the Endo Stitch after each suture and is immediately
      ready. CONCLUSIONS: The Endo Stitch device reduced the amount of time needed for
      placement of stitches and knot tying. Reconstructive laparoscopic procedures
      requiring multiple suture placement may be completed in a shorter time period
      using this instrument.

PMID- 7624995
TI  - Recurrent Staphylococcus aureus renal abscess in a child positive for the human
      immunodeficiency virus.
AB  - A 10-year-old girl with the human immunodeficiency virus was found to have a
      Staphylococcus aureus renal abscess with perinephric extension. The abscess was
      drained first percutaneously and then surgically, and the patient received a 6
      week course of intravenous antibiotics. Three months later, the abscess recurred,
      necessitating a nephrectomy. The extended morbidity and difficulty of eradicating
      S aureus suggest that, in immunocompromised patients, early aggressive surgical
      management is indicated.

PMID- 7624996
TI  - Intrapulmonary lymph nodes masquerading as renal cell carcinoma metastases.
AB  - Clinically apparent intrapulmonary lymph nodes are rare but may be incorrectly
      diagnosed as pulmonary metastatic disease. We report on a 65-year-old man who
      presented with a left renal mass and left lower lobe pulmonary nodules that were
      interpreted radiographically to be consistent with metastatic disease. Surgical
      pathologic examination confirmed intrapulmonary lymph nodes and a Stage II renal
      cell carcinoma. Failure to diagnose intrapulmonary lymph nodes may result in
      erroneous diagnosis of metastatic disease and preclude potentially curative
      treatment.

PMID- 7624997
TI  - Transitional cell carcinoma in a duplicated ectopic ureter.
AB  - We report a case of transitional cell carcinoma occurring within an ectopically
      located upper pole ureter of a completely duplicated collecting system in an 81
      year-old man. Presentation, evaluation, and management issues are discussed.

PMID- 7624998
TI  - Combined abdominal and posterior sagittal transrectal approach for the repair of
      rectourinary fistula resulting from a shotgun wound.
AB  - The repair of rectourinary fistulas is frequently a matter of great difficulty.
      We report the case of a young man who sustained a shotgun wound to his pelvis and
      developed a fistula from the bladder neck to the rectum, which was repaired by a
      combined transabdominal and posterior sagittal transrectal approach. We recommend
      that this procedure should be part of the surgical armamentarium available to
      deal with such complicated lesions.

PMID- 7624999
TI  - Laparoscopic pyeloplasty for secondary ureteropelvic junction obstruction:
      preliminary experience.
AB  - OBJECTIVES: To identify whether laparoscopic pyeloplasty is a reasonable
      treatment option for secondary ureteropelvic junction (UPJ) obstruction. METHODS:
      Since March 1994, we have performed laparoscopic pyeloplasties for secondary UPJ
      obstruction on 4 symptomatic patients ranging in age from 26 to 39 years. Prior
      failed procedures included antegrade endopyelotomies (3) and acucise
      endopyelotomies (3). Two patients underwent two prior endopyelotomies. Techniques
      of laparoscopic reconstruction included Anderson-Hines dismembered (3) and Culp
      Deweerd flap (1) procedures. Repairs were performed with interrupted and running
      3.0 and 4.0 Vicryl sutures using intra-corporeal knots and Lapra-Ty absorbable
      suture clips. RESULTS: Average operating time was 530 minutes (range, 465 to
      645), which included preoperative cystoscopic placement of an external 7 F
      occlusion balloon catheter into the renal pelvis and placement of an internal
      double pigtail ureteral stent at the conclusion of the procedure. Average blood
      loss was 111 cc (range, 75 to 150). All 4 patients were found to have anterior
      crossing vessels intraoperatively. Average postoperative hospital stay was 4 days
      (range, 3 to 7). All 4 patients have a patent, nonobstructed UPJ by either
      Whitaker test or diuretic renography at an average of 3.3 months postoperatively
      (range, 1 to 5). Average return to normal activity was 4.5 weeks (range, 3 to 8).
      Utilizing an analogue pain scale, 2 of the patients are pain-free, and the other
      2 are improved (45% and 85%) at an average of 8 months (range, 2 to 12)
      postoperatively. One patient developed stones in the renal pelvis and required
      percutaneous nephrolithotomy 10 weeks postoperatively. CONCLUSIONS: Laparoscopic
      pyeloplasty appears to be feasible and effective, although a technically
      challenging operative procedure for treating secondary (postendopyelotomy) UPJ
      obstruction. Further clinical experience and long-term follow-up are needed.

PMID- 7625000
TI  - Laser tissue soldering in urinary tract reconstruction: first human experience.
AB  - OBJECTIVES: Laser tissue soldering (LTS) in the urinary tract provides an
      immediate leak-free seal and may avoid complications seen with conventional
      repair (such as fistula and stricture). We have begun a Phase I clinical trial
      investigating the use of LTS in performing urologic reconstructive surgery.
      METHODS: Ten patients (aged 3 months to 38 years) underwent urologic
      reconstruction using LTS with a protein solder composed of human albumin (42%)
      and indocyanine green dye. In each case standard microsuture repair preceded
      laser-soldered suture line reinforcement. Anastomotic closure time and immediate
      leak pressure were measured. Postoperatively, all patients were evaluated for
      evidence of complications, including stricture, fistula formation, or impaired
      healing. RESULTS: Using LTS as an adjunct to suturing added an average of 7.9 +/-
      3.0 minutes (28%) to the overall mean anastomotic time of 28.3 +/- 9.4 minutes.
      Intraoperative leak pressure measurements for laser-soldered anastomoses (> or =
      94.2 +/- 24.2 mm Hg) were significantly higher (P < 0.001) than primarily sutured
      anastomoses (20 +/- 2.9 mm Hg). Two instances of suture disruption (20%) occurred
      during laser activation, neither of which were repaired with sutures. Average
      follow-up for all patients was 7.1 + - 2.2 months. There were no intraoperative
      or postoperative complications, including the 2 patients with suture disruption.
      CONCLUSIONS: These initial clinical results indicate that LTS is safe, easy to
      perform, and, contrary to conventional suturing, provides an immediate leak-free
      closure. Follow-up in these and other patients, as well as those undergoing
      sutureless and stent-free procedures, will determine whether our method of LTS
      benefits patients undergoing urologic reconstruction.

PMID- 7625001
TI  - Current concepts in the pathophysiology of testicular undescent.
AB  - At present, we believe that descent of the testes within the human is a complex
      event mediated by both hormonal and mechanical factors. We hypothesize that
      descent of the testes occurs as a result of the secretion of an androgen
      independent factor from a normal testis (descendin). This paracrine factor is
      responsible for the rapid proliferation (outgrowth) of the ipsilateral
      gubernaculum. The development of the gubernaculum results in creating a dilated
      inguinal canal, the width of which matches the testicular width. Descent of the
      testes through the inguinal canal is an interplay between abdominal pressure, a
      patent processus vaginalis, and androgen-induced gubernacular regression. We
      hypothesize that androgens (under control of an intact hypothalamic pituitary
      axis) alter the viscoelastic properties of the gubernaculum, reducing the
      turgidity of the gubernaculum and allowing intra-abdominal pressure to push the
      testis into the scrotum. Cryptorchidism can therefore result when any one or more
      of the involved factors malfunction.

PMID- 7625002
TI  - [The diagnosis and surgical treatment of metastatic liver tumors].
AB  - The authors have carried out 48 resections of liver for it's metastatic injure.
      The most frequent source of metastatic spread in liver occurred to be colorectal
      cancer. Right liver lobe was found to be injured by the metastatic tumour more
      often. After liver resections of various value the frequency of complications was
      37.5%, postoperative lethality--2.1%. Presented data evidence the necessity of
      widening recommendations to perform radical operative interventions in patients
      with solitary and single metastases in liver.

PMID- 7625003
TI  - [The clinical picture and diagnosis of postoperative intra-abdominal
      hemorrhages].

PMID- 7625004
TI  - [The surgical treatment of false aneurysms of the distal anastomoses after
      aortofemoral reconstructions].

PMID- 7625005
TI  - [The characteristics of and preventive measures for injuries to the major vessels
      by the pins during transosseous extrafocal osteosynthesis].

PMID- 7625006
TI  - [Combined heparinization during hemosorption].

PMID- 7625007
TI  - [A method for measuring blood viscosity at low rates of displacement].

PMID- 7625008
TI  - [Valveless trocars for the LVS-1 laparoscope].

PMID- 7625009
TI  - [A method for gastric resection].

PMID- 7625010
TI  - [A new method of forming a biliodigestive anastomosis].

PMID- 7625011
TI  - [A fixator for transduodenal papillosphincterotomy].

PMID- 7625012
TI  - [An optimal variant in forming a terminal anastomosis in resection of the
      sigmoid].

PMID- 7625014
TI  - [100 implants of the Planiks disk artificial heart valve].

PMID- 7625013
TI  - [The effect of one-time antibiotic prophylaxis on the course of the postoperative
      period in surgical patients].

PMID- 7625015
TI  - [Laparoscopy in hemoperitoneum].

PMID- 7625016
TI  - [Peritonitis as a complication of acute destructive cholecystitis].

PMID- 7625017
TI  - [An analysis of mortality in acute cholecystitis].

PMID- 7625018
TI  - [The current treatment of femoral hernias].

PMID- 7625019
TI  - [Defects of the anterior abdominal wall in the newborn (a review of the foreign
      literature)].

PMID- 7625020
TI  - [How to avoid nerve damage during the implantation of pacemakers into the
      axillary area].

PMID- 7625021
TI  - [Thymogen immunocorrection in the surgical treatment of complicated forms of
      cholelithiasis].
AB  - On the basis of experimental and clinical investigations the authors showed
      immunity depression in complicated forms of cholelithiasis. Thymogene appeared to
      be efficient for immunocorrection that permitted to lower the frequency of
      postoperative complications and lethality.

PMID- 7625022
TI  - [The immediate and late results of a gastropancreatoduodenal resection].
AB  - The results of gastropancreatoduodenal resection (GPDR) in 111 patients have been
      analysed. It is indicated that GPDR application in the presence of recommendation
      and technical possibility of performing in oncological patients is reasonable.
      This operation should be carried out in specialized institutions, where early
      diagnosis and exact identification of biliopancreatoduodenal zone injury
      character are possible, as well as qualitative preoperative preparation and
      intensive therapy during the operation and in early postoperative period.

PMID- 7625024
TI  - [The surgical treatment of catheter-related cardiac and vascular embolisms].
AB  - Basing on the experience of the surgical treatment of 15 patients with catheteric
      embolism of the heart and vessels the authors concluded that septic occurrence in
      given patient category requires urgent operative intervention. In catheteric
      heart embolism in patients with heart defects surgical interventions may be
      performed in nonperfusing deep (28-25 degrees C) hypothermal protection,
      permitting simultaneous removal of heart foreign body and to correlate heart
      defects not requiring continuous circulation control.

PMID- 7625023
TI  - [The factors promoting dystrophic pathology of the hand and duodenal peptic ulcer
      in women].
AB  - The authors have made an attempt to make exact the reasons of the frequent
      association of hand dystrophic pathology and duodenal ulceration disease in
      women. It is revealed that pointed diseases are to be the late symptoms of
      equally directed alterations in the organism, including neuro-humoral and immune
      mechanisms of adaptation, occurring in women even in sexual maturing period and
      being the favourable background for occurrence of various diseases including hand
      dystrophic pathology and duodenal ulcerative disease.

PMID- 7625025
TI  - [Lavage of the infected peritoneal cavity using agarose-based immunoaffinity gel
      sorbents].
AB  - In the paper antistaphylococcus and polymixine liquid sorbents are used to lavage
      infected rat abdominal cavity against gram-positive and gram-negative microfloral
      toxins. Sorbents have been revealed to remove erythrocyte antigens from the
      surface, that are affine to immobilized ligands on the matrix. Polymyxine affine
      sorbent arises quality of the usual lavage of the infected abdomen. 3 hour lavage
      by fresh portions of the affine sorbent removes fixed toxins from the abdominal
      surface. Sorbent injection into purulent abdomen for 24 hours provides blood
      detoxication.

PMID- 7625026
TI  - [The possibilities for correcting hydro ion metabolism in acute surgical
      pathology in diabetics].
AB  - On the basis of examination of 634 patients with acute surgical endotoxemia in
      patients with diabetes mellitus the following features have been revealed:
      hypertonic dehydration has dominant as well as hyperkalemia, marked
      hyperazotemia. Oliguria was detected only in 18.8% of patients. Plasmic
      osmolarity was 296-348 mosm/l, predominantly for account of hyperazotemia and
      hyperglycemia. 86.97% of patients showed ketoacidosis. The scheme of intensive
      therapy of surgical endotoxemia in patients with decompensative diabetes mellitus
      with programme applications for paternal computers is suggested.

PMID- 7625027
TI  - [Physiotherapeutic methods in the combined treatment of patients with lactation
      mastitis].
AB  - Physiotherapeutic methods of therapy were used in complex treatment of 839 from
      1435 patients with lactic mastitis diadynamic currents, high frequent ultrasound,
      ultraviolet irradiation of the wounds, UHF, local oxygen therapy of the wounds
      combined with UVI. Comparative data of the results of the treatment methods
      evidence that the most efficient in local treatment are to be ultrasound and
      oxygen therapy of the mammary glands combined with ultraviolet irradiation.

PMID- 7625028
TI  - [The treatment of posttraumatic and true arterial aneurysms of the extremities].
AB  - The work presents an analysis of the nearest results of treatment of 82 patients
      with pulsating hematomas, false and true aneurysms of the upper and lower
      extremity vessels depending on the kond of the pulsating formation, variants of
      complications in the course of disease, the level and size of defects of the
      vessel as well as of the state of the distal bed. Most optimum operations are
      those with using autovenous transplants, patients with false aneurysms excluded.
      In all the operated patients the adequate blood circulation was restored and the
      extremity was saved.

PMID- 7625029
TI  - [Giant-cell tumors of the bones: experience with resections and adjuvant
      cryotherapy].
AB  - On the basis of surgical treatment of 45 patients with giant-cell bone tumor (in
      28--associated with cryotherapy) the role of cryogenic method of treating of
      patients with giant-cell tumor is shown. Efficiency of cryodestruction of remnaut
      bone cavities as well as it's preponderance in comparison with common
      (traditional) methods of treating is stated.

PMID- 7625030
TI  - [An ectopic chorionepithelioma in a man].

PMID- 7625031
TI  - [The choice of the hemostatic method in profuse ulcerative hemorrhages in middle
      aged and elderly patients].

PMID- 7625032
TI  - [A gastrocolonic fistula developing after gastric resection for complicated
      pyloroduodenal ulcer].

PMID- 7625033
TI  - [An extensive rupture of the duodenum].

PMID- 7625034
TI  - [The successful treatment of a female patient with a stomach polyp causing
      duodenal obstruction, acute pancreatitis and mechanical jaundice].

PMID- 7625035
TI  - [Echinococcosis of the head of the pancreas].

PMID- 7625036
TI  - [The surgical treatment of rectal strictures].

PMID- 7625037
TI  - [Adamantinoma of the radius].

PMID- 7625038
TI  - [The morphostructural disorders of the gastric mucosa in peptic ulcer].
AB  - 200 patients with ulcerative disease of the stomach have been examined. It is
      indicated that 87% of patients showed chronic gastritis, more often with mucosal
      atrophy. 7.9% of patients revealed isolated dysplasia of various expression
      degree, in 38.2%--isolated regenerative disturbances, and in 24.3%--associations
      of dysplasia with regeneration defects. 9.5% of patients showed malignant ulcer
      (with atrophic and atrophic hyperplastic gastritis--in 13.8% of cases, and with
      isolated dysplasia--in 41.7%, with isolated regenerative disturbances--in 5.2%,
      with association of dysplasia and regenerative defects--in 29.7%). To determine
      resection value one should account extensions morpho-structural alterations in
      gastric mucosal membrane.

PMID- 7625039
TI  - [A system of individual immunotherapy for intracranial complications and the
      local immune reactions of the cerebrospinal fluid].
AB  - The influence of the individual immunotherapy with the selection of the
      immunomodulator upon the level of lymphocyte functional activity on sanogenetic
      mechanisms of local immune system of the cerebrospinal liquid was investigated.
      It is shown, that sanogenetic potential of the CSF local immune system is
      mediated by the presence of sufficient adaptive resources, maintaining protective
      immunobiochemical processes in the active state for the whole period of
      adaptation to injury. Individual immunotherapy promotes optimization of the
      sanogenetic mechanisms in the cerebral local immunity system on postoperative
      period in complicated craniocerebral injury.

PMID- 7625040
TI  - [Immunological reactivity and nonspecific resistance in the early posttraumatic
      period in victims with closed craniocerebral trauma].
AB  - The data of clinical neuroimmunology permit to separate some immunological
      syndromes in the course and in the outcome of the injured brain disease. In
      cerebral concussion these are to be a stressing immune deficiency and reversible
      neurosensibilization; lightly grave contusions is followed by the syndrome of
      immunobarrier function disturbance; in moderately grave or grave contusions-
      border-line immunodysfunction; the dead showed unfolding of the neurogenic
      immunodysfunction syndrome, worsened by immunologic paralysis.

PMID- 7625041
TI  - [The role of middle-molecule peptides in the pathogenesis of traumatic disease].
AB  - On the basis of study of mass-spectrum of blood plasma ultrafiltrate in 21
      injures with severe associated trauma during first four posttraumatic days and in
      healthy persons one can suggest that combinations with molecular weights of 300
      1050 Da are to be one of the important regulatory mechanisms of posttraumatic
      adaptative processes. With increasing of the injury gravity reorientation of the
      levels of adaptative reactions management and level enhancing of mediomolecular
      regulators are found to be occurred.

PMID- 7625042
TI  - [Necrotic pseudarthroses].

PMID- 7625043
TI  - [The successful treatment of a victim with lacerated stab wounds to 3 anatomical
      areas].

PMID- 7625044
TI  - [Enteroplasty in the treatment of duodenal trauma complicated by peritonitis].

PMID- 7625045
TI  - [The use of spatial image filtration in the diagnosis of tumors and tumor-like
      processes of the jaws in children].
AB  - 34 children were examined for tumours and tumor-like jaws diseases odontomas,
      giant cell tumours, fibrous osteodysplasias, epulides, eosinophilic granulomas.
      Roentgenograms and tomograms of the patients have undergone space filtration on
      the device for the DAR-2 roentgenogram analysis with separation of the upper and
      middle space frequencies of the picture. Space filtration separated features of
      the picture having differentially diagnostic meaning and characterizing the
      particularities of the tumour structure, it's bone border, alteration of the
      surrounding soft tissues.

PMID- 7625046
TI  - [The surgical treatment of injuries to the deep branch of the radial nerve in
      children].
AB  - On the basis of examination and treatment of II children the authors showed that
      the injury of the deep branch of children radial nerve sometimes is connected
      with operative interventions, performing for fractures and fracturodispositions
      of the radial bone in the elbow joint area, and in part of children-in forearm
      soft tissue wounds. Reconstruction of the deep branch with the help of
      autotransplants performed during the first year after injury results in the high
      recovery rate of reduction of the I-V finger extension.

PMID- 7625047
TI  - [The "edematous scrotum syndrome" in children].

PMID- 7625048
TI  - [The stimulation of reparative regeneration with demineralized bone matrix in
      puncture osteoplasty operations for bone cysts in children].
AB  - The authors present the data on positive influence of demineralized osteomatrix
      (DOM) on the osteogenesis in the experimental conditions. On the basis of data
      received the method of puncture osteoplastic operation with DOM application was
      developed. Puncture method was applied in 38 children. In 6 months 31 children
      cyst were liquidated, osteoarchitectonics was reduced, in 7 children rough
      trabecular picture remains.

PMID- 7625049
TI  - [The diagnosis and treatment of dislocation of the bones of both forearms with
      avulsion of both epicondyles in children].

PMID- 7625050
TI  - [Pathological dislocation of the femur in young children--a problem for the
      pediatrician, surgeon and orthopedist].
AB  - The authors consider, that orthopedic treatment should be carried out from the
      first days of illness together with the surgent of the unit of the newborns or
      the department of children surgery. The results of treatment of metaepiphysial
      osteomyelitis of femoral bone proximal end in early age children depend on timely
      diagnostics, treatment adequacy, rational fixation of the injured extremity and
      subsequent orthopedic treatment.

PMID- 7625051
TI  - [Calcinate of the abdominal cavity in a 12-year-old girl].

PMID- 7625052
TI  - [Acute alimentary duodenal obstruction].

PMID- 7625053
TI  - [Severe combined trauma to the liver with damage to the hepatic bile duct in a 6
      year-old child].

PMID- 7625054
TI  - [The surgical treatment of mandibular prognathism after the elimination of
      congenital clefts of the upper lip and palate].
AB  - In 4.47% of observation in patients after liquidation of the cleft lip and the
      palate the lower prognathia is diagnosed. From 77 patients being operated for
      lower prognathia such kind of patients were 7. The subsequence of the treatment
      measures is the following: correction of the upper jaw on the basis of
      compactostetomy and it's subsequent widening with orthodontic devices. In case of
      impossibility of sufficient widening of the dental arch the removable dental
      prosthesis is made for application on the upper jaw with doubling dental row
      accounting achievement of the desired bite. At the second stage the osteotomy of
      the upper jaw brunch and sagittal removement of the central section back are
      carried out up to achievement of the neutral bite. In dependence on jaw sagittal
      removement degree operative treatment may be performed by the intravial (I
      degree) or extravial method (II-III progemy degrees). Quite satisfactory remote
      results are presented. The paper is illustrated by 4 figures. The list of
      literature is given.

PMID- 7625055
TI  - [The replacement of resection defects of the bones by combined endoprostheses].
AB  - The authors possess the experience of 32 operations in patients with various
      pathology. In 74% being operated good functional results are received during
      observation period from 3 months to 4 years.

PMID- 7625056
TI  - An ultrasonographic study of bovine cystic ovarian disease and its treatment.
AB  - This study assessed the value of ultrasonography in characterising bovine cystic
      ovaries and monitoring their responses to different treatments. Thirteen cows
      were diagnosed by ultrasonography as having luteinised ovarian cysts and seven
      were diagnosed as having follicular ovarian cysts. Six of the former were treated
      with prostaglandin, four with a progesterone intravaginal device (PRID) and three
      with gonadotrophin-releasing hormone (Gn-RH); five of the latter were treated
      with Gn-RH and two with a PRID. All the animals were re-examined by ultrasound
      and blood was collected for the measurement of plasma progesterone concentration
      at intervals until oestrus. The treatment of the luteinised cysts with
      prostaglandin caused marked decreases in size and plasma progesterone
      concentration and altered their echotexture within two to four days; oestrus
      occurred within three to four days. In two of the cows treated with a PRID the
      cysts regressed within one to two weeks but the other two cows required
      supplementary treatment with prostaglandin; oestrus and ovulation were observed
      only after the cysts collapsed. Gn-RH stimulated oestrus and ovulation within
      three to four days but the cysts did not collapse until much later. The treatment
      of the follicular cysts with Gn-RH or a PRID caused fresh ovulation and the
      formation of a corpus luteum but had little immediate effect upon the cyst. The
      plasma progesterone concentrations in some of the cows with either follicular or
      luteal cysts were similar on the day of treatment and were therefore of little
      value in differentiating the types of cyst.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7625057
TI  - Anthelmintic resistance in nematode parasites of sheep: learning from the
      Australian experience.
AB  - In recent years the problem of anthelmintic resistance has become of major
      importance in sheep and goat flocks throughout the world. In Australia, concerted
      efforts were initiated in the mid 1980s to halt the increase in resistance by the
      development and promotion of regional worm control programmes. This article
      outlines the genesis of these programmes, the way in which they were promoted and
      successfully adopted by farmers, and the concerns for effective parasitic control
      of sheep and goat flocks in the future. The principles outlined should be
      applicable in other countries where anthelmintics are relied upon for the control
      of nematodes in livestock.

PMID- 7625058
TI  - Bovine tuberculosis in Swedish deer farms: epidemiological investigations and
      tracing using restriction fragment analysis.
AB  - Bovine tuberculosis was eradicated from Sweden after a programme lasting many
      years. By 1991, no tuberculosis in wildlife had been discovered for 50 years and
      the last case in cattle had occurred 13 years before. In 1991, the disease was
      identified in a herd of farmed fallow deer (Dama dama) and over the next three
      years nine other infected herds were identified. Investigation revealed that all
      the infected deer were either deer that had been imported into Sweden from the
      United Kingdom in 1987 or had been in contact with them. Restriction fragment
      analysis of eight isolates of Mycobacterium bovis from five of the herds showed
      that the isolates had identical patterns of DNA fragments, which indicated a
      common source of infection. Among more than 800 isolates of M bovis that have
      been analysed, these patterns were identical to those of only two previous
      isolates, both of which came from British deer. These results indicate that the
      eight Swedish strains of M bovis and the two British strains may have a common
      source of infection.

PMID- 7625060
TI  - Spontaneous otoacoustic emission in a pony.

PMID- 7625059
TI  - Spontaneous branchioblastoma in a koi carp (Cyprinus carpio).

PMID- 7625061
TI  - Testicular vascular hamartoma in a calf.

PMID- 7625063
TI  - New rules on medicines.

PMID- 7625062
TI  - Dearth of locums.

PMID- 7625064
TI  - New rules on medicines.

PMID- 7625065
TI  - Warble fly and sheep scab.

PMID- 7625066
TI  - Role of the OVS in the Meat Hygiene Service.

PMID- 7625067
TI  - Garden bird mortalities.

PMID- 7625068
TI  - Imports from third countries.

PMID- 7625069
TI  - Oestrogens in mares' urine.

PMID- 7625070
TI  - Blood transfusion in sickle cell disease.
AB  - Blood transfusion is used as a life-saving and prophylactic treatment in sickle
      cell disease. Despite the many complications associated with its use, few
      randomised controlled trials and careful research studies have been performed to
      fully define its role. This subjects is, therefore, discussed in the context of
      the current literature and authors' experience.

PMID- 7625071
TI  - Buffy-coat-derived platelet concentrates prepared from half-strength citrate CPD
      and CPD whole-blood units. Comparison between three additive solutions: in vitro
      studies.
AB  - The in vitro effects of storage of platelets prepared from 4 or 6 pooled buffy
      coat (BC) units and stored in a platelet storage medium consisting of 30-40% of
      CPD plasma or alternatively half-strength citrate CPD (0.5 CPD) plasma and 60-70%
      of different alternative platelet additive solutions (PASs) were evaluated.
      Measurements of mean platelet volume, pH, pO2, pCO2, bicarbonate, glucose,
      lactate, ATP, total adenine nucleotide content, extracellular lactate
      dehydrogenase or adenylate kinase activity, as markers for disintegration of
      platelets, and extracellular beta-thromboglobulin, as a marker for activation of
      platelets, were included in the in vitro studies. Previous studies indicated that
      a reduction of the citrate concentration from the standard 21 to 8 mmol/l is
      associated with a significant reduction of the consumption of glucose and
      production of lactate. Alternatively, similar effects can be obtained by the
      addition of acetate. In a preliminary paired study, the effects of different
      concentrations of acetate were tested. In an additional paired study, the effects
      of CPD plasma in combination with either saline or a PAS containing NaCl (115.5
      mmol/l), citrate (10 mmol/l), and acetate (30 mmol/l), pH 7.2 (PAS-2) were
      evaluated. 0.5CPD plasma in combination with either PAS-2 or a nonacetate PAS
      (PAS-1) were also tested. The storage of platelets in 0.5CPD plasma was used as a
      reference. The conclusions are: (1) A minimum acetate concentration of 30 mmol/l
      is needed to counteract the effects of citrate on the production of lactate. (2)
      pH and the bicarbonate buffering capacity are significantly better maintained in
      PAS-2 than in PAS-1.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7625072
TI  - Storage of platelet concentrates from overnight-stored blood and overnight-stored
      buffy coat: in vitro studies.
AB  - Platelet concentrates (PCs) were prepared from single buffy coats derived from
      fresh blood and from blood units stored overnight, as well as from buffy coats
      that were stored overnight. The platelet yield from overnight-stored buffy coats
      was similar to that of fresh blood or overnight-stored blood. PCs were stored at
      20-24 degrees C and on day 5 of storage, platelet aggregation with ADP was tested
      both at 37 and 25 degrees C. Stored platelets aggregated better at 25 degrees C
      than 37 degrees C. The maximal, aggregation (10 microM ADP) of stored platelets
      from overnight-stored buffy coats was 46 +/- 23% (n = 30), while that of stored
      platelets prepared either from fresh or overnight-stored blood was 27 +/- 21% (n
      = 29) and 22 +/- 15% (n = 29), respectively. Extracellular lactate dehydrogenase
      and ammonia levels, as well as elastase activity were similar in stored PCs of
      different origin. Our conclusion is that PCs prepared from overnight-stored buffy
      coat might also be suitable for storage and clinical use. In vivo studies are
      needed to confirm our findings.

PMID- 7625073
TI  - Establishment of a T-cell line from lymphocytes presumably implicated in
      posttransfusion graft-versus-host disease.
AB  - Posttransfusion graft-versus-host disease (PTGVHD) is known to develop in
      immunocompetent patients exhibiting clinical symptoms such as erythroderma,
      fever, liver dysfunction, diarrhea and pancytopenia. It is speculated that
      transfused blood donors' lymphocytes might recognize the recipients' HLAs as
      alloantigens. The thus stimulated lymphocytes might proliferate, expand and
      finally attack the host's immune system or tissues. However, details regarding
      these expanded donor cells such as: (1) whether they represent one clone or more,
      (2) the composition of lymphocyte subsets, and (3) the target HLA antigens of
      recipients, are not clear, since T-cell lines derived from PTGVHD patients have
      not yet been obtained. The aim of this study is to characterize T-cells
      responsible for PTGVHD and to identify their target molecules. For that purpose,
      we attempted to establish T-cell lines derived from a PTGVHD patient. We show
      that the established T-cell line, proven to be derived from donor lymphocytes,
      showed a CD4+ phenotype and had cytotoxic activities. Furthermore, we describe
      that the target of the cytotoxic T-cell line (CTL) is an HLA-DRB1*0405-related
      molecule of the patient.

PMID- 7625074
TI  - Prediction of the severity of haemolytic disease of the newborn. Quantitative IgG
      anti-D subclass determinations explain the correlation with functional assay
      results.
AB  - Sera containing anti-D, taken from 44 RhD-negative women with RhD-positive
      infants, were tested in antibody-dependent cellular cytotoxicity (ADCC) and
      monocyte monolayer assays (MMA) which used similar target and effector cell
      populations. In addition, the anti-D concentration was measured in the Auto
      Analyzer and the number of IgG1 and IgG3 anti-D molecules bound to the target red
      cells was measured by flow cytometry. The results of the functional assays and
      Auto Analyzer quantitation were examined for correlation with IgG subclass
      quantitation and all results were compared for their ability to predict the
      severity of haemolytic disease of the newborn (HDN). ADCC correctly predicted HDN
      in 39/44 (88.6%) cases, Auto Analyzer quantitation in 35/44 (79.5%) and the MMA
      in 32/44 (72.7%). For all three assays, the number of correct predictions was
      highest when the maternal serum contained both IgG1 and IgG3 anti-D. ADCC
      activity and HDN were correlated with the number of cell-bound IgG1 molecules (r
      > or = 0.58), but MMA activity was most closely correlated with the number of
      cell-bound IgG3 molecules (r = 0.68). Hence the superior predictive value of ADCC
      is due to its ability to reflect the IgG1 component of maternal anti-D, which has
      a better correlation than IgG3 anti-D with the severity of HDN.

PMID- 7625075
TI  - Evidence that the Gya, Hy and Joa antigens belong to the Dombrock blood group
      system.
AB  - Ten red cell samples lacking the high incidence Gya antigen were found to have
      the previously undescribed Do(a-b-) phenotype. Fifteen Hy- red cell samples were
      Do(a-b+) with weak expression of Dob and 6 Jo(a-) red cell samples were Do(a+)
      with weak expression of Doa. Five of the 6 Jo(a-) samples had extremely weak
      expression of Dob. The sixth Jo(a-) was Do(b-). Immune precipitates were prepared
      from radio-iodinated antigen-positive red cells with anti-Gya, -Hy, -Doa and Dob.
      Immunoblotting of these immune precipitates with affinity-purified anti-Gya and
      anti-Dob under non-reducing conditions revealed similar broadly migrating bands
      of M(r) 48,700-59,750, suggesting that the Doa and Dob antigens are carried on
      the same glycoprotein as Gya and Hy. The phenotypically associated high incidence
      Joa antigen has previously been shown to reside on the Gya/Hy glycoprotein.
      Enzyme-treated and chemically modified red cells tested with anti-Doa, -Dob, 
      Gya, -Hy and -Joa gave the same pattern of reactivity. We propose that Gya, Hy
      and Joa become part of the Dombrock blood group system and that, henceforth, the
      Gya/Hy-active glycoprotein be renamed the Dombrock-active glycoprotein. The Gy(a)
      Hy- Jo(a-) phenotype constitutes the 'null' phenotype within the Dombrock system.

PMID- 7625076
TI  - Expression of the erythrocyte antigen Henshaw (He; MNS6): serological and
      immunochemical studies.
AB  - Production of murine monoclonal antibodies to the low prevalence MNS antigen
      Henshaw (He; MNS6) has enabled more detailed study of this antigen. Using these
      directly hemagglutinating anti-He, red blood cells (RBCs) from 1695 people of
      African origin were screened in the USA and England. The prevalence of He+
      samples among these donors was 2.1%. In Natal, blood samples from 1218 black
      donors were screened with rabbit anti-He. The prevalence of He+ donors in this
      population was 7.0%. Immunoblotting confirmed that the He antigen is carried on
      an erythrocyte membrane component with a molecular mass that is indistinguishable
      from glycophorin B. Hemagglutination and immunoblotting demonstrated that ten of
      56 He+ samples tested more extensively had a reduced expression of the He
      antigen. The majority of He+ RBCs were S+; those He+ RBC samples that were S-s+
      more frequently had a weakened expression of He.

PMID- 7625077
TI  - A 'new' low-incidence red cell antigen, WARR: unique to Native Americans?
AB  - Investigation of a mild case of hemolytic disease of the newborn has led to
      recognition of a 'new' low-incidence red cell antigen, WARR (ISBT No. 700.55).
      Data gleaned from two kindreds, both with Native American heritage, exclude WARR
      from the MNS, Lutheran, Lewis, Duffy, Kidd, Xg, Chido/Rodgers, Kx and Gerbich
      blood group systems. Serologic or genetic evidence suggests it is not part of the
      Kell or Yt systems.

PMID- 7625078
TI  - Mixed-type auto-immune haemolytic anaemia in a patient with HIV infection.
AB  - A young HIV-infected patient presented with a severe auto-immune haemolytic
      anaemia with both warm and cold auto-antibodies, an infrequent category of anti
      erythrocyte auto-immunity. Serological findings were compatible with the presence
      of a low-titre, high-thermal-amplitude anti-I cold-reacting antibody and a pan
      reactive warm-reactive auto-antibody. Immunochemical characterisation of the warm
      antibody failed to identify any membrane protein acting as auto-antigen. This is,
      to our knowledge, the first reported case of mixed-type auto-immune haemolytic
      anaemia in a patient with HIV infection. Overt haemolysis is a very rare
      complication in HIV-infected patients, despite the high prevalence of a positive
      direct antiglobulin test reported in these patients. This suggests that HIV
      infection is a condition in which anti-erythrocyte auto-immunity is a serological
      finding without haemolytic effects in the large majority of cases.

PMID- 7625079
TI  - Haemolytic disease of the newborn due to anti-M.
AB  - A patient with haemolytic disease of the newborn (HDN) due to anti-M which
      required exchange transfusion is described. Anti-M antibodies are usually assumed
      to be naturally occurring and to consist of immunoglobulin M (IgM); many however
      have an immunoglobin G (IgG) component. In view of this and the described
      occurrence of HDN, recommendations are made regarding the management of a
      pregnancy in which anti-M antibodies are detected.

PMID- 7625081
TI  - A very simple and nonexpensive technique to prevent febrile nonhemolytic
      transfusion reactions in HLA-immunized patients.

PMID- 7625080
TI  - Effect of DEHP plasticizer on stored platelets.

PMID- 7625083
TI  - Proceedings of the 40th Scientific meeting of the Commonwealth Caribbean Medical
      Research Council. Barbados, April 27-29, 1995. Abstracts.

PMID- 7625082
TI  - Laparoscopic splenectomy in idiopathic thrombocytopenic purpura.

PMID- 7625084
TI  - [Days of Intensive Medicine-Transplantation. Wien, 2-4 February 1995. Abstracts].

PMID- 7625085
TI  - How did we manage to get to where we are? (and where are we going anyway...).

PMID- 7625086
TI  - SMS involvement in Marshfield brief 'most inappropriate'.

PMID- 7625087
TI  - Inflammatory pseudotumor of the bladder.

PMID- 7625088
TI  - Cervical cancer radiation injury to the urinary bladder and ureters: management
      by cecal augmentation to a previous ileal augmentation cystoplasty.
AB  - A case report of the management of severe post cervical carcinoma pelvic
      radiation injuries is presented. Management was accomplished by detubularized
      ileal augmentation cystoplasty followed by cecal augmentation to the
      detubularized ileal augmentation 4 years later when bilateral ureteral
      obstruction developed. The development of a vesicouterine fistula required the
      creation of a large bowel cecal conduit for cutaneous urinary diversion utilizing
      the cecal augmentation antireflux segment.

PMID- 7625089
TI  - Breast cancer screening complacency and compliance.
AB  - An HMO initiative designed to increase the compliance rate for the preventive
      service (mammography) is described. By looking at Security Health Plan charge
      data and sending a letter of notification when women are not up-to-date on their
      screening mammography, we were able to increase the mammography compliance rate
      from 47% to 72%. This system is designed to supplement the preferred method of
      recommendations by the primary care physician aided perhaps by a chart reminder
      system. Some problems with the methodology are described.

PMID- 7625090
TI  - Mid-course review: a progress report on the Healthier People in Wisconsin Year
      2000 Agenda.

PMID- 7625091
TI  - Practical considerations regarding ethical questions in the daily practice of
      medicine.

PMID- 7625093
TI  - [61st Annual meeting of the German Society of Cardiology-Heart and Circulatory
      Research. Mannheim, 20-22 April 1995. Abstracts].

PMID- 7625092
TI  - New column gives monthly look at WIPRO's quality improvement projects.

PMID- 7625094
TI  - [Prevention of reinfarction with 100 mg or 30 mg ASS daily?].
AB  - The prevention of heart infarction with 100 mg aspirin is common practice in
      Germany, in spite of the fact that it is based on only two small studies, the
      results of which are not generalized. Over 14 years, several experimental and
      clinical studies have shown that 20-30 mg aspirin/d for pharmacokinetic reason
      selectively inhibit the thromboxane synthesis while the endogenous prostacyclin
      synthesis remains intact. Prostacyclin plays an important cardioprotective role
      for the ischemic heart, having antiplatelet and antifibrillatory effects,
      potentiates the antiplatelet effect of the nitrovasodilators and nitric oxide,
      and increases the release of adenosine. A superior preventive action and lower
      side effects of 30 mg/d aspirin in direct comparison with higher doses was first
      proved by the Cottbus reinfarction study. The 30 mg aspirin tablet per day ought
      to replace the present prevention with higher doses.

PMID- 7625095
TI  - [Aspirin--yes, but 30 mg??].

PMID- 7625096
TI  - [Relation between plasma fibrinogen and the function of collateral coronary
      vessels].
AB  - The role of fibrinogen in LV function, especially after myocardial infarction, is
      still debated. We therefore investigated the relation between plasma fibrinogen,
      LV function and ischemic tolerance in 87 patients (average age 58.5 years) with
      proximal occlusion of the left anterior descending artery (LAD) and retrograde
      filling through noncompromised collaterals. Compared to a control group (n = 65;
      average age 57.0 years) study patients revealed significantly higher plasma
      fibrinogen levels (average 342.5 vs 316.1 mg/dl; p < 0.025) and a reduced
      ejection fraction (54.6 vs 75.5%; p < 0.0005). Study patients with collaterals
      were divided into three groups with increasing fibrinogen concentrations: Group I
      (n = 29) averaged 261 mg/dl (191-303), group II averaged 333.3 (304-362) and
      group III averaged 433.3 (364-742) (p < 0.0005). There were no significant
      differences regarding age, height, weight, number and age of previous infarctions
      and concomitant medical treatment; group III revealed a significantly higher
      proportion of women (21%) compared to group I (0%) (p < 0.005); group III also
      revealed significantly lower HDL-cholesterol and higher triglyceride levels
      compared to group I and group II, respectively (p < 0.05). Hematocrit, hemoglobin
      concentration, total and LDL-cholesterol showed no group differences. Group I
      with a low fibrinogen had the lowest endsystolic volume index (LVESVI) and
      highest ejection fraction (EF) (34.6 ml/m2 and 61.0%, respectively), whereas in
      patients of group II LVESVI amounted to 36.5 ml/m2 and EF to 57.3%, and in group
      III with the highest plasma fibrinogen levels LVESVI was 48.4 ml/m2 (group I, II
      vs III: p < 0.05) and EF 45.7% (group I, II vs III: p < 0.01). EF decreased
      exponentially with increasing fibrinogen concentrations (r = 0.5; p < 0.0005).
      Group III showed significantly higher LV enddiastolic pressures (19.1 mm Hg)
      compared to group I and II (14.6 and 14.4 mm Hg, respectively; p < 0.05). Fifteen
      patients in group I, 21 in group II, and 24 in group III showed akinetic LV wall
      segments (group I vs III: p < 0.0125). In addition, 21 patients in group I, 17 in
      group II, and only 10 in group III revealed exercise-induced myocardial ischemia
      (group I, II vs III; p < 0.05). In patients with ischemic ST-depression systolic
      rate pressure product (SRPP) at the onset of ischemic symptoms was 266.8 mm Hg x
      min-1 x 10(2) in group I, 246.8 in group II and 195.0 in group III (group I, II
      vs III; p < 0.005).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7625097
TI  - [Structural cardiac changes in patients with obstructive sleep apnea].
AB  - Important pathophysiological mechanisms in obstructive sleep apnea at night are
      increasing pleural pressure swings, hypoxia and hypercapnia, as well as central
      nervous arousals with consecutive fragmentation of regular sleep structure. They
      influence the cardiovascular system, at first only at night and at a later stage
      also during the day. This might result in cardiac structural changes: dilation
      and hypertrophy of the right ventricle, hypertrophy of the left ventricle,
      (especially of the muscular ventricular septum), dilation of right and left
      atrium. It is suggested that these cardiac structural changes are characteristic
      for obstructive sleep apnea and therefore define the "sleep apnea heart".

PMID- 7625098
TI  - [Experimental ultrasound angioplasty: in vitro resolution of thrombi].
AB  - A new ultrasonic angioplasty ablation catheter connected to a 19.5 kHz. 25 W
      transducer was tested in vitro for its ability to disrupt 12-h. 24-h, and 5-day
      old whole blood thrombi (n = 45.697 mg +/- 223 mg) and fibrin thrombi (n = 45.338
      mg +/- 133 mg), as well as 5-day-old cadaver thrombi (n = 8.270 mg +/- 71 mg)
      within 10 min. Five of each age were used as control thrombi in which the
      catheter was moved back and forth without ultrasound emission. The size of
      ablated thrombus particles was measured by a laser device. The power output at
      the end of the catheter was assessed calorimetrically. The loss of weight of
      whole blood thrombi was between 429 (74%) and 524 mg (91%) (p < 0.01, whole blood
      thrombi vs. control thrombi) and between 302 (85%) and 314 mg (95%) (p < 0.05)
      for fibrin thrombi, respectively. Thrombus age did not prove to be a highly
      significant influencing factor. The disruption rate for whole blood thrombi was
      0.75 to 1.05 mg/s and for fibrin thrombi 0.69 to 0.7 mg/s. It was only 0.09 mg/s
      for the cadaver thrombi. 93% of all particles ablated from whole blood thrombus
      ranged between 0-5 micron, less than 0.2% between 30-150 microns. For fibrin
      thrombi 69% of all particles were < 10 microns (25% between 10-20 microns). Only
      0.02% ranged between 300-600 microns, which was similar for cadaver thrombi. The
      mean measured power output at the catheter tip was 5.9 W compared to the power
      output of 25 W at the ultrasound generator.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7625099
TI  - [Crossing chronic coronary artery occlusions with a "laser wire" after failed
      attempted recanalization with other techniques].
AB  - The success rate of catheter recanalization of occluded coronary arteries is 50%
      to 80%. The reason for failure is frequently an occlusion which is to hard. As
      examples, two patients are reported with very hard coronary artery occlusions
      which were 5 months and 2 years old, respectively. There had been prior
      unsuccessful attempted treatment with other techniques. These occlusions could be
      recanalized with an 0.018 inch laser wire. Afterwards, a balloon dilatation could
      be carried out via the laser wire. The procedure was successful in both cases.

PMID- 7625100
TI  - [Imprints of coronary plaque particles in the PTCA balloon surface during the
      dilatation processing].
AB  - Seventy-six PTCA-balloons after coronary angioplasty were studied for superficial
      changes using scanning electron microscopy (SEM) after fixing in
      glutardialdehyde. Coronary plaque particles were identified on the balloon
      surface in 52 cases (68%). Twelve new and unused balloons were subjected to the
      same chemical treatment and SEM showed no imprints. The average length of the
      longest imprinted plaques was 128 +/- 201 microns and the average number of
      plaque particles per balloon was 4.9 +/- 2.7. The maximal dilatation pressure and
      the number of dilatations showed no influence on the impregnation of plaque
      particles. However, longer plaque imprints tended to occur under low dilatation
      pressure. Imprints of plaque particles were significantly higher in patients with
      low cholesterol (p = 0.0001) and low triglycerides (p = 0.0016). No correlation
      was seen between imprint length and lipid levels. Similarly, the different
      balloon materials (polyethylene, polyolefincopolymer) showed no significant
      differences with regard to plaque occurrence. The PTCA-balloons, plaque particles
      and six coronary plaques obtained after endatherectomy were subjected to energy
      dispersive x-ray analysis (EDX) under SEM as EDX reveals qualitative and
      quantitative information about the structural elements. Highly significant
      differences in calcium, sodium, phosphorus and silicon contents (p = 0.0000)
      between plaque particles and balloon surface were observed, owing to the absence
      of these in balloon material. Thus EDX offers additional advantages over SEM in
      that it clearly differentiates deformed balloon surface, plaque particle, and
      retained contrast medium. CONCLUSION: Plaque particles can be recovered from
      balloon surfaces after PTCA. Depending upon their size, they could lead to
      coronary spasm or microembolic phenomenon.

PMID- 7625101
TI  - [Cardioverter-defibrillator implantation in the heart catheterization laboratory-
      observations with 105 patients].
AB  - Today, we are facing an exponential increase in implantation of cardioverter
      defibrillators (ICD). The intraoperative and follow-up results are reported in
      105 patients (pts) with ventricular tachyarrythmias who underwent ICD
      implantation in the catheterization laboratory. Fifty-seven pts (54%) hat their
      first ICD implant (G 1), whereas 46 pts (44%) underwent pulse generator
      replacement or electrode revision (2 pts, 2%) (G 2). In all pts, ICD implant or
      pulse generator replacement was performed under general anesthesia from the
      beginning. In 57/58 pts (98%) in G 1, ICD implantation was possible with a mean
      defibrillation threshold (DFT) of 13 +/- 8 joules. One patient hat a DFT of > 25
      joules and ICD implantation was not achieved. This patient underwent epicardial
      lead implantation 1 day later. One patient in G 1 had a vessel rupture (v.
      subclavia) intraoperatively. During a mean follow-up of 5 +/- 2 (< 1-13) months,
      three pts (3%) died from congestive heart failure, 2, 4 and 6 months after device
      implantation. An infection occurred in 1 patient in G 2, 3 months after generator
      replacement. Our data show that in the majority of patients ICD implantation in
      the cath-lab is possible, safe, and the complication rate is low. Therefore, ICD
      implantation in the cath-lab can generally be recommended.

PMID- 7625102
TI  - [Early after-depolarization in polymorphic ventricular tachycardia without QT
      prolongation].
AB  - Endocardial monophasic action potentials (MAP) were recorded at different sites
      of the right ventricle in a patient with a history of syncope and recurrent
      polymorphic ventricular tachycardia (pVT) without QT prolongation. The MAP
      recording from the infero-septal wall demonstrated persisting early
      afterdepolarizations (EAD) during sinus rhythm with no cycle length dependence.
      Programmed ventricular stimulation at this site provoked a pVT rapidly
      degenerating into ventricular fibrillation. Iodine-123-meta-iodobenzylguanidine
      (MIBG) scintigraphy indicated a defective sympathetic innervation in inferior and
      apical sectors of the left ventricle. Intravenous verapamil resulted in marked
      sinus bradycardia and nevertheless completely suppressed the pVT. These
      observations support the hypothesis that the mechanism of pVT is EAD-induced
      triggered activity that is due to an intrinsic defect of the myocardial cell with
      alteration of the calcium channels. This regulation defect of ionic channels
      might possibly be induced by an abnormality in the sympathetic innervation. Both
      conditions may lead to dispersion of repolarization causing triggered activity.
      In our case the regionally restricted findings explain the absence of QT
      prolongation. The effect of verapamil provides evidence that bradycardia is not
      an essential condition in the genesis of pVT.

PMID- 7625103
TI  - [Carotid sinus massage in pacemaker patients with heart rates about the pacemaker
      frequency].
AB  - The delivery of pacing impulses is inhibited in patients with VVI(R) pacemakers
      whose intrinsic heart rate is above pacing rate. Efficacy of the pacing impulse
      can be evaluated on surface ECG by application of a magnet on the pacemaker which
      temporarily induces asynchronous pacing. Carotid sinus massage can alternatively
      lower intrinsic heart rate below pacing rate. The study investigates in how many
      patients carotid sinus massage lowers heart rate below pacing rate during follow
      up, and whether the efficacy is reduced in the presence of a pacing rate
      programmed below the nominal setting. Patients with pacing rates 61-72 ppm (group
      I) were compared to patients whose pacemakers were programmed to 51-60 ppm (group
      II) and 40-50 ppm (group III). A right- and leftsided carotid sinus massage was
      performed in 119 consecutive patients. Right-sided carotid sinus massage was
      positive in 64 and left-sided in 53 patients. The second, left-sided carotid
      sinus massage induced pacing in additional 11 patients. In general, carotid sinus
      massage lowered heart rate below pacing rate in 75 (70%) patients. Induction of
      pacing was significantly lower (p < 0.02) in group III (n = 31/57; 54%) compared
      to group I (n = 17/20; 85%). No differences were detected between group II (n =
      27/42; 64%) and group I. CONCLUSION: Carotid sinus massage is a useful method for
      induction of pacing in patients whose intrinsic heart rate is above pacing rate.

PMID- 7625104
TI  - [Improved evaluation of prosthetic heart valve regurgitation with multiplanar
      transesophageal echocardiography].
AB  - To study the value of the newly introduced multiplane transesophageal transducer
      technology for the assessment of prosthetic valve regurgitation, 63 consecutive
      patients with 35 mitral and 33 aortic prostheses (23 bioprostheses and 45
      mechanical prostheses) were examined. Transvalvular, paravalvular, and, in
      mechanical valves, normal or pathological transvalvular regurgitation were
      identified using first 0 degrees (transverse) and 90 degrees (longitudinal)
      planes combined with flexion of the echoscope tip and then additionally using
      multiple intermediary planes by transducer rotation. In a subgroup of 20 patients
      interobserver variability was evaluated. Both methods showed regurgitation in
      56/58 valves; one additional case of regurgitation was seen by multiplane imaging
      only. However, there were 19 cases of regurgitation not clearly classifiable by
      biplane technique compared to only three using multiplane technique. Grading of
      severity was concordant by both modalities in 66 and discordant in only two
      cases. Observers disagreed on severity in 2/20 cases based on biplane imaging,
      but in none based on multiplane imaging; classification of regurgitation differed
      in 6/20 biplane and 1/20 multiplane images respectively. CONCLUSION: Multiplane
      transesophageal imaging improves classification of prosthetic regurgitation, but
      has little effect on severity grading.

PMID- 7625105
TI  - [Initial experiences with dobutamine stress echocardiography in heart transplant
      patients].
AB  - Cardiac allograft vasculopathy (CAV) has become one of the primary obstacles to
      long-term survival of patients after heart transplantation. The low sensitivity
      of currently available noninvasive tests still remains a problem in the early
      diagnosis of the disease. To assess the feasibility, safety, and usefulness of
      dobutamine stress echocardiography as a noninvasive predictor of cardiac
      allograft vasculopathy, we examined 20 patients (3 female) 3-35 months after
      orthotopic heart transplantation. All patients underwent coronary angiography
      within 2 weeks of dobutamine stress echocardiography. RESULTS: 89% of the
      segments examined could be evaluated for wall motion abnormalities. Under
      increasing doses of dobutamine (5 to max. 30 micrograms/kg/min), heart rate
      increased from 88 +/- 13 bpm to 141 +/- 16 bpm. and systolic blood pressure from
      139 +2- 14 mm Hg to 154 +/- 28 mm Hg. Two of 4 patients with angiographically
      detected CAV developed new wall motion abnormalities under dobutamine; their wall
      motion score increased from 1.23 +/- 0.22 to 1.31 +/- 0.24. In the other patients
      without CAV, the wall motion score remained almost unchanged (1.01 +/- 0.3 to
      1.02 +/- 0.4). Dobutamine was well tolerated, and there were no serious
      complications. Thus, dobutamine stress echocardiography seems to be feasible and
      safe in patients after heart transplantation. Our results suggest that it might
      be useful for the detection of cardiac allograft vasculopathy. The final
      determination of its clinical usefulness in the diagnosis of cardiac allograft
      vasculopathy needs further extensive investigations.

PMID- 7625106
TI  - Persistence of anti-HBs antibodies in health care personnel vaccinated with
      plasma-derived hepatitis B vaccine and response to recombinant DNA HB booster
      vaccine.
AB  - Long-term persistence of specific antibodies after primary immunization against
      HBV infection has been reported. In this study, we evaluated the persistence of
      anti-HBs in vaccinees 6 years after primary immunization and the response to a
      booster dose using a recombinant DNA yeast-derived HB vaccine. An 85.4%
      seroprotection rate was observed after 6 years with a significantly higher
      seroprotective rate in those subjects who received four doses of vaccine primary
      immunization as compared with those who received three doses (93.9% versus 67.2%,
      p < 0.001). One month after receiving the booster dose, 98.6% of the subjects had
      an anamnestic type of response. The GMTs were found to decrease progressively
      with increasing age. The antibody levels after booster dose were higher than
      those attained at the end of primary immunization and reflected the trend seen
      before the administration of the booster. These results are consistent with the
      existence of an effective immunological memory in HB vaccine responders. Subjects
      who received four doses during primary immunization were better seroprotected and
      had a higher seroprotection rate after the booster dose.

PMID- 7625107
TI  - Delivery of class I and class II MHC-restricted T-cell epitopes of listeriolysin
      of Listeria monocytogenes by attenuated Salmonella.
AB  - Using a Salmonella vaccine-Listeria infection model of intracellular infection,
      we studied the capacity of an attenuated strain of Salmonella carrying T-cell
      epitopes of listeriolysin (LLO) of L. monocytogenes to elicit epitope-specific T
      cell responses. Class II (LLO 215-226) or class I (LLO 91-99) MHC-restricted T
      cell epitopes of LLO were inserted within a central, hypervariable domain of the
      flagellin protein of an attenuated delta aroA Salmonella dublin strain. T cells
      from Listeria-immunized mice were activated by lysates or heat-killed
      preparations of Salmonella construct expressing the LLO 215-226 epitope,
      indicating that LLO 215-226 is processed and presented to T cells when offered to
      antigen-presenting cells as part of a flagellin-epitope fusion protein. The
      chimeric flagellin genes were integrated into the chromosome of the flagellin
      negative S. dublin strain to obtain stable expression of the epitopes.
      Immunization with the living, chromosomally integrated Salmonella construct
      carrying LLO 215-226 epitope as part of the flagellin protein generated T cells
      reactive with the corresponding LLO peptide, indicating that this chimera can
      stimulate a class-specific immune response in vitro. The effect of flanking
      residues on the processing and presentation of MHC class I LLO 91-99 epitope was
      studied using Salmonella vaccine strains that express chimeric flagellins
      containing one of three LLO 91-99 inserts: 91-99 (normal flagellin amino acids as
      flanking residues); KK91-99KK (Lys-Lys flanking residues); and AAA91-99AAA (Ala
      Ala-Ala flanking residues).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7625108
TI  - Partial protection against natural trypanosomiasis after vaccination with a
      flagellar pocket antigen from Trypanosoma brucei rhodesiense.
AB  - Cattle that were inoculated with an antigen derived from the flagellar pocket of
      Trypanosoma brucei rhodesiense and then infected with Trypanosoma congolense and
      Trypanosoma vivax were compared with unvaccinated cattle when both groups of
      cattle were placed in regions of Kenya endemic for tsetse flies known to harbour
      T. congolense and T. vivax. In one trial, 90 cattle were employed, 40 untreated
      controls, 30 cattle given prior treatment with samorin, and 20 inoculated with a
      flagellar pocket (Fp) antigen derived from T. brucei rhodesiense, with bovine
      serum albumin as the carrier and alum as the adjuvant. The animals were monitored
      for parasitaemia, by buffy coat analysis, during one rainy season. The untreated
      controls had 58% infection, the samorin-treated cattle had 43% infection, and the
      immunized cattle had 26% infection. Simultaneously, a second trial was conducted
      using 250 cattle, 100 untreated controls and 150 inoculated with the above
      antigen, carrier and adjuvant. At the end of the same rainy season, the untreated
      controls had 22% infection while the immunized animals had 9% infection. In a
      third experiment, on the same ranch as the latter experiment, ovalbumin was
      employed as the carrier. After 15 months, or over three rainy seasons, 13% of the
      untreated controls became infected while of the 177 immunized animals 0.9% became
      infected. These results are the first report of heterologous immunoprotection
      against trypanosomiasis in cattle.

PMID- 7625109
TI  - Mucosal immunoadjuvant activity of liposomes: induction of systemic IgG and
      secretory IgA responses in mice by intranasal immunization with an influenza
      subunit vaccine and coadministered liposomes.
AB  - This paper reports on a novel immunoadjuvant activity of liposomes. An influenza
      subunit preparation, containing the isolated viral surface antigens, was
      incorporated in a liposomal formulation. Administration of this vaccine to mice
      via the intranasal (i.n.) route resulted in a stimulated serum IgG response
      relative to the response to i.n. immunization with the antigen alone. In
      addition, the liposomal vaccine induced a secretory IgA (sIgA) response in the
      mucosa of the lungs and nasal cavity. Both serum IgG and sIgA responses persisted
      up to at least 21 weeks postimmunization. Immune stimulation was observed with
      negatively charged liposomes consisting of phosphatidylcholine (PC), cholesterol
      and dicetylphosphate (DCP), but not with zwitterionic liposomes, consisting of PC
      and cholesterol alone. Remarkably, for stimulation of serum IgG responses and
      induction of an sIgA response, liposomes could be simply mixed with the antigen.
      Moreover, i.n. administration of empty liposomes up to 48 h prior to i.n.
      immunization with the subunit antigen also resulted in immune stimulation,
      indicating that the liposomes did not exert their adjuvant effect by acting as a
      carrier for the antigen. The liposomal vaccine conferred protection against
      infection. It is concluded that liposomes, administered i.n., provide a promising
      adjuvant system for stimulation of antibody responses in general, and mucosal
      sIgA responses in particular.

PMID- 7625110
TI  - Compliance with immunization against hepatitis B. A pragmatic study in sexually
      transmitted disease clinics.
AB  - The efficacy of a vaccine is based primarily on the adherence of the subject to
      the immunization schedule. This paper compares the compliance rates (CR) for the
      third dose of hepatitis B virus (HBV) vaccine given according to one of two
      vaccination schedules among subjects attending two sexually transmitted disease
      (STD) clinics, and the potential influence of place of vaccine administration
      (STD clinic or at a vaccination centre). Heterosexual, anti-HBc seronegative
      subjects (n = 331) were randomized to a 0-1-6 month (n = 161) or a 0-1-2-12 month
      schedule (n = 170) in this prospective, randomized, parallel pragmatic study.
      Some subjects (n = 50) attended and were vaccinated at one STD clinic (centre A),
      whereas 281 attended another clinic (centre B) but were referred to a vaccination
      centre for administration of vaccine. About 31% (103/331) of the subjects
      received at least three vaccine doses. On assessing the CR at the 3rd dose in all
      randomized subjects, we observed that administration of the vaccine at the STD
      clinic attended (A) was associated with a significantly better CR (p < 0.01) than
      that of the subjects referred to a vaccination centre (B), while the CR is not
      affected by the schedule. On the other hand, the 0-1-2-12 schedule was associated
      with a significantly better CR (p = 0.02) at the 3rd dose than the 0-1-6 month
      schedule among subjects who comply with the first two doses; the actual site of
      vaccine administration (in situ (A) versus referred (B)) does not affect the
      CR.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7625111
TI  - Simultaneous administration of oral rhesus-human reassortant tetravalent (RRV-TV)
      rotavirus vaccine and oral poliovirus vaccine (OPV) in Thai infants.
AB  - Rhesus-human reassortant tetravalent (RRV-TV) oral rotavirus vaccine was given at
      the same time as oral poliovirus vaccine (OPV) or inactivated parenteral
      poliovirus vaccine (IPV) to Thai infants at 2, 4 and 6 months of age. Sera for
      rotavirus antibody studies were taken prior to and one month after each
      vaccination. After the first dose of vaccine at 2 months of age, 37% of the
      infants receiving rotavirus vaccine with IPV but only 10% of those receiving it
      with OPV showed a seroconversion by rotavirus IgA ELISA antibody test (p <
      0.001). Likewise, neutralizing antibody seroconversion rates in initially
      seronegative subjects to rhesus rotavirus type 3 (RRV-3) after the first dose of
      RRV-TV vaccine were higher if the vaccine was given with IPV (74%) than if given
      with OPV (39%) (p = 0.0069). After the second and third doses of vaccine, the
      rotavirus IgA ELISA and RRV-3-neutralizing antibody response rates were not
      different between groups. Development of neutralizing antibodies to human
      rotavirus serotypes 1, 2 and 4 in the first seven months of life in vaccinees
      receiving rotavirus vaccine with OPV tended to occur at a lower rate than in
      those receiving rotavirus vaccine with IPV but the antibody levels were not
      significantly different at 7 months of age. Poliovirus type 2 and type 3 antibody
      responses were not different in infants receiving the rotavirus vaccine with OPV
      as compared with infants receiving only OPV. The mean poliovirus type 1 antibody
      level was slightly but not significantly lower at 5 and 7 months of age in
      infants that received both rotavirus vaccine and OPV.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7625112
TI  - Evaluation of a combined tetravalent diphtheria, tetanus, whole-cell pertussis
      and hepatitis B candidate vaccine administered to healthy infants according to a
      three-dose vaccination schedule.
AB  - A vaccine combining hepatitis B with diphtheria, tetanus and whole-cell
      Bordetella pertussis (DTPwHBV) would facilitate the attainment of universal
      vaccination of infants against hepatitis B. A candidate vaccine was administered
      to 42 infants beginning at 7-15 weeks of age. Antibodies were measured from pre-
      and postvaccination blood samples. After three doses, at least 94.9% of the
      infants were protected against hepatitis B, diphtheria and tetanus. Responses to
      B. pertussis were considered adequate. No serious adverse events were reported.
      These results indicate that this candidate vaccine is safe and immunogenic when
      administered to infants according to a three-dose schedule, with doses 2 months
      apart.

PMID- 7625113
TI  - Polysaccharide-iron-regulated cell surface protein conjugate vaccine: its role in
      protection against Klebsiella pneumoniae-induced lobar pneumonia.
AB  - Klebsiella pneumoniae has become an important cause of both community-acquired
      and nosocomial infections. In this study an attempt was made to study the
      immunogenicity of iron-regulated cell surface proteins (IRCSP) alone or in
      conjunction with the polysaccharide moiety of lipopolysaccharide (LPS) of K.
      pneumoniae. The polysaccharide-iron-regulated cell surface protein conjugate (PS
      IRCSP) was non-toxic and non-pyrogenic. It was found to be immunogenic and the
      protection afforded by the conjugate against the challenge strain was observed in
      a rat lobar pneumonia model. The protection observed with the conjugate was
      higher than that observed with polysaccharide or IRCSP alone. The conjugate
      elicited both agglutinating and bactericidal antibodies. Enhanced phagocytosis
      was observed for the alveolar macrophages obtained from the lungs of animals
      treated with conjugate compared with macrophages obtained from animals treated
      with other antigenic preparations.

PMID- 7625114
TI  - Prevention of influenza by the intranasal administration of cold-recombinant,
      live-attenuated influenza virus vaccine: importance of interferon-gamma
      production and local IgA response.
AB  - To clarify which immunological factors were more effective in preventing
      influenza virus infection, we measured immunological parameters induced by
      vaccination and infection in vivo and in vitro. Healthy adult subjects (n = 128)
      were divided into vaccinated (n = 85) and untreated (n = 43) groups. Eighty-five
      were vaccinated intranasally with a trivalent cold-adapted recombinant influenza
      virus vaccine containing type A (H1N1 and H3N2) and B viruses. Subjects were
      mostly seropositive before vaccination. In 29 (80.6%) of the 36 examinees showing
      a prevaccination HI antibody titre of less than 1:128, the titre increased more
      than four times after vaccination. On the other hand, an increase of more than
      four times was found in four (8.2%) of the 49 individuals who had shown a
      prevaccination titre of more than 1:128. The IgA antibody was negligibly detected
      in the nasal wash specimens before vaccination, and was induced by vaccination in
      some cases. Lymphocyte proliferation and interleukin 2 (IL-2) production in
      cultured lymphocytes of the same subjects stimulated by H1N1 virus in vitro were
      correlated with the HI antibody titre. However, the interferon gamma (IFN-gamma)
      production was low before vaccination, regardless of the HI antibody titre, and
      showed a significant increase after vaccination. It was suggested that local IgA
      response and IFN-gamma production play important roles in the prevention of
      influenza. Since there was the outbreak of influenza A (H1N1) in Kochi Prefecture
      after completion of blood samples 6-8 weeks after the second vaccination, we
      examined the above hypothesis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7625115
TI  - Comparison of the efficacy of Brucella suis strain 2 and Brucella melitensis Rev.
      1 live vaccines against a Brucella melitensis experimental infection in pregnant
      ewes.
AB  - The comparative efficacy of Brucella suis strain 2 (S2) and Brucella melitensis
      strain Rev. 1 (Rev. 1) live vaccines in protecting sheep against B. melitensis
      infection was evaluated by clinical and bacteriological examination of ewes
      vaccinated conjunctivally with a dose of 1 x 10(9) c.f.u. when 4 months old and
      then challenged with 5 x 10(7) c.f.u. of the B. melitensis virulent strain 53H38
      (H38) at the middle of the first or second pregnancy following vaccination.
      Animals were considered to be protected when no abortion, no excretion of the
      challenge strain and no infection at slaughter occurred. The percentages of
      protection in Rev. 1-vaccinated groups challenged during either first (80%) or
      second (62%) pregnancy were significantly different (p < 0.001 and p < 0.05,
      respectively) compared with those of the relevant unvaccinated control groups. In
      contrast no significant difference in protection was found between the S2
      vaccinated and control groups.

PMID- 7625116
TI  - Passively administered antibody suppresses the induction of measles virus
      antibodies by vaccinia-measles recombinant viruses.
AB  - We have used vaccinia-measles recombinant viruses to study vaccination in the
      presence of pre-existing antibody. When mice were vaccinated with recombinants
      expressing either the haemagglutinin (H) or fusion (F) measles virus (MV)
      proteins, the humoral response to the MV protein was suppressed by passively
      administered polyclonal antibody. However, individual monoclonal antibodies (H or
      F) did not affect the response. Mice whose anti-MV antibody response to H or F
      was initially suppressed by passive administration of anti-MV antibody were
      revaccinated 120 days later and gave a normal humoral response to the MV
      proteins. The VV-H recombinant induces a strong class I CTL response in Balb/c
      mice. This was not affected by the presence of levels of anti-MV antibody which
      inhibited the humoral response.

PMID- 7625117
TI  - Heterologous HIV-2 challenge of rhesus monkeys immunized with recombinant
      vaccinia viruses and purified recombinant HIV-2 proteins.
AB  - In an attempt to analyse the role of anti-envelope immunity in the protection of
      rhesus monkeys against an HIV-2 intravenous challenge, rhesus macaques were
      immunized twice with recombinant HIV-2 ROD vaccinia viruses (10(8) p.f.u. each)
      at days 0 and 30, followed by booster injections of purified HIV-2 proteins at
      months 8, 9, 15 and 27. One group of five macaques was immunized with the Gag,
      Pol, Vif and Nef antigens, whereas a second group received the same antigens with
      the addition of HIV-2 Env protein. Eight months after the last boost, the animals
      were challenged by intravenous injection of 100 AID50 of a monkey PBMC-grown
      stock of HIV-2 SBL. None of the animals was protected in spite of high humoral
      immune responses on day of challenge as determined by ELISA and Western Blot
      assays.

PMID- 7625118
TI  - HIV-1 recombinant gp160 vaccine induced antibodies in serum and saliva. The NIAID
      AIDS Vaccine Clinical Trials Network.
AB  - As part of a phase I safety and immunogenicity trial of a vaccinia-expressed HIV
      1 recombinant gp160 (rgp160) candidate vaccine, we measured serum and saliva
      antibody responses in low risk, uninfected volunteers. Six healthy adult
      volunteers received 50 micrograms doses of rgp160 vaccine adjuvanted in alum and
      deoxycholate at months 0, 1, 6, and 12. A 200 micrograms rgp160 immunization was
      given to four volunteers at 18 months. The vaccine induced anti-envelope
      glycoprotein IgG and IgA serum antibodies in all six volunteers. Saliva
      antibodies to envelope glycoprotein appeared in some volunteers at certain
      timepoints. Three volunteers appeared to transiently develop vaccine-induced
      secretory IgA antibody to envelope glycoprotein in whole saliva.

PMID- 7625119
TI  - Comparison of the susceptibility of the red fox (Vulpes vulpes) to a vaccinia
      rabies recombinant virus and to cowpox virus.
AB  - Sylvatic rabies can be efficiently controlled by vaccination of foxes with a
      vaccinia-rabies recombinant virus. However, the risk of recombination between the
      engineered vaccine virus and other orthopoxviruses endemic in wildlife, such as
      cowpox virus, still needs to be investigated. In this study, foxes inoculated
      orally and intradermally with cowpox virus were found to be not very susceptible
      to cowpox virus, which was isolated from only the oropharynx and tonsils, at low
      titre and for only five days after inoculation. Thus the risk of recombination
      between these viruses in foxes is very low.

PMID- 7625120
TI  - Good immunogenicity of GBM strain inactivated hepatitis A vaccine in healthy male
      adults.
AB  - A formalin-inactivated aluminium hydroxide adsorbed hepatitis A vaccine was
      evaluated in a dose-response study on 195 healthy male adults (age range: 18-31
      years) in two French hospitals (Lyon, Rouen). Four doses (20, 40, 80, 160 RIA
      antigen units) were administered intramuscularly (i.m.) in two injections over a
      6-month period. At the time of the first vaccine injection, 32 subjects (16.4%)
      were found positive (> 20 mIU ml-1) for HAV antibody (total Ig RIA HAVAB assay,
      Abbott Laboratories) and were excluded from the analysis of immunogenicity
      criteria. Fourteen days after the first vaccine injection, 78.1% (95% confidence
      interval (CI): 62-90) of seronegative subjects who received the 160 RIA antigen
      unit dose seroconverted with a geometric mean titre (GMT) of 43 mIU ml-1 (95% CI:
      33-56). Seroconversion was 100% (95% CI: 91-100) at 1 month with a GMT of 95 mIU
      ml-1 (95% CI: 79-112). Statistical analysis revealed a significant dose-related
      effect (p < 0.0001) on GMT by multivariate regression analysis of the results
      after the first injection. Biological safety was evaluated and alanine
      aminotransferase and aspartate aminotransferase levels were similar prior to and
      14 days after the first injection in the four groups. Reactions after injection
      were similar in the four dosage groups: 6.2% of subjects reported immediate
      reactions after first vaccination (feeling sick, spontaneous pain, headache),
      8.9% reported local reactions at the site of injection (spontaneous pain,
      haematoma, local adenopathy) and 13.5% reported general reactions ('flu-like'
      syndrome, gastrointestinal tract disorders, fatigue, headache).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7625122
TI  - Formaldehyde as an inactivant.

PMID- 7625121
TI  - Bovine T cells preferentially recognize non-viral spacer epitopes in a putative
      FMDV vaccinal peptide.
AB  - In a group of immunized cattle with a variety of MHC class II types, T-cell
      responses were detected to a synthetic peptide (FMDV15) proposed as a basis for a
      vaccine against foot-and-mouth disease. This peptide combines the loop region of
      VP1 with the C-terminal sequence connected by a spacer (PPS). Two major
      immunodominant regions of FMDV15 for bovine T cells were detected, one within the
      loop region and the other around the spacer. A substantial proportion of the T
      cell response to FMDV15 was directed to the spacer region in 5/12 animals, and in
      vitro generation of FMDV15-specific T cells preferentially selected for spacer
      specific T cells. This pattern of response was associated with a particular MHC
      class II type which is very common in cattle. Focusing of the T-cell response to
      non-native virus epitopes may explain why FMDV15 is inefficient at inducing
      protection.

PMID- 7625123
TI  - Comparison of the genome DNA sequences of Bangladesh-1975 and India-1967 variola
      viruses.
AB  - The nucleotide sequences of genome DNAs and the deduced amino acid sequences of
      proteins from potential open reading frames (ORFs) of variola smallpox viruses
      from outbreaks in India in 1967 and in Bangladesh in 1975 have been compared and
      the analyses of the sequences are updated. Alignment of the DNAs revealed 99.3%
      base sequence identity. Of the 200 potential encoded proteins of each virus, 122
      were identical, 42 showed substitution of a single amino acid, 11 showed two
      residues changes, and the remainder were more diverged. The variant proteins were
      encoded mainly in the near-terminal regions of each genome. The most conserved
      region between the variola DNAs included ORFs A33L to A49R, which is a relatively
      poorly conserved region compared with vaccinia virus.

PMID- 7625124
TI  - Role of basic residues in the proteolytic activation of Sendai virus fusion
      glycoprotein.
AB  - Cleavage activation of the Sendai virus (Fushimi strain) fusion (F) protein was
      analyzed by site-directed mutagenesis of the amino acids proximal to the highly
      conserved fusion peptide. In addition, the functional properties of the wild-type
      and mutant proteins were examined to determine their ability to elicit the
      formation of syncytia when co-expressed with the hemagglutinin-neuraminidase (HN)
      glycoprotein. Viral genes were expressed from recombinant T7 transcription
      vectors (pT7/T3 plasmids) containing F or HN genes, after transfection into cells
      previously infected with a recombinant vaccinia virus expressing T7 RNA
      polymerase (vTF7-3). The wild-type F protein sequence (112VPQSRF) which contains
      a monobasic cleavage activation site was altered to include a tribasic, 112VPRKRF
      (mB3), or a pentabasic sequence, 112RRRKRF (mB5) adjacent to the fusion peptide.
      Although addition of basic residues to the normal protein sequence resulted in
      enhanced cleavage activation of the mB3 and mB5 proteins, only the mB5 protein
      was able to induce syncytia formation in CV-1 or HeLa T4 cells. Further analysis
      by the introduction of acidic residues upstream of the cleavage activation site
      was performed to determine whether increased hydrophilicity of the surrounding
      residues might contribute to cleavage activation. The mutants examined, mAcB1
      (104NDDEENAGVPQSRF), mAcB3 (104NDDEENAGVPRKRF), and mAcB5 (104NDDEENAGRRRKRF) all
      contained DEE in replacement for the wild-type TTQ sequence (104NDTTQNAGVPQSRF).
      Analysis showed that only mAcB3 was efficiently cleaved by the endogenous
      cellular proteases, while mAcB1 was minimally cleaved, and mAcB5 not at all.
      Consequently, only the mAcB3 mutant was able to support fusion of CV-1 or HeLa T4
      cells when co-expressed with HN.

PMID- 7625125
TI  - Analysis of Pichinde arenavirus transcription and replication in human THP-1
      monocytic cells.
AB  - Human promonocytic THP-1 cells were previously shown to be nonpermissive for
      Pichinde virus (PV) replication unless the cells were induced to differentiate to
      macrophages by stimulation with phorbol ester (PMA) (J. Virol. 65, 3575, 1991).
      The restriction did not involve receptor modulation, virus binding, nor
      internalization of virus but a requirement for a host cell function in PV
      replication was observed in that the phorbol ester effect required protein kinase
      C activation and was inhibited by actinomycin D. In this report we demonstrate
      that PV S RNA genomes, antigenomes, GPC mRNA and NP mRNA are expressed at high
      levels in PMA treated THP-1 cells but at significantly lower levels or not at all
      in untreated cells. We have also determined that degradation of input viral S RNA
      does not account for decreased PV RNA synthesis in the undifferentiated cells.
      This suggests that the restriction of PV replication in THP-1 cells is a post
      penetration event which precedes transcription of viral mRNAs and replication of
      viral genomes and supports a role for differentiation-specific host cell factors
      early in PV replication.

PMID- 7625126
TI  - The membrane glycoprotein G1 of Uukuniemi virus contains a signal for
      localization to the Golgi complex.
AB  - Members of the Bunyaviridae family acquire their envelopes by budding into the
      Golgi complex (GC). The accumulation of the membrane glycoproteins G1 and G2 in
      the GC probably determines the site of maturation. Here we have studied the
      intracellular transport and targeting to the GC of G1 and G2 of Uukuniemi virus,
      a member of the Phlebovirus genus, and report on their expression from cloned
      cDNAs either together or separately by using a T7 RNA polymerase-driven vaccinia
      virus expression system. When G1 and G2 were expressed together from a full
      length cDNA as the p110 precursor, both proteins were localized to the Golgi
      complex, as evidenced by colocalization with the Golgi marker enzyme mannosidase
      II. Immunofluorescent staining indicated that G1 expressed alone also localized
      to the GC. However, pulse-chase experiments showed that G1 remained
      endoglycosidase H sensitive. G2 expressed alone remained associated with the
      endoplasmic reticulum (ER). G2 could be rescued from the ER and transported to
      the GC by coexpression with G1 from separate mRNAs. Coexpression also increased
      the efficiency of G1 transport to the GC. With none of the constructs could the
      glycoproteins be observed on the cell surface. These results show that efficient
      export of G1 and G2 from the ER requires coexpression of both proteins, in
      conformity with our previous results showing that G1 and G2 form heterodimeric
      complexes in the ER. Since G1 expressed alone is retained in the GC, we conclude
      that G1 contains a retention signal for localization to the GC. G2 might thus
      become associated with the GC indirectly via its interaction with G1.

PMID- 7625127
TI  - Isolation and characterization of TK-deficient mutants of African swine fever
      virus.
AB  - African swine fever virus induces the synthesis of thymidine kinase (TK) in BHK
      TK-negative cells as an immediate early protein. The TK gene is not essential for
      growth of ASFV in cell culture and a stable viral strain deficient in TK has been
      isolated (E70NTKp). The genetic lesion of this ASFV TK- strain was identified by
      TK gene nucleotide sequencing, showing a nucleotide deletion leading to a -1
      frameshift and a nonsense codon residue downstream of the deletion. The
      availability of this viable ASFV variant deficient in TK activity allows the
      insertion of foreign genes in the ASFV genome for genetic and biochemical
      studies.

PMID- 7625128
TI  - Double-stranded RNA adenosine deaminase activity during measles virus infection.
AB  - It has been postulated that the cellular double-stranded (ds) RNA adenosine
      deaminase enzyme is responsible for biased hypermutation during persistent SSPE
      measles infections in humans. As a test of this hypothesis we studied the effect
      of negative-strand RNA virus infection on enzyme activity. The adenosine
      deaminase activity was found in nuclear extracts of both uninfected CV-1 and A549
      cells and in cytoplasmic extracts of A549, but not CV-1, cells. During measles or
      Sendai virus infection of either CV-1 or A549 cells the adenosine deaminase
      activity in the nucleus remained fairly constant up to 24 h post infection, and
      there was no apparent re-partitioning of the enzyme between the nucleus and the
      cytoplasm. Transcription complexes of Sendai virus in vitro or measles virus in
      vivo did not serve as substrates for the enzyme. These data suggest that even
      though some portion of the adenosine deaminase enzyme may be present in the
      cytoplasm of at least some cells during virus infection, modification of the
      viral RNAs by this enzyme, if it occurs at all, must be at a very low level not
      directly detectable by biochemical analysis.

PMID- 7625129
TI  - Sequence analysis of putative pVIII, E3 and fibre regions of porcine adenovirus
      type 3.
AB  - Sequence analysis of a region of the genome of porcine adenovirus type 3 from map
      unit 79.5 to map unit 92 was performed. Homology studies revealed genes coding
      for the hexon-associated protein pVIII on the left and for the fibre protein on
      the right of the sequenced region. By analogy with the genomic organization of
      other adenoviruses, the 1179 bp sequence between the pVIII and fibre open reading
      frames, extending from map unit 81.3 to map unit 84.7, was identified as the
      equivalent of the E3 region of human adenoviruses. The deduced amino acid
      sequence of one of the three open reading frames of the putative E3 region showed
      homology with the 13.3K E3 protein of canine adenovirus type 2. The primary
      structure of the putative fibre protein was similar to that described for human
      adenovirus types 2 and 5, with a 14 pseudorepeat motif in the shaft region of the
      fibre. A 742 bp tandem repeat starting in the middle of the fibre gene and
      extending beyond the termination codon of this gene was observed.

PMID- 7625131
TI  - [International Journal of Food Research and Technology].

PMID- 7625130
TI  - The International Community of Yeast Genetics and Molecular Biology, May 1995.

PMID- 7625132
TI  - [The dopplerographic diagnosis of arterial spasm in patients with subarachnoid
      hemorrhages].
AB  - The paper deals with the specific features of using Doppler transcranial
      sonography in patients with subarachnoid hemorrhage. It describes the advantages
      and disadvantages of the method for the diagnosis of arterial spasm of various
      intracranial arteries. A comparison of angiographic and Doppler sonographic
      findings revealed that the values of the peak systolic velocity of blood flow (r
      = -0.875, p < 0.0001) are the most informative for the diagnosis of the extent of
      intracranial arterial lumenal narrowing. Patients with aneurysm ruptures in the
      internal carotid and middle cerebral arteries were found to have a pronounced
      increase in the blood flow velocity at the site of aneurysm. The intracranial
      arterial blood flow parameters critical for the development of brain ischemia
      during cerebral arterial spasm after subarachnoid hemorrhage are specified in the
      paper.

PMID- 7625133
TI  - [The surgical treatment of erythromelalgia by the destruction of the inlet areas
      of the posterior spinal nerve roots].
AB  - The paper presents a 13-year-old patient suffering from erythromelalgia in whom
      arm pain and burning ceased for 3 years after unilateral stereotactic
      cryodestruction of the thalamic ventrolateral nuclei. Following a relapse,
      reoperation on the other side turned out to be ineffective. Then the patient
      underwent destruction of the inlet areas of the spinal dorsal roots by breaking
      the cervical pain-conducting tracts. Pain and other autonomic manifestations of
      the disease came to an end. The authors give an anatomic and neurophysiological
      rationale for surgery.

PMID- 7625134
TI  - [Acoustic neurinomas. Magnetic resonance tomography using the contrast medium Gd
      DTPA].
AB  - The contrast agent Gd-DTPA was used in the diagnosis of neurinomas of the VIII
      nerve. The analysis of the findings led to the conclusion that the use of the
      agent improved the visualization of auditory neurinomas and contributed to their
      differentiation from the brain stem and cerebellum and that its was more
      advisable to apply contrast enhancement in tumors located in the internal
      acoustic meatus (microneurinomas) or large (including bilateral) tumors with stem
      compression.

PMID- 7625135
TI  - [Short-latency brain-stem auditory evoked potentials in patients with a brain
      concussion].
AB  - The short-latent acoustic stem potentials were examined in 72 males aged 9 to 61
      years (mean 32.3 +/- 10.2 years) with concussion of the brain in different early
      posttraumatic periods (0.5-15 days). The clinical picture of the victims was
      characterized by systemic cerebral and mild transient symptoms of involvement of
      stem regions of the brain. Two thirds of the patients were found to have
      decreased rates of conduction of electric pulses along the acoustic pathway of
      the brain stem. Moreover, a fourth of the victims had a retarded perception of
      acoustic stimuli, which implies that concussion of the brain led to the decreased
      function of the auditory nerve and all relay nuclei of the acoustic system of the
      brain. The normal pattern of short-latent acoustic stem evoked potentials was
      seen in 8.3%, their mild and moderate abnormal changes were observed in 40.3 and
      51.4% of the patients. Prolongation of a latent period and interpeak intervals,
      the deformation and lack of waves were considered to be criteria for abnormal
      changes in short-latent acoustic stem evoked potentials.

PMID- 7625136
TI  - [The retraction pressure in neurosurgical operations on the brain. II. An
      analysis of the complications related to the use of retractors].
AB  - The retrospective analysis of the results of surgical treatment of 1869 patients
      with various neurosurgical abnormalities of the brain who were operated on at the
      N. N. Burdenko Research Institute of Neurosurgery, Russian Academy of Medical
      Sciences, for two randomly chosen years has ascertained that there is a common
      severe complication due to the use of self-held retractors--formation of a
      hemorrhagic infarct area in the brain region exposed to traction. The analysis
      has indicated that the highest incidence of the complication was observed in
      patients with abnormalities of the chiasmal and cellular regions and the middle
      cranial fossa. The complication was absent in patients with aneurysms of the
      anterior areas of the Willis circle.

PMID- 7625137
TI  - [New transplantable brain gliomas in rats].
AB  - The paper provides the characteristics of 11 original transplanted rat brain
      gliomas that are part of the collection of experimental tumors of the nervous
      system, which has been developed at the Institute of Human Morphology, Russian
      Academy of Medical Sciences. The biological features of brain tumour strains,
      methods of their transplantation and cryoconservation are outlined in the paper.

PMID- 7625139
TI  - [A transfacial-transorbital approach to a meningioma of the anterior cranial
      fossa spreading into the orbit and ethmoidal labyrinth].

PMID- 7625138
TI  - [A combination of intracranial aneurysms with primitive carotid-basilar
      anastomoses].

PMID- 7625140
TI  - [The surgical technic for bilateral acoustic neurinomas].

PMID- 7625141
TI  - [The surgical treatment of arterial aneurysms in the acute period of subarachnoid
      hemorrhage].
AB  - The paper presents the surgical outcomes of 300 patients with brain arterial
      aneurysms. A total of 43% of the patients were admitted to the unit within the
      first 72 hours of the onset of hemorrhage, 165 patients were operated on within
      the first fortnight, 135 were operated on in later periods. The aneurysms of the
      anterior communicating artery, internal carotid, middle cerebral artery were 42,
      24, and 22%, respectively. Multiple aneurysms were 12% according to the Hunt and
      Hess classification, the preoperative severity of the patients was as follows:
      Degree I, 39 (13%), patients, Degree II, 130 (43%), Degree III, 106 (36%), Degree
      IV, 18 (6%), Degree V, 7 (2%). In 14% of the patients, aneurysm rupture was
      accompanied by the formation of intracerebral hematoma. The qualitative analysis
      of angiograms revealed vascular spasm in 70% of cases, the quantitative one
      indicated it in 80%. Aneurysm clipping was performed in 269 patients, its
      wrapping with a free muscle flap was done in 31 patients. Among the patients
      operated on, the mortality was 35% in the first fortnight of the onset of the
      disease and 17% during operations in later periods.

PMID- 7625142
TI  - [The use of low-frequency ultrasound in the surgical treatment of CSF
      rhinorrhea].

PMID- 7625143
TI  - [On the centenary of the birth of Prof. I. S. Babchin].

PMID- 7625144
TI  - [Aleksandr Ivanovich Arutiunov (on the 90th anniversary of his birth)].

PMID- 7625145
TI  - A brain MRI study of different types of chronic-progressive multiple sclerosis.
AB  - INTRODUCTION: This study was performed to define the pattern of brain magnetic
      resonance imaging (MRI) abnormalities in chronic-progressive MS (MS). MATERIAL
      AND METHODS: Brain MRIs were obtained for 17 patients with secondary progressive
      MS (SPMS), 14 with primary progressive MS (PPMS) and 5 with "transitional"
      progressive MS (TPMS). RESULTS: Total lesion loads were different for the three
      groups of patients (p < 0.01). At post-hoc analysis, there was no difference
      between patients with TPMS and those with PPMS, while both these groups had
      lesion loads lower than those of patients with SPMS. Patients with PPMS with
      clinical signs indicating involvement of both brain and spinal cord had greater
      total lesion loads than those with clinical isolated spinal cord involvement (p <
      0.05). CONCLUSION: These data indicate that brain MRI patterns of abnormalities
      are related to the clinical manifestations in patients with chronic-progressive
      MS.

PMID- 7625146
TI  - Peripheral neuropathy in multiple sclerosis: a clinical and electrophysiologic
      study.
AB  - Peripheral nerve abnormalities are uncommon in multiple sclerosis (MS). When
      present, they are usually attributed to factors associated with advanced disease,
      such as malnutrition or cytotoxic drugs. We prospectively evaluated 22 mildly
      disabled MS patients with sensory complaints for evidence of neuropathy using the
      Neuropathy Symptom Score (NSS), clinical examination, and electrophysiologic
      studies of peripheral nerves. Distal latency, F-wave response, and nerve
      conduction velocity (NCV) and amplitude in the ulnar, median, tibial, peroneal
      and sural nerves were examined. Neuropathy was recorded if electrophysiologic
      abnormalities were detected in at least two peripheral nerves in the same
      patient. The most frequent electrophysiologic abnormalities noted were prolonged
      F-wave response and low motor amplitude in the peroneal nerve, slow sensory
      conduction velocities of the ulnar and sural nerves, and prolonged distal
      latencies in the sensory ulnar and sural nerves. Electrophysiologic abnormalities
      were found in 33 of 244 nerves examined (14.7%) and occurred in 10 patients
      (45.5%). Neuropathic symptoms were mild and did not correlate with
      electrophysiologic abnormalities. Age, disease duration, disease course and
      neurologic disability as evaluated by the Kurtzke Expanded Disability Status
      Scale, were not associated with the presence of neuropathy. Our findings indicate
      a high frequency of sensory-motor neuropathy in a selected group of MS patients.

PMID- 7625147
TI  - H-reflex modulation during gait in multiple sclerosis patients with spasticity.
AB  - The aim of the present study was to quantitate the Hoffmann (H-) reflex
      modulation in the soleus muscle of spastic multiple sclerosis patients during
      walking at different stimulus strengths, and to quantitate the influence of the
      excitation level of the soleus muscle on the H-reflex. The H-reflex modulation
      was quantified by the minimum H-reflex in the swing phase and the modulation
      index introduced by Yang et al. (1). Stimulus strengths were matched between
      subjects, and only stimuli intensities, which reflect modulation in the H-reflex
      with true neurophysiological origin, were used. Based on this approach, we found
      that the reflex modulation is impaired in moderate spastic patients at both a
      strong and a weak afferent input to the motoneuron pool in consistency with
      studies on severe spastic patients. This study concludes that the H-reflex
      modulation in the spastic patients is only related to the excitation level of the
      muscles, whereas both the excitation level and other factors than the excitation
      level are known to influence the H-reflex modulation in healthy subjects.

PMID- 7625148
TI  - Olfactory function in atypical parkinsonian syndromes.
AB  - INTRODUCTION: Olfaction is markedly impaired in patients with idiopathic
      Parkinson's disease (IPD). This deficit contrasts with reports of preserved or
      only mildly reduced olfaction in patients with atypical parkinsonism. However,
      the sensitivity and specificity of olfactory function testing in the differential
      diagnosis of parkinsonian syndromes has not been studied. In addition, olfactory
      function in patients with corticobasal degeneration (CBD) is unknown. MATERIAL
      AND METHODS: Using the University of Pennsylvania Smell Identification Test
      (UPSIT) with a test score ranging from 0 to 40 we studied olfactory function in
      patients with IPD as well as other parkinsonian syndromes including CBD and
      progressive supranuclear palsy (PSP). RESULTS: UPSIT scores in 118 patients with
      IPD, 29 with MSA, 15 with PSP, and 7 patients with CBD, as well as in 123 healthy
      control subjects revealed a marked impairment in the IPD group in contrast to
      mild impairment in MSA patients and normal olfaction in PSP and CBD patients. An
      UPSIT score of 25/40 was associated with a sensitivity of 77% and a specificity
      of 85% in differentiating IPD from atypical parkinsonism. CONCLUSIONS: These
      results indicate that olfactory function is differentially impaired or preserved
      in distinct parkinsonian syndromes and that it might also have some value as a
      diagnostic pointer. Thus, preserved or mildly impaired olfactory function in a
      parkinsonian patient is more likely to be related to atypical parkinsonism such
      as MSA, PSP or CBD, whereas markedly reduced olfaction is more suggestive of IPD.

PMID- 7625149
TI  - Stimulation of sudomotor axon reflex mechanism by carbachol in healthy subjects
      and patients suffering from diabetic polyneuropathy.
AB  - Sudomotor axon reflex (SAR) mechanism was stimulated by percutaneous
      iontophoresis of carbachol in healthy subjects and patients suffering from
      diabetic polyneuropathy (PNP) of differing severity (stage I-III). SAR response
      was assessed by hygrometry and compared with histamine induced neurogenic
      vasodilation (laser-Doppler flowmetry) and itching sensation (visual analogue
      scale), which may provide information on neuro-secretion and afferent function of
      nociceptive unmyelinated nerve fibers. Carbachol induced long lasting SAR
      response with maximal sweating rates 20-30 minutes after stimulus onset. In
      diabetic patients the carbachol induced SAR response and the histamine induced
      itching sensation were significantly reduced in stage III of PNP. In contrast,
      histamine induced vasodilatation was significantly impaired in all stages of PNP.
      It is concluded that prolonged SAR response following iontophoresis of carbachol
      can simplify evaluation of sudomotor function when compared to established tests
      using intradermal application of acetylcholine. Furthermore, to demonstrate
      impairment of unmyelinated nerve fibers in PNP, histamine induced vasodilatation
      was found to be more sensitive than SAR response.

PMID- 7625150
TI  - A comprehensive electrophysiological evaluation of phrenic nerve injury related
      to open-heart surgery.
AB  - A prospective electrophysiological study of phrenic nerve was performed in 59
      subjects undergoing open-heart surgery. The nerve was stimulated percutaneously
      at the neck and the diaphragmatic response was recorded with surface electrodes
      placed over the 8th intercostal space. The latency, amplitude, duration and area
      of the evoked response were measured before and after the operation. Post
      operatively no response was elicited in 2 patients bilaterally, in 5 from the
      left and in 2 from the right. Comparison of the post-operative with the pre
      operative group values in the remaining subjects showed that the amplitude and
      area of the left phrenic were lower in the post-operative study, indicating that
      some of the nerve fibres were not conducting. There were no statistically
      significant differences between pre and post-operative values of latency or
      duration on the left or any of the parameters on the right. Our findings suggest
      that the amplitude and area of the diaphragmatic response are more sensitive than
      latency in detecting phrenic nerve paresis associated with open-heart surgery.

PMID- 7625152
TI  - Neuropsychological test performance and affect in myasthenia gravis.
AB  - Neuropsychological test performance, including memory, and affect were
      investigated in 16 patients with myasthenia gravis (MG) and in a matched control
      group. Clinical electroencephalograms (EEGs) were recorded from MG patients.
      Cognitive measures included the Randt Memory Test and a number of tests from the
      computerized Neurobehavioral Evaluation Battery which included a test of motor
      speed. Affect was assessed by means of an anxiety questionnaire (IPAT) and a
      computer based questionnaire similar to the Profile of Mood States (POMS). There
      were no significant intergroup differences in memory performance and only an
      isolated significant finding in a timed measure in symbol-digit comparison. The
      MG group revealed significantly reduced finger tapping. Significantly higher
      levels of anxiety, tension, anger, fatigue and confusion were associated with the
      MG group. Abnormal EEGs occurred in 35% of the MG patients, mostly mid-moderate
      diffuse slowing, but in one case epileptogenic activity was present. The failure
      to confirm memory deficits in this study appeared not to be related to age or
      whether patients had generalized or ocular MG. Medication was suggested as a
      possible factor. These, and other variables, need to be evaluated in further
      studies.

PMID- 7625151
TI  - Neuropsychological function in patients with end-stage heart failure before and
      after cardiac transplantation.
AB  - This study was performed to examine cognitive function in patients with end-stage
      heart failure, to identify possible cardiovascular factors associated with
      cognitive function, and to evaluate changes in cognitive function in a subgroup
      of patients who received heart transplantation. An extensive battery of
      neuropsychological tests were given to 62 patients with end-stage cardiac failure
      as part of their evaluation for cardiac transplantation. Most patients were
      consecutive referrals, not selected because of cognitive complaints. A small
      subgroup of transplanted (n = 7) and non-transplanted (n = 4) patients received a
      repeat neuropsychological examination. At initial examination, approximately 50%
      of the patients met criteria for impairment in reference to normal control
      values. Higher stroke volume index and cardiac index and lower right atrial
      pressure were correlated with better cognitive function. In the subgroup of
      patients re-examined, the transplanted patients demonstrated significantly
      improved cognitive function, whereas the non-transplanted subjects were
      unchanged. These data indicate that in patients with end-stage heart failure
      there is a high prevalence of impaired cognitive function which is related to
      measures of cardiovascular efficiency. Preliminary evidence suggests that these
      impairments may be partially ameliorated by cardiac transplantation.

PMID- 7625153
TI  - Delusions and dementia: clinical and CT correlates.
AB  - INTRODUCTION: Delusions occur frequently during the course of Alzheimer's disease
      (AD) and multi-infarct dementia (MID). Their clinical significance and their
      relationship with progression of disease and involvement of selected cerebral
      areas are still unclear. The aim of the study was to determine the clinical and
      CT correlates of delusions in patients with dementia. MATERIAL AND METHODS: A
      series of 67 probable AD and 32 MID patients, underwent computed tomographic
      scans, psychometric tests, neurologic and psychiatric examination, and blood and
      serum tests. RESULTS: Twenty-four patients were found to have delusions during
      the clinical evaluation. Delusional patients showed a significantly higher age
      when compared with non-delusional patients. The results of a multiple logistic
      regression (with stepwise deletion of the redundant variables) of the CT lesions
      on the presence of delusions, showed that only the presence of isolated white
      matter lesions in the frontal lobes were significantly related to the occurrence
      of delusions (Exp B = 3.42; Beta = 1.2; S.E. = 0.6; Sig T = 0.04). Frontal white
      matter changes were significantly related to delusions when a multiple regression
      analysis, entering age and total number of lesions at CT scans, was carried out.
      CONCLUSIONS: We found that focal lesions in the frontal areas were the only
      variable that appeared to be significantly and independently associated with
      delusional disorders.

PMID- 7625154
TI  - Detection of mycobacterial DNA in a patient with neurosarcoidosis.

PMID- 7625155
TI  - Putaminal haemorrhage leading to pure motor hemiplegia.
AB  - Pure motor hemiplegia (PMH) is commonly attributed to lacunar infarction of
      internal capsule or basis pontis. We report 7 patients of pure motor hemiplegia
      as a result of small or moderate size putaminal haemorrhage. All the patients had
      normal median somatosensory evoked potentials. Central Motor Conduction Time
      (CMCT) to upper limb was not recordable in all 3 patients with complete
      hemiplegia. Three of seven patients had complete and four had partial recovery.
      Anterioposterior extension of small or moderate size putaminal haemorrhage seems
      to spare the medially located sensory fibres in the internal capsule. On the
      basis of our results, lateral putaminal haemorrhage should be considered in the
      differential diagnosis of PMH.

PMID- 7625156
TI  - Contrasting histochemical features of various mitochondrial syndromes.
AB  - A comparative histochemical analysis of the prevalence and cytochrome oxidase
      staining characteristics of ragged-red fibres in limb skeletal muscles was
      performed in 19 patients spanning four distinct mitochondrial syndromes: chronic
      progressive external ophthalmoplegia; myoclonus epilepsy with ragged-red fibres;
      mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes;
      and pure limb myopathy. The percentage occurrence of non-ragged red but
      cytochrome oxidase negative fibres was additionally noted. Ragged-red fibres and
      cytochrome oxidase-negative fibres were generally more prevalent in the chronic
      progressive external ophthalmoplegia syndrome than in myoclonus epilepsy ragged
      red fibres syndrome or mitochondrial myopathy encephalopathy lactic acidosis and
      stroke-like episodes syndrome. Isolated cytochrome oxidase-negative fibres were a
      common finding in each phenotypic syndrome except pure limb myopathy and could
      involve any of the major fibre types non-specifically. Ragged-red fibres were
      devoid of cytochrome oxidase activity in chronic progressive external
      ophthalmoplegia, but commonly displayed activity in the other three syndromes
      providing a clue to syndromal differentiation on a histochemical basis.

PMID- 7625157
TI  - Myalgia, neuromyopathy and internalized capillaries: a steroid responsive
      syndrome.
AB  - Exertional myalgia may be due to a variety of neuromuscular diseases including
      glycolytic enzyme defects, carnitine palmityl transferase deficiency,
      mitochondrial myopathies and Becker muscular dystrophy. In few cases it was
      associated with neuromyopathy and internalized capillaries. The latter have also
      been reported in a variety of neuromuscular disorders. We report a patient with
      the latter condition in whom extensive investigations revealed no underlying
      neuromuscular disease. He responded dramatically to steroids on two occasions.
      This syndrome of myalgia, neuromyopathy and internalized capillaries should be
      added to the list of steroid responsive myalgias.

PMID- 7625158
TI  - Mutism developing after bilateral thalamo-capsular lesions by neuro-Behcet
      disease.
AB  - We described a 44-year old right-handed man showing mutism, left hemiplegia and
      pseudobulbar palsy after CT and MRI documented bilateral thalamo-capsular lesions
      by neuro-Behcet disease. Single photon emission tomography (SPECT) and Xenon CT
      revealed hypoperfusion of the bilateral frontal lobes. The pathophysiological
      mechanism of mutism was discussed and we postulate that mutism might occur as the
      result of frontal lobe dysfunction due to the disconnection of thalamocortical
      fiber from thalamus to frontal cortex and that it could be interpreted as an
      incomplete form of akinetic mutism.

PMID- 7625159
TI  - Late diagnosis of Wilson's disease in a case without onset of symptoms.
AB  - Wilson's disease (WD) was diagnosed on the basis of a liver biopsy, blood
      investigations and a radio copper test in a 60-year-old, neurologically normal
      female with uncharacteristic gastrointestinal complaints. Since this patient
      never developed symptoms indicative for WD this case suggests the possibility of
      a subclinical course of untreated WD.

PMID- 7625160
TI  - Immediate prognosis of primary intracerebral hemorrhage using an easy model for
      the prediction of survival.
AB  - We reviewed the medical records and CT scans of 138 patients hospitalized for
      spontaneous supratentorial hemorrhage and conservatively treated. Seventeen
      clinico-anamnestic variables and five CT desumed findings were collected. Using
      univariate analysis we found eight significant predictors of 30-day mortality:
      intraventricular spread (IVS) of blood, volume of the hemorrhage, Glasgow Coma
      Scale (GCS) score, midline shift, hyperglycemia, pupillary abnormalities, limb
      paresis and gaze deviation. With multivariate logistic regression analysis we
      found three independent predictors of 30-day mortality: IVS of blood, volume of
      the hemorrhage and GCS score. Using these three independent variables we
      developed an easy model which allows an immediate estimate of the probability of
      survival with a high degree of sensitivity and specificity.

PMID- 7625161
TI  - In vivo characterization of the multiple sclerosis plaque by magnetic resonance
      imaging and spectroscopy.

PMID- 7625162
TI  - Neural transplantation to the normal and lesioned brain. An experimental study of
      the rat hippocampus.

PMID- 7625163
TI  - Role of the sympathetic nervous system in cardiac performance during
      hyperkalaemia in the anaesthetized pig.
AB  - Cardiovascular performance was studied in 18 alpha-chloralose anaesthetized pigs
      when arterial potassium ([K+]a) was raised to levels observed in heavy exercise.
      The effects of hyperkalaemia were then studied during cardiac sympathetic nerve
      stimulation or during an infusion of noradrenaline. Elevation of [K+]a up to ca.
      10 mM caused a progressive decline in cardiovascular performance. However, right
      cardiac sympathetic nerve stimulation elevated all cardiovascular parameters in
      the presence of raised [K+]a and offset the negative cardiac effects of
      hyperkalaemia. Electrical pacing of the right atrium to heart rates (HRs)
      equivalent to those observed during right cardiac sympathetic nerve stimulation
      did not offset the depressive effects of hyperkalaemia and, indeed, hastened the
      decline in cardiovascular performance. Infusion of noradrenaline (1 microgram kg
      min-1 i.v.) during hyperkalaemia caused an increase in all cardiovascular
      parameters similar to that seen during sympathetic nerve stimulation. After
      propranolol (0.5 mg kg-1 i.v.), sympathetic nerve stimulation slightly increased
      HR, systolic blood pressure (SBP) and dP/dtmax. Elevation of [K+]a occurred more
      rapidly after propranolol, but the heart was still protected from hyperkalaemia
      during cardiac sympathetic stimulation. Infusion of noradrenaline elicited
      arrhythmias in six pigs. Infusion of KCl reduced the incidence of arrhythmias and
      in some cases abolished them. These findings may be related to how the heart is
      protected from exercise-induced changes in potassium and catecholamines.

PMID- 7625164
TI  - Influence of coronary venous retroinfusion and vasodilatation on regional
      myocardial blood flow measurement with microspheres. An analysis of 'microsphere
      loss' from ischaemic and reperfused porcine hearts.
AB  - The influence of coronary venous retroinfusion and a vasoselective calcium
      antagonist felodipine on the microsphere loss in a porcine model of myocardial
      ischaemia and reperfusion was studied. Sixteen open-chest pigs underwent 45 min
      of myocardial ischaemia induced by occlusion of the left anterior descending
      coronary artery followed by 4 h of reperfusion. Either felodipine (felo-retro
      group, 7 nmol kg-1, n = 6) or the corresponding amount of vehicle (vehicle-retro
      group, n = 5) was infused retrogradely into the coronary veins over 30 min,
      starting 5 min before reperfusion. In a third group, the same amount of
      felodipine was administered intravenously (felo-iv group, n = 5). Myocardial
      regional blood flow was measured with radiolabelled microspheres (phi = 15
      microns) injected before ischaemia to investigate a possible loss during
      ischaemia. In the felo-retro group, the apparent blood flow in the ischaemic
      areas, expressed as a percentage of the corresponding values in the non-ischaemic
      areas (%-flow), were 73 +/- 15, 73 +/- 11 and 75 +/- 19 in the subendocardial,
      midmyocardial and subepicardial layers, respectively. The corresponding
      percentage flows were 64 +/- 11, 70 +/- 11 and 62 +/- 9 in the vehicle-retro
      group and 75 +/- 18, 77 +/- 15 and 76 +/- 11 in the felo-iv group. The
      differences between the groups were not statistically significant. It is
      concluded that in this open-chest preparation microsphere loss observed in the
      ischaemic and reperfused myocardium is not increased by coronary venous
      retroinfusion or by a concomitantly administered vasodilative agent like
      felodipine.

PMID- 7625165
TI  - Excitability of the soleus H reflex during graded walking in humans.
AB  - The excitability of the soleus Hoffmann (H) reflex was measured in five healthy
      male subjects during graded treadmill walking. Uphill and downhill walking at an
      8% grade as well as level walking were used to vary the demands for lengthening
      and shortening contractions of the soleus muscle. These changes were assumed to
      cause differences in control of the afferent input in the spinal cord and the
      voluntary output to the soleus muscle. The H reflex was strongly modulated in all
      three walking conditions, high during the stance phase and low or absent during
      the swing phase. The shape of the modulations was, however, different. At uphill
      walking the reflex increased gradually during the whole stance phase and seemed
      to follow the soleus electromyogram (EMG) pattern closely. In the downhill
      condition the reflex excitability increased rapidly at heel strike like the
      soleus EMG and co-contraction of the anterior tibial muscle was observed. At
      level walking a fast rise in reflex excitability was seen just after heel strike
      with low or absent soleus EMG. Mean soleus EMG was lower during downhill than
      during uphill or level walking, but the mean H reflex amplitude was similar in
      all three conditions. However, when the H reflex was related directly to the EMG
      activity by linear regression the reflex gain was lower during uphill walking
      than in the two other conditions. Furthermore, the ratio between H reflex and EMG
      amplitude was high during the first half of the stance phase at level walking
      indicating an elevated reflex excitability independent of the voluntary motor
      output. It is therefore concluded that the modulation of reflexes during walking
      cannot be interpreted in terms of the idea of automatic gain compensation. The
      reflexes must be controlled specifically and independently during the different
      phases of the motor output to meet the mechanical requirements of the movement
      task. Most explicitly this was seen during downhill walking, where an elevated
      reflex excitability together with co-contraction at the ankle joint seem to
      provide increased joint stiffness and security, when the kinetic energy of the
      body has to be brought under control at heel strike.

PMID- 7625166
TI  - The effect of phencyclidine on [3H]GABA and [3H]flunitrazepam binding in the
      brain of naive and handling-habituated rats.
AB  - The effects of handling and handling combined with phencyclidine (PCP) treatment
      on GABAergic neurotransmission were studied in Sprague-Dawley rats. The animal
      material consisted of handling-habituated (HH, for 11 d), acutely handled (naive,
      N), handling-habituated and PCP-treated (10 mg kg-1 i.p., HH + PCP) and acutely
      handled (naive) PCP-treated (N + PCP) and unhandled 'control' rats. The binding
      of [3H]GABA and [3H]flunitrazepam (FLU) was studied with membranes and the
      release of [3H]GABA with slices prepared from the striatum and frontal cortex. In
      the striatum the maximal binding capacity (Bmax) and the binding constant (KD) of
      [3H]GABA were the same in N and HH rats, but in the frontal cortex KD was lower
      in N rats. KD constants of [3H]FLU were significantly lower in both brain areas
      in N rats than in HH rats. After PCP treatment both Bmax and KD for [3H]FLU
      increased in these two brain areas in handling-habituated rats, whereas Bmax of
      [3H]GABA diminished. Neither handling nor PCP had any effect on [3H]GABA release
      from striatal and frontal cortical slices. Handling prior to killing thus affects
      differently the GABAergic parameters studied and modulates the PCP-induced
      effects.

PMID- 7625167
TI  - Acute renal denervation causes time-dependent resetting of the tubuloglomerular
      feedback mechanism.
AB  - Renal effects of acute renal denervation (DNX) were studied in anaesthetized
      rats. In a first series, whole kidney clearance measurements were made 120 and
      240 min after unilateral DNX. At 240 min, urine production was 3.59 +/- 0.87
      microL min-1 in control kidneys and 7.74 +/- 1.97 microL min-1 in denervated
      kidneys. The corresponding values for sodium excretion were 0.56 +/- 0.17 and
      1.41 +/- 0.34 mumol min-1, potassium excretion 0.48 +/- 0.08 and 0.97 +/- 0.37
      mumol min-1 and glomerular filtration rate (GFR) 0.83 +/- 0.08 and 1.05 +/- 0.16
      mL min-1, respectively. In a second series, tubuloglomerular feedback (TGF)
      characteristics were determined with the stop-flow pressure (Psf) technique. With
      increasing time, the sensitivity of the TGF mechanism diminished in denervated
      rats, as indicated by an increased turning point (TP). TP was significantly
      increased 2 h after DNX from 19.1 +/- 1.13 in control to 25.9 +/- 1.10 nL min-1.
      TP was further increased 4 h after DNX to 37.3 +/- 3.12 nL min-1. However, the
      maximal TGF response to increased flow in the late proximal tubule was not
      altered. But, Psf was significantly higher in DNX rats than in the controls (47.4
      +/- 1.01 vs. 43.0 +/- 1.53 mmHg) in spite of a lower blood pressure (107 +/- 2.9
      vs. 119 +/- 2.2 mmHg). We conclude that intact renal nerves are essential for the
      setting of the TGF sensitivity and hence the regulation of GFR.

PMID- 7625169
TI  - Daily energy expenditure in free living minke whales.
AB  - Six minke whales (Balaenoptera acutorostrata) were instrumented with VHF-radio
      transmitters and four with sonic speed-depth transmitters off the west coast of
      northern Norway and Svalbard and followed within view for up to 24 h. During such
      periods their respiratory rate was continuously recorded and their energy
      expenditure estimated according to Folkow & Blix (1992) at different swimming
      speeds and types of activity. We found that cost of swimming is remarkably low in
      these large animals and that their estimated daily energy expenditure on average
      only amounts to 80 kJ kg-1 day-1.

PMID- 7625168
TI  - Lymphatic transport and organ uptake of gelatin and hyaluronan injected into the
      rat mesentery.
AB  - The metabolic pathways of denatured collagen (gelatin) and hyaluronan were
      studied by injecting labelled macromolecules into the mesentery of rats. The
      label, [125]tyramine-cellobiose is trapped intracellularly after endocytosis,
      allowing localization of the site of uptake. Mesenteric and thoracic lymph was
      sampled for 6 h in anaesthetized rats. Separate rats were investigated after an
      awake period of 6 or 24 h. About 30% of the gelatin remained at the site of
      injection and of the remaining activity 1.7% was recovered in lymph, 11% in the
      liver and 15% in the kidneys, whereas 3 h after an intravenous injection of
      gelatin > 70% was recovered in the liver. The change in preferable site of uptake
      from the liver to the kidney was attributed to local degradation in the mesentery
      as confirmed by chromatography of tissue extracts and lymph. Following hyaluronan
      injection and 6 h lymph sampling approximately 30% was left at the site of
      injection and of the remaining activity 5.7% was recovered in lymph. After an
      awake period of 6 or 24 h, 30% was regained in the liver. The recoveries in other
      organs were negligible and mesenteric lymph nodes seem quantitatively unimportant
      in the uptake of hyaluronan or gelatin from lymph or blood. The liver has a
      central role in intestinal hyaluronan metabolism, while denatured collagen is
      more prone to local degradation with remote uptake shared between the liver and
      the kidney.

PMID- 7625170
TI  - The effects of long-term hyperinsulinaemia on insulin sensitivity in rats.
AB  - The effects of long-term exposure (7 wk) to hyperinsulinaemia on insulin
      sensitivity were studied in female rats. The rats were made hyperinsulinaemic by
      implantation of osmotic minipumps that were changed once a week. Elevated
      adrenergic activity and secretion of glucocorticoids were controlled by another
      minipump with propranolol and adrenalectomy with corticosterone substitution,
      respectively. This resulted in hyperinsulinaemia and moderate hypoglycaemia, the
      latter probably counteracted by overeating and increased glucagon secretion, as
      indicated by increased body weight and lower liver glycogen contents,
      respectively. Euglycaemic, hyperinsulinaemic clamp measurements showed a
      significantly higher glucose disposal rate (P < 0.05) in the hyperinsulinaemic
      rats 18.8 +/- 1.1 mg kg-1 min-1 compared with the control groups 14.6 +/- 0.4 and
      15.4 +/- 0.9 mg kg-1 min-1. Insulin stimulation of 2-deoxyglucose as well as
      glycogen synthesis was measured in the extensor digitorum longus muscle, the red
      and white part of the gastrocnemius, the soleus muscle, the liver and in
      parametrial, retroperitoneal, and inguinal adipose tissue. No differences were
      found between the groups in the insulin response of the 2-deoxyglucose uptake.
      Glycogen synthesis was significantly elevated in all muscles in the insulin
      treated compared with the control rats but no differences were found in the
      liver. Capillary density was significantly elevated per unit muscle surface area
      in the soleus and extensor digitorum longus muscles of the insulin-exposed
      rats.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7625171
TI  - Natriuresis obtained by intracerebroventricular infusion of hypertonic NaCl in
      rats with papillary necrosis.
AB  - Raising the sodium concentration in the third cerebral ventricle increases renal
      sodium, potassium and water excretion. The identification and characterization of
      the factor(s) mediating the centrally evoked natriuresis would be greatly
      facilitated if the exact intrarenal effector site were known. We have assessed
      the importance of inner medullary structures for the effects of CNS stimulation
      by examining its ability to alter renal excretion in rats with papillary
      necrosis, induced 2 d earlier with 2-bromoethylamine hydrobromide (BEA), 250 mg
      kg-1 body wt i.v. Male Lewis x DA rats were divided into a BEA-treated group (n =
      6) and a control group receiving vehicle alone (n = 6). In contrast to the white
      papillae normally seen, the papillae of BEA-treated animals were bright red and
      showed a clear line of demarcation at their base. The rats were anaesthetized
      i.p. with Inactin (120 mg kg-1 body wt). Artificial cerebrospinal fluid (CSF) was
      infused (520 nL min-1) via a cannula into the left lateral ventricle. After 45
      min CSF containing 1 M NaCl was used. Stimulation of the control rats with
      hypertonic CSF increased urine flow rate five-fold (5.4 +/- 0.8 to 27.1 +/- 6.1
      microL min-1), Na excretion 23-fold (0.4 +/- 0.1 to 7.6 +/- 1.8 mumol min-1) and
      K excretion fourfold (0.6 +/- 0.18 to 3.8 +/- 0.5 mumol min-1). When the
      concentration mechanisms were damaged with BEA, the basal excretion rates of
      water and Na increased. The natriuretic response to ICV stimulation was severely
      impaired in these rats, but the kaliuretic effect was sustained.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7625172
TI  - Determination of conduction velocity in A-delta and C fibres in humans from
      thermal thresholds.

PMID- 7625173
TI  - Sympatho-adrenergic inhibition of basal and acid-induced changes in duodenal
      motility, mucosal net fluid and alkaline secretion in the anaesthetized cat.
AB  - Experiments were performed on chloralose anaesthetized cats. A 2-cm segment of
      the proximal duodenum was isolated between two luminally situated balloons and
      perfused with isotonic saline containing [14C]-PEG 4000 as a non-absorbable
      marker. The perfusate was analysed with regard to alkalinity (back titration) and
      concentration of marker (liquid scintillation). Net alkalinization and net fluid
      transport were calculated with conventional equations. Motor activity in the
      duodenal wall was recorded as changes in volume of the proximal balloon. In
      presence of sympathetic neural activity (spontaneous or electrically stimulated)
      basal motor activity and mucosal alkaline secretion was low and increased
      minimally in response to luminal HCl (30 mM). Net fluid transport was in an
      absorptive state and shifted to a small secretion upon the acid-exposure.
      Subsequent to bilateral acute splanchnicotomy, or the administration of the
      adrenolytic guanethidine (3-4 mg kg-1, i.v.), spontaneous duodenal contractions
      occurred and the alkaline secretion was increased. Furthermore, both parameters
      were then markedly stimulated by luminal perfusion with 30 mM HCl. Basal net
      fluid transport was zero and turned into secretion upon the acid-exposure. No
      morphological changes of the duodenal surface epithelium could be detected. The
      study demonstrates the existence of splanchnic nerve-mediated, adrenergic
      inhibition of basal, as well as of acid-induced duodenal motility, fluid and
      alkaline secretion.

PMID- 7625174
TI  - Interdigestive gastroduodenal manometry in humans. Indication of duodenal phase
      III as a retroperistaltic pump.
AB  - To elucidate the specific function of the three phases (I-III) of the migrating
      motor complex (MMC) by manometry, detailed analysis of individual pressure waves
      in the proximal duodenum was performed. Twenty healthy subjects (10 men and 10
      women of whom 11 were tube-naive) underwent computerized manometry for 5 h during
      fasting followed by 45 min after a meal using an 8-channel water perfused
      catheter. Three recording points were in the antrum, three in the proximal
      duodenum (2 cm apart), one in the distal duodenum and one in the proximal
      jejunum. In all subjects at least one phase III (median 2) was observed during
      the 5-h fasting recording. In the proximal duodenum the mean proportion of
      retrograde pressure waves, out of all propagating waves, was significantly
      increased in the last part of phase III (85 +/- 9%, mean, SE), compared with
      early phase III (6 +/- 5%), late phase II (5 +/- 4%) and the feeding phase (10 +/
      5%), irrespective of gender or previous tube-experience. The median length of
      the MMCs was 108.5 min. There was no statistically significant difference between
      men and women or between tube-naive and tube-experienced subjects for the duodeno
      jejunal motility indices of phase II and phase III, nor for duration or migration
      of phase III. The postprandial motility index of the small intestine was
      increased compared with the interdigestive late phase II, particularly in the
      jejunum (P < 0.02). The last part of the duodenal interdigestive phase III in
      healthy subjects shows the feature of a retrosperistaltic pump. This cyclic
      sequence of retropropagation coincides with the reported rapid alkalinization of
      the duodenal bulb and the gastric antrum occurring in early antral phase I.

PMID- 7625175
TI  - Fluid and protein secretion from ferret submandibular and parotid glands in
      response to sympathetic nerve stimulation or administration of sympathomimetics.
AB  - Electrical stimulation of the sympathetic innervation evoked secretion of
      submandibular and parotid saliva. By changing the mode of stimulation from a
      continuous to an intermittent one the fluid response increased and glandular
      blood flow improved. The volumes from the submandibular glands were larger than
      those from the parotid glands and further, the protein concentration of
      submandibular saliva was higher than that of parotid saliva. Adrenaline,
      isoprenaline and phenylephrine evoked larger fluid responses from submandibular
      than from parotid glands. However, the fluid response was small compared to the
      parasympathetic one. Substance P-evoked saliva was used as carrier for protein
      released by sympathetic nerve stimulation or administration of adrenaline and
      isoprenaline. In vitro tissues of submandibular and parotid glands responded to
      adrenaline with a dose-dependent release of protein. Taken together, the
      analytical pharmacology performed in vivo and in vitro, and including the
      antagonists phentolamine, dihydroergotamine, propranolol and metoprolol, showed
      that in submandibular glands, alpha(alpha 1)adrenoceptors were predominantly
      involved in fluid secretion and beta(beta 1)-adrenoceptors predominantly involved
      in protein secretion. In parotid glands, fluid secretion seemed solely to depend
      on alpha(alpha 1)-adrenoceptors, while beta(beta 1)-adrenoceptors seemed almost
      solely involved in protein secretion.

PMID- 7625176
TI  - Influences of time intervals between meals and total food intake on resting
      metabolic rate in rats.
AB  - Resting metabolic rate was measured in rats receiving single or double food
      portions every day or every other day, adding up to the same total food intakes.
      Starving rats were also measured. At two different total food intakes, there were
      no differences between the rats that were fed a meal every day and those fed a
      double meal every other day. Thus, the time interval between meals does not
      determine the extent of the metabolic depression. Also, the resting metabolic
      rates of rats fed various reduced food regimens are very similar to each other
      and to the resting metabolic rate of starved rats. The results of this study thus
      indicate that metabolic depression during starvation and severe caloric
      restriction in rats is an initially uniform response that modulates itself late
      in the starvation or restriction period in accordance with the total food intake.

PMID- 7625178
TI  - Vasoactive intestinal peptide regulates angiotensin II catabolism in the rabbit.
AB  - Although vasoactive intestinal peptide (VIP) is natriuretic it stimulates renin
      and aldosterone secretion. Therefore, to effect a natriuresis, VIP may need to
      modulate the sodium conserving actions of the renin angiotensin system (RAS) by
      another means. One possibility is that it alters the rate of disappearance from
      the circulation of one or more components of the RAS. We sought to determine
      whether VIP regulates the rate of catabolism of angiotensin II (Ang II). Steady
      state metabolic clearance studies of Ang II were undertaken with and without
      simultaneous VIP infusion. These studies were performed in rabbits on low, normal
      and high sodium diets, as dietary sodium has been shown to affect the metabolism
      of both VIP and Ang II. The effects of VIP on plasma Ang II concentration and
      secretion were also studied. VIP decreased Ang II catabolism in rabbits on low (P
      < 0.05) and normal sodium diets (P < 0.05). Plasma levels of Ang II increased
      significantly in response to VIP in rabbits on these diets (low, P < 0.04;
      normal, P < 0.05). In contrast, in rabbits on a high sodium diet VIP increased
      the rate of catabolism of Ang II (P < 0.001). Thus we conclude that the effect of
      VIP on sodium excretion may be modulated by its effects on Ang II metabolism. The
      decrease in Ang II catabolism seen in rabbits on low and normal sodium diets may
      prevent or ameliorate any natriuresis while the more rapid degradation of Ang II
      which occurs in dietary sodium excess may enhance the natriuretic effect of VIP.

PMID- 7625177
TI  - Colchicine induces enhanced intestinal permeability in the rat.
AB  - Intestinal permeability was determined in rats receiving colchicine 0.5 +/- 0.15
      mg day-1 in drinking water (30 mg L-1) for periods up to 23 days. The
      lactulose/mannitol method was used to determine whole gut permeability before and
      on days 2, 4, 8, 18 and 23 of colchicine administration. The 8-h urinary
      lactulose excretion following the test meal increased significantly in rats
      receiving colchicine, compared with the pretreatment value. Increased lactulose
      permeability was present after 2 days and remained stable throughout the
      experimental period. Mannitol urinary excretion was not changed. Colchicine
      increases intestinal tight junction permeability by an as yet undetermined
      mechanism.

PMID- 7625179
TI  - Prostaglandin E2 release from dermis regulates sodium permeability of frog skin
      epithelium.
AB  - In the present study we have compared the effects of increased intracellular Ca2+
      in whole frog skin and isolated epithelium (Rana temporaria). Cellular Ca2+ was
      increased by the use of the endoplasmic reticulum Ca2+ ATPase inhibitor,
      thapsigargin. Serosal addition of thapsigargin to the whole frog skin increased
      the Na+ transport by increasing the apical Na+ permeability. This could be
      blocked by the addition of indomethacin or by removal of Ca2+ from the serosal
      solution. The increase in Na+ transport was accompanied by an increased
      prostaglandin E2 release. This indicated that the response in Na+ transport was
      due to a Ca2+ dependent activation of the prostaglandin E2 synthesis. Addition of
      thapsigargin to isolated epithelia inhibited the Na+ transport and had no effect
      on the prostaglandin E2 release, though the prostaglandin E2 release from the
      isolated epithelia could be increased by the addition of arachidonic acid.
      Addition of prostaglandin E2 increased the cAMP contents of the isolated
      epithelia significantly, whereas thapsigargin had no significant effect on the
      cAMP level. Our results demonstrate that serosal addition of thapsigargin causes
      a release of prostaglandin E2 from the dermis below the transporting epithelium.
      The prostaglandin E2 diffuses to the epithelium where it activates the Na+
      transport by increasing cellular cAMP. The epithelium itself does not contribute
      significantly to the prostaglandin E2 synthesis. Furthermore an increase in
      intracellular Ca2+ in the epithelial cells without a concomitant increase in
      prostaglandin E2 release leads to an inhibition of the active Na(+)-transport.

PMID- 7625180
TI  - [51Cr]EDTA for measuring total and single nephron glomerular filtration rate in
      the rat.
AB  - Clearance and micropuncture experiments were performed in halothane anaesthetized
      rats. The aim was a comparison of paired estimates of glomerular filtration rate
      (GFR) from the renal clearance of [51Cr]EDTA (C[51Cr]EDTA) with simultaneous
      estimates of polyfructosan ((Inutest) CIn), 3H,-and 14C-labelled inulin clearance
      (C[3H]In and C[14C]In, respectively) and proximal tubular fluid/plasma
      concentration ratios (TF/P) of [51Cr]EDTA and TF/P ratios of 14C-labelled inulin
      measured in the same samples. C[51Cr]EDTA correlated well with, but
      underestimated CIn by approximately 10%. The correlation coefficient (r) was
      0.92. C[51Cr]EDTA also correlated with, and underestimated C[14C]In by 6%, r =
      0.88, whereas it overestimated C[3H]In by 5%, still with a close correlation (r =
      0.92). Paired data on proximal (TF/P) ratios of [51Cr]EDTA and [14C]inulin were
      collected from early, mid and late proximal convolutions. The data were scattered
      around the line of identity, r = 0.91. It is concluded that [51Cr]EDTA is a valid
      alternative for estimates of total renal and single nephron GFR in rats and has
      the advantage of being less expensive than [14C]inulin.

PMID- 7625181
TI  - Skeletal muscle perfusion in electrically induced dynamic exercise in humans.
AB  - Leg blood flow, blood pressure and metabolic responses were evaluated in six men
      during incremental one-legged dynamic knee extension exercise tests (no load
      exercise-40 W); one performed with voluntary contractions (VOL) and one with
      electrically induced contractions (EMS). Pulmonary oxygen uptake was the same in
      both exercise modes, but the ventilatory coefficient was 2-5 L per L O2 higher in
      EMS than VOL (P < 0.05). Heart rate and mean arterial pressure were slightly
      higher with EMS than VOL at all exercise intensities reaching 138 (EMS) and 126
      bpm (VOL), as well as 148 (EMS) and 137 mmHg (VOL) at 40 W, respectively (P <
      0.05). Leg blood flow, oxygen uptake and conductance were similar in the two
      exercise modes. At 40 W, mean muscle blood flow was close to 200 (range: 165-220)
      mL 100 g-1 min-1, mean peak muscle oxygen uptake reached 230 mL kg-1 min-1, and
      mean conductance became as high as around 45 mL min-1 mmHg-1, and normalized for
      muscle size and arterial pressure it approached 100 mL min-1 100 g-1 100 mmHg-1.
      Lactate and ammonia efflux from the leg were higher with EMS than with VOL and
      the difference became larger with increasing exercise intensity (P < 0.05).
      Muscle glucose uptake was the same in each exercise mode. Femoral venous K+
      concentration increased with exercise intensity and was higher with EMS than with
      VOL, reaching 5.1 (EMS) and 4.7 mmol L-1 (VOL) at 40 W (P < 0.05).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7625182
TI  - Electrical field stimulation of rat mesenteric small arteries: force and free
      cytosolic calcium during neurogenic contractions and mechanisms of non-neurogenic
      relaxations.
AB  - The effect of transmural electrical field stimulation (TEFS) of rat mesenteric
      small arteries was studied. Stimulation parameters were selected to cause
      tetrodotoxin (TTX) sensitive contractions. In arteries precontracted with PGF2
      alpha in the presence of phentolamine, TTX insensitive relaxation could be
      induced by TEFS. The relaxing effect of TEFS required higher stimulation
      amplitude and duration than the contractions. Thus, by appropriately choosing
      stimulation parameters, contractile responses could be elicited which were little
      affected by any relaxing effect, while contractions were abolished by TTX at any
      stimulation conditions in the present study. The contractions were abolished by
      cold storage and almost completely inhibited by phentolamine. Thus, contractions
      were neurogenic and primarily caused by noradrenaline. At low frequencies, TEFS
      caused phentolamine sensitive increases in free cytosolic calcium with no
      contractions. At higher frequencies, there was a further increase in free
      cytosolic calcium, associated with contraction. Only at high frequencies,
      noradrenaline from nerves caused sensitization of the contractile filaments to
      free cytosolic calcium as during stimulation with exogenous noradrenaline. The
      relaxations were associated with decreases in free cytosolic calcium and were
      probably non-neurogenic since they were resistant to TTX, cold storage,
      capsaicin, and repeated stimulation. Furthermore, relaxations were almost
      completely abolished by increasing extracellular potassium to 40 mM or by adding
      tetraethylammonium chloride or 4-aminopyridine. Relaxations were also reduced by
      ouabain and potassium free conditions.

PMID- 7625183
TI  - Prostaglandins and corticosterone in the oviparous female lizard, Podarcis sicula
      sicula, during reproduction.
AB  - The in vitro effects of prostaglandin F2 alpha (PGF2 alpha) and prostaglandin E2
      (PGE2) on corticosterone release by ovarian follicles, corpora lutea (CL), and
      interrenals were studied in the female lizard, Podarcis sicula sicula, during
      reproduction. Follicles and CL studied in the female lizard, Podarcis sicula
      sicula, during reproduction. Follicles and CL were divided according to their
      different developmental stages; follicles: previtellogenic, early-vitellogenic,
      mid-vitellogenic and fully-grown; CL: CL1 (unshelled eggs in the oviducts), CL2
      (shelled eggs in the oviducts), CL3 (eggs laid 6 h previously) and CL4 (eggs laid
      48 h previously). Interrenals were divided according to the reproductive stages:
      pre-vitellogenesis, vitellogenesis, ovulation, post-ovulation, and post
      deposition. PGF2 alpha release was highest in fully-grown follicles and PGE2 in
      early-vitellogenic follicles, corticosterone was highest in pre-vitellogenic and
      lowest in early-vitellogenic follicles. PGE2 decreased corticosterone in pre
      vitellogenic, mid-vitellogenic and fully-grown follicles. PGF2 alpha release was
      highest in CL4, and PGE2 in CL1 and CL2, corticosterone was highest in CL4. PGF2
      alpha increased corticosterone in CL1, CL2 and CL3. In interrenals, PGF2 alpha
      release was highest and PGE2 lowest during ovulation, corticosterone was highest
      during ovulation. PGF2 alpha increased and PGE2 decreased interrenal
      corticosterone during vitellogenesis, ovulation, and post-ovulation. In the
      plasma, PGF2 alpha levels were highest and PGE2 lowest during ovulation,
      corticosterone was highest during ovulation. These results suggest that
      corticosterone, modulated by PGF2 alpha and PGE2, is implied in the reproductive
      processes with different roles. In fact this steroid could favour ovulatory and
      luteolytic processes. In addition the hypothesis of an anti-vitellogenic role of
      corticosterone is discussed.

PMID- 7625184
TI  - Feeding during milking enhances milking-related oxytocin secretion and milk
      production in dairy cows whereas food deprivation decreases it.

PMID- 7625185
TI  - Editorial statement.

PMID- 7625186
TI  - Affective illness in family members and matched controls.
AB  - As part of the US National Institute of Mental Health Collaborative Program on
      the Psychobiology of Depression study, a subset of 460 randomly chosen relatives
      of affectively ill probands were compared to a control group matched by the
      acquaintanceship method. The rate of major affective disorder in relatives was
      found to be 36%; the rate among controls was 28%. Relatives were also found to
      have significantly higher rates of bipolar II disorder, any Research Diagnostic
      Criteria (RDC) affective disorder and any RDC mental disorder. All of these rates
      were found to be significantly higher when female relatives were compared with
      their acquaintances, but only the rate of any RDC mental disorder was higher when
      this comparison was made in men. The acquaintanceship method enabled the
      selection of a control group that closely resembled the relatives, probably to
      the extent of "overmatching". When the match was evaluated to determine whether
      relatives tended to select comparably ill (or well) acquaintances, this was found
      to be the case only for alcoholic and never mentally ill relatives.

PMID- 7625187
TI  - Galactorrhea: subjective response by schizophrenic patients.
AB  - The frequency of galactorrhea and the subjective response to it were investigated
      in 150 schizophrenic patients. The incidence rate was 14% and the prevalence rate
      19%. More than half the women experienced galactorrhea in connection with their
      femininity, with this side effect of neuroleptic therapy being rated more often
      as a positive effect, especially as a reinforcement of feminine identity or as an
      expression of the ability to conceive children. The overall response to
      galactorrhea was positive among 43% and negative among 20%, with the remaining
      patients tending towards indifference.

PMID- 7625188
TI  - The Cantabria first episode schizophrenia study: a summary of general findings.
AB  - This article describes the general findings of the initial cross-sectional stage
      of a prospective follow-up study of all first episodes of schizophrenia that
      occurred in the Autonomous Community of Cantabria over a 2-year period and that
      established contact with any mental health service. The project comprises: i) a 2
      year cross-sectional stage, in which the sample was gathered and studied with
      structured psychiatric instruments such as the Present State Examination and the
      Scales for the Assessment of Negative and Positive Symptoms (SANS and SAPS), and;
      ii) a continuous follow-up. We detected, in the risk age ranged of 15-54 years,
      an incidence of 1.9 per 10,000 inhabitants per year for schizophrenia and of 1.3
      per 10,000 inhabitants per year for the S+ CATEGO diagnosis, without any
      significant gender difference of morbidity. The mean age for the total
      schizophrenic population was 26 years, being significantly higher in women than
      in men. In contrast with what happens with marital status, type of household or
      urban/rural way of life, there was no gender difference in relation to the other
      sociodemographic variables. The way in which nosological and clinical variables
      are associated with first episodes of schizophrenia was also examined in this
      study. We found that 75% of patients reached a maximum CATEGO-ID level, 71%
      received a S+ CATEGO diagnosis, 59% presented first-rank symptoms of
      schizophrenia and that the percentage of a schizophrenic negative syndrome, as
      identified by the SANS and SAPS, was very low.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7625189
TI  - The patients' opinions about curative factors in involuntary treatment.
AB  - The patients' opinions about their treatment are seldom solicited in psychiatry.
      We studied the opinions of 225 patients about curative factors in their treatment
      in a maximum security hospital: 90% answered the questions, which evaluated 38
      forms of treatment. The patients received help from free walking in the hospital
      area in 98% of the patients, holidays in 93%, a personal psychiatric nurse in
      91%, trips in 91%, communication in 88%, personnel's support in 87% and a
      psychiatrist in 86%. Medication was considered helpful in 77% and even
      restriction or isolation in 36% of the patients. If the patient experienced help
      from the psychiatrist, the cross-tabulation revealed that she or he also received
      help from many other treatment forms, even from the isolation. Help from the
      personal psychiatric nurse and medication depended on many other treatment forms.
      The most helpful treatment factors experienced were liberties and interactive
      treatment forms.

PMID- 7625192
TI  - Psychosocial functioning of transsexuals in Belgium.
AB  - Male-to-female (M-F) transsexuals differ consistently from female-to-male (F-M)
      transsexuals in their sociodemographic characteristics, cross-gender and sexual
      history and the degree to which personality disorder is concomitant to their
      transsexuality. As a group, female-to-male transsexuals are more homogeneous.
      Both groups are impaired in their mental functioning, but the male-to-female
      population is more mentally disordered. In a comparison between Dutch
      transsexuals and their Belgian counterparts, the latter were shown to have more
      mental problems.

PMID- 7625190
TI  - First admission with puerperal psychosis: 7-14 years of follow-up.
AB  - The aim of this study was to investigate women who had first-episode psychosis
      within 1 year after parturition. The Danish Psychiatric Central Register and the
      Danish Medical Birth Register were linked to identify all women admitted for the
      first time to a psychiatric department in Arhus County with a psychotic episode.
      Fifty cases were found, giving a frequency of first-episode psychosis within 1
      year after delivery of 1 per 1000. First-episode psychotic disease within the
      first month postpartum occurred in 1 case per 2000 deliveries. The age
      distribution corresponded to that of the background population, but the cases
      were primiparous more often than expected. The socioeconomic status was equal to
      that of a matched control group of obstetric patients. Birth complications did
      not occur more frequently than expected, but the probands had a higher risk of
      preterm delivery than the controls. The clinical picture of the index episode was
      that of manic-depressive psychosis in nearly half of the cases, but no cases of
      schizophrenia were found. Sixty percent of the patients had a picture of severe
      depression, and 20% suffered from manic disorder. The follow-up, 7 to 14 years
      later, was carried out by interviewing the general practitioners. Forty percent
      of the women had not preserved full working capacity due to mental disorder.
      Moreover, the follow-up pointed to schizophreniform symptoms at the index episode
      as a predictor of incapacity to work. Recurrences were very common (60%),
      especially of the nonpuerperal type, and half of the recurrences belonged to the
      manic-depressive disorders.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7625191
TI  - Mortality among patients in psychiatric hospitals in Germany.
AB  - Data from 7 psychiatric hospitals with defined catchment areas were analyzed;
      14,195 episodes of treatment in acute psychiatry wards were recorded within 30
      months. During their stay in hospital 196 patients died, 174 from natural causes
      and 22 by suicide, compared to the expected 32 deaths. Standardized mortality
      ratios (SMRs) were calculated for the different diagnostic and age groups,
      mortality risk being highest in organic mental disorder (SMR 7.55), followed by
      functional psychoses (SMR 4.55) and the "other disorders" (alcoholism, neurotic
      and related disorders, SMR 3.25). Roughly one half of the 196 deaths were due to
      cardiovascular disorders and pneumonia. In patients with nonorganic psychiatric
      syndromes, suicide was the most frequent cause of death (21 of 58 fatalities).
      With regard to the elevated mortality risk of patients with acute mental illness,
      a reduction of fatality rates from natural and unnatural causes should remain a
      major objective of hospital care in psychiatry.

PMID- 7625193
TI  - Cotard's syndrome: analysis of 100 cases.
AB  - In 1880, Jules Cotard reported a clinical state he believed was a new type of
      agitated melancholia. A statistical analysis has been carried out of 100 cases of
      Cotard's syndrome to determine how this clinical concept has fared since its
      inception. In terms of clinical profile, no difference was found between men and
      women or between underlying diagnostic categories; age seemed to increase the
      likelihood of developing delire des negations. Depression was reported in 89% of
      subjects; the most common nihilistic delusions concerned the body (86%) and
      existence (69%). Anxiety (65%) and guilt (63%) were also common, followed by
      hypochondriacal delusions (58%) and delusions of immortality (55). An exploratory
      factor analysis extracted 3 factors: psychotic depression, Cotard type I and
      Cotard type II. The psychotic depression factor included patients with
      melancholia and few nihilistic delusions. Cotard type 1 patients, on the other
      hand, showed no loadings for depression or other disease and are likely to
      constitute a pure Cotard syndrome whose nosology may be closer to the delusional
      than the affective disorders. Type II patients showed anxiety, depression and
      auditory hallucinations and constitute a mixed group. This new grouping cuts
      across the more traditional view and may have therapeutic implications. Authors,
      in general, have considered delire des negations as a syndrome rather than a new
      disease and do not seem to support the view that the completeness of the syndrome
      is a function of presence or severity of depression. The view that delire des
      negations refers only to the delusion of being dead has also carried little
      favour as its likely to waste information.

PMID- 7625194
TI  - Moclobemide and fluoxetine in the prevention of relapses following acute
      treatment of depression.
AB  - The efficacy of moclobemide (378 mg +/- 76 mg/day) and fluoxetine (36 mg +/- 8
      mg/day) in preventing relapse was studied during 12 weeks of continuation
      treatment after a 6-week initial trial. Fifty-nine patients with Hamilton
      Depression Rating Scale (HDRS) scores of 16 or less were enrolled; 29 continued
      to receive moclobemide and 30 fluoxetine. Efficacy was measured using a 17-item
      HDRS, the Montgomery-Asberg Depression Rating Scale and the Clinical Global
      Impression. Improvement in quality of life was measured using a Medical Outcome
      Study Short-form General Health Survey and the 15D Measure of Quality of Life.
      Twenty-three per cent of the patients in the fluoxetine group dropped out of the
      study and 10% in the moclobemide group. Two patients (7%) in the moclobemide
      group and one (3%) in the fluoxetine group suffered a relapse. Health status and
      quality of life improved in both drug groups during a 12-week continuation
      period. The reports of adverse events fell to one third during the continuation
      phase. The results indicate that benefits may be gained from extending acute
      treatment.

PMID- 7625195
TI  - Comparative assessment of saccadic eye movements, psychomotor and cognitive
      performance in schizophrenics, their first-degree relatives and control subjects.
AB  - This study is aimed at detecting biological markers for schizophrenia. For this
      purpose, a total of 70 subjects (21 schizophrenic patients, 27 first-degree
      relatives and 22 controls) performed a series of tests assessing various
      attentional, psychomotor and cognitive functions and saccadic eye movements. The
      schizophrenics performed significantly poorer than both high-risk and control
      subjects in most of the tests demanding attention, concentration and psychomotor
      speed (d2 concentration test, reaction times and Stroop test of perceptual
      interference) as well as cognition (Wechsler intelligence scales). On the other
      hand, these tests did not differentiate between the high-risk and control
      subjects. This distinction, however, could be made by two other parameters:
      hypometria score of saccadic eye movements and ratio of verbal to performance
      intelligence scores. Both parameters were significantly increased in both the
      schizophrenic and the high-risk group, distinguishing both from the control
      group. The relevance of these findings in indicating a schizophrenic disposition
      is discussed.

PMID- 7625196
TI  - Reproductive rates in families of schizophrenic patients in a case-control study.
AB  - Data about the fertility of 142 schizophrenic patients and their ancestors are
      reported and compared with healthy people in a case-control study. The biological
      fitness of the patients is 76% of controls in individuals with at least one
      child, and 48% of controls in all patients, with clear low fertility rates in
      patients, especially in men. When looking at the previous generations, the
      existence of a significant increase in fertility in the relatives of
      schizophrenics was reinforced in the maternal lineage. These results confirm the
      previous findings about the decreasing fertility in schizophrenic patients and
      may be of interest in understanding the maintenance of the illness despite its
      genetic background.

PMID- 7625197
TI  - Negative symptoms and vocational impairment in schizophrenia: repeated
      measurements of work performance over six months.
AB  - Interest in negative symptoms as a dimension of schizophrenia has grown
      dramatically in the last decade. One hypothesized correlate of negative symptoms
      that has received less attention is deteriorated work function. To address this
      issue, this study compared biweekly measurements of work performance for 21
      patients with prominent negative symptom and 29 patients without prominent
      negative symptoms enrolled in a 26-week supported work program. Nonparametric
      analysis indicated that subjects with prominent negative symptoms demonstrated
      poorer performance than other subjects on task orientation, social skills and
      personal presentation. No evidence was found that the work performance of either
      group improved or worsened over time, although a trend suggested that social
      skills may have improved slightly for both groups across the 26 weeks. These
      results support hypotheses linking negative symptoms with deteriorated work
      function.

PMID- 7625198
TI  - Comparison of adult manifestations of schizophrenia with onset before and after
      15 years of age.
AB  - We examined 19 adult cases of early-onset schizophrenia (onset before age 15) and
      19 controls (schizophrenia with onset between age 15 and 35). Being matched by
      sex, length of hospitalization and living environment while the present age
      between groups showed no difference, patients were compared on psychopathological
      symptom measures and intelligence quotient (IQ). Results showed that early-onset
      cases scored significantly higher on Scales for the Assessment of Negative
      Symptoms and had lower performance IQ. No group difference in positive symptoms
      measure from Brief Psychiatric Rating Scale and full IQ was noted. It suggested
      that when early-onset patients grew up, phenomenologically, they resembled the
      schizophrenia of usual early-adult onset in the positive symptom dimension, but
      with more negative symptoms, which may be fundamental in this group of patients.

PMID- 7625199
TI  - Dermatoglyphic patterns in schizophrenic patients.
AB  - Schizophrenics (n = 250) and normal controls (n = 90) were studied to investigate
      and compare their dermatoglyphic patterns. Their fingerprint patterns were
      studied. The frequency of arches in the patient and control groups was similar.
      The frequency of loops in the control group was higher than in the patient group,
      and the trend was consistent in all the digits. The whorls in the patient group
      showed an increase over the control group in all the digits, although this
      finding was not statistically significant.

PMID- 7625200
TI  - Ear disease and schizophrenia: a case-control study.
AB  - The rates of middle ear disease in 70 patients with schizophrenia from a defined
      catchment population were compared with the rates in 359 nonpsychiatric controls
      who were matched for age, sex and general practice. A relative risk (odds ratio)
      of middle ear disease in schizophrenia of 1.92 was found. This was raised to 2.29
      when ear disease occurring after the onset of schizophrenia was excluded.
      Excluding aetiological factors such as brain damage or family history raised the
      odds ratio further to 2.50 and 2.71 respectively. The implications of these
      results are discussed, and it is suggested that middle ear disease may be an
      aetiological factor in some cases of schizophrenia.

PMID- 7625201
TI  - Reproductive behaviour in schizophrenia relative to other mental disorders:
      evidence for increased fertility in men despite decreased marital rate.
AB  - Using case register data, the overall marital rate among 5158 patients with
      mental illness was found to be comparable to the general population. The
      proportion of those ever married was markedly reduced in the schizophrenic group
      relative to those with a manic or neurotic illness. Men with schizophrenia had a
      particularly low rate of marriage. The overall marital fertility of the 3 groups
      was comparable to each other and appeared to be higher than that in the general
      population. In the schizophrenic group only, married men, particularly those with
      a family history of mental disorder, produced more children than married women.
      Men might represent a more fertile group of schizophrenic patients with some
      biological advantage of increased fecundity, which may help to compensate for
      negative selection pressures.

PMID- 7625202
TI  - The clinical impact of reported variance in potency of antipsychotic agents.
AB  - There is significant disagreement on the clinical equivalence (or potency) of
      antipsychotic agents, with up to 500% variance reported in texts. To address the
      extent and consequences of these discrepancies, we took a random sample of 18
      common psychiatry, psychopharmacology and pharmacology texts for antipsychotic
      equivalence tables. We found a marked variation in stated equivalences for the
      majority of antipsychotics. Most affected were the high potency (haloperidol,
      fluphenazine) and newer (molindone) drugs, which had a 500% variance. This
      variation inadvertently contributes to the misuse of these agents. For instance,
      high-potency antipsychotics are prescribed in far larger doses than necessary,
      leading to decreased efficacy and increased side effects. Steps to simplify and
      rationalize the use of these agents are recommended.

PMID- 7625203
TI  - Religious psychotherapy as management of bereavement.
AB  - This study was aimed at determining the effect of psychotherapy in patients in
      bereavement. Fifteen patients in a control group were given brief psychotherapy
      and 15 study group patients received psychotherapy with a religious perspective.
      The patients in the study group showed consistently significant improvements as
      compared with the control group at the end of 6 months. The results indicate that
      highly religious patients with grief and bereavement tend to improve faster when
      a religious psychotherapy is added to a cognitive-behaviour approach.

PMID- 7625204
TI  - Overdose deaths in young substance abusers: accidents or hidden suicides?
AB  - Of 1969 earlier adolescent psychiatric inpatients, 1792 (91%) were traced after a
      mean follow-up period of 15 years. Thirty-nine patients, 2.3% of the men and 2.0%
      of the women had died from drug overdoses. An additional 16 drug- and alcohol
      related deaths had occurred. The overdose death rate increased significantly
      during the observation period. At the time of death, 28 (72%) of the 39 overdose
      cases received a diagnosis of opioid dependence, the rest had polysubstance
      dependence. Death was most often caused by opioids. Comparing the 39 overdose
      cases with 39 surviving controls and 35 suicides from the same patient
      population, we found that the suicide cases had more psychotic symptoms, suicidal
      ideation, learning difficulties and somatic disorders. The suicide cases received
      less follow-up treatment on discharge from hospital, did not enter specific drug
      treatment programs, and were the only ones to be discharged to the street. We
      found no significant differences between the overdose cases and their surviving
      controls. Both groups showed poor impulse control and risk-taking behavior more
      often than the suicide group. The study lends support to the hypothesis that the
      majority of overdose deaths in young drug addicts are accidental poisonings and
      not misclassified suicides.

PMID- 7625205
TI  - Cognitive function, thyroid status and postpartum depression.
AB  - Impairment of cognitive function can occur with thyroid disorder and also with
      depression. Since depression occurs in conjunction with postpartum autoimmune
      thyroiditis, the question arises as to whether any impairment of cognitive
      function in postpartum women is related to change in thyroid status or to
      depressed mood. A total of 242 women (110 thyroid antibody-positive and 132
      antibody-negative) were assessed at 8, 12, 20 and 28 weeks postpartum in the
      outpatients of a district general hospital. Thyroid antibody levels
      (antimicrosomal and antithyroglobulin) were monitored at monthly intervals,
      together with plasma T3, T4 and thyroid-stimulating hormone. The main outcome
      measures were Research Diagnostic Criteria for depression, the 17-item Hamilton
      Depression Rating Scale and the Edinburgh Postnatal Depression Scale, together
      with reaction time and digit span. Subjects with postnatal depression showed
      detectable cognitive impairment independent of thyroid antibody status and actual
      thyroid dysfunction.

PMID- 7625206
TI  - Reliability, validity and factorial dimensions of the Interactive Observation
      Scale for Psychiatric Inpatients.
AB  - The Interactive Observation Scale for Psychiatric Inpatients (IOSPI) is
      characterized by the necessity of interaction between the rater and the patient
      during the evaluation process. The reliability, validity and factor structure of
      the IOSPI were evaluated by using a total of 186 sets of ratings accomplished by
      2 nursing aides on 34 adult psychiatric inpatients submitted to weekly
      evaluations during the 3 first weeks of hospitalization. The patients were
      observed by the 2 nursing aides simultaneously during the morning shift (5 h). In
      the afternoon of the same day, they were interviewed by two psychiatrists who
      filled in separately the Brief Psychiatric Rating Scale (BPRS). Factor analysis
      of the 16 IOSPI items revealed 5 distinct clusters of items, which represented
      higher-order constructs of social interest, psychomotor agitation, psychoticism,
      neatness and irritability. It was found that the IOSPI has significant interrater
      reliability, estimated by an intraclass correlation coefficient of total score
      and factor score. The total scores of the IOSPI showed a significant correlation
      with the total scores of the BPRS, meeting the criteria of concurrent validity.
      The criteria of predictive validity were also met, since the patients who could
      be discharged presented IOSPI scores significantly lower than the patients who
      could not be discharged. In conclusion, the IOSPI met the requirements of an
      evaluation scale and can stimulate therapeutic attitudes of the nursing staff by
      its characteristics of interactive observation.

PMID- 7625207
TI  - Screening instruments for depression and anxiety following stroke: experience in
      the Perth community stroke study.
AB  - Evaluation of the relative efficacy of three screening instruments for depression
      and anxiety in a group of stroke patients was undertaken as part of the Perth
      community stroke study. Data are presented on the sensitivity and specificity of
      the Hospital Anxiety and Depression Scale (HAPS), the Geriatric Depression Scale
      and the General Health Questionnaire (GHQ) (28-item version) in screening
      patients 4 months after stroke for depressive and anxiety disorders diagnosed
      according to DSM-III criteria. The GHQ-28 and GDS but not the HADS depression,
      were shown to be satisfactory screening instruments for depression, with the GHQ
      28 having an overall superiority. The performance of all 3 scales for screening
      post-stroke anxiety disorders was less satisfactory. The HADS anxiety had the
      best level of sensitivity, but the specificity and positive predictive values
      were low and the misclassification rate high.

PMID- 7625208
TI  - Factors affecting illicit and licit drug use among adolescents and young adults
      in Greece.
AB  - A cross-sectional survey on psychosocial issues, drug use, alcohol and health was
      carried out in Greece, with a nationwide probability sample of 2448 respondents
      aged 12-17 and 18-24. Factors potentially associated with illicit and
      unprescribed licit drug use were tested by logistic regression analysis. Several
      predictors were revealed. Sex and age were related to a higher lifetime use of
      illicit drugs, the male young adults reported a higher lifetime use of illicit
      drugs than the females. Positive attitudes toward hashish use, systematic smoking
      and use of drugs by close friends were more closely related to illicit than to
      unprescribed licit drug use. In addition "low self-esteem, family members using
      tobacco and alcohol" and "problematic drinking" were found only to predict
      illicit drug use. Other variables, "family members using drugs with or without a
      doctor's prescription", "being dissatisfied with social life" and "suffering from
      anxiety, depression and depersonalization symptoms" were found to be
      significantly associated with licit but unprescribed drug use.

PMID- 7625209
TI  - The outcome of adolescent suicide attempts.
AB  - A sample of 265 adolescents hospitalized between 1971 and 1980 in a psychiatric
      unit following a suicide attempt was studied to evaluate outcome. After an
      average of 11.5 years, 48% of the original sample, or 127 subjects, could be
      traced. Thirty-nine per cent of these subjects showed signs of improvement, 22%
      appeared to be unchanged and 33% were worse. Substantial dropout rates were found
      in postdischarge care, only 32% of the patients having been followed up for a
      sufficient amount of time. Fifteen subjects had died, only one of whom from a
      natural cause. Of the remaining 14, 5 had committed suicide and 9 had died from
      unnatural or violent causes other than suicide, the cause of death appearing in
      all cases to be closely linked to the subject's adolescent disorders. The
      implications of these findings for suicide prevention are discussed.

PMID- 7625210
TI  - Relationship of parental bonding to child abuse and dissociation in eating
      disorders in Japan.
AB  - Parental bonding patterns were studied in 52 female Japanese eating disorder
      outpatients with and without histories of sexual or physical abuse and with
      dissociation. Instruments included the Parental Bonding Instrument (PBI), the
      Dissociative Experiences Scale (DES) and the Dissociative Disorders Interview
      Schedule (DDIS). Those with physical abuse history, but not sexual abuse history,
      had significantly different parental bonding scores and higher DES scores
      compared with subjects without physical abuse. DES scores and PBI scores were not
      correlated. Although the PBI was useful in discriminating between those with and
      those without abuse histories, it did not detect differences in degree of
      dissociation. Lack of association of sexual abuse to PBI and DES scores may have
      been due to mild abuse.

PMID- 7625211
TI  - Neuropsychological assessment of schizophrenic patients during a psychotic
      episode: persistent cognitive deficit?
AB  - Neuropsychological test performance and clinical symptoms were assessed in 14
      schizophrenic patients at admission to and discharge from an acute inpatient
      psychiatric service. Despite significant clinical improvement at discharge, no
      major change in cognitive performance was observed. Furthermore, patients at
      discharge were significantly impaired compared with normal control subjects case
      matched for gender, age, handedness and level of education. The results suggest
      that some degree of cognitive impairment may be relatively independent from
      schizophrenic symptoms and that such impairment may represent part of a residual
      enduring "trait" vulnerability.

PMID- 7625212
TI  - [A medical editorial policy in Portuguese?].

PMID- 7625213
TI  - [The centenary of x-rays].

PMID- 7625214
TI  - [The prevalence of measles, rubella, mumps and chickenpox antibodies in a
      population of health care workers].
AB  - We present an epidemiological and serological study in 409 health care workers
      randomly selected from the 4,103 workers of the University Hospital of Coimbra. A
      low level of susceptibility for measles (1.2%; 95% confidence interval (95% CI):
      0.15-2.23%), rubella (2.4%; 95% CI: 0.9-3.9) and varicella (3.2%; 95% CI: 1.5
      4.7%) and a very high one for mumps (17.3%; 95% CI: 13.7-21.1%), were found.
      Ineffectiveness of historical information in predicting immune status to all of
      these diseases was found. An economic analysis of preventive measures was done. A
      mumps vaccination policy for health care workers is recommended and the
      opportunity of measles and rubella vaccination is discussed, facing the results
      of this study. Continuous monitoring of these diseases is needed anticipating the
      changes in epidemiology that are expected to occur with childhood vaccination.

PMID- 7625215
TI  - [The epidemiology of proximal femur fracture at the Hospital da Horta (Azores)].
AB  - The aim of this study was to know the incidence of osteoporotic hip fracture in a
      defined area of the Azores. The catchment area included the islands of Faial,
      Pico, Flores and Corvo, with 11,617 subjects aged 50 or more: 5,373 males and
      6,244 females. The time period of the survey was 1991 to 1993. Data was obtained
      from the records of the Orthopedic Department of Hospital Horta. Thirty seven
      fractures were diagnosed during the time survey: 12 in 1991, 13 in 1992 and 12 in
      1993. The age-adjusted mean incidence rates of hip fracture for the population
      over 49 years old was 10.3/10,000: 5.6/10,000 in men and 14.4/10,000 in women.
      Most fractures occurred in women over the age of 65 years. The ratio of male to
      female cases was 1:3. The mean age of all patients was 77 +/- 8 years of age: 72
      +/- 8 in males and 79 +/- 6 in females (p = 0.05). About 70 percent of these
      patients were treated surgically. The acute mortality rate was 8 percent and the
      mean age of the deceased patients, 82 +/- 6, was significantly higher than the
      mean age of the survivors, 73 +/- 6 (p = 0.01).

PMID- 7625217
TI  - [Acute pulmonary edema. The therapeutic approach].
AB  - The management of acute pulmonary edema remains an interesting challenge to the
      clinician. The early recognition of this frequent condition, based on clinical
      features, must lead to the institution of general measures of therapy that can
      save most patients; a delay or mistake in this early treatment is lethal. The
      subsequent treatment depends on the characterization of the etiology and the
      pathophysiological characteristics of each case. The authors present a review of
      the management of acute pulmonary edema for the general practitioner, which
      includes the general first line measures and also mention some therapeutic
      approaches, related to different etiologies, namely those requiring intensive
      care units.

PMID- 7625216
TI  - [Echo endoscopy in the local staging of gastric cancer].
AB  - OBJECTIVES: to evaluate the accuracy of endoscopic ultrasonography (EUS) in the
      pre-operative T and N staging of gastric cancer. PATIENTS AND METHODS: 41
      consecutive patients with gastric cancer (35 carcinomas and 6 lymphomas)
      underwent EUS using an Olympus GF-UM20, with 360 degrees sector scan and
      interchangeable frequency (7.5-12 MHz). They were classified as T1-T4 and N0-N2,
      according to the TNM system. These results were then compared with the surgical
      and pathological staging (SP), by the weighted K statistic (Kw). RESULTS: In 2
      patients EUS staging was not possible due to cardiac stenosis and in other 4
      patients, information about SP staging was not available. In the remaining 35
      patients the EUS/SP agreement was good (Kw = 0.80) for stage T and moderate (Kw =
      0.49) for stage N. Non-agreement was mostly due to EUS understaging, both T and
      N. CONCLUSIONS: 1) EUS is the most accurate procedure for pre-operative local
      staging of gastric cancer, and 2) EUS should preferably be performed by
      endoscopists with sonographic experience and a particular interest in the method.

PMID- 7625218
TI  - [The diagnosis and treatment of fibromyalgia].
AB  - Fibromyalgia syndrome (FMS) affects predominantly females and is characterised by
      widespread musculoskeletal pain, fatigue, insomnia, nonrefreshing sleep, diffuse
      stiffness and other organic and psychic signs and symptoms. Diagnosis is
      essentially based on the 1990 American College of Rheumatology Classificative
      Criteria, but if, in some cases, they are not completely fulfilled, diagnosis is
      not excluded in a particular patient. The causes of the enhanced pain perception
      and of all the other clinical characteristics are unknown. Both the central
      hypothesis (sleep disturbance; psychological affection; hypothalamus-hypophysis
      adrenal axis disorder; neuromediators disregulation; etc.) and the peripheral
      theory (anatomical and/or functional muscle disturbance) try to explain FMS
      etiopathogenesis. Tricycles antidepressants (i.e. amitriptilin) and some muscle
      relaxants (i.e. ciclobenzaprine) have demonstrated some beneficial effect
      contrary to the classic antirheumatic drugs (NSAID; corticosteroids; etc.).
      Physical exercise, multidisciplinary support (behavioural therapy, physical
      agents; etc.) and patient education are some of the other approaches which
      contribute to the correct management of FMS.

PMID- 7625219
TI  - [Sinus pericranii and developmental venous anomalies: a frequent association].
AB  - The authors describe 2 cases of congenital sinus pericranii associated with
      intracranial venous anomalies. After a review of the literature concerning this
      association they consider the possible etiopathogenic mechanisms and treatment
      implications.

PMID- 7625220
TI  - [Hepatocellular carcinoma. Rare forms of presentation].
AB  - The occurrence of metastases is documented in a varied number of hepato-cellular
      carcinomas (HCC). The indicative metastasis is very rarely the form of clinical
      presentation of the disease. Two cases of HCC which were clinically presented in
      a secondary location, in the bone and skeletal muscle respectively, are
      described.

PMID- 7625221
TI  - [Cytomegalovirus-induced colitis in HIV infection. Considerations on its
      diagnosis, treatment and complications].
AB  - The diagnosis of cytomegalovirus intestinal disease in patients with HIV (human
      immunodeficiency virus) infection frequently raises diagnostic problems in view
      of the absence of definite pathological, serological or virological markers of
      active CMV infection. We describe the case of a 47-year-old man with a CMV
      colitis which illustrates several diagnostic and therapeutic problems and that
      was complicated by an intestinal perforation. We emphasize that in HIV+ patients
      with chronic diarrhea, the presence of abdominal pain should suggest the
      possibility of a CMV colitis and that in such cases a colonoscopy with biopsies
      of the right colon should be performed, in view of the higher frequency of the
      typical histopathological changes at this level. On the other hand, this case
      presented a marked thickening of the colon wall, simulating pseudotumoral images
      on CAT scans, as recently described in literature. The therapeutic possibilities
      as well as the complications of CMV colitis are discussed in the context of the
      occurrence of an ileal perforation, which represents the first report of this
      complication in Portuguese literature and which had the particularity of having a
      long survival after surgery in comparison with the previous cases described in
      international literature.

PMID- 7625222
TI  - [Neuropathy in Waldenstrom's macroglobulinemia].
AB  - The association of a neuropathy and a paraproteinaemia such as Waldenstrom's
      macroglobulinaemia is frequent and not fortuitous. This paper reports a slowly
      progressive, predominantly sensory neuropathy, occurring in a 69-year-old man, as
      the first sign of a Waldenstrom's macroglobulinaemia. A saphenous [correction of
      sural] nerve biopsy revealed a mixed process of primary demyelination and axonal
      degeneration. Accumulations of immunoglobulin M were observed in the myelin
      sheets and the perineurium by immunocytochemistry. Infiltrations of inflammatory
      blood cells and accumulations of amyloid material were absent in the peripheral
      nerve. The axonal loss was most prominent in central areas of the nerve
      fascicles. This find supports the hypothesis of an ischemic mechanism for the
      axonal degeneration plus secondary demyelination, associated to a direct
      immunological attack against myelin. The various types of peripheral nerve
      involvement in Waldenstrom's macroglobulinaemia, as well as the admitted
      mechanisms of nerve lesion and the therapeutic approaches to this still unclear
      neuropathy are briefly reviewed.

PMID- 7625224
TI  - [Care, processes and archive].

PMID- 7625226
TI  - [Acute pancreatitis. An analysis of 91 consecutive cases (1988-1991) with a brief
      review of the literature)].
AB  - Acute pancreatitis (AP) remains a subject of great controversy from the
      standpoint of its aetiology, pathogeny and treatment. We present a study of 91
      patients with AP consecutively admitted to a surgical ward. 50 Women and 41 men
      with a mean age of 59 +/- 19 years were treated. The aetiology of AP was
      attributed to gallstones in 54 patients, alcohol in 22, ERPC and trauma; in 14
      patients the aetiology was considered idiopathic. The most frequent signs and
      symptoms were pain, vomiting, abdominal tenderness, jaundice and fever. The mean
      number of Ranson's prognostic criteria was 3 +/- 1.5 and 29 patients (31%) had
      more than three. Initial management was conservative in 84 patients (92.3%) and
      seven were operated on admission (acute abdomen in four, septic shock in two and
      common duct obstruction in another). Mortality rate was 11% (n = 10) and in 24
      patients (26.3%) there were complications of AP. Most of the patients (80%) began
      oral feeding a week after admission. The mean number of Ranson's criteria of
      patients deceased was 5.4 +/- 1.6 and of those who survived was 2.8 +/- 1.3 (p <
      0.001). Follow-up of patients allowed us to see that in five (5.5%) there was a
      relapse of AP.

PMID- 7625225
TI  - [Orphan diseases and drugs].

PMID- 7625223
TI  - [The Medical School of Campo Santana].
AB  - The Medical School of Campo Santana was built on the site where the bullring once
      stood. It replaced the Medical-Surgical School of Lisbon, in the vicinity of S.
      Jose Hospital, which was in a state of impending ruin. Despite this concern,
      construction was slow and only twenty years after laying the first stone was it
      possible to begin lectures in this new building. It is a majestic edifice with
      contributions by the best artists of the era: panels by Veloso Salgado in the
      Actos Room, tiles by Jorge Colaco in Passos Perdidos, and paintings by Colombano
      in the Council Room. Reference is made to some historical events which took place
      in this building. With the transfer of medical studies to Santa Marta Hospital,
      the Medical School of Campo Santana suffered a period of neglect which ended with
      the founding of the Faculty of Medical Sciences of Lisbon in 1977.

PMID- 7625227
TI  - [The assessment of functional status in the elderly. The application of a
      Portuguese version of the COOP/WONCA charts].
AB  - INTRODUCTION: The outcomes of medical care can be measured in terms of health or
      functional status. Several outcomes measures have been developed in the last
      years but, there are several difficulties with cross-cultural adaptations. This
      study is mainly an application exercise to a group of old people of a Portuguese
      version of the COOP/WONCA charts. METHODS: A descriptive cross-sectional study
      with a component of qualitative analysis was done. Population basis was the
      elderly registered in the lists of five family doctors in two Portuguese health
      centres (Lumiar and Costa da Caparica) in the Lisbon region. A random sample of
      189 patients (aged 65 and over) was interviewed. The studied variables were:
      gender, age, civil status, literacy, co-morbidity and dimensions of the
      COOP/WONCA charts. Univariate and bivariate analysis was done. A qualitative
      analysis was also performed to approach relevancy and acceptability of the charts
      to the elderly. RESULTS: 23% of the elderly had important limitations (values 4
      and 5 of the charts) in physical fitness, 25% had unfavourable repercussions in
      feelings (values 4 and 5), 12% had important difficulties (value 4 and 5) in
      every-day life activities and 7% had important limitations in social life. 66%
      had no changes in their health in the last two weeks, 18% got better and 16% got
      worse. 21% valued their overall health as fair or poor, 47% as good and 24% as
      very good or excellent. Moderate to severe pain in the last two weeks was
      reported by 55% of the patients. Female reported in general worse scores than
      males. Statistical significance was found in the association between the number
      of the co-existent health problems in the same person (co-morbidity) and the
      values of some dimensions of the COOP/WONCA charts. In the half of the cases
      where the Katz index was measured there were non-concordance with the measures of
      the daily life of the COOP/WONCA charts. The charts had good acceptability and
      applicability but also some difficulties for illiterate elderly. DISCUSSION:
      Although the use of COOP/WONCA charts could be difficult with elderly patients
      the present study showed its applicability and utility in the everyday clinical
      practice. The charts open new possibilities for international comparisons on
      functional status assessment.

PMID- 7625228
TI  - [An analysis of plasma histaminase in schizophrenic patients and its relationship
      to clinical parameters].
AB  - Previous studies have investigated putative alterations in histamine and
      histamine receptors in schizophrenia, and evidence in favour of the role of this
      amine as a neurotransmitter or as a neuromodulator was found. In the present
      study the activity of plasmatic histaminase was analysed, with histamine and with
      cadaverine as substrates, in a group of 23 schizophrenic patients and compared
      with that of healthy controls (n = 32). Plasma histaminase activity was
      determined using Gordon and Peters spectrophotometric method, and the results
      were expressed in mumoles of H2O2 transformed/hour/litre of plasma at 25 degrees
      C. Plasmatic histaminase, using histamine as substrate, was significantly
      increased in schizophrenic patients as a whole compared with the healthy
      controls. On the other hand, when cadaverine was used as substrate plasma
      histaminase was significantly reduced in female schizophrenics but not in males.
      When patients were divided according to 17 clinical characteristics it was found
      that the following subgroups were significantly associated to high levels of
      plasma histaminase (using histamine as substrate): the non mentally deteriorated
      schizophrenic patients compared with mentally deteriorated schizophrenic patients
      and those with thymic symptoms as opposed to those without thymic symptoms. An
      extension of this series and a prospective analysis are required to further
      define the clinical and biological significance of the alteration of this
      biochemical parameter in schizophrenia, and particularly in relation with a
      subgroup of schizophrenia with a more favourable course.

PMID- 7625229
TI  - [Albumin. From physiopathology to therapeutic use].
AB  - Albumin has multiple roles in homeostasis. The importance of serum albumin in
      colloid oncotic pressure has been overemphasized. Albumin supplementation must be
      supported by pathophysiology and the achievement of specific objectives.

PMID- 7625232
TI  - [Congenital rubella. Still with us].
AB  - After vaccination against rubella was introduced, the number of cases of rubella
      and congenital rubella syndrome decreased significantly. The presentation of a
      case report of rubella virus congenital infection with important sequellae,
      stresses the need to reinforce prevention. The existence of rare cases of
      reinfection imply good surveillance that gestations should be maintained even in
      women previously immune.

PMID- 7625230
TI  - [Osteoporosis in adult men].
AB  - Osteoporosis in men, despite being a less important public health problem than
      osteoporosis in women, should not be neglected as it has many deleterious effects
      as well as social and economic costs. Finding the cause of osteoporosis is more
      complex in men than in women, and prevention should be based on an early
      evaluation of the various possible risk factors and on taking up measures that
      tend to maximise the peak bone mass. Further studies need to be carried out in
      order to establish the differences and similarities that characterise this
      phenomenon when considering different sexes.

PMID- 7625233
TI  - [Nonalcoholic steatohepatitis].
AB  - The authors present a case of a nonalcoholic steatohepatitis, with progression to
      liver cirrhosis in an obese female patient. A review of the literature, possible
      evolution, and principle pathological processes involved is made. Attention is
      drawn to obesity as a risk factor in the progression of steatohepatitis and the
      advantage of performing liver biopsies in selected cases as a fundamental
      technique of diagnosis.

PMID- 7625234
TI  - [An epidemiological study of bronchial asthma in a population of schoolchildren
      in the Azores (Faial)].

PMID- 7625231
TI  - [Neurosyphilis and AIDS].
AB  - Syphilis in HIV-infected patients reveals some particular aspects which are
      clinically relevant and disturbing: it is more frequent and develops more quickly
      to late stages, namely neurosyphilis; this progression may happen even if classic
      therapy in the early stages has been undertaken; the diagnosis of neurosyphilis
      is rather complex, the serological tests being of no definite credit; high doses
      of intravenous penicillin should be administered for a long period. We report a
      case that exemplifies the aspects described above.

PMID- 7625235
TI  - [Comorbidity of panic disorder and social phobia].
AB  - Among 83 patients presenting panic disorder 24% have comorbid social phobia. Its
      age of onset was earlier than the one for panic disorder, in 95% of social
      phobics appeared first. Patient comorbid with social phobia and panic disorder:
      a) have an earlier panic disorder age of onset (p < 0.05); b) have more major
      depressive disorders (p < 0.01); c) more obsessive compulsive disorders (p <
      0.05); d) higher scores in all SCL-90 subscales, except for phobias; e) more
      severity in the social phobia scale from the Fear Questionnaire of Marks &
      Mathews. The clinical significance of these findings is discussed.

PMID- 7625236
TI  - [A study of the locus of control in patients with renal transplants].
AB  - The locus of control (using I-E Rotter' Scale) maximum psychosocial adjustment
      level (according to Axis V of DSM-III) and other sociodemographic data were
      assessed in 31 patients with renal transplantation. 51.5% of the patient were not
      psychosocially adapted, and externality was the predominant locus of control. As
      far as psychosocial adjustment is concerned, no variation in the absolute as
      found in terms of Internality-Externality. Finally, there was a statistically
      significant correlation between some items of the Rotter' scale and psychosocial
      adjustment.

PMID- 7625237
TI  - [Cerebral blood flow and post-TIA depression].
AB  - OBJECT: This study tries to evaluate the hypothesis of an association between
      severity of post-stroke depression and reduced cerebral blood flow (SPECT Xenon
      133). METHOD: 37 patients in the fourth week of post-stroke evolution with RDS
      criteria of major depression (N = 20) and non-depressed patients (N = 17) were
      compared in regard to following parameters: values of cerebral blood flow (SPECT
      Xenon-133), localization of brain lesion (CT Scanner) and quantitative
      measurement of mood (HDRS, MARDS, BDI), functional ability (Barthel, Karnofsky),
      cognitive function (MMSE, WPT) and neurological function (Orgogozo's Scale).
      RESULTS: Post-stroke major depression is more frequent (NS) in left and anterior
      lesions. We also demonstrated a significant association between total brain
      hypoperfusion and 1) severity of post-stroke depression, 2) severity of
      neurologic and functional impairments. CONCLUSION: these results suggest a
      relationship between mood and cerebral perfusion following stroke.

PMID- 7625238
TI  - [Personality disorders in a psychiatric unit: retrospective study].
AB  - From those patients who were admitted to the psychiatric in-patient unit of the
      Hospital Ramon y Cajal of Madrid across a period of eight years, those who
      received a diagnosis of personality disorder according to the axis II of DSM-III
      or DSM-III-R were selected. We analyzed the patterns of comorbidity between axis
      I and II, length of the admission, the percentage of readmissions and general
      variables as age and sex. 17.35% of the patients admitted for the first time and
      27.03% of those readmitted received a clinical diagnosis of personality disorder.
      The most frequent disorders were: unspecified, histrionic, obsessive-compulsive
      and dependent. In the 93.81% of the patients admitted for the first time,
      comorbidity with axis I disorders was found. Cluster A personality disorders were
      most frequently associated to schizophrenia and delusional disorder, cluster B
      diagnoses with dystimia and alcohol-related problems and cluster C disorders with
      depression, dystimia and OCD. The cluster A was the one that presented more
      frequently without axis I comorbidity (14.28%). Cluster B disorders were
      associated with a shorter length of the admission but, as the unspecified
      personality disorder, were readmitted more frequently. We discuss the results and
      compare them with those obtained by other authors.

PMID- 7625239
TI  - [Study of the evolution of some monocytic parameters and neuroendocrine function
      tests in depressed patients].
AB  - BACKGROUND: The development, evaluation and use of biological markers is
      extremely important in Psychiatry. However, with certain exceptions, truly
      sensitive and specific markers have not still emerged. Several studies have
      reported immune cellular and humoral dysfunction during depression. We
      specifically focused on the study of the monocyte because it has a key role in
      the activation of the immune response. We also investigated the relationship
      between the immune apparatus and the hypothalamic-pituitary activity in depressed
      patients. METHODS: We used a longitudinal design and assessed monocyte parameters
      (HLA-DR, CD 35, vimentin filaments and phagocytosis index) and neuroendocrine
      tests (DST and TRH-test) at intake (pretreatment phase: phase I) and at follow-up
      (post-treatment phase: phase II) in 49 depressed patients according to Research
      Diagnostic Criteria (RDC). The mean follow-up interval was 12.2 +/- 2 weeks. The
      severity of illness was measured by means of the Hamilton Depression Rating Scale
      (HDRS). RESULTS: Seventy per cent of patients showed a pretreatment marked
      monocyte dysfunction (82.5% had at least one parameter altered). After treatment,
      alterations in immunological variables were significantly associated (p < 0.05)
      with depression scores higher than 15). We did not find any significant
      association between the severity of depressive symptoms and the results of the
      neuroendocrine tests. The combined use of both immunological and neuroendocrine
      tests did not add sensitivity to the immunological identification of depressed
      patients. Before and after treatment the immunoreactive vimentin filaments
      significantly increased (p < 0.01) after incubation of monocyte with naloxone.
      There was a significant correlation (p < 0.05) between the immune parameters
      studied in both phases of the study. CONCLUSIONS: The findings indicate that the
      monocyte dysfunction is temporally associated with the state of depression and
      lead us to consider the role of the monocyte parameters as sensitive depressive
      state markers, while the combined use of both neuroendocrine and immunological
      tests in current clinical practice would be debatable. On the other hand, as the
      cytoskeletal dysfunction was reversed with naloxone, our findings underline
      previous reports suggesting that an increased opioid activity could mediate
      monocyte dysfunction.

PMID- 7625240
TI  - [Pharmacological treatment of the intermittent explosive disorder. Report of
      three cases and literature review].
AB  - The treatment of intermittent explosive disorder is still empirical, although it
      tries to use drugs according to present knowledge on neurobiology of aggression.
      We report three patients in which a good control of aggressive behavior was
      achieved using inhibitors of serotonin reuptake and carbamazepine. We review the
      literature on pharmacologic treatment of aggressive behavior.

PMID- 7625241
TI  - [Subjective assessment tools in mental health].

PMID- 7625242
TI  - [A new eating disorder (diagnostic debate II)].
AB  - Binge Eating Disorder is a new eating disorder that describes the eating
      disturbance of some individuals who suffer from recurrent binge eating but who do
      not engage in the compensatory behaviors to avoid weight gain seen in bulimia
      Nervosa. Problems and advantages associated with the inclusion of Binge Eating
      Disorder in Criteria Sets and Axes Provided for Further Study (Appendix B) in DSM
      IV are reviewed.

PMID- 7625243
TI  - Effects of electro-acupuncture on C-FOS expression in gerbil hippocampus during
      transient global ischemia.
AB  - We studied the effects of electro-acupuncture (EA) on C-FOS expression as well as
      on the histological changes in various regions of hippocampus in the gerbil acute
      global ischemia model. EA was administered at points of 'Feng-fu' and 'Jin-suo'
      with a frequency of 7 Hz and an intensity of 6 mA for 30 minutes. EA can
      substantially potentiate the induction of C-FOS protein like immunoreactivity
      (CFPLI) in neurons of various regions in hippocampus following transient global
      ischemia, especially in the CA1 subfield. At the same time EA can prevent most of
      the CA1 cells from delayed degeneration after ischemia. These results indicate
      that EA has the protective effect on neurons of hippocampus after cerebral
      ischemia and C-FOS may be involved in this process.

PMID- 7625244
TI  - Involvement of the pineal body in the Bi-Digital O-Ring Test.
AB  - As an interesting exception to the general clinical application of the Bi-Digital
      O-Ring Test (BDORT), the test could not be performed successfully in diagnosing a
      patient who suffered from cancer of the pineal body. The following examinations
      were attempted using the BDORT: 1) The thymus representation area, 2) the distal
      forearm during compression of the upper arm, 3) surface representations of
      diseased areas that had previously been identified by the indirect method with
      slide preparations of pineal body or lung cancer tissue, 4) holding of oncogene c
      fos Ab2 and integrin alpha 5 beta 1. Results suggest that the failure of the
      BDORT might be due to the absence of pineal body function. It is suggested that
      the sensor for the BDORT might exist in the pineal body since 1) BDORT cannot be
      successfully performed when the eyes are closed, and the pineal body is sensitive
      to light; 2) electromagnetic resonance might stimulate this sensor; and 3) N
      acetyltransferase, the enzyme that converts serotonin to methylserotonin in the
      pineal body, might be inhibited by activation of this sensor. As a result,
      serotonin levels might be increased by activation of this sensor, which might
      then inhibit finger flexor muscle contraction needed to maintain an O-ring in
      BDORT.

PMID- 7625245
TI  - Acupuncture in the treatment of paralysis in chronic and acute stroke patients-
      improvement correlated with specific CT scan lesion sites.
AB  - A total of 20 stroke patients received acupuncture, including 10 chronic and 10
      acute patients; 19 of the 20 patients (95%) could be correctly classified
      regarding beneficial response to acupuncture, versus poor response, based on CT
      scan lesion site data, alone. Patients with beneficial response had damage to
      less than half of the motor pathway areas on CT scan, especially in the
      periventricular white matter area (PVWM) at the level of the body of the lateral
      ventricle. Overall, 8 of the 20 patients receiving acupuncture had beneficial
      response with measurable objective improvement in motor function, including 3 of
      the 10 chronic patients treated at > 3 months poststroke, and 5 of the 10 acute
      patients treated at < 3 months poststroke. Among the 8 patients with beneficial
      response, significant improvements were observed in knee flexion, knee extension,
      and shoulder abduction. Neither age, nor months poststroke when acupuncture was
      begun, was significantly correlated with the total number of improved tests, post
      acupuncture. Two chronic patients with beneficial response first began receiving
      acupuncture at 3 years and 6 years poststroke. Most improvements were sustained
      for at least 4 months after the last acupuncture treatment.

PMID- 7625246
TI  - New directions for research in prevention and treatment of delinquency: a review
      and proposal.
AB  - The past century has witnessed a number of approaches to the prevention and
      treatment of delinquency. Some approaches have emphasized physiological,
      psychological, and other individual characteristics; others have focused on the
      structure of the family; and still others have considered the structure of social
      relations within the broader society. More recent approaches have attempted to
      conceptualize an integrated complex of factors which includes community
      characteristics. This article reviews the various approaches which have dominated
      the field over the last few decades and concludes with a methodological proposal
      which may facilitate the systematic consideration of these various factors.

PMID- 7625247
TI  - The changing paradigm of community health: the role of school-based health
      centers.
AB  - This article examines the health care needs of adolescents and the barriers that
      keep young people from receiving services. The role of school-based health
      services in meeting the health care needs of adolescents is explored.

PMID- 7625248
TI  - Effects of economic hardship on adolescent self-esteem: a family mediation model.
AB  - The purpose of this study was to investigate the relationship between economic
      hardship, family relationships, and adolescent self-esteem in a sample of 387
      midwestern families. The results of LISREL analyses showed that economic hardship
      had an adverse effect on adolescent self-esteem, and that this effect was
      primarily mediated through the parent-adolescent relationship. The data also
      indicated that the marital relationship was negatively affected by economic
      hardship, but there was no direct relationship between parents' marital
      relationship and adolescents' self-esteem. The findings of this study are
      consistent with the theory that economic hardship reduces affective parental
      support and may thus convey a negative appraisal of the adolescent thereby
      lowering his or her self-esteem.

PMID- 7625250
TI  - Assessing adolescents' prosocial behavior: the Family Helping Inventory.
AB  - This study examined the structure and psychometric properties of a self-report
      measure of adolescents' helping behavior within the family--the Family Helping
      Inventory (FHI)--and of its two scales, the Sibling Helping Scale (SHS) and the
      Parent Helping Scale (PHS). The FHI was administered to 202 adolescents along
      with several existing measures of prosocial tendencies and with a measure of
      Machiavellianism. Factor analyses yielded four internally consistent subscales
      for the SHS and five for the PHS, all of which were conceptually related to
      inventories reflecting family support among adults. Both convergent and
      discriminant validity were demonstrated as well.

PMID- 7625249
TI  - Adolescents' intimacy with parents and friends.
AB  - Adolescents' perceived levels of intimacy with their mother, father, and close
      friend were examined as a function of demographic, family and school, and
      psychological variables. Students with same-sex friends and greater interest in
      school reported greater intimacy with their mothers. Students with higher self
      esteem, lower depression, and lower risk-taking scores reported greater intimacy
      with their mothers and fathers. The greatest number of relationships with
      positive variables involved intimacy with mothers.

PMID- 7625251
TI  - Family environments of adolescent sex offenders and other juvenile delinquents.
AB  - This study compared the family environments of adolescent sex offenders and
      violent and nonviolent juvenile delinquents with a normative sample of
      adolescents. Differences between the juvenile delinquents and the normative
      sample were found on six of the ten subscales of the Family Environment Scale
      (i.e., cohesion, expressiveness, independence, intellectual-cultural orientation,
      active-recreational orientation, and control). No differences were found on four
      variables (i.e., conflict, achievement orientation, moral-religious emphasis, and
      organization). No differences were found among the three categories of juvenile
      delinquents. Implications of the findings for clinical intervention and further
      research are offered.

PMID- 7625252
TI  - Eating behavior in junior high school females.
AB  - Female junior high school students (N = 175) were surveyed in an effort to
      ascertain present eating behavior as well as attitudes regarding dieting and
      concern about body weight. It was found that many subjects appear to have
      concerns as early as elementary school. Limitations of these findings are
      discussed as well as implications for further research.

PMID- 7625253
TI  - Relationships of parents' perceived actions toward their children.
AB  - Research has generally supported the view that parents' attitudes and practices
      predispose children to act in certain ways. Bell (1968), however, proposed an
      alternate theory which suggested that children and adolescents often mold the way
      their parents act. Parish (1980) subsequently reported support for Bell's
      position in that parents were, indeed, found to parent like one another, possibly
      in response to their children's actions. The present study sought to further
      examine the Bell (1968) theory by seeking to determine if parents are consistent
      with each other or with themselves in their parenting attitudes and practices.
      Parents were perceived to act like one another (at least to a moderately
      significant degree), but fathers were much more likely to parent in particular
      ways (i.e., if they were restrictive they were also more likely to be warm, or if
      they were permissive they were also more likely to be hostile), independent of
      how their wives were perceived to act. The implications of these findings are
      discussed.

PMID- 7625254
TI  - Young adult reactions to death in literature and life.
AB  - The death of a loved one can have a profound, permanent effect on young adults.
      Their confusion over isolation and intimacy issues, which normally begins in
      adolescence, complicates their grief. Adults can ease the stress of the grieving
      process and lessen long-term, negative effects by providing emotional support and
      a sense of connectedness. This article seeks to understand young adult reactions
      through their literature and suggests healing responses early in bereavement.
      Examples of typical behavior such as resistance to authority, withdrawal, and
      hiding feelings are taken from young adult fiction and nonfiction available from
      public and school libraries.

PMID- 7625255
TI  - The relative effectiveness of a peer-led and adult-led smoking intervention
      program.
AB  - This study compared a six-session peer-led smoking intervention program for high
      school-age youth to the same program led by adults. Ninety-three students
      participated in the study and were divided into peer-led, adult-led, and control
      groups. Number of cigarettes smoked was assessed by self-report through pretest,
      posttest and one-month follow-up measures. Self-efficacy was measured post-and
      follow-up. Student feedback regarding the helpfulness of program components was
      also assessed. There was a significant difference in the number of cigarettes
      smoked by students in both peer-led and adult-led groups when compared to the
      control group (p = .0001). Smoking reduction continued to take place in both
      treatment groups at the one-month follow-up measure. Those students who were
      exposed to fewer smoking individuals in their daily lives were able to maintain a
      reduction in smoking when measured one month after completion of the program.

PMID- 7625256
TI  - Talking with juvenile offenders about gay males and lesbians: implications for
      combating homophobia.
AB  - Violence against gay males and lesbians, much of it perpetrated by young people,
      has emerged as a significant social problem. Thirty-one juvenile offenders were
      asked a series of structured questions in order to elucidate the functions their
      attitudes toward homosexuals serve. In addition, responses were examined for
      evidence of social-structural and cognitive variables which mediate offending
      behaviors. Juvenile offenders were found to hold attitudes toward homosexuals
      characterized by negativity, ambivalence, and defensiveness. These attitudes were
      maintained by particular myths and stereotypes about gay and lesbian culture, and
      were related to Opportunism, Impulsivity, Role-Taking Inability, and Disabilities
      in Social Problem Solving. Specific recommendations for combating homophobic
      attitudes and behaviors in juvenile offender populations are discussed.

PMID- 7625257
TI  - A Teen Hot Line.
AB  - This article deals with the development and implementation of a Teen Hot Line
      that utilizes skilled student volunteers. A comprehensive and meaningful training
      program combined with a high level of acceptance among the general youth
      population has resulted in a valuable service for both the client callers and the
      student volunteers.

PMID- 7625258
TI  - Risk factors leading to adolescent substance abuse.
AB  - The risk factors leading to adolescent substance abuse were examined to provide
      greater understanding of their influence. The risk factors were divided into four
      major categories: demographic, social, behavioral, and individual. Each category
      was broken down into its respective components, among which are ages of
      susceptibility; gender differences; the influences of family, peers, and
      environment; the influence of past use of substances; the relationship between
      substance abuse and other problem behaviors; and the relationships between
      substance abuse and academic achievement, psychological variables, and student
      employment. Background information on the prevalence of adolescent substance
      abuse is also provided.

PMID- 7625259
TI  - Violent behaviors among African-American adolescents.
AB  - Since the beginning of the 1980s, many urban cities in the U.S. have witnessed an
      increase in violent behaviors among African-American adolescents, and this trend
      appears to be gaining momentum. This paper examines Erik Erikson's developmental
      stage of identity versus identity diffusion and its relationship to African
      American adolescents' behavior. In addition, other factors are examined which may
      be contributing to this phenomenon, and suggestions are offered for therapeutic
      treatment of this population.

PMID- 7625260
TI  - There's a first time for everything: understanding adolescence.
AB  - Adolescence has been regarded as a stormy, emotionally turbulent time by many.
      Some have blamed physiological factors; others have pointed to peer pressure and
      intimacy. This paper examines the phenomenon of the "first time"--the teenagers
      first date, first job, first sexual experience. Since these "firsts" are embued
      with an inordinate amount of emotional investment, they offer an alternative
      understanding for the "storm and stress"--the emotional underpinnings of
      adolescence.

PMID- 7625261
TI  - The role of socioeconomic status in adolescent literature.
AB  - This article attempts to establish that socioeconomic status (SES) plays an
      important role in the lives of adolescents and is reflected in adolescent
      literature. The emphasis on SES in four adolescent novels: The Outsiders by S.E.
      Hinton, To Kill a Mockingbird by Harper Lee, The Catcher in the Rye by J. D.
      Salinger, and The Pigman by Paul Zindel suggests that both the authors and their
      young readers are aware of its influence in today's society. Three areas which
      are greatly affected by SES are examined: adolescents' self-esteem, how it
      affects characterization and subsequently the degree to which adolescents
      identify with a literary character, and how it functions as a learning device,
      enabling authors to infuse their own moral values into the minds of their
      audiences.

PMID- 7625262
TI  - A study of underlying variables affecting aspirations of rural adolescents.
AB  - Aspirations are comprised of two major components--inspiration and ambition.
      Ambitions represents the ability to look ahead and invest in the future.
      Inspiration can be described as the ability to invest the time, energy, and
      effort to reach those ambitions. Variables such as how and why students spend
      their time illustrate the dynamics of these two components. The data in this
      report are based on the responses to the Aspirations Survey of 2,677 eighth- to
      twelfth-grade students from seven rural schools in Maine. The data suggest that
      many students have no understanding of why they engage in certain activities. If
      students are to be responsible for their education and more importantly for
      themselves, they must see purpose in their pursuits.

PMID- 7625263
TI  - Change in maternal depressive mood: unique contributions to adolescent
      functioning over time.
AB  - There is substantial evidence of the relationship between maternal depressive
      mood and problematic child functioning. The vast majority of studies in this area
      concentrate on cross-sectional designs and depressive mood at one point in time.
      In contrast to the existing literature, the goal of this study was to investigate
      the relation of change in maternal depressed mood across time and adolescent
      functioning, including the possible moderating effects of gender of the
      adolescent and the marital status of parents. Regression analyses indicated that
      increased depressed mood across one year predicted teacher report of higher
      levels of externalizing and internalizing problems and lower levels of social
      competence, above that which could be predicted from the initial assessment of
      depressed mood. With one exception, neither gender nor parental marital status
      qualified the findings. The results suggest that static levels of maternal
      depressive mood are not sufficient for forecasting adolescent functioning. Future
      research needs also to consider change in such mood.

PMID- 7625264
TI  - Movie portrayals of juvenile delinquency: Part 1--Epidemiology and criminology.
AB  - Movies chronicling the phenomenology of juvenile delinquency have been produced
      since the 1930s. These films have become part of American culture and are at once
      a representation of and possible etiologic factor in causing delinquency. This
      paper reviews aspects of the epidemiology and criminology of delinquency and how
      they have been reflected in American films. Movies of historical and
      sociopsychological significance are examined in more detail, and the following
      questions are addressed: As the ethnicity of the United States changes, to what
      extent are American films dealing with juvenile delinquency reflecting this
      evolution? How are such films symbolizing the theme of "law and order," pervasive
      in U.S. approaches to crime for a quarter century? When these movies come close
      to mimicking certain aspects of the environment of the viewer, an interactive or
      "resonating" effect may occur such that the youth who view such films may be more
      likely to commit delinquent acts. A countervailing utility of these movies may be
      their prosocial potential in educating and rehabilitating youth.

PMID- 7625265
TI  - Reproductive and contraceptive knowledge, contraceptive self-efficacy, and
      contraceptive behavior among teenage women.
AB  - This research utilizes a social learning theory perspective to investigate the
      relationships among teenage women's Contraceptive Self-Efficacy (CSE),
      reproductive and contraceptive knowledge (RCK), and contraceptive behavior. It
      was posited that CSE might influence the way knowledge translates into behavior
      because individuals who feel they can and should use contraceptives may be more
      receptive to information. A secondary line of analysis examined the individual
      responses on the RCK to ascertain common knowledge and myths. The 521 respondents
      were from two diverse samples of teenage women attending family planning clinics.
      Although no significant relationships were found between RCK and behavior, the
      four-factor model of CSE explained 12% and 28% of the variance in RCK in the two
      samples. Results on the RCK items revealed sample differences and common areas of
      misinformation that are critical to effective contraceptive and prophylactic use.
      The findings are used to identify measurement issues that may account for the
      inconsistent findings regarding the relationship between RCK and behavior, and to
      recommend content for educational interventions.

PMID- 7625266
TI  - A case of family dysfunction and teenage suicide attempt: applicability of a
      family systems paradigm.
AB  - A large body of research indicates that suicidal behavior in adolescence is
      related to dysfunctional family processes. The purpose of this paper was to
      investigate this relationship focusing on the concepts of boundary transgression,
      double bind interactions, and the demarcation of kinship roles in the family. The
      possibility is explored that suicidal behavior is a double bind response to
      contradictions in the way roles and responsibilities are distributed in the
      family, and that as a response, suicide attempts may contain a simultaneous
      appeal for help and an assertion of independence from the family. A case vignette
      is presented to illustrate these processes.

PMID- 7625267
TI  - Differences in adolescent self-concept as a function of race, geographic
      location, and pregnancy.
AB  - This study compares the self-concept scores of pregnant African-American
      adolescents from urban and rural areas. It was conducted in alternative schools
      for pregnant adolescents using the Offer Self-Image Questionnaire (OSIQ) as a
      data collection instrument with 199 girls 13 to 19 years of age. It was
      hypothesized that the self-concept of pregnant, African-American adolescents
      would not be influenced by their age or geographic location. Results of the data
      analysis refuted the null hypotheses. The self-concept scores of both groups were
      not as high as those of a nonpregnant norm group of adolescents, but the scores
      of the pregnant adolescents were very similar regardless of age or geographic
      location.

PMID- 7625268
TI  - Meiosis specific transcription and functional proteins.
AB  - We have discussed and/or demonstrated the following: 1. Many enzymes and
      structural proteins have been identified as meiosis-specific proteins. These can
      be classified according to their metabolic behavior. 2. We obtained and analyzed
      18 cDNA clones from lily meiocytes. One of them, LIM15, was similar to known
      genes like RecA, RAD57, and DMC1/ISC2, and might function in pairing and
      recombination. 3. Transcription of these genes is regulated by their regulator
      region(s). When such a regulator, mei2 promoter sequence isolated from S. pombe,
      was ligated with the proper vector and transfected, it functioned specifically in
      meiotic cells but not in the somatic cells tested. 4. Presence of a new lamin,
      lamin B3 was identified in mammalian spermatocytes and the transfection of lamin
      B3 gene (inserted into vector) into somatic cells alters the nuclear shape,
      possibly expressing a characteristic shape of meiotic nuclei. Lamin B3 was
      synthesized after meiosis-specific processing of lamin B2 mRNA. Other protein
      specific to meiotic nuclear-skeleton (MNS1) were found and characterized. All
      these events were studied basically focussing on homologous pairing and
      recombination which take place in meiosis I. We recognize the necessity of
      further studies on these and other events like the structure and segregation of
      chromosomes and the suppression of somatic gene expression during meiosis.

PMID- 7625269
TI  - Hotspots of homologous recombination in mouse meiosis.
AB  - The molecular mapping of recombinational breakpoints in the proximal region of
      the mouse MHC has revealed four hotspots at which breakpoints are clustered. A
      direct comparison of the nucleotide sequences of two independent hotspots
      revealed common molecular elements: a consensus sequence of the middle-repetitive
      MT-family, a repeat of tetramer sequences and a sequence homologous to a solitary
      LTR of mouse retroviruses. Extremely high frequency of recombination is observed
      at these hotspots when particular MHC haplotypes are used in genetic crosses.
      Wild mouse-derived wm7 haplotype instigates recombination at the hotspot located
      at the 3'-end of the Lmp-2 gene only during female meiosis. Fine genetic analysis
      demonstrated that the wm7 haplotype carries a genetic factor to instigate
      recombination and another factor to suppress recombination specifically during
      male meiosis. In addition, there is no dose effect of the hotspot on frequency of
      recombination. Finally, we described an attempt to establish an efficient in
      vitro assay system for monitoring recombination using plasmid DNAs that contain
      the Lmp-2 hotspot and nuclear extracts prepared from mouse testis.

PMID- 7625270
TI  - A new type of E. coli recombinational hotspot which requires for activity both
      DNA replication termination events and the Chi sequence.
AB  - In E. coli rnh- mutants we identified chromosome-derived, specific DNA fragments
      termed Hot DNA. When the DNA in the ccc form is integrated into the E. coli
      genome by homologous recombination to form a directly repeated structure, a
      striking enhancement of excisional recombination between the repeats occurs. We
      obtained 8 groups of such Hot DNA, 7 of which were clustered in a narrow region
      called the replication terminus region (about 280 kb) on the circular E. coli
      genome. A Ter site can impede the replication fork in a polar fashion. The six
      Ter sites are approximately symmetrical in the terminus and surrounding region.
      To block the fork at the Ter site, a protein factor, Ter binding protein encoded
      in the tau (or tus) gene, is required. In tau- cells, Hot activity of HotA, B,
      and C DNAs disappears, thereby indicating that the Hot activity is fork arrest
      dependent. Other Hot activities were tau-independent. In addition, for at least
      HotA activity, the presence of Chi, and E. coli recombinational hotspot sequence,
      is required; the Chi dependent HotA activity was detected in a wild type strain
      but to a lesser extent than that in the rnh- mutant. To explain the HotA
      phenomenon at the molecular level, we propose a model in which a ds-break occurs
      at the replication fork arrested at the Ter site. Our recent data that HOT1, a
      yeast recombinational hotspot, may also depend on the fork blocking event for
      activity, suggests that a similar ds-break occurs in both eucaryotes and
      procaryotes.

PMID- 7625271
TI  - A differential cloning procedure for rearranged or altered genomic DNA based on
      in-gel competitive reassociation.
AB  - We have developed a substantially improved differential cloning procedure
      designed for cloning anonymous altered restriction DNA fragments from higher
      organisms. The improvements include (i) in-gel dissociation and reassociation of
      biotinylated restriction digests of target DNA fragments, (ii) replacement of
      agarose gel by a synthetic gel material for electrophoresis, (iii) use of a
      reassociation enhancing reagent (CTAB) for in-gel reassociation, and (iv)
      introduction of PCR. After several cycles of IGCR, we attained considerable
      enrichment of altered or rearranged DNA fragments which were originally present
      at one copy or less per complex eukaryotic genome. Examples of enrichment include
      those of an exogenously added DNA fragment, a chromosomal DNA sequence that has
      undergone a deletion, and DNA fragments containing a recombination junction.

PMID- 7625272
TI  - V(D)J recombination of immunoglobulin genes.
AB  - We have constructed transgenic mice carrying an artificial substrate of V(D)J
      recombination. In this substrate, the only DNA fragments derived from Ig genes
      were short stretches of recombination signal sequences. This artificial substrate
      was rearranged at high frequency in lymphocytes, although in non-lymphoid cells
      no rearrangement was detected even by a sensitive PCR assay. This result
      indicates that the V(D)J recombination requires only the signal sequences and
      that a recombination similar to the V(D)J recombination does not occur in non
      lymphoid tissues including the central nervous tissue. A protein binding to the
      V(D)J recombination signals was purified and its cDNA was cloned. This protein,
      termed RBP-J kappa, was initially considered to be involved in V(D)J
      recombination because of its DNA binding specificity and structural similarity to
      site-specific recombinases known as the integrase family. However, further study
      on the Drosophila homolog of RBP-J kappa indicated that RBP-J kappa probably
      functions as a transcription factor in the differentiation of the peripheral
      nervous tissues. The exact function of RBP-J kappa is still unknown. Analogous to
      the Drosophila gene, it is suggested that mouse RBP-J kappa participates in the
      regulation of differentiation of various tissues.

PMID- 7625273
TI  - Mating variation by DNA inversions of shufflon in plasmid R64.
AB  - Gene organization of the 54-kb transfer region of IncI1 plasmid R64 was deduced
      from the DNA sequence. Forty-eight ORFs were found in this region. A unique DNA
      rearrangement designated shufflon is located at the downstream region of an
      operon responsible for synthesis of thin pilus. The shufflon of R64 consists of
      four DNA segments, designated as A, B, C, and D, which are flanked and separated
      by seven 19-bp repeat sequences. Site-specific recombination mediated by the
      product of the rci gene between any two inverted repeats results in a complex DNA
      rearrangement. An analysis of open reading frames revealed that the shufflon is a
      biological switch to select one of seven C-terminal segments of the pilV genes.
      The products of pilV genes were shown to be components of thin pilus which was
      required for liquid mating. Seven R64 derivatives where the pilV genes were fixed
      in the seven C-terminal segments were constructed and their transfer frequencies
      in liquid mating were measured using various bacterial strains as recipients.
      Transfer frequencies of R64 in liquid mating strongly depended on the combination
      of C-terminal segments of the pilV genes in donor cells and bacterial strains of
      recipient cells, suggesting that the shufflon determines the recipient
      specificity in liquid mating of plasmid R64.

PMID- 7625274
TI  - A novel assay for illegitimate recombination in Escherichia coli: stimulation of
      lambda bio transducing phage formation by ultra-violet light and its independence
      from RecA function.
AB  - We developed a novel assay system for illegitimate recombination, in which the
      frequency of the formation of lambda Spi- phages formed during prophage induction
      was measured with an E. coli P2 lysogen as the indicator bacteria. Since almost
      all of the lambda Spi- phages thus detected contain attR, they have essentially
      the same structures as lambda bio transducing phages, indicating that this assay
      system enables us to detect specialized transducing phages that produce
      heterogenote transductants, thus ignoring the occurrences of docL and docR
      particles which carry only one cohesive end. The following results on the
      formation of specialized transducing phages have been obtained by this assay
      system to date. (1) Irradiation with UV light greatly enhanced the formation of
      lambda Spi- phages. (2) Treatments with other DNA-damaging agents also enhanced
      the formation of lambda Spi- phages. (3) Illegitimate recombination during
      prophage induction does not require the RecA function, indicating that
      enhancement of lambda Spi- phage formation is not controlled by the SOS
      regulatory system. (4) Preliminary results suggested that DNA gyrase is involved
      in the formation of lambda Spi- phage during pro-phage induction. Since the above
      results were consistent with most of the previous observations on the
      illegitimate recombination in other systems, the Spi- assay system can provide
      important clues to the mechanism of illegitimate recombination.

PMID- 7625275
TI  - IS1-encoded proteins, InsA and the InsA-B'-InsB transframe protein (transposase):
      functions deduced from their DNA-binding ability.
AB  - Insertion sequence IS1 encodes a transframe protein, InsA-B'-InsB, which is
      produced from two out-of-phase reading frames, insA and B'-insB, by translational
      frameshifting at a run of adenines. Unless the frameshifting event occurs, the
      InsA protein is produced from IS1. We found that cells harboring a plasmid
      carrying an IS1 mutant with a single adenine insertion in the run of adenines
      contained miniplasmids. Cloning and DNA sequencing analyses of the miniplasmids
      revealed that they had a deletion extending from an inverted repeat (IR) at the
      left end of IS1. This indicates that they were generated by IS1-mediated deletion
      due to efficient production of the InsA-B'-InsB transframe protein that is IS1
      transposase. Both the InsA protein and transposase were partially purified as a
      fusion protein with collagen-LacZ by LacZ-specific affinity column
      chromatography. The InsA* and the collagenolyzed InsA* were found to bind
      specifically to a 24-bp region within each of the IRs at the ends of IS1. The
      transposase Tnp* and the collagenolyzed Tnp* were found to bind to the sequence
      with or without IR, but preferentially to that with IR. The nonspecific DNA
      binding ability of transposase may be involved in recognition of the target DNA,
      an important process of transposition of IS1. Both InsA and transposase have the
      IR-specific DNA binding ability and a common polypeptide segment containing the
      alpha-helix-turn-alpha-helix motif, supporting the previous indication that InsA
      competes with transposase to bind to IRs and thus becomes a transposition
      inhibitor. Based on the observations described in this article, we speculate that
      transposase of IS1 consists of at least two domains, the N-terminal half, which
      almost entirely overlaps InsA, and the C-terminal half, which almost entirely
      overlaps B'-InsB. The frameshifting event adds the latter domain to the former to
      give the transposase activity recognizing IRs and the target sequence to initiate
      the transposition reaction.

PMID- 7625276
TI  - Analysis of the DNA binding site of Escherichia coli RecA protein.
AB  - To investigate the DNA binding site of RecA protein, we constructed 15 recA
      mutants having alterations in the regions homologous to the other ssDNA binding
      proteins. The in vivo analyses showed that the mutational change at Arg243,
      Lys248, Tyr264, or simultaneously at Lys6 and Lys19, or Lys6 and Lys23 caused
      severe defects in the recA functions, while other mutational changes did not.
      Purified RecA-K6A-K23A (Lys6 and Lys23 changed to Ala and Ala, respectively)
      protein was indistinguishable from the wild-type RecA protein in its binding to
      DNA. However, the RecA-R243A (Arg243 changed to Ala) and RecA-Y264A (Tyr264
      changed to Ala) proteins were defective in binding to both ss- and ds-DNA. In
      self-oligomerization property, RecA-R243A was proficient but RecA-Y264A was
      deficient, suggesting that the RecA-R243A protein had a defect in DNA binding
      site and the RecA-Y264A protein was defective in its interaction with the
      adjacent RecA molecule. The region of residues 243-257 including the Arg243 is
      highly homologous to the DNA binding motif in the ssDNA binding proteins, while
      the eukaryotic RecA homologues have a similar structure at the amino-terminal
      side proximal to the nucleotide binding core. The region of residues 243-257
      would be a part of the DNA binding site. The other parts of this site would be
      the Tyr103 and the region of residues 178-183, which were cross-linked to ssDNA.
      These three regions lie in a line in the crystal structure.

PMID- 7625277
TI  - Recombination apparatus of T4 phage.
AB  - The substantial process of general DNA recombination consists of production of
      ssDNA, exchange of the ssDNA and its homologous strand in a duplex, and cleavage
      of branched DNA to maturate recombination intermediates. Ten genes of T4 phage
      are involved in general recombination and apparently encode all of the proteins
      required for its own recombination. Several proteins among them interact with
      each other in a highly specific manner based on a protein-protein affinity and
      constitute a multicomponent protein machine to create an ssDNA gap essential for
      production of recombinogenic ssDNA, a machine to supply recombinogenic ssDNA
      which has a free end, or a machine to transfer the recombinogenic single strand
      into a homologous duplex.

PMID- 7625278
TI  - Molecular mechanisms of Holliday junction processing in Escherichia coli.
AB  - Recent genetic and biochemical studies revealed the mechanisms of late stage of
      homologous recombination in E. coli. A central intermediate of recombination
      called "Holliday structure", in which two homologous duplex DNA molecules are
      linked by a single-stranded crossover, is formed by the functions of RecA and
      several other proteins. The products of the ruvA and ruvB genes, which constitute
      an SOS regulated operon, form a functional complex that promotes migration of
      Holliday junctions by catalyzing strand exchange reaction, thus enlarging the
      heteroduplex region. RuvA is a DNA-binding protein specific for these junctions,
      and RuvB is a motor molecule for branch migration providing energy by hydrolyzing
      ATP. The product of the ruvC gene, which is not regulated by the SOS system,
      resolves Holiday junctions by introducing nicks at or near the crossover junction
      in strands with the same polarity at the same sites. The recombination reaction
      is completed by sealing the nicks with DNA ligase, resulting in spliced or
      patched recombinants. The product of the recG gene provides an alternative route
      for resolving Holliday junctions. RecG has been proposed to promote branch
      migration in the opposite direction to that promoted by RecA protein. The atomic
      structure of RuvC protein revealed by crystallographic study, when combined with
      mutational analysis of RuvC, provides mechanistic insights into the interactions
      of RuvC with Holliday junction.

PMID- 7625280
TI  - Multi-site-specific endonucleases and the initiation of homologous genetic
      recombination in yeast.
AB  - The notion that homologous recombination is a regulated biological process is not
      a familiar one. In yeasts, homologous recombination and most site-specific ones
      are initiated by site-specific double-stranded breaks that are introduced within
      cis-acting elements for the recombination. On the other hand, yeasts have a group
      of site-specific endonucleases (multi-site-specific endonucleases) that have a
      number of cleavage sites on each DNA. One of them, Endo.SceI of S. cerevisiae,
      was shown to introduce double-stranded breaks at a number of well-defined sites
      on the mitochondrial DNA in vivo. An Endo.SceI-induced double-stranded break was
      demonstrated to induce homologous recombination in mitochondria. Like the case of
      homologous recombination of nuclear chromosomes, the double-stranded break
      induces gene conversion of both genetic markers flanking and in the proximity of
      the cleavage site, and the cleaved DNA acts as a recipient of genetic information
      from the uncleaved partner DNA. The 70 kDa-heat-shock protein (HSP70)-subunit of
      Endo.SceI and a general role of the HSP70 in the regulation of protein-folding
      suggest the regulation of nucleolytic activity of Endo.SceI.

PMID- 7625279
TI  - Functions of the yeast meiotic recombination genes, MRE11 and MRE2.
AB  - Mutants defective in meiotic recombination were isolated using a disomic haploid
      strain of S. cerevisiae, and were classified into 11 genes. Two, MRE2 and MRE11,
      are new genes and nine are previously identified genes. The mre2 and mre11
      deletion mutants are proficient in mitotic recombination, but are defective in
      meiotic recombination and in formation of viable spores. The spore inviability,
      however, is alleviated by an additional mutation, spo13, which bypasses meiosis
      I. In addition, neither meiosis specific DSBs at recombination hot-spots nor
      formation of synaptonemal complex occur in either mutant. Therefore, these two
      genes are involved in the formation of DSBs in meiotic recombination. While a
      temperature sensitive mre11-1 mutant is able to form DSBs at a permissive
      temperature, the formed DSBs are unable to resect at non permissive temperature.
      Therefore, the MRE11 gene is also involved in some step of the repair process
      after the DSB formation. Analysis of properties of the mre11 disruption mutant as
      well as the xrs2 mutant showed a similarity to those of the rad50 disruptant. We
      found that the mre11 disruption mutation is epistatic to rad50S mutation, as the
      xrs2 deletion mutation is epistatic to rad50S with regard to DSBs. Therefore,
      these three genes form an epistatic group. Interaction of the Mre11 protein with
      the Rad50 and the Xrs2 protein as well as alone was shown in vivo using the two
      hybrid system. The MRE2 gene encodes a protein containing two sets of RRM.
      Deficiency of recombination in a mre2 mutant that has an amino acid substitution
      in the N-terminal RRM can be suppressed by the MER2 gene on the multicopy
      plasmid. Further analysis showed that the Mre2 protein is involved in meiosis
      specific splicing of the MER2 transcripts in cooperation with the Mer1 protein.
      In conclusion, MRE genes are involved in the initiation of meiotic recombination
      through the formation of DSBs at recombination hot-spots in S. cerevisiae.

PMID- 7625282
TI  - Intestinal absorption of colostral lymphocytes in newborn lambs and their role in
      the development of immune status.
AB  - Two model experiments were conducted to study the intestinal absorption of
      colostral lymphoid cells and the role of these cells in the development of immune
      status in newborn lambs. In experiment I, 17 lambs of 14 Merino ewes were used.
      Suspensions of lymphoid cells separated from the colostrum (cell density: 5 x
      10(6)/ml) and blood (3 x 10(6)/ml) were labelled with technetium (Na99mTcO4) of
      37 MBq/ml radioactive concentration. In three groups of lambs, 10-ml volumes of
      the cell suspensions were injected directly into the duodenum after laparotomy,
      while in a fourth group (group Ia) the same volume was administered to the
      animals through an oesophageal tube. The labelled cells revealed that colostral
      cells of the lamb's own dam are absorbed from the gastrointestinal tract and get
      into the newborn lamb's lymph circulation irrespective of the route of
      application. In experiment II, involving 40 lambs of 40 ewes, we studied the
      effect of absorbed colostral lymphocytes on the development of the newborn lamb's
      immune status. Twenty ewes (group A) each were treated with 3 ml tetanus anatoxin
      twice, while the remaining animals (group B) were left uninoculated. Lambs of
      group A (designated A2) were separated from their dams immediately after birth,
      then were administered, through an oesophageal tube, 10 ml of a suspension of
      lymphoid cells (cell density: 5 x 10(6)/ml) separated from the maternal
      colostrum. Subsequently, the lambs were interchanged with lambs of nonimmunized
      ewes of group B (designated lambs B1), i.e. were mutually put out to nursing. At
      three days of age, lambs of groups A1, A2, B1 and B2 were inoculated with 3 ml
      tetanus anatoxin, then blood samples were taken from them 5 times in a period of
      27 days for comparative examination of the humoral and cellular immune reactions.
      The results demonstrate that lymphoid cells from the colostrum of the lambs' own
      dam become absorbed into the newborn lambs' lymph circulation, remain
      immunologically active and may transfer, besides immunological memory, also
      cellular activity.

PMID- 7625281
TI  - A species-specific interaction of rad51 and rad52 proteins in eukaryotes.
AB  - The structures and properties of the Rad51 and Rad52 proteins in eukaryotes are
      described. Both proteins form a complex and are responsible for recombination and
      repair reactions. The N-terminal region of the Rad51 protein interacts with the C
      terminal region of the Rad52 protein. Species-specific interaction is probably
      essential for the functioning of these genes.

PMID- 7625283
TI  - Contamination of broiler chicken's mash and litter with moulds, aflatoxins,
      ochratoxin A and zearalenone.
AB  - Contamination of broiler chicken's mash and litter with moulds, aflatoxin B1
      (AB1), G1 (AG1), ochratoxin A (OA) and zearalenone (F-2 toxin) was examined on a
      broiler fattening farm. All broiler chicken's mash samples tested were
      contaminated with moulds. The highest total viable counts of moulds (3.3 x 10(5)
      per g) were found in broiler starter diet. Moulds isolated from mash were
      classified into 8 genera and 27 species. Many of them (Aspergillus spp., Fusarium
      spp., Penicillium spp.) are known as mycotoxin-producing moulds. Fusarium
      moniliforme was the dominant species in mash mycopopulations. Moulds were also
      found in all litter samples. The highest fungus count (80 x 10(5) per g) in
      litter was found at the beginning of fattening. Fungi isolated from litter
      samples belonged to 9 genera and 22 species. Aspergillus, Penicillium and Mucor
      were the most prevalent genera. None of the broiler chicken's mash and litter
      samples tested was contaminated either with AB1, AG1, OA or with F-2 toxin. F.
      moniliforme was zearalenone-negative also under laboratory conditions.

PMID- 7625284
TI  - Histological changes in the swimbladder wall of eels due to abnormal location of
      adults and second stage larvae of Anguillicola crassus.
AB  - In severe Anguillicola crassus infection of eels, adult helminths and 2nd stage
      larvae staying in the swimbladder lumen may occasionally get, through minor
      lesions of the tunica interna, into the subserosa of the swimbladder wall where
      they die and disintegrate. A thin connective tissue capsule is formed around the
      helminths that behave as foreign bodies in intercellular location, while the
      lacunas of the surrounding loose connective tissue comprise melanin-containing
      macrophages. In the environment of the 2nd stage larvae the formation of giant
      cells is a typical finding.

PMID- 7625286
TI  - Eosinophils in lymph nodes of cows infected by bovine leukaemia virus.
AB  - Prescapular lymph nodes from 109 animals positive to bovine leukaemia virus (BLV)
      were evaluated in this study. Lymph nodes of 81 animals (74.3%) showed an
      increased number of eosinophils (Eo) in a variety of pathological reactions. Eo
      counts in T-zonal hyperplasia (47 cases, 43.1%) and mixed hyperplasia (13 cases,
      11.9%) were significantly higher (P < 0.05 and P < 0.01, respectively) than in
      the control group. Similarly, a significantly increased number of blood
      eosinophils (BEo) was observed in cows with diffuse infiltration by Eo in the
      lymph nodes as compared to the number of BEo in cows serologically positive to
      BLV but without morphological changes in the lymph nodes and in cows which were
      serologically negative (P < 0.05 and P < 0.01, respectively). The possible role
      of eosinophilic granulocytes in the regulation of immune response to enzootic
      bovine leukaemia (EBL) is discussed.

PMID- 7625285
TI  - Ultrastructural observations on the third-generation merozoites of Eimeria
      tenella in chicks.
AB  - The fine structure of the third-generation merozoites of Eimeria tenella is
      described from caecal enterocytes of chicks 120 h after experimental infections.
      The merozoites conformed to the general eimerian pattern except that they were
      bounded by two unit membranes. Young gamonts also conformed to the general
      eimerian pattern, and were limited by an outer unit membrane and an interrupted
      inner membrane. Enterocytes invaded by third-generation merozoites showed a loss
      of microvilli and large blebs that protruded into the caecal lumen. These blebs
      appeared to contain only cytoplasm and not any cell organelles.

PMID- 7625287
TI  - Effect of mercury on the seminiferous epithelium of the fowl testis.
AB  - Phenylmercuric chloride was applied in three doses (5 ppm, 30 ppm Hg, and 30 ppm
      Hg + 4 ppm Se) via the food for 60 days. The effect of Hg with an without Se was
      studied histologically and the data of a shortened spermatogram were evaluated.
      Treatment with 30 ppm Hg resulted in hypospermia, occurrence of abnormally
      maturing spermatozoa, reduction of the volume of semen, and decrease in the
      number of spermatozoa. The dose of 5 ppm Hg only resulted in the appearance of
      abnormally developing cells and decreased sperm motility. The addition of Se
      maintained spermatogenesis and the values of semen on the control level.

PMID- 7625288
TI  - Variations in the milk yield and milk composition of dairy cows during lactation.
AB  - Variations in the milk yield and milk composition of a dairy cow colony (n = 23)
      were analyzed during 11 months of lactation. Milk yield followed a characteristic
      decreasing pattern in negative correlations with solid components (milk protein,
      lactose, total solids, milk fat). Titrable acidity (degree SH) was significantly
      (p < 0.1) higher in the milk of fresh-milking cows and it correlated negatively
      with lactose and positively with milk protein, milk fat and total solids. The
      concentrations of Zn, Fe and Cu tended to decrease, while Mn showed insignificant
      variation during lactation. Milk vitamin A showed a significant positive whilst
      milk vitamin E had a negative correlation with milk fat.

PMID- 7625289
TI  - Effect of severe energy restriction and refeeding on thyroid hormones in bulls.
AB  - Fifty-three Holstein-Friesian breeding bulls (944.99 +/- 14.59 kg) were fasted
      for 4 weeks. The influence of feeding on thyroid hormones was studied by
      comparing a starting point with a 4-week fasting period and a refeeding period.
      Blood samples were taken via a jugular vein catheter at 8:00 a.m. one day before,
      then once every week during, and two times after the fasting period. Plasma
      thyroxine (T4) and triiodothyronine (T3) levels were determined by direct
      radioimmuno-assay. The concentration of T4 and T3 decreased during fasting. The
      concentration of T3 increased after refeeding, but that of T4 did not. These data
      suggest that fasting is associated with a decrease in the peripheral conversion
      of T4 to T3 and, consequently, less T4 is converted into T3.

PMID- 7625290
TI  - Effect of hydrothermal treatment of rice straw on its composition and in sacco
      digestibility and in vitro fermentation by rumen microorganisms.
AB  - Chemical composition, in sacco rumen disappearance of various cell wall
      constituents (CWC) and in vitro fermentation pattern of hydrothermally treated (1
      to 14 kp/cm2 pressure for 5 min) rice straw was examined. At 10 kp/cm2 pressure
      treatment (maximum effect) the contents of dry matter (DM), organic matter (OM),
      neutral detergent fibre (NDF), acid detergent fibre (ADF), hemicellulose (HC) and
      cellulose (CE) were decreased by 32.5, 35.3, 27.8, 10.2, 61.2 and 25.1%,
      respectively (P < 0.05), over the untreated control. The in sacco rumen
      disappearance of DM, OM, HC and CE from rice straw treated at 8 kp/cm2 pressure
      (maximum effect) and incubated for 48 h was increased from 53.2 to 77.7, 52.4 to
      80.3, 49.5 to 82.0 and 49.2 to 79.3%, respectively (P < 0.01). In vitro
      production of total volatile fatty acids and the content of TCA-insoluble protein
      was also significantly higher (P < 0.05) on treated compared with untreated
      straw.

PMID- 7625291
TI  - Complex study of the physiological role of cadmium. I. Cadmium and its
      physiological role.

PMID- 7625292
TI  - Complex study of the physiological role of cadmium. II. Effect of cadmium load on
      the cadmium content of eggs.
AB  - The possibility of "cadmium (Cd) contamination" of eggs and the dynamics of Cd
      accumulation were studied. A total of 40 (4 x 10) Japanese quails weighing 155
      200 g, being at the middle phase of egg production and kept on batteries in a
      climatized animal house were used. The birds were fed a standard quail layer diet
      and drank tap-water ad libitum. With the exception of the control group (Cd-0),
      the diet of the other three groups was supplemented with Cd sulphate
      homogeneously mixed in the diet so that it contained 75 mg (Cd-75), 150 mg (Cd
      150) and 300 mg (Cd-300) per kg. During the 37-day feeding trial the quails'
      behaviour, health status and daily egg production were monitored and the birds
      were weighed weekly. The egg production of the experimental groups, particularly
      of those exposed to a high Cd load, rapidly decreased: at the highest Cd load
      (300 ppm) egg production completely ceased at days 10-11 of the trial. The total
      Cd content of the eggs rose already from the 3rd day of the feeding trial and by
      day 10 it reached a value of 0.777 mg/kg dry matter in the eggs of quails of
      group Cd-75. This was about five times the value measured in the control quails'
      eggs (0.165 mg/kg dry matter). The Cd content of the egg-white and egg-yolk
      (maximum values: 0.212 and 0.107 mg/kg dry matter) also increased to about 2 or 3
      times that measured in the control eggs. The Cd content of eggs reached the peak
      in the 2nd week of the feeding trial, then started to decrease, and in the 3rd
      and 4th weeks not even the eggs laid by quails exposed to a high Cd load
      contained more Cd than about twice the concentration measured in the controls'
      eggs. The elucidation of this hitherto not studied process requires further
      investigations. The phenomenon may be due to a lack of the protein necessary for
      Cd transport and to the impairment of Cd absorption and of the excretory activity
      of the oviduct. The higher Cd concentrations measured in the egg were accompanied
      by markedly elevated Fe, K and S values. In the egg samples collected in the 4th
      week a substantial reduction in Ca and P concentration was observed. As regards
      the mineral elements measured in the egg-shell, a significant negative
      correlation was established between the concentration of Cd and those of Zn, Mg
      and Ca.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7625293
TI  - In vitro and in vivo motility studies of 99mTc HM-PAO labelled sperm cells.
AB  - The motility of 99mTc HM-PAO radiolabelled sperm cells, labelled as described
      previously (Balogh et al., 1992) was studied. The active migration of spermatozoa
      was demonstrated in capillary tubes containing bovine oestrous mucus, using an in
      vitro motility analyzer. Like nonlabelled sperm cells, the labelled spermatozoa
      covered a 4-5 cm distance in the capillary tubes during a 10-min run. In vitro
      motility testing of labelled spermatozoa from different animal species (cattle,
      rabbit, sheep, horse) did not reveal significant differences. The distribution of
      spermatozoa within the female genital tract was studied in a previously described
      animal model (rabbit) and in two new models (sheep, chicken). This method enables
      the determination and visualization of sperm distribution by a noninvasive
      technique. The results of in vivo motility tests pave the way for the
      introduction of a method of unprecedented specificity, which serves for studying
      the penetrability of the oviduct to spermatozoa.

PMID- 7625294
TI  - Effects of sample handling temperatures on bovine skim milk progesterone
      concentrations.
AB  - The effect of incubation of whole milk at various temperatures and times on the
      amount of progesterone (nmol/l) in the skim milk fraction was determined. For
      this study, milk samples were obtained from 10 pregnant Holstein cows. The whole
      milk samples were incubated at 37 degrees C (near normal body temperature of the
      cow) for 4 h and the initial skim milk progesterone concentration was determined.
      After that, the experiment was carried out in two main steps: (I) The test tubes
      containing the whole milk were divided into 4 groups and incubated at different
      temperatures (0, 4, 20 and 37 degrees C). Samples were removed at 30, 60, 90 and
      120 min. (II) After 120 min of incubation at different temperatures, the
      remaining test tubes were returned to the water bath at 37 degrees C for another
      30, 60 and 90 min. The initial average of skim milk progesterone concentrations
      after incubating the whole milk at 37 degrees C for 4 h was 11.0 +/- 4.4 nmol/l.
      When the whole milk was incubated at 0 degrees C, the skim milk progesterone
      concentration increased (P < 0.05) to 14.6 nmol/l at 30 min and reached 16.2
      nmol/l at 60 min of incubation. At 4 degrees C incubation temperature, skim milk
      progesterone increased significantly (P < 0.05) to 15.3 nmol/l and reached 16.9
      nmol/l after 90 min. When the whole milk was left at 20 degrees C, the initial
      skim milk progesterone values decreased to 9.5 nmol/l after 30 min incubation and
      no further decreases were found even if the whole milk was returned to 37 degrees
      C for 90 min.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7625295
TI  - Effect of luteinizing hormone and estradiol on in vitro maturation of follicular
      oocytes in goat (Capra hircus).
AB  - In vitro maturation of goat follicular oocytes in TALP medium supplemented with
      variable concentrations of luteinizing hormone (LH) [5-20 micrograms/ml] and
      estradiol [1 microgram/ml] was studied. Incubation of viable oocytes was carried
      out at 38.5 degrees C under liquid paraffin in 5% carbon dioxide/air mixture for
      24 h. At 0 h all the oocytes were in germinal vesicle (GV) stage, each with a
      good cumulus. The cumulus expansion increased linearly with increasing
      concentrations of LH and a fixed concentration of estradiol [1 microgram/ml] at
      24 h of incubation. Germinal vesicle breakdown (GVBD) was observed in 28% of the
      oocytes at 5 micrograms/ml concentration of LH and the same increased to 87% at
      10 micrograms/ml of LH with 13% oocytes at metaphase II. At 20 micrograms/ml of
      LH, 45% of the oocytes were at metaphase II and the rest were at metaphase I. LH
      and estradiol seem to be important for acquisition of maturation competence in
      goat follicular oocytes.

PMID- 7625296
TI  - The production of K88 antigen by Escherichia coli and Salmonella typhimurium
      strains with recombinant DNA.
AB  - Expression of K88ab antigen by strains with recombinant DNA, differing in
      molecular weight or promoter, was subjected to investigation. Strains with
      recombinant DNA produced greater amounts of antigen than did field isolates.
      Maximal production was recorded for the E. coli C600 strain with 10.85 kb
      recombinant DNA with promoter P1 of the pBR322 vector. The substitution of
      promoter Ptac for promoter P1 did not result in an increased expression of K88ab
      antigen. The production of K88ab antigen by Salmonella typhimurium TM333 with
      recombinant DNA was on a level comparable to that of E. coli C600 or E. coli
      HB101 strains with the same recombinant DNA.

PMID- 7625297
TI  - Pattern of trauma resulting from motorcycle accidents in Nigerians: a two-year
      prospective study.
AB  - A two-year prospective study of injuries sustained from motor-cycle accidents
      (MCA) was conducted at the University of Ilorin Teaching Hospital, Ilorin,
      Nigeria, in 1983 and 1984 after repeal of the national mandatory helmet law. MCA
      patients constituted 10.3% of 715 road traffic accident (RTA) patients and also
      presented a 5.7:1 male preponderance. Peak age was 18 to 30 years. Nearly 75%
      sustained lower extremity, chest and cranioencephalic injuries. Non-operative
      management sufficed in 34 patients (45.9%) while 30 (40.5%) and 10 (13.5%)
      require operations respectively. Eighteen (24.3%) and 17 (23.0%) patients
      required local/spinal and general anesthesia respectively. Mortality was 6.8% (5
      patients). This analysis of MCA injuries provides objective basis for current
      comparison with what obtains in jurisdictions with/without mandatory helmet law
      and future comparison when the law is re-enacted in our state.

PMID- 7625298
TI  - Peritoneal dialysis in a private hospital: a case for chronic peritoneal dialysis
      programme.
AB  - Twenty patients presenting with renal failure were treated with peritoneal
      dialysis in a private hospital in Nigeria. Of the nine patients with acute renal
      failure, six survived. Four patients with chronic failure was maintained on
      Intermittent Peritoneal Dialysis and were sustained for variable periods. There
      were some complications, especially peritonitis and catheter obstruction. It is
      suggested that a chronic peritoneal dialysis programme should be encouraged in a
      developing country like Nigeria. This is an alternative to haemodialysis. Our
      suggestions are based on its proven efficacy, comparatively lower cost, easy
      maintenance and convenience to patients.

PMID- 7625299
TI  - AIDS knowledge, attitude and behaviour patterns among university students in
      Ibadan, Nigeria.
AB  - This study investigated the knowledge, attitudes and personal behaviours of
      University students on AIDS. Two hundred and fifty students from the University
      of Ibadan randomly selected from eight faculties were surveyed. Results indicated
      that 58.7% of the subjects knew that AIDS is caused by a virus but 72.6% thought
      the disease could be spread through kissing, hugging or shaking hands and 48.0%
      believe they cannot have AIDS. Most students showed a high degree of aversion to
      AIDS victims while about a quarter reported having multiple sexual partners in
      the last five years. The results suggest that well organised, specifically
      targeted educational programmes are needed for University students.

PMID- 7625300
TI  - Acute lower respiratory infections in hospitalised urban pre-school Nigerian
      children: a clinical overview.
AB  - One hundred and three hospitalised urban pre-school Nigerian children aged 2
      weeks to 4 years with various acute lower respiratory tract infection (ALRI),
      were studied prospectively over a 9- month period (August 1985 - April 1986).
      Overlapping seasonal peaks, corresponding to the rainy/early harmattan months of
      August through November were most noticeable for the two major viral ALRI
      syndromes namely, bronchiolitis and croup. The overall M:F ratio was 1.1:1, but a
      corresponding ratio of 1.6:1 was recorded in the infants. The commonest ALRI
      symptoms were cough, breathlessness and fever while chest wall retraction, nasal
      flaring, tachypnoea and auscultatory crepitations were the most frequently
      recognised physical findings. Grunting respiration was recognised in 26 patients,
      majority of whom had pleural effusion and/or severe bronchopneumonia.
      Bronchopneumonia was the single commonest ALRI diagnosis, recorded alone or in
      combination with another lower respiratory syndrome, in 64 (61.2%) of the 103
      cases. The croup:bronchiolitis: pneumonia ratio was 1:2.3:8.3. Nasopharyngitis
      was recorded in 42 (40.7%) of cases, and was frequently associated with the
      presumably viral ALRI syndromes of croup and bronchiolitis. Pleural effusion,
      frequently purulent, was the commonest respiratory complication, while heart
      failure and anaemia were the most frequently recognised associated conditions,
      found predominantly in patients with pneumonia and bronchiolitis. There was an
      overall ALRI case-fatality of 7.8%, representing 8 deaths, in 3 of whom measles
      was a co-morbid condition. All the 8 deaths had a final diagnosis of pneumonia
      with or without other ALRI syndromes/associated complications. While subjects
      with complicating pleural effusion recorded the longest mean duration of
      hospitalisation, those with bronchiolitis had the shortest duration of
      hospitalisation and no death. The epidemiologic, as well as the diagnostic and
      therapeutic implications of our observations are discussed.

PMID- 7625301
TI  - Effects of two antihistamines on chloroquine and histamine induced weal and flare
      in healthy African volunteers.
AB  - This study investigated the effects of single doses of clemastine (2mg orally),
      mepyramine (2 micrograms intradermally) and placebo on weal and flare caused by
      intradermal chloroquine 2.5mg and histamine 2 micrograms in 11 healthy black
      subjects who experienced generalised pruritus with oral chloroquine. Compared
      with placebo, both antihistamines caused significant reductions in histamine
      induced weal and flare. By contrast, chloroquine-induced weal and flare were not
      significantly altered by clemastine or mepyramine when compared with placebo. It
      is concluded that histamine is unlikely to be the main mediator of chloroquine
      induced weal and flare. These findings are in consonance with the lack of
      significant effect of antihistamines on chloroquine-induced generalised pruritus.

PMID- 7625302
TI  - The effect of antibacterial agents on plasma vitamin C levels.
AB  - Previous report on the estimation of plasma ascorbic acid levels in patients with
      chronic osteomyelitis indicated that the plasma ascorbic acid level is reduced in
      patients on antibiotics. The plasma study of the effects of anti-bacterial agents
      on plasma ascorbic acid in vitro, was carried out to substantiate the hypothesis
      than these agents lower plasma ascorbic acid levels. Increasing amounts of each
      of seven anti-bacterial agents: ampicillin, chloramphenicol, cefotaxime,
      gentamycin, benzyl and procaine penicillin combination (seclopen), co
      trimoxazole, and streptomycin significantly (P < 0.01, r = -0.9587) reduced
      plasma vitamin C levels in vitro. There was moderate but insignificant reduction
      in plasma vitamin C levels with clindamycin (r = -0.799). The reduction of the
      plasma vitamin C levels observed in the presence of the eighth anti-bacterial
      agent, clindamycin, lacked significance (r = -0.799). The cause of this reduction
      of plasma vitamin C levels by anti-bacterial agents in vitro is not yet
      understood. A supplement of vitamin C may be required in patients on anti
      bacterial agents.

PMID- 7625303
TI  - A primary health care baseline survey in a rural district in Zambia.
AB  - In many developing countries health data are insufficient. These data are needed
      to get valid information to make decisions about health programmes. Baseline
      surveys are in terms of economy and resources a method which is fruitful. These
      baseline surveys should not only be performed at country and province level.
      Baseline surveys at district level is needed to monitor local needs. The present
      baseline survey was focus on immunization, diarrhoea incidence and diarrhoea
      treatment, sanitation and children nutrition status. 388 households were visited
      in a random 30 cluster baseline survey in Choma district of Zambia. It revealed
      that 79% of the children aged 12-23 months was fully immunized and the drop-out
      rate in polio and DPT vaccination routines was as low as 9 and 12% respectively.
      The incidence of diarrhoea disease was high and estimated at 4.8 episodes per
      child per year. ORS and SSS were used as treatment in 52% and 15% of all cases.
      More than 90% of mothers would seek help at RHCs or PHCs in case of diarrhoea.
      About 2/3 of the households had no safe water supply and 2/3 no pitlatrine. Only
      a few had a refuse pit. The nutrition status of children were assessed by using
      upper arm circumference measurements. Only about 40% of the children age 12-23
      month and about 75% of children aged 24-59 months respectively were adequately
      nourished. The district had in this survey a fair immunization programme but
      intensified sanitary and nutritional programmes seem justified. Periodic baseline
      surveys with 2-3 years interval is recommended to determine the impact and future
      direction of the programme.

PMID- 7625304
TI  - Glomerular function in sickle cell disease patients during crisis.
AB  - An 8 month prospective study was carried out in 20 adult sickle cell disease
      (SCD) patients 16 sickle cell anaemia (Hbss) and 4 sickle cell Hbc disease
      (Hbsc); who had vaso-occlusive crises within the study period to determine the
      extent of the effect of sickle cell crisis on glomerular function in SCD patients
      during crisis. The male: female ratio was 1:57 and their mean age was 21.1 +/-
      7.9 years. Creatinine clearance (CCr), as an index of glomerular function, was
      determined at the pre-crisis, crisis, 2 and 4 weeks post-crisis and at the end of
      the study period. The mean values of their CCr dropped from 113.37 +/-
      33.80mls/min at pre-crisis stage to 96.39 +/- 30.13mls/min during crisis (p <
      0.001) indicating glomerular dysfunction. It improved significantly to 107.75 +/-
      30.20mls/min at 4 weeks post-crisis (p < 0.001). There was no significant
      differences in the mean values of CCr at the end of the study (116.20 +/-
      31.43mls/min) compared to the pre-crisis stage (p > 0.05). It is concluded that
      glomerular dysfunction in SCD patients during crisis is potentially reversible.

PMID- 7625305
TI  - Characterisation of ingenol: an inflammatory diterpene from some Nigerian
      Euphorbia and Elaeophorbia species.
AB  - Inflammatory latices of Euphorbia deightonii, Euphorbia desmondi, Elaeophorbia
      drupifera and Elaeophorbia grandiflora were found to contain ingenol as the
      parent alcohol of the diterpene esters. The chemotaxonomic significance of the
      occurrence of ingenol in the genus Elaeophorbia is discussed.

PMID- 7625306
TI  - Pregnancy outcome after illegal induced abortion in Nigeria: a retrospective
      controlled historical study.
AB  - The effect of illegal abortion on subsequent reproduction was studied in 46
      Nigerian women who gave a history of illegal termination of pregnancy. There was
      a statistically significant increase in the incidences of premature rupture of
      membranes, premature labour and low birth weight when compared to 53 primigravida
      who gave no such history of abortion. The perinatal mortality was also
      significantly higher in the abortion group. In contrast, pre-eclampsia was less
      common in the abortion group. These findings indicate that illegal abortion has
      adverse effects on pregnancy outcome in Nigerian women.

PMID- 7625307
TI  - Immunoglobulin and immune complex levels in Nigerians with acute lymphoblastic
      leukaemia.
AB  - Twenty-five patients with acute lymphoblastic leukaemia (ALL) aged 10 months to
      43 years and twenty-five age and sex matched healthy control subjects were
      investigated in this study. Serum immunoglobulins A, G and M levels were measured
      by single radial immunodiffusion method and immune complex levels estimated by
      polyethylene glycol precipitation technique. Significant increase in immune
      complexes and decrease in immunoglobulin G were observed in the patients.
      Although not statistically significant, the patients had a lower mean level of
      immunoglobulin A, and a higher mean immunoglobulin M concentration than the
      controls. Hypoimmunoglubulinaemia observed in this study may contribute to the
      aetiology of ALL or be an effect of the disease. Raised immune complexes could
      result from specific antibodies combining with tumour associated or microbial
      antigens. Immunoglobulin G levels showed a significant positive correlation with
      survival in the patients. The adverse effect of reduced immunoglobulin G on the
      prognosis of ALL is probably due to compromised immunity in the patients.

PMID- 7625308
TI  - Nasopharyngeal carcinoma in the differential diagnosis of intracranial
      subtemporal masses.
AB  - Six cases of nasopharyngeal carcinoma presenting primarily to the neurosurgical
      service of the University of Nigeria Teaching Hospital as intracranial
      subtemporal masses are discussed. This mode of initial presentation is very rare.
      The clinical features are described and the need to examine and biopsy the
      nasopharynx in cases of intracranial space occupying lesions in the subtemporal
      or posterior fossa regions is emphasised.

PMID- 7625309
TI  - Formulation of water disinfectant tablets for rural communities in Nigeria.
AB  - A water disinfectant tablet containing calcium hypochlorite as the main
      ingredient has been developed using a variety of excipients to improve the tablet
      characteristics. Avicel, polyvinylpyrrolidone, sodium hydrogen carbonate, calcium
      carbonate, sodium chloride and potassium chloride were used. Inclusion of
      polyvinylpyrrolidone together with calcium carbonate gave better tablet
      characteristics. Avicel though gave better tablet characteristics, promoted loss
      of chlorine from the tablets. Inclusion of inorganic salts were not satisfactory
      as they, enhanced atmospheric water absorption.

PMID- 7625310
TI  - Some practical aspects of teaching medicine in Africa.

PMID- 7625311
TI  - The need for an orientation course on the use of clinical laboratories.
AB  - A recent study in our institution has confirmed a relationship between lack of
      adequate undergraduate exposure to the clinical laboratories and subsequent
      negative attitudes and improper use of these laboratories by medical graduates.
      An orientation course on the use of the clinical laboratories is here proposed,
      for new medical graduates, at the commencement of internship training, to help
      remedy this defect and improve usage of the laboratories.

PMID- 7625312
TI  - Intestinal bilious vomiting--an unusual presentation of intestinal atresia in the
      newborn.
AB  - A female pre-term infant was delivered to a teenage mother who had fresh
      "meconium-stained" liquor during labour. At resuscitation, the baby had copious
      amount of greenish effluent coming from and also sucked out of the pharynx and
      stomach. She was subsequently diagnosed as having ileal atresia; the initially
      thought "meconium stained" liquor was the result of in-utero bilious vomiting,
      secondary to the intestinal obstruction. She had resection of the atretic bowel
      and end to back anastomosis; she died 24 days post-operatively.

PMID- 7625313
TI  - Canadian vs. U.S. health care: which system is 'best'?

PMID- 7625314
TI  - Semen and the vaginal fish odor.

PMID- 7625315
TI  - East African trypanosomiasis in the United States.

PMID- 7625317
TI  - The Oregon Death with Dignity Act.

PMID- 7625316
TI  - New physician organization for promotion of breast feeding.

PMID- 7625318
TI  - Family physicians reaching out to medical students.

PMID- 7625319
TI  - AHCPR post-stroke rehabilitation guideline. Agency for Health Care Policy and
      Research.

PMID- 7625320
TI  - Acute pancreatitis: diagnosis and management.
AB  - Acute pancreatitis is a clinical syndrome characterized by midepigastric pain,
      nausea and vomiting. Numerous etiologies have been linked with this entity,
      principally alcoholism and biliary disease. Once the clinical suspicion of
      pancreatitis is confirmed, supportive therapy with intravenous hydration and
      close observation is effective in the vast majority of patients. Lack of
      improvement may indicate the need to search for a local complication such as
      pseudocyst or abscess. Fine-needle aspiration of suspected infected collections
      should be performed under computed tomographic guidance. Surgical intervention
      may be required if infection is confirmed. Evidence of the systemic complications
      of pancreatitis mandates intensive care monitoring.

PMID- 7625321
TI  - Barriers to diagnosing anxiety disorders in family practice.
AB  - Although anxiety disorders are common, their accurate diagnosis and effective
      treatment may be hindered by both physician and patient factors. Both denial on
      the part of patients and avoidance of conflict by physicians may be based on
      outdated concepts of stigma attached to "mental" illness and failure to accept
      the biopsychosocial model of illness. Physician failure to discriminate between
      the different anxiety conditions and to recommend the treatment appropriate for
      each specific diagnosis are additional significant barriers. The situation is
      further complicated when the patient's symptoms change over time. Although both
      physician and patient may experience significant discomfort in exploring anxiety
      symptoms, a thorough clinical history is essential to the diagnosis and provides
      the basis for successful management of these conditions.

PMID- 7625322
TI  - Post-stroke rehabilitation: assessment, referral and patient management. Post
      Stroke Rehabilitation Guideline Panel. Agency for Health Care Policy and
      Research.

PMID- 7625323
TI  - Management of cat and dog bites.
AB  - An estimated 1 to 2 million Americans are bitten by cats and dogs each year. Most
      victims are children who are bitten by dogs. Dog and cat bite wounds may appear
      trivial, but if they are not managed appropriately, they can become infected and
      may result in functional impairment. Cat bite wounds on the hand have the
      greatest risk of infection. Pasteurella multocida, isolated in over half of all
      cat bite wounds and in 20 to 30 percent of dog bite wounds, can cause serious
      infection with severe complications. Amoxicillin-clavulanate is recommended for
      the outpatient treatment of dog and cat bite wounds. Tetanus immunization status
      and the risk of rabies infection should be routinely addressed in bite wound
      management.

PMID- 7625324
TI  - Acute exertional rhabdomyolysis.
AB  - Acute exertional rhabdomyolysis is caused by a skeletal muscle injury that
      results in the release of myoglobin and other cellular contents into the
      circulatory system. Recent reports suggest that acute exertional rhabdomyolysis
      is more common and more serious than previously realized. Mild to moderate acute
      exertional rhabdomyolysis can result in hyperkalemia, hypernatremia, lactic
      acidosis and hyperphosphatemia. Disseminated intravascular coagulation, renal
      failure and compartmental syndrome may also occur. The physician should maintain
      a high index of suspicion for acute exertional rhabdomyolysis in patients who
      present with symptoms of an overexertion injury, most commonly pain and swelling
      in the affected muscles. Special attention should be given to evaluating the
      history for occupational, recreational, environmental and medical risk factors
      for rhabdomyolysis. Screening may be performed with a simple urine dipstick test;
      if the urine is orthotoluidine-positive, the diagnosis should be confirmed with
      measurement of the serum creatine kinase level. Early intervention with
      aggressive hydration and close monitoring for metabolic, renal or hematologic
      complications may prevent serious injury or death.

PMID- 7625325
TI  - Neonatal circumcision techniques.
AB  - Neonatal circumcision is most commonly performed using one of three techniques-
      the Mogen clamp, the Gomco clamp or the Plastibell device. With all three
      techniques, careful selection and preparation of patients is essential. Informed
      consent must be obtained from parents or guardians, based on an objective
      understanding of the medical and social implications of circumcision, including
      potential complications from the procedure. Measures for creating an aseptic
      field, anesthesia and positioning of the infant do not vary with the technique
      selected. Both the Mogen and Gomco clamps protect the glans while producing crush
      injury to the prepuce, which is then surgically removed. The Plastibell device
      induces necrotic tissue, which is sloughed off, along with the plastic shield,
      within a week or so. Although complications from neonatal circumcision are rare,
      hemorrhage, local infection, sepsis, meatal ulceration and poor cosmetic results
      have been reported.

PMID- 7625327
TI  - Postpartum fever.
AB  - Postpartum fever is a common obstetric complication. It often results from
      endometritis but can also be caused by urinary tract infection, would infection
      or phlebitis. The rate of endometritis is higher among patients who have a
      cesarean delivery, compared with those who have a vaginal delivery. Postpartum
      febrile episodes in which temperatures are less than 38.4 degrees C (101.1
      degrees F) often resolve without intervention, especially when they occur in the
      first 24 hours after delivery. Treatment options for patients whose febrile
      episodes do not resolve spontaneously or are higher than 38.7 degrees C (101.6
      degrees F) during the first 24 hours or higher than 38.0 degrees C (100.4 degrees
      F) on any two of the first 10 days postpartum include administration of
      antibiotics with specific activity against anaerobic bacteria. Additional
      diagnostic modalities, such as computed tomography, ultrasonography, heparin
      administration and surgical exploration, should be employed when the patient
      fails to respond to antibiotic therapy.

PMID- 7625326
TI  - Fact sheet for physicians regarding neonatal circumcision. American Academy of
      Family Physicians.
AB  - Neonatal circumcision is a quick and generally safe procedure when performed by
      an experienced physician. Complications are few and usually minor. It has many
      potential benefits. It is also more economical and avoids the risk of general
      anesthesia to perform the procedure early in life, rather than later. The
      American Academy of Family Physicians recommends that an objective discussion,
      answering the questions of the parents, should precede any truly informed
      consent. The physician should document the discussion and resultant decision in
      the medical record.

PMID- 7625328
TI  - Exercise prescription.
AB  - Exercise can increase longevity and improve overall health and quality of life.
      Since a large proportion of Americans have a sedentary lifestyle, exercise
      counseling should be a part of routine health maintenance. Physicians need to
      provide patients with information about the specific benefits of exercise and
      motivate them to increase their physical activity. Physicians should encourage
      all adults, including those who elect not to participate in a formal exercise
      program, to accumulate 30 minutes or more of moderate-intensity physical activity
      on most days of the week. Before beginning an exercise program, selected higher
      risk patients may need to be evaluated with a physical examination and a
      treadmill test. Many patients benefit from a preexercise determination of fitness
      and specific instructions for monitoring their heart rate to maintain exercise
      within appropriate target ranges. A formal exercise prescription should include
      specific advice about the type, frequency, intensity, duration and progression of
      physical activity. Once an exercise regimen has begun, injury prevention and
      adherence to the program become important.

PMID- 7625329
TI  - Current surgical treatment of valvular heart disease.
AB  - Surgery for valvular heart disease has undergone important refinements during the
      past several years. The general indications for valvular surgery are the presence
      of symptoms that interfere with the patient's lifestyle and that cannot be
      controlled with medical therapy, and indications of a threat to continued
      survival, such as angina, dyspnea, effort syncope or progressive impairment of
      ventricular contractility. Infective endocarditis may also be an indication for
      valvular surgery in patients with congestive heart failure, recurrent embolism,
      persistent infection despite antibiotic therapy, large vegetations or progressive
      conduction defects. Surgical procedures for the treatment of valvular heart
      disease include reconstruction techniques and valve replacement procedures.
      Reconstructive surgery minimizes the amount of materials that must be implanted.
      Advances in myocardial preservation have reduced the risk of such complex cardiac
      surgical procedures as multiple valve replacements and valve replacements
      combined with coronary artery bypass surgery. Follow-up care is important to
      monitor valve function, fluid balance and anticoagulation.

PMID- 7625330
TI  - Photosensitivity reactions: a case report involving NSAIDs.
AB  - Photosensitivity reactions associated with the use of prescription or over-the
      counter drugs may be classified as phototoxic (caused by potentiation of solar
      energy by a drug) or photoallergic (in which the combination of a
      photosensitizing agent and light evokes a true cell-mediated hypersensitivity
      response). A case of a photoallergic response related to the use of piroxicam is
      included to illustrate the presentation and management of photosensitivity
      reactions to nonsteroidal anti-inflammatory drugs.

PMID- 7625331
TI  - Acid-base disorders: classification and management strategies.
AB  - Acid-base disorders are common in clinical practice. Simple acid-base
      disturbances include metabolic acidosis, metabolic alkalosis, respiratory
      acidosis and respiratory alkalosis. Each can be clearly identified using a common
      clinical approach. Proper understanding of acid-base disorders requires knowledge
      of normal physiology. Each of the simple acid-base disorders can be diagnosed by
      obtaining a good history and performing a physical examination, followed by
      determinations of electrolyte levels, anion gap and pH. The degree and nature of
      compensation should then be analyzed. Finally, the ratio of the change in anion
      gap to the change in serum bicarbonate (delta AG/delta HCO3-) should be
      determined. When this diagnostic process is applied, proper identification of the
      disorder can be made and management can be undertaken. Mixed acid-base disorders
      can also be identified and managed using this method.

PMID- 7625334
TI  - Update on AIDS in men who have sex with men.

PMID- 7625333
TI  - ACIP updates recommendations for the use of antiviral agents in influenza.
      Advisory Committee on Immunization Practices.

PMID- 7625332
TI  - Antihistamines: the old and the new.
AB  - Several pharmacologic agents provide antihistamine effects by acting at the H1
      histamine receptor site. The classic agents are relatively nonselective,
      resulting in a wide range of effects, both therapeutic and undesirable. The newer
      agents preferentially block peripheral H1 receptor sites and, consequently, have
      fewer side effects, including sedation. Antihistamines are useful in the
      treatment of allergic conditions, Parkinson's disease, insomnia and some forms of
      nausea, and provide symptomatic relief of cough and other conditions associated
      with respiratory tract infections. Certain agents may play a role in the
      treatment of asthma and anorexia. Selection of a specific agent should be based
      on cost and the minimization of side effects. The classic antihistamines provide
      an inexpensive and highly effective means of treating histamine-mediated
      symptoms. The bothersome central nervous system side effects can be alleviated by
      taking the drugs at bedtime; their prolonged tissue half-life allows dosing once
      or twice a day for 24-hour clinical relief. The newer, more expensive nonsedating
      antihistamines are acceptable alternatives for patients who are incapable of
      tolerating the effects of classic agents.

PMID- 7625335
TI  - Evaluation of magnetic resonance imaging for quantification of intraabdominal fat
      in human beings by spin-echo and inversion-recovery protocols.
AB  - We evaluated two magnetic resonance imaging (MRI) methods, spin echo and
      inversion recovery (IR), for quantification of intraabdominal fat in a subgroup
      of participants from the Atherosclerosis Risk in Communities (ARIC) Study. Both
      methods were used previously to quantify visceral fat, and the IR but not the
      spin echo method has been validated by comparison with computed tomography in
      human beings. In the present study, the reliability of both methods was
      excellent: reliability coefficients comparing two readers on the same scan were
      0.9574 for IR (n = 158) and 0.9254 for spin echo (n = 47) when random effects
      models with log-transformed data were used. A comparison of visceral fat areas in
      47 subjects with both IR and spin echo indicated that IR gave a slightly higher
      mean area than did spin echo: 134.9 compared with 129.8 cm2. However, a mixed
      model analysis of variance (ANOVA) of the log-transformed data showed no
      statistical difference between either method or readers in the comparison of IR
      and spin echo. These data suggest that the IR and spin echo protocols evaluated
      in this communication are comparable with one another and reliable for estimation
      of intraabdominal fat.

PMID- 7625336
TI  - Increased fat oxidation during Ramadan fasting in healthy women: an adaptative
      mechanism for body-weight maintenance.
AB  - Possible effects of Ramadan fasting on anthropometric and metabolic variables
      were investigated in healthy Tunisian Moslem women. Total daily energy intake
      remained unchanged whereas the qualitative components of nutrients were markedly
      affected. Neither body weight nor body composition were influenced by Ramadan
      fasting. Results also indicate the concomitant decrease of plasma insulin
      concentrations with respiratory and energy expenditure during Ramadan. The
      circadian evolution of nutrient oxidation rates was modified. Fat oxidation was
      increased and carbohydrate oxidation was decreased during the light span of the
      nycthemeron. Qualitative and quantitative circadian changes in feeding associated
      with Ramadan might be counterbalanced by specific metabolic changes in order to
      preserve normal body weight and composition.

PMID- 7625337
TI  - Twenty-four-hour energy expenditure and its components in prepubertal children as
      determined by whole-body indirect calorimetry and compared with young adults.
AB  - The aim of the present study was to compare total daily and circadian variations
      of energy expenditure (EE) in 21 prepubescent 10-y-old children (12 boys and 9
      girls) and 18 23-y-old adults (9 men and 9 women) under the same conditions by
      using two large calorimetric chambers. The volunteers followed similar activity
      programs with four periods of exercise on a cyclergometer. Total daily and
      sleeping EE adjusted for differences in fat-free mass (FFM) and age were
      significantly higher in children than in adults by 35% and 27%, respectively (P <
      0.001). EE during sleep decreased by 2% per hour in both age groups. Heart rate
      was significantly higher in girls than in boys. The energy cost of cycling,
      adjusted for differences in FFM and external mechanical power, was not
      significantly different in children and adults. The differences in EE between
      children and adults may partly result from a higher proportion of internal organs
      in the FFM.

PMID- 7625338
TI  - Covert manipulation of dietary fat and energy density: effect on substrate flux
      and food intake in men eating ad libitum.
AB  - This study assessed whether human food intake is regulated by negative feedback,
      directly or indirectly, from carbohydrate stores (glycogenostatic model). Six men
      were studied on three occasions during 7 d of whole-body indirect calorimetry,
      throughout which they had ad libitum access to one of three covertly manipulated
      diets: low fat (20% of energy as fat, 67% of energy as carbohydrate, and 13% of
      energy as protein; 4.80 kJ/g; LF), medium fat (40% of energy as fat, 47% of
      energy as carbohydrate, and 13% of energy as protein; 5.59 kJ/g; MF), or high fat
      (60% of energy as fat, 27% of energy as carbohydrate, and 13% of energy as
      protein; 7.04 kJ/g; HF). Energy intakes increased with percent fat (F[92,60] =
      36.7; P < 0.001), producing average daily balances of -0.27, 0.77, and 2.58 MJ/d
      during the LF, MF, and HF diets, respectively. Changes in carbohydrate stores
      were attenuated by autoregulatory changes in carbohydrate oxidation. Carbohydrate
      balance showed a negative relation to the subsequent day's energy balance (t =
      2.696; P = 0.0082) but explained only 5.5% of the variance. The relation for fat
      was positive (t = 5.245; P < 0.0001), accounting for 19.9% of the variance
      (stepwise regression). LF, lower-energy diets are more satiating than are HF
      higher-energy diets, but carbohydrate stores per se did not entirely account for
      the change that diet composition had on energy intake. This study suggests that
      protein and carbohydrate have potential to reduce subsequent energy intake
      whereas there was no apparent reductive effect due to fat.

PMID- 7625339
TI  - Covert manipulation of the ratio of dietary fat to carbohydrate and energy
      density: effect on food intake and energy balance in free-living men eating ad
      libitum.
AB  - We previously increased the energy density and fat content across three diets
      (factorial design), which led to a marked increase in energy intake in six men
      over 7 d while continuously resident in a whole-body indirect calorimeter. In the
      present study we fed the same diets to seven men who were resident in, but not
      confined to, a metabolic suite for 2 wk/diet. This added a component of increased
      physical activity. The fat, carbohydrate, and protein contents, respectively, of
      each diet (as a percent of energy) were as follows: low-fat (LF), 20:67:13;
      medium-fat (MF), 40:47:13; and high-fat (HF), 60:27:13. Energy density increased
      as the percent of fat in the diet increased. Energy intakes from the LF, MF, and
      HF diets (9.11, 10.32, and 12.78 MJ/d, respectively) were almost identical to
      those in our calorimeter study (9.02, 10.2, and 12.35 MJ/d, respectively) whereas
      energy expenditures (estimated by the doubly labeled water method) were 12.45,
      12.10, and 11.97 MJ/d on the LF, MF and HF diets, respectively, compared with
      9.48, 9.53, and 9.78 MJ/d, respectively, in our calorimeter study. This finding
      suggests that diet composition and energy expenditure combined influence energy
      balance in humans.

PMID- 7625340
TI  - Dietary energy requirements of young and older women determined by using the
      doubly labeled water method.
AB  - There is little information on the effects of age on energy requirements in
      women. This issue was investigated in a cross-sectional study of 10 normal-weight
      young women aged 25.2 +/- 1.1 y (mean +/- SEM) and 10 normal-weight older women
      aged 74.0 +/- 1.4 y. In a 9-d study, measurements were made of free-living total
      energy expenditure (TEE) by using the doubly labeled water technique, body
      composition by using hydrodensitometry, and resting energy expenditure (REE) by
      using indirect calorimetry. Mean values for reported levels of strenuous activity
      were within the expected range in both groups (31 +/- 13 min/d in the young group
      and 7 +/- 2 min/d in the older group). Energy requirements expressed as the ratio
      of TEE to REE were 1.80 +/- 0.10 and 1.62 +/- 0.06 (P < 0.01) in the young and
      older group, respectively. When values for REE predicted from body weight (pREE)
      were used, as suggested in the current recommended dietary allowances (RDAs), the
      ratios of TEE to pREE in the two groups were 1.85 +/- 0.10 and 1.54 +/- 0.04 (P <
      0.05). The RDAs significantly under-predicted the energy requirements of the
      young group (P < 0.05), but there was no significant underprediction in the older
      group. Although obtained in a relatively small number of subjects, these results
      provide no evidence to indicate that the current RDAs underestimate the energy
      requirements of older women, in contrast with previous observations of an
      underestimation of energy requirements by the RDAs in older men.

PMID- 7625341
TI  - Exercise enhances dietary compliance during moderate energy restriction in obese
      women.
AB  - The effect of aerobic exercise on dietary compliance was assessed in 13 obese
      women (44 +/- 3% fat) during a 12-wk weight-reduction program (EX group).
      Seventeen obese women (45 +/- 5% fat) not engaged in aerobic exercise (NX group)
      served as control subjects. The reducing diets were designed to promote a weight
      loss of 1 kg/wk, with energy intakes individually prescribed (mean +/- SD: 4.9 +/
      0.6 MJ/d) to approximate 75% of each subject's measured basal metabolic rate.
      The EX group completed of three 45-min sessions/wk of supervised aerobic exercise
      at 65% of maximal oxygen consumption (VO2max). Daily energy intakes were
      calculated by summing changes in body stores, measured by total body water
      isotope dilution, and total daily energy expenditure, measured by doubly labeled
      water (DLW). Dietary compliance was assessed by comparing calculated intakes with
      prescribed intakes. Both the EX and NX groups reported consuming close to their
      prescribed daily intakes, with differences of -0.08 +/- 0.28 (EX group) and +0.03
      +/- 0.57 (NX group) MJ/d, respectively. However, expenditure/balance data
      determined by the DLW method indicated that the EX subjects exhibited better
      dietary compliance than the NX subjects, with intakes exceeding those prescribed
      by only 0.7 +/- 1.5 compared with 2.3 +/- 1.6 MJ/d for the NX subjects (P =
      0.01). Therefore, an additional benefit of aerobic exercise during energy
      restriction is enhanced dietary compliance, which has important implications for
      the treatment of moderate obesity.

PMID- 7625342
TI  - Relation of weight loss to changes in serum lipids and lipoproteins in obese
      women.
AB  - Several reports have suggested that modest weight losses, as little as 10% of
      initial weight, are sufficient to control many of the health complications of
      obesity. This study examined the relation between changes in weight and those in
      serum lipids and lipoproteins in obese women who participated in a 48-wk weight
      reduction study. Subjects were 66 obese women who were prescribed a 3870-kJ (925
      kcal)/d diet for the first 16 wk and a balanced-deficit diet of 5029-6279 kJ
      (1200-1500 kcal)/d thereafter. Anthropometric measures were assessed at baseline
      and weeks 8, 24, and 48, as were serum triacylglycerols (triglycerides), total
      cholesterol, and low-density-lipoprotein- and high-density-lipoprotein
      cholesterol concentrations. Weight decreased 11.1% during the first 8 wk, during
      which time triacylglycerols and total cholesterol fell 22.7% and 15.7%,
      respectively. Subjects lost an additional 4.7 kg (equal to a total reduction of
      16.4%) between weeks 8 and 24 but triacylglycerols and total and low-density
      lipoprotein cholesterol increased by 5.2%, 4.2%, and 4.5%, respectively during
      this time. Multiple-regression analyses showed that at no time did weight loss
      account for > 6% of the variance in the reductions in triacylglycerol and
      cholesterol concentrations. These findings indicate that modest weight losses are
      associated with significant improvements in serum lipids, but that factors
      including the energy and macronutrient content of the diet prescribed contribute
      significantly to the improvements observed.

PMID- 7625343
TI  - What is the safe protein-energy ratio for infant formulas?
AB  - Infants eat primarily to satisfy energy needs and the safe amount of protein in
      infant formulas (ie, the amount adequate for nearly all infants) is therefore
      expressed as the protein-energy ratio. We studied male infants aged 8-112 d fed
      milk-based formulas. One group (experimental group) was fed formulas that
      provided protein-energy ratios of 3.73 g/MJ (1.56 g/100 kcal) from 8 to 27 d of
      age, gradually decreasing to 2.99 g/MJ (1.25 g/100 kcal) from 84 to 111 d of age.
      Growth rates and serum albumin and urea nitrogen of these infants were compared
      with those of a concurrently studied control group and a previously studied large
      reference group. Gains in weight and concentrations of serum albumin of the three
      groups were not significantly different. Gains in length were significantly less
      for the experimental group than for the reference group. Serum urea nitrogen was
      significantly less in the experimental group than in the control group or
      reference group. We conclude that the protein-energy ratios of the experimental
      formula diet were below the safe level. Because the decrease in growth rate of
      the experimental group was rather small (demonstrable only in comparison with the
      large reference group), and because serum albumin of the experimental group
      increased with age as in normally nourished infants, we suspect that the safe
      protein-energy ratio of infant formulas lies closer to the ratios fed to the
      experimental group than to the ratio [approximately 5.0 g/MJ (2.1 g/100 kcal)] in
      currently marketed milk-based formulas.

PMID- 7625344
TI  - Protein requirements of marginally nourished lactating women.
AB  - Few experimental data regarding protein requirements of lactating women are
      available. This study was designed to determine the protein requirement of seven
      healthy lactating women from a poor Mexican community who were 2-6 mo postpartum
      and had a mean body mass index of 21.8 +/- 2 kg/m2. Nitrogen balances were
      performed at intakes of 0.8, 1.0, and 1.2 g.kg body wt-1.d-1 of a mixed protein
      diet (70% derived from vegetable sources). A balance at 1.2 g.kg body wt-1.d-1 of
      a high-quality mixed protein (80% from animal sources) was the reference. The
      experimental diets were designed to resemble the habitual diet in terms of energy
      and macronutrients. The balance responses to nitrogen intake were -35.5 +/- 12.6,
      -10.5 +/- 14.8, and 7.8 +/- 19.2 mg N.kg body wt-1.d-1, respectively. Equilibrium
      balance was attained at 178.9 +/- 25.8 mg N (1.1 g protein.kg body wt-1.d-1),
      close to current recommended dietary allowances, albeit the dietary protein was
      mostly from vegetable sources.

PMID- 7625345
TI  - Breast-feeding duration and growth of fully breast-fed infants in a poor urban
      Chilean population.
AB  - The duration of breast-feeding and the growth of fully breast-fed infants during
      the first year of life were analyzed according to sex, birth weight,
      characteristics of the mother, and breast-feeding pattern. All infants (n = 1217)
      were healthy and fully breast-fed at 30 d postpartum and 63% and 24% were still
      fully breast-fed at 6 and 12 mo, respectively. The median ages at introduction of
      nondairy food and of milk supplements were 6.0 and 7.4 mo, respectively. The
      probability of remaining fully breast-fed for 12 mo was significantly higher in
      infants with higher birth weight and higher maternal weight, and in infants who
      breast-fed seven times a day or more in the first 6 mo. The comparison of the
      monthly weight and length of fully breast-fed infants with the World Health
      Organization/National Center for Health Statistics reference data showed the
      adequacy of breastfeeding to support infant growth. When mothers and infants are
      healthy, breast milk is sufficient to support adequate infant growth and health
      during the first months of life. The main variables that affect the duration of
      breast-feeding, nutrition and suckling frequency, are susceptible to
      interventions by health services. The results reinforce the need to care for
      maternal nutrition during pregnancy and to provide the support that women need to
      sustain a high suckling frequency.

PMID- 7625346
TI  - Postpartum folic acid supplementation of adolescents: impact on maternal folate
      and zinc status and milk composition.
AB  - The objectives of the present study were to assess the impact of lactation on the
      folate status of adolescents and determine the effect of ingestion of a low-dose
      postpartum (PP) folic acid supplement on maternal folate and zinc status and milk
      composition. Pregnant adolescents (aged 14-19 y; n = 71) were recruited; those
      who initiated breast-feeding on delivery were randomly assigned to a folic acid
      supplement lactating (SL; 300 micrograms/d, n = 14) group or to a placebo
      lactating (PL; n = 15) group. Subjects who initiated formula feeding were given a
      placebo (FF; n = 18). Dietary intakes (two 24-h recalls) were recorded and blood
      and milk samples were collected at 4, 8, and 12 wk PP. Of the adolescents, 71%,
      48%, 67%, and 60% had folate, iron, vitamin B-12, and zinc intakes, respectively,
      below their predicted requirements. Despite this, most blood indexes were within
      normal ranges, probably reflecting the subjects' use of supplements during
      pregnancy. Red blood cell (r = -0.49, P < 0.05) and plasma (r = -0.42, P = 0.08)
      folate concentrations were negatively correlated with milk zinc concentrations.
      Mean red blood cell folate content declined between 4 and 12 wk PP among PL (31%)
      and FF (34%) subjects (P < 0.05) but not among SL subjects. Hence, 300 micrograms
      folic acid/d was sufficient to prevent a decline in blood folate values of these
      adolescents PP.

PMID- 7625347
TI  - Effect of phosphorus supply on mineral balance at high calcium intakes in very
      low birth weight infants.
AB  - To evaluate the effect of varying phosphorus intake with constant high calcium
      intake (430 micrograms/kJ, or 180 mg/100 kcal), we randomly assigned 35
      appropriate-for-gestational-age healthy male infants (birth weight, 715-1510 g)
      on day 21 postnatally to either standard-phosphorus (215 micrograms/kJ, or 90
      mg/100 kcal), moderate-phosphorus (254 micrograms/kJ, or 106 mg/100 kcal), or
      high-phosphorus intake (287 micrograms/kJ, or 120 mg/100 kcal). Three-day mineral
      balances were determined after 7 d of the study diets. Weight and head
      circumference gain and intake of energy and vitamin D were not different for all
      groups. Calcium retentions were sufficient to meet intrauterine accretion in all
      groups. Phosphorus calculated to be available for soft tissue was significantly
      higher in the moderate- and high-phosphorus groups, and was sufficient to support
      soft tissue phosphorus accretion in these two groups. Total absorbed phosphorus
      and phosphorus tubular reabsorption were each affected by phosphorus intake. We
      conclude that very low birth weight infants fed high calcium may require greater
      phosphorus intake than that provided by formulas containing a ratio of calcium to
      phosphorus of 2:1. We suggest that the optimal mass ratio of calcium to
      phosphorus for formula for very low birth weight infants is from 1.6:1 to 1.8:1.

PMID- 7625348
TI  - Polyunsaturated fatty acids result in greater cholesterol lowering and less
      triacylglycerol elevation than do monounsaturated fatty acids in a dose-response
      comparison in a multiracial study group.
AB  - Cholesterol-lowering effects of polyunsaturated and monounsaturated fatty acids
      were compared as they were varied in a reciprocal dose-dependent fashion in the
      context of a National Cholesterol Education Program (NCEP) Step 1 diet. The study
      population comprised 63 moderately hypercholesterolemic African American and
      white men and women. After a 6-wk baseline diet containing 37% of energy from
      total fat and 15% from saturated fat, participants consumed four diets for 6 wk
      each, in random order, containing 10% of energy as saturated fatty acids; 3%, 6%,
      10%, and 14% of energy as polyunsaturated fatty acids; and 17%, 14%, 10%, and 6%
      of energy as monounsaturated fatty acids. Dietary cholesterol, fiber, plant
      sterol, and squalene contents were constant with all four diets. There was a
      progressive decrease in total (P = 0.028) and low-density-lipoprotein cholesterol
      (P = 0.184) across the four diets, with the greatest decrease observed in the
      diet with the highest content of polyunsaturated fatty acids; a small but
      significant decrease in high-density-lipoprotein (HDL) cholesterol that did not
      show a trend between the polyunsaturated and monounsaturated diets; and a trend
      between the four diets in triacylglycerol elevations (P = 0.029), with the
      smallest increment occurring in the diets highest in polyunsaturates. The
      magnitude of the cholesterol-lowering response was greater in those with higher
      baseline cholesterol and less in those who were more obese. The dietary response
      was similar in both ethnic groups and in both sexes. In conclusion, in an NCEP
      Step 1 diet containing 30% total fat, with all other known cholesterol
      influencing dietary factors held constant, the substitution of polyunsaturated
      fatty acid for monounsaturated fatty acid from 3% to 14% resulted in a
      progressive decline in total cholesterol and less triacylglycerol elevations,
      without effect on HDL cholesterol.

PMID- 7625349
TI  - Ileal recovery of starch from whole diets containing resistant starch measured in
      vitro and fermentation of ileal effluent.
AB  - Six subjects with ileostomies consumed five diets containing 61-164 g starch/d of
      which 0.4-34.8 g was resistant starch (RS). Ileal excretion of starch was 97% of
      that measured as dietary RS in vitro with no significant difference between RS
      fed and starch recovered on any of the test diets. Variation in starch excretion
      between subjects was partly due to differences in mouth-to-stoma transit time. In
      vitro fermentation of ileal effluent from RS-supplemented diets produced
      significantly more short-chain fatty acids, a higher molar proportion of butyrate
      (17% compared with 12%), and a lower concentration of ammonia compared with
      control subjects. These results indicate that the amount of starch that reaches
      the large intestine can be predicted from measurements in vitro for a wide range
      of RS intakes under normal eating conditions. They also support the hypothesis
      that RS, through fermentation, has distinctive influences on the colonic
      environment.

PMID- 7625351
TI  - Urinary calcium, sodium, and bone mass of young females.
AB  - Calcium is an important determinant of peak bone mass in young adults because of
      its influence on skeletal development during growth. Attainment of maximum peak
      bone mass requires optimal positive balance between calcium intake and obligatory
      losses of calcium, primarily in urine and feces. Urinary excretion is an
      important determinant of calcium retention in the body. Accordingly, the purpose
      of this study was to evaluate the influence of various nutrients on urinary
      calcium excretion, and to assess their impact on bone mass of young females, aged
      8-13 y, during early puberty. The study was conducted in 381 healthy white
      females in pubertal stage 2. From each participant we collected basic
      anthropometric measurements, a 3-d food record, blood, a 24-h urine sample, and
      bone mass measurements of the total body and forearm by dual X-ray
      absorptiometry. Urinary sodium was found to be one of the most important
      determinants of urinary calcium excretion: [urinary calcium (mmol/d) = 0.01154 x
      urinary sodium (mmol/d) + 0.823], whereas calcium intake had relatively little
      impact: [urinary calcium (mmol/d) = 0.02252 x calcium intake (mmol/d) + 1.5261].
      Urinary calcium was much higher at a calcium intake of approximately 37.5 mmol/d
      (1500 mg/d), supporting the notion that calcium is a threshold nutrient. Calcium
      intake had a significant positive influence on the bone mineral content and
      density of the whole body and radius shaft whereas urinary calcium had a negative
      influence, presumably by reducing calcium accretion into the skeleton.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7625350
TI  - Effects of low-copper diets on human immune response.
AB  - We examined the effects of low-copper diets on indexes of immune response of 11
      healthy men (aged 21-32 y) during a 90-d metabolic suite study. Daily copper
      intake for the first 24 d, next 42 d, and the last 24 d of the study was 0.66,
      0.38, and 2.49 mg, respectively. Feeding the diet with 0.38 mg Cu/d was
      associated with a significant (P < or = 0.05) decrease in the proliferation of
      peripheral blood mononuclear cells cultured with phytohemagglutinin, Concanavalin
      A, or pokeweed, and an increase in the percentage of circulating B cells (CD
      19+), but had no effect on the concentration of serum interleukin 2 receptor, the
      percentage of peripheral monocytes, neutrophils, CD3+, CD4+, or CD8+ T cells; or
      on the neutrophil phagocytic activity. Feeding 2.49 mg Cu/d for 24 d prevented
      further decreases in the indexes affected by the low-copper diet but did not
      restore them to the prestudy concentrations, even though plasma copper and
      ceruloplasmin concentrations were restored to normal.

PMID- 7625352
TI  - Long-term effects of a high-carbohydrate diet and exercise on insulin action in
      older subjects with impaired glucose tolerance.
AB  - Carbohydrate metabolism was assessed in 20 glucose-intolerant subjects before and
      after 12 wk on a high-carbohydrate diet (HC) or the diet combined with exercise
      training (HC-EX). The diet provided 60% of energy as carbohydrate and 20% as fat.
      Neither treatment altered fasting glucose or insulin concentrations or their
      response to a meal. During a glucose clamp (216 pmol insulin/L) glucose disposal
      increased from 13.2 +/- 0.83 to 14.6 +/- 0.83 mumol.kg fat-free mass-1.min-1 (P <
      0.05) in both groups. During more pronounced hyperinsulinemia (654 pmol/L)
      glucose disposal did not change significantly (49.9 +/- 3.8 to 50.7 +/- 3.8
      mumol.kg fat-free mass-1.min-1). Muscle glycogen increased in the HC-EX group
      (78.5 +/- 8.1 to 161.1 +/- 15.7 mmol glucose/kg muscle), with no changes in the
      HC group. These results do not support the recommendation to increase the dietary
      carbohydrate content for improving postprandial glucose metabolism or insulin
      action in glucose-intolerant adults unless combined with exercise training, which
      promotes muscle glycogen storage.

PMID- 7625353
TI  - Accreditation and certification: the rationalization of obesity-management
      services.

PMID- 7625354
TI  - Is there a long-term effect of iron supplementation on anemia alleviation?

PMID- 7625356
TI  - Hypothalamic control of gastric motility.

PMID- 7625355
TI  - Methods of plasma fibrinogen measurement and dietary modification.

PMID- 7625357
TI  - Dietary recommendations for children.

PMID- 7625358
TI  - The need for physician nutrition specialists.

PMID- 7625359
TI  - Training physician nutrition specialists: a fellow's perspective.

PMID- 7625360
TI  - Genetics of responsiveness to high-fat and high-cholesterol diets in the mouse.
AB  - The natural variation among inbred strains of mice was used to elucidate the
      genetic factors underlying the responsiveness to high-fat and high-cholesterol
      diets. The nine strains examined are the progenitors of recombinant inbred strain
      sets: C57BL/6J, C57L/J, SWR/J, SJL/J, SM/J, A/J, AKR/J, C3H/HeJ, and DBA/2J.
      Plasma lipids, liver lipids, the prevalence of cholesterol gallstones, and the
      size of aortic fatty streak lesions were examined after 18 wk of consumption of
      the diet containing 15% fat and 1% cholesterol. The variation in aortic lesions
      found among inbred strains provided the basis for several additional studies that
      demonstrated the existence of eight genes affecting atherosclerosis. These genes,
      named Ath1 to Ath8, are briefly described. The genetic analysis of variation in
      gallstone formation demonstrated that more than one gene affects this phenotype.

PMID- 7625361
TI  - Dietary polyunsaturated fat modifies low-density lipoproteins and reduces
      atherosclerosis of nonhuman primates with high and low diet responsiveness.
AB  - We tested the hypothesis that an increased content of n-6 polyunsaturated fatty
      acids (principally linoleic acid) in an atherogenic diet of nonhuman primates
      would decrease atherosclerosis by modifying the composition and decreasing the
      concentration of plasma low-density lipoprotein (LDL). A species readily
      susceptible to diet-induced atherosclerosis (cynomolgus monkey) was compared with
      a less-susceptible species (African green monkey) with dietary cholesterol
      concentration and saturated or polyunsaturated fat (40% of energy) as variables.
      In both species, cholesterol concentrations in whole plasma, LDL, and high
      density lipoprotein (HDL) were 20-30% lower when polyunsaturated fat was fed,
      whereas dietary cholesterol increased LDL cholesterol three- to fourfold. LDL was
      enriched in cholesteryl oleate when saturated fat and cholesterol were fed.
      Dietary linoleic acid prevented cholesteryl oleate enrichment and promoted
      cholesteryl linoleate accumulation in LDL. At the same plasma cholesterol
      concentration, cynomolgus monkeys had higher LDL cholesterol and lower HDL
      cholesterol concentrations than did African green monkeys. LDL particle size was
      significantly (P < 0.001) larger in the group of cynomolgus monkeys fed
      polyunsaturated fat but tended to be smaller in African green monkeys fed
      polyunsaturated fat. Dietary polyunsaturated fat protected against coronary
      artery atherosclerosis in both species. Thus, LDL particle size, per se, was not
      atherogenic; instead, coronary artery atherosclerosis and cholesteryl oleate
      enrichment of LDL were more highly correlated. This outcome suggests that
      information about LDL composition may be more important for understanding the
      pathogenesis of atherosclerosis than previously suspected.

PMID- 7625362
TI  - Review of human studies evaluating individual dietary responsiveness in patients
      with hypercholesterolemia.
AB  - Individual variation in the low-density-lipoprotein (LDL)-cholesterol response to
      a cholesterol-lowering diet has been well documented in inpatient and outpatient
      diet studies. This variation could be due to both clinical and biological
      factors. Clinical factors include adherence to dietary changes and changes in
      body weight. Biological factors include specific changes in dietary composition,
      initial serum cholesterol concentrations, presence of excess body weight, the
      fractional catabolic rate of LDL with a diet high in saturated fatty acid, the
      presence of specific isoforms of apoprotein E and apoprotein A-IV, changes in the
      gene encoding apoprotein B or the apoprotein A-I promoter region, and the
      ultracentrifugation pattern of LDL lipoproteins. Work exploring the metabolic
      basis for individual variation in responsiveness to a cholesterol-lowering diet
      is in its infancy. Careful studies controlling for the clinical influences of
      responsiveness are needed so that true biological determinants of response can be
      uncovered.

PMID- 7625364
TI  - Effects of sex and ethnicity on responses to a low-fat diet: a study of African
      Americans and whites.
AB  - The effects of sex and ethnicity on plasma lipoprotein changes that occur with
      low-fat diets were studied in 34 African American subjects (20 women, 14 men) and
      29 white subjects (13 women, 16 men) aged 25-62 y with moderate
      hypercholesterolemia. A baseline diet containing 37% fat (15% saturated) was
      compared with four experimental diets containing 30% fat (10% saturated) with
      reciprocally varying contents of polyunsaturated and monounsaturated fatty acids.
      Diets were fed for 6 wk each, and all food and beverages provided and compliance
      were intensively monitored. Body weight and physical activity were held constant.
      Lowering of total and low-density-lipoprotein cholesterol were similar between
      women and men and between African Americans and whites. Small differences were
      observed between women and men in the extent of high-density lipoprotein lowering
      and triacylglycerol elevations. Additionally, African American subjects had
      slightly higher triacylglycerol elevations than did white subjects. Results
      suggest that men and women of varied ethnic backgrounds should respond similarly
      to cholesterol-lowering diets. Studies are required to develop strategies for
      achieving dietary changes that consider diverse eating patterns and cultural
      barriers to dietary adherence.

PMID- 7625363
TI  - Low-density-lipoprotein subclasses and response to a low-fat diet in healthy men.
AB  - Lipid and lipoprotein responses to reduced dietary fat intake were investigated
      in relation to differences in distribution of low-density-lipoprotein (LDL)
      subclasses among 105 healthy men consuming high-fat (46% fat) and low-fat (24%
      fat) diets in random order for 6 wk each. With high-fat diets, 87 subjects had
      predominantly large, buoyant LDL (pattern A), whereas the remainder had primarily
      smaller, denser LDL (pattern B). With low-fat diets, 36 men changed from pattern
      A to B. Compared with the 51 men with pattern A with both diets (stable A group),
      men in the stable B group (n = 18) had significantly greater reductions in plasma
      LDL cholesterol, apolipoprotein B, and mass of mid-sized (LDL II) and small (LDL
      III) LDL subfractions. In both the stable A and change groups, there was a shift
      in LDL particle mass from larger, lipid-enriched (LDL I and II) to smaller, lipid
      depleted (LDL III and IV) subfractions, suggestive of change in LDL composition
      with minimal change in particle number, and consistent with the observation of
      reduced plasma LDL cholesterol without reduced apolipoprotein B. Stable B
      subjects had significantly greater increases in the largest very-low-density
      lipoprotein subfraction with the low-fat diet than the stable A group, and also
      had greater decreases in the high-density-lipoprotein (HDL) subclass HDL3 but
      smaller reductions in HDL2. Genetic and environmental factors influencing LDL
      subclass distributions thus may also contribute substantially to interindividual
      variation in plasma lipoprotein response to a low-fat diet.

PMID- 7625365
TI  - Adjuvant postoperative radiotherapy for adenocarcinoma of the rectum and
      rectosigmoid. A retrospective analysis of locoregional control, survival, and
      prognostic factors on 178 patients.
AB  - Results are presented of a retrospective study on 178 patients receiving adjuvant
      postoperative radiotherapy after curative surgery for adenocarcinoma of the
      rectum and rectosigmoid. Tumorstages according to Gunderson-Sosin were B2: 67,
      B3: 5, C1: 9, C2: 94, and C3: 3. Median total dosage was 50 Gy (range: 10-66 Gy),
      with a median dose per fraction of 2.0 Gy, 5 fractions per week. The censored
      overall 5-year survival rate was 42%, and 5-year disease-free survival rate was
      37%. The respective rates for stage B2 patients (n = 67) were 59% and 53%, and
      for stage C2 patients (n = 94), 25% and 25%. Recurrences occurred in 89% within 3
      years, 8% in the fourth, and 1% in the fifth year of follow-up. Five-year local
      relapse rates were 27% for the stage B2 tumors and 40% for the stage C2 tumors.
      For survival, stage (P = .006), grade (P = .02), fixation at surgery (P = .03),
      and gender (P = .03) were independent prognostic factors. With local relapse-free
      probability (LRFP) as endpoint, grade (P < .02) was an independent prognostic
      factor. Dose of radiation was not of prognostic significance, neither for
      survival (P = .63) nor for LRFP (P = .61). Since improvement should be made in
      locoregional control, initiatives are taken to start preoperative radiotherapy;
      furthermore, the key role of surgery is emphasized.

PMID- 7625366
TI  - Impact on progression-free survival of adjuvant cyclophosphamide, vincristine,
      doxorubicin (adriamycin), and dacarbazine (CYVADIC) chemotherapy for stage I
      uterine sarcoma. A prospective trial.
AB  - To assess the impact on progression-free survival of the use of the multiagent
      chemotherapy regimen of cyclophosphamide, vincristine, doxorubicin (Adriamycin),
      and dacarbazine (CYVADIC) as adjuvant treatment for patients with stage I uterine
      sarcoma: 20 evaluable patients who underwent total abdominal hysterectomy and
      bilateral salpingo-oophorectomy for stage I uterine sarcoma received adjuvant
      multiagent chemotherapy with vincristine sulfate 1 mg/m2 days 1 and 4,
      doxorubicin (Adriamycin) 40 mg/m2 and cyclophosphamide 400 mg/m2 day 2, and
      dacarbazine 200 mg/m2 days 1 through 4 for a total of 9 monthly cycles or until
      recurrence of disease was documented. Patients were followed for a median of 65
      months (range: 5-116 months). Myelotoxicity was monitored by weekly complete
      blood counts, cardiac toxicity by monthly radionuclide angiography, and
      neurotoxicity by monthly physical examination. Survival and progression-free
      survival were calculated by the method of Kaplan and Meier (17). The Fisher exact
      test was employed to determine the significance of recurrence rates between
      histologic groups (18). These 20 patients received 172 of a planned 180 cycles of
      chemotherapy. Dose reductions in response to myelotoxicity were necessitated in
      four cycles among three patients. Mild neurotoxicity was observed in six patients
      (30%) and moderate neurotoxicity in one patient (5%). A decrease in cardiac
      ejection fraction of > 10% was observed in two patients (10%). No deaths
      ascribable to complications arising from chemotherapy were observed. Seven
      patients (35%) developed recurrence of disease. Recurrence rates for pure
      sarcomas and mixed mesodermal tumors did not differ significantly (P = .65).
      Progression-free survival for the population at 2 years was 80% and at 5 years
      was 65%. This study describes the largest prospective trial of adjuvant
      combination chemotherapy for patients with stage I uterine sarcoma reported to
      date. Adjuvant chemotherapy employing the combination of cyclophosphamide,
      vincristine, doxorubicin (Adriamycin), and dacarbazine (CYVADIC) failed to impact
      significantly on long-term survival in this group of patients with stage I
      uterine sarcoma.

PMID- 7625367
TI  - Hepatocellular carcinoma. An ECOG randomized phase II study of beta-interferon
      and menogaril.
AB  - This study was undertaken to investigate the response rate, time to treatment
      failure and survival time of patients with hepatocellular cancer (HCC) treated
      with beta-interferon or menogaril. Sixty-nine patients with histologically
      confirmed, advanced, measurable hepatocellular carcinoma were randomized to
      receive beta-interferon or menogaril. Eligibility criteria included an Eastern
      Cooperative Oncology Group (ECOG) performance status of 0, 1, 2, or 3, as well as
      adequate kidney and liver function and hematologic reserve. The number of
      patients with lethal, life-threatening, and severe toxicities on beta-interferon
      were 1, 3, and 12 and on menogaril 2, 5, and 10, respectively. No objective
      responses were documented among the 61 patients who had HCC, histologically
      reviewed and confirmed. The time to treatment failure was 6.7 weeks on beta
      interferon and 8.6 weeks on menogaril. The median survival time was 11.1 weeks on
      beta-interferon and 23.1 weeks on menogaril (South African patients 10.1 weeks).
      The difference is not significant. Poor prognostic factors were jaundice, age,
      and associated hepatitis. After controlling for other covariates, beta-interferon
      appears to increase the relative risk of dying by 2.7. This trial reconfirms the
      importance, previously reported by ECOG of jaundice and age in the prognosis of
      patients with HCC. It shows that further trials with neither beta-interferon nor
      menogaril are warranted.

PMID- 7625368
TI  - Vinorelbine plus cisplatin in recurrent or previously untreated unresectable
      squamous cell carcinoma of the head and neck.
AB  - Despite considerable progress achieved in the management of head and neck
      carcinomas (HNC) in the last decade, the prognosis of patients with advanced
      squamous cell HNC is still dismal. On the basis of the reported good activity of
      a new vinca alkaloid derivative, i.e., vinorelbine (VNR), we tested the
      combination of cisplatin and VNR in a series of patients with recurrent or
      previously untreated unresectable squamous cell HNC. Thirty-five patients with
      recurrent or previously untreated unresectable squamous cell HNC were treated
      with a combination of cisplatin 80 mg/m2 on day 1, plus vinorelbine 25 mg/m2 i.v.
      push on days 1 and 8. This cycle was repeated every 3 weeks. Analysis of response
      rates was carried out separately for previously untreated patients, and those
      with recurrent disease after surgery and/or radiotherapy. In the group of 20
      patients with recurrent disease the overall response rate was 55% (95% CL 44
      66%), with 3 patients (15%) showing a complete response with a mean duration of
      6.2+ months and 8 patients showing a partial response with a mean duration of
      8.6+ months. In the group of patients with previously untreated unresectable
      disease, 13 patients (87%, 95% CL 78-96%) had a major objective response with a
      complete response rate of 27%. This regimen was quite well tolerated, with
      meyelosuppression and vomiting being the most frequent toxicities. The occurrence
      of an acute pain syndrome following vinorelbine administration in 4 patients is
      noteworthy. In conclusion, this combination is active in advanced squamous cell
      head and neck carcinoma. However, although it may be recommended in recurrent
      carcinoma, the complete response rate achieved in previously untreated patients
      is lower than that reported with other more intensive regimens.

PMID- 7625369
TI  - Results of irradiation in patients with high-grade gliomas evaluated by magnetic
      resonance imaging.
AB  - Evidence shows that most high-grade gliomas are a diffuse process. Prior studies
      reported a median survival with surgery and postoperative radiotherapy of 8.6
      months for glioblastoma multiforme (GBM) and 36.2 months for anaplastic
      astrocytoma (AA). Since MRI delineated the glioma better than CT scan, using MRI
      based radiotherapy treatment planning allows for more precise treatment volumes.
      We retrospectively reviewed the records of the first 36 patients with malignant
      glioma, who had a presurgery MRI-based radiotherapy treatment planning. These
      patients were diagnosed between January 1986 and February 1991. Minimum follow up
      was 14 months and median survival was 15.4 months for GBM (7-42 months) and 27.4
      months for AA (7-53 months). We feel that the trend for increased median survival
      in GBM (15.4 vs 8.6 months) is partly due to better definition of the tumor
      volume by using MRI. Larger studies are needed to confirm this finding.

PMID- 7625370
TI  - Cisplatin and chronic oral etoposide as salvage therapy for advanced colorectal
      carcinoma.
AB  - Patients with metastatic colorectal carcinoma who have failed 5-fluorouracil
      based chemotherapy have no effective second-line treatment available. Recent
      studies demonstrating clinical synergy between cisplatin and etoposide, and
      others exploring the efficacy of etoposide regimens utilizing chronic oral
      administration, suggested the utility of a new regimen incorporating these
      elements to treat refractory colorectal carcinoma. Fourteen patients were treated
      with weekly cisplatin and daily oral etoposide for 21 days in cycles of 28-35
      days. Toxicity was significant, both hematologic and gastrointestinal in these
      pretreated patients. There were no objective responses, and median survival was
      9.5 months. Weekly cisplatin and daily oral etoposide are poorly tolerated and
      ineffective in the treatment of refractory colorectal carcinoma. Further studies
      are needed to discover effective therapy for this disease.

PMID- 7625371
TI  - Ifosfamide plus high-dose cisplatin in patients with non-small cell lung cancer
      previously treated with chemotherapy.
AB  - This study determined the maximum tolerated dose (MTD) of ifosfamide that could
      be given with high-dose cisplatin to non-small cell lung cancer (NSCLC) patients
      previously treated with non-platin-containing chemotherapy and to assess the
      efficacy of this combination. Twenty-three patients with inoperable NSCLC treated
      with one prior chemotherapy regimen received continuous infusion ifosfamide 1.2
      g/m2 per day with MESNA for 5 days every 35 days and cisplatin 120 mg/m2. After
      one patient who received cisplatin as a single dose developed grade 4
      nephrotoxicity and myelosuppression, cisplatin was given in four divided doses
      (30 mg/m2 per day) and the ifosfamide dose was lowered to 1.0 g/m2 per day,
      infused over 4 days. Dose-limiting grades 3 and 4 leukopenia was seen in 43%. A
      major objective response rate of 9% was observed. The 1-year survival was 30%,
      with a median survival of 6.4 months. The MTD of ifosfamide administered with
      cisplatin (30 mg/m2 per day for 4 consecutive days) to this population of
      patients is 1.0 g/m2 daily for 4 days. This combination produced limited
      anticancer activity and significant toxicity. Excessive toxicity was observed
      when cisplatin was given as a single dose with ifosfamide, and this schedule
      should not be used.

PMID- 7625372
TI  - Phase I study of monoclonal antibody-ricin A chain immunoconjugate Xomazyme-791
      in patients with metastatic colon cancer.
AB  - The immunoconjugate XMMCO-791/RTA consists of ricin A chain bound to a murine
      monoclonal antibody MoAb 791T. This monoclonal antibody (MoAb) binds to a
      glycoprotein of 72 kD, which is expressed on human colorectal carcinoma, ovarian
      carcinoma, and osteogenic sarcoma. XMMCO-791/RTA was tested in a Phase I trial
      with proposed dose escalation steps of 0.02, 0.04, 0.15, and 0.2 mg/kg per day.
      Twelve patients with metastatic colorectal carcinoma were treated at 0.02, 0.03,
      and 0.04 mg/kg per day dose levels administered over 1 hour on days 1-5. Study
      related toxicities were hypotension (6 patients); greater than 10% weight gain (6
      patients); peripheral edema (9 patients); fever (4 patients); confusion (3
      patients); diarrhea (3 patients); proteinuria, as identified by dipstick (3
      patients), greater than 0.6 mg/dl decrease in serum albumin (11 patients);
      greater than 25% decrease in oncotic pressure (10 patients), and a decrease in
      ionized calcium (8 patients). Six patients received a second course of treatment.
      HAMA levels developed in 9 patients and titers increased with number of courses
      administered. Decreased overall toxicity, in comparison to the first course, was
      noted, but one patient had an allergic-type response (hypotension, crushing chest
      pain, diaphoresis) after the test dose of the second course (HAMA level > 10,000
      IgG). Life-threatening toxicity in the form of fluid shift, resulting in
      noncardiac pulmonary edema and third-spacing occurred after course 1 in 1 of 3
      patients at the 0.04 mg/kg per day level. No further dose escalation was
      attempted and no antitumor activity was seen.

PMID- 7625373
TI  - Phase II trial of etoposide, doxorubicin, and cisplatin combination in advanced
      measurable gastric cancer. An Eastern Cooperative Oncology Group study.
AB  - A phase II study was performed to determine the efficacy and toxicity of the
      etoposide, doxorubicin, cisplatin (EAP) regimen in the treatment of patients with
      advanced measurable gastric cancer in a multi-institutional cooperative group
      setting. Thirty-one evaluable patients with advanced measurable gastric
      adenocarcinoma were treated with etoposide 120 mg/m2 on days 3, 4, and 5,
      doxorubicin 20 mg/m2 on days 1 and 8, and cisplatin 40 mg/m2 on days 2 and 9. The
      treatment was repeated every 28 days. Objective responses were seen in 7 (23%)
      patients, all achieving partial remissions. Median survival was 9 months for the
      entire group. Toxicity was mostly hematologic, with grade 3 leukopenia in 26% and
      grade 4 leukopenia in 55% of the patients. There were 4 treatment-related deaths
      that were attributable to severe leukopenia and sepsis. Because of the high
      toxicity and moderate response rate, this regimen is not superior to other less
      toxic regimens and cannot be recommended for the treatment of advanced gastric
      cancer outside of an investigational protocol.

PMID- 7625376
TI  - Nasopharyngeal carcinoma. A study examining Asian patients treated in the United
      States.
AB  - From 1972 to 1991, 126 Asian patients with nasopharyngeal carcinoma underwent
      definitive radiation therapy for locoregional disease: 86 men, 40 women. Median
      age was 50. All patients received external-beam irradiation with cobalt 60 or 4
      18 MV x-rays. Local recurrence, regional recurrence, and distant metastases were
      22%, 11%, and 23%, respectively. Local recurrence progressively increased with
      increasing T stage, but doses in those who recurred did not differ from the group
      as a whole. Regional recurrence was not associated with T or N stage or dose.
      Patients with N2 disease had the highest distant metastatic rate. The 5- and 10
      year overall survival rates were 54% and 38%, respectively. Of age, gender, and
      histology, only age less than 50 was found to be favorably prognostic. No severe
      long-term complications were observed, and acute reactions were acceptable. Our
      survival results are comparable with results found both in Asia and North
      America. Nonetheless, altered fractionation techniques and/or other radiation
      modalities should be further explored to improve locoregional control.

PMID- 7625374
TI  - Flow cytometric analysis of nuclear DNA content in the endoscopic biopsy tissues
      of gastric cancer.
AB  - The nuclear DNA content was measured by flow cytometry in gastric cancer patients
      using endoscopically biopsied tissue specimens. When the specimens were
      classified into diploid and aneuploid according to the DNA histogram, 56%
      (65/117) of the specimens were aneuploid, and advanced cancer was clearly more
      often aneuploid than early cancer. The frequency of aneuploidy appeared to be
      higher as the histologic depth of cancer was greater. Noncancerous tissues of the
      stomach were mostly diploid. The nuclear DNA ploidy pattern in gastric cancer
      cells could be analyzed by using endoscopic biopsy samples and this flow
      cytometric investigation would be possibly contributive to further
      characterization of gastric cancer in the diagnostic procedure of malignancy.

PMID- 7625375
TI  - Initial brachytherapy in the breast conservation approach to breast cancer.
AB  - The outcome of 100 consecutive newly diagnosed breast cancer patients treated
      between 1975 and 1985 within a protocol of planned segmental mastectomy and
      radiation therapy that included an initial brachytherapy boost is reported.
      Margins were not routinely inked in this study and the tumor bed was determined
      with the operating surgeon at the time of brachytherapy. There were 30 T1 tumors,
      61 T2, and 9 T3. Segmental mastectomy was followed 2 weeks later by an
      interstitial implant with iridium-192 sources given as initial boost dose to the
      tumor bed, at the time of axillary dissection. All patients received at least 20
      Gy as boost dose followed by external beam radiation to a total dose of 45-50 Gy
      to the breast and regional nodes delivered over a period of 4-5 weeks. With a
      median follow-up of 7 years a total of 3 (3%) breast recurrences were detected
      (1/30 in T1 tumors, 2/61 in T2 tumors). Only one of the three recurrences was at
      the initial tumor bed. None of the nine T3 patients included in this series
      recurred locally. There were 4 severe complications (2 soft tissue necroses and 2
      osteonecroses) occurring in 2/30 T1 and in 2/61 T2. Cosmetic results were good to
      excellent in 77% of the cases and fair to poor in 23%. The actuarial local
      control and survival probability rate were, respectively, 95% and 85% at 5 years
      and 93% and 73% at 10 years. Initial brachytherapy boost to a target volume
      accurately determined with the operating surgeon followed by subsequent external
      beam radiotherapy achieved excellent local control in the breast even for lesions
      larger than 2 cm (70% of the reported cases).

PMID- 7625377
TI  - Cancer of the esophagus following allogeneic bone marrow transplantation for
      acute leukemia.
AB  - The successful development of allogeneic bone marrow transplantation (BMT) has
      markedly improved the treatment results for acute leukemia and other hematologic
      diseases. However, significant complications are associated with this procedure
      including the development of chronic graft versus host disease (GVHD). Treatment
      for this condition requires chronic immunosuppression which can lead to the
      development of second cancers. It is well known that immunosuppression is
      associated with a variety of tumors, most commonly lymphoma. The development of
      solid tumors appears to be less common but follow-up studies of patients treated
      for Hodgkin's disease demonstrate a rising incidence of solid tumor development
      after a delay of 5 to 10 years. We describe a patient recently treated for a
      squamous cell carcinoma of the esophagus which developed 5 years after an
      allogeneic BMT for acute myelogenous leukemia (AML). The patient had been treated
      with immunosuppressants for chronic GVHD. The clinical course is described and
      the literature is reviewed regarding recent experience with the development of
      solid tumors following allogeneic BMT. The majority of second tumors following
      BMT are lymphomas and leukemias. Secondary solid tumors are less common, but the
      incidence appears to increase over time. Squamous carcinomas are most common and
      a preparative regimen combining radiation and chemotherapy may increase risk.
      Careful long-term follow-up of BMT is essential in order to detect second tumors
      at an early stage.

PMID- 7625380
TI  - Combination recombinant interleukin-2, recombinant interferon-alpha, and 5
      fluorouracil for treatment of metastatic renal cell carcinoma.

PMID- 7625379
TI  - The evolving role of brachytherapy in breast cancer.
AB  - The role of brachytherapy in the treatment of carcinoma of the breast continues
      to evolve. Initially, brachytherapy was used alone; later it was used to boost
      external beam irradiation. In the 1980's, its role diminished. Low-energy
      radionuclides like iodine-125 and remote-controlled high-dose-rate brachytherapy
      have been used to reduce radiation exposure to medical care givers. The 1990's
      has seen renewed interest in the use of brachytherapy alone to the tumor for
      management of primary and recurrent breast cancer. Randomized, controlled
      clinical trials are needed to redefine the role of brachytherapy in breast
      cancer.

PMID- 7625378
TI  - Use of perioperative or split-course interstitial brachytherapy techniques for
      salvage irradiation of isolated local recurrences after conservative management
      of breast cancer.
AB  - Treatment of local recurrence after conservative management for breast cancer is
      mastectomy. When mastectomy is contraindicated or refused, could brachytherapy be
      a therapeutic alternative for such isolated local relapses (ILR)? From February
      1977 to June 1990, 38 patients, previously treated by radiation therapy or by a
      combination of radiotherapy and surgery for breast cancer, underwent salvage
      brachytherapy for an ILR. Fifteen patients were treated by limited tumorectomy
      plus 30 Gy perioperative brachytherapy for a 2.4-cm mean diameter IRL (Group A).
      Twenty-three patients were treated by exclusive split-course brachytherapy,
      delivering 60-70 Gy by two implants at 1-month interval, for a 3.9-cm mean
      diameter IRL (Group B). All patients achieved a clinical complete response after
      treatment. With a mean follow-up of 40 +/- 24 months, eight patients (21%)
      experienced local relapse between 9 and 48 months (four patients in Groups A and
      B). This second local recurrence was isolated in one case and was associated with
      metastatic disease in seven cases. At 5 years, overall survival was 55% (61% for
      Group A and and 50% for Group B). Three patients developed local complications
      requiring mastectomy (skin necrosis, two patients; severe breast pain, one
      patient). Cosmetic results in locally controlled patients were good in four
      patients, acceptable in twelve patients, mediocre in nine patients, and
      nonvaluable in two patients. Both perioperative brachytherapy and exclusive split
      course brachytherapy appear to be feasible techniques and may be used
      occasionally as an alternative therapy to radical mastectomy for ILR.

PMID- 7625381
TI  - Oral lesions caused by an orthodontic retainer: a case report.

PMID- 7625382
TI  - A comparison of one-stage and two-stage nonextraction alternatives in matched
      Class II samples.
AB  - In the treatment of Class II malocclusion, an early phase of functional appliance
      treatment is commonly used to simplify subsequent fixed appliance therapy and to
      optimize the development of the facial skeleton. Unfortunately, these
      expectations enjoy little support in the refereed literature. The present study
      therefore was undertaken to examine the benefits of a two-stage bionator/edgewise
      regimen in comparison to the more conventional one-stage edgewise alternative. To
      minimize proficiency bias, we examined the records of the one- and two-stage
      Class II nonextraction patients who received treatment between 1980 and 1990 by a
      single experienced clinician. On the basis of descriptive data from 96 sets of
      initial study models and lateral cephalograms, discriminant analysis was used to
      identify two subsamples of 36 patients who were relatively similar before
      treatment and thus equally susceptible to the two treatments. Of these 72
      "borderline" patients, 19 subsequently underwent a change in treatment plan (to
      extraction or surgery), leaving 25 two-stage and 28 single-stage nonextraction
      patients on whom to base a comparison of treatment effects. Except for a slight
      posttreatment difference in age (and, hence, size), the two groups underwent
      skeletal changes that left them essentially indistinguishable at the end of
      treatment. In both groups, these skeletal changes were largely responsible for
      molar and overjet corrections that were nearly identical in the two groups. The
      rates of change, however, differed significantly. As a result, the two-stage
      treatments started earlier and finished later. Although the present data do not
      address the relative impact of the two strategies on the 10% to 15% at each tail
      of the distribution, the early phase of functional appliance treatment conferred
      no obvious, measurable benefits on the central 75%. Therefore for most
      nonextraction Class II patients, the choice of treatments may well constitute a
      practice management, rather than a biologic, decision.

PMID- 7625383
TI  - Comment on fixed partial denture.

PMID- 7625384
TI  - Microbial attack of orthodontic adhesives.
AB  - Composites used as orthodontic direct bonding adhesives have a polymeric matrix
      that can host and nurture a variety of aerobic and anaerobic microorganisms
      acting alone or in combination (consortia). Their accumulation can lead to the
      weakening of the bond and possibly the attacking of the tooth. A number of
      microorganisms have been identified as present on the removed direct bonding
      brackets. Their action has been duplicated in vitro. Although some are specific
      to the oral environment, others are "opportunistic," i.e., have external sources.
      The results of attempts to detect the origin of the latter suggests a
      contamination of iatrogenic origin. Thus a high percentage of attacked adhesive
      can be traced to specific orthodontic offices, a fact that could be indicative of
      a breach in the sterilization procedures. While the attack of microorganisms on
      orthodontic adhesives is spectacular, less obtrusive inroads are likely to occur
      whenever similar acrylic composites are used in general dentistry, i.e., in
      restorations, veneers, and crowns. Indeed, it has been found that neither these
      polymeric products, nor some of the ingredients used to make them, exhibit a
      bacteriostatic activity, being metabolized instead. Results of rendering the
      adhesive microbe-resistant by adding a bactericide have shown to be encouraging.

PMID- 7625385
TI  - Comment of the effectiveness of an extreme canine-protected splint.

PMID- 7625386
TI  - Impact of orthodontics on the psychologic profile of adult patients: a
      prospective study.
AB  - Considerable controversies exist about the psychologic repercussions of
      malocclusions on affected persons and the positive effect of treatment on
      patients' body image and self-concept. This report describes a longitudinal
      prospective study of 40 adult patients with moderate to severe malocclusions who
      underwent conventional orthodontic treatment. All subjects completed a series of
      psychological questionnaires at three different measurement intervals: (1) before
      the start of treatment, (2) 6 months afterwards, and (3) from 1 to 4 weeks after
      the end of active treatment. For most personality variables including self
      esteem, the mean pretreatment values were normal. Mean values of both overall and
      facial body image were lower than normal and improved significantly after
      treatment. Overall body image improvement was noticeable from 6 months after the
      start of treatment, whereas facial body image did not improve until the
      discontinuation of the orthodontic appliances. Self-esteem did not change over
      time. Changes in some 16PF factors that deserve further analysis were observed.
      The positive effect of orthodontics on body image is encouraging but longer
      follow-up is needed to evaluate the persistence of results and the eventual
      occurrence of any late changes in self esteem.

PMID- 7625387
TI  - The centered T-loop--a new way of preactivation.
AB  - The force system of a prefabricated and preactivated T-loop used for reciprocal
      space closure was determined by simultaneously measuring the horizontal and
      vertical forces, as well as the moments using a computer controlled measuring
      apparatus. Interbracket distances of 21, 24, 27, and 30 mm were used to mimic
      typical clinical situations. At a loop activation of 7 mm, the anterior and
      posterior segments first underwent controlled tipping, then translation, and
      finally, root uprighting as the moment-to-force ratio increased with
      deactivation. After the loop has been deactivated to 4 mm, however, it should be
      exchanged to avoid root abutment.

PMID- 7625388
TI  - Comment on the overuse of surgical procedures.

PMID- 7625390
TI  - Comment on standard of care in private practice.

PMID- 7625389
TI  - Etiologic aspects and orthodontic treatment of unilateral localized arrested
      tooth-development combined with hearing loss.
AB  - In this study a case has been presented involving localized, arrested maxillary
      tooth development, asymmetric maxillary development, and unilateral loss of
      hearing. No similar case seems to have been described before. The orthodontic
      treatment comprised extraction of four permanent tooth germs in the maxilla and
      autotransplantation of mandibular teeth, followed by the use of fixed orthodontic
      appliances and a one-unit bridge restoration. Etiologic aspects are discussed. It
      is suggested that a severe attack of mumps that involved massive swelling of the
      parotid glands immediately after chicken pox and measles at the age of 4 to 5
      years, may have resulted in a neurologic reduction of hearing and arrested tooth
      development. The teeth in which root development in relation to mumps does not
      appear to have been reported previously, whereas hearing loss after mumps has
      been reported. In the search for verification of this possible connection,
      children with arrested tooth development should be examined for reduction of
      hearing, and children with hearing loss after mumps ought to have their dental
      development checked.

PMID- 7625391
TI  - Smile esthetics after orthodontic treatment with and without extraction of four
      first premolars.
AB  - Standardized frontal photographs were taken of the face during smiling for 60
      retention patients; 20 from each of three different private orthodontic
      practices. Thirty patients had been treated with extraction of four first
      premolars, and 30 with full edgewise appliances but no extractions. Smile
      esthetics were judged by a panel of 10 laypersons. There were no significant
      differences in the mean esthetic score of extraction and nonextraction patients.
      The only variable that strongly predicted the esthetics of extraction patients
      was the office in which they were treated, indicating that there may be a
      significant difference among practitioners in the esthetic outcome of four
      premolar extraction treatment. Variables related to the "buccal corridor" or
      other measures of the relationship between the width of the dentition and the
      width of the mouth during a smile showed no relationship to extraction esthetics.
      The results indicate that there is no predictable relationship between the
      extraction of premolars and the esthetics of the smile.

PMID- 7625393
TI  - The surgical uprighting of mandibular second molars.
AB  - The mandibular second molars can become impacted beneath the crown of the first
      molars and fail to erupt normally. A study of 22 cases with follow-up periods of
      at least 18 months shows the results obtained by surgical uprighting of these
      teeth. Of 22 teeth, one has been lost but none of the remaining 21 has developed
      infection or required root treatment, and all are in good occlusion. Six teeth
      give a normal response to electrical pulp testing. In most cases, with judicious
      bone removal, the second molar is firm and stable after uprighting and requires
      no splinting, but in some cases temporary stabilization is required. The bone
      defect normally seen mesially after uprighting reossifies both clinically and
      radiographically.

PMID- 7625392
TI  - Plasticity of craniomandibular muscle function: 31P magnetic resonance
      spectroscopy of the rabbit masseter muscle.
AB  - The masseter muscle was studied during postnatal development of the rabbit from
      the juvenile to adult stage in which the oral function was altered during
      maturation by modifying the diet to soft food. The muscle was assessed using
      phosphate magnetic resonance (31P NMR) spectroscopy with a single-turn copper
      surface coil to study potential changes in phosphate metabolism. The 31P NMR
      spectra consisted of five peaks related to unbound forms of inorganic phosphate
      (Pi), creatine phosphate (PCr), and three peaks related to the adenosine
      triphosphate (ATP). The masseter was assessed in one group of five rabbits at 8
      weeks postnatally (juvenile) and after 4 months of this experimental group
      masticating on soft food. They were compared with a control group of five rabbits
      raised on a normal hard diet. The Pi/PCr ratio increased in the adult masseter
      much higher during twitching, tetany, and periodic contraction than in the
      juvenile regardless as to whether the adult animal had been raised from the
      juvenile period on soft or hard diet. There were relatively few differences
      between the experimental adult animals raised on a soft diet and the normal adult
      animals despite the soft diet animals demonstrating a significantly lower weight
      and smaller muscle mass. These findings suggest that chronic underuse of the
      masseter muscle by decreasing the masticatory loads has a minimal effect on the
      phosphate metabolism of the maturing masseter.

PMID- 7625394
TI  - Changes concurrent with orthodontic treatment when maxillary expansion is a
      primary goal.
AB  - A retrospective study of dental and maxillary skeletal changes occurring during a
      period of orthodontic treatment was made from pretreatment and posttreatment
      dental casts. Sixty maxillary expansion cases were examined. Thirty cases had
      maxillary expansion accomplished with a fixed rapid palatal expander and 30 were
      expanded with a quadhelix appliance. All cases were finished with full fixed
      edgewise appliances. Multiple linear regression analyses were completed for both
      groups with upper molar width change as the criterion and age, tipping of the
      upper molars, palatal width change and maxillary tipping as the predictors. All
      predictors were included in the analysis for the quadhelix group with a
      significant R2 value of 0.55. For the rapid expansion group, a significant R2
      value of 0.33 was achieved with the inclusion of palatal width change and age
      only. The other variables did not meet the level of significance for entry into
      the model. Although both groups demonstrated similar amounts of maxillary dental
      expansion, the rapid expansion group demonstrated greater average skeletal
      expansion. In addition, there was a significant relationship between skeletal and
      dental expansion for the rapid expansion group, but not the quadhelix group.
      Palatal depth increased more on average in the rapid expansion group suggesting
      that there was greater dental eruption in that group. Expansion across the
      mandibular molars was greater on average in the quadhelix group. There was no
      difference in the degree of upper molar rotation or final upper and lower arch
      forms between the two groups.

PMID- 7625395
TI  - Prenatal growth of the human mandibular condylar cartilage.
AB  - The question of whether the condylar cartilage possesses a growth potential like
      that of the long bone growth plates has been the subject of contrasting
      viewpoints. We have recently established that the thickness of the human tibial
      growth plate progressively decreases during the second half of the fetal period,
      but that the changes in the total human condylar thickness do not correlate with
      fetal age or weight. The present study examined the change in the thickness of
      the human mandibular condyle layers during the fetal growth of the mandible.
      Mandibles were obtained from autopsy of 19 human fetuses ranging in fetal age
      from 18 to 41 weeks. The total length of the mandible, the lengths of the
      mandibular body and of the ramus were measured, as well as the gonial angles. The
      total thickness of the condyle, and the thickness of the articular, progenitor,
      cartilage, chondroblast, and hypertrophic chondrocyte layers were measured on the
      central segment of central sagittal sections of the mandibular condylar
      cartilage. The total mandible, the corpus and the ramus lengths increased
      linearly with the age of the fetus and they all correlated strongly with fetal
      weight. However, changes in the total condylar thickness and in the thickness of
      the cartilage layer (chondroblast plus hypertrophic chondrocytes) did not
      correlate with fetal weight or mandibular length. The thickness of the articular
      layer increased with weight, but changes in the progenitor layer were independent
      of corporal and mandibular growth.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7625396
TI  - A case report of a Brodie bite.

PMID- 7625397
TI  - Bonded orthodontic retainers: a review.
AB  - Recent reports have suggested that long-term retention may be required to prevent
      posttreatment changes. The bonded orthodontic retainer constructed from composite
      and multistrand orthodontic wire provides an esthetic and efficient system for
      maintained retention. The development, indications for use, and clinical
      techniques are described. The range of materials reported for clinical use in
      construction of bonded orthodontic retainers are reviewed. Recommmendations based
      on the literature are made. This review implicates placement of insufficient
      resin or use of a resin with inadequate abrasion resistance in the failure of
      bonded fixed retainers.

PMID- 7625398
TI  - Point/counterpoint.

PMID- 7625399
TI  - Electronic mail on the Internet.

PMID- 7625400
TI  - Protecting your assets from lawsuits and claims.
AB  - Asset protection is an essential component of any prudent financial plan. In
      today's dangerous business climate, a lifetime of successful accomplishments can
      be obliterated by a single unexpected event. The objective of asset protection is
      to insure a level of certainty and security as one make his way through the
      hazards of everyday life.

PMID- 7625401
TI  - Heterogeneity in meta-analysis of data from epidemiologic studies: a commentary.

PMID- 7625402
TI  - Invited commentary: benefits of heterogeneity in meta-analysis of data from
      epidemiologic studies.

PMID- 7625403
TI  - Dietary intake of energy and animal foods and endometrial cancer incidence. The
      Iowa women's health study.
AB  - To assess the relations of dietary intake of energy and animal foods to
      endometrial cancer risk, dietary analyses were performed using data from a
      prospective cohort study of over 23,000 postmenopausal Iowa women who responded
      to a mailed questionnaire in 1986 and were followed through the end of 1992 for
      cancer incidence and total mortality. Usual intakes of 127 food items were
      measured by a semiquantitative food frequency questionnaire. After 7 years of
      follow-up, 216 incident endometrial cancer cases had been ascertained. There was
      no statistically significant association of dietary intake of energy and most
      animal foods with endometrial cancer incidence over the 7-year follow-up period.
      Stratified analyses, however, suggested that intake of energy from plant foods
      may be inversely associated with endometrial cancer risk in the latter years of
      follow-up (trend test, p = 0.03), while high intake of energy and foods from
      animal sources related to slightly, but not statistically significantly, elevated
      risks of this cancer in the earlier years of follow-up. The only significant dose
      response relation observed in food group analyses was for processed meat and
      fish, for which a significant 50% excess risk of endometrial cancer was found
      among women in the highest versus the lowest tertile of intake. This study
      suggests that dietary intake of energy and most animal foods is not related to or
      is only weakly related to the risk of endometrial cancer among postmenopausal US
      women.

PMID- 7625404
TI  - Respiratory illness, beta-agonists, and risk of idiopathic dilated
      cardiomyopathy. The Washington, DC, Dilated Cardiomyopathy Study.
AB  - An epidemiologic study was carried out to examine the possible role of beta
      agonists and other respiratory medications in the development of idiopathic
      dilated cardiomyopathy. Associations with respiratory medications, bronchial
      asthma, emphysema, and chronic bronchitis were examined by comparing newly
      diagnosed cases (n = 129) ascertained from five Washington, DC, area hospitals
      for the period 1990-1992 with neighborhood controls (n = 258) identified by using
      a random digit dialing technique. The cases and controls were matched on sex and
      5-year age intervals and were compared in the analysis using conditional logistic
      regression methods. A statistically significant association was observed between
      idiopathic dilated cardiomyopathy and history of emphysema or chronic bronchitis
      (adjusted odds ratio (OR) = 4.4, 95% confidence interval (CI) 1.6-12.4). The
      association with bronchial asthma was of borderline significance (adjusted OR =
      1.9, 95% CI 0.9-4.2). Associations were also observed with use of oral beta
      agonists (adjusted OR = 3.4, 95% CI 1.1-11.0) and beta-agonist inhalers or
      nebulization (adjusted OR = 3.2, 95% CI 1.4-7.1), as well as with use of oral
      corticosteroids, inhaled corticosteroids or cromolyn, and theophylline
      medications. A total of 20.0% (23 of 115) of the cases had a reported history of
      beta-agonist inhaler use compared with 6.7% (17 of 254) of the controls. The
      strength of these associations was diminished when the temporal relation between
      exposure to beta-agonist inhalers or oral preparations and clinical diagnosis of
      idiopathic dilated cardiomyopathy was taken into account, however, and the
      associations with duration of beta-agonist medication use were not statistically
      significant (p > 0.05). The results of this study suggest, but do not prove, that
      use of beta-agonists has an etiologic role in idiopathic dilated cardiomyopathy.

PMID- 7625405
TI  - Age-related macular degeneration is associated with atherosclerosis. The
      Rotterdam Study.
AB  - Age-related macular degeneration is the most frequent cause of blindness in the
      elderly. A vascular basis of the disease has been suggested, but not confirmed.
      The association between atherosclerosis and this type of macular degeneration was
      investigated in 104 subjects with and 1,324 subjects without macular degeneration
      as part of the population-based Rotterdam Study. The study was performed between
      March 1990 and July 1993 in a suburb of Rotterdam, the Netherlands. Macular
      degeneration was assessed on fundus photographs. Carotid atherosclerosis was
      ultrasonographically evaluated by measurement of the common carotid intima-media
      thickness and by assessment of the presence of atherosclerotic plaques.
      Atherosclerosis in arteries of the lower extremities was studied by determination
      of the ankle-arm systolic blood pressure ratio. In subjects younger than age 85
      years, plaques in the carotid bifurcation were associated with a 4.7 times
      increased prevalence odds of macular degeneration (95% confidence interval (CI)
      1.8-12.2); those with plaques in the common carotid artery showed an increased
      prevalence odds of 2.5 (95% CI 1.4-4.5). The intima-media thickness of the common
      carotid arteries was not significantly different. Lower extremity arterial
      disease (ankle-arm index less than 0.90 on at least one side) was associated with
      a 2.5 times increased prevalence odds (95% CI 1.4-4.5). These findings suggest
      that atherosclerosis may be involved in the etiology of age-related macular
      degeneration.

PMID- 7625406
TI  - Hispanic versus white smoking patterns by sex and level of education.
AB  - Although past studies have compared cigarette smoking patterns in Hispanics and
      whites, few have examined differences within sex and educational subgroups. Data
      are presented for 1,088 Hispanic women and men (89% Mexican-American origin) and
      pairwise matched white women and men (544 pairs), aged 25-74 years, who
      participated in population-based cross-sectional surveys in California in 1979
      1990. Each pair was matched on age, sex, educational level, city of residence,
      and survey time period. There were large differences in smoking prevalence rates
      between Hispanic and white pairs with low educational attainment. White women and
      men with less than a high school education were approximately twice as likely to
      be current daily cigarette smokers as were similarly educated Hispanic women and
      men (46.1 vs. 20.6% for women and 52.7 vs. 30.1% for men). As the level of
      education increased, these ethnic differences in smoking decreased and became
      negligible among those who completed college. Virtually all low-educated white
      men (92.5%) and most low-educated white women (73.1%) were either current or
      former daily smokers. There were large ethnic differences in rates of smoking
      cessation advice from a physician; only 8.3% of low-educated Hispanic men who
      were current daily smokers had ever been advised by a physician to stop smoking,
      compared with 59.6% of low-educated white men. These data confirm ethnic
      differences in smoking behavior and identify the high smoking rates of white men
      and women with low educational attainment, thus delineating an often unrecognized
      group toward whom tobacco prevention and cessation activities should be directed.

PMID- 7625407
TI  - Household and community determinants of exposure to involuntary smoking: a study
      of urinary cotinine in children and adolescents.
AB  - The study examines the role of several potential predictors of urinary cotinine
      levels in a cross-sectional sample of 1,072 nonsmoking children and adolescents
      in Latium, Italy, during 1990-1991. As expected, there was a strong relation
      between passive exposure to smoking and the amount of maternal and paternal self
      reported smoking. The urinary cotinine level increased with a decreasing level of
      paternal education and with an increasing index of household crowding; self
      report of recent exposure to smoking outside the home was a strong predictor of
      the biologic marker. The analysis was then restricted to 346 subjects whose
      parents claimed that they were nonsmokers and that there were no smokers at home.
      In this group, however, 57 children reported some active smoking at home by their
      parents. Those with parents suspected to be "deceivers" had higher level of
      urinary cotinine than did those truly not exposed. In addition, urinary cotinine
      in this group was clearly associated with duration of exposure to smoking outside
      home. The study indicates that both factors related to family circumstances and
      exposure outside the household setting are strong determinants of urinary
      cotinine levels. The finding may be considered a direct confirmation that passive
      smoking among children should be viewed as a specific community responsibility.

PMID- 7625408
TI  - Rates of transcervical and pertrochanteric hip fractures in the province of
      Quebec, Canada, 1981-1992.
AB  - Two distinct subtypes of hip fracture, transcervical and pertrochanteric, can be
      distinguished on the basis of the anatomical location of the injury. While the
      epidemiology of hip fractures has been well described, typically, little or no
      distinction is made between these subtypes. The objective of this study was to
      compare and contrast age- and sex-specific rates of transcervical and
      pertrochanteric fractures in Quebec, Canada. The data for this study were
      obtained from a database containing records of all persons discharged from all
      hospitals in Quebec from 1981 to 1992. Rates of hip fractures were calculated by
      using the population aged 50 years and older as the denominator, and changes in
      rates over time were assessed using Poisson regression. There were no
      statistically significant trends in the changes in rates over time (i.e., 95
      percent confidence intervals overlapped the null value). Among women below age 70
      years, transcervical fractures were more common, whereas among older women,
      pertrochanteric fractures predominated. Among men, pertrochanteric fractures
      predominated at all ages. There was a marked seasonal variation in the occurrence
      of all hip fractures combined: Compared with the summer months, the relative risk
      of all hip fractures during the winter was 1.32 (95 percent confidence interval
      1.28-1.36). The results of this study indicate that the two subtypes of hip
      fracture, transcervical and pertrochanteric, have different patterns of
      occurrence, suggesting different risk factor profiles. Clearly, a
      multidisciplinary research approach is needed before it will be possible to
      untangle the complex relation between the metabolic processes occurring at the
      level of the individual and the distribution of the disease in the population.

PMID- 7625409
TI  - Case-control study of the risk factors for eclampsia.
AB  - A case-control study was conducted to investigate risk factors for eclampsia. A
      total of 66 cases of eclampsia were ascertained from deliveries between 1977 and
      1992 at two hospitals in Houston, Texas, based on the criteria defined by the
      American College of Obstetrics and Gynecology. Cases were matched to
      nonpreeclamptic controls on a 4:1 ratio on the basis of hospital and month of
      delivery. The ratio of eclampsia cases to number of deliveries over the study
      period was 0.63 per 1,000. In a logistic regression model, risk factors for
      eclampsia included 1) two or fewer prenatal care visits (odds ratio (OR) = 6.10,
      95% confidence interval (CI) 2.26-16.41), 2) urinary tract infection (OR = 4.23,
      95% CI 1.27-14.06), 3) primigravidity (OR = 2.87, 95% CI 0.97-8.44), 4) obesity
      (OR = 2.49, 95% CI 0.78-7.96), 5) black ethnicity (OR = 2.25, 95% CI 0.88-5.78),
      6) history of diabetes (OR = 2.07, 95% CI 0.45-9.62), and 7) age < or = 20 years
      (OR = 1.55, 95% CI 0.47-5.10). Nulliparity was not shown to be a risk factor for
      eclampsia when controlled for primigravidity, and neither were previous history
      of abortion or previous history of pregnancy-induced hypertension. Thus, prior
      pregnancy itself, independent of outcome and preeclamptic/eclamptic
      complications, appears to be the protective factor against eclampsia in a
      subsequent pregnancy.

PMID- 7625410
TI  - Correcting standardized rate ratios for imprecise classification of a
      polychotomous exposure variable with limited data.
AB  - The analysis of exposure misclassification has received considerable attention in
      the epidemiologic literature, with the result that methods for correcting many
      summary risk estimates for such misclassification are well known. However, the
      application of such methods typically requires more data than are usually
      published (for example, the complete set of exposure- and age-specific mortality
      rates). The authors show, under the assumption that exposure misclassification
      occurs independently of disease status and confounder level, that it is possible
      to obtain estimates of standardized rate ratios corrected for a given pattern of
      misclassification from only the published standardized risk ratios and the
      misclassification matrix. This technique allows readers of scientific literature
      to perform post hoc sensitivity analysis of published risk estimates.

PMID- 7625411
TI  - Re: "Risk of premenopausal breast cancer and use of electric blankets".

PMID- 7625412
TI  - Re: "A population-based case-cohort evaluation of the efficacy of mammographic
      screening for breast cancer".

PMID- 7625413
TI  - Ambulatory education: expanding undergraduate experience in medical education. A
      CDIM commentary.

PMID- 7625414
TI  - Estrogen and coronary artery disease in postmenopausal women.

PMID- 7625415
TI  - Estrogen acutely increases peripheral blood flow in postmenopausal women.
AB  - PURPOSE: To test the acute effect of estrogen on peripheral blood flow and
      vascular resistance in postmenopausal women. PATIENTS AND METHODS: Eleven
      normotensive, post-menopausal female volunteers (mean age 53 +/- 6 years) were
      studied. Six women were in natural menopause and 5 had had a hysterectomy (mean
      age of the menopause 49 +/- 3 years). We used a double-blind, randomized protocol
      to assess the acute response to sublingual estradiol-17 beta (1 mg) on the
      forearm resistance vessels, compared with sublingual placebo. Blood flow was
      measured by strain-gauge plethysmography, and mean peripheral vascular resistance
      was then calculated. Mean blood pressure was also measured. RESULTS: The mean
      blood flow induced by estradiol-17 beta after 40 minutes was significantly
      greater than that induced by placebo (3.9 +/- 0.5 mL/100 mL per minute versus 2.4
      +/- 0.4 mL/100 mL per minute, respectively, P < 0.05). The forearm resistance was
      significantly reduced at 40 minutes after estradiol-17 beta compared with placebo
      (25.7 +/- 4.4 resistance units (RU) to 44.4 +/- 6.4 RU, respectively, P < 0.05).
      Mean blood pressure 40 minutes after the administration of estradiol-17 beta was
      no different when compared with placebo (91 +/- 1.5 mm Hg versus 90 +/- 2.5 mm
      Hg, respectively, P = NS). CONCLUSIONS: These results indicate that the acute
      administration of estradiol-17 beta affects blood flow in the peripheral
      vasculature in human subjects. The mechanism of this effect has not been
      determined, but it may explain some of the beneficial effects of estrogen on the
      vascular system and have future therapeutic potential in postmenopausal women.

PMID- 7625416
TI  - Prognosis after hospitalization for acute myocardial infarction not accompanied
      by typical ischemic chest pain. The Multicenter Diltiazem Postinfarction Trial
      Research Group.
AB  - PURPOSE: Although ischemic-type chest pain generally identifies acute myocardial
      infarction (AMI), some patients are hospitalized for AMI without this symptom.
      Long-term mortality and morbidity after AMI presenting with alternative warning
      symptoms have not been examined previously. We therefore assessed the prognostic
      implications of the absence of typical chest pain as well as other recognized
      risk predictors in patients hospitalized with AMI. PATIENTS AND METHODS: Data
      were obtained during the Multicenter Diltiazem Postinfarction Trial. Pain status
      and other baseline characteristics were determined prospectively by study
      coordinators according to simple, prespecified criteria. Patients were then
      examined every 3 to 4 months until trial completion. We applied chi-square
      methods, life-table analysis, and multivariate analysis to assess the strength
      and independence of prognostic power associated with each baseline variable.
      RESULTS: Of 2,464 patients enrolled 3 to 15 days after enzyme-documented AMI, 115
      patients lacked typical ischemic-type chest in on presentation (the "nonpainful"
      group). After 25 months' mean follow-up, cardiac mortality was 20% for nonpainful
      patients and 10% for 2,349 patients with typical pain (the "painful" group), P <
      0.001. Similar increments were seen in total deaths (27% nonpainful versus 13%
      painful, P < 0.001) and cardiac events, namely, cardiac death or nonfatal
      reinfarction (24% nonpainful versus 17% painful, P = 0.001). Late congestive
      heart failure was more frequent (17% nonpainful versus 7% painful, P < 0.001),
      but unstable angina was less (6% nonpainful versus 16% painful, P = 0.005). At
      outset, nonpainful patients had more left ventricular dysfunction and diabetes
      mellitus. However, nonpainful AMI predicted worse outcome even when these
      problems were absent. Logistic regression confirmed greater cardiac death risk in
      the nonpainful group (hazard ratio = 2.05) and showed that predictive power of
      nonpainful status was independent of baseline ejection fraction, Holter data,
      concomitant diabetes mellitus, and other covariates. CONCLUSIONS: Patients
      hospitalized with nonpainful AMI are much more likely to experience late cardiac
      death or congestive heart failure than are patients with painful AMI. In part,
      this probably reflects more ventricular damage with alternative warning symptoms
      such as dyspnea. However, our data suggest that defective perception of warning
      pain also provides a long-term risk to life that is independent of previously
      known predictors of poor outcome.

PMID- 7625417
TI  - A community-wide outbreak of hepatitis A: risk factors for infection among
      homosexual and bisexual men.
AB  - PURPOSE: To assess risk factors for hepatitis A infection among homosexual and
      bisexual men during a community-wide outbreak of hepatitis A in New York City.
      PATIENTS AND METHODS: Twenty-five homosexual and bisexual men, 20 to 49 years of
      age with hepatitis A identified from health department surveillance data (cases)
      were compared with 42 homosexual and bisexual men of similar age distribution who
      were seronegative for hepatitis A virus and identified from private physician
      offices (controls). Odds ratio (OR) were determined for acute hepatitis A
      infection according to demographics, numbers of sexual partners, frequency of
      specific sexual behaviors, and self-reported human immunodeficiency virus status.
      RESULTS: Cases had more anonymous sex partners (0 to 1 partner versus > 1
      partner) than controls during the 6 weeks before illness onset (OR = 4.4, 95%
      confidence interval [CI] 1.4 to 14.4). Cases were more likely than controls to
      have engaged in group sex (OR = 3.8, 95% CI 1.1 to 12.6). Among specific sexual
      behaviors examined, oral-anal intercourse (oral role) and digital-rectal
      intercourse (digital role) with anonymous sex partners were more commonly
      reported by cases than controls (OR = 9.7, 95% CI 1.2 to 78.7 and OR = 2.6, 95%
      CI 1.0 to 7.4, respectively). Multivariate analysis showed that > 1 anonymous sex
      partner, group sex, oral-anal intercourse, and digital-rectal intercourse were
      associated with illness in models controlling for duration of sexual activity.
      Because these variables were highly correlated, independent risk could not be
      evaluated in a single model. CONCLUSIONS: Hepatitis A infection among homosexual
      and bisexual men is associated with oral-anal and digital-rectal intercourse, as
      well as with increasing numbers of anonymous sex partners and group sex. These
      findings reinforce the importance of developing educational activities for
      homosexual and bisexual men that focus on risk reduction for hepatitis A as well
      as other sexually transmitted disease spread via the fecal-oral route.

PMID- 7625418
TI  - Serious falls in hospitalized patients: correlates and resource utilization.
AB  - PURPOSE: To evaluate the correlates of serious falls in hospitalized patients and
      the resource utilization associated with such falls. PATIENTS AND METHODS: This
      retrospective case-control study was performed in an urban tertiary care
      hospital. The 62 cases included all inpatients with available charts who were
      reported as having fallen with a resulting fracture (n = 22), dislocation (n =
      1), or laceration or hematoma (n = 39) after being admitted between January 1987
      and March 1991. The 62 controls were matched by date of hospitalization (within 3
      months), age (within 5 years), gender, and length of stay up to the time of the
      fall. RESULTS: Univariate correlates of falls (P < 0.05) included severity of
      underlying disease, Charlson comorbidity score, and Confusion Assessment Method
      (CAM) score. In multivariate conditional logistic regression analyses, only the
      Charlson index (P < 0.006) and the CAM score (P < 0.03) were independent
      correlates of a fall. Exposure to any of a number of drugs did not predict falls,
      but the power to detect drug effects was limited. A combination of the Charlson
      comorbidity and CAM scores identified a population at substantially increased
      risk of fall, including 50% (31/62) of fallers, versus 16% (10/62) of controls
      (odds ratio 5.2; 95% confidence interval, 2.4 to 12). In multivariate analyses,
      falls were also independently correlated with increases in length of stay (P <
      0.004) and total charges (P < 0.008). Fallers stayed 12 days longer and had
      charges $4,233 higher than controls, after adjustment for potential clinical and
      nonclinical confounders. CONCLUSION: Falls during hospitalization are commoner in
      confused patients and those with greater comorbidity. This profile differs from
      that of fallers in the community, probably because hospitalized patients are
      sicker. Injurious falls are associated with substantially increased resource
      utilization.

PMID- 7625420
TI  - Neuropsychiatric lupus erythematosus: a 10-year prospective study on the value of
      diagnostic tests.
AB  - PURPOSE: To evaluate which serologic, cerebrospinal fluid (CSF), and
      neuroradiographic tests alone or in combination are most useful in the diagnosis
      of neuropsychiatric lupus erythematosus (NPLE). PATIENTS AND METHODS: Prospective
      study of patients with systemic lupus erythematosus (SLE) hospitalized with
      neuropsychiatric disease between January 1982 and December 1991. Special tests
      evaluated as part of this study included serum antinuclear antibodies, complement
      levels, serum and CSF antineuronal antibodies, CSF special protein studies
      (immunoglobulin G [IgG] index and oligoclonal bands), serum antiribosomal-P
      antibodies, serum antiphospholipid antibodies, and cranial magnetic resonance
      imaging (MRI). Diagnostic sensitivity, specificity, and positive predictive value
      (PPV) were determined for single tests and combinations of tests. RESULTS: Fifty
      two NPLE patients were categorized by neuropsychiatric presentation (32 diffuse,
      10 focal, and 10 complex presentations) and compared to 14 SLE control patients.
      Each NPLE patient with a diffuse or complex presentation had abnormal CSF IgG
      index/oligoclonal bands, elevated CSF antineuronal antibodies, and/or serum
      antiribosomal-P antibodies, yielding a sensitivity of 100%, specificity of 86%,
      and PPV of 95% for this combination of tests. Nine of 10 patients with focal
      presentations and all with complex disease had evidence of vasculitis/livedo
      reticularis, antiphospholipid antibodies, and/or a cranial MRI with multiple
      lesions, giving a sensitivity of 95%, specificity of 86%, and a PPV of 90% for
      this battery of tests. These combinations of tests correctly diagnosed all nine
      SLE patients whose initial diagnosis proved to be incorrect based on subsequent
      clinical course. Abnormal test results frequently normalized or improved with
      successful therapy. CONCLUSIONS: Specific tests for CSF antibodies are most
      useful diagnostically in diffuse NPLE, implicating autoantibodies in the
      pathogenesis of this NPLE presentation. In those patients with diffuse NPLE who
      present with primarily psychiatric disease, serum antiribosomal-P antibodies
      appear to be helpful. In contrast, focal NPLE appears to be mostly secondary to
      vascular occlusion, and the presence of dermal vasculitis/livedo reticularis,
      antiphospholipid antibodies, and/or an abnormal cranial MRI are most helpful
      diagnostically. Patients with complex presentations demonstrate abnormalities
      characteristic of both diffuse and focal NPLE. Abnormal tests can be followed
      serially and appear to correlate with clinical responses to therapy.

PMID- 7625419
TI  - Alendronate treatment of the postmenopausal osteoporotic woman: effect of
      multiple dosages on bone mass and bone remodeling.
AB  - BACKGROUND: The effects of the aminobisphosphonate alendronate sodium on bone
      mass and markers of bone remodeling were investigated. PATIENTS AND METHODS: In a
      multicenter, randomized, double-blind, placebo-controlled, 2-year study, 188
      postmenopausal women, aged 42 to 75 years, with low bone mineral density (BMD) of
      the lumbar spine were randomly assigned to 1 of 6 daily treatment groups: placebo
      for 2 years, alendronate 5 or 10 mg for 2 years, alendronate 20 or 40 mg for 1
      year followed by placebo for 1 year, or alendronate 40 mg for 3 months followed
      by 2.5 mg for 21 months. All subjects were given 500 mg/d of elemental calcium as
      calcium carbonate. RESULTS: At each dose, alendronate produced significant
      reductions in markers of bone resorption and formation, and significantly
      increased bone mass at the lumbar spine, hip, and total body, as compared with
      decreases (significant at lumbar spine) in subjects receiving placebo. In the 10
      mg group, mean urinary deoxypyridinoline/creatinine had declined by 47% at 3
      months, and mean serum osteocalcin by 53% at 6 months. Mean changes in BMD over
      24 months with 10 mg alendronate were +7.21% +/- 0.49% for the lumbar spine,
      +5.27% +/- 0.70% for total hip, and +2.53% +/- 0.68% for total body (each P <
      0.01) compared to changes of -1.35% +/- 0.61%, -1.20% +/- 0.64% and -0.31% +/-
      0.44% at these sites, respectively, with placebo treatment. Progressive increases
      in BMD of both lumbar spine and total hip were observed in the second year of
      treatment with 10 mg alendronate (both P < 0.05). CONCLUSION: Alendronate, a
      potent inhibitor of bone resorption, reduces markers of bone remodeling and
      significantly increases BMD at the lumbar spine, hip, and total body, and is well
      tolerated at therapeutic doses (5 or 10 mg daily) in the treatment of
      osteoporosis in postmenopausal women.

PMID- 7625421
TI  - Diagnosis and therapeutic monitoring of invasive candidiasis by rapid enzymatic
      detection of serum D-arabinitol.
AB  - BACKGROUND: Using a rapid automated enzymatic assay, we prospectively
      investigated serum D-arabinitol (DA), a biochemical marker of invasive
      candidiasis, in a large population of high-risk patients to determine its
      potential diagnostic, therapeutic, and prognostic significance in invasive
      candidiasis. PATIENTS AND METHODS: A total of 3,223 serum samples were collected
      from 274 patients with cancer. Serum DA concentrations were determined in coded
      serum samples analyzed by rapid enzymatic assay. Creatinine also was analyzed in
      the same system to determine a serum DA and creatinine ratio (DA/Cr). The
      sensitivity, specificity, correlation with therapeutic response, and prognostic
      significance were analyzed for all patient study groups. RESULTS: A DA/Cr of > or
      = 4.0 mumol/L per mg/dL was detected in 31 (74%) of all 42 cases of fungemia and
      25 (83%) of the 30 cases of the subset of persistent fungemia. Elevated DA/Cr was
      detected in 4 (40%) of 10 patients with tissue-proven, deeply invasive
      candidiasis and negative blood cultures (eg, hepatosplenic candidiasis or
      localized abscess) and 7 (44%) of 16 cases of deep mucosal candidiasis (eg,
      esophageal candidiasis). Elevated serial DA/Cr levels also were detected in
      persistently febrile and granulocytopenic patients requiring empirical
      amphotericin B. Among 26 assessable cases of fungemia, abnormally elevated DA/Cr
      values were detected in 14 (54%) before, 10 (38%) after, and 2 (8%)
      simultaneously with the first microbiologic report of fungemia. The trends of
      serial DA/Cr values correlated with therapeutic response in 29 (85%) of 34
      patients with assessable cases of fungemia, decreasing in 8 (89%) of 9 patients
      with clearance of fungemia and increasing in 21 (84%) of 25 patients with
      persistence of fungemia. Among the 34 assessable patients with fungemia,
      mortality was directly related to the trend of serial DA/Cr determinations over
      time: 71% among fungemic patients who had persistently elevated or increasing
      DA/Cr, and 18% among the fungemic patients who had resolving DA/Cr or never had
      elevated DA/Cr (P < 0.01). CONCLUSIONS: Rapid enzymatic detection of DA in
      serially collected serum samples from high-risk cancer patients permitted
      detection of invasive candidiasis, early recognition of fungemia, and therapeutic
      monitoring in DA-positive cases. Serially collected serum DA determinations
      complement blood cultures for improving detection and monitoring therapeutic
      response in patients at risk for invasive candidiasis.

PMID- 7625422
TI  - Pattern of recovery of the hypothalamic-pituitary-thyroid axis following
      radioactive iodine therapy in patients with Graves' disease.
AB  - PURPOSE: To characterize the time course of recovery of the hypothalamic
      pituitary-thyroid (HPT) axis by determining the frequency, onset, duration, and
      clinical attributes of the central hypothyroid phase following 131I therapy for
      Graves' disease and to examine whether the central hypothyroid phase is due to
      direct pituitary thyrotroph suppression or to hypothalamic thyrotropin-releasing
      hormone (TRH) deficiency. PATIENTS AND METHODS: Twenty-one hyperthyroid patients
      with Graves' disease evaluated at a university endocrine clinic and treated with
      radioactive iodine were prospectively studied. Serial thyroid function levels
      (serum thyroxine [T4], free thyroxine [free T4], triiodothyronine [T3], and
      thyroid-stimulating hormone [TSH]) were measured and TRH stimulation tests were
      performed at 2 to 4 week intervals for all subjects following 131I treatment.
      None of the patients was treated with thionamides after receiving 131I therapy.
      RESULTS: Nineteen (90%) of the patients with Graves' disease experienced a
      transient central hypothyroid phase defined as the presence of a suppressed or
      inappropriately normal TSH level despite a low free T4 level following 131I
      treatment. This phase occurred a mean of 62.8 +/- 5.1 days following 131I
      treatment, persisted for an average of 24.7 +/- 2.4 days, and was not predictive
      of eventual treatment outcome. All patients had concordantly low T4 and T3 levels
      during this period and exhibited a blunted TSH response to TRH compared to 29
      euthyroid control subjects, suggesting primary feedback suppression at the level
      of the pituitary thyrotrophs. The suppressed thyrotrophs required a minimum of 2
      weeks to recover once patients became hypothyroid. The length of preexisting
      hyperthyroidism, basal free T4 elevation, and administered dose of 131I failed to
      predict the duration of the central hypothyroid phase, although a higher dose of
      131I was associated with an earlier onset of central hypothyroidism (r = -.51, P
      < 0.05). CONCLUSIONS: Clinicians should be aware of the delay in the recovery of
      the HPT axis that occurs in the majority of patients with Graves' disease treated
      with 131I and is manifested by a transient central hypothyroid phase. The blunted
      TSH response to TRH stimulation during this period suggests that suppression
      occurs primarily at the level of the pituitary thyrotrophs. The use of sensitive
      TSH measurements alone to monitor these patients during this period is not
      helpful and may be misleading.

PMID- 7625423
TI  - The decision to enter a randomized trial of tamoxifen for the prevention of
      breast cancer in healthy women: an analysis of the tradeoffs.
AB  - OBJECTIVE: Interest in breast cancer prevention has led to the Breast Cancer
      Prevention Trial (BCPT), a controversial randomized trial of tamoxifen for women
      at risk for breast cancer. The goal of our study was to determine whether the
      potential benefits of enrolling in the randomized trial of prophylactic tamoxifen
      outweigh the potential risks. METHODS: We used a decision analytic model based on
      the available data on tamoxifen treatment benefits in women with breast cancer
      and extrapolated to its use in healthy women. RESULTS: For a 50-year-old woman
      with a breast cancer risk twice that of the average woman her age, the BCPT
      offers an increase in life expectancy of about 9 days, a gain that is modest
      compared with other health interventions. For women ages 35 to 60 who meet the
      minimum risk of breast cancer for trial eligibility, the trial increases life
      expectancy by about 8 or 9 days. Assumptions about the effect of tamoxifen on the
      incidence of endometrial and liver cancer and on quality of life associated with
      tamoxifen did not alter our findings. CONCLUSIONS: Advocates and opponents of the
      BCPT should temper their concerns to reflect the modest absolute benefits and
      harms associated with the trial. Although women at increased risk for breast
      cancer should be aware of the likely overall benefit associated with entry into
      the trial, for most women, entry into the BCPT is unlikely to alter substantially
      their length of life, in either a beneficial or harmful manner.

PMID- 7625424
TI  - Elevator talk: observational study of inappropriate comments in a public space.
AB  - OBJECTIVES: We conducted a study to determine the type and frequency of
      inappropriate comments made by hospital employees while riding hospital
      elevators. METHODS: Four observers rode in elevators at five hospitals, listening
      for any comments made by hospital employees that might be deemed inappropriate.
      All potentially inappropriate comments were reviewed by the research team and
      were classified as inappropriate if they met at least one of the following
      criteria: violated patient confidentiality, raised concerns about the speaker's
      ability or desire to provide high-quality patient care, raised concerns about
      poor quality of care in the hospital (by persons other than the speaker), or
      contained derogatory remarks about patients or their families. RESULTS: We
      observed 259 one-way elevator trips offering opportunity for conversation. We
      overheard a total of 39 inappropriate comments, which took place on 36 rides
      (13.9% of the trips). The most frequent comments (18) were violations of patients
      confidentiality. Next most frequent (10 comments) were unprofessional remarks in
      which clinicians talked about themselves in ways that raised questions about
      their ability or desire to provide high-quality patient care. Other comments
      included derogatory statements about the general quality of hospital care (8) and
      derogatory remarks about patients (5). Physicians were involved in 15 of the
      comments, nurses in 10, and other hospital employees in the remainder.
      CONCLUSION: Inappropriate comments took place with disturbing frequency in the
      elevator rides we sampled. These comments did not exclusively involve violations
      of patient confidentiality, but encompassed a range of discussions that health
      care employees must be careful to avoid.

PMID- 7625425
TI  - Contemporary management of acute myocardial infarction.
AB  - Acute myocardial infarction, the leading cause of death in western society, has
      been the focus of more randomized clinical trial effort over the past decade than
      any other area of medicine. As a result of this worldwide effort, involving
      hundreds of thousands of patients with myocardial infarction, data have
      accumulated showing substantially lower mortality of acute myocardial infarction
      with simple interventions such as i.v. thrombolytic therapy, aspirin, beta
      blockers, and angiotensin-converting enzyme inhibitors. Emergency coronary
      angioplasty appears to be a suitable alternative to i.v. thrombolytic therapy in
      skilled centers. Several previously recommended therapies (routine i.v.
      lidocaine, calcium channel blockers, magnesium, nitrates) have not been proved to
      be life-saving. Whether routine coronary arteriography should be employed after
      myocardial infarction remains controversial, but it is generally accepted that
      patients with evidence of residual ischemia after infarction, either spontaneous
      or provoked by stress testing, should undergo prophylactic coronary
      revascularization.

PMID- 7625426
TI  - Mucocutaneous paraneoplastic manifestations of hematologic malignancies.
AB  - PURPOSE: To review the clinical manifestations, pathophysiology, and oncologic
      implications of the major mucocutaneous paraneoplastic syndromes that can appear
      in patients with hematologic malignancies. METHODS: A comprehensive search of the
      medical literature was conducted. RESULTS: In vesiculobullous conditions,
      although the primary lesions are blisters, observed abnormalities may include
      large, flaccid bullae (pemphigus vulgaris), superficial crusted erosions
      (pemphigus foliaceus), or erythema multiforme-like lesions (paraneoplastic
      pemphigus). Paraneoplastic neutrophilic dermatoses include Sweet's syndrome and
      pyoderma gangrenosum. In both of these conditions, the skin lesions are
      characterized by a dermal infiltrate of mature neutrophils. Vascular dermatoses
      include vasculitis and erythromelagia. Papulosquamous conditions are
      characterized by small (papules) or large (plaques) raised skin lesions and are
      usually associated with solid tumors. Amyloidosis is a malignancy-related
      condition that probably stems from immune dysregulation. RECOMMENDATIONS:
      Continued surveillance of patients with potential cutaneous paraneoplastic
      syndromes is necessary, since the malignancy may not be immediately detectable.
      Some of the cutaneous paraneoplastic syndromes will respond to specific measures,
      such as systemic corticosteroid therapy, but for the most part, successful
      resolution requires eradication of the underlying malignancy.

PMID- 7625427
TI  - Mrs. Lincoln.

PMID- 7625428
TI  - Toxoplasmic encephalitis with normal CT scan and pathologic MRI.

PMID- 7625429
TI  - Lupus anticoagulant and heparin-associated bleeding.

PMID- 7625430
TI  - Diabetes mellitus: a disease of abnormal cellular calcium metabolism?

PMID- 7625431
TI  - Fatal acute hepatic necrosis due to fluconazole.

PMID- 7625432
TI  - Kabuki make-up (Niikawa-Kuroki) syndrome in the Byelorussian register of
      congenital malformations: ten new observations.
AB  - We describe clinical manifestations and historical data on ten patients with
      Kabuki make-up syndrome. All patients are of European ancestry and all have the
      characteristics of the syndrome, including typical face, retarded physical
      development, and mild to moderate mental retardation. Two of the probands have
      low-normal intelligence. Prominent and broad philtrum was described as an
      important component manifestation of the syndrome. In three families some
      clinical manifestations of Kabuki make-up syndrome were observed in parents and
      some other relatives of the probands in three generations. Some phenotypic
      differences between Asian and non-Asian patients were noted. The possible cause
      of the syndrome is discussed. The present observations and a literature review
      suggest autosomal dominant inheritance with different expressivity of the Kabuki
      make-up syndrome.

PMID- 7625434
TI  - Family with partial monosomy 10p and trisomy 10p.
AB  - We report on a family with an abnormality of 10p. The propositus has monosomy for
      the distal region of 10p and severe psychomotor delay, growth failure, congenital
      heart defect, multicystic kidney, grade V vesicoureteric reflux, and neurosensory
      hearing loss. The mother and the elder brother of the propositus carry a balanced
      reciprocal translocation (5q;10p)(q35.3;p12.3). A retarded and epileptic maternal
      aunt was found to have dup(10p). Study of the family history led to the
      successful obstetric management of a subsequent twin pregnancy in which an
      affected fetus with dup(10p) was identified and selectively terminated, while the
      other normal twin was delivered at term without problems.

PMID- 7625433
TI  - Bilateral ulna hypoplasia, club feet, and mental retardation: a new mesomelic
      syndrome.
AB  - We report on 2 sibs with a previously unreported type of mesomelia of the upper
      limbs due to ulnar hypoplasia. Prenatal diagnosis was made by ultrasound during
      one pregnancy and an affected fetus was confirmed. This family documents a
      previously unreported autosomal recessive syndrome.

PMID- 7625435
TI  - X microchromosome with additional chromosome anomalies found in Ullrich-Turner
      syndrome.
AB  - Using standard cytogenetic methods coupled with molecular techniques, the
      following karyotype mos 45,X/46,XXq+/46,X+mar (X)/47,XXq+,+mar(X), was identified
      in a patient with Ullrich-Turner syndrome (UTS). High-resolution banding (n =
      650) of the metaphase chromosomes yielded a breakpoint at q28 on the Xq+
      rearranged chromosome. FISH was used to determine the presence of Y-containing
      DNA in the Xq+ and the mar(X) chromosomes. The following molecular probes were
      used: DYZ1, DYZ3, and spectrum orange WCP Y. The lack of specific hybridization
      of these probes was interpreted as a low risk of gonadoblastoma in this patient.
      Using X-chromosome- and centromere-specific probes, FISH demonstrated the
      presence of hybridizing material on both rearranged chromosomes, the Xq+ and
      mar(X). Finally, we determined that the mar(X) and Xq+ chromosomes contained
      telomeres in the absence of any interstitial telomeric hybridizing material. A
      micro-X chromosome is present in this UTS patient. Delineation of events leading
      toward the mechanisms responsible for the multiple DNA rearrangements required to
      generate the micro-X and Xq+ chromosomes awaits future studies.

PMID- 7625436
TI  - Agenesis of the corpus callosum and Dandy-Walker malformation associated with
      hemimegalencephaly in the sebaceous nevus syndrome.
AB  - The sebaceous nevus syndrome is sometimes associated with hemimegalencephaly and
      a group of related abnormalities including ipsilateral gyral malformation, mental
      retardation, seizures, especially infantile spasms, and facial hemihypertrophy.
      This combination has been described as the "neurological variant of epidermal
      nevus syndrome." Other brain malformations have been reported only rarely. We
      report on a child with a subtle sebaceous nevus associated with
      hemimegalencephaly who also had agenesis of the corpus callosum and Dandy-Walker
      malformation.

PMID- 7625437
TI  - Acrofacial dysostosis of unknown type: nosology of the acrofacial dysostoses.
AB  - We describe a stillborn girl with an unclassified form of mandibulofacial
      dysostosis, a postaxial defect of the right, and a preaxial defect of the left
      hand. The Nager syndrome is characterized by preaxial limb defects, whereas the
      Genee-Wiedemann syndrome (= Miller syndrome) by postaxial limb defects. We
      briefly review the established acrofacial dysostoses (AFD) and discuss the
      position of our case in the current classification.

PMID- 7625439
TI  - New autosomal recessive form of amelia.
AB  - Amelia is a rare, usually sporadic malformation. We report on a family in which
      three fetuses had amelia of the upper limbs and variable deficiency of the lower
      limbs. The fetuses also had minor facial anomalies. Recurrence of the condition
      in sibs of both sexes suggests autosomal recessive inheritance. Recurrent amelia
      has been documented in only a few families most often associated with a different
      set of malformations. Possibly, mutations in more than one gene with different
      modes of transmission can lead to this severe limb deficiency. We speculate that
      the mutation found in our cases interferes with formation of the apical
      ectodermal ridge in the upper limbs and results in its premature degeneration in
      the lower limbs.

PMID- 7625438
TI  - Choledochal cyst associated with rare hand malformation.
AB  - We report on an 8-year-old boy with choledochal cyst associated with most unusual
      hand malformation. Review of the literature and possible etiopathogenesis are
      discussed.

PMID- 7625440
TI  - Severe case of Al Awadi/Raas-Rothschild syndrome or new, possibly autosomal
      recessive facio-skeleto-genital syndrome.
AB  - A Sicilian girl whose parents were first cousins had a severe tetramelic limb
      deficiency (amelia of lower limbs, peromelia of upper limbs) and other defects
      including cleft lip and palate, facial anomalies, athelia, low umbilicus, bladder
      exstrophy, no external genitalia, and anteriorly displaced anus. This probably
      represents a particularly severe case of Al Awadi/Raas-Rothschild syndrome
      (limb/pelvis-hypoplasia/aplasia syndrome, LPHAS), but the possibility of a new
      autosomal recessive facio-skeleto-genital syndrome cannot be excluded.

PMID- 7625441
TI  - Renal tubular acidosis in the Silver-Russell syndrome.
AB  - Several patients with the Silver-Russell syndrome (SRS) attending our Genetics
      Clinic were diagnosed as having persistent metabolic acidosis. Since this
      abnormality has not been reported previously in the SRS, we reexamined 33 SRS
      patients to evaluate the frequency and type of metabolic acidosis, the clinical
      and laboratory findings, and the growth pattern in SRS patients with and without
      metabolic acidosis. Among them, 14 had a consistent decrease in HCO3- levels.
      Renal studies in acidotic patients showed urine pH of 5.8 and 24 h urine calcium
      of < 2.4 mg/kg/24 h; serum creatinine, excretion of glucose, and amino acids were
      normal, as were renal ultrasound and excretory urography findings. These data
      supported the diagnosis of renal tubular acidosis, probably type II; the patients
      were treated with oral bicarbonate and acidosis was corrected successfully.
      Clinical manifestations were similar in acidotic and non-acidotic patients. The
      nutritional indices at diagnosis and at last evaluation (at least 8 months after
      diagnosis) were abnormally low in all patients; however, acidotic patients,
      treated with bicarbonate, showed an improvement of nutritional status
      particularly in the weight/height index, although the difference between groups
      after follow-up did not reach statistical significance. We suggest that metabolic
      acidosis due to renal tubular acidosis, probably type II, may occur in children
      with the SRS and should be looked for and treated in all patients.

PMID- 7625442
TI  - Clinical profile of Angelman syndrome at different ages.
AB  - We describe 47 patients with Angelman syndrome (AS) from Belgium and the
      Netherlands, including the anamnestic data, the clinical and the behavioral
      attributes at different ages. The clinical picture of AS is most distinct between
      the ages of 2-16 years. Most patients of this age group show at least 8 of the
      major characteristics (bursts of laughter, happy disposition, hyperactive
      behaviour, microcephaly, brachycephaly, macrostomia, tongue protrusion,
      mandibular prognathism, widely spaced teeth, stiff and puppetlike movements,
      typical stature, wide based gait) beside the mental retardation and (almost)
      absence of speech, which is a universal trait. The diagnosis in infants is based
      on only a limited number of clinical characteristics or on anamnestic data.
      However, if these occur in combination, they are indicative of AS. In older
      patients, the diagnosis may be hampered in part because of the changing
      behavioral characteristics and the decreasing frequency of fits. Other
      manifestations, such as scoliosis, may become more pronounced with age.

PMID- 7625443
TI  - Developmental trends of sleep-disordered breathing in Prader-Willi syndrome: the
      role of obesity.
AB  - Polysomnographic recordings of 43 children and adults with Prader-Willi syndrome
      (PWS) were inspected and classified into 5 age groups. The effect of age and body
      mass index (BMI) on measures of breathing, oxygen saturation, and sleep
      efficiency were analyzed. Body mass index (BMI) increased significantly between
      early childhood and preadolescent groups. Subjecting the data to analysis of
      variance showed an overall significant effect of BMI but no age effect on
      breathing parameters and oxygen saturation. Increased BMI was associated with
      decreased oxygen saturation and with higher apnea/hypopnea index. Sleep
      efficiency index was significantly lower in adults than in young children,
      preadolescent, and adolescent groups. These findings emphasize the role of
      obesity in the development of sleep-related breathing abnormalities and nocturnal
      oxygen desaturation in patients with PWS.

PMID- 7625444
TI  - Submicroscopic deletions at 22q11.2: variability of the clinical picture and
      delineation of a commonly deleted region.
AB  - DiGeorge anomaly (DGA) and velo-cardiofacial syndrome (VCFS) are frequently
      associated with monosomy of chromosome region 22q11. Most patients have a
      submicroscopic deletion, recently estimated to be at least 1-2 Mb. It is not
      clear whether individuals who present with only some of the features of these
      conditions have the deletion, and if so, whether the size of the deletion varies
      from those with more classic phenotypes. We have used fluorescence in situ
      hybridization (FISH) to assess the deletion status of 85 individuals referred to
      us for molecular analysis, with a wide range of DGA-like or VCFS-like clinical
      features. The test probe used was the cosmid sc11.1, which detects two loci about
      2 Mb apart in 22q11.2. Twenty-four patients carried the deletion. Of the deleted
      patients, most had classic DGA or VCFS phenotypes, but 6 deleted patients had
      mild phenotypes, including 2 with minor facial anomalies and velopharyngeal
      incompetence as the only presenting signs. Despite the great phenotypic
      variability among the deleted patients, none had a deletion smaller than the 2-Mb
      region defined by sc11.1. Smaller deletions were not detected in patients with
      particularly suggestive phenotypes who were not deleted for sc11.1, even when
      tested with two other probes from the DGA/VCFS region.

PMID- 7625446
TI  - Chromosome instability in ICF syndrome: formation of micronuclei from
      multibranched chromosomes 1 demonstrated by fluorescence in situ hybridization.
AB  - We report on a new patient with immunodeficiency, centromeric heterochromatin
      instability, and facial anomalies (the ICF syndrome). Studies with traditional
      cytogenetic methods demonstrate that aberrations in this syndrome primarily
      involve the centromeric regions of chromosomes 1 and 16. We applied fluorescence
      in situ hybridization (FISH) using "painting" probes for chromosomes 1 and 16 to
      document the progression of centromeric instability from simple decondensation
      aberrations to the subsequent formation of complex multibranched chromosomes 1,
      and finally to the interphase aberrations of nuclear projections and micronuclei
      involving both chromosomes 1 and 16. The loss of the large multibranched
      chromosome 1 configurations from the cells as micronuclei suggests that the
      centromeric aberrations subsequently interfere with normal chromosome movement at
      anaphase in ICF syndrome. Circular areas of counterstained chromatin were
      observed by FISH in the micronuclei corresponding to the intertwined segments of
      centromeric heterochromatin seen involving multibranched chromosomes 1 in the
      patient's G-banded chromosome study. The current hypothesis of recessive
      inheritance for this disorder suggests that the chromosomal aberrations are not a
      causative event in this syndrome; however, the chromosome aberrations are clearly
      an important basic diagnostic criterion.

PMID- 7625447
TI  - Non-random X chromosome inactivation in an affected twin in a monozygotic twin
      pair discordant for Wiedemann-Beckwith syndrome.
AB  - Wiedemann-Beckwith syndrome (WBS) is a syndrome including exomphalos,
      macroglossia, and generalized overgrowth. The locus has been assigned to 11p15.5,
      and genomic imprinting may play a part in the expression of one or more genes
      involved. Most cases are sporadic. An excess of female monozygotic twins
      discordant for WBS have been reported, and it has been proposed that this excess
      could be related to the process of X chromosome inactivation. We have therefore
      studied X chromosome inactivation in 13-year-old monozygotic twin girls who were
      discordant for WBS. In addition, both twins had Tourette syndrome. The twins were
      monochorionic and therefore the result of a late twinning process. This has also
      been the case in previously reported discordant twin pairs with information on
      placentation. X chromosome inactivation was determined in DNA from peripheral
      blood cells by PCR analysis at the androgen receptor locus. The affected twin had
      a completely skewed X inactivation, where the paternal allele was on the active X
      chromosome in all cells. The unaffected twin had a moderately skewed X
      inactivation in the same direction, whereas the mother had a random pattern.
      Further studies are necessary to establish a possible association between the
      expression of WBS and X chromosome inactivation.

PMID- 7625448
TI  - "C" trigonocephaly syndrome: report of a child with agenesis of the corpus
      callosum and tetralogy of Fallot, and review.
AB  - We report on a new case of the Opitz "C" trigonocephaly syndrome. Our patient had
      agenesis of the corpus callosum, an anomaly seen only twice previously, and
      tetralogy of Fallot, described only once before. A review shows that a
      combination of conotruncal heart defects and midline brain anomalies
      characterizes patients with this entity.

PMID- 7625445
TI  - Screening for mtDNA diabetes mutations in Pima Indians with NIDDM.
AB  - More than half of the Pima Indians over age 35 years have non-insulin-dependent
      (type II) diabetes mellitus (NIDDM). Extensive data indicate the importance of
      maternal diabetes in determining their risk for diabetes. Generally, the risk of
      having NIDDM is higher in patients with affected mothers than affected fathers.
      This has been attributed to intrauterine factors, but recently mitochondrial
      inheritance has been raised as an alternative hypothesis. In other populations,
      several families and individuals with diabetes due to a mitochondrial DNA point
      mutation at nucleotide 3243 in the tRNA(leu(UUR)) gene have been described, as
      has one family with a 10.4 kb mitochondrial DNA duplication/deletion. We tested
      whether these specific mitochondrial gene mutations could explain a portion of
      the excess maternal transmission seen in the Pima Indians. Mitochondrial DNA
      obtained from blood lymphocytes of 148 Pima Indians with NIDDM was screened both
      for the point mutation at nt 3243, and the 10.4 kb duplication/deletion. Neither
      of these mutations was detected, and although a small proportion of the excess
      maternal transmission in Pima Indians could still be due to yet undescribed
      mitochondrial mutations or imprinted nuclear genes, our data support the role of
      the intrauterine environment in this population.

PMID- 7625449
TI  - Identification of supernumerary ring chromosome 1 mosaicism using fluorescence in
      situ hybridization.
AB  - We report on a 15-year-old black boy with severe mental retardation, multiple
      congenital anomalies, and a supernumerary ring chromosome mosaicism. Fluorescence
      in situ hybridization with a chromosome 1 painting probe (pBS1) identified the
      ring as derived from chromosome 1. The karyotype was 46,XY/47,XY,+r(1)(p13q23). A
      review showed 8 reports of ring chromosome 1. In 5 cases, the patients had a non
      supernumerary ring chromosome 1 resulting in partial monosomies of the short
      and/or long arm of chromosome 1. In 3 cases, the presence of a supernumerary ring
      resulted in partial trisomy of different segments of chromosome 1. In one of
      these cases the supernumerary ring was composed primarily of the centromere and
      the heterochromatic region of chromosome 1, resulting in normal phenotype. Our
      patient represents the third report of a supernumerary ring chromosome 1
      resulting in abnormal phenotype.

PMID- 7625450
TI  - FISH analysis in Prader-Willi and Angelman syndrome patients.
AB  - We report on a combined high resolution cytogenetic and fluorescent in situ
      hybridization study (FISH) on 15 Prader-Willi syndrome (PWS) and 14 Angelman
      syndrome (AS) patients. High resolution banding showed a microdeletion in the
      15q11-q13 region in 7 out of 15 PWS patients, and FISH analysis of the D15S11 and
      SNRPN cosmids demonstrated absence of the critical region in three additional
      cases. Likewise 8 out of 14 AS patients were found to be deleted with FISH, using
      the GABRB3 specific cosmid, whereas only 4 of them had a cytogenetically
      detectable deletion.

PMID- 7625451
TI  - Craniofacial and dental characteristics of Silver-Russell syndrome.
AB  - We found significant differences in a craniometric, cephalometric, and dental
      study of 19 Silver-Russell syndrome patients (13 without growth hormone
      treatment) with appropriate controls. Although head circumference was normal for
      age, head length was increased, while cranial and facial widths and facial
      heights were reduced. Posterior facial height, posterior cranial base length,
      cranial base height, and mandibular body size were significantly smaller than in
      healthy children of the same height. Articulatory speech disorders were common.
      Enamel defects pointed to an early prenatal insult. Delayed dental age and small
      mandibular and cranial base dimensions support the possibility of physiological
      growth hormone deficiency in many Silver-Russell syndrome children; however,
      facial soft tissue structures were strikingly different from those observed in
      classical growth hormone deficiency.

PMID- 7625452
TI  - Angelman syndrome: consensus for diagnostic criteria. Angelman Syndrome
      Foundation.

PMID- 7625453
TI  - New manifestations in an infant with Neu Laxova syndrome.

PMID- 7625454
TI  - Noonan syndrome associated with thromboembolic brain infarcts and posterior
      circulation abnormalities.

PMID- 7625455
TI  - Clients, consumers, providers, and products: where will it all end?

PMID- 7625456
TI  - Alzheimer's dementia.

PMID- 7625457
TI  - Research on field-based services: models for reform in the delivery of mental
      health care to populations with complex clinical problems.
AB  - OBJECTIVE: Clinical services for psychiatrically impaired populations have only
      recently been studied with scientifically valid designs to explore innovations in
      structure, accessibility, and financing. Health systems reform in the United
      States has provided the impetus for better defining clinically effective and cost
      sensitive models for mental health services. This article reviews assertive
      community treatment, used for adults with severe mental illnesses, and
      multisystemic therapy, used for adolescents with serious emotional disturbances,
      as examples of service system innovations that have been studied with controlled
      clinical trial designs and have demonstrated efficacy in treating difficult and
      costly clinical populations. METHOD: The authors reviewed the published
      controlled clinical trials of assertive community treatment and multisystemic
      therapy, focusing on the clinical and administrative elements that distinguish
      them from traditional service systems. RESULTS: A qualitative assessment of these
      two approaches suggests that they share common elements, with important
      implications for mental health policy. Specifically, the use of an ecological
      model of behavior applied to mental health patients is critical to both systems.
      In addition, therapeutic principles emphasizing pragmatic (outcome-oriented)
      treatment approaches, home-based interventions, and individualized goals are key
      elements of their success. Most important, both systems embody a therapeutic
      philosophy demanding therapist accountability, in which personnel are rewarded
      for clinical outcomes and therapeutic innovation rather than for following a
      prescribed plan. CONCLUSIONS: As empirically tested approaches, assertive
      community treatment and multisystemic therapy provide a scientific foundation for
      continued reform and serve to illustrate critical elements in designing new
      community treatment initiatives for behavioral as well as medical conditions.

PMID- 7625458
TI  - Characteristics and significance of untreated major depressive disorder.
AB  - OBJECTIVE: This study sought to describe the characteristics and consequences of
      untreated major depressive disorder. METHOD: As part of a family study of
      probands with major affective disorders, raters assessed 3,119 first-degree
      relatives, spouses, and comparison subjects. When 2,237 (71.7%) of these
      individuals were reassessed 6 years later, 547 had experienced episodes of major
      depressive disorder in the interval. Those who had sought any form of treatment
      for any episode of major depressive disorder in the interval were compared, by
      baseline demographic characteristics and clinical features of their worst
      episodes of major depressive disorder, to those who had not. Individuals who had
      had untreated major depressive disorder were then compared, by changes in
      socioeconomic status and by levels of psychosocial impairment at follow-up, to a
      matched group with no major depressive disorder in the interval. RESULTS: The
      worst episodes of 313 treated individuals, compared to those of 234 untreated
      individuals, were characterized by older age, symptoms of the endogenous subtype,
      longer durations, and the presence of disruption in role function. Each of these
      factors contributed independently to the distinction between treated and
      untreated episodes. Untreated individuals experienced significant psychosocial
      impairment on follow-up but did not show the economic disadvantages shown
      elsewhere for probands who began follow-up as they sought treatment at tertiary
      medical centers. CONCLUSIONS: These data suggest that illness characteristics and
      age determine the decision to seek treatment for major depressive disorder.
      Untreated depression is apparently associated with long-standing psychosocial
      difficulties but not with serious economic consequences.

PMID- 7625459
TI  - Antidepressant-induced mania and cycle acceleration: a controversy revisited.
AB  - OBJECTIVE: The longitudinal course of 51 patients with treatment-refractory
      bipolar disorder was examined to assess possible effects of heterocyclic
      antidepressants on occurrence of manic episodes and cycle acceleration. METHOD:
      Using criteria established from life charts, investigators rated the patients'
      episodes of mania or cycle acceleration as likely or unlikely to have been
      induced by antidepressant therapy. Discriminant function analyses were performed
      to assess predictors of vulnerability to antidepressant-induced mania or cycle
      acceleration. Further, the likelihood of future antidepressant-induced episodes
      in persons who had had one such episode was assessed. RESULTS: Thirty-five
      percent of the patients had a manic episode rated as likely to have been
      antidepressant-induced. No variable was a predictor of vulnerability to
      antidepressant-induced mania. Cycle acceleration was likely to be associated with
      antidepressant treatment in 26% of the patients assessed. Younger age at first
      treatment was a predictor of vulnerability to antidepressant-induced cycle
      acceleration. Forty-six percent of patients with antidepressant-induced mania,
      but only 14% of those without, also showed antidepressant-induced cycle
      acceleration at some point in their illness. CONCLUSIONS: Mania is likely to be
      antidepressant-induced and not attributable to the expected course of illness in
      one-third of treatment-refractory bipolar patients, and rapid cycling is induced
      in one-fourth. Antidepressant-induced mania may be a marker for increased
      vulnerability to antidepressant-induced cycle acceleration. Antidepressant
      induced cycle acceleration (but not antidepressant-induced mania) is associated
      with younger age at first treatment and may be more likely to occur in women and
      in bipolar II patients.

PMID- 7625460
TI  - T2 hyperintensities in bipolar disorder: magnetic resonance imaging comparison
      and literature meta-analysis.
AB  - OBJECTIVE: Accumulating evidence suggests a greater number of T2 abnormalities in
      the brains of patients with bipolar I disorder. The authors sought to evaluate
      the presence of signal "hyperintensities" in both bipolar I and II subjects and
      systematically review the existing literature. METHOD: Magnetic resonance images
      of the brain were obtained prospectively for 29 patients with bipolar I disorder,
      26 patients with bipolar II disorder, and 20 normal comparison subjects. The
      presence and location of signal hyperintensities in three brain regions
      (periventricular white matter, subcortical gray matter, and deep white matter)
      were evaluated. RESULTS: No significant differences were found between groups for
      the presence of subcortical gray or deep white matter hyperintensities.
      Periventricular hyperintensities were more common in bipolar I patients (62%)
      than in bipolar II patients (38%) and normal comparison subjects (30%). Within
      patient groups, medication use was not significantly different for those with or
      without the presence of white matter hyperintensities. The literature on bipolar
      disorder and signal hyperintensities is reviewed. A meta-analysis of the pooled
      data in the literature on bipolar illness and signal hyperintensities revealed
      that the odds of having a T2 hyperintensity are significantly greater for bipolar
      I than for normal comparison subjects. CONCLUSIONS: Having bipolar I disorder
      significantly increases the chance of having white matter changes in the brain.
      This study suggests that bipolar II patients may be more similar than bipolar I
      patients to comparison subjects on T2 measures. The possible pathophysiological
      significance of hyperintensities is discussed.

PMID- 7625461
TI  - An MRI study of brain size in autism.
AB  - OBJECTIVE: This study was undertaken to obtain detailed measurements of the
      volume of the brain, using magnetic resonance imaging (MRI), in a carefully
      selected group of autistic subjects and comparison subjects. METHOD: Twenty-two
      male autistic subjects and 20 male volunteer comparison subjects were examined
      with detailed (1.5-mm slices) MRI throughout the entire brain. Total brain, total
      brain tissue, and total lateral ventricle volumes were measured by using manual
      tracing and automated techniques. RESULTS: After height and performance IQ were
      controlled, autistic subjects had significantly greater total brain, total
      tissue, and total lateral ventricle volumes than comparison subjects.
      CONCLUSIONS: These findings suggest that male autistic subjects have enlarged
      brains and that enlargement is a result of both greater brain tissue volume and
      greater lateral ventricle volume.

PMID- 7625462
TI  - Trauma-related symptoms in veterans of Operation Desert Storm: a 2-year follow
      up.
AB  - OBJECTIVE: This study was a 2-year follow-up in an ongoing prospective
      examination of development of trauma-related symptoms over time in a community
      group of veterans of Operation Desert Storm. METHOD: Sixty-two National Guard
      reservists, from one medical and one military police unit, completed the
      Mississippi Scale for Combat-Related Posttraumatic Stress Disorder and a DSM-III
      R-based posttraumatic stress disorder (PTSD) symptom scale 1 month, 6 months, and
      2 years after returning from the Middle East. Differences in symptom severity
      over time were analyzed by using repeated measure analyses of variance. RESULTS:
      Scores on the Mississippi scale, but not the DSM-III-R PTSD scale, increased
      significantly over time. Symptoms of hyperarousal were more severe at all time
      points than were symptoms of reexperiencing or avoidance. Level of combat
      exposure, as reflected by the Desert Storm trauma questionnaire, was
      significantly associated with the score on the Mississippi scale at 2 years but
      not at 1 month or 6 months. All subjects who met the Mississippi scale's
      diagnostic criteria for PTSD at 1 or 6 months still met the criteria at 2 years.
      CONCLUSIONS: Although symptoms were relatively mild, there was an overall
      increase in PTSD symptoms over 2 years. The statistical relationship between
      level of combat exposure and PTSD symptoms at 2 years, and not before, suggests
      that it may take time for the consequences of traumatic exposure to become
      apparent. Moreover, degree of exposure may be important in predicting the
      eventual development of symptoms. Continued follow-up will address the evolution
      of PTSD symptoms in Gulf War veterans.

PMID- 7625463
TI  - Predictors of alprazolam discontinuation with and without cognitive behavior
      therapy in panic disorder.
AB  - OBJECTIVE: In a previous paper the authors reported survival data for 20 panic
      disorder patients whose therapeutic doses of alprazolam were tapered by one of
      two methods: slow, flexible drug taper with supportive medical management or the
      same taper procedure carried out concurrently with cognitive behavior therapy.
      This report is an analysis of predictors of drug discontinuation success in that
      study. In addition, between-group comparisons of clinical measures at follow-up
      are presented. METHOD: The subjects in the previous study (10 in each group) were
      assessed blindly at baseline, 2 weeks after completion of drug taper, and at 3-
      and 6-month follow-up. Potential predictors of drug discontinuation success were
      tested by using logistic regression. Between-group differences in symptom
      severity at 3-month follow-up were examined by using analyses of covariance.
      RESULTS: Thirteen subjects (nine receiving alprazolam plus cognitive behavior
      therapy and four receiving alprazolam only) completed the drug taper on schedule
      and were still medication free at follow-up. A single variable--baseline-to
      posttaper change in anxiety sensitivity--predicted drug status at follow-up in
      85% of the cases. At follow-up, subjects in the combined-treatment group were
      significantly more improved on measures of anxiety, depression, catastrophic
      thinking related to anxiety, perception of emotional control, and disability than
      subjects in the drug-only group. CONCLUSIONS: Across groups, reduction in the
      fear of anxiety symptoms was the best predictor of patients' ability to achieve
      and maintain drug abstinence. Some implications of that finding for the
      pharmacotherapy of panic disorder are discussed.

PMID- 7625464
TI  - Clinical aspects of chronic use of alprazolam and lorazepam.
AB  - OBJECTIVE: The authors' goal was to determine the clinical characteristics of
      persistent users of alprazolam or lorazepam who wished to discontinue their
      medication. METHOD: Long-term users (daily use for more than 3 months) of
      alprazolam (N = 34) or lorazepam (N = 97) who entered an outpatient treatment
      program for discontinuation of benzodiazepines were carefully assessed. Detailed
      histories of benzodiazepine use were obtained; a structured interview was used to
      make psychiatric diagnoses based on DSM-III-R criteria. RESULTS: The majority of
      patients were using low therapeutic doses of medication (lorazepam: mean = 2.7
      mg/day; alprazolam: mean = 1.2 mg/day) and had either maintained their initial
      daily dose over time or decreased it. Individuals tended to shift their use of
      medication from an as-prescribed to an as-needed pattern. Forty-seven percent of
      the patients were diagnosed with at least one current anxiety disorder, most
      commonly generalized anxiety. At least one diagnosable personality disorder was
      found in 45% of the patients, most commonly obsessive-compulsive personality
      disorder. Patterns of benzodiazepine use were influenced by age, gender, and past
      history of alcohol dependence. CONCLUSIONS: Long-term users of
      alprazolam/lorazepam seeking treatment for discontinuation had clinically
      important past and current psychiatric histories. They used a constant or
      decreasing dose of medication and made attempts to stop their use. Persistent use
      of alprazolam/lorazepam for therapeutic purposes did not represent abuse or
      addiction as the terms are usually understood. A substantial proportion of these
      patients may be receiving appropriate maintenance therapy for a chronic
      psychiatric condition.

PMID- 7625465
TI  - Irregular breathing during sleep in patients with panic disorder.
AB  - OBJECTIVE: The authors examined the nocturnal breathing patterns of patients with
      panic disorder to determine whether these individuals had respiratory
      irregularities at a time when anxiety was not manifest. METHOD: Respiratory
      polysomnography was conducted on 14 medication-free patients with panic disorder
      and 14 healthy comparison subjects. Semiautomated indices of ventilatory
      variability were calculated for representative 3-minute, artifact-free sleep
      samples, and manually scored indices of irregular breathing were rated (blind to
      diagnosis) for the entire last 2 nights of sleep. RESULTS: Patients with panic
      disorder had evidence of abnormal sleep breathing as indicated by increased
      irregularity in tidal volume during REM and an increased rate of microapneas
      (i.e., brief [5-10-second] pauses in breathing). A subgroup of patients
      (including some with recent sleep panic attacks) had indices of subtle disorders
      in breathing during sleep that were above the 95th percentile for the comparison
      subjects. CONCLUSIONS: These findings extend the observations in the awake state
      that patients with panic disorder breathe more irregularly than healthy
      comparison subjects. The irregularities may be attributable to altered brainstem
      sensitivity to CO2 or to other as yet unexplained factors. A possible
      relationship between irregular nocturnal breathing and sleep panic attacks is
      discussed.

PMID- 7625466
TI  - Clinical correlates of early-onset and late-onset poststroke generalized anxiety.
AB  - OBJECTIVE: The authors' goal was to determine if generalized anxiety diagnosed
      while a patient was hospitalized for stroke (early onset) had the same clinical
      correlates as anxiety beginning 3 months or more after the stroke (late onset).
      METHOD: Patients with acute stroke (N = 142) were examined while they were in the
      hospital and 3, 6, 12, and 24 months later for the presence of anxiety symptoms.
      Patients underwent a structured psychiatric interview as well as assessment of
      cognitive, physical, and social function at each visit. Patients with early-onset
      and late-onset poststroke generalized anxiety were identified and compared to
      patients without poststroke generalized anxiety. RESULTS: The frequency of early
      onset poststroke generalized anxiety was 27% and that of late-onset poststroke
      generalized anxiety was 23%. Three-quarters of the anxious patients had comorbid
      major or minor depression. Patients who developed early-onset or late-onset
      poststroke generalized anxiety were no more socially, cognitively, or physically
      impaired than patients who did not develop anxiety. Early-onset but not late
      onset anxiety was associated with a previous history of psychiatric disorder. The
      median duration of late-onset anxiety was 3.0 months, and that of early-onset
      anxiety was 1.5 months. The presence of anxiety was significantly associated with
      depression; onset of depression and onset of anxiety occurred at approximately
      the same time. CONCLUSIONS: These findings suggest that although early-onset and
      late-onset poststroke generalized anxiety are phenomenologically similar, they
      may be the result of different pathophysiological mechanisms.

PMID- 7625467
TI  - Functional neuroanatomy of CCK4-induced anxiety in normal healthy volunteers.
AB  - OBJECTIVE: The authors tested the prediction of temporal cortex activation during
      experimentally induced anxiety by using positron emission tomography and the
      [15O]H2O bolus-subtraction method to determine regional cerebral blood flow (CBF)
      changes in normal volunteers challenged with a bolus injection of cholecystokinin
      tetrapeptide (CCK4). METHOD: Eight right-handed healthy subjects (five male,
      three female; mean age, 26.4 years) underwent four 60-second [15O]H2O scans
      separated by 15-minute intervals; each scan followed an intravenous bolus
      injection of either saline (placebo) or CCK4 (50 micrograms). Each subject
      received CCK4 once, as the first or second bolus, in a random-order, placebo
      controlled, double-blind fashion. Two of the three placebo conditions were
      nominally identical, and the remaining placebo was used to control for
      anticipatory anxiety. Magnetic resonance imaging scans were obtained for
      subsequent anatomical correlation of blood flow changes. RESULTS: CCK4, but not
      placebo, elicited a marked anxiogenic response, reflected by robust increases in
      subjective anxiety ratings and heart rate. CCK4-induced anxiety was associated
      with 1) robust and bilateral increases in extracerebral blood flow in the
      vicinity of the superficial temporal artery territory and 2) CBF increases in the
      anterior cingulate gyrus, the claustrum-insular-amygdala region, and the
      cerebellar vermis. CONCLUSIONS: Some of the temporopolar cortex CBF activation
      peaks previously reported in humans in association with drug- and non-drug
      induced anxiety, as well as the increase in regional CBF in the claustrum-insular
      amygdala region, may be of vascular and/or muscular origin.

PMID- 7625468
TI  - Desire for death in the terminally ill.
AB  - OBJECTIVE: Euthanasia and physician-assisted suicide have become prominent
      medical and social issues. This study investigated the prevalence of the desire
      for death in terminally ill patients, the stability of this desire over time, and
      its association with psychiatric disorders. METHOD: Two hundred terminally ill
      inpatients were given semistructured interviews that assessed their desire for
      death and evaluated them for major and minor depressive episodes according to the
      Research Diagnostic Criteria. Each patient also completed a short form of the
      Beck Depression Inventory and provided ratings of pain and social support. When
      possible, patients who expressed a desire for death received a follow-up
      interview after a 2-week interval. RESULTS: Although occasional wishes that death
      would come soon were common (reported by 44.5% of the patients), only 17 (8.5%)
      of these individuals acknowledged a serious and pervasive desire to die. The
      desire for death was correlated with ratings of pain and low family support but
      most significantly with measures of depression. The prevalence of diagnosed
      depressive syndromes was 58.8% among patients with a desire to die and 7.7% among
      patients without such a desire. Follow-up interviews were conducted with six
      patients; in four cases, the desire to die had decreased during the 2-week
      interval. CONCLUSIONS: The desire for death in terminally ill patients is closely
      associated with clinical depression--a potentially treatable condition--and can
      also decrease over time. Informed debate about euthanasia should recognize the
      importance of psychiatric considerations, as well as the inherent transience of
      many patients' expressed desire to die.

PMID- 7625469
TI  - A long-term, double-blind, placebo-controlled crossover trial of the efficacy of
      fluoxetine for trichotillomania.
AB  - OBJECTIVE: The authors' objective was to determine the efficacy of fluoxetine at
      high doses for the treatment of trichotillomania in a long-term, double-blind,
      placebo-controlled crossover trial. METHOD: Twenty-three adult chronic hair
      pullers agreed to take part in the trial, taking fluoxetine doses of up to 80
      mg/day. The 31-week trial consisted of a 2-week washout phase, a first treatment
      phase of 12 weeks, a 5-week washout phase, and a crossover second treatment phase
      of 12 weeks. Sixteen patients (14 women and two men) completed the trial.
      RESULTS: There were no significant differences between fluoxetine and placebo
      treatments for the measures of weekly severity of hair pulling, weekly severity
      of urge to pull, daily hair counts (or estimated hair pulled), or days of hair
      pulling. CONCLUSIONS: The efficacy of fluoxetine in the treatment of
      trichotillomania was not demonstrated in this study.

PMID- 7625470
TI  - The phototherapy light visor: more to it than meets the eye.
AB  - OBJECTIVE: The purpose of the study was to ascertain whether phototherapy light
      visors provide an effective treatment for seasonal affective disorder. Previous
      studies have demonstrated a moderate response rate but have failed to find any
      difference in efficacy between light intensities. METHOD: Subjects were randomly
      assigned to receive, over a 2-week treatment period, 30 minutes of morning
      phototherapy with a light visor that emitted either a dim (30-lux) red light or a
      bright (600-lux) white light. Raters were blind to treatment, and patients were
      unaware of the alternatives. Response was assessed by using the structured 21
      item Hamilton Depression Rating Scale, with an eight-item addendum for atypical
      depressive symptoms. Fifty-seven patients were enrolled across two sites.
      RESULTS: Patients assigned to the different visors had similar baseline
      depression scores and similar expectations of outcome. Hamilton depression scale
      scores declined by 34.6% for subjects given bright white light and by 40.9% for
      subjects given dim red light. Scores for atypical depressive symptoms fell by
      44.1% for patients assigned the bright white light visors and by 49.0% for
      patients assigned the dim red light visors. Altogether, 39.3% of the patients who
      received red light and 41.4% of the patients who received bright white light
      showed a full clinical response. CONCLUSIONS: There were no significant
      differences in therapeutic response between patients who were treated with red or
      white light. The results of this study suggest that the phototherapy light visor
      may function as an elaborate placebo. Alternative explanations, however, are
      considered.

PMID- 7625471
TI  - Images in psychiatry. Wilhelm Griesinger, M.D., 1817-1868.

PMID- 7625473
TI  - Body dysmorphic disorder in the DSM-IV field trial for obsessive-compulsive
      disorder.
AB  - OBJECTIVE: This study investigated the prevalence and phenomenology of body
      dysmorphic disorder in patients with obsessive-compulsive disorder. METHOD: The
      authors studied 442 patients who participated in the DSM-IV field trial for
      obsessive-compulsive disorder. RESULTS: Twelve percent (N = 51) of the patients
      had a lifetime comorbid diagnosis of body dysmorphic disorder. Patients with and
      without body dysmorphic disorder did not differ in demographic characteristics of
      obsessive-compulsive symptoms. Patients with obsessive-compulsive disorder and
      body dysmorphic disorder had more anxious, impulsive, and schizotypal features
      than patients with obsessive-compulsive disorder alone. Age at onset was similar
      for the two disorders, and severity correlated. However, insight was
      significantly more impaired for body dysmorphic disorder than for obsessive
      compulsive disorder. CONCLUSIONS: As previously thought, these findings suggest
      that the two disorders are strongly related but also have differences that
      require further investigation.

PMID- 7625472
TI  - Abnormalities of cAMP-dependent endogenous phosphorylation in platelets from
      patients with bipolar disorder.
AB  - OBJECTIVE: The aim of the study was to assess cAMP-dependent endogenous
      phosphorylation in platelets from euthymic bipolar patients. METHOD: Platelets
      from 10 drug-free euthymic patients with bipolar disorder were compared with
      those from 10 age- and sex-matched healthy subjects. Basal and cAMP-stimulated
      protein phosphorylation was examined in each group. RESULTS: Endogenous
      phosphorylation in both the healthy volunteers and the bipolar patients was
      significantly stimulated by cAMP; the major polypeptides had apparent molecular
      weights of 38 and 22 kDa. The cAMP-stimulated 32P incorporation differed between
      the bipolar patients and the comparison subjects only in the 22-kDa band.
      CONCLUSIONS: These data suggest a possible role of cAMP-dependent protein
      phosphorylation in the pathophysiology of bipolar disorder.

PMID- 7625474
TI  - Further evidence of a dose-response threshold for haloperidol in psychosis.
AB  - OBJECTIVE: The authors' goal was to determine whether higher doses of haloperidol
      improve antipsychotic response. METHOD: During a 2-week, double-blind, randomized
      fixed-dose study, 24 psychotic patients were given 4, 10, or 40 mg/day of
      haloperidol. RESULTS: No clinically relevant difference between groups in favor
      of the higher antipsychotic doses could be detected. CONCLUSIONS: Doses of 4
      mg/day of haloperidol appear to be as effective as higher doses in the treatment
      of psychosis.

PMID- 7625475
TI  - Dose-finding trial of D-cycloserine added to neuroleptics for negative symptoms
      in schizophrenia.
AB  - OBJECTIVE: The authors conducted a dose-finding study of D-cycloserine, a partial
      agonist at the glycine site of the N-methyl-D-aspartate subtype of the glutamate
      receptor, added to conventional neuroleptics for schizophrenic patients with
      prominent negative symptoms. METHOD: Nine patients with schizophrenia completed
      consecutive 2-week trials of placebo and four doses of D-cycloserine. Clinical
      assessments were videotaped and were scored by a rater who was blind to temporal
      sequence. RESULTS: D-Cycloserine at a dose of 50 mg/day produced a significant
      reduction (mean = 21%, SD = 28%) in negative symptoms and significantly improved
      reaction time as measured by Sternberg's Item Recognition Paradigm, a test
      mediated in part by prefrontal cortex. CONCLUSIONS: This preliminary evidence
      suggests that D-cycloserine may improve negative symptoms and cognitive deficits
      over a narrow dose range when added to conventional antipsychotic agents.

PMID- 7625476
TI  - Mental disorders and homicidal behavior in female subjects.
AB  - OBJECTIVE: Although violent behavior is one of the most important factors that
      have a detrimental effect on quality of life, there are very few quantitative
      epidemiological studies published on this issue. In particular, female homicidal
      behavior has remained poorly studied. This study reveals the association between
      some specific DSM-III-R disorders and female homicidal behavior. METHOD: The
      author reviewed forensic psychiatric examination of 127 female homicide offenders
      in Finland over a 13-year period. RESULTS: Female homicide offenders had about a
      10-fold higher odds ratio than the general female population for having
      schizophrenia or a personality disorder. The disorders with the most
      substantially higher odds ratios were alcohol abuse/dependence and antisocial
      personality disorder. CONCLUSIONS: Mental disorders appear to have a statistical
      relationship with homicidal behavior in countries with relatively low crime
      rates. On the basis of the data, there may be special subgroups of women among
      whom the risk of homicidal behavior is very high.

PMID- 7625478
TI  - Axis II diagnoses among volunteers for HIV testing and counseling.
AB  - OBJECTIVE: The authors' goal was to investigate the rate of personality disorders
      (axis II diagnoses in DSM-III-R) among adults at risk for AIDS. METHOD: The
      Personality Disorder Examination was administered to 260 volunteers for HIV
      testing and counseling. RESULTS: Thirty-seven percent of the subjects who
      subsequently tested seropositive for HIV and 20% of those who tested seronegative
      were given DSM-III-R axis II diagnoses on the Personality Disorder Examination.
      Thirty percent of the HIV-positive subjects who knew their serostatus before they
      were tested were given DSM-III-R axis II diagnoses. CONCLUSIONS: The meaningful
      rates of axis II diagnoses that preexisted determination of HIV status and the
      relation of these diagnoses to subsequently determined serostatus underscore the
      importance of adequately assessing the occurrence of personality disorder in
      individuals at risk for HIV infection.

PMID- 7625479
TI  - Prevalence of seasonal difficulties in mood and behavior among Japanese civil
      servants.
AB  - OBJECTIVE: Most prevalence studies of seasonal changes in mood and behavior have
      come from Western countries. The authors' goal was to determine the prevalence of
      seasonal changes in mood and behavior in a randomly selected group of Japanese
      workers. METHOD: They administered a Japanese translation of the Seasonal Pattern
      Assessment Questionnaire to 1,276 civil servants in Nagoya, Japan. RESULTS: The
      estimated prevalence of winter seasonal affective disorder was 0.86%, the
      estimated prevalence of winter subsyndromal seasonal affective disorder was
      0.86%, the estimated prevalence of summer seasonal affective disorder was 0.94%,
      and the estimated prevalence of summer subsyndromal seasonal affective disorder
      was 2.12%. CONCLUSIONS: The authors conclude that seasonal changes in mood and
      behavior occur in Japan, but at a lower frequency and with a different profile
      than in the United States or Europe.

PMID- 7625477
TI  - Alcohol and aldehyde dehydrogenase polymorphisms and the risk for alcoholism.
AB  - OBJECTIVE: The authors studied a large number of Japanese alcoholic patients and
      comparison subjects to establish the genotype frequencies of alcohol
      dehydrogenase-2 (ADH2) and mitochondrial aldehyde dehydrogenase (ALDH2) and to
      quantify the relative risk for alcoholism from the results. METHOD: The subjects
      were 655 alcoholic patients and 461 comparison subjects. ADH2 and ALDH2 were
      genotyped by the combination of polymerase chain reaction and hybridization
      methods. RESULTS: Active ALDH2 and usual ADH2 were significantly more frequent in
      the alcoholic patients. Inactive ALDH2 was not always associated with a low risk
      of alcoholism, and active ALDH2 was not always associated with high risk. In
      individuals with heterozygous inactive ALDH2 and usual ADH2, the odds ratio for
      alcoholism was high. CONCLUSIONS: The risk for alcoholism in Japanese has been
      accurately estimated on the basis of the genotype frequencies of ADH2 and ALDH2.
      Many Japanese may be protected from alcoholism by inactive ALDH2 and by higher
      frequencies of atypical ADH2.

PMID- 7625480
TI  - Fluoxetine withdrawal?

PMID- 7625481
TI  - Physical symptoms associated with paroxetine withdrawal.

PMID- 7625482
TI  - Cats as possible obsessive-compulsive disorder and medication models.

PMID- 7625483
TI  - Valproic acid-associated encephalopathy with coma.

PMID- 7625484
TI  - Trigeminal neuralgic syndrome after bright light therapy.

PMID- 7625485
TI  - The curriculum vitae and expert witness testimony.

PMID- 7625486
TI  - Adverse events in PTSD patients taking fluoxetine.

PMID- 7625487
TI  - Mental illness and youth suicide.

PMID- 7625488
TI  - Expressed emotion and depression in Egypt.

PMID- 7625489
TI  - Why more dysthymic patients may not have improved.

PMID- 7625490
TI  - Melancholia and response to ECT.

PMID- 7625491
TI  - Development of syllogistic reasoning.

PMID- 7625492
TI  - Vitamin A supplementation and morbidity in children born to HIV-infected women.

PMID- 7625493
TI  - The federal budget and women's health.

PMID- 7625494
TI  - The evolving epidemiology of syphilis.

PMID- 7625495
TI  - Community health workers: integral members of the health care work force.
AB  - As the US health care system strives to function efficiently, encourage
      preventive and primary care, improve quality, and overcome nonfinancial barriers
      to care, the potential exists for community health workers to further these
      goals. Community health workers can increase access to care and facilitate
      appropriate use of health resources by providing outreach and cultural linkages
      between communities and delivery systems; reduce costs by providing health
      education, screening, detection, and basic emergency care; and improve quality by
      contributing to patient-provider communication, continuity of care, and consumer
      protection. Information sharing, program support, program evaluation, and
      continuing education are needed to expand the use of community health workers and
      better integrate them into the health care delivery system.

PMID- 7625496
TI  - Redefining the goals of national drug policy: recommendations from a working
      group.
AB  - This paper discusses what the goals of national drug policy have been and
      suggests an alternative set of goals. The past emphasis on use reduction is found
      wanting. Total harm related to drugs can be viewed as the product of use and harm
      per use. Thus, reducing use usually serves to reduce harm. However, in some
      cases, use reduction programs may increase harm per use so much that they
      increase overall harm even as they succeed in reducing use. Hence, use reduction
      goals can be usefully augmented with the explicit objective of reducing the total
      harm created by the production, distribution, consumption, and control of drugs.
      Numerous programmatic recommendations flow from this approach.

PMID- 7625497
TI  - Adolescents' perceptions of their peers' health norms.
AB  - OBJECTIVES: The purpose of this study was to determine the relative importance
      adolescents place on preventive health behaviors. METHODS: Data were from a
      survey of California adolescents (n = 5040). Respondents were asked how important
      it was to their peers to avoid drugs, marijuana, cigarettes, heavy drinking, and
      drinking and driving and to maintain seat belt use, fitness, weight control, and
      healthy eating habits. Results were compared with data from a similar national
      survey (n = 6126). RESULTS: California teenagers perceived that their peers gave
      top priority to weight control: 85% of California teenagers believed that weight
      control was of high concern to girls in their age group. Avoiding drugs, not
      drinking and driving, and maintaining fitness ranked in the top five behaviors.
      The lowest ranked health behaviors were seat belt use, heavy drinking, and, last,
      eating healthily. In the national survey, healthy eating also ranked last.
      Although not identical in rank, teenage priorities for other health behaviors
      were consistent with the California results. CONCLUSION: Efforts are needed to
      bring adolescent health norms more into line with the objective risks of their
      health choices during this critical period of socialization.

PMID- 7625498
TI  - Company characteristics and workplace medical testing.
AB  - OBJECTIVES: This study measures the relative impact of company economic
      characteristics and workplace hazards on the prevalence of several types of
      medical testing. It uses the results to assess likely public health impacts of
      testing. METHODS: We used data on potential exposure to workplace hazards,
      medical testing, unionization, firm size, and turnover from the National
      Occupational Hazards Survey and the National Occupational Exposure Survey. Other
      sources provided industry-specific data on wages and turnover. Logistic
      regression analysis estimated the relationship of economic variables and
      workplace health risks to the prevalence of medical testing. RESULTS: Economic
      variables were related to the prevalence of testing. However, consistent positive
      relationships were not found between health hazards and testing. CONCLUSIONS:
      Employers' testing decisions may not be beneficial to the health of workers and
      may shift the costs of illness to workers or other employers. Safer firms may
      provide too much medical testing, and firms that are less safe may provide too
      little.

PMID- 7625499
TI  - The effects of vitamin A supplementation on the morbidity of children born to HIV
      infected women.
AB  - OBJECTIVE: The effects of vitamin A supplementation on morbidity of children born
      to human immunodeficiency virus (HIV)-infected women were evaluated in a
      population where vitamin A deficiency is not endemic. METHODS: A randomized,
      placebo-controlled trial of vitamin A supplementation was carried out in 118
      offspring of HIV-infected women in Durban, South Africa. Those assigned to
      receive a supplement were given 50,000 IU of vitamin A at 1 and 3 months of age;
      100,000 IU at 6 and 9 months; and 200,000 IU at 12 and 15 months. Morbidity in
      the past month was then recalled at each follow-up visit. Analysis was based on
      806 child-months. RESULTS: Among all children, the supplemented group had lower
      overall morbidity than the placebo group (OR = 0.69; 95% confidence interval [CI]
      = 0.48, 0.99). Among the 85 children of known HIV status (28 infected, 57
      uninfected), morbidity associated with diarrhea was significantly reduced in the
      supplemented infected children (OR = 0.51; 95% CI = 0.27, 0.99), whereas no
      effect of supplementation on diarrheal morbidity was noted among the uninfected
      children. CONCLUSION: In a population not generally vitamin A deficient, vitamin
      A supplementation for children of HIV-infected women appeared to be beneficial,
      reducing morbidity. The benefit was observed particularly for diarrhea among HIV
      infected children.

PMID- 7625500
TI  - The association between alcohol and breast cancer: popular press coverage of
      research.
AB  - OBJECTIVES: This study was undertaken to examine popular press reports of the
      association between alcohol and breast cancer. METHODS: Articles from scientific
      journals and stories from newspapers and magazines published from January 1,
      1985, to July 1, 1992, were retrieved from six on-line databases. Lay press
      stories were analyzed to determine which medical articles were publicized and
      what information was reported. RESULTS: Fifty-eight scientific articles on the
      relationship of alcohol and breast cancer were found, and 64 newspaper and 23
      magazine stories were retrieved. The press cited 11 studies, 19% of those
      published during the study period. Three studies were featured in 77% of popular
      press stories. No scientific review articles were reported. Behavioral
      recommendations were given to the public in 63% of stories. CONCLUSIONS: The vast
      majority of scientific studies on alcohol and breast cancer were ignored in press
      reports. We encourage researchers and the popular press to give the public a
      broader understanding of public health issues.

PMID- 7625501
TI  - The relationship between physicians' qualifications and experience and the
      adequacy of prenatal care and low birthweight.
AB  - OBJECTIVES: The purpose of this study was to examine the relationship between
      physicians' qualifications and experience and rates of completion of the
      recommended number of prenatal visits and delivery of a low-birthweight infant.
      METHODS: All deliveries performed by a permanently licensed physician in
      Massachusetts in 1990 (n = 80,537) were examined. Qualification was measured by
      board certification. Experience was measured by both volume of deliveries and
      duration of practice. RESULTS: Women cared for by a non-board-certified physician
      were less likely to receive the recommended number of prenatal visits (odds ratio
      [OR] = 0.67, 95% confidence interval [CI] = 0.54, 0.85) and were more likely to
      have a low-birthweight infant (OR = 1.20, 95% CI = 1.00, 1.42). Physicians with a
      smaller volume of deliveries or a shorter duration of practice were more likely
      to deliver a low-birthweight infant. CONCLUSIONS: The data show an association of
      board certification with rates of the recommended number of prenatal visits and
      low birthweight. In addition, volume and duration of practice were significantly
      associated with low birthweight. Further research should examine whether these
      associations are related to differences in patient referral or to physicians'
      judgement and efficiency in provision of prenatal care.

PMID- 7625502
TI  - Violence by male partners against women during the childbearing year: a
      contextual analysis.
AB  - OBJECTIVES: Many contextual analyses that bridge the micro-level-macro-level gap
      in identifying risk factors for adverse outcomes have not used methods
      appropriate for multilevel data. The purpose of this paper is to illustrate the
      application of appropriate multi-level analytic methods and discuss their
      implications for public health. METHODS: A previously published individual-level
      model of physical violence perpetrated by male partners during the childbearing
      year was reanalyzed to include variables describing the neighborhoods where the
      women resided. Logistic regression with estimation methods of the generalized
      estimating equation was used for the contextual analysis. To assess the
      advantages of the generalized estimating equation over conventional logistic
      regression, both were used for the two-level model. RESULTS: The regression
      coefficients from the contextual model differed from the betas obtained in the
      individual-level model. Not only were neighborhood-level variables related to the
      risk of partner-perpetrated violence, but the presence of these macro-level
      variables in the models modified the relationships of the individual-level
      variables to the risk of violence. CONCLUSIONS: Two-level models that include
      individual- and community-level factors may be beneficial for purposes of
      explanation in public health research.

PMID- 7625503
TI  - Spermicide acceptability among patients at a sexually transmitted disease clinic
      in Zambia.
AB  - OBJECTIVE: This study assessed the acceptability of three nonoxynol-9 spermicides
      among persons attending a sexually transmitted disease clinic in Lusaka, Zambia.
      METHODS: Spermicidal foam, suppositories, and foaming tablets were evaluated.
      Women (n = 114) and men (n = 150) attending an sexually transmitted disease
      clinic were enrolled. After each participant used two products, each for 2 weeks,
      consistency of use and acceptability were evaluated. RESULTS: At admission, most
      women (74%) and men (58%) were not using any family planning method. Moreover,
      most women (85%) and men (98%) had at least one sexually transmitted disease or
      genital infection. During the study, the proportion of coital episodes protected
      by spermicide use was high, yet loss to follow-up and discontinuation were also
      substantial. Discontinuation was frequently unrelated to acceptability. Women and
      men rated all three products positively along several acceptability parameters.
      Foam was the least desirable delivery system due to excess messiness.
      CONCLUSIONS: The results of this study suggest that it is feasible to distribute
      spermicides to women and men at increased risk for sexually transmitted disease
      and that the products will be used. Further research should be done among
      different populations and include other spermicidal delivery mechanisms.

PMID- 7625504
TI  - Syphilis and gonorrhea in Miami: similar clustering, different trends.
AB  - During the second half of the 1980s, Miami had a syphilis epidemic while
      gonorrhea rates decreased. To determine whether the direction of these trends
      truly differed within all population subgroups or whether they resulted from
      aggregating groups within which trends were similar, records from four sexually
      transmitted disease clinics from 1986 to 1990 and census data from 1990 were used
      to compare race-, sex-, age-, and zip code-specific groups. Syphilis and
      gonorrhea clustering was similar; 50% of cases occurred in the same zip codes,
      representing 10% of the population. In all groups, gonorrhea decreased (aggregate
      48%) while syphilis first increased (aggregate 47%) and then decreased.
      Determining reasons for these different trends may facilitate controlling these
      diseases.

PMID- 7625505
TI  - Form of day care and respiratory infections among Finnish children.
AB  - The relationship between respiratory infectious diseases and form of day care was
      assessed in a retrospective cohort study of 2568 randomly selected children aged
      1 through 7 years in Espoo, Finland. Day-care center children had an increased
      risk for the common cold, acute otitis media, and pneumonia. The risk
      concentrated in 1-year-old children, for whom the adjusted relative risks
      (incidence density ratios) for the common cold, otitis media, and pneumonia were
      1.69 (95% confidence interval [CI] = 1.43, 2.01), 1.99 (95% CI = 1.57, 2.52), and
      9.69 (95% CI = 2.31, 40.55), respectively. Among 1-year-old children, the
      proportion of infections attributable to care at day-care centers were 41% (95%
      CI = 30, 50) for colds, 50% (95% CI = 36, 60) for otitis media, and 85% (95% CI =
      57, 98) for pneumonia. The results provide evidence that care in day-care centers
      is a determinant of acute respiratory infections in children under 2, whereas
      family day care does not essentially increase risk.

PMID- 7625506
TI  - The classification of AIDS cases: concordance between two AIDS surveillance
      systems in Italy.
AB  - This study assessed the concordance between the transmission classification of
      725 acquired immunodeficiency syndrome (AIDS) cases by the Italian AIDS Registry
      (the national surveillance system) and the classification of the same cases by
      the Italian Cooperative Group on AIDS-Related Tumors. A high degree of
      concordance emerged for intravenous drug users in both sexes (kappa = 0.88; 95%
      confidence interval [CI] = 0.84, 0.92), for homosexual men (kappa = 0.83; 95% CI
      = 0.79, 0.87), and for persons infected through contaminated blood or blood
      derivatives (kappa = 1.00). The concordance was lower among heterosexual men
      (kappa = 0.51; 95% CI = 0.37, 0.65) and especially among men whose risk group was
      not determined (kappa = 0.28; 95% CI = 0.12, 0.44). The discrepancies observed
      among heterosexual men indicate a need for continuing and accurate monitoring of
      AIDS reporting by transmission category.

PMID- 7625507
TI  - Hospitalizations for near drowning in California: incidence and costs.
AB  - California hospital discharge data for 1991 were examined to describe persons
      hospitalized for near drownings (i.e., a submersion incident for which the victim
      was admitted to a hospital). Among residents with near-drowning injuries, there
      were 865 discharges, regardless of outcome (rate = 2.8/100,000); 785 persons
      survived the hospitalization, and 80 (9%) did not. Swimming pools were the most
      common submersion site (62%). Highest rates per 100,000 were found among males
      (3.6), Blacks (3.6), and children 1 through 5 years old (18.4). Charges for the
      initial hospitalization (excluding physicians' fees) amounted to $11.4 million.
      The state government's share of these charges was $5.4 million, with Medi-Cal
      expected to pay $4.1 million. Blacks, males, Medi-Cal recipients, and young
      children are most at risk and should be targeted for prevention programs.

PMID- 7625508
TI  - Syphilis in the South: rural rates surpass urban rates in North Carolina.
AB  - We studied primary and secondary syphilis rates in North Carolina for 1985
      through 1993 to elucidate demographic trends and the role of rurality in the
      state's high rates. Each of the state's 100 counties was classified by rural
      urban character; and county-level rates, adjusted for gender, race, and age
      group, were compared. Syphilis rates rose dramatically during the 9-year period,
      with most of the increase occurring among women, non-Whites, and rural counties.
      The rural rates recently surpassed urban rates, with the greatest increase
      experienced by non-White rural women. The exchange of sex for drugs and
      characteristics of rural poverty may be fueling these trends.

PMID- 7625509
TI  - The estimated frequency of cosmetic breast augmentation among US women, 1963
      through 1988.
AB  - Estimates ranging from 1 to 2 million have been used to describe the number of
      women in the United States who have had cosmetic breast implants. Original data
      from a historical cohort study of women with breast augmentation were combined
      with simulation techniques to compute new estimates grounded on a more objective
      set of information and assumptions than previous attempts. It was estimated that
      the number of women who had cosmetic augmentation mammoplasty between 1963 and
      1988 was 894,206 (range = 437,602 to 2,035,783). The number of women ever treated
      with cosmetic augmentation mammoplasty may be substantially smaller than
      previously reported.

PMID- 7625510
TI  - A matter of opinion about hysterectomies: experts' and practicing community
      gynecologists' ratings of appropriateness.
AB  - The degree to which national expert panel survey ratings of the appropriateness
      of hysterectomy differed from those of a random sample of practicing community
      gynecologists was determined. Community gynecologists rated hysterectomy as more
      appropriate on six of eight cervical dysplasia scenarios. Experts agreed among
      themselves on 19 of 32 indications (intraclass correlation coefficient = 0.66);
      community gynecologists agreed on 12 of 32 indications (intraclass correlation
      coefficient = 0.50). Although few differences of opinion existed between experts
      and community gynecologists, for common clinical scenarios there was a large
      variation of opinion about the appropriateness of hysterectomy within each group.
      For areas of clinical uncertainty in which experts' opinions are used in
      guideline development, additional measures such as process of care, quality of
      life, and patient preference should be included in discussions about guidelines.

PMID- 7625512
TI  - Women's receptivity to testing for a genetic susceptibility to breast cancer.
AB  - Four hundred eighty-four patients undergoing mammography and 498 patients
      visiting their obstetrician-gynecologist were asked whether they would take a
      breast cancer 1 (BRCA1) test to detect a genetic susceptibility to breast cancer.
      More than 90% in both groups said they would take the test. Women were more
      likely to accept if they were regularly having breast examinations by a
      physician, believed that mammography effectively detects early breast cancer, and
      believed that early breast cancer is curable. If shown to have inherited a
      susceptibility, many reported that they would be very anxious, would want the
      test repeated, would examine their breasts more often than monthly, and would
      want mammography more often than yearly. Many also reported that they would
      recommend testing to relatives.

PMID- 7625511
TI  - Hormonal replacement therapy and morbidity and mortality in a prospective study
      of postmenopausal women.
AB  - We assessed the association of hormonal replacement therapy with mortality and
      incidence of multiple diseases in over 40,000 postmenopausal women followed for 6
      years as part of the Iowa Women's Health Study. Compared with women who never
      used hormone replacement therapy, current users had multivariate adjusted
      relative risks (RR) as follows: total mortality (RR = 0.78; 95% confidence
      interval [CI] = 0.65, 0.94), coronary heart disease mortality (RR = 0.74; 95% CI
      = 0.48, 1.12), endometrial cancer incidence (RR = 4.3; 95% CI = 2.7, 6.9), breast
      cancer incidence (RR = 1.23; 95% CI = 0.99, 1.55), colon cancer incidence (RR =
      0.72; 95% CI = 0.46, 1.12), and hip fracture incidence (RR = 0.53; 95% CI = 0.31,
      0.91).

PMID- 7625513
TI  - Mortality rates among 15- to 44-year-old women in Boston: looking beyond
      reproductive status.
AB  - Mortality rates were examined for Boston women, aged 15 to 44, from 1980 to 1989.
      There were 1234 deaths, with a rate of 787.8/100,000 for the decade. Leading
      causes were cancer, accidents, heart disease, homicide, suicide, and chronic
      liver disease. After age adjustment, African-American women in this age group
      were 2.3 times more likely to die than White women. Deaths at least partly
      attributable to smoking and alcohol amounted to 29.8% and 31.9%, respectively.
      Mortality was found to be related more directly to the general well-being of
      young women than to their reproductive status, and many deaths were preventable.
      African-American/White disparities were most likely linked to social factors.
      These findings suggest that health needs of reproductive-age women transcend
      reproductive health and require comprehensive interventions.

PMID- 7625514
TI  - Adolescent parity and infant mortality, Minnesota, 1980 through 1988.
AB  - The association of parity and infant mortality was studied using linked birth
      death files for 46,985 infants born to 11- to 19-year-old Minnesota residents
      between 1980 and 1988. Compared with infants of primiparas, infants of multiparas
      were at twice the risk for infant and postneonatal death but at no increased risk
      for neonatal death. They were also at two to three times the risk for deaths due
      to accidents, infections, and sudden infant death syndrome. The higher
      sociodemographic disadvantage and poorer prenatal care of multiparas did not
      explain the excess infant mortality risk that was concentrated in causes of death
      that are potentially preventable through primary care and parent education.

PMID- 7625515
TI  - Using ICD-9 codes to identify indications for primary and repeat cesarean
      sections: agreement with clinical records.
AB  - Aggregate databases are increasingly being used to evaluate appropriateness of
      care, and, for cesarean sections, Anderson and Lomas' International
      Classification of Diseases, 9th Revision (ICD-9), coding hierarchy is a widely
      used tool. The aim of this study was to assess the validity of the hierarchy and
      expand its applicability to repeat cesareans. Hospital records of 1885 singleton
      cesareans were reviewed. Clinical indications and ICD-9 hierarchical codes were
      concordant for 83% of primary and 86% of repeat cesareans; modification allowed
      elective repeat cesareans to be distinguished from indicated procedures. The
      Anderson and Lomas ICD-9 hierarchy is a valid tool for assessing indications for
      cesarean. The current modification improves its clinical utility and expands its
      application to repeat procedures.

PMID- 7625516
TI  - The epidemiology of vulvovaginal candidiasis among university students.
AB  - Vulvovaginal candidiasis affects approximately 20% of women annually, but it is
      not well characterized epidemiologically. Of 1027 respondents to two mailed cross
      sectional surveys at a large university, 37.5% reported a prior clinical
      diagnosis of vulvovaginal candidiasis. The frequency of first diagnosis increased
      rapidly after age 17, with an estimated 54.7% of women experiencing the condition
      by age 25. In a proportional hazards model of age at first diagnosis,
      vulvovaginal candidiasis was associated with initiation of sexual activity (rate
      ratio [RR] = 2.9; 95% confidence interval [CI] = 2.2, 3.8), oral contraceptive
      use (RR = 1.7; CI = 1.4, 2.2), and White (RR = 3.1; CI = 1.7, 5.7) and Black (RR
      = 5.9; CI = 3.0, 11.5) race vs Asian.

PMID- 7625518
TI  - Risk factors for homelessness among women with schizophrenia.
AB  - A study of risk factors for homelessness among the severely mentally ill was
      extended to include women, and a case-control study of 100 indigent women with
      schizophrenia meeting criteria for literal homelessness and 100 such women with
      no history of homelessness was conducted. Subjects were recruited from shelters,
      clinics, and inpatient psychiatric programs in New York City. Clinical
      interviewers used standardized research instruments to probe three domains of
      risk factors: severity of mental illness, family background, and prior mental
      health service use. Findings adjusted for ethnicity revealed that homeless women
      had higher rates of a concurrent diagnosis of alcohol abuse, drug abuse, and
      antisocial personality disorder. Homeless women also had less adequate family
      support.

PMID- 7625517
TI  - Retaining cocaine-abusing women in a therapeutic community: the effect of a child
      live-in program.
AB  - A clinical trial examined whether retention of cocaine-abusing women in a
      therapeutic community can be improved by permitting their children to live with
      them during treatment. Fifty-three women were randomly assigned to either the
      standard community condition (n = 22), in which children were placed with the
      best available caretaker, or the demonstration condition (n = 31), in which one
      or two of the children lived with their mother in the community. Survival
      analysis distributions indicated that demonstration women remained in treatment
      significantly longer than standard treatment women. (Mean length of stay was
      300.4 days vs 101.9 days, respectively.)

PMID- 7625519
TI  - The rise of the modern addict.
AB  - In the mid-19th century, most American addicts were genteel women hooked on
      opiates through medical treatment. Within a few decades, a new group of addicts
      emerged--pleasure users who patronized opium dens. As local laws closed dens, the
      pleasure users--most often poor young men in northern cities--began experimenting
      with cocaine and heroin, causing an alarmed government to launch an escalating
      campaign to root out the new deviant subculture. Various treatment efforts were
      instituted, from short-lived clinics to federal narcotics farms. This drug use
      epidemic peaked in the 1920s and was essentially quelled by World War II. This
      paper briefly discusses differences between early British and US policies and the
      contemporary implications of this early drug use epidemic.

PMID- 7625520
TI  - War injuries among children in Karlovac District, Croatia.

PMID- 7625521
TI  - Trauma-related care among the uninsured in Massachusetts.

PMID- 7625522
TI  - Monitoring community health workers' performance through lot quality-assurance
      sampling.

PMID- 7625523
TI  - The nursing profession and physicians in authority roles.

PMID- 7625524
TI  - Measuring and reducing exposure to the pollutants in house dust.

PMID- 7625525
TI  - Reducing smoking among psychiatric inpatients: a survey of psychiatrists.

PMID- 7625526
TI  - Paternal smoking and low birthweight: the routes of exposure.

PMID- 7625527
TI  - Isolation of a newly recognized alphavirus from mosquitoes in Vietnam and
      evidence for human infection and disease.
AB  - During studies of arboviral epidemiology in Vietnam, five virus isolates were
      recovered from Culex tritaeniorhynchus mosquitoes. Three of the five isolates
      were identified as strains of Japanese encephalitis virus, but the others,
      collected at Me Tri village, Hanoi, were shown to represent an alphavirus, for
      which we propose the name Me Tri virus. This newly recognized virus is most
      closely related to Semliki Forest virus. The two isolates appear to be antigenic
      subtypes of a single virus, and each was associated with central nervous system
      illnesses in children. Serologic surveys indicate widespread distribution of
      these viruses in both humans and livestock in Vietnam. We suggest that Me Tri
      virus is an etiologic agent of human disease in southeast Asia.

PMID- 7625528
TI  - Development of a species-diagnostic polymerase chain reaction assay for the
      identification of Culex vectors of St. Louis encephalitis virus based on
      interspecies sequence variation in ribosomal DNA spacers.
AB  - Culex pipiens complex mosquitoes (Cx. p. pipiens and Cx. p. quinquefasciatus) are
      among the principal vectors of St. Louis encephalitis (SLE) virus in the eastern
      United States; Cx. restuans and Cx. salinarius play secondary roles in the
      transmission and maintenance of the virus cycle. Accurate identification of these
      three species in field collections is required for epidemiologic studies of SLE
      virus transmission. We have developed a polymerase chain reaction (PCR) assay for
      this purpose. Species-specific PCR primers were designed based on interspecies
      nucleic acid sequence variation in the first and second internal transcribed
      spacers (ITS1 and ITS2) of the nuclear ribosomal DNA gene array; however,
      insufficient variation was detected to differentiate between subspecies of the
      Cx. pipiens complex. The primers were used together in a single amplification
      reaction to correctly identify specimens to species using genomic DNA extracted
      from whole individual mosquitoes, DNA from triturated mosquito pools, or crude
      DNA from mosquito heads or legs.

PMID- 7625529
TI  - In vivo evaluation of immune responses in leishmaniasis: the use of cross-species
      leishmanin preparations for skin testing.
AB  - Skin test reactivity to two commercial preparations of Leishmania major
      leishmanin was evaluated in leishmaniasis patents from Ethiopia (L. aethiopica)
      and Nicaragua (probably L. braziliensis complex). The purpose of using different
      preparations of L. major was to evaluate whether L. major skin test antigens
      could generally be used to detect leishmaniasis due to L. aethiopica and L.
      braziliensis. One preparation was superior in identifying the majority (83-90%)
      of confirmed cases of local cutaneous leishmaniasis (LCL) from Ethiopia. In vitro
      responses to promastigotes of Leishmania spp. correlated well with leishmanin
      positivity to this preparation. The skin test antigen, which performed less well
      (showing a positive result in only 50% of the LCL patients), showed promise when
      used to test active and cured cases of leishmaniasis in Nicaragua (positive
      result in 92% of the active and cured patents). Cross-reacting Leishmania spp.
      may be considered for use in the preparation of standardized leishmanin antigen;
      however, differences in the commercial preparation or the diluent in which the
      parasites are prepared may affect antigenicity and thus its efficacy in detecting
      different forms of leishmaniasis in different geographic areas.

PMID- 7625530
TI  - How many stool examinations are necessary to detect pathogenic intestinal
      protozoa?
AB  - Recent reports have suggested that examination of one stool specimen is
      sufficient to detect protozoa in symptomatic patients. To verify this hypothesis,
      we examined specimens submitted to the regional laboratory of a large, prepaid
      health plan that provides primary care to a membership representative of the
      general population in northern California. We examined the number and results of
      stool specimen examinations in the two-month period before detection of Entamoeba
      histolytica in 125 infected persons, of Giardia lamblia in 154 infected persons,
      and of Dientamoeba fragilis in 60 persons infected with this parasite. About 13%
      of the entire group had a single stool specimen examined, 19% had two examined,
      65% had three examined, and 6% had more than three examined. Most infections were
      detected in the first specimen or specimens submitted, but many were not detected
      until later examination. Thirteen patients with E. histolytica (10.4%) required 4
      9 examinations. The sensitivity of one examination was compared with that of
      three examinations; with the additional examinations, the yield increased 22.7%
      (95% confidence interval [CI] = 11.8-33.5%) for E. histolytica, 11.3% (95% CI =
      6.9-81.8%) for G. lamblia, and 31.1% (95% CI = 17.7-54.4%) for D. fragilis. Our
      results suggest that a single stool specimen examination will miss many
      pathogenic protozoan infections in symptomatic persons.

PMID- 7625531
TI  - Diagnosis of canine visceral leishmaniasis with a dot-enzyme-linked immunosorbent
      assay.
AB  - The maintenance and transmission of human visceral leishmaniasis in an endemic
      area usually requires a mammalian reservoir. Though universal reservoir
      elimination has previously been effective in controlling this disease in
      countries where the primary reservoir is the dog, selective elimination would be
      preferable. To guide this selection process, we performed a prospective, single,
      blind, cohort study evaluating the dot-enzyme-linked immunosorbent assay (dot
      ELISA) in 130 canines from both endemic and nonendemic areas. The results were
      compared with blinded bone marrow aspirate examination and physical assessment of
      the animals. Using visualization of amastigotes on bone marrow examination as a
      priori evidence of infection, the dot-ELISA was found to be highly sensitive
      (97%) and specific (100%). In contrast, the physical evaluation had remarkably
      low sensitivity and specificity. The dot-ELISA is an excellent test for detection
      of the canine reservoir of Leishmania. Because it is simple to perform,
      inexpensive, and highly accurate, it may help control this debilitating illness
      by facilitating selective canine elimination.

PMID- 7625532
TI  - Effectiveness of a dot-blot immunoassay of anti-Rickettsia tsutsugamushi
      antibodies for serologic analysis of scrub typhus.
AB  - We compared a commercially available dot-blot immunoassay system with the
      indirect immunofluorescence assay (IFA) in tests of known negative and known
      positive sera from scrub typhus cases. Using a panel of 100 sera from patients
      with various rickettsial and nonrickettsial infections, we observed that the IFA
      was 99% specific and the dipstick assay was 98% specific. In tests of 91 sera (30
      negative and 61 positive for scrub typhus antibodies) from a study of febrile
      patients in Malaysia, using the standard of an IFA titer < 1:64 as negative, an
      IFA titer > 1:128 as positive, and an IFA titer = 1:64 as either positive or
      negative (supported by clinical records), dipsticks were 83% specific and 90%
      sensitive. The quantitative correlation of the dipsticks to IFA titers was
      confirmed by significant differences in geometric means of inverse IFA titers
      corresponding to the number of positive dipstick spots (no dots = 8.5, one dot =
      43.3, two dots = 206.7, and three dots = 676.9). The assay would enable
      physicians and public health workers who deal with patients to quickly diagnose
      and appropriately treat most cases of the disease, especially in areas of high
      prevalence where the proportion of false-positive results to true-positive
      results would be low.

PMID- 7625533
TI  - Activity of pentostam (sodium stibogluconate) against cutaneous leishmaniasis in
      mice treated with neutralizing anti-interferon-gamma antibody.
AB  - Studies with Leishmania donovani in the mouse have demonstrated that an intact T
      cell compartment is required for effective anti-leishmanial therapy using
      pentavalent antimony compounds such as Pentostam (sodium stibogluconate),
      suggesting that the in vivo efficacy of drug treatment is at least partially
      immune-based. Similarly, Leishmania-infected, immunodeficient human patients
      including those with acquired immunodeficiency syndrome (AIDS) generally relapse
      following therapy with antimonials. However, sodium stibogluconate is directly
      parasiticidal in vitro, in the absence of T cells or T cell products. Using a
      model of a cutaneous form of leishmaniasis, in which susceptible BALB/c mice were
      infected with Leishmania major, we investigated whether the antileishmanial
      activity of the drug demonstrated a requirement for interferon-gamma (IFN-gamma),
      a cytokine produced during a T helper cell type 1 (Th1) immune response and known
      to contribute to resistance to infection, and whether drug therapy affected the
      nature of the antileishmanial response. Lesion development was suppressed in mice
      treated from the onset of infection with sodium stibogluconate alone, and in
      animals treated with sodium stibogluconate plus a neutralizing anti-IFN-gamma
      antibody, and tissue parasite burdens were approximately 10,000-fold less at the
      end of therapy in both groups compared with controls. Lesion development was
      similarly suppressed in mice with established lesions treated with either sodium
      stibogluconate alone, or sodium stibogluconate plus anti-IFN-gamma antibody. The
      production of IFN-gamma by cells from infected animals was somewhat increased
      immediately following therapy with sodium stibogluconate, an effect that was not
      long-lasting, while interleukin-4 (IL-4) production was not affected by
      treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7625534
TI  - Short report: diminished susceptibility to praziquantel in a Senegal isolate of
      Schistosoma mansoni.
AB  - There is a recent report of low efficacy of praziquantel (PZQ) treatment of human
      schistosomiasis in a new Schistosoma mansoni focus in northern Senegal.
      Biomphalaria pfeifferi snails with patent infections were collected from the area
      of the focus and transported to the United Kingdom. Groups of mice were infected
      with cercariae from this Senegalese isolate, or with laboratory-maintained Kenyan
      or Puerto Rican isolates. In two separate experiments, PZQ was less effective
      against the parasite from Senegal than against the two other geographic isolates.
      The reduced susceptibility of S. mansoni to PZQ in infected human populations has
      important implications for current schistosomiasis control programs.

PMID- 7625535
TI  - Effect of repeated treatments with ivermectin on the incidence of onchocerciasis
      in northern Cameroon.
AB  - Mass treatments with ivermectin have been undertaken each year since 1987 in an
      area hyperendemic for onchocerciasis in northern Cameroon. The impact of these
      successive treatments on the incidence of infection in humans was evaluated by
      comparing the prevalence of skin microfilariae (PMF) and the mean microfilarial
      skin densities (MFD) observed in 1987 and 1992 in 5-7-year-old children who had
      never taken the drug but who were members of the treated communities. In 1992,
      the PMF and the MFD in children in this age group who never received ivermectin
      were reduced by 55% and 77%, respectively, in comparison with the values observed
      in 1987, before the first treatment round. These results reflect a pronounced
      reduction in the intensity of the transmission of Onchocerca volvulus in the
      treatment zone. The influence of the ivermectin treatment coverage in the human
      population, as well as the vectorial capacity and the dispersal of the vector
      blackflies, on the transmission of onchocerciasis is discussed.

PMID- 7625536
TI  - An outbreak of acute hepatic encephalopathy due to severe aflatoxicosis in
      Malaysia.
AB  - In October 1988, 13 Chinese children died of acute hepatic encephalopathy in the
      northwestern state of Perak in peninsular Malaysia. The acuteness of the illness
      differed from previously reported outbreaks described in Kenya, India, and
      Thailand. Epidemiologic investigations determined that the children had eaten a
      Chinese noodle, loh see fun, hours before they died. The attack rates among those
      who had eaten the noodles were significantly higher than those who had not (P <
      0.0001). The cases were geographically scattered in six towns in two districts
      along the route of distribution of the noodle supplied by one factory in Kampar
      town. Aflatoxins were confirmed in postmortem samples from patients. This
      outbreak has important public health implications for many developing countries.

PMID- 7625537
TI  - Genetic changes in the population of Plasmodium falciparum in a Sudanese village
      over a three-year period.
AB  - The prevalence of alleles of genes of the Plasmodium falciparum population of
      Asar village in eastern Sudan was monitored over three consecutive years. The
      characters studied were parasite surface antigens, proteins detected by two
      dimensional polyacrylamide gel electrophoresis, enzymes, and drug response.
      Fluctuations in allele prevalences from one year to another were detected and are
      discussed in the context of seasonality of malaria transmission in the region
      studied.

PMID- 7625538
TI  - Leishmaniasis in Texas: prevalence and seasonal transmission of Leishmania
      mexicana in Neotoma micropus.
AB  - The annual prevalence of Leishmania mexicana in Neotoma micropus from 16 southern
      Texas localities was determined by screening 192 N. micropus using in vitro
      culture. Eight woodrats also were screened using the polymerase chain reaction
      (PCR). Forty-six Sigmodon hispidus from four localities were also tested.
      Seasonal transmission was investigated through trap-recapture studies at three
      localities and analysis of infections in juveniles. Fourteen N. micropus from
      four localities were culture-positive for L. mexicana, indicating an annual non
      zero prevalence at these localities of 5.6-27%. Four additional infections at two
      foci were detected only by the PCR. Transmission occurred in the fall in each
      case in which season of transmission could be determined. No S. hispidus were
      positive. These data support the hypothesis that N. micropus is a reservoir of L.
      mexicana in Texas.

PMID- 7625539
TI  - High proportion of subclinical Plasmodium falciparum infections in an area of
      seasonal and unstable malaria in Sudan.
AB  - In the present longitudinal study, a cohort (n = 98) of children and adults 5-30
      years of age living in an area of highly seasonal and unstable malaria
      transmission were followed for malaria morbidity during several successive
      transmission seasons. Based on morbidity surveillance during 1993 and
      measurements of antibody titers to the Plasmodium falciparum ring-infected
      erythrocyte surface antigen (Pf155/RESA), the cohort was divided into three
      groups: those who had at least one episode of clinical malaria (Group 1, n = 31),
      those who did not suffer from clinical malaria but had (Group 2, n = 63) or had
      not (Group 3, n = 4) a significant increase in antibody titers against the
      Pf155/RESA antigen. This increase was defined as equal to or greater than a four
      fold increase in antibody titer in samples from same individuals taken at the
      beginning and the end of the malaria transmission season. Such increases in
      specific antibody levels suggested that the donors had been exposed to a P.
      falciparum blood-stage infection. Measurements of antibody titers to a peptide
      derived from the glutamate-rich protein exoantigen gave data parallel to those
      for Pf155/RESA. A surprisingly high fraction of individuals in the study cohort
      (approximately 66%) showed evidence of infection without ensuing clinical disease
      (Group 2).

PMID- 7625540
TI  - Risk factors for development of first symptomatic Giardia infection among infants
      of a birth cohort in rural Egypt.
AB  - Giardia infection is associated with diarrheal diseases among infants and young
      children in both industrialized and developing countries. A study was conducted
      to demonstrate the predisposing factors for occurrence of the first symptomatic
      Giardia infection among infants in rural Egypt. The study cohort was followed
      from birth through the first year of life. Univariate and multivariate analyses
      of data revealed that infants less than six months of age were at special risk
      for developing their first symptomatic infection compared with infants more than
      six months of age. Analysis of the data, furthermore, revealed an increased risk
      of infant Giardia infection associated with living in a household without a
      latrine (relative risk [RR] = 2.63, confidence interval [CI] = 1.4-4.9, P <
      0.05), a mud floor in the sleeping rooms (RR = 1.79, CI = 1.O30-3.0, P < 0.05),
      and household exposure to more than 10 chickens (RR = 2.5, CI = 1.13-5.56, P <
      0.05). In contrast, the mother's education beyond the primary level (RR = 0.28,
      CI = 0.09-0.85, P < 0.05), drinking water stored in metallic containers (RR =
      0.33, CI = 0.11-0.98, P < 0.05), and male sex (RR = 0.52, CI = 0.3-0.89, P <
      0.05) were associated with decreased risk of Giardia infection. These data
      suggest that in addition to age of infants, poverty, low education, gender
      discrimination, and certain environmental conditions potentiated the risk for
      developing the first symptomatic infection.

PMID- 7625541
TI  - Dengue fever in U.S. troops during Operation Restore Hope, Somalia, 1992-1993.
AB  - Dengue fever (DF) was considered to be a potential cause of febrile illness in
      U.S. troops deployed to Somalia during Operation Restore Hope in 1992-1993. A
      prospective study of hospitalized troops with fever and a seroepidemiologic
      survey of 530 troops were conducted. Among 289 febrile troops hospitalized, 129
      (45%) did not have an identified cause of their fever. Dengue (DEN) virus was
      recovered from 41 (43%) of 96 of these patients by inoculation of admission sera
      into C6/36 cell cultures. Thirty-nine (41%) of the isolates were identified as
      DEN-2 and two (2%) as DEN-3 by an indirect immunofluorescent antibody assay. An
      additional 18 (49%) of 37 culture-negative cases were shown by immunoglobulin M
      (IgM) antibody capture enzyme-linked immunosorbent assay to have anti-DEN virus
      antibody. All identified DF cases recovered within 1-2 weeks; no case of dengue
      hemorrhagic fever or shock syndrome was observed. A seroepidemiologic survey of a
      unit (n = 494) with 17 culture or serologically identified DF cases and a 13%
      attack rate of unidentified febrile illness revealed a 7.7% prevalence of anti
      DEN virus IgM antibody. Failure to use bed nets was the only identified risk
      factor for DEN infection (adjusted odds ratio = 2.2, 95% confidence interval =
      1.4-3.0). These data indicate that DF was an important cause of febrile illness
      among US troops in Somalia, and demonstrate the difficulties in preventing DEN
      infection in troops operating in field conditions.

PMID- 7625542
TI  - Two possible mechanisms for survival and initiation of Murray Valley encephalitis
      virus activity in the Kimberley region of Western Australia.
AB  - Two possible mechanisms are described for the initiation of Murray Valley
      encephalitis (MVE) virus activity in arid, epizootic regions of tropical
      Australia. Virus isolations were made from mosquitoes trapped shortly after the
      first heavy wet season rains and flooding in the east Kimberley, which followed
      approximately nine months of drought. A number of isolates of MVE virus were
      obtained, including isolates from pools of blood-engorged Culex annulirostris
      mosquitoes and from a single pool of male Aedes tremulus mosquitoes. The results
      strongly suggested that MVE virus activity was due both to its introduction in
      viremic vertebrate hosts, from which first-generation mosquitoes became infected
      following blood meals, and also to reactivation of vertically transmitted virus
      from desiccation-resistant eggs of Ae. tremulus. Both mechanisms are discussed
      with respect to environmental conditions.

PMID- 7625543
TI  - Morphometric study of the corpus callosum in Fukuyama type congenital muscular
      dystrophy by magnetic resonance imaging.
AB  - The corpus callosum (CC) of 24 Fukuyama type congenital muscular dystrophy (FCMD)
      patients were studied using midsagittal MRI and the results were compared with
      those of 20 age-matched controls. The measurements included the thickness of the
      genu, body and splenium; the length, height and five specific angles of the CC.
      The cephalic index was also measured on axial MRI. The correlations among CC
      length, CC height, the five angles and the cephalic index were evaluated. One
      case of FCMD was found to have CC agenesis. The thickness of the genu, body,
      splenium and CC length were significantly reduced in FCMD. In addition, in FCMD,
      the CC height was increased, angle alpha was greater, angle delta reduced and the
      CC configuration more rounded, showing a high arch on imaging. No significant
      correlations among CC length, CC height, the five specific angles and the
      cephalic index were found in any of the FCMD data. These observations
      demonstrated the fact that CC development in FCMD is uniquely abnormal, and
      abnormal CC configuration does not have any correlation with altered cephalic
      index.

PMID- 7625544
TI  - Hyperekplexia, a cause of neonatal apnea: a case report.
AB  - We report a case of non-familial hyperekplexia which characteristically developed
      apnea and feeding difficulties in the neonatal period. The abnormal startle
      response was evident from the second week of life onwards. The infant showed a
      marked improvement of the startle response and muscle hypertonia with clonazepam.
      Clobazam was also tried with no apparent response. A prominent long latency C
      response was observed on EMG examination, suggesting a possible cortical neuronal
      hyperexcitability origin for the abnormal startle response observed in
      hyperekplexia.

PMID- 7625545
TI  - Deficiency in complex IV (cytochrome c oxidase) of the respiratory chain,
      presenting as a leukodystrophy in two siblings with Leigh syndrome.
AB  - Two siblings with Leigh syndrome presenting at the age of 6 months with clinical
      and radiological features suggestive of a leukodystrophy are reported. A
      deficiency in complex IV of the respiratory chain (cytochrome c oxidase) was
      demonstrated in muscle mitochondria of both patients. To our knowledge, this is
      the first familial case of Leigh syndrome due to cytochrome c oxidase deficiency,
      presenting clinically and radiologically with signs of a leukodystrophic process.
      We suggest that respiratory chain enzyme defects should be considered in the
      differential diagnosis of cases suggestive of a leukodystrophy.

PMID- 7625546
TI  - Epidermal nevus syndrome with isolated enlargement of one temporal lobe: a case
      report.
AB  - A 5-month-old girl presented with infantile spasms and psychomotor retardation.
      She was born with epidermal nevi on the right side of the head, the right arm and
      the back. MRI of the head showed a right hemimegalencephaly limited to the
      temporal lobe. There were no MRI signs of neocortical dysplasia. Ultrasonography
      revealed multiple cysts in both ovaria and a small solid lesion in the left
      adrenal gland. Hemimegalencephaly represents an overgrowth phenomenon; the
      isolated temporal lobe hypertrophy can be explained as a mild expression of
      hemimegalencephaly. To our knowledge this has not been described before.

PMID- 7625547
TI  - Poliomyelitis-like illness after acute asthma (Hopkins syndrome): a histological
      study of biopsied muscle in a case.
AB  - A case of Hopkins syndrome is presented. The patient was a 4-year-old boy who
      developed weakness of the right leg 2-3 days after a mild asthmatic attack.
      Needle electromyography revealed fasciculation discharges in the right
      gastrocnemius muscle. A histological study of the biopsied right quadriceps
      femoris muscle revealed scattered atrophic fibers, indicating lesions in the
      anterior horn cells of the spinal cord. This is the first reported case of
      Hopkins syndrome including muscle pathology.

PMID- 7625548
TI  - Olivopontocerebellar atrophy: a case report.
AB  - A family with olivopontocerebellar atrophy is presented. Out of 7 siblings two
      male and one female were involved at a similar age of 5 years. Early onset of the
      disease is striking. The index case presented with progressively increasing
      choreiform movements and cerebellar signs. Magnetic resonance imaging morphology
      revealed the diagnosis.

PMID- 7625549
TI  - A further family with epilepsy, dementia and yellow teeth: the Kohlschutter
      syndrome.
AB  - The Kohlschutter syndrome is a very uncommon inherited disorder characterized by
      epilepsy, dementia, and yellow teeth. We present two new patients who contribute
      to an increase in our knowledge of the clinical phenotype of this syndrome. They
      are two siblings born from consanguineous parents. Dysmorphological signs, such
      as broad thumbs, are reported for the first time in association with this
      syndrome, together with neurophysiological peculiarities (occipital evoked
      spikes) and hypoplasia of the cerebellar vermis. The authors suggest that ethnic
      factors might be important and conclude that the clinical phenotype of the
      Kohlschutter syndrome is still in need of further characterization.

PMID- 7625551
TI  - Hyperkinetic behaviour, attention deficit disorder, conduct disorder and
      instabilite psychomotrice: identity, analogies, and misunderstandings. Commentary
      to Gordon's paper (Brain Dev 1994; 15: 169-72).
AB  - 'Hyperkinetic behaviour', 'attention deficit disorder' and 'conduct disorder'
      with antisocial aspects or delinquency are concepts frequently superimposed. They
      can be traced back to the classic nosological entity, 'instabilite
      psychomotrice', still used in French psychiatric nosography. In this paper, the
      different components of the condition are analyzed (emotional, attentional,
      posturo-motoric and behavioural) both in normal subjects and in cases of mild
      encephalopathies, and for different age groups. A criticism is advanced towards
      the undifferentiated approach to the problem in the most current literature.

PMID- 7625550
TI  - Clinical and MRI findings in a case of D-2-hydroxyglutaric aciduria.
AB  - We report the 3rd case in the literature of a 3-year-old boy with D-2
      hydroxyglutaric (D-2-HG) aciduria, who presented primarily generalized hypotonia
      and feeding difficulty during the neonatal period, with eventual development of
      generalized myoclonic seizures. Gas chromatographic analysis of urinary organic
      acids showed persistent excretion of D-2-HG. The clinical manifestations are
      quite similar to those of the 2nd reported case with D-2-HG aciduria. Serial MRI
      performed 1 year and 2 1/2 years after birth demonstrated bilateral symmetrical
      periventricular lesions in the parieto-occipital white matter, which might
      reflect the cortical blindness in our patient.

PMID- 7625552
TI  - Inhibitory period and late muscular responses after transcranial magnetic
      stimulation in healthy children.
AB  - Transcranial magnetic stimulation (TMS) was investigated in 24 healthy children
      between the ages of 3 and 14 years in order to study late muscular responses (as
      they are observed in adults) as a function of age and maturation. Muscular
      responses were recorded bilaterally from the biceps muscle. An early muscular
      response and several late phenomena can be elicited in children. (i) An
      inhibitory period following the primary response could preferentially be recorded
      contralaterally. (ii) During facilitation, a late response was recorded
      bilaterally. (iii) Without facilitation (during 'relaxation'), late responses
      were recorded bilaterally with a latency of between 50-400 ms. The latency of the
      latter responses depended on the age of the children, and may therefore be useful
      in monitoring the maturation of the central motor system in infants. Due to small
      side-to-side differences, the inhibitory period may be of diagnostic value in
      children for detection of unilateral dysfunction of the central nervous system.

PMID- 7625553
TI  - The prevalence of Rett syndrome in Fukui prefecture.
AB  - The present study was performed to estimate the prevalence of Rett syndrome in
      Fukui prefecture by sending questionnaires to special classes (classes for
      handicapped children in schools for normal children) and schools for
      mentally/physically handicapped children, and observing children suspected of
      having this syndrome on the basis of answers to the questionnaire. The subjects
      were girls aged 6-14 years who were attending 11 special classes and 7 schools
      for handicapped children. The prevalence of Rett syndrome was estimated to be
      0.22 per 10,000 girls aged 6-14 years in Fukui prefecture, as of April 1, 1993.
      The prevalence noted in this study was lower than those found in previous studies
      in Japan and Western countries.

PMID- 7625554
TI  - Prenatal diagnosis of infantile neuronal ceroid-lipofuscinosis: a combined
      electron microscopic and molecular genetic approach.
AB  - Based on two unrelated index patients afflicted with INCL, fetal chorion tissues
      were studied from subsequent pregnancies of the two respective mothers resulting
      in the prenatal diagnosis of INCL in two of the three pregnancies. Documentation
      of INCL was based on electron microscopy and DNA studies of the biopsied chorion
      tissue, later confirmed in the two affected fetuses after termination of their
      pregnancies by demonstrating INCL-specific lipopigments in post-mortem tissues,
      in the liver of both aborted fetuses and, additionally, in spleen and skeletal
      muscle of one of the affected fetuses. The autolysis of the aborted tissues,
      however, precluded a systematic documentation of all affected cell types and
      tissues. Thus, prenatal diagnosis of INCL is feasible and reliable for both
      Finnish and non-Finnish families.

PMID- 7625555
TI  - 123I-IMP SPECT findings in mitochondrial encephalomyopathies.
AB  - We performed N-isopropyl-[123I]p-iodoamphetamine (IMP) single photon emission
      computed tomography (SPECT) in three patients with Leigh syndrome, two patients
      with mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes
      (MELAS), and two siblings with progressive external ophthalmoplegia (PEO). The
      SPECT images were compared with the findings on magnetic resonance imaging (MRI)
      and computed tomography (CT). All Leigh syndrome patients showed low accumulation
      areas (LAA) bilaterally in the frontal lobes and the basal ganglia. The frontal
      lobe LAA was seen even in an area without abnormalities on CT/MRI. Each MELAS
      patient showed a focal LAA. SPECT could also detect an old stroke-like lesion
      that was no longer shown by CT/MRI. However, SPECT did not show LAA in the basal
      ganglia, which showed calcification on CT or abnormal signal intensity on MRI.
      MRI in the 2 PEO patients showed lesions bilaterally in the basal ganglia in one,
      and in the internal capsules in the other. SPECT showed LAA not only in
      corresponding areas, but also in the occipital lobes, where no lesions were
      revealed by MRI. Thus, 123I-IMP SPECT was more sensitive than CT/MRI for
      detecting stroke-like lesions in MELAS patients, although it did not detect small
      lesions in the basal ganglia. LAA in the frontal lobes and occipital lobes may be
      SPECT findings characteristic of Leigh syndrome and PEO, respectively.

PMID- 7625556
TI  - Muscle CT scans in preclinical cases of Duchenne and Becker muscular dystrophy.
AB  - Skeletal muscle CT scans were performed in patients with Duchenne (DMD) as well
      as Becker muscular dystrophy (BMD) in the preclinical or early clinical stage, at
      the levels of the 3rd lumbar vertebra, the mid thigh, and the maximum
      circumference of the calf. Only slight intramuscular low density areas and
      muscular atrophy were ascertained on gross visual inspection from the age of 3
      years onward in DMD. However, the mean CT numbers calculated for individual
      muscles clearly decreased with increasing age in all muscles except anterior and
      posterior tibialis, which indicated them to be well preserved. Comparison of the
      rates of decrease in the CT numbers revealed that a rapid change in the
      paravertebral group commenced in the muscles on the lateral side, while among the
      adductors of the thigh, gracilis tended to be comparatively well preserved; this
      is the pattern of muscle involvement characteristic of symptomatic patients. In
      BMD, the atrophic change was extremely slight, and the CT numbers of the muscles
      were higher than the corresponding values for DMD in the same age group. CT
      numbers represent more objective indices for the assessment of muscular lesions
      as compared with gross visual inspection of skeletal muscle CT scans at the
      preclinical stage.

PMID- 7625557
TI  - Effects of acute and repeated ethanol exposures on the locomotor activity of BXD
      recombinant inbred mice.
AB  - Investigations of ethanol's (EtOH's) complex response profile, including
      locomotor and other effects, are likely to lead to a more in-depth understanding
      of the constituents of alcohol addiction. Locomotor activity responses to acute
      and repeated EtOH (2 g/kg, ip) exposures were measured in BXD recombinant inbred
      (RI) mice and their C57BL/6J (B6) and DBA/2J (D2) progenitors. Both the acute
      response and the change in initial EtOH response with repeated treatments were
      strain-dependent. The coefficient of genetic determination was 0.38-0.49 for
      initial locomotor response to EtOH, and 0.29 for change in response. Changes in
      response were largely attributable to sensitization of locomotor stimulation.
      Quantitative trait loci (QTL) analyses identified significant marker associations
      with basal activity, acute locomotor response, and change in response. Markers
      were for QTL on several chromosomes, and there was only one case of overlap in
      marker associations among phenotypes. Acute locomotor response and locomotor
      sensitization were negatively correlated with 3% EtOH preference drinking data
      collected in BXD RI strains. Overall, these results demonstrate locomotor
      sensitization induced by EtOH, suggest independence of genetic determination of
      locomotor responses to acute and repeated EtOH exposure, and partially support a
      relationship between reduced sensitivity to the locomotor stimulant/sensitizing
      effects of EtOH and EtOH consumption.

PMID- 7625558
TI  - Taste reactivity in high alcohol drinking and low alcohol drinking rats.
AB  - High alcohol drinking (HAD) and low alcohol drinking (LAD) rats were tested, in
      three exposures, for taste reactivity to five concentrations of alcohol (5%, 10%,
      20%, 30%, and 40%, v/v), water, and one concentration each of sucrose and
      quinine. Of the three reactivity exposures, one was done before a 3-week period
      of continuous access to water and 10% alcohol, the second test was done
      immediately after the consumption period, and the final reactivity test was done
      after 1 month of alcohol abstinence. The results showed that the groups did not
      differ in reactivity on the initial test. After the consumption tests (when the
      HAD rats consumed significantly more alcohol than the LAD rats), differences in
      reactivity were found: HAD rats produced significantly more ingestive responses
      (which promote consumption) and significantly fewer aversive responses (which
      facilitate fluid rejection) than LAD rats. These differences were maintained even
      after 1 month of alcohol abstinence. The present data replicate an earlier
      experiment with alcohol-preferring (P) rats and alcohol-non-preferring (NP) rats,
      and indicate that the selective breeding process does not produce differences in
      the innate perception of the taste of alcohol. However, after experience with
      drinking alcohol, rats selectively bred for high alcohol consumption exhibit a
      palatability shift reflected by high ingestive responding and little or no
      aversive responding. Such a shift would clearly contribute to the maintenance of
      high levels of alcohol consumption.

PMID- 7625559
TI  - Chronic alcohol intoxication enhances the expression of CD18 adhesion molecules
      on rat neutrophils and release of a chemotactic factor by Kupffer cells.
AB  - Chronic alcohol intoxication has been associated with increased migration of
      inflammatory leukocytes to the liver that may contribute to the development of
      alcoholic hepatitis in susceptible individuals. Thus, this work was performed to
      examine the mechanism by which neutrophils [polymorphonuclear neutrophils (PMNS)]
      are sequestered in the liver during prolonged consumption of alcohol. Male
      Sprague-Dawley rats were fed with Sustacal supplemented by 36% alcohol, or
      isocaloric diet for 16 weeks. Circulating blood PMNs were collected and examined
      for CD18 (beta 2-integrin) adhesion molecule expression. Monoclonal antibody
      1F12, an anti-CD18 antibody and potent neutropenic agent, was used to detect CD18
      on PMNs. More than 97% of neutrophils obtained from pair and ethanol-fed rats
      were positive for the antibody. Fluorescence intensity of fluorescein
      isothiocyanate-1F12 binding to PMNs from ethanol-fed rat was significantly
      enhanced 2-fold compared with the pair-fed controls. The release of
      chemoattractant and free radical-generating activity in culture supernatants of
      Kupffer cells was also examined. Twenty-four hr culture supernatants of Kupffer
      cells from chronic alcoholic rats enhanced the migration and superoxide anion
      generation by normal PMNs, compared with those of the pair-fed rats. Antirat
      interleukin-8 antiserum inhibited chemotactic activity and superoxide generating
      capacity of culture supernatants. These results suggest that upregulation of
      adhesion molecules on PMNs and chemotactic factor release from Kupffer cells may
      contribute, at least in part, to enhanced migration of inflammatory leukocytes to
      the liver during chronic alcohol intoxication.

PMID- 7625560
TI  - Liver sinusoid during chronic alcohol consumption in the rat: an electron
      microscopic study.
AB  - Transmission and scanning electron microscopic studies were performed on the
      liver sinusoid, with emphasis on sinusoidal endothelial cells, in rats fed a
      liquid diet containing either alcohol or dextrin (control) for 14 weeks. Animals
      were also treated with either Gram-negative bacterial lipopolysaccharide (LPS;
      100 micrograms/100 g body weight, intravenously) or sterile saline (control). All
      specimens were prepared after perfusion fixation of the liver. Livers of rats fed
      dextrin-containing liquid diet displayed the ultrastructural features typical of
      the sinusoid and its endothelial cells. Livers from alcohol-fed animals, however,
      were characterized by massive loss of sieve-plate architecture of the sinusoidal
      endothelium, which was virtually replaced with a meshwork of enlarged openings
      with diameters frequently exceeding 1 micron. Morphological evidence of Kupffer
      cell activation could also be seen along with significant fatty infiltration of
      the hepatocyte. Conversely, LPS administration to dextrin-fed animals induced an
      apparent decrease in fenestration of the sinusoidal endothelial cell, accompanied
      by morphological evidence of enhanced endocytotic activity and cytoplasmic
      swelling. The changes seen 3 hr after LPS administration were markedly advanced
      at 24 hr. LPS administration to alcohol-fed rats accentuated the alterations
      observed after alcohol treatment alone. Additionally, the presence of platelets
      in the sinusoid as well as adhering to the hepatocyte microvilli in the space of
      Disse, along with the presence of Ito and Kupffer cell activation, greater than
      that observed in the alcohol-treated rats, is morphological evidence consistent
      with the disruption of vascular integrity in the liver.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7625561
TI  - Use of repeated measures in an analysis of ethanol-induced loss of righting
      reflex in inbred long-sleep and short-sleep mice.
AB  - We present a repeated-measures analysis of ethanol-induced loss of righting
      reflex (LRR) in Inbred Long-Sleep (ILS) and Inbred Short-Sleep (ISS) strains of
      mice and their F1 and F2 cross progeny. Mice were administered a 4.1 g/kg
      intraperitoneal dose of ethanol at two times, 7-10 days apart. Repeatability is
      nonsignificant in ILS, ISS, and F1 mice, but is highly significant (0.47, p <
      0.01) in the F2 mice. Mean LRR does not differ between trials 1 and 2, with the
      exception of the ISS strain in which the interaction of sex with LRR
      sensitization is significant. This two-trial method leads to increased accuracy
      of genotype assessment for pharmacological or behavioral traits where trial 1
      does not influence the outcome of trial 2. The repeated-measures design
      facilitates novel analyses of the duration of LRR, and results suggest that most
      environmental variance for LRR is due to nonreplicable influences.

PMID- 7625563
TI  - Structural analysis of peptide-acetaldehyde adducts by mass spectrometry and
      production of antibodies directed against nonreduced protein-acetaldehyde
      adducts.
AB  - Acetaldehyde can form protein-acetaldehyde adducts (AAs) in vivo and may play a
      role in the genesis of alcoholic liver disease. The nature of the chemical
      modification of proteins by acetaldehyde in vivo has not been elucidated. In
      vitro, acetaldehyde can form reversible adducts including a Schiff's base with
      lysine (K) and imidazolidinone with terminal amino groups of proteins such as
      human hemoglobin (Hb). In this study, we used FAB/MS to analyze the products of
      peptide-AAs (pep-AAs) formed by incubating acetaldehyde with Hb peptides. We then
      used an octabranched multiple antigen peptide (MAP) system containing Hb peptide
      AAs to raise antibodies. Three Hb peptides [i.e., 8-pep consisting of 8 residues
      (V1HLTPVEK8) at the N-terminus of beta-chain of human sickle-cell Hb, 11-pep-gly
      consisting of 11 residues (G56NPKVKAHGKK66) in a segment of beta-chain rich in
      lysine, and 11-pep-pro that consists of the same sequence as 11-pep-gly, except
      G56 was replaced by proline (P)] were incubated with 1 mM acetaldehyde at 4
      degrees C for 7d without NaCNBH3 (nonreduced conditions). Analysis by FAB/MS
      showed that 8-pep formed an imidazolidinone at the N-terminal valine, 11-pep-gly
      formed a Schiff's base and imidazolidinone at the N-terminus, whereas 11-pep-pro
      that lacks a free alpha-amino group formed only a Schiff's base at K59. By
      contrast, incubation of these Hb peptides with 250 mM acetaldehyde and NaCNBH3 at
      37 degrees C for 1 hr (reduced conditions) produced mono- and diethylated
      modifications of all available K residues, as well as the N-terminal amino
      group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7625562
TI  - Alteration of [3H]MK-801 binding associated with the N-methyl-D-Aspartate
      receptor complex by acute ethanol in rat cortex and hippocampus in vitro.
AB  - We investigated the effect of ethanol on specific binding of [3H]MK-801 to the
      intrachannel phencyclidine (PCP) receptor site, as an index of change in the
      functional response of the N-methyl-D-Aspartate (NMDA)-associated ion channel.
      Saturation binding experiments were performed on synaptic membrane homogenates
      from adult rat cortex and hippocampus. [3H]MK-801 binding assays were conducted
      under conditions of basal, 10 microM glutamate, or 10 microM glutamate + 30
      microM D-serine, with and without 50 or 100 mM ethanol. Association experiments
      of [3H]MK-801 binding (5 nM) were conducted under conditions of 0 or 10 microM
      glutamate, with varying concentrations of glycine (0.01, 0.10, and 10 microM)
      with and without 100 mM ethanol. Ethanol (50 and 100 mM) significantly decreased
      the percentage of high-affinity (open-channel state) MK-801 receptors with a
      concomitant increase in percentage of low-affinity receptors, but did not change
      high- and low-affinity constants of the two binding states. An ethanol-induced
      increase in the closed-channel receptor density in basal and activated conditions
      was suggested by the saturation experiments. Association experiments further
      explained this finding, in that ethanol (100 mM) significantly decreased fast
      component (open-channel) [3H]MK-801 binding in conditions of glycine (0.01-10
      microM) only and activated conditions of glutamate + glycine (0.01-0.10 microM).
      However, the observed fast and slow kinetic rate constants of [3h]MK-801 binding,
      as well as total specific binding (fast + slow components), were not
      altered.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7625564
TI  - Differential sensitivity of NMDA receptor-mediated synaptic potentials to ethanol
      in immature versus mature hippocampus.
AB  - Pharmacologically isolated, NMDA receptor-mediated population EPSPs (pEPSPs) were
      evoked from area CA1 of hippocampal slices using electrical stimulation of the
      Schaffer collateral/commissural fiber pathway. Slices were prepared from rats
      aged 20-25 or 80-100 days. The inhibitory effects of a range of ethanol
      concentrations were assessed. While ethanol antagonized NMDA-mediated pEPSPs in
      slices from both age groups, it was significantly more potent against pEPSPs from
      immature versus mature hippocampi. In slices from mature animals, significant and
      consistent reduction of pEPSPs was observed only with the highest ethanol
      concentration (100 mM), whereas 10, 30, or 100 mM significantly reduced the
      amplitude of pEPSPs in slices from immature animals. These results indicate that
      NMDA-mediated synaptic activity in the hippocampus is more sensitive to the
      effects of ethanol in immature versus mature animals.

PMID- 7625565
TI  - Tumor necrosis factor-alpha cell-surface receptors of liver parenchymal and
      nonparenchymal cells during acute and chronic alcohol administration to rats.
AB  - Tumor necrosis factor-alpha (TNF-alpha) has been shown to contribute to the
      alcohol [ethanol (ETOH)]-induced alteration of hepatic function. Therefore we
      tested the hypothesis that the hepatic action of TNF-alpha could be due, at least
      in part, to alterations in TNF-alpha cell-surface receptors of hepatic
      parenchymal (hepatocytes) and nonparenchymal (Kupffer and sinusoidal endothelial)
      cells. Rats were either acutely treated with ETOH by a primed, continuous 7-hr
      intravenous infusion of 20% (w/v) ETOH (30 mg/100 g body weight/h) or chronically
      fed an ETOH-containing liquid diet (5.2% ETOH, w/v, with ETOH as 36% of total
      calories) for 14 weeks. Control rats in the acute group were infused with sterile
      saline, whereas control rats in the chronic group were fed liquid diet containing
      dextrin to replace ETOH in isocaloric amounts. Three hr before killing, the rats
      were injected intravenously with Gram-negative bacterial lipopolysaccharide
      [(LPS) 100 micrograms/100 g body weight] or saline. Hepatocytes, Kupffer cells,
      and sinusoidal endothelial cells were isolated after liver perfusion with
      collagenase (without pronase), separated by centrifugal elutriation, and used to
      determine the affinity (Kd) and capacity (Bmax) of binding sites, using
      recombinant human-[125I]TNF-alpha as the ligand. Two binding sites were detected
      on Kupffer cells and sinusoidal endothelial cells isolated from control animals:
      a high-affinity (Kd1, in the range of 150-200 pM), low-capacity (Bmax, in the
      range of 2-3 fmol/10(6) cells) binding site and a low-affinity (Kd2, in the range
      of 2-9 nM), high-capacity (Bmax2, in the range of 3-15 fmol/10(6) cells) binding
      site.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7625567
TI  - Acetaldehyde-serum protein adducts inhibit interleukin-2 secretion in
      concanavalin A-stimulated murine splenocytes: a potential common pathway for
      ethanol-induced immunomodulation.
AB  - Variable immunobiological changes occur with alcohol consumption. Previous
      studies have shown that acetaldehyde forms stable adducts with serum proteins,
      including albumin. These adducts are elevated in persons and animals consuming
      ethanol. We examined the effect of serum protein-acetaldehyde adducts formed with
      fetal bovine serum (FBS) on concanavalin A-stimulated murine splenocytes.
      Interleukin-2 (IL-2) secretion and IL-2 receptor (IL-2R) expression were
      determined as a function of the effect of the acetaldehyde-protein adduct(s). FBS
      was incubated with acetaldehyde (500, 100, 50, 25, 10, and 0 microM) for 1 hr at
      37 degrees C. Excess acetaldehyde was removed by ultrafiltration using a 500
      molecular weight cut-off membrane in 3 volumes. Free as well as bound
      acetaldehyde was quantified using fluorigenic HPLC before and after incubation.
      Recovered acetaldehyde correlated with the amount added (r2 = 0.996). Splenocytes
      were cultured for 48 hr in complete medium containing 5% acetaldehyde-treated and
      5% untreated FBS with 4 micrograms/ml concanavalin A. Although cell viability was
      unchanged, acetaldehyde-treated FBS mixed with native FBS decreased IL-2
      secretion in a dose-dependent manner. The percentage of cells expressing IL-2R
      was reduced only at the highest acetaldehyde-FBS dose. Therefore, immunological
      effects ascribed to ethanol may result in part from the toxic properties of
      acetaldehyde-protein adducts on IL-2 secretion.

PMID- 7625566
TI  - Effect of ethanol, propanol, butanol, and catalase enzyme blockers on beta
      endorphin secretion from primary cultures of hypothalamic neurons: evidence for a
      mediatory role of acetaldehyde in ethanol stimulation of beta-endorphin release.
AB  - Previously, we have shown that low doses of ethanol (12.5-100 mM) and
      acetaldehyde (12.5-50 microM), but not salsolinol, enhanced immunoreactive beta
      endorphin (IR-beta-EP) secretion from fetal hypothalamic neurons in primary
      culture. In this study, the effects of ethanol, propanol, and butanol, as well as
      the effect of catalase inhibitors on IR-beta-EP secretion were studied in vitro
      to determine the role of membrane fluidization and ethanol metabolism on ethanol
      induced IR-beta-EP secretion. The primary cultures of fetal hypothalamic neurons
      were maintained for 8-9 days in chemically defined medium and treated for 5 hr
      with ethanol (50 mM), propanol (25 and 50 mM), and butanol (25 and 50 mM).
      Determination of hourly secretion of IR-beta-EP from the cultures revealed that
      only 50 mM ethanol caused stimulation of IR-beta-EP secretion, whereas propanol
      and butanol did not alter IR-beta-EP response at any given concentration.
      Pretreatment of these cultures with the catalase inhibitors, 3-amino-1,2,4
      triazole (3-AT; 1, 5, and 10 mM), caused a dose-dependent inhibition of ethanol
      stimulated IR-beta-EP secretion, but did not inhibit dibutyryl cAMP (dcAMP)
      stimulated IR-beta-EP secretion. Another catalase inhibitor, sodium azide (5 mM),
      also inhibited ethanol-stimulated IR-beta-EP secretion. Measurement of
      acetaldehyde production in cultured cells and media after ethanol or dcAMP
      treatments revealed that cultured cells produce acetaldehyde only after ethanol
      treatment and at levels of acetaldehyde (8-24 microM) that are known to evoke IR
      beta-EP release. The catalase inhibitor 3-AT (10 mM) treatment reduced ethanol
      evoked acetaldehyde production.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7625568
TI  - The neurosteroid, 3 alpha-hydroxy-5 alpha-pregnan-20-one, protects against
      bicuculline-induced seizures during ethanol withdrawal in rats.
AB  - Prolonged alcohol consumption leads to the development of tolerance to and
      dependence on ethanol, resulting in a decreased response to the sedative/hypnotic
      effects of ethanol, and by negative symptomatology following abrupt termination
      of use. One symptom associated with ethanol withdrawal in humans, as well as
      laboratory animals, is enhanced susceptibility to seizures. This study
      investigated the effects of the neurosteroid, 3 alpha-hydroxy-5 alpha-pregnan-20
      one (3 alpha-5 alpha-THP), on alterations in seizure sensitivity associated with
      ethanol withdrawal. 3 alpha-5 alpha-THP is a potent anxiolytic and anticonvulsant
      agent that acts via selective interactions with GABAA receptors. Extensive
      evidence suggests that some aspects of ethanol dependence and withdrawal are
      mediated by alterations in GABAA receptor function. Withdrawal from chronic
      ethanol exposure elicited dramatic increases in seizure susceptibility in male
      and female rats. Administration of 3 alpha-5 alpha-THP just before seizure
      threshold determinations blocked the increased seizure susceptibility induced by
      ethanol withdrawal. Ethanol-withdrawn animals were protected by 3 alpha-5 alpha
      THP at a dose that had no effect on control animal seizure thresholds. Moreover,
      male and female rats displayed differential responses to the seizure-threshold
      lowering effects of ethanol withdrawal, as well as the protection by 3 alpha-5
      alpha-THP pretreatment. These findings suggest that there are gender differences
      associated both with ethanol withdrawal as well as the protection by 3 alpha-5
      alpha-THP in ethanol-dependent rats.

PMID- 7625569
TI  - Divergence of ethanol and acetaldehyde kinetics and of the disulfiram-alcohol
      reaction between subjects with and without alcoholic liver disease.
AB  - Despite standardization, marked interindividual variation in the severity of the
      disulfiram-alcohol reaction (DAR) has been observed. We studied the DAR in 51
      consecutive alcoholics with (n = 16) and without (n = 35) significant alcoholic
      liver disease. Clinical signs of the DAR were much weaker in the patients with
      compared with those patients without liver disease. Because acetaldehyde is
      thought to be the main cause of the DAR, we studied ethanol and acetaldehyde
      kinetics in 13 patients (6 females, 7 males) with alcoholic liver disease
      (documented by biopsy, clinical and/or radiological findings, and by quantitative
      liver function) [galactose elimination capacity (GEC) 4.2 +/- SD 1.0 mg/min/kg;
      aminopyrine breath test (ABT) 0.14 +/- 0.10% dose x kg/mmol CO2] and 13 age- and
      sex-matched controls (alcoholics without significant liver disease, GEC 7.1 +/-
      0.7; ABT 0.81 +/- 0.35). Clinical signs of acetaldehyde toxicity during the DAR
      (flush, nausea, tachycardia, and blood pressure drop) were absent in alcoholic
      liver disease, but clearly evident in controls. Blood ethanol kinetics were
      similar in both groups, Cmax and area under the concentration-time curve (AUC)
      being 6.27 +/- 1.82 and 368.9 +/- 72.9 mmol x min/liter in alcoholic liver
      disease, and 6.62 +/- 1.71 and 377.6 +/- 124.5 in controls, respectively. In
      contrast, there was a strong (p < 0.001) difference in Cmax and AUC of
      acetaldehyde, respective values being 33.46 +/- 21.52 and 1463.8 +/- 762.5 mumol
      x min/liter in alcoholic liver disease, and 110.87 +/- 56.00 and 4162.0 +/-
      2424.6 in controls.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7625570
TI  - Decrease in cytochrome P4502E1 as assessed by the rate of chlorzoxazone
      hydroxylation in alcoholics during the withdrawal phase.
AB  - To evaluate cytochrome P4502E1 (CYP2E1) induction in alcoholics, the ratio of the
      concentrations of 6-hydroxychlorzoxazone (6-OH-CHZ) and chlorzoxazone (CHZ) was
      measured in blood 2 hr after CHZ ingestion using a HPLC method. This ratio was
      determined in controls and in alcoholic patients after 1, 2, 3, 4, 5, 8, and 21
      days withdrawal. It was found to be 0.34 +/- 0.03 in 30 controls and 1.05 +/-
      0.14 in 41 alcoholic patients within 2 days following ethanol withdrawal. This
      ratio decreased rapidly during withdrawal as attested by the short half-life of
      CYP2E1, which was found to be 2.5 days. Patients tested for CHZ metabolism after
      8 or 21 days alcohol abstinence displayed the same ratio as controls [0.35 +/-
      0.03 (n = 28) and 0.31 +/- 0.03 (n = 34), respectively]. No correlation was
      observed between gamma-glutamyltransferase, carbohydrate-deficient transferrin
      values, the amount of alcohol consumed/day, and the 6-OH-CHZ/CHZ ratio. There was
      no influence of smoking on the rate of CHZ hydroxylation, because smokers
      displayed the same ratio as nonsmokers [0.33 +/- 0.025 (n = 62) and 0.33 +/- 0.02
      (n = 30), respectively]. The CHZ hydroxylation ratio seems to be a good
      reflection of the hepatic and extrahepatic CYP2E1 activity in humans.

PMID- 7625571
TI  - Alcohol acceptance, preference, and sensitivity in mice. II. Quantitative trait
      loci mapping analysis using BXD recombinant inbred strains.
AB  - Quantitative trait loci (QTL) mapping of complex phenotypes has emerged as an
      important feature of the recombinant inbred (RI) strain methodology. In this
      second study of our series on alcohol-related behaviors in mice, we examine
      alcohol acceptance, preference, and hypnotic dose sensitivity (HDS) to a standard
      dose of alcohol measured in BXD RI strains to identify candidate QTL regions
      responsible for their heritability. We detected highly significant marker
      associations for acceptance on chromosome 12 (Eif4e), for preference on
      chromosome 1 (D1Rti2) and chromosome 7 (D7Mit7), and for HDS on chromosome 7
      (Mpmv1). These are the strongest QTL associations that we detected, but several
      other candidate QTL regions are reported. Given the limited number of BXD RI
      strains available, the large number of markers used herein, and the consequent
      chance of identifying false marker associations, these RI QTL mapping results
      must be seen as tentative, but an important first step toward identifying QTL for
      alcohol-related behaviors.

PMID- 7625572
TI  - Turnover of ethyl-linoleate in rat plasma and its distribution in various organs.
AB  - The fate of [14C]ethyl-linoleate (EthLin) after its intravenous administration
      was investigated in pentobarbital-anesthetized rats. The disappearance of
      [14C]EthLin from the plasma was very rapid and followed quite closely a
      biexponential function of time. Fitting of the experimental data to a two
      compartmental mammillary model revealed that the labeled compounds are eliminated
      from the plasma with a half-life of < 1 min during the early time following the
      intravenous injection and that a large portion of the EthLin is hydrolyzed
      instantly to linoleic acid and ethanol. About 9-11% of the plasma [14C]EthLin or
      its breakdown products are irreversibly cleared from the plasma compartment each
      minute. Most of the 14C-labeled compounds that originated in the plasma were
      recovered in the rat liver and lungs and to a lesser extent in the heart, spleen,
      and kidneys. Two hr after the [14C]EthLin administration, approximately 2.5-5.5%
      of the total radioactivity in the various organs was still associated with
      EthLin. Such accumulations, although relatively small, indicate that fatty acid
      ethyl esters (FAEEs) may be taken up from the plasma. Thus, some of the FAEEs
      that are formed in certain organs may spillover to the circulating blood where
      much of it would be hydrolyzed to free fatty acids, but reuptake from the plasma
      may still account, to some extent, to FAEE-induced damage in chronic alcohol
      abusers.

PMID- 7625573
TI  - Increased cell death and reduced neural crest cell numbers in ethanol-exposed
      embryos: partial basis for the fetal alcohol syndrome phenotype.
AB  - Fetal alcohol syndrome (FAS) is characterized by growth retardation, craniofacial
      malformations, and heart and neural defects; the cellular and molecular
      mechanism(s) responsible for ethanol's teratogenicity remains unknown. Although
      the phenotype suggests that prenatal ethanol exposure perturbs neural crest cell
      development, direct proof that these cells are an in utero target is still
      lacking. Previous research suggested that cranial neural crest cells are
      eliminated by ethanol-induced apoptosis. We tested this hypothesis using a chick
      embryo model of FAS. A single dose of ethanol, chosen to achieve a concentration
      of 35-42 mg/dl, was injected in ovo at gastrulation and resulted in growth
      retardation, craniofacial foreshortening, and disrupted hindbrain segmentation.
      Ethanol exposure enhanced cell death within areas populated by cranial neural
      crest cells, particularly in the hindbrain and craniofacial mesenchyme. In
      contrast, control embryos had limited cell death within these regions. Subsequent
      immunolabeling with neural crest cell-specific antibody revealed that ethanol
      treatment resulted in fewer neural crest cell numbers, whereas neural crest
      migration patterns were unaffected by ethanol. These results suggest that
      prenatal ethanol exposure leads to loss of cranial neural crest cells. Such a
      loss could result, in part, in the phenotype characteristic of FAS.

PMID- 7625574
TI  - Ethanol consumption reduces the cytolytic activity of lymphokine-activated killer
      cells.
AB  - Ethanol (20% w/v) given to female C57BL/6 mice in their drinking water reduces
      splenic natural killer (NK) cell cytolytic activity after 2, 4, and 10 weeks of
      consumption. This reduction is transient because the levels of NK cell
      cytotoxicity from ethanol-consuming mice are nearly equal to those of water
      drinking mice after splenocytes were incubated in 1000 IU/ml of recombinant
      interleukin-2 (rIL2) for 16-18 hr. In this study, mice were given 20% w/v ethanol
      in the drinking water for 2 weeks. Splenic NK cells were enriched up to 88% by
      negative selection based on surface expression of NK1.1. Enriched NK cells were
      expanded in rIL2 for 6 days. Lymphokine-activated killer (LAK) cells from both
      ethanol-consuming and water-drinking mice were > 95% NK1.1+. LAK cell cytolytic
      activity was significantly lower against NK-insensitive P815 mastocytoma [6.67 +/
      2.18 vs. 17.21 +/- 1.8 lytic units (LUs), p < 0.01], moderately NK-sensitive B16
      melanoma (25.3 +/- 6.6 vs. 66.2 +/- 14.2 LU, p < 0.05), and NK-sensitive YAC-1
      lymphoma targets (80.5 +/- 34.7 vs. 177.0 +/- 43.6 LU, p < 0.005) in cells from
      ethanol-consuming mice compared with water-drinking controls. Ethanol consumption
      did not affect the morphology or phenotype of LAK cells with respect to surface
      expression of NK1.1, B220, CD3, CD25, CD11a, CD54, CD45RB, or class I major
      histocompatibility complex.

PMID- 7625575
TI  - Neuroactive steroid sensitivity in withdrawal seizure-prone and -resistant mice.
AB  - Withdrawal Seizure-Prone (WSP) and -Resistant (WSR) mice, which were selectively
      bred for severe (WSP) or mild (WSR) handling-induced convulsions (HICs) following
      chronic ethanol inhalation, were found to differ in sensitivity to the
      anticonvulsant effects of the neuroactive steroid 3 alpha-hydroxy-5 alpha-pregnan
      20-one (3 alpha,5 alpha-P. 3 alpha,5 alpha-P (5 or 10 mg/kg, ip) significantly
      increased seizure thresholds to pentylenetetrazol in ethanol-native males of both
      the WSP and WSR lines. In general, WSP mice were more sensitive than WSR mice to
      the anticonvulsant effect of 3 alpha,5 alpha-P. Subsequent studies in male WSP
      mice exposed to ethanol vapor or air for 24 hr demonstrated enhanced sensitivity
      to the anticonvulsant effect of 3 alpha,5 alpha-P (0.5-20 mg/kg, ip) during
      ethanol withdrawal. Only the highest dose affected HICs in air-exposed animals,
      whereas both the two highest doses significantly reduced HICs in ethanol-exposed
      mice. These results provide the first demonstration that 3 alpha,5 alpha-P
      attenuates ethanol withdrawal convulsions and indicate enhanced sensitivity to
      the anticonvulsant effect of 3 alpha,5 alpha-P in animals withdrawing from
      ethanol dependence.

PMID- 7625576
TI  - Staurosporine, a protein kinase inhibitor, increases the intoxicating potencies
      of ethanol and other n-alkanols in Rana pipiens tadpoles.
AB  - Central nervous system protein kinases are the intracellular effectors for many
      of the signal transduction pathways essential to neurotransmission. Although the
      in vitro activity of at least one of these important enzymes, protein kinase C,
      is diminished by therapeutic concentrations of ethanol and other central
      depressants, the relationship of this effect to intoxication in vivo is not
      known. If intoxication by ethanol involves central protein kinase inhibition,
      then other inhibitors of these enzymes should enhance ethanol's intoxicating
      potency. To test this hypothesis, we compared the median effective concentrations
      of ethanol and two other n-alkanols for loss-of-righting reflex in Rana pipiens
      tadpoles pretreated with staurosporine and in untreated controls. Alkanol
      concentrations were confirmed by gas chromatography and staurosporine
      concentrations by ultraviolet absorbance spectrophotometry. Results obtained with
      650 animals demonstrate that pretreatment with staurosporine concentrations in
      the nanomolar range significantly decrease the median effective concentration for
      ethanol (56% of control; p < 0.001), butanol (38% of control; p < 0.001), and
      octanol (59% of control; p < 0.001). This finding supports that central protein
      kinase inhibition may be involved in the acute intoxicating effects of ethanol
      and other n-alkanols.

PMID- 7625577
TI  - Polymorphism of a class 3 aldehyde dehydrogenase present in human saliva and in
      hair roots.
AB  - The types of aldehyde dehydrogenases (ALDH) present in human hair roots and in
      saliva were investigated. ALDH was detected by activity staining following
      separation of crude extracts by isoelectric focusing. Hair roots were found to
      express ALDH1, ALDH2, ALDH3, and ALDH4, whereas saliva expressed ALDH3. Two
      different patterns of ALDH3 were detected in hair roots collected from 42 donors,
      40 expressed one pattern (variant I) and two another pattern (variant II) of
      activity staining. The variant I pattern of hair root ALDH3 changed with
      repetitive freezing and thawing of the sample, whereas the variant II pattern was
      stable. In contrast to hair root ALDH3, all patterns of ALDH3 activity in saliva
      were stable. The patterns of ALDH3 activity present in human hair roots that had
      been frozen and thawed twice matched those present in saliva collected from the
      same individual. Three polymorphisms of ALDH3 (variants I, II, and III) were
      detected in the 33 saliva samples analyzed. Variants I and II were inherited in
      each of three generations of a 10-member family.

PMID- 7625578
TI  - Loss of reproductive competence at an earlier age in female rats exposed
      prenatally to ethanol.
AB  - Previous studies have shown that prenatal ethanol exposure can partially
      masculinize or defeminize neurobehavioral development of female rats. An early
      age of onset of anovulation is one of the primary characteristics of partial
      defeminization. Consequently, we examined the occurrence of anovulation in fetal
      alcohol-exposed (FAE) female rats at 2, 6, and 12 months of age using both
      vaginal cytology as well as wheel-running behavior. We assessed the ability of
      estrogen and progesterone to elicit proprioceptive behaviors and lordosis at 2
      and 17 months of age. Female subjects were derived from Sprague-Dawley dams
      administered an ethanol liquid diet (35% ethanol-derived calories), a pair-fed
      isocaloric liquid diet, or fed lab chow from days 14 to 22 of gestation. Litter
      representatives were placed in a computer-monitored wheel-running apparatus under
      a 12-hr lighting schedule from 49 to 60 days of age. Vaginal smears were taken
      from littermates during this same period. This same procedure was conducted again
      from 180 to 196 and from 380 to 396 days of age, except that vaginal cytology was
      examined in the same animals immediately after wheel-running behavior was
      studied. At approximately 2 months of age, a normal cyclical pattern of wheel
      running, characteristic of 4- to 5-day estrus cycles, was observed in all
      animals. No differences were detected in mean activity levels during the wheel
      running period. This was accompanied by normal cyclic vaginal cytology and normal
      proprioceptive behaviors and lordosis. At 6 months of age, FAE females exhibited
      significantly reduced wheel-running.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7625579
TI  - Mechanisms of acetaldehyde-mediated growth inhibition: delayed cell cycle
      progression and induction of apoptosis.
AB  - Chronic ethanol exposure has been associated with pleiotropic effects on cellular
      function in vivo and in vitro, including inhibition of growth. To date, it has
      been difficult to dissociate the primary effects of ethanol from the effects of
      ethanol metabolism, generation of acetaldehyde, and reducing equivalents. We have
      previously described the development of a Chinese hamster ovary cell line, A-10,
      which expresses a transfected murine-liver alcohol dehydrogenase. Cultures of
      these cells accumulate acetaldehyde due to the low level of aldehyde
      dehydrogenase. One noticeable effect of chronic acetaldehyde exposure, but not
      ethanol exposure, is the inhibition of cell growth. This study focuses on the
      mechanisms that underlie this growth inhibition. Our studies with the A-10 cell
      on the rates of [3H]thymidine incorporation and flow cytometry of asynchronous
      cultures indicated that acetaldehyde did not lead to arrest of the cell cycle in
      the G1 phase as has been found in other models of ethanol exposure. Rather, we
      observed a generalized delay in cell cycle progression. However, the slower cell
      cycle did not account exclusively for the slower rates of cell accumulation.
      Chronic exposure to acetaldehyde also increased the rate of cell death. The
      increased rate of cell death was both cumulative and dose-dependent. The dead
      cells accumulated in the medium and were apoptotic. Apoptosis was confirmed using
      morphological criteria and quantitation of DNA fragmentation. These data lend
      additional support to the idea that chronic acetaldehyde exposure can affect the
      mechanisms that regulate cell division and the apoptotic program.

PMID- 7625580
TI  - Rat mitochondrial aldehyde dehydrogenase polymorphism and major
      histocompatibility complex RT1.A phenotypes are not associated with alcohol
      drinking in P and NP rats.
AB  - Previous studies revealed polymorphisms in mitochondrial aldehyde dehydrogenase
      (ALDH2) and the major histocompatibility complex RT1.A that appeared in
      association with alcohol drinking preference in the alcohol-preferring (P) and
      alcohol-nonpreferring (NP) rat lines. To determine the strength of these
      associations, the P and NP lines were crossed, and cosegregation studies were
      performed in the F2 progeny. The ALDH2Q allele and the ALDH2R allele, found in
      the P and NP lines, respectively, were found not to be associated with the high
      and low drinking animals in the F2 progeny. Kinetic studies with ALDH2Q and
      ALDH2R isozymes purified from the mitochondria of P and NP rat livers,
      respectively, showed that the polymorphism would not be expected to be associated
      with altered aldehyde metabolism. The association between RT1.A and alcohol
      preference (RT1.Auu with high and RT1.AII with low alcohol intake) also could not
      be confirmed in the segregating F2 progeny of the P x NP intercross.

PMID- 7625582
TI  - Carbohydrate-deficient transferrin--a valid marker of alcoholism in population
      studies? Results from the Copenhagen City Heart Study.
AB  - Carbohydrate-deficient transferrin (CDT) was analyzed by a modified
      radioimmunoassay test in a random population sample of 400 individuals, and
      results were compared with reported alcohol intake derived from a structured
      questionnaire. Among the 180 men, the test was found to be acceptable with
      respect to detecting harmful alcohol intake (> 35 beverages/week) and alcohol
      intake above the recommended level (21 beverages/week), although the positive
      predictive values were low. Among the 220 women, the test was invalid with low
      predictive values. CDT was compared with other known markers of high alcohol
      intake, and it was observed that CDT had higher sensitivity and specificity than
      AST and short Michigan Alcoholism Screening Test (sMAST) in men, whereas the
      positive and negative predictive values were low in all tests. A combination of
      CDT and AST proved to be a better marker of both harmful alcohol intake and
      alcohol intake above the recommended level than the other markers. Neither CDT,
      AST, CDT/AST, nor sMAST proved to be useful as markers of alcohol intake in
      women. There were no differences between the values for pre- and postmenopausal
      women. These results from a population survey indicate that CDT is a marker of
      alcohol intake among men, although not ideal, but CDT cannot be used in the
      screening of harmful alcohol intake in women.

PMID- 7625581
TI  - Increases and time-course variations in beta-hexosaminidase isoenzyme B and
      carbohydrate-deficient transferrin in serum from alcoholics are similar.
AB  - beta-Hexosaminidase B-isoforms (beta-hexosaminidase B, P, and intermediate forms;
      abbreviated herein as "Hex B") and serum carbohydrate-deficient transferrin (CDT)
      are two markers of alcohol abuse. In the present study, we have compared "Hex B"
      with CDT as markers of alcohol abuse in a group of alcoholics hospitalized for
      detoxification after a period of heavy alcohol abuse. We have also followed the
      disappearance rate of these two markers from circulation. "Hex B" was elevated in
      38 of 42 patients hospitalized for detoxication, whereas CDT was elevated in 35
      of 42 patients. A highly significant correlation was noted between "Hex B" and
      CDT in these patients (p = 0.52, p < 0.001). Neither "Hex B" nor CDT correlated
      with gamma-glutamyltransferase or AST. The disappearance rates from serum of "Hex
      B" and CDT were determined in 21 hospitalized patients followed for up to 15
      days. "Hex B" and CDT showed similar time-course variation and half-lives, 6.5 +/
      3.7 (mean +/- SD) and 8.6 +/- 4.1 days, respectively. The possible reasons for a
      relation between these two markers are discussed, and it is concluded that more
      experience of both "Hex B" and CDT in unselected populations is needed to
      establish the diagnostic potential of these tests as markers of alcohol abuse.

PMID- 7625583
TI  - A double-blind, placebo-controlled study of nortriptyline and bromocriptine in
      male alcoholics subtyped by comorbid psychiatric disorders.
AB  - This double-blind, placebo-controlled, 6-month follow-up treatment study
      investigated the efficacy of bromocriptine and nortriptyline in attenuating
      drinking behavior and psychiatric symptoms in 216 male alcoholic patients
      subtyped by comorbid psychiatric disorder(s). Three well-defined subtypes were
      examined: alcoholism only, alcoholism + affective/anxiety disorder, and
      alcoholism + antisocial personality disorder. It was hypothesized that both
      medications would relieve negative affective symptoms associated with alcohol use
      and would be particularly effective for the affective/anxiety subgroup. Contrary
      to our predictions, the only significant effects found were with the antisocial
      personality disorder patients who were receiving nortriptyline. One
      interpretation of the results was that nortriptyline may have reduced impulsive
      drinking in the antisocial personality disorder subgroup by actions on
      serotonergic neurotransmission.

PMID- 7625584
TI  - Auditory P300 in young alcoholics: regional response characteristics.
AB  - An auditory oddball paradigm was used to record the P300 component of the event
      related potential (ERP) in a group of medication-free, chronic male alcoholics (n
      = 51, mean = 32.2) and a control group (n = 25, mean = 27.2). Each subject
      received a binaurally presented series of high (1600-Hz)- and low (600-Hz)
      frequency tones. The designation of the rare tone (0.125 probability) was
      alternated across subjects. When the subject detected the rare tone, he made a
      button press as quickly as possible to record his reaction time. Scalp recordings
      using the entire 10/20 System, as well as interpolated placements, were made from
      31 electrodes. For purposes of statistical analyses, five regional electrode
      groups were created: F (frontal), C (central), P (parietal), O (occipital), and T
      (temporal). The results of MANOVA indicated that control P300 amplitudes were
      significantly greater than those of the alcoholics in all five regions, whereas
      there were no P300 latency differences between groups in any region. Regional
      response differences between the groups were also compared with measures of
      surface energy (SE) (Wang et al., 1994). SE is a recently developed, reference
      free global field measure that uses the entire scalp potential field and treats
      potentials at different positions differently. SE was significantly reduced in
      the alcoholics compared with the controls in both the C (p < 0.0003) and P (p <
      0.0006) regions, although there were no differences in its distribution.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7625585
TI  - Relationship between alcohol-related expectancies and anterior brain functioning
      in young men at risk for developing alcoholism.
AB  - This experiment examined the relationship between anterior brain functioning and
      alcohol-related expectancies. Ninety-one young men at risk for developing
      alcoholism were assessed on the Alcohol Expectancy Questionnaire (AEQ) and
      administered neuropsychological and EEG tests. Three of the scales on the AEQ,
      including the "Enhanced Sexual Functioning" scale, the "Increased Social
      Assertiveness" scale, and items from the "Global/Positive Change scale," were
      used, because each of these scales has been found to discriminate alcohol-based
      expectancies adequately by at least two separate sets of investigators.
      Regression analysis found that anterior neuropsychological tests (including the
      Wisconsin Card Sorting test, the Porteus Maze test, the Controlled Oral Word
      Fluency test, and the Luria-Nebraska motor functioning tests) were predictive of
      the AEQ scale scores on regression analysis. One of the AEQ scales, "Enhanced
      Sexual Functioning," was also predicted by WAIS-R-Verbal scales, whereas the
      "Global/Positive" AEQ scale was predicted by the WAIS-R Performance scales.
      Regression analysis using EEG power as predictors found that left versus right
      hemisphere "difference" scores obtained from frontal EEG leads were predictive of
      the three AEQ scales. Conversely, parietal EEG power did not significantly
      predict any of the expectancy scales. It is concluded that anterior brain any of
      the expectancy scales. It is concluded that anterior brain functioning is
      associated with alcohol-related expectancies. These findings suggest that alcohol
      related expectancy may be, in part, biologically determined by frontal/prefrontal
      systems, and that dysfunctioning in these systems may serve as a risk factor for
      the development of alcohol-related behaviors.

PMID- 7625586
TI  - Autonomic reactivity and alcohol-induced dampening in men at risk for alcoholism
      and men at risk for hypertension.
AB  - Both sons of male alcoholics with multigenerational family history of male
      alcoholism (MFH) and sons of essential hypertensives (HTs) exhibit elevated
      psychophysiological reactivity to stress when compared with male controls (FH-).
      MFHs also demonstrate a significant baseline heart rate increase and stress
      response dampening following alcohol consumption. The present study investigates
      the specificity of this alcohol-induced psychophysiological response pattern by
      testing these two risk groups in a shock response paradigm, both sober and
      alcohol-intoxicated. A repeated measures analysis of variance on sober and
      alcohol-intoxicated heart rate reactivity yielded a significant risk by alcohol
      interaction, indicating that alcohol consumption led to a greater decrease in
      reactivity in the MFH group compared with the HT and FH- groups. Similar results
      were obtained for muscle tension measures. MFHs also displayed greater increases
      in resting baseline heart rate and muscle tension when alcohol intoxicated. The
      results may reflect a sensitivity to negatively and positively reinforcing
      effects of alcohol specific to individuals with multigenerational familial
      histories of alcoholism.

PMID- 7625587
TI  - Antagonism of ethanol by pretreatment or posttreatment with RO 15-4513 and
      indomethacin alone or in combination.
AB  - RO 15-4513, an inverse agonist at the GABA/benzodiazepine receptor Cl- channel
      complex, antagonizes multiple effects of ethanol. Prostaglandin synthesis
      inhibitors, such as indomethacin, also antagonize several effects of alcohols.
      However, prostaglandin synthesis inhibitors and RO 15-4513 each provide only
      partial antagonism of ethanol, typically seen as a dose-related effect with a
      maximum efficacy of approximately 50%. The purpose of this study was to: (1)
      compare the relative efficacy of these compounds for antagonizing ethanol; (2)
      compare the effectiveness of preethanol treatment versus postethanol treatment
      with each drug; and (3) compare the effect of RO 15-4513 and indomethacin in
      combination with the effects of each drug alone. The results show that
      indomethacin significantly decreased duration of loss of the righting reflex when
      administered either pre- or postethanol. Conversely, RO 15-4513 decreased
      duration of loss of the righting reflex only when given preethanol. When
      coadministered, RO 15-4513 and indomethacin did not show additive or synergistic
      effects. Compounds from these two drugs classes should continue to prove useful
      in elucidating ethanol's mechanisms of action.

PMID- 7625589
TI  - Pathways into risk: temperament and behavior problems in three- to five-year-old
      sons of alcoholics.
AB  - Evidence suggests that a child with a difficult temperament, reared in an
      alcoholic family, is at high risk for the development of behavior problems that
      antedate the emergence of antisocial behavior, alcoholism, and coactive
      psychopathology. However, the causal linkage between difficult temperament and
      problem behavior in childhood, and antisociality and alcohol abuse in adulthood
      is far from certain, in part because few studies assess emergent behavior
      patterns in young children of alcoholics. In this study, we investigated the
      temperament-behavior problem relationship in 191 3- to 5-year-old boys, 149 of
      whom were being reared in high-risk alcoholic, low socioeconomic environments.
      Boys were classified as high in problem behavior or not based on standardized
      clinical cut-off scores for Total Behavior Problems from the Child Behavior
      Checklist. Results indicated that boys rated in the clinical range for total
      behavior problems exhibited more characteristics of difficult temperament than
      boys who were not rated in the clinical range. Parents of the boys in the
      clinical group had significantly more alcohol-related problems, higher levels of
      antisociality, and significantly lower levels of socioeconomic status, income,
      and education. Results are consistent with the supposition that the difficult
      temperament-behavior problem relationship flourishes in the context of an
      antisocial, alcoholic family environment.

PMID- 7625588
TI  - Patterns of cognitive impairment among alcoholics: are there subtypes?
AB  - The mild generalized dysfunction hypothesis of alcohol abuse's deleterious
      effects on cognitive processes has gained support from a number of studies in
      which detoxified alcoholics have a lower mean performance level than peer
      controls on a variety of neuropsychological tests. This approach might obscure
      consistent but different patterns of preserved and impaired cognitive performance
      among subgroups of alcoholics, suggestive of alternative hypotheses. To test this
      possibility, neuropsychological test data from two large, independent samples of
      alcoholics (sample 1, n = 143; sample 2, n = 130) and controls (sample 1, n = 97;
      sample 2, n = 83) were subjected to separate centroid hierarchical cluster
      analyses. For both samples, the majority of alcoholics (94% and 94%) exhibited a
      pattern of impaired verbal and nonverbal performance and deficits in memory and
      perceptual motor skill, with normal motor skill. The alcoholics who did not fit
      this pattern showed more severe or wide-ranging impairments. These findings
      indicate that empirical support for the mild generalized dysfunction hypothesis
      of alcoholics' cognitive deficits is not an artifact of averaging.

PMID- 7625590
TI  - Regional brain metabolic response to lorazepam in subjects at risk for
      alcoholism.
AB  - The mechanisms underlying the blunted response to alcohol administration observed
      in subjects at risk for alcoholism are poorly understood and may involve GABA
      benzodiazepine receptors. The purpose of this study was to investigate if
      subjects at risk for alcoholism had abnormalities in brain GABA-benzodiazepine
      receptor function. This study measured the effects of 30 micrograms/kg (i.v.) of
      lorazepam, on regional brain glucose metabolism using positron emission
      tomography and 2-deoxy-2[18F]fluoro-D-glucose in subjects with a positive family
      history for alcoholism (FP) (n = 12) and compared their response with that of
      subjects with a negative family history for alcoholism (FN) (n = 21). At
      baseline, FP subjects showed lower cerebellar metabolism than FN. Lorazepam
      decreased whole-brain glucose metabolism, and FP subjects showed a similar
      response to FN in cortical and subcortical regions, but FP showed a blunted
      response in cerebellum. Lorazepam-induced changes in cerebellar metabolism
      correlated with its motor effects. The decreased cerebellar baseline metabolism
      in FP as well as the blunted cerebellar response to lorazepam challenge may
      reflect disrupted activity of benzodiazepine-GABA receptors in cerebellum. These
      changes could account for the decreased sensitivity to the motor effects of
      alcohol and benzodiazepines in FP subjects.

PMID- 7625593
TI  - Depression of an inhibitory reflex, the masseteric silent period, in recovering
      alcoholics.
AB  - Because inhibitory deficits may contribute to motor incoordination of alcoholics,
      we proposed that the duration of the masseteric silent period (SP), an inhibitory
      reflex, might be shorter in alcoholics (ALs) than in nonalcoholics (NAs). To test
      this hypothesis, we measured the SP in a racially mixed group of 12 ALs and 12
      NAs matched for age (31-49 years) and sex. All subjects were normotensive, had
      full dentition, and reported no major medical problems. Sensory and motor
      conduction velocities of the anterior tibialis, ulnar, and medial nerves were
      measured for each subject, and were not different in ALs and NAs. Jaw jerk and SP
      were evoked by tapping the chin manually with a rubber hammer containing a
      circuit to trigger the oscilloscope display of the masseter EMGs. Averaged mean
      latencies and durations of the SPs were not significantly different between the
      right and left masseters. SP latencies were significantly (0.7 msec) shorter in
      ALs than NAs (p < 0.01). The mean SP duration for ALs (13.9 +/- 1.6 msec) was
      also significantly shorter than that of the NAs (24.4 +/- 2.4 msec; p < 0.001).
      Results support the hypothesis that chronic alcoholism may interfere with
      inhibitory mechanisms in the CNS.

PMID- 7625592
TI  - Thiamine phosphatases in human brain: regional alterations in patients with
      alcoholic cirrhosis.
AB  - Activities of thiamine monophosphatase (TMPase) and thiamine diphosphatase
      (TDPase) were measured in homogenates of brain tissue obtained at autopsy from
      eight alcoholic cirrhotic patients who died in hepatic coma and nine controls
      matched for age and for postmortem delay interval and free from neurological or
      psychiatric disorders, hepatic disease, or other conditions of grossly impaired
      nutritional status. Enzyme activities were measured by standard
      spectrophotometric techniques. Both TMPase and TDPase were distributed unevenly
      in brain with highest activities being recorded in temporal cortex. Regional
      correlations between TMPase and TDPase, however, were poor. TDPase activities in
      brain tissue from alcoholic cirrhotic patients were significantly increased in 5
      of 6 brain regions, by 26 to 153% (p < 0.05). TMPase activities in alcoholic
      cirrhotics, on the other hand, were unchanged in all brain regions, with the
      exception of caudate nucleus where they were increased by 70% (p < 0.05). These
      findings add to the substantial body of evidence suggesting that alcoholic liver
      disease is associated with abnormal thiamine status and with altered thiamine
      neurochemistry. Increased TDP degradation resulting from increased activities of
      TDPase could contribute to the pathophysiological mechanisms involved in alcohol
      related brain dysfunction.

PMID- 7625594
TI  - Voice of the victims.
AB  - Over the past 10 years, I have been privileged to conduct educational forums for
      audiences containing many recovering alcoholics or otherwise chemically dependent
      persons. In these forums about the addictive diseases and their treatment and
      research possibilities, significant interaction with the audience members occurs.
      During these interactions, certain anecdotal phenomena seem to predominate. The
      repetitive nature of these reports suggests the need for systematic
      investigation. As with editorial comments in major medical journals, observed
      phenomena and unanswered questions from the victims can be valuable in the
      generation of testable hypotheses. Perhaps the ideas presented herein will be
      useful in the development of future research on alcohol abuse and alcoholism.

PMID- 7625591
TI  - Evaluation of the effect of alcohol consumption on erythrocyte lipids and
      vitamins in a healthy population.
AB  - There is epidemiological evidence that a moderate consumption of alcohol could
      reduce coronary heart disease. To corroborate this statement and to see how the
      consumption of red wine affects phospholipid and fatty acid patterns and
      antioxidant status, a survey was conducted on 58 adult males (20-75 years old). A
      questionnaire was used to discover their medical history, various constitutional
      and life-style factors, food habits, and nutrient intake; and the type and amount
      of alcoholic intake were investigated by means of a questionnaire. Subjects were
      divided into two groups of nondrinkers and average drinkers (mean 46.5 +/- 4.4,
      range 30.2-63.4 g/day), and the effect of alcohol was made on the following
      variables: gamma-glutamyltranspeptidase, apolipoprotein AI, apolipoprotein B,
      total and high-density lipoprotein-cholesterol, triglycerides, and antioxidant
      vitamins were determined in plasma; and phospholipids the fatty acids of
      phosphatidylcholine (PC) and phosphatidylethanolamine total cholesterol, alpha
      tocopherol, beta-carotene, and retinol were determined in red blood cells (RBCs).
      There were no significant differences between the two groups in protein, fat,
      carbohydrate, retinol equivalent, alpha-tocopherol content, and
      cholesterol/saturated fat index of their diet. Analysis of the plasma levels of
      biochemical variables--adjusted for age, smoking (number of cigarettes/day), and
      body mass index--showed a significant increase of gamma-glutamyltranspeptidase
      and apolipoprotein AI concentration in the average drinkers compared with
      nondrinkers. Plasma alpha-tocopherol and retinol levels were also significantly
      higher in average drinkers. In the latter group, ANCOVA demonstrated a lower
      percentage of sphingomyelin in RBCs, with a lower sphingomyelin/PC
      ratio.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7625596
TI  - [Brainstem evoked potentials in diagnosis of infantile hypoacusis].
AB  - This paper deals with the auditory brainstem responses and its clinical
      application to the assessment of hearing losses, degree of severity and
      topographic diagnosis, in children.

PMID- 7625597
TI  - [Involvement of the facial nerve in tumors of the neck and face. Report of 17
      cases].
AB  - Seventh nerve involvement for tumors of the neck of the face is an event not too
      much infrequent. The paralysis can present due to direct propagation or for not
      close vicinity. Seventeen (17) patients with facial palsies in association with
      neoplasties seen in a four years term (1989 - 1992) are contemplated. This figure
      represents a 6.6 percent of the whole number studied (N. = 270). The paper deals
      with clinical, etio-pathogenic features and especially with the so-called "alarm
      signals".

PMID- 7625595
TI  - [Tonsillectomies and adenoidectomies with less than six hour admittance].
AB  - Surgery practice, as day cases, is as old as surgery itself, but actually because
      of the assembly of present-day circumstances, specially the shortage of ward
      beds, make necessary to gain advantage of resources available. The new requests
      for medical attendance as well the technological novelties have influenced at
      Hospital de Cruces to establish the Outpatients Surgical Unit. A good
      organisation allows the Adeno-tonsillectomy surgery with little risk in these
      Unities. We describe our experience, the advantages and the complications of this
      behavior.

PMID- 7625598
TI  - [Middle ear pressure changes following adenoidectomy. Contribution to the
      etiopathogenic study of serous otitis media].
AB  - This paper deals in the pursuit done on endotympanic pressures in children
      operated upon adenoidectomy, a lot of them simultaneously suffering from serious
      otitis media. The obtained results are compared with those of healthy children,
      with the aim of set up the pressure changes within the middle ear due to surgery
      and as well the knowledge of the natural evolvement of the serious otitis. In
      accordance with date registered and the perusal of the Bibliography at hand, the
      AA. try to find out the possible influence of the adenoid hypertrophy on this
      type of otitis. But all without arguing the role played by other causes (split
      palate, neoplastic obstruction, ciliar dyskinesy, etc.). Finally a new etio
      pathogenic mechanism, in order to explain the negative pressures inside the
      middle ear due to adenoid hyperplasty, is proposed.

PMID- 7625599
TI  - [Laryngeal metastasis of a gastric adenocarcinoma].
AB  - A 63-year-old patient with metastasic tumour of the larynx (epiglottis) and neck
      from an asymptomatic stomachal adenocarcinoma is presented.

PMID- 7625600
TI  - [Treatment and outcome of infantile cholesteatoma surgery].
AB  - Infantile Cholesteatoma has been lately the aim of a large number of papers
      dealing with its natural history and optimal treatment. The outcome of 26 cases
      of ear surgery, done between 1990 and 1991, are reviewed. The etiology of
      Cholesteatoma was congenital in 2 cases, iatrogenic in an other one and unknown
      for the remainder (88%). Fifteen (15) closed surgical procedures and 11 open were
      carry out, achieving global removal of lesions in 76 percent of cases. Ninety-one
      (91%) of open tympanoplasties and 66 percent of closed procedures. Six cases
      evolved to recidivation (and later reoperatively reconverted in open cases) owing
      either to the erosion of the ossicular chain or encroachment of the recessus.
      Reconstructions of the ossicular chain was undertaken in 61.5 percent of cases
      and the hearing preserved in all instances and improved in 35 percent of
      reconstructions.

PMID- 7625601
TI  - [Adenosquamous carcinoma of minor salivary glands. Reporting a case in the
      tongue].
AB  - Adenosquamous carcinoma of the salivary glands is an unusual neoplasm not
      unanimously included in many classifications of salivary gland malignancies. A
      case sited in the oral cavity, within the tongue is reported. Clinical and
      histopathologic features are described together with a discussion about treatment
      and behaviour. We also include an updated of literature relating to this entity.

PMID- 7625602
TI  - Immunocytochemical identification of serotonergic supraependymal nerve fibers in
      the third ventricle of the house musk shrew, Suncus murinus.
AB  - Supraependymal fibers of the house musk shrew (Suncus murinus) were examined by
      conventional scanning electron microscopy (SEM), backscattered electron (BSE)
      imaging of enzyme immunohistochemistry and by immunotransmission electron
      microscopy in the dorsal part of the third ventricular wall. In this region,
      ependymal cells were not so heavily ciliated and conventional SEM studies showed
      two main categories of supraependymal fibers. The first type consisted of long
      fibers fasciculated which were distributed over the ventricular surface between
      the anterior commissure and the subfornical organ. The second category was a thin
      fiber which was observed on the ependymal luminal surface. Some of these fibers
      had varicoses or terminal-like swellings. This type of supraependymal fiber
      seemed to originate in the first type of fiber bundles. To confirm the nature and
      the distribution of serotonin-immunoreactive supraependymal fibers, BSE imaging
      using immunohistochemical reactions was used. Serotonin-immunoreactive structures
      were shown as highlighted structures by means of a backscattered electron mode.
      These investigations revealed that the majority of both types of supraependymal
      fibers observed by conventional SEM contained serotonin. A moderate number of
      serotonergic supraependymal fibers was observed on the ventricular surface of the
      subfornical organ. Immunohistochemical studies using Vibratome sections of
      identical ventricular regions revealed the presence of serotonin-immunoreactive
      processes, with the use of light- and electron-microscopy. They were distributed
      in in the third ventricle just adjacent to the ependymal luminal surfaces. These
      fibers contained immunoreactive large cored vesicles and immunonegative small
      clear vesicles.

PMID- 7625603
TI  - [Normal variation of arterial liver supply in mesenterico-celiacography].
AB  - Progress in operative techniques in surgery of the upper abdomen necessitates
      extensive preoperative diagnostic studies. Mesenterico-coeliacography along with
      CAT-SCAN form the basis for effective operative planning. In the angiography, the
      clinician is often confronted by variations in the arterial supply of the liver.
      These variations of the norm which are scarcely mentioned in anatomical textbooks
      must be carefully taken into consideration by the surgeon. In order to clarify
      the operative significance of these variations, we have conducted a retrospective
      study of the angiographies of the truncus coeliacus as well as of the arteria
      mesenterica superior. We found variations in 25.5% of 204 angiographies. The
      incidence of deviant and accessory hepatic arteries was 33.8% and of variations
      in the truncus coeliacus was 6.7%. These variations of the norm are discussed as
      to clinical and embryological aspects.

PMID- 7625604
TI  - The cranial venous system in the rat: anatomical pattern and ontogenetic
      development. II. Dorsal drainage.
AB  - The precise anatomical pattern and the developmental sequences of the dorsal
      cranial sinuses are described with special reference to the petrosquamosal sinus.
      The pattern of the dorsal cranial venous system of the rat is quite similar to
      that of man, although there are certain important differences. In rats, the
      transverse sinus bifurcates into the small dorsally directed sigmoid sinus and
      the large laterally directed petrosquamosal sinus. The latter emerges through the
      wide petrosquamosal fissure and joins the maxillary and posterior facial veins,
      sending two roots to each. The superior sagittal sinus anastomoses ventrally with
      the interperioptic sinus. This pattern is already established at an early
      developmental stage and is obvious by gestational day E 19. The anlages of the
      transverse and the sigmoid sinuses are formed from anastomoses between the three
      dural stems which drain the blood from the brain vesicles via the primary head
      vein into the anterior cardinal veins. The middle dural stem is connected by a
      rich capillary network to both the developing maxillary vein and the external
      jugular venous system before day E 16, thus establishing the anlage of the
      petrosquamosal sinus. Its definitive pattern is already discernible on day E 18.
      The external jugular vein becomes the main cranial venous outflow in the
      postnatal rat.

PMID- 7625605
TI  - [Intramural blood vessel system of the large intestine of domestic ruminants].
AB  - The vascular system of the large intestine of 15 cattle, 10 sheep and 5 goats has
      been examined by means of corrosion vascular casts, histology and electron
      microscopy. The results are as follows: The course and ramification of the
      intestinal vessels are identical in the caecum, colon and rectum. Furthermore, as
      expected, amongst the species studied no substantial differences in the vascular
      architecture of the large intestinal wall could be determined. The extramural
      vessels reach the wall of the intestine at the mesenteric margin. Their branches
      build arterial or venous networks in the tela subserosa, which then divide into
      branches in the direction of the antimesenteric region. The connections between
      the blood vessels of the tela subserosa and the tela submucosa as well as the
      branches to the muscular layers emerge from these networks. In the tela submucosa
      an arterial and venous system can be found. The obvious vascular arrangement in
      the submucosa is arranged not only parallel to the stratum circulare of the
      tunica muscularis but also along the prevailing direction of the lamina
      muscularis mucosae. From this arrangement both a deep and a superficial
      submucosal vascular plexus can be denominated. The recurrent branches for the
      circular muscle layer as well as the afferent and efferent vessels of the mucosa
      originate from submucosal arteries and veins. The arterioles of the tunica mucosa
      branch at the level of the basal crypts into a periglandular capillary system
      running close to the lumen into a subepithelial capillary system. Here the
      capillaries drain into venules which advance to the region of the intestinal
      glands and consequently drain into collecting veins in the submucosa. Capillaries
      of the subepithelial lamina propria mucosae are furnished with continuous or
      fenestrated endothelial linings as the morphological equivalent of the secretory
      or resorption processes, respectively. In the walls of the large intestine of the
      bovine, sheep and goat there are neither arterio-venous anastomoses nor
      hemodynamic regulatory structures such as sphincters or so-called throttle veins
      at the points of transition from capillaries to venules. These results are in
      accord with the findings in the small intestine of domestic ruminants (Hummel
      1980).

PMID- 7625606
TI  - Morphology of thyroid follicular cells from adult marmosets (Callithrix jacchus).
AB  - The existence of follicles with a "super flat" epithelium and the large number of
      primary and especially secondary lysosomes and lipofuscin granules in these cells
      are characteristic features of the thyroid gland of adult marmosets (Callithrix
      jacchus, new-world monkeys). It is supposed that these morphological findings are
      indications of a relatively low function and early ageing.

PMID- 7625607
TI  - The interstitial space of the thyroid gland of marmosets (Callithrix jacchus).
AB  - The interstitial space of the thyroid gland of adult marmosets contains, like the
      stroma of other organs, cells and intercellular substance (matrix), blood vessels
      (predominantly capillaries), lymph vessels and unmyelinated nerves. It is
      demarcated from the follicular epithelium, the capillaries and Schwann cells by a
      basal lamina (BL). The perifollicular BL shows thickenings of up to 3 microns
      over long distances or a multilayered arrangement. These thickened segments
      exhibit numerous epithelial processes and ridges; in other words, the contour of
      the basal cell membrane is very irregular in these areas. Indentations of
      capillaries into the epithelium are rarely observed. The endothelium is only
      slightly porous. Lymph capillaries occur in large numbers. They originate freely
      in the interstitial space, show gaps or unspecific contacts between the thin
      endothelial cells; a basal lamina is missing. Bundles of 10-nm thick filaments
      (anchor filaments) extend to the endothelial cells of the lymph capillaries. Thin
      and very long (up to 8 microns) plate-like processes surround the capillaries or
      run parallel to the outer contour of the follicles. They originate at the poles
      of oval, fibroblast-like cells. Since these cells are FXIII- and C3bi-positive,
      they can be considered as dendritic cells. They obviously play a role in the
      frequently-observed autoimmune diseases of this species. In addition, monocytes
      and all transitional forms including macrophages, fibrocytes and lymphocytes as
      well as numerous mast cells occur. In the region of the BL, integrins of the beta
      1-group (alpha 6) can be demonstrated immunohistologically in addition to the
      usual components (collagen type IV, laminin and heparan sulfate-proteoglycan). Of
      the fibrillar collagens type I does not occur, type III occurs only in small
      amounts, whereas types V and VI are observed in large amounts. The presented
      findings may serve as basis for more extensive experiments on these primates.

PMID- 7625609
TI  - [Mirror symmetrical and "left dominant" organization in the gastrula stage molted
      parabiotic larva of mountain salamander].
AB  - Gastrulae of Triturus alpestris were laterally fused (body axes in equal
      directions). The parabiotic larvae mostly showed an undivided body with tail, but
      exhibited two heads. Defects of organogenesis were frequently observed in the
      gut, and, to some fewer extent, in the heart. The gut mostly develops undivided,
      the heart in singular or (with transitions) as two organs. The number of organ
      inversions and partial inversions was high (table 1). In addition a
      transindividual organ-symmetry (mirror-image symmetry of the "pair situs") was
      abundant (table 3, fig. 6) and the gut and the habenular nuclei showed a strong
      dominance for that phenotype. The organ inversions were more abundant in the
      right organ or part of the organ. These right-left-differences were statistically
      significant referring to the inversion tendency of the heart and the habenular
      nuclei (table 2). This "left-dominance" observed in the organ Anlagen
      investigated is discussed in regard to results published previously.

PMID- 7625608
TI  - Microvasculature of the dorsal mucosa of human fetal tongue: a SEM study of
      corrosion casts.
AB  - The vasculature of the dorsal mucosa of the tongue was investigated in 18-21 week
      human fetuses by corrosion casting and scanning electron microscopy.
      Microvascular systems of the fungiform, foliate and circumvallate papillae,
      albeit less complex, showed similarity to those described in children, while the
      capillary networks of the filiform papillae were not yet fully developed, having
      either a knot-like or cone-like form instead of the corolla-like pattern typical
      of the postnatal period. Morphological features suggesting angiogenesis included
      both capillary outgrowths characteristic of vascular sprouting and tiny holes in
      the vascular walls regarded as evidence of intussusceptive capillary growth. The
      subpapillary vascular network supplying and draining the papillary vessels was
      composed of the more superficial capillary bed and the deeper plexus of larger
      arterioles and venules.

PMID- 7625611
TI  - Inhibition of hair growth by subcutaneous injection of a sympathetic neurotoxin,
      6-hydroxydopamine in neonatal mice.
AB  - The effects of a sympathetic neurotoxin, 6-hydroxydopamine (6-OHDA), on hair
      growth in neonatal mice were examined. Newborn mice were injected once
      subcutaneously in the mid-dorsal region with 6-OHDA (0.3 mg/g body weight) and
      bovine serum albumin (BSA) or with BSA only (controls) on day 0. By day 10,
      distinct areas of hairless skin were observed surrounding the sites treated with
      6-OHDA. The areas of hairless skin were smaller at 15 days of age and were
      covered with hair by 20 days of age. Control sites injected with BSA only were
      indistinguishable from the surrounding skin at all ages examined. Microscopic and
      morphometrical analyses of skin obtained from the neonatal mice at various ages
      showed that the hairless skin in 6-OHDA-treated mice was thinner than the skin of
      control animals. The thinning of the skin and delay in hair growth induced by 6
      OHDA treatment showed a significant difference from the skin of control animals
      injected with BSA only. Immunohistochemical experiments demonstrated that the
      administration of 6-OHDA had caused the complete depletion of tyrosine
      hydroxylase-immunoreactive fibers (sympathetic fibers) around blood vessels and
      piloerector muscles and in nerve bundles throughout the dermis and subcutaneous
      tissue. These findings indicate that the sympathetic neurons are associated with
      skin thickness and hair growth in neonatal mice.

PMID- 7625612
TI  - Formation of the pharyngeal arch arteries in the chick embryo. Observations of
      corrosion casts by scanning electron microscopy.
AB  - An investigation was made of the formation of the pharyngeal arch arteries (PAAs)
      in developing chick embryos that ranged from Hamburger-Hamilton stage (st) 12 to
      st44 and 1-day-old chicks after hatching. Corrosion casts of the vasculature were
      made by injecting resin and examined by scanning electron microscopy. The
      relationship between the PAAs and associated organs was then demonstrated by
      computer-aided reconstruction. The ventral aorta connected with the dorsal aorta
      through a loop in front of the foregut at st12. We named this loop the primitive
      aortic arch to distinguish it from the true first PAA. The second PAA was found
      to form at st14 and the third PAA at st15, while the true first PAA to connect
      the dorsal and ventral aortae was found at st16. The aortic regions anterior to
      the first PAA then fused. By st19, the first PAA had disappeared and the fourth
      PAA had appeared. The fifth and sixth PAA were observed as a capillary plexus at
      st20 and st21. The fifth PAA consisted of a bypass of the sixth PAA during st22
      to st25. The second PAA was observed to be very slender at st23 and to rupture by
      st25. At the same time, the proximal parts of the first and second PAAs and the
      ventral aorta changed into the primary external carotid artery (ECA) and gave off
      branches to the upper and lower jaws. Furthermore, the distal part of the second
      PAA remained to become the two branches of the dorsal aorta giving rise to the
      stapedial artery and the root of the secondary ECA.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7625610
TI  - Early stages of chick somite development.
AB  - We report on the formation and early differentiation of the somites in the avian
      embryo. The somites are derived from the avian embryo. The somites are derived
      from the mesoderm which, in the body (excluding the head), is subdivided into
      four compartments: the axial, paraxial, intermediate and lateral plate mesoderm.
      Somites develop from the paraxial mesoderm and constitute the segmental pattern
      of the body. They are formed in pairs by epithelialization, first at the cranial
      end of the paraxial mesoderm, proceeding caudally, while new mesenchyme cells
      enter the paraxial mesoderm as a consequence of gastrulation. After their
      formation, which depends upon cell-cell and cell-matrix interactions, the somites
      impose segmental pattern upon peripheral nerves and vascular primordia. The newly
      formed somite consists of an epithelial ball of columnar cells enveloping
      mesenchymal cells within a central cavity, the somitocoel. Each somite is
      surrounded by extracellular matrix material connecting the somite with adjacent
      structures. The competence to form skeletal muscle is a unique property of the
      somites and becomes realized during compartmentalization, under control of
      signals emanating from surrounding tissues. Compartmentalization is accompanied
      by altered patterns of expression of Pax genes within the somite. These are
      believed to be involved in the specification of somite cell lineages. Somites are
      also regionally specified, giving rise to particular skeletal structures at
      different axial levels. This axial specification appears to be reflected in Hox
      gene expression. MyoD is first expressed in the dorsomedial quadrant of the still
      epithelial somite whose cells are not yet definitely committed. During early
      maturation, the ventral wall of the somite undergoes an epithelio-mesenchymal
      transition forming the sclerotome. The sclerotome later becomes subdivided into
      rostral and caudal halves which are separated laterally by von Ebner's fissure.
      The lateral part of the caudal half of the sclerotome mainly forms the ribs,
      neural arches and pedicles of vertebrae, whereas within the lateral part of the
      rostral half the spinal nerve develops. The medially migrating sclerotomal cells
      form the peri-notochordal sheath, and later give rise to the vertebral bodies and
      intervertebral discs. The somitocoel cells also contribute to the sclerotome. The
      dorsal half of the somite remains epithelial and is referred to as the
      dermomyotome because it gives rise to the dermis of the back and the skeletal
      musculature. the cells located within the lateral half of the dermomyotome are
      the precursors of the muscles of the hypaxial domain of the body, whereas those
      in the medial half are precursors of the epaxial (back) muscles.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7625613
TI  - Somatostatin and leu-enkephalin in the rat auditory brainstem during fetal and
      postnatal development.
AB  - A transient expression of the neuropeptide somatostatin has been described in
      several brain areas during early ontogeny and several opioid peptides, such as
      leu-enkephalin, have also been found in the brain at this stage in development.
      It is therefore believed that somatostatin and leu-enkephalin may play a role in
      neural maturation. The aim of the present study was to describe the
      spatiotemporal pattern of somatostatin and leu-enkephalin immunoreactivity in the
      auditory brainstem nuclei of the developing rat and to correlate it with other
      developmental events. In order to achieve this goal, we applied peroxidase
      antiperoxidase immunocytochemistry to rat brains between embryonic day (E) 17 and
      adulthood. Somatostatin immunoreactivity (SIR) was found in all nuclei of the
      auditory brainstem, yet it was temporally restricted in most nuclei. SIR appeared
      prenatally and reached maximum levels around postnatal day (P) 7, when great
      numbers of immunoreactive neurons were present in the ventral cochlear nucleus
      (VCN) and in the lateral lemniscus. At that time relatively low numbers of cells
      were labeled in the dorsal cochlear nucleus, the lateral superior olive (LSO),
      and the inferior colliculus (IC). During the same period, when somata in the VCN
      were somatostatin-immunoreactive (SIR), a dense network of labeled fibers was
      also present in the LSO, the medial superior olive (MSO), and the medial nucleus
      of the trapezoid body (MNTB). As these nuclei receive direct input from VCN
      neurons, and as the distribution and morphology of the somatostatinergic fibers
      in the superior olivary complex (SOC) was like that of axons from VCN neurons,
      these findings suggest a transient somatostatinergic connection within the
      auditory system. Aside from the LSO, MSO, and MNTB, labeled fibers were found to
      a smaller extent in all other auditory brainstem nuclei. After P7, the SIR
      decreased and only a few immunoreactive elements were found in the adult auditory
      brainstem nuclei, indicating that somatostatin is transiently expressed in the
      rat auditory brainstem. Leu-enkephalin immunoreactivity showed a lower number and
      weaker intensity of labeled structures as compared to SIR, with E18 being the
      earliest day at which labeled fibers appeared in the SOC. At birth,
      immunoreactive fibers were also present in the cochlear nuclear complex and in
      the IC. Leu-enkephalin immunoreactive somata were found only after P12 in the CN
      and after P16 in the IC. Leu-enkephalin immunoreactivity was not transient, but
      increased progressively with age until about P21, when the adult levels were
      reached.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7625614
TI  - Cell surface glycoconjugates and the extracellular matrix of the developing mouse
      embryo epicardium.
AB  - Cell surface glycoconjugates and the extracellular matrix (ECM) of the
      proepicardium and the developing epicardium were studied in early mouse embryos
      by light and electron microscopy with histochaemical and immunocytochaemical
      techniques. The extracardially located proepicardium consists of polarized
      mesothelial cells forming the proepicardial vesicles. These vesicles contain a
      fine proteoglycan network and an acellular ECM rich in hyaluronic acid. Membrane
      bound glycoconjugates are shown with cuprolinic blue, alcian blue and ruthenium
      red on the apical (outer) cell surface, while fibronectin and laminin are present
      on the basal (luminal) cell surface. These membrane and matrix components of the
      proepicardium might be involved in specific attachment of proepicardial cells to
      the bare heart tube and might facilitate the initial migration of epicardial
      cells over the myocardial surface. In the cell coat of the cardiomyocytes of the
      bare heart tube the fibronectin and laminin are concentrated in patches. The
      formation of the epicardial covering is a rapid process, requiring only about 2
      days (9-11 days) to ensheath the entire heart tube from the inflow to the outflow
      segment. The subepicardial matrix between the newly formed epicardial covering
      and myocardial layer is acellular at first, but contains a condensing
      proteoglycan network, membrane and matrix fibronectin, type IV collagen and
      laminin on the myocardial cell surface. The formation and the distribution of the
      subepicardial ECM show regional characteristics. The accumulating ECM forms wide
      subepicardial spaces and protuberances in the atrioventricular and
      interventricular sulci. The sulci of the heart seem to provide the optimum
      microenvironment for haematopoiesis and vasculogenesis. Haematopoietic islands
      and coronary vessel forerunners appear and concentrate in the regularly spaced
      surface protuberances. The vasculogenesis proceeds from the inflow to the outflow
      segment of the heart. The first blood capillaries appear in the sinoatrial sulcus
      of the 10-day embryo. By 11-13 days the subepicardial blood vessels form an
      interconnected network and establish the coronary artery orifices.

PMID- 7625615
TI  - Sympathetic and sensory innervation of the rat shoulder joint: a WGA-HRP tracing
      and CGRP immunohistochemical study.
AB  - The innervation of the shoulder joint of the rat was investigated. Nerve origin
      was assessed by injection of a neuronal tracer (WGA-HRP) into the shoulder joint
      cavity and calcitonin gene-related peptide (CGRP), which is known to be present
      in some sensory neurons, was detected immunohistochemically with an anti-CGRP
      antibody. In the ipsilateral sympathetic and dorsal root ganglia, 133-312 and 12
      55 nerve cell bodies were respectively labeled by injection of the tracer. In the
      sympathetic ganglia, 83% of all labeled cells were found in the stellate ganglion
      and 17% in the superior cervical ganglion. In the dorsal root ganglia, 75% of the
      labeled cells were found in C4 and the neighboring ganglia (C4-C5), while the
      rest were observed in C6-8 and T3. This suggested that the origin of sensory
      innervation for the shoulder joint was mainly in the mid-cervical cord. CGRP
      immunoreactive fibers were found in the synovial capsule of the shoulder joint.
      These fibers were fine and resembled type 4 axons as classified by Brodal, i.e.,
      nerve related to pain sensation. These findings indicate that sensory nerves from
      the mid-cervical cord and sympathetic nerves from the cervical ganglion are
      distributed to the shoulder joint. It is possible that these nerves are related
      to symptoms such as pain in patients with "frozen" shoulder or other diseases.

PMID- 7625617
TI  - Basic behavioral science research for mental health. A national investment. A
      report of the National Advisory Mental Health Council.

PMID- 7625618
TI  - Animal research in psychology. More than meets the eye of the general psychology
      student.
AB  - The general psychology course provides a unique opportunity to present the
      science of psychology to a wide audience. Informing the general public about the
      importance of animal research in psychology is especially important given
      contemporary concerns about animal rights and animal welfare. A study of 8
      leading introductory psychology textbooks indicated that with the exception of
      principles of conditioning and learning, the contributions of animal research to
      psychology were often not explicitly acknowledged. In addition, major findings
      from animal research were frequently presented as if they had been obtained with
      humans. In obscuring the contributions of animal research, introductory
      psychology textbooks miss the opportunity to ensure that public policy be based
      on accurate information about the significance of this research to many areas of
      psychological science.

PMID- 7625616
TI  - Origin of the calcitonin gene-related peptide-immunoreactive nerve fibers in the
      rat shoulder joint.
AB  - The rat shoulder joint capsule is innervated by thin sympathetic and sensory
      nerve fibers, most of which contain calcitonin gene-related peptide (CGRP). In
      order to establish the origin and distribution of CGRP-immunoreactive (IR)
      fibers, wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) was
      injected into the shoulder joints of rats via a dorsal surgical approach. After
      WGA-HRP injection, the cervico-thoracic dorsal root ganglia (DRG) were removed
      and processed using both HRP histochemistry and CGRP immunohistochemistry. In the
      C4 to C7 DRG, small to medium-sized neurons (20-40 microns) were labeled by this
      combined method. The number and size of the labeled neurons were measured in the
      cervical 4th-7th DRG. The number of double-labeled neurons was one quarter of the
      total number of HRP-labeled neurons and 1/20 of the CGRP-IR neurons. Most of the
      double-labeled cells were located in the C6 ganglion, and the mean number of
      double-labeled neurons was 13 at this level. This distribution and function of
      the CGRP-IR fibers in the rat shoulder joint capsule are discussed.

PMID- 7625619
TI  - The information-processing theory of mind.

PMID- 7625620
TI  - Client as colleague. Therapeutic contracting with the seriously mentally ill.
AB  - This article introduces the therapeutic contracting program as a comprehensive
      treatment system for persons with serious mental illness. Therapeutic contracting
      offers a promising framework for integrating medical, psychological, and social
      therapies in a manner that fosters clients' active involvement in treatment. This
      article outlines a multistage therapy program that mobilizes clients'
      adaptational resources through experimental interventions, structured goal
      setting exercises, and skills-building experiences. Data illustrate the
      effectiveness of therapeutic contracting for (a) securing clients' treatment
      compliance, (b) promoting positive clinical outcomes, (c) reducing overall
      treatment costs. The therapeutic contracting model is discussed as a potential
      vehicle for expanding the professional role of psychologists in psychiatric
      settings, particularly in areas of clinical and administrative decision making.

PMID- 7625621
TI  - Abnormal rheologic effects of glyceryl trinitrate in patients with non-insulin
      dependent diabetes mellitus and reversal by antioxidants.
AB  - OBJECTIVE: To evaluate 1) the hemorrheologic and hemodynamic effects of glyceryl
      trinitrate in patients with non-insulin-dependent diabetes mellitus and 2) the
      influence of antioxidants on these effects. DESIGN: Case-control study. SETTING:
      University hospital clinic. PATIENTS: 40 patients with diabetes and no evidence
      of cardiovascular complications and 40 controls matched for demographic variables
      and body habitus. INTERVENTIONS: Sublingual glyceryl trinitrate (0.3 mg) and
      transdermal glyceryl trinitrate patches (10 mg/d). Vitamin E, 300 mg/d orally for
      7 days, and glutathione, 600 mg intravenously or intramuscularly, were given to
      test the effects of antioxidant supplementation. MEASUREMENTS: Systolic,
      diastolic, and mean arterial pressure and heart rate; left ventricular ejection
      fraction; platelet aggregation, blood viscosity, and blood filterability in vitro
      and ex vivo. RESULTS: Compared with controls, patients with diabetes had
      increased platelet aggregation to adenosine diphosphate (P < 0.005), increased
      blood viscosity (P < 0.001), and decreased blood filterability (P = 0.041) at
      baseline; blood pressure, heart rate, and ejection fraction were similar in the
      two groups. In controls, both sublingual glyceryl trinitrate and transdermal
      glyceryl trinitrate patches significantly reduced platelet aggregation (-38%; 95%
      CI, -49% to -27%) and blood viscosity (-8%; CI, -11% to -5%) and increased blood
      filterability (10%; CI, 7.0% to 13.1%). Slight but significant decreases in blood
      pressure and ejection fraction and an increase in heart rate were also seen in
      controls after administration of glyceryl trinitrate (both preparations). In
      patients with diabetes, glyceryl trinitrate paradoxically increased platelet
      aggregation (24%; CI, 15% to 33%) and blood viscosity (6%; CI, 2.9% to 8.8%) and
      decreased blood filterability (-7%; CI, -9.5% to -4.4%); hemodynamic values did
      not change significantly. In both groups, rheologic responses to glyceryl
      trinitrate (end concentration, 100 and 200 ng/mL) in vitro were similar to those
      seen in ex vivo studies. Vitamin E and glutathione normalized rheologic responses
      to glyceryl trinitrate in patients with diabetes. CONCLUSIONS: Organic nitrates
      have beneficial effects on blood rheology in controls but not in patients with
      diabetes, in whom a paradoxical deterioration is seen. Antioxidant
      supplementation can normalize primary tolerance to the rheologic effects of
      nitrates in diabetes.

PMID- 7625622
TI  - Misoprostol dosage in the prevention of nonsteroidal anti-inflammatory drug
      induced gastric and duodenal ulcers: a comparison of three regimens.
AB  - OBJECTIVE: To compare the effectiveness and tolerability of three misoprostol
      dosing regimens for the prevention of gastric and duodenal ulcers associated with
      long-term nonsteroidal anti-inflammatory drug (NSAID) therapy. DESIGN: A
      multicenter, 12-week, randomized, double-blind, placebo-controlled, parallel,
      four-limb study. PATIENTS: Eligibility criteria included upper gastrointestinal
      symptoms during NSAID therapy and no endoscopic evidence of gastric or duodenal
      ulcers. A total of 1623 patients was enrolled; 1197 of these met major accession
      and regimen-compliance criteria and completed the trial. These 1197 patients
      composed the evaluable group. INTERVENTIONS: Patients were randomly assigned to
      one of four regimens: placebo four times daily; 200 micrograms of misoprostol
      twice daily and placebo twice daily; 200 micrograms of misoprostol three times
      daily and placebo once daily; and 200 micrograms of misoprostol four times daily.
      MEASUREMENTS: Upper gastrointestinal endoscopic examinations for ulcers were done
      after 4, 8, and 12 weeks of therapy. Tolerability and safety of the regimens were
      assessed by adverse-event monitoring. RESULTS: In the placebo group, the
      incidence of gastric ulcers was 15.7% and the incidence of duodenal ulcers was
      7.5%. The incidence of gastric ulcers was significantly lower in the groups
      receiving misoprostol twice daily (8.1%; difference, 7.6% [95% CI, 2.7% to
      12.5%]; P = 0.002), three times daily (3.9%; difference, 11.8% [CI, 7.4% to
      16.3%]; P < 0.001), and four times daily (4%; difference, 11.7% [CI, 6.7% to
      16.8%]; P < 0.001) compared with placebo. The gastric ulcer rate was
      significantly higher in patients receiving misoprostol twice daily compared with
      those receiving misoprostol three times daily (difference, 4.2% [95% CI, 0.7% to
      7.7%]; P = 0.02). A significant (P = 0.02) misoprostol dose-response effect was
      noted in the prevention of gastric ulcers. The incidence of duodenal ulcers was
      significantly lower in the groups receiving misoprostol twice daily (2.6%;
      difference, 4.9% [CI, 1.5% to 8.2%]; P = 0.004), three times daily (3.3%;
      difference, 4.2% [CI, 0.6% to 7.7%]; P = 0.019), and four times daily (1.4%;
      difference, 6.1% [CI, 2.6% to 9.6%]; P = 0.007) compared with placebo. No
      significant difference was detected between patients receiving misoprostol twice
      daily and those receiving misoprostol three times daily, and no dose-response
      effect was noted with duodenal ulcers. The incidence of withdrawals for adverse
      events was significantly lower in the groups receiving misoprostol twice daily
      (12%) and three times daily (12%) than in the group receiving it four times daily
      (20%). The incidence of gastrointestinal adverse events was significantly higher
      in the group receiving misoprostol four times daily (74%) than in the placebo
      group (62%). CONCLUSION: Misoprostol, 200 micrograms twice or three times daily,
      offers substantial protection against gastric and duodenal ulcers in patients
      receiving long-term NSAID therapy. These dosages were better tolerated than the
      currently approved regimen of 200 micrograms four times daily.

PMID- 7625623
TI  - Isolated chloroma: the effect of early antileukemic therapy.
AB  - OBJECTIVE: To evaluate the effect of antileukemic chemotherapy administered at
      diagnosis on the survival of patients with isolated chloroma. DESIGN:
      Retrospective review of locally identified patients and analysis of cases from
      the medical literature. PATIENTS: The records of all patients with isolated
      chloroma identified at three teaching hospitals in Toronto between 1980 and 1994
      were reviewed. A MEDLINE search was done to identify all cases of isolated
      chloroma reported in the English-language medical literature. Patients with a
      previous known hematologic disorder were excluded. MEASUREMENTS: The effect of
      therapy on 1) the interval between diagnosis of chloroma and diagnosis of acute
      myeloid leukemia and 2) survival was determined. RESULTS: 7 local patients and 83
      published cases were identified, for a total of 90 evaluable patients. For the
      entire group, the median time to the diagnosis of acute myeloid leukemia was 9
      months, and median survival was 22 months. Chemotherapy was administered to 49
      patients (54%) at diagnosis of chloroma. Significantly fewer patients treated
      with chemotherapy subsequently developed acute myeloid leukemia (41% compared
      with 71%; P = 0.001). Survival was longer in patients treated with chemotherapy
      (> 50% alive with a median follow-up of 25 months compared with a median survival
      of 13 months for those initially untreated; P = 0.001). Multivariate analysis
      showed that neither local radiotherapy nor surgery had an effect on survival.
      CONCLUSIONS: Administration of antileukemic chemotherapy at diagnosis of chloroma
      is associated with a significantly lower probability of developing acute myeloid
      leukemia and with longer survival.

PMID- 7625624
TI  - Alopecia associated with fluconazole therapy.
AB  - OBJECTIVE: To describe the association between fluconazole and reversible
      alopecia. DESIGN: A retrospective survey of 1) patients enrolled in NIAID Mycoses
      Study Group (MSG) protocols involving the long-term use of fluconazole for
      treatment of endemic mycoses and 2) patients treated with fluconazole outside of
      a protocol setting but by the MSG investigators who were MSG members. SETTING: 26
      MSG sites in the United States. PATIENTS: 33 patients with various deep and
      superficial mycoses who developed alopecia while receiving fluconazole. RESULTS:
      11 of 26 investigators reported a total of 33 patients with substantial alopecia
      related to fluconazole therapy. Underlying mycoses included blastomycosis,
      sporotrichosis, histoplasmosis, cryptococcosis, coccidioidomycosis, and mucosal
      candidiasis. In separate MSG studies, 17 of 136 (12.5%) and 8 of 40 (20%)
      patients had substantial reversible alopecia associated with fluconazole therapy.
      Eight patients who were not in the protocol had similar adverse effects. Twenty
      nine of 33 patients (88%) received at least 400 mg of fluconazole daily for a
      mean of 7.1 months. Alopecia developed a median of 3 months after initiation of
      fluconazole therapy and involved the scalp in all patients. Other sites were
      involved in about one third of patients. Three patients required wigs because of
      extensive hair loss. Alopecia resolved within 6 months of discontinuation of
      fluconazole therapy or reduction of the daily dose by at least 50%. CONCLUSIONS:
      Alopecia appears to be a common adverse event associated with higher-dose (400
      mg/d) fluconazole given for 2 months or longer. This effect may be severe but is
      reversed by discontinuing fluconazole therapy or substantially reducing the daily
      dose.

PMID- 7625625
TI  - Beta-blockers and sudden cardiac death.
AB  - OBJECTIVES: To 1) consider the problem of sudden death from heart disease and the
      role of beta-blockers and other agents in preventing sudden death and 2) review
      perceived problems with beta-blocker therapy, such as effects on blood lipids,
      complications in diabetes, and adverse effects on heart failure and quality of
      life. DATA SOURCES: MEDLINE and EMBASE searches done from July 1994 on, and
      recognized texts. STUDY SELECTION: More than 400 original and review articles
      were evaluated, of which the most relevant were selected. DATA EXTRACTION: Data
      were extracted and reviewed by two authors. Accuracy was confirmed, when
      necessary, by the other authors. DATA SYNTHESIS: Of all of the therapies
      currently available for the prevention of sudden cardiac death, none is more
      established or more effective than beta-blockers. Indeed, the evidence that beta
      blockers have a cardioprotective effect is compelling. They probably reduce the
      rate of atheroma formation; they reduce the risk for ventricular fibrillation in
      animal models of myocardial ischemia; they appear to reduce cardiac mortality in
      primary prevention trials; and they reduce mortality, particularly from sudden
      death, in patients who have had infarction. Moreover, withholding beta-blockers
      because of problems perceived to be associated with them is usually not warranted
      and may frequently prevent their use in those who will benefit most from them.
      CONCLUSION: Clinicians should reappraise the evidence for the significant effect
      of beta-blockers on morbidity and mortality, and they should recognize the
      importance of initiating and maintaining beta-blocker therapy when the less well
      informed might suggest otherwise.

PMID- 7625627
TI  - Diagnostic tests for hepatitis C: where are we now?

PMID- 7625626
TI  - Antiviral therapy for human papillomaviruses: rational and prospects.
AB  - OBJECTIVE: To review the basic virology of human papillomavirus (HPV) and the
      natural history of HPV infection and to discuss current and potential therapies.
      DATA SOURCES: The MEDLINE database (1966 to 1994) was searched to identify
      English-language articles and abstracts on HPV biology and antiviral
      chemotherapy. STUDY SELECTION: Peer-reviewed basic science and clinical research
      studies on the molecular, cellular, and human biology of HPV infection. DATA
      EXTRACTION: Summaries of data from research studies on the biology of
      papillomavirus infection and information from review articles on the basic and
      applied pharmacology of antiviral agents. DATA SYNTHESIS: Papillomavirus
      infections are very common. Human papillomavirus infections may be asymptomatic
      or may be manifested in various benign or malignant lesions, most notably
      anogenital condyloma and anogenital carcinoma. Currently, therapeutic options for
      HPV infection are limited, expensive, and often ineffective. By understanding the
      basic virology and natural history of HPV infection, potential sites for
      pharmacologic intervention can be identified. Although currently available
      antiviral compounds are inactive against HPV, they serve as models for the
      rational design of HPV antiviral drugs. CONCLUSIONS: Although HPV infection
      causes substantial morbidity and expense, uniformly effective therapy for HPV
      infection is not currently available. Several processes in the HPV infection
      cycle are appropriate targets for the development of antiviral agents. The
      development of compounds active against HPV could prevent the benign and
      malignant diseases associated with HPV infection.

PMID- 7625628
TI  - An organized sense of wonder. From the president's convocation address at the
      American College of Physicians annual session, 16 March 1995.

PMID- 7625629
TI  - Diagnosing at the mall.

PMID- 7625630
TI  - Aspirin and colorectal cancer.

PMID- 7625631
TI  - Aspirin and colorectal cancer.

PMID- 7625632
TI  - Minocycline in rheumatoid arthritis.

PMID- 7625633
TI  - Minocycline in rheumatoid arthritis.

PMID- 7625634
TI  - Minocycline in rheumatoid arthritis.

PMID- 7625636
TI  - Minocycline and rheumatoid arthritis revisited.

PMID- 7625635
TI  - Heart rate alternans.

PMID- 7625637
TI  - Primary pulmonary hypertension in association with human T-cell lymphotropic
      virus type I in a hemophiliac.

PMID- 7625638
TI  - Avoiding the ciprofloxacin-didanosine interaction.

PMID- 7625639
TI  - AIDS Clinical Trials Group study numbers.

PMID- 7625641
TI  - Combined Vaccines and Simultaneous Administration: Current Issues and
      Perspectives. Conference proceedings. Bethesda, Maryland, July 28-30, 1993.

PMID- 7625640
TI  - Overview--combination vaccines and simultaneous administration. Past, present,
      and future.

PMID- 7625642
TI  - Combined and simultaneously administered vaccines. A brief history.

PMID- 7625643
TI  - FDA perspective on regulatory issues in vaccine development.

PMID- 7625644
TI  - Combination vaccines for diphtheria, tetanus, pertussis, and Haemophilus
      influenzae type b.
AB  - The ability to combine the standard DTP and Haemophilus b conjugate vaccine
      considerably simplifies the childhood immunization schedule and process. In
      addition to reducing the number of immunizations by half, the combination product
      reduces administrative aspects associated with vaccination including tracking.
      Simplification of the immunization process should have a positive impact on the
      vaccine delivery and utilization. Perhaps more importantly, an ability to create
      combination vaccines will be critical for inclusion of new antigens appropriate
      for infant vaccines. The combination of DTP and HbOC reduces the number of
      immunizations routinely given at 2, 4, and 6 months of age by half. Since it is
      unlikely that parents or pediatricians will accept more than two shots per visit,
      this reduction is critical. As new vaccines are licensed for such important
      childhood pathogens as Streptococcus pneumoniae and respiratory syncytial virus,
      designing stable combination products will become even more critical. Having
      stated that, we must also not lose site of the fact that combination products
      must meet the criteria for stability, safety, and efficacy comparable to the
      separately delivered products. These considerations are not trivial. In the
      development of Tetramune (DTP-HbOC), stability of the product and consistency of
      the immune response were critical design parameters for both the preclinical and
      clinical research. Likewise, the experience with other DTP-Haemophilus b
      combinations has shown that simple mixing of products prior to injection can
      reduce the immune response in ways that are not necessarily predictable. In
      contrast, the response to each of the components of Tetramune was in fact higher
      than when the vaccines were given separately. This increased response to all of
      the antigens was not anticipated based on the vaccine composition and points to
      the need for not only physical characterization of new combinations, but also
      clinical testing of final combined products before they are introduced for
      routine use.

PMID- 7625645
TI  - The biochemistry and cell biology of antigen presentation by MHC class I and
      class II molecules. Implications for development of combination vaccines.
AB  - T lymphocytes play a central role in adaptive immunity. They provide direct
      effector function, regulate the activity of non-antigen-specific effector cells
      such as macrophages, and control the production of antibodies by B cells. Thus,
      the proper stimulation of T cells is critical to effective vaccination. T cells
      bearing alpha beta receptors are stimulated by antigen-derived peptides displayed
      on cell surfaces bound to highly polymorphic, major histocompatibility complex
      encoded glycoproteins. To elicit suitable T cell responses vaccines must,
      therefore, contain proteins or peptides derived from the organism against which
      protection is desired, the pathogen-derived peptides must be capable of
      interacting with the allelic forms of the MHC molecules expressed in the
      vaccinated individuals, and the vaccine components must be delivered in a manner
      that ensures they are made available for binding to the MHC molecules on
      appropriate antigen-presenting cells. This paper has reviewed the rules governing
      peptide binding to MHC molecules, the intracellular pathways of protein
      synthesis, protein degradation, and protein and peptide transport involved in
      bringing together antigenic peptides and MHC molecules, and the distinct function
      of MHC class I versus class II molecules. The implications of this knowledge for
      effective combined vaccine design and delivery were considered.

PMID- 7625646
TI  - Vaccine strategies: targeting helper T cell responses.
AB  - Vaccine strategies need to take into account the balance of T helper subsets they
      induce. TH1 cells, which secrete IFN gamma and IL-2, are associated with CMI,
      rather than humoral responses, and afford protection against intracellular
      infections including parasites. In contrast, TH2 cells secrete IL-4, IL-5, and IL
      10; elicit high-titer antibody responses and poor CMI; and are associated with
      susceptibility to infection with intracellular pathogens. Depending on the type
      of TH cell bias required, it is possible to manipulate the immune response to a
      protein or peptide by employing (1) different adjuvants, (2) conjugating the
      protein to various carriers, (3) immunizing in the presence of cytokines, (4)
      using alternative routes of administration, or (5) using different forms or doses
      of antigen. To apply these approaches to a particular vaccine, it is necessary to
      identify which component of the infectious agent (e.g., envelope protein or
      peptide) or allergen to target. Once the type of TH cell response that is
      protective is identified, it may be possible to combine a protein with an
      adjuvant or link it to a carrier that will promote responses towards the most
      advantageous TH subset.

PMID- 7625647
TI  - The role of sIgA+ B cells in oral immunity.

PMID- 7625648
TI  - Liposomal vaccines: clinical status and immunological presentation for humoral
      and cellular immunity.
AB  - Liposomes have been proposed as vehicles for vaccines against parasitic and viral
      illnesses. Experimental vaccines against malaria, HIV, hepatitis A, and influenza
      virus have been shown to be safe and highly immunogenic in several human trials.
      Analysis of the intracellular trafficking patterns of liposomal antigen reveals
      that after being phagocytosed by macrophages, liposomal antigen readily escapes
      from endosomes into the cytoplasm of the macrophages. It is proposed that
      liposomal peptide antigen can enter either the Golgi apparatus or the endoplasmic
      reticulum and thereby interact with MHC class II or class I molecules. The
      intracellular cytoplasmic trafficking patterns of liposomal antigens raise the
      possibility that liposomes may have utility in human vaccines for induction of
      either humoral immunity or cytotoxic T lymphocytes.

PMID- 7625649
TI  - Immunologic adjuvants for modern vaccine formulations.
AB  - Optimization of the immunogenicity of many new-generation vaccine formulations,
      including combination vaccines, will require the use of immunologic adjuvants
      other than the aluminum compounds in today's licensed vaccines. The selection of
      adjuvants for use in vaccine formulation may be as critical as the choice of the
      vaccine antigens themselves in providing optimal efficacy for the target
      populations, vaccine compliance, and cost. Adjuvants have diverse mechanisms of
      action and must be selected for use based on the immune responses desired for a
      particular candidate vaccine. Recent advances in the number and variety of
      adjuvants available for clinical evaluation coupled with the increased
      understanding of their mechanisms of action encourage the inclusion of adjuvants
      as part of rational vaccine design. Finally, the proposed standardized methods to
      evaluate adjuvant safety should be implemented for human candidate vaccines
      formulated with novel adjuvants.

PMID- 7625650
TI  - Designing peptide vaccines to broaden recognition and enhance potency.

PMID- 7625651
TI  - Galactose oxidation as a potent vaccine adjuvant strategy. Efficacy in murine
      models and in protection against a bovine parasitic infection.
AB  - Potent immunological adjuvants are urgently required to complement subunit
      protein and peptide vaccines in prophylactic and therapeutic vaccination.
      Carbonyl-amino condensations, which are essential to the inductive interaction
      between antigen-presenting cells and T-helper cells, were tested as a target for
      the enhancement or immune responses to vaccine antigens. Enzymic oxidation of
      cell surface galactose by the novel adjuvant NAGO, to increase amine-reactive
      carbonyl groups on lymphocytes and antigen-presenting cells, provided a potent
      noninflammatory method of enhancing the immunogenicity of viral, bacterial, and
      protozoal subunit vaccines in mice. In pilot protection studies with a
      glutathione-S-transferase vaccine against bovine Fasciola hepatica, a formulation
      containing NAGO as sole adjuvant agent proved very effective in inducing
      protection. In terms of protection in individual animals, NAGO alone was better
      than Quil A emulsified in squalene Montanide (five of eight animals were
      protected better than 80% by NAGO; four of eight animals were protected better
      than 93% by NAGO; two of eight animals were protected better than 80% by QA/SM).
      QA/SM (69% mean protection) was, however, more consistent overall than NAGO (65%
      mean protection). NAGO proved more effective in murine models when combined with
      muramyl dipeptide, but this combination has yet to be tested in protection
      studies.

PMID- 7625652
TI  - Strategies for developing combination vaccines.

PMID- 7625653
TI  - Yeast retrotransposon particles as antigen delivery systems.
AB  - The development of technologies to produce recombinant proteins for use in the
      pharmaceutical industry has made substantial advances, in particular in the area
      of generating antigens containing multiple copies of important immunological
      regions. One such antigen-carrier system is based on the ability of a protein
      encoded by the yeast retrotransposon, Ty, to self-assemble into virus-like
      particles. Ty-fusion proteins retain this ability to form particles, and a range
      of hybrid VLPs carrying a variety of heterologous antigens have been produced and
      shown to induce potent immune responses. In particular, hybrid VLPs carrying the
      core protein p24 of HIV (p24-VLPs) have been shown to induce antibody and T-cell
      proliferative responses in both experimental animals and human volunteers, and
      immunization of rabbits with VLPs carrying the principal neutralizing determinant
      of HIV (V3-VLPs) resulted in the induction of neutralizing antibody responses and
      T-cell proliferation. Further studies with V3-VLPs have shown that this
      particulate antigen stimulates enhanced V3-specific lymphoproliferative responses
      as compared to whole recombinant gp120 or to V3 peptide conjugated to albumin.
      The V3-VLPs also induce potent CTL responses following immunization of mice in
      the absence of adjuvant. These responses are MHC class I restricted and are
      mediated by CD8-positive cells. These observations therefore demonstrate that
      hybrid Ty-VLPs induce both humoral and cellular immune responses against HIV and
      suggest that these immunogens may be important in combatting AIDS and other
      infections.

PMID- 7625654
TI  - Progress on development of the live BCG recombinant vaccine vehicle for combined
      vaccine delivery.
AB  - BCG, the current vaccine for tuberculosis, has been administered to approximately
      three billion people. This live vaccine has a low incidence of serious side
      effects and can be given at birth. Within the past six years, systems for the
      manipulation and expression of foreign genes in mycobacteria have been developed,
      allowing the evaluation of rBCG as a vaccine delivery vehicle for heterologous
      antigens. Recent studies from our group have shown that rBCG expressing outer
      surface protein A of Borrelia burgdorferi can completely protect mice from an
      intradermal challenge with this organism. Immune responses protective against
      Streptococcus pneumoniae challenge have also been achieved by immunization of
      mice with rBCG expressing PspA. The simplest means of administering multiple
      vaccine antigens in a rBCG vehicle would be to coexpress these simultaneously in
      the same BCG recombinant. Currently two general classes of vectors exist for the
      expression of foreign proteins in BCG: shuttle plasmid vectors, which replicate
      extrachromosomally in mycobacteria, and shuttle "phasmid" vectors, which
      integrate as a single copy into the mycobacterial chromosome by means of vector
      encoded integration functions of the lysogenic mycobacteriophage L5. The genetic
      capacity of the multicopy plasmid vectors may be 20 kb or more, while the
      potential exists for stable integration of much larger amounts of DNA into the
      mycobacterial genome (L5 itself is 52 kb). Additionally, these two expression
      systems can have the compatibility to coexist in a single BCG cell. Otitis media
      is caused by infections of the middle ear chiefly with either S. pneumoniae or H.
      influenzae. Thus, an effective vaccine would necessarily include antigens from
      both these pathogens. Our initial attempt at construction of a BCG multivaccine
      vehicle was to express proteins from each of these pathogens from the same
      multicopy plasmid. We have recently succeeded in coexpressing the S. pneumoniae
      PspA and H. influenzae PAL proteins in BCG. Future work will address how the
      biochemical characterization of and immune responses to the recombinant antigens
      of the "bivalent" rBCG:PspA/PAL vaccine compare to those of the respective
      "monovalent" rBCG vaccines.

PMID- 7625655
TI  - Live attenuated vaccinia and other poxviruses as delivery systems: public health
      issues.

PMID- 7625656
TI  - Manufacturing issues for multivalent vaccines.

PMID- 7625657
TI  - Issues in design of clinical trials of combination vaccines.

PMID- 7625658
TI  - Industry perspective on clinical trial issues for combination vaccines.
AB  - The development and production of vaccines remains complicated, largely because
      of the complexity of the vaccines, which are virtually always manufactured in a
      biological system; the nature of most vaccines precludes the use of the detailed
      chemical analysis that is possible for simple chemical entities. Therefore,
      approval and release of vaccines is dependent upon careful view of the
      manufacturing processes, the analytical data that are available, and data from
      clinical trials of consistency lots. The makeup of consistency lots from
      combinations, the purpose and utility of such lots, and the timing of their
      production depend not only on the maturity of the manufacturing process but also
      upon mutual agreement between the sponsor and the regulators. Consistency of
      application of regulations and precedent are important in the sponsor's ability
      to carry out successful development programs. The science of adjuvants is still
      in its infancy, but opportunities for it to mature are legion. Aluminum salts
      remain the mainstay of contemporary adjuvants but will no doubt be supplanted in
      the near future. The ethics of doing efficacy studies in infants who could be
      protected by safe and well-tolerated vaccines must be debated openly. Closely
      related to efficacy studies are the use of surrogates, which should be developed,
      recognized, and utilized. Finally, the potential utility of M-M-R IIV was shown
      by studies of the individual attenuated virus components in vaccines.

PMID- 7625659
TI  - Practical considerations regarding the impact on immunization schedules of the
      introduction of new combined vaccines.

PMID- 7625662
TI  - Combination vaccines: regulatory issues.

PMID- 7625661
TI  - International prospects for combined vaccines with emphasis on quadrivalent
      diphtheria-tetanus-pertussis-hepatitis B vaccine.

PMID- 7625660
TI  - Interactions between PRP-T vaccine against Haemophilus influenzae type b and
      conventional infant vaccines. Lessons for future studies of simultaneous
      immunization and combined vaccines.

PMID- 7625663
TI  - Defining surrogate serologic tests with respect to predicting protective vaccine
      efficacy: pertussis vaccination.
AB  - The first efficacy trial of pertussis vaccines with defined purified antigens
      failed to demonstrate a serologic correlate of protection, although both tested
      vaccines were shown to give significant protection against typical whooping
      cough. The antibody response to pertussis toxoid was dose dependent. A lower anti
      PT response in the two-component vaccine, containing one-half the amount of PT in
      the one-component vaccine, seemed to be compensated by a significant anti-FHA
      response, since both vaccines conferred similar protection against typical
      illness. However, the immunologic mechanisms whereby protection is conferred
      remain unclear. At present antibody responses to the antigens included in the
      first tested vaccines could be used as pseudoindicators of protection. The group
      of vaccinated infants who were protected did differ in their antibody profile as
      compared to unvaccinated infants. Tentatively, candidate vaccines should elicit
      no less antibody responses to PT and FHA as those elicited by the above one- and
      two-component vaccines, respectively. The response to other antigens such as
      pertactin and fimbriae cannot be related to protection at present. Ongoing
      efficacy trials of a number of pertussis vaccines of varying composition may or
      may not provide immunological correlates of protection against pertussis. The
      trials ought to be subjected to a preplanned, independent (meta)analysis with
      defined end points to increase the understanding of the contribution of various
      antigens to the protective efficacy of pertussis vaccines.

PMID- 7625664
TI  - Laboratory correlates of protection against Haemophilus influenzae type b
      disease. Importance of assessment of antibody avidity and immunologic memory.
AB  - The concentration of serum antibody to the Haemophilus influenzae type b
      polysaccharide sufficient to confer protection against Hib disease has been
      estimated to range from 0.15 to 1.0 microgram/ml as measured by conventional
      antigen binding assays. However, the ability of these serologic tests to predict
      vaccine equivalence and/or protective efficacy is limited since there are
      important qualitative differences in vaccine-induced anti-PRP antibody, such as
      isotype, variable region usage, and antibody avidity. These differences may
      profoundly affect the biologic activity of the antibody. Also, Hib conjugate
      vaccination primes infants for memory antibody responses to a subsequent
      encounter with PRP, and immunologic priming can occur in infants with very low
      serum anti-PRP antibody responses to conjugate vaccination, or in those whose
      antibody concentrations have declined after vaccination. Primed infants are
      likely to be protected against Hib disease in the absence of "protective" serum
      antibody concentrations because priming permits a rapid serum anti-PRP antibody
      response upon encountering the organism. Thus, quantitative assessment of
      immunogenicity, by itself, is insufficient to predict vaccine equivalence or
      protective efficacy. In defining surrogate serologic tests for prediction of
      vaccine efficacy, assessments of antibody avidity and induction of immunologic
      memory should be included. Ideally, these assessments should be supplemented with
      antibody functional assays such as complement-mediated bactericidal activity,
      opsonic activity, or passive protection in animal models of disease.

PMID- 7625665
TI  - Defining surrogate serologic tests with respect to predicting protective vaccine
      efficacy: poliovirus vaccination.
AB  - Inactivated and trivalent oral poliovirus vaccines contain either formalin
      inactivated or live, attenuated poliovirus, respectively, of the three serotypes.
      Interference among the three attenuated poliovirus serotypes was minimized with a
      "balanced-formulation" vaccine, and serologic responses after IPV were optimized
      by adjusting the antigenic content of each inactivated poliovirus serotype.
      Seroconversion is dependent on both the relative content as well as the absolute
      quantity of virus in the vaccine. The "gold standard" method to assess humoral
      antibody responses following vaccination is the neutralization assay. Any
      detectable titer of neutralizing antibody against poliovirus is considered
      protective against clinical paralytic diseases. Recently, standard procedures
      were adopted for conducting neutralization assays. Efforts are being undertaken
      now to develop a combined diphtheria and tetanus toxoids and pertussis vaccine
      and IPV vaccine in the United States using a dual-chambered syringe that mixes
      the content of both vaccines at the time of injection; this approach is necessary
      to overcome the potential detrimental effect of thimerosal on IPV (the
      preservative in DTP). Other vaccines that combine DTP and/or Haemophilus
      influenzae type b and/or hepatitis B with IPV appear feasible but require further
      investigation. New combination vaccines should induce similar or superior levels
      of neutralizing antibody in serum for individual protection against paralytic
      disease and mucosal immunity that effectively decreases viral replication in the
      intestine and pharynx for population protection against transmission of
      poliovirus.

PMID- 7625666
TI  - Methodological issues in the evaluation and monitoring of vaccine safety.

PMID- 7625667
TI  - Surveillance of the safety of simultaneous administration of vaccines. The
      Centers for Disease Control and Prevention experience.

PMID- 7625668
TI  - Similarity/equivalence trials for combination vaccines.
AB  - In a similarity or "equivalence" trial of a combination vaccine, we wish to show
      that the combination is sufficiently similar to the separately administered
      components in some measure of safety, immunogenicity, or efficacy to justify use
      of the combination. In this setting it is usually required to show similarity in
      one direction only; specifically, we design the trial to rule out superiority of
      the separate components by as much as a prespecified quantity theta 0 in an
      appropriate outcome measure (e.g., a difference or ratio). It is crucial that
      theta 0 be chosen to be clinically meaningful, so that any difference or ratio
      less than theta 0 is truly acceptable to clinicians. Estimation is generally more
      relevant than hypothesis testing in such a trial, and consequently it is natural
      to consider design and analysis in terms of confidence intervals. The same sample
      sizes can be obtained, however, from a hypothesis testing approach. The
      appropriate null hypothesis is that the separate components are superior to the
      combination by at least theta 0, with rejection of the hypothesis supporting a
      conclusion of similarity. It is not appropriate to design the trial to test the
      null hypothesis of no difference, as we would do if we wished to demonstrate
      superiority of the combination vaccine; failure to reject that hypothesis does
      not prove similarity, and we might reject the hypothesis when the true difference
      is unimportant clinically. Further, this inappropriate approach may result in a
      sample size either larger or smaller than necessary. Sample size formulations are
      available for various types of comparative measures, e.g., a difference of
      normally distributed means, a difference or ratio of proportions, and a ratio of
      hazards.

PMID- 7625669
TI  - The statistical analysis of immunogenicity data in vaccine trials. A review of
      methodologies and issues.

PMID- 7625670
TI  - Combination live enteric virus vaccines.

PMID- 7625671
TI  - Potential alterations in immunogenicity by combining or simultaneously
      administering vaccine components.

PMID- 7625672
TI  - Combination live respiratory virus vaccines.

PMID- 7625673
TI  - Progress and challenges for a new combination vaccine composed of diphtheria,
      tetanus, acellular pertussis, and Haemophilus b conjugate.

PMID- 7625674
TI  - Surrogate serologic tests for the prediction of pertussis vaccine efficacy.

PMID- 7625675
TI  - Comprehensive evaluation of vaccine safety. Assessment of local and systemic side
      effects as well as emergency and hospital utilization.

PMID- 7625676
TI  - Vaccine licensure: a proposal to meet changing needs.

PMID- 7625677
TI  - Utility of large-linked databases in vaccine safety, particularly in
      distinguishing independent and synergistic effects. The Vaccine Safety Datalink
      Investigators.

PMID- 7625678
TI  - Combination vaccines: some practical considerations.

PMID- 7625679
TI  - A perspective on issues relating to future vaccines.

PMID- 7625680
TI  - Determinant flanking regions and the design of appropriate vaccines.

PMID- 7625681
TI  - Selection of carrier and B cell protectope sequences for vaccines.

PMID- 7625683
TI  - Definition and clinical assessment of consistency lots for combination vaccines.

PMID- 7625682
TI  - Prevention of systemic infections caused by group B streptococcus and
      Staphylococcus aureus by multivalent polysaccharide-protein conjugate vaccines.

PMID- 7625684
TI  - Immune responses to pertussis vaccines concurrently administered with viral
      vaccines.

PMID- 7625686
TI  - Forty years of DNA.

PMID- 7625685
TI  - Comparative evaluation of immunization with live attenuated and inactivated
      poliovirus vaccines.
AB  - The development of serum and nasopharyngeal antibody response, as well as the
      magnitude and temporal pattern of fecal shedding of vaccine and revertant polio
      viruses, have been examined in infants previously immunized with one or more
      doses of orally administered live attenuated poliovaccine, enhanced potency
      inactivated polio-vaccine, or both. The nature of serum immune response appears
      to be similar after either immunization schedule, although the antibody titers
      are quantitatively higher after two doses of EP-IPV than those observed after a
      similar schedule with OPV. Highest antibody activity is generally detected in
      subjects immunized with a combination of EP-IPV followed by OPV. ELISA antibody
      activity in the nasopharynx was regularly detected after either form of
      immunization. However, neutralizing and VP3 poliovirus virion protein-specific
      antibody responses in the nasopharynx were consistently observed in subjects
      immunized with OPV or EP-IPV followed by OPV. Subjects immunized with EP-IPV
      alone exhibit significantly lower or absent neutralizing or VP3-specific
      responses. The nucleic acid sequences of the purified RNA obtained from all virus
      isolates have also been examined in the 5' noncoding region by dideoxy-sequencing
      to determine whether the viruses shed represent revertants (vaccine), non
      revertants, or both. The frequency and duration of vaccine virus shedding appears
      to be similar in both immunization schedules. Revertant virus shedding was not
      demonstrated 30 days after immunization with OPV alone. However, shedding of
      revertants was detected for as long as 60 days in some subjects previously
      immunized with EP-IPV. The duration of shedding of revertant virus differed with
      different serotypes and different immunization regimens. Prior immunization with
      one or more doses of OPV reduced the length of shedding of revertant virus.
      Significantly, however, prior immunization with one or more doses of EP-IPV was
      not associated with reduced shedding of revertant virus types. Based on these
      observations and a number of other epidemiologic data summarized in this review,
      it is clear that both OPV and EP-IPV when used alone are highly effective and
      safe in inducing effective immunity to polio-virus and in the eradication of
      poliomyelitis. While the combination schedule employing EP-IPV followed by OPV
      should result in a decline of vaccine-associated paralytic (VAP) disease in OPV
      recipients, such immunization schedules may have little or no impact on the
      development of VAP in susceptible contacts. Furthermore, the logistics and the
      cost of combination schedules must be considered before current recommendations
      based on the use of OPV or EP-IPV alone are revised.

PMID- 7625687
TI  - DNA: The Double Helix--Forty Years: Perspective and Prospective. Conference
      proceedings. Chicago, Illinois, October 13-16, 1993.

PMID- 7625688
TI  - Molecular structure of nucleic acids. A structure for deoxyribose nucleic acid.
      1953.

PMID- 7625689
TI  - Molecular structure of nucleic acids. Molecular structure of deoxypentose nucleic
      acids. 1953.

PMID- 7625690
TI  - Gene regulatory proteins and their interaction with DNA.
AB  - The selective expression of a gene is achieved through the interaction of protein
      transcription factors with characteristic DNA sequences located in the regulatory
      region of the gene, which is usually distinct from the coding region. These
      proteins contain domains that bind specifically to the DNA sites (or response
      elements). Some general principles in the design of these DNA-binding domains are
      described, followed by examples of the different structural classes discovered so
      far and how they recognize their binding sites.

PMID- 7625691
TI  - Molecular structure of nucleic acids. Molecular configuration in sodium
      thymonucleate. 1953.

PMID- 7625692
TI  - Mammalian learning and memory studied by gene targeting.

PMID- 7625693
TI  - Circuits.

PMID- 7625694
TI  - The NK-2 homeobox gene and the early development of the central nervous system of
      Drosophila.

PMID- 7625695
TI  - The molecular basis for phenotypic diversity of genetic disease.

PMID- 7625696
TI  - The aperiodic crystal of heredity.

PMID- 7625697
TI  - A molecular switch for the consolidation of long-term memory: cAMP-inducible gene
      expression.

PMID- 7625698
TI  - Molecular analysis of Duchenne muscular dystrophy: past, present, and future.

PMID- 7625699
TI  - Transgenic mouse models of disease: altering adipose tissue function in vivo.

PMID- 7625700
TI  - Recombinant DNA technology and oral medicine.

PMID- 7625702
TI  - A nuclear tyrosine kinase becomes a cytoplasmic oncogene.

PMID- 7625701
TI  - The molecular basis of oncogenes and tumor suppressor genes.

PMID- 7625703
TI  - Recombinant toxins: new therapeutic agents for cancer.

PMID- 7625704
TI  - DNA: template for an economic revolution.

PMID- 7625705
TI  - The molecular biology of thyroid hormone action.

PMID- 7625706
TI  - Human and mouse T-cell receptor loci: genomics, evolution, diversity, and
      serendipity.

PMID- 7625707
TI  - Where will genome analysis lead us forty years on?

PMID- 7625708
TI  - The world we have lost.

PMID- 7625709
TI  - A fifty-year perspective on the genetic role of DNA.

PMID- 7625710
TI  - DNA in the decade before the double helix.

PMID- 7625711
TI  - Linus Pauling: chemist and molecular biologist.

PMID- 7625712
TI  - Historic reflections on the clinical roots of molecular biology.

PMID- 7625713
TI  - Steroid hormone antagonists. Summary and future challenges.

PMID- 7625714
TI  - Steroid Receptors and Antihormones. Conference proceedings. Dallas, Texas,
      September 20-23, 1994.

PMID- 7625715
TI  - A new interpretation of antiestrogen action.
AB  - Despite differences in their pharmacological behavior, type I and type II
      antiestrogens have certain important properties in common. Both differ from
      estradiol in that they enhance the immunoreactivity of estrogen receptors,
      apparently by inducing conformational change that exposes an additional epitope
      for a particular monoclonal antibody. Moreover, both types of antihormones not
      only compete with estradiol for its binding to the receptor but they also react
      with another domain not recognized by the hormone. The binding capacity for
      either type of antiestrogen is nearly twice that for estradiol, providing
      definitive evidence for the existence of specific antiestrogen-binding sites that
      are postulated to be important in antagonist action. These findings suggest a
      unified two-site model which helps explain how the same substance can be both an
      agonist and an antagonist; why there may be species variations in the
      agonist/antagonist relationship of type I compounds; and why type II agents show
      only antagonistic properties. It is suggested that interaction with secondary,
      antagonist-specific binding sites may provide a useful screen in the search for
      new and improved antihormonal agents.

PMID- 7625716
TI  - Cellular mechanisms which distinguish between hormone- and antihormone-activated
      estrogen receptor.
AB  - The use of reverse genetics has permitted a definition of the structural features
      within estrogen receptor required for its productive association with the
      transcription apparatus. These sequences, transactivation function 1 (TAF1) in
      the amino terminus and TAF2 at the carboxyl terminus, display distinct
      transcriptional functions. Using specific receptor mutations it has been shown
      that on some promoters both TAF1 and TAF2 are required for maximal
      transcriptional activity, whereas on others, additional factors bound to the
      target promoter can functionally substitute for TAF1 or TAF2. Estrogen functions
      as an ER agonist by promoting functional synergism between TAF1 and TAF2.
      Conversely, 4-OH-tamoxifen inhibits TAF2 activity and functions as an antagonist
      in cell contexts where TAF2 is required. Alternatively, if a 'TAF2 function' is
      supplied by another factor, 4-OH tamoxifen can manifest ER agonist activity.
      These data indicate that alterations in the cellular expression of proteins which
      mimic TAF1 or TAF2 activity can have a profound effect on the pharmacology of ER
      modulators. Thus the identification of the cellular proteins which interact with
      ER and its TAF regions will allow a definition of the mechanism used by the cell
      to distinguish between hormone- and antihormone-activated estrogen receptor.

PMID- 7625717
TI  - A mutant receptor as a mechanism of drug resistance to tamoxifen treatment.

PMID- 7625718
TI  - Responses to pure antiestrogens (ICI 164384, ICI 182780) in estrogen-sensitive
      and -resistant experimental and clinical breast cancer.

PMID- 7625720
TI  - Studies on heterocycle-based pure estrogen antagonists.
AB  - 2-Phenylindoles and isosteric structures such as benzo[b]furans and
      benzo[b]thiophenes were used as estrogen receptor binding moiety for the
      syntheses of new nonsteroidal antiestrogens. The antiestrogenic potency was
      considerably enhanced following the introduction of polar functional groups into
      the side chain in position 1 (indole) or 3 (benzofuran, benzothiophene). The
      amino compounds could be characterized as mixed agonist/antagonists. Among the
      derivatives with an amide group compounds without any agonistic activity both in
      vitro and in vivo were identified. The amide function can be replaced by
      alkylthio or alkylsulfonyl groups without changing the endocrine profile very
      much. In this study, the estrogenic activity was determined in a new
      transcription assay with luciferase as the reporter. The results obtained in this
      assay were in very good agreement with those from the conventional mouse uterine
      weight test. Antitumor activity was determined in hormone-sensitive MCF-7 breast
      cancer cells. There was no difference in activity between partial and pure
      estrogen antagonists. However, the derivatives with sulfur containing side chains
      were much more active than the corresponding heterocycles with amino or carbamoyl
      functions. They reached IC50-values of about 1 nM. 2-Phenylindoles and 2
      phenylbenzothiophenes were rather similar in their potencies whereas the
      benzofuran derivatives were less active probably due to their lower binding
      affinities for the ER.

PMID- 7625719
TI  - Exploration of the therapeutic potential of the antiestrogen RU 58668 in breast
      cancer treatment.
AB  - The recently described pure antiestrogen RU 58668 displayed potent
      antiproliferative activities in vitro on several ER+ human mammary cell lines,
      stimulated either by estradiol or by endogenous or exogenous growth factors.
      Moreover, when administered to nude mice it proved to be the only antiestrogen to
      induce regression (at least 10 weeks) of estradiol-stimulated MCF-7 tumors,
      whereas tamoxifen only stabilized the tumor volume for 4 to 8 weeks. So the first
      purpose of this work was to study the effect of RU 58668 for 6 months and to
      evaluate its activity on tumors which escaped from the tamoxifen treatment. On
      the other hand, we looked for its effect on models more related to frequently
      described clinical observations, such as the overexpression of an oncogene or the
      implication of autocrine or paracrine growth factors. Long-term studies of RU
      58668 on the estradiol-stimulated MCF-7 model showed that this compound induced a
      shrinking of tumor volumes for at least 25 weeks (3 to 6 times longer than the
      stabilization induced by tamoxifen) and was able to reduce the volume of tumors
      which escaped from, or even were stimulated by, tamoxifen. On models of
      spontaneously growing tumors, where the overexpression of an oncogene or the
      production of growth factors was involved, RU 58668 induced the same tumor
      shrinking that was previously observed on estradiol- or tamoxifen-stimulated
      models. Finally, when MCF-7 cells were injected in the uteri, a spontaneous tumor
      take was observed (in about 80-90% of the animals), leading to a more than
      twofold increase in uterus weight. This growth is largely stimulated by estradiol
      and tamoxifen. On this model, histological examination showed that only 30% of
      the animals receiving RU 58668 displayed tumoral microfoci. These studies suggest
      that RU 58668 may be used for the treatment of ER+ patients which are primarily
      resistant to or which escaped from tamoxifen treatment. Its preventive activity
      on tumor take also suggests its use as an adjuvant to prevent the development of
      metastases.

PMID- 7625721
TI  - Pharmacological properties of a new selective antiprogestagen: Org 33628.
AB  - For antiprogestagens both selectivity (ratio of antiprogestational to
      antiglucocorticoid activity) and potency are important conditions for their
      applications in fertility regulation and correction of hormone-dependent
      irregularities. Org 33628 appears to fulfill both conditions most convincingly.
      The activities of this new antiprogestagen in various assays are compared with
      those of RU 38486 and a few other antiprogestagens. The binding of Org 33628 to
      the progesterone receptor is twice as high as that of RU 38486 whereas the
      binding to the glucocorticoid receptor is 25 times lower than that of RU 38486.
      The activity of Org 33628 in the pregnancy interruption test in rats is 16 times
      higher than that of RU 38486. The antiglucocorticoid activity of Org 33628 in
      rats is about eight times lower than that of RU 38486. In the ovulation
      inhibition test in rats Org 33628 is approximately 80 times more potent than RU
      38486. For menses induction in the stumptail monkey activity observed for Org
      33628 is only twice as high. IN CONCLUSION: Org 33628 is a very potent and
      selective antiprogestagen with a remarkably high ovulation-inhibitory activity.
      The magnitude of the potency difference with RU 38486 is species and/or target
      organ dependent.

PMID- 7625722
TI  - Mechanism of action of antiprogestins in the pregnant uterus.

PMID- 7625723
TI  - Differentiation therapy with progesterone antagonists.

PMID- 7625724
TI  - Clinical uses of mifepristone (MFP).

PMID- 7625725
TI  - Glucocorticoid antagonist RU 486 reverses agonist-induced apoptosis and c-myc
      repression in human leukemic CEM-C7 cells.
AB  - A synthetic glucocorticoid dexamethasone (DEX) inhibits proliferation and induces
      apoptosis of clone CEM-C7 cells, but not in clone CEM-C1 cells, even though they
      contain glucocorticoid receptors (GR). We previously showed that suppression of c
      myc is a critical step in glucocorticoid-induced cell lysis of C7 cells. It is
      not reduced in C1 cells. In this study we review the basis for this conclusion
      and present evidence that the glucocorticoid antagonist RU 486 rescues DEX
      treated C7 cells from cell death. An increase in DEX-repressed c-myc mRNA levels
      precedes the recovery of cell growth. A threshold level of Myc expression appears
      to be required to maintain growth and viability of C7 cells. Although C1 cells
      are highly resistant to lysis by glucocorticoids, addition of forskolin, an
      inducer of protein kinase A, synergizes to evoke complete apoptosis. This
      synergistic effect is prevented by RU 486, indicating direct involvement of the
      GR.

PMID- 7625726
TI  - The influence of antiglucocorticoids on stress and shock.

PMID- 7625727
TI  - Nuclear hormone receptors activate direct, inverted, and everted repeats.
AB  - Nuclear hormone receptors comprise a family of ligand-modulated transcription
      factors that link cellular responses to extracellular and intracellular signals.
      Receptors for retinoids, thyroid hormone, vitamin D3 and fatty acids/peroxisome
      proliferators bind their response elements as heterodimers with the retinoid X
      receptor. Naturally occurring response elements are composed of core-motifs that
      are organized as direct, inverted, and/or everted repeats. The structural
      mechanisms that facilitate binding of a single receptor heterodimer to such
      diverse binding sites remain unknown.

PMID- 7625728
TI  - The glucocorticoid receptor and RU 486 in man.
AB  - RU 486 is a prototype glucocorticoid antagonist with strong antiglucocorticoid
      activity in vitro and in vivo. Studies of its molecular mechanism of action have
      provided invaluable insights in the complex activation cascade of the GR itself.
      RU 486 effectively antagonizes glucocorticoids in most glucocorticoid-sensitive
      systems. Agonist effects, however, have been observed in some in vitro and in
      vivo systems, but remain the exception. In humans, administration of RU 486
      causes generalized glucocorticoid resistance with high levels of cortisol
      compensating for the peripheral receptor blockade. This state is similar to that
      of patients with generalized familial glucocorticoid resistance. Because of its
      HPA axis stimulatory effects, RU 486 has limited chronic utility as an
      antiglucocorticoid. To date, the application of RU 486 can only be recommended in
      inoperable patients with ectopic ACTH secretion or adrenal carcinoma who have
      failed to respond to other treatments. The unusually long half-life of this drug
      also poses problems with titrating its dose within a therapeutic range. The
      development of a short-acting, selective glucocorticoid antagonist is therefore,
      a desirable goal of future research.

PMID- 7625729
TI  - Drospirenone: a novel progestogen with antimineralocorticoid and antiandrogenic
      activity.
AB  - Drospirenone (ZK 30595; 6 beta, 7 beta, 15 beta, 16 beta-dimethylen-3-oxo-17
      alpha-pregn-4-ene-21, 17-carbolactone) is a novel progestogen under clinical
      development. Drospirenone is characterized by an innovative pharmacodynamic
      profile which is very closely related to that of progesterone. Potential
      applications include oral contraception, hormone replacement therapy and
      treatment of hormonal disorders. The pharmacological properties of drospirenone
      were investigated in vitro by receptor binding and transactivation experiments
      and in vivo in appropriate animal models. In qualitative agreement with
      progesterone, the compound binds strongly to the progesterone and the
      mineralocorticoid receptor and with lower affinity to androgen and glucocorticoid
      receptors. There is no detectable binding to the estrogen receptor. Steroid
      hormone agonistic and antagonistic activities of progesterone and drospirenone
      were compared in transactivation experiments. Individual steroid hormone
      receptors were artificially expressed together with a reporter gene in
      appropriate cell lines. Both hormones were unable to induce any androgen receptor
      mediated agonistic activity. Rather, both progesterone and drospirenone
      distinctly antagonized androgen-stimulated transcriptional activation. Likewise,
      both compounds only very weakly activated the mineralocorticoid receptor but
      showed potent aldosterone antagonistic activity. Drospirenone did not induce
      glucocorticoid receptor-driven transactivation. Progesterone was a weak agonist
      in this respect. Drospirenone exerts potent progestogenic and antigonadotropic
      activity which was studied in various animal species. It efficiently promotes the
      maintenance of pregnancy in ovariectomized rats, inhibits ovulation in rats and
      mice and stimulates endometrial transformation in the rabbit. Furthermore,
      drospirenone shows potent antigonadotropic, i.e., testosterone-lowering activity
      in male cynomolgus monkeys. The progestogenic potency of drospirenone was found
      to be in the range of that of norethisterone acetate. The majority of clinically
      used progestogens are androgenic. Drospirenone, like progesterone, has no
      androgenic but rather an antiandrogenic effect. This property was demonstrated in
      castrated, testosterone propionate substituted male rats by a dose-dependent
      inhibition of accessory sex organ growth (seminal vesicles, prostate). In this
      model, the potency of drospirenone was about a third that of cyproterone acetate.
      Drospirenone, like progesterone, shows antimineralocorticoid activity, which
      causes moderately increased sodium and water excretion. This is an outstanding
      characteristic which has not been described for any other synthetic progestogen
      before. Drospirenone is eight to ten times more effective in this respect than
      spironolactone. The natriuretic effect was demonstrable for at least three weeks
      upon daily treatment of rats with a dose of 10 mg/animal. Drospirenone is devoid
      of any estrogenic, glucocorticoid or antiglucocorticoid activity. In summary,
      drospirenone, like progesterone, combines potent progestogenic with
      antimineralocorticoid and antiandrogenic activity in a similar dose
      range.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7625730
TI  - Effects of forskolin on steroid receptors.

PMID- 7625731
TI  - Molecular mechanism of inhibition of steroid dehydrogenases by licorice-derived
      steroid analogs in modulation of steroid receptor function.

PMID- 7625732
TI  - Biochemical significance of the 6-s-cis conformation of the steroid hormone 1
      alpha,25-dihydroxyvitamin D3 based on the provitamin D skeleton.

PMID- 7625733
TI  - Effects of a new vitamin D analog, EB 1089, on osteoblastic cells.

PMID- 7625734
TI  - Effects of androgens and antiandrogens on the conformation of the androgen
      receptor.

PMID- 7625736
TI  - Inhibition of nuclear transport is not essential for inhibition of receptor
      function by the type II estrogen antagonist ICI-164,384.

PMID- 7625737
TI  - Mood disorder in women with early breast cancer taking tamoxifen, an estradiol
      receptor antagonist. An expected or unexpected effect?

PMID- 7625738
TI  - Diethylstilbestrol (DES)-related endocrine disturbances in women. A story with no
      end, yet.

PMID- 7625735
TI  - Raloxifene is a tissue-selective agonist/antagonist that functions through the
      estrogen receptor.

PMID- 7625739
TI  - Estrogen/antiestrogen responsiveness in an in vivo/in vitro model for myometrial
      tumorigenesis.

PMID- 7625740
TI  - Vascular endothelial growth factor (VEGF) in primate endometrium.
      Immunohistochemical patterns during the cycle and after chronic RU 486 treatment
      in cynomolgus monkeys.

PMID- 7625742
TI  - Synthesis and biological activity of novel nonsteroidal progesterone receptor
      antagonists.

PMID- 7625741
TI  - Ubiquitous receptor: structures, immunocytochemical localization, and modulation
      of gene activation by receptors for retinoic acids and thyroid hormones.

PMID- 7625743
TI  - Glucocorticoid receptors in mouse melanoma cells.

PMID- 7625744
TI  - The effects of glucocorticoid receptor (GR) blockade by RU 38486 and GR
      protection by GTT on hemorrhagic shock in rats.

PMID- 7625745
TI  - Anabolic steroids induce skeletal muscle injury and immediate early gene
      expression through a receptor-independent mechanism.

PMID- 7625746
TI  - Commonly used therapeutic doses of glucocorticoids impair explicit memory.

PMID- 7625748
TI  - Dexamethasone downregulates mineralocorticoid receptors in A6 amphibian kidney
      cells in tissue culture.

PMID- 7625747
TI  - Point mutations in the 90-kDa heat shock protein binding region of the
      glucocorticoid receptor affect the functional characteristics of the receptor.

PMID- 7625749
TI  - General structure-activity correlations of antihormones.

PMID- 7625750
TI  - Connection between immunosuppressants and steroids via HSP90.

PMID- 7625751
TI  - Local inhibition of sebaceous gland growth by topically applied RU 58841.
AB  - The biological activity of a series of nonsteroidal, pure androgen receptor
      inhibitors was compared using the Syrian hamster ear skin sebaceous gland model.
      RU 58841, RU 56187, RU 38882 and cyproterone acetate were applied topically for 4
      weeks on the ventral ear pinna of sexually mature male Syrian hamsters. Their
      order of efficacy was as follows: RU 58841 > RU 56187 > RU 38882 > cyproterone
      acetate. Maximal reduction of 60% in the size of the sebaceous glands was
      observed in hamsters treated with RU 58841 at a dose of 10 micrograms per day.
      This degree of inhibition occurred without any systemic side effects as shown by
      the absence of inhibition on the contralateral untreated ear pinna. Longer
      treatment did not produce greater inhibition since extending the treatment period
      from 4 weeks to 12 weeks showed similar data. The effect of RU 58841 was
      reversible since the inhibited sebaceous glands returned to normal size within 4
      weeks after the cessation of the topical applications. The potent localized
      inhibition of sebaceous glands by RU 58841 demonstrates the excellent potential
      of this compound as a topical drug for the treatment of acne and other androgen
      mediated disorders.

PMID- 7625752
TI  - Casodex: preclinical studies and controversies.

PMID- 7625754
TI  - No evidence for genomic imprinting in liveborn Down syndrome patients.
AB  - Despite numerous studies, the clinical heterogeneity of Down syndrome has no
      explanation. The authors have attempted to investigate the role of genomic
      imprinting in the phenotype of liveborn Down syndrome patients. Hundred fifty
      eight patients were investigated for parental origin of the extra chromosome 21
      with standard cytogenetic analyses and with DNA polymorphic markers. The extra
      chromosome 21 was of paternal origin in 8 cases and of maternal origin in 150
      cases. The phenotype of Down syndrome patients in whom the nondisjunction was of
      maternal origin, was not different from the phenotype of Down syndrome patients
      in whom the nondisjunction was of paternal origin. The authors conclude that
      imprinting may probably not play a role in the heterogeneity of Down syndrome
      phenotype.

PMID- 7625753
TI  - Regulation of androgen action by receptor gene inhibition.
AB  - Regulated functions of hormonal agents play a critical role in health and
      disease. Target cell responsiveness to a hormonal signal is a product of both
      cellular concentrations of the hormone ligand and the corresponding receptor
      protein. The major thrust of the drug design for treatment of endocrine-related
      problems, so far, has been directed to ligand derivatives. In certain cases,
      receptor regulation through antigene technology has much to offer with
      improvements in both target cell and hormonal specificity. Three different
      antigene approaches are currently being explored. The first approach is to
      inhibit the expression of the receptor gene by disrupting the DNA protein
      interaction at critical cis-elements by short triple helix-forming
      oligonucleotides. The second approach is to sequester and inactivate the receptor
      mRNA by the antisense mRNA produced in the target tissue directed by a
      heterologous tissue-specific promoter. The third approach is the tissue-specific
      expression of a catalytic ribozyme that binds to the specific receptor mRNA and
      selectively degrades it before its translation into the protein. In this study,
      we have characterized the promoter of the rat androgen receptor, and by
      progressive deletion from its 5' end have identified two critical cis-regulatory
      elements, one at the -960 to -940 region and the other at the -554 to -574
      positions. The former is an activator while the latter is an inhibitor domain.
      The inhibitory domain is the binding site for the nuclear factor kappa B (NF
      kappa B) and more specifically, the p50/p50 homodimer of this transcription
      factor family. We have also provided correlative data to show that under normal
      physiological conditions, the NF-kappa B functions as an antiandrogen during the
      age-dependent desensitization of the liver. In addition to the naturally
      functioning antiandrogenic influence of NF-kappa B, we have designed an
      artificial antiandrogenic agent, a triplex-forming oligonucleotide (TFO) directed
      to the -960/-940 activator domain of the rat androgen receptor gene promoter.
      This oligonucleotide at a TFO-to-promoter ratio of 500 is able to cause about 60%
      inhibition of rAR promoter function in transfected COS-1 cells. These results
      clearly demonstrate the feasibility of the antigene approach for effective
      inhibition of steroid hormone action.

PMID- 7625755
TI  - Genetic counselling in breast cancer: sensitivity to parameter values and to
      available information.
AB  - Most segregation analyses have concluded that breast cancer results from a
      mixture of sporadic and genetic cases. Genetic cases are probably due to a rare
      inherited mutation with autosomal dominant transmission. The lifetime risk for
      female mutation carriers is close to 1, ten fold greater than for noncarriers.
      Beyond these accepted results, studies differ in the estimated parameters
      specifying the correspondence between phenotypes and genotypes. We show here that
      these differences have an impact on the estimation of the probability that a
      woman is carrying a mutation given her disease status and also given the
      information on the disease status of her family members. We illustrate this
      problem by computing the probability of being a mutation carrier for 16 women (9
      affected, 7 unaffected) belonging to one pedigree, using three sets of parameter
      values. For two of the women, the probability that they inherited the mutation is
      low, but it varies considerably according to the set of parameter values. For one
      woman, the probability varies from 20 to 60% if familial information is taken
      into account. Segregation of 17q markers in families may provide additional
      information depending on the posterior probability of linkage. Indeed in the
      pedigree studied here, the segregation of 17q markers provided additional
      information which moreover decreased the sensitivity to the parameters values.
      However, the decrease in sensitivity will only be observed if the posterior
      probability of linkage of the family to the studied markers is high.

PMID- 7625756
TI  - A new hybrid cell line containing only human chromosome 15 selected through
      fluorescence in situ hybridization and characterized by Alu-PCR amplification of
      the human DNA.
AB  - Human Cot1 DNA directly labeled with dUTP-fluorochromes (FITC, Rhodamin) and used
      as a probe, allowed rapid detection of one or a few human chromosomes in human
      hamster hybrid cells by in situ hybridization (FISH). A hybrid cell line
      containing only a human acrocentric chromosome was isolated (CH35B2D). The DNA
      from this hybrid was used for PCR amplification with a single Alu (A33) primer.
      After agarose gel electrophoresis, a continuum of intense bands of between 400
      700 bp was observed with A33-PCR products. No amplified product was visible with
      hamster DNA. FISH on normal human metaphases of biotinylated Alu-PCR products
      obtained with Alu A33 and competition with human Cot1 DNA showed decoration, with
      high specificity for chromosome 15. It was identified after R banding obtained
      with PI or DAPI in an antifade adjusted to pH11 with NaOH. Under the applied
      conditions, the Alu (A33) products are expected to be useful for
      characterization, by specific decoration of chromosome 15 aberrations in
      pathological cells. CH35B2D could be employed for functional studies of genes
      located on chromosome 15.

PMID- 7625757
TI  - Distribution of single organ malformations in European populations. EUROCAT
      Working Group.
AB  - The aim of this study was to evaluate the prevalence of congenital anomalies in
      19 areas from 13 European countries. A total of 291,126 births were surveyed. On
      average most of the anomalies were recorded in livebirths. The total prevalence
      of congenital anomalies was 21.8 per 10,000 births. Four groups of congenital
      anomalies were of particular note in the consideration of geographic variations:
      neural tube defects, cleft lip, limb reduction defect and Down syndrome. For
      neural tube defects, 24 cases per 10,000 were recorded in the British Isles
      whereas only 9.6 cases per 10,000 were registered in Continental Europe. Cleft
      lip had a much higher prevalence in Groningen (The Netherlands) and in Odense
      (Denmark) than in the other European countries under study. The prevalence of
      limb reduction defect was high in Bilbao (Spain), in Odense, in Strasbourg
      (France) and in Groningen. In the study population the prevalence of Down
      syndrome ranged from 5.6 to 21.3 per 10,000 livebirths.

PMID- 7625758
TI  - Renal agenesis and trisomy 22: case report and review.
AB  - Renal agenesis has been reported in the literature in a wide variety of
      chromosomal abnormalities. Trisomy 22 is frequently seen in first trimester
      miscarriages but is extremely rare in life-borns. The authors report on a second
      trimester female foetus with oligohydramnios sequence secondary to bilateral
      renal agenesis and trisomy 22 and review the literature.

PMID- 7625759
TI  - Prevalence of neural tube defects in northeastern France, 1979-1992 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 1979-1992 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 1979-1992 was
      10.94 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 and 50 per cent for spina bifida and
      encephalocele, respectively. This decrease 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- 7625760
TI  - [Chromosome microdissection: applications and prospects].
AB  - A new microdissection and microcloning procedure of human banded chromosomes has
      been described. These micro-techniques allow the construction of band-specific
      DNA libraries, providing a large number of DNA probes for the identification of
      gene sequences. These technologies associated with fluorescence in situ
      hybridization studies are particularly efficient to analyse chromosomal regions
      involved in human genetic diseases including cancer.

PMID- 7625761
TI  - Tetrasomy 9p syndrome.

PMID- 7625762
TI  - Molecular analysis of the third allele of human deoxyribonuclease I polymorphism.
AB  - In addition to common phenotypes 1, 1-2 and 2 of human deoxyribonuclease I (DNase
      I), phenotypes 1-3 and 2-3, encoded by a third allele DNASE1*3, have been found
      by means of isoelectric focusing. The main objective of this study was to
      identify the mutation site(s) underlying phenotype 3. All eight exons covering
      the entire open reading frame of the human DNase I structural gene were amplified
      by the polymerase chain reaction (PCR) and subjected to direct DNA sequencing.
      When the entire 780-bp coding region and exon/intron junctions of the DNase I
      gene of two individuals with phenotypes 1-3 and 2-3 were sequenced, only one
      nucleotide substitution, a C-G transition (CCC-->GCC), in the codon for amino
      acid 132 of the mature enzyme located in exon VI was found that resulted in the
      replacement of proline with alanine (P132A). The mutation was confirmed by allele
      specific amplification of genomic DNA. The replacement of the amino acid residue
      may reduce the hydrophobicity of the enzyme and thus increase the pI value of the
      type-3 isozyme compared with that of type 1, as increasing the hydrophobicity of
      a protein is known to decrease its pI value. The specific PCR-amplifications of
      exons and alleles developed in this study may provide a new tool suitable for
      rapid screening of DNase I variants.

PMID- 7625763
TI  - Molecular variation of the human elastin (ELN) gene in a normal human population.
AB  - DNA sequence diversity in the human elastin genomic region has been estimated by
      RFLP analysis in a normal human population. The proportion of polymorphic
      nucleotides and the degree of nucleotide diversity were 0.0034 and 0.0018
      respectively. It is argued that the estimate of nucleotide diversity does not
      indicate strong purifying selection in the region. A total of 144 restriction
      sites were sampled in each of 80 independent chromosomes representing the
      screening of 58080 bp overall. Six main haplotypes were constructed; they
      represent at least 84% of the 80 chromosomes sampled. Analysis for linkage
      disequilibrium revealed two statistically significant comparisons out of 54
      tests, approximately the proportion that would be statistically significant at
      the 5% level by chance. A higher order quadrigenic disequilibrium was detected.
      The relationship between the physical distance separating polymorphic restriction
      sites and linkage disequilibrium is discussed. The development of elastin
      haplotypes and knowledge of the pattern of linkage disequilibrium should aid the
      study of elastin related disease and human evolution.

PMID- 7625764
TI  - DNA polymorphisms of the complement C6 and C7 genes.
AB  - The linked C6 and C7 loci are rich in genetic markers, both at the protein and
      DNA levels. There are now seven common DNA polymorphisms distributed over about
      300 kbp of chromosome 5p12-14. We report a new TaqI RFLP for C7 and a method for
      typing a C7 variant (T368S) hitherto known only from cDNA clones. We have re
      investigated the published RFLPs to provide information on their frequency in
      North European Caucasian (predominantly British and Irish) subjects and have
      revised some of the published parameters, especially the sizes of polymorphic
      restriction fragments. Their precise locations within the genes are also
      reported: the three markers for C6 are in exon 3, intron 3 and adjacent to exon
      17 and the four markers for C7 are in introns 15 and 13 and in exons 13 and 9.
      The gene frequencies of the second commonest allele of all seven markers lie in
      the range 0.2 to 0.37, except C6 A/B in the Japanese, where the frequencies of
      both common alleles are about 0.45. We have estimated the gene frequencies for
      the DNA polymorphisms which correlate with C7 M/N phenotype and for the C6 A/B
      phenotype and find them to be the same as the phenotypic estimates in Caucasians
      and in the Japanese respectively. The markers provide the possibility of defining
      128 haplotypes, many (28) of which have been observed. Allelic associations in
      these genes are generally surprisingly weak.

PMID- 7625765
TI  - Complement component C6 and C7 haplotypes associated with deficiencies of C6.
AB  - Both complete C6-deficiency (C6*Q0) and subtotal C6-deficiency (C6*SD) have been
      described as simple recessive traits and C6*SD has been described in combination
      with subtotal deficiency of the C7 coded at an adjacent locus. The trace of C6
      protein found in both C6*SD traits is phenotypically indistinguishable, being
      smaller than normal C6 and having different isoelectric properties. A defect has
      been found in the C6 gene which plausibly explains the C6*SD phenotype, and this
      defect is also common to both C6*SD traits. We present data from seven DNA
      markers of the C6 and C7 genes which show that although at least four haplotypes
      are associated with C6*Q0, most South African C6*Q0 patients carry a common
      defective haplotype. The most common haplotype associated with C6*Q0 has been
      observed only once among unaffected haplotypes of relatives. In one family, the
      cases of C6*SD share a complete haplotype with both cases of combined deficiency
      and are probably heterozygous for this condition and complete deficiency of C6.
      In another family, the C6*SD is on a slightly different haplotype and C7 is
      normally expressed. Thus, the C6 defect is not sufficient on its own to explain
      the C7 deficiency in the combined deficient haplotype. The haplotype associated
      with the combined deficiency is found not only in normal control subjects, but
      also in one case of complete C6 deficiency. In this case the molecular defect
      seen in combined or C6*SD cases is absent.

PMID- 7625766
TI  - Apolipoprotein E polymorphism in Italy investigated in native plasma by a simple
      polyacrylamide gel isoelectric focusing technique. Comparison with frequency data
      of other European populations.
AB  - A new polyacrylamide gel isoelectric focusing (PAGIEF) technique has been
      developed that allows rapid and reliable identification of Apolipoprotein E
      (APOE) phenotypes directly from plasma or serum without any prior treatment. This
      method was used to determine the APOE phenotypes in samples from Central and
      Southern Italy, Sicily, and Sardinia. The frequencies observed for the APOE*2,
      APOE*3, and APOE*4 alleles in Central and Southern Italy (Sicily included) were
      similar (0.066, 0.851, 0.083 and 0.056, 0.858, 0.085 respectively) though lower
      APOE*4 frequencies were found in the more southern regions. The Sardinian
      population showed APOE gene frequencies (APOE*2 = 0.050, APOE*3 = 0.898, APOE*4 =
      0.052) to be significantly different from those of the rest of Italy owing to the
      low APOE*4 frequency, the lowest among Caucasian populations. The frequencies
      were compared with those found in other European populations. A clear cut North
      South decreasing cline was found for APOE*4 allele frequencies and an opposite
      trend was found for APOE*3 frequencies. The overall dispersion of European
      populations as determined by the three APOE allele frequencies was graphically
      represented using coordinate analysis. The tendency of the APOE*4 frequency to
      decline with latitude both at the Italian and at the European level was discussed
      with reference to similar trends observed for dietary habits (saturated fat
      intake).

PMID- 7625767
TI  - Cladistic analysis of the apolipoprotein AI-CIII-AIV gene cluster using a healthy
      French Canadian sample. I. Haploid analysis.
AB  - A cladistic analysis was carried out to identify haplotypes hypothesized to
      differ for functional DNA sequence variations within the apolipoprotein (apo) AI
      CIII-AIV gene cluster that affect plasma lipid, lipoprotein and apolipoprotein
      levels. A sample of unrelated healthy French Canadians was studied. First, a
      cladogram of the observed apo AI-CIII-AIV haplotypes was estimated. Then this
      cladogram was used to define a statistical analysis of the association between
      haplotype variation and variation in plasma lipid, lipoprotein and apolipoprotein
      levels. Three haplotypes were identified which were associated with small (5-12%
      of the total sum of squares) pleiotropic effects on plasma lipid, lipoprotein and
      apolipoprotein traits and these effects were context, i.e. gender, dependent.

PMID- 7625768
TI  - Development of a panel of monochromosomal somatic cell hybrids for rapid gene
      mapping.
AB  - We have assembled a panel of monochromosomal somatic cell hybrids for use in gene
      mapping. DNA from each individual hybrid was used as a probe on normal human
      metaphases to identify the human chromosome and any fragments by reverse
      painting. To test the efficiency of the panel PCR amplification of DNA from the
      monochromosomal somatic cell hybrid panel was used in combination with human
      specific oligonucleotide primers to assign alpha-catenin (CTNNA1) and p21/WAF1 to
      chromosomes 5 and 6 respectively. These genes were localized further using
      hybrids containing specific translocations to 5q11-qter and 6p21 respectively. We
      also developed primers to enable us to assign 17 ESTs sequenced by the HGMP
      Resource Centre. The hybrid panel was developed with support of the UK HGMP and
      the DNA is available to all registered users.

PMID- 7625769
TI  - What stabilizes the sex ratio?
AB  - It is suggested that the human sex ratio at birth is stabilized only to a minor
      extent by the direct processes of natural selection. Instead the major factors
      stabilizing sex ratio seem to be behavioural (coital rates) and psychological
      (parental perceptions of adult sex ratios). It is suggested that parental hormone
      levels are (a) a consequence of perceived adult sex ratios, and (b) a cause of
      sex ratio in the next generation, thus providing the basis for a negative
      feedback process stabilizing the sex ratio.

PMID- 7625770
TI  - Broiler chick responses to anorectic agents: dietary acetic and propionic acids
      and the blood metabolites.
AB  - The effects of dietary supplementation with acetic or propionic acid, given at a
      level of 3% of diets containing 2,500 or 2,750 kcal of metabolizable energy per
      kg, on levels of blood glucose, and on lipid, protein, and energy metabolisms
      were studied in female broiler chicks. Voluntary feed and energy intakes, as well
      as body weight gain, decreased significantly with the inclusion of the acids in
      either diet, in decreasing order of effect: propionate > acetate >
      nonsupplemented controls. The relative weight of the abdominal adipose tissue
      decreased significantly with the inclusion of either acid, but was unaffected by
      dietary energy level. In contrast, the weight of the liver was higher in birds
      fed the low-energy diet, but was unaffected by the anorectic agents. Inclusion of
      the acids increased the concentration of volatile fatty acids in the cecum and
      blood plasma. The rate of clearance of plasma propionate was greater than that of
      acetate. Anorectic agents and dietary energy density exhibited a synergistic
      effect on feed intake. These agents altered blood metabolites involved in lipid
      and energy metabolisms, but not in that of protein. Plasma metabolites and
      enzymes, particularly beta-hydroxybutyrate and alkaline phosphatase, reflected
      the degree of feed restriction, supporting the hypothesis that the hypophagic
      effect of these acids is due to metabolic intervention.

PMID- 7625771
TI  - Comparison of recovery of previously depressed hepatic delta 6 desaturase
      activity in adult and old rats.
AB  - The ability to recover hepatic delta 6 desaturase (delta 6D) activity with
      linoleic acid as substrate was compared in adult and old rats. Male rats fed a
      diet deficient in alpha-linolenic acid were used either at 6 or 21 months. From
      these two ages onward, animals were fed a diet containing 10% fish oil for 3
      months to reduce delta 6D activity. After this period, some of the animals were
      killed. The other animals were returned to the original diet deficient in alpha
      linolenic acid. Fatty acid composition in liver and brain and hepatic delta 6D
      activity were analysed 3 and 7 days after the change in diet. When rats were fed
      the diet containing 10% fish oil, delta 6D activity was lower than in those fed
      the diet deficient in alpha-linolenic acid. The liver fatty acid composition was
      altered with disappearance of 22:5 n-6 and a decrease in 18:2 n-6, 20:4 n-6 and
      22:4 n-6 accompanied by an increase in 20:5 n-3, 22:5 n-3 and 22:6 n-3. When rats
      were re-fed the original diet, delta 6D activity returned after 3 days to its
      initial level in the 9-month-old rats; in 24-month-old animals, recuperation was
      incomplete. The level of 20:4 n-6 and 18:2 n-6 increased in the liver
      concurrently with a decrease in levels of 20:5 n-3, 22:5 n-3 and 22:6 n-3. In
      both age groups, the brain fatty acid profile remained unchanged 7 days after
      returning to the diet deficient in alpha-linolenic acid.

PMID- 7625772
TI  - Risk and benefit of low fat intake in childhood.
AB  - The consumption of a low-fat diet is advocated as beneficial in the prevention of
      cardiovascular disease. Because of still existing controversy the hypothesis
      whether low fat intake < or = 30% of total calories can maintain optimal growth
      and supply the desirable quantity of micronutrients was tested in a cohort of 500
      children in preschool age. The children, apparently in good health and without
      any special dietary regimen, were stratified according to fat intake in three
      groups: < 30, 30-40 and > or = 40% of calories provided by fat. Our findings
      indicate that children with low fat intake were at a quite important risk of
      unsatisfactory intakes of fat-soluble vitamins, and also the nutritional density
      of consumed food was lower. The proportions of saturated (SFA), polyunsaturated
      and monounsaturated fatty acids were rather similar in all three groups, but
      cholesterol and SFA intakes decreased significantly in those with low fat intake.
      Serum cholesterol and triglyceride levels were however not significantly
      influenced.

PMID- 7625773
TI  - Effect of acute glycerol administration with or without a mixed meal in humans.
AB  - We explored the effects of oral glycerol administration (20 g) alone or in
      combination with a mixed meal on postprandial lipids, free fatty acids, high
      density lipoprotein cholesterol and retinyl palmitate. We also tested the meal
      alone as a control. The metabolic behavior of 13C-labelled glycerol, mainly its
      incorporation into triglycerides and glucose, was also investigated. The tests
      were performed on 13 healthy subjects aged 20-56 years (mean 32.1 +/- 10.8).
      Glycerol administration alone induced a decrease in plasma free fatty acid
      levels. When glycerol was given with the meal, it was absorbed faster and
      postprandial triglyceride levels were higher compared to the meal alone (p <
      0.05). An earlier and higher peak of retinyl palmitate was also observed when
      comparing the glycerol and mixed meal test to the mixed meal alone. No
      significant effect was observed on total, high-density and low-density
      lipoprotein cholesterol. These results suggest that the glycerol-induced increase
      in postprandial triglyceride levels is probably due to an increase in chylomicron
      synthesis and perhaps to the stimulation of intestinal glycerol kinase activity.
      13C-labelled glycerol administration showed a more important glycerol
      incorporation in lipoproteins with a density range of < 1.006 during the test
      with glycerol alone as compared to the test with glycerol and a mixed meal,
      suggesting that the rate of glycerol incorporation into lipoproteins depends on
      the availability of other substrates.

PMID- 7625774
TI  - Calculated iodine intake before and after simulated iodization (Dutch Nutrition
      Surveillance System).
AB  - To estimate the effect of possible goitre prophylactic measures on the intake of
      iodine among population groups, simulation studies, based on the first Dutch
      National Food Consumption Survey, were carried out. Iodine intake figures and
      prevalence of low intakes were calculated after fictively iodizing either bread,
      a combination of industrial products, milk and dairy products (without cheese) or
      margarine and shortenings. In addition, the effect of iodizing both bread and
      cheese or bread + biscuits + rusks was calculated. The simulated iodization of
      different products increased mean calculated iodine intakes by up to 45% and gave
      a reduction of 60-90% in the prevalence of iodine intakes below 100
      micrograms/day. The maximum acceptable intake of 1 mg iodine per day was never
      reached by any subject (average of 2 days). It is concluded that it is possible
      to increase substantially the mean iodine intake of the Dutch population and to
      decrease the prevalence of low iodine intakes without a clear risk of exceeding
      the maximum acceptable daily oral iodine intake.

PMID- 7625775
TI  - Effect of vitamin D repletion on testicular function in vitamin D-deficient rats.
AB  - Freshly weaned 30-day-old male Wistar rats were fed a vitamin D-deficient diet
      adequate in calcium and phosphorus for 3 months. On the 120th day of age three
      different doses of vitamin D were injected intramuscularly into three groups of
      rats and maintained for another month with water and a normal diet ad libitum.
      One group was continued with a vitamin D-deficient diet up to the 150th day. One
      group of animals was killed by decapitation on the 120th day and testicular
      functions like sperm count in testis and epididymis, testicular glutamyl
      transpeptidase activity and Leydig cell count as well as body weight were noted.
      On the 150th day animals of all groups were killed and testicular function was
      studied. Body weight and testicular function decreased significantly on the 120th
      and 150th day of age in vitamin D-deficient rats as compared to age-matched
      normal control rats. Injection of lower doses of vitamin D on the 120th day of
      age improved testicular function after 1 month whereas administration of a high
      dose of vitamin D caused a deterioration of the testicular function. The result
      suggests that retardation of spermatogenesis due to disturbances in Sertoli and
      Leydig cell function in vitamin D deficiency is reversible and can be corrected
      by supplementing an optimal dose of vitamin D.

PMID- 7625776
TI  - Effect of dietary antioxidants on the susceptibility to hepatic microsomal lipid
      peroxidation in the rat.
AB  - The inhibitory effect of probucol on ferrous-iron-induced microsomal lipid
      peroxidation was compared to that of alpha-tocopherol and butylated
      hydroxytoluene (BHT). Male Wistar rats were fed with diets containing 1%
      probucol, 0.2% BHT or 0.1% alpha-tocopherol for 30 days. There were no effects of
      dietary antioxidants on growth parameters, although liver weight was
      significantly higher in the BHT-fed rats. Probucol reduced serum levels of total
      and free cholesterol, while BHT feeding increased the concentrations of serum
      thiobarbituric-acid-reactive substances, HDL cholesterol and hepatic
      phospholipid. alpha-Tocopherol had no effect on these parameters. Incorporation
      of both, probucol and alpha-tocopherol, decreased the susceptibility of
      microsomes to lipid peroxidation in vitro, while BHT incorporation increased
      hepatic microsomal lipid peroxidation. These results suggest the possible
      usefulness of probucol for treatment of both hypercholesterolemia and elevated
      hepatic microsomal lipid peroxidation, while alpha-tocopherol decreases only an
      elevated lipid peroxidation. BHT works as a prooxidant.

PMID- 7625777
TI  - The politics of caring: the role of activism in primary care.
AB  - The role of activism in primary care practice, inquiry, and theory development is
      illustrated through the description of a feminist cooperative inquiry group's
      deconstruction of menarche education. The development of the emancipatory inquiry
      method of activist nursing inquiry and its relationship with feminist process is
      described. The value of feminist process in activist primary care inquiry and
      practice is examined. A theory of primary caring is inductively gleaned from the
      research and compared to other caring theories. Connection, commitment,
      consistency, change, and community are identified as being components of primary
      caring. A community perspective on primary care is advocated.

PMID- 7625778
TI  - Rethinking primary care: connections to nursing.
AB  - Although the fundamental values of primary care are congruent with basic values
      of nursing, nursing practice in the context of primary care is not always
      conceptualized as nursing. This article explores themes of primary care and
      nursing and offers a reconceptualization of primary care as nursing. An example
      of primary care as nursing practiced in a Philippine village is presented.

PMID- 7625779
TI  - Teenage mothers' narratives of self: an examination of risking the future.
AB  - The conventional wisdom that teenage mothering risks the future disregards the
      fact that the young mother's experience and understanding of her past as well as
      her anticipation of the future are intimately tied to the social world she
      inhabits. To recovery the contextual and temporal nature of teenage mothers'
      lives, this interpretive-phenomenological study explored young mothers' self
      understandings of identity and the life course as participants and members of
      families and communities. Implications of interpretive findings for a narrative
      conception of identity and the life course are described and applied to community
      based, community-focused primary health care.

PMID- 7625780
TI  - Cultural beliefs and health behaviors of pregnant Mexican-American women:
      implications for primary care.
AB  - A significant aspect of holistic primary care nursing is that it seeks to assess
      and understand clients' health beliefs and behaviors in the context of culture.
      This article examines implications for primary care nursing practice based on the
      cultural beliefs and health behaviors of pregnant Mexican-American women. Giger
      and Davidhizar's transcultural assessment model is used to evaluate six cultural
      phenomena present in all cultural groups. Culturally sensitive primary care by
      certified nurse-midwives in a community health birth center setting is described.

PMID- 7625781
TI  - The alienation of the sufferer.
AB  - Suffering is a particularly human experience that often brings with it loneliness
      or alienation from others. The theory described in this article explains the
      mechanisms through which suffering affects an individual's sense of community and
      connectedness with others. The intricate patterns are explained to provide a
      basis for prescriptive nursing to prevent or reverse this loss of connectedness.
      First, the article develops the concept of suffering and its influences on
      relationship with the self and with others and the relationship of others with
      the sufferer. Then, the concept of alienation is developed in this context, its
      philosophical roots explored, and a continuum described that encompasses
      alienation through connectedness. Related concepts of separation, shame, and
      stigma are briefly described as partial cases of alienation of the sufferer that
      also show the pervasiveness of the phenomenon. Next, the personal characteristics
      of an individual who might help are developed through the concept of wisdom.
      Last, an explanation is given as to why care is the contextual framework through
      which alienation is reversed and connectedness achieved. Although suffering,
      alienation, and care have gone by many names, the essences of these phenomena
      have been recurrent theme in descriptions of human response.

PMID- 7625782
TI  - Patterns of knowing: review, critique, and update.
AB  - Carper's patterns of knowing in nursing have been consistently cited in the
      nursing literature since they appeared in 1978. The degree to which they
      represent nursing knowledge in the mid-1990s is explored, and a major
      modification is suggested--the addition of a fifth pattern, sociopolitical
      knowing. The article also suggests modifications to the model for nursing
      knowledge put forward by Jacobs-Kramer and Chinn to enable this model to be used
      more effectively as a framework for exploring processes of inquiry into nursing
      knowledge and practice.

PMID- 7625784
TI  - In vitro and in vivo antibacterial activities of BO-2727, a new carbapenem.
AB  - BO-2727, a new injectable carbapenem, was evaluated for its in vitro and in vivo
      antibacterial activities in comparison with those of biapenem, meropenem,
      imipenem, cefpirome, and ceftazidime. BO-2727 had activity comparable to that of
      imipenem against methicillin-susceptible staphylococci and streptococci, with
      MICs at which 90% of strains tested (MIC90s) are inhibited being equal to 0.5
      microgram/ml or less. Against methicillin-resistant staphylococci, BO-2727 was
      the most active among the antibiotics tested, with MIC90s ranging from 4 to 8
      micrograms/ml. BO-2727 was highly active against members of the family
      Enterobacteriaceae, Haemophilus influenzae, and Moraxella catarrhalis, with
      MIC90s ranging from 0.006 to 2 micrograms/ml. BO-2727 was also highly active
      against Pseudomonas aeruginosa (imipenem-susceptible strains), for which the
      MIC90 was 2 micrograms/ml, which was lower than those of imipenem, cefpirome, and
      ceftazidime and comparable to those of biapenem and meropenem. Differences in
      activity between BO-2727 and the other carbapenems against imipenem-resistant P.
      aeruginosa were particularly striking (MIC90, 8 micrograms/ml). Furthermore, BO
      2727 displayed a high degree of activity against many of the ceftazidime-,
      ciprofloxacin-, and/or gentamicin-resistant isolates of P. aeruginosa. The in
      vivo efficacy of BO-2727 against experimental septicemia caused by gram-positive
      and gram-negative bacteria, including methicillin-resistant Staphylococcus aureus
      and imipenem-resistant P. aeruginosa, reflected its potent in vitro activity and
      high levels in plasma.

PMID- 7625783
TI  - Antiviral activities of isometric dideoxynucleosides of D- and L-related
      stereochemistry.
AB  - In summary, many isomeric analogs of ddNs of both D-related and L-related
      absolute stereochemistries have been synthesized and evaluated in vitro for their
      antiviral activities. A few of these compounds exhibit potent antiviral activity
      and, interestingly, belong to both the D and L families. The synthetic
      methodologies developed will allow accessibility to many more novel modified
      nucleosides. While some structure-activity relationships are emerging from this
      work, it is clear that these chiral isomeric nucleosides have opened a new
      chapter in the field of antiviral nucleosides.

PMID- 7625785
TI  - Combination effect of fosfomycin and ofloxacin against Pseudomonas aeruginosa
      growing in a biofilm.
AB  - We examined the combined effect of fosfomycin and ofloxacin against Pseudomonas
      aeruginosa in biofilms by using an in vitro experimental system with a modified
      Robbins device. Sessile cells in a mature or immature biofilm, developed on a
      silicon disk, were used, and an ATP bioluminescence assay was employed to assess
      antibacterial effects. A synergistic effect of fosfomycin and ofloxacin was
      clearly detected when concentrations at which each drug independently produced no
      detectable decrease in the bioactivity of sessile cells were used. Exposure of
      the cells in a mature biofilm to fosfomycin at concentrations of one-eighth of
      the MIC to 10 times the MIC (6.25 to 500 micrograms/ml) and ofloxacin at three or
      10 times the MIC (18.75 or 62.5 micrograms/ml) resulted in reduction of the
      bioactivity to 1.5 to 4.5% after 72 h. Young sessile cells in an immature biofilm
      were more susceptible to this combination therapy. With a combination of
      fosfomycin at three times the MIC and ofloxacin at three times the MIC, complete
      eradication was confirmed by both ATP assay and scanning electron microscopy.

PMID- 7625786
TI  - Interaction study of lomefloxacin and ciprofloxacin with omeprazole and
      comparative pharmacokinetics.
AB  - To assess whether or not concomitant omeprazole treatment influences the
      pharmacokinetics of lomefloxacin and ciprofloxacin, a randomized, double-blind
      four-way-crossover study was performed. Another objective was to compare the
      pharmacokinetics of lomefloxacin and ciprofloxacin. Twelve healthy volunteers
      participated. On days 1 to 4 of each study period, each of them took 20 mg of
      omeprazole or a placebo orally, and on day 4, each took 400 mg of lomefloxacin or
      500 mg of ciprofloxacin orally. Blood and urine samples were collected and
      assayed for the quinolones by high-pressure liquid chromatography. The mean peak
      concentrations in plasma (Cmax) and the areas under the curves (AUC),
      respectively, of lomefloxacin and ciprofloxacin, respectively, after prior
      treatment with placebo were 2.88 +/- 0.73 (mean +/- standard deviation) as
      against 2.60 +/- 0.76 micrograms/ml and 24.9 +/- 3.13 as against 11.9 +/- 1.89
      micrograms.h/ml, and 72.4% +/- 5.10% as against 36.1% +/- 7.50% of the doses of
      lomefloxacin and ciprofloxacin, respectively, were recovered from the urine. None
      of the pharmacokinetic parameters differed significantly after prior treatment
      with omeprazole compared with placebo. The Cmax of lomefloxacin was not
      significantly higher than that of ciprofloxacin, but lomefloxacin's AUC reached
      twice that of ciprofloxacin because of its significantly longer half-life in
      plasma (6.68 +/- 1.94 as against 4.15 +/- 0.92 h, respectively, P < or = 0.01).
      Concomitant therapy with omeprazole did not alter the pharmacokinetics of
      lomefloxacin or ciprofloxacin in these single-dose studies.

PMID- 7625787
TI  - Effect of fluconazole on pharmacokinetics of 2',3'-dideoxyinosine in persons
      seropositive for human immunodeficiency virus.
AB  - Fluconazole inhibits cytochrome P-450-mediated enzymatic metabolism of several
      drugs. Since hepatic metabolism is partially responsible for 2',3'-dideoxyinosine
      (didanosine or ddI) elimination, fluconazole therapy may lead to increased ddI
      concentrations in serum and subsequent concentration-dependent adverse effects.
      The purpose of this study was to determine if ddI pharmacokinetics are influenced
      by a 7-day course of oral fluconazole. Twelve adults with human immunodeficiency
      virus (HIV) who had received a constant dosage of ddI for at least 2 weeks were
      investigated. On study day 1, multiple serum samples for determination of ddI
      concentrations were obtained over 12 h. Then subjects received a 7-day course of
      oral fluconazole (200 mg every 12 h for two doses and then 200 mg once daily for
      6 days) while ddI therapy continued. Following the last dose of fluconazole,
      serum samples for determination of ddI concentrations were again obtained over 12
      h. ddI concentrations in serum were analyzed by radioimmunoassay. In contrast to
      previously published data, there was marked between-subject variability in ddI
      areas under the concentration-time curve, even when the dose was normalized for
      weight. No significant differences were found between mean ddI areas under the
      concentration-time curve from 0 to 12 h on study day 1 (1,528 +/- 902 ngx.hr/ml)
      and following fluconazole treatment (1,486 +/- 649 ngx.hr/ml) . There were no
      significant differences in other pharmacokinetic parameters, such as ddI peak
      concentrations in serum (971 +/- 509 and 942 +/- 442 ng/ml) or half-lives (80 +/-
      32 and 85 +/- 21 min.) before and after fluconazole treatment, respectively. We
      conclude that a 7-day course of oral fluconazole does not significantly alter ddI
      pharmacokinetics in adults that are infected with human immunodeficiency virus.

PMID- 7625788
TI  - Mathematical corrections for bacterial loss in pharmacodynamic in vitro dilution
      models.
AB  - In vitro dilution models are used to simulate in vivo drug concentration-time
      profiles and thus to study the effects of various antibiotic concentrations on
      the bacteria investigated. The major disadvantage of these models is permanent
      dilution of the bacterial culture, which falsifies the resulting kill curves.
      Known equations, which usually correct bacterial loss by simple first-order
      kinetics, do not take into account special test conditions, such as variable
      elimination rate constants, exceptionally long periods of investigation, or
      formation of biofilms. In the present investigation, we examined the validity of
      these equations with regard to the test conditions mentioned. We simulated the
      concentration-time curves resulting from continuous infusion of 1,000 mg of
      meropenem with steady-state levels of 2.5, 5.0, and 7.5 micrograms/ml in an in
      vitro dilution model. The resulting kill curves were compared with the kill
      curves obtained from incubation of bacteria in an undiluted system with meropenem
      at constant concentrations corresponding to the above-mentioned steady-state
      levels. Comparison of the matching kill curves showed that the common
      corrections, which do not consider the formation of biofilms in the compartments,
      partly overestimated the effect of bacterial dilution. We defined a factor, f, as
      an extension to the known equations which compensates for the effect of biofilms.
      Another extension was developed to allow the investigation of variable
      elimination rate constants. With the help of these extended mathematical
      corrections, we were able to fit the kill curves resulting from the in vitro
      dilution model exactly to the kill curves given by an undiluted system.

PMID- 7625789
TI  - Comparative single-dose pharmacokinetics of four quinolones, oxolinic acid,
      flumequine, sarafloxacin, and enrofloxacin, in Atlantic salmon (Salmo salar) held
      in seawater at 10 degrees C.
AB  - Quinolones are currently the most commonly used group of antimicrobial agents in
      Norwegian aquaculture. The aims of this study were to examine and compare the
      pharmacokinetic properties of the quinolones oxolinic acid, flumequine,
      sarafloxacin, and enrofloxacin after intravascular and oral administration to
      Atlantic salmon (Salmo salar) by using identical experimental designs. The study
      was performed in seawater at 10.2 +/- 0.2 degree C with Atlantic salmon weighing
      240 +/- 50 g (mean +/- standard deviation). The bioavailability varied
      considerably among the four quinolones. Following oral administration of
      medicated feed, the bioavailabilities of oxolinic acid, flumequine, sarafloxacin,
      and enrofloxacin were 30.1, 44.7, 2.2, and 55.5%, respectively. Taking the
      different dosages (25 mg/kg of body weight for oxolinic acid and flumequine and
      10 mg/kg for sarafloxacin and enrofloxacin) into account, enrofloxacin showed the
      highest maximum concentration in plasma, followed by flumequine, oxolinic acid,
      and sarafloxacin. Following intravenous administration, the volumes of
      distribution at steady state of oxolinic acid, flumequine, sarafloxacin, and
      enrofloxacin were 5.4, 3.5, 2.3, and 6.1 liters/kg, respectively. Hence, all the
      quinolones showed good tissue penetration in Atlantic salmon. The elimination
      half-life of three of the quinolones, oxolinic acid, flumequine, and
      sarafloxacin, was less than or equal to 24 h, with oxolinic acid showing the
      shortest (18.2 h). On the other hand, the elimination half-life of enrofloxacin
      was estimated to be 34.2 h, almost twice that of oxolinic acid. This study showed
      that flumequine and enrofloxacin had better pharmacokinetic properties, compared
      with those of oxolinic acid, in Atlantic salmon held in seawater.

PMID- 7625790
TI  - Therapeutic monitoring of experimental invasive pulmonary aspergillosis by
      ultrafast computerized tomography, a novel, noninvasive method for measuring
      responses to antifungal therapy.
AB  - Pulmonary infiltrates in neutropenic hosts with invasive aspergillosis are due to
      vascular invasion and hemorrhagic infarction. In order to measure the effect of
      antifungal compounds on this organism-mediated tissue injury, we monitored the
      course of pulmonary infiltrates by serial ultrafast computerized tomography
      (UFCT) in persistently granulocytopenic rabbits with experimental invasive
      pulmonary aspergillosis. The course of pulmonary lesions measured by serial UFCT
      scans was compared with those measured by conventional chest radiography,
      histopathological resolution of lesions, and microbiological clearance of
      Aspergillus fumigatus. Treatment groups included either amphotericin B colloidal
      dispersion in dosages of 1, 5, and 10 mg/kg of body weight per day intravenously
      or conventional desoxycholate amphotericin B at 1 mg/kg/day intravenously.
      Therapeutic monitoring of pulmonary lesions by UFCT demonstrated a significant
      dose-response relationship. Lesions continued to progress in untreated controls,
      whereas lesions in treated rabbits initially increased and then decreased in
      response to antifungal therapy in a dosage-dependent manner (P < or = 0.05 to P <
      or = 0.005, depending upon the groups compared). This same trend of resolution of
      lesions in response to antifungal therapy was also demonstrated by postmortem
      examination and by microbiological clearance of the organism. These data
      indicated that amphotericin B colloidal dispersion at 5 and 10 mg/kg/day exerted
      a more rapid rate of clearance of lesions than conventional amphotericin B. UFCT
      was more sensitive than conventional chest radiography in detecting lesions due
      to invasive pulmonary aspergillosis (P < 0.05 to P < 0.005, depending upon the
      groups compared). These findings establish a correlation among UFCT-defined
      lesions, microbiological response, and resolution of pathologically defined
      lesions in experimental invasive pulmonary aspergillosis. Serial monitoring of
      UFCT-defined lesions of aspergillosis provides a novel system for determining the
      antifungal response of organism-mediated tissue injury.

PMID- 7625791
TI  - In vitro evaluation of the pneumocandin antifungal agent L-733560, a new water
      soluble hybrid of L-705589 and L-731373.
AB  - Lipopeptide L-733560 is a hybrid analog of L-731373 and L-705589. All are water
      soluble semisynthetic pneumocandin Bo derivatives. In vitro susceptibility
      testing of L-705589, L-731373, and L-733560 against more than 200 clinical
      isolates consisting of eight Candida species, Cryptococcus neoformans, and three
      Aspergillus species was performed by the broth microdilution methods. All three
      pneumocandins exhibited potent anti-Candida activity and moderate anti-C.
      neoformans activity. However, anti-Aspergillus activity was demonstrated only by
      an agar disk diffusion method. Antifungal agent-resistant Candida species and C.
      neoformans showed susceptibility comparable to that of susceptible isolates.
      Growth inhibition kinetic studies against Candida albicans revealed fungicidal
      activity within 3 to 5 h. Drug combination studies with pneumocandins and
      amphotericin B revealed indifferent activity against C. albicans and additive
      effects against C. neoformans and Aspergillus fumigatus. The activities of the
      compounds were not dramatically affected by the presence of serum. Resistance
      induction studies showed that the susceptibility of C. albicans MY1055 was not
      significantly altered by repeated exposure to subinhibitory concentrations of L
      733560. Erythrocyte hemolysis studies indicated minimal hemolytic potential with
      pneumocandins. Results from preclinical evaluations and development studies
      performed thus far indicate that the pneumocandins should be safe, broad-spectrum
      fungicidal agents and potent parenteral antifungal agents.

PMID- 7625792
TI  - Evaluation of water-soluble pneumocandin analogs L-733560, L-705589, and L-731373
      with mouse models of disseminated aspergillosis, candidiasis, and cryptococcosis.
AB  - The activities of the water-soluble pneumocandin derivatives L-733560, L-705589,
      and L-731373 were evaluated in mouse models of disseminated aspergillosis,
      candidiasis, and cryptococcosis and were compared with those of commercially
      available antifungal agents. Pneumocandins are inhibitors of 1,3-beta-D-glucan
      synthesis. In the aspergillosis model, L-733560 and L-705589 significantly
      prolonged the survival of DBA/2N mice challenged intravenously with Aspergillus
      fumigatus conidia. L-733560 and L-705589 exhibited efficacies comparable to that
      of amphotericin B (AMB) with 90% effective doses of 0.48, 0.12, and 0.36 mg/kg of
      body weight, respectively. Two mouse models of disseminated candidiasis were used
      to evaluate these compounds. In both models, mice were challenged intravenously
      with Candida albicans. In a C. albicans survival model with DBA/2N and CD-1 mice,
      the efficacy of L-733560 was comparable to that of AMB, while L-731373 and L
      705589 were somewhat less active. In a previously described C. albicans target
      organ kidney assay, the pneumocandin analogs and AMB at doses of > or = 0.09
      mg/kg were effective in sterilizing kidneys, while fluconazole and ketoconazole
      were considerably less active and did not sterilize kidneys when they were used
      at concentrations of < or = 100 mg/kg. Although orally administered L-733560
      showed activity in both candidiasis models, its efficacy was reduced compared
      with that of parenterally administered drug. In a disseminated cryptococcosis
      mouse model that measures the number of CFU of Cryptococcus neoformans per gram
      of brain and spleen, L-733560 at 10 mg/kg was ineffective in reducing the counts
      in organs, while AMB at 0.31 mg/kg sterilized the organs. These results indicate
      that the pneumocandins may be beneficial as potent parenterally administered
      therapeutic agents for disseminated aspergillosis and candidiasis.

PMID- 7625793
TI  - Suction-induced blister fluid penetration of cefdinir in healthy volunteers
      following ascending oral doses.
AB  - The pharmacokinetics and suction-induced blister fluid penetration of cefdinir
      following single oral administrations of 200, 300, 400, and 600 mg were studied
      in 16 healthy young male volunteers according to a Latin square design. Plasma,
      blister, and urine samples were assayed by high-pressure liquid chromatography.
      We observed a nonlinear relationship (P = 0.02) between the dose and the maximum
      concentration in plasma as well as between the dose and the area under the
      concentration-time curve (AUC) in plasma (P < 0.001), which may be indicative of
      a limited absorption process. This resulted in a lower AUC value than expected as
      well as a smaller fraction of cefdinir excreted unchanged at a dose of 600 mg.
      Renal clearance decreased with increasing doses (P < 0.006; analysis of variance
      with the Latin square design and Games-Howell procedure). Maximal cefdinir
      concentrations in blister fluid were delayed compared with concentrations in
      plasma. Blister fluid penetration measured by the ratio of the AUC in blister
      fluid to the AUC in plasma was extensive (92.4 to 108.4%). Cefdinir
      concentrations in blister fluid remained equal to or higher than the
      concentrations in plasma from 6 to 12 h following cefdinir administration. On the
      basis of the concentrations in blister fluid and the in vitro MIC data, we
      estimated that cefdinir at 200 to 400 mg administered twice daily would be
      adequate to treat uncomplicated skin infections caused by Streptococcus pyogenes.
      Seven volunteers experienced episodes of light-to-moderate diarrhea. These
      adverse events occurred irrespective of dose.

PMID- 7625794
TI  - Effects of MICs and sub-MICs of antibiotics on production of capsular
      polysaccharide of Klebsiella pneumoniae.
AB  - In the present study, we examined whether MICs and sub-MICs of antimicrobial
      agents belonging to two different classes, ciprofloxacin and ceftazidime, were
      able to influence the production and release of cell-associated and soluble
      (extracellular) capsular polysaccharide (CPS), respectively, in a heavily
      encapsulated strain of Klebsiella pneumoniae (B5055). Using a CPS-specific enzyme
      linked immunosorbent assay, we found that the amount of cell-associated CPS
      increased in a dose-dependent manner by more than 10-fold under the influence of
      the MIC of ceftazidime and by more than 100-fold under the influence of the MIC
      of ciprofloxacin. The largest amounts of CPS were measured by using the MIC of
      either antibiotic substance. Electron microscopic studies showed that the
      diameter of the capsule was significantly increased compared with the diameter
      for untreated controls. Thus, both antimicrobial agents genuinely stimulated CPS
      production.

PMID- 7625795
TI  - Comparative in vitro activities of azithromycin, Bay y 3118, levofloxacin,
      sparfloxacin, and 11 other oral antimicrobial agents against 194 aerobic and
      anaerobic bite wound isolates.
AB  - The activities of sparfloxacin, levofloxacin, Bay y 3118, azithromycin,
      cefprozil, loracarbef, and nine other oral antimicrobial agents against 194
      aerobic and anaerobic clinical bite wound isolates were determined by the agar
      dilution method. Sparfloxacin, levofloxacin, and Bay y 3118 were active against
      all aerobic isolates (MICs at which 90% of the isolates are inhibited [MIC90], <
      or = 1.0 microgram/ml for sparfloxacin and levofloxacin and 0.1 microgram/ml for
      Bay y 3118) and many anaerobic isolates, with the exception of the fusobacteria.
      Azithromycin was more active than erythromycin by 1 to 2 dilutions against many
      aerobes, including Pasteurella multocida and Eikenella corrodens, and by 2 to 4
      dilutions against anaerobic isolates. Cefprozil was more active (MIC90, < or = 1
      microgram/ml) than loracarbef (MIC90, < or = 4 micrograms/ml) against aerobic
      gram-positive isolates, but both had poor activity (MIC90, > or = 16
      micrograms/ml) against peptostreptococci. Both cefprozil and loracarbef had
      MIC90s of < or = 0.5 micrograms/ml against P. multocida.

PMID- 7625796
TI  - Pharmacokinetics of dapsone in human immunodeficiency virus-infected children.
AB  - Dapsone, administered at various doses and schedules, has been proven to be a
      safe and effective alternative to trimethoprim-sulfamethoxazole for prevention of
      Pneumocystis carinii pneumonia (PCP) in adults with human immunodeficiency virus
      (HIV) infection. Dapsone is also recommended by the Centers for Disease Control
      for PCP prophylaxis in HIV-infected children. However, the suggested dosage
      regimen is based upon clinical experience with children with leprosy and
      dermatitis herpetiformis rather than pharmacokinetic and pharmacodynamic data
      obtained from the target patient population. In order to determine a rational
      dosage regimen that could be tested in clinical studies aimed at the evaluation
      of dapsone for the prevention of PCP in HIV-infected children, we studied the
      pharmacokinetics of dapsone following a 2-mg/kg of body weight oral dose in
      twelve HIV-positive children aged 9 months to 9 years. Plasma was collected at
      the following times after dapsone administration: 0, 2, 4, 6, 12, 24, 48, 72, and
      96 h. The levels of dapsone in plasma were determined by high-performance liquid
      chromatography. Data were analyzed by noncompartmental methods. Expressed as
      means +/- standard deviations (ranges), the pharmacokinetic parameters were as
      follows: peak concentration in plasma, 1.12 +/- 0.48 (0.44 to 1.81) mg/liter;
      time to peak concentration in plasma, 3.8 +/- 1.3 (2 to 6) h; half-life at
      elimination phase, 24.2 +/- 7.1 (14.4 to 35.0) h; clearance from plasma divided
      by bioavailability (CL/F), 1.15 +/- 0.67 (0.37 to 2.63) ml/min/kg; and volume of
      distribution divided by bioavailability (V/F), 2.25 +/- 1.20 (1.00 to 4.57)
      liters/kg. Oral CL correlated negatively with age (r = 0.614 and P = 0.034), as
      did V (r = 0.631 and P = 0.028). As a consequence of the high interindividual
      variability in growth retardation, pharmacokinetic parameters correlated with
      measures of body development better than they did with age (e.g., for CL/F to
      height, r = 0.765 and P = 0.004, and for V/F to height, r = 0.748 and P = 0.005).
      Since oral CL from plasma and V were positively and highly correlated (r = 0.898
      and P = 0.0001), a lower absolute F may be the cause, in part, of higher values
      for CL/F and V/F in smaller children. The results of this study warrant the
      testing of a 2-mg/kg dose of dapsone administered twice or thrice weekly to HIV
      infected children. The monitoring of drug levels in plasma and dosage adjustment
      may be necessary for smaller children.

PMID- 7625798
TI  - Comparison of efficacies of famciclovir and valaciclovir against herpes simplex
      virus type 1 in a murine immunosuppression model.
AB  - A mouse model of herpes simplex virus type 1 infection in an immunocompromised
      host was established by using cyclosporin-A to impair T-cell function. Following
      inoculation of herpes simplex virus type 1 into the skin of the ear pinna,
      cyclosporin-A prolonged virus replication in the skin and neural tissues compared
      with that in immunocompetent mice. This model was used to investigate the
      activity of famciclovir (FCV) and valaciclovir (VACV), which are oral products of
      the antiherpesvirus agents penciclovir and acyclovir, respectively. Both prodrugs
      gave similar blood profiles of the antiherpesvirus agents in normal and
      cyclosporin-treated mice. The compounds were administered by the oral route at 50
      mg/kg per dose twice daily for 5 days. Both compounds were very effective at
      clearing infectious virus from the tissues despite the immunosuppression; FCV
      treated animals cleared virus from the ear pinna more rapidly than VACV-treated
      animals. The areas under the concentration-time curve (AUC) for virus replication
      with time were reduced to 50 and 30% of control values for ear pinna and brain
      stem, respectively, with VACV therapy and to < 5% in both tissues by FCV. When
      treatment was continued to day 10, the reductions in AUC for ear and brain stem,
      respectively, were to 33 and 26% of control values with VACV and to < 3 and < 5%
      with FCV. However, on cessation of the antiviral treatment, there was a
      reproducible recurrence of infectious virus in the tissues obtained from VACV
      treated mice. The recurrence of infectious virus was also evident after 10 days
      of treatment with VACV. In mice which had received FCV for 10 or 5 days, these
      was no resumption of virus replication in the ear pinna or brain stem. When
      dosing was reduced to once per day, both compounds were less effective at
      controlling the infection. Nevertheless, no recurrence of infectious virus was
      observed on cessation of FCV therapy.

PMID- 7625797
TI  - Frequency of diminazene-resistant trypanosomes in populations of Trypanosoma
      congolense arising in infected animals following treatment with diminazene
      aceturate.
AB  - The frequency of trypanosomes resistant to diminazene aceturate at a dose of 25
      mg/kg of body weight was investigated for populations of Trypanosoma congolense
      IL 3274 which reappeared in infected mice after intraperitoneal treatment with
      diminazene aceturate at the same dosage. At inoculum sizes of 10(2), 10(3),
      10(4), 10(5), and 10(6) trypanosomes per mouse, the relapse populations were used
      to initiate infections in five groups of 100 mice each by the intravenous route.
      Immediately after infection, 50 mice in each group were treated intraperitoneally
      with diminazene aceturate at the aforementioned dosage; the other 50 mice
      functioned as untreated controls. Thereafter, all animals were monitored for 100
      days for the presence of trypanosomes. In each group, trypanosomes were detected
      in 50 of 50 control mice, indicating 100% infectivity for all five inoculum
      sizes. In contrast, in the groups of 50 mice infected with 10(2), 10(3), 10(4),
      10(5) and 10(6) trypanosomes and treated with diminazene aceturate, trypanosomes
      were detected in 4, 11, 13, 28, and 39 of 50 mice, respectively. By logistic
      regression, a good fit was found between the number of mice identified as
      parasitemic and the inoculum sizes. Maximum likelihood estimates for the
      proportions of trypanosomes resistant to diminazene aceturate at 25 mg/kg of body
      weight for the inoculum of 10(2), 10(3), 10(4), 10(5), and 10(6) organisms were
      8.335 x 10(-4), 2.485 x 10(-4), 3.02 x 10(-5), 8.3 x 10(-6), and 1.6 x 10(-6),
      respectively. These finding indicate that the majority of the relapse
      trypanosomes were susceptible the the drug dosage used for selecting the
      population and that, surprisingly, the calculated proportion of organisms which
      survived drug exposure varied inversely with the inoculum size. Further
      experiments with mice indicated that the inverse relationship did not result from
      alterations in the pharmacokinetics of the drug with different inoculum sizes.
      The data therefore suggest that parasite inoculum size and drug dosage are
      important factors in estimating the apparent frequency of diminazene-resistant
      trypanosomes in populations of T. congolense occurring in vivo.

PMID- 7625799
TI  - TOC-39, a novel parenteral broad-spectrum cephalosporin with excellent activity
      against methicillin-resistant Staphylococcus aureus.
AB  - TOC-39, a new parenteral cephalosporin, is a hydroxyimino-type cephem antibiotic
      with vinylthio-pyridyl moiety at the 3 position. TOC-39 was evaluated for
      antibacterial activity against various clinically isolated strains. TOC-39 had
      excellent activity, stronger than that of methicillin, oxacillin, the
      cephalosporins tested, imipenem, gentamicin, minocycline, tobramycin, ofloxacin,
      and ciprofloxacin against methicillin-resistant Staphylococcus aureus (MRSA) and
      had an MIC comparable to that of vancomycin (the MICs of TOC-39 and vancomycin
      for 90% of the strains tested were 3.13 and 1.56 micrograms/ml, respectively).
      Against Enterococcus faecalis strains, which are resistant to cephalosporins, TOC
      39 was twice as active as ampicillin. Against methicillin-susceptible S. aureus,
      coagulase-negative Staphylococcus spp., and Streptococcus pneumoniae, TOC-39 was
      twice as active as or more active than cefotiam, ceftazidime, flomoxef, and
      cefpirome. Against Streptococcus pyogenes, TOC-39 was superior to cefotiam,
      ceftazidime, and flomoxef and was similar to cefpirome. In addition, the activity
      of TOC-39 was equal to or greater than that of cefotiam, ceftazidime, flomoxef,
      and cefpirome against Haemophilus influenzae, Escherichia coli, Klebsiella
      pneumoniae, Proteus mirabilis, and Morganella morganii. In terms of bactericidal
      effect against MRSA, TOC-39 was superior to vancomycin. No mutant resistant to
      TOC-39 or vancomycin was obtained from susceptible MRSA strains. In murine
      systemic infection models, TOC-39 showed potent activity against S. aureus and E.
      coli. Against highly MRSA, the activity of TOC-39 was comparable to that of
      vancomycin.

PMID- 7625800
TI  - Effects of penicillin, ceftriaxone, and doxycycline on morphology of Borrelia
      burgdorferi.
AB  - Antibiotic therapy with penicillin, doxycycline, and ceftriaxone has proven to be
      effective for the treatment of Lyme borreliosis. In some patients, however, it
      was noticed that borreliae can survival in the tissues in spite of seemingly
      adequate therapy. For a better understanding of this phenomenon, we investigated
      the different modes of degeneration of Borrelia burgdorferi suspensions during a
      96-h exposure to various antibiotics. By dark-field microscopy and
      ultrastructural investigations, increasing blebbing and the gradual formation of
      granular and cystic structures could be followed during the exposure time.
      Although antibiotic concentrations at the MIC at which 90% of organisms are
      inhibited after 72 h were 80% or even greater, motile organisms were still
      present after incubation with penicillin and doxycycline but not after incubation
      with ceftriaxone. By transmission electron microscopy, intact spirochetal parts,
      mostly situated in cysts, were seen up to 96 h after exposure with all three
      antibiotics tested. According to experiences from studies with other spirochetes
      it is suggested that encysted borreliae, granules, and the remaining blebs might
      be responsible for the ongoing antigenic stimulus leading to complaints of
      chronic Lyme borreliosis.

PMID- 7625801
TI  - In vivo verification of in vitro model of antibiotic treatment of device-related
      infection.
AB  - Device-related infections are difficult to treat with antibiotics alone. Standard
      susceptibility tests do not correlate with treatment success. Therefore, the
      utility of a pharmacokinetic in vitro model has been evaluated in comparison with
      the tissue-cage infection model in guinea pigs. The bactericidal activity of 28
      treatment regimens has been studied by using three different test strains. In
      vitro efficacy was defined as reduction in the number of suspended or adherent
      bacteria, and in vivo efficacy was defined as reduction in the number of bacteria
      in tissue-cage fluid. Test results between the two models (in vivo and in vitro)
      correlated well, with correlation coefficients of 0.85 for in vivo efficacy
      versus in vitro efficacy against suspended bacteria and 0.72 for in vivo efficacy
      versus in vitro efficacy against adherent bacteria (P < 0.05) for Staphylococcus
      aureus, 0.96 and 0.82 (P < 0.05) for Staphylococcus epidermidis, and 0.89 and
      0.97 for Escherichia coli, respectively. In contrast, standard susceptibility
      tests, ratios of MICs to trough or peak levels, ratios of the area under the
      curve to the MIC, or time above the MIC were not predictive for therapeutic
      outcome in either the in vitro or in vivo model. In both models, the bactericidal
      activity levels with combination regimens were significantly higher than those
      with single-drug regimens (P < 0.001). Furthermore, rifampin combinations with
      either vancomycin, teicoplanin, fleroxacin, or ciprofloxacin were significantly
      more bactericidal against adherent bacteria than netilmicin combinations with
      vancomycin or daptomycin (P < 0.01). Thus, in vivo verification of the
      pharmacokinetic in vitro model correlated well with the animal model. The in
      vitro model offers an alternative to ther animal model in experiments that screen
      and assess antibiotic regimens against device-related infections.

PMID- 7625802
TI  - Randomized comparison of meropenem with cefotaxime for treatment of bacterial
      meningitis. Meropenem Meningitis Study Group.
AB  - Broad-spectrum cephalosporins are drugs of choice for the treatment of meningitis
      in communities which can afford them. The emergence of cephalosporin-resistant
      pneumococci demands the clinical trial of alternate agents. Carbapenems are
      active against the bacteria causing meningitis, but the use of imipenem
      cilastatin was frustrated by drug-associated seizures. The safety and efficacy of
      meropenem, a new carbapenem, were compared to those of cefotaxime in a
      prospective randomized trial of 190 children with bacterial meningitis. Seizures
      occurred within 24 h before antibiotic therapy in 16 of 98 patients (16%)
      randomized to receive meropenem and in 6 of 92 patients (7%) randomized to
      receive cefotaxime. In patients without seizures before therapy, seizures
      occurred during therapy in 5 of 82 patients (6%) receiving meropenem and in 1 of
      86 patients (1%) receiving cefotaxime (95% confidence interval: -0.7%, 10.6%).
      None were thought to be drug related. Twenty-four meropenem-treated patients
      (24%) and 11 cefotaxime-treated patients (12%) had neurological abnormalities
      before therapy. In patients without pretherapy neurological abnormalities, these
      abnormalities were present after treatment in 4 of 74 meropenem-treated patients
      (5%) and in 2 of 81 cefotaxime-treated patients (2%) (95% confidence interval: 
      3.2%, 9.1%). Of 75 meropenem-treated and 64 cefotaxime-treated patients with
      pretherapy positive cerebrospinal-fluid cultures, 68 and 59, respectively, had
      repeat lumbar punctures. Bacterial eradication was found to be 100% in both
      groups. Our data suggest that meropenem may be a carbapenem agent that is well
      tolerated and effective in the treatment of bacterial meningitis.

PMID- 7625803
TI  - Tn5384, a composite enterococcal mobile element conferring resistance to
      erythromycin and gentamicin whose ends are directly repeated copies of IS256.
AB  - We have identified a 26-kb mobile element from Enterococcus faecalis CH116,
      designated Tn5384, which confers resistance to erythromycin and to high levels of
      gentamicin. Tn5384 is a composite element containing three copies of insertion
      element IS256. Two of the IS256 copies flank the aac6'-aph2" bifunctional
      aminoglycoside-modifying-enzyme gene in the inverted orientation, forming a
      structure similar to staphylococcal gentamicin resistance transposon Tn4001. One
      of the IS256 elements involved in the Tn4001-like structure also forms the left
      end of Tn5384, the right end of which is a directly repeated insertion of IS256
      approximately 23 kb downstream of the leftmost insertion. Insertions of Tn5384
      into enterococcal plasmid pLRM1 have been found associated with 8- and 9-bp
      duplications of the target sequence.

PMID- 7625804
TI  - Fluconazole penetration in cerebral parenchyma in humans at steady state.
AB  - We studied fluconazole penetration in the brain in five patients who had a deep
      cerebral tumor whose removal required the excision of healthy brain tissue.
      Plasma and brain samples were simultaneously obtained after oral ingestion of 400
      mg of fluconazole daily for 4 days (90% of steady state). Fluconazole penetration
      in healthy cerebral parenchyma was determined. Plasma and brain samples were
      assayed by high-pressure liquid chromatography. Concentrations in plasma and
      brain tissue were 13.5 +/- 5.5 micrograms/ml and 17.6 +/- 6.6 micrograms/g,
      respectively. The average ratio of concentrations in the brain and plasma (four
      patients) was 1.33 (range, 0.70 to 2.39). Despite the lack of data concerning the
      penetration of fluconazole in brain abscesses, these results should permit the
      use of a daily dose of 400 mg of fluconazole in prospective clinical studies that
      evaluate the effectiveness of this drug in the treatment of brain abscesses due
      to susceptible species of fungi.

PMID- 7625805
TI  - Potent antiviral activity of an antisense oligonucleotide complementary to the
      intron-exon boundary of human cytomegalovirus genes UL36 and UL37.
AB  - An antisense phosphorothioate oligonucleotide complementary to the intron-exon
      boundary of human cytomegalovirus genes UL36 and UL37 (UL36ANTI) reduced the
      yield of infectious virus by 99% and inhibited human cytomegalovirus DNA
      replication at a concentration of 0.08 microM. In addition, oligonucleotides with
      base substitutions which resulted in base pair mismatches showed lesser degrees
      of activity, indicating a sequence-specific antisense mechanism. UL36ANTI was
      also shown to inhibit DNA replication of ganciclovir-resistant strains and human
      cytomegalovirus clinical isolates.

PMID- 7625806
TI  - In vitro activity of roxithromycin against the Mycobacterium tuberculosis
      complex.
AB  - Roxithromycin has recently been shown to possess significant in vitro activity
      against a variety of atypical mycobacteria such as the M. avium complex, M.
      scrofulaceum, M. szulgai, M. malmoense, M. xenopi, M. marinum, and M. kansasii
      and rare pathogens like M. chelonei and M. fortuitum. In the present
      investigation, screening of its in vitro activity was further extended by testing
      it against 34 strains belonging to the M. tuberculosis complex (including M.
      tuberculosis, M. africanum, M. bovis, and M. bovis BCG). The MICs were determined
      by the radiometric BACTEC 460-TB methodology at pHs of both 6.8 and 7.4, as well
      as with 7H10 agar medium by the 1% proportion method. With the exception of M.
      bovis BCG (MIC ranges, 0.5 to 4 micrograms/ml at pH 6.8 and 0.25 to 2
      micrograms/ml at pH 7.4), MICs for all of the isolates were significantly greater
      (MIC ranges, 32 to > 64 micrograms/ml at pH 6.8 and 16 to > 32 micrograms/ml at
      pH 7.4) than those reported previously for atypical mycobacteria. Roxithromycin
      MICs of 64 or > 64 micrograms/ml for all of the M. tuberculosis isolates screened
      were found by the 7H10 agar medium method. Roxithromycin, however, showed a pH
      dependent bactericidal effect against M. tuberculosis because the drug was
      relatively more active when it was used at pH 7.4 than when it was used at pH
      6.8. We conclude that roxithromycin per se is not a drug of choice for the
      treatment of M. tuberculosis infection or disease; however, considering its
      pharmacokinetics, eventual anti-tubercle bacillus activity in an in vivo system
      cannot yet be excluded. We suggest that the use of roxithromycin in
      chemoprophylactic regimens for the prevention of opportunistic infections
      (including M. avium complex infections) in patients with AIDS should be carefully
      monitored, and patients should be enrolled in such a regimen only after it has
      been excluded that the patient das an underlying infection of disease caused by
      M. tuberculosis.

PMID- 7625807
TI  - Antimicrobial activities of beta-lactam antibiotics and gentamicin against
      penicillin-susceptible and penicillin-resistant pneumococci.
AB  - The MICs of penicillin and cefotaxime for a range of penicillin-susceptible and
      penicillin-resistant isolates of Streptococcus pneumoniae were unchanged by the
      addition of gentamicin. In time-kill studies the rate of killing was greater for
      18 of 20 isolates in the presence of gentamicin. However, mean differences in
      killing after 6 h of incubation were modest, not exceeding 1 log10 unit.

PMID- 7625808
TI  - Activities of the triazole SCH 51048 against Coccidioides immitis in vitro and in
      vivo.
AB  - The activity of the novel triazole SCH 51048 was tested against Coccidioides
      immitis. SCH 51048 inhibited C. immitis in vitro; MICs for 13 isolates ranged
      from < or = 0.39 to 0.78 micrograms/ml, and minimum fungicidal concentrations
      ranged from < or = 0.39 to 1.6 micrograms/ml. In vivo, no mice treated with SCH
      51048 at 2 to 50 mg/kg of body weight or 100 mg of fluconazole or itraconazole
      per kg died of systemic coccidioidomycosis, whereas 60 to 100% of the control
      mice died. SCH 51048 given at 25 or 50 mg/kg was curative, whereas fluconazole or
      itraconazole given at 100 mg/kg was not curative. Pharmacokinetic studies showed
      peak levels in serum of > 14 micrograms/ml, with an estimated half-life of > 12
      h. SCH 51048 was 5- to 50-fold or more superior to fluconazole or itraconazole.

PMID- 7625809
TI  - Concentration-dependent synergy and antagonism between cefoperazone and imipenem
      against methicillin-resistant Staphylococcus aureus.
AB  - By the agar dilution checkerboard method, striking synergy between cefoperazone
      and imipenem was observed with 32 strains of methicillin-resistant Staphylococcus
      aureus (fractional inhibitory concentration indices, < or = 0.03 to 0.34; mean,
      0.12 +/- 0.08). By the double-disk diffusion method, the synergy was confirmed,
      but about 60% of strains showed antagonism manifest by truncation of the zone of
      inhibition around cefoperazone. The mechanism may involve auxiliary factors
      distinct from those essential for the expression of methicillin resistance.

PMID- 7625810
TI  - Comparative antibacterial activity of L-695,256, a carbapenem active against
      methicillin-resistant staphylococci.
AB  - The activity of a new prototype carbapenem, L-695,256, against clinical isolates
      of gram-positive and gram-negative aerobes was studied in vitro by agar dilution.
      L-695,256 was highly active against methicillin-resistant and -susceptible
      isolates of staphylococci (MICs, 0.016 to 2 micrograms/ml) and against penicillin
      resistant pneumococci (MICs, 0.016 to 0.064 micrograms/ml), irrespective of
      penicillin susceptibility. Activity against members of the family
      Enterobacteriaceae was less than that of imipenem, while Proteus mirabilis and
      Morganella morganii were more susceptible to L-695,256.

PMID- 7625811
TI  - Concentration of pefloxacin in feces during infection prophylaxis in neutropenic
      patients.
AB  - Pefloxacin (400 mg twice daily) was administered orally for infection prophylaxis
      in neutropenic patients. Diffusible fecal pefloxacin concentration was determined
      by bioassay during 24 neutropenic periods. The median diffusible fecal pefloxacin
      concentration was 187 micrograms/g. This concentration was comparable with those
      found in volunteers following oral and intravenous administration of pefloxacin
      (400 mg twice daily) (median of 171 and 155 micrograms/g, respectively). From
      this study, it is concluded that pefloxacin administered orally results in a
      predictable high diffusible fecal concentration which leads to effective
      elimination of susceptible aerobic gram-negative bacilli from the colonic flora.

PMID- 7625814
TI  - Safety and pharmacokinetics of vitamin A therapy for infants with respiratory
      syncytial virus infections.
AB  - Infants with respiratory syncytial virus infection have low serum vitamin A
      levels. We treated 21 respiratory syncytial virus-infected children with 12,500
      to 25,000 IU of oral vitamin A. Vitamin A levels were normalized at 6 h, and none
      of the children experienced vitamin A toxicity or exacerbation of respiratory
      illness. Vitamin A treatment of previously healthy respiratory syncytial virus
      infected infants at these doses is safe and well tolerated.

PMID- 7625812
TI  - In vitro activity of rokitamycin, a new macrolide, against Borrelia burgdorferi.
AB  - The activity of rokitamycin, a new macrolide with a 16-member ring, was tested
      against Borrelia burgdorferi in vitro. The antibiotic had a lower MIC at which
      50% of the isolates are inhibited than erythromycin, the parent 14-member
      macrolide, but the same MIC at which 50% of the isolates are inhibited as the
      other recent 14- and 15-member macrolides, like clarithromycin and azithromycin.
      The MBC was equal to the MIC at which 50% of the isolates are inhibited, so
      rokitamycin can be considered bactericidal against B. burgdorferi. The
      sensitivity of the Borrelia strains tested was not correlated with the particular
      species Burgdorferi sensu stricto, B. garinii, and B. afzelii or with the number
      of subcultures of the isolates.

PMID- 7625813
TI  - In vitro activities of various beta-lactam antimicrobial agents against clinical
      isolates of Escherichia coli and Klebsiella spp. resistant to oxyimino
      cephalosporins.
AB  - Broth microdilution testing was used to study the activity of several beta-lactam
      antimicrobial agents, including piperacillin-tazobactam and cefepime, against 108
      clinically derived Escherichia coli and Klebsiella sp. strains resistant to
      oxyimino cephalosporins (i.e., putative extended-spectrum beta-lactamase
      producers). On the basis of the percentage of susceptible strains, imipenem
      (100%), cefotetan (> or = 92%), and piperacillin-tazobactam (> or = 86%) were the
      most active agents. Cefepime activity (52 to 64% susceptible) was comparable to
      that of cefotaxime (40 to 63% susceptible) and aztreonam (20 to 63% susceptible).
      Among all beta-lactams tested, imipenem and cefotetan demonstrated the highest
      and most consistent level of activity and were the least affected by challenges
      with increased sizes of inocula of these resistant organisms.

PMID- 7625815
TI  - Susceptibilities of Brucella melitensis isolates to clinafloxacin and four other
      new fluoroquinolones.
AB  - The susceptibilities of 120 clinical isolates of Brucella melitensis and 3
      reference strains of the same species to six fluoroquinolones (clinafloxacin, PD
      117596, PD 131628, PD 138312, PD 140248, and ciprofloxacin) were examined by agar
      dilution MIC methodology. Clinafloxacin was the most active compound tested (MIC
      at which 50% of strains tested were inhibited [MIC50] and MIC90 of 0.06
      micrograms/ml). Its level of activity was slightly higher than that of PD 117596
      (MIC50 and MIC90 of 0.12 micrograms/ml). PD 131628 and ciprofloxacin were less
      active than clinafloxacin, with MIC50s ranging from 0.12 to 0.25 micrograms/ml
      and MIC90s of between 0.25 and 0.5 micrograms/ml for the two compounds. The
      activity levels of PD 138312 and PD 140248, with MIC50s ranging from 1 to 2
      micrograms/ml and MIC90s of 4 to 8 micrograms/ml, were lower than those of the
      other fluoroquinolones tested.

PMID- 7625816
TI  - Trends in antimicrobial resistance of Streptococcus pneumoniae in Japan.
AB  - A total of 184 isolates of Streptococcus pneumoniae were recovered from the sputa
      of patients over a 5-year period in the Nagasaki area and were examined. A total
      of 30 strains were resistant to penicillin (MIC, > or = 0.10 micrograms/ml), 13
      of which belonged to serotype 19B. These strains showed decreased susceptibility
      to other antimicrobial agents. Vancomycin, cefpirome, and imipenem were the most
      active agents tested.

PMID- 7625817
TI  - New variant of TEM-10 beta-lactamase gene produced by a clinical isolate of
      proteus mirabilis.
AB  - A clinical isolate of Proteus mirabilis was found to produce a new variant of the
      TEM-10 beta-lactamase gene. This is the first report of TEM-10 production by P.
      mirabilis and the first report of extended-spectrum beta-lactamase production by
      an isolate of this species recovered in the United States.

PMID- 7625819
TI  - Novel mutation in the UL97 gene of a clinical cytomegalovirus strain conferring
      resistance to ganciclovir.
AB  - Characterization of a ganciclovir-resistant cytomegalovirus strain from a patient
      with AIDS showed a histidine-to-glutamine change at residue 520 of UL97 (Q520
      mutation). In anabolism studies, Q520 was associated with impaired
      phosphorylation of ganciclovir. Transfer of Q520 to a recombinant virus resulted
      in a ganciclovir-resistant phenotype.

PMID- 7625818
TI  - Mutation in the gyrA gene of quinolone-resistant clinical isolates of
      Acinetobacter baumannii.
AB  - The gyrA gene mutations associated with quinolone resistance were determined in
      21 epidemiologically unrelated clinical isolates of Acinetobacter baumannii. Our
      studies highlight the conserved sequences in the quinolone resistance-determining
      region of the gyrA gene from A. baumannii and other bacteria. All 15 isolates for
      which the MIC of ciprofloxacin is > or = 4 micrograms/ml showed a change at Ser
      83 to Leu. Six strains for which the MIC of ciprofloxacin is 1 microgram/ml did
      not show any change at Ser-83, although a strain for which the MIC of
      ciprofloxacin is 1 microgram/ml exhibited a change at Gly-81 to Val. Although it
      is possible that mutations in other locations of the gyrA gene, the gyrB gene, or
      in other genes may also contribute to the modulation of the MIC level, our
      results suggest that a gyrA mutation at Ser-83 is associated with quinolone
      resistance in A. baumannii.

PMID- 7625820
TI  - Results of German multicenter study of antimicrobial susceptibilities of
      Trichophyton rubrum and Trichophyton mentagrophytes strains causing tinea
      unguium. German Collaborative Dermatophyte Drug Susceptibility Study Group.
AB  - Thirty-two strains of Trichophyton rubrum and 16 strains of Trichophyton
      mentagrophytes isolated from patients with tinea unguium in various parts of
      Germany were subjected to a microdilution test with six systemic or topical
      antimycotic agents. Apart from griseofulvin, there were no species-specific
      differences between the two species. Terbinafine was the most active antimycotic
      agent, with a MIC not exceeding 0.05 micrograms/ml.

PMID- 7625821
TI  - Oxacillin hydrolysis by the LCR-1 beta-lactamase.

PMID- 7625823
TI  - Improvement of Escherichia coli cell-free system by utilization of cell extract
      having additional property. Problems and countermeasures.
AB  - In the Escherichia coli cell-free system, the modification of cell extract can be
      achieved by preparation of the strains carrying additional property or those
      being induced with a certain gene expression prior to harvesting. In this study,
      we analyzed the cell-free system with S30 extract containing T7 RNA polymerases
      (S30 extract-T7pol) prepared from E. coli BL21(DE3) strain, which includes T7 RNA
      polymerase from extrinsic genes by IPTG induction, as a model for the improvement
      of the cell-free system. The fact that a significant degree of mRNA degradation
      was observed in the cell-free system with S30 extract-T7pol indicates the
      increase of ribonuclease activity was an unfavorable influence derived from the
      cell-extract modification process. We also showed that this influence was settled
      by the addition of an effective ribonuclease inhibitor, such as copper (II) ion,
      to the reaction mixture.

PMID- 7625822
TI  - Preparation of deglycosylated egg white avidin.
AB  - A simple procedure for the preparation of deglycosylated avidin is described.
      Commercially obtained avidin was treated with a mixed microbial culture. The
      cells were capable of growing on the oligosaccharide residues, but generally
      ignored the polypeptide portion of the egg white glycoprotein. The resultant
      deglycosylated avidin retained its biotin-binding characteristics. The major
      bacterial strain (strain BECH080), responsible for the deglycosylation, was
      isolated. On the basis of elementary biochemical tests, fatty acid, and
      phenotypic analyses, the isolate was identified as a strain of Flavobacterium
      meningosepticum. The primary enzymatic activity that caused the removal of the
      oligosaccharide residues of avidin appeared to be similar to endoglycosidase F.

PMID- 7625824
TI  - High-resolution proton nuclear magnetic resonance studies of urine from
      asphyxiated newborn infants.
AB  - High-resolution proton nuclear magnetic resonance spectroscopy was used to study
      human urine obtained from 10 normal babies and twenty babies with various degrees
      of neonatal asphyxia, respiratory distress syndrome (RDS), and meconium
      aspiration syndrome (MAS). All sick babies showed different degrees of oxygen
      deficiency, indicated by an obvious increase of the lactate signal level in the
      urine spectra. Changes in the concentration of other urinary metabolites produced
      from the citric acid cycle were also observed. In extremely serious cases, the
      signals of some of the major components, including citrate, alpha-ketoglutarate,
      and succinate, simply disappeared. The spectra of urine, serum, and CSF of an
      infant suffering from SIDS showed common characteristics of the metabolites.

PMID- 7625826
TI  - Microsomal glutathione transferase: lipid-derived substrates and lipid
      dependence.
AB  - Rat liver microsomal glutathione transferase was found to display glutathione
      peroxidase activity toward a variety of oxidized lipids. 1-Linoleoyl-2-palmitoyl
      phosphatidylcholine hydroperoxide, 2-linoleoyl-1-palmitoyl phosphatidylcholine
      hydroperoxide, 2-linoleoyl-1-palmitoyl phosphatidylethanolamine hydroperoxide,
      and cholesteryl linoleate hydroperoxide all served as substrates (0.02, 0.04,
      0.02, and 0.02 mumol/min mg, respectively). The phospholipid hydroperoxide
      glutathione peroxidase activity of the enzyme was found not to require detergent
      and increased when liposomes containing peroxidized phospholipid were fused with
      liposomes containing microsomal glutathione transferase. Methyl linoleate ozonide
      serves as a very efficient substrate for the microsomal glutathione transferase.
      The unactivated and N-ethylmaleimide-activated enzyme displayed specific
      activities of 0.74 and 5.9 mumol/min mg, respectively. Upon examination of a
      series of 4-hydroxyalk-2-enals it was found that the catalytic efficiency of the
      enzyme increases from the 4-hydroxyhept-2-enal up to the 4-hydroxytetradec-2
      enal. The specific activities with the various 4-hydroxyalk-2-enals tested varied
      between 0.28 and 0.95 mumol/min mg. The phospholipid dependence of the microsomal
      glutathione transferase was examined in proteoliposomes formed by cholate
      dialysis. Phosphatidyl choline, phosphatidyl serine, phosphatidyl ethanolamine,
      and rat liver microsomal phospholipids could all be used successfully to
      reconstitute the enzyme. In conclusion, microsomal glutathione transferase can
      detoxify a number of lipid peroxidation products as well as a fatty acid ozonide.
      The results imply a protective role for the enzyme under conditions of oxidative
      stress.

PMID- 7625825
TI  - Interleukin-6 down-regulates expressions of the aldolase B and albumin genes
      through a pathway involving the activation of tyrosine kinase.
AB  - Interleukin-6 plays a key role in mediating acute-phase protein synthesis in
      hepatocytes. However, the mechanism of how interleukin-6 regulates aldolase B and
      albumin syntheses in hepatocytes is not completely understood. In this study,
      using primary cultured rat hepatocytes, we have shown that interleukin-6 down
      regulates expressions of the aldolase B and albumin genes in a dose- and time
      dependent manner. We examined whether the decrease in aldolase B and albumin mRNA
      expressions by interleukin-6 reflected transcriptional down-regulation or
      stability of the mRNA. Actinomycin D and cycloheximide did not affect the
      interleukin-6-mediated decrease in the expressions of both genes. These results
      suggest that the decreased expressions of both genes induced by interleukin-6 is
      controlled at the transcriptional level, and that it is due neither to increased
      degradation of mRNA nor to synthesis of new proteins. Protein kinases play a
      fundamental role in the intracellular signal transduction. To examine the
      interleukin-6 signal pathway(s) leading to the decrease of aldolase B and albumin
      mRNA expressions, we tested various kinds of protein kinase inhibitors in this
      system. Herbimycin A, an inhibitor of tyrosine kinase(s), prevented the decrease
      in the expression of aldolase B and albumin mRNAs by interleukin-6. H-7, an
      inhibitor of protein kinase C, prevented the decrease in the expression of
      albumin mRNA by interleukin-6, but did not induce recovery of that of aldolase B
      mRNA. These results suggest that a tyrosine kinase(s) or a herbimycin A-sensitive
      kinase(s) constitutes a common pathway for interleukin-6-mediated reduction of
      aldolase B and albumin mRNA expressions and that distinct pathways exist for the
      modes of expression of the two mRNAs.

PMID- 7625827
TI  - Human oligosaccharyltransferase: isolation, characterization, and the complete
      amino acid sequence of 50-kDa subunit.
AB  - Oligosaccharyltransferase (OT) catalyzes the glycosylation of asparagine residues
      in nascent polypeptides in the endoplasmic reticulum. In a previous communication
      we reported the purification and characterization of this enzyme from chicken
      oviduct. Here we describe the purification and sequence analysis of OT from human
      liver microsomes. Oligosaccharyltransferase copurified with three proteins
      designated 50-kDa, 65-I and 65-II based on their molecular weights by gel
      electrophoresis. The N-terminal sequence of the 50-kDa component was homologous
      to the 50-kDa subunit of avian OT. The N-terminal sequences of 65-I and 65-II
      were identical to the primary structures of human ribophorins I and II,
      respectively, predicted by cDNA sequencing. The complete amino acid sequence of
      the 50-kDa subunit of human OT was determined by chemical sequencing of peptides
      isolated from chemical and enzymatic digests. The 50-kDa subunit of human OT is
      98% identical to its canine homolog, 93% identical to its avian homolog, and 25%
      identical to the beta subunit of yeast OT. These data indicate that structural
      features of oligosaccharyltransferase are conserved in all eukaryotes.

PMID- 7625828
TI  - Structural characterization by nuclear magnetic resonance spectroscopy of a
      genetically engineered high-affinity calmodulin-binding peptide derived from
      Bordetella pertussis adenylate cyclase.
AB  - This paper reports the solution conformation of a peptide (P196-267) derived from
      the calmodulin-binding domain of Bordetella pertussis adenylate cyclase. P196-267
      corresponding to the protein fragment situated between amino acid residues 196
      267 was overproduced by a recombinant Escherichia coli strain. Its affinity for
      calmodulin is only one order of magnitude lower (Kd = 2.4 nM) than that of the
      whole bacterial enzyme (Kd = 0.2 nM). The proton resonances of the NMR spectra of
      P196-267 were assigned using homonuclear two-dimensional techniques (double
      quantum-filtered J-correlated spectroscopy, total correlation spectroscopy, and
      nuclear Overhauser enhancement spectroscopy) and a standard assignment procedure.
      Analysis of the nuclear Overhauser effect connectivities and the secondary shift
      distribution of C alpha protons along the sequence allowed us to identify the
      elements of regular secondary structure. The peptide is flexible in solution,
      being in equilibrium between random coil and helical structures. Two segments of
      11 amino acids (situated between V215 and A225) and 15 amino acids (situated
      between L233 and A247) populate in a significant proportion the helix
      conformational state. The two helices can be considerably stabilized in a mixed
      solvent, trifluoroethanol/water (30/70), suggesting that the corresponding
      fragment in the intact protein assumes a similar secondary conformation. No
      elements of tertiary structure organization were detected by the present
      experiments. The conformational properties of the isolated calmodulin target
      fragment are discussed in relation with the available NMR and X-ray data on
      various peptides complexed to calmodulin.

PMID- 7625829
TI  - Modulation of Ca2+ sensitivity in smooth muscle by genistein and protein tyrosine
      phosphorylation.
AB  - Genistein, a potent tyrosine kinase inhibitor, inhibits contraction of several
      types of smooth muscle, suggesting that protein tyrosine phosphorylation may be
      an important regulatory mechanism for smooth muscle contraction. We suspected
      that one site between activation of smooth muscle and contraction which might be
      modulated by protein tyrosine phosphorylation involved mechanisms for control of
      Ca2+ sensitivity. Since smooth muscle permeabilized with staphylococcal alpha
      toxin permits direct assessment of agonist-induced Ca2+ sensitivity, we studied
      the effects of genistein on potential coupling between tyrosine phosphorylation
      and Ca2+ sensitivity in permeabilized ileal smooth muscle. Results show that
      contraction of intact preparations with carbachol is markedly and reversibly
      inhibited by 40% at 4 micrograms genistein/ml and by 60% at 20 micrograms
      genistein/ml. Permeabilized preparations that are contracted with a submaximal
      [Ca2+] in the presence of GTP relax when genistein is added to the medium.
      Genistein also reversibly inhibits contractions induced in permeabilized muscle
      with either a submaximal or maximal [Ca2+] in the presence of GTP, as well as
      receptor-coupled activation of Ca2+ sensitization with 10 microM carbachol/10
      microM GTP. Activation of permeabilized preparations at pCa 4.6 in the presence
      of 100 microM GTP promotes time-dependent tyrosine phosphorylation of several
      substrates. Both phosphorylation and force are inhibited by genistein. However,
      relatively high levels of myosin light chain phosphorylation persist during
      genistein-induced inhibition of Ca2+ sensitivity. In contrast, genistein has no
      effect on Ca(2+)-activated contraction in Triton-skinned preparations in either
      the presence or the absence of GTP. This shows that it does not directly inhibit
      actin-myosin interaction and suggests that its target(s) may be a cytosolic or
      membrane-bound regulatory protein(s) that is leached from the preparations during
      Triton-skinning. Taken together, these new data suggest that (a) tyrosine
      phosphorylation of one or more substrates may be coupled to mechanisms which
      regulate Ca2+ sensitivity and (b) the inhibitory effects of genistein are
      probably due to inhibition of agonist-induced Ca2+ sensitivity.

PMID- 7625830
TI  - Reductions catalyzed by a quinone and peroxidases from Phanerochaete
      chrysosporium.
AB  - A quinone produced from veratryl alcohol by lignin peroxidase from the white rot
      fungus Phanerochaete chrysosporium was tested for its ability to mediate
      reduction. The quinone (2-hydroxymethyl-5-methoxy-1,4-benzoquinone), reduced
      chemically or by cellobiose:quinone reductase isolated from cultures of the
      fungus, mediated the reduction of cytochrome c in reactions containing either
      Mn(III), a manganese-dependent peroxidase, Mn(II) and H2O2, or lignin peroxidase
      and H2O2. Formation of the semiquinone, the species responsible for reducing
      cytochrome c, was observed by electron spin resonance spectroscopy in these
      reactions. The production of the quinone was observed in the extracellular
      fraction of cultures grown under nutrient nitrogen-deficient conditions (2.4 mM
      ammonium tartrate) for over 10 days, starting on Day 2, but not under nutrient
      nitrogen-sufficient conditions. These results suggest that a quinone produced by
      lignin peroxidase can serve as a physiological mediator of reductive reactions
      catalyzed by the fungal peroxidases.

PMID- 7625831
TI  - Activation of glycine decarboxylase in pea leaf mitochondria by ATP.
AB  - Activity of glycine decarboxylase decreased by 60-70% after the isolated pea leaf
      mitochondria were aged for 5 h in the absence of glycine and was completely lost
      after 24 h. The reverse reaction, i.e., production of glycine from serine,
      ammonium, dihydrolipoate, and bicarbonate, was also inhibited in these aged
      mitochondria. Glycine decarboxylase could be reactivated by both exogenous and
      endogenous ATP. The latter was formed during the oxidation of succinate, malate,
      or oxoglutarate. Glycine decarboxylase consists of four subunits (P-, H-, L-, and
      T-proteins). The aged mitochondria were able to catalyze the exchange of [14C]
      bicarbonate-glycine and the oxidation of dihydrolipoate, indicating the
      persistence of P-, H-, and L-protein activities. Serine hydroxymethyltransferase
      catalyzes the formation of serine from methylene tetrahydrofolate and another
      glycine and molecule at the last reaction of glycine oxidation. The aged
      mitochondria were able to catalyze the formation of methylene tetrahydrofolate
      from [14C]serine and its reverse reaction. Therefore, it was concluded that the
      loss of glycine decarboxylase activity was due to an inhibition of the reaction
      catalyzed by T-protein, which required ATP for its activation.

PMID- 7625832
TI  - Monoterpene synthases from gymnosperms and angiosperms: stereospecificity and
      inactivation by cysteinyl- and arginyl-directed modifying reagents.
AB  - To further define specific structural and mechanistic differences among
      monoterpene synthases from divergent plant sources, the stereospecificity of the
      enzyme-catalyzed isomerization of geranyl pyrophosphate to linalyl pyrophosphate
      and the subsequent cyclization to monoterpene olefins (which have been well
      established for monoterpene synthases from herbaceous angiosperms) were examined
      for monoterpene synthases from a conifer, lodgepole pine (Pinus contorta). The
      chiral monoterpenes isolated from lodgepole pine oleoresin and the major chiral
      products from cell-free assays of each of the four lodgepole pine monoterpene
      synthases belonged to the stereochemical family related by the biosynthetic
      intermediacy of 3S-linalyl pyrophosphate. Furthermore, both the putative
      intermediate, 3S-linalyl pyrophosphate, and the natural substrate, geranyl
      pyrophosphate, were enzymatically converted to the same monoterpene enantiomers.
      Thus, like monoterpene synthases from herbaceous angiosperms, monoterpene
      synthases from lodgepole pine appear to catalyze both the stereospecific
      isomerization of geranyl pyrophosphate to linalyl pyrophosphate and the
      subsequent cyclization of this enzyme-bound intermediate to multiple,
      stereochemically related monoterpene olefin isomers. The susceptibility of
      monoterpene synthases to inactivation by cysteinyl- and arginyl-directed chemical
      modification reagents was also examined to identify specific structural
      differences between enzymes from conifers and angiosperms. Like monoterpene
      synthases from peppermint (Mentha x piperita) and culinary sage (Salvia
      officinalis), monoterpene synthases from lodgepole pine were inactivated by thiol
      directed reagents; however, unlike monoterpene synthases from these herbaceous
      angiosperms, monoterpene synthases from lodgepole pine were not protected against
      inactivation by coincubation with substrate and metal ion cofactor. Lodgepole
      pine monoterpene synthases were also inactivated by the arginyl-directed reagent
      phenylglyoxal, and coincubation with substrate and cofactor, to effect active
      site protection, reduced the rate of inactivation 10-fold. (+)-Pinene synthase
      and (-)-pinene synthase from sage were also inactivated by phenylglyoxal, but no
      protection was afforded by coincubation with substrate and cofactor. Thus,
      monoterpene synthases of conifers appear to have catalytically important arginyl
      residues specifically located at or near the active site and have at least some
      catalytically important thiol residues at a non-substrate-protectable region of
      the enzyme, in contrast to monoterpene synthases from angiosperms which appear to
      have catalytically important cysteinyl residues at the active site and have
      catalytically important arginyl residues located at a non-substrate-protectable
      region of the enzyme.

PMID- 7625833
TI  - The amino acid sequence of Rhodobacter sphaeroides dimethyl sulfoxide reductase.
AB  - The complete amino acid sequence of the soluble, monomeric molybdenum-containing
      enzyme dimethyl sulfoxide reductase from Rhodobacter sphaeroides f sp.
      denitrificans has been determined using a combination of gas-phase Edman
      sequencing of isolated peptides and direct sequencing of PCR products generated
      from R. sphaeroides genomic DNA. The protein comprises 777 residues corresponding
      to an apoenzyme molecular weight of 84,748 Da. The amino acid sequence was rich
      in Ala and Gly residues which represented 21% of the protein's composition. The
      DNA sequence was 67% rich in G and C nucleotides. The amino acid sequence
      contained 10 cysteine residues which were relatively evenly distributed
      throughout the sequence and featured regions of sequence corresponding to the
      prokaryotic molybdopterin-binding signatures 2 and 3. While exhibiting limited
      sequence similarity to the corresponding membrane-bound molybdenum-containing
      subunit (DmsA) of Escherichia coli dimethyl sulfoxide reductase, the Rhodobacter
      sequence showed extensive sequence similarity to that of the E. coli
      molybdoprotein, trimethylamine N-oxide reductase (torA). Comparison with other
      related prokaryotic molybdenum-containing enzymes indicated the presence of two
      highly conserved cysteine residues (Cys-268 and Cys-616) which may function in
      molybdenum coordination.

PMID- 7625834
TI  - The role of cyanide in the removal of type 2 copper from laccase.
AB  - We have improved a method for the removal of the type 2 copper from tree laccase
      under anaerobic reducing conditions and developed a mechanistic model. We
      identify two key steps in the reaction: (i) dissociation of copper(I) catalyzed
      by trace levels of cyanide in a weakly acidic medium and (ii) sequestration of
      the released metal by an appropriate chelator such as 2,9-dimethyl-1,10
      phenanthroline. We maintain a steady-state concentration of cyanide in a pH 5.5
      acetate buffer under a constantly exchanging nitrogen atmosphere by introducing a
      cyanometalate ion as a cofactor or by continuously injecting the ion into the
      protein solution. The type 2-depleted product is identical to previous
      preparations as regards its spectral properties, activity level and ability to
      recombine with copper(I). The mechanistic insights appear to be quite general and
      should form the basis for the development of methods for removing the type 2
      copper from other related systems.

PMID- 7625835
TI  - The effect of N-bromosuccinimide on ferredoxin:NADP+ oxidoreductase.
AB  - Treatment of spinach leaf ferredoxin:NADP+ oxidoreductase (FNR) with N
      bromosuccinimide (NBS), under conditions where approximately one tryptophan
      residue per enzyme was modified, resulted in a loss of between 80 and 85% of the
      activity of the enzyme when electron transfer from NADPH to either ferredoxin or
      2,6-dichlorophenol-indophenol was measured. Amino acid analysis revealed no
      detectable modification by NBS of any FNR amino acids other than tryptophan.
      Complex formation with ferredoxin, but not with NADP+, prevented both the
      inhibition of activity and the modification of tryptophan caused by the treatment
      with NBS. Modification of one FNR tryptophan residue had no significant effect on
      the Km values of the enzyme for either ferredoxin or NADPH or on the binding
      constants for the FNR complexes with either ferredoxin or NADP+. NBS treatment
      had only very small effects on the absorbance and circular dichroism spectra of
      FNR and did not significantly affect either the oxidation-reduction midpoint
      potential of the FAD prosthetic group of the enzyme or inhibit the reduction of
      the FAD group by NADPH. These results raise the possibility that a tryptophan
      residue may play a role in the electron transfer between the FAD of FNR and the
      enzyme substrate, ferredoxin.

PMID- 7625836
TI  - Fatty acid discrimination and omega-hydroxylation by cytochrome P450 4A1 and a
      cytochrome P4504A1/NADPH-P450 reductase fusion protein.
AB  - The omega-hydroxylation of fatty acids by certain cytochrome P450 enzymes shows a
      degree of chain-length and regionspecificity which is remarkable in view of the
      conformational flexibility of these substrates, the strong similarity in
      properties among homologs, and the lack of polar groups (other than the carboxy
      terminus) with which to guide and strength enzyme-substrate interactions. To
      investigate the chemical basis for these features of omega-hydroxylation we
      designed and synthesized a series of lauric acid analogs and evaluated them as
      substrates and inhibitors of omega-hydroxylation catalyzed by cytochrome P4504A1
      and a cytochrome P450 4A1/NADPH-P450 reductase fusion protein. Among n-alkanoic
      acids, lauric acid was found to have the optimum chain length for the fusion
      protein, as it does for native cytochrome P450 4A1. With both enzymes, chain
      shortening caused a precipitous drop in turnover while chain lengthening caused a
      gradual drop in turnover. The fusion protein omega-hydroxylated methyl laurate
      and lauryl alcohol about 1/10th as efficiently as lauric acid, but it did not
      hydroxylate lauramide. 10-Methoxydecanoic acid underwent O-demethylation (via
      omega-hydroxylation). The branched substrate 11-methyllauric acid was
      hydroxylated efficiently and selectively at the omega-position. In contrast, the
      cyclopropyl analog 11,12-methanolauric acid was not detectably hydroxylated,
      although it induced Type I binding spectrum and inhibited lauric acid omega
      hydroxylation by 43% at equimolar concentrations. omega-(Imidazolyl)-decanoic
      acid induced a Type II heme-binding spectrum and was an especially potent
      inhibitor of lauric acid hydroxylation. Collectively these data suggest that the
      active site of cytochrome P450 4A1 has an elongated tubular shape of definite
      length (ca. 14 A) with a recognition site for polar groups (including but not
      limited to carboxyl) at its entrance and the (oxo)heme group at its terminus.

PMID- 7625837
TI  - Immunoaffinity purification of DNA polymerase delta.
AB  - A monoclonal antibody against human DNA polymerase delta (pol delta) was isolated
      with properties suitable for its utilization for immunoaffinity chromatography.
      The antibody was immobilized after periodate oxidation and coupled to a hydrazide
      activated support. Starting from a partially purified preparation, calf thymus
      pol delta was purified about 200-fold in a single step. Further purification on
      ssDNA-cellulose resulted in isolation of a homogeneous preparation. The amount of
      enzyme isolated, ca. 0.3 mg of pure pol delta from 0.75 kg of calf thymus, is
      about 15-fold greater than can be achieved by conventional procedures. This
      procedure provides a significant advance in the isolation of pol delta in
      allowing its facile isolation from tissues in good yield. The isolated enzyme
      consisted of two subunits of 125 and 50 kDa. Characterization of the enzyme
      showed that these two subunits remained associated on glycerol gradient
      ultracentrifugation even in the presence of 2.8 M urea.

PMID- 7625838
TI  - 3-Hexaprenyl-4-hydroxybenzoic acid forms a predominant intermediate pool in
      ubiquinone biosynthesis in Saccharomyces cerevisiae.
AB  - The biosynthesis of ubiquinone (coenzyme Q) was studied in Saccharomyces
      cerevisiae. Lipid extracts were prepared from wild-type yeast grown in the
      presence of p-[U-14C]- and p-[carboxy-14C]hydroxybenzoic acid. Ergosterol was
      removed by adsorption to digitonin-celite, and radiolabeled lipids were purified
      by sequential reverse-phase and normal-phase HPLC steps. Radiolabeled peaks were
      identified by comparison with synthetic standards using retention time and
      electron ionization mass spectrometric criteria. The recovery and identification
      of the unstable 3-hexaprenyl-4-hydroxybenzoic acid molecule were facilitated by
      treatment of the lipid extract with diazomethane under conditions that resulted
      in the formation of the stable derivatives methyl 3-hexaprenyl-4-hydroxybenzoate
      or methyl 3-hexaprenyl-4-methoxybenzoate. In stationary-phase yeast cultures, the
      major radioactive lipid products are coenzyme Q and 3-hexaprenyl-4-hydroxybenzoic
      acid, constituting 62 and 38% of the radioactive lipids, respectively. However,
      under log-phase growth conditions the biosynthetic intermediate 3-hexaprenyl-4
      hydroxybenzoic acid predominates (accounting for 81% of the radioactive lipids).
      The data indicate that in wild-type yeast, 3-hexaprenyl-4-hydroxybenzoic acid
      forms a predominant intermediate pool in ubiquinone biosynthesis and that in log
      phase growth this ubiquinone intermediate is present at fourfold higher abundance
      than the end product. The physiological rationale for this high concentration of
      a membrane-bound intermediate is unclear.

PMID- 7625839
TI  - Carbonic anhydrase IV: role of removal of C-terminal domain in
      glycosylphosphatidylinositol anchoring and realization of enzyme activity.
AB  - Carbonic anhydrase IV (CA IV) is a glycosylphosphatidylinositol (GPI)-anchored
      membrane protein expressed on the plasma membrane of specific epithelial and
      endothelial cells. The human cDNA encodes a 312-amino-acid precursor which
      includes an NH2-terminal signal sequence (residues -18 to -1) that is removed and
      a C-terminal hydrophobic domain which is cleaved to permit transfer to the GPI
      anchor. Using biochemical methods, we established that Ser266 is the site of
      attachment of the GPI anchor to CA IV from human lung. Based on this result, we
      constructed missense mutants S266F and G267F and a truncation mutant, G267X, and
      investigated the role of removal of the C-terminal hydrophobic domain on the
      synthesis and processing of CA IV in transfected COS cells. The G267F mutation
      had no effect on CA IV expression. By contrast, the S266F mutation prevented
      removal of the C-terminal domain and the S266F CA IV was inactive, not GPI
      anchored, and not expressed on the cell surface. The G267X C-terminal deletion
      mutation resulted in secretion of an amount of CA IV severalfold higher than the
      amounts found in cells transfected with wild type cDNA. These results demonstrate
      that removal of the C-terminal hydrophobic domain is necessary both for GPI
      anchoring and for realization of CA IV activity. They further show that bypassing
      C-terminal processing by deletion of the hydrophobic domain leads to secretion of
      a fully active CA IV in amounts far greater than those which accumulate in cells
      expressing the wild type, GPI-anchored CA IV.

PMID- 7625840
TI  - Simultaneous expression of human CYP3A7 and N-acetyltransferase in Chinese
      hamster CHL cells results in high cytotoxicity for carcinogenic heterocyclic
      amines.
AB  - To investigate whether several food-derived heterocyclic amines are activated to
      genotoxic products in human fetal livers, cell lines stably expressing CYP3A7, a
      human fetus-specific form of cytochrome P450, NADPH-cytochrome P450 reductase,
      and human monomorphic or polymorphic N-acetyltransferase (NAT1 or NAT2) were
      established. The expression of CYP3A7 mRNAs and proteins was determined by RNA
      blot and immunoblot analyses, respectively. The introduction of CYP3A7 cDNA to CR
      68 cells which had been transfected with guinea pig NADPH-cytochrome P450
      reductase, NAT1, or NAT2 cDNA resulted in increased sensitivity of the cells to
      aflatoxin B1 compared to parental cells. The cytotoxicity assay for 2-amino-3
      methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline
      (MeIQ), and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) showed that 7P
      145 cells, which expressed the reductase, CYP3A7, and NAT2, were approximately 4
      , 30-, and 14-fold more sensitive to respective IQ, MeIQ, and MeIQx than parental
      CR-68 cells. There were no clear differences in sensitivity to these compounds
      among CHL, CR-68, and the cells which expressed the reductase and CYP3A7 (7R-54),
      the reductase and NAT1 (CNM-4), the reductase and NAT2 (CNP-40), and the
      reductase, NAT1, and CYP3A7 (7M-124). From these results, it was suggested that
      both CYP3A7 and polymorphic NAT2 are required for mutagenic activation of several
      heterocyclic amines in human fetal livers.

PMID- 7625841
TI  - High-pressure-induced transitions in microsomal cytochrome P450 2B4 in solution:
      evidence for conformational inhomogeneity in the oligomers.
AB  - Pressure-induced changes in ferric P450 2B4 (LM2) were studied as a function of
      benzphetamine concentration (0.05 divided by 2 mM) and state of aggregation of
      the hemoprotein in solution. Application of factor analysis to the spectral
      changes in the Soret region allowed us to resolve two particular pressure-induced
      processes in 2B4 oligomers. The first process was identified as the conversion of
      the low-spin P450 into the P420 state. At 25 degrees C it was followed by decay
      (bleaching) of about 50% of the newly formed P420. The second process was a
      pressure-induced high- to low-spin shift. Both transitions were reversible,
      except the hemoprotein bleaching. The amplitude of the P450-->P420 transition
      accounted for 67 +/- 5% of the total hemoprotein content. Furthermore, the
      fraction of the hemoprotein exposed to spin equilibrium was not affected by the
      P450-->P420 conversion and was estimated to be only about 31 +/- 5% of the total
      hemoprotein content. After the dissociation of the oligomers by 0.2% Triton N
      101, the inhomogeneity vanished: 95% of the monomers were involved in the P450-
      >P420 transition (delta V degrees = -86 ml/mol) followed by intense bleaching of
      the hemoprotein. This agrees with our earlier observations on the reduced
      carbonyl complex of P450 2B4 and suggests some conformational difference between
      subunits in P450 LM2 oligomers. The parameters of the P450-->P420 conversion
      (delta V degrees = -32 ml/mol, P1/2 = 1560 bar) show no dependency on the
      substrate concentration. Analysis of the pressure-induced spin shift versus
      benzphetamine concentration shows this transition to be caused mainly by changes
      in the spin equilibrium of both substrate-bound (delta V degrees = -49 ml/mol)
      and substrate-free (delta V degrees = -21 ml/mol) hemoprotein, whereas the
      substrate binding step itself has a very weak pressure dependency (delta V
      degrees = -8 ml/mol).

PMID- 7625842
TI  - Kinetic mechanism and divalent metal activation of human erythrocyte pyridoxal
      phosphatase.
AB  - Human erythrocyte pyridoxal phosphatase has an essential requirement for divalent
      cations. Its activation by Mg2+, Co2+, Ni2+, or Mn2+ followed Michaelis-Menten
      kinetics. Other divalent cations inhibited the enzyme. The kinetic properties of
      the enzyme were investigated with pyridoxal phosphate and Mg2+ alone and in the
      presence of the product, Pi, or dead-end inhibitors at pH 7.4 and 37 degrees C.
      The enzyme bound both the substrate and Mg2+ before products were released. Pi
      gave competitive inhibition vs substrate and noncompetitive inhibition vs Mg2+.
      Molybdate also was a competitive inhibitor vs substrate and noncompetitive
      inhibitor vs Mg2+. Ca2+ gave competitive inhibition vs Mg2+ and noncompetitive
      inhibition vs substrate. The effects of Mg2+ and substrate on the inactivation of
      pyridoxal phosphatase by a variety of group-specific reagents were studied. The
      inactivation of the enzyme by iodoacetate was potentiated by MgCl2. The Kd of the
      enzyme-Mg complex determined in the inactivation analysis was similar to the Km
      of the free enzyme for Mg2+, indicating that Mg2+ binds to the free enzyme. Low
      concentrations of a substrate, pyridoxine phosphate, or Pi protected pyridoxal
      phosphatase from inactivation by N-ethylmaleimide in the absence or presence of
      Mg2+. Thus, the substrate binds to the free enzyme and the enzyme-Mg complex. The
      steady-state kinetics and the kinetics of inactivation are consistent with random
      binding of pyridoxal phosphate and Mg2+ and with the formation of a dead-end
      complex of Pi with the enzyme-Mg complex.

PMID- 7625843
TI  - Molecular cloning and expression of alfalfa (Medicago sativa L.) vestitone
      reductase, the penultimate enzyme in medicarpin biosynthesis.
AB  - Medicarpin, the major phytoalexin in alfalfa, is synthesized by way of the
      isoflavonoid branch of phenylpropanoid metabolism. One of the final steps of
      medicarpin biosynthesis, from vestitone to 7,2'-dihydroxy-4'-methoxyisoflavanol,
      is catalyzed by vestitone reductase. A 1245-bp cDNA clone which encodes vestitone
      reductase was identified utilizing internal amino acid sequence of purified
      vestitone reductase. When expressed in Escherichia coli, the cloned enzyme
      exhibits strict substrate stereospecificity for (3R)-vestitone, as was observed
      for vestitone reductase purified from alfalfa. The calculated molecular weight of
      the protein (35,918) is similar to that of purified vestitone reductase from
      alfalfa (38 kDa by SDS-PAGE). The levels of vestitone reductase transcript (1.35
      kb) greatly increase within 2 h of elicitor addition to alfalfa cell suspension
      cultures, preceding the rapid increases in vestitione reductase enzyme activity
      and medicarpin biosynthesis. In healthy alfalfa plants, the highest levels of
      transcripts were detected in roots and root nodules, consistent with the
      synthesis of medicarpin and its conjugate in these tissues. The cloning of the
      vestitone reductase gene provides a specific tool for the study and manipulation
      of pterocarpan biosynthesis in legumes.

PMID- 7625844
TI  - Inhibition of glycogenin-catalyzed glucosyl and xylosyl transfer by cytidine 5'
      diphosphate and related compounds.
AB  - The self-glucosylation of beef kidney glycogenin was inhibited by the following
      pyrimidine nucleotides and nucleotide sugars, listed in order of decreasing
      effectiveness: CDP-glucose, CDP, UDP-xylose, UDP-N-acetylglucosamine, UDP
      galactose, UDP, CTP, CDP-choline, UDP-glucuronic acid, beta-S-UDP-glucose, and
      CMP. In contrast, the purine nucleotide sugars, ADP-glucose and GDP-glucose, were
      essentially ineffective, as was the pyrimidine nucleoside, cytidine. UDP-Xylose
      may be utilized by glycogenin as an alternative sugar donor instead of UDP
      glucose (Roden, L., Ananth, S., Campbell, P., Manzella, S., and Meezan, E. (1994)
      J. Biol. Chem. 269, 11509-11513) and therefore presumably inhibited the glucosyl
      transfer reaction by being a competitive substrate. Like glucosyl transfer,
      xylosyl incorporation into glycogenin was also inhibited effectively by CDP. On
      the other hand, UDP-xylose:proteoglycan core protein xylosyltransferase (EC
      2.4.2.26) was not affected by CDP, nor was it inhibited by UDP-glucose. Addition
      of CDP or UDP-glucose to reaction mixtures containing both enzymes therefore made
      it possible to assay xylosyltransferase EC 2.4.2.26 reliably without the
      extensive product characterization that is otherwise necessary. The CDP effect on
      glycogenin further allowed the development of an improved procedure for the
      purification of this enzyme, in which specific elution of an affinity matrix (UDP
      glucuronic acid-agarose) was carried out with CDP as the eluant.

PMID- 7625845
TI  - Properties of a transplasma membrane redox system of Phanerochaete chrysosporium.
AB  - A transplasma membrane redox system of Phanerochaete chrysosporium was studied
      using ferricyanide, a membrane-impermeable electron acceptor. Rates of reduction
      were dependent upon initial ferricyanide concentration and mycelial mass.
      Specific activities of 12 +/- 2 nmol/min/mg mycelia (dry wt) were consistently
      obtained using nutrient-sufficient mycelia at pH 8.0 and 10 mM ferricyanide. Upon
      nutrient limitation (either carbon or nitrogen), activity decreased. Reduction
      was inhibited by carbonyl cyanide m-chloromethoxyphenyl hydrazone, 2,4
      dinitrophenol, and sodium azide but not by potassium cyanide at 100 nmol/mg
      mycelia. Ferricyanide reduction and proton export rates increased with pH above
      the physiological pH for the fungus. The stimulation in proton exported by the
      addition of ferricyanide was equal to the rate of ferricyanide reduced at pH 8.0
      when Hepes buffer was used. The relevance of these findings with regard to the
      physiological pH optimum of the fungus and the metabolism of pollutants by this
      fungus is discussed.

PMID- 7625846
TI  - Kinetic constants for the hydrolysis of aggrecan by the papaya proteinases and
      their relevance for chemonucleolysis.
AB  - The four known proteinases from papaya latex, namely papain (EC 3.4.22.2),
      chymopapain (EC 3.4.22.6), caricain (EC 3.4.22.30), and glycyl endopeptidase (EC
      3.4.22.25), were purified to homogeneity and fully characterized by single radial
      immunodiffusion and active-site titration. A modified HPLC gel permeation assay
      was used to determine the kinetic constants for aggrecan hydrolysis by the papaya
      proteinases. The disappearance of intact aggrecan monomer was first-order,
      indicating that for the four enzymes studied the Km was much larger than 0.5
      microM and that kcat/Km = 1.2 +/- 0.1 x 10(6) M-1 s-1 for chymopapain, 1.20 +/-
      0.08 x 10(6) M-1 s-1 for caricain, 0.90 +/- 0.02 x 10(6) M-1 s-1 for papain, and
      0.120 +/- 0.005 x 10(6) M-1 s-1 for glycyl endopeptidase. Chymodiactin, the
      chymopapain preparation used for chemonucleolysis, consists of a mixture of
      chymopapain (70%), caricain (20%), and glycyl endopeptidase (4%). The rate
      constant for the aggrecan hydrolysis by such a mixture was not significantly
      different from the rate constant for pure chymopapain. As a result of these
      observations, we predict that pure chymopapain could replace partially purified
      chymopapain preparations for chemonucleolysis.

PMID- 7625847
TI  - Arachidonic acid metabolism by human cytochrome P450s 2C8, 2C9, 2E1, and 1A2:
      regioselective oxygenation and evidence for a role for CYP2C enzymes in
      arachidonic acid epoxygenation in human liver microsomes.
AB  - The membrane-bound endogenous fatty acid arachidonic acid can be released from
      membranes by phospholipases and then metabolized to biologically active compounds
      by cyclooxygenases, lipoxygenases, and cytochrome P450 (CYP) enzymes. In the
      liver the CYP pathway is the most significant. Liver CYP arachidonate products
      include epoxyeicosatrienoic acids (EETs) and monohydroxylated products (HETEs).
      We examined metabolism of [1-14C]arachidonic acid by a panel of 10 human CYP
      enzymes expressed in HepG2 cells. In the absence of expressed CYP enzymes,
      control HepG2 cell microsomes generated only small amounts of omega- and omega--1
      OH arachidonic acid (ratio 2:1). Microsomes from HepG2 cells expressing CYP2C8,
      2C9, 1A2, and 2E1 were 7-21 times more active than microsomes from the HepG2
      controls. CYP2C8, 2C9, and 1A2 principally generated epoxygenase products; 36 to
      48% were in the form of EET-diols, reflecting host HepG2 microsomal epoxide
      hydrolase activity. CYP2C8 and 2C9 formed more 14,15- and 11,12-EET than did
      CYP1A2, while CYP1A2 formed more 8,9-EET. CYP2C9 also generated a peak with the
      retention time of 12-HETE. CYP2E1 generated omega--1-OH arachidonic acid and, to
      a lesser extent, omega-OH arachidonic acid (ratio 2:1). A small amount of
      epoxygenase activity was also detected for CYP2B6; its overall activity, however,
      was only about twice control levels. Activities of CYP2A6, 3A3, 3A4, and 3A5 were
      low and limited to the omega-/omega--1-OH arachidonic acid peak; CYP2D6 was
      inactive. Microsomes prepared from three individual human livers varied threefold
      in total arachidonic acid metabolism. For all three livers omega-OH arachidonic
      acid was the major product (up to 74% of total metabolites). Epoxygenase products
      constituted 14 to 28% of the total products; 60 to 83% of those were EET-diols,
      indicating that the human liver microsomes have substantial EET-epoxide hydrolase
      activity. 11,12-EET was the major EET for two livers and 14,15-EET for the third.
      The CYP2C inhibitor sulfaphenazole depressed human liver microsomal epoxygenase
      activity by 50% at 50 microM, while alpha-naphthoflavone inhibited arachidonic
      acid epoxygenase activity by 27% at 2 microM and by 32% at 10 microM.
      Collectively, these findings suggest that human liver microsomal arachidonic acid
      metabolism is catalyzed principally by CYP2C enzymes. CYP1A2, CYP2E1, and
      possibly CYP2B6 are likely to play more minor roles, though their contribution
      may be enhanced by exposure to inducers of those enzymes. CYP2A6, CYP2D6, and
      CYP3A enzymes are unlikely to make any significant contribution.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7625848
TI  - Analysis of an alternatively spliced exon of the neurofibromatosis type 1 gene in
      cultured melanocytes from patients with neurofibromatosis 1.
AB  - Neurofibromatosis type 1 (NF1) is characterized by clinical features that
      primarily affect tissues derived from the neural crest (neurofibromas, cafe
      aulait macules). Because aberrant regulation of alternative splicing in the NF1
      gene transcript may be of functional significance, cultured melanocytes from cafe
      aulait macules (CALM), as an example of benign NF1 lesions, were examined for the
      expression of the different alternative splice products of this gene. Both kinds
      of NF1 messengers (type 1 and 2) were found not only in CALM melanocytes but also
      in keratinocytes, fibroblasts and blood cells. Except in blood cells, there was a
      predominance of the type 2 transcript. Melanocytes from NF1 patients and healthy
      donors showed similar expression patterns under several culture conditions. Our
      results suggest that the development of CALM does not correlate with a switch in
      the ratio of type 1 to type 2 NF1 messenger RNA.

PMID- 7625849
TI  - Stimulated expression of decorin and the decorin gene in fibroblasts cultured
      from patients with localized scleroderma.
AB  - Decorin mRNA levels, the content of decorin and the synthesis of dermatan
      sulphate in skin fibroblasts from patients with systemic and localized
      scleroderma were investigated. Approximately a 2.2-fold increase in decorin mRNA
      levels, was found by Northern blot analysis in localized scleroderma, but no
      significant changes were found in systemic scleroderma. Decorin, as measured by
      an immunoblot assay, was increased 2.6-fold in fibroblast cultures from localized
      scleroderma but not in those from systemic scleroderma. In contrast, the
      synthesis of dermatan sulphate was similar in both conditions. These results
      indicate that altered decorin gene expression causes abnormal proteoglycan
      metabolism in localized scleroderma.

PMID- 7625850
TI  - Identification of genes specifically regulated in human melanoma cells.
AB  - In order to improve the characterization of human malignant melanoma cells and
      their variant gene expression in vitro, a search for specifically regulated genes
      was performed. Four melanoma cell lines (M5, MEWO, IGR39, SKMEL13) and newly
      cultured normal human melanocytes were included in a comparative hybridization
      (differential screening) of a human melanoma cDNA-library. Six cDNAs were
      isolated showing a stronger expression (four genes) or a weaker expression (two
      genes) in melanoma cells than in normal human melanocytes. Quantification of the
      expression patterns of the two repressed genes in Northern blots revealed general
      expression in all melanocyte cultures examined, no expression in three cell lines
      (M5, IGR39, SKMEL13) and weak expression in MEWO. The four induced genes were
      found to be only weakly expressed in normal human melanocytes, but showed an
      elevated expression in all of the four melanoma cell lines tested. Thus, using
      the technique of differential screening, consistent gene regulation at the
      messenger RNA level was identified, which distinguishes the four melanoma cell
      lines tested from normal melanocytes. We conclude from the expression patterns
      that specific gene regulation in melanoma cells in vitro is characterized both by
      strong repression of some melanocyte genes, as well as by the induction of other
      genes, but there was no indication of new expression of genes specific for
      melanoma cells. Because of the uniform induction or repression in different
      melanoma cell lines, it is conceivable that the cloned genes may be involved in
      the malignant transformation of melanocytic cells.

PMID- 7625852
TI  - Influence of aging, localization, glucocorticoids and isotretinoin on matrix
      metalloproteases 2 (MMP-2) and 9 (MMP-9) in suction blister fluids.
AB  - The expression of two matrix metalloproteases (MMPs), 72 kDa gelatinase (MMP-2)
      and 92 kDa gelatinase (MMP-9), was studied in suction blister fluids and serum
      using a zymographic method. Both of the enzymes were detectable in blister fluid
      and serum, but their expression varied. The MMP-2 levels in serum were only about
      half of the levels in blister fluid, while the level of MMP-9 was about the same
      in both serum and blister fluid. The overall level of MMP-2 in serum was much
      lower than the level of MMP-9 which was possibly derived from inflammatory cells.
      In subjects aged from 20 to 86 years, no marked changes were seen in the serum or
      blister fluid gelatinases. Interestingly, body site affected the level of MMP-9.
      The lowest level was recorded in fluid from blisters on the lower leg, in which
      the level was only about 19% of the level in fluid from blisters on the abdomen.
      The levels of MMP-2 and MMP-9 were not decreased by pharmacological doses of
      systemic prednisone or isotretinoin, which indicates that systemic glucocorticoid
      or retinoid treatment does not affect the basal levels of MMP-2 and MMP-9.

PMID- 7625853
TI  - Elevated plasma endothelin levels in systemic sclerosis.
AB  - Endothelin is a novel potent vasoconstrictor peptide produced mainly by
      endothelial cells. Thrombomodulin is a high-affinity thrombin receptor on
      vascular endothelial cells that plays an important role as a natural
      anticoagulant. In this study, we measured plasma levels of endothelin and
      thrombomodulin in patients with systemic sclerosis or Raynaud's disease. Plasma
      levels of endothelin and the ratio of thrombomodulin to creatinine were
      significantly increased in patients with systemic sclerosis compared with normal
      controls, and there was a positive correlation between these two indicators (r =
      0.615, P = 0.004). Moreover, plasma levels of endothelin were significantly
      higher in patients with diffuse systemic sclerosis than in patients with limited
      systemic sclerosis. In contrast, plasma levels of endothelin in patients with
      Raynaud's disease were not significantly increased. These results suggest that
      increased plasma levels of endothelin and thrombomodulin may reflect
      microvascular damage in systemic sclerosis.

PMID- 7625854
TI  - Susceptible responsiveness to bacterial superantigens in peripheral blood
      mononuclear cells from patients with psoriasis.
AB  - We investigated the in vitro responses to bacterial superantigens of peripheral
      blood mononuclear cells taken from patients with psoriasis (one arthropathic, two
      guttate and four chronic plaque type). We also analysed the relationship between
      the magnitude of the responses of peripheral blood mononuclear cells to bacterial
      exotoxins and the number of circulating T cells bearing V beta 2 and V beta 3
      regions. The proliferative response of peripheral blood mononuclear cells to
      Staphylococcal enterotoxin B and toxic shock syndrome toxin-1 was significantly
      higher in patients with active psoriasis than in normal subjects. An improvement
      in skin eruption was associated with a decrease in the lymphocyte response to one
      half or one-third that of the active phase. There was no significant difference
      between patients with psoriasis and normal subjects in the percentage of V beta 2
      and V beta 3-positive circulating T cells. The percentages of V beta 2-positive
      and V beta 3-positive cells were not correlated with the levels of responsiveness
      to toxic shock syndrome toxin-1 and to Staphylococcal enterotoxin B,
      respectively. These findings suggest that the magnitude of responses of
      peripheral blood mononuclear cells to bacterial toxins does not depend on the
      number of T cells reactive with the relevant superantigen, but depends on the
      extent of skin lesions in psoriasis.

PMID- 7625851
TI  - Expression of collagenase and stromelysin in skin fibroblasts from recessive
      dystrophic epidermolysis bullosa.
AB  - Collagenase and stromelysin expression in recessive dystrophic epidermolysis
      bullosa (RDEB) was studied at both the protein and the gene expression levels in
      fibroblast cultures. The amount of enzyme protein in the culture medium, as
      determined using a specific enzyme assay, showed a 9.7-fold increase in
      collagenase and a 2.7-fold increase in stromelysin in RDEB fibroblasts (n = 4
      patients) compared with controls (n = 3 subjects with normal skin). Collagenase
      activity was extremely high in all RDEB fibroblasts. Gene expression, as assessed
      by Northern blot hybridization, was increased in two sets of RDEB fibroblasts
      with respect to collagenase, and in two other sets of RDEB fibroblasts with
      respect to stromelysin. The effect of interleukin-1 alpha (IL-1 alpha) on
      metalloproteinase expression was also examined. The results revealed that: 1)
      collagenase and stromelysin expression was variably increased at both the protein
      and the gene expression levels in RDEB fibroblasts; (2) the gene expression level
      did not always reflect the corresponding protein level; and (3) IL-1 alpha
      produced a differential effect on collagenase and stromelysin expression.
      Although the causative gene for RDEB is a type VII collagen, the abnormal
      expression of collagenase and/or stromelysin is still important in considering
      the pathophysiology of RDEB.

PMID- 7625855
TI  - Ketoconazole in atopic dermatitis: therapeutic response is correlated with
      decrease in serum IgE.
AB  - The prevalence of specific IgE antibodies to the yeasts Pityrosporum orbiculare
      and Candida albicans was investigated in adult patients with atopic dermatitis
      (AD) or with seborrhoeic dermatitis and in healthy controls by means of the
      radioallergosorbent test (RAST). Of 63 AD patients, 28 (44%) had IgE antibodies
      to P. orbiculare and 21 (33%) to C. albicans. This is highly significant, since
      no antibodies were found in sera from other patients or controls. With the
      intention to treat, 20 patients with AD and a positive RAST to P. orbiculare were
      given ketoconazole 200 mg daily for 2 months and 200 mg twice weekly for further
      3 months. The clinical scores improved during treatment with a reduction in the
      levels of specific IgE to P. orbiculare and total serum IgE. However, there were
      no correlations between clinical score and serum levels of P. orbiculare-specific
      IgE. C. albicans-specific IgE, on the other hand, correlated both with clinical
      score and with total serum IgE.

PMID- 7625856
TI  - Mast cells in melanocytic tumours.
AB  - The importance of mast cells in local homeostasis, inflammation and tumour
      surveillance is supported by many studies, and the association of mast cells with
      various neoplasms has been known for a long time. The functional significance of
      mast cells surrounding tumours is currently unclear. In the present
      histopathological study, 16 naevi and 44 primary malignant melanomas were
      analysed. The follow-up time after primary surgery of malignant melanoma patients
      was almost 10 years, during which time half of the tumours had metastasized. The
      numbers of mast cells surrounding pigmented lesions were determined. The mast
      cells were visualized using a modified toluidine blue staining (pH 0.5; 24 h).
      Significantly different numbers of mast cells were found in naevi compared to
      melanomas (P = 0.0013), but no significant correlation could be identified
      regarding prognostic parameters including tumour thickness and clinical outcome.

PMID- 7625858
TI  - Visualization of diffusion pathways across the stratum corneum of native and in
      vitro-reconstructed epidermis by confocal laser scanning microscopy.
AB  - Confocal laser scanning microscopy is a technique that permits the direct
      visualization in unfixed material of diffusion pathways and the cellular
      distribution of fluorescent markers after topical applications. This approach, in
      which the tissue specimen is optically sectioned, allows the study of changes in
      distribution pattern of applied compounds depending on the vehicle, time and
      depth without the interference of chemical alterations induced by most of the
      current techniques used for such studies. Using this technique the permeability
      properties of in-vitro-reconstructed epidermis were compared with those of the
      native counterpart. The epidermis was reconstructed by culturing human adult
      keratinocytes at the air-liquid interface either on fibroblast-populated collagen
      or on de-epidermized dermis. A fluorescent probe--Nile red (NR)--was applied in
      three different vehicles--polyethylene glycol (PEG) with a molecule mass of 400
      (Da), propylene glycol (PG) and dimethyl sulphoxide (DMSO)--which perturb the SC
      barrier function to different extents. When NR was applied in PEG and PG on
      native epidermis, the amount of NR penetrating into and through the SC was very
      low, but was markedly increased when NR was applied in DMSO. Unlike native
      epidermis, the reconstructed epidermis allowed rapid NR penetration after the
      application in any of the solvents used. Furthermore, NR applied on reconstructed
      epidermis, was distributed quite homogeneously between the cellular and the
      intercellular spaces throughout the SC, suggesting that not only intercellular
      lipid structures but also the properties of the cornified envelopes differed
      markedly from those found in native epidermis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7625859
TI  - Stratum corneum dynamic function measurements after moisturizer or irritant
      application.
AB  - Two simple tests were conducted which allowed the quantification of parameters
      that characterize the stratum corneum (SC) dynamic functions in vivo under
      physiological conditions after moisturizer applications for 1 h and after
      irritation with different concentrations of sodium lauryl sulphate (SLS; 0.5-4%)
      applied under occlusion for 15 min or 24 h. Both tests, the sorption-desorption
      test (SDT) and the moisture accumulation test (MAT), were performed with a Nova
      Dermal Phase Meter 9003. The following parameters were quantified: prehydration
      state (SDT, MAT), hygroscopicity, water-holding capacity (SDT), water
      accumulation velocity and water accumulation (MAT). These procedures allowed the
      demonstration of the water-holding effect of urea contained in moisturizers.
      Differences between the long and the short application time of SLS were
      characterized by differences in SC dynamic functions while the hydration state
      was not changed. An effect on transepidermal water loss (TEWL) was noted only
      after the long application time, although the MAT clearly showed dynamic
      parameters to be changed after 15 min of treatment. These tests were simple in
      practice and allowed the demonstration of functional modifications of the SC
      while other parameters remained unchanged. They gave insight into possible action
      mechanisms of urea and SLS in the SC.

PMID- 7625860
TI  - Gene expression of retinoic acid receptors and cellular retinoic acid-binding
      proteins in rhino and hairless mouse skin.
AB  - The rhino mouse comedolytic model and the hairless mouse photoaging model are
      established animal models for screening the in vivo activity of retinoids.
      However, the expression of the retinoic acid receptors (RARs) and cellular
      retinoic acid-binding proteins (CRABPs), known to regulate retinoid activity, is
      not completely understood in these mouse mutants. For this purpose, mRNA was
      isolated from rhino and hairless mouse skin and the gene expression of the RARs
      and CRABPs was measured by Northern blot hybridization. Results showed that RAR
      gamma was the predominantly expressed RAR in both mouse strains. Two isoforms of
      RAR gamma, RAR gamma 1 and RAR gamma 2, were detected with RAR gamma 1 being the
      more strongly expressed. RAR alpha was also detected, but to a lesser degree than
      RAR gamma. RAR beta expression was not detectable by our methodology.
      Additionally, topical treatment of these mice with 0.1% all-trans-retinoic acid
      (tRA) cream resulted in no significant alteration in the expression of the RAR
      genes. By contrast, CRABP-II was induced 2-4 fold by topical tRA treatment. CRABP
      I, expressed to a lesser degree than CRABP-II, was not inducible. The relative
      expression of the RARs, CRABPs, and inducibility of CRABP-II by tRA in both rhino
      and hairless mouse skin paralleled that reported for human and mouse skin. These
      observations suggest that the altered phenotype observed in the rhino mouse most
      likely does not result from an altered expression level of these genes. The
      results also support these two animals as models for evaluating the therapeutic
      potential of retinoids.

PMID- 7625857
TI  - The effect of glycerol and humidity on desmosome degradation in stratum corneum.
AB  - Moisturizers are known to have occlusive, emollient and humectant properties, all
      of which help to alleviate the symptoms of skin xerosis. Although the biological
      mode of action of moisturizers is poorly understood, the recent observation that
      skin xerosis is associated with incomplete desmosome digestion suggests that
      moisturizers improve the desquamation process in such conditions. To examine the
      possibility that certain moisturizers act by facilitating desmosomal digestion,
      we investigated the ability of glycerol, a common humectant, to influence this
      process in stratum corneum in vitro. Examining desmosome morphology in isolated
      stratum corneum by electron microscopy, it was observed that the desmosomes were
      in more advanced stages of degradation in glycerol-treated tissue compared with
      control tissue. This enhanced desmosomal degradation in glycerol-treated tissue
      was confirmed by significant decreases in the levels of immunoreactive desmoglein
      1, a marker of desmosome integrity. Desmosomal degradation was also shown to be a
      humidity-dependent event, being significantly reduced at low relative humidity.
      The effect of glycerol on desmosome digestion was emphasized further in two in
      vitro model systems. Firstly, glycerol increased the rate of corneocyte loss from
      the superficial surface of human skin biopsies in a simple desquamation assay.
      Secondly, measurement of the mechanical strength of sheets of stratum corneum,
      using an extensiometer, indicated a dramatic reduction in the intercorneocyte
      forces following glycerol treatment. These studies demonstrated the ability of
      glycerol to facilitate desmosome digestion in vitro. Extrapolating from these
      results, we believe that one of the major actions of moisturizers in vivo is to
      aid the digestion of desmosomes which are abnormally retained in the superficial
      layers of xerotic stratum corneum.

PMID- 7625862
TI  - Effects of adult T-cell leukaemia-derived factor on ultraviolet radiation-induced
      skin injury.

PMID- 7625863
TI  - The psoriasis-associated antigen, pso p27, is expressed by tryptase-positive
      cells in psoriatic lesions.

PMID- 7625864
TI  - Proliferative activity of keratinocytes correlates with that of melanocytes in
      naevi and melanomas.

PMID- 7625861
TI  - Stimulation of elastin expression by minoxidil in chick skin fibroblasts.
AB  - Minoxidil inhibited the proliferation of embryonic skin fibroblasts during the
      growth phase but not during the stationary phase. Minoxidil stimulated elastin
      synthesis two-fold in a dose-dependent manner at a concentration of 1 mM during
      the stationary phase. The stimulation of elastin synthesis paralleled a
      comparable increase in elastin mRNA level. These results suggest that the
      stimulation of elastin expression by minoxidil in skin fibroblasts was controlled
      at the elastin mRNA level and also suggest that its elastin-stimulating effect is
      not related to the suppressive effect on cell proliferation. Minoxidil appears to
      be a potent stimulator for elastin expression in skin fibroblasts.

PMID- 7625865
TI  - Type IV collagenase in squamous cell and basal cell skin carcinomas.

PMID- 7625866
TI  - Boundaries.

PMID- 7625867
TI  - Dimensions of response to antidepressant agents in bulimia nervosa: a review.
AB  - Many patients suffering from bulimia nervosa benefit from treatment with
      antidepressant medication. Nurses, like other mental health clinicians, tend to
      assess the effectiveness of a pharmacologic agent in patients with bulimia
      nervosa by the decline in the frequency of binge eating episodes. Clinical
      descriptions and research reports suggest the possibility of additional
      behavioral dimensions of treatment responsiveness, although the extent to which
      associated behaviors or symptoms improve is not well documented. This paper
      examines 16 placebo-controlled pharmacological trials in patients with bulimia
      nervosa to evaluate a range of potential measures of response to antidepressant
      intervention.

PMID- 7625868
TI  - Striving for stability with bipolar disorder despite barriers.
AB  - A conceptual model was developed during interviews with 33 participants that
      depicts the processes of information search and self-management of hospitalized
      people with bipolar disorder. Grounded theory methodology guided data collection
      and analysis. Barriers were reported as encountered throughout the processes;
      denial of the disorder was the most prevalent obstacle. Critical areas of
      intervention are helping the person accept the disorder and achieving the basis
      to be motivated for self-management. Recommendations are for relapse reduction
      programs to be structured on the awareness that relapse is most likely to occur
      when barriers are encountered, and that people with the disorder perceive
      barriers to be everywhere.

PMID- 7625869
TI  - Mental illness in late life: the neurobiology of depression.
AB  - The majority of elderly adults negotiate late life free from significant
      psychological disability. However, depression is one of the most common and
      distressing mental health problems they face. A number of factors associated with
      mental health, illness and depression in older adults is reviewed. In addition,
      an overview of selected psychological and biological theories related to
      depression are presented with the focus on genetic studies and the neurobiologic
      nature of stress to demonstrate the interaction between brain, behavior,
      cognition, and emotion. Psychiatric mental health nurses are challenged not only
      to examine the complex interaction between physical, mental, and social factors,
      but to integrate this knowledge into the discipline of psychiatric-mental health
      nursing, its practice, research, and education.

PMID- 7625870
TI  - The impact of childhood sexual abuse on the psychological well-being and practice
      of nurses.
AB  - This study compares the psychological well-being of nurses who were sexually
      abused as children with those who were not abused and considers the impact of
      this abuse on aspects of their clinical practice. On the psychological measures,
      abused nurses differed from the nonabused nurses by having significantly higher
      distress scores and lower self-esteem scores. For some nurses, the abuse
      influenced their private and professional relationships including personal sexual
      relationships and working with other health professionals. These results
      highlight the need for the educational and health care systems to consider the
      needs of health care professionals who may have been abused.

PMID- 7625871
TI  - Inquiring about childhood sexual abuse as part of the nursing history: opinions
      of abused and nonabused nurses.
AB  - This article explores the opinions of nurses who were sexually abused as children
      and those who were not, concerning routine inquiry about a history of sexual
      abuse. Approximately 60% of the participants indicated that routine inquiry
      should be conducted in pediatric and psychiatric settings. Reasons put forward
      for not inquiring included concerns about being intrusive, feeling unqualified to
      deal with content if abuse had occurred, and fear of increasing the distress of
      clients. Participants believed nurses needed education in this area if they were
      to be effective. Reasons why this topic involving sexuality and violence may be
      difficult for nurses are considered.

PMID- 7625872
TI  - Components of an effective transitional residential program for homeless mentally
      ill clients.
AB  - Review of clinical records of 228 former clients of a Transitional Residential
      PROGRAM for severely, persistently mental ill homeless persons was conducted to
      examine PROGRAM results for completers and noncompleters. Of the 228 clients, 110
      (48.3%) completed the PROGRAM: they became psychiatrically stabilized, found
      secure housing, and began receiving disability pensions. Completers participated
      in significantly more activities than noncompleters. Psychiatric diagnosis was
      unrelated to successful PROGRAM completion. Individuals who left against advice
      had significantly fewer previous hospitalizations.

PMID- 7625873
TI  - Toward an interactional model of suicidal behaviors: cognitive rigidity,
      attributional style, stress, hopelessness, and depression.
AB  - This paper explores major theoretical models and research findings regarding the
      interaction of selected cognitive factors, such as cognitive rigidity and
      attributional style, stress, hopelessness, and depression. Toward the prediction
      of suicidal behaviors, two models are synthesized: a cognitive rigidity/stress
      diathesis-hopelessness model, and a pluralistic, interactional model. In
      addition, relevant nursing prevention and intervention strategies from a
      cognitive therapy framework are discussed, as well as implications for nursing
      research.

PMID- 7625874
TI  - Increase of intracellular free [Ca2+] in single human motile spermatozoa treated
      with human follicular fluid.
AB  - The intracellular free [Ca2+] concentration ([Ca2+]i) in individual human sperm
      was measured using a fluorescent Ca2+ indicator. In 18 of 23 motile sperm
      (78.3%), [Ca2+]i increased significantly and promptly after addition of 20% human
      follicular fluid (hFF), but in the others it did not increase. The mean resting
      [Ca2+]i level of sperm in which [Ca2+]i increased after addition of 20% hFF (the
      influx group) was significantly lower than those in which it did not increase
      (112.8 +/- 40.1 nM vs. 156.9 +/- 13.5 nM, p < .05). After addition of 20% hFF,
      the mean [Ca2+]i in the influx group reached a peak value of 210.7 +/- 24.7 nM
      within 30 s and then decreased slowly; the mean [Ca2+]i values 1, 5, 10, and 15
      min after addition of 20% hFF were 179.3 +/- 31.4, 174.3 +/- 30.2, 172.5 +/-
      27.8, and 175.1 +/- 27.2 nM, and all values were significantly higher than the
      resting level (p < .01). The frequency distribution of [Ca2+]i after addition of
      20% hFF was shifted toward higher concentrations (p < .01). However, the addition
      of 20% hFF did not increase the percentage of live acrosome reaction (before 3.8
      +/- 0.9% vs. after 2.9 +/- 0.5%, respectively). Thus, hFF increased [Ca2+]i in
      about 80% of the motile sperm. Relatively high [Ca2+]i levels persisted for at
      least 10-15 min after its addition. However, hFF did not trigger a rapid response
      in acrosome reaction.

PMID- 7625875
TI  - Analysis of semen in a constantly changing social context of medicine.
AB  - Semen analysis is one of the most valuable diagnostic methods that play a
      critical role in andrology. The introduction of computer-assisted methods of
      human semen analysis [6], in vitro fertilization, and other auxiliary
      methodologies [4] has greatly enhanced the expectations of infertile couples in
      having a baby. However, routine semen analysis plays a significant role in an
      infertility clinic, particularly in developing countries. Standardization of
      routine semen analysis therefore becomes the key issue in laboratories involved
      in such analysis. Apart from that, semen analyses carried out in different
      populations bring out the changing pattern of semen quality due possibly to the
      influences of factors like lifestyle, race, population dynamics, and culture. It
      also helps to set standards of semen quality in the changing context of medicine.

PMID- 7625876
TI  - Interlaboratory interprotocol comparison of indirect immunobead assay for sperm
      associated antibodies in serum.
AB  - This investigation was designed to study the effect of two different protocols on
      the indirect sperm-associated antibody test on serum performed using Bio-Rad
      immunobead (IBT) at two andrology laboratories. Aliquots of 31 serum samples from
      infertile couples were analyzed by both protocols. The IBT was negative by both
      protocols (100% concordance) for 18 serum samples. Seven of the 13 remaining
      samples were positive by both protocols (> or = 10% bead attachment by protocol A
      and > or = 20% bead attachment by protocol B), for a concordance of 54%. The
      remaining six samples were positive by one of the two protocols. The overall
      concordance for positive and negative results was 81% (25 of 31 samples).
      Protocol A detected a higher percentage of bead attachments for IgG and IgA,
      while protocol B detected a higher percentage of bead attachments for IgM. The
      discordance in the results of IgA attachment obtained by the two protocols was
      statistically significant (p < .05). A standardized, uniform protocol for the
      indirect IBT is needed.

PMID- 7625878
TI  - Magnolol protects human sperm motility against lipid peroxidation: a sperm head
      fixation method.
AB  - It was previously reported that magnolol, isolated from the Chinese medicinal
      herb Magnolia officinalis, had a potent inhibitory activity on lipid
      peroxidation. Since sperm motility could be suppressed by lipid peroxidation,
      this study examines the protective effect of magnolol on lipid peroxidation
      suppressed sperm motility. FeSO4 was used to induced lipid peroxidation and sperm
      motility was expressed as tail beat frequency (TBF) measured with a sperm head
      fixation method. Magnolol at 10(-9) to 10(-7) M significantly reversed the FeSO4
      suppressed TBF. Magnolol significantly inhibited the generation of
      malondialdehyde (MDA), the end product of lipid peroxidation, in sperm. Magnolol
      protected sperm motility by inhibiting lipid peroxidation in sperm.

PMID- 7625877
TI  - Bovine seminal plasma contains factors that enhance lymphocyte transformation in
      vitro.
AB  - The important immunosuppressive properties of seminal plasma have significant
      functions in the processes of reproduction. They mask the presence of an
      immunostimulating activity. From bovine seminal plasma two active factors have
      been isolated and characterized with marked enhancing activity for in vitro PHA
      dependent lymphocyte transformation. They have inosine and hypoxanthine
      structures, as confirmed by UV absorption profiles, TLC, mass spectrometry, HPLC
      patterns, behavior to enzymatic treatments, and breaking of purine ring after
      acid treatment. Nevertheless, their biological activities are about two orders of
      magnitude higher than those of commercially available inosine and hypoxanthine
      standards. Biological activities became practically identical when these were
      processed (HPLC) in the same way as native molecules. A study to explain such a
      discrepancy is in progress.

PMID- 7625879
TI  - Hormone profiles and testicular histology in azoospermic men with Y-autosome
      translocation and autosomal translocation.
AB  - Hormone profiles and testicular histology were studied in azoospermic men with Y
      autosome translocation and autosomal translocation. Plasma levels of LH, FSH,
      prolactin, and testosterone were within normal ranges in these anomalies. The
      responses of plasma gonadotropins to LH-RH and plasma testosterone to hCG were
      similar in the two groups. Johnsen score count, diameter of the seminiferous
      tubules, wall thickness, and Leydig cells per seminiferous tubules were similar
      in the two groups. It would appear that hormone conditions an alterations are
      similar in azoospermic men with Y-autosome translocation and autosomal
      translocation.

PMID- 7625880
TI  - Hypoosmotic swelling test for quality control of sperm prepared for assisted
      reproduction.
AB  - This study evaluates the clinical usefulness of one additional parameter for
      assessment of human sperm cell function in vitro--the hypoosmotic swelling test.
      The hypoosmotic swelling test evaluated the functional integrity of the sperm
      plasma membrane. The investigation included a comparison of the hypoosmotic
      swelling test in samples containing motile and immotile spermatozoa and their
      correlation with the intrauterine insemination outcome. Motile spermatozoa
      expressed better membrane characteristics, without any importance of the
      hypoosmotic conditions. Positive correlation exists between HOS results and the
      outcome of IUI. This test can be a useful addition to the standard battery of
      semen analyzing tests.

PMID- 7625881
TI  - Effect of nizofenone on experimental head trauma in mice.
AB  - The therapeutic effect of nizofenone, a cerebroprotective drug, on experimental
      traumatic head injury was investigated in mice. The animals under halothane
      anaesthesia were subjected to a severe concussive head trauma and their
      neurological status was assessed by a string grip-test for 6 consecutive days.
      The neurological function of the control groups fell markedly 1 hr after trauma
      and slowly recovered day by day, but some animals failed to restore to the normal
      level, even on the 6th day. The post-treatment of the head-injured mice with
      nizofenone (3 mg/kg/day, i.p.) significantly improved the neurological function.
      The neurological improvement by nizofenone was dose-dependent and a significant
      amelioration was observed at 0.3 mg/kg/day. Methylprednisolone (30 mg/kg/day,
      i.v.) did not exert any significant neurological improvement in this therapeutic,
      experimental condition. In this study, nizofenone treatment was found to
      beneficially influence the recovery of the neurological function, maybe by
      reducing the progress of brain injury following head trauma.

PMID- 7625883
TI  - Effects of nifedipine and TMB-8 on angiotensin II-induced mesenteric
      vasoconstriction in dogs.
AB  - The effects of a Ca2+ entry blocker, nifedipine, and a putative intracellular
      Ca2+ release inhibitor, 8-(N, N-diethylamino) octyl-3,4,5-trimethoxybenzoate (TMB
      8), on mesenteric vasoconstriction, induced by angiotensin II, were examined in
      anesthetized dogs. Injection of angiotensin II (5 and 10 ng/kg) into the
      mesenteric artery decreased the mesenteric blood flow, which was suppressed
      during intramesenteric arterial infusion of TMB-8 (30 and 100 micrograms/kg/min)
      but not of nifedipine (0.03 and 0.1 microgram/kg/min). A higher dose of
      nifedipine (0.3 microgram/kg/min) only slightly attenuated the mesenteric blood
      flow response. Intravenous injection of angiotensin II (100 ng/kg) decreased the
      mesenteric and renal blood flow. Both blood flow responses were suppressed during
      intravenous infusion of TMB-8 (1 and 2 mg/kg/min). Intravenous infusion of
      nifedipine (0.1-1.0 microgram/kg/min) suppressed the renal blood flow response,
      whereas the mesenteric blood flow response was relatively resistant to
      nifedipine. The present results suggest that a TMB-8-sensitive Ca2+ movement
      pathway participates in the angiotensin II-induced contraction of the dog
      mesenteric vasculature in vivo. The Ca2+ influx through dihydropyridine-sensitive
      Ca2+ channels may not play a significant role in the angiotensin II-induced
      mesenteric vasoconstriction.

PMID- 7625882
TI  - Effects of chronic caffeine on adenosine, dopamine and acetylcholine systems in
      mice.
AB  - Chronic ingestion of caffeine by male NIH Swiss strain mice leads in about 3 days
      to a significant increase in A1-adenosine, nicotinic and muscarinic receptors,
      and a significant decrease of beta 1-adrenoceptors in cerebral cortical
      membranes. Plasma levels of caffeine in the chronically treated mice range from
      0.70 to 5.7 micrograms/ml. The changes in receptors reverse after withdrawal of
      caffeine within 7 days. An increase in nitrendipine binding sites, associated
      with L-type calcium channels, also occurs within 4 days and has reversed in 7
      days after withdrawal. There is no change in the levels of striatal nicotinic
      receptors of D2-dopamine receptors, nor of [3H]cocaine binding to dopamine uptake
      sites. Levels of opioid receptors are either increased (delta) or unaltered (mu,
      kappa). sigma-Receptors are unaltered. Stimulations of striatal adenylate cyclase
      by forskolin, dopamine and NECA are not significantly affected after chronic
      caffeine ingestion. The adenosine agonist, NECA, reverses the amphetamine
      elicited increases in locomotor activity and partly reverses the cocaine-elicited
      increases. The NECA dose-response curve is multiphasic (depression, stimulation
      and then depression) versus amphetamine in control mice, but only depressant
      versus amphetamine in chronic caffeine mice, while being multiphasic versus
      cocaine in both control and chronic caffeine mice. NECA reverses the stimulation
      of locomotor activity elicited by the muscarinic antagonist, scopolamine, and is
      more effective in the chronic caffeine mice. The behavioral depressant effects of
      the muscarinic agonist, oxotremorine, are not markedly altered after chronic
      caffeine ingestion.

PMID- 7625884
TI  - Comparative vasodepressor effects of 3-pyridine derivatives possessing the
      cyanoamidine or amide structure in pithed rats.
AB  - The potency and mechanism of the vasodepressor action of N-cyano-3
      pyridinecarboximidamide and nicotinamide, which are 3-pyridine derivatives
      possessing cyanoamidine and amide structures, respectively, were studied in
      pithed rats infused with phenylephrine. The N-substituents of cyanoamidine and
      amide in the derivatives studied comprised 2-nitroxyethyl (KRN2391 and
      nicorandil), phenethyl (Ki769 and Ki765) and 2-(2-chlorophenyl)ethyl (Ki3005 and
      Ki4261) moieties. These derivatives produced vasodepressor actions in a dose
      dependent manner, except for Ki4261 which did not show any action below the
      solubility limit. When the vasodepressor effects of compounds possessing the same
      N-substituents in cyanoamidine and amide derivatives were compared, the potency
      of cyanoamidine derivatives was greater than that of amide derivatives, Ki3005
      being the most potent. The vasodepressor effects of cyanoamidine and amide
      derivatives were antagonized by glibenclamide, although the antagonism of the
      depressor effects of KRN2391 and nicorandil was less pronounced than that of the
      other derivatives. These results suggest that N-substituents, in addition to the
      cyanoamidine structure, play an important role in determining the vasodepressor
      potencies of 3-pyridine derivatives. Furthermore, the vasodepressor effects of
      these derivatives appear to be based on their K+ channel-opening actions,
      although those of KRN2391 and nicorandil seem to be partly mediated by a nitrate
      like action in addition to their K+ channel-opening action.

PMID- 7625885
TI  - Analysis of 16,16-dimethylprostaglandin E2-induced diarrhea in cecectomized rats.
AB  - The 16,16-dimethylprostaglandin E2 (dmPGE2)-induced diarrhea was analyzed in
      cecectomized rats prepared by resecting the cecum and its vasculature without
      disturbing the ileocecal junction. dmPGE2 (0.1-1.0 mg/kg, p.o.) dose-dependently
      increased the number of defecation episodes and induced a soft and watery stool
      in cecectomized rats. At 0.3 mg/kg, the diarrhea-inducing effects of dmPGE2 were
      more pronounced in cecectomized than in control rats. When given i.p., dmPGE2
      (0.3 mg/kg) induced a watery stool in cecectomized and control rats with the same
      efficacy, although these effects were short-lasting as compared to oral
      administration. Castor oil (4 ml/kg, p.o.) also induced diarrhea, but did not
      produce a watery stool in cecectomized rats. There were no differences between
      cecectomized and control rats in basal small intestinal transits or in dmPGE2
      (0.3 mg/kg, p.o.)-induced enhancements. Moreover, the basal and dmPGE2-induced
      jejunal net fluid transfers were the same in cecectomized and in control rats. On
      the other hand, the enhanced secretion of colonic fluid by dmPGE2, given
      intraluminally, was only half of that in control rats, whereas the colonic
      transit-enhancing effect of dmPGE2 in cecectomized rats was more pronounced than
      in control rats at 15 but not at 30 min after its administration. The basal
      colonic fluid contents and transits were the same in cecectomized and in control
      rats. Loperamide and morphine (0.1 and 1.0 mg/kg, s.c.) inhibited the dmPGE2 (0.3
      mg/kg, p.o.)-induced diarrhea in cecectomized rats. N-methyllevallorphan (5
      mg/kg, s.c.) completely antagonized the inhibitory effect of loperamide and
      partly antagonized the effect of morphine. These results suggest that oral
      administration of dmPGE2 induces a more pronounced secretory diarrhea in
      cecectomized than in control rats, probably due to the lack of the reservoir
      function of the cecum in the operated animals. This secretory diarrhea model is
      suitable for evaluating the antidiarrheal activity of drugs.

PMID- 7625887
TI  - Transitory effects of intracerebral administration of protein synthesis
      inhibitors on rat's spontaneous behavior.
AB  - In order to evaluate whether the effects of the local administration of protein
      synthesis inhibitors are transient or permanent, small volumes of cycloheximide,
      2-deoxy-d-galactose, tetrodotoxin, and saline solution were stereotaxically
      administered in the amygdala, substantia nigra, and nucleus basalis
      magnocellularis of naive male adult Wistar rats. Three spontaneous activities
      (feeding, drinking, locomotion) were continuously recorded. 12 groups of animals
      were housed in activity cages for 6 consecutive days with a light/dark schedule
      (LD 12:12). The active compounds at doses sufficient to cause only limited
      effects were administered at the beginning of the light period of the fourth day.
      During the initial three days spontaneous activities remained constant, following
      the normal circadian distribution of rodents. Cycloheximide and tetrodotoxin
      administrations were followed by transient site-specific and activity-specific
      changes, which occurred only during the fourth and fifth day. The results show
      that protein synthesis inhibitors can be locally administered into the CNS at
      doses affecting only limited subcortical structures. The observed modifications
      of the three spontaneous activities were all transient and were always followed
      by complete recovery within 48 hours, thus confirming previous biochemical data.
      Therefore, the local injection of protein synthesis inhibitors, like
      tetrodotoxin, lidocaine or other compounds, can be employed to induce transient
      functional effects on well delimited brain structures in order to study the time
      course of the mechanism of mnemonic trace formation.

PMID- 7625886
TI  - Effect of Y-25130, a selective 5-hydroxytryptamine3 receptor antagonist, on
      gastric emptying in mice.
AB  - The effect of Y-25130 on gastric emptying of nutrient test meals (solid chow) was
      examined in mice. In a dose range of 0.01-1 mg/kg, p.o., Y-25130 significantly
      accelerated gastric emptying of solid meals in a dose-dependent manner, at an
      ED30 of 0.021 mg/kg. Other 5-hydroxytryptamine3 receptor antagonists and
      prokinetic agents having 5-hydroxytryptamine3 receptor antagonistic properties
      accelerated the emptying of solid meals in the following rank order of potency: Y
      25130 = granisetron > or = tropisetron > ondansetron > cisapride >
      metoclopramide. The acceleration of the gastric emptying showed a good
      correlation with the antagonistic potencies of these compounds on 5
      hydroxytryptamine3 receptors, determined by the inhibition test of the von Bezold
      Jarisch reflex in anesthetized rats (r2 = 0.99). Domperidone (1 and 10 mg/kg,
      p.o.) and trimebutine (10 and 100 mg/kg, p.o.) failed to increase the rate of
      emptying from the stomach. Cisplatin (30 mg/kg, i.p.), a chemotherapeutic agent,
      significantly delayed the gastric emptying of solid meals, and Y-25130 (0.1-1
      mg/kg, p.o.) prevented such a delay in emptying in a dose-dependent manner. These
      results suggest that Y-25130 accelerates the gastric emptying in mice by
      antagonism of the 5-hydroxytryptamine3 receptor.

PMID- 7625888
TI  - Elevated levels of nerve growth factor in the thalamus and spinal cord of rats
      affected by experimental allergic encephalomyelitis.
AB  - In a previous study it was shown that the levels of NGF in the cerebrospinal
      fluid of patients affected by multiple sclerosis (MS) increase during the acute
      phase of the disease and decrease in the remission phase. In the present study,
      using an animal model of MS, we investigate whether any changes in NGF levels
      occur in brains of rats affected by Experimental Allergic Encephalomyelitis
      (EAE). The results show an enhanced level of NGF in the thalamus and spinal cord
      and a numerical increase of mast cells (MCs) expressing mRNA-NGF localized in
      these two regions. These observations suggest that NGF is involved in EAE and
      that MCs contribute to the local increase of NGF.

PMID- 7625889
TI  - Fos-positive cells associated with forced wakefulness in the hypothalamus of the
      rat are not GABAergic.

PMID- 7625890
TI  - The relationship between fusion index and stimulation frequency in tetani of
      motor units in rat medial gastrocnemius.
AB  - The relationship between tetanic fusion and frequency of stimulation was
      investigated in 81 motor units of the rat medial gastrocnemius. A fusion index
      was calculated for tetani evoked by trains with constant frequency stimuli. This
      index is expressed as the ratio of a/b, where a is the distance from a baseline
      to the maximal relaxation before the last component of tetanus and b is the peak
      amplitude of the last component. The fusion-frequency relation has a sigmoid
      shape. The steep portion of the relation corresponds to lower frequencies for
      slow motor units than for fast units. Among the fast units, FR motor units are
      fused at somewhat lower frequencies than FF ones. However, the increase in fusion
      index per 1 Hz change in frequency of stimulation for the three types of motor
      units is similar. This observation suggests a similar course of fusion within
      different motor units. The fusion index shows a correlation with the contraction
      time as well as with the half-relaxation time.

PMID- 7625891
TI  - A morphological and morphometrical study of displaced amacrine cells in dog
      retina.
AB  - The morphology and morphometry of displaced amacrine cells (DACs) have been
      investigated in dog retina with the aim of finding out differences in relation to
      their distance from the optic papilla and to their location within the nasal and
      temporal retina. The study was performed by using the Boycott and Peichl's silver
      impregnation method in wholemount retina (12) while the morphometry of the cell
      body and of the dendritic field was carried out by Leitz ASM 68K image analyser.
      No morphological difference was found between nasal and temporal cells although a
      variability, sometimes significative, in their morphometry was observed.
      Moreover, the morphological features of the DACs remained constant even by
      varying their distance from the optic papilla.

PMID- 7625892
TI  - Individual differences in slow brain potentials in a guessing task.
AB  - 18 healthy right-handed subjects had to predict one of two random non
      equiprobable events by pressing one of two buttons with the right index finger.
      Each trial was preceded by a cue that increased the probability of the
      corresponding event in comparison to its overall probability. The
      Bereitschaftspotential (BP) before an action and the stimulus-preceding
      negativity (SPN) between the action and the event presentation were recorded. The
      subjects were subdivided into groups according to their tendency to follow the
      cue or to reject it. Cue rejection provided in the present situation a larger
      final gain than cue acceptance. Those subjects who used the former strategy were
      characterized by a local BP increase over the right parietal cortex, when a low
      probable cue was presented. Their SPN amplitude was relatively small, but it
      increased substantially after a low-probable cue. Subjects who tended to follow
      the cue had a very large BP amplitude over the projection area and at vertex.
      Their SPN was overall large, regardless of condition. Peculiarities of the
      potentials recorded in these subjects are thought to relate to their desire to
      minimize errors.

PMID- 7625893
TI  - An overview of managed health care.

PMID- 7625894
TI  - America's health care system.

PMID- 7625895
TI  - The College of American Pathologists Conference XXVII on the Impact of Managed
      Care on the Practice of Pathology, November 4, 1994.

PMID- 7625896
TI  - A pathologist is as a pathologist does. Changing roles in a changing time.
AB  - Managed care challenges pathologists to a paradoxical cultural transition
      requiring clinical participation in the community while refining competitive
      managerial skills to maintain a livelihood. This presentation explores several
      role changes that a pathologist may undertake to acquire perceived clinical and
      economic value in a managed care system.

PMID- 7625897
TI  - Managing opportunities under managed care.
AB  - Health care reform is driving significant changes in associations between
      physicians, hospitals, insurers, and patients. This restructuring of the delivery
      of care will affect the practice of pathology. At these crossroads, practices
      have to decide to continue without change or to adopt new approaches. Horizontal
      mergers between pathology practices offer one opportunity under health care
      reform. Such mergers reflect the general trend toward consolidation of operations
      as a cost-effective approach to health care delivery. They will require a
      reevaluation of the manpower needs in pathology. The move to consolidated health
      plans also suggests that pathology practices should consider vertical integration
      with other physicians. Restructuring of practices is not the sole answer to
      addressing health care reform. Practices must become involved in cost-saving
      strategies in the systems.

PMID- 7625898
TI  - Academic medical centers and managed care.
AB  - Academic medical centers are threatened by the expansion of managed care.
      Hampered by their higher cost, lack of primary care capability and specialist
      orientation, organizational sluggishness and inflexibility, and relative lack of
      managerial expertise, these organizations, long a national resource in education,
      research, and clinical care, face an uncertain future. Academic pathology
      departments must aggressively manage their resources and maximize their market
      advantages to compete effectively.

PMID- 7625900
TI  - College of American Pathologists Conference XXVII on the Impact of Managed Care
      on the Practice of Pathology: keynote address.

PMID- 7625899
TI  - Commentary on the future of pathology practice in the United States.
AB  - The rapidly changing climate of health care delivery threatens the traditional
      control pathologists have had over their profession. However, new opportunities
      have been created. The strength of articles such as those by Sodeman and Elevitch
      is found not only in their content, but also in the impetus they provide for
      continuing the forum for discussion of change of the profession's future role in
      our health care system.

PMID- 7625901
TI  - There is no such thing as 'strategic' planning. A primer for pathologists.

PMID- 7625902
TI  - Practicing pathology as a health care contractor. Business planning for managed
      care.
AB  - Managed care requires a pathology practice to take on the role of a health care
      contractor whose existence depends on obtaining, managing, and renewing
      competitively bid contracts for the group's services. This presentation is a
      primer on how to write a formal business plan for a pathology practice using a
      model case study to illustrate, among several business issues, the differences
      between and the key elements for success in operating a pathology practice in
      both fee-for-service and capitated managed care environments.

PMID- 7625903
TI  - The pathologist and managed care. Integration into the new health care delivery
      system.
AB  - As the health care system evolves, managed care plans are expanding rapidly, and
      pathologists face radical changes in contractual relationships and payment
      methodology. As a result, entirely new relationships will often need to be
      negotiated to adapt successfully. The experience of pathologists in areas where
      there is already high market penetration by managed care plans can be used in
      strategic planning, learning to gain entry to negotiations, and planning what and
      how to negotiate. Proper preparation is critical to successful negotiations in
      our new health care system and requires an understanding of capitation,
      contracting risks, and opportunities.

PMID- 7625904
TI  - Integrating yourself into the new health care delivery system. A Florida
      experience.

PMID- 7625905
TI  - A market analysis approach to bidding for capitated clinical laboratory and
      pathology services contracts.
AB  - Traditional episodic, fee-for-service medical care and indemnity-type insurance
      are rapidly being replaced by managed health care plans that often include
      financial risk assumption by health care providers. This paper describes the
      application of marketing principles to the evaluation and capture of capitated
      clinical laboratory and pathology services contracts. It includes a method for
      developing capitation rates and describes advantages enjoyed by hospital-based
      laboratories that enhance their competitiveness in the marketplace.

PMID- 7625906
TI  - Pathology group management. Dealing with growth.

PMID- 7625907
TI  - The hospital-based group in a managed care environment. Reading the terrain.
AB  - The root-level changes in health care delivery that are in progress will make
      demands on pathologists that are almost without precedent in the post-Medicare
      era. Their turbulent pace and uncertain direction confer an added sense of
      urgency to the need for an effective response. For pathologists, the most
      uncomfortable changes may involve assuming responsibilities that are a marked
      departure from traditional training and practice. Chief among these are a need
      for more familiarity with the ways a corporate structure operates, a more
      thorough understanding of the needs and wants of buyers of physicians' services,
      and the ability to manage a practice successfully as an enterprise. Despite the
      variety of current approaches to managed care, there are common themes that
      invite the careful consideration of pathologists. Many of these reflect basic
      problems with which care managers must cope routinely. Of equal importance to the
      future success of pathology practice is the need to develop a high level of skill
      in constantly evaluating the strengths, weaknesses, and future directions of
      one's own practice.

PMID- 7625908
TI  - Kaiser Permanente. An insider's view of the practice of pathology in an HMO
      hospital-based multispecialty group.
AB  - The practice of pathology in a physician-driven health maintenance organization
      can be professionally and personally satisfying. Much of what The Permanente
      Medical Group has learned is applicable, comforting, and helpful to other
      pathologists. The organization of Kaiser Permanente, the largest health
      maintenance organization in the United States, is presented, as are some of the
      pertinent practice parameters of its pathologists.

PMID- 7625909
TI  - Practicing pathology through multiple hospitals at multiple sites. Practice
      management issues.
AB  - OBJECTIVE: To describe a successful method of management for pathologists to use
      in an environment of hospital consolidation and managed care. DESIGN: This
      article draws on the experience of a large, pathologist-owned regional laboratory
      in applying management principles needed for practice in the future. SETTING: A
      group of 20 pathologists, with 19 affiliated pathologists (multiple groups)
      practicing in rural and urban areas of five states in the Southern Plains.
      PRINCIPAL FINDINGS: Planning, personnel management, organizational structure,
      finance, and information systems are necessary keys for pathology management in a
      dispersed system. CONCLUSION: The opportunity exists for a professionally and
      economically satisfying practice in the medical environment of the future.

PMID- 7625910
TI  - The practice of pathology in the next decade. Consolidation and networking
      leading to the community laboratory.

PMID- 7625911
TI  - Marketing the pathology practice.
AB  - Effective marketing of the pathology practice is essential in the face of an
      increasingly competitive market. Successful marketing begins with a market-driven
      planning process. As opposed to the traditional planning process used in health
      care organizations, a market-driven approach is externally driven. Implementing a
      market-driven plan also requires recognition of the definition of the service.
      Each market to which pathologists direct their service defines the service
      differently. Recognition of these different service definitions and creation of a
      product to meet these needs could lead to competitive advantages in the
      marketplace.

PMID- 7625912
TI  - The College of American Pathologists Conference XXVII on the Impact of Managed
      Care on the Practice of Pathology: summary.

PMID- 7625913
TI  - Festschrift to Dr. Horst Klinkmann, in celebration of his 60th birthday.

PMID- 7625914
TI  - A chronicle of excellence.

PMID- 7625915
TI  - Is the choice of membrane important for patients with acute renal failure
      requiring hemodialysis?
AB  - It has recently been reported that patients with acute renal failure requiring
      hemodialysis have an improved recovery of renal function and a higher survival
      rate when the dialysis treatments are performed with a biocompatible membrane
      rather than a bioincompatible membrane. Our data, obtained in 57 patients with
      acute renal failure, do not support these findings since neither the mortality
      nor the required number of dialysis sessions could be influenced by using a
      biocompatible membrane. The survival rate was similar in both groups (64 versus
      72%), and renal function was regained in both groups after 6 dialysis sessions.
      We conclude that when reviewing the literature as well as other factors, the
      underlying clinical condition or the skill of the physicians is probably more
      important than the theoretical superiority of biocompatible membranes.

PMID- 7625916
TI  - Biocompatibility in hemodialysis: clinical relevance in 1995.
AB  - Hemodialysis therapy for end-stage renal disease is still empirical even after
      more than 30 years of experience. Although long-term survival can now be assured
      in selected patients, clinical results tend to be disappointing. Hemodialysis
      therapy needs to be improved. Zealots of the biocompatibility school believe that
      this improvement will come from reducing undesirable consequences of blood
      membrane interaction, particularly complement activation. However, there is
      controversy over the clinical meaningfulness of biocompatibility when exclusively
      related to blood membrane interactions. Another dimension needs to be added,
      namely ultrapure dialysate to avoid subclinical chronic effects of activation of
      the cytokine cascade by bacterial fragments present in dialysate. While the
      pathogenesis of acute anaphylactoid reactions are understood and largely
      preventable, the relation of the chronic syndromes such as amyloidosis to the use
      of a particular membrane remain unproven. Prospective studies that will occupy at
      least a decade will be necessary to decide these issues.

PMID- 7625918
TI  - Hemodiafiltration in two chambers without replacement fluid: a clinical study.
AB  - Paired filtration dialysis (PFD) is the only hemodiafiltration (HDF) technique in
      which ultrafiltrate (Uf) is obtained continuously with a similar composition to
      plasma. It has been proved that Uf is regenerated when it passes through an
      uncoated adsorbent charcoal cartridge: this one removes medium-to-large solutes
      and small toxines (except for urea and phosphates), but not the electrolytes and
      bicarbonate. This regenerated Uf can be used like replacement fluid, using the
      same Uf pump as the infusion pump; this makes the HDF technique easier and more
      reliable. During 12 months (3 h/3 sessions/week), we treated 13 patients with
      this PFD-Charcoal technique. These patients were previously on conventional PFD
      for at least 6 months. The biochemical results were excellent with a
      stabilization of all parameters (urea, creatinine, uric acid, Na, K, Cl, Ca,
      phosphates, beta 2-microglobulin, beta 2M, etc.) and a better control of acidosis
      (statistically significative after 6 months). The clinical tolerance was also
      excellent, and the technique was greatly simplified. We conclude that PFD
      Charcoal is a good HDF technique that avoids the use of exogenous replacement
      fluid by using the regenerated Uf itself as an endogenous substitution fluid with
      bicarbonate.

PMID- 7625917
TI  - Considerations on developmental aspects of biocompatible dialysis membranes.
AB  - Modern strategies in developing new polymers for dialysis membranes aim to
      improve their blood compatibility. To achieve such a goal, two approaches have
      been successfully applied: existing cellulosic polymers were modified, either by
      introducing functional groups through ester or ether bonds, by mixing synthetic
      polymers with bulk additives, or by using copolymerization techniques. As a
      detailed example, the first synthetically modified cellulose membrane, Hemophan,
      was prepared by substituting some hydrogen atoms in the cellulosic glucose unit
      by diethyl-amino-ethyl groups with the modification having a considerable impact
      on the membrane's hemocompatibility. It is further known that the
      hemocompatibility of hydrophobic synthetic membranes is improved by rendering
      these materials partially hydrophilic. We tested the hypothesis, whether the
      hemocompatibility of a material, which is hydrophilic per se, such as unmodified
      cellulose, is changed after the introduction of hydrophobic substituents. For
      this purpose, the number and nature of substituents have been systematically
      varied in order to alter surface properties, and these variations have been
      subsequently related to blood compatibility parameters. As expected, thrombin
      generation as well as complement- and cell-activation depend on the number and
      nature of the substituents whereby some of the substituents show a very narrow
      optimum if their hemocompatibility is related to the degree of substitution.
      Changes in hemocompatibility can be followed by physical methods, such as surface
      angle analyses and zeta potential determinations. Data show that alterations in
      the lipophilic/hydrophilic balance on the polymer surface may explain substituent
      related changes in polymer hemocompatibility.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7625919
TI  - Protein adsorption by artificial membrane materials under filtration conditions.
AB  - Elevated plasma levels of numerous low molecular weight proteins (LMWP) in renal
      insufficiency are likely to contribute to the uremic syndrome. Dialysis-related
      amyloidosis, caused by the accumulation of beta 2-microglobulin (beta 2M), has
      highlighted the need for a renal replacement therapy that allows the elimination
      of LMWP in addition to small solutes. Synthetic membrane materials employed under
      hemofiltration conditions proved to be most effective in lowering elevated beta
      2M plasma levels. In addition to convection, protein adsorption to artificial
      membrane materials is an important mechanism for beta 2M removal. Using an in
      vitro setup, 12 commercially available hemofilters representing 11 different
      membrane materials were perfused with human blood containing 125I-labeled plasma
      proteins. Under filtration conditions, total protein adsorption ranged from 338
      2,098 mg/m2 of membrane surface, and the fraction of adsorbed LMWP varied between
      14-70% of total protein adsorption and was negatively correlated to total protein
      adsorption. beta 2M adsorption showed up to an 8-fold difference between
      membranes, and was negatively correlated with total protein adsorption and
      positively correlated with the adsorption of LMWPs.

PMID- 7625920
TI  - Influence of hydration state on plasma volume changes during ultrafiltration.
AB  - To assess the influence of hydration state on plasma volume (PV) changes during
      ultrafiltration, 11 clinically normhydrated patients on maintenance hemodialysis
      were studied intraindividually during 2 hydration states differing by 2-15% of
      lean body mass (LBM). Plasma volume was measured continually during a 15-min
      ultrafiltration test including an ultrafiltration of 1% of target weight and
      during a 45-min follow-up period of blood recirculation through the dialyzer
      without ultrafiltration. In all patients a maximal decrease in relative PV was
      more pronounced when there was less hydration and when the grade of hydration
      correlated inversely with the maximal response of PV decrease (r = -0.68, p <
      0.001). The same was observed between the hydration state and the slope of the PV
      decrease (r = -0.69, p < 0.001). Plasma refilling was estimated in the period
      following ultrafiltration. The slope of the plasma volume increase correlated
      with the grade of hydration (r = 0.31, p < 0.05) as did the asymtote of PV (r =
      0.4, p < 0.01). It is concluded that the less hydrated a dialysis patient is, the
      more pronounced will be the fall of the ultrafiltration-induced plasma volume and
      the less distinct will be the recovery of the plasma volume after the
      discontinuation of ultrafiltration.

PMID- 7625921
TI  - Theoretical description of mass transport in medical membrane devices.
AB  - The application of the one-dimensional theory of mass transport to the derivation
      of mathematical formulas for clearances of a variety of membrane mass exchangers,
      namely hemodialyzers, hemofilters, plasma separators, and the cascade filtration
      procedure, has been reviewed. The applied theory predicts that clearances depend
      approximately on fluid inlet flow rates but not on concentrations, and with
      constant fluid flow rates, clearances are constant. Also, the application of
      device clearance in kinetic modeling has been discussed.

PMID- 7625922
TI  - Function of endocrine organs in hemodialyzed patients of long-term erythropoietin
      therapy.
AB  - Endocrine abnormalities in patients with chronic renal failure are well
      documented. The present study aimed to assess the influence of long-term
      erythropoietin (EPO) therapy on endocrine abnormalities in hemodialyzed patients.
      Two groups of hemodialyzed patients, each of which comprised 17 subjects, were
      examined. The first group was treated by EPO (EPO group) while the second one did
      not receive this hormone (No-EPO group). A complete biochemical and hormonal
      check-up was performed before and at the 3, 6, 9, and 12 month points of the
      study period. Normal values for the estimated parameters were obtained in
      appropriately selected sex- and age-matched healthy subjects. After EPO therapy,
      an increase of the hematocrit value from 21.8 +/- 0.9 to 32.6 +/- 0.9% was
      observed, which was accompanied by a significant decline of plasma ferritin and
      saturation of transferrin. In patients of the No-EPO group, a significant
      although less marked rise of the hematocrit value (21.4 +/- 0.4 to 24.2 +/- 0.6%)
      was also noticed. EPO therapy did not change plasma levels of electrolytes (Na,
      K, Ca, inorganic phosphate), osteocalcin, creatinine, glucose, and alkaline
      phosphatase as well as plasma concentrations of calcium-related hormones (PTH,
      calcitonin, 1,25[OH]2D3), vasopressin, and triiodothyronine. EPO treatment
      induced a significant decrease in somatotropin, prolactin, follitropin, lutropin,
      ACTH, cortisol, plasma renin activity, aldosterone, noradrenaline, adrenaline,
      dopamine, glucagon, pancreatic polypeptide, and gastrin plasma levels and an
      increase in plasma insulin, estradiol, testosterone, atrial natriuretic peptide,
      thyrotropin, and thyroxine.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7625923
TI  - Lipid peroxidation and vitamin E in red blood cells and plasma in hemodialysis
      patients under rhEPO treatment.
AB  - Lipid peroxidation, measured by malonyldialdehyde (MDA) and vitamin E in red
      blood cells (RBC) and plasma, was investigated in 25 hemodialysis (HD) patients
      before and after 6 months rhEPO therapy. RBC-MDA was significantly elevated, but
      plasma MDA was in the reference range. After recombinant human erythropoietin
      (rhEPO) treatment, the MDA level was significantly decreased in both
      compartments. Marked vitamin E deficiency was established in RBC as well as in
      plasma. rhEPO therapy restored vitamin E levels in both compartments. Our data
      suggest a possible positive rhEPO-antioxidant effect in HD patients.

PMID- 7625924
TI  - Effects of lactate-based and bicarbonate-based peritoneal dialysis solutions on
      neutrophilic oxygen consumption.

PMID- 7625925
TI  - Selenium in uremia.
AB  - The importance of selenium as an essential trace element for man has been
      increasingly recognized during the last several years. Selenium deficiency has
      been associated with cases of congestive cardiomyopathy, skeletal myopathy,
      anemia, enhanced cancer risk, elevated incidence of cardiovascular disease,
      immune system alterations, hair and nail changes, and abnormalities in thyroid
      hormone metabolism. These symptoms are frequently present in chronic uremic
      patients. Nevertheless, the prevalence and significance of selenium deficiency in
      the uremic syndrome is still not clearly defined. This article reviews the
      selenium status in chronic uremic patients, the supposed pathogenetic mechanisms
      of selenium disturbance in uremia, and the possible role of selenium deficiency
      on some uremic abnormalities.

PMID- 7625927
TI  - "Intelligent" polymers in medicine and biotechnology.
AB  - One can define "intelligent" polymers as those polymers that respond with large
      property changes to small physical or chemical stimuli. These polymers may be in
      various forms, such as in solution, on surfaces, or as solids. One may also
      combine intelligent aqueous polymer systems with biomolecules to yield a large
      family of polymers that respond intelligently to physical, chemical, or
      biological stimuli. This article overviews such interesting and versatile polymer
      systems.

PMID- 7625926
TI  - Kinetic analysis of UDP-glucuronosyltransferase in bilirubin conjugation by
      encapsulated hepatocytes for transplantation into Gunn rats.
AB  - Kinetic analysis of the enzyme UDP-glucuronosyltransferase (UDPGT), responsible
      for the conjugation of bilirubin, suggests that it is a multisubunit enzyme in
      which there is cooperative binding of the substrate to the subunits. The binding
      of bilirubin to UDPGT shows positive cooperativity with an apparent Hill
      coefficient of 2.9. The binding of UDP-glucuronic acid (UDPGA) exhibits kinetics
      with mixed cooperativity with an apparent Hill coefficient of 4.028. Homogenized
      rat hepatocytes, intact hepatocytes, and hepatocytes encapsulated in alginate
      polylysine-alginate artificial cells, when incubated with bilirubin (1.6 mM) and
      UDPGA (20 mM), can form monoconjugated and diconjugated bilirubin. However, the
      presence of the artificial membrane offers some mass transfer resistance. The
      intraperitoneal transplantation into the Gunn rat of free and microencapsulated
      Wistar rat hepatocytes shows that both are equally effective in lowering the
      serum bilirubin. Thus, the membrane did not contribute to a lowering of efficacy
      after transplantation.

PMID- 7625928
TI  - Clinical trials of immunoadsorbent in systemic lupus erythematosus therapy.
AB  - Five patients with systemic lupus erythematosus (SLE) were perfused through an
      extracorporeal shunt filled with DNA-immunoadsorbent (DNA immobilized on
      carbonized resin beads). High concentrations of anti-DNA antibodies (36.4-67.0%)
      (binding percentage with 125I-DNA) in the serum of SLE patients were reduced to
      13.8-53.0%, respectively. The highest removal percentage was 62.1%. Although the
      decline levels varied, the symptoms of patients, i.e., long-term severe joint
      pain, severe edema, hydropericardium, and ascites were all relieved considerably.
      The immunoadsorbent showed satisfactory blood compatibility.

PMID- 7625929
TI  - Extracorporeal circulation with autogenous oxygenation: hemodynamic and
      gasometric parameters.
AB  - Ten experimental perfusions with autogenous oxygenation were performed in mongrel
      dogs to evaluate the efficacy of the procedure in maintaining normal hemodynamic
      the efficacy of the procedure in maintaining normal hemodynamic conditions and
      adequate blood gases for 1 h. Blood was drained from the right and left atria and
      pumped to the pulmonary artery and aorta, respectively. Two closed circuits
      containing compliant chambers and roller pumps were utilized. Artificial
      ventilation with an FiO2 of 50% were used in 5 animals and with an FiO2 level of
      30% in the other 5. EKG, cardiac output, aortic, pulmonary artery, and left
      atrium pressures were registered. Pulmonary tissue was biopsied after perfusion.
      The heart was electrically fibrillated after perfusion was established and
      defibrillated at the end of the bypass. The procedure was able to maintain blood
      gases and pulmonary, aortic, and left atrial pressures within normal ranges
      during the perfusion. The mobility of the heart and the access to all coronary
      arteries was excellent. Clinical central nervous system evaluation, EKG tracings,
      and pulmonary histological exams showed no adverse effects of perfusion. We
      conclude that the technique employed may present a suitable proceeding for
      extracorporeal circulation in closed heart surgeries, and its clinical
      application should be evaluated as a safe and economical alternative.

PMID- 7625930
TI  - From wooden limbs to biomaterial organs: the ethics of organ replacement and
      artificial organs.
AB  - This paper discussed issues of ethical assessment and moral concern associated
      with organ replacement and physical enhancement: research, allocation, organ
      donation, artificial organs, xenografts, biomaterials, and neuromaterials. While
      emphasizing the medical and moral benefits over associated risks, it calls for a
      better integration of moral assessment into technology assessment and for the
      establishment of a cross-cultural and interdisciplinary International Ethics
      Committee for Organ Replacement Therapy.

PMID- 7625931
TI  - Facing the reality: the world cannot afford uremia therapy at the start of the
      21st century.
AB  - Although remarkably successful in prolonging useful life, there is minimal
      probability that the majority of the world's population will benefit from
      contemporary therapy for irreversible renal failure because of its inordinately
      high cost in light of available resources. While affluent nations establish
      priorities for allocation of slots for maintenance dialysis of recipients of
      organ transplants, poor and developing countries must await the development of
      inexpensive, low technology treatments to substitute for absent kidney function.
      One attractive potential alternative to contemporary uremia therapy is the use of
      the intestine as a giant substitute and somewhat displaced nephron. Possible
      means of extracting wastes via the gut include ingestion of a mixed oral sorbent,
      instillation of bacterial crystallized enzymes to transform nitrogenous wastes to
      essential amino acids, or administration of high osmolality laxatives to promote
      diarrhea containing nitrogenous wastes. Any of these approaches may extract
      sufficient solute and water to sustain anephric life. An optimistic view of
      evolving uremia therapy is that within the next decade pills and purges for the
      poor may supplant more effective though expensive high technology approaches now
      encompassed in so-called modern nephrology.

PMID- 7625932
TI  - Management of ocular burns.
AB  - This article aims to provide a practical, safe and effective approach to the
      management of ocular burns of any cause. This approach is based on an
      understanding of the effects of burn injury on ocular tissues and the principles
      of promoting a return to normal health and function. Some specific management
      protocols are described and the complications of burns discussed.

PMID- 7625933
TI  - Diagnosis of double vision in adults.
AB  - Double vision is a distressing condition and needs immediate investigation.
      Diagnosis is simple and appropriate treatment should follow.

PMID- 7625934
TI  - Initial management and transport of patients with perforating eye injuries.
AB  - The first 24 hours are critical for a good surgical result from perforating eye
      injuries. The basic principles of initial management and transfer include
      prevention of vomiting, pain and infection, and avoidance of further injury.
      Where air transport is necessary it must be with the cabin altitude at sea level,
      or as low as is safe. Surgical repair should be undertaken as promptly as is
      practical.

PMID- 7625935
TI  - Amblyopia--or lazy eye.
AB  - An amblyopia, or lazy eye, is an eye that is healthy in all respects but which
      has defective vision, even after the fitting of correcting lenses for a
      refractive error. Amblyopia can be a strongly hereditary condition. The author
      describes the predisposing conditions and discusses methods of assessment and the
      effectiveness of its present treatment.

PMID- 7625936
TI  - General practitioners in hospitals.
AB  - The authors review General Practitioners in Hospitals, a report prepared by the
      School of Medical Education, University of New South Wales (1993) for the
      Australian Health Ministers' Advisory Council Medical Workforce Group on Hospital
      Training and Career Development. The authors acknowledge that this report
      represents the most comprehensive look at GP involvement in hospitals across
      Australia, but suggest that its conclusion 'general practitioners play a
      substantial role in the provision of medical care in public hospitals around
      Australia' may be an overstatement. They discuss shortcomings associated with the
      study, including: definitional issues; variation in levels of involvement
      according to hospital type; potential biases introduced by using self-report of
      hospital administrators as the source of data; insufficient emphasis being placed
      on the views of GPs; and the validity of extrapolations.

PMID- 7625937
TI  - Controlled drinking program in general practice.
AB  - Controlled drinking programs are feasible to run in general practice. They add
      another important dimension to health promotion activities. Adapting the program
      to the clinic's time and budget resources is the main challenge facing clinics
      wishing to set up such a program.

PMID- 7625938
TI  - Doctor shopping.
AB  - Many patients attending a drug and alcohol treatment service reported doctor
      shopping for benzodiazepines as "all too easy". How, we asked, could this
      activity be recognised and countered? This paper describes this activity and the
      attitude of some of the doctors affected by it.

PMID- 7625939
TI  - Type 2 diabetes. Patient practices, and satisfaction with GP care.
AB  - OBJECTIVE: To document patients' practices and management of DM2, their
      satisfaction with diabetes care and their quality of life and functional status.
      DESIGN: Anonymous questionnaire completed by 467 patients recruited by 204 GPs in
      124 practices in the Perth metropolitan area. RESULTS: Patients reported an
      adequate amount of monitoring for stable DM2. However, they lacked awareness of
      diabetes risk factors and complications from which they already suffered. Some
      90% of patients reported a high level of satisfaction with GP care and only 2.4%
      of patients had more than a moderate degree of functional disability. CONCLUSION:
      Patients have a high level of satisfaction about the diabetes care received from
      their general practitioner. However, they lack awareness of their risk factors
      and complications of diabetes. A simple strategy is proposed to improve these
      deficits and to share the responsibility for diabetes care between patient and
      doctor.

PMID- 7625940
TI  - Well child care records for use in Australian general practice.
AB  - According to WONCA, 'the discipline of general practice/family medicine needs to
      be firmly established as the central discipline of medicine around which medical
      and allied health disciplines are arranged to form a co-operative team for the
      benefit of the individual, the family and the community.' Well child care is an
      important part of general practice. By using the records presented in this paper
      at the time of both routine and opportunistic age specific visits, comprehensive
      well child care can be provided through the efficient teamwork of family doctors
      and practice nurses. Comments or suggestions for improving the records can be
      sent to Dr R Janes.

PMID- 7625941
TI  - Contrasts between metropolitan and rural general practice in the delivery of
      after-hours care.
AB  - OBJECTIVE: To describe: 1. current arrangements for the delivery of after-hours
      primary care in general practice. 2. GPs' satisfaction with these arrangements,
      and 3. the perceived barriers to improving after-hours care in general practice.
      DESIGN: Telephone survey of a random sample of general practitioners using a
      standardised questionnaire. SETTING: Two general practice populations, one urban
      (Central Sydney Division), and one rural (Central Western Division). RESULTS: The
      response rate was 71%. Almost all rural GPs (95%) provided after-hours care
      whereas 50% of urban practices provided after-hours care for their patients.
      Rural GPs expressed a significantly higher degree of satisfaction with their
      after-hours care arrangements. Half of the GPs providing all their after-hours
      care reported that they would be prepared to enter into co-operative arrangements
      with other practices. Thirty-seven per cent of urban GPs who did not provide all
      their after-hours care indicated that they would be prepared to enter into co
      operative arrangements with other practices. CONCLUSIONS: Many of the barriers to
      providing effective after-hours care may be overcome by establishing after-hours
      co-operatives.

PMID- 7625942
TI  - Update on sporotrichosis.
AB  - Sporotrichosis is endemic in temperate and tropical regions of the world,
      including Australia. Although uncommon, it is frequently encountered in Northern
      Australia, especially in Queensland. All ages are affected, although most cases
      occur from occupational exposure to vegetation or soil. This article reviews the
      cause, diagnosis and treatment options of this fungal disease which affects the
      skin and is often misdiagnosed. It classically presents in gardeners, especially
      those handling roses.

PMID- 7625943
TI  - Utilising patient feedback in the RACGP training program. An exploratory study.
AB  - The doctor-patient relationship is the hub of general practice. Today, there is
      an increasing use of patients in the evaluation of doctors' interpersonal skills.
      This paper reports on the findings of an exploratory study designed to
      investigate the feasibility of using patient feedback as an educational tool for
      GP trainees.

PMID- 7625944
TI  - HIV: patients attitudes to GPs.
AB  - OBJECTIVES: To describe the characteristics of HIV-infected patients attending
      hospital HIV outpatient clinics in Melbourne and to measure their attitudes to
      general practitioners. DESIGN: Data were collected by attending physician and by
      a self administered anonymous questionnaire given to patients sequentially and
      returned by prepaid envelope. SETTING: Tertiary hospital HIV outpatient clinics.
      PATIENTS: HIV-infected patients willing and able to participate. RESULTS:
      Response rate 61%. This sample had high occupational status and functional
      capacity, and 63% had had GP care before hospital attendance. Only a small number
      of GPs are involved, and their involvement declined after hospital care
      commenced. There was strong overall support for shared care, although only 7%
      supported predominant care by a GP in the terminal phase, and only 39% supported
      predominant care by a GP when completely well. The major factors determining
      attitude toward GPs were the GPs' attitude, confidentiality and service, with
      knowledge and skills being more important for GPs who have a special interest in
      HIV care. CONCLUSIONS: This group of patients have particular concerns about GPs
      that need to be addressed if GPs are to increase their involvement in HIV care.

PMID- 7625945
TI  - Information technology improving health care delivery in Arnhemland.
AB  - This paper will outline the modification of an existing medical records system
      called Health Planner to meet the needs of three health services servicing
      communities and outstations in Arnhemland. Improved continuity of care and
      program planning has resulted from computerisation.

PMID- 7625947
TI  - Management of angina.

PMID- 7625946
TI  - Practice tip. Non surgical treatment for meibomian cysts.

PMID- 7625948
TI  - Musculoskeletal medicine tip. Ischial bursitis.

PMID- 7625949
TI  - Patient education. Essential tremor.

PMID- 7625950
TI  - Acute skin eruption in a sick child.

PMID- 7625951
TI  - Thirty years on.

PMID- 7625952
TI  - Vocational training for rural practice.

PMID- 7625953
TI  - Burn management.

PMID- 7625954
TI  - Cold sores and shingles.

PMID- 7625955
TI  - Anaesthesia for children's lacerations.

PMID- 7625956
TI  - The early detection of primary open angle glaucoma. What is the GP's role?

PMID- 7625957
TI  - Eye problems in general practice. To refer or not to refer.
AB  - A significant number of eye problems present to the general practitioner. Most of
      these can be handled without referral to a specialist. This article attempts to
      give some guidance to the practitioner faced with an ophthalmological problem in
      the office. Sophisticated equipment is required in very few cases to make a
      working diagnosis. General practitioners should continue to be involved in
      primary eye care.

PMID- 7625958
TI  - Burns to the eye: an overview.
AB  - The assessment and management of eye burns and burns to the region of the eye may
      be complex. This article aims to provide an understanding of the basic principles
      of the reaction of ocular tissues to injury, the healing processes, the
      restoration of normal function and the causes of burns.

PMID- 7625959
TI  - Respiratory training prior to exposure in vivo in the treatment of panic disorder
      with agoraphobia: efficacy and predictors of outcome.
AB  - Thirty-two patients suffering from panic disorder with agoraphobia were treated
      with repeated hyperventilation provocations and respiratory training, followed by
      exposure in vivo. The treatment was evaluated with a comprehensive set of outcome
      measures, including self-report questionnaires, a multitask behavioural avoidance
      test and continuous monitoring of panic. The treatment was found effective for
      the majority of patients in diminishing the frequency of panic attacks and
      agoraphobic avoidance. The clinical relevance of the treatment effect was
      evidenced by the considerable number of patients that recovered. The effect of
      the treatment was sustained over a three and six month follow-up period. The
      prognostic value of a number of variables for treatment outcome was also
      investigated. Three variables accounted for the majority of the variance in
      treatment outcome: a higher pretreatment level of agoraphobic complaints, use of
      psychotropic medication and a longer duration of the disorder were associated
      with poorer outcome. Other variables, such as the therapeutic relationship and
      the quality of the marital bond, had no prognostic value.

PMID- 7625960
TI  - Gender differences in obsessive compulsive disorder.
AB  - We investigated gender differences in 219 patients with obsessive compulsive
      disorder consecutively referred to a centre specialising in the behavioural
      treatment of anxiety disorders. Females had a later mean onset-age, and were more
      likely to be married and to have children; they were also marginally more likely
      to have a past history of an eating disorder or depression, while males were more
      likely to have a history of anxious or meticulous personality traits. Family
      loading for psychiatric disorders did not differ significantly between the sexes.
      The results are discussed in the context of the epidemiological literature on
      gender differences in OCD.

PMID- 7625961
TI  - A comparison of two structured diagnostic interviews: CIDI and SCAN.
AB  - The relationship between and the inter-rater reliability of the Composite
      International Diagnostic Interview (CIDI) and the Schedules for Clinical
      Assessment in Neuropsychiatry (SCAN) for anxiety and depressive disorders were
      explored. The CIDI and the SCAN were administered by trained interviewers in
      counterbalanced order. A subsample of interviews was observed to determine the
      inter-rater reliability of the instruments. Subjects were 101 patients accepted
      for treatment at an Anxiety Disorders Clinic; 29 of the 101 patients participated
      in the inter-rater reliability study. Concordance between the instruments as
      measured by canonical correlation analysis was moderate for current (r = 0.69, p
      = 0.05) and for lifetime (r = 0.66, p = 0.05) diagnoses. Inter-rater reliability
      of the CIDI was perfect (overall intraclass kappa = 1.00), and of the SCAN was
      good (overall intraclass kappa = 0.67). It is concluded that although the two
      instruments made similar diagnostic distinctions, the clinical judgment involved
      in administering the SCAN resulted in the more moderate levels of agreement
      between the interviewer and observer than those found for the CIDI.

PMID- 7625962
TI  - Training to administer electroconvulsive therapy: a survey of attitudes and
      experiences.
AB  - Recent Royal Australian and New Zealand College of Psychiatrists guidelines
      regarding Electroconvulsive Therapy (ECT) call for "specific training in both the
      practical and theoretical aspects of ECT", involving provision of an "educational
      programme" by centres where ECT is administered, and "supervised administration
      of ECT prior to administering this treatment alone". This survey was undertaken
      to elicit the attitudes and experiences of current trainees in relation to
      training to administer ECT. It was found that ECT is given entirely by the
      registrars, that consultants are rarely or never present, and in most centres,
      training typically consists of registrars being supervised once or twice by
      another registrar, and thereafter administering ECT alone. Twenty percent of
      those who had given ECT, however, reported not being supervised the first time
      they administered it. Most trainees indicated limited theoretical teaching in
      this area, and almost none were aware of a formal training scheme at their
      respective hospitals. The College guidelines, as stated, address these issues,
      and priority should be given to their implementation.

PMID- 7625963
TI  - Tertiary prevention in mental health care: effects of group meetings for family
      caregivers.
AB  - Several series of discussion groups were conducted for people caring for
      relatives who suffer from chronic schizophrenia. Groups aimed to provide
      information from both experts and fellow caregivers about the illness and about
      coping techniques, and to foster emotional support within the peer group. Owing
      to the small number of subjects, statistical power was inadequate to test effects
      quantitatively; however, the responses of the family caregivers to structured
      follow-up questions indicated many gains from group attendance. Attendance and
      participation rates were high once subjects were engaged; positive outcomes were
      reported by the carers, and they actively sought feedback of their
      dissatisfactions with mental health services to the relevant decision-makers. The
      results are relevant both in the area of preventive mental health care for
      carers, and in promoting collaboration between carers and professionals.

PMID- 7625964
TI  - Family impacts on the development of the child.

PMID- 7625965
TI  - Multiple personality disorder in an intellectually disabled man: a case report.
AB  - The case of a young man with the dual diagnoses of severe intellectual handicap
      (IQ 30 and mental age 4 years) and Multiple Personality Disorder is presented.
      The intellectual handicap is probably due to hypoxia in infancy and the Multiple
      Personality Disorder follows prolonged physical and sexual abuse. The patient
      frequently switches between any of nine discrete but incompletely formed
      identities. Although some personalities seem more capable than others, all have
      similar levels of disability on testing. The diagnosis of psychiatric disorders
      coexistent with the intellectual handicap is hindered by the difficulty in
      separating psychiatric phenomena from the behavioural disturbances associated
      with the disability. Differential diagnosis and management are discussed.

PMID- 7625966
TI  - Mental health law and dangerousness.

PMID- 7625967
TI  - Antidepressants and side effects.

PMID- 7625968
TI  - Trinucleotide expansion in Tasmanian HD families.

PMID- 7625969
TI  - Thyroid abnormalities in chronic schizophrenia.

PMID- 7625970
TI  - Sleep fragmentation presenting with mood changes.

PMID- 7625971
TI  - Psychiatry, science and posttraumatic stress disorder.

PMID- 7625972
TI  - Does influenza cause schizophrenia? A five year review.
AB  - Over the last five years a body of literature has been generated concerning
      whether or not prenatal exposure to influenza results in an increased risk of
      developing schizophrenia in the exposed offspring. The studies are reviewed with
      respect to the traditional epidemiological criteria that help to define
      causality. There is a modest degree of consistency in support of an association
      between the 1957 influenza epidemic--and less so, for influenza epidemics in
      general--and later schizophrenia. Two cohort studies examining the 1957 epidemic
      do not support an association. The strength and specificity of the association
      remain weak. The proposed association draws coherence from the neurodevelopmental
      hypothesis of schizophrenia. Suggestions are made for future research that could
      add to our understanding of the putative association between influenza and
      schizophrenia.

PMID- 7625973
TI  - Rapid audit of clinical outcome and cost by computer.
AB  - A method to audit clinical outcome and cost was reliable over 17 years and 2000
      patients. Data gathered concerning 60 clinicians and 600 patients by a pilot
      computer system showed that inpatients with obsessive-compulsive disorder were
      more severely disabled than outpatients with the same disorder, and took twice
      the therapist time to treat. It was also found that some clinicians obtained
      three times the improvement per hour than did other clinicians with similar
      patients in the same unit. Outcome norms are accumulated for particular types of
      patient and treatment. A new computerised clinical audit system robust enough for
      general release will be available soon.

PMID- 7625974
TI  - A clinical perspective on SPECT.
AB  - The potential clinical utility of SPECT (Single Photon Emission Computed
      Tomography) brain imaging to clarifying certain diagnostic dilemmas faced by
      clinical psychiatrists is considered generally and is illustrated by several case
      vignettes. Three case histories consider dementia vs depressive pseudodementia,
      two the possibility of a cerebral vasculitis in patients with auto-immune
      conditions, and two whether the patient had a "type" of depression likely to
      benefit from a course of ECT. Published studies reviewing the utility of SPECT in
      dementia, depression, depressive "pseudodementia" and cerebral lupus are
      considered. It is suggested that SPECT is an important investigatory technique
      providing additional information that may assist some diagnostic decisions, while
      its utility in assisting other clinical decisions awaits clarification.

PMID- 7625976
TI  - A social skills group for boys with Asperger's syndrome.
AB  - A social skills group was conducted for 8 boys aged 8 to 12 years on a weekly
      basis for 14 sessions. In this descriptive paper we discuss the planning for the
      group, the teaching techniques used, the actual group process and a subjective
      assessment of outcomes. Possible directions for future interventions are also
      presented.

PMID- 7625975
TI  - The Western Australian child health survey: a pilot study.
AB  - A pilot survey of 200 households was undertaken to field test the survey
      instruments and trial the validation and calibration procedures for the Western
      Australian Child Health Survey (WACHS) conducted in 1992. This paper describes
      the background to the WACHS, the development of the instrumentation and the
      conduct of the pilot study. This survey aims to replicate and extend previous
      epidemiological surveys conducted in other countries, and to provide Australian
      norms for mental health morbidity in 4 to 16 year old children. The measurement
      of mental health was undertaken through the use of the Child Behaviour Checklist
      (CBCL). This screening instrument provided data on the prevalence of mental
      health morbidity and of specific mental disorders in 4 to 16 year olds. Its
      reliability and validity as a diagnostic indicator were checked through a
      clinical calibration technique. The pilot survey also permitted an examination of
      the sampling strategy adopted to ensure that the sample selected reflected
      "normality" in terms of expected trends and results. Modifications to the content
      of the questionnaires are described in light of both psychometric qualities of
      the data and comments from field interviewers and professionals who have examined
      the instrument. Finally, changes to data collection strategies are discussed.

PMID- 7625977
TI  - The mental health of Australians: can informative data be found?
AB  - The National Mental Health Policy has brought about a realisation that data on
      the mental health of Australians are sparse. This applies to the three levels of
      morbidity in the general population, the mental health component in general
      practice and the use of specialist services. This paper considers what
      epidemiological information is now needed to guide policy. There has probably
      never been a more opportune time to make a useful contribution to the nation's
      mental health services through well-planned epidemiological research.

PMID- 7625978
TI  - Misidentification syndromes in schizophrenia: case reviews with implications for
      classification and prevalence.
AB  - Misidentification syndromes represent false, delusionally-based identification of
      self and/or others. These are variants of the Capgras Syndrome. Although the
      frequency of misidentification syndromes in schizophrenic populations has not yet
      been established, the authors believe this syndrome is more prevalent than
      previously described. Seven of twenty-five (28%) consecutive patients admitted to
      a chronic clozapine unit with a variant of misidentification syndrome will be
      described. Their symptoms are categorised according to traditional
      classification, and Silva's proposed nomenclature. Problems inherent in these
      classifications are discussed. The need for a more systematic classification of
      misidentification syndromes is emphasised. Longitudinal studies of
      misidentification syndrome, and the development of a standardised assessment tool
      for clinicians who treat chronically psychotic patients, are encouraged.

PMID- 7625979
TI  - Self reports of the interaction between substance abuse and schizophrenia.
AB  - Fifty-three psychiatric hospital inpatients with a dual diagnosis of substance
      abuse and schizophrenia were given the Brief Symptom Inventory and the
      Schizophrenia/Substance Abuse Interview Schedule. Mean age was 29; 49 were men.
      Only 11% were employed. Forty percent abused mainly alcohol, 40% cannabis and 8%
      amphetamines; 20% abused more than one substance. Mean onset age of drug abuse
      was 16 years; schizophrenia was diagnosed a mean of 5 years later, and subjects
      had been admitted to hospital an average of 7 times since then. Most believed
      that drug abuse initiated or exacerbated their schizophrenia; 80% took drugs
      primarily to relieve dysphoria and anxiety. Amphetamines improved subjective well
      being significantly more than alcohol, but choice of drugs was determined mainly
      by price and availability. Only cannabis increased positive symptoms of
      schizophrenia and only amphetamines reduced negative ones. Effectively treating
      this population requires an integration of psychiatric and drug treatment
      services, ideally in a community context.

PMID- 7625980
TI  - Posttraumatic stress disorder after a bus accident.
AB  - There is insufficient information on the prevalence of posttraumatic stress
      disorder (PTSD) and other psychological reactions caused by surviving serious
      road accidents. This paper presents the assessments of 29 people who narrowly
      escaped death in a coach accident that killed eleven people. Their high
      vulnerability is clearly established, with 41% having PTSD, and 52% severe
      intrusion or avoidance phenomena, which included 31% who had both. The occurrence
      of psychological sequelae was associated with being currently distressed by
      another event, but not with the survivors' age, gender or acquaintance with
      people killed in the accident. Seeing bodies or witnessing the death of someone
      was the predominant cause of distress, both at the time of the accident and in a
      recurring way. Delayed reactions were evident, with the impact of several factors
      changing over time.

PMID- 7625981
TI  - Psychological sequelae of torture and trauma in Chilean and Salvadorean migrants:
      a pilot study.
AB  - Torture has existed since the earliest times, usually as public punishment prior
      to death. Today it is predominantly used in secret with the aim of destroying the
      individual's personality. The effects of torture include severe physical and
      psychological sequelae which have only recently come under scrutiny. In recent
      years many Chilean and El Salvadorean migrants have left their countries after
      being tortured and severely traumatised as a result of organised violence. The
      aim of this study was to pilot an investigation into the psychological sequelae
      of torture. Subjects were 30 Chileans and El Salvadoreans classified into three
      groups: torture, trauma and non-torture/trauma migrants. It was found to be
      feasible to access and interview survivors from a clinical research perspective
      without causing additional psychological morbidity. The subjects were interviewed
      and administered three scales: the Post-Traumatic Stress Disorder Scale, SCL-90
      R, and the Impact of Event Scale. The results from the scales and the descriptive
      data presented indicate some support for the hypothesis that torture survivors
      show higher levels of PTSD, psychosomatic impairment and stress response
      disturbance than the trauma and non-torture/trauma groups. Methodological issues
      are discussed. The strengths and limitations of this preliminary study are
      considered in relation to future research.

PMID- 7625983
TI  - Molecular pathogenesis of pituitary tumours.
AB  - Human pituitary tumours account for 10% of intracranial neoplasms. These tumours
      are usually sporadic and benign; malignant change and metastasis are extremely
      rare events. Autosomal dominant inheritance of MEN 1 accounts for a minority of
      pituitary tumours. Pituitary tumours have been found to be monoclonal in several
      studies. This would suggest that an intrinsic genetic pituitary defect is pivotal
      in the pathogenesis of these tumours. However, this concept does not exclude a
      role for the hypothalamus in the genesis of pituitary tumours; the trophic
      function of several hypothalamic peptides could promote initiation of the genetic
      event or facilitate a sequence of events leading to clonal expansion of the
      transformed cell. There has been modest progress made in the elucidation of the
      intrinsic genetic pituitary cell abnormalities that underlie pituitary
      tumorigenesis. A mutant alpha subunit of the Gs gene, designated gsp, which
      results in constitutive activation of adenylyl cylcase has been described in a
      subset of GH cell adenomas. Loss of genetic material on chromosome 11q13, the
      locus of the MEN 1 gene, is found in under 20% of pituitary adenomas, suggesting
      that inactivation of a tumour suppressor gene at this locus may be significant in
      the tumorigenic process. H-ras point mutations have been described in distant
      metastatic pituitary tumour secondaries. The genetic abnormalities described
      occur in only a small subset of pituitary tumours, indicating that the more
      significant tumour promoting genes are still to be discovered.

PMID- 7625982
TI  - Eating disorder patients at a NSW teaching hospital: a comparison with state-wide
      data.
AB  - The aim of the study was to present data which may be useful in deciding the type
      of services needed for eating disorder (ED) patients in New South Wales (NSW).
      The demographic and clinical characteristics of 155 patients consecutively
      admitted to a special ED unit at a major Sydney teaching hospital during the
      triennium 1989-1991 were documented and compared with relevant data from the
      State as a whole (709 admissions for ED to public facilities and 938 admissions
      for ED to private facilities during the same period). The findings are discussed
      in the light of information from overseas studies. Although a relatively large
      number of ED patients are admitted to hospitals in NSW, their short duration of
      stay suggests that many may receive inadequate treatment. The unit in the
      Department of Psychiatry at the Royal Prince Alfred Hospital (RPA), the largest
      public ED service in NSW, provides a special service for these patients. It is
      effective in bringing about nutritional restoration, with a duration of stay
      similar to those reported from centres overseas. Most referrals are tertiary, and
      there is a high prevalence of physical morbidity indicating a need for access to
      general medical facilities. Most serious physical complications occur in patients
      who can be identified by their chronicity and by the pattern of their behavioural
      disturbance. These various factors are considered in the formulation of
      recommendations for rationalizing the service.

PMID- 7625984
TI  - The role of the hypothalamus in pituitary neoplasia.
AB  - Although the role of the hypothalamus in the genesis of pituitary tumours has
      emerged to be one of promotion rather than of initiation, it remains of utmost
      clinical importance. The epidemiological finding that occult pituitary tumours
      are very frequent, but only very seldom progress towards clinical evidence and
      exceptionally to malignancy suggests that their aggressive potential is kept
      under control by a host of factors and that only the disruption of this complex
      mechanism can allow occult tumours to grow. Most of these factors are
      hypothalamic in origin, although the stimulatory action of releasing hormones can
      be enhanced and the inhibitory action of inhibiting hormones reduced by
      receptor/post-receptor alterations occurring in pituitary tumours. If in the case
      of oncogenic mutations the clone expansion might be sustained only by the
      constitutive activation of proliferative signals and not require the intervention
      of other promoting factors, in other circumstances promoting factors (such as an
      excess of stimulatory or lack of inhibitory factors) may be necessary for the
      expansion of the tumoral clone. The development of pituitary somatotrophinomas or
      corticotrophinomas in patients with GHRH or CRH hyperproduction, respectively,
      gives clinical evidence to the role of releasing hormones. The shrinking effect
      of dopamine or SRIH agonists on the tumour mass of prolactinomas and
      somatotrophinomas, respectively, and, conversely, the rapid tumour expansion of
      corticotrophinomas after the removal of the cortisol negative feedback by
      bilateral adrenalectomy are clinical proofs of the importance of inhibitory
      signals on tumour growth.

PMID- 7625985
TI  - Clinical-pathological correlations of pituitary tumours.

PMID- 7625986
TI  - Clinical features and differential diagnosis of pituitary tumours with emphasis
      on acromegaly.
AB  - Pituitary adenomas are frequently encountered, benign intracranial tumours.
      Clinically classified according to their capacity to produce and secrete
      hormones, pituitary tumours are diagnosed from the clinical manifestations and
      biochemical findings of specific pituitary hormone overproduction or of impaired
      pituitary function due to pressure on normal pituitary cells, the pituitary stalk
      or the hypothalamus. Additionally, the tumour may result in neurological
      manifestations due to its effect as an intracranial space-occupying lesion.
      Pituitary adenomas may present acutely with pituitary apoplexy after
      intrapituitary haemorrhage or infarction. The subsequent hypofunction of the
      pituitary with concomitant neurological sequelae of an expanding intracranial
      mass are often associated with excruciating headache, diplopia and visual field
      defects. Gradually developing neurological deficits or secondary endocrine
      failure over several years may precede the recognition of non-secretory tumours
      (30-40% of pituitary adenomas) as well as some of the hormone-producing adenomas,
      especially when they expand beyond the confines of the sella turcica.
      Asymptomatic masses occur in the pituitary in 5-27% of unselected autopsy series.
      About 10-20% of pituitaries imaged as part of a brain study contain lesions
      'consistent with a pituitary adenoma', with about half being pituitary adenomas
      ('incidentalomas'). Many advocate screening such cases for a wide spectrum of
      pituitary function abnormalities. Clinical judgement should be utilized to
      determine the extent of the work-up and the frequency of follow-up. Acromegaly, a
      clinical syndrome caused by excess growth hormone secretion, accounts for one
      sixth of resected pituitary tumours. This disorder leads to chronic progressive
      disability and a shortened life span, with approximately 50% of untreated
      acromegalic patients experiencing premature death. The prevalence of acromegaly
      has been estimated to range from 50 to 70 per million, with the age of diagnosis
      usually between the third and fifth decades. Conditions associated with
      acromegaly include glucose intolerance, diabetes mellitus, lipid abnormalities,
      cholelithiasis, goitre, and hyperthyroidism, respiratory complications,
      hypertension, cardiovascular disease, and calcium metabolism abnormalities. An
      association between acromegaly and cancer, especially of the colon, is now
      recognized. Epidemiological series have indicated that cancer of the colon,
      breast and other types of malignancy are a cause of death with increased
      frequency in acromegalics compared with expected rates. Hypopituitary symptoms
      secondary to the mass effect of macroadenomas in acromegalic patients are common.
      Among premenopausal women, menstrual irregularities and galactorrhoea have been
      reported in 40-70%, while more than half of the men complain of impotence and
      decreased libido.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7625988
TI  - Glycoprotein-secreting pituitary adenomas.
AB  - In the past, pituitary tumours that produce one or more of the glycoproteins
      (TSH, LH, FSH and alpha subunit) were thought to be rare. However, using modern
      immunocytochemical and molecular biology techniques, these tumours are being
      recognized with increasing frequency. Many of these tumours produce glycoprotein
      alpha and beta subunits in addition to intact glycoproteins. Hormone production
      is often low compared with tumour size, and serum hormone levels may not be
      elevated in these patients. Tumours that produce the gonadotrophins (LH or FSH)
      or alpha subunit account for the majority of clinically non-functioning pituitary
      adenomas. They do not cause a specific clinical syndrome, and usually present
      with symptoms of a large mass lesion and/or hypopituitarism. Optimal treatment of
      these tumours is often difficult. The initial approach is usually transsphenoidal
      surgery, followed by radiation therapy if there are symptoms due to residual
      tumour. Medical therapy of gonadotrophin and alpha subunit tumours may include
      the use of dopamine agonists or somatostatin analogues, although neither has been
      shown to consistently decrease tumour size. Preliminary trials with experimental
      GnRH antagonists suggest that these agents may be useful as adjuvant therapy of
      gonadotrophin tumours. Tumours that produce TSH are rare. Patients present with
      hyperthyroidism, which is often misdiagnosed as Graves' disease, as well as with
      symptoms of a pituitary mass lesion. Almost all TSH tumours secrete excess
      amounts of free alpha subunit. Optimal treatment of these tumours includes
      transsphenoidal surgery, followed by radiation therapy for residual tumour. The
      somatostatin analogue octreotide is effective in reducing excess TSH secretion
      from these tumours, and causes a reduction in tumour volume in a significant
      minority of patients.

PMID- 7625987
TI  - Advances in the diagnosis and treatment of Cushing's syndrome.
AB  - Excess endogenous glucocorticoid production, whether ACTH-dependent or ACTH
      independent, results in the classic clinical and biochemical picture of Cushing's
      syndrome. The diagnosis requires demonstration of an increased cortisol secretion
      rate, best achieved using determination of urinary free cortisol as an index. In
      mild cases, distinction from the hypercortisolism of pseudo-Cushing states may
      prove difficult. If the physician is in doubt, a dexamethasone/CRH test should be
      performed. Primary adrenal Cushing's syndrome can be diagnosed on the basis of
      undetectable plasma ACTH and the results of adrenal imaging procedures. ACTH
      dependent Cushing's syndrome can be differentiated using an oCRH test and imaging
      procedures. In the presence of a discrete pituitary lesion on imaging, a standard
      oCRH test with results consistent with such a lesion is sufficient to proceed to
      transsphenoidal surgery. In the absence of such a lesion or if the oCRH test is
      equivocal, simultaneous BIPSS with oCRH administration should be performed to
      distinguish between a pituitary or ectopic source. Surgical ablation is the
      treatment of choice for all types of Cushing's syndrome. In the 5% of cases with
      Cushing's disease in whom transsphenoidal surgery fails and in the 5% of cases in
      whom the disease recurs, repeat transsphenoidal surgery or radiation therapy in
      association with mitotane treatment are reasonable alternatives. Bilateral
      adrenalectomy effectively cures hypercortisolism if resection of the ACTH
      secreting tumour is unsuccessful and radiation/medical therapy fails.

PMID- 7625989
TI  - Clinical impact of hyperprolactinaemia.
AB  - Prolactinomas are benign, functioning pituitary tumours that cause reproductive
      dysfunction in men and women. PRL-secreting microadenomas have a benign clinical
      course and may even disappear without treatment. Absolute indications for
      treatment of hyperprolactinaemia include the need to restore fertility and the
      presence of a macroadenoma. A dopamine agonist is the treatment of choice
      regardless of tumour size and will normalize PRL and restore menses in the
      majority of cases. Hypogonadism induced by hyperprolactinaemia is associated with
      decreased spinal bone mineral content, but it is not clear whether the bone loss
      is progressive. Bone mass improves after treatment of the hyperprolactinaemia but
      does not normalize. The safety of chronic oestrogen therapy in women with
      hyperprolactinaemic amenorrhoea who are not desirous of fertility remains to be
      elucidated by ongoing clinical trials.

PMID- 7625990
TI  - Imaging of pituitary tumours.
AB  - In the neuroradiological study of pituitary tumours, second generation CT,
      dynamic CT and MRI provide information about the extent of the tumour and its
      anatomical relations with the surrounding tissues. Sometimes these techniques can
      distinguish primary anterior pituitary lesions from primary parasellar lesions
      with presentations in the sellar region. In general, contrast-enhanced MRI and
      dynamic CT are more sensitive than conventional CT for the diagnosis of pituitary
      microadenomas, as well as for the precise delineation of the parasellar invasion
      of macroadenomas. Radiological techniques usually cannot distinguish clinically
      non-functioning from functioning pituitary adenomas. BSIPSS is used for
      confirmation of the diagnosis of Cushing's disease as well as for the
      lateralization of pituitary microadenomas in Cushing's disease and some other
      anterior pituitary hyperfunctional states. Neurotransmitter-receptor ligand
      imaging by SPECT with 123I-IBZM and/or 111In-DTPA-octreotide characterizes the
      dopamine D2 and somatostatin receptor status of pituitary adenomas, respectively.
      In selected cases, these techniques may be used for the differential diagnosis of
      pituitary tumours as well as for the differential diagnosis of primary anterior
      pituitary lesions and primary parasellar lesions with presentations in the sellar
      region. If medical therapy of these tumours with receptor agonists is being
      considered, these techniques can help in selecting the first-line treatment.
      Furthermore, the effects of medical therapy on the tumour can be evaluated. The
      introduction of newer and more receptor-specific radioligands may expand the
      clinical use of these techniques in the future. The availability of PET for the
      clinical diagnosis of pituitary tumours is still limited, but promising results
      have been described.

PMID- 7625991
TI  - Surgical management of pituitary adenomas.
AB  - Surgical management of pituitary adenomas continues to be a safe and effective
      method, suitable for a large number of patients suffering from the effects of
      these lesions. Frequently surgery is just part of an overall programme that
      includes medical management and radiation therapy as well. It is important for
      the physicians and the patients to understand that surgery alone may not be
      totally successful, but that with careful follow-up and appropriate adjunctive
      management, patients with pituitary tumours may live normal lives, and may enjoy
      reversal of the endocrine and visual problems that had been caused by their
      tumours. Careful study of surgically managed patients has contributed to some of
      the advances that have occurred in the overall management of pituitary adenomas
      and in our understanding of their biology, pathophysiology and pathogenesis.

PMID- 7625992
TI  - Radiotherapy for pituitary tumours.

PMID- 7625993
TI  - An empirical method for assessing social problem solving in schizophrenia.
AB  - The development of a multimethod social problem-solving battery for schizophrenia
      is described. The battery is unique in that empirical methods were used
      throughout its development. The battery includes components that tap skills for
      response generation and response evaluation. The behavioral components of social
      problem solving are assessed in an extended role-play format. Individuals with
      schizophrenia and bipolar disorder, as well as nonpatient controls, completed the
      social problem-solving battery and cognitive measures. Subjects in the
      schizophrenia group performed more poorly than controls on measures of the
      ability to generate and evaluate response alternatives, as well as on the role
      play test. The two patient groups did not differ in performance on any of the
      social problem-solving components. Appropriateness of affect was the most
      powerful predictor of problem-solving effectiveness.

PMID- 7625994
TI  - The influence of external information on judgements of pain.
AB  - Two studies were performed to assess the relationship between estimates of
      subjective pain and a graduated ischemic pain stimulus. In the first, 20 subjects
      received a 7-minute pressure stimulus with a blood-pressure cuff and then rated
      their pain on a 0-5 scale. At three separate sessions, subjects saw either no
      feedback or a visual feedback slide that ostensibly depicted cuff pressure. The
      numbers were either accurate, too high, or too low. Subjective estimates of pain
      rose with increasing cuff pressure, but pain ratings were higher during high
      feedback conditions, and lower during low-feedback conditions than during either
      the no- or true-feedback conditions, which did not differ. Study 2, which
      evaluated subjective estimates of actual cuff pressure as well as pain,
      replicated these results. Both studies suggest that false information may alter a
      subject's report of pain and of the stimulus causing it.

PMID- 7625995
TI  - A staff manual to help developmentally disabled persons improve their work habits
      and productivity.
AB  - In keeping with new directions for Behavior Modification, this article presents a
      treatment manual that has evolved over the past dozen or so years from our
      research program on vocational habilitation with developmentally disabled
      persons. The manual presents staff-managed and self-management strategies for
      helping these people improve work habits and productivity in various settings.
      The manual was written for front-line staff working with developmentally disabled
      clients. Strategies are presented as a checklist, making it easy to select the
      most appropriate components for each client and work setting. The guidelines are
      supported by research. The manual has been used in numerous training seminars,
      and feedback has been positive. In a workshop at the 1990 Conference of the
      Florida Association for Behavior Analysis, for example, mean rating of the manual
      by participants was 4.5 on a 5-point scale.

PMID- 7625996
TI  - Promoting academic performance in inattentive children. The relative efficacy of
      school-home notes with and without response cost.
AB  - The present study examined the effectiveness of two different school-home notes
      for increasing academic productivity and appropriate classroom behavior in five
      inattentive children. Using an alternating treatments design, students received a
      school-home note with or without response cost. Both notes required teachers to
      evaluate students and required parents to provide consequences on a daily basis.
      The notes differed as to whether reprimands and response cost were included. The
      results indicated that on-task behavior and academic work completion improved in
      all five elementary school-aged children. The majority of subjects achieved
      greater improvements in on-task behavior with the response-cost component added
      to the school-home note.

PMID- 7625998
TI  - Lack of association of G-protein beta 2- and gamma 2-subunit N-terminal fragments
      provides evidence against the coiled-coil model of subunit-beta gamma assembly.
AB  - The association between peptides from bovine G-protein beta 2- and gamma 2
      subunits was studied by CD spectroscopy and cross-linking. Both peptides had
      approximately 25% stable alpha-helical structure at 25 degrees C, but there was
      no increase on mixing subunits as expected for coiled-coil formation. Also,
      disulphide cross-linking gave more beta 2 beta 2 homodimer than beta 2 gamma 2
      heterodimer. These data do not support the proposed N-terminal coiled-coil model
      of beta gamma-subunit association.

PMID- 7625999
TI  - Differential calcium dependence in the activation of c-Jun kinase and mitogen
      activated protein kinase by muscarinic acetylcholine receptors in rat 1a cells.
AB  - Carbachol stimulation of the muscarinic acetylcholine m1 receptor (m1R), stably
      expressed in Rat 1a fibroblasts, resulted in a calcium-dependent activation of c
      Jun kinase (JNK). Stimulation of the muscarinic acetylcholine m2 receptor (m2R),
      stably expressed in Rat 1a fibroblasts, resulted in a G1-mediated activation of
      JNK that was weak relative to that observed with the m1R. Chelation of calcium
      inhibited the m2R-mediated activation of JNK but not the robust m2R stimulation
      of mitogen-activated protein kinase (MAPK) activity. These findings demonstrate a
      role for the second messenger, calcium, in the differential regulation of the
      activity of JNK and MAPK in Rat 1a cells.

PMID- 7626000
TI  - Evaluation of the use of the luciferase-reporter-gene system for gene-regulation
      studies involving cyclic AMP-elevating agents.
AB  - The effects of cyclic AMP (cAMP)-elevating agents on the activity of cis-acting
      gene promoter sequences are frequently studied using the luciferase-reporter-gene
      system. The aim of the present study was to assess whether cAMP-elevating agents
      induce any changes in the level of luciferase activity independently of a
      transcriptional activation of promoter elements. Chloramphenicol
      acteyltransferase (CAT) and luciferase reporter genes under the control of the
      same promoter elements were transiently expressed in primary cultures of human
      vascular smooth-muscle cells. Transfected cells were treated with a cell
      permeable and non-hydrolysable cAMP analogue, 2'-O-monobutyryl-8-bromo cAMP, or
      with the cAMP-elevating agents forskolin and prostaglandin E1 (PGE1). Forskolin
      and PGE1 induced a significant increase in the level of luciferase activity, but
      had no effect on CAT activity. Conclusions based solely on the use of the
      luciferase-reporter-gene system in studies involving promoter activation by cAMP
      elevating agents could therefore be misleading.

PMID- 7626001
TI  - Characterization of the endogenous carnitine transport and expression of a rat
      renal Na(+)-dependent carnitine transport system in Xenopus laevis oocytes.
AB  - L-Carnitine transport was characterized in Xenopus laevis oocytes before and
      after injection of mRNA isolated from rat renal cortex. Non-injected oocytes
      revealed endogenous Na(+)-dependent transport of L-carnitine. After injection of
      15 ng of rat kidney mRNA, the Na(+)-dependent L-carnitine transport increased 2-3
      fold, reaching maximal activity after 5-6 days. The expressed carnitine transport
      was maximal at pH 7.5, whereas the endogenous transport showed no clear maximum
      between pH 6.0 and 8.5. Kinetic analysis revealed apparent Km values for L
      carnitine of 66 microM for the endogenous and 149 microM for the expressed
      transport. Trimethyl-lysine and D-carnitine inhibited both the endogenous and the
      expressed transport. In contrast, L-acetylcarnitine, L-isovalerylcarnitine, L
      palmitoylcarnitine and butyrobetaine inhibited predominantly the expressed
      transport, whereas glycinebetaine had no inhibitory effect on either transport
      system. Size-fractionated rat renal-cortex mRNA (median size 2 kb) induced a 3
      fold higher L-carnitine transport than did unfractionated mRNA. These studies
      demonstrate that Xenopus laevis oocytes exhibit Na(+)-dependent L-carnitine
      transport and provide the basis for expression-cloning of a rat renal Na(+)
      dependent L-carnitine transport system.

PMID- 7625997
TI  - The regulation of tyrosine kinase signalling pathways by growth factor and G
      protein-coupled receptors.

PMID- 7626002
TI  - Identification and characterization of a novel human neutrophil protein related
      to the S100 family.
AB  - A rabbit polyclonal antibody raised against myeloid-related protein 8 (MRP-8), a
      protein of the S100 family, recognized another S100 protein (MRP-14) as well as a
      protein of 6.5 kDa (p6) in the cytosol of resting neutrophils. p6 was found to be
      a novel member of the S100 family. It consisted of two isoforms with pI values of
      6.2 (the minor form, p6a) and 6.3 (the major form, p6b) and constituted 5% of the
      total cytosolic proteins. Both isoforms were also demonstrated in the cytosol of
      monocytes, but not in lymphocytes, as previously shown for MRP-8 and MRP-14. Only
      the major isoform bound radioactive Ca2+, as also observed for MRP-8, whereas the
      different variants of MRP-14 were all labelled. On neutrophil activation with
      opsonized zymosan, a stimulant known to require extracellular Ca2+, 58% of p6a
      and 42% of p6b was translocated to the membrane. With phorbol 12-myristate 13
      acetate, a Ca(2+)-independent stimulant, no translocation was detected. This
      translocation pattern was similar to that observed with MRP-8 and MRP-14. In
      addition, p6, MRP-8 and MRP-14 were specifically associated with the cytoskeletal
      fraction of the membrane. The Ca(2+)-dependent translocation of the novel S100
      protein in parallel with MRP-8 and MRP-14 suggests a role for these proteins in
      regulating the Ca2+ signal to the membrane cytoskeleton and thus in regulating
      neutrophil activation.

PMID- 7626003
TI  - The effect of salt and site-directed mutations on the iron(III)-binding site of
      human serum transferrin as probed by EPR spectroscopy.
AB  - The effects of site-directed mutation and salt on the iron(III)-binding site of
      the recombinant half-molecule of the N-terminal lobe (hTf/2N) of human
      transferrin was studied by EPR spectroscopy. Changes were observed in the EPR
      spectra of all variants investigated (D63S, D63C, G65R, K206Q, H207E, H249E,
      H249Q, K296E and K296Q) compared with that of the wild-type protein. The most
      pronounced changes in the metal site were caused by replacement of the
      coordinating residues, Asp-63 and His-249, and the non-coordinating residue Lys
      296, which is located in the hinge region of the iron-binding cleft. The EPR
      spectral changes from replacement of other non-coordinating residues were more
      subtle, indicating small changes in Fe3+ coordination to the protein. The EPR
      spectrum of variant G65R suggests that it adopts two distinct conformations in
      solution, one in which the two domains forming the iron-binding cleft are closed
      and one in which they are open; in the latter instance Asp-63 is no longer
      coordinated to the Fe3+. Chloride-binding studies on hTf/2N, K206Q, H207E, K296Q
      and K296E showed similar binding isotherms, indicating that none of the hinge
      region residues replaced, i.e. Lys-206, His-207 or Lys-296, are the sites of
      chloride binding. The results show that the coordination environment of the Fe3+
      is sensitive to structural changes from site-directed mutation of both remote and
      coordinated residues and also to chloride-binding and ionic strength effects.

PMID- 7626004
TI  - Mistranslation of a TGA termination codon as tryptophan in recombinant platelet
      derived growth factor expressed in Escherichia coli.
AB  - The mature 109-amino-acid human platelet-derived growth factor B (PDGF-B) peptide
      is derived by intracellular processing from a 241-amino-acid precursor
      synthesized in mammalian cells, with removal of 81 N-terminal and 51 C-terminal
      amino acids. In order to produce directly the mature 109-amino acid PDGF-B
      peptide as a recombinant protein in Escherichia coli, a CGA codon at position 110
      of a DNA sequence encoding the full-length precursor form of PDGF-B was converted
      into the translation termination codon TGA by in vitro mutagenesis. Expression of
      this DNA via a plasmid vector in E. coli resulted in production of two distinct
      PDGF-B proteins having apparent molecular masses of 15 and 19 kDa, with the
      latter species predominating. Structural characterization employing N- and C
      terminal amino acid sequencing and MS analyses indicated that the 15 kDa protein
      is the expected 109-amino-acid PDGF-B, and that the 19 kDa protein represents a C
      terminal extended PDGF-B containing 160 amino acids. Characterization of a unique
      tryptic peptide derived from the 19 kDa protein revealed that this longer form of
      PDGF-B results from mistranslation of the introduced TGA termination codon at
      position 110 as tryptophan, with translation subsequently proceeding to the
      naturally occurring TAG termination codon at position 161. Owing to the high rate
      of translation readthrough of TGA codons in this and occasionally other proteins,
      it appears that the use of TGA as a translation termination codon for proteins to
      be expressed in E. coli should be avoided when possible.

PMID- 7626005
TI  - Processing of iduronate 2-sulphatase in human fibroblasts.
AB  - Iduronate 2-sulphatase (IDS) is a lysosomal enzyme involved in degradation of
      dermatan sulphate and heparan sulphate. Antigenic material was obtained either by
      purification of placental IDS (A and B forms) or by expression of three different
      fusion peptides in Escherichia coli allowing the production of five specific
      antibodies. Pulse-chase-labelling experiments in over-expressing fibroblasts
      showed poor IDS processing but large amounts of precursors were secreted into the
      medium. The endocytosis of the 35S- or 33P-labelled precursors by deleted
      fibroblasts together with glycosylation studies and proteolysis inhibition by
      leupeptin allowed better elucidation of IDS maturation. The initial 73-78 kDa
      form is converted into a phosphorylated 90 kDa precursor after modification of
      its oligosaccharide chains in the Golgi apparatus. This precursor is processed by
      proteolytic cleavage through various intermediates to a major 55 kDa
      intermediate, with the release of an 18 kDa polypeptide. Further proteolytic
      cleavage by a thiol protease gives the 45 kDa mature form containing hybrid and
      complex-type oligosaccharide chains.

PMID- 7626006
TI  - Breakdown of the stereospecificity of DD-peptidases and beta-lactamases with
      thiolester substrates.
AB  - With peptide analogues of their natural substrates (the glycopeptide units of
      nascent peptidoglycan), the DD-peptidases exhibit a strict preference for D-Ala-D
      Xaa C-termini. Gly is tolerated as the C-terminal residue, but with a
      significantly decreased activity. These enzymes were also known to hydrolyse
      various ester and thiolester analogues of their natural substrates. Some
      thiolesters with a C-terminal leaving group that exhibited L stereochemistry were
      significantly hydrolysed by some of the enzymes, particularly the Actinomadura
      R39 DD-peptidase, but the strict specificity for a D residue in the penultimate
      position was fully retained. These esters and thiolesters also behave as
      substrates for beta-lactamases. In this case, thiolesters exhibiting L
      stereochemistry in the ultimate position could also be hydrolysed, mainly by the
      class-C and class-D enzymes. However, more surprisingly, the class-C Enterobacter
      cloacae P99 beta-lactamase also hydrolysed thiolesters containing an L residue in
      the penultimate position, sometimes with a higher efficiency than the D isomer.

PMID- 7626008
TI  - Evidence for a Na+/Ca2+ exchanger in neuroblastoma x glioma hybrid NG108-15
      cells.
AB  - To determine whether NG108-15 cells contain a functional Na+/Ca2+ exchanger, we
      isotonically replaced extracellular Na+ with N-methyl-D-glucamine (NMG) and
      measured the effect on cytosolic Ca2+ concentration ([Ca2+]i) using the
      fluorescent Ca2+ indicator fura 2. Replacement with NMG alone had no effect on
      basal [Ca2+]i or the rise in [Ca2+]i evoked by 80 mM K+ or 10 microM bradykinin,
      but caused a larger [Ca2+]i increase when thapsigargin and carbonyl cyanide p
      trifluoromethoxyphenylhydrazone (FCCP) were added to the cells; this enhanced
      [Ca2+]i increase could be reversed by adding Na+ back to the bathing buffer. The
      elevation in [Ca2+]i induced by thapsigargin and FCCP was inversely proportional
      to extracellular Na+ concentration. Furthermore, the exchanger operated in the
      reverse mode, as measured by either [Ca2+]i change or 45Ca2+ uptake. An 810 bp
      cDNA fragment of the exchanger was amplified by PCR; it differed by a single
      amino acid residue from the corresponding segment of the rat brain Na+/Ca2+
      exchanger. These data suggest that a functioning Na+/Ca2+ exchanger exists in
      NG108-15 cells.

PMID- 7626007
TI  - Activation of the mitogen-activated protein kinase cascade by pertussis toxin
      sensitive and -insensitive pathways in cultured ventricular cardiomyocytes.
AB  - The involvement of pertussis toxin (PTX)-sensitive and -insensitive pathways in
      the activation of the mitogen-activated protein kinase (MAPK) cascade was
      examined in ventricular cardiomyocytes cultured from neonatal rats. A number of
      agonists that activate heterotrimeric G-protein-coupled receptors stimulated MAPK
      activity after exposure for 5 min. These included foetal calf serum (FCS),
      endothelin-1 (these two being the most effective of the agonists examined),
      phenylephrine, endothelin-3, lysophosphatidic acid, carbachol, isoprenaline and
      angiotensin II. Activation of MAPK and MAPK kinase (MEK) by carbachol returned to
      control levels within 30-60 min, whereas activation by FCS was more sustained.
      FPLC on Mono Q showed that carbachol and FCS activated two peaks of MEK and two
      peaks of MAPK (p42MAPK and p44MAPK). Pretreatment of cells with PTX for 24 h
      inhibited the activation of MAPK by carbachol, FCS and lysophosphatidic acid, but
      not that by endothelin-1, phenylephrine or isoprenaline. Involvement of G
      proteins in the activation of the cardiac MAPK cascade was demonstrated by the
      sustained (PTX-insensitive) activation of MAPK (and MEK) after exposure of cells
      to AlF4-. AlF4- activated PtdIns hydrolysis, as did endothelin-1, endothelin-3,
      phenylephrine and FCS. In contrast, the effect of lysophosphatidic acid on PtdIns
      hydrolysis was small and carbachol was without significant effect even after
      prolonged exposure. We conclude that PTX-sensitive (i.e. Gi/G(o)-linked) and PTX
      insensitive (i.e. Gq/Gs-linked) pathways of MAPK activation exist in neonatal
      ventricular myocytes. FCS may stimulate the MAPK cascade through both pathways.

PMID- 7626010
TI  - Structural and functional properties of heparin analogues obtained by chemical
      sulphation of Escherichia coli K5 capsular polysaccharide.
AB  - Capsular polysaccharide from Escherichia coli K5, with the basic structure (GlcA
      beta 1-4GlcNAc alpha 1-4)n, was chemically modified through N-deacetylation, N
      sulphation and O-sulphation [Casu, Grazioli, Razi, Guerrini, Naggi, Torri,
      Oreste, Tursi, Zoppetti and Lindahl (1994) Carbohydr. Res. 263, 271-284].
      Depending on the reaction conditions, the products showed different proportions
      of components with high affinity for antithrombin (AT). A high-affinity
      subfraction, M(r) approx. 36,000, was shown by near-UV CD, UV-absorption
      difference spectroscopy and fluorescence to cause conformational changes in the
      AT molecule very similar to those induced by high-affinity heparin. Fluorescence
      titrations demonstrated about two AT-binding sites per polysaccharide chain, each
      with a Kd of approx. 200 nM. The anti-(Factor Xa) activity was 170 units/mg,
      similar to that of the IIId international heparin standard and markedly higher
      than activities of previously described heparin analogues. Another preparation,
      M(r) approx. 13,000, of higher overall O-sulphate content, exhibited a single
      binding site per chain, with Kd approx. 1 microM, and an anti-(Factor Xa)
      activity of 70 units/mg. Compositional analysis of polysaccharide fractions
      revealed a correlation between the contents of -GlcA-GlcNSO3(3,6-di-OSO3)-
      disaccharide units and affinity for AT; the 3-O-sulphated GlcN unit has
      previously been identified as a marker component of the AT-binding
      pentasaccharide sequence in heparin. The abundance of the implicated disaccharide
      unit approximately equalled that of AT-binding sites in the 36,000-M(r)
      polysaccharide fraction, and approached one per high-affinity oligosaccharide
      (predominantly 10-12 monosaccharide units) isolated after partial
      depolymerization of AT-binding polysaccharide. These findings suggest that the
      modified bacterial polysaccharide interacts with AT and promotes its
      anticoagulant action in a manner similar to that of heparin.

PMID- 7626009
TI  - Differential activation of heat-shock and oxidation-specific stress genes in
      chemically induced oxidative stress.
AB  - Post-ischaemic reperfusion increases the level of the major heat-shock (stress)
      protein hsp 70 and of its mRNA by transcriptional mechanisms, and activates the
      binding of the heat-shock factor HSF to the consensus sequence HSE. In common
      with CoCl2 treatment, post-ischaemic reperfusion increases the level of haem
      oxygenase mRNA, an indicator of oxidative stress, but CoCl2 does not seem to
      induce the expression of the hsp 70 gene [Tacchini, Schiaffonati, Pappalardo,
      Gatti and Bernelli-Zazzera (1993) Lab. Invest. 68, 465-471]. Starting from these
      observations, we have now studied the expression of two genes of the hsp 70
      family and of other possibly related genes under conditions of oxidative stress.
      Three different chemicals, which cause oxidative stress by various mechanisms and
      induce haem oxygenase, enhance the expression of the cognate hsc 73 gene, but do
      not activate the inducible hsp 70 gene. Expression of the other genes that have
      been studied seems to vary in intensity and/or time course, in relation to the
      particular mechanism of action of any single agent. The pattern of induction of
      the early-immediate response genes c-fos and c-jun observed during oxidative
      stress differs from that found in post-ischaemic reperfused livers. Oxidative
      stress-inducing agents do not promote the binding of HSF to its consensus
      sequence HSE, such as occurs in heat-shock and post-ischaemic reperfusion, and
      fail to activate AP-1 (activator protein 1). With the possible exception of
      Phorone, the oxidative stress chemically induced in rat liver activates NFkB
      (nuclear factor kB) and AP-2 (activator protein 2) transcription factors.

PMID- 7626012
TI  - Functional properties of a sarcoplasmic reticulum Ca(2+)-ATPase with an altered
      Ca(2+)-binding mechanism.
AB  - Treatment of sarcoplasmic reticulum vesicles with diethylpyrocarbonate in the
      presence of a large excess of reagent, at pH 6.2 and at room temperature, reveals
      both a fast- and a slow-reacting population of protein residues. The loss of the
      Ca(2+)-ATPase activity is mainly associated with the fast-reacting population
      being partially sensitive to hydroxylamine. There is also an effect on the Ca(2+)
      binding mechanism. Shorter derivatization times (5 min) produce a loss of the
      positive cooperativity of Ca2+ binding. When the treatment was prolonged for 30
      min there was an additional decrease in the overall Ca2+ affinity. Curve-fitting
      procedures applied to the non-cooperative binding isotherms provide the
      equilibrium constants for the two Ca2+ sites, although they cannot discriminate
      between interacting and independent site mechanisms. Prestationary kinetics
      assays show 2 Ca2+:1 ATP ratios, at any extent of Ca2+ saturation, indicating
      that the Ca2+ sites are not independent. The Ca2+ dissociation profile after
      derivatization shows a decrease in the dissociation constant for the release of
      the second Ca2+, which is consistent with interacting sites. Isotopic exchange
      experiments show fast and slow components of equal amplitude even at
      subsaturating Ca2+ concentrations, which is incompatible with independent binding
      sites. The experimental data suggest a modification of the equilibrium binding
      constants making them more similar, but keeping the interacting character. The
      structural position of the external (cytoplasmic) and the internal (lumenal) Ca2+
      sites remains unaltered in the absence of positive cooperativity.

PMID- 7626011
TI  - Differential regulation of von Willebrand factor exocytosis and prostacyclin
      synthesis in electropermeabilized endothelial cell monolayers.
AB  - We have developed a system to permeabilize human umbilical vein endothelial cells
      in monolayer culture by application of a high-voltage electric field. The
      permeabilized preparation allows access of small molecules (M(r) < 1000) without
      loss of large cytosolic proteins. Electropermeabilized cells exocytose highly
      multimeric von Willebrand factor from secretory granules in response to added
      Ca2+ (EC50 = 0.8 +/- 0.02 microM), with levels comparable with those observed on
      stimulation of intact endothelial cells by physiological agonists. MgATP2-
      potentiates Ca(2+)-driven von Willebrand factor secretion. Other nucleoside
      triphosphates, but not non-hydrolysable analogues, can replace ATP.
      Electropermeabilized cells also synthesize and release prostacyclin in response
      to added Ca2+ (EC50 = 0.3 +/- 0.08 microM), but nucleoside triphosphates markedly
      inhibit, whereas nonhydrolysable GTP analogues increase, Ca(2+)-driven
      prostacyclin synthesis. We conclude that elevation of the intracellular [Ca2+] is
      sufficient to cause efficient exocytosis of von Willebrand factor from
      permeabilized cells, despite evidence that additional second messengers are
      needed in intact cells. We find no evidence in endothelial cells for a guanine
      nucleotide-binding protein promoting exocytosis, although one is clearly involved
      in stimulating Ca(2+)-driven prostacyclin synthesis.

PMID- 7626013
TI  - Purification and characterization of citrate synthase isoenzymes from Pseudomonas
      aeruginosa.
AB  - Two types of citrate synthase (CS) have been purified from Pseudomonas
      aeruginosa, a 'large' form (CSI) and a 'small' form (CSII). The M(r)s of the CSI
      and CSII isoenzymes were determined to be 240,000 +/- 16,000 (mean +/- S.E.M.)
      and 80,300 +/- 3800 respectively. Chemical cross-linking of the native enzymes
      with either dimethyl suberimidate or glutaraldehyde followed by electrophoretic
      analysis by SDS/PAGE showed that CSI is a hexamer and CSII is a dimer. SDS/PAGE
      showed that CSI and CSII each consist of a single subunit type, of M(r) 42,000 +/
      2000 and M(r) 36,500 +/- 2000 respectively. CSI and CSII were also shown to be
      distinct kinetically, immunologically and in terms of their regulatory
      properties. It is suggested that the CS isoenzymes are products of different
      structural genes.

PMID- 7626014
TI  - A new pathway for the synthesis of the plant sulpholipid,
      sulphoquinovosyldiacylglycerol.
AB  - A new pathway is proposed for the biosynthesis of the plant sulpholipid,
      sulphoquinovosyldiacylglycerol. The pathway begins at UDP-glucose and involves
      the formation therefrom of UDP-4-ketoglucose-5-ene to which is subsequently added
      sulphite (or its metabolic equivalent). Evidence consistent with this pathway,
      rather than with the previously proposed 'sulphoglycolytic' route, was obtained
      from experiments with pea chloroplast preparations. The evidence included the
      failure of potential inhibitors of the sulphoglycolytic pathway to alter the rate
      of synthesis of sulpholipid and the stimulation of the incorporation of 35SO4(2-)
      into the latter by UTP. Radioactivity was effectively incorporated into
      sulpholipid from UDP-[14C]glucose and this radiolabelling was stimulated by the
      addition of methyl alpha-glucose-enide or of an enzyme system known to be forming
      (although not accumulating) UDP-4-ketoglucose-5-ene. This new pathway is also
      consistent with other data in the literature.

PMID- 7626015
TI  - Differentiation-dependent autophagy controls the fate of newly synthesized N
      linked glycoproteins in the colon adenocarcinoma HT-29 cell line.
AB  - Our previous results have demonstrated that, in undifferentiated human colon
      cancer HT-29 cells, a pool of glycoproteins bearing high-mannose oligosaccharides
      rapidly escapes the exocytic pathway to be degraded in the lysosomal compartment
      [Trugnan, Ogier-Denis, Sapin, Darmoul, Bauvy, Aubery and Codogno (1991) J. Biol.
      Chem. 266, 20849-20855]. We report here on the mechanism that governs this
      degradative pathway. Using pulse-chase experiments in combination with
      subcellular fractionation, we have observed that the sequestration of high
      mannose glycoproteins in lysosomes was impaired by drugs which interfere with the
      autophagic-lysosomal pathway. The accumulation of high-mannose glycoproteins in
      the lysosomal fraction was shown to be part of the general autophagic pathway
      constitutively expressed in undifferentiated cells, as independently measured by
      the sequestration of the cytosolic enzyme lactate dehydrogenase and electroloaded
      raffinose. Furthermore, when HT-29 cells were cultured under differentiation
      permissive conditions, the decreased accumulation of high-mannose glycoproteins
      in the lysosomal compartment was correlated with the decrease in autophagy.

PMID- 7626016
TI  - Squid spermiogenesis: molecular characterization of testis-specific pro
      protamines.
AB  - Cuttlefish spermiogenesis is characterized by a two-step nuclear protein
      transition: histones-->spermatid-specific protein (protein T)-->sperm protamine
      (protein Sp). A similar situation can be observed in another Cephalopod species,
      the squid Loligo pealeii. The protein T from Loligo consists of two structural
      variants, T1 and T2 (molecular masses: 10788 and 10791 Da respectively),
      phosphorylated to different degrees (2-6 phosphate groups). The primary
      structures of these two variants and of the protamine variant Sp2 were
      established from sequence analysis and mass spectrometric data of the proteins
      and their fragments. T1 and T2 are closely related proteins of 79 residues. The
      complete structural identity of the C-terminal domain (residues 22-79) of protein
      T2 with the sperm protamine Sp2 (molecular mass 8562 Da, 58 residues) strongly
      suggests that the testis-specific protein T2 is indeed the precursor of the
      protamine. The transition between the precursor protein T and protein Sp results
      from a hydrolytic cleavage similar to that found in many proteins that are
      synthesized as precursors. The processing mechanism involves the specific
      cleavage of a Gly-Arg bond in the sequence Met/Leu18-Lys-Gly-Gly-Arg-Arg23.
      Furthermore, the study provides molecular evidence on the taxonomic relationship
      between Loligo and Sepia.

PMID- 7626018
TI  - Complete nucleotide sequence of the gene encoding bacteriophage E endosialidase:
      implications for K1E endosialidase structure and function.
AB  - Bacteriophage E specifically recognizes and infects strains of Escherichia coli
      which display the alpha-2,8-linked polysialic acid K1 capsule. Bacteriophage E
      endosialidase, which is thought to be responsible for initial absorption of the
      phage to the host bacterium, was purified, and the N-terminal amino acid
      sequences of the polypeptide monomer and cyanogen bromide fragments were
      determined. Synthetic oligonucleotide probes were designed from the N-terminal
      amino acid sequences and used to identify restriction fragments of bacteriophage
      E DNA encoding the endosialidase. The primary nucleotide sequence of the
      bacteriophage E endosialidase gene contains an open reading frame encoding a 90
      kDa polypeptide which is processed to give a mature 74 kDa protein. The native
      enzyme is probably a trimer of identical 74 kDa subunits. In the bacteriophage E
      genome the K1E endosialidase open reading frame is preceded by a putative
      upstream promoter region with homology to a bacteriophage SP6 promoter. A central
      region of 500 amino acids of the deduced protein sequence of the K1E
      endosialidase was found to have 84% identity to K1F endosialidase. Both
      endosialidases contain two copies of a sialidase sequence motif common to many
      bacterial and viral sialidases. These sequences flank the region of greatest
      identity between the two endosialidase forms, which suggests that this central
      domain is involved in binding and hydrolysis of the polysialic acid substrate.

PMID- 7626017
TI  - Structure of the human aggrecan gene: exon-intron organization and association
      with the protein domains.
AB  - The complete exon-intron organization of the human aggrecan gene has been
      defined, and the exon organization has been compared with the individual domains
      of the protein core. A yeast artificial chromosome containing the aggrecan gene
      was selected from the Centre d'Etude du Polymorphisme Humaine yeast artificial
      chromosome library. A cosmid sulibrary was created from this, and direct
      sequencing of individual cosmids was used to provide the exon-intron
      organization. The human aggrecan gene was found to be composed of 19 exons
      ranging in size from 77 to 4224 bp. Exon 1 is non-coding, whereas exons 2-19 code
      for a protein core of 2454 amino acids with a calculated mass of 254379 Da.
      Intron 1 of the gene is at least 13 kb. Overall, the sizes of the 18 introns
      range from 0.5 to greater than 13 kb. Each intron begins with a GT and ends with
      an AG, thus obeying the GT/AG rule of splice-junction sequences. The entire
      coding region is contained in 39.4 kb of the gene. The organization of exons is
      strongly related to the specific domains of the protein core. The A loop of G1
      and the interglobular domain are encoded by exons 3 and 7 respectively. The B and
      B' loops of G1 are encoded by exons 4-6, and those of G2 are encoded by exons 8
      10. These sets of exons, coding for the B and B' loops, are identical in size and
      organization. This is supported by the intron classes associated with these
      exons. Exon 11 codes for the 5' half of the keratan sulphate-rich region, and
      exon 12 codes for the 3' half of the keratan sulphate-rich region as well as the
      entire chondroitin sulphate-rich region. G3 is encoded by exons 13-18, including
      the alternatively spliced epidermal growth factor-like and complement regulatory
      protein-like domains. The correspondence between the exon organization and the
      protein domains argues strongly for modular assembly of the aggrecan gene.

PMID- 7626019
TI  - A novel procedure for the rapid isolation of surfactant protein A with retention
      of its alveolar-macrophage-stimulating properties.
AB  - Previous studies have shown that surfactant protein A (SP-A) derived from
      alveolar-proteinosis patients activates rat alveolar macrophages. However, it is
      not known if normal rat, dog and human SP-A can also stimulate alveolar
      macrophages. As alveolar-proteinosis SP-A has a slightly different structure from
      ordinary SP-A, it would be possible that the ascribed alveolar-macrophage
      stimulating properties of SP-A are restricted to alveolar-proteinosis SP-A. To
      clarify this issue, we isolated SP-A from normal rat and dog pulmonary
      surfactants, using the same isolation technique commonly used for the isolation
      of alveolar-proteinosis SP-A, i.e. by butanol precipitation. In contrast with
      human alveolar-proteinosis SP-A, rat and dog SP-A obtained thus could not
      activate rat alveolar macrophages to produce oxygen radicals or enhance the
      phagocytosis of fluorescein isothiocyanate-labelled herpes simplex virus.
      However, rat, dog and normal human SP-A isolated by a novel method, involving
      extraction from pulmonary surfactant by using n-octyl beta-D-glucopyranoside and
      subsequent purification by cation-exchange chromatography, were able to elicit an
      oxidative burst in rat as well as normal human alveolar macrophages. In addition,
      dog and rat SP-A obtained thus stimulated the phagocytosis of herpes simplex
      virus by rat alveolar macrophages. These findings indicate that normal human, rat
      and dog SP-A have the same alveolar-macrophage-stimulating properties as human
      alveolar proteinosis SP-A. Dog and rat SP-A isolated by this novel method had the
      same Ca(2+)-dependent self-aggregation and lipid-aggregation properties as SP-A
      isolated by butanol precipitation. The new and milder isolation procedure yielded
      SP-A of high purity, as judged by SDS/PAGE and ELISA.

PMID- 7626020
TI  - A 63 kDa phosphoprotein undergoing rapid dephosphorylation during exocytosis in
      Paramecium cells shares biochemical characteristics with phosphoglucomutase.
AB  - We have enriched phosphoglucomutase (PGM; EC 5.4.2.2) approximately 20-fold from
      Paramecium tetraurelia cells by combined fractional precipitation with (NH4)2SO4,
      gel filtration and anion-exchange chromatography yielding two PGM peaks. Several
      parameters affecting PGM enzymic activity, molecular mass and pI were determined.
      Phosphorylation studies were done with isolated endogenous protein kinases. Like
      the 63 kDa phosphoprotein PP63, which is dephosphorylated within 80 ms during
      synchronous trichocyst exocytosis [Hohne-Zell, Knoll, Riedel-Gras, Hofer and
      Plattner (1992) Biochem. J. 286, 843-849], PGM has a molecular mass of 63 kDa and
      forms of identical pI. Since mammalian PGM activity depends on the presence of
      glucose 1,6-bisphosphate (Glc-1,6-P2) (which is lost during anion-exchange
      chromatography), we analysed this aspect with Paramecium PGM. In this case PGM
      activity was shown not to be lost, due to p-nitrophenyl phosphate-detectable
      phosphatase(s) (which we have separated from PGM), but also due to loss of Glc
      1,6-P2. Like PGM from various vertebrate species, PGM activity from Paramecium
      can be fully re-established by addition of Glc-1,6-P2 at 10 nM, and it is also
      stimulated by bivalent cations and insensitive to chelating or thiol reagents.
      The PGM which we have isolated can be phosphorylated by endogenous cyclic-GMP
      dependent protein kinase or by endogenous casein kinase. This results in three
      phosphorylated bands of identical molecular mass and pI values, as we have shown
      to occur with PP63 after phosphorylation in vivo (forms with pI 6.05, 5.95,
      5.85). In ELISA, antibodies raised against PGM from rabbit skeletal muscle were
      reactive not only with original PGM but also with PGM fractions from Paramecium.
      Therefore, PGM and PP63 seem to be identical with regard to widely different
      parameters, i.e. co-elution by chromatography, molecular mass, phosphorylation by
      the two protein kinases tested, pI values of isoforms, and immuno-binding. Recent
      claims that PP63 ('parafusin') would not be identical with PGM specifically in
      Paramecium are critically evaluated. Since some glycolytic enzymes are discussed
      as being associated with the Ca(2+)-release channel in muscle sarcoplasmic
      reticulum, and since sub-plasmalemmal Ca2+ stores in Paramecium closely resemble
      sarcoplasmic reticulum, a possible function of PP63/PGM in exocytosis regulation
      is discussed, particularly since dephosphorylation strictly parallels exocytosis.

PMID- 7626021
TI  - Non-muscle myosin II heavy chain has a cryptic cell-adhesion domain.
AB  - We have discovered a cryptic cell-adhesion domain in non-muscle myosin II heavy
      chain. A 205 kDa cell-adhesion-promoting polypeptide (p205) was extracted from
      BHK cells by Nonidet P-40 or Dounce homogenization. Adhesion to p205 was
      specifically inhibited by the peptide Gly-Arg-Gly-Asp-Ser-Pro, indicating a role
      for the Arg-Gly-Asp cell-adhesion motif. Purified p205 was identified as non
      muscle myosin II heavy chain, based on sequence analysis and on the cross
      reactivity of p205 with anti-(bovine trachea myosin) antibodies. Further
      experiments showed that the heavy chain of purified myosin II has cell-adhesion
      promoting activity in a cell-blotting assay, and cross-reacted with anti-p205
      antibodies. Finally, the adhesion domain was located in the tail portion of
      myosin II heavy chain, where an Arg-Gly-Asp-containing sequence can be found.

PMID- 7626022
TI  - Cell cycle-dependent regulation of elastin gene in cultured chick vascular smooth
      muscle cells.
AB  - A study was made of the relationship between elastin expression and the
      proliferative state of chick vascular smooth-muscle cells. Confluent cells of
      primary culture brought to a quiescent state by the deprivation of serum for 72 h
      exhibited a 5-, 3.5- and 2-fold increase in elastin synthesis, elastin mRNA level
      and transcriptional activity of elastin gene respectively over those in the
      proliferative state. On re-addition of serum in serum-deprived culture, cells
      started to proliferate, and elastin synthesis, its mRNA level and transcription
      of the gene decreased to the level of a proliferative state within 24 h,
      indicating that elastin expression in smooth-muscle cells was controlled by their
      growth states at least in part at a transcriptional level. A comparable increase
      in elastin mRNA level was observed when the cell growth was arrested by
      suspension culture for 72 h. When the cells were synchronized at the G1/S phase
      with thymidine/hydroxyurea treatment, elastin expression at the G1/S phase was
      greater than that at the G2/M phase during cell cycling. Elastin mRNA level at
      the G0 phase brought about by serum-deprivation or suspension culture
      predominated over that at the G1/S phase during cell cycling. These results
      indicate that gene expression of elastin and cell cycle are tightly coupled,
      which is independent of the presence of serum or adhesive state, and that elastin
      expression could be a biochemical marker for the growth states of smooth-muscle
      cells.

PMID- 7626023
TI  - Substitution of histidine-137 by glutamine abolishes the catalytic activity of
      the ribosome-inactivating protein alpha-sarcin.
AB  - The alpha-sarcin cytotoxin is an extracellular fungal protein that inhibits
      protein biosynthesis by specifically cleaving one phosphodiester bond of the 28 S
      rRNA. The His137 residue of alpha-sarcin is suggested to be involved in the
      catalytic activity of this protein, based on the observed sequence similarity
      with some fungal ribonucleases. Replacement of this residue by Gln (H137Q mutant
      variant of alpha-sarcin) abolishes the ribonuclease activity of the protein. This
      has been demonstrated for an homogeneous preparation of the H137Q alpha-sarcin by
      measuring its effect against both intact rabbit ribosomes and the homopolymer
      poly(A). The conformation of H137Q alpha-sarcin is highly similar to that of the
      wild-type protein, which has been analysed by CD and fluorescence spectroscopy.
      Both H137Q and wild-type alpha-sarcin exhibit identical CD spectra in the peptide
      bond region, indicating that no changes at the level of the secondary structure
      are produced upon mutation. Only minor differences are observed in both near-UV
      CD and fluorescence emission spectra in comparison to those of the wild-type
      protein. Moreover, H137Q alpha-sarcin interacts with phospholipid vesicles,
      promoting the same effects as the native cytotoxin. Therefore, we propose that
      His137 is part of the ribonucleolytic active site of the cytotoxin alpha-sarcin.

PMID- 7626024
TI  - Differences between the catalytic properties of recombinant human PC2 and
      endogenous rat PC2.
AB  - Human prohormone convertase PC2 was expressed in Xenopus oocytes and its
      properties were compared with those of the Type-2 endopeptidase of rat insulin
      secretory granules, previously identified as PC2 [Bennett, Bailyes, Nielson,
      Guest, Rutherford, Arden and Hutton (1992) J. Biol. Chem. 267, 15229-15236].
      Recombinant PC2 had the same substrate specificity as the Type-2 endopeptidase,
      cleaving at the CA-junction (Lys64, Arg65) of human des-31,32-proinsulin to
      generate insulin; little activity was found toward human des-64,65-proinsulin or
      proinsulin itself. Recombinant PC2 was maximally active in 5-7 mM Ca2+ (K0.5 =
      1.6 mM) whereas the Type-2 endopeptidase was maximally active in 0.5-1 mM Ca2+
      (K0.5 = 40 microM). Both enzymes had a pH optimum of 5.0-5.5 but the Type-2
      endopeptidase was active over a wider pH range. Two molecular forms of
      recombinant PC2 (71 kDa and 68 kDa) were found, both had an intact C-terminus but
      differed by the presence of the propeptide. The endogenous PC2 comprised several
      overlapping forms (size range 64-68 kDa), approximately two-thirds of which
      lacked C-terminal immunoreactivity. Part of the size difference between
      recombinant and endogenous PC2 was attributable to differences in N
      glycosylation. The different post-translational proteolytic modifications of
      recombinant and endogenous PC2 did not account for the different pH and Ca2+
      sensitivities shown by the enzymes. A modulating effect of carbohydrate on enzyme
      activity could not be excluded.

PMID- 7626025
TI  - Two thermostable type II restriction endonucleases from Icelandic strains of the
      genus Thermus: Tsp4C I (ACN/GT), a novel type II restriction endonuclease, and
      Tsp8E I, an isoschizomer of the mesophilic enzyme Bgl I (GCCNNNN/NGGC).
AB  - Sixteen isolates of thermophilic bacteria from the genus Thermus, isolated from
      neutral and alkaline hot water springs in the southwest region of Iceland, were
      tested for the presence of restriction endonucleases. Extracts from five of the
      isolates showed evidence of the presence of restriction endonuclease activity by
      producing discrete nucleotide fragments when incubated at 65 degrees C with
      lambda phage DNA. Two of the isolates (Tsp4C and Tsp8E) were found to have
      particularly high levels of restriction endonuclease activity, and the respective
      enzymes from these two Thermus isolates were partially purified and characterized
      and their recognition and cleavage sites were determined. Enzyme Tsp4C I is a
      novel Type II restriction endonuclease recognizing the interrupted palindromic
      tetranucleotide sequence ACNGT, where N can be any one of the four bases in DNA.
      Tsp4C I, which retains full enzyme activity when incubated for 10 min at
      temperatures up to 76 degrees C, hydrolyses the phosphodiester bond in both
      strands of a double-stranded DNA substrate between the third and fourth bases of
      the recognition sequence (ACN/GT), generating fragments with a single base 3'-OH
      overhang. Enzyme Tsp8E I is a thermostable isoschizomer of the mesophilic Type II
      restriction endonuclease Bgl I (GCCNNNN/NGGC) [Lee, Clanton and Chirikjiam (1979)
      Fed. Proc. 28, 294], generating fragments with a three base 3'-OH overhang.
      However, unlike Bgl I, Tsp8E I exhibits considerable thermal stability, retaining
      full enzyme activity when incubated for 10 min at temperatures up to 78 degrees
      C. Both Tsp4C I and Tsp8E I represent significant additions to the small but
      expanding list of the extremely thermostable restriction endonucleases.

PMID- 7626026
TI  - Isolation and characterization of the flavin-binding domain of flavocytochrome b2
      expressed independently in Escherichia coli.
AB  - Flavocytochrome b2 consists of two distinct domains. The N-terminal domain
      contains protohaem IX and the larger, C-terminal domain contains flavin
      mononucleotide (FMN). We describe here the isolation of the flavin-binding domain
      expressed in Escherichia coli independent of the cytochrome domain. The isolated
      domain is an efficient lactate dehydrogenase with ferricyanide as electron
      acceptor but reduces cytochrome c, the physiological oxidant for flavocytochrome
      b2, extremely poorly; electron transfer from the flavin-binding domain to the
      separately expressed cytochrome domain is undetectable. FMN reduction by lactate
      occurs as a single exponential process in the isolated flavin-binding domain, in
      contrast to the biphasic kinetics observed with native flavocytochrome b2.

PMID- 7626027
TI  - A comparison of the secondary structure of human brain mitochondrial and
      cytosolic 'malic' enzyme investigated by Fourier-transform infrared spectroscopy.
AB  - The secondary structure of human brain cytosolic and mitochondrial 'malic'
      enzymes purified to homogeneity has been investigated by Fourier-transform IR
      spectroscopy. The absorbance IR spectra of these two isoenzymes were slightly
      different, but calculated secondary-structure compositions were essentially
      similar (38% alpha-helix, 38-39% beta-sheet, 14% beta-turn and 9-10% random
      structure). These proportions were not affected by succinate, a positive effector
      of mitochondrial 'malic' enzyme activity. IR spectra indicate that the tertiary
      structures of human brain cytosolic and mitochondrial 'malic' enzymes are
      slightly different, and addition of succinate does not cause conformational
      changes to the tertiary structure of the mitochondrial enzyme. Thermal
      denaturation patterns of the cytosolic and mitochondrial enzymes, obtained from
      spectra recorded at different temperatures in the absence or presence of Mg2+,
      suggest that the tertiary structure of both isoenzymes is stabilized by bivalent
      cations and that the cytosolic enzyme possesses a more compact tertiary
      structure.

PMID- 7626028
TI  - Stimulation of inositol 1,4,5-trisphosphate production by peptides corresponding
      to the effector domain of different Rab3 isoforms and cross-linking of an
      effector domain peptide target.
AB  - Rab3 proteins are localized on secretory vesicles and appear to be involved in
      regulated exocytosis. We have previously shown that a modified peptide
      corresponding to the effector domain of the small molecular mass GTP-binding
      protein Rab3A, Rab3AAL, stimulates inositol 1,4,5-trisphosphate [Ins(1,4,5)P3]
      production and amylase release in digitonin-permeabilized pancreatic acini.
      Experiments using monoclonal antibodies reveal that the Rab3-like protein present
      in pancreatic acini is not the Rab3A isoform. However, since the putative
      effector domains of the four as yet known Rab3 proteins (A, B, C and D) differ
      only in the C-terminal four amino acid residues, Rab3A effector domain peptide
      could mimic the action of the pancreas-specific Rab3 isoform. In the present
      study we report that peptides corresponding to the different Rab3 isoforms
      stimulate both Ins(1,4,5)P3 production and amylase secretion with an order of
      potency Rab3B/D > Rab3AAL > Rab3A = Rab3C. For Rab3A, B/D and C effector domain
      peptides the concentrations causing half-maximal response (EC50) were 3, 0.2 and
      3 nM for Ins(1,4,5)P3 accumulation and 0.3, 0.02 and 0.3 nM for amylase release,
      respectively. A Rab1A effector domain peptide, Rab1AAL, and a scrambled peptide
      of Rab3AAL were less potent by several orders of magnitude in eliciting these
      responses compared with native Rab3 effector domain peptides. None of the
      peptides influenced Ins(1,4,5)P3 production and amylase release in intact acini.
      Cross-linking of 125I-Rab3B/D peptide to pancreatic acinar membranes showed a
      band at 70 to 75 kDa with maximum intensity at 75 kDa. Radiolabelling of the
      substrates could be displaced by unlabelled Rab3B/D peptide, and to a lesser
      extend by Rab3A peptide, whereas the scrambled peptide of Rab3AAL had no effect.
      These data suggest that phospholipase C and exocytosis might be regulated by
      Rab3B-or Rab3D-like proteins in pancreatic acinar cells. A 75 kDa protein that
      preferentially cross-linked to 125I-Rab3B/D effector domain peptide is a
      potential candidate as an effector protein of Rab3 effector domain peptides.

PMID- 7626029
TI  - Functional expression of the taste specific G-protein, alpha-gustducin.
AB  - The taste-specific G-protein alpha-subunit, alpha-gustducin, was expressed using
      a baculovirus based system. alpha-Gustducin was demonstrated to be myristoylated
      and was also palmitoylated in insect larval cells. Recombinant alpha-gustducin
      was purified to homogeneity. Neither receptors nor effectors that interact with
      gustducin in taste are known. However, alpha-gustducin has a close structural
      similarity to the visual G-protein, alpha-transducin. Therefore alpha-gustducin
      was reconstituted with components of the visual system to determine the degree of
      its functional similarity with alpha-transducin. Despite the fact that the
      sequences of alpha-gustducin and alpha-transducin share only 80% identity with
      each other, the interactions and functions of these two proteins were
      quantitatively identical. These included the interaction with receptor, bovine
      rhodopsin, with effector, bovine retinal cyclic GMP-phosphodiesterase, and with
      bovine brain and retinal G-protein beta gamma-heterodimers; receptor-catalysed
      GDP-GTP exchange and the intrinsic GTPase activity of alpha-gustducin and alpha
      transducin were also identical. Gi alpha which is 70% identical with alpha
      transducin interacts with different receptor and effector proteins and has very
      different guanine-nucleotide binding properties. Therefore, the functional
      equivalence of alpha-gustducin and alpha-transducin suggest that taste buds are
      likely to contain receptor and effector proteins that share many properties with
      their retinal equivalents.

PMID- 7626030
TI  - Anion dependence of bumetanide binding and ion transport by the rabbit parotid
      Na(+)-K(+)-2Cl- co-transporter: evidence for an intracellular anion modifier
      site.
AB  - The anion dependence of [3H]bumetanide binding and 22Na+ transport by the rabbit
      parotid Na(+)-K(+)-2Cl- co-transporter was studied in acinar basolateral membrane
      vesicles (BLMVs). Cl-, Br- and NO3- have a biphasic effect on binding consistent
      with the presence of two anion sites associated with the bumetanide binding
      event, a high-affinity stimulatory site and a lower-affinity inhibitory site. We
      show that formate shares only the stimulatory site and SO4(2-) only the
      inhibitory site. The initial rate of [3H]bumetanide binding was stimulated by
      formate or low [Cl-] and inhibited by SO4(2-) or high [Cl-], but the rate of
      [3H]bumetanide dissociation was not affected by the presence of these anions in
      the dissociation medium. However, when [3H]bumetanide was bound to BLMVs in the
      presence of formate its rate of dissociation was more than four times faster than
      when binding took place in the presence of Cl-. These observations indicate that
      the binding of bumetanide and the stimulatory anion are ordered such that the
      anion must necessarily bind first and subsequently cannot dissociate until after
      bumetanide dissociates. In zero-trans-flux experiments, extravesicular SO4(2-)
      and formate had no effect on 22Na+ transport via the co-transporter [Turner and
      George (1988) J. Membr. Biol. 102, 71-77]. Thus neither of the anion sites
      associated with bumetanide binding is a Cl- transport site. However, we show here
      that SO4(2-) inhibits transport when present in the intravesicular space. Since
      the BLMV preparation is predominantly oriented cytosolic-side-in, this
      observation indicates the existence of an inhibitory cytosolic anion modifier
      site. Our data suggest that this site is identical to the inhibitory anion site
      associated with bumetanide binding.

PMID- 7626031
TI  - Characterization of L-carnitine transport by rat kidney brush-border-membrane
      vesicles.
AB  - In the presence of a 100 mM Na+ gradient, transport of L-carnitine into rat renal
      brush-border-membrane vesicles was linear over 30 s and showed an overshoot at 5
      min. The uptake of L-carnitine was clearly less active in the presence of other
      cations such as Li+, K+, Cs+ or choline. In the presence of a Na+ gradient, L
      carnitine uptake after 20 s was much higher for chloride as an anion than for SCN
      , NO3-, gluconate or SO4(2-). In comparison with conditions with inside positive
      or no membrane potential, transport was higher in vesicles with an inside
      negative membrane potential, suggesting an electrogenic mechanism. The kinetic
      characterization of the Na(+)-dependent portion of L-carnitine transport revealed
      two transport systems with Km values of 17.4 +/- 3.9 microM and 15.0 +/- 6.0 mM,
      respectively. The transport could be inhibited in a concentration-dependent
      fashion by structural analogues such as butyrobetaine, L-acetylcarnitine,
      trimethyl-lysine and D-carnitine, but not by L-arginine or glycinebetaine.

PMID- 7626032
TI  - Synthesis and release of hyaluronic acid by Swiss 3T3 fibroblasts.
AB  - Hyaluronic acid (HA) and its synthesis were studied in intact Swiss 3T3 mouse
      fibroblasts and isolated membranes. HA chains in culture medium, attached to
      cells and in isolated membranes, were determined to possess average M(r) values
      of 5.2 x 10(6), 1.8 x 10(6) and 0.14 x 10(6) respectively. Log cells were
      determined to possess 680,000 HA molecules/cell, and to release 120,000 HA
      chains/h. The time required for intact cells to synthesize and release a complete
      HA chain was approximately 4 h, with elongation proceeding at a rate of 57
      dimers/min. The amount of cell-associated HA of various cell populations
      correlated strongly with their rate of HA release into culture media and with the
      HA synthetase activity determined for their membranes. Prevention of protein
      synthesis with cycloheximide decreased the rate of HA synthesis of log cells and
      HA synthetase activity of isolated membranes by 50% within 2-3 h. Because of the
      similarity between the biological lifetime of HA synthetase and the time required
      to synthesize a HA chain, we propose a model where each synthetase makes only one
      HA chain; after synthesis of a complete HA chain, HA synthetase activity is
      terminated as its HA chain is released from the cell.

PMID- 7626033
TI  - The src-family protein-tyrosine kinase p59hck is located on the secretory
      granules in human neutrophils and translocates towards the phagosome during cell
      activation.
AB  - The src-family protein-tyrosine kinase p59hck is mainly expressed in neutrophils;
      however, its functional role in these cells is unknown. Several other src-family
      members are localized on secretory vesicles and have been proposed to regulate
      intracellular traffic. We have established here the subcellular localization of
      p59hck in human neutrophils. Immunoblotting of subcellular fractions showed that
      approx. 60% of the p59hck per cell is localized on the secretory granules; the
      other 40% is distributed equally between non-granular membranes and the cytosol.
      Immunofluorescence of neutrophils and HL60 cells suggests that the p59hck
      positive granules are azurophil granules. Granular p59hck is highly susceptible
      to degradation by an azurophil-granule proteinase. Different forms of p59hck
      occur in the three subcellular compartments: a 61 kDa form is mainly found in the
      granules, a 59 kDa form is predominant in the non-granular membranes, whereas
      cytosolic p59hck migrates as a doublet at 63 kDa. During the process of
      phagocytosis-linked degranulation, induced by serum-opsonized zymosan in
      neutrophils or HL60 cells, granular p59hck translocates towards the phagosome.
      The subcellular localization of p59hck suggests that the enzyme could be involved
      in the regulation of the degranulation process.

PMID- 7626034
TI  - Regulation of myo-inositol transport during the growth and differentiation of
      thyrocytes: a link with thyroid-stimulating hormone-induced phospholipase A2
      activity.
AB  - The Vmax of myo-inositol transport increased 3-fold during epidermal growth
      factor (EGF)-induced growth and thyroid-stimulating hormone. (TSH)-induced
      differentiation in primary cultures of sheep and human thyrocytes. The Km
      remained unaltered. This up-regulation required the presence of insulin. The TSH
      induced rise in myo-inositol transport commenced 8 to 16 h after the initial
      stimulus and achieved a plateau at 24 h. In human thyrocytes the change in Vmax
      was accompanied by an increase in the steady-state levels of mRNA for the myo
      inositol transporter following treatment with either ligand. Examination of the
      metabolites of myo-inositol showed few significant changes after treatment of
      sheep thyrocytes with EGF for 24 h. This is consistent with maintenance of the
      intracellular concentration of myo-inositol as the cells enlarge in preparation
      for cell division. In TSH-treated cells, however, up-regulation of myo-inositol
      transport was linked with increased myo-inositol cycling across the cell
      membrane, increased phospholipase A2-mediated turnover of phosphatidylinositol
      and a concomitant increase in arachidonic acid turnover. Increased levels of myo
      inositol phosphates were also noted 24 h after TSH treatment. These results
      indicate the initiation of secondary signalling events many hours after the
      primary stimulus.

PMID- 7626035
TI  - Identification of a band-3 binding site near the N-terminus of erythrocyte
      membrane protein 4.2.
AB  - Protein 4.2 (P4.2) is a major component of the erythrocyte plasma membrane
      accounting for approx. 5% of total membrane protein. The major membrane binding
      site for P4.2 is contained within the cytoplasmic domain of band 3 (cdb3),
      although the precise location of the cdb3 binding site is not known. To identify
      the cdb3 binding site, we used synthetic P4.2 peptides (15-mers) that spanned the
      entire 721-amino-acid large isoform of P4.2, and determined the binding of these
      peptides to cdb3 in an in vitro binding assay. One peptide, P8
      (L61FVRRGQPFTIILYF), bound strongly to cdb3 and four others bound less strongly
      (P22, L271LNKRRGSVPILRQW; P27, G346EGQRGRIWIFQTST; P41, L556WRKKLHLTLSANLE; P48,
      I661HRERSYRFRSVWPE). These peptides have in common a cluster of two or three
      basic amino acid residues (arginine or lysine), in a region without nearby acidic
      residues. Cdb3 bound saturably to P8 with a Kd of 0.16 microM and a capacity of
      0.56 mol of cdb3 monomer/mol of P8. Use of overlapping synthetic peptides further
      defined the cdb3 site as being contained within V63RRGQPFTIILYF. Replacement of
      R64R with R64G, G64R or G64G almost completely abolished cdb3 binding, suggesting
      that R64R is essential for cdb3 binding. P8 competitively inhibited binding of
      purified human erythrocyte P4.2 to cdb3. In blot overlay assays, cdb3 bound to a
      23 kDa N-terminal P4.2 tryptic peptide containing V63RRGQPFTIILYF but not to
      other P4.2 tryptic peptides lacking this site. The V63RRGQPFTIILYF site is highly
      conserved in mouse and human erythrocyte P4.2 as well as between P4.2 and
      transglutaminase proteins, which are evolutionarily related to P4.2.

PMID- 7626036
TI  - Proteolytic processing of the alpha-subunit of rat endopeptidase-24.18 by furin.
AB  - Endopeptidase-24.18 (EC 3.4.24.18; meprin) is a multisubunit metallopeptidase of
      the astacin family. It is found in brush-border membranes of rodent kidney and
      human intestine. The membrane-bound enzyme is composed of alpha/beta dimers.
      Molecular cloning has shown that both subunits have a similar structural domain
      organization. Soluble alpha 2 dimers have also been observed in vivo and in
      transfected cells. The structures of all known alpha-subunits contain, upstream
      from the transmembrane domain, the sequence RXKR, which corresponds to the RXK/RR
      consensus sequence for specific cleavage by furin. In order to investigate the
      involvement of this putative cleavage site in the secretion process of
      endopeptidase-24,.18 alpha-subunit, we expressed in COS-1 cells rat alpha
      subunits in which residues R655 or S656 (within the sequence R652PKRS656) were
      mutated to valine or leucine respectively. In contrast to the wild-type protein,
      the alpha R655V and alphaS656L mutants were not secreted in the culture medium.
      Moreover, when cells expressing the alpha-subunit were infected with a furin
      encoding vaccinia virus, immunoblotting showed a shift of the major cell
      associated form of endopeptidase-24.18 alpha-subunit from 98 kDa to 85 kDa and an
      increase in the amounts of secreted alpha-subunit. This shift in molecular mass
      was not observed with the mutant alpha-subunits. As observed for the 98 kDa
      species, the 85 kDa cell-associated protein was sensitive to endoglycosidase H
      treatment, suggesting that the proteolytic cleavage occurred in the endoplasmic
      reticulum or in an early Golgi compartment. Similar experiments using PACE4 and
      PC5 instead of furin showed that these enzymes were not able to generate the 85
      kDa species. We conclude that furin is most probably the cellular enzyme involved
      in the proteolysis resulting in secretion of rat endopeptidase-24.18 alpha
      subunit.

PMID- 7626037
TI  - Over-expression and characterization of active recombinant rat liver carnitine
      palmitoyltransferase II using baculovirus.
AB  - The cDNA encoding rat liver carnitine palmitoyltransferase II (CPT-II) was
      heterologously expressed using a recombinant baculovirus/insect cell system.
      Unlike Escherichia coli, the baculovirus-infected insect cells expressed mostly
      soluble active recombinant CPT-II (rCPT-II). CPT activity from crude lysates of
      recombinant baculovirus-infected insect cells was maximal between 50 and 72 h
      post-infection, with a peak specific activity of 100-200 times that found in the
      mock- or wild-type-infected control lysates. Milligram quantities (up to 1.8 mg/l
      of culture) of active rCPT-II were chromatographically purified from large-scale
      cultures of insect cells infected with the recombinant baculovirus. The rCPT-II
      was found to be: (1) similar in size to the native rat liver enzyme
      (approximately 70 kDa) as judged by SDS/PAGE; (2) immunoreactive with a
      polyclonal serum raised against rat liver CPT-II; and (3) not glycosylated.
      Kinetic analysis of soluble rCPT-II revealed Km values for carnitine and
      palmitoyl-CoA of 950 +/- 27 microM and 34 +/- 5.6 microM respectively.

PMID- 7626038
TI  - Present situation of the analysis of Rh genes.

PMID- 7626039
TI  - Selective coupling of prostaglandin E receptor EP3D to multiple G proteins
      depending on interaction of the carboxylic acid of agonist and arginine residue
      of seventh transmembrane domain.
AB  - Prostaglandin E receptor EP3D is coupled to stimulation and inhibition of
      adenylate cyclase and stimulation of phosphatidylinositol turnover. To examine
      the roles of the interaction of the carboxylic acid of an agonist and its
      putative binding site, the arginine residue in the seventh transmembrane domain
      of EP3D, in receptor-G protein coupling, we have mutated the arginine to the non
      charged glutamine. TEI-3356, an EP3 agonist with a negatively charged the
      carboxylic acid, and TEI-4343, a non-charged methylester of TEI-3356, inhibited
      the forskolin-stimulated cAMP formation in the same concentration-dependent
      manner, but stimulation of basal cAMP formation and Ca2+ mobilization by TEI-4343
      was much lower than that by TEI-3356. In the mutant receptor, both TEI-3356 and
      TEI-4343 showed the inhibition of forskolin-stimulated cAMP formation in the same
      profile, but did not stimulate basal cAMP formation or Ca2+ mobilization. These
      findings suggest that the interaction between the carboxylic acid of agonist and
      the arginine residue is important in signal transduction for adenylate cyclase
      stimulation and Ca2+ mobilization but not for adenylate cyclase inhibition.

PMID- 7626040
TI  - Transdermal transport of DNA antisense oligonucleotides by electroporation.
AB  - Fluorescein-labeled antisense oligodeoxynucleotides (ODNs) corresponding to the
      promoters of the protooncogene c-myb (24-mer) and the oncogene c-myc (15-mer)
      were transported through the human skin in vitro by electroporation. Fluxes of
      6.4 +/- 2.1 pM/cm2* hr and 11.5 +/- 3.5 pM/cm2* hr, respectively, were achieved
      during exponential pulsing [tau pulse = 1.1ms, transdermal voltage (Uskin) = 80V]
      every five seconds. The flux for Uskin < 70V was undetectable, rapidly increased
      at 80V, but plateaued at higher values. Fluorescence imaging demonstrated that
      transport of the ODNs is concentrated in localized transport regions (LTRs)1
      approximately 30 microns in diameter.

PMID- 7626041
TI  - Interleukin-1 beta induces the synthesis of adenylyl cyclase in Swiss 3T3
      fibroblasts and MG-63 osteosarcoma cells.
AB  - In this study, the longer term (> or = 6 hours) effect of interleukin-1 beta on
      adenylyl cyclase activity was investigated in Swiss 3T3 and MG-63 cells. No
      change was evident after 6 hours but after 1, 7 or 15 day incubations a
      significant increase in basal (1.5- 2 fold) and NaF-stimulated (2-4 fold)
      adenylyl cyclase activity was observed in interleukin-1 beta pre-treated cell
      membranes compared with non pre-treated controls. The response to forskolin, a
      direct stimulus of adenylyl cyclase, was also significantly enhanced, indicating
      that the effect of interleukin-1 beta was targeted to the enzyme itself. This
      action of interleukin-1 beta was blocked by co-incubation with cycloheximide, an
      inhibitor of protein synthesis, which demonstrated that de novo protein synthesis
      was required. It is concluded that interleukin-1 induces the expression of
      adenylyl cyclase in 3T3 and MG-63 cells, leading to enhanced activation by NaF
      and forskolin.

PMID- 7626042
TI  - Oxygen tension influences DNA fragmentation and cell death in glucocorticoid
      treated thymocytes.
AB  - Internucleosomal DNA fragmentation and cell death induced by dexamethasone in rat
      thymocytes were inhibited when cells were cultured in 95% N2/5% CO2 atmosphere,
      in which oxygen was rapidly reduced to under 0.5%. DNA fragmentation was delayed
      by a less severe hypoxia in 5% oxygen whilst in cell cultured in high oxygen
      atmosphere (95% O2) cell death was increased. On the other hand, prolonged oxygen
      deprivation caused an increase of spontaneous apoptotic cell death. Hypoxia also
      inhibited DNA fragmentation induced by calcium ionophore A23187, but not by
      topoisomerase inhibitor camptothecin. These data support the hypothesis of the
      involvement of oxygen reactive species in calcium-mediated apoptosis and suggest
      a complex role of oxygen in the modulation of programmed cell death.

PMID- 7626043
TI  - Asynchronous dynamic changes of intracellular free Ca2+ and possible exocytosis
      in human tracheal gland cells induced by neutrophil elastase.
AB  - Measurements of the intracellular free calcium concentration [Ca2+]i in single
      cells of the human tracheal gland cell line MM 39 demonstrate dynamic changes in
      [Ca2+]i after their exposure to human neutrophil elastase (HNE). A heterogeneity
      in [Ca2+]i responses measured cell to cell in monolayer culture is evident: cells
      generate an initial [Ca2+]i peak rise with or without a delayed time (up to 180
      sec) followed either by a rapid return to baseline, asynchronous oscillations or
      a sustained plateau phase. From basal concentration of 85 +/- 15 nM, HNE (1
      microM) produces a [Ca2+]i increase of 91 +/- 66 nM in about 50% of responding
      cells. At lower concentrations of HNE (0.1 microM, 0.01 microM), the [Ca2+]i rise
      remains similar, but only 30-40% of the cells are responding. Pretreatment of
      cells with the recombinant elafin protein, a specific elastase inhibitor, reduces
      both the [Ca2+]i response to HNE and the number of responding cells. Electron
      microscopy observations reveal an increased number of secretory granules located
      beneath the cell plasma membrane after HNE treatment. These results suggest that
      intracellular [Ca2+]i changes may be associated to the HNE-induced exocytosis in
      human tracheal gland cells. These findings could have implications with regard to
      the pathogenesis of increased mucus secretion in human airway diseases.

PMID- 7626044
TI  - Characterisation of a gain-of-function mutant of poly(ADP-ribose) polymerase.
AB  - In order to examine the structure-function relationship of the poly (ADP-ribose)
      polymerase (PARP) catalytic domain, potential active-site residues in the
      catalytic domain have previously been described. Here, we have used mutagenesis
      with hydroxylamine to generate a random library of PARP mutants. The
      identification, overproduction in insect cells, purification and characterization
      of a gain-of-function mutant (L713F) is described. We show that the kcat of this
      mutant is increased over nine times compared to the wild-type enzyme; the Km for
      NAD+ is unchanged. The size and the branching structure of the ADP-ribose
      polymers are similar in both the wild-type and the mutant enzyme. This mutation
      may have an allosteric effect on the catalytic site and could be useful in
      analyzing the consequences of poly ADP-ribose overproduction in vivo on cell
      survival following DNA damage.

PMID- 7626045
TI  - The effect of hepatocyte growth factor on the behaviour of osteoclasts.
AB  - Hepatocyte growth factor (HGF) stimulates the growth, motility and morphogenesis
      of a variety of cell types, including hemopoietic progenitors. We found that HGF
      is a potent inhibitor of bone resorption by isolated rat osteoclasts. However, in
      the presence of the osteoblastic cell line UMR 106, it stimulated osteoclastic
      resorption. HGF also increased osteoclastic motility and spread area, over a
      similar concentration range. We detected no effect on osteoclast formation or
      survival. Our data suggest that HGF may be involved in the recruitment of
      osteoclasts to sites of bone resorption, but that during migration resorptive
      functions are suppressed. Once on resorptive sites, the osteoclast response to
      HGF is modulated by osteoblastic cells and the bone resorptive activity of
      osteoclasts may be stimulated accordingly.

PMID- 7626046
TI  - Direct detection of expanded (CAG/CTG) repeats in the myotonin-protein kinase
      genes of myotonic dystrophy patients using a high-stringency hybridization
      method.
AB  - Recent discoveries of genes containing (CAG/CTG) repeats as the causative genes
      for neuromuscular diseases suggest that trinucleotide repeat expansions are
      associated with a number of other neurodegenerative diseases, particularly in
      those showing genetic anticipation. In order to efficiently identify expanded
      trinucleotide repeats, we have developed a novel method using a single-stranded
      probe containing (CAG)55, which allows direct detection of expanded (CAG/CTG)
      repeats in the myotonin-protein kinase (Mt-PK) genes of patients with myotonic
      dystrophy without the need for any prior information of chromosomal localizations
      of the disease genes. This method is expected to be useful for identifying novel
      genes for diseases associated with expanded (CAG/CTG) repeats.

PMID- 7626047
TI  - Purification of an ATP-dependent actin-binding protein from a lower eukaryote,
      Physarum polycephalum.
AB  - A novel protein with a molecular mass of 55 kDa, as determined by SDS-PAGE, was
      purified from plasmodia of Physarum polycephalum. The protein bound to actin
      filaments with a stoichiometry of 0.27 moles per mole of actin with an apparent
      dissociation constant of 4 x 10(-8) M. In the presence of ATP, the protein
      dissociated from actin filaments. Adenosine 5-(gamma-thio)triphosphate and adenyl
      5'-yl imidodiphosphate also abolished the actin-binding activity of the protein,
      but GTP did not. Because the cytoplasmic concentration of ATP oscillates in
      association with the shuttle streaming of the cytoplasm, it is possible that this
      protein might be involved in the actin-linked regulation of cytoplasmic
      streaming.

PMID- 7626048
TI  - Unusual processing of GP280, a protein associated with the intermicrovillar areas
      of yolk sac epithelial cells: plasma membrane delivery of immature protein.
AB  - We have previously shown the close association with endocytosis of 2
      glycoproteins, gp330 and gp280, expressed within the clathrin coated
      intermicrovillar areas of epithelial cells lining the proximal tubule and
      visceral layer of the yolk sac. Exposure at 37 degrees C of yolk sac epithelial
      cells in the presence of antibodies to gp280 induced disruption of the early
      endocytic pathway whereas anti-gp330 antibodies did not. In this study, using
      yolk sac epithelial cells in culture, we show that, in contrast to gp330 which is
      processed by the Golgi enzymes before expression on the plasma membrane, gp280
      follows an unusual processing pathway: indeed, although the bulk of the plasma
      membrane gp280 is endoglycosidase H resistant, the protein is initially targeted
      to the plasma membrane in an endoglycosidase H sensitive form. This implies that
      processing takes place mainly, if not exclusively, by recycling in the Golgi
      apparatus.

PMID- 7626049
TI  - Ginkgo biloba extract (EGb 761) protects human low density lipoproteins against
      oxidative modification mediated by copper.
AB  - The antioxidant effects of Ginkgo biloba extract (EGb 761) on copper-mediated
      human low density lipoprotein (LDL) oxidative modification were evaluated by
      several techniques. Human LDL (0.5 mg/ml) in phosphate buffered saline, pH 7.4,
      was incubated with 10 microM cupric sulfate at 37 degrees C under air for 8 hours
      and 24 hours in the presence of varying concentrations of EGb 761. Increases in
      LDL apoB carbonylation, lipid peroxidation, apoB electrophoretic mobility and LDL
      fluorescence were all inhibited when the incubation mixture contained EGb 761 at
      concentrations less than 100 micrograms/ml. This inhibition was EGb 761
      concentration-dependent. Thus, EGb 761 has powerful antioxidant effects on copper
      mediated LDL oxidative modification.

PMID- 7626050
TI  - Determination of the complete covalent structure of the gamma 2 subunit of bovine
      brain G proteins by mass spectrometry.
AB  - The complete covalent structure of the gamma 2 subunit of bovine brain G proteins
      was determined by peptide mapping using matrix-assisted laser desorption
      ionization and electrospray ionization mass spectrometry and by partial
      sequencing using tandem mass spectrometry. Fragments were identified in
      proteolytic digests corresponding to all predicted internal sequences of gamma 2,
      but not for N- or C-terminal sequences. Fragments consistent with modifications
      of the terminal peptides were observed, however. The presence of these postulated
      modifications was verified by tandem mass spectrometry. These studies define the
      structure of the native protein and provide a basis for comparison to expressed
      proteins.

PMID- 7626051
TI  - Increased apoB100 mRNA in inbred strains of mice by estrogen is caused by
      decreased RNA editing protein mRNA.
AB  - Estrogen administration to rats diminishes all apoproteins and lipoproteins from
      plasma. In contrast, some inbred strains of mice raise their plasma apoB and LDL
      levels by more than 2-fold (Srivastava et al, 1993, Eur. J. Biochem. 216, 527
      538). Further studies with 13 inbred strains of mice given 3 micrograms beta
      estradiol/g body weight/day for 5 consecutive days suggest that some mouse
      strains increased their apoB and LDL levels and some did not. To examine the
      mechanism of influence of genetic factors on apoB regulation, two strains, C57L
      and C57BL, that increased their VLDL- and LDL-cholesterol, and 2 strains, BALB
      and C3H, that did not, were chosen. Estrogen increased plasma apoB levels
      selectively in the strains C57L and C57BL, termed as 'responders,' but did not
      change in BALB and C3H, termed as 'non-responders.' One of the mechanisms for
      increased plasma apoB levels could be through increased production of apoB
      containing particles. This possibility was investigated. ApoB and REPR mRNA were
      quantified by RNase protection assay, and apoB-100 mRNA by apoB mRNA editing
      assay. Hepatic apoB mRNA increased by 30% in 'non-responders,' but decreased by
      20% in the 'responders.' However, apoB-100 mRNA increased relative to apoB-48
      mRNA in all the 4 strains by 50%. The mRNA for RNA editing protein (REPR)
      decreased in all strains, suggesting that apoB-100 mRNA increased as a result of
      decreased apoB mRNA editing activity. These results suggest that:(a) modulation
      of apoB mRNA by estrogen was strain-specific;(b) increased apoB100 mRNA in inbred
      strains of mice were caused by decreased apoB mRNA editing activity; and (c) the
      differences in the plasma apoB levels among 'responder' and 'nonresponder'
      strains of mice occur through mechanisms other than the apoB mRNA editing.

PMID- 7626052
TI  - Immunohistochemical detection of binding of CryIA crystal proteins of Bacillus
      thuringiensis in highly resistant strains of Plutella xylostella (L.) from
      Hawaii.
AB  - We detected binding of insecticidal crystal proteins from Bacillus thuringiensis
      in one susceptible strain and six resistant strains of diamondback moth, Plutella
      xylostella, from Hawaii. Immunohistochemical tests with tissue sections from
      larval midguts showed specific binding of CryIA(a), CryIA(b), and CryIA(c) to
      brush border membranes. CryIE, which is not toxic to P. xylostella, did not bind
      to midgut tissues. Larvae from one of the resistant strains ingested extremely
      high concentrations of a commercial formulation containing the three CryIA
      proteins without suffering midgut cell damage or mortality. This same resistant
      strain had previously been found to have greatly reduced binding of radioactively
      labeled CryIA(c) to vesicles prepared from brush border membranes. The finding
      that binding as detected in immunohistochemical tests was not sufficient for
      toxicity suggests that low levels of binding can occur without harmful effects;
      the tests did not reflect in vivo binding, or post-binding factors contribute to
      resistance. Comparison with resistant strains from Florida and the Philippines,
      which did not bind CryIA(b) in previously reported immunohistochemical tests,
      suggests that more than one mechanism of resistance to B. thuringiensis may occur
      within a single species.

PMID- 7626053
TI  - Ornithine decarboxylase from Leishmania mexicana promastigotes: interaction with
      pyridoxal 5'-phosphate and alpha-difluoromethylornithine.
AB  - The catalytic properties of ornithine decarboxylase (ODC) from Leishmania
      mexicana as well as the interaction with its cofactor pyridoxal 5'-phosphate
      (PLP) and the irreversible inhibitor alpha-difluoromethylornithine (DFMO) have
      been studied using partially purified preparations of the enzyme obtained from
      parasite promastigotes. Leishmania extracts prepared in the presence of
      saturating concentrations of PLP yielded an enzyme considerably more resistant to
      heat inactivation and with a three-fold higher activity than the ODC obtained
      without the addition of cofactor. The complete removal of PLP by treatment with
      hydroxylamine yielded the apoenzyme which shows an absolute requirement for PLP
      to recover its enzymatic activity. The Km values for L-ornithine and PLP were 0.7
      mM and 25 microM, respectively, while Ki for DFMO was 0.2 mM. The restoration of
      ODC activity from apoenzyme and cofactor seems to involve time and temperature
      dependent activation processes. L. mexicana ODC has an apparent molecular mass of
      240 +/- 20 kDa.

PMID- 7626054
TI  - The interactions between nitric oxide and brain nerve terminals as studied by
      electron paramagnetic resonance.
AB  - It has been proposed that nitric oxide (NO) toxicity is due to damage to
      mitochondrial iron-sulfur centers, resulting in inhibition of mitochondrial
      respiration and the appearance of an EPR-detectable (g = 2.04) iron-sulfur
      dinitrosyl complex - Fe(RS)2(NO)2. We show that the addition of nitroprusside (an
      NO and NO+ donor) to rat brain synaptosomes generates large (> 30 microM)
      concentrations of EPR-detectable iron-sulfur-dinitrosyl complexes. However, there
      was no correlation between the size of the g = 2.04 EPR signal and the inhibition
      of synaptosomal respiration. No significant loss of intensity was seen from the
      mitochondrial iron-sulfur protein EPR signals. The results are consistent with
      previous data demonstrating that cytochrome oxidase, not iron-sulfur enzymes, is
      the primary target for NO inhibition of brain cell respiration (Brown, G.C. and
      Cooper, C.E. (1994) FEBS Lett. 356, 295-298).

PMID- 7626055
TI  - Alpha-crystallin-like molecular chaperone against the thermal denaturation of
      lens aldose reductase: the effect of divalent metal ions.
AB  - A chaperone-like activity of bovine lens alpha-crystallin against the thermal
      induced aggregation of bovine lens aldose reductase is reported. While the
      precipitation of aldose reductase at 55 degrees C is prevented by alpha
      crystallin present at a ratio of aldose reductase: alpha-crystallin as low as
      1:0.5 (w:w), the heat-induced inactivation of the enzyme occurs regardless of the
      presence of alpha-crystallin. This would suggest that, irrespective of the
      functional integrity of the target protein, alpha-crystallin interferes only with
      aggregation phenomena, having the potential to preserve the lens transparency.
      Calcium and magnesium ions at mM levels affect the antiaggregation action exerted
      by alpha-crystallin either interfering on the formation or reducing the stability
      of the aldose reductase: alpha-crystallin complex.

PMID- 7626056
TI  - Effects of a potent, non-selective endothelin receptor antagonist, [Thr18, gamma
      MeLeu19]-endothelin-1, on the isolated blood vessels.
AB  - The endothelin (ET) receptor has been classified as the ETA1, ETA2, ETB1 and ETB2
      subtypes. BQ-123 and RES-701-1 are the ETA1 and ETB1 antagonists, respectively,
      whereas BQ-788 is the ETB1/ETB2 antagonist. To find the ETA2 antagonist, the
      effects of [Thr18, gamma-MeLeu19]-ET-1 (TM-ET-1) were examined. In the rabbit
      saphenous vein, contraction induced by ET-1 is due to simultaneous activation of
      the ETA1, ETA2, ETB1 and ETB2 receptors whereas contraction induced by
      sarafotoxin S6c is mediated by the ETB1 and ETB2 receptors. Neither BQ-123 nor
      RES-701-1 inhibited these contractions. TM-ET-1 antagonized the effects of ET-1
      and sarafotoxin S6c. In the vein in which the ETB1/ETB2 receptors were
      desensitized and the ETA1 receptor was inhibited by BQ-123, ET-1 still induced
      contraction. This contraction was inhibited by TM-ET-1. In the rat aorta with
      endothelium, ET-3 induced endothelium-dependent relaxation by activating the
      endothelial ETB1 receptor. TM-ET-1 inhibited the effect of ET-3 without changing
      the relaxation induced by carbachol. In the rat aorta without endothelium, ET-1
      induced contraction by activating the smooth muscle ETA1 receptor. TM-ET-1
      inhibited this contraction. These results suggest that TM-ET-1 is a novel
      antagonist against the ETA2 receptor that also inhibits other types of the ET
      receptors.

PMID- 7626057
TI  - A DNA-binding antitumor antibiotic binds to spectrin.
AB  - Aureolic acid group of antibiotics inhibit transcription by reversible binding to
      DNA in presence of divalent magnesium. We for the first time report binding of
      the one of such antitumor antibiotic, mithramycin (MTR), to the major protein
      component of erythrocyte cytoskeleton, spectrin. A reasonably high apparent
      dissociation constant was estimated to be 1.5 microM. The binding of mithramycin
      in the absence of any divalent cation to the large cytoskeletal protein led to
      quenching in the tryptophan fluorescence of the protein. Stern-Volmer quenching
      of the tryptophan residues by acrylamide revealed conformational change in the
      MTR-bound spectrin. This preliminary study might be useful in understanding other
      possible sites of actions after translocation.

PMID- 7626058
TI  - Spontaneous alterations in the covalent structure of synapsin I during in vitro
      aging.
AB  - Synapsin I purified from bovine brain was incubated for 30 days at pH 7.4 and 37
      degrees C. Samples were taken at various times and assayed for isoaspartate
      content using protein-L-isoaspartyl methyltransferase. During the first 22 days,
      synapsin accumulated isoaspartyl sites at a rate of > or = 6 sites per day per
      100 molecules of synapsin. Concomitant with isoaspartate formation, synapsin
      underwent two other types of modification: a substantial degree of spontaneous
      intermolecular cross-linking via the formation of disulfide bonds, and a second,
      less pronounced, irreversible aggregation. The irreversible aggregation
      apparently results from covalent cross-linking of a non-disulfide nature or
      possibly a strong hydrophobic interaction. Isoaspartate accumulated in both
      aggregated and non-aggregated forms of synapsin during in vitro aging. These
      findings demonstrate that synapsin is capable of significant spontaneous covalent
      alteration under physiological conditions. These modifications may play a role in
      the function of, or limit the lifetime of, synapsin in vivo.

PMID- 7626059
TI  - Metabolism of highly persistent PCB congener, 2,4,5,2',4',5'-hexachlorobiphenyl,
      by human CYP2B6.
AB  - Metabolism of 2,4,5,2',4',5'-hexachlorobiphenyl was studied with cDNA-expressed
      human P450 2B isoform, CYP2B6. 3-Hydroxy-2,4,5,2',4',5'-hexachlorobiphenyl was
      identified as a major metabolite, and the formation activity was compared with
      that of dog CYP2B11 and guinea pig P450GP-1. The activity of 3-hydroxylation was
      comparable with that of P450GP-1, but one-tenth of CYP2B11. These results
      indicate that P450 2B in humans as well as other animal species can metabolize
      2,4,5,2',4',5'-hexachlorobiphenyl, and the reason why this PCB congener remained
      most abundantly in human bodies is discussed.

PMID- 7626061
TI  - Regulation of hamster hepatic microsomal triglyceride transfer protein mRNA
      levels by dietary fats.
AB  - The effect of dietary fat on hepatic microsomal triglyceride transfer
      protein(MTP) large subunit mRNA levels in the hamster was examined. Increasing
      the dietary fat concentration from 11.7 energy % to 46.8 energy % caused a 60%
      increase in hepatic MTP mRNA; this increase was shown to be dose-dependent (r =
      0.688 p = 0.0023). MTP mRNA levels correlated significantly with several plasma
      lipoprotein cholesterol parameters. No significant relationship was observed
      between MTP mRNA and either plasma or VLDL triglyceride. The nature of the
      dietary fatty acids also influenced MTP mRNA levels, with trimyristin and
      tripalmitin enriched diets significantly elevating MTP mRNA relative to diets
      enriched in triolein and trilinolein.

PMID- 7626060
TI  - Differential expression of the L10 ribosomal protein during heart development.
AB  - Neural crest cells originating from the posterior rhombencephalon migrate to the
      cardiac outflow tract and participate in division of the aorta and pulmonary
      trunk. Ablation of this region of premigratory neural crest in the chick embryos
      results in nondivision of the outflow vessels. Subtractive hybridization was used
      to identify messages in the outflow tract of embryos with cardiac neural crest
      cells versus those lacking the cardiac neural crest cells. The chick L10
      ribosomal protein was found to be differentially expressed in the outflow tract
      of embryos with cardiac neural crest. Several conditions have been identified
      that involve differential expression of ribosomal proteins, but this is the first
      report of differential expression in eukaryotic embryonic development.

PMID- 7626062
TI  - Mechanism of farnesol cytotoxicity: further evidence for the role of PKC
      dependent signal transduction in farnesol-induced apoptotic cell death.
AB  - Mechanism of the inhibitory effect of isoprenoid farnesol on cell proliferation
      has been studied in human acute leukemia CEM-C1 cells. Farnesol (20 microM)
      reduced the rate of radioactive label incorporation into cellular diacylglycerol
      (DAG) and phosphocholine, the products of degradation of phosphatidylcholine
      (PC), indicating inhibition of PC-specific phospholipase C after about 1 h of
      incubation. Inhibition of phospholipase D by farnesol at the later incubation
      time (about 2 h) was demonstrated by a decrease in synthesis of PC-derived
      phosphatidylethanol in the presence of ethanol. These effects of farnesol on PC
      degradation and formation of DAG were followed by apoptotic fragmentation of
      cellular DNA and inhibition of cell growth. Exogenous DAG reduced the level of
      DNA fragmentation and cell growth inhibition. Results are consistent with the
      involvement of cellular signal transduction in the mechanism of inhibition of
      cell proliferation by farnesol.

PMID- 7626063
TI  - Secretion of endogenous ouabain from bovine adrenocortical cells: role of the
      zona glomerulosa and zona fasciculata.
AB  - Recent experiments have demonstrated the secretion of a ouabain-like compound
      from primary cultures of bovine adrenocortical cells (1). To determine the
      relative contribution of the outer zones of the adrenal cortex to the secretion
      of endogenous ouabain, we measured the content of this steroid in zona
      glomerulosa and zona fasciculata tissue freshly excised from bovine adrenals and
      in the secretion media of primary cell cultures derived from these zones. The
      tissue content of endogenous ouabain was 5.7-fold higher in the zona glomerulosa
      than in the zona fasciculata. The concentration of endogenous ouabain was 4.1
      fold higher in 24-hour conditioned media from zona glomerulosa than in zona
      fasciculata cultures. Angiotensin II and ACTH stimulated the secretion of
      endogenous ouabain from zona glomerulosa cultures, but had no effect on zona
      fasciculata cultures. These findings suggest that endogenous ouabain is primarily
      synthesized and secreted from the adrenal zona glomerulosa.

PMID- 7626064
TI  - The ATP/ADP binding domains of actin are conserved in nucleosome complexed with
      histone H1 and high mobility group-17 protein.
AB  - Chromatin has been proposed to share a common evolutionary origin and analogous
      mechanisms of action with various structures of cytoskeleton such as actin
      filaments. ATP has been shown to facilitate chromatin remodelling, but the exact
      site of its interaction with chromatin has not been elucidated. The facts, that
      ATP binds specifically to actin and promotes its polymerization, led us to
      characterize the possible domains involved in ATP binding in nucleosome.
      Comparison of the sequences of actin and the protein components of nucleosome
      suggests that H2A may contain an adenosine binding site similar to the adenosine
      motif of actin, H1 and/or H2B phosphate/Ca2+ binding sites corresponding to the
      phosphate 1 motif of actin, HMG17 a phosphate/Ca2+ binding site corresponding to
      the phosphate 2 motif of actin. The ability to bind ATP may be involved in the
      organization of chromatin into inactive solenoid-like structures in vivo.

PMID- 7626065
TI  - Isolation and partial characterization of the insulin binding sites of
      Tetrahymena pyriformis.
AB  - The free-living protozoan, Tetrahymena pyriformis, has been shown to specifically
      bind insulin. Insulin causes alterations in metabolic function and an increase in
      insulin binding capacity (hormonal imprinting) in this organism. Previously, an
      insulin-like material was found in both Tetrahymena cell isolates and in their
      growth media. The purpose of this study was to isolate and partially characterize
      the ciliary membrane binding sites for insulin. The methods employed, DEAE and
      affinity chromatography, were published previously for the mammalian insulin
      receptor. Here we report, not the isolation of a mammalian-like receptor protein,
      but a ciliary membrane protein (62-67 kDa) that is immunologically similar to
      insulin. This insulin-like protein may function as both precursor to a soluble
      form and membrane-bound binding site/receptor as has been suggested for Euplotes
      pheromones and mammalian growth factors such as transforming growth factor a and
      epidermal growth factor.

PMID- 7626066
TI  - Effects of antisense oligonucleotides to the cardiac Na+/Ca2+ exchanger on
      cultured cardiac myocytes.
AB  - Antisense oligodeoxynucleotides based on the sequence of the cardiac Na+/Ca2+
      exchanger were used to study the effects of decreasing expression of this protein
      on Na(+)-dependent Ca2+ uptake activity and on the spontaneous beating rate of
      cultured rat cardiac myocytes. Antisense oligos reduced Na+/Ca2+ exchanger
      activity of myocytes approximately 30-40%, compared to sense-treated or untreated
      controls. Antisense treatment also increased the spontaneous beating rate of
      myocardial cells from an average rate of 40 beats to 69 beats per minute,
      compared to sense-treated or untreated controls. These results indicate that
      reduced expression of the Na+/Ca2+ exchanger significantly alters intracellular
      Ca2+ regulation leading to an enhanced spontaneous beating rate and, presumably,
      a shortened duration of the cardiac cycle in developing myocytes.

PMID- 7626067
TI  - Coupling of a single receptor to two different G proteins in the signal
      transduction of FMRFamide-related peptides.
AB  - A series of studies, which have investigated the membrane receptor-mediated
      signal transduction of PDVDHVFLRFamide in the locust oviduct, suggest the
      presence of a novel ligand-receptor reaction system. In this system, inhibitory
      peptides and stimulatory peptides share a single receptor by having the same
      binding sequence, VFLRFamide, but are able to produce opposite muscle responses
      due to the differences in activation sites. In this research, the results from
      both "guanine nucleotide effect assay" and GTPase assay indicated that the
      receptors for the inhibitory and stimulatory FMRFamide-related peptides (FaRPs)
      are coupled with G proteins and both inhibitory and excitatory effects of FaRPs
      on locust oviduct are through the activation of G proteins. Thus it is very
      likely that the receptor is coupled with two different G proteins. The activation
      of one is responsible for the inhibitory effect and the activation of the other
      is responsible for the stimulatory effect.

PMID- 7626068
TI  - Stereoselective hydrolysis catalyzed by a Bacillus endoglucanase in family D.
AB  - An endoglucanase in family D, purified from a strain of Bacillus, was found to
      catalyze the hydrolysis of p-nitrophenyl beta-D-cellotrioside to generate alpha
      cellobiose, as determined by 1H-NMR spectroscopy. The hydrolysis of the beta-1,4
      glucosidic bond by the enzyme proceeds, therefore, by an inversion mechanism.
      Furthermore, the interconversion of the alpha- and beta-anomeric protons in the
      products of hydrolysis, after equilibrium had been reached by mutarotation, was
      directly characterized by magnetization transfer NMR experiment that exploited
      the truncated driven nuclear Overhauser effect.

PMID- 7626069
TI  - Effect of altered redox states on expression and DNA-binding activity of hypoxia
      inducible factor 1.
AB  - Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric basic helix-loop-helix
      (bHLH)-PAS DNA-binding protein tightly regulated by cellular oxygen tension.
      Cellular redox states are related to hypoxia by changes in the expression of
      redox regulated genes and the generation of reactive oxygen intermediates. Here,
      we provide evidence that alteration of cellular redox states by treating cells
      with H2O2 or dithiothreitol impairs hypoxia signaling mechanisms and the
      expression of HIF-1 alpha protein in hypoxic cells. In addition, HIF-1 DNA
      binding activity in vitro is sensitive to oxidizing reagents diamide and H2O2 and
      the alkylating agent N-ethylmaleimide. The activity of N-ethylmaleimide
      inactivated HIF-1 can be partially restored by addition of nuclear extract from
      nonhypoxic cells.

PMID- 7626070
TI  - Ferric nitrilotriacetate (Fe-NTA) is a potent hepatic tumor promoter and acts
      through the generation of oxidative stress.
AB  - Fe-NTA is a known renal carcinogen. However, little is known about its
      carcinogenic potential in liver. In this study we for the first time show that Fe
      NTA is a potent hepatic tumor promoter. Fe-NTA administration induced dose
      dependently the hepatic ornithine decarboxylase (ODC) activity several folds as
      compared to its activity in the saline-treated rats. Similarly, hepatic DNA
      synthesis which is measured as [3H]thymidine incorporation in DNA is also
      increased following Fe-NTA treatment. The effects of Fe-NTA were similar to other
      tumor promoters not only with respect to inducing ODC activity and [3H]thymidine
      incorporation in DNA but also in depleting antioxidant armory of the tissue. Fe
      NTA depleted levels of glutathione to about 35% of the saline-treated control and
      activities of antioxidant enzymes catalase, glutathione peroxidase, glutathione
      reductase and glucose 6-phosphate dehydrogenase decreased significantly (45-55%
      of saline-treated control). Concomitant with the depletion in antioxidant armory,
      Fe-NTA augmented hepatic microsomal lipid peroxidation more than three folds. The
      pretreatment of rats with antioxidants BHA or BHT diminished the observed effects
      of Fe-NTA. Our data indicate that Fe-NTA is a potent hepatic tumor promoter and
      acts through a mechanism involving oxidative stress.

PMID- 7626071
TI  - A novel missense mutation (C522Y) is present in the beta-hexosaminidase beta
      subunit gene of a Japanese patient with infantile Sandhoff disease.
AB  - A novel missense mutation (1565G-->A) was identified in the cDNA and genomic DNA
      coding for the beta-hexosaminidase beta-subunit of a Japanese patient with
      infantile Sandhoff disease. The patient was homozygous for this mutation, which
      should result in a cysteine-to-tyrosine substitution at codon 522. Computer
      assisted analysis of this amino acid substitution predicted alteration in the
      secondary structure in the region of a highly conserved sequence. An
      immunofluorescence study revealed the accumulation of GM2 ganglioside in cultured
      fibroblasts from the patient with this mutation.

PMID- 7626073
TI  - Differential activation of bovine brain N-myristoyltransferase(s) by a cytosolic
      activator.
AB  - N-Myristoyltransferase (NMT) is an essential eukaryotic enzyme that catalyses the
      transfer of myristate from myristoyl-CoA to the NH2-terminal glycine residue of a
      number of important proteins of diverse function. Little is known about the
      control and regulation of NMT in higher eukaryotes. We have identified a N
      myristoyltransferase activator (NAF45) which copurified with one form of bovine
      brain NMT activity which failed to bind to phosphocellulose column chromatography
      (NMT.PU) and represented 32 +/- 4% of the total NMT activity applied to this
      column. The NAF45 and NMT activities were resolved by mono Q column
      chromatography from the NMT.PU fraction. Resolution resulted in a loss of NMT.PU
      activity. NAF45 was a nondialysable molecule with an apparent molecular mass of
      45 kDa. Reconstitution of the NAF45 and NMT resulted in the recovery of NMT
      activity, indicating that this form of NMT is dependent on the presence of NAF45.
      NAF45 was able to stimulate other forms of NMT activity (maximum of 3-4 fold) in
      a highly cooperative fashion (Hills coefficient of approximately 5.5).
      Stimulation was in terms of both the rate of myristoylation and the overall
      production of myristoylpeptide, indicating that the end point of the reaction was
      shifted in favour of myristoylpeptide production. NAF45 was able to compete with
      NIP71 for NMT [King, M.J. and Sharma, R.K. (1993) Biochem, J. 291, 635-639],
      although its affinity appeared lower than the NIP71.

PMID- 7626072
TI  - Adrenomedullin decreases both cytosolic Ca2+ concentration and Ca(2+)-sensitivity
      in pig coronary arterial smooth muscle.
AB  - Adrenomedullin (AM) is a newly identified vasorelaxant peptide which circulates
      in human plasma. We investigated the cellular mechanisms of AM-induced relaxation
      in the pig coronary artery, using fura-2 fluorometry and receptor-coupled
      membrane permeabilization by alpha-toxin. AM inhibited both the elevations of
      cytosolic Ca2+ concentration ([Ca2+]i) and the tension induced by high K(+)
      depolarization and by U46619. The extent of the tension inhibition was much
      greater than expected based on the extent of reductions of [Ca2+]i. Thus, the
      [Ca2+]i (abscissa)-tension (ordinate) relation shifted to the right by AM. In
      alpha-toxin-permeabilized strips, AM decreased the tension development at
      constant [Ca2+]i (pCA 6.5) in the presence of GTP, whereas GDP beta S antagonized
      this effect. We thus conclude that AM relaxes the coronary artery not only by
      decreasing [Ca2]i but also by decreasing the Ca(2+)-sensitivity of the
      contractile apparatus, as mediated by G-protein.

PMID- 7626074
TI  - Inhibition of diamine oxidase activity by metronidazole.
AB  - Metronidazole was found to be a non-competitive inhibitor of man, rabbit and rat
      intestinal diamine oxidases with an inhibition constant value of approximately
      10(-4) M. The purified bovine serum amine oxidase was not inhibited, whereas the
      purified swine kidney enzyme gave similar results. These findings suggest that
      metronidazole and similar compounds, used as antibacterial and antiprotozoal
      drugs, should be given under careful control, especially when administered for
      long times, because a decrease of intestinal diamine oxidase activity was proven
      to be a risk factor for several pathologies of this organ.

PMID- 7626075
TI  - Cloning of a new FRTL5-derived cell line stably expressing active human thyroid
      peroxidase.
AB  - A full-length cDNA clone for human thyroid peroxidase inserted into the mammalian
      cell expression vector pECE was stably transfected into the rat thyroid cell line
      FRTL5. Clones expressed immunologically and enzymatically assessed human thyroid
      peroxidase protein. Methimazole (25 microM) inhibited the thyroid peroxidase
      activity dose-dependently and this effect was completely antagonised by 100
      microM NaI. Ethylenethiourea, metabolite of dithiocarbamate pesticides, inhibited
      the enzyme at 50 microM. Thus, we have obtained thyroidal cells stably expressing
      enzymatically active human thyroid peroxidase which can be pharmacologically
      modulated and studied.

PMID- 7626076
TI  - Regulation of heme oxygenase mRNA in mesangial cells: prostaglandin E2 negatively
      modulates interleukin-1-induced heme oxygenase-1 mRNA.
AB  - Heme oxygenase (EC 1.14.99.3) is the rate-limiting enzyme in heme catabolism.
      Several lines of evidence suggest a possible role for heme oxygenase in the
      inflammatory process and in cellular signaling. We have evaluated the regulation
      of heme oxygenase-1 mRNA induction by the inflammatory stimuli, phorbol 12,13
      myristate acetate, heat shock and interleukin-1 beta in cultured rat mesangial
      cells. Phorbol 12,13-myristate acetate and heat shock rapidly (maximal at 2-3
      hrs) induced heme oxygenase-1 mRNA. The effect of interleukin-1 beta on heme
      oxygenase-1 mRNA induction was slower (maximal at 12 hrs) and modest. However, in
      the presence of a cyclooxygenase inhibitor, indomethacin, interleukin-1 beta
      strongly induced heme oxygenase-1 mRNA. The addition of exogenous PGE2 reversed
      the effect of indomethacin. These data suggest that pro-inflammatory stimuli
      increase heme oxygenase-1 mRNA expression in rat mesangial cells and that
      interleukin-1 beta-induced heme oxygenase-1 mRNA level is negatively modulated by
      PGE2.

PMID- 7626077
TI  - Sex steroids up-regulate E-cadherin expression in hormone-responsive LNCaP human
      prostate cancer cells.
AB  - There is convincing evidence that a reduced expression of the E-cadherin cell
      cell adhesion molecule associates with low tumor grade and poor prognosis in
      prostate cancer patients. However, little is known on how E-cadherin levels are
      regulated in human prostate cancer cells. We have inspected the effect of both
      androgens and estrogen on the expression of E-cadherin in the hormone-responsive
      LNCaP prostate tumor cell line, which is endowed with both androgen and estrogen
      receptors. Using both Dot Blot analysis and immunocytochemistry we have observed
      that either steroid significantly increased E-cadherin levels in these cells;
      this effect was not reversed by the simultaneous addition of the relevant
      antagonist, hydroxyflutamide or ICI-182,780.

PMID- 7626078
TI  - Loss of heterozygosity in chromosomes 1, 5, 7 and 13 in mouse hepatoma detected
      by systematic genome-wide scanning using RLGS genetic map.
AB  - We have developed an RLGS-based scanning system to detect DNA alteration in tumor
      tissues, using 575 mapped spots/loci in a single gel. This system is very
      powerful for screening and identifying not only loss of heterozygosity (LOH) but
      also DNA methylation change. In this study, we applied this system to search for
      the LOH of hepatoma from an interspecific F1 hybrid between Mus spretus and
      C57BL/6 with SV40 early T antigen transgene connected to a mouse major urinary
      protein enhancer/promoter. Comparing the RLGS profiles of each tumor to that of
      the normal tissue showed significant LOH in chromosomes 1, 5, 7 and 13.

PMID- 7626079
TI  - Cloning and characterisation of a bovine P2Y receptor.
AB  - Using a chick P2Y1 receptor cDNA probe we have isolated a mammalian P2Y receptor
      clone from a bovine aortic endothelial cell library. The sequence has a high
      degree of similarity to the chick P2Y1 clone. When transfected into the Jurkat
      cell line, the cDNA conferred sensitivity to purinoceptor agonists. Using fura-2
      loaded cells the potency order at the receptor was found to be 2
      methylthioadenosine 5' triphosphate = adenosine 5' diphosphate > adenosine 5'
      triphosphate >> alpha,beta-methyleneadenosine 5' triphosphate and uridine 5'
      triphosphate. This corresponds to the agonist potency order expected for the
      bovine aortic endothelial cell P2Y receptor.

PMID- 7626080
TI  - Heterologous multimeric assembly is essential for K+ channel activity of neuronal
      and cardiac G-protein-activated inward rectifiers.
AB  - The family of G-protein-activated inward-rectifiers K+ channels presently
      comprise at least 3 cloned members called GIRK1, GIRK2 and GIRK3. A close
      structural parent of GIRK channels has recently been described as being an ATP
      sensitive K+ channel. This paper shows that Xenopus expression of this new
      channel that we call GIRK4 does not produce an ATP-inhibitable activity with a
      pharmacological activation by pinacidil as previously described but instead a G
      protein activated inward-rectifier. While oocyte expression of single subunits is
      infrequent and relatively modest in intensity, expression of GIRK1,2, GIRK1,4 and
      GIRK2,4 mixtures leads to routine and robust expression of K+ channels indicating
      that heterologous subunit assembly is necessary for activity. Activity of
      GIRK1,2, GIRK1,4 and GIRK2,4 channels required the presence of ATP acting as an
      activator at the cytoplasmic face and is further activated by the beta gamma
      subunits.

PMID- 7626081
TI  - Redistribution of protein kinase C isoforms in human neutrophils stimulated by
      formyl peptides and phorbol myristate acetate.
AB  - The redistribution of protein kinase C (PKC) isoforms between the cytosolic and
      plasma membrane fractions of stimulated human polymorphonuclear leukocytes (PMN)
      was analysed by means of western blotting with antibodies against PKC beta I,
      beta II and Zeta. Treatment of PMN with 1 microM formyl-methionyl-leucyl
      phenylalanine (fMLP) induced a rapid (5-10 sec) and sustained (at least 10 min)
      increase in the membrane association of PKC beta I, beta II, and the two
      immunoreactive proteins (76-81 kDa) recognized by the antibody directed against
      PKC zeta. Optimal translocation of PKC isoforms to the plasma membrane occurred
      in the presence of 10(-6) M fMLP and was not associated with a detectable fall in
      cytosolic PKC. In the absence of external calcium, the translocation of all PKC
      isoforms induced by fMLP was rapid (5 sec) but the membrane association of PKC
      was lost within one minute. Unlike fMLP, phorbol myristate acetate (PMA) induced
      a concentration-dependent translocation of the PKC isoforms, which persisted in
      the membrane in the absence of external calcium. These data provide the first
      evidence of redistribution of PKC isoforms by a chemoattractant. They further
      indicate that external calcium plays a crucial role in the persistence of the
      membrane association of PKC beta I, beta II and zeta induced by formyl peptides.

PMID- 7626082
TI  - The amino-terminal fragment of the adenylate cyclase activating polypeptide
      (PACAP) receptor functions as a high affinity PACAP binding domain.
AB  - The PACAP receptor represents a member of a novel subfamily of G-protein coupled
      receptors with a common structurally conserved extracellular domain of about 150
      amino acids. We have addressed the question whether this extracellular amino
      terminus of the PACAP type I receptor can solely function as a PACAP binding
      domain. For that purpose a cDNA was constructed that encodes the membrane
      anchored amino-terminus of the rat PACAP receptor including the decapeptide
      epitope EQKLISEEDL for immunodetection. COS-7 cells were transfected with this
      cDNA and a comparable construct of the wild-type receptor. Binding analysis
      showed that the amino-terminal fragment of the PACAP receptor bound PACAP with
      high-affinity (Kd = 3.8 nM; Bmax = 12.8 pmol/mg protein). In comparison to the
      full-length receptor (Kd = 0.2 nM; Bmax = 1.96 pmol/mg protein) its affinity was
      reduced by a factor of about 20. The results suggest that the amino-terminus of
      the PACAP receptor functions as the major binding site for its ligand.

PMID- 7626083
TI  - Significance of Phe-220 and Gln-221 in the catalytic mechanism of farnesyl
      diphosphate synthase of Bacillus stearothermophilus.
AB  - Farnesyl diphosphate synthase [EC 2.5.1.10] from Bacillus stearothermophilus was
      specifically altered at two amino acid residues by using site-directed
      mutagenesis. The highly conserved Phe and Gln residues at the sequential amino
      acid positions 220-221 in an upstream part of the putative substrate binding site
      were replaced with Ala and Glu, respectively. These mutageneses (F220A and Q221E)
      resulted in 10(-5) and 10(-3) decreases in catalytic activity of farnesyl
      diphosphate synthesis, respectively. Michaelis constants of the Q221E mutant for
      the allylic substrates (dimethylallyl- and geranyl diphosphates) increased
      approximately 25- and 2-folds, respectively, compared to wild type, whereas those
      for the homoallylic substrate (isopentenyl diphosphate) were not altered much.
      These results suggest that the Phe-Gln motif is involved not only in the binding
      of allylic substrates but also in the catalysis by farnesyl diphosphate synthase.

PMID- 7626084
TI  - Effect of CCK-B/gastrin receptor antagonist on pepsinogen-producing cells during
      omeprazole treatment.

PMID- 7626085
TI  - Decreased MAP kinase activity in human gastric adenocarcinoma.
AB  - We investigated the cellular signaling events involved in gastric cancer by
      examining the role of mitogen activated protein kinase (MAPK) in normal and
      transformed human gastric tissue. A significant loss in both MAPK abundance and
      activity was found in the membrane fractions of the adenocarcinomas when compared
      to the histologically normal gastric tissue, while no significant alteration in
      MAPK was seen in the cytosolic fractions from these two tissue types. These
      findings suggest that reduction in MAPK abundance and activity are associated
      with loss of normal growth control in human gastric adenocarcinoma.

PMID- 7626086
TI  - Inhibition of rabbit reticulocyte guanine nucleotide exchange factor activity by
      heparin and its reversal by polyamines.
AB  - We have previously demonstrated that phosphorylation of the 82-kDa subunit of the
      guanine nucleotide exchange factor, eIF-2B, by casein kinases I and II stimulates
      eIF-2B activity. In the present report, we show that heparin binds to eIF-2B (KD
      approximately 0.3 microM) and inhibits the GDP/GTP exchange activity of eIF-2B.
      The effect is dose dependent, with half-maximal inhibition (IC50) achieved at
      0.03 microM heparin. Although spermidine alone does not stimulate or inhibit
      guanine nucleotide exchange, it reverses the inhibitory effect of heparin up to
      90 percent (IC50 = 0.22 mM). ATP and NADPH which interact with the 65 and 55-kDa
      subunits also partially relieve heparin inhibition of nucleotide exchange, and
      the effects of ATP and NADPH are additive. By using a gel overlay technique, we
      demonstrate that 125I-heparin binds to the 82, 65 and 55-kDa subunits of eIF-2B.

PMID- 7626087
TI  - The alternatively spliced type II corticotropin-releasing factor receptor, stably
      expressed in LLCPK-1 cells, is not well coupled to the G protein(s).
AB  - Two alternatively spliced corticotropin-releasing factor receptor (CRF-R) cDNAs,
      type I and type II, were recently isolated from a human cDNA library. The two
      cDNAs are identical except that the type II cDNA encodes an additional 29 amino
      acid inserted in the first putative cytoplasmic loop. Since the first cytoplasmic
      loop is highly conserved in all the members of the hCRF receptor family we have
      examined whether the presence of the 29 amino acid cassette in CRF-RII influences
      G protein coupling in LLCPK-1 cells stably expressing the type I and type II hCRF
      receptors. Whether measured in intact cells or in membrane preparations, LLCPK-1
      cells stably expressing CRF-RII have a 4-5 fold lower binding affinity. Maximal
      CRF-stimulated cAMP accumulation in LLCPK-1 cells stably expressing CRF-RI was 10
      15-fold higher than that in LLCPK-1 cells expressing CRF-RII. The EC50 for CRF
      stimulated cAMP accumulation in hCRF-RI-expressing cells was in the range of 0.5
      +/- 0.2 nM. In contrast, the EC50 for CRF-stimulated cAMP accumulation in hCRF
      RII expressing cells was 7.7 +/- 0.2 nM. hCRF increased phosphoinositide turnover
      in LLCPK-1 cells stably expressing CRF-RI but not in those expressing CRF-RII;
      this effect required hCRF concentrations of 100 nM and higher. In membrane
      preparations, GTP-gamma-S inhibited hCRF binding to CRF-RI and shifted the
      binding Kd from 4.5 nM to 16.7 nM. Conversely, GTP-gamma-S did not influence hCRF
      binding to CRF-RII in broken cell membranes. Additionally, CRF-stimulated
      adenylate cyclase activity in cell membranes expressing CRF-RI was potentiated by
      GTP, whereas CRF-stimulated adenylate cyclase activity in cell membranes
      expressing CRF-RII was insensitive to GTP. These data indicate that CRF-RII is
      not well coupled to the G protein. Since the only difference between the CRF-RII
      and CRF-RI is the insert in the first putative cytoplasmic loop, these data
      indicate that the first cytoplasmic loop plays a crucial role in hCRF receptor
      coupling to the G protein.

PMID- 7626088
TI  - G beta gamma directly binds to the carboxyl terminus of the G protein-gated
      muscarinic K+ channel, GIRK1.
AB  - beta gamma Subunits of heterotrimeric GTP-binding proteins (G beta gamma)
      activate the inwardly rectifying muscarinic K+ channel, GIRK1. The significant
      role for the carboxyl (C) terminus of GIRK1 in this interaction has been
      suggested. However, it is still unknown whether G beta gamma directly interacts
      with GIRK1. To elucidate the molecular basis of G beta gamma-activation of GIRK1,
      we examined the binding properties of G beta gamma to the C terminus of GIRK1
      cloned from mouse brain cDNA library (MB-GIRK1). The C terminus of MB-GIRK1 fused
      with glutathione S-transferase directly bound to purified G beta gamma.
      Incubation of the C terminus with Gi pretreated with GTP gamma S, but not with
      GDP, resulted in the binding of Gi beta gamma to the protein. Purified G alpha
      GDP, but not G alpha-GTP gamma S, inhibited the binding of G beta gamma to the
      fusion protein. These results indicate that G beta gamma dissociated from G alpha
      may directly bind to the C terminus of GIRK1.

PMID- 7626090
TI  - Structural characterization of thymidine phosphorylase purified from human
      placenta.
AB  - Human thymidine phosphorylase (dThdPase) is thought to be identical to an
      angiogenesis factor, platelet-derived endothelial cell growth factor (PD-ECGF).
      However, the whole amino acid sequence of dThdPase is still unknown. N-terminal
      amino acid sequencing of dThdPase isolated from human placenta gave the sequence
      Ac-AALMTPGTGAPPAPG. Comparison with the sequence predicted from the PD-ECGF cDNA
      reveals that residues 2-16 of dThdPase are identical to that of PD-ECGF. If
      dThdPase and PD-ECGF are derived from the same gene, the primary translational
      product of dThdPase would be processed one amino acid from the translation
      initiating methionine residue and Ala-2 acetylated. Since placental and platelet
      PD-ECGF is reported to be processed at Thr-6 and Ala-11, respectively, and the N
      terminal end is not blocked, further study is needed to clarify the reason for
      this discrepancy and whether the difference in N-terminal sequence affects the
      physiological function of these molecules.

PMID- 7626089
TI  - Antibodies to Schistosoma japonicum (Asian bloodfluke) paramyosin induced by
      nucleic acid vaccination.
AB  - Nucleic acid vaccination by intramuscular or intradermal delivery of DNA plasmids
      encoding antigenic proteins has been shown to confer protection in experimental
      animals against viruses and unicellular protozoan parasites. However, this
      revolutionary approach has not been tested for induction of immunity to
      multicellular parasites, such as trematode worms. We report here, for the first
      time, that murine antibodies can be induced by intramuscular injection with
      plasmid DNA encoding fragments of Schistosoma japonicum paramyosin (Sj97), a 97
      kDa molecule and a promising vaccine candidate in schistosomiasis. An additional
      construct containing the gene encoding full-length glutathione S-transferase
      (Sj26), another recognised anti-schistosome vaccine target, failed to raise
      detectable levels of specific antibody.

PMID- 7626091
TI  - Single amino acid residue-linked signaling shifts in the transduction activities
      of atrial and type C natriuretic factor receptor guanylate cyclases.
AB  - The type A (ANF) and the type C (CNP) natriuretic factor-activated guanylate
      cyclases, respectively termed as ANF-RGC and CNP-RGC, are single-chain
      transmembrane-spanning proteins, containing ligand binding and catalytic cyclase
      domains at two opposite ends of the protein. The binding activity resides at the
      N-terminal extracellular region and the catalytic cyclase activity at the
      carboxyl end. The ANF-RGC residue Leu-364, residing in the extracellular region,
      is critical for the ANF-binding activity; the CNP-RGC residue Glu-332 is critical
      for the CNP-binding activity. The counter part of CNP-RGC-Glu-332 residue is the
      ANF-RGC residue Gln-338 and of ANF-RGC-Leu-364 residue in CNP-RGC is the Valine
      358. The present study shows a remarkable signal switching phenomenon associated
      with these residues. By changing the ANF-RGC residue Gln-338 to Glu, ANF-RGC
      switches from no to significant CNP signal transduction activity; similarly, a
      change from Valine-358 to Leu generates ANF signal transduction activity in CNP
      RGC. These acquired signal transduction activities in the cyclases are in
      addition to their natural signal transduction activities. Thus, these new
      cyclases show both ANF and CNP signaling activities.

PMID- 7626092
TI  - Cytochrome c oxidase catalysis of the reduction of nitric oxide to nitrous oxide.
AB  - Reduction of nitric oxide (NO) to nitrous oxide (N2O) is catalyzed by bovine
      heart cytochrome c oxidase (CcO) in anaerobic solutions at pH 7.2 and 20 degrees
      C. Cyanide inhibits and forms Fea3(3+)CN. The mononitrosyl (Fea3(2+)NO), but not
      the dinitrosyl (Fea3(2+)NO; CuB+NO), is a likely intermediate in N2O formation.
      One-electron reduction of NO at Fea3(2+) could yield N2O via HNO. However, a two
      electron reduction of the NO ligand to give an intermediate that reacts with a
      second NO to give N2O and H2O appears more likely. Conversion of NO to N2O is
      favored by low levels of both NO and O2, higher NO levels can inhibit both
      cytochrome c oxidase and NO reductase activities. Raising the O2 level will favor
      catalysis of NO oxidation to NO2 by CcO. The reactions of NO and the specific CcO
      activity that occur in tissue will be critically dependent on NO, O2, and CcO
      levels.

PMID- 7626093
TI  - Inhibition of PDGF-induced phospholipase D but not phospholipase C activation by
      herbimycin A.
AB  - It is known that PDGF-induced phospholipase D (PLD) activation occurs downstream
      of phospholipase C gamma 1 (PLC-gamma 1) activation. Herbimycin A, a specific
      inhibitor of Src family tyrosine kinase, dose-dependently inhibited PDGF-induced
      PLD activation (IC50 of 8 micrograms/ml) without affecting PLC-gamma 1 activation
      and significantly reduced PDGF-induced tyrosine phosphorylations of 40-46 kD and
      60 kD proteins in PLC-gamma 1-overexpressing NIH 3T3 gamma 1 cells. These results
      suggest that PLC activation is necessary but not sufficient for PDGF-induced PLD
      activation. Tyrosine phosphorylation of p40-p46 and p60 is thought to be involved
      in PDGF-induced activation of PLD but not of PLC.

PMID- 7626094
TI  - 4-Hydroxy-2-nonenal-trapping ELISA: direct evidence for the release of a
      cytotoxic aldehyde from oxidized low density lipoproteins.
AB  - Among the aldehydes that originate from the peroxidation of cellular membrane
      lipids, 4-hydroxy-2-nonenal (HNE) is thought to be largely responsible for
      cytopathological effects observed during oxidative stress. Taking advantage of
      the fact that HNE is very reactive with proteins and forms stable Michael
      addition-type adducts, a novel immunochemical procedure for quantifying "free"
      HNE has been developed. The method designated as "HNE-trapping ELISA" is based on
      the detection of HNE trapped by a protein that has been coated in the
      immunoplate. The HNE-derived epitopes generated in the coating protein are then
      detected by the ELISA using a monoclonal antibody (mAbHNEJ-2) specific to the
      haptenic groups of the HNE-protein conjugates. Using this method, we determined
      that a considerable amount of HNE was released from human plasma low density
      lipoproteins (LDL) treated with copper ions or endothelial cells.

PMID- 7626095
TI  - Allosteric regulation of eukaryotic initiation factor eIF-2B by adenine
      nucleotides.
AB  - Previous studies have shown that eIF-2B purified from rabbit reticulocytes binds
      ATP and that the binding is prevented by NADP+. Because NADP+ inhibits the
      activity of eIF-2B in in vitro reactions we have examined whether or not the
      activity of eIF-2B is modulated by ATP. In these studies, eIF-2B, purified from
      rat liver, was incubated with ATP prior to assay. We found that the activity of
      eIF-2B was inhibited with an IC50 of approximately 0.8 mM. The inhibition was not
      due to phosphorylation of the factor. However, the inhibition of eIF-2B activity
      caused by ATP could be prevented by coincubation with either NADPH or fructose
      1,6-bisphosphate. The activity of eIF-2B was also inhibited following addition of
      either ATP or AMPPNP to a post-mitochondrial supernatant prepared from rat liver.
      Therefore, it is possible that the activity of eIF-2B might be allosterically
      regulated in vivo not only by changes in the redox state of pyridine
      dinucleotides but also by changes in the relative amounts of NADPH and ATP.

PMID- 7626096
TI  - Heteroduplex analysis of the Xenopus RNA polymerase I terminator.
AB  - Recent results showed that the Xenopus ribosomal terminator, a conserved 9-bp
      element ("T2/T3 box"), is a pause signal for the RNA polymerase I-elongation
      complex (Labhart, P. [1995] Nucleic Acids Res. 23, 2252-2258). Since the
      terminator is known to function only in one orientation, it was of interest to
      investigate whether the 9-bp pause element had to be present in both DNA-strands
      to mediate termination of RNA polymerase I-transcription. The present
      heteroduplex analysis of the terminator shows that only the double-stranded 9-bp
      element constitutes a functional terminator. Any single-stranded mutation had the
      same down-effect as the corresponding double-stranded (homoduplex) mutation.
      Models for termination by Xenopus RNA polymerase I that are supported or
      eliminated by the present results are discussed.

PMID- 7626097
TI  - Purification and preliminary characterization of three c-type cytochromes from
      Pseudomonas nautica strain 617.
AB  - Three c-type cytochromes, namely cytochrome c553, cytochrome c553(548) and
      cytochrome c', were purified from the marine denitrifying bacterium Pseudomonas
      nautica strain 617. These three monohemic cytochromes present in small amounts
      were preliminarily characterized by physiochemical and spectroscopic techniques.
      The visible and the 1H-NMR spectra show that cytochrome c553 and cytochrome
      c553(548) have histidine-methionine as iron axial ligands. Cytochrome c553 and
      cytochrome c553(548) have mid-point redox potentials of +269 mV and +223 mV, at
      pH 7.6, and their molecular masses are 14 kDa and 17 kDa, respectively.
      Cytochrome c' has a molecular mass of 21 kDa and its visible spectrum is typical
      of a high spin heme.

PMID- 7626098
TI  - The possible involvement of replication-related proteins with a DEAD-box-like
      motif in cell-free DNA replication of Xenopus eggs.
AB  - Two types of antibodies were prepared: one directed against an oligopeptide
      specific to P1 protein, a mammalian homologue of yeast MCM3, and the other
      against an oligopeptide with a DEAD box motif, which is a highly conserved
      sequence in the P1 protein family. Immunoprecipitation of the eluate from anti-P1
      family IgG-bound beads, which had been incubated in Xenopus egg extracts, with
      anti-P1 IgG-bound beads revealed that three proteins were coprecipitated. Two
      proteins remained in the supernatant after the immunoprecipitation of the eluate
      from anti-P1 family IgG-bound beads with anti-P1 IgG-bound beads. The
      immunodepleted extracts with anti-P1 family IgG-bound beads showed much lower DNA
      replication activity than did mock-treated extracts. Recovery of replication was
      achieved by supplementing the depleted extracts with both the eluate from anti-P1
      IgG-bound beads and the supernatant obtained after the immunoprecipitation of the
      eluate with anti-P1 IgG-bound beads but not by supplementing the extracts with
      only the proteins eluted from anti-P1 IgG-bound beads. These findings suggest
      that some proteins containing a DEAD-box-like motif as well as mammalian
      homologues of yeast MCM2, MCM3 and CDC46 play an important role in cell-free DNA
      replication of Xenopus eggs.

PMID- 7626099
TI  - Escherichia coli K-12 copper-containing monoamine oxidase: investigation of the
      copper binding ligands by site-directed mutagenesis, elemental analysis and topa
      quinone formation.
AB  - Copper-containing monoamine oxidase (EC 1.4.3.6) from Escherichia coli is a
      periplasmic enzyme containing topa quinone in addition to divalent copper as a
      cofactor. The amino acid sequence of E. coli monoamine oxidase was compared to
      several cloned amine oxidase genes and five well-conserved histidine residues
      were found. Site-directed mutagenesis studies were performed to determine which
      histidine residue serves as the binding ligand to the copper. Enzyme activity,
      absorption spectrum, and atomic absorption spectrophotometry of the mutant
      enzymes indicated that histidines 470, 554, and 556 are the copper binding
      ligands. The absorption spectra of phenylhydrazine derivatives suggested that
      copper is necessary for topa quinone formation.

PMID- 7626100
TI  - A hypothetical structural role for proline residues in the flanking segments of
      protein-protein interaction sites.
AB  - An examination of more than 1600 protein-protein interaction sites indicated that
      proline is the residue most commonly found near interaction sites. A structural
      role is distinguished for these proline residues in the flanking segments of
      protein-protein interaction sites. The unique nature of proline helps protect the
      integrity and present the sites, thus promoting protein-protein interactions. A
      novel approach to the design and development of potent peptide drugs and a simple
      predictive method to identify protein-protein interaction sites directly from the
      amino acid sequence have been developed based on this finding. The recognition of
      this structural role for proline has strong implications for protein chemistry
      and protein engineering.

PMID- 7626101
TI  - Prostaglandin F2 alpha inhibits epidermal growth factor binding to cellular
      receptors on adipocyte precursors in primary culture.
AB  - Prostaglandin F2 alpha (PGF2 alpha) and epidermal growth factor (EGF) are potent
      differentiation inhibitors of adipocyte precursors in primary culture. We show
      here that PGF2 alpha specifically inhibited EGF binding to adipocyte precursors
      in a dose dependent fashion. Scatchard analysis indicates that PGF2 alpha causes
      a 50% decrease in the number of available EGF cell surface receptors without
      change in receptor affinity. Comparison of EGF binding at different temperatures
      and on fixed cells indicates that PGF2 alpha increases internalization of EGF
      receptor complexes in adipocyte precursors. Phorbol myristate acetate (PMA) also
      inhibited EGF binding in adipocyte precursors. PGF2 alpha effect was abolished in
      cells exposed to prolonged treatment with PMA indicating that PGF2 alpha effect
      on EGF binding is mediated by protein kinase C. These results would suggest that
      in adipocyte precursors PGF2 alpha may be the physiological mediator of phorbol
      ester effect on EGF receptor properties.

PMID- 7626102
TI  - Roles of alpha 1-adrenoceptor activity in the release of nitric oxide during
      ischemia of the canine heart.
AB  - The difference in end-products of the nitric oxide, i.e., nitrate-plus-nitrite,
      in the coronary arterial and venous blood was increased during coronary
      hypoperfusion of the canine heart (12.8 +/- 0.6 vs. 2.2 +/- 0.2 microM at the
      baseline). Norepinephrine from sympathetic nerve endings in the heart is released
      due to ischemic stress, however the relation of norepinephrine with nitric oxide
      is unknown during ischemia. Neither beta- or alpha 2-adrenoceptor antagonists
      attenuated the release of nitric oxide during coronary hypoperfusion. An
      intracoronary infusion of an alpha 1-adrenoceptor antagonist attenuated the
      release of nitric oxide during coronary hypoperfusion (5.3 +/- 0.4 microM), and
      the attenuation of alpha 1-adrenoceptor activity further decreased coronary blood
      flow during hypoperfusion. These findings suggest that alpha 1-adrenoceptor
      activity contributes to the mechanisms whereby nitric oxide is released from the
      ischemic myocardium.

PMID- 7626104
TI  - Rapid reaction of singlet molecular oxygen (1O2) with p-aminobenzoic acid (PABA)
      in aqueous solution.
AB  - The reaction of singlet molecular oxygen (1O2) with p-aminobenzoic acid (PABA) is
      quite rapid. The rate constant for reaction of 1O2 with PABA was measured in
      buffered aqueous solution by the method of competition kinetics and found to be
      8.9 x 10(8) M-1 sec-1. The results of a Stern-Volmer analysis indicate that
      additional loss of 1O2 does not occur through physical quenching by PABA.
      Although illuminated PABA solutions are known to form 1O2, it appears that PABA
      is also a very efficient sink for 1O2.

PMID- 7626103
TI  - Molecular cloning of the human ryudocan promoter.
AB  - The promoter region of human ryudocan was isolated from a human lambda dash
      genomic library and cloned into pBluescript. The 5'flanking region contained a
      classical TATA box and GC rich regions that are commonly found in constitutively
      expressed genes. Two fusion gene constructs, one of 898 bp and the other of 480
      bp of the 5' flanking DNA coupled to the luciferase gene, were transiently
      expressed in a mouse endothelioma cell line and in human umbilical endothelial
      cell cultures. Both constructs were capable of driving luciferase expression; the
      898 bp construct produced greater levels of luciferase activity than the 480 bp
      construct in both cell types examined. Analysis of the sequence revealed the
      presence of several potential sites for nuclear transcription factor binding; the
      relevance of these sites is presently unknown.

PMID- 7626105
TI  - Early detection of catabolic state via change in 13C/12C ratios of blood
      proteins.
AB  - We find that induction of catabolic state changes the ratios of carbon 13 to
      carbon 12 in blood proteins. Diet can be inferred in growing chicks by feather
      carbon isotope ratios. This suggests an approach for early detection of catabolic
      state induced in patients with HIV, cancers that induce catabolism, infection
      onset, sepsis, kidney and liver disease, malnutrition and dietary problems. The
      technique would also be useful in animal husbandry.

PMID- 7626106
TI  - Identification of an upstream region that controls the transcription of the human
      autocrine motility factor receptor.
AB  - We have isolated from a human placenta cosmid library a 0.7 kb genomic clone that
      contains the 5' terminal portion of the autocrine motility factor receptor
      (hAMFR) coding region. Chloramphenicol Acetyl Transferase (CAT) reporter gene
      assays have identified this region as the promoter of the hAMFR gene. A single
      transcription initiation site (+1) has been mapped to 129 bp upstream of the ATG
      start codon by primer extension. DNA sequence analysis and CAT assay revealed a
      TATA element at the position -485/-468 which was able to conduct only a marginal
      transcription (less than 5% of the total activity). The majority of the hAMFR
      promoter's activity is contributed by a transcription initiator (Inr) element
      overlapping the initiation site (+1) which independently controls the
      transcription of the hAMFR gene. Gel mobility shift assays showed that DNA
      binding proteins in HeLa cells nuclear extract can bind specifically to both
      promoter's elements. DNA-binding proteins were found to be differentially
      expressed by sparse and dense cultured normal fibroblasts. The nuclear-binding
      protein expressed by sparse NIH-3T3 cells induced a DNA mobility shift similarly
      to the nuclear protein of HeLa cells, while a different DNA-protein complex size
      was observed with nuclear proteins extracted from dense cultured NIH-3T3 cells.
      Also CAT-reporter gene analysis revealed a significant lower activity in dense
      NIH-3T3 cells as compared with the sparse-cultured counterparts. These results
      help to explain the previously observed cell-cell contact regulation of AMFR
      expression in normal cells and its consecutive expression in tumor cells.

PMID- 7626107
TI  - A subfamily 2 homo-dimeric glutathione S-transferase mYrs-mYrs of class theta in
      mouse liver cytosol.
AB  - A homo-dimeric subfamily 2 glutathione (GSH) S-transferase (GST) mYrs-mYrs of the
      class theta was isolated from mouse liver cytosol and purified to homogeneity.
      The first 28 N-terminal amino acid sequence of the GST was completely identical
      to that of rat subfamily 2 GST Yrs-Yrs of the class theta. GST mYrs-mYrs cross
      reacted with anti-rat GST Yrs-anti-sera but not with anti-sera raised against rat
      GSTs Ya-Ya (alpha), Yb1-Yb1 (mu), and Yp-Yp (pi) and represented more than 95% of
      the mouse liver cytosolic GST activity to scavenge the reactive sulfate ester 5
      sulfoxymethylchrysene of the potent carcinogen 5-hydroxymethylchrysene. The mouse
      class theta GST had little activity toward 1-chloro-2,4-dinitrobenzene and was
      unretainable on GSH and an S-hexyl-GSH affinity columns. GST mYrs-mYrs had a much
      higher GSH peroxidase activity toward fatty acid hydroperoxides than did the
      other classes of mouse GSTs.

PMID- 7626108
TI  - Molecular cloning and characterization of rat V1b vasopressin receptor: evidence
      for its expression in extra-pituitary tissues.
AB  - Arginine vasopressin (AVP) modulates the secretion of ACTH through vasopressin
      receptor subtype V1b in the pituitary. We recently cloned human V1b, but several
      inconsistencies were found between the characteristics of this cloned receptor
      and those of rat pituitary membrane shown by previous workers. To clarify this
      issue, we report here the molecular cloning and functional expression of the cDNA
      encoding V1b in rat pituitary. This receptor encodes 425 amino acid protein
      having the highest identity with the human V1b (81%). Expression of this receptor
      in COS-1 cells showed pharmacological characteristics of V1b consistent with
      those of rat pituitary membrane. Northern blot and RT-PCR analyses revealed that
      mRNA of this receptor was expressed not only in anterior pituitary, but also in
      other tissues. This finding raises the possibility that V1b may play a role in
      regulating cell functions of these tissues.

PMID- 7626109
TI  - Beta 1-6 branching of N-linked carbohydrate is associated with K-ras mutation in
      human colon carcinoma cell lines.
AB  - Here the K-ras genotypes of nine colon carcinoma cell lines are compared to the
      protein glycosylation patterns found in these cells. By a variety of
      methodologies utilizing lectins to probe carbohydrate structure, we find evidence
      that five out of six cell lines having K-ras mutations have elevated amounts of
      beta 1-6 branching at the trimannosyl core of N-linked carbohydrate. None of the
      three K-ras wild type cell lines assayed have evidence of elevated beta 1-6
      branching. In five out of five cell lines examined, the amount of beta 1-6
      branching correlates with the extent of cellular ras-GTP elevation and supports
      the hypothesis that expression of beta 1-6 branching in colon carcinoma cell
      lines is quantitatively linked to K-ras activation. These results are discussed
      in the context of the ras-signalling pathway.

PMID- 7626110
TI  - Reversion of v-H-ras-transformed NIH 3T3 cells by apigenin through inhibiting
      mitogen activated protein kinase and its downstream oncogenes.
AB  - Apigenin, a plant flavonoid, induced the reversion of transformed phenotypes of v
      H-ras-transformed NIH 3T3 cells at a quite low concentration of 12.5 microM. In
      the present study, we have examined the components of this Ras-mediated signaling
      transduction to determine whether they were involved in the apigenin-induced
      reversion process. Interestingly, the consitutively activated mitogen activated
      protein kinase (MAPK) in the ras transformant was inhibited significantly and
      rapidly by 25 microM apigenin within 30 min, and this reduction continued for
      more than 4 h. Corroborating these observations, expression of the downstream
      oncogenes c-jun and c-fos was also dramatically reduced during the first 4 h of
      treatment. We found that the levels of ras protein and mRNA were not affected by
      24 h of treatment with apigenin. These findings indicate that apigenin-induced
      reversion of v-H-ras-transformed NIH 3T3 cells may occur by inhibiting MAPK
      activity and its downstream oncogenes rather than by affecting the expression of
      the ras gene.

PMID- 7626111
TI  - The interaction of the ferric uptake regulation protein with DNA.
AB  - The interaction of the Ferric Uptake Regulation (Fur) protein with the backbone
      of operator DNA was analyzed by hydroxyl radical footprinting and the ethylation
      interference assay. Comparison of the contacts made by Fur and those made by
      proteins containing the helix-turn-helix or related motifs shows that the mode of
      DNA binding by this repressor is unique. Ethylation interference experiments
      demonstrate that there are relatively few phosphate contacts of unique
      disposition while hydroxyl radical footprinting demonstrates that Fur-operator
      contacts are segregated on one face of the helix and span nearly three successive
      major grooves.

PMID- 7626112
TI  - Inhibition of protein phosphatase 1 and 2A down-regulates beta-tubulin gene
      expression in Trypanosoma rhodesiense.
AB  - We studied the effect of okadaic acid, a specific inhibitor of serine/threonine
      protein phosphatase types 1 and 2A, on the expression of beta-tubulin and
      procyclin genes in Trypanosoma rhodesiense. Okadaic acid was found to decrease
      the steady-state level of beta-tubulin mRNA about 5-fold in differentiating
      bloodstream trypanosomes and about 3-fold in established procyclic trypanosomes.
      No effect was observed on the expression of the procyclin gene. The down
      regulation of beta-tubulin gene expression by okadaic acid in procyclic
      trypanosomes occurs at the post-transcriptional level. These results demonstrate
      the involvement of protein phosphatase 1 and/or 2A activity in maintaining the
      steady-state level of beta-tubulin mRNA in African trypanosomes.

PMID- 7626113
TI  - Laminin-rich extracellular matrix maintains high level of hepatocyte nuclear
      factor 4 in rat hepatocyte culture.
AB  - Laminin-rich extracellular matrix, EHS-gel, has been demonstrated to keep a high
      level of liver-specific gene expression in cultured rat hepatocytes. To obtain
      information about the effect of EHS-gel on liver-specific functions, gene
      expression of liver-enriched transcription factors in rat hepatocytes was
      investigated. The apolipoprotein A-I and albumin mRNA levels were higher in
      hepatocytes cultured on EHS-gel than in those cultured on type I collagen (TIC).
      The levels of mRNA for HNF-4, C/EBP alpha and C/EBP beta were also higher on EHS
      gel than on TIC. The level of HNF-4 mRNA in hepatocytes on EHS-gel was almost
      comparable to that in liver. The HNF-3 alpha mRNA level was lower on EHS-gel than
      on TIC. C/EBP beta mRNA was induced by dexamethasone in both EHS-gel and TIC. The
      induction of C/EBP alpha and HNF-4 by dexamethasone was observed only on TIC.
      These data suggest that EHS-gel leads hepatocytes to keep the phenotypic
      expression through high expression of liver-enriched transcription factors, such
      as HNF-4.

PMID- 7626114
TI  - A novel highly specific and potent inhibitor of calmodulin-dependent protein
      kinase II.
AB  - A novel synthetic peptide AIP (autocamtide-2-related inhibitory peptide), a
      nonphosphorylatable analog of autocamtide-2, was found to be a highly specific
      and potent inhibitor of calmodulin-dependent protein kinase II (CaM-kinase II).
      It was 50 and 500 times more potent than CaMK-(281-302Ala286) and KN-93,
      respectively, under the assay conditions used. The inhibition was unaffected by
      the presence or absence of Ca2+/calmodulin, and it was competitive with
      autocamtide-2 and noncompetitive with syntide-2. AIP (1 microM) completely
      inhibited CaM-kinase II activity, but did not affect cyclic AMP-dependent protein
      kinase, protein kinase C, calmodulin-dependent protein kinase IV, and
      unidentified protein kinases occurring in a rat brain extract. These results
      indicate that AIP is a useful tool for studying the physiological roles of CaM
      kinase II.

PMID- 7626115
TI  - Pentose cycling and the distribution of 13C in trehalose during glucogenesis from
      13C-labelled substrates in an insect.
AB  - Redistribution of 13C in trehalose (Tre) due to pentose cycling was observed in
      vivo in Manduca sexta during glucogenesis from [3-13C]alanine (Ala) and [2
      13C]glycerol (Gly). The extent of cycling was affected by dietary composition.
      Larvae maintained on a low-carbohydrate diet (LCD) exhibited approximately 13%
      cycling, while those on a complete-balanced diet (CBD) or low-fat diet (LFD)
      displayed much higher rates of cycling. Significant incorporation of 13C via
      reversal of the non-oxidative phase was evident on all diets but was greatest on
      the CBD and LFD. In contrast to conclusions from previous studies with insects,
      the present results indicate that under normal conditions the pentose pathway is
      not the principal source of triose phosphates for oxidative catabolism during
      larval development.

PMID- 7626116
TI  - The flavin-containing monooxygenases in rat liver: evidence for the expression of
      a second form different from FMO1.
AB  - A second form of rat liver FMO, FMO-A, was separated and purified by
      chromatography on Blue Sepharose Fast flow 6. This FMO-A is different from FMO1
      by antigenic properties (anti-FMO-A did not cross-react with FMO1, and
      reciprocally) and by catalytic properties (the Km for trimethylamine was 3.8
      microM and 141.4 microM for FMO-A and FMO1, respectively; the Km for imipramine
      was 536 microM and 17.4 microM for FMO-A and FMO1, respectively). Furthermore, N
      terminal amino sequencing revealed differences in the primary structure of these
      two FMOs although they both contained the highly conserved FAD-binding domain
      (Gly-X-Gly-X-X-Gly).

PMID- 7626117
TI  - Characterization of a mutated rubredoxin with a cysteine ligand of the iron
      replaced by serine.
AB  - The active site of rubredoxins consists of a single iron tetrahedrally
      coordinated to four cysteinate sulfurs. One of the iron ligands, cysteine 42, has
      been mutated into serine in Clostridium pasteurianum rubredoxin. This mutation
      resulted in a shift to higher energy of the 320-800 nm region of the UV-visible
      absorption spectrum. Resonance Raman spectra showed that the nu 1 breathing mode
      of the iron chromophore was upshifted as a result of the C42S mutation. The
      spectral pattern, however, was not largely disturbed by the mutation. The EPR
      spectra of both the wild type and the C42S mutated protein displayed the
      characteristic features, at g = 4.3 and g = 9.5, of the "3/2" and "1/2" Kramers'
      doublets, respectively, of a S = 5/2 multiplet. These combined data afford strong
      evidence that in the C42S mutated rubredoxin serine has replaced cysteine 42 as a
      ligand of the iron, while maintaining the tetrahedral coordination of the metal.
      The most spectacular effect of the C42S mutation was a ca. 200 mV downshift of
      the redox potential of rubredoxin.

PMID- 7626118
TI  - A caution about the azide inhibition of enzymes associated with electrophilic
      metabolites.
AB  - Azide is often used as an inhibitor to detect active site metal ions present in
      enzymes such as tyrosinases and laccases. Azide is not only a good chelator for
      metal ions, but also a powerful nucleophile. Consequently, some of the observed
      inhibition of tyrosinase by azide can be explained by the reaction of
      enzymatically generated quinones with azide to form azido catechol. In the light
      of this finding, routine use of inhibition studies with azide to detect the metal
      ions present at the active site of enzymes generating and/or consuming
      electrophilic metabolites is discouraged.

PMID- 7626119
TI  - The developmental regulation of a novel muscle LIM-protein.
AB  - Using a cDNA clone derived from a human muscle library we have identified a novel
      and highly conserved 2.3kb homologue which is highly expressed in skeletal
      muscle. The partial sequence contains at least three LIM domains and shows
      greatest homology with the group of LIM-proteins associated with the cytoskeleton
      and focal adhesion plaques which include zyxin and paxillin. This homologue is
      maximally expressed in differentiated ovine primary muscle cultures. It is also
      expressed in the ovine fetus from at least 50 days of gestation and is
      increasingly upregulated from 120 days of gestation to 8 weeks after birth after
      which it declines. This period corresponds to the period of greatest muscle fibre
      hypertrophy and suggests a role for this homologue in either the elaboration of
      muscle fibre matrix anchorage or the regulation of muscle fibre hypertrophy
      itself.

PMID- 7626120
TI  - Phosphorylation and DNA binding of the octamer binding transcription factor Oct
      3.
AB  - Phosphorylation influences DNA binding and transactivator capabilities of
      multiple transcription factors. In this study, we demonstrate that the POU-domain
      transcription factor, Oct-3, can be phosphorylated in vivo. In addition, we show
      that in COS-1 cells Oct-3 is phosphorylated exclusively on serine residues.
      Lastly, we provide evidence that phosphorylation is not required for Oct-3
      binding to DNA and treatment of Oct-3 with calf intestinal alkaline phosphatase
      does not influence its ability to bind DNA.

PMID- 7626121
TI  - A role for the Gal11 protein in pheromone-induced transcription in Saccharomyces
      cerevisiae.
AB  - The product of the Saccharomyces cerevisiae GAL11 gene, Gal11p, is required for
      the proper expression of a wide range of genes including many mating-type
      specific genes. In this study Gal11p is shown to have a role in the induction of
      transcription by pheromone. Basal transcription of an a-specific gene is
      unaffected by loss of Gal11p but pheromone treatment fails to increase
      transcription. A haploid-specific gene is shown to retain pheromone-inducibility
      in the absence of Gal11p but the extent of induction is drastically reduced.
      Evidence is also presented that suggests the existence of strain differences that
      can alter the phenotype of gal11 mutants.

PMID- 7626122
TI  - Loss of calcium responsiveness in cultured bovine parathyroid cells is associated
      with decreased calcium receptor expression.
AB  - Suppression of PTH secretion by extracellular calcium is mediated by a plasma
      membrane calcium receptor (CaR). However, primary cultures of bovine parathyroid
      cells are known to quickly lose their responsiveness to extracellular calcium.
      The present study was designed to determine if the loss of calcium responsiveness
      is due to changes in CaR expression. In primary monolayer cultures of parathyroid
      cells, calcium-mediated suppression of PTH was still evident after 24 hours in
      culture but was completely absent after 6 days. This was preceded by a 75% drop
      in CaR mRNA content within 24 hours. CaR mRNA levels remained low for the 6-day
      culture. Earlier time points, examined in parathyroid cell suspensions, showed a
      70% drop in CaR mRNA by 4 hours after collagenase-dispersion of the glands and an
      85% drop after 24 hours. The decreased expression of CaR mRNA was not influenced
      by altering medium serum, calcium, or 1,25-dihydroxyvitamin D3. Our results
      indicate that the loss of responsiveness of cultured parathyroid cells to calcium
      is due to decreased CaR mRNA and, presumably, CaR protein expression.

PMID- 7626123
TI  - Subunit sites of oxidative inactivation of Escherichia coli F1-ATPase by HOCl.
AB  - Cellular inactivation of Escherichia coli by the neutrophil-generated toxin,
      hypochlorous acid, is accompanied by inactivation of its plasma membrane
      localized F1-ATPase. The nature of oxidative damage leading to inactivation of
      this enzyme was probed by SDS-PAGE and 2D-gel electrophoresis and by hybrid
      reconstitution studies using purified subunits from untreated and extensively
      oxidized bacteria. The data indicate that inactivation is due to selective
      oxidation of a few highly vulnerable sites; although damage occurred to each of
      the alpha, beta, and gamma-subunits required for soluble ATP hydrolase activity,
      the extent of damage was insufficient to alter their electrophoretic properties.

PMID- 7626124
TI  - Comparison of the ADH7 gene structure in Caucasian and Japanese subjects.
AB  - The ADH 7 gene, encoding the sigma-alcohol dehydrogenase isozyme, was cloned from
      a Caucasian genomic DNA library. Comparison of the nucleotide sequence of its
      exon 7 with that of an ADH 7 previously cloned from a Japanese subject revealed a
      substitution of the glycine-287 in the Caucasian sigma isozyme with valine in the
      Japanese. Since a possible mutation at this site could account for ethnic
      differences in the gastric activity of this isozyme, the frequency of this change
      was examined in both races. The exon 7 of the ADH 7 was amplified by PCR from 7
      Caucasian and 7 Japanese genomic DNA and applied to restriction fragment length
      polymorphism analysis, using Ava II to digest the sequence encoding glycine-287
      and Mae III to digest that encoding valine-287. Regardless of ethnicity, all PCR
      amplicons were digested by Ava II and none by Mae III, suggesting that the ethnic
      difference in the 287 amino acid may represent an uncommon mutation, which does
      not account for the high frequency of minimal activity of the sigma-alcohol
      dehydrogenase in the Japanese stomach compared to those of non-Orientals.

PMID- 7626125
TI  - The NF-kappa B-like site in the TNF-alpha repressor element is essential for its
      repressor function.
AB  - We have previously identified a repressor element in the TNF-alpha promoter (-280
      to -172) by deletion analysis. When this 108 bp repressor element was placed in
      front of a heterologous promoter containing an NF-kappa B binding site, less
      repression was observed. When this element was dimerized and placed in front of
      the positive element (-125 to -102) of the TNF-alpha promoter, instead of
      repression, activation was observed. There is an NF-kappa B-like site in the 108
      bp repressor region (-211 to -202) and our gel retardation analysis showed that
      this site and a known NF-kappa B binding site both could compete for one of the
      specific protein complexes formed on the 108 bp probe. To test the functionality
      of this NF-kappa B-like site, we mutagenized the critical GGGG sequence to ATCC.
      Contrary to our prediction, such a mutation blocked the repressor function of the
      108 bp element. This suggests that the NF-kappa B-like site is an essential
      sequence for the repressor function of the 108 bp repressor element.

PMID- 7626126
TI  - Cyclic AMP-elevating agents negatively regulate the activation of p72syk in N
      formyl-methionyl-leucyl-phenylalanine receptor signaling.
AB  - Here we investigated the involvement of the non-receptor protein-tyrosine kinase
      p72syk in formyl methionyl-leucyl-phenylalanine (fMLP) receptor signaling. The
      activity of p72syk began to rise from 15 s and reached to maximum within 2-5 min
      after 5 microM fMLP stimulation in porcine polymorphonuclear neutrophils (PMNs).
      Cyclic AMP (cAMP)-elevating agents, prostaglandin E2 (PGE2) and forskolin, or
      dibutyryl cAMP partially suppressed p72syk activities stimulated by fMLP in PMNs.
      Pretreatment with an inhibitor of cAMP-dependent protein kinase abolished the
      suppression of the fMLP-induced p72syk activation by these cAMP-elevating agents.
      It was also observed that cAMP-dependent protein kinase phosphorylates p72syk on
      serine residues in vitro. These results indicate a possibility that cAMP
      dependent protein kinase negatively regulates the activation of p72syk in fMLP
      receptor signaling.

PMID- 7626127
TI  - Cloning of rat KATP-2 channel and decreased expression in pancreatic islets of
      male Zucker diabetic fatty rats.
AB  - ATP-regulated potassium channels play a key role in regulating insulin secretion.
      We have isolated cDNA clones from a RINm5F insulinoma cell cDNA library that
      encode a protein, KATP-2, whose sequence shows 72% identity with the rat heart
      potassium channel KATP. RNA blotting showed that KATP-2 mRNA was present at high
      levels in brain and undetectable in heart, spleen, lung, liver, skeletal muscle,
      kidney and testis. A quantitative RT-PCR assay indicated that there were 1.85 +/-
      0.32 x 10(5) molecules of KATP-2 mRNA per microgram of total RNA in pancreatic
      islets from nondiabetic rats. The levels of KATP-2 mRNA were reduced by 34% in
      islets from diabetic Zucker diabetic fatty male rats, a model of non-insulin
      dependent diabetes mellitus, compared to their lean nondiabetic littermates (p <
      0.05), suggesting that decreased expression of KATP-2 may contribute to beta-cell
      dysfunction in this animal model.

PMID- 7626128
TI  - Photodegradation of tryptophan residues and attenuation of molecular chaperone
      activity in alpha-crystallin are correlated.
AB  - The major eye-lens protein alpha-crystallin is known to possess a remarkable
      sequence homology to the low molecular weight heat-shock proteins and has been
      shown to protect several proteins against thermally induced aggregation. In this
      work we demonstrate that the rapid aggregation of rabbit muscle phosphoglycerate
      kinase during incubation at 52 degrees C is completely inhibited in presence of
      1/3 moles alpha-crystallin monomer per mole enzyme. Upon irradiation by UV light,
      tryptophan fluorescence intensity of alpha-crystallin declines, reflecting the
      destruction of these residues. A remarkable correlation is revealed between the
      reduction in alpha-crystallin fluorescence during UV-irradiation and the loss of
      its ability to protect phosphoglycerate kinase against aggregation. Since a loss
      of tryptophan fluorescence in intact eye lenses in vivo has been demonstrated to
      occur upon exposure to UV light, as well as during aging, it is proposed that the
      enhanced rate of lens opacification and cataract formation, as well as the
      increased levels of damaged lens proteins, which accumulate under these
      conditions, are the result of the gradual loss of the chaperone-protein efficacy
      of alpha-crystallin.

PMID- 7626129
TI  - Inhibition of hepatitis C virus replication by antisense oligonucleotide in
      culture cells.
AB  - Oligonucleotides complementary to the sequences containing the initiator codon,
      AUG, of the core region of positive-stranded hepatitis C virus (HCV) were tested
      for their effects on viral translation in a cell-free protein synthesis system
      and on viral replication in a human T-lymphotropic virus type I infected cell
      line, MT-2C, which was cloned by the limited dilution method from MT-2 cells and
      showed more efficient HCV replication than an uncloned population of MT-2 cells.
      Treatment of HCV-infected MT-2C cells with the antisense oligonucleotide (10
      microM) had a dramatic inhibitory effect on viral replication. This result
      suggests that the antisense oligonucleotide complementary to the sequence close
      to the initiation codon of the core region might be useful as an antiviral agent
      against HCV replication.

PMID- 7626130
TI  - Cloning, characterization and expression of a functional mouse ACTH receptor.
AB  - A polymerase chain reaction-generated mouse ACTH-R probe was used to screen a
      mouse genomic library, and a clone of 13kb containing the entire coding sequence
      was isolated. The coding sequence shows 84% homology with the human gene at the
      DNA level and encodes a peptide with 89% homology to the human ACTH-R. This gene
      is expressed as a major transcript of 1.8kb in the mouse adrenal gland. The gene
      was expressed in HeLa cells and cAMP production in response to either ACTH or
      alpha-MSH was measured. cAMP increased in an ACTH dose dependent manner
      suggesting an EC50 of 7 x 10(-10)M ACTH. alpha-MSH was without effect on this
      receptor. In conclusion we have cloned a mouse ACTH receptor gene and
      demonstrated for the first time its expression and functional effect in HeLa
      cells.

PMID- 7626131
TI  - Assignment of disulphide bonds in the X protein (HBx) of hepatitis B virus.
AB  - We have established the disulphide arrangement of cysteines in E. coli expressed
      HBx by chromatographic analysis of enzymatically cleaved protein and sequence
      analysis of cysteine containing fragments. Eight of the nine cysteines are
      disulphide linked in an interesting pattern. Each cysteine is linked to the
      fourth cysteine in a sequential manner and the last cysteine is free; the
      disulphide linkages are between Cys7 and Cys78, Cys17 and Cys115, Cys61 and
      Cys137, Cys69 and Cys143 while Cys148 is free.

PMID- 7626132
TI  - The 5'-untranslated region of human transferrin mRNA, which contains a putative
      iron-regulatory element, is bound by purified iron-regulatory protein in a
      sequence-specific manner.
AB  - Human transferrin mRNA contains a 5'-untranslated region that (1) has homology to
      an iron responsive element and (2) is implicated in translational iron regulation
      of human transferrin transgenes in transgenic mice. Ferritin mRNA contains a 5'
      untranslated region iron-responsive element, but iron regulation of ferritin
      differs from that of human transferrin transgenes in both magnitude and
      direction. Structural differences between the ferritin iron-responsive element
      and the human transferrin putative iron-responsive element may influence their
      iron-regulatory protein interactions and direct the differing translational
      responses. This study examines human transferrin RNA nucleotide sequence
      requirements for binding of cytoplasmic proteins and purified iron-regulatory
      protein. Mutations of the putative transferrin iron-responsive element similarly
      affected binding of purified iron-regulatory protein and liver cytoplasmic
      proteins, providing evidence that the IRP is one of the liver cytoplasmic
      proteins that binds the human transferrin iron-regulatory element and suggesting
      that it may be involved in iron-regulation of transferrin.

PMID- 7626133
TI  - Altered expression of insulin signaling components in streptozotocin-treated
      rats.
AB  - Insulin signaling is known to proceed through the insulin receptor to the insulin
      receptor substrate-1 (IRS-1). Tyrosine-phosphorylation of IRS-1 causes it to
      associate with the src-homology-2 (SH2) domains of at least four other proteins:
      phosphatidylinositol 3'-kinase (PI3K), growth factor receptor-bound protein-2
      (GRB2), Nck, and Syp. In order to understand the cellular derangements associated
      with type I diabetes, the levels of these four SH2-containing proteins was
      determined in streptozotocin-induced diabetic rats. In liver tissue of diabetic
      rats, the levels of Nck and Syp were significantly decreased to 71 +/- 6% and 61
      +/- 4% control, respectively, while in fat tissue only the Syp levels were
      significantly reduced to 72 +/- 9% control. PI3K levels were higher in livers of
      diabetic rats than controls, but unchanged in fat. The insulin-deficient diabetic
      condition was thus associated with altered levels of insulin signaling
      components.

PMID- 7626134
TI  - Alteration of transcription factor binding activities in the ischemic rat brain.
AB  - Transient focal ischemia-reperfusion in the cerebral cortex caused regional
      alteration of DNA-binding activities of transcription factors AP-1, CREB, Sp-1,
      and NF-kB. The changes were time-dependent. During the first 24 hr of reperfusion
      after 90 min ischemia, there was an increase in the binding activity of AP-1 only
      in the region surrounding the ischemic cortex. Five days after ischemia, an
      increase in the binding activities of CREB, Sp-1, and NF-kB, but not AP-1, was
      noted in the ischemic cortex, and to a lesser extent, Sp-1 and NF-kB, in the
      surrounding region. The binding activities of these transcription factors were
      reduced by hydrogen peroxide but could be restored by dithiothreitol and 2
      mercaptoethanol. These results are the first demonstration of ischemia-induced
      differential regulation of transcription factor binding activities which are time
      , region-, and redox state dependent.

PMID- 7626135
TI  - Poisoning by botulinum neurotoxin A does not inhibit formation or disassembly of
      the synaptosomal fusion complex.
AB  - We investigated the effect of poisoning rat brain synaptosomes with botulinum
      neurotoxin A on the NSF-mediated disassembly of a complex consisting of syntaxin,
      SNAP-25 and synaptobrevin (fusion complex). Botulinum neurotoxin A specifically
      removes 9 amino acids from the C-terminus of SNAP-25 and efficiently blocks KCl
      evoked glutamate release from synaptosomes. We report that truncated SNAP-25 is
      incorporated into the fusion complex of poisoned synaptosomes. The presence of
      truncated SNAP-25 does not interfere with the NSF-induced disassembly of the
      fusion complex. Also, the release of truncated SNAP-25 from the fusion complex is
      similar to that of the native SNAP-25. Since neither the formation of the complex
      nor its disassembly seems to be affected by the SNAP-25 fragment, this fragment
      is likely to block exocytosis by disrupting events between disassembly of the
      synaptosomal fusion complex and membrane fusion itself.

PMID- 7626136
TI  - Endothelin-1 stimulates proliferation of normal airway epithelial cells.
AB  - To investigate the influence of endothelins on airway epithelial cell growth, we
      measured [3H]thymidine incorporation and cell numbers of cultured porcine
      tracheal epithelial cells in the presence or absence of endothelin-1 or -3 with
      or without PD-145065 (a combined endothelin-A and -B receptor antagonist), BQ-123
      (an antagonist specific for endothelin-A receptors) or phosphoramidon (an
      inhibitor, in part, of endothelin converting enzymes). We found that endothelin-1
      stimulated the proliferation of airway epithelial cells and this response was
      progressively inhibited by increasing concentrations of either PD-145065 or BQ
      123. In contrast to endothelin-1, airway epithelial cells were not responsive to
      endothelin-3. They also appeared to be producing endothelin-1 endogenously.
      Phosphoramidon significantly decreased basal growth of cells incubated in the
      absence of exogenous endothelin, and was associated with a significant diminution
      in their endothelin production. We conclude that endothelin-1 is mitogenic for
      porcine airway epithelial cells and may be involved in both autocrine and
      paracrine control of them.

PMID- 7626137
TI  - Developmental changes in mRNA encoding cardiac Na+/H+ exchanger (NHE-1) in
      rabbit.
AB  - The faster recovery of cardiac contractility in newborn rabbit hearts during
      acute acidosis compared to adult hearts correlates with greater cellular activity
      of the Na+/H+ exchanger. We quantified mRNA encoding Na+/H+ exchanger-1 (NHE-1)
      in rabbit ventricles of fetal (27 days gestation), newborn (2-5 days), and adult
      (> 6 months) New Zealand white rabbits using reverse transcription-polymerase
      chain reaction (RT-PCR) and RNase protection assay, with GAPD mRNA as standard.
      Both RT-PCR and RNase protection assay revealed similar (p > 0.05) cardiac levels
      of NHE-1 mRNA in fetal and newborn hearts, while NHE-1 mRNA in these hearts was
      1.7x and 1.6x greater than in adult hearts by both RT-PCR and RNase protection
      assay. These developmental changes in NHE-1 mRNA correlate with the developmental
      changes in Na+/H+ activity in sarcolemmal vesicles purified from rabbit heart.

PMID- 7626138
TI  - The cleaved N-terminal signal sequence of the cardiac Na(+)-Ca2+ exchanger is not
      required for functional membrane integration.
AB  - The cardiac Na(+)-Ca2+ exchanger differs from most other polytopic membrane
      proteins in that the amino terminus is cleaved during integration into the
      endoplasmic reticulum membrane. In this study, the cleaved N-terminal signal
      sequence of the exchanger was deleted (DelSS) or rendered uncleavable by mutation
      of the cleavage site (MutSS). Functional analysis of the mutants expressed in
      Xenopus laevis oocytes and sf9 insect cells demonstrates that DelSS exchanger
      catalyzes Na(+)-dependent Ca2+ transport at wild-type levels, while activity of
      MutSS exchanger is reduced to approximately 60% of wild-type in oocytes and 20%
      in sf9 cells. These results indicate that neither the presence nor the cleavage
      of the signal peptide is required for functional assembly of the exchanger
      protein in the membrane. Furthermore, these observations support the concept that
      internal topogenic signals play the major role in membrane insertion of the Na(+)
      Ca2+ exchanger.

PMID- 7626139
TI  - Androgen induction of follicular epithelial cell growth is mediated via insulin
      like growth factor-I from dermal papilla cells.
AB  - Androgen significantly stimulates the proliferation of outer root sheath cells
      that are cocultured with beard dermal papilla cells without cell contact. The
      expression of insulin-like growth factor I (IGF-I) mRNA in beard dermal papilla
      cells was stimulated by androgen and antagonized by cyproterone acetate. Outer
      root sheath cells did not express mRNA for IGF-I either in the presence or
      absence of androgen. Both of these two types of cells expressed mRNA for IGF-I
      receptor and the expression was not affected by androgen. Neutralizing antibody
      against IGF-I antagonized the stimulatory effect of androgen on the growth of
      outer root sheath cell cocultured with beard dermal papilla cells. These findings
      suggest that IGF-I is a candidate for androgen induced hair growth factors.

PMID- 7626140
TI  - [Ambulatory monitoring of arterial pressure in mild hypertensives without
      pharmacologic treatment].
AB  - OBJECTIVE: To evaluate, using a scheme to monitor arterial pressure in out
      patients (MAPOP), how well patients were able to control their light arterial
      hypertension after hygienic-dietary measures had been found insufficient. DESIGN:
      Observational study. SITE. Urban health centre. PATIENTS: 18 people suffering
      from light arterial hypertension and undergoing treatment with hygienic-dietary
      measures only. MAIN MEASUREMENTS AND RESULTS: Out-patient monitoring of arterial
      pressure over 24 hours with an oscillometric model Spacelabs 90202. The arterial
      pressure load or index of average deviation (APL/IAD) was analysed. Two of the 18
      (11%) presented APL values corresponding to normal tension and 11 (61%) had
      values of circadian curve type 1 (APL/IAD < or = 30%). CONCLUSIONS: A high
      percentage (61%) of those patients with light arterial hypertension, whose
      doctors had considered exhausted the possibilities of treatment without drugs,
      showed they could control to an acceptable degree their arterial tension with
      MAPOP: The perfecting and lowering in price of MAPOP systems, along with their
      increasing use in the diagnosis and treatment of patients with hypertension,
      could also provide important savings on pharmaceuticals.

PMID- 7626142
TI  - Complete amino acid sequence of a lectin-related 16.5-kDa protein isolated from
      fruit bodies of a lectin-deficient strain of Pleurotus cornucopiae.
AB  - The complete amino acid sequence of a lectin-related 16.5-kDa protein (PCL-RP)
      isolated from fruit bodies of a lectin-deficient strain of P. cornucopiae is
      presented. The sequences of six out of the seven peptides generated by digestion
      with lysylendopeptidase and four of the five peptides generated by cyanogen
      bromide cleavage were completely analyzed. Overlapping peptides were obtained by
      arginylendopeptidase digestion. PCL-RP was a single-chain protein consisting of
      144 amino acid residues and its N-terminal serine was blocked with acetate. A
      proline-rich sequence was found in the carboxyl terminal portion. The N-terminal
      sequence of PCL-RP showed some homology with those of two known Basidiomycete
      lectins.

PMID- 7626141
TI  - Structure of a new nucleic-acid-binding motif in eukaryotic transcriptional
      elongation factor TFIIS.
AB  - Transcriptional elongation involves dynamic interactions among RNA polymerase and
      single-stranded and double-stranded nucleic acids in the ternary complex. In
      prokaryotes its regulation provides an important mechanism of genetic control.
      Analogous eukaryotic mechanisms are not well understood, but may control
      expression of proto-oncogenes and viruses, including the human immunodeficiency
      virus HIV-1 (ref. 8). The highly conserved eukaryotic transcriptional elongation
      factor TFIIS enables RNA polymerase II (RNAPII) to read though pause or
      termination sites, nucleosomes and sequence-specific DNA-binding proteins. Two
      distinct domains of human TFIIS, which bind RNAPII and nucleic acids, regulate
      read-through and possibly nascent transcript cleavage. Here we describe the three
      dimensional NMR structure of a Cys4 nucleic-acid-binding domain from human TFIIS.
      Unlike previously characterized zinc modules, which contain an alpha-helix, this
      structure consists of a three-stranded beta-sheet. Analogous Cys4 structural
      motifs may occur in other proteins involved in DNA or RNA transactions, including
      RNAPII itself. This new structure, designated the Zn ribbon, extends the
      repertoire of Zn-mediated peptide architectures and highlights the growing
      recognition of the beta-sheet as a motif of nucleic-acid recognition.

PMID- 7626143
TI  - [Polyarthritis as a complication of the treatment with intravesical BCG].

PMID- 7626144
TI  - Solid-state fermentation of agricultural wastes into food through Pleurotus
      cultivation.
AB  - The technical feasibility of using agricultural wastes (mango and date industry
      wastes) as a substrate for the cultivation of Pleurotus ostreatus NRRL-0366 is
      evaluated. When comparing the biological efficiency of mushroom production, the
      highest yield of fruiting bodies was obtained using a mixture of date waste and
      rice straw at a ratio (1:1) (11.96%), followed by a mixture 3:1 (11.16%). The
      lowest one was the mixture 2:1 (9.19%). Fungus Pleurotus ostreatus NRRL-0366 can
      also be cultivated on mango waste supplemented with rice straw at a different
      ratio. The best one was the 1:1 mixture (10.18%), whereas the lowest was a
      mixture 3:1 (6.4%). Comparing the results obtained favored the use of date waste
      as a substrate for growing Pleurotus ostreatus NRRL-0366. Spawn was cultured on
      three different substrates as follows: Date waste alone (I); 1:1 (by wt) date
      waste and rice straw (II); 1:1:1 date waste, rice straw, and corncobs (III).
      Final dry weight and composition of the fruiting bodies are tabulated for the
      three sets of conditions. Date waste and rice straw mixture (II) is a good source
      of nonstarchy carbohydrate (67%) and protein (27.44%) containing amounts of
      essential amino acids, especially lysine and low RNA (3.81%). Elemental analysis
      were studied in the fruit bodies of the three media.

PMID- 7626145
TI  - The Wilson disease gene: spectrum of mutations and their consequences.
AB  - We have previously reported the cloning of a gene that encodes a copper
      transporting P-type ATPase (ATP7B) which is defective in Wilson disease. We have
      now identified in 58 WND patients, 20 new mutations as well as three of five
      previously published mutations: 11 small insertions and deletions, seven
      missense, two nonsense and three splice site mutations. Two of the mutations are
      relatively frequent, representing 38% of the mutations in patients of European
      origin. Our findings suggest a wider spectrum of age of onset than is considered
      typical of Wilson disease: mutations that completely disrupt the gene can produce
      liver disease in early childhood when Wilson disease may not typically considered
      in the differential diagnosis. The mutations identified provide an explanation
      for at least part of the wide phenotypic variation observed in Wilson disease.

PMID- 7626146
TI  - Effect of CCK-B/gastrin receptor antagonist on pepsinogen-producing cells during
      omeprazole treatment.
AB  - The present study investigated the effect of long-term treatment with omeprazole
      on pepsinogen-producing cells and examined whether the selective CCK-B/gastrin
      receptor antagonist was able to prevent the omeprazole-induced changes, if
      occurred, in rat stomach. Rats were treated with omeprazole and/or the CCK
      B/gastrin receptor antagonist for 28 days. As a result, omeprazole markedly
      reduced mucosal pepsinogen activity and its mRNA concentration in rat stomach.
      Morphologically, in fundic glands omeprazole drastically decreased the proportion
      of mature chief cells and reciprocally increased that of immature chief cells
      which were positive for class III mucin. These effects of omeprazole were
      attenuated by an addition of the CCK-B/gastrin receptor antagonist. Our results
      suggest that omeprazole retards the differentiation of chief cells in fundic
      mucosa probably through hypergastrinemia in adult rat.

PMID- 7626147
TI  - A molecular mechanism for stress-induced alterations in susceptibility to
      disease.
AB  - Corticotropin-releasing hormone (CRH) is a 41-amino acid peptide which mediates
      behavioural and physiological responses to stress. A major target of CRH is the
      proopiomelanocortin (POMC) gene. Three transcription factors have been identified
      that affect transcription of the POMC gene by binding to two different sites
      within the CRH-responsive element of that promoter. We searched Genbank and found
      that nucleotide sequences in the POMC promoter which bind POMC-transcription
      factors are also contained in the genome of HIV-1 and cytomegalovirus, in c-fes
      and human MAT-1 breast cancer oncogenes, and in proinflammatory molecules, such
      as the interleukin-1 beta converting enzyme. We hypothesise a mechanism of
      hormone action by which a peptide hormone, such as CRH, might affect disease
      susceptibility by eliciting the production of transcription factors which may
      bind to unexpected intracellular targets, such as viruses, oncogenes, or the
      genes encoding for inflammatory mediators. Infection, inflammation, and possibly
      neoplastic transformation would thus be facilitated. This hypothesis can be
      tested. If confirmed, CRH antagonists may prove useful in the treatment of
      disorders whose pathophysiology involves molecules that respond to CRH-regulated
      POMC transcription factors.

PMID- 7626148
TI  - A program plan addressing carpal tunnel syndrome: the utility of King's goal
      attainment theory.
AB  - 1. Today's nurse is prepared to address the needs of groups of individuals who
      share common characteristics or risks (aggregates). Program planning skills and
      ability to use nursing theory can enhance the nurse's effectiveness in addressing
      the needs of such aggregates. 2. Carpal tunnel syndrome and other repetitive
      stress injuries are very costly to industry, both in terms of monetary loss and
      lost work hours. Such injuries can be reduced in the workplace through careful
      observation and communication of trends by the nurse. 3. The systems perspective
      of King's goal attainment theory guided the nurse in problem solving and
      facilitating the development of a workplace capable of responding to trends as
      they occur.

PMID- 7626150
TI  - Petro-Canada Heart Health Program: successful program.
AB  - 1. The economic impact of cardiovascular disease is significant, requiring 8.3
      million annual inpatient days for treatment. Disability accounts for 25% of
      disability pensions paid by Canada Pension Plan to individuals less than 65 years
      of age. 2. Management of risk factors provides an opportunity to reduce the
      likelihood of coronary heart disease (CHD) and to mitigate the effects of non
      modifiable risks. 3. There is an increased risk for CHD with elevated
      cholesterol. The best return on the value of a cholesterol program comes from
      testing work groups comprised mainly of males and older employees. 4. The goal of
      promoting and maintaining high levels of physical, mental, and social well being
      for workers can be achieved through programs such as the cholesterol screening
      and education programs.

PMID- 7626149
TI  - Preparing nursing students for practice: successful implementation of a clinical
      practicum in occupational health nursing.
AB  - 1. Nursing's Agenda for Health Care Reform, The Year 2000 Health Objectives for
      the Nation and the Pew Health Professions Commission support the provision of
      primary care in the workplace. 2. The faculty in the department of nursing wanted
      to provide learning experiences for community health nursing students that would
      allow students to develop the skills of teaching, program planning, and
      development and assessment of exposure to environmental hazards. 3. Members of an
      Association of Occupational Health Nurses constituent organization were invited
      to participate in the planning and development of appropriate learning
      activities.

PMID- 7626151
TI  - Managed care in workers' compensation: analysis of cost drivers and vendor
      selection.
AB  - 1. Managed care for employee benefits provides a model of cost containment for
      workers' compensation; however, significant differences must be understood. 2.
      Purchasers of managed care services must perform an internal assessment to
      determine the cost drivers for workers' compensation. Managed care does not
      address all cost drivers. 3. A model for evaluating managed care vendors places
      them on a continuum of risk, similar to insurance risk, where a variety of cost
      containment strategies may be used together. 4. By reviewing seven key aspects of
      a managed care vendor, a purchaser can rate the vendor's ability to meet their
      needs.

PMID- 7626152
TI  - Lead toxicity--by the Agency for Toxic Substances and Disease Registry.

PMID- 7626153
TI  - Precepting students.

PMID- 7626155
TI  - Toward a Global Consensus on Quality Medical Education: Serving the Needs of
      Populations and Individuals. Proceedings of the 1994 World Health
      Organization/Educational Commission for Foreign Medical Graduates Invitational
      Consultation. Geneva, Switzerland, October 3-6, 1994.

PMID- 7626154
TI  - Panic disorder treatment and referral: information for health care professionals.

PMID- 7626156
TI  - International medical education and the concept of quality: historical
      reflections.
AB  - After offering reflections on the words "global" and "international," this paper
      presents examples supporting the observations that physicians have long crossed
      national boundaries in a quest for learning and that dominant nations have long
      brought their perceptions of quality to institutions of medicine elsewhere. It
      then discusses cross-cultural issues in defining quality in medicine and in
      medical education; although some technical aspects of medicine span national
      boundaries, medical practice has a large cultural component. Tension is noted
      between forces favoring international standardization in medicine--for example,
      the communication revolution and the desire for international control of
      infectious diseases--and forces favoring variation among cultures.

PMID- 7626157
TI  - Prospects for change in medical education in the twenty-first century.
AB  - With Health for All as a social goal and a reference point, medical schools must
      create new alliances within the health sector and with other sectors bearing on
      health. The future role and responsibility of the medical school should reflect
      the likely essential features of the future health system and the aptitudes that
      medical practitioners will have to possess. Medical schools should be encouraged
      not only to shape their educational programs accordingly, but also to devote
      energy and resources to the considerable task of creating opportunities for this
      new practitioner. Quality in medical education results from a coordinated effort
      to ensure relevance and efficiency in the education of future doctors and to
      ensure these doctors' optimal fit in society. Implicit in the notion of quality
      is a special consideration for social accountability. A medical school shows
      social accountability through its commitment to addressing issues, or helping
      solve problems, identified jointly with society as priorities for both the
      present and the longer term, in the expectation that the medical school's action
      will benefit in part the local community and in part the country as a whole or
      the international community. Indicators of quality in medical education, as well
      as measurement tools, must be developed and tested in various sociocultural
      contexts. A taxonomy to assess the social accountability of medical schools is
      proposed.

PMID- 7626158
TI  - A vision of quality in medical education.
AB  - This paper begins with historical and other reflections on the nature and
      importance of quality in medical education. It then identifies and discusses
      missions of a medical school--which include teaching, research, medical service,
      continuing education, and social advocacy--and notes that these elements should
      be complementary and indeed synergistic. Components of quality, both of a medical
      graduate and of a medical school, are then considered. After discussing the use
      of examinations to assess quality of graduates, the paper concludes by calling
      for a total quality approach to medical education, with due attention to input,
      process, and output.

PMID- 7626159
TI  - Medical education in the 1990s--and beyond: a view from the United States.
AB  - American medical education is under continued study, and reforms are being
      suggested to improve it. The current paper reviews the standard U.S. medical
      school curriculum and discusses suggestions for change. Medical education must
      become more student- and learning-oriented, must place more emphasis on primary
      care, and must use new settings for education. The paper also examines the
      reasons that medical schools fail in their education mission.

PMID- 7626160
TI  - Establishing standards and measurement methods for medical education.
AB  - This paper focuses largely on describing the accreditation system recently
      instituted for medical schools in Australia. Features of the system include
      evaluation of medical schools in terms of their own objectives and emphasis on
      the accreditation process as a consultation rather than an inspection. Steps in
      the accreditation process are as follows: briefing of the medical school, the
      school's preparation of a database on itself, a five-day assessment visit by a
      team of senior academics, immediate oral presentation of a preliminary report to
      the medical school, preparation of a written report, and awarding of
      accreditation for up to ten years. The paper also briefly describes the Community
      Based Education and Service (COBES) program, in which medical students at the
      University of Ilorin (in Nigeria) live, study, and work in villages for one month
      per year. The paper ends by noting the need to balance, on the one hand, defining
      and assessing those aspects of medical education important anywhere in the world
      and, on the other hand, addressing local context and relevance.

PMID- 7626161
TI  - Quality assurance in medical education.
AB  - Many people have an interest in the quality of medical education. Students have
      the right to as good an education as possible, and the public has the right to
      well-educated and well-trained general physicians and specialists. Therefore, a
      medical school or faculty must ensure its quality and is accountable for the
      quality of the training it provides. This paper emphasizes that the best way to
      ensure quality is by continuous attention to it. Quality depends not on
      measurement instruments and tools but rather on the spread of quality awareness
      among faculty, staff, and students. A tool for safeguarding quality is the design
      of a well-functioning quality assessment system, based on two pillars: a system
      of internal quality control and external assessment by peers. The connection
      between the internal and external assessments is the self-evaluation by the
      school. On the one side, this self-evaluation is a critical self-analysis and an
      agenda for improvement. On the other side, it contains information for the
      external reviewers. The peer review also provides input for the process of
      improvement.

PMID- 7626162
TI  - Toward a global consensus on quality medical education: serving the needs of
      populations and individuals.

PMID- 7626163
TI  - Quinoxaline chemistry. Part 4. 2(R)-anilinoquinoxalines as nonclassical
      antifolate agents. Synthesis, structure elucidation and evaluation of in vitro
      anticancer activity.
AB  - Thirty-five quinoxalines bearing a substituted aniline group on position 2 and
      various substituents on positions 3,6,7 and 8 were prepared in order to evaluate
      in vitro anticancer activity. Structural elucidation of some isomeric
      quinoxalinones formed by ring closure of 4-substituted-1,2-diaminobenzenes with
      dicarbonyl compounds was achieved by comparison with one isomer coming from an
      unambiguous independent route. Preliminary in vitro screening at NCI showed that
      many compounds exhibited a moderate to strong growth inhibition activity on
      various cell lines between 10(-5) and 10(-4) molar concentrations.

PMID- 7626164
TI  - Analgesic, antimuscarinic activity and enantioselectivity of the four isomers of
      3-quinuclidinyl tropate as compared with the enantiomers of hyoscyamine.
AB  - The four stereoisomers of 3-quinuclidinyl tropate (2) were synthesized and their
      absolute configuration established. The analgesic activity of the four isomers on
      the hot-plate test and their muscarinic antagonism on rabbit vas deferens (M1),
      guinea-pig heart (Force, M2) and ileum (M3) and on the muscarinic receptors
      present in immature guinea-pig uterus were evaluated. The results were compared
      with those of the enantiomers of hyoscyamine (1). No apparent correlation was
      found between the analgesic activity and antimuscarinic activity on M1, M2 and M3
      receptors, whereas striking differences exist between the affinity values of the
      analgesic enantiomer of hyoscyamine (R-(+)-1) and those of the inactive isomers
      of 2 on the muscarinic receptor present in immature guinea pig uterus. Molecular
      Modelling studies have shown that the only difference between 1 and 2 lies in the
      volumes occupied by the basic part of the molecules.

PMID- 7626165
TI  - Synthesis of 3-(2'-furoyl)indole derivatives as potential new ligands at the
      benzodiazepine receptor, structurally more restrained analogues of
      indoleglyoxylylamides.
AB  - A number of furoylindoles were synthesized with the aim of obtaining structurally
      more restrained analogues of the previously described indoleglyoxylylamides,
      which are high affinity ligands at the benzodiazepine receptor. In these new
      compounds, the oxygen atom of the oxalyl CO(2) is inserted into the rigid furan
      ring. However, unlike the glyoxylylamides, they proved to be incapable of
      interacting with the benzodiazepine receptor. To rationalize these results,
      molecular electrostatic potentials were calculated; these indicated a positive
      electrostatic potential region for the furan oxygen, which thus prevents the
      formation of a hydrogen bond necessary for interaction with the receptor.
      Nevertheless, these findings confirmed that the CO(2) of the indoleglyoxylylamide
      derivatives represents one of the principal points of interaction with the
      receptor site for these kinds of ligands, as previously hypothesized by us.

PMID- 7626166
TI  - Synthesis and evaluation of aminoadamantane derivatives for in vitro anti-HIV and
      antitumor activities.
AB  - The synthesis of a series of 2-aminobenzimidazole and indole amide derivatives
      containing the adamantyl moiety is described. The compounds, evaluated for in
      vitro anti-HIV and antitumor activities, were found to be moderately active or
      inactive, versus drug-treated controls, used for comparison purposes.

PMID- 7626167
TI  - Synthesis and biological evaluation of 6-carboxy-3,4-methanoprolines, new rigid
      glutamate analogs.
AB  - 6-Carboxy-3,4-methanoprolines were prepared by reacting ethyl diazoacetate with
      the suitable 3,4-didehydroproline derivative in the presence of
      rhodium(II)acetate dimer as catalyst. The affinities of the title compounds for
      displacement of receptor binding to ionotropic and metabotropic (mGluR1 alpha)
      glutamate receptors were also determined.

PMID- 7626168
TI  - A new class of antibronchospastic agents: 7-(2,2-dimethyl)propyl substituted
      xanthines.
AB  - A series of 7-(2,2-dimethyl)propyl substituted xanthines were synthesized and
      tested for their antibronchospastic activity in comparison with theophylline. In
      vitro, the inhibition of carbachol-induced increase in bronchial tone was
      determined. In vivo, the inhibition of antigen-induced bronchoconstriction in
      guinea pigs was determined 1, 3 and 5 h after oral administration. Central side
      effects were evaluated. In vitro, the majority of compounds were more effective
      than theophylline. In vivo, three compounds 2, 14 and 15 showed an effect
      comparable to theophylline but longer lasting. A mild sedative effect was
      generally observed. Compound 2, 7-(2,2-dimethyl)propyl-1-methyl xanthine, coded
      MX2/120, was selected for a deeper evaluation.

PMID- 7626169
TI  - Nonsteroidal antiinflammatory agents. XXIII. Synthesis and activity of
      stereomeric (+/-)-erythro- and (+/-)-threo-2-(4-biphenylyl)-3-hydroxy-2-methyl-3
      phenyl-propionic acids.
AB  - In pursuing our research on the NSAIDs, the diastereomeric (+/-)-erythro- and (+/
      )-threo-2-(4-biphenylyl)-3-hydroxy-2-methyl-3-phenyl-propionic acids (4 and 5)
      were synthesized; the last was also resolved in its optical isomers (6 and 7).
      The attribution of the relative configuration to 4 and 5 was performed by means
      of X-ray analysis. The compounds were tested for their antiinflammatory activity.
      The acid 4, which resulted very interesting, was tested also for analgesic and
      antipyretic activity, as well as for behavioural effects, gastric tolerability
      and acute toxicity. On the basis of the obtained data, this compound resulted a
      very promising one.

PMID- 7626170
TI  - Research on heterocyclic compounds. XXXIII--Synthesis and analgesic activity of
      imidazo[1,2-b]pyridazine-2-acetic acid derivatives.
AB  - A series of imidazo[1,2-b]pyridazine-2-acetic esters, acids 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 4-chloroacetoacetate, followed by hydrolysis or
      ammonolysis in order to obtain the corresponding acids and amides. The capacity
      of inhibiting the carrageenan-induced edema in the rat paw and the writhes
      induced by acetic acid in mice were evaluated, as well as the ulcerogenic action
      in rats. The acidic derivatives showed significant analgesic activity which is
      comparable to that found in other series of imidazo[1,2-b]pyridazine analogs
      previously examined.

PMID- 7626171
TI  - Synthesis and antiarrhythmic properties of basic amide derivatives of
      imidazolidine-2,4-dione and pyrrolidine-2,5-dione II.
AB  - Basic amide derivatives of imidazolidine-2,4-dione and pyrrolidine-2,5-dione were
      synthesized as potential antiarrhythmic agents. Some of them have shown
      antiarrhythmic activity in the chloroform, barium chloride or adrenaline induced
      arrhythmia.

PMID- 7626172
TI  - Synthesis of some N,N-disubstituted carbamodithioic acid esters tested for
      antifungal activity.
AB  - The synthesis of 12 new 4-[(N,N-disubstituted
      thiocarbamoylthio)acetamido]antipyrines and their antifungal activity are
      reported. Of these compounds, only 3e, showed good antifungal activity against C.
      tropicalis KUEN 1021, C. krusei KUEN 1001, C. stellatoidea KUEN 1018, C.
      pseudotropicalis KUEN 1012, C. albicans ATCC 10231 when compared with
      clotrimazole and miconazole (MIC = 12.5 micrograms/ml).

PMID- 7626173
TI  - Insulin and glucagon levels in living related liver transplantation: their
      interaction with the recovery of graft liver function.
AB  - Insulin and glucagon have opposite effects on various hepatic functions,
      including energy metabolism, which is essential for hepatic viability. To
      evaluate the effects of insulin and glucagon on the recovery of graft liver
      function, changes in these levels were investigated in relation to arterial
      ketone body ration (AKBR) during a 30-h period after graft liver reperfusion in
      29 recipients of living related liver transplants. Insulin levels did not change
      significantly throughout this study, while glucagon levels decreased immediately
      after reperfusion, indicating a rapid degradation of glucagon by the graft liver.
      The insulin/glucagon (I/G) ratio increased after reperfusion concomitantly with
      AKBR. In addition, the I/G ratio was significantly correlated with AKBR after
      reperfusion. It is concluded that the increase in the I/G ratio was closely
      related to the recovery of graft liver function as reflected by the AKBR in
      living related liver transplantation.

PMID- 7626174
TI  - Human herpesvirus-6 infection in renal allografts: retrospective
      immunohistochemical study in Japanese recipients.
AB  - This study was conducted to determine the incidence and clinical significance of
      human herpesvirus-6 (HHV-6) infection in renal allografts. A total of 105 biopsy
      specimens from 72 recipients were immunohistochemically examined for the presence
      of HHV-6 antigen, which localized in the distal tubular epithelial cells and in a
      few lymphocytes infiltrating into the interstitium. HHV-6 antigen in the tubular
      epithelia was detected in 63 (61.2%) specimens. Categorically, a higher incidence
      of the antigen was noted in specimens of accelerated rejection (3/4, 75.0%),
      acute rejection (28/3, 73.7%), and cyclosporin nephropathy (8/11, 72.7%). The
      antigen was present and absent an almost equal number of times in the categories
      of chronic rejection, intraoperative and routine protocol biopsies. Repeated
      biopsies were performed in six cases showing HHV-6 antigen, only one of which
      underwent transplant nephrectomy due to severe chronic rejection. Single or
      multinucleated giant cells in distal tubuli occurred in 10 (9.5%) specimens in a
      scattered manner. All of them were diagnosed as acute or chronic rejection. The
      giant cells showed no immunoreactivity for HHV-6, cytomegalovirus, or herpes
      simplex virus. These results indicate overall that HHV-6 infection is common in
      renal allografts and might be reactivated in acute rejection or cyclosporin
      nephropathy. The presence of HHV-6 antigen, however, does not necessarily
      correlate with a poor prognosis for the renal graft nor with the occurrence of
      giant cells in distal tubuli.

PMID- 7626175
TI  - Effects of taurine on liver preservation in UW solution with consecutive ischemic
      rewarming in the isolated perfused rat liver.
AB  - Taurine (2-aminoethane sulfonic acid) is a physiologic amino acid involved in
      cellular osmoregulation in various species including man. This study was intended
      to compare the respective effects of cold storage and consecutive ischemic
      rewarming of the liver postischemic hepatic flow and hepatocellular outcome upon
      reperfusion with or without the addition of taurine to the preservation medium.
      Livers from male Wistar rats were rinsed free of blood via the portal vein and
      stored ischemically at 4 degrees C in UW solution. Livers from group 1 were then
      rinsed again with 10 ml Ringer's solution and reperfused with Krebs-Henseleit
      buffer at a constant pressure of 10 mmHg for 45 min at 37 degrees C in a
      nonrecirculating manner. Livers from groups 2 and 3 were subjected to 30 min of
      warm ischemia subsequent to cold storage and prior to reperfusion with 10 mM
      taurine added to the UW solution in group 3. While there were only very few signs
      of hepatic injury in group 1, the additional period of warm ischemia (group 2)
      led to a significant reduction in early perfusate flow and enhanced enzyme
      leakage from the livers during postischemic rinse and reperfusion. Livers in
      group 3 exhibited an amelioration in hepatic circulation and significantly
      reduced enzyme release as compared to group 2. The results clearly demonstrate a
      remarkable impact of postischemic rewarming on graft viability. Furthermore, the
      addition of taurine to the preservation medium was shown to improve hepatic
      circulation and enhance viability of the liver upon reperfusion.

PMID- 7626176
TI  - HLA-DP antibodies in patients awaiting renal transplantation.
AB  - Sera from 505 patients awaiting renal transplantation with known panel-reactive
      cytotoxic antibody (PRA) status were tested for HLA-DP antibodies of the IgG
      class by means of the monoclonal antibody immobilization of leukocyte antigens
      (MAILA) technique. The overall incidence of HLA-DP antibodies was 7.3%. A
      positive HLA-DP antibody status correlated only weakly (r = 0.23) with a positive
      cytotoxic antibody status. After retrospective analysis, patients with HLA-DP
      antibodies prior to retransplantation revealed a significantly (P < 0.025) higher
      graft function rate than HLA-DP-negative patients. One patient was found to
      possess IgG HLA-DP autoantibodies prior to transplantation; thus far, his graft
      has been functioning for more than 2 years.

PMID- 7626177
TI  - Outcome following organ removal from poisoned donors: experience with 12 cases
      and a review of the literature.
AB  - From 1975 to 1993, our University Hospital performed 2789 graft procedures.
      During the same period, 12 poisoned, "brain-dead" patients were considered as
      organ donors. The toxic substances involved were: methaqualone (n = 1),
      benzodiazepine alone (n = 1), benzodiazepine plus tricyclic antidepressants (n
      =1), tricyclic antidepressants alone (n = 1), barbiturates (n = 2), insulin (n =
      2), carbon monoxide (n = 1), cyanide (n = 1), methanol (n = 1), and acetaminophen
      (n = 1). From these intoxicated persons, 32 organ transplants were obtained, but
      only 23 could be followed for 1 month and only 20 for 1 year. The outcome at 1
      month was favorable in 20 of the 23 patients. Two heart transplant patients died
      with 24h after grafting from stroke and acute heart failure, respectively.
      Preoperative hepatic encephalopathy was not corrected after grafting and was
      directly responsible for the death of a liver transplant patient. After 1 year,
      15 of the 20 recipients were still alive. Chronic hepatic graft rejection led to
      a fatal outcome in one recipient and to second grafting in another. Finally, one
      recipient died from delayed neoplasia. Based on our experience, organ procurement
      may be considered in a few select cases of acute poisoning. Attention should,
      however, be drawn to possible graft damage due to some poisons.

PMID- 7626179
TI  - Timing and quantification of bone loss in cardiac transplant recipients.
AB  - To evaluate osteopenic bone disease in heart transplant patients, we
      prospectively measured bone mineral density (BMD) in 33 consecutive male
      recipients before hospital discharge and 1 year later, using dual photon
      absorptiometry. At hospital discharge BMD measurement at the lumbar spine was 90%
      of that expected in healthy age- and sex-matched controls (p = 0.005). One year
      later BMD had further decreased by 8.5% at the lumber spine and by 10.4% at the
      femoral neck (P = 0.0001). Five patients suffered vertebral compression fractures
      during the 1st postoperative year. Our results indicate that osteopenia of the
      lumbar spine is already present at the time of hospital discharge after
      transplantation and that further bone loss occurs at considerable rate during the
      1st postoperative year at the lumber spine and at the femoral neck.

PMID- 7626180
TI  - Venous air embolism, preservation/reperfusion injury, and the presence of
      intravascular air collection in human donor livers: a retrospective clinical
      study.
AB  - In human liver transplantation, air embolism is seldom encountered after graft
      reperfusion. Nevertheless, despite adequate flushing and clamping routines, air
      emboli have been reported in transesophageal echocardiography (TEE) studies
      performed during the reperfusion phase. We retrospectively investigated whether
      air in the donor liver -- as observed with pretransplant magnetic resonance
      imaging (MRI) -- resulted in clinical air embolism or contributed to
      preservation/reperfusion injury. Clinical air embolism was assessed by
      intraoperative hemodynamics and end-tidal CO2 monitoring.
      Preservation/reperfusion injury was assessed in postoperative biochemical
      measurements. The outcomes were compared between patients receiving livers
      containing significant intrahepatic air and patients receiving livers without
      intrahepatic air. Forty-three livers were studied, seven which had major
      intrahepatic air and ten of which had no evidence of air collections. Twenty-six
      livers showed minor amounts of air and were excluded from further study. One
      patient who received a liver that did not contain intrahepatic air had clinical
      evidence of air embolism. Clinical air embolism did not appear to be associated
      with the presence of significant intrahepatic air based upon pretransplant MRI.
      Intrahepatic air did not seem to affect the amount of preservation/reperfusion
      injury. Our data indicate that air bubbles in the portal and arterial branches
      are absorbed during reperfusion and that the majority of intrahepatic air is
      effectively removed by the specific flushing routines.

PMID- 7626178
TI  - Lipoprotein profile after combined kidney-pancreas transplantation in insulin
      dependent diabetes mellitus.
AB  - In order to evaluate the effect of a combined kidney-pancreas (KP)
      transplantation in insulin-dependent diabetes mellitus (IDDM) patients on the
      lipid and lipoprotein profile, 15 KP patients were compared with 11 kidney (K)-
      transplanted IDDM patients, 19 IDDM patients on hemodialysis (HD), and 15
      nondiabetic control subjects. Cholesterol, triglycerides, apo AI, and apo B were
      measured in total plasma and in VLDL, LDL, and HDL of all participants. VLDL
      cholesterol, VLDL-triglycerides, and VLDL-apo B were significantly lower in KP
      patients, but not in K patients, than in HD patients. In addition, patients in
      the K, but not in the KP, group showed high levels of apo B in LDL and an
      increased triglyceride/apo B ratio in VLDL, compared with patients in the HD
      group. The percentage of apo AI associated with HDL was significantly higher in
      both transplanted groups than in the HD group. However, compared with a
      nondiabetic control population, an increase in VLDL particles and in triglyceride
      content in LDL and HDL still persisted following combined KP transplantation.
      Insulin resistance (probably due to steroid therapy) associated with high
      peripheral and potentially low hepatic insulin levels (due to the systemic
      drainage of the transplanted pancreas) could be the main causes of the remaining
      lipoprotein abnormalities.

PMID- 7626181
TI  - Protection of canine renal grafts by renin-angiotensin inhibition through
      nucleoside transport blockade.
AB  - The aims of this study were (1) to investigate the effect of R 75231, a
      nucleoside transport inhibitor, on renin-angiotensin release after renal ischemia
      reperfusion and (2) to establish a possible protective effect of this drug on
      renal function. We used a canine model for auto- transplantation of kidneys that
      had been subjected to 30 min of warm ischemia and subsequently to 24h of cold
      storage in HTK preservation solution, with immediate contralateral nephrectomy. R
      75231 was injected intravenously into six dogs in two equal portions of 0.05
      mg/kg both 30 min and 10 min before reanastomosis was established. Another six
      dogs were used as a control group. At 2 weeks post-transplantation, five out of
      six dogs in the R 75231 group and one out of six in the control group were still
      alive. Starting on day 4, serum creatinine was lower in the R 75231 group than in
      the control group (p < 0.005). In contrast to the control group, an inversion of
      the median preischemia adenosine/inosine ratio was observed in the R 75231 group
      after reperfusion (0.4 preischemia vs 4.0 after 60 min of reperfusion).
      Reperfusion of the graft resulted in an immediate increase in renin, angiotensin
      I, and angiotensin II venous blood levels in the control group. In the R 75231
      group, renin, angiotension I, and angiotensin II levels were significantly lower.
      We conclude that administration of R 75231 before reperfusion has a protective
      effect on post-transplant function of kidneys that have been subjected to
      prolonged warm ischemia. This effect may, at least in part, be ascribed to
      inhibition of the breakdown and disposal of endogenous adenosine which, in turn,
      inhibits the excessive stimulation of the renin-angiotensin system in the early
      phase of reperfusion.

PMID- 7626182
TI  - The clinical significance of post-transplantation non-HLA antibodies in renal
      transplantation.
AB  - This study was undertaken to examine the clinical relevance of antibodies
      detected in the sera of patients following renal transplantation. The sera from
      23 transplant recipients with acute rejection and 10 transplant recipients with
      diagnosed chronic rejection were tested against various epithelial, monocyte and
      endothelial cell lines (A549, HTB44, primary renal epithelial, U937 and Ea-hy
      926). The test used for detecting binding antibodies was a simple, indirect
      immunofluorescence flow cytometric technique. The level of IgG antibodies
      directed against the test cell lines was examined in the sera of patients with
      mild or severe rejection and compared to those of patients showing no signs of
      rejection. Patients with chronic rejection were found to have increased levels of
      antibodies (IgG and IgM) when compared to patients with either end-stage renal
      failure or patients with stable post-transplant renal function. Antibodies
      detected by the present technique were directed against antigens found on all
      cell lines tested, and immunoblotting indicated that they were directed against
      non-HLA antigens. In conclusion, monitoring for the presence of such antibodies
      may provide a valuable prognostic indicator of graft rejection in renal
      transplant patients.

PMID- 7626183
TI  - The quality of function of renal allografts is associated with donor age.
AB  - The quality of renal allograft function was assessed by prospective measurement
      of creatinine clearance at 1 year (n = 197) and at 3 years (n = 115) after
      cadaveric renal transplantation in a cohort of 268 patients treated with triple
      therapy immunosuppression. Donor age (P < 0.0012) and recipient age (P < 0.01)
      were independently associated with creatinine clearance both at 1 and at 3 years.
      In patients with donor age above 50 years and recipient age above 45 years, the
      mean creatinine clearance was 32.7 (SD 10.4) ml/min (n = 27). When the donor age
      was below 30 years and recipient age below 45 years, the mean creatinine
      clearance was 55.6 (SD 14.4) ml/min (n = 47, P < 0.001). However, in these
      patients there was no significant association between graft function and many of
      the factors known to influence graft survival, such as HLA matching,
      sensitisation of the recipient, and the occurrence of rejection. In conclusion,
      the quality of renal allograft function declined with increasing donor and
      recipient age in our patients, whilst immunological factors were not
      significantly associated with function in surviving grafts.

PMID- 7626184
TI  - The endothelium-derived relaxing factor-mediated acetylcholine response of the
      arterial perfusion pressure after cold storage of the isolated rabbit kidney.
AB  - The vasodilatation induced by acetylcholine (ACh) in a rabbit isolated perfused
      kidney was abolished when the tissue was exposed to cold ischemia for 72 h in
      Euro-Collins (EC) solution. This vasodilatation is due to the release of
      endothelium-derived relaxing factor (EDRF) from renal vasculature as evidenced by
      the attenuation following methylene blue pretreatment. When kidneys were
      preserved in EC solution containing UK 38485, a thromboxane synthase inhibitor,
      or nicardipine, a calcium channel blocker, ACh-induced vasodilatation persisted
      after 72 h of cold ischemia. These results were taken as evidence of tissue
      protective activity of UK 38485 and nicardipine and have promising implications
      for cadaveric kidney transplantation.

PMID- 7626185
TI  - Successful simultaneous transplantation of kidney and fetal pancreatic islet
      masses.
AB  - This paper reports our experience with the successful simultaneous
      transplantation of kidney and fetal pancreatic islets in 46-year-old diabetic
      man. No detectable C-peptide level was noted and the end-stage nephropathy
      required hemodialysis. The cadaver kidney and two masses of 8-week-cultured fetal
      islets were grafted simultaneously. After revascularization of the kidney, the
      islet masses were placed under the kidney capsule. Following transplantation,
      islet function was demonstrated by a higher C-peptide level, which subsequently
      persisted. Twenty-four months after grafting, islet function was provoked by
      glucagon and glucose, which led to elevations in the C-peptide and insulin
      levels. The insulin requirement fell from 58 to 24 U/day during the post
      transplant period of 24 months. The mean value of HbA1C (5.6% +/- 0.3%) indicated
      a constantly normal carbohydrate metabolism. Improvements in retinopathy were
      also noted. Three periods of kidney rejection were diagnosed, but these proved
      reversible with high-dose steroid treatment. The serum and urine beta-2
      microglobulin levels correlated well with rejection and recovery. More than 2
      years after grafting, kidney functions is in the normal range. On sonography, the
      transplanted islet masses were repeatedly clearly visible, and 24 months
      following transplantation the volume was twice the original one. The results
      indicate that simultaneous kidney and fetal pancreatic islet grafting is
      advantageous in end-stage nephropathy secondary to type I diabetes mellitus.

PMID- 7626186
TI  - Loss of speech after orthotopic liver transplantation.
AB  - Alteration of speech is a rare but distressing complication of orthotopic liver
      transplantation (OLT). We describe a characteristic speech disorder identified in
      a large series of consecutive patients undergoing OLT. Between 1988 and 1993, 525
      adults underwent OLT. For all recipients with neurologic complications, we
      reviewed clinical findings, imaging and electrophysiologic test results, and
      perioperative laboratory data. Five patients (ages 23-52; UNOS status 3-4)
      exhibited a characteristic pattern of stuttering dysarthria, leading to complete
      loss of speech production, occasionally with elements of aphasia. In four of the
      five patients, right-sided focal seizures were subsequently noted. All cases
      presented within the first 10 postoperative days and improved with 1 month of
      cessation of cyclosporin (CyA), although halting, monotonous speech was evident
      to some degree in all five for up to 1 year. There was no correlation between
      onset of symptoms and CyA levels. None of the patients has clinical or radiologic
      findings suggestive of central pontine myelinolysis or akinetic mutism. EEGs and
      Spect scan results were consistent with dysfunction in the left
      frontotemporoparietal regions of the brain. A characteristic speech disorder,
      which may be described as cortical dysarthria or speech apraxia, occurs in
      approximately 1% of adults undergoing OLT. Prompt recognition of this syndrome
      and temporary cessation of CyA therapy may favorable affect the course.

PMID- 7626187
TI  - Some contemporary ethical considerations related to organ transplantation.
AB  - With the increasing number of transplantable organs and tissues, as well as
      improvements in transplantation results, has come a severe shortage of organ
      donors. Consequently, new ethical dilemmas, related to the fair allocation of
      available organs and the use of alternative sources of donor organs, are of
      growing concern. Establishing fair allocation priorities is a serious problem in
      organ transplantation. Ethically, they should be defined by society as a whole
      rather than exclusively by the medical profession. Proposed solutions for the
      organ donor shortage, each with their unique ethical constraints, include the use
      of related donors, partial organ transplantation, cell transplantation using
      fetal tissue, and the use of animal organs "xenotransplantation ". Commercial
      trading in donor organs must be regarded as an unethical activity rather than an
      ethical dilemma since the donors are motivated by monetary rather than by
      humanitarian reasons. These ethical dilemmas could be largely avoided by an
      effective reduction in the severe shortage of postmortal organ donations.

PMID- 7626188
TI  - A technique for hepatic artery anastomosis during orthotopic liver
      transplantation.
AB  - Hepatic artery thrombosis remains the most common technical complication that
      causes graft failure following orthotopic liver transplantation. The Hepatic
      artery anastomosis should be performed using meticulous technique and adequate
      magnification. We report a very low incidence of Hepatic artery thrombosis (1.3%)
      utilising a modified microvascular 120 degrees triangulating technique in 150
      adult liver transplants.

PMID- 7626190
TI  - Delightful hair growth after lung transplantation.

PMID- 7626189
TI  - Chronic portosystemic hepatic encephalopathy refractory to medical treatment
      successfully reversed by liver transplantation.

PMID- 7626191
TI  - Cytokines and adhesion molecules in respiratory allergy.
AB  - Cytokines and adhesion molecules play a central role in the inflammatory process
      of respiratory allergy. Cytokines like IL4 acts on IgE synthesis and expression
      of low affinity CD23 IgE receptors, IL-5 on eosinophil differentiation and
      activation and IL-2 on T cell activation and on the expression of CD25 IL-2
      receptors. IL-2, IL-4 and IL-2 soluble receptor have been studied in pollen
      sensitive patients before, during and after pollen season. IL-2 serum levels
      initially increase and decrease at the end of allergen exposition. IL-4 serum
      level do not significantly changes during pollen season. Adhesion molecules are
      essential for recruitment and migration of inflammatory cells to tissues. CD45RO
      T memory cells expressing generally the adhesion molecule CD29 have also been
      studied in a group of pollen sensitive patients. During the peak of antigen
      exposition CD45RO/CD29 cells significantly decrease a turnover between CD45RA
      naive cells and memory cells being observed. The study of cytokines and adhesion
      molecules could add new data on the comprehension of inflammation in respiratory
      allergy.

PMID- 7626192
TI  - [Ocular Allergy Observatory. National epidemiological survey of seasonal allergic
      keratoconjunctivitis seen in ophthalmology].
AB  - The main objective of this first epidemiological ocular allergy survey was to
      precise the profile of patients with an ocular allergy, especially in terms of
      antecedents, clinical type and trigger or favourising factors, in order to better
      determine the evolution of the type of diagnosed allergy. This survey covered 399
      sufferers drown from amongst general ophthalmologists patients consulting for
      ocular allergy. Three main points which came out of the survey were: - the
      chronic aspect of this pathology and the multiplicity of responsible allergens; -
      the almost permanent existence of conjunctival lesions (9 patients out of 10) and
      corneal epithelial disease (1 patient out of 3); - the need for an extremely
      rigourous and thorough questioning of the patient and a complete ophthalmologic
      examination covering not only the symptoms but equally the lesions of ocular
      allergy.

PMID- 7626193
TI  - Pets, allergy and respiratory symptoms in children living in a desert country.
AB  - The aim of this paper was to study the effect of pets and other domestic animals
      effect on allergic respiratory symptoms among United Arab Emirates primary school
      children. A cross-sectional survey of 2200 school children living in both urban
      and rural areas was conducted using self-administered questionnaires between
      November 1993 and June 1994. The age range of the children studied was 6-12
      years, with a mean of 9.23 and standard deviation of 2.14 years; 51% were girls
      and 49% were boys. Pet ownership was defined by the presence of birds, cats,
      camels, dogs, goats, poultry and rabbits in the home. One thousand and thirty-six
      (1036/2090 = 49.6%) of the 2090 families studied had at least one animal at home.
      However, respiratory symptoms, pet allergy, chronic cough, chronic wheeze,
      breathlessness or chest tightness, doctor-diagnosed asthma, rhinitis and eczema
      was reported by 633 families (30.3%) from 2090 studied families. The highest
      prevalence of reported respiratory allergy and symptoms was found in children who
      had pets in the past and currently. The lowest prevalence of reported respiratory
      allergy and symptoms was found in children who never had pets in their lives.
      Past pets ownership was generally associated with a higher prevalence of pets
      allergy and respiratory symptoms. No less than 218 (10.4%) reported removing pets
      in the past because of an allergy or other health problems in the child or in
      other family members. The risk of having pet allergy in children with animals was
      found to be twice than that of children without (RR: 2.13; 95% CI: 1.53-2.97; p <
      0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7626194
TI  - [Cutaneous forms of lupus].

PMID- 7626195
TI  - [Local treatments in dermatology].

PMID- 7626196
TI  - [A very significant case of allergy to celery].

PMID- 7626197
TI  - Interaction between intercalation type anticancer drugs and DNA studied by
      ultraviolet resonance Raman spectroscopy.
AB  - The interaction of typical intercalation type anticancer drugs, adriamycin (ADM)
      and aclacinomycin (ACM), with calf thymus DNA was studied first with ultraviolet
      resonance Raman spectroscopy (UVRRS). The results demonstrate that the important
      information such as intercalation sites of drugs, the electronic interaction and
      the hydrogen bonds between drugs and DNA can be obtained by UVRRS. The method can
      also show the influence of drugs on DNA conformation and hydrogen bonds between
      bases of DNA.

PMID- 7626198
TI  - Analysis and PCR detection of antigen compositions of ovine progressive pneumonia
      virus.
AB  - Ovine progressive pneumonia virus (OPPV) was proliferated utilizing sheep foetal
      lung cells, and the cytopathic effect (CPE) of the virus was investigated. OPPV
      was purified with a 10%-sucrose cushion and then with 20%-55% discontinuous
      sucrose density gradient centrifugation. The structural proteins and antigen
      compositions of OPPV were analysed by SDS-PAGE and Western blotting. Besides, the
      OPP proviral cDNAs of the virus-infected cell cultures and the peripheral blood
      monocytes from sheep infected by the virus were detected using polymerase chain
      reaction (PCR). The results show that the CPE of sheep foetal lung cells infected
      by OPPV is typical of the disease. The purified virions are intact and of high
      purity when observed with an electron microscope. OPPV proteins consist of 18
      polypeptide bands and the molecular weights range from 18 to 120 kd. Among these,
      3 were glycoproteins (designated by gp120, gp50 and gp47). The appearance and
      peak time of the p28 antibody from sheep inoculated with OPPV are earlier than
      those of the p94 antibody to OPPV. Besides, the strength of immune reaction of
      p28 antibody is greater than that of p94 antibody. With PCR, it is demonstrated
      that the initial time for OPP proviral cDNAs to be integrated into the sheep
      foetal lung cells and the peripheral blood monocytes in sheep were 24 h and 9 d
      after inoculation, respectively.

PMID- 7626199
TI  - Abrupt reduction of c-myc expression by antisense RNA inducing terminal
      differentiation and apoptosis of a human esophageal cancer cell line.
AB  - A human esophageal cancer cell line (EC8712) expressing high-level Myc protein
      was infected with recombinant retroviral particles (pA-BD9) at a multiplicity of
      infection (MOI) 1:1. This viral particle contains a neomycin-resistant gene and a
      1.53-kb antisense RNA spanning the 2nd exon and its flanking sequences of the
      human c-myc oncogene. The G418-resistant EC8712 clones showed an 86% inhibition
      of growth rate and morphological changes characteristic of terminal
      differentiation and apoptosis. A decrease of about 80% of Myc protein was also
      observed in these infected cells by ABC-ELISA assay. 12-24 h after the infection
      of EC8712 cells with pA-BD9 at a high viral particle concentration (MOI = 1:10),
      the integration of the extrinsic 1.53-kb antisense c-myc fragment into the cancer
      cell genome was evidenced by the Southern blot analysis. Northern blot analyses
      showed the expression of this antisense fragment and a decrease of the intrinsic
      c-myc expression by 74% in comparison with that of the parental EC8712 cells.
      Heterotransplants of the infected EC8712 cells into the nude mice revealed a
      substantial decrease in tumorigenicity and morphological changes characteristic
      of terminal differentiation and apoptosis. Primary monolayer cell cultures of
      normal epithelia derived from the fetal and adult esophagus mucosa were set as
      controls. No noticeable increase in c-myc expression was found in these cultures.
      Infection of these cells with the same recombinant viral particles neither
      affected the growth rate of the cells nor their normal morphology. Our
      experiments indicate that the drastic decrease of the over-expressed Myc protein
      in cancer cells may also be an entrance to one of many pathways leading to the
      terminal differentiation and programmed cell death.

PMID- 7626201
TI  - Transmembrane Ca2+ gradient-mediated phosphatidylcholine modulating sarcoplasmic
      reticulum C(a2+)-ATPase.
AB  - The sarcoplasmic reticulum (SR) C(a2+)-ATPase was purified and reconstituted into
      the sealed phospholipids vesicles with or without transmembrane Ca2+ gradient.
      The role of phospholipids, especially phosphatidylcholine (PC), in the modulation
      of C(a2+)-ATPase by transmembrane Ca2+ gradient was investigated. The results are
      as follows. (i) Incubated with phospholipids, the enzyme activity of the
      delipidated C(a2+)-ATPase is inhibited by Ca2+ and the highest inhibition is
      observed in the presence of PC. (ii) When there exists a transmembrane Ca2+
      gradient (higher Ca2+ concentration inside vesicles, 1,000 mumol/L:50 mumol/L,
      similar to the physiological condition), the inhibition of C(a2+)-ATPase by
      transmembrane Ca2+ gradient can be only observed in the vesicles containing
      PC:PE, but not in those containing PS:PE or PG:PE. The highest inhibition is
      obtained at a 50:50 molar ratio of PC:PE (iii) By comparing the effects of PC
      differing in acyl chains, higher inhibition of C(a2+)-ATPase is observed in
      vesicles containing DPPC:PE and DOPC:PE, while no inhibition in DMPC:PE vesicles
      (iv) If the transmembrane Ca2+ gradient is in the inverse direction, the enzyme
      activity of C(a2+)-ATPase is inhibited whenever reconstituted with acidic or
      neutral phospholipids.

PMID- 7626200
TI  - Construction and high expression of retroviral vector with human clotting factor
      IX cDNA in vitro.
AB  - The construction of the high titer and highly expressed safety retroviral vector
      carrying human clotting factor IX cDNA is reported. Retroviral vectors LNCIX,
      LIXSN and LCIXSN, driven by hCMV, LTR and hCMV combined with LTR promoter
      respectively, were constructed, based on the retroviral vector LNL6, and
      transferred into packaging cell line PA317 with electroporation. Human clotting
      factor IX was detected in the cultured cells transduced with LNCIX and LIXSN but
      not in the cells transduced with LCIXSN. The viral titer of PA317/LNCIX was
      800,000 CFU per mL. With ELISA detection, it was found that the cells transduced
      with this vector can express human clotting factor IX at the level of 3.3
      micrograms per 10(6) cells in 24 h in human fibrosarcoma cells HT-1080 and 2.5
      micrograms per 10(6) cells in 24 h in hemophilia B patients' skin fibroblast HSF
      cells, and more than 80% of them were biologically active. The viral titer and
      expression of human FIX were increased, and the construction of retroviral vector
      backbone was improved and the safety was guaranteed as compared to those vectors
      used previously. These vectors may produce a sufficient quantity of factor IX
      proteins to cause the phenotypic modification for hemophilia B patients.

PMID- 7626202
TI  - Regulation of human clotting factor IX cDNA expression in transgenic mice.
AB  - To study the expression of human clotting factor IX cDNA in transgenic mice,
      which is an essential work on gene therapy for hemophilia B, 3 recombinant
      constructions containing different lengths of human clotting factor IX cDNA have
      been introduced into the cultured cells. All of the recombinant constructions
      were found to be expressed well in vitro. They were then microinjected into the
      male pronuclei of the fertilized mouse eggs respectively for generating
      transgenic mice. Unfortunately, none of them was expressed in any transgenic
      mice. These results show that the expression of the human clotting factor IX cDNA
      in the transgenic mice can be determined by cis regulatory element(s). As
      compared with the results from other related works, it is suggested that the cis
      regulatory element(s) is resided in the 5'-end non-coding region.

PMID- 7626203
TI  - [Effects of presoaking on the germination of licorice seeds].

PMID- 7626204
TI  - [Experimental comparison of the analgesic action of Aconitum and its processed
      products].
AB  - This paper deals with the effects of crude Aconitum and Aconitum processed by a
      new method of moistening and steaming, and by method of pharmacopoeial
      stipulation on the analgesic action with writhing test and hot plate test in
      mice. The result shows that the Aconitum processed by new method No 1, which
      applies moistening in water for 48h and then heating with high pressure steam
      (68.65kPa, 115 degrees C) for 2h has an advantage over that processed according
      to pharmacopoeial routine (P < 0.05).

PMID- 7626205
TI  - [Quality standards of effervescent granules for the treatment of cold pain].
AB  - Thin layer chromatography was performed to identify the ingredients of
      Effervescent Granules for arresting cold pain (Hantongding Paoteng Chongji). The
      limited doses of aconitine, granularity, moisture, acidity, sugar content, etc.
      were detected, and the contents of paeoniflorin, glycyrrhetinic acid and total
      alkaloids were determined. Thus, the quality standards for pharmaceutical
      preparation were preliminarily worked out.

PMID- 7626206
TI  - [A review of the processing of Euphorbia kansui Liou].

PMID- 7626208
TI  - [TLC scanning determination of baicalin content in niuhuang qingxin pills].
AB  - Baicalin in the samples was extracted with ultrasonic wave, the extract was
      spotted on thin-layer plates of gel GF254 and developed with the mobile phase
      consisting of toluene-ethylacetate-formic acid (2:3:2.2). Determinations were
      carried out with Shimadzu CS-930 TLC scanner with lambda s = 280 nm and lambda R
      = 207 nm. The linear range was 0.46-4.6 micrograms/ml. The average recovery of
      baicalin from the samples was 98.35%, RSD = 2.82%.

PMID- 7626207
TI  - [Research on rectal administration of bark of official Magnolia].
AB  - Fluorescence assay was applied to the determination of magnolol in rabbit blood,
      and the best way to administer the bark of official magnolia per rectal was
      established by orthogonal test. Then the two routes of administration were
      compared by AUC of magnolol and per rectal was found better than P.O. In
      addition, the modified isolated rectum-bag method was applied successfully to the
      research on rectal administration of bark of official magnolia.

PMID- 7626209
TI  - [Antidepressant active constituents in the roots of Morinda officinalis How].
AB  - Five compounds having antidepressant activities have been isolated from the roots
      of Morinda officinalis, a Chinese traditional Yang-tonic drug. These compounds
      were identified as succinic acid (1), nystose (2), 1F-fructofuranosylnystose (3),
      inulin-type hexasaccharide (4) and heptasaccharide (5) by chemical and
      spectroscopic methods. All of the compounds are isolated from the species of
      genus Morinda for the first time.

PMID- 7626210
TI  - [Two phthalide dimers from rhizome of Ligusticum sinense Oliv cv. chaxiong].

PMID- 7626211
TI  - [Immunopharmacological effects of polysaccharide from the stem of Actinidia
      arguta (Sieb. et Zucc.) eX Miq].

PMID- 7626212
TI  - [Protective effects of methanolic extract of Oenanthe stolonifera (Roxb.) Wall.
      ex DC. on myocardial injury induced by ischemia and reperfusion in rats].
AB  - The methanolic extract Oenanthe stoloni fera iv, pretreatment can significantly
      prevent the arrhythmias induced by myocardial ischemia and reduce the myocardial
      infarct size in rats. It can also markedly prevent myocardial ischemia and
      reperfusion-induced arrhythmias. In addition, the methanolic extract of Oenanthe
      stoloni fera (100 mg/kg i.v.) helps significantly to decrease the MDA content and
      preserve the SOD activity in plasma.

PMID- 7626213
TI  - [Effect of xiaopiling granules on muscular histochemistry of gastric precancerous
      changes in rats].
AB  - The effect of Xiaopiling Granules on muscular histochemistry of gastric
      precancerous changes in rats was observed quantitatively. The activity of SDH and
      M-ATPase as well as the content of muscular glycogen in model groups were found
      significantly lower than those of the normal groups (p < 0.01), and in this
      decrease Xiaopiling Granules had markedly played a preventive and therapeutic
      role.

PMID- 7626214
TI  - [Taxonomic studies on original plants of radix Euphorbiae ebracteolatae].
AB  - It has been discovered through investigation across the country that, thus far,
      the Radix Euphorbiae Ebracteolatae is derived from 12 species (varieties, forms)
      of 3 families. Their classification characters are discussed and a key is given
      in this paper.

PMID- 7626215
TI  - [Medicinal plant resources of Dendrobium in Sichuan Province].
AB  - Eleven species of Dendrobium grown in Sichuan Province were studied including
      their classifications and distributions. All of them are used as the merchandise
      Shihu. Among them, there are 3 species which are found in Sichuan for the first
      time and 2 new species whose medical effects are described here in. Problems
      about the exploitation, utilization, quality standards, etc. of these resources
      are preliminarily discussed. A key for the identification of all these 11 species
      has been compiled and presented.

PMID- 7626216
TI  - Cis-acting effects of sequences within 2.4-kb upstream of the human c-myc gene on
      autonomous plasmid replication in HeLa cells.
AB  - We have used density shift analysis to monitor the autonomous replicating
      sequence (ARS) activity of plasmids containing various DNA fragments from the 5'
      flanking region of the human c-myc gene. The ARS activity of certain of these
      plasmids implied that structures in the c-myc DNA could be recognized for the
      initiation of replication in the absence of chromosomal integration. The plasmid
      pNeo.Myc-2.4 contains 2.4 contains 2.4 kb of c-myc 5'-flanking DNA, and
      replicated semiconservatively as a circular extrachromosomal element. Deletion
      derivatives of pNeo.Myc-2.4 containing either of two nonoverlapping regions of c
      myc DNA semiconservatively incorporated bromodeoxyuridine into discrete
      populations of heavy-light supercoiled molecules to roughly the same extent as
      the chromosomal DNA in the same cultures. Some constructs displayed lower ARS
      activity, implying that distinct cis-acting sequences in the c-myc 5'-flanking
      DNA may independently affect DNA replication. The ARS activity of two separate c
      myc sequences suggests that replication initiation signals are redundant in the c
      myc origin. The smallest c-myc insert that displayed substantial ARS activity was
      930 bp long and contained three 10/11 matches to the yeast ARS consensus and
      several additional features found in eukaryotic replication origins.

PMID- 7626217
TI  - The EGR1 protein contains a discrete transcriptional regulatory domain whose
      deletion results in a truncated protein that blocks EGR1-induced transcription.
AB  - Egr-1 is a ubiquitous immediate-early gene whose expression is induced by a wide
      range of different stimuli. A requirement for egr-1 expression has been
      demonstrated in pathways leading to both proliferation and differentiation,
      suggesting that egr-1 is a critical intermediary in determining the long-term
      cellular response to a stimulus. To determine how egr-1 coordinates a cellular
      response to receptor-mediated stimulation, we have developed a transient
      cotransfection assay to map functional domains in the EGR1 protein. We localized
      an activation domain to a serine/threonine/proline-rich region between amino
      acids 174 and 270. Using this information, we designed a mutant that lacks this
      activation domain, but retains the DNA-binding domain. When cotransfected into
      fibroblasts with an EGR1-dependent reporter, this mutant inhibited the
      transcriptional activity of both endogenous EGR1, as well as exogenously
      expressed, wild-type EGR1 protein. These data demonstrate that the activation
      domain of EGR1 is critical for the activity of the protein, and that a mutant
      lacking this domain can dominantly inhibit wild-type EGR1 function.

PMID- 7626218
TI  - Association of histone H4 genes with the mammalian testis-specific H1t histone
      gene.
AB  - Mouse and human H4 genes associated with the testis-specific H1t gene were
      isolated from genomic libraries and were sequenced. The deduced amino acid
      sequences are identical to other mouse or human H4 histones, but the genes differ
      significantly in their nucleotide sequences. Both the human and the mouse genes
      are located on the same DNA strand compared with the H1t gene. In contrast to
      this identical transcriptional orientation of H1t and its neighboring H4 gene in
      mouse and man, an H4 gene with the opposite orientation has been described in the
      vicinity of the rat H1t gene. Northern blot analysis of RNA from testicular cells
      separated by centrifugal elutriation, S1 nuclease mapping, and reverse
      transcriptase polymerase chain reaction (RT-PCR) amplification show that both the
      murine and human H4 genes, like the H1t gene, are expressed in testicular cells,
      whereas the H4 genes, in contrast to the H1t gene, are expressed in nontesticular
      human and mouse cell culture cells.

PMID- 7626219
TI  - The human troponin I slow promoter directs slow fiber-specific expression in
      transgenic mice.
AB  - Troponin I (TnI) is a muscle-specific protein involved in the calcium-mediated
      contraction of striated muscle. Three TnI isoforms have been identified, each
      encoded by a separate gene and expressed in specific striated muscles in the
      adult. The slow isoform gene (TnIs) is transcriptionally regulated during
      skeletal muscle development such that its expression in the adult is restricted
      to muscle fibers innervated by a slow nerve. To delineate regions of this gene
      that are responsive to information imparted by the slow nerve, we generated
      transgenic mice carrying -4,200 to +12 bp of the human TnIs gene linked to the
      bacterial chloramphenicol acetyltransferase (CAT) coding region. By Northern blot
      analysis, we detected transgene transcripts only in muscles containing slow
      twitch fibers. CAT histochemical analysis revealed that expression of the
      transgene is restricted solely to slow-twitch fibers as characterized by type I
      myosin heavy-chain (MyHC) expression. Using regeneration as a model for neural
      influenced expression, we show that this gene construct also contains sequences
      necessary to respond to cues from the central nervous system.

PMID- 7626220
TI  - The nucleotide sequence, structure, and preliminary studies on the
      transcriptional regulation of the bovine alpha skeletal actin gene.
AB  - The promoters of mammalian striated muscle actin gene contain binding sites for a
      number of transcription factors. Examples are the CArG boxes, which bind a
      protein identical to or related to serum response factor (SRF), E boxes, which
      bind myogenic determination factors such as MyoD and myogenin, and -CCGCCC-
      motifs, which bind the transcription factor Sp1. To date, the only mammalian
      sequences isolated and analyzed are from rodent and human. We have now isolated
      and sequenced the bovine gene encoding alpha skeletal actin, including almost 3
      kb of 5'-flanking region. When compared to the human and rodent genes (the only
      ones previously cloned and for which 5'-flanking sequences to only approximately 
      750 are known), there was the expected conservation in the coding region. A
      comparison of the promoter regions indicated that the bovine gene has three CArG
      boxes in the 5'-flanking region in positions identical to those in other species.
      The bovine proximal promoter is unique from those of human and rodent in that it
      has only one E box in the vicinity of the TATA box, near -350, whereas the other
      mammals have three. Far upstream sequences reveal clusters of E boxes near -2,500
      and -1,500. A minimal promoter element, to -297, which has no E boxes, is
      sufficient to activate transcription in myotubes derived from rat L6 and mouse
      C2C12 myoblasts.

PMID- 7626221
TI  - In vivo reconstitution of highly active Candida maltosa cytochrome P450
      monooxygenase systems in inducible membranes of Saccharomyces cerevisiae.
AB  - To establish a system for functional characterization of individual Candida
      maltosa cytochrome P450 monooxygenases, the NADPH-cytochrome P450 reductase from
      this yeast species was co-expressed in Saccharomyces cerevisiae with each of the
      following cytochrome P450 forms; P450Cm1 (CYP52 A3), P450Cm2 (CYP52 A4), and
      P450AlK2A (CYP52 A5). For this purpose, a multicopy plasmid was constructed that
      contained two independent expression units controlled by the galactose-inducible
      GAL10 promoter. As shown by spectral and immunological methods, large amounts of
      the desired monooxygenase components could be simultaneously produced in the
      respective S. cerevisiae transformants. It was important, however, to adjust semi
      anaerobic cultivation conditions during induction by galactose to minimize a
      mutual impairment of cytochrome P450 and NADPH-cytochrome P450 reductase
      formation. Compared to the specific cellular content of the host-own enzyme, a 75
      to 100-fold overproduction of the reductase component was obtained resulting in
      P450/reductase molar ratios of about 1:3 in the microsomal fractions prepared
      from the co-expression strains. At the same time, the rates of cytochrome P450
      dependent lauric acid hydroxylation increased more than 10-fold, showing a proper
      reconstitution of the C. maltosa monooxygenase systems in S. cerevisiae. Using
      intact cells, an efficient biotransformation of lauric acid to omega
      hydroxylauric acid and dodecanedioic acid was found. S. cerevisiae cells
      coexpressing cytochrome P450 and NADPH-cytochrome P450 reductase were
      characterized by a marked proliferation of the endoplasmic reticulum.
      Immunoelectron microscopy revealed a colocalization of the monooxygenase
      components produced to these newly formed membrane structures.

PMID- 7626222
TI  - Identification of optimized target sequences for the GLI3 zinc finger protein.
AB  - GLI3 represents an important control gene for development and differentiation of
      several body structures. Reduction in gene dosage already leads to severe
      perturbation, especially of limb morphogenesis. The gene encodes a zinc finger
      protein that likely functions as a transcriptional modulator. Because the five
      zinc fingers should be capable of recognizing an extended stretch of genomic DNA,
      we sought to identify sequences bound by GLI3 that may facilitate the search for
      target genes acting downstream of GLI3. Starting from the nonamer DNA binding
      sequence of the highly related GLI protein, we employed an oligonucleotide
      selection protocol to determine an optimized binding sequence for the GLI3
      protein. The resulting sequence bound by the GLI3 zinc fingers consists of 16
      nucleotides and shows a high degree of similarity to sequences bound by the GLI
      and tra-1 proteins. Comparison with protein-DNA interactions in the known crystal
      structure of the GLI-DNA complex suggests relevant interactions of additional
      amino acids of GLI3 with its target site. The newly identified GLI3 target
      sequence should prove very useful for both the structural analysis of the protein
      DNA complex and the search for genes whose expression is subject to regulation by
      the GLI3 gene product.

PMID- 7626223
TI  - A sensitive lacZ-based expression vector for analyzing transcriptional control
      elements in eukaryotic cells.
AB  - We have developed a eukaryotic expression vector that provides a rapid and
      sensitive measure of transcriptional activity modulated by general and tissue
      specific regulatory motifs. The lacZ structural gene has been linked to the
      minimal promoter of the human liver/bone/kidney alkaline phosphatase gene. In
      addition, a trimerized cassette of the SV40 polyadenylation region has been
      placed 5' of this promoter to reduce plasmid-initiated transcripts extending
      through the lacZ gene that would contribute to background beta-galactosidase
      (beta-Gal) activity. By combining the weak promoter and the poly(A) cassette,
      only a very low level of lacZ activity is detected in the absence of additional
      regulatory sequences. Regulatory domains can be inserted into this vector via a
      unique Bam HI restriction site and their activity can be rapidly monitored in
      situ via a colorimetric 5-bromo-4-chloro-3-indolyl-beta-D-galactoside (X-Ga)
      staining protocol. Also, the activity of linked regulatory domains can be
      measured quantitatively by assaying beta-Gal levels in cell extracts. We show
      that derivatives of this vector can be used to monitor the activity of general
      and tissue-specific control elements and can be transactivated by a single
      transcription factor in cotransfection experiments.

PMID- 7626224
TI  - Protection against Mycoplasma pulmonis infection by genetic vaccination.
AB  - The induction of an immune response against a foreign protein usually requires
      purification of that protein, which is injected into animals. The isolation of
      pure protein is time consuming and costly. Recently, a technique called biolistic
      transformation (biological ballistic system) microparticle injection, gene gun,
      or particle bombardment was developed. The basic idea is that DNA or biological
      material coated onto heavy tungsten or gold particles is shot into target cells
      or animals. We have vaccinated mice by introducing the gene (Mycoplasma pulmonis
      DNA or a specific fragment) encoding a protein recognized by a protective
      monoclonal antibody directly into the skin or muscle of mice by two methods: (i)
      using a hand-held form of the biolistic system that can propel DNA-coated gold
      microprojectiles (2 micrograms of DNA) directly into the skin; (ii) using a
      conventional intramuscular injection of the DNA (100 micrograms) into quadricep
      muscles of transfected mice. HeLa cells were transfected in vitro by the gene gun
      or by the liposomal delivery system. Indirect immuno-fluorescent antibody (IFA)
      assay of culture cells indicated that both methods could be successful.
      Production of antibody and cell-mediated immunity against M.pulmonis were
      monitored by assaying serum IFA and enzyme-linked immunosorbent assay (ELISA),
      and delayed type hypersensitivity. In addition, macrophage migration inhibition
      and lymphocyte transformation to antigen in spleen cells were also tested. Both
      delivery systems induced humoral and cellular immunity, and vaccinated the mice
      against infection. Genetic immunization by using the gene gun saves time, money,
      and labor; moreover, this general method is also applicable to gene therapy.

PMID- 7626225
TI  - [Prescription habits of Peruvian doctors and factors influencing them].
AB  - A study to determine what sources of information influence the prescription
      habits of Peruvian physicians, how those habits are modified by experience, and
      how appropriate the prescribed drug treatment is for certain common ailments was
      carried out from September 1991 to December 1992. A questionnaire was
      administered to 800 physicians in two urban fringe areas of Lima and Chimbote. Of
      those doctors, 184 had established practices and 309 were recent graduates. The
      questionnaire asked what sources of information determined prescribing behavior,
      what medicines were and were not indispensable in outpatient clinical practice,
      and what drug treatments were appropriate for iron deficiency anemia and lower
      urinary tract infections in women. The answers showed that knowledge acquired in
      medical school had little influence on the prescribing habits of either group of
      doctors. More than two-thirds stated that their principal source of pharmacologic
      information was the scientific literature: 69.9% of the practicing physicians and
      79.9% of the recent graduates, with the difference between the groups being
      statistically significant (P < 0.01). The drugs that were indispensable in
      ambulatory practice were correctly identified by 28.8% of the physicians, while
      28.9% correctly answered the question on what groups of drugs should not be
      prescribed. The differences between the two groups were not significant. On the
      other hand, 60% of the established physicians and 52% of the recent graduates
      gave the right answers to the questions on treatment of iron deficiency anemia
      and urinary tract infection, and there was no significant difference between the
      two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7626226
TI  - [Relation between nutritional status of adolescent mothers and neonatal
      development].
AB  - Intrauterine growth retardation and low birthweight--factors that strongly
      influence the physical and mental development of a child--are in turn affected by
      the nutritional status of the mother during pregnancy and, to a certain extent,
      by her pregestational nutritional status. Pregnant adolescents constitute a high
      risk group for nutritional problems because their own bodies are still growing.
      In order to examine the correlation between several variables related to body
      composition and nutritional status in a group of pregnant adolescents and certain
      indicators of neonatal development, a prospective longitudinal study was carried
      out in Valdivia, Chile, from September 1988 to May 1992. The study cohort was
      made up of 184 pairs consisting of mothers under 17 years of age who had attended
      a prenatal monitoring program and their newborns. The following groups of
      variables were tested for correlation: indicators of maternal body composition
      before pregnancy (pregestational weight recorded by the mother, height measured
      during the first visit to the program, and body mass index [pregestational
      weight/(height upon entering the program)]; indicators of maternal body
      composition during pregnancy (weight and body mass index upon entering the
      program and before giving birth, weekly weight gain, and total weight gain); and
      indicators of neonatal development (weight and length at birth, gestational age,
      and cranial perimeter). The weight of the mother before giving birth was
      statistically significantly correlated with the gestational age, length, weight,
      and cranial perimeter of the newborn. The body mass index prior to giving birth
      was weakly correlated with the weight and length of the newborn, and a
      significant direct correlation was also observed between the weight of the
      pregnant adolescent upon entering the program and the weight of her child at
      birth. No correlation was found between the indicators of fetal development and
      those of maternal pregestational body composition or nutritional status. These
      results show that interventions conducive to a good increase in maternal weight
      during pregnancy will help prevent a bad neonatal prognosis.

PMID- 7626227
TI  - [Association of tuberculosis and HIV infection in Brazil].

PMID- 7626228
TI  - Quantum physics, organic chemistry and the material nature of mutation--60 years
      later.

PMID- 7626229
TI  - Pathological, physiological, and evolutionary aspects of short unstable DNA
      repeats in the human genome.
AB  - One of the salient features of the mammalian genome is the vast excess of DNA
      without obvious function, such as repetitive DNAs, spacers, and introns. In
      recent years, microsatellites, which include short triplet repeats (mostly CAGn
      and CGGn) and dinucleotide repeats (notably CAn) have gained widespread
      attention, along with minisatellites which consist of somewhat longer repeat
      units. Micro- and minisatellites, collectively called variable number tandem
      repeats (VNTRs), can be highly unstable and display an amazing degree of
      polymorphism. This property is exploited for gene mapping, for tumor diagnosis,
      and in forensic medicine. Undue expansion of gene-associated microsatellites is
      also responsible for some severe genetic diseases, such as fragile X syndrome.
      Most or all of these diseases are caused by expansion of CAG and CGG triplets.
      Within protein-coding regions these triplets usually code for polymers of
      glutamine, serine, alanine or proline. Physiologically, such amino acid repeats
      are often found in transcription factors and can increase or decrease their
      activity, depending on the repeat number. Alone or in conjunction with DNA
      methylation, such repeats may offer a unique opportunity for subtle, semi-stable
      modulation of gene activity. Also, at least in some plants and perhaps other
      organisms, a quasi-Lamarckian inheritance is mediated by repetitive DNA.
      Generally, repetitive DNA sequences, whether represented by short or by long DNA
      segments, may be beneficial for the evolution of a species.

PMID- 7626230
TI  - Threonyl-tRNA synthetase.
AB  - Threonine contributes to the solubility and reactivity of proteins by its hydroxy
      group as well as to the formation and stability of the hydrophobic core of
      proteins by its methyl group. One may assume that the use of this bifunctional
      and simply structured amino acid was established early in evolution. Whereas the
      catalytic pathway of threonine activation and transfer into protein does not
      deviate essentially from those catalyzed by other aminoacyl-tRNA synthetases, the
      enzyme specific for threonine exhibits several interesting individual properties:
      its biosynthesis is regulated by feedback mechanisms, it can be selectively
      inhibited (out of twenty aminoacyl-tRNA synthetases) by the antibiotic
      borrelidin, and it can be a target for autoantibodies, thus being involved in the
      course of autoimmune diseases. The enzyme has been isolated from more than ten
      organisms showing a dimeric nature and molecular masses between 110 and 220 kDa.
      Additionally, in several of these cases, the gene of threonyl-tRNA synthetase has
      been localized, cloned and sequenced, exhibiting proteins of 400 to 800 amino
      acids chain length. More interesting facts can be expected from future research
      ranging from chemistry and molecular biology to medicine, e.g. by elucidation of
      the three dimensional structures of threonyl-tRNA synthetases and of their
      antigenic epitopes, possibly followed by therapeutic use of less antigenic mutant
      proteins.

PMID- 7626231
TI  - Regulation of the activity of lysosomal cysteine proteinases by pH-induced
      inactivation and/or endogenous protein inhibitors, cystatins.
AB  - The kinetics of pH-induced inactivation of human cathepsins B and L was studied
      by conventional and stopped-flow methods. The inactivation of both enzymes was
      found to be an irreversible, first-order process. The inactivation rate constants
      increased exponentially with pH for both enzymes. From log kinac vs pH plots, 3.0
      and 1.7 protons were calculated to be desorbed for pH-induced inactivation of
      cathepsins L and B. Cathepsin B was thus substantially more stable than cathepsin
      L (approximately 15-fold at pH 7.0 and 37 degrees C). Cathepsin B was efficiently
      inhibited by cystatin C at pH 7.4, whereas the inhibition by stefin B and high
      molecular weight kininogen was only moderate. In contrast, cathepsin L was
      efficiently inhibited by both chicken cystatin and stefin B at this pH kass
      approximately 3.3 x 10(7) m-1 s-1).

PMID- 7626232
TI  - Affinity labelling of the catalytic and allosteric ATP binding sites on pyruvate
      kinase type I from Escherichia coli.
AB  - The allosterically regulated pyruvate kinase type I (PKI) from E. coli was
      inactivated by the ATP analog 2',3'-dialdehyde ATP (o-ATP) with a Ki of 3.6 mM.
      ATP and phosphoenolpyruvate protected the enzyme activity while the allosteric
      activator fructose 1,6-bisphosphate enhanced the rate of inactivation. Incubation
      with o-ATP, followed by reduction of the formed Schiff bases with radioactive
      sodium borohydride, was employed to determine the ATP binding sites of PKI. After
      tryptic digestion, the purification of the labelled peptides and the sequence
      analysis allowed to identify four modified lysyl residues, namely Lys173, Lys175,
      Lys272, and Lys317 of the known DNA-deduced sequence of PKI. The close lysines
      173 and 175 reacted with o-ATP in a mutually exclusive way and accounted together
      for 53% of the recovered radioactivity, the rest being distributed on Lys272
      (31%) and Lys317 (16%). When fitted on the available three-dimensional structure
      of muscle pyruvate kinase, the position of the modified lysines defines both the
      catalytic and the allosteric ATP binding sites on PKI.

PMID- 7626234
TI  - Human small intestinal sucrase-isomaltase: different binding patterns for malto-
      and isomaltooligosaccharides.
AB  - The hydrolysis of maltose and isomaltose and of sucrose and isomaltose at two
      different catalytic sites of sucrase-isomaltase has been demonstrated. Maltose
      and sucrose are competing for the same catalytic center. This competing can be
      described by alternative substrate kinetics. Steady-state kinetic parameters Km
      and k0 (maximal reaction velocity per mol enzyme) for linear alpha-1,4 and alpha
      1,6 glucosyloligosaccharides has been determined. Using these parameters subsite
      affinities for the catalytic sites of sucrase and isomaltase were computed. The
      different numbers of subsites for sucrase (2 subsites) and isomaltase (4
      subsites) indicate, that the binding patterns for maltooligosaccharides and
      isomaltooligosaccharides are different. That means that for sucrase unproductive
      enzyme-maltooligosaccharide complexes are definitely less probable than the
      productive one. As in human small intestinal glucoamylase-maltase in the
      isomaltase moiety four subsites can be evaluated with affinity values (Ai): A1 =
      2.6 (+/- 0.91), A2 = 13.8 (+/- 0.70), A3 = 1.1 (+/- 0.13) and A4 = 1.5 (+/- 0.13)
      kJ/mol using isomaltooligosaccharides. The two subsites of sucrase are evaluated
      to be A1 = 4.9 (+/- 0.70) and A2 = 16.7 (+/- 0.51) kJ/mol using
      maltooligosaccharides. The four subsite model for isomaltase and glucoamylase
      maltase is an indication that these two enzymes are mechanistically homologous in
      binding linear glucosyl-oligosaccharides.

PMID- 7626233
TI  - Interaction of non-aggregated boar AWN-1 and AQN-3 with phospholipid matrices. A
      model for coating of spermadhesins to the sperm surface.
AB  - Boar spermadhesins are 12-14 kDa lectins which coat the entire acrosomal cap
      sperm head surface. The large amount of spermadhesins AQN-1, AQN-2, AQN-3, and
      AWN-1 present on in vitro capacitated spermatozoa (approximately 7 x 10(6)
      molecules of each spermadhesin per cell) suggested that they may bind to major
      component(s) of the sperm surface. We have investigated both the aggregation
      state of spermadhesins in seminal plasma using gel filtration chromatography, and
      their ability to bind to the major phospholipids of the boar sperm plasma
      membrane, i.e. phosphorylcholine and phosphorylethanolamine. The bulk (90%) of
      spermadhesins AQN-3 and AWN-1 were eluted as aggregated proteins (Mr > 50,000)
      with the void volume of a Sephadex G-50 column; the remaining 10% of the total
      amount of seminal plasma AWN-1 and AQN-3 were recovered, together with the whole
      amount of AQN-1 and AQN-2, in a fraction containing low-molecular-mass proteins
      (Mr 16,000-30,000). None spermadhesin of either gel-filtration fraction bound to
      a phosphorylcholine affinity matrix. On the other hand, low-molecular-mass
      (monomeric or dimeric) AQN-3 and AWN-1 were the only spermadhesins retained in a
      phosphorylethanolamine affinity column. Both AQN-3 and AWN-1 purified from
      seminal plasma by reverse-phase HPLC retained their lipid-binding capability. In
      addition, immobilization of AQN-3 and AWN-1 onto a phosphorylethanolamine matrix
      did not interfere with the ability of the proteins to bind bovine glycoprotein
      PDC-109, indicating that the structural determinants for the binding lipid and
      carbohydrates lay on different structural domains.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7626235
TI  - The pro-region of human intestinal lactase-phlorizin hydrolase is enzymatically
      inactive towards lactose.
AB  - The pro-region of intestinal lactase-phlorizin hydrolase (LPH alpha) has been
      proposed to be important for the correct folding of pro-LPH and mature LPH (LPH
      beta). In this communication, analysis of the catalytic function of the LPH alpha
      pro-region is presented. Expression of a cDNA encoding LPH alpha in COS-1 cells
      reveals a polypeptide that does not hydrolyse lactose. Likewise, no lactase
      activity is detected in LPH alpha purified from trypsin-treated pro-LPH. Mixing
      of LPH alpha and LPH beta does not lead to the activation of the latter. We
      conclude that LPH alpha does not contribute to the lactase activity despite the
      strong homologies with mature LPH beta. LPH alpha may play an important role as
      an intra-molecular chaperone.

PMID- 7626236
TI  - Secondary structure in solution of the hydrophobic protein of soybean (HPS) as
      revealed by 1H NMR.
AB  - COSY, TOCSY and NOESY experiments have been used to assign sequentially the 1H
      500 MHz NMR spectra of the Hydrophobic Protein of Soybean (HPS). Spin systems
      identification combined with sequential assignment allowed to identify the proton
      resonances of this 80 residues protein. Analysis of medium range connectivities
      showed that its secondary structure involved four helical fragments similarly
      located as in the structure deduced from X-ray diffraction. This work set the
      basis for a further fine comparison between the crystal and the solution
      structures and a dynamical study of HPS in solution. In addition, search of
      secondary structure similarities showed that the global folding of HPS should be
      rather similar to that found for non specific Lipid Transfer Proteins (ns-LTP)
      from vegetal origin. Distributions of the helical fragments along the primary
      sequences of these two classes of proteins were compared.

PMID- 7626237
TI  - Thermal denaturation of bacterial and bovine dihydrofolate reductases and their
      complexes with NADPH, trimethoprim and methotrexate.
AB  - Scanning microcalorimetry was used for the study of thermal denaturation of
      E.coli and bovine liver dihydrofolate reductases (cDHFR and bDHFR, respectively)
      and their complexes with NADPH, trimethoprim (TMP) and methotrexate (MTX) at pH
      6.8. It was shown that the denaturation temperature of bDHFR is 7.2 degrees C
      less than that of cDHFR and that ionic strength is equally important for the
      thermostability and cooperativity of the denaturation process of the two
      proteins. Binding of antifolate compounds significantly stabilizes DHFR against
      heat denaturation. The stabilizing effect and the transition cooperativity depend
      on the nature of the inhibitor, the presence of NADPH and the origin of the
      enzyme. The dependence of calorimetric denaturation enthalpy (calculated per gram
      of protein) on denaturation temperature for DHFRs, their complexes with NADPH and
      binary/ternary complexes with TMP/MTX fits to the same straight line with the
      slope of 0.66 J/Kg. This relatively high value indicates an essential role of
      hydrophobic contacts in the stabilization of DHFR structure. The change of
      denaturation temperatures in binary complexes with MTX/TMP (in comparison with
      the free enzymes) is as much as 14.2 degrees C/8.5 degrees C and 13.3 degrees
      C/3.2 degrees C for cDHFR and bDHFR, respectively. The same change in ternary
      complexes with MTX/TMP is much more pronounced and equals to 21.9 degrees C/16.8
      degrees C and 29.0 degrees C/16.4 degrees C. The vast difference of binary and
      ternary complexes thermostability demonstrates the important role of cofactor in
      the stabilization of enzyme. Moving from binary to ternary systems causes a
      significant increase in denaturation temperatures, even when corresponding
      association constants do not change (cDHFR binary/ternary complexes with MTX) or
      increases very slightly (bDHFR binary/ternary complexes with TMP). In all other
      cases the increase of denaturation temperature for each protein in complex with
      ligands correlates with the association constant for the corresponding complex.

PMID- 7626238
TI  - Conformational energies of substrates and inhibitors for carboxypeptidase A:
      stereoelectronic effect.
AB  - Because of the complexity involved in binding of a ligand to an enzyme the
      conformational preference of the bound ligand has not been well understood yet.
      We have examined the conformational energies of ligands for carboxypeptidase A
      using ab initio calculations. Considering the large stereoelectronic effect of 4
      5 kcal/mol, the energetic preference of the unbound ligand conformers which
      arises from the stereoelectronic effect appears to play a significant role in
      determining the bound ligand conformations.

PMID- 7626239
TI  - Stability of Escherichia coli single-stranded DNA binding protein (EcoSSB)
AB  - Conformation and stability of EcoSSB, a single-stranded DNA binding protein
      encoded by Escherichia coli, were analyzed by circular dichroism and fluorescence
      measurements. From CD measurements at pH 7.5, EcoSSB can be classified as a
      protein with high alpha-helix and beta-sheet content. The hydrophobicity of the
      environment of the tryptophan residues of the native protein is only marginally
      increased in comparison to the unfolded protein. The GdnHCl induced unfolding
      curves measured by CD and fluorescence are coincident and sigmoidal and show a
      monophasic transition. The stability of EcoSSB is concentration dependent and the
      unfolding behavior can be described as a two-state transition from the folded
      tetrameter to unfolded monomers. The mean values of free energy of dissociation
      and unfolding delta GH2O mu are between 173 and 177 kJ.mol-1 and the mean half
      concentration c1/2 of GdnHCl of the transition curves are about 1.5 M and 1.7 M
      for protein concentrations of 0.1 mg.ml-1 and 0.5 mg.ml-1, respectively.

PMID- 7626240
TI  - Theoretical investigation of the molecular structure of the pi kappa DNA base
      pair.
AB  - The structure of the nonclassical pi kappa base pair (7-methyl-oxoformycin B. .
      .2,4-diaminopyrimidine) was studied at the ab initio Hartree-Fock (HF) and MP2
      levels using the 6-31G* and 6-31G** basis sets. The pi kappa base pair is bound
      by three parallel hydrogen bonds with the donor-acceptor-donor recognition
      pattern. Recently, these bases were proposed as an extension of the genetic
      alphabet from four to six letters (Piccirilli et al, Nature 343,33 (1990)). By
      the HF/6-31G* method with full geometry optimization we calculated the 12 degree
      propeller twist for the minimum energy structure of this complex. The linearity
      of hydrogen bonds is preserved in the twisted structure by virtue of the
      pyramidal arrangement of the kappa-base amino groups. The rings of both the pi
      and kappa molecules remain nearly planar. This nonplanar structure of the pi
      kappa base pair is only 0.1 kcal/mol more stable than the planar (Cs)
      conformation. The HF/6-31G* level gas-phase interaction energy of pi kappa (-13.5
      kcal/mol) calculated by us turned out to be nearly the same as the interaction
      energy obtained previously for the adenine-thymine base pair (-13.4 kcal/mol) at
      the same computational level. The inclusion of p-polarization functions on
      hydrogens, electron correlation effects (MP2/6-31G** level), and the correction
      for the basis set superposition error (BSSE) increase this energy to -14.0
      kcal/mol.

PMID- 7626241
TI  - Rigid-body motions of sub-units in DNA: a correlation analysis of a 200 ps
      molecular dynamics simulation.
AB  - A 200 ps molecular dynamics simulation of the B-form double stranded self
      complementary octanucleotide d(CTGATCAG) is analyzed in terms of correlated
      motions using the canonical analysis approach. Each nucleotide is decomposed in
      three sub-units corresponding to the base, the sugar ring and the backbone
      respectively. The correlation between the full dynamics of two sub-units was
      found to decrease as their mutual distance increases. The interpretation of the
      full dynamics of sub-units as the superimposition of rigid-body motions
      (translation and orientation) and deformation shows that the main source of
      correlation is rigid-body motions. Correlation between sub-units deformation is
      weak and practically vanishes for sub-units belonging to non-adjacent
      nucleotides. It is also shown that the correlation is much more important for sub
      units of the same strand than of opposite strands. We conclude that the internal
      dynamics of the octanucleotide may be well described by rigid-body motions, the
      sub-units deformation having only local influence whereas sub-units translation
      and rotation have repercussion to long distances. The results presented in this
      study suggest how the number of degrees of freedom may be reduced for simulating
      long-time dynamics of oligonucleotides.

PMID- 7626242
TI  - An elastic model for conformational transitions of spacer DNA in chromatin; first
      results.
AB  - We study the elastic stability of the trajectory of DNA in the solenoid model for
      the 30 nm chromatin fiber, as extended by McGhee et al. [J.D. McGhee, J.M.
      Nickol, G. Felsenfeld and D.C. Rau, Cell 33, 831-841 (1983)] to visualize both
      internucleosomal (spacer) DNA and DNA bound to the core histones. Actually, we
      idealize this trajectory by neglecting the shallow pitch of the solenoid. The DNA
      trajectory is then transversely wound on a torus, like a helix on a cylinder. We
      then neglect the shallow pitch of the transverse winding. We find that there is a
      threshold length for the elastic stability of a DNA segment in the resulting
      trajectory, even if the DNA is not allowed to straighten away from the torus
      surface. For most organisms the length of spacer DNA exceeds the threshold. This
      result does not imply that anything is wrong with the solenoid model, wherein two
      nucleosomal turns of DNA are stabilized by interaction with core and linker
      histones. The result does suggest, however, that if internucleosomal DNA follows
      a path similar to nucleosomal DNA, then this path would also have to be
      stabilized, possibly by interaction with linker histone. A second result of the
      analysis is that the extent of instability depends significantly on the location
      of the starting point of the DNA. If the DNA starts on the outside of the torus,
      it is less unstable than if it starts on the inside. In the extended solenoid
      model, some turns of internucleosomal DNA are on the outside of the solenoid,
      some on the inside. This result thus suggests the possibility that localized
      structural disruptions are more likely for some nucleosome neighboring pairs than
      others. Of intrinsic theoretical interest is the reduction of the problem through
      a series of approximations to the solution of Mathieu's equation.

PMID- 7626243
TI  - DNA curvature of the tobacco GRS repetitive sequence family and its relation to
      nucleosome positioning.
AB  - Recently, a highly repetitive DNA sequence family (GRS) from tobacco was
      described in our laboratory. These sequences were found to be localized
      predominantly in the pericentromeric heterochromatin of tobacco chromosomes. To
      test the hypothesis that these sequences play an important role in the formation
      of heterochromatin, we investigated the DNA curvature of the GRS sequences and
      its possible impact to the chromatin structure at these loci. Application of the
      nearest-neighbour wedge model of intrinsic DNA curvature for the GRS1 family
      member predicted two loci of curvature: a major bend at the 5' end of the
      sequence and a minor bend of opposite direction at the centre of the GRS1. The
      presence of the major and the minor loci of DNA curvature was studied
      experimentally using permutation analysis and site-directed mutagenesis. The
      experimental results were consistent with the computer predictions. We gave
      evidence that the described DNA curvature is also present in the entire GRS
      family. Genomic statistical sequencing showed the conservation of the major bend
      sequence determinants in the members of the GRS family. To investigate the
      chromatin structure at the GRS sequences, we determined the nucleosome
      positioning in vivo at these sequences using thermal cycle primer extension. A
      relation between the curvature pattern and the histone octamer position was
      observed: the major bend is excluded from the nucleosome surface to the linker
      region, while the minor bend is distributed along the core DNA. The suggestion is
      made that the sequences in the minor locus of curvature define the rotational
      setting of the nucleosome, and a possible role of the major bend as a factor,
      which defines the translational setting, is discussed.

PMID- 7626244
TI  - Interaction specificity of benzimidazol group compounds with AT-containing
      polynucleotides.
AB  - The interaction between polynucleotides: poly(dA)-poly(dT), poly(dA-dT),
      poly(am2dA-dT), and the AT-specific compounds of benzimidazol group has been
      studied. It is been shown that these compounds bind to poly(dA)-poly(dT) and
      poly(dA-dT) at low and high salt concentration in solution. Poly(am2dA-dT)
      interacts with AT-specific compounds only at low salt, where this polynucleotide
      is in a B-form, but not at high salt, when the polynucleotide converts to another
      conformation. Thus, the interaction specificity of the groove-binding ligands is
      influenced not only by the minor groove substituents, but the peculiarities of
      the secondary structure of polynucleotides.

PMID- 7626245
TI  - Interaction of an amphiphilic peptide with a phospholipid bilayer surface by
      molecular dynamics simulation study.
AB  - Corticotropin-releasing factor (CRF) is the principal neuroregulator of
      adrenocorticotropic hormone (ACTH) secretion. Previous experiments have
      demonstrated that CRF binds avidly to the surface of single egg
      phosphatidylcholine vesicles and its amphiphilic secondary structure might play
      an important role in the function. In this study, the interaction of the residues
      13-41 in human CRF with the surface of a DOPC bilayer was investigated by
      molecular dynamics (MD) simulation in order to understand the role of the
      membrane surface in the formation of the amphiphilic alpha helix as well as to
      determine the effects of the peptide on the lipid bilayer. The model used
      included 60 DOPC molecules, 1 helical peptide (CRF13-41) on the bilayer surface,
      and explicit waters of solvation in the lipid polar head group regions, together
      with constant-volume periodic boundary conditions in three dimensions. The MD
      simulation was carried out for 510 ps. In addition, CRF13-41, initially in a
      helical form, was simulated in vacuo as a control. The results indicate that
      while it was completely unstable in vacuo, the peptide helical form was generally
      maintained on the bilayer surface, but with distortions near the terminal ends.
      The peptide was confined to the bilayer headgroup/water region, similar to that
      reported from neutron diffraction measurement of tripeptides bound to the
      phosphatidylcholine bilayer surface (Ref 1). The amphiphilicity of the peptide
      matched that of the bilayer headgroup environment, with the hydrophilic side
      oriented toward water and the hydrophobic side making contact with the bilayer
      hydrocarbon core. These results support the hypothesis that the amphiphilic
      environment of a membrane surface is important in the induction of peptide
      amphiphilic alpha-helical secondary structure. Two major effects of the peptide
      on the lipids were found: the first CH2 segment in the lipid chains was
      significantly disordered and the lipid headgroup distribution was broadened
      towards the water region.

PMID- 7626246
TI  - Molecular modeling studies on amphotericin B and its complex with phospholipid.

PMID- 7626247
TI  - Detailed assessment of spatial hydrophobic and electrostatic properties of 2D NMR
      derived models of neurotoxin II.
AB  - 2D NMR-derived spatial structures of neurotoxin II (NtII) and several homologous
      toxins in solution were assessed by comparison with their own amino acid
      sequences using a three-dimensional (3D) profile method. 3D profiles of all the
      toxin models match the sequences well and, therefore, the method of 3D profile
      was demonstrated to work correctly for these well-resolved NMR structures in
      aqueous solution. At the same time, the profile window plots reveal low scores in
      the bottom tip of loop II (residues 22-34 in NtII) and in beta-strand of loop III
      (residues 49-52). Some residues in the first poor-scoring region are of
      functional importance being involved in binding with nicotinic acetylcholine
      receptor (AChR). Furthermore, the second segment participates in intermolecular
      hydrogen bonding upon dimerization of postsynaptic neurotoxins in solution
      resulting in increasing of the 3D-1D score for residues at the interface between
      monomers. Therefore, the 3D profile method can be useful for detection
      functionally-important regions in well-resolved protein structures.

PMID- 7626248
TI  - Two-dimensional 1H NMR study of a tetradecapeptide with the consensus sequence
      Arg5-Asp-Val-Arg-Gly9: structural effects of the outside substitution Ser12 by
      Ala12.
AB  - Conformation of a tetradecapeptide with a RXVRG consensus sequence, Arg5-Asp-Val
      Arg-Gly9, found in several precursors of antibacterian peptides, was investigated
      in dimethylsulfoxide solution by proton NMR spectroscopy. Complete resonance
      assignments and conformational parameters were obtained through correlated (COSY)
      and nuclear Overhauser (NOESY) techniques. The 3J(alpha H, beta H) coupling
      constants and the intramolecular NOE, NH...beta H, were used to analyse the
      conformers around the C alpha-C beta bond and, in four cases, to obtain
      stereospecific assignments. Use of restraints derived from NOE connectivities and
      3J(NH, alpha H) coupling constants allows the determination of a range of phi and
      psi dihedral angles for all the residues in the sequence. The present NMR results
      provide favourable evidence for the formation of two bends in the consensus
      sequence of the tetradecapeptide. The first one has most of the features of a
      Glu4-Val7 beta-turn (low temperature coefficient of the Val7NH chemical shift,
      Arg5 alpha H...Val7NH and Asp6NH...Val7NH NOE correlations). The second one
      exhibits only the Asp6 alpha H...Arg7NH and Val7NH...Arg8NH NOE interactions.
      These consensus sequence organizations proposed were confirmed by molecular
      modeling based on low potential energy structure on the [4-9] fragment with high
      agreement of NOE data. Overall, the substitution of Ser12 by Ala12 shifts the
      conformation of the hydrophobic moiety [10-14] towards a quite random coil
      structure in this fragment and strongly destabilizes the folded structures of the
      consensus domain where only one NH (Val7) is solvent-shielded opposed to three
      (Asp6 to Arg8) in the [Ser12] tetradecapeptide. These conformational changes
      could be related to the processing enzyme activities on these model
      oligopeptides.

PMID- 7626249
TI  - Teaching transcultural nursing in undergraduate and graduate programs.

PMID- 7626250
TI  - Teaching transcultural nursing to transform nursing for the 21st century.

PMID- 7626251
TI  - Multiculturalism and transcultural nursing in Australia.
AB  - The author looks at Australia's multicultural society and identifies the failure
      of the nursing profession to provide nursing services that meet the commitment of
      Australia to preserve the cultural backgrounds and meet the needs of the people
      nurses serve. The author suggests ways in which this problem can be addressed. It
      is argued that there is a need to ensure that transcultural nursing services are
      recognized and made accessible to people from diverse cultural backgrounds.
      Nurses need educational preparation to provide them with the knowledge, skills,
      and attitudes essential to work with people from different cultures. Moreover,
      the cultural profile of the nursing profession should approximate those served.
      Nurses today must recognize these critical needs and be committed to provide
      transcultural nursing care that is so essential in Australia's multicultural
      society.

PMID- 7626253
TI  - Transcultural nursing: transforming the curriculum.
AB  - More than three decades have passed since Leininger established the field of
      transcultural nursing as a research based specialty which is recognized around
      the world as an essential and formal area of study and practice. When the
      importance of culture to nursing was first articulated by Leininger in the early
      1950s, knowledge and awareness of these cultural influences were largely unknown
      and unrecognized in nursing education. The typical 1950s nursing curricula were
      soundly rooted in biophysical medical content, technical skills, tasks, and
      practices with no mention of cultural influences. Few nursing faculty had formal
      academic preparation in the social sciences, and Leininger was the first
      professional nurse with doctoral preparation in anthropology.

PMID- 7626252
TI  - Feeding and weaning practices of Cuban and Haitian immigrant mothers.
AB  - The decline of breast feeding among immigrant mothers is of concern to
      transcultural nurses and other health care professionals. A descriptive survey of
      30 Cuban and 30 Haitian immigrant mothers in South Florida explored their feeding
      and weaning beliefs and practices. Findings revealed that social, economic, and
      political factors in their country of origin and in South Florida affected their
      traditional health-culture beliefs and practices related to breast and bottle
      feeding and weaning, initial fluid intake, introduction of supplemental foods,
      and administration of vitamins, minerals, and medications. Implications for
      transcultural nursing care are presented.

PMID- 7626254
TI  - President's message: culturally competent nursing care.

PMID- 7626255
TI  - Clinical incident #9. An African American woman in early labor.

PMID- 7626256
TI  - Information on certification and recertification.

PMID- 7626257
TI  - Patients achieve accurate home blood pressure measurement following instruction.
AB  - This study evaluates the effects of an instruction program conducted by
      registered nurses on subjects' ability to achieve three blood pressure
      measurements that were within 2 mmHg of simultaneous readings taken by an
      instructor listening through a dual headed stethoscope. The sample comprised 30
      subjects aged between 22 and 76 years who were referred to a Hypertension Unit
      over a two month period for home blood pressure instruction. After approximately
      45 minutes of individual instruction and practice in the use of an aneroid home
      blood pressure machine, subjects' ability to measure their blood pressure was
      assessed by the accuracy of their readings, their responses to a multiple choice
      knowledge questionnaire, their self-reported confidence in their ability to
      measure their blood pressure at home and an instructor's evaluation of their
      technique. Twenty seven percent of subjects achieved three measurements that were
      the same as those of their instructor, 57% and 17% obtained readings that were
      within 2 mmHg and 4 mmHg of an instructor respectively. Ninety percent of
      subjects obtained perfect scores in the knowledge questionnaire, 93% obtained
      perfect scores in the technique competency checklist and 100% of subjects either
      strongly agreed or agreed with the statement 'I feel confident enough to measure
      my blood pressure at home'. The study demonstrates that patients can be taught to
      accurately measure their blood pressure at home and, herefore, to provide
      reliable data to assist in the diagnosis and treatment of hypertension and
      hypotension.

PMID- 7626258
TI  - Home parenteral nutrition: the Royal Prince Alfred Hospital experience.
AB  - This paper reviews the outcomes for 14 patients treated with long-term home
      parenteral nutrition at the Royal Prince Alfred Hospital between 1978 and 1994.
      Prior to the introduction of home parenteral nutrition, all patients were unable
      to maintain adequate nutrition by enteral means and all had experienced repeated
      and/or long term admissions to hospital for total parenteral nutrition. The
      median time patients had been on home parenteral nutrition was 468 days (range 7
      days to 5,352 days) and seven patients were on home parenteral nutrition at the
      time of the review. The majority of patients were able to resume a reasonable
      place in society for varying periods and four of the patients returned to work.
      The conclusion from the Royal Prince Alfred experience is that home parenteral
      nutrition is a cost-effective method of maintaining nutrition in selected
      patients with chronic intestinal failure.

PMID- 7626259
TI  - Expanding the role of the clinical nurse consultant.
AB  - This paper describes the phases that were experienced by clinical nurse
      consultants during a role transition from ward-based experts to facility-oriented
      resource people. The six prerequisites that the consultants identified as
      required for successful transition from the ward-based to the facility-oriented
      role are discussed. The increased productivity of the CNCs is summarised and
      recommendations for further action are identified.

PMID- 7626260
TI  - Euthanasia: what do you think?

PMID- 7626261
TI  - An acute pain service: a quality assurance survey of nurses and doctors.
AB  - An acute postoperative pain service managed by the anaesthetic department of a
      metropolitan teaching hospital is described and the results of a quality
      assurance questionnaire survey of 116 nurses and 60 doctors are reported. Since
      its inception in 1990, the service has managed the postoperative pain of 1787
      patients with patient controlled analgesia and epidural and other regional
      analgesia. The study found that 97% of nurses and 92% of doctors believed that
      patients whose pain is well managed have fewer postoperative complications and
      shorter hospital stays than patients whose pain is not well managed. Both nurses
      and doctors who had experienced the pain service supported the increased use of
      patient controlled analgesia pumps and neither group believed that the acute pain
      service interfered with their management of patients.

PMID- 7626262
TI  - Conversations with researchers. Interview by Natalie Newman.

PMID- 7626263
TI  - Spiritual care: what does it mean to RNs?
AB  - The purpose of this descriptive study was to discover the meanings that two
      groups of registered nurses ascribed to the word 'spirit' and its derivatives.
      The study also examined the nurses' perceptions of the nature of spiritual
      nursing, the status of spiritual care in relation to 'normal' nursing care and
      the adequacy of nursing education as preparation for providing spiritual care.
      Data were gathered from audio-taped interviews with 10 registered nurses who
      worked in one hospice and 10 who worked in a variety of acute care settings. The
      participants were asked four open-ended questions and from their responses 29
      themes emerged which led to the construction of a model which shows that the
      nurses delivering spiritual care are influenced by their practice settings and
      nursing education which together impact on the quality of spiritual care. The
      elements of the model are discussed and recommendations that flow from the
      findings are made.

PMID- 7626264
TI  - Rapid protease screening using ammonium sulfate precipitations and a high
      performance centrifuge.

PMID- 7626265
TI  - Analysis of structure of sugar-beet pectin by enzymatic methods.
AB  - The structure of alkali-soluble pectin (ASP) prepared from sugar-beet pulp was
      determined. ASP was sequentially degraded by pure galactanase,
      rhamnogalacturonase and arabinosidase and sugar compositions and NMR analysis of
      the products used to assign the following tentative structure to ASP: a backbone
      based on units of -->4)-alpha-D-GalpA-(1--> 2)-alpha-L-Rhap-(1-->, and side
      chains both of arabinan and of arabinogalactan.

PMID- 7626266
TI  - Iridoid glucosides from the leaves and stems of Duranta erecta.
AB  - From the leaves of Duranta erecta, four new iridoid glucosides, duranterectosides
      A, B, C and D, were isolated along with durantosides I and II, lamiide,
      lamiidoside and verbascoside. Duranterectoside A was also isolated from the stems
      together with durantosides I, II and III, and lamiidoside. The structures of the
      new compounds were elucidated based on the spectroscopic evidence.

PMID- 7626267
TI  - Medicagenic acid saponins from Aster batangensis.
AB  - Two new medicagenic acid saponins, named asterbatanoside J and K, were isolated
      from the roots of Aster batangensis. On the basis of chemical and spectral
      studies especially 2D NMR including COSY, HETCOR, HMQC, HOHAHA, TOCSY, ROESY and
      HMBC techniques, their structures were established as 3-O-beta-D-glucopyranosyl
      (1--> 6)-beta-D-glucopyranosyl-2 beta, 3 beta-dihydroxy-olean-12-en-23 alpha, 28
      dioic acid- 28-O-alpha-L-arabinopyranosyl-(1-->3)-alpha-L- rhamnopyranosyl-(1-
      >2)-beta-D-fucopyranoside and 3-O-beta-D-glucopyranosyl-(1-->6)-beta-D
      glucopyranosyl- medicagenic acid-28-O-beta-D-xylopyranosyl-(-->4)-[alpha-L-
      arabinopyranosyl-(1 -->3)-alpha-L-rhamnopyranosyl-(1-->2) -beta-D-fucopyranside,
      respectively.

PMID- 7626268
TI  - Patensin, a saponin from Pulsatilla patens var. multifida.
AB  - Patensin, a new triterpenoid glycoside, was isolated from the ethanolic
      extraction of the roots of Pulsatilla patens var. multifida. Its structure was
      established as hederagenin 3-O-beta-D-galactopyranosyl-(1-->2)-beta-D-
      glucopyranoside on the basis of hydrolysis and spectral evidence including 1D and
      2D NMR techniques.

PMID- 7626269
TI  - Effects of denervation on antioxidant enzymes in nerve and muscles of rats.

PMID- 7626270
TI  - Enzymatic hydrolysis of DNA using a membrane bioreactor.
AB  - Aim of this work was a kinetic study of the deoxyribonuclease I (E.C. 3.1.21.1.)
      reaction in several conditions. Optimal reaction conditions with enzyme free in
      solution were determined. DNase activity was studied as function of several
      parameters such as pH, enzyme concentration, substrate concentration, cofactor
      concentration. The Km value of the free enzyme was also determined. Subsequently,
      the possibility to carry out the reaction in systems in which the enzyme was
      immobilized on the inner surface of the polymeric membranes was evaluated and
      realized. Experimental procedures, in these new conditions, permitted to
      determine the mass of immobilized enzyme and the percentage of the reaction
      product recovery. Results showed that the immobilization procedure determines a
      decay of the initial activity of enzyme, but there is an important increase of
      enzyme stability.

PMID- 7626271
TI  - Morphological features of blood circulation in the guinea pig lung.
AB  - The morphology of the lobar artery branches of the guinea pig lung was examined
      by optical microscopy and by the scanning electron microscope. Our results
      demonstrate that these branches consistently present a "rosary-like" structure
      that had been previously observed only occasionally in specimens of various
      organs from different animals. The function of these "bead-like" structures seems
      to be that of a control system of the blood flow to the lung alveoli, rather than
      that of a "pumping heart", as postulated previously by other authors.

PMID- 7626272
TI  - Erythrocyte-mediated toxification of 1,8-dinitropyrene: I. Reduction.
AB  - Nitroarenes are environmental contaminants produced during incomplete combustion
      processes. It has been reported that nitroreduction, the most important pathway
      of nitroarene toxification, occurs mainly in the liver and intestine. In the
      present study we have shown that red cells also possess the metabolic competence
      to reduce nitroarenes. In particular, 1,8-dinitropyrene, the nitroarene chosen as
      model compound, was reduced to the corresponding mono- and diamino-derivatives, 1
      amino-8-nitropyrene and 1,8-diaminopyrene, by human lysate supplemented with
      cofactors.

PMID- 7626273
TI  - Erythrocyte-mediated toxification of 1,8-dinitropyrene. II. Covalent bind to
      erythrocyte-proteins.
AB  - In the present study we have shown that erythrocyte-catalyzed 1,8-dinitropyrene
      reduction occurs via formation of reactive intermediate species, which bind
      covalently to haemoglobin and other erythrocyte proteins. In fact after mild-acid
      hydrolysis of lysate proteins exposed to DNP, the reduced metabolites, 1-amino-8
      nitropyrene and 1,8-diaminopyrene, were released, thus indicating the formation
      of sulphinamide adducts to proteins. These results suggest that haemoglobin
      adduct biomonitoring would be a useful method of controlling exposure to
      nitroarene in persons at risk.

PMID- 7626274
TI  - Natriuretic peptides binding sites in the vertebrate heart.

PMID- 7626275
TI  - Comparison of two methods for the recognition of guanine and cytosine rich
      regions on human gene sequences.
AB  - The authors compared two methods to recognise cytosine and guanine rich zones on
      19 DNA sequences. The computer method based on an artificial neural network
      algorithm indicated presence of guanine and cytosine rich regions also in genes
      not previously known to contain CpG islands.

PMID- 7626276
TI  - Contemporary trends in neurometric waveform analysis: introduction.

PMID- 7626278
TI  - EP component identification and measurement by principal components analysis.
AB  - Between the acquisition of Evoked Potential (EP) data and their interpretation
      lies a major problem: What to measure? An approach to this kind of problem is
      outlined here in terms of Principal Components Analysis (PCA). An important
      second theme is that experimental manipulation is important to functional
      interpretation. It would be desirable to have a system of EP measurement with the
      following characteristics: (1) represent the data in a concise, parsimonous way;
      (2) determine EP components from the data without assuming in advance any
      particular waveforms for the components; (3) extract components which are
      independent of each other; (4) measure the amounts (contributions) of various
      components in observed EPs; (5) use measures that have greater reliability than
      measures at any single time point or peak; and (6) identify and measure
      components that overlap in time. PCA has these desirable characteristics.
      Simulations are illustrated. PCA's beauty also has some warts that are discussed.
      In addition to discussing the usual two-mode model of PCA, an extension of PCA to
      a three-mode model is described that provides separate parameters for (1)
      waveforms over time, (2) coefficients for spatial distribution, and (3) scores
      telling the amount of each component in each EP. PCA is compared with more
      traditional approaches. Some biophysical considerations are briefly discussed.
      Choices to be made in applying PCA are considered. Other issues include
      misallocation of variance, overlapping components, validation, and latency
      changes.

PMID- 7626277
TI  - Cerebral source localization paradigms: spatiotemporal source modeling.
AB  - Spatiotemporal source modeling (STSM) attempts to interpret multichannel scalp
      recordings in terms of their contributing brain areas. Localization accuracy is
      generally limited by spatially correlated residual noise and by modeling
      simplifications. For signals emanating simultaneously from several sources,
      however, correct interpretation of the source structure is the prime concern. The
      discussion of various STSM methods emphasizes this validity issue. Methods are
      proposed for systematic search of alternate source models also consistent with
      the data, in order to prevent unwarranted conclusions, and for combining
      information from different montages and from data variability across trials to
      impose severe objective criteria for consistency of a source model with the data.

PMID- 7626279
TI  - An artificial neural network approach to ERP classification.
AB  - Artificial neural network-based approaches were developed to classify event
      related potential (ERP) waveforms. The networks utilized scalp-recorded ERP
      returns from six electrode sites. These ERPs were evoked as one individual
      responded to a series of auditorily presented object names while viewing various
      objects on a computer screen. The ERPs at the electrode sites were classified as
      a match decision or a no-match decision. A three-layer backpropagation neural
      network model was selected to formulate a global and a local classification
      approach. The backpropagation network in the global approach was designed to
      operate on a single ERP response which was the average of the ERP responses
      generated at the six electrode sites. The local ERP classification system
      consisted of six three-layer backpropagation networks. Each network was designed
      to operate on the ERPs generated at a single electrode site. A small data base
      consisting of eight match and eight no-match ERP responses was used to train and
      test the networks in a variety of ways. The results obtained clearly show that
      the neural network-based classifiers are able to discriminate with a high degree
      of accuracy between match and no-match conditions in ERP waveforms.

PMID- 7626280
TI  - An introduction to magnetoencephalography with some applications.
AB  - In this paper an attempt was made to describe the basic principles and procedures
      involved in recording, noninvasively, magnetic fields from the surface of the
      head and estimating the intracranial sources that give rise to these fields,
      presumably the same ones that result in time-varying voltages in the scalp that
      are known as Evoked and Event-Related Potentials. In addition, data from four
      experiments are briefly described as a means of providing concrete examples of
      the applicability of Magnetoencephalographic procedures to research issues of
      interest to cognitive neuroscientists.

PMID- 7626281
TI  - Measuring "chaos" in the brain: a tutorial review of EEG dimension estimation.
AB  - The technique of dimension estimation is currently a leading application of
      nonlinear dynamics (popularly termed "chaos theory") to EEG analysis. A tutorial
      review of this technique is presented along with some elementary background
      concepts from nonlinear dynamics. Practical aspects of applying dimension
      estimation to EEG data are also reviewed, and the possible role of deterministic
      chaos in brain function is discussed.

PMID- 7626282
TI  - Multiresolution analysis of event-related potentials by wavelet decomposition.
AB  - Wavelet analysis is presented as a new tool for analyzing event-related
      potentials (ERPs). The wavelet transform expands ERPs into a time-scale
      representation, which allows the analyst to zoom in on the small scale, fine
      structure details of an ERP or zoom out to examine the large scale, global
      waveshape. The time-scale representation is closely related to the more familiar
      time-frequency representation used in spectrograms of time-varying signals.
      However, time-scale representations have special properties that make them
      attractive for many ERP applications. In particular, time-scale representations
      permit theoretically unlimited time resolution for the detection of short-lived
      peaks and permit a flexible choice of wavelet basis functions for analyzing
      different types of ERPs. Generally, time-scale representations offer a formal
      basis for designing new, specialized filters for various ERP applications. Among
      recently explored applications of wavelet analysis to ERPs are (a) the precise
      identification of the time of occurrence of overlapping peaks in the auditory
      brainstem evoked response; (b) the extraction of single-trial ERPs from
      background EEG noise; (c) the decomposition of averaged ERP waveforms into
      orthogonal detail functions that isolate the waveform's experimental behavior in
      distinct, orthogonal frequency bands; and (d) the use of wavelet transform
      coefficients to concisely extract important information from ERPs that predicts
      human signal detection performance. In this tutorial we present an intuitive
      introduction to wavelets and the wavelet transform, concentrating on the
      multiresolution approach to wavelet analysis of ERP data. We then illustrate this
      approach with real data. Finally, we offer some speculations on future
      applications of wavelet analysis to ERP data.

PMID- 7626283
TI  - Effect of dexamethasone on antigen-induced high molecular weight glycoconjugate
      secretion in allergic guinea pigs.
AB  - The ovalbumin-sensitized guinea pig is commonly used as a small animal model of
      allergic asthma. This animal model exhibits many of the hallmark characteristics
      observed in patients afflicted with asthma including nonspecific airway
      hyperreactivity, airway eosinophilia, early and late phase bronchoconstriction,
      and plasma extravasation into the airways. In addition, mucous hypersecretion in
      the airways of asthmatic patients is thought to be responsible for the plugging
      of distal airways and to contribute to the morbidity and mortality associated
      with the disease process. In this study we examined whether the allergic guinea
      pig model exhibits an increase in airway high molecular weight glycoconjugate
      (HMWG) secretion in response to an antigen challenge and whether dexamethasone
      exerts any modulatory effects upon the response. Ovalbumin (OVA) -sensitized
      guinea pigs were challenged with OVA 2 wk following the initial exposure.
      Trachobronchoalveolar lavages (TBAL) were performed, and the samples were assayed
      for total eosinophil cell number, eosinophil peroxidase activity (EPO), and both
      acidic and neutral HMWG content. Morphometric analysis of mucous-containing cells
      was also performed on tissue sections prepared from the trachea, mainstem
      bronchus, and three lobes of the left lung. Within 24 h of an antigen challenge,
      TBAL samples obtained from the allergic guinea pigs exhibited increases in
      eosinophil cell number, measured EPO enzyme activity, and acidic HMWG content
      compared to TBAL samples prepared from vehicle-exposed animals. These antigen
      induced changes were dependent on the concentration of aerosolized OVA
      administered. Exposing the animals to 0.3% OVA provoked a 6.23-fold increase in
      airway eosinophils, 15-fold elevation in TBAL EPO enzyme activity, and 175%
      increase in TBAL acidic HMWG. No significant changes in TBAL neutral HMWG were
      measured. The changes in measured EPO activity correlated with the levels of
      acidic HMWG found in the TBAL samples (r = 0.73, P < or = 0.001). The measured
      increase in TBAL acidic HMWG was time dependent and was found to be maximal at 2
      h post-antigen challenge. Morphometric analysis of Alcian blue (pH 2.5) -stained
      airway sections showed a decline in stored mucosubstances following the antigen
      exposure, supporting the notion that the allergic guinea pig model exhibits a
      mucosecretory component. Pretreating the animals with dexamethasone attenuated
      the antigen-induced release of HMWG and changes in measured EPO activity. In
      conclusion, these data indicate that the allergic guinea pig may be a useful
      model for examining the neural and cellular mechanisms underlying mucus
      hypersecretion in individuals afflicted with bronchial asthma.

PMID- 7626284
TI  - Clara cell heterogeneity in differentiation: correlation with proliferation,
      ultrastructural composition, and cell position in the rat bronchiole.
AB  - Postnatal differentiation of nonciliated bronchiolar epithelial (Clara) cells
      occurs in a wave-like pattern beginning in the upper airways and ending in the
      terminal bronchiole. The heterogeneity of Clara cell differentiation observed
      during postnatal development in rats may be due to both cell turnover rate and
      cell position in the airways. To test the importance of these two factors in
      Clara cell differentiation, terminal bronchioles were examined in rats from
      gestational day 21 through postnatal day 100. The volume fraction of smooth
      endoplasmic reticulum (SER), a marker of differentiation, was seen to increase
      with age, while the epithelial cell labeling index of terminal bronchioles
      decreased over the same period. This represented a significant inverse
      correlation between SER volume density and cell proliferation rates (r2 = 0.80, P
      < 0.02). To evaluate the importance of cell position as a factor in cellular
      differentiation, the abundance of SER and secretory granules and the expression
      of cytochrome P450 isozyme 2B in Clara cells were examined along the entire
      length of the terminal bronchiole in animals 1, 21, and 100 days of age. For all
      three characteristics, Clara cells showed a similar degree of maturation from the
      proximal bronchiolar bifurcation to the bronchiole-alveolar duct junction (BADJ)
      (a span of approximately 35 cells). We conclude that during prenatal and
      postnatal bronchiolar development in rats: (1) the Clara cell is the most
      actively dividing cell type for the lower airways; (2) the stage of Clara cell
      differentiation is inversely related to Clara cell mitotic activity; and (3) the
      heterogeneity of Clara cell maturation and mitotic activity is not influenced by
      position within the terminal bronchiole.

PMID- 7626285
TI  - The evolutionary significance of pulmonary surfactant in lungfish (Dipnoi).
AB  - In this study, we characterized surfactant lipids from the lungs of the lungfish,
      Protopterus annectens, Lepidosiren paradoxa, and Neoceratodus fosteri
      (Sarcopterygiia: Dipnoi). We quantified the types of phospholipids present, the
      amounts of total phospholipid, disaturated phospholipid (DSP)--purported to be
      the primary surface tension-controlling agent--and cholesterol (CHOL), an
      important fluidizer. The surfactant phospholipid profiles of all three lungfish
      were very similar to each other and those of many other animals reported
      previously. Phosphatidylcholine was the dominant phospholipid (60% to 80%);
      phosphatidylglycerol was virtually absent; and there was a significant proportion
      of the combination of phosphatidylserine and phosphatidylinositol (10%). The
      Australian lungfish N. forsteri possessed a surfactant 5 times richer in CHOL and
      2 and 3 times poorer in DSP than the surfactant of the African lungfish P.
      annectens and the South American lungfish L. paradoxa, respectively. Hence, the
      CHOL/DSP mass ratio of N. forsteri was 12 and 20 times greater than that of P.
      annectens and L. paradoxa, respectively. Therefore, the surfactant composition of
      the two derived species of lungfish (P. annectens and L. paradoxa) very closely
      resembles that of amphibians, whereas surfactant from the primitive lungfish (N.
      forsteri) is almost identical to that of the primitive air-breathing
      actinopterygiian fish. Thus, it is likely that pulmonary surfactant had only a
      single origin, coinciding with that of the vertebrates. As with most nonmammalian
      vertebrates, it is possible that lungfish surfactant functions as an antiglue at
      low lung volumes or when the lungs are completely collapsed. Furthermore, it
      appears that within a species, an increase in lung development correlates with an
      increase in the relative amount of surfactant cholesterol and a decrease in the
      phospholipid saturation level.

PMID- 7626286
TI  - The role of tumor necrosis factor in increased airspace epithelial permeability
      in acute lung inflammation.
AB  - Increased airspace epithelial permeability is an early event in lung inflammation
      and injury. In this study, we have developed a rat model to study the mechanisms
      of the epithelial permeability to 125iodine-labeled bovine serum albumin (125I
      BSA), instilled intratracheally during acute lung inflammation. Epithelial
      permeability was measured as the percentage of instilled 125I-BSA appearing in
      the blood. The increase in epithelial permeability induced by intratracheal
      instillation of heat-killed Corynebacterium parvum produced a peak influx of
      neutrophils into the bronchoalveolar space at 16 h, which occurred after the peak
      increase in epithelial permeability (8 h). The increased epithelial permeability
      induced by C. parvum did not appear to be protease- or oxidant-mediated.
      Depletion of peripheral blood neutrophils was achieved by an intravenous
      injection of anti-neutrophil polyclonal antibody. The consequent profound
      reduction in neutrophil and macrophage influx into the airspaces 8 h after
      instillation of C. parvum reduced the epithelial permeability to control values.
      Bronchoalveolar lavage (BAL) leukocytes from rats 8 h, but not 16 h, after
      treatment with C. parvum caused a modest increase in epithelial permeability when
      re-instilled intratracheally into control rat lungs. Separation of the leukocytes
      before re-instillation indicated that macrophages rather than neutrophils were
      predominantly responsible for the increased epithelial permeability. The presence
      of dramatically increased levels of tumor necrosis factor (TNF) in BAL 8 h in
      contrast to a slight increase in BAL 16 h after C. parvum, the release of TNF
      from 8 h macrophages, the increased epithelial permeability induced by TNF in
      epithelial monolayers in vitro, and the inhibition of C. parvum-induced
      epithelial permeability by TNF antibody support the premise that TNF is a major
      player in the increased epithelial permeability that occurs during C. parvum
      induced acute alveolitis.

PMID- 7626287
TI  - Plasma membrane-bound and lysosomal peptidases in human alveolar macrophages.
AB  - Alveolar macrophages protect the lungs against noxious agents. Proteases and
      peptidases are essential for this defense and many metabolic activities. Human
      alveolar macrophages were evaluated for the presence of six important peptidases.
      Deamidase, a serine peptidase identical with the lysosomal protective protein and
      possibly with cathepsin A, had high specific activity in alveolar macrophages and
      is also present in cultured mouse J774A.1 and human U937 cells, used for the sake
      of comparison. In fractionated J774A cells, most of the deamidase activity was in
      the lysosomal fraction and in the final supernatant. Deamidase in human alveolar
      macrophages, obtained by bronchoalveolar lavage from 23 patients, cleaved dansyl
      Phe-Leu-Arg at a rate of 2.26 mumol/h/mg protein and hydrolyzed the chemotactic
      peptide N-f-Met-Leu-Phe even faster, at a rate of 53.1 mumol/h/mg protein, the
      highest activity for this enzyme with any of the cells we tested. Rabbit
      antiserum, elicited with the recombinant partial sequence of the enzyme,
      immunoprecipitated 77-88% of the macrophage deamidase. In immunocytochemistry,
      this antiserum localized deamidase within the human macrophages. The enzyme was
      inhibited by diisopropylfluorophosphate (DFP; 1 mM) and by ebelactone B (10
      microM), noncompetitively. The mRNA of deamidase was detected in mouse
      macrophages by Northern blot; the two protein chains of deamidase were shown in
      human macrophages by Western blot. In addition, two other serine peptidases were
      also highly active in macrophages: dipeptidyl peptidase IV (1.38 mumol/h/mg
      protein) and prolylcarboxypeptidase (0.72 mumol/h/mg protein). The activity of
      plasma membrane zinc metallopeptidases, neutral endopeptidase 24.11 and
      carboxypeptidase M, in contrast, was low or absent (angiotensin I converting
      enzyme; kininase II).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7626288
TI  - alpha-Thrombin increases cytosolic calcium and induces human airway smooth muscle
      cell proliferation.
AB  - In a variety of diseases including asthma, inflammation causes microvascular
      leakage and activates thrombin. In addition to cleaving fibrinogen to fibrin,
      thrombin may have other important cellular effects. Because airway inflammation
      and vascular permeability are important determinants of airway hyperreactivity,
      we have studied the effects of thrombin on airway smooth muscle. Using cultured
      human airway smooth muscle cells, we have examined whether alpha-thrombin can
      evoke calcium responses, phosphoinositide turnover, or cell proliferation. We
      have demonstrated that alpha-thrombin does increase cytosolic calcium and
      phosphoinositide hydrolysis in a dose- and time-dependent manner that may be
      inhibited by pretreating cells with r-hirudin. In addition, we have shown that
      thrombin stimulates airway smooth muscle cell proliferation. By contrast,
      bradykinin, which evoked comparable increases in cytosolic calcium and
      phosphoinositide turnover, did not stimulate airway smooth muscle cell growth. We
      conclude that thrombin effectively increases cytosolic calcium and induces PI
      hydrolysis and, in addition, is capable of stimulating airway smooth muscle cell
      growth. However, the lack of an effect of bradykinin on cell growth suggests that
      increases in calcium and PI turnover alone will not induce airway smooth muscle
      cell proliferation. We suggest that alpha-thrombin may be important in the
      pathogenesis of both increased airway resistance as well as the structural
      changes seen as a consequence of chronic asthma.

PMID- 7626289
TI  - Muscarinic regulation of cyclic AMP in bovine trachealis cells.
AB  - The goal of this study was to characterize the receptors and coupling mechanisms
      mediating muscarinic inhibition of adenylyl cyclase activity in bovine tracheal
      smooth muscle. In radioligand binding experiments, methoctramine and AF-DX 116
      competed for approximately 85% of the 3H-quinuclidynyl benzilate (3H-QNB) binding
      sites on intact cells with high affinities (-log KI of 7.73 +/- 0.16 and 6.67 +/-
      0.31, respectively) characteristic of binding to M2 receptors. The antagonist 4
      diphenylacetoxy-N-methylpiperidine (4-DAMP) bound the receptors on intact cells
      with an affinity (-log KI = 7.76 +/- 0.21) characteristic of binding at M2
      receptors. In experiments measuring 3',5'-cyclic adenosine monophosphate (cAMP)
      accumulation, methoctramine, AF-DX 116, and 4-DAMP antagonized the inhibitory
      effect of carbachol on isoproterenol-stimulated cAMP accumulation with potencies
      consistent with mediation by M2 muscarinic receptors (-log Kb of 8.01 +/- 0.22 to
      7.58 +/- 0.25 for methoctramine; 7.43 +/- 0.36 to 7.02 +/- 0.30 for AF-DX 116;
      and 7.60 +/- 0.21 for 4-DAMP). In other experiments, 24 +/- 3% of the inhibitory
      effect of carbachol was not reversed by 60 min exposure to atropine. Moreover,
      pertussis toxin (10, 250, and 1,000 ng/ml) decreased only a portion of the
      inhibitory effect of carbachol (8 +/- 19%, 32 +/- 10%, and 33 +/- 8%,
      respectively) on cAMP accumulation. These findings indicated that M2 receptors
      were coupled to adenylyl cyclase in trachealis cells, but that coupling
      mechanisms in addition to those of pertussis toxin-sensitive guanine nucleotide
      binding proteins were involved. Since the inhibitory effect of carbachol (10(-8)
      M) on isoproterenol-stimulated cAMP accumulation was decreased from 20 +/- 4% to 
      1 +/- 5% (n = 6) by okadaic acid (1 microM), protein phosphatases may regulate
      the processes coupling muscarinic receptors to adenylyl cyclase.

PMID- 7626290
TI  - Tryptase, the dominant secretory granular protein in human mast cells, is a
      potent mitogen for cultured dog tracheal smooth muscle cells.
AB  - Hyperplasia of airway smooth muscle cells is present in the airways of asthmatic
      patients and may contribute to the development of the bronchial
      hyperresponsiveness that occurs in these patients. Because tryptase is an
      abundant component of mast cell granules and has demonstrated growth-stimulatory
      effects in other mesenchymal cells (J. Clin. Invest. 1991; 88:493-499), the goal
      of our study was to determine whether tryptase is a mitogen for airway smooth
      muscle cells. The mitogenic effects of tryptase were tested in passages 1 through
      5 of dog tracheal smooth muscle cells, either by counting smooth muscle cells or
      by monitoring uptake of bromodeoxyuridine (BrdU) into cellular DNA during S
      phase. With respect to its efficacy, at a near maximal concentration (4 nM),
      tryptase increased cell numbers 2.1 +/- 0.2- or 2.8 +/- 0.6-fold above controls
      after 2 or 4 days, respectively, and these increases were approximately the same
      as those induced by platelet-derived growth factor (50 ng/ml) or 10% calf serum.
      With respect to potency, tryptase caused concentration-dependent increases in
      BrdU uptake, as detected in an enzyme-linked immunosorbent assay or by counting
      BrdU-labeled nuclei, with an EC50 of 2 nM. Pretreatment of tryptase with
      diisopropylfluorophosphate, to reduce markedly its catalytic as a activity as a
      proteinase, attenuated its growth-stimulated effects by 58 +/- 16%. Tryptase
      induced mitogenesis was not a nonspecific effect of all serine proteinases,
      because thrombin, another proteinase with mitogenicity for fibroblasts,
      stimulated neither increases in cell counts nor BrdU uptake in our cells. We
      conclude that tryptase is a potent mitogen for airway smooth muscle cells in
      culture.

PMID- 7626291
TI  - Oxidant tone regulates IL-8 production in epithelium infected with respiratory
      syncytial virus.
AB  - Respiratory syncytial virus (RSV) is an important respiratory pathogen that
      preferentially infects epithelial cells in the airway, and causes a local
      inflammatory response. Although it has been previously demonstrated that RSV
      infected airway epithelial produce cytokines, including interleukin-8 (IL-8),
      which contributes to the inflammatory response, the regulation of this effect of
      RSV is unknown. To further characterize the mechanisms by which RSV infection
      triggers release of IL-8, we first exposed cultured A549 cells to RSV, and
      measured IL-8 release via enzyme-linked immunosorbent assays (ELISA), and IL-8
      messenger RNA (mRNA) induction via Northern blot analysis. We observed a dose-
      and time-dependent release of IL-8 in response to RSV. The optimal dose of RSV
      was 10(4) TCID50/ml, and maximal release of IL-8 was measured at 72 to 96 h after
      infection. RSV induced a biphasic (early and late) increase in IL-8 mRNA. The
      early phase was independent of viral infection, whereas the more pronounced late
      phase required the presence of live virus and infection of the epithelium.
      Partial (< 50%) cytopathic effects were noted at 48 h and progressed to 75% at 96
      h. The monolayer was still intact at 96 h. Inhibitors of nitric oxide, including
      NG-monomethyl-L-arginine (L-NMMA), NG-nitro-L-arginine methyl ester (L-NAME), and
      aminoguanidine had no effect on IL-8 release or IL-8 mRNA induction. We did,
      however, demonstrate a dose-dependent decrease in IL-8 release and IL-8 mRNA
      induction in RSV-infected epithelial treated with the antioxidants dimethyl
      sulfoxide (DMSO) or 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). Peak effects were
      noted at a concentration of 2% DMSO and 50 microM DMPO. The antioxidants did not
      inhibit viral replication or infection. This data suggest that RSV-induced IL-8
      production in airway epithelium is mediated via changes in oxidant tone. The data
      also suggest a potential therapeutic role for antioxidants in RSV infections.

PMID- 7626293
TI  - [Barrett esophagus. An epidemiological study in an area of Spain].
AB  - Barrett's esophagus is defined as the replacement of squamous normal mucosa by
      columnar specialized epithelium, being its main importance its preneoplastic
      potential. In this retrospective study on 5303 gastrointestinal endoscopies, done
      in 8 years, we describe, for the first time the gross prevalence and incidence
      rates in a Spanish country. We found 28 cases of Barrett's esophagus, what means
      a prevalence rate of 0.53% of all endoscopies, and an incidence rate of
      26.4/100,000 inhabitants of our hospital referred population, with an estimated
      incidence rate of 3.3 cases/100,000 inhabitants/year. The prevalence rate of
      Barrett's esophagus adenocarcinoma--3 cases--was 10.71%, and the incidence rate
      of 1 case/104 Barrett's esophagus/year, follow-up similar to that of other
      authors.

PMID- 7626292
TI  - A point mutation in the integrin beta 6 subunit abolishes both alpha v beta 6
      binding to fibronectin and receptor localization to focal contacts.
AB  - The integrin alpha v beta 6 was initially identified from primary cultures of
      airway epithelial cells. This integrin is expressed in bronchiolar and alveolar
      epithelium during development and in settings of injury and/or inflammation and
      mediates attachment of epithelial cells to fibronectin and tenascin. Like other
      integrins, this receptor localizes to structures called focal contacts in cells
      plated on appropriate ligands. In the present study, we produced a mutant beta 6
      cDNA (beta 6m) containing a single substitution of Asp140 with Ala and
      transfected mutant (or wild-type) beta 6 cDNA into the human colon carcinoma cell
      line SW480. In parallel, we used cDNAs truncated just proximal to the
      transmembrane domain to generate secreted forms of mutant alpha v beta 6 in
      Chinese hamster ovary (CHO) cells. The mutant beta 6, like the wild type, formed
      heterodimers with human alpha v that were expressed on the cell surface of SW480
      cells and secreted by CHO cells. Secreted alpha v beta 6 containing this point
      mutation did not bind to fibronectin-Sepharose. Furthermore, in contrast to wild
      type beta 6, the mutant form did not allow SW480 cells to bind to fibronectin in
      the presence of beta 1-blocking antibody and did not localize to focal contacts.
      Our results confirm that the Asp140 of beta 6, like the corresponding residues in
      beta 1 (Asp130) and beta 3 (Asp119), is critical for interactions of alpha v beta
      6 with ligand, and also suggest that ligand binding to alpha v beta 6 is
      necessary for localization of this receptor to focal contacts.

PMID- 7626294
TI  - [A comparative study of 2 technics of percutaneous endoscopic gastrostomy].
AB  - OBJECTIVE: To compare the two most frequently used methods of percutaneous
      endoscopic gastrostomy: Pull-string Ponsky-Gauderer type and Push-over-wire Sachs
      Vine gastrostomy. PATIENTS AND METHODS: Forty-four patients with oral feeding
      incapacity were prospectively randomized to one of the two methods of
      percutaneous endoscopic gastrostomy. In 22 patients the Ponsky-Gauderer type were
      used and in the other 22 the Sachs-Vine gastrostomy were employed. In every case
      the gastrostomy tube was replaced 4-5 months after its placement by a Flexiflo
      tube. The mean follow-up of the patients was 7.3 months (range: 4-18). RESULTS:
      Gastrostomy was successful in every case. No differences were found between the
      two procedures in technical difficulties or complications during gastrostomy
      placement. Wound infection occurred in 6 patients (13%), 3 in each group, and in
      all cases it was cured with topic antibiotic treatment administered through the
      gastrostomy. Tube dislodgement was observed in 3 patients in the Ponsky-Gauderer
      group (soft internal with-holder). The only significant difference between the
      two procedures was found at the removal of the gastrostomy tube. In the Sachs
      Vine type the removal of the tube was always endoscopically performed (due to the
      presence of a rigid internal with-holder), while the Ponsky-Gauderer type was
      always done by traction (soft internal with-holder). No related procedure
      mortality was found with any of the two techniques. CONCLUSION: Both percutaneous
      endoscopic gastrotomy techniques are similar in efficacy, safety and morbidity
      and they prove to be a valid alternative to surgical gastrostomy in patients with
      oral feeding incapacity.

PMID- 7626295
TI  - [Inflammatoru bowel disease in Aragon: a more and more frequent diagnosis].
AB  - OBJECT: To study the frequency of inflammatory bowel disease in our area.
      MATERIAL AND METHODS: A retrospective, hospital-based analysis identifying
      potential cases, with a posterior study of case records following a predefined
      protocol, according to international standards in diagnosis. PATIENTS: All
      patients with a confirmed diagnosis of Crohn's disease, ulcerative colitis, or
      indeterminate colitis established between 1975 and 1992 at our Hospital. RESULTS:
      222 cases (ulcerative colitis: 109; Crohn's disease 93; indeterminate colitis 20)
      were identified and a clear trend for an increased incidence was found for the
      three diagnoses; with annual incidence below 1 for them all in the 1975-1977
      period versus 3.66; 3.33; and 1 respectively in the 1990-1992 period. This trend
      was evident both for ulcerative colitis and Crohn's disease. CONCLUSIONS: The
      global frequency of inflammatory bowel disease has increased in the last years in
      Zaragoza (Spain), and its incidence in now very similar to that reported in
      northern European countries. Possible factors associated with this phenomenon
      should be pursued in future studies.

PMID- 7626296
TI  - [Colorectal cancer in the context of multiple primary malignant neoplasms].
AB  - INTRODUCTION: The finding of more than one carcinoma throughout the life of a
      patient is not unusual. In fact, the occurrence of multiple primary cancers has
      been well documented. However, the features, implications and prognosis of
      colorectal cancers associated to other malignancies, have been less well
      documented. PATIENTS AND METHOD: We report 29 patients with multiple primary
      neoplasms in which at least one of them was a colorectal cancer. Number,
      extension and localization of colonic neoplasm, and time interval between
      diagnosis of both neoplasms, and mortality and survival rate were retrospectively
      analyzed. Follow-up ranged from 1 to 360 months. RESULTS: Twenty three patients
      had two cancers, and six more than three neoplasms. Colorectal cancer was primary
      in 8 patients, metachronous in 14 patients and synchronous in 5 patients. Breast
      (7 cases), prostate (5 cases), endometrium (3 patients) and stomach (3 cases),
      were the other malignancies most frequently detected. Overall, 13 of the 27
      patients (49%) died during the follow-up period after the recognition of the
      colorectal cancer. Two patients were lost to follow-up. Mantel-Haenszel test did
      not show significative differences in survival between patients with two or more
      neoplasms. There were no differences in survival depending upon the timing of
      diagnosis of the colorectal tumor. CONCLUSIONS: These data suggest that
      colorectal cancer may share etiologic factors with hormone-dependent neoplasms
      (breast, prostate) and gastric cancer. In patients with primary multiple
      neoplasms, the number of neoplasms detected and the interval time between both
      diagnosis are not prognostic factors when one of the malignancies in colorectal
      cancer.

PMID- 7626297
TI  - [Imaging technics in the study of focal liver lesions].

PMID- 7626298
TI  - [The diagnosis of aorticomesenteric duodenal compression by magnetic resonance
      angiography].
AB  - The syndrome of duodenal obstruction by the mesenteric artery is an infrequent
      condition that nevertheless was too often diagnosed in the past. The development
      of modern imaging techniques has presently restricted the diagnosis of this
      syndrome. We report the case of a 21-year-old patient with superior mesenteric
      artery-induced duodenal compression syndrome secondary to malnutrition and loss
      of weight. Diagnosis was confirmed by the evaluation of bowel transit, CT Scan,
      NMR and angio-MR. Conservative treatment with total parenteral nutrition proved
      ineffective. Surgical sectioning of the ligament of Treitz and extensive
      mobilization of the duodenum (Strong's operation) was performed; outcome was
      unsatisfactory, however. A duodenojejunostomy was performed later, which finally
      solved the condition. We emphasize the diagnostic usefulness of CT Scan and angio
      MR, and the favorable results afforded by duodenojejunostomy.

PMID- 7626300
TI  - [Hepatic fascioliasis: the usefulness of CT and US].
AB  - We present a case report of invasive hepatic fascioliasis. Ramified hypodense
      lesions with peripheral distribution were found in the CT-scan. These lesions
      disappeared after treatment with Bithionol. CT-scan plays an important role in
      the diagnosis of invasive fascioliasis whereas ultrasound is useful in the
      chronic phase. Both are helpful to evaluate response to treatment.

PMID- 7626299
TI  - [Diarrhea, rectorrhagia and colonic ulceration following the ingestion of
      NSAIDs].
AB  - The lower digestive tract, in contrast to the gastroduodenal tract, is
      infrequently affected by non-steroidal antiinflammatory drugs (NSAID), and rarely
      referred to in medical literature. We report the case of a 40-year-old man who
      presented with bloody diarrhea following treatment with NSAID. The fiber
      gastroscopy was normal. The fiber colonoscopy showed elongated aphthous ulcers
      with fibrin in the sigmoid colon. Others studies were normal. After withdrawal of
      NSAID, the patient returned to normal, as did the fiber colonoscopy. The
      treatment with NSAID has been linked with ulcerative lesions in the lower
      digestive tract, perforation, bloody lesions, perforation of diverticuli,
      reactivation of quiescent colitis and stenosis. In spite of this, doubts persist
      about the frequency of presentation, high risk doses and its pathophysiological
      mechanism, which probably involves blocking the cyclooxigenase system and the
      formation of the leukotrienes and free oxygen radicals. Taking into consideration
      the above factors, more care should be taken in investigating colonic involvement
      in patients who present with gastrointestinal bleeding following treatment with
      NSAID.

PMID- 7626301
TI  - [Cirrhosis caused by amiodarone].
AB  - A woman who had been taking amiodarone--400 mg/day--for over nine years,
      developed cirrhosis. Electron microscopy showed phospholipid-laden lysosomal
      lamellar bodies containing myelin figures. A review is made about the reported
      cases of amiodarone-induced cirrhosis, including detailed histological findings.
      We conclude that periodical clinical and biochemical monitoring must be made in
      patients receiving treatment with amiodarone, and that the pathophysiologic
      mechanism responsible for the amiodarone toxicity still remains unclear.

PMID- 7626302
TI  - [The role of laparoscopy in the diagnosis of primary peritoneal mesothelioma].
AB  - In this study we demonstrate the usefulness of laparoscopy on the diagnosis of
      some unusual causes of ascites, such as primary mesothelioma, usually overlooked
      by other diagnostic modalities, like ultrasound, computed tomography and cytology
      of the ascitic fluid. We describe three cases of primary peritoneal mesothelioma
      among 27 patients with exudative ascites submitted to laparoscopy at our
      institution during the past two years. The final diagnosis inaccessible to the
      conventional diagnostic modalities, was reached only by laparoscopy.

PMID- 7626303
TI  - [Spontaneous bacterial peritonitis due to Listeria monocytogenes].
AB  - We present a case of spontaneous bacterial peritonitis (SBP) caused by Listeria
      monocytogenes in a patient previously diagnosed as alcoholic liver cirrhosis. The
      clinical presentation, biochemical data and outcome of the patient are compared
      with those of cases of SBP caused by Listeria monocytogenes in patients with
      cirrhosis published in the Spanish and English literature. Twelve out of 20 cases
      described in the literature were published by Spanish authors. This greater
      proportion could be related to dietary habits (greater consumption of fruits and
      vegetables), climatic or demographic factors. We underline the importance of
      pursuing a microbiological diagnosis since Listeria monocytogenes is
      intrinsically resistant to cefotaxime, the antimicrobial often selected to
      empirically treat SBP episodes.

PMID- 7626304
TI  - [THe treatment of anal fissures by lateral internal sphincterotomy].

PMID- 7626305
TI  - [Ticlopidine-induced cholestatic hepatitis].

PMID- 7626306
TI  - [Hepatic hemangiomas: an atypical echographic presentation].

PMID- 7626307
TI  - 1995 legislative platform. American Academy of Nurse Practitioners.

PMID- 7626308
TI  - Functional health status of older women.
AB  - By the year 2000 in the United States, there will be 32 million adults age 65 or
      over, representing 12% of the population, with the majority being women. Older
      women are experiencing greater longevity but worse overall health than men. The
      assessment of functional health status in older women is often neglected yet is
      the major contributor to independent living. Functional health status includes
      the dimensions of physical health, independent health, and psychosocial health.
      Studies of two different groups of non-institutionalized older women who reside
      in the same Southwestern state are discussed in relation to national study
      samples and implications for nurse practitioners.

PMID- 7626309
TI  - Transient ischemic attacks (TIA): current issues in diagnosis and management.
AB  - Transient ischemic attacks (TIAs) affect more than 500,000 Americans each year.
      Stroke risk approximates 4% to 8% within 1 month and increases to 12% to 13% at
      one year. This has led to stroke being one of the leading causes of death and
      disability. TIAs are focal neurologic events that are temporary in nature and
      warn of potential stroke. Most TIAs resolve within 24 hours. Hypertension,
      smoking, heart disease, and diabetes are the major risk factors for stroke. A
      comprehensive history of symptoms can help identify carotid vs. vertebrobasilar
      disease. Timely evaluation of TIAs should be performed according to recent
      guidelines set forth by the American Heart Association. Aspirin continues to be
      the gold standard for stroke prevention, conferring a 48% risk reduction in
      stroke or death. The use of ticlopidine has been recommended as a second-line
      agent in patients with aspirin intolerance. Surgical intervention (carotid
      endarterectomy) is indicated in symptomatic patients with high grade stenosis of
      70% or greater. For patients with less significant stenosis, inconclusive data
      exists regarding the benefit of medical vs. surgical treatment. Patient education
      should address identification of symptoms, the need for prompt medical attention,
      and risk factor modification. A collaborative plan between clinician and client
      will facilitate early intervention ultimately leading to preservation of function
      and prevention of the catastrophic sequelae of stroke.

PMID- 7626310
TI  - Domestic violence.

PMID- 7626311
TI  - Successful treatment of hyperphosphatemic tumoral calcinosis with long-term
      acetazolamide.
AB  - We describe a patient with tumoral calcinosis, in which acetazolamide (ACZ) was,
      for the first time, tested for its therapeutic efficacy. The 19-year-old Japanese
      man had been suffering from multiple recurrent calcific masses with tenderness
      around the finger, knee, and toe joints since 10 months of age. Radiographs
      revealed several calcific subcutaneous masses around the finger joints, and
      calcific myelitis around the right knee joint and in the calvarium. The patient
      had hyperphosphatemia with elevated maximal threshold of renal phosphate
      excretion in the presence of normal kidney function and normocalcemia, suggesting
      a reduced ability to excrete phosphorus in the urine. A delay of disappearance of
      orally administered phosphate from the blood stream was found. A serum
      parathyroid hormone (PTH) level was normal, and responses to PTH and ACZ were
      also normal regarding the induction of phosphaturia. Since the masses tended to
      recur easily despite repeated surgical resections, we started medical treatment
      with phosphorus deprivation by oral aluminum hydroxide. However, the drug alone
      had no effect on hyperphosphatemia or calcific lesions, and ACZ was added in
      expectation of making the patient's phosphorus balance negative by its
      phosphaturic effect. Fourteen years of administration of the two drugs apparently
      improved the patient's symptoms, the biochemical findings, and the calcific
      lesions on radiographs. Thus, ACZ appeared to be useful for tumoral calcinosis
      resistant to phosphorus deprivation by aluminum hydroxide alone.

PMID- 7626312
TI  - Patellar ultrasound transmission velocity in healthy children and adolescents.
AB  - Apparent velocity of ultrasound (AVU) (Signet, Osteo-Technology Cambridge, MA) at
      the patella was measured on 568 children and adolescents, aged 8 to 18 years.
      Trend analysis revealed a significant trend (p < 0.004) toward increasing AVU
      with increasing age and increasing Tanner stage. Height and weight were
      positively correlated with AVU in both sexes, while dietary intake of calories,
      protein, and calcium were positively correlated with AVU in males, but not in
      females. Multiple linear regression revealed that 29% of the variance of AVU in
      females was described by Tanner stage (p < 0.002) and height (p < 0.007). The
      best regression model for males accounted for 48% of the variance in AVU and
      included age (p < 0.0001) and protein intake (p < 0.01). Bone quality has a
      distribution in children which is similar to the distribution of bone mass and
      density. Our patellar AVU values can be used as a baseline for much-needed
      prospective research with children and adolescents.

PMID- 7626313
TI  - Vertebral dimension measurements improve prediction of vertebral fracture
      incidence.
AB  - We investigated the independent contributions of vertebral size and shape, bone
      density, and existing fractures for predicting the risk of new vertebral
      fractures among postmenopausal Japanese-American women in Hawaii. Baseline
      measurements of bone density at the distal and proximal radius and the calcaneus
      were obtained in 1981, and at the lumbar spine in 1984. Incident fractures were
      documented on serial radiographs during an average of 8.0 years of follow up of
      840 women. A positive difference of 1 standard deviation in vertebral depth
      increased the risk of new vertebral fractures by approximately 1.3-fold (95%
      confidence interval = 1.03, 1.66) after controlling for bone density and
      prevalent fractures. A combination of large vertebral depth (above the 66th
      percentile) and low bone density (below the 33rd percentile) increased fracture
      risk approximately six times compared to women with high bone density (above the
      66th percentile) and small vertebral depth (below the 33rd percentile). We
      conclude that combining information about vertebral depth, bone density, and
      prevalent fracture appears to be better for predicting new fractures than any
      single variable alone.

PMID- 7626314
TI  - Different effects of cyclosporin A on bone remodeling in young and adult rats.
AB  - Reported effects of cyclosporin A (Sandimmun, CsA) on bone have been both
      contradictory and controversial. Thus, stimulation of new bone formation as well
      as increased mineral and matrix resorption have been observed. To investigate the
      response of basal mineral and matrix turnover to CsA treatment at different
      stages of skeletal development, comparative experiments were conducted in young
      growing female rats and in adults. Fifty-six young animals (study A) and 40
      adults (study B) received orally either the carrier substance or 5, 15, and 30
      mg/kg CsA for 30 days. The following parameters were measured: (a) total skeletal
      mineral content by dual energy X-ray absorptiometry (DEXA) on days 1 and 30; (b)
      tibial trabecular volume at day 30; (c) serum osteocalcin at 5-day intervals; (d)
      urinary deoxypyridinoline (Dpd) excretion (days 1, 15, and 30); and (e) plasma
      levels of CsA. Results can be summarized as follows: in young rats (study A),
      total skeletal mineral was not modified by the 5- and 15-mg/kg doses of CsA,
      whereas 30 mg/kg induced a significant decrease (-15%, p < 0.01). This parameter
      was not significantly modified in adult animals (study B) subjected to the same
      doses. The administration of 5 mg/kg CsA did not alter tibial trabecular volume
      in young rats, but 15 and 30 mg/kg significantly lowered this parameter (-16.3%,
      p < 0.02, and -42%, p < 0.001, respectively). In adult rats, tibial trabecular
      volume remained unchanged with the exception of the group receiving 30 mg/kg
      which exhibited significantly lower values (-28%, p < 0.001).(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7626315
TI  - The potential of sheep for the study of osteopenia: current status and comparison
      with other animal models.
AB  - There is a great need to develop an animal model for postmenopausal osteoporosis;
      a model that will be useful for the understanding of the pathogenesis of the
      disease as well as the investigation of new therapies. The requirements for such
      an animal model are discussed and ones that have been used in the past include
      nonhuman primates, dogs, cats, rodents, rabbits, guinea pigs, and minipigs.
      Advantages and disadvantages of these models are briefly reviewed. Sheep are a
      promising model for various reasons; they are docile, easy to handle and house,
      relatively inexpensive, available in large numbers, spontaneously ovulate, and
      have hormone profiles similar to women. Ovariectomy results in a slight loss of
      bone from the ovine iliac crest, and biochemical markers such as osteocalcin are
      well characterized. Physiological disadvantages are lack of natural menopause,
      that normal estrus cycles are restricted to fall and winter and that they have a
      different gastrointestinal system. Sheep have cortical bone that is plexiform in
      structure although haversian remodeling is seen in older animals. When and if
      biomechanical incompetence of bone follows ovariectomy is presently unknown.
      There is no ideal model for the study of postmenopausal osteoporosis; all have
      advantages and disadvantages. Researchers in this field must recognize the
      limitations of the model they choose, and select one that will fulfill their
      needs.

PMID- 7626316
TI  - Effects of large doses of olpadronate (dimethyl-pamidronate) on mineral density,
      cross-sectional architecture, and mechanical properties of rat femurs.
AB  - As part of a safety-assessment study, doses of 8, 40, and 200 mg/kg per day, 6
      days per week, of sodium olpadronate (dimethyl-APD, Me2-APD) were given by gavage
      to 10-week-old male and female rats during 27 weeks. Only the 200 mg/kg per day
      dose provoked toxic effects and a meaningful growth depression, regardless of the
      animal gender. In male animals, doses of 40 or 200 mg/kg per day improved
      strength, stiffness, and cross-sectional moment of inertia (CSMI) of femur
      diaphyses despite the toxic effects observed at the highest dose. Changes in bone
      mechanical properties were a consequence of those induced in CSMI. Regression
      analyses showed a treatment-induced improvement in bone modeling (as assessed by
      CSMI) for the same level of bone material stiffness (as expressed by calculated
      values of elastic modulus). The high dependency of results on body mass bearing
      suggested that these effects were exerted through an increase in the efficiency
      of bone mechanostat. Strikingly, they were not evident in female rats. If not
      related to a lower bone bioavailability of bisphosphonates in female rats as
      described by others, this phenomenon may have reflected: (1) their a smaller
      biomass; and/or (2) a less effective mechanostatic regulation of bone
      architecture derived from a higher bone material stiffness related to male
      animals. An increase of BMD with a predominance toward the distal region was
      observed in all femurs studied. This effect, unrelated to the observed changes in
      mechanical properties, seems to express a lack of remodeling of primary cartilage
      or bone tissue.

PMID- 7626317
TI  - Heterogeneous decrease of bone mineral density in the vertebral column of
      ovariectomized rats.
AB  - The long-term effect of ovariectomy on the loss of bone mineral density (BMD) was
      evaluated in rats with and without estrogen treatment; BMD was studied in the
      lumbar and caudal vertebrae, measured by DXA, to find how the losses of BMD occur
      in the axial skeleton. Seventy female Wistar rats of 3 months of age were divided
      into four groups as follows: group 1: control animals; group 2: ovariectomized
      animals; group 3: ovariectomized animals undergoing treatment with estrogen (0.25
      mg/kg per week of 17-beta estradiol); group 4: ovariectomized rats undergoing
      estrogen treatment only during the last 3 months of the experimental period. No
      significant differences were found among the groups in regard to the BMD values
      of the caudal vertebrae at either 3 or 6 months. Likewise, in the lumbar
      vertebrae there were no significant differences among the groups after 3 months.
      However, at 6 months, a decrease in the BMDs of the ovariectomized animals with
      respect to the remaining groups was found: 226 +/- 11 mg/cm2 in the
      ovariectomized group; 262 +/- 14 mg/cm2 in the controls; 255 +/- 4 mg/cm2 in the
      rats receiving estrogen treatment for 6 months; and 259 +/- 5 mg/cm2 in the
      animals receiving estrogen for 3 months. The study also reveals the absence of
      differences in the bone mineral density between the ovariectomized and control
      rats when the former received estrogen treatment.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7626318
TI  - Calcium absorption, endogenous excretion, and endocrine changes during and after
      long-term bed rest.
AB  - Negative calcium balance is a known consequence of bed rest, and is manifested in
      elevated urine and fecal calcium (Ca). Elevated fecal Ca can result from either
      decreased absorption, increased endogenous fecal excretion, or both. We measured
      the Ca absorption and endogenous fecal excretion in eight healthy male volunteers
      before and during 4 months of bed rest. Dual isotope (n = 6) or single isotope (n
      = 2) methods in conjunction with Ca balance were used to calculate true and net
      Ca absorption and endogenous fecal excretion. Stool Ca increased from 797 mg/day
      (mean intake 991 mg/day) to 911 mg/day during bed rest, whereas urine Ca
      excretion increased from 174 to 241 mg/day. True Ca absorption decreased from 31
      +/- 7% of Ca intake pre-bed rest to 24 +/- 2% during bed rest, (p < 0.05) and
      returned toward pre-bed rest values within 5-6 weeks following reambulation.
      Endogenous fecal excretion did not change significantly, and therefore, most of
      the increased fecal Ca resulted from changes in absorption. However, in one
      individual, endogenous fecal Ca excretion was the major contributor to Ca loss.
      Ionized Ca and pyridinium crosslinks increased and 1,25(OH)2 vitamin D decreased
      during bed rest, similar to the decrease in Ca absorption; parathyroid hormone
      (PTH), calcitonin, serum albumin, phosphorus, and total serum Ca were unchanged.
      Although alkaline phosphatase, osteocalcin, and PTH were unchanged during bed
      rest, they were elevated during reambulation. These changes accompanied by
      increased Ca absorption and balance and decreased ionized and total serum Ca
      suggest a rebound in bone formation following immobilization.

PMID- 7626319
TI  - Cell proliferation within the growth plate of the tich mouse.
AB  - The pattern of chondrocyte proliferation was studied in the proximal tibial
      growth plate of tich mice (gene symbol tch), a recessive mouse mutant, which is
      coisogenic with the A.TL strain. Specimens were qualitatively studied at time
      points of 2, 3, 4, 6, and 8 weeks of age by bromodeoxyuridine labeling of cell
      division and routine histology. At 2 weeks, when the lesion appeared as a full
      width thickening of the growth plate, a greater proportion of cells appeared
      positively labeled in the proliferative zone. This concavity in the central
      portion of the growth plate became progressively more focal between 3 and 4 weeks
      to give a "tongue" of unresorbed, noncalcified cartilage in the central region of
      the tich growth plate. BrdUrd labeling indicated that the appearance of the
      cartilage tongue corresponded with increased cell division in the central region
      of the growth plate. At the same time, a "second" zone of cell division formed,
      within the zone of hypertrophy, such that labeled cells appeared to be set among
      chondrocytes with hypertrophic morphology. At stages after 4 weeks of age the
      focal feature disappeared as the growth plate returned to more normal morphology
      by maturity. It seems that this unique "second" zone of dividing cells may
      contribute to formation of an elongation of the nonresorbed tongue of cartilage.
      However, it is not likely to be the primary defect since growth plate changes
      were apparent at earlier stages.

PMID- 7626321
TI  - Effects of bisphosphonates APD and HEBP on bone metabolism in vitro.
AB  - Although the effects of the bisphosphonates on resorption have been well
      documented, their effects on bone formation are not as clear. Therefore, this
      investigation was undertaken to elucidate the role played by bisphosphonates in
      the regulation of bone formation in vitro. To evaluate bisphosphonate-mediated
      regulation of bone formation in vitro, the effects of two drugs, ethane-1
      hydroxy,1-diphosphate (Etidronate) (HEBP), and the second-generation
      bisphosphonate, disodium-1-hydroxy-1-aminopropylidine-1,1-diphosphate
      (Pamidronate) (APD), were assessed in the chick periosteal osteogenesis (CPO)
      model. In this study, drug-induced changes in alkaline phosphatase were assessed
      at the cellular level by means of quantitative fluorescence histochemistry.
      Cellular proliferation was quantified by means of autoradiography
      ([3H]thymidine). Mineralization and matrix production were measured
      morphometrically, whereas collagen synthesis and degradation were measured
      biochemically. The data suggest that in addition to their effects on bone
      resorption, the bisphosphonates have marked and direct effects on bone formation
      and other parameters of osteogenesis. HEBP may affect cellular proliferation (75
      80% reduction, p < 0.05) in zones distant from bone; alkaline phosphatase
      positive cell numbers were increased in the osteoblastic layer of cells (twofold
      relative to control, p < 0.05) in 12-day cultures. HEBP, but not APD, prevented
      mineralization-induced suppression of matrix synthesis in early stages of
      culture. In 6-day cultures induced to mineralize with beta-glycerophosphate, (GP)
      cotreatment with HEBP induced a 70% increase in collagen synthesis. In addition,
      degradation of collagen in the CPO cultures was inhibited by HEBP (25%) and to a
      lesser extent by APD (8%). Although there were no differences in bone-osteoid
      areas measured in 12-day cultures treated with various regimens of bisphosphonate
      or GP, a clear increase in bone-osteoid area was detected in 6-day cultures
      treated with GP and HEBP as compared to GP only. This may suggest that initially,
      osteoblasts may be induced to synthesize increased volumes of bone matrix when
      mineralization is inhibited (e.g., with HEBP), but that over time the osteoblasts
      make the same amount of matrix. Taken together, these findings indicate that
      whereas the bisphosphonates do have well-documented effects on bone resorption,
      their effects on bone formation may also be important.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 7626322
TI  - Colony-stimulating factor 1 when combined with parathyroid hormone or 1,25
      dihydroxyvitamin D can produce osteoclasts in cultured neonatal metatarsals from
      toothless (tl-osteopetrotic) rats.
AB  - Toothless (tl-osteopetrotic) rats have little or no endogenous bone resorption,
      no marrow spaces, and very few osteoclasts and macrophages, and their live
      metatarsal rudiments cannot support the development of normal osteoclasts in
      vitro. The recent demonstration that exogenous colony-stimulating factor 1 (CSF
      1) improves skeletal sclerosis and increases osteoclasts in tl rats in vivo,
      prompted us to explore conditions that enable osteoclasts to be formed in tl
      metatarsals in vitro. Coculture of neonatal tl metatarsals with CSF-1 alone
      produced no osteoclasts, but the addition of normal spleen and bone marrow cells
      and parathyroid hormone or 1,25-dihydroxyvitamin D produced osteoclasts in most
      cultures. Identical cultures of metatarsals from the CSF-1 deficient op/op mouse
      produced similar results. Within the contexts of the role of CSF-1 in
      osteoclastogenesis and the different biologic manifestations of osteopetrosis in
      these two mutations, we interpret these results to mean that other factors are
      required to restore osteoclast function completely in tl rats and op mice. Thus,
      experimental studies of these mutations are likely to provide new insights on
      both osteopetrosis and osteoclast biology.

PMID- 7626320
TI  - Bone mineral density of the total body and forearm in premenopausal black and
      white women.
AB  - This study was conducted to report and compare bone mineral density (BMD) of the
      total body and distal forearm, as measured by X-ray absorptiometry, in 65 black
      and 73 white premenopausal women between the ages of 20 and 40. The black women
      had higher current and recalled body weights, a higher percent body fat, and more
      pregnancies and births, were younger at menarche, and reported lower alcohol
      intakes than the white women studied. A smaller percent of the black women had
      experienced amenorrhea, and a higher percent had lived at southern latitudes.
      Smoking history and lifetime use of oral contraceptives were similar in the two
      groups. Total body BMD, adjusted for body mass index (BMI), was 5.9% higher in
      the black than in the white women [mean +/- standard deviation (SD): 1.230 +/-
      0.076 g/cm2 compared with 1.161 +/- 0.075; difference (95% confidence interval
      [CI95]: 0.068 (0.042, 0.095)]. Forearm BMD, adjusted for BMI, was 9.3% higher in
      the black women [mean +/- SD: 0.505 +/- 0.046 compared with 0.462 +/- 0.045;
      difference (CI95): 0.043 (0.027, 0.059)]. Adjustment for the other medical and
      lifestyle differences noted before had little effect on estimated BMD differences
      between the two groups.

PMID- 7626324
TI  - Similarities and differences between the effects of ipriflavone and vitamin K on
      bone resorption and formation in vitro.
AB  - The effects of ipriflavone and vitamin K on bone metabolism were examined using a
      culture system. Vitamin K1 and vitamin K2 (10(-7)M-10(-5)M) inhibited both the
      activation of mature osteoclasts and the formation of new osteoclasts without
      affecting the growth of progenitor cells in cultures of mouse unfractionated bone
      cells. The inhibitory effects of vitamin K on bone resorption were similar to
      those of ipriflavone and were not affected by the vitamin K antagonist warfarin.
      When ipriflavone was added to the culture medium in combination with vitamin K2,
      an additive inhibitory effect on bone resorption was observed. An additive effect
      was also observed in organ cultures of mouse calvaria. On the other hand,
      ipriflavone, but neither vitamin K1 nor vitamin K2, stimulated cellular alkaline
      phosphatase (ALP) activity on rat bone marrow stromal cells under culture
      conditions in which cells subsequently form mineralized bone-like tissue. Vitamin
      K1 and vitamin K2 also did not modulate the stimulatory effect of ipriflavone on
      the ALP activity of the cells. These results suggest that the inhibitory effects
      of vitamin K on bone resorption are similar to those of ipriflavone through
      mechanisms that may be independent of the gamma-carboxylation system, while the
      effects of vitamin K on osteoblast phenotype expression are different from those
      of ipriflavone.

PMID- 7626323
TI  - Role of extracellular calcium influx in EGF-induced osteoblastic cell
      proliferation.
AB  - This study investigated the effects of epidermal growth factor (EGF) on cytosolic
      calcium ([Ca++]i) levels in rat calvarial osteoblasts, the nature of the
      regulation of this event, and the role these EGF-induced [Ca++]i changes have in
      osteoblastic cell proliferation. EGF significantly increased [Ca++]i measured in
      fura-2-loaded, individual cells. This increase was related to extracellular
      calcium influx. Activation of protein kinase C(PKC) by pretreating the cells with
      phorbol esters blocked the EGF-induced increase in [Ca++]i. EGF failed to
      increase inositol trisphosphate levels measured by high performance liquid
      chromatographic analysis. However, it did increase inositol bisphosphate and
      inositol tetrakisphosphate production. The EGF-dependent increase in DNA
      synthesis was partially blocked by the addition of calcium channel blockers.
      Therefore, it appears that the mechanism of action of EGF-induced osteoblastic
      cell proliferation is mediated by changes in [Ca++]i primarily due to
      extracellular calcium influx.

PMID- 7626325
TI  - X-ray diffraction studies on the lattice perfection of human bone apatite (Crista
      iliaca).
AB  - The lattice perfection of human bone apatite (iliac crest of 117 individuals aged
      0-90 years) was systematically investigated by means of combined X-ray
      diffraction procedures--profile fitting and line-broadening analysis--correlated
      with age, sex, type of tissue (corticalis, spongiosa), and position (superior,
      middle, and inferior) for different crystallographic directions [length axis
      using reflection (002), basal plane by means of reflections (300), (210), and
      (310)]. Bone specimens within age group 0-30 were strongly affected by an
      increased crystallinity in the direction of the c-axis (domain size increasing by
      5-7 nm, strain decreasing respectively), whereas in the direction of the a-axis
      crystallinity decreased significantly (domain size shortening by 5-7 nm, strain
      increasing respectively) in correlation with some heteroionic substitutions
      within the apatitic structure. Within age group 30-80 a certain balance seemed to
      exist between processes of ordering and disordering such that statistically only
      a slight increase of crystallinity within the basal plane was observed. Age as
      main fixed effect was highly significant for all investigated parameters.
      Crystallinity was well correlated with type of tissue (corticalis, spongiosa) in
      the direction of the length axis of the bone crystallite.

PMID- 7626326
TI  - Physiologic, health and lifestyle factors associated with femoral neck bone
      density in older women.
AB  - Three hundred eleven women aged between 60 and 91 years (mean age 72.2) who were
      randomly recruited from the community underwent bone density assessments of the
      femoral neck. Two complementary multivariate techniques were used to assess the
      relationships between femoral neck bone density and a range of anthropometric,
      health, and lifestyle measures. Stepwise multiple linear regression analysis
      revealed age, weight, height, quadriceps strength, and lifelong smoking to be
      variables that independently and significantly explained part of the variance in
      femoral neck bone density within the group. Multiple logistic regression revealed
      that after adjusting for established predictors of bone mineral density, age,
      height, and weight, reduced quadriceps strength, lifelong smoking, and little
      childhood activity were significantly associated with low bone density (< 0.70
      g/cm2), whereas superior quadriceps strength, nonsmoking, and high levels of
      current physical activity were significantly associated with high bone density (>
      0.84 g/cm2). In contrast, current calcium intake was not significantly associated
      with bone density. The study findings highlight possible public health
      initiatives for minimizing age-related femoral neck bone loss in older women.

PMID- 7626329
TI  - Bone mass in children: normative values for the 2-20-year-old population.
AB  - Normative values for bone mass were assessed for whole body bone mineral content
      (WBBMC), anterior-posterior and lateral lumbar spine, radius, femoral neck,
      trochanter, and Ward's triangle bone mineral density in 778 healthy children and
      adolescents (433 females and 345 males) from 2-20 years of age from Argentina.
      Bone mineral content was assessed by dual energy X-ray absorptiometry (DEXA)
      (Norland XR-26 HS with dynamic filtration). All subjects were Caucasian. WBBMC
      maximum mean value for girls was found to be in the 16-year-old group with
      difference between gender becoming significant in the 17-year-old (p < 0.05)
      group. The femoral neck, trochanter, and Ward's triangle BMD values in females
      increased until 14 years of age, with no significant difference between age
      groups older than 13. In males, no difference between age groups was seen in
      groups older than 16 years of age. The radius BMD showed a mild increment through
      infancy and adolescence in boys and girls. In lumbar spine, the gender
      differences were significant only in those groups over 16 years old, with boys
      showing a greater BMD than girls (p < 0.001). When Tanner stage was considered,
      the anova analysis showed in males that there were significant differences
      between stages (1-2, 2-3, and 4-5 (p < 0.01), but no differences between stages 3
      4 for all the sites. In females, there were significant differences between
      stages 1-2 and 2-3 (p < 0.01), but not between stages 3-4 and 4-5 for WBBMC,
      FNBMD and LSBMD.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7626327
TI  - Diverse actions of calcitonin gene-related peptide on intracellular free Ca2+
      concentrations in UMR 106 osteoblastic cells.
AB  - Calcitonin gene-related peptide (CGRP) was examined for its effects on
      intracellular free Ca2+ concentration ([Ca2+]i) in UMR 106 osteoblast-like cells.
      Cells loaded with the Ca2+ dye FURA-2 dose-dependently responded to CGRP (1-100
      nM) with transient two-fold increases in [Ca2+]i. An intracellular source for
      this Ca2+ transient was suggested by the failure of membrane depolarization with
      high extracellular K+ or acute depletion of extracellular Ca2+ ([Ca2+]e) with
      EGTA to attenuate this response. After cells were incubated for 45 min with 0.1
      mM extracellular Ca2+ to deplete intracellular Ca2+ stores, CGRP produced a 25
      30% decrease in [Ca2+]i rather than a transient increase. This calcium decrease
      was mimicked by membrane depolarization or by pinacidil, a specific activator of
      adenosine triphosphate (ATP)-sensitive potassium (KATP) channels, and blocked by
      glybenclamide, a specific blocker of KATP channels. Our data suggest that CGRP
      has diverse Ca2+ regulatory effects in UMR 106 cells, mobilizing Ca2+ from
      intracellular stores via classical signaling while possibly promoting cellular
      Ca2+ efflux or inhibiting uptake through voltage-dependent Ca2+ channels via KATP
      mediated hyperpolarization.

PMID- 7626328
TI  - Supplemented gamma-linolenic acid and eicosapentaenoic acid influence bone status
      in young male rats: effects on free urinary collagen crosslinks, total urinary
      hydroxyproline, and bone calcium content.
AB  - The effect of different ratios of the prostaglandin precursors gamma-linolenic
      (GLA) and eicosapentaenoic (EPA) acids on bone status in growing rats measured as
      a function of free urinary pyridinium crosslinks and hydroxyproline levels was
      investigated. Male Sprague-Dawley rats were weaned onto an essential fatty acid
      deficient diet and from their fifth week, different groups of rats received a
      balanced, semisynthetic diet, supplemented with different ratios of GLA:EPA
      supplied as a mixture of evening primrose oil (EPO) and fish oil (FO). Controls
      were supplemented with linoleic (LA; sunflower oil) and alpha-linolenic (ALA;
      linseed oil) acids (3:1) or a commercially available rat chow. Animals were
      terminated at 84 days and femur length, ash weight, calcium content, free urinary
      pyridinium crosslinks (Pyd and Dpyd), total hydroxyproline (Hyp), and creatinine
      levels measured. Free urinary Pyd and Dpyd are good indicators of bone status and
      they correlated well with Hyp. Pyd and Dpyd excretion were significantly
      decreased in the higher GLA:EPA dietary groups and correlated well (r = 0.7) with
      Hyp levels. Concomitantly, bone calcium content increased significantly in the
      same dietary groups. These results suggest that diet supplementation with
      relatively high GLA:EPA ratios are more effective in inhibiting bone resorption
      than LA:ALA.

PMID- 7626330
TI  - Patient decision-making in relation to extensive restorative dental treatment.
      Part II: Evaluation of a patient decision-making model.
AB  - A theoretical model was proposed and tested to evaluate some of the factors
      involved in patients' decisions to undergo extensive restorative dental
      treatment. This model incorporates aspects of the environment within which the
      decision occurred (the patient/provider relationship, social influence and the
      role of cues in initiating treatment) and internal values held by the individual
      (perceptions of value of and barriers to treatment). Value of treatment was
      measured using aesthetics, function, health motivation and self-esteem. Barriers
      to treatment included fears and anxieties about treatment, the costs of
      treatment, the time involved in obtaining treatment and access to care. Data were
      collected by mailed questionnaire from 188 patients at a North American state
      university dental school who had received over $1,500 of restorative dental
      treatment during 1990/91. Data were analysed using path analysis multiple
      regression. The most important determinant in the decision to undergo treatment
      was patient/provider relationship. As expected, barriers exerted an inverse
      effect upon the outcome and had twice the influence compared with the patients'
      perceived value of treatment. Cues and social influence were not shown to play a
      significant role in initiating restorative dental treatment.

PMID- 7626331
TI  - Improvements in cross-infection control in general dental practice.
AB  - A questionnaire about cross-infection control was sent to all GDPs in five FHSAs
      in the North Western Region. Replies came from 312 dentists, a response rate of
      74%. They worked in 185 practices, a response rate of 85%. Gloves were worn
      routinely by 86% of dentists and 80% of DSAs. Handpieces were autoclaved between
      patients in 77% of practices. Much however, remains to be improved. DSAs could be
      better protected if more ultrasonic cleaners were used, eye protection encouraged
      and heavy duty gloves were available for cleaning instruments. BDA guidelines
      were reported as being the most influential factor, though it would appear that
      the media did persuade many practitioners to use autoclavable handpieces and
      sterilise them after each use.

PMID- 7626332
TI  - Minor oral surgery 'specialisation' in general dental practice.
AB  - A practitioner with 4 years' hospital oral surgery experience undertook minor
      oral surgery procedures within a general dental practice over a 4-year period.
      The variety of work completed is shown. The National Health Service fees for the
      procedures indicate that a practice limited to minor oral surgery is both
      practically and financially viable when referral fees and x-rays are included.
      Differences in the types of procedure undertaken by visiting 'specialist'
      practitioners and 'specialist' practices is highlighted. A population of 310,000
      is suggested for a 'specialist' practice in minor oral surgery to be feasible.

PMID- 7626333
TI  - Extraction forceps for small hands.
AB  - This paper discusses the problems encountered by small handed dentists when
      extracting teeth using standard forceps. An alteration in the design of standard
      upper forceps is proposed which will be advantageous to small handed dentists.
      The new design is 'open bladed', that is, when the handles are closed the blades
      are manufactured to be 5 mm apart.

PMID- 7626335
TI  - MRI update.
AB  - The Management Research Initiative aims to encourage research in dental practice
      management. We hope that GDPs and dental teams will get involved either by
      looking at management issues in their own practice or by collaborating with other
      researchers. In this update we give details of research being carried out that
      will give GDPs evidence of what influences a patient's choice of dentist and how
      the changing role of the dentist as manager is affecting stress levels.

PMID- 7626334
TI  - Non-surgical periodontal therapy: essential and adjunctive methods.
AB  - The presence of bacterial deposits on teeth has been observed since the birth of
      microbiology but it has taken over 300 years to understand which elements of the
      various hard and soft dental deposits must be removed in order to arrest the
      destructive processes caused by the periodontal diseases. This article reviews
      the current state of knowledge regarding non-surgical periodontal therapy,
      including adjuncts such as mouthrinses and antibacterials and considers when
      other treatment modalities would be beneficial for the patient.

PMID- 7626336
TI  - Endodontic failure--a problem from top to bottom.
AB  - Endodontically treated teeth are susceptible to bacterial contamination through
      exposure to oral fluids. It is crucial, therefore, that restorations placed
      during and after root canal therapy protect the root canal from oral
      contamination. This paper highlights the clinical steps necessary to reduce the
      risk of contamination in root-filled teeth.

PMID- 7626337
TI  - Left handed GDPs.

PMID- 7626339
TI  - Left handed GDPs.

PMID- 7626338
TI  - Left handed GDPs.

PMID- 7626340
TI  - Left handed GDPs.

PMID- 7626341
TI  - Occupational stress in dentistry.

PMID- 7626342
TI  - Occupational stress in dentistry.

PMID- 7626343
TI  - Potential for antiviral therapy in the treatment of restenosis after angioplasty.

PMID- 7626344
TI  - Assessment of coronary microcirculation with myocardial contrast
      echocardiography: current and future clinical applications.

PMID- 7626345
TI  - Cellular mechanisms of cardiac hypertrophy.

PMID- 7626346
TI  - Effects of streptokinase in patients presenting within 6 hours of prolonged chest
      pain with ST segment depression.
AB  - BACKGROUND: The effects of streptokinase on the occurrence of a combined clinical
      outcome in patients presenting with recent chest pain and ST depression were
      investigated in view of the role of thrombus in the pathogenesis of acute
      ischaemic syndromes. METHODS: 112 patients aged < or = 75 years presenting within
      6 h of the last episode of ischaemic chest pain of least 20 min duration with >
      or = 1 mm ST depression were randomised in a double blind manner to receive
      either streptokinase 1.5 million units over 30 min (n = 57) or placebo (n = 55).
      The primary end point was the combination of death, frequency of myocardial
      infarction (defined as peak creatine kinase > 600 U/ml), need for angiography
      because of uncontrollable ischaemia, and an exercise test within 35 days showing
      > or = 1 mm ST depression at < or = 6 min. The secondary end points were safety,
      frequency of chest pain, readmission with myocardial infarction or unstable
      angina, or need for revascularisation between 35 days and 1 year. The severity of
      ST depression on presentation was analysed with respect to clinical outcome.
      RESULTS: The frequency of the combined hierarchical end point of death,
      myocardial infarction, early angiography, and a positive exercise test was 82%
      (47 of 57 patients) with streptokinase and 75% (41 of 55 patients) with placebo.
      There were four deaths, two in each group. 27 patients (47%) receiving
      streptokinase and 22 (40%) receiving placebo developed myocardial infarction. 11
      patients (eight streptokinase and three placebo) required coronary arteriography
      and subsequent revascularisation because of angina uncontrolled by medical
      treatment. 44 patients (22 in each group) had a positive exercise test. There
      were three further cardiac deaths (one streptokinase, two placebo), and three
      noncardiac deaths within 1 year. A conservative approach to intervention was
      adopted and over a period of 1 year 29 patients (26%) (13 streptokinase and 16
      placebo) underwent revascularisation procedures. Three patients (two
      streptokinase and one placebo) required transfusion. ST depression > or = 3 mm
      had 90% specificity but only 60% positive predictive value for myocardial
      infarction at presentation (P = 0.008, stepwise logistic regression). ST
      depression > or = 2 mm was predictive of death, late development of myocardial
      infarction, or a need for angiography (P = 0.02). CONCLUSION: Patients presenting
      with ischaemic chest pain and ST depression frequently develop myocardial
      infarction. Severe ST depression is predictive of an adverse outcome. The 35 day
      (3.6% cardiac and total) and 1 year mortality (8.9% total, 6.3% cardiac) are low
      with conservative management and expeditious revascularisation. Streptokinase
      treatment within 6 h of the last episode of pain does not seem to be beneficial.

PMID- 7626347
TI  - Left ventricular volumes, ejection fraction, and plasma proatrial natriuretic
      factor (1-98) after withdrawal of enalapril treatment initiated early after
      myocardial infarction. CONSENSUS II Multi-Echo Study Group.
AB  - OBJECTIVES: To assess whether the reduction in left ventricular dilatation after
      acute myocardial infarction obtained by early administration of angiotensin
      converting enzyme inhibitors depends on continuous treatment. DESIGN: Prospective
      observational and cross sectional study of withdrawal of randomised treatment
      with enalapril or placebo. PATIENTS: 106 patients on 6 months trial treatment
      after an acute myocardial infarction. MAIN OUTCOME MEASURES: Left ventricular
      volumes and ejection fraction as assessed by echocardiography and circulating
      proatrial natriuretic factor (1-98) before and 4-6 weeks after withdrawal of
      treatment. RESULTS: There were no significant changes (mean (SD)) in left
      ventricular systolic (0.7 (4.7) ml/m2) and diastolic (0.4 (6.6) ml/m2) volume
      indices, ejection fraction (-0.9 (6)%), and proatrial natriuretic factor (172
      (992) pmol/l) after withdrawal of enalapril. The significantly lower left
      ventricular volumes observed with 6 months of enalapril therapy after acute
      myocardial infarction, as compared with placebo, were maintained 6 weeks after
      drug withdrawal. CONCLUSION: The results show that the benefit of 6 months of
      enalapril treatment initiated early after myocardial infarction is maintained for
      at least 6 weeks after drug withdrawal, suggesting that the treatment effect on
      left ventricular structure is not reversed by changes in loading conditions
      caused by subsequent drug withdrawal.

PMID- 7626348
TI  - Plasma proatrial natriuretic factor (1-98) concentration after myocardial
      infarction: relation to indices of cardiac and renal function.
AB  - OBJECTIVES: (a) To assess the relation between plasma concentrations of proatrial
      natriuretic factor (1-98) and non-invasively derived indices of left ventricular
      systolic and diastolic performance and (b) to assess the potential confounding
      effect of renal function and age on this relation in patients with acute
      myocardial infarction. DESIGN: Cross sectional comparison of biochemical and
      echocardiographic indices of cardiac function. SETTING: Norwegian central
      hospital. PATIENTS: Sixty four patients with acute myocardial infarction. MAIN
      OUTCOME MEASURES: Relation between plasma proatrial natriuretic factor (1-98)
      concentrations and echocardiographic indices of left ventricular systolic
      function as assessed by univariate and multivariate linear regression analysis.
      Sensitivity and specificity of plasma proatrial natriuretic factor (1-98)
      concentration as a measure of left ventricular systolic and diastolic
      dysfunction. RESULTS: Plasma proatrial natriuretic factor (1-98) concentrations
      were significantly related to left ventricular ejection fraction (r = -0.33; P =
      0.008), age (r = 0.43; P < 0.001), and creatinine clearance (r = - 0.53; P <
      0.001). In a multivariate model left ventricular ejection fraction and creatinine
      clearance were both independently related to plasma values. The mean
      concentration of proatrial natriuretic factor (1-98) was significantly higher in
      patients with an ejection fraction of < 40% than in those with an ejection
      fraction of > or = 40% (1876 (1151) v 1174 (530) pmol/l; P = 0.03) and in
      patients with an abnormal transmitral E/A ratio ( < 0.65 or > 1.65, where E/A is
      ratio of peak early filling velocity to peak atrial component) compared with
      those with a normal ratio (1572 (895) v 1137 (523) pmol/l, respectively; P =
      0.02). When patients were subdivided according to the median concentration of
      proatrial natriuretic factor (1192 pmol/l) the sensitivity and specificity were
      89% and 56% respectively for detecting a left ventricular ejection fraction of <
      40% and 75% and 61% respectively for detecting an abnormal E/A ratio.
      Concentrations below the median had a negative predictive value of 97% in
      excluding an ejection fraction of < 40% and of 84% in excluding an abnormal E/A
      ratio. CONCLUSION: These results suggest that soon after myocardial infarction
      left ventricular ejection fraction and indices of renal function are
      independently related to plasma concentrations of proatrial natriuretic factor (1
      98). Plasma concentrations of proatrial natriuretic factor (1-98) seem to reflect
      renal and cardiac performance rather than specific haemodynamic variables
      assessed by noninvasive methods. Plasma proatrial natriuretic factor (1-98)
      measurements may be a useful screening tool to identify patients with normal
      cardiac function soon after myocardial infarction.

PMID- 7626349
TI  - Baroreflex sensitivity and cardiovascular mortality in patients with mild to
      moderate heart failure.
AB  - OBJECTIVE: To assess the influence of both sympathetic (plasma noradrenaline
      concentrations) and parasympathetic (baroreflex activation) tone on survival in
      patients with congestive heart failure. DESIGN: Invasive study with determination
      of parasympathetic activity and follow up for at least 4.5 years. SUBJECTS: 35
      patients with sinus rhythm and mild to moderate heart failure (New York Heart
      Association grades II-III) (mean age 53 (SD 3)). RESULTS: 20 patients whose
      hearts survived were compared with 15 patients whose hearts did not (12 died and
      three received transplants). The two groups differed significantly in terms of
      mean arterial blood pressure (98 (3) v 90 (3) mm Hg), heart rate (82 (2) v 93 (4)
      beats/min), and mean pulmonary artery pressure (24 (3) v 35 (2) mm Hg) (all P <
      0.05), while cardiac index, stroke volume index, and right atrial pressures were
      not different. The survivors had significantly lower plasma renin activities (3.6
      (0.8) v 9.0 (3.6) angiotensin I/ml/h; P < 0.05) and tended to have lower
      noradrenaline values than non-survivors (170 (23) v 286 (74) pg/ml) at baseline.
      Baroreflex sensitivity was significantly lower in non- survivors than in
      survivors (1.3 (0.2) v 2.3 (0.3) ms/mm/Hg); P < 0.02). As the time of cardiac
      transplantation is dependent on complex logistical factors the three patients who
      received a transplant were excluded from the analysis of survival time. The risk
      of death in relation to baroreflex sensitivity at the median sensitivity of 1.48
      ms/mm Hg was calculated. Survival was significantly different (P < 0.04) between
      the resulting two groups; three of the 16 subjects with high baroreflex
      sensitivity died compared with nine of the 16 with a baroreflex sensitivity <
      1.48 ms/mm Hg. When systemic blood pressure, pulmonary artery pressure, stroke
      volume index, plasma noradrenaline concentrations, and baroreflex sensitivity
      were entered into a Cox proportional hazards regression, only systolic blood
      pressure and plasma noradrenaline values predicted survival (P < 0.001).
      CONCLUSIONS: Low vagal tone is correlated with a poor prognosis in patients with
      heart failure. Sympathetic tone measured as plasma noradrenaline concentration
      also contributed to survival. An additional contribution of vagal tone to
      survival could not be shown when sympathetic tone was considered simultaneously.
      This may be due to the inverse relation of sympathetic and parasympathetic tone
      and to the insensitivity of the multiple regression method to identify additional
      risk factors in small numbers of patients.

PMID- 7626350
TI  - Dynamic assessment of the electrocardiographic QT interval during citrate
      infusion in healthy volunteers.
AB  - OBJECTIVE: To investigate changes in the electrocardiographic QT interval during
      rapidly induced, sustained hypocalcaemia in healthy volunteers. DESIGN: Serial
      rate corrected QT measurements were made during and after a variable rate
      trisodium citrate infusion designed to "clamp" the whole blood ionised calcium
      concentration 0.20 mmol/l below baseline for 120 min. SUBJECTS: 12 healthy
      teetotallers aged 19- 36 years who were not receiving medication known to
      influence calcium homoeostasis. MAIN OUTCOME MEASURES: Whole blood ionised
      calcium concentration and QaTc intervals (onset of the Q wave to T wave apex
      divided by the square root of the RR interval). RESULTS: Mean (SD) ionised
      calcium concentration decreased from 1.18 (0.03) mmol/l preinfusion to values
      close to target (0.98 mmol/l) between 10 and 120 min. The QaTc interval
      lengthened from a baseline of 0.309 (0.021) to a maximum 0.343 (0.024) s0.5 at 10
      min before returning to a stable level from 15 to 120 min (0.334 (0.023) and
      0.330 (0.023) s0.5 respectively). The change from baseline of both variables
      expressed as a ratio (delta QaTc/ delta [Ca2+]) was greater during rapid
      induction of hypocalcaemia (at 5 and 10 min) than at other times during and after
      the infusion (P < 0.02). CONCLUSIONS: The disproportionate prolongation of QaTc
      interval during prompt induction of hypocalcaemia suggests rate dependency which
      can be represented by a hysteresis relation between (ionised calcium, QaTc)
      coordinates. This finding may have clinical implications.

PMID- 7626351
TI  - Increased markers of thrombogenesis in chronic atrial fibrillation: effects of
      warfarin treatment.
AB  - OBJECTIVE: To determine whether chronic atrial fibrillation is associated with
      abnormalities in plasma fibrinogen, von Willebrand factor (vWF) (a marker of
      endothelial disturbance), or fibrin D- dimer (a measure of fibrin turnover); and
      if so, whether such levels are related to haemodynamic disturbance (enlarged left
      atrium, poor left ventricular function) or existing treatment with warfarin or
      aspirin. To investigate the effects of introducing warfarin in patients with
      atrial fibrillation on fibrinogen and D- dimer levels. DESIGN: Cross sectional
      population sample controlled study and longitudinal study of patients undergoing
      anticoagulation. SETTING: District general hospital. SUBJECTS: 87 patients (44
      men and 43 women of mean (SEM) age 63.0 (1.0)) with chronic atrial fibrillation.
      At the time of the study, 37 were taking no antithrombotic medication (group 1),
      31 were taking warfarin (including two on warfarin and aspirin) (group 2) and 19
      were taking aspirin alone (group 3). They were compared with 158 population
      controls from a random population sample (the second Glasgow monitoring trends
      and determinants in cardiovascular disease study). As part of clinical treatment
      warfarin was introduced in 20 patients with chronic atrial fibrillation (14 men
      and six women of mean (SEM) (range) age 63.9 (2.35 (32-74) years). RESULTS:
      Plasma fibrinogen remained significantly increased in patients of group 1 (no
      antithrombotic medication) compared with that of the population controls (median
      difference 1.23 g/l; 95% confidence interval (CI) 0.88 to 1.62, P < 0.0001).
      There was also a significant increase in plasma D-dimer levels (median difference
      77 ng/ml; 95% CI 38 to 122, P < 0.01) and vWF (median difference 63 IU/dl; 95% CI
      38 to 89, P < 0.0001). There was no significant difference in plasma fibrinogen
      (median difference 0.14 g/l; 95% CI -0.44 to 0.77, P = 0.65) or vWF (median
      difference 3.5 IU/dl; 95% CI - 41 to 41, P = not significant in patients of group
      2 (warfarin treatment) compared with that of patients in group 1. Levels of D
      dimer were significantly lower in group 2 (median difference 90 ng/ml, 95% CI 39
      to 150, P < 0.0001) than in group 1. There were no significant differences in
      plasma fibrinogen (median difference 0.08 g/l; 95% CI - 0.52 to 0.77, P = 0.73),
      D-dimer (median difference - 34 ng/ml; 95% CI - 114 to 21.0, P = 0.25), or vWF
      (median difference 2%; 95% CI - 35 to 41, P = not significant) levels between
      patients of groups 1 and 3. There were no significant correlations between the
      coagulation indices and left atrial volume or ventricular function. There was a
      significant positive correlation between plasma fibrin D-dimer and vWF levels in
      patients of groups 1 and 3 (r = 0.52, P < 0.001). There was a significant
      reduction in median plasma fibrin D-dimer levels at 2 months after the
      introduction of warfarin (181 ng/ml v 80 ng/ml, P < 0.001), but no effect on
      plasma fibrinogen. CONCLUSIONS: Increased median plasma fibrinogen and vWF levels
      were found in patients with chronic atrial fibrillation. Plasma D-dimer levels
      were also increased in patients with chronic atrial fibrillation not receiving
      warfarin, suggesting increased intravascular thrombogenesis in such patients.
      Introduction of warfarin normalised circulating fibrin D- dimer levels,
      suggesting that warfarin treatment was effective in preventing excessive fibrin
      turnover, consistent with the antithrombotic effects of warfarin. These results
      suggest three possible thrombotic markers to assess patients with atrial
      fibrillation who are at high risk of thrombogenesis; D-dimer also merits
      assessment as a measure of reduction in thrombotic risk in patients receiving
      warfarin.

PMID- 7626353
TI  - Beta adrenoceptor density in the donor heart: a guide to prognosis?
AB  - BACKGROUND: Failure of the donor (graft) heart is the main cause of mortality in
      the first month after orthotopic cardiac transplantation. In a preliminary study
      marked downregulation of cardiac beta adrenoceptor density was found in
      apparently normal donor hearts of recipients who developed severe cardiac failure
      soon after implantation. Cardiac beta adrenoceptors are an important factor in
      the development of cardiac failure in the human heart. The aim of this study
      therefore was to determine whether fatal graft failure in the first month after
      transplantation is associated with downregulation of beta adrenoceptor density in
      the donor heart. PATIENTS AND METHODS: Right ventricular endomyocardial biopsy
      specimens were taken from consecutive adult donor patients immediately before
      implantation. A previously described radioligand binding method was used to
      determine beta adrenoceptor density in consecutive patients who developed fatal
      graft failure and died within 1 month of transplantation and in a group of
      control donors transplanted during the same period. RESULTS: Perioperative fatal
      graft failure developed in 13 patients. Forty one specimens from donor hearts
      that were transplanted into recipients who did not develop fatal graft heart
      failure formed the control group. There were no systematic differences in donor
      or recipient characteristics between the graft heart failure and control groups.
      In particular donor catecholamine requirement and recipient pulmonary vascular
      resistance did not differ between groups. Total beta adrenoceptor density was
      reduced in the fatal graft heart failure group compared with that in the controls
      (13.4 (7) fmol/mg v 21 (7) fmol/mg; P < 0.01). There was a positive correlation
      between beta adrenoceptor density in the donor heart and time to death in the
      graft heart failure group (r2 = 0.3, P < 0.05). The beta adrenoceptor binding
      affinity (Kd) did not differ between the graft failure group and the controls (47
      (6) pM v 44 (7) pM). CONCLUSION: The development of perioperative fatal cardiac
      failure after orthotopic cardiac transplantation is associated with
      downregulation of beta adrenoceptors in the donor heart before implantation.

PMID- 7626352
TI  - Expression of tumour necrosis factor alpha and accumulation of fibronectin in
      coronary artery restenotic lesions retrieved by atherectomy.
AB  - BACKGROUND: The formation of coronary artery neointima experimentally induced in
      piglets after cardiac transplantation is related to an immune-inflammatory
      reaction associated with increased expression of T cells and inflammatory
      mediators (tumour necrosis factor alpha and interleukin 1 beta) and upregulation
      of fibronectin. In vivo blockade of tumour necrosis factor alpha in rabbits after
      cardiac transplantation results in reduced neointimal formation. The objective of
      this study was to investigate the hypothesis that coronary restenosis after
      atherectomy or percutaneous balloon angioplasty is associated with a similar
      inflammatory cascade initiated by mechanical injury. METHODS: Specimens taken at
      coronary atherectomy were analysed from 16 patients. Nine had had the procedure
      performed twice, firstly, to remove a primary lesion, and secondly, to remove a
      restenotic lesion. Seven had percutaneous balloon angioplasty after removal of
      restenotic tissue. Coronary atherectomy specimens were analysed by
      immunohistochemistry for the presence of T cells, macrophages, major
      histocompatibility complex II, interleukin 1 beta, tumour necrosis factor alpha,
      fibronectin, and the receptor for hyaluronan mediated motility. RESULTS: The
      groups were clinically and angiographically similar with equivalent lumens before
      and after atherectomy. Restenotic lesions had increased expression of tumour
      necrosis factor alpha and fibronectin compared with the primary lesions (P < 0.05
      for both). There was also a trend towards a greater number of T cells and
      increased expression of interleukin 1 beta. CONCLUSIONS: Restenosis is associated
      with increased expression of tumour necrosis factor alpha and fibronectin,
      suggesting that an immune-inflammatory reaction probably contributes to
      neointimal formation and may represent a form of wound healing and repair
      secondary to mechanical injury.

PMID- 7626354
TI  - Ventricular tachycardia and exercise related syncope in children with
      structurally normal hearts: emphasis on repolarisation abnormality.
AB  - OBJECTIVE: To emphasize the importance of ventricular tachycardia associated with
      repolarisation abnormality in syncope associated with exercise. DESIGN:
      Retrospective analysis of data on children presenting with syncope between 1985
      and 1993. PATIENTS: 5 apparently normal children with recurrent exercise related
      syncope associated with electrocardiographically abnormal TU complexes. RESULTS:
      3 children were diagnosed as having an intermediate form of the long QT syndrome
      and catecholamine sensitive ventricular tachycardia because the abnormal TU
      complexes were associated with polymorphic ventricular tachycardia that was not
      typical of torsades de pointes. Tachycardia was induced by exercise in all
      patients and by isoprenaline in the one patient who was tested. One patient also
      had sinus node dysfunction. One child had incessant salvos of polymorphic
      ventricular arrhythmias and intermittent abnormal TU complexes suggestive of
      repolarisation abnormalities. The other had typical congenital long QT syndrome.
      Treatment was effective in three patients; two patients took a beta blocker alone
      and one took a beta blocker and low doses of amiodarone. One patient died
      suddenly, death being associated with sinus node dysfunction. In one patient with
      incessant ventricular arrhythmias treatment with a beta blocker, amiodarone, or
      Ic drugs was ineffective and always associated with proarrhythmia or syncope. He
      was not given further treatment and was asymptomatic despite having mild
      cardiomegaly. CONCLUSIONS: Ventricular tachycardia associated with repolarisation
      abnormality was an important cause of exercise related syncope in apparently
      normal children. TU complex abnormalities can be identified by repeated
      electrocardiography. beta Blockers are effective in preventing recurrent
      episodes. The role of amiodarone in this type of ventricular tachycardia needs
      further evaluation.

PMID- 7626355
TI  - Gender differences in left ventricle geometry and function in patients undergoing
      balloon dilatation of the aortic valve for isolated aortic stenosis. NHLBI
      Balloon Valvuloplasty Registry.
AB  - BACKGROUND: Gender differences in cardiac size have been described in normal
      humans and animals and in response to pressure overload. To examine the influence
      of gender on the left ventricular response to pressure overload, clinical,
      haemodynamic, and echocardiographic data were analysed in the 232 adults with
      isolated aortic stenosis enrolled in the Balloon Valvuloplasty Registry. METHODS
      AND RESULTS: There were 92 men (mean (SD) age 75 (11) years) and 140 women (79
      (9) years; P = 0.002). Women had similar symptoms (New York Heart Association
      class) but lower overall functional status than men (P = 0.008). Catheterisation
      data showed similar valve area indices (mean (SD) (0.30 (0.09) in men and 0.31
      (0.13) cm/m2 in women) but higher peak and mean gradients in women (peak 74 (30)
      v 63 (22) mm Hg; mean 61 (21) v 54 (18) mm Hg; both P < or = 0.01). On M mode
      echocardiography women had greater septal and posterior wall thickness but
      similar cavity diameter, after normalising dimensions to body surface area,
      resulting in higher relative wall thickness (0.60 (0.20) v 0.50 (0.15); P =
      0.0002). Left ventricular mass index was similar in women and men (166 (59) v 159
      (50) gm/m2 respectively), however, the prevalence of left ventricular hypertrophy
      according to sex specific criteria was 54% in men and 81% in women (P = 0.0001).
      Multiple logistic regression models that adjusted for age, functional status,
      fractional shortening, and left ventricular systolic pressure found the presence
      or absence of hypertrophy to be independently associated with gender (P < or =
      0.002). Left ventricular systolic function tended to be better in women, who had
      a higher cardiac index (2.5 (0.8) v 2.3 (0.6) 1/min/m2; P = 0.01), left
      ventricular peak systolic pressure (211 (36) v 192 (35) mm Hg; P = 0.0001), and
      echo fractional shortening (32 (13) v 28 (12)%; P = 0.05); however, these
      differences were reduced when patients with regional wall motion abnormalities
      were excluded. CONCLUSIONS: In this population of elderly patients undergoing
      balloon dilatation of isolated aortic stenosis, left ventricular chamber geometry
      was different in men and women. Because this was a selected population, gender
      should be further evaluated as a possible determinant of the cardiac adaptation
      to chronic pressure overload.

PMID- 7626356
TI  - Percutaneous balloon dilatation of the mitral valve in critically ill young
      patients with intractable heart failure.
AB  - OBJECTIVE: To assess the outcome of percutaneous balloon dilatation of the mitral
      valve in critically ill young patients with intractable heart failure. DESIGN:
      Retrospective analysis of all such patients presenting over a period of 4 years.
      PATIENTS: Of 432 consecutive patients undergoing percutaneous balloon dilatation
      of the mitral valve, 12 (mean age 29 years) with intractable heart failure were
      identified. Nine had severe pulmonary oedema and three had pulmonary oedema with
      severe right heart failure and hypotension. Three patients were pregnant and
      three required mechanical; ventilatory support. PROCEDURE: Percutaneous balloon
      dilatation of the mitral valve was performed using the Inoue balloon technique.
      The procedure was shortened by excluding full right study, cardiac output
      measurement, and left ventriculography. The mitral valve morphology and mitral
      valve area were determined before and after percutaneous balloon dilatation using
      cross sectional Doppler echocardiography. RESULTS: The procedure was technically
      successful in all patients. The mean (SD) echocardiographic value of the mitral
      valve area increased from 0.7 (0.1) to 1.4 (0.2) cm2 with a concomitant reduction
      in pulmonary artery systolic pressure (Doppler) from 81 (17) to 50 (7) mm Hg.
      There was a significant clinical improvement in all patients. The mean (range)
      fluoroscopy time for the procedure was 6.9 (1.7-14.1) min. During follow up (mean
      10 months) nine patients were in New York Heart Association (NYHA) functional
      class I, one was in class II, one under NYHA elective mitral valve replacement,
      and one, who refused elective surgery, died suddenly at home. CONCLUSION:
      Percutaneous balloon dilatation of the mitral valve can be performed as a life
      saving procedure in critically ill patients with mitral stenosis, as even a
      modest increase in valve area in these patients produces gratifying clinical
      improvement.

PMID- 7626357
TI  - Architecture of atrial musculature in humans.
AB  - OBJECTIVE: To investigate the gross arrangement of the principal muscular bundles
      of the two atria, and to suggest how it may contribute to contraction and spread
      of atrial excitation. DESIGN: A prospective analysis based on anatomical
      examination of adult human hearts. SETTING: A national heart and lung institute
      and a tertiary referral centre for cardiac disease. MATERIAL: 9 normal postmortem
      human hearts. METHODS: Dissection of atrial muscles with macrophotography.
      RESUltS--The atrial walls consist of circumferential and longitudinal muscular
      bundles, the former being arranged at the base of the atria with the latter
      predominating in the parietal walls. The muscular bundles in the right atrium are
      larger than those in the left. The main muscles forming the right atrial wall are
      the terminal crest and terminal pectinate muscles. The terminal crest, the most
      obvious muscle, is arranged longitudinally with its pectinate muscles connecting
      to the musculature of the atrioventricular vestibule. No structure resembling the
      terminal crest is seen in the left atrium. Instead the left atrial wall is
      composed of intermingled series of muscles, chief of these being the interatrial
      band and the septoatrial bundle. The former is arranged circumferentially at the
      atrial base, while the latter is mainly longitudinal. The wall of the right
      atrium is not of uniform thickness because of the presence of the terminal crest
      and its pectinate muscles on its internal surface. By contrast, the left atrial
      wall is much more uniform and its average thickness is greater than that of the
      right atrium. The rim of the oval fossa is the most important muscular structure
      on the septal surface and is formed by the infolded atrial walls. The other
      principal muscles of the atria attach to it, so that the rim provides mechanical
      support for overall movement of the atrial walls. Comparison of the gross
      arrangement of the atrial musculature with earlier echocardiographic measurements
      showed that this arrangement of the muscle explains movement of the
      atrioventricular ring and overall atrial contraction, and provides a suitable
      substrate for preferential conduction. CONCLUSION: The anatomical features of the
      atrial musculature explain the known facts concerning atrial contraction and
      preferential conduction.

PMID- 7626358
TI  - Comparison of three dimensional echocardiographic findings with anatomical
      specimens of various congenitally malformed hearts.
AB  - OBJECTIVE: To compare the reconstructions obtained by three dimensional
      echocardiography with the anatomical specimens used to generate the
      echocardiograms. DESIGN: The heart specimens were immersed in a water bath and
      imaged with a 5 MHz echocardiographic transducer mounted into a scan frame which
      allowed the transducer to travel a total distance of 4.4 cm in steps of 0.25 mm.
      The transducer records a tomographic slice at each incremental level thus
      producing 176 parallel slices of the heart to form the dataset. Reconstruction of
      the anatomical structures of the heart in a three dimensional format is achieved
      by means of different grey scales. MATERIALS: 72 specimens of either normal or
      various congenitally malformed hearts. RESULTS: Good quality echocardiographic
      pictures were obtained, permitting three dimensional reconstructions in each
      heart. The cardiac chambers and valves could be displayed in a three dimensional
      format which accurately displayed the internal anatomy of the specimens. No
      artefacts, such as spurious septal defects, were produced in specimens with
      intact septums. The atrioventricular valvar leaflets, however, appeared thicker
      in the images than they were in the specimens. CONCLUSIONS: Three dimensional
      echocardiography accurately displays the anatomy of normal and congenitally
      malformed hearts.

PMID- 7626359
TI  - Early complications of permanent pacemaker implantation: no difference between
      dual and single chamber systems.
AB  - OBJECTIVE: To evaluate the incidence of intraoperative and early postoperative
      complications (up to two months after implant) of endocardial permanent pacemaker
      insertion in all patients under-going a first implant at a referral centre.
      METHODS: Prospective evaluation of all endocardial pacemaker implantation
      procedures performed from April 1992 to January 1994 carried out by completion of
      standard audit form at implant. Patients' demographic data, medical history,
      details of pacemaker hardware used, and any complications were noted. Follow up
      information was also collected prospectively onto standard forms at pacemaker
      outpatient clinic. SETTING: United Kingdom tertiary referral cardiothoracic
      centre. PATIENTS: 1088 consecutive patients underwent implantation of their first
      endocardial permanent pacemaker from April 1992 to January 1994. Implant and
      follow up data were available for 1059 (97.3%) patients at analysis. The median
      (range) age was 77 years (16-99); 51.2 % were male. RESULTS: Dual chamber units
      were implanted in 54.1% of patients, single chamber atrial in 5.2%, and
      ventricular in 40.7%. A temporary pacing lead was present at implant in 22.9% of
      patients. Most (93.6%) implants were performed via the subclavian vein. Immediate
      complications were rare: eight (0.8%) patients developed pneumothorax requiring
      medical treatment and 11 (1.0%) an insignificant pneumothorax. There was no
      significant difference in the pneumothorax rate for dual chamber (DDD) compared
      with single chamber systems. Arterial puncture without sequelae was documented in
      2.7% of attempts at subclavian vein cannulation. A total of 35 patients (3.3%)
      required reoperation; the reoperation rate for dual chamber (3.5%) was similar to
      that for single chamber (3.1%) systems. Electrode displacement (n = 15, 1.4%) was
      the most common reason for reoperation. Atrial lead displacement (n = 10, 1.6% of
      atrial leads) was significantly more common than ventricular lead displacement (n
      = 5, 0.5% of ventricular leads, P = 0.047). There was no difference in electrode
      displacement rates for dual (1.6%) compared with single (1.2%) chamber systems.
      Pacemaker pocket infection led to reoperation in 10 patients (six dual, four
      single chamber, P = not significant) and was significantly more common in
      patients who had a temporary pacing lead in place at implant (2.9%) than in those
      who did not (0.4%, P = 0.0014). Five patients (0.5%) required reoperation for
      generator erosion (two dual, three single chamber, P = not significant). and a
      further five for drainage of haematoma or a serous fluid collection (three dual,
      two single chamber, P = not significant). Complications that did not require
      reoperation were also rare. Undersensing occurred in 10 patients (0.9%). Atrial
      undersensing (n = 8) was significantly more common than ventricular undersensing
      (n = 2, P = 0.017). All patients were successfully treated by reprogramming of
      sensitivity. Superficial wound infection was treated successfully with
      antibiotics in nine patients (six dual, three single chamber, P = not
      significant). Three patients with DDD generators developed sustained atrial
      fibrillation: two required reprogramming to VVI mode and one required
      cardioversion. CONCLUSIONS: Permanent pacing in a large tertiary referral centre
      with experienced operators carries a low risk. Infection rates are low, < 1%
      overall but significantly higher in patients who undergo temporary pacing before
      implantation. Lead displacement and undersensing are more likely to occur with
      atrial than ventricular leads. The overall complication rate for dual chamber
      pacing, however, is no higher than for single chamber pacing.

PMID- 7626360
TI  - National perspective of acute coronary care in the Republic of Ireland.
AB  - OBJECTIVE: To assess the use of acute coronary care facilities in the Republic of
      Ireland with regard to case mix, patient characteristics, mortality and factors
      associated with mortality, time intervals to admission, utilisation of
      thrombolysis, and risk factor profiles. DESIGN: A 1 week prospective census of
      all hospitals admitting acute coronary cases. These comprised 23 coronary care
      units (CCU) and 17 combined coronary care/intensive care units (CCU/ICU). Data
      were collected by standardised methods on each new patient "upon whom a cardiac
      monitor was placed". RESULTS: Acute coronary heart disease was confirmed in 185
      (44.9%) of 412 patients. Of these 109 (26.4%) had a confirmed myocardial
      infarction and 76 (18.4%) unstable angina. Women were significantly older than
      men in all groups. Of those with proven acute coronary heart disease, 42.6% were
      current smokers, 23.1% were aware of having a raised cholesterol concentration,
      and 42.3% gave a history of prior hypertension. Only 44% were transported by
      ambulance. Median delay time from the onset of symptoms to admission was 6 h in
      Dublin and 4 h elsewhere. 34.9% of patients with a confirmed myocardial
      infarction received thrombolysis. Mortality of patients with myocardial
      infarction CCU/ICU at 7 days was 10.9 %. CONCLUSIONS: There is potential for
      considerable improvement in the management of coronary heart disease in the
      Republic of Ireland through a reduction in delay times to admission to hospital,
      increased use of thrombolytic treatment, and intensification of advice on primary
      and secondary risk factors.

PMID- 7626361
TI  - Atheroembolism in an endomyocardial biopsy from a cardiac transplant recipient
      after coronary angioplasty.
AB  - A case of a coronary atheroembolism after coronary angioplasty was detected by
      routine myocardial biopsy six years after cardiac transplant. The patient had had
      three balloon angioplasties within a five week interval for symptomatic
      accelerated coronary artery disease. Histological examination clearly identified
      atheromatous debris in a small intramyocardial artery with a secondary
      inflammatory response. This complication of angioplasty has been identified at
      necropsy in association with new myocardial infarction. It is unusual to identify
      this complication in a survivor, and in a case in which there was no clinical
      evidence of myocardial infarction. Myocardial biopsy samples a relatively small
      amount of myocardium, and this case suggests that coronary atheroembolism may not
      be an uncommon complication of angioplasty.

PMID- 7626362
TI  - Head-up tilt testing: the balance of evidence.

PMID- 7626363
TI  - Insulin resistance, high prevalence of diabetes, and cardiovascular risk in
      immigrant Asians.

PMID- 7626364
TI  - Quality of life in heart failure treated with enoximone.

PMID- 7626365
TI  - Responses of plasma concentrations of A type natriuretic peptide and B type
      natriuretic to alacepril, an angiotensin-converting enzyme inhibitor, in patients
      with congestive heart failure.

PMID- 7626366
TI  - Nitrates and severe aortic stenosis.

PMID- 7626367
TI  - The relationship of nutritional copper to the development of postmenopausal
      osteoporosis in rats.
AB  - Factors that influence tissue copper concentration include age, diet, hormones,
      and pregnancy. In this study we altered diet independently, hormone (estrogen)
      independently, and various combinations of diet and hormone in animals of the
      same age to study the effects of ovariectomy complicated with dietary copper
      deficiency; a deficiency that has been demonstrated to cause bone defects.
      Sprague-Dawley rats were placed on various combinations of copper deficient or
      enriched diets before and/or after ovariectomy to determine if copper deficiency
      aggravated osteoporosis and if return to a copper-adequate diet alleviated it. In
      this study, ovariectomy did induce an osteopenia that was characterized by
      decreased trabecular bone. This osteopenia was slightly more severe with copper
      deficiency, but was not necessarily alleviated by the return of normal copper
      levels to the diet.

PMID- 7626368
TI  - The role of cadmium in the peroxidative response of kidney to stress.
AB  - Since the kidney is a main target for cadmium, its accumulation in the kidney
      tissue by increasing peroxidative damage make the kidney functions vulnerable to
      stress. For this reason, the effect of cadmium-induced peroxidative damage to
      kidney responses to stress was investigated in this study. Two-month-old albino
      rats receiving 15 micrograms/mL containing Cd drinking water for 30 d were
      exposed to restraint and cold stress for 6 h, and their responses were compared
      with those of unstressed counterparts. Lipid peroxidation was found to be
      significantly higher in the cortical portion of kidney in cadmium-exposed rats
      than that of unexposed animals. The mean thiobarbutyric acid reactive substance
      (TBARS) level rose from 211.6 +/- 64.2 to 303.4 +/- 46.4 nmol/g protein (p <
      0.01). Six hours of cold and restraint stress caused an elevation in the cortical
      TBARS level in control animals without affecting its level in cadmium-exposed
      rats. Despite unaltered cortical TBARS, its medullar levels increased
      significantly in cadmium-exposed rats because of stress. These results suggested
      that cadmium accumulation in the kidney increases the susceptibility of medulla
      against peroxidative damage. However, further functional studies are necessary to
      explain the role of cadmium in the stress-induced deterioration of medullar
      functions.

PMID- 7626369
TI  - Characterization of a cadmium-zinc complex in lettuce leaves.
AB  - Vegetable food contributes a higher amount of daily cadmium (Cd) intake in humans
      than food of animal origin. The bioavailability of plant Cd depends on the
      content of plant zinc (Zn). The mechanism by which increased plant Zn lowers the
      intestinal absorption of plant Cd could be mediated by changes in the chemical
      speciation of Cd or Zn in plant edible tissues, including Zn-induced
      phytochelatin synthesis. To test this hypothesis we investigated the chemical
      speciation of Cd and Zn in leaf extracts of lettuce grown under 10 microM of Cd
      accompanied by 0.32 or 31.6 microM Zn in nutrient solution. Gel filtration
      chromatography of the low- or high-Zn leaf extracts yielded a major low molecular
      weight Cd-Zn complex that eluted at similar elution volume. Compared to low-Zn
      leaf extracts, high-Zn leaf extracts contained a higher proportion of Zn
      incorporated into high molecular weight components, and higher content of the
      amino acids Cys, Gly, Gly, and Asp in the low molecular weight Cd-Zn complex. The
      peptides isolated by high performance liquid chromatography (HPLC) of the Cd-Zn
      complex from the low- or high-Zn leaf extracts did not have an amino acid
      composition identical to phytochelatins. We concluded that 1. Sequestration of Cd
      or Zn via phytochelatin does not occur in leaves of lettuce containing levels of
      those metals representatives of Zn-Cd or Cd-only contaminated crops; and 2.
      Higher Cys, Glu, Gly, and Asp content in high-Zn than low-Zn leaves could lower
      Cd absorption in animals fed high-Zn crop diets, by enhancing metallothionein
      synthesis or changing Cd or Zn speciation in the animal gut.

PMID- 7626370
TI  - Effects of zamic as a means for zinc supplementation in growing children.
AB  - We investigated the effects of zinc supplementation in case of moderate growth
      retardation in which GH treatment could not be used. Zamic (ZA, an association
      containing arginine, L-methionine, and zinc; from Aguettant pharmaceuticals) was
      compared with arginine aspartate (AA) (5 g) in a crossover randomized trial (6 mo
      of each treatment at random order over 1 yr). We present preliminary results of
      24 children who completed the study (3 girls, 21 boys, age 9-13 yr). Subjects had
      to be prepubertal, with no GH deficiency diagnosed. In 15 subjects growth
      velocity was lower than 5 mm/mo: In this case ZA improved growth velocity (rising
      from 3.105 +/- 0.229 to 5.4 +/- 0.69 mm/mo p < 0.01), whereas the effect of AA
      was not significant. The increase in growth velocity was higher with ZA (+2.44 +/
      0.657 mm/mo) than AA (+0.438 +/- 0.450 mm/mo) p < 0.05. These results suggest
      that ZA is more efficient than AA, consistent with the hypothesis that zinc needs
      are increased in those children in this period of life.

PMID- 7626371
TI  - Comparison of three different methods for measurement of tissue platinum level.
AB  - We attempted to make a comparison of three methods for tissue platinum; atomic
      absorption spectrometry (AAS), inductively coupled plasma atomic emission
      spectrometry (ICP-AES), and inductively coupled plasma mass spectrometry (ICP
      MS). The determination limits were 0.05 ng/mL on ICP-MS, 50 ng/mL on ICP-AES, and
      200 ng/mL on AAS, and the recovery rates were 97.7 +/- 6.9% on ICP-MS, 69.0 +/-
      3.0% on ICP-AES, and 102.4 +/- 4.0% on AAS, respectively. Platinum was detected
      by ICP-AES and ICP-MS in human vertebrae, but the level was higher by ICP-AES
      than by ICP-MS. In the mouse kidney treated with cisplatin, platinum was detected
      by ICP-MS, but not by ICP-AES. As cadmium gives the absorption peak close to
      platinum, cadmium was measured together with platinum by ICP-AES in the
      vertebrae. From these, ICP-MS is the most sensitive for measurement at tissue
      platinum. The sensitivity of ICP-AES looks worse for measuring the tissue
      platinum, and it is necessary to take care of the contaminant of metals,
      especially cadmium. AAS is not suitable for measurement of tissue platinum as in
      the vertebrae and kidneys, because platinum was not detectable by AAS.

PMID- 7626372
TI  - Uptake and distribution of sodium selenite in rat brain tumor.
AB  - Eighteen weanling male Wistar rats with brain gliomas were divided into three
      groups, which received 0., 2.0, 5.0 ppm selenium (Se) in their drinking water.
      The accumulation and retention of selenium in the brain bearing tumor was
      investigated. Significantly higher concentrations of Se were observed in tumor
      tissue than normal brain tissue after exposure to sodium selenite. Tumors were
      observed in the 2.0 micrograms/g selenium group. The difference in selenium
      concentration between the tumor tissue and contralateral normal brain tissue was
      not influenced by the weight of brain or body, and water consumption. We observed
      that selenium accumulated in tumor tissue more than in normal brain tissue.

PMID- 7626373
TI  - Phosphate-loading test influences on endurance-trained volunteers during
      restriction of muscular activity and chronic hyperhydration.
AB  - The purpose of this investigation was to determine whether negative phosphate
      balance, which is developed during hypokinesia (a decreased number of walking
      steps/d) could be reversed with daily supplementation with phosphate, fluid, and
      salt (FSS). The studies on hypokinesia (HK) were performed for 364 d on 30
      endurance-trained male volunteers in the age range of 23-26 yr, with an average
      maximum oxygen uptake, MOU, of 65 mL/kg min. All subjects were divided into three
      equal groups: Ten volunteers were placed on a continuous regime of exercise of
      14.4 km/d at 10,000 steps/d and served as controls. Ten volunteers were subject
      to continuous HK without FSS and were considered as the hypokinetic subjects
      (HS). The remaining subjects were under continuous HK and FSS and were considered
      as the hypokinetic, hyperhydrated subjects (HHS). The three groups were on a diet
      that averaged 2620 cal/d and contained 1.7 g calcium, 1.6 g phosphate, and 5.6 g
      sodium chloride. For simulation of the hypokinetic effect, the HS and HHS groups
      were kept continuously under 2.9 km/d (3000 walking steps/d) for the duration of
      the study. Prior to exposure to HK, all volunteers were on the same exercise
      regime as the controls. During a 60-d pre-HK period and during the remainder of
      the study, phosphate-loading tests, urinary and plasma phosphate concentrations
      were performed in all subjects. In the HHS group, plasma phosphate concentration
      and urinary excretion of phosphate were decreased, while in the HS group these
      values increased after phosphate loading. Based on our results, we concluded that
      chronic hyperhydration and phosphate supplementation may be used to minimize
      phosphate losses in endurance-trained volunteers during prolonged restriction of
      muscular activity.

PMID- 7626374
TI  - Kinetic analysis of 75selenium uptake by mitochondria of germinating Vigna
      radiata of different selenium status.
AB  - Earlier studies in our laboratory demonstrated the beneficial role of Se in Vigna
      radiata, a Se-deficient legume, during germination, as reflected in growth
      related parameters and specific uptake of 75Se. Uptake of Na2(75)SeO3, added in
      vitro by mitochondria isolated from seedlings germinated in control (without Se),
      and Se-supplemented groups (0.5, 1.0, and 2.0 ppm Se) indicated a proportional
      increase in the uptake with added Na2(75)SeO3, in concentrations up to 25 microM.
      The uptake of 75Se, increased linearly with time up to 15 min and a definite
      efflux followed at 30 min. The results were indicative of cooperative effects
      during Se transport. Kinetic analyses of the uptake of 75Se during time intervals
      of 15 and 30 min were carried out both in the whole mitochondria and the
      mitochondrial protein fractions. Graphical analyses using Lineweaver-Burk plot,
      Hill plot, log [v] vs log [A] and Scatchard plot confirmed the existence of
      negative cooperativity during 75Se uptake. Hill coefficient (nH) values were
      estimated to be around 0.7-0.8. Scatchard plots for 75Se uptake were biphasic,
      suggesting the probable presence of two classes of binding sites. The number of
      high and low affinity binding sites were estimated to be around 4-7 and 26-30
      nmol/mg protein, respectively. Studies with mitochondrial respiratory inhibitors
      indicated about 10-20% of the total 75Se uptake to be energy dependent.
      Inhibition of 75Se uptake by about 60-70% by sulfate and sulfite (5-25 microM)
      implies the involvement of dicarboxylate port in Se transport. A decrease in the
      uptake of 75Se by 40-60% effected by CdCl2, HgCl2, mersalyl, and NEM confirmed
      the interaction of thiols in the process. Evidence for the regulatory nature of
      75Se uptake by mitochondria of V. radiata emerges from the present study.

PMID- 7626375
TI  - Effect of lead on lipid peroxidation in liver of rats.
AB  - The present study was undertaken to understand the biochemical mechanisms of lead
      toxicity in liver. We observed a significant accumulation of lead in liver
      following lead treatment, resulting in accentuation of lipid peroxidation.
      Concomitant to the increase in lipid peroxidation, the activities of antioxidant
      enzymes, viz., superoxide dismutase, catalase, glutathione peroxidase, and
      glutathione reductase, were significantly inhibited. A decrease in reduced
      glutathione with a simultaneous increase in oxidized glutathione was observed
      following lead exposure, resulting in a reduced GSH/GSSG ratio. These results
      indicate that lead exerts its toxic effects by enhancing peroxidative damage to
      the membranes, thus compromising cellular functions.

PMID- 7626376
TI  - Effect of cuprofilin on experimental atherosclerosis.
AB  - The effect of Cuprofilin, a newly synthesized C.(II)-chlorophyll complex, was
      assessed in rats with experimental atherosclerosis. The study was focused on
      changes in serum cholesterol, lipids, and triglycerides concentration as well as
      on serum and abdominal aorta Cu and Zn values. It has been ascertained that after
      90 d in animals fed a rich lipid diet there was a statistically significant
      increase in serum cholesterol, triglycerides, and lipid concentration (p < 0.01).
      A significant augmentation of serum Cu values (p < 0.01) accompanied by a marked
      lowering of the same element in abdominal aorta (p < 0.01) was also found, as
      compared to the results registered in the control group. However, Cuprofilin,
      administered for 90 d in the group of animals with experimental atherosclerosis,
      significantly decreased the serum cholesterol, triglycerides, and serum lipid
      values (p < 0.01), increased copper content in aortic tissue (p < 0.01) and
      lowered serum copper concentration (p < 0.01) as compared to the untreated group.
      Moreover, in the aorta of administered animals the lipid infiltration has been
      demonstrated to be significantly diminished vs the untreated group.

PMID- 7626377
TI  - Second malignancies associated with doxorubicin.

PMID- 7626378
TI  - Hepatitis B vaccine: still has its problems.

PMID- 7626380
TI  - Clinical versus laboratory tumor lysis syndrome in children with acute leukemia.
AB  - Renal and metabolic complications of tumor lysis syndrome (TLS) were recognized
      frequently in the 1960s and 1970s. Strategies were designed to prevent TLS. We
      conducted a retrospective chart review study to identify the current TLS risk in
      children with acute leukemia. Children were considered to have "laboratory tumor
      lysis syndrome" (LTLS) if two of the following metabolic changes occurred within
      4 days of the start of chemotherapy: a 25% increase in serum phosphate,
      potassium, uric acid, or blood urea nitrogen levels, or a 25% decline in serum
      calcium concentration. Clinical TLS (CTLS) was defined as LTLS plus a serum
      potassium level higher than 6.0 mmol/L or acute renal failure. Twenty-one of 30
      children developed LTLS; one developed CTLS. Absolute blast count, pretreatment
      white blood cell count, pretreatment lactic dehydrogenase, and sex or tumor DNA
      index did not correlate with the development of LTLS. LTLS is still frequent in
      children undergoing chemotherapy for acute leukemia; CTLS, however, is much less
      common.

PMID- 7626381
TI  - Simultaneous occurrence of viral-associated hemophagocytic syndrome and
      Langerhans cell histiocytosis: a case report.
AB  - Langerhans cell histiocytosis (LCH) is a class I histiocytosis characterized by
      the presence of the pathologic Langerhans cell, an unique histiocyte. In contrast
      to LCH, class II histiocytosis is characterized by the proliferation of
      mononuclear phagocytes other than Langerhans cells and includes sinus
      histiocytosis with massive lymphadenopathy, viral-associated hemophagocytic
      syndrome, and familial hemophagocytic lymphohistiocytosis. Until now, these two
      classes have been considered separate, if related, entities. We report a 10-month
      old girl who presented with pyrexia, hepatosplenomegaly, an eczematous skin rash,
      anemia, thrombocytopenia, and a markedly elevated serum IgG and IgM antibody
      level to cytomegalovirus. Histologic proof of both hemophagocytosis in the liver
      and bone marrow and LCH in the skin was obtained at presentation. The clinical
      course and response to treatment over 6.5 years is recorded. Although the
      etiology of both class I and class II histiocytosis remains unknown, we speculate
      that the monocytic/macrophage disorder, as well as the LCH, were both triggered
      by virus or viral-related monokines secreted by activated macrophages.

PMID- 7626379
TI  - Impact of childhood leukemia on family planning.
AB  - Clinical experiences have indicated that family planning is affected by childhood
      leukemia. To investigate this issue, 130 mothers and fathers of 68 families with
      a long-term disease-free survivor were studied using interviews and
      questionnaires concerning the effects of childhood cancer on family planning. In
      one third of the families, either one or both partners reported that their
      child's disease affected their reproductive planning in various ways. The most
      extreme variations included having completed the family before diagnosis but
      still having another child versus not having completed the family before
      diagnosis but refraining from further progeny. More than half of the affected
      families refrained from having further offspring, delineating psychological
      motives for their decision. For parents whose family planning is affected by
      their experiences with childhood leukemia, the decision-making process is an
      extra burden. Therefore we advocate that support for the parents of a child with
      cancer should include counseling on progeny, in which both genetic and
      psychological information should be provided.

PMID- 7626382
TI  - Partial nephrectomy in well-responding stage I Wilms' tumors: report of three
      cases.
AB  - We report on 3 of 21 stage I Wilms' tumor patients with tumor volumes of 190,
      890, and 1300 mL, respectively, who responded dramatically to preoperative
      chemotherapy according to the Austrian/Hungarian Wilms' Tumor Study 89 by tumor
      volume reductions to 20%, 23%, and 13%, respectively. Radical resection of the
      tumors with renal preservation was achieved in all patients. Postoperative
      studies did not show any functional deficit in the preserved kidney. The patients
      have been in complete remission for 26, 33, and 60 months, respectively. Our
      preliminary results indicate that tumor resection should be feasible in patients
      with good responding stage I Wilms' tumors.

PMID- 7626383
TI  - Congenital hypoplastic anemia in six patients: unusual association of short
      proximal phalanges with mild anemia.
AB  - Six congenital hypoplastic anemia (CHA) patients from five families who have been
      followed from 2 months to 28 years are presented. Mild hypoplastic anemia in a 13
      year-old girl was associated with clinodactyly of the fifth finger on both hands,
      shortness in the proximal phalanges on all fingers, and syndactyly between the
      second and third toes and short fourth toe on the right foot. These
      abnormalities, except for clinodactyly, have not been reported previously in CHA.
      In one of the five families genetic transmission was thought to be autosomal
      dominant since both the father and the son had the disease. Therapy with
      corticosteroids was initiated in all patients at the ages of 3.5 months to 13
      years. Complete or near-complete recovery of anemia was obtained.

PMID- 7626384
TI  - Fatal fat embolism in a patient with sickle-beta+ thalassemia.
AB  - We describe a case of an adolescent with sickle-beta+ thalassemia who developed
      fatal fat embolism syndrome. After presenting with bone pain, the patient
      developed mental status changes, hypoxemia, and died following cardiorespiratory
      arrest.

PMID- 7626385
TI  - Ataxia telangiectasia and lymphoma: an indication for individualized chemotherapy
      dosing--report of treatment in a highly inbred Arab family.
AB  - Ten of 18 children in a highly inbred Arab kindred suffered from either ataxia
      telangiectasia (AT) or a variant syndrome consisting of ataxia, microcephaly, and
      congenital cataract (AMC). Four of the nine afflicted children were treated in
      our unit when they developed lymphomas (both Hodgkin's and non-Hodgkin's
      including Burkitt's). They were given chemotherapy (either standard COMP or low
      dose ABV/CVPP). The children with non-Hodgkin's lymphomas died of sepsis after
      receiving full-dose COMP. Low-dose ABV/CVPP brought about a 20-month remission in
      one child with nodular sclerosing Hodgkin's lymphoma and both AT and AMC, but she
      developed a preleukemic syndrome and her parents refused further treatment; she
      too died. A fourth child, also with nodular sclerosing Hodgkin's lymphoma, is
      currently in complete remission after ABV/CVPP. Treatment of lymphomas in
      patients with AT is extraordinarily difficult and has potential side effects so
      grave as to necessitate careful monitoring and individualized protocols.

PMID- 7626386
TI  - Hepatitis B vaccination in children with cancer.
AB  - Between September 1991 and April 1993 the hepatitis B vaccination with
      recombinant hepatitis B vaccine was administered in 41 cancer patients following
      first diagnosis. All patients were under 16 year of age, with negative hepatitis
      B virus (HBV) serology and normal hepatic function. They received 40 micrograms
      of vaccine by injection into the deltoid muscle at 0, 1, and 2, months, with a
      fourth dose planned at the 4th month for nonresponders. At 1 year a booster dose
      was given. All the patients began vaccination within 1 month following diagnosis,
      and periodic serologic follow-up was performed immediately after each vaccination
      and also in the 6th, 9th, and 12th months after vaccination. Patients with
      production of anti-HBs at a titer equal to or greater than 10 mIU/L were
      considered seropositive. The seroconversion rates were 12.4%, 21.9%, 41.0%, and
      48.7% after the first, second, third, and fourth monthly doses, respectively.
      Seroconversion rates were 56.0% at 6 months, 67.5% at 9 months, and 70.5% at 12
      months. Geometric mean antibody titers were 212 and 373 mI U/L at 9 and 12
      months, respectively. No serious side effects were observed. HBV vaccination is
      recommended for pediatric cancer patients.

PMID- 7626387
TI  - Epidural spinal cord compression as an initial symptom in childhood acute
      lymphoblastic leukemia: rapid decompression by local irradiation and systemic
      chemotherapy.
AB  - We treated an 11-year-old girl with spinal cord compression near an epidural
      tumor. Bone marrow examination confirmed the diagnosis of acute lymphoblastic
      leukemia (ALL). To reduce the compression we treated her immediately with high
      dose dexamethasone and vincristine administered intravenously along with local
      irradiation. Three days later, radiation was discontinued because magnetic
      resonance imaging showed that the spinal cord compression was reduced. Complete
      remission has continued without evidence of neurologic sequelae for more than 3
      years since diagnosis. Rapid reduction of the blasts resulted in tumor lysis
      syndrome, which was treated with conventional management and additional diuresis
      without hemodialysis. Epidural spinal cord compression in childhood ALL can be
      treated effectively with systemic chemotherapy and local radiotherapy without
      laminectomy.

PMID- 7626388
TI  - Acute lymphoblastic leukemia in a girl treated for osteosarcoma.
AB  - Acute lymphoblastic leukemia (ALL) was diagnosed in a 13-year-old girl who had
      been treated previously for osteosarcoma of the left distal femur (23 months
      after her first cancer onset and 12 months after the end of treatment). The
      patient started chemotherapy for ALL and achieved complete remission; she is in
      continuous complete remission 5 years after the diagnosis of secondary ALL and 7
      years after the onset of osteosarcoma.

PMID- 7626389
TI  - Interferon alfa therapy in an infant with juvenile chronic myelogenous leukemia.
AB  - We describe an infant with juvenile chronic myelogenous leukemia (JCML), the
      diagnosis of which was made by the characteristic clinical and hematologic
      findings. The absence of a related HLA-compatible donor for bone marrow
      transplantation coupled with the awareness that chemotherapy is usually
      ineffective prompted our decision to treat the patient with lymphoblastoid
      interferon-alpha [alpha(Ly)-IFN]. During the 26-month course of treatment with
      alpha(Ly)-IFN an incomplete regression of hematologic and clinical findings was
      achieved. The above results, along with the easy administration and absence of
      considerable side effects, suggest that alpha(Ly)-IFN may be a useful therapeutic
      tool in patients affected by JCML awaiting bone marrow transplantation.

PMID- 7626390
TI  - Complicated pulmonary aspergillosis with pneumothorax and pneumopericardium in a
      child with acute lymphoblastic leukemia.
AB  - Invasive aspergillosis is a fungal infection that is being observed increasingly
      in immunocompromised patients due to the use of more aggressive chemotherapeutic
      regimens. To our knowledge, no case of pneumothorax and pneumopericardium
      associated with invasive pulmonary aspergillosis has been reported to date. High
      dose amphotericin B (1 to 1.5 mg/kg/day) is the treatment of choice, although
      severe side effects, especially hypokalemia, are very common. Itraconazole is
      considered to be a therapeutic alternative for invasive pulmonary aspergillosis
      in immunocompromised patients. A rare combination of pneumothorax and
      pneumopericardium associated with systemic aspergillosis in a child with acute
      lymphoblastic leukemia is described. Treatment with low-dose amphotericin B and
      itraconazole achieved complete resolution of the foregoing complications.

PMID- 7626391
TI  - Hematologic recovery after marrow-ablative chemotherapy and peripheral blood stem
      cell transplantation in children.

PMID- 7626392
TI  - Pyridoxine-responsive sideroblastic anemia in four children.

PMID- 7626393
TI  - Efficacy of prolonged low-dose steroid treatment in a child with idiopathic
      hypereosinophilic syndrome: a case report.

PMID- 7626394
TI  - Anaphylactic reaction to high-dose methotrexate.

PMID- 7626395
TI  - Megadose methylprednisolone for chemotherapy-induced neutropenia in children with
      malignancy.

PMID- 7626396
TI  - Roles of retinoic acid receptors and of Hox genes in the patterning of the teeth
      and of the jaw skeleton.
AB  - Retinoic acid receptors and transcriptional factors encoded by Hox genes play key
      roles in vertebrate development and belong to an integrated functional network.
      To investigate the actual functions of these molecules during ontogenesis and in
      particular in the patterning of the cranial neural crest cells giving rise to the
      teeth and to the jaw bones, we have generated null mutant mice lacking functional
      retinoic acid receptors or Hox genes by gene targeting in embryonic stem cells.

PMID- 7626397
TI  - Antisense oligonucleotides: an experimental strategy to advance a causal analysis
      of development.
AB  - A variety of modified and unmodified oligonucleotides (ODNs) have been examined
      as antisense inhibitors of gene expression. Of particular interest has been the
      application of antisense inhibitory experimental strategies to advance a
      suggested causal relationship between signal transduction and inductive
      epithelial-mesenchymal interactions during mandibular morphogenesis, early tooth
      development, tooth enamel formation, lung branching morphogenesis, kidney, muscle
      and heart development. Epidermal growth factor (EGF), platelet-derived growth
      factor (PDGF), and a number of transforming growth factor beta (TGF-beta) isotype
      mediated signal transductions have been demonstrated to regulate inductive
      processes associated with significant processes in development including mouse
      molar tooth morphogenesis. Antisense strategies have also been useful in studies
      designed to associate a specific morphogen signal with homeobox (HOX) gene
      regulation in several embryonal carcinoma cell lines. The application and results
      from a number of antisense inhibitory strategies serve to support the utility of
      this experimental paradigm for future investigations of tooth development. This
      review discusses the experimental strategy, a number of technical issues and the
      rationale for future investigations of tooth development.

PMID- 7626399
TI  - The tooth as a model in organogenesis. An interview with Professor Harold C.
      Slavkin. Interview by Juan Arechaga.

PMID- 7626398
TI  - The amelogenin gene.
AB  - Amelogenin is a major protein constituent of the developing enamel matrix. This
      protein is now well characterized from the data of amino acid sequences which
      have been shown to be at a high degree of homology between all species
      investigated to date. The gene structure of this protein has been demonstrated
      and it is confirmed that there are two amelogenin genes, one on the X-chromosome
      and the other on the Y-chromosome in humans. The mapping of human amelogenin gene
      in the p22 region on the X-chromosome and the gene on the Y-chromosome was
      established. It has been confirmed that several types of X-linked amelogenesis
      imperfecta are caused by structural defects in the amelogenin gene on the X
      chromosome. The physiological importance of amelogenin in the enamel formation is
      suggested by the symptoms of this inherited disease in addition to inhibition
      experiments of amelogenin transcription and translation (Couwenhoven et al., J.
      Craniofac. Genet. Dev. Biol. 13:259-269, 1993; Diekwisch et al., Development
      117:471-482, 1993). Recently, an attempt to synthesize recombinant mouse
      amelogenin by E. coli was also undertaken (Simmer et al., Calcif. Tissue Int.
      54:312-319, 1994). The regulation of amelogenin expression is now under
      investigation (Chen et al., Dev. Dynamics 199:189-198, 1994) and the elucidation
      of this mechanism will contribute a great deal to the study of tooth development.

PMID- 7626400
TI  - The enamelin (tuftelin) gene.
AB  - This paper reviews the primary structure, characteristics and possible function
      of tuftelin/enamelin protein. It describes the distribution of tuftelin in the
      ameloblast cell and in the extracellular enamel matrix, employing high resolution
      protein-A gold immunocytochemistry. The chromosomal localization of the human
      tuftelin gene and its possible involvement in autosomally linked Amelogenesis
      Imperfecta, the most common hereditary disease of enamel, is also discussed.

PMID- 7626401
TI  - The chemistry of enamel development.
AB  - The central problems of enamel biochemistry are the mechanisms concerned with
      initiation and development of the mineral crystals, together with their
      architectural arrangement within the tissue. These processes are mediated by the
      extracellular matrix as well as the composition of the mineral itself. Initial
      mineral deposition occurs at the dentine surface, nucleated either by dentinal
      components or early enamel matrix, possibly non-amelogenin molecules. The early
      crystals are small in size and rich in magnesium and carbonate resulting in
      relatively poor crystallinity. This is in spite of the fact that fluoride is high
      at this stage. Crystal development includes a reduction in magnesium, carbonate
      and fluoride as crystals increase in length following the retreating ameloblasts
      from the dentine. The matrix acquires increasing concentrations of amelogenin and
      albumin. Prismatic structure begins to develop together with some growth of
      crystals in width and thickness. Degradation of amelogenin and non-amelogenin
      molecules generates a series of specific molecular fragments possibly concerned
      with modulating crystal growth and morphology and the creation of prismatic and
      interprismatic structures. Towards the end of secretion, matrix, now almost
      completely degraded, is replaced by fluid followed by massive crystal growth
      during maturation. Degradation of albumin also occurs at this stage, probably as
      a result of comprehensive destruction of molecules which might impair crystal
      growth. Selective acquisition of magnesium and fluoride at this stage may reflect
      the hydrated state of the tissue as well as cell changes. Fluid is displaced as
      crystals grow and the enamel acquires concentrations of mineral characteristic of
      mature tissue.

PMID- 7626402
TI  - Overview of morphological changes in enamel organ cells associated with major
      events in amelogenesis.
AB  - The formation and mineralization of enamel is controlled by epithelial cells of
      the enamel organ which undergo marked, and in some cases repetitive, alterations
      in cellular morphology as part of the developmental process. The most dramatic
      changes are seen in ameloblasts which reverse their secretory polarity during
      differentiation to allow for extracellular release of large amounts of proteins
      from plasma membrane surfaces that were originally the embryonic bases of the
      cells. Secreted enamel proteins at first do not accumulate in a layer but, in
      part, percolate into the developing predentin and subjacent odontoblast layer.
      Appositional growth of an enamel layer begins with mineralization of the dentin,
      and ameloblasts develop a complicated functional apex (Tome's processes) to
      direct release of matrix proteins, and perhaps proteinases, at interrod and rod
      growth sites. Once the full thickness of enamel is produced, some ameloblasts
      degenerate, and the surviving cells shorten in height and spread out at the
      enamel surface. They reform a basal lamina to cover the immature enamel, and
      continue producing small amounts of enamel proteins that pass through the basal
      lamina into the enamel. Ameloblasts also undergo cycles of modulation where
      apical invaginations enriched in Ca-ATPases and other enzymes are formed and shed
      on a repetitive basis (ruffle-ended/smooth-ended transitions). As this happens,
      apatetic crystals seeded earlier expand in volume by gradual layering of new
      mineral at the surfaces of the preformed crystals. Ameloblasts stop modulating
      when the crystals almost fill existing volume formerly occupied by protein and
      water.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7626403
TI  - Enamel free areas in rodent molars--ultrastructure of basement membrane in rat
      tooth germ.
AB  - At the cusp tip of rodent molar, there is a region of dentin without an enamel
      cap. This region is called enamel free area (EFA). The surface collagen
      arrangement has been reported to differ between the EFA and the dentin covered
      with the enamel (DCE). To clarify the cause of this difference, we observed the
      ultrastructure of the basement membrane and the distal ends of the inner enamel
      epithelium (IEE) in rats. At 20 days prenatal, distal ends of IEE were relatively
      flat on both the DCE and EFA. Ultrastructurally, there was no difference between
      the basement membranes. At newborn, no marked changes were observed in the
      morphology of the distal end of IEE on the DCE or the EFA, but aperiodic
      microfibrils perpendicular to basal lamina were denser and longer on the DCE than
      the EFA. At 2 days postnatal, cytoplasmic extensions from distal end of IEE
      penetrated through basal lamina, and these extensions were more developed on the
      DCE than the EFA. On the DCE, collagen fibrils ran into and between cytoplasmic
      extensions and were arranged perpendicular to the surface. On the EFA, collagen
      fibrils ran parallel to the surface, and few collagen fibrils ran into and
      between cytoplasmic extensions. These findings suggested that the differences in
      the collagen arrangement between the EFA and DCE are associated with the
      developmental state of aperiodic microfibrils in the basal lamina beneath IEE and
      the morphology of the distal end of IEE.

PMID- 7626404
TI  - The nature and functional significance of dentin extracellular matrix proteins.
AB  - Odontoblasts are responsible for formation of predentin, which is transformed to
      dentin when apatite crystals are formed and the fibrillar matrix becomes
      mineralized. Odontoblasts are specialized cells that synthesize and secrete a
      unique set of non-collagenous proteins (NCPs), as well as the collagenous matrix
      largely comprised of type I collagen. The NCPs consist of dentin specific and
      mineralized tissue specific proteins, as well as other proteins that are found in
      a variety of tissues. Three dentin specific proteins have been recognized to
      date: dentin phosphoprotein (DPP), also called phosphophoryn, AG1 (dentin matrix
      protein 1, Dmp1) and dentin sialoprotein (DSP). DPP appears to be made by
      odontoblasts and appears at the mineralization front within a short time. It may
      be secreted via odontoblastic processes. DPP binds to collagen and potentially
      initiates formation of apatite crystals. A second DPP function appears to be to
      bind to the 100 face of growing apatite crystals and to inhibit or slow their
      growth; thus, DPP may play a dual role by initiating mineralization and then
      affecting the crystal growth and perhaps the habit of the crystals. Although no
      function has been ascribed to AG1 or DSP, they should prove to be important
      markers for the odontoblast phenotype. A recent unique finding is that two
      separate genes appear to code for more than one DSP mRNA; other transcripts may
      result from differential splicing. Examples of mineralized tissue specific
      proteins expressed by osteoblasts as well as odontoblasts are bone sialoprotein
      (BSP) and osteocalcin. Some NCPs expressed by osteoblasts, odontoblasts and
      several other tissues include osteopontin (OPN) and the chondroitin sulfate
      containing proteoglycans, decorin and biglycan. We propose that characterization
      of odontoblasts in tissues and cultures should rely upon utilization of sets of
      markers for the above NCPs and their mRNAs. Similar approaches are commonly used
      in investigations on osteoblasts. Finally, dentin (like bone) contains other
      molecules such as growth factors, and serum derived proteins, found within the
      matrix; no functional significance has yet been placed upon this finding. Future
      experiments should focus upon the elucidation of the three dimensional structures
      of the collagenous fibrillar network and of the NCPs to determine the
      relationships to mineralization. The role played by odontoblasts in controlling
      extracellular events, such as by selective secretory routes, will require careful
      exploration.

PMID- 7626405
TI  - Focal c-fos expression in developing rat molars: correlations with subsequent
      intradental and epithelial sensory innervation.
AB  - The purpose of this study was to analyze the temporal and spatial patterns of
      expression of the inducible transcription protein Fos and the Fos-related
      antigens (Fra) in developing rat teeth. Immunoreactivity (IR) for Fos/Fra was
      analyzed at postnatal age 1-35 days. A transient gradient of Fos/Fra-IR was found
      in all the molars in the coronal odontoblasts along sites of dentinogenesis, with
      numerous cells and intense staining near the pulp horn tip, and fewer cells and
      less staining in mid-crown and cervical pulp. This gradient was well established
      in first molars of the one day old rats; it was first seen in second molars in
      the 2 day old rats; and it was found in third molars at 10 days. The Fos/Fra-IR
      was transient and faded after a few days. Rat molars have a tilted orientation so
      that maxillary molar crown cusps point in a posterior direction and mandibular
      crowns in the anterior direction. In each set of molars dentinogenesis was
      initiated along the side of each pulp horn closest to the gingival surface, i.e.
      anterior for maxillary crowns and posterior for mandibular crowns; and the
      Fos/Fra-IR first appeared next to those asymmetric sites. As the wave of
      dentinogenesis spread around the crown, it was accompanied by odontoblastic
      expression of Fos/Fra-IR that had decreasing intensity in mid- and cervical
      crown. Molar root pulp lacked Fos/Fra-IR, and incisor teeth only had
      odontoblastic and ameloblastic immunoreactivity in the 1 day old rats.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7626406
TI  - The early distribution and possible role of nerves during odontogenesis.
AB  - Neural crest cells migrate along specific pathways to reach the mandibular and
      maxillary arches where they condense under specific areas of the ectoderm which
      will give rise to the primary and permanent dentition. In the mouse, the
      trigeminal ganglion becomes evident on E9 and the superior cervical sympathetic
      ganglion E13. Several studies have suggested that nerves in the vicinity of the
      developing teeth could influence the surrounding tissues and initiate tooth
      development, whereas other investigators have suggested that tooth development
      will proceed without an intact innervation. Innervation of the dental papilla has
      been reported as early as the cap stage in human teeth using an antibody to PGP
      9.5. A large variety of putative neurotransmitters have been localized in the
      nerves of the dental pulp. Many of the putative neurotransmitters function in
      vasoregulation while others have unknown functions. A hypothesis is presented
      describing a possible signal transduction pathway between odontoblasts and nerve
      terminals.

PMID- 7626407
TI  - Neurotrophins in odontogenesis.
AB  - Neurotrophins (NTFs) are a family of structurally related proteins with specific
      effects on the developing nervous system and a wide range of non-neuronal
      differentiating cells. To date, four NTFs have been characterized: nerve growth
      factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3),
      and neurotrophin-4 (NT-4). To perform their biological effects, the NTFs must
      bind to appropriate receptors on the surface of responsive cells. High- and low
      affinity receptors for NTFs have been identified. The high-affinity receptors are
      members of the trk protein tyrosine kinase receptor family. The low-affinity
      neurotrophin receptor gp75NTFR is a common receptor for all NTFs. Here we
      summarize some of our previous findings on the expression patterns of NGF,
      gp75NTFR, TrkB, and TrkC in the developing molar tooth of the rat. Both NGF and
      gp75NTFR are localized in dental epithelium and mesenchyme but often their
      expression patterns differ. Concomitant expression of NGF and gp75NTFR in
      mesenchyme is correlated with odontoblast differentiation. The trkB and trkC
      receptors show distinct cell-specific expression patterns in developing tooth,
      suggesting that other NTFs, apart from NGF, may be involved in odontogenesis.
      These data demonstrate that NTFs participate in the cascade of molecular events
      that direct tooth development, and support the notion that NTFs may have multiple
      and distinct roles in dental tissues.

PMID- 7626410
TI  - The mechanisms and mediators of tooth eruption--models for developmental
      biologists.
AB  - Tooth eruption is a localized process in the jaws which exhibits precise timing
      and bilateral symmetry. It involves resorption and formation of bone on opposite
      sides of the erupting tooth and these activities depend on the dental follicle, a
      thin connective tissue investment of the developing and erupting tooth.
      Biochemical studies have shown that during eruption cells, proteins and enzymes
      change in the dental follicle and several growth factors and proteins known to
      accelerate or retard eruption have been identified. This review discusses these
      aspects of tooth eruption and proposes testable hypotheses and strategies that
      can make studies of tooth eruption new experimental opportunities for
      developmental biologists.

PMID- 7626409
TI  - From serum to the mineral phase. The role of the odontoblast in calcium transport
      and mineral formation.
AB  - Dentin may be considered as a calcified connective tissue and is in its
      composition as well as in its mode of formation closely related to bone. Dentin
      is formed by two simultaneous processes in which the odontoblasts are
      instrumental: the formation of the proteinaceous dentin matrix, and mineral
      crystal formation in this matrix. As part of this, the odontoblasts actively
      transport Ca2+ ions towards the site of mineral formation. The cells maintain a
      delicate intracellular Ca2+ ion balance by the concerted action of
      transmembraneous transport mechanisms, including Ca-ATPase, Na+/Ca2+ exchangers
      and calcium channels of the L-type, and possibly intracellular Ca(2+)-binding
      proteins. The net effect of this is a maintenance of a cytoplasmic sub-micromolar
      Ca2+ activity and an extracellular accumulation of Ca2+ ions at the
      mineralization front. In addition to the major matrix constituent, collagen, non
      collagenous macromolecules, such as dentin phosphoprotein (phosphophoryn), dentin
      sialoprotein, and proteoglycan, are synthesized by the odontoblasts and deposited
      in the matrix. Such polyanionic macromolecules are presumably responsible for the
      extracellular induction of hydroxyapatite crystals, but may also function to
      inhibit mineral growth and to regulate crystal size. Accordingly, it can be
      concluded that dentinogenesis comprises an interplay between several factors in
      the tissue, cellular as well as extracellular.

PMID- 7626408
TI  - Biomineralization during early stages of the developing tooth in vitro with
      special reference to secretory stage of amelogenesis.
AB  - In this survey we summarize data on mineralization of enamel mostly obtained in
      organ culture experiments in our laboratory. Historically, the enzyme alkaline
      phosphatase has been proposed to stimulate mineralization by supplying phosphate
      or by splitting away inorganic pyrophosphate PPi, a potent inhibitor of
      mineralization. Localization of alkaline phosphatase in developing teeth by
      enzyme histochemistry shows that cells of the stratum intermedium contain
      extremely high levels of alkaline phosphatase but secretory ameloblasts that are
      engaged in deposition of the matrix and in transport of mineral ions lack
      alkaline phosphatase. The function therefore must be an indirect one, since no
      activity was seen at the site of enamel mineralization. We propose that the main
      function of alkaline phosphatase in the stratum intermedium is to transport
      phosphate or nutrients from blood vessels near the stratum intermedium into the
      enamel organ. Another function of the enzyme in stages of cell differentiation
      was deduced from inhibition experiments with the specific alkaline phosphatase
      inhibitor I- pBTM, showing that in tooth organ culture the enzyme may be involved
      in the generation of phosphorylated macromolecules from P ions originating from
      pyrophosphate. Calcium plays an indispensable role in enamel mineralization in
      vitro. Low calcium concentration in the culture medium prevented initial dentin
      mineralization and enamel formation. Moreover, differentiating ameloblasts did
      not become secretory, in contrast to odontoblasts that secreted a layer of
      predentin matrix. Variations in phosphate concentration in the culture medium do
      not seem to affect tooth organ cultures adversely during mineralization in vitro.
      Exposure to F-, however, has adverse effects on enamel mineralization depending
      on concentration and exposure time and produces a variety of disturbances. Many
      of the fluoride-induced changes in the enamel organ are reversible: young
      ameloblasts recover and resume secretion and mineralization of the fluorotic
      matrix when fluoride is removed from the medium. This recovery is enhanced when
      medium calcium levels are increased. Only the changes in the hypermineralized
      enamel remain irreversible. Thus, we hypothesize that fluoride induces a local
      hypocalcemia in the enamel fluid surrounding the enamel crystals by stimulating a
      hypermineralization of the pre-existing enamel crystals.

PMID- 7626411
TI  - Root formation.
AB  - This paper provides an overview of recent studies that have enhanced our
      understanding of the biological mechanisms that operate during root development.
      For the most part, these studies have been performed on rodents. As significant
      species differences have been shown to exist, this data cannot necessarily be
      extrapolated to the human model. The events associated with root odontoblast
      differentiation are reviewed in comparison to similar events in coronal
      odontoblast differentiation. Morphological as well as phenotypic differences are
      outlined and the inductive role of the epithelial root sheath is discussed. Both
      acellular and cellular cementum formation are reviewed highlighting morphological
      and phenotypic differences. The potential influence of the epithelial root sheath
      in the formation of both tissues is compared and contrasted. Finally, a
      discussion of the fate of the epithelial root sheath is presented with emphasis
      placed upon the possible roles of apoptosis and epithelium-mesenchymal
      transition.

PMID- 7626412
TI  - Contribution of 3-D computer-assisted reconstructions to the study of the initial
      steps of mouse odontogenesis.
AB  - The specific arrangement of mouse dentition in each dental quadrant (1-0-0-3) is
      supposed to result from the initiation of two independent dental laminae--one for
      the incisor and one for the three molars. In order to verify whether the adult
      mouse dental pattern really corresponds to the initial patterning, an analysis of
      development of the mouse antemolar part of the upper dental quadrant was
      performed in 10-13 day embryos using histological sections and computer-assisted
      3-D reconstructions. Six primary dental laminae contributed to the formation of
      the upper incisor anlage, which is, therefore, a structure of multiple origin. In
      contrast to the lower diastema, where only a low epithelial band extended
      mesially from the first lower molar in 12-13 day embryos, in the upper diastema a
      dental lamina existed interconnecting transiently the incisor and molar anlagen
      and giving rise to 3 distinct epithelial rudiments. The rudiments exhibited
      growth retardation and regressed after reaching a maximum at the bud stage. Our
      results showed a discrepancy between the embryonic and adult dental patterns in
      the mouse upper jaw. The specific arrangement of the mouse dentition implied a
      reduction of the embryonic dental anlagen, which was achieved either by their
      integration into the one incisor primordium or regression in the prospective
      diastema. Odontogenesis in the mouse upper jaw provides a model of hypodontia of
      evolutionary origin, which can be employed in molecular studies of the control
      mechanisms of initiation, spatial organization and specific morphogenesis of
      teeth.

PMID- 7626413
TI  - Morphogenesis of human tooth primordia: the importance of 3D computer-assisted
      reconstruction.
AB  - Three-dimensional reconstruction of embryological structures from histological
      serial sections is necessary when researching questions concerning formal
      development and mutual influences due to neighboring relationships. Graphical
      reconstructions can be performed by personal computers. In the present paper the
      need for 3D-reconstructions is explained, and examples showing the development of
      human dental primordia and their surrounding structures of specimens ranging
      between 18 and 64 mm CRL are presented. The contour-line plots that are provided
      by the software HISTOL are graphically reworked to anatomical drawings. Spatial
      impediment as one of the factors responsible for development of tooth form is
      discussed on the basis of the 3D-reconstructions.

PMID- 7626414
TI  - Ontogenetic aspects of dental evolution.
AB  - The evolution of dental ontogeny in the vertebrates is reviewed. Teeth probably
      originated as dermal structures, which secondarily spread to the mouth, where
      they became associated with bones. Tooth formation is a repetitive process,
      resulting in spatially separate units, and primitively it continued throughout
      life. Development of conical teeth commences at the tip and extends basally;
      folding of the basal lamina of the inner dental epithelium results in complex
      shapes, as in mammalian molars. Heterodonty, the divergent development of the
      teeth in a dentition, has evolved in a number of vertebrates, particularly
      mammals. Experimental analysis of dental development is still at an early stage,
      and the explanation of evolutionary changes in developmental terms is largely
      speculative Mammals are atypical vertebrates in many ways, and more studies of
      lower vertebrates, especially fishes, are needed.

PMID- 7626415
TI  - Ameloblasts and odontoblasts, target-cells for 1,25-dihydroxyvitamin D3: a
      review.
AB  - The basic features on the vitamin D endocrine system, synthesis of the main
      metabolite 1,25-dihydroxyvitamin D3 (1,25) and its genomic action mediated via
      the vitamin D receptor (VDR), are reviewed. Calbindin-D9k, calbindin-D28k and
      osteocalcin are presented as the most-extensively investigated vitamin D
      dependent calcium-binding proteins. The action of 1,25 on the basic process of
      proliferation and differentiation is introduced. Then, the basis of the systemic
      theory of vitamin D action on teeth (clinical and experimental data and the
      dissimilar distribution of VDR and of potential vitamin D-dependent proteins in
      dental cells) are exposed. Finally, the data obtained with calbindin-D9k,
      calbindin-D28k, osteocalcin and VDR, which supports the theory that ameloblasts
      and odontoblasts are target-cells for 1,25 is presented. As a perspective, a
      cross-survey of the 1,25 and tooth-related literature is proposed which may
      indicate potential target-genes for 1,25 in teeth as done previously for
      calbindins-D.

PMID- 7626416
TI  - Growth hormone and insulin-like growth factor-I in odontogenesis.
AB  - This review documents recent insights into the roles of growth hormone and
      insulin-like growth factor-I during tooth formation. Hereditarily growth hormone
      deficient Lewis dwarf rats and hypophysectomized rats have been used to document
      the influence of growth hormone on growth of the rat incisor and molar teeth in
      vivo. Cell population studies using bromodeoxyuridine labeling have shown that
      growth hormone administration to dwarf rats affects odontogenic cell
      proliferation in the incisor teeth. Immunohistochemistry, employing well
      characterized monoclonal antibodies directed against the hormone, its binding
      protein/receptor, the growth factor and its receptor, has enabled the location of
      these proteins to be mapped in the ontogenic sequences of ameloblasts,
      odontoblasts and cementoblasts. This mapping is consistent with the concept that
      differentiating odontogenic cells are targets for the hormone and that insulin
      like growth factor I is implicated as a secondary messenger in the same
      differentiating cell populations. The content of predentine and precementum
      matrices proteoglycans appears to be growth hormone-dependent. The proteoglycans
      implicated so far are rich in chondroitin sulphate and thus they may also be
      insulin-like growth factor I (sulphation factor)-dependent. Thus matrix synthesis
      may be what is principally affected by growth hormone in odontogenesis although
      no evidence of an effect on enamel matrix synthesis or proteoglycan content has
      yet been documented.

PMID- 7626417
TI  - Reactionary dentinogenesis.
AB  - Reactionary dentinogenesis is the secretion of a tertiary dentine matrix by
      surviving odontoblast cells in response to an appropriate stimulus. Whilst this
      stimulus may be exogenous in nature, it may also be from endogenous tissue
      components released from the matrix during pathological processes. Implantation
      of isolated dentine extracellular matrix components in unexposed cavities of
      ferret teeth led to stimulation of underlying odontoblasts and a response of
      reactionary dentinogenesis. Affinity chromatography of the active components
      prior to implantation and assay for growth factors indicated that this material
      contained significant amounts of TGF-beta 1, a growth factor previously shown to
      influence odontoblast differentiation and secretory behavior. Reactionary
      dentinogenesis during dental caries probably results from solubilization of
      growth factors, TGF-beta in particular, from the dentine matrix which then are
      responsible for initiating the stimulatory effect on the odontoblasts.
      Compositional differences in tertiary dentine matrices beneath carious lesions in
      human teeth have also been shown indicating modulation of odontoblast secretion
      during reactionary and reparative dentinogenesis.

PMID- 7626418
TI  - Basic mechanisms of cytodifferentiation and dentinogenesis during dental pulp
      repair.
AB  - Based on recent literature, the specific potential of mature pulp cells to
      differentiate into polarized cells able to elaborate reparative dentin is
      described. These odontoblast-like cells are distinguished, by morphological
      criteria, from the other matrix-formative cells involved in non-specific
      defensive mechanisms of dental pulp. The suitable tissue conditions and the
      normal cascade of reparative events, allowing initiation of dentinogenesis in
      sites of amputated pulp, are presented. This is followed by a review of current
      observations on specific dentinogenic events, induced in various culture systems
      or in intrapulpal sites of mature teeth by artificial bio-molecules or bio
      matrices. Data from these experiments are focused on the role of extracellular
      matrix molecules and growth factors in acquisition of the odontoblast-like cell
      phenotype and initiation of reparative dentinogenesis.

PMID- 7626419
TI  - Contributions of heterospecific tissue recombinations to odontogenesis.
AB  - Determining the functions of cell surface and substrate adhesion molecules during
      heterospecific tissue recombinations constitutes a significant problem in
      biology. The developing tooth organ provides a fine model to pursue this problem,
      especially in the context of instructive epithelial-mesenchymal interactions. The
      interpretation of many experimental heterospecific tissue combinations is
      difficult because of the complexity of the embryonic systems. According to some
      authors, the expressed phenotype corresponds to the genotype of the epithelium;
      on the contrary, other studies have demonstrated the leading role of the
      mesenchyme. The importance of cranial neural crest in tooth morphogenesis has
      been established. Lizard teeth maintain a continuous morphogenetic field
      throughout life (polyphyodont). These tissues can be considered as biological
      models and are ideally suited to study neural crest cell differentiation. Oral
      cavity of chick embryos show a rudiment resembling the dental lamina of
      amphibian, reptilian and mammalian embryos, though further odontogenic
      interactions between the epithelial and mesenchymal tissues are not operating.
      Some authors have suggested that genes involved in tooth formation, which have
      remained silent in birds for more than 200 million years, can be activated by
      appropriate signals. Chick epithelium combined with mesenchyme from mouse molar
      tooth produced dental structures with differentiated ameloblasts depositing
      enamel matrix. Quail neural crest combined with lizard dental bud showed quail
      cells with odontoblastic processes. Combinants (quail ectoderm-lizard papilla,
      and quail ectoderm-rabbit embryo papilla) showed differentiated chimeric-tooth
      like structures. However, controversy persists regarding the ability of avian
      epithelium to express the ameloblast phenotype and to secrete enamel
      protein.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7626420
TI  - Regulation of organogenesis. Common molecular mechanisms regulating the
      development of teeth and other organs.
AB  - Vertebrate organs develop from epithelial and mesenchymal tissues, and during
      their early development they share common morphological features. These include
      condensation of the mesenchymal cells and thickening, folding or branching of
      epithelial sheets. Sequential and reciprocal interactions between the epithelial
      and mesenchymal tissues play central roles in regulation of the morphogenesis of
      all organs. During recent years increasing amounts of molecular data have
      accumulated from studies describing developmental changes in expression patterns
      of molecules, as well as from functional in vitro studies and from the generation
      of transgenic mice. In this review article, we discuss common features in the
      molecular regulation that appear to be shared by the developing tooth and other
      organs. Several growth factors have been shown to act as inductive signals
      mediating epithelial-mesenchymal interactions in different organs. The early
      signals are proposed to regulate the expression of master regulatory genes, such
      as transcription factors. In early tooth germ, bone morphogenetic proteins BMP-2
      and BMP-4 regulate expression of the homeobox containing genes Msx-1 and Msx-2.
      These may specify early patterning of organs through regulation of molecules at
      the cell surface and the extracellular matrix, such as syndecan-1 and tenascin.
      Changes in cell adhesion and matrix remodelling, particularly in the organ
      specific mesenchyme and in basement membrane contribute to formation of
      mesenchymal cell condensations and to epithelial morphogenesis. Several growth
      factors and their receptors, particularly in the TGF beta-, FGF- and EGF-
      families, have been implicated in formation of mesenchymal condensates and in
      epithelial morphogenesis of many organs, including the tooth. It is apparent that
      molecules which regulate morphogenesis in different organs are potential
      candidate genes for congenital malformation syndromes in which several organs are
      affected.

PMID- 7626421
TI  - The experimental investigation of odontogenesis.

PMID- 7626422
TI  - Odontoblast differentiation.
AB  - Odontoblasts are post-mitotic, neural crest-derived, cells which overtly
      differentiate according to tooth specific temporo-spatial patterns and secrete
      predentin-dentin components. Neither the timing nor the molecular mechanisms of
      their specification are known and the problem of their patterning in the
      developing jaws is far from being solved. On the other hand, some significative
      strides were made concerning the control of their terminal differentiation.
      Fibronectin interacting with a 165 kDa, non integrin, membrane protein intervenes
      in the cytoskeletal reorganization involved in odontoblast polarization and their
      terminal differentiation can be triggered in vitro by immobilized members of the
      TGF beta family. Histological aspects and the transcriptional phenotypes
      (transcripts of TGF beta s, BMPs, msxs, IGF1, fibronectin, osteonectin, bone
      sialoprotein genes) are very similar in vivo and in vitro. In vivo members of the
      TGF beta super family secreted by preameloblasts, trapped and activated by
      basement membrane associated components, might initiate odontoblast terminal
      differentiation.

PMID- 7626423
TI  - Control of ameloblast differentiation.
AB  - This review highlights a number of advances towards understanding the sequential
      developmental cascade of events beginning in the oral ectodermally-derived
      odontogenic placode and culminating in the formation of the mineralized enamel
      extracellular matrix. Recent discoveries of growth factors, growth factor
      receptors and transcription factors associated with instructive epithelial
      mesenchymal interactions and subsequent controls for ameloblast cell
      differentiation are reviewed. The relationship between ameloblast cytology,
      terminal differentiation and biochemical phenotype are discussed. The tissue
      specific gene products characteristic of the ameloblast phenotype as well as
      their possible functions in formation of the enamel matrix are analyzed as well
      as the role of maturation-stage ameloblast cells in controlling enamel
      biomineralization. Finally, pathological conditions in which alterations in the
      ameloblast or specific gene products result in an abnormal enamel phenotype are
      reviewed. Clearly, the scientific progress achieved in the last few years
      concerning the molecular determinants involved in tooth development has been
      remarkable. However, there remains considerable lack of knowledge regarding the
      precise mechanisms that control ameloblast differentiation and enamel
      biomineralization. Anticipated progress continues to require increased
      international cooperation and collaborations as well as increased utilization of
      structural biology investigations of enamel extracellular matrix proteins.

PMID- 7626424
TI  - Dental mineralization.
AB  - Extracellular matrix components and cell-derived microstructures are implicated
      in mineralization processes which occur in dental tissues. The respective role(s)
      of collagenic and non-collagenic matrix components are reviewed: phosphorylated
      and non-phosphorylated proteins, proteoglycans and phosphpholipids. Space-filling
      amphiphilic molecules seem to play an important role in the preorganization and
      oriented deposition of calcium phosphate on structures serving more or less as
      passive support in dentine as well as in enamel.

PMID- 7626425
TI  - Worried to death. Interview by Dina Leifer.

PMID- 7626427
TI  - Just plain torture.

PMID- 7626426
TI  - Mental health: who's caring in the community?

PMID- 7626428
TI  - The use of steroids in asthma treatment.

PMID- 7626429
TI  - Changes in long-term mental health nursing.
AB  - This article tells the story of a group of people with severe and persistent
      mental disorder and the team who cared for them. A long-term research project
      into their needs and potential for changes in their care was conducted over 12
      years (1, 2). Its findings and innovations present examples of fundamental
      changes in care management that can be replicated elsewhere.

PMID- 7626430
TI  - The use of thinking tools in nursing.
AB  - Thinking is often taken for granted. But many people, including nurses, find that
      thinking and decision making are not the easiest of tasks. This article describes
      several ways of looking at thinking and outlines an easy-to-use technique that
      can help to improve the clarity and effectiveness of the way nurses think.

PMID- 7626431
TI  - A study of nurses' attitudes and quality of documents in computer care planning.
AB  - This article describes the introduction and development of a computerised care
      planning system at the Royal Hampshire County Hospital, Winchester - the first to
      be installed in a UK hospital. The research examined ward nurses' attitudes to
      the nursing process and the new care planning system before it was implemented,
      after three months and after one year. The quality of manual and computer care
      planning was also compared. Results showed that the majority of nurses were
      ambivalent about the nursing process and the proposed computer care plans. Three
      months after the new system was introduced, most nurses held negative attitudes,
      but after a year, attitudes, although still negative, showed a significant shift
      towards positive. The quality of care planning also improved significantly on the
      wards for which comparisons were possible.

PMID- 7626432
TI  - Images of nursing: registered sympathiser.

PMID- 7626434
TI  - Community care: let the clients choose their care.

PMID- 7626435
TI  - Carer's perspective: nursing your own.

PMID- 7626433
TI  - DC test: a testing time for the UKCC.

PMID- 7626436
TI  - The role of the nurse clinician in recurrent childhood headache.
AB  - At least four percent of children have recurrent headaches and migraine is the
      most frequent cause. Migraine and tension-type headaches may co-exist. A variety
      of factors, specifically dietary and stressors (at home and at school) have been
      recognized as triggers. We have reviewed the role of the Neurosciences Nurse
      Clinician in the management of children with recurrent headaches in our Pediatric
      Neurology Outpatient Clinic. About 150 children with headache are seen in our
      clinic annually. The Nurse Clinician complements the Pediatric Neurologist's role
      in the following ways: 1) Provides educational material and reinforces the benign
      nature of the headache (i.e. absence of serious cause); 2) Discusses potential
      role for triggers; 3) Provides and emphasizes the importance of keeping a
      headache diary: teaches children and caregivers how triggers may be identified;
      4) Makes follow-up telephone calls to determine changes in headache frequency/
      severity. This approach minimizes the need for prophylactic medication (less than
      25% of children we see require such treatment) and reduces the number of follow
      up visits to Pediatric Neurologist and other physicians, thus minimizing health
      care costs.

PMID- 7626437
TI  - Multiple sclerosis and self esteem.
AB  - A healthy conception of oneself is central to coping effectively with the day to
      day stresses of modern living. The onset of any neurological disease, with either
      actual visible deficits or potential future disability, threatens the integrity
      of that concept. This paper explores the concept of self-esteem. Alterations in
      self-esteem occur as a result of both internal or personal expectations and
      external or societal expectations. Manifestations of an altered self-esteem
      include self-negating verbalizations, reduced social interactions, lack of eye
      contact during interaction, and verbalization of feelings of guilt. While the
      focus of this paper will be the individual with Multiple Sclerosis, the concepts
      discussed are applicable across the spectrum of neurological disease.

PMID- 7626438
TI  - Dedicated short-stay spinal unit.
AB  - Prolonged waiting periods for patients with benign spinal surgical lesions led to
      the creation of a Dedicated Short Stay Spinal Surgical Unit. This unit was
      implemented in November, 1992, on a 29 bed Neuroscience Unit in a 1200 bed Acute
      Care Teaching Hospital. Considerations for implementation were many, including
      psychological impact of chronic pain for patients on prolonged waiting lists, the
      increased probability of permanent waiting lists, the increased probability of
      permanent neurological deficits, and the economic impact to patient, societal and
      hospital budgets. This paper will focus on explanation of the design of the unit,
      define the benefits and provide study results of the first 85 patients admitted
      to the unit.

PMID- 7626439
TI  - Management of multi organ donor.
AB  - The nurse is never "too prepared" when caring for the multiple organ donor. Some
      the many complications encountered include tachycardia, hyper/hypotension,
      hyper/hypothermia, diabetes insipidus, critical fluid and electrolyte imbalances,
      and hypoxia these are a result of brain stem herniation where the medulla
      herniates into the foramen magnum eventually leading to decreased cardiac output,
      impaired gas exchange, and impaired tissue perfusion if managed inappropriately.
      The challenge is on! Drug and fluid resuscitation have firm limits and guidelines
      which are of great importance to retrieval and transplant teams, and most of all,
      the recipient of the optimally perfused organ. Once the diagnosis of brain death
      is confirmed, the family is approached concerning their decision to donate.
      Psycho-emotional support of donor families is of upmost importance and you, the
      nurse, may call upon clergy, hospice, social services, or the transplant
      coordinator to assist. The organ procurement process involves the nurse, the
      transplant coordinator, and the physician. Since it is the nurse who will be
      "standing vigil" at the client's bedside, the very important role of anticipating
      the potential problems is crucial and this cannot be achieved unless we have a
      sound knowledge in the pathophysiology of central herniation.

PMID- 7626440
TI  - Proceedings of the IXth International Congress on Hormonal Steroids. Dallas,
      Texas, 24-29 September 1994.

PMID- 7626441
TI  - Regulation of apoptosis by steroid hormones.
AB  - Steroid hormones play major roles in regulation in growth, development,
      homeostasis, and cell death. Together with other hormones and growth factors,
      steroids regulate both the function and cellular composition of organs throughout
      the body. In this article we will discuss the mechanisms of steroid hormone
      regulated apoptosis. Emphasis will be placed on the effect of glucocorticoids on
      lymphoid cells.

PMID- 7626442
TI  - Role of the peripheral-type benzodiazepine receptor and the polypeptide diazepam
      binding inhibitor in steroidogenesis.
AB  - Steroidogenesis begins with the metabolism of cholesterol to pregnenolone by the
      inner mitochondrial membrane cytochrome P450 side-chain cleavage (P450scc)
      enzyme. The rate of steroid formation, however, depends on the rate of (i)
      cholesterol transport from intracellular stores to the inner mitochondrial
      membrane and (ii) loading of P450scc with cholesterol. We demonstrated that a key
      element in the regulation of cholesterol transport is the mitochondrial
      peripheral-type benzodiazepine receptor (PBR) and that the presence of the
      polypeptide diazepam binding inhibitor (DBI) was vital for steroidogenesis. We
      also showed that DBI, as the endogenous PBR ligand, stimulates cholesterol
      transport. In addition, DBI directly promotes loading of cholesterol to P450scc.
      We review herein our studies on the structure, function, topography and hormonal
      regulation of PBR and DBI in steroidogenic cells. Based on these data we propose
      a model where the interaction of DBI with PBR, at the outer/inner membrane
      contact sites, is the signal transducer of hormone-stimulated and constitutive
      steroidogenesis at the mitochondrial level. Hormone-induced changes in PBR
      microenvironment/structure regulate the affinity of the receptor. PBR ligand
      binding to a higher affinity receptor results in increased cholesterol transport.
      In addition, hormone-induced release (processing?) of a 30,000 Mw DBI
      immunoreactive protein from the inner mitochondrial membrane may result to the
      intramitochondrial production of DBI which directly stimulates loading of P450scc
      with cholesterol. Thus, in vivo, hormonal activation of these two mechanisms
      results in efficient cholesterol delivery and utilization and thus high levels of
      steroid synthesis.

PMID- 7626443
TI  - The murine 3 beta-hydroxysteroid dehydrogenase multigene family: structure,
      function and tissue-specific expression.
AB  - The classical form of the enzyme 5-ene-3 beta-hydroxysteroid
      dehydrogenase/isomerase (3 beta HSD), expressed in adrenal glands and gonads,
      catalyzes the conversion of 5-ene-3 beta-hydroxysteroids to 4-ene-3-ketosteroids,
      an essential step in the biosynthesis of all active steroid hormones. To date,
      four distinct mouse 3 beta HSD cDNAs have been isolated and characterized. These
      cDNAs are expressed in a tissue-specific manner and encode proteins of two
      functional classes. Mouse 3 beta HSD I and III function as 3 beta-hydroxysteroid
      dehydrogenases and 5-en-->4-en isomerases using NAD+ as a cofactor. The enzymatic
      function of 3 beta HSD II has not been completely characterized. Mouse 3 beta HSD
      IV functions only as a 3-ketosteroid reductase using NADPH as a cofactor. The
      predicted amino acid sequences of the four isoforms exhibit a high degree of
      identity. Forms II and III are 85 and 83% homologous to form I. Form IV is most
      distant from the other three with 77 and 73% sequence identity to I and III,
      respectively. 3 beta HSD I is expressed in the gonads and adrenal glands of the
      adult mouse. 3 beta HSD II and III are expressed in the kidney and liver with the
      expression of form II greater in kidney and form III greater in liver. Form IV is
      expressed exclusively in the kidney. Although the amino acid composition of forms
      I, III and IV predicts proteins of the same molecular weight, the proteins have
      different mobilities on SDS-polyacrylamide gel electrophoresis. This
      characteristic allows for differential identification of the expressed proteins.
      The four structural genes encoding the different isoforms are closely linked
      within a segment of mouse chromosome 3 that is conserved on human chromosome 1.

PMID- 7626444
TI  - Human prepubertal testicular cells in culture: steroidogenic capacity, paracrine
      and hormone control.
AB  - The neonatal human Leydig cell undergoes a transient period of activation during
      the first months of life. The biological significance of this activation is
      unknown. Furthermore, little is known about the hormonal regulation of this
      biological process, even though it coincides with an elevation of LH levels in
      serum. In order to study the function of human prepubertal testicular culture
      cells, obtained during the neonatal period, a method for maintaining primary
      culture cells (isolated from testes collected at necropsy) in culture was
      developed. Within 24 h after death, testes were collected from 1-36-month-old
      subjects. Subjects were divided into two age groups, based on the presence or
      absence of fetal Leydig cells: 1-7-month-old infants (group 1) and 12-36-month
      old children (group 2). Testes were digested with collagenase, and cells were
      seeded in multi-well dishes. Cells were grown in serum-free conditioned media
      supplemented with 5 mg/l vitamin C, 0.2 IU/l vitamin E and 10% fetal bovine serum
      for 2 days. Cells were then grown for an additional 4 days in serum-free media in
      the presence or absence of hLH (40 IU/l), hCG (135 IU/l), rh FSH (1.5 IU/l), rhGH
      (0.12 IU/l) or insulin (0.9 mumol/l). Concentrations of steroids in media were
      determined by RIA on day 6 of culture. In basal conditions cells of group 1 (n =
      11) secreted more testosterone, androstendione, 17-hydroxyprogesterone,
      progesterone and dehydroepiandrosterone (mean +/- SE: 6.76 +/- 1.86, 7.37 +/-
      1.82, 61.9 +/- 1.86, 5.75 +/- 1.74 and 8.51 +/- 3.23 pmol/10(6) cells/24 h,
      respectively) than cells of group 2 (n = 5) (2.95 +/- 1.15, 1.50 +/- 2.75, 1.44
      +/- 2.75, 0.78 +/- 1.74 and 3.23 +/- 1.32, respectively). Under hLH stimulation,
      cells of group 1 increased testosterone, androstendione and 17
      hydroxyprogesterone secretions (to 38.2 +/- 0.89, 13.5 +/- 1.17 and 51.7 +/-
      3.23), while progesterone secretion remained unchanged (2.82 +/- 1.20). Cell
      response to rhFSH and rhGH was similar to that of hLH. On the other hand, medium
      collected from cultures of cells isolated from a Sertoli cell tumor was able to
      stimulate testosterone secretion in subcultures of control testicular cells in a
      way similar to that of hCG. In conclusion, (1) these prepubertal human testicular
      cells can be maintained in primary culture for several days keeping their in vivo
      steroidogenic potential; (2) cells isolated from young infants can respond to hLH
      in culture; (3) response to rhFSH is probably mediated by a paracrine factor; (4)
      response to rhGH is observed in the absence of gonadotropins.(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 7626445
TI  - Molecular basis of human 3 beta-hydroxysteroid dehydrogenase deficiency.
AB  - The enzyme 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) catalyses an
      essential step in the biosynthesis of all classes of steroid hormones. Classical
      3 beta-HSD deficiency is responsible for CAHII, a severe form of congenital
      adrenal hyperplasia (CAH) that impairs steroidogenesis in both the adrenals and
      gonads. Newborns affected by 3 beta-HSD deficiency exhibit signs and symptoms of
      adrenal insufficiency of varying degrees associated with pseudohermaphroditism in
      males, whereas females exhibit normal sexual differentiation or mild
      virilization. Elevated ratios of 5-ene-to 4-ene-steroids appear as the best
      biological parameter for the diagnosis of 3 beta-HSD deficiency. The nonclassical
      form has been suggested to be related to an allelic variant of the classical form
      of 3 beta-HSD as described for steroid 21-hydroxylase deficiency. To elucidate
      the molecular basis of the classical form of 3 beta-HSD deficiency, we have
      analysed the structure of the highly homologous type I and II 3 beta-HSD genes in
      12 male pseudohermaphrodite 3 beta-HSD deficient patients as well as in four
      female patients. The 14 different point mutations characterized were all detected
      in the type II 3 beta-HSD gene, which is the gene predominantly expressed in the
      adrenals and gonads, while no mutation was detected in the type I 3 beta-HSD gene
      predominantly expressed in the placenta and peripheral tissues. The finding of a
      normal type I 3 beta-HSD gene provides the explanation for the intact peripheral
      intracrine steroidogenesis in these patients and increased androgen
      manifestations at puberty. The influence of the detected mutations on enzymatic
      activity was assessed by in vitro expression analysis of mutant enzymes generated
      by site-directed mutagenesis in COS-1 cells. The mutant type II 3 beta-HSD
      enzymes carrying mutations detected in patients affected by the salt-losing form
      exhibit no detectable activity in intact transfected cells, whereas those with
      mutations found in nonsalt-loser index cases have some residual activity ranging
      from approximately 1-10% compared to the wild-type enzyme. Although in general,
      our findings provide a molecular explanation for the enzymatic heterogeneity
      ranging from the severe salt-losing form to the clinically inapparent salt
      wasting form of the disease, we have observed that the mutant L108W or P186L
      enzymes found in a compound heterozygote male presenting the salt-wasting form of
      the disease, has some residual activity (approximately 1%) similar to that
      observed for the mutant N100S enzyme detected in a homozygous male patient
      suffering from a nonsalt-losing form of this disorder.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 7626446
TI  - Ectopic ACTH syndrome.
AB  - Ectopic ACTH syndrome represents a cancer-induced amplification of a property
      [proopiomelanocortin (POMC) peptides production] normally present in the cells
      from which the cancer originated but with aberrant posttranslational processing
      of POMC resulting in a greatly elevated secretion of ACTH precursors. The classic
      ectopic ACTH-producing tumors described in the 1960s were highly malignant but
      more recently slowly growing tumors such as carcinoids are reported with
      increasing frequency. Clinical features of patients with ectopic ACTH were
      analyzed, including biochemical abnormalities, plasma ACTH, cortisol and urinary
      steroids. Dynamic tests such as high-dose dexamethasone suppression, metyrapone
      and ovine-CRH (oCRH) stimulation were explored, as well as inferior petrosal
      sinus ACTH sampling before and after oCRH. Among the tumor markers examined,
      elevation of ACTH precursors was uniformly present followed by increased output
      of calcitonin, gut hormones, oncofetal and placental hormones in decreasing
      order. Since more than 90% of ectopic ACTH tumors are neuroendocrine in nature
      exhibiting APUD characteristics, their 2 markers, neuron-specific enolase and
      chromogranins are very useful. The imaging procedures for localization of the
      tumor ranged from chest X-rays to computed tomography and magnetic resonance of
      the chest and abdomen. Abdominal ultrasonography was also useful. Finally
      somatostatin receptor scintigraphy permitted demonstration of unrecognized tumors
      and/or metastases, even when the tumors were occult. The ACTH content,
      immunostaining for APUD markers and altered POMC processing were evaluated in
      ectopic tumors and/or metastases. Occult ectopic ACTH syndrome of more than 4-6
      months of symptoms without the emergence of an obvious source was reviewed. Since
      the tumors are often clinically and biochemically undistinguishable from
      pituitary-dependent Cushing's disease, inferior petrosal sinus sampling for ACTH
      after oCRH stimulation established the diagnosis in over 90% of the cases. 60% of
      the occult tumors were thoracic carcinoids (3/4 bronchial carcinoids), followed
      by small cell lung cancer and pancreatic neuroendocrine tumors. In 12% the
      primary etiology was not detected. The rare syndrome of ectopic CRH syndrome (6
      published cases) leading to excessive stimulation of the pituitary which became
      hyperplastic and secreted excessive amounts of ACTH is discussed. Finally, the 12
      published cases and 1 unreported patient with ectopic CRH-ACTH tumors were
      reviewed, the majority being metastatic small cell lung carcinomas, bronchial and
      thymic carcinoids.

PMID- 7626447
TI  - 17 alpha-Hydroxylase/17,20-lyase defects.
AB  - Congenital adrenal hyperplasia due to 17 alpha-hydroxylase/17/20-lyase deficiency
      is caused by genetic defects in the gene encoding P450c17 (CYP17). To date, 18
      different mutations in 27 individuals have been identified and all of them are
      located in the coding region of CYP17. Several mutations have been reconstructed
      in human P450c17 cDNA and expressed in COS cells to characterize the kinetic
      properties of 17 alpha-hydroxylase and 17,20-lyase activities. The molecular
      bases of cases clinically reported as 17 alpha-hydroxylase deficiency have turned
      out to result from complete or partial combined deficiencies of 17 alpha
      hydroxylase/17,20-lyase. The elucidation of the molecular bases generally
      explains the patient's clinical profiles including the sexual phenotype of the
      external genitalia. In one case initially reported as isolated 17,20-lyase
      deficiency, the molecular basis was found to be partial combined deficiency of
      both activities, somewhat discordant with the patient's clinical profile.
      However, the patient was subsequently found to have 17 alpha-hydroxylase
      deficiency, suggesting involvements of age-dependent unknown factors affecting
      P450c17 activity.

PMID- 7626449
TI  - Aromatase in bone cell: association with osteoporosis in postmenopausal women.
AB  - To clarify the possible action of adrenal androgen on bone cell, the existence,
      characteristics and regulation of aromatase in human osteoblast-like osteosarcoma
      cells (HOS) and primary cultured osteoblast-like cells from normal human bones
      (HO) were examined in this study. Significant positive correlation between bone
      mineral density (BMD) and serum dehydroepiandrosterone sulfate (DHEA-S) was found
      in 120 postmenopausal women (51-99 years old) but no correlation was seen between
      BMD and serum estradiol (E2). In subset analysis, strongly positive correlation
      of serum DHEA-S and estrone (E1) with BMD was observed in postmenopausal women
      aged less than 69 years old. Administration of DHEA to ovariectomized rat
      significantly increased BMD and decreased relative osteoid volume in femur. These
      in vivo findings strongly suggested that serum adrenal androgen may be converted
      to estrogen in peripheral organ, especially, osteoblast and be important steroids
      to maintain BMD. [3H]DHEA was converted to [3H]androstenedione and
      [3H]androstenedione to [3H]estrone in primary cultured human osteoblast.
      Osteoblast-like cells showed aromatase activity, and an apparent Km and the Vmax
      were 4.74 +/- 0.78 nM (mean +/- SD, n = 3) and 0.83 +/- 0.79 fmol/mg protein/h
      for HOS, and 4.6 +/- 2.9 nM and 279 +/- 299 fmol/mg protein/h (mean +/- SD, n =
      19) for HO, respectively. The aromatase activity was significantly increased by
      dexamethasone in a dose-dependent manner. Reverse transcription-polymerase chain
      reaction analysis revealed that dexamethasone increased the transcript of
      P450AROM gene. Osteoblast-specific promoters were also determined. Dexamethasone
      and 1 alpha,25-dihydroxyvitamin D3 synergistically enhanced aromatase activity
      and P450AROM mRNA expression. These results demonstrate that adrenal androgen,
      DHEA, is converted to E1 in osteoblast by P450AROM which is positively regulated
      by glucocorticoid and 1 alpha,25-dihydroxyvitamin D3 and important to maintain
      BMD in the 6 to 7th decade, after menopause.

PMID- 7626448
TI  - Defects in steroidogenic enzymes. Discrepancies between clinical steroid research
      and molecular biology results.
AB  - Molecular biology has clarified the understanding of steroidogenic enzyme
      genetics. Nevertheless, there are discrepancies between fundamental and clinical
      experience. (1) Why do patients with "pure" 17 alpha-hydroxylase or 17,20
      desmolase deficiency exist, when one cytochrome regulates both steps? A case of
      interest is discussed, who had "pure" 17,20-desmolase deficiency until
      adolescence, but additional 17 alpha-hydroxylase deficiency thereafter. (2) In 11
      beta-hydroxylase deficiency, it was puzzling to find 18-hydroxylated compounds,
      and, in isolated hypoaldosteronism, normal cortisol, since 11 beta- and 18
      hydroxylation were thought to be regulated together. This has now been explained
      by differences in the fasciculata and glomerulosa. The occurrence of 11 beta
      hydroxylase deficiency of 17-hydroxylated steroids only, however, remains
      enigmatic. (3) 3 beta-Hydroxysteroid dehydrogenase deficiency does not only seem
      to exist in classic (mutations of type II gene), but also in late-onset cases. In
      them, no molecular basis could be found. (4) Also, in cholesterol side-chain
      cleavage, there is an inequity: while evidently one cytochrome regulates 20- and
      22-hydroxylation, pregnenolone is formed when 20 alpha OH-cholesterol, but not
      when cholesterol, is added to adrenal tissue of deficient patients. Other factors
      (promoters, fusion proteins, adrenodoxin, cAMP-dependent expression of genes,
      and/or proteases), or hormonal replacement in patients may be responsible for
      these discrepancies.

PMID- 7626450
TI  - ARIMIDEX: a new oral, once-a-day aromatase inhibitor.
AB  - ARIMIDEX is a potent and selective aromatase inhibitor undergoing evaluation as a
      treatment for postmenopausal women with advanced breast cancer. Studies examining
      the pharmacology of ARIMIDEX were conducted in both animals and humans. In
      animals, ARIMIDEX elicits maximal aromatase suppressive activity at a dose of
      approx. 0.1 mg/kg, does not alter adrenal steroid hormone biosynthesis, and at a
      dose of 1 mg/kg, has no other pharmacologic effects other than aromatase
      inhibition. In this overview, the pharmacodynamic, pharmacokinetic, and safety
      profiles of single and multiple daily doses of ARIMIDEX are reported in humans.
      Daily doses of 1-10 mg of ARIMIDEX suppressed estradiol levels to the maximum
      degree measurable using sensitive estrogen assays. ARIMIDEX had no clinically
      significant effects on the response of cortisol and aldosterone to ACTH
      stimulation. Absorption of ARIMIDEX was rapid, with maximum plasma concentrations
      occurring within 2 h after oral administration. Plasma concentrations of ARIMIDEX
      rose with increasing doses of the drug. The elimination half-life of ARIMIDEX in
      humans ranged from 30 to 60 h. Consistent with the long plasma half-life, steady
      state plasma concentrations were 3-4-fold higher than plasma concentrations
      observed after single administration of 1, 3, 5, or 10 mg doses. Long term
      treatment of breast cancer patients with 10 mg/day has continued in 17 patients
      without an escape of estradiol suppression. Previously, these patients had
      received on average 2.6 systemic treatments for breast cancer and had significant
      metastatic disease. Three of the 17 patients continued ARIMIDEX treatment for 20
      months and beyond. Given the number of previous treatments and tumor burden at
      the start of treatment, the response to ARIMIDEX treatment is encouraging. Phase
      III studies are now underway to assess the efficacy and safety of ARIMIDEX in the
      treatment of advanced breast cancer.

PMID- 7626451
TI  - Transcriptional regulation of the human aromatase cytochrome P450 gene expression
      in human placental cells.
AB  - The human aromatase cytochrome P450 gene, CYP 19, spans more than 75 kb in the
      human genome. Recently, it is proposed that the expression of the CYP 19 gene is
      regulated in part by tissue-specific promoters through the use of mechanisms
      involving alternative splicing of a number of untranslated exons. In this study,
      we have characterized cis-acting elements involved in the transcriptional
      regulation of the gene in human placental cells, where the majority of the
      transcripts contain the 5'-untranslated sequence encoded by exon I.1. By
      transient expression analyses in human BeWo choriocarcinoma cells using the
      bacterial chloramphenicol acetyltransferase gene as a reporter gene, we localized
      an enhancer element in the region between -242 and -166 relative to the major cap
      site of the gene. Furthermore, we demonstrate that the element between -2141 and 
      2115 participates in the 12-O-tetradecanoylphorbol 13-acetate (TPA)-mediated
      enhancement of gene expression. By screening a human placental cDNA expression
      library, we have isolated a cDNA clone (lambda 1-2) encoding a peptide which
      binds specifically to the element between -2141 and -2115. Sequence analysis of
      the clone revealed that the insert of lambda 1-2 encodes a part of the amino acid
      sequence of NF-IL6 (also termed as LAP and C/EBP beta). Northern blot analysis
      reveals expression of the NF-IL6 gene in BeWo cells and human placenta. These
      results indicate that NF-IL6 is one of the nuclear factors which participate in
      TPA-mediated transcriptional enhancement of CYP 19 gene expression.

PMID- 7626452
TI  - Gene regulation of steroidogenesis.
AB  - The biosynthesis of various steroid hormones in animal tissues are catalyzed by
      six forms of cytochrome P450 and two hydroxysteroid dehydrogenases. The tissue
      specific expression of these enzymes, which are under the control of the
      pituitary gland and mainly regulated at the transcriptional level, determines the
      steroidogenesis of animal tissues. Analysis of the promoter regions of the
      steroidogenic P450 genes revealed various cis-acting elements, including cAMP
      responsive sequences (CRS), Ad4, and GC-rich sequences, which were needed for the
      tissue-specific and cAMP-dependent expression of the genes. Some of the nuclear
      protein factors binding to the cis-acting elements were isolated and
      characterized. A zinc-finger protein binding to Ad4, which was termed Ad4BP or SF
      1, seems to be of particular importance in steroidogenesis. Ad4BP was expressed
      in the cells of the steroidogenic tissues, adrenal gland and gonadal tissues, in
      the rat fetus prior to the expression of steroidogenic P450s, and remained
      expressed only in steroidogenic cells in adult animals. Close investigation of
      the temporal and spacial expression of Ad4BP in the fetal tissues suggested its
      role in the differentiation of the steroidogenic tissues and the sex
      determination of the gonadal tissues.

PMID- 7626453
TI  - A molecular model for the interaction between vorozole and other non-steroidal
      inhibitors and human cytochrome P450 19 (P450 aromatase).
AB  - In a previous study (Vanden Bossche et al., Breast Cancer Res. Treat. 30 (1994)
      43) the interaction between (+)-S-vorozole and the I-helix of cytochrome P450 19
      (P450 aromatase) has been reported. In the present study we extended the "I-helix
      model" by incorporating the C-terminus of P450 aromatase. The crystal structures
      of P450 101 (P450 cam), 102 (P450 BM-3) and 108 (P450 terp) reveal that the C
      terminus is structurally conserved and forms part of their respective substrate
      binding pocket. Furthermore, the present study is extended to the interaction
      between P450 aromatase and its natural substrate androstenedione and the non
      steroidal inhibitors (-)-R-vorozole, (-)-S-fadrozole, R-liarozole and (-)-R
      aminoglutethimide. It is found that (+)-S-vorozole, (-)-S-fadrozole and R
      liarozole bind in a comparable way to P450 aromatase and interact with both the I
      helix (Glu302 and Asp309) and C-terminus (Ser478 and His480). The weak activity
      of (-)-R-aminoglutethimide might be attributed to a lack of interaction with the
      C-terminus.

PMID- 7626454
TI  - Actions of progesterone on human sperm: a model of non-genomic effects of
      steroids.
AB  - Non-genomic actions of steroids have been extensively studied in the last few
      years. Among these actions, the non-genomic effect of progesterone (P) on human
      spermatozoa appears to be very promising, in view of the dramatic effect of this
      steroid on intracellular calcium, activation of tyrosine kinase, and induction of
      acrosome reaction. We have shown that the ability of spermatozoa to respond to P
      increases during the process of capacitation and is not counteracted by the P
      receptor antagonist RU486 nor by the GABAA antagonists bicuculline and
      picrotoxin. We have also shown that P increases tyrosine phosphorylation of a
      sperm protein of about 97 kDa, suggesting activation of tyrosine kinase(s). In
      addition, we found that P induces a perturbation of sperm membrane phospholipid
      metabolism resulting in an increase of synthesis of platelet-activating factor
      and liberation of arachidonic acid. Results of these biochemical studies indicate
      that P is able to stimulate several signal transduction pathways in human sperm.
      We have also investigated responsiveness to P in sperm of oligozoospermic
      subjects as well as of men undergoing an in vitro fertilization (IVF) program.
      Our results show that the percentage increases of intracellular calcium and
      acrosome reaction in response to P is significantly reduced in oligozoospermic
      men as well as in subjects with reduced fertilization rate. Moreover, in the
      latter subjects response to P is highly significant correlated to fertilization
      rate of oocytes. These studies indicate that a biochemical alteration of sperm in
      their capacity to respond to P might be responsible for reduced fertilizing
      ability.

PMID- 7626455
TI  - Benefits and risks of hormone replacement therapy (HRT).
AB  - In western countries more than 30% of the female population are postmenopausal.
      Approximately 30% of postmenopausal women suffer from clinical symptoms of the
      climacteric such as vasomotor symptoms, associated with hot flushes, night sweat,
      insomnia and depressive mood. Sufficient hormonal replacement therapy (HRT) will
      abolish specific menopausal symptoms in over 90% of patients, unspecific symptoms
      such as headache respond to placebo and HRT equally well. The question of cancer
      risk related to HRT will be addressed in this review. In combination with
      progestins, estrogens are obviously protective regarding ovarian and endometrial
      cancer. The association between HRT and breast cancer risk is presently unclear.
      Epidemiological data available so far do not provide compelling evidence as to a
      cause and effect relationship between HRT and breast cancer risk. There seems to
      be an overall trend towards a slightly increased risk with increasing duration of
      HRT use. Guidelines for HRT use in women with a history of endometrial and breast
      cancer are provided in this article.

PMID- 7626456
TI  - Endothelin expression in the uterus.
AB  - The endothelins (ETs) comprise a family of 21 amino acid peptides, ET-1, ET-2 and
      ET-3, first demonstrated as products of vascular endothelium. Subsequent work
      showed that they are also found in non-endothelial cells from a variety of
      tissues such as breast, parathyroid and adrenal gland. At first, the ETs were
      recognized for their pressor effects. However, ET administration in vivo
      initially caused hypotension at low concentrations by triggering the paracrine
      release of endothelial-derived vasodilators. The ETs exert powerful contractile
      actions on myometrium and other types of smooth muscle and are mitogenic, or co
      mitogenic for fibroblasts, vascular smooth muscle and other cells. Demonstration
      of extravascular ET in endometrium has revealed a powerful vasoconstrictor which
      might act on the spiral arterioles to effect a powerful and sustained contraction
      of vascular smooth muscle. ETs might also contribute to the process of
      endometrial repair. In addition, the ETs appear to play a fundamental role in the
      control of uterine function in pregnancy. Effects on myometrial contractility
      have been implicated in the mechanisms governing the onset of normal and pre-term
      labour, and the peptides are likely to be key determinants of placental blood
      flow by binding to vascular smooth muscle receptors in the placenta.

PMID- 7626457
TI  - The molecular biology of the FSH receptor.
AB  - The actions of follicle stimulating hormone (FSH) mediated through its receptor
      are necessary for the proper functioning of mammalian gonads. The FSH receptor is
      localized on granulosa cells of the ovary and Sertoli cells of the testis. The
      expression of the FSH receptor (FSHR) in Sertoli cells varies in vivo as a
      function of the stage of the cycle of the seminiferous epithelium and in culture
      as a result of the addition of exogenous hormones. The gene for the FSH receptor
      is large and has been shown to be related in structure to the genes for
      luteinizing hormone (LH) receptor and thyroid stimulating hormone (TSH) receptor.
      The promoter region of the gene for FSHR does not contain a TATA box and has
      multiple transcriptional start sites. Less than 280 bp of the promoter are
      sufficient in transient transfection assays to direct expression of the
      chloramphenicol acetyl transferase gene (CAT) in a number of different cell types
      including non-gonadal cells. However, the promoter does direct the expression of
      a marker gene only into testis and ovary of transgenic mice.

PMID- 7626458
TI  - Regulation of the genes for insulin-like growth factor (IGF) I and II and their
      receptors by steroids and gonadotropins in the ovary.
AB  - Insulin-like growth factors (IGFs) I and II are two single-chain polypeptide
      hormones that are structurally related to each other and to proinsulin. Among the
      large number of growth factors involved in ovarian physiology, IGF-I and IGF-II
      are considered to be important progression factors for ovarian follicular
      development. To explore the ovarian expression of IGF-I, IGF-II and their
      receptor genes, a solution hybridization/RNase protection assay, was used. IGF-I
      mRNA was seen in the granulosa cells, and IGF-II mRNA in the theca-interstitial
      compartment. To study the hormonal regulation of the IGF-I and IGF-II gene,
      immature (21-day-old) hypohysectomized rats were treated with FSH (10
      micrograms/day), GH (150 micrograms/day) and diethylstilbestrol (DES subcutaneous
      implant/5 days). Estrogen differentially regulated ovarian IGF-I and IGF-II gene
      expression. In concert with GH, estrogen up-regulated ovarian IGF-I mRNA, but
      significantly decreased hepatic IGF-I gene expression. Both IGF receptors (type I
      and type II) as well as the insulin receptor gene, were expressed in both ovarian
      cells. The expression of the type I IGF receptor gene (but not the type II IGF
      gene) was up-regulated by FSH and estrogen in vivo. In conclusion, these studies
      may serve to better understand the auto paracrine role of IGF, and their
      receptors in the pathophysiology of follicle recruitment, oocyte maturation and
      potentially embryo development.

PMID- 7626459
TI  - Subdermal contraceptive implants.
AB  - Subdermal contraceptive implants involve the delivery of a steroid progestin from
      polymer capsules or rods placed under the skin. The hormone diffuses out slowly
      at a stable rate, providing contraceptive effectiveness for 1-5 years. The period
      of protection depends upon the specific progestin and the type of polymer.
      Advantages of progestin implants include long term contraceptive action without
      requiring the user's or provider's attention, low dose of highly effective
      contraception without the use of estrogen, and fertility is readily reversible
      after the removal of implants. The levonorgestrel implant Norplant R system is
      the only one that has been approved for distribution. The contraceptive efficacy
      of Norplant is the highest observed amongst the most effective methods with an
      annual pregnancy rate of 0.2 during the first and second year and 1.1 on the
      fifth year. Menstrual problems are the main reason for the discontinuation of
      Norplant and 9% of women stopped using it during the first year of treatment.
      Other implants are still under development trying to simplify the method by
      reducing the number of units and to introduce other progestins that may minimize
      side effects. Norplant-2 was designed to release the same dose of progestin from
      only two covered rods. Evaluation of 1400 women enrolled, indicates that over 2
      years the cumulative pregnancy rate is below 0.5 per 100 women. There are three
      single implants under development: Nestorone, 3-Keto-desogestrel and Uniplant
      that are expected to be effective for 1-2 years. Phase II clinical trials with
      Nestorone have been completed and no pregnancies have been observed in 1570 woman
      months of use. Bleeding irregularities occurred in 20-30% of the women but there
      were only four terminations because of bleeding problems. A multricentric study
      is ongoing with a newly designed 3-keto-desogestrel implant named Implanon, which
      releases approx. 60 micrograms/day of the hormone. The objectives of this study
      are to assess contraceptive efficacy, safety and acceptability of Implanon.
      Another multricentric study is ongoing with Uniplant, which releases nomegestrol
      acetate with a duration of action for only 1 year. The objectives of the trial
      are to study the endocrine profile of Uniplant users and to evaluate the efficacy
      and acceptability of the method.

PMID- 7626460
TI  - Steroid-protein interaction in human placenta.
AB  - Human placenta produces a large variety of bioactive substances with endocrine
      and neural competence: pituitary and gonadal hormones, hypothalamic-like
      releasing or inhibiting hormones, growth factors, cytokines and neuropeptides.
      The most recent findings indicate that locally produced hormones regulate the
      secretion of other placental hormones supporting a paracrine/autocrine
      regulation. In placental endocrinology, a particular relevance is played by
      steroid hormones. In fact, a specific gonadotropin-releasing hormone (GnRH)-human
      chorionic gonadotropin (hCG) regulation of placental steroidogenesis has been
      proposed as a placental internal regulatory system acting on steroids production
      from human placenta. In addition, activin and inhibin have been proposed as
      further regulatory substances of the synthesis and secretion of steroids; the
      addition of activin A to placental culture augments GnRH, hCG and progesterone,
      and this effect can be significantly reduced by the addition of inhibins.
      Finally, a steroid-steroid interaction is suggested by the evidence that
      placental estrogen has a positive role in the regulation of progesterone
      biosynthesis. Other steroid-protein interactions have been observed in human
      placenta. In fact, recent data indicate that progesterone inhibits placental
      corticotropin-releasing factor (CRF) and estrogens act on placental conversion of
      cortisol to cortisone, activating cortisol secretion by the fetal adrenal and
      enhancing fetal adrenal function with advancing gestation.

PMID- 7626461
TI  - Role of 17 beta-estradiol and progesterone in the regulation of synthesis and
      secretion of chorionic gonadotropin by the first trimester human placenta.
AB  - The role of 17 beta-estradiol and progesterone in the regulation of synthesis of
      chorionic gonadotropin (CG) by first trimester human placenta has been studied
      using 1,4,6 androstatriene 3-17-dione to block the synthesis of 17 beta-estradiol
      or tamoxifen to block its action at receptor level and RU486 to block the action
      of progesterone at the receptor level. Results indicate that the synthesis of CG
      is negatively modulated by 17 beta-estradiol and positively modulated by
      progesterone as judged by the change in the levels of immunoreactive CG, alpha-
      and beta-CG mRNA and in vitro translation, as well as biosynthesis of alpha- and
      beta-CG and, finally, nuclear run off transcription.

PMID- 7626462
TI  - The physiology of the ovary: maturation of ovarian granulosa cells and a novel
      role for antioxidants in the corpus luteum.
AB  - During folliculogenesis the granulosa cells divide whilst in contact with each
      other, and so exhibit some of the characteristics of stem cells. In vitro we have
      shown that bovine granulosa cells from 3-7 mm follicles, like stem cells, divide
      without the need for a substratum, and produce colonies of cells. Growth factors,
      bFGF and IGF's, stimulate their division. These cells secrete and assemble a
      basal lamina, suggesting that the follicular basal lamina is produced by the
      granulosa cells. They have the morphological characteristics of follicular
      granulosa cells. Thus this system is ideal for studying the functions of immature
      granulosa cells because the cells do not spontaneously differentiate or luteinize
      into luteal cells, as occurs in culture on a substratum. On differentiation into
      luteal cells in vivo the cells express the steroidogenic enzymes for progesterone
      production and accumulate beta-carotene. During culture of bovine luteal cells we
      observed that a proportion of the steroidogenic enzyme cholesterol side-chain
      cleavage cytochrome P450 enzyme became chemically cross-linked to its electron
      donor, adrenodoxin. P450 enzymes produce oxygen free radicals and oxygen free
      radicals can cause cross-linking between proteins in close proximity. Cell
      protect against this damage by the use of antioxidant vitamins. Repleting the
      cultured luteal cells with beta-carotene reduced the amount of cross-linking. We
      conclude that the high levels of beta-carotene in corpora lutea are to protect
      against damage due to oxygen free radicals generated in the course of
      progesterone synthesis.

PMID- 7626463
TI  - Transdermal application of steroid hormones for contraception.
AB  - The concept of transdermal delivery (TD) for steroid application has nowadays
      been largely accepted for hormone replacement therapy in the menopause. It is
      only recently that the same concept has been envisaged for contraception. The
      skin can be penetrated by both estrogens and progestins, provided they are
      delivered in an appropriate solvent. About 10% of the total dose applied
      topically is actually absorbed. The transdermal delivery systems (TDS) presently
      available are either of the reservoir type (membrane-moderated system) or of the
      matrix dispersion type where the drug is dispersed into a polymer matrix.
      Estradiol (E2) is the most appropriate steroid for TD and can be combined with
      progestins to ensure a contraceptive effect. Only potent progestins should be
      used to achieve effective plasma levels with low doses in order to maintain an
      acceptable small surface of TDS. TDS changed weekly and delivering both E2 and
      levonorgestrel (L-NG) at daily dosages of 38.4 (+/- 7.5) and 28.8 (+/- 7.2)
      micrograms/10 cm2 per day respectively, showed ovulation suppression. Another
      progestin derived from norprogesterone (ST 1435) has been shown to penetrate the
      skin when suspended in acetylated lanolin or dissolved in a hydroalcoholic gel
      and to ensure ovulation suppression at a dose of 2 mg per day in a small number
      of cycles. These preliminary data demonstrate the feasibility of suppressing
      ovulation in women by transdermal absorption of steroids. Using TDS for
      contraception implies that such systems should be perfectly adhesive, well
      tolerated locally and achieve nearly 100% efficacy. These targets are very
      challenging, however, the potential advantages are so high that the concept
      deserves further development.

PMID- 7626465
TI  - Steroid regulation of parathyroid hormone-related protein expression and action
      in the rat uterus.
AB  - The gene encoding parathyroid hormone-related protein (PTHrP), an
      autocrine/paracrine inhibitor of vascular and nonvascular smooth muscle
      contractility, is regulated by hormonal steroids including estrogens (E2), 1,25
      dihydroxy vitamin D (Vit D3) and glucocorticoids. While E2 increases PTHrP gene
      expression, Vit D3 and glucocorticoids inhibit transcriptional activity of this
      gene. In the uterus of ovariectomized rats, E2-treatment increases both PTHrP
      mRNA levels and smooth muscle sensitivity to the action of PTHrP(1-34). To
      examine the action(s) of Vit D3 and glucocorticoids on these parameters, OVX rats
      were treated with E2, Vit D3 or the synthetic glucocorticoid, dexamethasone
      (Dex), alone, or with E2 following a 1 h pretreatment with Vit D3 or Dex. PTHrP
      and PTH/PTHrP receptor mRNA were measured by blot hybridization analysis of RNA
      prepared from uteri collected 2, 4 and 24 h after treatment. Uterine horns were
      used to measure the effect of the steroids on the ability of PTHrP(1-34) to
      inhibit spontaneous myometrial contraction. When E2, Vit D3 and Dex were given
      alone, only E2 altered PTHrP mRNA levels in the uterus, however, a 1 h
      pretreatment with Dex but not Vit D3 markedly diminished this effect of E2. The
      temporal decline in uterine PTH/PTHrP receptor mRNA levels measured 2 and 4 h
      after E2 treatment inversely correlated to changes in sensitivity of the tissue
      to PTHrP(1-34) measured at 24 h after E2 administration. In comparison to E2
      alone, treatment with Vit D3 and E2 augmented the uterine responsiveness to
      PTHrP(1-34) while pretreatment with Dex (1 mg/kg) and E2 decreased this response.
      These data indicate that in the uterus, Dex opposes the positive effect of E2 on
      PTHrP gene activity and differentially modulates the action of PTHrP on
      myometrial tone. Moreover, elevations in the circulating levels of cortisol at
      term may serve to decrease both the uterine expression of PTHrP and the local
      action of PTHrP on the myometrium prior to parturition, therefore promoting
      myometrial contraction associated with labor.

PMID- 7626464
TI  - Different patterns of metabolism determine the relative anabolic activity of 19
      norandrogens.
AB  - Testosterone, the principal androgen secreted by Leydig cells, exerts a wide
      range of actions including growth of the male reproductive tract (androgenic
      effects) and growth of non-reproductive tissues such as muscle, kidney, liver,
      and salivary gland (anabolic effects). As androgenic steroids were discovered
      some were found to have relatively more anabolic than androgenic activity. The
      results reviewed in this report suggest that these differences result, in part,
      from the differential metabolism of the steroids in individual tissues and the
      varied activities of the individual metabolites. In the accessory sex organs
      (e.g. the prostate) testosterone is 5 alpha-reduced to dihydrotestosterone (DHT)
      which, due to its higher affinity for androgen receptors (AR), amplifies the
      action of testosterone. In contrast, when 19-nortestosterone (NT) is 5 alpha
      reduced, its affinity for AR decreases, resulting in a decrease in its androgenic
      potency. However, their anabolic potency remains unchanged since significant 5
      alpha-reduction of the steroids does not occur in the muscle. 7 alpha-methyl-19
      nortestosterone (MENT) does not get 5 alpha-reduced due to steric hindrance from
      the 7 alpha-methyl group. Therefore, the androgenic potency of MENT is not
      amplified as happens with testosterone. These metabolic differences are
      responsible for the increased anabolic activity of NT and MENT compared to
      testosterone. Part of the biological effects of testosterone are mediated by its
      aromatization to estrogens. The fact that MENT is also aromatized to 7 alpha
      methyl estradiol, a potent estrogen, in vitro by human placental and rat ovarian
      aromatase suggests that some of the anabolic actions of MENT may be mediated by
      this estrogen.

PMID- 7626466
TI  - Sexual differentiation of brain and behavior in quail and zebra finches: studies
      with a new aromatase inhibitor, R76713.
AB  - In many species of vertebrates, major sex differences affect reproductive
      behavior and endocrinology. Most of these differences do not result from a direct
      genomic action but develop following early exposure to a sexually differentiated
      endocrine milieu. In rodents, the female reproductive phenotype mostly develops
      in the absence of early steroid influence and male differentiation is imposed by
      the early action of testosterone, acting at least in part through its central
      conversion into estrogens or aromatization. This pattern of differentiation does
      not seem to be applicable to avian species. In Japanese quail (Coturnix
      japonica), injection of estrogens into male embryos causes a permanent loss of
      the capacity to display male-type copulatory behavior when exposed to
      testosterone in adulthood. Based on this experimental result, it was proposed
      that the male reproductive phenotype is "neutral" in birds (i.e. develops in the
      absence of endocrine influence) and that endogenous estradiol secreted by the
      ovary of the female embryo is responsible for the physiological demasculinization
      of females. This model could be recently confirmed. Females indeed display a
      higher level of circulating estrogens that males during the second part of their
      embyronic life. In addition, treatment of female embryos with the potent
      aromatase inhibitor, R76713 or racemic vorozole which suppresses the endogenous
      secretion of estrogens maintains in females the capacity to display the full
      range of male copulatory behaviors. The brain mechanisms that control this
      sexually differentiated behavior have not been identified so far but recent data
      suggest that they should primarily concern a sub-population of aromatase
      immunoreactive neurons located in the lateral parts of the sexually dimorphic
      preoptic nucleus. The zebra finch (Taeniopygia guttata) exhibits a more complex,
      still partly unexplained, differentiation pattern. In this species, early
      treatment with exogenous estrogens produces a masculinization of singing behavior
      in females and a demasculinization of copulatory behavior in males.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7626467
TI  - Potential interactions between estrogen receptor and thyroid receptors relevant
      for neuroendocrine systems.
AB  - Environmental signals can profoundly affect reproductive behavior, physiology and
      responses to steroids. One consequence of nutritional or temperature stress is
      altered plasma concentrations of thyroid hormone. Recent in vivo and in vitro
      data indicate that manipulations of estrogen and thyroid hormone levels can alter
      each other's functions. One possible mechanism for interaction may be that
      thyroid and estrogen receptors bind to parts of the same hormone response
      elements of target genes and compete with each other, thus serving to integrate
      environmental signals with neuroendocrine responses.

PMID- 7626468
TI  - Regulation of hypothalamic somatostatin by glucocorticoids.
AB  - Glucocorticoids (GCs) play a key role in the physiology of the hypothalamic
      somatotroph axis, since these steroids enhance growth hormone (GH) gene
      transcription and increase GHRH receptor synthesis. However, GC excess inhibits
      normal growth in all species studied. This is mainly due to the impaired GH
      secretion observed during hypercortisolism, a situation in which GH responses to
      a number of stimuli, including GHRH, are blunted. The inhibitory effect of GCs on
      GH secretion seems to be dependent on enhanced hypothalamic SS secretion. Since
      SS release is stimulated by beta-adrenergic agonism we tested the possibility
      that GC inhibition of GH secretion would depend on increased beta-adrenoceptor
      activity in SS-producing neurons. The experimental design consisted in evaluating
      the GH response to GHRH in normal subjects after having induced hypercortisolism,
      with DEX, and blocking beta-adrenoceptors with propranolol (PRO). Moreover, to
      investigate the specificity of this mechanism, GHRH-induced GH release was tested
      after inducing hypercortisolism and enhancing alpha 2-adrenergic or muscarinic
      cholinergic tone, by giving clonidine (CLO) or pyridostigmine (PD), respectively.
      As expected, nocturnal DEX administration inhibited the GH response to GHRH. In
      this situation of hypercortisolism, both PRO and CLO, but not PD, were able to
      reverse the inhibitory effect of DEX on GHRH-elicited release. However, the
      potentiating effect of these drugs on the GHRH-induced GH secretion was only
      observed for PRO. These data confirm that GC excess inhibits GH release by
      increasing hypothalamic SS secretion, and that the mechanism is mediated by GC
      induced enhanced beta-adrenergic responsiveness. Therefore, the defective GHRH
      secretion observed in chronic hypercortisolism must be a consequence of the
      continuous blockade that SS excess exerts on GHRH-producing neurons. Our
      postulate agrees with other data in the literature showing that GCs modulate the
      secretion of some hypothalamic peptides by changing the responsiveness of the
      producing neurons from alpha 2-adrenoceptors to that of beta-adrenoceptors.

PMID- 7626469
TI  - Structure and regulation of the luteinizing hormone receptor gene.
AB  - Studies of the mechanisms controlling the expression of the rat luteinizing
      hormone receptor gene were pursued by characterization of the gene structure and
      identification of regulatory protein binding domains in the 5'-non-coding region
      of the gene and of 3' non-coding functional domains responsible for generation of
      the major mRNA forms. The coding region of the rat LHR gene contains 10 introns
      and 11 exons, of which the first 10 exons comprise the hormone binding
      extracellular domain and exon 11, the seven transmembrane/G protein coupling
      module. Several alternative spliced variants of the LHR were identified that
      conform to deletions of complete and/or partial exons. Within the 6.2 kb of the
      3'-non-coding region, two functional LHR pA domains (H1) and (H2) produce two
      sets of major mRNA transcripts, each coding for both holoreceptor and the form B
      splice variant. The H1 pA domain is unique to LHR and may represent a recombinant
      insertion domain. The functional efficiency of each pA domain is related to the
      specific pA signals, distal downstream elements, and tissue-specific factors. A
      TATA-less promoter region is present within the 173 bp 5'flanking region of the
      gene, with Initiator (Inr) elements at transcriptional start sites. Transcription
      is dependent on the binding of the Sp1 protein at two Sp1 domains that each
      contribute equally to transcript initiation. Promoter activity is regulated by at
      least three additional DNA domains, R (-1266 to -1307 bp), C-box (-42 to -73 bp)
      and M1 (-24 to -42 bp) that bind multiple trans-factors in a tissue-specific
      manner. Basal promoter activity is enhanced by a functional M1 domain in LHR
      expressing mouse Leydig tumor cells (MLTC) but not in non-expressing CHO cells. C
      box binding factors either inhibit promoter activity or block inhibition through
      overlapping but not identical DNA binding domains that carry AP-2 and NF-1
      elements. Removal of the AP-2 element within the C-box results in MLTC-specific
      transcriptional activation that may involve an MTLC M1/C-box interaction. In
      addition, competition for C-box factors by an upstream regulatory element (R)
      that is only inhibitory in CHO cells, indicates that both C-box binding factors
      compete for this upstream (R) domain in a tissue-specific manner. Competition
      between the inhibitory and neutral DNA binding factors within both upstream (R)
      and promoter domains (C-box) could provide a mechanism for the control of LH
      receptor gene expression in gonadal cells.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7626471
TI  - Involvement of a direct neural mechanism in the control of gonadal functions.
AB  - Much time has been devoted to study of the hypothalamo-hypophyseal-gonadal axis.
      However, there is now evidence of a complementary control mechanism for the
      gonads, namely a pituitary-independent, direct neural link that exists between
      the central nervous system and the gonads. We investigated whether mediobasal
      temporal lobe structures could control gonadal functions by a purely neural
      mechanism or whether they acted through the classical hypothalamo-hypophyseal
      system. Right- or left-sided deafferentiation of the temporal lobe was combined
      with right- or left-sided hemicastration in adult and prepubertal male and female
      rats. In adult females right-sided deafferentiation, regardless of the side of
      hemiovariectomy significantly reduced the extent of compensatory ovarian
      hypertrophy. Similar lesions on the left side did not interfere with the usual
      compensatory ovarian growth. This difference in compensatory hypertrophy between
      right- and left-sided lesioned rats was observed even in the face of a
      significant drop in serum LH concentrations in both groups. In pre- and
      postpubertal females temporal lobe lesion in either side was unable to alter
      compensatory hypertrophy or serum LH or progesterone concentrations. In adult
      male rats only left-sided deafferentiation combined with left orchidectomy
      resulted in decreased T production, while in prepubertal male rats, only right
      sided brain surgery plus left orchidectomy resulted in a significant decrease in
      basal testosterone secretion of the remaining testis. These findings indicate
      that mediobasal temporolimbic structures are involved in the neural control of
      gonadal functions. It appears that this lateralized mechanism is age- and sex
      dependent.

PMID- 7626472
TI  - Sexual dimorphism in the developmental regulation of brain aromatase.
AB  - Steroid sex hormones have an organizational role in gender-specific brain
      development. Aromatase (cytochrome P450AR), converting testosterone (T) to
      estradiol-17 beta (E2) is a key enzyme in brain development and the regulation of
      aromatase determines the availability of E2 effective for neural differentiation.
      Gender differences in brain development and behaviour are likely to be influenced
      by E2 acting during sensitive periods. This differentiating action has been
      demonstrated in rodent and avian species, but also probably occurs in primates
      including humans. In rodents, E2 is formed in various hypothalamic areas of the
      brain during fetal and postnatal development. The question considered here is
      whether hypothalamic aromatase activity is gender-specific during sensitive
      phases of behavioural and brain development, and when these sensitive phases
      occur. In vitro preoptic and limbic aromatase activity has been measured in two
      strains of wild mice, genetically selected for behavioural aggression based on
      attack latency, and in the BALB/c mouse. Short attack latency males show a
      different developmental pattern of aromatase activity in hypothalamus and
      amygdala to long attack latency males. Using primary brain cell cultures of the
      BALB/c mouse, sex differences in hypothalamic aromatase activity during both
      early embryonic and later perinatal development can be demonstrated, with higher
      E2 formation in males. The sex dimorphism are brain region specific, since no
      differences between male and female are detectable in cultured cortical cells.
      Immunoreactive staining with a polyclonal aromatase antibody identifies a
      neuronal rather than an astroglial localization of the enzyme. T increases fetal
      brain aromatase activity and numbers of aromatase-immunoreactive hypothalamic
      neuronal cell bodies. T appears to influence the growth of hypothalamic neurons
      containing aromatase. Differentiation of sexually dimorphic brain mechanisms may
      involve maturation of a gender-specific network of estrogen-forming neurons which
      are steroid-sensitive in early development.

PMID- 7626470
TI  - Gonadal hormone regulation of neuronal-glial interactions in the developing
      neuroendocrine hypothalamus.
AB  - Recent evidence indicates that, in addition to their well known effects on
      neurons, gonadal steroids may exert part of their neural effects through
      astroglia. In adult female rats astroglia participate in the phasic remodelling
      of synapses that takes place during the estrous cycle in the arcuate nucleus of
      the hypothalamus under the influence of estradiol. Astroglia also appear to be
      involved in the genesis of sex differences in synaptic connectivity. Gonadal
      steroids influence hypothalamic astroglia differentiation in vitro and in vivo.
      In monolayer mixed neuronal-glial cultures from fetal rat hypothalami, estradiol
      induces a progressive differentiation of astrocytes from a flattened epithelioid
      morphology to bipolar, radial and stellate shapes. This effect of estradiol on
      astroglia is dependent on the expression of specific molecules on the neuronal
      surface, such as the polysialic acid-rich form of the neural cell adhesion
      molecule. In the rat arcuate nucleus in situ, perinatal androgen influences
      astroglia gene expression and differentiation, resulting in a sex difference in
      astroglia organization by postnatal day 20. By this day, the amount of neuronal
      surface covered by astroglial processes is higher in males than in females. This
      difference in the coverage of neuronal surface by astroglia may be directly
      related to the reduced number of synaptic contacts that is established on the
      soma of male neurons compared to females.

PMID- 7626473
TI  - Long-term control of neuronal excitability by corticosteroid hormones.
AB  - Hippocampal CA1 neurons express both mineralocorticoid and glucocorticoid
      receptors. Due to the difference in affinity of the two receptor types for
      corticosterone and variations in endogenous steroid levels, occupation of the
      receptors will range between a situation of predominant mineralocorticoid
      receptor activation and conditions where both receptor types are occupied. It was
      observed that local signal transduction is regulated by activation of the
      corticosteroid receptors. Particularly, transmission mediated by biogenic amines
      appears to be sensitive to steroid control. The data indicate that cholinergic
      and serotonergic responses are small with predominant mineralocorticoid receptor
      activation, while additional glucocorticoid receptor activation results in large
      responses; the reverse has been found for noradrenalin. The steroid-dependent
      control over transmission by biogenic amines will influence local excitability
      and therefore functional processes in which the hippocampal system is involved.

PMID- 7626474
TI  - Glutamate: a major neuroendocrine excitatory signal mediating steroid effects on
      gonadotropin secretion.
AB  - The preovulatory gonadotropin surge is induced by progesterone in the cycling
      female rat or in the ovariectomized estrogen-treated female rat after adequate
      estrogen-priming activity is present. The source of progesterone under
      physiological conditions could be the ovary and/or the adrenal. Since the GnRH
      neuron does not possess estrogen and progesterone receptors, its function is
      modulated by other CNS neurotransmitters and neurosecretory products. Among
      these, excitatory amino acids (EAAs) have now been shown to play an important
      role in the regulation of pulsatile gonadotropin release, induction of puberty
      and preovulatory and steroid-induced gonadotropin surges. Glutamate, the major
      endogenous EAA exerts its action through ionotropic and metabotropic receptors.
      The ionotropic receptors consist of two major classes, the NMDA (N-methyl-D
      aspartate) and non-NMDA: kainate and AMPA (DL-alpha-amino-3-hydroxy-5-methyl-4
      isoxazole propionic acid) receptors. EAA receptors are found in hypothalamic
      areas involved with reproduction. While both NMDA and non-NMDA receptors are
      involved in the regulation of LH secretion, the NMDA receptors appear to be
      involved with the regulation of puberty and FSH secretion as well. Steroids
      increase the release rates of glutamate and aspartate in the preoptic area during
      the gonadotropin surge. Steroids may also regulate the hypothalamic AMPA
      receptors.

PMID- 7626475
TI  - Molecular genetic analysis of glucocorticoid signalling in development.
AB  - A null mutation of the glucocorticoid receptor was generated by homologous
      recombination. Mutant newborn mice showed impaired lung development, hypertrophy
      of the adrenal cortex and a strongly reduced size of the adrenal medulla.
      Phenylethanolamine N-methyltransferase (PNMT) was undetectable in the adrenals of
      the mutant mice. Serum levels of corticosterone were moderately and ACTH levels
      were strongly elevated in the mutants. A weaker but significant increase of
      corticosterone and ACTH was observed already in heterozygous animals. This points
      to a dysregulation of the HPA axis due to defective feedback regulation via the
      glucocorticoid receptor. Liver gluconeogenetic enzymes were reduced to a variable
      degree. Whereas survival of heterozygous mutants was not affected, most of the
      homozygous mutant mice died during the perinatal period.

PMID- 7626476
TI  - Metabolism of steroids in pure cultures of neurons and glial cells: role of
      intracellular signalling.
AB  - In the brain, the 5 alpha-reductase converting testosterone (T) is present both
      in neurons and in glial cells, even if it prevails in neurons; the 3 alpha
      hydroxysteroid-dehydrogenase (3 alpha-HSD), the enzyme converting
      dihydrotestosterone (DHT) into 3 alpha-diol, is particularly concentrated in type
      1 astrocytes. In glial cells, since the 5 alpha-reductase is activated by a cAMP
      analogue, PKA seems to be involved in the control of this enzyme, postulating
      that nervous inputs utilizing cAMP as the second messenger might modify the
      activity of this enzyme in glial cells. Moreover, the results indicate that, in
      type 1 astrocytes, both the 5 alpha-reductase and the 3 alpha-HSD are stimulated
      by the co-culture with neurons and by the addition of neuron-conditioned medium,
      suggesting that secretory products released by neurons might intervene in the
      control of glial cell function.

PMID- 7626477
TI  - Hypothalamic excitatory amino acid system during sexual maturation in female
      rats.
AB  - The present results indicate that during sexual maturation the APOA-MBH from rats
      of 30 days of age released significantly higher quantities of GnRH than the
      tissue from 16-day-old rats (P < 0.01). The addition of NMDA, an agonist of the
      excitatory amino acids system (EAAs), to the medium after 30 min of incubation
      significantly increased (P < 0.01) the GnRH release in normal rats of both ages
      and this increase was significantly (P < 0.01) higher in 30-day-old rats (to
      661%) than in rats of 16 days of age (to 273%). The administration of estrogen
      progesterone (EP) to rats of 16 days of age did not modify the GnRH release
      response to NMDA. On the contrary, at 30 days of age EP administration
      significantly potentiated the GnRH release response to NMDA since while in the
      control group NMDA increased the GnRH release to 630%, in the EP-pretreated group
      this was to around 4700% (P < 0.01). EP pretreatment of prepubertal rats
      decreases the hypothalamic release of aspartate and glutamate, the excitatory
      amino acids involved in NMDA neurotransmission and glycine but increases EAAs
      release in peripubertal rats. On the basis of these results it is proposed that
      the increase in EAAs release by the hypothalamus is directly connected with the
      onset of puberty and that the maturation of the positive feedback effect of
      ovarian hormones on gonadotropin secretion is related to the maturation of the
      capacity of EP to increase hypothalamic EAAs. Before this maturational event EP
      inhibits EAAs release as well as gonadotropin release (prepubertal rats). NMDA
      receptor stimulation leads to a positive mechanism which increases the release of
      Asp and Glu from APOA-MBH both in prepubertal and peripubertal rats, but EP
      potentiates this mechanism only in peripubertal rats. This could be an additional
      neuroendocrine mechanism involved in the increase of gonadotropin during sexual
      maturation which induces the onset of puberty and the preovulatory discharge of
      these pituitary hormones.

PMID- 7626478
TI  - Effects of steroids on the brain opioid system.
AB  - The experiments reported here add further evidence in support of the view that
      sex steroids may influence the binding characteristics of brain opioid receptors.
      In particular, it has been shown that: (a) the number of mu-opioid receptors
      varies in the hypothalamus of regularly cycling female rats according to the
      different phases of the estrous cycle, which are characterized by fluctuations of
      circulating levels of sex steroids; (b) the number of mu-opioid receptors
      decreases in the hypothalamus and in the corpus striatum when ovariectomized rats
      are submitted to treatments with estradiol and progesterone able to induce a
      "positive" feedback effect on LH release. A treatment with estrogen alone able to
      induce a "negative" feedback effect on LH release brings about an increase of the
      number of mu-opioid receptors in the thalamus and in the hippocampus; (c) in
      addition to the mu-receptors, receptors of the delta type may also be involved in
      the control of gonadotropin secretion; recent results here presented indicate
      that a line of immortalized hypothalamic cells (GT1 cells), which synthesize and
      secrete LHRH, present delta opioid receptors on their membranes; these are
      apparently involved in the control of LHRH release from these cells.

PMID- 7626479
TI  - Catecholamines in steroid-dependent brain development.
AB  - Sex-specific peculiarities of catecholamine (CA) content and turnover in
      neuroendocrine brain areas and their modification with neonatal steroids or
      prenatal stress (PS) in Wistar rats were studied. No changes in noradrenaline
      (NA) content and turnover rate were found in the preoptic area (POA), meanwhile
      dopamine (DA) turnover rates in the POA and mediobasal hypothalamus (MBH) were
      increased in neonatally androgenized 10-day-old females. Treatment of female
      neonates with various catecholestrogens increased hypothalamic NA content by 30
      95% but only 4-hydroxyestradiol-17 beta induced anovulation. 6-Hydroxydopamine
      had no significant impact on hypothalamic CA content in neonates and did not
      prevent testosterone-induced persistent estrous. Maternal stress (restriction for
      1 h a day, 15-21st days of pregnancy) resulted in a decrease of hypothalamic NA
      and blood plasma corticosterone response to acute stress in adult male offspring.
      Sex differences in CA content in the POA and MBH disappeared in 10-day-old
      prenatally stressed rats. CONCLUSIONS: (1) sexual brain differentiation needs co
      operative actions of sex steroids and CA to be completed; and (2) early changes
      in CA content and turnover induced by PS or neonatal steroid exposure
      predetermine long-term alterations of the stress responsiveness, reproductive
      behaviour and neuroendocrine control of ovulation.

PMID- 7626480
TI  - Biosynthesis and assay of neurosteroids in rats and mice: functional correlates.
AB  - Pregnenolone (PREG), synthesized de novo in rodent brain, is the precursor of
      PREG sulfate (S) and progesterone (PROG). PROG is further converted to 5 alpha
      pregnane 3, 20-dione (DH PROG) and to 3 alpha-hydroxy-5 alpha-pregnan-20-one (TH
      PROG). PROG, DH PROG and TH PROG have been measured in the brain of male and
      female rats. Neither PROG nor DH PROG disappeared from brain, contrary to plasma,
      after combined adrenalectomy (ADX) and gonadectomy (CX). Trilostane decreased
      PROG and increased PREG in the brain of CX+ADX rats and mice, in accordance with
      a precursor to product relationship. As previously described in CX male mice, the
      neurosteroid DHEA and its analog 3 beta-methyl-androst-5-en-17-one (CH3-DHEA)
      inhibited the aggressive behavior of female mice towards lactating female
      intruders. The decrease of biting attacks by DHEA was definitely more prominent
      in females neonatally imprinted with testosterone. The degree of inhibition of
      aggressive behavior was related to the decrease of PREG S concentrations in
      brain. The memory-enhancing effects of DHEA S and PREG S in male mice have been
      previously documented. Infusion of PREG S (12 fmol) into the nucleus basalis
      magnocellularis (NBM) of the rat after the acquisition trial enhanced memory
      performance in a two-trial recognition task (TTRT). Conversely, TH PROG (6 fmol),
      which potentiates GABAergic neurotransmission, disrupted performance when
      injected before the acquisition trial. Accordingly, we have found a positive
      correlation between the performances of 2-year-old rats in the TTRT and the
      concentrations of PREG S in the hippocampus, namely animals which performed best
      had the highest steroid levels.

PMID- 7626481
TI  - Oestrogen receptor independent expression of progestin receptors in human
      meningioma--a review.
AB  - Human meningiomas are rich in progestin receptors (PR), which are expressed in
      this tissue in an oestrogen independent fashion. In the search for an explanation
      of this observation, the existence of a protein in human meningioma cytosol which
      is capable of binding to a synthetic oestrogen responsive element (ERE) has been
      demonstrated. Using reverse transcriptase, PCR mRNA encoding for the wild-type
      oestrogen receptor (ER) was found. In addition, several splice variants of ER
      mRNA have been identified in human meningioma tissue, including variants lacking
      exons 4, 5 and 7. We found the ER delta 4 protein to have no transcriptional
      activity and the ER delta 7 protein reportedly is dominant negative. These
      mutants therefore probably are not responsible for the autonomous PR synthesis in
      human meningioma. The ER delta 5 protein, by contrast, has been reported to have
      oestrogen independent transcriptional activity and it is tempting to speculate
      that this protein is similar or identical to the ERE binding protein we have
      found in human meningioma. The role of wild type ER mRNA is presently unclear.
      Activation of other signal transduction pathways in meningioma does not lead to
      an increased PR concentration. The promoter area of the meningioma PR gene should
      be investigated for the possible sensitivity to other transcription factors.

PMID- 7626482
TI  - Oxidative and reductive pathways of estrogens in hormone responsive and non
      responsive human breast cancer cells in vitro.
AB  - In order to measure the formation and degradation rates of estradiol by human
      breast cancer cells, after assessing the biochemical basis of hormone
      responsiveness and growth response to estrogens, we considered both responsive,
      estrogen receptor (ER) positive, and non-responsive, ER-negative, breast cancer
      cell lines, i.e. MCF7, ZR75-1 and MDA-MB231. To this end, we employed a novel
      "intact cell" approach which allows us, after 24 h incubation, to analyze several
      enzyme activities in sequence, concurrently with the monitoring of labeled
      precursor degradation. Our investigations led to the following evidence: (a) the
      reductive activity of the 17 beta-hydroxysteroid oxoreductase (17 beta-HSOR)
      appears to be higher than the oxidative only in responsive, ER-rich MCF7 and ZR75
      1 cells, as also previously observed by others; (b) this activity is, on the
      contrary, much lower in MDA-MB231 cells and other unresponsive, ER-poor breast
      cancer cell lines; (c) conversely, the oxidative activity shows an opposite
      pattern, being limited in MCF7 and ZR75-1 cells and much higher in MDA-MB231
      cells. Overall, a 17 beta-HSOR reductive pathway prevails in both MCF7 and ZR75-1
      cells, whilst the oxidative pathway is prevalent in MDA-MB231 cells, leading to a
      large formation of estrone that is no further metabolized, at least in the
      experimental conditions used. Our results may provide a likely explanation of
      previous data on the different estrogen content of breast tumor tissues.

PMID- 7626483
TI  - The molecular biology of androgenic 17 beta-hydroxysteroid dehydrogenases.
AB  - The enzyme 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) catalyzes the 17
      beta-oxidation/reduction of C18- and C19-steroids in a variety of tissues. Three
      human genes encoding isozymes of 17 beta-HSD, designated 17 beta-HSD types 1, 2
      and 3 have been cloned. 17 beta-HSD type 1 (also referred to as estradiol 17 beta
      dehydrogenase) catalyzes the conversion of estrone to estradiol, primarily in the
      ovary and placenta. The 17 beta-HSD type 2 is expressed to high levels in the
      liver, secretory endometrium and placenta. The type 2 isozyme catalyzes the
      oxidation of androgens and estrogens equally efficiently. Also, the enzyme
      possesses 20 alpha-HSD activity demonstrated by its ability to convert 20 alpha
      dihydroprogesterone to progesterone. Testicular 17 beta-HSD type 3 catalyzes the
      conversion of androstenedione to testosterone, dehydroepiandrosterone to 5
      androstenediol and estrone to estradiol. The 17 beta-HSD3 gene is mutated in male
      pseudohermaphrodites with the genetic disease 17 beta-HSD deficiency.

PMID- 7626484
TI  - Basic fibroblast growth factor and ovarian cancer.
AB  - The factor(s) which regulate the rapid growth of ovarian epithelial carcinoma, as
      well as other types of malignant tumors, are still largely unknown. Recently,
      experimental evidence indicated that neoplastic cells are able to synthesize
      peptide growth factor and their receptors. This autocrine secretion could be one
      of the mechanisms to sustain their abnormal proliferation. In this study, we
      evaluated the possible role of basic fibroblast growth factor (bFGF) that is a
      likely candidate because it has both angiogenic and mitogenic activity and has
      been found in a variety of other neoplasms. As assessed by both bioassay and
      radioimmunoassay, a bFGF-like protein was present in seven ovarian epithelial
      neoplasms and in primary culture of dispersed ovarian cancer cells. Levels of
      this protein as well as its bioactivity varied in the different tumors examined.
      Reverse transcription-polymerase chain reaction indicated that the genes for bFGF
      and its receptor are expressed in all the samples studied. These data suggest
      that bFGF might be one of the growth factor regulating ovarian cancer cell
      proliferation through an autocrine mechanism. We are currently investigating
      whether the expression of this growth factor varies as a function of the
      histologic grade of the tumors.

PMID- 7626485
TI  - Effects of 5 alpha-reductase inhibitors on intraprostatic androgens in the rat.
AB  - FCE 27837 is a novel inhibitor of 5 alpha-reductase, the enzyme responsible for
      the conversion of testosterone (T) to 5 alpha-dihydrotestosterone (DHT). The
      compound caused inhibition of human and rat prostatic enzymes, with IC50 values
      of 51 and 60 nM, respectively. The in vivo effect of FCE 27837 on 5 alpha
      reductase was evaluated in adult male rats, treated orally at 10 mg/kg/day for 10
      days. The compound caused 33 and 42% reductions in ventral prostate and seminal
      vesicle weights, respectively. The prostatic content of DHT, measured 6 h after
      the 10th dose of FCE 27837, was reduced by 75%, whereas T content increased by
      442%. Similar effects were observed with 10 mg/kg/day of finasteride, whereas
      epristeride, tested at the same oral dose, was found to be the least effective
      compound, decreasing prostate weight by 22% and DHT content by 46%. Castration
      caused > 90% reductions in prostatic weight and prostatic DHT.

PMID- 7626486
TI  - Antiestrogens: mechanisms and actions in target cells.
AB  - Antiestrogens, acting via the estrogen receptor (ER) evoke conformational changes
      in the ER and inhibit the effects of estrogens as well as exerting anti-growth
      factor activities. Although the binding of estrogens and antiestrogens is
      mutually competitive, studies with ER mutants indicate that some of the contact
      sites of estrogens and antiestrogens are likely different. Some mutations in the
      hormone-binding domain of the ER and deletions of C-terminal regions result in
      ligand discrimination mutants, i.e. receptors that are differentially altered in
      their ability to bind and/or mediate the actions of estrogens vs antiestrogens.
      Studies in a variety of cell lines and with different promoters indicate marked
      cell context- and promoter-dependence in the actions of antiestrogens and variant
      ERs. In several cell systems, estrogens and protein kinase activators such as
      cAMP synergize to enhance the transcriptional activity of the ER in a promoter
      specific manner. In addition, cAMP changes the agonist/antagonist balance of
      tamoxifen-like antiestrogens, increasing their agonistic activity and reducing
      their efficacy in reversing estrogen actions. Estrogens, and antiestrogens to a
      lesser extent, as well as protein kinase activators and growth factors increase
      phosphorylation of the ER and/or proteins involved in the ER-specific response
      pathway. These changes in phosphorylation alter the biological effectiveness of
      the ER. Multiple interactions among different cellular signal transduction
      systems are involved in the regulation of cell proliferation and gene expression
      by estrogens and antiestrogens.

PMID- 7626487
TI  - Growth of the androgen-dependent tumor of the prostate: role of androgens and of
      locally expressed growth modulatory factors.
AB  - The crucial role played by androgens in the growth of prostatic carcinoma is now
      well established. However, the mechanisms of this proliferative action are still
      poorly understood. Experiments have been performed to clarify: (1) the metabolism
      of androgens in prostatic tumor cells; and (2) the role played by locally
      produced growth factors in the autocrine regulation of prostatic tumor cell
      proliferation and the possible regulation exerted by testosterone (T) on the
      activity of these factors. These studies have been performed by utilizing the
      human androgen-responsive prostatic cancer LNCaP cell line. (1) By incubating
      LNCaP cells with different 14C-labeled androgenic precursors, it has been shown
      that all the major key enzymes involved in the metabolism of androgens (5 alpha
      reductase, 17 beta-hydroxysteroid-oxidoreductase, 3 alpha- and 3 beta
      hydroxysteroid-oxidoreductases) are present and active in these cells. In
      particular, the 5 alpha-reductase, which converts T and delta 4 to DHT and 5
      alpha-A respectively, seems to be more active when delta 4 is the substrate,
      suggesting a preference for this precursor. (2) The hypothesis that LNCaP cells
      might produce LHRH (or a LHRH-like peptide) has been verified by RT-PCR,
      performed in the presence of a pair of specific oligonucleotide primers. A cDNA
      band of the expected size (228 bp), which specifically hybridized with a 32P
      labeled LHRH oligonucleotide probe, has been obtained in LNCaP cells. To clarify
      the possible role played by this factor in the regulation of tumor growth, LNCaP
      cells, cultured in steroid-free conditions, have been treated with a LHRH
      antagonist; the treatment resulted in a significant increase of cell
      proliferation. Taken together, these data indicate that a LHRH (or LHRH-like)
      growth modulatory system is expressed in LNCaP cells and plays an inhibitory role
      in the regulation of tumor cell proliferation. This system seems to be regulated
      in a negative way by steroids. Growth factors endowed with stimulatory activity,
      such as EGF and TGF alpha, have also been shown to be produced by LNCaP cells.
      The present studies show that the immunoprecipitation of the EGF receptor with a
      specific monoclonal antibody (Ab225) reveals a protein band of the expected size
      (170 kDa) which is phosphorylated even in basal conditions. Moreover, the
      treatment of LNCaP cells, cultured in serum-free conditions, either with a
      monoclonal antibody against the EGF receptor, or with immunoneutralizing
      antibodies against EGF and TGF alpha, results in a significant decrease of cell
      proliferation.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7626488
TI  - Estrone sulfate-sulfatase and 17 beta-hydroxysteroid dehydrogenase activities: a
      hypothesis for their role in the evolution of human breast cancer from hormone
      dependence to hormone-independence.
AB  - The evaluation of estrogens (estrone, estradiol, and their sulfates) in the
      breast tissue of post-menopausal patients with breast cancer indicates high
      levels, particularly of estrone sulfate (E1S) which is 15-25 times higher than in
      the plasma. Breast cancer tissue contains the enzymes necessary for local
      synthesis of estradiol and it was demonstrated that, despite the presence of the
      sulfatase and its messenger in hormone-dependent and hormone-independent breast
      cancer cells, this enzyme operates particularly in hormone-dependent cells.
      Different progestins: Nomegestrol acetate, Promegestone, progesterone, as well as
      Danazol, can block the conversion of E1S to E2 very strongly in hormone-dependent
      breast cancer cells. The last step in the formation of estradiol is the
      conversion of E1 to this estrogen by the action of 17 beta-hydroxysteroid
      dehydrogenase. This activity is preferentially in the reductive direction
      (formation of E2) in hormone-dependent cells, but oxidative (E2-->E1) in hormone
      independent cells. Using intact hormone-dependent cells it was observed that
      Nomegestrol acetate can block the conversion of E1 to E2. It is concluded,
      firstly, that in addition to ER mutants other factors are involved in the
      transformation of hormone-dependent breast cancer to hormone-independent, this
      concerns the enzymatic activity in the formation of E2; it is suggested that
      stimulatory or repressive factor(s) involved in the enzyme activity are
      implicated as the cancer evolves to hormone-independence; secondly, different
      drugs can block the conversion of E1S to E2. Clinical trials of these "anti
      enzyme" substances in breast cancer patients could be the next step to
      investigate new therapeutic possibilities for this disease.

PMID- 7626489
TI  - Distribution of 3 alpha-hydroxysteroid dehydrogenase in rat brain and molecular
      cloning of multiple cDNAs encoding structurally related proteins in humans.
AB  - 3 alpha-Hydroxysteroid dehydrogenase in the brain is responsible for production
      of neuroactive tetrahydrosteroids that interact with the major inhibitory gamma
      aminobutyric acid receptor complexes. Distribution of 3 alpha-hydroxysteroid
      dehydrogenase in different regions of the brain in rats was evaluated by activity
      assay and by Western immunoblotting using a monoclonal antibody against liver 3
      alpha-hydroxysteroid dehydrogenase as the probe. The olfactory bulb was found to
      contain the highest level of 3 alpha-hydroxysteroid dehydrogenase activity, while
      moderate levels of the enzyme activity were found in other regions such as
      cerebellum, cerebral cortex, hypothalamus and pituitary. Some activity was found
      in the rest of the brain such as amygdala, brain stem, caudate putamen, cingulate
      cortex, hippocampus, midbrain, and thalamus. The protein levels of 3 alpha
      hydroxysteroid dehydrogenase in different regions of the brain as detected by
      Western immunoblotting are comparable to those of the enzyme activity. We used
      the rat cDNA as the probe to screen a human liver lambda gt11 cDNA library. A
      total of four different cDNAs were identified and sequenced. One of the cDNAs is
      identical to that of the human chlordecone reductase cDNA except that our clone
      contains a much longer 5'-coding sequence than previously reported. The other
      three cDNAs display high degrees of sequence homology to those of both rat 3
      alpha-hydroxysteroid dehydrogenase and human chlordecone reductase. We are
      currently investigating the functional relationship between the enzymes encoded
      by these human cDNAs and 3 alpha-hydroxysteroid dehydrogenase.

PMID- 7626490
TI  - The role of cytokines and sulphatase inhibitors in regulating oestrogen synthesis
      in breast tumours.
AB  - Synthesis of oestrogens within breast tissues makes an important contribution to
      the high concentrations of oestradiol which are found in breast tumours. The
      activities of the enzymes involved in oestrogen synthesis, i.e. the aromatase,
      oestradiol dehydrogenase (E2DH) and oestrone sulphatase (E1-STS), can be
      stimulated by several growth factors and cytokines. As it is possible that some
      of these factors may be derived from cells of the immune system (macrophages and
      lymphocytes), the effects of basic fibroblast growth factor (bFGF) and
      interleukin-2 (IL-2), which are produced by these cells, on E2DH activity was
      examined in MCF-7 cells. Treatment of these cells with bFGF resulted in a dose
      dependent increase in E2DH reductive activity whereas IL-2 was inactive at the
      concentration tested. To obtain further evidence that factors produced by
      macrophages and lymphocytes can modulate the activities of enzymes involved in
      oestrogen synthesis, conditioned medium was collected from these cells and found
      to stimulate both E1-STS and E2DH activities. In addition to understanding the
      control of oestrogen synthesis in breast tumours an inhibitor to block the
      synthesis of oestrone via the oestrone sulphatase pathway was developed. Oestrone
      3-O-sulphamate (EMATE) is a potent, irreversible, inhibitor of E1-STS. A single
      dose of EMATE (10 mg/kg) inhibited tissue E1-STS activity in rats by more than
      95% for up to 7 days, indicating that this compound may have considerable
      therapeutic potential for the treatment of breast cancer. Evidence is also
      reviewed that another steroid sulphatase, dehydroepiandrosterone sulphate
      sulphatase, may have a crucial role in regulating cytokine production and that
      this may indirectly control tumour oestrogen synthesis.

PMID- 7626491
TI  - Steroid hormone receptor status defines the MMTV promoter chromatin structure in
      vivo.
AB  - The ability to respond to small signalling molecules such as steroid hormones is
      important for many physiological processes. Steroid hormones act through a group
      of high affinity receptors that regulate transcription by binding to hormone
      response elements (HREs) located within the promoters of target genes, which
      themselves are organized with nuclear proteins to form chromatin. To dissect the
      mechanisms(s) of steroid hormone action we have used the steroid inducible mouse
      mammary tumor virus (MMTV) promoter as a model system. The MMTV promoter is
      assembled into a phased array of nucleosomes that are specifically positioned in
      rodent cells. Induction of transcription by glucocorticoids is accompanied by the
      appearance of a hypersensitive region in the proximal promoter which allows the
      hormone dependent assembly of a preinitiation complex including transcription
      factors such as nuclear factor 1 (NF1) and the octamer transcription factor
      (OTF). Surprisingly, when introduced by transient transfection, the progesterone
      receptor (PR) is unable to activate this promoter in vivo, a finding that may
      result from its inability to alter MMTV promoter chromatin. In an attempt to
      investigate the failure of the PR to activate the promoter, we have stably
      introduced the MMTV promoter into human T47D breast cancer cells that express
      high levels of the PR. In contrast to what has been observed previously in rodent
      cells, the MMTV templates resident in human breast cancer cells adopt a novel and
      constitutively open chromatin structure. The constitutively open chromatin
      structure is accompanied by the hormone independent loading of transcription
      factors including the PR and NF1. In T47D cells that stably express the
      glucocorticoid receptor, the MMTV promoter responds to glucocorticoids, but not
      progestins, and displays glucocorticoid induced restriction enzyme
      hypersensitivity and transcription factor loading. These findings suggest that
      the organization of the MMTV chromatin structure is dependent upon the cell type
      and receptor status of the recipient cell into which the MMTV promoter is stably
      introduced.

PMID- 7626492
TI  - Differentiation induction of human leukemia cells (HL60) by a combination of 1,25
      dihydroxyvitamin D3 and retinoic acid (all trans or 9-cis).
AB  - 1,25(OH)2D3 and two stereoisomers of retinoic acid, all trans and 9-cis retinoic
      acid, are regulators of cell proliferation and differentiation. The aim of this
      study was to evaluate the effects of a combination of 1,25(OH)2D3 and retinoic
      acid (all trans or 9-cis) on proliferation and cell differentiation of the human
      promyelocytic leukemia cell line HL60, and to test the reversibility of the
      induced differentiation. Cell proliferation was inhibited as expected by
      1,25(OH)2D3 and all trans retinoic acid alone (IC50 of cell survival was 4 x 10(
      7) M, 9 x 10(-6) M and 9 x 10(-7) M for 1,25(OH)2D3, all trans and 9-cis retinoic
      acid, respectively). Combination of 1,25(OH)2D3 and either form of retinoic acid
      resulted in a partially additive decrease in cell proliferation. 1,25(OH)2D3
      induced a monocytic differentiation (100% CD14+ cells with 10(-7) M 1,25(OH)2D3),
      while retinoic acid led to a predominantly granulocytic differentiation (36 and
      42% CD67+ cells with 10(-6) M all trans and 9-cis retinoic acid, respectively).
      Additive effects on differentiation were observed upon combination of
      subtherapeutical doses of the drugs, achieving a mainly monocytic population,
      demonstrating the dominant role of 1,25(OH)2D3 in determining the direction of
      differentiation. The effects on proliferation and differentiation of the solitary
      drugs were reversible, while the proliferation arrest and differentiation induced
      by the combination persisted and even progressed after withdrawal of the drugs.
      We conclude that 1,25(OH)2D3 and retinoic acid (all trans or 9-cis) exert
      additive effects on inhibition of proliferation and induction of cell
      differentiation of HL60 cells, leading to a persistent differentiation, even
      after drug withdrawal.

PMID- 7626493
TI  - Androgen receptor mutations.
AB  - Male sexual differentiation and development proceed under direct control of
      androgens. Androgen action is mediated by the intracellular androgen receptor,
      which belongs to the superfamily of ligand-dependent transcription factors. At
      least three pathological situations are associated with abnormal androgen
      receptor structure and function: androgen insensitivity syndrome (AIS), spinal
      and bulbar muscular atrophy (SBMA) and prostate cancer. In the X-linked androgen
      insensitivity syndrome, defects in the androgen receptor gene have prevented the
      normal development of both internal and external male structures in 46,XY
      individuals. Complete or gross deletions of the androgen receptor gene have not
      been found frequently in persons with complete androgen insensitivity syndrome.
      Point mutations at several different sites in exons 2-8 encoding the DNA- and
      androgen-binding domain, have been reported for partial and complete forms of
      androgen insensitivity. A relatively high number of mutations were reported in
      two different clusters in exon 5 and in exon 7. The number of mutations in exon 1
      is extremely low and no mutations have been reported in the hinge region, located
      between the DNA-binding domain and the ligand-binding domain and which is encoded
      by the first half of exon 4. Androgen receptor gene mutations in prostate cancer
      are very rare and are reported only in exons 4-8. The X-linked spinal and bulbar
      muscle atrophy (SBMA; Kennedy's disease) is associated with an expanded length (>
      40 residues) of one of the polyglutamine stretches in the N-terminal domain of
      the androgen receptor.

PMID- 7626494
TI  - Progesterone receptor and the mechanism of action of progesterone antagonists.
AB  - Currently available progesterone antagonists have been suggested to fall into two
      categories based on differences in how they interact with and inactivate the
      progesterone receptor (PR). The anti-progestin ZK98299 (Type I) impairs PR
      association with DNA, while Type II compounds (RU486, ZK112993, ZK98734) promote
      PR binding to DNA. Type II agents, therefore, appear to inhibit receptor activity
      at a step downstream of DNA binding, presumably failing to induce conformational
      changes in PR structure requird for enhancement of transcription. This paper
      discusses both published and unpublished data supporting the concept of two types
      of progestin antagonists. Using PR-mediated induction of reporter genes in breast
      cancer cells as an assay for biological response, both types of anti-progestins,
      after correction for difference in steroid binding affinity, inhibit progestin
      induction substoichiometrically. However, Type II anti-progestins are more
      potent, inhibiting at lower ratios of antagonist to agonist than ZK98299. This
      suggests that in addition to behaving by classical competitive mechanisms these
      compounds (in particular Type II) may exhibit additional activity as
      transrepressors of PR in the same cell bound to hormone agonist. Transrepression
      may occur by the combined mechanisms of heterodimerization and competition for
      binding to DNA. In support of this, mixed ligand dimers form readily in solution
      between a PR subunit bound to agonist and another bound to either type of anti
      progestin, whereas these mixed ligand dimers bind poorly, if at all, to specific
      progesterone response elements (PREs) in vitro. Additionally, when added as a
      single ligand, Type II agents increase PR dimerization in solution and PR
      affinity for PREs as compared with single ligand dimers formed by progestin
      agonist. This contrasts with ZK98299, when given as a single ligand, which
      reduces PR affinity for PREs without disrupting solution dimerization. Thus the
      higher affinity of PR for PREs may account for the greater biological potency of
      Type II compounds as compared with ZK98299. As a further distinction between
      types of antiprogestins, ZK98299 minimally stimulates phosphorylation of PR
      whereas RU486 increases site-specific phosphorylation of PR in a manner
      indistinguishable from that of hormone agonist. Additionally, ZK98299 is not
      susceptible in vivo to functional switching to a partial agonist by cross talk
      with cAMP signal transduction pathways, as occurs with Type II compounds. Thus,
      ZK98299 under certain conditions may be a more pure antagonist than Type II
      compounds.

PMID- 7626495
TI  - The cellular retinoic acid binding proteins.
AB  - The two cellular retinoic acid binding proteins, CRABP I and CRABP II, belong to
      a family of small cytosolic lipid binding proteins and are highly conserved
      during evolution. Both proteins are expressed during embryogenesis, particularly
      in the developing nervous system, craniofacial region and limb bud. CRABP I is
      also expressed in several adult tissues, however, in contrast, CRABP II
      expression appears to be limited to the skin. It is likely that these proteins
      serve as regulators in the transport and metabolism of retinoic acid in the
      developing embryo and throughout adult life. It has been proposed that CRABP I
      sequesters retinoic acid in the cytoplasm and prevents nuclear uptake of retinoic
      acid. A role in catabolism of retinoic acid has also been proposed. Recent gene
      targeting experiments have shown that neither of the two CRABPs are essential for
      normal embryonic development or adult life. Examination of CRABP I expression at
      subcellular resolution reveals a differential cytoplasmic and/or nuclear
      localization of the protein. A regulated nuclear uptake of CRABP I implies a role
      for this protein in the intracellular transport of retinoic acid. A protein
      mediated mechanism which controls the nuclear uptake of retinoic acid may play an
      important role in the transactivation of the nuclear retinoic acid receptors.

PMID- 7626496
TI  - Fatty acid activation of peroxisome proliferator-activated receptor (PPAR).
AB  - Peroxisome proliferators such as clofibric acid, nafenopin, and WY-14,643 have
      been shown to activate peroxisome proliferator-activated receptor (PPAR), a
      member of the steroid nuclear receptor superfamily. We have cloned the cDNA from
      rat that is homologous to that from mouse, which encodes a 97% similar protein.
      To search for physiologically occurring activators, we established a
      transcriptional transactivation assay by stably expressing in CHO cells a chimera
      of rat PPAR and the human glucocorticoid receptor that activates expression of
      the placental alkaline phosphatase reporter gene under the control of the mouse
      mammary tumor virus promoter. 150 microM concentrations of arachidonic or
      linoleic acid but not of dehydroepiandrosterone, cholesterol, or 25-hydroxy
      cholesterol, activated the receptor chimera. In addition, saturated fatty acids
      induced the reporter gene. Shortening the chain length to n = 6 or introduction
      of an omega-terminal carboxylic group abolished the activation potential of the
      fatty acid. To test whether a common PPAR binding metabolite might be formed from
      free fatty acids we tested the effects of differentially beta-oxidizable fatty
      acids and inhibitors of fatty acid metabolism. The peroxisomal proliferation
      inducing, non-beta-oxidizable, tetradecylthioacetic acid activated PPAR to the
      same extent as the strong peroxisomal proliferator WY-14,643, whereas the
      homologous beta-oxidizable tetradecylthiopropionic acid was only as potent as a
      non-substituted fatty acid. Cyclooxygenase inhibitors, radical scavengers or
      cytochrome P450 inhibitors did not affect activation of PPAR. In conclusion, beta
      oxidation is apparently not required for the formation of the PPAR-activating
      molecule and this moiety might be a fatty acid, its ester with CoA, or a further
      derivative of the activated fatty acid prior to beta-oxidation of the acyl-CoA
      ester.

PMID- 7626497
TI  - Regulation of ferredoxin gene in steroidogenic and nonsteroidogenic cells.
AB  - Ferredoxin is an electron transport intermediate for all the mitochondrial
      cytochromes P450. It is especially abundant in steroidogenic organs where it
      functions in steroid biosynthesis. The regulation of ferredoxin gene expression
      was studied in both steroidogenic and nonsteroidogenic cell lines. In
      steroidogenic cell line Y1, the expression of ferredoxin was stimulated by cAMP
      and repressed slightly by angiotensin II and phorbol ester PMA. These drugs
      exhibited the same effect on the basal promoter of the ferredoxin gene, which
      includes one TATA box and an SP1 site. In human adrenocortical cell line H295,
      the stimulation of the ferredoxin gene by cAMP was blocked by cycloheximide, as
      observed in bovine adrenocortical cell culture. In nonsteroidogenic cell lines
      such as HeLa and COS-1, the stimulation of ferredoxin gene expression by cAMP was
      not observed, although basal expression was strong. Transfection studies showed
      that the ferredoxin promoter could not be stimulated by cAMP in nonsteroidogenic
      cells. Therefore the steroidogenic cell-specific regulation and the general
      expression pattern appears to be a property unique to the ferredoxin gene.

PMID- 7626498
TI  - Developmental roles of the retinoic acid receptors.
AB  - Retinoic acid, one of the principle active metabolites of vitamin A (retinol), is
      believed to be essential for numerous developmental and physiological processes.
      Vitamin A deprivation (VAD) during development leads to numerous congenital
      defects. Previous studies of retinoic acid receptor (RAR) deficient mice failed
      to reveal any of these VAD-induced defects. This finding suggested that either
      the RARs are functionally redundant or that they are not critically required
      during development. In order to address these possibilities, we derived a number
      of RAR compound mutants. Unlike RAR single mutants, these compound null mutants
      died either in utero or shortly following birth. Histological analysis revealed
      essentially all of the defects characteristic of fetal VAD. A number of
      additional malformations, not described in previous VAD studies, were also
      observed. These included defects of the ocular and salivary glands and their
      ducts, the skeletal elements of the fore- and hindlimbs, and the cervical region
      of the axial skeleton. In addition, with the exception of derivatives forming
      within the first pharyngeal arch, most of the elements derived from mesectoderm
      emanating from cranial and hindbrain levels were affected. A number of these
      mutants also exhibited supernumerary cranial skeletal elements characteristics of
      the reptilian skull. A summary of the defects found in these RAR double mutants
      is presented.

PMID- 7626499
TI  - Definition of the critical cellular components which distinguish between hormone
      and antihormone activated progesterone receptor.
AB  - The steroid hormone progesterone is a key modulator of the cellular processes
      associated with the maintenance and development of female reproductive function.
      The biological activity of this hormone is mediated by specific nuclear receptors
      located in target cell nuclei which upon activation are capable of modulating the
      transcriptional activity of promoters containing progesterone response elements.
      Abnormalities in the progesterone receptor (PR) signal transduction pathway are
      implicated in pathological states such as breast cancer, endometriosis, and
      uterine fibroids. As a result of the medical need to modulate PR transcriptional
      activity, antiprogestins, compounds which oppose the actions of progesterone and
      novel progesterone receptor agonists, have been developed. This review outlines
      our current understanding of the critical cellular components which define the
      pharmacology of progesterone receptor agonists and antagonists, and how this
      information will impact the discovery and development of additional therapeutics.

PMID- 7626500
TI  - Enzymes and binding proteins affecting retinoic acid concentrations.
AB  - Free retinoids suffer promiscuous metabolism in vitro. Diverse enzymes are
      expressed in several subcellular fractions that are capable of converting free
      retinol (retinol not sequestered with specific binding proteins) into retinal or
      retinoic acid. If this were to occur in vivo, regulating the temporal-spatial
      concentrations of functionally-active retinoids, such as RA (retinoic acid),
      would be enigmatic. In vivo, however, retinoids occur bound to high-affinity,
      high-specificity binding proteins, including cellular retinol-binding protein,
      type I (CRBP) and cellular retinoic acid-binding protein, type I (CRABP). These
      binding proteins, members of the superfamily of lipid binding proteins, are
      expressed in concentrations that exceed those of their ligands. Considerable data
      favor a model pathway of RA biosynthesis and metabolism consisting of enzymes
      that recognize CRBP (apo and holo) and holo-CRABP as substrates and/or affecters
      of activity. This would restrict retinoid access to enzymes that recognize the
      appropriate binding protein, imparting specificity to RA homeostasis; preventing,
      e.g. opportunistic RA synthesis by alcohol dehydrogenases with broad substrate
      tolerances. An NADP-dependent microsomal retinol dehydrogenase (RDH) catalyzes
      the first reaction in this pathway. RDH recognizes CRBP as substrate by the dual
      criteria of enzyme kinetics and chemical crosslinking. A cDNA of RDH has been
      cloned, expressed and characterized as a short-chain alcohol dehydrogenase.
      Retinal generated in microsomes from holo-CRBP by RDH supports cytosolic RA
      synthesis by an NAD-dependent retinal dehydrogenase (RalDH). RalDH has been
      purified, characterized with respect to substrate specificity, and its cDNA has
      been cloned. CRABP is also important to modulating the steady-state
      concentrations of RA, through sequestering RA and facilitating its metabolism,
      because the complex CRABP/RA acts as a low Km substrate.

PMID- 7626501
TI  - Chicken ovalbumin upstream promoter transcription factor (COUP-TF): expression
      during mouse embryogenesis.
AB  - Members of the steroid/thyroid hormone receptor superfamily such as TR, RAR, RXR
      and VDR are known to play important roles in regulation of gene expression during
      development, differentiation and homeostasis. COUP-TFs are orphan members of this
      superfamily of nuclear receptors and have been shown to negatively regulate the
      ability of these nuclear receptors to transactivate target genes. Two different
      mechanisms are implicated in this repression. First, COUP-TFs bind to AGGTCA
      direct repeats and palindromes with various spacings, which include response
      elements for TR, RAR, RXR and VDR, allowing for direct competition of COUP-TFs
      for the response elements. Second, COUP-TFs can heterodimerize with RXRs, the
      essential cofactor for effective binding of VDR, TRs and RARs to their cognate
      response elements. The physiological significance of this negative effect of COUP
      TF on the activity of these receptors has been analyzed. Detection of COUP-TF
      transcripts during mouse development reveal discrete spatial and temporal
      expression domains consistent with COUP-TFs being involved in regulation of gene
      expression during embryogenesis. Transcripts are localized within discrete
      regions of the central and peripheral nervous system including the inner ear. In
      addition, COUP-TFs are found in many tissues including testes, ovary, prostate,
      skin, kidney, lung, stomach, intestine, pancreas and salivary gland. Some of
      these expression domains colocalize with those of TR, RAR, and RXR. The
      simultaneous expression of these genes raise the possibility that COUP-TFs can
      act as negative regulatory factors during development and differentiation.

PMID- 7626502
TI  - Phosphorylation and progesterone receptor function.
AB  - Four phosphorylation sites have been identified in the chicken progesterone
      receptor. Two of these sites exhibit basal phosphorylation which is enhanced upon
      treatment with hormone and two of the sites are phosphorylated in response to
      hormone. Mutation of one of these hormone dependent sites, Ser530 to Ala530,
      causes a decrease in transcriptional activation at low concentrations of hormone,
      but the activity is unaffected at high concentrations. However, the hormone
      binding of the mutant is unaffected suggesting that phosphorylation of Ser530
      plays a role in facilitating the response of the receptor to low concentrations
      of hormone. The chicken progesterone receptor can be activated by modulators of
      kinases in the absence of hormone. The finding that signals initiated by tyrosine
      phosphorylation (through treatment with EGF) or through the dopamine receptor
      suggests that there are multiple means of activating chicken progesterone
      receptor. In contrast, the human progesterone receptor does not exhibit ligand
      independent activation; however, its activity in the presence of the agonist
      R5020 is enhanced by treatment with 8-Br-cAMP, an activator of protein kinase A,
      and treatment with 8-Br-cAMP causes the antagonist, RU486, to act as an agonist.

PMID- 7626503
TI  - Structure and function of corticosteroid-binding globulin: role of carbohydrates.
AB  - To study the site-specificity of human corticosteroid-binding globulin (CBG)
      glycosylation and the functional significance of individual carbohydrate chains
      in its molecule, a panel of recombinant CBG mutants containing each of the six
      potential glycosylation sites alone and in various combinations has been
      expressed in Chinese hamster ovary (CHO) cells. Analyses of these mutant
      glycoproteins showed that three of the glycosylation sites are only partially
      utilized, and this may contribute to the production of glycoforms with distinct
      physiological functions. Processing of individual carbohydrate chains (branching
      and fucosylation) is site-specific and may, thus, account for the formation of
      structural determinants essential for the recognition of CBG by cell membranes.
      Glycosylation at the only phylogenetically conserved consensus site, Asn238
      Gly239-Thr240, is essential for the biosynthesis of CBG with steroid-binding
      activity. Evidence has been obtained to support the hypothesis that transient
      carbohydrate-polypeptide interactions between Trp266 and the maturing
      carbohydrate chain at Asn238 occur during early stages of the CBG biosynthesis
      which affect protein folding and formation of the steroid-binding site. Another
      tryptophan residue, Trp371, has been found to be critical for CBG-steroid
      interactions and is likely located in the steroid-binding site.

PMID- 7626504
TI  - Corticosteroid-binding globulin (CBG) in fetal development.
AB  - In fetal sheep the prepartum increase in plasma cortisol concentration is
      associated with an increase in high affinity corticosteroid binding activity in
      plasma. This appears to reflect an increase in corticosteroid-binding globulin
      (CBG) biosynthesis from the fetal liver, and evidence is presented that hepatic
      CBG gene expression is increased by exposure to glucocorticoids in the fetus.
      Immunoreactive CBG is found in other fetal tissues, and CBG mRNA is present in
      fetal pituitary. CBG reduces the ability of cortisol to exert negative feedback
      on basal or CRH-stimulated ACTH output by fetal sheep pituitary cells in culture.
      We suggest that CBG interacts with cortisol in a manner that maintains a low
      negative feedback on the pituitary, and perhaps hypothalamus. This constitutes a
      component of the cascade of events that is associated with hypothalamic-pituitary
      adrenal activation in the late gestation fetus, and with the onset of
      parturition.

PMID- 7626505
TI  - Sex hormone-binding globulin and female reproductive function.
AB  - Although sex steroids have long been known to influence serum concentrations of
      SHBG, it is now recognized that nutritional factors may be more important in the
      regulation of SHBG in women. Thus, SHBG concentrations are negatively correlated
      with body mass index (BMI) and, more particularly, to indices of central
      adiposity. Polycystic ovary syndrome (PCOS), the most common cause of anovulatory
      infertility, is associated with truncal obesity, hyperandrogenism and
      hyperinsulinaemia. There is evidence that insulin may be the humoral mediator of
      the weight-dependent changes in SHBG. Serum SHBG concentrations are inversely
      correlated with both fasting and glucose-stimulated insulin levels, and insulin
      has been shown to have a direct inhibitory effect on SHBG synthesis and secretion
      by hepatocytes in culture. However, the interrelationship of BMI, insulin and
      SHBG appears to be different in women with PCOS from that in normal subjects. The
      clinical importance of the weight-related suppression of SHBG is illustrated by
      the finding of a greater prevalence of hirsutism in obese women PCOS compared
      with their lean counterparts. Obese subjects with PCOS have similar total
      testosterone concentrations to lean PCO women but have lower SHBG and
      reciprocally higher free testosterone levels. Calorie restriction results in
      reduction of serum insulin followed by an increase in SHBG and a fall in free
      testosterone but an isocaloric, low-fat diet has no significant effect on SHBG
      concentrations. Weight reduction in obese, hyperandrogenaemic women with PCO is
      an important approach to the management of both anovulation and hirsutism.

PMID- 7626506
TI  - Mineralocorticoid receptors and hypertension.
AB  - Mineralocorticoid receptors (MR) have equal affinity for the mineralocorticoid
      aldosterone, and the physiological glucocorticoids cortisol and corticosterone.
      In epithelial tissues in vivo, MR are protected against glucocorticoid occupancy
      by the enzyme 11 beta-hydroxysteroid dehydrogenase, allowing access by the lower
      circulating levels of the physiological mineralocorticoid aldosterone. In non
      epithelial tissues, including the heart and most areas of the central nervous
      system, MR are not so protected, and their physiological ligand is
      cortisol/corticosterone. Intracerebroventricular infusion studies have shown that
      aldosterone occupancy of such unprotected circumventricular MR is necessary for
      mineralocorticoid hypertension, and the hypertensinogenic effects of peripherally
      infused aldosterone can be blocked by intracerebroventricular infusion of the MR
      antagonist RU28318. Prolonged (8 weeks) administration of mineralocorticoids to
      salt-loaded rats has been shown to be followed by hypertension, cardiac
      hypertrophy and cardiac fibrosis. Whether the hypertrophy and fibrosis reflect
      primary effects of aldosterone via cardiac MR, or effects secondary to occupancy
      of protected, epithelial MR, remains to be determined, as does the mechanism of
      action of salt loading in this model of mineralocorticoid hypertension.

PMID- 7626507
TI  - Endocytosis of androgen-binding protein (ABP) by spermatogenic cells.
AB  - To test whether Sertoli cell-secreted ABP could serve as steroid carrier to the
      germ cell (GC) lineage, radiolabeled ABP and SHBG and gold SHBG were used for
      binding studies and for internalization studies based on transmission electron
      microscope analyses and autoradiography of the radiolabeled samples. The data
      clearly showed that: (1) rat and human germ cells possess a single class of
      binding sites for rat ABP and human SHBG respectively (Kd of 0.78 and 0.56 nM);
      (2) 1.7 x 10(10) and 2.7 x 10(10) sites/mg protein was found in the corresponding
      plasma membrane preparations; (3) the receptor peak was eluted in the same
      position as dextran blue: 2000 kDa (M(r) = 2 x 106) for labeled rat ABP; (4) in
      the whole GC lineage, the labeled ligand was internalized through an endocytic
      pathway involving clathrin coated structures and the distribution was similar
      throughout the maturation step, however striking differences in the
      internalization rate were revealed with regard to the maturation step; and (5)
      this internalization occurred even in ligated seminiferous tubules, via the
      Sertoli cells cytoplasm. When isolated rat GC were incubated in the presence of
      ABP, a dose dependent increase in labeled secreted protein was observed for
      spermatocytes (50-250%) whereas ABP had no effect on spermatids. Addition of
      steroids and ABP caused a 200 and 50% increase in labeled secreted proteins for
      spermatocytes and spermatids respectively. 2-D SDS-PAGE analysis revealed that
      ABP alone increased the secretion of specific spermatocyte proteins whereas
      steroids in the presence of ABP resulted in the synthesis of new spermatocyte
      secreted proteins. Taken together these results strongly suggest that ABP may be
      required for spermatogenesis either as a steroid transmembrane carrier or on its
      own.

PMID- 7626508
TI  - Sex hormone-binding globulin/androgen-binding protein: steroid-binding and
      dimerization domains.
AB  - Plasma sex hormone-binding globulin (SHBG) and testicular androgen-binding
      protein (ABP) are homodimeric glycoproteins that share the same primary
      structure, and differ only with respect to the types of oligosaccharides
      associated with them. The biological significance of these differences is not
      understood, but enzymatically deglycosylated SHBG and a non-glycosylated SHBG
      mutant both bind steroids normally. Various affinity-labelling experiments, and
      studies of recombinant SHBG mutants have indicated that a region encompassing and
      including Met-139 in human SHBG represents an important component of its steroid
      binding site. Analyses of chimeric proteins comprising various portions of human
      SHBG and rat ABP have also indicated that residues important for the much higher
      affinity of human SHBG for steroid ligands are probably located within the N
      terminal portion of these molecules. Recent studies of SHBG mutants have
      confirmed this, and a deletion mutant containing only the first 205 N-terminal
      residues of human SHBG has been produced which dimerizes and binds steroids
      appropriately. The introduction of amino-acid substitutions between Lys-134 and
      Phe-148 of SHBG has also indicated that residues including and immediately N
      terminal of Met-139 may influence steroid-binding specificity, while those
      immediately C-terminal of Met-139 represent at least a part of the dimerization
      domain. These studies have also demonstrated that dimerization is induced by the
      presence of steroid ligand in the binding site, and that divalent cations play an
      important role in this process. Together, these data have led us to conclude that
      SHBG is a modular protein, which comprises an N-terminal steroid-binding and
      dimerization domain, and a C-terminal domain containing a highly-conserved
      consensus sequence for glycosylation that may be required for other biological
      activities, such as cell-surface recognition.

PMID- 7626509
TI  - Genetic variations in human testosterone-estradiol binding globulin.
AB  - The human testosterone-estradiol-binding globulin (hTeBG) is a plasma
      heterogeneous glycoprotein with high affinity for a number of circulating steroid
      hormones. The heterogeneity originates from differential glycosylation of a
      common protein precursor. Analysis of desialylated hTeBG by isoelectric focusing
      (IEF) has revealed that microheterogeneity could be partly attributed to
      variability in sialic acid content or rearrangement of amino acid composition. We
      have studied this possibility by the analysis of desialylated serum hTeBG by
      Western blotting of proteins previously separated on IEF-gels. Two distinct well
      defined IEF patterns were identified. The most frequent consisted of two major
      IEF-bands of equal color intensity. The other pattern consisting of four IEF
      bands was present in only 5.55% of the total serum samples analyzed. Family
      studies showed that these phenotypes were autosomally inherited with a simple
      Mendelian transmission and allele frequencies had an excellent agreement between
      the observed and expected phenotypes. Androgen affinity constants and serum
      concentrations of hTeBG variant were similar to those of normal hTeBG. Molecular
      analyses of each of the exons of hTeBG gene by denaturing gradient gel
      electrophoresis revealed the presence of a point mutation in exon 8. The studies
      presented herein confirm and extend previous reports on the existence of
      structural variants of hTeBG. In addition, the mutation reported in this study is
      probably the same as that recently identified within numerous ethnic groups
      throughout the world, thus further supporting the concept of a two allele gene
      worldwide concoding hTeBG.

PMID- 7626510
TI  - Receptors for androgen-binding proteins: internalization and intracellular
      signalling.
AB  - In plasma, most steroid hormones are bound and transported by the specific
      binding protein, testosterone-estradiol-binding globulin (TeBG). For years, it
      was believed that the only function of this protein was to regulate the
      concentration of free steroids in plasma. However, a number of reports have
      provided evidence for the presence of specific TeBG receptors on plasma
      membranes. Furthermore, the interaction of TeBG with its receptor was shown to be
      inhibited when steroids are bound to TeBG, suggesting that TeBG is an allosteric
      protein. The purpose of this manuscript is to review the evidence that androgen
      binding proteins bind to membrane receptors, and, in some cells, this binding
      stimulates cAMP accumulation, and transfer TeBG/ABP into tissue as a consequence
      of receptor mediated endocytosis. Recent studies from our laboratories have
      demonstrated binding and uptake of TeBG by MCF-7 breast cancer cells. The
      interaction of unligated rabbit TeBG with membranes from MCF-7 cells resulted in
      a time and concentration-dependent increase in adenylate cyclase activity. The
      TeBG alone also had a reproducible effect on intact cells by increasing cAMP
      accumulation by 30-35%. The addition of DHT to cells, after TeBG has been allowed
      to bind, resulted in increases in cAMP of greater than 4-fold. This effect was
      not blocked by antiandrogens. These data support the hypothesis that
      extracellular SHBG is a regulator of cellular function through a membrane
      receptor that is coupled to adenylate cyclase.

PMID- 7626511
TI  - Interrelations between sex hormone-binding globulin (SHBG), plasma lipoproteins
      and cardiovascular risk.
AB  - The incidence of coronary artery disease is significantly higher in men than in
      women, at least until menopause. This gender difference could be explained by the
      action of sex steroids on the lipoprotein profile. In prepubertal children, high
      density lipoprotein (HDL) cholesterol and triglyceride levels are similar between
      sexes, while adult men have generally lower HDL cholesterol and higher
      triglyceride levels than premenopausal adult women. Most cross-sectional studies
      have reported that sex hormone binding globulin (SHBG) and testosterone levels
      correlate positively with HDL cholesterol levels between sexes. Thus SHBG by
      modulating the balance in the biodisposal of testosterone and estradiol, might
      have a profound effect on the risk of cardiovascular disease. However, adjustment
      for body weight and body fat distribution weakens the association between SHBG,
      testosterone and HDL cholesterol. The negative correlation of fasting insulin
      with SHBG and HDL cholesterol levels in both sexes, and some evidence that
      insulin is an inhibitor of SHBG production in vitro, has suggested that
      hyperinsulinism might negatively regulate SHBG and HDL levels. It remains to be
      determined whether the inverse relationship between SHBG and insulin levels is
      coincidental or has a causal effect on the increase of atherosclerosis. Decreased
      SHBG has been shown to be predictive of the incidence of non-insulin-dependent
      diabetes mellitus in women but not in men, and of subsequent development of
      cardiovascular disease and overall mortality in postmenopausal women. SHBG is an
      index of androgenism in women and of insulin-resistance in both sexes, and might
      be useful in epidemiological studies of cardiovascular risk. However, in men,
      SHBG is not predictive of the occurrence of cardiovascular disease. Whether SHBG
      might have an intrinsic protective effect on the arterial wall through SHBG
      receptors is still highly speculative.

PMID- 7626512
TI  - Androgen binding protein is tissue-specifically expressed and biologically active
      in transgenic mice.
AB  - In view of the inconclusive data concerning the role of androgen-binding protein
      (ABP) in male reproductive physiology, we thought it would be pertinent to make
      several transgenic mouse lines overexpressing the rat ABP gene to unravel its
      role in Sertoli cell and epididymal homeostasis. Heterozygote transgenic mouse
      lines carrying the 5.5 kb ABP rat genomic DNA were produced by pronuclear
      microinjection. Northern blot analysis showed overexpression of rat ABP (rABP)
      mRNA in the testis of transgenic mice compared to rat testis control. rABP was
      appropriately expressed in Sertoli cells as demonstrated by in situ hybridization
      analysis. Sertoli cell number is increased in the seminiferous tubules of mice
      overexpressing rABP compared to non-transgenic littermates and scattered Sertoli
      cells present vacuolated-like cytoplasms, PAS and osmium negative. Compared to
      the wild type, the transgenic mice exhibited reduced fertility and focal damage
      in seminiferous epithelium characterized by morphological features compatible
      with programmed cell death.

PMID- 7626513
TI  - Plasma vitamin D-binding protein (Gc-globulin): multiple tasks.
AB  - The transporter of vitamin D and its metabolites in blood has received increasing
      attention in recent years, and is recognized to be a member of a gene family that
      includes albumin and alpha-fetoprotein. Identical to the group specific component
      (Gc-globulin) of serum, the protein is a single-chain polypeptide constitutively
      synthesized in liver that circulates in amounts in far excess of normal vitamin D
      metabolite concentrations in blood. It plays the major role in the egress of
      endogenously synthesized vitamin D, from skin and appears to restrain D-sterols
      from too rapid/excessive cell entry. Along with plasma gelsolin, it comprises the
      plasma actin-scavenger system that facilitates removal of actin, liberated from
      lysed cells, by depolymerization and prevention of polymerization. Recently, the
      protein has been shown to behave as a co-chemotaxin specific for the complement
      peptide C5a, and its sialic acid-free form has been reported to play a role in
      macrophage activation. The latter functions strongly implicate its participation
      in inflammation responses. A unifying hypothesis might also suggest the protein
      to provide focal D-sterol delivery to cells that are important to the resolution
      of tissue injuries.

PMID- 7626514
TI  - Receptor mediated genomic action of the 1,25(OH)2D3 hormone: expression of the
      human vitamin D receptor in E. coli.
AB  - The nuclear vitamin D receptor (VDR) binds the 1,25-dihydroxyvitamin D3
      (1,25(OH)2D3) hormone with high affinity and elicits its actions to stimulate
      gene expression in target cells by binding to the vitamin D-responsive element
      (VDRE). VDREs in such positively controlled genes as osteocalcin, osteopontin,
      beta 3 integrin and vitamin D-24-OHase are direct hexanucleotide repeats with a
      spacer of three nucleotides. The present studies of VDR/VDRE interaction utilized
      full-length human vitamin D receptor (hVDR) that was overexpressed in E. coli,
      purified to near homogeneity (> 95%), and its authenticity confirmed by
      demonstrating high affinity hormone binding and reactivity to monoclonal antibody
      9A7 gamma. The expressed hVDR displays strict dependence on the family of
      retinoid X receptors (RXRs) for binding to the vitamin D-responsive element
      (VDRE) in the rat osteocalcin gene. Similar overexpression in E. coli of the DNA
      binding domain (delta 134), containing only residues 4-133 of hVDR, generated a
      receptor species that possesses intrinsic DNA binding activity. Both full-length
      and delta 134 hVDRs retain similar DNA binding specificities when tested with
      several natural hormone responsive elements, indicating that the N-terminal zinc
      finger region determines hVDR-DNA sequence selectivity. The C-terminal region of
      the molecule is required for hormone binding and confers the receptor with the
      property of very high affinity DNA binding, via heterodimerization between hVDR
      and RXR. A natural ligand for the RXR co-receptor, 9-cis retinoic acid,
      suppresses both VDR-RXR binding to the VDRE and 1,25(OH)2D3 stimulated
      transcription, indicating that 9-cis retinoic acid recruits RXR away from VDR to
      instead form RXR homodimers.

PMID- 7626515
TI  - Regulation of the ferredoxin component of renal hydroxylases at transcriptional
      and postranslational levels and of the protein inhibitor of cyclic AMP-dependent
      kinase.
AB  - We have studied two proteins potentially involved in the regulation of the 25-OH
      D-1-hydroxylase, which is located in the renal mitochondria and which is
      responsible for the production of the steroid hormone 1,25(OH)2D3. The endogenous
      inhibitor of cyclic AMP-dependent protein kinase, PKI, is down regulated by
      1,25(OH)2D3. Having cloned and sequenced PKI cDNA, we studied its message levels
      and found them to be regulated by 1,25(OH)2D3 tissue specifically in the kidney
      and in kidney cell culture. In other experiments we over expressed the ferredoxin
      component of the 1-hydroxylase and found it to be physically and chemically
      indistinguishable from those of classic steroidogenic tissues. The mRNA encoding
      the ferredoxin component is up-regulated by chronic vitamin D deficiency, which
      at the same time leads to sustained elevation in 1-hydroxylase activity; no short
      term effect of 1,25(OH)2D3 on ferredoxin mRNA in kidney cell culture could be
      demonstrated. Finally, there was an association between decreased phosphorylation
      of ferredoxin and decreased 1-hydroxylase activity brought about by treatment of
      cultured kidney cells with TPA. Control of the renal signaling events involved in
      the production of 1,25(OH)2D3 remains a fruitful area of investigation in the
      field of the metabolism and actions of vitamin D and its metabolites.

PMID- 7626516
TI  - Immunomodulatory actions of 1,25-dihydroxyvitamin D3.
AB  - The sterol, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), has immunosuppressive
      activity. The hormone inhibits the production of lymphokines (IL-2, IFN-gamma)
      and monocyte-derived cytokine (IL-12) leading to inhibition of helper T cell
      subset type 1 (Th1). When given in vivo, the hormone prevents the development of
      spontaneous and induced models of autoimmunity. Analogs of 1,25(OH)2D3, with
      reduced hypercalcemic effects, display an enhanced activity in autoimmunity
      compared to the sterol and prolong graft survival in experimental
      transplantation. This paper reviews our understanding of the cellular actions of
      the hormone and the therapeutic application of 1,25(OH)2D3 and analogs in
      autoimmunity and transplantation.

PMID- 7626517
TI  - Chemistry and conformation of vitamin D molecules.
AB  - 1 alpha,25-Dihydroxyvitamin D3 (1,25) is a structurally unique steroid hormone
      because it not only possesses the complete 25-hydroxycholesterol side chain, but
      most notably, it possesses a seco-B triene structure (it lacks a B-ring and is
      usually depicted in a non-steroidal, extended conformation). In contrast, the
      classical steroid hormones possess a truncated side chain (progesterone,
      cortisol, and aldosterone) or no side chain (estradiol and testosterone) and they
      all possess the fully intact ABCD steroid rings. These structural differences
      render the seco-B-steroid 1,25 considerably more conformationally flexible. Since
      1,25 is now known to target a myriad of tissues where specific interactions occur
      to produce an array of biological responses, it is of interest to determine
      whether different topologies of 1,25 (resulting from different conformational
      orientations of 1,25) are necessary to interact effectively at the different
      target sites. The array of biological responses include both non-genomic and
      genomic effects and there is considerable promise for the efficacy of 1,25
      analogs as chemotherapeutic agents in a variety of human disease states. For the
      non-genomic calcium transport response of transcaltachia, the finding that two 6
      s-cis locked analogs, 1 alpha,25-dihydroxyprevitamin D3 (pre-1,25) and 1 alpha,25
      dihydroxylumisterol3 (1,25-Lumi), are equipotent to 1,25, points strongly to the
      involvement of the 6-s-cis conformer of 1,25 as the biologically active
      conformer. Since there is a continuum of easily interconvertible 6,7-single bond
      conformers of the seco-B ring available to 1,25, conformational minima (either
      local or global) may have little to do with the manner in which 1,25 is bound to
      receptor. For the genomic calcium transport response, and for other genomic (or
      non-genomic) effects, there is no clear evidence whether the steroidal (s-cis) or
      non-steroidal (s-trans) conformer of 1,25 is involved. In order to address this
      matter further, efforts are underway to evaluate other conformationally locked
      analogs of 1,25 which might mimic either the planar 6-s-trans-1,25 or some
      intermediate conformer between it and the planar-6-s-cis form.

PMID- 7626518
TI  - Differentiation of adult Leydig cells.
AB  - Adult Leydig cells originate within the testis postnatally. Their formation is a
      continuous process involving gradual transformation of progenitors into the
      mature cell type. Despite the gradual nature of these changes, studies of
      proliferation, differentiation and steroidogenic function in the rat Leydig cell
      led to the recognition of three distinct developmental stages in the adult Leydig
      cell lineage: Leydig cell progenitors, immature Leydig cells and adult Leydig
      cells. In the first stage, Leydig cell progenitors arise from active
      proliferation of mesenchymal-like stem cells in the testicular interstitium
      during the third week of postnatal life and are recognizable by the presence of
      Leydig cell markers such as histochemical staining for 3 beta-hydroxysteroid
      dehydrogenase (3 beta-HSD) and the present of luteinizing hormone (LH) receptors.
      They proliferate actively and by day 28 postpartum differentiate into immature
      Leydig cells. In the second stage, immature Leydig cells are morphologically
      recognizable as Leydig cells. They have an abundant smooth endoplasmic reticulum
      and are steroidogenically active, but primarily produce 5 alpha-reduced androgens
      rather than testosterone. Immature Leydig cells divide only once, giving rise to
      the total adult Leydig cell population. In the third and final stage, adult
      Leydig cells are fully differentiated, primarily produce testosterone and rarely
      divide. LH and androgen act together to stimulate differentiation of Leydig cell
      progenitors into immature Leydig cells. Preliminary data indicate that insulin
      like growth factor-1 (IGF-1) acts subsequently in the transformation of immature
      Leydig cells into adult Leydig cells.

PMID- 7626519
TI  - Steroid hormones upregulate rat angiotensin II type 1A receptor gene: role of
      glucocorticoid responsive elements in rat angiotensin II type 1A promoter.
AB  - The transcription of the rat angiotensin II type 1A receptor gene is stimulated
      by glucocorticoids. To clarify the molecular mechanism for glucocorticoid action
      in rat vascular smooth muscle cells, we investigated the effects of dexamethasone
      on the promoter activity of the angiotensin II type 1A receptor by using
      promoter/luciferase reporter gene constructs and heterologous context constructs
      (containing the thymidine kinase promoter) in transfected vascular smooth muscle
      cells. There are three putative glucocorticoid responsive elements in the
      promoter. However, only one glucocorticoid responsive element was found to
      respond to dexamethasone (1 microM). The region was located at positions, -756 to
      -770 bp upstream of the transcription initiation site. A glucocorticoid
      antagonist, RU38486, completely blocked the induction by dexamethasone,
      suggesting that the glucocorticoid responsive element was functional through a
      specific glucocorticoid receptor. Compared with the angiotensin II type 1A
      receptor promoter, no effect by dexamethasone was observed in vascular smooth
      muscle cells transfected with the angiotensin II type 1B receptor
      promoter/luciferase reporter gene constructs. We concluded that the dexamethasone
      induced increase in the transcription of the angiotensin II type 1A receptor gene
      occurred through the binding to GRE up the glucocorticoid-specific receptor.

PMID- 7626520
TI  - Regulation of adrenocortical steroidogenesis by benzodiazepines.
AB  - Benzodiazepines affect steroidogenesis in at least four ways depending on
      concentration and adrenocortical cell type. Firstly, at micromolar
      concentrations, they inhibit steroidogenic enzymes. Competition for microsomal 17
      and 21-hydroxylase activity explains the inhibition of ACTH-stimulated
      aldosterone and cortisol synthesis by diazepam and midazolam. At slightly higher
      concentrations, we have evidence that 11 beta-hydroxylase activity is also
      inhibited. Secondly, at sub-micromolar concentrations, calcium influx is
      inhibited. T-type and L-type calcium channels appear to be blocked, this impairs
      signal response coupling and, in particular, decreases angiotensin- and K(+)
      stimulated aldosterone synthesis in zona glomerulosa cells. Thirdly, the
      mitochondrion of steroidogenic tissues is a sensitive site for the stimulatory
      effects of benzodiazepines. Aldosterone synthesis from added HDL-cholesterol by
      cultured bovine zona glomerulosa cells is stimulated by diazepam, RO5-4864 and
      PK11195. The fourth site of benzodiazepine's effect on steroidogenesis is
      particular to zona glomerulosa cells. In addition to cholesterol side chain
      cleavage, the final part of the aldosterone biosynthetic pathway, the conversion
      from deoxycorticosterone is controlled. Although high micromolar concentrations
      of diazepam appear to be inhibitory, lower nanomolar concentrations stimulate the
      synthesis of aldosterone from added deoxycorticosterone. In vivo, a fifth site of
      benzodiazepine activity may influence plasma steroid concentrations. Competition
      between steroids and benzodiazepines for hepatic clearance enzymes may affect
      half lives of both drugs and hormones.

PMID- 7626521
TI  - Function and distribution of a steroidogenic cell-specific transcription factor,
      Ad4BP.
AB  - Ad4BP was identified as an essential transcription factor regulating
      steroidogenic cell-specific and cAMP-dependent transcription of the genes of
      steroidogenic P450s. The Ad4BP transcript was detected in steroidogenic tissues
      such as adrenal gland, testis, ovary, placenta and brain by RT-PCR, and showed
      good correlation with the expression of steroidogenic P450s. The genes of
      steroidogenic P450s, which are transcribed only in steroidogenic cells, were
      transcribed in non-steroidogenic cells when an Ad4BP expression vector was
      introduced into the cells. To study the function of Ad4BP in the differentiation
      of the steroidogenic tissues, immunochemical and immunohistochemical studies were
      performed with the tissues prepared from various developmental stages of rats.
      Adrenal cortex expressed Ad4BP since the tissue was detected in the dorsal wall
      of the fetus. Gonadal tissues expressed Ad4BP in a sex-dependent manner. High
      levels of Ad4BP expression were detected in fetal and prepubertal testes and in
      prepubertal and adult ovaries, whereas low level expressions were observed in the
      adult testes and in the fetal ovaries. The expression of Ad4BP in the gonads
      correlates well with the expression of the Mullerian inhibiting substance gene as
      well as the steroidogenic P450 gene for both sexes. These observations indicate
      that Ad4BP plays an important role in the development and differentiation of the
      steroidogenic tissues including sexual differentiation of the gonadal tissues
      through activation of the transcription of its target genes.

PMID- 7626522
TI  - Cytochrome P450(11 beta): structure-function relationship of the enzyme and its
      involvement in blood pressure regulation.
AB  - Cytochrome P450(11 beta) is deeply involved in the final steps of biosynthesis of
      mineralocorticoids. This paper deals with following issues about this enzyme. (1)
      The structure and function of the enzymes of various animal species are
      discussed. By making alignment of amino acid sequences of the enzymes, we
      identified peptide domains essential for the enzyme actions such as a putative
      steroid binding domain and a heme binding region. Estimates of molecular
      similarity among the P450(11 beta) family enzymes suggested that the enzymes
      having both 11 beta-hydroxylation activity and aldosterone (ALDO) synthetic
      activity of certain animals such as frog, cattle and pig are more similar to the
      ALDO synthases of the other animals, such as rat, mouse and human, than the 11
      beta-hydroxylases of these animals. (2) The molecular nature of the P450(11 beta)
      family enzymes of genetically hypertensive rats as well as adrenal regeneration
      hypertension (ARH) rats is examined. (i) Mutation was found in the P450(11 beta)
      gene of Dahl's salt-resistant normotensive rat. Steroidogenic activity expressed
      by the mutated gene accounted well for abnormal plasma levels of steroid hormones
      in this rat. (ii) 11 beta-, 18- and 19-Hydroxylation activities of adrenal
      mitochondrial prepared from spontaneously hypertensive rat (SHR), Wistar-Kyoto
      rat (WKY), and stroke-prone (SP)-SHR were not significantly different from each
      other. Levels of mRNA of ALDO synthase in adrenal glands of 50-week-old SHR was
      significantly lower than those of 10-week-old SHR, WKY and SHR-SP. (iii) No
      significant difference in 19-hydroxylation activity was found between adrenal
      mitochondria prepared from ARH rat and those from control rat. The level of
      message of ALDO synthase was lower in adrenal glands of ARH rat.

PMID- 7626523
TI  - Novel mechanisms of antiprogestin action.
AB  - When hormone antagonists have unexpected agonist-like effects, the clinical
      consequences are grave. We describe novel molecular mechanisms by which
      antiprogestin-occupied progesterone receptors behave like agonists. These
      mechanisms include agonist-like transcriptional effects that do not require
      receptor binding to DNA at progesterone response elements, or that result from
      cross-talk between progesterone receptor and other signalling pathways. We
      discuss the complex structural organization of progesterone receptors and
      demonstrate that the B-receptor isoform has a unique third activation domain that
      may confer agonist-like properties in the presence of antiprogestins. By
      contrast, the A-receptor isoform is a dominant-negative inhibitor. We argue that
      these novel mechanisms play a role in the apparent hormone resistance of breast
      cancers and the variable tissue-specific responses to progestins.

PMID- 7626524
TI  - Comparison of protein phosphorylation patterns produced in adrenal cells by
      activation of cAMP-dependent protein kinase and Ca-dependent protein kinase.
AB  - Bovine adrenal fasciculata cells, exposed to either ACTH or AII, synthesize
      glucocorticoids at an enhanced rate. It is generally accepted that the signaling
      pathways triggered by these two peptides are not identical. ACTH presumably acts
      via a cAMP-dependent protein kinase (PKA) and AII, via a calcium-dependent
      protein kinase. We have found that either peptide hormone stimulates synthesis of
      a mitochondrial phosphoprotein pp37, leading to accumulation of its
      proteolytically processed products pp30 and pp29. On the basis of a number of
      criteria, this 37 kDa protein is the bovine homolog of the 37 kDa protein that we
      have characterized in rodent steroidogenic tissue (Epstein L. F. and Orme-Johnson
      N. R.: J. Biol. Chem 266 (1991) 19,739-19,745). Further, bovine pp37 is
      phosphorylated when PKA or protein kinase C (PKC) is activated directly by (Bu)2
      cAMP or PMA, respectively. These studies indicate that either pp37 is a common
      substrate for PKA and PKC in these cells or there is a common downstream kinase,
      which is activated by exposure to either ACTH or AII. Rat adrenal glomerulosa
      cells, exposed to either ACTH or AII, show an enhanced rate of mineralocorticoid
      synthesis. As for bovine fasciculata cells, it is thought that the signaling
      pathway triggered by ACTH differs from that triggered by AII. As we found for
      bovine fasciculata, pp37 is phosphorylated when the rat cells are exposed to
      either peptide hormone. However, in contrast to the finding for bovine
      fasciculata, while exposure of the rat glomerulosa cells to (Bu)2cAMP does cause
      the synthesis of pp37, exposure of the cells to PMA does not. Taken together,
      these findings provide further evidence that the subcellular signaling events,
      triggered by the action of AII on bovine adrenal fasciculata and rat adrenal
      glomerulosa cells, differ. Further, the fact, that pp37 is phosphorylated only
      when the rate of steroidogenesis is enhanced, reaffirms its potential involvement
      in the signaling pathway that causes stimulation of steroid hormone biosynthesis.

PMID- 7626525
TI  - Isolation and characterization of the exo-enterotoxin of Vibrio cholerae strain
      110 Cal.
AB  - Vibrio Cholerae "strain 110 Cal" from Calabar, Nigeria were grown in syncase
      broth. Exo-enterotoxin secreted into the medium was then isolated purified and
      characterized. The toxin had enterotoxic activity using the infant mouseassay of
      World Health Organization. The toxin also had a molecular weight of about 89,000
      daltons by gel filtration through sephadex G-150 and 100,000 daltons by
      polyacrylamide gel electrophoresis (PAGE). The toxin exhibited two subunits with
      molecular weights of about 63,000 and 31,000 daltons on SDS-PAGE. The toxin was
      resolved through sephadex G-150 into three peaks having molecular weights of
      about 89,000, 44,000 and 14,000 daltons respectively. The three peaks had
      enterotoxic activity. Each peak contained a single protein band on PAGE and SDS
      PAGE showed that peak I consisted of two subunits with molecular weights of
      56,000 and 31,000 daltons and peak II and III were monomers.

PMID- 7626526
TI  - A simple mass-closure technique compared with layered technique in the closure of
      high-risk abdominal wounds.
AB  - A retrospective comparison of the outcome of patients with ruptured gravid uterus
      following obstructed labour who had abdominal closure by a simple mass-closure
      technique (using non-absorbable Nylon suture) with their counterparts who had the
      more popularly used layered technique. The clinical features on admission,
      operation details and wound complications were compared. Thirty-one patients who
      had mass-closure were compared with 103 that had the layered technique. Nineteen
      percent of the former had wound infections or partial dehiscences while none had
      complete dehiscence or hernias. On the other hand these respective complications
      occurred in 32%, 9.7% and 1.9% of the layered group. This mass-closure technique
      has the advantages of low-cost, speed and safety. We advocate that it be used on
      all high-risk abdominal wounds.

PMID- 7626527
TI  - Neonatal jaundice in Zaria, Nigeria--a second prospective study.
AB  - Of the 587 neonates born in ABUTH, Zaria, Nigeria and successfully followed up,
      99 were clinically jaundiced (16.9%). Of these, only 38 (38%) had significant
      hyperbilirubinaemia (serum bilirubin above 170 umol/L). During the same period,
      279 neonates were admitted through Emergency Paediatric Unit (EPU) of whom 70
      (25%) were jaundiced and 64 (95%) of them had serum bilirubin above 170 umol/L.
      Jaundice was more severe and the incidence of kernicterus higher in babies born
      outside the hospital than in those born in hospital and periodically followed up.
      The incidence of kernicterus was 20.3% and 2.6% respectively. The pattern of
      aetiological factors was similar in the two groups of jaundiced neonates.
      Septicaemia (50%) and G6PD deficiency (40%) were the major aetiological factors.
      Exposure to traditional herbal medications, oxytocin induced/augmented labour,
      cephalhaematoma and tribal incidences did not play statistically significant
      roles. Jaundice due to Rh-incompatibility was not encountered. Results of this
      double prospective study were compared with the previous findings in this and
      other centres in Nigeria.

PMID- 7626528
TI  - Utilization of maternal health services in Ejisu District, Ghana.
AB  - A study on the utilization of maternal health services in Ejisu district of Ghana
      was carried out in January and February 1990. 1200 women aged between 15 and 49
      were interviewed in 80 communities. The findings of the study indicated that over
      50% of respondents married under 20 years, 70% of them attended antenatal clinic
      at least 4 times in their last pregnancy, over 80% had their last delivery in a
      health facility and over 80% knew about at least one modern method of family
      planning. Only 5.5% were currently using a modern family planning method. 90% of
      them were willing to stay in a maternity waiting home if advised to do so. Most
      would be prepared to stay for a month or 2. 20% of the respondents knew about
      local herbal preparations used for first aid in bleeding in pregnancy, although
      they would seek definitive treatment at a health facility. From the study, some
      women were not using the services. These would have to be reached through
      improving the quality of care in health facilities and increasing community
      awareness on maternal health in order to improve accessibility and utilization
      further.

PMID- 7626529
TI  - The CERAD Neuropsychological Test Battery: norms from a Yoruba-speaking Nigerian
      sample.
AB  - One-hundred normal, healthy, Yoruba-speaking Nigerian men and women aged 65 and
      above completed the Consortium to establish a Registry for Alzheimer's Disease
      Neuropsychological Battery (CERAD-NB), a cognitive screening battery used in the
      evaluation of elderly patients with suspected dementia. Correlational analyses
      indicated pervasive education-influences on test performance. Gender-effects on
      the CERAD-NB were accounted for by education and there were essentially no age
      effects. Education-stratified normative data are presented for all tests. Factor
      analysis revealed a one factor solution which accounted for 54.7% of the
      variance.

PMID- 7626530
TI  - Contraception: awareness and practice amongst Nigerian tertiary school girls.
AB  - Contraception is analysed in 498 Nigerian Tertiary School Girls--228 from the
      Medical Discipline (MD) of study and 270 from the Non-Medical Discipline (NMD).
      Pregnancy occurred in 30.5% of the sexually exposed students. Overall mean
      awareness of contraception was 70.9% while mean contraceptive usage was 23.5%.
      The most commonly used contraceptive method was the safe-period. Peer group
      constituted the highest source of information on contraception (42.6%) while
      lectures constituted the lowest (11.2%). Sex and contraceptive education
      entrenched into the country's education policy is advocated.

PMID- 7626531
TI  - Pattern of infection of intestinal parasites in Sagbama community of the Niger
      Delta, Nigeria.
AB  - A Parasitology survey was conducted in Sagbama Community of the Niger Delta to
      determine the pattern of infection of intestinal parasites of man. 280 faecal
      samples were collected from randomly selected individuals and examined
      microscopically for ova, larvae and cysts of intestinal parasites. The overall
      infection rate was 33.6%. The frequency of the parasites encountered was as
      follows: Ascaris lumbricoides (18.2%). Entamoeba histolytica (6.4%). Hookworm
      (5.4%). Trichuris trichiura (3.5%), strongyloides stercoralis (3.5%), Schistosoma
      intercalatum (2.5%), Enterobius vermicularis (1.4%), Fasciola hepatic (0.7%) and
      Hymenolepis nana (0.4%). The rate of infection (41.1%) was highest in the 6--15
      years old age bracket and lowest in the age group above 45 years. Prevalence rate
      of the males (37.1%) was statistically different from prevalence rate of the
      females (28.3%) at (P > 0.01). Percentage infection in relation to type of toilet
      facilities showed that the use of "Bush" as convenience carried the highest rate
      of parasitic infection (42.0%) followed by the use of stream/river (36.6%).
      Individuals who used pit, bucket and water closet as toilet facilities had
      infection rates of 27.7%, 20.9% and 15.5% respectively. Rate of infection in
      relation to source of drinking water showed that river/stream, wall/pond and pipe
      borne water had 35.9%, 32.8% and 12.5% respectively. The present study
      demonstrated that the type of toilet facilities and source of drinking water,
      among others, are important determinants of the level of parasitic infection in a
      rural village setting.

PMID- 7626533
TI  - [Problematic management of tumors with a very high proliferation coefficient: a
      case of an embryonal rhabdomyosarcoma of the right orbit in an eleven-year-old
      child].
AB  - We propose through the retrospective analysis of this document, to explain the
      inefficiency of the action of chemo and radiotherapy on tumours with a high
      proliferation coefficient but which are however known to be highly sensitive as
      well as curable with chemo and radiotherapy. This study shows the technical
      conditions and dispositions for a better therapeutic approach in these tumours
      with a rapid growth.

PMID- 7626532
TI  - Surgical treatment of patent ductus arteriosus (PDA). Analysis of 145 cases
      operated on in Abidjan (Cote D'Ivoire).
AB  - This retrospective study aims to analyse our surgical procedures and our results
      after surgery of patent ductus arteriosus (P.D.A.) in children. Since 1978 to
      1992 we have reported Abidjan Cardiology Institute 145 children operated cases.
      The average age was 4.7 years, the average weight 16 kg. There was female
      predominance with a sex ratio of 2.3/1. All patent ductus arteriosus had been
      confirmed by two dimensional echocardiography (2D echocardiography) and cardiac
      catheterization. Type 11a of NADAS' Classification was the most frequent (50%).
      Double or triple ligation supported on teflon felt was the most frequent
      technique used (86 times ie 59.3%). This technique gave good results in view of
      the absence of hospital mortality, only 4 cases of ductus "recanalization"
      supervened, a low rate of ductus arteriosus recurrence patency at long follow up
      of all patients from one to 10 years (mean 5 years). Double or triple ligation on
      teflon felt according to Wright procedure seems to be a securising technique
      alternative in our countries.

PMID- 7626534
TI  - Lung cancer at the University College Hospital, Ibadan, Nigeria.
AB  - A 30-year retrospective review of cases of lung cancer from the Cancer Registry
      of the University College Hospital (UCH), Ibadan Nigeria was carried out. A total
      of 142 cases were analyzed with a male:female ratio of 1.7:1. Peak age incidence
      in females was 2 decades (4th) earlier than for males. Squamous cell carcinoma
      was found most commonly but adenocarcinoma predominated in females.
      Mucoepidermoid and adenoidcystic carcinomas were absent. About 27% of patients
      were under 40 years old and the majority of these (82%) showed the bad prognosis
      histological variants (i.e. anaplastic carcinoma, adenocarcinoma, small cell
      tumours and sarcomas). At autopsy the original lymph nodes were founded to be
      most commonly involved by secondary metastases while the spinal cord was least
      involved. The epidemiology of malignant lung tumours in Ibadan probably differs
      from that in the more industrialized countries and this suggests a different view
      of risk factors for this environment. Additionally there is an urgent need for
      developing methods for earlier diagnosis if the mortality associated with this
      disease is to be reduced especially as it occurs predominantly in young people.

PMID- 7626535
TI  - Jigger infestation in children in a rural area of Rivers State of Nigeria.
AB  - During a survey in April 1991 to determine the immunisation status of 218
      children resident in a rural riverine community, 49 (22.48) were found to have
      been infested with Tunga penetrans. Itching and ulceration were the commonest
      symptoms. The feet were infested in all children, none of whom was taken to a
      health facility. 42.86% of infested children received complete doses of DPT.
      Parents reported no complications of infestation. Tungiasis is an important
      infestation in rural dwellers. The need for adequate childhood immunisation and
      use of protective clothing and shoes are highlighted.

PMID- 7626536
TI  - Hydrocephalus and cerebral palsy due to Acinetobacter meningitis in neonate.
AB  - Earlier reports on acinetobacter infections in neonates described the infections
      as essentially opportunistic and indolent. We described here a case of
      acinetobacter infection in a neonate, which ran a relentless course and resulted
      in hydrocephalus and cerebral palsy. The difficulty encountered in establishing a
      bacteriological diagnosis in the absence of a qualified microbiologist is
      stressed.

PMID- 7626537
TI  - Vesical schistosomiasis at Odau village in Ahoada Local Government Area, Rivers
      State, Nigeria.
AB  - Studies on Urinary schistosomiasis and its snail vector was undertaken between
      October 1991 and September 1992 in Odau. Of the 890 urine specimens examined 514
      (57.8%) were infected. 235 (45.7%) were excreting under 100 eggs per 10ml urine,
      167 (32.5%) were excreting between 100-500 eggs per 10ml urine while 112 (21.7%)
      were excreting more than 500 eggs in 10ml of urine. Of the 514 infected persons
      336 (60.5%) were males and 178 (53.1%) were females. Overall peak infection
      (78.7%) occurred in 10-14 years group. Male infection peaked (83.7%) in the 15-19
      age bracket while peak infection in the females (73.1%) was in 10-14 years age
      group. Two snail vectors, Bulinus globosus and Bulinus forskalii, were collected
      from the study area. Bulinus forskalii was not infected with cercarise of
      schistosome throughout the study period. B globosus was found infected with
      furcereus cercariae believed to be human schistosomes. Population trend of
      Bulinus globosus was closely studied and observed to be related to infection with
      schistosome cercaria. Two broad transmission foci were located. One was in the
      village ponds where more children were infected. The other was in the pits,
      ditches and swamps in the plantations where the adults were infected. Control of
      schistosome infection through chemotherapy will best be achieved by January
      because immediate reinfection of parasites is not possible owing to the drying
      out of the ponds in January and February. And control of the snail vectors will
      be best in March and April because a large proportion of snail population is
      young and highly vulnerable to molluscicide attacks.

PMID- 7626538
TI  - Straight-back syndrome. A case report and review of the literature.
AB  - This is a case report of an unusual clinical entity-the Straight Back Syndrome
      (SBS), in a two and a half (2 1/2) year old cerebral palsied Ghanalan male child.
      It was an incidental finding in which his lateral x-ray of the chest revealed a
      straight thoracic spine, devoid of the normal thoracic concavity. Organic heart
      disease was excluded by his normal electrocardiogram (EGG) and echocardiogram.
      Review of the literature shows that whereas in the sixties, this syndrome bore no
      associations with structural heart diseases, in the nineties, there have been
      significant organic heart defects described as its associates. The reports are
      however, silent on any association between cerebral palsy and the straight back
      syndrome.

PMID- 7626539
TI  - Calcified pleuropericardic cysts--2 cases report.
AB  - Pleuropericardic cysts represent 5 to 7 per cent of tumours of the mediastinum.
      Their origin is a defect in development of pericardic coelomic cavities. They are
      located in the right and cardio-phrenic corner in 70 per cent of cases. They are
      generally asymptomatic. They are best treated by a thin needle puncture under
      scanography. Surgery is needed only when the cyst wall is thick. We have treated
      surgically 2 cases of large cysts, because of their sizes (10 cm and 13 cm of
      diametres respectively), and, mostly, because of their calcification.
      Symptomatology was dominated by respiratory signs, such as dyspnea. In one case,
      there were manifestations of inferior vena cava compression. Diagnosis was done
      by roentgenography of the thorax. The surgical procedure, using right
      thoracotomy, revealed a calcified cyst in both cases, with a tough wall, which
      was resected. In one case, the removal of adhesion to the inferior vena cava
      injured this vessel which was sutured after partial clamping. Hemorrhage was
      severe and 2.51 blood transfusion was necessary. The post operative course was
      uneventful. Clinical signs of compression disappeared in both cases.

PMID- 7626540
TI  - Prevalence of urinary tract infection among school children in a Nigerian rural
      community.

PMID- 7626541
TI  - Empirical aspects of symmetry perception.

PMID- 7626542
TI  - Evidence for the use of scene-based frames of reference in two-dimensional shape
      recognition.
AB  - A series of reaction time (RT) experiments are reported in which subjects had to
      match pairs of two-dimensional shapes. The shapes were either symmetrical or
      asymmetrical and were arranged into either symmetrical or asymmetrical displays.
      In the initial experiments the shapes straddled the vertical midline of the
      display. It was found that Same RTs to symmetrical displays were shorter than
      Same RTs to asymmetrical displays, and that Same RTs to symmetrical shapes were
      shorter than Same RTs to asymmetrical shapes. Moreover, display symmetry and
      shape symmetry produced an additive effect on responses. This pattern of results
      obtained when both shapes were presented simultaneously and when a delay was
      introduced between the presentation of one shape and the presentation of the
      other. However, display and shape symmetry interacted when the displays were
      rotated 90 deg within the plane so that the shapes straddled the horizontal
      meridian. The implications of these results are discussed in terms of both a
      transformational account of shape recognition and an account concerning the
      imposition and use of scene-based frames of reference.

PMID- 7626543
TI  - Independence of bilateral symmetry detection from a gravitational reference
      frame.
AB  - Data were collected during three orbital flights aboard the Russian MIR space
      station from eight cosmonauts tested on a bilateral symmetry detection task. It
      is known that on earth subjects' performance is significantly superior for a
      vertical or horizontal than for an obliquely oriented axis of symmetry, giving a
      so-called oblique effect. The present results show that this oblique effect did
      not disappear in microgravity. They confirm that the detection of visual symmetry
      is not tied to a gravitational reference frame. An unexpected result of the
      experiments was that practice reduced the reaction time for detection of
      asymmetrical patterns below that for symmetrical patterns. This result suggests
      the presence of two separate detection processes. The detection of symmetry,
      being useful for the efficient encoding of visual information, is well developed
      in naive subjects. Extensive practice on a symmetry-detection task, however,
      increases the efficacy of the asymmetry-detection process.

PMID- 7626544
TI  - Level of processing in the perception of symmetrical forms viewed from different
      angles.
AB  - This study is concerned with the level of processing underlying the perception of
      symmetry about a vertical axis. Specifically, it asks whether the equality of the
      two sides of a symmetrical pattern must be present retinally or perceptually for
      the impression of symmetry to be realized. Sixty-four subjects were assigned to
      groups that viewed symmetrical and asymmetrical figures when the figures were in
      either a frontoparallel plane or one slanted by 65 deg from the line of sight. In
      the 65 deg condition, the objectively symmetrical stimuli projected an
      asymmetrical shape on the retina, and conversely the objectively asymmetrical
      stimuli produced a symmetrical retinal projection. From each viewing angle,
      patterns were observed under either full or reduced (monocular) depth cue
      conditions. Like their counterparts in the frontoparallel condition, observers in
      the 65 deg, full depth-cue condition identified the objective symmetry of the
      figures. By contrast, 65 deg, reduced depth-cue observers responded primarily to
      the retinal structure of the stimuli. The same pattern of responding was observed
      for both holistic and multielement patterns and for both 100 ms and 1 s
      exposures. These findings and the significant relationship obtained between
      phenomenal judgment of symmetry and a measure of shape constancy suggest that the
      perception of symmetrical figures depends upon the perception of the equality of
      their two halves, and is thus another example of perceptual causality.

PMID- 7626545
TI  - Human discrimination of surface slant in fractal and related textured images.
AB  - Slant-discrimination thresholds were measured for textures with the property that
      their power spectra, when log transformed, are inversely proportional to log
      spatial frequency: P(f) alpha f-beta. As the exponent beta changes from high
      values to low values, the slope of the power spectrum of the image decreases. As
      the parameter passes through values in the fractal range the resulting texture
      changes from having the appearance of a cloud-like surface through to a granite
      like surface. Exponents below the fractal range produce textures that converge
      towards the appearance of a random grey-level noise pattern. Since fractal
      patterns are self-similar at a range of scales, one might think it would be
      difficult to recover changes in depth in fractal images; however, slant
      discrimination thresholds did not differ substantially as a function of the slope
      of the power spectrum. Reducing the size of the viewing aperture increased
      thresholds significantly, suggesting that slant discrimination benefits from a
      global analysis. The effect of texture regularity on perceived slant was
      investigated using bandpassed fractal textures. As the bandwidth of a bandpass
      filter is reduced, the bandpassed texture was perceived to be increasingly more
      slanted than its fractal counterpart.

PMID- 7626546
TI  - A model for global symmetry detection in dense images.
AB  - In this paper, a model is proposed for bilateral symmetry detection in images
      consisting of dense arrangements of local features. The model is elaborated on
      the basis of a psychophysical experiment showing that grouping precedes and
      facilitates symmetry detection. The proposed computational model consists of
      three stages: a grouping stage, a symmetry-detection stage, and a symmetry
      subsumption stage. Reliance upon a preliminary grouping stage enables a
      significant reduction of the computational load for detecting symmetry. An
      implementation of the model is described, and results are presented, showing a
      good agreement of the model performance with human symmetry perception.

PMID- 7626547
TI  - The role of pattern outline in bilateral symmetry detection with briefly flashed
      dot patterns.
AB  - Experiment 1 demonstrates that, while the outline shapes of bilaterally
      symmetrical dot patterns play a role in symmetry detection, the removal of the
      outline by a surrounding random-dot annulus merely reduces performance by a fixed
      amount. It does not affect the relative salience of different symmetry-axis
      orientations. The converse is also true: performance is almost as good when the
      symmetrical dot pattern is confined to the surrounding annulus but is disrupted
      similarly when the central area is filled with random dots (Experiment 2). In
      Experiment 3, any one or more of three areas--a central circular area and two
      surrounding annuli--could be filled with vertically symmetrical or random dots
      and symmetry was detected reliably only when the central circular area contained
      the symmetrical dots. A new paradigm was explored in Experiment 4: subjects
      judged the orientation--left or right of vertical--of 20-dot symmetrical patterns
      oriented 1-4 deg left or right of vertical and with or without surrounding random
      outline masks. Surprisingly, the orientation judgments were extremely precise,
      with JNDs of the order of 1 deg or less, and outline masking dots made no
      difference. Experiment 5 showed that performance was even better with just two
      dots and it made no difference whether these were separated by just under 4 deg
      or just over 20 deg. It was concluded that while pattern outline plays some role
      in dot symmetry detection, the major mechanisms are located near the fovea. It is
      suggested that the relative salience of vertical and horizontal symmetry only in
      central vision is related to the preponderance of foveal cells tuned to those
      orientations (Mansfield, Science 186, 1133-1135, 1974; Mansfield and Ronner,
      Brain Res. 149, 229-234, 1978) but that attentional factors and scanning
      strategies also boost the salience of oblique symmetry and the salience of
      vertical over horizontal symmetry (Wenderoth, Perception 23, 221-236, 1994).

PMID- 7626548
TI  - Multiple mechanisms for the detection of mirror symmetry.
AB  - Symmetry detection was investigated for static and dynamic noise targets
      consisting of a field of approximately 0.3 million random dots on which was
      imposed a bilateral symmetry. The minimum duration for detection was 40 ms for
      static and 80 ms for dynamic symmetry. The exponents of the psychometric
      functions averaged about 4 for both static and dynamic tasks, as opposed to the
      value of 1 expected for such suprathreshold tasks, implying that there is some
      neural mechanism performing full temporal integration of the symmetry information
      up to durations of a second or more. Static symmetry was perceivable when
      information around the symmetry axis was masked up to 3 deg away from the
      symmetry axis, revealing extrafoveal symmetry detection in approximately 300 ms
      exposures. The static data were fitted with a model consisting of three
      mechanisms with Gaussian spatial profiles and mutual inhibition (two mechanisms
      were sufficient for the dynamic data). The profile of the widest mechanism was 20
      times wider for static than for dynamic symmetry.

PMID- 7626549
TI  - Detection of visual symmetries.
AB  - This paper reviews empirical evidence for the detection of visual symmetries and
      explanatory theories and models of symmetry detection. First, mirror symmetry is
      compared to other types of symmetry. The idea that symmetry detection is
      preattentive is then discussed and other roles that attention might play in
      symmetry detection are considered. The major part of the article consists of a
      critical examination of the extensive literature about the effects on symmetry
      detection of several major factors such as the orientation of the symmetry axis,
      the location of the stimulus in the visual field, grouping, and perturbations.
      Constraints on plausible models of symmetry detection are derived from this rich
      database and several proposals are evaluated against it. As a result of bringing
      this research together, open questions and remaining gaps to be filled by future
      research are identified.

PMID- 7626550
TI  - Relationships among 64k autoantibodies, pancreatic beta-cell function, HLA-DR
      antigens and HLA-DQ genes in patients with insulin-dependent diabetes mellitus in
      Korea.
AB  - OBJECTIVES: Among autoantibodies detected in patients with insulin-dependent
      diabetes mellitus (IDDM), antibodies to 64,000(Mr) islet protein(64k), now
      recognized as glutamic acid decarboxylase(GAD), appear to be an even more
      predictive marker of IDDM than islet cytoplasmic antibody (ICA) or insulin
      autoantibody (IAA). We examined the relationships among 64k autoantibodies,
      pancreatic beta-cell function, HLA-DR antigens and HLA-DQ genes in patients with
      IDDM in Korea. METHODS: To identify the 64k autoantibody, the immunoprecipitation
      method was performed for 35 patients with IDDM and 10 normal controls. In
      patients with IDDM, serum C-peptide levels were measured and HLA-DR typings and
      HLA-DQA1 and DQB1 gene typings were performed. RESULTS: 12 of 35 (34%) patients
      with IDDM were positive for 64k autoantibody in contrast to none of 10(0%) normal
      controls. There were no differences in residual pancreatic beta-cell function
      between 64k autoantibody positive and negative groups. 64k autoantibody was
      detected more frequently in patients with recent (duration < 6 months,
      10/25[40%]) and young -aged(aged < 15 years, 7/18[39%]) onset of IDDM. All of
      3(100%) patients with HLA-DR3/DR4 heterotypes were positive in 64k autoantibody,
      in contrast to 1 of 7(14%) patients without HLA-DR3 nor DR4. The frequencies of
      HLA-DQA1*0301, HLA-DQB1*0201, DQB1* 0302 and DQB1*0303 gene types were higher in
      patients with 64k autoantibody (12/12 [100%]) vs. without 64k autoantibody
      18/22[81%], 5/11[45%] vs. without 64k autoantibody 5/22[23%], 5/11[45%] vs.
      without 64k autoantibody 8/22[36%] and 6/11 [55%] vs. without 64k autoantibody
      9/22[41%]. CONCLUSIONS: There results suggest that 64k autoantibodies have some
      relationship with HLA-DR, DQA1 and DQB1 genes, but not with residual pancreatic
      beta-cell function in Korean patients with IDDM.

PMID- 7626551
TI  - Circulating intercellular adhesion molecule-1(ICAM-1) in sera of patients with
      Graves' disease and Hashimoto disease.
AB  - OBJECTIVES: Intercellular adhesion molecule-1 (ICAM-1), a 80-110 kD glycoprotein,
      has been found to be a ligand for the lymphocyte function associated antigen-1
      (LFA-1) molecule and has important roles in inflammatory and immune mediated
      mechanisms. ICAM-1 is expressed on thyroid follicular cells of patients with
      Hashimoto disease and cultured thyroid monolayer cells derived from the thyroid
      surgical specimen. In addition to the expression of ICAM-1 on the surface of
      cells, soluble variants of several adhesion molecules have been reported.
      METHODS: We evaluated the circulating ICAM-1 in sera of representative autoimmune
      thyroid disease, Hashimoto and Graves' disease, and analyzed correlations between
      circulating ICAM-1 and thyroid-directed autoantibodies. Sera were collected from
      58 patients with autoimmune thyroid disease, 28 patients with Graves' disease and
      30 patients with Hashimoto disease. Serum concentrations for circulating ICAM-1
      were determined with sandwitch enzyme immunoassay. RESULTS: Compared with normal
      individuals, mean serum concentrations for circulating ICAM-1 were significantly
      elevated in patients with Hashimoto disease and antithyroperoxidase-positive
      Graves' disease. Patients with antithyroperoxidase-positive Graves' disease
      revealed significantly higher serum circulating ICAM-1 concentrations than
      antithyroperoxidase-negative Graves' disease. Circulating ICAM-1 showed
      significant positive correlation with serum titers of antithyroglobulin and
      antithyroperoxidase antibody (r = 0.44, n = 28, p = 0.009, and r = 0.55, n = 28,
      p = 0.001 respectively). There was a significant positive correlation between
      circulating ICAM-1 levels and serum antithyroperoxidase level in the group of
      autoimmune thyroid disease and also circulating ICAM-1 levels were significantly
      correlated with serum antithyroperoxidase antibody levels in antithyroperoxidase
      antibody-positive Graves' disease(r = 0.55, n = 28, p = 0.001) and in Hashimoto
      disease (r = 0.5, n = 30, p = 0.002). The thyrotropin binding inhibiting
      immunoglobulins(TBII) showed no significant correlation with circulating ICAM-1
      levels. CONCLUSIONS: In the present study, high serum levels of ICAM-1 were
      associated with autoimmune thyroid disease. Graves' disease and Hashimoto disease
      and positively correlates with levels of antithyroperoxidase antibody.

PMID- 7626552
TI  - Neutrophil chemotactic activities in bronchoalveolar lavage fluid from patients
      with bronchial asthma.
AB  - OBJECTIVES: To elucidate the presence of neutrophil chemotactic factor (NCF) and
      characterize them in the bronchial trees of symptomatic patients with bronchial
      asthma. METHODS: Bronchoalveolar lavage (BAL) fluids were concentrated by
      ultrafiltration. Differential counts of BAL cells was performed upto 500 cells on
      the cytocentrifuge-prepared slides. NCF activities in concentrated BAL fluids
      were measured by using microchemotactic chamber. These NCF activities were
      characterized by heat-stability, sensitivity to trysin and solubility into
      organic solvent. RESULTS: NCF activities were significantly higher in low
      molecular weight (LMW)-BAL fluid fraction below 5000 dalton than those in high
      molecular weight (HMW)-BAL fluid fraction. The NCF activities were significantly
      higher in the patients with bronchial asthma when compared to those of normal
      subjects. The LMW-NCF and HMW-NCF activities were correlated with the percentages
      of neutrophils in BAL fluid in the patients with bronchial asthma. The LMW-NCF
      activities were extractable into ether, stable to heat and resistant to trypsin.
      CONCLUSIONS: Main NCF activities in BAL fluid are suggested to be lipid
      substances with low molecular weight less than 5000 dalton and these substances
      may recruit neutrophils into the bronchial trees of patients with bronchial
      asthma.

PMID- 7626553
TI  - Immune suppression therapy in aplastic anemia: influencing factors on response
      and survival.
AB  - OBJECTIVES: Immune suppression (IS) therapy has provided another opportunity of
      cure or improvement in the aplastic anemia patients who cannot receive bone
      marrow transplantation due to many causes. There are a few reports regarding the
      factors that affect response, survival and prognosis after IS therapy, including
      antilymphocyte globulin (ALG) in aplastic anemia. Therefore, we analysed our
      experience to determine the prognostic factors. METHODS: Statistically analysed
      were 172 patients, from April 1982 to July 1992, who were diagnosed as severe
      aplastic anemia and treated with IS therapy, including ALG, at Catholic
      University Medical College, St. Mary's Hospital. RESULTS: Among 172 severe
      aplastic anemia (SAA) patients who entered the study from April 1982 to July
      1992, 144 patients were analysed for response and 122 patient for survival. 58.4%
      (84/144) responded after the first course of IS therapy. Among those who did not
      respond on the first course an additional 44% (11/25) responded after the second
      course of IS therapy. Prognostic factors that might affect the response to the
      treatment and survival were analysed. In a univariate analysis of patients with
      no previous history of treatment before is therapy, and a shorter interval
      between diagnosis and treatment, higher hemoglobin levels before IS therapy, and
      higher granulocyte counts and combined use use of cyclosporin A(CSA) were
      positively associated with response (p < 0.05). The combined use of CSA during IS
      therapy, younger age, lower monthly requirement of platelets transfusion before
      IS therapy, higher leukocyte counts, higher percent of polymorphonuclear
      leukocytes, lower percent of lymphocyte, higher bone marrow cellularity and
      response were positively associated with survival (p < 0.05). In a multivariate
      analysis, shorter interval between diagnosis and treatment, no combined use of
      hemopoietic stimulants, such as androgen, and lesser total amount of transfusion
      were positively associated with Response (p < 0.05). Higher leukocyte counts
      before IS therapy and the combined use of CSA during IS therapy were
      significantly associated with longer survival (p < 0.05). Patients with complete
      or partial response had excellent prognosis (96.7%-100% of 5 year survival
      rates). In contrast, patients with no response after IS therapy had 45.1% of 5
      year survival rates. CONCLUSIONS: With these results from the retrospective study
      of IS therapy, we find many valuable factors that have an influence on response
      or survival. IS therapy improves the survival of responded patients with SAA, and
      we confirmed that IS therapy is an important therapeutic tool for the SAA
      patients who are not feasible candidates for bone marrow transplantation.

PMID- 7626555
TI  - The incidence of drug resistant tuberculosis in 1279 Korean patients.
AB  - OBJECTIVES: In the past decade, the incidence of tuberculosis has been decreased
      in Korea and the nationwide survey of tuberculosis from 1965 through 1990
      suggested a declining tendency of resistant organisms. But the prevalence rate of
      multidrug resistance of Mycobacterium tuberculosis is still a serious problem in
      Korea, and the aim of this study is to check the drug resistance pattern in the
      patients visiting University Hospital, the 3rd referral center. METHODS: We
      reviewed 1279 cases (522 female, 757 male, mean age 39.4 +/- 16.7) of
      bacteriologically proven tuberculosis seen during the period from 1986 to 1992
      retrospectively. Of 1093 patients, who were indentified in previous medical
      history, 454 (41.5%) had a history of prior antituberculous chemotherapy.
      RESULTS: Resistance rate (resistant to 1 or more drugs) was 33.9%. Eleven percent
      of patients had resistance to a single drug (INH: 80.6%). Twenty two percent of
      patients had resistance to 2 or more drugs. Resistance rate is higher (47.4%) in
      the patients with a history of prior treatment than without a history (25.5%).
      CONCLUSIONS: These data suggest that the high rate of multidrug resistance in
      Korea did not show any decreasing tendency. So, mycobacterial culture and
      sensitivity tests should be recommended at initial treatment of tuberculosis and
      potent antituberculosis drugs are strongly recommended.

PMID- 7626554
TI  - Combination chemotherapy with cyclophosphamide, vincristine, cisplatin and
      etoposide (COPE) combined with radiotherapy for small cell lung cancer.
AB  - OBJECTIVES: Small cell lung cancer is sensitive to chemotherapy and radiotherapy.
      Nevertheless, responses are still short-lived and apparent cure remains for only
      limited disease patients. METHODS: We combined cyclophosphamide (750 mg/m2 by
      intravenous infusion at first day) vincristine (2 mg intravenously at third day),
      cisplatin (20 mg/m2 intravenously for 3 days), and etoposide (100 mg/m2
      intravenously for 3 days) with radiotherapy (total 300cGy over 4 weeks in 17
      fractions) and treated 39 patients with small cell lung cancer who had received
      no prior systemic chemotherapy and radiotherapy. RESULTS: 1) Thirty-nine patients
      (limited disease: 17 patients, extensive disease 22 patients) were treated and 35
      patients were evaluable for response. Overall response rate was 82.8% (complete
      response 28.6%, partial response 54.2%). 2) The median survival was 52 weeks for
      all patients and 58 weeks for limited disease and 45 weeks for extensive disease.
      There was no statically significant survival difference between the two patient
      groups. The median relapse-free survival time was 48 weeks. 3) Overall, treatment
      was well tolerated, with granulocytopenia being the most frequent toxicity.
      CONCLUSIONS: Combination chemotherapy with COPE regimen combined with radiation
      therapy was effective as a first line therapy for SCLC.

PMID- 7626556
TI  - Tc-99m dimercaptosuccinic acid(DMSA) renal scintigraphy in patients with acute
      pyelonephritis.
AB  - OBJECTIVES: Recently, several authors reported that Tc-99m DMSA renal scan
      frequently showed cortical defects of the involved kidneys even in the patients
      with acute pyelonephritis who did not show abnormal findings in the
      ultrasonography and intravenous pyelography (IVP). METHODS: In order to evaluate
      the utilities of Tc-99m DMSA renal scan and the clinical meaning of cortical
      defects in the Tc-99m DMSA renal scan of the patients with acute pyelonephritis,
      ninety two patients with acute pyelonephritis, from March 1991 to February 1994
      in Chungnam National University Hospital(CNUH), were included in this study.
      Patients were subdivided as Group A:Patients showing normal Tc-99m DMSA renal
      scan (n = 42) and Group B:Patients with definite cortical defects on the Tc-99m
      DMSA renal scan (n = 50). We compared clinical characteristics such as age and
      sex, recurrency, duration of fever, bacterial culture study, incidence of renal
      insufficiency and the results of renal ultrasonography and intravenous
      pyelography between the two groups. RESULTS: Fifty four percents of 92 patients
      with acute pyelonephritis showed a significantly longer febrile period after
      admission, higher positive rates on the urine and blood culture studies and
      higher incidence of renal insufficiency than those of the Group A patients. Sixty
      nine percents of Group B patients showed normal results in ultrasonography or IVP
      study. CONCLUSIONS: Tc-99m DMSA renal scan was a more sensitive imaging test than
      ultrasonography in kidneys and IVP to detect pyelonephritis lesions and may be
      useful to predict the patient group with a severe disease course. These patients
      may need more careful management and further studies to evaluate the possibility
      of complications.

PMID- 7626557
TI  - Renal function and hemodynamic study in obese Zucker rats.
AB  - OBJECTIVES: To investigate the renal function and hemodynamic changes in obesity
      and hyperinsulinemia which are characteristics of type II diabetes. METHODS:
      Studies were carried out in two groups of female Zucker rats. Group 1 rats were
      obese Zucker rats with hereditary insulin resistance. Group 2 rats were lean
      Zucker rats and served as controls. In comparison with lean Zucker rats, obese
      Zucker rats exhibited hyperinsulinemia but normoglycemia. Micropuncture studies
      and morphologic studies were performed in these rats. RESULTS: Functional studies
      showed that obese Zucker rats exhibited increases in kidney weight and GFR(obese
      Zucker, 1.23 +/- .07)ml/min; lean Zucker, 0.93 +/- .03ml/min). Micropuncture
      studies revealed that the increase in GFR in obese Zucker rats was attributable
      to the increases in the single nephron plasma flow rate and glomerular
      transcapillary hydraulic pressure. The glomerular ultrafiltration coefficient was
      the same in both groups. Morphologic studies revealed that the increase in GFR in
      obese Zucker rats was associated with an increase in glomerular volume.
      CONCLUSIONS: These results suggest that obesity and hyperinsulinemia, which are
      the characteristics of type II diabetes, can be associated with glomerular
      hyperfiltration and glomerular capillary hypertension.

PMID- 7626558
TI  - A case of Henoch-Schonlein purpura in disseminated tuberculosis.
AB  - Tuberculosis is still a common disease, even in some parts of developing
      countries. Although its major impact is pulmonary, the tuberculosis is actually a
      disseminated disease. An unusual form of renal involvement of tuberculosis is
      glomerulonephritis, as a part of systemic vasculitis, Henoch-Schoenlein Purpura
      (HSP). A 41-year-old man, being treated with antituberculous agents for pulmonary
      tuberculosis, was transferred to our hospital because of newly developed
      generalized purpura and pretibial edema. Renal manifestations were proteinuria
      and hematuria. Renal biopsy disclosed interstitial chronic granulomatous
      inflammation with caseous necrosis and strong nodular mesangial Ig A deposit,
      along with trace granular Ig G deposition and perivascular C3 deposit. Skin
      lesions were non-thrombocytopenic palpable purpurae, proved leukocytoclastic
      vasculitis by skin biopsy. All clinical symptoms and signs were relieved by
      antituberculous medication. We concluded that disseminated tuberculosis might be
      a cause of HSP, an immune complex mediated disease.

PMID- 7626559
TI  - A case of adult-onset Bartter's syndrome.
AB  - Bartter's Syndrome is characterized by renal potassium wasting with hypokalemia,
      metabolic alkalosis, increased renin-angiotensin-aldosterone system, normal blood
      pressure, resistance to the pressor effects of angiotensin II and juxtaglomerular
      cell hyperplasia. Most of the cases have been noted in the pediatric age group
      and adult-onset cases are very rare. We report a case of adult-onset Bartter's
      syndrome.

PMID- 7626560
TI  - Cushing's syndrome due to primary pigmented nodular adrenocortical disease--a
      case report reviews of the literature.
AB  - Primary pigmented nodular adrenocortical disease (PPNAD) is a rare cause of
      Cushing's syndrome in infants, children and young adults. It is characterized by
      non-adrenocorticotropic hormone-dependent hypersecretion of cortisol by multiple,
      pigmented nodules of hyperplastic adrenocortical cells. Biochemically, PPNAD is
      characterized by elevated levels of plasma and urinary cortisol that are not
      suppressed by high doses of dexamethasone (8mg/d for 2 days). Pathologically, the
      adrenal glands contain multiple dark brown or black nodules and the intervening
      cortical tissue is atrophic. Recognition of this diagnosis, although rare, is
      important, as bilateral adrenalectomy is the treatment of choice. We experienced
      a case of Cushing's syndrome due to primary pigmented nodular adrenocortical
      disease and report it with reviews of the literature.

PMID- 7626561
TI  - A case of huge solitary angiomyolipoma of the liver.
AB  - A 32-year-old male patient, diagnosed as a hepatic solitary angiomyolipoma post
      operatively, is reported. The tumor was well definedly inhomogenous fat density
      mass on ultrasonography, computerized tomography (CT) and magnetic resonance
      imaging (MRI). The lesion was hypervascular on arteriography. The diagnosis was
      confirmed by an extended right lobectomy and histological examination.

PMID- 7626562
TI  - Macular holes.

PMID- 7626563
TI  - Uveal melanoma: cell cycles and survival.

PMID- 7626564
TI  - Ophthalmic services research: towards increasing the role of economic and
      operations research methods in the delivery of eye care services.

PMID- 7626565
TI  - Natural outcomes of stage 1, 2, 3, and 4 idiopathic macular holes.
AB  - AIMS: A study was carried out to ascertain the natural outcome of each stage of
      idiopathic macular hole. METHODS: One hundred and fifty four eyes with different
      stages of idiopathic macular holes were retrospectively studied: stage 1 (40
      eyes), 2 (25 eyes), 3 (58 eyes), and 4 (31 eyes). RESULTS: Of 27 of 40 eyes with
      a stage 1 lesion with posterior vitreous attachment to the macula initially, nine
      (33%) eyes developed a full thickness macular hole. No stage 1 lesions with
      posterior vitreous separation from the macula initially progressed to full
      thickness holes. Twenty one (84%) of 25 eyes with a stage 2 lesion, 32 (55%) of
      58 eyes with a stage 3 lesion, and five (16%) of 31 eyes with a stage 4 lesion
      underwent macular hole enlargement during the median follow up period of 3 years.
      Visual acuity decreased two or more lines of Snellen equivalent during the follow
      up period in 12 (30%) eyes with a stage 1 lesion, 17 (68%) eyes with a stage 2
      lesion, 17 (29%) eyes with a stage 3 lesion, and four (13%) eyes with a stage 4
      lesion. The percentage was significantly higher in eyes with stage 2 lesions than
      the other stages (p < 0.01). CONCLUSION: The results suggest that the different
      stages of idiopathic macular holes have different natural outcomes, and the
      management depends on the stage at presentation.

PMID- 7626566
TI  - DNA index and S phase fraction in uveal malignant melanomas.
AB  - AIMS: To predict 5 year survival in patients with uveal malignant melanomas DNA
      indices were studied. METHODS: Using 45 paraffin embedded uveal malignant
      melanomas, the DNA index and S phase fraction of each tumour were the predictor
      variables recorded. RESULTS: Using the Cox proportional hazards model, aneuploid
      tumours and tumours which had an S phase fraction greater than 4% were
      significant predictors of early death. In order to demonstrate a biological
      gradient between a larger DNA index and shorter survival time, linear regression
      and transformed linear regression models were used. However, no such gradient
      could be demonstrated. CONCLUSION: Although this study shows promise for the use
      of DNA studies in the prognosis of uveal malignant melanoma, the exact role of
      these techniques remains to be determined.

PMID- 7626567
TI  - Study of nuclear cataract progression using the National Eye Institute
      Scheimpflug system.
AB  - AIMS: A study was conducted to determine the capability of the recently developed
      National Eye Institute (NEI) Scheimpflug cataract imaging system in detecting
      changes in the nuclear region of the lens over a 1 year period. METHODS: Twenty
      five eyes with pure nuclear cataracts with mean nuclear densities < or = 0.30
      optical density units (ODU) as well as 30 normal control eyes were each examined
      at baseline and 12 months later. Computerised densitometry using the NEI
      Scheimpflug cataract imaging system was performed. Clinical grading of the lenses
      was also done using the Lens Opacities Classification System II (LOCS II). For
      densitometry, a change of plus or minus 0.023 ODU (the 99% range) in mean density
      in the nuclear area was considered a progression or regression at 1 year.
      RESULTS: Using the Scheimpflug densitometry, 14 of the 25 cataractous eyes showed
      significant progression at 1 year. In the normal control group, only three of the
      30 eyes showed significant progression. In contrast, using the LOCS II clinical
      grading, only two of the 25 cataractous eyes showed a one step increase, two of
      the 30 controls progressed at 1 year, and none regressed. There was no
      significant difference in visual acuity. CONCLUSION: This study suggests the
      value of the NEI Scheimpflug cataract imaging system in detecting nuclear change
      within 1 year. However, clinically significant changes may require longer follow
      up periods. These data will be useful in planning future longitudinal studies of
      nuclear cataracts, such as for clinical trials of anticataract drugs.

PMID- 7626568
TI  - Longitudinal study of posterior subcapsular opacities using the National Eye
      Institute computer planimetry system.
AB  - BACKGROUND: The National Eye Institute (NEI) computer planimetry system has
      proved to be helpful in cross sectional studies by providing clinically useful
      area measurements of posterior subcapsular cataracts (PSC) and other opacities
      from retroillumination photographs. In this study, we evaluated the worth of this
      system in detecting PSC area changes over time. METHODS: Using the Neitz-Kawara
      camera, retroillumination photographs of the PSCs of 51 eyes were obtained every
      6 months for an average of 25 months. The PSCs were outlined in a masked fashion
      on plastic overlays. Their tracings were then digitised on to a computer using a
      scanner. PSC area was determined using a special software program. For each eye,
      the rate of PSC area change was estimated by the slope of the regression line
      fitted to the follow up measurements. Cataract progression was classified as
      significant if the slope exceeded a critical value. RESULTS: These showed that 14
      of the 51 eyes had PSC progression, while 37 did not change. CONCLUSION: This
      study suggests the system is useful for longitudinally monitoring PSC area
      changes from retroillumination photographs. This system would serve in natural
      history studies of PSCs and in clinical trials of anticataract drugs. The slope
      based test can play a part in longitudinal studies with irregular time intervals
      and variable number of visits.

PMID- 7626569
TI  - Pupil size and reactivity following hydroxypropyl methylcellulose and sodium
      hyaluronate.
AB  - AIMS: A prospective randomised clinical trial was set up to compare the effect of
      hydroxypropyl methylcellulose (Ocucoat) and sodium hyaluronate (Healonid) on
      pupil size and reactivity following their use in cataract surgery. METHODS: Pupil
      measurements were recorded before and 6 weeks after surgery. RESULTS: There was
      no significant difference between the two groups with respect to pupil size (p =
      0.69, Mann-Whitney U test) nor with respect to reactivity (p = 0.99, Fischer's
      exact test). Ninety six per cent of the surgery was performed using
      phacoemulsification. CONCLUSION: This trial suggests that both viscoelastic
      materials have similar effects on the pupil after their use in cataract surgery.

PMID- 7626570
TI  - Comparison of the effects on pupil size and accommodation of three regimens of
      topical dapiprazole.
AB  - BACKGROUND: Patients who have their pupils dilated for an eye examination
      traditionally have to wait several hours before their pupils return to normal
      size and their blurred vision (caused by paralysis of accommodation) resolves.
      Earlier studies with dapiprazole have demonstrated an accelerated reversal of
      dilatation. METHODS: Three regimens of dapiprazole were studied to determine the
      effects on pupil diameter and accommodation after mydriasis produced by 2.5%
      phenylephrine and 0.5% tropicamide. Test regimens included one drop and 1 + 1
      drop regimens, compared with a 2 + 2 drop reference regimen. Dapiprazole was
      administered in one eye and placebo in the other. Mean change from baseline was
      analysed for pupil diameter and accommodation at various time points after drug
      administration. Also, for the same variables, 90% confidence intervals for the
      areas under the curve (AUC) were computed. RESULTS: Both test regimens were
      equivalent to the reference regimen on the basis of mean change from baseline for
      pupil diameter and accommodation at individual time points, and for the mean AUC.
      Most signs and symptoms (injection, stinging, burning, lid oedema, and ptosis)
      were less frequent in the test regimen treated eyes. There was no significant
      interaction between regimen and eye colour. CONCLUSION: This study indicates that
      a lower dosage (for example, one drop) is also efficacious and has the added
      benefit of fewer side effects.

PMID- 7626571
TI  - Inflammation after cataract extraction and intraocular lens implantation in
      patients with rheumatoid arthritis.
AB  - AIMS: The purpose of this study was to examine whether preoperative activity of
      rheumatoid arthritis influences the extent of anterior chamber inflammation after
      cataract extraction and intraocular lens implantation. METHODS: The medical
      records of 23 consecutive patients (33 eyes) with rheumatoid arthritis, who
      underwent cataract extraction with intraocular lens implantation, were reviewed
      during a 4 year period from April 1990 to March 1994. RESULTS: Eleven patients
      who still showed a 1+ level of aqueous cells 1 month after the surgery had
      significantly higher titres of rheumatoid factor preoperatively, compared with
      the other 12 patients who showed no aqueous cells (p = 0.0019, Mann-Whitney U
      test). The persistence of aqueous cells also had a significant correlation with
      extracapsular cataract extraction compared with phacoemulsification (p = 0.0391,
      chi 2 test). Multivariate analysis showed that the titre of rheumatoid factor was
      the more significant element to determine the persistent aqueous inflammation.
      All the eyes, except for four which had a macular hole, optic disc atrophy, or
      retinitis pigmentosa gained visual acuity of 20/30 or better. The aqueous cells
      cleared 3 months after the surgery and left no complications in any of the eyes.
      CONCLUSION: Intraocular lens implantation is basically a safe procedure for
      patients with rheumatoid arthritis, although postoperative aqueous inflammation
      tends to be persistent in patients with high titres of rheumatoid factor.

PMID- 7626572
TI  - Reproducibility with the Keeler Pulsair 2000 non-contact tonometer.
AB  - AIMS: The IOP variation on repeated testing with the recently introduced Keeler
      Pulsair 2000 instrument was investigated. METHODS: One hundred normal individuals
      (50 male and 50 female) new to the instrument had three sets of IOP recordings
      within a 15 minute time period. RESULTS: The mean of the first set of IOPs from
      both right and left eyes was significantly higher than those from subsequent sets
      (p < 0.0001 for right eyes and p = 0.01 and < 0.0002 for left eyes). This
      tendency increased significantly with increasing IOP. Second and third IOP sets
      were, however, similar indicating stabilisation of IOP measurements. The
      coefficient of repeatability of the instrument between second and third sets was
      4.2 mm Hg for right eyes and 3.6 mm Hg for left eyes. CONCLUSION: The Pulsair
      2000 passes the British standard for reproducibility of a standard test method.

PMID- 7626573
TI  - Clinical comparison of semiconductor diode versus neodymium: YAG non-contact
      cyclo photocoagulation.
AB  - AIMS: The advent of diode lasers has allowed their use in transscleral cyclo
      photocoagulation for refractory glaucoma. A trial was performed to compare the
      ocular hypotensive and inflammatory effects of cyclo photocoagulation using a
      continuous wave diode (810 nm) and a free running neodymium:yttrium aluminium
      garnet (Nd:YAG) laser (1064 nm). METHODS: Forty patients with refractory glaucoma
      were randomised to receive either diode or Nd:YAG therapy. The intraocular
      pressure (IOP) and inflammatory response to treatment were monitored over 3
      months. RESULTS: There was no significant laser related difference in the effect
      on IOP after one treatment. There was, however, a difference in effect in
      retreatments with the IOP lowering effect significantly less, but equally
      sustained in diode retreatment patients. Severe postoperative complications such
      as hyphaema or fibrinous anterior uveitis only occurred in the Nd:YAG group.
      CONCLUSION: The degree and duration of the ocular hypotensive response to cyclo
      photocoagulation appears to be related to the available power output of the
      system used, and the extent of tissue damage.

PMID- 7626574
TI  - Retinal detachment and herpesvirus retinitis in patients with AIDS.
AB  - BACKGROUND: The prolongation of survival of patients with herpesvirus retinitis
      and AIDS has been associated with a rise in the incidence of retinal detachment.
      In such cases, however, retinal reattachment may be difficult to achieve, and
      postoperative visual acuity may be poor despite anatomically successful surgery.
      METHODS: In order to examine factors affecting the visual outcome of surgery, a
      retrospective review of 29 patients with retinal detachment, herpesvirus
      retinitis, and AIDS was performed. Retinal reattachment surgery (32 procedures)
      or prophylactic laser demarcation (five procedures) was performed in 28 eyes of
      23 patients. RESULTS: The macula was attached in 23/28 (82%) eyes at the last
      outpatient visit. Best postoperative visual acuity (median 6/18, range 6/6-hand
      movements) was significantly greater than final postoperative acuity (median
      counting fingers, range 6/6-no perception of light) (Wilcoxon sign rank test, p =
      0.003), and was retained for a median of 3 months (1-91 weeks) after surgery.
      Poor visual outcome as evidenced by submedian final visual acuity was invariably
      associated with persistence of macular detachment, and significantly associated
      with the occurrence of optic atrophy (odds ratio = 5, p = 0.02). CONCLUSION:
      Retinal reattachment surgery appears justified in patients with herpesvirus
      retinitis and AIDS, but postoperative visual deterioration may occur in
      association with optic atrophy.

PMID- 7626575
TI  - Long term ocular and neurological involvement in severe congenital toxoplasmosis.
AB  - AIMS: This study was set up to determine the long term ocular and systemic
      sequelae in patients with severe congenital toxoplasmosis. METHODS: Cross
      sectional and retrospective study of 17 patients with severe congenital
      toxoplasmosis. RESULTS: In addition to chorioretinitis (100%), the most common
      abnormal ocular features were optic nerve atrophy (83%), visual acuity of less
      than 0.1 (85%), strabismus, and microphthalmos. In 50% of cases we observed
      iridic abnormalities and about 40% developed a cataract. Overt endocrinological
      disease, diagnosed in five of 15 patients, included panhypopituitarism (n = 2),
      gonadal failure with dwarfism (n = 1), precocious puberty with dwarfism and
      thyroid deficiency (n = 1), and diabetes mellitus and thyroid deficiency (n = 1).
      The observed endocrinological involvement was associated in all cases with
      obstructive hydrocephalus with a dilated third ventricle and optic nerve atrophy.
      CONCLUSION: The recognition of long term ocular, neurological, and
      endocrinological sequelae of congenital toxoplasmosis is important for medical
      management of these severely handicapped patients.

PMID- 7626576
TI  - Compliance in amblyopia therapy: objective monitoring of occlusion.
AB  - AIM/BACKGROUND: This study aimed to determine the feasibility of objective
      compliance monitoring of amblyopia therapy in clinical research. Occlusion has
      been the mainstay of amblyopia therapy for over 250 years, yet it has never been
      subjected to rigorous evaluation. Treatment regimens range arbitrarily from a few
      minutes to most of the waking hours of the day. Compliance is problematic and as,
      hitherto, accurate objective monitoring has been impossible it is not known how
      much occlusion is required to effect an improvement in vision. METHODS: An
      occlusion dose monitor (ODM) has been developed. The ODM consists of a modified
      occlusion patch and a miniature battery driven datalogger which periodically
      monitors patch skin contact. The patch is a standard disposable item with two
      miniature electrocardiogram electrodes attached to its undersurface. The
      datalogger comprises a high speed static RAM and a clock driven address counter.
      Data are retrieved using an IBM PC/AT computer. Fifteen child amblyopes were
      randomly allocated unilateral occlusion of 1, 4, or 8 hours per day for 4 weeks.
      Owing to data loss, presumed because of accumulation and discharge of static
      electricity, an additional child was included in the 8 hour group. Outcome
      measures were objective (ODM) and subjective (diary) compliance with treatment,
      logMAR visual acuity, and contrast sensitivity. RESULTS: Objective monitoring of
      occlusion is technically feasible and clinically informative. CONCLUSION:
      Objective monitoring of occlusion has opened up new research opportunities which,
      it is hoped, will enable the dose-effect relation of occlusion therapy in the
      various types of amblyopia to be investigated objectively, and facilitate the
      design of effective therapeutic regimens.

PMID- 7626578
TI  - Acanthamoeba, bacterial, and fungal contamination of contact lens storage cases.
AB  - BACKGROUND: Microbial corneal infection is the most serious complication of
      contact lens wear. Contact lens cases are a recognised potential source of
      pathogens associated with corneal ulcers. METHODS: This survey established the
      incidence of protozoal, bacterial, and fungal contact lens case contamination in
      101 asymptomatic daily wear cosmetic contact lens wearers from a domiciliary
      contact lens practice. RESULTS: Eighty two (81%) contact lens cases were found to
      be contaminated, with 19 (19%) sterile. Of all contact lens cases, 78 (77%) grew
      bacteria, 24 (24%) fungi, and 20 (20%) protozoa. Acanthamoeba spp were isolated
      from eight (8%) contact lens cases. Fifty six (55%) contact lens cases yielded
      mixed bacterial contamination. This is the first contact lens case survey in
      which hydrogen peroxide disinfection was the major method of contact lens
      disinfection (75% of subjects) and no home made saline was used. All the
      contaminating organisms were shown to possess the enzyme catalase that breaks
      down hydrogen peroxide to oxygen and water. The polymicrobial nature of the
      biofilms found in many contact lens cases is illustrated electron
      micrographically. CONCLUSION: Based on data from this and previous studies, the
      authors conclude with recommendations for contact lens wearers: (1) regular
      scrubbing of contact lens case interior to disrupt biofilms; (2) exposure of
      contact lens case to very hot water (> or = 70 degrees C) will kill Acanthamoeba
      contaminants; (3) allow contact lens case to air dry between uses; (4) if
      hydrogen peroxide disinfection is preferred, use a two step system; (5) replace
      contact lens case regularly.

PMID- 7626577
TI  - Effect of TNF, IL-1, and IL-6 on the proliferation of human Tenon's capsule
      fibroblasts in tissue culture.
AB  - Trabeculectomy is a commonly performed procedure for primary open angle glaucoma
      and is successful in the majority of cases. However, certain factors including
      aphakia, previous surgery, secondary glaucomas, ethnic origin, and the long term
      use of topical antiglaucoma medications may be associated with a reduced success
      rate. The mechanism (or mechanisms) which influence clinical outcome following
      trabeculectomy remain elusive. Alterations in the composition of the conjunctiva
      or aqueous humour may be partly responsible for this effect, and this could be
      mediated by cytokines. In this study we found that tumour necrosis factor (TNF),
      and interleukin 1 (IL-1) were capable of stimulating the proliferation of Tenon's
      capsule fibroblasts in tissue culture. Interleukin 6 (IL-6) did not appear to
      have any effect. The relevance of this to wound healing following trabeculectomy
      is discussed.

PMID- 7626579
TI  - Topical 0.3% ciprofloxacin, norfloxacin, and ofloxacin in treatment of bacterial
      keratitis: a new method for comparative evaluation of ocular drug penetration.
AB  - AIMS: This study was designed to assess the relative corneal penetration of
      topical drops of three antibiotics and to relate those levels to minimum
      inhibitory concentrations for organisms associated with bacterial keratitis.
      METHODS: Four drops of each of ciprofloxacin, norfloxacin, and ofloxacin (0.3%
      topical ophthalmic preparations) were given to 12 patients undergoing corneal
      transplantation. After the recipient tissue was removed, corneal drug penetration
      was measured using high performance liquid chromatography. RESULTS: Intracorneal
      concentrations of ofloxacin (geometric mean 0.81 mg kg-1) were significantly
      higher than both ciprofloxacin (0.60 mg kg-1; p = 0.048) and norfloxacin (0.54 mg
      kg-1; p = 0.012). Ciprofloxacin and norfloxacin concentrations did not differ
      significantly (p = 0.33). CONCLUSIONS: Review of the minimum inhibitory
      concentrations of the fluoroquinolones against ocular pathogens reveals that
      ciprofloxacin is more potent than ofloxacin against many bacteria; ofloxacin is
      in turn more potent than norfloxacin. These data favour the selection of
      ciprofloxacin and ofloxacin rather than norfloxacin for the empirical treatment
      of corneal infection. The greater potency of ciprofloxacin offsets the superior
      penetration of ofloxacin. There is a need for improved clinical trial data
      concerning the use of fluoroquinolone eyedrops in ulcerative keratitis; some
      encouraging data are available for ciprofloxacin but not (in humans) for
      norfloxacin or ofloxacin.

PMID- 7626581
TI  - Paraneoplastic non-caseating granulomatous inflammation of the eyelid.

PMID- 7626582
TI  - Paraneoplastic retinopathy in association with large cell neuroendocrine
      bronchial carcinoma.

PMID- 7626580
TI  - Analysis of ocular fluids for local antibody production in uveitis.

PMID- 7626583
TI  - Cryptococcus presenting as cloudy choroiditis in an AIDS patient.

PMID- 7626584
TI  - Diagnosis and management of an occult cyclodialysis cleft.

PMID- 7626585
TI  - Influence of exercise-induced maternal stress on fetal outcome in Wistar rats:
      inter-generational effects.
AB  - The effects of physical activity during pregnancy and lactation on the fetal
      outcome and the growth of pups was studied in Wistar rats (n 144). Rats were
      trained to swim for 2 h every day, 6 d/week through pre-pregnancy, pregnancy and
      lactation. Maternal exercise during pregnancy, despite the dams having ad lib.
      access to food, resulted in low-birth-weight pups (5.6 (SD 0.7) g; n 178 in
      exercised dams v. 6.2 (SD 0.8) g; n 238 in sedentary dams). Maternal exercise
      continued through lactation exaggerated further the growth retardation of these
      pups (30.0 (SD 4.7) g; n 78 in exercised dams v. 36.0 (SD 6.9) g; n 126 in
      sedentary dams). The effects of maternal exercise during pregnancy and lactation
      studied over two successive generations revealed a reduction in the growth rates
      of the second generation progeny of both exercised (5.3 (SD 0.9) g; n 125 at
      birth and 25.1 (SD 6.8) g; n 54 at weaning) and sedentary rats (6.0 (SD 0.2) g; n
      110 at birth and 31.3 (SD 4.3) g at weaning) born to first-generation exercised
      rats. While slower growth in the former indicates a cumulative effect of exercise
      stress over two generations, that of the latter indicates that the generational
      effects are manifest even though the dams of the F1 generation were not exposed
      to exercise stress during pregnancy and lactation. These findings suggest that
      the adverse effect of maternal exercise during pregnancy and lactation on fetal
      outcome in one generation is transferred to the subsequent generation.

PMID- 7626586
TI  - Dietary intakes of starch and non-starch polysaccharides in a west African
      village.
AB  - Dietary intakes of starch and non-starch polysaccharides (NSP) have been
      estimated for a rural West African community. These people eat directly from
      shared bowls of cooked food, and so measurement of any individual's food intake
      is not possible. Recently developed methodology for estimating food intake under
      these circumstances and the analysis of samples for dietary polysaccharides are
      combined to yield estimates of intakes of about 375 g starch and 25 g NSP/d for
      adult males, with lower intakes for women and children, related to their smaller
      body weights. These intakes are not direct measurements but are extremely
      plausible when compared with values obtained for other societies where the
      complication of the shared food bowl does not impinge upon the measurements.

PMID- 7626587
TI  - Hepatic detoxification of ammonia in the ovine liver: possible consequences for
      amino acid catabolism.
AB  - The effects of either low (25 mumol/min) or high (235 mumol/min) infusion of
      NH4Cl into the mesenteric vein for 5 d were determined on O2 consumption plus
      urea and amino acid transfers across the portal-drained viscera (PDV) and liver
      of young sheep. Kinetic transfers were followed by use of 15NH4Cl for 10 h on the
      fifth day with simultaneous infusion of [1-13C]leucine to monitor amino acid
      oxidation. Neither PDV nor liver blood flow were affected by the additional NH3
      loading, although at the higher rate there was a trend for increased liver O2
      consumption. NH3-N extraction by the liver accounted for 64-70% of urea-N
      synthesis and at the lower infusion rate the additional N required could be more
      than accounted for by hepatic removal of free amino acids. At the higher rate of
      NH3 administration additional sources of N were apparently required to account
      fully for urea synthesis. Protein synthesis rates in the PDV and liver were
      unaffected by NH3 infusion but both whole-body (P < 0.05) and splanchnic tissue
      leucine oxidation were elevated at the higher rate of administration. Substantial
      synthesis of [15N]glutamine occurred across the liver, particularly with the
      greater NH3 supply, and enrichments exceeded considerably those of glutamate. The
      [15N]urea synthesized was predominantly as the single labelled, i.e. [14N15N],
      species. These various kinetic data are compatible with the action of ovine
      hepatic glutamate dehydrogenase (EC 1.4.1.2) in periportal hepatocytes in the
      direction favouring glutamate deamination. Glutamate synthesis and uptake is
      probably confined to the perivenous cells which do not synthesize urea.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7626588
TI  - The influence of dietary fibre on body composition, visceral organ weight,
      digestibility and energy balance in rats housed in different thermal
      environments.
AB  - The present study was undertaken to provide detailed information on the effect of
      dietary fibre (DF) level on body composition, visceral organ weight, nutrient
      digestibility and on energy and protein metabolism of rats housed in cold (16
      degrees), warm (24 degrees) or hot (32 degrees) thermal environments. High- or
      low-fibre diets (257 v. 56 g DF/kg dry matter (DM)) were studied in a 6-week
      balance experiment (initial body weight about 100 g). Heat production was
      measured using open-air circuit respiration chambers. Pea fibre and pectin were
      used to adjust the DF level in the high-fibre diet. The ranking order of daily
      gain of rats kept in different environments was: 24 degrees > 16 degrees > 32
      degrees, while the ranking order for carcass protein was: 16 degrees > 24 degrees
      > 32 degrees. Rats on the high-DF diet had a lower daily gain than those on the
      low DF diet, and more protein in DM of empty body weight (EBW) and less fat. The
      relative weights (g/kg EBW) of liver, heart and kidney decreased when increasing
      the environmental temperature. The relative weight of the heart was highest in
      rats on the high DF level, while liver and kidney weights were unaffected by DF.
      Per kg EBW, the stomach, small intestine, caecum and colon and the length of
      colon were significantly greater in rats consuming the high-fibre diet compared
      with those on the low-fibre diet. Rats kept at low temperature had a
      significantly heavier gastrointestinal (GI) tract than those kept at the highest
      temperature. Digestibility of protein, DM and energy was lowest for rats fed on
      the high-fibre diet. Heat production (HP) of fed rats as well as fasting HP
      decreased significantly as environmental temperature increased. HP as a
      proportion of metabolizable energy (ME) was significantly lower for rats at 24
      degrees compared with the other environmental temperatures. The proportion of
      energy retained as protein was slightly higher in rats fed on the high-fibre than
      on the low-fibre diet. Based on the results of the present study the authors
      measured a net energy value of 5.4 kJ/g DF fermented; approximately 50% of the DF
      came from peas. Possible implications of the present findings are discussed.

PMID- 7626589
TI  - The effect of a probiotic on faecal and liver lipid classes in rats.
AB  - The effect of a probiotic composed of Bacillus, Lactobacillus, Streptococcus,
      Saccharomyces and Candida species (each at 10(7-8) colony-forming units (cfu)/g
      rice bran), given at a level of 150 g/kg diet for 6 weeks, on lipid metabolism
      was examined in the faeces, serum and liver of male rats. Liver weight decreased
      35% in the rats fed on a high-fat, high-cholesterol diet containing the
      probiotic. Total cholesterol concentration in the serum was significantly lower
      in the probiotic group than in the control group throughout the experimental
      period in rats fed on the high-fat, high-cholesterol diet, and HDL-cholesterol
      concentration was significantly higher (P < 0.05) in the probiotic group than in
      the control group which was fed for the 6 week experimental period on a basal
      diet. The serum VLDL+IDL+LDL cholesterol concentration in the probiotic groups
      were reduced compared with those of the corresponding control groups. The
      probiotic groups fed on the high-fat, high-cholesterol diet and the basal diet
      had lower hepatic cholesterol concentrations than did the corresponding control
      groups (P < 0.05). Hydroxymethylglutaryl coenzyme A reductase (NADPH) (EC
      1.1.1.34) activity in the liver was lower in rats fed on the high-fat, high
      cholesterol diet with the probiotic. The neutral and acidic steroid
      concentrations in faeces were higher in the probiotic group than in the control
      group fed on the high-fat, high-cholesterol diet. Escherichia coli decreased and
      Bifidobacterium and Eubacterium increased in the faecal microflora of rats fed on
      the dietary probiotic. Lactobacillus in the probiotic groups was higher than that
      in the control groups. The present study shows that the probiotic promotes
      Bifidobacterium and Eubacterium in the faecal microflora, and reduces cholesterol
      levels in the serum and liver of rats.

PMID- 7626590
TI  - Analysis of cyclic feed intake in rats fed on a zinc-deficient diet and the level
      of dihydropyrimidinase (EC 3.5.2.2).
AB  - The body weight and feed intake of rats fed on a Zn-deficient diet for 28 d were
      reduced compared with those of control rats. The feed intakes of the Zn-deficient
      and control groups during the period were 10.2 (SE 0.3) and 15.7 (SE 0.2) g/d
      respectively. Cyclic variations in feed intake and body-weight changes were found
      in analysis not only of all the data for five rats but also that in each
      individual rat. Cosinor analysis revealed that the cyclical period of both the
      feed intake and body-weight change in the Zn-deficient rats was 3.5 (SE 0.1) d.
      The mesor and amplitude value of the feed intake in the Zn-deficient rats was
      10.1 (SE 0.4) g/d and 3.5 (SE 0.5) g/d respectively, and that of body-weight
      change was 1.4 (SE 0.1) g/d and 7.9 (SE 1.3) g/d respectively. Among pyrimidine
      catabolizing enzymes, dihydropyrimidinase (EC 3.5.2.2) activity showed
      significant retardation in the Zn-deficient rat liver with decrease of the enzyme
      protein. The ratio of apo-form to holo-form dihydropyrimidinase in the liver was
      not affected by the Zn-deficient diet.

PMID- 7626591
TI  - Lipid-zinc interaction: its effect on the testes of mice.
AB  - Lipid-Zn interaction in the testes of mice was studied by feeding them low-fat
      (30 g maize oil/kg; group LFZD) and high-fat (90 g maize oil/kg; group HFZD) Zn
      deficient diets for 6 weeks. The results were compared with those of
      corresponding Zn-supplemented-diet-fed controls (groups LFZS and HFZS). The
      integument-related Zn-deficiency symptoms appeared in group HFZD and not in group
      LFZD mice despite lack of Zn in their ration and an equal level of Zn in their
      blood serum. The feed intake, gain in body weight and testes weight of the LFZD
      group were comparable with those of the LFZS and HFZS groups (P > 0.05) but were
      higher than those of the group HFZD (P < 0.05). The testes of group HFZD
      displayed necrotic changes marked by the presence of giant cells, lower RNA, DNA
      and protein concentrations and higher phospholipid and cholesterol levels than
      those of mice in the LFZD group. The concentrations of these fractions were not
      significantly different between LFZD and HFZS. The results do not support the
      hypothesis that Zn is essential either for testicular function or for nucleic
      acid and protein synthesis in animals fed on a low-fat diet; however, it appears
      to be essential for animals fed on a high-fat diet. The changes observed in the
      testes of the HFZD animals suggest the excess intake of fat as their cause in Zn
      deficient animals.

PMID- 7626592
TI  - Chronic and postprandial responses of plasma insulin, glucose and lipids in
      volunteers given dietary fibre supplements.
AB  - We questioned whether a dietary fibre supplement known to lower fasting plasma
      cholesterol concentrations can also lower the postprandial plasma cholesterol,
      glucose and insulin concentrations when it is administered just before a meal.
      Two studies were conducted in healthy middle-aged volunteers of both sexes in
      whom the fasting plasma total cholesterol concentrations were above normal. In
      the first study the dietary fibre treatments (2.2 g) were psyllium and a psyllium
      citrus pectin mixture to which the subjects (four males, eight females) had no
      prior exposure. Controls received no supplement. The meals were high-fat
      breakfasts and lunches. In the second study the dietary fibre (6 g) was from
      sugar-beet root and the reference control was alpha-cellulose (2 g); the meal was
      of glucose. The volunteers (eight males, eight females) had prior exposure to the
      fibre supplements three times daily for 3 weeks. After adjustments for fasting
      values and changes in haemodilution, the psyllium and psyllium-citrus pectin
      mixture in the first experiment had no significant effects on the postprandial
      measurements of plasma glucose, insulin:glucose ratio, total-, LDL- and HDL
      cholesterol, and triacylglycerol. By contrast, the sugar-beet fibre in the second
      study significantly decreased the area under the glucose response curve by 6.9%,
      the area under the insulin response curve was lower by 9.6%, although not
      significantly, and the post-glucose meal HDL-cholesterol concentration was
      significantly (12%) higher. Additionally, the 3-week treatment with sugar-beet
      fibre significantly lowered the fasting total- and LDL-cholesterol
      concentrations, by 8.5% and 9.6% respectively. We conclude that low doses of
      psyllium and citrus pectin at breakfast and lunch have no effects on the
      postprandial plasma measurements, but that sugar-beet fibre taken daily for 3
      weeks affects both fasting and postprandial plasma metabolites favourably in
      these individuals with mildly increased risk of ischaemic heart disease. Further,
      we observed that small changes in haemodilution occur after meals, as indicated
      by plasma albumin concentration and packed cell volume. Underemphasis of the
      dietary fibre effects may occur when postprandial haemodilution is not taken into
      account.

PMID- 7626593
TI  - The responses of blood galactose to oral doses of lactose, galactose plus glucose
      and milk to piglets.
AB  - The capacity of intestinal lactase (EC 3.2.1.23) of piglets to hydrolyse lactose
      in vivo was investigated by measuring the response of blood galactose to doses of
      lactose, galactose plus glucose and both whole and skimmed milk. Following the
      administration of oral doses of lactose dissolved in water to piglets from 2 to
      18 d of age the adjusted galactose area under the curve (AUC) was between 1.12
      and 1.36 arbitrary units, while following a dose of galactose plus glucose
      dissolved in water it was between 1.56 and 1.98 arbitrary units. Whereas these
      results suggest that the rate of digestion of lactose appeared to limit the
      amount of galactose reaching the peripheral blood after a dose of lactose
      dissolved in water, there was no significant correlation between the capacity of
      piglets to hydrolyse physiological amounts of lactose and the age of the piglets
      (2- to 18-d-old piglets; r 0.11). Following oral doses of sow's milk containing
      either lactose, or galactose plus glucose, the adjusted galactose AUC values were
      0.94 and 1.00 arbitrary units respectively, in 10-d-old piglets. Thus, the
      limitation to the digestion of lactose observed when it was present in water was
      not evident for lactose in sow's milk. Since there was no significant difference
      between the adjusted galactose AUC following a dose of whole milk (0.95 arbitrary
      units) and that following a dose of skimmed milk (1.03 arbitrary units), the
      presence of fat in sow's milk did not appear to affect the utilization of lactose
      by the sucking piglets.

PMID- 7626594
TI  - Abomasal glucose, maize starch and maize dextrin infusions in cattle: small
      intestinal disappearance, net portal glucose flux and ileal oligosaccharide flow.
AB  - Three castrated male Holstein cattle (423 (SD 19)kg live weight) fitted with
      elevated carotid artery, portal, and mesenteric venous catheters, and abomasal
      and ileal cannulas were used to study small-intestinal starch digestion. The
      cattle were infused abomasally with water (275 ml/h), glucose (66 g/h), maize
      dextrin (66 g/h) or maize starch (66 g/h) in an incomplete Latin square design,
      with eight infusion periods. Infusion with carbohydrate resulted in higher
      arterial glucose concentrations and greater net portal glucose flux than when
      cattle were infused with water. Arterial glucose concentration and net portal
      glucose flux were highest when glucose was infused. In the small intestine, 85%
      of abomasally-infused glucose, 78% of infused dextrin, and 66% of infused starch
      disappeared. Of the carbohydrate that disappeared in the small intestine, that
      which could be accounted for as net portal glucose flux was 73% for glucose, 60%
      for dextrin, and 57% for starch. Ileal digesta contained unpolymerized glucose,
      and short-chain soluble alpha-glucoside. Of the infused dextrin flowing past the
      ileum (14 g/h), 0.3 g/h was glucose, 6.2 g/h was soluble alpha-glucoside, and 7.5
      g/h was insoluble alpha-glucoside. Of the infused starch flowing at the ileum
      (22.2 g/h), 0.9 g/h was glucose, 5.3 g/h was soluble alpha-glucoside, and 15.9
      g/h was insoluble alpha-glucoside. The average chain lengths of the soluble alpha
      glucosides in ileal digesta were 2.07 and 2.36 for dextrin and starch infusions
      respectively, indicating mostly di- and to a lesser extent trisaccharides. We
      conclude that (1) when 66 g raw starch is presented to the small intestine per h,
      about half of the intestinal disappearance appears as glucose in the portal
      vasculature, and (2) alpha-1,4 glucosidase (EC 3.2.1.20) activity at the brush
      border is the rate-limiting step to small-intestinal starch digestion in cattle.

PMID- 7626595
TI  - Caecal and faecal short-chain fatty acids and stool output in rats fed on diets
      containing non-starch polysaccharides.
AB  - The exact mechanisms by which non-starch polysaccharides increase stool output
      are unknown. In the present study the hypothesis that the site of fermentation
      and short-chain fatty acid (SCFA) accumulation is related to the action of non
      starch polysaccharides (NSP) on stool output was tested. The basal diet (45 g
      NSP/kg) of forty-three male Wistar rats was supplemented with 50 g/kg of either
      guar, karaya, tragacanth, gellan, xanthan or ispaghula for 28 d. A further twenty
      three rats were maintained on the basal diet for the same time period. Faeces
      were then collected over 2 d and caecal contents obtained post-mortem. Caecal and
      faecal wet and dry weights and SCFA were measured. Each supplement had a
      different effect on the caecal and faecal contents but they appeared to fall into
      three groups when compared with the basal diet. In group 1, guar gum affected
      only caecal SCFA. It had no effect on stool output or faecal SCFA. In group 2,
      karaya increased caecal SCFA and tragacanth, karaya and xanthan increased faecal
      SCFA and faecal water. In group 3, ispaghula and gellan had no consistent effect
      on caecal or faecal SCFA concentrations but increased total faecal SCFA output
      and increased faecal wet and dry weight. Although the knowledge that SCFA are
      rapidly absorbed in the large intestine has led us to believe that they play no
      role in determining faecal output, these results suggest that in some cases where
      NSP are slowly fermented, and increase faecal SCFA, the role of the SCFA may need
      to be reassessed.

PMID- 7626596
TI  - Influence of a mixed and a vegetarian diet on urinary magnesium excretion and
      concentration.
AB  - Urinary Mg is suggested to be an effective inhibitor of the formation and growth
      of calcium oxalate stones. In order to examine the influence of variations in
      dietary Mg on urinary Mg excretion, ten healthy male subjects were kept on two
      different standard diets for 5 d each. In the course of the test period, 24 h
      urine samples were collected. Diets 1 and 2 were calculated according to the
      dietary recommendations of the German Society of Nutrition (Deutsche Gesellschaft
      fur Ernahrung, 1986). Diet 1 was established as a model of a balanced mixed diet,
      whereas diet 2 represented an ovo-lacto-vegetarian meal plan. Diets 1 and 2 were
      isoenergetic with equal amounts of the main nutrients, estimated from food
      tables, and a constant fluid intake. In contrast to the content of Mg (336 mg)
      and dietary fibre (28 g) of diet 1, diet 2 was rich in Mg (553 mg) and dietary
      fibre (52 g). On the ingestion of diet 1, renal Mg excretion was 5.09 (SEM 0.35)
      mmol on the control day and increased slightly but not significantly to 5.40 (SEM
      0.52) mmol on the corresponding day on diet 2. Urinary Mg excretion as a
      percentage of estimated dietary intake was about double on the balanced mixed
      diet (37%) than on the Mg-rich vegetarian diet (24%). As both diets contained
      equal amounts of most nutrients, these results indicate a lower excretion rate of
      Mg from the vegetarian diet than from the mixed diet.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7626597
TI  - Gating of thrombin in platelet aggregates by pO2-linked lowering of extracellular
      Ca2+ concentration.
AB  - Platelet accretion at sites of vascular injury yields a neo-tissue comprising
      packed platelets and having an interstitial space not supplied with blood. Within
      growing thrombi platelet masses become anoxic and depolarize to yield
      interstitial cation concentrations characteristic of the more voluminous platelet
      cytosol, with extracellular [Ca2+] falling below that adequate to support the
      plasma clotting system. The platelet-associated clotting system reactivates
      during disaggregation of the thrombi in vitro, which proceeds with high yield of
      apparently basal, functional platelets when specific anticoagulants are included
      in the disaggregating media. The capacity of regulatory demand to lower
      extracellular [Ca2+] in the microenvironment of platelet aggregates provides a
      physiological basis for evolution of the highly cooperative calcium interactions
      of the hemostasis system.

PMID- 7626598
TI  - Kinetic characterization and cross-resistance patterns of HIV-1 protease mutants
      selected under drug pressure.
AB  - Eleven different recombinant, drug-resistant HIV-1 protease (HIV PR) mutants-
      R8Q, V32I, M46I, V82A, V82F, V82I, I84V, V32I/I84V, M46I/V82F, M46I/I84V, and
      V32I/K45I/F53L/A71V/I84V/L89M--were generated on the basis of results of in vitro
      selection experiments using the inhibitors A-77003, A-84538, and KNI-272. Kinetic
      parameters of mutant and wild-type (WT) enzymes were measured along with
      inhibition constants (Ki) toward the inhibitors A-77003, A-84538, KNI-272, L
      735,524, and Ro31-8959. The catalytic efficiency, kcat/Km, for the mutants
      decreased relative to WT by a factor of 1.2-14.8 and was mainly due to the
      elevation of Km. The effects of specific mutations on Ki values were unique with
      respect to both inhibitor and mutant enzyme. A new property, termed vitality,
      defined as the ratio (Kikcat/Km)mutant/(Kikcat/Km)WT was introduced to compare
      the selective advantage of different mutants in the presence of a given
      inhibitor. High vitality values were generally observed with mutations that
      emerged during in vitro selection studies. The kinetic model along with the panel
      of mutants described here should be useful for evaluating and predicting patterns
      of resistance for HIV PR inhibitors and may aid in the selection of inhibitor
      combinations to combat drug resistance.

PMID- 7626599
TI  - Relationship between equilibrium amide proton exchange behavior and the folding
      pathway of barnase.
AB  - We describe a three-part strategy for analyzing the relationship between
      equilibrium amide proton exchange behavior of barnase and its folding/unfolding
      pathway. First, the effects of mutation on stability and kinetics are compared to
      reveal which residues exchange by local breathing, which by local unfolding, and
      which by a mixture of the two mechanisms. Second, is to detect any change of
      mechanism between EX2 and EX1 from the pH dependence of exchange and its
      relationship to structure and kinetics. The third is to determine from which
      state exchange takes place for residues that nominally exchange by a global
      process: the fully unfolded state or the folding intermediate. Experiments were
      performed at values of pH and temperature around physiological and close to
      conditions under which the folding pathway of barnase has been studied in detail.
      A set of residues was found for which the rate constants for exchange change on
      mutation by exactly the same factor as does the equilibrium constant for
      unfolding. Further, the protection factor against exchange for these residues in
      wild-type barnase is very similar to the equilibrium constant for overall folding
      measured by differential scanning calorimetry and extrapolated to the identical
      reaction conditions. These residues clearly exchange by a global unfolding
      mechanism, and the protection factors are consistent with the denatured state of
      barnase being largely as unprotected as model peptides. The rate constants for
      exchange of a second set of residues are unaffected by distant mutations, and so
      these exchange by local breathing. The logarithms of the rate constants (log kex)
      increase linearly with pH for the locally exchanging residues, consistent with
      the kinetics of the EX2 mechanism at these values of pH. The pH dependence for
      the globally exchanging residues, however, indicates a switch away from EX2
      between pH 6.7 and 7.9 at 37 degrees C. The state from which "global" exchange
      occurs was probed also by using mutants in which the folded state of each is
      destabilized by the same amount by mutation relative to the unfolded state but
      the destabilization of the folding intermediate varies considerably. Under EX2
      conditions, the changes in kex for all these residues follow the overall
      destabilization, confirming that exchange occurs from the fully unfolded state,
      not from the folding intermediate. The common characteristic of the residues that
      exchange by global unfolding is that they are all buried within the protein.

PMID- 7626600
TI  - Inhibition of mouse erythroid band 3-mediated chloride transport by site-directed
      mutagenesis of histidine residues and its reversal by second site mutation of Lys
      558, the locus of covalent H2DIDS binding.
AB  - Substitution by site-directed mutagenesis of any one of the histidine residues
      H721, H837, and H852 by glutamine, or of H752 by serine, inhibits Cl- flux
      mediated by band 3 expressed in Xenopus oocytes. Mutation of Lys 558 (K558N), the
      site of covalent binding of H2DIDS (4,4'-diisothiocyanostilbene-2,2'-disulfonate)
      in the outer membrane surface, in combination with any one of the His/Gln
      mutations leads to partial (H721Q; H837Q) or complete (H852Q) restoration of Cl-
      flux. In contrast, inhibition of Cl- flux by mutation of proline or lysine
      residues in the vicinity of His 837 at the inner membrane surface cannot be
      reversed by the second-site mutation K558N, indicating specificity of interaction
      between Lys 558 and His 837. The histidine-specific reagent diethyl pyrocarbonate
      (DEPC) is known to inhibit band 3-mediated anion exchange in red blood cells
      [Izuhara, K., Okubo, K., & Hamasaki, N. (1989) Biochemistry 28, 4725-4728]. It
      was also found to inhibit transport after expression in the oocyte of wild-type
      band 3, of the double mutants of the histidines listed above, and of the single
      mutant H752S. The effects on the wild type and the double mutants were
      indistinguishable, while the mutant H752S exhibited a considerably reduced
      sensitivity to inhibition, suggesting that His 752 is the most prominent site of
      action of DEPC. According to a hydrophobicity plot of band 3 and further
      independent evidence, Lys 558, the mutated histidines, and Glu 699, the mutation
      of which was also found to inhibit Cl- flux [Muller-Berger, S., Karbach, D.,
      Kang, D., Aranibar, N., Wood, P. G., Ruterjans, H., & Passow, H. (1995)
      Biochemistry 34, 9325-9332], are most likely located in five different
      transmembrane helices. The interactions between Lys 558 and the various
      histidines suggest that these helices reside in close proximity. Together with
      the helix carrying Glu 699, they could form an access channel lined with an array
      of alternating histidine and glutamate residues. Together with a chloride ion
      bridging the gap between His 852 and His 837, they could have the potential to
      form, at low pH, a transmembrane chain of hydrogen bonds. The possible functional
      significance of such channel is discussed.

PMID- 7626601
TI  - Roles of histidine 752 and glutamate 699 in the pH dependence of mouse band 3
      protein-mediated anion transport.
AB  - In the accompanying paper we have shown that four different histidine residues
      are involved in the maintenance of mouse band 3 in a state in which it is able to
      execute its anion transport function. Here we focus on the functional
      significance of His 752 and demonstrate that this residue, together with Glu 699,
      plays a key role in the control of pH dependence of Cl- transport. Mouse band 3
      encoding cRNA was expressed in Xenopus oocytes, and band 3-mediated Cl- transport
      was measured at zero membrane potential over the pH range 6.0-9.2. Transport
      decreased with increasing H+ concentration and was governed by a single pK of
      5.8. After correction for temperature differences, this result agrees well with
      measurements in erythrocyte ghosts of Cl- flux by Funder and Wieth [Funder, J., &
      Wieth, J. O. (1976) J. Physiol. 262, 679-698] and our own determinations by 35Cl
      NMR spectroscopy of Cl- exchange between the substrate binding site and the
      medium. After mutation of either Glu 699 to Asp or of His 752 to Ser, the maximal
      rate of transport is reduced and the rate of anion exchange is now governed by a
      single pK of about 6.8-6.9. This suggests that the formation of a hydrogen bond
      between His 752 and Glu 699 is essential for the decrease of band 3-mediated Cl-
      transport at low pH. We suggest that in the wild type band 3 both the decrease of
      the chloride exchange between the medium and the substrate binding site and the
      inhibition of chloride translocation across the membrane are dominated by a
      common rate-limiting step and that this step involves hydrogen bond formation
      between Glu 699 and His 752.

PMID- 7626602
TI  - Photoregeneration of bovine rhodopsin from its signaling state.
AB  - In rhodopsin, 11-cis-retinal is bound by a protonated Schiff base and acts as a
      strong antagonist, which holds the receptor in its inactive ground state
      conformation. Light induces cis-/trans-retinal isomerization and a sequence of
      thermal transitions through intermediates. The active conformation that catalyzes
      GDP/GTP exchange in the G-protein (Gt) is generated from the metarhodopsin II
      intermediate (MII) and mediated by Schiff base proton translocation and proton
      uptake from the aqueous phase. In the stable nucleotide-free MII-Gt complex, any
      thermal transition of MII into other forms of rhodopsin is blocked. We have now
      studied how Gt affects flash-induced photochemical conversions of MII. Difference
      spectra from measured absorption changes show that MII photolyzes through two
      parallel pathways, with fast (1 ms) and slow (50 ms) kinetics (12 degrees C, pH
      6). The slow pathway regenerates rhodopsin (9- or 11-cis) via Schiff base
      reprotonation and proton release. We infer a cis-isomerized early photoproduct
      (reverted meta, RM) preceding these thermal transitions. When MII is photolyzed
      in the MII-Gt complex, the slow absorption change is abolished, indicating that
      Gt blocks the completion of the regeneration process. This is due to the
      formation of a stable RM-Gt complex, as shown by successive photolysis of MII,
      RM, and ground state rhodopsin, and the application of GTP gamma S at different
      stages. The complex dissociates with GTP gamma S, and rhodopsin relaxes to the
      ground state. The results indicate that cis-retinal and Gt can bind to the
      receptor at the same time. We discuss the result that the protonations in the
      meta II state uncouple retinal geometry from Gt interaction.

PMID- 7626603
TI  - Insulin-stimulated phosphorylation of recombinant pp120/HA4, an endogenous
      substrate of the insulin receptor tyrosine kinase.
AB  - Insulin binding to the alpha-subunit of its receptor stimulates the receptor
      tyrosine kinase to phosphorylate the beta-subunit and several endogenous protein
      substrates, including pp120/HA4, a liver-specific plasma membrane glycoprotein of
      M(r) 20,000. Analysis of the deduced amino acid sequence of rat liver pp120/HA4
      revealed two potential sites for tyrosine phosphorylation in the cytoplasmic
      domain (Tyr488 and Tyr513), as well as a potential cAMP-dependent protein kinase
      phosphorylation site (Ser503). To determine which of these sites is
      phosphorylated in response to insulin, each of these amino acid residues was
      altered by site-directed mutagenesis. Mutant cDNAs were then expressed by stable
      transfection in NIH 3T3 cells. Two mutations (Phe488 and Ala503) impaired insulin
      induced phosphorylation of pp120/HA4, suggesting that pp120/HA4 undergoes
      multisite phosphorylation. It seems likely that Tyr488 is phosphorylated by the
      insulin receptor kinase, and phosphorylation of Ser513 may contribute to the
      regulation of tyrosine phosphorylation. Since pp120/HA4 is believed to be
      associated with a Ca2+/Mg(2+)-dependent ecto-ATPase activity, we determined the
      effects of insulin-induced phosphorylation on this enzymatic activity. In NIH 3T3
      cells co-expressing the insulin receptor and pp120/HA4, insulin caused a 2-fold
      increase in ecto-ATPase activity. Moreover, elimination of the phosphorylation
      sites of pp120/HA4 impaired the ability of insulin to stimulate the ecto-ATPase
      activity. These data suggest that tyrosine phosphorylation of pp120/HA4 may
      regulate Ca2+/Mg(2+)-dependent ecto-ATPase activity.

PMID- 7626604
TI  - Coordination of Ca2+ by the pore region glutamates is essential for high-affinity
      dihydropyridine binding to the cardiac Ca2+ channel alpha 1 subunit.
AB  - The molecular determinants for Ca2+ modulation of dihydropyridine (DHP) binding
      to cardiac Ca2+ channels were identified by mutational neutralization of the
      glutamate residues that comprise the Ca2+ channel selectivity filter. The binding
      activity of the DHP (+)-[3H]isradipine, monitored after expression of wild-type
      and mutant alpha 1 subunits in COS-7 cells, was markedly reduced in four single
      mutants and a double mutant. Evidence for decreased Ca2+ affinity was obtained
      for two single mutants in kinetic and equilibrium binding studies. Mutational
      destabilization of Ca2+ binding resulted in a concomitant decrease of (+)
      [3H]isradipine binding affinity. Recovery of (+)-[3H]isradipine binding activity
      by the allosteric modulator (+)-tetrandrine in two single mutants was associated
      with a recovery of Ca2+ and DHP binding kinetics to wild-type values. Our
      findings demonstrate that high-affinity DHP binding is dependent on Ca2+
      coordination by glutamate residues which form the selectivity filter of the
      channel pore.

PMID- 7626605
TI  - Interleukin-3-associated expression of gangliosides in mouse myelogenous leukemia
      NFS60 cells introduced with interleukin-3 gene: expression of ganglioside GD1a
      and key involvement of CMP-NeuAc:lactosylceramide alpha 2-->3-sialyltransferase
      in GD1a expression.
AB  - Murine interleukin-3 (IL-3)-associated expression of gangliosides has been
      investigated using a gene transfection technique. A murine IL-3 cDNA was
      introduced into the parental NFS60-17 cells that was exclusively dependent on IL
      3. We analyzed the glycosphingolipids from the parental cells and the transfected
      cells by fast atom bombardment mass spectrometry analyses and/or immunostaining
      techniques using specific antibodies. Two major gangliosides, IV3NeuAc-GgOse4Cer
      (GM1b) and IV3-NeuAc,III6NeuAc-GgOse4Cer (GD1 alpha), were expressed, in the
      parental cells. By contrast, in the IL-3 gene-transfected cells, a ganglioside
      IV3NeuAc,II3NeuAc-GgOse4Cer (GD1a) was strikingly expressed, in addition to GM1b
      and GD1 alpha that were already present in the parental cells. In spite of
      various IL-3-secreting capabilities, all transfectants investigated have
      exhibited the same ganglioside patterns and expressed GD1a. Furthermore, the
      appearance of GD1a was a consequence of the up-regulation of a single
      glycosyltransferase, CMP-NeuAc:lactosylceramide alpha 2-->3-sialytransferase (GM3
      synthase). Activities of the other downstream glycosyltransferases that were
      involved in GD1a synthesis were not significantly different between the parental
      and the transfected cells. According to these data, the progression of tumor
      stage by the acquisition of autonomous cell growth ability after IL-3 gene
      transfection resulted in dramatic changes in cell surface gangliosides and their
      biosynthetic pathways. GD1a could be considered as an IL-3-associated ganglioside
      and was expressed in a tight connection with a single glycosyltransferase (GM3
      synthase) up-regulation and with IL-3 expression in murine myelogenous leukemia
      cells.

PMID- 7626606
TI  - Helix packing in the sucrose permease of Escherichia coli: properties of
      engineered charge pairs between helices VII and XI.
AB  - Of four putative intramembrane charge pairs in lactose permease, only three are
      conserved in the homologous sucrose permease of Escherichia coli [Bockmann, J.,
      Heuel, H., & Lengeler, J. W. (1992) Mol. Gen. Genet. 235, 22-32]. The missing
      charge pair was introduced into wild-type sucrose permease by site-directed
      mutagenesis of Asn234 (helix VII) and Ser356 (helix XI). Individual replacement
      of either residue with a charged amino acid abolishes active sucrose transport
      with the exception of the Asn234-->Asp mutant. However, simultaneous replacement
      of Asn234 with Asp or Glu and Ser356 with Arg or Lys results in high activity.
      Thus, an acidic residue at position 234 rescues the activity of the Ser356-->Arg
      or Ser356-->Lys mutant, and a basic residue at position 356 rescues the activity
      of the Asn234-->Glu mutant. Furthermore, when expressed at a relatively low rate,
      the double mutant Asn234-->Asp/Ser356-->Arg is present in the membrane in a
      significantly greater amount than wild-type, suggesting that the charge pair
      improves insertion of sucrose permease into the membrane. The results indicate
      that helices VII and XI of sucrose permease are in close proximity and that a
      charge pair interaction can be established between residues 234 (helix VII) and
      356 (helix XI). However, interchange of the acidic residue at position 234 with
      the basic residue at position 356 abolishes sucrose transport.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7626607
TI  - Cysteine scanning mutagenesis of helix V in the lactose permease of Escherichia
      coli.
AB  - Using a functional lactose permease mutant devoid of Cys (C-less permease), each
      amino acid residue in putative transmembrane helix V was replaced individually
      with Cys (from Met145 to Thr163). Of the 19 mutants, 13 are highly functional (60
      125% of C-less permease activity), and 4 exhibit lower but significant lactose
      accumulation (15-45% of C-less permease). Cys replacement of Gly147 or Trp151
      essentially inactivates the permease (< 10% of C-less); however, previous studies
      [Menezes, M. E., Roepe, P. D., & Kaback, H. R. (1990) Proc. Natl. Acad. Sci.
      U.S.A. 87, 1638; Jung, K., Jung, H., et al. (1995) Biochemistry 34, 1030]
      demonstrate that neither of these residues is important for activity. Immunoblots
      reveal that all of the mutant proteins are present in the membrane in amounts
      comparable to C-less permease with the exception of Trp151-->Cys and single
      Cys154 permeases which are present in reduced amounts. Finally, only three of the
      single-Cys mutants are inactivated significantly by N-ethylmaleimide (Met145-
      >Cys, native Cys148, and Gly159-->Cys), and the positions of the three mutants
      fall on the same face of helix V.

PMID- 7626608
TI  - Refolding by disulfide isomerization: the mixed disulfide between ribonuclease T1
      and glutathione as a model refolding substrate.
AB  - Protein folding, associated with isomerization of disulfide bonds, was studied
      using the mixed disulfide between glutathione and reduced ribonuclease T1 (GS
      RNase T1) as a stable soluble and homogeneous starting material; conditions were
      selected to model those within the lumen of the endoplasmic reticulum where
      native disulfide bonds are formed in protein biosynthesis. Folding was initiated
      by addition of free glutathione (GSH +/- GSSG) to promote thiol-disulfide
      interchange and was monitored by intrinsic protein fluorescence, appearance of
      native ribonuclease activity, HPLC, and nonreducing SDS-PAGE. All the analyses
      indicated that native RNase T1 was recovered in high yield in a variety of redox
      conditions. Appearance of native activity followed first-order kinetics; kinetic
      analysis of the intrinsic fluorescence changes indicated an additional rapid
      process in some conditions, interpreted as the formation of a nonnative
      intermediate state. Analysis by HPLC and SDS-PAGE also indicated the formation of
      transient intermediates. In 1.5 M NaCl, GS-RNase T1 adopts a compact native-like
      conformation; refolding by thiol-disulfide interchange in these conditions was
      accelerated approximately 2-fold. Refolding of GS-RNase T1 was catalyzed by
      protein disulfide isomerase (PDI); substoichiometric quantities of PDI
      accelerated refolding several-fold. GS-RNase T1 refolding was inhibited by BiP;
      refolding was completely blocked in presence of a 5-fold molar excess of BiP, and
      the yield of refolding was substantially reduced by equimolar concentrations of
      BiP; the refolding was then restored by the addition of ATP. GS-RNase T1 is a
      convenient model substrate for studying protein folding linked to native
      disulfide formation in conditions comparable to those within the lumen of the
      endoplasmic reticulum.

PMID- 7626609
TI  - Malonyl-coenzyme A:acyl carrier protein acyltransferase of Streptomyces
      glaucescens: a possible link between fatty acid and polyketide biosynthesis.
AB  - Streptomyces glaucescens, a Gram-positive soil bacterium, produces the polyketide
      antibiotic tetracenomycin (Tcm) C. To study possible biochemical connections
      between the biosynthesis of bacterial fatty acids and polyketides, the abundant
      acyl carrier protein (ACP) detected throughout the growth of the tetracenomycin
      (Tcm) C-producing S. glaucescens was purified to homogeneity and found to behave
      like many other ACPs from bacteria and plants (apparent M(r) of 20,000 on gel
      filtration chromatography, apparent M(r) of 3400-4800 on sodium dodecyl sulfate
      polyacrylamide gel electrophoresis under reducing conditions, and pI
      approximately 3.8). By using an oligodeoxynucleotide synthesized in accordance
      with the sequence of residues 25-36 of the ACP, the fabC gene encoding this
      protein was cloned, and expression of this gene in Escherichia coli yielded the
      ACP entirely as the active holoenzyme. Sequence analysis of 4.3 kilobases (kb) of
      DNA flanking fabC revealed the presence of three other genes oriented in the same
      transcriptional direction in the order fabD, fabH, fabC, and fabB. Each of the
      four genes is predicted to encode proteins with high sequence similarity to the
      following components of the E. coli fatty acid synthase (FAS): the FabD malonyl
      coenzyme A:ACP acyltransferase (MAT), FabH 3-oxoacyl:ACP synthase III, AcpP ACP,
      and FabB 3-oxoacyl:ACP synthase I. Expression of the S. glaucescens fabD gene in
      E. coli produced active MAT able to catalyze in vitro the transfer of radioactive
      malonate from malonyl-coenzyme A to the E. coli AcpP and S. glaucescens FabC
      ACPs, as well as to the TcmM ACP component of the Tcm type II polyketide synthase
      [Shen, B., et al. (1992) J. Bacteriol 174, 3818-3821]. Expression of fabD also
      restored the high-temperature growth of the E. coli fabD89 mutant that bears a
      temperature-sensitive MAT. The latter finding and the close similarity between
      the organization of the S. glaucescens fabDHCB and E. coli FAS-encoding genes
      (fabH/fabD/fabG/acpP/fabF) suggest that the S. glaucescens genes encode FAS
      enzymes. Moreover, on the basis of its in vitro activity, it is possible that the
      S. glaucescens FabD MAT is responsible for charging the TcmM ACP with malonate in
      vivo, a key step in the synthesis of the deca(polyketide) precursor of Tcm C.
      This implies the existence of a functional connection between fatty acid and
      polyketide metabolism in this bacterium.

PMID- 7626610
TI  - An expanded two-state model accounts for homotropic cooperativity in biosynthetic
      threonine deaminase from Escherichia coli.
AB  - The linkage between substrate and regulatory effector binding to separate sites
      on allosteric enzymes results in shifts in their sigmoidal kinetics to regulate
      metabolism. Control of branched chain amino acid biosynthesis in Escherichia coli
      occurs in part through shifts in the sigmoidal dependence of alpha-ketobutyrate
      production promoted by isoleucine and valine binding to biosynthetic threonine
      deaminase. The structural similarity of threonine, valine, and isoleucine have
      given rise to suggestions that there may be competition among different ligands
      for the same sites on this tetrameric enzyme, resulting in a complex pattern of
      regulation. In an effort to provide a coherent interpretation of the cooperative
      association of ligands to the active sites and to the effector sites of threonine
      deaminase, binding studies using single amino acid variants were undertaken. A
      previously-isolated, feedback-resistant mutant identified in Salmonella
      typhimurium, ilvA219, has been cloned and sequenced. The phenotype is
      attributable to a single amino acid substitution in the regulatory domain of the
      enzyme in which leucine at position 447 is substituted with phenylalanine. The
      mutant exhibits hyperbolic saturation curves in both ligand binding and steady
      state kinetics. These results, in addition to calorimetric and spectroscopic
      measurements of isoleucine and valine binding, indicate that the low affinity (T)
      state is destabilized in the mutant and that it exists predominantly in the high
      affinity (R) conformation in the absence of ligands, providing an explanation for
      its resistance to isoleucine. Chemical and spectroscopic analyses of another
      mutant, in which alanine has replaced an essential lysine at position 62 that
      forms a Schiff base with pyridoxal phosphate, indicate that the cofactor is
      complexed to exogenous threonine and is therefore unable to bind additional amino
      acids at the active sites. Isoleucine and valine binding to this inactive, active
      site-saturated enzyme revealed that it too was stabilized in the R state,
      yielding binding constants in excellent agreement with the leucine to
      phenylalanine mutant. The lysine to alanine mutant was further utilized to
      demonstrate that both threonine and 2-aminobutyrate bind with stronger affinity
      to the regulatory sites than to the active sites. A direct consequence of these
      results is that substrates and analogs have a synergistic effect on the
      allosteric transition since, in effect, they act as both homotropic and
      heterotropic effectors.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7626611
TI  - Reaction of aspartate aminotransferase with L-erythro-3-hydroxyaspartate:
      involvement of Tyr70 in stabilization of the catalytic intermediates.
AB  - The reaction of Escherichia coli aspartate aminotransferase (AspAT) with L
      erythro-3-hydroxyaspartate (HOAsp) produces an intense absorption at 494 nm
      (epsilon = 13,650 M-1 cm-1), which is ascribed to the quinonoid intermediate.
      However, when Tyr70 of AspAT has been replaced by Phe, the enzyme shows only a
      faint absorption at 494 nm (epsilon = 522 M-1 cm-1) on the reaction with HOAsp.
      This indicates the involvement of the hydroxy group of Tyr70 in stabilizing the
      quinonoid intermediate formed from HOAsp and pyridoxal 5'-phosphate at the AspAT
      active site. Kinetic analysis of the absorption changes of the wild-type and Y70F
      mutant AspATs has shown that the reactions with HOAsp conform to the equation, EL
      + S<-->ES1<-->ES2<-->ES3<-->EM + P, in which there is a rapid formation of the
      quinonoid intermediate (ES2) from ES1, followed by a slow equilibrium between ES2
      and ES3. ES3 absorbs primarily at 330 nm. The kinetic parameters for individual
      steps have been determined, and free energy profiles for the reactions of the two
      enzymes with HOAsp have been obtained. The stability of the quinonoid
      intermediates of the two enzymes in the normal catalytic reactions with aspartate
      has been assessed by static measurement of the spectra in the presence of both
      aspartate and oxalacetate, and the free energy profiles for the reactions have
      been similarly obtained. Comparison of the free energy levels in the profiles
      showed that the interaction of the beta-hydroxy group of HOAsp with the hydroxy
      group of Tyr70 accounts for 8.7 kJ mol-1 of the 18.5 kJ mol-1 stabilization of
      the quinonoid intermediate by the beta-hydroxy group. Model building of the
      active site of AspAT complexed with HOAsp suggests that the rest of the
      stabilization is mediated through the interaction of the beta-hydroxy group of
      HOAsp with the protonated epsilon-amino group of Lys258. This interaction is
      expected to strengthen the hydrogen-bonding network involving Tyr70, HOAsp, and
      the coenzyme phosphate. A similar network is possibly formed in the carbinolamine
      intermediate, suggesting ES3 to be the carbinolamine. A mechanism for the
      reaction of AspAT with HOAsp, which conforms to all the kinetic and spectroscopic
      data presented here, is proposed. This study provides a basis for subsequent
      spectroscopic characterization of the HOAsp-AspAT complex, which is a good model
      for the critical intermediate (quinonoid) structure of the AspAT-catalyzed
      reactions.

PMID- 7626612
TI  - pKA values of carboxyl groups in the native and denatured states of barnase: the
      pKA values of the denatured state are on average 0.4 units lower than those of
      model compounds.
AB  - We have determined the pKA values of the 12 carboxyl residues in the native and
      denatured state of barnase by a combination of thermodynamic measurements on
      mutants of charged residues and NMR titration data. The pKA values of the 11
      residues titrating under folding conditions (above pH 2.2) were determined by two
      dimensional 1H NMR. The pKA value of the remaining residue, Asp 93 which forms a
      salt link with Arg 69 and titrates at much lower pH values, was determined by
      changes in the pH dependence of the stability of the protein upon mutation to
      Asn: pKAsp93A at low ionic strength (50 mM) and pKAsp93A at high ionic strength
      (600 mM). The overall titration of the native state is nonideal, and the protein
      retains fractionally ionized residues other than Asp 93 throughout the
      experimental pH range of 0.2-6.3. Protonation events taking place at pH values
      below 2 were further characterized by the pH dependence of the unfolding kinetics
      of wild-type and charge-mutant proteins. By comparing the observed pH dependence
      of the protein stability with that calculated from the pKA values for the native
      protein, we demonstrate that the pKA values of the denatured state are
      significantly lower than those reported for model compounds: the pKA values of
      the denatured state appear on average 0.4 units lower than previous estimates in
      the presence of chemical denaturant. The results have direct implications for
      calculations of the energetics of proton equilibria and suggest that the
      acid/thermally denatured state is not an extended coil where the residues are
      isolated from one another by the intervening solvent but is compact and involves
      intramolecular charge repulsion.

PMID- 7626613
TI  - Facile and restricted pathways for the dissociation of octenoyl-CoA from the
      medium-chain fatty acyl-CoA dehydrogenase (MCAD)-FADH2-octenoyl-CoA charge
      transfer complex: energetics and mechanism of suppression of the enzyme's oxidase
      activity.
AB  - In a previous paper, we demonstrated that the reductive half-reaction of medium
      chain fatty acyl-CoA dehydrogenase (MCAD), utilizing octanoyl-CoA as
      physiological substrate, generates two (kinetically distinct) forms of the
      reduced enzyme (MCAD-FADH2) - octenoyl-CoA charge-transfer complexes [Kumar,
      N.R., & Srivastava, D.K. (1994) Biochemistry 33, 8833-8841]. We present evidence
      that octenoyl-CoA dissociates from the second (most stable) charge-transfer
      complex (referred to as CT2) via two alternative ("facile" and "restricted")
      pathways. The dissociation of octenoyl-CoA via the facile pathway involves the
      reversal of the overall reductive half-reaction of the enzyme, generating MCAD
      FAD - octanoyl-CoA as the Michaelis complex, followed by dissociation of the
      latter complex into MCAD-FAD + octanoyl-CoA. Hence, via this pathway, octenoyl
      CoA is released from the enzyme site in the form of octanoyl-CoA. In contrast,
      the restricted pathway involves a direct (albeit slow) dissociation of octenoyl
      CoA from CT2 to yield MCAD-FADH2 + octenoyl-CoA. The kinetic profile for the
      dissociation of octenoyl-CoA via the restricted pathway matches the rate of
      oxidation of the reduced flavin (within CT2) by O2. This suggests that the
      oxidase activity of the enzyme remains suppressed as long as the reduced enzyme
      predominates in the form of the charge-transfer complex(es). The oxidase activity
      of the enzyme emerges concomitantly with the conversion of CT2 to the MCAD-FADH2 
      octenoyl-CoA Michaelis complex. The energetic basis for the dissociation of
      octenoyl-CoA via the facile and restricted pathways and the mechanism of
      suppression of the oxidase activity of the enzyme are discussed.

PMID- 7626614
TI  - Metal ion dependence of oligosaccharyl transferase: implications for catalysis.
AB  - Oligosaccharyl transferase activity exhibits an absolute requirement for certain
      divalent metal cations. Studies with reconstituted enzyme suggest a preference
      for metal ions that can adopt an octahedral coordination geometry. In order to
      gain insight into the specific role of the metal cation in catalysis, we have
      investigated the influence of the metal cofactor on catalytic turnover of the
      tripeptide substrate Bz-Asn-Leu-Thr-NHMe (1) and a closely related sulfur
      containing analog, Bz-Asn(gamma S)-Leu-Thr-NHMe (2). The metal ion substitution
      studies reveal that 1 is effectively turned over in the presence of several metal
      ions (Mn2+, Fe2+, Mg2+, and Ca2+). In contrast, 2 is only glycosylated in the
      presence of the thiophilic metal cations manganese and iron. When the enzyme is
      reconstituted with the oxophilic cations magnesium and calcium, 2 shows minimal
      substrate behavior. With the amide substrate 1, the distinct preference for
      manganese over magnesium may argue against direct coordination of the metal to
      the lipid-linked substrate pyrophosphate moiety. This fact, together with the
      comparative studies with asparagine- and thioasparagine-containing tripeptides,
      implicates the metal cofactor in a role that places it proximal to the peptide
      binding site.

PMID- 7626615
TI  - Characterization of the interaction between PQQ and heme c in the
      quinohemoprotein ethanol dehydrogenase from Comamonas testosteroni.
AB  - Quinohemoprotein ethanol dehydrogenase from Comamonas testosteroni (QH-EDH)
      contains two cofactors, 2,7,9-tricarboxy-1H-pyrrolo[2,3-f]quinoline-4,5-dione
      (PQQ) and heme c. Since previous studies on the kinetics of this enzyme suggested
      that both participate in electron transfer, spectroscopic investigations were
      performed of the oxidized and reduced holo- and apoenzyme (without PQQ but with
      heme c) to reveal the nature of the interaction between the two redox centers.
      From this it appears that the properties of the heme in the enzyme are affected
      by the presence of PQQ, as judged from the shift of the maxima in the
      ultraviolet/visible absorption spectra of the heme moiety in both reduced and
      oxidized QH-EDH and the 60-mV increase of the heme midpoint redox potential
      caused by PQQ addition. Also 1H-NMR spectroscopy was indicative for interaction
      since binding of PQQ induced shifts in the resonances of the methyl groups of the
      porphyrin ring in the oxidized form of the apoenzyme and a shift in the
      methionine heme ligand resonance of the reduced form of the apoenzyme. On the
      other hand, resonance Raman spectra of the heme in the different enzyme forms
      were nearly similar. These results suggest that a major effect of PQQ binding to
      apo-QH-EDH is a rotation of the methionine ligand of heme c. Since no
      intermediate 1H-NMR spectra were observed upon titration of apoenzyme with PQQ,
      apparently no exchange occurs of PQQ between (oxidized) holo- and apoenzyme at
      the NMR time scale and at that of the experiment.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7626616
TI  - Monovalent cations affect dynamic and functional properties of the tryptophan
      synthase alpha 2 beta 2 complex.
AB  - Monovalent cations affect both conformational and catalytic properties of the
      tryptophan synthase alpha 2 beta 2 complex from Salmonella typhimurium. Their
      influence on the dynamic properties of the enzyme was probed by monitoring the
      phosphorescence decay of the unique Trp-177 beta, a residue located near the beta
      active site, at the interface between alpha- and beta-subunits. In the presence
      of either Li+, Na+, Cs+, or NH4+, the phosphorescence decay is biphasic and the
      average lifetime increases indicating a decrease in the flexibility of the N
      terminal domain of the beta-subunit. Since amplitudes but not lifetimes are
      affected, cations appear to shift the equilibrium between preexisting enzyme
      conformations. The effect on the reaction between indole and L-serine was studied
      by steady state kinetic methods at room temperature. We found that cations: (i)
      bind to the L-serine--enzyme derivatives with an apparent dissociation constant,
      measured as the concentration of cation corresponding to one-half of the maximal
      activity, that is in the millimolar range and decreases with ion size; (ii)
      increase kcat with the order of efficacy Cs+ > K+ > Li+ > Na+; (iii) decrease KM
      for indole, Na+ being the most effective and causing a 30-fold decrease; and (iv)
      cause an increase of the kcat/KM ratio by 20-40-fold. The influence on the
      equilibrium distribution between the external aldimine and the alpha
      aminoacrylate, intermediates in the reaction of L-serine with the beta-subunits
      of the enzyme, was found to be cation-specific.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7626617
TI  - Monovalent metal ions play an essential role in catalysis and intersubunit
      communication in the tryptophan synthase bienzyme complex.
AB  - This investigation shows that the alpha 2 beta 2 tryptophan synthase bienzyme
      complex from Salmonella typhimurium is subject to monovalent metal ion
      activation. The effects of the monovalent metal ions Na+ and K+ were investigated
      using rapid scanning stopped-flow (RSSF), single-wavelength stopped-flow (SWSF),
      and steady-state techniques. RSSF measurements of individual steps in the
      reaction of L-serine and indole to give L-trytophan (the beta-reaction) as well
      as the reaction of 3-indole-D-glycerol 3'-phosphate (IGP) with L-serine (the
      alpha beta-reaction) demonstrate that monovalent metal ions such as Na+ and K+
      change the distribution of intermediates in both the transient and steady states.
      Therefore the metal ion effect alters relative ground-state energies and the
      relative positions of ground- and transition-state energies. The RSSF spectra and
      SWSF time courses show that the turnover of indole is significantly reduced in
      the absence of either Na+ or K+. The alpha-aminoacrylate Schiff base species, E(A
      A), is in a less active state in the absence of monovalent metal ions. Na+
      decreases the steady-state rate of IGP cleavage (the alpha-reaction) to about 30%
      of the value obtained in the absence of metal ions. Steady-state investigations
      show that in the absence of monovalent metal ions the alpha- and alpha beta
      reactions have the same activity. Na+ binding gives a 30-fold stimulation of the
      alpha-reaction when the beta-site is in the E(A-A) form.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7626618
TI  - Mass spectrometric analysis of 21 phosphorylation sites in the internal repeat of
      rat profilaggrin, precursor of an intermediate filament associated protein.
AB  - Profilaggrin, a highly phosphorylated protein synthesized in mammalian cornified
      epithelia, is the precursor of filaggrin, a protein that is involved in
      aggregation of keratin during terminal differentiation. Possible functions for
      the phosphorylation include preventing premature aggregation of keratin, packing
      profilaggrin into a storage granule, association of other proteins with the
      granule, and/or regulating proteolytic processing of profilaggrin. As a first
      step in characterizing the phosphorylation of rat profilaggrin, tryptic peptides
      of filaggrin and profilaggrin were fractionated by reverse-phase HPLC and
      analyzed by ionspray mass spectrometry. Nine putative phosphopeptides were
      identified as those with masses 80 Da (or multiples of 80 Da) greater than the
      predicted unphosphorylated masses. The six that were phosphorylated to a high
      stoichiometry were analyzed further. Several multiply phosphorylated peptides
      underwent neutral loss of H3PO4 during collisional activation, complicating
      interpretation of the MS/MS spectra. In order to circumvent this problem, an
      alternative strategy was applied in which peptide mixtures were treated with
      Ba(OH)2, resulting in beta-elimination of H3PO4 and generation of dehydrated
      serine or threonine at the site of phosphorylation. Peptides containing
      dehydrated serine or threonine fragmented well, providing unequivocal
      identification of multiple phosphorylation sites in peptides as long as 39 amino
      acids. The phosphopeptides (with phosphorylated residues underlined) were
      GQQHSGHPQVYYYGVEETEDESDAQQGHHQQQQQQR, GGQAGSHSESEASGGQAGR, HTSRPEQSPDTAGR,
      GESPAGQQSPDR, EASASQSSDSEGHSGAHAGIGQGQTSTTHR, and
      GSSESQASDSEGHSDYSEAHTQGAHGGIQTSSQR.

PMID- 7626620
TI  - Topological disposition of lysine 943 in native Na+/K(+)-transporting ATPase.
AB  - Because of the conflicting conclusions that have been reached regarding the
      location of the two putative membrane-spanning segments from cysteine 911 through
      isoleucine 929 and from isoleucine 946 through cysteine 964 in the alpha subunit
      of native ovine Na+/K(+)-transporting ATPase, the disposition of lysine 943 with
      respect to the plane of the lipid bilayer was investigated. Sealed, right-side
      out vesicles were modified with pyridoxal phosphate and Na[3H]BH4 in the presence
      and absence of saponin, a reagent that creates holes in the membranes. Modified
      alpha polypeptide was isolated, and digested with trypsin and chymotrypsin to
      release the desired peptides, QQGMK and QQGMK([3H]pyr)NK (where [3H]pyr
      designates the modification on lysine 943). These peptides, after cyclization of
      their amino-terminal glutamines, were isolated with an immunoadsorbent specific
      for the amino-terminal sequence pyroglutamyl-QGM-followed by high-pressure liquid
      chromatography on a C-18 reverse phase column. Comparisons were made of the
      extent of incorporation of radioactivity into lysine 943 between sealed vesicles
      and sealed vesicles pretreated with saponin. An increase in incorporation into
      lysine 943 of 5-fold to 18-fold was seen in vesicles pretreated with saponin
      prior to the modification with pyridoxal phosphate. This increase in
      incorporation is consistent with a cytoplasmic location for lysine 943. This
      conclusion places the residues on the carboxy-terminal side of the putative
      membrane-spanning segment from cysteine 911 through isoleucine 929 and the amino
      terminal side of the putative membrane-spanning segment from isoleucine 946
      through cysteine 964 in the ovine alpha subunit on the cytoplasmic side of the
      membrane.

PMID- 7626619
TI  - Production and properties of skeletal myosin subfragment 1 selectively labeled
      with fluorescein at lysine-553 proximal to the strong actin-binding site.
AB  - We describe, for the first time, the reaction of skeletal myosin subfragment 1 (S
      1) with the succinimido ester of 6-[fluorescein-5(and 6)-carboxamido]hexanoic
      acid (FHS), which takes place at pH 7.0, 20 degrees C, within a 15 min period, in
      the presence of 1.5-1.8-fold molar excess of reagent over protein. As a result,
      0.9-1.0 mol of fluorescyl group/mol of S-1 was covalently incorporated
      exclusively into the 95 kDa heavy chain as monitored by spectroscopic
      measurements. The central 50 kDa segment included the main site of fluorescence
      attachment as assessed by gel electrophoresis. The extent of S-1--FHS conjugation
      is strongly sensitive to F-actin binding but not to the interaction of
      nucleotides. The formation of the rigor F-actin--S-1 complex decreased the level
      of S-1 labeling to 20% without any competition between actin and S-1 for FHS
      binding. The derivatization of S-1 did not alter the K(+)-ATPase activity, but it
      enhanced the Ca(2+)-ATPase and Mg(2+)-ATPase to 150% and 225%, respectively,
      whereas it lowered the actin-activated ATPase to only 75% of the original
      activity. A double-reciprocal plot of the ATPase rate against actin concentration
      indicated a 2-fold decrease of the Vmax value for modified S-1, while the Km for
      actin was unchanged. Cosedimentation experiments did not reveal disruption of the
      rigor acto-S-1 interaction by the bound fluorophore. The labeled S-1 heavy chain
      was isolated, and its total tryptic digest was fractionated by reverse-phase
      HPLC.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7626621
TI  - Thermodynamics of interaction of the fusion-inhibiting peptide Z-D-Phe-L-Phe-Gly
      with dioleoylphosphatidylcholine vesicles: direct calorimetric determination.
AB  - The binding of the fusion-inhibiting peptide Z-D-Phe-L-Phe-Gly to unilamellar
      lipid vesicles of dioleoylphosphatidylcholine (DOPC) was investigated by
      isothermal titration calorimetry (ITC). The peptide Z-D-Phe-L-Phe-Gly is known to
      inhibit fusion of myxo- and paramyxoviruses with cells as well as cell-cell and
      vesicle-vesicle fusion in model systems. Calorimetric titrations conducted over a
      range of temperatures permitted characterization of the thermodynamics of the
      interaction of Z-D-Phe-L-Phe-Gly with model DOPC lipid membranes. Simultaneous
      global analysis of 15 ITC binding curves acquired at four different temperatures
      allowed determination of the equilibrium site association constant (K),
      stoichiometry of binding (n), binding enthalpy change (delta H), and heat
      capacity change of binding (delta Cp) in a single set of experiments. The binding
      affinity and enthalpy change per mole of DOPC bound at 25 degrees C was log K =
      2.463 +/- 0.075 and delta H = -1.07 +/- 0.12 kcal/mol DOPC while the binding heat
      capacity change per mole of DOPC bound was delta Cp = -20.3 +/- 2.8 cal/(K.mol
      DOPC) with a temperature dependence (from 10-45 degrees C) of d(delta Cp)/dT =
      0.37 +/- 0.18 cal/(K2.mol DOPC). A temperature-independent binding stoichiometry
      was determined to be n = 5.56 +/- 0.33 DOPC molecules per Z-D-Phe-L-Phe-Gly. A
      comparison of these results with previous peptide-lipid binding studies is
      discussed as is their relevance to a current model of the interaction of fusion
      inhibiting peptides with phospholipid membranes.

PMID- 7626622
TI  - Mutagenesis at a highly conserved tyrosine in monoamine oxidase B affects FAD
      incorporation and catalytic activity.
AB  - Monoamine oxidase B (MAO B), an integral protein of the outer mitochondrial
      membrane, catalyzes the oxidative deamination of various neuroactive and
      vasoactive amines. A covalently bound FAD cofactor at Cys-397 of human MAO B is
      required for the oxidation of the amine substrates. In addition to the covalent
      binding site, MAO B also contains a noncovalent FAD binding region (residues 6
      34) known as the dinucleotide binding motif. Previously, we have shown that Glu
      34 is required for catalytic activity, presumably by forming a hydrogen bond
      between the carboxylate group of glutamate and the 2'-hydroxyl group of ribose in
      the AMP moiety of FAD. In this work, we have identified a third FAD binding site
      in MAO B (residues 39-46) by sequence comparisons to other flavoenzymes. The
      conserved sequence contains a tyrosine residue (Tyr-44) which, based on the X-ray
      crystal structure of ferredoxin-NADP+ reductase, is postulated to participate in
      FAD binding through van der Waals contact with the isoalloxazine ring and a
      hydrogen bond to the 3'-hydroxy of the ribityl moiety. To test the postulated
      role of this tyrosine residue, site-directed mutants that encode substitutions at
      Tyr-44 were prepared and expressed in mammalian COS-7 cells. Variant MAO B
      enzymes were then characterized with respect to enzymatic activity and [14C]FAD
      incorporation. Substitution of tyrosine with phenylalanine had no effect on MAO B
      activity or the level of [14C]FAD incorporation compared to the wild-type enzyme,
      indicating that the hydroxyl group of the tyrosine residue was not essential at
      residue 44.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7626623
TI  - Binding of cephalothin and cefotaxime to D-ala-D-ala-peptidase reveals a
      functional basis of a natural mutation in a low-affinity penicillin-binding
      protein and in extended-spectrum beta-lactamases.
AB  - Two clinically-important beta-lactam antibiotics, cephalothin and cefotaxime,
      have been observed by X-ray crystallography bound to the reactive Ser62 of the D
      alanyl-D-alanine carboxypeptidase/transpeptidase of Streptomyces sp. R61.
      Refinement of the two crystal structures produced R factors for 3 sigma (F) data
      of 0.166 (to 1.8 A) and 0.170 (to 2.0 A) for the cephalothin and cefotaxime
      complexes, respectively. In each complex, a water molecule is within 3.1 and 3.6
      A of the acylated beta-lactam carbonyl carbon atom, but is poorly activated by
      active site residues for nucleophilic attack and deacylation. This apparent lack
      of good stereochemistry for facile hydrolysis is in accord with the long half
      lives of cephalosporin intermediates in solution (20-40 h) and the efficacy of
      these beta-lactams as inhibitors of bacterial cell wall synthesis. Different
      hydrogen binding patterns of the two cephalosporins to Thr301 are consistent with
      the low cefotaxime affinity of an altered penicillin-binding protein, PBP-2x,
      reported in cefotaxime-resistant strains of Streptococcus pneumoniae, and with
      the ability of mutant class A beta-lactamases to hydrolyze third-generation
      cephalosporins.

PMID- 7626624
TI  - Multi-site-specificity of the vitamin K-dependent carboxylase: in vitro
      carboxylation of des-gamma-carboxylated bone Gla protein and Des-gamma
      carboxylated pro bone Gla protein.
AB  - The vitamin K-dependent carboxylase processes multiple glutamic acid residues to
      gamma-carboxyglutamic acid (Gla) residues in a limited number of proteins. The
      targeted proteins are synthesized with an amino-terminal propeptide which has
      been shown to play an important role in gamma-carboxylation. The specificity of
      the enzyme for each potential Gla site, the direction of carboxylation, and the
      influence of a bound propeptide on these events are not understood. Des-gamma
      carboxy forms of bone Gla protein (BGP), which contain potential Gla residues at
      positions 17, 21, and 24, were employed as model substrates to determine the
      multi-site-specificity of the enzyme. Recombinant bovine des-gamma-carboxylated
      proBGP (rdproBGP) and heat-decarboxylated BGP (dBGP), lacking a propeptide, were
      used as substrates for a bovine liver carboxylase, and the in vitro reaction
      products were analyzed for the formation of 14CO2 Gla. The di-Gla species was
      found to be the predominant product of in vitro carboxylation of both rdproBGP
      and dBGP at less than saturating concentrations of each substrate. Carboxylation
      of both substrates occurred preferentially at the more C-terminal potential Gla
      sites, residues 21 and 24. A similar pattern of carboxylation was observed with a
      rat bone cell carboxylase, suggesting no species or tissue variation in the
      enzyme specificity. Some tricarboxylated product accumulated during carboxylation
      of rdproBGP but not dBGP, suggesting that the covalently bound propeptide directs
      more complete carboxylation of the Gla domain. In addition, monocarboxylated
      rdproBGP was found to accumulate in the absence but not in the presence of a free
      noncovalently attached propeptide, indicating that free propeptide affects more
      efficient carboxylation of rdproBGP.

PMID- 7626625
TI  - Core domain of hirudin from the leech Hirudinaria manillensis: chemical
      synthesis, purification, and characterization of a Trp3 analog of fragment 1-47.
AB  - Hirudin is a small (approximately 7 kDa) disulfide-cross-linked polypeptide known
      as the most potent and specific thrombin inhibitor. We have previously shown that
      the N-terminal proteolytic fragment 1-47 of hirudin HM2 from Hirudinaria
      manillensis maintains inhibitory action toward thrombin [Vindigni, A., et al.
      (1994) Eur. J. Biochem. 226, 323-333]. Here we report the solid-phase chemical
      synthesis of an analog of fragment 1-47 bearing a Tyr3-->Trp exchange (Y3W
      analog). The crude, reduced peptide was purified by reverse-phase HPLC and
      subjected to oxidative folding to the disulfide-cross-linked species. The folding
      process of the Y3W analog was slower than that of the natural fragment 1-47, but
      nevertheless still occurred almost quantitatively as the natural species. The
      overall final yield of the synthetic product was approximately 35%, and its
      identity and homogeneity was established by a number of analytical techniques,
      including electrospray mass spectometry. The unique alignment of the three
      disulfide bridges of the Y3W analog was established by peptide mapping as Cys6
      Cys14, Cys16-Cys28, and Cys22-Cys37 and shown to be identical to that of the
      natural fragment. The results of far- and near-ultraviolet circular dichroism and
      fluorescence emission measurements provided evidence that the Y3W analog retains
      the structural features of the natural species. The thermodynamic quantities
      (delta GD, delta Hm, delta Sm, and delta Cp) characterizing the reversible and
      cooperative thermal unfolding processes of the Y3W analog (Tm = 60.5 degrees C)
      and the natural fragment species (Tm = 62.5 degrees C) were evaluated. Despite
      the relatively high Tm values, the stability of both fragment species at 37
      degrees C was only approximately 10 kJ mol-1, well below the average 50 kJ mol-1
      typical of single-domain globular proteins. The synthetic Y3W species was found
      to be approximately 5-fold more active (KI = 30 +/- 5 nM) than the natural
      fragment 1-47 (KI = 150 +/- 20 nM) in inhibiting thrombin. Of interest was that
      the difference in the free energies of binding to thrombin at 37 degrees C, delta
      delta Gb, between the Y3W analog and natural species (4.2 kJ mol-1) was that
      expected for the difference in hydrophobicity between the two polypeptides
      resulting from the Tyr-->Trp exchange. The results of this study indicate that
      solid-phase chemical synthesis represents a convenient and high-yield procedure
      to prepare analogs of the biologically active, N-terminal core domain of hirudin
      with improved functional properties.

PMID- 7626626
TI  - Aggregation-dependent signaling in human platelets is sensitive to protein
      serine/threonine phosphatase inhibitors.
AB  - When platelets are stimulated by the addition of thrombin, a series of temporally
      linked signaling events are initiated. Some of the early events are needed to
      engage the integrin glycoprotein (GP) IIb-IIIa in a high-affinity state. This in
      turn leads to aggregation, which initiates a wave of events distinct from those
      triggered by thrombin. Platelet responses are sensitive to protein
      serine/threonine phosphatase inhibitors, but which events are dependent on
      protein phosphatase activity is not known. In the present studies, the effect of
      the phosphatase inhibitor calyculin A on aggregation-induced signaling was
      examined. The addition of 0.2 unit/mL thrombin caused aggregation-dependent
      redistribution of cytoskeletal proteins (actin binding protein, talin, vinculin,
      and alpha-actinin), glycoproteins (GPIIb-IIIa, PECAM), and signaling molecules
      (PI3-kinase, pp60c-src) to the cytoskeletal fraction of platelets. Addition of 1
      2 microM calyculin A blocked the ability of 0.2 unit/mL thrombin to induce
      aggregation and the association of these molecules with the cytoskeleton.
      Aggregation (60-80% of control) was restored if 1 unit/mL thrombin was added, but
      there was no corresponding redistribution of actin binding protein, talin,
      vinculin, alpha-actinin, GPIIb-IIIa, PECAM, PI3-kinase, and pp60c-src to the
      cytoskeleton. Treatment of platelets with calyculin A resulted in an increase in
      the phosphorylation state of a membrane skeletal protein of 50 kDa. These data
      strongly suggest that platelet aggregation is dissociable from aggregation
      induced signaling, which is dependent on type 1 and 2A phosphatase activities.

PMID- 7626627
TI  - Identification of apolipoprotein B100 polymorphisms that affect low-density
      lipoprotein metabolism: description of a new approach involving monoclonal
      antibodies and dynamic light scattering.
AB  - Rare mutations in apolipoprotein B (apoB) can cause defective binding of low
      density lipoproteins (LDLs) to the LDL receptor, leading to elevated plasma
      cholesterol levels and premature atherosclerosis. This communication describes a
      novel approach to study the effects of apoB mutations on LDL metabolism.
      Monoclonal antibody MB19 identifies a common polymorphism in apoB, an Ile/Thr
      substitution at residue 71, by binding with a 60-fold higher affinity to
      apoB(Ile71)-containing LDL. Because each LDL contains a single apoB, a maximum of
      two LDLs may be bound by the bivalent monoclonal antibody. Thus, at the
      appropriate concentration, an equivalent amount of MB19 will promote substantial
      dimer formation of LDL containing the strongly binding apoB(Ile71), but little
      dimer formation of LDL containing the weakly binding apoB(Thr71). For LDL
      isolated from heterozygous individuals, the amount of dimer formed, determined by
      dynamic light scattering, yields an estimate of the allelic ratio of the two
      forms of LDL. For such individuals, not only the effect of the polymorphism
      recognized by MB19 but also the effects of other polymorphisms on the LDL allelic
      ratio can be determined. Examination of six normolipemic MB19 heterozygotes gave
      percent allelic ratios between 48:52 and 51:49 tight:weak-binding LDL, not
      significantly different from a 50:50 ratio. These individuals were also
      heterozygous for six common apoB polymorphisms, allowing calculation of the odds
      that each of these polymorphisms caused significant alterations in lipid levels.
      In contrast, the rare mutation at residue 3500 causing defective binding to the
      LDL receptor and familial defective apoB100 (FDB) resulted in substantial changes
      (26:74 and 13:87) in LDL allelic ratio in both of two FDB individuals examined.

PMID- 7626628
TI  - Contributions of individual kringle domains toward maintenance of the chloride
      induced tight conformation of human glutamic acid-1 plasminogen.
AB  - The roles of each of the three omega-amino acid-binding kringles (K) of Glu1-Pg,
      viz., [K1Pg], [K4Pg], and [K5Pg], in engendering the Cl(-)-induced alteration to
      its tight (T) conformation and in effecting the epsilon-aminocaproic acid (EACA)
      mediated change to the relaxed (R) protein conformation have been investigated by
      mutagenesis strategies wherein the omega-amino acid ligand-binding energies in
      the individual kringles in recombinant (r)-Glu1-Pg were greatly reduced. This was
      accomplished in the most conservative manner possible by altering a critical Asp
      residue in each relevant kringle to Asn. The particular mutations chosen were r
      [D139N]Glu1-Pg, r-[D413N]Glu1-Pg, and r-[D518N]Glu1-Pg, in which a conserved Asp
      residue at a homologous sequence position in each of the three kringle domains is
      eliminated. These changes also lead to a great reduction of the EACA-binding
      strength of [K1Pg], [K4Pg], and [K5Pg], respectively. The s0(20,w) of wild-type
      (wt) r-Glu1-Pg in the presence of levels of Cl(-)-sufficient to fully occupy its
      binding sites on this protein was 5.9 S, a value reduced to 4.9 S as a result of
      addition of saturating concentrations of EACA to the Cl-/Glu1-Pg complex. Neither
      Cl- nor EACA substantially altered the s0(20,w) value of 5.2 S for r-[D139N]Glu1
      Pg (4.8 S) or r-[D413N]Glu1-Pg (4.5 S). On the other hand, the s0(20,w) value of
      5.2 S for r-[D518N]Glu1-Pg at saturating levels of Cl- is slightly reduced to 4.8
      S upon addition of binding maximal concentrations of EACA.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7626629
TI  - Mutations at positions 13 and/or 914 in Escherichia coli 16S ribosomal RNA
      interfere with the initiation of protein synthesis.
AB  - Mutations at positions 13 (U-->A) and/or 914 (A-->U) of Escherichia coli 16S rRNA
      severely affect cell growth and protein synthesis, when expressed in vivo in a
      vector encoding an rrn operon under control of an inducible promoter. In vitro
      assays using extension inhibition indicate that the mutations interfere with the
      formation of the 30S translational initiation complex, which can account for
      their effect on cell growth. The two mutations destabilize an adjacent pseudoknot
      helix in which bases 17-19 pair to bases 916-918. This was shown by the increased
      binding of an oligodeoxyribonucleotide probe complementary to one strand of the
      pseudoknot helix, and by the increased reactivity to kethoxal of base G917 within
      this helix. These observations suggest that this pseudoknot helix participates in
      the formation of the 30S translational initiation complex.

PMID- 7626630
TI  - Stable photobleaching of P840 in Chlorobium reaction center preparations:
      presence of the 42-kDa bacteriochlorophyll a protein and a 17-kDa polypeptide.
AB  - Simple procedures for the anaerobic preparation of photoactive and stable P840
      reaction centers from Chlorobium tepidum and Chlorobium limicola in good yield
      are presented and quantitated. The subunit composition was tested by
      cosedimentation in sucrose density gradients. For C. limicola, it minimally
      comprises four subunits: the P840 reaction center protein PscA, the BChla antenna
      protein FMO, the FeS protein PscB with centers A and B, and a positively charged
      17-kDa protein denoted PscD. The preparation from Chlorobium tepidum additionally
      contained PscC, a cytochrome c-551. The BChla absorption peak of the purified
      complexes was at 810 nm, with a shoulder at 835 nm. The ratio of the shoulder to
      the peak was 0.25, which corresponds to 1 reaction center per 70 BChla molecules
      if a uniform extinction coefficient of BChla is assumed. However, bleaching at
      610 nm in continuous light corresponded up to 1 photoactive reaction center per
      50 BChla molecules. Therefore, either the extinction coefficient of BChla in the
      reaction center is overestimated or the one for photobleaching is underestimated.
      In any case, the major portion of the reaction center was photoactive in the
      preparations. A P840 reaction center subcomplex, lacking PscD and deficient in
      FMO and PscB, but retaining the cytochrome c subunit, was obtained as a side
      product. It was photoinactive and had an absorption peak at 814 nm and a 835/814
      absorbance ratio of 0.42. FMO and PscB show the tendency to form a complementary
      subcomplex. FMO and PscD are apparently required to stabilize the photoactive
      reaction center, while the cytochrome c subunit is not.

PMID- 7626631
TI  - Comparison of psbO and psbH deletion mutants of Synechocystis PCC 6803 indicates
      that degradation of D1 protein is regulated by the QB site and dependent on
      protein synthesis.
AB  - Mutants of the cyanobacterium Synechocystis PCC 6803 lacking the psbO or psbH
      gene are more vulnerable to photoinhibition than the wild type (WT). In the case
      of the psbO-less mutant, the increased sensitivity to photodamage is also
      accompanied by accelerated turnover of the D1 protein and a rapid rate of
      recovery on transfer to non-photoinhibitory conditions. In contrast, in low light
      the psbH-less mutant has a poor ability to recover after photoinhibition and has
      a reduced rate of D1 turnover as compared with WT. Since the psbO gene encodes
      the 33 kDa manganese-stabilizing protein associated with the water-splitting
      reaction, the increased sensitivity to photoinduced damage is attributed to
      perturbation of electron transfer processes on the donor side of photosystem II
      (PSII). In contrast, the absence of H protein, encoded by the psbH gene, affects
      the acceptor side of PSII with preferential photoinhibitory damage occurring at
      the QB site. The apparent consequence of this is that the psbH-less mutant,
      unlike the psbO-less mutant, is not able to regulate the rate of turnover of the
      D1 protein. In all cases it was shown that chloramphenicol, which blocks protein
      synthesis, enhances the rate of photoinhibition as judged by a decrease in oxygen
      evolution but slows down the rate of degradation of D1 protein compared to that
      observed during normal turnover.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7626632
TI  - Conformation of A82846B, a glycopeptide antibiotic, complexed with its cell wall
      fragment: an asymmetric homodimer determined using NMR spectroscopy.
AB  - Proton NMR assignments were determined for the asymmetric dimer complex of
      A82846B with the pentapeptide cell-wall fragment. A total of 683 experimental
      constraints, both distance and dihedral, were collected from NOESY and COSY data
      sets. From these constraints, a total of 80 structures were calculated using
      standard X-PLOR protocols. These structures were subsequently refined using the
      full CHARMm potential and the addition of water molecules in the calculation. The
      CHARMm structures occupied more conformational space than did the X-PLOR
      structures and were utilized for the structure analysis. From the structures, a
      unique set of interactions for the dALA-5 carboxylate pocket was observed, having
      backbone amides from residues 2 and 3 hydrogen bonding one carboxylate oxygen
      while amide 4 and the side chain amide from Asn-3 hydrogen bond the other oxygen.
      Also, near the N-terminal region of the ligand, the GGLU-2's carboxylate forms a
      hydrogen bond with the asymmetric disaccharide dyad, which helps to define the
      interactions seen for this part of the ligand.

PMID- 7626633
TI  - Structure and dynamics of interstrand guanine association in quadruplex telomeric
      DNA.
AB  - Exchanges of the amino and imino protons in guanine quartets of telomeric DNA
      have been time-resolved by laser Raman spectroscopy. The Raman dynamic probe has
      been applied to parallel and antiparallel quadruplexes formed by the telomeric
      repeat of Oxytricha nova, d(T4G4)4, and to the highly thermostable parallel
      quadruplex formed by d(G12). Time-dependent Raman spectra of the d(G12)
      quadruplex reveal two characteristic exchange reactions for guanine N2 amino
      groups. At 10 degrees C, the pseudo-first-order exchange rates are kN2H(10
      degrees C) = 5.7 x 10(-3) and k'N2H'(10 degrees C) = 1.2 x 10(-2) min-1,
      assignable to Hoogsteen-hydrogen-bonded and non-hydrogen-bonded N2 protons,
      respectively. These measurements provide the first quantitative determination of
      two kinetically distinct N2 amino proton exchange reactions in the guanine
      quartet and demonstrate that amino group rotation about the C2-N2 bond is highly
      restricted in the quadruplex. No exchange of guanine N1 imino sites occurs in
      d(G12) at 10 degrees C, and N1 exchange remains slow even at 95 degrees C
      [kN1H(95 degrees C) = 2.7 x 10(-2) min-1], indicating severe suppression of imino
      exchange in guanine quartets. For both parallel and antiparallel quadruplexes of
      d(T4G4)4, proton exchange rates decrease in the order thymine N3 imino > guanine
      N2 amino > guanine N1 imino. The rapid exchange of thymine N3 imino sites
      indicates that thymine quartets are not stabilized in Oxytricha quadruplexes. The
      protium-->deuterium exchange experiments also establish new guanine Raman band
      assignments. Importantly, the 1603 cm-1 band is due to in-plane bending of N1-H,
      while the 1644 cm-1 band involves scissoring of the N2 amino group. Accordingly,
      the 1603 and 1644 cm-1 bands are potentially valuable markers of hydrogen-bonding
      interactions specific to guanine imino and amino sites, respectively. The present
      findings also show that guanine hydrogen bonding and exchange dynamics are not
      interrelated in a simple manner. Despite extraordinary retardation of N1 imino
      proton exchange, Raman markers suggest that Hoogsteen-type guanine-guanine
      hydrogen bonding (N1-H...O=C6) is comparable in strength to hydrogen bonding of
      N1-H with water and, surprisingly, much weaker than hydrogen bonding between N1-H
      and the cytosine N3 acceptor of Watson-Crick B DNA.

PMID- 7626634
TI  - On the thermal stability of alpha-crystallin: a new insight from infrared
      spectroscopy.
AB  - alpha-Crystallin is a major structural protein of the vertebrate lens which shows
      structural and functional similarities to small heat shock proteins. The
      structure and the thermal stability of bovine alpha-crystallin were studied by
      Fourier-transform infrared spectroscopy, circular dichroism, and differential
      scanning calorimetry. Infrared spectroscopic data provide evidence which
      corroborates the view that the secondary structure of alpha-crystallin is highly
      ordered and consists predominantly of beta-sheets. However, the present results
      fail to support the widespread notion of an extremely high thermal stability of
      the protein. All three experimental approaches used in this study show that alpha
      crystallin undergoes a major thermotropic transition with a midpoint at 60-62
      degrees C. Furthermore, Fourier-transform infrared spectra provide evidence that
      this conformational transition is associated with a massive loss of the native
      beta-sheet structure. These results shed new light on structural properties of
      alpha-crystallin and have important implications for understanding the mechanism
      of the chaperone-like action of this protein.

PMID- 7626635
TI  - Crystal structure of a D-amino acid aminotransferase: how the protein controls
      stereoselectivity.
AB  - The three-dimensional structure of D-amino acid aminotransferase (D-AAT) in the
      pyridoxamine phosphate form has been determined crystallographically. The fold of
      this pyridoxal phosphate (PLP)-containing enzyme is completely different from
      those of any of the other enzymes that utilize PLP as part of their mechanism and
      whose structures are known. However, there are some striking similarities between
      the active sites of D-AAT and the corresponding enzyme that transaminates L-amino
      acids, L-aspartate aminotransferase. These similarities represent convergent
      evolution to a common solution of the problem of enforcing transamination
      chemistry on the PLP cofactor. Implications of these similarities are discussed
      in terms of their possible roles in the stabilization of intermediates of a
      transamination reaction. In addition, sequence similarity between D-AAT and
      branched chain L-amino acid aminotransferase suggests that this latter enzyme
      will also have a fold similar to that of D-AAT.

PMID- 7626637
TI  - Substrate-based inhibitors of lanosterol 14 alpha-methyl demethylase: II. Time
      dependent enzyme inactivation by selected oxylanosterol analogs.
AB  - Selected 15-, 32-, and 15,32-substituted lanosterol analogs are shown here to
      display time-dependent inactivation and lanosterol 14 alpha-methyl demethylase.
      These molecules are competitive with respect to substrate and require NADPH and
      O2 in order to display time dependence, thus supporting the premise that they are
      mechanism-based inactivators. Structural features required for lanosterol
      demethylation by the lanosterol demethylase such as nuclear double bond location
      and availability of an abstractable 15 alpha-proton are also essential elements
      for time-dependent inactivation. 32-(S)-Vinyllanost-8-en-3 beta,32-diol is a
      potent time-dependent inactivator (Kinact/Ki = 0.36 min-1 microM-1), while the 32
      (R)-vinyllanost-8-en-3 beta,32-diol functions solely as a competitive demethylase
      inhibitor. These results support the premise that stereoselective oxidation
      occurs during lanosterol demethylation and that the 32-pro-S proton is abstracted
      during the demethylation reaction.

PMID- 7626636
TI  - Substrate-based inhibitors of lanosterol 14 alpha-methyl demethylase: I.
      Assessment of inhibitor structure-activity relationship and cholesterol
      biosynthesis inhibition properties.
AB  - A series of 15-, 32-, and 15,32-substituted lanost-8-en-3 beta-ols is described
      which function as inhibitors of cholesterol biosynthesis. These agents inhibit
      lanosterol 14 alpha-methyl demethylase activity as well as suppress HMG-CoA
      reduction activity in cultured cells. Several of these agents are extremely
      potent as both demethylase inhibitors and reductase suppressors, while others are
      more selective in their activities. Selected regio double bond isomers show
      preference for demethylase inhibition with the following order: delta 8 > delta 7
      > delta 6 = unsaturated sterols. Comparisons also show that 4,4-dimethyl sterols
      are always more potent demethylase inhibitors and reductase suppressors than
      their 4,4-bisnomethyl counterparts. However, evaluation of an extensive
      oxylanosterol series leads us to conclude that demethylase inhibition and
      reductase suppression are not parallel in the same molecule. In addition, the
      oxylanosterols, but not the oxycholesterols, are able to disrupt coordinate
      regulation of HMG-CoA reductase from the LDL receptor. Thus, oxylanosterol
      treatment at levels which suppress reductase activity enhances LDL receptor
      activity. These results demonstrate that compounds can be made which (1) are
      selective reductase suppressors enabling dissection of the dual inhibitor nature
      of these compounds and (2) maximize reductase suppression and LDL receptor
      induction without demethylase inhibition which could lead to novel agents for
      serum cholesterol lowering.

PMID- 7626638
TI  - Molecular dynamics simulation of cytochrome b5: implications for protein-protein
      recognition.
AB  - Cytochrome b5 participates in electron-transfer reactions with a variety of
      different proteins. To explore how this protein might discern between
      structurally varied proteins, we have performed a molecular dynamics simulation
      focusing on its structural stability and dynamic behavior in solution. The
      protein was simulated in water at 298 K and pH 6.9 for 2.5 ns. The protein
      deviated significantly from the crystal structure midway through the simulation,
      but ultimately the crystalline conformation was regained. The simulation was at
      all times well behaved as judged by comparison to structural NMR data obtained in
      solution. One region of the protein backbone that deviated from the crystal
      conformation contains acidic residues implicated in electrostatic-based protein
      protein recognition. The mobility in this region caused the protein to display
      different patterns of residues at the surface with time, as well as the formation
      of a large cleft partially exposing the hydrophobic core lining the heme pocket.
      Furthermore, the position and cyclical formation of this cleft suggest that
      hydrophobic interactions may be important in protein-protein recognition events
      and possibly even electron transfer, as the cleft allows for easy access to the
      heme group. These results indicate that thermal motion could provide a low-energy
      mechanism for controlling recognition events. Thus, the dynamical behavior
      observed through the varying solution conformations sampled may be important in
      influencing the diverse range of protein-protein interactions in which cytochrome
      b5 participates.

PMID- 7626639
TI  - ATP-dependent inactivation of the beta-Ser339Cys mutant F1-ATPase from
      Escherichia coli by N-ethylmaleimide.
AB  - We introduced mutations at the highly-conserved residue Ser-339 in subunit beta
      of Escherichia coli F1-ATPase. The mutations beta S339Y and beta S339F abolished
      ATPase activity and impaired enzyme assembly. In contrast beta S339C F1 retained
      function to a substantial degree. N-Ethylmaleimide (NEM) at 0.2-0.3 mM
      inactivated beta S339C F1-ATPase by 80-95% in the presence of MgATP or MgADP but
      did not inactivate appreciably in absence of nucleotide or presence of EDTA. In
      absence of nucleotide, 0.7 mol of [14C-NEM] was incorporated into beta-subunits
      of 1.0 mol F1: in presence of MgATP the amount was 1.7 mol/mol, i.e. the
      introduced Cys residue became more accessible to reaction in the presence of
      MgATP. In the X-ray structure of F1 (Abrahams et al. (1994) Nature 370, 621-628)
      one of the catalytic nucleotide-binding domains is empty (on the "beta E
      subunit") and contains a cleft. Residue beta-339 lies within this cleft; the
      cleft does not occur in the other two beta-subunits. Our data are consistent with
      the conclusion that in wild-type enzyme under physiological conditions, MgATP or
      MgADP induce an enzyme conformation in which residue beta-Ser-339 becomes more
      exposed, possibly similar to the situation seen in the "beta E-subunit" in the X
      ray structure.

PMID- 7626640
TI  - Uracil DNA-glycosylase/glyceraldehyde-3-phosphate dehydrogenase is an Ap4A
      binding protein.
AB  - A 37 kDa protein that binds to diadenosine tetraphosphate (Ap4A) was purified
      from human HeLa cells and identified as uracil DNA glycosylase/glyceraldehyde-3
      phosphate dehydrogenase (UDG/GAPDH). Utilizing photoaffinity labeling with [alpha
      32P]8N3-Ap4A, an Ap4A binding protein of 37 kDa was identified from HeLa cell
      nuclear extracts. The 37 kDa protein was purified to homogeneity and subjected to
      trypsin digestion followed by amino acid sequence analysis. Two peptide sequences
      were determined and both had complete identity with the amino acid sequence of
      the 37 kDa polypeptide of UDG/GAPDH. Purified UDG/GAPDH binds to Ap4A with the
      same affinity as the HeLa cell nuclear 37 kDa Ap4A binding protein, and
      monoclonal antibodies to UDG/GAPDH cross-react with the 37 kDa Ap4A binding
      protein. UDG/GAPDH has been previously demonstrated to have numerous
      nonglycolytic activities. The UDG function is involved in DNA repair by excision
      of uracil from DNA. GAPDH is a RNA binding protein and binds to tRNA and AU-rich
      RNA. The AU-rich RNA binding has been implicated in the regulation of AU-rich
      element dependent mRNA turnover and translation. The identification of UDG/GAPDH
      as an Ap4A binding protein may be physiologically relevant to the proposed role
      of Ap4A as a regulatory nucleotide in cell growth.

PMID- 7626641
TI  - Differential scanning calorimetric study of the complexes of myosin subfragment 1
      with nucleoside diphosphates and vanadate or beryllium fluoride.
AB  - It has been recently shown by differential scanning calorimetry (DSC) that the
      formation of stable complexes of myosin subfragment 1 (S1) with Mg-ADP and
      orthovanadate (Vi) or beryllium fluoride (BeFx) causes a global conformational
      change in the S1 molecule which is reflected in a pronounced increase of S1
      thermal stability and in a significant change of S1 domain structure [Shriver, J.
      W., & Kamath U. (1990) Biochemistry 29, 2556-2564; Levitsky, D. I., Shnyrov, V.
      L., Khvorov, N. V., Bukatina, A. E., Vedenkina, N. S., Permyakov, E. A.,
      Nikolaeva, O. P., & Poglazov, B. F. (1992) Eur. J. Biochem. 209, 829-835; Bobkov,
      A. A., Khvorov, N. V., Golitsina, N. L., & Levitsky, D. I. (1993) FEBS Lett. 332,
      64-66]. In this work, which continues the previous investigations, we report on a
      DSC study of the complexes of S1 with various nucleoside diphosphates (NDP). In
      the absence of Vi or BeFx the various Mg(2+)-NDP and Mg(2+)-PPi had a similar
      effect on the S1 conformation. All of them had practically no influence on the
      temperature of the thermal transition but increased its sharpness. However, in
      the presence of Vi or BeFx the effects of Mg(2+)-NDP complexes were quite
      different from each other and strongly depended on the base structure of NDP;
      their effectiveness in inducing conformational changes in S1 and the stability of
      these complexes decreased in the following order: ADP > CDP >> UDP >> IDP >
      GDP.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7626642
TI  - The spongistatins, potently cytotoxic inhibitors of tubulin polymerization, bind
      in a distinct region of the vinca domain.
AB  - The highly cytotoxic, sponge-derived, antimitotic macrolide polyether
      spongistatin 1 has been previously shown to inhibit microtubule assembly, the
      binding of vinblastine and GTP to tubulin, and displacement of GDP bound in the
      exchangeable site of tubulin. We have now examined in detail inhibition by
      spongistatin 1 of both [3H]vinblastine and [3H]dolastatin 10 binding to tubulin.
      We found spongistatin 1 to be a noncompetitive inhibitor of the binding of both
      radiolabeled drugs to tubulin, in contrast to competitive patterns obtained with
      vincristine versus [3H]vinblastine and with a chiral isomer of dolastatin 10
      versus [3H]dolastatin 10. Since dolastatin 10 is itself a noncompetitive
      inhibitor of vinca alkaloid binding to tubulin, this implies at least three
      distinct binding sites for the structurally complex and diverse natural products
      that interfere with each others binding to tubulin and with nucleotide exchange.
      Spongistatin 1, in contrast to both vinca alkaloids and peptide antimitotic
      agents like dolastatin 10, does not induce formation of a GTP-independent,
      morphologically distinctive polymer ("aggregate"). We also examined eight
      compounds closely related structurally to spongistatin 1 (spongistatins 2-9). The
      most distinctive in their properties were spongistatins 6 and 8. These two
      compounds, despite activity comparable to spongistatin 1 as inhibitors of tubulin
      polymerization and [3H]vinblastine binding, had much reduced activity as
      inhibitors of nucleotide exchange and [3H]dolastatin 10 binding. Spongistatins 1
      and 6 were compared for effects on dolastatin 10-induced aggregate formation in
      conjunction with effects on [3H]dolastatin 10 binding. Spongistatin 6 was about 4
      fold less active than spongistatin 1 as an inhibitor of aggregation and over 20
      fold less active as an inhibitor of dolastatin 10 binding.

PMID- 7626643
TI  - Transmembrane signaling by the aspartate receptor: engineered disulfides reveal
      static regions of the subunit interface.
AB  - Ligand binding to the periplasmic domain of the transmembrane aspartate receptor
      generates an intramolecular conformational change which spans the bilayer and
      ultimately signals the cytoplasmic CheA histidine kinase, thereby triggering
      chemotaxis. The receptor is a homodimer stabilized by the interface between its
      two identical subunits: the present study investigates the role of the
      periplasmic and transmembrane regions of this interface in the mechanism of
      transmembrane signaling. Free cysteines and disulfide bonds are engineered into
      selected interfacial positions, and the resulting effects on the transmembrane
      signal are assayed by monitoring in vitro regulation of kinase activity. Three of
      the 14 engineered cysteine pairs examined, as well as six of the 14 engineered
      disulfides, cause perturbations of the interface structure which essentially
      destroy transmembrane regulation of the kinase. The remaining 11 cysteine pairs,
      and eight engineered disulfides covalently linking the two subunits at locations
      spanning positions 18-75, are observed to retain significant transmembrane kinase
      regulation. The eight functional disulfides positively identify adjacent faces of
      the two N-terminal helices in the native receptor dimer and indicate that large
      regions of the periplasmic and transmembrane subunit interface remain effectively
      static during the transmembrane signal. The results are consistent with a model
      in which the subunit interface plays a structural role, while the second membrane
      spanning helix transmits the ligand-induced signal across the bilayer to the
      kinase binding domain. The effects of engineered cysteines and disulfides on
      receptor methylation in vitro are also measured, enabling direct comparison of
      the in vitro methylation and phosphorylation assays.

PMID- 7626644
TI  - Glucose transporter function is controlled by transporter oligomeric structure. A
      single, intramolecular disulfide promotes GLUT1 tetramerization.
AB  - The human erythrocyte glucose transporter is an allosteric complex of four GLUT1
      proteins whose structure and substrate binding properties are stabilized by
      reductant-sensitive, noncovalent subunit interactions [Hebert, D. N., &
      Carruthers, A. (1992) J. Biol. Chem. 267, 23829-23838]. In the present study, we
      use biochemical and molecular approaches to isolate specific determinants of
      transporter oligomeric structure and transport function. When unfolded in
      denaturant, each subunit (GLUT1 protein) of the transporter complex exposes two
      sulfhydryl groups. Four additional thiol groups are accessible following subunit
      exposure to reductant. Assays of subunit disulfide bridge content suggest that
      two inaccessible sulfhydryl groups form an internal disulfide bridge.
      Differential alkylation/peptide mapping/N-terminal sequence analyses show that a
      GLUT1 carboxyl-terminal peptide (residues 232-492) contains three inaccessible
      sulfhydryl groups and that an N-terminal GLUT1 peptide (residues 147-261/299)
      contains two accessible thiols. The carboxyl-terminal peptide most likely
      contains the intramolecular disulfide bridge since neither its yield nor its
      electrophoretic mobility is altered by addition of reductant. Each GLUT1 cysteine
      was changed to serine by oligonucleotide-directed, in vitro mutagenesis. The
      resulting transport proteins were expressed in CHO cells and screened by
      immunofluorescence microscopy for their ability to expose tetrameric GLUT1
      specific epitopes. Serine substitution at cysteine residues 133, 201, 207, and
      429 does not inhibit exposure of tetrameric GLUT1-specific epitopes. Serine
      substitution at cysteines 347 or 421 prevents exposure of tetrameric GLUT1
      specific epitopes. Hydrodynamic analysis of GLUT1/GLUT4 chimeras expressed in and
      subsequently solubilized from CHO cells indicates that GLUT1 residues 1-199
      promote chimera dimerization and permit GLUT1/chimera heterotetramerization. This
      GLUT1 N-terminal domain is insufficient for chimera tetramerization which
      additionally requires GLUT1 residues 200-463. Extracellular reductants
      (dithiothreitol, beta-mercaptoethanol, or glutathione) reduce erythrocyte 3-O
      methylglucose uptake by up to 15-fold. This noncompetitive inhibition of sugar
      uptake is reversed by the cell-impermeant, oxidized glutathione. Reductant is
      without effect on sugar exit from erythrocytes. Dithiothreitol doubles the
      cytochalasin B binding capacity of erythrocyte-resident glucose transporter,
      abolishes allosteric interactions between substrate binding sites on adjacent
      subunits, and occludes tetrameric GLUT1-specific GLUT1 epitopes in situ. CHO cell
      resident GLUT1 structure and transport function are similarly affected by
      extracellular reductant. We conclude that each subunit of the glucose transporter
      contains an extracellular disulfide bridge (Cys347 and Cys421) that stabilizes
      transporter oligomeric structure and thereby accelerates transport function.

PMID- 7626645
TI  - Binding of monovalent cations to methylamine dehydrogenase in the semiquinone
      state and its effect on electron transfer.
AB  - The binding of monovalent cations to methylamine dehydrogenase in the semiquinone
      state (MADHsq) at a site close to the tryptophan tryptophylquinone (TTQ) active
      center is demonstrated in experiments which show that the radical EPR signal of
      MADHsq is considerably broadened in the presence of Cs+, NH4+, and, to a smaller
      extent, Na+. The cations also stabilize the semiquinone state, as is evident from
      the increase of the EPR intensity they induce. On the basis of the optical
      absorbance spectra, two slightly different forms of MADHsq can be discerned. One
      form, with the main band at 425 nm, is observed at low pH and in the presence of
      NH4+, whereas the other, with the main band at 429 nm, is observed at high pH and
      in the presence of Cs+ or Na+. Stopped-flow studies of the oxidation by amicyanin
      of MADHred via MADHsq to MADHox show a strong stimulation of the first step by
      monovalent cations. It is shown that it is primarily the actual electron transfer
      rate, rather than the affinity of MADHred for amicyanin, that is affected by
      cations. Values for the dissociation constants of the monovalent cations for
      MADHred, estimated from the kinetic experiments, are higher than those that were
      previously determined for MADHox, and can be deduced to be higher than those for
      MADHsq as well. The results are discussed within the context of the electron
      transfer theory.

PMID- 7626646
TI  - Bidirectional activity of the endoplasmic reticulum Ca(2+)-ATPase of bovine
      adrenal cortex.
AB  - It is generally accepted that the ryanodine receptor and the inositol 1,4,5
      trisphosphate receptor play major roles in the complex mechanisms by which
      agonists increase intracellular Ca2+ concentration. In these mechanisms, the
      endoplasmic reticulum Ca(2+)-ATPase has been attributed an accessory role of
      refilling the intracellular Ca2+ store. In the present study, the activity of the
      microsomal Ca(2+)-ATPase of bovine adrenal cortex was investigated. We show that
      the Ca(2+)-pumping activity of the Ca(2+)-ATPase is related to the ADP/ATP ratio.
      Our results also show that a brisk increase of the ADP/ATP ratio upon addition of
      exogenous ADP triggered a rapid release of Ca2+ from preloaded microsomes. ADP
      released Ca2+ in a dose-dependent manner with an EC50 of 2.98 +/- 0.78 mM. ADP
      induced Ca2+ release was not prevented by heparin, ruling out the participation
      of the inositol 1,4,5-trisphosphate receptor. ADP-induced Ca2+ release could not
      be attributed to the mere inhibition of the Ca(2+)-ATPase, since the rate of ADP
      induced Ca2+ release was 20 times faster than the rate of Ca2+ release induced by
      a maximal concentration of thapsigargin (2 microM). ADP-induced Ca2+ release
      experiments performed in the presence of [32P]PO4 revealed a concomitant
      production of [32P]ATP. ADP-induced [32P]ATP production was dose-dependent, with
      an EC50 of 5.50 +/- 0.70 mM. ADP-induced [32P]ATP production was prevented by
      ionomycin (10 microM) and by high concentrations of extramicrosomal Ca2+. These
      results demonstrate that the microsomal Ca(2+)-ATPase of adrenal cortex possesses
      a bidirectional activity that depends on ADP concentrations, the Ca2+ gradient
      across the microsomal membrane, and probably also ATP concentrations.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7626647
TI  - Rapid substrate translocation by the multisubunit, erythroid glucose transporter
      requires subunit associations but not cooperative ligand binding.
AB  - The human erythroid glucose transporter is a GLUT1 homotetramer whose structure
      and function are stabilized by noncovalent, cooperative subunit interactions. The
      present study demonstrates that exofacial tryptic digestion of GLUT1 abolishes
      cooperative interactions between substrate binding sites on adjacent subunits
      under circumstances where subunit associations and high catalytic turnover are
      maintained. Extracellular trypsin produces rapid, quantitative cleavage of the
      human red cell-resident sugar transport protein, GLUT1. One major carboxyl
      terminal peptide of M(r)(app) 25,000 is detected by immunoblot analysis.
      Endofacial tryptic digestion of GLUT1 results in the complete loss of GLUT1
      carboxyl-terminal structure. GLUT1-mediated erythrocyte sugar uptake, transport
      inhibition by cytochalasin B, and GLUT1 oligomeric structure are unaffected by
      exofacial GLUT1 proteolysis. In contrast, the cytochalasin B binding capacity of
      GLUT1 and the Kd(app) for cytochalasin B binding to the transporter are doubled
      following exofacial tryptic digestion of GLUT1. Photoaffinity labeling
      experiments show that increased cytochalasin B binding results from increased
      ligand binding to the 25 kDa carboxyl-terminal GLUT1 peptide. Proteolysis
      abolishes allosteric interactions between sugar import (maltose binding) and
      sugar export (cytochalasin B binding) sites that normally exist on adjacent
      subunits within the transporter complex, but interact with negative
      cooperativity. Following exofacial proteolysis, these sites become mutually
      exclusive. Dithiothreitol disrupts GLUT1 quaternary structure, inhibits 3-O
      methylglucose transport, and abolishes cooperative interactions between sugar
      import and export sites in control cells. Studies with reconstituted purified
      GLUT1 confirm that the action of trypsin on cytochalasin B binding is direct,
      show that proteolysis increases the apparent affinity of the sugar efflux site
      for transported sugars, and suggest that the membrane bilayer stabilizes GLUT1
      noncovalent structure and catalytic function following GLUT1 proteolysis.
      Collectively, these findings demonstrate that GLUT1 does not require an intact
      polypeptide backbone for catalytic function. They show that the multisite sugar
      transporter mechanism is converted to a simple ping-pong carrier mechanism
      following exofacial GLUT1 proteolysis. They reveal that subunit cooperativity can
      be lost under circumstances where cohesive structural interactions between
      transporter subunits are maintained. They also refute the hypothesis [Hebert, D.
      N., & Carruthers, A. (1992) J. Biol. Chem. 267, 23829-23838] that rapid substrate
      translocation by the multisubunit erythroid glucose transporter requires
      cooperative interactions between subunit ligand binding sites.

PMID- 7626648
TI  - A short autocomplementary sequence in the 5' leader region is responsible for
      dimerization of MoMuLV genomic RNA.
AB  - Previous work has shown that a region of Moloney murine leukemia virus (MoMuLV)
      RNA located between nucleotides 280 and 330 in the PSI region (nt 215-565) is
      implicated in the dimerization process. We show with a deletion from nucleotides
      290-299 in PSI RNA transcripts and through an antisense oligonucleotide
      complementary to nucleotides 275-291 that the 283-298 region is involved in RNA
      dimer formation in vitro. In an attempt to further characterize the mechanism of
      dimer formation, a series of short RNA transcripts was synthesized which
      overlapps the PSI region of MoMuLV RNA. The dimerization of these RNAs is
      temperature dependent. The predicted secondary structure of the 278-303 region,
      as a function of temperature, reveals that this sequence is able to adopt two
      conformations: (1) the U288 AGCUA293 sequence in a loop; (2) part of the same
      nucleotides implicated in a stem. These results, together with thermodynamic
      analysis, strongly suggest that (1) the loop conformation of the UAGCUA sequence
      modulates the relative amount of RNA dimer and (2) a 16 bp long Watson-Crick base
      pairing is involved in RNA dimer formation. We propose that loop-loop recognition
      via the U288 AGCUA293 sequence leads to a stable structure induced by a stem-loop
      opening. Furthermore, our results do not support purine quartet formation as
      necessary for the dimerization of the 5' leader MoMuLV RNA.

PMID- 7626649
TI  - Nucleotide binding to the 43-kilodalton N-terminal fragment of the DNA gyrase B
      protein.
AB  - The binding of ADPNP (5'-adenylyl beta,gamma-imidodiphosphate) to the 43-kDa N
      terminal fragment of the DNA gyrase B protein is found to stabilize a dimer of
      the protein. Analysis of the kinetics of binding of ADPNP to the fragment
      suggests that protein dimers can contain 1 or 2 molecules of bound nucleotide.
      ATP, ADP, or coumarin drugs inhibit the binding of ADPNP. The rate of
      dissociation of ADPNP from the 43-kDa protein is found to be very slow and
      unaffected by the presence of other nucleotides. These data can be accommodated
      by a scheme in which the 43-kDa monomer forms a short-lived complex with ADPNP
      that can be converted into long-lived dimer complexes containing either 1 or 2
      molecules of bound ADPNP; dimer formation with 2 bound ADPNPs is strongly
      favored. Coumarin drugs inhibit the binding of ADPNP to the 43-kDa fragment, with
      novobiocin binding to the protein with a stoichiometry of 1:1 and coumermycin
      binding with a stoichiometry of 0.5:1.

PMID- 7626650
TI  - RuvB protein-mediated ATP hydrolysis: functional asymmetry in the RuvB hexamer.
AB  - A survey of RuvB protein-mediated ATP hydrolysis yields the following
      observations. (1) The RuvB protein exhibits a DNA-independent ATPase activity
      with a turnover number (based on a RuvB monomer) approaching 6 min-1 and a Km of
      154 microM. Single-stranded DNA and linear duplex DNA have small but significant
      effects on this activity. (2) At ATP concentrations near the Km, the ATPase
      activity is attenuated after approximately 60 turnovers/RuvB monomer. The
      attenuation does not reflect inhibition by ADP. Addition of ATP to 3 mM triggers
      an immediate resumption of ATP hydrolysis. The attention is enhanced somewhat by
      ssDNA and reduced somewhat by linear dsDNA. (3) ATP hydrolysis is dramatically
      stimulated by circular dsDNA, reinforcing the notion that RuvB translocates along
      the DNA in a reaction coupled to ATP hydrolysis. The kcat increases by at least 2
      4-fold on circular duplexes depending on conditions, and the inactivation of RuvB
      at ATP concentrations near the Km does not occur. The ATPase activity on circular
      dsDNA also exhibits a partial substrate inhibition by ATP. (4) Optimal ATP
      hydrolysis requires approximately 1 DNA circle/RuvB hexamer, suggesting that
      multiple RuvB hexamers on a circle have an inhibitory effect on the ATPase
      activity. (5) With or without any of these DNA cofactors, a burst of ATP
      hydrolysis is observed under pre-steady-state conditions equivalent to 1 ATP per
      3-3.3 RuvB monomers (2 ATP/hexamer). The substrate inhibition and burst results
      suggest the presence of nonequivalent ATP hydrolytic sites in a RuvB hexamer. The
      attenuation of ATPase activity observed under some conditions may also be a
      manifestation of nonequivalent ATP hydrolytic sites.

PMID- 7626651
TI  - Serum response factor: transcriptional regulation of genes induced by growth
      factors and differentiation.

PMID- 7626652
TI  - c-Myc and apoptosis.

PMID- 7626653
TI  - Genetic analysis of cellular senescence.

PMID- 7626654
TI  - Neurofibromatosis type 1 and Ras-mediated signaling: filling in the GAPs.

PMID- 7626655
TI  - Prazosin reduces myocardial ischemia/reperfusion-induced Ca2+ overloading in rat
      heart by inhibiting phosphoinositide signaling.
AB  - The aim of this study was to establish whether or not alpha 1-adrenergic
      receptors are implicated in triggering phosphoinositide hydrolysis and
      intracellular Ca2+ accumulation during myocardial ischemia and reperfusion. In
      isolated perfused rat hearts, the selective alpha 1-receptor antagonist prazosin
      abolished the increase in radioactivity incorporation into cellular inositol
      phosphates induced by 30 min ischemia followed by 30 min reperfusion, and
      selectively blocked the degradation of phosphoinositides; only minor changes in
      the ischemia/reperfusion-induced loss of other classes of phospholipids were
      seen. In addition, a prazosin-induced decrease of ischemia/reperfusion Ca2+
      overloading was documented in real-time recordings of epicardial cytosolic free
      Ca2+ in fura 2-loaded hearts. An inhibition of early ischemic Ca2+ rise was
      observed, as well as a lower peak of cytosolic free Ca2+ and a more rapid
      reversal to normal values during reperfusion. Moreover, alpha 1-adrenergic
      blockade resulted in a significant improvement in the recovery of myocardial
      function during reperfusion: an increased left ventricular developed pressure and
      maximum rate of rise of systolic pressure paralleled the decrease in time
      averaged cytosolic Ca2+ and the increase in amplitude of Ca2+ transients,
      respectively. It is concluded that myocardial Ca2+ overloading during ischemia
      and reperfusion may be triggered by alpha 1-adrenergic receptor-induced
      polyphosphoinositide hydrolysis.

PMID- 7626656
TI  - Rat fibroblasts synthesize T-kininogen in response to cyclic-AMP, prostaglandin
      E2 and cytokines.
AB  - T-Kininogen is a plasma protein characterized as a kinin-precursor, a cysteine
      protease inhibitor and an acute phase protein in the rat. Rat fibroblasts
      prepared from meninges or embryos and 3Y1-B clone 1-6 cells, a rat fibroblast
      cell line, secreted T-kininogen. Incubating these cells with 1 mM Bt2cAMP or a
      combination with 1 microM dexamethasone resulted in a marked increase in T
      kininogen secretion, as well as in the incorporation of radioactive methionine
      into newly synthesized T-kininogen. Secretion of T-kininogen by meningeal
      fibroblasts was stimulated by forskolin, prostaglandin E2, bradykinin and
      cytokines, such as tumor necrosis factor alpha, interleukin-1 alpha (IL-1) and IL
      6. Expression of T-kininogen mRNA was demonstrated in meningeal fibroblasts by
      Northern blot hybridization using T-kininogen cDNA as a probe, and the expression
      was stimulated by Bt2cAMP, prostaglandin E2, and the cytokines described above.
      In contrast, expression of T-kininogen mRNA in rat hepatocytes was not altered by
      Bt2cAMP, prostaglandin E2, tumor necrosis factor and IL-1, whereas it was greatly
      stimulated by IL-6, suggesting the differential regulation of T-kininogen gene
      expression in fibroblasts and hepatocytes. These results demonstrated for the
      first time, that rat fibroblasts express the T-kininogen gene, and that the
      expression is regulated by inflammatory mediators and cytokines.

PMID- 7626657
TI  - Ethanol-induced modification of somatostatin-responsive adenylyl cyclase in rat
      exocrine pancreas.
AB  - Male rats were given 10% (w/v) ethanol in drinking fluid during the first week,
      15% (w/v) during the second week, 20% (w/v) during the third, and 25% (w/v)
      during the fourth week, at the end of which they were kept on 25% (w/v) ethanol
      drinking water for 3 weeks. Some animals were then allowed the withdrawal of
      ethanol for a period of 2 weeks or 7 weeks. No significant differences were seen
      for the basal and forskolin (FK)-stimulated adenylate cyclase (AC) enzyme
      activities in the pancreatic acinar membranes of ethanol-treated and ethanol
      withdrawal rats as compared to the control group. Chronic ethanol ingestion
      resulted in an attenuation of somatostatin(SS)-inhibited FK-stimulated AC in rat
      pancreatic acinar membranes. The ability of the stable GTP analogue 5'
      guanylylimidodiphosphate (Gpp[NH]p) to inhibit FK-stimulated AC activity was also
      decreased in pancreatic acinar membranes from ethanol-treated rats. Gpp[NH]p was
      a much less potent inhibitor of SS binding in the pancreatic acinar membranes
      from chronic ethanol-treated animals than in those from controls, suggesting a
      change of Gi. A significant reduction in the number of 125I-Tyr11-SS receptors
      was observed after ethanol ingestion, when compared with control values. Two
      weeks after the replacement of the ethanol solution by water, the ethanol effect
      on the parameters cited above persisted. At week 7 of withdrawal, these
      parameters reached the level of water controls. Ethanol administration did not
      affect either the number or the affinity of secretin receptors as compared to
      control values which suggests that the change in SS binding is not a non-specific
      effect. Neither chronic ethanol consumption nor withdrawal affected somatostatin
      like immunoreactivity (SSLI). These results suggest that the attenuated
      inhibition of AC by SS in pancreatic acinar membranes from ethanol-treated rats
      and ethanol withdrawal (2 weeks) rats may be caused by decreases in both Gi
      activity and in the number of SS receptors. Alternatively, an uncoupling of SS
      receptors from Gi and/or a decrease in the level of functional Gi may result in
      both a decrease in apparent Bmax for SS binding and in SS-mediated inhibition of
      AC. Since SS has been suggested to be an inhibitor of basal and cholecystokinin
      (CCK)- and/or secretin-stimulated exocrine pancreatic secretion, it is tempting
      to speculate that the impairment of the SS receptor/effector system seen in the
      present study can participate in the increase of basal pancreatic exocrine
      secretion described after chronic ethanol consumption.

PMID- 7626658
TI  - Quantitative analysis of redox gradient within the rat liver acini by
      fluorescence images: effects of glucagon perfusion.
AB  - The redox gradient along the sinusoid in the rat liver was studied using a redox
      scanner, a device based on tissue fluorescence scanning spectroscopy measuring
      the fluorescence signals of oxidized flavoprotein (FP) and reduced pyridine
      nucleotide (PN). The FP/(FP+PN) ratio reflects the mitochondrial redox state in
      the liver tissue. The distribution of mitochondrial redox state on the scanned
      area is expressed as two-dimensional gray-scale images with a 20 micron
      resolution. Using this instrument, we have scanned a 2.5 x 2.5 mm area of the
      frozen rat liver sample to investigate the redox gradient within acini and the
      effects of glucagon on the changes in the redox distribution. The redox images
      obtained in the perfused livers showed mosaic patterns implicating a regular
      heterogeneity of redox state in an acinus. The analysis of gradient curve,
      furthermore, clarified that the redox level in an acinus decreased sigmoidally
      from the periportal to the pericentral region. Glucagon, which has been reported
      to reduce the intracellular redox state, decreased the redox potential in whole
      acini, especially, in the periportal region, when compared with the perfusion
      without glucagon. These results strongly indicate an intraacinus heterogeneity of
      glucagon function, with glucagon selectively operating in the upstream of the
      sinusoid.

PMID- 7626659
TI  - Intracellular degradation of type I collagen and fibronectin in human lung
      fibroblasts: evidence against degradation in pre-lysosomal compartments.
AB  - Fibroblasts degrade about 15% of newly synthesised collagen within the cell
      before it can be secreted. When the helical structure of collagen is disrupted,
      about 30% is degraded intracellularly. To determine if collagen degradation
      occurs in a pre-lysosomal compartment, the passage of type 1 collagen out of the
      endoplasmic reticulum or Golgi was inhibited by incubating human lung fibroblasts
      with brefeldin A or monensin. In both cases, the type I collagen retained within
      the cell was stable over a 20 h period. Disrupting the helical structure of
      collagen with cis-hydroxyproline, 2,2'-bipyridyl or ethyl 3,4-dihydroxybenzoate
      did not alter the stability of type I collagen in brefeldin or monensin-treated
      cells. Incubating permeabilised cells in the presence of GTP gamma S (guanosine
      5'-(3-O-thio)triphosphate), which blocks transport out of the endoplasmic
      reticulum, also resulted in the stable retention of type I collagen. Addition of
      dithiothreitol to permeabilised cells failed to initiate intracellular
      degradation. Similar results were obtained with fibronectin. Both normal
      fibronectin and fibronectin in which canavanine replaced arginine were stable for
      20 h in cells treated with brefeldin A or monensin. The degradation of native
      collagen is sensitive to inhibition by a cell-permeable cysteine proteinase
      inhibitor (ALLN) but is insensitive to chloroquine (which raises the pH of acidic
      intracellular compartments), whereas the degradation of abnormal collagen was
      sensitive to both ALLN and chloroquine. These results argue against the
      intracellular degradation of collagen or fibronectin in a pre-lysosomal
      compartment.

PMID- 7626660
TI  - Alterations in superoxide dismutase and catalase in Fusarium oxysporum during
      starvation-induced differentiation.
AB  - Vegetative hyphae of Fusarium oxysporum differentiate into chlamydospore by
      triggering with carbon-starvation. The current changes in the cellular
      detoxifying defenses against superoxide and hydrogen peroxide: superoxide
      dismutase (SOD) and catalase, were examined. Although there was a little change
      in catalase, a dramatic change in SOD was observed during the differentiation. In
      vegetative hyphae of F. oxysporum f. sp. raphani, three isozymes of SOD, all of
      which were not inhibited by hydrogen peroxide and cyanide, were present whereas
      in chlamydospore an isoenzyme, which was inhibited by hydrogen peroxide but not
      by cyanide, was present. Thus, as differentiation proceeded, Mn-type SOD
      disappeared and an Fe-type SOD appeared. The results suggest that the Fe-type SOD
      is specifically expressed during chlamydospore formation and that active
      intermediates of oxygen and/or its scavenging enzymes participate in the
      differentiation of Fusarium oxysporum.

PMID- 7626661
TI  - Intracellular pH of Candida albicans blastospores as measured by laser
      microspectrofluorimetry and 31P-NMR.
AB  - The intracellular pH (pHi) of Candida albicans blastospores harvested from 8 h or
      48 h cultures was determined under identical experimental conditions by two
      different techniques: 31P-NMR and laser microspectrofluorimetry. Time dependence
      of pHi was monitored by 31P-NMR on the whole cell population.
      Microspectrofluorimetry, after loading of the cells with SNARF-1, enabled the
      determination of pHi in isolated cells and its distribution among the cell
      population. By this method, the vacuolar pH could not be distinguished from the
      cytoplasmic pH in C. albicans blastospores, but alkalization of pHi was observed
      at the beginning of germ tubes. The absolute values of pHi determined by 31P-NMR
      were slightly different from those obtained by laser microspectrofluorimetry.
      However, the pH distributions in the cell population were converging. For
      blastospores in exponential phase a gaussian distribution of pHi was observed
      with both methods, the cells maintained a steady pHi value when the external pH
      was varied from 5.5 to 8.5. For cells in stationary phase two pools were
      identified: the combination of the two techniques demonstrated the presence of
      two different subpopulations. One of these population (with lower pH) was able to
      commute to the other one with time as shown by 31P-NMR kinetics. This information
      is reported here for the first time in C. albicans.

PMID- 7626662
TI  - Modifications of pH and K+ gradients in Candida albicans blastospores induced by
      amphotericin B. A 31P NMR and K+ atomic absorption study.
AB  - Candida albicans blastospores harvested from 8 h (exponential) or 48 h
      (stationary) cultures were incubated with increasing doses of amphotericin B
      (AmB). The time course of H+ influx and K+ efflux was monitored by in vivo 31P
      NMR and K+ atomic absorption respectively. AmB was shown to be more active on
      exponential phase cells than on stationary phase cells. For both growth phases,
      K+ leakage occurred before pH acidification. In light of these results, together
      with iodoacetate experiments, it seems difficult to assert that K+ leakage is a
      secondary effect resulting from an increase in the permeability to protons, as
      formerly proposed. In addition, no H+ over K+ selectivity of pores formed by AmB
      could be detected. Finally, some unexpected results were afforded by 31P NMR
      experiments: a broadening of Pi signals was detected on exponential phase cell
      spectra when the blastospores were incubated with 10(-3) and 10(-4) M AmB
      reflecting a transient heterogeneity of the intracellular pH within the cell
      population. For stationary phase blastospores, two subpopulations (IIa and IIb)
      were detected; population IIb, with a more acidic pHi, was much more sensitive to
      AmB action.

PMID- 7626663
TI  - Consequences of the overexpression of ubiquitin in yeast: elevated tolerances of
      osmostress, ethanol and canavanine, yet reduced tolerances of cadmium, arsenite
      and paromomycin.
AB  - Ubiquitin is induced by diverse stresses in all eukaroytes probably in reflection
      of the need for more extensive protein turnover by the ubiquitination system in
      stressed cells. To determine if ubiquitin overexpression can confer general
      protection against different stresses, yeast cells were engineered to overexpress
      ubiquitin and the effects of this overexpression on different stress tolerances
      determined. Ethanol and osmostress tolerances were slightly increased by
      ubiquitin overexpression, tolerance to heat was unaffected, while still other
      tolerances were reduced as compared to cells with normal ubiquitin levels. It is
      noteworthy that tolerance of the amino acid analogue canavanine was markedly
      increased by ubiquitin overexpression, yet resistance to at least three other
      agents that contribute to accumulation of aberrant proteins (arsenite, cadmium,
      paromomycin) was decreased.

PMID- 7626665
TI  - Extracellular ATP inhibits agonist-induced mobilization of internal calcium in
      human platelets.
AB  - Our previous studies have demonstrated that platelets possess ATP purinergic
      receptors in addition to the ADP, P2T, receptor. Occupancy of the P2 receptor by
      ATP inhibited agonist-induced platelet aggregation. This study demonstrated that
      the mechanism of inhibition may involve ATP inhibition of agonist-induced
      mobilization of internal calcium. Within the cardiovascular system, the ATP
      inhibition of calcium mobilization is unique to platelets. All other cell types
      in the cardiovascular system, where calcium mobilization is affected by
      extracellular ATP, responded with an increased mobilization as opposed to
      inhibition. The platelet inhibitory response to ATP was enhanced by the addition
      of an ATP generating system, creatine phosphate/phosphocreatine kinase. ATP and
      ATP analogues were found to inhibit calcium mobilization with a rank order of
      alpha beta-methylene ATP, beta gamma-methylene ATP approximately ATP > benzoyl
      ATP > 2 methylthio ATP which is a characteristic of P2x-like receptors. The
      inhibitory effect of ATP could be abrogated by prolonged treatment of platelets
      with the P2x desensitizing agent, alpha beta-methylene ATP. Also, UTP and CTP
      were approximately as effective inhibitors as ATP while GTP was not. ATP
      competition with ADP for the P2T receptor was excluded in studies with platelets
      derived from an aspirin-treated individual which were essentially insensitive to
      ADP. The agonist-induced calcium mobilization and inhibition by ATP occurred with
      the thromboxane A2 mimetic, U46619, collagen and thrombin; however, the kinetics
      of mobilization varied somewhat with the different agonists. The responses to
      extracellular ATP were independent of extracellular Ca2+, where 1 mM calcium or
      0.3 mM EGTA was added to the reaction mixture. The inhibition of calcium
      mobilization coupled to inhibition of platelet aggregation by extracellular ATP
      may serve an important physiologic role. ATP, released from activated platelets
      at localized sites of vascular injury, may help to limit the size of the platelet
      plug-clot that, if left unregulated, could occlude the injured blood vessel.

PMID- 7626664
TI  - Stimulation of urokinase expression by TNF-alpha requires the activation of
      binding sites for the AP-1 and PEA3 transcription factors.
AB  - The urokinase-type plasminogen activator plays a central role in tissue
      remodeling by controlling the synthesis of the extracellular matrix-degrading
      plasmin. Urokinase expression is transcriptionally regulated by a variety of
      cytokines including TNF-alpha. The present study was undertaken to identify key
      transcription factor binding sites in the urokinase promoter necessary for the
      TNF-alpha-dependent induction of urokinase expression. TNF-alpha treatment of a
      squamous cell carcinoma cell line, UM-SCC-1, which produces no detectable TNF
      alpha, led to a dose-dependent increase in urokinase secretion, thus reflecting a
      more abundant mRNA. Transient transfections of UM-SCC-1 cells with a CAT reporter
      driven by 5' deletion fragments of the urokinase promoter indicated that a
      sequence spanning -2109 to -1870, which contained binding sites for AP-1 and PEA3
      was required for the stimulation by TNF-alpha. Mutation of an AP-1 binding site
      at -1967 and a PEA3 motif at -1973 completely abrogated the inductive effect of
      TNF-alpha on urokinase promoter activity. Mobility shift assays indicated the
      presence of a jun-containing factor(s) which bound specifically to the AP-1
      sequence present in the urokinase promoter. The amount and/or activity of this
      factor(s) was greatly enhanced by TNF-alpha treatment. UM-SCC-1 cells transiently
      transfected with a CAT reporter driven by 3 tandem AP-1 binding sites
      demonstrated increased CAT activity following TNF-alpha treatment. Thus, the
      induction of urokinase expression by TNF-alpha is likely to involve the altered
      expression and/or activity of transcription factors which bind to the AP-1 and
      PEA3 target sequences in the urokinase promoter.

PMID- 7626666
TI  - Rotational asymmetry of Escherichia coli flagellar motor in the presence of
      arsenate.
AB  - The flagellar motor of Escherichia coli (E. coli) is driven by a proton-motive
      force (PMF), hence it was of interest to determine whether the motor is
      symmetrical in the sense that it can be rotated by any polarity of PMF. For this
      purpose the cells had to be deenergized first. Conventional deenergization
      procedures caused irreversible loss of motility, presumably due to ATP-dependent
      degradative processes. However, E. coli cells deenergized by incubation with
      arsenate manifested a slow, reversible depletion of PMF. In this procedure there
      was a sufficiently long time window, during which a considerable proportion of
      the cells lost their motility and could be made to rotate again by an
      artificially-imposed PMF. The motors of these cells rotated in response to any
      PMF polarity, but positive and negative polarities rotated different sub
      populations of cells and the direction was almost exclusively counterclockwise.
      The reason for the unidirectionality of the rotation was not the intervention of
      the chemotaxis system. A number of potential reasons are suggested. One is the
      arsenate effect on the motor function found previously [Margolin, Y., Barak, R.
      and Eisenbach, M. (1994) J. Bacteriol. 176, 5547-5549]. A possible interaction
      between arsenate and the motor is discussed.

PMID- 7626667
TI  - Acute stimulation of glucose transport by histamine in cardiac microvascular
      endothelial cells.
AB  - The purpose of the present work was to study the acute regulation of glucose
      uptake in cultured cardiac endothelial cells (CEC). Two types of potential
      stimuli were considered: (1) agents that are known to acutely stimulate glucose
      transport (i.e., within minutes) in fat and muscle tissues and (2) agents that
      influence endothelial cell function. Among the former agents, neither insulin,
      nor catecholamines (adrenaline, dopamine, phenylephrine), nor serotonin affected
      the rate of glucose transport in CEC, while SH-group reagents (phenylarsine
      oxide, diamide or menadione) were inhibitory. Among the factors of the second
      group that were tested (heparin, ADP, histamine, bradykinin), histamine was found
      to stimulate glucose transport in CEC by 10-50%. This effect was concentration
      dependent (with an EC50 value approximately equal to 12 microM) and reached a
      maximum within 5 min upon histamine addition. This stimulation of glucose
      transport was suppressed by pyrilamine (100 nM), a specific H1-receptor
      antagonist, but not by cimetidine (100 microM), a H2-selective antagonist.
      Northern blot and Western blot analysis of CEC extracts revealed the presence of
      the ubiquitous glucose transporter isoform GLUT1 mRNA and protein, but not of the
      'insulin-regulatable' isoform GLUT4. In conclusion, this is the first report on
      an acute stimulation of glucose transport in cardiac endothelial cells, in
      particular, and in an insulin-unresponsive cell type, in general. The effect of
      histamine is most likely mediated by H1-receptors and cannot be accounted for by
      a recruitment of GLUT4.

PMID- 7626668
TI  - Recognition of sialosaccharide chains of glycophorin on damaged erythrocytes by
      macrophage scavenger receptors.
AB  - Binding of mouse erythrocytes oxidized in vitro mildly with diamide, periodate or
      ADP/Fe3+, and the erythrocytes incubated in vitro in a serum-free medium for 12 h
      (in vitro aged erythrocytes) to mouse peritoneal macrophages was effectively
      inhibited by isolated glycophorin A, a major sialoglycoprotein of human
      erythrocyte membrane existing as oligomers in solution, and some of known ligands
      for macrophage scavenger receptors such as maleyl-BSA, dextran sulfate, fucoidan
      and polyinosinic acid. Binding of oxidized low density lipoprotein (ox-LDL) to
      macrophages was inhibited by glycophorin A as well as the known ligands. When the
      sialyl residues of the saccharide chains of glycophorin A were cleaved by
      neuraminidase, or the polypeptide of glycophorin A was digested by Pronase, which
      would destroy its oligomeric forms, the inhibitory effect of glycophorin A was
      decreased, suggesting that isolated glycophorin A binds to scavenger receptors
      depending on its sialyl residues and oligomeric structure. Glycopeptides prepared
      from the N-terminal region of glycophorin A containing most of the
      sialosaccharide chains of the molecule inhibited the binding of ox-LDL although
      the potency was lower than that of glycophorin A. N-Acetylneuraminic acid at a
      high concentration also inhibited the ox-LDL binding. Uptake and degradation of
      125I-labeled ox-LDL by macrophages was inhibited by glycophorin A, N
      acetylneuramin lactose, as well as the known ligands. 125I-labeled glycophorin A
      bound to macrophages, and the binding was inhibited by the unlabeled glycophorin
      A and the known ligands. Inhibitory activity of the unlabeled glycophorin A
      against the labeled glycophorin A-binding was lowered by neuraminidase and
      Pronase treatment. These results suggest that oxidized and in vitro aged mouse
      erythrocytes are recognized by scavenger receptors of mouse peritoneal
      macrophages, and the cell surface components recognized are sialosaccharide
      chains of glycophorin, possibly glycophorin A counterpart of mouse erythrocytes
      which clustered or aggregated in the membrane. The finding indicates that the
      cell surface sialosaccharides can be ligands for scavenger receptors when cells
      undergo denaturation by oxidative stress or other damaging effects.

PMID- 7626669
TI  - What does the community need from its public health workers?

PMID- 7626670
TI  - The 1995 federal budget and a national health promotion policy.

PMID- 7626671
TI  - An open letter to the president of the Public Health Association.

PMID- 7626672
TI  - From Papua New Guinea to the United Nations: the prevention of mental defect due
      to iodine deficiency.

PMID- 7626673
TI  - The public health significance of cannabis use in Australia.
AB  - A fair appraisal of the public health significance of cannabis use has been
      hampered by the polarised opinions about its health effects expressed by
      partisans on both sides of the debate on its legal status. The findings of a
      recent review of the literature on the adverse health and psychological effects
      of cannabis are used to estimate the major probable public health risks of
      cannabis use in Australia. These appear to be, in order of approximate public
      health importance: adverse psychological effects; motor vehicle accidents;
      cannabis dependence; respiratory disease; precipitation and exacerbation of
      schizophrenia in vulnerable individuals; low-birthweight babies; and perhaps
      subtle cognitive impairment. On current patterns of use, cannabis use is a modest
      public health concern by comparison with alcohol and tobacco, although given the
      scale of public health damage caused by the latter drugs, and the currently low
      prevalence of regular cannabis use, this is not cause for complacency.

PMID- 7626674
TI  - Public health and the Australian Constitution.
AB  - The powers vested in the Commonwealth Government by the Constitution contain the
      basis of much public health law in Australia. Yet this is not often recognised;
      public health law is generally, and historically, seen as the states'
      responsibility. This article surveys the broad range of constitutional powers
      that the Commonwealth Government can rely upon to make public health laws. It
      considers areas of power specified in the Constitution, such as those with
      respect to external affairs and corporations. Decisions of the High Court have
      interpreted the various heads of power very broadly and have significantly
      enhanced the potential of the Commonwealth to pass detailed and far-reaching
      public health law. To this fact must be added the taxation arrangements in
      Australia and, with these, the very extensive control that the Commonwealth can
      exercise through its monopoly of major taxation sources. Its power to make
      financial arrangements can tie dependent states into specific policies (including
      public health policies) as a condition of the grants made to them. However, these
      broad powers may be limited in some important respects: the High Court is
      increasingly identifying rights and freedoms in the Constitution that may
      increasingly bring both state and Commonwealth public health law under challenge.
      Despite this possibility, the Commonwealth may prove to be our most significant
      source of public health law, and public health policy makers should recognise the
      full potential of its power to make such laws.

PMID- 7626675
TI  - Record linkage in Australian epidemiological research: health benefits, privacy
      safeguards and future potential.
AB  - Epidemiologists are increasingly concerned with the health effects of
      interventions and of exposure to noninfectious agents, but there may be long
      periods between exposure and outcome. Collecting information from respondents is
      a costly and often inefficient way of obtaining the longitudinal data necessary
      to study these effects. Linking existing data can be an effective and efficient
      alternative. However, it is often not practicable to obtain informed consent from
      the individuals whose records are to be linked. This raises important issues
      relating to protection of privacy. This paper examines the health benefits and
      privacy issues of epidemiological and health services research involving record
      linkage in Australia. The future potential for studies based on record linkage is
      discussed in the context of recent national and international developments in
      data protection. In the interests of public health and the rational use of health
      resources a balance must be struck between protecting individual privacy and
      conducting such health research for the common good.

PMID- 7626676
TI  - Problems of focus group methods in cross-cultural research: a case study of
      beliefs about sudden infant death syndrome.
AB  - Over the past decade there has been increasing interest in using focus group
      methods in public health research. Focus group discussions have become
      particularly popular, in part because they are commonly perceived to be a less
      time-consuming and less expensive way of collecting qualitative data than the
      more traditional ethnographic methods. However, little attention has been given
      to methodological issues when the focus group method is applied in cross-cultural
      settings. This paper discusses a number of these concerns, illustrated through
      the use of the focus groups to explore mothers' beliefs about sudden infant death
      syndrome (SIDS) in an ethnically diverse sample in Victoria. We found that some
      methodological difficulties were related to cultural factors. This has led us to
      use caution when considering the use of focused group discussions as a research
      method in cross-cultural contexts. We urge public health researchers to take a
      critical look at the appropriateness of focus groups before applying this method
      in cross-cultural public health research.

PMID- 7626677
TI  - Setting targets: a three-stage model for determining priorities for health
      promotion.
AB  - This paper describes a three-stage model for setting targets for health
      promotion. The model was developed in 1992 in response to the need to identify
      priority areas for health promotion for women in the Hunter Region of New South
      Wales. The approach enabled epidemiological data and views from the community to
      be synthesised and integrated with those of experts from health and social
      services (key informants), using a nominal group process. The reliability of the
      method was investigated by replicating the process with two groups of key
      informants. There was considerable commonality in the targets generated by the
      two groups. The process resulted in the identification of seven targets that
      reflected the concerns of the community and local experts as well as the health
      priorities suggested by local epidemiological data. The model used could be
      adapted for determining priorities in a wide range of health and health care
      settings, where available resources restrict the range of services or activities
      which can be offered.

PMID- 7626678
TI  - Prevalence of dementia among patients referred to an aged care assessment team
      and associated stress in their carers.
AB  - The objective of this study was to determine the prevalence of dementia among
      patients referred to an aged care assessment team and to compare levels of burden
      and psychological morbidity between carers of cognitively normal persons and
      carers of people with dementia, in this population. Validated cognitive tests
      were administered to participants drawn from a random sample of all persons
      referred to the North West Hospital Aged Care Assessment Team, and diagnoses of
      dementia were made according to ICD-10 criteria. Available carers were assessed
      for psychological morbidity and burden with the General Health Questionnaire and
      the Zarit Family Burden Interview. Of 100 patients selected, 78 were assessed, of
      whom 34 (44 per cent) were cognitively normal and 34 (44 per cent) fulfilled ICD
      10 criteria for dementia. A further 8 (10 per cent) had cognitive impairment not
      meeting the criteria for dementia. There was a high level of psychological
      morbidity and burden among the carers of both the cognitively normal patients and
      the dementia sufferers, which was largely accounted for by the patients' physical
      disability. This has implication for the adequate provision of health care and
      services to both patients and carers of this population. Adequate education of
      members of aged care assessment teams in the identification of dementia and their
      ability to refer to appropriate dementia-specific services and provide
      counselling for carers requires future planning.

PMID- 7626679
TI  - The effects of partial decriminalisation on cannabis use in South Australia, 1985
      to 1993.
AB  - In 1987 the Cannabis Expiration Notice scheme decreased penalties for the
      personal use of cannabis in South Australia. Data from four National Campaign
      Against Drug Abuse (NCADA) household drug-use surveys covering the period 1985 to
      1993 were analysed to measure the effect of the decriminalisation on cannabis
      use. The main outcomes used were the self-reported prevalence rates of having
      ever used cannabis and current weekly use. Logistic regression was used to
      control for the potentially confounding effects of age and sex. Other outcomes
      were rates of having ever been offered cannabis and willingness to use cannabis
      if offered it. Between 1985 and 1993 the adjusted prevalence rate of ever having
      used cannabis increased in South Australia from 26 per cent to 38 per cent. There
      were also significant increases in Victoria and Tasmania, and to a lesser extent
      in New South Wales. The increase in South Australia was not significantly greater
      than the average increase (P = 0.1). Adjusted rates of weekly use increased
      between 1988 and 1991 in South Australia, but did not change through 1993.
      Although the effect was in the direction of a greater increase in South
      Australia, this was not statistically significant when compared to increases in
      the rest of Australia (P = 0.07). The greatest increase in adjusted weekly use
      occurred in Tasmania between 1991 and 1993, from 2 per cent to 7 per cent.
      Although the NCADA survey data indicate that there were increases in cannabis use
      in South Australia in 1985-1993, they cannot be attributed to the effects of
      partial decriminalisation, because similar increases occurred in other states.

PMID- 7626680
TI  - Domestic violence experienced by women attending an accident and emergency
      department.
AB  - The aim of the study was to establish the extent and severity of domestic
      violence experienced by women attending the accident and emergency department of
      a large teaching hospital in Newcastle. The data were collected over a five-week
      period in 1992. All women between 17 and 80 years, attending the emergency or
      ambulatory areas between 8 a.m. and midnight, were asked to complete a
      confidential structured interview. A total of 401 women participated in the
      study, representing 82 per cent of eligible women approached. Each participant
      was asked if she had ever been physically hurt by someone close to her. Questions
      were asked to determine the relationship to the perpetrator, the type and cause
      of injury, treatment necessary and help sought. Seven (1.7 per cent, 95 per cent
      confidence interval (CI) 0.46 to 3.02) of the women surveyed were attending the
      hospital as a direct result of an incident of domestic violence, and 100 women
      (25 per cent, CI 21 to 29) had experienced domestic violence at some time.
      Bruising, fractures and cuts were the most common forms of injury, with the most
      common locations being the head, face and chest. Weapons, such as guns and
      knives, were used in 20 per cent of the incidents. A considerable number of the
      women (68 per cent) did not seek help at the time of their injuries. As a
      substantial proportion of women have experienced domestic violence in their
      lives, accident and emergency workers should receive training in recognising and
      assisting victims of domestic violence.

PMID- 7626681
TI  - Beliefs and behaviour of general practitioners regarding promotion of physical
      activity.
AB  - To assess current practice, perceived desirable practice and barriers related to
      the promotion of physical activity in general practice, a questionnaire was
      developed and distributed to all 1228 general practitioners in Perth. From these,
      789 valid returns were received (71 per cent response). The mean age of the
      respondents was 45 years, 69 per cent were male, 52 per cent had postgraduate
      qualifications and 73 per cent were in full-time practice. General practitioners
      most frequently asked patients about their current level of physical activity and
      discussed physical activity programs when seeing patients with symptoms of
      conditions that could benefit from exercise, rather than asking all patients, new
      patients or patients previously seen. Walking specifically for fitness was the
      activity most likely to be recommended. General practitioners felt more able to
      offer general advice than specific advice on physical activity. Lack of time was
      reported most frequently as a barrier to the promotion of physical activity (47
      per cent), followed by insufficient educational materials (29 per cent), and
      preference of patients for drug treatment (27 per cent). There were significant
      differences between self-reports of current practice and perceived desirable
      practice in the promotion of physical activity by general practitioners. Future
      strategies should aim to increase the frequency of advice to patients with
      specific health conditions.

PMID- 7626682
TI  - Australian adult smoking prevalence in 1992.
AB  - To estimate the prevalence of smoking among Australian adults in 1992, 6046
      adults aged 16 years and over (3063 men and 2983 women) were interviewed. A large
      market-research firm interviewed the sample, face-to-face in their homes during
      weekends. Overall, 28.2 per cent of men and 23.8 per cent of women were current
      smokers; 32.3 per cent of men and 21.9 per cent of women were past smokers. On
      average, male smokers consumed 22.1 factor-made cigarettes a day and female
      smokers consumed 19.1 cigarettes a day. The daily tar intake was 179 mg for male
      smokers and 131 mg for women. The most popular packet size was 25 (40 per cent of
      smokers) followed by the packet of 50 (17 per cent). Occupational and education
      status were inversely related to smoking prevalence. Men and women with less
      education and men in low-status occupations were more likely to use cigarettes
      from the large packet sizes. Comparison with earlier data suggests that smoking
      prevalence is still declining, with a significant recent drop in female but not
      male smoking prevalence. While in 1992, the prevalence of smoking among women was
      less than that for men, projected estimates suggest that by the year 2001 more
      women than men will smoke.

PMID- 7626683
TI  - Smoking-related beliefs and behaviour of South Australians with diabetes.
AB  - Data cumulated from three representative population surveys (n = 9402) in South
      Australia were used to determine smoking prevalence of those aged 15 years or
      over with and without self-reported medically confirmed diabetes. Overall,
      smoking prevalence in the two groups did not differ. However, among those aged
      under 40 years with self-reported diabetes, smoking prevalence approached 55 per
      cent, which was significantly higher than in young respondents without diabetes
      (32 per cent). Diabetic smokers were no more likely than were nondiabetic smokers
      to have tried to quit or to be ready to quit; one-quarter of diabetic smokers had
      no thought of quitting or of modifying their habit. Smokers with diabetes were
      significantly more likely to be heavy smokers (43.5 per cent) than were
      nondiabetic smokers (23.4 per cent). Fewer smokers with diabetes tended to
      believe that smoking causes or aggravates heart disease or circulatory problems
      than did other smokers, although these differences did not reach statistical
      significance. Additional effort is required to find methods to assist people with
      diabetes to refrain from smoking.

PMID- 7626685
TI  - Using ambulance service records to examine nonfatal heroin overdoses.
AB  - Overdoses are a preventable health hazard associated with heroin use. In the
      first study of its kind, we examined the records on nonfatal overdoses of the
      Australian Capital Territory (ACT) Ambulance Service from August 1990 to July
      1993. There was a dramatic increase in the number of overdoses in the second half
      of 1992 and the first half of 1993, but the reasons for the increase are not
      clear. Most overdoses occurred in men aged under 30, indoors, and many cases were
      taken to hospital. Often there was no information on why the overdose occurred;
      when information was available, about half the cases were attributed to taking
      heroin in combination with other drugs. Suggestions for improving the quality of
      the data collected are made. These include more systematic recording by ambulance
      officers of the drug involved in the overdose and whether the drug was used alone
      or in combination with others, and linkage of ambulance service records with
      survey data and information from analysis of heroin purity.

PMID- 7626686
TI  - Evidence for quiescent S- and G2-phase cells in human colorectal carcinomas: a
      flow cytometric study with the Ki-67 antibody.
AB  - The expression of certain antigens specific for proliferating cells can be
      determined simultaneously with cell cycle distribution by means of two
      dimensional flow cytometry. In this way, a tumour's growth potential is
      characterized more precisely than with any one parameter alone. Here we describe
      such simultaneous measurements of DNA content and labelling with the Ki-67
      antibody that distinguishes between cycling and non-cycling cells. Having
      overcome a number of technical problems we were able to analyse material from 29
      biopsies of human colorectal tumours. In a number of cases, Ki-67 negative cells
      were found with a DNA-content of G0/1 only, whereas all cells with an S- or G2
      phase DNA-content were Ki-67 positive. There were other cases in which cells with
      an S- and G2-phase DNA-content had obviously become quiescent (Ki-67 negative),
      sometimes even outnumbering the proliferating (Ki- 67 positive) cells in the
      respective compartments of the cycle. Generally, however, when Ki-67 negative and
      positive subpopulations were analysed separately it was found that the former had
      a significantly lower (S + G2)-phase fraction than the latter. There was evidence
      for a correlation between Ki-67 index and (S + G2)-phase fraction at least in the
      subgroup of aneuploid tumours. Neither of the two parameters was correlated with
      stage according to Duke's classification or tumour size. However, a positive
      correlation was found between the fraction of unlabelled S- and G2-phase cells
      and tumour size as reflected in the T category.

PMID- 7626684
TI  - Incidental depiction of cigarettes and smoking in Australian magazines, 1990
      1993.
AB  - The study aimed to assess evidence of any increase in apparently incidental
      photographic depictions of cigarettes or smoking in Australian magazines
      following the ban on tobacco advertising in the print media introduced in January
      1991. We examined 27,704 pages in 20 Australian magazines popular among young
      people or aimed at low socioeconomic groups during three sample periods in 1990
      (before the ban), 1991 and 1993 (after the ban). All photographs showing
      cigarettes or smoking were counted and a smoking rate per page was calculated.
      When all 20 magazines were combined, there was a 75 per cent increase in the rate
      of photographs of smoking per page from 1990 (six months before the ban) to 1991
      (six months after the ban). However, there was a reduction of 36 per cent in the
      rate of smoking photographs per page between 1991 and 1993 (18 months after the
      ban) and a nonsignificant increase of 12 per cent across the three sample
      periods. Photographs of smoking are infrequent in Australian magazines (mean:
      1:147 pages, range: 1:17 pages to zero). There appears to be a commendable
      constraint by many Australian magazine editors in limiting the publication of
      photographs that show smoking or cigarettes. Some magazines never show smoking,
      indicating that a goal of total absence of photographs of smoking is achievable.
      Some magazines have room for improvement.

PMID- 7626687
TI  - Nucleolin and fibrillarin expression in stimulated lymphocytes and
      differentiating HL-60 cells. A flow cytometric assay.
AB  - Nucleolin and fibrillarin are two histone-like major proteins in the nucleolus
      that were found to be overexpressed in proliferating cells. Using specific
      antibodies to either nucleolin or fibrillarin flow cytometric, measurements were
      carried out to demonstrate quantitative changes of these proteins during
      lymphocyte mitogenic activation and differentiation of HL-60 promyelocytic
      leukaemia cells. The expression of nucleolin increased during lymphocyte
      stimulation and decreased slowly but constantly in the course of differentiation
      of HL-60 cells. Expression of fibrillarin reached a maximum in the first cell
      cycle and then dropped to a basic level in stimulated lymphocytes. Compared to
      nucleolin, the level of fibrillarin decreased more rapidly and more extensively
      in differentiating HL-60 cells. The data support other observations that
      nucleolin is a stabile structural protein at the ribosomal genes while
      fibrillarin may have a more specific functional role in nucleologenesis and
      ribosome production.

PMID- 7626688
TI  - Threshold expression of cyclin E but not D type cyclins characterizes normal and
      tumour cells entering S phase.
AB  - Complexes of cyclin-dependent kinases (cdk) and their partner cyclins drive the
      cell through the cell cycle, each such complex phosphorylating a distinct set of
      proteins at a particular check-point or phase of the cycle. Immunocytochemical
      detection of cyclins combined with measurement of cellular DNA content by flow
      cytometry makes it possible to relate expression of each of these proteins with
      the actual cell cycle position, without the necessity of cell synchronization. In
      the present study, we have investigated expression of E and D type cyclins in G1
      cells and in cells entering S phase, in eight different human hematopoietic and
      solid tumour cell lines (two leukaemias, a lymphoma, three breast carcinomas, a
      colon carcinoma and a bladder transitional cell carcinoma) during their
      exponential phase of growth, as well as in normal mitogen stimulated lymphocytes.
      In all the cell types studied, the average level of D type cyclin expression was
      invariable throughout the cell cycle. A great intercellular variability, in
      particular of the G1 cell subpopulations, and the presence of a large fraction of
      G1, S and G2 + M cells that were cyclin D negative (20-40% in tumour cell lines
      and about 80% among lymphocytes), were other characteristic features of D type
      cyclin expression. In contrast to D type cyclins, the expression of cyclin E was
      discontinuous during the cycle, peaking at the time of cell entrance to S. Also,
      a well defined threshold in expression of cyclin E characterized cells that were
      entering S phase, and virtually no cyclin E negative cells were seen during the
      early portion of S phase. The data indicate that while cell entrance to S phase
      is unrelated to expression of D type cyclins (at the time of entrance),
      accumulation of cyclin E up to critical level is a prerequisite for initiation of
      DNA replication. The great intercellular variability in expression of D type
      cyclins and their invariant average level across the cell cycle suggest that
      these cyclins, in addition to their acknowledged function in promoting cell
      progression through mid- to late-G1 may have other role(s), related or unrelated
      to the cell cycle progression. The presence of a large number of D type cyclin
      negative cells in all phases of the cycle suggests that during exponential growth
      the cells may not express this protein and yet may traverse the cycle, including
      G1 phase.

PMID- 7626689
TI  - Regrowth resistance in cancer: why has it been largely ignored?
AB  - In drug-sensitive malignancies, treatment failure is a complex phenomenon
      resulting from both drug resistance and the rapid regrowth of malignant cells in
      between cycles of chemotherapy. This phenomenon has been referred to as regrowth
      resistance, and has been identified as a common impediment to the successful
      treatment of many neoplastic diseases. This phenomenon has received little
      attention in the past. The administration of maximally tolerated individual
      dosages of chemotherapeutic agents, combined with the use of biological response
      modifiers to slow the regrowth between courses of therapy, would be an effective
      approach to reduce the regrowth resistance. This also could reduce the emergence
      of drug resistant clones.

PMID- 7626690
TI  - Who cares about the stability of analytes?

PMID- 7626691
TI  - Markers for vulnerability in acute porphyria. A hypothesis paper.
AB  - Previously symptomatic and permanently asymptomatic carriers of a gene mutation
      for acute intermittent porphyria as well as matched controls were screened with
      regard to a series of variables of possible relevance to the development of
      porphyric symptoms. The basis for the study was a concept of acute porphyria as a
      condition of a permanent system overload of oxidative stress, with long term
      effects on hepatic and renal tissue, and with instances of periodic overload of
      free radicals giving rise to acute neurologic involvement. Leukocyte
      concentrations of manganese, calcium, iron and zinc, as well as erythrocyte
      calcium differed between the groups, acute intermittent porphyria gene carriers,
      irrespective of previous porphyric illness, showing significantly higher levels
      than the controls. Manganese was found to be the most discriminative component of
      all the 78 variables investigated, accounting for about 98 per cent of the
      variance between the groups. An increment, by a factor of four, in cellular
      manganese is suggestive of an increase, in acute intermittent porphyria, of a
      manganese associated enzyme, e.g. glutamine synthetase, pyruvate carboxylase or
      mitochondrial superoxide dismutase. The best fit into the model considered is
      provided by a theory focused on superoxide dismutase, induced in response to
      superoxide anion radical produced from aminolaevulinic acid. In porphyria gene
      carriers seemingly resistant to porphyric manifestations, an increase in
      potentially prooxidant cellular iron is matched by a proportional increment in
      manganese, i.e. presumably by a corresponding mitochondrial superoxide dismutase
      induction. This mechanism is not operative in porphyric individuals prone to
      development of neuropsychiatric symptoms. In acute intermittent porphyria with a
      history of porphyric illness there is a positive correlation between erythrocyte
      manganese and serum folate and a negative correlation between leukocyte
      ferrochelatase activity and serum cobalamin concentration. This may mirror a role
      of the cobalamin-folate system in the acute porphyric process.

PMID- 7626692
TI  - Determination of the glomerular filtration rate by identification of sinistrin
      kinetics.
AB  - A computer-based method of system identification and estimation of parameter
      variance for two-compartment models matched to dynamic sinistrin concentration
      profiles for the determination of glomerular filtration rate is described.
      Thereby a procedure for the judgment of the optimal sampling time horizon is
      presented. Since single-injection techniques are suspected of yielding systematic
      overestimation of the glomerular filtration rate, a method is demonstrated
      confirming that such a technique employing sinistrin kinetics can be used to
      correctly determine the glomerular filtration rate. The validation of the system
      parameters gained by the single-injection method is made through prediction of
      the concentration contour under a constant infusion regimen in the same subject
      on a different occasion. This was performed in healthy controls and in patients
      with various degrees of renal insufficiency. Upon consideration of the dependence
      of the clearance estimates and their variances on the protocol duration in test
      subjects examined from four to ten hours, an adaptive design of the protocol
      length is developed.

PMID- 7626694
TI  - Haemostasis activation markers in plasma of patients with benign and malignant
      gynaecological tumours: a pilot study.
AB  - Coagulation and fibrinolysis activation have been investigated in fifty-eight
      women with recently detected gynaecological tumours. Twenty-six were benign and
      32 malignant: of the last group nine patients had metastases. A control group
      consisted of 31 age-matched healthy women. Prothrombin fragment 1 + 2, thrombin
      antithrombin III and D-dimer were measured. The median values of all analytes
      were significantly higher in the malignant tumour group, but not in the benign
      tumour group, as compared to the control group. The group of patients with a
      gynaecological tumour and metastases differed from the non-metastasized tumour
      group in prothrombin fragment 1 + 2, thrombin-antithrombin III and D-dimer. In
      the non-metastasized malignant tumour group solely prothrombin fragment 1 + 2 was
      significantly higher than in the benign tumour group. Coagulation and
      fibrinolysis predominating as can be derived from the elevated D-dimer/thrombin
      antithrombin III and D-dimer/prothrombin fragment 1 + 2 ratios. The studied
      constituents do not enable a differentiation between the benign and malignant
      processes. However, as the differences of these values in both malignant tumour
      groups were significant, this might be used to trace the existence of metastases
      in gynaecological tumours. Investigation of these analytes in several specific
      types of gynaecological tumours might be clinically relevant.

PMID- 7626693
TI  - Extracellular matrix proteins as early markers in diabetic nephropathy.
AB  - Basement membrane thickening and mesangial expansion characterize the renal
      involvement in diabetes mellitus and precede any symptoms of renal dysfunction,
      e.g., albuminuria and changes in glomerular filtration rate. Since the
      morphological changes can only be diagnosed by biopsy, this study was designed to
      investigate whether the urinary excretion of renal extracellular matrix proteins
      might reflect the morphological alterations. To specify the extent of renal
      involvement in diabetes, the patients, type I as well as type II diabetics, were
      classified according to their urinary albumin excretion: normal albumin excretion
      below 30 micrograms/min, microalbuminuria from 30 to 300 micrograms/min, and
      overt albuminuria above 200 micrograms/min. Laminin, collagen IV, and
      fibronectin, all intrinsic components of the renal extracellular matrix, were
      determined in serum and urine by radioimmunoassay or enzyme-linked-immunosorbent
      assay, respectively. The results are given as median values (mean). Additionally,
      the urinary fragment pattern of fibronectin was analysed qualitatively by
      immunoblotting. Laminin concentrations in serum and in urine did not change in
      diabetics. Collagen IV decreased in serum of patients with increased albumin
      excretion (controls: mean = 255 micrograms/l, normoalbuminuric patients: mean =
      56 micrograms/l, microalbuminuric patients: mean = 52 micrograms/l, and patients
      with overt albuminuria: mean = 70 micrograms/l; alpha < 0.01) and increased in
      urine (controls, normoalbuminuric and microalbuminuric patients: not detectable,
      patients with overt albuminuria: mean = 5 ng/12 h; apha < 0.001).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7626695
TI  - Storage of serum or whole blood samples? Effects of time and temperature on 22
      serum analytes.
AB  - Information on the stability of serum analytes during storage of serum or whole
      blood samples is often incomplete and sometimes contradictory. Using a widely
      available analyser (Hitachi 737/Boehringer), we therefore determined the effects
      of storage time and temperature on the measured concentrations of the following
      serum analytes: sodium, potassium, calcium, chloride, inorganic phosphate,
      magnesium, creatinine, urea, uric acid, bilirubin, cholesterol, HDL- and LDL
      cholesterol, triacylglycerols, creatine kinase, aspartate aminotransferase,
      alanine aminotransferase, gamma-glutamyltransferase, alkaline phosphatase, alpha
      amylase, lactate dehydrogenase and cholinesterase. When separated serum was
      stored at + 9 degrees C for seven days, the mean changes in inorganic phosphate
      and lactate dehydrogenase exceeded significantly (p < 0.05 or 0.001,
      respectively) the maximum allowable inaccuracy according to the Guidelines of the
      German Federal Medical Council; all other quantities were sufficiently stable. In
      serum at room temperature, inorganic phosphate, uric acid, HDL-cholesterol and
      triacylglycerols increased continuously, whereas bilirubin, LDL-cholesterol,
      creatine kinase and aspartate aminotransferase decreased more than the guidelines
      permit during the storage period (p < 0.05 for aspartate aminotransferase, p <
      0.001 for the other analytes mentioned). In whole blood stored for 7 days at + 9
      degrees C, only the following serum analytes satisfied the stability requirements
      of the guidelines: calcium, urea, cholesterol, HDL-cholesterol, LDL-cholesterol,
      triacylglycerols, creatine kinase, gamma-glutamyltransferase and cholinesterase.
      When stored at room temperature, only sodium, uric acid, bilirubin, cholesterol,
      triacylglycerols, aspartate aminotransferase, alanine aminotransferase, alkaline
      phosphatase, alpha-amylase and cholinesterase were still stable after 3 days. The
      data collected show that all quantities examined are sufficiently stable for four
      days in separated serum stored at + 9 degrees C.

PMID- 7626696
TI  - Diagnostic analysis of total protein, albumin, white cell count and differential
      in ascitic fluid.
AB  - Accurate and precise procedures are described for the measurement of total
      protein, albumin, white cell count and differential in ascitic fluid. The total
      protein method (biuret) on the serum chemistry analyser, Bayer-Technicon Chem-1,
      was calibrated against the biuret reference method in the measuring range from 1
      100 g/l, covering serum as well as ascitic fluid values. The albumin method
      (bromcresol green) on the Chem-1 was calibrated for the measurement range from 1
      50 g/l against the new human plasma protein international reference preparations
      and compared to the nephelometric method on the Beckman Array, which was also
      calibrated against these reference preparations. A good correlation was obtained
      for total protein between the Chem-1 (y) and the biuret reference method (x) in
      58 ascitic fluids (y = 1.02x -0.3; r = 1.00). A good correlation between the Chem
      1 (y) and the Array (x) was also obtained for albumin (r = 0.99). The bromcresol
      green method, however, which is not fully specific, resulted in significantly
      higher results (y = 1.32x - 1.3). The immunochemical procedure is considered the
      more accurate and therefore the bromcresol green method is not suitable for the
      determination of albumin in ascitic fluids. The white cell count in ascitic fluid
      can be measured reliably by most haematology analysers if the sample is fresh and
      homogeneous, but the differential is flagged as a result of differing morphology.
      Handmade smears from ascitic fluid, however, show uneven distribution of cells
      and disturbed morphology.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7626697
TI  - Screening for oligoalbuminuria by means of Micral-Test II. A new immunological
      test strip.
AB  - A new dip-and-read test strip for systematic detection of oligoalbuminuria was
      assessed. The test is based on a competition for gold-labelled anti-albumin
      antibodies between specimen albumin and albumin molecules immobilised in the test
      strip. The final detection area is coloured by excess free antibodies. The colour
      reaction is compared to a colour scale reflecting 0, 20, 50 and 100 mg/l albumin.
      Method comparison with an immuno-turbidimetric quantitative technique was
      performed on 747 unselected specimens. The correlation coefficient was 0.938, the
      Spearman rank coefficient 0.863. In spite of considerable overlap of the results
      attributed to the 4 colour blocks, the test was found to be perfectly useful as a
      2-class-test, as there were practically no false negative tests and as all the
      specimens yielding reactions stronger than the 20 mg/l colour block were found to
      contain 20 mg/l albumin or more by the reference method. The colour block 20 mg/l
      represents the inevitable grey zone, results in this range being found to be
      normal and increased above this pathological cut-off by the reference method.
      Follow-up by quantitative albumin dosage in timed morning urine for all specimens
      found positive by the dipstick confirms the existence of oligoalbuminuria,
      eliminating the cases of orthostatic albuminuria, of oligoalbuminuria simulated
      by low diuresis and the false positives due to oversensitivity of the test strip.
      The test strip is easy to handle. The reaction time is short and the colour
      reaction is stable and easy to read. Systematic use of this test in routine urine
      chemistry is suggested.

PMID- 7626699
TI  - Cell-specific localization of apolipoprotein E messenger ribonucleic acid in the
      testis and epididymis of the rat.
AB  - Apolipoprotein (apo) E, a 35-kDa protein found on the surface of several
      lipoproteins, has been detected in many peripheral tissues and is postulated to
      function in facilitating the transfer of cholesterol/lipids between cells. We
      examined the expression of apo E mRNA in the testes and epididymides of juvenile
      rats (21 days old), prepubescent rats (34-36 days old), and sexually mature rats
      (75-80 days old). In situ hybridization using 35S-labeled rat apo E riboprobes
      was used to identify cells containing apo E mRNA. Such cells were located in the
      interstitial area of testes obtained from rats of all ages. This cell population
      consisted of primarily Leydig cells with occasional macrophages, according to
      immunoreactivity to 3 beta-hydroxysteroid dehydrogenase and antimacrophage
      antibodies, respectively. Caput epididymides obtained from sexually mature and
      prepubescent rats contained apo E mRNA-positive cells located in the basal region
      of the epididymal tubules and within the interstitial stroma. Our data are
      consistent with the concept that locally produced apo E plays a role in the
      physiologic function of the rat testis and epididymis.

PMID- 7626700
TI  - Protein synthesis and secretion by the rat caput epididymidis in vivo: influence
      of the luminal microenvironment.
AB  - The role of intraluminal factors in regulating the functions of the epididymal
      epithelium is unknown and virtually unexplored. Simultaneous in vivo
      microperfusion and microperfusion procedures were carried out on rat caput
      epididymal tubules to examine the effects of the intraluminal microenvironment on
      protein synthesis and secretion. Caput tubules were perifused with 35S-methionine
      for 3 h while the tubule lumen was subjected to a stop-flow perfusion of either
      native caput content from another epididymis (NCC), artificial caput fluid
      containing no testicular factors (ACF), or rete testis fluid (RTF). Protein
      synthesis and secretion were measured quantitatively as trichloroacetic acid-
      (TCA) precipitable 35S-methionine-labeled proteins (cpm/microliter) and
      qualitatively as autoradiograms of electrophoresed 35S-methionine-labeled
      proteins. Electrophoresed proteins, i.e., those in fluids collected by
      micropuncture, were: perifused interstitial fluid (IF), lumen fluid from the
      perifused but not perfused length of tubule (LF), and the perfusion fluid (PF) re
      collected from the tubule lumen. Undiluted tubule extract (TE) of the perfused
      length of tubule was also analyzed. ACF in the lumen caused a significant
      reduction in proteins synthesized and secreted by the epithelium, and RTF in the
      lumen returned protein synthesis and secretion to control values. For example,
      TCA-precipitable 35S-methionine-labeled proteins in TE of tubules perfused with
      NCC, ACF, or RTF were 107.6 +/- 13.1, 58.9 +/- 6.9, and 121.9 +/- 19.7 x 10(3)
      cpm/microliters, respectively. Autoradiograms reinforced this data. Subsequently,
      tubules were perfused with ACF or ACF containing physiological concentrations of
      sex hormone-binding globulin (SHBG; an androgen-binding protein [ABP] homolog), 5
      alpha-dihydrotestosterone (DHT), or SHBG+DHT.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7626698
TI  - International Federation of Clinical Chemistry (IFCC). Scientific Division.
      Committee on pH, Blood Gases and Electrolytes. Approved IFCC recommendations on
      whole blood sampling, transport and storage for simultaneous determination of pH,
      blood gases and electrolytes.
AB  - Pre-analytical variables, e.g., specimen collection, transport, and storage, can
      contribute significantly to inaccurate pH, blood gas, and electrolyte values. The
      International Federation of Clinical Chemistry (IFCC), through its Committee on
      pH, Blood Gases and Electrolytes, has developed specific recommendations to
      minimize the undesirable effects of pre-analytical variables. The Committee has
      drawn upon the experiences of its own members as well as published data by
      others. Specifically, the Committee has included pertinent guidelines and
      suggestions by the IFCC Working Group on Selective Electrodes (WGSE), the
      National Committee on Clinical Laboratory Standards (NCCLS), and the
      Electrolyte/Blood Gas Division of the American Association for Clinical Chemistry
      (AACC). This paper will familiarize the reader with the effect of different types
      of specimen containers and anticoagulants. It discusses important aspects of
      specimen collection procedures including patients status and special precautions
      during specimen collection from indwelling catheters or cannulae. The paper also
      identifies different requirements in storage and transport of specimens for blood
      gas and electrolyte analysis.

PMID- 7626701
TI  - Bovine cyclic endometrium contains high-affinity luteinizing hormone/human
      chorionic gonadotropin binding sites.
AB  - High-affinity LH/hCG binding sites have been characterized in porcine, lepine,
      and murine uteri. In the present study, LH/hCG binding sites were characterized
      in bovine endometrium. Radioreceptor assays were performed with membrane
      homogenates of endometrial tissues and analyzed for binding site specificity and
      capacity. There was little competition for receptor occupancy between hCG and
      ovine FSH (5%) or ovine prolactin (< 0.1%), but there was a 20% cross-reaction
      with eCG. There was no affinity for LH/hCG in crude membrane preparations of
      kidney, skeletal muscle, or vascular tissues. Concentrations of endometrial
      LH/hCG binding sites were determined during the bovine estrous cycle. LH/hCG
      receptors were found in cell preparations from Days 2-4 and 15-17 of the cycle,
      but not in preparations from the other stages of the cycle tested (Days 8-12, pre
      and post-estrus, and ovulation). The concentration of uterine LH/hCG receptor
      varied during the estrous cycle, with higher values at Days 15-17 (3.1 fmol/mg
      protein) and lower values at Days 2-4 (1.2 fmol/mg protein). However, the binding
      capacity of hCG by luteal cells (9.7 fmol/mg protein) was 3-fold higher (p <
      0.01) than that by endometrial tissue on any day studied. No differences in
      affinity constant (Ka) were seen between endometrial LH/hCG receptors (either)
      from Days 2-4 or 15-17) and mid-cycle luteal cells (0.60 x 10(11) M-1). Using
      Western blot analysis, we determined the expression of cyclooxygenase (COX)
      during the estrous cycle of the cow. It was found that the signal for COX was
      strongest at 15-17 days.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7626702
TI  - Regulation of transforming growth factor alpha gene expression in an ovarian
      surface epithelial cell line derived from a human carcinoma.
AB  - The surface epithelium plays an important role in normal ovarian physiology: the
      cells proliferate in the vicinity of the developing preovulatory follicle to
      accommodate the increase in follicular size, and to repair the surface after
      ovulation. These bouts of mitotic activity in vivo must be strictly regulated by
      the activity of growth factors and their receptors. Since transforming growth
      factor alpha (TGF alpha) has been identified as a growth-promoting factor for
      normal surface epithelial cells from human ovaries and ovarian surface epithelial
      cell lines, we have examined the regulation of the TGF alpha gene in HEY cells, a
      surface epithelial cell line derived from a human ovarian carcinoma. Treatment of
      HEY cells for 60 h with estradiol-17 beta, dihydrotestosterone, or progesterone
      at concentrations ranging from 5 x 10(-8) to 5 x 10(-6) M did not influence the
      level of the 4.5-kb transcript for TGF alpha. Treatment of HEY cells with TGF
      alpha increased the steady-state levels of TGF alpha mRNA, indicating that an
      autoregulatory mechanism could result in overexpression of TGF alpha. TGF beta, a
      known growth inhibitor of ovarian surface epithelial cells, decreased the steady
      state levels of TGF alpha mRNA, suggesting a mechanism by which the levels of TGF
      alpha and mitotic activity could be regulated. HEY cells, like the human surface
      epithelial cells from which they were derived, were found by quantitative
      polymerase chain reaction (PCR) to contain TGF beta 1 mRNA. The TGF beta 1 mRNA
      was translated into immunoreactive TGF beta 1, indicating that TGF beta can act
      in an autocrine manner. By use of quantitative PCR, HEY cells were shown to
      express the genes for the TGF beta receptor II, betaglycan and endoglin. By cross
      linking, these components of the TGF beta receptor system were found to bind TGF
      beta 1. This is the first demonstration of expression of functional TGF beta
      receptors in HEY cells and represents the first demonstration in an ovarian cell
      system. In summary, our findings suggest that the levels of TGF alpha and the
      cell growth of normal and transformed surface epithelial cells from human ovaries
      may be regulated by the interaction of autoregulatory mechanisms involving TGF
      alpha and TGF beta ligand-receptor systems.

PMID- 7626703
TI  - Expression of apolipoprotein J in the uterus is associated with tissue
      remodeling.
AB  - The endometrium is a dynamic tissue that, in response to hormonal cues, undergoes
      cycles of growth and involution. Extracellular factors required for this
      remodeling are poorly understood. The potential role in endometrial turnover of
      apolipoprotein J (apoJ), a secretory glycoprotein that can bind lipids and
      membrane-active proteins, is proposed on the basis of its spatial and temporal
      patterns of expression during normal cycling, after ovariectomy, and in response
      to hormone manipulation. In the mouse, apoJ mRNA was expressed in uterine luminal
      and glandular epithelial cells coincident with the presence of apoJ protein. The
      apoJ gene was differentially expressed in the glandular and uterine luminal
      epithelial cells during the estrous cycle and following hormone depletion.
      Expression of apoJ was not induced in ovariectomized mice by estrogen,
      progesterone, or dexamethasone treatment alone. Progesterone administration after
      an initial estrogen pretreatment, however, resulted in dramatic induction of apoJ
      as the progesterone level declined. In contrast, apoJ was not induced when a long
      lived progesterone analog, medroxyprogesterone, was substituted for progesterone.
      In the human menstrual cycle, apoJ was present in glandular lumens only during
      the late secretory phase. Declining progesterone levels, causing substantial
      tissue reorganization, are characteristic of the times of marked apoJ induction
      in uterine epithelial cells. These expression patterns are consistent with apoJ
      functioning as an extracellular cytoprotectant by mediating clearance of and/or
      neutralizing cytolytic tissue debris.

PMID- 7626704
TI  - Prostaglandins mediate the stimulation of deoxyribonucleic acid synthesis by
      transforming growth factor alpha in hen granulosa cells during ovarian follicular
      development.
AB  - The present study was an examination of the possible involvement of specific
      membrane lipid metabolites of prostaglandins (PGs), leukotrienes (LTs),
      lysophosphatidic acid (LPA), and lysophosphatidyl choline (LPC) in transforming
      growth factor alpha-(TGF alpha) induced DNA synthesis by granulosa cells during
      follicular development. Granulosa cells from the first (F1) and the fifth and
      sixth (F5-6) largest preovulatory follicles were cultured for 18 h in the
      presence of TGF alpha and/or an inhibitor of either phospholipase A2 (PLA2),
      cyclooxygenase, or lipoxygenase, LTs, LPA, LPC, and/or PGs. TGF alpha-induced,
      but not basal, DNA synthesis in F1 and F5-6 granulosa cells was suppressed by
      inhibitors of PLA2 and cyclooxygenase but not of lipoxygenase. The inhibition was
      concentration-dependent and could be attenuated by exogenous PGE2. Likewise, PGF
      and PGE production was suppressed by these inhibitors. Moreover, PGE2 and, to a
      lesser extent, PGF2 alpha increased basal [3H]thymidine incorporation and
      enhanced DNA synthesis induced by a submaximal stimulatory concentration of TGF
      alpha. The mitogenic effect of PGs was more evident in granulosa cells from F5-6
      follicles than in those from F1 follicles. In contrast, LTs (LTB4, LTC4, LTD4),
      (+)5(s)-hydroxy-(6E,8Z,11Z,14Z)-eicosatetraenoic acid (5-HETE), and
      lysophospholipids (LPA and LPC) had no effect on granulosa cell DNA synthesis,
      irrespective of the stage of ovarian follicular development and the presence of
      TGF alpha and PGE2. These studies demonstrate that 1) arachidonic metabolites of
      cyclooxygenase, but not lipoxygenase pathway and arachidonate lysophospholipid by
      products (LPA and LPC), are involved in the regulation of granulosa cell DNA
      synthesis by TGF alpha; 2) compared to PGs of the F series, PGE2 and PGE1 are
      more effective in either mimicking the action of TGF alpha or potentiating the
      mitogenic response of the cells to the growth factor; and 3) the DNA synthetic
      response of the hen granulosa cell to PGs is greater in granulosa cells from F5-6
      than in those from F1 follicles. These findings are consistent with our concept
      that an increase in PG production is a necessary element in the TGF alpha
      regulated cascade of biochemical events leading to chicken granulosa cell
      mitogenesis during hen ovarian follicular development.

PMID- 7626705
TI  - Androgen regulation of an elastase-like protease activity in the seminal vesicle.
AB  - The processing of secretory proteins in the guinea pig (GP) seminal vesicle
      epithelium (SVE) is altered by castration and restored by treatment of animals
      with androgens. To test the hypothesis that the changes in protein processing are
      due to changes in the activity of specific proteases, we examined the GPSVE for
      protease activities capable of cleaving a synthetic elastase substrate, succinyl
      alanyl-alanyl-alanyl-p-nitroanilide (Suc(Ala)3pNA). We found that the GPSVE does
      contain a Suc(Ala)3pNA-cleaving activity that is sensitive to the serine protease
      inhibitor diisopropylfluorophosphate (DFP) and to the elastase inhibitor
      elastatinal. Furthermore, the amount of protease activity per milligram of SVE
      protein is reduced to about 50% of control levels by castration. The activity is
      completely restored within four days by treatment of castrated animals with
      androgens, but is not restored by treatment with estradiol, progesterone, or
      dexamethasone. Although the SVE enzyme did not yield a pattern of specific
      cleavage products when incubated with a secretory protein substrate in vitro,
      this enzyme activity was competitively inhibited by a peptide whose primary
      sequence included the cleavage site used by the processing machinery in vivo.

PMID- 7626706
TI  - Molecular localization of free thiols in human sperm chromatin.
AB  - The presence in human sperm nuclear proteins of a limited amount of unoxidized
      thiol groups, stabilized by reversible binding to zinc ions, has been presumed to
      play a role in the decondensation of sperm within the oocyte. In the present
      study, the number and molecular localization of free sulfhydryls in the major
      proteins of human sperm chromatin, protamines P1 and P2, were determined by
      alkylation of reactive thiols with 14C-iodoacetamide, isolation of protamines,
      and peptide mapping. Less than 1.5% of the cysteines of protamines were found as
      reactive thiols, a proportion strikingly lower than that reported previously for
      whole human sperm proteins. The amount of sulfhydryls was unaffected by the zinc
      chelating agent EDTA. Labeling was evenly distributed on every cysteine of
      protamines P1 and P2. The results confirm the extensive stabilization of sperm
      chromatin by disulfide bridges and show that the unoxidized cysteines remaining
      at the end of epididymal transit in some protamine molecules may be one of the
      six (protamine P1) or five (protamine P2) cysteines present in the sequence of
      each class of protamines. This even distribution of the reactive cysteines could
      facilitate decondensation of sperm nuclei initiated by a thiol-disulfide
      exchange.

PMID- 7626707
TI  - Reproductive success of female rainbow trout (Oncorhynchus mykiss) in response to
      graded dietary ascorbyl monophosphate levels.
AB  - Ascorbic acid is an essential nutrient in rainbow trout diets and has been shown
      to play an important role in fish reproduction. Recommended dietary levels are
      based on immature fish, and the specific requirements for brood stock are
      unknown. To establish the optimum dietary level for mature rainbow trout, six
      graded levels of ascorbyl-2-monophosphate were fed to groups of female fish over
      a period of 10 mo until spawning. Increasing dietary levels of ascorbyl
      monophosphate resulted in significantly increased ascorbic acid concentrations in
      liver, kidney, ovaries, and ovulated eggs. Liver and egg concentrations were
      saturable at 109.3 and 266.6 micrograms ascorbic acid/g tissue, respectively.
      Tissue saturation levels of 83.7% and 91.2%, respectively, were reached at the
      highest dietary level (870 mg ascorbyl monophosphate/kg diet) tested. Both
      fecundity and embryo survival increased significantly with dietary ascorbyl
      monophosphate levels. The results indicated that the present National Research
      Council recommended dietary level of 50 mg ascorbic acid/kg diet for rainbow
      trout is inadequate for brood stock fish. An amount 8 times higher is necessary
      to optimize tissue ascorbic acid levels and achieve maximum reproductive success.

PMID- 7626708
TI  - Immunohistochemical localization of 3 beta-hydroxysteroid dehydrogenase and P450
      17 alpha-hydroxylase during follicular and luteal development in pigs, sheep, and
      cows.
AB  - Follicular and luteal morphology and steroidogenic function were investigated by
      immunohistochemistry for cytochrome P450 17 alpha-hydroxylase (P450c17) and 3
      beta-hydroxysteroid dehydrogenase (3 beta-HSD) during the estrous cycle in pigs,
      sheep, and cows. The theca interna of all species expressed P450c17 during
      follicular development. In the pig, this constituted a continuous layer of cells
      around the follicle, but a sheath of cells lining the basement membrane appeared
      not to express P450c17. Neither was expression of P450c17 in ovine and bovine
      follicles uniform throughout the theca interna. In these two species, a beaded
      appearance was given by P450c17, since it was expressed in some regions but not
      in others. Therefore, staining for P450c17 defined functional sub-populations of
      cells within the theca interna of pigs, sheep, and cows. Ovulation was associated
      with a decrease in P450c17 in all species, but some expression persisted in theca
      derived cells of developing and mature porcine CL. Expression of 3 beta-HSD in
      the preovulatory follicle was confined to the theca of the pig and sheep; in
      contrast, in the cow, it was highest in the granulosa. In general, 3 beta-HSD
      expression appeared to be greater in porcine than ovine or bovine follicles, the
      physiological relevance of which is discussed. Porcine and ovine theca continued
      to express 3 beta-HSD after ovulation, and granulosa-derived cells increased
      their 3 beta-HSD expression markedly as they luteinized in all three species.
      During early luteal development in pigs and sheep, theca-derived cells with high
      3 beta-HSD encircled luteal lobules, but these cells appeared throughout the
      parenchyma of the mature CL. Luteal regression in sheep and cows was typified by
      the loss of many cells expressing 3 beta-HSD, whereas others, adjacent to them,
      appeared to be intact without loss of enzyme expression. These data further
      define differences in steroidogenesis during follicular and luteal development
      among the pig, sheep, and cow.

PMID- 7626709
TI  - Expression of the small proteoglycans biglycan and decorin in the adult human
      testis.
AB  - The genes coding for the core proteins of the small chondroitin sulfate/dermatan
      sulfate proteoglycans (PGs) biglycan and decorin are both expressed in the adult
      human testis. Northern hybridization of human testicular mRNA indicated the
      presence of one specific transcript for biglycan at 2.6 kb and two specific
      transcripts for decorin at 1.6 kb and 1.9 kb. In situ hybridization localized the
      mRNA for biglycan to the peritubular tissue as well as to the tunica muscularis
      and adventitia of arteries. Leydig cells and cells of the seminiferous epithelium
      both proved to be negative. For decorin mRNA, strong signals were found over
      single, dispersed interstitial cells (possibly fibroblasts), the adventitious
      layer of large arteries, and the perivascular tissue cells of small arteries,
      arterioles, and capillaries. In the peritubular cell layers, decorin gene
      expression was comparably lower and was restricted to the outer fibroblast
      layers. Germ cells and Sertoli cells were devoid of any positive signal.
      Immunoblot analysis using specific antisera directed against the core proteins of
      biglycan and decorin confirmed their presence in chondroitin ABC lyase-treated
      proteinaceous extracts of the human testis. Immunohistochemistry for biglycan
      showed a good spatial correlation with the in situ hybridization data and
      revealed in addition a nonuniform distribution of the antigenic material, which
      was located predominantly over peritubular myoid cells and the adventitious layer
      of arteries. Together these results indicate that the expression of both genes in
      the human testis is differentially regulated, despite the overall similarity of
      their protein products, and suggest distinct roles for these PGs in testicular
      function.

PMID- 7626710
TI  - Effect of heat stress on follicular development during the estrous cycle in
      lactating dairy cattle.
AB  - In this study we examined, in two experiments, patterns of follicular development
      and dominance under conditions of heat stress. Estrous cycles were programmed to
      include two follicular waves (wave 1 and 2). On Day 1 of the estrous cycle (Day 0
      = estrus), cows were assigned randomly to cooled (C; n = 6) or heat-stressed (H;
      n = 6) groups. In experiment 1, on Day 12 prostaglandin (PG) F2 alpha was
      injected and a controlled intravaginal drug release device (1.9 g progesterone)
      was inserted (this was removed on Day 17). In experiment 2, PGF 2 alpha was
      injected on Day 14. Ovarian structures were examined daily by ultrasonography,
      and blood samples were collected at each scanning. Cycle lengths were 20 and 17
      days in experiments 1 and 2, respectively. Mean maximal body temperatures were
      higher (p < 0.01) in H (40.3 degrees C) than in C (38.8 degrees C) cows. In
      experiment 1, the rate of increase in number of large follicles (> or = 10 mm)
      was greater in H than in C cows (p < 0.01), resulting in 53% more large follicles
      in H cows during wave 1; this was associated with a lower (p < 0.05) number of
      medium-sized (6-9 mm) follicles between Days 7 and 10 of the cycle. Heat stress
      hastened (p < 0.02) the decrease in size of the first-wave dominant follicle and
      hastened (p < 0.01) the emergence of the second dominant (preovulatory) follicle
      by 2 days.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7626711
TI  - Regulation of luteinizing hormone-releasing hormone (LHRH) secretion by melatonin
      in the ewe. I. Simultaneous delayed increase in LHRH and luteinizing hormone
      pulsatile secretion.
AB  - This study was performed to test the hypothesis that a short-day-like melatonin
      treatment would induce simultaneous stimulations of LHRH and LH secretion.
      Simultaneous serial samples of jugular and portal blood to assay LH and LHRH,
      respectively, were carried out at three different periods according to the
      expected changes in LH secretion. Twenty-six ovariectomized ewes bearing a
      subcutaneous implant of estradiol and exposed to a long-day photoperiod (16L:8D)
      received s.c. implants of melatonin on Day 0. LHRH and LH pulsatile secretion was
      studied in the first group during inhibition of LH secretion by long days (on Day
      -1, n = 6). A second group (n = 9) was sampled on Day 39. Moreover, seven animals
      from this group were sampled on Day 46 to focus on the beginning of LH increase.
      The third group (n = 6) was sampled during maximal LH secretion (Day 74, n = 6).
      A fourth group (n = 5) composed of noncannulated animals was sampled for LH
      secretion only as a control for the effects of surgical procedures. On each
      occasion, blood was collected every 10 min for 6 h. Between Day -1 and Day 39,
      LHRH pulse frequency was low and did not differ. In the same animals, this value
      became 2.5-fold higher between Day 39 and Day 46. Finally, on Day 74, LHRH pulse
      frequency was about 6-fold higher than on Day -1.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7626712
TI  - Sperm migration through the female genital tract of the New World monkey Cebus
      apella.
AB  - This study was designed to characterize sperm migration in the female genital
      tract of Cebus apella. Forty-eight cycles of eighteen females mated during the
      periovulatory period were studied. Eggs were searched for and spermatozoa were
      counted in segmental flushings of the genital tract performed in situ 1-7 h, 19
      31 h, or 45-56 h after coitus. Of 14 eggs recovered, 8 were fertilized, thus
      assuring a reasonable normality of prefertilization phenomena in both males and
      females. A downward gradient of several orders of magnitude in sperm numbers was
      recognized from cervix to ampulla, particularly over the first interval. The
      population in the cervix and uterus decreased progressively between the first and
      last interval. Spermatozoa were recovered from the ampulla as early as 1 h after
      mating. Different trends were observed in the isthmus and ampulla. From the first
      to the last interval, sperm numbers decreased in the ampulla, but not in the
      isthmus. The number of spermatozoa recovered from the ampulla of the ovulatory
      side 1-31 h postcoitum was higher in postovulatory than in preovulatory monkeys,
      while in the nonovulatory side, recovery was similar in the two conditions. This
      findings suggests that the passage of spermatozoa up to the site of fertilization
      is under local control and is synchronized with ovulation. The pattern of sperm
      migration that emerges from these data bears similarities to the pattern in
      nonprimate species as well as distinctive features. A unique feature in common
      with the pattern in human is the early establishment of a fairly abundant and
      persistent sperm population in the ampulla.

PMID- 7626713
TI  - Effect of persistent follicles on early embryonic losses in beef cows.
AB  - Low doses of progestogens in regimens for synchronization of estrus result in
      persistent follicles (PF) and reduced conception rates in cattle. The effects of
      PF on recovery of oocytes/embryos, fertilization, and embryonic development were
      examined in beef cows. To produce PF, cows received a used Controlled Internal
      Drug Releasing device on Days 4 through 13 after pretreatment estrus (Day 0) and
      two injections of 20 mg prostaglandin (PG) F2 alpha, i.m., 12 h apart on Day 6
      (PF; n = 20). Control cows received only PGF2 alpha on Day 6 so they would
      ovulate growing follicles (GF; n = 22). With this model, the largest (dominant)
      follicle from the first wave of follicular development was being ovulated in cows
      in each group. Cows were observed for estrus twice daily and were then mated to
      highly fertile bulls. Follicular development was monitored by ultrasonography on
      alternate days from Day 2 until estrus and then daily until apparent ovulation.
      Jugular blood samples were collected every other day from Day 2 through 6 days
      after mating at posttreatment estrus, when uteri were flushed nonsurgically. The
      ovulatory follicle, which was followed retrospectively and had been observed
      longer (14 +/- 1 vs. 8 +/- 1 days), was larger in PF (17.2 +/- 0.5 mm) than in GF
      (14.5 +/- 0.6 mm; p < 0.01). Mean estradiol-17 beta (E2) in jugular plasma during
      the 6 days before estrus was higher in PF than in GF (5.7 +/- 0.4 vs. 2.6 +/- 0.4
      pg/ml; p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7626714
TI  - Effects of bovine growth hormone (bGH) transgene expression or bGH treatment on
      reproductive functions in female mice.
AB  - Both physiological and excessive levels of growth hormone (GH) can affect
      reproductive functions. Overexpression of human (h) or bovine (b) GH in
      transgenic female mice was previously reported to be associated with reproductive
      deficits. The objectives of the present study were to determine the age of onset
      of puberty, the length of the estrous cycle, and the ovulation rate in transgenic
      and normal mice from a line expressing bGH with the phosphoenolpyruvate
      carboxykinase (PEPCK) promoter and characterized by very high levels of transgene
      expression. Transgenic females reached puberty, defined as the appearance of the
      vaginal introitus, earlier than their normal littermates, but at a higher body
      weight. Compared to normal animals, an increased number of transgenic females
      failed to mate during the 15-day period of observation, and pregnancy rates were
      reduced. However, ovulation rates, as estimated by counting CL and implantation
      sites on Day 7 postcoitum, were increased in transgenic females. Plasma bGH
      levels in transgenic females ranged from 700 to 2200 ng/ml and were negatively
      correlated with fertility. To assess the effect of bGH on the ovulation rate in
      non-transgenic mice, normal females were paired with normal males and injected
      for up to 3 days with either 0.75 mg bGH/day or 0.30 mg bGH/day (injected as a
      single dose or as 0.15 mg twice daily). Data from animals that mated after at
      least 2 days of bGH treatment were analyzed. The ovulation rate was increased in
      females treated with 0.75 mg bGH/day, as compared to controls, and in females
      injected with 0.15 mg bGH twice daily as compared to those given 0.3 mg bGH/day
      and to controls.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7626715
TI  - Relationship between the presence of endogenous nicks and sperm chromatin
      packaging in maturing and fertilizing mouse spermatozoa.
AB  - Mammalian spermiogenesis involves the replacement of histones by protamines,
      resulting in a highly compacted chromatin. Upon fertilization, the reverse
      process occurs. We have previously shown that the chromomycin A3 (CMA3)
      fluorochrome represents a useful tool for detecting protamine deficiency in
      spermatozoa. In this study we investigated CMA3 fluorochrome accessibility and
      the presence of endogenous nicks in maturing and fertilizing mouse sperm.
      Testicular sperm of stages 1-7 and 8-14 showed high positivity (> 96%) to CMA3,
      decreasing to 63% in stage 15-16 spermatids. In situ protamination of stage 15-16
      spermatids saw an inhibition of CMA3 accessibility. Only 8% of the mature
      spermatozoa in the efferent ducts were CMA3-positive; this value decreased to 0%
      in the caput epididymidis. At fertilization, CMA, fluorescence reappears in
      decondensing sperm. Fluorescein isothiocyanate (FITC) fluorescence, identifying
      endogenous nicks, was evident in 6% of stage 1-7 spermatids, increased to 22% in
      stage 8-14 spermatids, and disappeared in stage 15-16 spermatids. During
      fertilization, endogenous nicks were not observed in decondensing sperm. We
      propose that 1) the presence of nicks in mouse testicular spermatids suggests
      that DNA cutting and ligating occurs prior to completion of protamination and 2)
      the absence of nicks during fertilization indicates that decondensation is not
      simply the reversal of the initial chromatin packaging process.

PMID- 7626716
TI  - Regulation of luteinizing hormone-releasing hormone (LHRH) secretion by melatonin
      in the ewe. II. Changes in N-methyl-D,L-aspartic acid-induced LHRH release during
      the stimulation of luteinizing hormone secretion by melatonin.
AB  - Injection of N-methyl-D,L-aspartic acid (NMDA), a glutamatergic agonist, cause an
      acute release of LH. The amount of LH released is modulated by photoperiod in
      sheep; it is larger in animals in which reproductive activity has been inhibited
      by long days than in those photostimulated by short days. The purpose of the
      present experiment was to determine whether this effect of photoperiod on LH
      response to NMDA is mediated by melatonin and whether it reflects a change in the
      amount of LHRH released in response to NMDA. Twenty-one ovariectomized ewes,
      bearing an s.c. implant of estradiol and kept in long days (16L:8D), received
      s.c. implants of melatonin on Day 0. The effect of a single injection of NMDA (5
      mg/kg i.v.) on LHRH and simultaneous LH secretion was studied at three different
      periods of the stimulation of LH secretion by the melatonin treatment: first,
      during inhibition of LH secretion by long days (on Day -1, n = 6); secondly,
      during the onset of the LH increase (on Day 39, n = 9); and thirdly, during
      maximum LH secretion (on Day 74, n = 6). The stimulation of LHRH secretion by
      administration of NMDA was characterized by a large and long increase in LHRH
      concentration on Day -1 and Day 39. There was no significant difference between
      these two periods in terms of duration and amplitude of the LHRH release. On Day
      74, the stimulation was much shorter than on Day -1 and Day 39 and was followed
      by a phase of decreased pulsatility of LHRH secretion.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7626717
TI  - Infertility in transgenic mice overexpressing the bovine growth hormone gene:
      luteal failure secondary to prolactin deficiency.
AB  - Overexpression of growth hormone (GH) in transgenic mice is associated with
      various degrees of impairment of female reproductive functions. Transgenic
      PEPCK.bGH mice express high GH levels, and only around 20% of the females will
      carry gestation to Day 7. The objective of the present study was to investigate
      luteal function in PEPCK.bGH mice during early pregnancy, when CL are fully
      dependent on the pituitary. Plasma progesterone levels measured on Days 2 or 7
      postcoitum (p.c.) were lower in transgenic than in normal females. In transgenic
      females with a previous history of infertility, daily injections of 1 mg
      progesterone starting on Day 2 p.c. significantly increased the proportion of
      animals pregnant on Day 7. When ovaries from transgenic mice were transplanted
      into ovariectomized normal littermates, the recipients exhibited normal vaginal
      cycles and responded to mating by vaginal cytology changes consistent with
      pseudopregnancy. In contrast, ovariectomized transgenic females bearing
      transplants of ovaries from normal mice had slightly prolonged estrous cycles and
      failed to become pseudopregnant after mating. Plasma progesterone levels on Days
      2 and 7 p.c. in normal females with transgenic ovaries were not different from
      plasma progesterone levels measured in normal females into which normal ovaries
      had been transplanted. Twice-daily injections of 100 micrograms of prolactin
      (PRL) in saline or in polyvinylpyrrolidone starting on the evening of Day 2 p.c.
      were able to rescue luteal function. The proportion of PRL-injected transgenic
      animals that were pregnant on Day 7 was significantly higher than that of saline
      injected transgenic controls and resembled the pregnancy rate of normal
      animals.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7626718
TI  - Immunogenicity enhancement of recombinant rabbit 55-kilodalton zona pellucida
      protein expressed using the baculovirus expression system.
AB  - In the present study we have used a molecular approach to evaluate the
      immunogenicity and antigenicity of glycosylated and non-glycosylated recombinant
      rabbit 55-kDa zona pellucida (ZP) protein. The 55-kDa cDNA was expressed in
      insect (Sf9) cells through use of a baculovirus expression system to obtain
      nonfusion glycosylated recombinant ZP protein (BV-55). SDS-PAGE and immunoblot
      analysis demonstrated that the recombinant protein is expressed as two forms
      having relative molecular masses of 70 kDa and 80 kDa. Because cells treated with
      tunicamycin produce predominantly the 70-kDa form, this heterogeneity is presumed
      to be due to differential glycosylation. Further studies using lectin blot and
      immunoblot analyses showed that the BV-55 protein has both N-linked and O-linked
      oligosaccharides. However, this glycosylation is distinct from that of the native
      55-kDa ZP protein, since it was not recognized by a monoclonal antibody
      associated with lactosaminoglycan-type carbohydrate epitopes in native ZP
      proteins. Immunogenicity studies demonstrated that antibodies against the BV-55
      protein are developed by female rabbits and guinea pigs and that these antibodies
      recognize epitopes associated with native, enzyme-deglycosylated as well as
      nonglycosylated recombinant forms of the rabbit 55-kDa ZP protein. In contrast,
      recombinant protein expressed in bacteria did not elicit antibodies in either
      rabbits or guinea pigs. These results demonstrate that expression of the 55-kDa
      recombinant protein in the baculovirus expression system enhances its
      immunogenicity.

PMID- 7626719
TI  - Infertility in transgenic mice overexpressing the bovine growth hormone gene:
      disruption of the neuroendocrine control of prolactin secretion during pregnancy.
AB  - Transgenic female mice overexpressing the bovine growth hormone (bGH) gene with
      the phosphoenolpyruvate carboxykinase (PEPCK) promoter exhibit severe
      reproductive deficits. Although these animals ovulate and conceive normally,
      pregnancy is arrested due to luteal failure, leading to the loss of embryos
      during early gestation. The results of replacement therapy suggested that luteal
      failure was secondary to prolactin (PRL) deficiency. The objective of this study
      was to examine the neuroendocrine control of PRL secretion during early pregnancy
      in PEPCKbGH-1 transgenic mice. Normal and transgenic littermates were killed by
      decapitation on Day 7 postcoitum (p.c.) at 1500, 1800, or 2100 h, i.e., the
      period including the expected diurnal PRL surge in pregnant mice. In normal
      females, plasma PRL levels were significantly elevated at 1800 h when compared to
      the levels measured at 1500 or 2100 h, but no temporal variation in PRL levels
      was found in transgenic mice. In normal females, the content of dopamine in the
      median eminence was reduced at 1800 h, i.e., at the time of the PRL surge. In
      contrast, no temporal changes were detected in the median eminence dopamine
      content in transgenic mice. Twice-daily injections of domperidone, a dopamine
      receptor blocker, increased the incidence of pregnancy in transgenic females.
      After treatment with aromatic amino acid decarboxylase inhibitor NSD-1015 on Day
      7 p.c., plasma levels of PRL were similarly elevated in transgenic and normal
      females. However, the accumulation of 5-hydroxytryptophan (5-HTP) in the medial
      basal hypothalamus after this treatment was significantly smaller in transgenic
      than in normal females.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7626720
TI  - Gonadotropin-releasing hormone analog-induced patterns of luteinizing hormone
      secretion in female Wapiti (Cervus elaphus nelsoni) during the breeding season,
      anestrus, and pregnancy.
AB  - We conducted two studies to determine the pattern of GnRH analog-induced LH
      secretion in adult female wapiti during the breeding season, anestrus, and
      pregnancy. In the first study, we measured LH secretion during the breeding
      season and anestrus in five females challenged with each of five doses of GnRH
      analog (0.3, 1, 3, 10, and 30 micrograms/50 kg BW). In the second study, LH
      response was determined in six pregnant females treated with six doses of GnRH
      analog (0.5, 1, 2, 4, 8, and 16 micrograms/50 kg BW). Animals were fitted
      nonsurgically with indwelling jugular catheters, and blood samples were collected
      at 0, 30, 60, 90, 120, 180, 240, 300, 360, 420, and 480 min postinjection. Mean
      maximum serum concentrations of LH were not different (p = 0.45) between females
      treated during the breeding season (mean = 29.1 +/- 1.9 [SE] ng/ml) and anestrus
      (mean = 32.4 +/- 4.3 [SE] ng/ml); however, anestrous females required 3.3 times
      more GnRH analog (3 vs. 10 micrograms/50 kg BW) to produce the same response.
      Maximal inducible LH concentrations were lowest (mean = 7.7 +/- 2.5 [SE] ng/ml)
      for pregnant wapiti, and the magnitude of the response decreased exponentially
      (r2 = 0.98, p = 0.002, SEb = 0.65) during gestation. Although the magnitude of
      the response declined over time, maximal release consistently occurred at the
      same dose (2 micrograms/50 kg BW) (treatment x trial interaction, p = 0.53). We
      conclude from these studies that the amount of LH released in response to a given
      dose of GnRH analog depends on reproductive status.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7626721
TI  - Regulation of brain androgen receptor immunoreactivity by androgen in prepubertal
      male ferrets.
AB  - During pubertal maturation, there is an increase in the number of androgen
      receptor-immunoreactive (AR-IR) cells in the preoptic area (POA), arcuate nucleus
      (ARC), medial amygdala (mAMY), and ventromedial hypothalamic nucleus (VMH) of the
      male ferret brain. In contrast, the number of AR-IR cells in the bed nucleus of
      the stria terminalis (BNST) or lateral septum (ISEP) does not change with
      pubertal development. This experiment tested the hypothesis that the pubertal
      increase in AR-IR cells in certain brain regions is the result of the pubertal
      increase in circulating androgens. Prepubertal male ferrets were left intact or
      were castrated and treated daily (10 days) with s.c. injections of either oil,
      testosterone (T; 5 mg/kg), dihydrotestosterone (DHT; 5 mg/kg), or estradiol (E;
      10 micrograms/kg). Brains were processed for AR immunocytochemistry, and the
      number of immunopositive cells was quantified in POA, ARC, mAMY, VMH, BNST, and
      ISEP. Overall, castration reduced the number of AR-IR cells below that seen in
      intact animals, and E administration did not restore AR-IR cell number. Treatment
      of castrates with androgens restored numbers of AR-IR cells to those of intact
      animals in the BNST, ISEP, and VMH. However, AR-IR cell numbers were
      significantly greater in androgen-treated castrates than in intact animals in
      POA, mAMY, and ARC. These data show that AR-IR cells in prepubertal male ferrets
      are sensitive to circulating levels of androgens, supporting the hypothesis that
      the pubertal rise in T is responsible for the pubertal increase in the number of
      AR-IR cells in the POA, mAMY, and ARC.

PMID- 7626722
TI  - Activity of platelet-activating factor acetylhydrolase in the mouse uterus during
      the estrous cycle, throughout the preimplantation phase of pregnancy, and
      throughout the luteal phase of pseudopregnancy.
AB  - Platelet-activating factor (PAF) is a potent autacoid produced by the embryo and
      the endometrium during early pregnancy. Its actions in vivo are dependent upon
      its half-life, which in turn is largely governed by its metabolism.
      PAF:acetylhydrolase is a major metabolic enzyme for PAF and is widespread in body
      tissues and fluids. This study was an examination of the activity of this enzyme
      in the uterus (uterine luminal fluids and endometrial scrapings) of mice in the
      periovulatory period, throughout the preimplantation phase of pregnancy, and
      throughout the luteal phase of pseudopregnancy. PAF:acetylhydrolase activity was
      found in uterine washings and endometrial tissue; it was dependent upon
      incubation time and protein concentration and was destroyed by boiling. The
      activity was not affected by cations (Mg2+ and Ca2+) and was not inhibited by
      bromophenacyl bromide, a phospholipase A2 inhibitor. The specific and total
      activity changed dramatically throughout the reproductive cycle. Total tissue
      activity did not change significantly during the follicular phase. On the day
      after ovulation, tissue activity was lower in naturally mated mice and was
      maintained at this level until Day 4; there was no difference in this value
      between pregnant and pseudopregnant animals. On days 5 and 6 of pseudopregnancy
      the total tissue activity increased, reaching a peak on Day 6 of 4609 pmol
      acetate released.min-1, approximately 780% higher than the value obtained on Day
      4. Activity then decreased so that by Day 8 it was not different from
      preovulatory levels. For uterine luminal fluids, total activity significantly
      decreased during the follicular phase. This continued throughout the
      preimplatation phase with minimum activity being reached on Days 3 and 4 (7.68
      pmol acetate.min-1 on Day 4 pseudopregnancy).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7626723
TI  - Dual actions of phorbol ester on cytochrome P450 cholesterol side-chain cleavage
      messenger ribonucleic acid accumulation in porcine granulosa cells.
AB  - In earlier studies in cultures of porcine granulosa cells prepared from small
      antral follicles, steroidogenesis-related loci were inhibited by treatment for 48
      h with 12-O-tetradecanoyl-phorbol-13-acetate (TPA), a potent activator of protein
      kinase C (PKC). In the present investigation, cells were incubated in serum-free
      medium for 48 h, with various agents present during the last 2-24 h. With TPA at
      30 ng/ml, the FSH-stimulated cAMP accumulation was markedly enhanced at all time
      points. FSH increased the concentration of cytochrome P450 cholesterol side-chain
      cleavage (P450scc) mRNA throughout the 24-h incubation. At 4 and 8 h, TPA
      increased the accumulation of P450scc mRNA, having an additive effect with FSH.
      However, at 24 h, TPA markedly suppressed the FSH-induced increased in P450scc
      mRNA. Pretreatment of cells with FSH did not shorten the time required for TPA to
      become inhibitory. The stimulatory effect of 8-bromo-cAMP on P450scc mRNA also
      was augmented by TPA at 4 h, but significant inhibition was not observed at 24 h.
      The concentration of glyceraldehyde-3-phosphate dehydrogenase mRNA, intended to
      be used for correction of gel loading, was stably increased by both cAMP and TPA.
      These effects of TPA suggest multiple actions of PKC(s) on the regulation of
      P450scc expression and other endpoints in ovarian granulosa cells.

PMID- 7626724
TI  - Sperm quality and ascorbic acid concentration in rainbow trout semen are affected
      by dietary vitamin C: an across-season study.
AB  - High concentrations of ascorbic acid occur in scurvy-prone, teleost fish plasma.
      We quantified seasonal relationships between 1) dietary level of vitamin C and
      level of seminal plasma ascorbic acid, and 2) seminal plasma ascorbic acid
      concentration and sperm quality, in rainbow trout (Oncorhynchus mykiss). We
      maintained six groups of 2-yr-old rainbow trout on diets supplemented with 0, 30,
      110, 220, 440, and 870 ppm ascorbyl monophosphate beginning in May 1992. Sperm
      were produced during the end of October 1992 through April 1993; we collected
      milt 13 times from 3-8 fish per treatment. We quantified ascorbic acid
      concentration in seminal plasma, and sperm concentration, motility, and weight.
      Seminal plasma ascorbic acid concentrations were affected directly by the
      ascorbyl monophosphate level in the diet. Seminal plasma ascorbic acid
      concentrations also were affected by season. Ascorbic acid deficiency did not
      influence semen quality (sperm concentration and motility) at the beginning of
      the spawning season. However, sperm concentration and motility in a group fed an
      ascorbic acid-free diet declined during the period of study. Ascorbic acid
      deficiency reduced both sperm concentration and motility, and thus fertility, of
      rainbow trout. These results indicate that vitamin C is important for male fish
      reproduction; the dietary requirement for seminal plasma ascorbic acid saturation
      exceeds that for optimum growth.

PMID- 7626726
TI  - Testicular steroidogenesis in the Cebus monkey throughout postnatal development.
AB  - There is scant information on testicular steroidogenesis during postnatal
      development in monkeys, particularly in New World species. Our purpose was to
      study the in vitro steroidogenic capacity of the Cebus monkey testis from birth
      to advanced puberty. Fresh testicular tissue was incubated in Medium 199 with or
      without hCG (10 IU/ml); and levels of pregnenolone (P5), dehydroepiandrosterone
      (DHA), progesterone (P4), androstenedione (A), testosterone (T),
      dihydrotestosterone (DHT), and 3 alpha-androstanediol (3 alpha-DIOL) were
      measured in tissue and incubation media by RIA. To determine the predominant
      steroidogenic pathway, the ratio between the concentrations of the 5-ene and the
      4-ene T precursors was determined, and the relative conversion of 3H-P5 and 14C
      P4 to T was calculated. The number of Leydig cells per testis was determined in
      all experimental groups. The testes of the Cebus monkeys could produce T in vitro
      without the addition of gonadotropins at all ages. T and the 5-ene precursors (P5
      and DHA) were the main steroids found within testicular tissue throughout
      postnatal development. T content per Leydig cell increased continuously with age,
      but testicular T concentration reached maximal levels at early puberty and did
      not change thereafter. The ratios between 5-ene and 4-ene T precursors ranged
      between 2.8 and 13.2, which suggested a predominance of the delta-5 pathway. This
      was confirmed by the finding that 3H-P5 was more efficiently converted to T than
      was 14C-P4. The T production relative to that of its d-ene precursors
      progressively increased to reach maximal values in late puberty.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7626725
TI  - Effects of prenatal and postnatal photoperiods and of the pineal gland on early
      testicular development in the marsh rice rat (Oryzomys palustris).
AB  - Prepubertal male rice rats are responsive reproductively to photoperiod early in
      postnatal development. Testicular growth was inhibited in animals gestated and
      reared to 28 days of age on photoperiods ranging from 8 to 13 h of light per day,
      and stimulated in animals reared on 14 h or more of light per day, suggesting a
      critical photoperiod between 13 and 14 h for testicular growth. In addition,
      postnatal photoperiod markedly affected testicular development in animals exposed
      to various prenatal and postnatal photoperiods. Postnatal exposure to constant
      light unmasked effects of the prenatal photoperiod on testicular development.
      Exposure of rice rats to short or long photoperiods during the period of
      lactation (Days 1-14 of life) affected testicular maturation. In addition,
      alteration of the photoperiod experienced after Day 14 of life (post-lactational)
      markedly affected testicular development and was the primary factor determining
      whether maturation would occur. Finally, pinealectomy had little to no effect on
      the magnitude of testicular development in animals maintained on the presurgical
      photoperiod, but did prevent animals from demonstrating the appropriate
      testicular response to a new photoperiod after surgery. These data suggest that
      early testicular development in rice rats is affected by the prenatal and
      postnatal photoperiod and that the pineal gland is involved in the transduction
      of this environmental information.

PMID- 7626727
TI  - Plant storage proteins.

PMID- 7626728
TI  - [Notes on the relationships of support and collaboration between primary care
      teams and mental health teams].

PMID- 7626729
TI  - [Myopathies can be the cause of a moderate rise in transaminases].

PMID- 7626730
TI  - [Gynaecomastia produced by nifedipine].

PMID- 7626731
TI  - [The editorial process in the journal Atencion Primaria].

PMID- 7626732
TI  - [Antithrombotic treatment in auricular fibrillation].

PMID- 7626733
TI  - [Conjugated vaccines against Haemophilus influenzae type b].

PMID- 7626734
TI  - [Macroangiopathy in type II diabetes. The Raval South study].
AB  - OBJECTIVE: To study the prevalence of clinical forms of diabetic macroangiopathy
      (DM) and its risk factors. DESIGN: A descriptive crossover study. SETTING: An
      elderly and socio-economically very depressed population in Raval Sud Health
      District (HD), Barcelona. PATIENTS AND OTHER PARTICIPANTS: Random sampling of
      type II diabetes patients (n = 387) registered in the HD (6.6% prevalence).
      MEASUREMENTS AND MAIN RESULTS: Each patient was examined for the presence of
      diagnostic criteria of peripheric, cerebral or coronary vasculopathy (VP); as
      well as for the possible risk factors (age, gender, years of the DM's evolution,
      tobacco, hypertension, obesity, glycosilated haemoglobin and dyslipemia).
      Prevalences obtained were: peripheric VP = 24.5%, cerebral VP = 9.5%, coronary VP
      = 18.1%. 30.5% of the diabetics had some form of macroangiopathy. The main risk
      factors for all the clinical forms (p < 0.001) were age and the length of
      evolution of DM, tobacco mainly for peripheric VP (p < 0.001), systolic
      Hypertension for cerebral VP (p = 0.03) and Hypertriglyceridaemia for peripheric
      VP (p < 0.01). CONCLUSIONS: Macroangiopathy affects a high percentage (30.5%) of
      type 2 diabetics. The principal risk factors are those associated with tobacco,
      hypertension and hypertriglyceridaemia, all of which we can affect and control.

PMID- 7626735
TI  - [Study of the demand for laboratory tests in primary care].
AB  - OBJECTIVE: To study the demand for laboratory test from a sample of Primary Care
      doctors. DESIGN: A crossover observational study. SETTING: Primary care medical
      clinics in Spain and Andorra. PARTICIPANTS: Volunteer doctor with primary care
      practices. INTERVENTION: The study was based on: a) a questionnaire to the
      doctors taking part, on their clinical consultations, b) recording of the age and
      gender of patients seen during four consecutive weeks, and c) the logging of the
      laboratory tests requested during these four weeks. MAIN RESULTS: 82 doctors took
      part. They had 37,383 clinical consultations, asking for 1,965 analytical studies
      with 7,248 tests; i.e., they generated 5.25 requests for analysis per hundred
      consultations. The doctors who requested most analyses had less consultations/day
      and less consultations/inhabitants/year. When the distance to the laboratory
      increased, the analyses per consultation lessened and the analyses per inhabitant
      went up. The most common reason for requesting analysis was the follow-up of an
      already-known pathology. CONCLUSIONS: A request for analysis is made in 5.25% of
      primary care consultations. The most common reason is to follow up an already
      known pathology.

PMID- 7626736
TI  - [Quality improvement in primary care: experience of four years of a quality
      improvement program].
AB  - OBJECTIVE: To assess the effectiveness of the quality improvement programme (QIP)
      at the centre. DESIGN: A retrospective analysis of the "improvable situations"
      detected between 1988 and 1992, their causes and the methods used for their
      detection. The present status of the improvable situations (solutions) was then
      studied. SETTINGS: La Mina Primary Care Centre. PATIENTS AND OTHER PARTICIPANTS:
      The improvable situations detected from the start of the QIP in March 1989 until
      December 1992. MEASUREMENTS AND MAIN RESULTS: 172 situations were identified,
      corresponding to 83 different problems, situations or opportunities of
      improvement. The method which identified the most different and solvable
      situations (64.5%) was the use of the improvable situation report sheet (problem
      report) by the professionals at the centre. The component of quality most often
      affected was accessibility; and the least, satisfaction. The effectiveness
      component had the highest percentage of situations solved (64.3%) and external
      problems, the lowest (30%). 62 out of the 180 causes (34.4%) for the 73
      improvable situations, which did not affect external aspects of care, were
      solved. The commonest and most solvable causes were due to lack of internal
      organisation (64%). 51.8% of the 83 situations detected were solved. There was
      73.2% effectiveness of the QIP, measured as a percentage of solved situations,
      not including those situations with external causes or depending on the user.
      CONCLUSIONS: The most useful method of detecting solvable solutions is the use of
      the improvable situations report sheet by the professional.

PMID- 7626737
TI  - [Study of short-term unfitness for work because of common illness among primary
      care management employees].
AB  - OBJECTIVES: To find the level of absenteeism among workers in the primary care
      management of Murcia, along with their distribution by professional category,
      health area, age and gender; and (2) find the causes of absenteeism and the
      relationship between these causes and the number of days lost. DESIGN: A
      descriptive, retrospective, population-based study. SETTING: Primary care
      management in Murcia. POPULATION: The management staff in Murcia consisted of
      1,225 employees, who overall had 610 short-term periods of unfitness for work
      (SUW) due to common illness and accidents not at work, between October 1st, 1992
      and October 1st, 1993. The variables studied were: age, gender, professional
      category, area where they worked, reason for and length of SUW and type of care.
      MAIN RESULTS: Index of absenteeism (IA) = 0.50, index of Seriousness (IS) =
      40.75, Index of Incapacity (IL) = 18.12 and overall rate (OR) = 4.96. We found a
      large amount of SUW "without diagnosis": 104 cases (17.04%), which was the second
      most frequent cause behind respiratory complaints (23.77%). The IS were high in
      pathologies of the circulatory system, mental illness and neoplasias.
      CONCLUSIONS: The length of SUW (IS) is not influenced by any of the variables
      studied, excepting the specific cause of the SUW. II and IA are affected by the
      model of care (greater in the traditional type, p < 0.05), the health area where
      they work (p < 0.001) and professional category (p < 0.001). The filling out the
      sickness note must be improved in order to lessen the number of SUWs "without
      diagnosis".

PMID- 7626738
TI  - [Emergency care in the city of Salamanca].
AB  - OBJECTIVES: To find, through a study of the Casualty Department (CD) of the
      University Hospital of Salamanca, the numbers of patients attending on their own
      initiative and those sent with a referral note by Primary Care (PC) doctors; and
      to analyse the quality of both the PC referral documents and the CD reports.
      DESIGN: A descriptive, retrospective study of Clinical Records, applying criteria
      for evaluating the quality of PC documents and CD reports. SETTING: Casualty
      Department of the University Hospital of Salamanca, consisting of two hospitals.
      PARTICIPANTS: Overall, 2,299 Clinical Records (patients) were used: 941 and 1,359
      requests for care, respectively for the two hospitals, in one week. RESULTS:
      There was a high degree of direct use of the CD. The quality analysis revealed a
      low level of compliance in the referral documents written by the PC doctors and,
      on the contrary, high compliance in reports by the CD doctors. CONCLUSIONS:
      Social-health factors may have an impact on the high use of the CD on the users'
      own initiative. There is no adequate understanding or coordination between the
      different care levels, as is demonstrated by the low quality of PC doctors'
      referral documents and the high level of compliance in the reports written by CD
      doctors.

PMID- 7626739
TI  - [Reflex sympathetic dystrophy: vision and revision of primary care].

PMID- 7626740
TI  - Effects of cholesterol on transmembrane water diffusion in human erythrocytes
      measured using pulsed field gradient NMR.
AB  - The effect of cholesterol on the diffusional permeability of water in suspensions
      of human erythrocytes was studied by means of pulsed field gradient NMR, which
      unlike the relaxation NMR method avoids the use of Mn2+ ions. The analysis allows
      the internal and external diffusion coefficients, as well as the lifetime
      characterizing the rate of exchange between the two regions, to be extracted from
      the data. The cholesterol content of the erythrocyte membranes was altered by
      incubating the cells with sonicated dispersions of cholesterol/dipalmitoyl
      phosphatidylcholine at 310 K. It was shown that decreasing the molar ratio of
      cholesterol to phospholipid (C/P ratio) of the membrane, from a mean value of
      0.92 for normal cells (controls) to a value of 0.46, had little effect on the
      intracellular mean residence lifetime and the diffusional permeability. Enriching
      the cholesterol content of the membrane, however, had a marked effect on the
      exchange lifetime and the diffusional permeability. At a C/P ratio of
      approximately 1.5 the rate of transport was reduced approximately 3.5-fold. A
      further increase of the cholesterol content, to a C/P ratio of approximately 1.9,
      resulted in an enhancement of the rate of transport back to a normal (control)
      value, which was characterized by a lifetime of 8-9 ms. The combined inhibition
      of the water permeability by cholesterol and pCMBS for cells with C/P ratios of
      1.44 and 1.54, and by pCMBS alone for cells with a control C/P ratio resulted in
      the same value for Pd within experimental error.

PMID- 7626741
TI  - Possible prediction of taste quality using a liquid membrane.
AB  - Oscillations of electric potential across a liquid membrane consisting of picric
      acid in nitrobenzene between two aqueous layers were studied. When fully
      described the oscillations were found to be characteristic of the structural
      class of a tastant present in the RHS of the liquid membrane. Smaller variations
      were observed in the pattern of oscillations and were apparently related to
      variations in the taste qualities within that class.

PMID- 7626742
TI  - Structural features of isolated M2 helices of nicotinic receptors. Simulated
      annealing via molecular dynamics studies.
AB  - The nicotinic acetylcholine receptor is an integral membrane protein and a ligand
      gated cation channel. It has stoichiometry alpha 2 beta gamma delta, the subunits
      arranged symmetrically around an approximate five-fold axis. Five M2 helices, one
      from each subunit, form a parallel helix bundle surrounding a central pore.
      Simulated annealing via restrained molecular dynamics (SA/MD) has been employed
      to generate ensembles of isolated M2 transmembrane helices. Four ensembles of two
      different M2 helix sequences, M2 delta and M2 gamma, have been generated by
      SA/MD. The ensembles differed in their treatment of electrostatic interactions.
      Analysis of the simulated structures showed that intra-helical H-bonds were more
      strongly conserved in the C-terminal (and more hydrophobic) segment of M2
      helices. Conformations of polar sidechains have been analyzed, placing particular
      emphasis on EK (and QK) pairs at the N-termini of M2 delta (and M2 gamma)
      helices. Conformations of EK sidechain pairs were obtained for the high
      resolution structures in the protein database in order to guide our analysis of
      simulated structures. Serine and threonine sidechain conformations in the M2
      models also have been determined. Implications of studies of isolated M2 helices
      for models of the intact pore region of the nicotinic receptor are discussed.

PMID- 7626743
TI  - Thermodynamics of the thermal unfolding of eglin c in the presence and absence of
      guanidinium chloride.
AB  - The thermal unfolding of eglin c, a small proteinase inhibitor of molecular
      weight 8.1 kDa, is studied by means of high sensitivity scanning calorimetry over
      a wide pH range in dilute buffer solutions, and in the presence of varying
      concentrations of guanidinium chloride at pH 7.00 and 10.55. The temperature of
      half-completion of the unfolding transition, t1/2, in dilute buffer varies from
      41 degrees C at pH 1.1 to 86 degrees C at pH 7.0 to 10.55, with corresponding
      enthalpy changes of approximately 40 kcal mol-1 and 71 kcal mol-1. This latter
      enthalpy change, amounting to 8.7 cal g-1, is unusually large for a protein,
      especially for one of unusually small molecular weight. Addition of 3.3 M
      guanidinium chloride at pH 10.55 lowered t1/2 from 86 degrees C to 40 degrees C
      and decreased the enthalpy change from approximately 71 kcal mol-1 to 25 kcal mol
      1.

PMID- 7626745
TI  - Difference in surface properties between Escherichia coli and Staphylococcus
      aureus as revealed by electrophoretic mobility measurements.
AB  - Electrophoretic mobilities of Escherichia coli and Staphylococcus aureus were
      measured in media of different pH values and ionic strengths at 310 K and the
      results were analyzed via a new mobility formula which was derived on the
      assumptions of uniform charge distribution in the cell surface layer of finite
      thickness and ion-penetrability in the layer. E. coli was shown to have a more
      negatively charged and less soft surface than that of S. aureus. It is suggested
      that electrophoretic mobility measurements can be used to detect the difference
      in surface structure between gram-positive and gram-negative bacteria.

PMID- 7626744
TI  - Influence of dynamic fluctuations on DNA curvature.
AB  - The effect of dynamic fluctuations on physical manifestations of DNA curvature
      such as electrophoretic retardation, circularization of DNA tracts and
      nucleosomes positioning is examined. It is shown that in all cases the main
      features of the processes can be satisfactorily explained by a static curvature
      model, which appears to be a good representation of time and ensemble averaged
      superstructures of DNA chains. The dynamic fluctuations around the average
      curvature appear to influence only the kinetics of these processes. In the case
      of polyacrylamide gel electrophoretic retardation it is demonstrated that the
      approximation of the static model holds on the assumption that dynamic
      fluctuations are independent from intrinsic curvature. The actual validity of the
      static model we proposed several years ago is satisfactorily demonstrated by the
      explanation and prediction of different experiments, such as cyclic permutation
      gel electrophoresis, differential DNAase I cleavage of cyclic versus linear DNA
      tracts and nucleosome positioning.

PMID- 7626746
TI  - Separation of overlapping spectra from evolving systems using factor analysis. 4.
      Fluorescence spectra of hematoporphyrin IX.
AB  - Fluorescence spectra of hematoporphyrin IX (Hp) in water and in aqueous SDS
      solutions are obtained in the pH range 0.1 to 13 to determine the ionisation
      state of the molecule as a function of pH. In water, the spectra are complicated
      by aggregation which is quite severe near pH 4. In aqueous SDS, the aggregation
      is much less violent. Factor analysis (FA) is used to identify five species in
      the fluorescence spectra in each series of solutions. The distribution curve of
      these species as a function of pH is also obtained. By comparing the spectra and
      the distribution curve of Hp with those of HPPEEA, an ethanolamide derivative of
      Hp that does not contain the carboxylic groups (Part 3), the species are
      identified. For Hp in water we have obtained the following species: the dication
      in two allotropic forms in the pH range 0 to 5; the monocation (with the charge
      on an imino nitrogen) in the pH range 2 to 7; and the free base in the pH range
      3.5 to 13. The monocation observed by the second derivative technique revealed
      three subspecies. For Hp in aqueous SDS we have obtained the following species;
      one dication in the pH range 0 to near 4; one monocation (with the charge on an
      imino nitrogen) in the pH range 0.5 to 9; three free bases (with no charge on the
      imino nitrogen) in the pH range 4 to 13. Of the latter, one species is the
      neutral molecule, another is a dianion (with the charges on the carboxylic side
      chains), and the third one appearing at pH higher than 10 is an allotropic form
      of the dianion.

PMID- 7626747
TI  - [Interventional radiology and the public health structures law].

PMID- 7626748
TI  - [Spiral CT of the pancreas. A clinical comparison with conventional CT and
      dynamic CT].
AB  - PURPOSE: Spiral CT is compared with the dynamic CT and the conventional CT with
      regard to the enhancement of the pancreas and peripancreatic vessels and the
      visualisation of anatomic details. METHODS: In 15 patients spiral CT of the
      pancreatic region was performed in the arterial phase followed by spiral CT of
      the upper abdomen in the arterial-venous phase. In 30 patients dynamic CT (n =
      15) and spiral CT (n = 15) of the pancreatic region was performed in the arterial
      phase followed by conventional CT of the upper abdomen. RESULTS: Compared with
      dynamic CT, spiral CT of the pancreatic region in the arterial phase (flow 4
      ml/s, delay 15-18 s) leads to a stronger contrast of the peripancreatic vessels
      (p < 0.001) and the pancreas (108 vs. 86 HU) (p < 0.05). In the following spiral
      CT of the upper abdomen (flow 1 ml/s, delay 70 s), a high enhancement of both
      arteries and veins could be achieved. Intrapancreatic structures and
      peripancreatic vessels were better seen in the spiral CT than in the conventional
      CT (p < 0.05) and p < 0.005, respectively). CONCLUSION: The combination of spiral
      CT of the pancreatic region in the arterial perfusion phase and spiral CT of the
      upper abdomen in the arterial-venous phase enables an optimal enhancement of the
      pancreas and the abdominal vessels and a reliable visualisation of anatomic
      details.

PMID- 7626749
TI  - [Cine-MRT in the functional and morphological diagnosis of the heart after a
      myocardial infarct/ A comparison with angiocardiography, 2-dimensional
      echocardiography, intracardiac scintigraphy and enzymatic infarct size
      estimation].
AB  - PURPOSE: The aim of the study was to test the reliability of cine magnetic
      resonance imaging (cine-MRI) on the infarction heart with its altered geometry.
      MATERIAL AND METHODS: 61 patients (17 women, 44 men, 36-83 years, 32 with
      anterior, 29 with posterior wall infarction) received Cine-MRI in the true long
      and short axis of the heart and two-dimensional echocardiography one and 4 weeks
      post infarction. Two-level angiocardiography (ACG) and radionuclide
      ventriculography (RNV) were performed 4 weeks p.i. The size of myocardial
      infarction was determined enzymatically with the CK integral method. Left
      ventricular volume indices (EDVI, ESVI, SVI), ejection fraction (EF) and
      infarction weight (IW) were compared. RESULTS: Excellent correlations existed
      between cine-MRI in the long and short axis for the volume indices and EF.
      Between cine-MRI in the short axis and ACG all correlations were excellent as
      well. They were significantly less satisfactory between cine-MRI and 2DE due to
      the inhomogeneity of echo quality. Cine-MRI and RNV produced similar EF results
      (r = 0.884), and a comparison of IW in cine-MRI and CK integral method also
      showed a good correspondence (r = 0.967). CONCLUSION: Cine-MRI is a reliable
      method for the morphological and functional examination of post-myocardial
      infarction.

PMID- 7626750
TI  - [The value of MR tomography in traumatic patella dislocations].
AB  - PURPOSE: To describe the MR imaging findings in patients with lateral patellar
      dislocation. MATERIAL AND METHODS: The MRIs of 31 patients with patellar
      dislocation were evaluated retrospectively. Arthroscopic surgery was performed in
      23 cases. RESULTS: Hemarthrosis was found in 30/31, contusions of the lateral
      femoral condyle in 30/31 and of the medial patellar facet in 26/31 cases. Injury
      of the medial patellar retinaculum was seen in 28/31 cases. Osteochondral
      fractures were found in 18 patients; compared to arthroscopy there were one false
      positive and 5 false-negative findings concerning loose cartilage bodies. In 7
      cases, patellar dislocation was not suspected before MR imaging. CONCLUSION:
      Hemarthrosis, lateral femoral and medial patellar contusion, and retinacular
      disruption are typical findings after lateral patellar dislocation. A careful
      search for free osteochondral fragments is mandatory as it influences the
      indication and performance of arthroscopic surgery.

PMID- 7626752
TI  - [Radiographically demonstrable spinal changes in asymptomatic young men].
AB  - PURPOSE: To find reliable data of the incidence of different variations of the
      spine. MATERIAL AND METHODS: Standardised radiographic examinations of 10,922
      young, healthy pilot aspirants of the German air force were made. Radiographic
      examination included the whole spine in a.p. and lateral projection, the cervical
      spine in oblique projection and in a subunit of 5781 men the lumbar spine in
      oblique projection. RESULTS: The following incidences were found: mild habit
      scoliosis: 80.4%, structural scoliosis: 9%, severe thoracal kyphosis without
      severe lumbar lordosis: 5.1% and together with severe lumbar lordosis: 30.8%,
      mild forms of kyphosis of adolescence: 23.3%, severe forms: 2.1% and cuneiform
      deformation of vertebral body: 4.9%, sacralization: 7.8%, lumbarization: 5.9%,
      spondylolysis: 6.2%, spondylolisthesis: 4.3% and lumbar chondrosis: 2.1%.
      Chondrosis of the thoracal and cervical spine, osteochondrosis and coalescent
      vertebral bodies were found in less than 0.8% each. CONCLUSION: In only 2.6% were
      there no pathological findings. This shows importance of radiological spine
      examinations especially for industrial and preventive medicine.

PMID- 7626751
TI  - [The staging of osteochondritis dissecans in the knee and ankle joints with MR
      tomography. A comparison with conventional radiology and arthroscopy].
AB  - PURPOSE: A prospective study was performed on 50 patients suffering from
      osteochondritis dissecans of the knee and ankle to define criteria for stability
      and fixation of osteochondral lesions. METHODS: Morphological parameters in MRI
      (size, fragmentation, cartilage, interface) and conventional radiology
      (separation, fragmentation) were registered and compared with arthroscopic
      staging. MRI staging based on different types of interfaces was demonstrated on
      T1- and T2-weighted images. RESULTS: MRI could correctly predict a Grade 1 lesion
      in 50%, a Grade 2 lesion in 90%, a Grade 3 lesion in 0%, and a Grade 4 lesion in
      79%. Stable lesions were differentiated from unstable lesions in 90%.
      Radiographic findings corresponded with arthroscopic staging in only 56% of the
      cases because fibrotic connection may guarantee stability in cases of bony
      separation. CONCLUSION: MRI should be performed before therapy to select those
      patients who do not need surgical therapy or arthroscopy.

PMID- 7626753
TI  - [Magnitude contrast angiography in peripheral arterial occlusive disease of the
      lower extremities].
AB  - PURPOSE: To assess the clinical value of magnitude contrast angiography in
      arteriosclerosis of the lower limb. MATERIAL AND METHODS: 187 examinations were
      done in 105 patients with arteriosclerotic lesions of the femoropopliteal
      vessels. The MRA results were compared to DSA and conventional angiography. 36
      patients were investigated before and after angioplasty. RESULTS: Occlusions were
      detected correctly in all cases. In mild and moderate stenoses there was 90%
      agreement. High-grade stenoses may simulate occlusions. All interruptions of the
      signal with a length of 1 to 10 mm have to be read as high-grade stenoses (MRA
      sensitivity was 0.96 and specificity 0.94). In patients with low cardiac output
      MRA may be advantageous in comparison to DSA: collaterals and vessels distal to
      occlusions were visualized better in MRA. Axial scans show morphology of stenoses
      and occlusions and influenced the choice of treatment in 6 cases. In 3 cases,
      thrombotic material and calcified plaque were distinguished. After angioplasty
      vessel wall lesions such as dissection of the intima or compressed plaque inside
      the vessel wall were well visualized. Agreement was 92% with MRA as opposed to
      lesser values with DSA.

PMID- 7626754
TI  - [Magnetic resonance tomography in spinal trauma].
AB  - PURPOSE: To assess the value of MR imaging in the acute and chronic stages of
      spinal trauma. METHODS: 126 MR examinations of 120 patients were evaluated
      retrospectively. In 15 cases of acute spinal cord injury, correlation of MR
      findings with the degree of neurological deficit and eventual recovery was
      undertaken. RESULTS: Cord anomalies in the acute stage were seen in 16 patients.
      Intramedullary haemorrhage (n = 6) and cord transection (n = 2) were associated
      with complete injuries and poor prognosis, whereas patients with cord oedema (n =
      7) had incomplete injuries and recovered significant neurological function. In
      the chronic stage, MR findings included persistent cord compression in 8
      patients, syringomyelia or post-traumatic cyst in 12, myelomalacia in 6, cord
      atrophy in 9, and cord transection in 7 patients. CONCLUSION: In acute spinal
      trauma, MR proved useful in assessing spinal cord compression and instability. In
      addition, direct visualisation and characterisation of post-traumatic changes
      within the spinal cord may offer new possibilities in establishing the prognosis
      for neurological recovery. In the later stages, potentially remediable causes of
      persistent or progressive symptoms, such as chronic spinal cord compression or
      syringomyelia can be distinguished from other sequelae of spinal trauma, such as
      myelomalacia, cord transection or atrophy.

PMID- 7626755
TI  - [A mannitol solution as an oral contrast medium in pelvic MRT].
AB  - PURPOSE: Improvement of pelvic MRI using peroral administration of an aqueous
      mannitol solution. METHODS: We retrospectively evaluated magnetic resonance
      examinations of 72 patients with suspected or proven pelvic abnormalities: In 36
      patients, no bowel marking was carried out. In further 36 patients, we performed
      a contrast enhancement of the bowel by oral application of 1000 ml of an aqueous
      mannitol solution. RESULTS: 8/36 (22%) patients suffered from diarrhoea, nausea
      or meteorism as a result of mannitol application. In group 2, an excellent bowel
      marking of the small intestine could be obtained in 36/36 (100%) patients.
      Contrast enhancement of the bowel significantly improved delineation between
      intestinal structures and pelvic organs or pathologic lesions, respectively. In
      summary, bowel marking was desirable in 25/36 (69%) of group 1 and helpful in
      26/36 (72%) of group 2. CONCLUSION: Aqueous mannitol solution is a safe bowel
      contrast agent and improves the diagnostic value of pelvic MRI, but in some cases
      delineation between marked bowel and cystic pelvic lesions may be uncertain.

PMID- 7626756
TI  - [Intrarenal duplex sonography in detecting flow changes after renal PTA].
AB  - PURPOSE: Changes of the intrarenal Doppler signal were analysed before and after
      renal balloon dilatation to assess the technical success of PTRA. MATERIALS AND
      METHOD: In 33 patients, intrarenal Doppler signal was depicted before and after
      renal PTA. Doppler flow curve was analysed by using the acceleration index (AI),
      acceleration time index (AT) and resistance index (RI); for all indices side
      ratios (AI-R, AT-R and RI-R) were calculated. Balloon dilatation was
      angiographically successful in all cases. Average stenosis graded 71% before and
      21% after PTA. RESULTS: By definition of limits for all indices used, a single
      patient was graded as non-stenotic before balloon dilatation by application of
      AI/AI-R and no patient was graded nonstenotic by AI/RI-R. After renal PTA, all
      indices significantly changed towards normal findings and by application of both
      AI/AI-R and AI/RI-R, only a single patient was graded stenotic after PTA.
      CONCLUSION: Intrarenal Doppler signal analysis reliably allows to detect flow
      changes following renal PTA in patients with renal artery stenosis. It may
      therefore be used as a noninvasive method to monitor flow improvement after renal
      PTA and during follow-up.

PMID- 7626757
TI  - [A new laser puncture guidance device for CT- and MRT-guided punctures of the
      trunk].
AB  - A stereotactic device was developed to facilitate CT- or MR-guided punctures of
      the body. The correct needle angulation is checked by the reflection of fan
      shaped red and green laser beams upon the needle. Due to its principle of
      function and design the device has considerable advantages: The puncture angle
      can be controlled in three dimensions. The freedom of movement within the
      operation area will not be affected. The device does not have to be permanently
      installed and can be employed in MRI at any field strength. Furthermore, all
      kinds of puncture instruments can be used.

PMID- 7626758
TI  - [The rheolytic thrombectomy of an iliac vein].
AB  - As an alternative to thrombolysis, a patient with recent rethrombosis of the
      right iliac vein was successfully recanalized by using a 5 F rheolytic catheter
      system. The patient had undergone bilateral stent recanalisation of the pelvic
      veins after iliocaval thrombosis due to retroperitoneal fibrosis three months
      earlier.

PMID- 7626759
TI  - [Venous stent application with a simultaneous cubitofemoral approach].
AB  - In 4 patients with superior inflow obstruction caused by stenosis or occlusion of
      the central veins it was not possible to pass the guide wire from transfemoral.
      An additional transbrachial access was applied to avoid the stenosis or
      occlusions. Patency of the veins from transbrachial was achieved in all cases.
      After pulling the extensively long guide wire through the still horizontal venous
      lock, successful Wallstent application was performed from transfemoral in all 4
      patients. No peri-interventional or post-interventional complications were seen
      during 2 days follow-up.

PMID- 7626760
TI  - [Hemangioendotheliosarcoma of the kidney].

PMID- 7626761
TI  - [An acinar-cell tumor of the pancreas--an unusual case report].

PMID- 7626762
TI  - [Corticobasal degeneration in computed tomography and magnetic resonance
      tomography--represented by 2 patients].

PMID- 7626763
TI  - [The computed tomographic morphology of Crohn's disease and ulcerative colitis].
AB  - PURPOSE: To assess the value of computed tomography for the diagnosis of Crohn's
      disease and ulcerative colitis. METHOD: We analysed the CT examinations of 109
      patients with 197 involved bowel locations. 81 patients suffered from Crohn's
      disease, 28 from ulcerative colitis. Diagnosis was based on the combination of
      clinical, endoscopic and histopathologic findings. Three radiologists evaluated
      the CT series concerning the presence of morphologic changes analogous to
      conventional radiographic findings. RESULTS: In Crohn's disease, we found
      irregular outer contours in 26% of cases. The bowel wall was thickened in 82%. In
      acute phases, the bowel wall was thickened in 100%. Abscess and fistula as
      complications of inflammatory disease were present in 26 and 14% respectively. In
      ulcerative colitis, a target sign of the bowel wall was present in 40%, whereas
      in Crohn's disease a homogeneous wall density was present in all but two cases.
      Reduced attenuation due to submucosal fat deposits was found in 16% and mucosal
      tunneling in 27% of cases with ulcerative colitis. Even if severe mucosal
      destructions were found, the outer contour of the gut was smooth and regular in
      95% of the ulcerative colitis cases. CONCLUSION: CT can provide additional
      information on acuity, extent and complications in inflammatory bowel disease. In
      combination with conventional radiographic findings a three-step classification
      for Crohn's disease and ulcerative colitis (early changes, acute and chronic
      phase) can be proposed.

PMID- 7626764
TI  - [Rhombencephalosynapsis].

PMID- 7626765
TI  - [The demonstration of a mediastinal parathyroid adenoma with 99m-technetium
      MIBI].

PMID- 7626766
TI  - [A critical comment on the RoFo article 162, 3 (1995) 224-228: The measurement of
      the femoral torsion angle in children by NMR tomography compared to CT and
      ultrasound].

PMID- 7626767
TI  - Therapists and the rehabilitation process after stroke.
AB  - Therapists working in an experimental stroke unit were interviewed about how they
      set goals for rehabilitation, how they measure progress, and about problems of
      discharging patients. In addition the interview covered the topics of quality in
      rehabilitation, the relationship between patient and therapist, and therapists'
      evaluation of the stroke unit. The therapists felt that current outcome
      measurement instruments did not capture the kinds of results that they felt were
      important. They were process-oriented, and not only outcome-oriented as in
      traditional studies of stroke rehabilitation. This explorative study provides an
      insight into how therapists view the stroke rehabilitation process, and
      elaborates themes for future studies of physical and occupational therapy in
      rehabilitation.

PMID- 7626768
TI  - The Purdue Pegboard Test: normative data for people aged 60 and over.
AB  - Manual dexterity is frequently evaluated in rehabilitation services to estimate
      hand function. Several tests have been developed for this purpose, including the
      Purdue Pegboard, which measures fine manual dexterity. The goals of the study
      were to verify the test-retest reliability with subjects aged 60 and over without
      upper limb impairment, and to develop normative data based on a random sample of
      healthy older community-living individuals. The results show that the test-retest
      reliability is good (intra-class correlation coefficients from 0.66 to 0.90,
      depending on the subtest). Norms are presented to help clinicians involved in
      rehabilitation services to better differentiate real dexterity deficits from
      those that may be attributed to normal ageing.

PMID- 7626769
TI  - Disability in late adolescence. III: Utilization of health services.
AB  - Adolescent health service usage is a neglected research area. Data are important
      for planning of services and for prioritizing needs. A sample of 871 18-year-olds
      was surveyed about its use of health services in the preceding year. A
      significant proportion had made a consultation and were mostly satisfied with the
      service received. For a subsample of that cohort, who had a difficulty in their
      daily living, only a third had consulted a health professional for that
      difficulty over the past year. Help-seeking was related to the severity of that
      difficulty, particularly for the limitations that it imposed on everyday life.
      Some dissatisfactions with consultations were expressed in relation to
      expectations of the efficacy of treatment and to the communication of the health
      professionals.

PMID- 7626770
TI  - Description of the US working age disabled populations living in institutions and
      in the community.
AB  - This study provides national estimates of the size of the US working age disabled
      populations in institutions and in the community, and describes these populations
      along a number of dimensions. By using data from the Institutional Population and
      Household Survey Components of the 1987 National Medical Expenditure Survey, the
      study represents the first time that these populations have been studied using
      comparable data. The working age disabled population was identified as persons
      between the ages of 21 and 64 who experienced difficulty with at least one of the
      activities of daily living (ADLs). Using this definition, approximately 1% of the
      total US population was found to be working age disabled (n = 2.6 million). Of
      these, 11% (n = 282,000) resided in long-term care facilities. Significant
      differences were observed between the institutionalized population having mental
      retardation (MR) and those with physical disabilities only. Relative to the MR
      population, members of the physically disabled population had more severe
      limitations in ADLs, entered the facility at a later age, had much shorter stays,
      and were more likely to have a spouse and children who might provide support for
      community-based living. However, some physically disabled persons were admitted
      early in life for very long stays, similar to the situation for most persons with
      MR. Comparisons of the working age disabled populations in institutions and in
      the community showed that those in the community had fewer ADL limitations than
      their institutionalized counterparts and were much more likely to be married.
      Although a surprisingly large proportion of the community-based disabled
      population lived alone (23%), 70% lived with at least one relative.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7626771
TI  - Psychopathological disorders in a population of mentally retarded young adults.
AB  - Nosographic, clinical, therapeutic and psychosocial aspects of psychopathological
      disorders in 43 mentally retarded patients followed from 1988 to 1991 are
      presented. Mental problems in mentally retarded subjects are linked to mental
      illness but do not form a continuum with it. The prognosis is generally
      favourable. Great attention must be given to the psychosocial aspects as social
      integration is almost always at risk in the mentally retarded.

PMID- 7626772
TI  - Do 'social relief' admissions have any effect on patients or their care-givers?
AB  - Dependent patients and their care-givers were studied before and 1 week after a
      social relief admission in order to assess the effects on physical and
      psychological problems. Data about care-givers stress and mental health were
      gathered, as well as patient data. Patients' self-care abilities improved
      slightly but care requirements remained constant. Care-giver stress levels did
      not change, but there was a highly significant improvement in their mental
      health. The results suggest that social relief admissions enabled care-givers to
      continue to look after very dependent people in the community.

PMID- 7626773
TI  - Patient and carer satisfaction in geriatric day hospitals.
AB  - Our objective was to assess the satisfaction of patients who attend geriatric day
      hospitals, and of their carers. We used a convenience sample survey of 92
      patients (mean age 77) and 94 carers of patients attending three geriatric day
      hospitals in Nottingham, England. Patients were interviewed and carers were
      contacted by post. Questionnaires were derived from a regional strategy document
      for the evaluation of day hospital services: 81/92 (88%) patients always liked
      coming to the day hospital and 77/91 (85%) felt that their attendance was always
      worthwhile; 85/89 (96%) of the carers felt that the patient had improved; 74/81
      (91%) of carers felt that they needed the break from caring afforded by the day
      hospital attendance and 74/79 (94%) of carers felt that they personally had
      benefited from it. There was thus a high level of satisfaction with the day
      hospital service among attenders. The role of the day hospital in supporting
      carers is greatly appreciated.

PMID- 7626774
TI  - The Australian RSI debate: stereotyping and medicine.
AB  - The vehement scientific debate which took place in Australia in the 1980s over
      the epidemic of the chronic cervicobrachial pain syndrome known as repetition
      strain injury (RSI) was remarkable for the accompanying social commentary offered
      by many of the medical participants. This commentary was to have a profound
      effect on relationships between individual doctors and their patients with RSI.
      It reflected and reinforced the prevailing stereotypes within Australian society,
      not only of working women, but also of recipients of workers' compensation
      payments. On the other hand, some of the medical responses to the epidemic were
      severely criticized by social scientists who analysed the epidemic. In the
      process of such criticism, a number of stereotypes of doctors were also
      reinforced.

PMID- 7626775
TI  - Bacillus species pseudobacteremia following hospital construction.
AB  - A 13-fold increase (0.08 to 1.05%) in the isolation rate of Bacillus species from
      in-patient blood cultures led to the investigation of pseudobacteremia over a
      four-month period. Data on blood isolates (BACTEC NR 660, bottle types 6A and
      PEDS) of Bacillus species were compiled between July and October 1993. BACTEC
      bottles, as well as their plastic lids and rubber septa (representing 20% of
      stored bottles), and alcohol swabs, iodine preparation pads and butterfly
      collection systems were cultured. Air plates inside the BACTEC 660 instrument
      were cultured, as well as swabs of both the BACTEC needles and the interior of
      the BACTEC handling area. To investigate carry-over contamination, sterile BACTEC
      bottles were tested immediately following bottles containing Bacillus species.
      Growth of Bacillus species was obtained from 16% of the plastic lids and 1.3% of
      the rubber septa. No growth was obtained from other cultures. The outbreak
      coincide with construction on a driveway of the hospital over the area where
      BACTEC bottles were stored. Upon completion of construction in November 1993, the
      isolation of Bacillus species returned to baseline. No pseudobacteremia isolates
      occurred in areas where the trained intravenous team was assigned. In conclusion,
      hospital construction leading to airborne spread of Bacillus species may cause
      Bacillus species pseudobacteremia, and failure to disinfect blood culture bottles
      adequately may predispose to such an outcome.

PMID- 7626776
TI  - Tuberculin skin testing in a hospital and two chronic care facilities in Prince
      Edward Island.
AB  - OBJECTIVE: To determine the prevalence of initial and booster positive responses
      to tuberculin skin testing among staff of an acute care hospital, and among staff
      and residents of two chronic care facilities on Prince Edward Island (PEI).
      PATIENTS AND METHODS: Two hundred and eighty-six staff from the hospital and the
      facilities, and 164 residents from the facilities were given tuberculin testing
      using 5 tuberculin units (TU) of purified protein derivative (PPD) of tuberculin.
      A two-step booster test was performed on 125 of 173 staff (73%) aged 35 years or
      older who initially tested negative, and on 138 of 141 residents (97.9%) at the
      chronic care homes. RESULTS: The overall rate of initial tuberculin positivity
      among staff at the facilities was 15.7%. Among residents, the rate of positivity
      was 14.0%. Histories given by institutional staff of having previously received
      Bacille bilie de Calmette-Guerin vaccine (BCG) were associated with tuberculosis
      (TB) test reactivity, but not with mean reaction size. Staff with a history of
      BCG who tested positive did not differ in age from those testing negative.
      Institutional staff whose work involved patient contact were more likely to have
      a positive test than those whose work did not involve such contact. Booster
      positivity among those older than 35 years of age ranged from 2.0 to 5.2%.
      CONCLUSIONS: These results suggest that, for health care institutions in PEI,
      tuberculin testing should be performed on all new or current hospital staff at
      risk of TB exposure, all new or current staff of chronic care facilities, and all
      new or current residents of chronic care facilities unless contraindicated.
      Booster testing should also be performed on all institutional staff and residents
      35 years of age or older if their initial tuberculin test is negative.

PMID- 7626777
TI  - Patient circuit components of anesthetic equipment between uses on different
      patients.

PMID- 7626778
TI  - Re: glass bead sterilization.

PMID- 7626779
TI  - Workplace Hazardous Materials Information System (WHMIS)

PMID- 7626780
TI  - The codon usage of the nisZ operon in Lactococcus lactis N8 suggests a non
      lactococcal origin of the conjugative nisin-sucrose transposon.
AB  - An 11.6 kb area downstream from the structural gene of nisin Z in the conjugative
      nisin-sucrose transposon of Lactococcus lactis subsp. lactis N8 was cloned and
      sequenced. Analysis of the sequence revealed eight open reading frames,
      nisZBTClPRK, followed by a putative rho-independent terminator (delta G degrees =
      -4.7 kcal/mol). The C-terminal hydrophilic domain of the NisK protein is
      homologous to the C-termini of several histidine kinases of bacterial two
      component regulator systems, such as SpaK from Bacillus subtilis and KdpD and
      RcsC of Escherichia coli. The nisin Z biosynthetic genes were highly similar with
      the genes of the nisin A operons having, however, a 0-3% difference in the amino
      acid sequences of the individual proteins. The codon usage of eleven genes within
      the same conjugative transposon was calculated and found to be strikingly
      different from that of other lactococcal genes. This, together with the low GC
      content (32%) compared to the 38% (G+C) of the lactococcal chromosome in general
      strongly suggests a non-lactococcal origin of this transposon.

PMID- 7626781
TI  - Complete sequence of a 38.4-kb human cosmid insert containing the polymorphic
      marker DXS455 from Xq28.
AB  - The complete DNA sequence of a cosmid mapping to human Xq28 (DXS455) has been
      determined using a shotgun approach (genbank accession number: L31948). The
      cosmid insert is 38.4 kb in length, and contains several repetitive sequences,
      including a highly repetitive region located in a fragment previously shown to
      contain a polymorphic VNTR locus, as well as short di- and tri-nucleotide
      repeats. In addition to the previously known VNTR locus, a CA-repeat and an
      unusual 800-bp repetitive region have been found to be polymorphic. The repeated
      sequence mapping to the site of the VNTR locus spans 480 bp in the cosmid. In
      addition to several AT-dinucleotide stretches, this repeat has four copies of a
      25 bp repeat unit and flanking sequences similar to this 25-mer. No expressed
      sequences have so far been identified in this cosmid.

PMID- 7626782
TI  - Sequence of Asr2, a member of a gene family from Lycopersicon esculentum encoding
      chromosomal proteins: homology to an intron of the polygalacturonase gene.
AB  - Asr is a family of genes regulated by abscisic acid, stress and ripening in
      tomato. Asr2, a recently reported member of this family, has been further
      characterized through sequencing of a genomic clone. We report the sequencing of
      2029 bp of Asr2, spanning its AT-rich (62%) upstream region with probable
      regulatory functions. This region displays several candidate TATA and CAAT boxes
      that might be involved in transcription initiation, as well as a motif similar to
      one previously reported to be responsible for induction by ABA. Apart from that,
      we found a 108-bp stretch from the 3' non-coding region which displays a high
      homology (92%) to a region within intron 6 of the polygalacturonase gene, which,
      like Asr2, is expressed in ripening tomato fruit. This striking similarity
      suggests the presence of either a conserved regulatory motif or an abundant
      mobile element.

PMID- 7626783
TI  - Sequence of cassava ribulose-1,5-bisphosphate carboxylase small subunit precursor
      cDNA.
AB  - The cDNA sequence of cassava ribulose-1,5-bisphosphate carboxylase small subunit
      rbcS precursor has been determined. The cassava rbcS precursor cDNA contains 266
      nucleotides (nts) of 5' untranslated region, 546 nts of coding region, 280 nts of
      3' untranslated region and a poly (A) tail of 70 nts. The 5' untranslated region
      is characterized by some unusual features which include two plausible open
      reading frames, several repeated sequences and a putative Shine-Dalgarno
      sequence. The predicted amino acid sequence shows that the precursor consists of
      a 59 amino acid transit peptide followed by the 123 amino acid rbcS sequence.
      Cassava rbcS shares 82% amino acid sequence identity with a rubber rbcS sequence.

PMID- 7626784
TI  - Molecular cloning and sequence of bovine Msx-1 homeobox-containing gene cDNA from
      a bovine odontoblast library.
AB  - Screening of a bovine odontoblast cDNA library from developing incisor with
      murine Msx-1 and Msx-2 cDNA probes led to the isolation of three positive clones.
      All of them encoded for a sequence of a protein containing 297 amino acids. The
      responsible gene was designated as bovine Msx-1 (bMsx-1) due to the high homology
      with the human MSX-1 and mouse Msx-1 sequences.

PMID- 7626785
TI  - Generation of 28 sequence-tagged sites (STSs) from yeast artificial chromosome
      (YAC) clones anchored at human chromosome 21q22.1 region.
AB  - Twenty-eight sequence-tagged sites (STSs) were newly generated from the DNA
      sequences of vector-insert junctions from yeast artificial chromosomes (YACs)
      anchored at chromosome 21q22.1 region. The insert DNAs adjacent to vector arms
      were specifically amplified through inverse PCR method to clone into pUC19 vector
      for sequencing. Sixty DNA junctions from 44 CEPH YAC clones were cloned and
      sequenced. Of these DNA sequences of junctions between vector-arms and DNA
      inserts, twenty-eight STSs were finally obtained to show the accurate
      amplification, which is specific for human chromosome 21. The sets of 28 STSs
      were useful to build fine YAC contigs by STS-mediated YAC walking at the 21q22.1
      region.

PMID- 7626786
TI  - Conservation of the hypersensitivity-pathogenicity regulatory gene hrpX of
      Xanthomonas campestris and X. oryzae.
AB  - The hrpX gene is essential for pathogenicity of Xanthomonas species. Loss of hrpX
      by mutation results in the loss of pathogenicity and a gain in the ability of
      Xanthomonas to cause the hypersensitive response in their respective host plants,
      suggesting that hrpX confers a means to evade this host defense response. The
      function of HrpX protein was predicted by sequencing of hrpXc and hrpXo from X.
      campestris pv. campestris and X. oryzae, respectively. The predicted amino acid
      sequences of the protein encoded by these respective genes revealed similarities
      (45.96%) to the HrpB protein of Burkholderia solanacearum, which has sequence
      identity to the transcriptional activator VirF of Yersinia enterocolitica and
      AraC of Escherichia coli. Thus, HrpX may regulate Xanthomonas virulence genes
      since a putative DNA binding domain present in the carboxyl terminal half of HrpX
      is highly conserved among HrpB, VirF and AraC and since over-expression of the
      carboxyl terminal half of HrpX in E. coli is lethal.

PMID- 7626787
TI  - Assignment of Borrelia burgdorferi strains G25 and VS461 to the Borrelia garinii
      and Borrelia afzelii genospecies, respectively: a comparison of OspA protein
      sequences.
AB  - The nucleotide sequence encoding the Outer Surface Protein A (OspA) from two
      Borrelia burgdorferi sensu lato isolates, G25 and VS461, has been determined. On
      the basis of a phylogenetic analysis, strains G25 and VS461 were respectively
      assigned to the B. garinii and B. afzelii genospecies. Comparative analysis of
      OspA proteins from 26 different B. burgdorferi sensu lato strains involved in
      Lyme disease indicated a higher heterogeneity in the B. garinii genospecies than
      in the two other genospecies, B. burgdorferi sensu stricto and B. afzelii.

PMID- 7626788
TI  - Nucleotide sequence of the ovine P53 tumor-suppressor cDNA and its genomic
      organization.
AB  - A 2155 bp cDNA clone corresponding to the ovine p53 tumor suppressor gene has
      been isolated from a cDNA library made from the BLV-transformed YR2 cell line
      RNA. After the sequencing analysis, it appeared that this clone contains the
      entire p53 coding region (including 126 bp upstream of the ATG initiation codon).
      The nucleotide sequence shows a high degree of homology with the human (73%),
      murine (74%) and rat (66%) cDNAs. The encoded ovine p53 protein is 382 amino
      acids long with an apparent molecular weight of 50 kDa and shares 79% and 72%
      amino acid homology with the human and the mouse p53 respectively. Furthermore,
      the homology is not equally distributed along the molecule but is mainly located
      within five highly conserved regions. As its mouse and human counterparts, the
      ovine p53 contains a high proportion of proline residues, an acidic N-terminal
      domain and a basic C-terminal domain. We also report the structure of the ovine
      p53 gene that is similar to those already defined from other species.

PMID- 7626789
TI  - Nucleotide sequence of the bovine P53 tumor-suppressor cDNA.
AB  - The bovine p53 open reading frame was cloned and characterized using a reverse
      transcription-polymerase chain reaction amplification (RT-PCR) method. After
      sequencing, it appeared that this cDNA is able to code for a 386 amino acids
      protein with high degree of homology with the ovine p53. Furthermore, the
      homology is not equally distributed along the molecule since the highest
      divergence is located within the exon 4. The bovine p53 shares 93% and 91%
      homology with the ovine p53 at the DNA and protein level respectively.

PMID- 7626790
TI  - Novel mouse endothelial cell surface marker is suppressed during differentiation
      of the blood brain barrier.
AB  - Few markers specific for mouse endothelium exist. We describe here one such
      marker, MECA-32, a monoclonal antibody which shows high specificity for mouse
      endothelium in both embryonic and mature tissues. The MECA-32 antigen has a M(r)
      of 50-55 x 10(3) under reducing conditions and M(r) of 100-120 x 10(3) under
      nonreducing conditions. It is expressed on most endothelial cells in the
      embryonic and in the adult mouse, with the exception of the brain, skeletal, and
      cardiac muscle, where it has a more restricted distribution. In skeletal and
      cardiac muscle only small arterioles and venules express the MECA-32 antigen,
      while in the brain its expression is negatively correlated with the
      differentiation of the vasculature to form the blood brain barrier.
      Interestingly, during embryonic development the antigen occurs on the brain
      vasculature up to day 16 of gestation (E16), whereupon it disappears. The
      embryonic brain is an avascular organ anlage which is vascularized by ingrowth of
      external blood vessels. Differentiation of the vasculature to form the blood
      brain barrier occurs at approximately E16 in the mouse. This differentiation
      correlates with the downregulation of MECA-32 antigen expression. Between E12 and
      E16 MECA-32 detects most endothelial cell surfaces of the blood vessels in the
      brain. No MECA-32 antigen is found in the brain at E17 or any later stage of
      development with the exception of the vasculature of the circumventricular
      organs. The results suggest that MECA-32 antigen expression is temporally and
      spatially correlated with the development of the blood brain barrier.

PMID- 7626791
TI  - FGF-2 mRNA and its antisense message are expressed in a developmentally specific
      manner in the chick limb bud and mesonephros.
AB  - FGF-2 protein is present in the ectoderm and mesoderm of the developing chick
      limb bud. Its importance has been shown by the ability of ectopically applied FGF
      2 to replace the apical ectodermal ridge, allowing complete outgrowth and
      subsequent pattern formation of the limb bud. The first goal of this study was to
      determine whether FGF-2 mRNA was present in the same ectodermal and mesodermal
      regions of the chick embryo as FGF-2 protein. FGF-2 also has an antisense message
      that is convergently transcribed from the opposite DNA strand (Kimelman and
      Kirschner [1989] Cell 59:687-696; Volk et al. [1989] EMBO J. 8:2983-2988). The
      second goal was to demonstrate the expression and distribution of the antisense
      message. Using RNAse protection assays we detected a full length protected
      fragment that corresponds to chick embryo FGF-2 mRNA, and a partially protected
      fragment that corresponds to the antisense message. We used in situ hybridization
      to show that FGF-2 mRNA was present in the ectoderm and subjacent mesoderm of the
      chick wing bud. FGF-2 mRNA was also present in body ectoderm and undifferentiated
      mesoderm throughout the embryo, and in muscle cells, dorsal neural tube, and
      mesonephros. In situ hybridization also revealed evidence for the presence of the
      natural antisense message in the embryo in most, but not all, of the same regions
      as the FGF-2 mRNA. FGF-2 mRNA and its antisense message colocalized in
      undifferentiated limb mesoderm; however, antisense message was not detected in
      differentiated muscle or cartilage. It is important to note that FGF-2 mRNA was
      always present in the mesonephros but that the antisense message was never
      observed in the mesonephros, thereby providing an internal control for non
      specific signal. Although little is known about its function, Kimelman and
      Kirschner ([1989] Cell 59: 687-696) proposed that the antisense message may
      increase turnover of FGF-2 mRNA. When we compared the in situ hybridization data
      of both mRNAs with levels of FGF-2 protein (Savage et al. [1994] Dev. Dyn.
      198:159-170), interesting tissue specific patterns emerged that support this
      hypothesis.

PMID- 7626792
TI  - Expression pattern of the murine LIM class homeobox gene Lhx3 in subsets of
      neural and neuroendocrine tissues.
AB  - Murine Lhx3 cDNA isolated from the mouse pituitary cDNA library encodes a LIM
      type homeodomain protein that contains two tandemly repeated LIM domains and the
      homeodomain. The identities of predicted amino acid sequences between the mouse
      of Lhx3 and Xenopus Xlim-3 genes are 80, 95, and 97% in the LIM domains 1 and 2,
      and the homeodomain, respectively, and 84% in the entire protein. 5'-RACE
      procedures and genomic cloning revealed that two distinct N-terminal sequences
      arise from two different exons 1a and 1b. Exon 1a encodes a sequence similar to
      that of Xlim-3, whereas exon 1b encodes a different N-terminus. It is likely that
      there are two transcription initiation sites in the Lhx3 gene. The Lhx3
      transcripts were detected by whole mount in situ hybridization as early as day
      E9.5 post coitum in Rathke's pouch and the closing neural tube. During subsequent
      development, Lhx3 expression was observed in the anterior and intermediate but
      not in the posterior lobes of the pituitary, and in the ventral hindbrain and
      spinal cord. Northern blot analysis of adult tissues showed that Lhx3 mRNA
      persists in the pituitary. The expression pattern of Lhx3 is well conserved
      between Xenopus and mouse, underscoring the functional importance of this gene as
      a regulator of development. A number of established cell lines of pituitary
      origin express Lhx3 and therefore constitute a useful tool for further study of
      Lhx3 gene function.

PMID- 7626793
TI  - Muscle cell death during the development of head and neck muscles in the chick
      embryo.
AB  - Degenerating myofibers have been reported in the embryos and neonates of a number
      of birds and mammals, but neither the pervasiveness of the phenomenon nor the
      spatio-temporal patterns of degeneration has been examined in detail. Using
      transmission electron microscopy, we determined the patterns of muscle cell death
      in the chick biventer cervicis, a head extensor muscle. Cell death is most
      pronounced at incubation days 10 through 15, and occurs throughout the muscle.
      This is the period during which many myofiber clusters segregate into individual
      fibers, each with a separate basal lamina, and secondary myofibers become
      demarcated. Cells of largest diameter, presumably the primary myofibers, are
      preferentially affected. Degenerating cells exhibit a cohort of cytological
      features consistent with apoptosis, including the presence of dense, darkly
      staining, hypercontracted myofibrils, misshapen nuclei with irregular chromatin
      condensations along the nuclear envelope, and scores of cytoplasmic vesicles and
      vacuoles. In cross section some large diameter muscle cells are characterized by
      sparse, flocculent cytoplasm that is devoid of myofibrils and organelles. Some
      show disintegrating cell membranes. In longitudinal section 200-300 microns long
      regions of hypercontracted myofibrils alternate with areas devoid of fibrils;
      this arrangement suggests that the myofibrils break into segments that are in
      register along one part of a muscle fiber and entirely absent from the adjacent
      length of fiber. We have observed similar patterns of muscle cell degeneration in
      the complexus, splenius cervicis, depressor mandibulae, and branchiomandibularis
      muscles. By day 18 of incubation most signs of degeneration are absent and by
      hatching (day 21) the muscle fibers all appear healthy. Many of these cytological
      changes in embryonic head muscle cells are characteristic of programmed cell
      death. We hypothesize that large-scale death of myocytes is a normal part of
      avian myogenesis and an important mechanism for affecting the transformation from
      embryonic to hatching muscle patterning.

PMID- 7626794
TI  - Re-programming of expression of the KGFR and bek variants of fibroblast growth
      factor receptor 2 during limb regeneration in newts (Notophthalmus viridescens).
AB  - We have previously shown, by in situ hybridization, that fibroblast growth factor
      receptor 2 (FGFR2) is present in the basal layer of wound epithelium during limb
      regeneration in newts (Notophthalmus viridescens). In contrast, FGFR1 expression
      is observed throughout the blastema mesenchyme but is distinctly absent from the
      wound epithelium (Poulin et al. [1993] Development 119:353-361). Sequence
      analysis revealed that we have isolated both the KGFR and bek variants of FGFR2.
      These two variants differ only in the second half of the last of their three (or
      two) Ig-like domains. In this report, we show the expression patterns of FGFR2
      variants during limb regeneration by in situ hybridization. During the pre
      blastema stages of regeneration, FGFR2 expression was observed in the basal layer
      of the wound epithelium and in the cells of the periosteum. The wound epithelial
      hybridization was observed when the KGFR-specific probe was used while the bek
      specific probe hybridized to mRNA in the cells of the periosteum. As regeneration
      progresses to the blastema stages, KGFR expression continued to be observed in
      the basal layer of the wound epithelium with additional hybridization seen in the
      blastema mesenchyme closely associated with the bisected bones. The bek-specific
      hybridization pattern observed at this stage corresponds specifically to the
      mesenchymal hybridization. In the differentiation stages of regeneration, the
      mesenchymal expression of FGFR2 becomes restricted to the cells of the condensing
      cartilage and later to the perichondrium. Interestingly, there appears to be a
      dorsoventral gradient of the expression of both KGFR and bek variants of FGFR2,
      which are opposite each other at the later stages of regeneration. Thus, re
      programming of expression of the two FGFR2 variants is required during the
      initial wound closure of limb regeneration. Remarkably, the expression patterns
      of KGFR and bek mimic those observed in the mouse limb bud during early embryonic
      development (Orr-Urtreger et al. [1993] Dev. Biol. 18:475-486). Moreover, our
      results suggest that the two FGFR2 variants have distinct roles in limb
      regeneration. Further investigation regarding the potential sources of the FGF
      ligands will help establish the roles that FGFs and FGFRs play in limb
      regeneration.

PMID- 7626795
TI  - 92-kDa type IV collagenase and TIMP-3, but not 72-kDa type IV collagenase or TIMP
      1 or TIMP-2, are highly expressed during mouse embryo implantation.
AB  - Expression of 72 kDa and 92 kDa type IV collagenases and the metalloproteinase
      inhibitors TIMPs 1, 2, and 3 was studied by in situ hybridization in implanting
      mouse embryos of days 5.5 to 7.5. The 92 kDa type IV collagenase was strongly
      expressed in invading trophoblasts, signals above background not being observed
      in the embryonic proper or placental tissue. In contrast, signals above
      background were not seen for the 72 kDa enzyme in any cells of the implantation
      region, including trophoblasts and stromal cells of the decidual tissue. Only
      cells in the mucosal stroma outside the decidual region displayed some
      expression. TIMP-3 was intensily expressed in maternal cells in the area
      surrounding the invading embryonic tissue. No expression was observed for TIMP-1
      or TIMP-2 in the embryo proper, trophoblasts, or the area of the uterine decidual
      reaction. Weak signals appeared for TIMP-1 only in the circular layer of
      myometrial smooth muscle and in some uterine stroma cells distant from the site
      of embryo implantation. The results suggest a central role for 92 kDa type IV
      collagenase and TIMP-3 in the extracellular proteolysis associated with
      implantation of the early embryo.

PMID- 7626796
TI  - Alpha 6 subunit of integrins in the development and sex differentiation of the
      mouse ovary.
AB  - The localization of the alpha 6 subunit of integrins in the ovary was studied by
      conventional and immunolabeling light and electron microscopy starting from the
      pregonadal embryonic phase until adulthood. The formation of gonadal blastema
      cells included an initial expression of the alpha 6 subunit on the plasma
      membranes of all blastema cells. Subsequently the reaction for the alpha 6
      subunit became restricted in groups of these cells, which differentiated into
      gonadal cord cells, the precursors of follicular cells. The alpha 6 subunit was
      also found in the cells of the mesonephric duct, mesonephric tubules, and the
      ovarian rete. Reorganization of the gonadal cords into follicles at birth was
      accompanied with strong and uniform re-expression of the alpha 6 subunit on the
      surface of the cord cells. Vascular endothelial cells and the cells of the
      postnatal surface epithelium remained positive for the alpha 6 integrin subunit.
      In larger follicles, the intensity of the reaction for the integrin subunit
      varied. The theca cells of growing follicles contained the alpha 6 subunit. The
      results show that this subunit of integrins is present in phases of increased
      adhesion and aggregation, and that its expression probably is involved in the
      regulation of ovarian epithelial differentiation. The distribution of alpha 6
      integrin in ovarian cells shows potentially important sex-specific and
      developmental differences in epithelial organization when compared with
      respective changes found earlier by us in the male gonad.

PMID- 7626797
TI  - Epithelial cell polarity in early Xenopus development.
AB  - The Xenopus blastula consists of two morphologically distinct cell types.
      Polarized epithelial cells build up the embryonic surface and fence off an inner
      non-polarized cell population. We examined the establishment of this early
      functional cell diversification in the embryo by single cell analysis, in vitro
      cell culture, and transplantation experiments. Single blastomeres from a 64-cell
      embryo (1/64 cells) exhibit several features of polarized cells. The plasma
      membrane of 1/64 cells consists of an apical domain, which is inherited from the
      original egg membrane, and a basolateral domain derived from newly formed
      membrane during cleavage. These are inherent, cell-autonomous properties of the
      blastomeres, as they form and are maintained in blastomeres raised in the absence
      of any cell interactions in calcium free medium. Upon in vitro culture a single
      1/64 cell gives rise to an aggregate of two different cell types. Cells carrying
      a part of the former egg membrane domain differentiate into polarized epithelial
      cells, whereas cells lacking this membrane domain are not polarized. These
      results demonstrate that the inclusion of the egg membrane, rather than external
      signals related to the position of a cell in the intact embryo, is required for
      the apical/basolateral differentiation of the surface epithelium. This view is
      supported by cell transplantation studies. A single 1/64 cell was implanted into
      the blastocoel of a stage 8 blastula embryo. The progeny of the implanted cell
      proliferate within the host embryo and split into two morphologically distinct
      populations with different cell behaviours. Cells incorporating a part of the egg
      membrane form coherent patches of polarized epithelial cell sheets in the
      interior of the host embryo. In contrast, cells lacking egg membrane do not
      exhibit any characteristics of polarized cells and eventually spread into
      different regions of the host embryo. Our results show that the egg membrane
      and/or components of the submembrane cortex play a determinative role in the
      formation of the blastula epithelium.

PMID- 7626798
TI  - Involvement of extracellular matrix in the formation of the inner ear.
AB  - Formation of the inner ear from the optic placode differs from invagination of
      other cup-shaped organ primordia. Activation of the actin cytoskeleton seems to
      play a limited role because precocious invagination does not occur upon treatment
      with activators of a contractile event and cannot be prevented by inhibitors. In
      this study, the possibility that invagination is mediated by changes in the
      surrounding mesenchyme was tested by treating embryos with agents which interfere
      with the integrity of extracellular matrix. Enzymes degrading hyaluronate and/or
      chondroitin sulfate were microinjected into the otic region prior to folding.
      Synthesis of chondroitin sulfate proteoglycan was inhibited by microinjection of
      beta-xyloside. All treatments inhibited otic pit formation by interfering with
      fold formation within the placode. Immunocytochemical procedures showed depletion
      of the appropriate extracellular matrix components for a short time period after
      enzyme treatments and for up to 24 hr after beta-xyloside injection. Invagination
      of the otic primordium is concluded to be controlled in part by anchorage of the
      epithelium to adjacent structures and possibly by expansion of the mesenchymal
      extracellular matrix.

PMID- 7626799
TI  - Postembedding colloidal-gold immunocytochemistry of noncollagenous extracellular
      matrix proteins in mineralized tissues.
AB  - Immunocytochemistry is a powerful tool for investigating protein secretion,
      extracellular matrix assembly, and cell-matrix and matrix-matrix/mineral
      relationships. When applied to the tissues of bones (bone and calcified
      cartilage) and teeth (dentin, cementum, and enamel), where calcium phosphate
      containing extracellular matrices are the predominant structural component
      related to their weight-bearing and masticatory roles, respectively, data from
      immunocytochemical studies have been prominent in advancing our understanding of
      mineralized tissue modeling and remodeling. The present review on the application
      of postembedding, colloidal-gold immunocytochemistry to mineralized tissues
      focuses on the advantages of this approach and relates them to conceptual,
      theoretical, and experimental data currently available discussing matrix-mineral
      interactions and extracellular matrix formation and turnover in these tissues.
      More specifically, data are summarized regarding the distribution and role of
      noncollagenous proteins in different mineralized tissues, particularly in the
      context of how they interface with mineral, and how this relationship might be
      affected by the various tissue-processing steps and immunocytochemical strategies
      commonly implemented to examine the distribution and function of tissue proteins.
      Furthermore, a technical discussion is presented that outlines several different
      possibilities for epitope exposure in mineralized tissues during preparation of
      thin sections for transmission electron microscopy. Cell biological concepts of
      protein secretion by cells of the mineralized tissues, and subsequent
      extracellular matrix assembly and organization, are illustrated by examples of
      high-resolution, colloidal-gold immunolabeling for osteopontin, bone
      sialoprotein, and osteocalcin in the collagen-based mineralized tissues and for
      enamel protein (amelogenin) in enamel.

PMID- 7626800
TI  - Immunocytochemistry of plant defense mechanisms induced upon microbial attack.
AB  - During the past few years, cyto- and immunocytochemical techniques have been
      developed and widely used for locating and identifying various molecules in plant
      cell compartments. The last decade has witnessed tremendous improvements in
      molecular cytology, thus allowing an accurate in situ detection of various
      components thought to play important biological functions in the plant
      metabolism. The use of immunocytochemistry to investigate resistance mechanisms
      of plants upon pathogen attack has provided key information on the defense
      strategy that plants elaborate during a host-pathogen interaction. Of the various
      proteins induced in response to infection, chitinases and beta-1,3-glucanases
      have been the focus of particular attention due to their believed antimicrobial
      activity through the hydrolysis of the main fungal wall components, chitin and
      beta-1,3-glucans. Attention has also been paid to beta-fructosidase, the enzyme
      that hydrolyzes sucrose into glucose and fructoside. The marked accumulation of
      this enzyme upon pathogen infection has led to the consideration that infection
      may greatly influence the metabolic activity of colonized tissues by creating
      alterations of source-sink relationships. Another facet of the plant's defense
      strategy that has been the focus of considerable interest is related to the
      accumulation of structural compounds, such as hydroxyproline-rich glycoproteins
      and callose, to reinforce the wall architecture, thus decreasing vulnerability to
      microbial enzymes. A number of alternatives designed to improve plant protection
      towards pathogen invasion have been suggested. Among these, the production of
      transgenic plants expressing constitutively a foreign resistance gene and the
      pretreatment of plants with elicitors of defense reactions have been the subject
      of intensive studies at the molecular, biochemical, and cytological levels.
      Results of such studies clearly demonstrate the important contribution that cyto-
      and immunocytochemical approaches can make to our knowledge of how plants defend
      themselves and how plant disease resistance can be directly enhanced. These
      approaches will undoubtedly be active areas for future research in the
      development of biological control alternatives in which the mode of action of the
      product used is of key importance.

PMID- 7626801
TI  - Immunogold studies on peroxisomes: review of the localization of specific
      proteins in vertebrate peroxisomes.
AB  - Peroxisomes, since their discovery as microbodies, have been studied mostly
      independently by electron microscopists and biochemists. The fine structure has
      been studied by electron microscopy, and the compositional enzymes and proteins
      by protein biochemistry. Electron microscopic histochemistry has been used to try
      to clarify the relationship between the fine structure and its constituents. The
      immunogold technique, a combination of electron microscopy and protein
      biochemistry, for the first time resolved this problem due to the high
      sensitivity and resolution power of the staining and the high reliability of the
      technique. The present paper reviews the way in which the immunogold techniques,
      especially the protein A-gold technique, revealed the localization of various
      enzymes or proteins in peroxisomes or peroxisomal subcompartments, and discusses
      why this technique should be employed in peroxisome research.

PMID- 7626802
TI  - SEM comparison of Morpho butterfly dorsal and ventral scales.

PMID- 7626803
TI  - mRNA transport in yeast: time to reinvestigate the functions of the nucleolus.
AB  - Nucleocytoplasmic transport of mRNA is vital to gene expression and may prove to
      be key to its regulation. Genetic approaches in Saccharomyces cerevisiae have led
      to the identification of conditional mutants defective in mRNA transport.
      Mutations in approximately two dozen genes result in accumulation of transcripts,
      trapped at various sites in the nucleus, as detected by in situ hybridization.
      Phenotypic and molecular analyses of many of these mRNA transport mutants suggest
      that, in yeast, the function of the nucleus is not limited to the biogenesis of
      pre-ribosomes but may also be important for transport of poly(A)+ RNA. A similar
      function of the animal cell nucleolus is suggested by several observations.

PMID- 7626804
TI  - The Wee1 protein kinase regulates T14 phosphorylation of fission yeast Cdc2.
AB  - The Cdc2 protein kinase is a key regulator of the G1-S and G2-M cell cycle
      transitions in the fission yeast Schizosaccharomyces pombe. The activation of
      Cdc2 at the G2-M transition is triggered by dephosphorylation at a conserved
      tyrosine residue Y15. The level of Y15 phosphorylation is controlled by the Wee1
      and Mik1 protein kinases acting in opposition to the Cdc25 protein phosphatase.
      Here, we demonstrate that Wee1 overexpression leads to a high stoichiometry of
      phosphorylation at a previously undetected site in S. pombe Cdc2, T14. T14
      phosphorylation was also detected in certain cell cycle mutants blocked in
      progression through S phase, indicating that T14 phosphorylation might normally
      occur at low stoichiometry during DNA replication or early G2. Strains in which
      the chromosomal copy of cdc2 was replaced with either a T14A or a T14S mutant
      allele were generated and the phenotypes of these strains are consistent with T14
      phosphorylation playing an inhibitory role in the activation of Cdc2 as it does
      in higher eukaryotes. We have also obtained evidence that Wee1 but not Mik1 or
      Chk1 is required for phosphorylation at this site, that the Mik1 and Chk1 protein
      kinases are unable to drive T14 phosphorylation in vivo, that residue 14
      phosphorylation requires previous phosphorylation at Y15, and that the T14A
      mutant, unlike Y15F, is recessive to wild-type Cdc2 activity. Finally, the normal
      duration of G2 delay after irradiation or hydroxyurea treatment in a T14A mutant
      strain indicates that T14 phosphorylation is not required for the DNA damage or
      replication checkpoint controls.

PMID- 7626805
TI  - Inhibition of cyclin-dependent kinases by p21.
AB  - p21Cip1 is a cyclin-dependent kinase (Cdk) inhibitor that is transcriptionally
      activated by p53 in response to DNA damage. We have explored the interaction of
      p21 with the currently known Cdks. p21 effectively inhibits Cdk2, Cdk3, Cdk4, and
      Cdk6 kinases (Ki 0.5-15 nM) but is much less effective toward Cdc2/cyclin B (Ki
      approximately 400 nM) and Cdk5/p35 (Ki > 2 microM), and does not associate with
      Cdk7/cyclin H. Overexpression of P21 arrests cells in G1. Thus, p21 is not a
      universal inhibitor of Cdks but displays selectivity for G1/S Cdk/cyclin
      complexes. Association of p21 with Cdks is greatly enhanced by cyclin binding.
      This property is shared by the structurally related inhibitor p27, suggesting a
      common biochemical mechanism for inhibition. With respect to Cdk2 and Cdk4
      complexes, p27 shares the inhibitory potency of p21 but has slightly different
      kinase specificities. In normal diploid fibroblasts, the vast majority of active
      Cdk2 is associated with p21, but this active kinase can be fully inhibited by
      addition of exogenous p21. Reconstruction experiments using purified components
      indicate that multiple molecules of p21 can associate with Cdk/cyclin complexes
      and inactive complexes contain more than one molecule of p21. Together, these
      data suggest a model whereby p21 functions as an inhibitory buffer whose levels
      determine the threshold kinase activity required for cell cycle progression.

PMID- 7626806
TI  - Mutation or deletion of the Saccharomyces cerevisiae RAT3/NUP133 gene causes
      temperature-dependent nuclear accumulation of poly(A)+ RNA and constitutive
      clustering of nuclear pore complexes.
AB  - To identify genes whose products play potential roles in the nucleocytoplasmic
      export of messenger RNA, we isolated temperature-sensitive strains of
      Saccharomyces cerevisiae and examined them by fluorescent in situ hybridization.
      With the use of a digoxigen-tagged oligo-(dT)50 probe, we identified those that
      showed nuclear accumulation of poly(A)+ RNA when cells were shifted to the
      nonpermissive temperature. We describe here the properties of yeast strains
      bearing the rat3-1 mutation (RAT-ribonucleic acid trafficking) and the cloning of
      the RAT3 gene. When cultured at the permissive temperature of 23 degrees C, fewer
      than 10% of cells carrying the rat3-1 allele showed nuclear accumulation of
      poly(A)+ RNA, whereas approximately 70% showed nuclear accumulation of poly(A)+
      RNA, whereas approximately 70% showed nuclear accumulation of poly(A)+ RNA after
      a shift to 37 degrees C for 4 h. In wild-type cells, nuclear pore complexes
      (NPCs) are distributed relatively evenly around the nuclear envelope. Both
      indirect immunofluorescence analysis and electron microscopy of rat3-1 cells
      indicated that NPCs were clustered into one or a few regions of the NE in mutant
      cells. Similar NPC clustering was seen in mutant cells cultured at temperatures
      between 15 degrees C and 37 degrees C. The RAT3 gene encodes an 1157-amino acid
      protein without similarity to other known proteins. It is essential for growth
      only at 37 degrees C. Cells carrying a disruption of the RAT3 gene were very
      similar to cells carrying the original rat3-1 mutation; they showed temperature
      dependent nuclear accumulation of poly(A)+ RNA and exhibited constitutive
      clustering of NPCs. Epitope tagging of Rat3p demonstrated that it is located at
      the nuclear periphery and co-localizes with nuclear pore proteins recognized by
      the RL1 monoclonal antibody. We refer to this nucleoporin as Rat3p/Nup133p.

PMID- 7626809
TI  - Colorectal disease in the '90s.

PMID- 7626807
TI  - Integrin alpha 8 beta 1 promotes attachment, cell spreading, and neurite
      outgrowth on fibronectin.
AB  - The integrin alpha 8 subunit, isolated by low stringency hybridization, is a
      novel integrin subunit that associates with beta 1. To identify ligands, we have
      prepared a function-blocking antiserum to the extracellular domain of alpha 8,
      and we have established by transfection K562 cell lines that stably express alpha
      8 beta 1 heterodimers on the cell surface. We demonstrate here by cell adhesion
      and neurite outgrowth assays that alpha 8 beta 1 is a fibronectin receptor.
      Studies on fibronectin fragments using RGD peptides as inhibitors show that alpha
      8 beta 1 binds to the RGD site of fibronectin. In contrast to the endogenous
      alpha 5 beta 1 fibronectin receptor in K562 cells, alpha 8 beta 1 not only
      promotes cell attachment but also extensive cell spreading, suggesting functional
      differences between the two receptors. In chick embryo fibroblasts, alpha 8 beta
      1 is localized to focal adhesions. We conclude that alpha 8 beta 1 is a receptor
      for fibronectin and can promote attachment, cell spreading, and neurite outgrowth
      on fibronectin.

PMID- 7626810
TI  - The war on drugs: an alternative approach.

PMID- 7626808
TI  - Selective translocation of protein kinase C-delta in PC12 cells during nerve
      growth factor-induced neuritogenesis.
AB  - The specific intracellular signals initiated by nerve growth factor (NGF) that
      lead to neurite formation in PC12 rat pheochromocytoma cells are as of yet
      unclear. Protein kinase C-delta (PKC delta) is translocated from the soluble to
      the particulate subcellular fraction during NGF-induced-neuritogenesis; however,
      this does not occur after treatment with the epidermal growth factor, which is
      mitogenic but does not induce neurite formation. PC12 cells also contain both
      Ca(2+)-sensitive and Ca(2+)-independent PKC enzymatic activities, and express
      mRNA and immunoreactive proteins corresponding to the PKC isoforms alpha, beta,
      delta, epsilon, and zeta. There are transient decreases in the levels of
      immunoreactive PKCs alpha, beta, and epsilon after 1-3 days of NGF treatment, and
      after 7 days there is a 2.5-fold increase in the level of PKC alpha, and a 1.8
      fold increase in total cellular PKC activity. NGF-induced PC12 cell
      neuritogenesis is enhanced by 12-O-tetradecanoyl phorbol-13-acetate (TPA) in a
      TPA dose- and time-dependent manner, and this differentiation coincides with
      abrogation of the down-regulation of PKC delta and other PKC isoforms, when the
      cells are treated with TPA. Thus a selective activation of PKC delta may play a
      role in neuritogenic signals in PC12 cells.

PMID- 7626813
TI  - Colon cancer screening: the case for sigmoidoscopy.

PMID- 7626811
TI  - Unclean, unclean....

PMID- 7626812
TI  - A physician is a physician is a physician....

PMID- 7626814
TI  - Inflammatory bowel disease and its association with colorectal cancer.

PMID- 7626815
TI  - CEA: is it of value in colorectal cancer?

PMID- 7626816
TI  - Changes in the overall management of rectal carcinoma.

PMID- 7626817
TI  - Rubber band ligation of hemorrhoids.
AB  - A retrospective review of 384 patients who had undergone rubber band ligation for
      hemorrhoidal disease by one surgeon from 1988 to 1993 is presented. The primary
      indications for treatment were rectal bleeding and prolapse. Eighty-nine percent
      of the patients were improved following treatment. In selected patients, rubber
      band ligation is an acceptable alternative to surgical hemorrhoidectomy.

PMID- 7626818
TI  - Colorectal cancer mortality in Rhode Island.

PMID- 7626819
TI  - Increased middle cerebral artery flow velocity during the initial phase of
      cardiopulmonary bypass may cause neurological dysfunction.
AB  - One hundred twenty-seven patients undergoing coronary artery bypass graft surgery
      were monitored by transcranial Doppler ultrasonography. Five patients had more
      than 50% increases in middle cerebral artery mean flow velocity during the
      initial phase (10-120 sec) of cardiopulmonary bypass. Four of these 5 developed
      neurological complications including stroke and encephalopathy. These results
      indicate that overperfusion of the basal cerebral arteries during cardiopulmonary
      bypass procedures may contribute to neurological dysfunction after the surgery.

PMID- 7626820
TI  - Interictal single-photon emission computed tomography in partial epilepsy.
      Accuracy in localization and prediction of outcome.
AB  - The role of interictal brain single-photon emission computed tomography (SPECT)
      was examined using (99mTc)- labeled hexamethylpropyleneamine oxime (HMPAO) in
      refractory partial epilepsy. The accuracy with which SPECT localized an epileptic
      focus and whether it predicted long-term postoperative seizure relief were
      assessed. Twenty patients were evaluated, 14 of whom ultimately had anterior
      temporal lobectomy with follow-up ranging from 41 to 56 months. A single-headed
      gamma camera was used. The interictal SPECT showed ipsilateral temporal
      hypoperfusion in 8 (47%) of 17 patients with temporal lobe epilepsy and showed
      either multilobar hypoperfusion or no perfusion defects in the rest. The
      sensitivity and specificity were similar in patients with a more complex clinical
      picture who required intracranial electrodes and those who did not. Presence or
      absence of temporal lobe hypoperfusion did not correlate with postoperative
      seizure relief. It is concluded that interictal SPECT with 99mTc-HMPAO with a
      single-headed gamma camera does not add useful information in preoperative
      localization or predicting postoperative seizure relief.

PMID- 7626821
TI  - HMPAO single-photon emission computed tomography in posterior circulation
      infarcts.
AB  - The sensitivity of single-photon emission computed tomography (SPECT) in
      evaluating posterior circulation infarcts compared with that of computed
      tomography (CT) or magnetic resonance imaging (MRI) remains unknown. In a
      hospital-based population, the authors studied SPECT, CT, and MRI in 35
      consecutive patients presenting with acute infarction clinically localized in the
      thalamus (7), posterior cerebral artery (PCA) territory (15), brainstem (19), and
      cerebellum (3). Multiple infarcts were noted in 8 patients. Overall, the SPECT
      sensitivity was lower than that of MRI (21% vs 93%, p = 0.004) and CT (42% vs
      65%, p = 0.046). The SPECT and CT sensitivities were not significantly different
      (67% vs 73%) for PCA infarcts. Performed within 24 hours, SPECT showed a relevant
      hypoperfusion in all PCA infarcts. For brainstem infarcts, CT (33%, p = 0.074)
      and MRI (91%, p = 0.004) were more sensitive than SPECT, which showed no
      hemispheric hypoperfusion. The sensitivity of the three imaging techniques was
      100% for large cerebellar infarcts. For the small group of thalamic infarcts, the
      SPECT, CT, and MRI sensitivities were 14, 71, and 100%, respectively. Thus, SPECT
      compared to CT and MRI is not helpful in the subacute phase to localize PCA and
      cerebellar infarcts and is of limited value for thalamic infarcts. In the first
      hours, the absence of cerebral hypoperfusion in brainstem infarcts may help to
      differentiate them from hemispheric infarcts usually associated with profound
      hypoperfusion.

PMID- 7626822
TI  - Color-coded ultrasound diagnosis of vascular occlusion in acute ischemic stroke.
AB  - A combination of extracranial and transcranial color-coded sonography was used to
      identify the patterns of vascular occlusion in 47 patients with acute ischemic
      stroke. Total anterior circulation infarction (n = 20) was associated with
      internal carotid artery (ICA) or middle cerebral artery (MCA) occlusion (n = 8
      and 9, respectively), or with significant reduction in ipsilateral MCA velocities
      (n = 5). Patients with partial anterior circulation (n = 22) infarction had
      patency of the ipsilateral ICA and MCA. In this group, significant reduction of
      ipsilateral MCA velocities (n = 7) was associated with more extensive infarcts on
      conventional neuroimaging (n = 6), suggesting multiple MCA branch occlusions.
      Ultrasound imaging was unable to identify underlying vascular pathology in
      patients with posterior circulation infarction or with lacunar infarction (n =
      5). An ultrasound-based approach enables noninvasive identification of major
      vascular pathology of the anterior cerebral circulation in patients with acute
      cerebral infarction. It may be useful for the rapid identification of patients
      most and those least likely to benefit from acute intervention, and for
      monitoring their response.

PMID- 7626823
TI  - Localized in vivo 1H magnetic resonance spectroscopy and in vitro analyses of
      heterogeneous brain tumors.
AB  - Results of magnetic resonance spectroscopic (MRS) studies of the chemical
      patterns in brain tumors have been inconsistent. Actual biochemical correlations
      are needed. In 2 patients with heterogeneous intracranial tumors, in vivo 1H MRS
      and in vitro biochemical analyses were correlated. Histology confirmed the tumor
      heterogeneity. Choline was elevated in the cellular portion of both tumors but
      decreased in the necrotic or cystic portions. Creatine was diffusely decreased
      while lactate was elevated in all regions of both tumors. Furthermore, the
      increase in the choline peak on 1H MRS appeared to be due to increases in water
      soluble choline compounds. This study illustrates the value of small localized
      voxels for differentiating regional chemical differences in tumors.

PMID- 7626824
TI  - Basilar artery dolichoectasia. Review of the literature and six patients studied
      with magnetic resonance angiography.
AB  - Six patients for whom computed tomography revealed a curvilinear calcific mass
      anterior to their brainstem were evaluated and magnetic resonance imaging and
      magnetic resonance angiography were performed on each. Magnetic resonance studies
      confirmed the suspicion of basilar artery dolichoectasia, and demonstrated a
      partial thrombus in the basilar artery in 1 patient. The patients' clinical
      features were combined with those of basilar artery dolichoectasia patients
      reported in the literature (n = 122) who had case histories sufficiently detailed
      enough to determine each person's mode of clinical presentation. Basilar artery
      dolichoectasia patients were more often men (95/128, 74%) and had a mean age of
      59 +/- 11 years. Of the 128 patients studied, there were cranial nerve
      compressive signs in 74 (58%), especially facial spasm (29/74, 39%) and
      trigeminal neuralgia (20/74, 27%); vertebral basilar insufficiency or vertebral
      basilar stroke or both in 61 (48%); hydrocephalus in 40 (31%); compressive
      brainstem symptoms and signs that progressed clinically in 31 (24%); and arterial
      hypertension in 31 (24%). Magnetic resonance imaging and magnetic resonance
      angiography safely diagnose this interesting arterial abnormality. The modes of
      clinical presentation of this disorder are reviewed.

PMID- 7626825
TI  - Automatic magnetic resonance tissue characterization for three-dimensional
      magnetic resonance imaging of the brain.
AB  - Computer-assisted diagnostic systems enhance the information available from
      magnetic resonance imaging. Segmentations are the basis on which three
      dimensional volume renderings are made. The application of a raw data-based,
      operator-independent (automatic), magnetic resonance segmentation technique for
      tissue differentiation is demonstrated. Segmentation images of vasogenic edema
      with gross and histopathological correlation are presented for demonstration of
      the technique. A pixel was classified into a tissue class based on a feature
      vector using unsupervised fuzzy clustering techniques as the pattern recognition
      method. Correlation of fuzzy segmentations and gross and histopathology were
      successfully performed. Based on the results of neuropathological correlation,
      the application of fuzzy magnetic resonance image segmentation to a patient with
      a brain tumor and extensive edema represents a viable technique for automatically
      displaying clinically important tissue differentiation. With this pattern
      recognition technique, it is possible to generate automatic segmentation images
      that display diagnostically relevant neuroanatomical and neuropathological tissue
      contrast information from raw magnetic resonance data for use in three
      dimensional volume reconstructions.

PMID- 7626826
TI  - Reduced temporal lobe glucose metabolism in aging.
AB  - The results of a positron emission tomography study of regional cerebral
      metabolic rates of glucose are reported for 8 healthy old subjects (mean age, 66
      yr; standard deviation [SD], 5) and 9 young subjects (mean age, 27 yr; SD, 4.6)
      using a high-resolution positron emission tomograph and the glucose metabolic
      tracer 18F-fluorodeoxyglucose. Older subjects showed significantly lower cerebral
      metabolic rates than did the young subjects, in anterior, middle, and posterior
      temporal neocortex and in mesial temporal cortex, with the largest differences
      occurring in anterior temporal cortex (temporal pole). The current findings may
      reflect either decreases in regional cerebral metabolic rates for glucose that
      occur with normal aging, or early indications of cognitive dysfunction that is
      associated with age-related disorders.

PMID- 7626827
TI  - Kinetics of elimination and acute consequences of cerebral air embolism.
AB  - The pathophysiology of arterial air embolism inducing brain injuries remains
      unclear. Previous experiments demonstrated the usefulness of computed tomography
      (CT) in the detection of air emboli in canine brain. This canine study
      investigates CT's ability to detect small air bubbles and to determine the
      kinetics of air elimination from cerebral arteries and its relationship with
      clinical, electroencephalographic (EEG), and histological manifestations. CT
      detects small air embolism, and intracerebral air volume strongly correlates with
      injected air dose (r2 = 0.86, p = 2 x 10(-3)). Air clearance time significantly
      depends on intracerebral air volume (r2 = 0.86, p = 0.04) and on the number of
      bubbles (r2 = 0.71, p = 0.03), whereas half-life of air elimination does not. No
      relationship was found between injected air dose, air clearance time,
      intracerebral volume of air, and clinical, EEG, and histological findings. The
      data indicate that CT accurately detects small air bubbles in the early course of
      cerebral air embolism, that air elimination from cerebral arteries follows a
      first-order compartment model, and that early CT findings do not correlate with
      clinical, EEG, and histological manifestations.

PMID- 7626828
TI  - Herpes simplex myelitis simulating neoplasm on magnetic resonance imaging.

PMID- 7626829
TI  - Cervical (C2) herpes zoster infection followed by pontine infarction.
AB  - This article reports a man who had herpes varicella zoster cervicalis with
      delayed stroke in the posterior circulation. Empiric treatment was acyclovir,
      methylprednisolone, and aspirin. Pontine infarction involving migration of the
      virus via cervicovascular innervation from C2 dorsal root ganglia to the
      vertebrobasilar circulation with attendant angiitis/angiopathy and thrombosis is
      proposed.

PMID- 7626830
TI  - Embolic pontine infarction in a nonhypertensive patient following coronary
      angioplasty.
AB  - A 63-year-old woman was found to have decreased vibration, light touch, and
      proprioception sensations in the right hemi-body, following cardiac angioplasty.
      The patient was not hypertensive although she had a history of
      hypercholesterolemia and was a smoker. Magnetic resonance images of the brain
      demonstrated abnormal signal intensity in the left paramedian basis pons anterior
      to the fourth ventricle. The lesion was believed to be consistent with a lacunar
      infarction. Unlike this woman, the majority of patients who have a small-vessel
      stroke are usually diabetic or hypertensive. The interesting features here were
      that the stroke was a complication of coronary angioplasty, was cardioembolic to
      the pons, and was falsely localized to the thalamus. In addition, rarely does an
      embolic stroke involve a single brainstem tract.

PMID- 7626831
TI  - Carotid steal syndrome: a case study.
AB  - The progression of subclavian arterial stenosis and the subsequent formation of
      collateral pathways serve to alter the pressure gradients in subclavian steal
      syndrome, altering ipsilateral vertebral artery flow from its normal state to
      "latent," "transient," and "continuous" steals. A similar altered flow in the
      carotid arteries can be observed with stenosis of the proximal common or
      innominate artery. A 59-year-old man was seen in the vascular laboratory for
      evaluation of symptomatic peripheral arterial disease. An incidental asymptomatic
      stenosis of the right innominate and left proximal subclavian artery was found.
      Further cerebral vascular evaluation displayed a continuous right subclavian
      steal and a latent steal in the right internal carotid artery. Transcranial
      Doppler examination displayed "transient" steal in the terminal right internal
      carotid artery. Combining duplex and transcranial Doppler evaluations allows
      sequential evaluation of the progression of arterial disease and its effect on
      the flow patterns in the cerebral vasculature.

PMID- 7626832
TI  - SPECT imaging of stroke.
AB  - Single-photon emission computed tomography (SPECT) is a helpful tool for the
      management of stroke patients. Brain perfusion SPECT can help differentiate an
      ischemic event from peri-ictal phenomena such as Todd's paresis. Initial data
      suggest that SPECT may be useful in prognosticating the likelihood of an early
      stroke after a transient ischemic attack and in distinguishing lacunar from
      cortical stroke. After an acute stroke, early SPECT depicts the area of ischemia
      with greater accuracy than either computed tomography or magnetic resonance
      imaging. When the perfusion defect is large, the likelihood of hemorrhagic
      complications or herniation increases. Reperfusion of an arterial territory after
      thrombolysis can be documented more conveniently with SPECT than with
      angiography. SPECT before and after the injection of acetazolamide has been used
      to assess the vascular reserve in patients with severe stenosis of the proximal
      vessels of the cerebrovascular tree. Combined with transcranial Doppler studies,
      SPECT is used to document ischemia after subarachnoid hemorrhage. It has also
      been used to assess the effect of arterial ligation intended to treat
      arteriovenous malformations or aneurysms on brain perfusion and to evaluate
      ischemia secondary to pressure from an intracranial hemorrhage.

PMID- 7626833
TI  - SPECT functional brain imaging. Technical considerations.
AB  - The technical aspects of functional brain single-photon emission computed
      tomography (SPECT) imaging, referring primarily to the most common SPECT brain
      function measure--regional cerebral blood flow--are reviewed. SPECT images of
      regional cerebral blood flow are influenced by a number of factors unrelated to
      pathology, including tomographic quality, radiopharmaceuticals, environmental
      conditions at the time of radiotracer administration, characteristics of the
      subject (e.g., age, sex), image presentation, and image processing techniques.
      Modern SPECT scans yield excellent image quality, and instrumentation continues
      to improve. The armamentarium of regional cerebral blood flow and receptor
      radiopharmaceuticals is rapidly expanding. Standards regarding the environment
      for patient imaging and image presentation are emerging. However, there is still
      much to learn about the circumstances for performances and evaluation of SPECT
      functional brain imaging. Challenge tests, primarily established in
      cerebrovascular disease (i.e., the acetazolamide test), offer great promise in
      defining the extent and nature of disease, as well as predicting therapeutic
      responses. Clearly, SPECT brain imaging is a powerful clinical and research tool.
      However, SPECT will only achieve its full potential in the management of patients
      with cerebral pathology through close cooperation among members of the nuclear
      medicine, neurology, psychiatry, neurosurgery, and internal medicine specialties.

PMID- 7626834
TI  - SPECT in epilepsy.

PMID- 7626835
TI  - The clinical role of SPECT in patients with brain tumors.

PMID- 7626836
TI  - Viral infections of the brain.
AB  - Brain infections are generally well visualized by contrast-enhanced computed
      tomography or magnetic resonance imaging. However, these modalities are often
      unrevealing in the encephalopathy produced by the human immunodeficiency virus
      and in the early stages of herpes simplex encephalitis. Several studies have
      documented the greater sensitivity of perfusion single-photon emission computed
      tomography (SPECT) in human immunodeficiency virus encephalopathy. In herpes
      simplex encephalitis, a few case reports have documented that SPECT may depict
      increased perfusion in the characteristically involved temporal and other limbic
      structures when computed tomography and magnetic resonance imaging are normal.

PMID- 7626837
TI  - SPECT perfusion imaging in the diagnosis of dementia.
AB  - Single-photon emission computed tomography (SPECT) imaging has provided the
      practicing clinician with a method of studying brain function in patients with
      dementia. A large and growing number of papers report the experiences of a number
      of laboratories in the use of this technique in the evaluation of demented
      patients. Studies from several laboratories comparing patients with Alzheimer's
      disease to control subjects report sensitivity and specificity of SPECT perfusion
      imaging to be in the 80% vicinity. In addition, a number of studies suggest that
      the dementias that show the greatest similarities in perfusion patterns to
      Alzheimer's disease are multi-infarct dementia and dementia associated with
      Parkinson's disease. Although considerable data exists to guide the physician, a
      rigorous scientific approach to studying patients in a prospective, unselected
      clinical sample, with autopsy confirmation of the diagnosis, is needed to define
      clearly the utility of the technique in diagnosing dementias.

PMID- 7626838
TI  - Head trauma: use of SPECT.
AB  - Brain damage inflicted by head trauma may not be visible on computed tomography
      or magnetic resonance imaging. This is true not only for mild head trauma, but
      also for moderate and severe head trauma. Perfusion imaging with single-photon
      emission computed tomography has proved in several controlled studies to be more
      sensitive than either computed tomography or magnetic resonance imaging in
      detecting brain abnormalities in patients with head trauma.

PMID- 7626839
TI  - [Conformal radiation therapy. Federation nationale des centres de lutte contre le
      cancer (FNCLCC)].
AB  - The authors present the summary of a workshop of a group of radiation oncologists
      and radiation physicists on three dimensional treatment planning and conformal
      radiation therapy with multileaf collimator. It appears that this technic must be
      considered as experimental and that it cannot be promoted in all radiotherapy
      departments without scientific and clinical evaluation.

PMID- 7626840
TI  - [Clinical value of the potential doubling time (Tpot) measured by flow
      cytometry].
AB  - The potential doubling time (Tpot) is defined as the time necessary to double the
      number of proliferating tumor cells in the absence of spontaneous cell loss. Tpot
      is thought to be a better index of tumor proliferation than clinically observed
      tumour volume doubling time. The in vivo measurement of Tpot is a possible way to
      detect fast growing tumours which would be better controlled by accelerated
      radiotherapy. The published data demonstrate the feasibility and the safety of
      the technique. Large variations in Tpot values were observed in tumors with
      similar histology, indicating an accelerated proliferation rate in some tumors.
      There are technical difficulties related to intra-tumor heterogeneity, sample
      contamination by normal cells, and inter-laboratory variability, which question
      the biological interpretation of Tpot. Further studies are ongoing to establish
      whether the in vivo measurement of Tpot 1) provides information that is
      independent of the "classical" prognostic factors, and 2) allows the early
      recognition of the patients likely to benefit from accelerated treatment.

PMID- 7626841
TI  - [Identification of human carcinogenic risks in IARC monographs].
AB  - For more than twenty years, the IARC has been evaluating the carcinogenic risk to
      humans of chemicals, groups of chemicals, complex mixtures, occupational
      exposures, behavioral and life-style exposures, biological agents, such as
      bacteria and viruses, and physical agents, such as radiation, on the basis of
      published studies of carcinogenicity in humans and laboratory animals. This paper
      includes the list established by IARC of substances carcinogenic to humans.

PMID- 7626842
TI  - [Detection of the resistance to Ara-C blast cells in acute myeloid leukemia using
      flow cytometry].
AB  - Ara-C is currently used in the treatment of adult acute myeloid leukemia (AML).
      The cytotoxicity of Ara-C derives from an inhibition of DNA synthesis which can
      be determined using flow cytometry from the amount of bromodeoxyuridine (BrdUrd)
      incorporated into cells after a short exposure to BrdUrd. We developed a computer
      program to quantify inhibition of the rate of DNA synthesis by analysis of the
      distribution of BrdUrd/DNA. A resistance index (RI) was expressed as the ratio of
      the amount of BrdUrd incorporated into S phase cells incubated with Ara-C to that
      incorporated in the absence of Ara-C. In Ara-C sensitive and resistant HL60 cell
      lines, a linear relationship between RI and log Ara-C concentration was observed.
      This technique was applied to 96 bone marrow samples from patients with de novo
      AML treated by a regimen containing Ara-C. A first group of nine patients with
      high RI values included only drug resistant (DR) patients; a second group of 63
      patients with low RI values included 62 patients who achieved a complete
      remission (CR); a third group of 24 patients with intermediate RI values included
      19 CR and five DR patients. In view of these results, we think that it is
      possible to detect a majority of DR patients treated by Ara-C.

PMID- 7626843
TI  - [Association of Epstein-Barr virus and Hodgkin's disease: comparison between
      Algerian and French patients].
AB  - The prevalence of Epstein-Barr virus (EBV) markers in nodal lesions from Algerian
      (Al) patients (n = 47) was compared to French (Fr) patients (n = 21) with
      Hodgkin's disease. Initial characteristics were: males Fr 57%, Al 53%; median age
      Fr 29, Al 26; histologic subtypes: lymphocytic predominance (LP) Fr 1, Al 2;
      nodular sclerosis (NS) Fr 16, Al 19; mixed cellularity (MC) Fr 4, Al 12;
      lymphocytic depletion (LD) Al 2. The latent membrane protein (LMP) was expressed
      in Reed-Sternberg cells (RSC) in 16 Al (4 NS, 12 MC) and 4 Fr (2 NS, 2 MC) cases.
      All LMP-positive cases were also positive by DNA or RNA in situ hybridization
      (ISH). ISH was positive in RSC of 29% of Fr and 66% of Al patients (p < 0.02);
      the positivity was more frequent in MC (80%) than in other histologic types
      (39%). EBV genome was detected by PCR on DNA extracted from frozen samples in 84%
      of Fr and 95% of Al patients (100% of MC and 86% of other histologic types). The
      discrepancy between PCR and ISH results can be due to a lesser sensitivity of the
      latter technique, or, alternatively, to the presence of EBV in lymphoid cells
      surrounding RSC. ISH positivity was more frequent in young Al adults than in Fr
      ones. This more pronounced HD-EBV link in patients from a developing country
      compared with an industrialized one can result from the age at primary EBV
      infection, which occurs earlier in Algeria than in France.

PMID- 7626844
TI  - [Prognostic evaluation of small cell lung carcinoma by flow cytometry. A
      retrospective study from bronchial brushing samples].
AB  - The authors determined the desoxyribonucleic acid (DNA) content of 45 small-cell
      lung cancers, by flow-cytometry (FC), from bronchial brushings to asses the
      prognostic meaning of the DNA index, the percentage of cells in DNA synthesis
      phase (% S) and the ploidy. Moreover, the value of this tumorous cells brushing
      was assessed for Flow-cytometric analysis. Bronchial brushing offers some
      advantages opposite to biopsies, but the low quantity of collected cells reduces
      the number of tumors analysable by FC. The output is low (39%) for determination
      of DNA index, and moreover low (22%) for determination of % S. In regard to the
      flow-cytometry analysis, the DNA content does not show any significant difference
      of survival where as the % S is related to survival, but it seems to be
      paradoxical in this study. Indeed, patients with small-cell lung cancer
      associated to high cells' percentage in DNA synthesis phase have the longest
      survival.

PMID- 7626845
TI  - [Simultaneous radiochemotherapy in locally advanced cancers of the cervix: a
      preliminary study].
AB  - We have designed a combined treatment strategy of bifractionated split course
      radiotherapy (RT) and concomitant chemotherapy (CT) to try to improve the results
      of RT in inoperable cervical carcinoma. After evaluation, patients were submitted
      to further radical surgery or additional RT-CT depending on the treatment
      results. Between January 1988 and January 1992, 25 patients with non metastatic
      inoperable disease entered in the protocol. The stage of the disease was: T3N0 4
      patients, T3 with hydronephrosis seven patients, T3N1 12 patients, and T4N0 two
      patients. Nineteen patients received two courses of CT with fluorouracil (F),
      cisplatin (P) with or without etoposide. Pelvic RT was given twice daily (two
      fractions of 3 Gy) on days 1, 3, 15 and 17. A combination of F 400 mg/m2/d and P
      15 mg/m2/d in continuous infusion with oral etoposide (100 mg/d) and hydroxyurea
      (500 mg/d) in 11 patients was delivered concomitantly on days 1-3 and 14-17. A
      clinical and radiological evaluation was performed four weeks later. Patients
      with objective response underwent radical hysterectomy (group A) and those with
      incomplete response received additional RT-CT protocol (group B). All patients
      had endocavitary brachytherapy at the end of treatment. After two cycles of CT
      there were four PR in 19 patients and 5 failures. After RT-CT there were 12 CR
      (48%) and eight PR. There was a relationship between disease status after RT-CT
      and response to initial CT in those 19 patients who received the neoadjuvant CT.
      Fifteen patients were in group A, six of whom had no histologically active
      disease in the post-operative sample. However all 15 patients were rendered free
      of disease. Ten patients were in group B, five of whom attained the clinical CR
      status. In total, 20 of 25 patients (80%) were in CR at the end of treatment. Six
      patients experienced pelvic recurrence and two patients distant metastases. Four
      of the five patients with incomplete response had evolutive disease. The overall
      survival is 60% and 36% at 1 and 2 years respectively after a median follow-up of
      22 months (14-48 m). The protocol was tolerable. These results compare favorably
      with those of conventional RT and warrant further evaluation.

PMID- 7626846
TI  - [Pelvic lymph node invasion in cancer of the uterine cervix].
AB  - Pelvic lymph node invasion is an important prognostic factor for cervical cancer.
      It is generally accepted that iliac lymph nodes must be treated systematically,
      but the extent of lymph node dissections is open to discussion. One hundred and
      eighty two cases of cervical cancer with lymph node invasion were treated at the
      Institut Curie between 1960 and 1988, by colpohysterectomy with lymph node
      dissection (168 cases) combined with preoperative brachytherapy and, in some
      cases, pre- and/or postoperative radiotherapy; in 14 cases, only an exploratory
      operation was performed. External iliac lymph node invasion was found in 95% of
      cases, situated in the middle and internal chains. Common iliac lymph node
      invasion was found in 24% of cases, but was only exceptionally isolated (3%). It
      is therefore possible, by means of well defined, localized external iliac
      dissection, with frozen section histological examination, to determine the exact
      lymph node status. Lumboaortic lymph node invasion was found in 8.2% of cases.
      The overall survival rate was 49% at 5 years and 40.5% at 10 years. Factors which
      influence survival are: the cervical volume (p = 0.015), the unilateral or
      bilateral nature of invasion (p = 0.0015), the number of lymph nodes invaded (two
      or more than two) (p = 0.0001), capsular rupture (p = 0.0008), lymph node
      adhesions other than venous (p = 0.0002), common iliac invasion (p = 0.0001). On
      Cox's model, the principal factors were the number of lymph nodes invaded,
      adhesion other than venous, common iliac invasion; on the other hand, venous
      adhesion does not modify the prognosis. The five-year survival rates following
      external iliac dissections and complete pelvic dissections were not significantly
      different. Finally, postoperative radiotherapy ensured a higher five-year
      survival rate than preoperative radiotherapy, but the cervical volume was greater
      and primary invasion was more frequent in these cases. Postoperative radiotherapy
      of 15 grays after preoperative radiotherapy did not appear to modify the survival
      and therefore appears to be useless.

PMID- 7626847
TI  - [Prostatic tumors (adenoma, adenocarcinoma) and obesity in Cameroon].
AB  - The aim of this study was to look for an association between obesity and
      prostatic tumors in general in Cameroon. During a sixteen month period (1
      September 1991 to 31 December 1992), we recruited 50 symptomatic patients with
      histologically confirmed prostatic tumors who were matched with a control of the
      same age. Of these patients, 36 had adenomas, 12 had carcinomas, two had both
      tumors. Patients' age ranged from 49 to 91 years. The difference in body weight
      and height between the patients and the controls was not significant. According
      to the Lorentz formula, there were as many obese patients as controls. Obesity
      was five times more frequent in the patients than the controls following the body
      mass index, but this difference was not significant. We conclude that in our
      area, there might be an association between obesity and prostatic tumors in
      general but our study is too small to reach a conclusion.

PMID- 7626848
TI  - [Dose intensity in anticancer chemotherapy. Paris, 19 December 1994].

PMID- 7626849
TI  - Platinum dose-intensity in solid tumors: pharmacological and clinical
      perspectives.

PMID- 7626850
TI  - [Importance of the initial chemotherapy dose in the treatment of small cell lung
      carcinoma: therapeutic perspectives].
AB  - Treatment of patients with small-cell lung cancer (SCLC) remains disappointing
      despite high initial complete response rates. The dramatic initial
      chemosensitivity of tumor cells is frustrated by the early emergence of
      chemoresistant clonogenic cells, regardless of front line treatments. Although
      the dose relationship is fairly well established regarding the response rate, its
      effect on survival is inconclusive. From 1980 to 1988, 202 patients with limited
      SCLC were included in four consecutive protocols using an alternating schedule of
      thoracic radiotherapy and chemotherapy. Despite an increase of chemotherapy
      and/or total radiation doses, no significant difference was observed between the
      four protocols in terms of response rate, disease free and overall survival.
      However, a retrospective analysis performed on a total of 131 consecutive
      patients led us to propose the hypothesis that a moderate increase in the initial
      dose, ie first course, of cisplatin and cyclophosphamide could improve overall
      survival. From 1988 to 1991, 105 patients were subsequently included in a large
      randomized trial raising this question. The treatment difference only concerned
      the initial doses of cisplatin (80 vs 100 mg/m2) and cyclophosphamide (900 vs
      1200 mg/m2). The trial was closed after inclusion of 105 patients, 32 months
      after the start of the study because at that time overall survival was
      significantly better in the higher-dose group (p = 0.001). The emergence of this
      debatable concept opens new directions in the therapeutic strategy of SCLC and
      the contribution of hematopoietic growth factors may be of great interest in the
      management of this disease.

PMID- 7626851
TI  - [Chrono-chemotherapy and dose intensity].
AB  - Circadian (about 24 h) changes modulate cellular metabolism and proliferation in
      healthy tissues. As a result, the extent of toxicity of cancer chemotherapy
      varies by 50% or more according to dosing time in mice or rats. These
      experimental data led to test the principle of adapting chemotherapy delivery to
      circadian rhythms--so-called "chronotherapy"--in cancer patients. Clinical trials
      first aimed to assess toxicities and maximal tolerated dose of chronotherapy
      schedules. Programmable-in-time pumps became the indispensable tool for reliably
      testing this principle in a large enough patient population and without any need
      for hospitalization. Results from randomized clinical trials have indicated that
      chronotherapy allowed to increase dose intensity (DI, a secondary criterion in
      these trials) by 13 to 45% as compared to injecting the drug at another time
      (doxorubicin, cisplatin) or according to a flat rate (5-fluorouracil,
      floxuridine, oxaliplatin). A non-randomized trial further suggested this
      principle would also apply to cytokine delivery (interferon alpha). Two
      consecutive randomized trials have revealed that chronotherapy-related increase
      in 5-FU DI was further associated with a 20% increase in response rate of
      patients with metastatic colorectal cancer to the 3-drug association that was
      used (5-FU, folinic acid and oxaliplatin). In a subsequent phase II trial 5-FU
      daily dose and 3-drug treatment frequency were increased in 50 patients with this
      disease. Such intrapatient dose escalation protocol also disclosed a positive
      correlation between DI of 5-FU and response. New anticancer drugs should benefit
      from this approach so that both their clinical safety and patient's quality of
      life are improved, through ambulatory administration.

PMID- 7626852
TI  - [Dose intensity in cancer chemotherapy: definition, average relative dose
      intensity and effective dose intensity].
AB  - The cytotoxic activity of cancer chemotherapy is related to the dose and to the
      amount of drug delivered per time unit. The significance of time in the
      effectiveness of a treatment program is frequently overlooked. The term of dose
      intensity (DI) is used to define the drug dose delivered per time unit and is
      expressed as mg/m2 per week. A delay in the sequence of treatment cycles
      decreases the DI in the same proportion as a reduction of dose. Average relative
      DI corresponds to the mean DI of combined agents and is expressed as a fraction
      of a similar combination selected as a standard. DI is useful to compare the dose
      actually received with the prescribed dose. The relation of DI with tumor
      response or survival has not been fully demonstrated. A threshold DI level for
      therapeutic activity is evident. Above this threshold, a linear relationship of
      DI and effectiveness is not obvious, particularly regarding high-dose
      chemotherapy. The term of DI is more useful in its principle than in the
      significance of its calculated value.

PMID- 7626853
TI  - [Increase of dose intensity by pharmacomodulation. General concepts and
      therapeutic applications].
AB  - There are two distinct levels where dose intensity can be increased by
      pharmacomodulation. The first level implies the inhibition of clearly identified
      resistance mechanisms. Among them, MDR type resistance is the most studied
      currently. MDR resistance is mediated by GP170, a cell membrane protein, which
      can be inhibited by several pharmacological agents like verapamil, ciclosporine
      and S 9788 which are currently being clinically investigated. The inhibition of
      DNA repair mechanisms is another approach and a representative example is the
      inhibition of O6-alkylguanine DNA alkyltransferase by O6-methylguanine or O6
      benzylguanine. Modulation of detoxification pathways has also been considered,
      with for instance, the use of buthionine sulfoximide (BSO) to deplete
      intracellular glutathione levels. The second level for pharmacomodulation
      concerns pharmacological interferences with metabolic pathways controlling the
      activity of anticancer agents and particularly the antimetabolites like ara-C and
      5-FU. The use of hydroxyurea or PALA in the case of 5-FU are good illustrations
      of pharmacomodulation via specific metabolic routes. Finally, the 5-FU-folinic
      acid combination could characterise a third level of pharmacomodulation where
      cytotoxic activity is optimised at the site of interaction between activated drug
      (5FdUMP) and target (thymidilate synthase).

PMID- 7626854
TI  - [Hematopoietic growth factors (choice, chronology, combination].
AB  - Hematopoietic growth factors (HGF) or blood stem cell (BSC) transplantation can
      be used to decrease hematological toxicity due to high dose radio-chemotherapy.
      HGF can also be combined to BSC transplantation in different ways: administered
      either alone (during the steady state) or combined standard chemotherapy, HGF can
      increase BSC mobilisation and consequently the yield of BSC collected leading to
      a decrease of aplasia duration after transplantation; administered to the patient
      after transplant, they can decrease the period of granulocytopenia; HGF can also
      be used to expand ex vivo BSC before reinfusion to the patient. In these
      different situations, the best combination of HGF needs to be clarified.

PMID- 7626855
TI  - [Experience with non-Hodgkin's lymphoma].
AB  - High-dose chemotherapy with autologous bone-marrow transplantation is active in
      non-Hodgkin lymphoma patients. The results of randomized trials in the setting of
      consolidation of first complete remission are not in favor of use of high-dose
      chemotherapy. However preliminary results of pilot studies are in favor of this
      treatment in reponder patients. The results of the PARMA protocol will help to
      answer the question.

PMID- 7626856
TI  - Intensive chemotherapy with stem cell support-experience in pediatric solid
      tumours.
AB  - A recent Consensus Conference in Lyon reviewed the role of high-dose therapy with
      stem cell rescue in a variety of malignancies including childhood tumours. The
      conclusion was that with the exception of metastatic neuroblastoma there is still
      no proven role for this treatment strategy. It is more than 10 years since this
      approach was used in neuroblastoma and it has subsequently been applied to most
      of the common childhood solid tumours. Although a single randomised study has
      suggested that the progression-free survival is significantly prolonged with high
      dose melphalan, the superiority of this over continued intensive conventional
      therapy is unclear. It seems likely that a selected subgroup of children with
      stage IV disease may benefit from megatherapy and the results of current
      randomised trials are awaited. In rhabdomyosarcoma, the duration of treatment may
      be shortened by dose escalation, but the impact on the outcome in very high-risk
      patients remains unproven. In Ewing's sarcoma, there has been difficulty defining
      high-risk patients, but recent studies suggest that megatherapy may have a role
      in patients with bone or bone marrow disease who have little chance of long-term
      survival with conventional chemotherapy approaches. In brain tumours, the results
      have been disappointing for gliomas, but there is currently enthusiasm about a
      possible role in the chemosensitive primitive neuroectodermal tumours. In this
      group of diseases which are inherently chemosensitive, the poor results from
      chemotherapy in the past have resulted from a failure to achieve appropriate drug
      levels at the tumour site and this may be potentially overcome by dose
      escalation. In Wilms' tumour, although the overall cure rate is very high, there
      appears to be a useful role for megatherapy in certain high-risk relapsed
      patients who have little chance of cure with conventional salvage therapy. There
      is an urgent need for international collaboration to design randomised studies
      which will as rapidly as possible address the issue of the role of these
      expensive and high morbidity procedures in childhood cancer.

PMID- 7626857
TI  - [Experience with other tumors: breast, ovary, brain tumors and sarcomas].
AB  - High-dose chemotherapy and autologous bone-marrow was widely tested in different
      solid tumors. This treatment is under investigation in metastatic and high-risk
      loco-regional breast cancer in France (Pegase protocol). There is few evidence of
      a role of high-dose chemotherapy in the first line treatment of poor-risk germ
      cell tumors. However the role of high-dose chemotherapy in the salvage setting of
      germ tumors is studied in an european randomized trial. At present there is no
      evidence of the role of this treatment in other solid tumors of adulthood.

PMID- 7626859
TI  - [Classification of cancers for clinical use].
AB  - The clinical classification of cancers has become necessary along the past
      decades to optimize treatments according pronostic and to allow scientific
      exchanges among the medical oncology community. The TNM staging system, with the
      derivates classifications, and the use of pronostic models, is now universal and
      applied to almost all human neoplasms. Therefore, the classification of cancers
      is now become an evoluting instrument of long-term evaluation of neoplastic
      diseases as well as medical oncology practice.

PMID- 7626858
TI  - [Relation dose efficacy in chemotherapy: the example of breast cancer].
AB  - The efficacy of cytotoxic chemotherapy when administered at conventional doses in
      breast cancer is limited and allows to understand some failures in the adjuvant,
      advanced or inflammatory and also in metastatic settings. The use of high dose
      chemotherapy is one way to try to improve its efficacy based on response rate,
      overall and disease free survival. Retrospective analysis on dose efficacy in
      breast cancer suggest that the results obtained by cytotoxic chemotherapy are
      linked to the administered dose without being able to assess this hypothesis with
      certainty. In 1995, the concept of dose efficacy remains to be validated by the
      appropriate prospective randomized trials.

PMID- 7626860
TI  - [Role of surgery in the treatment of cancer. Surgical oncology].
AB  - Surgical oncology requires an indispensable cultural and interdisciplinary
      approach of cancer. It needs a solid surgical formation combined with knowledges
      in biology, pathology, radiology, chemotherapy, and radiotherapy so oncologist
      surgeons are better able to define the limits of intervention according to the
      natural history of each type of tumors and the last modern therapeutic means.

PMID- 7626861
TI  - [Rehabilitation and social reintegration of cancer patients].
AB  - In France, social laws permit a total reimbursement of medical and pharmaceutical
      expenses for cancer patients. Income is also supplied to cancer patients by the
      National health service or the state to compensate for the absence of salary
      during a time period without being for civil servants or employees. Civil
      servants can be absent from their job without being dismissed for 5 years, at
      most, for cancer reason. For employees, or workers this time period is shorter,
      varying from one company to another according to local agreements. Several public
      organisations can help a previous cancer patient to return to work and the
      percentage of patients working again is good except for poorly qualified
      employees or workers due to the economic crisis. New laws allow cancer patients
      to be civil servants except if the disability does not fit with his job. The
      possibility of life insurance of cured patients depends on the site of cancer,
      the prognosis, the treatment sequellae and the delay between the treatment
      completion and the request.

PMID- 7626862
TI  - [Genes and enzymes involved in the metabolism of carcinogens].
AB  - Most chemical carcinogens are not by themselves reactive. They are in fact
      procarcinogens and, before becoming toxic, they must undergo some metabolic
      transformations, directed by enzymatic systems under genetic control. Because of
      this system of defence, xenobiotics undergo in vivo a more or less sophisticated
      metabolic process that usually involved at least two phases: after activation
      phase (or "functionalization"), then a conjugation phase that allows elimination
      of the processed molecule. The initial step is in most cases on oxidation by P450
      cytochroms. The conjugation step may involve a molecule of sulfate
      (sulfotransferase), of glucuronate (glucuronyltransferase) or of glutathione
      (glutathione-S-transferase). In man, large interindividual variations in the the
      expression in these enzymes have been demonstrated, probably depending on a
      genetic polymorphism. They are responsible for variations in individual
      susceptibility to carcinogens.

PMID- 7626864
TI  - Competency based training.
AB  - The Level 3 Operating Department Practice Award within Health Care, which is a
      National Vocational Qualification (NVQ), has been available since 1991. It is
      open to all personnel who wish to practise as the equivalent of assistants to the
      anaesthetist and/or surgeon or who wish to work in the recovery area. It has
      replaced the City and Guilds of London Institute (CGLI) 752 qualification but in
      no way disadvantages those who already hold the latter qualification or ENB
      theatre certificates. The NVQ involves competence based training because the
      greater emphasis is placed on the practical skills of the student. As the
      standards are demanding this means that holders of the NVQ are well able to
      complete and perform all the tasks necessary to be effective in their jobs and,
      in addition, have the necessary background knowledge and understanding to produce
      a safe practitioner. Since the introduction of the ODP/NVQ, theatre managers and
      their staff have been able to observe its progress, some with interest and,
      regrettably, some with cynicism.

PMID- 7626863
TI  - [Role of retroviruses in human cancerogenesis].
AB  - Retroviruses are viral agents which are natural and experimental inductors of
      leukemias and solid tumors among numerous animal species. In man, they are
      implicated as ethiological agents of a specific type of leukemia, adult-T cell
      leukemia. Thus is for retrovirus HTLV-I. Another retrovirus, HIV, implicated in
      AIDS is capable of leading to the formation of several types of opportunistic
      tumors, such as non Hodgkin lymphomas and Kaposi's sarcoma.

PMID- 7626865
TI  - Laparoscopic training for theatre personnel.
AB  - Many theatre units have begun to liaise with surgeons and with manufacturers to
      train theatre personnel to work as part of a team carrying out laparoscopic
      surgery. Indeed, some courses are already well established. This short article
      describes the experience of one theatre unit of such a training programme.

PMID- 7626866
TI  - African diary.

PMID- 7626867
TI  - The tunable dye laser--introducing new technology into the working environment.
AB  - As we are all aware, the pace of change in all aspects of specialised critical
      care is constant, and finding time to understand and incorporate new
      technological advances into our nursing practice is not easy. Theatre nursing is
      demanding enough with the increasing demand for theatre sessions, staff shortages
      and financial limitations, but the obvious benefits of medical advances for
      patients easily outweigh these as this article will hopefully illustrate. We are
      all willing to embrace positive change but do feel the need to incorporate it
      safely into our practice, a dilemma recognised by Evans.

PMID- 7626868
TI  - Declining risk of reoperative valvular surgery.
AB  - One hundred eleven patients underwent their second to fifth open heart operation,
      excluding isolated coronary revascularization. The procedures included repeat,
      single and multiple valve replacements, concomitant redo valve surgery, plus
      aortic root, and/or aortic arch reconstruction with or without coronary bypass
      graft. Six patients had heart transplantation as the final procedure. The article
      is based on the analysis of the experience of one surgeon with particular
      emphasis on technical considerations and factors enhancing outcome. There were
      two deaths for an early (hospital--30 days) mortality of 1.8%. There were three
      sternal wound complications. Two patients suffered cerebrovascular accident (one
      with permanent residual deficit), and one patient required reoperation for
      tamponade. The text contains a relatively detailed description of the technical
      maneuvers applied for several different categories of procedures used.

PMID- 7626869
TI  - The CarboMedics "top hat" supraannular prosthesis in the small aortic root.
AB  - Twenty-three patients, 11 men and 12 women, with a mean age of 64 (range, 34 to
      78) underwent aortic valve replacement (AVR) with a CarboMedics "Top Hat"
      supraannular prosthesis between March 1993 and August 1994. The top hat
      supraannular prosthesis, a standard bileaflet valve with the cuff transferred to
      the valve inflow level, allowed implantation of 21-mm, 23-mm, and 25-mm valves,
      where a standard 19-mm or 21-mm valve would have usually been placed. One patient
      who had been in preoperative cardiogenic shock died in the perioperative period.
      Another had an intraoperative cerebral embolism with permanent impairment. Follow
      up on 22 of 23 patients over a mean period of 9 months revealed mean Doppler
      gradients of 18 +/- 6 mmHg, 15 +/- 2.8 mmHg, and 11 mmHg, for the 21-mm, 23-mm,
      and 25-mm valves, respectively. Functional improvement was noted, with 17
      patients in New York Heart Association (NYHA) Class I and 6 in NYHA Class II,
      postoperatively, compared with 0 in Class I, 9 in Class II, 10 in Class III, and
      4 in Class IV, preoperatively. One patient showed reduced postoperative
      ventricular function with fractional shortening below 25%. Pandiastolic
      regurgitation intrinsic to the valve graded as slight was noted in all patients.
      Other postoperative complications included one patient with anticoagulant-related
      gastrointestinal bleeding and one other with prosthetic valve endocarditis
      successfully treated with antibiotics. The CarboMedics top hat valve allows a
      gain in prosthesis size of 2 mm to 4 mm in the aortic position over standard
      prostheses, resulting in favorable postoperative hemodynamics.

PMID- 7626870
TI  - Stentless porcine bioprostheses in the treatment of aortic valve infective
      endocarditis.
AB  - Between January 1992 and June 1994, 23 patients underwent surgery for aortic
      valve endocarditis at the Department of Cardiovascular Surgery of the University
      of Verona; a subgroup of 10 patients underwent aortic valve replacement with a
      porcine stentless valve (Biocor LTDA n = 8; Toronto SPV n = 2). There were 7
      males and 3 females with a mean age of 56.3 years (range, 36 to 73 years). Eight
      patients had active endocarditis and two had healed endocarditis. Nine patients
      had native valve in endocarditis, the presence of a bicuspid aortic valve in 2,
      and 1 patient had recurrent prosthetic valve endocarditis (PVE), 7 of whom were
      in New York Heart Association (NYHA) Functional Class IV. The main indications
      for operation were congestive cardiac failure, active sepsis, and presence of
      large and mobile vegetations by echo and arrhythmias. There were no operative or
      late mortalities in this subgroup of patients. Short-term survival is 100% at a
      mean follow-up time of 11.2 months (range, 4 to 18 months), with no recurrent
      endocarditis or valve-related complications.

PMID- 7626871
TI  - Intraoperative angioscopy for coronary bypass surgery.
AB  - Despite advances in coronary artery surgery, technical abnormalities remain a
      significant cause of early graft closure. The development of small fiberoptic
      angioscopes now allows direct intravascular magnified examination. Seventy-five
      distal anastomoses and vein grafts, and five selected coronary arteries were
      examined with 0.8- to 2.5-mm diameter angioscopes introduced through the proximal
      vein graft while irrigating with clear cardioplegia. Angioscopic findings were
      correlated with angiographic data, vessel morphology, graft flow, and
      postoperative course. Satisfactory images were obtained in 72 of 75 anastomotic
      inspections. Each examination took less than 2 minutes and required less than 100
      cc of flush. Angioscopic abnormalities that did not require revision were noted
      in 17 of 72 anastomoses; intimal flaps in 9, thrombus on posterior wall plaque in
      4, intimal irregularities in 4, bucking of posterior wall in 3, and valve near
      anastomoses in 1. No outflow obstruction nor misplaced sutures were noted.
      Average flow rate through the grafts with anastomotic angioscopic abnormalities
      was 33 cc/min versus 40 cc/min in the remaining grafts. However, regression
      analysis revealed that low-graft flow was correlated with vessel size and runoff
      but was not with angioscopic findings. Intracoronary angioscopy revealed
      discrepancy with angiographic findings in 4 of the 5 examinations. No
      complications occurred as a result of angioscopy. No graft closure has occurred
      during early follow-up. Intraoperative angioscopy can be done with minimal
      alteration of the usual routine. The 24% occurrence of minor angioscopic
      abnormalities did not appear to compromise graft flow or early patency.

PMID- 7626872
TI  - Warm heart surgery: a prospective comparison between normothermic and tepid
      temperature.
AB  - Due to concerns about complications from normothermic core temperature during
      cardiopulmonary bypass, we initiated a prospective randomized study of 200
      consecutive patients. In one group (group A), both the heart and the body
      temperature were kept at 37 degree C. In the second group (group B), both the
      body and myocardial temperature were allowed to drift down to 34 degree C. There
      were no differences between these two groups in age, sex, preoperative numbers of
      elective, urgent, emergent, redo patients, or coronary artery bypass (CAB),
      valve, CAB/valve procedures. Their preoperative neurological, pulmonary, renal,
      and vascular disease status were similar. Preoperative EF was 53% in group A (100
      patients) and 52.5% in group B (100 patients). Group A required more volume (p =
      0.001) and had less urine output (p = 0.03) during and post bypass. Group A
      required more phenylephrine hydrochloride (p = 0.05) and had more difficulty
      managing blood pressure. Strokes and renal failure necessitating dialysis
      occurred more often in group A but without statistical significance. More
      difficulties occurred in the normothermic (37 degrees C) group and
      cardioprotective effects of warm heart surgery may remain intact at 34 degrees C.
      Mild "drifted/tepid" hypothermic heart surgery could be a better and safer
      procedure.

PMID- 7626874
TI  - Transesophageal echocardiography in cardiac surgical emergencies.
AB  - The value and utility of transesophageal echocardiography (TEE) in unstable
      cardiac surgical patients have been assessed; 119 TEE studies were performed and
      evaluated in the emergency setting. The studies were performed in the cardiac
      surgical intensive care unit (n = 62) and in the operating room (n = 57). There
      were 81 men and 38 women with a mean age of 58.2 years. The indications for TEE
      were as follows: hypotension refractory to conventional treatment (n = 83);
      prosthetic or native valve dysfunction (n = 25); and suspected aortic dissection
      (n = 10). TEE provided valuable diagnostic information in 107 patients and was
      completely normal in 12 patients. Based on these results 22 patients had urgent
      surgical intervention without further studies. The average time to diagnosis was
      11.2 minutes. No significant complications were noted. Our results suggest that
      TEE is highly diagnostic for most of the abnormalities responsible for
      hemodynamic instability in the perioperative period and facilitates decision
      making in cardiac surgical emergencies.

PMID- 7626873
TI  - The effect of multiple blood conservation techniques on donor blood exposure in
      adult coronary and valve surgery performed with a membrane oxygenator: a
      multivariate analysis on 1310 patients.
AB  - The object of the study was to retrospectively evaluate protective and risk
      factors for receiving donor blood products and red cell transfusions after
      coronary and valve surgery performed with a hollow-fiber oxygenator and with
      multiple blood-saving techniques. During the period of January 1991 to June 1993,
      1310 patients underwent primary coronary and valve surgery using a hollow-fiber
      oxygenator at our institution; the mean age of this population was 61 +/- 10
      years; 977 patients were men (74.6%). Of these patients, 73.5% (963/1310)
      underwent coronary, 21.5% (281/1310) valve, and 5% (66/1310) combined surgery.
      Two hundred seventy-six (21.1%) needed donor blood product transfusions, while
      153 (11.7%) patients underwent red cell transfusions. Significant risk factors
      for homologous blood product exposure after multivariate logistic regression
      analysis were, in order of importance: (1) postoperative blood loss (O.R. =
      1.0009 per mL, p = 0.0000); (2) cardiopulmonary bypass (CPB) time (O.R. = 1.008
      per min, p = 0.0001); (3) age at intervention (O.R. = 1.031 per calendar year, p
      = 0.0026); and (4) reoperation for bleeding (O.R. = 1.71, p = 0.0078). Protective
      factors were: (1) male gender (O.R. = 0.56, p = 0.0000); (2) preoperative
      withdrawal of autologous blood (O.R. = 0.66, p = 0.0018); and (3) a preoperative
      hematocrit greater than 34% (O.R. = 0.76, p = 0.0005).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7626875
TI  - Endothelial lined skeletal muscle ventricles: open and percutaneous seeding
      techniques.
AB  - Twelve bilateral skeletal muscle ventricles (SMVs) were constructed in six dogs
      by wrapping each latissimus dorsi muscle around a cylindrical, plastic mandrel
      (volume 30 cc). After 6 to 10 weeks, five dogs had one of their SMVs seeded with
      allogeneic cultured canine endothelial cells (8 x 10(6) cells/pouch) via an open
      technique, whil the contralateral SMV was seeded by percutaneous injection of
      cells into the space around the mandrel. After 1 week, the SMVs were excised.
      Viable, adherent endothelial cells were present in all seeded pouches; this was
      confirmed via fluorescent microscopy with several endothelial cell markers; KLH
      2, dilacetylated low-density lipoprotein and antibodies to von Willebrand factor.
      The inner lining of the SMVs were also examined with scanning and transmission
      electron microscopy; the highest concentration of cells were seen at the apex
      where a continuous endothelial monolayer was observed. No significant difference
      in the distribution or the morphology of the endothelial lining was noted between
      the open and percutaneous seeding techniques. These data show that SMVs can be
      seeded with an endothelial monolayer using both open and percutaneous techniques.

PMID- 7626876
TI  - Warm heart surgery eliminates diaphragmatic paralysis.
AB  - Since January 1992, we adopted a new method of myocardial protection: warm blood
      cardioplegia with continuous ante-retrograde combined delivery during
      normothermic cardiopulmonary bypass, (CPB) instead of cold blood intermittent
      cardioplegia plus topical ice slush in hypothermic CPB. We have compared
      postoperative chest X-rays of 50 patients who underwent elective coronary artery
      bypass with normothermic CPB to postoperative chest X-rays, of 50 patients
      operated upon with hypothermia. In the cold group transitory diaphragmatic
      paralysis, as well as pleural effusions and thoracentesis related to the
      hypothermia, and topical cooling, were statistically increased over that of warm
      group. The data suggest that topical cooling with slush ice is responsible for
      phrenic nerve injury and that warm heart surgery has no associated incidence of
      diaphragmatic injury.

PMID- 7626877
TI  - The use of 25% glutaraldehyde solution to strengthen the aorta of patients with
      annuloaortic ectasia, ascending and aortic arch aneurysms.
AB  - Aortic friability is a problem of great concern and frustration for those
      performing operations on patients with ascending and arch aortic aneurysms, and
      particularly, on patients with annuloaortic ectasia. We have used 25%
      glutaraldehyde to successfully strengthen the distal aorta of three such
      patients. After the application, the aorta wall held sutures without tearing.
      Postoperative bleeding was minimal in each case. No neurological events were
      noticed, and all of the patients were discharged home within 2 weeks. The
      application of this tanning solution to such a friable aortic tissue should be
      considered as a helpful alternative to reduce postoperative bleeding, which is
      the most common complication after this type of surgery.

PMID- 7626878
TI  - Surgical treatment of transposition of great arteries with interrupted pulmonary
      artery: a rare association of embryopathies.
AB  - The first case of TGA with VSD, ASD, and interrupted LPA and its successful
      surgical treatment is being reported along with a review of the relevant
      literature. The dominant presenting clinical features have been explained and an
      attempt has been made to explain the paucity of records in regard to this
      embryopathy. An arterial switch for TGA and a glutaraldehyde pretreated
      autologous pericardial roll for repair of interrupted LPA were carried out. Pre-
      and postoperative hemodynamics and angiography data are also presented.

PMID- 7626880
TI  - Partial helical sternotomy to promote enhanced sternal stability.

PMID- 7626879
TI  - Blood anesthesia for cardiopulmonary bypass.
AB  - Cardiopulmonary bypass (CPB) causes bleeding and thrombotic complications, fluid
      retention and temporary dysfunction of every organ system. This morbidity of CPB
      is primarily do to activation of blood proteins and cells by contact with
      nonendothelial cell surfaces of the wound and biomaterials of the extracorporeal
      perfusion circuit. CPB is not possible without heparin, yet heparin is not an
      ideal anticoagulant and does not prevent activation of at least five plasma
      protein systems and five blood cells. Stimulation of these blood elements
      produces over 25 vasoactive substances that alter vascular tone, capillary
      permeability, and cardiac myocyte contractility. In addition, CPB produces
      showers of microemboli that pass filters to obstruct arterioles and
      precapillaries to produce necrosis of widely dispersed, small groups of cells.
      Attempts to develop nonthrombogenic synthetic materials have failed; only the
      endothelial cell is nonthrombogenic and achieves this property by active
      metabolic processes. Although some biomaterials are less thrombogenic than
      others, all activate blood elements to initiate clotting and the body's defense
      reaction. The concept of "blood anesthesia" envisions the use of reversible
      inhibitors of key blood reactions to temporarily prevent activation of blood
      elements during CPB. If the initial reactions of blood with nonendothelial
      surfaces are blocked, production of many vasoactive substances and microemboli by
      CPB is suppressed. This conserves blood elements that are normally consumed
      during CPB and makes them available after the inhibitor is reversed. Effective,
      reversible inhibitors of platelets are entering clinical trials; reversible
      inhibitors of other key blood relations are being developed and tested at a rapid
      rate.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7626881
TI  - Meiotic drive in female mice: an essay.

PMID- 7626882
TI  - YAC/P1 contigs defining the location of 56 microsatellite markers and several
      genes across a 3.4-cM interval on mouse chromosome 11.
AB  - The characterization of three YAC/P1 contigs from adjacent segments of the
      central region of mouse Chromosome (Chr) 11 is described. These contigs are based
      upon 63 YACs and 40 P1 recombinants. From these clones, 185 end sequences were
      obtained, of which 147 sequences could be converted into sequence-tagged sites
      and mapped within the three contigs. Deletions were detected in 16 out of 63
      YACs; 19 of 63 YACs were found to be chimeric. No such aberrations were found in
      P1 recombinants. A total of 22 public and 34 newly developed microsatellite
      markers were unambiguously localized to and ordered in the contigs. In the
      cryb1/Nf1 interval of the central contig, several new genes have been identified
      by exon trapping and precisely localized with respect to known STS markers.

PMID- 7626883
TI  - The tropomodulin (Tmod) gene maps to chromosome 4, closely linked to Mup1.

PMID- 7626884
TI  - Sixty-nine kilobases of contiguous human genomic sequence containing the alpha
      galactosidase A and Bruton's tyrosine kinase loci.
AB  - Several disease loci have been mapped to the Xq21.3-Xq22 region of the human X
      Chromosome (Chr) including X-linked agammaglobulinemia (XLA), Fabry disease,
      Alport syndrome, and Pelizaeus Merzbacher disease. Upon cloning of the XLA gene,
      Bruton's tyrosine kinase (btk), both Fabry disease and XLA were mapped within the
      same 50- to 70-kb interval. In order to investigate the genomic organization of
      the region surrounding btk and the Fabry disease gene, alpha-galactosidase A
      (gla), we constructed a 6-cosmid contig spanning the region from 5' of gla to 3'
      of btk. Two of these cosmids spanning most of the coding sequence and the
      upstream region of btk and gla, U237D10 and U230D1, were sequenced by a random
      shotgun strategy combined with automated sequencing, resulting in 69 kb of
      contiguous genomic sequence. Sequencing of U237D10 showed btk to be comprised of
      19 exons spanning over 35 kb. Sequencing of U230D1 showed that the 3' end of gla
      is 9 kb from the 5' end of btk and also demonstrated the presence of two
      additional genes in the region immediately 5' to btk. The surprisingly high gene
      density is similar to that seen previously only in the human major
      histocompatibility locus.

PMID- 7626885
TI  - Alu-PCR combined with non-Alu primers reveals multiple polymorphic loci.
AB  - A marker suitable for genetic mapping and genomic fingerprinting is characterized
      by high polymorphic information content (PIC) and high "multiplex ratio" (defined
      as the number of loci that can be simultaneously typed). Towards this goal, we
      combined an Alu-specific with a non-Alu primer in a single PCR amplification
      targeting genomic regions where length polymorphisms are abundant. Three loci
      were revealed with the variable number of (AAT), (TAAA), (AG), and/or (AAAGG)
      motifs, and PIC values between 0.7 and > 0.94. Their location on Chromosomes
      (Chrs) 19q12, 17q12-q24, and 5q31.2-33.3 was determined by multipoint analysis
      with markers from CEPH database. The most common genotype for this three-locus
      marker, estimated from the occurrence of the most frequent alleles, is of the
      order of 2 x 10(-4), while the combined PIC value of a single typing experiment
      is 2.37. The use of a similar primer pair, as well as examples from the
      literature, indicates the general nature of this approach when a non-Alu
      oligonucleotide, presumably with "random" priming sites downstream of Alu
      repeats, is combined with an Alu-specific one. Clustering of DNA length variants
      in the regions adjacent to interspersed repeats provides opportunity to develop
      other highly informative multiple-locus markers similar to that described here.

PMID- 7626887
TI  - Exclusion of three candidate genes, Grpr, Cxn33, and Pdha1, for the X-linked
      cataract gene on the distal region of the mouse chromosome X.

PMID- 7626886
TI  - The bovine interleukin-4 gene: genomic organization, localization, and evolution.
AB  - Interleukin-4 (IL4) is involved in the immune response to certain parasites and
      possibly in the development of some atopic diseases since it triggers the T
      helper 2 lymphocyte response. Therefore, IL4 is a candidate gene, for example,
      for disease association studies and gene mapping. We isolated bovine IL4 cosmids
      and determined the genomic organization. Fragments carrying the exons as well as
      725 base pairs (bp) from the 5' flanking and 190 bp from the 3' flanking region
      were cloned and sequenced. The first 481 base pairs of the 5' flanking region,
      including the putative promoter sequences, are surprisingly similar (92%) between
      cattle and human. In addition, we cloned and sequenced a mixed [(t/g)a]m(ca)n
      repeat located approximately 35 kilobases upstream from the IL4 gene. It showed
      seven repeat length alleles in a limited number of animals. The IL4 gene has been
      assigned to 7q15-q21 by fluorescence in situ hybridization in cattle.
      Evolutionary aspects are discussed on the basis of sequence data as well as
      interspecies chromosomal homologies.

PMID- 7626889
TI  - The genes coding for alpha and beta catenin (Catna1 and Catnb) and plakoglobin
      (Jup) map to mouse chromosomes 18, 9, and 11, respectively.

PMID- 7626888
TI  - Distribution of the p53 pseudogene among mouse species and subspecies.

PMID- 7626890
TI  - Localization of mouse lumican (keratan sulfate proteoglycan) to distal chromosome
      10.

PMID- 7626891
TI  - Mapping of jvs (juvenile visceral steatosis) gene, which causes systemic
      carnitine deficiency in mice, on chromosome 11.

PMID- 7626893
TI  - An RFLP map of the baboon platelet-derived growth factor receptor gene.

PMID- 7626894
TI  - Mutation rates at porcine microsatellite loci.

PMID- 7626892
TI  - The rat T-cell lymphopenia resistance gene (Lyp) maps between D4Mit6 and Npy on
      RN04.

PMID- 7626895
TI  - Genetic mapping of the T lymphocyte-specific transcription factor 7 gene on mouse
      chromosome 11.

PMID- 7626896
TI  - Genetic mapping of the tumor-associated mucin 1 gene on mouse chromosome 3.

PMID- 7626897
TI  - Interspecies fluorescence in situ hybridization further defines synteny homology
      between mouse chromosome 11 and human chromosome 17.

PMID- 7626898
TI  - The skeleton in the hospital closet--20 years later: malnutrition in patients
      with GI disease, cancer and AIDS. Proceedings a conference. Los Angeles,
      California, October 1-2, 1994.

PMID- 7626899
TI  - Skeleton in the hospital closet--then and now.

PMID- 7626900
TI  - What is malnutrition? Does it matter?

PMID- 7626901
TI  - Nutritional assessment in clinical practice.

PMID- 7626902
TI  - Identification of indicators for improving the diagnosis of malnutrition.

PMID- 7626903
TI  - Relationship of nutritional markers to length of hospital stay.

PMID- 7626904
TI  - Interpretation of clinical studies in relation to malnutrition.

PMID- 7626905
TI  - Ethics and nutritional support.

PMID- 7626906
TI  - Impact of nutritional state on quality of life in surgical patients.

PMID- 7626907
TI  - Impact of sip therapy on postoperative surgical outcome.

PMID- 7626908
TI  - Outcome of nutrition therapies in the intensive care unit.

PMID- 7626909
TI  - Specific nutrients and the immune response.

PMID- 7626910
TI  - Influence of nutrition support on clinical outcome in short bowel syndrome and
      inflammatory bowel disease.

PMID- 7626911
TI  - Clinical study of an enteral branched-chain amino acid solution in decompensated
      liver cirrhosis with hepatic encephalopathy.

PMID- 7626912
TI  - Malnutrition among geriatric patients admitted to medical and surgical services
      in a tertiary care hospital: frequency, recognition, and associated disposition
      and reimbursement outcomes.

PMID- 7626913
TI  - Nutritional intervention in the course of HIV disease.

PMID- 7626915
TI  - The lack of bronchodilator effect and the short-term safety of cumulative single
      doses of an inhaled potassium channel opener (bimakalim) in adult patients with
      mild to moderate bronchial asthma.
AB  - The aim of this study was to assess the bronchodilator effect and short-term
      safety of cumulative single doses of inhaled bimakalim (E Merck, Darmstadt), a
      potassium channel opener, compared to placebo in 12 adult patients with chronic,
      mild to moderate, non-allergic bronchial asthma. The study was a randomized,
      placebo-controlled, cross-over study and the only efficacy variable measured was
      the forced expiratory volume in one second (FEV1). The patients had an FEV-1 >
      50% of predicted normal value and a reversibility of more than 15% at entrance to
      the study. Inhaled bimakalim and placebo were delivered by a Pariboy nebulizer.
      The doses tested in a cumulative manner were 10, 25, 40 and 100 micrograms (total
      cumulative dose 175 micrograms), each individual dose given at 60-min intervals.
      Plasma bimakalim concentrations were measured at time 0 and 60 min after each
      dose. No bronchodilator effect was shown, with inhaled bimakalim at the doses
      tested. Reasons for the lack of efficacy of inhaled bimakalim in this study may
      be due to low doses of administered drug or to a true lack of bronchodilatation
      effect in the study patients. Inhaled bimakalim was well tolerated. No headache
      or cardiovascular events were seen with the cumulative dose of 175 micrograms
      bimakalim.

PMID- 7626914
TI  - Hypoxaemia and the renin-angiotensin system: new answers for old questions.

PMID- 7626917
TI  - Acute effects of hypoxaemia and angiotensin II in the human pulmonary vascular
      bed.
AB  - Hypoxaemia and angiotensin II both cause pulmonary vasoconstriction and co-exist
      as pathophysiological pulmonary pressor stimuli in patients with cor pulmonale.
      Evidence from animal studies, however, suggests that angiotensin II may modulate
      the hypoxic pulmonary vasoconstrictor response. We have therefore studied how
      hypoxaemia and angiotensin II interact in the human pulmonary vascular bed. Eight
      male volunteers were studied on two occasions. From baseline (T0) onwards,
      subjects breathed room air at one visit, and on the other, a nitrogen/oxygen
      mixture which rendered arterial oxygen saturation between 75% and 80%. After 30
      min (T30), angiotensin II was infused for a further 30 min (until T60). Mean
      pulmonary artery pressure (MPAP) and total pulmonary vascular resistance (PVR)
      were determined by pulsed-wave Doppler echocardiography at T0, T30 and T60. The
      change in MPAP (delta MPAP) due to hypoxaemia and angiotensin II together was
      18.0 +/- 1.3 mmHg, significantly greater than the delta MPAP response to either
      hypoxaemia alone (13.4 +/- 1.1 mmHg) or angiotensin II alone (10.3 +/- 1.1 mmHg).
      In terms of change in PVR (delta PVR), the response to hypoxaemia and angiotensin
      II together (230 +/- 25 dyne.s/cm5) was no different from the response to ANG II
      alone (214 +/- 31 dyne.s/cm5), although both these were significantly greater
      than delta PVR with hypoxaemia alone (114 +/- 12 dyne.s/cm5). The delta MPAP and
      delta PVR responses to angiotensin II were significantly greater when normoxaemic
      than when hypoxaemic: delta MPAP mean difference 5.6 mmHg (95% confidence
      interval (CI) 3.0-8.2); delta PVR mean difference 98 dyne.s/cm5 (95% CI 16-181).
      Angiotensin II therefore produced significantly less pulmonary vasoconstriction
      when hypoxaemic compared with normoxaemia.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7626916
TI  - Adrenoceptor-stimulated endothelium-dependent relaxation in porcine
      intrapulmonary arteries.
AB  - The responses of rings of isolated adult porcine intrapulmonary arteries to
      noradrenaline were observed. The effects of prazosin (alpha-1 adrenoceptor
      antagonist), yohimbine (alpha-2 adrenoceptor agonist) and N-omega-nitro-L
      arginine methyl ester (L-NAME) on the noradrenaline responses were studied. In
      addition, following contraction with prostaglandin PGF2 alpha, the responses to
      noradrenaline or UK 14304 (alpha-2 adrenoceptor agonist) were observed alone and
      in the presence of either prazosin or yohimbine. The effects of UK14304 were also
      observed following precontraction with phenylephrine. Noradrenaline produced an
      initial increase in vascular tone followed by a decrease and then a second
      increase in tone at high concentrations. The initial contractile response was
      inhibited by prazosin or yohimbine. L-NAME or endothelium removal enhanced the
      contractile responses and abolished the mid range reduction in tone. Following
      PGF2 alpha pre-contraction, UK14304 further increased the tone, with a reduction
      in tone at higher concentrations. the contractile effect was augmented by
      prazosin. Following phenylephrine pre-contraction, UK14304 only produced
      reduction in tone. In conclusion, in porcine intrapulmonary arteries, L-NAME
      inhibited noradrenaline induced endothelium dependent reduction in tone, which
      was also inhibited by alpha-1 and alpha-2 antagonists. UK14304 demonstrated
      partial alpha-1 agonism.

PMID- 7626918
TI  - Non-specific airway hyperreactivity in isolated respiratory preparations from
      guinea-pigs sensitized and challenged with ovalbumin.
AB  - Airway hyperreactivity to physical, chemical, immunological and pharmacological
      stimuli is well documented in vivo. The aim of this study was to investigate
      whether tissues taken from guinea-pigs that had been shown to display
      hyperreactivity in vivo after antigen challenge were also hyperreactive in vitro.
      Isolated airway-perfused lungs from ovalbumin-sensitized guinea-pigs challenged
      24 h beforehand with an aerosol of ovalbumin showed a significant (P < 0.05)
      increase in responsiveness to the bronchoconstrictor response to a bolus dose of
      carbachol (10 micrograms) when compared with saline challenged animals. The
      contractile responses to single doses of carbachol (10 micrograms) and histamine
      (30 micrograms) in immersed tracheal spiral preparations taken from sensitized
      animals exposed to the ovalbumin were also significantly enhanced (P < 0.05). A
      non-significant leftward shift was observed in the concentration-response curve
      for histamine in challenged perfused lungs from ovalbumin-challenged animals
      compared with an NaCl challenge. Concentration-response curves to carbachol and
      histamine in immersed tracheal spirals were virtually superimposed. Therefore,
      this study has shown non-specific airway hyperreactivity of isolated airway
      perfused lungs at 24 h following a challenge of sensitized guinea-pigs with
      aerosolized ovalbumin, although this was not evident from concentration-response
      curves in immersed trachea. The isolated perfused lung therefore provides a
      simple method for further evaluation of the mechanisms of airway hyperreactivity.

PMID- 7626919
TI  - Effects of lung surfactant factor (LSF) treatment on gas exchange and
      histopathological changes in an animal model of adult respiratory distress
      syndrome (ARDS): comparison of recombinant LSF with bovine LSF.
AB  - Repetitive lung lavage of adult rats leads to lung injury similar to ARDS
      resulting in poor gas exchange, protein leakage and infiltration of
      polymorphonuclear neutrophils (PMN) into the alveolar spaces (J Appl Physiol
      1983; 55: 131-138). In a previous dose response comparison we have demonstrated
      that poor gas exchange could be improved by lung surfactant factor (LSF)
      instillation soon after lavage. Since Surfacten (Tokyo Tanabe Co. Ltd., Tokyo,
      Japan) was described in vitro to inhibit PMN activity, we compared this
      preparation with a Recombinant LSF preparation (Byk Gulden, Konstanz, Germany;
      phospholipids plus human identical surfactant protein C) at doses of 25, 50 and
      100 mg/kg body weight. Their efficacy was compared with an untreated control
      group with respect to improving gas exchange, inhibition of hyaline membrane
      formation and inhibition of the inflammatory response after multiple lavage.
      Tracheotomized rats were pressure-controlled ventilated (Siemens Servo Ventilator
      900C, Sweden) with 100% oxygen at a respiratory rate of 30 breaths/min,
      inspiration:expiration ratio of 1:2, peak inspiratory pressure (PIP) of 28 cmH2O
      at positive end-expiratory pressure (PEEP) of 8 cmH2O. Two hours after LSF
      administration PEEP was reduced from 8 to 6 cmH2O (first PEEP-reduction), from 6
      to 3 (second reduction) and from 3 to 0 cmH2O (third reduction) and finally
      raised to 8 cmH2O. Results for the averaged partial arterial oxygen pressure
      [PaO2 (mmHg)] of the 2 h period [PaO2(5'-120')] and for the PaO2 during the
      second PEEP reduction [PaO2(PEEP23/3] were calculated. Both LSF preparations
      caused a dose-dependent increase of the PaO2 (5'-120') and the PaO2(PEEP23/3).
      Similarly, the formation of hyaline membranes was inhibited by both LSF
      preparations in a dose-dependent manner. Inhibition of the inflammatory response
      (infiltration of PMN) was not effected by either of the LSF preparations at any
      dose level. The described variations in ventilator settings are useful to
      evaluate the deflation stability and re-expansion potential of different LSF
      preparations. The reported results give evidence that prevention of atelectasis
      by LSF treatment improves gas exchange and inhibits formation of hyaline
      membranes, leading to the conclusion that LSF treatment may be a promising
      therapy in ARDS patients.

PMID- 7626921
TI  - AHNA certificate program in holistic nursing courses. AHNA certificate program in
      healing touch courses.

PMID- 7626920
TI  - Codeine-induced bronchoconstriction and putative bronchial opiate receptors in
      asthmatic subjects.
AB  - To determine whether a mu opiate agonist can constrict the human airways, the
      dose of codeine (C) or histamine (H) producing a 40% decrease (PD40) in specific
      airway conductance (SGAW) was measured in 17 asthmatic and 14 normal subjects.
      Then, the subjects were skin tested with C and H, and the effect of naloxone (N)
      and chlorpheniramine (CP) on PD40-C was assessed. In five asthmatic subjects
      responding to less than 5 mg (16.6 mumol) inhaled C, SGAW was also recorded after
      oral administration (30 mg) and pharyngeal spraying (5 mg) of C. PD40-C could be
      determined in 11 of the 17 asthmatics but in none of the normal subjects. This
      constrictor effect lasted less than 15 min, was unrelated to resting airway
      caliber, and required a relatively high bronchial sensitivity to H (PD40-H
      usually less than 0.2 mumol) and high doses of C (11.93 +/- 12.0 mumol). However,
      in C responders, PD40-C and PD40-H were unrelated. C-induced bronchoconstriction
      was blunted by N in a dose-dependent fashion and to a mild and inconsistent
      degree, by CP. Pharyngeal spraying or oral challenge with C failed to change
      SGAW. Skin sensitivity to H and C was similar in C-responders and non-responders.
      In conclusion, large doses of inhaled C constrict the airways of asthmatic
      subjects highly sensitive to H. This effect seems mediated through (mu?) opiate
      receptors located bronchially rather than centrally, pharyngeally or in the skin.
      In C-induced bronchoconstriction H liberation plays a contributory but minor
      role. Skin and bronchial sensitivity to C are unrelated.

PMID- 7626922
TI  - Charting a course for doctor-nurse collaboration.

PMID- 7626924
TI  - Just listen--then obey!!

PMID- 7626923
TI  - Nursing diagnosis & energy field disturbance.

PMID- 7626925
TI  - Delegation of school health services to unlicensed assistive personnel. A
      position paper of the National Association of State School Nurse Consultants.

PMID- 7626926
TI  - Body piercing: promoting informed decision making.
AB  - Although school nurses may be unfamiliar with adolescent body piercing, they are
      in a key position to assist students who are considering these procedures.
      Information about various types of body piercing, student experiences, and
      teaching strategies to talk with adolescents about this procedure are presented.
      Nurses can utilize the data to help students make informed decisions about body
      piercing.

PMID- 7626927
TI  - Tourette syndrome: update and review.
AB  - Tourette Syndrome is a movement disorder of childhood onset, characterized by
      multiple motor and phonic tics. In addition to tics, some children exhibit
      repetitive habits and recurring thoughts, and others may manifest problems of
      inattention, impulsiveness, and hyperactivity. Over the past two decades there
      has been increased interest in Tourette Syndrome, because it provides a useful
      model for examining the interaction of genes and environment, as well as
      neurobiology and behavior. This article provides school nurses and nurses working
      in school-based clinics with a general review of Tourette Syndrome and associated
      disorders.

PMID- 7626928
TI  - Continuous quality improvement and school nurses' problem solving methods.
AB  - The concept of continuous quality improvement is already well known in industry.
      It is, however, potentially applicable to any organization that provides products
      or services (health care and education) to customers (students and their
      families, teachers, etc.). In the present situation of increasingly complex
      health care needs of many students, continuous quality improvement--which
      involves problem solving and management techniques to effect services--is a
      relevant concept in the school setting.

PMID- 7626929
TI  - Nursing practice management: spina bifida.

PMID- 7626930
TI  - Leadership revisited.

PMID- 7626931
TI  - Delegation to assistive personnel by school nurses--one state's experience.
AB  - Budget cuts to education, reduction of school health services and an increase in
      the nursing needs of school-age children have placed pressure on school nurses to
      delegate nursing procedures to assistive personnel. This paper reports on a study
      of school nurses in a Midwestern state. Nurses reported refusing to delegate,
      delegating against their better judgment, delegating without knowledge of the
      assistant's qualifications or without providing orientation or training, and
      delegating because they were told to by someone else. The study identified
      factors considered by nurses when deciding to delegate a procedure, educational
      preparation for delegation, and problems experienced with delegation.

PMID- 7626932
TI  - Why industrial action by nurses is not justified.

PMID- 7626933
TI  - Enhancing service provision for people with learning disabilities.

PMID- 7626934
TI  - Drug therapy for patients with rheumatoid arthritis.
AB  - Many rheumatic diseases such as rheumatoid arthritis are chronic with no known
      cure. In mild rheumatic disease analgesia and non-steroidal anti-inflammatory
      drugs are often sufficient to control symptoms; however, when the disease is
      severe disease-modifying and antirheumatic drugs are prescribed which are
      potentially toxic. Nurses have an important role in the monitoring and
      administration of these drugs.

PMID- 7626935
TI  - Management of hypoglycaemia.
AB  - Hypoglycaemia is usually a side-effect of the medication for diabetes. This
      article explains the mechanisms of hypoglycaemia and the factors which may
      precipitate it. It outlines the treatment of mild, moderate and severe reactions
      and describes how hypoglycaemia can often be prevented by forward planning.

PMID- 7626936
TI  - Initiation of insulin therapy at home.

PMID- 7626937
TI  - Specialist nurses must form their own professional body.

PMID- 7626938
TI  - The development of advanced nursing practice: 1.
AB  - The PREPP report became a reality in April 1995. This article, the first of two
      parts, analyses the role of the advanced nursing practitioner and outlines some
      of the changes in nursing that have led to the need to reorganise clinical
      practice.

PMID- 7626940
TI  - The evolving role of the clinical nurse specialist.
AB  - There is still a great deal of confusion surrounding the role of specialist
      nurses. These individuals are often the most confused as to the contribution they
      can make to nursing as a continually evolving profession of the 1990s. By
      clarifying the relationship between research, theory and education, their role
      identity is enhanced.

PMID- 7626939
TI  - Competency through being: the enemy within?
AB  - Nurses are taking on more medical tasks but is this appropriate? If so, does this
      advance nursing practice? The issue hinges on the nurse's competency which is
      central to professional nursing practice.

PMID- 7626941
TI  - Parameters of wound assessment.
AB  - Close examination of all aspects of a patient's condition as well as the wound
      itself will minimise the risk of failure in wound management. Involving the
      patient and the patient's carer can secure cooperation and compliance with
      treatment and can positively influence the outcome of care.

PMID- 7626942
TI  - Role demarcation in the community: who should do the caring?

PMID- 7626943
TI  - Ethics and accountability in health visiting.
AB  - This article discusses the ethical considerations involved in population-focused
      work. Identification and selection of appropriate health promotion interventions
      are also addressed.

PMID- 7626945
TI  - Satisfying a hunger ... a personal journey of self discovery through further
      nursing education.

PMID- 7626944
TI  - Law series: 9. clinical risk modification.

PMID- 7626946
TI  - To be a winner is powerful.

PMID- 7626947
TI  - Integrating nursing research and practice: Part II-A Delphi study of nursing
      practice priorities for research-based solutions.
AB  - Reading formal research reports and developing the art of critical analysis and
      evaluation are essential skills for nurses in practice. Here is an opportunity to
      begin developing these skills as Catherine Cooney, Susan Stebbings, Margaret
      Roxburgh, Janice Mayo, Niqui Keen, Ellen Evans and Therese Meehan report a survey
      done by nurses in Northland. Feedback through letters to the editor would be
      welcomed.

PMID- 7626948
TI  - The lived experience of registered nurses involved in the withdrawal of nutrition
      and hydration in a persistent vegetative state (PVS) patient.
AB  - The purpose of this phenomenological study was to describe the experience of five
      Registered Nurses involved in the withdrawal of nutrition and hydration in a
      persistent Vegetative State (PVS) patient. Three female and two male nurses who
      had been involved in the care of a PVS patient within the last ten years were
      interviewed. The phenomenological design was used because it provided richness
      and clarity to the issues raised. Three major findings were identified as
      positive significant experiences for these nurses: support through 'talking':
      coping through 'thinking'; and, decision making being kept 'in-house' (family and
      central care giving team).

PMID- 7626949
TI  - School girl to nurse 1960's.

PMID- 7626950
TI  - Patricia Benner: exploring her writings and their relevance for the New Zealand
      nursing world.

PMID- 7626951
TI  - Consensus conference on the first year of practice.

PMID- 7626952
TI  - Exemplar.

PMID- 7626953
TI  - Exemplar.

PMID- 7626954
TI  - Challenging the myths: the lived experience of chronic leg ulcers.
AB  - Leg ulcers are a chronic condition that affects a significant number of New
      Zealanders. While the management of the ulcers themselves has received much
      attention in the nursing and medical literature, little is known about what it is
      like to live with chronic leg ulcers, and how they impact on quality of life.

PMID- 7626955
TI  - Encephalitis lethargica: lessons for contemporary neuropsychiatry.
AB  - Encephalitis lethargica (von Economo's encephalitis), pandemic from 1917 to 1926,
      opened a window on the study of behavioral consequences of infection-induced
      subcortical disorder. Widely varying acute manifestations included extrapyramidal
      disorders, myoclonus, eye movement disorders, paralyses, delirium, mood changes,
      inverted diurnal rhythms, and catatonia. Major pathological changes involved the
      substantia nigra, globus pallidus, and hypothalamus. A symptom-free recovery
      period was often followed by postencephalitic disturbances, typically
      parkinsonism in adults and conduct disorder in children. Occurrence of
      depression, mania, obsessive-compulsive disorder, and hyperactivity in post
      encephalitic patients anticipated current concepts of the role of the basal
      ganglia in mood, personality, and obsessional syndromes. Observations of deferred
      onset and "tardy" hyperkinesias presaged current theories of the pathophysiology
      of tardive dyskinesia.

PMID- 7626956
TI  - Neuroleptic malignant syndrome and malignant hyperthermia: end of a controversy?
AB  - Two primary hypotheses have been proposed to explain the pathophysiology of the
      neuroleptic malignant syndrome (NMS): 1) that NMS is produced by abrupt and
      extensive central dopamine receptor blockade by neuroleptics, particularly in
      nigrostriatal and hypothalamic pathways; and 2) that NMS, like malignant
      hyperthermia (MH), results from a preexisting defect in skeletal muscle
      metabolism that is unmasked or provoked by neuroleptic exposure. To evaluate
      these models, the authors review studies published since 1980 of the clinical
      features, epidemiology, risk factors, laboratory assessment, and relevant animal
      models of NMS and MH. Data from these studies suggest that although NMS and MH
      are clinically similar, they are pharmacologically distinct, implying that cross
      reactivity between triggering agents is unlikely to occur.

PMID- 7626957
TI  - Neuropsychiatric evaluation in an outpatient setting.
AB  - In a retrospective case review of 336 outpatients who underwent neuropsychiatric
      evaluations, patients were sorted into five groups: 1) atypical psychiatric; 2)
      atypical neurological; 3) prior psychiatric/new-onset neurological; 4) prior
      neurological/new-onset psychiatric; 5) dementia versus pseudodementia. Cluster
      analysis of 19 presenting complaints differentiated among groups. Post
      consultation changes in preconsultation diagnosis occurred frequently overall,
      with more new case finding for psychiatric than for neurological disorders. For
      example, mood disorder diagnoses increased from 7.7% to 16.1%. Overall, dementia
      was the most common postconsultation diagnosis (32.8%). The authors conclude that
      suspicion for dementia should be high in neuropsychiatric referrals and that mood
      disorders may be especially common in neuropsychiatric patients.

PMID- 7626958
TI  - A comparison of approaches to the statistical analysis of [15O]H2O PET cognitive
      activation studies.
AB  - This study compares two of the most widely used statistical techniques for
      analyzing data obtained from [15O]H2O PET studies of brain function. The Friston
      method (SPM94) and the Worsley (Montreal) method were applied to a single data
      set of 33 subjects who were studied in a paradigm designed to evaluate memory for
      word lists. Neither of these methods emerged as either strikingly different or
      strikingly preferable, although the occasional differences may be important in
      some experiments. In general, the two methods were found to produce similar
      results in identifying brain regions active during long-term memory: frontal,
      parietal, cingulate, and cerebellar. Underlying assumptions of the two methods,
      as well as their strengths and weaknesses, are discussed.

PMID- 7626959
TI  - Evoked potential evidence for right brain activity during the recall of traumatic
      memories.
AB  - Auditory probe evoked potential attenuation was measured as an index of
      hemispheric activity in 10 subjects with a history of childhood trauma and 10
      matched subjects without such history while they recalled a neutral memory and
      then a traumatic memory. There were prominent group differences in degree of
      cerebral laterality between memory tasks (P = 0.02). The trauma group had a
      significant left dominant asymmetry during the neutral memory (P = 0.02), which
      markedly shifted to the right during the unpleasant memory (P = 0.007 for degree
      of shift). Normal control subjects did not display a significant asymmetry during
      either task, nor did they show a significant shift between tasks.

PMID- 7626960
TI  - Personality correlates of [18F]dopa striatal uptake: results of positron-emission
      tomography in Parkinson's disease.
AB  - Clinicians have long associated Parkinson's disease (PD) with personality traits
      such as seriousness and industriousness. In previous studies, patients with PD
      scored lower than matched orthopedic control subjects on novelty seeking, which
      is thought to be dopamine dependent. In this pilot study, 6-[18F]fluorodopa
      ([18F]dopa) uptake in the caudate and putamen was measured by PET in 9 patients
      with PD. Patients were also rated on three personality traits thought to be
      related to central monoamine function. Uptake of [18F]dopa in the left caudate,
      but not in other areas measured, was significantly correlated with novelty
      seeking. Results suggest that the personality traits long observed in PD patients
      may be partially mediated by striatal deficits in dopamine.

PMID- 7626961
TI  - Cerebral metabolic change in patients with AIDS: report of a six-month follow-up
      using positron-emission tomography.
AB  - The authors examined change in cerebral metabolic function over time by using PET
      in HIV-infected individuals diagnosed with AIDS. Ten subjects with AIDS received
      [18F]2-fluoro-2-deoxy-D-glucose PET scans and completed a comprehensive
      neuropsychological battery. The scan and test battery were repeated after 6
      months. Over time, the subjects showed increased relative basal ganglia
      metabolism as well as increased parietal lobe metabolism. There were no
      statistically significant changes in neuropsychological performance. These
      results suggest that PET may be more sensitive than traditional
      neuropsychological evaluation to subtle central nervous system changes in AIDS.

PMID- 7626962
TI  - Cortical perfusion and gray matter weight in frontal lobe dementia.
AB  - To evaluate the pathophysiology of frontal lobe dementia (FLD), the authors
      compared regional cerebral blood flow (rCBF) in matched groups of FLD, probable
      Alzheimer's disease (AD), and major depression patients and normal control
      subjects (n = 7 each). The planar xenon-133 technique allowed full quantification
      of cortical perfusion and estimates of the relative weight of gray matter (wg).
      FLD patients showed lower blood flow and wg in the frontal cortex than the other
      groups. Mean cortical perfusion was correlated with cortical wg in the FLD group
      only. These findings 1) suggest that matched reductions of frontal gray matter
      weight and perfusion occur in FLD and 2) support the use of rCBF in
      distinguishing FLD from AD and severe depression.

PMID- 7626963
TI  - Visual fixation and smooth pursuit eye movement abnormalities in patients with
      schizophrenia and their relatives.
AB  - Increasing evidence suggests that smooth pursuit eye movement (SPEM) dysfunction
      may serve as an endophenotype or genetic marker of schizophrenia. The authors
      tested SPEM and visual fixation (VF) in 31 patients with schizophrenia, 33 of
      their first-degree relatives, and 24 patients with major depressive disorder. A
      high rate of abnormal VF was found in schizophrenic patients and their first
      degree relatives, but not in affective disorder patients with or without
      psychotic features. Rate of VF abnormality distinguished schizophrenic patients
      from acutely depressed mood disorder patients; SPEM did not. VF and SPEM
      performance correlated only moderately, suggesting that the pathophysiologies of
      these two eye movement abnormalities may be partially independent. Implications
      for identifying a schizophrenia endophenotype are discussed.

PMID- 7626964
TI  - Memory functions in geriatric chronic schizophrenic patients: a
      neuropsychological study.
AB  - This study characterized memory functions in geriatric schizophrenic inpatients
      with a battery of memory tests sensitive to neuropsychological impairments in
      either temporal or frontal brain regions. In patients clinically rated as
      cognitively impaired (n = 24), nearly all of these measures showed deficits
      relative to less impaired patients (n = 25). Factor analysis found consistent
      correlations between the tests and their putative cortical localization.
      Discriminant analysis suggested the pattern of impairments was not consistent
      with a generalized deficit. These results introduce the possibility, to be
      directly tested with neuropathological study, that the severe cognitive deficits
      in elderly schizophrenic patients are due to dysfunctions in either the temporal
      or frontal regions of the cerebral cortex, with the specific type of dysfunction
      varying across cases.

PMID- 7626965
TI  - An automated electronic method for quantifying spinning (circling) in children
      with autistic disorder.
AB  - This pilot study examined and quantified rotational asymmetry (the tendency to
      turn preferentially to the right or left side). An automated device was used to
      measure turning (circling) in 9 children with autism and 27 normal control
      subjects and confirmed clinical observations of stereotypical spinning behavior
      in patients with autism. This behavior was significantly preferential toward the
      left side relative to control subjects (P = 0.0009, two-tailed). Group membership
      accounted for approximately 40% of variance. Although the precise causes of
      autism are not known, these preliminary data suggest that the spinning behavior
      often seen in children with neurodevelopmental disorders can be reliably
      measured. Furthermore, spinning in autism may most often manifest as specific
      right-hemispace neglect.

PMID- 7626966
TI  - Do soft signs predict treatment outcome in obsessive-compulsive disorder?
AB  - The authors examined 21 outpatients with obsessive-compulsive disorder for five
      neurological soft signs and abnormalities on two neuropsychological tests before
      and after 10 to 12 weeks of treatment with serotonin reuptake inhibitors.
      Patients showed a mean of 1.8 soft signs. Prevalences were finger-to-finger, 10%;
      adventitious movements, 29%; mirror movements, 33%; impaired cube drawing, 33%;
      and agraphesthesia, 76%. The Stroop Color and Word Test was abnormal in 10% and
      the Controlled Oral Word Association Test was abnormal in 14% of patients.
      Neither the presence of specific soft signs, the number of signs present, nor a
      combination of signs and test abnormalities predicted a poorer response to
      pharmacological treatment. Some baseline soft signs and abnormalities disappeared
      at endpoint in medication responders and nonresponders; no clear pattern of
      change emerged.

PMID- 7626967
TI  - Neuroleptic-induced respiratory dyskinesia.
AB  - Respiratory dyskinesia is a common but under-recognized side effect of chronic
      neuroleptic administration. It manifests as irregular respiration, dyspnea,
      grunting or gasping, and abnormal chest or esophageal movements. It occurs almost
      exclusively in association with other tardive effects of neuroleptics, such as
      tardive dyskinesia and tardive akathisia. Complications of the disorder include
      respiratory alkalosis and aspiration pneumonia. The authors describe 5 patients
      with respiratory dyskinesia whose cases highlight the important clinical features
      of neuroleptic-induced respiratory dyskinesia and the manner in which some cases
      may be misdiagnosed. They also review the literature on this syndrome and discuss
      the likely pathophysiological mechanisms.

PMID- 7626968
TI  - Outcome after the psychosurgical operation of stereotactic subcaudate tractotomy,
      1979-1991.
AB  - The outcome of all psychosurgical operations (stereotactic subcaudate
      tractotomies) performed at the Geoffrey Knight National Unit for Affective
      Disorders in London since 1979 is reviewed. Of patients who had suffered severe
      mood or obsessive-compulsive disorders before surgery, 84 of 249 (34%) were well
      1 year after. The effects of gender, psychiatric diagnosis, and age on outcome
      are assessed. The findings are compared with a 1975 outcome study, and
      explanations for apparent differences are proposed.

PMID- 7626969
TI  - Psychiatric manifestations of temporal lobe epilepsy in older adults.
AB  - Temporal lobe epilepsy may present with features similar to those of psychiatric
      disorders, making diagnosis difficult, especially in an elderly population. The
      authors present two cases illustrating key points leading to proper diagnosis and
      treatment.

PMID- 7626970
TI  - Sporadic encephalitis lethargica: a case treated successfully with ECT.
AB  - A patient who presented with seizures, opisthotonos, catatonia, and autonomic
      dysfunction developed features consistent with sporadic encephalitis lethargica.
      She received a course of ECT and had full recovery.

PMID- 7626971
TI  - The dementia of Gerstmann-Straussler-Scheinker syndrome: clinical variability
      demonstrated by two case reports.
AB  - Two cases of Gerstmann-Straussler-Scheinker syndrome (GSS) are discussed in
      detail. These cases illustrate the variable clinical course and mostly cortical
      features of GSS-associated dementia. Given the availability of genetic tests that
      can now diagnose GSS, clinicians should consider these tests in cases where
      patients with dementia have extensive family histories or if the clinical course
      is atypical for Alzheimer's or vascular dementia.

PMID- 7626972
TI  - General paralysis of the insane: neuropsychiatry's first challenge.

PMID- 7626973
TI  - Physiology of arousal: Moruzzi and Magoun's ascending reticular activating
      system.

PMID- 7626974
TI  - Brain stem reticular formation and activation of the EEG. 1949.

PMID- 7626975
TI  - Temporal lobe involvement in panic disorder: results of a replication study.

PMID- 7626976
TI  - The ABCs of neuropsychiatry.

PMID- 7626977
TI  - [E. M. Tareev (the centennial of his birthday)].

PMID- 7626978
TI  - [Hypertension, diabetes mellitus, atherosclerosis: clinical manifestations of
      metabolic syndrome X. Prospects of pharmacological treatment].
AB  - Currently available data and clinical observations which suggest that there is a
      pathogenetic relationship between hypertension, diabetes mellitus, and
      atherosclerosis have provided a concept of the X syndrome, by which hypertensive
      patients, mainly males, have impaired insulin tolerance along with
      hyperinsulinemia and concurrent atherogenic disorders of lipid metabolism. The
      paper discussed the specific pathogenetic mechanisms, clinical manifestations,
      and prospects for drug correction of the metabolic syndrome. The treatment of
      arterial hypertension with the calcium antagonist Lomir has indicated there are
      no negative changes as a control of non-insulin-dependent diabetes mellitus in
      the presence of effective correction of arterial hypertension and atherogenic
      dyslipidemias. With the monotherapy of essential hypertension concurrent with
      hypercholesterolemia with the alpha 1-adrenoblocker Doxazosin, in addition to the
      agent's high antihypertensive effects, the authors noted its favourable action on
      lipid spectral parameters and platelet functional activity. There is abundant
      evidence for the use of specific hypolipidemic agents in patients with essential
      hypertensive refractory to current antihypertensive drugs. The data obtained with
      the use of Lescol (fluvastatin) in patients with hypertensive disease and
      hypercholesterolemia suggest that by substantially reducing the levels of total
      cholesterol, triglycerides, low density lipoprotein cholesterol and its transport
      protein apo B does not deteriorate the quality of correction of arterial
      hypertension in this group of patients.

PMID- 7626979
TI  - [Several mechanisms of immunological adaptation in the etiology of subacute
      infectious endocarditis].
AB  - The paper deals with the possibility of identifying the persons predisposed to
      the development of subacute septic endocarditis (SSE), with the prediction of the
      course of the disease and the clarification of reasons for the inefficiency of
      antibacterial therapy. The studies performed revealed the impairment of
      cooperative interaction of the immune system, which prevents it from fulfilling
      its main task, i.e. to make an immunological surveillance over the maintenance of
      internal constancy. Imperfection of this function in SSE patients and rheumatic
      heart diseases is based on the body's sharply limited adaptation which results
      from the genetically determined low values of the immune functional reserve
      realizable by the level of intracellular energy processes which are substantially
      lower in SSE patients, as evidenced by the studies conducted. This is very
      important for predicting whether it may develop in some patients with rheumatic
      diseases. The necessity of using large doses of antibiotics decreases the
      activity of intracellular processes to a greater extent, aggravating primarily
      phagocytic function, as reflected in the efficiency of antibiotic therapy.

PMID- 7626981
TI  - [Research and practical activities of physicians at the fronts during the Great
      Patriotic War, 1941-1945].

PMID- 7626980
TI  - [Intercellular interactions in morphogenesis of initial lesions and sclerosis in
      interstitial lung diseases].
AB  - A total of 117 patients with pulmonary interstitial diseases (PID) were examined.
      The functional activity of alveolar macrophages was assayed in the lavage fluid
      and in lung tissue biopsy specimens from the generation of active oxygen forms,
      the secretion of tumor necrosis factor, fibronectin, expression of c-fos- and c
      sis-oncoprotein. The stereotypic value for various PID was the development of
      alveolitis running in 2 stages: 1) early one, including exudative inflammation
      and 2) late one, involving sclerotic changes up to the formation of the honeycomb
      lung. This results in the block of the blood-air barrier and progression of
      respiratory failure and hypoxia in patients. The morphogenesis of fibrosing
      alveolitis is formed of alveolar septal damages caused by etiological agents of
      various nature, which is frequently unclear, by active forms of oxygen, lipid
      peroxidation products, proteases, tumor necrosis factor, which are produced by
      activated alveolar macrophages and polymorphonuclear leukocytes. The alveolar
      macrophage that secretes growth factors, c-fos- and c-sis-oncoproteins plays the
      key role in the progression of sclerotic changes. Lung cancer may develop at the
      end of fibrosing alveolitis at the stage of the honeycomb lung.

PMID- 7626982
TI  - [Endothelial relaxation factor in the development of diabetic nephropathy].
AB  - Progression of diabetic nephropathy is now associated with intrarenal hemodynamic
      disorders (renal hyperperfusion, hyperfiltration, intraglomerular hypertension).
      The cause of these disorders is unclear. It is supposed that the relaxation
      factor which is produced by the vascular endothelium (endothelial relaxation
      factor-ERF) and an endogenous nitrogen oxide (NO) can cause the above intrarenal
      hemodynamic alterations in diabetes mellitus. The production of ERF/NO in 35
      patients with insulin-dependent diabetes mellitus who had varying severities of
      diabetic nephropathies were examined. These included the following groups: 1)
      patients without diabetic nephropathy (n = 9); 2) those with incipient diabetes
      mellitus (n = 12), 3) those with severe diabetes mellitus (n = 14). From groups 1
      and 2, 5 patients with hyperfiltration were identified, their glomerular
      filtration rate were more than 140 ml/ml. The ability of the cells to produce
      ERF/NO was indirectly estimated, by determining the levels of human platelet
      guanylate cyclase in the presence of L-arginine, a NO precursor, the accumulation
      of cGMP in the cells and plasma. When L-arginine was present, the activity of
      guanylate cyclase was virtually unchanged in Group 1, but it was substantially
      increased in Groups 2 and 3, by reaching its peak in patients with
      hyperfiltration (Group 4). The platelet and plasma levels of cGMP corresponded to
      the enhancement of guanylate cyclase activity in the presence of L-arginine and
      increased as diabetic nephropathy progressed. Thus, it is suggested that there is
      ERF/NO hyperproduction in patients at a high risk for diabetic nephropathy (those
      having hyperfiltration). ERF/NO is likely to promote the dilation of glomerular
      arterioles, which results in the development of hyperfiltration and
      intraglomerular hypertension, causing diabetic nephropathy progression.

PMID- 7626983
TI  - [Clinical and pathogenetic aspects of kidney damage associated with neutrophilic
      cytoplasm antibodies].
AB  - A retrospective analysis of the authors' own findings and foreign authors' data
      has demonstrated that neutrophilic cytoplasm antibodies (NCAs) play a definite
      pathogenetic role in the activation of neutrophils, a central link in the
      pathogenesis of vascular wall damage in necrotizing vasculitides. The clinical
      value of NCAs varies with their specificity. Proteinase 3 antibodies whose
      detection allows one to suppose Wegener's granulomatosis are of greater
      diagnostic value. Myeloperoxidase antibodies are revealed in various necrotizing
      vasculitides and promptly progressive glomerulonephritis and more infrequently in
      other diseases. Thus, the detection of antibodies to proteinase-3 and
      myeloperoxidase in the presence of appropriate clinical signs is most likely to
      diagnose primary necrotizing vasculitis. The changes in the levels of NCA reflect
      the activity of a renal processes and the progression of the whole disease.

PMID- 7626984
TI  - [Calcitriol: role in the regulation of erythropoiesis, use in the treatment of
      renal anemia].
AB  - The efficiency of combined therapy (erythropoietin + calcitriol) used in 8
      patients with chronic renal failure on programmed hemodialysis was comparatively
      evaluated with erythropoietin monotherapy employed in 9 patients with the same
      disease on hemodialysis which represented a control group. The anti-anemia effect
      was achieved on the average of 5 weeks earlier in the group of patients given the
      combined therapy than that in the controls. The differences between the two
      groups were statistically significant in the rate of anti-anemia effect
      achievement. Possible mechanisms by which calcitriol enhances the anti-anemia
      effect of erythropoietin, i.e. the mediated effects and direct action of
      calcitriol on erythropoiesis, are discussed in the paper.

PMID- 7626985
TI  - [New data on clinico-morphological heterogeneity of chronic glomerulonephritis].
AB  - Many years' experience in studying chronic glomerulonephritis allows the author
      to consider it to be a group entity including mesangioproliferative,
      mesangiocapillary and sclerosing (fibroplastic) types of glomerulonephritis.
      Minimal changes, focal segmental glomerular sclerosis/hyalinosis, membranous
      nephropathy which have been previously included to a group of chronic
      glomerulonephritis should be excluded since they comprise another group of non
      inflammatory glomerulopathies with primary podocytic damage. A group of
      mesangioproliferative glomerulonephritis (MPGN) is heterogeneous both in terms of
      pathogenetic parameters, on the one hand, and clinical and predictive parameters,
      on the other. Their clinical and morphological variants which differ with the
      nature of immunoglobulins in the glomerular immune complexes are presented as IgA
      , IgM-, and IgG-MPGN, each of them pretends to an individual nosological entity.
      Mesangiocapillary glomerulonephritis (MCGN) as a nosological entity showing
      specific features of morphological, pathogenetic, and clinical manifestations and
      prognosis may be left only if dense deposit diseases are deducted, which owing to
      clinical, morphological and some pathogenetic features pretends to its
      independence. The morphological types of MCGN are either types (I and III) or
      form phases (I and IV) which reflect the progression of the disease. Sclerosing
      (fibroplastic) glomerulonephritis is an evolutive form which completes both MPGN
      and MCGN. There is strong evidence for the fact that the current nephrology
      concepts of nosological entities require reconsideration on the basis of new
      research findings.

PMID- 7626986
TI  - [Disorders of intrarenal hemodynamics in glomerulopathies].
AB  - The intrarenal hemodynamics was examined in 101 patients with chronic
      glomerulonephritis (CGN) and 111 patients with type I diabetes mellitus.
      Intrarenal hypertension was diagnosed from renal functional reserve (RFR)
      depletion. In CGN intrarenal hypertension was revealed in all clinical and
      morphological variants of nephritis: in 40% of patients with a nephrotic variant,
      in 25% with a latent variant and in 83% of patients with nephritis concurrent
      with the severe urinary syndrome. In focal segmental glomerulonephritis and
      fibroplastic nephritis, the depleted RFR was encountered 4 times more frequently
      than the preserved one. There was a association between RFR and arterial
      hypertension, albuminemia, blood creatinine. In diabetes mellitus intraglomerular
      hypertension was diagnosed in 34% of patients without renal damage (those having
      normal albuminuria), in 79% at the preclinical stage of diabetic nephropathy (in
      microalbuminuria) and in 93% at its clinical stage. Intrarenal hemodynamic
      disorders in diabetes mellitus are primary and provoked by hormonal metabolic
      disorders. The morphological signs of renal hyperperfusion failure develop at the
      preclinical stage of diabetic nephropathy.

PMID- 7626987
TI  - [New approaches to the treatment of nephritis].
AB  - The paper provides evidence and results of using new therapeutical treatment of
      glomerulonephritis, such as pulse-therapy with cyclophosphane, therapy with
      angiotension-converting enzyme (ACE) inhibitors or that with antihyperlipidemic
      agents. Based on much experience with pulse-therapy with cyclophosphane (over 100
      patients with chronic glomerulonephritis (CGN) and lupus nephritis), it is
      concluded that this method is highly effective. Treating 57 patients with ACE
      inhibitors has shown that in CGN these drugs should be used only when taking into
      account their antihypertensive effect and capacity of lowering intraglomerular
      hypertension, as evidenced by the renal functional reserve, and diminishing
      proteinuria. The long-term (7-12 month) antihyperlipidemic therapy (diet and
      lovastatin) in 20 patients with CGN accompanied by the nephrotic syndrome caused
      a significant reduction in the concentration of serum cholesterol and
      proteinuria, a significant increase in serum albumin levels; remission of the
      nephrotic syndrome occurred in 9 patients; but better effects were observed in
      non-inflammatory nephropathies, such as membranous nephropathy, focal segmental
      glomerulosclerosis, and nephrosclerosis.

PMID- 7626988
TI  - [Effects of a number of cytokines on the proliferation of mesangial cells and the
      production of extracellular matrix in anti-GBM nephritis].
AB  - The interaction of IL-1 and TNF alpha in the autolous phase of anti-GBM nephritis
      was studied. The influx of mononuclear leukocytes into the glomerulus and high
      cytokine levels induced a decrease in mesangial cell proliferation and an
      increase in extracellular matrix production. The methylprednisolone suppression
      of mononuclear leukocyte infiltration caused the autocine cytokine secretion of
      mesangial cells. Cyclophosphamide decreased cytokine production, but did not
      affect mononuclear leukocyte infiltration. The absence of mononuclear leukocytes
      in the site of the injury induced by imbalance between the synthesis and
      degradation of extracellular matrix components. The uncontrolled metabolism of
      the extracellular matrix may be induced glomerulosclerosis.

PMID- 7626989
TI  - [Microbiocenotic changes in the large intestine of patients with various
      diseases].
AB  - The specific features of the components of human large bowel microbiocenosis were
      studied in healthy persons and patients with various pyo-inflammatory and other
      diseases in relation to the physiological status. The presence of a pathological
      process was demonstrated to be a powerful factor of intestinal microbiocenotic
      variations. No specific changes in the large bowel microflora were found in the
      abnormalities in question.

PMID- 7626990
TI  - [Analysis of the association of ABO blood groups and Rhesus factor with
      myasthenia].
AB  - The distribution of ABO blood groups and rhesus factor was studied in patients
      with myasthenia as compared with the control. There was a statistically
      significant association of the diseases with the rhesus-negative phenotype and
      that of generalized myasthenia concurrent with thymoma with the B (III) blood
      group. The examination revealed no other determinants of the significant
      association with the disease. The values of a disease risk were obtained for
      persons having myasthenia-associated signs. It is concluded that the Rh-negative
      phenotype shows a 1.3-fold increase in the risk of the disease as compared with
      those having Rh-positive persons.

PMID- 7626991
TI  - [Effects of nitroglycerin on myocardial contraction in patients with ischemic
      heart disease].
AB  - The effects of nitroglycerin on central hemodynamics and direct myocardial
      contractility were directly studied in 32 patients with functional class III-IV
      heart failure during aortocoronary bypass surgery. When nitroglycerin was used,
      hemodynamic parameters changed in two stages: 1) systemic blood pressure
      initially slightly increased; 2) decreases in this and other central hemodynamic
      parameters occurred. The dynamics of myocardial function was determined by its
      baseline state, dyskinetic intensity, i.e. its contractility. In patients with
      preserved myocardial function, nitroglycerin failed to cause its substantial
      dysfunction. At the same time its contractility and central hemodynamic
      parameters might considerably deteriorate in patients with moderate dyskinesia
      and furthermore with severe myocardial dysfunction.

PMID- 7626992
TI  - [Electrophysiology of the central nervous system in effective anesthesia].
AB  - In authors' opinion, the more precise methods for controlling the depth and
      efficiency of general anesthesia are those which are based on the direct control
      over the intraoperative status of the central nervous system which reflects the
      time course of the status in question. Whether monitoring of the early components
      of somatosensory evoked potentials could be used for multimodality anesthesia was
      analysed. As high as 50% or lower decreases in the amplitude of the complex N19
      P23 were typical of adequate defense, irrespective of anesthesias. The authors
      provide evidence for the efficiency of their procedure for controlling the depth
      and efficiency of general anesthesia. Some electroencephalographic phenomena of
      anesthesia were analysed with computed monitoring. The authors showed that there
      was a relative value of such signs of inadequate anesthesia as interhemispheric
      asymmetry by the leading spectral frequency and the power index of deep rhythms.
      Despite the procedure used (neuroleptic analgesia, ataralgesia, inhalation
      anesthesia, etc.), the effective anesthesia exhibited pronounced power peaks,
      otherwise there was a chaotic activity of the central nervous system. The
      physiological and clinical values of the phenomena detected are discussed in the
      paper.

PMID- 7626993
TI  - [Are the serotonin receptors life receptors?].
AB  - The paper gives evidence for the fact that serotonin and serotonin receptors are
      responsible for the occurrence of primary contractions of smooth muscles, primary
      cardiac contractions and primary brain electric activity (EEG genesis). It is
      concluded that the function of the smooth muscle, brain and heart cannot take
      place without serotonin and its receptors. This suggests that the serotonin
      receptors are life ones.

PMID- 7626995
TI  - [Steroidogenesis in patients with various adrenal and gonadal dysfunctions].
AB  - The paper deals with the results of investigations of steroidogenesis in patients
      with ACTH-dependent Icenko-Cushing's disease (CD), congenital adrenal hyperplasia
      (CAH), and stromal hyperthecosis (SH). Along with the traditional methods of
      evaluating the activity of steroid-producing glands (diurnal variations of
      steroid hormones and their precursors in the peripheral blood, their mean daily
      concentrations), the authors used a simultaneous selective catheterization
      technique for adrenal and ovarian veins. No pronounced circadian rhythms were
      revealed in most of the steroids measured in patients with CD. A sharp rise in
      the mean daily serum 17-hydroxypregnenolone concentrations coupled with the
      steady-state 17-hydroxyprogesterone level is considered to reflect the activation
      of steroid biosynthesis via the delta 5-pathway. CD patients were demonstrated to
      exhibit great differences in the daily pattern of aldosterone secretion depending
      on the development of essential hypertension. CAH patients had high 17
      hydroxypregnenolone and 17-hydroxyprogesterone levels. Like 17
      hydroxyprogesterone, 17-hydroxypregnenolone may be used as a diagnostic marker of
      CAH. Hyperandrogenism in this disorder was largely due to enhanced adrenal
      production of testosterone and delta 5 androgens DHA and DHA-S. Unlike CAH, SH
      was not associated with excessive secretion of either DHA or DHA-S, but the
      ovaries of these patients released greater amounts of testosterone, which led to
      hyperandrogenism.

PMID- 7626994
TI  - [Carnosine metabolism in excitable tissues: biological significance].
AB  - The paper provides the data characterizing the antioxidative activity of
      carnosine and its related compounds by using various complexity models wherein
      primarily various active oxygen forms are generated. Though the agent is able to
      interact with various radicals, it is more effective against a hydroxyl radical
      than homocarnosine, anserine, and acetylcarnosine. Among the compounds studied,
      acetylcarnosine and anserine provide the best protection against a superoxide
      anion, anserine is the most effective agent in suppressing the myeloperoxidase
      reaction. Homocarnosine is more effective than the other carnosine-related
      compounds, in protecting thymine from the damaging effect of ultraviolet
      irradiation. It is suggested that metabolism of these compounds makes various
      carnosine derivatives appear in relation to the tissue specificity of formation
      and conversion of active oxygen forms.

PMID- 7626996
TI  - [Morphological characteristics of the course of HIV infection in laboratory
      animals].
AB  - The integrative form of infection was obtained in cotton rats intraperitoneally
      or retrobulbarly infected with the highly-productive strain Zmb HIV-1.
      Clinically, it appeared as reduced animal weight gain and high mortality rates in
      the disease terminal stage. The proviral DNA was detected by the polymerase chain
      reaction in the genomes of cerebral and splenic cells in most animals. A
      comprehensive study of the time course of morphological changes within 6 months
      showed impairments in some CNS cells, giving rise to glial nodules and neurone
      dystrophy. It should be noted that the most profound changes were observed when
      the virus had been intraperitoneally injected. It was found that some
      pathomorphological changes were similar to those seen in human neuro-AIDS. In the
      spleen, HIV-1 first stimulated an immune response, caused an increase in the
      extent of white bulb follicles and an active formation of germinative centers,
      then involution of lymphoid formations took place.

PMID- 7626997
TI  - [Nosocomial infections in present-day traumatological-orthopedic hospitals].
AB  - Nosocomial infection remains a significant problem in modern traumatology and
      orthopedics. Staphylococcus prevails in its etiological pattern. The activation
      of microorganisms such as Acinetobacter is noted. In addition to aerobic
      microorganisms, anaerobic bacteria, nonsporulating ones, play an important
      etiological role. Anaerobic infection is seedy in 30.4% of patients' blood
      samples. Great emphasis is placed on microbial adhesiveness in the pathogenesis
      of an infectious process. The authors' investigations have shown that highly
      adhesive Staphylococci are common in severe pathological processes. The
      adhesiveness of the bacteria has been shown to depend on environmental conditions
      and the patient's status. Among the nonsporulating anaerobes there are bacteroids
      which are most highly adhesive.

PMID- 7626998
TI  - [Validity of epidemiological classification: construction of a discriminant
      criterion].
AB  - A new criterion has been proposed to assess the validity of group division
      differences obtained by preliminary cluster analysis. The method was used to
      provide evidence for the validity of differences between the groups as to
      epidemiological classifications. The paper shows it expedient to use the method
      in the epidemiological analysis.

PMID- 7626999
TI  - [The body's antioxidant system, its significance in metabolism. Clinical
      aspects].

PMID- 7627001
TI  - Profile of a Virginia Henderson fellow: Patricia A. Chamings.

PMID- 7627000
TI  - [Comparative quantitative pharmacological-EEG analysis of the effects of
      psychostimulants].
AB  - Amphetamine, caffeine, sydnocarb, meclofenoxate, adapromine, midantan, and
      nomifensine were studied for their effects on bioelectrical activity and Fourier
      EEG power spectra of the sensomotor cortex, dorsal hippocamp and lateral
      hypothalamus of freely behaving awake rats. The drop in the absolute power of all
      frequency ranges with the enhanced power of fast beta 1,2-ranges was common to
      the action of psychostimulants. In addition to the common properties, specific
      features of their action were revealed. Amphetamine, meclofenoxate, and
      nomifensine were found to increase the amplitude of the dominant peak in the
      theta-range and amphetamine shifts the frequency of the dominant peak to the
      region of faster ranges. The agents-induced electrophysiological changes
      correspond to the varying degrees of activation of the central nervous system,
      causing the optimization of behavioral functions, abolition of fatigue and
      drowsiness and enhancing physical and mental working capacity.

PMID- 7627002
TI  - The ancient art of nursing is the story of caring.

PMID- 7627004
TI  - The role of the nurse historian.

PMID- 7627003
TI  - History as shared understanding.

PMID- 7627005
TI  - What it means to be a nurse historian.

PMID- 7627006
TI  - Chapter history as a dynamic legacy.

PMID- 7627007
TI  - Resources offered for chapter heritage.

PMID- 7627008
TI  - Canadian nursing school honors 75 years.

PMID- 7627009
TI  - The history of nursing research in Australia.

PMID- 7627010
TI  - Alpha--the first.

PMID- 7627011
TI  - Educational research exchanged in China.

PMID- 7627012
TI  - Inspired by legacy.

PMID- 7627013
TI  - Electronic library. A collaborative venture for education, Sigma Theta Tau and
      health care agencies.

PMID- 7627014
TI  - Journal indexed in leading science sources.

PMID- 7627015
TI  - Profiles of nursing excellence. Interview by Joellen W. Hawkins.

PMID- 7627016
TI  - Heroes and legacies.

PMID- 7627017
TI  - Instilling courage for change. Sr. Rosemary Donley, SC, RN, PhD, FAAN. Interview
      by Mary Jean Flaherty.

PMID- 7627018
TI  - Reflections on success, challenge.

PMID- 7627019
TI  - Screening for diabetic retinopathy.

PMID- 7627020
TI  - The boundary between health care and social care.

PMID- 7627021
TI  - Performance indicators for general practice.

PMID- 7627022
TI  - Reviewers chosen by authors.

PMID- 7627023
TI  - Nicotine is addictive, rules FDA.

PMID- 7627024
TI  - Britain's breast cancer services need overhaul.

PMID- 7627025
TI  - Woman compensated for removal of ovaries.

PMID- 7627026
TI  - Gynaecologist struck off for catalogue of failures.

PMID- 7627027
TI  - Consultant suspended after hundreds of errors.

PMID- 7627028
TI  - French GPs launch organ donor campaign.

PMID- 7627029
TI  - Israel brings psychiatric care in from cold.

PMID- 7627030
TI  - Pressure group pleads for a healthy planet.

PMID- 7627031
TI  - MPs seek to control medical genetics.

PMID- 7627032
TI  - Senator's bellicosity kindles bigotry.

PMID- 7627033
TI  - Effects of London helicopter emergency medical service on survival after trauma.
AB  - OBJECTIVE: To assess the effect of the London helicopter emergency medical
      service on survival after trauma. DESIGN: Prospective comparison of outcomes in
      cohorts of seriously injured patients attended by the helicopter and attended by
      London ambulance service land ambulances crewed by paramedics. SETTING: Greater
      London. SUBJECTS: 337 patients attended by helicopter and 466 patients attended
      by ambulance who sustained traumatic injuries and died, stayed in hospital three
      or more nights, or had other evidence of severe injury and who were taken to any
      one of 20 primary receiving hospitals. MAIN OUTCOME MEASURE: Survival at six
      months after the incident. RESULTS: After differences in the nature and severity
      of the injuries in the two cohorts were accounted for the estimated survival
      rates were the same (relative risk of death with helicopter = 1.0; 95% confidence
      interval 0.7 to 1.4). An analysis with trauma and injury severity scores (TRISS)
      found 16% more deaths than predicted in the helicopter cohort but only 2% more in
      the ambulance cohort. There was no evidence of a difference in survival for
      patients with head injury but a little evidence that patients with major trauma
      (injury severity score > or = 16) were more likely to survive if attended by the
      helicopter. An estimated 13 (-5 to 39) extra patients with major trauma could
      survive each year if attended by the helicopter. CONCLUSION: Any benefit in
      survival is restricted to patients with very severe injuries and amounts to an
      estimated one additional survivor of major trauma each month. Over all the
      helicopter caseload, however, there is no evidence that it improves the chance of
      survival in trauma.

PMID- 7627034
TI  - Incidence of and mortality from acute upper gastrointestinal haemorrhage in the
      United Kingdom. Steering Committee and members of the National Audit of Acute
      Upper Gastrointestinal Haemorrhage.
AB  - OBJECTIVE: To describe the current epidemiology of acute upper gastrointestinal
      haemorrhage. DESIGN: Population based, unselected, multicentre, prospective
      survey. SETTING: 74 hospitals receiving emergency admissions in four health
      regions in the United Kingdom. SUBJECTS: 4185 cases of acute upper
      gastrointestinal haemorrhage in which patients were aged over 16 years identified
      over four months. OUTCOME MEASURES: Incidence and mortality. RESULTS: The overall
      incidence of acute upper gastrointestinal haemorrhage in the United Kingdom is
      103/100,000 adults per year. The incidence rises from 23 in those aged under 30
      to 485 in those aged over 75. At all ages incidence in men was more than double
      that in women except in elderly patients. 14% of the haemorrhages occurred in
      inpatients already in hospital for some other reason. In 27% of cases (37%
      female, 19% male) patients were aged over 80. Overall mortality was 14% (11% in
      emergency admissions and 33% in haemorrhage in inpatients). In the emergency
      admissions, 65% of deaths in those aged under 80 were associated with malignancy
      or organ failure at presentation. Mortality for patients under 60 in the absence
      of malignancy or organ failure at presentation was 0.8%. CONCLUSIONS: The
      incidence of acute upper gastrointestinal haemorrhage is twice that previously
      reported in England and similar to that reported in Scotland. The incidence
      increases appreciably with age. Although the proportion of elderly patients
      continues to rise and mortality increases steeply with age, age standardised
      mortality is lower than in earlier studies. Deaths occurred almost exclusively in
      very old patients or those with severe comorbidity.

PMID- 7627036
TI  - Changing patterns of iron deficiency anaemia in the second year of life.

PMID- 7627038
TI  - Recurrent spontaneous abortion and polycystic ovarian disease: comparison of two
      regimens to induce ovulation.

PMID- 7627035
TI  - Relation between parasuicide, suicide, psychiatric admissions, and socioeconomic
      deprivation.
AB  - OBJECTIVE: To examine the relations between parasuicide, suicide, psychiatric
      inpatient admissions, and socioeconomic deprivation. DESIGN: Ecological analysis
      with data from routine information systems and the 1991 census. SETTING: 24
      localities in the area covered by the Bristol and District Health Authority
      (population 817,000), consisting of aggregations of neighbouring wards, with an
      average population of 34,000. SUBJECTS: 6089 subjects aged over 10 years admitted
      to hospital after parasuicide between April 1990 and March 1994; 997 suicides
      occurring 1982-91; 4763 subjects aged 10-64 years admitted with acute psychiatric
      illness between April 1990 and March 1994. RESULTS: Localities varied
      significantly in standardised admission ratios for parasuicide and standardised
      mortality ratios for suicide (P < 0.001). Spearman's rank correlation coefficient
      between the standardised mortality ratio for suicide and standardised admission
      ratio for parasuicide was 0.73 (95% confidence interval 0.46 to 0.88).
      Correlation between parasuicide and Townsend score was 0.86 (0.70 to 0.94) and
      between suicide and Townsend score 0.73 (0.46 to 0.88). The partial correlation
      coefficient between suicide and parasuicide after the Townsend score was adjusted
      for was 0.29 (-0.13 to 0.62). The correlation between standardised admission
      ratio for parasuicide and standardised admission ratio for psychiatric illness
      was 0.76 (0.51 to 0.89) and between standardised mortality ratio for suicide and
      standardised admission ratio for psychiatric illness was 0.72 (0.45 to 0.87).
      CONCLUSION: A strong ecological association exists between suicide and
      parasuicide, with socioeconomic deprivation accounting for much of this relation.
      This strong association provides supporting evidence for the importance of social
      policy measures in attaining Health of the Nation targets on mental health.

PMID- 7627037
TI  - Extent of hepatitis B immunisation among medical and dental students.

PMID- 7627039
TI  - Hypersensitivity to retinol palmitate injection.

PMID- 7627040
TI  - Laryngeal oedema after isosorbide dinitrate spray and sublingual nifedipine.

PMID- 7627041
TI  - Tinnitus and ciprofloxacin.

PMID- 7627042
TI  - Predicting acute maxillary sinusitis in a general practice population.
AB  - OBJECTIVE: To evaluate the diagnostic value of symptoms, signs, erythrocyte
      sedimentation rate, and C reactive protein for acute maxillary sinusitis. DESIGN:
      Prospective cohort study. SETTING: Danish general practice in cooperation with
      the otorhinolaryngology and neuroradiology department at Aalborg County Hospital.
      SUBJECTS: 174 patients aged 18-65 years who were suspected by the general
      practitioner of having acute maxillary sinusitis. MAIN OUTCOME MEASURE: The
      independent association of symptoms, signs, erythrocyte sedimentation rate, and
      concentration of C reactive protein in patients with acute maxillary sinusitis
      defined as purulent or mucopurulent antral aspirate. RESULTS: Only raised
      erythrocyte sedimentation rate (P = 0.01) and raised C reactive protein (P =
      0.007) were found to be independently associated with a diagnosis of acute
      maxillary sinusitis. The combination of the two variables had a sensitivity of
      0.82 and a specificity of 0.57. CONCLUSION: Erythrocyte sedimentation rate and C
      reactive protein are useful diagnostic criteria for acute maxillary sinusitis.

PMID- 7627043
TI  - Videotaping of general practice consultations: effect on patient satisfaction.

PMID- 7627044
TI  - How to ensure that guidelines are effective.

PMID- 7627046
TI  - ABC of medical computing. Getting your thoughts on paper.

PMID- 7627045
TI  - Make an application for flexible (part time) training.
AB  - Part time training posts are advertised in the BMJ each year in August or
      September in an advertisement placed by the Department of Health. Although the
      advertisement is placed by the department and manpower approvals are allocated
      centrally, each region runs its own scheme, and the first person to approach is
      the regional postgraduate dean (most regions have an assistant dean responsible
      for flexible training). If an application is successful then part time trainees
      are interviewed by the same appointments committee as full time applicants and
      they are judged by the same criteria. Manpower approval is granted to applicants
      who reach the same standard as full time applicants, but there may be a waiting
      list if there are more suitable applicants than training places available. The
      next stage is to gain educational approval from the relevant higher training
      committee for the proposed training programme, followed by funding from the
      region.

PMID- 7627047
TI  - Cocaine and adrenaline paste: a fatal combination?

PMID- 7627048
TI  - Qualitative interviews in medical research.
AB  - Much qualitative research is interview based, and this paper provides an outline
      of qualitative interview techniques and their application in medical settings. It
      explains the rationale for these techniques and shows how they can be used to
      research kinds of questions that are different from those dealt with by
      quantitative methods. Different types of qualitative interviews are described,
      and the way in which they differ from clinical consultations is emphasised.
      Practical guidance for conducting such interviews is given.

PMID- 7627049
TI  - Folic acid and the prevention of neural tube defects. Chapati flour should be
      fortified as well.

PMID- 7627050
TI  - Folic acid and the prevention of neural tube defects. Most pregnant women do not
      take folic acid.

PMID- 7627051
TI  - Folic acid and the prevention of neural tube defects. Power of the state in
      attitudes to health has already expanded too much.

PMID- 7627052
TI  - Folic acid and the prevention of neural tube defects. Preconceptional
      supplementation is impractical.

PMID- 7627053
TI  - Evidence based medicine. Example was flawed.

PMID- 7627054
TI  - Evidence based medicine. Megatrials are subordinate to medical science.

PMID- 7627055
TI  - Evidence based medicine. Must be applied critically.

PMID- 7627056
TI  - Evidence based medicine. Quality cannot always be quantified.

PMID- 7627057
TI  - Evidence based medicine. No guidance is provided for situations for which
      evidence is lacking.

PMID- 7627058
TI  - Evidence based medicine. Journal of Evaluation in Clinical Practice will start
      publication in September.

PMID- 7627059
TI  - Compliance with medication among elderly people. Study of self medication on
      elderly people was flawed.

PMID- 7627060
TI  - Evidence based medicine. Accurate references are important.

PMID- 7627061
TI  - Prophylactic aspirin and peptic ulcer bleeding. Patients warned of a bleed may be
      more vigilant.

PMID- 7627062
TI  - Interventions in OXCHECK study waste resources.

PMID- 7627063
TI  - Mineralocorticoid effects of high dose hydrocortisone.

PMID- 7627064
TI  - Treatment of childhood asthma.

PMID- 7627065
TI  - Assessing coronary risk.

PMID- 7627066
TI  - Hospital security.

PMID- 7627067
TI  - Handling scientific fraud. Pearce's editors were not to blame.

PMID- 7627068
TI  - Handling scientific fraud. BMJ nurtures spoof publication.

PMID- 7627069
TI  - Handling scientific fraud. Clinical fraud is common.

PMID- 7627070
TI  - Handling scientific fraud. Prospective registration of health care research would
      help.

PMID- 7627071
TI  - Osteoporosis.

PMID- 7627072
TI  - Smuggling of tobacco in Europe.

PMID- 7627073
TI  - Strategies for reducing coronary risk factors in primary care.

PMID- 7627074
TI  - Measurement of bone density in osteoporosis.

PMID- 7627075
TI  - Rationing. Medical profession should develop consensus on health priorities via
      debates.

PMID- 7627076
TI  - The future of fundholding.

PMID- 7627077
TI  - Treatment of lupus syndromes.

PMID- 7627078
TI  - Smoking among secondary schoolchildren.

PMID- 7627079
TI  - Vaccinations for travellers.

PMID- 7627080
TI  - What happened to care?

PMID- 7627081
TI  - Chemoprevention and oral cancer--(more) trials and (more) tribulations.

PMID- 7627082
TI  - Oral precancer: preventive and medical approaches to management.
AB  - Leukoplakias are among the most common potentially malignant oral lesions. Some
      are idiopathic, others are related to habits such as tobacco and/or alcohol use.
      Medical management includes reducing or abandoning these habits, increasing the
      intake of fruit and vegetables in the diet, and possibly the use of active
      agents. Retinoids, carotenoids and topical cytotoxic agents show promise, and
      newer therapies are on the horizon.

PMID- 7627083
TI  - Effect of local administration of epidermal growth factor on 9,10-dimethyl-1,2
      benzanthracene-induced tumour formation in hamster cheek pouch.
AB  - The effect of local administration of epidermal growth factor (EGF) on 9,10
      dimethyl-1,2-benzanthracene (DMBA)-induced tumour formation was investigated in a
      hamster cheek pouch carcinogenesis model. DMBA-treated hamsters underwent either
      sialoadenectomy (groups 1 and 2) or a sham operation (groups 3 and 4).
      Thereafter, EGF (groups 1 and 3) or vehicle (groups 2 and 4) was applied to the
      cheek pouches for 6 weeks. Fourteen weeks after the beginning of the experiment,
      the number of cheek pouch tumours was significantly greater in EGF-treated
      hamsters than in vehicle-treated hamsters, irrespective of whether the
      submandibular glands had been removed. The number of forestomach tumours, induced
      by DMBA application to the cheek pouches, was also increased by EGF. These
      results suggest that EGF applied from the luminal side of the mucosa stimulates
      tumour formation in the hamster cheek pouch and forestomach.

PMID- 7627084
TI  - Chemoprevention of oral carcinogenesis.

PMID- 7627085
TI  - Cytokinetic studies of oral cancer cells using bromodeoxyuridine labelling in
      relation to factors influencing prognosis.
AB  - Cytokinetics of 27 untreated oral squamous cell carcinomas were evaluated by in
      vitro bromodeoxyuridine (BrdU) labelling. A mononuclear cell suspension was
      prepared for the labelling using collagenase and DNase treatment. The labelled
      cells were visualised by immunofluorescence staining with an anti-BrdU monoclonal
      antibody. The labelling index (LI%) was calculated by determining the percentage
      of BrdU labelled cells. The LIs of the carcinomas ranged from 3.8 to 19.2%. The
      LIs of poorly-differentiated (HG3) tumours were 2-3-fold higher compared with
      those of well-differentiated (HG1) and moderately-differentiated (HG2)
      carcinomas. Results also showed statistically significant (P < 0.0005) increases
      in LIs from nuclear grade 1 (NG1) to nuclear grade 3 (NG3) carcinomas. Higher LIs
      were observed in stage III/IV (10.82 +/- 4.62; 10.36 +/- 4.90) than those in
      stage I (6.87 +/- 2.09) and II (7.14 +/- 1.87) carcinomas. A significant (P <
      0.0005) difference in LI values was found between the patients with positive and
      negative lymph nodes. Good correlation (r = 0.77) was exhibited between the LI
      values and mitotic counts (MC) of the specimens. These results on oral cancer
      cell proliferation seem to have prognostic implications.

PMID- 7627086
TI  - Cancer of the mobile tongue in Mexico. A retrospective study of 170 patients.
AB  - Histological reports of 170 patients with cancer of the mobile tongue between
      1977 and 1989 were identified at the Instituto Nacional de Cancerologia (INCan),
      in Mexico City. Demographic, clinical and histological information was
      retrospectively reviewed. Chi-square, Student's t-test and Wilcoxon rank-sum test
      were applied for comparisons, and Kaplan-Meier curves, log-rank test and Cox
      proportional hazards for survival analysis. Of the 161 patients with mobile
      tongue squamous cell carcinoma (MTSCC), 104 (65%) were males and 57 (35%) were
      females. The mean age was 60 years old (range 19-91). T1 and T2 lesions comprised
      35%, T3 and T4 lesions 65%. There was a statistically significant association
      between size of the tumour and lymph node involvement (P < 0.0001). The
      proportion of cases with advanced disease was 80% for males and 57% for females
      (P = 0.008). The 5-year survival rate was 16% (CI 10.2-22.8%). Cancer of the
      mobile tongue in Mexico still has a poor prognosis. Efforts should be made to
      reduce the delay in diagnosis of MTSCC, in order to increase the cure rates and
      improve the quality of life of the patients.

PMID- 7627087
TI  - A case study of nutrient intervention of oral precancerous lesions in India.
AB  - Tobacco chewing and/or smoking are strongly related to several cancers, mainly of
      the upper aerodigestive tract. Several studies on diet and cancer links suggest
      that micronutrients, particularly antioxidant vitamins and minerals, are risk
      modifiers of cancers of epithelial origin. This study looks at the impact of
      micronutrients such as vitamin A, riboflavin, zinc and selenium as intervention
      agents in subjects with and without precancerous lesions in a high risk group
      (reverse smokers of chutta-rolled tobacco leaf). Reverse smokers from four
      villages were enrolled in the study. 150 subjects were supplemented with four
      nutrients, namely vitamin A, riboflavin, zinc and selenium in the form of a
      capsule twice a week for 1 year. 148 controls received a placebo capsule
      containing lactose for the same period. Clinical history and anthropometric data
      were collected from all the subjects and a clinical photograph of the palate was
      taken. Micronutrients were estimated in random blood collected from a sub-sample
      before and after the study. Micronutrients improved the vitamin A, riboflavin and
      selenium nutriture in the supplemented group with a concomittant regression of
      precancerous lesions present on the palate. Clinically complete remission of
      white, red and combination lesions was seen in 57% of subjects on supplements
      whereas 8% on placebo showed a positive response. Further progression of these
      lesions was seen in 10% of the supplemented group compared with 47% in the
      placebo group (P < 0.001). In the non-lesion group, new lesions appeared in 12%
      on supplements while more than 38% on the placebo developed new lesions (P <
      0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7627088
TI  - Cervical lymph node metastasis: model for study of head/neck melanoma.
AB  - Tumour cells spread from primary tumours to form distant metastatic deposits by
      both lymphatic and blood routes. Melanomas occurring in the head and neck have an
      extremely poor prognosis largely in part due to late detection resulting in
      extensive dissemination by lymphatic metastasis. The purpose of this study was to
      develop an animal model for the study of head and neck melanoma metastasis. B16
      F1 parental cells were injected into the subcutis of the ear mid-lobule of
      C57BL/6 mice. At selected time periods after inoculation, animals were killed by
      cervical dislocation and autopsied. In some animals tumours had spread to the
      cervical lymph nodes. Examination of organ systems revealed no evidence of
      distant metastases. Histological examination of the cervical lymph nodes revealed
      tumour invasion, beginning at a subcapsular sinus and progressing into the
      paracortical sinuses. Cells from these nodes were adapted to cell culture,
      expanded by passage and reinjected into new mice. Subsequent generations of lymph
      node-selected B16 cell lines were more metastatic than their parental cell line,
      as evidenced by a more rapid appearance of cervical lymph node and extensive node
      invasion. Morphologically, the lymph node-selected B16 cell lines were more
      dendritic than the original B16-F1 parent line and had a larger number of
      pseudopodial projections. Perhaps increased expression of pseudopods by the
      metastatic variants may allow for greater migratory potential and hence increased
      metastatic ability. These results indicate that highly mobile variant B16
      sublines can be selected with an increased capacity for cervical lymphatic
      metastasis.

PMID- 7627090
TI  - Surveillance of oral cultures for Enterobacteriaceae during bone marrow
      transplantation.
AB  - Bone marrow-transplanted patients can suffer from severe life-threatening
      infections. Oral bacterial cultures were collected from a group of 40 patients
      prior to and following bone marrow transplantation every 3 days, following
      initial preparation and eradication of oral infections. The samples were grown on
      the Titertek-Enterobac kit specific for Enterobacteriaceae. In 426 oral cultures
      30.5% grew gram-negative bacteria, 76.6% of them were Enterobacteriaceae. young
      male patients had 8.3% positive cultures at the study start, a percentage which
      constantly increased during later periods. Older patients did not follow the same
      pattern. Also, the allogeneic transplantation group had a higher percentage of
      Enterobacteriaceae than the autologous group (49.0 versus 19.5%). In blood
      cultures 18 out of the 94 positive ones showed the presence of
      Enterobacteriaceae. The most commonly found microorganisms in oral cultures were
      Klebsiella oxytoca (23%), Enterobacter cloacae (18%) and Klebsiella pneumoniae
      (15%). The decrease in the positive oral cultures from 35.0% during the
      pretransplantation period to 5.4% close to the transplantation, demonstrates that
      the preparatory protocol used for the prevention of oral infections was highly
      effective.

PMID- 7627089
TI  - p53 expression: a potential biomarker for risk of multiple primary malignancies
      in the upper aerodigestive tract.
AB  - The concept of field cancerisation assumes that in head and neck cancer patients
      (HNCP) with multiple malignancies the second primary cancers may arise
      independently from the entire upper aerodigestive tract as a consequence of
      massive exposure to common carcinogens. Since mutations and/or overexpression of
      the p53 tumour suppressor gene represent a genetic alteration frequently
      occurring in HNCP, we analysed immunocytochemically p53 oncoprotein expression in
      first primary, second primary cancers and in macroscopically uninvolved normal
      epithelium from different sites of the upper aerodigestive tract from 12 HNCP
      with multiple malignancies, in comparison with p53 expression in biopsy specimens
      of the upper aerodigestive tract from 5 non-neoplastic heavy smokers, as
      controls. In patients with multiple malignancies 6 cases (50%) showed positive
      staining of both first and second primaries, whereas 3 (25%) had positive
      labelling of first primary cancer but not of the subsequent second primary, 2
      (17%) patients showed p53 expression only in the second primary cancer, and
      finally only 1 patient (8%) showed no p53 immunoreactivity in both first and
      second primary tumours. Moreover, 10 out of 12 (83%) HNCP with multiple cancers
      showed p53-positive staining in the normal epithelium from different sites of the
      upper aerodigestive tract, also at a significant distance from the site of first
      and second primary malignancies. contrast, sporadic p53 immunostaining was
      observed only in three out of 35 (8.5%) specimens from non-neoplastic controls.
      In addition, in 4 HNCP with multiple tumours the histological examination of
      apparently normal epithelium from the upper aerodigestive tract revealed signs of
      moderate or severe dysplasia, and in 1 case an in situ carcinoma.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7627091
TI  - Heat shock protein expression in oral epithelial dysplasia and squamous cell
      carcinoma.
AB  - Heat shock protein (HSP) expression is upregulated in tumour cells and,
      therefore, HSP expression is a likely marker of the malignant potential of oral
      epithelial lesions. Furthermore, the 70-kDa HSP (HSP 70) is implicated in the
      degree of tumour differentiation, the rate of tumour proliferation and the
      magnitude of the anti-tumour immune response. Accordingly, the distribution and
      intensity of HSP 70 expression was assessed in the epithelial compartment of oral
      squamous cell carcinoma (SCC, n = 29), dysplastic oral epithelium (n = 18) and
      benign oral mucosal lesions (n = 22) using avidin-biotin complex
      immunohistochemistry and microdensitometry under standardised conditions.
      Staining intensity was recorded in kilo-ohms (k omega). Normal oral mucosa (n =
      15) was used for comparison, and results were analysed using Kruskall-Wallis and
      Fisher's exact tests. The distribution of HSP 70 expression in well
      differentiated SCC was significantly different from that in poorly differentiated
      SCC (P < 0.05), the latter demonstrating a more focal staining pattern. Median
      staining intensity in SCC (6.22 k omega), epithelial dysplasia (9.61 k omega) and
      the benign oral mucosal lesions (8.28 k omega) was significantly greater than
      that in normal oral mucosa (5.64 k omega; P < 0.05). Staining intensity in poorly
      differentiated SCC (7.66 k omega) was greater than that in moderately
      differentiated SCC (4.77 k omega), although this result just failed to reach
      statistical significance (P = 0.06). These results suggest that, as employed
      currently, HSP 70 expression is not a definitive marker of oral malignancy or
      malignant potential.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7627092
TI  - Head and neck carcinoma in Fanconi's anaemia--report of a case and review of the
      literature.
AB  - Fanconi's anaemia (FA) is a rare autosomal recessive syndrome characterised by
      progressive lethal pancytopenia, skeletal abnormalities, hyperpigmentation and
      increased chromosomal aberrations. A high incidence of leukaemia and
      hepatocellular and squamous cell carcinomas (SCC) have been reported in FA
      patients. A rare case of SCC of the dorsum of the tongue in a FA patient is
      presented. A review of the reported cases of head and neck carcinoma in FA
      patients shows a different male:female ratio than previously reported, and a high
      incidence of carcinoma of the tongue.

PMID- 7627093
TI  - A novel line of transgenic mice (RSV/LTR-bGH) expressing growth hormone in
      cardiac and striated muscle.
AB  - In order to further investigate the deleterious effects of GH overexpression, we
      generated a novel line of transgenic mice featuring stable and specific
      expression of bovine GH in the heart and striated muscle. A DNA construct,
      containing a region with promoter activity from the Long Terminal Repeat of Rous
      Sarcoma Virus (RSV-LTR) and the entire structural gene of bovine GH (bGH), was
      microinjected by standard techniques in male pronuclei of fertilized mice eggs.
      Transgenic mice expressed bGH mRNA in the heart and striated muscle starting at 5
      6 weeks of age. They featured circulating levels of a 22 kDa form of bGH up to
      700 ng/ml and enhanced growth starting at 6 weeks of age. No pathologic changes
      of the myocardium and striated muscle fibers, other than hypertrophy, were
      noticed, although severe glomerulosclerosis and liver alteration occurred in
      older mice. Future studies on this new line of transgenic GH mice and integration
      with the existing data might improve our understanding of the molecular mechanism
      underlying the detrimental effects of elevated GH levels on various organs and
      functions.

PMID- 7627094
TI  - A critical assessment of the use of microculture tetrazolium assays to measure
      cell growth and function.
AB  - Microculture tetrazolium assays (MTAs) are being widely applied to probe the
      relationships between cell survival, growth, and differentiation and also to
      investigate associations between compromised cell metabolism, oxidative stress,
      and programmed cell death as occurs in apoptosis. MTAs rely upon the cellular
      reduction of tetrazolium salts to their intensely coloured formazans. The
      resulting colorimetric assays form the basis of exceptionally precise systems
      which are technically amenable and capable of a high throughput of samples. As a
      consequence, MTAs are being used to monitor responses to both extracellular
      activators and toxic agents in disciplines as diverse as radiobiology and
      endocrinology. We review the chemistry and histochemical applications of
      tetrazolium salts and subsequently discuss the criteria for their use in MTAs.
      These assays are one of the latest examples of the application of the
      tetrazolium/formazan system to cell biology. We outline current views on the
      mechanisms of the bioreduction of tetrazolium salts. These probably combine to
      reflect the integrated pyridine nucleotide dependent redox state of the cell. We
      try to illustrate how an understanding of these mechanisms helps to avoid some of
      the pitfalls of the MTA systems. There is now for example, extensive evidence
      that changes in cell culture environments, such as glucose supply or pH of the
      medium, influence the reduction of tetrazolium salts and thereby introduce
      artefacts into MTAs. Finally, we provide examples of situations in which MTAs can
      be used to complement other more established experimental systems. They then act
      as unique probes with which to investigate changes in the redox state of the
      cell. These changes are associated with regulation of cell growth, proliferation
      and differentiation and conversely, the different pathways leading to cell death.

PMID- 7627095
TI  - Activation of MAP kinase in Swiss 3T3 fibroblasts by insulin-like growth factor
      I.
AB  - A peak of cytosolic myelin basic protein kinase activity was observed at 2-5 min
      after addition of 10 nM insulin-like growth factor-I (IGF-I) to Swiss 3T3
      fibroblasts. Analysis of the induced kinase activity by chromatography,
      immunodetection and in situ kinase assay suggests that this represents a 1.8- to
      3.5-fold increase in the activity of p42 mitogen-activated protein kinase.
      Addition of insulin at 10 nM also resulted in an increased kinase activity in
      these respects, however, only to approximately 60% of that induced by IGF-I. A
      similar quantitative relation between the effects of insulin and IGF-I was found
      for induction of lipid and glycogen synthesis from [14C- (U)]-D-glucose. However,
      incorporation of 3H-L-leucine into protein was stimulated to the same extent by
      the two agents. The effect of 10 nM insulin on proliferation, measured as
      tetrazolium dye reduction, was only 18% of that induced by 10 nM IGF-I. The
      obtained data suggest that cytosolic mitogen-activated protein kinase activation
      may constitute a signalling pathway for glucose metabolism, and especially
      glycogen synthesis, induced by peptides of the insulin superfamily.

PMID- 7627096
TI  - Cultural diversity and case management.

PMID- 7627097
TI  - Case management in long-term care: exploring its status, trends, and issues.
AB  - After briefly reviewing the goals of long-term care, the goals of case
      management, and the models in which they currently function, this article focuses
      on the importance of recognizing the differences in culture, values, ideology,
      and policies in which case management takes place and the main issues confronting
      case managers. These issues can be divided into two broad categories: (a)
      policies that have serious implications for case management but over which case
      managers have little or no individual control; and (b) those in which case
      managers are directly involved, partly because of the context in which they work
      and partly because of the case management function itself. The issues must be
      addressed so that case managers individually and collectively can do the best
      possible job in serving vulnerable subpopulations in need of long-term care.

PMID- 7627098
TI  - Linking frontline work and state-of-the-art knowledge: a community exchange
      system.
AB  - When challenged by complex medical and social conditions, local providers must
      participate in information exchanges, resource sharing, continuing education, and
      service coordination. A community exchange system, flexible enough to share and
      adapt new knowledge, and able to provide continuing multidisciplinary training
      and education across different practice settings, was established for the
      prevention and treatment of HIV/AIDS in East Harlem, New York City. The HIV/AIDS
      community exchange system supports linkages among disciplines within a medical
      center, communication among the local community-based organizations, and networks
      between the two settings. The system, as a model, is applicable to complex socio
      medical problems such as diabetes, substance abuse, violence, tuberculosis, or
      geriatrics.

PMID- 7627099
TI  - Restraining impaired elders in the home environment: legal, practical, and policy
      implications.
AB  - Since the late 1980s, a combination of regulation and education has brought about
      tremendous changes in practices in nursing homes, and to a lesser extent
      hospitals, concerning the use of physical and chemical restraints on patients.
      However, case managers often seek to negotiate home living arrangements for
      impaired older persons as a less restrictive or intrusive alternative than
      institutional placement. This article moves the discussion about the legal and
      ethical propriety of restraints to this home setting. Questions are raised about
      theoretical legal implications, practical enforcement issues, and public policy
      dilemmas when restraints are applied to older, impaired individuals in the home
      environment either by professional agency personnel or by the individual's
      family. Specific questions for case managers are highlighted.

PMID- 7627100
TI  - Educating case managers for culturally competent practice.
AB  - This article provides a rationale for incorporating cultural competence into case
      management practice and examines the content required in educational programs for
      preparing case managers with appropriate and relevant knowledge, values, and
      skills. Cultural competence and related concepts are defined and applied in the
      context of case management. A number of required skills for educating case
      managers for culturally competent practice are presented. Becoming culturally
      competent is a developmental process involving self-awareness, understanding
      others from a cultural frame of reference, and acquiring the skills to provide
      culturally relevant and culturally sensitive practice.

PMID- 7627101
TI  - A team approach to geriatric case management.
AB  - Providing high-quality, comprehensive care for elderly Americans is becoming
      increasingly challenging because of the aging of society, the shortage of primary
      care physicians, and rising health care costs. These trends are encouraging
      health care delivery systems to adopt alternative models of patient care. This
      article reports on one such model, the complementary practice model, which
      incorporates a team approach to geriatric case management. The complementary
      practice model targets the frail elderly who are near the end of life, or are at
      highest risk for either hospitalization or cognitive decline. It includes a
      diverse, multidisciplinary team to provide patient care by involving the patient,
      family, physician, nurse practitioner, social worker, and registered nurse as
      core team members. This team approach assesses and identifies patients' problems,
      utilizes the expertise of multiple health care disciplines, and encourages
      patients and families to be active participants in developing and implementing
      the case management plan.

PMID- 7627102
TI  - Words of wisdom for staff development educators.

PMID- 7627103
TI  - Keeping adult learning principles alive.

PMID- 7627104
TI  - Education under the JCAHO agenda for change.

PMID- 7627105
TI  - Self-directed learning. Info-letters: the cure for the "out of touch" syndrome.

PMID- 7627106
TI  - Administrative issues. Promoting political involvement.

PMID- 7627107
TI  - Marketing your education department.

PMID- 7627109
TI  - The show must go on: the drama of posttraumatic restructuring syndrome.

PMID- 7627108
TI  - What to do when the process to efficiency becomes inefficient: streamlining CQI.

PMID- 7627110
TI  - Tips for ethical audiovisual taping.

PMID- 7627111
TI  - Regulatory requirements: from woe to dough.

PMID- 7627112
TI  - Preparing staff nurses for specialty certification.

PMID- 7627113
TI  - Even if you're right--if you're rude, then you're wrong.

PMID- 7627114
TI  - The role of volunteers: what educators need to know.

PMID- 7627115
TI  - Long-term care. Balancing act: the one person staff development show.

PMID- 7627116
TI  - Age-specific competencies: strategies for implementation.

PMID- 7627117
TI  - Designing an integrated education calendar.

PMID- 7627118
TI  - Production of reactive oxygen-derived species by redox reactions between
      Fe(II)cytochrome c and oxygen. A kinetic study.
AB  - In aerated water solutions Fe(II)Cytochrome c is slowly oxidized to
      Fe(III)Cytochrome c by molecular oxygen, from which superoxide anion radicals are
      produced (kobs = 2.7 x 10(-4) min-1 at 37 degrees C and pH = 7.3). The biological
      importance of this reaction has been evidenced by kinetic investigations in the
      presence of scavengers. In the presence of Superoxide dismutase the oxidation
      rate is strongly enhanced (kobs = 3 x 10(-3) min-1 at 37 degrees C). Catalase and
      mannitol reduce the rate constant values by 50% and 25% respectively either in
      the presence or in the absence of Superoxide dismutase: differences between rate
      constants correspond to the differences in stoichiometric redox ratios indicating
      that hydrogen peroxide and hydroxyl radicals are formed subsequently to the
      production of superoxide anion radicals.

PMID- 7627119
TI  - Activity of the antioxidant enzyme, glutathione peroxidase, on autosomal dominant
      polycystic kidney disease patients.
AB  - Reactive oxygen species are generated physiologically in cells with a significant
      increase in certain pathological conditions, such as inflammation, cancer, aging,
      degenerative disease. If endogenous antioxidant systems, in our study represented
      by glutathione peroxidase, are exceeded by this oxidant flux, tissue injury may
      occur. Activity of glutathione peroxidase (GPx) was determined using Beutler's
      modified spectrophotometric assay in erythrocytes from autosomal dominant
      polycystic kidney disease patients. Activity of glutathione peroxidase was
      significantly (at p < 0.0001) lower there (17.75 +/- 3.69 U/g haemoglobin)
      compared to the control group (23.26 +/- .61 U/g Hb). Lower antioxidant enzyme
      defence system of ADPKD patients, here represented by GPx, can potentiate injury
      caused by free radicals and possibly play a role in the progression of autosomal
      dominant polycystic kidney disease.

PMID- 7627120
TI  - Lipid peroxidation and superoxide dismutase activity in umbilical and maternal
      blood.
AB  - Oxygenation of both mother and child tissues oscillate frequently during labour.
      We tested the lipid peroxidation caused by reactive oxygen species which are
      produced in consequence of tissue reoxygenation and the inactivation of these
      species by the maternal and newborn superoxide dismutase. Total malondialdehyde
      in concentrations (mean +/- SE) of 1.04 +/- 0.17, 1.57 +/- 0.22, 1.33 +/- 0.14
      and 1.36 +/- 0.21 mumol/L was found in maternal plasma and red blood cells and
      newborn plasma and red blood cells, respectively, after uncomplicated deliveries
      and 4.93 +/- 1.34, 7.12 +/- 1.37, 4.77 +/- 1.29 and 7.37 +/- 1.51 mumol/L,
      respectively, after deliveries with clinical signs of foetal hypoxia. In
      newborns, erythrocyte superoxide dismutase activity reached only 82% of the
      maternal level (p < 0.05). The results indicate that the maternal and foetal
      antioxidant defence systems can be overloaded during deliveries with abnormal
      oxygenation, where increased lipid peroxidation occurred.

PMID- 7627121
TI  - Mitochondrial calcium uptake in bovine frozen sperm.
AB  - Mitochondria from bovine frozen semen are capable of preserving oxidative energy.
      The purpose of this work was to study calcium uptake by the inner mitochondrial
      membrane which, together with the plasmatic membrane, is involved in spermatic
      motility and viability regulation. Mitochondrial coupling was confirmed. In the
      active state, there was a drop in oxygen uptake rate using calcium concentrations
      ranging from 20 to 100 microM. In the resting state, 75 microM calcium
      concentration mimicked the active respiration state. In both states,
      concentrations greater than 100 microM induced mitochondrial uncoupling. Maximal
      mitochondrial uptake was recorded in the active state with 10 microM lactate. At
      calcium concentrations greater than 100 microM, there was a drop in mitochondrial
      calcium uptake for both respiration states. The ability to preserve oxidative
      energy allows the spermatozoon to take up mitochondrial calcium, thus regulating
      its functional activity.

PMID- 7627122
TI  - Effects of acetaminophen on methemoglobin, superoxide dismutase and Na(+)-K+
      ATPase activities of human erythrocytes.
AB  - It is established that acetaminophen exhibits oxidative behaviour. The effects of
      acetaminophen (0.3-14.5 microM) on methemoglobin levels, superoxide dismutase and
      Na(+)-K+ ATPase activities of normal and vitamin E or vitamin C pretreated
      erythrocytes were investigated. In acetaminophen incubated erythrocytes,
      methemoglobin concentration and superoxide dismutase activity were increased in a
      dose and incubation-time dependent manner, the activity of Na(+)-K+ ATPase was
      decreased by acetaminophen treatment. Vitamin E (1mg/dl of erythrocyte
      suspension) or vitamin C (1mg/dl of erythrocyte suspension) provided partial
      protection of hemoglobin, superoxide dismutase and Na(+)-K+ ATPase against
      acetaminophen action. Vitamin E was more effective than vitamin C.

PMID- 7627123
TI  - Characterization of gamma-crystallin from a catfish: structural characterization
      of one major isoform with high methionine by cDNA sequencing.
AB  - gamma-Crystallin is the major and most abundant lens protein present in the eye
      lens of most teleostean fishes. To facilitate structural characterization of
      gamma-crystallins isolated from the lens of the catfishes (Clarias fuscus), a
      cDNA mixture was synthesized from the poly(A)+mRNA isolated from fresh eye
      lenses, and amplification by polymerase chain reaction (PCR) was adopted to
      obtain cDNAs encoding various gamma-crystallins. Plasmids of transformed E. coli
      strain JM109 containing amplified gamma-crystallin cDNAs were purified and
      prepared for nucleotide sequencing by the dideoxynucleotide chain-termination
      method. Sequencing more than five clones containing DNA inserts of 0.52 kb
      revealed the presence of one major isoform with a complete reading frame of 534
      base pairs, covering a gamma-crystallin (gamma M1) with a deduced protein
      sequence of 177 amino acids excluding the initiating methionine. It was of
      interest to find that this crystallin of pI 9.1 contains a high-methionine
      content of 15.3% in contrast to those gamma-crystallins of low-methionine content
      from most mammalian lenses. Sequence comparisons of catfish gamma M1-crystallin
      with those published sequences of gamma-crystallins from carp, bovine and mouse
      lenses indicate that there is approx. an 82% sequence homology between the
      catfish and the carp species of piscine class whereas only 51-58% homology is
      found between mammals and the catfish. Moreover the differences in the hydropathy
      profiles for these two groups of gamma-crystallins, i.e. one with a high
      methionine content from teleostean fishes and the other with a low-methionine
      content from mammalian species, reflect a distinct variance in the polarity
      distributions of surface amino acids in these crystallins.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7627124
TI  - Dimethyl sulphoxide alters mitogen induced production of diacylglycerol and GTP
      binding to plasma membranes in mouse embryo fibroblasts.
AB  - Dimethyl sulphoxide (DMSO) is a polar solvent often used as an inducer of
      erythroid differentiation. In order to elucidate the mode of action of DMSO, we
      studied its effects on two early events in signal transduction, namely
      diacylglycerol (DAG) production and guanosine triphosphate (GTP) binding. Mouse
      embryo fibroblasts showed a bimodal profile of diacylglycerol synthesis in the
      presence of DMSO. Platelet derived growth factor (PDGF) mediated synthesis of
      diacylglycerol synthesis was inhibited by DMSO. Also DMSO down regulated serum
      induced GTP-binding to isolated plasma membranes of mouse embryo fibroblasts.
      However, the control and the ras (T24) oncogene transformed Rat-2 cells did not
      show any increase in GTP-binding on serum stimulation while showing a marginal
      decrease in GTP-binding in the presence of DMSO. DMSO may hence act by inhibiting
      the perpetuation of mitogenic signal transduction at an early stage.

PMID- 7627126
TI  - Determination of magnesium ion by use of the coupled-enzyme method with pyruvate
      kinase and lactate dehydrogenase.
AB  - We developed a new convenient method for determination of magnesium ion
      concentrations by use of magnesium ion-dependent enzymes; pyruvate kinase and
      lactate dehydrogenase. This method is based on the determination of the reaction
      rate of pyruvate kinase which uses MgADP- as substrate. The reaction rate of
      pyruvate kinase is dependent upon the formation of the complex with ADP and
      magnesium ion and the amount of the complex is dependent upon that of magnesium
      ion. The reaction rate of pyruvate kinase can be easily and
      spectrophotometrically determined by using lactate dehydrogenase and NADH as the
      decreased amount of absorbance at 340 nm.

PMID- 7627125
TI  - Plant annexin form homodimer during Ca(2+)-dependent liposome aggregation.
AB  - The annexin (p35) was isolated from the fruits of green pepper (Capsicum annum).
      The partial amino acid sequence of p35 was analyzed. p35 had an endonexin fold as
      annexin consensus sequences. Purified p35 had other annexin like characters such
      as strongly bind to phosphatidylserine and phosphatidylinositol, phospholipase A2
      inhibition and liposome aggregation. The zero-length crosslinking assay revealed
      that p35 formed a homodimer during Ca(2+)-dependent liposome aggregation.

PMID- 7627127
TI  - N,S-bis-fluorenylmethoxycarbonylglutathione: a new, very potent inhibitor of
      mammalian glyoxalase II.
AB  - A very potent competitive inhibitor of mammalian glyoxalase II activity, N,S-bis
      fluorenylmethoxycarbonylglutathione (DiFMOC-G) has been synthesized and
      characterized. The Ki value for inhibition of glyoxalase II purified from calf
      liver is 0.08 microM. The Ki values for glyoxalase I inhibitions range from 285
      to 500 fold higher than the values obtained for glyoxalase II inhibitions,
      depending on the source of the enzyme. Among other enzymes involved in
      glutathione metabolism, such as glutathione S-transferase, glutathione reductase,
      and glutathione peroxidase, only glutathione S-transferase is inhibited to a
      small extent by DiFMOC-G. Diesters of DiFMOC-G were prepared in order to improve
      transport of DiFMOC-G into mammalian tumor cells (rat adrenal pheochromocytoma,
      PC-12) in culture. Among the diesters synthesized, diisopropyl DiFMOC-G was found
      to be the most inhibitory to cell viability, with a [I]0.5 value of 3 microM.

PMID- 7627128
TI  - Human macrophage colony stimulating factor (HM-CSF) expressed in baculovirus
      infected insect cells is biologically active in its monomeric form.
AB  - hM-CSF was reported to have biological activity only in a dimeric form. Using
      oligonucleotide-directed mutagenesis of hM-CSF (1-149aa) cDNA, we have
      substituted Ser31 for Cys31 which forms intermolecular disulfide bond in native
      hM-CSF. The mutant hM-CSF cDNA was expressed in insect BmN cells using
      baculovirus as a vector under the control of polyhedrin promoter. Biological
      activity analysis and radioligand receptor assay both showed that there was
      little difference between the mutant hM-CSF and the native dimeric hM-CSF. These
      results strongly support that the biologically active human M-CSF in its
      monomeric form can be expressed in recombinant baculovirus infected insect cells.

PMID- 7627129
TI  - Phosphofructokinase binding to myofibrils in fish muscle: influences of ionic
      strength and metabolite levels on enzyme complex formation.
AB  - The interaction of 6-phosphofructo-1-kinase (PFK) with myofibrils was assessed
      using the purified proteins from rainbow trout white skeletal muscle. More than
      70% of PFK activity was bound at pH values between 6 and 7 but higher pHs
      dissociated the complex. Increasing salt concentrations also reduced PFK binding,
      with greater sensitivity to salt at pH 7.0 vs pH 6.6. Substrates and allosteric
      effectors also reduced enzyme binding to myofibrils; 50% of enzyme was released
      at 0.23, 0.24, 1.3, and 2.0 mM for fructose 6-phosphate, Mg.ATP, ATP and AMP,
      respectively. However, the addition of a protein crowding agent,
      poly(ethylene)glycol, greatly enhanced PFK binding to myofibrils, particularly at
      high pH (8.0) or high [KCl]. The studies suggest that reversible binding of PFK
      to myofibrils may be an important factor in the control of anaerobic glycolysis
      in vivo, especially under the cellular conditions of burst swimming exercise.

PMID- 7627130
TI  - The use of FAB mass spectrometry and pyroglutamate aminopeptidase digestion for
      the structure determination of pyroglutamate in modified peptides.
AB  - A new method for the determination of the modified amino acid structures of
      peptides containing pyroglutamyl residue in their N-terminal position is
      reported. The combination of fast atom bombardment (FAB) mass spectrometry and
      pyroglutamate aminopeptidase digestion provides a convenient and sensitive method
      for the identification of pyroglutamate. In order to investigate the nature of
      the amino terminal region of the follow post-translationally modified peptides
      containing pyroglutamyl residues, Neurotensin, Hypertrehalosaemic neuropeptide,
      and Luteinizing Hormone Releasing Hormone (LH-RH) were digested with
      pyroglutamate aminopeptidase and analyzed by FAB mass spectrometry. The method
      provided direct information about the N-terminal structure. The N-terminal
      pyroglutamates of these peptides are unequivocally determined at a level of 0.9
      2.8 nmol per peptide. Several of the complicated procedures and controversies,
      which accompany the application of traditional methods, are eliminated. We
      describe the advantages of the combination procedure of FAB mass spectrometry and
      pyroglutamate aminopeptidase digestion for modified amino acid determination.

PMID- 7627131
TI  - Polygalacturonase produced in apple tissue decayed by Botrytis cinerea.
AB  - An exo-polygalacturonase with an isoelectric point of 4.6 and an apparent
      molecular weight of 45 kDa was isolated from apple tissue decayed by Botrytis
      cinerea. This isozyme had a similar isoelectric point, optimum pH, and mode of
      action as an isozyme produced in liquid culture by B. cinerea. The enzyme
      produced in the decayed tissue was less sensitive to lower pH and less inhibited
      by CaCl2, MgCl2, or NaCl than the enzyme produced in culture. Such changes in the
      properties of the enzyme produced in infected tissue could have been essential
      for the pathogen's successful colonization of the host tissue. Among the cations
      studied, calcium was the best inhibitor of PG activity.

PMID- 7627132
TI  - New concept of energy migration and trapping in purple bacteria. Charge transfer
      polaron model.
AB  - A new hypothetical concept of the reaction center (RC) and the core BChl antenna
      is developed which claims to fit all up to date experimental data. In particular,
      the concept accounts for a number of findings still waiting for an explanation:
      a) the "red" shifts of the core BChl absorption peaks relative to those in their
      corresponding core BChls; b) the reason why in purple bacteria the second P2-P800
      BPH-Q brunch of RC is inactive c) recent data parallel 1,2 on a small excitation
      portion which escapes from the excited RC special pair back to antenna BChls; d)
      why the primary electron donor is not monomer but a pair of parallel B Chls; e)
      the reason why the fluorescence spectra of the RC special pairs are enormously
      red-shifted relative to their absorption spectra.

PMID- 7627133
TI  - Expression of Carcinoscorpius rotundicauda factor C cDNA.
AB  - The cDNA encoding Factor C (FC) from the Singaporean horseshoe crab
      Carcinoscorpius rotundicauda has been studied for in vitro coupled transcription
      translation (TnT) under the T7 promoter. Two species of full length cDNA, CrFC26
      and CrFC21 which differ in length and nucleotide sequence at their 5'
      untranslated regions (UTR) were used in this study. Wild type CrFC26 with a long
      5' UTR containing multiple "false" ATGs failed to generate a translated product.
      With a more accessible ATG codon in CrFC21, the recombinant construct gave a high
      yield of FC when transcribed and translated in vitro. CrFC26 deletion mutants
      which lack the entire 5' UTR and portions of the putative leader peptide were
      translatable, albeit at lower efficiency as compared to CrFC21. In vitro and in
      vivo expression of truncated portions of the CrFC21-T7 gene 10 fusions have been
      compared. In vitro reactions yielded single gene products from each of the
      expression constructs whereas E. coli produced three major immunoreactive bands
      of FC.

PMID- 7627134
TI  - Modifications of functional and physico-chemical properties of rat ileal plasma
      membranes.
AB  - A membrane fraction enriched with plasma membranes was isolated from rat ileal
      brush-border cells before and after five-day starvation of the animals.
      Cholesterol/phospholipid ratio of the standard cell membranes decreased highly
      significantly (0.42 to 0.18), as did the microviscosity of the membranes
      determined by polarization of fluorescence (0.187 to 0.142). Concomitantly, the
      specific activity of Na,K-ATPase in the basolateral membranes significantly
      increased (59 to 83 mumol ATP hydrolyzed per mg protein per min).

PMID- 7627135
TI  - Dephosphorylation of the phosphorylated elongation factor-2 in the livers of
      calorie-restricted and freely-fed rats during ageing.
AB  - Slowing down of the rate of protein synthesis during ageing is accompanied by
      alterations in the amounts and activities of elongation factors, eEF-1 and eEF-2.
      Since the activity of eEF-2 is regulated by phosphorylation, we have determined
      the changes in the activities of eEF-2-specific phosphorylating and
      dephosphorylating enzymes during ageing. Previously, we have reported an age
      related increase in the activity of eEF-2 kinase (BBRC, 192, 1210, 1993). We have
      now compared the activities of a dephosphorylating enzyme protein phosphatase 2A
      (PP2A) in young and old liver extracts from freely-fed or calorie-restricted
      rats. The activity of PP2A remain unaltered during ageing. Furthermore, there was
      no change in the kinetics and extent of PP2A-dependent and PP2A-independent
      dephosphorylation of eEF-2 during ageing.

PMID- 7627136
TI  - High membrane fluidity is related to NaCl stress in Candida membranefaciens.
AB  - The effect of hypersaline stress on the lipid composition of the salt-tolerant
      yeast Candida membranefaciens was studied. Fatty acid analyses of the plasma
      membrane showed a growth phase- and dose-dependent increase in the level of
      linolenic acid (C18:3) in 1.35 M NaCl-stressed cells. Palmitoleic acid (C16:1)
      was completely undetectable at all phases of the life cycle. Changes in the
      levels of other fatty acids were insignificant. The degree of unsaturation of
      fatty acids in the plasma membranes was higher in presence of 1.35 M NaCl. The
      fluorescence polarisation value of DPH (1,6-diphenyl- 1,3,5-hexatriene) in the
      spheroplasts of the stressed cells was lower as compared to the control cells,
      indicating the fact that a higher membrane fluidity favours osmotic adaptation
      against NaCl stress. Among different phospholipids, levels of
      Phosphatidylinositol and Phosphatidylethanolamine were elevated in the salt
      adapted cells as compared to their controls. The levels of Phosphatidylcholine
      and cardiolipin did not change significantly in response to hypersaline stress.
      The study points out that hypersalinity signals affect the lipid composition
      which in turn affects the membrane fluidity of C. membranefaciens.

PMID- 7627137
TI  - The interaction between nucleoproteins and thyroid response element (TRE) during
      regenerating rat liver.
AB  - We examined the interaction of nucleoproteins with thyroid response element (TRE)
      by south-western method. The proteins that bound specifically to TRE were
      detected at apparent molecular weight about 30,000 and 15,000 - 10,000. After
      digestion of nucleoproteins blotted on PVDF membrane with Endoglycosidase H, the
      amounts of TRE that bound to the nucleoproteins were increased. These results
      show that carbohydrate moieties of nucleoproteins have an important role on the
      interaction of the nucleoproteins with TRE. T3 stimulated the binding of TRE to
      nucleoproteins. The amount of T3 binding to nucleoproteins was changed during
      liver regeneration. These results indicate that T3 changes the interaction of the
      nucleoproteins with TRE, so T3 serves as a transducing signal to modulate the
      gene regulating activity of TRE-binding nucleoproteins. Liver regeneration may be
      controlled by these modification of interaction of nucleoproteins with DNA.

PMID- 7627138
TI  - A GTP-binding protein modulates a Ca2+ pump present in reticulocyte endocytic
      vesicles.
AB  - Rat reticulocytes were used to prepare endocytic vesicles to study calcium fluxes
      across the endosomal membrane. We used 45Ca2+, and found that endocytic vesicles
      from reticulocytes present a Ca(2+)-ATPase that pumps Ca2+ into the lumen of
      vesicles. This activity was sensitive to vanadate and the calmodulin antagonists:
      trifluoperazine and calmidazolium. Western blot analysis using a monoclonal
      antibody evidenced that Ca(2+)-ATPase present in reticulocyte endocytic vesicles
      is probably the same as the erythrocyte Ca2+ pump. Ca2+ pump activity was shown
      to be partially inhibited by GTP gamma S. Moreover, mastoparan and benzalkonium
      chloride, both activators of heterotrimeric G proteins, were found to decrease
      45Ca2+ uptake by endocytic vesicles. These results suggest the involvement of a
      trimeric G protein in the modulation of Ca(2+)-ATPase.

PMID- 7627139
TI  - Expression and purification of active form of HIV-1 protease from E.coli.
AB  - We have subcloned an N-terminal extended protease gene of human immunodeficiency
      virus (HIV) type 1 that is encoded in the protease domain of the pol open reading
      frame into expression vector pGEX-KG. A relatively high level of expression of
      recombinant HIV-1 protease (PR) was achieved with isopropyl beta-D
      thiogalactoside (IPTG) induction and glucose supplement. An isolation method
      consisting of denaturation of protein and followed by refolding was developed for
      releasing this recombinant HIV-1 PR into the soluble phase since most of the
      expressed protease was initially present in insoluble inclusion bodies. High
      purity of this recombinant HIV-1 PR was obtained by sequential purification using
      Sephadex G-50 gel filtration and CM-23 cellulose cation exchange chromatography,
      yielding the protease more than 1 mg per liter culture. N-terminal amino acid
      sequence analysis showed that the recombinant HIV-1 PR underwent autocleavage
      from the fusion protein during expression. SDS-PAGE indicated that the molecular
      weight of this recombinant HIV-1 PR is 11 kDa. This recombinant HIV-1 PR showed
      proteolytic activity for the synthetic peptide substrates corresponding to the
      sequence at the Gag MA/CA and Pol p6*/PR junctions. The purified enzyme whose
      specific activity for the heptapeptide SQNYPIV was 848.7 nmol*min-1*mg protease-1
      also processed recombinant polyprotein Gag41 as its substrate.

PMID- 7627140
TI  - Effects of 3,3',5-triiodo-L-thyronine (L-T3) and T3 analogues on mitochondrial
      function.
AB  - The effects of L-T3 and several analogues on mitochondrial parameters were
      determined in hypothyroid rats. These parameters include the 24 hour hormone
      induced changes in the bc1 complex and in the inner membrane's proton
      permeability. L-T3, and all analogues except rT3, increased mitochondrial
      ubiquinone to euthyroid levels. L-T3, D-T3 and 3'IpT2 but not rT3, Triac,
      Triprop, or Dimit, altered the bypass respiration in the bc1 complex. L-T3, D-T3,
      Triac, 3'IpT2, and Triprop, but not rT3 or Dimit, increased the membrane's proton
      permeability. Actinomycin D did not prevent the increase in mitochondrial
      ubiquinone or the permeability change. The results show the selective
      thyromimetic properties of the analogues and that some of the mitochondrial
      changes do not require protein synthesis.

PMID- 7627141
TI  - Boronic acid adducts of technetium dioxime (BATO) complexes derived from
      quinuclidine benzilate (QNB) boronic acid stereoisomers: syntheses and studies of
      their binding to the muscarinic acetylcholine receptor.
AB  - We have investigated the possibility of using BATO complexes derivatized with the
      muscarinic acetylcholine receptor (mAChR) antagonist, quinuclidinyl benzilate
      (QNB), for mAChR imaging. The BATO complexes, TcCl(DMG)3B-QNB, were prepared
      using QNB derivatives containing a 4'-boronic acid substituent on one of the
      benzilic benzene rings (QNB-boronic acid). The QNB-boronic acid molecule has two
      chiral centers, and all four QNB-BATO stereoisomers were made and evaluated. When
      studied using in vitro receptor binding assays based on tissue from rat brain
      caudate-putamen (which contains primarily M1 and M4 mAChR) and rat heart (M2
      mAChR), the QNB-boronic acid stereoisomers had binding affinities (KA) in the
      range 2 x 10(5)-1 x 10(8), at least 10-fold lower than the KA for QNB (ca 2 x
      10(9)). The stereochemistry of both centers had some influence on the affinity
      constant. When the TcCl(DMG)3B-QNB complexes were studied, none of the
      stereoisomeric complexes displayed measurable specific binding (KA < 10(6)), but
      all showed high non-specific binding. In vitro autoradiography with rat brain
      slices confirmed the absence of specific binding in these tracers. In vivo, the
      99mTcCl(DMG)3B-QNB complexes displayed minimal brain uptake, and modest heart
      uptake; the latter was unlikely to be related to uptake by the mAChR. In light of
      these findings, we conclude that the interaction between the TcCl(DMG)3B-QNB
      complexes and biological membranes is dominated by the hydrophobicity of the BATO
      moiety. The TcCl(DMG)3B-QNB complexes, therefore, have little potential for mAChR
      imaging.

PMID- 7627142
TI  - Fluorinated benzamide neuroleptics--III. Development of (S)-N-[(1-allyl-2
      pyrrolidinyl)methyl]-5-(3-[18F]fluoropropyl)-2, 3-dimethoxybenzamide as an
      improved dopamine D-2 receptor tracer.
AB  - We have prepared five new analogs (n-propyl, iso-propyl, allyl, n-butyl, and iso
      butyl) of the dopamine D-2 receptor antagonist, FPMB which result from
      modifications of the ethyl group at the pyrrolidine nitrogen in FPMB. As
      expected, all new derivatives showed higher apparent lipophilicity (log kw), with
      iso-butyl being the most lipophilic (log kw = 2.52), followed by the allyl
      derivative (log kw = 2.43). The allyl group showed the largest increase in
      affinity (from 0.26 nM for the ethyl substituent to 0.03 nM for the allyl
      substituent, almost 10-fold), followed by the n-propyl substituent which showed
      approximately five-fold better affinity than did the ethyl substituent.
      Radiosynthesis of (S)-N-[(1-allyl-2-pyrrolidinyl)methyl]-5-(3-[18F]fluoropropyl)
      2, 3-dimethoxybenzamide ([18F]fallypride) was carried out by nucleophilic
      substitution reaction of (S)-N-[(1-allyl-2-pyrrolidinyl) methyl]-5-(3
      tosyloxypropyl)-2,3-dimethoxybenzamide with no carrier added 18F-.
      [18F]Fallypride was obtained in approximately 20-40% yields (EOS/EOB, decay
      corrected) in specific activities of 900-1700 Ci/mmol after reverse phase HPLC
      purification in 60 min from EOB. High striatal uptake (upto 2.5% injected dose/g)
      of [18F]fallypride in rats was observed with striatal/cerebellar ratios of 17,
      42, 63 and 122 at 30, 60, 90 and 120 min post-injection, respectively. PET
      experiments with [18F]fallypride in a cebus monkey showed a brain uptake of 0.10%
      injected dose/cc. In rhesus monkeys [18F]fallypride showed rapid specific uptake
      in the striata (0.04-0.06% injected dose/cc) with striata/cerebellum ratios of
      approx. 3.0 at 14 min, 5.0 at 35 min and 8 at 70 min post-injection. Specifically
      bound [18F]fallypride was displaced with haloperidol (1 mg/kg) with a half-life
      of 18 min in the rhesus monkey.

PMID- 7627143
TI  - Early detection of amphotericin B induced nephrotoxicity by 99mTc-DTPA: a useful
      test.
AB  - Amphotericin B (AMB) with a broad spectrum of antifungal activity is used for the
      treatment of life-threatening mycoses, especially in immunocomprised patients.
      Since measurements of the blood level of AMB and of creatinine do not provide
      early warning of AMB induced renal toxicity, we studied the effects of AMB on
      biodistribution of a glomerular agent, 99mTc-DTPA. In Swiss mice, the toxicity of
      AMB was studied at single intravenous doses of 0.5-3.5 mg/kg body weight. Dose
      dependent effects consisted of decreased blood clearance and urinary excretion.
      Recovery of function was shown in dose ranges corresponding to high level
      clinical schedules. Serum creatinine changes lagged behind the 99mTc-DTPA
      alterations. This suggests that AMB toxicity might be monitored by blood/urinary
      clearance of 99mTc-DTPA.

PMID- 7627144
TI  - Asymmetric radiosynthesis of alpha-[11C]methyl-L-tryptophan for PET studies.
AB  - Asymmetric radiosynthesis of alpha-[11C]methyl-L-tryptophan has been achieved
      using the enantioselective [11C]methylation of the enolate of either 8
      (phenylsulfonyl) or 8-acetyl substituted derivatives of dimethyl (2S.3aR, 8aS)
      (+)-hexahydropyrrolo[2,3-b]indole-1,2-dicarboxylate. Reaction of the enolates
      generated by treatment with LDA at -78 degrees C, with [11C]methyl iodide at -78
      degrees C gave in 5 min incorporation of the radiolabel of 86% for 8
      phenylsulfonyl derivative and 63% for 8-acetyl derivative. The
      hexahydropyrrolo[2,3-b]indoles were then decyclized to the fully protected alpha
      [11]methyl-L-tryptophan by treatment with trifluoroacetic acid. Removal of all
      the protecting groups, including the phenylsulfonyl, was achieved by reaction
      with 10 N NaOH at 210 degrees C in a sealed vial. Neutralization of the alkali
      with 10 N H2SO4 followed by purification by HPLC gave alpha-[11C]methyl-L
      tryptophan with an overall radiochemical yield of 20% (uncorrected for decay)
      relative to the amounts of [11C]CH3I from 8-phenylsulfonyl derivative, and 9%
      (relative to [11C]CH3I; uncorrected for decay) from 8-acetyl derivative in a
      preparation time of 40 min after [11C]methyl iodide was introduced into the
      reaction mixture.

PMID- 7627145
TI  - Amino acid transport after transient global ischemia in rats: quantitative
      autoradiographic study using 3-[125I]iodo-alpha-methyl-L-tyrosine.
AB  - We studied the influence of reperfusion on amino acid transport of the brain
      after transient global ischemia in rats. The animals were subjected to 30-min
      four-vessel occlusion according to the procedures developed by Pulsinelli prior
      to recirculation for 3, 6, 24, 48 and 72 h. We used 3-[125I]iodo-alpha-methyl-L
      tyrosine as an autoradiographic tracer for selective cerebral amino acid
      transport maker. Following 30-min global ischemia, uptakes of 3-[125I]iodo-alpha
      methyl-L-tyrosine were significantly (P < 0.05) lower in substantia nigra,
      striatum and ventral tegmental area (6, 24, 48 and 72 h post-reperfusion), but
      significantly (P < 0.05) higher in cortex and thalamus (3 and 6 h post
      reperfusion). The influence of transient global ischemia on cerebral amino acid
      transport manifested region-specific three different patterns; namely,
      suppression, acceleration and no change in amino acid transport. The influence of
      transient ischemia on catecholamine-synthesizing brain sites is most remarkable.

PMID- 7627146
TI  - Synthesis and biodistribution of nitrido technetium-99m radiopharmaceuticals with
      dithiophosphinate ligands: a class of brain imaging agents.
AB  - The symmetrical complexes [99mTc][TcN(R2PS2)2] [R = CH3, CH2CH3, CH2CH2CH3,
      CH2(CH3)2], and the unsymmetrical complex [99mTc][TcN(Me2PS2)(Et2PS2)] have been
      prepared, at tracer level, through a two-step procedure involving the preliminary
      formation of a prereduced technetium nitrido intermediate followed by
      substitution reaction onto this species by the appropriate dithiophosphinate
      ligand [R2PS2]Na. The chemical identity of the resulting complexes have been
      established by comparison with the corresponding 99Tc-analogs prepared, at
      macroscopic level, by reacting the complex [99TcNCl4] [n-Bu4N] (n-Bu = n-butyl)
      with an excess of ligand in methanol, and characterized by elemental analyses and
      spectroscopic techniques. The complexes are neutral and lipophilic, and possess a
      square pyramidal geometry, with an apical Tc identical to N group and two
      dithiophosphinate ligands spanning the four positions on the basal plane through
      the four sulfur atoms of the > PS2 group. In vitro studies showed that these
      radiopharmaceuticals are stable in solution and that their chemical identity was
      not altered after incubation with rat blood. Biodistribution studies have been
      carried out in rats and primates. The results demonstrate that these compounds
      are significantly retained into the brain of these animals for a prolonged time.
      Planar gamma camera images have been obtained in monkeys showing a good
      visualization of the cerebral region. However, the existence of persistent blood
      activity yields a brain/blood ratio lower than that observed with other 99mTc
      based brain perfusion imaging agents.

PMID- 7627147
TI  - Comparative PET studies of the distribution of (-)-3,4-methylenedioxy-N
      [11C]methamphetamine and (-)-[11C]methamphetamine in a monkey brain.
AB  - Carbon-11 labeled (-)-methamphetamine and (-)-3,4-methylenedioxy-N
      methamphetamine were synthesized by methylation of the corresponding desmethyl
      precursors with [11C]H3I in 40-60% yield in a synthesis time of 30 min from EOB
      with a specific activity of 0.5-1.2 Ci/microM. PET studies in a Rhesus monkey
      revealed that the uptakes of both compounds in different brain regions were
      similar, and the retention of radioactivity in these brain regions remained
      constant throughout the study for the former while it was washed out slowly for
      the latter. The half-life of (-)-3,4-methylenedioxy-N-methamphetamine in monkey
      brain was approximately 70 min. Analyses of arterial plasma by HPLC revealed that
      50% of radioactivity in the plasma remained as (-)-methamphetamine while only 3%
      remained as (-)-3,4-methylenedioxy-N-methamphetamine at 60 min post-injection.
      These results suggest that the uptakes of both compounds in monkey brain are
      probably not receptor mediated. Rather, blood flow, lipophilicity of the
      compounds or other transport mechanisms may play a role in their uptakes.

PMID- 7627148
TI  - Complexes of technetium-99m with tetrapeptides, a new class of 99mTc-labelled
      agents.
AB  - Tetrapeptides are a class of N4-tetraligands that can efficiently bind 99mTc. In
      fact, tetrapeptides can be considered as derivatives of mercaptoacetyltriglycine
      (MAG3) in which the mercaptoacetyl moiety is replaced by a more stable and easier
      to handle aminoacyl group. Direct labelling of tetrapeptides with 99mTc in
      alkaline medium (pH > or = 11) in the presence of stannous ions gave a high yield
      (> 95%) of one or two (probably isomeric) radiochemical species. Exchange
      labelling at different pH values in the presence of stannous tartrate resulted in
      lower yields of the same 99mTc-labelled products as those formed during direct
      labelling. In addition, other radiochemical species were formed of which one was
      characterized as an oxotechnetium-complex with the cyclisized tetrapeptide.
      Tetrapeptides with a chiral centre in the first amino acid yield upon labelling
      with 99mTc two radiochemical species, probably the two diastereomers with an
      oxotechnetium core respectively syn and anti with respect to the substituent on
      the amino acid. Only one diastereomer was observed when the chiral carbon atom is
      located in the second or third amino acid. Electrophoresis indicated that these
      new 99mTc-labelled complexes are neutral in acidic medium and negatively charged
      in neutral and alkaline conditions. This correlates with a complex in which an
      oxotechnetium(V) group is bound to the ligand through three deprotonated nitrogen
      atoms of the amide functions and the free electron pair of the amine nitrogen
      atom. Biodistribution in mice showed for all studied 99mTc-labelled tetrapeptides
      a rapid clearance from the blood mainly by the renal system. The presence of a
      methyl substituent in the tetrapeptide increased the urinary excretion. 99mTc
      labelled L-glycylalanylglycylglycine showed in mice a urinary excretion
      comparable to that of 99mTc-MAG3. Further rise of lipophilicity by introduction
      of a dimethyl, isopropyl or isobutyryl group leads to increased hepatobiliary
      handling. It is concluded that tetrapeptides are an interesting group of
      technetium complexing agents which can easily be labelled with 99mTc at room
      temperature in alkaline medium. This class offers the possibility of a wide
      variety of derivatives, just by substituting one or more amino acids. This group
      of ligands thus opens a new research field of 99mTc-complexes with potential
      usefulness in several areas.

PMID- 7627149
TI  - Investigation of the labelling characteristics of 99mTc-mercaptoacetyltriglycine.
AB  - S-Benzyl-, S-benzamidomethyl- and S-benzoylmercaptoacetyltriglycine were
      synthesized and compared in exchange labelling experiments for the preparation of
      99mTc-MAG3. The rate of exchange from 99mTc-tartrate to 99mTc-MAG3 starting from
      the respective precursors was determined in different conditions. Labelling
      proceeded most rapidly starting from the S-benzoyl protected precursor but
      efficient labelling was also accomplished using the more stable S-benzamidomethyl
      and S-benzylmercaptoacetyltriglycine. 99mTc-MAG3 was also prepared by direct
      labelling of unprotected mercaptoacetyltriglycine at alkaline pH. Radiochemical
      purity in these conditions is mainly dependent on the pH during labelling.

PMID- 7627150
TI  - 65Zn uptake by liver of rats fed 3'-methyl-dimethylaminoazobenzene.
AB  - The uptake of 65Zn, determined by gamma-counting and also by autoradiography,
      significantly increased with the increasing level of metallothionein in liver 4
      weeks after the start of feeding a diet containing 3'-methyl
      dimethylaminoazobenzene (3'-Me-DAB), at which time the serum gamma-glutamyl
      transpeptidase activity was not yet significantly elevated. At this time,
      furthermore, hepatic uptake of 67Ga-citrate did not increase and that of 99mTc-Sn
      colloid decreased in 3'-Me-DAB-fed rats. These results suggest that a short-life
      gamma-emitting isotope such as 69mZn may be useful for the detection at the early
      stage of hepatic carcinogenesis.

PMID- 7627151
TI  - Lymphoscintigraphy via the targeting of macrophages with 99mTc-J001X poly
      galactoside in a model of pyogranulomas developed in sheep lymph nodes.
AB  - Lymphoscintigraphy usually involves labeled microparticles or colloids that
      distribute in the lymph flow. A new strategy for imaging pathological lymph nodes
      would be the targeting of macrophages recruited in these lesions. The potential
      for lymphoscintigraphy of the highly diffusible J001X acylated polygalactoside
      labeled with 99mTc was studied and compared to usual colloidal agents in a model
      of infectious granulomas developed in sheep. Scintigraphic and histological
      assessment of the specificity of targeting was performed using a MAb (OM1) raised
      against ovine macrophages taken as reference. This study has evidenced the
      ability of J001X specifically to image pathologic lymph nodes and more especially
      the second lymph node in the same chain with a significant scintigraphic
      contrast.

PMID- 7627152
TI  - 99mTc direct labeling of anti-CEA monoclonal antibodies: quality control and
      preclinical studies.
AB  - The anti-carcinoembryonic B2C114 monoclonal antibody was radiolabeled with 99mTc
      by a direct method and quality control tested in vitro by instant thin layer
      chromatography, gel column scanning and cellulose acetate electrophoresis and
      assessed in vivo for radioimmunodetection on a murine spontaneous mammary
      carcinoma. The optimal results of percent 99mTc bound to protein were obtained at
      a dithiothreitol:antibody molar ratio ranging from 800:1 to 1000:1 and at a
      methylene diphosphonate:stannous fluoride weight ratio of 4.3:1. Although
      cysteine removed up to 18% of the label during the first 4 h, the stability of
      the tracer appeared to be excellent in human serum at 37 degrees C and when
      challenged with DTPA. 99mTc-labeled B2C114 demonstrated good and specific in vivo
      tumor targeting.

PMID- 7627153
TI  - A comparative cerebral blood flow study in a baboon model with acetazolamide
      provocation: 99mTc-HMPAO vs 123I(IMP).
AB  - Pharmacological interactions are important when nuclear medical procedures are
      applied to patients under drug therapy, or drug provocation. This study compares
      in baboon models (regional) cerebral blood flow [(r)CBF] results from 99mTc-HMPAO
      and 123I-iodoamphetamine [123I(IMP)] each with and without acetazolamide, the
      latter a suggested drug for testing cerebrovascular reserve. Expected differences
      in cerebral uptake were observed between the two radio-tracers without
      acetazolamide. The increase in tracer uptake resulting from acetazolamide is
      significantly enhanced for 123I(IMP), which could have diagnostic implications.

PMID- 7627154
TI  - Lipiodol uptake and retention by human hepatoma cells.
AB  - Lipodol has important diagnostic and therapeutic uses in hepatoma. However, the
      mechanisms of its selective, prolonged retention in hepatoma cells is not well
      understood. Therefore, using oil-red O, light and electron microscopy and neutron
      activation analysis we have determined that HepG2 cells are characterized by
      lipiodol deposition and emulsification on the cell surface, action uptake of
      lipodol by endocytosis, and prolonged intracellular retention. These findings may
      have major clinical significance in the development of a new treatment for
      hepatoma patients.

PMID- 7627155
TI  - A rapid, single vessel method for preparation of clinical grade ligand conjugated
      monoclonal antibodies.
AB  - A rapid, single vessel method for the preparation of clinical grade chelate
      conjugated monoclonal antibodies has been developed. By use of an Amicon
      concentrator with reservoir, each of the steps necessary for the preparation of
      the conjugated drug may be performed in a single vessel. Advantages include
      reduced risk of metal, pyrogen and bacterial contamination; buffer exchanges are
      achieved rapidly and efficiently using a continuous dilution method. The
      radiolabeling efficiency, the radiochemical purity, the total immunoreactivity
      and the affinity of the final product have been evaluated in the production of
      CHXA-DTPA-chelate conjugated HuM195. The characteristics compare favorably to
      those achieved using our conventional synthetic methods.

PMID- 7627156
TI  - Lateral neck imaging for spatial localization of parathyroid tissue.
AB  - Two patients with an ectopic parathyroid adenoma are described. In both cases the
      lesions were clearly demonstrated in an anterior view on T1-201/Tc-99m
      scintigraphy, but were not identified during the first surgical exploration.
      Failure to identify the ectopic adenoma at surgery in the second patient led to
      oblique and lateral views being obtained. These views permitted correct depth
      localization. We, therefore, believe that lateral and oblique views can be of
      assistance in improving preoperative localization of an ectopic parathyroid
      adenoma.

PMID- 7627157
TI  - Measures and pitfalls for successful preparation of "no carrier added" asymmetric
      6-[18F]fluor-L-dopa from 18F-fluoride ion.
AB  - 6-[18F]Fluoro-L-dopa (6FD) has been proposed and used for probing cerebral
      dopamine metabolism by positron emission tomography. Recently a new method for
      asymmetric synthesis of 6FD has been reported. This method involves synthesis of
      6-[18F]fluoro-3,4-dimethoxybenzylbromide which is reacted with (S)-1-Boc-2-tert
      butyl-3-methyl-4-imidazolidinone. The resulting alkylated compound is then
      hydrolyzed with hydriodic acid to produce 6FD. This method has been used to
      produce 6FD and several critical steps that required attention found, in addition
      to some modification for successful 6FD production. 6FD is prepared in 6-13%
      radiochemical yield (decay not corrected) after HPLC purification with a
      production time of 85 min.

PMID- 7627159
TI  - Don't get around much any more.

PMID- 7627158
TI  - Platelet radiolabelling with 111 Indium for in vivo studies: a methodological
      reappraisal.
AB  - Two ligands widely used for 111In labeling of human platelets, oxine and
      tropolone, were compared as to the degree of their influence on platelet
      function. The labelling efficiency was assessed as a function of experimental
      variables. A good preservation of platelet function as evaluated by ex vivo
      aggregation was obtained with both techniques. The extent of tracer detached from
      platelets was evaluated in vitro and in vivo: in normal subjects 111In was
      virtually all bound to platelets. A significant reduction in radiolabelling
      efficiency and a decreased percentage of 111In bound to platelets in vivo was
      observed in patients with platelet counts < 150,000/mL.

PMID- 7627160
TI  - Language of primary nursing.

PMID- 7627161
TI  - Hydrocolloid dressings.

PMID- 7627162
TI  - Epilepsy and the older person.

PMID- 7627163
TI  - Evaluated by non-nurses.

PMID- 7627164
TI  - Ageing in America.

PMID- 7627165
TI  - 'The huge feeling of guilt never leaves you'.

PMID- 7627166
TI  - Rather a daunting exercise in the care of elderly people.

PMID- 7627168
TI  - The 'golden age' of radio is now.

PMID- 7627167
TI  - Action plan for 1995-1996 in FOCUS.

PMID- 7627169
TI  - Linking past to present.

PMID- 7627170
TI  - Answer to an old problem?

PMID- 7627171
TI  - Long-term catheter use in the community.

PMID- 7627172
TI  - Diabetes mellitus in old age.

PMID- 7627173
TI  - Bittersweet area of care.

PMID- 7627174
TI  - Depression 'stops people functioning'.

PMID- 7627175
TI  - Dressing down the health department.

PMID- 7627176
TI  - Nursing homes are for nursing people.

PMID- 7627178
TI  - Willful 'white lions'.

PMID- 7627177
TI  - Precious time.

PMID- 7627179
TI  - The living room.

PMID- 7627180
TI  - Molecular basis of dihydropteridine reductase deficiency.
AB  - The spectrum of mutations causing dihydropteridine reductase is reviewed. A total
      of 12 point mutations have been described that map in the DHPR cDNA, resulting in
      amino acid substitutions, insertions and premature terminations. A further two
      mutations are described which result in aberrant splicing of DHPR transcripts.
      The application of the mutation identification to diagnostics and clinical
      treatment is discussed.

PMID- 7627181
TI  - Mutations in the Norrie disease gene.
AB  - We report our experience to date in mutation identification in the Norrie disease
      (ND) gene. We carried out mutational analysis in 26 kindreds in an attempt to
      identify regions presumed critical to protein function and potentially correlated
      with generation of the disease phenotype. All coding exons, as well as noncoding
      regions of exons 1 and 2, 636 nucleotides in the noncoding region of exon 3, and
      197 nucleotides of 5' flanking sequence, were analyzed for single-strand
      conformation polymorphisms (SSCP) by polymerase chain reaction (PCR)
      amplification of genomic DNA. DNA fragments that showed altered SSCP band
      mobilities were sequenced to locate the specific mutations. In addition to three
      previously described submicroscopic deletions encompassing the entire ND gene, we
      have now identified 6 intragenic deletions, 8 missense (seven point mutations,
      one 9-bp deletion), 6 nonsense (three point mutations, three single bp
      deletions/frameshift) and one 10-bp insertion, creating an expanded repeat in the
      5' noncoding region of exon 1. Thus, mutations have been identified in a total of
      24 of 26 (92%) of the kindreds we have studied to date. With the exception of two
      different mutations, each found in two apparently unrelated kindreds, these
      mutations are unique and expand the genotype database. Localization of the
      majority of point mutations at or near cysteine residues, potentially critical in
      protein tertiary structure, supports a previous protein model for norrin as
      member of a cystine knot growth factor family (Meitinger et al., 1993). Genotype
      phenotype correlations were not evident with the limited clinical data available,
      except in the cases of larger submicroscopic deletions associated with a more
      severe neurologic syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7627182
TI  - Mutations and polymorphisms in the human ornithine transcarbamylase gene:
      mutation update addendum.
AB  - This mutation update addendum summarizes 30 new mutations and polymorphisms found
      in the ornithine transcarbamylase (OTC) gene since the publication in this
      journal of the first mutation update. Thus, more than 60 mutations and
      polymorphisms in the OTC gene are currently known. Most of the mutations have
      been seen in a single family and the few recurrent mutations occurred in CpG
      dinucleotides. The presumed deleterious effects of most mutations await
      confirmation by appropriate expression studies. Once the tertiary structure of
      the enzyme is fully known, and the functional domains established, the effects of
      mutations, or lack thereof, could be better predicted.

PMID- 7627183
TI  - Characterization of germline mutations of the gene encoding Bruton's tyrosine
      kinase in families with X-linked agammaglobulinemia.
AB  - Bruton's tyrosine kinase (Btk) has been identified as the protein responsible for
      the primary immunodeficiency X-linked agammaglobulinemia (XLA) and has been
      described as a new member of Src-related cytoplasmic protein tyrosine kinases. We
      have recently characterized the structure of the entire gene encoding Btk and
      developed a polymerase chain reaction (PCR)-based assay to detect germline
      mutations within it. In this report we describe six mutations, five of which are
      novel, of the Btk gene in patients with XLA and demonstrate the inheritance
      pattern of the defect within the families of the affected individuals. The
      mutations found include two nonsense and two missense mutations, a single base
      deletion at an intron acceptor splice site, and a 16-bp insertion. A single
      strand conformation polymorphism was also found in the 5' end of intron 8 with
      the same assay. This technique has provided a powerful tool for direct analysis
      of the Btk gene for the diagnosis of XLA and carrier detection. The
      identification of new mutations may eventually reveal the role of Btk in the
      signaling pathways involved in B-cell development.

PMID- 7627184
TI  - Gaucher disease in Spanish patients: analysis of eight mutations.
AB  - Gaucher disease is particularly prevalent among Ashkenazi Jews; thus most studies
      have been reported on this ethnic group. We present the first data on Spanish
      patients with Gaucher disease and provide one of the first reports on a fairly
      well defined, large, non-Jewish population. Eight mutations were analyzed in 35
      patients, with different clinical subtypes, by restriction enzyme digestion or
      allele-specific oligonucleotide (ASO) hybridization, after PCR amplification of
      genomic DNA. Analysis of the eight mutations allowed identification of 77.2% of
      the disease alleles, N370S and L444P alone accounting for 70%. Mutation N370S,
      carried by 31 alleles (44.3%), appeared to be the most prevalent in the Spanish
      population. The frequency of this mutation and of the N370S/N370S genotype is
      closer to those described for Ashkenazi Jews than to the frequencies found in
      other non-Jewish populations. Mutation L444P, the second most abundant mutation,
      occurred in 25.7% of the disease alleles. Four alleles carrying mutation D409H
      (5.7%) were detected in patients of different clinical expression and one RecNciI
      allele in a type I patient. Mutations 84GG, IVS2 + 1, R463C, and RecTL were also
      screened but were not found in any of our patients.

PMID- 7627185
TI  - African, Native American, and European mitochondrial DNAs in Cubans from Pinar
      del Rio Province and implications for the recent epidemic neuropathy in Cuba.
      Cuba Neuropathy Field Investigation Team.
AB  - Genetic predisposition, particularly specific mitochondrial DNA (mtDNA)
      backgrounds, has been proposed as a contributing factor in the expression of an
      epidemic of bilateral optic neuropathy that has affected residents of Cuba since
      1991. To substantiate or refute the possibility that specific subsets of mtDNAs
      could participate in disease expression, we took advantage of the heterogeneous
      ethnic origin of the Cuban population and the recent identification of a number
      of mtDNA polymorphisms that appear to be specific for Africans, Native Americans,
      and Europeans. The screening of both carefully selected people with epidemic
      neuropathy and control subjects from the Pinar del Rio Province for these
      polymorphisms revealed that African, Native American, and European mtDNA
      haplotypes were equally represented among case and control subjects, and
      suggested that approximately 50% of Cuban mtDNAs originated from Europeans, 46%
      from Africans, and 4% from Native Americans. These findings demonstrate that
      mutations arising in specific mtDNAs are unlikely to play a role in the epidemic
      neuropathy and indicate that analysis of mtDNA haplotypes can be a valuable tool
      for assessing the relative maternal contribution of Africans, Native Americans,
      and Europeans in a mixed population.

PMID- 7627186
TI  - Identification of a novel mutation causing aspartylglucosaminuria reveals a
      mutation hotspot region in the aspartylglucosaminidase gene.
AB  - Aspartylglucosaminuria (AGU) is a recessively inherited metabolic disorder caused
      by the deficiency of a lysosomal enzyme, aspartylglucosaminidase. The worldwide
      most common mutation causing the disease is the AGUFin, enriched in Finland; all
      the other known AGU mutations are family-specific. We developed exon-specific
      primers to facilitate mutation search directly from the genomic DNA and
      identified a novel mutation, designated AGUFin minor, in seven Finnish AGUFin
      compound heterozygote patients. This deletion/frameshift mutation creates a
      premature translational termination codon and was shown to result in severely
      reduced transcript levels as quantified by the solid-phase minisequenching
      method. Genealogical data on this novel mutation suggest its relatively recent
      introduction into the population. The AGU mutations identified so far have been
      reported to be evenly distributed throughout the 1 kb coding region of the AGA
      cDNA. We identified a mutation hotspot region of 40 bp within the 12.5 kb AGA
      gene containing two previously identified mutations and the novel AGUFin minor
      mutation characterized in this study.

PMID- 7627187
TI  - Analysis of beta-thalassemia mutations in the United Arab Emirates provides
      evidence for recurrent origin of the IVSI nt 5 (G-C) mutation.
AB  - Beta-thalassemia mutations were characterized in a sample of 70 patients from
      United Arab Emirates (U.A.E.), resulting in an enlargement of the spectrum of
      types found in the country. The complete association between the most common IVS
      I nt 5 (G-C) mutation and a specific haplotype reveals an independent origin of
      this mutation in U.A.E.

PMID- 7627188
TI  - Somatic mutations in VNTR-locus D1S7 in human colorectal carcinomas are
      associated with microsatellite instability.
AB  - To elucidate mutation mechanisms in hypervariable VNTR loci, we have studied
      somatic mutation events with the minisatellite probe MS1 (VNTR locus D1S7) in 224
      colorectal carcinomas (CRC). The D1S7 locus consists of a 9-basepair (bp) repeat
      unit. The copy number varies from about 100 to 2000, and the germline mutation
      rate is high. Here we demonstrate a high D1S7 somatic mutation rate in CRC
      (37/224), higher than indicated earlier by others. We also demonstrate that the
      most frequent mutational event by far (n = 34) involves small reductions in VNTR
      fragment size (median loss 22 repeat units, range 2-154), furthermore, in one
      half of these cases, this event is biallelic. We wanted to test whether these
      somatic mutations mirror the same genetic instability as seen by RER (replication
      error), a phenomenon recently described in tumour DNA from both sporadic and
      familial cases of CRC. All blood/tumour DNA pairs displaying MS1 mutation (n =
      37) as well as 37 randomly selected pairs without MS1 mutation were tested with
      four tetranucleotide short tandem repeats (STRs, microsatellites). There is a
      strong association between mutations at the D1S7 locus and the occurrence of new
      STR alleles (P < 0.001). This is the first report of the existence of a
      minisatellite as a marker for genetic instability/RER in colorectal carcinomas.
      The findings may also cast light upon the mechanism for somatic mutations in this
      minisatellite.

PMID- 7627189
TI  - A 31-mutation assay for cystic fibrosis testing in the clinical molecular
      diagnostics laboratory.
AB  - We devised a set of allele-specific probes to detect simultaneously 31 known
      cystic fibrosis mutations using PCR and the reverse dot blot detection format.
      The assay has been implemented in a clinical setting to the screening of over 750
      individuals. Of these 102 Caucasians, 20 Hispanics and 1 Indian patient were
      affected with cystic fibrosis. The mutation detection rate in the 204 Caucasian
      and 40 Hispanic CF chromosomes was respectively, 88% and 85%. The availability of
      the probe sequences to CF screening laboratories should allow implementation of
      this assay in a clinical setting and comparison of its mutation typing rate among
      different centers.

PMID- 7627190
TI  - Protein 4.1 Lille, a novel mutation in the downstream initiation codon of protein
      4.1 gene associated with heterozygous 4,1(-) hereditary elliptocytosis.

PMID- 7627191
TI  - Identification of a new missense mutation in exon 2 of the human hypoxanthine
      phosphoribosyltransferase gene (HPRTIsar): a further example of clinical
      heterogeneity in HPRT deficiencies.

PMID- 7627192
TI  - Identification of a new mutation (P178S) in an African-American patient with type
      2 Gaucher disease.

PMID- 7627193
TI  - Carbonic anhydrase II deficiency in a Japanese patient produced by a nonsense
      mutation (TAT-->TAG) at Tyr-40 in exon 2, (Y40X).

PMID- 7627194
TI  - Spectrum of beta-thalassemia mutations in the Gaza area.

PMID- 7627195
TI  - A 13-bp deletion (1952 del 13) in the methylmalonyl CoA mutase gene of an
      affected patient.

PMID- 7627196
TI  - Screening for mutations in factor VIII gene using the single-strand conformation
      polymorphism.

PMID- 7627197
TI  - Folliculostatins, gonadotropins and a model for control of growth in the grey
      fleshfly, Neobellieria (sarcophaga) bullata.
AB  - The sequences of two folliculostatic peptides of the fleshfly Neobellieria
      bullata have been determined recently. The first peptide (Neb-TMOF: H-NPTNLH-OH),
      originates from a 75 kDa precursor protein found in vitellogenic oocytes. The
      hexapeptide directly inhibits the synthesis of trypsin-like enzymes in the gut,
      and thus lowers the concentration of yolk polypeptides in the hemolymph. It also
      inhibits the biosynthesis of ecdysone in the larval ring gland. Therefore, it
      could also be named prothoracicostatic hormone (Neb-PTSH). The second peptide
      (Neb-colloostatin: H-SIV-PLGLPVPIGPIVVGPR-OH) acts on previtellogenic follicles
      and is a cleaved product of a collagen-like precursor molecule. Our results
      indicate that peptides that are cleaved from matrix proteins could act as growth
      inhibiting factors. Gonadotropin releasing hormone (GnRH)-immunolike peptides
      were not identified, but progress is being made in the isolation and
      characterization of factors which stimulate cAMP production by the ovary. Using
      these results, a novel model of growth control in which matrix proteins play an
      important role as a potential source of growth regulators has been developed.

PMID- 7627198
TI  - Biosynthesis and Catabolism of Insect Hormones and Pheromones. Proceedings of a
      conference of the American Chemical Society. San Diego, California, 13-14 March
      1994.

PMID- 7627199
TI  - Parasitism-induced accumulation of FMRFamide-like peptides in the gut innervation
      and endocrine cells of Manduca sexta.
AB  - Manduca sexta larvae that are parasitized by the braconid wasp Cotesia congregata
      enter a state of developmental arrest following emergence of the wasp larvae from
      the host. These fifth instar hosts linger for 2 to 3 weeks without resuming
      feeding, molting, or metamorphosis once the wasps emerge. Immunohistochemical
      staining with antiserum against FMRFamide revealed dramatic accumulation of
      FMRFamide-like peptide(s) in the gut nervous and endocrine systems of the
      developmentally arrested larvae when compared to that observed in unparasitized
      feeding or starved larvae. Specifically, the number of immunopositive cells and
      the intensity of staining was enhanced in the neurons of the frontal ganglion,
      the axons and axon terminals on the midgut surface, and in the gastric endocrine
      cells. These results were confirmed using ELISA to show that the relative amounts
      of FMRFamide-like peptides in midgut extracts were highly elevated in the
      parasitized larvae relative to the fed or starved unparasitized larvae. These
      data suggest that FMRFamide-like peptides in developmentally arrested larvae are
      produced in a significantly larger number of gastric endocrine cells, and that
      the rate of release of the peptides may be suppressed, or the rate of their
      synthesis may be elevated. Localization of FMRFamide-like peptides in the gastric
      endocrine cells of C. congregata is also described.

PMID- 7627200
TI  - Stereospecific, mechanism-based, suicide inhibition of a cytochrome P450 involved
      in ecdysteroid biosynthesis in the prothoracic glands of Manduca sexta.
AB  - The first required step in ecdysteroid (molting hormone) biosynthesis, dietary
      cholesterol (C) conversion to 7-dehydrocholesterol (7dC) via 7,8-dehydrogenation,
      is mediated by a microsomal cytochrome-P450 monooxygenase specific to the larval
      prothoracic gland. A subsequent series of unknown "black-box" oxidations of 7dC
      result in the unusual ring geometry (cis-A/B) and functionality (6-keto-7-ene-14
      alpha-ol) of the ecdysteroids and has been thought to involve the initial
      formation of alpha-5,6-epoxy-7-dehydrocholesterol (alpha epo7dC). Pharmacological
      studies indicated that conversion of C to 7dC in prothoracic gland homogenates
      was strongly and equally inhibited by the isomeric cholesterol substrate
      analogues alpha- and beta-5,6-epoxycholesterol (alpha- and beta epoC) and alpha-
      and beta-5,6-iminocholesterol (alpha- and beta iminoC). With respect to the
      conversion of C to ecdysteroids by disrupted glands, however, the two alpha
      isomeric substrates were 10-fold more inhibitory than were their beta-analogues.
      Indeed, alpha amino C was as active as the non-specific pyrimidyl cytochrome-P450
      monooxygenase inhibitor fenarimol that shows moderate toxicity in many insect
      species. All four cholesterol analogues competitively inhibited cholesterol 7,8
      dehydrogenation, but only alpha epoC and possibly alpha iminoC were desaturated
      to delta 7-products. Although the KmS (and KiS) for all the substrates were
      similar (1.7-6.0 x 10(-5) M), the Vmax for alpha epoC dehydrogenation was eight
      fold higher than that of C, making it a superior substrate for following this
      reaction in ecdysteroidogenic tissues rich in endogenous C. The 7,8
      dehydrogenation of alpha epoC and alpha iminoC by prothoracic glands would
      produce the potentially reactive intermediates, alpha epo7dC and alpha imino7dC,
      respectively. They, in turn, could then undergo facile, acid-catalyzed ring
      opening to the allylic-stabilized carbo-cation electrophiles. These very
      reactive, transient species, if formed in the active site of the monooxygenase,
      would then alkylate either the heme group or the apoprotein of the cytochrome or
      both, leading to the irreversible inhibition of the enzyme. The present data show
      that alpha epoC and probably alpha iminoC are mechanism-based suicide inhibitors
      of the enzyme catalyzing cholesterol 7,8-dehydrogenation and may be the
      prototypes of a new class of selective insect control agents.

PMID- 7627201
TI  - Analysis of ecdysteroid action in Malacosoma disstria cells: cloning selected
      regions of E75- and MHR3-like genes.
AB  - IPRI-MD-66 (MD-66) cells respond to 20-hydroxyecdysone (20E, 4 x 10(-6) M) in the
      medium by producing cytoplasmic extensions, clumping and attaching themselves to
      the substrate. These morphological changes are at a maximum by 6 days post
      treatment. Degenerate oligonucleotides, designed on the basis of conserved amino
      acid sequences in the DNA and ligand binding regions of the members of the
      steroid hormone receptor superfamily, were used in RNA-PCR to isolate two cDNA
      fragments, Malacosoma disstria hormone receptor 2 (MdHR2) and Malacosoma disstria
      hormone receptor 3 (MdHR3) from the MD-66 cells. Comparison of deduced amino acid
      sequences of these cDNA fragments with the members of the steroid hormone
      receptor superfamily showed that MdHR2 is most closely related to E75 proteins of
      Manduca sexta, Galleria mellonella and Drosophila melanogaster. The MdHR3 is most
      closely related to Manduca hormone receptor 3 (MHR3), Galleria hormone receptor 3
      (GHR3) and Drosophila hormone receptor 3 (DHR3) proteins. At a concentration of 4
      x 10(-6) M, 20E induces the expression of MdHR2 and MdHR3 beginning at 3 h,
      reaching maximum levels in 12 h and declining in 24 h. MdHR2 binds to a 2.5 kb
      mRNA, whereas MdHR3 binds to a 4.5 kb mRNA. Based on sequence similarity, RNA
      size and ecdysone inducibility, we conclude that these cDNA fragments, cloned
      from MD-66 cells, are regions of E75- (MdHR2) and MHR3- (MdHR3) like genes.

PMID- 7627202
TI  - Ecdysteroid production in Drosophila melanogaster reared on defined diets.
AB  - Larvae of Drosophila melanogaster were reared aseptically on defined diets
      containing either cholesterol, campesterol or sitosterol as the only dietary
      sterol. Sterol analyses of pupae revealed that insects reared on campesterol and
      sitosterol diets contained 3.3 and 8.1% cholesterol, indicative of an ability to
      accumulate this sterol. Ecdysone and 20-hydroxyecdysone were the predominant
      ecdysteroids in insects from all diet studies, though makisterone A was detected
      in pupae reared on campesterol and sitosterol.

PMID- 7627204
TI  - The juvenile hormone receptor of the cockroach Leucophaea maderae.
AB  - The juvenile hormone (JH) receptor has been isolated and purified from fat bodies
      of females and males of Leucophaea maderae. The sequence of procedures that
      yielded an apparently pure compound involved ammonium sulfate precipitation (20
      60% saturation cut), DEAE anion exchange column chromatography, and
      polyacrylamide gel electrophoresis. The molecular size of the resulting high
      affinity JH-binding protein is about 64 kDa and is apparently composed of two
      equal subunits of 32 kDa. A polyclonal antibody has been produced against this
      molecule and used for the construction of an immunoaffinity column. A pure JH
      receptor molecule has been isolated from crude fat body homogenates with this
      affinity column. The JH receptor is first identified in last instar nymphs and
      quantitatively increases as the instar progresses towards adult development. In
      penultimate nymphal instars this JH receptor could not be identified and this is
      correlated with a lack of competence to make vitellogenin (Vg) upon exposure to
      the JH analog methoprene. Thus, a correlation is seen between the presence of the
      JH receptor and the competence to synthesize Vg.

PMID- 7627203
TI  - Photoaffinity labeling of methyl farnesoate epoxidase in cockroach corpora
      allata.
AB  - The last enzyme in the biosynthetic pathway to juvenile hormone III in the
      corpora allata of hemimetabolous insects is methyl farnesoate epoxidase, a
      cytochrome P450 monooxygenase. Assays with intact glands incubated in vitro and
      with gland homogenates have identified a series of 1,5-disubstituted imidazoles
      as potent inhibitors of the enzyme. We have designed, synthesized and tested two
      imidazoles, diazirine-Ice T and benzophenone-Ice T, in which a radiolabeled and
      photoactivatable diazirine or benzophenone group was introduced to label the
      hydrophobic substrate binding site of the enzyme. Our results show that these
      bifunctional compounds inhibit JH III synthesis by intact glands as well as
      methyl farnesoate epoxidation by gland homogenates. Moreover both compounds
      selectively label a protein of ca. 55 kDa in corpora allata of the cockroach,
      Diploptera punctata. These photoaffinity labels, which use an imidazole to
      coordinate to the heme iron and a photoreactive group to modify the hydrophobic
      substrate binding pocket, are specific and effective probes for the molecular
      analysis of methyl farnesoate epoxidase.

PMID- 7627205
TI  - Biosynthesis of salivary prostaglandins in the lone star tick, Amblyomma
      americanum.
AB  - Dopamine-induced saliva from ticks fed [3H]arachidonic acid contained the
      radiolabelled prostaglandins E2, F2 alpha, D2, and B2, the latter probably
      derived from PGE2 owing to the alkalinity of tick saliva. Prostaglandin
      synthetase (PGS) activity in the salivary gland homogenate from the lone star
      tick, Amblyomma americanum, could not be detected by standard radiometric
      methodologies successfully employed for tissues from many animal species,
      including numerous arthropods. Modifications to the assay conditions had no
      effect. The presence of a PGS-inhibitor in the salivary glands was ruled out. It
      is postulated that the PGS in A. americanum salivary glands may be considerably
      different from that found in other animals, including vertebrate hosts.

PMID- 7627206
TI  - Eicosanoid biosynthesis by hemocytes from the tobacco hornworm, Manduca sexta.
AB  - We describe eicosanoid biosynthesis by microsomal-enriched preparations of
      hemocytes from larvae of the tobacco hornworm Manduca sexta. Four major
      prostaglandins, PGA2, PGE2, PGD2, and PGF2 alpha, and a lipoxygenase product that
      co-chromatographed with 15-hydroxyeicosatetraenoic acid (HETE) were synthesized
      under most conditions. The HETE's fraction was the predominant product.
      Eicosanoid biosynthesis was sensitive to experimental conditions, including
      incubation time, temperature, and protein concentration. Optimal biosynthesis was
      observed with 1.5 mg of microsomal-enriched protein, incubated at 30 degrees C
      for 2 min. The hemocyte preparation is sensitive to low dosages of naproxin and
      esculetin. As in mammals, most lipoxygenase activity (87%) was localized in the
      cytosolic fraction of hemocytes. Unlike mammals, in which PGH synthase is
      associated with intracellular membranes, the hemocytic activity was detected in
      microsomal (59%), cytosolic (35%) and mitochondrial fractions (5%).

PMID- 7627207
TI  - Regulation of enzymatic activity involved in sex pheromone production in the
      housefly, Musca domestica.
AB  - Ovarian produced ecdysteroids regulate sex pheromone production in the female
      housefly, inducing the synthesis of (Z)-9-tricosene (Z9-23:Hy), cis-9,10
      epoxytricosane, (Z)-14-tricosen-10-one and methylalkanes. Experiments were
      performed to gain a detailed understanding of the processes affected by 20
      hydroxyecdysone (20-HE) that result in sex pheromone production as the female
      becomes reproductively mature. A novel microsomal fatty acid synthetase (FAS) is
      present in the epidermal tissue and plays a role in producing the methyl-branched
      fatty acid precursors to the methylalkanes. This FAS is released from the
      microsomes in the presence of 3 M KCl. A major enzyme activity influenced by 20
      HE is the fatty acyl-CoA elongation system. A shift in the chain length
      specificity of the products of the elongation system causes the change in the
      chain lengths of the alkenes produced to switch from C27 and longer in the
      previtellogenic female to C23 in the mature female. Data is presented indicating
      that it is the condensation activity of the elongation system that is affected.
      Z9-23:Hy arises from a 24 carbon acyl group which is reduced to an aldehyde, and
      then converted to the hydrocarbon. Data is presented demonstrating that it is the
      fatty acyl-CoA derivative and not the free fatty acid that is the substrate.
      There does not appear to be a chain length specificity which regulates the
      conversion of fatty acyl-CoAs to hydrocarbons as both 24 and 28 carbon fatty acyl
      CoAs are converted to hydrocarbon by both males and females of all ages.

PMID- 7627208
TI  - The effect of popcorn and carbonization on neodymium: YAG laser dosimetry in the
      canine model.
AB  - Neodymium:YAG laser irradiation of the canine prostate provides an experimental
      model for the study of the laser-tissue interaction in laser prostatectomy.
      Prostate irradiation was undertaken using right-angle-firing laser fibers through
      an open suprapubic cystotomy, and the procedure was monitored by video endoscopy
      via a perineal urethrostomy. The effects of popcorn and surface carbonization on
      intraprostatic heating profiles were determined by interstitial thermometry. We
      found that popcorn reduced intraprostatic temperatures but that continued
      irradiation resulted in the restoration of heating. Carbonization resulted in the
      loss of heating ability deep in the prostate. These observations allow the
      urologist to understand the thermal implications of observed surface change and
      to modify lasing parameters during surgery to obtain the desired laser-tissue
      interaction.

PMID- 7627209
TI  - Depth of penetration of the neodymium: yttrium-aluminum-garnet laser in the human
      prostate and clinical results of high-dose laser energy in 50 patients.
AB  - We evaluated the treatment of the human prostate with the Nd:YAG laser using a
      Cytocare Prolase II fiber. We utilized this first in 12 patients prior to radical
      prostatectomy and then appropriately serially sectioned the prostate to measure
      the depth of penetration. The studies clearly revealed that 60 W of power and 60
      s of pulse duration gave the most consistent depth of penetration in the human
      prostate model. This depth of penetration averaged 2 cm in the glands that were
      removed. At the same time there was absolutely no evidence of damage to the
      neurovascular bundle or to the capsule of the prostate using the above-mentioned
      dosimetry regime. This study was then transferred to our initial experience in
      treating 50 patients with benign prostatic hypertrophy and obstructive voiding
      symptoms. The first 25 patients were also treated with so-called spot radiation
      of the prostate, whereas the second 25 patients were treated by total
      photoirradiation of all visible endoscopic tissue. The results reveal that both
      groups of patients had a fairly highly satisfactory result as measured
      objectively with American Urological Association (AUA) symptom scores and uroflow
      studies. In the latter group (photoirradiation of all visible endoscopic tissue)
      a significantly higher dose of laser energy was utilized and a smaller failure
      rate was noted on a long-term basis in patients who subsequently came to
      transurethral resection of the prostate (TURP) because of failure of the laser
      procedure.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7627210
TI  - Post-stroke rehabilitation: assessment, referral, and patient management. U.S.
      Department of Health and Human Services Public Health Service. Agency for Health
      Care Policy and Research.
AB  - This Quick Reference Guide for Clinicians contains highlights from Post-Stroke
      Rehabilitation, Clinical Practice Guideline No. 16, which was developed by a
      multidisciplinary, private-sector panel comprised of health care professionals
      and a consumer representative. The Quick Reference Guide for Clinicians is an
      example of how a clinician might implement the panel's findings and
      recommendations on the overall management of stroke patients who need post-stroke
      rehabilitation programs or services before returning to a family or other living
      environment. Topics include medical management of patients, systematic assessment
      and evaluation of patients throughout acute care and rehabilitation, referring
      patients to appropriate rehabilitation programs, managing the rehabilitation
      process, discharging patients from rehabilitation programs, and reintegrating
      patients into family and community environments.

PMID- 7627211
TI  - Rewriting French health care.

PMID- 7627212
TI  - Nurturing new physician execs.

PMID- 7627213
TI  - More med students choosing primary care.

PMID- 7627214
TI  - Women in Denver ERs often victims of domestic violence.

PMID- 7627215
TI  - Litigation ... indirect medical education funding.

PMID- 7627216
TI  - Pharmaceuticals ... Producer Price Index for wholesale pharmaceuticals has been
      overstating drug price increases since 1984.

PMID- 7627217
TI  - Severance side effects.

PMID- 7627218
TI  - Power tilt.

PMID- 7627219
TI  - Clinical research ... older family members at high risk for certain cancers.

PMID- 7627220
TI  - Consumers ... patient satisfaction may depend as much on the type of specialty
      that doctors practice.

PMID- 7627221
TI  - Liability ... breast cancer--and delays in diagnosing it.

PMID- 7627222
TI  - Why executive teams fail and what to do.
AB  - Strife-torn management teams in hospitals and other health care organizations are
      hindering progress toward real change in the field. What can be done? CEOs and
      other senior executives often shy away from the "human" issues, but successfully
      dealing with those concerns will help management teams conquer the business
      issues.

PMID- 7627223
TI  - The new equation.
AB  - What the formula doesn't say is what happens to the other half of all workers,
      the half no longer needed. Nor does it make clear that as well as being paid
      twice as much, the favored half will also have to work twice as hard. Hence the
      paradox that half of the people have money but no time, and the other half have
      time but no money.

PMID- 7627224
TI  - Who will represent health systems in the year 2000?

PMID- 7627225
TI  - How one hospital association became the Healthcare Forum. Interview by Terese
      Hudson.
AB  - In 1987, the Association of Western Hospitals, a San Francisco-based educational
      organization became the Healthcare Forum, directed at improving the leadership
      skills of senior management teams. More recently, the organization has put an
      emphasis on training leaders in methods to make their communities healthier.
      While the Forum has fewer members than it did as a 13-state association, they are
      more far-flung: members reside in all 50 states and 38 counties. Forum CEO
      Kathryn Johnson told senior writer Terese Hudson about how and why the group
      reinvented itself.

PMID- 7627227
TI  - Market Profile. Los Angeles.

PMID- 7627226
TI  - Trustee tension.

PMID- 7627228
TI  - Profiles in service (1986-1995). The 1995 Foster G. McGaw Prize winner: Our Lady
      of Lourdes Medical Center, Camden, New Jersey.

PMID- 7627229
TI  - Predatory pricing hits health care.

PMID- 7627230
TI  - The cutting edge.
AB  - With managed care payment becoming the norm, employers actively pursuing keener
      benefits management, health care markets evolving at warp speed, and clinical and
      information technologies spawning new capabilities every day, the cutting edge in
      health care keeps slicing ever-deeper. With that in mind, we at Hospitals &
      Health Networks have developed a browser's compendium of some of the leading
      people, places (organizations and programs) and technologies that are helping
      move the field forward into the next stage. Each entry is unique; what they all
      share is an innovative quality that others will emulate.

PMID- 7627231
TI  - Mechanical bowel preparation in review.
AB  - Mechanical bowel preparation is necessary for colorectal surgery, colonoscopy,
      and diagnostic radiological studies. While the techniques of bowel cleansing
      employed for each of these procedures are similar, indication-specific methods of
      preparation vary. Peroral lavage, traditional cathartics and enemas, and per
      rectal lavage are discussed in this overview.

PMID- 7627232
TI  - Business process quality management: a step beyond continuous quality
      improvement.
AB  - Customer demands and financial pressures have forced hospitals to reassess the
      quality of their services and the efficiency with which they are delivered. A
      number of institutions have turned to continuous quality improvement methods to
      help streamline specific processes. For institutions to survive, however, they
      must look beyond specific processes to broader issues of scope of practice. One
      hospital's use of Juran's BPQM framework helped position the institution for
      future economic demands.

PMID- 7627233
TI  - Preventing cardiopulmonary arrest via enhanced vital signs monitoring.
AB  - A physician-nurse collaborative team developed and implemented a research-based
      protocol and algorithm for improving vital signs monitoring and early
      intervention for at-risk patients. Project evaluation showed that in general the
      protocol and algorithm were used appropriately and consistently and prevented
      negative patient outcomes.

PMID- 7627234
TI  - Family members' roles in long-term care.
AB  - A qualitative study was conducted using a participation-observation methodology
      to determine the role and function of family members visiting in long-term care.
      Observations, interactions, tasks, and family responses are reported and
      discussed. Recommendations for nurses to assist families are provided.

PMID- 7627235
TI  - Preemptive analgesia: a research review.
AB  - Current clinical research studying the administration of local anesthetics,
      opioids, and nonsteroidal anti-inflammatory agents prior to various types of
      surgery are reviewed. These agents can reduce pain and improve patient management
      in the postoperative period, but this technique can be controversial.
      Implications for nurses are discussed.

PMID- 7627236
TI  - Using critical thinking skills to improve medication administration.
AB  - Nurses need critical thinking skills to provide competent care. For interventions
      such as drug administration, a system of critical thinking assists nurses to
      accomplish tasks safely and efficiently. The use of the "think and apply" model
      provides nurses with a practical way to integrate critical thinking skills into
      practice.

PMID- 7627237
TI  - Hormone replacement therapy and cardiovascular health in midlife women.

PMID- 7627238
TI  - Learning the language of the DSM-IV.

PMID- 7627239
TI  - Strategies to prevent cardiac arrest: research synopsis.

PMID- 7627240
TI  - Therapeutic beds: an overview.

PMID- 7627241
TI  - Managing change--before it manages you!

PMID- 7627242
TI  - Withholding and withdrawing life-sustaining treatment.

PMID- 7627243
TI  - Clarification needed for pressure sore incidence.

PMID- 7627244
TI  - Orlistat (Ro 18-0647), a lipase inhibitor, in the treatment of human obesity: a
      multiple dose study.
AB  - OBJECTIVE: To evaluate efficacy and tolerability of the lipase inhibitor Orlistat
      (Ro 18-0647) in doses of 10, 60 and 120 mg three times a day in addition to a
      mild hypocaloric diet containing 30% of calories as fat. DESIGN: 4 week single
      blind placebo run-in period of diet alone followed by a 12 week double-blind,
      placebo-controlled, randomized treatment period. SETTINGS: Five European
      outpatient clinics specializing in endocrinology and/or the treatment of obesity,
      one central laboratory. SUBJECTS: Of 237 healthy obese subjects meeting the
      inclusion criteria, 188 showed compliance to the diet during the run-in period
      and were randomized for the treatment period. MAIN OUTCOME MEASURES: Primary
      efficacy criterion was the difference in weight loss after 12 weeks of treatment
      between the Orlistat treated groups and the diet alone group. Secondary efficacy
      criteria were changes in serum total, HDL- and LDL-cholesterol. RESULTS: Compared
      to placebo a mean (+/- s.e.) additional weight loss of 0.63 +/- 0.54 kg with 30
      mg a day (P = 0.246), 0.71 +/- 0.55 kg with 180 mg a day (P = 0.190) and 1.75 +/-
      0.54 kg with 360 mg a day was seen (P = 0.001) or Orlistat was observed. Overall
      data indicated dose-dependency. Small decreases were seen in total and LDL
      cholesterol (significant in the 180 and 360 mg a day groups) and LDL- to HDL
      cholesterol ratio (significant in the 360 mg a day group only). Mild, mostly
      gastrointestinal side effects were observed more frequently in the Orlistat
      groups and caused premature withdrawal from the study in only four patients. No
      marked laboratory abnormalities were shown, including the lipid-soluble vitamins
      A, D and E. CONCLUSION: Orlistat, in an apparently dose-dependent manner, leads
      to additional weight loss compared to diet alone and overall, is well tolerated.

PMID- 7627245
TI  - Relationship between energy expenditure and visceral fat accumulation in obese
      women submitted to adjustable silicone gastric banding (ASGB).
AB  - OBJECTIVE: To analyze the relationship between visceral fat accumulation and
      resting energy expenditure in obese women and to evaluate the effects of a severe
      weight loss both on energy expenditure and on fat distribution. DESIGN: Twelve
      premenopausal women, aged 19-50 years, undergoing adjustable silicone gastric
      banding (ASGB) for morbid obesity participated at the study. The patients were
      evaluated twice. The baseline evaluation was performed immediately before
      surgery. After surgery, a diet specifically developed for patients submitted to
      gastric restriction (2.5 MJ/day) was given to the patients. The second evaluation
      was performed 6 months after surgery. MEASUREMENTS: Resting metabolic rate (RMR)
      was determined by indirect calorimetry. Total fat area (TFA), visceral fat area
      (VFA) and subcutaneous fat area (SFA) were measured by abdominal computed
      tomography. Fat mass (FM) and fat free mass (FFM) were derived by bioelectrical
      impedance analysis. RESULTS: At baseline, RMR was positively related to VFA (r =
      0.60, P < 0.05). ASGB induced a highly significant weight loss of 24.4 +/- 9.0
      kg. This weight reduction was mainly due to a loss of FM (68.5 +/- 10.8 vs 48.5
      +/- 9.2 kg, P < 0.001), whereas FFM was only slightly reduced (52.6 +/- 4.0 vs
      47.9 +/- 4.6 kg, P < 0.05). The BMI reduction was positively related to the
      baseline BMI and FM values (r = 0.61, P < 0.05 and r = 0.55, P < 0.05,
      respectively). There was no significant correlation between the BMI reduction and
      the baseline variables of fat distribution, nor between the BMI reduction and the
      basal RMR. Weight loss was accompanied by modifications of fat distribution. In
      particular, the reduction of VFA after surgery was strictly related to the VFA
      values at baseline (r = 0.91, P < 0.001). Weight loss induced a significant
      reduction of RMR (7.96 +/- 1.77 vs 6.57 +/- 6.90 MJ/day; P < 0.01). The reduction
      of the RMR observed with weight loss was significantly related to the FFM loss (r
      = 0.63, P < 0.05), whereas no correlations were found between the changes of RMR
      and the FM loss. Regarding to fat distribution, the reduction of the RMR was
      significantly related to the visceral fat loss (r = 0.57, P < 0.05), but not to
      the modifications of total or subcutaneous fat area. The independent contribution
      of the modifications of FFM, FM, and visceral fat to the changes of RMR was
      analyzed by multiple regression analysis. In this model, both FFM and visceral
      fat changes resulted independently related to the RMR. CONCLUSIONS: (1) visceral
      fat accumulation was a significant predictor of RMR in the very obese woman; (2)
      visceral obese women lost more visceral fat than subcutaneous ones; (3) the
      reduction of the RMR observed during weight loss could partly be explained by a
      reduction of visceral fat mass.

PMID- 7627246
TI  - Caffeine pharmacokinetics in obesity and following significant weight reduction.
AB  - OBJECTIVES: To compare caffeine pharmacokinetics (200 mg single oral dose)
      between obese and lean subjects and in obese subjects prior to and following
      weight reduction. In the obese group antipyrine (1000 mg single oral dose)
      pharmacokinetics were also evaluated one week before caffeine administration.
      SETTING: Teaching university hospital. DESIGN: Single dose, open study. SUBJECTS:
      Twenty obese subjects (Group A) (BMI exceeding 30 kg/m2), referred from the
      outpatient metabolic clinic and 14 lean (Group B) subjects participated in the
      study. Weight (mean +/- s.d.) and BMI were significantly greater in the obese
      than the lean subjects (110.4 +/- 19.2 vs 66.9 +/- 13.3 kg respectively, and 38.5
      +/- 5.8 vs 22.6 +/- 1.7 kg/m2 respectively, P < 0.001). INTERVENTIONS: Single
      dose oral administration of caffeine (200 mg) and antipyrine (1000 mg) in Group A
      and only caffeine in Group B. Twice single dose oral administrations of caffeine
      (200 mg) in six subjects (Group C), prior to and following weight loss. MAIN
      OUTCOME MEASURES: Caffeine and antipyrine pharmacokinetics were derived from the
      plasma concentrations-time curves. RESULTS: Caffeine elimination half-life (T1/2)
      and clearance (CLo) were similar in obese and lean subjects (6.54 +/- 2.85 vs
      6.08 +/- 2.23 h respectively and 100.7 +/- 49.5 vs 82.6 +/- 34.0 ml/min
      respectively, P > 0.05). Caffeine Varea was greater in group A than in Group B
      (48.3 +/- 11.4 vs 40.1 +/- 13.0 L respectively, P = 0.06) but when corrected for
      body weight significantly reduced values were obtained in the obese group (0.44
      +/- 0.06 vs 0.59 +/- 0.10 L/kg respectively, P < 0.001). In group A subjects
      caffeine and antipyrine Varea were similar (48.3 +/- 11.4 vs 49.9 +/- 9.3 L
      respectively, P > 0.3). Caffeine T1/2 and CLo were not significantly altered by
      the 30.2 +/- 12.3 kg weight loss obtained in Group C subjects, but caffeine Varea
      was significantly reduced (55.6 +/- 9.3 L before, 47.8 +/- 9.5 L after, P < 0.04)
      and Varea corrected for body weight was significantly increased (0.46 +/- 0.03
      L/kg before, 0.52 +/- 0.05 L/kg after, P < 0.05). CONCLUSIONS: Caffeine
      pharmacokinetics are only minimally altered by obesity. The use of caffeine
      containing drugs in obese subjects does not necessitate significant dosage
      modification.

PMID- 7627247
TI  - Is there a relationship between obesity and intracranial hypertension?
AB  - BACKGROUND: Intracranial hypertension and obesity have been reported in recent
      studies of patients with periorbital venous vasculitis. These findings indicate
      that obese patients should be investigated for signs of inflammation in serum and
      lumbar cerebrospinal fluid (CSF) pressure. PATIENTS AND METHODS: Twenty obese
      females, aged 27-68 years participated in the study of associated symptoms, signs
      of inflammation in serum, intracranial hypertension and magnetic resonance
      imaging of the brain (MR). Twenty randomly selected age- and sex-matched females
      were also investigated for associated symptoms and MR as controls. RESULTS: There
      were no statistically significant differences in associated symptoms and diseases
      except for infertility (P < 0.05) between the two groups. The values for
      orosomucoid, haptoglobin, IgG, IgM and tests for rheumatic and antinuclear
      factors were significantly increased in the obese group compared with normal
      values at the hospital. The lumbar CSF pressure was increased above 20 cm water
      in 79% and above 25 cm water in 42% in the obese patients. MR showed that the
      subarachnoidal space in the obese patients were significantly smaller than in the
      controls. CONCLUSIONS: Signs of inflammation in serum, intracranial hypertension
      and decreased subarachnoidal space were statistically significantly more common
      in patients with obesity, than in controls.

PMID- 7627248
TI  - Differences in substrate metabolism between self-perceived 'large-eating' and
      'small-eating' women.
AB  - OBJECTIVE: To compare different aspects of intermediary metabolism in self
      perceived 'small-eating' females and self-perceived near normal weight 'large
      eating' females and relate the data to those reported for Pima Indians who have
      the world's highest prevalence of non-insulin dependent diabetes mellitus and
      obesity. DESIGN: Make repeat measurements of rates of oxygen consumption, carbon
      dioxide production and blood metabolites in 'large-' and 'small-eating' females
      at rest, during different activities and after ingestion of a standardised liquid
      meal. SUBJECTS: Nine self perceived, 'large-eating' females and nine self
      perceived 'small-eating' females. MEASUREMENTS: Resting metabolic rates (RMR),
      respiratory quotient (RQ) values and plasma insulin, glucagon insulin-like growth
      factor (IGF-1), dehydroepiandrosterone sulphate (DHEA-SO4) and glucose. RESULTS:
      RMR (adjusted for FFM) averaged 3891 +/- 93 J/min in the 'small-eaters' and 3375
      +/- 107 J/min in the 'large-eaters' for ten consecutive measurements conducted at
      30 min intervals during the control period for the measurement of the thermic
      effect of food. Over this period the average RQ for the 'small-eating' women
      (0.81) was significantly greater than that of the 'large-eating' women (0.78).
      The two groups responded similarly to an oral glucose tolerance test but the
      concentration of DHEA-SO4 in plasma was 35% higher in the 'small-eaters'.
      CONCLUSION: The 'small-eating' women may have a greater risk of weight gain but
      they counteract this tendency by maintaining high activity levels.

PMID- 7627249
TI  - Relationships between biochemical abnormalities and anthropometric indices of
      overweight, adiposity and body fat distribution in Japanese elementary school
      children.
AB  - OBJECTIVE: To determine the anthropometric indices linked to the biochemical risk
      factors for atherosclerosis in Japanese obese elementary school children, ages
      ranging from 6 to 12 years. DESIGN: Cross-sectional study of obese children based
      on fasting blood samples. SETTING: Outpatient clinic of University Hospital.
      SUBJECTS: 65 consecutive patients with simple obesity (38 boys and 27 girls), and
      age-matched controls, 184 boys and 205 girls. MAIN OUTCOME MEASURES: Percent
      obesity and body mass index as indices of being overweight; percent body fat and
      the sum of four skinfold thicknesses as indices of adiposity; waist-to-hip
      circumference ratio and waist-to-thigh circumference ratio as indices of body fat
      distribution. The anthropometric indices were standardized by calculating
      standard deviation scores based on data from control children. RESULTS: In the
      obese boys, all six anthropometric indices studied correlated closely with serum
      biochemical indices, and strong correlations were observed among the indices of
      overweight, adiposity and body fat distribution. In contrast, only the indices of
      body fat distribution, not those of overweight or of adiposity, were correlated
      with serum biochemical indices in the obese girls. No relationship was found
      between the indices of body fat distribution and the other anthropometric indices
      in the obese girls. Thus, the profile of the obese girls differed from that of
      their male counterparts. CONCLUSION: The results suggest that body fat
      distribution is related to certain biochemical complications of childhood
      obesity, and that androgyny in fat patterns induces metabolic derangements in
      children.

PMID- 7627250
TI  - Compliance to dietary advice directed towards increasing the carbohydrate to fat
      ratio of the everyday diet.
AB  - OBJECTIVE: To assess the effects, on food intake, body weight and body
      composition, of compliance to advice aiming at increasing the carbohydrate to fat
      ratio of the everyday diet without imposing voluntary restriction on the amount
      of food consumed. DESIGN: Eight moderately overweight women (body mass index > 27
      kg/m2, relative body fat mass > 30%) received dietary advice during a 2 month
      period. Additionally, each evening the subjects had to consume a meal
      artificially enriched with 13C-glucose in order to assess their compliance from
      the 13CO2 enrichment in expired air. MEASUREMENTS: Dietary intakes, body weight,
      body composition and individual compliance. RESULTS: The energy derived from fat
      decreased from 44 +/- 1% to 31 +/- 1% and the proportion of carbohydrate
      increased from 38 +/- 2% to 50 +/- 1%, whereas the absolute carbohydrate intake
      remained constant (182 +/- 18 g/d). Energy intake decreased by 1569 +/- 520 kJ/d.
      There was a net loss of fat mass (1.7 +/- 0.7 kg, P = 0.016) with fat free mass
      maintenance. Dietary compliance ranged from 20 to 93% (mean: 60 +/- 8%) and was
      positively correlated to the loss of body fat mass. CONCLUSION: Advice aiming at
      increasing diet's carbohydrate to fat ratio induces a loss of fat mass with fat
      free mass maintenance.

PMID- 7627251
TI  - Lipoprotein lipase gene polymorphisms: associations with hypertriglyceridemia and
      body mass index in obese people.
AB  - OBJECTIVE: To compare body mass index (BMI), lipid, lipoprotein and
      apolipoprotein concentrations according to the Hind III and Pvu II restriction
      polymorphisms of the LPL gene in obese subjects. DESIGN: Cross sectional study of
      anthropometric and lipid variables in relation to genetic factors. SETTING:
      Nutrition Outpatient Clinic of Bichat Hospital in Paris, France. SUBJECTS: 236
      unrelated patients (162 women and 74 men) were selected on the basis of 120% of
      ideal body weight. MAIN OUTCOME MEASURES: Anthropometry (body mass index, waist
      to hip ratio), blood lipids and lipoproteins, determination of LPL Hind III and
      Pvu II genotypes. RESULTS: Digestion with Hind III generated two alleles, H1
      (absence of cutting site) and H2 (presence of cutting site), with frequencies of
      0.30 and 0.70 respectively. Digestion with Pvu II generated two alleles P1 and P2
      with frequencies of 0.49 and 0.51 respectively. The Hind III polymorphism was
      significantly associated with body mass index (BMI) (P < 0.05). The H2H2 genotype
      was associated with hypertriglyceridemia: 68% of the hypertriglyceridemic
      subjects have the H2H2 genotype vs 43% of the normotriglyceridemic group (P <
      0.05). Plasma triglyceride levels varied significantly among the Hind III
      genotypes, H2H2 genotype having the highest total and VLDL-triglyceride levels;
      the Hind III polymorphism also showed a significant association with HDL2
      cholesterol. These associations were only seen in women and were not explained by
      the variations in BMI and age. No significant associations were found between
      lipid traits and Pvu II genotype. CONCLUSION: These results suggest that genetic
      variation in the LPL gene in obese subjects is associated with
      hypertriglyceridemia and possibly with a predisposition to obesity.

PMID- 7627252
TI  - Prognostic markers for diet-induced weight loss in obese women.
AB  - OBJECTIVE: To identify prognostic metabolic and hormonal markers for long-term
      weight loss outcome in obese women. DESIGN: Dietary intervention consisting of 36
      weeks treatment by a 4.2 MJ/d low-fat high carbohydrate diet, and follow-up 2 1/2
      years after termination of treatment. SETTING: Outpatient clinic in Copenhagen.
      SUBJECTS: Forty consecutive female obese patients aged 15 to 62 years. MAIN
      OUTCOME MEASURE: Weight loss. RESULTS: The maximum weight loss (mean 16.2 kg, 95%
      CI 14.2-18.2) was positively associated to pre-treatment 24-h energy expenditure
      (P < 0.01), fat oxidation (%) (P < 0.02), plasma dihydrotestosterone (DHT) (P <
      0.01), and to postprandial noradrenaline concentration (P < 0.04). Together these
      factors could explain 41% of the variation in maximum weight loss. Only 24-h EE
      and DHT had predictive power on weight loss after 36 weeks. Weight losses in
      upper and lower tertiles of DHT concentrations were 17.7 kg (14.1-21.4) and 9.8
      kg (6.2-13.3) (P < 0.02). The adjusted relative risk of losing < 10 kg in the
      upper compared to the lower DHT tertile was 12% (4-32%). At 2 1/2 y follow-up 21
      patients had maintained some of the weight loss (54%), while 14 patients had
      maintained > 5 kg weight loss (36%). High levels of pre-treatment DHT were also
      associated with better weight loss at 2 1/2 y follow-up. CONCLUSION: The study
      suggests that in particular DHT, but also 24-h EE, fat oxidation, and plasma
      noradrenaline, may be prognostic markers for weight loss outcome in obese women.

PMID- 7627253
TI  - Intra-abdominal adipose tissue in young children.
AB  - OBJECTIVE: Intra-abdominal adipose tissue (IAAT) is associated with the metabolic
      complications of obesity. However the time course for the development of IAAT is
      not clearly defined because it is generally difficult to measure directly. The
      purposes of this short communication are to present data supporting the existence
      of IAAT in young children using direct measurement with computed tomography
      imaging, and to examine the relationship between IAAT and anthropometric indices
      in 16 healthy children (6.4 +/- 1.2 years; 24.8 +/- 5.4 kg). DESIGN: Total body
      fat (6.4 +/- 3.5 kg) and fat free mass (18.4 +/- 3.6 kg) were determined by
      bioelectrical resistance. Fat distribution was estimated from eight individual
      skinfold measurements, the ratio of three trunk skinfolds to three extremity
      skinfolds (0.78 +/- 0.20), and the waist:hip ratio (0.90 +/- 0.08). RESULTS: Mean
      abdominal subcutaneous adipose tissue (SCAT) was 65.3 +/- 44.8 cm2, and mean IAAT
      was 8.3 +/- 5.8 cm2. The ratio of IAAT to SCAT was 0.15 +/- 0.08, and the ratio
      of IAAT to total body fat was 1.44 +/- 0.84 cm2/kg. IAAT was significantly
      correlated with body weight (r = 0.54; P = 0.03), all skinfold measures (range r
      = 0.60-0.78; P = 0.02 to 0.0003) except at the calf, fat mass (r = 0.69; P =
      0.003), and the trunk to extremity skinfold ratio (r = 0.78; P = 0.0003). There
      was no significant correlation between IAAT and the waist:hip ratio (r = 0.21).
      CONCLUSIONS: These preliminary results establish the existence of IAAT in young
      children and suggest that individual trunk skinfold measurements and the
      trunk:extremity skinfold ratio provide a better indication of IAAT compared to
      the waist:hip ratio. However, as with adults, the relationship between intra
      abdominal adipose tissue and anthropometry in children is complex.

PMID- 7627254
TI  - Methodological studies on single meal food intake characteristics in normal
      weight and obese men and women.
AB  - METHOD: The eating behaviour of 19 normal weight males, 19 obese males, 19 normal
      weight females and 19 obese females was measured by means of VIKTOR, our version
      of the universal eating monitor. The total food intake, the duration of
      consumption, the rate of consumption, the relative rate of consumption and the
      subjective motivation to eat were measured during five homogenous lunch meals to
      analyse how these variables were related to body weight or to sex. Furthermore,
      the stability of the eating characteristics over the five eating occasions were
      tested with pre-defined criteria of stability. The predictive validity of the
      variables measuring subjective motivation to eat and forthcoming food intake was
      also tested. RESULTS: Men ate more food than women; normal weight men by eating
      for a longer time and obese men by eating faster. Females did not slow down the
      eating rate towards the end of the meals as much as males did. The obese subjects
      described themselves as having less motivation to eat prior to meals than normal
      weight subjects. CONCLUSIONS: Total stability, i.e. both relative and absolute
      stability, for all subjects was present for the eating variables intake of food
      and eating rate. Of the variables measuring subjective motivation to eat (desire
      to eat, hunger, fullness and prospective consumption) on visual analogue scales,
      only the variables desire to eat and prospective consumption predicted
      forthcoming food intake.

PMID- 7627255
TI  - Enterostatin from collagen?

PMID- 7627256
TI  - Regulation of gene expression in the central nervous system by stress: molecular
      pathways of stress responses.

PMID- 7627257
TI  - Thyroid hormone action in the cell.

PMID- 7627258
TI  - Highly increased insulin secretion in a patient with postprandial hypoglycemia:
      role of glucagon-like peptide-1 (7-36) amide.
AB  - The mechanism(s) of an inappropriate secretion of insulin is poorly understood.
      We report a case of reactive hypoglycemia associated with an unusually
      exaggerated insulin secretion. The patient, a 32-year-old man, developed frequent
      episodes of postprandial hypoglycemia after interferon treatment was begun for
      chronic type C hepatitis. Oral glucose challenge test confirmed the patient's
      extremely high plasma IRI response, i.e., more than 1000 microU/ml, and that of
      plasma C-peptide 56.9 ng/ml at 90 min, followed by symptomatic hypoglycemia
      (plasma glucose 34 mg/dl) at 240 min. The plasma proinsulin level also was high,
      but the molar ratio of immuno reactive insulin (IRI)/plasma C-peptide and
      IRI/proinsulin was within the normal range. Antibodies to insulin or insulin
      receptor were negative. Plasma IRI response was apparently greater when the
      glucose was given orally than when given intravenously. The response of plasma
      glucagon-like-peptide (GLP)-1 to oral glucose was quite high (from baseline of
      45.5 to 303.2 pmol/L) and showed a close parallel with the change in the plasma
      IRI concentration. The greatly enhanced insulin secretion leading to reactive
      hypoglycemia in this patient may therefore be attributed to the increased
      secretion of GLP-1.

PMID- 7627259
TI  - In vivo effect of cabergoline, a dopamine agonist, on estrogen-induced rat
      pituitary tumors.
AB  - Cabergoline (CG) is a dopamine agonist that inhibits the secretion of prolactin
      (PRL) and growth hormone. In the present study, we evaluated the in vivo effect
      of CG on PRL secretion and the pituitary tumor induced by estrogen. Estrogen was
      administered by subcutaneous injection to 4-week-old Fischer 344 rats weekly for
      10 weeks to induce tumors. On the last day of estrogen administration, doses of
      either CG or bromocriptine (BC), 0.6 mg/kg, were administered as a single oral
      route or chronically, given every third day. Sera and pituitary tumors were
      sampled on each treatment schedule. Serum levels of PRL were measured and the
      pituitary glands were weighed. Immunohistological evaluation was performed by
      optical and electron microscopy. A single dose of CG significantly inhibited the
      serum levels of PRL for 6 days. Following a single dose of BC, the PRL level was
      significantly inhibited only at 6 hours' postadministration. The continued oral
      administration of CG significantly reduced both the serum PRL level and the
      weight of the pituitary during 15 to 60 days of treatment as compared with BC.
      Morphologic studies revealed that CG reduced the size of the cells and of the
      granules, and increased the number of granules per unit area of the cytoplasm.
      These findings suggest that CG inhibits the maturation of PRL secretory granules
      and the secretion of PRL more than its synthesis. Thus, CG induced a prolonged
      lowering of PRL and had a good antitumor effect on rat pituitary tumors induced
      by estrogen.

PMID- 7627260
TI  - Syndrome of inappropriate antidiuresis seen twice in eight years.
AB  - We present a rare case of a 66-year-old woman with the syndrome of inappropriate
      antidiuresis (SIAD) accompanied by an empty sella whose symptoms were seen twice
      in the eight years after the administration of non-steroidal anti-inflammatory
      drugs (NSAID) or prochlorperazine. No diuresis or suppression of the plasma level
      of vasopressin (AVP) was observed after water loading upon cessation of the
      causative agents. Suppression of the renin-aldosterone system and a low plasma
      level of atrial natriuretic peptide (ANP) were observed during natriuresis. The
      plasma levels of AVP were increased after water loadings. Restriction of water
      intake ameliorated the symptoms and reduced hyponatremia. These findings suggest
      that NSAID or prochlorperazine caused overt SIAD twice in eight years. The water
      loading test itself stimulated the release of AVP and a suppression of the renin
      aldosterone system played a more important role in natriuresis than ANP in this
      case.

PMID- 7627262
TI  - Presence of vasoactive intestinal peptide receptor in the hen hypothalamus.
AB  - Radioligand assays of the membrane fraction of hen hypothalamic tissues involving
      the preoptic (HPOA) or median eminence (HMEA) areas revealed the presence of a
      specific binding component to chicken vasoactive intestinal peptide (cVIP) having
      properties of a receptor. The equilibrium dissociation constant (Kd) was 0.70 +/-
      0.07 nM (Mean +/- SEM; N = 5) in HPOA and 1.02 +/- 0.15 nM (N = 5) in HMEA as
      estimated by Scatchard analysis of saturation studies, and was 0.91 +/- 0.11 nM
      (N = 3) (HPOA) and 1.25 +/- 0.09 nM (N = 3) (HMEA) as determined by a kinetic
      analysis. The maximum binding capacity (Bmax) obtained by Scatchard analysis was
      167 +/- 19 fmol/mg protein (N = 5) (HPOA) and 133 +/- 17 fmol/mg protein (N = 5)
      (HMEA). The Kd and Bmax values obtained by Scatchard analysis were similar in the
      two areas of the hypothalamus and in both laying and nonlaying hens.
      Administration of cVIP in vivo caused a decrease in specific cVIP binding. These
      results suggest the presence of a VIP receptor in the hen hypothalamus.

PMID- 7627261
TI  - Siblings with ACTH insensitivity due to lack of ACTH binding to the receptor.
AB  - We report two siblings, a 9-year-old boy and 4-year-old girl, with ACTH
      insensitivity. They were referred to our hospital because of pigmentation of the
      skin. They had normal plasma cortisol and urinary 17-OHCS levels despite markedly
      high plasma ACTH, and these did not respond to consecutive 3-day ACTH-Z
      administration, but plasma aldosterone responded normally to increased plasma
      renin activity after a low sodium diet. We examined the characteristics of ACTH
      receptors in peripheral blood mononuclear leukocytes (MNLs) obtained from the
      patients and their family. Adenylate cyclase generation caused by an addition of
      ACTH did not occur in MNLs from the patients. In studies on ACTH binding to MNLs,
      a lack of high-affinity ACTH binding was observed in the patients. These results
      suggest that the patients have a defect in ACTH binding to the receptors,
      resulting in ACTH insensitivity. The reason for this defect in ACTH binding
      remains unclear because no significant mutation in the ACTH receptor DNA sequence
      was detected in the MNLs of these patients.

PMID- 7627263
TI  - Long-term effects of dietary fiber supplementation on serum glucose and
      lipoprotein levels in diabetic rats fed a high cholesterol diet.
AB  - We have shown that cholesterol-fed diabetic rats developed atheromatous lesions
      in the aorta and coronary arteries, which were not observed in cholesterol-fed
      diabetic rats receiving concomitant supplementation with 15% glucomannan, a
      soluble dietary fiber concentrate. The present study was designed to examine the
      effects of the dietary fiber supplementation on serum levels of glucose and
      lipoproteins in cholesterol-fed diabetic rats. Feeding a diet containing 1.5%
      cholesterol (wt/wt) and 0.37% cholic acid for 18 weeks to rats made diabetic by
      streptozotocin (35 mg/kg body weight, iv) produced moderate hyperglycemia and
      moderate hypercholesterolemia, the latter being characterized by high
      concentrations not only of low density lipoproteins but also intermediate density
      lipoproteins and very low density lipoproteins. These changes in serum
      lipoproteins and hyperglycemia were substantially reduced by 18 weeks of
      supplementation with glucomannan but high density lipoprotein cholesterol and
      triglyceride levels did not change after feeding a cholesterol-rich diet in the
      presence or absence of glucomannan supplementation. These results suggest that
      amelioration in hyperlipoproteinemia and hyperglycemia induced by the dietary
      fiber supplementation may help retard or prevent the atheromatous formation found
      in cholesterol-fed diabetic rats.

PMID- 7627264
TI  - Apoptosis in thyroid diseases: a histochemical study.
AB  - Recent studies demonstrate that apoptosis is an important process in
      physiological and pathological cell death. We examined the apoptotic phenomena in
      thyroid tissues by two methods: immunohistological and in situ end-labeling of
      fragmented DNA (ISEL). In thyroid tissues from patients with Hashimoto's
      thyroiditis and thyroid cancer, fragmented nuclear DNA and LeY (apoptosis
      associated antigen) were observed. In tissues from patients with Graves' disease,
      LeY and bcl-2 oncoprotein were expressed, but no ISEL positive cells were
      observed. In contrast, thyrocytes in normal thyroid tissues were not stained with
      ISEL or anti-LeY antibodies (Abs). Fas antigen (Ag) was expressed in various
      thyroid tissues, including normal subjects. The clinical meaning of this was not
      determined. These results suggest that the apoptotic process takes place in
      Hashimoto's thyroiditis and thyroid cancer, and is overcome in Graves' disease by
      bcl-2 expression.

PMID- 7627265
TI  - Immunoreactive (ir)-transforming growth factor (TGF)-beta in rat corpus luteum:
      ir-TGF beta is expressed by luteal macrophages.
AB  - Western analyses and immunohistochemistry of transforming growth factor beta 1
      (TGF beta 1) and TGF beta 2 were performed in rat luteal tissue at either the
      functional or regressing stage. Anti-TGF beta 1 or TGF beta 2 was localized
      simultaneously to macrophages within cultured luteal cells and frozen ovarian
      sections. By Western analysis, an active form of TGF beta (25 kDa) was detected
      clearly with anti-TGF beta 2 but only faintly with anti-TGF beta 1, and the
      former band from functional corpora lutea was more intense than that from
      regressing ones. Treatment with prolactin (PRL), a luteotropic hormone in
      rodents, also increased the intensity of 25 kDa TGF beta 2 in the corpus luteum.
      Several specific bands with higher molecular weights than 25 kDa were also
      recognized with anti-TGF beta 1 or TGF beta 2; they are probably ascribed to
      latent TGF beta s and/or TGF beta precursor proteins. In cultured luteal cells
      and frozen ovarian sections, many anti-TGF beta 1 or anti-TGF beta 2 positive
      cells from functional corpora lutea of pseudopregnant rats were double-stained
      with anti-macrophage. There were numerous macrophages in structurally regressing
      corpora lutea of pseudopregnant rats, but most of them were not stained with anti
      TGF beta s. These results suggest that the expression of TGF beta, at least for
      TGF beta 2, is under the influence of PRL in the rat corpora lutea, and that
      macrophages are responsible for some, if not all, of the immunoreactive-TGF beta
      in rat luteal tissue.

PMID- 7627267
TI  - Pathophysiological significance of plasma total renin and prorenin in patients
      with diabetes mellitus.
AB  - To seek the pathophysiologic significance of measuring the concentration of total
      renin instead of prorenin, we determined the plasma total renin concentration by
      immunoradiometric assay and correlated the results with various clinical features
      and laboratory parameters of diabetic complication in 108 patients with diabetes
      mellitus. The plasma prorenin concentration was estimated as the difference
      between the total and active renin concentrations. The plasma total renin and
      prorenin concentrations were high in patients with diabetes mellitus, in contrast
      to the active renin concentration which was slightly decreased. In addition, the
      plasma total renin and prorenin concentrations were higher in patients with
      diabetic complications than in patients without any complication. Multiple
      regression analysis showed that the presence of orthostatic hypotension, diabetic
      retinopathy, and proteinuria is significantly associated with the increased
      plasma total renin and prorenin concentrations. In addition, there was a
      significant positive correlation between the total renin and prorenin
      concentrations. These results suggest that both the plasma total renin
      concentration and the prorenin concentration are closely related to diabetic
      complications. Determination of the plasma total renin concentration by
      immunoradiometric assay as a substitute for prorenin could be a powerful tool in
      elucidating the mechanism for the increased plasma prorenin in diabetes mellitus.

PMID- 7627266
TI  - Exacerbation of rheumatoid arthritis after removal of adrenal adenoma in
      Cushing's syndrome.
AB  - A 46-year-old woman with rheumatoid arthritis had been on non-steroidal
      antiinflammatory agents for eighteen years until she developed cushingoid
      features and hypertension resistant to antihypertensive drugs. She had high
      plasma cortisol and 24 h urinary 17-hydroxycorticosteroids (17HCS) which were not
      suppressed by 8 mg dexamethasone per day for two days. The circadian rhythm of
      plasma cortisol was absent and plasma ACTH concentrations were suppressed before
      and after intravenous administration of CRH. Abdominal computed tomography
      demonstrated a tumor (3.0 x 3.0 x 2.3 cm) in the right adrenal gland and a 131I-6
      beta-19-nor-methylcholesterol scan revealed marked uptake on the same side. The
      patient underwent a right adrenalectomy and the diagnosis of a cortisol secreting
      benign adenoma was histologically confirmed. Blood pressure declined and
      cushingoid features regressed, but three months after the operation and while the
      patient was on replacement, she complained of pain on motion, marked tenderness
      and swelling of fingers, wrists, elbows, knees and foot joints, and had very high
      rheumatoid factors. Treatment with immunosuppressive drugs and oral and
      intraarticular administration of glucocorticoids were necessary to relieve the
      clinical symptoms of rheumatoid arthritis. In summary, we report a patient with
      rheumatoid arthritis and Cushing's syndrome due to an adrenal adenoma, in whom
      rheumatoid arthritis was exacerbated after curing the Cushing's syndrome. This
      suggests that it is imperative to follow the development and/or course of
      autoimmune diseases after the treatment of Cushing's syndrome.

PMID- 7627268
TI  - Characteristics of prolactin secretion in normal and estrogen-treated pituitaries
      of rats at the single cell level: analysis by reverse hemolytic plaque assay.
AB  - We studied PRL release from individual pituitary cells in normal and estrogen
      (E2)-treated female Fischer 344 rats by means of a reverse hemolytic plaque
      assay. In this assay, the area of the hemolytic plaque around a pituitary cell is
      proportional to the amount of hormone secreted from the cell. Multimodal
      distribution of the plaque area was observed in normal pituitary cells, and was
      unchanged in the course of aging. In E2-treated pituitary cells, bimodal
      distribution was found. The heterogeneity of the distribution pattern (functional
      heterogeneity) and PRL secretion from a single pituitary cell decreased in
      association with the length of E2 treatment. The mean plaque area for the E2
      treated pituitary cells was smaller than that for the normal pituitary cells.
      These results suggest that in E2-treated pituitary cells, the functional
      heterogeneity and PRL release from a single cell decrease as tumorigenesis
      progresses.

PMID- 7627269
TI  - A single missense mutation in codon 918 of the RET proto-oncogene in sporadic
      medullary thyroid carcinomas.
AB  - The RET proto-oncogene is expressed in human medullary thyroid carcinoma and
      pheochromocytoma. Recently germline mutations of the RET proto-oncogene were
      reported in four syndromes (MEN 2A, MEN 2B, familial medullary thyroid carcinoma
      and Hirschprung's disease) and somatic mutation was also found in sporadic
      medullary thyroid carcinoma. To determine the incidence of RET mutations in
      medullary thyroid carcinoma in Japan, we investigated 14 medullary thyroid
      carcinomas (comprising 1 case of MEN 2A, 1 case of MEN 2B, 2 cases of familial
      medullary thyroid carcinoma and 10 cases of sporadic). Tumors from all cases were
      screened by PCR-SSCP on exons 10 and 11. DNA sequencing on these exons was
      performed for the hereditary medullary thyroid carcinoma cases. The PCR products
      of exon 16 from tumor DNA were analyzed by means of Fok1 restriction enzyme
      digestion analysis and mutations confirmed by DNA sequencing. We found no
      structural abnormalities in either exon 10 or exon 11 in any of the cases
      examined, but in four of 10 sporadic cases we detected a common point mutation at
      codon 918 (ATG to ACG) in exon 16, where methionine was replaced with threonine.
      Our results support the theory that a point mutation of exon 16 of the RET proto
      oncogene may be related to the oncogenesis of sporadic medullary thyroid
      carcinomas. However, further studies on the entire RET proto-oncogene are needed
      to clarify the relationship between its expression and thyroid tumorigenesis.

PMID- 7627270
TI  - LHRH effects on hippocampal neurons are modulated by estrogen in rats.
AB  - The effect of luteinizing hormone releasing hormone (LHRH) on the neuronal
      activity of CA1 and CA3 regions of the hippocampus was studied by means of
      extracellular recordings in the castrated male, intact male, castrated female,
      and castrated female injected s.c. with 20 micrograms estradiol benzoate (EB) for
      3 days. The basal firing rate of the CA3 neurons of castrated EB-treated female
      rats was significantly lower than that of the neurons in castrated EB-untreated
      female rats as well as male rats, either intact or castrated, whereas that of the
      CA1 neurons was not significantly different from castrated EB-untreated female
      rats. Iontophoretically applied LHRH predominantly resulted in facilitation of
      the neuronal firing in most of the animal groups. In the CA3 region of castrated
      EB-treated female rats, however, inhibition occurred in a large percentage of
      neurons, and the ratio of facilitation, inhibition and no response was
      significantly different from that in castrated EB-untreated female rats. In the
      CA1 region of castrated EB-treated female rats, the predominant effect of LHRH
      was facilitation and the ratio of facilitation, inhibition and no response was
      not significantly different from that in castrated EB-untreated female rats.
      These results suggest that LHRH is involved in increasing the neuronal activity
      of the CA3 region in the hippocampus, and estrogen reduces this LHRH action.

PMID- 7627271
TI  - Tumor-specific mutations in the tyrosine kinase domain of the RET proto-oncogene
      in pheochromocytomas of sporadic type.
AB  - Sporadic pheochromocytomas, sporadic medullary thyroid carcinomas (MTCs),
      pheochromocytomas and/or MTCs in multiple endocrine neoplasia (MEN) 2A or 2B were
      screened for mutations in the tyrosine kinase domain of the RET proto-oncogene by
      direct sequencing of PCR-amplified products or sequencing subcloned DNAs from PCR
      products. All tumors of 4 MEN 2B patients were confirmed to contain a
      heterozygous missense mutation at codon 918 (ATG-->ACG; Met-->Thr) of the RET
      proto-oncogene as well as their leukocytes. The same tumor-specific mutations at
      codon 918 were also found in 5/16 (31%) sporadic pheochromocytomas. These results
      suggest that mutations of the RET proto-oncogene in its tyrosine kinase domain
      play a role not only as the predisposing gene for MEN 2B, but also as a
      tumorigenic factor for pheochromocytomas of sporadic type.

PMID- 7627273
TI  - Histopathological features of atrophic thyroiditis with blocking type-TSH binding
      inhibitor immunoglobulins.
AB  - To investigate the histopathological features of atrophic thyroiditis (AT) with
      blocking type-TSH binding inhibitor immunoglobulins (TBII), the present
      morphological observations were carried out employing additional
      immunohistochemical procedures. Moreover, these were compared with examples of
      goitrous Hashimoto's thyroiditis showing negative TBII (HT). There exist apparent
      differences between AT and HT. In particular, significant follicular atrophy with
      epithelial flattening including decreased positive staining of the follicular
      epithelial cells for thyroglobulin in AT was characteristically observed. These
      results suggest that the mechanism for the development of hypothyroidism in AT
      with blocking type-TBII might be due to suppression of thyroid cell function
      through the inhibition of endogenous TSH stimulation by the blocking antibody
      with subsequent epithelial degenerative destruction.

PMID- 7627272
TI  - Effects of exercise and amenorrhea on bone mineral density in teenage runners.
AB  - In order to elucidate whether exercise and calcium intake can offset bone loss
      due to hypoestrogenemia in teenage girls, the lumbar and femoral bone mineral
      density (BMD) in elite amenorrheic runners (group 1 (n = 8)) was compared with
      those in eumenorrheic athletes (group 2 (n = 15)) and two groups of eumenorrheic
      non-athletic subjects, group 3 (n = 14), and group 4 (n = 15). BMD was measured
      by dual energy x-ray absorptiometry. The subjects in group 1 lived in the
      dormitory, and their calcium intake was controlled to > 1400 mg/day. The subjects
      in groups 1, 2 and 3 were age matched (16-17 years old), but the body weight of
      those in group 2 was significantly greater than that of others. The subjects in
      groups 1, 3 and 4 were weight matched, but group 4 subjects were older by 5 years
      (21.0 +/- 0.2 years old). The lumbar BMD of group 1 was 1.0460 +/- 0.0259, which
      was not statistically different from those in the other groups, while the femoral
      BMD of group 1 was significantly higher than those of groups 3 and 4 at
      trochanter. The lumbar and femoral BMD of group 2 was significantly higher than
      in groups 3 and 4, but was not statistically different from group 1. There were
      no significant differences in serum parathyroid hormone levels, but osteocalcin
      and calcitonin levels of group 1 were significantly lower than those of groups 2
      and 3, and groups 2, 3 and 4, respectively, suggesting that the rate of bone
      formation is suppressed in amenorrheic runners.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7627274
TI  - Young female patient with testosterone-producing adrenocortical adenoma also
      showing signs of subclinical Cushing's syndrome.
AB  - A 28-year old female patient with virilization due to left adrenocortical adenoma
      was studied. The patient had clinical features of hyperandrogenism such as
      hirsutism and a low pitched voice, but not of hypercorticoidism. Plasma
      testosterone and dehydroepiandrosterone-sulfate (DHEA-S) were high. Although the
      basal plasma cortisol concentration and urinary excretion of 17
      hydroxycorticosteroids (17-OHCS) were within the normal range, the absence of
      diurnal variation in plasma cortisol and loss of suppressibility by dexamethasone
      suggested constitutive secretion of cortisol by the tumor. Inappropriate cortisol
      secretion was also supported by blunted ACTH response to provocative stimuli.
      After successful removal of the left adrenal tumor, such endocrinological
      abnormalities were all normalized. Immunohistochemical analysis revealed that
      tumor cells were positively stained for C21 hydroxylase cytochrome P-450 (P
      450C21) and P-450(11) beta which convert 17-hydroxy (OH) progesterone to cortisol
      as well as P-450SCC, 3 beta-hydroxysteroid dehydrogenase and P-450(17) alpha
      which are involved in testosterone biosynthesis. These findings suggest that
      adrenocortical adenoma secretes predominantly testosterone and constitutively
      cortisol in a young woman patient with virilization.

PMID- 7627275
TI  - Desensitization to somatostatin analogue (Octreotide) observed in a patient with
      acromegaly.
AB  - We encountered a 33-year-old female patient with a pituitary growth hormone (GH)
      secreting macroadenoma. The patient was treated with somatostatin analogue
      (Octreotide) in combination with bromocriptine for 2 months before a
      transsphenoidal adenomectomy was carried out. Octreotide (300-800 micrograms/day)
      in combination with bromocriptine was effective in reducing the size of the
      adenoma by 36%, but produced only a marginal decrease in serum GH. After the
      operation, bromocriptine alone (15 mg/day) did not lower the level of GH which
      was produced by residual adenoma tissue. When octreotide (200 micrograms/day) was
      resumed along with the bromocriptine one year after the operation, it effectively
      lowered serum GH for 6 months. Thereafter, octreotide therapy became ineffective
      with a concomitant rise in serum GH and somatomedin C, which was not accompanied
      by an increase in tumor size. This was a rare case of acromegaly that showed
      desensitization to octreotide after long-term treatment.

PMID- 7627276
TI  - Can we use plasma fibronectin levels as a marker for early diabetic nephropathy.
AB  - Although increased plasma fibronectin (PF) levels have been found in diabetic
      patients with microalbuminuria, there is still controversy about its clinical
      implication for detecting early diabetic nephropathy. To evaluate the PF
      concentration as a possible marker for early diabetic nephropathy, three groups
      of sex-and age-matched patients were studied I) 22 insulin dependent diabetic
      (IDDM) patients with microalbuminuria (mean age +/- SEM: 23.3 +/- 3.6 years, mean
      urinary albumin excretion rate (AER) +/- SEM: 47.1 +/- 39.5 micrograms/min); II)
      17 IDDM patients with normoalbuminuria (mean age: 23.4 +/- 4.4 years, mean AER:
      7.8 +/- 2.1 micrograms/min) and III) 20 healthy control subjects (mean age: 22.6
      +/- 4.1 years, mean AER: 6.7 +/- 2.1 micrograms/min). PF and urinary excretion of
      albumin were measured by an immunoturbidimetric method using commercially
      available kits (Boehringer Mannheim GMBH FRG, and Miles Lab., UK). The mean PF
      was significantly higher in the group with microalbuminuria (406.5 +/- 122.9
      micrograms/ml) than in the group with normoalbuminuria (295.6 +/- 96.9
      micrograms/ml, P < 0.01) or in the control group (299.54 +/- 105.5 micrograms/ml,
      P < 0.01). A weak positive correlation was found between PF and urinary albumin
      values (r = 0.35, P < 0.05). There were no significant correlations between PF
      and the other variables such as age, duration of diabetes, body mass index,
      arterial blood pressure, fasting blood glucose, fructosamine and HbA1 in the
      diabetic patients or in the control group. Our results suggest that the PF
      concentration could be a weak marker for early diabetic nephropathy. We cannot
      therefore use PF instead of microalbuminuria because there is only a weak
      correlation between PF and microalbuminuria.

PMID- 7627277
TI  - [Catamenial migraine].

PMID- 7627278
TI  - [Estrogen-progestin agents].
AB  - Cardio-vascular pathology with estroprogestatives have justified an evolution of
      oral contraceptives of which the essential steps are the decrease of the posology
      in ethinylestradiol and the adjustment of new progestatives. This has allowed a
      decrease of thromboembolic risk and an improvement in the metabolic tolerance.
      The author, after having established an inventory of the products which exist on
      the French market calls for the prescription and the supervision of an
      estroprogestative contraception as well as reminds a certain number of practical
      advices.

PMID- 7627279
TI  - [Cytokines and reproduction: cybernetic aspects].

PMID- 7627280
TI  - [Preclinical trials for mastering intracytoplasmic injection of a sole
      spermatozoid for the treatment of male infertility].
AB  - Before starting with the clinical application of ICS, aged unfertilized oocytes
      were gathered for training and were injected with a single sperm or without a
      spermatozoon as a control group for activation. Oocyte damage, initially as high
      as 40% was reduced to 15% after 60 oocytes. Normal fertilization (2PN) occurred
      in 18% of the injected oocytes. After this training period 1,488 metaphase II
      oocytes collected during 144 cycles were used for ICSI. Results were split up in
      3 periods (n = 55, n = 24, n = 57) corresponding to the different improvements
      made in the technique. Results form ICSI in combination with MESA (n = 6) were
      analysed separately. Mean fertilization increased from 24% to 77%. Fertilization
      failures (18% of the cycles during the first period) vanished in the last period.
      Implantation rate improved from 7.4% to 11.4% and reached finally 26%. Pregnancy
      rate per oocyte retrieval was 16%, 25% and 54%. For the MESA group fertilization
      was 28%, implantation rate 17% and pregnancy rate 33% and only one fertilization
      failure was observed. A total of 50 pregnancies were obtained including 2
      obtained after MESA and 2 with cryopreserved embryos. Four healthy children are
      born, 9 were early abortions, 37 pregnancies are still on-going. Preclinical
      practice on aged unfertilized oocytes seems useful before starting with clinical
      ICSI, as high initial oocyte damage could be reduced and subsequent clinical
      treatment successfully applied. Offering high fertilization and pregnancy rates
      in cases of infertility with severe male factor it is extremely worthwhile
      mastering this new technique.

PMID- 7627281
TI  - [Prevention of breast cancer: what are the other possibilities under study
      besides tamoxifen chemoprevention?].
AB  - Tamoxifen and retinoids are actually studied for breast cancer chemoprevention.
      The role of fat intake, vitamins, selenium, alcohol consumption and progestins
      are reviewed in view of prevention trials.

PMID- 7627282
TI  - [Neurophysiology of perineal pain].
AB  - Perineal pains are based on two principal mechanisms: excess of nociception and
      desafferentation. The pain is psychogenic when none these mechanisms is found.
      Chronicization depends on first primary and secondary hyperalgesia and is
      sustained by sympathic and motor reflexs, and second nevrotic characters and even
      psychiatric pathology which give a painful experience of life.

PMID- 7627283
TI  - [Fertility after chronic, undiagnosed, ectopic pregnancy. A case observed during
      a myomectomy].
AB  - The authors report a case of a spontaneously absorbed ectopic pregnancy, that was
      fortuitously discovered during myomectomy in a 26 years old patient. She had been
      married for three years and had no child. She was seen 15 months later with a
      pregnancy whose outcome was safe through an elective cesarean section at 39 weeks
      of gestation. The authors emphasize the difficulties of early diagnosis of
      ectopic pregnancy in the context of a developing country.

PMID- 7627284
TI  - [Vulnerability of adolescents to sexually transmitted diseases].
AB  - Teenagers, and specially female teenagers, are vulnerable to STD on a threefold
      socioeconomic, epidemiologic and biologic level. The author discusses the causes
      and the outcomes of this issue.

PMID- 7627285
TI  - [Polycystic ovaries: an imprecise ultrasonographic definition].
AB  - In the absence of a precise definition, the terms "ovarian dystrophy" are often
      erroneously used. Therefore we propose a more modern terminology which allows to
      distinguish two types of ovarian follicle pathology: the microfollicular disease
      results from a follicular arrest of maturation, leading to an accumulation of
      immature microfollicles in the ovarian cortex. The clinical correlate is
      anovulation. This disease encompasses two aetiologic entities: polycystic ovarian
      disease (PCO) and the multifollicular ovaries (MFO), which were previously
      gathered under the label of "endocrinal ovarian dystrophy"; the macrofollicular
      disease results from the excessive growth of one or several follicles with or
      without luteinisation. Its clinical correlate is pelvic pain. It includes three
      main aetiologies: macropolycystic ovaries, functional cysts and LUF syndrome.
      These could also be termed "mechanical or local dystrophy". This new
      classification allows to consider two distinct anatomical entities which
      represent the whole of functional ovarian pathology.

PMID- 7627286
TI  - [Vaginal injuries during coitus: 98 cases].
AB  - We have undertaken a prospective study of vaginal injuries due to coitus with the
      aim of evaluating their incidence, risk factors and anatomic lesions. Over a
      period of 39 months, 98 cases were found, giving a monthly incidence of 2.5. The
      patients had a mean age of 25 years, were paucipara in more than 50%. Sexual
      abstience was found in 72 cases with a mean duration of 6 months. This injury
      occurred more often in gynecological period than in the postpartum (77 cases
      versus 22). During sexual intercourse the most harmful position was when the
      patient was in dorsal decubitus with maximum flexion and abduction of the limbs.
      The vaginal injury was located in the posterior cul de sac in 39 cases and was of
      5 cm of length in 56%. Surgical suture was required in 92 out of 98 patients, in
      combination with local and general antibiotics. CONCLUSION: Vaginal injuries due
      to coitus are frequent in our practice and they create serious anatomic lesions.
      So there is a need to precise the etiopathogenicity (hormonal deficiency ?,
      infections ?, role of the male partner) and to evaluate the long term sequellas.

PMID- 7627288
TI  - President's message: cultivating leaders.

PMID- 7627287
TI  - [History of sterility in ancient times. I. Sterility in Egypt. Diagnostic recipes
      for sterility and pregnancy in ancient Egypt].
AB  - Egyptians were the first to develop recipes in order to predict sterility and to
      diagnose an early pregnancy. These recipes was reused by Hippocrate and still
      employed until the XVIIIth century.

PMID- 7627289
TI  - Nursing diagnosis and specialty nursing practice.

PMID- 7627290
TI  - A descriptive study of the career mobility of ET nurses.
AB  - A qualitative study of the career mobility of ET nurses in the United States was
      conducted. Self-report questionnaires and demographic data sheets were mailed to
      a sample of 117 ET nurses, and the return response was 54.3%. Members of the
      study sample ranged in age from 29 to 58 years, and the range of duration of
      practice as an ET nurse was 1.5 to 18 years. The current positions of the
      respondents varied from staff nurse in a non-ET nurse role to director of
      marketing or education for manufacturers of wound, ostomy, and incontinence
      products. Practice sites were evenly distributed between industry and clinical.
      Analysis of self-report questionnaires and telephone interviews identified 30
      themes, which were reassessed for similarities and condensed to eight themes.
      These include consequences of the experience of being an ET nurse, precipitating
      event that resulted in a career change, ET nursing as a demarcation in practice,
      perception as currently practicing as an ET nurse, career mobility, feelings
      regarding ET nursing experiences, self-directedness in professional growth, and
      trajectory from clinical nursing to the business world.

PMID- 7627291
TI  - Marketing a hospital-based specialty program.
AB  - The 1980s were a time of growth and opportunity for hospital-based specialty
      programs. ET nurses developed a variety of highly valued clinics and services.
      Because of current trends toward downsizing, otherwise strong programs and
      services are undergoing unusual scrutiny. The purpose of this article is to offer
      the ET nurse ideas for strengthening hospital-based specialty programs through a
      marketing approach.

PMID- 7627292
TI  - Skin care for high-risk neonates.
AB  - Skin care for the high-risk neonate requires both knowledge of the unique aspects
      of the physiology of the integument of the neonate and awareness of potential
      complications. Practices that are useful in the prevention and treatment of skin
      complications among adults may be harmful when applied to neonates or young
      children. Although the focus of this article is on the neonate, iatrogenic
      complications have been reported in older children as well. Because a definitive
      age at which percutaneous absorption is no longer a risk is not known, it is best
      to err on the side of conservatism and apply these principles of neonatal skin
      care to the pediatric population at large.

PMID- 7627293
TI  - Putting pressure ulcers on the map.
AB  - Critical pathways are effective tools to coordinate care, decrease length of
      stay, and increase communication among health caregivers. This article presents a
      critical pathway for pressure ulcer management. The pathway is designed for use
      in a variety of settings, including acute care, home care, and extended care, to
      monitor and describe wound status and treatment regimens.

PMID- 7627295
TI  - Costs and management of urinary incontinence in long-term care.
AB  - The three aims of the study were (1) to assess the impact and cost of urinary
      incontinence in long-term care, (2) to determine whether 24-hour incontinence
      monitoring provides information that improves management, and (3) to ascertain
      whether costs (nursing time and laundry) could be reduced. The setting was two 24
      bed long-term care units in an urban hospital. The research was conducted in
      three stages. During the initial stage, the impact of incontinence was measured
      on each unit. Impact was defined as total number of incontinent episodes, nursing
      time spent changing these patients, and laundry costs, measured during a 7-day
      period on each unit. After this phase of the investigation, individualized 24
      hour incontinence monitoring, followed by recommendations and implementation of
      care plan, was carried out on one unit. No monitoring or recommendations for care
      were completed on the other unit, which served as a control. During the third
      phase of the study, the number of incontinent episodes, nursing time, and laundry
      costs were again measured on both units. Initially (58%) of residents (24/48)
      were incontinent, representing 859 episodes of urinary leakage each week that
      required 45 hours of nursing time to change clothing, containment devices, and
      bed linens. The direct costs of the nursing time and laundry, expressed in
      Canadian dollars were $8.60/day per incontinent resident. After 24-hour
      monitoring of 10 residents one on unit, suggestions were made for various
      incontinence management programs. An unexpected but simple recommendation was a
      change to a better containment system for urinary leakage. When impact was
      measured, a 13% reduction in the number of incontinent episodes was
      found.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7627294
TI  - Effects of incontinence care cleansing regimens on skin integrity.
AB  - Soap and water and a no-rinse cleanser, with and without a moisture barrier, were
      examined for their effects as cleansing regimens on the perineal skin of 10 older
      female residents of an extended care facility. Each cleansing regimen was used
      for 3 weeks, with two weekly measurements obtained for erythema, pH, and
      transepidermal water loss. Results indicated that soap and water was the least
      efficacious regimen unless used with a moisture barrier. The no-rinse cleanser
      was better than soap and water in terms of skin effects and cost savings. The
      findings suggest that a no-rinse cleanser in conjunction with a moisture barrier
      is a more skin-preserving and cost-effective incontinence care cleansing regimen
      than soap and water for older female nursing home residents with incontinence.

PMID- 7627296
TI  - Ileostomy stoma with mucocutaneous separation.

PMID- 7627297
TI  - Parents' perceptions of decision making for children.

PMID- 7627298
TI  - Baby K: medical futility and the free exercise of religion.

PMID- 7627299
TI  - The role of an ethics committee in resolving conflict in the neonatal intensive
      care unit.

PMID- 7627300
TI  - Forgoing medically provided nutrition and hydration in pediatric patients.

PMID- 7627301
TI  - Practice guidelines: how good are medicine's new recipes?

PMID- 7627302
TI  - Guidelines for clinical practice: what they are and why they count.

PMID- 7627303
TI  - From Baby Doe to Baby K: evolving challenges in pediatric ethics. Introduction.

PMID- 7627304
TI  - Practice guidelines and private insurers.

PMID- 7627305
TI  - Creating practice guidelines: the dangers of over-reliance on expert judgment.

PMID- 7627306
TI  - Practice guidelines: can they save money? Should they?

PMID- 7627307
TI  - One advocate's viewpoint: conflicts and tensions in the Baby K case.

PMID- 7627308
TI  - Can the development of practice guidelines safeguard patient values?

PMID- 7627310
TI  - Legal protections for the scientific misconduct whistleblower.

PMID- 7627309
TI  - Medical decision making and people with disabilities: a clash of cultures.

PMID- 7627311
TI  - Pleural malignant mesothelioma and non-occupational exposure to asbestos in
      Casale Monferrato, Italy.
AB  - OBJECTIVES: To assess and quantify the occurrence of pleural malignant
      mesotheliomas in people who neither experienced occupational exposure to asbestos
      nor were married to (or known to live with) workers exposed to asbestos in the
      workplace. The study was conducted in the area of the local health authority of
      Casale Monferrato, in north western Italy, where a large factory that produced
      asbestos cement was active up to 1985. No other major activities related to
      asbestos have ever been present in the area. METHODS: A retrospective survey
      covering the period 1980 to 1991 identified 126 incident pleural malignant
      mesotheliomas histologically diagnosed among residents in the local health
      authority (population at the 1981 census 98,000). Submission of 83 of 95 cases
      diagnosed during 1980-9 for revision by a panel of five expert pathologists led
      to the exclusion of 21. The 31 cases diagnosed in 1990-1 were not submitted for
      revision. For 64 of the 105 retained cases, information derived from different
      sources (rosters of the employees in the asbestos cement factory dated back to
      1907, list of their spouses, clinical records) did not suggest occupational or
      paraoccupational exposure to asbestos. RESULTS: Incidence excludes cases for
      which there was some suggestion of occupational or paraoccupational exposure to
      asbestos. Incidence of histologically confirmed malignant mesothelioma among
      residents in the local health authority (annual x 100,000; age adjusted) was 4.2
      in men and 2.3 in women (based on 26 and 18 cases respectively). In both sexes,
      rates in 1985-9 were higher than in the previous quinquennium. Corresponding
      estimates for 1990-1 (based on unrevised diagnoses) suggest similar rates in men
      and women. CONCLUSION: Rate ratios which are four to six times those measured by
      conventional Italian cancer registries can hardly be totally explained by bias
      produced by lack of recognition of occupational or paraoccupational exposure. The
      problem of proving this type of negative data is common to other circumstances of
      alleged cancer clusters of environmental (non occupational) origin.

PMID- 7627312
TI  - Decline in annual lung function in workers exposed to asbestos with and without
      pre-existing fibrotic changes on chest radiography.
AB  - OBJECTIVES: To examine whether or not workers with pre-existing mild pulmonary
      fibrosis have accelerated decline in forced expiratory volume in one second
      (FEV1) or forced vital capacity (FVC), under low level exposure to chrysotile
      asbestos. METHODS: All male workers in two asbestos manufacturing factories were
      followed up annually for six years to compare their declines in FEV1 and FVC. The
      values of FEV1 and FVC were divided by the square of the person's height to
      adjust for body size differences (FEV1/Ht2 and FVC/Ht2, respectively). Annual
      change was calculated for each subject as a slope of the simple linear regression
      with FEV1/Ht2 or FVC/Ht2 regressed according to age. Analysis was conducted on
      242 middle aged workers who had normal routine spirometry values, normal chest
      radiographs or mild pneumoconiosis up to 1/2 grade, without changes either in
      smoking habit or severity of pneumoconiosis during the study period, and with
      acceptable spirograms in three or more surveys. The occupational environment, in
      terms of chrysotile asbestos, had been well controlled below the threshold limit
      value of Japan at that time--namely, 2 fibres/micromilligrams. RESULTS-There was
      no significant effect from the interaction between pre-existing mild pulmonary
      fibrosis and low level of exposure to chrysotile asbestos on the accelerated
      annual decline of FEV1/Ht2, or FVC/Ht2. Fibrosis significantly contributed to
      annual changes in FEV1/Ht2, even after adjustment for mean FEV1 and smoking. The
      point estimate of the contribution was - 4.9 ml/m2/y. No significant independent
      contribution of exposure was found in decline of either FEV1/Ht2 or FVC/Ht2.
      CONCLUSIONS: Pre-existing pulmonary fibrosis is an independent risk factor for
      accelerated annual decline of FEV1, even when mild and stable. Additional decline
      due to exposure to chrysotile asbestos is less probable if it is well controlled
      under the current threshold limit value.

PMID- 7627313
TI  - Chronic lymphocytic leukaemias and non-Hodgkin's lymphomas by histological type
      in farming-animal breeding workers: a population case-control study based on job
      titles.
AB  - OBJECTIVES: A population based case-control study was conducted in a highly
      agricultural area in the north east of Italy to evaluate the association between
      farming and animal breeding and the risk of developing non-Hodgkin's lymphoma
      (NHL) and chronic lymphocytic leukaemia (CLL). METHODS: Occupational histories
      and other data were collected by personal interview on 164 NHLs, 23 CLLs,
      diagnosed in 1988-90, and on 977 controls. This paper only reports the results of
      the analysis relative to the coding of job titles through the modified
      International Labour Office (ILO) classification. Estimates of odds ratios (ORs)
      for occupational variables were calculated, after adjustment for sex, age,
      altitude of municipality, first degree familiarity, and previous Herpes zoster
      infection. RESULTS: From the analysis of the most frequent occupational
      categories, no occupation showed a significantly high risk. When the two job
      titles farmers only and farmer-breeders who are also involved in animal breeding
      are classified within the extremely varied occupation of agriculture or animal
      breeding or fishing, a high risk for NHLs and CLLs is seen in the farmer-breeders
      (OR 1.79, 95% CI 1.22 - 2.63). Analyses according to histological type show that
      the risks are concentrated in CLLs and in low grade NHLs. No effect or trend by
      period at work or duration of employment in farming and animal breeding was
      found. CONCLUSION: Subjects working in agriculture associated with animal
      breeding are at high risk of NHL/CLLs, particularly CLLs and low grade NHLs. This
      finding could be related to the use of chemicals in agriculture or to exposure to
      animal transmitted diseases or specific chemicals used in animal breeding.

PMID- 7627314
TI  - Risk of acute myeloid leukaemia and multiple myeloma in workers exposed to
      benzene.
AB  - OBJECTIVE: To determine the risk of developing acute myeloid leukaemia (AML) and
      multiple myeloma in a cohort of workers exposed to benzene. The results were used
      to show the importance of taking specificity of disease into consideration in
      causation analysis. METHODS: Data were derived from a cohort of workers employed
      at two Goodyear plants in Ohio in the manufacture of Pliofilm. Based on data in
      the Pliofilm study, several papers that examined the relation between exposure to
      benzene and leukaemia (all cell types combined) have been published. In the
      current analyses based on updated data in the study, standardised mortality
      ratios (SMRs) and 95% confidence intervals (95% CIs) were calculated for AML and
      multiple myeloma by cumulative exposure to benzene. The results based on AML were
      compared with those for leukaemia (all cell types combined) published previously.
      RESULTS: An exposure response relation was shown between cumulative exposure to
      benzene and AML. No increased risk of AML was detected for cumulative exposure to
      benzene below 200 ppm-years (SMR 0.91). Above 200 ppm-years, risk of AML rose
      drastically; reaching a significant SMR of 98.37 for > 400 ppm-years. For
      multiple myeloma, no relation with exposure to benzene was detected. CONCLUSION:
      Analysis specific to AML shows the importance of taking specificity of disease
      into consideration in causation analysis. This investigation shows that previous
      analyses based on all leukaemia cell types combined have incorrectly set the
      estimated threshold too low, and have underestimated risk above the threshold.
      Current regulatory policies that rely on previous analyses based on all leukaemia
      cell types combined should be re-examined.

PMID- 7627315
TI  - Dioxin concentrations in the blood of workers at municipal waste incinerators.
AB  - OBJECTIVES: Increased concentrations of polychlorinated dibenzo-p-dioxins (PCDDs)
      and polychlorinated dibenzo-furans (PCDFs) in pooled blood samples from workers
      at municipal waste incinerators have been reported. This study was undertaken to
      confirm these results in individual blood samples from potentially exposed and
      unexposed workers at municipal waste incinerators compared with matched unexposed
      controls and compared with concentrations in the slag and fly ash from the
      municipal waste incinerators. METHODS: Concentrations of PCDDs and PCDFs were
      determined in the blood of 10 workers from an old municipal waste incinerator
      without adequate pollution controls, 11 workers from a newer incinerator with
      modern pollution controls, and 25 controls from the general population group
      matched for age (+/- 10 years), sex, and race, and in the slag and fly ash from
      the older incinerator. RESULTS: Significant increases of certain PCDDs and PCDFs
      were found in the blood of the workers from the older incinerator compared with
      the controls as follows: octaCDD (1051 (438) v 637 (344), P < 0.001), hexaCDF
      (52.3 (28.7) v 30.2 (18.2), P < 0.01), heptaCDF (43.9 (30.4) v 22.7 (12.4), P <
      0.001), total PCDDs (1262 (484) v 825 (454), P < 0.001), total PCDFs (133.0
      (68.1) v 93.7 (36.7), P < 0.05), and total PCDD/Fs (1395 (537) v 918 (437), P <
      0.001). The workers from the older incinerator with the greatest exposure were
      found to have the most significant increases of the blood PCDDs and PCDFs, and
      the pattern of increased PCDD and PCDF congeners in the blood corresponded to the
      pattern in the incinerator slag and ash. No significant differences were found
      between the blood concentrations of the workers at the newer incinerator and the
      controls. CONCLUSION: Occupational exposure to slag and fly ash from municipal
      waste incinerators may increase the blood concentrations of PCDDs and PCDFs.
      Modern pollution control technology in new incinerators may be able to minimise
      potential exposure to slag and fly ash and thus the absorption of PCDDs and PCDFs
      from this source.

PMID- 7627316
TI  - Asthmatic symptoms and volatile organic compounds, formaldehyde, and carbon
      dioxide in dwellings.
AB  - OBJECTIVES: As a part of the worldwide European Community respiratory health
      survey, possible relations between symptoms of asthma, building characteristics,
      and indoor concentration of volatile organic compounds (VOCs) in dwellings were
      studied. METHODS: The study comprised 88 subjects, aged 20-45 years, from the
      general population in Uppsala, a mid-Swedish urban community, selected by
      stratified random sampling. Room temperature, air humidity, respirable dust,
      carbon dioxide (CO2), VOCs, formaldehyde, and house dust mites were measured in
      the homes of the subjects. They underwent a structured interview, spirometry,
      peak expiratory flow (PEF) measurements at home, methacholine provocation test
      for bronchial hyperresponsiveness, and skin prick tests. In addition, serum
      concentration of eosinophilic cationic protein (S-ECP), blood eosinophil count,
      and total immunoglobulin E (S-IgE) were measured. RESULTS: Symptoms related to
      asthma were more common in dwellings with house dust mites, and visible signs of
      dampness or microbial growth in the building. Significant relations were also
      found between nocturnal breathlessness and presence of wall to wall carpets, and
      indoor concentration of CO2, formaldehyde, and VOCs. The formaldehyde
      concentration exceeded the Swedish limit value for dwellings (100 micrograms/m3)
      in one building, and CO2 exceeded the recommended limit value of 1000 ppm in 26%
      of the dwellings, showing insufficient outdoor air supply. Bronchial
      hyperresponsiveness was related to indoor concentration of limonene, the most
      prevalent terpene. Variability in PEF was related to two other terpenes; alpha
      pinen and delta-karen. CONCLUSION: Our results suggest that indoor VOCs and
      formaldehyde may cause asthma-like symptoms. There is a need to increase the
      outdoor air supply in many dwelling, and wall to wall carpeting and dampness in
      the building should be avoided. Improved indoor environment can also be achieved
      by selecting building materials, building construction, and indoor activities on
      the principle that the emission of volatile organic compounds should be as low as
      reasonably achievable, to minimise symptoms related to asthma due to indoor air
      pollution.

PMID- 7627317
TI  - Effect of different exposure compounds on urinary kinetics of aluminium and
      fluoride in industrially exposed workers.
AB  - OBJECTIVE: To conduct a field study to obtain information on the urinary
      concentrations of aluminium (Al) and fluoride (F-) depending on the different
      compounds exposed to in the aluminum industry. METHODS: 16 workers from one plant
      that produced aluminium fluoride (AlF3), and from two plants that produced
      aluminium electrolytically by two different processes participated in the study
      for one working week. Pollutants were monitored by eight hour personal sampling
      every day, and urine samples were collected during the week. Al and F- were
      analysed in both atmospheric and urine samples by atomic absorption spectrometry
      and an ion selective electrode. RESULTS: The principal results show different
      characteristics of kinetic curves of Al and F- excretion in workers with
      different exposures. Some characteristics of excretory peaks were linked to
      specific exposures--for instance, after exposure to AlF3 there was one delayed Al
      peak associated with one delayed F- peak about eight hours after the end of the
      daily shift, and after mixed exposure to HF and AlF3, two F- peaks were noted,
      one fast peak at the end of the shift and another delayed peak at 10 hours
      synchronised with an Al peak. In one of the electrolysis plants, the exposure to
      Al and F- compounds led to the simultaneous excretion of Al and F- peaks, either
      as a single peak or two individual ones depending on the type of technology used
      on site (open or enclosed potlines). The average estimated half life of Al was
      7.5 hours, and of F- about nine hours. Quantitative relations between excretion
      and exposure showed an association between the F- atmospheric limit value of 2.5
      mg/m3 with a urinary F- concentration of 6.4 mg/g creatinine at the end of the
      shift, a peak of 7.4 mg/g creatinine, and 7.4 mg excreted a day. For Al, the
      exposure to 1.36 mg/m3 during the shift corresponded to a urinary concentration
      at the end of the shift of 200 microgram/g creatinine. Daily excretion of 200
      micrograms corresponded to an exposure to 0.28 mg/m3. CONCLUSION: Particular
      differences in the behaviour of Al and F- in urine depended upon the original
      molecular form in the pollutant. These results reinforce the principle that, in
      biological monitoring, the sampling strategy and the choice of limit value should
      be dependent on kinetic data that take the exposure compound of the element in
      question into account.

PMID- 7627318
TI  - Polyneuropathy induced by carbon disulphide in viscose rayon workers.
AB  - OBJECTIVES: To understand the prevalence of polyneuropathy and correlations among
      the clinical manifestations, electrophysiological findings, and degree of
      exposure to carbon disulphide (CS2) in workers who were exposed to variable
      concentrations of CS2 in a viscose rayon factory. METHODS: All the 163 workers
      received a detailed physical and neurological evaluation. Fixed point air samples
      were analysed for CS2. Nerve conduction velocity was studied in 26 workers with
      symptoms similar to neuropathy. RESULTS: Nine workers (53%) with overt
      polyneuropathy from the fibre cutting department and 19 workers (13%) with
      oligosymptoms similar to polyneuropathy from various jobs were noted. The fixed
      point air concentrations of CS2 were 150-300 ppm in the cutting areas and 15 to
      100 ppm in the spinning areas. The estimated eight hour time weighted averages in
      the fibre cutting areas were 40-67 ppm. The occurrence of polyneuropathy was
      generally correlated with the degree of exposure to CS2. Nerve conduction
      velocities (NCVs) were significantly different in the overt polyneuropathy and
      subclinical polyneuropathy groups from the normal controls. The sensitive
      indicators for CS2 polyneuropathy were distal latency, motor NCV, and amplitude
      of sensory nerve action potentials in sensory NCVs. CONCLUSION: The outbreak of
      polyneuropathy was attributed to higher concentrations of CS2 in fibre cutting
      areas. Even in other jobs with relatively lower concentrations of CS2, the hazard
      of subclinical polyneuropathy cannot be overlooked.

PMID- 7627320
TI  - Combined electroneurographic and electromyographic studies in lead workers.
AB  - OBJECTIVES: To evaluate the effects of chronic exposure to lead on the peripheral
      nervous system in lead workers. METHODS: Nerve conduction velocity and
      electromyographic studies were performed on 31 lead workers of a battery
      recycling factory and 31 sex and age matched controls. 25 cases with mild distal
      extensor weakness of the upper limbs were classified as the lead neuropathy
      subgroup and the rest of the lead workers as the lead exposure subgroup. Blood
      lead concentrations and haematological and biochemical data were recorded. An
      index of cumulative exposure to lead was calculated by the summation of
      multiplying the average blood concentration of lead with the duration of exposure
      at various jobs. RESULTS: Compared with the control group, the distal motor
      latency of the median nerve was significantly prolonged in the lead neuropathy
      subgroup, but not in the exposure subgroup. Only six of 31 workers had nerve
      conduction abnormalities, whereas electromyographic evidence of denervation was
      found in 93.5% of the lead neuropathy subgroup and 83.5% in the lead exposure
      subgroup. The electromyographic abnormalities found were neurogenic polyphasic
      waves in all 29 workers with abnormal electromyographic findings (grade in seven
      cases and grade ++ in the rest). Spontaneous activity was only recorded in seven
      workers, with grade + in four and grade ++ in three. There was a positive linear
      correlation between the index of cumulative exposure to lead and the distal motor
      latencies of the tibial nerve as well as a negative correlation with conduction
      velocities of the sural nerve after multivariate analysis and control of
      potential confounding by age and sex. No correlation could be found between the
      electrophysiological values and a simple duration of exposure or concentration of
      blood lead. A non-parametric analysis showed that there was a trend of higher
      index of cumulative exposure to lead with more severe electromyographic changes.
      Electromyographic abnormality also occurred in workers with blood lead
      concentrations between 17.4 and 58 micrograms/dl. CONCLUSION: Electromyographic
      study in the distal extensors of the upper limbs may be used as a tool for
      biological monitoring of effect in lead workers.

PMID- 7627319
TI  - Neurobehavioural evaluation of Venezuelan workers exposed to inorganic lead.
AB  - OBJECTIVES: To assess neurobehavioural effects of low exposure to lead, 43
      workers from a lead smelter and 45 workers from a glass factory were evaluated
      with the World Health Organisation neurobehavioural core test battery (NCTB) in a
      cross sectional study. METHODS: The NCTB comprises a questionnaire and seven
      tests that measure simple reaction time, short-term memory (digit span, Benton),
      mood (profile of mood states), eye-hand coordination (Santa Ana pegboard, pursuit
      aiming II), and perceptual speed (digit-symbol). RESULTS: Smelter workers were
      employed on average for four years, and had a mean blood lead concentration of
      2.0 mumol/l (42 micrograms/dl). Glass factory workers had a mean of 0.72 mumol/l
      (15 micrograms/dl). Historical blood lead concentrations were used to classify
      exposure based on current, peak, and time weighted average. Although the exposed
      workers performed less well than the non-exposed in 10 of 14 response variables,
      only profile of mood states tension-anxiety, hostility, and depression mood
      scales showed a significantly poorer dose-response relation with blood lead
      concentration in multiple linear regression models that included age, education,
      and alcohol intake as covariates. The frequency of symptoms of anger, depression,
      fatigue, and joint pain were also significantly increased in the exposed group.
      CONCLUSION: This study is consistent with the larger body of neurobehavioural
      research of low occupational exposure to lead. The small effects found in this
      study occurred at blood lead concentrations slightly lower than those reported in
      several previous studies.

PMID- 7627322
TI  - Offspring sex ratio as an indicator of reproductive hazards associated with
      pesticides.

PMID- 7627321
TI  - Determination of low level exposure to volatile aromatic hydrocarbons and
      genotoxic effects in workers at a styrene plant.
AB  - OBJECTIVES: Low exposures to volatile aromatic hydrocarbons and cytogenetic
      effects in peripheral white blood cells were determined in 25 healthy workers
      employed in different areas of a styrene production plant in the former German
      Democratic Republic. The results were compared with 25 healthy unexposed controls
      (matched for age and sex) employed in the same company. METHODS: The
      concentrations of aromatic hydrocarbons determined from active air sampling in
      all areas of the factory (styrene: 73-3540 micrograms/m3 (< 0.01-0.83 ppm);
      ethylbenzene 365-2340 micrograms/m3 (0.08-0.53 ppm); benzene 73-3540
      micrograms/m3 ( < 0.02-1.11 ppm); toluene 54-2960 micrograms/m3 (0.01-0.78 ppm);
      xylenes 12-94 micrograms/m3 ( < 0.01-0.02 ppm)) were considerably lower than in
      the pump house ( > 4000 micrograms/m3 styrene, ethylbenzene, benzene, and
      toluene; > 500 micrograms/m3 xylenes), which was only intermittently occupied for
      short periods. Passive personal monitoring, biomonitoring of exhaled air and
      metabolites (mandelic, phenylglyoxylic, trans, trans-muconic, hippuric, o-, m-
      and p-methylhippuric acids, and phenol) in urine samples collected before and
      after an eight hour working shift was used to assess individual exposure.
      Questionnaires and examination of company records showed that the historical
      exposure was far higher than that measured. Genotoxic monitoring was performed by
      nuclease P1-enhanced 32P-postlabelling of DNA adducts in peripheral blood
      monocytes, and DNA single strand breaks, sister chromatid exchange, and
      micronuclei in lymphocytes. The content of kinetochores in the micronuclei was
      determined by immunofluorescence with specific antibodies from the serum of CREST
      patients. RESULTS: No genotoxic effects related to exposure were detected by DNA
      adducts or DNA single strand breaks and sister chromatid exchange. The only
      effect related to exposure was an increase in kinetochore positive micronuclei in
      peripheral lymphocytes; the frequency of total micronuclei in peripheral
      lymphocytes did not change. Smoking was confirmed by measurement of plasma
      cotinine, and no confounding effect was found on any of the cytogenetic
      variables. CONCLUSIONS: Low occupational exposure to styrene, benzene, and
      ethylbenzene did not induce alterations of genotoxicological variables except
      kinetochore positive micronuclei. This is the first reported use of the CREST
      technique for an in vivo study in occupational toxicology, which thus could serve
      as a valuable and sensitive technique for toxicogenic monitoring.

PMID- 7627324
TI  - ANJ interviews Marea Vidovich. Interview by Amanda Tattam.

PMID- 7627323
TI  - ANJ interviews Marilyn Beaumont. Interview by Leena Sudano.

PMID- 7627325
TI  - Cervical screening.

PMID- 7627327
TI  - Understanding rostering. Part 2. The rights & wrongs of rostering.

PMID- 7627326
TI  - Being our age: older women's voices.

PMID- 7627328
TI  - You're not 'just a nurse': that is why we are not just a union.

PMID- 7627329
TI  - Nursing and the law. Deadly doses of methotrexate.

PMID- 7627330
TI  - Nursing process: more hype than help?

PMID- 7627331
TI  - Comparative effects of food restriction, fasting, diabetes and thyroidectomy on
      growth hormone and thyrotropin gene expression in the rat pituitary.
AB  - To examine the molecular basis for the decreased pituitary growth hormone (GH)
      and thyrotropin (TSH) content during restricted feeding, fasting and diabetes, we
      measured steady-state levels of mRNA for TSH-alpha, TSH-beta and GH in the
      pituitary from normal rats either fed ad libitum (C), limited to 75%, 50% and 25%
      (FR75, FR50, FR25, respectively) of ad libitum intake, or deprived of food for 2
      and 4 days (F2 and F4, respectively), and also in streptozotocin-diabetic (D) and
      D insulin-treated animals. The results from these experimental groups were
      compared with those in thyroidectomized (Tx) rats. Pituitary mRNA was quantified
      by Northern blot hybridization with cDNA probes specific for rat TSH-alpha, TSH
      beta and GH. Although changes in the pituitary GH mRNA during restricted feeding,
      fasting and diabetes were similar qualitatively to those induced by
      hypothyroidism, GH mRNA levels in Tx rats (> 10% of C values) were less than in
      the other experimental groups (p < 0.001). Pituitaries from FR50, FR25 and D rats
      also contained less GH mRNA than F2 and F4 animals (p < 0.05). Thyroidectomy
      resulted in a marked increase in both TSH-beta and TSH-alpha mRNAs, the changes
      in TSH-beta mRNA being greater than those in TSH-alpha mRNA. In contrast, FR50,
      FR25, F2, F4 and D rats exhibited a decrease in pituitary TSH-beta mRNA (60%,
      50%, 35%, 36% and 33%, respectively, of C values; p < 0.01-0.05) and in TSH-alpha
      mRNA levels (81%, 64%, 46%, 43% and 36%, respectively, of normal values; p < 0.02
      0.05), TSH-beta mRNA showing the greater changes.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7627332
TI  - Growth hormone (GH)-releasing heptapeptide, but not GH-releasing hormone,
      inhibits thyrotropin-stimulated thyroid hormone secretion and cAMP formation in
      cultured human thyroid follicles.
AB  - Synthetic heptapeptide growth hormone-releasing peptide-1 (GHRP-1) potently
      stimulates GH release in many species, including humans. We investigated the
      direct in vitro effect of this peptide, compared to growth hormone-releasing
      hormone (GHRH), on cultured human thyroid follicles. The results indicate that
      whereas GHRP-1 (6-600 micrograms/l) or GHRH (6-600 micrograms/l) alone had no
      effect on basal triiodothyronine (T3) secretion or cAMP formation, the
      heptapeptide (6-600 micrograms/l), but not GHRH (6-1200 micrograms/l), dose
      dependently inhibited thyrotropin (TSH)-stimulated T3 secretion and cAMP
      formation. Moreover, GHRP-1 also dose-dependently inhibited forskolin-stimulated
      T3 secretion. It would seem, therefore, that the GHRP-1-induced inhibitory effect
      on thyroid function is located downstream of cAMP formation, without necessarily
      excluding an additional inhibitory action at a pre-cAMP site. These results
      additionally demonstrate differences in the mode of action of GHRP-1 and GHRH.

PMID- 7627333
TI  - Dexamethasone-induced changes in glucose transporter 4 in rat heart muscle,
      skeletal muscle and adipocytes.
AB  - To clarify the effect of glucocorticoid on glucose transporters (GLUT) in
      adipocytes and muscle, we examined the changes of GLUT4 in rat heart muscle,
      skeletal muscle and adipocytes during long-term administration of dexamethasone
      and the translocation of GLUT4. The levels of GLUT4 in the plasma membrane and
      the low-density microsome fraction were measured by Western blotting using anti
      GLUT4 peptide antibody. The levels of GLUT4 in the heart and skeletal muscles of
      rat were unchanged by treatment of dexamethasone. In the adipocytes the level of
      GLUT4 in plasma membrane was changed, but it was decreased in the low-density
      microsome fraction. Although adipocytes are less involved in blood sugar
      regulation than skeletal muscle, this finding suggests that glucose metabolism in
      Cushing's syndrome is affected partly by a decrease of GLUT4 in the adipocytes.

PMID- 7627335
TI  - Calcitonin, calcitonin gene-related peptide, adrenomedullin and amylin:
      homologous peptides, separate receptors and overlapping biological actions.
AB  - Calcitonin, calcitonin gene-related peptide, adrenomedullin and amylin are
      structurally related peptides with N-terminal 6-7 amino acid ring structures
      linked by a disulfide bridge and with amidated C-termini. Among the related
      bioactive peptides, the structures of the calcitonin receptor and subtypes
      thereof have been identified so far through molecular cloning. Cross-reaction
      between receptors of calcitonin, calcitonin gene-related peptide, adrenomedullin
      and amylin, as well as overlapping biological actions, anticipate that the
      respective receptors belong to a family of G-protein-coupled receptors that
      include those of parathyroid hormone, secretin and vasointestinal peptide.

PMID- 7627334
TI  - Effects of V1- and V2-vasopressin (AVP) antagonists on the pressor, AVP and
      atrial natriuretic peptide responses to a hypertonic saline infusion in conscious
      anephric rats.
AB  - To examine the role of vasopressin (AVP) receptors in the regulation of the
      hemodynamics and release of atrial natriuretic peptide (ANP), and the
      participation of renal nerve inputs in the osmotic AVP release, hypertonic saline
      (HS) was infused into conscious, bilaterally nephrectomized rats with non
      peptide, selective antagonists for the V1-receptor or V2-receptor of AVP. In the
      control group, HS alone increased mean arterial pressure, plasma ANP and AVP,
      plasma volume and plasma osmolality, and decreased the heart rate. In the V1
      receptor antagonist group, an increase in the mean arterial pressure and a
      decrease in heart rate were completely abolished and an increase in plasma ANP
      was attenuated. In the V2-receptor antagonist group, increases in mean arterial
      pressure and plasma ANP and a decrease in heart rate were attenuated. However,
      the ratio of the changes in heart rate to the changes in mean arterial pressure
      in the V2-receptor antagonist group is significantly higher than that in the
      control group. In both experimental groups, increases in plasma AVP, plasma
      volume and plasma osmolality were not different from those in the control group.
      These results suggest that a HS-induced increase in mean arterial pressure is
      mediated by the pressor effect of AVP, mainly through V1-receptors, and that the
      depressor effect of AVP through V2-receptors may not influence tonically HS
      induced hypertension. Moreover, HS-induced increase in plasma ANP is mediated
      mainly by increases in plasma volume and blood pressure, but may not be affected
      by a direct action of AVP to the heart. Renal afferent nerve inputs may not have
      effects on the regulation of osmotic AVP release.

PMID- 7627336
TI  - Technetium-99m pentavalent dimercaptosuccinic acid imaging in patients with
      pituitary adenomas.
AB  - We studied the tumor-seeking agent technetium-99m-labeled pentavalent
      dimercaptosuccinic acid ([99mTc](V)DMSA) to visualize 21 growth hormone (GH)-,
      nine prolactin (PRL)-, two mixed GH/PRL-, six adrenocorticotrophin (ACTH)
      secreting and 15 clinically non-functioning pituitary adenomas, three
      craniopharyngiomas and one dysgerminoma of the sella. All non-adenomas and 31 out
      of 53 adenomas were studied before treatment: 22 after surgery and/or
      radiotherapy. Eight cases of acromegaly were studied before and after chronic
      treatment with octreotide, whereas three cases of acromegaly, one of prolactinoma
      and two of non-functioning adenoma were imaged before and after adenomectomy. As
      a control group, 27 patients without any clinical evidence of pituitary adenoma
      were studied: 10 of them were operated on previously and treated with iodine-131
      for metastatic thyroid carcinoma, 10 had brain tumors and the remaining seven
      patients had functional pituitary hypersecretion (four Klinefelter's syndrome,
      two primary hypothyroidism and one Addison's disease). The scintigraphy was
      repeated after testosterone in Klinefelter's syndrome, L-thyroxine in primary
      hypothyroidism and cortisone administration in Addison's disease. Seventeen GH
      secreting (81%), seven PRL-secreting (78%), three ACTH-secreting (50%), 15 non
      functioning (100%) and one (50%) mixed adenoma significantly concentrated
      [99mTc](V)DMSA, showing elevated tumor-to-background (T/B) ratios. The T/B ratios
      were similar in untreated and surgically treated adenomas (11.2 +/- 5.6 vs 11.8
      +/- 6.2). Radiotherapy significantly lowered the [99mTc](V)DMSA uptake to 5.1 +/-
      2.8 (p < 0.1 vs untreated patients). Non-adenomatous lesions of the sella turcica
      did not concentrate [99mTc](V)DMSA in the pituitary as well as brain tumors and 8
      out of 10 metastatic thyroid cancers. The treatment with octreotide normalized GH
      and insulin-like growth factor I levels and reduced [99mTc](V)DMSA from 15.7 +/-
      4.8 to 13.5 +/- 3.9 (p < 0.05). Conversely, adequate substitutive therapy
      completely inhibited the uptake of the radiotracer in Klinefelter's syndrome, in
      primary hypothyroidism and in Addison's disease. The [99mTc](V)DMSA scintigraphy
      showed an overall sensitivity of 81% (43/53) in detecting pituitary adenomas,
      which was increased to 95% for lesions greater than 10 mm in size. High-quality
      images with minimal total body radiation were obtained, enabling a good in vivo
      characterization of viable adenomatous tissue as well as an accurate monitoring
      of the effects of different therapeutic regimens.

PMID- 7627338
TI  - Hormonal serum profiles and follicular development after intramuscular and
      pulsatile intravenous administration of human menopausal gonadotrophin.
AB  - A study was performed to compare, in a randomized way, the effect of pulsatile
      intravenous (i.v.) and intramuscular (im) human menopausal gonadotrophin (hMG)
      administration on hormonal serum profiles and follicular development in in vitro
      fertilization (IVF). Fourteen IVF patients participated in the study, aged
      between 20 and 40 years, with a normal endocrine profile, no hormonal medication
      used for at least 3 months previously, no endometriosis, both ovaries present and
      a normal male factor. Seven patients were treated with im hMG at a daily dose of
      150 IU and seven patients with pulsatile i.v. hMG at a daily dose of 112.5 IU, in
      both cases in combination with buserelin. Ultrasonography was performed every
      other day during the stimulation phase and blood samples were collected once
      daily up to five times a day during the entire IVF cycle. Serum concentrations of
      follicle-stimulating hormone, luteinizing hormone, 17 beta-oestradiol,
      progesterone and human chorionic gonadotrophin were determined. There were no
      differences in hormonal profiles between the two groups. The numbers of retrieved
      oocytes, fertilization rates and mean embryo quality were identical in this
      study, as was follicular growth. In conclusion, in the present randomized study
      no differences were observed in hormonal levels or follicular development after
      im and pulsatile i.v. hMG treatment.

PMID- 7627339
TI  - Paracrine role for calcitriol in the immune system and skin creates new
      therapeutic possibilities for vitamin D analogs.

PMID- 7627337
TI  - Delayed puberty in males with beta-thalassemia major: pulsatile gonadotropin
      releasing hormone administration induces changes in gonadotropin isoform profiles
      and an increase in sex steroids.
AB  - Patients with beta-thalassemia major often have pubertal delay, the etiology of
      which has not been fully elucidated. We investigated the pituitary-gonadal
      response to short-term subcutaneous pulsatile gonadotropin-releasing hormone
      (GnRH) administration (150 ng/kg body weight every 120 min for 7 days) in five
      young males (aged 13.6-19.0 years) affected by beta-thalassemia major and
      presenting signs of delayed puberty. Immunoreactive and bioactive gonadotropin
      levels were determined and their isoform profiles were examined, before and after
      GnRH treatment, in a pool of samples collected every 15 min for 240 min.
      Testosterone, androstenedione, 17-hydroxyprogesterone, dehydroepiandrosterone and
      17 beta-estradiol were measured as markers of gonadal function on days 0, 1, 3, 5
      and 7 of treatment. Five patients (aged 16.9-26.8 years) with confirmed diagnosis
      of idiopathic hypogonadotropic hypogonadism who were starting pulsatile GnRH
      therapy were also studied in the same protocol. Increased sex steroid levels were
      observed in both groups as a result of treatment. On day 7, the thalassemic
      patients had increased bioactive luteinizing hormone (LH) and follide-stimulating
      hormone (FSH), although immunoreactive LH and FSH were comparable to day 0.
      Moreover, fewer acidic and more basic immunoreactive and bioactive isoforms were
      noted in LH profiles on day 7. Similar results were observed in hypogonadal
      patients, who also had increased immunoreactive LH and FSH values. We suggest
      that the early stage of delayed puberty in thalassemia might be characterized by
      a neuroendocrine dysfunction resulting in an impaired hypothalamic GnRH release,
      which is inadequate for a proper pituitary stimulation. Pulsatile GnRH treatment
      seems to re-establish partially the correct pituitary-gonadal function.

PMID- 7627341
TI  - Influence of meal composition on the postprandial response of the pituitary
      thyroid axis.
AB  - Ingestion of food can result in an acute decline of serum thyrotropin (TSH)
      concentrations, but it is not known whether meal composition and/or stomach
      distension are influential. Normal men and women were given a normocaloric or
      hypocaloric, isobulk meal at lunch and at dinner in a randomized design. The
      normocaloric, but not the isobulk, meal resulted in a significant decline in
      serum TSH at both lunch and dinner; thyroid hormones and cortisol were not
      affected significantly. These findings suggest that meal composition is
      influential in the acute postprandial decline of serum TSH in man. A possible
      mechanism is food-induced elevation of somatostatin and consequent suppression of
      TSH secretion.

PMID- 7627340
TI  - Circadian thyrotropin variations are preserved in normal pregnant women.
AB  - Serum thyrotropin (TSH) concentration circadian rhythm is abolished in many
      endocrine and non-endocrine diseases. In the present study we have measured serum
      TSH concentration over 24 h every 2 h in second and third trimester pregnant
      women. During the 24-h period, serum free thyroxine and free triiodothyronine
      concentrations did not change significantly. In contrast, serum TSH
      concentrations demonstrated significant circadian variations both in the second
      and third trimester pregnant women (p < 0.02 and p < 0.005, respectively). In
      summary, second and third trimester pregnancy is associated with a normal
      circadian TSH rhythm.

PMID- 7627342
TI  - Clinical usefulness of thyroid-stimulating antibody measurement using Chinese
      hamster ovary cells expressing human thyrotropin receptors.
AB  - Human thyrotropin (TSH) receptors were expressed in Chinese hamster ovary (CHO)
      cells using eukaryotic expression plasmid pCXN2, which contains beta-actin
      promoter. We measured cAMP stimulation in CHO cells expressing human TSH
      receptors (CHO-hTSH-R cells) by immunoglobulin G (IgG) of patients with Graves'
      disease and Hashimoto's thyroiditis, and compared the results with a conventional
      thyroid-stimulating antibody (TS-Ab) assay using porcine thyroid cells and a TSH
      binding inhibiting immunoglobulin (TBII) assay. Nineteen untreated patients with
      Graves' disease, including a case who developed hyperthyroidism after interferon 
      alpha therapy for chronic hepatitis C, and 13 treated patients with Graves'
      disease, 10 patients with Hashimoto's thyroiditis and 8 control subjects were
      studied. In 19 untreated patients with Graves' disease, 17 patients showed
      positive CHO-hTSH-R cell stimulation, 11 patients showed positive porcine thyroid
      cell stimulation and 15 patients showed positive TBII. All the untreated patients
      showed positive results in at least one assay. Although significantly positive
      correlations were observed among CHO-hTSH-R cell stimulation, porcine thyroid
      cell stimulation and TBII activities, the IgG of several patients showed
      significant discrepancy in the assay results. In a patient with interferon
      induced hyperthyroidism only CHO-hTSH-R cell stimulation was positive, while
      porcine thyroid cell stimulation and TBII were negative. After the treatment with
      propylthiouracil for 6 months, CHO-hTSH-R cell stimulation became negative. The
      IgG of patients with Hashimoto's thyroiditis did not show significant stimulation
      of CHO-hTSH-R cells. These results suggest that the CHO-hTSH-R cell stimulation
      assay is clinically useful for the diagnosis and follow-up of patients with
      Graves' disease.

PMID- 7627343
TI  - Ectopic posterior pituitary tissue and paracentric inversion of the short arm of
      chromosome 1 in twins.
AB  - Twin boys with hypopituitarism, hypoplasia of the anterior pituitary gland.
      ectopic posterior pituitary tissue and paracentric inversion of the short arm of
      chromosome 1 are described. The smooth appearance at the base of the median
      eminence and the absence of a pituitary stalk at autopsy in these boys implies
      that the hypopituitarism resulted from a developmental aberration. It remains to
      be determined if there is a casual relationship between the chromosome 1 anomaly
      and hypopituitarism.

PMID- 7627344
TI  - Hypertension in disguise--a trap for the unwary.
AB  - A 36-year-old asymptomatic Chinese male with polycystic kidney disease (PKD)
      developed hypertension 1 year after the diagnosis of PKD. The patient was treated
      initially as for hypertension associated with PKD. However, over a 6-year period
      his hypertension became progressively difficult to control and he developed
      severe symptomatic hypokalemia. Subsequent investigations confirmed the presence
      of primary hyperaldosteronism. The initial computed tomographic scans of the
      adrenals did not reveal any definite adenomas. The patient subsequently underwent
      bilateral adrenal venous sampling, which suggested a left-sided source of
      aldosterone excess. A repeat computed tomography of the adrenals with fine cuts
      revealed a 6-mm diameter adenoma of the left adrenal gland. He underwent an
      uncomplicated left adrenalectomy. All antihypertensive and potassium supplements
      were stopped on the 5th postoperative day. Two and half years after the
      adrenalectomy he remains normotensive and normokalaemic without any medication.
      The case illustrates the importance of measuring serum potassium before
      initiation of any therapy and the need to consider secondary causes even if a
      primary association is known. It also reinforces the fact that when hypertension
      becomes difficult to control, a secondary cause has to be searched actively. The
      association between primary aldosteronism and renal cysts has been highlighted
      only recently. The association of polycystic kidneys and primary aldosteronism
      has been reported in the literature only once previously.

PMID- 7627346
TI  - ANA debates Medicare-Medicaid restructuring and education issues.

PMID- 7627347
TI  - Acute care NP: hired by nursing? Or medicine?

PMID- 7627348
TI  - Colors of the spectrum. Advanced practitioners in gerontology.

PMID- 7627345
TI  - Effects of selenium deficiency on thyroid necrosis, fibrosis and proliferation: a
      possible role in myxoedematous cretinism.
AB  - It has been suggested that selenium deficiency is a co-factor to iodine
      deficiency in the pathogenesis of myxoedematous cretinism. The mechanism proposed
      is that the generation of hydrogen peroxide is greatly increased in iodine
      deficient thyroid glands, and that selenium is involved in the control of
      hydrogen peroxide and its derived free radicals. This study was carried out to
      investigate the effect of the possibly impaired cellular defence mechanism
      associated with selenium deficiency on thyroid necrosis and tissue repair. For
      this purpose, we studied thyroid tissue from selenium- (SE-) and/or iodine
      deficient (I-) rats before and after an acute toxic iodine overload. In I-
      thyroids, necrotic cells were numerous. Acute iodine administration increased
      this effect. Necrosis was associated with transient infiltration of inflammatory
      cells. In I-SE+ thyroids the tissue resumed its normal appearance. In I-SE-
      thyroid glands, the iodide toxicity was stronger, with greater necrosis and
      inflammatory reaction. The inflammation resolved but was replaced by fibrotic
      tissue. Fifteen days after the toxic overload, the connective tissue volume was
      twice the control value. Before iodide overload, the proportion of dividing cells
      was equal in I-SE+ and I-SE- thyroids. Three days after the iodide overload, this
      proportion was increased in I-SE+ thyroids but reduced in the I-SE- thyroids.
      Overall, the I-SE- thyroids had four times fewer dividing cells than the I-SE+
      thyroids. In summary, selenium deficiency coupled to iodine deficiency increased
      necrosis, induced fibrosis and impeded compensatory epithelial cell
      proliferation. These results are compatible with histological and functional
      description of thyroid tissue from myxoedematous cretins.

PMID- 7627349
TI  - The nurse with no last name.

PMID- 7627350
TI  - Management perspectives. I am the nurse manager in a midsize hospital.

PMID- 7627351
TI  - The expanding vista of advanced practice nursing.

PMID- 7627352
TI  - Medicare and Medicaid reimbursement for NPs and CNSs.

PMID- 7627353
TI  - [Training and quality assurance: a future approach for blood transfusion].

PMID- 7627354
TI  - Lack of evidence for a role of HLA-DP in unexplained recurrent spontaneous
      abortion.
AB  - Using the "Polymerase Chain Reaction-Sequence Specific Oligoprobes" (PCR-SSOp)
      technique, we studied the HLA-DPB locus in both partners of 59 couples with a
      history of three spontaneous abortions, and of 38 control couples in order to
      determine the role of this centromeric region of the major histocompatibility
      complex (MHC) in the immune reaction needed for a favorable course of pregnancy.
      As no particular phenotypes were noted, and also neither excessive HLA-DP
      homozygosity in sterile women nor excessive HLA-DP allele sharing between sterile
      partners, this MHC class II sub-region would seem to play no role either directly
      or by linkage disequilibrium, in the development of normal pregnancy.

PMID- 7627355
TI  - [Fresh frozen plasma: a pilot study of the context of utilization and the
      indications].
AB  - The aim of this pilot study was to assess the feasibility of a tolerance study of
      qualified (secured by quarantine or solvent-detergent-treated) fresh frozen
      plasma (FFP) in real conditions of use. We included all patients receiving
      qualified FFP during a one-month observation period in three french hospitals
      (Besancon, Brest, Lyon). The 192 FFP transfusion episodes corresponded to 111
      patients. Only two thirds of all prescriptions corresponded to indications
      mentioned in the ministerial order of december 1991. Forty-two episodes consisted
      of FFP only; in the 150 remaining episodes, at least one product (mostly labile
      blood products) had been injected within 24 hours before or after the plasma
      injection. The free interval between FFP transfusion and the nearest associated
      product was usually less than three hours. Only one side effect was notified.
      This pilot study points out the difficulties of a tolerance study of qualified
      FFP in real conditions of use. It also raises the necessity to clarify current
      indications of FFP.

PMID- 7627356
TI  - [Viral safety of intravenous immunoglobulins G for therapeutic use].
AB  - Even though IV IgG concentrates are considered to be among the safest products
      derived from human plasma, some preparations have been associated with the
      sporadic transmission of NANB hepatitis and, specifically of hepatitis C. The
      risk of transmission may have decreased markedly for several IgG preparations
      since the availability of an immunological test to detect the antibodies against
      HCV in the starting plasma, but it has not been fully eradicated. Thus, in
      addition to established viral inactivation treatments, such as acid pH
      incubation, new methods have been (or are being) implemented to further reduce
      the risk of HCV infection through IV IgG concentrates. Among these methods are
      the solvent-detergent treatment already shown to be highly effective for the
      inactivation of HCV and other enveloped viruses in clotting factor concentrates,
      and nanofiltration for the specific removal of viruses on the basis of their
      size. Also, chromatographic methods have helped to improve the overall safety of
      the product not only by removing viruses but also by improving purity and thus
      favoring a better in vivo tolerance. This paper reviews the reported cases of HCV
      transmission and the viral validation data for various IV IgG processing steps
      and current specific viral inactivation methods. An overview of the present
      safety status of IV IgG concentrates is presented as well as the recent
      introduction of new promising techniques for the overall improvement of the
      safety of this plasma derivative.

PMID- 7627358
TI  - [Irregular antibodies. A comparative study of 2 series of 20,000 subjects: one
      with a conventional identification test, the other with gel-test].
AB  - The results of irregular antibody screening in two successive series of 21485 and
      19819 individuals were retrospectively analysed. All the irregular antibody
      screenings were performed with an autoanalyser according to Rosenfield and
      Lalezary [1, 2] but red cell antibody identification tests were not the same:
      conventional manual tests in the first series and gel-test Diamed in the second
      one. In spite of a bigger number of identification tests performed in the second
      series, the percentage of patients with irregular antibodies was approximately
      the same (2.27% and 2.22%) in each series. Analysis of identified specificities
      shows in the second series the increase of immune antibodies (+ 42.3%) especially
      antibodies with anti-Rh specificity and the decline of natural antibodies (-
      28.9%) essentially of anti-Lewis b and P1 antibodies. The sensitivity of both the
      gel-test and the autoanalyser screening for identification of immune antibodies
      are more or less the same. The sensitivity of gel-test probably gives a safer
      transfusion but increases the workload of both the laboratory and the blood bank
      delivery service.

PMID- 7627359
TI  - Response to special section: ethical decision making and persons with mental
      retardation (CQ vol. 3, no. 2).

PMID- 7627357
TI  - [Platelet collection by apheresis with reduced use of citrate: quantitative and
      qualitative evaluation of three protocols].
AB  - Three protocols of platelet collection by apheresis on Cobe Spectra with
      different citrate concentrations were compared. First we determined until what
      level we could diminish the ratio anticoagulant/whole blood flow to enhance the
      efficiency without clotting in the cell separator by platelet aggregates. We
      found that protocol 2 had a better platelet collection efficiency than the
      standard protocol 1: respectively 59% versus 52%. Protocol 3 had even a better
      efficiency but, due to the risk of clotting (5% of the procedures) we rejected it
      for routine use. We compared in vitro platelet functions of protocols 1 and 2 by
      aggregometry in vitro. The results with the different aggregating agents
      indicated that the less citrated environment kept the platelets more functional
      in vitro. A disadvantage of protocol 2 compared to the standard protocol is the
      more important number of platelet concentrates that contain more than 10(6)
      leucocytes.

PMID- 7627360
TI  - Do not resuscitate orders in the operating room: the birth of a policy.

PMID- 7627361
TI  - Euthanasia and assisted suicide in The Netherlands.

PMID- 7627362
TI  - Beyond autonomy to the person coping with illness.

PMID- 7627363
TI  - Judging medical futility: an ethical analysis of medical power and
      responsibility.

PMID- 7627364
TI  - Conflict in the pediatric setting: clinical judgment vs. parental autonomy.

PMID- 7627365
TI  - Reworking autonomy: toward a feminist perspective.

PMID- 7627366
TI  - Care ethics: a concept in search of a framework.

PMID- 7627367
TI  - Moving from autonomy to responsibility in HIV-related healthcare.

PMID- 7627368
TI  - Rights, duties, and limits of autonomy.

PMID- 7627369
TI  - Autonomous decision making and Japanese tradition.

PMID- 7627371
TI  - CQ sources. Beyond autonomy.

PMID- 7627372
TI  - Ethics committees: group process concerns and the need for research.

PMID- 7627370
TI  - The individual and healthcare in the new Russia.

PMID- 7627373
TI  - The good death, virtue, and physician-assisted death: an examination of the
      hospice way of death.

PMID- 7627374
TI  - Response to "Institutional morality, authority, and ethics committees: how far
      should respect for institutional morality go?" by Erich Loewy (CQ vol. 3, no. 4)

PMID- 7627375
TI  - Vestibular bibliography.

PMID- 7627376
TI  - The vestibulocollic reflex.
AB  - Stabilization of the head is required not only for adequate motor performance,
      such as maintaining balance while standing or walking, but also for the adequate
      reception of sensory inputs such as visual and auditory information. The
      vestibular organs, which consist of three approximately orthogonal semicircular
      canals (anterior, horizontal, posterior) and two otolith organs (utriculus,
      sacculus), provide the most important input for the detection of head movement.
      Activation of afferents from these receptors evokes the vestibulocollic reflex
      (VCR), which stabilizes head position in space. In this review, which is the
      outgrowth of a session of the vestibular symposium held in Hawaii in April, 1994,
      we discuss the neural substrate of this reflex and some aspects of the central
      processing involved in its production. Some topics are not considered, in
      particular the important interaction between the VCR and the cervicocollic reflex
      evoked by activation of neck afferents (70,119), and attempts to model the reflex
      (69).

PMID- 7627377
TI  - Investigation of the horizontal, vertical, and oblique optokinetic nystagmus and
      afternystagmus in squirrel monkeys.
AB  - A moving random dot pattern was projected onto a tangent screen in front of awake
      untrained monkeys that were always placed in upright position. Eye movements were
      recorded in two dimensions to study the oblique optokinetic nystagmus (OKN) and
      compare it to the horizontal and vertical OKN. Any direction of pattern movement
      across the screen could be achieved. The angular velocity of pattern movement was
      varied between 6 and 180 degrees/s. To display off-horizontal and off-vertical
      eye movements, the instantaneous direction and velocity of the eye movements were
      computed from the horizontal and vertical search coil voltages. At pattern
      velocities below 90 degrees/s, stimulus-direction and direction of the OKN slow
      phase matched very precisely. Above 90 degrees/s the slow-phase eye movement
      direction was systematically shifted toward the horizontal except for pure
      vertical stimulation. The slow-phase eye velocity at off-horizontal stimulation
      was inconstant, however; stable periods occurred repeatedly that were used to
      define the gain of OKN. Up to stimulus speeds of about 90 degrees/s the OKN gain
      did not depend on the direction of stimulation and of OKN. At higher velocities
      the gain decreased with the increasing angle between stimulus direction and
      horizontal. Practically no vertical optokinetic afternystagmus (OKAN) could be
      observed, in either the up or down direction. At the onset of afternystagmus
      after oblique stimulation the direction of the OKAN slow phase immediately
      shifted over to the horizontal. The data indicate that the slow-phase direction
      and gain of oblique OKN with the monkey's head upright can be described by the
      sum of a horizontal and a vertical velocity vector obtained during stimulation in
      these cardinal directions.

PMID- 7627378
TI  - Pharmacological activity of the Ginkgo biloba extract (EGb 761) on equilibrium
      function recovery in the unilateral vestibular neurectomized cat.
AB  - Locomotor balance recovery after unilateral vestibular neurectomy has been found
      strongly accelerated in the cat when the animals received a postoperative
      treatment with Ginkgo biloba Extract (EGb 761:50 mg/kg/d, i.p.), a result due to
      the improvement of plasticity mechanisms involved in vestibular compensation. The
      aim of this study was to determine which of the two main biochemical components
      (terpenes vs. flavonoids) contained in the extract was the most active in the
      recovery process, to test the influence of the route of administration, and to
      look for dose-dependent effects. Experiments were performed in six experimental
      groups of cats that were compared with each other and with three control groups.
      Comparisons were done on the recovery profile and time course of equilibrium
      function restoration, as quantified by the rotating beam test. Four experimental
      groups were treated with the standardized extract EGb 761 given orally (p.o.:2
      groups; 40 mg and 80 mg/kg) or intraperitoneally (i.p.: 2 groups; 50 mg and 25
      mg/kg), whereas the two others received only a special extract that did not
      contain the terpenes (i.p. administration: 25 mg and 10 mg/kg). Treatment was
      always given until complete recovery of locomotor balance function. The control
      groups received either no treatment (untreated cats), an oral vehicle (placebo
      cats), or a sham i.p. injection (sham cats). Results showed that locomotor
      balance recovery was significantly improved in all the experimental groups as
      compared to the control groups of cats, which recovered similarly and more
      slowly. Efficacy of the special extract without the terpenes was comparable to
      that of the total extract, indicating that the nonterpenic fraction was the most
      active biochemical constituent in this experimental model of central nervous
      system (CNS) plasticity. Pharmacological activity of the extract was also
      significantly better when given i.p. as compared to the p.o. route of
      administration, and dose-dependent effects were evidenced with the i.p.
      administration of the special extract without the terpenes, with a lower efficacy
      for the lowest dose (10 mg/kg). These data confirm that EGb 761 treatment serves
      as useful therapy in supporting brain functional recovery in this animal model of
      vestibular compensation and lead to a more precise understanding of the
      biochemical component that is active in this recovery process.

PMID- 7627379
TI  - Effects of full-field visual input on the three-dimensional properties of the
      human vestibuloocular reflex.
AB  - The three-dimensional (3-D) properties if the vestibuloocular reflex (VOR) were
      studied in six normal human subjects during passive whole-body rotations in
      darkness and with full-field visual input in light. Subjects were asked to fixate
      a point target stationary in space straight ahead or to imagine such a target in
      darkness. Using a 3-D rotating chair, subjects were rotated sinusoidally
      (frequency .3 Hz, maximum speed 37.5 degrees/s) about an earth-vertical axis for
      horizontal stimulation and about an earth-horizontal axis for vertical and
      torsional stimulation. The subject faced forward for vertical stimulation, 90
      degrees to the side for torsional stimulation, or 15 degrees to the right or left
      side for combined vertical and torsional stimulation. Left eye position was
      measured using 3-D search coils. The VOR response was quantified using the 3-D
      analogue of gain, a 3 x 3 matrix where each element describes the dependence of
      one component--torsional, vertical, or horizontal--of eye velocity on one
      component of head velocity. Average gain matrices were calculated for three
      cycles of rotation (10 s). Major findings were: (1) Gain values for the VOR were
      higher in light than in darkness for all directions. In light, vertical and
      horizontal responses were fully compensatory in both magnitude and direction,
      whereas the torsional responses were still weak. (2) Intersubject variability,
      large in the dark, was very small in the light for the vertical and horizontal
      responses but still considerable for the torsional.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7627380
TI  - Body orientation and regulation of the center of gravity during movement under
      water.
AB  - Professional divers were instructed to adopt a vertical posture under water with
      their feet fixed to the ground and to perform a fast forward or backward upper
      trunk bending movement in response to a tone. Kinematic and EMG analyses were
      performed. It was first noted that the divers adopted a forward inclined, erect
      posture, suggesting that the verticality was misevaluated, although the effects
      of gravity were still exerted on the otoliths. Second, the upper trunk movements
      were still accompanied by opposite movements of lower segments and, as a result,
      the center of gravity displacement was still minimized, although not so
      accurately as on the ground. The EMG pattern consisting of early activation of a
      set of trunk, thigh, and shank muscles continued to occur under water. These
      results suggest that "axial synergies" associated with upper trunk movements are
      learned motor habits that regulate the center of gravity position regardless of
      the equilibrium constraints.

PMID- 7627381
TI  - Horizontal rotation responses of medullary reticular neurons in the decerebrate
      cat.
AB  - This study examines the response of neurons in the medullary reticular formation
      of the decerebrate cat to sinusoidal yaw rotations in the plane of the horizontal
      semicircular canals. Responsive neurons that could be antidromically activated
      from the spinal cord appeared to be less sensitive to the rotary stimulus than
      the rest of the population or responsive neurons. Most neurons had response
      dynamics similar to those of semicircular canal afferents.

PMID- 7627382
TI  - The safety and versatility of video-thoracoscopy: a prospective analysis of 895
      consecutive cases.
AB  - BACKGROUND: The application of video-endoscopy to general thoracic surgery is
      radically changing the approach to many benign and malignant diseases of the
      chest. Since July 1991, we have performed 794 purely thoracoscopic and 101 video
      assisted thoracic surgical (VATS) procedures on 860 patients. STUDY DESIGN:
      Comprehensive, prospectively acquired data examining the specific indications for
      and outcomes of this new technique were prospectively entered into a thoracic
      surgical database. Preoperative, intraoperative, postoperative, and outcome
      variables were studied for the entire group as well as three high-risk cohorts:
      age over 70 years (n = 198), forced expiratory volume in one second (FEV1) of
      less than 1 L (n = 46), and Karnofsky performance index of less than 8 (n = 61).
      RESULTS: The 895 cases involved 449 men and 446 women of ages 15 to 89 years
      (mean 56 +/- 16 years standard deviation). The indications for surgery were
      diagnostic in 501 cases (56 percent), therapeutic in 244 cases (27 percent), and
      both diagnostic and therapeutic in an additional 150 cases (17 percent). The
      specific procedures performed were operations on the lung (569 cases), pleura
      (196 cases), esophagus (42 cases), mediastinum (51 cases), and pericardium (37
      cases). Fifty-seven percent of the procedures were for a malignant process and 43
      percent were for benign or infectious pathology. There were nine deaths for a
      series operative mortality rate of 1.0 percent. Thirteen patients (1.4 percent)
      required conversion to a limited thoracotomy for technical reasons. There were
      127 complications in 121 patients yielding a morbidity rate in all patients of 14
      percent. Mortality rates in the elderly, poor lung function, and depressed
      performance index cohorts were 1.5, 2.1, and 9.8 percent, respectively. Morbidity
      rates in these high-risk populations were 19, 30, and 18 percent, respectively.
      The median postoperative length of stay was three days after closed thoracoscopy
      and five days after VATS resection. CONCLUSIONS: These data underscore the
      flexibility, safety, efficacy, and potential for cost savings of videoscopic
      surgery in patients with thoracic diseases. The ability to perform excisional
      biopsy improves diagnostic specificity and sensitivity to nearly 100 percent.
      Video-assisted thoracic surgical techniques also offer a minimally invasive
      procedure with acceptable risk to patients heretofore inoperable by standard
      thoracotomy.

PMID- 7627383
TI  - Preliminary report of a prospective randomized study of octreotide in the
      treatment of severe acute pancreatitis.
AB  - BACKGROUND: Experimental and clinical studies on the effect of octreotide in the
      treatment of patients with acute pancreatitis have presented controversial
      results. Since January 1992, we have been conducting a prospective randomized
      study on the clinical effect of octreotide in severe acute pancreatitis, at three
      hospitals in Israel. STUDY DESIGN: The entering criteria included three or more
      of the Ranson's prognostic signs and computed tomographic findings of severe
      pancreatitis. Patients were randomly assigned to conservative treatment either
      with or without octreotide (0.1 mg injected subcutaneously three times a day).
      The end points of the study included: complication rate (adult respiratory
      distress syndrome [ARDS], sepsis, renal failure, pseudocyst, fistula, and
      abscess), length of hospital stay, and mortality. RESULTS: During the first two
      years (from January 1992 to December 1993), 51 patients entered the study. After
      evaluation, 13 patients were excluded due to failure to meet the entering
      criteria, incomplete data, or incorrect diagnosis. Of the remaining 38 patients,
      19 were assigned to octreotide (treatment group) and 19 to conservative treatment
      alone (control group). The two groups were matched with regard to age, sex,
      etiology, and severity of disease. The complication rate was lower in the
      treatment group compared with the control group with regard to sepsis (26
      compared with 74 percent, p = 0.004) and ARDS (37 compared with 63 percent, p =
      0.1). The hospital stay was shorter in the treatment group compared with the
      control group (17.9 compared with 34.1 days, p = 0.02). Death occurred in two
      patients in the treatment group and six patients in the control group.
      CONCLUSIONS: Although some of the parameters did not reach statistical
      significance, these preliminary results suggest that octreotide may have a
      beneficial effect in the treatment of patients with severe acute pancreatitis.
      This study is scheduled to continue for two more years.

PMID- 7627384
TI  - Spontaneous perforation of choledochal cyst.
AB  - BACKGROUND: Spontaneous perforation of the common bile duct in children is very
      rare and its etiology is unknown. We describe herein five patients treated for
      the spontaneous perforation of choledochal cyst and suggest the important factors
      leading to perforation. STUDY DESIGN: All patients were initially treated with T
      tube drainage through the perforated site. Cholangiography through the T tube was
      performed intraoperatively and the important factors leading to perforation were
      examined. Furthermore, histological examination of the perforated wall of the
      common bile duct was performed. RESULTS: Cholangiography through a T tube
      revealed the presence of a pancreaticobiliary junction malformation and filling
      defects (protein plugs) in the common channel in all patients. Postoperatively,
      the T tube was gently irrigated with a physiological salt solution until the free
      flow of bile into the duodenum was established. Histological examination showed
      that the wall near the perforation was covered with a granulation tissue that was
      present only at the limited area. CONCLUSIONS: Perforation of the common bile
      duct was related to the abrupt increase in intraluminal pressure due to
      obstruction by protein plugs at the common channel.

PMID- 7627385
TI  - Role of xanthine oxidase and leukocytes in postburn cardiac dysfunction.
AB  - BACKGROUND: Recent studies suggest that the cardiac dysfunction that occurs after
      a major burn is mediated by oxygen-derived free radicals. This hypothesis is
      based on the fact that superoxide dismutase and catalase, given with fluid
      resuscitation from burn injury, provided significant cardioprotection. STUDY
      DESIGN: In this present study, rats received either enteral allopurinol or
      tungsten-enriched diets to determine if xanthine oxidase mediates postburn
      defects in cardiac contraction and relaxation. Polymorphonuclear neutrophil (PMN)
      were depleted to examine the contribution of PMN-derived factors to postburn
      cardiac dysfunction. Rats were divided into eight groups: groups 1 to 6 received
      regular chow, and groups 7 and 8 received tungsten-enriched diets for 14 days
      before study. Groups 2, 4, 6, and 8 were given a third-degree burn comprising 43
      +/- 2 percent total body surface area and were resuscitated with Ringer's
      lactated solution for 24 hours (4 mL/kg/percent burn). In group 2, burned rats
      received fluid resuscitation alone; in group 4 (n = 10), rats were given
      allopurinol, 10 mg/kg daily by gastric lavage for five days preburn, group 6 (n =
      11) received vinblastine (0.75 mg/kg) four days preburn, and group 8 (n = 11)
      received tungsten-enriched diets for 14 days before burn; sham burn controls
      included vehicle-treated (n = 10), allopurinol-treated (n = 8), PMN-depleted (n =
      8), and tungsten-fed rats (n = 11) (groups 1, 3, 5, and 7, respectively).
      RESULTS: Burn injury produced mild hypotension, hypothermia, bradycardia, and a
      significant decrease in left ventricular performance, despite aggressive fluid
      resuscitation (group 2). Allopurinol, tungsten-enriched diets, and PMN depletion
      partially attenuated burn-induced cardiac contractile dysfunction and improved
      left ventricular responsiveness to increases in preload, coronary flow rate and
      exogenous calcium. CONCLUSIONS: Our data suggest that xanthine oxidase-derived
      oxygen metabolites and PMN-derived mediators contribute to postburn cardiac
      contractile deficits.

PMID- 7627386
TI  - Ranitidine reduces postoperative interleukin-6 induced C-reactive protein
      synthesis.
AB  - BACKGROUND: The mechanism of post-traumatic immunosuppression is still not known
      in detail. However, histamine released during trauma and major surgery may play a
      significant role in the process. Previously, we showed that the histamine-2
      receptor antagonist (H2RA), ranitidine, reduced trauma-induced suppression of
      certain immunological parameters. STUDY DESIGN: The effect of perioperative
      ranitidine on postoperative change in plasma interleukin-6 (IL-6) and serum C
      reactive protein (CRP) levels was assessed in 23 women undergoing elective
      abdominal hysterectomy. The patients were randomized to receive intravenous
      ranitidine, 100 mg twice a day from skin incision, for two days, followed by oral
      ranitidine, 150 mg twice a day, for a further three days, or no ranitidine.
      Interleukin-6 and CRP were analyzed in plasma and serum, respectively, drawn
      preoperatively and six, 24, 48, and 120 hours after skin incision. RESULTS:
      Routine blood analyses, clinical data (except age), duration of surgery,
      anesthesia, antibiotic prophylaxis, blood loss, and perioperative blood
      transfusion were similar in the two groups. Interleukin-6 levels were
      significantly increased in all patients and without difference between the
      ranitidine-treated and non-ranitidine-treated patients after six, 24, and 48
      hours compared to preoperative levels, respectively. C-reactive protein levels
      were also significantly increased in all patients after 24, 48, and 120 hours,
      respectively; however, at 48 hours, CRP was significantly reduced in ranitidine
      treated patients compared with non-ranitidine-treated patients (p = 0.02).
      CONCLUSIONS: These results suggest that histamine-2 receptor activation
      mechanisms may not be involved in postoperative IL-6 synthesis. However, the
      reduced CRP level in ranitidine-treated patients suggests that H2RAs modulate IL
      6 signal transduction in hepatic cells.

PMID- 7627388
TI  - Duplex-guided compression of iatrogenic femoral pseudoaneurysms.
AB  - BACKGROUND: Iatrogenic pseudoaneurysms are a major complication following
      percutaneous cannulations of the femoral artery. Surgical repair has been the
      traditional treatment modality. Recent reports have introduced duplex-guided
      compression as a means of nonoperative management of these injuries. We proposed
      to determine if duplex-guided compression of femoral pseudoaneurysms could be
      successfully performed, could be done without complication, and could maintain
      thrombosis on long-term follow-up. STUDY DESIGN: All patients presenting with
      large groin hematomas following invasive percutaneous femoral artery procedures
      over a seven-month period were studied using color-flow duplex analysis. Six
      pseudoaneurysms were discovered and successfully treated with duplex-guided
      compression. All patients were then followed-up prospectively with both early and
      long-term repeat duplex analysis. RESULTS: All patients were rescanned 72 hours
      later and the pseudoaneurysms remained thrombosed. Upon returning for long-term
      follow-up examination, patients again had duplex confirmation of thrombosis, with
      a mean follow-up time of 21 months (range, five to 29 months). No complications
      attributable to this technique have been noted. CONCLUSIONS: This study confirms
      the clinical usefulness of duplex-guided compression in the evaluation and
      treatment of iatrogenic femoral pseudoaneurysms.

PMID- 7627387
TI  - Insulin-like growth factor-II expression in carcinoma in colon cell lines:
      implications for autocrine actions.
AB  - BACKGROUND: In the gastrointestinal tract, insulin-like growth factor-II (IGF-II)
      messenger RNA (mRNA) is localized mainly in mesenchymal cells, and is more
      abundant in the fetus than in the adult. The purposes of this study are to
      characterize the gene expression of IGF-II at the mRNA and protein level in seven
      different epithelial cell lines derived from colon carcinomas and to determine
      the action of IGF-II and IGF-receptors on a colon carcinoma cell line. STUDY
      DESIGN: Insulin-like growth factor-II mRNAs were examined by Northern analysis;
      conditioned media from colon carcinoma cells were concentrated, chromatographed,
      and examined by a specific IGF-II radioreceptor assay. Insulin-like growth factor
      receptors were examined by radioligand binding assays. The mitogenic role of IGF
      II was determined by a 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium
      bromide assay. RESULTS: Multiple sizes of IGF-II mRNAs were expressed in all
      colon carcinoma cell lines tested (six human cell lines: HCT116, COLO 205, COLO
      320 DM, LoVo, DLD-1, and HT29, and one mouse cell line: MC-26). In the
      conditioned media of COLO 205 and HCT116 cells, 7.5 kilodaltons IGF-II and high
      molecular form (IGF-II and IGF binding protein complex) were detected. Both Type
      I and Type II IGF receptors were present on COLO 205 cells whose growth was
      stimulated by IGF-II. Addition of anti-IGF-I receptor and anti-IGF-II antibody in
      the cell culture significantly depressed growth of the COLO 205 cell line in the
      presence or absence of exogenous IGF-II. CONCLUSIONS: Insulin-like growth factor
      II mRNAs are expressed in human and mouse colon carcinoma cell lines, which may
      induce production of a significant amount of biologically active IGF-II protein.
      The IGF-II secreted by COLO 205 cells may stimulate cell growth in an autocrine
      fashion through the Type I IGF receptors.

PMID- 7627389
TI  - Reversal of small intestinal bypass operations and concomitant vertical banded
      gastroplasty: long-term outcome.
AB  - BACKGROUND: Long-term complications of jejunoileal bypass (JIB) have been
      reported, prompting restoration of intestinal continuity and concomitant
      performance of vertical banded gastroplasty (VBG) for weight control. The aim of
      this study was to evaluate the presentation and reversal of JIB complications,
      late complications, mortality, and long-term weight control in patients who have
      undergone JIB reversal and concomitant VBG. STUDY DESIGN: From 1981 to 1994, 37
      patients were treated for complications from JIB that included diarrhea (73
      percent), arthritis (46 percent), malnutrition (22 percent), urolithiasis (19
      percent), electrolyte disorders (19 percent), and lack of weight loss (8
      percent). Four patients required preoperative parenteral nutrition to correct
      protein and electrolyte imbalances. Surgical management of all 37 patients
      included restoration of bowel continuity and VBG during the same operative
      procedure. RESULTS: Postoperative complications occurred in 11 patients,
      including prolonged ileus in seven patients, pancreatitis in three patients, and
      infectious complications in two. There were no deaths. Late morbidity included
      staple line dehiscence in four patients, incisional hernia in three patients, and
      reversal of the VBG in one. All patients with diarrhea, malnutrition, electrolyte
      disorders, and lack of weight loss had resolution of their symptoms, while
      urolithiasis and arthritis resolved in 86 and 53 percent of patients,
      respectively. In patients available for five-year follow-up evaluation, weight
      changes were small, shifting from a preoperative weight of 87 +/- 19 to 90 +/- 19
      kg at five years (mean +/- SD). CONCLUSIONS: Restoration of intestinal continuity
      combined with VBG is a safe and effective operation that will reverse most of the
      long-term complications of JIB and provide stable weight control for up to five
      years.

PMID- 7627390
TI  - VATS: quo vadis?

PMID- 7627391
TI  - Groin laparoscopy: a new technique for contralateral groin evaluation in
      pediatric inguinal hernia repair.

PMID- 7627392
TI  - Use of the vermiform appendix as an internal urinary device in gynecologic
      oncology.

PMID- 7627393
TI  - A simple technique for the use of a variable length compilation vein graft in
      major venous injury.

PMID- 7627394
TI  - A simple, safe technique for stapled reconstruction after right hemicolectomy.

PMID- 7627395
TI  - Cancer staging using the American Joint Committee on Cancer TNM System.

PMID- 7627396
TI  - Gallbladder polyps are a common ultrasonographic finding.

PMID- 7627397
TI  - Pressure ulcer staging systems.

PMID- 7627398
TI  - Indices to include in wound assessment.

PMID- 7627399
TI  - Frequency of reassessment of pressure ulcers.

PMID- 7627400
TI  - Indices to include in wound healing assessment.

PMID- 7627401
TI  - Methods for assessing change in pressure ulcer status.

PMID- 7627402
TI  - Methods for assessing change in ulcer status.

PMID- 7627403
TI  - Methods for measuring size in pressure ulcers.

PMID- 7627404
TI  - Determination of bacterial burden in wounds.

PMID- 7627405
TI  - Measuring healing in wounds.

PMID- 7627406
TI  - Expected outcomes for the treatment of pressure ulcers.

PMID- 7627407
TI  - Pressure ulcers: definition and assessment parameters.

PMID- 7627408
TI  - OUtcomes in prospective studies and clinical trials.

PMID- 7627409
TI  - Outcomes in quality improvement activities.

PMID- 7627410
TI  - Outcomes in surgical intervention.

PMID- 7627411
TI  - Quality of life considerations.

PMID- 7627412
TI  - Definition of a pressure ulcer.

PMID- 7627413
TI  - Policy issues in pressure ulcer healing.

PMID- 7627414
TI  - Recent changes in federal regulations.

PMID- 7627415
TI  - Legislative initiatives impacting wound care.

PMID- 7627416
TI  - Description of NPUAP. National Pressure Ulcer Advisory Panel.

PMID- 7627417
TI  - Evaluation of moisture penetration through skin protectant barriers by paper
      chromatography.
AB  - Currently, there is no convenient and safe experimental method in the literature
      to evaluate skin protectant formulations for barrier properties. A novel and
      simple experimental method, based on paper chromatography, was developed to
      screen a broad spectrum of skin protectants available for moisture penetration.
      The method involves the use of paper chromatography for determining the Moisture
      Penetration Rate through a thin barrier film of a given skin protectant product.
      It is simple, inexpensive, convenient, and safe and was used to evaluate 12
      products currently used as skin protectants. This method can be used by
      formulators in their development efforts and by caregivers to determine the
      barrier properties of various products in a short period of time without
      expensive instrumentation or extensive time commitments. Skin irritation
      resulting from fecal and urinary incontinence is a common problem for geriatric
      patients (Fiers & Siebert, 1993, Talbot, 1994). Various products on the market
      today are used as protective barriers to prevent skin irritation from moisture
      penetration. However, from the caregiver's perspective, there is a need for
      identifying the best product or the relative ranking of products based on
      suitable test methods. There is a lack of suitable in vitro test methods to
      screen skin protectant barriers (Guillemin, Murset, Lob, & Riquez, 1974; Pigatto,
      Bigardi, Legori, Altomare, & Finzi, 1993) on the market. For any method to be
      acceptable it must be convenient, simple, reproducible, and safe for use on human
      volunteers. More importantly, it must have clinical relevance.

PMID- 7627418
TI  - Evaluation of ibuprofen for pressure ulcer prevention: application of a rat
      pressure ulcer model.
AB  - This blinded study describes the effect of ibuprofen (IBU) on experimental
      pressure ulcers (PU) induced in the fuzzy rat model. Ibuprofen's fibrinolytic
      activity has been found effective in preserving dermal vasculature in rats
      following burn injury. Experimental pressure ulcers were generated on the hips of
      fuzzy rats with the aid of computer control, using five daily, 6-hour pressure
      sessions. In the first study, 17 rats received intraperitoneal (I.P.) injection
      of IBU or saline control after each pressure session. In the second study, 44
      rats received IBU or control, before, during, and after application of pressure
      by I.P. or intramuscular (I.M.) injections. Quantitation of histology is based on
      five prominent lesions, including: ulceration, infarction, panniculus carnosus
      necrosis, fat atrophy, and deep muscle necrosis. The following hypothesis was
      tested: Reperfusion injury and vascular occlusion in pressure ulcers may be
      similar to that which occurs in burns and, therefore, is responsive to IBU
      intervention. The results indicate that IBU does not have significant effects on
      the development of pressure ulcers. The mechanisms of IBU action in other organ
      and tissue systems are discussed in relation to the effect of IBU on the pressure
      ulcer model.

PMID- 7627419
TI  - [Alternatives to conventional polysomnography in the diagnosis of the sleep apnea
      syndrome].

PMID- 7627420
TI  - [A morphometric model of hypersensitivity pneumonitis in the aging rat].
AB  - Our objective was to develop an experimental model of hypersensitivity
      pneumonitis in the aging rat. The following hypothesis was proposed:
      hypersensitivity pneumonitis in the aging rat will be evident in alterations in
      cells harvested by bronchoalveolar lavage (BAL) and in an increase in alveolar
      interstitial tissue. Sixty animals with a mean age of 18 months were divided into
      2 groups. Group 1 contained healthy, untreated animals and group 2 contained
      unhealthy animals that had been exposed to bovine seralbumin (BS). BAL and
      morphometric analysis of the lung was performed. The percentage of lymphocytes,
      polymorphonuclear, leukocytes and alveolar macrophages were determined in BAL.
      The morphometric variables studied were mean linear intersection (Lm), length of
      alveolar cord, wall thickness, tissue density and number of measurements of
      alveolar cord. The results show that the unhealthy animals had higher (p < 0.001)
      percentages of lymphocytes in BAL, lower Lm, diminished alveolar cord and thinner
      walls, as well as greater tissue density and a higher number of measurements. All
      differences were statistically significant (p < 0.001). These results lead to the
      conclusion that exposure of the aging rat to BS produces an increase in
      lymphocytes in BAL and an increase in interstitial alveolar content, findings
      that are related to alveolar-interstitial inflammation.

PMID- 7627421
TI  - [An evaluation of the bronchodilator response with beta agonists in patients with
      chronic obstructive pulmonary disease].
AB  - The aim of this study was to analyze the functional reversibility and establish
      the most appropriate index and minimum dose of beta-2-agonist in patients with
      chronic obstructive pulmonary disease (COPD). Sixty patients with COPD (FEV1/FVC
      < 70%) in stable phase. After taking baseline forced spirometry readings, we
      applied the accumulated dose-response technique, administering 0.2 mg salbutamol
      every 10 minutes up to a maximum dose of 1 mg. Spirometric readings were taken 10
      minutes after each dose. Response was evaluated with absolute values of FEV1 and
      with percent improvement over baseline FEV1 over the theoretical value and over
      the possible value. We calculated the correlation coefficient between baseline
      FEV1 and response, as measured by each of the aforementioned indices. No
      significant improvement was observed for doses higher than 0.4 mg salbutamol in
      either absolute values or percentage of baseline or theoretical values. Response
      was not significantly improved over 0.2 mg as measured by percent of possible
      response. Percent of theoretical value was the index that showed the least
      dependence on baseline FEV1 for each dose of salbutamol. A minimum dose of 0.4 mg
      salbutamol, or an equivalent dose of another similar sympathicomimetic drug,
      should be used for evaluation of bronchodilation response in patients with COPD.
      Response should be evaluated by percent of theoretical value.

PMID- 7627422
TI  - [Primary spontaneous pneumothorax. A retrospective study of 495 cases].
AB  - We conducted a retrospective study of patients treated in our department for
      primary spontaneous pneumothorax (PSP) between 1986 and 1993. The 495 patients
      were between 12 and 81 years old (mean 28.2 years). Four hundred fifteen (83.8%)
      were men and 80 (16.2%) were women. PSP was in the right lung in 262 cases
      (52.9%) and in the left lung in 215 (43.5%). Both sides were affected in 18 cases
      (3.6%). The initial treatment was pleural drainage; small caliber drains were
      used in 85 and no associated complications were observed. On 185 occasions
      (37.3%), patients required surgical repair as a result of air leaks, recurrence
      or acute hemorrhage. There were postsurgical complications in 15 cases (8.1%) but
      no recurrences or deaths after surgery. We observed no significant differences in
      the number of recurrences after use of conventional drains or small caliber
      drains. Nor were there differences in mean time of hospital stay or complications
      after conventional surgery or video assisted surgery, a technique that has only
      recently been introduced. We conclude that PSP responds well to treatment with
      pleural drains and that small caliber catheters offer a good alternative for
      treating first episodes. Surgery is indicated when there is recurrence or when
      air leaks are persistent. At present, video assisted thoracoscopic surgery has
      successfully replaced axillary thoracotomy for most patients.

PMID- 7627423
TI  - [Inflammation mediators (eosinophilic cationic protein, ECP) in a normal
      population and in patients with bronchial asthma or allergic rhinitis].
AB  - We analyzed serum levels of eosinophilic cationic protein (ECP), one of the 4
      main eosinophilic proteins; ECP is released from an activated cell and acts as a
      mediator of inflammation. Serum samples from 139 persons were studied
      prospectively. Fifty-three individuals from the general population provided the
      control group. Eighty-six consecutive patients were also studied: 69 with
      bronchial asthma and 17 with allergic rhinitis and no signs of asthma. The level
      of severity of disease was established in the asthmatics by the method proposed
      by Aas (Aas score), based on symptoms and medications received within the last
      year. We also classified these patients as having mild, moderate or severe asthma
      according to the latest criteria issued by the International Consensus for
      Diagnosis and Treatment of Asthma. Atopic status was estimated by skin Prick
      tests. ECP levels in the control group (9.34 +/- 5.76 micrograms/l) were
      significantly lower (p < 0.001) than those of the total population of patients
      (17.59 +/- 16.85 micrograms/l). The mean for patients with rhinitis was 14.76 +/-
      10.94 micrograms/l, whereas it was 18.29 +/- 18 micrograms/l in the asthmatics;
      the levels for both groups were statistically different from that of the control
      group (p < 0.03 and p < 0.001, respectively). Levels by degrees of severity
      established at the time of revision and by sensitivity to allergens were also
      significantly different from the level of the control group, although the mean
      levels were low in the group of severely affected patients who had received
      treatment with inhaled corticoids.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7627424
TI  - [Bochdalek's hernia in an adult with stomach volvulus and extrapulmonary
      sequestration].
AB  - We report a case of Bochdalek's hernia with volvulus of the stomach and
      extrapulmonary sequestration in an adult. A 27-year-old woman presented acute
      respiratory failure, pain in the left side of the chest and recurrent vomiting of
      sudden onset. Upon examination there was pain in the left hypochondrium that was
      not tolerated in decubitus position. A chest film showed an "arch" at the base on
      the left side and an upper gastrointestinal series revealed volvulus of the
      stomach. After a left thoracotomy, the stomach, spleen and greater omentum were
      found displaced into the thoracic cavity. After the viscera were confined to the
      abdomen, the hernia was repaired and the pulmonary sequestration was removed. Two
      years later, the patient was asymptomatic and a chest film was normal.

PMID- 7627425
TI  - [Acute pancreatitis and sarcoidosis: a case report and review of the literature].
AB  - We describe a case of sarcoidosis that began as acute pancreatitis. Diagnosis was
      established by mediastinoscopy. Although involvement of the pancreas is rare and
      in general asymptomatic, we conclude that sarcoidosis should be included in the
      long list of factors that can trigger acute pancreatitis.

PMID- 7627426
TI  - [Actinomyces as the etiology of empyema].
AB  - Thoracic actinomycosis represents 25% of all cases of the disease, whose
      presentation varies greatly. Pleural involvement is unusual and only rarely is it
      found as an isolated sign. We describe 2 cases of empyema due to actinomycosis;
      both cases responded well to surgical drainage and antibiotics.

PMID- 7627427
TI  - [Systemic cryptococcosis and pneumocystosis in an HIV-positive patient].
AB  - Cryptococcosis is one of the most common opportunistic infections in AIDS
      patients. Neurological symptoms are the most frequent clinical presentation of
      this fungal infection, and pulmonary involvement is clinically much less evident.
      We report the case of a patient who was treated in the emergency room for acute
      respiratory failure but who did not survive. Microbiologic and histopathologic
      studies demonstrated simultaneous pulmonary infections with Cryptococcus
      neoformans and Pneumocystis carinii. We discuss this clinical presentation of
      cryptococcosis with no neurological manifestations, and the importance of
      concurrent infections by several opportunistic organisms that may go
      unrecognized.

PMID- 7627428
TI  - [A report on the Spanish Registry of Patients with Alpha 1-Antitrypsin
      Deficiency. The Alpha 1-Antitrypsin Deficiency Study Group].

PMID- 7627429
TI  - [The surgery of bronchogenic carcinoma in Spain. A descriptive study. The
      Cooperative Group on Bronchogenic Carcinoma of SEPAR (GCCB-S). Sociedad Espanola
      de Neumologia y Cirugia Toracica].

PMID- 7627430
TI  - [Pleural effusion with a long-term evolution secondary to a liver transplant].

PMID- 7627431
TI  - The distribution of the magnetic field in the spine depends on the composition of
      bone marrow.
AB  - Although the composition of bone marrow with hemopoietic cells, fat cells, and
      extracellular fluid can be roughly assessed by standard MR-imaging techniques and
      especially water and lipid-selective chemical-shift-imaging methods, a new
      approach to the characterization of the magnetic properties of marrow was
      performed by special field-mapping techniques. The distribution of the magnetic
      field inside and outside vertebral bodies containing paramagnetic substances was
      systematically studied for phantoms and by measurements in vivo. Nineteen healthy
      volunteers and 26 patients with alterations of the bone marrow due to hematologic
      disease were examined. The amount of paramagnetic substances in the marrow was
      estimated by measuring steps of Larmor frequency of the water resonances at the
      transition between vertebral bodies and adjacent intervertebral disks. These
      frequency steps were exhibited by MAGSUS imaging on a 1.5 Tesla whole-body
      imager. Additional volume-localized 1H spectroscopy allowed a more quantitative
      assessment of the spectral components. The measured frequency steps of the water
      resonances ranged between 0 and 26 Hz for the healthy volunteers examined. In
      contrast, patients with pathologically altered marrow and high amount of
      paramagnetic substances revealed frequency steps of up to 85 Hz. The frequency
      steps in 8 patients after bone marrow transplantation (BMT) with slow
      reconstitution (mean 48.9 Hz, standard deviation (s.d.) 21.7 Hz) were
      significantly (p < 0.001) higher than in normal volunteers. Seven BMT patients
      with good reconstitution (frequency steps: mean 16.7 Hz, s.d. 13.9 Hz) were not
      clearly different from the healthy subjects. Six patients with acute leukemia
      showed significantly (p < 0.01) increasing frequency steps during initial
      cytotoxic treatment: The frequency steps increased from a mean of 4.7 Hz (s.d.
      2.7 Hz) before treatment to a mean of 30.2 Hz (s.d. 14.6 Hz) after a few months
      of therapy.

PMID- 7627432
TI  - Improved excitation pulse bandwidths using shaped pulses, with application to
      heteronuclear half filters in macromolecular NMR.
AB  - The advantageous use of sinc-shaped pulses in heteronuclear half filters is
      explored for studying biological macromolecules. The typical square, or hard,
      pulse used in half-filter pulse sequences for heteronuclear excitation results in
      suboptimal suppression of unwanted resonances due to incomplete inversion of
      spins. The novel use of short-duration shaped pulses applied at high power
      achieves more uniform excitation profiles over the extended frequency ranges
      often needed for heteronuclear filtering. This approach is used in the
      development of a double-tuned omega 1, omega 2-double-half-filtered, double
      quantum-filtered COSY experiment. The efficiency of this experiment incorporating
      sinc pulses compares favorably with that obtained with square pulses in a mixture
      of 13C-labeled and unlabeled amino acids. Sinc-pulse-filtered spectra of the 24
      kDa methionine repressor protein dimer MetJ, uniformly 13C-labeled expect at two
      unlabeled methionine residues, were also obtained to demonstrate the utility of
      this approach in biomacromolecular studies.

PMID- 7627433
TI  - The effect of inhomogeneous sample susceptibility on measured diffusion
      anisotropy using NMR imaging.
AB  - Water diffusion measurements in white matter of freshly excised pig spinal cord
      and in parenchyma of fresh celery (excluding the fibers along the edge of the
      stalk) were performed using NMR at 200 MHz. In white matter of pig spinal cord,
      the measured diffusion coefficient is anisotropic and independent of sample
      orientation with respect to the magnetic field. In celery parenchyma, diffusion
      is isotropic and independent of orientation in the magnetic field when using a
      diffusion sequence that gives results independent of self-induced magnetic-field
      gradients. However, when the standard diffusion pulse sequence that gives results
      dependent upon self-induced magnetic-field gradients is used, diffusion in celery
      appears isotropic when the stalk is oriented parallel to the magnetic field but
      anisotropic when oriented perpendicular. Susceptibility variations leading to
      anisotropic self-induced magnetic-field gradients approximately 3 kHz/cm in
      magnitude when the celery is oriented perpendicular to the magnetic field can
      explain this apparent anisotropic diffusion. A study of the apparent diffusion
      coefficient (ADC) in celery as a function of diffusion times ranging from 8 to 22
      ms indicates that the motion is at most only slightly restricted. Therefore,
      although the effect is not seen in all types of samples, one must be aware that
      self-induced gradients may affect the ADC and may cause isotropic diffusion to
      appear anisotropic. In addition, NMR experiments that change diffusion
      sensitizing gradient timings to study restricted diffusion change the effects of
      the self-induced gradients as well as the effect of barriers on the ADC,
      complicating interpretation.

PMID- 7627434
TI  - Phase-sensitive two-dimensional experiment on living animals.
AB  - This report describes the first 1H-1H phased spectrum obtained in vivo from the
      hind-leg muscles of an intact mouse. TOCSY correlations can follow the complete
      spin system and give a more detailed graph of each molecule than can COSY. TOCSY
      is also better suited than COSY for studying long fatty-acid chains. All the
      peaks are in phase in a TOCSY experiment and the intensities of the cross
      correlation peaks are less sensitive to low digitalization in the t1 domain than
      are those of COSY. The improvement in sensitivity was estimated by measuring the
      volumes of the cross-correlation peaks in COSY and TOCSY spectra.

PMID- 7627435
TI  - Development of an electronically tunable L-band resonator for EPR spectroscopy
      and imaging of biological samples.
AB  - While interest in the EPR spectroscopy and imaging of biological samples
      triggered the development of numerous resonator and microwave-bridge designs
      operating at high RF and L-band frequencies, a number of important technical
      problems remain. Two of these problems are the occurrence of sample-induced
      drifts in resonance frequency of the resonator and the intrinsic limitations in
      sensitivity of low-frequency EPR measurements. In an effort to address these
      problems, an approach was developed for obtaining fixed-frequency EPR
      measurements, utilizing a low-phase-noise fixed-frequency oscillator as a
      microwave source and an electronically tunable ceramic re-entrant L-band
      resonator, which was locked to the oscillator via automatic frequency control
      (AFC). The tunable microwave resonator described in this paper employs a voltage
      controlled piezoelectric actuator for adjustment of the resonance frequency via
      variations of the equivalent capacitance of the resonator. Design considerations
      and data, as well as schematic drawings and test results, are presented. The
      reported approach provides true fixed-frequency operation under a wide range of
      sample and environment conditions and over prolonged periods of time. The use of
      this tunable resonator design in conjunction with an ultra-low-noise fixed
      frequency oscillator should enable enhanced sensitivity in EPR measurements of
      large lossy biological samples.

PMID- 7627436
TI  - Improved sensitivity of HSQC spectra of exchanging protons at short interscan
      delays using a new fast HSQC (FHSQC) detection scheme that avoids water
      saturation.

PMID- 7627437
TI  - C-band ESEEM of strongly coupled peptide nitrogens in reduced two-iron
      ferredoxin.

PMID- 7627438
TI  - From denial to recognition: attitudes toward Holocaust survivors from World War
      II to the present.
AB  - This paper discusses the complex attitudes of Israeli society and mental health
      professionals toward the survivors of the Nazi Holocaust. While the nascent state
      of Israel provided refuge for the Holocaust survivors and offered them a new
      identity and opportunity to rebuild their lives, it also demanded that they
      abnegate their former identities, their Holocaust experiences above all, and
      repress all the emotional problems that the Holocaust created. In the nearly 5
      decades since the first survivors arrived on Israel's shores with their accounts
      of barely imaginable horror, society's attitudes toward the survivors have traced
      a tortured course, throughout which the views of the helping professions have
      mirrored, rather than led, those of the general public. This paper describes the
      process of change in attitudes and attempts to explain this process.

PMID- 7627439
TI  - Attitudes of therapists toward Holocaust survivors.
AB  - This study examined current feelings and attitudes toward Holocaust survivors in
      a sample of 205 Israeli mental health professionals. Subjects were asked to read
      two vignettes each describing an aged trauma victim who had recently applied for
      treatment. The first vignette presented a Holocaust survivor and the second a war
      veteran. The two "patients" were otherwise similar in background and clinical
      picture. After reading each vignette, subjects were asked to report their
      feelings toward the patient. Subjects also completed a detailed questionnaire
      that assessed attitudes on several issues related to the Holocaust. Feelings
      toward the Holocaust survivor were found to be more intense and more positive
      than feelings toward the combat veteran. Therapists' attitudes toward Holocaust
      survivors were also found to be highly and consistently positive. Compared to
      previous reports, they appear to reflect a change of heart in relation to the
      past. Therapist background variables were not found to play a major role in
      determining attitudes toward Holocaust survivors.

PMID- 7627440
TI  - Therapeutic response to combat stress reaction during Israel's wars:
      introduction.

PMID- 7627441
TI  - Diagnosis and treatment of combat stress reaction: current attitudes of military
      physicians.
AB  - This study examined the attitudes of 203 Israel Defense Forces (IDF) military
      physicians regarding the causes and treatment of combat stress reaction. The
      findings indicate that subjects tended primarily to endorse situational rather
      than predispositional explanations for the causation of the CSR. They attributed
      the highest levels of responsibility for treatment to the frontline physician and
      to commanders, and the least amount of responsibility to the casualty himself.
      These findings suggest that military physicians do not hold CSR casualties
      responsible for the causation or the treatment of the stress reaction. CSR is now
      viewed within the "medical model." It is considered by doctors to be within the
      purview of medicine and CSR casualties are considered legitimate objects of
      medical concern. The stigma attached to the phenomenon in the past thus appears
      to have diminished considerably.

PMID- 7627442
TI  - Mental health officers' causal explanations of combat stress reaction.
AB  - This study examined causal attributions for combat stress reaction (CSR) among
      117 Israel Defense Forces (IDF) mental health officers. The impact of case
      characteristics (the level of objective stress in the situation, reaction of
      others in the same situation, soldier's previous functioning, and type of
      symptomatology) and respondent characteristics (professional affiliation,
      therapeutic orientation) on these attributions was also examined. Results show
      that mental health officers view CSR primarily as a response to external
      circumstances; it is not generally seen as resulting from personality traits or
      intrapsychic processes. Findings also indicate that causal attributions were
      influenced at least to some degree by the clinicians' professional affiliation,
      their therapeutic orientation, and their knowledge of the casualty's prior
      functioning.

PMID- 7627443
TI  - Oscillating between denial and recognition of PTSD: why are lessons learned and
      forgotten?
AB  - Consistent observations suggest that denial of PTSD and blaming of its victims
      are not isolated omissions or distortions but a pattern that spans over time,
      crosses national and cultural boundaries, and defies accumulated knowledge. This
      article traces the origins of these attitudes and offers three explanations: (a)
      mental health professionals are unable to transcend prevailing cultural and
      social norms; (b) they are "blinded" by professional theories; and (c) denial may
      stem from a fundamental human difficulty in comprehending and acknowledging our
      own vulnerability.

PMID- 7627444
TI  - The therapeutic use of ritual and ceremony in the treatment of post-traumatic
      stress disorder.
AB  - The therapeutic purposes and effects of specially designed ceremonies in the
      treatment of persons with post-traumatic stress disorder are described.
      Ceremonies compartmentalize the review of the trauma, provide symbolic enactments
      of transformation of previously shattered relationships, and reestablish
      connections among family and with society in general. Four ceremonies used with
      Vietnam combat veterans are described which focus on the themes of separation
      from and return to the family, forgiveness of the living, and releasing the dead.
      Ritual and ceremony are highly efficient vehicles for accessing and containing
      intense emotions evoked by traumatic experience. Evaluation by family and
      veterans judge these ceremonies to be the most effective components of treatment.

PMID- 7627445
TI  - Trauma symptoms and PTSD-like profiles in perpetrators of intimate abuse.
AB  - The presence of chronic trauma symptoms and similarity to a specific profile for
      post-traumatic stress disorder (PTSD) were assessed in a group 132 wife
      assaultive men and 44 demographically matched controls. Men who committed
      intimate abuse experienced more chronic trauma symptoms than nonabusive controls.
      A composite profile on the MCMI-II for wife assaulters demonstrated peaks on 82C
      (negative/avoidant/borderline), as have two independent studies of the profile of
      men diagnosed with PTSD. However, the assaultive population had higher scores on
      the antisocial personality scale and lower scores on anxiety and dysthymia. This
      PTSD-like profile on the MCMI-II was associated significantly with more frequent
      anger and emotional abuse of the subject's partner. The trauma origin for these
      men may have been parental treatment: experiencing frequent trauma symptoms as an
      adult was significantly related to negative recollections of parental treatment,
      specifically parental coldness/rejection and physical abuse.

PMID- 7627446
TI  - Post-traumatic stress and associated disorders among Vietnam veterans: the
      significance of combat exposure and social support.
AB  - The hypothesis is tested that individuals exposed to traumatic stress who
      currently have lower social support have higher rates of post-traumatic stress
      and associated disorders. To test this, the current prevalence of five
      psychiatric disorders, including post-traumatic stress, generalized anxiety,
      depression, alcohol abuse, and drug abuse, were studied among a random sample of
      veterans who served in Vietnam (N = 2,490) and a random sample of "era" veterans
      who did not (N = 1,972). Logistic regression was used to analyze each disorder,
      controlling for past combat exposure, current social status, childhood
      delinquency, military adjustment, and current social support. Combat exposure was
      the best predictor of post-traumatic stress and was also associated with anxiety
      and depression, but not alcohol or drug abuse. Substance abuse was associated
      with childhood delinquency, and the best predictor of drug abuse was illicit Army
      drug use. Lower social support was associated with all disorders, except drug
      abuse. Although the causal nexus is not clear in this case, this study suggests
      that future research and clinical interventions should not overlook the
      significance of social support among victims of traumatic stress.

PMID- 7627447
TI  - Treatment of Vietnam War veterans with PTSD: a comparison of eye movement
      desensitization and reprocessing, biofeedback, and relaxation training.
AB  - Analyses of scaled self-report data from Vietnam War veterans receiving inpatient
      treatment for Post-Traumatic Stress Disorder drawn during a program evaluation
      study suggested inpatient treatment as provided by the program resulted in
      significant improvement in the areas of Anxiety, Anger, Depression, Isolation,
      Intrusive Thoughts (of combat experiences), Flashbacks, Nightmares (of combat
      experiences), and Relationship Problems. Comparing the relative effects of the
      incremental addition of Eye Movement Desensitization and Reprocessing (EMDR),
      Relaxation Training, and Biofeedback found that EMDR was for most problems the
      most effective extra treatment, greatly increasing the positive impact of the
      treatment program.

PMID- 7627448
TI  - Gruesomeness, emotional attachment, and personal threat: dimensions of the
      anticipated stress of body recovery.
AB  - Previous research has shown that exposure to grotesque death has been associated
      with posttraumatic stress disorder and higher levels of stress have been
      associated with mortuary workers who anticipated handling remains than those who
      did not. Additional research is presented here to further clarify the nature of
      the anticipated stress of handling the dead. Anticipated stress of handling human
      remains was rated for 13 different situations by 479 persons (384 men and 95
      women) without such experience, but whose job was likely to require it. Factor
      analysis of their ratings revealed three psychological dimensions: the
      gruesomeness of the remains, an emotional link between the viewer and the
      remains, and personal threats to the remains handler. Suggestions for preventive
      measures, training, and interventions for those who may handle remains are made.

PMID- 7627449
TI  - Concepts of normal bereavement: a response.

PMID- 7627450
TI  - Induction with OKT3 and prostaglandin E1 in liver transplantation.
AB  - Forty-six consecutive adult patients underwent 51 orthotopic liver transplants in
      a prospective study to evaluate sequential induction with ORTHOCLONE OKT3
      (muromonab-CD3), prostaglandin E1, cyclosporine, azathioprine, and
      methylprednisolone. Infection prophylaxis included preoperative bowel preparation
      and ganciclovir if cytomegalovirus was diagnosed in either donor or recipient.
      All rejection episodes were documented by liver biopsy before treatment. Seventy
      four percent of patients evaluable beyond 1 year have had no rejection episodes.
      The retransplant rate was 10%, with a 4% primary nonfunction rate. There was no
      rejection of grafts that could not be retreated with OKT3. Forty-two percent (5
      of 12) of rejection episodes responded to steroid recycling alone. The infection
      rates for all patients at 1 year were 54% bacterial, 17% fungal, and 22% viral.
      Three septic deaths were attributed to overimmunosuppression. Two-year patient
      and graft survival rates were 80% and 72%, respectively. This OKT3 induction
      protocol results in limited rejection episodes without increasing infections,
      yielding an acceptably low rate of graft loss.

PMID- 7627451
TI  - Induction therapy with OKT3 in pediatric liver-transplant recipients.
AB  - The goal of any posttransplant immunosuppressive regimen is to prevent allograft
      rejection while minimizing infectious complications. We hypothesized that
      sequential induction immunotherapy using the monoclonal antibody ORTHOCLONE OKT3
      (muromonab-CD3) would meet these objectives effectively. We have therefore used
      such a protocol since July 1988 for all pediatric patients undergoing liver
      transplantation at Children's Hospital Medical Center of Cincinnati. Initial
      immunotherapy consisted of OKT3, administered preoperatively and then QD,
      methylprednisolone, and azathioprine. Cyclosporine was begun on POD 3-5, and OKT3
      was discontinued when therapeutic cyclosporine levels were achieved for 48 hours.
      Rejection has not occurred throughout the lifetime of the allograft in 55% of
      long-term survivors. In the 28 patients who experienced rejection episodes, 71%
      had a single episode, 21% had two episodes, and 7% had a single episode, 21% had
      two episodes, and 7% had more than two. Rejection occurring after more than 120
      days was invariably associated with noncompliance or subtherapeutic cyclosporine
      levels. The use of an OKT3-based sequential induction protocol resulted in a
      decreased incidence of acute rejection. Renal function was preserved, and the
      incidence of infection was not increased. Long-term outcome analysis of this
      protocol shows excellent patient survival and the near absence of late or chronic
      rejection.

PMID- 7627452
TI  - Cytokines and transplantation: a clinical perspective.
AB  - Cytokines are endogenous small peptides that regulate cell growth and
      proliferation. In allogeneic transplantation, they function as critical
      immunologic mediators. Allograft rejection is dependent on interactions between
      antigen-presenting cells, T lymphocytes, accessory molecules, and proinflammatory
      cytokines (interleukins-1, -2, and -6; interferon-gamma; and tumor necrosis
      factors). Alternatively, other cytokines (interleukins-4, -5, and -10;
      transforming growth factor-beta) may suppress allograft rejection. Observation
      and manipulation of cytokine responses are an essential component of the
      immunopharmacology and clinical management of transplant recipients. Specific
      areas of interest include immunologic monitoring, pharmacologic
      immunosuppression, monoclonal antibody development, induction of tolerance, and
      the OKT3-related cytokine release syndrome. This review explores the impact of
      advances in cytokine physiology and biotechnology on clinical transplantation.

PMID- 7627453
TI  - Cell penetration of bacterial protein toxins.

PMID- 7627455
TI  - Recent insights into the biology of the human foamy virus.
AB  - Human foamy virus (HFV) is a complex retrovirus with structural similarities to
      HIV and human T cell leukemia virus. There have been considerable advances in
      understanding the biology of HFV in cell cultures. However, viral behavior in
      vivo, and even viral detection, are still poorly understood. While HFV-transgenic
      mice develop neuromuscular disorders, attempts to associate HFV with a specific
      human disease have given inconclusive results.

PMID- 7627454
TI  - The complex flagella of gastric Helicobacter species.

PMID- 7627456
TI  - Epidemic spread and antigenic variability of Neisseria meningitidis.
AB  - Genetic variation of cell-surface antigens of serogroup A meningococci arises
      from horizontal genetic exchange. Most clonal variants are lost by clonal
      reduction during epidemic and pandemic spread, but in exceptional cases, genetic
      variants are rapidly fixed in the bacterial population by clonal replacement.

PMID- 7627457
TI  - Regulation of extracellular toxin production in Clostridium perfringens.
AB  - Until recently, little was known about the regulation of toxin production in
      Clostridium perfringens. Three regulatory genes that control the production of
      theta toxin (perfringolysin O) have now been identified. Two of these genes make
      up a two-component sensor-kinase-response-regulator system that also controls the
      production of other extracellular toxins.

PMID- 7627458
TI  - Recognition and control of neisserial infection by antibody and complement.
AB  - Immunity to neisserial infection involves complex interactions between antibody,
      complement and bacterial cell-surface molecules. Neisseria species express
      polysaccharide and glycolipid membrane components, which downregulate complement
      activation. The pathogenic potential of Neisseria depends on evasion of the
      complement cascade.

PMID- 7627459
TI  - Horizontal transfer in the phytopathogenic fungal genus Leptosphaeria and host
      range expansion.
AB  - All isolates examined of the phytopathogenic fungus Leptosphaeria maculans that
      are aggressive to Brassica napus and Brassica rapa have a repetitive element,
      LMR1. Horizontal transfer of LMR1 to an isolate of a closely related species of
      Leptosphaeria correlates with the expansion of the host range of this isolate to
      include Brassica juncea.

PMID- 7627460
TI  - Controversial referrals.

PMID- 7627461
TI  - Secondment comes first.

PMID- 7627462
TI  - Near-site for the vision.

PMID- 7627463
TI  - New clear vision?

PMID- 7627464
TI  - Redundancy life rafts.

PMID- 7627465
TI  - Peril washes whiter.

PMID- 7627466
TI  - Pick and mix.

PMID- 7627467
TI  - A yawning gulf between educationalists and nursing managers.

PMID- 7627468
TI  - Council the profession.

PMID- 7627469
TI  - Community nursing's death by social care.

PMID- 7627470
TI  - Mental health of culturally diverse clients.

PMID- 7627471
TI  - Review of the literature on African American caregivers of individuals with
      dementia.
AB  - Despite the large body of literature on caregivers for relatives with dementia,
      few studies have included minority caregivers. This paper examines research
      studies on African American caregivers of relatives with dementia and provides
      recommendations for future research.

PMID- 7627472
TI  - Accent, skin color and information processing errors in a clinical analogue.
AB  - This study explored ethnic bias in psychotherapy with a videotaped analogue
      design in which accent and skin color were manipulated while holding all other
      factors constant. One hundred and eighty-nine White students viewed one of four
      videotapes and provided ratings of the client. ANOVA yielded significant main
      effects for accent, no main effects for skin color, nor interactions. Accent
      influenced ratings of skin color, ethnic identity, social class, education and
      linguistic background. The client was rated significantly more disturbed and in
      more urgent need of mental health treatment when presented in an Hispanic than a
      White ethnic guise.

PMID- 7627473
TI  - Rural Mexican-American and non-Hispanic white women: effects of abuse on self
      concept.
AB  - This research arose from clinical practice in a rural Mexican-American and non
      Hispanic white community in Southwest Texas. The practice focused on individual
      and group counseling for these women in abusive relationships. Effects of type of
      abuse (physical, sexual, psychological) on self-concept were identified. Rural
      Mexican-American and non-Hispanic white women experiencing sexual abuse versus
      other forms of abuse were found to have significantly lower perceptions of
      competency on a multi-dimensional measure of self-concept. Ethnic differences in
      self-concept were also found between groups of abused, rural Mexican-American and
      non-Hispanic white women.

PMID- 7627474
TI  - Stress, women and weight control behavior.
AB  - This study explores the relationship between stress and weight control behavior
      in four groups of women: African American, European American, Mexican/Mexican
      American, and Puerto Rican. Data were collected on 111 women between the ages of
      23 and 75 using a between-methods triangulation approach in which interview and
      questionnaire data were collected. The women were involved in various types and
      levels of weight control behavior. Although all the women identified occupational
      and major life stressors, only European American women's weight control behavior
      was significantly related to stress.

PMID- 7627475
TI  - Radioactive iodine as a diagnostic aid for intrathoracic goitre. 1948.

PMID- 7627476
TI  - Invited review: the early years of radiotherapy with emphasis on X-ray and radium
      apparatus.
AB  - Radiotherapy apparatus, both X-ray and radium, is reviewed for the first 4
      decades of this century and the developments during this period are outlined,
      emphasizing the more important growth points. Radiation dose measurement units
      and radiation protection features of equipment are also included.

PMID- 7627477
TI  - Fractures of the lateral process of the talus--the value of lateral tomography.
AB  - We present three cases of fractures of the lateral process of the talus, where
      routine anteroposterior and lateral radiographs showed an abnormality but were
      insufficient to assess the degree of bony injury, which is important for clinical
      management. Lateral tomography provided good diagnostic and anatomical detail.
      The diagnosis and treatment of this unusual and often missed fracture is
      discussed.

PMID- 7627478
TI  - The role of duplex and colour Doppler ultrasound in the follow-up evaluation of
      transjugular intrahepatic portosystemic stent shunt (TIPSS).
AB  - Transjugular intrahepatic portosystemic stent shunt (TIPSS) is an effective means
      of controlling acute variceal haemorrhage. Shunt occlusion or stenosis occurs in
      up to 30% of patients within 6 months. It is important to detect these patients
      and intervene to prevent rebleeding. We have compared non-invasive Doppler
      ultrasound with the portal pressure gradient (PPG) at portography at 3 month
      follow-up in 23 patients. All patients with a shunt peak velocity greater than 90
      cm s-1 (7 of 17 analysable results) had normal shunt function at portography (PPG
      < 12 mmHg). Portography may therefore be avoided in this group, although the
      majority of patients will still require portography for TIPSS follow-up
      assessment.

PMID- 7627479
TI  - Long-term venous access service based in the barium room.
AB  - 27 totally implantable venous access devices (ports), 12 long term dual-lumen
      venous access catheters and one tunnelled long line were placed over 13 months in
      a standard district general hospital (DGH) screening room. No significant early
      complications occurred. Two patients referred from outside hospitals were lost to
      follow-up. Of the 38 lines with comprehensive follow-up, three required removal
      because of suspected infection and one because of thrombosis giving a major
      complication rate of 4 per 6800 access days, i.e. 0.59 per 1000 access days. The
      minor complications comprised five treatable infections and one resolving
      subclavian thrombosis in 6800 access days. These rates compare favourably with
      previous radiological series in which procedures were performed in "clean"
      vascular suites, and with previous surgical series. Radiological insertion of
      these devices with rapid scheduling and local anaesthesia methods is feasible in
      a DGH without the use of a specialized vascular suite.

PMID- 7627480
TI  - Comparison of light reflection rheography with ascending venography in the
      diagnosis of lower limb deep venous thrombosis.
AB  - A prospective evaluation of light reflective rheography (LRR) in the diagnosis of
      acute lower limb deep venous thrombosis (DVT) has been conducted by the
      comparison of rheographic changes with ascending venography. LRR reliably
      predicts the absence of DVT, but cannot accurately detect its presence. It is
      suggested that the technique may be used for surveillance but should not replace
      venography as a method for establishing the diagnosis of DVT.

PMID- 7627481
TI  - The prevalence of cervical and thoracic congenital skeletal abnormalities in
      basal cell naevus syndrome; a review of cervical and chest radiographs in 80
      patients with BCNS.
AB  - The major clinical stigmata of basal cell naevus syndrome (BCNS) appear in
      adolescence and adult life but some occult skeletal abnormalities are congenital.
      BCNS is dominantly inherited and it would be useful to identify, as early in life
      as possible, which of the offspring of patients with BCNS are at risk of
      developing the syndrome. Radiographs of the neck and chest of 80 patients with
      BCNS diagnosed confidently on clinical criteria have been examined for
      abnormalities which were considered to be congenital skeletal anomalies.
      Congenital abnormalities of the cervical and thoracic spine, mainly spina bifida
      occulta, were found in 45%. Congenital abnormalities of ribs were found in 49%
      and of the shoulder(s) in 36%. Overall congenital abnormalities were shown on the
      neck or chest radiograph in 55 (69%) patients. The presence of one or more of
      these congenital abnormalities on the chest or neck radiograph of a child who is
      the offspring of a person with BCNS makes it extremely likely that the child also
      has BCNS. The absence of these features, and of any clinical features of BCNS,
      would suggest that the risk of the child developing BCNS has been reduced from
      the prior expectation of 50% to approximately half that (24%).

PMID- 7627482
TI  - Computerized axial tomographic scan measurements as prognostic indicators in
      patients with cervical carcinoma.
AB  - This retrospective study of 56 patients with carcinoma of the uterine cervix
      treated with radical radiotherapy at the Royal Marsden Hospital, London, examined
      whether simple measurements of maximum tumour dimension from computerized axial
      tomographic (CT) scans have any prognostic significance. Our results indicate
      that tumour depth (i.e. maximum antero-posterior dimension) of 4 cm or more is
      associated with a statistically significant increased relative risk of death of
      2.4 (95% CI 1.1-5.5; p = 0.045), as compared with tumours with a depth of less
      than 4 cm. In addition, there was a clear correlation between tumour depth and
      lymph node involvement (r = 0.36; p < 0.01), and tumour depth and width (r =
      0.70; p < 0.005). We suggest that a measurement of maximum tumour depth from the
      staging CT scan in these patients provides valuable additional information about
      likely occult lymph node metastases and prognosis, over and above that suggested
      by the FIGO staging system alone.

PMID- 7627483
TI  - The radiation dose to children from X-ray examinations of the pelvis and the
      urinary tract.
AB  - X-ray examinations of the pelvis and the urinary tract are frequent examinations
      of children, in which a large part of the trunk is irradiated. The irradiated
      volume contains many of the most radiation sensitive organs and tissues. The
      absorbed dose to children during the examination was estimated from measurements
      with a dose-area product meter and thermoluminescent dosemeters (TLDs). Entrance
      surface dose and the dose-area product results are presented. Conversion factors
      between the entrance surface dose and the organ dose were derived. The energy
      imparted, organ dose and effective dose were determined. The entrance surface
      dose for one single exposure varied between 0.32 mGy and 8.6 mGy for the urinary
      tract examination and between 0.26 mGy and 2.89 mGy per exposure for the pelvis
      examination. These variations are mainly influenced by the body size of the
      patient. The number of images taken during one examination varied. For the
      urinary tract investigation, the average number of exposures was six, while the
      corresponding number for the pelvis examination was two. The average effective
      dose for a typical urinary tract investigation ranged from 0.9 mSv to 8.5 mSv and
      from 0.3 mSv to 1.4 mSv for the pelvis examination. The radiation dose depends
      greatly on the body size. The recommendations to present the results in relation
      to age have been followed; however, the variation of body size even within each
      specified age range is significant. It is suggested that doses should be quoted
      in relation to a more critical parameter than age.

PMID- 7627484
TI  - Vertebral fractures in men and women: how discriminative are bone mass
      measurements?
AB  - Vertebral fractures are associated with osteoporosis. This study examined men and
      women with vertebral deformation/fractures, as defined by vertebral morphometry.
      These were compared with a population derived group measured contemporaneously
      who were defined as having no vertebral deformation/fracture by the radiographs.
      All patients underwent a dual energy X-ray absorptiometry (DXA) scan of the spine
      and hip, and a broadband ultrasound attenuation (BUA) scan of their os calcis.
      The abilities of these two techniques were compared for their discriminatory
      powers in this type of fracture. The results showed that DXA hip and spine had a
      better discriminatory power in the female vertebral group compared with BUA. In
      males none of the bone measurements could discriminate between the fracture and
      non-fracture groups.

PMID- 7627485
TI  - Comparisons between three dual-energy X-ray absorptiometers used for measuring
      spine and femur.
AB  - Lunar, Hologic and Norland dual-energy X-ray absorptiometry scanners have been
      compared for measurements of spine and femur bone density. Precision was not
      greatly different in realistic phantoms and volunteer subjects. Most clinical
      therapeutic trials are concerned with measuring changes of bone mineral, and
      interchangeability in this context was examined using phantoms of spine and femur
      in which changes of bone mineral density (BMD) were simulated. With each
      instrument the measured changes were closely linear. For the spine the biggest
      difference of slope between instruments was 15%. For the femur, in all areas of
      interest, the differences of slope were less than 10%. It is concluded that the
      three instruments can be satisfactorily used in multicentre clinical trials to
      investigate changes in bone mineral. 12 volunteers were measured with each
      scanner. There were significant mean differences between each pair of
      instruments, suggesting different calibration criteria. More importantly, those
      mean differences had appreciable standard deviations (SDs), in proportional terms
      from 3% to 10%. When the measurements were related to reference ranges and
      expressed in terms of age-matched normal values the mean biases disappeared, but
      the SDs did not improve. Results from different manufacturers' apparatus are not
      interchangeable for studying individual patients. Measurements from the phantoms
      were used to cross-calibrate the scanners. Those from the variable spine phantom
      predicted the in vivo ratio within 4%, but this was no better than measurements
      of the unmodified phantom alone. Results using the European Spine Phantom were
      less satisfactory. No phantom provided an adequate cross-calibration for femur
      measurements.

PMID- 7627486
TI  - External and interstitial radiotherapy in the treatment of oropharyngeal squamous
      cell carcinoma.
AB  - The records of 165 patients with squamous cell carcinoma of the oropharynx
      treated at our hospital with external and/or interstitial radiotherapy between
      1971 and 1990 were reviewed to evaluate the treatment results, focusing on
      primary control and complications. All cancers were restaged according to the
      UICC 1987 TNM staging system. Of these 165 patients, 11% were in Stage I, 55% in
      Stage II, 24% in Stage III and 8.5% in Stage IV. Local control and complications
      were analysed in 140 patients. The remaining 25 patients died of intercurrent or
      metastatic disease during the first 2 years following treatment and were excluded
      from the analysis. 70 patients were treated by interstitial implant using
      permanent implant seeds (Rn-222 in eight patients, Au-198 in 62 patients) with or
      without external radiation. 56 other patients received external irradiation alone
      and another 14 patients received pre-operative external irradiation plus surgery.
      2-year recurrence-free rates were 73% (100% for T1, 76% for T2, 36% for T3
      tumours) in the patients who received interstitial implant with or without
      external radiation and 36% (67% for T1, 48% for T2, 13% for T3 tumours) in the
      patients treated by external irradiation alone. The incidence of soft-tissue or
      bone complications requiring long-term treatment was 14%. Based on these
      findings, it is believed that an interstitial implant using Au-198 grains
      combined with external beam irradiation is a useful treatment modality for small
      lesions of the oropharynx.

PMID- 7627487
TI  - Model based calculation for effective cancer radioimmunotherapy.
AB  - The major problem of tumour radioimmunotherapy remains the low tumour antibody
      uptake and this leads to inadequate tumour irradiation. The antibody
      characteristics which influence uptake have been identified and quantified
      previously using a non-linear compartmental model that simulates antibody
      distribution to tumour and body after intravenous injection. The model has now
      been extended, in combination with MIRD dosimetry tables, to calculate the
      integral tumour/body radiation dose for a range of antibody masses (1, 10 and 50
      mg), sizes (binding site fragments and whole molecules) and affinities (K = 10(9)
      10(13) mol-1). Antibody requirements for delivering 60 Gy to the tumour over 11.6
      days were calculated for 131I and 90Y-labelled antibodies and included the effect
      of widely varying dose rates. The model predicted that intact antibodies of high
      affinity (10(11)-10(13) mol-1) produced effective tumour radiation doses with
      acceptable whole body radiation levels. By contrast, antibody fragments gave
      higher body radiation levels and required larger injected activity because of
      renal excretion. The model predicted higher therapeutic indices for 90Y-labelled
      antibody compared with 131I.

PMID- 7627488
TI  - Technical note: the efficacy of megavoltage imaging in the radical radiotherapy
      of non-small cell lung cancer.
AB  - Megavoltage imaging (MVI) has been used to obtain digital images of treatment
      fields during therapy for non-small cell lung cancer. Tumours were seen in all 33
      cases studied and in three cases MVI was used to improve the set-up. It is
      concluded that in the setting of radical radiotherapy for non-small cell lung
      cancer this is an appropriate technique for the verification and correction of
      field position and is an aid to quality assurance.

PMID- 7627489
TI  - Technical note: computed tomography imaging with a radiotherapy simulator.
AB  - An inexpensive system for obtaining cross-sectional information and accurate body
      outlines of patients destined for radiotherapy, using a radiotherapy simulator
      without any major modifications, has been investigated. The image intensifier of
      the simulator was moved laterally and a narrow fan beam of X-rays passed through
      the phantom onto the intensifier. Several television (TV) lines of the video
      signal from the TV camera were digitized by a frame grabber and stored for
      reconstruction. Multiple projections were acquired by rotating the gantry of the
      simulator. The field of view was enlarged by increasing the offset distance of
      the image intensifier and taking two sets of projections. Reconstruction was
      carried out by using the convolution and back-projection method. The gradient
      between pixel values in the reconstructed images was used to detect the outlines
      of structures in the images. The accuracy of outline detection was evaluated with
      images of a Rando phantom. The outlines of the images were compared with the
      actual outlines of the phantom. The spatial resolution of the simulator computed
      tomography (CT) was measured to be 4.05 mm. Large inhomogeneities could be
      clearly seen. The average difference between the measured and the actual outlines
      was 3.0 mm with a maximum difference of 10.0 mm at sharp curves in the outline.
      The simulator CT provides an inexpensive, alternative method of obtaining body
      outlines and does not require any modifications to the simulator. Data
      acquisition, processing and display can be performed on a personal computer with
      image processing facilities.

PMID- 7627490
TI  - Case report: the demonstration of aortocaval fistulae by helical computed
      tomography.
AB  - We report the helical computed tomography findings in two patients with
      spontaneous aortocaval fistula (ACF) complicating abdominal aortic aneurysm. The
      use of overlapping slices produced high quality multiplanar reformats which
      provided anatomical information about the likely site of the ACF and also the
      relationship of the renal arteries to the neck of the aneurysm.

PMID- 7627491
TI  - Case report: mesenteric mixed haemangioma and lymphangioma; report of a case with
      10 year follow-up after radiation treatment.
AB  - A patient with massive mixed haemangioma and lymphangioma of the mesentery first
      presented in childhood with ascites which subsided spontaneously and,
      subsequently, at 21 years of age, presented with gastrointestinal bleeding. At
      laparotomy, the lesion was found to involve 90% of the mesentery and was
      unresectable due to its bulk. Hence he was treated by radiotherapy (15 Gy/15
      fractions/3 weeks followed by a boost of 5 Gy/4 fractions/4 days). He responded
      to the treatment. 10 years later he again experienced mild gastrointestinal
      bleeding which subsided spontaneously. This case illustrates the efficacy of
      radiotherapy in massive mesenteric haemolymphangiomas. Review of the literature
      revealed that surgical excision, embolization, and radiotherapy have been used in
      the treatment of haemangiomas and lymphangiomas. In unresectable cases,
      radiotherapy has a definite role in the management. A variety of doses has been
      employed in the literature. No definite dose-response relationship was
      identified.

PMID- 7627492
TI  - Case report: computed tomography features of complete splenic infarction,
      cavitation and spontaneous decompression complicating pancreatitis.
AB  - Splenic infarction is a rare complication of pancreatitis. We present the case of
      a 34-year-old woman, who had undergone previous drainage of a pancreatic
      pseudocyst, and who represented with left upper quadrant pain. Absence of
      enhancement of the splenic parenchyma during contrast enhanced computed
      tomography (CT) allowed confident diagnosis of complete splenic infarction. A
      later CT scan revealed splenic cavitation with spontaneous decompression into the
      stomach. The aetiology of these unusual complications of pancreatitis is
      discussed.

PMID- 7627493
TI  - Case of the month: a single diagnosis: that is the question.

PMID- 7627494
TI  - Short communication: a lateral will do?
AB  - Efforts to reduce the dose of diagnostic medical irradiation by applying
      selective criteria for radiographic examinations have been addressed by the Royal
      College of Radiologists in their Guidelines. Reduction of the number of views of
      an area has also been suggested by some authors. Deviating from one of the
      fundamentals of skeletal radiology which requires at least two views of any part
      of the skeleton may lead to misdiagnosis. This concept is considered in relation
      to the lumbar spine. Continued routine acquisition of at least two views for the
      radiographic examination of the lumbar spine is stressed.

PMID- 7627495
TI  - Field matching in craniospinal irradiation.

PMID- 7627496
TI  - Adjuvant biological response modifiers after major surgery or trauma.

PMID- 7627497
TI  - Thromboprophylaxis in malignant disease.

PMID- 7627498
TI  - Homocysteine and vascular disease.
AB  - There is increasing evidence that a raised blood level of homocysteine (HC) is a
      risk factor for premature atherosclerosis. With a gene frequency between one in
      70 and one in 200 this condition may be more common than previously thought. It
      should be suspected especially in young patients in whom other risk factors are
      absent. The diagnosis may be made by demonstrating raised plasma HC levels,
      either basally or after methionine loading. Studies have shown significantly
      increased levels of HC in patients with premature coronary artery, peripheral
      vascular and cerebrovascular disease. The mechanisms by which HC produces
      vascular damage are, as yet, not completely understood but endothelial injury is
      probably a central factor. The principle of treatment is to lower HC levels in
      the blood by administration of vitamin B6, vitamin B12, folate or betaine. How
      effective this strategy will be in preventing complications is not yet known.

PMID- 7627499
TI  - Surgical treatment of morbid obesity.
AB  - Morbid obesity significantly reduces life span and is associated with much co
      morbid pathology. Diet, behavioural therapy and drug therapy are largely
      unsuccessful. Surgical treatment offers the best hope. This review summarizes the
      rationale for treatment and the available surgical options.

PMID- 7627500
TI  - Surgical management of rectal cancer.

PMID- 7627501
TI  - Endoloop: a helpful new device for transanal rectal polypectomy.

PMID- 7627502
TI  - Efficacy of glutamine-enriched enteral nutrition in an experimental model of
      mucosal ulcerative colitis.
AB  - Intact intestinal epithelium and associated lymphatic tissue act as body defences
      against luminal toxins. This barrier may become threatened or compromised in
      inflammatory bowel disease, leading to an increase in mucosal permeability and
      subsequent translocation of endotoxins. The effect of oral glutamine on gut
      mucosal ornithine decarboxylase activity and on endotoxin levels in portal vein
      blood was studied in a guinea-pig model of carrageenan-induced colitis. Despite
      failure to show induction of ornithine decarboxylase activity by glutamine
      administration, the mean endotoxin level of portal vein blood in guinea-pigs fed
      a glutamine-enriched elemental diet was 25.3 pg/ml compared with 71.2 pg/ml in
      animals given a standard elemental diet (P < 0.01). A glutamine-enriched
      elemental diet may be therapeutically beneficial in patients with inflammatory
      bowel disease.

PMID- 7627503
TI  - Total excision versus non-resectional methods in the treatment of acute and
      chronic pilonidal disease.

PMID- 7627504
TI  - Anterior rectal mucosal prolapse: an easily treated cause of anorectal symptoms.

PMID- 7627505
TI  - Synchronous proctocolectomy and ileoanal pouch formation and the risk of Crohn's
      disease.
AB  - There is controversy on the advisability of one-stage proctocolectomy and the
      formation of an ileoanal pouch. Accurate preoperative diagnosis is essential to
      avoid the error of constructing a pouch in a patient with Crohn's disease. Twenty
      four consecutive patients undergoing subtotal colectomy for inflammatory bowel
      disease were reviewed. All patients had been treated with systemic steroids, 23
      were on 5-aminosalicylates and 11 on azathioprine. The preoperative diagnoses,
      based on a combination of clinical features, colonoscopy, barium enema and biopsy
      histology, were ulcerative colitis (19), Crohn's disease (four) and inflammatory
      bowel disease (unclassified) (one). The final diagnosis was made on histological
      examination of the resected specimen. A discrepancy between initial and final
      diagnosis occurred in eight patients. In three, the diagnosis was changed from
      ulcerative colitis to Crohn's disease. Three preoperative diagnoses of Crohn's
      disease were changed to ulcerative colitis (one), Behcet's disease (one) and
      diverticulitis (one) on final histology. These data suggest that caution should
      be exercised in performing synchronous proctocolectomy with the formation of an
      ileoanal pouch.

PMID- 7627506
TI  - Lysis-assisted angioplasty in the treatment of lower-limb arterial thrombosis.
AB  - This study examined the results in 30 patients treated with lysis-assisted
      angioplasty and compared them with the results of 30 patients with simple
      stenotic disease treated by angioplasty alone. One patient died on the day of
      treatment with lysis-assisted angioplasty from arterial perforation and
      haemorrhage. Of the remaining 29 patients 16 (55 per cent) were symptomatically
      improved and 13 had early reocclusion. Six patients developed major complications
      (two deaths, two major haemorrhage, two cerebrovascular accident). The late
      results were comparable to those for patients undergoing angioplasty alone. The
      best outcome was obtained in patients with proximal disease (P < 0.01); poor run
      off or critical ischaemia did not preclude a good outcome.

PMID- 7627507
TI  - Clinical and experimental studies of intraoperative autotransfusion using a new
      filtration device.
AB  - The Haemocell S-350 device has recently been introduced for intraoperative
      autotransfusion. The system uses a novel membrane filter to process shed blood.
      In the first part of this study a 0.2-micron pore size filter was used in a
      randomized trial comparing the use of autotransfusion (n = 8) with bank blood
      controls (n = 9) during aortic reconstruction. This part of the trial was
      abandoned because of unexpected non-surgical bleeding. Bank blood requirements
      fell from a median of 3.0 (range 0.0-9.0) units to 1.5 (range 0.0-7.0) units when
      autotransfusion was used, but these patients had a greater perioperative blood
      loss (1791 (range 932-3104) versus 1140 (range 440-3840) ml). There was evidence
      of postoperative heparin excess with an activated partial thromboplastin time
      ratio of 1.3 (range 0.9-3.0) versus 1.0 (range 1.0-1.2) in controls and an
      activated clotting time of 206 (range 143-280) versus 137 (range 107-142) s. This
      was confirmed by raised plasma heparin levels and a prolonged thrombin time
      normalized by protamine. To improve performance a 0.6-micron pore size filter was
      studied in ten patients. Filtration efficiency doubled from 19 to 38 per cent.
      Electron micrographs demonstrated better filter clearance, but 44 per cent of the
      original concentration of heparin remained in the reinfusate. The S-350 device
      may be an attractive alternative to centrifugation for intraoperative
      autotransfusion but, until efficiency is improved, it should only be used for
      cardiovascular surgery when excess heparin can be reversed with protamine.

PMID- 7627508
TI  - Granulocyte-macrophage colony-stimulating factor modulates immune function and
      improves survival after experimental thermal injury.
AB  - Thermal injury is associated with reduced colony-stimulating activity, which
      correlates with increased susceptibility to infection. To assess the effect of
      therapeutic administration of granulocyte-macrophage colony-stimulating factor
      (GM-CSF), 8-week old anaesthetized mice were subjected to either a 20 per cent
      body surface burn or a sham burn. Animals were subsequently treated with either
      vehicle or a range of doses of GM-CSF (10-1000 ng) with or without indomethacin
      (5 micrograms). Sepsis was induced by caecal ligation and puncture on day 10
      after injury. Survival was significantly better in animals treated with 200 ng GM
      CSF on days 5-9 after the burn. Concanavalin A-stimulated T cell proliferation
      and interleukin (IL) 2 production were significantly depressed after burn injury.
      In vivo therapy with 200 ng GM-CSF, however, led to a significant improvement in
      both of these parameters of T cell function. These data suggest that GM-CSF has a
      potential therapeutic role in the prevention of death from burn sepsis and
      appears to act, at least in part, by restoring defective T cell proliferation and
      IL-2 production.

PMID- 7627509
TI  - War injuries of the crural arteries.
AB  - Twenty-eight patients with military crural vascular injuries are presented. In
      the group undergoing immediate repair (21 patients), the time interval between
      trauma and surgery was 20 min to 30 h (mean 8 h 30 min). In those receiving
      delayed repair (seven patients), the interval between trauma and surgery was 3-47
      (mean 14) days. Hyperbaric oxygenation therapy was used in conjunction with
      surgery and antibiotic therapy in 13 of the 28 patients. Explosive injuries were
      found in 14 patients and high-velocity missile injuries in nine; associated
      fractures were present in 20. Twenty of the 28 patients with crural vascular
      injuries had combined arterial and venous injuries, while eight had isolated
      arterial injuries. Twenty-five patients with distal ischaemia required arterial
      repair; five late amputations resulted. Military crural vascular injuries should
      be treated with soft tissue debridement, removal of foreign material, and
      microvascular arterial and concomitant vein reconstruction. This should be
      followed by external skeletal stabilization for bony and/or soft tissue
      instability, with fasciotomy for any associated compartment syndrome. The wound
      should be left open, with delayed closure or split skin grafting. It was felt
      that hyperbaric oxygen therapy reduced the amputation rate following combat
      related crural vessel injuries.

PMID- 7627510
TI  - Differences in body temperature changes during dressing change in surviving and
      non-surviving burned patients.
AB  - Change in body temperature (delta BT) while dressings were being changed was
      measured in 52 extensively burned adults. The patients were divided into four
      groups based on outcome and the prognostic burn index (PBI; age + burn index):
      group I (15 survivors, PBI less than or equal to 80), group II (15 survivors, PBI
      between 80 and 120), group III (14 non-survivors, PBI between 80 and 120), and
      group IV (eight non-survivors, PBI greater than 120). The body temperature before
      the change of dressings was the same in the four groups. The mean(s.d.) delta BT
      in all patients was -0.5(0.8) degrees C. The magnitude of delta BT was not
      related to the time required for changing dressings (r = 0.04) or to the non
      epithelialized area present at each change of dressings (r = -0.05). All groups
      showed a similar increase in delta BT during the early period after the burn, but
      in group I it began to decrease progressively after the 16th day after the burn
      (P < 0.05). A reduction in delta BT was noted in group II from day 25, whereas it
      was unchanged in groups III and IV (P < 0.05). It also significantly increased 2
      days before the diagnosis of sepsis (P < 0.05). These results emphasize that
      delta BT may provide useful information about prognosis and the development of
      sepsis.

PMID- 7627511
TI  - Blood flow in breast cancer and fibroadenoma estimated by colour Doppler
      ultrasonography.
AB  - Blood flow was measured by colour Doppler ultrasonography in 33 fibroadenomas of
      size 5-31 mm and 28 malignant breast masses of 8-37 mm visible on
      ultrasonography. There was detectable blood flow in 11 fibroadenomas and 21
      cancers (P < 0.01). The median peak systolic frequency was 1.0 (range 0.25-2.0)
      kHz in malignant tumours and 0.5 (range 0.2-1.25) kHz in fibroadenomas. Blood
      flow was not detected in the eight fibroadenomas of less than 13 mm but was
      present in five of seven cancers smaller than this. Five of six carcinomas with
      three or more detectable vessels were classified as grade III on histological
      examination, compared with two of 11 carcinomas with one or two vessels.
      Similarly, five of seven cancers with three or more detectable vessels had
      axillary lymph node metastases compared with two of 13 with only one or two
      vessels. Detectable blood flow in breast masses is more common in cancer than in
      fibroadenoma and is highly suggestive of malignancy if the mass is less than 13
      mm in size. Malignant tumours with a larger number of vessels are more likely to
      be of high grade and to have associated axillary node metastases.

PMID- 7627512
TI  - Exfoliative cytology in the diagnosis of breast disease.
AB  - A total of 393 nipple discharge or scrape smears from 360 women were examined
      cytologically over a 12-year period. Twenty-nine breast cancers (8 per cent) have
      been histologically confirmed in this group, of which 16 had malignant smear
      cytology (sensitivity 55 per cent). Nine patients with breast cancer and positive
      cytology had impalpable tumours. Two of these cancers were not detected by any
      other investigation. Thirteen patients with nipple discharge had false-negative
      cytology, but there were no false-positive results (specificity 100 per cent).
      All patients with expressible or spontaneous nipple discharges and those with
      skin changes at the nipple should undergo examination of cytological smears.

PMID- 7627513
TI  - Non-operative management of breast masses diagnosed as fibroadenoma.
AB  - A 7-9-year study was undertaken in 99 female patients (median age 20 years), 56
      of whom had single and 43 multiple fibroadenomas (total 279). Thirty-four women
      with 58 masses (21 per cent) were lost to follow-up. Twenty-eight women with 73
      masses (26 per cent) subsequently underwent excision at a median of 10 (range 3
      59) months for single and 38 (1-110) months for multiple fibroadenomas (P =
      0.03), with histological confirmation in 71 and other benign disease in two
      cases. There was resolution of 107 masses (38 per cent of those entered into the
      study, 72 per cent of those not lost or excised), leaving 41 persisting masses
      (15 per cent of those entered into the study, 28 per cent of those not lost or
      excised). The actuarial probability of disappearance was 0.46 at 5 years and 0.69
      at 9 years (Kaplan-Meier analysis). There was no difference in the rate of
      resolution when 56 single lesions were compared with 223 multiple lesions, or
      when 192 lesions measuring 2 cm or less in diameter were compared with 87 greater
      than 2 cm. Resolution was significantly more frequent in women aged 20 years or
      less than in those who were older (P < 0.01). Non-operative management remains a
      safe approach in selected women and should be followed by resolution of half of
      fibroadenomas at 5 years.

PMID- 7627515
TI  - Manometric assessment of the effect of the diaphragmatic crural sling in gastro
      oesophageal reflux: implications for surgical management.
AB  - A manometric method to measure the effect of contraction of the crural sling of
      the diaphragm on intraoesophageal pressure is described. The manometric crural
      pressure was measured in 57 patients with gastro-oesophageal reflux disease,
      documented by 24-h ambulatory pH monitoring, and compared between patients with
      and without hiatal hernia. Repeat measurements were made in 33 patients who
      underwent antireflux surgery that incorporated a crural repair. Mean crural
      pressure in 41 patients with hiatal hernia was 5.0 mmHg, compared with 15.0 mmHg
      in 16 without hiatal hernia (P < 0.01). In the 33 patients undergoing antireflux
      surgery, mean crural pressure rose from 7.1 mmHg before operation to 11.6 mmHg
      afterwards (P < 0.02) overall, and from 4.7 to 10.1 mmHg (P < 0.01) in the 26
      patients with hiatal hernia. These results confirm a measurable contribution of
      the diaphragmatic crural sling to resting pressure at the high-pressure zone. The
      crural pressure is deficient in patients with hiatal hernia compared with that in
      those with reflux but no hernia. The mean crural pressure is increased in
      patients by antireflux surgery, particularly in those with hiatal hernia. The
      results provide objective support for the role of the crural diaphragm in the
      antireflux mechanism and the rationale of performing crural repair during
      antireflux surgery, particularly in the presence of hiatal hernia.

PMID- 7627514
TI  - Physiological and symptomatic outcome after laparoscopic gastric fundoplication.
AB  - The complications of open antireflux operations may be reduced by laparoscopic
      techniques. Fifteen patients of median age 42 (range 16-79) years with gastro
      oesophageal reflux underwent laparoscopic fundoplication. Preoperative and
      postoperative assessment was by clinical scoring, oesophageal pH measurement and
      manometry. Median (range) operating time was 115 (60-210) min and hospital stay 3
      (1-6) days, with no conversions to open operation and only one minor wound
      infection. Four patients had occasional reflux symptoms on postoperative
      assessment at a median of 7 weeks and nine had occasional dysphagia. Median
      DeMeester symptom scores improved from 4 to 1.5 (P = 0.001). There were
      significant increases in both lower oesophageal sphincter pressure and length.
      The nocturnal proportion of time at pH < 4 decreased from 9.6 to 0.05 per cent (P
      = 0.02), although the drop in total proportion of time at pH < 4 (10.4 to 2.2 per
      cent) was not statistically significant (P = 0.08). Early objective results of
      laparoscopic fundoplication show improved symptoms, decreased acid reflux and
      altered lower sphincter function. The procedure combines the benefits of early
      mobilization and reduced morbidity with the efficacy of the traditional open
      operation.

PMID- 7627516
TI  - Comparison between resectable gastric adenocarcinomas seropositive and
      seronegative for Helicobacter pylori.
AB  - The preoperative seropositivity of Helicobacter pylori was determined in 128
      patients who had undergone gastrectomy for primary gastric adenocarcinoma during
      the past 5 years. The overall seroprevalence of H. pylori was 64 per cent.
      Gastric cancers positive for H. pylori were associated with tumours located in
      the lower third of the stomach which were of localized type (Borrmann I and II)
      (P < 0.05), but not with age, sex, blood type, tumour size, invasion depth, lymph
      node metastases, histological type, DNA ploidy or type of surgery. The cumulative
      5-year survival curves after surgical resection were significantly better in
      patients who were positive for H. pylori. Multivariate analysis revealed that
      seropositivity for H. pylori was not an independent prognostic factor.
      Pathological tumour node metastasis staging was the only prognostic indicator.
      Better prognosis for those with H. pylori-seropositive gastric cancer may be
      attributed to the more advanced stage of H. pylori-seronegative gastric cancers.
      The potential role of H. pylori in gastric cancer carcinogenesis and its
      biological significance warrant further investigation.

PMID- 7627517
TI  - Regression and progression of Barrett's oesophagus after antireflux surgery.
AB  - The effects of antireflux surgery on Barrett's oesophagus were studied. Fifty-six
      patients (45 men and 11 women of median age 48.5 (range 20-78) years) with
      histologically confirmed Barrett's oesophagus (greater than 3 cm in length) and
      gastro-oesophageal reflux underwent antireflux surgery. Symptoms were noted and
      patients underwent manometry and pH recording before and after operation, and
      annual flexible endoscopy. Fundoplication resulted in a significant improvement
      in lower oesophageal sphincter pressure (median (interquartile range (i.q.r.)) 8
      (5-14) mmHg before operation versus 17 (11-22) mmHg after operation, P < 0.001).
      Twenty-four of the 56 patients had partial or complete regression of Barrett's
      oesophagus (median (i.q.r.) length 8 (3-18) cm before versus 4 (0-10) cm after
      operation, P < 0.001) but nine showed progression (median (i.q.r.) length 6 (3
      11) cm before versus 10 (6-15) cm after operation, P < 0.01) (median follow-up
      5.5 (range 2.0-10.5) years). Carcinoma developed in one patient. The length of
      Barrett's oesophagus was unchanged in 23 patients. Regression was more likely to
      occur in patients who underwent fundoplication with previous or concomitant
      vagotomy (chi 2 = 7.21, 1 d.f., P < 0.01) and in those with a good symptomatic
      result (chi 2 = 23.52, 1 d.f., P < 0.001).

PMID- 7627518
TI  - Use of a feeding jejunostomy after oesophagogastric surgery.
AB  - Over a 5-year period, 58 patients with oesophageal or gastric malignancy
      underwent surgical resection with oesophagogastric or oesophagojejunal
      anastomosis. All were fed temporarily with a catheter feeding jejunostomy placed
      at the time of surgery. All patients tolerated the feeding well. There were no
      catheter-related deaths and only one serious complication, formation of an
      abscess following catheter dislodgement. Experience with this technique suggests
      that it is safe and cheap method of feeding patients after oesophagogastric
      surgery. Such patients are particularly suitable for a feeding jejunostomy as
      they are frequently malnourished, rarely have prolonged postoperative ileus and
      may develop complications that delay the onset of oral intake.

PMID- 7627520
TI  - Segmental arteries to segments I-IV from the common hepatic artery.

PMID- 7627519
TI  - Laparoscopic repair of perforated peptic ulcer.
AB  - A total of 100 consecutive patients with perforated duodenal or juxtapyloric
      ulcers were treated by: laparotomy and omental patch repair (group 1, n = 44);
      laparoscopic suture patch repair (group 2, n = 35); and laparoscopic fibrin glue
      repair (group 3, n = 21). The three groups were comparable in Acute Physiology
      And Chronic Health Evaluation II score and in other known operative risk factors
      such as shock on admission, delayed presentation and associated underlying
      medical illness. Operative mortality and morbidity data were identical in all
      groups. The mean operating time was 52.1, 101.3 and 61.1 min respectively in the
      three groups (group 1 versus group 2, group 2 versus group 3, and group 1 versus
      groups 2 and 3 combined, P < 0.001). The median number of doses of analgesia
      required after operation was 4, 3 and 1 respectively (group 1 versus groups 2 and
      3, P < 0.05). Conversion to laparotomy was necessary in six patients in group 2
      and in one in group 3 (P not significant). The median hospital stay was 5 days in
      all three groups. Patients who underwent laparoscopic repair of perforated peptic
      ulcer required fewer postoperative doses of analgesia than those who had open
      repair. Laparoscopic glue repair has the additional advantage over laparoscopic
      suture of being technically simpler; it also takes less time to perform.

PMID- 7627521
TI  - Purse-string suture applicator and linear resector (EPR 18/70): a new device for
      laparoscopic surgery.

PMID- 7627522
TI  - Diagnostic laparoscopy combined with laparoscopic ultrasonography in staging of
      cancer of the pancreatic head region.
AB  - The aim of this study was to assess the additional role of diagnostic laparoscopy
      combined with laparoscopic ultrasonography in the staging of patients with
      pancreatic head malignancy. Between January 1993 and June 1994, 73 patients with
      stage I cancer of the pancreatic head determined by preoperative investigation
      (endoscopic retrograde cholangiopancreatography and Doppler ultrasonography) were
      eligible for laparoscopic ultrasonography. The peritoneal cavity was investigated
      for peritoneal deposits, intrahepatic metastases, malignant infiltration of the
      portal and superior mesenteric vessels, and N3 lymph node metastases. All
      patients without histologically proven metastases proceeded to laparotomy.
      Seventy patients were eligible for evaluation. Sixteen of the 21 patients with
      distant metastases were diagnosed by laparoscopy with ultrasonography. Forty-nine
      patients had surgical exploration and trial dissection to assess local
      resectability. Twenty-nine patients (41 per cent) had resectable pancreatic head
      tumours. The positive predictive value of local ingrowth as determined by
      laparoscopic sonography was 93 per cent. Laparotomy was avoided in 19 per cent of
      patients and the preoperative stage was changed in 41 per cent. Laparoscopy
      including ultrasonography was effective in staging pancreatic head malignancy.

PMID- 7627524
TI  - Pancreatitis associated with choledochal cyst and other anomalies in childhood.
AB  - Fifty-one children with anatomical anomalies of the pancreatic duct developed
      pancreatitis associated with either congenital dilatation of the bile duct
      (choledochal cyst; n = 48) or other rare causes (n = 3). Among those with
      choledochal cyst, 41 underwent primary surgical resection of the dilated bile
      duct, while five of the remaining seven patients receiving cystenterostomy
      underwent secondary resection of the cyst.

PMID- 7627523
TI  - Clinical improvement after liver transplantation for type I familial amyloid
      polyneuropathy.
AB  - Long-term results of 13 liver transplantations in patients with a previous
      diagnosis of type I familial amyloid polyneuropathy (FAP) are presented. The
      diagnosis of type I FAP was based on the presence of a biochemical marker in the
      plasma (TTR-Met-30 in 11 patients, TTR-Ala-71 in two). Maximum follow-up is 28
      months and the survival rate stands at 11 of 13 patients. Two patients died from
      sepsis at 2 and 6 months. TTR disappeared from plasma in all cases. Neurological
      status improved in all eight patients undergoing transplantation more than 6
      months previously, although electromyographic studies showed a slight improvement
      only in the six with follow-up of more than 1 year. All 13 patients showed a
      hyperdynamic haemodynamic pattern with a high incidence (four patients) of the
      use of venovenous bypass due to haemodynamic intolerance. Two patients also
      received transplants by the 'piggy-back' technique. In conclusion, liver
      transplantation may be useful in the treatment of certain patients with FAP to
      halt and improve the neurological consequences of the disease.

PMID- 7627526
TI  - Total hepatectomy and liver transplantation: a life-saving procedure in patients
      with severe hepatic trauma.
AB  - Management of blunt hepatic trauma has been refined recently and now ranges from
      non-operative measures to the use of extensive surgical techniques. A consecutive
      series of eight patients was treated by total hepatectomy, either with a
      temporary portacaval shunt as a bridging procedure (since no donor liver was
      available immediately; six patients) or followed by standard liver
      transplantation (two). Previous operations included perihepatic packing, deep
      suturing, partial liver resection and hepatic artery ligation, and were attended
      by severe complications, namely uncontrollable bleeding (four patients) and
      massive liver necrosis (four). Six of the eight patients died from multiorgan
      failure or sepsis, and two recipients are alive 49 and 67 months after two-stage
      hepatectomy and transplantation. This experience demonstrates that total
      hepatectomy can be a life-saving procedure in exceptional emergencies in patients
      with potentially lethal hepatic trauma. The prognosis is dependent not only on
      the severity of liver injury but also on the complications of primary treatment.

PMID- 7627525
TI  - Comparison of continuous versus intermittent ischaemia-reperfusion during liver
      resection in an experimental model.
AB  - It has been proposed that regular restoration of blood flow is beneficial during
      liver surgery with vascular isolation. The aim of this study was to compare
      intermittent versus continuous occlusion of blood flow to the resected liver, as
      measured by survival, liver function tests and histological examination. Male
      Wistar rats were allocated to have either sham operation, 80 per cent liver
      resection with 30 min continuous occlusion, or resection with intermittent
      occlusion (two 15-min periods of ischaemia separated by 5 min reperfusion). There
      was no significant difference in the survival rate, with 17 of 20 animals
      surviving in both ischaemia groups. There was a significantly higher serum
      alanine aminotransferase concentration on day 1 in animals receiving continuous
      occlusion, and significantly higher concentrations of bilirubin on days 8 and 23
      and of serum alkaline phosphatase on day 23 in those having intermittent
      ischaemia (P < 0.001). There was a significantly greater loss and slower
      regaining of weight when occlusion was intermittent. Histological changes were
      significantly more pronounced at day 23 in animals undergoing intermittent
      ischaemia (P < 0.05), although these were in only one grading. Continuous and
      intermittent occlusion affected the components of liver function tests
      differently, with no advantage for one technique. These findings suggest that
      periodic release of inflow occlusion during liver surgery is not necessary.

PMID- 7627527
TI  - Octreotide inhibits the growth and development of three types of experimental
      liver metastases.
AB  - A study was performed to assess the effects of octreotide on the growth and
      development of liver metastases in rats. Tumour was induced by intraportal
      injection of three tumorigenic cell lines (the fibrosarcoma HSN and colonic
      adenocarcinomas K12/Tr and WB2054M) in syngeneic rats. Octreotide treatment (2
      micrograms subcutaneously for 3 or 4 weeks) was started 18 h and 1 week after
      tumour induction; a delay in treatment of 1 week allowed micrometastases to
      develop. Treatment with octreotide significantly (P < 0.001) reduced the median
      hepatic replacement of liver by tumour compared with that of control rats given
      saline (controls: HSN 76.4 per cent, K12/Tr 17.5 per cent, WB2054M 43.9 per cent;
      octreotide treatment delayed 18 h: HSN 2.7 per cent, K12/Tr 0.6 per cent, WB2054M
      1.3 per cent; octreotide treatment delayed 1 week: HSN 9.3 per cent, K12/Tr 2.5
      per cent, WB2054M 2.3 per cent). These results clearly indicate that octreotide
      significantly inhibits the growth and development of experimental liver
      metastases. Further studies are required both to delineate the mechanism of
      action and to investigate these effects in a clinical setting.

PMID- 7627528
TI  - Effect of carbon dioxide pneumoperitoneum on bacteraemia and endotoxaemia in an
      animal model of peritonitis.
AB  - Laparoscopy is increasingly used in conditions complicated by peritonitis. A
      theoretical concern is that carbon dioxide pneumoperitoneum may increase
      bacteraemia. This study examines the effect of carbon dioxide pneumoperitoneum on
      bacteraemia, endotoxaemia and physiological correlates of sepsis in an animal
      model of peritonitis. New Zealand white rabbits were assigned to three groups of
      six animals. Group 1 received an intraperitoneal inoculation of 10(9) colony
      forming units of Escherichia coli followed by a 10-cm midline laparotomy. Group 2
      received an identical bacterial inoculum followed by a 12-mmHg carbon dioxide
      pneumoperitoneum for 1 h. Group 3 received no bacteria but had a 12-mmHg carbon
      dioxide pneumoperitoneum for 1 h. Groups 1 and 2 had significantly higher levels
      of bacteraemia (P < 0.01) and endotoxaemia (P < 0.01) accompanied by
      significantly lower mean arterial pressures (P < 0.05) and higher heart rates (P
      < 0.05) compared with group 3. After 6 h groups 1 and 2 were significantly
      hypocarbic (P < 0.01), leucopenic (P < 0.01) and thrombocytopenic (P < 0.01).
      There was no difference between group 1 and group 2. A carbon dioxide
      pneumoperitoneum of 12 mmHg does not increase bacteraemia or endotoxaemia, nor
      does it adversely affect physiological or laboratory correlates of sepsis
      compared with laparotomy in this animal model of peritonitis.

PMID- 7627529
TI  - Comparison of direct vision and electronic two- and three-dimensional display
      systems on surgical task efficiency in endoscopic surgery.
AB  - Task efficiency and knot strength was evaluated under standardized conditions
      using direct vision and electronic imaging with two-dimensional (2-D) and three
      dimensional (3-D) systems. Three operators with different endoscopic surgical
      experience tied a surgeon's knot with standard endoscopic instruments using the
      three different visual systems in random order. Each operator tied 20 knots with
      each visual system. Median task efficiency (defined as the time to complete the
      knot) was 35.0 (interquartile range (i.q.r.) 30.3-43.8) s for direct vision and
      53.0 (i.q.r. 45.3-62.8) s and 53.5 (i.q.r. 45.0-64.8) s for 2-D and 3-D imaging
      respectively (P < 0.05). With respect to direct vision, this represented an
      overall degradation of task efficiency with the use of electronic imaging of 52
      per cent, with no detectable difference between 2-D and 3-D imaging. The knot
      strength, representing the degree of tightening, was weaker with electronic
      imaging but the difference was not significant due largely to variation between
      the three operators.

PMID- 7627530
TI  - Return to work after laparoscopic cholecystectomy.

PMID- 7627531
TI  - Urine testing for acute lower abdominal pain in adults.

PMID- 7627532
TI  - Molecular and cellular basis of cancer invasion and metastasis: implications for
      treatment.

PMID- 7627533
TI  - Delayed diagnosis of malignant tumours missed at laparoscopic cholecystectomy.

PMID- 7627534
TI  - Virtual reality and laparoscopic surgery.

PMID- 7627535
TI  - Inflammatory mediators in acute pancreatitis.

PMID- 7627536
TI  - Duplex ultrasonography for assessment of venous valvular function of the lower
      limb.

PMID- 7627537
TI  - Interstitial laser photocoagulation as a treatment for breast cancer.

PMID- 7627538
TI  - Systemic responses in patients with intermittent claudication after treadmill
      exercise.

PMID- 7627539
TI  - Laparoscopic ultrasonography in the evaluation of the biliary tree during
      laparoscopic cholecystectomy.

PMID- 7627540
TI  - [Pathology of the lymphatic system. Selected problems].

PMID- 7627541
TI  - DNA replication. A familiar ring to DNA polymerase processivity.
AB  - Structural similarity reveals that prokaryotic and eukaryotic DNA polymerases
      share a mechanism for processivity--but the conservation of additional
      chromosomal replication mechanisms remains to be determined.

PMID- 7627543
TI  - Schizophrenia. When neurons go astray.
AB  - Recent prospective studies indicate that schizophrenia manifests itself in
      behavioural abnormalities much earlier than was previously thought, supporting
      the view that schizophrenia is a developmental disorder.

PMID- 7627542
TI  - Muscular dystrophy. Brain, as well as brawn?
AB  - Mutations in the dystrophin gene can lead to muscular dystrophy. The dystrophin
      associated complex of proteins that was first characterized at the muscle cell
      membrane is now also being found in other cell types.

PMID- 7627544
TI  - Head development. Craniofacial genetics makes headway.
AB  - Studies of neural crest migration in animal models, and of human syndromes in
      which craniofacial development is abnormal, are helping us to understand both
      prenatal and postnatal development of the head.

PMID- 7627545
TI  - Lymphocyte development. Intrinsic checkpoints for lineage progression.
AB  - A new T-cell receptor alpha-chain-like molecule has been identified in precursor
      T cells. This protein may be part of a receptor complex that induces T-cell
      maturation.

PMID- 7627546
TI  - Protein folding. An unfolding story.
AB  - A unified and coherent picture for the mechanism of protein folding is emerging.
      The crucial factor in folding is the cooperativity of multiple interactions that
      is required for stability of the folded state.

PMID- 7627547
TI  - Chromosome structure. Coiling up chromosomes.
AB  - The mechanism by which eukaryotic chromosomes condense as cells enter mitosis has
      long been inaccessible to molecular biologists. An important clue has now been
      provided by a ubiquitous protein family, the SMCs.

PMID- 7627548
TI  - Flower development. Origin of the cauliflower.
AB  - A mutant gene that is responsible for generating cauliflower-like heads in the
      model laboratory plant Arabidopsis has been cloned, and the same gene has been
      shown to be mutant in edible cauliflowers.

PMID- 7627549
TI  - HIV integration. Ini1 for integration?
AB  - The newly discovered Ini1 cellular protein binds HIV-1 integrase and is part of a
      protein complex thought to alter nucleosomal structure; such alterations may
      influence the selection of sites for HIV-1 DNA integration.

PMID- 7627550
TI  - Morphogenesis. Cell death returns to its roots.
AB  - Cell-death researchers are looking back at an old question, as interest is
      revived in exploring the role of cell death in morphogenesis.

PMID- 7627551
TI  - Ion-channel gating. Twist to open.
AB  - Three-dimensional images of the open state of the nicotinic acetylcholine
      receptor have been obtained at 9 A resolution. Comparison with the closed state
      reveals the structural basis of channel gating.

PMID- 7627552
TI  - Cell-cycle checkpoints. Keeping mitosis in check.
AB  - Mutations in an essential yeast gene, encoding DNA polymerase epsilon, abolish
      the dependence of mitosis on the completion of DNA replication, suggesting that
      the replication complex provides the checkpoint signal.

PMID- 7627553
TI  - Micromanipulation. Whole-cell manipulation by optical trapping.
AB  - The contact-free, non-invasive manipulation provided by optical trapping enables
      us not only to measure physical parameters of individual cells but also to
      initiate specific responses in a given cell in a defined environment.

PMID- 7627554
TI  - Two different subunits of importin cooperate to recognize nuclear localization
      signals and bind them to the nuclear envelope.
AB  - BACKGROUND: Selective protein import into the cell nucleus occurs in two steps:
      binding to the nuclear envelope, followed by energy-dependent transit through the
      nuclear pore complex. A 60 kD protein, importin, is essential for the first
      nuclear import step, and the small G protein Ran/TC4 is essential for the second.
      We have previously purified the 60kD importin protein (importin 60) as a single
      polypeptide. RESULTS: We have identified importin 90, a 90 kD second subunit that
      dissociates from importin 60 during affinity chromatography on nickel (II)
      nitrolotriacetic acid-Sepharose, a technique that was originally used to purify
      importin 60. Partial amino-acid sequencing of Xenopus importin 90 allowed us to
      clone and sequence its human homologue; the amino-acid sequence of importin 90 is
      strikingly conserved between the two species. We have also identified a
      homologous budding yeast sequence from a database entry. Importin 90 potentiates
      the effects of importin 60 on nuclear protein import, indicating that the
      importin complex is the physiological unit responsible for import. To assess
      whether nuclear localization sequences are recognized by cytosolic receptor
      proteins, a biotin-tagged conjugate of nuclear localization signals linked to
      bovine serum albumin was allowed to form complexes with cytosolic proteins in
      Xenopus egg extracts; the complexes were then retrieved with streptavidin
      agarose. The pattern of bound proteins was surprisingly simple and showed only
      two predominant bands: those of the importin complex. We also expressed the human
      homologue of importin 60, Rch1p, and found that it was able to replace its
      Xenopus counterpart in a functional assay. We discuss the relationship of
      importin 60 and importin 90 to other nuclear import factors. CONCLUSIONS:
      Importin consists of a 60 and a 90 kD subunit. Together, they constitute a
      cytosolic receptor for nuclear localization signals that enables import
      substrates to bind to the nuclear envelope.

PMID- 7627555
TI  - PDGF stimulates an increase in GTP-Rac via activation of phosphoinositide 3
      kinase.
AB  - BACKGROUND: Phosphoinositide 3-kinases (PI 3-kinases) are thought to play an
      important role in coordinating the responses elicited by a variety of growth
      factors, oncogene products and inflammatory stimuli. These responses include
      activation of membrane ruffling, chemotaxis, glucose transport, superoxide
      production, neurite outgrowth and pp70 S6 kinase. Some of these responses are
      also known to be regulated by Rac, a small GTP-binding protein related to Ras.
      Neither the transducing elements upstream of Rac, nor those downstream of PI 3
      kinase, have been defined. RESULTS: We show here that platelet-derived growth
      factor (PDGF) can stimulate an increase in the level of GTP-Rac by at least two
      distinct mechanisms: firstly, by increased guanine nucleotide exchange; and
      secondly, by inhibition of a Rac GTPase activity. The first of these mechanisms
      is essential for the activation of Rac, and we show that it is dependent upon
      PDGR-stimulated synthesis of phosphatidylinositol (3,4,5)-trisphosphate.
      CONCLUSIONS: These results suggest that Rac activation lies downstream of PI 3
      kinase activation on a PDGF-stimulated signalling pathway. Furthermore, as Rac
      has been implicated in at least two diverse cellular responses that are also
      though to require activation of PI 3-kinase--a reorganization of the actin
      cytoskeleton known as membrane ruffling and the neutrophil oxidative burst--these
      results suggest that Rac may be a major effector protein for the PI 3-kinase
      signalling pathway in many cell types.

PMID- 7627556
TI  - Regulation of pre-mRNA processing by src.
AB  - BACKGROUND: Changes in gene expression in response to external signals provide a
      key mechanisms for the regulation of higher eukaryotic cell functions. The
      importance of transcriptional control in the response of cells to growth factors
      and cytokines has been extensively documented, but gene expression has also been
      shown to be controlled at other levels, such as the stability of mRNA in the
      cytoplasm, its localization and translation. By contrast to transcriptional
      control, little is known of the contribution of pre-mRNA nuclear processing to
      the regulation of gene expression, as most of our knowledge of pre-mRNA
      processing in vivo is indirect, being inferred from comparisons of transcription
      rates and levels of mRNA accumulation. RESULTS: In this study, we have used as a
      model the well-characterized maturation pathway of transcripts of the cytokine,
      tumour necrosis factor beta (TNF beta). We have used the murine TNF beta gene as
      a reporter for pre-mRNA processing, using a co-transfection approach to
      investigate whether overproduction of proteins involved in signal transduction
      influences the processing of TNF beta transcripts. Although transfection of both
      activated ras and src genes led to an increase in RNA accumulation in the nuclear
      and cytoplasmic compartments, as expected from their transactivation of the TNF
      beta expression vector, only src induced a modification of RNA processing.
      Comparison of several modes of src activation indicated that two distinct effects
      of src on pre-mRNA processing can be coupled: one involves slowing down splicing
      and the other allows the export of partially spliced transcripts. These effects
      can be observed not only on the three introns of TNF beta but also on transcripts
      from a beta globin expression vector. DISCUSSION: We have characterized how the
      processing of transcripts of TNF beta and beta globin is regulated by the signal
      transduction pathway that includes the Src protein, establishing that external
      signals have the capacity to regulate gene expression at a post-transcriptional
      level within the nucleus. Src seems to act on a general mechanism of splicing
      and/or mRNA transport, but its biologically relevant targets are likely to be
      restricted to genes for which either alternative processing pathways are in
      competition, or the kinetics of splicing is critical. This regulation could
      reflect a modulation by Src of the activity of components of the splicing and
      transport machineries, but could also involve RNA-binding proteins, which have
      been shown to interact with Src.

PMID- 7627557
TI  - Elevated levels of wild-type p53 induced by radiolabeling of cells leads to
      apoptosis or sustained growth arrest.
AB  - BACKGROUND: The tumor suppressor protein p53 regulates progression through the
      checkpoint between the G1 and S phases of the cell cycle in response to radiation
      or drug-induced DNA damage. We have examined potential p53-mediated effects of
      metabolically labeling cultured mammalian cells with [35S]methionine and
      [3H]thymidine, methods that are commonly used to study the biochemical
      properties, synthesis, processing and degradation of proteins and the replication
      of DNA in proliferating cells. RESULTS: Wild-type p53 protein concentrations
      rapidly increased to high levels following metabolic radiolabeling of cells, as
      determined by four distinct assays. The increased concentration of wild-type p53
      resulted in apoptosis of normal human peripheral blood lymphocytes and of murine
      T-cell acute lymphoblastic leukemia cells. In leukemia cells containing no p53,
      or only mutant p53 alleles, p53 protein levels were not increased and the cells
      did not undergo apoptosis in response to radioactive labeling. Radiolabeling of
      human diploid fibroblasts resulted in a prolonged growth arrest that was
      maintained for nearly three weeks. CONCLUSIONS: The results of experiments
      employing radiolabeling techniques to characterize various aspects of cellular
      physiology may be seriously influenced by the induction of aberrant cell-cycle
      arrest and/or apoptosis mediated by wild-type p53. Furthermore, our observations
      suggest that stabilization of wild-type p53 in response to irradiation may not
      act primarily to facilitate the repair of DNA damage by inducing a transient G1
      phase arrest, but rather to ensure genetic stability through sustained cell-cycle
      arrest or apoptotic death of the damaged cells.

PMID- 7627558
TI  - Quantitative effects of hedgehog and decapentaplegic activity on the patterning
      of the Drosophila wing.
AB  - BACKGROUND: Members of the hedgehog (hh) gene family encode a novel class of
      proteins implicated in positional signalling in both invertebrates and
      vertebrates. In Drosophila, the hh gene has been shown to regulate patterning of
      the imaginal discs, the precursors of the insect limbs. In a remarkably similar
      fashion, the function and expression of the sonic hedgehog (shh) gene is closely
      associated with the 'zone of polarizing activity' (ZPA) that controls antero
      posterior patterning of the vertebrate limb. Both of these functions suggest a
      role for hedgehog family proteins as morphogens. An alternative possibility,
      however, is that hh and its homologues act to control the expression of other
      instructive signalling molecules. RESULTS: We have explored this issue by
      examining the effects on Drosophila wing patterning of ectopically expressing
      varying levels of hh and shh, as well as of the putative hh target gene,
      decapentaplegic (dpp), a member of the transforming growth factor-beta family of
      signalling molecules. We find that different levels of hh activity can induce
      graded changes in the patterning of the wing, and that zebrafish shh acts in a
      similar though attenuated fashion. Varying levels of ectopic hh and shh activity
      can differentially activate transcription of the patched and dpp genes.
      Furthermore, ectopic expression of dpp alone is sufficient to induce the pattern
      alterations caused by ectopic hh or shh activity. CONCLUSION: Thus, hh family
      proteins can elicit different responses in a dose-dependent manner in the
      imaginal disc. The principal function of hh, however, is to activate
      transcription of dpp at the compartment boundary, thereby establishing a source
      of dpp activity that is the primary determinant of antero-posterior patterning.

PMID- 7627559
TI  - Regulation of Caenorhabditis elegans degenerin proteins by a putative
      extracellular domain.
AB  - BACKGROUND: Rare, dominant mutations in the degenerin genes of Caenorhabditis
      elegans (deg-1, mec-4 and mec-10) cause neuronal degeneration. The extensive
      sequence similarity between degenerins and mammalian genes that encode subunits
      of the amiloride-sensitive sodium channel from kidney, colon and lung suggests
      that the C. elegans degenerins form ion channels. As mec-4 and mec-10 are needed
      for the reception of gentle touch stimuli, they may contribute to a
      mechanosensory ion channel. All the dominant degeneration-causing mutations in
      the C. elegans degenerin genes affect equivalent residues in a hydrophobic region
      that is structurally similar to the H5 domain of several ion channels, and so
      could form the channel lining. Increased channel activity may underlie the
      resulting degeneration, in which the affected cells vacuolate and swell. RESULTS:
      We now demonstrate that a missense change in a predicted extracellular region of
      the proteins encoded by deg-1 and mec-4 causes cell death similar to that caused
      by the dominant mutations. The missense mutation lies within a 22 amino-acid
      region found in all the C. elegans degenerins for which the sequences have been
      published, but not in the similar mammalian proteins. Deletion of nine amino
      acids surrounding the mutation site in mec-4 also causes neuronal degeneration.
      The degeneration-causing mutations in either the predicted pore-lining or the
      predicted extracellular regions of deg-1 are suppressed by additional, dominantly
      acting mutations that substitute larger for smaller residues within the channel
      lining. CONCLUSIONS: Our data suggest that the putative extracellular domain
      negatively regulates degenerin activity, perhaps by gating the channel. As this
      region is only found in the C. elegans proteins, it may allow more rapid
      regulation of the nematode channels, which may be needed for them to function in
      mechanosensation. The suppressor mutations, by adding larger amino acids to the
      putative pore lining, could prevent degeneration by blocking the pore of a
      multisubunit channel.

PMID- 7627560
TI  - [Will prevention be better than cure for allergies and asthma in the 1st 20 years
      of the next century?].

PMID- 7627561
TI  - [Skin tests in allergy].
AB  - Allergen skin testing is one of the preferred in vivo methods for assessing the
      presence of specific IgE antibodies against an allergen. This article review the
      clinical applications, techniques, reagents, evaluation, and safety of skin
      testing to help the allergologist to its better clinical use.

PMID- 7627562
TI  - [Applications and goals of molecular biology].
AB  - Clonal studies define the proteic sequence of several allergens leading to the
      recombination and the use of them for immunotherapy extracts. It has been
      possible to clone the receptors for IgE in basophils and mast cells and the
      regulation mechanisms had been delucidates. In a near future it will be possible
      to design recombinant molecules for the specific inhibition of synthesis and
      receptors of IgE and avoid the signal transmissions and the release of mediators.
      The diagnosis of several diseases is based in molecular techniques, inclusive in
      uterus. Genes for various diseases had been cloned in immunology, recombinations
      with gamma interferon had been used for treatment of subjects with atopic
      dermatitis and chronic granulomatous disease.

PMID- 7627564
TI  - Seizure-protecting effects of kyotorphin and related peptides in an animal model
      of epilepsy.
AB  - Administration of peptides kyotorphin (KT), neokyotorphin (NKT), and d-ser-2-NKT
      into the lateral brain ventricle (10 nmol) increased the latency and attenuated
      the severity of picrotoxin-induced convulsions in rats. Anticonvulsive effects of
      the peptides were also observed after their administration into the CA1
      hippocampi (2.5, 5, 10 nmol), with the order of potency d-ser-2-NKT-->NKT-->KT.
      When injected into the substantia nigra reticulata, the 10 nmol dose of NKT and d
      ser-2-NKT displayed equal seizure-protecting effect, which was higher than that
      for KT. It is concluded that kyotorphin and its analogs provide structure
      dependent, dose-dependent, and target site-dependent antiepileptic effect.

PMID- 7627563
TI  - [Comparative study of plethysmography and spirometry in asthmatic children].
AB  - The aim of the study was to evaluate the results of plethysmography in comparison
      to spirometry. A retrospective study of pulmonary function tests was performed in
      50 asthmatic children, 6 to 15 years old, free of acute symptoms. Mild airway
      obstruction was found in 8 spirometries, while the other 42 were found within
      normal limits. In the plethysmography, obstruction was found in 27 cases, 23
      without abnormalities in resistance or specific conductance. Eleven cases
      suggested pulmonary air trapping and/or hyperinflation. Airway obstruction was
      evident in 54% of plethysmographies. The difference between both studies was
      significant, also as well as the airway obstruction and intensity of the clinical
      disease. We therefore conclude that the plethysmography shows more alteration in
      their parameters than spirometry for the detection or suggestion of airway
      obstruction in asthmatic children during asymptomatic periods.

PMID- 7627565
TI  - Responses of extrahypothalamic neurons to short temperature transients during the
      ultradian wake-sleep cycle.
AB  - The thermosensitivity of neurons in thalamo-striate-limbic structures located
      dorsally to the classical thermosensitive anterior hypothalamic-preoptic region
      was studied in cats during the natural ultradian wake-sleep cycle. Direct cooling
      or warming of the brain tissue by means of water-perfused thermodes was combined
      with tonic cooling or warming of the abdominal wall using a water-perfused heat
      exchanger on which the animal was lying. Out of 482 neurons, 116 (24.1%) were
      thermosensitive. They were located in the nuclei reticularis and ventralis
      anterior of the thalamus, the fundus of the caudate nucleus, the bed nucleus of
      the stria terminalis, the bed nucleus of the inferior thalamic peduncle, and the
      nucleus of the anterior commissure. Abdominal warming increased the effect of
      direct brain warming and decreased the effect of direct brain cooling; opposite
      effects were obtained by abdominal cooling. Thermosensitivity was present during
      wakefulness and synchronized sleep, but depressed or altered during
      desynchronized sleep.

PMID- 7627566
TI  - Anorexic action of a new potential neuropeptide Y antagonist [D-Tyr27,36, D
      Thr32]-NPY (27-36) infused into the hypothalamus of the rat.
AB  - Neuropeptide Y (NPY) produces a vigorous feeding response in several species when
      it is injected into hypothalamic structures involved in eating behavior. The
      purpose of this study was to determine whether a unique carboxy terminal fragment
      of NPY would alter the pattern of eating induced in the rat either by NPY
      injected into the hypothalamus or by a 24-h period of food deprivation. In this
      case, two L-tyrosine residues and one L-threonine residue of the NPY27-36
      fragment were transformed to their D-conformation to produce [D-Tyr27,36,D-Thr32]
      NPY (27-36), i.e., D-NPY27-36. Guide cannulae for microinjection were implanted
      stereotaxically just dorsal to the paraventricular nucleus (PVN) or ventromedial
      hypothalamus (VMH) of 24 adult male Sprague-Dawley rats. Following postoperative
      recovery, a microinjection of artificial CSF or 1.1 microgram or 3.3 micrograms
      of a peptide was made directly into the PVN or VMH as follows: native NPY; D
      NPY27-36; or [L-Tyr27,36, L-Thr32]-NPY (27-36), i.e., L-NPY27-36. Food intakes
      were measured at intervals of 0.25, 0.5, 1.1, 2.0, 4.0, and 24 h. When D-NPY27-36
      was microinjected at NPY reactive sites in the PVN or VMH of the rat 15 min
      before a similar microinjection of NPY, the intense eating response induced by
      the peptide was reduced significantly. Not only was the effect dose dependent,
      but D-NPY27-36 also augmented the latency to feed. A mixture of the two doses of
      NPY and D-NPY27-36 injected at the same hypothalamic loci did not attenuate the
      intake of food but tended to enhance the feeding response in the rats.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7627568
TI  - Auditory input to the pedunculopontine nucleus: I. Evoked potentials.
AB  - The pedunculopontine nucleus (PPN) has been implicated in sleep-wake control,
      arousal responses, and motor functions. The PPN also has been implicated in the
      generation of the P1 middle-latency auditory-evoked potential. The present study
      was undertaken to determine the topographical distribution, threshold, and
      response properties of depth-recorded potentials following auditory click
      stimulation. Experiments were conducted in both decerebrate cat and rat, with a
      view towards determining the presence of P1-like middle-latency auditory-evoked
      potentials in the midbrain of both species. These results demonstrate a) the
      presence in and around the PPN of a P1-like potential in the decerebrate rat
      similar to that described in the accompanying article as the P13 in the intact
      rat; b) the presence in and around the PPN of a P1-like potential in the
      decerebrate cat similar to that previously described by others as wave A in the
      intact cat; c) although thresholds for these potentials were similar to those of
      intact preparations, following frequencies were higher in the decerebrate
      preparations, i.e., responsiveness to repetitive stimulation was higher; and d)
      depth-recorded somatosensory-evoked potentials also were studied in the cat and
      found to show an evoked potential at a similar latency as middle-latency auditory
      depth-recorded potentials. These findings suggest that click stimulus-evoked,
      depth-recorded potentials are present in and around the PPN in the decerebrate
      rat and cat, i.e., in the absence of cortex, at a similar latency as in intact
      preparations.

PMID- 7627569
TI  - Auditory input to the pedunculopontine nucleus: II. Unit responses.
AB  - The pedunculopontine nucleus (PPN) has been implicated in sleep-wake control,
      arousal responses, and motor functions. The PPN also has been implicated in the
      generation of the P1 middle-latency auditory-evoked potential. The present study
      was undertaken to determine the nature of the responsiveness of single neurons in
      and around the PPN following auditory stimulation. Somatosensory responsiveness
      also was tested in some cells. These results demonstrate a) the presence of a
      significant proportion of PPN neurons that respond to auditory click stimuli; b)
      two populations of neurons showing either low threshold/short latency/low
      habituation or high threshold/longer latency/high habituation; c) the responses
      of longer latency neurons precede the onset and peak of depth- and vertex
      recorded middle-latency auditory-evoked potentials; d) thresholds of longer
      latency neurons similar to the threshold for wave A in the intact cat, the P13
      potential in the intact rat, or the startle reflex; and e) convergent
      somatosensory and auditory responses at a similar latency in a number of PPN
      neurons. These findings suggest that neurons in and around the PPN may
      participate in auditory and somatosensory information processing related to
      arousal, and may contribute to the manifestation of the P1 auditory middle
      latency evoked potential.

PMID- 7627567
TI  - A middle-latency auditory-evoked potential in the rat.
AB  - Previous studies have established the presence of a middle-latency auditory
      evoked potential that is characterized by a) sleep-state dependence, b) low
      following frequency (i.e., rapid habituation to repetitive stimulation), and c)
      blockade by the cholinergic antagonist, scopolamine. A vertex-recorded evoked
      potential having these characteristics was described in humans at a 50-80 ms
      latency (termed the P1 or.P50 potential) and in the cat at a 20-25 ms latency
      (termed wave A). These studies were undertaken to determine if a click stimulus
      evoked potential having the same characteristics was present in the intact rat.
      Vertex and auditory cortex recordings in intact rats studied in a sound
      attenuating chamber and exposed to free-field click stimuli showed a) the
      presence of a vertex recorded potential at a 11-15 ms latency, termed P13, and of
      an auditory cortex recorded potential at a 7-11 ms latency, termed Pa; b) the P13
      was present during waking and paradoxical sleep but absent in slow-wave sleep,
      while Pa was present in all sleep-wake states; c) the P13 habituated markedly at
      stimulation rates above 1 Hz while Pa did not; and d) the P13 was blocked by low
      doses of scopolamine while Pa was not. These studies demonstrate the presence of
      a P1-like potential in the rat at a 13 +/- 2 ms latency.

PMID- 7627570
TI  - Localization of tissue plasminogen activator mRNA in adult rat brain.
AB  - The distribution of tissue plasminogen activator (tPA) messenger RNA in rat brain
      was studied using in situ hybridization with 35S UTP-labeled RNA probes derived
      from a full-length tPA cDNA. Sense strand controls produced low, even
      backgrounds, with small elevations in the hippocampus. Full-length antisense
      probes produced strong signals over cerebral ventricular ependyma (including
      ependyma of the subcommissural organ), meninges, blood vessels, and Purkinje cell
      layer of the cerebellum, as well as strong signals over scattered cells
      throughout the brain. Some of these scattered labeled cells were large with
      lightly stained nuclei, while others were small with darkly stained nuclei. The
      large labeled cells, which were probably neurons, constituted 6% and 8% of cells
      in the brain stem and neocortex, respectively, and 100% of Purkinje cells. The
      small cells, which were present in all areas of the brain, constituted 3-11% of
      cells in individual brain areas.

PMID- 7627571
TI  - Lateral geniculate neuron responses to drifting sine-wave gratings in rabbits.
AB  - Neurons of the lateral geniculate body in rabbits were excited with drifting sine
      wave gratings. Rabbits were anesthetized and paralyzed under conventional methods
      to record action potentials of single cells using tungsten in glass
      microelectrodes. All classes of geniculate cells responded in a modulatory
      pattern. It appears that the unmodulatory pattern typical of complex cell types
      of the cortex is extremely infrequent or absent. In the spatial domain most cells
      are low pass and bandpass. Only one unit was high pass. In the temporal domain
      low-pass and bandpass cells were the most frequently recorded. Four geniculate
      cells were high pass. It appears, therefore, that neurons of rabbits' geniculate
      are tuned over spatial and temporal frequencies of sine-wave gratings. The
      comparison with cortical recordings revealed that geniculate cells are more
      broadly tuned than cortical neurons. This study suggests that the rabbit's visual
      system is sensitive to gratings. However cells respond optimally to lower values,
      e.g., broader gratings, than neurons of frontalized eye animals.

PMID- 7627574
TI  - The ingestion of calcium in multiparous and virgin female rats.
AB  - The present experiments demonstrate that multiparous females ingest more calcium
      that virgin females. In two experiments, we demonstrated that multiparous females
      ingested more calcium than virgin females, and both ingested larger amounts than
      males. The biological basis for this enhanced avidity for calcium lie in the
      greater needs for calcium during reproduction.

PMID- 7627573
TI  - L-DOPA metabolism in cortical and striatal tissues in an animal model of
      parkinsonism.
AB  - Rats with unilateral 6-hydroxydopamine lesions of the midbrain tegmentum were
      treated with 25 mg/kg L-DOPA methyl ester/2 mg/kg carbidopa. The effects of the L
      DOPA treatment upon serum, neocortical, and striatal L-DOPA and 3-O-methyl dopa
      (3-OMD) concentrations were measured. The highest L-DOPA and 3-OMD concentrations
      were obtained in the serum and in a ratio of approximately 2:1. In the brain,
      there was a uniform distribution of 3-OMD but L-DOPA concentrations were highly
      nonhomogeneous. Regression line equations for the statistically significant
      correlation coefficients between L-DOPA and tissue dopamine concentrations
      suggested that L-DOPA generated 50-60 times as much dopamine in the intact
      striatum as in cortex. The regional variation of L-DOPA concentration appears
      related to the capability of the brain tissue to generate and store dopamine from
      L-DOPA. In addition, the findings suggest that the behavioral ineffectiveness of
      L-DOPA in intact animals is related to its capacity to transform L-DOPA to tissue
      bound dopamine.

PMID- 7627572
TI  - Cardiovascular effects of NMDA in the RVLM of spontaneously hypertensive rats.
AB  - In this study we found that cardiovascular effects were differentially regulated
      by N-methyl-D-aspartate (NMDA) in the rostral ventral lateral medulla (RVLM) of
      spontaneously hypertensive rats (SHRs) compared to their normotensive controls
      (Wistar-Kyoto rats, WKYs). Adult SHRs and WKYs were anesthetized with urethane,
      cervically vagotomized, and placed in a sterotaxic frame. We found that
      electrical stimulation or local application of N-methyl-D-aspartate into the RVLM
      produced hypertension in both strains. Microinjection (3.5-4.0 nmol) of AP5 (2
      amino-5-phosphono-valerate), an NMDA receptor antagonist, to the RVLM did not
      affect resting blood pressure; however, this agent antagonized hypertensive
      responses evoked by low-frequency electrical stimulation (5-20 Hz) in both
      strains. The elevation in blood pressure evoked by stimulation at a higher
      frequency (60 Hz) was not affected by AP5. These results suggest that NMDA
      receptors are involved in the low frequency, electrically evoked hypertension in
      both strains. We also found that SHRs had a larger pressor response to
      microinjection of NMDA and electrical stimulation than did WKYs. AP5 abolished
      the differences in evoked hypertension between WKYs and SHRs during low-frequency
      (5-10 Hz) electrical stimulation. These data suggest that the hypersensitivity of
      RVLM to low-frequency electrical stimulation in SHRs involve NMDA receptors. We
      previously reported that AP7 antagonizes NMDA and carotid clamping-induced
      hypertension. In this study, we found that when locally applied to RVLM, AP5
      antagonized hypertension evoked by clamping the carotid arteries in SHRs and
      WKYs. Thus, carotid clamping-induced hypertension may also involve NMDA receptors
      in the RVLM.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7627575
TI  - Ascorbic acid concentration in the lateral hypothalamus is related to plasma
      osmolality.
AB  - Microdialysis was used to measure extracellular ascorbic and uric acid
      concentrations in the lateral hypothalamus of water-restricted rats as they drank
      distilled water or 1.5% NaCl. Other water-restricted rats, not implanted with
      microdialysis probes, were decapitated 2 h after beginning to drink these fluids.
      Rats were inverted and their blood was collected for measurements of plasma
      osmolality and percent hematocrit. Results showed that drinking distilled water
      produced a significant increase in the ascorbic acid concentration but not in the
      uric acid concentration. Drinking 1.5% NaCl produced a significant decrease in
      the uric acid concentration but not in the ascorbic acid concentration. Drinking
      distilled water decreased mean osmolality from 306.0 to 291.5 mOsm/kg, whereas
      drinking 1.5% NaCl maintained mean osmolality at water-restricted levels. These
      results indicate that the extracellular fluid concentration of ascorbic acid in
      the lateral hypothalamus rises in response to a fall in plasma osmolality.

PMID- 7627576
TI  - Anticonvulsant effects of memantine and MK-801 in guinea pig hippocampal slices.
AB  - The anticonvulsant properties of memantine (Mem) were compared to those of MK
      801. Extracellular field recordings were obtained from area CA1 of guinea pig
      hippocampal slices in a total submersion chamber at 32 degrees C in normal
      oxygenated artificial cerebrospinal fluid (ACSF). Evoked responses were elicited
      by 0.07 Hz stimulation of the Schaffer collateral and commissural fibers. Bath
      perfusion of slices with Mg(2+)-free ACSF and N-methyl-D-aspartate (NMDA)
      containing ACSF induced epileptiform afterdischarges following evoked responses.
      Pretreatment of slices by bath application of 100 microM Mem for 18-20 min
      prevented epileptiform afterdischarges under both convulsant conditions.
      Perfusion with 100 microM Mem alone for up to 50 min had no discernible effect on
      evoked responses. MK-801 was as effective at < or = 10 microM and required
      application for over 15 min to suppress afterdischarges completely. Both Mem and
      MK-801 suppressed epileptiform activity when applied after such activity was
      induced by NMDA or MG(2+)-free ACSF. The EC50 of Mem was 16.6 microM and that of
      MK-801 was 0.19 microM for blocking NMDA-induced evoked response suppression.
      Thus, in the guinea pig hippocampal slice preparation, Mem appeared to have
      anticonvulsant properties qualitatively similar to those of MK-801, but was 10
      100 fold less potent.

PMID- 7627578
TI  - The spectrum of intracranial aneurysms in pediatrics.
AB  - Intracranial aneurysms are rare in children, accounting for merely 0.5-4.6% of
      all aneurysms. Several characteristics distinguish them from aneurysms in adults:
      male predominance; higher incidence of unusual location, such as peripheral or
      posterior circulation; and a greater number of large and giant aneurysms. These
      unique features can be attributed to the higher incidence of traumatic,
      infectious, developmental, and congenital lesions. Subarachnoid hemorrhage is not
      the exclusive mode of presentation; neuro-compressive signs and symptoms are also
      frequently seen. The treatment of intracranial aneurysms in pediatrics is
      dictated by their unusual pathology and liability to rehemorrhage. Although
      direct clipping has been the standard surgical technique, certain obsolete or
      innovative procedures should also be considered, such as entrapment, proximal
      occlusion, and endovascular embolisation, or even, in some cases, the non
      invasive treatment of "watch and wait" for a spontaneous thrombosis. Six
      representative cases from King Faisal Specialist Hospital and Research Centre are
      reviewed. They reflect the diversity of the problem and the multi-disciplinary
      approach to the treatment.

PMID- 7627577
TI  - A method for labeling embryonic rat medial septal region projection neurons, in
      vitro, using fluorescent tracers.
AB  - A retrograde labeling method is described in which rat embryonic (E18, E21) and
      postnatal (P1) medial septal neurons were labeled with succinyl wheat germ
      agglutin-fluorescein, fluorescent green microspheres, or 1,1'-dioctadecyl
      3,3,3',3'-tetramethyl-indocarbocyanine perchlorate (Dil) following in vitro
      hippocampal injections. The brains were removed and immediately immersed in
      oxygenated Tyrode solution. Dye was pressure injected into the hippocampus
      bilaterally. After incubating the brain in oxygenated Tyrode, the medial septal
      region was removed. The neurons were dissociated and cultured at medium density
      in 35 mm dishes with a hole in the bottom covered by a coverslip with a grid. The
      neurons were observed with a low light system, and cell counts were made at 5,
      24, and 48 h. Labeled and unlabeled neurons showed considerable neurite outgrowth
      and acetylcholinesterase activity in culture. Highly reproducible labeling was
      obtained, with Dil giving the best results. Dil labeled the neurons in vitro, was
      retained during culture for 1 week, and was compatible with cell survival.

PMID- 7627579
TI  - Stereotactic guided microsurgery of cerebral lesions.
AB  - A total of 33 patients presenting with various cerebral lesions were operated on
      with stereotactic guided craniotomy. In all cases the lesion could be totally
      removed and only one patient suffered from a recurrent metastasis. The survival
      time of patients with malignant brain tumors was in the range of the generally
      reported data. All the six patients with malignant gliomas developed a
      recurrence, four of them have since died. Three of the four patients with brain
      metastases died from systemic progression of their disease, and one patient died
      from a recurrence of a centrally located metastasis. A new neurological deficit
      occurred in only two patients. Despite the often deep or central localization of
      the lesions, major complications were rare. Stereotactic guidance and
      preoperative selection of the entry point allow a safer surgical procedure, a
      larger indication for open surgery in cases considered as not removable, and
      reduce surgical morbidity.

PMID- 7627580
TI  - Why did we not see the light? A retrospective analysis of ideas in neurosurgery.
AB  - Based on personal experience, a retrospective analysis of the changes in
      neurosurgical thinking during the past 50 years is presented. The four phases of
      the organisational pattern are discussed. The contributions of a few pioneer
      neurosurgeons are emphasized. The impact of revolutionary technical improvements
      on future neurosurgeons should be balanced by sound clinical judgement--as
      "novelty is not equal to creativity."

PMID- 7627581
TI  - The transoral transpalatal approach to the pituitary fossa.
AB  - Transpalatal trans-sphenoidal approaches to the sella turcica were described as
      early as 1900. Since the advent of effective trans-sphenoidal pituitary
      microsurgery in the 1960's, the sublabial transnasal approach became the most
      widely used. We reassessed the transoral transpalatal approach in 1978 and found
      the procedure to have distinct advantages over the transnasal operation. Between
      1978 and 1992, 94 patients had transpalatal trans-sphenoidal explorations of the
      pituitary fossa at our institution. The detail of the operative technique, the
      results and the advantages are discussed.

PMID- 7627582
TI  - Intraoperative monitoring of median nerve somatosensory evoked potentials in
      cervical syringomyelia: analysis of 28 cases.
AB  - Intraoperative median nerve somatosensory evoked potentials (SEP) were monitored
      in 28 patients undergoing surgery for cervical or cervicothoracic syringomyelia.
      Analysis was focused on SEP components N13 (spinal cord), P14 (brain stem), and
      N20 (cortex). N13 was lacking in nearly 87% of the patients (due to a combined
      effect of syringomyelia and general anesthesia) and never recovered. P14 showed a
      significant (> 10%) intraoperative latency increase in two patients; this was
      irreversible in one patient who had a postoperative worsening of sensory
      function. N20 showed no relevant alterations. Pure motor deficits after surgery
      were not predicted by SEP monitoring. In conclusion, intraoperative P14 recording
      helped to identify harm to the dorsal columns and probably prevented the cord
      from irreversible damage in one case, whereas N13 recording did not contribute to
      the monitoring of spinal cord function during surgery for syringomyelia.

PMID- 7627583
TI  - How angioarchitecture of cerebral arteriovenous malformations should influence
      the therapeutic considerations.
AB  - PURPOSE: To evaluate the angioarchitectural criteria of complex cerebral
      arteriovenous malformations (AVMs), concerning the risk of hemorrhage and therapy
      planing. METHODS: The magnetic resonance (MR) imaging and neuroangiographic
      findings of 227 AVMs (223 patients) were retrospectively evaluated. Statistical
      analysis was used to define the relative frequency of these lesions for
      hemorrhage in correlation with various parameters (i.e. age of the patient, size,
      location, associated aneurysms). RESULTS: Onset of symptoms was between 21 and 40
      years of age in 50% of cases. The ratio of centrally to convexially located
      lesions was 1:2. Convexial AVMs are classified by MR imaging into sulcal and
      gyral, according to the arterial supply (by terminal or transit feeding arteries,
      respectively), as proven by super-selective neuroangiography. Central location of
      the AVM, size of the nidus smaller than 2 cm diameter, and presence of related
      aneurysms, are high risk factors for hemorrhage. AVMs with one or two draining
      enlarged veins, or those without reflux presented a higher incidence of
      hemorrhage as well. CONCLUSION: A team approach is required for the choice of the
      therapeutic method in patients with AVMs. Our results allow an approximate
      prognosis concerning the risk of hemorrhage in these patients and should be taken
      in consideration for the precise therapeutic planing.

PMID- 7627584
TI  - Stereotactic cysto-ventricular shunting in diencephalic (arachnoid) cysts and
      failure in cystic craniopharyngeoma.
AB  - Stereotactic cysto-ventricular shunting in three patients with congenital
      (subependymal cyst of the 3rd ventricle, subependymal cyst of the foramen of
      Monro, cyst of cavum septi pellucidi) and in a female patient with a large cystic
      suprasellar craniopharyngeoma is dealt with in this paper. The first operation
      was performed in May 1992 and the latest, being considered in this paper, in
      October 1993. All patients were admitted to our hospital suffering from signs of
      increased intracranial pressure. CT-scans revealed on the one hand an obstructive
      hydrocephalus subjected to the cystic arachnoid lesions, on the other hand a
      large hypodense suprasellar cystic tumor. After stereotactic puncture of the
      arachnoid cysts, aspiration of their contents as well as biopsy of the wall, a
      silicone catheter was implanted, thus constructing a permanent communication
      between the cyst and the lateral or third ventricle. The internal catheter was
      connected to a subcutaneous burr-hole reservoir. All these patients recovered
      uneventfully without neurological deficits. There were no operative
      complications. Follow-up CT-scans showed no recurrences of the cysts and
      obstructive hydrocephalus. In the patient with the suprasellar craniopharyngeoma
      at first a stereotactic puncture of the cyst was performed. After recurrence the
      tumor was directly approached by an frontotemporal craniotomy. The histological
      examination revealed now a craniopharyngeoma. After renewed recurrence a
      stereotactic cysto-ventriculostomy with internal shunt implantation was
      performed. However, in this case this method was unsuccessful, documented by
      follow-up CT-scans. Resulting from our experiences, it is quite obvious that the
      stereotactic internal shunt implantation seems to be a safe, proper and reliable
      method in the treatment of arachnoid cystic lesions.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7627585
TI  - Reactive attachment disorder in children.

PMID- 7627586
TI  - Family centered care: a theory practice dilemma.

PMID- 7627587
TI  - Enteral feeding in community settings.

PMID- 7627588
TI  - Urine collection from infants: a reliable method.

PMID- 7627589
TI  - Childhood leukaemia.

PMID- 7627590
TI  - Tribute to the pioneer who gave parents a choice.

PMID- 7627591
TI  - Contact a family.

PMID- 7627592
TI  - Contact a family: a parent's story.

PMID- 7627594
TI  - Managing care: multiple accountability.

PMID- 7627593
TI  - Clinical tools for success in managing care.
AB  - Managing care effectively requires a coalition of services that are sensitive to
      individual needs, promote effective resource use, support physician practice, and
      ensure coordination of services across the continuum. Several clinical tools
      exist to establish structures, systems, and processes that integrate management
      of expected and unexpected patient and family needs across the life span and
      throughout the health care continuum. System evaluation; unrelenting
      communication; continuous improvement; case management; empowerment; standards
      based clinical practice; and satisfaction of the patient, family, and care
      provider are some of the tools available to develop systems that effectively
      manage health and illness. This article provides some examples of several of
      these "tools," the process of development and implementation, and evaluation
      strategies.

PMID- 7627595
TI  - Primary nurse accountability for patient care outcomes: taking the first steps.

PMID- 7627596
TI  - Cost-accounting systems.

PMID- 7627597
TI  - Measure performance for a greater sense of accountability.

PMID- 7627598
TI  - Mapping change in health care: pathways for nursing.
AB  - Health care is changing. Economic, political, social, environmental, and cultural
      factors all influence the population's need for health care and the delivery of
      health services. Emphasis is placed on providing quality services at the lowest
      possible costs, leading to a variety of alternatives to hospital care. This
      changing health care scene presents both opportunity and challenge for the health
      care professional. Nursing, in particular, is in a unique position and can play a
      pivotal role in all health care reform initiatives.

PMID- 7627599
TI  - Nurses in ambulatory care: multiple roles and opportunities. Interview by Susan
      Cummings.
AB  - This article presents an interview with a dynamic health care professional who
      has extensive experience in providing nursing care in ambulatory care settings.
      Crabtree's candid and timely responses add to the pursuit of the answers to the
      question that is the title of this issue: "Managing Care: Who's Accountable?"

PMID- 7627600
TI  - A public-private partnership facilitates accountability and outcomes. Interview
      by Susan H. Cummings.
AB  - The article presents an interview about a unique and successful public-private
      partnership that uses social and medical case management services to manage the
      health and social needs of an indigent population. This program, which won the
      Merck/National Managed Health Care Congress Partnership Award in 1993, has
      resulted in client satisfaction, quality care, and cost-effective outcomes.

PMID- 7627601
TI  - Who is the advanced practice nurse?
AB  - Challenges and opportunities for Advanced Practice Nurses are explored during the
      paradigm shift in health care. Role development is presented from a historical
      perspective, and current role activities are discussed related to
      accountabilities for care management. Advanced Practice Nurses with practitioner
      skills of care management coupled with a nursing framework for practice can
      deliver cost-effective primary care in a variety of settings.

PMID- 7627602
TI  - Managing in the next decade: a new set of skills for nurse managers.
AB  - The transition from traditional management to patient-focused leadership
      challenged Lakeland Regional Medical Center nurse managers to re-examine the
      usefulness of many traditional management skills. Patient-focused restructuring
      has changed the role of a traditional Nurse Manager to a leader/coach of our
      empowered staff. Managers now maintain responsibility for managing multiple
      disciplines, self-directed work teams, and redeployed services. The observed keys
      to success for managers include staff education, modeling coaching behaviors,
      staff empowerment, self-directed work teams, and a willingness to give up
      traditional responsibilities.

PMID- 7627603
TI  - Preparing the workforce for managed care.
AB  - The role of the nurse manager in preparing the workforce for managed care is
      explored. Traditional and emerging roles of nursing care providers are examined
      for their current and potential contribution to patient care. Skills and
      strategies to be developed, and continuing education are identified.

PMID- 7627604
TI  - A model for implementing quality initiatives.
AB  - A multitude of quality improvement strategies exist. This article describes a
      model for implementing improvement strategies and describes the Nurse Manager's
      role in achieving quality improvements. The Quality Model illustrates the
      interactive processes among the four critical components of quality: culture,
      planning, measurement, and improvement. The Nurse Manager's role is that of
      leader in creating a culture that will support quality planning, measurement, and
      improvement.

PMID- 7627605
TI  - Rights and the Patient's Charter.

PMID- 7627606
TI  - Methods of rewarming the hypothermic patient in the accident and emergency
      department.
AB  - Hypothermia, occurring when the core body temperature falls below 35 degrees C,
      gives rise to life threatening physiological changes, and may present in the
      Accident and Emergency (A & E) department with varying aetiology and implications
      for nursing management. Rewarming the hypothermic patient is a priority of
      nursing care, and several different ways of achieving this are practised. This
      review of relevant literature aims to evaluate current methods of rewarming
      hypothermic patients commonly employed, their associated difficulties, and
      considers their potential implementation in the A & E setting.

PMID- 7627607
TI  - Emergency needlestick injury.
AB  - During the course of a year, there are many healthcare workers nationwide who
      sustain sharps injuries whilst carrying out their duties. Staff who work in the
      Accident and Emergency (A & E) units are no different from anyone else in this
      respect. The emotional cost of such an accident cannot be calculated, whereas the
      financial costs can. This article aims to show how the cost of an injury to a
      member of staff can be calculated, thus allowing a manager to assess the
      financial implications of sharps injuries to their department. In the absence of
      access to an Occupational Health (OH) department, most A & E units have to
      respond to sharps injuries to healthcare workers in the hospital. This task must
      be attended to by the medical staff as well as the nursing staff of the A & E
      unit. Within the following text the appropriate responses and methods to ensure
      uniformity of response are discussed. The tables and the calculation figures
      shown are taken directly from the information held in the St James's University
      Hospital Trust's OH department. All calculations are based on the middle band of
      the salary scale for each discipline. Accurate costings for each member of staff
      injured cannot be shown in this article, but the general principle is laid down
      and can be easily followed for any situation.

PMID- 7627608
TI  - Elder abuse and neglect: issues in the accident and emergency department.
AB  - Recognition and identification of elder abuse and neglect within the Accident and
      Emergency (A & E) department currently appears less evident than recognition of
      child abuse and domestic violence. As the population of older people increases,
      it is likely that there will be an increased usage of the A & E department by
      older people, some of whome may have been subject to abuse or neglect. Elder
      abuse and neglect constitute potentially serious health and social problems. The
      need for the A & E nurse to identify and respond to elder abuse and neglect is
      therefore a professional responsibility. The nursing profession is clearly in a
      position to contribute to the recognition of elder abuse and neglect, and A & E
      nurses are in a unique position to assist this process. This paper seeks to
      assist nurses with this task by arguing for a 'higher index of suspicion', allied
      to a sound knowledge base of the circumstances surrounding elder abuse, signs and
      symptoms and known risk factors. Finally, practical suggestions are offered to
      assist in the assessment and intervention with suspected or known cases of elder
      abuse and neglect.

PMID- 7627609
TI  - Conflicts of practice confronting second line nurse managers in an accident and
      emergency department. Part 2.
AB  - In recent times in Australia, there has been a proliferation of nursing career
      structures which aim to address the historical neglect of a career path for
      clinical nurses. Among these developments has been the formulation of a new and
      exciting nursing role, that of the second line nurse manager. This role was
      designed to give experienced nurses who traditionally worked 'in charge' formal
      recognition of their knowledge and skill, and sought to construct a role that
      encompassed both clinical and managerial responsibilities. However, the reality
      of these nurses' practice is fraught with problems and difficulties as they
      attempt to negotiate a new and uncharted domain. This paper recounts an action
      research study conducted by a group of second line nurse managers in an Accident
      and Emergency department, who sought to explore the dimensions of their practice.
      The study identifies problems with combining clinical and managerial
      responsibilities in the one role, within a context marked by a high level of
      unpredictability, and a culture which values clinical practice over other forms
      of nursing practice. The paper concludes with a number of recommendations to
      overcome these problems.

PMID- 7627610
TI  - I should have been with Lisa as she died.
AB  - A mother's experience of the death of her 23-year-old daughter, who died in the
      Accident and Emergency (A & E) department where access to the resuscitation room
      (and her daughter) were denied to her. This mother was a senior nursing sister in
      another department at the same hospital, and she subsequently wrote an open
      letter to the A & E department, outlining her experience of this traumatic event.
      It was her hope that this information might help to improve the situation for
      other families, who might have similar desires and needs, but might not feel they
      had the right or maybe the articulation skills to express them. Nursing and
      medical management made the decision not to circulate this open letter to other
      professionals in the department.

PMID- 7627611
TI  - An asthmatic in 'Wonderland': a patient's perspective of accident and emergency.

PMID- 7627613
TI  - Inappropriate--the patient or the service?
AB  - The inappropriate use of Accident and Emergency (A & E) departments by the public
      has been the subject of debate for many years. Patients often attend departments
      with problems which could equally have been treated by the primary care services
      in the community. However, despite much research into why patients choose to
      visit A & E departments rather than their general practitioners, efforts to
      reverse this trend have generally failed. If the professional view of what is
      appropriate cannot be enforced, perhaps the label 'inappropriate' belongs to the
      A & E services rather than the patient.

PMID- 7627612
TI  - Student nurses' perceptions of accident and emergency nursing: do they match the
      reality?
AB  - This study explores student nurses' perceptions of, and attitudes to, working in
      an Accident and Emergency (A & E) department prior to allocation there. An
      assessment of the students' actual experience within the department was then
      taken. This allowed the students' perceptions to be compared with the reality of
      the work. The sample consisted of all students training for part 10 of the
      register who were allocated to the unit over a 4-week period (n = 22). Data was
      collected by two self completion questionnaires, one given pre-allocation the
      second post-allocation, a 100% response rate was achieved for each. The results
      of the study indicate that students' perceptions of the A & E department do not
      match the reality of the work involved. These perceptions may cause increased
      anxiety and apprehension for students before they start in the department and
      this may hinder clinical learning. The results suggest that appropriate
      preparation prior to the period of clinical experience may help alleviate these
      difficulties.

PMID- 7627614
TI  - Roy's Adaptation Model and accident and emergency nursing.
AB  - This article aims to analyse Roy's Adaptation Model and to discuss its relevance
      to the Accident and Emergency (A & E) area. A brief description of a model of
      nursing will be given, initially, followed by an outline of the major concepts of
      Roy's Adaptation Model. An attempt will then be made to apply the Model to the
      care of a patient suffering severe chest pain who presents at the A & E
      department. Finally, the practicability of applying Roy's Model to A & E will be
      considered.

PMID- 7627615
TI  - Grief support in accident and emergency nursing: a literature review 1985-1993.
AB  - On completing a wide ranging review of literature related to Accident and
      Emergency (A & E) nursing, the authors chose to focus upon grief support. The
      literature ranges from personal experiences to large scale research. A table of
      studies is included to clarify major research findings in this area. The article
      concludes by recommending long term support for bereaved relatives and research
      to demonstrate the value of support for relatives in the community.

PMID- 7627617
TI  - Emergency care in the Shetland Islands.

PMID- 7627616
TI  - Pain relief and the accident and emergency nurse: the legal aspects.

PMID- 7627618
TI  - Land mines: the suffering of a nation.
AB  - For two nursing students, a long summer vacation provided an opportunity to gain
      some first hand experience of nursing in a developing country. The Kingdom of
      Cambodia, a country of approximately 9.3 million people in South East Asia, was
      the chosen destination. Here not only was a different culture encountered but
      also a hazard to public health which one would not usually encounter in the UK:
      the land mine.

PMID- 7627619
TI  - Who cares for Peter?

PMID- 7627620
TI  - Infection of baboons with simian/human immunodeficiency viruses.
AB  - Baboons were evaluated for their utility to serve as a model for testing envelope
      based vaccines against human immunodeficiency virus type 1 (HIV-1). The ability
      of HIV-1 strains IIIB, RF, and SF2 to infect baboons was compared with that of
      simian/human immunodeficiency virus (SHIV) recombinant viruses comprised of
      either HXB2 or SF2 env, tat, rev, and vpu genes inserted into the SIVmac239
      backbone. Both SHIV recombinants replicated in baboon PBMC in vitro, while no
      evidence of replication was noted for HIV-1 strains (MN, IIIB, SF2). Infection of
      baboons in vivo correlated with the restriction of infection in vitro. Virus was
      recovered by cocultivation methods early after SHIV (HXBc2) infection of two
      baboons with seroconversion profiles that parallel those observed in simian
      immunodeficiency virus (SIV)mac-infected rhesus monkeys. One of two baboons
      inoculated with SHIV(SF2) also seroconverted within 4 weeks; however, the
      kinetics of infection in a second animal appeared much later, with seroconversion
      to gp120 not evident until 20 weeks and no virus recovery during 32 weeks
      following infection. Viral DNA was detected in the lymph nodes of the SHIV
      inoculated animals by nested polymerase chain reaction (PCR) amplification.
      Histopathologic changes were evident in lymph nodes, yet no overt clinical
      disease was observed. When HIV-1 strains (IIIB, RF, and SF2) were inoculated into
      baboons, virus was not recovered and no seroconversion to the major HIV-1
      antigens was observed. However, viral DNA from the lymph nodes of four animals
      inoculated with HIV-1 strains could be detected by nested PCR, indicating a
      persistent but diminutive infection of HIV-1. The baboon thus represents a new
      animal model for testing HIV-1 envelope-based vaccines including the evaluation
      of new immunogens, dosages, routes, and adjuvants that act in eliciting
      protective responses.

PMID- 7627621
TI  - IL-10 synergizes with multiple cytokines in enhancing HIV production in cells of
      monocytic lineage.
AB  - Several cytokines, whose expression is increased in human immunodeficiency virus
      (HIV)-infected individuals, can enhance virus replication in CD4+ T lymphocytes
      and mononuclear phagocytes (MP). We have previously reported that interleukin
      (IL)-10 inhibited HIV replication in acutely infected monocyte-derived
      macrophages (MDM) at concentrations that completely blocked the production of
      endogenous tumor necrosis factor-alpha (TNF-alpha) and IL-6 from infected cells.
      In the present study, lower concentrations of IL-10, which were unable to
      completely suppress endogenous cytokines, paradoxically enhanced HIV replication
      in MDM induced by other cytokines. This synergistic induction of HIV expression
      by IL-10 in combination with TNF-alpha, IL-6, and other cytokines was also
      observed in the chronically infected promonocytic cell line, U1. The enhancing
      effect of IL-10 was correlated with an increase in HIV mRNA accumulation and
      potentiation of phorbol ester-induced long terminal repeat-driven transcription
      that was independent of the NF-kappa B and Sp1 transcription factors. Thus, IL-10
      is a cytokine capable of exerting complex regulatory effects on HIV expression in
      MP as a function of its own concentration and of the presence of other HIV
      regulatory cytokines.

PMID- 7627623
TI  - Mechanism of HIV persistence: implications for vaccines and therapy.
AB  - Periodic infusion of autologous HIV-antigen presenting cells (APCs), that
      stimulate the cytotoxic (CTL) response, while being incapable of producing virus,
      should lower viral burden and boost CD4+ count in HIV-seropositive individuals.
      Viral burden reasserts itself after antiviral therapy ceases or is interrupted
      for long. Therapy, therefore, would have to continue for life. These are
      predictions from a computer model of HIV-immune kinetics. The model equations
      describe the interactive kinetics of viral burden, CD4+ cell decline,
      neutralization of free virus by antibodies, infection of cells, and killing of
      infected cells by CTL. The computed trajectories of the kinetic equations
      reproduce the typical course of an HIV infection and the model yields several
      predictions that are not intuitively obvious, among them: (a) Persistence of HIV
      infection (failure of the immune system to clear infection) is an intrinsic
      property of the kinetics of the HIV-immune interaction. (b) The chronic state of
      infection is inherently stable, which means that the infection rebounds to the
      determined steady state, whenever antiviral therapy stops. (c) CTL is chronically
      activated, and the level correlates inversely with the avidity of neutralizing
      antibodies. (d) APCs have to be infused at a rate such as to boost and maintain
      the CTL response above the chronic level. Other therapies include CTL
      stimulation, via the macrophage route, by erythrocytes, into which MHC binding
      HIV-CTL epitope polypeptide fragments have been inserted; passive immunization,
      virion-trapping by CD4 analogs or CD4 expressing erythrocytes; and combination
      therapies with AZT, IL-2. These are also analyzed. Concerning HIV etiology, the
      model assumes that cells other than CD4+ cells (such as macrophages/monocytes)
      become infected, and contribute to the viral burden, and that infectible cells
      remain available even as CD4+ cells become exhausted. The model further assumes
      that CD4+ cells decline not only through direct killing by HIV and CTL, but by
      dysregulation and excess apoptosis caused by the presence of virus. The model
      predicts that persistence of HIV infection does not depend upon latently infected
      cells or escape mutants, as has been suggested.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7627622
TI  - Apoptosis-related mortality in vitro of mononuclear cells from patients with HIV
      infection correlates with disease severity and progression.
AB  - Peripheral blood mononuclear cells (PBMC) from 103 HIV-infected patients were
      tested for their mortality rate (MR) when incubated in vitro for 3 days in a
      culture medium. MR was related to apoptosis as shown by DNA analysis and
      morphological evaluation of ethidium bromide-stained PBMC by flow cytometry. MR
      was significantly higher in patients in CDC stage IV as compared to patients in
      stage II or III (p = 0.017). MR was also higher in patients with low CD4
      cells/mm3 (p = 0.014 for patients with < 400 cells; p = 0.001 for patients with <
      200 CD4 cells/mm3) and with low percentage of CD4 cells (p = 0.001 for patients
      with < 10% of CD4 cells). A significant negative correlation was observed between
      MR and both absolute numbers or percentages of CD4 cells (p < 0.001). The
      addition of interleukin-2 (IL-2) and fibro-blast-conditioned medium (FCM) to the
      cultures significantly reduced MR. However, the ability of both IL-2 and FCM to
      preserve viability was significantly associated with p24 negativity. Clinical and
      immunological follow-up was available for 60 patients for a mean period of 26
      months. MR at the beginning of the study was significantly higher in the group of
      patients who clinically progressed (according to the CDC classification) or died
      during the follow-up (p < 0.0001). Our data suggest that MR correlates with both
      disease severity and progression and that MR is directly related to the depletion
      of CD4 cells in cultures.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7627624
TI  - Increased mRNA expression of IL-6, IL-10, TNF-alpha, and perforin in blood
      mononuclear cells in human HIV infection.
AB  - Evidence has been presented for the involvement of various cytokines, including
      interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-alpha, in the
      pathogenesis of human immunodeficiency virus (HIV) infection. Since measured
      plasma levels may poorly reflect in vivo production of cytokines, we adopted in
      situ hybridization with cDNA oligonucleotide probes to enumerate blood
      mononuclear cells (MNCs) expressing mRNA for IL-6, IL-10, TNF-alpha, and
      perforin. The HIV-infected patients had elevated levels of MNCs expressing mRNA
      for all four cytokines compared to healthy controls. Numbers of IL-6 mRNA
      expressing cells were higher in patients with clinical AIDS than in asymptomatic
      seropositive patients, and correlated inversely with CD4+ cell counts in blood,
      reflecting the involvement of IL-6 in later stages of HIV infection. The
      described approach could be an alternative way to study cytokines in HIV
      infection.

PMID- 7627625
TI  - Serial HIV seroprevalence surveys: interpretation, design, and role in HIV/AIDS
      prediction.
AB  - To examine the potential role of seroprevalence surveys in HIV epidemic analysis
      and prediction, seroprevalence was modeled in terms of age- and time-specific
      incidence, while taking account of the differential inclusion of infected and
      uninfected individuals in serosurveys. Differential inclusion had two components,
      one reflecting disease progression and the other background demographic factors
      that could change over time. Seroprevalence and progression marker data generated
      by simulated epidemics showed that age dependence in HIV incidence is a key
      factor in data interpretation. Time trends in seroprevalence are difficult to
      interpret, and incidence cannot be estimated from these data unless the effects
      of disease progression on inclusion are taken into account. Furthermore, changes
      in incidence could be hard to distinguish from changes in background differential
      inclusion, casting doubt on the value of smaller sentinel surveys. Uncertainty
      about differential inclusion severely limits the value of seroprevalence data in
      improving the precision of HIV/AIDS prediction. Progression marker data are even
      harder to interpret, since changes in incidence will have effects on the marker
      value distribution, the size, direction, and timing of which are highly age
      dependent. Independent data on differential inclusion would enhance the value of
      data from seroprevalence surveys.

PMID- 7627626
TI  - Strategies for limiting the spread of HIV in developing countries: conclusions
      based on studies of the transmission dynamics of the virus.
AB  - Possible interventions to reduce the spread of human immunodeficiency virus (HIV)
      include actions that attempt to alter sexual behaviour, such as education aimed
      at reducing the rate at which individuals acquire new sexual partners, and
      methods that reduce the probability of transmission between partners, such as the
      promotion of condom use and the treatment of so-called "cofactor" sexually
      transmitted diseases. A mathematical model of HIV transmission that is able to
      mimic different approaches to the control of HIV transmission is employed to
      study the relative values of different approaches, either used in isolation, or
      in combination. The nonlinear nature of the term that describes the per capita
      rate of transmission dictates that for a given degree of intervention, the
      benefit accruing in terms of reduced HIV spread depends on the prevalence of
      infection before the introduction of control. Benefit is greatest when HIV
      prevalence is low. Combination approaches are predicted to be effective but the
      outcome is less than would be expected on the basis of simply summing the
      benefits resulting from each type of intervention used in isolation. The success
      of targeted interventions, aimed at those with high rates of sexual partner
      change, depends on the heterogeneity in levels of sexual activity within
      populations and what proportion of the population HIV is able to establish itself
      in. Targeted interventions are predicted to be very cost effective but their
      overall success in reducing HIV spread by a significant degree depends on the
      timing of their introduction (within the time frame of the development of the
      epidemic) and the pattern of mixing between different risk groups or sexual
      activity classes.

PMID- 7627627
TI  - Trends in HIV seroprevalence among persons attending sexually transmitted disease
      clinics in the United States, 1988-1992.
AB  - Trends in seroprevalence of the human immunodeficiency virus (HIV) were examined
      among patients attending sentinel clinics for sexually transmitted diseases
      (STDs) throughout the United States. Cross-sectional, unlinked (blinded) surveys
      of HIV seroprevalence were conducted annually within clinics in 40 metropolitan
      areas. From 1988 to 1992, 552,665 specimens were tested in 80 STD clinics. The
      overall HIV seroprevalence was 33% (range among metropolitan areas: 5-52%) among
      gay and bisexual men, 3% (range: 0.3-11%) among heterosexual men, 2% (range: 0.1
      11%) among women, and 10% (range: 0.5-45%) among heterosexual injecting drug
      users (IDUs). Controlling for clinic, age, and race/ethnicity, HIV seroprevalence
      decreased among all gay and bisexual men, but especially among white gay and
      bisexual men from 32% in 1989 to 22% in 1992. Among heterosexual men and women,
      HIV seroprevalence decreased among whites and, to a lesser degree, Hispanics, but
      remained essentially stable among African-Americans over time. Among heterosexual
      IDUs, seroprevalence was also unchanged. These results reflect changes in the HIV
      epidemic, which is becoming increasingly characterized by infected heterosexuals
      and IDUs, especially within minority populations.

PMID- 7627628
TI  - Lack of specificity of HTLV antibody enzyme immunoassays.

PMID- 7627629
TI  - Statistical techniques to evaluate the accuracy of Doppler sonographic diagnosis
      and prognosis.

PMID- 7627631
TI  - Ribozymes: biology, biochemistry, and implications for clinical medicine.
AB  - Ribozymes are a class of ribonucleic acid (RNA) molecules that possess enzymatic
      properties. Upon binding to complementary nucleic acid strands, catalytic
      degradation takes place via a cleavage reaction. In effect, inactivation of
      susceptible substrate RNA molecules takes place at a catalytic rate and with a
      high degree of substrate specificity. This article reviews the biology and
      biochemistry of this class of molecules and its potential applications in
      clinical medicine.

PMID- 7627630
TI  - Receptors and G proteins as primary components of transmembrane signal
      transduction. Part 1. G-protein-coupled receptors: structure and function.

PMID- 7627633
TI  - Interleukin 5 expressing allergen-specific T-lymphocytes in patients with house
      dust mite sensitization: analysis at a clonal level.
AB  - Interleukin 5 (IL-5) is a T-cell lymphokine known to stimulate development,
      functional activity, and in vitro survival of eosinophils. Tissue and blood
      eosinophilia occurring during allergic responses of the immune system are
      potentially mediated by IL-5 secreting T-cells. To test this hypothesis a series
      of allergen-specific T-cell clones were established from peripheral blood and
      skin lymphocytes of patients with atopic dermatitis and house dust mite
      sensitization. In addition, alloreactive T-cell clones were also prepared from
      peripheral blood lymphocytes of healthy donors. Cloned T-cells were analyzed for
      IL-5 mRNA expression and IL-5 secretion by means of in vitro gene amplification
      using the reverse transcriptase polymerase chain reaction and IL-5 specific
      oligonucleotide hybridization, as well as IL-5-specific ELISA. A majority of
      allergen-specific long-term cultured T-cell clones (84%) of different donors and
      of either phenotype (CD8+ or CD4+) disclosed IL-5 transcripts on stimulation with
      lectins. Almost all clones exhibiting IL-5 transcripts also released
      immunoreactive IL-5 protein into their culture supernatants. In contrast, only 2%
      of alloreactive T-cell clones obtained from healthy donors and none of
      alloreactive T-cell clones of one atopic patient investigated expressed
      detectable amounts of IL-5 mRNA in response to lectin stimulation, all of whom
      were CD4+. These results suggest that eosinophilia observed in allergic responses
      in the peripheral blood and in tissues at the site of induced late-phase
      cutaneous reaction may be associated with IL-5 release by allergen-specific T
      cells.

PMID- 7627632
TI  - Histological and ultrastructural findings in chloroquine-induced cardiomyopathy.
AB  - Light microscopic and ultrastructural findings in patients suffering from
      chloroquine-induced cardiomyopathy are reviewed. Based on our own observations in
      an autopsy case, functional and morphological similarities between chloroquine
      effects and hereditary lysosomal storage diseases are discussed.

PMID- 7627634
TI  - Graves' disease in HTLV-I carriers.
AB  - Three carriers of human T-lymphotropic virus type I (HTLV-I) with Graves' disease
      are reported. All three cases were complicated with uveitis, and one also showed
      chronic arthropathy. Anti-HLTV-I antibody was found in the serum by the particle
      agglutination method and western blotting, and HTLV-I proviral DNA was detected
      in peripheral lymphocytes by the polymerase chain reaction and Southern blotting.
      HTLV-I is a causal agent of adult T-cell leukemia and HTLV-I associated
      myelopathy/tropical spastic paraparesis, and is believed to be related to the
      pathogenesis of diseases such as chronic arthropathy, uveitis, chronic
      bronchoalveolitis, and Sjogren's syndrome. On the other hand, retrovirus
      infection is considered to cause autoimmune diseases. Thus, the pathogenesis of
      Graves' disease in the present patients might be associated with HTLV-I
      infection.

PMID- 7627635
TI  - Modulation of hemostatic balance with antithrombin III replacement therapy in a
      case of liver cirrhosis associated with recurrent venous thrombosis.
AB  - Patients with liver failure can present both thrombotic and hemorrhagic
      complications because of the deficiency in coagulation factors and inhibitors
      (protein C and S, antithrombin III) and impairment of fibrinolytic balance. Here
      we report the case of a 63-year-old man with liver cirrhosis, recurrent
      thrombosis, and features of low-grade consumption coagulopathy, showing severe
      antithrombin III deficiency (about 30% of normal values). Treatment with
      antithrombin III (2000 U/day) and low doses of heparin (5000 U b.i.d.) was
      successful in modulating the coagulation system toward an antithrombotic effect.
      After discharge from hospital the ambulatory treatment with antithrombin III
      concentrates (2000 U twice a week) allowed the attainment of antithrombin III
      activity of about 60% and prevented the patient from recurrence of venous
      thrombosis.

PMID- 7627636
TI  - Cancer gene therapy: principles, problems, and perspectives.
AB  - Despite enormous efforts focused on the development of new drugs and the use of
      novel drug combinations, including high-dose regimens supported by bone marrow
      and blood stem cell transplantation procedures, progress in the treatment of
      disseminated human cancer has been marginal. Remarkable advances in our
      understanding of the molecular biology of cancer has provided the possibility to
      employ new, selective tools of genetic intervention for more successful tumor
      treatment. We are now witnessing the inception of gene therapy. However, gene
      therapists face many drawbacks, including selectivity, specificity, sensitivity,
      and safety of gene transfer. Despite this there are already over 70 clinical
      protocols accepted for genetic approaches to cancer worldwide. Strategies
      currently under clinical investigation and discussed here include: (a) the
      enhancement of tumor immunogenicity by insertion of cytokine genes, genes coding
      for products of the major histocompatibility complex, and those for lymphocyte
      costimulatory ligands, (b) the vectoring of tumoricidal cytokines into cells that
      can potentially home on tumors to release their toxic products locally, (c) the
      use of tumor-specific pro-drug activators, i.e., the insertion of enzymatically
      pro-drug-activating genes fused to promoter systems which rely on differential
      (ideally tumorspecific) transcription control, (d) gene-marking strategies which
      may provide new indicators for minimal, residual, and relapsed tumor disease, (e)
      artificial repression of gene functions by insertion of genes encoding for
      complementary (antisense) mRNA to the gene of interest (e.g., oncogenes, drug
      resistance genes).

PMID- 7627638
TI  - Vectors derived from avian leukosis and sarcoma viruses.

PMID- 7627637
TI  - Adenovirus-mediated gene transfer into striated muscles.

PMID- 7627639
TI  - MDR gene transfer into live mice.

PMID- 7627641
TI  - Pilot study for the evaluation of T-cell-mediated tumor immunotherapy by cytokine
      gene transfer in patients with malignant tumors.

PMID- 7627640
TI  - Marker gene transfer into leukapheresis preparations containing hematopoietic
      progenitor cells: application in high-dose therapy rescued by reinfusion of
      peripheral blood hematopoietic progenitors in patients with multiple myeloma.

PMID- 7627642
TI  - Guidelines for the design and implementation of clinical studies in somatic cell
      therapy and gene therapy. The German Working Group for Gene Therapy.

PMID- 7627643
TI  - Popliteal aneurysms--the case for elective surgery "don't wait too long ...
      Norman Hertzer, 1986".

PMID- 7627644
TI  - Thrombolysis in arterial graft thrombosis.
AB  - OBJECTIVE: to assess the impact of peripheral arterial thrombolysis for vascular
      graft occlusion. DESIGN: Retrospective review. SETTING: University Hospital.
      MATERIALS: Thirty-one patients presented with 33 episodes of graft thrombosis.
      CHIEF OUTCOME MEASURES: Successful thrombolysis in terms of total clearance or
      sufficient clearance to reveal an underlying factor responsible for graft
      failure. MAIN RESULTS: Thrombolysis was successful in seven of 10 suprainguinal
      grafts (4 of 5 rtPA; 3 of 5 SK). One patient had failed lysis requiring an ilio
      femoral graft. Of the seven patients with successful lysis, one required revision
      of a proximal anastomosis, two required distal anastomotic revisions, and one
      rethrombosed. Twenty-three thrombosed infrainguinal grafts were managed initially
      with intraarterial thrombolysis (9rtPA, 14 SK). Of 27 patients surviving at 30
      days, seven required major amputation despite aggressive intervention.
      CONCLUSIONS: Thrombosed suprainguinal grafts are amenable to thrombolysis and
      adjunctive surgery when necessary, with no major haemorrhagic complications. The
      majority of patients with thrombosed infrainguinal grafts require surgical
      intervention in order to preserve, or establish long term patency. For
      polytetrafluoroethylene (PTFE) grafts, thrombolysis was associated with poor
      success, haemorrhagic complications and a high amputation rate.

PMID- 7627645
TI  - Predicting of postoperative cardiac events using ambulatory ECG monitoring prior
      to abdominal aortic surgery.
AB  - OBJECTIVES: The purpose of this study was to estimate the value of preoperative
      electrocardiographic (ECG) monitoring in predicting postoperative cardiac events
      in patients undergoing abdominal aortic surgery. DESIGN: A prospective open
      study. SETTING: University Hospital. MATERIALS: One hundred consecutive patients
      were studied before aortic or aortofemoral surgery by ambulatory ECG monitoring
      for 24 hours. CHIEF OUTCOME MEASURES: An ischaemic episode by ECG criteria was
      defined as a > or = 1 mm horizontal or downsloping ST segment depression measured
      60 msec after the J point and persisting for at least 40 sec. MAIN RESULTS:
      Twenty-four patients had preoperative ambulatory ischaemia. Twenty patients had
      postoperative cardiac events including three with fatal myocardial infarction,
      one with a nonfatal infarction, eight with unstable angina, three with pulmonary
      oedema and five with atrial fibrillation. Sixteen out of 24 (67%) patients with
      ambulatory ischaemia had postoperative cardiac events (p < 0.01). Only four
      events occurred among 76 patients without ischaemia (p < 0.005). The sensitivity
      of ambulatory ischaemia predicting cardiac events was 80% with a specificity of
      90%, the predictive value of ischaemia was 67% and the predictive value of a
      negative result was 95%. CONCLUSIONS: Preoperative ECG monitoring for myocardial
      ischaemia could non-invasively identify patients at high risk for postoperative
      cardiac morbidity and mortality after vascular surgery.

PMID- 7627646
TI  - The use of a simple clinical cardiac risk index predictive of long-term outcome
      after infrarenal aortic reconstruction.
AB  - OBJECTIVE: Assessment of the value of preoperative clinical cardiac risk score
      (Detsky) in predicting long-term outcome in terms of survival and quality of life
      after elective aortic reconstruction. DESIGN: Prospective assessment of cardiac
      risk factors using Detsky's modification of Goldman's Index. SETTING: District
      General Hospital. MATERIALS: Ninety-three consecutive patients undergoing
      elective infrarenal aortic reconstruction. CHIEF OUTCOME MEASURES: After a median
      follow-up of 50.5 months, surviving patients were interviewed to assess quality
      of life using a standard Rosser classification. MAIN RESULTS: A high pre
      operative cardiac risk score (Detsky > 10) was associated with decreased
      probability of survival, increased likelihood of suffering a non-fatal
      cardiovascular event, and diminished quality of life at the time of assessment.
      CONCLUSIONS: Preoperative cardiac risk assessment is helpful in predicting long
      term outcome.

PMID- 7627647
TI  - Histopathological characteristics of explanted human prosthetic arterial grafts:
      implications for the prevention and management of graft infection.
AB  - OBJECTIVE: to study the histopathological characteristics of prosthetic vascular
      graft infection. DESIGN: prospective clinical study over 2 years. SETTING:
      University Hospital. MATERIALS: 36 infected and 29 uninfected (control)
      chronically implanted vascular prostheses (half aortic) were removed and 352
      sections prepared. CHIEF OUTCOME MEASURES: light microscopy (multiple stains),
      scanning electron microscopy (SEM), and multiple culture techniques to identify
      characteristics of healing, infection, and microorganisms. MAIN RESULTS: Acute
      inflammation (AI) (neurophils, granulocytes and necrosis) were seen in 75% of
      infected grafts, were most prominent in the perigraft tissue and rarely seen on
      the luminal surface. These were usually well localised, leaving the remainder of
      a graft well incorporated with no signs of infection. In 25% of clinically
      infected, culture-positive grafts there was no significant acute inflammation.
      Chronic inflammation (CI) (macrophages, lymphocytes, monocytes, giant cells) was
      seen in 70% of both control and infected grafts. In 50% of both groups a
      significant lymphocytic population was composed exclusively of T-lymphocytes
      suggesting a true host vs graft response. Unincorporated chronically implanted
      grafts (> 1 yr) were seen with equal frequency in the two groups although more
      diffusely unincorporated grafts were infected. Microorganisms were cultured from
      23 infected grafts (64%) and were, at microscopy, mostly found outside the graft
      and nerves on the luminal side. CONCLUSIONS: This data cast doubt on criteria
      commonly used to distinguish graft infections and host vs. graft reactions from
      normal graft healing. Acute and chronic inflammation are not predictive of
      infection.

PMID- 7627648
TI  - An in vivo model for studying the local haemodynamics of end-to-side anastomoses.
AB  - OBJECTIVES: To develop an in-vivo model to study the anastomotic flow patterns.
      DESIGN: Prospective, open, animal study. METHODS: Polyurethane grafts with an
      internal diameter equal to the abdominal aorta (8 mm) of 90 kg pigs were
      implanted as bypass grafts from the supra-renal to the infra-renal level. A novel
      technique for constructing anastomoses with different anastomosis angles and only
      slight dilatation was used. The proximal outflow segment was occluded and the
      flow rate through the graft controlled by clamping the iliac arteries.
      Visualisation of the flow-fields at the distal end-to-side anastomosis was
      achieved by a comprehensive colour Doppler mapping protocol. RESULTS: The
      angulation of the anastomoses was controllable and reproducible. Gross
      haemodynamic parameters were stable within physiological ranges and were typical
      for peripheral bypass grafts. The flow fields at the distal end-to-side
      anastomosis were visualised and found to be in accordance with those reported by
      in vitro studies. Using different angles of Doppler insonation the same flow
      field characteristics were found. CONCLUSIONS: The model is an appropriate tool
      for studies of the effects of anastomotic geometry on local flow fields in vivo.

PMID- 7627649
TI  - Influence of low dose allopurinol on ischaemia--reperfusion injury during
      abdominal aortic surgery.
AB  - OBJECTIVES: To ascertain whether surgery causes ischaemia-reperfusion (I-R)
      related injury, if this injury is augmented by preoperative shock, and reduced
      with low dose allopurinol. DESIGN: Randomised blind placebo controlled trial.
      SETTING: Surgical laboratory. MATERIAL AND METHODS: 22 pigs were randomly
      allocated to four groups; OP = operation/placebo, OA = operation/ allopurinol,
      SOP = shock + operation/placebo, SOA = shock + operation/allopurinol. An aortic
      tube prosthesis was inserted in all. In groups SOP and SOA preoperative shock was
      induced by exsanguination. Allopurinol was administered in group OA on the
      preoperative day and peroperatively, in group SOA during shock and
      peroperatively. CHIEF OUTCOME MEASURES: Perioperative blood concentrations of
      thiobarbituric acid reactive species (TBARS), ascorbic acid (AA), albumin, 99mTc
      albumin and creatine phosphokinase (CPK) as indicators of oxidative membrane
      damage, antioxidant activity, microvascular permeability changes and muscular
      cell damage respectively. MAIN RESULTS: In the OP and OA groups TBARS gradually
      increased, while AA, 99mTc-albumin and CPK remained unchanged and albumin
      decreased. No effect of allopurinol was observed in these groups. In the SOP
      group TBARS and AA were not significantly different from groups OP and OA. Yet,
      albumin, 99mTc-albumin and CPK decreased significantly more in the SOP group.
      Compared with the SOP group, allopurinol treatment (SOA) produced lower TBARS and
      higher AA levels, and reduced the effect of shock on albumin, 99mTc-albumin and
      CPK concentrations. CONCLUSIONS: Aortic surgery causes no I-R related damage. Pre
      operative shock produces I-R related damage, which is reduced by allopurinol.

PMID- 7627650
TI  - The distribution of peripheral vascular disease in a Dutch Caucasian population:
      comparison of type II diabetic and non-diabetic subjects.
AB  - OBJECTIVES: To study the distribution of peripheral vascular disease and the
      relationship to diabetes. DESIGN: Prospective population based study of Dutch
      caucasian inhabitants. METHODS: From a total of 10,500 subjects aged between 50
      and 75 years, 2484 Caucasian inhabitants were screened with respect to their
      glucose tolerance. Subjects using oral antidiabetic agents or insulin were
      classified directly as having diabetes mellitus. The other participants were
      screened using two oral glucose tolerance tests and classified using WHO
      criteria. A group of 173 people with diabetes and a representative age/sex
      stratified sample of 288 non-diabetic subjects were seen in the vascular
      laboratory. Carotid artery disease was investigated with Duplex scanning, arm and
      leg artery obstructions with real time frequency analysis of continuous wave
      Doppler signals and indirect blood pressure measurements. RESULTS: Comparing
      diabetic with non-diabetic subjects, we found significantly more obstructions of
      the carotid arteries (8.7 vs 2.8%), arm arteries (2.3 vs 0%), as well as leg
      arteries (31.8 vs. 18.4%). The same holds if only the crural artery obstructions
      were compared (23.7 vs 16.0%). Two of the four diabetic subjects with arm artery
      obstructions had retrograde vertebral flow, three of them had carotid artery
      obstructions as well, and three also had leg artery obstructions. More than half
      of the subjects with a carotid artery obstruction, also had leg artery
      obstructions. CONCLUSIONS: Peripheral vascular disease is common in diabetes, but
      most are asymptomatic.

PMID- 7627651
TI  - The changing workload of a surgical unit with a vascular interest.
AB  - OBJECTIVES: To examine the changing relationship between general and vascular
      surgical workload on a vascular "firm", over a 6-year period. DESIGN:
      Retrospective review. SETTING: Leicester Royal Infirmary and Professorial
      Surgical Unit, U.K. 1987-1992. METHOD: Analysis of audit of all surgical
      admissions. Relation of vascular surgery to general surgery. RESULTS: There has
      been a slight decrease (5%) in the number of general surgical elective
      admissions. Overall, the number of general surgical admissions, both elective and
      emergency, show a slight increase of about 3%. In contrast the number of vascular
      admissions increased by 42%. Of the general surgical procedures carried out 75.9%
      were either minor or intermediate, whereas 92.5% of vascular procedures were
      coded as major or higher. There has been a three times increase in the number of
      carotid endarterectomies, a similar increase in the number of the femorodistal
      bypass grafts and a halving of the number of major amputations. There has also
      been a five times increase in the number of angioplasties carried out.
      CONCLUSIONS: Our figures show the progressive, rapid increase in vascular
      surgical workload, compared to general surgery, and the need for the continued
      expansion of vascular surgery as a speciality.

PMID- 7627652
TI  - Surgery for limb threatening ischaemia: a reappraisal of the costs and benefits.
AB  - OBJECTIVES: To study the quality of life of patients following surgery for
      critical limb is ischaemia. DESIGN: Part retrospective, part prospective open
      study. SETTING: Vascular unit of a University Hospital. MATERIALS: Seventy-nine
      consecutive patients, medium age 75 years (range 44 to 94), who presented with
      leg threatening ischaemia and who underwent successful revascularisation or a
      major amputation were studied. CHIEF OUTCOME MEASURES: Six separate quality of
      life measures were recorded at 6 months: pain, mobility, anxiety, depression,
      activities of daily living (Barthel) and lifestyle (Frenchay). MAIN RESULTS: The
      mortality of this group of patients after six months was 24%. Forty-seven
      patients were available for quality of life assessment six months after initial
      intervention. Overall, amputation was more costly than successful
      revascularisation and limb salvage. Limb salvage resulted in greater mobility (p
      < 0.001) and better performance in self-care (p < 0.001) and lifestyle (p =
      0.006), but produced more anxiety and depression (p = 0.04) than major
      amputation. A subgroup of patients who had major amputation after a failed limb
      salvage operation consumed a disproportionate amount of resources and, although
      their mobility was typical of amputees, their self-care and lifestyle scores were
      similar to those who had successful limb salvage. OBSTRUCTIONS: Limb salvage is
      attempted in up to 22% of patients for whom primary amputation may provide more
      expeditious rehabilitation with minimal impairment of their lifestyle
      performance.

PMID- 7627653
TI  - Changes in postocclusive reactive hyperaemic values as measured with laser
      Doppler fluxmetry after infrainguinal arterial reconstructions.
AB  - OBJECTIVES: The aim of the present study was to evaluate microcirculartory
      changes of the postocclusive reactive hyperaemia test measured with Laser Doppler
      fluxmetry to detect results of arterial reconstructions. DESIGN: Prospective open
      study. SETTING: Vascular laboratory of a University Hospital. MATERIAL: Sixty
      patients with peripheral arterial occlusive disease who underwent infrainguinal
      reconstruction were examined the day before and 1-2 days after surgery. CHIEF
      OUTCOME MEASURES: The values were obtained during postocclusive reactive
      hyperaemia induced by release of a 3 min arterial occlusion with a cuff at ankle
      level with the laser Doppler probe placed dorsally on the first toe. The
      alterations after surgery in these hyperaemia parameters were compared to changes
      in ankle/brachial index and clinical improvement at 30 days postoperatively. MAIN
      RESULTS: Patients improved by surgery according to ankle/brachial index had
      significantly reduced time to peak (p < 0.001) and significantly increased
      resting flux value (p < 0.05) and peak flux value (p < 0.05). There was a
      significant correlation between the change after surgery in time to peak flux and
      increment of ankle/brachial index (r = 0.63, p < 0.001). CONCLUSIONS: Changes in
      reactive hyperaemia values as measured with laser Doppler fluxmetry, especially
      the time to peak flux, seem to detect circulatory changes caused by arterial
      reconstructions.

PMID- 7627654
TI  - Venous haemodynamics and the occurrence of leg oedema in patients with popliteal
      aneurysm.
AB  - OBJECTIVES: To see whether popliteal aneurysms cause venous obstruction and to
      investigate leg oedema and DVT following repair. DESIGN: Prospective open
      clinical study. SETTING: University Department of Surgery. MATERIALS: 8 patients
      undergoing popliteal aneurysm repair in 9 legs (1 bilateral repair). CHIEF
      OUTCOME MEASURES: CT and plethysmographic evidence of vein compression, the
      occurrence of postoperative leg oedema and phlebographic evidence of deep venous
      thrombosis (DVT). MAIN RESULTS: Preoperative CT investigation showed that the
      aneurysm compressed the popliteal vein in 6/9 limbs where surgery was planned and
      in 9/10 limbs with popliteal aneurysms (patent or occluded) of > 2 cm diameter (p
      < 0.01). However, on the CT image, increased collateral network could be observed
      and most patients had normal venous drainage prior to operation as assessed by
      air plethysmography. Postoperatively, leg volume was measured by the formula of a
      truncated cone. Following vascular reconstruction, leg volume increased by 23%.
      Except for one patient with a confirmed DVT preoperatively, postoperative venous
      congestion and DVT was not observed in the operated leg as assessed by
      phlebography and plethysmography. CONCLUSIONS: Popliteal artery aneurysms "2 cm
      diameter usually compress and dislocate the popliteal vein prior to operation.
      However, sufficient venous drainage is maintained, possibly because of an
      increased collateral venous network. Disruption of lymph channels with secondary
      lymphoedema is probably the most important mechanism behind the leg swelling
      observed in patients following popliteal aneurysm repair.

PMID- 7627655
TI  - The additional value of intraoperative angiography in infragenicular
      reconstruction.
AB  - OBJECTIVE: To evaluate the ability of preoperative intraarterial digital
      subtraction angiography (IADSA) to predict the feasibility of infragenicular
      reconstruction and site of the distal anastomosis. DESIGN: Prospective study.
      SETTING: University Hospital MATERIALS: 45 patients with 50 ischaemic limbs,
      considered potential candidates for infragenicular reconstruction. CHIEF OUTCOME
      MEASURES: Pre-reconstruction intraoperative angiography (IOA) was used as the
      gold standard. Analysis of angiograms was performed blindly and independently by
      a single observer. In patients who ultimately underwent primary amputation,
      exploration and attempted angiography of the crural and ankle vessels was
      performed to verify the IADSA findings. MAIN RESULTS: There was 87% accuracy
      (kappa = 0.66) between IADSA and IOA in differentiating between a normal,
      stenosed and occluded tibial artery and there was 86% accuracy (kappa = 0.67) in
      determining the adequacy of run-off into the pedal arch. IADSA had a positive
      predictive value of 100% to determine the feasibility of reconstruction but a
      negative predictive value of only 73%. After excluding those patients tha IADSA
      deemed non-reconstructable, IADSA had a positive predictive value of 97% to
      determine the correct artery and 92% to determine the correct segment of artery
      for distal anastomosis. CONCLUSIONS: IADSA could not determine when
      reconstruction was not possible, but in those deemed reconstructable by IADSA,
      the surgeon can confidently expose the appropriate artery at the appropriate
      level knowing the pedal run-off status in 86% of patients. IADSA should not be
      used to exclude reconstruction (i.e. pre-reconstruction IOA is still required in
      these patients) but for the remainder, IADSA can be used to plan surgical
      strategy without recourse to IOA.

PMID- 7627656
TI  - Impedance analysis compared with Quickscan in the detection of graft-related
      stenoses.
AB  - OBJECTIVE: To compare two methods of detecting graft stenoses after infrainguinal
      bypass. DESIGN: Prospective study. SETTING: Vascular Laboratory, University
      Hospital. MATERIALS: 110 infrainguinal graft studies (60 vein, 50 PTFE) in 74
      patients were performed prospectively to detect graft-related stenoses. CHIEF
      OUTCOME MEASURES: The diagnostic accuracy of computer assisted impedance analysis
      was assessed using Quickscan (QS) as the gold standard in the detection of graft
      related stenoses. CHIEF RESULTS: QS showed occlusion in 4 grafts (two vein and
      two PTFE), no stenosis in 86 graft studies and stenoses in 20 studies. All 12
      stenoses with a frequency ratio > or = 1.4, were confirmed with intraarterial
      digital subtraction angiography (IADSA). Eight stenoses with a frequency ratio of
      1:3 continued graft surveillance. The median thigh impedance score of vein grafts
      with QS confirmed stenoses was 0.51 (0.36-0.70) compared with 0.44 (0.30-0.60)
      for non-stenosed vein grafts (p = 0.015, Mann-Whitney U test). The median thigh
      impedance score in PTFE graft with QS confirmed stenosis was 0.58 (0.53-0.76)
      compared with 0.42 (0.28-0.73 for non-stenosed grafts (p = 0.0001). An impedance
      score > 0.45 has been suggested for detection of "at risk" grafts. Using QS as
      the gold standard, impedance assessment gave 90% sensitivity, 63% specificity in
      the thigh; 80%, 52% in the calf and 90%, 46% taking the higher score on calf for
      thigh data. Taking a QS frequency ratio of 1:4 as indicating a significant
      stenosis (50% diameter reduction), 11% (12/106) of surveillance studies went on
      to intervention, that is 12/74 (16%) grafts. CONCLUSIONS: If the higher impedance
      score derived from either the calf or thigh was used to detect stenoses, 60%
      (64/106) of graft studies would have been referred for intervention. We believe
      this high level of intervention is unrealistic and cannot therefore recommend
      impedance analysis for graft surveillance.

PMID- 7627657
TI  - The influence of the adventitia on the presence of smooth muscle cells and
      macrophages in the arterial intima.
AB  - OBJECTIVE: To test the hypothesis that atherosclerosis may be initiated by
      hypoperfusion or thrombotic occlusion of the adventitial vasa vasonum. DESIGN: In
      a new model of atherogenesis, an early atherosclerotic lesion may be initiated by
      removal of the adventitia from the carotid artery of the New Zealand White
      rabbit, wherein lie the vasa vasorum. SETTING: Animal laboratory, University
      Department of Surgery and Medicine. CHIEF OUTCOME MEASURES: Immunocytochemistry
      was undertaken to demonstrate the presence of smooth muscle cells and macrophages
      within the intimal lesions. Smooth muscle cells were labelled with a monoclonal
      antibody designated HHF35 and macrophages were labelled with a rabbit specific,
      macrophage specific antibody, RAM11. CHIEF RESULTS: In rabbits fed a normal diet,
      at day 14, the intimal lesion was composed exclusively of smooth muscle cells. By
      day 28, such lesions had regressed. In rabbits fed a high cholesterol diet, at
      day 14, the intimal lesion was composed of a mixture of macrophages and smooth
      muscle cells. By day 42, the pattern of cellular distribution was such that
      macrophages (present as foam cells) were predominant. In the presence of
      persistent hypercholesterolaemia these lesions did not regress. CONCLUSIONS: This
      new model can produce two different cellular responses that may mimic the intimal
      lesions seen with re-stenosis after angioplasty or in hypercholesterolaemic man
      and as such, might be useful in separating out these two different
      pathophysiologies.

PMID- 7627658
TI  - Systemic endotoxaemia and fibrinolysis during aortic surgery.
AB  - OBJECTIVE: To determine whether endotoxaemia and activation of the systemic
      fibrinolytic system occurs during and after aortic surgery. DESIGN: Prospective
      clinical study. SETTING: University Hospital. MATERIALS: 31 patients undergoing
      aortic surgery. CHIEF OUTCOME MEASURES: Venous blood assay for endotoxin and
      plasminogen activator inhibitor-1 (PAI-1). Samples were obtained preoperatively,
      immediately before and 5 minutes after cross-clamp application and removal, and
      at 2, 4, 6 and 24 hours postoperatively. Tonometric sigmoid intramural pH was
      monitored throughout this period as a means of detecting colonic mucosal
      ischaemia. MAIN RESULTS: Endotoxin levels increased after clamping of the aorta,
      peaking immediately before clamp removal, mean value 34.5 pg/ml, p < 0.01, but
      returning to preoperative levels by 24 hours. PAI-1 levels progressively
      increased after surgery, with persistently high levels remaining at 24 hours (p <
      0.01). CONCLUSIONS: Endotoxaemia does occur during aortic surgery and appears to
      be associated with activation of the systemic fibrinolytic system.

PMID- 7627659
TI  - A comparison of clinical index and ejection fractions in predicting cardiac
      complications following infrarenal aortic reconstruction.
AB  - OBJECTIVE: To compare the Detsky clinical cardiac risk index with ejection
      fraction measurements in predicting postoperative cardiac events. DESIGN:
      Prospective study. SETTING: District General Hospital. MATERIALS: 48 patients
      undergoing infrarenal aortic reconstruction. CHIEF OUTCOME MEASURES: Ejection
      fractions were measured both by echocardiography and a technetium 99 MUGA scan.
      MAIN RESULTS: Three patients developed four major cardiac events (LVF three,
      fatal myocardial infarction one). Fourteen patients experienced 15 minor cardiac
      events (arrhythmia 11, ST segment depression four). The clinical index predicted
      postoperative cardiac problems (p = 0.0001). There was no correlation between
      ejection fraction measurement and postoperative cardiac events nor between
      ejection fraction measurements and the clinical index. Combining the index with
      ejection fraction measurement provided no additional information over the index
      alone. CONCLUSIONS: Calculation of a clinical index before aortic reconstruction
      is a simple and reliable way of selecting patients who are at risk of developing
      postoperative cardiac events.

PMID- 7627660
TI  - Trends in abdominal aortic aneurysms: a 13 year review.
AB  - AIM: To assess changing trends of abdominal aortic aneurysms 1979-1991. DESIGN:
      Retrospective study from the Leicestershire Health Authority. RESULTS: 727
      patients with abdominal aortic aneurysm were treated. Of these 56.4% were
      admitted for elective repair and 43.6% presented with rupture. There was a
      significant increase in the number of ruptured aortic aneurysms over this period
      despite an increase in the number of elective repairs. The overall 30-day
      mortality of elective repair (including patients with symptomatic but non
      ruptured aneurysms) was 8.8%. The overall 30-day mortality of ruptured aneurysms
      (including patients who were deemed medically too unfit for surgery) was 57.7%.
      There has been no significant change in elective and ruptured mortality over the
      study period. There was a significant increase in the median age of patients
      (69.5 yrs in 1979 to 74 yrs in 1991). CONCLUSION: The increasing incidence of
      abdominal aortic aneurysms may reflect better diagnostic methods, greater
      clinical awareness of the condition and increase in the proportion of elderly
      people in the population.

PMID- 7627661
TI  - Vanishing popliteal entrapment.

PMID- 7627662
TI  - Pseudoaneurysm of the thoracic aorta: missed traumatic rupture.

PMID- 7627663
TI  - Recurrent cellulitis after femoropopliteal bypass surgery in saphenous
      phlebectomy limbs.

PMID- 7627664
TI  - Treatment of major aortic graft infection: preliminary experience with total
      graft excision and in situ replacement with a rifampicin bonded prosthesis.

PMID- 7627665
TI  - Community mental health centers: success or failure?

PMID- 7627666
TI  - How to help psychiatric patients stop smoking.

PMID- 7627667
TI  - Dilemmas in professional collaboration with consumers.

PMID- 7627668
TI  - Can the clinician predict suicide?

PMID- 7627669
TI  - Building an empirically based outcomes information system for managed mental
      health care.

PMID- 7627670
TI  - Factors associated with admission to public and private hospitals from a
      psychiatric emergency screening site.
AB  - OBJECTIVE: The study examined factors associated with admission to public and
      private hospitals from a mental health care emergency screening system operating
      under a longstanding mandate to maximize use of private inpatient treatment.
      METHODS: For 206 patients evaluated at the mental health emergency screening site
      over a two-and-a-half-month period, data were collected on demographic and
      clinical characteristics, admission history, services received during the
      emergency encounter, system variables such as time the patient spent at the
      emergency screening site, number of admission sites asked to accept the patient,
      and all reasons cited by providers for refusing to admit the patient. Logistic
      regression was used to develop a model of factors most likely and least likely to
      be associated with private hospitalization. RESULTS: Overall, 60 percent of the
      sample was refused admission by one or more providers, and 55 percent, who were
      not accepted by and private hospital, became public patients. Private hospital
      admission was associated with patient or family involvement in referral and
      disposition, private or Medicaid insurance, a presenting problem of depression or
      suicidality, and longer time spent at the emergency screening site. Public
      admission was associated with no insurance, a past history of major public
      hospitalization, current or past history of assaultiveness, a presenting problem
      of aggression, and lack of any discharge site. CONCLUSIONS: Private providers are
      reluctant to admit patients who have characteristics associated with public
      hospitalization. In the restructuring of health care, a more fully privatized
      system will likely be called on to absorb such patients. Their care, treatment,
      and impact on the system should be carefully monitored and evaluated.

PMID- 7627671
TI  - Risk management strategies in the provision of mental health services.
AB  - Psychiatric settings provide unique challenges for engaging in risk management
      activities. The author reviews principles of risk management--the systematic
      effort to avoid harm to patients and the subsequent threat of financial loss--as
      they apply to mental health organizations, including preconditions necessary for
      a risk management process, identification of risk, evaluation of risk, and the
      actual risk management process. He outlines recent relevant directions of the
      Joint Commission on Accreditation of Healthcare Organizations, especially the
      shift to continuous quality improvement and the organization of the 1995
      standards around major functions such as improving performance. Today few mental
      health care organizations can afford not to have programs that actively seek to
      reduce and eliminate risk, the author believes, not only because of the financial
      consequences to the organization but also because a solid risk management program
      can significantly improve patient care.

PMID- 7627672
TI  - A comparative analysis of family caregivers' perceived relationships with mental
      health professionals.
AB  - OBJECTIVE: Family caregivers' relationships with mental health professionals who
      provided care for their mentally ill relative were examined to identify changes
      in types of contacts and levels of satisfaction over time and differences among
      caregiver groups. METHODS: White upper-middle-class members of a family support
      group surveyed by mail in 1991 to obtain information about their contacts with
      mental health professionals and their opinions about needed supports and
      services. Data from the 1991 survey were compared with data from a similar group
      of caregivers surveyed in 1983 and from a 1990-1991 study of white and black
      caregivers in lower socioeconomic groups. RESULTS: The analysis showed that a
      significant minority of caregivers continue to be dissatisfied with their
      contacts with mental health professionals. The 1991 survey found that
      professionals did not actively involve caregivers in the treatment of their
      mentally ill family member, and caregivers ranked more communication with
      professionals as their greatest need. Few differences were found between
      caregiver groups in types of professional contact or levels of satisfaction.
      However, caregivers in the lower socioeconomic groups in the 1990-1991 study
      received more advice from professionals than did support group members in the
      1991 survey, and black caregivers were significantly more satisfied with their
      professional contacts than support group members in the 1991 survey. CONCLUSIONS:
      Partnerships between family caregivers and mental health professionals must be
      developed and nurtured to address caregivers' unmet needs.

PMID- 7627673
TI  - Symptom severity and number of previous psychiatric admissions as predictors of
      readmission.
AB  - OBJECTIVE: The study examined factors predicting early readmission (within 30
      days of discharge) to a state hospital. METHODS: A total of 189 patients with
      acute symptoms who were admitted to a state hospital were evaluated at discharge
      using the Brief Psychiatric Rating Scale (BPRS) and the Nurses Observation Scale
      for Inpatient Evaluation (NOSIE). Patients who were readmitted within 30 days
      were compared with those who were not on BPRS and NOSIE ratings and on other
      variables, including length of stay, number of previous admissions, demographic
      characteristics, and diagnosis. RESULTS: Scores on the thought disorder factor
      and self-neglect question on the BPRS and the number of previous admissions were
      significantly higher among patients who where readmitted within 30 days of
      discharge. The variables correctly predicted readmission for 86 percent of cases
      in the study. CONCLUSIONS: The characteristics of high scores at discharge on the
      BPRS thought disorder factor and the BPRS item on self-neglect, along with a high
      number of previous admission, may be helpful in identifying patients at risk for
      readmission to inpatient psychiatric settings.

PMID- 7627674
TI  - Occurrence of seizures related to psychotropic medication among psychiatric
      inpatients.
AB  - OBJECTIVE: Seizures associated with psychotropic medication are serious and
      reportable adverse drug reactions. This study examined the occurrence of seizures
      associated with psychotropic medication during psychiatric hospitalization.
      METHODS: Among 10,994 admissions to a psychiatric teaching hospital over a 30
      month period between 1990 and 1993, 29 patients were identified by a specially
      trained quality assurance nurse as having seizures that were probably related to
      psychotropic medication. These cases were verified by a clinical pharmacist and a
      psychopharmacologist. Two patients were excluded, and the records of 27 patients
      were reviewed in detail. RESULTS: Nineteen of the 27 patients (70 percent) whose
      seizures were related to psychotropic medication had a preexisting seizure
      disorder, and eight had new-onset seizures. Psychotropic medications were
      primarily implicated as being associated with seizures in the cases of three of
      the 19 patients with preexisting seizure disorders (15.8 percent) and five of the
      eight patients with new-onset seizures (62.5 percent). In the group with
      preexisting seizure disorders, six patients (32 percent) had subtherapeutic blood
      levels of antiseizure medication, and four (21 percent) experienced
      pseudoseizures. CONCLUSIONS: Seizures among inpatients on psychotropic medication
      were infrequent (.3 percent of psychiatric admissions); the majority (70 percent)
      occurred in patients with preexisting seizure disorders. Seizures were directly
      attributed to psychotropic medications in less than .1 percent of admissions.

PMID- 7627675
TI  - Anxiety disorders among patients in a general emergency service in Israel.
AB  - OBJECTIVE: Several studies have suggested that many patients with anxiety
      disorders present in nonpsychiatric medical settings such as primary care
      facilities, emergency services, and general practice. This study examined the
      prevalence of panic disorder and generalized anxiety disorder among patients
      admitted to the general emergency service at an urban medical center in Israel.
      METHODS: Four groups totaling 517 patients were assessed. The groups consisted of
      patients presenting with somatic complaints for whom no physical condition was
      diagnosed, patients with somatic complaints found to have a physical disorder, a
      group of nonpsychiatric consecutive admissions to the emergency service, and a
      group of referrals to the psychiatric emergency service. RESULTS: The prevalence
      of panic disorder and generalized anxiety disorder in the entire sample was 2.7
      percent, which is comparable to the prevalence rates reported in various
      community studies. However, the prevalence among patients with somatic complaints
      but no physical disorder was 6.7 percent, significantly higher than in the
      nonpsychiatric comparison groups. The prevalence in the group of psychiatric
      referrals was 4.8 percent. CONCLUSIONS: A population at risk for higher
      prevalence of anxiety disorders can be identified among patients seen in an
      emergency service. Physicians in primary care settings and general emergency
      services should consider anxiety disorders in the differential diagnosis of
      patients with somatic complaints but without a diagnosis of physical disorder.

PMID- 7627676
TI  - The library as a resource for decision making in mental health care.
AB  - OBJECTIVE: The study sought to determine whether mental health practitioners
      decided to make changes in specific areas of patient or client care as a result
      of information obtained from library literature searches. METHODS: A ten-question
      survey was distributed to 350 mental health professionals who had requested at
      least one computerized literature search from a library affiliated with a state
      institute of mental health during an eight-month period. RESULTS: A total of 70.5
      percent of survey respondents made one or more changes in their approach to
      patient or client care after reviewing the information obtained through the
      search. CONCLUSIONS: Access to the wide range of research and experience embodied
      in the published literature is a valuable adjunct to the mental health
      professional's training and personal experience.

PMID- 7627677
TI  - New York State Community Mental Health Reinvestment Act.
AB  - In an era of scarce resources, public mental health systems have been struggling
      to develop comprehensive community-based treatment and rehabilitation systems for
      persons with mental illnesses. In New York State the Community Mental Health
      Reinvestment Act, signed into law in December 1993, establishing the state
      government's commitment over a five-year period to provide substantial new
      resources to fund the development of community services. The basic principle
      behind the legislation, the most significant reform in the state's mental health
      care financing in decades, is that funds saved from downsizing the state hospital
      system through closures and census reductions must be "reinvested" to create more
      community-based services. The authors describe the political processes leading to
      the act's passage, the obstacles overcome by legislative negotiators, the act's
      provisions, and some implementation issues. Although the act has received some
      criticism, it appears to be favorably regarded by mental health advocates,
      recipients, providers, and administrators.

PMID- 7627678
TI  - Evaluating the Johnson Foundation Program on Chronic Mental Illness. Interview by
      John A. Talbott.

PMID- 7627679
TI  - The needs and resources assessment interview for severely mentally ill adults.
AB  - The authors report an analysis of the reliability and validity of the Needs and
      Resources Assessment, an interview instrument that measures patients' needs and
      resources in 13 domains of functioning and rates patients' overall satisfaction
      with each domain and the importance of each need. Internal consistency of the
      instrument's four subscales-- needs, resources, satisfaction, and importance-
      ranged from .66 to .81, and test-retest reliability of the instrument ranged from
      .71 to .86. The subscales showed significant correlations with independent scales
      measuring size of the patient's support network, quality of life, and depressive
      symptoms. The Needs and Resources Assessment may be useful for prioritizing a
      patient's needs in developing an intervention plan in rehabilitation settings.

PMID- 7627680
TI  - Use of state hospital staff to provide training for staff of community
      residential facilities.
AB  - State hospital staff and other hospital resources in a region of Washington State
      were used to train staff of community residential facilities in the care of
      persons with serious mental illness. Forty-six staff members from 17 community
      facilities received week-long training in the program's first year. Participants
      expressed a high level of satisfaction with the program, and facility
      administrators indicated that it had a positive impact on the overall quality of
      services in their facility. The annual staff turnover rate among participants was
      dramatically lower than among other staff in the community facilities.

PMID- 7627681
TI  - Psychiatric symptoms and work performance among persons with severe mental
      illness.
AB  - The study examined the relationship between psychiatric symptoms and work
      performance for 61 subjects with a DSM-III-R diagnosis of schizophrenia or
      schizoaffective disorder who participated in a work rehabilitation program.
      Symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) to
      predict performance on the Work Personality Profile at three and 13 weeks of the
      program. Twenty-seven percent of the variance in work performance measures could
      be explained by symptom components measured by the PANSS, including the
      cognitive, negative, and hostility components, but the positive component did not
      predict work performance. Ratings of symptoms done concurrently with ratings of
      work performance were more powerful predictors than ratings of symptoms done at
      three and 13 weeks before ratings of work performance.

PMID- 7627683
TI  - Medical and narrative approaches in psychiatry.
AB  - Using a case example, the authors contrast two different approaches to
      psychiatric assessment: the medical approach, in which the physician examines
      signs and symptoms and compares them with diagnostic criteria for various
      disorders, and the narrative approach, in which the clinician tries to understand
      symptoms as a part of a meaningful story and as understandable responses to
      external conditions. Both approaches make essential contributions to psychiatry.
      The current conflict between biological psychiatry and psychotherapeutic
      psychiatry can be seen as a result of reductionist polarization involving these
      opposite approaches. The reconciliation of these opposites may be vital for the
      survival of general psychiatry as a medical specialty.

PMID- 7627682
TI  - Opiate antagonists for recurrent self-injurious behavior in three mentally
      retarded adults.
AB  - Opiate antagonists have shown promise for treating a subset of self injurious
      patients. The authors report on the use of naltrexone with three mentally
      retarded adults who had long histories of self-injurious behavior and
      unsuccessful behavioral and drug treatments; for all three, the self- injurious
      behavior was substantially decreased. The authors have found a positive response
      for half the self-injurious patients for whom naltrexone has been tried. Before
      any drug therapy is initiated, environmental reinforcers of the behavior should
      be sought out and modified, and any reversible medical and psychiatric disorders
      should be treated.

PMID- 7627684
TI  - The two-class system.

PMID- 7627686
TI  - Computerized database makes information available on state mental health agency
      structure, services.

PMID- 7627685
TI  - Safer psychiatric facilities.

PMID- 7627687
TI  - President drops plan to give states control of advocacy program.

PMID- 7627688
TI  - Apo(a) phenotypes and Lp(a) concentrations in offspring of men with and without
      myocardial infarction. The EARS Study. European Atherosclerosis Research Study.
AB  - In the European Atherosclerosis Research Study, genetic and environmental markers
      of risk of premature coronary heart disease were compared in offspring of men
      with and without myocardial infarction before the age of 55 years. Cases were 682
      students with a paternal history of myocardial infarction, and control subjects
      were 1312 students without such a history. The students were enrolled in 14
      universities in five European regions (Finland, Great Britain, and northern,
      middle, and southern Europe). Lipoprotein(a) [Lp(a)] concentrations were skewed
      towards lower concentrations in both cases (median, 7.3 mg/dL; 95% confidence
      interval, 6.3 to 8.1 mg/dL) and control subjects (median, 6.6 mg/dL; 95%
      confidence interval, 6.1 to 7.2 mg/dL) (P = .37). Significantly more northern
      European male cases than control subjects had Lp(a) levels exceeding 30 mg/dL (P
      = .040), but this did not pertain to females (P = .29), and overall, there was no
      difference between cases (16.5%) and control subjects (15.5%) in the frequency of
      Lp(a) concentrations above 30 mg/dL (P = .63). As expected, there was a
      significant (P < .01) inverse relationship between apo(a) molecular size and
      Lp(a) concentration. In Great Britain there was a significant difference in
      phenotype distribution between cases and control subjects (P = .035), due mainly
      to a high frequency of the apo(a) S2 isoform in cases. A similar but
      statistically insignificant tendency was seen in northern Europeans. In the three
      other regions, however, the distribution of apo(a) phenotypes among cases and
      controls was similar, and in the study population overall, the distribution of
      apo(a) phenotypes did not differ significantly (P = .74) between cases and
      control subjects.

PMID- 7627689
TI  - Determinants of lipid levels among children with heterozygous familial
      hypercholesterolemia in Norway.
AB  - Three founder mutations have been discovered among individuals with familial
      hypercholesterolemia (FH) in Norway: FHElverum and FHSvartor, predicted to be
      null alleles, and FHC210G, predicted to disrupt the secondary structure of the
      ligand-binding domain. To clarify the effect of these and other mutations on
      lipid levels and parental history of premature cardiovascular disease, we
      examined 164 boys and girls ages 6 to 16 years with heterozygous FH. Among all
      children, serum cholesterol levels of the FH parent, percent body fat, pubertal
      stage, and serum cholesterol levels of the non-FH parent, but not apo E
      polymorphism, were significant determinants of LDL cholesterol levels in a
      stepwise multiple regression equation and explained 40% (95% confidence interval
      [Cl], 25% to 55%) of the variance in LDL cholesterol. Among boys, percent body
      fat, dietary sucrose, and apo E genotype determined 31% (95% CI, 14% to 49%) of
      the variance in triglyceride levels; whereas among girls, only percent body fat
      was associated with triglyceride levels. Percent body fat was not associated with
      LDL cholesterol or triglyceride levels in the FHC210G group. The children's and
      FH parents' lipid levels and premature cardiovascular disease among parents were
      similar among the null-allele and defective-protein groups and in those with an
      undetected mutation. These data confirm that the phenotypic expression of FH in
      childhood is influenced by modifiable lifestyle characteristics and by genetic
      factors other than the underlying mutation and raise the possibility that body
      fatness may interact with genotype in determining lipid levels.

PMID- 7627690
TI  - Severe familial HDL deficiency in French-Canadian kindreds. Clinical,
      biochemical, and molecular characterization.
AB  - A decreased level of HDL cholesterol (HDL-C) is the most common lipoprotein
      abnormality seen in people with premature coronary artery disease (CAD). In many
      cases, HDL-C reduction in patients with CAD may be the result of increased apo B
      containing lipoprotein production by the liver with secondary
      hypoalphalipoproteinemia. Primary hypoalphalipoproteinemia is seen in
      approximately 4% of people with CAD. We report findings in four subjects with
      severe familial HDL deficiency (HDL-C << 5th percentile for age and sex; 0.08 to
      0.38 mmol/L) in three French-Canadian kindreds with autosomal codominant
      inheritance. By inclusion criteria, all four subjects had normal fasting
      triglycerides and none were diabetic. HDL particle size by gradient gel
      electrophoresis revealed small HDL particles (estimated Stokes' diameter, 8.14 to
      8.30 nm). Apo AI analysis by polyacrylamide gel electrophoresis and use of
      isoelectrofocusing gels in affected subjects revealed normal molecular weight
      (28.3 kD) and normal isoelectrofocusing point but a relative increase in
      proapoliprotein AI, with near-normal levels of proapolipoprotein AI in plasma,
      suggesting normal secretion of apo AI. Quantitative Southern blot analysis of the
      apo AI-CIII-AIV gene cluster reveals no gene rearrangements or allele deletion.
      Haplotypes of the apo AI gene, determined by use of the restriction enzymes Pst
      I, Xmn I, and Sst I and of the apo AII gene by use of the enzyme Msp I, did not
      reveal segregation of the low HDL-C trait with either the apo AI or the AII gene.
      Sequence analysis of the promoter region of the apo AI gene reveals
      heterozygosity for guanine-to-adenine substitution at position 76 in two kindreds
      with no evidence of segregation with the low HDL trait. None of the patients had
      mutations of the lipoprotein lipase gene common in subjects of French-Canadian
      descent. Haplotype analysis of the lipoprotein lipase gene did not show
      segregation with the low HDL trait. Plasma lecithin: cholesterol acyltransferase
      (LCAT) activity was found to be within normal levels in affected subjects and in
      nonaffected first-degree relatives. None of the affected subjects had clinical
      manifestations of Tangier disease. Two of the four cases examined, both men, had
      severe CAD and had undergone revascularization procedures. The third is a younger
      brother of one of these probands and the fourth is a 30-year-old woman, and both
      were free of clinical CAD. However, in none of the families did the low HDL trait
      unequivocally cosegregate with CAD.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7627691
TI  - Independent mutations at codon 3500 of the apolipoprotein B gene are associated
      with hyperlipidemia.
AB  - The apoB arginine-to glutamine change at codon 3500 has become established as a
      cause of failure of binding of the LDL particle to its receptor and the
      consequent hypercholesterolemia of familial defective apoB 100. A search for
      further similar mutations was undertaken by systematic screening of a candidate
      region of the apoB gene from individuals with hypercholesterolemia. Polymerase
      chain reaction and denaturing gradient gel electrophoresis were used. We describe
      two families in which a different mutation in the codon 3500 causes an arginine
      to-tryptophan substitution. Most adults in these families who have this mutation
      have hypercholesterolemia. LDL derived from all who have inherited the mutation
      is dysfunctional in that it allows only poor growth of an LDL cholesterol
      dependent cell line. We conclude that this arginine 3500 is essential to the
      function of apoB and that its loss and replacement by glutamine or tryptophan is
      responsible for the hypercholesterolemia of familial defective apoB 100.

PMID- 7627692
TI  - Polymorphisms of the apolipoprotein E gene and severity of coronary artery
      disease defined by angiography.
AB  - In a recent study, we could account for only about 50% of the variance in
      angiographically determined severity of coronary artery disease (CAD) with use of
      lipid and clinical variables as predictors. To explore the possible contribution
      of the apolipoprotein (apo) E polymorphisms to the severity of CAD (rather than
      to its occurrence), we studied 424 white patients aged 65 years or less
      consecutively referred for coronary angiography. Among the 304 male and 120
      female patients, there were 110 with no significant CAD and 118 with one, 96 with
      two, and 100 with three significantly diseased major coronary arteries (> 50%
      luminal obstruction). The allele frequencies were 0.068 for E2, 0.759 for E3, and
      0.172 for E4. The E2 frequency was slightly lower and E4 higher than the
      frequencies reported for healthy white populations (E2: 0.072 to 0.130; E4: 0.136
      to 0.160). There was a clear association between the apo E genotype and the
      number of significantly diseased vessels (regression coefficient = .12, P =
      .008). The frequency of the E4 allele increased linearly with the increase in CAD
      severity in both sexes (for none, one, two, and three significantly diseased
      vessels; female patients: 0.136, 0.161, 0.200, and 0.324; male patients: 0.136,
      0.167, 0.132, and 0.229, respectively, P < .01). The frequencies of the E2
      allele, on the other hand, decreased with increasing severity (for none, one,
      two, and three significantly diseased vessels; female patients: 0.091, 0.018,
      0.050, and 0.029; male patients: 0.073, 0.089, 0.072, and 0.054, respectively, P
      < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7627693
TI  - Dose-response relationships of serum lipid measurements with the extent of
      coronary stenosis. Strong, independent, and comprehensive. ECAT Angina Pectoris
      Study Group.
AB  - Serum lipids, lipoproteins, and more recently apolipoproteins and lipoprotein(a)
      [Lp(a)] have been shown to be independent risk factors for coronary vessel
      disease and its prognosis. However, the relationships between serum lipid levels
      and the extent of coronary artery disease (CAD) have not been consistently shown.
      Twenty-five hundred male and female patients with suspected angina pectoris were
      recruited from 18 European medical centers. The independent relations of total
      cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, apo A-I and B, and
      Lp(a) with the presence and extent of CAD, as assessed by coronary angiography,
      were investigated. All of the lipid measures showed strong relations P < .0001)
      with the presence of CAD, defined by the existence of at least one > or = 50%
      coronary vessel stenosis. Total cholesterol, LDL cholesterol, apo B,
      triglycerides, and Lp(a) were substantially higher and HDL cholesterol and apo A
      I lower in patients with CAD. The odds ratio of CAD, in the high-risk tertile of
      each lipid's distribution compared with the low-risk tertile, was in the range
      1.5 to 2.3. Each of total cholesterol (or LDL cholesterol or apo B), HDL
      cholesterol (or apo A), and Lp(a) had an independent effect in predicting the
      presence of CAD. In addition, all lipids showed a strong association (P = .0006
      for triglycerides, P < .0001 otherwise) with the extent of CAD as defined by the
      number of stenosed coronary vessels.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7627694
TI  - Predominance of large LDL and reduced HDL2 cholesterol in normolipidemic men with
      coronary artery disease.
AB  - Previous studies have indicated that a predominance of small, dense LDL particles
      is associated with coronary artery disease (CAD) risk. In the present study we
      examined the LDL peak particle diameter (determined by lipid-stained 2% to 16%
      gradient gel electrophoresis) in 92 normolipidemic men with CAD (total
      cholesterol < 200 mg/dL and triglyceride < 250 mg/dL) and 92 matched healthy
      controls. Plasma triglyceride, LDL cholesterol, and apo B levels were similar in
      subjects with CAD and in control subjects, whereas subjects with CAD had
      decreased HDL2 cholesterol levels (mean +/- SEM, 10 +/- 0.7 compared with 15 +/-
      0.7 mg/dL in control subjects; P < .0002). Mean LDL particle diameter (+/- SEM)
      was increased in the subjects with CAD compared with control subjects (26.8 +/-
      0.08 and 26.4 +/- 0.08 nm, respectively; P < .001). The association between large
      LDL size and CAD was significant (P < .0001) after adjustments were made for age,
      body mass index, HDL cholesterol levels, and VLDL cholesterol levels. An LDL
      particle size distribution characterized by a predominance of the largest of
      three classes of LDL particles (> 26.8 nm) was more prevalent among subjects with
      CAD (43%) than among control subjects (25%) (P < .002). Among subjects with this
      LDL size profile, subjects with CAD had significantly higher (P < .05) VLDL
      triglyceride, VLDL cholesterol, and VLDL apo B levels and significantly lower (P
      < .0001) HDL2 cholesterol levels than controls.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7627695
TI  - Lowering of HDL2b by probucol partly explains the failure of the drug to affect
      femoral atherosclerosis in subjects with hypercholesterolemia. A Probucol
      Quantitative Regression Swedish Trial (PQRST) Report.
AB  - The aim of the Probucol Quantitative Regression Swedish Trial (PQRST) (n = 303)
      was to investigate whether probucol (0.5 g BID) added to diet and cholestyramine
      (8 g BID) could retard progression or induce regression of femoral
      atherosclerosis in hypercholesterolemic (> 6.86 mmol/L) subjects. Probucol did
      not induce regression over the 3-year trial period as estimated by change in
      lumen volume on quantitative arteriography of a 20-cm segment of the femoral
      artery. In this report we studied in a representative subgroup (n = 72) whether
      the reduction in HDL concentrations induced by probucol could explain the failure
      of the drug to be effective. We analyzed the effects of treatment on HDL particle
      size subclasses. Probucol lowered the relative level of HDL2b, comprising the
      largest HDL particles, by 53% and the protein concentration of HDL2b by 67%. The
      protein reduction in HDL was mainly confined to the apolipoprotein A-I moiety.
      The change in lumen volume correlated significantly with change in HDL, ie, HDL
      cholesterol (r = .34, P < .01), HDL2 cholesterol (r = .37, P < .01), HDL2b
      protein (r = .44, P < .001), and the relative HDL2b value (r = .51, P < .001).
      The corresponding values for relative HDL2b, distribution calculated on the
      active (n = 35) and placebo (n = 37) groups separately were also significant (r =
      .39 and .32, respectively; both P < .05). The correlation between drug-induced
      change in the relative HDL2b concentration and change in atherosclerosis was
      independent of the alteration in triglyceride concentration and could not be
      explained by treatment interaction.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7627696
TI  - Probucol treatment decreases serum concentrations of diet-derived antioxidants.
AB  - The effect of probucol, which is both a cholesterol-lowering drug and an
      antioxidant, on the serum concentrations of diet-derived antioxidants vitamin E,
      beta-carotene, lycopene, and vitamin A was studied in 303 hypercholesterolemic
      subjects. In a 3-year, double-blind, randomized trial we investigated to
      determine whether combined treatment with diet, cholestyramine, and probucol
      could reduce the progression of femoral atherosclerosis. Serum and lipoprotein
      antioxidant levels were measured by reverse-phase high-performance liquid
      chromatography. Cholestyramine significantly lowered serum concentrations of
      vitamin E by 7%, beta-carotene by 40%, and lycopene by 30% (all P < .001) due to
      impairment of gastrointestinal absorption and to serum cholesterol lowering.
      Probucol reduced serum vitamin E by 14% (P < .001) secondary to cholesterol and
      triglyceride lowering. The carotenoids were reduced by probucol by 30% to 40% (P
      < .001) most probably due to reductions in lipoprotein particle size and to
      competition with these substances for incorporation into VLDL during its assembly
      in the liver. This study shows that the use of a lipid-soluble antioxidant and
      cholesterol-lowering drug may have unfavorable effects on blood levels of diet
      derived antioxidants.

PMID- 7627697
TI  - Effects of different phenotypes of hyperlipoproteinemia and of treatment with
      fibric acid derivatives on the rates of cholesterol 7 alpha-hydroxylation in
      humans.
AB  - Little is known about the relationships between hyperlipidemia and bile acid
      metabolism. However, hypolipidemic treatment with fibric acid derivatives has
      been shown to increase biliary cholesterol secretion, presumably by reducing bile
      acid synthesis. To clarify such relationships, we investigated the effects of
      different hyperlipoproteinemic conditions and of treatment with fibric acid
      derivatives on the rates of cholesterol 7 alpha-hydroxylation (the limiting step
      of bile acid synthesis) in humans. We studied 10 patients (aged 36 to 68 years)
      with lipoprotein phenotype IIa and with a clinical diagnosis of heterozygous
      familial hypercholesterolemia, a condition of reduced activity of LDL receptors,
      and 11 patients (aged 48 to 70 years) with lipoprotein phenotype IIb or IV and
      clinical diagnosis of familial combined hyperlipidemia, a condition probably
      related to increased hepatic lipoprotein synthesis. Cholesterol 7 alpha
      hydroxylation rates were assayed in vivo by tritium release assay after an
      intravenous injection of [7 alpha-3H]cholesterol. The results were compared by
      ANOVA to the values obtained in a group of 28 normolipidemic patients (aged 34 to
      83 years), with age as the covariate. Six patients were also studied after
      treatment with gemfibrozil (900 to 1200 mg/d for 6 to 8 weeks) and 5 patients
      were studied after treatment with bezafibrate (400 mg/d for 6 to 8 weeks).
      Hydroxylation rates were 0.82 +/- 0.22 mmol/d in the familial
      hypercholesterolemia group and 1.30 +/- 0.47 mmol/d in the familial combined
      hyperlipidemia group (P < .05 between the two groups and between patients with
      familial combined hyperlipidemia and control subjects; P = NS between patients
      with familial hypercholesterolemia and control subjects, as determined by
      ANOVA).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7627698
TI  - Body fat distribution is a determinant of the high-density lipoprotein response
      to dietary fat and cholesterol in women.
AB  - We have conducted a dietary trial that addressed the factors influencing the
      variability in plasma lipids in response to dietary fat and cholesterol with a
      focus on the effects of gender and body fat distribution. Sixty-seven women and
      53 men were selected so that overall men and women had a similar mean age, LDL
      cholesterol, and body mass index. After a 2-week low-fat period subjects were
      given two liquid supplements for 3 weeks each, one that contained 31 to 40 g fat
      and 650 to 845 mg cholesterol, and one that was fat free. Measurements included
      plasma lipids and lipoproteins, glucose, insulin, hepatic triglyceride lipase
      activity, apolipoprotein E polymorphism, and three indexes of body fat (body mass
      index, waist girth, and waist-hip ratio). In response to dietary fat and
      cholesterol supplementation only the changes in HDL cholesterol, especially in
      HDL2, differed between the sexes. Although on univariate analysis lipoprotein
      changes were predicted by baseline lipoprotein levels, body mass index, waist
      girth, waist-hip ratio, hepatic triglyceride lipase activity, and insulin,
      multiple regression showed only waist-hip ratio to predict changes in HDL2
      cholesterol in women and body mass index and baseline HDL2 cholesterol in men.
      Changes in LDL were predicted by baseline LDL cholesterol in women and
      apolipoprotein E phenotype and age in men. These studies explain much of the
      variability that individuals show in lipoprotein changes, especially in the more
      desirable changes in cholesterol transport in HDL2, in response to eating
      saturated fat and cholesterol.

PMID- 7627699
TI  - Efficacy of a National Cholesterol Education Program Step 2 diet in
      normolipidemic and hypercholesterolemic middle-aged and elderly men and women.
AB  - We tested the effects of a National Cholesterol Education Program (NCEP) Step 2
      diet (30% of calories or less as total fat, less than 7% saturated fat, and less
      than 200 mg cholesterol per day) on plasma lipid levels in normocholesterolemic
      and hypercholesterolemic middle-aged and elderly men and women. Thirty-two
      subjects were studied. Eight normolipidemic subjects (6 men and 2 women, mean age
      56 +/- 13 years) with LDL cholesterol levels of less than 4.14 mmol/L (160 mg/dL)
      were given a baseline diet similar in composition to the diet currently consumed
      in the United States (35% of calories as total fat and 14% as saturated fat, with
      147 mg cholesterol per 1000 kcal) for 6 weeks. Subjects were then placed on an
      NCEP Step 2 diet (26% total fat, 4% saturated fat, 45 mg cholesterol per 1000
      kcal) for 24 weeks. In addition, 24 subjects (12 men and 12 women, mean age 62 +/
      12 years) with moderate hypercholesterolemia (LDL cholesterol levels of 4.14
      mmol/L or above) were given a baseline diet for 6 weeks and then the NCEP Step 2
      diet for 6 weeks. Energy intakes were adjusted to keep body weight constant
      throughout the study. In both normolipidemic and hypercholesterolemic subjects,
      consumption of the NCEP Step 2 diet was associated with significant changes in
      levels of total cholesterol (-20% and -16%, respectively), LDL cholesterol (-21%
      and -18%, respectively), and HDL cholesterol (-16% and -15%,
      respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7627700
TI  - Lipoprotein lipase mass and activity in plasma and their increase after heparin
      are separate parameters with different relations to plasma lipoproteins.
AB  - Lipoprotein lipase (LPL) activity and mass in plasma and their increase after
      heparin administration were measured in 61 men who had suffered myocardial
      infarction before the age of 45 years and in 69 population-based age- and sex
      matched control subjects without coronary heart disease to study the relations
      between these parameters in plasma and their correlations with plasma
      lipoproteins in subjects with a wide range of lipoprotein and LPL levels. There
      was a relatively large amount of LPL protein compared with LPL activity in
      preheparin plasma, indicating that the majority of circulating LPL is
      catalytically inactive. LPL mass and activity in postheparin plasma (postheparin
      minus preheparin values) were highly correlated, and the calculated mean specific
      activity (0.35 mU/ng) was in the range expected for catalytically active LPL.
      Hence, heparin releases mainly active LPL. The four LPL parameters (mass and
      activity in plasma and their increase after heparin administration) were not
      related to each other, except for postheparin plasma LPL mass and activity, and
      they showed different correlations with plasma lipoprotein lipid concentrations.
      There was a strong positive correlation between LPL mass in preheparin plasma and
      the HDL cholesterol level as well as weak negative relations to VLDL triglyceride
      and cholesterol concentrations in the patients. In contrast, preheparin LPL
      activity showed no correlation with the HDL cholesterol level but weak positive
      relations to VLDL triglyceride and cholesterol concentrations in the control
      subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7627701
TI  - Determinants of fibrin D-dimer in the Edinburgh Artery Study.
AB  - There is growing evidence that fibrin D-dimer is associated with coronary and
      peripheral atherosclerosis. Using data from the Edinburgh Artery Study, we
      examined the distribution of fibrin D-dimer in 1592 men and women 55 to 74 years
      old and assessed its relationship with a range of cardiovascular risk factors.
      Fibrin D-dimer levels were higher in women than in men (P < or = .05) and
      increased with age (P < or = .001). Current cigarette smokers had higher levels
      than ex-smokers, who, in turn, had higher levels than those who had never smoked.
      On multiple regression analyses with age and plasma fibrinogen as covariates,
      only lifetime smoking in men and systolic blood pressure in women were
      independent predictors of fibrin D-dimer levels. Since fibrin D-dimer does not
      appear to be independently related to many of the common cardiovascular risk
      factors, it may be a useful index of the thrombotic contribution to arterial
      disease.

PMID- 7627702
TI  - Active site-blocked factors VIIa and IXa differentially inhibit fibrin formation
      in a human ex vivo thrombosis model.
AB  - The role of tissue factor/factor VIIa (FVIIa) and factor VIIIa/factor IXa
      (FVIIIa/FIXa) complexes in thrombus formation was examined in a human ex vivo
      blood flow system by use of active site-blocked FVIIa (FVIIai) and FIXa (FIXai)
      as selective inhibitors. Blood was drawn directly from the veins of volunteers
      into a mixing device where FVIIai and FIXai were mixed with flowing blood. The
      blood then entered parallel-plate chambers containing coverslips coated with
      human fibrillar collagen or tissue factor-expressing cell layers of tumor
      necrosis factor-alpha-stimulated human endothelial cells, human smooth muscle
      cells, and J82 cells. Exposure of stimulated endothelial cells to blood flowing
      at a venous shear rate of 65/s led to fibrin deposition, which was inhibited by
      infusion of FVIIai (IC50, 3 nmol/L), as quantified by micro-densitometry of
      fibrin-stained coverslips. Whereas FIXai (600 nmol/L) was only a weak inhibitor,
      FVIIai (60 nmol/L) reduced fibrinopeptide A (FPA) plasma levels from 504 +/- 79
      to 171 +/- 27 ng/mL and concomitantly inhibited platelet thrombus deposition.
      Similarly, experiments with smooth muscle cells and J82 cells showed that FVIIai
      but not FIXai efficiently reduced FPA levels. Conversely, with tissue factor-free
      collagen, ,hich induces platelet-dependent fibrin formation, infusion of FIXai
      but not of FVIIai inhibited fibrin deposition (IC50, 8 nmol/L) and reduced FPA
      levels from 55 +/- 8 to 9 +/- 5 ng/mL. However, FIXai did not affect the number
      of platelet thrombi deposited on collagen.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7627703
TI  - Evaluation of factor XIa-alpha 1-antitrypsin in plasma, a contact phase-activated
      coagulation factor-inhibitor complex, in patients with coronary artery disease.
AB  - Excess activated factor XI (FXIa) in plasma indicates increased activation during
      the contact phase of blood coagulation. To investigate the relationship between
      such elevations and coronary atherosclerosis, we examined FXIa values in patients
      with coronary artery disease (CAD) by an enzyme-linked immunosorbent assay method
      that we developed that detects FXIa in plasma samples as an FXIa-alpha 1
      antitrypsin complex (FXIa-alpha 1AT). The presence and extent of CAD were
      documented by coronary angiography and assessed by a recently developed scoring
      system for semiquantitative estimation of coronary atherosclerosis. Plasma FXIa
      alpha 1AT levels were significantly increased in patients with angiographically
      proven CAD (13.9 +/- 3.0 micrograms/L, n = 42) compared with age-matched, healthy
      control subjects (11.9 +/- 1.7 micrograms/L, n = 20) as well as patients with
      angiographically normal coronary arteries (12.0 +/- 2.3 micrograms/L, n = 25).
      Moreover, in the total patient population, the FXIa-alpha 1AT level was related
      to the number of significant coronary artery stenoses as well as to the total
      coronary score. FXIa-alpha 1AT showed a positive correlation with thrombin
      antithrombin III complex, fibrinogen, and Lp(a) and an inverse correlation with
      apo A-I, as determined by multi-variate analysis. Our studies provide evidence
      that increased activation of the contact pathway occurs in patients with CAD and
      is related to the severity of the disease. Although it is unknown whether this
      abnormality is the cause or the result of the vascular lesion, it may be
      important for progression of the underlying atherosclerosis or for propagation of
      the atherosclerotic process itself.

PMID- 7627704
TI  - Activation of tissue factor-induced coagulation and endothelial cell dysfunction
      in non-insulin-dependent diabetic patients with microalbuminuria.
AB  - We studied the relationships between albuminuria, tissue factor-induced
      coagulation, and endothelial cell dysfunction in 67 patients with non-insulin
      dependent diabetes mellitus (NIDDM) who were divided into three groups on the
      basis of their urinary albumin excretion rate (AER). To assess the early phase of
      tissue factor-induced coagulation, activated factor VII (FVIIa) levels in plasma
      were measured by a direct fluorogenic assay. As markers of endothelial cell
      dysfunction, levels of von Willebrand factor (vWF), tissue-type plasminogen
      activator-plasminogen activator inhibitor-1 (TPA-PAI-1) complex, PAI-1, and
      tissue factor pathway inhibitor (TFPI) were measured. FVIIa levels were increased
      in normoalbuminuric NIDDM patients (AER < 15 micrograms/min) when compared with
      normal control subjects. This FVIIa increase was accompanied by an increase in
      thrombin-antithrombin III complex (TAT) levels, indicating increased activation
      of coagulation even in normoalbuminuric patients. In NIDDM patients with
      microalbuminuria (AER = 15-200 micrograms/min), the FVIIa level, the FVIIa-FVII
      antigen (Ag) ratio (an indicator of activation of FVII zymogen to FVIIa), and the
      TAT level were further increased. This group also had higher levels of
      endothelial cell-derived factors (vWF, TPA-PAI-1 complex, and PAI-1) than the
      control group. The levels of endothelial cell-derived factors (including TFPI)
      were highest in the NIDDM patients with overt albuminuria (AER > 200
      micrograms/min). In all 67 diabetic patients, AER showed a strong positive
      correlation with FVIIa (r = .574, P < .0001) and a weakly but still significant
      correlation with FVIIa-FVII:Ag (r = .365, P = .01), vWF (r = .315, P < .01), and
      TAT (r = .323, P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7627705
TI  - Tissue factor pathway inhibitor activity associated with LDL is inactivated by
      cell- and copper-mediated oxidation.
AB  - Human plasma contains a multivalent, Kunitz-type proteinase inhibitor termed
      tissue factor pathway inhibitor (TFPI), which is a specific inhibitor of the
      action of the factor VII(a)-tissue factor complex in coagulation. A major
      fraction of plasma TFPI is transported in association with LDL. Because LDL may
      undergo oxidation in the arterial wall during atherogenesis, we examined the
      effect of copper- and cell-mediated oxidative modification on TFPI activity
      associated with LDL. Oxidation mediated by copper ions resulted in a significant
      inactivation of LDL-associated TFPI (60% to 72% at 24 hours with 2.5 mumol/l
      CuCl2). The inactivation of TFPI was strongly negatively correlated with both an
      increase in the net electrical charge of LDL (r = -.80, P < or = .0001) and with
      the production of thiobarbituric acid-reactive substances (r = -.78, P < or =
      .0001) and lipid peroxides (r = -.80, P < or = .0001). Cell-mediated oxidation,
      involving incubation of LDL for 48 hours with either monocyte-like THP1 cells or
      human monocytes in Ham's F-10 medium, effected a significant decrease (64% and
      75%, respectively) in LDL-associated TFPI activity. By contrast, prolonged
      exposure of LDL to purified soybean lipoxygenase (5000 U/mL) was less effective
      in inactivating TFPI (47% reduction after incubation for 72 hours at 37 degrees
      C). We subsequently investigated the mechanism(s) that may underlie such
      inactivation. Oxidation of LDL is accompanied by the generation of various
      aldehydes, including malondialdehyde and 4-hydroxynonenal. Chemical modification
      with these aldehydes revealed a significant inverse correlation between the
      progressive loss of TFPI activity and both the increase in net electrical charge
      (r = -.90, P < or = .0001) and the derivatization of free amino acid residues of
      LDL (r = -.90, P < or = .0001). Specific chemical modification of lysine amino
      groups by acetylation similarly led to inactivation of LDL-associated TFPI
      activity. TFPI activity was almost totally abolished (< 1.4%) when the TNBS
      reactivities of acetylated LDL, malondialdehyde-modified LDL, and 4
      hydroxynonenal-modified LDL were 31%, 21%, and 43% that of native LDL,
      respectively. Our data demonstrate that expression of LDL-associated
      anticoagulant activity is markedly decreased as a consequence of the oxidative
      process, and suggest that the progressive aldehydic derivatization of apo B of
      LDL, and of the associated TFPI protein, may contribute to this phenomenon.
      Because tissue factor is overexpressed in the atheromatous plaque, it may exert a
      marked local procoagulant effect.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7627706
TI  - Mildly oxidized LDL induces platelet aggregation through activation of
      phospholipase A2.
AB  - Native LDL and LDL oxidized under various conditions were compared in terms of
      their ability to activate platelets. Native LDL did not induce platelet shape
      change or aggregation, even at high concentrations (2 mg protein/mL). LDL was
      mildly oxidized with either CuSO4 (mox-LDL) or 3-(N-morpholino)sydnonimine (SIN-1
      LDL). Analysis of mox-LDL and SIN-1-LDL showed a small increase of dienes (E234nm
      from 0.28 +/- 0.04 to 0.55 +/- 0.09, mean +/- SD) and thiobarbituric acid
      reactive substance (from 0 to 10.6 +/- 1.5 nmol/mg, mean +/- SEM), no change in
      apo B electrophoretic mobility, and a minor (12% to 30%) decrease in
      polyunsaturated fatty acid content. Interestingly, this small oxidative
      modification of LDL dramatically changed its effect on platelets. Irreversible
      aggregation and secretion were induced by a threshold concentration of 0.4 mg
      protein/mL. In contrast, LDL thoroughly oxidized with CuSO4 (ox-LDL) did not
      aggregate platelets. Although mox-LDL was depleted in antioxidants (alpha- and
      gamma-tocopherol, alpha- and beta-carotene, and other carotenoids), incubation of
      mox-LDL with exogenous alpha-tocopherol did not reverse its ability to induce
      platelet aggregation and secretion. Preincubation of platelets with the
      cyclooxygenase inhibitor aspirin or the phospholipase A2 inhibitors
      trifluoperazine, quinacrine, 4-bromophenacyl bromide, and propranolol completely
      prevented platelet aggregation and secretion caused by mox-LDL or SIN-1-LDL.
      These results indicate that mildly oxidized LDL activates platelets through a
      phospholipase A2/cyclooxygenase-dependent pathway. The complete inhibition of mox
      LDL-induced platelet aggregation by aspirin could contribute to its beneficial
      effect in cardiovascular disease.

PMID- 7627707
TI  - In situ localization and quantification of mRNA for 92-kD type IV collagenase and
      its inhibitor in aneurysmal, occlusive, and normal aorta.
AB  - Ninety-two-kilodalton type IV collagenase (MMP-9) is present in aortic aneurysms
      and may be important to the pathogenesis of this disease. Alteration in
      expression of MMP-9 or its inhibitor, the tissue inhibitor of metalloproteinase
      type 1 (TIMP-1), could increase degradation of extracellular matrix and lead to
      aneurysm formation. The purpose of this study was (1) to measure tissue levels of
      MMP-9 and TIMP-1 mRNA in aneurysmal (AAA), atherosclerotic occlusive (AOD), and
      normal (NL) human infrarenal aorta; (2) to test for their expression by cultured
      AAA and NL vascular smooth muscle cells (VSMCs); and (3) to locate in situ the
      cells responsible for mRNA production within AAA, AOD, and NL aortic wall. Total
      RNA extracted from AAA (n = 8), AOD (n = 8), and NL (n = 7) tissue was subjected
      to Northern analysis. Signals for MMP-9 and TIMP-1 were normalized to alpha
      tubulin. Mean values +/- SEM were compared by ANOVA. NL and AAA VSMCs were
      cultured, passaged, and grown to confluence before RNA extraction and Northern
      analysis. In situ hybridization with digoxigenin-labeled RNA probes localized
      cells responsible for MMP-9 and TIMP-1 mRNA expression within sections of AAA (n
      = 5), AOD (n = 2), and NL (n = 2) aorta. MMP-9 mRNA levels were significantly
      greater in AAA (0.855 +/- 0.180) than NL (0.046 +/- 0.23) (P < .02), but
      differences between AOD (0.406 +/- 0.196) and AAA or AOD and NL were not
      significant.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7627708
TI  - Inflammation and matrix metalloproteinases in the enlarging abdominal aortic
      aneurysm.
AB  - The risk of rupture of an abdominal aortic aneurysm increases with aortic
      diameter. To obtain insight into the pathological processes associated with the
      vascular remodeling that accompanies aortic dilatation, we compared the
      histological features and the activity of matrix metalloproteinases (MMPs) in
      biopsies from 21 small (4.0 to 5.5 cm in diameter) and 45 larger abdominal aortic
      aneurysms. The histological feature most clearly associated with enlarging
      aneurysm diameter was a higher density of inflammatory cells in the adventitia, P
      = .018. This inflammation was nonspecific, principally macrophages and B
      lymphocytes. Fibrosis of the adventitia provided compensatory thickening of the
      aortic wall as the aneurysm diameter increased. A combination of zymography and
      immunoblotting identified gelatinase A (MMP-2) as the principal metallogelatinase
      in small aneurysms, whereas zymography indicated an increasing activity of
      gelatinase B (MMP-9) in large aneurysms. Homogenates prepared from both small and
      large aneurysms had similar total activity against gelatin or type IV collagen.
      However, the concentration of gelatinase A, determined by immunoassay, was
      highest for small aneurysms: median concentrations, 385, 244, and 166 ng/mg
      protein for small aneurysms, large aneurysms, and atherosclerotic aorta,
      respectively. Immunolocalization studies indicated that gelatinase A was
      concentrated along fibrous tissue of both the acellular media and the
      atherosclerotic plaque. The recruitment of inflammatory cells into the
      adventitia, with subsequent elaboration of metalloproteinases, including
      gelatinase B, may contribute to the rapid growth and rupture of larger aneurysms.

PMID- 7627709
TI  - Development and progression of atherosclerosis in aorta from heterozygous and
      homozygous WHHL rabbits. Effects of simvastatin treatment.
AB  - This study was conducted to define progression of atherosclerosis in both
      homozygous and heterozygous Watanabe heritable hyperlipidemic (WHHL) rabbits and
      to investigate the ability of the HMG CoA reductase inhibitor simvastatin to
      attenuate progression of the disease. We examined contractile responses to
      phenylephrine and endothelium-dependent relaxation in response to carbachol in
      thoracic aorta at 3, 6, 9, and 12 months in control New Zealand White (NZW)
      rabbits, homozygous WHHL rabbits, and heterozygous WHHL rabbits. Homozygous and
      heterozygous rabbits were treated with simvastatin (10 mg/kg per day) from 3 to 6
      months and from 9 to 12 months of age. Simvastatin significantly reduced serum
      cholesterol levels in young heterozygotes, with a nonsignificant trend toward a
      reduction in older heterozygotes. In homozygotes, no significant fall was
      observed. Contractile function declined progressively with age in all groups-
      most in homozygotes and least in NZW rabbits. Relaxation was unaffected by age in
      NZW rabbits; relaxation declined in the heterozygotes and declined to a greater
      extent in homozygotes. Simvastatin retarded the loss of function in the young
      heterozygotes. Similar trends were observed in young homozygotes and older
      heterozygotes, with no effect in older homozygotes. Histological studies revealed
      the progressive development of early atherosclerosis in heterozygotes, and more
      advanced atherosclerosis was observed in homozygotes. Simvastatin did not inhibit
      development of atheroma. A correlation was observed between vascular function and
      structure. However, functional changes preceded the development of atheroma. In
      addition, we have demonstrated that simvastatin can help to reduce the loss of
      vascular function associated with the progression of atherosclerosis in the
      heterozygous WHHL rabbit.

PMID- 7627710
TI  - Mibefradil prevents neointima formation after vascular injury in rats. Possible
      role of the blockade of the T-type voltage-operated calcium channel.
AB  - Mibefradil is a novel calcium antagonist that is selective for the T-type voltage
      operated calcium channel rather than the L type. Because T-type calcium channels
      are present on rapidly proliferating cells and mediate the increase of
      intracellular calcium induced by some growth factors, such as platelet-derived
      growth factor, we hypothesized that the blockade of T channels could prevent the
      excessive smooth muscle cell proliferation that occurs in conditions such as
      vascular injury. To test this hypothesis, we evaluated in rats the effects of
      mibefradil (which blocks both L- and T-type channels) on neointima formation
      after vascular injury, and we compared them with those of equihypotensive doses
      of amlodipine and verapamil (which block only L-type channels). Mibefradil (30
      mg/kg) decreased the area of neointima formed 14 days after balloon injury by 54%
      (P < .001). In contrast, neither verapamil nor amlodipine had an effect despite a
      blood pressure reduction at least equal to that of mibefradil. The in vivo effect
      of mibefradil was indeed an inhibition of smooth muscle cell proliferation, as
      shown by thymidine incorporation experiments. This antiproliferative effect of
      mibefradil was also observed in vitro in smooth muscle cells stimulated by fetal
      calf serum. In this condition also, verapamil was ineffective. We conclude that
      in rats mibefradil has a potent antiproliferative effect on smooth muscle cells
      after vascular injury. This effect might be due to blockade of voltage-operated T
      channels.

PMID- 7627711
TI  - Immunosuppressive agents and endothelial repair. Prednisolone delays migration
      and cytoskeletal rearrangement in wounded porcine aortic monolayers.
AB  - Endothelial denudation at areas of predilection to atherosclerosis is balanced by
      an active repair process that may be inhibited under conditions of accelerated
      atherosclerosis. After cardiac transplantation, the accelerated atherosclerotic
      process that develops may be enhanced by immunosuppressive agents that have
      nonspecific effects on cell signaling, proliferation, and response to injury. To
      study subtle effects of cyclosporine A, azathioprine, and 6 alpha
      methylprednisolone on normal endothelial repair processes, confluent porcine
      endothelial monolayers were denuded in the presence of clinically relevant
      concentrations of these agents. The rate of endothelial wound repair was compared
      and the effects on cell spreading, proliferation, and the cytoskeleton assessed.
      6 alpha-Methylprednisolone at concentrations of 1.25 to 50 mumol/L was associated
      with a transient 30% to 60% inhibition of endothelial wound repair. This was
      associated with increased cell size at the wound edge and a delay in centrosomal
      reorientation toward the wound, without any effect on cell proliferation.
      Cyclosporine and azathioprine in clinically relevant concentrations did not
      affect endothelial repair. Thus, corticosteroids transiently inhibit endothelial
      cytoskeletal alterations that are important in endothelial repair after a
      denuding injury.

PMID- 7627712
TI  - Low atherosclerotic response of a strain of rabbits to diet-induced
      hypercholesterolemia.
AB  - In this report we describe the development of two rabbit strains, HAR (high
      atherosclerotic response) and LAR (low atherosclerotic response), and their
      propensities to develop atherosclerosis in the aorta despite similar levels of
      diet-induced hypercholesterolemia. Sixty-two randomly selected male New Zealand
      White rabbits were fed a cholesterol-enriched diet (0.5%) for 84 days and
      developed 57 +/- 25% sudanophilic lesions of the aortic surface; 12 rabbits
      showed a low atherosclerotic response (0% to 30% surface involvement), and 22
      rabbits showed a high atherosclerotic response (70% to 100% surface involvement).
      The offspring of rabbits with low atherosclerotic response were used for breeding
      the strain of rabbits resistant to atherosclerosis (LAR strain), while the
      offspring of rabbits with high atherosclerotic response were used for breeding
      the HAR strain. Controlled breeding was started after the 4th generation and
      performed for the subsequent 6 generations. Thus, in the LAR rabbits the lipid
      stainable surface area of aorta amounted to only 27 +/- 17% after 112 days of
      cholesterol feeding. On the other hand, in HAR rabbits, aortic surface
      involvement reached 85 +/- 25% after 112 days on the cholesterol-enriched diet.
      The measurements of surface area involvement were corroborated also by a
      significantly lower, chemically determined cholesterol content of the aorta in
      LAR rabbits. Plasma lipids and lipoproteins were determined at baseline, after 21
      and 42 days of cholesterol feeding, and at the time the animals were killed. The
      plasma cholesterol concentrations of cholesterol-fed HAR and LAR rabbits showed a
      13-fold increase after 21 days and a 21-fold increase after 84 days on the
      cholesterol diet.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7627713
TI  - Genetic differences of lipid metabolism in macrophages from C57BL/6J and C3H/HeN
      mice.
AB  - Cholesterol metabolism in macrophages from atherosclerosis-prone C57BL/6J mice
      was compared with that in macrophages from atherosclerosis-resistant C3H/HeN
      mice. Plasma total cholesterol levels of both types of mice were significantly
      increased, but HDL cholesterol level was increased only in C3H/HeN mice when a
      high-cholesterol diet (1% cholesterol) was fed for 5 weeks. After incubation of
      macrophages from male and female mice on the high-cholesterol diet with beta-VLDL
      for 24 hours, cholesterol content in macrophages from C57BL/6J was approximately
      1.5- to 2.0-fold higher than in those from C3H/HeN mice. [3H]Cholesterol oleate
      beta-VLDL incorporation into macrophages from C57BL/6J mice on the high
      cholesterol diet was greater than incorporation into those from C3H/HeN mice. The
      release of [3H]cholesterol from macrophages from C57BL/6J mice on the high
      cholesterol diet was one seventh that from macrophages from C57BL/6J mice on the
      basal diet or that from macrophages from C3H/HeN mice on the basal or high
      cholesterol diet. Acid cholesterol esterase activity was almost the same in
      macrophages from any group. Acyl CoA:cholesterol acyltransferase activity in
      macrophages from C57BL/6J mice on the high-cholesterol diet increased compared
      with that from macrophages from C57BL/6J mice on the normal diet. Neutral
      cholesterol esterase activity in macrophages from C57BL/6J mice was about half of
      that in macrophages from C3H/HeN mice independent of the type of diet. There were
      no sex differences in these metabolisms. Considered with our previous data, these
      results suggested that a high-cholesterol diet may cause metabolic changes to
      accumulate cholesterol ester in macrophages from C57BL/6J mice in accordance with
      genetic abnormalities.

PMID- 7627714
TI  - Inhibition of protein tyrosine kinase alters the effect of serum basic protein I
      on triacylglycerols and cholesterol differently in normal and hyperapoB
      fibroblasts.
AB  - We studied whether the stimulatory effect of human serum basic protein I (BP I)
      on the formation of cell triacylglycerols and cholesterol may be mediated through
      protein tyrosine kinase in normal fibroblasts, and whether there was a deficiency
      in such a process in cells from subjects with hyperapobetalipoproteinemia
      (hyperapoB). Genistein, a highly specific inhibitor of tyrosine kinase
      phosphorylation, was used as a probe. When BP I (428.0 nmol/L) alone was added to
      F-12 medium without genistein, the mean mass of cell triacylglycerols doubled in
      six normal cell lines from healthy subjects, an effect that was decreased by 50%
      in six cell lines from subjects with hyperapoB (P = .007). The addition of
      genistein with BP I to normal cells decreased the stimulation of triacylglycerol
      formation by BP I by about 50% (P = .008), whereas genistein had little effect in
      the BP I-treated hyperapoB cells. The effect of genistein on the stimulation of
      triglyceride and cholesterol production by BP I was shown to be both time and
      concentration (92.5 nmol/mL medium nadir) dependent. In normal fibroblasts. BP I
      stimulated the rate of incorporation of both [14C]acetate (P = .0001) and
      [3H]mevalonolactone (P = .002) into unesterified cholesterol, an effect that was
      markedly deficient in the hyperapoB cells (P = .0001 for [14C]acetate and P =
      .0002 for [3H]mevalonolactone). In normal but not hyper-apoB cells, genistein
      inhibited the significant stimulation by BP I of the rates of both [14C]acetate
      (P = .0001) and [3H]mevalonolactone (P = .04) incorporation into unesterified
      cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7627715
TI  - T lymphocytes affect smooth muscle cell phenotype and proliferation.
AB  - The effects of rabbit T lymphocytes on rabbit aortic smooth muscle cell (SMC)
      phenotype and proliferation were investigated in vitro. SMCs seeded at confluent
      density in primary culture had a volume fraction of myofilaments (Vvmyo) of 49.8
      +/- 2.6% after 3 days of culture, not significantly different from that of
      freshly dispersed cells (Vvmyo, 54.1 +/- 2.1%). Sister cultures of SMCs to which
      Concanavalin A-activated T lymphocytes or T lymphocyte-conditioned medium was
      added had significantly lower Vvmyo (35.5 +/- 2.2% and 31.6 +/- 2.3%,
      respectively) at the same time point. We have previously shown that a decrease in
      Vvmyo could be induced by the heparan sulfate-degrading activity of living
      macrophages and by commercial preparations of heparinase. While activated T
      lymphocytes also completely degraded heparan sulfate-rich 35S-labeled
      extracellular matrix (an effect inhibited by the addition of 10 micrograms/mL
      heparin), no heparanase-like activity was detected in T lymphocyte-conditioned
      medium, indicating that for this cell type SMC phenotypic change is induced by a
      different mechanism. Incubation of the T lymphocyte-derived cytokine interferon
      gamma (IFN-gamma) with freshly isolated rat SMCs caused a significant reduction
      in Vvmyo at day 2 in primary culture from 54.3 +/- 2.1% (control) to 35.4 +/-
      3.0%. Furthermore, a neutralizing antibody specific for IFN-gamma removed the
      effect of T lymphocytes and medium conditioned by them, thus positively
      identifying IFN-gamma as the T lymphocyte factor responsible for this activity. T
      lymphocyte-conditioned medium was mitogenic for passaged (low Vvmyo)
      SMCs.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7627716
TI  - Upregulation of connexin43 gap junctions during early stages of human coronary
      atherosclerosis.
AB  - Interactions between cells form the framework for understanding the pathogenesis
      of atherosclerosis, but little information is available on the role of direct
      intercellular communication via gap junctions in this process. To investigate gap
      junction expression in the pathogenesis of human atherosclerosis, lesions
      representing different stages of the disease were obtained from coronary arteries
      of hearts removed from patients undergoing cardiac transplantation. Twelve
      hearts, each providing 1 to 3 segments of artery, were used in the study.
      Sections were examined by confocal laser scanning microscopy after
      immunofluorescent labeling with a specific antibody against connexin43, the major
      gap-junctional protein of smooth muscle cells, to permit high-definition
      visualization of immunolabeled gap junctions through the depth of the specimen.
      Double labeling using anti-connexin43 and cell type-specific antibodies
      demonstrated colocalization of gap junctions with smooth muscle cells but not
      with macrophages, a relationship confirmed by electron microscopy. Regions of
      intimal thickening and early atheromatous lesions showed markedly increased
      expression of connexin43 gap junctions between intimal smooth muscle cells
      compared with the undiseased vessels. This increase in gap junctions was most
      marked in regions of intimal thickening, semiquantitative analysis of the
      confocal digital images revealing a > 10-fold increase compared with the
      undiseased vessel. The quantity of labeled gap junctions in early atheromatous
      lesions, although higher than that of the undiseased vessel, was lower than that
      of intimal thickenings, and this trend toward reduced levels of gap junction
      immunolabeling with lesion progression continued, the value observed in the most
      advanced atheromatous lesions being lower than that of the undiseased vessel. As
      the quantity of gap junctions declined, their distribution became more patchy and
      the sizes of individual junctions larger. The results suggest that enhanced
      expression of gap junctions between smooth muscle cells may play a role in
      maintaining the synthetic phenotype during early growth of the atherosclerotic
      plaque.

PMID- 7627717
TI  - Functional properties of human vascular endothelial cadherin (7B4/cadherin-5), an
      endothelium-specific cadherin.
AB  - Human vascular endothelial cadherin (VE-cadherin, 7B4/cadherin-5) is an
      endothelial-specific cadherin localized at the intercellular junctions. To
      directly investigate the functional role of this molecule we cloned the full
      length cDNA from human endothelial cells and transfected its coding region into
      Chinese hamster ovary cells. The product of the transfected cDNA had the same
      molecular weight as the natural VE-cadherin in human endothelial cells, and
      reacted with several VE-cadherin mouse monoclonal antibodies. Furthermore, it
      selectively concentrated at intercellular junctions, where it codistributed with
      alpha-catenin. VE-cadherin conferred adhesive properties to transfected cells. It
      mediated homophilic, calcium-dependent aggregation and cell-to-cell adhesion. In
      addition, it decreased intercellular permeability to high-molecular weight
      molecules and reduced cell migration rate across a wounded area. Thus, VE
      cadherin may exert a relevant role in endothelial cell biology through control of
      the cohesion and organization of the intercellular junctions.

PMID- 7627718
TI  - Apolipoprotein B and E basic amino acid clusters influence low-density
      lipoprotein association with lipoprotein lipase anchored to the subendothelial
      matrix.
AB  - Lipoprotein accumulation in the subendothelial matrix is an important step in
      atherogenesis. We have previously shown that addition of lipoprotein lipase (LPL)
      markedly increased binding of apolipoprotein B (apoB)-containing lipoproteins to
      an endothelial cell-derived matrix, and this enhanced lipoprotein binding was
      inhibited by apoE. In the present studies we examined the role of various regions
      of apoB in the binding of LDL to LPL-containing endothelial cell matrix and the
      ability of various apoE domains to decrease lipoprotein retention. We studied
      three apoB epitope-specific monoclonal antibodies for their ability to block the
      binding of 125I-LDL to LPL-containing matrix. Of these, monoclonal antibody 4G3,
      which recognizes an arginine-containing epitope in apoB, was the most effective
      in reducing LDL binding. Chemical modification of LDL apoB lysines or arginines
      markedly reduced the ability of the lipoprotein to block the binding of 125I-LDL
      to LPL-containing matrix, suggesting that apoB positively charged amino acids are
      involved in the interaction. Furthermore, polyarginine or polylysine markedly
      decreased 125I-LDL binding to LPL-containing matrix, whereas polyleucine was
      ineffective. These data suggest that apoB positively charged regions are
      important in LDL binding. To explore the role of charge modifications on apoE by
      single arginine-cysteine interchanges, we examined the effects of the three major
      human apoE isoforms (apoE2, apoE3, and apoE4). ApoE3 was the most effective in
      decreasing 125I-LDL retention, followed by apoE4; apoE2 was the least effective.
      Similarly, apoE2-containing HDL was much less effective than apoE3-containing HDL
      in decreasing 125I-LDL retention.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7627719
TI  - Platelet-derived growth factor enhances Sp1 binding to the LDL receptor gene.
AB  - We have previously demonstrated that growth activation of quiescent cells
      enhances LDL receptor gene transcription and that the proximal 5' flanking region
      of the LDL receptor gene could transduce a platelet-derived growth factor (PDGF)
      response. This portion of the LDL receptor gene encompasses a previously
      characterized sterol response element and an adjacent Sp1 binding site. By use of
      mobility shift analyses we show that PDGF activation of quiescent cells enhances
      binding of Sp1 to the LDL receptor gene. Transfection analyses indicated that the
      Sp1 site, but not the sterol response element binding protein site, could confer
      PDGF responsiveness to a heterologous promoter in quiescent cells. Furthermore,
      cotransfection of an LDL receptor reporter gene (containing -141 to +35 bp of the
      LDL receptor gene promoter) along with an expression construct coding for high
      level constitutive expression of an Sp1 cDNA led to marked enhancement in
      expression of the LDL receptor reporter gene in quiescent cells. Increased Sp1
      binding due to PDGF could be due to enhanced production of Sp1; alternatively,
      posttranslational activation of binding could be involved. Western blot analysis
      showed no difference in Sp1 abundance in quiescent cells versus PDGF-stimulated
      cells, suggesting a posttranslational mechanism for activation of Sp1 binding by
      growth induction. Our data demonstrate that PDGF stimulation of quiescent cells
      leads to enhanced Sp1 binding to the LDL receptor gene. This enhanced binding
      could participate in PDGF induction of LDL receptor gene transcription.

PMID- 7627720
TI  - Abnormal liver function in patients undergoing autologous bone marrow
      transplantation for hematological malignancies.
AB  - Autologous bone marrow transplantation (AuBMT) is an accepted treatment modality
      for patients with high-risk or relapsed hematological malignancies.
      Hepatotoxicity, in particular veno-occlusive disease (VOD), is a significant
      complication of this therapy. The purpose of this study was to determine the
      clinical relevance of abnormal liver function in the patients who received high
      dose cytotoxic therapy and AuBMT for hematological malignancies at Memorial Sloan
      Kettering Cancer Center. Medical records of 180 consecutive patients between 1984
      and 1991 treated with cytotoxic chemotherapy and AuBMT for acute myelogenous
      leukemia, non-Hodgkin's lymphoma, and Hodgkin's disease were reviewed. Forty-six
      patients (26%) developed jaundice with bilirubin > 4 mg/dl. These patients had a
      43% toxic death rate compared to an 11% toxic death rate in patients with lower
      bilirubins (p < 0.001). The main etiology of hyperbilirubinemia was VOD of the
      liver noted in 22 of the 180 patients (12%). Other etiologies of jaundice
      included hepatitis, sepsis with multiorgan dysfunction, cholecystitis, and
      recurrent disease. Hyperbilirubinemia of various etiologies is a significant
      complication of AuBMT. Several new strategies are under investigation to decrease
      the toxicity of intensive therapy.

PMID- 7627721
TI  - Pilot study of a high-dose carboplatin-based salvage strategy for relapsing or
      refractory germ cell cancer.
AB  - Eleven patients with germ cell cancer relapsing from a complete remission and 7
      patients with refractory germ cell cancer and/or an unresectable partial
      remission received salvage chemotherapy with one to two courses of carboplatin
      (800 mg/m2) and etoposide (500 mg/m2 on days 1, 3, and 5), followed by either one
      or two courses of carboplatin (1600 mg/m2), cyclophosphamide (6 g/m2), and
      thiotepa (480 mg/m2) divided over 4 days with autologous bone marrow
      transplantation and/or peripheral stem cell support. Eight of 11 relapsing
      patients (73%) were salvaged (with a follow-up of 21+ to 56+ months), but only 1
      of the 7 refractory patients survived (34+ months). The high-dose carboplatin
      based salvage regimen is feasible and deserves further evaluation in patients
      relapsing from a complete remission. Even more intensive treatment strategies may
      be required to salvage patients who are refractory to standard doses of
      platinating agents.

PMID- 7627723
TI  - Reduction of toxicity of a vinca alkaloid by an anti-vinca alkaloid antibody.
AB  - Inadvertent oncolytic overdoses occur rarely, but can have serious consequences.
      We have investigated the possibility of using an antibody, 27.8.1A, reactive with
      vinca alkaloids, as a means of reducing the toxicity associated with overdose
      situations. In vitro cytotoxicity of a vinca derivative, 4-desacetyl- vinblastine
      3-carbox-hydrazide (DAVLBHYD), with and without the addition of 27.8.1A, was
      determined. Using CCRF-CEM, a human acute lymphoblastic leukemia cell line, as a
      target in this assay, we observed a greater than 90% increase in cell viability
      using 100 micrograms/ml 27.8.1A with a 0.1 microgram/ml concentration of
      DAVLBHYD. 27.8.1A had no effect on cell viability when doxorubicin was used as a
      control drug in this assay. Similarly, the addition of an irrelevant antibody.
      EGFrL11, had no effect on the toxicity of DAVLBHYD. In an in vivo survival
      experiment, nude mice were injected with a toxic dose of DAVLBHYD and
      subsequently given four doses of 27.8.1A. All anti vinca antibody-treated mice
      survived, in contrast to the untreated group or irrelevant antibody-treated group
      in which only 25% and 10% of the mice survived, respectively.

PMID- 7627722
TI  - Possible predictive markers of immunotherapy in esophageal cancer: retrospective
      analysis of a randomized study. The Cooperative Study Group for Esophageal Cancer
      in Japan.
AB  - The aim of this report is to evaluate retrospectively the data from a prospective
      randomized study of 158 esophageal cancer patients who actually completed therapy
      with protein-bound polysaccharide P (PSK) and the 5-year survivals with and
      without raised alpha 1-antichymotrypsin and sialic acid levels to determine the
      value of these parameters in predicting effectiveness of immunotherapy. There was
      a significant difference in survival between the patients with and without PSK
      therapy. The survival of the radiochemotherapy plus PSK group treated for > 3
      months was significantly better than that of the radiochemotherapy group. Among
      the patients with abnormal levels of alpha 1-antichymotrypsin and sialic acid,
      those who received PSK may have a significantly better survival than those
      without PSK. These results indicate that the preoperative serum levels of alpha 1
      antichymotrypsin and sialic acid may possibly predict the effectiveness of
      immunotherapy using PSK.

PMID- 7627724
TI  - Sacral resection of posterior pelvic malignancy.

PMID- 7627726
TI  - Brachytherapy: criteria for case selection.
AB  - Brachytherapy has an established role in the management of a number of
      malignancies. Contributing to successful application of brachytherapy techniques
      are proper planning, technical sophistication, and meticulous execution. Equally
      important, presumably, is proper case selection although conditions favoring
      brachytherapy utilization are not well described. To facilitate discussion of
      this topic, a semiquantitative system of brachytherapy case selection is
      proposed. Variables considered include the natural history of the malignancy,
      risks involved in the procedure, accessibility of implant site, and results
      obtainable with other treatment modalities. Brachytherapy Case Selection Scores
      (0-8) were generated for a number of malignancies. Higher scores were found for
      sites in which the use of brachytherapy is generally accepted and practiced,
      implying that the clinical factors considered in this system are clinically
      relevant, and that such a system could be useful when considering the use of
      brachytherapy in individual cases. Additional critical analysis regarding
      brachytherapy case selection is desirable.

PMID- 7627725
TI  - Taxanes: a new class of antitumor agents.
AB  - Taxanes belong to a new group of antineoplastic agents with a novel mechanism of
      action for a cytotoxic drug. They promote microtubule assembly and stabilize the
      microtubules. Paclitaxel, the first agent in this group to become available, was
      isolated from the Pacific yew, Taxus brevifolia, in 1971. In preclinical and
      clinical studies, paclitaxel and its semisynthetic analog docetaxel exhibit
      significant antitumor activity. This review deals with the physicochemical
      properties, pharmacology, and results of preclinical and clinical trials of the
      taxanes.

PMID- 7627727
TI  - Possible role of oxidative damage in metal-induced carcinogenesis.
AB  - This review presents and evaluates evidence relevant to the mechanisms of metal
      carcinogenicity with special emphasis on the emerging hypothesis of the oxidative
      nature of metals' effect on DNA. The carcinogenic transition metals are capable
      of in vivo binding with the cell nucleus and causing promutagenic damage that
      includes DNA base modifications, inter- and intramolecular crosslinking of DNA
      and proteins, DNA strand breaks, rearrangements, and depurination. The chemistry
      of that damage and the resulting mutations observed in vitro and in metal-induced
      tumors are both characteristic for oxidative attack on DNA. The underlying
      mechanism involves various kinds of active oxygen and other radical species
      arising from metal-catalyzed redox reactions of O2, H2O2, lipid peroxides, and
      others, with certain amino acids, peptides, and proteins. Other metal-mediated
      pathogenic effects, such as enhancement of lipid peroxidation, stimulation of
      inflammation, inhibition of cellular antioxidant defenses, and inhibition of DNA
      repair, may also contribute to that mechanism. Thus far, published data revealing
      the oxidative character of metal-induced promutagenic DNA alterations are
      particularly strong for two of the most powerful human metal carcinogens,
      chromium and nickel. However, without excluding contribution of other effects,
      the promotion of oxidative damage tends to take the leading role in explaining
      mechanisms of carcinogenicity and acute toxicity of certain other metals as well.

PMID- 7627728
TI  - Wilms' tumor: a paradigm for insights into development and cancer.

PMID- 7627729
TI  - Will CLIA be repealed?

PMID- 7627730
TI  - Neutropenic fever of undetermined origin (N-FUO): why not use the naproxen test?

PMID- 7627731
TI  - Dispensing fees threatened by Medicaid cuts.

PMID- 7627732
TI  - Metformin approved for U.S. market.

PMID- 7627733
TI  - FDA approval of lamotrigine expands epilepsy treatment options.

PMID- 7627734
TI  - Vinorelbine approved for advanced non-small-cell lung cancer.

PMID- 7627735
TI  - Under fire, Joint Commission launches plan for change.

PMID- 7627736
TI  - Avoiding injury from repetitive movement.

PMID- 7627737
TI  - Compensation for cognitive services.

PMID- 7627739
TI  - Incompatibility of fluorouracil with leucovorin calcium or levoleucovorin
      calcium.
AB  - The physical compatibility of fluorouracil mixed with leucovorin calcium or
      levoleucovorin calcium, undiluted and modestly diluted with 5% dextrose
      injection, was evaluated. Fluorouracil 50 mg/mL was combined in duplicate with
      leucovorin or levoleucovorin 20 mg/mL (as the calcium salt) in 250-mL polyvinyl
      chloride (PVC) portable-pump reservoirs in six volume ratios, either undiluted or
      diluted with 5% dextrose injection (to a final volume 25% greater than the drug
      volume). Duplicate reservoirs of each combination were stored for seven days at
      4, 23, or 32 degrees C. Samples were evaluated visually with a high-intensity
      monodirectional light beam to observe development of particulates. Turbidimetry
      and light-obscuration particle counting and sizing also were used to evaluate
      compatibility. Small amounts of tiny crystalline particles developed in most of
      the combinations, usually by four days. In some cases, the particles could be
      seen in normal diffuse room light. Particle content was greater with higher
      leucovorin concentrations and over longer storage periods. Storage temperature
      did not play a consistent role in particle development. Fluorouracil and
      leucovorin calcium or levoleucovorin calcium were not compatible when stored in
      PVC reservoirs at 4, 23, or 32 degrees C.

PMID- 7627740
TI  - Stability of esmolol hydrochloride in 5% dextrose injection.

PMID- 7627738
TI  - Management of alcohol withdrawal.
AB  - The diagnosis, evaluation and assessment, supportive care, and pharmacologic
      treatment of acute alcohol withdrawal are reviewed. Patients in alcohol
      withdrawal have decreased or stopped their heavy, prolonged ingestion of alcohol
      and have subsequently begun to have at least two of the following symptoms:
      autonomic hyperactivity, tremor, nausea or vomiting, hallucinations, psychomotor
      agitation, anxiety, and grand mal seizures. Evaluation of the patient at risk for
      alcohol withdrawal should include a complete history and physical examination;
      laboratory tests are often indicated. The patient's progress should be assessed
      before, during, and after therapy, preferably with a validated instrument. After
      the initial evaluation and assessment but before the administration of dextrose
      containing solutions, a 100-mg dose of thiamine hydrochloride should be given by
      i.m. or i.v. injection. Routine supplementation with calcium, magnesium, and
      phosphate is questionable. The need for fluid and electrolyte administration
      varies depending on losses. Most patients in alcohol withdrawal can be managed
      with supportive care alone, but for more severe or complicated withdrawal,
      pharmacologic therapy may be necessary. Benzodiazepines, especially diazepam and
      chlordiazepoxide, are the drugs of choice. Barbiturates, beta-blockers, and
      antipsychotics are generally not recommended as first-line therapy. Several drugs
      in other classes, including carbamazepine and clonidine, have been shown to be
      about as effective as benzodiazepines in a few studies, but the studies were
      small, the patients were usually in mild withdrawal, and validated instruments
      for assessing withdrawal were often not used. Some agents, such as beta-blockers,
      may play a role as adjuncts to, not replacements for, benzodiazepine therapy. For
      patients in alcohol withdrawal who do not respond to supportive care,
      benzodiazepines are the treatment of choice.

PMID- 7627741
TI  - Dangers of compromising drug distribution.

PMID- 7627742
TI  - Criteria for use of continuous midazolam infusion in adult inpatients.

PMID- 7627743
TI  - Are pharmacies in teaching hospitals really less efficient?

PMID- 7627744
TI  - Were the bubbles evolved or entrained?

PMID- 7627745
TI  - Clarification of case-cost method.

PMID- 7627746
TI  - The moral status of the fetus.

PMID- 7627747
TI  - PREP: what will it mean for you?

PMID- 7627748
TI  - Toxoplasmosis: survey of policy and practice in UK antenatal clinics.

PMID- 7627749
TI  - Special care liaison midwife.

PMID- 7627751
TI  - RCM Standing Practice Group. Paper 4: The use of intravenous infusions by
      midwives.

PMID- 7627750
TI  - The care of gestational diabetics and women with diabetes during their
      childbearing years.

PMID- 7627752
TI  - Extensibility of the normo-hydrated human cornea.
AB  - The extensibility of 10 human corneas was evaluated in vitro by measuring central
      epithelial side and endothelial side tangential strain induced by intraocular
      pressure loads ranging from 2 to 100 mmHg. Corneal normo-hydration was attempted
      by immersing and perfusing the eyes with 8% Dextran 500 in isotonic saline. The
      relationship between corneal strain and intraocular pressure was found to be non
      linear, showing a typical stress-stiffening behaviour. Strain changes were
      approximately 10% higher on the endothelial side compared with the epithelial
      side. This difference could be fully explained by pressure induced changes in
      corneal volume. Compared to previous experiments performed on swollen corneas,
      the stiffness of the normo-hydrated human cornea was found to be higher. Young's
      modulus of elasticity for the corneal stroma was estimated to 3, 9, and 20 MPa
      for intraocular pressure intervals of 2-10, 10-25, and 25-100 mmHg, respectively.

PMID- 7627753
TI  - Effect of excimer laser keratectomy on the mechanical performance of the human
      cornea.
AB  - Enucleated human eye globes were set-up for measurements of pressure (2-100 mmHg)
      induced tangential epithelial and endothelial side corneal strain, and for
      measurements of central corneal thickness and central radius of curvature. In one
      experimental group (N = 6), a shallow ablation (15-20 microns deep) removing
      Bowman's layer was performed in the central 7 mm diameter zone of the cornea. The
      fellow eye served as control (N = 6). In another experimental group (N = 6) a 70%
      deep keratectomy was performed in the central 7 mm diameter zone. The pressure
      induced central corneal strain was 5-10% higher in corneas without Bowman's layer
      compared with intact corneas. The epithelial side tangential corneal strain in
      eyes with a 70% deep keratectomy increased to twice as much as that of intact
      corneas, but the endothelial side strain was similar. In all groups of eyes
      Young's modulus of elasticity increased rapidly with the corneal stress level up
      to testing loads of 25 mmHg. At higher loads the degree of stress-stiffening was
      smaller. The differences in average corneal strain between the 3 groups could be
      explained by the induced changes in central corneal thickness, as there were no
      statistically significant differences in stress-normalized Young's modula of
      elasticity between the 3 groups. The central radius of curvature did not change
      significantly with increasing pressure in intact eyes or in eyes without Bowman's
      layer. In deep keratectomized corneas the corneal radius of curvature decreased
      approximately 1% when the intraocular pressure was increased from 2 to 100
      mmHg.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7627754
TI  - Corneal astigmatism. The effect of transverse corneal incisions.
AB  - The results of transverse or combined transverse and radial keratotomy in eyes
      with idiopathic corneal astigmatism (N = 11), astigmatism+myopia (N = 9) or early
      stages of keratoconus (N = 6) are presented. The corneal astigmatism was reduced
      in all our patients, the absolute reduction being significantly correlated to the
      degree of preoperative astigmatism (p = 0.007). In the whole study group the mean
      relative reduction of the corneal astigmatism was 52.7%. In eyes without
      keratoconus the astigmatism recorded at the last follow-up visit was very similar
      to that measured a few days after surgery, while greater changes occurred in the
      keratoconus group.

PMID- 7627756
TI  - The 1994 Fernstrom Prize, Sweden.

PMID- 7627755
TI  - Recurrence and rejection rates following corneal transplantation for herpes
      simplex keratitis.
AB  - Seventy-two penetrating primary keratoplasties for herpes simplex keratitis
      performed from 1970 to 1993 were reviewed. Postoperative follow-up periods ranged
      from 6 months to 16 years with 2 years median. Epithelial herpetic recurrence
      occurred in 25% of the transplants the first year and in 44% during the first 2
      years. Primary allograft rejection was observed in 29% of the grafts the first
      year and in 46% during the first 2 years. Preoperative inflammation was a risk
      factor for preservation of a clear cornea (p < 0.10). The degree of corneal
      vascularization prior to operation did not influence the survival of the grafts.
      The overall one-year survival rate of a clear graft was 84% and the 2-year
      survival rate was 67%. Prophylactic antiviral treatment is discussed.

PMID- 7627757
TI  - A national Cataract Register. I. Description and epidemiology.
AB  - In 1992 a Swedish National Cataract Register was instituted. More than 90% of all
      cataract surgeries are performed at community run eye clinics. All community run
      eye clinics in the country participated and 89% of all cataracts performed are
      included in this register. In total 31,679 eyes were entered. All the pertinent
      preoperative information on these patients can be found in the register. As
      indicated in other studies two-thirds of the surgeries were performed on women
      and one-third of the surgeries was performed on second eyes. The number of
      surgeries equals 4.5 per 1000 inhabitants and this figure has steadily increased
      since 1980.

PMID- 7627758
TI  - Progression of lens opacities in cataract patients after one year.
AB  - We used the Lens Opacities Classification System II to clinically grade the
      lenses of 57 patients with age-related cataracts in at least one eye. Progression
      or regression in each lens region was defined as a one or more step change in the
      Lens Opacities Classification System II grading noted at 1 year and maintained at
      the 1 1/2 to 2 year visit (the validation visit). A validated change in a lens
      region in one eye of a patient was considered a change in that region for that
      patient. Person-specific rates of cataract progression at 1 year were 42% for
      nuclear, 32% for cortical and 10% for posterior subcapsular opacities.
      Corresponding regression rates were 5%, 4%, and 2% for nuclear, cortical and
      posterior subcapsular opacities, respectively. Progression rates were
      significantly greater than the regression rates only for nuclear and cortical
      opacities (p < 0.0005). These findings show the applicability of the clinical
      Lens Opacities Classification System II method in documenting and monitoring lens
      changes over time. The usefulness of person-specific analysis was also shown.

PMID- 7627759
TI  - In vitro measurement of corneal strain, thickness, and curvature using digital
      image processing.
AB  - A video camera, a microscope, and a PC-based digital image processing board were
      assembled for in vitro studies of corneal biomechanics. Central tangential
      corneal strain was determined by placing pairs of tiny mercury droplets on the
      epithelial surface and on the endothelial surface of the cornea. A distance of
      3.2 mm could be determined with a standard deviation of 1.2 micron. Central
      corneal radius of curvature was measured from digital traces of the corneal
      surface contour. The standard deviation on estimating the radius of an 8 mm steel
      sphere was 15 microns. Corneal thickness was measured by digital optical
      pachometry. The standard deviation on measuring a thickness of 1 mm was 4.6
      microns. The corneal extensibility was investigated in a total of 10 enucleated
      human eyes with increased corneal hydration. Tension was applied by varying the
      intraocular pressure from 2 to 100 mmHg with a column of isotonic saline. The
      epithelial side corneal strain and the increase in corneal curvature were
      approximately 1% for a change in intraocular pressure from 2 to 100 mmHg. When a
      high intraocular pressure was kept constant for 2 h the corneal thickness, radius
      of curvature, and the epithelial side strain gradually decreased, whereas the
      endothelial side strain increased. The elastic and visco-elastic behaviour of the
      human cornea was found to be closely related to changes in corneal hydration. We
      found digital image processing useful for in vitro biomechanical studies of the
      cornea.

PMID- 7627760
TI  - Contrast visual acuities in cataract patients. III. Changes of contrast acuity
      profiles in normal and pathological eyes.
AB  - We compared pre- and postoperative visual acuities in 45 cataract patients
      without ocular pathology except lens opacity (group 1) and 20 patients with
      ocular pathologies and lens opacity (group 2) using Variable Contrast Visual
      Acuity Charts. Charts 1 and 4 have 90% contrast; chart 4 has white optotypes on a
      black background (reverse polarity), charts 2 and 3 have 15% and 2.5% contrast,
      respectively. The mean preoperative visual acuities of groups 1 and 2 measured
      with the high-contrast Landolt optotypes ranged from 0.02-0.80 and 0.22-0.40,
      respectively. Visual acuity improvements between the pre- and postoperative
      periods ranged from 1.37-1.61 and 0.52-1.24 octaves in groups 1 and 2,
      respectively, with the different charts. Visual acuity improvement was poorest
      with chart 3. The group 1 mean preoperative visual acuity measured with chart 2
      was 1.11 octaves lower than with chart 1. In group 2, the visual acuity reduction
      was 1.81 octaves. The relation between the visual acuities measured with the high
      contrast intermediate-contrast optotypes are important for predicting
      postoperative visual acuity improvement. An abnormal contrast acuity profile may
      indicate the presence of additional ocular pathologies.

PMID- 7627761
TI  - Retrobulbar anesthesia with and without adrenaline in extracapsular cataract
      surgery. A prospective, randomized, double-blind study.
AB  - Seventy-five patients with senile cataract underwent a planned extracapsular
      cataract extraction. They were randomly divided into two groups, receiving
      retrobulbar anesthesia (4 ml lidocaine 2% and 250 IU hyaluronidase) with or
      without adrenaline. Patients in the adrenaline group had the lowest mean
      intraocular pressure after the retrobulbar injection (p < 0.02) and they required
      a shorter time of digital bulbar massage to reduce tension before surgery (p <
      0.01). They also appeared to have a deeper anterior chamber during the first part
      of surgery, although the difference was not statistically significant. The
      duration of postoperative analgesia was significantly prolonged in patients
      receiving adrenaline. Different mechanisms explaining the effects of adrenaline
      in retrobulbar anesthesia are discussed.

PMID- 7627762
TI  - Video controlled M-mode biometry.
AB  - To increase the accuracy of intraocular lens power calculation, an interface
      between an ultrasonic A-scanning device and a personal computer was created,
      allowing for an on-line interpretation of the ultrasonogram in an M-mode fashion.
      On the same computer display, a video recording of the movements of the
      transducer probe relative to the eye was inserted to obtain simultaneous
      information on the external alignment of the transducer probe. The precision of
      the experimental set-up in the measurement of intraocular distances was compared
      with conventional A-scanning procedures run in automatic mode. The video
      controlled M-mode biometry was found easy to operate and to result in
      reproducible axial length determination: The median value of the standard
      deviation was found to be below 0.04 mm as compared to a value of about 0.10 mm
      with conventional equipment. We concluded that video controlled M-mode biometry
      has great potential in the endeavour to increase the accuracy of intraocular lens
      calculation.

PMID- 7627763
TI  - Ocular hemodynamic changes in patients with high-grade carotid occlusive disease
      and development of chronic ocular ischaemia. I. Doppler and dynamic tonometry
      findings.
AB  - Ophthalmic artery blood flow pattern and the pulsatile ocular blood volume
      changes in patients with hemodynamically significant carotid occlusive disease
      are described. Using transorbital Doppler ultrasonography and dynamic tonometry
      45 patients with high-grade internal carotid artery stenosis or occlusion and 15
      healthy controls were examined. The measurements were performed under baseline
      conditions and 30 min after 1 gi.v. acetazolamide administration. The velocity in
      the ophthalmic artery was significantly lower in patients compared with controls.
      Pulsatile ocular blood volume was also lower in patients than in controls under
      baseline conditions, and a further reduction was found after acetazolamide,
      despite the significant decrease of intraocular pressure. A different reaction
      was observed in eyes with chronic ocular ischaemia.

PMID- 7627764
TI  - Do we operate too many cataracts? The referred cataract patients' own appraisal
      of their need for surgery.
AB  - A questionnaire was sent to 379 patients referred for cataract extraction, asking
      them to assess their visual disability and their need for surgery. Two hundred
      and seventy-nine patients (73.6%) answered the questionnaire, this group being
      representative for the 379 patients regarding all relevant variables. The
      patient's answers were analyzed in relation to data extracted from their referral
      notes (visual acuity, monocular pseudophakia, age, sex, place of residence,
      referring ophthalmologist). The overall level of self-reported visual problems
      and need for cataract surgery were significantly correlated to a reduced best-eye
      visual acuity, although the correlation factor was low. A similar correlation
      between the subjective need for surgery and a worst-eye visual acuity < or = 6/24
      was also found. Forty-seven patients (16.9%) answered that cataract surgery was
      not needed for the time being, and this attitude was not significantly correlated
      to the visual acuity, provided the acuity was > or = 6/24 in the best eye and >
      or = 6/36 in the worst eye. One hundred and twenty patients (43.0%) felt that
      their visual disability was so severe that they had to be operated within 1 month
      and 67 patients (24.0%) within 3 months, while 45 patients (16.1%) felt that
      surgery could be postponed for at least 6 months. Age, sex, place of residence
      and the presence of monocular pseudophakia were not found to significantly
      influence the level of self-reported visual problems. Only 18.3% preferred to be
      treated as out-patients.

PMID- 7627765
TI  - Multiple myeloma presenting with bilateral exudative macular detachments.
AB  - Bilateral exudative macular detachments were present on a 64-year-old diabetic
      Caucasian male who presented with bilateral blurring of vision. Besides the
      exudative macular detachments there was no diabetic retinopathy or congestive
      retinopathy, and a previous fluorescein angiogram revealed no focal leakage.
      Laboratory investigation, bone marrow biopsy, and a bone survey revealed the
      diagnosis of multiple myeloma.

PMID- 7627766
TI  - Presumed ophthalmic herpes zoster after contralateral cataract extraction.
AB  - Herpes zoster ophthalmicus (HZO) may occur spontaneously, but can be precipitated
      by stress, trauma, debility or systemic illness. A case is here reported of
      Herpes zoster involving the contralateral eye, associated with a midline skin
      rash, following cataract extraction under local anaesthesia.

PMID- 7627767
TI  - The ultrasound biomicroscope (UBM)

PMID- 7627768
TI  - Inadvertent instillation of Minims eye drops in an ophthalmic casualty
      department.

PMID- 7627769
TI  - Body mass index and coronary artery disease in African-Americans.
AB  - There are limited data available concerning the influence of obesity, a major
      cardiovascular disease risk factor, in relationship to coronary artery disease
      (CAD). This is of considerable importance to African-Americans since African
      Americans have one of the world's highest CAD mortality rates coupled with the
      fact that obesity is extremely prevalent in this population. The present study
      assessed the relationship between body mass index and CAD in African-Americans
      undergoing coronary angiography. Eight hundred sixty-six available cardiac
      catheterization reports between the years 1983 through 1990 were retrospectively
      reviewed at Howard University Hospital in Washington, D.C. CAD was prevalent in
      59.6% and 41.2%, males and females, respectively. Among the males overweight and
      obesity were found in 22.4% and 20.9%, respectively, compared to 39.6% and 30.6%
      for females. An upside-down U-shaped relationship between BMI and CAD was found.
      The interpretation of this finding is that being overweight is associated with
      increased risk of CAD compared to the lean and obese.

PMID- 7627770
TI  - Fatness and physical fitness of girls 7 to 17 years.
AB  - A two-fold approach was used to investigate the association between fatness and
      fitness of girls 7 to 17 years of age: first, age-specific correlations between
      fatness and measures of health-related and motor fitness, and second, comparisons
      of fitness levels of girls classified as fat and lean. A representative sample of
      6700 between 7 to 17 years was surveyed. Adiposity (fatness) was estimated as the
      sum of five skinfolds (biceps, triceps, subscapular, suprailiac, medial calf).
      Physical fitness included health-related items (step test, PWC170, the sit and
      reach, sit-ups and leg lifts, flexed arm hang) and motor performance items
      (standing long jump, vertical jump, arm pull strength, flamingo stand, shuttle
      run, plate tapping). Age-specific partial correlations between fatness and each
      fitness item, controlling for stature and weight, were calculated. In addition,
      in each age group the fattest 5% (presumably the obese) and the leanest 5% were
      compared on each fitness test. After controlling for stature and weight,
      subcutaneous fatness accounts for variable percentages of the variance in each
      fitness item. Estimates for health-related fitness items are: cardiorespiratory
      endurance-step test (3% to 5%) and PWC170 (0% to 16%), flexibility-sit and reach
      (3% to 8%), functional strength-flexed arm hand (6% to 17%) and abdominal
      strength-sit-ups/leg lifts (1% to 8%). Corresponding estimates for motor fitness
      items are more variable: speed of limb movement-plate tapping (0% to 3%), balance
      flamingo stand (0% to 5%), speed and agility-shuttle run (2% to 12%), static
      strength-arm pull (4% to 12%), explosive strength-standing long jump/vertical
      jump (11% to 18%). At the extremes, the fattest girls have generally poorer
      levels of health-related and motor fitness.

PMID- 7627772
TI  - Maintenance of weight loss: a needs assessment.
AB  - This study identified facilitators and obstacles to maintenance of weight loss
      following a very-low-calorie-diet and behavior modification program. A survey was
      mailed to a random sample of 178 program completers and received a 61% response
      rate; the most frequent follow-up period was more than 2 years. Twenty-nine
      percent reported weighing the same (within 10 lbs) or less than the end of their
      participation in the treatment program (maintainers), while 71% reported their
      present weight was a mean of 65% higher than their initial weight loss
      (regainers). Maintainers were significantly more likely to report engaging in
      regular aerobic exercise, attending a maintenance support group, and confidence
      in their ability to manage their weight in the future, while regainers were more
      likely to report stress and motivation as frequent weight management obstacles.
      Respondents consistently identified the need for low/no cost ongoing support.
      Maintainers and relapsers reported similar challenges in managing their weight,
      yet with different results, suggesting the need to identify subgroups for which
      different post-treatment support options could be applied.

PMID- 7627771
TI  - Blockade of the glucocorticoid receptor with RU 486: effects in vitro and in vivo
      on human adipose tissue lipoprotein lipase activity.
AB  - Cortisol is known to induce lipoprotein lipase (LPL) activity in human adipose
      tissue in vitro and in vivo such as in Cushing's syndrome. The significance of
      the glucocorticoid receptor (GR) for this induction was evaluated in the present
      study. The synthetic steroid molecule RU 486, a potent glucocorticoid antagonist,
      was used as a tool to block the GR, in vitro and in vivo. In addition to LPL
      activity, glucose tolerance, blood pressure and plasma lipids, all variables
      influenced by cortisol, were studied in order to evaluate the peripheral
      antiglucocorticoid activity of RU 486 in vivo, in man. Addition of both cortisol
      and RU 486 to incubations of human adipose tissue pieces significantly inhibited
      the increase in LPL activity that could be induced by cortisol alone (p < 0.01).
      In a ten-fold molarity excess RU 486 totally abolished cortisol action (p <
      0.01). With cortisol and RU 486 in equimolar concentrations the RU 486 blockade
      was probably incomplete and LPL activity induced (p < 0.05). The results imply
      that the stimulating effect of cortisol on LPL activity in human adipose tissue
      is mediated via the GR. Administration of 400 mg RU 486 at 2200 hours on two
      consecutive days to healthy men caused a significant rise in serum cortisol
      levels measured at 0800 hours (p < 0.05). The mean LPL activity in the
      subcutaneous abdominal adipose tissue remained unchanged. The mean level of serum
      triglycerides decreased significantly (p < 0.01) and there was a negative
      correlation between change in LPL activity and change in triglyceride levels (r =
      -0.73, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7627773
TI  - DNA polymorphisms in the alpha 2- and beta 2-adrenoceptor genes and regional fat
      distribution in humans: association and linkage studies.
AB  - The aim of this study was to investigate the relationships between DNA
      restriction fragment length polymorphisms (RFLP) in the alpha 2- and beta 2
      adrenoceptor genes and body fat distribution in humans. Skinfold thickness
      measurements and genetic analyses (Southern blot) were performed on 280
      individuals (142 parents and 138 offsprings) from the Quebec Family Study. Using
      the association study design in unrelated adults, women but not men carrying the
      6.3-kb allele of an alpha 2A-adrenoceptor/DraI RFLP had a significantly higher
      trunk to extremity skinfold ratio (= sum of subscapular+suprailiac+abdominal
      skinfolds/sum of biceps+triceps+medial calf skinfolds) compared to women without
      the allele (1.44 +/- 0.52 vs. 1.12 +/- 0.33; p < 0.005 after adjustment for age,
      p < 0.002 after adjustment for age and body mass index or for age and
      subcutaneous fat). Using the sib-pair linkage procedure, a significant inverse
      relationship was found between the proportion of alleles identical by descent
      shared by sibs at the alpha 2A RFLP marker locus and the squared differences of
      the trunk to extremity skinfold ratio (p = 0.02 after adjustment for age or for
      age and body mass index or for age and subcutaneous fat). For a beta 2
      adrenoceptor/BanI RFLP, no significant association or linkage was found between
      fat distribution indicators and the marker. These results suggest that alpha 2A
      adrenoceptor gene variability detected with DraI is associated with a relative
      subcutaneous fat pattern favoring accumulation of truncal-abdominal fat in women,
      and that the alpha 2A-adrenoceptor gene, or a locus in close proximity, may be
      linked to body fat distribution in humans independently of the overall level of
      fatness.

PMID- 7627774
TI  - Physical activity as a predictor of weight maintenance in previously obese
      subjects.
AB  - We examined the association between exercise and weight loss maintenance in a
      group of 45 previously obese subjects 2 years post very-low-calorie diet (VLCD)
      to suggest exercise goals for this population. At baseline, subjects weighed a
      mean 100 kg and had a mean total cholesterol (TC) of 5.8 mmol/L. With VLCD they
      lost an average 28 kg and decreased their TC by 1.6 mmol/L. Two years post-VLCD
      their weight and lipids were measured and they completed a physical activity
      survey (Paffenbarger). Subjects were grouped into tertiles by reported exercise
      levels: low active (< 850 kcals per week), moderate active (850-1575 kcals per
      week) and high active (> 1575 kcals per week). Walking accounted for the greatest
      calorie expenditure (65%). Analysis of variance showed that baseline
      characteristics and weight and blood lipid changes during the VLCD did not differ
      (P > 0.05) among groups. At follow-up, high active patients maintained
      significantly greater weight loss, had a lower percent regain and a significantly
      greater decrease in total cholesterol (P < 0.05) than less active patients.
      Multiple regression analysis indicated that total exercise calories independently
      predicted overall weight loss and percent regain (r = 0.66 and r = 0.62,
      respectively). Exercise calories also predicted total cholesterol change (r = 
      0.37). The high active group walked more miles (16.2 per week) than the low and
      moderate active groups (4.8 and 9.1 per week, respectively) and exercised more
      days per week (5.3 vs. 1.9 and 3.7).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7627775
TI  - Monoclonal antibody-mediated cytotoxicity of adipocytes.
AB  - Monoclonal antibodies (MAbs) raised against porcine adipocyte plasma membranes
      were used to demonstrate complement-mediated cytotoxicity of adipocytes and
      preadipocytes in primary stromal-vascular (SV) cultures. Five of the six MAbs
      tested significantly reduced the number of fat cell clusters in cultures
      maintained in medium supplemented with pig serum and dexamethasone (PS/DEX) but
      not in cultures supplemented with insulin, transferrin, and selenium (ITS).
      Neither MAb nor complement alone affected fat cell cluster number. Treatment of
      both ITS and PS/DEX cultures with pools of 2 or more MAbs, in combination with
      complement, eliminated fat cell clusters in all instances. Treatment of cultures
      prior to appearance of cells containing lipid demonstrated that preadipocytes, or
      adipose lineage cells, could also be eliminated by MAb/complement treatment.
      Finally, injection of young rats with a pool of three of the MAbs produced a 30%
      reduction in inguinal fat pad weight without affecting other tissues.
      Adipocyte/preadipocyte-depleted cultures can now be used as a model system to
      examine progression of cells through the adipose cell lineage at a time not
      previously possible with primary cells.

PMID- 7627776
TI  - Searching for the association of obesity with coronary artery disease.

PMID- 7627777
TI  - Obesity in children: recent advances in energy metabolism and body composition.
AB  - In this paper we review recent advances in energy metabolism and body composition
      studies in prepubescent children and the relationship to childhood obesity. Our
      review on energy expenditure focusses on studies of total energy expenditure
      using doubly labeled water, the role of energy expenditure in the development of
      obesity, and the determinants of resting energy expenditure in children. The
      relatively few studies that have examined the regulation of energy and
      macronutrient intake in children are also reviewed. In terms of body composition,
      we focus on recent methodological studies that have developed existing techniques
      for application to the pediatric population, including dual energy X-ray
      absorptiometry and bioelectrical resistance. Lastly, we review existing
      information relating to measurement and alteration of body fat distribution in
      children.

PMID- 7627778
TI  - Measurement of body composition: an improving art.

PMID- 7627781
TI  - Pathophysiology of ischemic heart disease: an overview.
AB  - Ischemia refers to inadequate supply of oxygen and metabolic substrate to an
      organ. The term myocardial ischemia covers a heterogeneous group of clinical
      syndromes, globally called ischemic heart disease, which includes chronic stable
      angina at one end of the spectrum and acute myocardial infarction at the other
      end. Between these two extremes, there is a broad myriad of intermediate
      syndromes, all having in common a mismatch between oxygen demand and supply.
      Ischemic heart disease is the leading cause of all morbidity and mortality in the
      United States. It is reasonable to assume that proper intervention and follow-up
      care based on knowledge of pathophysiology is imperative to the professional
      nursing care of patients with this disease. In this article, the author presents
      a brief survey of the current state of the discussion from a pathophysiologic
      viewpoint that highlights the dynamic nature of the disease and its related
      clinical implications.

PMID- 7627780
TI  - Stability of basal metabolic rate over selected days of the menstrual cycle.

PMID- 7627779
TI  - The specific gravity of healthy men. Body weight divided by volume as an index of
      obesity. 1942.

PMID- 7627782
TI  - Diagnosis and treatment of acute myocardial infarction.
AB  - Rapid diagnosis and treatment of myocardial infarction are essential for
      maximizing patient survival. Recent advances in early detection of creatine
      kinase myocardial band isoforms and other chemical markers, as well as increased
      use of echocardiography, magnetic resonance imaging, and nuclear imaging, have
      enhanced the diagnostic capabilities for providers caring for a patient suspected
      of myocardial infarction. In management of myocardial infarction, the focus
      continues to be primarily on using thrombolytics, percutaneous transluminal
      coronary angioplasty, and coronary bypass surgery. In addition, an array of
      pharmacologic agents aimed at reducing cardiac muscle damage, alleviating
      reperfusion injuries, and preventing thrombus formation are undergoing clinical
      trials. These agents may hold promise for the future treatment of myocardial
      infarction.

PMID- 7627783
TI  - Primary angioplasty in the acute myocardial infarction setting.
AB  - Management of patients experiencing an acute myocardial infarction has evolved
      dramatically during the past 2 decades. The role and timing of percutaneous
      transluminal coronary angioplasty in patients experiencing a myocardial
      infarction has remained controversial and under investigation. In recent studies,
      it was revealed that direct use of percutaneous transluminal coronary angioplasty
      in the presence of an acute myocardial infarction appears to be a safe,
      effective, and economical method of reperfusion.

PMID- 7627784
TI  - Myocardial protection during cardiac surgery.
AB  - Increased understanding of the effects of ischemia on the myocardium has led to
      advances in the field of myocardial protection during cardiac surgery. These
      advances, combined with improved surgical techniques, have contributed to the
      success of cardiac surgery and the ability to revascularize high-risk
      populations. The most common technique used to protect the myocardium is
      cardioplegia administration. Although it is the surgeon's responsibility to
      decide on solution composition, temperature, and direction of delivery, it is the
      bedside nurse who monitors the patient after surgery. Armed with knowledge about
      the essential concepts of myocardial protection, the critical care nurse will be
      prepared to care adequately for the patient after cardiac surgery.

PMID- 7627785
TI  - Pharmacotherapy of ischemic heart disease.
AB  - The pharmacotherapy of ischemic heart disease has evolved at a rapid pace during
      the past several decades. Drug therapy is prescribed for ischemic heart disease
      to either increase myocardial oxygen supply, decrease myocardial oxygen demand,
      or both. Although the types and number of drugs to treat ischemic heart disease
      are increasing and will continue to do so, there are still several major
      categories of pharmacologic agents that are essential in managing ischemic heart
      disease. The major drug categories covered are antiplatelet agents,
      anticoagulants, nitrates, beta-adrenergic receptor antagonists (beta-blockers),
      calcium channel antagonists, angiotensin-converting enzyme inhibitors, and
      thrombolytic agents. Current information and recommendations are presented for
      safe and effective use of these agents.

PMID- 7627786
TI  - Implementing new dietary guidelines of the National Cholesterol Education
      Program.
AB  - The aggregate cost of coronary heart disease in the United States is between $50
      billion and $100 billion per year. The most cost-effective method of reducing
      this is by health education. In 1993, the National Cholesterol Education Program
      released its second report containing the updated recommendations for the
      evaluation and treatment of people with high levels of total cholesterol and low
      density lipoprotein cholesterol. The new guidelines emphasize the importance of
      maximizing the benefits of nondrug therapies (e.g., diet, weight loss, and
      exercise) before adding pharmacologic therapy. The nutrition counselor teaches
      clients the National Cholesterol Education Program dietary guidelines through
      assessing, motivating, implementing, and monitoring adherence and therapeutic
      response. It is important to stress which foods to use or decrease and to give
      specific examples that apply in everyday life. The addition of drug therapy
      should be considered carefully and reserved for high-risk patients, only after
      sufficient application of dietary therapy, weight control, and physical exercise
      have been attempted.

PMID- 7627787
TI  - Cardiac rehabilitation in the time of health-care reform.
AB  - Cardiac rehabilitation has evolved into a medically efficacious, cost-effective
      intervention for patients with ischemic heart disease. Most aspects of this
      therapy are well developed, and guidelines for programs exist. As the health-care
      delivery system undergoes scrutiny and evolution, it would be prudent for the
      practitioners of cardiac rehabilitation to evaluate the methods they use to
      deliver their services. Program administrators should reconsider traditional
      approaches that are largely based on reimbursement criteria. Goal-directed,
      patient-centered service delivery will allow individualization of care. A model
      for such an approach to cardiac rehabilitation is presented.

PMID- 7627788
TI  - Creative solutions: home dobutamine infusions.
AB  - The increase in the number of congestive heart failure patient hospitalizations
      each year poses a challenge to the nurses caring for this population. Numerous
      alternatives to hospital care must be explored. The use of dobutamine infusions
      in the home is a particular challenge. In this article, the pathophysiology and
      signs and symptoms of congestive heart failure are summarized. In addition, the
      pharmacology, clinical effects, and side effects of dobutamine are addressed.
      Recommendations are suggested for selection of patients for home therapy, dosage,
      administration, and monitoring parameters for follow-up. Finally, therapeutic
      endpoints are discussed, as well as financial benefits of home dobutamine
      infusion.

PMID- 7627789
TI  - Ventricular dysrhythmias in ischemic heart disease.
AB  - Ischemic heart disease remains a leading killer in industrialized nations. A
      significant cause of the morbidity and mortality in patients with ischemic heart
      disease is ventricular dysrhythmic events. There is a continued search for safe
      and effective treatment for patients with ventricular dysrhythmias. In this
      article, the author discusses current understanding of the mechanisms for
      dysrhythmias in the setting of acute ischemia and in the chronically infarcted
      ventricle. Therapy for patients with ventricular tachycardia and ventricular
      fibrillation is reviewed. Nurses caring for cardiac patients are continually
      involved in rhythm monitoring and dysrhythmia interpretation. The nurse is often
      the first responder present when a fatal dysrhythmia occurs. In addition, nurses
      can be involved at all levels of care, from prevention of heart disease to
      assisting the patient cope with a sudden cardiac death episode.

PMID- 7627790
TI  - Postpericardiotomy syndrome: a complication of cardiac surgery.
AB  - Postpericardiotomy syndrome is a frequent complication of cardiac surgery and is
      characterized by fever, chest pain, and a pericardial friction rub. Based on
      current evidence, there may be an immunologic basis to this syndrome. Treatment
      is aimed at reducing inflammation and promoting comfort. Although this syndrome
      is usually benign and self-limiting, it can recur and has been complicated by
      cardiac tamponade and early bypass graft closure.

PMID- 7627791
TI  - The heart of aging: special challenges of cardiac ischemic disease and failure in
      the elderly.
AB  - The elderly are the fastest-growing segment of society, and heart disease is the
      single-most common cause of death in this population. In this article, age
      related structural and functional changes that occur in the heart are discussed,
      including changes in the heart muscle, valves, conduction system and major
      arteries. Coronary artery disease affects half of those older than 65, resulting
      in acute myocardial infarction, angina pectoris, dysrhythmias, congestive heart
      failure and sudden death. Each of these is discussed, including altered
      presentation in the elderly and implications for practice derived from national
      and international studies.

PMID- 7627792
TI  - Reducing length of stay in patients undergoing open heart surgery: the University
      of Pittsburgh experience.
AB  - The clinical pathway, one component of the case management model, was implemented
      at one university medical center in the coronary artery bypass surgical group. In
      this article, the authors describe the development, use, and evaluation of the
      clinical pathway. The role of the advanced nurse practitioner as the case manager
      is discussed. The initial data base created by the case manager includes patient
      demographics, daily progress, length of stay, charges, discharge disposition, and
      readmissions within 15 days. Data collected on all patients undergoing coronary
      artery bypass graft surgery from July 94 to October 94 are reported and compared
      with the benchmark set with the development of the clinical pathway. Strategies
      developed for future improvement in the clinical pathway process and data
      management are identified.

PMID- 7627793
TI  - Reporting practice.

PMID- 7627794
TI  - Treatment of a malignant leg ulcer.

PMID- 7627795
TI  - A comparison of pressure-relieving surfaces using two measures of pressure.

PMID- 7627796
TI  - Photography in wound assessment.

PMID- 7627797
TI  - The aetiology and healing rates of chronic leg ulcers.
AB  - Data from published studies of leg ulcer aetiology concentrate on venous and
      arterial disease as the main aetiological factors. The records of 490 patients
      attending leg ulcer clinics over a two-year period in 1992 and 1993 were
      reviewed. Although 58% of the ulcers studied resulted from venous disease, the
      remainder were caused by a wide range of factors. Our venous ulcer healing rate
      of 53% at six months was not as impressive as other published data, although this
      can be accounted for. By comparing the management and outcome for ulcers of
      various aetiologies, it was shown that they require different methods of
      treatment, often including referral to another specialty. Ulcers also exhibit
      differential healing rates depending on the underlying aetiology. Some ulcer
      aetiologies, particularly vasculitis, present particular problems and have very
      poor healing rates.

PMID- 7627798
TI  - Doppler ultrasound recording of ankle brachial pressure index in the community.

PMID- 7627799
TI  - Hospital mattresses and pressure sore prevention.

PMID- 7627800
TI  - Assessment of fungating malignant wounds.

PMID- 7627801
TI  - Is the osteopetrotic (op/op mutant) mouse completely deficient in expression of
      macrophage colony-stimulating factor?
AB  - The op/op mouse has a mutation in the macrophage colony-stimulating (CSF-1) gene.
      The phenotype of gross deficiency in the macrophage and osteoclast lineages
      corrects significantly with age, suggesting that other factors can substitute for
      CSF-1. This review examines the evidence that the op/op mouse is completely CSF-1
      deficient and considers the possibility that alternative splicing within the CSF
      1 gene might bypass the mutation, yielding an incompletely penetrant phenotype.

PMID- 7627802
TI  - Antiproliferative and recovery effects during treatment of breast and ovarian
      carcinoma cell cultures with interferon-gamma.
AB  - We studied the antiproliferative effects of human interferon-gamma (IFN-gamma) on
      cell lines derived from human carcinomas (three breast, two ovarian, and one
      renal) and recovery from these effects when IFN-gamma was removed after 6 or 72
      h. IFN-gamma led to a dose-dependent and time-dependent cytostatic inhibition of
      all six tumor cell lines; the renal carcinoma cells were by far the most
      sensitive, and with these, cytotoxic effects were also seen. The 50% inhibitory
      dose (ID50) for each cell line was different and remarkably constant over many
      months. When cells were exposed to IFN-gamma for only 9 or 72 h, those from three
      lines recovered completely from the growth inhibitory effects, but from three
      only partially. When cultured for several weeks in the presence of 1600 U/ml of
      IFN-gamma, two lines developed increased resistance to IFN-gamma, one became much
      less sensitive, and two showed no changes in sensitivity. We saw no correlations
      between these changes during continuous exposure to IFN-gamma and the
      antiproliferative ID50 for each cell or whether the cells recovered completely
      from the inhibitory effects of IFN-gamma after short-term exposure. Nevertheless,
      cells with a population doubling time of less than 48 h had low to moderate
      sensitivity to IFN-gamma and seemed to recover more completely than those
      doubling in more than 61 h. Our results indicate great individual variation in
      the in vitro sensitivity of carcinoma cells to the antiproliferative effects of
      IFN-gamma.

PMID- 7627804
TI  - Lectins inhibit the Aujeszky's disease virus-induced interferon-alpha production
      of porcine peripheral blood mononuclear cells.
AB  - The interaction between virus and peripheral blood mononuclear cells (PBMC)
      required to elicit the production of interferon-alpha (IFN-alpha) by the so
      called natural interferon-producing cell is unknown. However, results from
      inhibition experiments suggest that viral glycoproteins are essential in this IFN
      induction process. We demonstrate here that cellular glycoproteins also appear to
      be involved in the initiation of IFN-alpha production. Lectins, that is, sugar
      binding glycoproteins, inhibited the Aujeszky's disease virus-induced IFN-alpha
      production of porcine PBMC by up to 99%. The level of inhibition varied with
      lectin used (concanavalin A, Galanthus nivalis lectin, Helix pomatia lectin, and
      lentil lectin). Preincubation experiments with porcine cells and concanavalin A
      (ConA) revealed that the lectin exerted its major effect directly on the PBMC.
      Although the IFN-alpha production in some cases was reduced by more than 90%, the
      PBMC were still able to proliferate in response to mitogenic lectins. The ConA
      mediated inhibition of the IFN-alpha production was reduced if the lectin was
      added later than 6-8 h after the start of induction and was not mediated by
      soluble factors. Both orthovanadate and staurosporine inhibited the IFN-alpha
      production and did not relieve the ConA-mediated inhibition. Thus, ConA seems to
      interfere with the early events during IFN-alpha induction, but the mechanisms
      behind this interference could not be clarified.

PMID- 7627803
TI  - Absence of high-affinity binding sites for interferon alpha/beta in variant
      murine CD4+ T lymphocytes not expressing the T cell antigen receptor.
AB  - The T cell antigen receptor complex (CD3/Ti) plays a role in specific antigen
      recognition as well as in signal transduction, with its surface expression
      required for the function of several other structurally distinct receptor
      systems, including CD2, Ly-6(TAP), and Thy-1. In this communication, evidence is
      presented suggesting an association between the surface expression of CD3/Ti and
      that of the type 1 interferon (IFN) receptor in a CD4+ murine T cell clone. We
      tested the proliferative responses and their capacity to be inhibited by type 1
      IFN with the wild-type, CD3/Ti-positive T cell clone and its CD3/Ti-negative
      variants did not respond to specific antigen or anti-CD3 antibody stimulation but
      they did respond to T cell growth factor (TCGF), stimulation as did the wild-type
      parental cells. Therefore, the type 1 IFN inhibition of TCGF-stimulated
      proliferative responses of wild-type and variant cells were compared. Both
      natural and recombinant type 1 IFNs inhibited TCGF-induced tritiated thymidine
      (3H-TdR) incorporation in the wild-type T cell clone, with a ID50 of 60-80 U/ml.
      By contrast, the variants required much higher doses of type 1 IFN. The ID50 with
      natural murine IFN-beta was 10,000 U/ml, but this same dose of human IFN-alpha
      A/D gave only a marginal inhibitory effect. Accompanying the loss of IFN
      responsiveness, these variants also exhibited a loss of high-affinity type 1 IFN
      receptors. Taken together, these data suggest that the CD3/Ti complex plays a
      role in the surface expression of the type 1 IFN receptor in a CD4+ T cell
      clone.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7627805
TI  - Interferon-gamma receptor extracellular domain-IgG fusion protein produced in
      Chinese hamster ovary cells as mixture of glycoforms.
AB  - Glycosylation of proteins fulfills important functions and because of its
      diversity contributes to apparent protein heterogeneity. We investigated the
      heterogeneity of a fusion protein comprising the extracellular domain of the
      human interferon-gamma (IFN-gamma) receptor and parts of the human IgG3 constant
      region, a potential IFN-gamma antagonist. The protein was produced in Chinese
      hamster ovary (CHO) cells and was secreted into the culture medium as an 175 kD
      glycoprotein. Glycosylation represented approximately one-third of the apparent
      molecular mass of the fusion protein, consisted of N- and O-linked carbohydrate
      moieties, and included sialic acid residues as part of both N- and O-linked
      oligosaccharides. Fusion protein forms with different apparent molecular masses
      and charges were separated by ion-exchange chromatography. Preparative
      electrofocusing revealed a wide spectrum of glycoforms. Glycosylation of the
      fusion protein and of soluble IFN-gamma receptors, comprising the extracellular
      domain of the native sequence, expressed in insect and CHO cells did not
      interfere with affinity of ligand binding.

PMID- 7627806
TI  - Type 1 interferon as an antiinflammatory agent: inhibition of lipopolysaccharide
      induced interleukin-1 beta and induction of interleukin-1 receptor antagonist.
AB  - The effect of two type 1 interferons (r-metIFN-con1 and IFN-alpha 2b) on the
      induction of specific cytokines and IL-1Ra in whole blood was examined. IFN-gamma
      was induced at low levels following treatment of diluted whole blood in some but
      not all subjects. IL-1Ra was induced by both r-metIFN-con1 and IFN-alpha 2b, but
      with 10- to 100-fold higher induction per ng IFN with r-metIFN-con1 than with IFN
      alpha 2b. There was no detectable induction of TNF-alpha, IL-4, or IL-6 by either
      IFN. The effect of both IFN preparations was measured on LPS-induced inflammatory
      cytokines. Both IFN preparations inhibited the production of IL-1 beta when added
      to the diluted blood samples before LPS addition. However, neither IFN had any
      effect on IL-1 beta synthesis when added at the same time or after LPS induction.
      When added to total blood cells in the absence of LPS at low concentration (up to
      100 pg/ml), IFN slightly stimulated IL-1 beta production, but at 1000 pg/ml or
      greater there was significant inhibition of IL-1 beta production. These results
      suggest that type I IFNs play a role in regulating the inflammatory response.

PMID- 7627807
TI  - Effect of interferon-gamma on the expression of transforming growth factor-beta
      by human corneal fibroblasts: role in corneal immunoseclusion.
AB  - Human corneal fibroblasts (HCF) inhibit T cell alloresponse in mixed leukocyte
      response-human corneal fibroblast coculture. The inhibition is contact
      independent, insensitive to indomethacin, and is enhanced by pretreatment of HCF
      with interferon-gamma (IFN-gamma). To investigate cytokine-dependent mechanisms
      of inhibition of T cell alloresponse by HCF, the capacity of cultured HCF to
      produce transforming growth factor-beta (TGF-beta) and the modulatory role of IFN
      gamma on their TGF-beta production were investigated by radioreceptor binding
      inhibition assay (RRA) and the standard mink cell bioassay (BIA). The net total
      TGF-beta concentration of 4 day culture supernatants from IFN-gamma-treated HCF,
      measured by RRA, was 11.5 ng/ml. The net total bioactive TGF-beta concentrations
      of 4 day culture supernatants from HCF, before and after treatment with IFN
      gamma, measured by BIA, were 2.0 and 4.8 ng/ml, respectively. These findings
      indicate that HCF produce TGF-beta and increase their TGF-beta output under the
      influence of the proinflammatory cytokine IFN-gamma. Media-borne TGF-beta binding
      proteins appeared to be primarily responsible for the discrepancy between the TGF
      beta values measured by RRA and BIA. Active exclusion of TGF-beta binding
      proteins from intraocular fluids may have an important role in the maintenance of
      TGF-beta-dependent ocular immune privilege. Corneal fibroblasts may utilize TGF
      beta-dependent mechanisms to maintain the immunosecluded environment of the
      cornea and to preserve the homeostasis of corneal optical competency. Interferon
      gamma may enhance corneal immunoseclusion by upregulating the TGF-beta output of
      the corneal fibroblasts.

PMID- 7627809
TI  - Interferon-alpha 2 variants in the human genome.
AB  - Variants of human leukocyte interferon alpha 2 (IFN-alpha 2a, alpha 2b, and alpha
      2c) differ from each other by changes in their coding regions at nucleotide
      positions 137 and 170. As a result of these nucleotide variations, the DNA
      sequences of the three variants can be distinguished by selective restriction
      enzyme analysis. Human genomic DNA obtained from over 28,000 normal healthy
      individuals was used as templates in the polymerase chain reaction (PCR) to
      amplify the human IFN-alpha 2 gene sequence. The resulting PCR products were
      analyzed with restriction nucleases to identify the specific IFN-alpha 2 variant
      sequences present in the genomic DNA of the population examined. The results show
      that IFN-alpha 2b was detected as the predominant species and IFN-alpha 2c as a
      very minor species (< 0.1%). The IFN-alpha 2a gene was not detected in this
      population.

PMID- 7627808
TI  - Interleukin-1 production in tumor cells of human melanoma surgical specimens.
AB  - To determine whether IL-1 alpha and/or IL-1 beta protein is expressed by human
      melanoma tumor in vivo, we first analyzed nine human melanoma cell lines and
      optimized the in situ detection of these proteins. Three of the melanoma cell
      lines stained positively for both IL-1 alpha and IL-1 beta using
      immunohistochemistry (IHC). THe specificity of IHC was confirmed by the ability
      of purified recombinant IL-1 alpha and IL-1 beta protein to abolish the staining
      after being adsorbed by their respective antibodies before use in IHC. The three
      positively staining cell lines were also the only lines to demonstrate IL-1
      production by western blot analysis as well as IL-1 secretion by ELISA. Next we
      examined 29 surgically obtained melanoma tumor specimens (6 primary and 23
      metastases) that had been formalin fixed and paraffin embedded. Using the same
      anti-IL-1 antibodies, 5 of 23 metastatic tumors stained positively. None of the 6
      primary lesions stained for either IL-1 alpha or IL-1 beta. Comparison of
      staining pattern performed on serially sectioned tissue using preimmune serum and
      antibodies against S-100 protein, melanoma-associated antigen (HMB-45), and CD68
      (kappa P1), which recognizes monocyte-macrophage cell lineage, demonstrates for
      the first time that IL-1 protein is produced by human melanoma tumor cells in
      vivo. These findings provide the basis for examination of what may be a
      previously unrecognized biologically distinct subset of patients.

PMID- 7627810
TI  - A mouse placental immunoregulatory factor different from transforming growth
      factor beta.
AB  - Of the growth-promoting factors, transforming growth factor beta (TGF-beta) has
      been most clearly shown to act as a potent regulator of inflammation and
      immunity. It is highly suppressive for T and B lymphocyte proliferation,
      cytotoxic T lymphocyte generation, and lymphokine-activated killer cell
      development, as well as natural killer cell activity. Moreover, there is
      accumulating evidence that TGF-beta also may contribute to impaired immune
      surveillance of tumor development. In previous work, we isolated and described a
      40 kD glycoprotein extracted from mouse placenta. This placental factor (PF) is
      also a potent immune modulator in vivo: it is highly inhibitory of secondary
      antibody responses as well as cellular responses, such as local graft-versus-host
      reactions. Because placenta has been shown to be a major source of TGF-beta and
      several reports have indicated an important role for TGF-beta in the
      immunosuppressive mechanisms taking place during the course of mammalian
      gestation, we have looked for the presence of TGF-beta in our placental factor
      preparations. Our results clearly indicate that they do not contain TGF-beta or
      TGF-beta-like molecules by the following criteria: (1) no inhibition of Mv-1 Lu
      cell proliferation at any dose tested; (2) no band detected by immunoblotting
      using different polyclonal reagents specific for TGF-beta 1; and (3) no activity
      retained on or eluted from an affinity column made of immobilized monoclonal
      antibody against TGF-beta 2. Aliquots of the same preparations retained their
      full immune inhibitory capacity in vivo throughout the various assays.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7627811
TI  - Differential role of interferon-gamma in the potentiating effect of muramyl
      peptides for enhanced responses to lipopolysaccharide in mice: effect of
      cyclosporin A.
AB  - Cyclosporin A (CsA) administration reduced mortality in mice sensitized to
      endotoxic toxicity by various agents, such as muramyl dipeptide (MDP) or a
      lipophilic derivative. CsA is an inhibitor of a variety of T cell responses,
      suggesting that muramyl peptides could influence LPS-induced effects via the
      release of lymphokine. The potentiation of TNF production by pretreatment with
      muramyl peptides was comparable in nude mice and in controls, indicating that it
      is a T-independent mechanism, and CsA produced a similar inhibition in both
      groups. Neutralizing antibody to IFN-gamma did not change the elevated TNF level
      obtained in the blood when LPS was given after a muramyl peptide. However, the
      same treatment with anti-IFN-gamma MAb prevented the death of mice challenged
      with LPS plus MDP or plus a lipophilic derivative displaying similar effects. In
      comparing three selected muramyl peptides, we also show that the priming effect
      could be dissociated from the toxic synergism with LPS.

PMID- 7627812
TI  - Effects of tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 on
      type I iodothyronine 5'-deiodination in rat thyroid cell line, FRTL-5.
AB  - Using a functioning rat thyroid cell line (FRTL-5), we studied the effects of
      tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and
      interleukin-6 (IL-6) on thyroidal type I iodothyronine 5'-deiodination (I-5'
      deiodination) and on the expression of I-5'-deiodinase (I-5'-D) mRNA. After 24 h
      incubation in medium containing 0.5 microM rT3 with a tracer amount of [125I]rT3,
      radioactivity of released 125I- was counted. Deiodination in live FRTL-5 cells
      was enhanced about three times from the basal level by the addition of TSH and
      was inhibited markedly by propylthiouracil and dose dependently by T4. These
      results suggest the suitability of this model for investigating I-5'-deiodination
      in live thyroid tissue. Basal and TSH-induced I-5'-deiodination were
      significantly inhibited by 100 ng/liter of IL-1 beta and IL-6, and the inhibitory
      effect of TNF-alpha was seen over 1 microgram/liter. I-5'-deiodination was
      restored by removal of the cytokines. TSH-induced cAMP production and (Bu)2cAMP
      induced I-5'-deiodination were also inhibited by the cytokines. Catalase,
      dexamethasone, and indomethacin did not abolish the inhibitory effects of the
      cytokines. Reverse transcriptase-polymerase chain reaction (RT-PCR) revealed a
      marked suppression of I-5'-D mRNA expression by IL-1 beta and IL-6. We conclude
      that these cytokines inhibit the thyroidal type I I-5'-deiodination in the order
      of potency IL-1 beta > IL-6 >> TNF-alpha, probably by decreasing the I-5'-D mRNA
      level.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7627813
TI  - Administration of recombinant interleukin-12 to mice suppresses hematopoiesis in
      the bone marrow but enhances hematopoiesis in the spleen.
AB  - Although IL-12 has been reported to synergize with c-kit ligand (KL) in promoting
      hematopoietic stem cell proliferation in vitro, administration of recombinant
      mouse IL-12 (rIL-12) to normal mice caused a dose- and time-dependent anemia,
      leukopenia, and thrombocytopenia in vivo. Decreased numbers of bone marrow cells
      were recovered from the tibiae of IL-12-treated mice, and histologic examination
      of the marrow revealed a loss of mature neutrophils and red blood cell
      precursors. However, simultaneously with the suppression of hematopoiesis in the
      bone marrow, the IL-12-treated mice developed splenomegaly, which was largely
      caused by a marked enhancement of splenic extramedullary hematopoiesis of the
      erythroid, myeloid, and megakaryocytic lineages. These histologic observations
      were confirmed by colony-forming cell assays in which administration of IL-12 was
      shown to cause a time-dependent decrease in bone marrow CFU-GM, CFU-E, and BFU-E
      hematopoietic colony-forming cells while causing an increase in splenic CFU-GM
      and BFU-E colony-forming cells. All these effects were reversible upon cessation
      of IL-12 treatment. The observation that in IL-12-treated mice hematopoiesis was
      suppressed in the marrow but enhanced in the spleen suggests that
      myelosuppression was not caused by a direct effect of IL-12 on hematopoietic
      progenitors. It seems likely that myelosuppression was caused instead by an IL-12
      induced alteration in the local environment of the marrow.

PMID- 7627816
TI  - Highly efficient retroviral gene transfer into human primary T lymphocytes
      derived from peripheral blood.
AB  - T lymphocytes are a promising cell vehicle for gene therapy purposes. By
      cocultivating retroviral vector producing cells and target cells, highly
      efficient gene transfer was achieved with activated human T lymphocytes derived
      from peripheral blood with vectors carrying different forms of the bacterial beta
      galactosidase gene including the regular LacZ gene, the Sh-ble::LacZ gene and the
      nlsLacZ gene. Infection kinetics of T cells activated by a combination of
      monoclonal antibodies directed against CD2 and CD28 indicated that the highest
      efficiencies of transduction were obtained when the cocultivation began 4 days
      after stimulation. In fact, with the FLac vector, a new retroviral vector which
      expresses the Sh-ble::LacZ gene, we observed up to 78% transduction efficiency
      assessed by X-gal staining performed 2 days after the end of the cocultivation.
      Expression of the transduced genes was observed throughout the period of culture.
      Neither the cocultivation step nor the expression of the transduced Sh-ble::LacZ
      gene altered cell culture proliferation or the expression of selected cell
      surface antigens. In addition, we showed that CD4+ and CD8+ T cells were equally
      transduced.

PMID- 7627815
TI  - Immunomodulatory effects of human neuroblastoma cells transduced with a
      retroviral vector encoding interleukin-2.
AB  - We have investigated whether retroviral mediated transfer of the IL-2 gene
      renders human neuroblastoma cells immunogenic, justifying their use in a clinical
      tumor immunization study. Fourteen neuroblastoma cell lines were established from
      patients with disseminated neuroblastoma and transduced with the vector G1Ncvl2,
      which contains the neomycin phosphotransferase gene and the cDNA of the human
      interleukin-2 gene. Clones secreting > 150 pg/10(6) cells/24 h of IL-2 were
      selected for further study. Secretion of IL-2 was maintained for at least 3 weeks
      in nonselective media, implying that production of the cytokine would continue
      under in vivo conditions. Co-culture of IL-2 transduced cell lines with patient
      lymphocytes induced potent cytotoxic activity against both transduced and
      parental neuroblastoma cell lines. This activity was HLA unrestricted, and
      predominantly mediated by CD16+ or CD56+ and CD8- lymphocytes. These data form
      the preclinical justification for our current immunization protocol for patients
      with relapsed or resistant neuroblastoma.

PMID- 7627814
TI  - Optimization of methods to achieve mRNA-mediated transfection of tumor cells in
      vitro and in vivo employing cationic liposome vectors.
AB  - Direct in vivo transfection of tumor nodules in situ via liposome-DNA complexes
      has been employed as a strategy to accomplish antitumor immunization. To
      circumvent the potential safety hazards associated with systemic localization of
      delivered DNA, the utility of mRNA transcript-mediated gene delivery was
      explored. Capped, polyadenylated mRNA transcripts encoding the firefly luciferase
      and Escherichia coli lacZ reporter genes were derived by in vitro transcription.
      Transfection of the human breast cancer cell line MDA-MB-435 in vitro was
      accomplished employing cationic liposome-mRNA complexes. Evaluation of a panel of
      cationic liposome preparations demonstrated significant differences in the
      capacity of the various preparations to accomplish mRNA-mediated transfection.
      Quantitative evaluation of in vitro transfection demonstrated that target cells
      could be transfected at a high level of efficiency. The mRNA liposome-complexes
      were evaluated for in vivo transfection of tumor nodules in human xenografts in
      athymic nude mice. It could be demonstrated the liposome-mRNA complexes were
      comparable in efficacy to liposome-DNA complexes in accomplishing in situ tumor
      transfection. Thus, mRNA may be considered as an alternative to plasmid DNA as a
      gene transfer vector for genetic immunopotentiation applications.

PMID- 7627817
TI  - Ribozyme-mediated in vitro cleavage of transcripts arising from the major
      transforming genes of human papillomavirus type 16.
AB  - Human papillomaviruses (HPV) have been strongly implicated as important cofactors
      in the development of several human malignancies, particularly anogenital
      carcinomas. Products arising from the E6 and E7 open reading frames (ORFs) from
      HPV-16, a type commonly associated with human cervical carcinoma, are essential
      for viral transformation. Unfortunately, a highly effective treatment for this
      infection is not available. To develop a novel treatment for this disease,
      ribozymes were designed to cleave all transcripts encoding HPV-16 E6 and E7 ORFs
      in proximity to their translational start sites ("AUG"). Cleavage sites for Rz110
      and Rz558 occur immediately 3' to nucleotides 110 and 558 of the viral genomic
      DNA, respectively. Oligonucleotides corresponding to these ribozymes were
      synthesized and inserted into a eucaryotic viral vector derived from the
      nonpathogenic parvovirus, adeno-associated virus. Ribozyme transcription from
      this vector, termed CWRT7:SVN, is under control of both the highly active Rous
      sarcoma virus long terminal repeat and bacteriophage T7 promoters. T7 transcripts
      of the E6 and E7 ribozymes efficiently cleaved their cognate targets in vitro
      under a variety of conditions, including physiological temperature. These results
      may provide the basis for the development of a ribozyme-based, gene therapeutic
      treatment for HPV-associated diseases.

PMID- 7627818
TI  - 3rd International Conference on Gene Therapy of Cancer. San Diego, California,
      November 10-12, 1994. Abstracts.

PMID- 7627819
TI  - [Changes in the small intestine mucosa in chronic alcoholism].
AB  - Morphologic and enzyme induction phenomena changes in the small bowel mucosa
      produced by excessive alcohol intake were studied. Both aspects may have
      nutritional repercussions in alcoholic patients. Three groups of patients were
      included in the study: group I made up of 20 healthy controls, group II with 30
      alcoholic patients with active alcohol intake at the time of the study and group
      III made up of 30 alcoholics following abstinence. The nutritional status,
      possible existence of associated liver disease, intestinal morphology and the
      mucosal and serum gamma glutamyltranspeptidase (GGT) levels were evaluated. The
      morphologic changes observed under the study conditions, with normal levels of
      ingestion in alcoholic with active alcohol intake, were mild and could be related
      with the nutritional status and folate deficiency which some presented than being
      secondary to a direct toxic effect of the alcohol. Moreover, significant
      increases were observed in the GGT in the intestinal mucosa of alcoholics with
      active intake (3.97 +/- 1.37 mU/g of tissue) with respect to the control group
      (1.86 +/- 0.7 mU/g). The changes were rapidly reversible following abstinence and
      correlated with the changes observed in serum, thus suggesting an enzymatic
      induction mechanism.

PMID- 7627820
TI  - [Are there clinical differences between typical and vigorous achalasia and
      response to pneumatic dilatation?].
AB  - The aim of this study was to analyze whether the vigorous character of esophageal
      contraction conditions differences in the clinical characteristics or in response
      to pneumatic dilatation treatment in patients with achalasia. To do so, a
      prospective protocol study was designed in which the clinical, radiological, and
      manometric characteristics of the patients and the response to pneumatic
      dilatation were compared on the basis of the presence or absence of severe
      contraction of the esophageal body. One hundred fifty-seven consecutive patients
      diagnosed with achalasia were included on presentation of a compatible clinical
      picture and absence of peristalsis in the esophageal body. Out of these patients,
      120 presented a manometric pattern of typical achalasia and 37 had vigorous
      achalasia. Response to pneumatic dilatation was analyzed in 116 patients, 90 with
      typical achalasia and 26 with vigorous achalasia. Significant differences were
      only found between the two groups with respect to the greater response tone of
      the lower esophageal sphincter observed in the patients with vigorous achalasia.
      There were no differences in the remaining clinical, radiologic or manometric
      variables compared. Neither were any differences observed in regard to
      therapeutic response to pneumatic dilatation in the two groups of patients. It
      may be concluded that differentiation between typical and vigorous achalasia has
      no clinical or therapeutic significance.

PMID- 7627821
TI  - [Increase of gamma-glutamyltranspeptidase in patients with compensated
      hypoalphalipoproteinemia and type IIa dyslipidemias].
AB  - Twenty-one asymptomatic patients presenting isolated elevations of gamma
      glutamyltranspeptidase (GGT) were studied over the previous 10 years with all the
      findings being accidental. No other analytical alterations were demonstrated.
      Ingestion of alcohol, drugs or another type of toxic substance, diabetes,
      neurologic disease or neoplasm were discarded. Echography of the liver and the
      biliary tract was normal. In the first nine patients studied, liver biopsy was
      performed being normal or with minimum unspecific alterations. In two patients
      endoscopic retrograde cholangiography was carried out with no alterations being
      observed. Lipid study was performed in all the patients with alpha
      hypolipoproteinemia being found in 15 patients, compensated type II lipid profile
      in 5 and a normal lipid profile in one. To the author's knowledge there have been
      no reports of this lipid disorder causing elevations in GGT. However, on being
      the only abnormality found in these patients the authors believe that this may be
      the cause although the mechanism is unknown.

PMID- 7627822
TI  - [Melanoma of the small intestine and adenocarcinoma of the colon].
AB  - The clinical case of a 73-years old male who was admitted for diarrhea and loss
      of weight is presented. Barium enema and colonoscopy demonstrated small size
      polyps in the sigmoid colon, one of which had a histologic diagnosis of
      adenocarcinoma. Abdominal examination detected a mass in the mesohypogastrium
      which did not appear to be related to the previous findings. CAT and intestinal
      transit confirmed a second tumor in the small bowel with the histologic diagnosis
      of a resected specimen being melanoma.

PMID- 7627823
TI  - [Ischemic colitis as manifestation of Takayasu arteritis].
AB  - The case of a 44-years old patient who developed two episodes of ischemic colitis
      over a three year interval and completely recovering from the same with
      conservative treatment is presented. The patient was symptomatic only during the
      acute episodes. Arteriographic study performed during the second episode showed
      stenosis of the infrarenal aorta reducing the blood flow by more than 50%
      facilitating to the development of arterial thrombosis at the origin of the
      inferior mesenteric artery. These arteriographic findings, together with other
      stenoses in the descending, superior mesenteric, and left subclavian thoracic
      aorta arteries led to the diagnosis of Takayasu arteritis. Despite the lack of
      general symptomatology of the disease, the patient was posteriorly administered
      steroid treatment with the aim of reducing the local inflammatory process and the
      risk of new thrombotic episodes.

PMID- 7627824
TI  - [Symptomatic primary biliary stenosis without cholestasis].
AB  - The case of a 59-years old patient with typical clinical manifestations of
      primary biliary cirrhosis (PBC): pruritus, asthenia, arthralgias and dry
      syndrome, with skin pigmentation and AMA positivity, hypergammaglobulinemia and
      an elevation of IgM is presented. Liver biopsy was compatible with stage II PBC.
      No analytical data of cholestasis, has been seen over 26 months of follow up with
      normal transaminases, alkaline phosphatase, gamma-glutamyltranspeptidase and
      cholesterol. The absence of cholestasis in the presence of symptoms is of
      interest.

PMID- 7627825
TI  - [Hepatocellular carcinoma and liver transplantation].

PMID- 7627826
TI  - [Barrett esophagus: from metaplasia to adenocarcinoma].

PMID- 7627827
TI  - [Percutaneous fine-needle transhepatic cholangiography: 20 years later].

PMID- 7627828
TI  - [Chronic diarrhea and ticlopidine].

PMID- 7627829
TI  - [Carcinoma of the spleen].

PMID- 7627830
TI  - [Diagnostic value of upper abdominal pain in HELLP syndrome].

PMID- 7627831
TI  - Recent advances in the molecular genetics of urogenital tumors.

PMID- 7627832
TI  - Phentolamine test for operative complications of pheochromocytoma: its prognostic
      importance.
AB  - The purpose of this investigation was to assess whether the phentolamine test is
      able to predict blood pressure fluctuations during operations on patients with
      pheochromocytoma. We administered 5 mg phentolamine intravenously to 11 patients
      with pheochromocytoma and 6 patients with essential hypertension, pretreated with
      alpha-adrenoceptor antagonists. Plasma concentrations of epinephrine and
      norepinephrine were determined before and after phentolamine administration, and
      blood pressure was measured repeatedly. Subsequently, all patients with
      pheochromocytoma underwent adrenal operations. Evidence is presented to show
      that: (1) in patients with pheochromocytoma whose blood pressure remains stable
      during their operation, phentolamine produces no clear effects on mean blood
      pressure (MBP), plasma epinephrine and plasma norepinephrine except in one
      patient with Sipple's syndrome, (2) in patients with pheochromocytoma exhibiting
      unstable blood pressure changes during surgery, phentolamine lowers MBP and
      raises plasma norepinephrine and (3) in patients with essential hypertension, MBP
      and plasma catecholamines remain unchanged following phentolamine administration.
      Based on these findings, this pharmacological test appears to be useful for
      predicting hemodynamic stability in patients with pheochromocytoma pretreated
      with alpha-adrenoceptor antagonists.

PMID- 7627833
TI  - Experimental study of microwave coagulation of a VX-2 carcinoma implanted in
      rabbit kidney.
AB  - This paper describes the results of an experimental study of the microwave
      coagulation of VX-2 renal tumors implanted in rabbits. The rabbits undergoing
      microwave treatment exhibited a satisfactory survival rate and a complete
      response to treatment, as verified by histological examination. All the rabbits
      receiving no treatment died within 6 weeks of implantation of the VX-2 carcinoma.
      These results indicate that microwave coagulation may be a curative method of
      treatment for a relatively small renal tumor. Intraoperative real-time ultrasonic
      scanning permits the percutaneous microwave coagulation of renal cancer in a
      clinical situation.

PMID- 7627834
TI  - Effect of immunosuppression on the urinary excretion of BK and JC polyomaviruses
      in renal allograft recipients.
AB  - Sixty-five renal allograft recipients on immunosuppressive therapy were examined
      for BK and JC viruria using Southern blot hybridization. The incidence and degree
      of BK and JC viruria were compared between this population (group RTR) and, an
      age- and sex-matched population of non-immunosuppressed individuals (group CTR).
      In the results, the incidence of BK viruria was significantly increased in the
      RTR group compared with the CTR group, while that of JC viruria was similar in
      the 2 groups. The proportion with a high level of JC viruria, however, was
      greater in the RTR group compared with the CTR group. Additionally, it was also
      demonstrated that the incidence of both BK and JC viruria was not affected by the
      characteristics of renal transplant recipients, such as differences in the donor
      source (living-related vs cadaveric), type of immunosuppressive agents used, or
      the time post-transplantation.

PMID- 7627835
TI  - A new tumor marker for bladder cancer.
AB  - Biochemical assay and immunohistochemical staining of neutral endopeptidase were
      performed on bladder cancer cells. In superficial bladder cancer the enzyme
      activity and immunohistochemical intensity of staining were high, while invasive
      bladder cancer showed only a low level of activity. This finding suggests that
      neutral endopeptidase is expressed at a certain stage of cell differentiation,
      during the neoplastic process in the bladder. Gene expression is assumed to be
      closely correlated with this mechanism. From the results of this study neutral
      endopeptidase will serve as a new tumor marker for bladder cancer as well as
      acute lymphatic leukemia.

PMID- 7627836
TI  - A new scoring system based on the histological behavior and proliferative
      activity of tumor cells for grading the malignant potential of bladder cancers.
AB  - Urothelial cancer can be considered to consist of a spectrum of diseases with
      diverse natural histories and the conventional morphological classifications
      provided by classical histology remain the basis for any decision-making process.
      The proliferative rate of the tumor cells may be significant since the rate of
      DNA synthesis is directly related to the rate of tumor growth or tumor
      involvement. We have previously reported that flow cytometric deoxyribonucleic
      acid (DNA)/bromodeoxyuridine (BrdU) bivariate analysis can provide important
      information about the malignant potential of bladder cancer. In the present
      study, we have formulated a new system based on the histological grade and tumor
      proliferative activity determined by the BrdU labeling index. An attempt has been
      made, moreover, to investigate whether this grading system can be used to
      determine the malignant potential of bladder cancers. A total of 86 patients with
      bladder tumors, histologically proven to be transitional cell carcinomas, were
      analyzed. Immediately after removal of tumor specimens, in vitro BrdU labeling
      was performed. Multivariate survival analysis was conducted using Cox's
      regression model, followed by estimation of the risk ratio for survival. Based on
      the risk ratio of the histological grade and the BrdU labeling index, a score
      ranging from 1 to 52 was assigned to each tumor. Forty-four patients with a score
      of 1 had a 100% survival rate at 3 years, compared with 42.9% for patients having
      a score greater than 1. Conversely, 26 patients with the highest score, 52
      exhibited a survival rate of only 17.3% at 3 years.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7627837
TI  - Correlation of p53 protein expression in human urothelial transitional cell
      cancers with malignant potential and patient survival.
AB  - The p53 gene product has been detected frequently in various human malignancies.
      We have studied the expression of p53 protein in urothelial transitional cell
      cancers (TCCs) and examined its correlation with pathologic grade, stage(pT) and
      patient survival. Specimens from 69 surgically-resected TCCs (38 cases of urinary
      bladder cancer, 17 cases of ureteral cancer and 14 cases of renal pelvic cancer)
      were examined by immunohistochemical staining, using two anti-p53 monoclonal
      antibodies, PAb1801 and PAb240, and a polyclonal antibody, CM-1. Twenty-six TCCs
      (37.6%) were positively stained by at least one of the three antibodies.
      Statistical analysis showed a significant correlation between p53 expression and
      high pathologic grade (p < 0.05, p < 0.001) or progressive pathologic stage (p <
      0.01). In addition, in 51 of the patients who were available for follow-up (23
      cases of urinary bladder cancer, 13 cases of ureteral cancer, and 15 cases of
      renal pelvic cancer), the correlation between p53 protein expression and
      prognosis was examined. The survival of patients exhibiting positive p53 protein
      expression was significantly worse than those with p53-negative tumors (p <
      0.05). These results suggest that an immunohistochemical test for p53 protein may
      be a useful method of evaluating the malignant potential of TCCs. Additionally,
      expression of p53 protein in TCCs is an indicator of a poor prognosis which
      should be considered in drawing up treatment strategies.

PMID- 7627838
TI  - In vitro enhancement of natural killer cell activity by BCG and the antagonistic
      inhibition of the susceptibility of K562 cells to lysis by peripheral blood
      lymphocytes in patients with urinary bladder tumor.
AB  - The effect of bacillus Calmette-Guerin (BCG) on the natural killer (NK) activity
      of peripheral blood lymphocytes (PBL) and the susceptibility of K562 cells to
      lysis by PBL in patients with urinary bladder tumors (UBT) was evaluated using a
      4-h 51Cr release assay. The addition of BCG 0.1-1 mg/ml to the assay increased NK
      activity. In contrast, BCG at higher concentrations (10 mg/ml) reduced NK
      activity. This effect of BCG was also observed in healthy donors. Pretreatment of
      PBL with BCG 0.1-1 mg/ml also resulted in increased NK activity, while higher
      concentrations of BCG depressed it. Treatment of K562 cells with BCG 1-10 mg/ml
      for 3 hours reduced their susceptibility to lysis by PBL. Kinetic studies showed
      that the reduced susceptibility became apparent 3 hours after initiation of
      culture of K562 cells with BCG and lasted 12 hours. The susceptibility of BCG
      treated K562 cells to lysis by purified NK cells and lymphokine activated killer
      (LAK) cells was also reduced. Both live and dead BCG exerted an inhibitory effect
      on the target cells. The effector-to-target binding assay demonstrated that
      treatment with BCG reduced the number of PBL conjugates with K562 cells. These
      results indicate that BCG increases the NK activity of PBL, while rendering K562
      cells resistant to PBL lysis by inhibiting the effector-to-target binding. BCG at
      lower concentrations (0.1-1 mg/ml) may be useful in patients with UBT. The
      possible mechanisms responsible for the effects of BCG on K562 cells and their
      possible clinical implications are discussed.

PMID- 7627839
TI  - The augmented rectal bladder for urinary diversion: experience with the original
      valved rectum and a valve-less modification.
AB  - Kock's augmented and valved rectum was created in 10 patients following total
      cystectomy. During an observation period of up to 46 months, 4 patients died (1
      from a recurrence of cancer, 1 from multiple organ failure subsequent to diabetes
      mellitus, 1 from coronary insufficiency, and 1 from cerebral hemorrhage). Post
      operative complications included valve failure in 1, hydronephrosis in 2, and
      mild nocturnal urinary incontinence in another. Hyperchloremic metabolic acidosis
      was particularly notable in the cases without an intussuceptive valve of the
      rectum. Their base excess ranged from -6.9 to -15.0 mM/l but the condition was
      satisfactorily controlled by oral administration of alkaline agents. Although the
      present method has a number of shortcomings, the absence of a stoma and
      elimination of the need for self-catheterization are outstanding benefits. For
      these reasons, we believe that it is an effective option for urinary diversion.

PMID- 7627840
TI  - Laparoscopic varicocelectomy: invasiveness and effectiveness compared with
      conventional open retroperitoneal high ligation.
AB  - The invasiveness of laparoscopic varicocelectomy and open retroperitoneal high
      ligation of the internal spermatic veins were compared and the surgical effects
      on fertility of these two procedures determined. 48 of 97 men diagnosed with
      varicocele testis underwent laparoscopic varicocelectomy, while the remaining 49
      underwent open retroperitoneal high ligation of the internal spermatic vessels.
      Operating time, number of post-operative days to walking, length of hospital stay
      and analgesic use were measured as peri-operative indicators of invasiveness. In
      addition, seminal parameters were determined in order to evaluate the effects of
      these procedures on fertility. The operating time required for laparoscopic
      surgery was significantly longer than that for open surgery (96.6 vs 78.1 min., p
      = 0.0078). The patients in the laparoscopic surgery group began walking earlier
      post-operatively than did those who underwent open high ligation (0.97 vs 1.42
      days, p = 0.00037). Length of hospital stay for the laparoscopic patients was
      shorter than for the open surgery group (7.05 vs 9.55 days, p = 0.00001). There
      were no statistical differences between the groups in terms of semen quality or
      improvement in the post-operative rate of pregnancy of partners. These findings
      indicate that laparoscopic varicocelectomy is associated with a shorter period of
      convalescence than open high ligation of the internal spermatic vessels.

PMID- 7627841
TI  - Inhibitory effects of bestrabucil, a conjugate of chlorambucil and estradiol, on
      the production of androgen-induced growth factor(s) by Shionogi carcinoma 115
      cells.
AB  - It is known that diffusible trophic factors play an important role in both the
      normal and cancerous growth regulatory processes of hormone-responsive cells such
      as are found in the prostate and mammary glands. Consequently, it is important to
      identify whether the production of such growth factors is affected by
      administration of therapeutic agents. We examined the effect of bestrabucil, a
      benzoate of an estradiol-chlorambucil conjugate, on the production of growth
      factor(s) by Shionogi carcinoma 115 (SC-115) cells, an androgen-responsive
      cultured cancer cell line. We then investigated whether the inhibitory effect
      found was specific to bestrabucil, or if it was also produced by a mixture of the
      2 compounds, estradiol and chlorambucil. Bioassay employing BALB/3T3 cells
      demonstrated the presence of two kinds of growth factor in the conditioned medium
      obtained by culturing SC-115 cells in medium containing 10(-8) M testosterone;
      these factors could be separated by heparin-sepharose column chromatography using
      0.5 M NaCl and 1.1 M NaCl. When the SC-115 cells were cultured in medium
      containing bestrabucil, at a concentration of 10(-5) M, no growth factor activity
      was detected in the fraction eluted from the heparin-sepharose column by 1.1 M
      NaCl. At bestrabucil concentrations of 10(-5)-10(-7) M, concentration-dependent
      inhibition of growth factor production by SC-115 cells could be demonstrated by
      3H-thymidine uptake assay. However, this inhibitory effect could not be
      demonstrated using only a mixture of estradiol and chlorambucil.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7627843
TI  - A pitfall in diagnosing a tumor thrombus by computed tomography.
AB  - This paper presents a case of right renal cell carcinoma with a false-positive
      finding of tumor thrombus in the inferior vena cava. The intraluminal filling
      defect revealed by computed tomography appeared to be an artifact due to the
      inflow of non-opacified blood into the inferior vena cava. The possibility of
      such an artifact should be borne in mind to avoid as far as possible any
      unnecessary diagnostic intervention and delay in instituting proper therapy.

PMID- 7627842
TI  - Urinary control after radical transurethral resection of the prostate in male
      paraplegics: urodynamic evaluation of its effectiveness in relieving
      incontinence.
AB  - We report our investigation of urinary incontinence in 51 male paraplegics with
      radical transurethral resection of the prostate. Pre-operatively, 28 cases
      (55.9%) had moderate or severe incontinence, which persisted post-operatively
      only in 21 cases (41.2%) and was less severe. Post-operatively, bladder
      compliance was improved from 22.1 +/- 22.6 ml/cmH2O to 36.4 +/- 38.5 ml/cmH2O,
      and the maximum pressure of uninhibited detrusor contraction was reduced from
      40.2 +/- 21.5 cmH2O to 18.3 +/- 19.0 cmH2O. These significant improvements are
      thought to contribute to the relief of urinary incontinence, regardless of the
      reduction in maximum urethral closure pressure.

PMID- 7627844
TI  - The aggressive treatment of choriocarcinoma of the testis associated with lung
      bone, and brain metastases.
AB  - A case of metastatic choriocarcinoma of the testis involving the retroperitoneum,
      lung, bone, and brain was successfully treated by surgery, chemotherapy and
      radiotherapy.

PMID- 7627845
TI  - Mullerian duct cyst with 46, XYq-.
AB  - We report a case of a mullerian duct cyst associated with a 46, XYq- chromosome
      anomaly. Mullerian duct cyst is a consequence of the abnormal regression of
      paramesonephric derivative. In the past many different manifestations have been
      associated with the 46, XYq-, anomaly. We discuss the possibility that a
      mullerian duct cyst may be one clinical manifestation of 46, XYq-.

PMID- 7627846
TI  - Epidemiology of urological cancer deaths in Japan.
AB  - We analyzed mortality data (1973-84) associated with 19 major cancers in Japan.
      The standardized mortality ratio (SMR) for prostate cancer was high in
      prefectures clustered in the Kanto-Chubu and Kyusyu regions, and that for renal
      cancer was high in prefectures scattered over eastern Japan. On the other hand,
      the SMR for prostate cancer was low in prefectures in the Kinki and Shikoku
      regions. In males, the SMR for bladder cancer was low in the Kanto and Chubu
      regions, and that for renal cancer was low in the Kanto-Chubu, Shikoku and Kyusyu
      regions. The correlation between the prefectural SMR for urological cancers and
      other cancers was analyzed. Pairs of cancers which were fairly highly correlated
      (0.5 or higher) were bladder-lung, kidney-colon, kidney-breast, kidney-ovary, and
      kidney-pancreas. For most cancers, the prefectural SMR in males was highly
      correlated (0.5 or higher) with that in females. However, for cancer of the bone,
      bladder, skin and larynx, the correlation coefficient was less than 0.5. In 14 of
      the 19 cancers examined, the slope of the logarithm of the age-specific mortality
      rate plotted against the logarithm of age was linear, and the relationship
      between age and mortality rate could be expressed by the formula Log M (mortality
      rate) varies; is directly proportional to nLog T (age) The value of "n"
      calculated using the formula ranged from 4 to 7 for most cancers, and was highest
      (9.5) for prostate cancer.

PMID- 7627847
TI  - Management and outcome of antenatally diagnosed hydronephrosis.
AB  - From March 1989 to December 1992, we encountered 25 kidneys in 21 patients with a
      suspicious ureteropelvic junction (UPJ) obstruction detected only on prenatal
      ultrasound. In all these patients other urological abnormalities were excluded by
      voiding cystourethrography and other radiological findings. Diuretic renography
      (DR) was initially performed at an age ranging from 15 days to 32 months in all
      patients and repeated a total of 39 times. Both the split renal function (SRF)
      and diuretic drainage half-time clearance (DT1/2) of radioagent were within their
      normal ranges in the case of 15 (60%) of the kidneys on initial DR. In these
      kidneys, there were no aggravated signs on repeated DR. Decreased SRF was found
      in 3 kidneys (12%) on initial DR. Of these, the renal function spontaneously
      reverted to normal in 2 cases with bilateral hydronephrosis. Another 1 kidney
      revealed significant UPJ obstruction assessed by pressure flow study and
      continuous nephrostomy drainage had brought relief from the obstruction 1 year
      later. Prolonged DT1/2 with normal SRF was found in 7 (28%) kidneys. The renal
      function did not deteriorate and the diuretic response improved on repeat DR
      except for 1 kidney, whose function deteriorated and on which ultimately,
      pyeloplasty was performed at 7 months of age. Prenatally diagnosed hydronephrosis
      is usually asymptomatic and clinically significant UPJ obstruction should be
      always verified. Although even today there is still no examination which can
      detect a definite obstruction, we can identify one as significant by careful
      repeat examinations and thus avoid unnecessary surgery without causing any renal
      deterioration.

PMID- 7627848
TI  - Basement membrane and carcinogenesis: ultrastructural observations in the
      basement membrane of the bladder epithelium in rats treated with N-butyl-N-(4
      hydroxybutyl)nitrosamine (BBN).
AB  - This study investigated the structural alterations in the basement membrane (BM)
      of the bladder epithelium in rats treated with N-butyl-N-(4
      hydroxybutyl)nitrosamine (BBN) using transmission electron microscopy. Following
      administration of BBN, thickening of the BM of the bladder epithelium was
      observed and remained almost constant from 4 to 20 weeks, although the
      pathological changes in the rat bladder epithelium induced by BBN altered over
      the same period of 20 weeks. The reason for this phenomenon can be explained by
      the increased interfacial area between the basal epithelial cells and the BM of
      the rat bladder epithelium due to an increase in the number and size of the
      microvilli on the basal cell surfaces adjacent to the BM. Our results also showed
      that the frequency of hemidesmosomes increased progressively during the period of
      carcinogenesis, especially in the lesions of noninvasive transitional cell
      carcinoma (TCC) in the rat bladder. It is suggested that the neosynthesis of BM
      components can be carried out both by benign hyperplastic cells and by
      noninvasive TCC cells of rat bladder. The alterations in the BM thickness may be
      affected by the changes in the number and size of the microvilli occurring on the
      basal cell surfaces adjacent to the BM. Both an increased frequency of
      hemidesmosomes and the neosynthesis of BM are closely related to cell
      proliferation during carcinogenesis.

PMID- 7627849
TI  - Over-expression of metallothionein and drug-resistance in bladder cancer.
AB  - Metallothionein (MT) in tumor cells has been implicated as one of the factors
      involved in mechanisms of resistance to anti-cancer drugs, including cis
      diaminedichroloplatinum (CDDP) and adriamycin (ADM). The relationship between the
      expression of MT and chemotherapy with anti-cancer drugs was studied in CDDP- and
      ADM-resistant human bladder cancer cell lines and tissue samples from clinical
      cases. In drug-resistant cell lines (T-24/ADM, CI-7/CDDP) established in our
      laboratory, MT expression was studied by immunohistochemistry using the avidin
      biotin peroxidase complex (ABC) method and radioimmunoassay (RIA), using anti-MT
      antibody. In addition, other potential mechanisms of drug resistance, such as P
      glycoprotein expression were examined and the levels of reduced glutathione
      (GSH), oxidized glutathione (GSSG) and glutathione-S-transferase (GST) determined
      in these cell lines. The results of these investigations demonstrate that the
      expression of MT in resistant cell lines increased 2.1- and 2.5-fold when
      compared with parent cell lines (CI-7, T-24). GSH, GSSG and GST levels were
      unchanged and P-glycoprotein was not over-expressed. A total of 120 tissue
      samples from 35 clinical cases of bladder cancer, before and after chemotherapy,
      were stained for MT which was detected in 10 of the 35 cases before chemotherapy.
      The incidence of MT expression was significantly higher (p < 0.05) in cases with
      lower pathological tumor grades.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7627850
TI  - Morphological analysis of ileal grafting following ileocystoplasty in the rat: a
      kinetic and ultrastructural study of the intestinal epithelium.
AB  - Ileocystoplasty was performed in rats and the morphological and cell-kinetic
      changes occurring in the ileal grafts were determined at intervals up to 18
      months postoperatively. The intestinal mucosa underwent no progressive changes
      but included villous and avillous regions associated with crypts of various sizes
      at all time intervals. Newly appearing and densely packed epithelial cells,
      shaped like petals, were always present in the lower parts of the villi
      associated with crypts showing no elongation, but seldom present in those with
      elongated crypts in the villous mucosa. Bromodeoxyuridine studies showed that the
      petal-shaped cells interfered with cell migration. No petal-shaped cells were
      observed in avillous mucosa in which the rate of cell turnover depended on crypt
      size. Fine-structural changes in absorptive epithelial cells in both types of
      mucosa included features of prematurity or hypermaturity in the cytoplasm and
      close adherence to the basal portions of adjacent cells and to the basal lamina.
      These changes may possibly contribute to the prevention of reabsorption of urine.
      However, some of the mechanisms responsible for adherence of the basal parts
      might incidentally interfere with the normal cell kinetics of the intestinal
      epithelium, resulting in dense packing of cells and the formation of multiple
      types of mucosa in ileal grafts.

PMID- 7627851
TI  - Clinical experience of lower urinary tract reconstruction using a urethral Kock
      pouch.
AB  - The operative procedure used in the present series involved a nerve-sparing
      radical cystectomy, with anastomosis of the urethra using a pouch made of
      detubularized ileum. The 36 patients who underwent this operation were all male
      with an average age of 58. No deaths resulted from the operation. As far as late
      complications were concerned, malfunction of the antireflux nipple valve was
      noted in 1 patient and stenosis occurred between the urethra and pouch in 2. One
      patient was found to have multiple stones in the pouch and reservoir
      decompensation was recognized in 2. Thus, the late complication rate was 17%.
      There were no cases of total incontinence, but nocturnal incontinence appeared in
      11 out of 31 (35%). A total of 20 out of 25 patients (80%) recovered their
      erectile function during the postoperative follow-up period and the disease-free
      survival rate at 5 years was 78%. Therefore, the urethral Kock pouch combined
      with nerve-sparing cystectomy has proved to be a useful procedure as far as the
      quality of life is concerned.

PMID- 7627852
TI  - Radionuclide evaluation of the uretero-ileoceco-proctostomy (ileocecal rectal
      bladder).
AB  - Technetium 99m diethylenetriaminepentaacetic acid renoscintigraphy was applied to
      14 patients to obtain comprehensive information on the kidney and urinary tract
      12.6 +/- 8.8 months (mean +/- SD) after uretero-ileoceco-proctostomy (ileocecal
      rectal bladder) diversion. The total glomerular filtration rate (GFR) was within
      the normal range in all patients, and the diuretic renogram was normal in 19 of
      28 kidneys, dilated-nonobstructive in 7 and obstructive-intermediate in 2. The
      mean colonic reflux was 16.6 +/- 18.4% of total excretion and the mean total
      residual in the colon and rectum was 38.8 +/- 15.5%. In the second study,
      performed 12.4 +/- 3.5 months later in 9 patients, the GFR of bilateral and
      individual kidneys remained stable, 17 of 18 kidneys were normal as judged by
      both renography and pyelography, and the occurrence and degree of colonic reflux
      decreased. There was a tendency for the rectal capacity to increase, while the
      total residual tended to decrease solely due to the decrease in colonic residual.
      These results indicate that the ileocecal rectal bladder functions well as an
      internal continent reservoir and that radionuclide investigation is a valuable
      and cost-beneficial means of follow-up of urinary diversions.

PMID- 7627853
TI  - Survival and prognostic factors associated with metastatic nonseminomatous
      testicular and extragonadal germ cell tumors.
AB  - To assess prognostic factors in patients with metastatic nonseminomatous germ
      cell tumors, 50 patients with testicular germ cell tumors (TGCT) and 10 patients
      with extragonadal germ cell tumors (EGGCT) were studied. The clinical staging
      system for testicular tumors proposed by The Japanese Urological Association and
      The Japanese Pathological Society was applied. All patients with EGGCT had
      primary sites in the retroperitoneum. The 3-year survival rates of TGCT and EGGCT
      were 71.9% and 60.0%, respectively, and there were no differences in patient
      characteristics. Patients had significantly worse survival rates if the following
      applied: choriocarcinoma in the primary tumors, serum lactate dehydrogenase level
      greater than twice the upper limit of normal, liver, brain, or mediastinal
      metastases, or retroperitoneal tumors greater than 10 cm. It was concluded that
      the poor-risk group could be defined as those patients having lymph nodal disease
      only (stage II or III A) with retroperitoneal tumors greater than 10 cm, having
      pulmonary disease (stage III B) with retroperitoneal tumors greater than 5 cm, or
      liver, bone or brain metastases (stage III C), and these criteria will predict
      the prognosis for patients with advanced disease because the good-risk patients
      (53% of all patients) and poor-risk patients (47%) in this study had 3-year
      survival rates of 88.7% and 49.7% (p < 0.0001), and complete response rates of
      96.9% and 60.7% (p < 0.005), respectively.

PMID- 7627854
TI  - New indication of testis biopsy for azoospermia: a clinical study in Japanese
      patients.
AB  - Because of the progress made with assisted reproductive techniques, we decided to
      clarify the indication for testis biopsy in Japanese azoospermic patients. A
      total of 88 azoospermic patients were recruited with testis histologies obtained
      by bilateral biopsy. Testicular histology was evaluated using Johnsen's score
      count. Patients with at least 1 testis containing sperm were assigned to the
      active spermatogenesis group. Patients whose testes had no sperm were assigned to
      the hypospermatogenesis group. Differences in terms of the clinical data between
      the 2 groups were analyzed. Clinical data consisted of past history, physical
      examination and hormone concentrations. The unpaired t test was generally used to
      examine the statistical significance of any differences between the 2 groups. 1)
      There were significant differences between the 2 groups in the levels of serum
      testosterone and luteinizing hormone. 2) There were markedly significant
      differences between the 2 groups in terms of testis volume and the concentration
      of serum follicle-stimulating hormone (FSH). 3) The smallest testis volume and
      the highest serum FSH value in the active spermatogenesis group were 7 ml and
      32.7 mlU/ml (normal range 2.9-8.2), respectively. In conclusion, although the
      presence or absence of active spermatogenesis can be accurately predicted by
      measuring the testis volume and serum FSH, testis biopsy should be carried out in
      patients with a testis volume greater than 7 ml or a serum FSH less than 4 times
      normal when the use of assisted reproductive techniques are planned.

PMID- 7627855
TI  - Conservative management of non-traumatic subcapsular renal hematoma: a case
      report.
AB  - The case of a 78-year-old woman with a non-traumatic subcapsular renal hematoma
      is described. She complained of right flank pain and fever and the findings
      following abdominal echography, computerized tomography (CT) scan and renal
      angiography agreed with a diagnosis of subcapsular renal hematoma without renal
      tumor. Percutaneous drainage of the hematoma improved her clinical symptoms and
      the lesion was seen on CT scan. Ten months later, no change in the right kidney
      could be seen on CT scan and echography. We conclude that conservative management
      is the first choice for subcapsular renal hematoma without a definite etiology,
      especially in an elderly patient.

PMID- 7627856
TI  - Primary adenocarcinoma of the vermiform appendix associated with transitional
      cell carcinoma of the bladder.
AB  - A case of primary adenocarcinoma of the vermiform appendix coexisting with
      transitional cell carcinoma (TCC) of the bladder is presented. The patient was a
      74-year-old male who underwent radical cystectomy with continent urinary
      diversion using the Florida pouch. Two different cancers were found, TCC of the
      bladder and mucinous adenocarcinoma of the appendix. To our knowledge, this is
      the only such case reported in the medical literature.

PMID- 7627857
TI  - Synchronous inverted papilloma and submucosal leiomyoma of the urinary bladder.
AB  - We report a case of synchronous inverted papilloma and submucosal leiomyoma of
      the bladder in a 43-year-old man and review the relevant literature.

PMID- 7627858
TI  - A case of testicular teratoma located in the opposite side of the upper abdominal
      wall.
AB  - We report a case of a testicular teratoma located in the opposite side of the
      upper abdominal wall. A 2-year-old boy presented with a non-palpable right testis
      and underwent right inguinal exploration for right cryptorchidism. During
      surgery, the tumor was found in the opposite side of the upper abdominal wall
      across the midline. Histological investigation of the tumor revealed a mature
      teratoma occurring in the intra-abdominal testis. No such case has been
      previously reported.

PMID- 7627859
TI  - Primary diffuse large cell lymphoma of the penis.
AB  - A 66-year-old man presented with malignant lymphoma of the penis. This was of
      considerable interest because the penis is an extremely uncommon site for primary
      lymphoma. This patient had no evidence of nodal disease at presentation and so
      was treated with radiotherapy. He is now cured and both the structure and
      function of his penis have been preserved.

PMID- 7627860
TI  - Mullerian duct cyst with 46, XYq-.
AB  - We report a case of a mullerian duct cyst associated with a 46, XYq- chromosome
      anomaly. Mullerian duct cyst is a consequence of the abnormal regression of
      paramesonephric derivative. In the past many different manifestations have been
      associated with the 46, XYq-, anomaly. We discuss the possibility that a
      mullerian duct cyst may be one clinical manifestation of 46, XYq-.

PMID- 7627861
TI  - The migrating motor complex modulates intestinal motility response and rate of
      gastric emptying of caloric meals.
AB  - The present study elucidates whether the phase of the migrating motor complex
      (MMC) present at the moment of food intake modulates postprandial motor response
      and rate of gastric emptying of caloric meals. Eight healthy male volunteers with
      a mean age of 26 years were examined twice. During water-perfused gastroduodenal
      manometry, a liquid meal with paracetamol added as a marker was orally
      administered during phase I and late phase II. Paracetamol appeared in serum 14.1
      +/- 3.8 min and 9.1 +/- 4.0 (mean +/- SD) min, respectively, after intake of the
      meal (P < 0.02). The area under the curve of s-paracetamol until 25 min after
      intake was 232 +/- 169 mumol l-1 min and 362 +/- 130 (P < 0.05), respectively.
      When taken during late phase II, a phase III-like activity occurred within 2.1 +/
      1.3 min in the duodenum, and was succeeded by quiescence. During phase I, the
      meal invariably initiated irregular contractions within 4 min. The phase of MMC
      during which a caloric meal is ingested modulates duodenal motor response and
      rate of gastric emptying during the initial postprandial period. Initial
      postprandial motor activity thus represents the combined effect of nutrient
      stimulation and the underlying enteric biorhythm as reflected by phase of MMC.

PMID- 7627862
TI  - The effect of hormones and peptides involved in water balance on rat colonic
      motility in vitro.
AB  - We have previously shown that restriction of water intake decreased stool
      frequency and stool weight in volunteers. The aim of this study was to
      investigate whether these effects of thirst could be mediated by an action of
      systematically released hormones on colonic smooth muscle. Using isolated colonic
      smooth muscle strips the effect of arginine-vasopressin (AVP), angiotensin II
      (ANG II) and aldosterone on rat colonic motility in vitro was investigated. AVP
      (10(-12)-10(-10) mol/l) and aldosterone (3 x 10(-10)-3 x 10(-8) mol/l) and
      physiological hormonal concentrations of ANG II (10(-13)-10(-10) mol/l) had no
      effect on either basal activity, direct stimulation of colonic smooth muscle or
      neurally stimulated contractions using carbachol 10(-7)-3 x 10(-5) mol/l or
      neurally stimulated contractions using electrical field stimulation at various
      stimulation frequencies (1-10 pps, 1 ms, 40 V). ANG II in higher concentrations
      (10(-7)-10(-6) mol/l) increased basal activity and neurally mediated
      contractions. Accordingly, ANG II (10(-6) mol/l) caused a prestimulation but did
      not increase the maximum contractile effect of carbachol. The response to ANG II
      was not affected by atropine (10(-6) mol/l). TTX (10(-6) mol/l) and N-nitro-L8
      arginine (L-NNA) (3 x 10(-4) mol/l) stimulated basal muscular activity but did
      not affect the maximum contractile effect of ANG II. Systemic serum
      concentrations of AVP, aldosterone and ANG II are presumably not involved in
      thirst-induced colonic motility changes. The ANG II effect in higher
      concentrations is mediated by a direct stimulatory smooth muscle effect and/or by
      facilitating neuronal liberation of acetylcholine.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7627863
TI  - Ambulatory oesophageal pressure, pH and ECG recording in patients with normal and
      pathological coronary angiography and intermittent chest pain.
AB  - The present study was performed to compare pain-related oesophageal motility,
      gastro-oesophageal reflux and ST-segment deviations in patients with intermittent
      chest pain and normal or pathological coronary angiography. Thirty patients (11
      males, 19 females; mean age 54.8 years) with normal and 15 patients (12 males, 3
      females; mean age 66.7 years) with pathological coronary angiography were
      investigated by 24-h oesophageal pressure, pH and ECG recording. Chest pain
      correlated with motility abnormalities or gastro-oesophageal reflux occurred in
      33% (10/30) of patients with normal coronary arteries and in 26% of patients with
      pathological coronary angiography. Symptomatic and asymptomatic ST-segment
      changes were less frequently observed in patients with normal angiography (4/30)
      than in patients with pathological coronary angiography (7/14; P = 0.02).
      Oesophageal dysfunction coincided with ST-segment deviation in 6.7% (2/30) of
      patients with normal and 40% (6/15) of patients with pathological coronary
      angiography (P = 0.02). The conclusions reached were: (1) pain-correlated
      abnormal motility or gastro-oesophageal reflux occurred in patients with normal
      and pathological coronary angiography at the same frequency; (2) ambulatory
      motility and pH recording alone does not appear to differentiate between cardiac
      and non-cardiac chest pain; (3) simultaneous ECG recording reveals a significant
      correlation of ST-segment deviation and gastro-oesophageal reflux or abnormal
      motility in patients with coronary artery stenosis.

PMID- 7627865
TI  - Effect of electrical stimulation on gastric electrical activity, motility and
      emptying.
AB  - The aim was to measure the effect of gastric electrical stimulation on the
      frequency of canine antral pacesetter potentials (PPs), the strength of antral
      contractions, and the rate of gastric emptying while fasting, after feeding and
      with pentagastrin stimulation. Four conscious dogs with a stimulating electrode
      placed 10 cm proximal to the pylorus and recording electrodes and strain gauges
      placed 7, 5 and 3 cm proximal to the pylorus underwent myoelectric and strain
      gauge recordings while fasting, after feeding (250 ml 5% dextrose labelled with
      polyethylene glycol), and during pentagastrin infusion (0.5 micrograms kg-1 min
      1) on four separate days. On each day, electrical stimulation was done using one
      of four stimulation frequencies (0, 6, 30 and 1200 stimuli per minute [s.p.m.]).
      Stimulation at 6 and 30 s.p.m. increased the fasting and fed PP frequency,
      whereas 1200 s.p.m. stimulation did not. Feeding decreased the maximum driven
      frequency, and pentagastrin increased it. Neither the motility index nor the
      gastric emptying rate were consistently changed by stimulation at any frequency.
      In conclusion, canine proximal antral stimulation at 6 and 30 s.p.m. sped PP
      frequency during fasting and after feeding, but stimulation over a wide range of
      frequencies had little effect on gastric contractions and emptying.

PMID- 7627864
TI  - Inhibition of the migrating motor complex by duodenal drainage in man.
AB  - The effect of varying bile acid output on fasting small intestinal motility was
      investigated in healthy male volunteers. Biliary output was manipulated by
      jejunal infusion of isotonic mannitol, which resulted in increased output, and by
      prolonged drainage of duodenal contents, which resulted in decreased output.
      Intestinal motility was measured by manometric recordings performed at four
      levels in the proximal small intestine. A marker dilution technique was used to
      measure pancreatico-biliary output. There were three experimental groups:
      duodenal drainage, non-drainage and control. Both duodenal drainage and non
      drainage groups underwent jejunal saline infusion, followed by mannitol infusion.
      The control group did not receive drainage or infusions. In the drainage group,
      0.41 (0.13-0.68) activity fronts of the migrating motor complex (MMC) per hour
      were recorded during saline infusion, but only 0.06 (0-0.19) activity fronts per
      hour were observed during mannitol infusion. In the non-drainage group, 0.71
      (0.61-0.81) activity fronts per hour were observed during saline infusion and
      0.50 (0.18-0.82) activity fronts per hour were recorded during mannitol infusion.
      In the control group, 0.58 (0.33-0.84) activity fronts per hour were recorded
      during the first 4-h session and 0.58 (0.45-0.71) activity fronts per hour during
      the second session. There was no difference between the number of activity fronts
      per hour observed in the control group and those observed in the saline infusion
      of the drainage group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7627866
TI  - Gastric but not duodenal motor effects of oral erythromycin are dose related.
AB  - There has been increasing interest in the potential use of erythromycin as a
      prokinetic agent, despite limited data on the effect of oral administration on
      gastrointestinal motility. We have now evaluated, in 15 conscious pigs fitted
      with strain gauges, the response of (i) basal gastric motility and (ii) gastric
      motility during inhibition with intraduodenal triglycerides infusion to
      increasing doses of oral erythromycin. In the basal state, erythromycin led to
      dose-dependent increases in both the amplitude (10-30 mg kg-1) and the frequency
      (10-55 mg kg-1) of gastric contractions. The corpus was more responsive than the
      antrum, with an increase in amplitude at lower doses. The amplitude of the
      duodenal contractions was also improved but not in a dose-dependent manner.
      Gastroduodenal coordination was unchanged regardless of the dose of erythromycin.
      Following inhibition of gastric motility, a dose of erythromycin below 45 mg kg-1
      increased both the amplitude of gastric contractions and the gastroduodenal
      coordination, although individual doses produced smaller increases in amplitude
      than in the basal state. These results suggest that erythromycin has a different
      mechanism of action in the stomach compared with the duodenum. The reduced
      effectiveness of large doses of erythromycin has important therapeutic
      implications.

PMID- 7627867
TI  - Autonomic dysfunction in patients with achalasia.
AB  - It has been previously shown that patients with achalasia may have motor
      abnormalities of the stomach, small bowel and biliary system. This study
      investigates whether a disturbance of extraintestinal autonomic function occurs.
      Autonomic function studies were performed in 15 patients with achalasia and 15
      age- and sex-matched healthy controls. Pupillograms were obtained during
      darkness, light exposure and after pilocarpine administration. Cardiovascular
      function studies included determinations of heart rate variation during deep
      breathing and orthostasis. In addition, we determined blood pressure changes in
      response to sustained handgrip, cold exposure and orthostasis. Neurohormonal
      function was investigated by measuring serum pancreatic polypeptide (PP) levels
      prior to and following sham feeding. Pupillary function did not differ in
      patients as compared with controls. However, 9 of 15 patients (95% CI: 32-84%)
      and none of the controls showed at least one abnormal autonomic cardiovascular
      response. A significant difference between the two groups was observed in
      sympathetic function (P = 0.023). More patients than controls did not respond to
      sham feeding with a PP increase. It is concluded that some patients with
      achalasia exhibit an abnormality of the autonomic nervous system that extends
      beyond the gastrointestinal tract. These abnormalities mainly concern
      cardiovascular function but may also involve neurohormonal responses.

PMID- 7627868
TI  - Inhibition of gastric motility induced by intestinal glucose in awake rats: role
      of Na(+)-glucose co-transporter.
AB  - Carbohydrates are a component of chyme that initiate feedback control of gastric
      emptying. The aim of the study was to investigate the mechanism by which sensors
      in the intestine are activated by carbohydrate to initiate intestinal feedback of
      gastric motor function. Intestinal perfusion with D-glucose inhibited gastric
      motility in awake rats. This response was reproduced by 3-O-methyl glucose, a non
      metabolizable analogue of glucose that is absorbed by the Na(+)-glucose co
      transporter, but not by 2-deoxy-D-glucose, and was attenuated by perfusion of the
      intestine with phloridzin, a competitive blocker of the Na(+)-glucose co
      transporter. Feeding a high carbohydrate diet to increase the number of co
      transporters reduced the response to intestinal glucose. It was concluded that
      activation of sensors to initiate feedback inhibition of gastric motility may be
      dependent either on rapid accumulation of glucose within epithelial cells or on
      activation of the Na(+)-glucose co-transporter.

PMID- 7627869
TI  - What are the primary nursing diagnoses to be considered when planning care for
      the patient with Ramsay Hunt syndrome?

PMID- 7627870
TI  - Leech therapy for venous congestion following myocutaneous pectoralis flap
      reconstruction.
AB  - Medicinal leech therapy is recorded as early as 200 B.C. to treat everything from
      mental illness to headaches. The medicinal leech (Hirudo medicinalis) is used
      today as a successful treatment for venous congestion following replantation or
      transplantation of tissue. This paper discusses specific leeching properties,
      indications for use, nursing care and expected outcomes of leech therapy.

PMID- 7627872
TI  - Nursing care of the patient with trismus.
AB  - This paper discusses trismus (mandibular hypomobility), addressing its
      etiologies, relevant anatomy and pathophysiology, with the medical and nursing
      care of trismic patients commonly seen in the otolaryngology setting. It aims to
      raise awareness among ORL nurses about the sometimes subtle presentation of
      trismus and about the important role ORL specialists can play in detecting and
      treating this debilitating disorder.

PMID- 7627871
TI  - Acoustic neuroma standard of care.
AB  - Patients who have undergone acoustic neuroma surgery require expert,
      comprehensive nursing care. This article includes a standard of care and tables
      about neurological assessment, potential complications, home safety and discharge
      instructions. A holistic, multidisciplinary approach can enable nurses to promote
      the recovery of acoustic neuroma patients and ultimately improve their outcomes.

PMID- 7627873
TI  - Presidential address: "the challenges are yours".

PMID- 7627874
TI  - Meniere's disease: a review of the problem.
AB  - Meniere's Disease can be an incapacitating problem for patients. This article
      discusses the history of Meniere's Disease, symptomatology, diagnostic testing,
      treatment modalities, and nursing diagnoses associated with the problem.

PMID- 7627875
TI  - Aspiration: causes, consequences, and prevention.

PMID- 7627876
TI  - Practice guidelines: epiglottitis.

PMID- 7627877
TI  - Practice guidelines: chronic otitis media/chronic mastoiditis/cholesteatoma.

PMID- 7627878
TI  - Practice guidelines: body image disturbance.

PMID- 7627879
TI  - Restructuring, redesigning, and redirecting our future.

PMID- 7627880
TI  - Politically correct ... a nursing responsibility enhanced by the Nurse in
      Washington Internship.
AB  - Understanding the legislative process is the right of every citizen. Being
      concerned, knowledgeable, and committed to political activity is the
      responsibility of each citizen. Over two million American citizens are registered
      nurses. Nursing's responsibility is to prepare nurses to be politically
      knowledgeable, correct and active in the establishment of health care policy
      which affects the nation's citizens. One opportunity to achieve this in nursing
      practice is to use the knowledge shared at the Nurse in Washington Internship
      (NIWI).

PMID- 7627881
TI  - The challenges of change.

PMID- 7627882
TI  - Insurance claims: how to make the process as smooth as possible.

PMID- 7627883
TI  - Redefining success in dentistry.

PMID- 7627884
TI  - Canada's Laboratory Centre for Disease Control.

PMID- 7627885
TI  - Prescription drug approval in Canada: a risk-benefit analysis.

PMID- 7627887
TI  - Fifty years of fluoridation.

PMID- 7627886
TI  - Dental devices: the dangers of cross-border shopping.

PMID- 7627888
TI  - Toward a caries-free society--fluoride therapies for today and the next century.

PMID- 7627889
TI  - Diagnosis and management of vertical root fractures.
AB  - Vertical root fractures constitute a significant management problem for dentists.
      The diagnosis of root fractures is difficult because several of their signs and
      symptoms are shared with other common dental or oral pathologies. However,
      reaching an accurate diagnosis is crucial to establishing the prognosis for a
      fractured tooth and selecting the appropriate treatment. This review describes
      current knowledge of the causes, diagnosis, and management of vertical root
      fractures, with special attention to the periodontal aspects of this condition.

PMID- 7627890
TI  - Removable partial denture design by Canadian dental laboratories: a retrospective
      study.
AB  - Identical, unilateral, distal extension base (DEB) maxillary and mandibular casts
      with a posterior modification area were mailed to 15 Canadian commercial dental
      laboratories. Each cast was accompanied by a letter explaining the purpose of the
      study and a request for the laboratory to design a RPD-U and RPD-L framework. The
      package also included a questionnaire on the techniques commonly used by dentists
      in the construction of a removable partial denture prosthesis, as well as the
      laboratory procedures they requested from laboratory technicians. Compared to the
      findings of previous studies by McCracken and others, the results of this study
      indicate an improvement in the dentists' understanding of the fundamental
      principles of an RPD framework design. However, the questionnaire also revealed
      the need for improved communication between the dentist and the technician. The
      study suggests that the basic principles for the construction and design of
      removable partial dentures, as taught in dental schools across Canada, must be
      respected by dentists.

PMID- 7627891
TI  - [Herpesvirus infection: from the primary oral lesion to recurrent herpes].
AB  - This paper presents an overview of the clinical conditions associated with a
      herpetic lesion at the time of the primary infection, as a true primary infection
      or a first herpetic accident, or during recurrences. The virus responsible, its
      anatomy and its functioning are detailed. The etiology and transmission of
      herpetic viral infection, its evolution and complications, as well as diagnostic
      aids are also discussed. To complete the discussion of this chronic disease which
      can cause acute annoyances treatment, particularly for children is reviewed, and
      suggestions are made to prevent it.

PMID- 7627892
TI  - Medical pollution?

PMID- 7627893
TI  - Prevention of pterygium recurrence: conjunctival grafts vs. mitomycin C.

PMID- 7627894
TI  - Prevention of pterygium recurrence: conjunctival grafts vs. mitomycin C.

PMID- 7627895
TI  - Prostacyclin-thromboxane balance and retinal vascular pattern in rats with
      experimentally induced diabetes.
AB  - OBJECTIVE: To search for relationships between alterations in vascular and
      platelet function and the retinal vascular pattern in male Wistar rats with
      streptozocin-induced diabetes after various periods of evolution of the disease.
      NUMBERS: Five groups of five diabetic rats were studied, the duration of diabetes
      being 15 days or 2, 3, 6 or 9 months; a control group comprised six nondiabetic
      rats. Each diabetic rat that died was replaced with a new animal, for a total of
      46 animals. All deaths occurred within the first 5 days of induction of the
      disease. MAIN OUTCOME MEASURES: Blood glucose level, intensity of platelet
      aggregation, thromboxane B2 level, aortic 6-keto-prostaglandin F1 alpha level,
      retinal vascular morphology, percentage of retinal area covered by vessels
      stained with horseradish peroxidase (HRP) in photomicrographs. RESULTS:
      Thromboxane B2 production increased with the duration of diabetes (r = 0.91, p <
      0.001), and aortic 6-keto-PGF1 alpha production decreased in relation to blood
      glucose concentration (r = -0.95, p < 0.003). Alterations in retinal vascular
      pattern were related to both blood glucose and vascular prostacyclin
      concentrations. The retinal area covered by HRP-stained vessels was 79.3% lower
      in the diabetic rats than in the nondiabetic rats, and this inhibition was
      maintained throughout the experimental period. CONCLUSIONS: We postulate that a
      decrease in prostacyclin production in association with high glucose levels plays
      an important role in the development of retinal vascular alterations in
      streptozocin-diabetic rats, although an influence of thromboxane cannot be ruled
      out.

PMID- 7627896
TI  - Invasive rhinosino-orbital aspergillosis with precipitous visual loss.
AB  - OBJECTIVE: To describe the clinicopathological and radiologic features in five
      cases of primary and secondary orbital aspergillosis. DESIGN: Case series.
      SETTING: Ophthalmology department of a university hospital. PATIENTS: Five
      patients over 65 years of age with invasive rhinosino-orbital aspergillosis.
      RESULTS: Presenting features were abrupt onset of proptosis, ophthalmoplegia and
      blepharoptosis with precipitous visual loss. All had debilitating periorbital
      pain or headache, but none had orbital inflammatory signs or appeared "toxic."
      Predisposing causes included alcoholism, low-dose prednisone therapy and insulin
      dependent diabetes mellitus. One patient, suspected of having mucormycosis based
      on tissue biopsy and results of potassium hydroxide preparations, harboured
      Aspergillus fumigatus, which grew on culture. Secondary bacterial infections
      developed in three patients. Three patients died from their disease despite
      aggressive surgical treatment, including exenteration and sinus extirpation. The
      one patient with primary orbital aspergillosis survived after exenteration.
      CONCLUSIONS: Sinonasal aspergillosis with orbital extension and primary orbital
      aspergillosis have a precipitous clinical course that mimics that of mucormycosis
      and may be fatal despite early exenteration. Computed tomography and magnetic
      resonance imaging of the sinuses, orbit and head provide complementary diagnostic
      signs. While results of potassium hydroxide preparations and tissue biopsy guide
      treatment of fungal infection, definitive diagnosis requires fungal culture.
      Relatively good vision may be associated with massive orbital and secondary
      intracranial extension.

PMID- 7627897
TI  - Autosomal dominant keratitis: a possible aniridia variant.
AB  - OBJECTIVE: To describe the findings in a family with hereditary keratitis.
      DESIGN: Case series. SETTING: Eye genetics clinic at a university-affiliated
      hospital in Edmonton. PATIENTS: Fifteen affected members, nine female and six
      male, of a four-generation family with hereditary keratitis. RESULTS: The pattern
      of transmission was consistent with autosomal dominant inheritance. The disorder
      was characterized by the presence of a circumferential band of opacification and
      vascularization at the level of Bowman's membrane adjacent to the limbus.
      Progression toward the central cornea occurred in some instances. Penetrating
      keratoplasty was performed in certain cases when the visual axis was involved and
      the acuity deteriorated. Histopathological studies confirmed the inflammatory
      nature and the anterior stromal localization of the keratitis. Thirteen of the
      affected members in whom a detailed fundus examination was possible had macular
      hypoplasia. Several had abnormalities of the iris, including iris stromal defects
      and ectropion uveae. CONCLUSIONS: The presence of macular hypoplasia in
      association with the iris and corneal changes suggests that autosomal dominant
      keratitis is likely a variant of aniridia.

PMID- 7627898
TI  - Familial variation in retinal pigmentation in adenomatous polyposis.
AB  - OBJECTIVE: To examine the relationship between familial adenomatous polyposis and
      retinal pigment epithelial (RPE) pigmentation in affected patients and their
      first-degree relatives. DESIGN: Retrospective study. SETTING: Affected families
      across Canada registered in the Steve Atanas Stavro Familial Gastrointestinal
      Cancer Registry. SUBJECTS: A total of 134 subjects aged 10 to 35 years (at high
      risk for the disease) who had undergone examination of the gut by sigmoidoscopy,
      colonoscopy with biopsy or resection with biopsy and indirect ophthalmoscopy.
      MAIN OUTCOME MEASURES: Weighted eye score for large and small retinal lesions;
      family eye pigmentation index (FEPI), calculated from the weighted eye scores for
      individual affected family members. RESULTS: Families differed in the number and
      type of RPE lesions manifest, but affected family members showed similar
      pigmentation. An FEPI below 3 was uninformative, but with a medium or high FEPI
      the sensitivity and specificity of the index approached 100%. CONCLUSIONS: A
      positive retinal examination signifies a high risk for adenomatous polyposis,
      whereas a negative retinal examination is uninformative. Current molecular
      analysis is informative in 95% of families. However, in cases of spontaneous
      mutation and in patients with no first-degree relatives available or with unknown
      parenthood, RPE lesions are the most valuable extracolonic manifestation of
      adenomatous polyposis.

PMID- 7627899
TI  - Corneal epithelial fragility in diabetes mellitus.
AB  - OBJECTIVE: To assess corneal epithelial fragility in non-insulin-dependent
      diabetes mellitus (NIDDM) and its association with retinopathy. DESIGN: Survey.
      SETTING: University-affiliated hospital in Chandigarh, India. SUBJECTS: Seventy
      patients with NIDDM selected at random and 35 age-matched healthy control
      subjects recruited from hospital staff and their relatives. MAIN OUTCOME MEASURE:
      Corneal epithelial fragility, as measured with an esthesiometer. RESULTS: Mean
      corneal epithelial fragility values were significantly higher for the diabetic
      subjects without retinopathy than for the control subjects (p < 0.05). The mean
      epithelial fragility values for the eyes with diabetic proliferative retinopathy
      and those with nonproliferative retinopathy were significantly higher (by 84% and
      41% respectively) than the mean value for the diabetic subjects without
      retinopathy (p < 0.05). There was no significant difference in mean epithelial
      fragility values between the proliferative and nonproliferative retinopathy
      groups. CONCLUSIONS: Eyes with diabetic retinopathy demonstrate increased corneal
      epithelial fragility.

PMID- 7627900
TI  - Can ptosis incidence be reduced after lid injections of botulinum A exotoxin for
      blepharospasm and hemifacial spasm?

PMID- 7627901
TI  - Outpatient postvitrectomy fluid-gas exchange using long-acting gasses.

PMID- 7627902
TI  - Fatal case of group B streptococcal endogenous endophthalmitis.

PMID- 7627903
TI  - Granular cell tumour of the orbit.

PMID- 7627905
TI  - Interpreting technology. Power failure.

PMID- 7627904
TI  - Aicardi's syndrome. A clinicopathological report.

PMID- 7627906
TI  - Survival of and lacZ expression in recombinant Pseudomonas strains introduced
      into river water microcosms.
AB  - The lacZY gene cassette inserted into the chromosome of Pseudomonas aeruginosa
      UG2Lr and Pseudomonas aureofaciens Ps3732RNL11 was used as a genetic marker to
      study the fate of the Pseudomonas strains in river water microcosms. Expression
      of the lacZ marker in UG2Lr and Ps3732RNL11 was detected in microcosms containing
      as few as 12 and 14 colony-forming units (cfu)/mL of river water, respectively,
      by fluorimetric measurement of the beta-galactosidase activity against 4
      methylumbelliferyl-beta-D-galactoside as the substrate. The persistence of and
      lacZ expression in the pseudomonas strains were monitored in sterile and
      nonsterile river water in the presence and absence of added nutrients by dilution
      plating and fluorimetry, respectively. After incubation for 10 d at 10 degrees C,
      culturable populations of strain UG2Lr in sterile water samples, with and without
      nutrient added, decreased from an initial density of 1.5 x 10(4) to 1.7 x 10(3)
      and 4.6 x 10(3) cfu/mL, respectively. Despite similar numbers of UG2Lr cells in
      the two treatments, expression of the lacZ marker in the surviving cells of the
      nutrient-supplemented sample was 24 times higher than in the cells of the
      unamended sample. In nonsterile water samples, the density of UG2Lr declined to
      less than 6 cfu/mL in 30 d regardless of the nutrient conditions. A nutrient
      supplement increased the growth of the native bacterial population but did not
      enhance growth of and lacZ expression in the bacteria. Polymerase chain reaction
      analysis showed a decrease in amplification signal indicating a genuine decline
      in viable UG2Lr cell density in the water samples.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7627907
TI  - Degradation of polycyclic aromatic hydrocarbons (PAHs) by a mixed culture and its
      component pure cultures, obtained from PAH-contaminated soil.
AB  - A mixed culture, isolated from soil contaminated with polycyclic aromatic
      hydrocarbons (PAHs), grew on and degraded fluoranthene in aqueous media
      supplemented with glucose, yeast extract, and peptone. Increased complex nitrogen
      levels in the medium promoted bacterial growth and a greater extent of
      fluoranthene degradation. Amendment of the media with high glucose levels also
      diminished specific fluoranthene degradation. The mixed culture was capable of
      degrading a range of other PAHs, including benzo[a]pyrene, anthracene,
      phenanthrene, acenaphthene, and fluorene. The mixed culture contained four
      predominant isolates, all of which were Gram-negative rods, three of which were
      identified as Pseudomonas putida, Flavobacterium sp., and Pseudomonas aeruginosa.
      Better degradation of a defined PAH mixture was observed with the mixed culture
      than with individual isolates. A reconstituted culture, prepared by combining the
      four individual isolates, manifested a similar PAH biodegradation performance to
      the original mixed culture. When compared with the mixed culture, individual
      isolates exhibited a relatively good capacity to remove more water-soluble PAHs
      (acenaphthene, fluorene, phenanthrene, fluoranthene). In contrast, removal of
      less water-soluble PAHs (anthracene and pyrene) was low or negligible with
      isolated cultures compared with the mixed culture.

PMID- 7627908
TI  - The oxidation of pyrene and benzo[a]pyrene by nonbasidiomycete soil fungi.
AB  - The purpose of this study was to determine the ability of nonbasidiomycete soil
      fungi to oxidize pyrene (four rings) and benzo[a]pyrene (BaP) (five rings). Fungi
      were isolated from five different soils in which the polycyclic aromatic
      hydrocarbon content ranged from 0.8 to 80 micrograms/g dry soil. Approximately
      50% of the isolates in all sites were able to oxidize pyrene. The pyrene
      oxidizing species belonged to all fungal divisions except basidiomycetes. The
      most common were Penicillium spp. of the subgenus Furcatum and these dominated
      the more contaminated soils. Penicillium janthinellum and Syncephalastrum
      racemosum exhibited the most rapid rates of pyrene oxidation. The major pyrene
      metabolites were identified by proton NMR and mass spectrometry as 1-pyrenol, 1,6
      and 1,8-pyrenediol, and the 1,6-and 1,8-pyrenequinones. A high correlation was
      found between the ability to oxidize pyrene and BaP. As with pyrene,
      approximately 50% of the fungal isolates tested oxidized BaP to 9-hydroxy-BaP.
      Eighty percent of the pyrene-oxidizing strains were also able to metabolize BaP.

PMID- 7627909
TI  - Dynamics of non-O1 Vibrio cholerae and fecal coliforms in experimental
      stabilization ponds in the arid region of Marrakesh, Morocco, and the effect of
      pH, temperature, and sunlight on their experimental survival.
AB  - We studied the spatial-temporal dynamics of non-O1 Vibrio cholerae numbers at a
      stabilization pond treatment plant. This bacterium's seasonal dynamics were the
      inverse of those of fecal coliforms, with high levels in hot periods and low
      levels in cold periods. Stabilization pond treatment did not significantly reduce
      non-O1 V. cholerae numbers between the system's inflow and outflow points. In
      contrast, fecal coliforms were reduced by 98.95% in hot periods and by 94.91% in
      cold periods. Significant rho coefficient values for the Spearman correlation
      between numbers of non-O1 V. cholerae and temperature and pH of 0.91 and 0.76
      respectively, were found at the system's outflow point. An experimental study of
      the effects of pH, temperature, and sunlight on the survival of non-O1 V.
      cholerae and fecal coliforms confirmed the inverse behaviour of the two bacterial
      groups noted in the stabilization ponds. Alkaline pH values of 8 and 8.8 promoted
      the survival of non-O1 V. cholerae and inhibited that of Escherichia coli. Low
      temperatures (8 degrees C) prolonged E. coli survival (k = 0.002/h), while a
      temperature of 23 degrees C reduced it markedly (k = 0.022/h). Non-O1 V. cholerae
      did not survive as well as E. coli at 8 degrees C (k = 0.009/h). The effect of
      temperature on non-O1 V. cholerae appeared to be closely linked to nutrient
      levels. Non-O1 V. cholerae appeared to be less sensitive to sunlight than E. coli
      whose survival was markedly reduced particularly during summer periods. Non-O1 V.
      cholerae and E. coli did not behave in the same way in water subjected to
      stabilization pond treatment. The use of fecal coliforms as an indicator of the
      potential health hazard of the effluent may not be adequate for this treatment
      procedure.

PMID- 7627910
TI  - "Hysteria" in clinical neurology.
AB  - Hysteria is an ancient word for a common clinical condition. Although it no
      longer appears in official diagnostic classifications, "hysteria" is used here as
      a generic term to cover both "somatoform" and "dissociative" disorders as these
      are related psychopathological states. This paper reviews the clinical features
      of four hysterical syndromes known to occur in a neurologist's practice, viz
      conversion, somatization and pain disorders, and psychogenic amnesia. The
      presence in the clinical history of a multiplicity of symptoms, prodromal stress,
      a "model" for the symptom(s), and secondary reinforcement all suggest the
      diagnosis, and minimise the need for extensive investigations to rule out organic
      disease. Psychodynamic, behavioral, psychophysiologic and genetic factors have
      been proffered to explain etiology. Appropriate treatment involves
      psychotherapeutic, behavioral and pharmacological techniques. A basic requirement
      is to avoid errors of commission such as multiple specialist referrals and
      invasive diagnostic and treatment procedures. Hysteria is a remediable condition
      if identified early and managed appropriately.

PMID- 7627911
TI  - O6-methylguanine-DNA methyltransferase in tumors and cells of the oligodendrocyte
      lineage.
AB  - BACKGROUND: Oligodendrogliomas respond to nitrosourea-based chemotherapy and are
      induced in rats following transplacental exposure to ethylnitrosourea,
      observations suggesting that neoplastic and normal cells of the oligodendrocyte
      lineage are "sensitive" to nitrosoureas. Nitrosoureas alkylate DNA at O6-guanine
      with repair mediated by O6-methylguanine-DNA methyltransferase (MGMT). The
      cytotoxic and carcinogenic properties of the nitrosoureas appear related to MGMT
      activity. METHODS: To explore why oligodendrogliomas respond to chemotherapy, we
      measured MGMT activity in five chemosensitive human oligodendrogliomas and in rat
      oligodendrocyte lineage cells. We also measured MGMT activity in rat astrocytes
      and compared the cytotoxic effects of carmustine (BCNU) on oligodendrocyte
      lineage cells and astrocytes. RESULTS: Low levels of MGMT activity were found in
      five of five human oligodendrogliomas. Cultures of neonatal rat glia enriched for
      oligodendrocyte lineage cells also had low levels of MGMT activity, approximately
      one-third that found in astrocytes (p < 0.02), and oligodendrocyte lineage cells
      were more sensitive to BCNU than astrocytes. CONCLUSIONS: Low MGMT activity may
      contribute to the chemosensitivity of some human oligodendrogliomas and rat
      oligodendrocyte lineage cells also have low levels. If drug resistance mechanisms
      in tumors reflect the biochemical properties of their cells of origin, then
      normal glia may serve as a laboratory substitute for human glioma.

PMID- 7627912
TI  - Cholinergic mechanisms in generalized seizures: importance of the zona incerta.
AB  - OBJECTIVE: Stimulation of the central cholinergic system results in generalized
      epileptic seizures. The goal of this study was to map the epileptogenic effects
      of the cholinergic agonist, carbachol injected into different sites of the basal
      forebrain and diencephalon of the rat brain. METHODS: Carbachol was injected
      directly into the brain in a dose of 1 or 3 micrograms. Seizures were assessed
      behaviourally on a five-stage scale with electroencephalographic controls.
      Seizures at stage 1 were the least severe and those at stage 5 the most severe.
      RESULTS: Injections of high dose carbachol (3 micrograms) induced seizures from
      40% of all injected brain sites. Injections of low dose carbachol (1 microgram)
      or isotonic saline into the same brain sites did not cause any behavioural or
      electrographic seizures. The majority of sites (84%) producing generalized
      seizures (stage 5) were concentrated in or around the zona incerta. CONCLUSIONS:
      Within the anatomical limits of the study, the zona incerta is the area most
      sensitive to carbachol-induced generalized seizures.

PMID- 7627913
TI  - Risk of intracranial aneurysms in families with subarachnoid hemorrhage.
AB  - BACKGROUND: Genetic factors may be important in the etiology of subarachnoid
      hemorrhage (SAH) and intracranial aneurysm (IA) formation. Several studies have
      reported the familial occurrence of SAH and IA, although in most cases
      asymptomatic family members were not studied with elective angiography. The
      examination of data from large sibships could provide important information about
      the frequency of IA occurrence in at-risk individuals and the mode of inheritance
      for familial SAH/IA. METHODS: We reviewed published case series of sibships with
      SAH and at least four siblings, in which at least one sibling underwent elective
      angiography. Data were collected on age-of-onset, clinical events, presence of
      hypertension, angiographic findings, and outcome. Patients were classified as
      "affected" if they had a SAH or if an IA was detected by elective angiography,
      and "unaffected" if they were asymptomatic and had a negative angiogram. RESULTS:
      Seven case series with 52 individuals (26 men and 26 women) met our inclusion
      criteria. The sibships ranged from 6 to 13 members. Most of the siblings (32 of
      52, 61%) were asymptomatic, 18 (35%) had a SAH, and 2 (4%) had focal symptoms but
      no SAH. Elective angiography of 34 siblings showed an IA in 11 (32%) and was
      negative in 23 (68%). The overall rate of affecteds (SAH or IA) was 56%.
      CONCLUSIONS: Based on data from these sibships, angiography of asymptomatic at
      risk siblings demonstrated an IA in almost one-third of cases. Familial SAH/IA
      segregated with a pattern that was consistent with an autosomal dominant trait in
      this selected series of sibships, although other factors could produce these
      findings.

PMID- 7627914
TI  - Preparatory postural adjustments in parkinsonian patients with postural
      instability.
AB  - BACKGROUND: Postural instability is a common problem in patients with Parkinson's
      disease. This paper reports results of a study undertaken to investigate some of
      the possible mechanisms responsible for this instability. METHODS: Preparatory
      postural adjustments associated with a lateral leg raising task were studied in
      five parkinsonian patients and four age-matched controls. Recordings included
      ground reaction forces, kinematics, and surface EMG activity from multiple leg
      muscles. RESULTS: In normal subjects there was a well-defined sequence of events
      preceding the onset of leg elevation, beginning with a transfer of centre of foot
      pressure (CP), initially toward the moving leg and then back to the support side,
      followed by displacement of the trunk toward the support side. In the more
      severely affected parkinsonian patients, the amplitude of the initial
      displacement of CP was markedly reduced. The interval between the earliest force
      changes and the onset of leg elevation was prolonged and the relative timing of
      the kenematic adjustments during this interval was disrupted. In addition the
      alternating burst and periods of inhibition observed in the EMG recordings from
      the normal subjects were replaced by continuous tonic EMG activity. CONCLUSIONS:
      These observations suggest that abnormalities in programming preparatory postural
      adjustments may contribute to postural instability in some patients with advanced
      Parkinson's disease.

PMID- 7627915
TI  - Psychogenic dystonia: a review of 18 cases.
AB  - OBJECTIVE: To review the clinical characteristics and associated features found
      in patients with psychogenic dystonia. METHODS: A 10 year retrospective chart
      review of all patients diagnosed by the author as having psychogenic dystonia.
      RESULTS: Eighteen patients fulfilled diagnostic criteria for "Documented" or
      "Clinically Established" psychogenic dystonia. Clinical characteristics of the
      dystonia were inconsistent or incongruous with established forms of organic
      dystonia. Fourteen of the 18 patients had a known precipitant. In most, the onset
      was abrupt and progression occurred rapidly, often to fixed dystonic postures. In
      contrast to idiopathic dystonia, involvement of the legs was common (12
      patients), despite onset in adult life. Although cases of isolated paroxysmal
      dystonia were excluded in the review, 10 patients had paroxysmal worsening of
      dystonia or other abnormal movements. Pain was a prominent feature in 14 of 16
      patients with the complaint and 1 patient with documented psychogenic dystonia
      also had well established reflex sympathetic dystrophy (RSD). Other psychogenic
      movement disorders, psychogenic neurological signs and multiple somatizations
      were common. Long-term follow up was available for less than one-half of the
      patients. Outcome varied considerably; some patients had complete resolution of
      symptoms (including 1 who had undergone 2 previous thalamotomies) and others
      remained disabled by persistent dystonia. CONCLUSIONS: Dystonia is uncommonly due
      to primary psychological factors. At times this is an extremely difficult
      diagnosis to make and even when the diagnosis is confirmed, management remains
      very challenging. Future studies are required in hopes of providing more
      efficient means of distinguishing psychogenic dystonia from other dystonic
      syndromes especially those which rarely follow peripheral injury or accompany
      RSD/causalgia syndromes.

PMID- 7627916
TI  - Myoclonic-like finger microdisplacements in patients with cerebellar deficits.
AB  - BACKGROUND: Here we assess the ability of patients with cerebellar disease to
      execute a simple visually-guided movement task involving tracking of a target
      with the index finger. METHODS: Spontaneous microdisplacements in index finger
      position are compared in patients with cerebellar deficits (ischemia [n = 3],
      multiple sclerosis [n = 3], degenerative cerebellar disease [n = 3]) and age
      matched healthy subjects. Subjects were required to maintain a constant finger
      position relative to a stationary baseline displayed on an oscilloscope. RESULTS:
      Unusual transient abrupt movements (saccadic or myoclonic-like) directed with or
      against gravity were seen in patients whose neurological deficits were the most
      severe (7/9 patients). These abrupt myoclonic-like movements occurred
      independently of visual input, were not associated with clinically observable
      myoclonus, and were not detected previously in patients with Parkinson's disease.
      These abrupt myoclonic-like movements were not associated with abnormalities in
      either physiological tremor, or oscillations in finger microdisplacements induced
      by insertion of a delay (300-1400 ms) into the visual feedback of this finger
      "holding" experiment. An unexpected finding is that the results obtained for
      patients with cerebellar deficits by insertion of an experimental delay are not
      significantly different from those obtained with their age-matched controls.
      CONCLUSIONS: These observations suggest that abrupt myoclonic-like movements are
      a characteristic abnormality of patients with a variety of cerebellar deficits
      and emphasize the value of this simple motor tracking task for characterizing
      movement disorders.

PMID- 7627917
TI  - Long term treatment of intractable reflex sympathetic dystrophy with intrathecal
      morphine.
AB  - BACKGROUND: Some patients with reflex sympathetic dystrophy (RD) develop
      intractable symptoms unresponsive to conventional therapy. Recently, intrathecal
      morphine therapy has been used with some success in such patients. METHODS: The
      clinical course of two patients with intractable reflex sympathetic dystrophy
      (RSD) is described. Both patients developed intractable leg pain, swelling and
      autonomic changes after a leg injury. Numerous medical treatments and surgical
      sympathectomies failed to provide long term relief. RESULTS: Relatively
      satisfactory symptom control was achieved only with the use of long term
      intrathecal morphine therapy delivered by subcutaneously implanted infusion
      pumps. Exacerbations of the RSD continued to occur, at times in association with
      further leg trauma, but these could be controlled by a temporary escalation of
      the intrathecal morphine dose. Complications of morphine therapy were relatively
      minor. A red rash appearing over the pump site was the first sign that a drug
      catheter break had occurred, necessitating surgical catheter revision.
      CONCLUSION: Long term intrathecal morphine therapy is a useful treatment option
      for patients with intractable severe RSD who have failed other therapies and
      remain markedly disabled.

PMID- 7627918
TI  - Beta-endorphin in multiple trauma victims.
AB  - BACKGROUND: In animals and in humans, stress is known to be accompanied by
      increased beta-endorphin secretion. METHODS: Blood samples from 47 patients in a
      state of stress induced by multiple trauma were assessed for beta-endorphin
      concentration by radioimmunoassays. RESULTS: We show that there is a clearcut
      correlation (Spearman's R = 0.72, P = 2.1 x 10(-6) between the level of
      consciousness evaluated with the Glasgow score and levels of circulating beta
      endorphin. In addition, beta-endorphin levels are higher than normal in patients
      with Glasgow coma with scores higher than seven, and lower than normal in those
      with Glasgow coma scores of seven or less. Finally, in the complete absence of
      stress (shown by the lack of brain activity in six irreversible coma patients),
      there is a severe drop in the level of circulating beta-endorphin. CONCLUSION:
      beta-endorphin serum levels correlate with the state of consciousness of multiple
      trauma patients.

PMID- 7627919
TI  - [Intraligamentary amyloid deposits in spinal canal stenosis].
AB  - OBJECTIVE: We have searched for amyloid substance in 41 consecutive samples of
      tissue taken during laminectomies performed to relieve spinal canal stenoses. We
      also evaluated the relation between the occurrence of deposits and the age of
      patients. METHODS: Tissue sections were stained with Congo red; positive areas
      had to show green dichroism under polarized light. RESULTS: Small amyloid
      deposits were found in fibrous and fibro-elastic (ligamentum flavum) tissues in
      14 subjects (34%). After age 60, the frequency was close to 50%. It reached 58%
      in those aged 70 or over. Our 3 patients aged 80 or more all had deposits. There
      was also a relation between age and importance of the infiltration. Both sexes
      appeared evenly involved. Systemic amyloidosis (multiple myeloma) was
      demonstrated in a single patient. In this case infiltration was slightly more
      abundant and exceeded ligamentary structures, also involving vascular walls.
      CONCLUSIONS: Small amyloid deposits were frequent in our material. Their presence
      and their abundance were closely related to the age of patients. Rarely, a more
      important infiltration, exceeding ligamentary structures will perhaps suggest a
      systemic form of amyloidosis. A few other rare amyloid conditions (amyloidosis
      associated with prolonged dialysis, amyloid tumour) have been reported to induce
      spinal canal stenosis. The occurrence of amyloid in vertebral ligaments of non
      stenosed elderly persons is not documented; it may represent a new localization
      of senile amyloidosis.

PMID- 7627920
TI  - Delayed myelopathy after trivial neck injury in a patient with a cervical
      neurenteric cyst.
AB  - BACKGROUND: Neurenteric cysts are rare spinal lesions of congenital origin. They
      usually present insidiously with a long history of local spinal pain,
      radiculopathy and myelopathy. We report a 14-year-old male with a high cervical
      neurenteric cyst who developed a progressive myelopathy after minor neck trauma.
      Full recovery followed a partial cyst excision and decompressive procedure.
      SIGNIFICANCE AND CONCLUSION: The possible pathogenic mechanisms for this unusual
      presentation include hemorrhage into the cyst, sudden mechanical compression from
      abnormal spinal movement of a chronically distorted and compressed spinal cord,
      or an increase in the size of the cyst secondary to accumulation of cyst fluid.
      In this case a small increase in the cyst size may have resulted in increased
      mechanical distortion and spinal cord dysfunction on a compressive and ischemic
      basis.

PMID- 7627921
TI  - Brain herniation: a revision of classical concepts.
AB  - This paper is an update on evolving ideas about brain herniations. Following
      observations on cerebellar pressure coning that raised doubts about its reputed
      lethal connotations, herniation at the tentorium was re-examined for its role in
      critically damaging the brain stem. Combining clinical, pathologic, computed
      tomography and magnetic resonance imaging data, it is concluded that temporal
      lobe herniation is not the means by which the midbrain sustains irreversible
      damage in acute cases, but rather lateral displacement of the brain at the
      tentorium is the prime mover and herniation a harmless accompaniment.
      Transtentorial herniation has been investigated with computed tomography using
      the three calcification relationship and descent through the tentorial opening
      could not be documented. Bilateral brain stem compression in acute bilateral
      cases must be distinguished from herniation. Upward cerebellar herniation is only
      the sign of an overfull posterior fossa. Subfalcial herniation is tolerated
      unless lateral displacement is excessive.

PMID- 7627922
TI  - HIV-1 associated dementia: clinical features and pathogenesis.
AB  - HIV-1 infection is characterized by multiple neurological syndromes occurring at
      all stages of infection. HIV-1-associated dementia, however, is the most
      devastating CNS consequence of AIDS because of its poor prognosis and functional
      impairment. A clinical triad of progressive cognitive decline, motor dysfunction,
      and behavioural abnormalities typifies this subcortical dementia which eventually
      affects 15 to 20% of AIDS patients. Neuroimaging, CSF studies and
      neuropsychological testing are frequently required in diagnosing HIV-associated
      dementia, to exclude other conditions including psychiatric illnesses,
      opportunistic diseases and systemic disorders. The pathogenesis of HIV dementia
      is uncertain and there is evidence that multiple mechanisms of neurological
      injury occur. These mechanisms include: the role of neurovirulent strains of HIV;
      the potential neurotoxicity of HIV gp120, nitric oxide and quinolinic acid;
      immunologically mediated CNS injury through the action of cytokines and
      arachidonic acid metabolites; and altered blood-brain barrier permeability. A
      collective approach involving clinical studies, in vitro assays and animal models
      will provide greater insight into the pathogenesis and the rational development
      of therapy for HIV dementia.

PMID- 7627923
TI  - Understanding symptoms of schizophrenia.
AB  - In examining the heterogeneity of symptomatology in schizophrenia, several
      theoretical models have been advanced. These models are useful in understanding
      the psychopathology of the disease, as well as possibly guiding treatment and
      determining prognosis. This paper discusses the two-syndrome and three-syndrome
      models for the primary symptoms of schizophrenia and their relationship to other
      symptoms often encountered. In addition, their significance and relevance for
      treatment are explored.

PMID- 7627924
TI  - Integration of psychiatric rehabilitation in the long-term management of
      schizophrenia.
AB  - Psychiatric rehabilitation has been found to be a worthwhile conceptual framework
      in the long-term management of schizophrenia. It involves both pharmacotherapy
      and various psychosocial treatments. Psychiatric rehabilitation allows the
      treatment team to organize a comprehensive therapy plan for patients. This paper
      reviews the literature on psychiatric rehabilitation and describes an example of
      the practical application of these theories.

PMID- 7627925
TI  - Working with schizophrenia: a clinician's personal experience.
AB  - There are few mental illnesses that have as profound an effect on individuals and
      their families as schizophrenia. The management of patients with schizophrenia
      requires the clinician to be aware of the wide range of outcomes and the multiple
      facets of management that can be used. This article examines the variety of ways
      in which the physician can work with patients with schizophrenia to help them
      achieve their full potential.

PMID- 7627926
TI  - The long-term treatment of schizophrenia.

PMID- 7627927
TI  - Depot neuroleptic therapy: clinical considerations.
AB  - The management of schizophrenia is generally a long-term process with
      neuroleptics representing the cornerstone of treatment. Although not without
      their own limitations, depot neuroleptics offer an important alternative to oral
      agents, and they should be routinely considered as an option in any long-term
      treatment planning. The present article reviews depot neuroleptics, and focuses
      particularly on clinical considerations pertaining to their use.

PMID- 7627928
TI  - Molecular cytogenetics of human papillomavirus-negative cervical carcinoma cell
      lines.
AB  - Cervical cancer is a malignancy closely associated with human papillomavirus
      (HPV). However, some cervical carcinomas occur in the absence of the virus. Two
      HPV-negative cervical carcinoma cell lines, C-33A and HT-3, were examined by G
      banding and fluorescence in situ hybridization (FISH) using several whole
      chromosome and satellite probes. Combined conventional banding and FISH analysis
      significantly enhanced identification of complex and cryptic chromosome
      rearrangements. Common to both cell lines were translocations of chromosome 1,
      involving a specific site on the short arm and partial or complete loss of the
      short arm of chromosome 9, as well as loss of chromosome 13. The C-33A line had a
      relatively simple chromosomal constitution, with chromosome 1 being involved in
      translocations with chromosomes 9, 18, and 21. Karyotype reconstruction of G
      banded and painted chromosomes indicate a net loss of DNA as a result of
      unbalanced translocations, which occurred only at site 9p24 and loss of one copy
      of chromosomes 13 and 14. In contrast, HT-3 cells had complex rearrangements and
      deletions of chromosomes 1p, 3p, 9p, 10q/p, 11p/q, and 17p, all regions with
      known tumor suppressor genes. The deletions observed in these HPV-negative
      cervical carcinomas will be important in delineating regions of tumor suppressor
      genes.

PMID- 7627929
TI  - Characterization by chromosome painting of balanced and unbalanced X chromosome
      translocations in myelodysplastic syndromes.
AB  - Structural anomalies of the X chromosome, especially translocations, are rare
      events in myelodysplastic syndromes (MDS). In a series of 2270 MDS patients
      analyzed between 1983 and 1994 (Center for Human Genetics, Leuven), 9 cases were
      found with translocations involving the X chromosome. These aberrations were not
      restricted to specific FAB subtypes and were the sole anomalies in 3 cases. In
      the remaining 6 patients, they were associated with other abnormalities,
      including 5q-, observed in three cases. Fluorescence in situ hybridization (FISH)
      was retrospectively performed on 8 patients and was shown to be a useful
      complement for the characterization of the translocations involving the X
      chromosome. In 3 cases, we could identify translocation partners and breakpoint
      regions only by using chromosome painting. No recurrent chromosome partners were
      observed. The breakpoints could be localized along the whole X chromosome. There
      was, however, a cluster in the Xq13 region involved in 4 of the 9 patients. The
      previously reported association of Xq13 anomalies with refractory anemia with
      ringed sideroblasts (RARS) was found in only one case. Despite the lack of
      characteristic translocations involving the X chromosome, the occurrence of such
      changes as the sole karyotypic anomaly suggests that they could play a role in
      the pathogenesis of some myelodysplastic syndromes.

PMID- 7627930
TI  - Chromosome X numerical abnormalities in patients with non-Hodgkin's lymphoma. A
      study of 59 patients using fluorescence in situ hybridization.
AB  - Chromosome X numerical abnormalities are frequently observed in non-Hodgkin's
      lymphoma (NHL), with an incidence of 3% to 14% for chromosomal loss and 7% to 33%
      for chromosomal gain. Because sex chromosome numerical abnormalities are thought
      to be due to aging, little information is known about their relation to gender,
      therapy, and prognosis. Therefore, to determine the incidence and clinical
      relevance of this abnormality in NHL, we studied specimens from 59 NHL patients
      (31 men and 28 women) by fluorescence in situ hybridization (FISH) using a
      directly conjugated centromeric probe for chromosome X. The median age for the
      entire group was 52 years (range, 31-88 years). All specimens were obtained by
      fine-needle aspiration of diseased lymph nodes. Sex-matched lymphocytes from
      benign hyperplastic lymph nodes were used as controls. The overall incidence of
      chromosome X numerical abnormalities was 49.2%. Female patients had a higher
      overall incidence than males (76% vs. 24%; p < 0.001). The median percentage of
      cells involved in this abnormality in each specimen was 5.2%. There was no
      statistically significant difference in the incidence in previously treated than
      untreated patients (53.1% vs. 44.4%; p < 0.75) and in intermediate-grade NHL than
      low-grade NHL (61.1% vs. 50%; p < 0.75). There was a trend towards a higher
      incidence of chromosome X loss in older patients. While the difference in the
      incidence of chromosome X abnormalities observed between women and men may be due
      to the difference in the normal copy numbers of this chromosome in each sex
      group, this abnormality remained higher than any other autosomal chromosome
      abnormality in NHL previously evaluated by FISH. We conclude that, although FISH
      detected a high incidence of chromosome X numerical abnormalities and that
      females had a higher incidence than males, only a small percentage of the cells
      were involved, suggesting that this abnormality is most likely a secondary
      genetic defect that is not important in the pathogenesis of NHL.

PMID- 7627931
TI  - Primary cutaneous neuroendocrine tumors. Diagnostic use of cytogenetic and MIC2
      analysis.
AB  - Merkel cell carcinoma (MCC) is a primary cutaneous neoplasm most commonly
      involving older adults. The cell of origin is thought to be the Merkel cell, a
      cutaneous neurosecretory cell. However, other neuroectodermal tumors may present
      in the skin and may be difficult to distinguish from MCC, including peripheral
      neuroectodermal tumors (PNET) and metastatic small cell carcinoma. We examined a
      primary cutaneous tumor of an 18-year-old which was strongly positive for
      cytokeratin (CK), neuron-specific enolase (NSE), and 12E7, an antibody to the
      protein determined by the MIC2 gene. Electron microscopy showed paranuclear
      aggregates of filaments and no cytoplasmic processes. These findings were
      considered to be consistent with MCC. Cytogenetic analysis demonstrated
      46,XX,der(1)t(1;3;22)(1qter-->pa34::3q28-->q11::22q 12-->
      qter),der(3)t(1;3)(3pter-->q11::1p35-->pter), der(22)t(3;22)(22pter-->q11::?3q29-
      >qter). This was confirmed by chromosome painting using probes for chromosomes 1,
      3, and 22. Peripheral neuroectodermal tumors (PNETs) show a characteristic
      translocation involving the same breakpoint on chromosome 22 that was present in
      this tumor. PNETs can also be CK and NSE positive. The MIC2 gene codes for a
      surface glycoprotein that has been shown to be very strongly and reliably
      expressed in PNETs, but not in other small round blue cell tumors and not in
      small cell carcinoma of the lung. However, MIC2 expression has not been studied
      in MCC. We investigated the use of MIC2 analysis in the distinction of MCC from
      PNET. Five additional MCCs were stained with the monoclonal 12E7 antibody, and
      one additional tumor showed the strong membranous positivity reported in PNETs.
      Our data suggest that MIC2 analysis may be useful in differentiating between MCC
      and PNET. However, cases will remain for which the distinction is elusive and
      cytogenetic analysis may be helpful.

PMID- 7627933
TI  - Cytogenetic findings in 200 patients with multiple myeloma.
AB  - Cytogenetic studies were performed in 200 consecutive patients with multiple
      myeloma and related disorders. Structurally or numerically abnormal clones were
      found in 63 patients (32%), including 8 of 45 untreated patients (18%), and 55 of
      155 treated patients (35%). The abnormal karyotypes generally showed numerous
      numerical and structural aberrations and in some patients multiple abnormal
      clones. The most striking feature of patients with hyperdiploid karyotypes was
      the finding of consistent recurring trisomies for chromosomes 3, 5, 7, 9, 11, 15,
      19, and 21, cosegregating together in many cases. Monosomy for chromosome 13 was
      the most common chromosome loss, occurring in 18 abnormal patients (29%), while
      interstitial deletions involving band 13q14 occurred in an additional 9 patients,
      indicating a loss of all or part of chromosome 13 in a high percentage of
      patients with abnormal karyotypes (43%). Structural aberrations of chromosome 1
      were most frequent, occurring in 30 of 63 patients (48%), and involved almost
      equally the short and long arms. The single most frequent chromosome breakpoint
      involved band 14q32 and was found in 21 patients (33%), including 11 patients
      with a 14q+ chromosome, 8 with t(11;14)(q13;q32), and 2 with t(8;14)(q24;132).

PMID- 7627932
TI  - p53 gene mutations with chromosome 17 abnormalities in chronic myelogenous
      leukemia blast crisis patients persist in long-term cell lines but may be
      acquired in acute myeloid leukemia cells in vitro.
AB  - Altered p53 tumor suppressor genes have been described in various human
      malignancies, including in chronic myelogenous leukemias (CML) and acute
      myelogenous leukemias (AML), as well as their derivative cell lines. It has been
      proposed that this gene mutation may be less frequent in myeloid leukemia
      patients than in myeloid leukemia cells lines and that the latter acquire these
      mutations during growth in vitro. We investigated this possibility by studying
      p53 gene alterations in matched samples of fresh leukemic cells and their
      respective derivative cell lines obtained from two CML blast crisis and one AML
      patient. No gross structural abnormalities were detected in the p53 gene in any
      of the samples analyzed. Discrete mutations in the gene in the two CML blast
      crisis samples and in all three derivative cell lines were, however, detected by
      polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP)
      analyses and DNA sequencing. Cytogenetic analyses revealed either numerical or
      structural, as well as numerical, abnormalities of chromosome 17 in their
      karyotypes. Cells from the two CML blast crisis patients had two different
      mutations which were maintained as the sole mutations in the cell lines. The
      mutation detected in the AML cell line was, however, not detectable in the
      parental fresh leukemic cells. Our findings demonstrate that p53 mutations and
      chromosome 17 abnormalities occurring in CML blast crisis patients persist in
      long-term cell lines but that mutations not detectable in AML patients may indeed
      be acquired in cell lines established from them in vitro.

PMID- 7627934
TI  - A search for double minute chromosomes in cultured lymphocytes from different
      types of tumors.
AB  - Double minutes are considered the products of DNA amplification and are rare in
      normal human cells. They have been observed in cultured lymphocytes in selected
      samples of human populations as one of the characteristics of the so-called rogue
      cells. We scored 9500 metaphases of cultured lymphocytes from 65 subjects with a
      variety of heredity and sporadic tumors and from 30 healthy subjects. The 15
      cells with double minutes were found in subjects with multiple endocrine
      neoplasia type 1 (14 cases) and with familial adenomatous polyposis (1 case).
      Only one rogue cell was found among the 15 cells with double minutes.

PMID- 7627935
TI  - A unique chromosome translocation, t(11;12;18)(q21;q13;q21) [correction of
      t(11;12;18)(q13;q13;q12)], in primary lung lymphoma.
AB  - A 54-year old man with a primary lung lymphoma of mucosa-associated lymphoid
      tissue (MALT) origin whose tumor cells had a t(11;12;18)(q13;q13;q12) chromosome
      abnormality is described. The morphologic, immunologic, and molecular biologic
      investigations showed that the patient's lung tumor consisted of small lymphoid
      cells that expressed monoclonal IgM, kappa-type immunoglobulin, and
      immunoglobulin gene (JH and C kappa) rearrangements. Cytogenetic study revealed
      that the tumor cells contained a unique chromosome translocation,
      t(11;12;18)(q13;q13;q12), that has not been reported previously in lymphoma.

PMID- 7627936
TI  - An important role for chromosome 17, band q25, in the histogenesis of alveolar
      soft part sarcoma.
AB  - A cytogenetic study of two cases of alveolar soft part sarcoma showed near
      diploid karyotypes with multiple chromosomal rearrangements. An abnormality of
      the long arm of chromosome 17, involving band q25, is present in both cases and
      in 2 of 4 cases in the literature. This recurrent structural abnormality probably
      plays an important role in the histogenesis of this unusual neoplasm and
      therefore is important for further molecular investigation.

PMID- 7627937
TI  - Chromosome 12 abnormalities in malignant ovarian germ cell tumors.
AB  - We analyzed 3 cases of malignant ovarian germ cell tumors (MOGCTs), comprising 1
      dysgerminoma and 2 immature teratomas, by banded chromosome analysis and by in
      situ hybridization (ISH) using a chromosome 12p painting probe. We found evidence
      of 12p abnormalities in two of them. A possible common genetic pathway of origin
      of a subset of MOGCTs with testicular germ cell tumors (TGCTs) is discussed.

PMID- 7627938
TI  - Translocation (5;19)(q13;q13) in a multinodular thyroid goiter.
AB  - We describe the cytogenetics of a multinodular thyroid goiter where 90% of the
      analyzed cells showed a diploid karyotype with a balanced translocation between
      chromosomes 5 and 19: 46,XX,t(5;19)(q13;q13). This translocation has been
      previously described in cases of thyroid adenoma. Our case is the first report of
      this anomaly in nodular hyperplasia. We discuss its putative role in the
      neoplastic transformation of thyroid lesions.

PMID- 7627939
TI  - Biclonal acute monoblastic leukemia showing del(7q) and trisomies 9 and 22.
AB  - Cytogenetic biclonality is a rare phenomenon in acute myeloid leukemia. We report
      a case of acute monoblastic leukemia with biclonal cytogenetic abnormalities,
      showing an abnormal clone with an unusual occurrence of trisomy 9 and trisomy 22,
      in addition to a second clone with deletion of the long arm of chromosome 7 as
      the only abnormality. The significance of these findings in leukemogenesis is
      discussed.

PMID- 7627940
TI  - Translocational rearrangements of 11q23 in acute monoblastic leukemia.
AB  - We report the rearrangements of 11q23 in the form of t(6;11)(q27;q23) and
      t(11;16)(q23;q24) in three cases of acute monoblastic leukemia. The former
      translocation had only previously been reported in five cases of acute myeloid
      leukemia, while the latter is hitherto undescribed. In addition to describing a
      new chromosomal locus 16q24, which may participate in translocational exchanges
      with 11q23, this report also confirms the close association between 11q23
      rearrangement and the involvement of the monocytic lineage in acute myeloid
      leukemia.

PMID- 7627941
TI  - Trisomy 12 does not correlate with EBV infection in chronic B-cell leukemias.

PMID- 7627942
TI  - Trisomy 7 as the sole cytogenetic aberration in the epithelial component of a
      colonic adenoma.

PMID- 7627943
TI  - Cytogenetic characterization of an iris melanoma.

PMID- 7627944
TI  - Translocation (1;22)(q11;p11) in a case of early pre-B cell ALL.

PMID- 7627945
TI  - Comparative genomic hybridization in acute myeloid leukemia. A comparison with G
      banding and chromosome painting.
AB  - Comparative genomic hybridization (CGH) represents a new technique for global
      analysis of a whole genome for net loss or gain of chromosome regions. It offers
      several advantages over alternative techniques. It permits analysis of a whole
      genome in a single hybridization reaction, it does not require the generation of
      metaphases from tumor cells, and it only requires very small numbers of tumor
      cells. Most previous studies have concentrated on the application of CGH to the
      analysis of chromosome defects associated with solid tumors. In this paper we
      report the use of CGH to study bone marrow samples from a patient with acute
      myeloid leukemia and complex karyotypic abnormalities. The results obtained using
      CGH were compared with G-banding analysis. Both G-banding and CGH detected a 5q
      deletion, a 7q deletion, additional material derived from 8q, and an HSR on 11q.
      However, several apparently discrepant results were also obtained. Paints for
      chromosomes 3, 5, 7, 8, 11, 12, 14, 17, 22, and X were therefore used to resolve
      these differences. Our results demonstrate that CGH detected chromosome
      abnormalities associated with acute myeloid leukemia and that CGH provided
      information that was not obtained by G-banding analysis alone. These data suggest
      that CGH may prove a useful adjunct to conventional cytogenetic and molecular
      analysis of hematologic malignancies.

PMID- 7627946
TI  - Acute lymphoblastic leukemia in a patient with familial derivative chromosome 4.

PMID- 7627947
TI  - Duplication of N-MYC at its resident site 2p24 may be a mechanism of activation
      alternative to amplification in human neuroblastoma cells.
AB  - Amplification of the human N-MYC proto-oncogene is frequently seen either in
      extrachromosomal double minutes or in homogeneously staining regions of
      aggressively growing neuroblastomas. N-MYC maps to chromosome 2 band p23-24, but
      homogeneously staining regions have never been observed at this band, suggesting
      transposition of N-MYC during amplification. Previous studies had suggested that
      in cells with amplified N-MYC the chromosomes 2 appear to be unaltered and to
      carry one apparently normal copy of N-MYC each. In contrast, the contribution of
      N-MYC to tumors which lack amplification has been unclear. We here show, by
      fluorescence in situ hybridization, that N-MYC is occasionally duplicated at its
      resident site in neuroblastoma cell lines previously thought to have a single
      copy gene. Additionally, we detected duplication in a neuroblastoma cell line
      carrying amplification. Our results raise the possibility that duplication may,
      in some neuroblastomas, either be a prelude to amplification or an alternative
      pathway by which N-MYC becomes activated.

PMID- 7627948
TI  - Heterogeneity of deletions involving RB-1 and the D13S25 locus in B-cell chronic
      lymphocytic leukemia revealed by fluorescence in situ hybridization.
AB  - Recently, the D13S25 locus, which is in close proximity to the retinoblastoma
      gene (RB-1) on chromosome band 13q14, was discussed to play a role in the
      pathogenesis of B-CLL. In the present study, we isolated two overlapping genomic
      DNA clones (termed c13S25) containing the D13S25 DNA segment and used them as
      probes to analyze 85 B-CLL cases by fluorescence in situ hybridization; of the 55
      cases with two RB-1 copies, 13 exhibited hemizygous (n = 7) or homozygous (n = 6)
      deletion of D13S25. Of 29 cases with hemizygous deletion of RB-1, all but two
      also showed loss of D13S25 (hemizygous, n = 25; homozygous, n = 2). One case had
      a homozygous deletion of both loci. We conclude that deletion of D13S25 occurs in
      a substantial number of B-CLL without deletion of RB-1. However, in some cases
      there is deletion of RB-1 without loss of D13S25, suggesting that D13S25 is not
      the locus of the putative tumor suppressor gene. According to our data, such a
      gene is most likely located within the genomic region between D13S25 and RB-1.

PMID- 7627949
TI  - Identification of MAGE-1 and MAGE-4 proteins in spermatogonia and primary
      spermatocytes of testis.
AB  - The MAGE genes encoding tumor rejection antigens recognized by CTLs are expressed
      at the mRNA level in various cancers and in the testis but not in the other
      normal tissues. The expression of MAGE-1 or MAGE-4 protein in the testicular
      cells was studied immunohistochemically with the antibodies to the recombinant
      MAGE-1 or MAGE-4 protein. Both proteins were identified in the nucleus and
      cytoplasm of spermatogonia and in primary spermatocytes but not in spermatids or
      Sertoli's cells. Therefore, MAGE proteins are normal tissue antigens
      compartmentalized in particular testicular cells playing an important role in the
      early phase of the spermatogenesis.

PMID- 7627951
TI  - The induction of cytotoxic T cells and tumor regression by soluble antigen
      formulation.
AB  - CTLs specific for tumor antigens play a major role in the immunity against
      cancer. We have shown that class I-restricted CTLs can be induced by injecting
      soluble antigens mixed in an antigen formulation (AF) that consists of squalane,
      Tween 80, and Pluronic L121 (S. Raychaudhuri et al., Proc. Natl. Acad. Sci. USA,
      89: 8308-8312, 1992). In this study, using ovalbumin and the ovalbumin-expressing
      transfectoma (EG7) as a tumor model system, we examined the in vivo antitumor
      effect of antigen-AF mixture. Vaccination of mice with ovalbumin in AF 2 or 3
      days after EG7 tumor challenge showed significant inhibition of tumor growth
      compared to mice vaccinated with ovalbumin in alum or in saline. Depletion of
      CD8+ cells at the time of immunization completely abrogated the AF-induced tumor
      protection, indicating that CD8+ T cells are the major effectors in tumor
      protection in vivo. Depletion of CD4+ cells led to a marginal loss of tumor
      protection, which may be the result of inhibition of ovalbumin-specific CTL
      response due to the lack of T-helper activity. Our results demonstrate that AF
      can be used in subunit vaccines to stimulate CTLs and tumor regression in vivo.

PMID- 7627950
TI  - Cytochrome P4501A1 and glutathione S-transferase (M1) genetic polymorphisms and
      postmenopausal breast cancer risk.
AB  - Polycyclic aromatic hydrocarbons, possible human breast carcinogens, are
      metabolized by cytochrome P4501A1 (CYP1A1) and glutathione S-transferase (GSTM1).
      A CYP1A1 polymorphism (isoleucine to valine substitution in exon 7) or the null
      allele for GSTM1 may affect the mutagenic potential of polycyclic aromatic
      hydrocarbons. We examined polymorphisms in GSTM1 and CYP1A1 in relation to breast
      cancer risk. Included were 216 postmenopausal Caucasian women with incident
      breast cancer and 282 community controls. DNA analyses suggested no increased
      breast cancer risk with the null GSTM1 genotype [odds ratio (OR) = 1.10; CI, 0.73
      1.64], although there was some indication that the null genotype was associated
      with risk among the youngest postmenopausal women (OR = 2.44; CI, 0.89-6.64).
      Slightly elevated risk was associated with the CYP1A1 polymorphism (OR = 1.61;
      CI, 0.94-2.75) and was highest for those who smoked up to 29 pack-years (OR =
      5.22; CI, 1.16-23.56). Statistical power to detect an effect may be limited by
      small numbers, and larger sample sizes would be required to corroborate these
      suggestive findings.

PMID- 7627952
TI  - Microinjection of monoclonal antibody PAb421 into human SW480 colorectal
      carcinoma cells restores the transcription activation function to mutant p53.
AB  - The p53 tumor suppressor is a transcription factor frequently mutated in human
      malignancies. Tumor-derived p53 missense mutants are defective in sequence
      specific DNA binding and fail to activate p53 target genes. mAb PAb421 was shown
      previously to restore DNA binding to selected p53 mutants in vitro. Here we show
      that mAb PAb421 when microinjected into human SW480 colorectal carcinoma cells
      restores the transcription activation function to the resident mutant p53 (arg to
      his 273, pro to ser 309). Codon 273 is the second most frequent p53 missense
      mutant found in human tumors. Our results lend support to the concept of
      restoring wild-type function to mutant p53 as a strategy for cancer therapy.

PMID- 7627953
TI  - Aberrant expression of the growth factor Wnt-5A in human malignancy.
AB  - The Wnt-5A gene codes for a secreted cysteine-rich growth factor that mediates
      cell to cell signaling via a paracrine mechanism during development and ontogeny.
      We have recently determine the genomic organization and chromosomal mapping of
      the human Wnt-5A, and observed distinct patterns of expression in developing
      human embryos. In this report, we have performed a detailed expression analysis
      of 100 adult human tissues and tumors and 10 human cell lines. Our data show a
      widespread expression of Wnt-5A in adult tissues and cells, and aberrant mRNA
      levels in lungs, breast, and prostate carcinomas and in melanomas. The up
      regulation of Wnt-5A in human malignancy was not due to either gene rearrangement
      or amplification. These findings document an abnormal expression of this growth
      factor in malignancy and implicate Wnt-5A in the genesis of human cancer.

PMID- 7627954
TI  - Point mutation of ornithine decarboxylase gene in human hepatocellular carcinoma.
AB  - Ornithine decarboxylase (ODC) plays an important role in cell growth, and its
      activity is regulated by many mechanisms. The biochemical characteristics of ODC
      in malignant cells differ from those of ODC in normal cells. To determine whether
      novel changes occur in ODC in neoplastic tissue, we compared the nucleotide
      sequence of ODC cDNA obtained from human hepatoma tissue as determined by reverse
      transcriptase-PCR with that of ODC cDNA obtained from nontumorous tissue in the
      same patients. There were three point mutations accompanied by replacements of
      amino acids in hepatoma tissue with other amino acids or a stop codon. In one
      poorly differentiated hepatoma, codon 415, CAA was converted to TAA, resulting in
      replacement of Gln-415 by a stop codon. The mutated ODC protein produced by
      translation in a reticulocyte-lysate protein synthesizing system was truncated
      and stabilized in an ATP antizyme-dependent degradation system. These findings
      suggest that formation of a truncated and stabilized ODC protein due to point
      mutation is one reason why ODC activity is high in human hepatoma tissue.

PMID- 7627955
TI  - Beta-adrenergic mitogenic signal transduction in peripheral lung adenocarcinoma:
      implications for individuals with preexisting chronic lung disease.
AB  - Peripheral adenocarcinoma (PAC) of the lung has increased dramatically over the
      last 20 years and is today the leading histological type of lung cancer in
      smokers and nonsmokers in industrialized countries. There is no apparent
      explanation for the steep rise in the number of individuals developing this
      cancer type. Using assays for the assessment of cell proliferation, receptor
      binding, and production of cyclic AMP (cAMP), we have identified a beta
      adrenergic receptor-mediated mitogenic pathway, which activates cAMP down-stream,
      in cell lines derived from human peripheral adenocarcinomas that express features
      of Clara cells. Agonists of beta-adrenergic receptors strongly stimulated cell
      proliferation, whereas antagonists of this receptor and its associated second
      messenger, cAMP, were potent inhibitors of this effect. Agonists of beta
      adrenergic receptors are the active ingredients of many decongestants and
      bronchodilators, and such medications are, therefore, likely to stimulate this
      pathway in vivo. Patients suffering from chronic upper and lower respiratory
      tract diseases and treated with such medications over many years may, therefore,
      be at a higher risk than the average population to develop PAC, particularly when
      simultaneously exposed to carcinogenic environmental factors such as smoking.
      Because the incidence of chronic respiratory tract diseases has risen in
      industrialized countries during the same time frame as PAC, a potential
      etiological link between the therapy of such nonneoplastic diseases with beta
      adrenergic agonists and the risk for PAC should be investigated.

PMID- 7627956
TI  - Thrombopoietin receptor expression in human cancer cell lines and primary
      tissues.
AB  - c-mpl is the receptor for the recently identified megakaryocyte growth and
      differentiation factor thrombopoietin. Thrombopoietin has been shown to be
      capable of raising platelet counts in animals and is about to enter clinical
      trials in humans. In anticipation of its likely use in the care of patients
      receiving cancer chemotherapy, we evaluated the expression of human c-mpl by
      reverse transcription PCR on 39 human cell lines and 20 primary human tissue
      samples derived from both normal and malignant sources. c-mpl transcripts were
      found in all megakaryocytic cell lines tested (CMK, CMK-2B, CMK-2D, SO, and
      DAMI), the CD34+ leukemia cell line KMT-2, and a hepatocellular carcinoma cell
      line (Hep3B). Among primary tissues, fetal liver cells and brain had detectable
      levels of c-mpl message, and among primary tumors, none were found to express c
      mpl. These data support the conclusion that c-mpl has restricted expression that
      is primarily, but not exclusively, related to megakaryocytopoiesis. These
      observations suggest that thrombopoietin is unlikely to have direct effects on
      other malignant or normal tissue should it have a clinical role in the treatment
      of chemotherapy-induced thrombocytopenia.

PMID- 7627957
TI  - Cell-type-specific ras mutations but no microsatellite instability in chemically
      induced mouse skin tumors and transformed 3T3 cells.
AB  - In mouse skin, both papillomas/carcinomas or fibrosarcomas can be induced by 7,12
      dimethylbenz[alpha]anthracene (DMBA) depending on the mode of administration.
      Thus, upon DMBA painting (or transplacental exposure by i.p. injection to
      pregnant mothers) followed by 12-O-tetradecanoylphorbol-13-acetate applications
      to the skin of CD1 mice, papillomas and carcinomas appeared, whereas
      fibrosarcomas were induced when DMBA was s.c. injected. Molecular analysis of
      these tumors revealed that the majority of papillomas (17/20) and carcinomas
      (9/10) showed DMBA-specific mutations (A to T transversion at the 61st codon) in
      the Ha-ras gene. On the other hand, many fibrosarcomas (5/9) showed the same
      mutation only in the Ki-ras gene. When microsatellites were studied in these
      tumors at nine loci containing CA repeats, none of them showed an instability. In
      addition, when we analyzed 14 BALB/c 3T3 cell lines transformed by various
      carcinogens (including 3 clones induced by DMBA which have the A to T mutation in
      the Ki-ras gene), no changes in CA repeats were observed. These results suggest
      that DMBA-induced mouse tumors/transformed cells show cell-type-specific ras gene
      mutations, and these occur independently in the absence of microsatellite
      instability. While murine cells are considered to be relatively susceptible to
      cancer induction partially due to genomic instability, our results indicate that
      microsatellite instability is not induced in these cells by chemical carcinogens.

PMID- 7627958
TI  - Germline mutation of BRCA1 in Japanese breast cancer families.
AB  - We analyzed germline mutations of the BRCA1 gene in 18 Japanese breast cancer
      families and two Japanese breast-ovarian cancer families. In two site-specific
      breast cancer families, the same mutation was detected; a nonsense mutation at
      codon 63 encoding a truncated small protein. It was demonstrated that the mutant
      allele cosegregated with breast cancer patients within a family and was absent in
      healthy Japanese, suggesting a breast cancer-predisposing allele. The average age
      at diagnosis was 44 and 55 years in each family with BRCA1 mutation. No bilateral
      breast cancer patients were present in the BRCA1 mutation-positive families,
      although five were present in the BRCA1-negative families. No germline mutations
      of BRCA1 were detected in the two breast-ovarian cancer families examined in this
      study, although BRCA1 mutation plays a major role in breast-ovarian cancer
      families in Western countries. Thus, the proportion of families who inherit the
      mutated BRCA1 allele seems to be small among Japanese breast cancer families and
      Japanese breast-ovarian cancer families.

PMID- 7627959
TI  - Enhanced hepatic amino acid transport in tumor-bearing rats is partially blocked
      by antibody to tumor necrosis factor.
AB  - The liver of the host with cancer exhibits an enhanced requirement for amino
      acids to support tumor-induced increases in hepatic protein synthesis and
      gluconeogenesis. To address the mechanism by which the liver ensures adequate
      delivery of these substrates for intracellular utilization during cancer, we
      studied the activities of several amino acid transporters in hepatic plasma
      membrane vesicles prepared from rats implanted with a rapidly growing s.c.
      fibrosarcoma. The presence of the tumor resulted in a generalized stimulation of
      concentrative (Na(+)-dependent) glucogenic (small neutral) amino acid uptake via
      System A (3.4-fold), System N (2.3-fold), and System ASC (1.7-fold), as well as
      in the facilitative (Na(+)-independent) uptake of arginine via System y+ (1.7
      fold). Kinetic analysis revealed that the tumor-induced enhancement of transport
      activity was due to increases in the maximum transport velocity (Vmax), whereas
      transporter substrate affinities (Km) did not change significantly.
      Administration of antibody to tumor necrosis factor-alpha to tumor-bearing rats
      attenuated the increase in hepatic amino acid transport activity by 60-100%.
      Treatment of nontumor-bearing control rats with tumor necrosis factor-alpha mAb
      did not alter basal transport activity. The results from these studies suggest
      that the tumor elicits a generalized increase in hepatic plasma membrane amino
      acid transport activity via a pathway that involves the cytokine tumor necrosis
      factor.

PMID- 7627960
TI  - Metabolic activation of N-hydroxyarylamines and N-hydroxyarylamides by 16
      recombinant human NAT2 allozymes: effects of 7 specific NAT2 nucleic acid
      substitutions.
AB  - Human polymorphic N-acetyltransferase (NAT2) catalyzes the N-acetylation of
      arylamine carcinogens and the metabolic activation of N-hydroxyarylamine and N
      hydroxyarylamide carcinogens by O- and N,O-acetylation, respectively. Rapid and
      slow acetylator phenotype is regulated at the NAT2 locus, and each has been
      associated with differential risk to certain cancers relating to carcinogenic
      arylamine exposures. We examined arylamine N-acetylation, N-hydroxyarylamine O
      acetylation, and N-hydroxyarylamide N,O-acetylation catalytic activities of 16
      different recombinant human NAT2 alleles expressed in an Escherichia coli JM105
      expression system. NAT2 alleles contained nucleic acid substitutions at G191A
      (Arg64-->Gln), C282T (silent), T341C (Ile114-->Thr), C481T (silent), G590A
      (Arg197-->Gln), A803G (Lys268-->Arg), G857A (Gly286-->Glu), and various
      combinations of substitutions in the 870-bp NAT2-coding region. Expression of
      each NAT2 allele produced equivalent amounts of immunoreactive recombinant NAT2
      protein with differential levels of N-, O-, and N,O-acetylation activity.
      Catalytic activities of each of the recombinant human NAT2 allozymes followed the
      relative order N-acetylation > O-acetylation > N,O-acetylation. Catalytic
      activation rates for the metabolic activation of N-hydroxy-2-aminofluorene and N
      hydroxy-4-aminobiphenyl by O-acetylation and N-hydroxy-2-acetylaminofluorene by
      N,O-acetylation showed very strong correlations to the N-acetylation of 2
      aminofluorene. NAT2 alleles with nucleic acid substitution T341C
      (NAT2*5A,*5B,*5C) expressed recombinant NAT2 allozymes, with the greatest
      reductions in metabolic activation of N-hydroxyarylamines and N-hydroxyarylamides
      by O- and N,O-acetylation, respectively. NAT2 alleles with nucleic acid
      substitutions G191A (NAT2*14A,*14B) and G590A (NAT2*6A,*6B) expressed recombinant
      NAT2 allozymes with more moderate reductions. NAT2 alleles with nucleic acid
      substitution G857A (NAT2*7A,*7B) expressed recombinant NAT2 allozymes with the
      smallest but yet significant reductions. NAT2 alleles with nucleic acid
      substitutions C282T (silent), C481T (silent), and A803G (Lys268-->Arg) expressed
      recombinant NAT2 allozymes that did not have significant reductions in the
      metabolic activations of N-hydroxyarylamines and N-hydroxyarylamides. The
      differential capacity for the metabolic activation of N-hydroxyarylamines and N
      hydroxyarylamides by recombinant human NAT2 allozymes encoded by polymorphic NAT2
      alleles supports the hypothesis that acetylator phenotype may predispose to
      cancers related to activation of N-hydroxy-arylamine and N-hydroxyarylamide
      carcinogens.

PMID- 7627961
TI  - Polyadenylation polymorphism in the acetyltransferase 1 gene (NAT1) increases
      risk of colorectal cancer.
AB  - Exposure to carcinogens present in the diet, cigarette smoke, or the environment
      may be associated with increased risk of colorectal cancer. Aromatic amines (aryl
      and heterocyclic) are a class of carcinogens that are important in these
      exposures. These compounds can be N- or O-acetylated by the NAT1 or NAT2 enzymes,
      resulting in activation or in some cases detoxification. Recent studies have
      shown that both NAT2 and NAT1 genes exhibit variation in human populations and
      that rapid acetylation by the NAT2 enzyme may be a risk factor for colorectal
      cancer. In this study we have analyzed for genetic polymorphism in both NAT1 and
      NAT2 in a group of 202 colorectal cancer patients and 112 control subjects from
      Staffordshire, England. We find significantly increased risk (odds ratio, 1.9;
      95% confidence interval, 1.2-3.2; P = 0.009) associated with the NAT1*10 allele
      of NAT1, an allele that contains a variant polyadenylation signal. Individuals
      with higher stage tumors (Duke's C) were more likely to inherit this variant
      allele (odds ratio, 2.5; 95% confidence interval, 1.3-4.7; P = 0.005). In
      contrast, rapid acetylation genotypes of NAT2 were not a significant risk factor
      in this English population. However, we found that the risk associated with the
      NAT1 variant allele (NAT1*10) was most apparent among NAT2 rapid acetylators
      (odds ratio, 2.8; 95% confidence interval, 1.4-5.7; P = 0.003), suggesting a
      possible gene-gene interaction between NAT1 and NAT2 (test for interaction; P =
      0.12). This is the first study to test for cancer risk associated with the NAT1
      gene, and these positive findings suggest that NAT1 alleles may be important
      genetic determinents of colorectal cancer risk.

PMID- 7627962
TI  - 5-Ethoxy-2'-deoxyuridine, a novel substrate for thymidine phosphorylase,
      potentiates the antitumor activity of 5-fluorouracil when used in combination
      with interferon, an inducer of thymidine phosphorylase expression.
AB  - Clinical studies have demonstrated that the combination of 5-fluorouracil (FUra)
      and IFN-alpha has activity in the treatment of advanced colorectal cancer.
      Treatment of human colon carcinoma cells with IFN caused a 5-fold increase in the
      level of thymidine phosphorylase (TP) mRNA and an 8-fold increase in TP enzyme
      activity. Since TP catalyzes the first step in the direct conversion of FUra to
      deoxyribonucleotides, its induction by IFN is a potential biochemical mechanism
      for the modulation of the antitumor activity of FUra. In contrast to the activity
      measured in cell extracts, however, thymine utilization by intact cells was
      increased less than 2-fold by IFN, suggesting that the metabolic activation of
      FUra by TP in the IFN-treated cells was similarly suboptimal. This was likely due
      to a rate-limiting amount of cosubstrate for TP, and in this study, a series of 5
      substituted 2'-deoxyuridine analogues were synthesized and tested as potential
      deoxyribose donors for TP. One of the compounds, the novel pyrimidine analogue 5
      ethoxy-2'-deoxyuridine (EOdU), was found to be a substrate for the transferase
      reaction of TP, to have little or no direct cytotoxicity, to selectively increase
      the cellular levels of 5-fluoro-dUMP, to enhance the inhibitory effect of FUra on
      thymidylate synthase activity, and to potentiate the cytotoxicity of FUra and IFN
      in human colon carcinoma cells. EOdU was tested in vivo against HT-29 cells grown
      as xenografts in nude mice. The combination of EOdU+FUra+IFN-alpha 2a produced
      tumor regressions and a significantly greater delay in tumor growth when compared
      to FUra+IFN-alpha 2a, FUra+EOdU, or FUra or IFN used alone; tumors were 72%
      smaller in the EOdU+FUra+IFN-alpha 2a-treated animals compared to the saline
      control group. A comparable antitumor effect was also found when a related
      nucleoside analogue, 5-propynyloxy-2'-deoxyuridine, was used with FUra+IFN, and
      it also showed modulating activity when used with only FUra. The antitumor
      activity of the three agent combination (nucleoside+IFN+FUra) was comparable to
      that of a higher dose of FUra used alone, but it was substantially less toxic to
      the animals than the higher dose of FUra, indicating that the modulating agents
      improved the therapeutic index of FUra.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7627963
TI  - Bisphosphonate risedronate reduces metastatic human breast cancer burden in bone
      in nude mice.
AB  - Human breast cancer frequently metastasizes to the skeleton to cause osteolysis
      and subsequent pain, pathological fracture, and hypercalcemia. Because bone
      continuously releases growth factors stored in bone matrix by bone resorption
      during physiological remodeling and, thus, possibly provides a favorable
      microenvironment for metastatic breast cancer cells to proliferate, inhibitors of
      bone resorption used either prophylactically or in patients with established
      disease, therefore, would seem likely to be useful adjuvant therapy in patients
      with breast cancer. However, the parameters for monitoring progressive osteolytic
      bone disease in humans are imprecise. We examined the effects of the third
      generation bisphosphonate, risedronate, which is a specific inhibitor of
      osteoclastic bone resorption, in a bone metastasis model in nude mice in which
      intracardiac injection of the human breast cancer cell line MDA-231 leads to
      osteolytic bone metastases. Risedronate (4 micrograms/animal/day) was given s.c.
      to animals (a) after radiologically small but defined osteolytic metastases were
      observed; (b) simultaneously with MDA-231 cell inoculation through the entire
      experimental period; or (c) by short-term prophylactic administration before
      inoculation of MDA-231 cells. In all experiments, risedronate either slowed
      progression or inhibited the development of bone metastases assessed
      radiographically. Furthermore, mice treated continuously with risedronate showed
      significantly longer survival than did control mice. Histomorphometrical analysis
      revealed that osteoclast numbers were diminished at metastatic tumor sites.
      Unexpectedly, there was also a marked decrease in tumor burden in bone in
      risedronate-treated animals. In contrast, the growth of metastatic breast cancer
      in soft tissues surrounding bones was not affected by risedronate. Moreover,
      risedronate had no effects on the local growth of s.c. implanted MDA-231 breast
      cancers in nude mice or on MDA-231 cell proliferation in culture. These data
      demonstrate that risedronate decreases metastatic MDA-231 breast cancer burden
      selectively in bone, as well as suppresses progression of established osteolytic
      lesions and prevents the development of new osteolytic lesions; thus, the data
      suggest that inhibition of osteoclastic bone resorption may be a useful
      adjunctive therapy for the treatment of cancers that have colonized in bone.

PMID- 7627964
TI  - Regressions and cures of melanoma xenografts following treatment with monoclonal
      antibody beta-lactamase conjugates in combination with anticancer prodrugs.
AB  - Cephalosporin doxorubicin (C-Dox) and 7-(4-carboxybutanamido)-cephalosporin
      mustard (CCM) are prodrugs that are catalytically converted by Enterobacter
      cloacae beta-lactamase (bL) to the active anticancer agents doxorubicin and
      phenylenediamine mustard, respectively. Both prodrugs were less cytotoxic to the
      3677 human melanoma line than their respective drugs and were activated in an
      immunologically specific manner by 96.5-bL, a mAb-bL conjugate that binds to 3677
      cell surface antigens. Similar results were obtained using the CCM prodrug on SK
      MEL 28 human melanoma cells. Experiments in mice with established s.c. 3677
      tumors demonstrated that although no tumors were cured in mice receiving the 96.5
      bL/C-Dox combination, the activities were greater than those obtained from
      systemic doxorubicin treatment or from administration of the nonbinding conjugate
      P1.17-bL in combination with C-Dox. In contrast, when CCM was used as a prodrug,
      cures of established 3677 tumors were obtained in 80% of the 96.5-bL treated
      animals. This combination was also able to induce regressions of large 3677 tumor
      masses (800 mm3) without any apparent toxic side effects. We conclude that 96.5
      bL in combination with C-Dox or CCM has greater antitumor activity than systemic
      treatment with the corresponding drugs and that CCM is a more effective prodrug
      than C-Dox for treating human 3677 melanoma xenografts.

PMID- 7627965
TI  - Role of reoxygenation in induction of enhancement of tumor radioresponse by
      paclitaxel.
AB  - We reported previously (L. Milas et al., Cancer Res., 54: 3506-3510, 1994) that
      paclitaxel greatly enhances the response of a murine mammary carcinoma to
      subsequent irradiation and hypothesized that the enhanced radioresponse was
      mediated by tumor cell reoxygenation caused by treatment with paclitaxel. Because
      paclitaxel induced massive tumor cell destruction by apoptosis, it was reasoned
      that as apoptotic cells were removed from the tumor more hypoxic cells would have
      access to oxygen, be reoxygenated, and, thus, become more sensitive to radiation.
      The present study tested this hypothesis by assessing the effect of 60 or 40
      mg/kg paclitaxel on radioresponse of an 8-mm MCA-4 tumor irradiated under air
      breathing or hypoxic conditions 9, 24, 48, or 72 h after paclitaxel
      administration. If the hypothesis was correct, paclitaxel would enhance tumor
      radioresponse more under air breathing than under hypoxic conditions, and the
      enhancement would increase as the time between paclitaxel administration and
      tumor irradiation increased within a few days after paclitaxel treatment but only
      when radiation was given under air-breathing conditions. The effect of the
      treatments was determined by tumor growth delay and the radiation dose required
      to control 50% of the tumors (TCD50). Paclitaxel greatly enhanced tumor
      radioresponse under air-breathing (and not hypoxic) conditions, increasing tumor
      growth delay, and reducing TCD50. These effects increased as the time interval
      between paclitaxel administration and tumor irradiation increased within the
      observation period of 72 h after paclitaxel treatment. The enhancement factors
      for tumor growth delay ranged from 1.19 at 9 h to 1.86 at 48 h and for TCD50,
      from 1.16 at 9 h to 1.47 at 72 h after paclitaxel. Direct measurements of tumor
      pO2 showed a median value in untreated tumors of 6.2 mmHg, which increased to
      10.5 mmHg at 24 h and to 31.2 mmHg at 48 h after paclitaxel administration.
      Overall, these results show that paclitaxel is a potent enhancer of tumor
      radioresponse and that its effect is mediated by reoxygenation of hypoxic tumor
      cells.

PMID- 7627966
TI  - Farnesyltransferase inhibitors block the neurofibromatosis type I (NF1) malignant
      phenotype.
AB  - Neurofibromatosis type I (NF1) is a hereditary tumor and developmental disorder
      whose defective gene was cloned previously. The protein product of the NF1 gene,
      neurofibromin, contains a domain that shows significant sequence homology to the
      known catalytic domains of mammalian Ras GTPase-activating proteins (GAP) and the
      yeast IRA1 and IRA2 proteins. This homologous region of neurofibromin has been
      shown to exhibit GAP activity toward Ras proteins. Malignant schwannoma cell
      lines from NF1 patients contain normal levels of GAP and nonmutated Ras proteins
      but barely detectable levels of neurofibromin, based on genetic mutations in the
      NF1 gene. Because these cells contain constitutively activated Ras.GTP, it has
      been proposed that neurofibromin may be the sole negative regulator of Ras in
      these cells. Overall, these results have implied an important role of the Ras
      signaling pathway in NF1 malignant schwannomas. Recently, several laboratories
      have developed small molecule inhibitors of Ras function that inhibit the enzyme
      farnesyltransferase (FT). FT-mediated post-translational farnesylation of Ras
      proteins is absolutely necessary for Ras function since this modification is
      required for the anchoring of Ras proteins to the plasma cell membrane. Although
      previous studies have shown that FT inhibitors can block the growth of tumor
      cells carrying mutant Ras proteins, it remained unclear how this class of
      inhibitors would affect tumor cells such as in NF1, whose malignant growth
      appears to be mediated by up-regulation of wild-type Ras activity. Thus, in the
      current study, we investigated whether BMS-186511, a bisubstrate analogue
      inhibitor of FT, would inhibit the malignant growth properties of a cell line
      established from malignant schwannoma of an NF1 patient. Our results indicate
      that the malignant growth properties of ST88-14 cells, the most malignant cell
      line among several well-characterized NF1 cells, are inhibited by BMS-186511 in a
      concentration-dependent manner. Following treatment with BMS-186511, ST88-14
      cells became flat, nonrefractile, were contact-inhibited, and lost their ability
      to grow in soft agar. In the drug-exposed cells, Ras proteins were prevented from
      FT-mediated membrane association. BMS-186511 was found to specifically inhibit
      FT, but not geranylgeranyltransferase I, a closely related enzyme. Thus, it is
      conceivable that FT inhibitors may ultimately become the first generation of
      drugs against the malignant phenotype in NF1 based on rational insights into the
      mechanism of action of neurofibromin.

PMID- 7627967
TI  - A human monoclonal antimelanoma single-chain Fv antibody derived from tumor
      infiltrating lymphocytes.
AB  - With the development of recombinant DNA technology, it has become feasible to
      clone, construct, and express fully human immunoglobulin molecules. Here we
      report a novel methodology to make human antitumor single-chain Fv (scFv)
      antibodies from tumor-infiltrating B lymphocytes. We isolated and expanded tumor
      infiltrating B lymphocytes from melanomas in the presence of Epstein-Barr virus.
      The transformed B cells secreting tumor-specific antibodies were identified and
      cloned by limiting dilution. From one B cell clone with specific melanoma
      reactivity, we captured the immunoglobulin variable region genes VH and Vk by
      PCR, sequenced the genes, and linked them together by PCR assembly with the use
      of a (Gly4Ser)3 linker. The scFv gene was then cloned into the pET21d vector and
      expressed. The obtained scFv protein with a M(r), of 29,000 was purified and
      biotinylated for further characterization. The scFv demonstrated specific tumor
      reactivity to 21 of 24 different melanoma cell lines and not to 14 nonmelanoma
      tumor cell lines, such as breast, ovarian, and colon cancer cells lines; normal
      human melanocytes as well as normal human leukocytes. These results were obtained
      in (a) a tumor cell ELISA, (b) fixed cell immunofluorescence, and (c) live cell
      flow cytometry. The immunoprecipitation results indicated that a protein antigen
      of M(r) 45,000 was recognized by the scFv. Since we reported previously that
      about 70% of human tumors of different histological types contain tumor
      infiltrating B lymphocytes producing specific antitumor antibodies, this approach
      offers a rapid, effective method by combining in vitro B-cell expansion and PCR
      gene cloning to elucidate the repertoire of the human antitumor immune response
      and to make human monoclonal antitumor antibody molecules.

PMID- 7627968
TI  - Production of interleukin 8 in adult T-cell leukemia cells: possible
      transactivation of the interleukin 8 gene by human T-cell leukemia virus type I
      tax.
AB  - Interleukin 8 (IL-8) mRNA was detected in peripheral leukemic cells obtained from
      adult T-cell leukemia patients, as well as in cultured human T-cell leukemia
      virus type I (HTLV-I)-infected T-cell lines (HUT-102, MT-1, SALT-3, and SKT-1B).
      With the use of ELISA, IL-8 protein was also detected in the culture medium of
      these cells and in the extracellular fluids of patients. Furthermore, we
      demonstrated that the HTLV-I-derived transactivator protein, tax, could stimulate
      endogenous IL-8 gene expression in an uninfected T-cell line (Jurkat) and in a
      rheumatoid synovial cell line (E-11). Induction of IL-8 by tax at protein level
      was also demonstrated in transfected cells. We found that the IL-8 NF-kappa B
      binding site specifically formed a complex with NF-kappa B-containing nuclear
      extracts from HTLV-I-infected T-cell lines and freshly isolated leukemic cells
      from adult T-cell leukemia patients. Finally, transfection of HTLV-I tax into
      Jurkat cells resulted in induction of specific binding of nuclear extracts to the
      NF-kappa B sequence. These results suggest that the HTLV-I tax gene may
      transactivate the IL-8 gene through the kappa B site in HTLV-I-infected cells and
      that constitutive expression of the IL-8 gene may play a role in HTLV-I
      associated pathogenesis.

PMID- 7627969
TI  - p53 mutations in nonmelanoma skin cancer of the head and neck: molecular evidence
      for field cancerization.
AB  - Multiple and distinct p53 mutations were detected by DNA sequence analysis in
      tumor and adjacent nonmalignant skin samples from eight patients with nonmelanoma
      skin cancer of the head and neck, providing unambiguous evidence for field
      cancerization. The mutations consisted of C-->T transitions at dipyrimidine
      sequences (30% of all single base substitutions), T-->C transitions (47%), and G-
      >T transversions (12%), suggesting that other carcinogens may act along with UV
      radiation in the development of nonmelanoma skin cancer. Patient interviews
      revealed that, in addition to substantial exposure to solar UV radiation, most
      had a history of smoking and were exposed to carcinogens from industrial or
      agricultural sources. These data show that extensive molecular epidemiological
      investigations are necessary to elucidate risk factors associated with the
      disease in localities where patients often report substantial exposure to
      environmental carcinogens.

PMID- 7627970
TI  - Aberrant expression of the myeloid zinc finger gene, MZF-1, is oncogenic.
AB  - The zinc finger gene MZF-1 is preferentially expressed in primitive hematopoietic
      cells and plays an important role in regulating myelopoiesis. Regulators of
      development are potential targets for neoplastic transformation. This study
      investigated whether unregulated expression of MZF-1 could function as an
      oncogene. Retroviral transduction and subsequent overexpression of MZF-1 resulted
      in loss of contact inhibition, loss of substrate dependence, and more rapid cell
      cycling in NIH 3T3 cells. The MZF-1-transformed 3T3 cells formed aggressive
      tumors in athymic mice. Disruption of the tight lineage- and stage-specific
      regulation of MZF-1 can result in neoplastic transformation of embryonic
      fibroblasts. Therefore, MZF-1 represents a novel oncogene.

PMID- 7627971
TI  - Anemia-inducing substance from plasma of patients with advanced malignant
      neoplasms.
AB  - Patients with advanced malignant neoplasms develop anemia and immunosuppression.
      During an attempt to identify the causes, we have found that plasma from such
      patients makes RBCs more fragile in hypotonic buffer, according to results
      obtained with a coil planet centrifuge. Plasma from these patients suppresses
      mitogen-stimulated lymphocyte proliferation. In this study, we identified the
      substance with these effects as a protein. During two-dimensional gel
      electrophoresis, two isomers with M(r) 50,000 and slightly different isoelectric
      points near 6.0 were found. Cell fractionation showed that these proteins were in
      both the cytosol and the nuclear fraction of cells in neoplasms. Another protein
      with the same antigenicity and a M(r) 100,000 found in the nuclear fraction of
      cells in neoplasms.

PMID- 7627972
TI  - Inhibition of organ invasion by the matrix metalloproteinase inhibitor batimastat
      (BB-94) in two human colon carcinoma metastasis models.
AB  - The effect of the matrix metalloproteinase inhibitor batimastat was evaluated in
      two human colorectal cancer metastasis models involving: (a) the liver-invasive
      tumor C170HM2 and (b) the lung-invasive tumor AP5LV, both of which have been
      shown to express the M(r) 72,000 type IV collagenase. Batimastat at
      concentrations between 0.01 and 3.0 micrograms/ml had no direct cytotoxic effects
      on the in vitro growth of the cell lines. In the liver-invasive tumor model,
      batimastat administered i.p. from day 10 to termination of the therapy (day 39)
      at 40 mg/kg reduced both the mean number of liver tumors (35% of vehicle-treated
      control; P < 0.05) and the cross-sectional area of the tumors (43% of vehicle
      treated control; P < 0.05). In the lung-invasive tumor model, batimastat
      administered daily (40 mg/kg i.p.) significantly reduced tumor weight within the
      lung (72% of vehicle-treated control; P < 0.05) but did not significantly affect
      nodule number. In the latter model, in which the take rate was unaffected, tumor
      cells were introduced into the lateral tail vein, and lung localization may have
      been a physical phenomenon not involving invasion. In the former model, tumor
      cells were introduced directly into the peritoneal cavity, and from there the
      cells adhered to and invaded the liver capsule. Because the take rate is
      significantly reduced, it may be that the matrix metalloproteinases are involved
      in this process. Batimastat may be a therapeutic modality for the treatment of
      colorectal cancer metastasis.

PMID- 7627973
TI  - Expression of insulin-like growth factor II in spontaneously immortalized rat
      mesothelial and spontaneous mesothelioma cells: a potential autocrine role of
      insulin-like growth factor II.
AB  - Insulin-like growth factors (IGFs) are polypeptides that play an important role
      in cellular proliferation and differentiation. The present study examines the
      role of IGFs in the growth of mesothelial cells. Cell lines derived from normal
      rat mesothelium as well as lines derived from spontaneous rat mesotheliomas were
      found to express RNA transcripts for IGF-II. In contrast, cell lines derived from
      asbestos-induced rat mesotheliomas did not express this growth factor. All cell
      lines expressed receptors for IGF-I and IGF-II, as well as insulin receptors.
      Coexpression of IGF-II and its cognate receptor suggested that IGF-II was acting
      as an autocrine growth factor in the spontaneously immortalized cells and the
      cells derived from the spontaneous tumors. The biological activity of IGF-II
      secreted by the cell lines into conditioned medium could be neutralized using an
      IGF-II-specific antibody. Growth was inhibited in a dose-dependent manner; at the
      highest antibody concentration used (100 micrograms anti-IGF-II/ml), cell growth
      was decreased to 47% of control values. This inhibition was partially reversible
      by treatment of the cultures with IGF-II (91% of the control). These data suggest
      that IGF-II expression may be involved in the spontaneous alteration of rat
      mesothelial cells and may function as an autocrine or paracrine growth factor to
      modulate the growth of these cells in vitro and in vivo. Ubiquitous expression of
      IGF-II by cells that have not been exposed to asbestos and the lack of IGF-II
      expression by asbestos-transformed cells suggest that the mechanisms of changes
      in growth factor expression differ in mesothelial cells transformed by different
      pathways.

PMID- 7627974
TI  - Introduction of an activated N-ras oncogene alters the growth characteristics of
      the interleukin 6-dependent myeloma cell line ANBL6.
AB  - Multiple myeloma (MM) is a late-stage B-cell cancer with an unknown etiology.
      Activating mutations of the N-ras and K-ras oncogenes occur with a high frequency
      in myeloma and, therefore, may play a role in the pathogenesis of the disease. To
      study the role of N-ras-activating mutations in the regulation of myeloma tumor
      growth, we introduced a constitutively active N-ras cDNA containing a glutamine
      to arginine (CAA-CGA) amino acid substitution at codon 61 into the interleukin 6
      (IL-6)-dependent myeloma cell line ANBL6. Expression of the mutant N-ras cDNA
      resulted in significant IL-6-independent growth, as well as augmentation of
      growth at suboptimal concentrations of IL-6. The IL-6-independent growth pattern
      was not the result of activation of autocrine IL-6 production in the mutant N-ras
      expressing population because neutralizing antibodies to the IL-6 receptor and to
      IL-6 had no effect on the rate of DNA synthesis in the absence of IL-6.
      Furthermore, mutant N-ras expression decreased the percentage of cells undergoing
      apoptosis in the absence of IL-6. These data suggest that activating mutations of
      the ras oncogenes may result in growth factor independence accompanied by a
      suppression of apoptosis in MM. Therefore, the use of therapies designed to block
      IL-6 action in MM may have less of an impact on tumors bearing activated ras
      mutations.

PMID- 7627975
TI  - Fucosyltransferase and alpha-L-fucosidase activities and fucose levels in normal
      and malignant endometrial tissue.
AB  - Previous immuno- and lectin-histochemical studies using mAbs and Ulex europaeus
      lectin I, which recognize various fucose-containing blood group antigens, have
      shown an increased expression of Lewis and H blood group antigens in endometrial
      carcinoma. We investigated the biochemical basis of aberrant fucose-containing
      antigen expression by comparing the activity of fucosyltransferases (FTase) and
      alpha-L-fucosidase in tissue biopsies from normal (n = 18) and malignant (n = 20)
      endometrium. Alteration of FTase activity in tumor tissue homogenates was
      evaluated by using a panel of FTase substrates including N-acetyllactosamine
      (type 2), lacto-N-biose I (type 1), and phenyl-beta-D-galactoside. Based on
      histological subtyping, the endometrioid group (n = 14) showed a significant (P <
      0.05) increase in tumor FTase activity with all three substrates, while no
      significant increase was detected for the papillary serous group (n = 4). Matched
      pair analysis of normal and tumor tissue from a subgroup (n = 5) of the patients
      with increased tumor enzyme activity also showed higher FTase activity (P < 0.05)
      in the tumor tissue when the type 1 substrate was used. Regression analysis
      showed a correlation between the FTase activities acting on type 2 or type 1
      substrates (r = 0.821 and r = 0.722, respectively) and the endogenous fucose
      levels in tumor homogenates. Spectrophotometric analysis of alpha-L-fucosidase
      activity using p-nitrophenyl-alpha-L-fucoside revealed a higher activity in tumor
      homogenates than in normal homogenates (P < 0.05) and, therefore, could not
      account for the enhanced expression of fucose-containing antigens. The current
      study suggests that aberrant expression of fucose-containing antigens, such as
      the H and the Lewis blood-group antigens, in endometrial carcinoma is
      consequential to the change in FTase rather than in alpha-L-fucosidase activity.
      In addition, the investigation suggests that different glycosylation mechanisms
      are operative in different subtypes of endometrial cancer.

PMID- 7627976
TI  - Association of sialyl-Lewis(a) and sialyl-Lewis(x) with MUC-1 apomucin ina
      pancreatic cancer cell line.
AB  - We have shown previously that the mucins of the human pancreatic cancer cell
      line, SW1990, have both sialyl-Lewis(a) and sialyl-Lewis(x) carbohydrate ligands
      that are implicated in tumor cell metastasis. In the present study, we undertook
      to identify the protein core of these mucins. SW1990 mucins that carry sialyl
      Lewis(a) and sialyl-Lewis(x) bound to the MUC1 peptide-specific mAb 139H2.
      Removal of most of the sialic acids from SW1990 mucins by neuraminidase greatly
      enhanced binding of two other MUC1 peptide specific antibodies, HMFG-2 and SM-3.
      After removal of sialic acids, most of the mucins rich in sialyl-Lewis(a) and
      sialyl-Lewis(x) oligosaccharides no longer bound to a DEAE-cellulose column at pH
      8.0. These results indicate that at least part of the sialyl-Lewis(a) and sialyl
      Lewis(x) in SW1990 cells is associated with the MUC1 polypeptide. Moreover,
      sialic acids play an important role in determining the net negative charge of
      sialyl-Lewis(a) and sialyl-Lewis(x) rich mucins and in obscuring MUC1 peptide
      regions.

PMID- 7627977
TI  - Protection by grafts of embryonal rat tissues (teratomas) against induction and
      transplantation of malignant tumors.
AB  - Clinical observations and experimental studies have shown that pregnancy may have
      inhibitory effects on tumor growth rather than invariably aggravate neoplastic
      disease as believed previously. It has been suggested that circulating factors of
      maternal or fetal origin may protect against tumor growth during pregnancy. The
      previously created experimental model of teratomas provides the means of having
      an adult animal bearing a permanent graft of embryonal tissues. To investigate
      the potential effects of embryonal factors on the growth of malignant neoplasms,
      rats carrying grafts of embryonal tissues were subjected to the induction or
      transplantation of carcinomas and lymphomas. Finely minced embryo tissues or cell
      suspensions injected in homologous rat recipients formed permanent benign
      teratomas composed of a variety of well differentiated tissues. One injection of
      N-methyl-N-nitrosourea, a potent carcinogen administered to all rats, induced
      fatal mammary adenocarcinoma in 50-60% of control rats but in none of the rats
      bearing a grafted teratoma. Transplantation of N-methyl-N-nitrosourea-induced
      mammary adenocarcinoma or Gross virus-induced lymphoma killed 100% of control
      rats but resulted in smaller, later appearing tumors in only 25-61% of teratoma
      bearing rats. The present experiments showed that rats bearing grafts of
      embryonal tissues in the form of teratomas were partially or totally protected
      against the induction and transplantation of malignant tumors that killed 100% of
      controls. These results suggest that the embryonal tissues are a source of tumor
      inhibitory factors, which may be a part of mechanisms controlling the growth and
      detecting the aberrations of embryonal tissues. Their identification and analysis
      may provide knowledge about embryonal growth and possibly about new substances
      with antineoplastic activity.

PMID- 7627978
TI  - Identification and characterization of an Epstein-Barr virus-specific T-cell
      response in the pathologic tissue of a patient with Hodgkin's disease.
AB  - Several lines of evidence indicate that an impairment of EBV-specific immune
      responses may contribute to the pathogenesis of Hodgkin's disease (HD). At
      present, however, it is not clear whether a defective immunity to EBV is a
      characteristic restricted to EBV-associated HD cases or a more generalized
      phenomenon, part of the inherent immune deficiency of HD patients. In this study,
      we have addressed this issue by analyzing EBV-specific responses in infiltrating
      T lymphocytes (TILs) from one HD biopsy, where the virus was confined to a small
      proportion of apparently normal lymphocytes. TIL cultures were established using
      low amounts of recombinant interleukin 2 and in the absence of specific
      stimulation, conditions that preferentially induce the proliferation of in vivo
      activated T cells. An EBV-specific cytotoxic component was revealed by the
      capacity of these TILs to lyse autologous EBV-positive lymphoblastoid cell lines
      (LCLs) obtained by spontaneous transformation from the lesion but not HLA
      mismatched LCLs and autologous phytohemagglutinin blasts. This cytotoxic activity
      closely resembled that of EBV-specific memory T cells, which may be reactivated
      from the blood lymphocytes of healthy donors by in vitro stimulation with
      autologous LCLs. The use of a panel of appropriately HLA-matched B95.8
      transformed LCLs as targets in standard 51Cr release assays revealed EBV-specific
      cytotoxic responses to be restricted mainly through the A11 and B44 HLA alleles
      with a minor HLA-A26-restricted component. Using autologous fibroblasts infected
      with recombinant vaccinia viruses expressing the EBV latent antigens, the TIL
      culture was shown to recognize latent membrane protein 2 and, to a lesser extent,
      EBV-encoded nuclear antigen 6. In addition, a strong proliferative response was
      induced by coculture of TILs with autologous but not with allogeneic LCLs or
      autologous phytohemagglutinin blasts. Six CD4-positive, EBV-specific T-cell
      clones were isolated by limiting dilution. The study of cytokine mRNA expression,
      carried out by reverse transcriptase-assisted PCR, revealed that three of these T
      cell clones expressed a Th0 phenotype, whereas 1 had a Th2 phenotype. These
      findings are consistent with the presence in this HD lesion of an ongoing immune
      response against EBV-carrying cells and suggest that the complex immune
      deficiency that characterizes HD patients probably does not include a
      generalized, constitutional defect of EBV-specific T-cell responses.

PMID- 7627979
TI  - Featuring a fellowship: Zambia.

PMID- 7627980
TI  - Reflections: on Christian nursing services.

PMID- 7627982
TI  - Research--a continuing quest for truth.

PMID- 7627981
TI  - On secular and Christian hospitals--are they different?

PMID- 7627983
TI  - Power and powerlessness in practice.

PMID- 7627984
TI  - Reflections: on a model of a Christian nurse.

PMID- 7627985
TI  - Shall we play 'doctors and nurses'? Problems in nurse-doctor relationships.

PMID- 7627986
TI  - Gel-to-sol transition of 13C-labeled (1-->3)-beta-D-glucan, 13C-SSG, assessed by
      13C nuclear magnetic resonance (13C-NMR) spectroscopy.

PMID- 7627987
TI  - Structure determination of galacto-oligosaccharides by pyridylamination and NMR
      spectroscopy.
AB  - Galacto-oligosaccharides formed from lactose by the action of some beta
      galactosidases were subjected to gel chromatography on Bio-Gel P-2, and the
      resulting oligosaccharide fractions were converted into pyridylamino (PA)
      derivatives. Each PA-oligosaccharide fraction, which consisted of several isomers
      in a given size-class, was then  subjected to HPLC on an ODS column. Twenty-one
      individual galacto-oligosaccharide components were isolated in this way. The
      structures of most of these compounds, namely six disaccharides, five
      trisaccharides, two tetrasaccharides, and a pentasaccharide, were determined by
      13C-NMR spectroscopy. The results obtained will be useful for the study of the
      activity of various galacto-oligosaccharides on the growth of Bifidobacterium
      species.

PMID- 7627988
TI  - Synthesis of a thio analogue of n-propyl kojibioside, a potential glucosidase
      inhibitor.
AB  - The disaccharide alpha-D-Glc p-(1-S-2)-beta-D-Glc p-(1-OPr) 1, a thio analogue of
      alpha-D-Glc p-(1 --> 2)-alpha-D-Glc p-(1-OPr)(n-propyl kojibioside) in which the
      inter-glycosidic oxygen atom is replaced by sulfur, has been synthesized for
      evaluation as a potential glucosidase inhibitor. Glycosylation of the 2-thiol
      glucopyranosyl acceptor 4 with the trichloroacetimidate of 2,3,4,6-tetra-O-benzyl
      alpha-D-glucopyranose 5 gave the alpha-linked disaccharide 6 stereoselectively.
      Deprotection was performed by hydrogenolysis in the presence of Pd/C to give 1 as
      the beta-n-propyl glycoside. Glycosylation of the thiol 4 with the
      trichloroacetimidate of 2,3,4,6-tetra-O-acetyl-alpha-D-glucopyranose 8 gave a
      1:2.3 mixture if the alpha and beta disaccharides (9 and 10); evidence is
      presented for the occurrence of the orthoester 11, as an intermediate in the
      formation of the beta-disaccharide.

PMID- 7627989
TI  - A new synthesis of sucrose 6'-phosphate.
AB  - Sucrose 6'-phosphate (3) is the key intermediate for sucrose (1) synthesis in
      plants [1]. It has recently become commercially available at ca. $1500/g (Sigma).
      The only chemical synthesis is that of Buchanan et al. [2]. This six-step
      procedure, while unambiguous, gives an overall yield of only ca. 6%. We describe
      here a simplified route (2 steps) with an unoptimized yield of ca. 15%. Our
      strategy was to use a phosphorylation reagent selective for primary hydroxyl
      groups and thus to avoid the necessity for blocking all of the secondary ones.
      Sowa and Ouchi [3] described a suitable system which they used very effectively
      for the synthesis of 5'-nucleotides from unprotected nucleosides. We applied this
      reagent to 2,1':4,6-di-O-isopropylidenesucrose (2) [4] in which the only
      unprotected primary hydroxyl group is that at the 6'-position (Scheme 1). The
      identity of the product was established by comparison of its rotation with the
      literature value and by the correspondence of its 1H and 13C NMR spectra with
      those of an authentic sample synthesized by Buchanan's method (Sigma) 1H
      assignments were made with the help of the assignments of du Penhoat et al. [5]
      for sucrose and the results of a one-bond H-C COSY experiment (Fig. 1). The 13C
      spectrum showed that all of the resonances were shifted downfield by ca. 0.5 ppm
      as compared with sucrose [6] except for the C-5' doublet which was shifted
      upfield by 0.5 ppm and the C-6' doublet which was shifted downfield by 2.2 ppm
      (Table 1).

PMID- 7627990
TI  - Synthesis of (3'R)-3'-deoxy-3'-C-nitromethylthymidine.

PMID- 7627991
TI  - Protective specific immunity induced by cyclophosphamide plus tumor necrosis
      factor alpha combination treatment of EL4-lymphoma-bearing C57BL/6 mice.
AB  - A combination treatment protocol initiated 12 days after tumor injection, when
      the tumor was large, by administering cyclophosphamide (CY, 150 or 250 mg/kg)
      intraperitoneally followed by intravenous tumor necrosis factor alpha (TNF alpha,
      1000 units injection) on days 13, 16, 18, 21, and 23, resulted in about 60% long
      term survival (i.e., survival for at least 60 days) in the syngeneic C57BL/6
      mouse/EL4 lymphoma model system. The establishment of a specific antitumor immune
      memory and its possible therapeutic relevance was verified by reinjecting 60-day
      survivors with EL4 cells; all 60-day survivors that had received the combination
      treatments rejected the implants and survived for a further 60 days. Thymic
      cellularity was reduced during treatment and its recovery appeared to correlate
      with long-term survival and immunity. Thymocytes from mice treated with the
      combination were found to express significant levels of specific anti-EL4
      cytolytic activity following a 4-day stimulation culture with X-irradiated EL4
      cells and low concentrations of interleukin-2. This response could not be
      generated with thymocytes from naive animals. In each case the effect seen with
      the combination of a moderate CY dose (150 mg/kg) with TNF alpha was better than
      that seen with either dose of CY alone and equal to or better than that seen with
      the higher dose of CY combined with TNF alpha. These results indicate that
      treatment with a single moderate dose of CY in combination with TNF alpha is
      effective against a large, established tumor in this murine model. Furthermore,
      all the long-term survivors induced by this treatment developed protective
      immunity against reimplanted tumor and demonstrated a long-term specific immune
      memory in the thymus.

PMID- 7627992
TI  - Suppression of cytotoxic T lymphocyte activity by gamma/delta T cells in tumor
      bearing mice.
AB  - Spleen cells derived from tumor-bearing mice prove useful for the elucidation of
      the mechanism determining how tumor cells evade cytotoxic T lymphocytes (CTL) in
      tumor-bearing hosts. Our data indicate that inactive CTL or precursor CTL
      specific for tumor antigens are present among lymphocytes of tumor-bearing mice.
      However, their activity is inhibited by a soluble factor produced by other cells
      present in the same source. Inhibition of the cytolytic reaction was also
      detected in the culture supernatant of spleen cells obtained from normal mice,
      precultured in the presence of tumor cell culture supernatant and interleukin-2
      (IL-2). Cell-depletion and cell-purification studies let us conclude that cells
      that produced the CTL-inhibitory factor (CTL-IF) were gamma/delta T cells. The
      gamma/delta T cells that were activated in vivo in tumor bearers were able to
      produce CTL-IF after isolation and in vitro culture. Maximum activation of
      gamma/delta T cells was achieved by antigenic stimulation and by suppression of
      cells that interfered with the activation of gamma/delta T cells. CTL-IF, which
      was assayed by use of CTL clones, did not show antigen specificity. Inhibition
      depended on a relatively heat- and acid-stable, but alkali-labile molecule with a
      molecular mass of less than 10 kDa. The latter characteristics imply that CTL-IF
      does not resemble any of the known lymphokines produced by gamma/delta T cells.
      These observations emphasize the crucial role of the gamma/delta T cells in the
      escape of tumor cells from the attack of tumor-specific CTL.

PMID- 7627993
TI  - Granulocyte/macrophage-colony-stimulating factor augments the induction of
      antibodies, especially anti-idiotypic antibodies, to therapeutic monoclonal
      antibodies.
AB  - A group of 86 patients with advanced colorectal carcinoma were treated with the
      mouse (m) (IgG2A) or chimeric (c) monoclonal antibody (mAb) 17-1A. Prior to
      therapy, no patient had detectable levels of antibodies to mAb17-1A. All mmAb17
      1A-treated patients (n = 76) developed antibodies against both idiotypic and
      isotypic determinants. Addition of granulocyte/macrophage-colony-stimulating
      factor (GM-CSF) to mmAb17-1A significantly enhanced the induction of anti
      idiotypic (ab2) as well as anti-isotypic antibodies. Of the mmAb17-1A-treated
      patients, 16 developed type I allergic reactions. These patients had
      significantly higher concentrations of anti-(mouse Ig) antibodies than patients
      without type I reactions. Of these 16 patients, 5 had received mmAb17-1A alone;
      they constituted 9% of this group (5/56). The remaining 11 patients had been
      given mmAb17-1A together with GM-CSF, and represented 55% of this treatment group
      (11/20). The difference was statistically significant (P < 0.001). Of 10
      patients, 9 (90%) treated with cmAb17-1A and GM-CSF developed ab2. The ab2
      concentration in this patient group was significantly lower compared to those
      treated with mmAb-17A. Anti-(mouse Ig) antibodies caused clinical symptoms
      requiring therapeutic intervention in fewer than 10% of the patients treated with
      mmAb17-1A alone. With the addition of GM-CSF, the antibody concentration as well
      as the frequency of allergic side-effects calling for medical action increased
      significantly. Significantly more patients with a high ab2 concentration (at
      least 15 micrograms/ml) 1 month after completion of mAb therapy responded to mAb
      treatment as compared to those with a low ab2 concentration (P < 0.05). Moreover,
      patients with a high ab2 concentration (at least 15 micrograms/ml) had a median
      survival time of 15 months while those with a lower concentration survived for a
      median time of 9 months (P = 0.01).

PMID- 7627994
TI  - Activation of human lymphocytes by a monoclonal antibody to B lymphoblastoid
      cells; molecular mass and distribution of binding protein.
AB  - A novel monoclonal antibody (BAT) to the B-lymphoblastoid cell line activates
      murine lymphocytes and exhibits a striking antitumor activity in mice. In order
      to evaluate the potential use of this antibody against human cancer, we have
      investigated its immuno-stimulatory properties on human peripheral blood
      lymphocytes (PBL). Our findings demonstrate that BAT mAb induces proliferation
      and cytotoxicity in human PBL against natural-killer-cell-sensitive and natural
      killer-cell-resistant tumor cell lines. Interleukin-2 at a low concentration
      synergizes with BAT mAb in eliciting these effects. BAT mAb binds to human
      peripheral T cells as revealed by a double-labelling technique using anti-CD3 and
      BAT mAb. The molecular mass of the antigen recognized by BAT mAb was 48-50 kDa
      under reducing and non-reducing conditions. This study provides a basis for
      future experiments to evaluate the use of BAT mAb in the immunotherapy of cancer.

PMID- 7627995
TI  - A rat monoclonal anti-(human CD2) and L-leucine methyl ester impacts on
      human/SCID mouse graft and B lymphoproliferative syndrome.
AB  - The transfer of human peripheral blood mononuclear cells (hu-PBMC) from adult
      Epstein-Barr-virus(EBV)-seropositive donors in SCID (severe combined
      immunodeficiency) mice frequently leads to the development of a human B
      lymphoproliferative syndrome (hu-BLPS). Therefore, as 90% of adult potential
      donors are EBV-seropositive, efforts have to be made to avoid the occurrence of
      this B lymphoproliferative disorder. McCune et al. [Science 241:1632 (1988)] used
      human fetal organs for a human SCID graft. This system does not give rise to hu
      BLPS but human fetal organs are much less available than peripheral blood
      leucocytes. The experiments reported in this paper show how crucial is the
      presence of functional T lymphocytes for a graft to take and for development of
      hu-BLPS in hu-PBMC-reconstituted SCID mice, since inhibition of T lymphocyte by a
      rat anti-(human CD2) monoclonal antibody (LO-CD2a) during the first 10 days of
      the graft prevents successful engraftment of human normal lymphocytes as well as
      hu-BLPS in SCID mice. The transfer of B cells alone or B cells plus monocytes in
      SCID mice does not permit either long-term engraftment or development of hu-BLPS.
      We also demonstrate that hu-PBMC treated with L-leucine methyl ester are less
      susceptible to the development of hu-BLPS after engraftment in SCID mice than are
      untreated hu-PBMC. The mechanism of action of L-leucine methyl ester on these
      cells is discussed.

PMID- 7627996
TI  - Generation of cytotoxic effector cells against human melanoma.
AB  - Metastatic or tumor-draining lymph nodes from six of nine melanoma patients
      undergoing lymph node dissection for metastatic melanoma generated cytotoxic T
      cells against autologous melanoma when these lymph node cells were treated by in
      vitro sensitization and recombinant interleukin-2 (IL-2). During the initial
      lymphocyte culture (2-6 weeks), cross-reactivity with autologous tumor cells,
      K562 and Daudi cells was usually noted. Cold-target inhibition assay with K562
      and Daudi showed K562/Daudi-associated antigens on melanoma cells. During the
      later phase of lymphocyte culture with repeated in vitro sensitization (over 6-10
      weeks), cytotoxicity was noted against autologous and allogeneic melanoma cells
      but not against K562. Daudi cells or autologous fibroblasts. Repeated in vitro
      sensitization resulted in the selection of specific cytotoxic lymphocytes against
      melanoma. Cold-target inhibition assay with autologous and allogeneic melanoma
      cells revealed shared and individual antigens. Using blocking monoclonal
      antibodies, MHC-restricted killing was noted in the autologous system. Further,
      both the autologous and allogeneic systems could be mediated through adhesion
      molecules such as ICAM-1 and LFA-3 on melanoma cells and LFA-1 on T cells. This
      study suggests that a constellation of cytotoxic effector cells and melanoma
      associated antigens may be pivotal in tumor killing. Thus, future adoptive
      immunotherapy should modulate and enhance this complex interaction.

PMID- 7627997
TI  - Paediatric treatment costs and the HIV epidemic.
AB  - As the AIDS epidemic puts additional strains on the already overburdened health
      care systems in sub-Saharan Africa, it becomes more important to estimate the
      cost of the epidemic in terms of health personnel and drug treatments. A
      retrospective review of 250 randomly selected paediatric admissions to a referral
      hospital in Malawi was undertaken. Groupings of "possible/probable AIDS" and
      "probably not AIDS" were used in a comparative analysis of treatment costs.
      Estimated costs of treatments were significantly lower than those calculated in a
      study from Zimbabwe using different methodology. Meningitis was the most
      expensive condition to treat and accounted for a greater percentage of overall
      cost than either acute respiratory infection, diarrhoeal disease or measles.

PMID- 7627999
TI  - Impact of primary health care on child morbidity and mortality in rural Ghana:
      the Gomoa experience [corrected].
AB  - The impact of a combination of PHC intervention activities on child survival,
      growth, morbidity and mortality was assessed in three selected rural communities
      (Gomoa Fetteh, Gomoa Onyadze/Otsew Jukwa and Gomoa Mprumem) in the Central Region
      of Ghana from 1987 to 1990. EPI, provision of basic essential drugs and supplies
      for the treatment of common childhood diseases, treatment of the sick child,
      growth monitoring, health education, provision of antenatal services, family
      planning, training and supervision of Community Health Workers, disease
      surveillance and special studies were the major PHC strategies used to improve
      the health of the child and the pregnant woman in the three communities. These
      activities in their totality have had significant impact on morbidity and
      mortality in children under five and on maternal mortality in children under five
      and on maternal mortality over the study period 1987 to 1990. Although malaria,
      acute respiratory infections and diarrhoea diseases continue to be major causes
      of childhood morbidity, deaths due to these diseases have dramatically declined.
      Measles and other vaccine preventable diseases no longer contribute significantly
      to childhood morbidity and mortality. Infant and under five mortality have been
      reduced from 114.6/1000 and 155.6/1000 live births to 40.8/1000 and 61.2/1000
      live births respectively. The crude birth rates however, remain almost the same
      over the five year period (43 to 48/1000 pop.) but crude death rates have
      declined (11 to 12.4/1000 pop.).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7627998
TI  - Is the protection afforded measles vaccinees the same in children of all age
      groups?
AB  - A prospective study was carried out in the City of Gweru in 1988 to examine the
      relationship between age and protection afforded measles vaccinees by the measles
      vaccine. The age group 10 months to nine years accounted for 240 cases or 87 pc
      of the 276 measles cases reported in 1988. The disease had shifted towards older
      age groups with children aged 10 to 59 months accounting for 105 cases or 43.7 pc
      and those aged five to nine years accounting for 135 cases or 56.3 pc of the 240
      measles cases reported in the age group 10 months to nine years. In all the sub
      age groups of the age group 10 months to nine years i.e. 10 to 23 months, 24 to
      35 months, 36 to 47 months etc. the proportion of vaccinated cases was more than
      that of unvaccinated cases and the incidence rates in the unvaccinated population
      were all higher than in the vaccinated population. A correlation of age and
      relative risk (relative risk was calculated for each sub-age group) showed a
      significant negative trend (correlation coefficient = -0.79; p = 0.012).

PMID- 7628000
TI  - Body fat distribution and other anthropometric blood pressure correlates in a
      Nigerian urban elderly population.
AB  - Blood pressure (BP) has been reported to be more consistently correlated with
      body mass index (BMI) than with waist-hip ratio (WHR) in Blacks. We present the
      correlates of BP in a systematic sample of 152 (65.7 pc response rate) elderly
      urban Nigerians, with a mean age of 72.7 yrs. +/- 12.1 for males and 73.2 yrs, +/
      11.9 for females. There were 12.3 pc and 22.3 pc obesity rates in the males and
      females respectively, with an equivalent mean BMI of 22.8 kg/m2 and 23.4 kg/m2
      and WHR of 0.97 and 0.94. Systolic blood pressure (SBP) and diastolic blood
      pressure (DBP) correlated with BMI, r = 0.26; p < 0.01 and r = 0.42; p < 0.001,
      only in females. WHR did not correlate with BP in either sex, but waist and hip
      measurements correlated significantly with BP in both sexes. The most important
      predictor of BP is BMI for females and waist measurement for men. Although
      smoking and alcohol were not related to BP in either sex, the data suggests that
      alcohol enhanced, while tobacco inhibited weight gain significantly in males, who
      on the whole indulged more than the females. Fasting or two hour whole blood
      glucose were not related to BP. The findings are in support of the adverse
      effects of weight on BP in the elderly. There is need to study attitudes to adult
      weight gain as expressed in body shape, and to use the findings in the
      development of weight control programmes as part of blood pressure control in the
      elderly.

PMID- 7628001
TI  - Sexual ambiguity and malformation in Zambia: challenges in surgical management.
AB  - This article addresses the complexity in diagnosis, gender assignment and
      management in patients with sexual ambiguity and malformed sexual organs. Between
      1984 and 1993, nine children and 10 adult patients with this ailment were treated
      in the University Teaching Hospital, Lusaka, Zambia. All children had
      clitorovaginoplasty and adults had different surgical procedures such as
      feminisation and masculinisation operations. Methods, means and the manner in
      which we manage these patients in the midst of a scarcity of expert manpower and
      sophisticated equipment are discussed. Need for a specialised clinic for better
      management, teaching and research of this unfortunate and highly sensitive
      congenital defect has been emphasised.

PMID- 7628002
TI  - A further case of Bardet-Biedl syndrome.
AB  - Bardet-Biedl syndrome in a 10 year old boy from Botswana is described. The
      patient presented with retinitis pigmentosa, polydactyly, mental retardation,
      obesity and hypogenitalism. The patient has a twin brother who has the same
      clinical signs. This is the second time this condition has been described in the
      African literature and the first time reported in Black twins.

PMID- 7628003
TI  - Ventricular tachycardia in a patient with lymphocytic (non Hodgkin's) lymphoma.
AB  - A 19 year old student was admitted with generalised lymphadenopathy, paraplegia,
      double incontinence and weight loss in our hospital (Abuth Zaria). A histological
      diagnosis of lymphocytic (non-Hodgkin's) lymphoma was made on lymph node biopsy.
      Before treatment could be started the patient developed increasing difficulty in
      breathing. He was transferred to our ICU where he was noted to have developed no
      sustained VT. Subsequent repeated episodes did not respond to resuscitative
      measures (i.v. lignocaine 100 mg for five minutes, oxygen and assisted
      respiration). The patient died.

PMID- 7628004
TI  - Septicaemia associated with neonatal tetanus.

PMID- 7628005
TI  - A second signal recognition event required for translocation into the endoplasmic
      reticulum.
AB  - As summarized in this minireview, two different signal recognition events, one
      involving SRP and the other involving proteoliposomes containing the Sec61p
      complex, have been identified. In cotranslational protein transport, it seems
      that both recognition events are required for efficient translocation of the
      protein into the lumen of the ER. The requirement for SRP can, under certain
      experimental conditions, be circumvented by depletion of NAC, a heterodimeric
      complex that can block the tight association of nascent chain-ribosome complexes
      to the Sec61p complex in the ER membrane. In posttranslational protein transport,
      the Sec61p complex contains additional protein subunits that are required for
      function. It should be noted that, in all the experiments performed in which the
      role of SRP in cotranslational protein translocation is circumvented (Jungnickel
      and Rapoport, 1995; Lauring et al., 1995a, 1995b), stable translocation
      intermediates are allowed many minutes to establish productive interactions with
      the membrane. In contrast, during conditions in which the nascent chain can
      elongate (e.g., in vivo), the nascent chain-ribosome complex only has a brief
      time window during which it can initiate translocation (reviewed by Walter and
      Johnson, 1994). It is possible that, under these conditions, productive
      translocation even in the absence of NAC would require SRP. The isolation of NAC
      deficient extracts that support protein synthesis will allow a test of this
      possibility. Finally, the role that lipids themselves may play in protein
      transport should not be ignored. Gierasch and coworkers (Hoyt and Gierasch, 1991,
      and references therein) have shown that bacterial signal peptides have an
      intrinsic ability to interact with lipid and that the relative ability of a
      mutant signal sequence to interact with lipid correlates with its function as a
      signal sequence in vivo. Thus, the signal sequence-discriminatory role defined by
      Jungnickel and Rapoport (1995) may in fact be played by lipid, with the Sec61p
      complex playing a necessary but nondiscriminatory role in the process. In this
      light, it is interesting that Martoglio et al. (1995) recently demonstrated that
      the signal sequence of preprolactin could be cross-linked to phospholipid.
      Analysis of the cross-linking efficiency of the signal sequence to phospholipid
      at different nascent chain lengths and with mutant signal sequences will help
      define the role that phospholipid plays in the process.

PMID- 7628006
TI  - A perfect vulva every time: gradients and signaling cascades in C. elegans.

PMID- 7628007
TI  - The enigma of HIV infection.

PMID- 7628008
TI  - Can the immune response control HIV infection?

PMID- 7628009
TI  - Viral latency in HIV disease.

PMID- 7628010
TI  - HIV accessory proteins: leading roles for the supporting cast.

PMID- 7628011
TI  - Crystal structure of the site-specific recombinase gamma delta resolvase
      complexed with a 34 bp cleavage site.
AB  - The structure of gamma delta resolvase complexed with a 34 bp substrate DNA has
      been determined at 3.0 A resolution. The DNA is sharply bent by 60 degrees toward
      the major groove and away from the resolvase catalytic domains at the
      recombination crossover point. The C-terminal one third of resolvase, which was
      disordered in the absence of DNA, forms an arm and a 3-helix DNA-binding domain
      on the opposite side of the DNA from the N-terminal domain. The arms wrap around
      the minor groove of the central 16 bp, and the DNA-binding domains interact with
      the major grooves near the outer boundaries of the binding site. The resolvase
      dimer is asymmetric, particularly in the arm region, implying a conformational
      adaptability that may be important for resolvase binding to different DNA sites
      in the synaptosome. It also raises the possibility of a sequential single-strand
      cleavage mechanism.

PMID- 7628012
TI  - Structure of the bacteriophage Mu transposase core: a common structural motif for
      DNA transposition and retroviral integration.
AB  - The crystal structure of the core domain of bacteriophage Mu transposase, MuA,
      has been determined at 2.4 A resolution. The first of two subdomains contains the
      active site and, despite very limited sequence homology, exhibits a striking
      similarity to the core domain of HIV-1 integrase, which carries out a similar set
      of biochemical reactions. It also exhibits more limited similarity to other
      nucleases, RNase H and RuvC. The second, a beta barrel, connects to the first
      subdomain through several contacts. Three independent determinations of the
      monomer structure from two crystal forms all show the active site held in a
      similar, apparently inactive configuration. The enzymatic activity of MuA is
      known to be activated by formation of a DNA-bound tetramer of the protein. We
      propose that the connections between the two subdomains may be involved in the
      cross-talk between the active site and the other domains of the transposase that
      controls the activity of the protein.

PMID- 7628013
TI  - Protein facilitation of group I intron splicing by assembly of the catalytic core
      and the 5' splice site domain.
AB  - The yeast mitochondrial group I intron b15 undergoes self-splicing at high Mg2+
      concentrations, but requires the splicing factor CBP2 for reaction under
      physiological conditions. Chemical accessibility and UV cross-linking experiments
      now reveal that self-processing is slow because functional elements are not
      properly positioned in an active tertiary structure. Folding energy provided by
      CBP2 drives assembly of two RNA domains that comprise the catalytic core and
      meditates association of an approximately 100 nt 5' domain that contains the 5'
      splice site. Thus, the protein assembles RNA secondary structure elements into a
      specific three-dimensional array while the RNA provides the catalytic center. The
      division of labor between RNA and protein illustrated by this simple system
      reveals principles applicable to complex ribonucleoprotein assemblies such as the
      spliceosome and ribosome.

PMID- 7628014
TI  - The carbonic anhydrase domain of receptor tyrosine phosphatase beta is a
      functional ligand for the axonal cell recognition molecule contactin.
AB  - Receptor-type protein tyrosine phosphatase beta (RPTP beta) is expressed in the
      developing nervous system and contains a carbonic anhydrase (CAH) domain as well
      as a fibronectin type III repeat in its extracellular domain. Fusion proteins
      containing these domains were used to search for ligands of RPTP beta. The CAH
      domain bound specifically to a 140 kDa protein expressed on the surface of
      neuronal cells. Expression cloning in COS7 cells revealed that this protein is
      contactin, a GPI membrane-anchored neuronal cell recognition molecule. The CAH
      domain of RPTP beta induced cell adhesion and neurite growth of primary tectal
      neurons, and differentiation of neuroblastoma cells. These responses were blocked
      by antibodies against contactin, demonstrating that contactin is a neuronal
      receptor for RPTP beta. These experiments show that an individual domain of RPTP
      beta acts as a functional ligand for the neuronal receptor contactin. The
      interaction between contactin and RPTP beta may generate unidirectional or
      bidirectional signals during neural development.

PMID- 7628015
TI  - A posttargeting signal sequence recognition event in the endoplasmic reticulum
      membrane.
AB  - We have analyzed early phases of the cotranslational transport of the secretory
      protein preprolactin through the mammalian endoplasmic reticulum (ER) membrane.
      Following recognition of the signal sequence of the nascent polypeptide chain in
      the cytosol by the SRP, the chain is transferred into the membrane, where a
      second signal sequence recognition step takes place for which the presence in the
      lipid bilayer of the Sec61p complex is essential and sufficient. This step leads
      to a tight junction between the ribosomenascent chain complex and the Sec61p
      complex, and to the productive insertion of the nascent chain into the
      translocation site. These results show that a translocation substrate is
      subjected to two recognition events before being allowed to cross the ER
      membrane.

PMID- 7628016
TI  - A novel amino acid modification in sulfatases that is defective in multiple
      sulfatase deficiency.
AB  - Multiple sulfatase deficiency (MSD) is a lysosomal storage disorder characterized
      by a decreased activity of all known sulfatases. The deficiency of sulfatases was
      proposed to result from the lack of a co- or posttranslational modification that
      is common to all sulfatases and required for their catalytic activity. Structural
      analysis of two catalytically active sulfatases revealed that a cysteine residue
      that is predicted from the cDNA sequence and conserved among all known sulfatases
      is replaced by a 2-amino-3-oxopropionic acid residue, while in sulfatases derived
      from MSD cells, this cysteine residue is retained. It is proposed that the co- or
      posttranslational conversion of a cysteine to 2-amino-3-oxopropionic acid is
      required for generating catalytically active sulfatases and that deficiency of
      this protein modification is the cause of MSD.

PMID- 7628017
TI  - Trypanosome invasion of mammalian cells requires activation of the TGF beta
      signaling pathway.
AB  - Trypanosoma cruzi invades most nucleated mammalian cells by as yet unknown
      mechanisms. We report here that while T. cruzi attaches to epithelial cells
      lacking signaling transforming growth factor beta (TGF beta) receptor I or II,
      the adherent parasites cannot penetrate and replicate inside the mutant cells, as
      they do in parental cells. Invasion of the mutants is restored by transfection
      with the TGF beta receptor genes, as are biological responses to TGF beta.
      Similar rescue of both TGF beta antiproliferative response and T. cruzi invasion
      was demonstrated in a hybrid of TGF beta-resistant bladder and colon carcinoma
      cells. In addition, T. cruzi did not efficiently invade epithelial cells with
      dysfunction of the intracellular signaling cascade caused by the constitutive
      expression of the cyclin-dependent kinase cdk4 or of the oncogene H-ras.
      Treatment with TGF beta, but not with other antiproliferative agents of non
      phagocytic cells, greatly enhances T. cruzi invasion. Moreover, infective, but
      not noninfective, trypanosomes strongly induce a TGF beta-responsive reporter
      gene in TGF beta-sensitive, but not in TGF beta-insensitive, cell lines. Thus, T.
      cruzi itself may directly trigger activation of the TGF beta signaling pathway
      required for parasite entry into the mammalian cells.

PMID- 7628018
TI  - Different levels of the C. elegans growth factor LIN-3 promote distinct vulval
      precursor fates.
AB  - An invariant spatial pattern of three cell fates (3 degrees-3 degrees-2 degrees-1
      degree-2 degrees-3 degrees) is generated from a field of multipotent precursor
      cells during C. elegans vulval development. We demonstrate that the epidermal
      growth factor-like domain of the LIN-3 protein can induce either of two distinct
      vulval cell fates: a high dose of LIN-3 induces a 1 degree fate; a lower dose of
      LIN-3 induces a 2 degrees fate. A high dose of LIN-3 can also induce adjacent
      vulval precursor cells to assume 1 degree fates; thus, high levels of LIN-3 can
      override the lateral signaling that normally inhibits formation of adjacent 1
      degree fates. We propose that the invariant pattern of vulval cell fates is
      generated by a graded distribution of LIN-3 that promotes different vulval fates
      according to local concentration and by a lateral signal that reinforces this
      initial bias.

PMID- 7628019
TI  - Male mice defective in the DNA mismatch repair gene PMS2 exhibit abnormal
      chromosome synapsis in meiosis.
AB  - Using gene targeting in embryonic stem cells, we have derived mice with a null
      mutation in a DNA mismatch repair gene homolog, PMS2. We observed microsatellite
      instability in the male germline, in tail, and in tumor DNA of PMS2-deficient
      animals. We therefore conclude that PMS2 is involved in DNA mismatch repair in a
      variety of tissues. PMS2-deficient animals appear prone to sarcomas and
      lymphomas. PMS2-deficient males are infertile, producing only abnormal
      spermatozoa. Analysis of axial element and synaptonemal complex formation during
      prophase of meiosis I indicates abnormalities in chromosome synapsis. These
      observations suggest links among mismatch repair, genetic recombination, and
      chromosome synapsis in meiosis.

PMID- 7628020
TI  - Inactivation of the mouse Msh2 gene results in mismatch repair deficiency,
      methylation tolerance, hyperrecombination, and predisposition to cancer.
AB  - To investigate the role of the presumed DNA mismatch repair (MMR) gene Msh2 in
      genome stability and tumorigenesis, we have generated cells and mice that are
      deficient for the gene. Msh2-deficient cells have lost mismatch binding and have
      acquired microsatellite instability, a mutator phenotype, and tolerance to
      methylating agents. Moreover, in these cells, homologous recombination has lost
      dependence on complete identity between interacting DNA sequences, suggesting
      that Msh2 is involved in safeguarding the genome from promiscuous recombination.
      Msh2-deficient mice display no major abnormalities, but a significant fraction
      develops lymphomas at an early age. Thus, Msh2 is involved in MMR, controlling
      several aspects of genome stability; loss of MMR-controlled genome stability
      predisposes to cancer.

PMID- 7628021
TI  - Postoperative pain management--back to basics.
AB  - Butscher describes a common-sense approach to pain management which is simple,
      safe and effective. A wide variety of national and international organization
      devoted to the management of pain have universally adopted these simple measures.
      Current guidelines advocate both regular dosing and rescue analgesia. These
      guidelines were produced by an army of international experts and have been
      available for a decade. Although the information is widely published, it is
      rarely adopted in clinical practice. It is any wonder that leaders in the field
      of pain management ask: "Is education enough?" "Will guidelines make a
      difference?" They continue to lament the "tragedy of needless pain" and in
      despair they have called for "national initiatives on pain." Bonica stated so
      elegantly, "for nearly 30 yr I have studied the reasons for inadequate management
      of postoperative pain, and they remain the same...inadequate or improper
      application of available information and therapies is certainly the most
      important reason for inadequate analgesia does not require futuristic high tech
      solutions. In fact, as the economic crunch continues we may find that we cannot
      afford some of these new, improved and more expensive techniques. If we can
      provide safe and effective analgesia for only pennies a day, this option cannot
      be ignored. The new way may be the old way.

PMID- 7628022
TI  - Routine use of preoperative antacids for children undergoing elective surgery.

PMID- 7628023
TI  - Can immediate opioid requirements in the post-anaesthesia care unit be used to
      determine analgesic requirements on the ward?
AB  - The aim of this prospective study was to evaluate the efficacy of two dosage
      regimens of (i.m.) morphine calculated from an initial (i.v.) titrated dose in
      the early postoperative period. Seventy ASA I-III patients who underwent general
      anaesthesia (GA) (n = 58), regional anaesthesia (RA) (n = 10) or GA+RA (n = 2)
      for orthopaedic (n = 54), urological (n = 11) or abdominal surgery (n = 5)
      received i.v. titrated morphine in the post-anaesthesia care unit (PACU).
      Titration consisted of 3 mg morphine i.v. every ten minutes until patients had a
      visual analogue pain scale (VAS) < 3, without marked sedation. Seventeen patients
      did not complain at all or had good analgesia with an initial i.v. dose < or = 6
      mg of morphine followed by paracetamol only. Patients who needed more than 6 mg
      i.v.morphine were randomly assigned to a "high-dose" or a "low-dose" group and
      received a systematic i.m. morphine regimen calculated from the initial titrated
      dose. Pain was assessed by VAS before each i.m. injection and the next morning.
      One patient had respiratory depression and one marked sedation in the PACU. These
      patients were excluded from the rest of the study. Only 16 patients were excluded
      from the rest of the study. Only 16 patients had a VAS > 3 at least once during
      the study period and only three needed rescue analgesia which was available on
      request. We conclude that a systematic i.m. morphine regimen adapted from an
      initial i.v. titration in the PACU provides efficacious and relatively
      inexpensive postoperative analgesia, applicable to a great majority of patients.

PMID- 7628024
TI  - Lansoprazole reduces preoperative gastric fluid acidity and volume in children.
AB  - The purpose of this study was to explore the efficacy of lansoprazole, a proton
      pump inhibitor, in reducing the acidity and volume of gastric aspirate in
      children immediately following the induction of anaesthesia. One hundred healthy
      in-patients aged 3-11 yr undergoing elective surgery were randomly allocated to
      four groups (n = 25 each): lansoprazole-lansoprazole, placebo-placebo, placebo
      lansoprazole, and lansoprazole-placebo. For each treatment regimen, the first
      medication was administered at 9:00 pm on the night before surgery and the second
      at 5:30 am on the morning of the day of surgery (three hours preoperatively). The
      dose of lansoprazole was 30 mg (approximately 1.4 mg.kg-1 mean). Children were
      offered 10 ml.kg-1 apple juice three hours before induction of anaesthesia. After
      induction of anaesthesia and tracheal intubation, gastric fluid was aspirated
      through a large-bore, multiorifice orogastric tube and analyzed for pH and total
      fluid volume. Lansoprazole increased gastric fluid pH and decreased gastric fluid
      volume regardless of whether it was administered before or after placebo. Two
      consecutive doses of lansoprazole was the most effective means of increasing the
      pH and reducing the volume of gastric aspirate; in this group, there were no
      subjects with gastric aspirate volume > 0.4 ml.kg-1 and pH < 2.5. Oral
      lansoprazole, at least 30 mg, given on the night before surgery or on the morning
      of surgery will improve the gastric environment at the time of induction of
      paediatric anaesthesia. The most effective regimen was two doses (at bedtime and
      on the morning) of lansoprazole.

PMID- 7628025
TI  - Premedication for ambulatory surgery in preschool children: a comparison of oral
      midazolam and rectal thiopentone.
AB  - Seventy five ASA 1 and 2 children, aged between six months and five years were
      randomized to receive oral midazolam 0.5 mg.kg-1, rectal thiopentone 35 mg.kg-1
      or no premedication to compare the safety and efficacy of, and parental attitudes
      to, both premedicants. Cardio-respiratory variables were from the time of
      premedication to awakening from anaesthesia. In addition, anxiety and sedation
      scores and patients' acceptance of both premedicant and mask at induction, were
      all recorded using four-point rating scales. Times to recovery and discharge, and
      parental satisfaction with the premedication their child had received were also
      recorded. Children receiving rectal thiopentone had higher sedation scores and
      were more accepting of the mask than were the other two groups (P < 0.001). Their
      acceptance of the premedication was similar to that of the midazolam group. Times
      to spontaneous eye opening and discharge were longer in the thiopentone group (P
      < 0.005). Parental preoperative satisfaction rating was higher for thiopentone,
      but not midazolam, than no premedication (P < 0.05). When asked their
      premedication preferences for subsequent general anaesthetics, a higher
      proportion of parents whose children were not premedicated requested an
      alternative regimen (P < 0.01). In conclusion the study found that premedication
      with rectal thiopentone provided superior induction characteristics to oral
      midazolam, but with a longer recovery period.

PMID- 7628026
TI  - Optimal placement of CVP catheter in paediatric cardiac patients.
AB  - For correct monitoring of central venous pressure (CVP) the tip of the CVP
      catheter should be placed in the superior vena cava (SVC). Since there is no
      useful guide for the optimal depth of insertion of CVP catheter in children
      undergoing cardiovascular surgery, we examined the relationship between the depth
      of the CVP catheter and easily measured body-size variables, such as age, weight
      and height, and then created a guide for the optimal placement of the paediatric
      population. The CVP catheterization was performed through the right internal
      jugular vein by the high approach. The position of the catheter tip was
      determined by the wave form of the CVP tracing and the depth of insertion was
      assessed by the external marking on the catheter at the cannulation site. The
      position of the catheter tip, determined by postoperative AP chest x-ray, was
      identified by the level of thoracic vertebra (T) corresponding to the position of
      the catheter tip. We analyzed the relationship between the depth of the catheter
      and patient's age, weight and height by linear regression analysis. The position
      of tip was normally distributed from T1 to T7 and the tips were centralized at
      levels of T3, T4 and T5 which anatomically correspond to SVC. The r values
      between the catheter depth and the three factors at each level were comparable,
      although the correlation between the depth of catheter and height was best. A
      simple guide for placement of the catheter tip at T3, T4 and T5 levels as a
      function of patient's height was created.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7628027
TI  - Butorphanol: an opioid for day-care paediatric surgery.
AB  - The purpose of this study was to compare the side effects and efficacy of
      equianalgesic doses of morphine (M) and butorphanol (B) in children undergoing
      similar surgical procedures associated with moderate postoperative pain. We
      studied 156 healthy children aged 1.5-13 yr who underwent elective inguinal
      herniorrhaphy or orchidopexy. After induction of anaesthesia subjects were given
      150 micrograms.kg-1 M or 30 micrograms.kg-1 B following a randomized, stratified,
      blocked and double-blind design. A standardized anaesthetic was administered,
      which included 1.5% halothane, vecuronium, droperidol and mechanical ventilation.
      The postsurgical four-hour follow-up included assessment of pain, vomiting and
      respiratory depression. Pain was assessed with mCHEOPS and analgesics were
      administered when indicated in the recovery room. Each opioid was administered to
      a group of 78 patients. Within each group, 25 subjects had an iv induction, 21
      children had an orchidopexy and 57 had inguinal hernia repairs. The groups were
      similar with respect to age, weight, and length of surgery. The choice of opioid
      did not affect recovery times from anaesthesia. Analgesic requirements were
      similar among the groups. Ten minutes after arrival in the recovery room the B
      subjects had a lower pain score than the M-patients. Postoperative vomiting was
      less among the B-subjects: 14% vs 28%, P = 0.03. Two M-patients required an
      unscheduled admission to hospital because of vomiting. It is concluded that
      butorphanol has few advantages over morphine in the population studied.

PMID- 7628028
TI  - Detection of intraoperative myocardial ischaemia--a comparison among
      electrocardiographic, myocardial metabolic, and haemodynamic measurements in
      patients with reduced ventricular function.
AB  - This study determined the sensitivity and specificity of haemodynamic and ECG
      monitors to detect the development of intraoperative myocardial ischaemia
      utilizing myocardial lactate production as the standard. In 29 patients with
      reduced ejection fraction (0.27-0.50) undergoing coronary artery
      revascularization, measurements were made at the awake, post-induction, post
      intubation, first skin incision, post-sternotomy, pre-protamine, immediately post
      cardiopulmonary bypass, and skin suture intervals. At each interval, measurement
      of a haemodynamic profile (including pulmonary artery occlusion (PAOP) and
      central venous (CVP) pressures, heart rate, and pressure rate quotient);
      myocardial lactate extraction and flux; changes in ST segments in ECG leads, V5
      and II utilizing a Siemens 1280 intraoperative monitor, and a Marquette 8500
      Holter monitor utilizing leads V5, V2, and AVF were made. "Ischaemia" was
      considered to be present when myocardial lactate production (MLP) occurred, PAOP
      or CVP increased by 5 mmHg above the baseline value, the pressure rate quotient
      was < 1, or ST segment deviation (> 1 mm) occurred in any lead for > 1 min.
      Variables positive when MLP was positive were the pressure rate quotient
      (sensitivity 32.8%, specificity 71.9%), CVP (sensitivity 10.9%, specificity
      92.6%), and PAOP (sensitivity 1.6%, specificity 99.2%). Holter monitoring had a
      100% positive predictive value but poor sensitivity (1.6%). The ECG (Lead V5 +
      II) measures of ischaemia were insensitive (17.5%) and relatively non-specific
      (87.7%). We conclude that, in this patient group and using myocardial lactate
      production as the standard, the pressure rate quotient, elevations in CVP or
      PAOP, or ST segment changes are insensitive measures of intraoperative myocardial
      ischaemia.

PMID- 7628029
TI  - Changes in respiratory compliance at laparoscopy: measurements using side stream
      spirometry.
AB  - In order to quantify changes in total respiratory compliance (Crs) effected by
      peritoneal pressurization we measured, under standardized anaesthetic conditions
      and using side stream spirometry Crs in 32 patients scheduled for abdominal
      surgery through laparoscopic techniques. To qualify the changes in Crs as to the
      type (duration and patient's position) of surgery, 20 patients having
      cholecystectomy, eight having gastric fundoplication, and four having inguinal
      hernia repair were studied. At CO2 insufflation to a mean intraabdominal pressure
      of 11 cmH2O in the horizontal position, Crs decreased abruptly by 20% in each of
      the surgical sub-groups (P < 0.05-0.01). During the insufflation period a further
      deterioration was observed, most pronounced in inguinal hernia patients operated
      upon in a head-down tilt position (P < 0.05). In the cholecystectomy and
      fundoplication patients, operated upon in a head-up tilt, the recovery of Crs was
      immediate at deflation, whereas an incomplete recovery (P < 0.05 vs initial
      values) was seen in the hernia patients. In evaluating all patients none of the
      demographic factors, age, sex, body-mass-index, intraabdominal pressure, or
      duration of pressurization, were associated with the detected changes.

PMID- 7628031
TI  - Evaluation of different methods of securing intravenous catheters: measurement of
      forces during simulated accidental pullout.
AB  - The purpose of the study was to compare the relative effectiveness of several
      combinations of tapes and taping methods with respect to the force required to
      pull out intravenous catheters. A simulated forearm model consisting of a section
      of firm PVC pipe was used for the first and second series of experiments. In the
      third experiment, one method of taping catheters was compared in the PVC model
      and in volunteers. Pullout forces were measured with a force transducer and
      recorded on paper. In the first experiment, catheters secured with Curity tape
      resisted pullout to a greater extent than those with Transpore tape and provided
      approximately twice the force advantage (P < 0.05). In the second experiment
      using Curity tape, minimum forces to dislodge the catheters were (means +/- SD)
      53 +/- 13, 82 +/- 13, 113 +/- 29, 124 +/- 24, 176 +/- 29 and 141 +/- 46 N, for
      methods 1-6, respectively. In the third series, the minimum pullout forces were
      higher for Curity than with Transpore tape for both the human and simulated PVC
      forearm surfaces (63 +/- 11 and 55 +/- 12 N vs 52 +/- 7 and 44 +/- 12 N, P <
      0.01), and the pullout forces were higher for the simulated vs. the human skin
      surface for both tape types (P < 0.01). Compared with Curity tape, Transpore tape
      was more likely to fail by tape fracture in both the simulated and human skin
      surfaces (P < 0.05). The data suggest that there are important differences in
      pullout forces and mechanisms of dislodgement depending on taping method and tape
      type.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7628030
TI  - Stability of the arterial to end-tidal carbon dioxide difference during
      anaesthesia for prolonged neurosurgical procedures.
AB  - This study was undertaken to examine the variation of the arterial to end-tidal
      PCO2 (Pa-PETCO2) difference during prolonged neurosurgical anaesthesia.
      Hyperventilation is often used to reduce intracranial pressure in neurosurgical
      patients. Continuous end-tidal CO2 monitoring is used as a guide between arterial
      CO2 measurements. We examined the stability of the Pa-PETCO2 difference in 21
      patients undergoing elective craniotomies lasting greater than four hours. A
      balanced neuroanaesthetic technique was used with the ventilation variables at
      the discretion of the attending anaesthetist. Once patients were positioned for
      surgery, simultaneous samples of arterial PCO2 through an arterial catheter, and
      end-tidal PCO2 via a mass spectrometer were obtained. The Pa-PETCO2 differences
      of each patient were plotted against time and a slope was derived with simple
      linear regression. The mean slope for all patients was then computed. There were
      no changes in the Pa-PETCO2 difference with time (P > 0.05) suggesting a constant
      relationship between the arterial and end-tidal PCO2 measurements over time. We
      conclude that end-tidal PCO2 can be used as a reliable guide to estimate arterial
      PCO2 during neurosurgical procedures of greater than four hours duration once the
      Pa-PETCO2 difference has been established.

PMID- 7628032
TI  - Oral clonidine does not alter vecuronium neuromuscular blockade in anaesthetized
      patients.
AB  - Since clonidine, an alpha 2-agonist, inhibits the release of norepinephrine or
      acetylcholine which can decrease nondepolarizing muscle relaxant-induced
      neuromuscular blockade, the authors examined whether clonidine given as an oral
      preanaesthetic medication would alter the onset, duration or recovery of a
      vecuronium neuromuscular blockade in lightly anaesthetized patients. Thirty-eight
      patients (aged 20-73 yr) randomly received oral clonidine either approximately 5
      micrograms.kg-1 (n = 21) or none (n = 17), 90 min before arrival in the operating
      room. We measured acceleration of thumb contraction with ulnar nerve stimulation
      at the wrist to assess neuromuscular blockade. The onset time (the time from
      injection to decrease to 5% of baseline twitch height), duration (the time
      interval between injection and return of the first twitch to 25% of the baseline
      value), and recovery index (the time interval of the first twitch from 25% to 75%
      of the baseline value) of neuromuscular blockade from a single bolus of
      vecuronium 0.1 mg.kg-1 i.v. were determined and compared between the clonidine
      treated and control patients during lower abdominal or extremity surgery under
      epidural plus general anaesthesia with fentanyl and nitrous oxide in oxygen. No
      differences were noted between the control and clonidine groups in onset time
      (100 +/- 6 sec (mean +/- SE) vs 101 +/- 6 sec), duration (44.5 +/- 2.7 min vs
      42.9 +/- 2.7 min), or recovery index (21.6 +/- 2.8 min vs 19.1 +/- 1.9 min) of
      neuromuscular blockade from vecuronium, respectively.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7628033
TI  - The introduction of new drugs into anaesthetic practice: a perspective in
      pharmaceutical development and regulation.
AB  - This article reviews the process by which new drugs are introduced into
      anaesthetic practice with particular emphasis on pharmaceutical development and
      government regulation. After a brief overview of the drug development process,
      new trends in drug development are discussed including implementation of
      pharmacokinetic, pharmacodynamic and toxicokinetic studies in both preclinical
      and human phases of drug evaluation. A synopsis of the drug regulatory process is
      provided and, in particular, the problem of unapproved drug use in anaesthesia is
      discussed. Ethical issues regarding physician-industry interactions are
      highlighted by examples of conflict of interest in anaesthesia. The processes of
      drug development and regulation require much effort and cooperation between
      clinicians, pharmaceutical manufacturers and government regulators to achieve a
      common goal; the development and utilization of safe and effective drugs. A
      fundamental understanding of these processes may further facilitate optimal drug
      utilization and the active involvement of anaesthetists in the drug development
      process.

PMID- 7628034
TI  - Laparoscopic extraperitoneal inguinal hernia repair complicated by subcutaneous
      emphysema.
AB  - The case of a healthy 59-yr-old man who underwent elective laparoscopic
      extraperitoneal inguinal hernia repair and general anaesthesia is presented.
      After one hour of surgery, a sudden increase in the FETCO2 from 5.0% to 9.4% in
      relation to a massive subcutaneous emphysema, but without any haemodynamic
      instability, was noticed. The acute rise of FETCO2 was the first sign of an
      abnormal event. Nevertheless, subcutaneous emphysema was diagnosed with chest
      wall examination and palpation. Subcutaneous emphysema and hypercarbia are
      potential complications of laparoscopic surgery, but are more likely to occur in
      extraperitoneal surgery, since insufflated CO2 can diffuse easily into the
      surrounding tissues. High insufflation pressures will increase chances of this
      occurring and was the most likely cause of this complication. This case
      encouraged us to make recommendations for the management of laparoscopic
      extraperitoneal surgery which included: monitoring of CO2 insufflation pressure,
      routine examination and palpation of chest wall, use of N2O with caution,
      adjusting ventilation to physiological FETCO2 and excluding other causes of
      subcutaneous emphysema and hypercarbia.

PMID- 7628035
TI  - An evaluation of the N-CAT, a new arterial tonometer.
AB  - The N-CAT is a newly developed arterial tonometer (TBP) monitor able to determine
      systolic, diastolic and mean blood pressures continuously and noninvasively. The
      aim of this study was to evaluate the accuracy and reliability of the TBP
      compared with directly measured invasive blood pressure (IBP) in 14 patients
      before and after elective coronary artery bypass surgery. Although the TBP was
      able to track changes in systemic pressure, before and after CPB, bias and
      precision for TBP monitoring did not meet the standard criteria for equivalency
      for noninvasive blood pressure to invasive blood pressure. We were unable to
      monitor TBP in two patients. Approximately 40% of all before and after CPB mean
      TBP pressure values differed from mean IBP by more than 10 mmHg. Moreover, there
      were discrepancies of sufficient magnitude and duration that limits the clinical
      usefulness of the N-CAT. Potential users should not rely exclusively on TBP
      values when making clinical decisions. Technological improvement is needed before
      its clinical use is recommended.

PMID- 7628036
TI  - Hyperalgesia during sedation: effects of barbiturates and propofol in the rat.
AB  - Subhypnotic doses of thiopentone are considered to possess antianalgesic or
      hyperalgesic properties. In this study, we have tested the hypothesis that the
      coincidence of sedation and hyperalgesia is a property of both barbiturate and
      non-barbiturate anaesthetic agents. In a randomized, prospective, blinded study,
      the effects of slow (20 min) iv infusions of thiopentone, pentobarbitone,
      methohexitone or propofol on nociceptive threshold were measured in rats by tail
      pressure analgesimetry and compared with saline-infused control animals.
      Nociceptive thresholds were correlated with measurements of plasma drug
      concentrations and behavioural assessments. Comparison of pre-infusion
      nociceptive threshold with the lowest threshold obtained during drug infusion
      revealed decreases in all four treatment groups. As a percentage of the pre
      infusion values, the decreases were: thiopentone: 42.5% (P < 0.001),
      pentobarbitone: 27.8% (P = 0.014), methohexitone: 24.9% (P = 0.013), propofol:
      21.6% (P = 0.006). There were no changes in nociceptive threshold in the control
      groups. The relationship between nociceptive threshold and plasma drug
      concentration was usually characterized by an initial decline followed by a rise
      in nociceptive threshold as the plasma concentration and degree of sedation
      increased. The results support the hypothesis that hyperalgesia is a property of
      different anaesthetic agents when administered at sub-hynotic concentrations.

PMID- 7628037
TI  - Attenuation of morphine-induced antinociception by L-glutamic acid at the spinal
      site in rats.
AB  - The present experimental study was planned to evaluate the effect of intrathecal
      administration of L-glutamic acid upon antinociception produced by intrathecal
      morphine in a prospective-controlled manner in conscious freely mobile Sprague
      Dawley albino rats. After chronic catheterization of the spinal subarachnoid
      space, rats were randomly allocated into 12 treatment groups of ten each and the
      same number of rats served as saline control for the comparison. L-glutamic acid
      (100 mmol), morphine (1.2 mmol), ketamine (50 mmol) and saline (150 mmol) were
      injected intrathecally in 5 microliters volumes. Naloxone was injected in a dose
      of 1 mg.kg-1 im. Immediately before and 15, 30 min, 1, 2 and 3 hr after
      injection, rats were subjected to a thermal noxious stimulus, using a tail-flick
      technoanalgesiometer and tail-flick latencies (TFL) were recorded. Intrathecal
      administration of L-glutamic acid attenuated the antinociceptive effect of
      intrathecal morphine with a decrease in TFL (1.4 +/- 0.3 sec; P < 0.0001) from
      6.6 +/- 0.3 sec. Ketamine led to abolition of this effect (P < 0.01). In rats,
      pretreated with naloxone, there was restoration as well as augmentation of
      morphine-induced antinociception in the presence of L-glutamic acid with an
      increase in TFL (9.0 +/- 0.4 sec; P < 0.0001). We conclude that there is
      modulation of opioid receptors by L-glutamic acid at the spinal site in rats.

PMID- 7628038
TI  - Pulmonary resistance in dogs: a comparison of xenon with nitrous oxide.
AB  - Xenon (Xe) may cause an increase in airway resistance due to its high density and
      viscosity. The object of this study was to examine the effects of Xe on pulmonary
      resistance using dog models with normal and methacholine-treated airways. During
      anaesthesia 22 mongrel dogs' tracheas were intubated and the lungs were
      mechanically ventilated with 70% N2/30% O2 as a control gas. The gases 70%
      nitrous oxide (N2O), 50% N2O, 70% Xe and 50% Xe were administered in a random
      order for 25 min. Bronchoconstriction was produced by a continuous infusion of
      methacholine, 0.22 mg.kg-1.hr-1. Pulmonary resistance (RL) was calculated by the
      isovolume method using flow at the airway opening, volume and transpulmonary
      pressure. In normal dogs, RL breathing 70% Xe (mean +/- SEM, 0.84 +/- 0.12 cm
      H2O.L-1.sec-1) was greater (P < 0.05) than with 70% N2O, 50% N2O or control gas
      (0.61 +/- 0.08, 0.59 +/- 0.06 and 0.62 +/- 0.06 cmH2O.L-1.sec-1). Breathing 50%
      Xe the RL (0.77 +/- 0.10 cmH2O.L-1.sec-1) was not different from 50% N2O or
      control. Methacholine infusion increased RL 3.92 +/- 1.98 (mean +/- SD) times.
      The RL breathing 50% Xe (2.55 +/- 0.44 cmH2O.L-1.sec-1) was not greater than
      during 50% N2O or control (2.08 +/- 0.33 and 2.13 +/- 0.33 cmH2O.L-1.sec-1) in
      methacholine-treated dogs. The data suggest that inhalation of high
      concentrations of Xe increases airway resistance, but only to a modest extent in
      dogs with normal or methacholine-treated airways.

PMID- 7628039
TI  - Did you have anything to eat, drink, or maybe, chew?

PMID- 7628040
TI  - Epidural analgesia in children.

PMID- 7628041
TI  - Trans-tracheal jet ventilation.

PMID- 7628042
TI  - CABS and CSEGA ...

PMID- 7628043
TI  - Pneumothorax during fundoplication.

PMID- 7628044
TI  - Addition of clonidine and fentanyl to epidural blockade with 0.5% bupivacaine.

PMID- 7628045
TI  - Intracellular glutathione and cytotoxicity of platinum complexes.
AB  - Although there have been a number of reports correlating cellular GSH levels with
      cytotoxicity of platinum agents, none has examined the relationship between GSH
      concentrations and cytotoxicity. In this study, using a highly specific HPLC
      method for measuring GSH and expressing GSH as concentration and also per cell
      number, we evaluated the correlation between GSH levels and the cytotoxicity to
      five agents in ten human tumor cell lines. The five platinum agents included the
      platinum(II) complexes cisplatin, carboplatin and oxaliplatin and platinum(IV)
      complexes iproplatin and tetraplatin. The correlation between intracellular GSH
      concentration and cytotoxicity was highly significant only for iproplatin (P =
      0.002) followed by tetraplatin, which demonstrated a trend toward statistical
      significance (P = 0.06). Cytotoxicity of the other platinum complexes showed no
      relation to GSH concentration, cisplatin itself showing a P-value of 0.09. In
      contrast, the GSH levels normalized to cell number showed a statistically
      significant correlation with the cytotoxicity of four of the five platinum
      agents, the exception being carboplatin; the strongest correlation observed was
      that for iproplatin and tetraplatin. Glutathione-S-transferase (GST) activity in
      these cell lines showed no correlation with cytotoxicity of any of the platinum
      complexes. Our results, from the analyses of both GSH concentration as well as
      GSH per cell number, suggest a significantly higher interaction between GSH and
      iproplatin compared with the other platinum agents. Moreover, our data suggest
      that relationships between cytotoxicity and GSH levels on a per-cell basis may
      not persist when differences in cell volume are taken into account.

PMID- 7628047
TI  - Antidote studies of vinorelbine-induced skin ulceration in the mouse.
AB  - The new cantharanthine-modified vinca alkaloid vinorelbine (Navelbine) was
      administered intradermally (ID) to dehaired BALB/c mice. Dose-dependent skin
      lesions were produced over the range 0.01-0.5 mg/mouse, with complete healing
      after 9-35 days. Local (ID) injections of hydrocortisone and saline were
      ineffective at blocking vinorelbine-induced skin ulceration. Topical skin heating
      to 43 degrees C or cooling to 10 degrees C were also ineffective. In contrast,
      hyaluronidase, 15 Units ID, following vinorelbine significantly reduced skin
      lesions. These results show that vinorelbine is a vesicant and that inadvertent
      extravasations may be managed with subcutaneous injection of the spreading factor
      enzyme, hyaluronidase.

PMID- 7628046
TI  - Pharmacokinetics of different doses of methotrexate at steady state by in situ
      microdialysis in a rat model.
AB  - We used a microdialysis technique to monitor extracellular methotrexate (MTX)
      levels during the steady state in a rodent model. Microdialysis probes were
      implanted in the muscle, liver, and kidney of anesthetized male Wistar rats. MTX
      (18.75-500 mg/kg) was given as a continuous infusion through a venous catheter,
      and blood samples were obtained through a second venous catheter. Heparinized
      plasma, ultrafiltered plasma, microdialysis effluent from tissues, and tissue
      samples (obtained at the end of experiments) were analyzed for MTX content by
      high-performance liquid chromatography (HPLC). Steady state was demonstrated in
      the blood and tissues from 2 h until the end of the experiments (6 h).
      Extracellular drug levels in muscle and liver displayed a linear correlation with
      doses, whereas kidney levels reached a plateau at an MTX dose of 150 mg/kg per 6
      h. Microdialysis-fluid endpoint levels for muscle, liver, and kidney were
      positively correlated to the endpoint total tissue levels (r2 = 0.80, 0.85, and
      0.68, respectively). In the kidneys, the maximal relative tissue MTX accumulation
      was measured at a total dose of 75 mg/kg per 6 h. At higher doses, the relative
      drug sequestration declined to less than half of the values observed at this
      dose. This study demonstrates that the microdialysis technique can provide
      reproducible data on MTX tissue exposure in an animal model and that it offers a
      means of serial and reproducible monitoring of extracellular-tissue MTX levels at
      steady state and over a wide dose range. Pending additional studies,
      microdialysis may be a helpful technique for elucidating the kinetics of drug
      delivery to both targeted and toxicity-prone tissues during chemotherapy.

PMID- 7628048
TI  - Phase I study of mitomycin C and menadione in advanced solid tumors.
AB  - A phase I study of mitomycin C with menadione (2-methyl-1,4-naphthoquinone, a
      vitamin K analogue which lowers intracellular pools of reduced glutathione) was
      designed as an approach to overcoming tumor cell resistance to alkylating agent
      chemotherapy. Patients with refractory solid tumors (n = 51) were treated with a
      48-h continuous intravenous infusion of menadione followed by a bolus intravenous
      dose of mitomycin C at the completion of the menadione infusion. Initial
      menadione doses of 8.0 and 4.0 g/m2 over 48 h were associated with hemolysis, so
      subsequent dose levels of menadione ranged from 1.0 to 3.0 g/m2 with mitomycin C
      from 5 to 20 mg/m2. All three patients treated with menadione at 8.0 g/m2 and the
      single patient treated at 4.0 g/m2 with mitomycin C at 5 mg/m2 developed
      clinically significant hemolysis despite the presence of red blood cell glucose-6
      phosphate dehydrogenase. Subsequently, a revised escalation scheme for menadione
      was used, and all patients tolerated menadione doses of 1-2.5 g/m2 over 48 h with
      mitomycin C doses up to 20 mg/m2. Since the 3.0 g/m2 dose of menadione was
      associated with mild hemolysis in three of four patients, the maximum tolerated
      dose of menadione was established at 2.5 g/m2. All of the mitomycin dose levels
      were tolerated without unexpected toxicities attributable to the combination.
      Prolonged infusions of menadione at doses which have been associated with
      lowering of intracellular glutathione pools in short-term exposure are limited by
      dose-dependent hemolysis, probably due to depletion of erythrocyte glutathione by
      menadione-related redox cycling. There was no detectable deleterious effect of
      pre-exposure to menadione on mitomycin C tolerance. We recommend a combination of
      menadione at 2.5 g/m2 as a continuous intravenous infusion and mitomycin C at 15
      mg/m2 for further study in solid tumors, for which treatment with single-agent
      mitomycin C is appropriate.

PMID- 7628049
TI  - Isolation, purification, and biological activity of mono- and dihydroxylated
      paclitaxel metabolites from human feces.
AB  - Three metabolites of the cytotoxic drug paclitaxel (Taxol) were isolated and
      purified from the feces of cancer patients receiving the agent as an intravenous
      infusion. The procedures involved sample homogenization in water followed by
      liquid-liquid extraction with diethyl ether and high-performance liquid
      chromatography (HPLC). Approximately 1-3.5 mg of each metabolite was obtained
      from 100 g of feces. As judged from the chromatographic traces of analytical HPLC
      with ultraviolet (UV) detection at 227 nm, the purity of each compound was > 97%.
      On-line photodiode-array detection demonstrated that the UV spectrum of the
      isolated compounds closely resembles that of the parent drug. Mass spectrometry
      provided evidence that these metabolites are mono- and dihydroxy-substituted
      derivatives, namely, 6 alpha-hydroxypaclitaxel, 3'-p-hydroxypaclitaxel, and 6
      alpha, 3'-p-dihydroxypaclitaxel. The two 6 alpha-hydroxy-substituted metabolites
      were shown to have lost their cytotoxicity in in vitro clonogenic assays using
      the A2780 human ovarian carcinoma and the CC531 rat colon-carcinoma tumor cell
      lines. In addition, the metabolites showed reduced myelotoxic effects as compared
      with paclitaxel in an in vitro hemopoietic progenitor toxicity assay. Our
      procedure for the isolation and purification of paclitaxel metabolites in
      milligram quantities should be useful for testing the biological activities of
      these compounds and for the preparation of calibration standards essential for
      pharmacokinetics studies.

PMID- 7628050
TI  - Preclinical pharmacologic evaluation of geldanamycin as an antitumor agent.
AB  - The plasma pharmacokinetics of the anti-tumor antibiotic geldanamycin (GM: NSC
      122750), a naturally occurring benzoquinoid ansamycin, was characterized in mice
      and a beagle dog. Concentrations of GM well above 0.1 microgram/ml, which was
      typically effective against neoplastic cell lines responsive to the drug in
      vitro, were achieved in the plasma of the mice and the dog treated by i.v.
      injection. However, the systemic duration of the drug was relatively short.
      Plasma levels decayed below 0.1 microgram/ml within 3-4 h after administration of
      the apparent maximum tolerated doses, which were approximately 20 mg/kg for the
      mice and 4 mg/kg for the dog. The drug exhibited linear pharmacokinetic behavior
      within the dose ranges studied. However, there were significant interspecies
      differences in its disposition. Whereas the mean biological half-life of GM was
      slightly longer in the mice (77.7 min) than in the dog (57.9 min), its mean
      residence time in the dog (46.6 min) was more than twofold greater than that
      observed in the mice (20.7 min). Nevertheless, the drug was cleared from plasma
      much faster by the dog (49.4 ml/min per kg) than by the mice (30.5 ml/min per
      kg). These apparent anomalies were principally associated with differences in the
      relative significance of the terminal phase upon overall drug disposition. The
      liver appeared to be the principal target organ of acute drug toxicity in the
      dog. Doses of 2.0 and 4.2 mg/kg both produced elevations in serum levels of the
      transaminases and other indicators of liver function characteristic of acute
      hepatic necrosis. Additional effects included symptoms of minor gastrointestinal
      toxicity and alterations in serum chemistry parameters consistent with less
      severe nephrotoxicity. Drug-related toxicity appeared to be reversible. In
      consideration of the potential for acute hepatotoxic reactions to GM, as well as
      to the other benzoquinoid ansamycins based upon structural analogy, additional
      pharmacological and therapeutic information is required to ascertain whether
      these compounds are viable candidates for clinical development.

PMID- 7628051
TI  - Protein binding modulates inhibition of the epidermal growth factor receptor
      kinase and DNA synthesis by tyrphostins.
AB  - Inhibition of growth factor-stimulated DNA synthesis carried out in defined
      medium is often compared with inhibition of serum-stimulated DNA synthesis so as
      to assess the selectivity of growth-factor-receptor tyrosine kinase inhibitors
      such as tyrphostins. We investigated whether protein binding may influence the
      interpretation of these experiments. Protein binding of tyrphostins was
      determined by ultrafiltration, equilibrium dialysis or spectrophotometer, and was
      quantitated by high-performance liquid chromatography (HPLC). For growth factor
      stimulated DNA synthesis, we used the non-small-cell lung cancer cell line L23/P
      stimulated by transforming growth factor alpha (TGF alpha). The epidermal growth
      factor (EGF)-receptor kinase was assayed by phosphorylation of a peptide
      substrate or by receptor autophosphorylation. Protein binding of a number of
      tyrphostins ranged from 64% to 98%. There was a positive correlation (r = 0.995)
      between the degree of protein binding and the hydrophobicity. Inhibition of the
      EGF-receptor tyrosine kinase activity by the highly protein-bound tyrphostin B56
      [N-(4-phenylbutyl)-3,4-dihydroxybenzylidene cyanoacet-amide] was reduced by
      bovine serum albumin (BSA), but BSA had less of an effect on inhibition of the
      EGF-receptor kinase by the weakly protein-bound tyrphostin A47 (RG 50864: 3,4
      dihydroxybenzylidene cyanothioacetamide). Tyrphostins B46 [N-(3-phenylpropyl)-3,4
      dihydroxybenzylidene cyanoacetamide] and B56 (both highly protein-bound)
      inhibited DNA synthesis of L23/P cells with approximately 3-fold greater potency
      in 0.5% serum than in 10% serum, but the inhibition of DNA synthesis in 0.5%
      serum was reduced by the addition of BSA. Tyrphostins B46 and B56 inhibited DNA
      synthesis stimulated by TGF alpha in defined medium to a greater extent than DNA
      synthesis stimulated by serum. However, this apparent selectivity for inhibition
      of TGF alpha-stimulated DNA synthesis was lost when the protein concentration in
      the defined medium was made equivalent to that in the serum-containing medium. By
      contrast, BSA enhanced the selective inhibition of TGF alpha-stimulated DNA
      synthesis by tyrphostin A47. These results demonstrate that protein binding
      accounts for the apparent selectivity of some highly protein-bound tyrphostins
      for TGF alpha-stimulated DNA synthesis of L23/P cells. Therefore, protein binding
      should be taken into consideration in assessments of the selectivity of
      tyrphostins.

PMID- 7628052
TI  - Selective inhibition of cell proliferation and DNA synthesis by the polysulphated
      carbohydrate l-carrageenan.
AB  - l-Carrageenan is a polysulphated carbohydrate that antagonises some heparin
      binding growth factors. We assessed the effect of l-carrageenan on the
      proliferation of a panel of cell lines, some of which require heparin-binding
      growth factors for mitogenesis. The importance of growth factor antagonism for
      the anti-proliferative activity was also determined. Cell proliferation was
      determined by cell counts and a tetrazolium dye (MTT) assay, and DNA synthesis
      was determined by thymidine incorporation. The proliferation of the basic
      fibroblast growth factor (bFGF)-dependent endothelial cell line FBHE was
      inhibited by daily administration of l-carrageenan in a dose-dependent manner
      [concentration inhibiting cell growth by 50% (IC50 value), approx. 0.5
      microgram/ml]. However, excess bFGF did not reverse the inhibitory effect. DNA
      synthesis was completely inhibited by concentrations of l-carrageenan that
      nonetheless allowed significant protein synthesis to occur. The proliferation of
      the androgen-dependent prostate-carcinoma cell line LNCaP was also inhibited by l
      carrageenan (IC50 value, 5.5 micrograms/ml) and the cells were arrested at the
      G1/S boundary. l-Carrageenan inhibited DNA synthesis in MCF-7 cells stimulated by
      bFGF and transforming growth factor alpha (TGF alpha) but not in those stimulated
      by insulin-like growth factor 1 (IGF-1). Blocking IGF-1-mediated DNA synthesis
      with anti-IGF-1 receptor antibody alpha IR3 enhanced the inhibitory activity of l
      carrageenan against MCF-7 cells grown in serum. A number of other transformed and
      non-transformed cell lines were either partially inhibited or not inhibited by l
      carrageenan. l-Carrageenan had low anti-coagulant activity. l-Carrageenan is a
      selective anti-proliferative agent and warrants further investigation for anti
      angiogenic therapy (in view of its activity against endothelial cells) and for
      the treatment of androgen-dependent prostate cancer.

PMID- 7628053
TI  - Changes in doxorubicin distribution and toxicity in mice pretreated with the
      cyclosporin analogue SDZ PSC 833.
AB  - SDZ PSC 833 (PSC 833) is a cyclosporin A analogue that is under clinical
      investigation in combination with doxorubicin (Dx) or other anticancer agents as
      a type-1 multidrug resistance (MDR-1)-reversing agent. The present study was
      focused on the effects of PSC 833 on the distribution and toxicity of Dx in non
      tumor-bearing CDF1 male mice. Mice were given PSC 833 i.p. at 30 min before i.v.
      Dx treatment. Dx levels were determined by a high-performance liquid
      chromatography (HPLC) assay at different times during a 72-h period following Dx
      treatment in the serum, heart, intestine, liver, kidney, and adrenals of mice. In
      all tissues, Dx area under the concentration-time curve (AUC) values were much
      greater in mice receiving 10 mg/kg Dx in combination with 12.5 or 25 mg/kg PSC
      833 than in mice receiving Dx alone. The highest increase in Dx concentrations
      was found in the intestine, liver, kidney, and adrenals. Lower, albeit
      significant, differences were found in the heart. PSC 833 did not appear to
      influence either urinary or fecal Dx elimination or Dx metabolism to a great
      extent. Doses of PSC 833 devoid of any toxicity potentiated the acute and delayed
      toxicity of Dx dramatically. The mechanism responsible for this enhanced toxicity
      has not yet been elucidated but is likely to be related to an increased tissue
      retention of Dx due to inhibition of the P-glycoprotein (Pgp) pump by PSC 833, as
      has recently been proposed for cyclosporin A.

PMID- 7628054
TI  - Mechanism of potentiation of LY83583-induced growth inhibition by sodium
      nitroprusside in human brain tumor cells.
AB  - The effect of 6-anilino-5,8-quinolinedione (LY83583), an inhibitor of guanylyl
      cyclase (GC), on the growth of human brain tumor cells (U-373 MG astrocytoma and
      SK-N-MC neuroblastoma) was evaluated. LY83583 inhibited the growth of these cells
      in a dose-dependent manner. This growth inhibition was found to be the result of
      decreased cell viability as assessed by the trypan blue exclusion method. The
      LY83583-induced decrease in cell viability was not altered by dibutyryl cyclic
      GMP, but significantly was reversed by superoxide dismutase and catalase,
      indicating that these effects of LY83583 may not be due to the inhibition of GC,
      but due to the formation of superoxide anion. The LY83583-induced decrease in
      cell viability was potentiated by cotreatment with sodium nitroprusside (SNP), a
      nitric oxide (NO) donor. This SNP-induced potentiation was significantly blocked
      by various scavengers for hydroxyl radicals or by intracellular Ca2+ release
      blockers. These results suggest that the potentiation effects of SNP may be
      mediated through the generation of hydroxyl radicals which can be formed by the
      interaction of superoxide anion (from LY83583) and NO (from SNP), and that
      intracellular Ca2+ release from internal stores may play an important role in the
      cytotoxic mechanism of hydroxyl radicals.

PMID- 7628055
TI  - High-dose ifosfamide, carboplatin, and etoposide pharmacokinetics: correlation of
      plasma drug levels with renal toxicity.
AB  - An autologous bone marrow transplant regimen of ifosfamide, carboplatin, and
      etoposide (ICE) has been developed as treatment for certain malignancies. At
      maximum tolerated doses renal insufficiency precludes dose escalation. The
      objective was to examine whether measurement of plasma drug levels early during
      treatment would provide warning of renal failure. Nine patients received a 96-h
      continuous infusion of ifosfamide 16,000 mg/m2, carboplatin 1600 mg/m2, and
      etoposide 1200 mg/m2. Pharmacokinetics, including drug levels and plasma
      concentration-time curves, of ifosfamide, ultrafiltrable platinum (uPt) and
      etoposide were analyzed and correlated with renal function. One of the nine
      patients developed anuric renal failure requiring hemodialysis. By 17 h from the
      start of infusion, this patient showed substantially higher drug levels of
      ifosfamide (200 vs mean 217 microM) and uPt (19 vs mean 10 microM) than those
      patients with preserved renal function. The 95% confidence intervals suggested
      that a 16-22 h ifosfamide level > 153 microM and an uPt level > microM predict
      the development of significant renal dysfunction. Although drug levels were
      substantially higher at 56 h, the serum creatinine did not yet reflect kidney
      injury. This study suggests that high plasma ifosfamide and uPt levels, analyzed
      early in the course of a 96-h infusion of high-dose ICE, provide warning of
      severe and potentially fatal renal injury. Since ICE has substantial activity in
      a number of malignancies, but significant renal morbidity, real-time
      pharmacokinetic-guided dosing may reduce treatment-related toxicity.

PMID- 7628056
TI  - Pharmacokinetic evaluation of two different formulations of megestrol acetate in
      patients with advanced malignancies.
AB  - The bioequivalence of two megestrol acetate formulations, 160-mg "tablets" and
      160-mg "sachets," was investigated in a single-dose, open-label, balanced-for
      sequence cross-over study involving 12 advanced-cancer patients. The observed
      plasma megestrol-acetate time course obtained with both formulations was
      consistent with the literature data. The main source of variability in the
      pharmacokinetic parameters was intersubject variability; drug formulation played
      only a minor (and nonsignificant) role. The width of the 90% confidence interval
      of the area-under-the-curve (AUC) ratio (sachets: tablets) computed according to
      Schuirmann (0.9-1.4) was mainly due to the presence of a single outlier, showing
      an AUC ratio of 2.7. The trend to higher bioavailability of the new formulation
      was not significant, especially as compared with the dose-response data reported
      in the literature.

PMID- 7628057
TI  - Lysozyme regulates LPS-induced interleukin-6 release in mice.
AB  - Bacterial lipopolysaccharide (LPS) stimulates the production and release of
      endogenous mediators [e.g., tumor necrosis factor (TNF), interleukins-1 and -6
      (IL-1 and IL-6), and Platelet Activating Factor [PAF] responsible for the
      pathophysiologic changes and the mortality associated with sepsis. We recently
      demonstrated that lysozyme (LZM) bound to LPS (LZM-LPS complex) suppresses LPS
      induced tumor necrosis factor-alpha (TNF-alpha) production in vivo. In the
      present study, we investigated the effect of LZM-LPS complex formation on LPS
      induced IL-6 production, both in vitro and in vivo. With the addition of LZM-LPS
      complex, TNF-alpha and IL-6 release was significantly reduced compared with that
      by LPS in a dose-dependent manner in mouse macrophage-like cells, RAW264.7. IL-6
      production in serum by LPS in carrageenan (CAR)-primed mice peaked at 2 hr
      following injection. LZM-LPS and LZM-Escherichia coli cell complex (as 1
      microgram of LPS per mouse) released significantly reduced concentrations of IL-6
      in serum (P < 0.01 and P < 0.001 versus CAR-pretreated LPS- or cell-injected
      mice). These results emphasize the important role of LZM in vivo in the
      neutralization of endotoxin. However, in the case of IL-6, by administration of a
      lethal dose of LPS (as 100 micrograms of LPS per mouse), the IL-6 level was
      reduced by LZM, but a significant concentration of IL-6 was still released;
      although the TNF- alpha concentration was negligible in this experimental
      condition. Thus, it is suggested that LZM might regulate the systemic
      inflammation induced during Gram-negative bacterial infections by inhibiting the
      release of cytokines in serum.

PMID- 7628058
TI  - Liver oxygen uptake dependence and mitochondrial function in septic rats.
AB  - Defective oxygen consumption and a pathological dependence of oxygen uptake on O2
      supply have been considered important events in sepsis. To relate these features
      with tissue and mitochondrial metabolism, we studied oxygen uptake in whole
      isolated and perfused rat liver at two O2 supply levels, in the same liver
      slices, and in isolated liver mitochondria. Experimental sepsis in rats was
      induced by cecal ligation and double-gauge puncture. The results showed that
      liver and tissue slices from septic animals had a 60% greater O2 uptake than that
      of controls and that, during sepsis, liver O2 uptake was markedly dependent on O2
      supply. Concomitantly, mitochondrial O2 uptake was nearly 30% greater with malate
      glutamate as substrate, but not with succinate; lowering O2 concentration in the
      medium did not alter the enhanced function. In submitochondrial, only NADH
      dehydrogenase activity was 100% higher in septic samples. At least, in some
      tissues, O2 dependence is a function of O2 availability, sensitized by increased
      mitochondrial O2 uptake related to changes in respiratory enzymes.

PMID- 7628059
TI  - Efficacy of continuous arteriovenous hemofiltration in endotoxic shock.
AB  - We determined the efficacy of continuous arteriovenous hemofiltration (CAVH) in
      removing tumor necrosis factor (TNF), thromboxane A2, and prostacyclin, and in
      improving survival in endotoxemia. Twelve rats were given 10 mg/kg of E. coli
      0:127:B8 lipopolysaccharide. Fifteen min later, the rats were randomized to
      ultrafiltered or non-ultrafiltered groups. Blood and ultrafiltrate were collected
      for TNF, thromboxane B2 (TxB2), and 6-keto-prostaglandin F1 alpha (6-keto-PGF1
      alpha). After 4 hr, surviving rats were sacrificed. Five of 6 ultrafiltered and
      none of 6 non-ultrafiltered rats survived 4 hr. Plasma TxB2 > 1,000 pcg/ml and
      its rate of increase within the first 2 hr predicted death (P < 0.03).
      Ultrafiltration decreased the rate of rise in TxB2 (P < 0.04). Plasma TxB2
      inversely correlated with TxB2 clearance by ultrafiltration. The concentration
      and rate of increase in TNF and 6-keto-PGF1 alpha did not predict survival. We
      conclude that CAVH improves short term survival in endotoxemia. Salutary effects
      appear to be due to thromboxane A2 removal.

PMID- 7628060
TI  - Beneficial effects of the phosphodiesterase inhibitors BRL 61063, pentoxifylline,
      and rolipram in a murine model of endotoxin shock.
AB  - Three inhibitors of calcium-dependent cyclic adenosine 3'5'-monophosphate (cAMP)
      dependent phosphodiesterase IV (PDE IV) were evaluated for their effects on
      lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF) production in vitro
      and in vivo and for their ability to protect mice from LPS-induced lethality in D
      galactosamine (D-gal) sensitized mice. In vitro, on LPS-stimulated murine
      peritoneal macrophages (PEM), BRL 61063 (1,3-di(cyclopropylmethyl)-8
      aminoxanthine) and rolipram (4-(3-cyclopentyloxy-4-methoxyphenyl)-2-pyrrolidone)
      had similar TNF inhibitory activity with an IC50 ranging from 0.1 to 0.5 microM.
      Pentoxifylline (PTX), (3,7-dimethyl-1-(5-oxohexyl)xanthine) was less potent with
      an IC50 = 100 microM. In vivo, there was a rank order potency on serum TNF levels
      in LPS challenged D-gal sensitized mice. BRL 61063 inhibited TNF production with
      an ID50 of 0.1 mg/kg, rolipram at 1 mg/kg, and PTX at 200 mg/kg. Thus, BRL 61063
      is 2,000 times more potent than PTX in reducing TNF serum levels in this model.
      Interestingly, TNF is implicated as having a central pathogenic role in the LPS/D
      gal model, since survival of animals correlated directly with reduction of serum
      TNF levels for all three compounds tested. It is proposed that potent inhibitors
      of TNF may have therapeutic activity in disease states where TNF appears to play
      a role in the pathogenesis of the disease.

PMID- 7628061
TI  - Functional requirement of the two TNF receptors for induction of apoptosis in
      PC60 cells and the role of mitochondria in TNF-induced cytotoxicity.
AB  - The rat/mouse T-cell hybridoma PC60 was transfected either with hTNF-R55 cDNA,
      hTNF-R75 cDNA, or both. Receptor-specific stimulation was achieved using
      agonistic monoclonal antibodies or receptor-specific muteins of hTNF. Either hTNF
      R55 or hTNF-R75 could mediate the activation of NF-kappa B and the induction of
      GM-CSF, IL-6, and IFN-gamma. But only in cells carrying both hTNF-R55 and hTNF
      R75, was TNF able to induce apoptosis. This apoptosis could be inhibited almost
      completely by cotransfection with human bcl-2 cDNA. Functional cooperation was
      observed between liganded and unliganded receptors for the induction of
      apoptosis. In vitro protein kinase activity was detected only in TNF-R75
      immunoprecipitates from cells in which the receptor was signaling. Direct
      evidence was obtained for reactive oxygen intermediates of mitochondrial origin
      responsible for TNF-induced cytotoxicity in L929 cells.

PMID- 7628062
TI  - Endothelin-1 causes accumulation of leukocytes in the pulmonary circulation.
AB  - We previously reported that the endothelin-1 (ET-1)-induced increase in
      microvascular permeability in isolated rat lungs required leukocytes in the
      perfusate. The present study examines whether intravenous administration of ET-1
      in rats causes an inflammatory reaction in the lungs. Histological examination of
      the lung specimens 2 hr following ET-1 infusion showed adhesion of leukocytes to
      the vascular endothelium in pulmonary vessels and sequestration of leukocytes in
      the pulmonary capillaries. Microscopic examination of the bronchoalveolar lavage
      fluid revealed that leukocytes had migrated into the alveoli. Simultaneously a
      depletion of peripheral blood leukocytes was observed. These effects were
      reversible by 24 hr. Monitoring of systemic hemodynamic effects showed a
      continued reduced cardiac stroke volume and increasing heart rate after 2 hr. In
      isolated rat lungs, ET-1 caused a rapid increase in pulmonary artery pressure,
      pulmonary microvascular pressure, and edema formation. Compared with Krebs
      albumin-perfused lungs, blood-perfusion accelerated the edemagenic effect of ET
      1. ET-1 plays a role in the regulation of leukocyte-endothelial cell interactions
      in the pulmonary circulation. This has potential importance for the edemagenic
      effect of ET-1.

PMID- 7628063
TI  - Endocrine and carbohydrate responses to interleukin-6 in vivo.
AB  - The role of interleukin-6 (IL-6) in carbohydrate metabolism beyond its inhibition
      of hepatic phosphoenolpyruvate carboxykinase has not been widely pursued. To
      describe such IL-6 effects, we examined in the rat the responses of plasma
      corticosterone, glucagon, insulin, and glucose levels and the hepatic glycogen
      content 30, 60, 90, 120, and 180 min after intravenous injection of recombinant
      human IL-6. The effect to increase plasma corticosterone was consonant with the
      well-known action of IL-6 on the hypothalamus-pituitary-adrenal cortex. IL-6
      produced a transient increase in plasma glucagon that was mirrored by elevated
      plasma glucose and a depletion of hepatic glycogen. Plasma insulin levels were
      not elevated within the first hour after IL-6 injection but were significantly
      elevated 90 min and beyond. We suggest that the stimulus for increased
      circulating insulin was elevated plasma glucose, rather than a direct effect of
      IL-6. The results demonstrate that IL-6, acting directly on peripheral organs
      and/or through the central nervous system (CNS) can alter the hormonal and
      carbohydrate milieu. We propose that these actions of IL-6 are one aspect of its
      role in the acute phase response.

PMID- 7628064
TI  - Pentoxifylline inhibits mediator synthesis in an equine in vitro whole blood
      model of endotoxemia.
AB  - Whole blood from 10 healthy horses was aseptically collected into heparin or
      citrate anticoagulant and incubated in vitro for 6 hr in the absence (saline
      control) or presence of 1 ng endotoxin/ml blood. Pentoxifylline (0.1, 1, 10, or
      100 micrograms/ml blood) was added 1 hr before, at the same time, or 1 hr after
      endotoxin. As compared to saline controls, pentoxifylline alone had no effect on
      mediator production, with the exception of significantly increasing 6
      ketoprostaglandin F1 alpha concentration. Pentoxifylline inhibited endotoxin
      induced increases in tumor necrosis factor (TNF) and interleukin-6 (IL-6)
      activity in a dose-related fashion, whether added before, at the same time, or
      after endotoxin. Pentoxifylline significantly inhibited tissue factor activity,
      but only when added before endotoxin. Pentoxifylline had no effect on endotoxin
      induced 6-keto-prostaglandin F1 alpha production, but significantly inhibited
      thromboxane B2 (TxB2) production. The results of this study indicate that
      pentoxifylline, at blood concentrations consistent with those achieved in vivo,
      has effects that may be beneficial in the treatment of endotoxemia.

PMID- 7628065
TI  - Study of septic shock in the non-human primate: relationship of
      pathophysiological response to therapy with anti-TNF antibody.
AB  - Therapy with anti-TNF antibody is reported to be effective in preventing
      morbidity and mortality in baboons given lethal infusions of Escherichia coli.
      Treated animals survived, and organ histopathology was absent when antibody was
      administered early after lethal infusions of E. coli. The present study explored
      the relationship between antibody dosage, pathophysiology, and survivability from
      shock. When antibody dose was decreased lungs, kidneys, adrenals, spleen, and
      liver were injured as shown by increased vascular congestion, hemorrhage, edema,
      and necrosis of tissues. Survival was also affected. All animals treated with 15
      mg/kg antibody survived as reported earlier; less than 60% survived with 7.5
      mg/kg; 9% survived with 5.0 mg/kg, and all died with 1.5 mg/kg. Serum
      concentrations of interleukin-6 (IL-6) increased markedly as dose of antibody
      decreased. The increases in concentrations of IL-6 were associated with increases
      in morbidity and mortality following E. coli administration.

PMID- 7628066
TI  - Beta-hexosaminidase: biosynthesis and processing of the normal enzyme, and
      identification of mutations causing Jewish Tay-Sachs disease.
AB  - OBJECTIVES: This report presents an overview of the nearly 100-year history of
      the study of Tay-Sachs disease in the Ashkenazi Jewish population. DESIGN AND
      METHODS: Each major step leading to our present understanding of the disease are
      highlighted. RESULTS: The original interest in the cause of this devastating
      disease in the late 1800s led to the identification of a novel glycolipid. GM2
      ganglioside, stored in the neurons of Tay-Sachs patients in the 1930s, and the
      elucidation of its structure in the 1960s. The identification of the defective
      isozyme, beta-hexosaminidase A, followed in 1968-69. Elucidation of the subunit
      structures of the hexosaminidase A (alpha beta) and B (beta beta) isozymes in
      1973 and their purification in 1974-80, led to the characterization of the
      biosynthesis, assembly, intracellular transport, and posttranslational processing
      of the two subunits in the 1980s. The ability to purify milligram quantities of
      the isozymes made possible the isolation of cDNA clones encoding both subunits in
      1985, and ultimately the identification of the causes of Jewish Tay-Sachs disease
      at the genomic DNA level in 1988. CONCLUSIONS: Tay-Sachs disease is the major
      model for lysosomal storage diseases. Similarly, the work done in the 1980s on
      hexosaminidase has been used as a model for understanding the cell biology of
      many other lysosomal proteins. Current research encompassing the fields of
      enzymology, cell biology, and molecular biology is linking genotypes with the
      clinical phenotypes of patients with Tay-Sachs and related diseases.

PMID- 7628067
TI  - Reactivity of creatinine with alkaline 3,5-dinitrobenzoate: a new fluorescent
      kidney function test.
AB  - OBJECTIVES: To develop a new quantitative fluorometric assay for creatinine with
      enhanced specificity and inherent fluorescence sensitivity. DESIGN AND METHODS:
      Creatinine is reacted with 3,5-dinitrobenzoate under alkaline reaction conditions
      to produce a fluorophore. Alternatively, 3,5-dinitrobenzoyl chloride or methyl
      3,5-dinitrobenzoate may be employed as reagents. Fluorophore development was
      evaluated for Group 1A bases under aqueous and mixed solvent conditions. RESULTS:
      The chemical reaction between creatinine and 3,5-dinitrobenzoate performed under
      highly alkaline conditions produced a fluorescent product with excitation and
      emission maxima near 410 and 475 nm, respectively. The reaction proceeds rapidly
      in the presence of group IA bases under both aqueous and mixed solvent
      conditions, in particular with water/dimethylsulfoxide and water/1,4-butanediol
      solvent systems containing 1.0 M LiOH. A linear calibration curve was obtained
      when the fluorescence intensity measured in microamperes was plotted versus
      creatinine concentration in the range of 5-50 mumol/L. The detection limit for
      creatinine was well below 1 mumol/L. CONCLUSIONS: A simple, sensitive and highly
      specific fluorometric method for the determination creatinine has been developed.

PMID- 7628068
TI  - Human bioassays to assess environmental genotoxicity: development of a DNA break
      bioassay in HepG2 cells.
AB  - OBJECTIVES: Increasing interest in environmental health issues has created a
      demand for improved methods for the assessment of pollutant effects on humans.
      Our laboratory has developed an in vitro assay for the quantification of
      genotoxicity, monitored as DNA single strand breaks (SSB), in the HepG2 human
      hepatoma cell line. DESIGN AND METHODS: This assay procedure, which is based upon
      alkaline unwinding and hydroxylapatite DNA chromatography, is both rapid and
      simple to perform. RESULTS: HepG2 cells responded to the standard mutagen, 4
      nitroquinoline N-oxide, demonstrating SSB formation at concentrations above 0.1
      mumol/L. Phenanthrene-9,10-quinone, a component of diesel exhaust, mediated SSB
      formation at concentrations above 250 nmol/L. Finally, an extract of contaminated
      sediment from the Great Lakes Basin mediated SSB formation in a dose-dependent
      manner. CONCLUSIONS: These results illustrate the utility of this human
      genotoxicity assay for future use in screening of environmental pollutants.

PMID- 7628069
TI  - A competitive chemiluminescent immunoassay for the sensitive measurement of
      apolipoprotein B100.
AB  - OBJECTIVES: We have developed a competitive chemiluminescent immunoassay for the
      sensitive measurement of apolipoprotein B100 (apoB) and conducted a preliminary
      evaluation of the method. DESIGN AND METHODS: In the assay, apoB-rabbit
      immunoglobulin G (IgG) conjugate competes with apoB in the sample for binding to
      acridinium N-hydroxysuccinimide labelled anti-apoB antibody. Goat anti-rabbit-IgG
      immobilized to magnetic particles is used to separate the apoB-rabbit IgG
      conjugate bound to the labelled anti-apoB antibody. Chemiluminescence, measured
      using a Ciba Corning Magic-Lite chemiluminometer, is inversely proportional to
      the concentration of apoB in the sample. RESULTS: The assay is completed in 1-2
      h. Within-run imprecision (n = 5) determined at 10, 100, and 200 micrograms/L of
      apoB was found to be 4.8%, 2.4%, and 3.5%, respectively. The between-run
      imprecision (n = 5) at the same concentrations of apoB was determined to be
      14.2%, 9.5%, and 7.7%, respectively. The proposed assay showed reasonable
      correlation (r = 0.86) with a commercially available immunoturbidimetric method.
      The lower limit of detection was 2.2 micrograms/L (4.0 pmol/L). CONCLUSIONS: This
      assay may be useful in tissue culture studies where sensitive measurement of
      secreted and intracellular concentrations of apoB are required. Our preliminary
      evaluation of the assay appears to confirm is usefulness.

PMID- 7628070
TI  - Regulation of apolipoprotein B biogenesis in human hepatocytes:
      posttranscriptional control mechanisms that determine the hepatic production of
      apolipoprotein B-containing lipoproteins.
AB  - OBJECTIVES: Hepatic overproduction of apolipoprotein B (apoB)-containing
      lipoproteins appears to be a common cause of hyperlipoproteinemia in humans.
      Patients with overproduction states secrete denser cholesterol ester-rich
      lipoprotein particles which are highly atherogenic. The formation of apoB
      particles involves a very complex process that requires the coordinated synthesis
      and assembly of apoB, triglycerides, cholesterol esters, phospholipids, and other
      components. ApoB expression is an important prerequisite for the assembly and
      secretion of apoB particles. Evidence to date appears to suggest that apoB
      expression is regulated posttranscriptionally. ApoB secretion rate is determined
      at the levels of apoB translocation into the endoplasmic reticulum (ER) as well
      as degradation within the ER. RESULTS AND HYPOTHESIS: Based on available data, we
      postulate that the rate of apoB particle secretion is determined at the critical
      point where newly-synthesized apoB interacts with core lipids, particularly
      triglycerides. The supply of these lipids determines the rate of translocation of
      the apoB molecule across the ER membrane and into the ER lumen. Lipidation of
      apoB facilitates its proper folding, its assembly into a lipoprotein particle,
      and its extracellular secretion. In the absence of lipids, apoB is misfolded
      resulting in the abortion of ER translocation and subsequent degradation by an
      apoB specific protease. CONCLUSIONS: The balance between intracellular
      degradation and extracellular secretion determines the rate at which the human
      liver secretes apoB particles.

PMID- 7628072
TI  - Whatever happened to PKU?
AB  - The history of PKU is one of science in the discovery of an inborn error of
      metabolism and a chemical cause of mental retardation; and also one of technology
      with the development of methods to prevent disease. PKU is the classic example of
      success in the prevention of a genetic disease. Meanwhile, the science has
      continued to evolve over the 60 years since the discovery of PKU, generating new
      understanding of its clinical and metabolic phenotypes and about phenylalanine
      hydroxylation. At least five known genes are involved in hydroxylation of
      phenylalanine, synthesis of tetrahybrobiopterin and regeneration of this
      cofactor. The genes have been cloned and mutations characterized for several
      enzymes (GTPCH, 6-PTPS, PHS/DoCH, DHPR, PAH). A new animal model (the enu mouse)
      is contributing to knowledge about pathogenesis of brain disease and potential
      new treatments. The human phenylalanine hydroxylase gene (PAH) itself harbors 99%
      of the mutations causing hyperphenylalaninemia, over 170 different mutations have
      been identified at this locus. They cause loss of function; none affecting
      regulation has been identified. The aggregate PKU gene frequency at 1% is
      polymorphic in many human populations and mutations are highly stratified by
      region and population reflecting a variety of mechanisms (founder effect, genetic
      drift, hypermutability and, perhaps, selection) for their occurrence and
      distribution.

PMID- 7628071
TI  - A protease assay using time-resolved lanthanide luminescence from an engineered
      calcium binding protein substrate.
AB  - OBJECTIVES: The objective of this work was to demonstrate the utility of
      luminescence from lanthanides bound to a mutant of the Ca2+ binding protein,
      oncomodulin, to monitor protease activity. DESIGN AND METHODS: A mutant of
      oncomodulin with a cysteine residue at position 57 located in the CD binding loop
      was conjugated to a salicylic acid group. The luminescence of Tb3+ resulting from
      electronic energy transfer from the salicylic acid group was monitored using time
      resolved lanthanide luminescence in the presence of proteolytic enzymes. RESULTS:
      Low detection limits for subtilisin (150 pg), chymotrypsin (2.5 ng), cathepsin B
      (3.5 ng), and HIV-1 protease (25 ng) were found. CONCLUSION: The simplicity of
      the assay coupled with its high level of sensitivity make it useful for the
      detection of protease at very low concentrations.

PMID- 7628073
TI  - Basic aspects of GABA-transaminase in neuropsychiatric disorders.
AB  - Over the last two decades, there have been several studies suggesting the major
      inhibitory amino acid neurotransmitter gamma-aminobutyric acid (GABA) is involved
      directly and/or indirectly in the pathogenesis of many neurologic diseases and
      psychiatric disorders. GABA is mainly degradated to succinic semialdehyde in a
      reaction catalyzed by the enzyme GABA-transaminase (GABA-T). Inhibition of this
      enzyme produces considerable elevation of GABA contents in the brain, and such
      elevation has been found to correlate with pharmacologic and behavioral effects.
      We focus attention, from the basic aspects, on brain and platelet GABA-T
      activities in various species, with a special reference to neuropsychiatric
      disorders. It seems that the activity of GABA-T in the brain and/or in the blood
      platelets is correlated to certain neuropsychiatric disorders such as alcoholism,
      epilepsy, and Alzheimer's disease. In animal and human studies, platelet GABA-T
      was identified with similar kinetic and inhibitor characteristics to those of the
      brain. Therefore, in this way, studies of the activity of the enzyme GABA-T in
      relation to neuropsychiatric disorders could be undertaken to understand,
      diagnose, and treat GABA-related disorders of the central nervous system.

PMID- 7628074
TI  - Measurement of homocyst(e)ine in the prediction of arteriosclerosis.
AB  - Homocyst(e)ine [H(e)], the sum of homocysteine, homocystine, and the homocysteine
      cysteine mixed disulfide, free and protein-bound, has been shown to be associated
      in retrospective case control studies, and in one prospective study, with
      vascular disease, including coronary artery disease (CAD), cerebrovascular
      disease, and peripheral vascular disease. Elevated levels of homocyst(e)ine
      severe enough to cause homocystinuria are seen in severe nutritional deficiencies
      of vitamin B12, folic acid and vitamin B6. Rare genetic disorders of vitamin B12
      synthesis of 5'-10'-methylene tetrahydrofolate reductase, or the pyridoxal
      phosphate-dependent enzyme cystathionine beta-synthase may cause severe
      hyperhomocyst(e)inemia and homocystinuria. The clinical manifestation of these
      disorders are mental retardation, neurological disorders, and widespread
      thromboembolic phenomena. The measurement of H(e) is currently performed using
      high-pressure liquid chromatography with fluorescence detection. Other methods,
      especially mass spectroscopy, are also used. Internal standards using increasing
      concentrations of homocystine and acetylcysteine and several external standards
      are used to ensure accuracy of the assay. Milder elevations of H(e) have recently
      been associated with vascular disease, in both men and women. The strength of
      this association appears to be stronger for peripheral and cerebrovascular
      disease than for CAD. Nevertheless, several case control studies in Europe,
      Canada, and the United States have shown that H(e) levels are elevated in CAD
      patients compared with controls, and H(e) levels are independent of the
      conventional cardiovascular risk factors (age, gender, lipid and lipoprotein
      cholesterol levels, hypertension, or cigarette smoking). One prospective study,
      the Physicians' Health Study, has shown that H(e) levels are slightly but
      significantly higher in CAD cases vs controls in a population of US
      physicians.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7628075
TI  - Relationship between red blood cell antioxidant enzymatic system status and
      lipoperoxidation during the acute phase of malaria.
AB  - OBJECTIVE: To investigate the relationship between oxidative stress and
      aggrevation of the disease in patients with malaria. METHODS AND RESULTS: In the
      present study lipoperoxidation was demonstrated during the acute phase of malaria
      by a significant decrease in polyunsaturated fatty acids (PUFA). The lowest
      values of PUFA were obtained for C20:4 and C22:6, which were the main targets of
      reactive oxygen species (ROS) when parasitemia was higher than 1%. Similarly,
      plasma vitamins E and A were significantly reduced during the acute phase of
      malaria owing to their consumption in part as antioxidants. However, evaluation
      of the antioxidant enzymatic system in red blood cells of malaria patients
      indicated no significant difference from controls. Only superoxide dismutase
      activity tended to decrease when parasitemia increased. CONCLUSION: The results
      suggest that superoxide radicals are the main ROS produced during the acute phase
      of malaria, and that rejuvenation of RBC during hemolysis involving increased
      enzyme activities interacts to protect RBC from excessive superoxide radical
      production.

PMID- 7628076
TI  - Evaluation of lipoprotein (a) [Lp (a)] as a risk factor for coronary artery
      disease in the Turkish population.
AB  - OBJECTIVE: Lipoprotein (a) [Lp (a)] is an atherogenic particle that structurally
      resembles a low-density lipoprotein (LDL) particle but contains a molecule of
      apolipoprotein (a) attached to apolipoprotein B-100 by a disulfide bond. Because
      of the fact that elevated plasma levels of Lp (a) have been shown to be an
      independent risk factor for coronary artery disease (CAD), we determined plasma
      Lp(a) levels in CAD for Turkish population, and compared them with previous
      findings of some developed countries. RESULTS: The mean plasma Lp (a) levels in
      CAD group (mean +/- SD; 0.41 +/- 0.21, g/L) was found approximately twofold
      higher than that of the control group (0.21 +/- 0.17 g/L). Also, it was found to
      be higher than the mean levels of CAD group in the other populations described in
      previous reports. But CAD prevalence in the Turkish population is lower than in
      those of developed countries, especially the United States. CONCLUSIONS: We
      concluded that the interaction between plasma Lp (a) levels and many other
      factors such as face and heredity affecting development of CAD may show different
      effects for development of CAD in each of those populations separately.

PMID- 7628077
TI  - 125I-RIA kit cannot distinguish vitamin D deficiency as well as a more specific
      assay for 25-hydroxyvitamin D.
AB  - OBJECTIVES: To compare a new radioimmunoassay (RIA), measuring vitamin D
      metabolites, against an established, competitive-protein binding assay (CPBA)
      that uses rat vitamin D binding protein. METHODS: For the CPBA, we first isolated
      25-hydroxyvitamin D (25(OH)D) by eluting sample through silica cartridges. For
      the RIA, serum was added to acetonitrile and centrifuged, followed by RIA using
      125I-25(OH)D3. RESULTS: The within-run CV was 1.5% to 4.1% by RIA, compared to
      8.1% to 15.0% by CPBA. For both methods, analytical recovery was not
      significantly different from 100%, and both methods were appropriately linear
      with sample dilution. We compared RIA values (y axis) from 90 subjects with
      25(OH)D ranging from 11 to 232 nmol/L by CPBA (x axis). The slope was 0.9992 (not
      significantly different from 1). However, the RIA exhibited a bias of 11.15
      nmol/L (p < 0.05 vs 0), and a correlation coefficient of r = 0.923. When the
      comparison was confined to the 37 samples in the lower half of our reference
      range, the RIA did not compare well: slope, 0.764 (p < 0.05 vs 1.0); intercept
      18.7 nmol/L (p < 0.05 vs 0); r = 0.517. For the samples below 36 nmol/L by CPBA,
      there was no discrimination by RIA between the 11 values below, and the 11 above
      the decision level (25 nmol/L by CPBA) for vitamin D deficiency. CONCLUSIONS: We
      conclude that the RIA is not optimized to detect vitamin D deficiency, and for
      this purpose it is not a valid substitute for conventional 25(OH)D methods.

PMID- 7628078
TI  - Evaluation of the Technicon Immuno I random access immunoassay analyzer and
      calculation of pediatric reference ranges for endocrine tests, T-uptake, and
      ferritin.
AB  - OBJECTIVES: Evaluation of the precision, accuracy, and user-friendliness of the
      Technician Immuno I. Calculation of pediatric reference ranges for ferritin and
      endocrine tests run on Immuno I. METHODS: Precision and accuracy were measured
      using controls and method comparison studies. Pediatric reference ranges were
      calculated by comparing the Immuno I results for 100 patients with those of the
      Abbott IMx and TDx. The regression equation obtained was then used to convert the
      IMx and TDx reference ranges to reference ranges for the Immuno I. RESULTS: The
      Immuno I provided both accurate and precise measurement of drugs and endocrine
      hormones. Pediatric reference ranges were obtained for ferritin and all endocrine
      tests. CONCLUSION: The Immuno I is user-friendly and provides reliable
      measurement of both the drugs tested and endocrine tests on a micro-sample.
      Reagent and curve stability are excellent.

PMID- 7628079
TI  - Evaluation of the i-STAT system: a portable chemistry analyzer for the
      measurement of sodium, potassium, chloride, urea, glucose, and hematocrit.
AB  - OBJECTIVE: To evaluate the analytical performance of the i-STAT system, which is
      designed for point of care testing and employs a hand-held chemistry analyzer and
      disposable cartridges, which in the configuration tested, are capable of
      measuring sodium, potassium, chloride, urea, glucose, and hematocrit in
      approximately 65 microL of blood in 90's. METHODS: Linearity and imprecision in
      hematocrit measurement were assessed using whole blood, while that for the other
      analytes were evaluated with aqueous solutions. The accuracy of the i-STAT system
      was judged by assay of patient specimens obtained both by venipuncture and
      fingerprick and correlated with the Kodak Ektachem 700XR and the microhematocrit
      methods. RESULTS: Linearity was obtained over the clinically relevant range for
      all analytes. Total imprecision as expressed by the coefficient of variation (CV)
      was less than 3.5% for all analytes at both high and low concentration except for
      a low concentration of urea where a CV of 9.4% was obtained. Linear regression
      analysis revealed minimal systematic errors. The standard error about the
      regression line (Sy/x) ranged from 0.017 for hematocrit to 2.262 for chloride in
      the assay of venous blood, whereas in the assay of capillary blood the Sy/x
      ranged from 0.018 for hematocrit to 0.755 for glucose. CONCLUSIONS: The
      analytical performance of the i-STAT was deemed acceptable by calculation of
      total error and comparison with published performance standards. Our study has
      shown the i-STAT system to be reliable, robust, and simple to operate. Moreover,
      the compactness of the analyzer and the requirement for only small volumes of
      whole blood will make it a valuable diagnostic tool in point of care settings.

PMID- 7628080
TI  - Correlation between plasma malondialdehyde and ceruloplasmin activity values in
      rheumatoid arthritis.

PMID- 7628081
TI  - Evolution of polymerase chain reaction to a quantitative laboratory tool.

PMID- 7628082
TI  - Apolipoprotein E: an important gene and protein to follow in laboratory medicine.
AB  - The human apolipoprotein (apo) E gene is polymorphic, with three common alleles
      (epsilon 2, epsilon 3, epsilon 4) coding for three isoforms (E2, E3, E4). The
      isoforms differ from each other by a single amino acid substitution, and also
      differ in their binding affinity for the four apo E receptors. Apo E polymorphism
      is an important determinant of risk for the development of cardiovascular and
      Alzheimer diseases, the prevalence of the epsilon 4 allele being increased in
      both kinds of patients compared with control subjects. Furthermore, the
      prevalence of the epsilon 4 allele differs among populations (range 5-40%,
      respectively, for Taiwanese and Papua New Guineans). Genotyping or phenotyping
      needs to be introduced in clinical laboratories. The choice of the method should
      be based on the types of patients who are examined. The apo E genotype is also a
      determinant of apo E plasma concentration. Standardization of apo E measurement
      is an important prerequisite before investigating the clinical interest of plasma
      apo E concentration. Determination of apo E genotype/phenotype and later the
      plasma concentration are expected to yield useful clinical laboratory
      information.

PMID- 7628083
TI  - Increased urinary excretion of analogs of Krebs cycle metabolites and arabinose
      in two brothers with autistic features.
AB  - A marked increase in analogs of Krebs cycle metabolites was found in the urine of
      two brothers with autistic features. These metabolites included citramalic,
      tartaric (3-OH-malic), and 3-oxoglutaric acids and compounds tentatively
      identified as a citric acid analog and partially identified as a phenylcarboxylic
      acid by the fragmentation pattern of the trimethylsilyl (TMS) derivatives of the
      compounds and mass shifts of the same compounds derivatized with perdeuterated
      N,O-bis(trimethylsilyl)trifluoroacetamide. The molecular mass of the TMS
      derivative of the tentatively identified citric acid analog was 596 Da, based on
      a finding of a significant M - 15 ion at m/z 581. The citric acid analog was
      excreted in quantities as high as 137 mmol/mol creatinine, based on the response
      factor of citric acid as a surrogate calibrator. A carbohydrate with a retention
      time and mass spectrum identical to arabinose was also found in high
      concentrations in the urine of these brothers.

PMID- 7628084
TI  - Detection of Charcot-Marie-Tooth type 1A duplication by the polymerase chain
      reaction.
AB  - Charcot-Marie-Tooth disease type 1A (CMT1A) is a hereditary peripheral neuropathy
      with a genetic locus on chromosome 17p11.2. The majority of patients carry a
      duplicated DNA segment that encompasses the gene PMP22, which encodes a
      peripheral myelin protein. PMP22 is the crucial gene involved in the pathogenesis
      of CMT1A. Molecular diagnosis of CMT1A requires detection of this duplicated
      segment. Existing methods for detection of the duplication are laborious and time
      consuming. We have developed a set of polymorphic (AC)n repeat markers (contained
      within the duplication) for use in the polymerase chain reaction, which give a
      high probability of detecting three unique alleles in affected individuals. This
      test detected 85% of a panel of 52 CMT1A patients in which the duplication had
      previously been demonstrated.

PMID- 7628085
TI  - Inborn errors of metabolism diagnosed in sudden death cases by acylcarnitine
      analysis of postmortem bile.
AB  - Fatty acid oxidation (FAO) disorders represent a frequently misdiagnosed group of
      inborn errors of metabolism. Some patients die at the first episode of fasting
      intolerance and, if appropriate investigations are not undertaken, often meet the
      criteria of sudden infant death syndrome (SIDS). To expand existing protocols for
      the postmortem diagnosis of FAO and other metabolic disorders, we tested the
      hypothesis that analysis for acylcarnitine in bile, a specimen readily available
      at autopsy, may be utilized for diagnostic purposes. Using electrospray/tandem
      mass spectrometry, we analyzed for acylcarnitine postmortem bile specimens from
      two infants with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency, one
      infant with glutaryl-CoA dehydrogenase deficiency, and 17 uninformative SIDS
      cases as controls. The affected cases, and none of the controls, showed marked
      accumulation of C10-C18 acylcarnitines or glutarylcarnitine (acyl/free carnitine
      ratio: 5.2, 2.7, and 1.9, respectively; controls 0.2 +/- 0.1). In one patient,
      all other diagnostic methods were uninformative, suggesting that bile
      acylcarnitine profiling could lead to identification of previously overlooked
      cases.

PMID- 7628086
TI  - Undercarboxylated osteocalcin and development of a method to determine vitamin K
      status.
AB  - We developed a RIA involving a polyclonal antibody against bovine osteocalcin,
      which has a carboxy-terminal epitope. Although the antibody recognizes both
      native and descarboxy osteocalcin, the two forms of osteocalcin were
      differentiated by adsorption to barium sulfate, taking advantage of the calcium
      binding properties of the vitamin K-dependent gla domain. To test the clinical
      application of undercarboxylated osteocalcin, we examined the effect of minidose
      warfarin on this measure in nine healthy subjects, ages 60 to 80 years. The
      percentage of undercarboxylated osteocalcin increased by 170% +/- 36% (mean +/-
      SE) after 7 days of treatment with warfarin, 1 mg/day. The effectiveness of
      undercarboxylated osteocalcin as a sensitive measure of vitamin K nutritional
      status was further established when concentrations dropped to 17% +/- 14% below
      baseline with 2 days of repletion with vitamin K1, 5 mg/day, during which
      prothrombin times did not leave the normal range.

PMID- 7628088
TI  - Immunometric assays of luteinizing hormone (LH): differences in recognition of
      plasma LH by anti-intact and beta-subunit-specific antibodies in various
      physiological and pathophysiological situations.
AB  - Restricted immunoreactivity of plasma luteinizing hormone (LH) has been described
      in some subjects when assayed with certain methods involving antibodies against
      intact LH. We have compared the performance of the Amerlite LH-30 (A) and Delfia
      LHSpec (D) assays (which include anti-intact and beta-specific antibodies,
      respectively) in normal and pathological conditions. As shown previously, results
      of the two systems were highly correlated with each other and, as we show here,
      with those of a bioassay. We found eight outliers (results outside the 95%
      confidence interval of the regression) among 427 samples studied from 121
      subjects. Of the outliers, five had Delfia results in a range (< 1 IU/L) that was
      associated with poor assay precision for that assay, and the ratios of their
      values by both methods (A:D ratios) were very low. This ratio was affected by
      endocrine status, e.g., was lower in postmenopausal women than in premenopausal
      controls, and varied intraindividually within the same menstrual cycle. The
      restricted immunoreactivity described previously for assays involving anti-intact
      LH antibodies may, in part, reflect these differences, which, in turn, may
      reflect the presence of isoforms (e.g., glycoforms) that are differentially
      recognized by assays that have different antibody configurations.

PMID- 7628087
TI  - Effect of hemodialysis on total antioxidant capacity and serum antioxidants in
      patients with chronic renal failure.
AB  - Cardiovascular disease is the major cause of mortality in patients receiving
      hemodialysis for chronic renal failure. Increased lipid peroxidation and
      depletion of chain-breaking antioxidants may contribute to increased risk of
      atherosclerosis. We have therefore assessed the effect of a single episode of
      hemodialysis on antioxidant status in 22 patients and control subjects. Overall,
      total antioxidant capacity of serum was increased in dialysis patients, but there
      was a marked reduction after hemodialysis [571 +/- 31 vs 342 +/- 22 mumol/L
      Trolox (water-soluble vitamin E analog) equivalents, P < 0.001]. The increase in
      total antioxidant capacity before hemodialysis was almost entirely due to
      relatively high serum urate. Among individual chain-breaking antioxidants,
      dialysis led to a decrease in urate (398 +/- 15 vs 136 +/- 12 mumol/L, P <
      0.001), ascorbate (10.5 +/- 1.7 vs 5.9 +/- 1.0 mumol/L, P < 0.01), and lipid
      corrected tocopherol (4.70 +/- 0.56 vs 4.26 +/- 0.39 mumol/mmol cholesterol, P <
      0.05). Protein thiol groups increased after dialysis (328 +/- 16 vs 422 +/- 22
      mumol/L, P < 0.001), whereas albumin remained unchanged (40.1 +/- 1.1 vs 41.0 +/-
      1.6 g/L, not significant). Although total antioxidant capacity of serum is
      increased in hemodialysis patients, depletion of key chain-breaking antioxidants
      may lead to accelerated atherogenesis.

PMID- 7628090
TI  - Characterization of a monoclonal antibody (HB-22) and development of an ELISA for
      human apolipoprotein A-I.
AB  - We describe the production and characterization of a high-affinity monoclonal
      antibody, HB-22, for apolipoprotein (apo) A-I, a major protein of human high
      density lipoproteins (HDL). Including Tween 20 in the reaction mixture increased
      the binding capacity of HB-22 to apo A-I. HB-22 showed monospecific reactivity
      with HDL or apo A-I, displaying no cross-reactivity with apo A-II, intermediate-,
      low-, or very-low-density lipoproteins. Immunoaffinity columns with HB-22 (in the
      absence of Tween 20) showed an immunosorbent capacity of 80 micrograms of apo A-I
      per milligram of antibody. The immunosorbent capacity of HB-22 for apo A-I was
      similar in plasma samples from normolipidemic, hypercholesterolemic, or
      hypertriglyceridemic patients. Comparative binding studies demonstrated that
      compared with other available monoclonal apo A-I antibodies, HB-22 had the
      greatest apparent affinity for binding to HDL. A competitive ELISA developed by
      utilizing HB-22 could detect as little as 20 ng of apo A-I in the reaction
      mixture. The intra- and interassay CVs of the ELISA were 5.4% and 9.5%,
      respectively.

PMID- 7628089
TI  - Assay of plasma testosterone during the first six months of life: importance of
      chromatographic purification of steroids.
AB  - Determination of the plasma concentration of testosterone (T) is important in
      evaluating infants born with ambiguous genitalia and micropenis, and several
      commercially available kits provide a direct assay of T in unextracted plasma.
      Using plasma samples obtained from 36 subjects < 6 months old, we compared the
      concentration of plasma T measured by RIA after extraction and purification by
      column chromatography with the T concentration measured in a direct assay. When
      aliquots of samples were purified before RIA, the concentration of T was markedly
      lower than in the direct assay. In the first 3 weeks postpartum, results of the
      direct assay were 3.8-fold greater than those obtained after purification. This
      difference decreased over time, and by age 2 months there was fairly good
      agreement between the two methods. These data indicate that some direct assays of
      plasma T are inappropriate during the first 2 months postpartum.

PMID- 7628091
TI  - Sensitive method for analysis of strontium in human and animal plasma by graphite
      furnace atomic absorption spectrophotometry.
AB  - For long-term pharmacokinetic studies in humans as well as in experimental
      animals, an analysis of strontium (Sr) with a low detection limit and high
      sensitivity is necessary. The data presented here describe the optimization of
      the furnace program and sample handling for measuring Sr in plasma by using
      graphite furnace atomic absorption spectrophotometry. The method was validated
      and applied to studies on the pharmacokinetics of SrCl2 in humans and rats.
      Calibration curves were linear up to 57.1 nmol/L. The limit of detection and
      lower limit of quantification were 0.21 and 0.57 nmol/L, respectively. Reciprocal
      sensitivity was 0.53 nmol/L Sr at A = 0.0044. The intraassay precision was 2.2%,
      1.5%, and 1.1% (n = 6) at 4.57, 22.7, and 49.2 nmol/L Sr, respectively. At these
      concentrations, the interassay precision and recovery were 0.7%, 1.5%, and 1.8%
      and 100.4%, 99.1%, and 100.6% (n = 12), respectively. The endogenous Sr
      concentration in human plasma samples was 0.27 +/- 0.07 mumol/L (n = 18).
      Pharmacokinetic studies in a human volunteer and in rats demonstrated that this
      procedure was suited for measuring low Sr concentrations and was applicable to
      small sample volumes.

PMID- 7628092
TI  - Fully automated assay for cobalamin-dependent methylmalonyl CoA mutase.
AB  - We constructed a fully automated assay for the cobalamin-dependent enzyme
      methylmalonyl coenzyme A (CoA) mutase. The assay involves preincubation of the
      enzyme with adenosylcobalamin, incubation with substrate, termination of the
      reaction by adding trichloroacetic acid, filtration to remove precipitated
      protein, and finally analysis of the filtrate (containing methylmalonyl CoA and
      the product succinyl CoA) by HPLC. These steps were carried out by an inexpensive
      programmable autosampler equipped with thermostated sample racks and mobile
      disposable extraction column racks used here as a sample filtering device. A
      central element in the developmental work was to measure stability of reagents,
      enzyme, and product against the storage conditions during unattended analysis and
      the time table of the program. We evaluated the performance of the method by
      measuring methylmalonyl CoA mutase activity in rat liver, human fibroblasts, and
      human glioma cells. The within-run imprecisions (CV) were 2-10% for measuring
      enzyme activity in 20 replicate samples of a homogenate (test of the automated
      assay), and 7-12% for measuring enzyme activity in homogenates from 20 culture
      dishes (test of the total procedure). The method allows the unattended analysis
      of 56 samples per 24 h. This strategy for automation may be easily adapted for
      other enzyme assays.

PMID- 7628093
TI  - Interpretation of serial measurements of international normalized ratio for
      prothrombin times in monitoring oral anticoagulant therapy.
AB  - Despite careful monitoring of oral anticoagulant treatment (OAT), some
      international normalized ratio (INR) for prothrombin time values will fall
      outside the therapeutic range. Considerable changes in serial INR results from
      OAT patients may be caused by random fluctuation alone, and, for statistical
      reasons, a fraction of the INR values will fall outside therapeutic range and
      interfere with dose adjustments. On the basis of therapeutic intervals and
      statistical evaluation of reference changes, we suggest and discuss an
      alternative method for interpretation of serial INR measurements. Retrospective
      evaluation of serial measurements of INR from OAT patients revealed an
      "overshooting" phenomenon. When a dose was adjusted on the basis of insignificant
      change in INR value, the subsequent INR value generally fell in the opposite
      direction. If a further change of dose was initiated because of the new INR
      value, a similar course in the opposite direction was observed. This "ping-pong"
      effect renders patients in a fluctuating state of anticoagulation and may
      introduce increased risk of complications. The suggested method provides an
      objective criterion for dose adjustments in OAT, which should reduce patients'
      risk.

PMID- 7628094
TI  - Spectrophotometric determination of ascorbic acid and dehydroascorbic acid.
AB  - We present a method for measuring ascorbic acid in methanol/trichloroacetic acid
      extracts prepared from human plasma after enzymatic oxidation of ascorbic acid to
      dehydroascorbic acid by ascorbate oxidase. Samples were assayed by
      spectrophotometrically monitoring the kinetics of the concentration-dependent
      absorbance changes of dehydroascorbic acid with phosphate-citrate-methanol
      buffers. Ascorbic acid was determined as the difference between dehydroascorbic
      acid and total ascorbic acid content. The detection limit was < 0.5 mumol/L. The
      calibration curve was linear (r > 0.995) over the range 0-1000 mumol/L.
      Analytical recovery of ascorbic acid added to plasma was 93-105%. The between-day
      variance was < 7%. Comparison of the spectrophotometric determination (y) with a
      chromatographic procedure (x) gave y = 1.02x - 0.653 (Sylx = 3.61) over the range
      of physiologically relevant concentrations. Total analysis time is < 10 min per
      sample and allows the simultaneous analysis of multiple samples.

PMID- 7628095
TI  - Serial lecithin/sphingomyelin ratios and surfactant/albumin ratios in tracheal
      aspirates from term infants with respiratory failure receiving extracorporeal
      membrane oxygenation.
AB  - Serial tracheal aspirate samples were obtained for determination of
      lecithin/sphingomyelin (L/S) ratios from 47 term infants in respiratory failure.
      Phospholipids were extracted with Folch solution (chloroform:methanol, 2:1 by
      vol) and analyzed by HPLC with use of silica column and a mobile phase of
      acetonitrile:methanol:water (48:31:21, by vol). Surfactant/albumin (S/A) ratios
      were determined with the TDx Fetal Lung Maturity Assay (Abbott Labs). L/S ratios
      increased significantly over time in all patients (F = 19.42, P < 0.0001). The
      S/A ratio correlated with the L/S ratio (r = 0.554, P < 0.001). This study
      suggests that postnatal surfactant deficiency in term newborns with respiratory
      failure is a component of the newborn's lung injury.

PMID- 7628096
TI  - Interleukin-6 as a first-look indicator of acute myocardial infarction.

PMID- 7628097
TI  - Effect of smoking on plasma ferritin concentrations in pregnant women.

PMID- 7628098
TI  - Rapid detection of ALDH2 genotypes by constant denaturant gel electrophoresis.

PMID- 7628099
TI  - Small-group, case-based clinical biochemistry course for a medical laboratory
      science curriculum.

PMID- 7628100
TI  - Effect of light and gamma-irradiation on pyridinolines and telopeptides of type I
      collagen in urine.

PMID- 7628101
TI  - Early serum cardiac troponin I and T concentrations after successful thrombolysis
      for acute myocardial infarction.

PMID- 7628102
TI  - Stability of thalidomide in human plasma.

PMID- 7628103
TI  - Underestimation of serum iron with automated methods.

PMID- 7628104
TI  - Early biochemical evidence of neoplasm in a case of ascites of unknown origin.

PMID- 7628105
TI  - To e or not to e?

PMID- 7628106
TI  - A modest proposal for the consistent presentation of ROC plots in Clinical
      Chemistry.

PMID- 7628108
TI  - Pursuing Medical Relevance: A Crucial Role for the Clinical Laboratory Scientist-
      From a Focus on Analytical Performance to One on Medical Outcome. Proceedings of
      the 18th annual Arnold O. Beckman Conference on Clinical Chemistry. Charleston,
      South Carolina, February 5-6, 1995.

PMID- 7628107
TI  - Adjustment of total calcium with results for BCP albumin.

PMID- 7628109
TI  - The changing role of the clinical laboratory scientist: coming out of the
      basement.
AB  - The position of clinical chemistry within the discipline of laboratory medicine
      is firmly established. As a result, pathologists, chemists, and scientists have
      been attracted to an emerging field full of promise and expectations. For most,
      the expectations of a rewarding career and growth of the discipline have been
      met. However, in a climate where factors such as "capitation" and "managed care"
      influence every facet of healthcare, many are reviewing their expectations and
      wondering whether the 21st century will bring the same promise enjoyed by the
      pioneers in the 20th century. In the future, laboratory scientists must align
      their expectations to the demands for new technologies, medical practices, and
      healthcare systems that will require justification for all activities, expense,
      and personnel. To succeed in this new environment, the clinical chemist will need
      excellent managerial skills, an understanding of how to articulate the benefits
      of technologies and laboratory tests, and a willingness to embark on a career of
      unceasing education.

PMID- 7628110
TI  - A model for medical decision making and problem solving.
AB  - Clinicians confront the classical problem of decision making under uncertainty,
      but a universal procedure by which they deal with this situation, both in
      diagnosis and therapy, can be defined. This consists in the choice of a specific
      course of action from available alternatives so as to reduce uncertainty. Formal
      analysis evidences that the expected value of this process depends on the a
      priori probabilities confronted, the discriminatory power of the action chosen,
      and the values and costs associated with possible outcomes. Clinical problem
      solving represents the construction of a systematic strategy from multiple
      decisional building blocks. Depending on the level of uncertainty the physicians
      attach to their working hypothesis, they can choose among at least four prototype
      strategies: pattern recognition, the hypothetico-deductive process, arborization,
      and exhaustion. However, the resolution of real-life problems can involve a
      combination of these game plans. Formal analysis of each strategy permits
      definition of its appropriate a priori probabilities, action characteristics, and
      cost implications.

PMID- 7628111
TI  - Probable impact of the 1994 elections on laboratory medicine.
AB  - During the past quarter century, federal health policy makers concerned
      themselves with: (a) improving the quality of healthcare delivered to the
      American public; (b) increasing access to needed healthcare services; and (c)
      curtailing the escalating cost of such services. These goals led Congress to
      expand the role of the federal government in regulating the delivery of
      healthcare. The enactment of the Clinical Laboratory Improvement Amendments of
      1988 (CLIA '88) was a significant and widely discussed example of how Congress,
      when controlled by the Democrats, sought to correct healthcare problems and
      achieve federal objectives. In November 1994, the Republicans won majorities in
      both the Senate and the House, promising to reduce the federal government's
      power. Many now believe that CLIA '88, or significant parts of it, could be
      substantially modified as part of this effort. This paper addresses the
      developments that led the Democrats to seek enactment of CLIA '88 and the likely
      arguments that may be offered by the Republicans to lessen the rigor and scope of
      the law.

PMID- 7628112
TI  - Metaanalysis in clinical chemistry: validation of cardiac troponin T as a marker
      for ischemic heart diseases.
AB  - Metaanalysis is a method that incorporates the pooling of previously published
      results to produce more statistically significant results. We used metaanalysis
      to examine the role of a new cardiac marker, cardiac troponin T (cTnT), in
      patients with ischemic heart disease. Metaanalysis of six articles and one
      abstract on cTnT showed that this marker was just as sensitive as creatine kinase
      MB isoenzyme (CK-MB) for the retrospective diagnosis of acute myocardial
      infarction (AMI) 12-48 h after onset but less specific. Most of these articles
      showed that cTnT was increased in non-AMI patients with unstable angina pectoris.
      In a metaanalysis of four papers, two abstracts, a letter, and an unpublished
      manuscript, we examined the prognostic role of cTnT in non-AMI cardiac patients.
      For an unfavorable endpoint defined as cardiac death, AMI, or the need for
      coronary artery revascularization, the results demonstrated that abnormal
      concentrations of cTnT were associated with a higher risk for a poor outcome than
      were normal concentrations of cTnT. We also compared cTnT with CK-MB for risk
      stratification. Metaanalysis will become an increasingly important tool for
      evaluating new tests as they become available.

PMID- 7628113
TI  - Role of clinical practice guidelines and clinical profiling in facilitating
      optimal laboratory use.
AB  - Many studies have demonstrated the potential benefits of clinical practice
      guidelines in improving clinical practice. Moreover, several different kinds of
      clinical profiles have been developed to address issues related to quality,
      utilization, and outcomes of specific healthcare practices. With this expanded
      use of clinical practice guidelines and clinical profiles, clinical laboratory
      specialists have an opportunity to play an influential leadership role.

PMID- 7628114
TI  - Clinical laboratory consultation.
AB  - The future of healthcare delivery systems will depend on their ability to provide
      the best care at the least cost. In the clinical laboratory, this translates to
      ensuring that decreased test use means appropriate use. The latter is unlikely to
      occur unless clinical laboratories provide practicing physicians with advice on
      test strategy and interpretation of results. Effective clinical laboratory
      consultation requires an identification with clinical problems. Important
      components of the identification process are an appreciation of the probabilistic
      rather than deterministic nature of the relation of clinical and laboratory data
      to disease and the inevitable tradeoff between false negatives and false
      positives that clinical circumstances demand. Institution of consultation
      services requires that the clinical laboratory adopt a proactive approach to
      advocating test strategy and interpreting results. Consultation on test strategy
      is likely to be facilitated by further developments in practice guidelines and by
      advances in informatics and telemedicine.

PMID- 7628115
TI  - Multivariate receiver-operating characteristic curve analysis: prostate cancer
      screening as an example.
AB  - The evolution of test performance analysis should include the long-term costs and
      benefits associated with testing. Evolutionary laboratory techniques to achieve
      this include introduction of a new methodological technique, a multivariate
      extension to a current analytical technique, receiver-operating characteristic
      (ROC) curve analysis (MultiROC analysis). This extension to ROC methodology
      allows the comparison of composite test rules in a format similar to that of ROC
      curves. Statistical properties, guidelines for use, and a detailed example are
      described. MultiROC is used in the outcomes analysis of the value of screening
      for prostate cancer. The effect of age and different test decision thresholds are
      examined in an extension of a previously published outcomes analysis. The results
      indicate that the variations in test performances caused by these components are
      important in assigning a final cost:benefit ratio of screening for prostate
      cancer.

PMID- 7628116
TI  - Value-added laboratory medicine in an era of managed care.
AB  - Clinical laboratory consultants (M.D.s and Ph.D.s) must add value and medical
      relevance to the healthcare system to earn and maintain their roles in an era of
      managed care. Service opportunities include new and expanded roles in system-wide
      (a) managing of point-of-care testing, (b) informatics and information systems,
      (c) clinical consultation, (d) resource management, (e) management of
      utilization, (f) improving healthcare quality assurance, and (g) technology
      assessment and implementation. Hypothesis-driven research focused on the linkage
      between the laboratory and outcome analysis, clinical practice guidelines, total
      quality improvement, technology assessment, and healthcare policy provides major
      opportunities to complete for expanding research support. Changes in clinical
      laboratory consultant training are necessary to provide the knowledge, skills,
      and experience required to provide value-added and medically relevant services.
      Clinical laboratory consultants with Ph.D. degrees should initially be trained
      broadly in all areas of the laboratory, with emphasis on system-wide issues, and
      then trained as specialized scientists.

PMID- 7628117
TI  - Variable expression of the popliteal pterygium syndrome in two 3-generation
      families.
AB  - Three successive generations in two families affected with the popliteal
      pterygium syndrome are reported. While expression of the syndrome was relatively
      mild in the first and second generation, the patients in the third generation
      showed the full-blown syndrome. Differential diagnosis between mildly affected
      patients with the popliteal pterygium syndrome and those with Van der Woude
      syndrome is difficult and may even be impossible. The present observations
      further support the hypothesis that both syndromes may in fact represent variants
      of the same condition.

PMID- 7628118
TI  - Triosephosphate isomerase deficiency: biochemical and molecular genetic analysis
      for prenatal diagnosis.
AB  - Inherited deficiency of the glycolytic enzyme triosephosphate isomerase leads to
      a multisystem disorder characterized by progressive neuromuscular dysfunction,
      chronic nonspherocytic hemolytic anemia and increased susceptibility to severe
      infections. Most patients die within the first 6 years. We examined a family with
      severe triosephosphate isomerase deficiency. The 1-year-old index patient
      suffered from hemolytic anemia, neuromuscular impairment and pneumonias, with the
      necessity of intermitten mechanical ventilation. Triosephosphate isomerase
      activity in erythrocytes was reduced to about 20% of normal. Heat stability of
      the enzyme was strongly reduced; concentration of the physiological substrate,
      dihydroxyacetone phosphate was increased 20-fold due to the metabolic block.
      Direct sequencing of the triosephosphate isomerase gene revealed homozygosity for
      the formerly described GAG-->GAC-mutation changing 104 Glu-->Asp. During a 2nd
      pregnancy we examined a cord blood sample obtained in the 19th gestational week.
      The biochemical data on enzyme activity, heat stability of the enzyme and
      concentration of dihydroxyacetone phosphate were in the normal range. The
      molecular genetic analysis confirmed the presence of the normal triosephosphate
      isomerase alleles. Pregnancy was continued, resulting in the delivery of an
      unaffected, healthy newborn.

PMID- 7628119
TI  - Familial hypertryptophanemia in two siblings.
AB  - Mild and moderate mental retardation with exaggerated affective responses,
      periodic mood swings, and apparent hypersexual behavior were present in two
      siblings with hypertryptophanemia and tryptophanuria. In addition, the male had
      severe myopia, a speech impediment, musculoskeletal abnormalities and perceptual
      hypersensitivity. His sister was deaf, which was ascribed to antenatal rubella.
      The occurrence in siblings and the presence of abnormal urinary tryptophan
      metabolite in the mother and a half-sibling suggest that the condition results
      from an autosomal recessive gene with minor expression in some heterozygotes.

PMID- 7628120
TI  - Restriction fragment length polymorphisms at the apoprotein genes AI, CIII and B
      100 and in the 5' flanking region of the insulin gene as possible markers of
      coronary heart disease.
AB  - Several sequence variations were examined for being endogenous "risk markers" in
      the development of CHD. The "markers" in this study included: the PstI-SstI RFLPs
      in the apo AI-CIII gene cluster, the EcoRI-MspI RFLPs in the apo B100 gene and
      the SstI RFLP in the 5' flanking region of the insulin gene. The study population
      comprised 700 individuals of German origin. A strong association of these
      "markers" to the disease phenotype predicts their loss in healthy individuals
      with ages above that of the prevalent incidence of CHD. In contrast, these
      "markers" should accumulate in diseased persons. A significant age-dependent
      selection was observed for the EcoRI RFLP in the apo B100 gene. This was the case
      when the allele and genotype frequencies of healthy old individuals were compared
      with those of newborns. In contrast, no RFLP showed significant differences in
      allele and genotype distributions between patients defined by coronary
      angiography and controls. In the group of patients, but not controls, several
      RFLP genotypes were found to be associated with significantly higher serum levels
      of cholesterol and triglycerides. This was true in the case of serum cholesterol
      comparing the genotypes S1S2 with those of S1S1 (p = 0.05) observed for the SstI
      polymorphic site in the 3' noncoding region of the apo CIII gene. Significantly
      higher levels of triglycerides were found within the heterozygous patients P1P2
      (p = 0.045) and S1S2 (p = 0.02) than in the homozygotes P1P1 and S1S1 for the
      PstI-SstI RFLPs at the apo AI-CIII gene cluster.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7628121
TI  - Inter- and intrafamilial variability in mucolipidosis II (I-cell disease).
AB  - In this paper nine patients with mucolipidosis II (I-cell disease) are described.
      They had clinical features commonly found in mucolipidosis II, including
      disproportionate dwarfism, coarse facial features and mental retardation.
      However, there was remarkable variability in age of onset, organ manifestation
      and radiological findings. Some had unusual clinical symptoms including
      pericardial effusion and profound brain atrophy. Striking differences in
      phenotypic expression were also seen in two affected siblings. Clinical
      heterogeneity is observed not only in mucolipidosis II but also in many other
      lysosomal storage disorders. The factors that may contribute to this clinical
      diversity are discussed.

PMID- 7628122
TI  - Skin color and cancer mortality among black men in the Charleston Heart Study.
AB  - The association between skin color and 30-year cancer mortality in a random
      sample of black men and a peer-nominated group of high socioeconomic status (SES)
      black men was evaluated in the Charleston Heart Study, a prospective study, begun
      in 1960, designed to investigate the epidemiology of coronary heart disease in a
      biracial cohort. Skin color was used as a continuous variable and as a
      categorical variable, by tertiles, in a Cox proportional hazards regression
      model. In the high SES group, there was a statistically significant decreasing
      relationship between skin color and cancer mortality, with those having the
      lightest skin having the lowest cancer mortality. In the random sample of black
      men, the relationship between skin color and cancer mortality was not
      statistically significant; however, the data indicated a slight protective effect
      among those with the lightest skin color. Because degree of skin reflectance is a
      measure of black-white admixture, these results may indicate a genetic mechanism
      underlying the differences in cancer mortality across skin color groups. Skin
      color is also recognized as a marker for psychosocial factors. Therefore, poor
      prognosis among those with darker skin color as a result of failure of early
      detection, inadequate treatment, and a variety of psychosocial stressors
      represents an alternative explanation of the study findings.

PMID- 7628124
TI  - Acro-pectoro-renal field defect with contralateral ureteropelvic junction
      obstruction.
AB  - Ureteropelvic junction obstruction was noted in a newborn male infant with acro
      pectoro-renal field defect. To our knowledge, this association has not previously
      been reported. Ultrasonography of the urinary tract should be performed on all
      children with aplasia of the pectoralis major muscle.

PMID- 7628123
TI  - Periumbilical skin length measurements in the newborn.
AB  - Normal limits of periumbilical skin were determined in 304 newborn babies in the
      first 24 h. Cranial umbilical skin (SD) was 12.36 (3.23) mm and caudal umbilical
      skin (SD) was 8.76 (3.10) mm on the average. It is recommended that cranial
      umbilical skin measurement should be included in the examination of dysmorphic
      neonates, and those with cranial skin length above 18.82 mm (> 2 SD) should be
      carefully evaluated for Rieger syndrome.

PMID- 7628125
TI  - New familial association between ocular coloboma and loose anagen syndrome.
AB  - We present two cases of loose anagen syndrome associated with ocular coloboma in
      two siblings of unaffected parents and with no family history. We believe they
      represent a new familial association between these two conditions.

PMID- 7628126
TI  - Symptomatic heterozygosity in the Ellis-van Creveld syndrome?
AB  - A 13-month-old girl with Ellis-van Creveld syndrome and her mildly affected
      father are described. We discuss whether the father is a symptomatic heterozygote
      of the Ellis-van Creveld syndrome or an untypical affected patient with Weyers'
      acrodental dysostosis.

PMID- 7628127
TI  - Amyloid disease of the heart.

PMID- 7628128
TI  - Management of myocardial infarction patients with an occluded infarct-related
      artery: additional commentary.
AB  - The evidence is becoming stronger (but not conclusive) that restoration of flow
      in the infarct-related artery at a later date than is generally accepted might
      decrease mortality. The CORAMI report suggests a good outcome with rescue
      angioplasty, but, unfortunately, there was no control group. Since urgent rescue
      PTCA opened the infarct-related artery in the 29% of patients who remained
      occluded after thrombolysis, those cardiologists advocating emergency PTCA in all
      infarcting patients argue that 100% of occluded vessels can be opened with PTCA.
      I don't argue that fact but would point out that 71% of these same patients would
      have had unnecessary angioplasty since the occluded artery would have opened with
      thrombolytic therapy. The randomized trial performed by Ellis and colleagues was
      a difficult one because of physician bias. It took three years to complete at 20
      sites, and in the presence of an occluded anterior descending coronary artery
      some investigators were reluctant to randomize all of their patients to
      conservative therapy. Obviously, a large trial would be appropriate to confirm
      Ellis and colleagues' observations but I doubt this will ever be done. Based on
      what is now known, I think it is worthwhile to consider rescue angioplasty in
      patients with a known occluded infarct-related artery. Unfortunately, that means
      performing coronary angiography almost immediately in all patients with
      infarcting myocardium in order to identify those with persistant occlusion.

PMID- 7628129
TI  - Clinical applications of body surface potential mapping.
AB  - Accumulated evidence suggests that the electrocardiographic information provided
      by the standard 12-lead electrocardiogram can be improved by use of multilead
      electrocardiograms. The clinical utility of body surface potential mapping is
      related to the selective regional information provided by the increased number of
      leads. That clinical utility includes such things as improved localization of
      accessory pathways in preexcitation syndromes, improved localization of pacing
      sites within the ventricles, localization of late potentials, and improved
      recognition of acute myocardial ischemia. Recording equipment and interpretation
      schemes are available to make possible more widespread application of potential
      mapping.

PMID- 7628130
TI  - Dobutamine stress echocardiography for the diagnosis and management of coronary
      artery disease.
AB  - Infusion of dobutamine in low and high doses in combination with echocardiography
      can be used for the assessment of myocardial viability and functional
      significance of coronary artery disease. Improvement of contractile function of
      hypokinetic or akinetic ventricular wall segment with low-dose dobutamine has a
      high predictive value for the detection of hibernating and stunned myocardium.
      High-dose dobutamine stress is of value for noninvasive diagnosis of coronary
      disease, assessment of its clinical significance, risk stratification of patients
      after myocardial infarction, preoperative evaluation of patients undergoing major
      noncardiac surgery, and assessment of the efficacy of coronary revascularization.
      It has an excellent safety record even in the immediate postmyocardial infarction
      period.

PMID- 7628131
TI  - Effect of simvastatin on Lp(a) concentrations.
AB  - The effect of HMG-CoA reductase inhibitors on Lp(a) concentrations is
      controversial, with some studies showing an increase and others showing no effect
      on Lp(a) concentrations. Many of these studies have been limited by small sample
      size and the lack of a prospective design. We evaluated the effect of four
      treatments: (1) placebo, (2) simvastatin 10 mg PO QPM, (3) simvastatin 20 mg PO
      QAM, and (4) simvastatin 20 mg PO QPM on Lp(a) concentrations in a prospective,
      randomized, controlled clinical trial of 24 weeks in 343 subjects in 28 clinical
      sites in the United States. Simvastatin was not associated with a change in Lp(a)
      concentrations relative to placebo. These results were not affected by
      controlling for race, initial Lp(a) level, or urinary albumin excretion.
      Simvastatin significantly reduced low-density lipoprotein (LDL) cholesterol
      levels (10 mg PO QPM: -27.6%; 20 mg PO QAM: -28.1%; and 20 mg PO QPM: -34.3%, all
      p < 0.001). It was concluded that in a large, randomized, controlled trial,
      simvastatin does not affect Lp(a) levels but markedly lowers LDL cholesterol
      levels.

PMID- 7628133
TI  - Initial depolarizing potentials in Wolff-Parkinson-White syndrome using signal
      averaged electrocardiograms: correlation with reciprocating tachycardia.
AB  - Initial depolarizing potentials were examined in patients with Wolff-Parkinson
      White (WPW) syndrome using signal-averaging techniques. In all, 25 WPW patients
      and 21 age-matched healthy children were studied. Ten of the patients were
      symptomatic and 15 were asymptomatic. Symptomatic patients with supraventricular
      tachycardias had longer durations of low-amplitude signals (LAS) < 40 mu V in the
      initial portion of the QRS complex (initial LAS, 49 +/- 7 ms vs. 37 +/- 9 ms, p <
      0.01) and lower root-mean-square (RMS) voltage in the initial 40 ms of the QRS
      complex (initial RMS, 12 +/- 4 mu V vs. 23 +/- 8 mu V, p < 0.01) compared with
      asymptomatic patients. When a symptomatic patient was defined as having an
      initial LAS of > 46 ms or an initial RMS of < 15 mu V, the sensitivity and
      specificity for predicting documented supraventricular tachycardia were 100 and
      67%, respectively. These SA-ECG findings may reflect instability of conduction in
      symptomatic patients through an accessory pathway and may identify those at high
      risk for supraventricular tachycardia.

PMID- 7628132
TI  - High-density lipoprotein cholesterol level and smoking modify the prognosis of
      patients with coronary vasospasm.
AB  - A cardiovascular event analysis was performed in a subset of 80 consecutive
      patients with vasospastic coronary artery disease. During the follow-up period
      (30 +/- 2 months, mean +/- SD), 9 patients had vascular accidents, including
      acute myocardial infarction, unstable angina, and stroke (Group A), while the
      remaining 71 patients were eventfree (Group B). Serum total-cholesterol, low
      density lipoprotein cholesterol, and triglyceride levels were not different
      between the two groups at the baseline as well as after follow-up. However, the
      HDL-C level at baseline was significantly lower in Group A (33.5 +/- 2.6 mg/dl)
      than in Group B (41.9 +/- 1.7 mg/dl, p < 0.05). The HDL-C level increased
      significantly during the follow-up in Group B (delta HDL-C: 6.2 +/- 1.2 mg/dl, p
      < 0.01), but not in Group A (delta HDL-C: -3.2 +/- 2.7 mg/dl). The HDL-C level
      after follow-up was significantly lower in Group A (30.3 +/- 2.9 mg/dl) than in
      Group B (48.1 +/- 1.5 mg/dl, p < 0.01). Current smokers at the end of the follow
      up period were more prevalent in Group A (67%) than in Group B (11%, p < 0.01).
      Cardiovascular accidents occurred more often in current smokers (6/14, 43%) at
      the end of the follow-up than in current nonsmokers, including quitters (3/66,
      5%; p < 0.05). The HDL-C level was increased significantly (delta HDL: 6.2 +/-
      1.3 mg/dl, p < 0.01) in the latter patients, but not in the former (delta HDL: 
      0.4 +/- 2.9 mg/dl).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7628135
TI  - Transesophageal echocardiography in the evaluation of cardiac myxoma: a case of
      familial myxoma.
AB  - The vast majority of atrial myxomas are readily apparent on standard
      transthoracic echocardiography. We present the case of a young woman with known
      history of familial myxoma, in whom a large left atrial mass was identified on
      transthoracic echocardiography. Transesophageal study more clearly delineated the
      extent and origin of the tumor. In addition, an unsuspected tumor in the right
      ventricle was also identified. These findings were confirmed at surgery, and both
      masses were excised. The advantages of transesophageal echocardiography in
      evaluation and management of this unusual subset of patients with cardiac tumor
      are discussed.

PMID- 7628134
TI  - Myocardial dysfunction and abnormal left ventricular exercise response in
      autonomic diabetic patients.
AB  - In diabetic patients, the pathophysiologic mechanisms of exercise-induced left
      ventricular (LV) dysfunction remain controversial. In this study, the role of
      myocardial contractility recruitment in determining an abnormal LV response to
      isometric or dynamic exercise has been investigated in 14 diabetic patients with
      autonomic dysfunction. Ischemic heart disease was excluded by the absence of LV
      wall motion abnormalities induced by isotonic and isometric exercise and by
      coronary angiography. Left ventricular and myocardial function were studied at
      rest, and during isometric and isotonic exercise, by two-dimensional
      echocardiography; moreover, recruitment of an inotropic reserve was assessed by
      postextrasystolic potentiation at rest and at peak handgrip. An abnormal response
      of LV ejection fraction to isometric (9/14) or to dynamic (8/14) exercise was
      frequent in study patients. In these patients, baseline myocardial contractility
      was normal, and the significant increase in ejection fraction by
      postextrasystolic potentiation indicated a normal contractile reserve (65 +/- 7%
      vs. 74 +/- 6%, p = 0.001). Nevertheless, the downward displacement of LV ejection
      fraction-systolic wall stress relationships during exercise suggests an
      inadequate increase in myocardial contractility. However, the abnormal ejection
      fraction at peak handgrip was completely reversed by postextrasystolic
      potentiation (67 +/- 6% vs. 58.1 +/- 10%, p = 0.008), a potent inotropic
      stimulation independent of the integrity of adrenergic cardiac receptors. A
      defective inotropic recruitment, despite the presence of a normal LV contractile
      reserve, plays an important role in deexercise LV dysfunction in diabetic
      patients with autonomic neuropathy.

PMID- 7628137
TI  - Albrecht von Haller.

PMID- 7628136
TI  - Torsade de pointes caused by high-dose intravenous haloperidol in cardiac
      patients.
AB  - Intravenous haloperidol is the agent of choice for controlling severe agitated
      delirium in seriously ill cardiac patients in many institutions. Prior reports
      have proposed that high-dose intravenous haloperidol may be without untoward
      effects in these patients. Recently, however, a few reports of significant QTc
      prolongation and torsade de pointes as complications of high-dose intravenous
      haloperidol therapy have appeared. The present report describes three patients
      with definite haloperidol-induced QTc prolongation and torsade. In each case, QTc
      prolongation preceded the arrhythmia and disappeared following the
      discontinuation of haloperidol. Neither electrolyte imbalance, therapy with other
      cardiac drugs, bradycardia, ischemia, left ventricular dysfunction, nor other
      known cause of torsade was present in these patients. It is hypothesized that QTc
      prolongation and torsade likely are idiosyncratic, unpredictable reactions to
      high-dose haloperidol in select patients. Careful serial electrocardiographic
      monitoring and prompt discontinuation of the drug should suffice to prevent this
      relatively uncommon, life-threatening complication of high-dose intravenous
      haloperidol.

PMID- 7628138
TI  - Hemobilia presenting as intermittent gastrointestinal hemorrhage with sincalide
      confirmation. A case report.
AB  - An 82-year-old man had his third episode of melanotic stool. Two previous workups
      had failed to localize the source of bleeding. A Tc-99m labeled RBC scan
      visualized the gallbladder early in the study. Administration of sincalide
      visually decreased the activity, confirming gallbladder activity. Three months
      later, at his second surgery, hepatic metastases were finally identified as the
      source of bleeding. In retrospect, the hepatic activity is inhomogeneous with at
      least two cold defects that could have represented hepatic metastases.

PMID- 7628139
TI  - Tc-99m leukocyte scintigraphy in infective endocarditis.
AB  - A 56-year-old man with Staphylococcal aureus septicemia and clinically suspected
      infective endocarditis was imaged using Tc-99m HMPAO leukocytes. Although
      abnormal uptake was seen at 3 hours after injection, 24-hour images demonstrated
      marked concentration of radiolabeled leukocytes in a myocardial abscess and large
      posterior parietal infarct. In addition, multiple splenic infarcts were shown.
      The Tc-99m labeled leukocyte scan proved to be an excellent whole body screening
      procedure for diagnosing sites of infection and infarction in this patient.

PMID- 7628140
TI  - A new thrombus imaging agent. Human recombinant fibrin binding domain labeled
      with In-111.
AB  - The amino-terminal domain of fibronectin has a fibrin binding site and a site for
      covalent cross-linking to fibrin. This fibrin binding domain was isolated from
      human recombinant fibronectin and labeled with In-111; the final molecular weight
      was 12 kD. It was applied to a pilot study of 62 patients; 30 who were thought to
      have deep vein thrombosis and 32 controls. All 30 patients had either impedance
      plethysmography, duplex ultrasound, contrast venography, or various combinations
      of the three. Eight disagreements in the 30 patients suspected of having deep
      vein thrombosis were registered between fibrin binding domain imaging and the
      other examinations. Three of the patients with negative scan results had clots
      that were 1 week old or older, and this may be a limitation of the technique. In
      three other patients who had negative scan results, but positive alternative
      studies, there was a history of previous episodes of deep vein thrombosis and
      this could be a cause of false-positive results in the other modalities. There
      was one documented false-negative scan in a fresh clot. Normal scans were
      obtained in the lower extremities of the control patients, except in two who
      demonstrated uptake at the sites of insulin injections. The initial results of
      this feasibility study are encouraging and warrant further investigation.

PMID- 7628141
TI  - Is cardiac migraine a clinical entity?
AB  - Chest pain because of a disorder of the coronary circulation is assumed to be
      ischemic in nature. Irrespective of the underlying pathophysiological mechanism,
      it is accepted that all routes lead to myocardial ischemia in the pathway to
      anginal pain. The authors describe a patient with a history of vasoactive
      disorders including migraine, asthma, documented variant angina with prolonged
      episodes of chest pain, and scintigraphic evidence of inferior and posterior wall
      ischemia during exercise and ergonovine testing in the absence of significant
      underlying stenoses. Remarkably, severe retrosternal chest pain, ST segment
      depression in multiple leads, and relative increased uptake in the inferior and
      posterior walls on Tc-99m sestamibi tomographic images developed during
      pharmacologic coronary vasodilatation with dipyridamole, leading the authors to
      speculate as to the possible existence of a nonischemic chest pain syndrome
      caused by coronary vasodilatation either in association with variant angina or as
      a separate entity.

PMID- 7628143
TI  - Hyperthyroidism after radiographic contrast in a patient with separate cervical
      and intrathoracic multinodular goiters.
AB  - The authors report a case of multinodular goiter in both cervical thyroid and
      aberrant intrathoracic thyroid tissue which was associated with thyrotoxicosis
      after the use of radiographic contrast material. The role of correlative imaging
      in assessment of cervical and anterior mediastinal masses and the phenomenon of
      iodine-induced thyrotoxicosis are also discussed.

PMID- 7628142
TI  - Tc-99m DMSA SPECT imaging in patients with acute symptoms or history of UTI.
      Comparison with ultrasonography.
AB  - Although planar cortical scintigraphy has been demonstrated to be a sensitive
      test for the detection of renal infection and scarring, one criticism has been
      radiation dose to the renal cortex. Recent studies of cortical SPECT suggest a
      sensitivity for detection of lesions equal to, or greater than, that of planar
      scans. The authors prospectively performed SPECT scans on 36 patients referred
      for recurrent urinary tract infection (UTI) (11 of 36), or recent onset of
      symptoms of UTI (25/36) after 30-40% of the standard 130 MBq (3.5 mCi) adult dose
      of Tc-99m DMSA was administered. Comparison was made with ultrasonography (US)
      performed at, or near, the same time. Of 67 kidneys evaluated, 34 (51%)
      demonstrated focal cortical loss on Tc-99m DMSA scintigraphy, 1 kidney was small
      in size, and 32 kidneys were normal. Abnormalities were noticed in only 13 (19%)
      of kidneys on US. Previously, US has been the primary imaging modality in the
      evaluation of the young patient with UTI. Triple-headed Tc-99m DMSA SPECT
      scintigraphy is a more sensitive, low-dose (12 mGy, 1.2 r) method of detecting
      renal cortical abnormalities. As such, it is a more appropriate test for
      identifying sites of cortical infection and scarring and for following patients
      on prophylactic therapy for evidence of asymptomatic break-through infections.

PMID- 7628144
TI  - Graves' disease and concurrent thyroid carcinoma. The importance of thyroid
      scintigraphy in Graves' disease.
AB  - A woman with Graves' disease and unsuspected coexisting thyroid cancer is
      presented. Although rare, this association has to be considered. It has been
      noticed that thyroid cancer is more common in hyperthyroid than euthyroid
      persons. Thus, thyroid scintigraphy is very important in the initial workup of
      Graves' disease. It helps determine whether medical or surgical therapy is more
      appropriate in a particular patient.

PMID- 7628145
TI  - Krukenberg tumor and lung metastases from colon carcinoma diagnosed with F-18 FDG
      PET.
AB  - The authors report a case of a patient with postsurgical colorectal carcinoma and
      metastatic disease to the ovaries (Krukenberg tumor), the lung, and the liver
      first revealed by F-18 FDG PET imaging. The value of PET in a patient with an
      unexplained rising CEA is cited.

PMID- 7628146
TI  - I-123 iodoamphetamine lung scanning in patients with ventilation-perfusion
      mismatching.
AB  - I-123 IMP is a nonparticulate agent and becomes trapped by endothelial membranes
      in the pulmonary capillaries. Using I-123 IMP, the authors studied six patients
      with ventilation-perfusion mismatch. Three of six patients had pulmonary
      thromboembolism, and three had pulmonary hypertension. In comparison with
      conventional perfusion lung scanning using Tc-99m MAA, defect sizes visualized by
      I-123 IMP were smaller in all patients. I-123 iodoamphetamine is a useful agent
      for assessing the perfusion of pulmonary arterial microvasculature which Tc-99m
      MAA fails to penetrate.

PMID- 7628147
TI  - A comparative study between planar Ga-67, Tl-201 images, chest x-ray, and x-ray
      CT in inoperable non-small cell carcinoma of the lung.
AB  - Seventy patients with newly diagnosed, pathologically proven inoperable non-small
      cell lung cancer (NSCLC) had planar Ga-67, Tl-201, chest x-ray, and chest CT
      imaging performed. Tumor/Normal tissue background (T/B) ratio was calculated for
      62 Ga-67 and 55 Tl-201 scintigraphy studies and comparisons were made between Ga
      67 and Tl-201 imaging results regarding T/B ratios, site of lesion, and
      histologic type. The impact of the images on the initial knowledge of the extent
      of the tumor and on the radiotherapy (RT) planning was evaluated for each
      patient. For primary lesions, Ga-67 imaging results were positive in 94% (66 of
      70 patients) versus 71% (50 of 70 patients) for Tl-201 scans (P < 0.005) and the
      T/B ratio was > 1.5 in 74% (46 of 62 patients) for Ga-67 versus 36% (20 of 55
      patients) for Tl-201 (P < 0.0001). For centrally located lesions, sensitivity for
      Ga-67 was 100% (53 of 53 patients) versus 74% (39 of 53 patients) for Tl-201 (P <
      0.0005) and the T/B ratio > 1.5 in 84% (38 of 45 patients) for Ga-67 versus 38%
      (15 of 40 patients) for Tl-201 (P > 0.001). For peripheral lesions, sensitivity
      of Ga-67 was 76% (13 of 17 patients) versus 64% (11 of 17) for Tl-201 (P > 0.05)
      and the T/B ratio was > 1.5 in 47% (8 of 17 patients) for Ga-67 versus 33% (5 of
      15 patients) for Tl-201 (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7628148
TI  - Diffusely increased colonic F-18 FDG uptake in acute enterocolitis.
AB  - A 60-year-old woman with a remote history of colon carcinoma was studied with F
      18 FDG PET imaging 5 days after admission for acute toxigenic enterocolitis.
      Marked and diffusely increased uptake was noticed throughout the ascending and
      transverse colon, which was noticed to be edematous and thickened on contrast CT
      examination. The study emphasizes the need to consider nonneoplastic entities,
      such as enterocolitis in the differential diagnosis of intensely hypermetabolic
      colonic lesions on F-18 FDG PET examinations.

PMID- 7628150
TI  - Use of Tc-99m sestamibi infusion for detection of hibernating myocardium. A
      preliminary report.
AB  - To evaluate whether a prolonged infusion of Tc-99m sestamibi allows for
      visualization of viable myocardium in areas of hypoperfused myocardium, 25
      patients were prospectively studied. Each patient was imaged four times in two
      consecutive days in the following manner: day 1:1) immediately after injection of
      Tl-201 at rest, 2) 1 hour after a bolus injection of Tc-99m sestamibi at rest;
      and day 2: 1) imaging in the Tl-201 window for 24 hour redistribution, 2) imaging
      after a 1-hour infusion of Tc-99m sestamibi. The two Tc-99m sestamibi and two Tl
      201 studies were evaluated for presence of redistribution. This was present both
      on the Tl-201 and Tc-99m sestamibi studies (concordant) in 13 cases, and absent
      on both the Tl-201 and Tc-99m sestamibi studies (concordant) in 9 cases. In two
      cases redistribution was seen on the Tl-201 images only, and in one case it was
      seen on the Tc-99m sestamibi images only (discordant). Tc-99m sestamibi infusion
      may provide information about the presence of viable myocardium which is similar
      to that provided by Tl-201 24-hour imaging.

PMID- 7628149
TI  - Inferior vena cava occlusion with pulmonary embolism because of complications due
      to ruptured abdominal aneurysm demonstrated by radionuclide venography.
AB  - A 66-year-old man with an abdominal aortic aneurysm confirmed by CT had bilateral
      swelling of the lower extremities with pain radiating to the back. Radionuclide
      venography and pulmonary scintigraphy demonstrated occlusion of the inferior vena
      cava and multiple pulmonary emboli, with a hot spot in the liver. Surgery
      revealed a ruptured abdominal aortic aneurysm that occluded the inferior vena
      cava, fistula formation, and extensive thrombosis of the inferior vena cava
      proximal to the occlusion site. Radionuclide venography was useful in detecting
      venous obstruction and the collateral formation represented by the hot spot in
      the liver as complications of the ruptured abdominal aortic aneurysm, and in
      assessing the improvement of pulmonary embolism by medical therapy.

PMID- 7628151
TI  - Better visualization of retinoblastoma metastases with Tc-99m sestamibi versus Tl
      201.
AB  - Tc-99m sestamibi has been shown to accumulate in several primary malignant
      tumors, but data regarding its use in the detection of distant metastases are
      limited. Despite its physical limitations, Tl-201 now has a definite place in the
      routine evaluation of certain primary and metastatic tumors. This report
      describes the value of Tc-99m sestamibi and its superiority to Tl-201 in the
      visualization of distant metastases in a 2-year-old girl with bilateral
      retinoblastoma. Three sites of soft tissue and bone metastasis were demonstrated
      by Tc-99m sestamibi imaging. Of these metastases, the one in the parieto
      occipital region showed evident Tl-201 uptake, while the other two in the right
      arm and chest wall showed only slightly increased uptake, which could hardly be
      spotted without the confirmation of a later Tc-99m sestamibi scan. The
      scintigraphic findings were confirmed with histopathologic examination. Tc-99m
      sestamibi scan is effective and superior to Tl-201 in the detection of distant
      soft tissue and bone metastases from retinoblastoma.

PMID- 7628152
TI  - Evaluation of tissue perfusion by the Xe-133 washout method in lower limbs of
      patients with noninsulin-dependent diabetes mellitus.
AB  - Ischemia is thought to be a major component in the pathogenesis of foot problems.
      The authors use the Xe-133 washout method to evaluate the blood perfusion of
      muscle tissue in the lower legs of patients with noninsulin-dependent diabetes
      mellitus (NIDDM). Eighty-five male patients with NIDDM ranging in age from 51
      years to 79 years (mean, 66.5 years) and 47 nondiabetic control males with a
      matched age ranging from 52 years to 82 years (mean, 64.5 years) were included in
      this study. None of the diabetics had a history or presentation of peripheral
      vascular disease in the lower limbs. The patients were separated into groups
      according to the duration of the disease and condition of blood sugar control.
      The Xe-133 washout method was performed in the anterior tibial muscle of all the
      subjects. According to a Student's t-test, the tissue perfusion were of
      significant difference between 1) NIDDM and normal controls (1.98 +/- 1.39 ml/100
      g/minute versus 2.85 +/- 1.35 ml/100 g/minute), 2) good and poor blood sugar
      control (2.36 +/- 1.58 versus 1.51 +/- 0.94), and 3) long and short disease
      durations (1.50 +/- 0.78 versus 2.35 +/- 1.63). It is concluded that the tissue
      perfusion in the lower legs of patients with NIDDM is significantly decreased and
      related to the duration of the disease and condition of blood sugar control. This
      may contribute to the high incidence of foot gangrene and limb loss in patients
      with NIDDM.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7628153
TI  - Cholescintigraphic images in a patient with hepatocellular carcinoma and Oriental
      cholangitis.

PMID- 7628154
TI  - Renal scintigraphy of an infarction in an en bloc transplantation of a horseshoe
      kidney.

PMID- 7628155
TI  - Pericardial effusion in primary hypothyroidism. Tc-99m sestamibi imaging.

PMID- 7628156
TI  - Incidental demonstration of hepatic amebic abscess by triple-phase bone
      scintigraphy.

PMID- 7628157
TI  - Focal defect in liver colloid scan due to intrahepatic gallbladder.

PMID- 7628158
TI  - Aspergilloma of the thoracic wall. Another cold spot lesion on bone scanning.

PMID- 7628159
TI  - Reversible perfusion disorder on brain SPECT after treatment with prednisone in
      temporal arteritis.

PMID- 7628160
TI  - Endobronchial lesion from metastatic ovarian carcinoma resulting in partial right
      mainstem obstruction demonstrated by lung scintigraphy.

PMID- 7628161
TI  - Imaging of an undifferentiated epidermoid carcinoma with Tc-99m MIBI.

PMID- 7628162
TI  - Thallium and gallium scintigraphy in pulmonary Kaposi's sarcoma in an HIV
      positive patient.

PMID- 7628163
TI  - Current readings in nuclear medicine.

PMID- 7628164
TI  - Bone mineral content in nephrotic children on long-term, alternate-day prednisone
      therapy.
AB  - Bone mineral content (BMC) was measured by single-photon absorptiometry in 24
      children with steroid-dependent, minimal-lesion nephrotic syndrome after 1 to 6.3
      years of alternate-day prednisone therapy and in a sex- and age-matched control
      group. Bone mineral content was -0.002 +/- 1.2 standard deviation scores in
      patients and 0.3 +/- 1.4 in controls (t = 1.17; P = 0.25). No significant
      relation was found between BMC in patients and the amount of prednisone taken or
      the duration of therapy. Alternate-day prednisone therapy at doses usually needed
      to keep children with steroid-dependent nephrotic syndrome under control does not
      significantly affect BMC.

PMID- 7628165
TI  - Clinical use of bone densitometry in children: are we ready yet?

PMID- 7628166
TI  - Neonatal-onset chronic intestinal pseudo-obstruction syndrome.
AB  - Between January 1985 and January 1990, six cases of neonatal-onset chronic
      intestinal pseudo-obstruction syndrome (CIPS) were identified. Failure to gain
      weight in six cases, abdominal distention in five, and vomiting in five were the
      most common presenting symptoms. The contrast studies of the gastrointestinal
      tract demonstrated delayed transit time in 6/6, jejunal or ileal dilatation in
      1/6, megaduodenum in 1/6, dilatation of the colon with barium retention in 4/6,
      and microcolon in 1/6. Urinary tract involvement was noted in three patients.
      Laparotomy, performed in three patients, revealed no mechanical obstruction.
      Except for hypoganglionosis in Patient 4, no recognizable neuropathy or myopathy
      was noted histopathologically. Four patients expired within 2 months after
      discharge. We conclude that CIPS with neonatal onset should be suspected when
      infants have urinary retention and abdominal distention or constipation beginning
      at birth or soon after. The prognosis of CIPS presenting in the newborn period
      appears worse than that presenting in childhood or adulthood.

PMID- 7628167
TI  - The Ohio Bicycle Injury Study.
AB  - To understand bicycle injuries and determine how to prevent them, we designed
      prospectively a descriptive study of bicycle-crash-related admissions in July
      1993 to 10 major Ohio hospitals that admit child trauma patients. All patients
      studied were under the age of 16. In the 52 cases (38 male, 73%), impact with
      another vehicle accounted for 23 (44%) crashes. Of these crashes, only three
      (13%) were caused by definite motor vehicle operator error, and all 20 (87%) of
      the remaining motor vehicle-bicycle collisions were caused by bicyclist error,
      including 10 (43%) caused by bicyclists failing to yield properly at an
      intersection. Head injuries were the primary cause of morbidity in 29 (56%)
      cases. No child was wearing a bicycle helmet at the time of the crash. Efforts to
      reduce childhood morbidity from bicycle-related crashes should focus on helmet
      education and safe riding skills.

PMID- 7628168
TI  - Current recommendations for children with urinary tract infections.

PMID- 7628169
TI  - Milk intolerance presenting solely as periorbital edema.

PMID- 7628170
TI  - Treatment of childhood chronic idiopathic thrombocytopenic purpura with
      ascorbate.

PMID- 7628171
TI  - Testotoxicosis. An unusual presentation and novel gene mutation.

PMID- 7628172
TI  - Respiratory failure caused by Lemierre's syndrome.

PMID- 7628174
TI  - Retinal hemorrhages associated with spinal cord arteriovenous malformation.

PMID- 7628173
TI  - Hearing hazard of toy cellular telephones and walkie-talkies.

PMID- 7628175
TI  - Human tails and associated spinal anomalies.
AB  - Human tails have been described intermittently in the literature, typically as
      isolated cases with varying forms of malformation. Attempts have been made to
      differentiate "true" tails from "tail-like" appearances. Unless identified,
      underlying occult spinal disorders, mass effect, and/or tethering of the spinal
      cord may lead to progressive neurologic damage. We report three patients with
      "tails" and the associated spinal anomalies.

PMID- 7628176
TI  - Success rates for new drugs entering clinical testing in the United States.

PMID- 7628177
TI  - Drug safety discontinuations in the United Kingdom, the United States, and Spain
      from 1974 through 1993: a regulatory perspective.
AB  - The objective of the present study was to compare the number of new chemical
      entities (NCEs) and new biologicals entities (NBEs) approved for marketing during
      the period 1974 through 1993 in the United Kingdom, the United States, and Spain
      that were subsequently discontinued (removed from the market, withdrawn, or whose
      license was allowed to lapse) while a question of safety existed. Of the products
      approved during the two decades of the study period, a total of 29 drugs were
      subsequently discontinued for safety reasons in at least one of the three
      countries (United Kingdom: 20 safety discontinuations; United States: 10; and
      Spain: 16). These represent 3% to 4% of all drugs introduced in these countries,
      an increase compared to the period from 1964 through 1983, when approximately 2%
      of all NCEs were discontinued for safety reasons. The therapeutic classes most
      commonly associated with safety discontinuations were the nonsteroidal anti
      inflammatory drugs (nine drugs), vasodilators (four drugs), and antidepressants
      (three drugs). U.S. companies or their foreign subsidiaries were involved as
      originators (patent-holders and/or developers) of approximately 40% of the drugs
      discontinued for safety reasons.

PMID- 7628178
TI  - The effects of ketoconazole on the intestinal metabolism and bioavailability of
      cyclosporine.
AB  - The pharmacokinetics of cyclosporine were studied in the blood of five normal
      healthy volunteers (two men and three women) after each received oral and
      intravenous cyclosporine alone and with concomitant oral ketoconazole.
      Administration of ketoconazole caused a significant decrease in intravenous
      cyclosporine clearance (0.18 +/- 0.05 L/kg/hr versus 0.32 +/- 0.09 L/hr/kg) and a
      significant increase in cyclosporine oral bioavailability (56.4% +/- 11.7% versus
      22.4% +/- 4.8%) compared with values before ketoconazole administration. Steady
      state volume of distribution for intravenously administered cyclosporine was
      unchanged (1.26 +/- 0.44 L/kg versus 1.10 +/- 0.27 L/kg). Hepatic bioavailability
      (1 - hepatic extraction ratio) calculated for intravenous cyclosporine increased
      by 11% in the presence of ketoconazole (86.3% +/- 3.7% versus 75.2% +/- 6.6%
      without ketoconazole), which accounts for only one third of the observed increase
      in cyclosporine oral bioavailability. Because it is unlikely that ketoconazole
      had a significant effect on either cyclosporine absorption or hepatic blood flow,
      the increase in cyclosporine bioavailability observed in this study is most
      likely explained by inhibition of gastrointestinal cytochrome P450 enzymes.

PMID- 7628179
TI  - Interaction between grapefruit juice and midazolam in humans.
AB  - OBJECTIVE: To investigate the effects of grapefruit juice on the pharmacokinetics
      and dynamics of midazolam. METHODS: Eight healthy male subjects participated in
      this open crossover study. Intravenous (5 mg) or oral (15 mg) midazolam was
      administered after pretreatment with water or grapefruit juice. We measured the
      pharmacokinetics and pharmacodynamics (reaction time, Digit Symbol Substitution
      Test [DSST], general impression judged by the investigators, and drug effect
      judged by the subjects) of midazolam and the pharmacokinetics of alpha
      hydroxymidazolam. RESULTS: In comparison to water, pretreatment with grapefruit
      juice did not change the pharmacokinetics or pharmacodynamics of intravenous
      midazolam. After oral administration, pretreatment with grapefruit juice led to a
      56% increase in peak plasma concentration (Cmax), a 79% increase in time to reach
      Cmax (tmax), and a 52% increase in the area under the plasma concentration-time
      curve (AUC) of midazolam, which was associated with an increase in the
      bioavailability from 24% +/- 3% (water) to 35% +/- 3% (Grapefruit juice; mean +/-
      SEM, p < 0.01) After oral administration of midazolam, pretreatment with
      grapefruit juice was associated with a 105% increase in tmax and with a 30%
      increase in the AUC of alpha-hydroxymidazolam. For oral midazolam, pretreatment
      with grapefruit juice led to significant increases in tmax for all dynamic
      parameters and in the AUC values for the reaction time and DSST, whereas the
      maximal dynamic effects remained unchanged. CONCLUSIONS: Pretreatment with
      grapefruit juice is associated with increased bioavailability and changes in the
      pharmacodynamics of midazolam that may be clinically important, particularly in
      patients with other causes for increased midazolam bioavailability such as
      advanced age, cirrhosis of the liver, and administration of other inhibitors of
      cytochrome P450.

PMID- 7628180
TI  - Comparison of the prevalence of the poor metabolizer phenotype for CYP2D6 between
      203 Hmong subjects and 280 white subjects residing in Minnesota.
AB  - Genetic polymorphism of the P450IID6 (CYP2D6) enzyme system can be an important
      component of the variability in response to drug therapy. Interpopulation
      differences in the prevalence of deficiencies of drug-metabolizing enzymes may be
      clinically important in the selection and dosage of drug therapies for patients.
      Since 1980, the State of Minnesota has had more than a 1000% increase in
      population of Hmong refugees from Laos. The Hmong are frequently treated in our
      institution's international clinic with virtually no systematically acquired
      knowledge about the ability of this relatively ethnically pure population to
      metabolize commonly used Western medications. To further our knowledge of drug
      metabolism in this population, we identified the prevalence of the poor
      metabolizer phenotype for CYP2D6 in a sample population of Hmong subjects and
      compared this prevalence to that in a sample population of white subjects. Urine
      collected after ingestion of dextromethorphan in 237 healthy Hmong and 280
      healthy white volunteers was analyzed by HPLC. Based on probit plots of the
      metabolic ratios (dextro-methorphan/dextrorphan), 8.9% of Hmong subjects and 6.1%
      of white subjects were assigned the poor metabolizer phenotype (difference not
      significant). Weak associations were found between body surface area and
      metabolic ratio for both Hmong and white men and between smoking status and
      metabolic ratio for white subjects only. We conclude that the prevalence of poor
      metabolizers for the CYP2D6 enzyme system is similar between Hmong subjects and
      white subjects residing in Minnesota and that an antimode of 0.3 for metabolic
      ratio appears to be reasonable for the populations studied.

PMID- 7628181
TI  - Simultaneous modeling of the pharmacokinetics and pharmacodynamics of midazolam
      and diazepam.
AB  - The pharmacokinetics and pharmacodynamics of midazolam and diazepam were compared
      after intravenous infusions of 0.03 and 0.07 mg/kg midazolam and 0.1 and 0.2
      mg/kg diazepam on four separate occasions in 12 healthy male subjects in a
      randomized four-way crossover design. The Digit Symbol Substitution Test (DSST)
      was used as a measure of drug effect. Subjects performed three practice tests
      before dosing to account for any effects caused by familiarization ("learning
      curve") with the testing procedure. Pharmacokinetic and pharmacodynamic data were
      simultaneously fitted to a semiparametric model. In this model, a pharmacokinetic
      model related dose to plasma concentrations, a link model related plasma
      concentrations to the concentration at the effect site, and a pharmacodynamic
      model related the effect site concentration to the observed effect. The plasma
      effect site equilibrium half-life was approximately 2 1/2 times longer for
      midazolam than for diazepam, which is in good agreement with previously published
      data. Based on the estimated effect site concentration at which half of the
      maximal effect was reached, midazolam had approximately a sixfold greater
      intrinsic potency than diazepam. This difference in potency was also observed in
      a previous study that used transformed electroencephalographic (EEG) data to
      assess pharmacodynamic activity. The findings reported here with a clinically
      relevant pharmacodynamic marker (DSST) confirm the utility of surrogate drug
      effect measures such as EEG. This work also shows the feasibility of conducting
      pharmacokinetic pharmacodynamic analysis during the drug development process.

PMID- 7628182
TI  - Pharmacokinetics of an anti-human immunodeficiency virus antisense
      oligodeoxynucleotide phosphorothioate (GEM 91) in HIV-infected subjects.
AB  - Human pharmacokinetics of an antisense oligodeoxynucleotide phosphorothioate (GEM
      91) developed as an anti-human immunodeficiency virus (HIV) agent was carried out
      in this study. 35S-Labeled GEM 91 was administered to six HIV-infected
      individuals by means of 2-hour intravenous infusions at a dose of 0.1 mg/kg.
      Plasma disappearance curves for GEM 91-derived radioactivity could be described
      by the sum of two exponentials, with half-life values of 0.18 +/- 0.04 and 26.71
      +/- 1.67 hours. The radioactivity in plasma was further evaluated by
      polyacrylamide gel electrophoresis, showing the presence of both intact GEM 91
      and lower molecular weight metabolites. Urinary excretion represented the major
      pathway of elimination, with 49.15% +/- 6.80% of the administered dose excreted
      within 24 hours and 70.37% +/- 6.72% over 96 hours after dosing. The
      radioactivity in urine was associated with lower molecular weight metabolites. No
      drug-related toxicity was observed.

PMID- 7628183
TI  - Acetylcholinesterase inhibition by zifrosilone: pharmacokinetics and
      pharmacodynamics.
AB  - OBJECTIVE: To determine the pharmacokinetics, pharmacodynamics and safety of the
      acetylcholinesterase inhibitor zifrosilone in healthy male volunteers. METHODS:
      Pharmacokinetics, pharmacodynamics, and tolerance of zifrosilone were studied in
      a double-blind, sequential, single-escalating-dose, randomized panel design. Each
      panel consisted of six subjects, with four subjects receiving zifrosilone (10,
      30, 60, 90, 120, 150, 200, 250, and 300 mg orally) and two subjects receiving
      matching placebo. Serial blood samples were obtained for zifrosilone plasma
      concentrations and red blood cell acetylcholinesterase and butyrylcholinesterase
      activities. Participating subjects (n = 54) were men between the ages of 18 and
      45 years. Each subject had a normal physical examination, electrocardiogram,
      serum chemistries, hematology, urinalysis, and test for human immunodeficiency
      virus at screening. RESULTS: A greater than proportionate increase in mean plasma
      concentration values for area under the curve from time zero to infinity was
      observed over the 200 to 300 mg dose range groups. Red blood cell
      acetylcholinesterase showed a dose-inhibition relationship, with a mean maximum
      inhibition of 20.9% at 10 mg that increased to 62.1% at 300 mg.
      Butyrylcholinesterase activity was relatively unaffected by zifrosilone (< 20%
      inhibition at 300 mg). For doses > or = 200 mg, an Emax pharmacodynamic model was
      used to describe the relationship between zifrosilone plasma concentration and
      red blood cell acetylcholinesterase inhibition (Emax = 83.8%; EC50 = 0.65 ng/ml).
      CONCLUSIONS: Zifrosilone showed dose-dependent pharmacokinetics after oral
      administration and was effective in causing selective inhibition of red blood
      cell acetylcholinesterase.

PMID- 7628184
TI  - Interethnic difference in omeprazole's inhibition of diazepam metabolism.
AB  - OBJECTIVES: To compare the effect of omeprazole, a substrate and inhibitor of
      CYP2C19, on diazepam metabolism in white and Chinese subjects. SUBJECTS AND
      METHODS: The study, which took place at a clinical research center in a
      University Hospital, was designed as a double blind, crossover, two-stage study;
      each stage lasted 21 days and was separated by 4 weeks. Subjects were eight white
      and seven Chinese men who were extensive metabolizers of debrisoquin and
      mephenytoin. The subjects received, in a randomized order, omeprazole, 40 mg/day,
      and placebo for 21 days, followed by a 10 mg oral dose of diazepam. Diazepam and
      desmethyldiazepam plasma concentrations were determined by HPLC during a 26-day
      period after diazepam administration. RESULTS: In white subjects omeprazole
      treatment decreased diazepam clearance by 38% +/- 4.4% and increased
      desmethyldiazepam area under the plasma concentration-time curve (AUC) by 42.4%
      +/- 7.0%. In contrast, diazepam oral clearance decreased by only 20.7% +/- 7.3%
      and desmethyldiazepam AUC decreased by 25.4% +/- 4.6% in the Chinese group. The
      decrease in diazepam clearance and the prolongation in diazepam and
      desmethyldiazepam elimination half-lives after administration of omeprazole were
      significantly greater in the white group than in the Chinese group (p < 0.03, p <
      0.001, and p < 0.004, respectively). In the absence of omeprazole, diazepam oral
      clearance was marginally greater (mean +/- SEM) (34.4 +/- 2.8 ml/min versus 25.2
      +/- 3.5 ml/min, p = 0.057, respectively) and the AUC of desmethyldiazepam was
      significantly lower (8794 +/- 538 micrograms/L.hr versus 16,358 +/- 2985 mg/L.hr,
      p = 0.04, respectively) in the white subjects compared with the Chinese subjects.
      CONCLUSION: The extent of the inhibitory effect of omeprazole on diazepam
      metabolism is dependent on ethnicity. Further studies are needed to determine the
      mechanism responsible for this phenomenon.

PMID- 7628185
TI  - H1- and H2-histamine receptor-mediated vasodilation varies with aging in humans.
AB  - INTRODUCTION: Aging is associated with alterations in the responses to several
      important vasoactive drugs. We have investigated histamine-mediated venodilation
      across the adult age range using the human hand vein compliance technique.
      Histamine produces dilation in human veins by activating both H1- and H2
      receptors. METHODS: Full dose-response curves to histamine were constructed in 16
      healthy volunteers (mean age, 47 +/- 20 years; age range, 21 to 80 years) by
      infusing histamine (2 to 136 ng/min) into dorsal hand veins preconstricted with
      the alpha-adrenergic selective agonist phenylephrine. RESULTS: Histamine was an
      efficacious venodilator across the age range; the average maximal response (Emax)
      was 122 +/- 45% and the geometric mean ED50 (the dose producing half-maximal
      response) was 16.6 ng/min for all subjects. Dose-response curves to histamine
      were repeated after infusion of the H2-selective antagonist cimetidine at a dose
      sufficient to completely block the H2-mediated response (49 micrograms/min).
      Cimetidine did not inhibit the Emax in the elderly as much as it did in the young
      subjects. The Emax to histamine in the presence of cimetidine plotted against age
      showed a significant relationship (r = 0.62, p = 0.02). CONCLUSIONS: These
      results suggest that, although the overall histamine-induced venodilation is
      conserved in aging, there is a loss of the signal transduction pathway activated
      by way of H2-receptors but no loss in function of H1-receptors. Consequently,
      these results suggest differential changes in function of H1- versus H2-histamine
      receptors with aging. Because H1-receptors are coupled to endothelial-derived
      relaxing factor release and because H2-receptors activate cyclic adenosine
      monophosphate in smooth muscle, the results are compatible with hypothesis that
      there are specific changes in these signal transduction pathways with aging.

PMID- 7628186
TI  - Glucocorticoid-induced sympathoinhibition in humans.
AB  - OBJECTIVE: To test whether glucocorticoids inhibit sympathetic nerve activity or
      norepinephrine release in humans, as has been suggested by results in laboratory
      animals. METHODS: This was a double-blind, placebo-controlled, randomized
      crossover study performed at the Clinical Center of the National Institutes of
      Health. Thirteen normal volunteers received 20 mg prednisone or placebo orally
      each morning for 1 week, followed by a washout period of 1 week and then by
      treatment with the other drug for 1 week. On the last day of each treatment week,
      blood samples were drawn for measurements of plasma levels of catecholamines and
      their metabolites, of cortisol, and of corticotropin at baseline and during
      reflexive sympathetic stimulation elicited by lower body negative pressure (-15
      mm Hg). A 24-hour urine collection was obtained at the end of each week of
      treatment for measurement of urinary excretion of catechols. In eight subjects,
      directly recorded peroneal skeletal muscle sympathetic nerve activity was also
      measured after both treatments. RESULTS: Prednisone significantly decreased
      sympathetic nerve activity by 23% +/- 6%, plasma norepinephrine levels by 27% +/-
      6%, and plasma corticotropin levels by 77%. Blood pressure, heart rate, body
      weight, and urinary excretion of catechols and electrolytes were unaffected.
      Prednisone did not alter proportionate increments in sympathetic nerve activity
      or plasma norepinephrine levels during lower body negative pressure.
      Relationships between sympathetic nerve activity and plasma norepinephrine levels
      were unchanged. CONCLUSIONS: Glucocorticoids decrease sympathoneural outflows in
      humans without affecting acute sympathoneural responses to decreased cardiac
      filling and probably without affecting presynaptic modulation of norepinephrine
      release.

PMID- 7628187
TI  - Pharmacokinetics and pharmacodynamics of 21-day continuous oral etoposide in
      pediatric patients with solid tumors.
AB  - PURPOSE: The objectives of this study were to determine etoposide
      pharmacokinetics during continuous low-dose oral administration to children with
      solid tumors and to evaluate the relationships between parameters of etoposide
      systemic exposure and toxicity. PATIENTS AND METHODS: In this phase I study,
      children were administered oral etoposide (25 to 75 mg/m2/day) for 21 days as a
      diluted solution of the intravenous preparation, divided into three equal daily
      doses. Plasma pharmacokinetics were studied on day 1 of therapy in 18 children
      and again on day 21 in 14 of these children. Etoposide plasma concentration-time
      data were fitted to a first-order absorption, two-compartment model with use of
      bayesian estimation. Pharmacokinetic parameter estimates from day 1 were used to
      estimate steady-state etoposide systemic exposure in all children. Stepwise
      multivariate regression was used in an exploratory manner to determine patient,
      laboratory, or pharmacokinetic predictors of toxicity. RESULTS: Although there
      was substantial intrapatient variability, there was no difference in the area
      under the concentration-time curve [AUC(0-8hr)] measured at day 21 compared with
      the steady-state AUC(0-8hr) estimated from day 1 pharmacokinetic parameters (p =
      0.64). Degree of neutropenia was best predicted by the estimated duration that
      steady-state plasma etoposide concentrations were maintained above 1 microgram/ml
      (t > 1 microgram/ml) rather than peak plasma concentrations, AUC(0-8hr), dosage,
      or other patient characteristics. Assuming a bioavailability of the oral solution
      of approximately 50%, the median etoposide systemic clearance was 21.4 ml/min/m2,
      a value similar to clearance estimates after intravenous etoposide in pediatric
      populations. CONCLUSION: We conclude that a parameter reflective of etoposide
      systemic exposure (t > 1 microgram/ml) correlates more strongly with neutropenia
      than does dosage or other patient characteristics.

PMID- 7628188
TI  - Pneumonia with pleural effusion due to Legionella pneumophila serogroup Lansing
      3.
AB  - We describe a case of pneumonia with pleural effusion due to Legionella
      pneumophila serogroup Lansing 3 in a human immunodeficiency virus-infected
      person. The 55-year-old man had been treated with immunosuppressive agents for
      hypersensitivity pneumonitis.

PMID- 7628189
TI  - Antimicrobial activity of 11 newer and investigational drugs tested against
      aerobic isolates from spontaneous bacterial peritonitis.
AB  - The in vitro susceptibility of 124 aerobic bacterial pathogens isolated from
      patients with spontaneous bacterial peritonitis (SBP) were tested against 11
      antimicrobial agents, including parenteral or oral cephalosporins and
      fluoroquinolones. Most SBP isolates were Gram-negative organisms, and Escherichia
      coli and Klebsiella pneumoniae were responsible for 63% of the episodes
      evaluated. The fluoroquinolones (ciprofloxacin and ofloxacin) and the "fourth
      generation" cephalosporin cefpirome were the most active agents against the Gram
      negative bacteria. Commonly used cefotaxime and cefotaxime-desacetylcefotaxime
      (DES-CTX) combinations were also very active against Gram-negative bacteria with
      only few Enterobacter cloacae isolates being resistant (minimum inhibitory
      concentrations > 32 micrograms/ml). All streptococci were susceptible to
      cefotaxime, cefpirome, and cefdaloxime and to the cefotaxime-DES-CTX
      combinations, whereas only ofloxacin demonstrated acceptable activity against the
      enterococci. The widest spectrum of activity versus SBP isolates was found for
      ofloxacin (98% susceptibility) among the fluoroquinolones. For the beta-lactams,
      the widest spectrum of activity was demonstrated by cefpirome and the 2:1
      cefotaxime-DES-CTX combination (93% susceptibility). These results indicate that
      the role of ofloxacin and newer parenteral or orally administered cephalosporins
      in the treatment of prophylaxis of SBP should be further evaluated.

PMID- 7628191
TI  - Evaluation of the Etest for penicillin susceptibility testing of Neisseria
      meningitidis.
AB  - Susceptibility to penicillin of 30 strains (one isolate per patient) of Neisseria
      meningitidis isolated from blood (N = 19) or cerebrospinal fluid (N = 11) was
      studied by two methods. Minimum inhibitory concentrations (MICs) obtained with
      the Etest were compared to those obtained by the National Committee for Clinical
      Laboratory Standards agar dilution method. Twenty meningococci (67%) relatively
      resistant to penicillin were identified by both methods. The mean MIC from the
      reference method was 0.32 micrograms/ml (range, 0.2-1) and by the Etest method
      was 0.35 micrograms/ml (range, 0.19-1.25). All MICs obtained by the Etest method
      were within one dilution of the MICs obtained by the reference method. Because of
      the increase in penicillin MIC of meningococcal isolates in Spain, we evaluated
      the performance of the Etest as an alternative method for penicillin
      susceptibility testing of N. meningitidis. The Etest is a simple and accurate
      method for determining the susceptibility of N. meningitidis to penicillin.

PMID- 7628190
TI  - In vitro activity of beta-lactamase inhibitors against clinical isolates of
      Acinetobacter species.
AB  - Acinetobacter is an important cause of nosocomial infections, and it is often
      resistant to many antibiotics. In a search for alternative agents, three beta
      lactamase inhibitors (sulbactam, clavulanate, and tazobactam) and five beta
      lactam antibiotics (imipenem, ceftazidime, ceftriaxone, cefotaxime, and
      piperacillin) were tested against 68 unique clinical isolates of Acinetobacter
      species. Minimum inhibitory concentrations were determined by a broth
      microdilution method. Using temperature sensitivity testing, we identified 59
      strains as Acinetobacter baumannii, one as Acinetobacter haemolyticus, and eight
      as indeterminate biotype species. We demonstrated 41 of 59 (70%) strains of A.
      baumannii to be multiply resistant (susceptible only to amikacin and imipenem),
      whereas all the nonbaumannii strains were not. Imipenem was the most active agent
      among the compounds investigated. All three beta-lactamase inhibitors had strong
      intrinsic activity, with sulbactam being the most active agent among the beta
      lactamase inhibitors studied.

PMID- 7628192
TI  - Beta-lactamase tests for screening Enterococcus faecalis isolates.

PMID- 7628193
TI  - Superiority of conventional culture technique over rapid detection of group A
      Streptococcus by optical immunoassay.
AB  - An optical immunoassay (OIA) has been reported to be more sensitive than
      conventional culture for the detection of Group A Streptococcus, eliminating the
      need for culture. We attempted to confirm the sensitivity and specificity through
      a laboratory quantitation study and a clinical trial. OIA did not detect Group A
      Streptococcus below 10(5) colony forming units (CFU). Culture detected
      Streptococcus to 10(2) CFU from the inoculated swab. In the clinical study,
      throat swabs were obtained from 77 patients in an outpatient clinic. Compared
      with culture, the sensitivity of OIA was 78% and the specificity was 90%. These
      results demonstrate that OIA was less sensitive than culture in seeded
      experiments and missed 22% of positives in clinical practice. Our study, contrary
      to previous reports, suggests that OIA is not sensitive enough to be used as the
      sole assay for Group A Streptococcus pharyngitis.

PMID- 7628194
TI  - Increased recovery of group B Streptococcus by the inclusion of rectal culturing
      and enrichment.
AB  - Detection of intrapartum carriage of group B streptococcus (GBS) and subsequent
      antibiotic prophylaxis may prevent GBS infections in neonates. Because the
      gastrointestinal tract is the primary source of this organism, detection of
      carrier status requires both rectal and vaginal swabs. Vaginal swabs from 651
      obstetric outpatients were plated onto 5% sheep blood agar. A second vaginal and
      a rectal swab were collected and incubated overnight in an enrichment medium of
      Todd-Hewitt broth containing antibiotics. By at least one method, 110 (16.9%)
      patients were positive for GBS. Only 31.8% of these positive patients were
      detected by direct culture of vaginal swabs. The use of vaginal swabs directly
      plated onto blood agar identified only three carriers not detected by another
      method. Inoculation of an enrichment broth with the vaginal swab and subsequent
      subculture detected 70.9% of the total. The use of both vaginal and rectal swabs
      with enrichment detected 97.3% of total GBS carriers. A subset of enrichment
      broths inoculated with vaginal and rectal specimens from 279 patients was tested
      for GBS by direct latex agglutination (Streptex; Murex Diagnostics, Inc.,
      Norcross, GA, USA). Of the 90 broths that grew GBS on subculture, only 59 (65.6%)
      were positive by the direct agglutination method. The use of this method,
      although reducing processing time by 1 day, gave false-negative results for one
      third of the GBS-positive broths. An accurate detection of the GBS carrier state
      can only be achieved by a combination of vaginal and rectal swabs incubated in
      enrichment broth and subcultured on blood agar.

PMID- 7628195
TI  - A prolonged outbreak of exfoliative toxin A-producing Staphylococcus aureus in a
      newborn nursery.
AB  - An outbreak of erythromycin-resistant, exfoliative toxin-producing Staphylococcus
      aureus infection in a neonatal unit is described. The organism was coagulase
      positive but staphyloslide negative, and this unusual phenotype facilitated early
      recognition of the organism in the routine laboratory. In the initial outbreak
      there were 77 probable or confirmed cases, with a peak attack rate of 66%.
      Increased infection control measures were put in place and attempts were made to
      identify a staff carrier. No carriers were found and the major outbreak subsided.
      Sporadic cases occurred over the following 10 months, until May 1992, when a
      colonized staffperson was discovered. She was treated and no further cases
      occurred. The causative organism was subjected to typing by phage,
      enterobacterial repetitive intergenic consensus sequence polymerase chain
      reaction, and pulsed-field gel electrophoresis with two separate enzymes. The
      phage typing and genomic tests confirmed the presence of the same clone in the
      unit for 9 months. The organism possessed genes encoding exfoliative toxin A as
      determined by polymerase chain reaction.

PMID- 7628196
TI  - Evaluation of a commercially available ELISA assay for detection of Giardia
      lamblia in fecal specimens.
AB  - A total of 417 fecal samples preserved in 10% buffered formalin and PVA were
      submitted to a commercial microbiology laboratory only for the detection of
      Giardia lamblia. Results from fecal specimens collected from 411 patients with
      gastrointestinal symptoms were compared using the following methods: (a) standard
      Ova & Parasite (O&P) concentration; (b) Alexon's ProspecT/Giardia enzyme-linked
      immunosorbent assay (ELISA) test, and (c) Meridian's Direct Fluorescent Antibody
      (DFA) Stain. In the 29 specimens in which G. lamblia was detected, 10 were O&P,
      DFA and ELISA positive, 17 were only ELISA positive and two were only Ova &
      Parasite and Direct Fluorescent Antibody positive. Of the 29 positive specimens,
      22 were confirmed as true positives. The ELISA sensitivity was 91% and the
      specificity was 98%. The expense associated with these methods to detect the
      presence of Giardia is $11.00, $8.95, and $12.80, respectively. In symptomatic
      patients, the ProspecT/Giardia ELISA is a cost-effective, rapid, and sensitive
      method for detecting the presence of G. lamblia in fecal specimens.

PMID- 7628197
TI  - Influence of beta-lactamase inhibitors on the activity of oxacillin against
      methicillin-resistant Staphylococcus aureus.
AB  - We studied the in vitro susceptibility to oxacillin of 46 isolates of methicillin
      resistant Staphylococcus aureus (MRSA) isolates with a minimum inhibitory
      concentration (MIC) > 8 micrograms/ml of oxacillin, with and without adding
      clavulanic acid, sulbactam, or tazobactam in three different concentrations (2,
      4, and 8 micrograms/ml). All 46 strains were found by the rapid chromogenic
      cephalosporin method to be beta-lactamase producers. For those strains with low
      level resistance (MIC of 16 or 32 micrograms/ml), the MICs of oxacillin decreased
      four- to 32-fold and two- to 32-fold after adding sulbactam and tazobactam,
      respectively. For those with high-level resistance (MIC of > or = 64
      micrograms/ml), the MICs either did not change or decreased only two-fold after
      we added one of three beta-lactamase inhibitors. The results suggest that beta
      lactamase production probably plays a role in resistance to oxacillin in those
      MRSA strains of low-level oxacillin resistance.

PMID- 7628198
TI  - Emerging multiply resistant enterococci among clinical isolates. I. Prevalence
      data from 97 medical center surveillance study in the United States. Enterococcus
      Study Group.
AB  - To assess the evolving problem of therapeutic drug resistances among enterococci,
      we organized a comprehensive national (United States) surveillance trial using 99
      recruited microbiology laboratories in 48 of the 49 contiguous states or
      districts. All but two sites completed the protocol that generated information
      from nearly 2000 enterococci, usually isolated from blood cultures. All strains
      were speciated by the same method (API 20S) and were susceptibility tested by
      three methods (broth microdilution, disk diffusion, and Etest) against
      ampicillin, penicillin, vancomycin, teicoplanin, gentamicin, and streptomycin.
      Strains resistant to a glycopeptide or penicillin, or possessing high-level
      aminoglycoside resistance were referred to the monitor's laboratory for
      validation and additional susceptibility testing against other alternative
      antimicrobial agents. The most common species were Enterococcus faecalis and
      Enterococcus faecium. However, antimicrobial resistance occurred most often among
      the E. faecium isolates. Twenty-three percent of participant centers (22 sites)
      reported 87 vancomycin-resistant isolates, which accounts for 4.4% of the
      isolates evaluated. A recent audit (March 1994) of the laboratories not reporting
      vancomycin resistance during the study interval (October-December 1992) revealed
      that 61% of sites have now recognized these strains, a threefold increase in 12
      15 months. Teicoplanin remained active against 28% (Van B phenotype) of
      vancomycin-resistant enterococci (10 E. faecalis, 13 E. faecium, and one
      Enterococcus spp.). Ampicillin-resistant beta-lactamase-positive strains were
      found only at one medical center (two strains, 0.2% of referred or validated
      strains); however, ampicillin-resistant strains represented 12% of all
      enterococcal, but nearly 60% of E. faecium strains.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7628199
TI  - Emerging multiply resistant enterococci among clinical isolates. II. Validation
      of the etest to recognize glycopeptide-resistant strains.
AB  - Accurate, quantitative susceptibility testing of the enterococci for glycopeptide
      (vancomycin and teicoplanin) activity has become very important to guide
      chemotherapy as a result of emerging resistance. Reference dilution tests using
      broth and agar are generally difficult to perform, or in some commercial forms
      have demonstrated interpretive error. An alternative method, the Etest has
      promise as a system with qualitative and quantitative accuracy. Nearly 2000
      enterococci from 97 laboratories in the United States were tested using broth
      microdilution, disk diffusion, and Etest methods. The Etest quantitative accuracy
      (+/- 1 log2 dilution) compared to the broth microdilution minimum inhibitory
      concentration was 90.1% (teicoplanin) to 94.1% (vancomycin). The qualitative
      interpretive accuracy of the Etest ranged from 98.7% for vancomycin to 99.9% for
      teicoplanin (no false-susceptible errors). All three tests were in remarkable
      agreement, with < or = 0.8% maximal discord by interpretive category. The Etest
      appears to be an excellent alternative to reference and standardized methods for
      producing quantitative activity measurements of glycopeptide susceptibility or
      resistance.

PMID- 7628200
TI  - Progestin-only pill use and pill switching during breastfeeding.
AB  - The opinions of 20 international experts in reproductive endocrinology and family
      planning service delivery were solicited concerning contraceptive pill use during
      breastfeeding and, in particular, to determine whether the experts felt that
      breastfeeding women who use progestin-only pills (POPs) should be advised to
      switch to combined estrogen-progestin pills (COCs) during lactation. The experts
      agreed that POPs can be used safely and effectively throughout the period of
      lactation and there is no need to switch to another contraceptive method or
      another type of pill. If, however, a woman wishes to switch to COCs while she is
      still breastfeeding, it is acceptable for her to do so after six months
      postpartum.

PMID- 7628201
TI  - Use and misuse of oral contraceptives: risk indicators for poor pill taking and
      discontinuation.
AB  - The contraceptive efficacy of oral contraceptives (OCs) depends on their proper
      and continued use, particularly with lower estrogen preparations. However, few
      studies have examined why women miss pills or discontinue OCs, and those that do
      tend to be small and to focus on adolescents. To address the issues of poor OC
      compliance and early OC discontinuation, we analyzed OC use in a convenience
      sample of 6,676 women between the ages of 16 and 30 from Denmark, France, Italy,
      Portugal, and the United Kingdom. Logistic regression was used to examine the
      independent effect of each factor. Poor compliance was associated with a lack of
      established routine for pill-taking (relative risk [RR] = 3.3), failure to read
      and understand written materials that came with the OC package (RR = 2.2), not
      receiving adequate information or help about OCs from their health care provider
      (RR = 1.5), and occurrence of certain side effects, including hirsutism (RR =
      2.1), nausea (RR = 1.4), bleeding irregularities (RR = 1.3), and breast
      tenderness (RR = 1.2). Women who were inconsistent OC users, missing one or more
      pills per cycle, were almost three times as likely to experience an unintended
      pregnancy while using OCs than were women who took their OCs consistently.
      Factors that predicted early discontinuation (women who wished to continue
      contraceptive protection but discontinued OC use) were primarily side effects,
      including nausea (RR = 2.1), bleeding (RR = 1.9), breast tenderness (RR = 1.8),
      mood changes (RR = 1.8), and weight gain (RR = 1.4).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7628202
TI  - Effectiveness of the non-spermicidal fit-free diaphragm.
AB  - Standard instructions for diaphragm use call for an individually sized latex
      diaphragm, used in conjunction with spermicide jelly. However, some investigators
      have reported that the diaphragm can be effective without a spermicide. A non
      randomized trial designed to measure the contraceptive effectiveness of the
      diaphragm used without spermicide was conducted. A total of 110 self-selected
      women were enrolled to use a non-spermicide fit-free (60mm) diaphragm for a
      period of one year. They were advised to wear the diaphragm continuously,
      removing it once each day for washing but not within six hours after intercourse.
      Product-related problems related to insertion, retention and removal were few at
      both the 6- and 12-month follow-up visits, most commonly odor. The 12-month life
      table accidental pregnancy rate during typical use was 24.1 per 100 women (29.5
      per 100 women without female barrier experience and 17.9 per 100 women with
      barrier experience). Over 85% of the women who returned for follow-up visits
      reported using the diaphragm during every act of intercourse. Until better data
      refute the traditional recommendations, users should be advised to add spermicide
      to fitted latex diaphragms.

PMID- 7628203
TI  - The impact of oral contraception on vulvovaginal candidiasis.
AB  - To evaluate risk factors related to sociodemographic and clinical variables, oral
      contraception and sexual behavior of women with recurrent vulvovaginal
      candidiasis, we conducted a case-control study comparing 153 patients with
      recurrent vulvovaginal candidiasis with both asymptomatic women with negative
      vaginal cultures and patients with nonrecurrent symptomatic vulvovaginal
      candidiasis. In logistic regression analysis, patients with recurrent Candida
      vaginitis were more likely than negative controls to have used any contraceptive
      method in the year before evaluation, to have used antibiotics in the month
      preceding the visit, and to have a higher number of lifetime sex partners.
      Compared to patients with nonrecurrent Candida vaginitis, patients with recurrent
      infection were more likely to use oral contraception and to have a higher
      frequency of monthly intercourse. The proportion of recur rent disease
      attributable to the pill averages 11-12%. We conclude that oral contraceptives
      may influence the recurrence of symptomatic vulvovaginal candidiasis.

PMID- 7628204
TI  - Neutralizing pH of lidocaine reduces pain during Norplant system insertion
      procedure.
AB  - The acidity of lidocaine used as a local anesthetic during the insertion of
      Norplant System capsules can cause patient discomfort. Buffering lidocaine with
      sodium bicarbonate significantly reduced pain scores reported by 46 women who
      participated in this randomized, double-blind study. Derived from a pain scale of
      1 to 10, the mean difference in reported pain scores with and without buffering
      was 1.17 (P = 0.0098) with women using themselves as controls, for an average
      reduction in pain of 29%. Because this added step minimized patient discomfort,
      it might make the Norplant System a more attractive option for women apprehensive
      about insertion pain.

PMID- 7628205
TI  - Pregnancy among Hispanic teenagers: is good parental communication a deterrent?
AB  - Effective communication between Hispanic parents and teens about sexual issues
      may deter adolescent pregnancy, yet little is known about the prevalence or
      impact of such communication. The study examined this potential relationship in a
      cohort of urban Hispanic adolescents. A questionnaire was administered to a non
      random sample of pregnant and non-pregnant Hispanic women aged 12-18 years
      attending inner city schools in Los Angeles to obtain demographic, sexual
      activity and communication information. Logistic regression analysis was used to
      evaluate the independent contribution of risk factors to teenage pregnancy. Good
      communication with one's mother was inversely related to pregnancy; the adjusted
      odds ratio of pregnancy if the mother told the daughter about sex was 0.3 (95% CI
      0.2-0.6). Friends' love was also inversely related to pregnancy (odds ratio 0.7;
      95% CI 0.6-0.8). In order of increasing strength, alcohol and drug use, favorable
      attitude toward premarital sex, receipt of welfare, older age at menarche, and
      older age were all significantly related to pregnancy. Pregnant Hispanic
      teenagers have poorer communication with their parents than do other Hispanic
      teens. Efforts to reduce the incidence of adolescent pregnancy among Hispanics
      may need to address not only family communication but also issues outside the
      home such as alcohol and recreational drugs.

PMID- 7628207
TI  - Biological activity in the repopulating rat spermatocyte after the withdrawal of
      gossypol treatment. V. Inhibition and recovery of microtubular dynein.
AB  - After oral administration with gossypol acetic acid for various times, young male
      rats developed a low content of microtubular (or cytoplasmic) dynein in the
      spermatogenic cells, e.g., spermatids and primary spermatocytes. The content of
      dynein in the cells was measured by enzyme-linked immunosorbent assay (ELISA)
      using monoclonal anti-dynein antibody. The results were expressed as ng
      dynein/10(6) cells and compared with those of the control rats. After gossypol
      treatment for 8, 12, and 19 weeks, the content of dynein in spermatids was
      reduced by 61%, 70%, and 68%, respectively; whereas, the amount of dynein in
      primary spermatocytes was reduced by 37%, 44%, and 31%, respectively. The
      microtubular dynein associated with spermatids was more vulnerable to gossypol
      than that of the primary spermatocytes. Immunofluorescent staining technique
      confirmed the finding that the control cells have more dynein than that of the
      drug-treated cells. Eight weeks after the withdrawal of the drug treatment, the
      content of dynein in spermatids and primary spermatocytes was fully recovered.
      The possible effects of this change in conjunction with the function of
      microtubules during spermatogenesis and sperm motility are discussed.

PMID- 7628206
TI  - A comparative study on the return to ovulation following chronic use of once-a
      month injectable contraceptives.
AB  - A comparative study was undertaken involving 21 Mexican women who discontinued
      the use of medroxyprogesterone acetate 25 mg plus oestradiol cypionate 5 mg
      (Cyclofem) and norethisterone enanthate 50 mg plus oestradiol valerate 5 mg
      (Mesigyna) to assess the time required for the return to menses and ovulation.
      All subjects were exposed to once-a-month injectable contraceptives for two years
      and were followed for 120 days after the last injection. The urinary
      concentration of oestrone glucuronide and pregnanediol glucuronide was determined
      daily in all subjects beginning one month after the last injection. The results
      disclosed that ovulatory cycles were documented after 120 days of the last
      injection in six women of each studied group. Similar endometrial bleeding
      patterns were observed in both groups, indicating that the two drugs have alike
      pharmacokinetic and pharmacodynamic effects.

PMID- 7628208
TI  - Acrosin inhibitor, 4'-acetamidophenyl 4-guanidinobenzoate, an experimental
      vaginal contraceptive with anti-HIV activity.
AB  - Serine proteases are involved in a wide variety of seemingly unrelated
      physiological functions including capacitation of the spermatozoa and
      potentiation of human immunodeficiency virus (HIV) infection. The experimental
      vaginal contraceptives derived from 4-guanidinobenzoic acid act through
      inhibition of acrosin--a serine protease from the sperm. The serial ten-fold
      dilutions of 4'-acetamidophenyl 4-guanidinobenzoate (AGB) were tested in vitro
      for the effect against HIV infection by assaying the suppression of de novo p24
      synthesis in virus-inoculated MT-4 T lymphocytes. The results reveal that
      complete inhibition of HIV occurred at 100 micrograms/ml--a dose corresponding to
      previously reported concentrations responsible for preventing fertilization in
      rabbits. These findings suggest that serine protease inhibitors and in particular
      the guanidinobenzoates, reported to be up to 100-fold more potent and less
      irritating than nonoxynol-9, can be potentially operative against sexual
      transmission of HIV.

PMID- 7628209
TI  - The costs of critical illness to families.

PMID- 7628210
TI  - Article doesn't reflect today's Army field healthcare system.

PMID- 7628211
TI  - Readers express concerns with critical care technicians.

PMID- 7628212
TI  - Critical Care Family Needs Inventory: a cognitive research utilization approach.

PMID- 7628213
TI  - Acute pancreatitis: an Orem approach to nursing assessment and care.

PMID- 7628214
TI  - Management of cerebral oxygen supply-demand balance in blunt head injury.

PMID- 7628215
TI  - Femoral artery pseudoaneurysm after invasive procedures.

PMID- 7628216
TI  - Clinical exemplars: one group's experience.

PMID- 7628217
TI  - Support group for families of trauma patients: a unique approach.

PMID- 7628218
TI  - Self-instructional modules: a strategy for teaching the 12-lead ECG.

PMID- 7628219
TI  - Terry Richmond: trauma--beyond the hospital for patients and families. Interview
      by Michael Villaire.

PMID- 7628220
TI  - The patient-driven system.

PMID- 7628221
TI  - Florence Nightingale: a message for today.

PMID- 7628222
TI  - Managing sedation in the critically ill patient.

PMID- 7628223
TI  - Relative utilization of reptiles and rodents as hosts by immature Ixodes
      scapularis (Acari: Ixodidae) in the coastal plain of North Carolina, USA.
AB  - The interaction of immature black-legged ticks, Ixodes scapularis, with reptiles
      and rodents was investigated in various woodland habitats in the coastal plain of
      North Carolina. Reptiles were sampled from April 1 to September 30, 1991. No
      ticks were found on 95 specimens representing 16 species of snakes. Ticks were
      found on 54 (36.7%) of 147 lizards. I. scapularis was the only tick recovered
      from lizards. Some lizards were collected in drift fence traps each month of the
      study except August. Capture rates averaged one lizard per 16 trap-days. Larvae
      and nymphs of I. scapularis were removed from the southeastern five-lined skink
      (Eumeces inexpectatus), the ground skink (Scincella lateralis), the broad-headed
      skink (E. laticeps) and the eastern glass lizard (Ophisaurus ventralis), but
      ticks were not found on three other lizard species. Tick infestation rates and
      loads for parasitized species are presented. Ticks were almost exclusively
      attached at the base or in the axils of forelimbs of skinks and in the lateral
      grooves of eastern glass lizards. Rodents were live-trapped at sites where
      lizards were sampled and at other sites from 1 July, 1990 to 30 January, 1992.
      Capture rates averaged one rodent per 47 trap-nights. Ticks were found on 23
      (17.8%) of 129 animals inspected. Five species of rodents were examined but only
      four species were found to be tick-infested. In contrast to lizards, few I.
      scapularis were collected. Rodents, principally the white-footed mouse
      (Peromyscus leucopus) and cotton mouse (P. gossypinus) were most frequently
      infested with immature American dog ticks, Dermacentor variabilis, during winter
      and early spring months. Burdens of D. variabilis on these rodents averaged 0.3
      ticks per rodent. Effects of the diversion of ticks from feeding on Peromyscus
      mice on the transmission of the Lyme disease spirochete are discussed.

PMID- 7628224
TI  - Small and medium sized mammals as predators of ticks (Ixodoidea) in South Africa.
AB  - A total of 1,640 stomach contents from 56 South African species of small and
      medium sized mammals were examined for ticks. Only six ticks were found in three
      specimens of the caracal Felis caracal. Although identification of the tick
      species was not possible owing to fragmentation and partial digestion, the genus
      Haemaphysalis was represented in four of these cases. We conclude that predation
      by small and medium sized mammals on ticks is uncommon in South Africa.

PMID- 7628225
TI  - Rhipicephalus sanguineus: observations on the parasitic stage on dogs in the
      Negev Desert of Israel.
AB  - Sixteen dogs were studied for infestation with R. sanguineus in Kibbutz Ze'elim
      in the northwestern part of the Negev Desert over a period of one year. The mean
      number of ticks per dog per month was 16.4. The majority of the ticks were
      adults: males (48.6%) and females (34.4%). The ears and abdomen of the dog were
      the predilection sites for the ticks. Male ticks were more abundant on the ears,
      whereas female ticks were more abundant on the ears and the abdomen. A strong
      correlation between tick numbers and the ambient temperatures was found. The mean
      percentage of dogs infested in the winter months was 16.6% and increased in the
      summer months to 34.4%. During winter, ticks were found more often on the ears
      and head of their hosts whereas in summer they were distributed mainly on the
      ears, head and abdomen. The male:female ratio was higher in winter (2.3:1) than
      in summer (1.1:1).

PMID- 7628226
TI  - Correlation between antibodies to Cowdria ruminantium (rickettsiales) in cattle
      and the distribution of Amblyomma vector ticks in Zimbabwe.
AB  - Cowdriosis, caused by Cowdria ruminantium, is transmitted by Amblyomma ticks,
      which are widely distributed in Zimbabwe. To assess the distribution of this
      disease in Zimbabwe, cattle either exposed to Amblyomma ticks or maintained in
      areas free from these ticks were tested for antibodies to Cowdria. A total of 324
      sera were tested using competitive ELISA and the indirect fluorescent antibody
      test (IFAT). At diptanks in Amblyomma-infested areas 52% (n = 95) and 26% (n =
      47) of sera were positive by cELISA and IFAT, respectively. At diptanks in
      Amblyomma-free areas 11% (n = 125) and 10% (n = 134) of sera were positive by
      cELISA and IFAT, respectively. The results were significantly different between
      Amblyomma-infested and tick-free areas (chi 2 = 24.73, P < or = 0.005 for IFAT
      and chi 2 = 57.53, P < or = 0.005 for cELISA). High background readings in field
      sera, possibly due to cross-reactive antibodies to Ehrlichia spp., complicated
      the determination of a realistic cut-off point, especially in cELISA. On the
      basis of the distribution of Amblyomma ticks, currently a large part of Zimbabwe
      can be considered endemic for the disease.

PMID- 7628227
TI  - Pathogenicity of 17 isolates of entomophagous nematodes (Steinernematidae and
      Heterorhabditidae) for the ticks Amblyomma variegatum (Fabricius), Boophilus
      microplus (Canestrini) and Boophilus annulatus (Say).
AB  - Entomopathogenous nematodes are well known biocontrol agents of insects. They
      live in the superficial layer of the soil, a location where ticks accomplish
      their molt and where they oviposit their eggs, making them, theoretically, the
      preys of infective larvae of nematodes. Seventeen strains of entomopathogenous
      nematodes: eight strains of Steinernema and nine strains of Heterorhabditis were
      placed in contact with each of the free living stages of three tick species:
      Amblyomma variegatum, Boophilus microplus and B. annulatus. The first two species
      were resistant to all the nematode strains that were tested, whereas B. annulatus
      was susceptible to all of them. Ovipositing females were more susceptible than
      females during the preoviposition period. There were no anatomical differences
      between the two species of Boophilus which can account for such differences in
      their susceptibility. The use of nematodes to control some species of ticks
      should be considered.

PMID- 7628228
TI  - Detection of the protozoan parasite Theileria annulata in Hyalomma ticks by the
      polymerase chain reaction.
AB  - Adult Hyalomma ticks were examined for the presence of Theileria annulata
      infection using the Polymerase Chain Reaction (PCR). A 372 bp DNA fragment
      derived from the small ribosomal RNA gene of T. annulata was amplified from 45
      out of 50 (90%) H. dromedarii ticks and from 36 out of 50 (72%) H. marginatum
      marginatum ticks. No product was amplified from non-infected control ticks.
      Restriction enzyme digestion with Sac II confirmed that the product was derived
      from the targeted T. annulata gene. As a further confirmation it was shown that
      both species of Hyalomma ticks were able to transmit T. annulata to experimental
      calves. PCR detection of Theileria parasites in ticks was compared with
      conventional staining of dissected salivary glands using methyl green pyronin and
      its comparative advantages are discussed.

PMID- 7628229
TI  - The appetence behaviour of two South African paralysis-inducing ixodid ticks.
AB  - The appetence responses of the ixodid ticks Ixodes rubicundus and Rhipicephalus
      punctatus to various stimuli were quantified under laboratory conditions. A
      greater percentage of I. rubicundus generally responded to the different stimuli
      at lower than at higher temperatures while the converse was usually true for R.
      punctatus. Radiation heat and shadowing evoked a response in the greatest
      percentage of I. rubicundus, whereas CO2 and host odour were responsible for a
      similar reaction in R. punctatus. A single perturbation of the substrate caused
      more than 50% of I. rubicundus to respond while constant perturbation resulted in
      a progressive decrease in the proportion of ticks reacting. Significantly more R.
      punctatus than I. rubicundus were attracted to a CO2 trap and the R. punctatus
      were also attracted to the trap over a greater distance. Significantly more older
      than younger ticks of both species responded to the various stimuli.

PMID- 7628230
TI  - Evaluating the economic damage threshold for bont tick (Amblyomma hebraeum)
      control in Zimbabwe.
AB  - Controlling ticks and tick-borne diseases by frequent applications of acaricides
      (e.g., dipping) is costly, and can leave treated livestock vulnerable to
      epizootics of tick-borne diseases should the system of applying acaricides break
      down. The concept of only applying acaricides on an infrequent (strategic) basis
      often relies on the target tick population displaying a seasonal cycle. However,
      as adult bont tick (Amblyomma hebraeum) infestations in Zimbabwe's lowveld do not
      have a strictly seasonal pattern of occurrence, it is recommended that tick
      control only be applied when bont tick infestations are equal to, or greater
      than, their economic damage threshold. The economic damage threshold is the
      minimum average weekly standard female tick burden sufficient to cause damage
      equal in dollar value to the costs of applying tick control. Assuming that each
      standard female tick represents a 10 gram weight loss, the economic damage
      threshold (standard female ticks/week) is equivalent to the ratio of the producer
      price of beef (liveweight equivalent): per head cost of dipping (Eqn (3)). To
      illustrate the application of the threshold methodology, it was assumed that the
      producer price of beef was Z$1.63/kg (U.S.$0.33/kg) and that tick control cost
      Z$0.29/hd/dip (U.S.$0.06/hd/dip). This gave a threshold of 18 standard female
      ticks/head/week. Using tick counts obtained from 20 Brahman cattle held at Mbizi
      in southeastern Zimbabwe, it was shown that for the 1988 calendar year there were
      only 32 weeks when the economic damage threshold was met or exceeded. This is
      substantially less that the 44 dippings per year that have been, until very
      recently, legally required in Zimbabwe. Sensitivity analysis showed that a 10%
      rise in the cost of dipping reduced to 23 (a 28% decrease) the number of weeks
      when tick burdens exceeded the economic damage threshold. By further assuming
      that an acaricide application and residual effects will cause a 3-5 week interval
      before the next application may be required, the number of weeks when the tick
      burden was equal to or greater than the threshold of 18 standard females/week
      fell to just 9-12 weeks. Three factors may cause an alteration in the economic
      damage threshold: i) tick burdens may cause damage to the udders; ii) secondary
      infestations (e.g., screw-worm) may cause economic damage; and iii) nutritional
      stress of the cattle may reduce the actual average per tick weight loss.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7628231
TI  - The effect of inflammatory and hypersensitive reactions, in response to the
      feeding of the tick Amblyomma variegatum, on the progression of experimental
      dermatophilosis infections.
AB  - Initial infestations of Amblyomma variegatum larvae and nymphs, on rabbits and
      sheep respectively, produced inflammatory reactions in the host's skin; repeated
      infestations resulted in an increase in development of delayed type
      hypersensitive reactions. Dermatophilus congolensis cocci were applied in
      titrated doses to hosts at sites of inflammatory or hypersensitive reactions to
      ticks, and to control hosts with no exposure to ticks. We assessed the resulting
      infections for three weeks and found no significant difference between the
      infections on the three groups. We conclude that the local effects of the feeding
      of immature stages of this tick do not influence the pathogenesis of
      dermatophilosis.

PMID- 7628232
TI  - The localization of a paralysis toxin in granules and nuclei of prefed female
      Rhipicephalus evertsi evertsi tick salivary gland cells.
AB  - A monoclonal antibody directed against a paralysis toxin of Rhipicephalus evertsi
      evertsi ticks was used to localize the toxin in cytoplasmic granules and,
      surprisingly, chromatin of the nuclei of cells which resemble the "b" cell type
      in the salivary glands of Rhipicephalus appendiculatus, Boophilus microplus and
      Ixodes holocyclus. The association of toxin with chromatin indicates that the
      toxin may have a regulatory function. Evidence is provided to support the view
      that the toxin is made up of three identical sub-units, with only the trimeric
      form being toxic.

PMID- 7628233
TI  - Investigations into lymphocyte transformation and histamine release by basophils
      in sheep repeatedly infested with Rhipicephalus evertsi evertsi ticks.
AB  - The immune response of a natural host of Rhipicephalus evertsi evertsi to feeding
      by this tick species was investigated with respect to the effects of tick
      salivary gland extracts on the transformation of peripheral blood lymphocytes and
      the release of histamine by basophils obtained from repeatedly infested sheep.
      The results indicated that there was no stimulation of lymphocyte transformation
      but that histamine release was elevated 10 fold after four infestations. Although
      this suggests a hypersensitivity reaction, believed to be a major factor in
      resistance to tick feeding, it was observed that ticks fed normally even after
      four infestations with 28 day intervals in between. These results emphasize the
      adaptation of ticks to feeding on their natural hosts.

PMID- 7628234
TI  - Ability of transovarially and subsequent transstadially infected Ixodes hexagonus
      ticks to maintain and transmit Borrelia burgdorferi in the laboratory.
AB  - In a previous study, transstadial and transovarial survival of Borrelia
      burgdorferi in Ixodes hexagonus and transmission to laboratory mice via the bite
      of infected females were demonstrated. Here, we report the ability of I.
      hexagonus progeny infected transovarially to maintain and transmit the
      spirochaete to the host. Ticks were examined for spirochaetes by direct
      immunofluorescence antibody test. I. hexagonus larvae derived from the parental
      transstadially infected females were fed on two white mice: 21/54 (38.9%) of
      these ticks examined as unfed nymphs were infected. I. hexagonus nymphs were fed
      on three white mice and examined for spirochaetes after moulting as adults: 7/25
      (28%) were found to harbour the spirochaete. The success of B. burgdorferi
      transmission to the mice by larval and nymphal I. hexagonus was determined by
      xenodiagnosis using I. ricinus larvae: 20/50 (40%) and 30/99 (30.3%) of the I.
      ricinus larvae fed on the mice infected by I. hexagonus larvae and nymphs
      respectively became infected. This study shows that B. burgdorferi can be
      maintained through transovarial and subsequent transstadial transmissions in I.
      hexagonus.

PMID- 7628235
TI  - The local effect of hypersensitive or inflammatory reactions to nymphal Amblyomma
      variegatum on simultaneous infections with Dermatophilus congolensis.
AB  - Amblyomma variegatum nymphs were applied to sites infected with Dermatophilus
      congolensis on eight rabbits. Four rabbits were previously sensitized to the
      feeding of nymphal A. variegatum to produce hypersensitive reactions to the tick
      feeding; the remaining four rabbits had no previous exposure to nymphal A.
      variegatum and produced inflammatory reactions to the tick feeding. The resulting
      dermatophilosis infections were assessed for three weeks and there was a
      correlation between the position of the inflammatory tick attachment sites and
      the foci of infection. There was a significant increase in the lesions at sites
      with inflammatory reactions to the ticks, compared with sites not exposed to tick
      feeding; these differences appeared to be due to individual variation in the host
      response and were not sustained throughout the assessment.

PMID- 7628236
TI  - Oxygen consumption of engorged nymphs and unfed adults of Hyalomma asiaticum
      ticks (Acari: Ixodidae) exposed to various photoperiods.
AB  - The oxygen consumption of engorged nymphs of Hyalomma asiaticum was measured at
      various intervals after drop-off from mice hosts. Duration of nymphal development
      to the emergence of adults was 25-32 days at 25 degrees C. The oxygen consumption
      was high immediately after completing the blood meal (193-248 mm3 g-1 h-1 but
      decreased significantly 18 days later (at 25 degrees C) to 45-65 mm3 g-1 h-1. It
      increased again before ecdysis (81-102 mm3 g-1 h-1, and also after ecdysis in
      freshly moulted adults (177-220 mm3 g-1 h-1. The oxygen consumption in 8-month
      old adult ticks was very variable ranging from 40-42 to 172 mm3 g-1 h-1. Neither
      engorged nymphs nor unfed adult ticks showed any dependence of their respiratory
      metabolism on the photoperiodic regimes tested (LD 20:4 and LD 12:12, with or
      without transfer to an alternative photoperiod after engorgement of nymphs).

PMID- 7628237
TI  - Ticks (Acari: Ixodidae) infesting the Arabian camel (Camelus dromedarius) in the
      Sinai, Egypt with a note on the acaricidal efficacy of ivermectin.
AB  - In this study, tick burdens on camels (Camelus dromedarius) were determined in
      the vicinity of the St. Catherine monastery, Sinai, Egypt. In total 2,545 ticks
      (1,491 adults and 1,054 nymphs) were collected and identified. Mean tick burdens
      were relatively heavy and the range in number of ticks per camel was very broad
      (6-173). Hyalomma dromedarii was the predominant tick species and accounted for
      95.6% of the adult ticks. Other ticks found were H. marginatum subspp. and H.
      anatolicum excavatum. All nymphs collected were Hyalomma spp. In addition, the
      effect of ivermectin (Ivomec MSD AGVET) on tick burdens, when given
      subcutaneously at 0.2 mg/kg-1, was evaluated in nine camels in the date-palm
      plantation of Kibbutz Yahel in the Arava valley, Israel. Initial tick burdens on
      these camels (half-body tick counts) ranged from 20-105 ticks per camel. Seven
      camels from the same herd with half-body tick counts ranging from 40-107 ticks
      per camel were not treated and served as a control group. Ivermectin was not
      effective against Hyalomma tick infestation in camels under these conditions.

PMID- 7628238
TI  - Sexual dimorphism in nymphal size of the Karoo paralysis tick, Ixodes rubicundus.

PMID- 7628239
TI  - Ability of successful attack in two species of ixodid ticks (Acari: Ixodidae) as
      a manifestation of their aggressiveness.
AB  - Patterns of attacking hosts by two closely related species of ixodid ticks
      (Ixodes persulcatus and I. ricinus) were compared in parallel field tests. The
      ability of active unfed adults of both sexes to adhere to a flannel flag dragged
      over grass vegetation and to remain on the flag during this process were
      estimated. The tests were conducted under two temperature conditions, 6-10
      degrees C and 17-22 degrees C. In all test versions, adults of I. persulcatus
      were more successful both in adhering to the flag and in remaining on it. There
      were no consistent differences between males and females of the same species. The
      results demonstrated a differing ability of successful attack in both tick
      species. This ability is a complex derivative of the tick activity and
      aggressiveness. An attempt is made to analyse the latter phenomenon, which is
      considered as a general one for all bloodsucking arthropods. The aggressiveness
      of arthropods should be taken into account as one of the leading factors
      influencing the sampling results.

PMID- 7628240
TI  - Pheromonal composition of two species of African Amblyomma ticks: similarities,
      differences and possible species specific components.
AB  - Two species of bont ticks, Amblyomma hebraeum and Amblyomma variegatum, common to
      Africa were studied to compare types and quantities of compounds known or
      believed to serve as components of the attraction-aggregation-attachment
      pheromone (AAAP). A complex of attraction, aggregation and attachment stimulating
      pheromone components are used by these ticks to detect hosts, mates and, perhaps,
      minimize interspecific breeding. Solvent extraction of pheromone emitting ticks
      followed by gas chromatography and mass spectrometry revealed little qualitative
      difference in the composition of the AAAP in these two species. However, subtle
      differences in the relative proportions of the pheromonal blend are noted
      suggesting that such differences in concentration may facilitate species-specific
      discrimination during aggregation and attachment. Differences in the relative
      abundance of benzaldehyde and methyl salicylate in the males of the two species
      were especially noteworthy. Possible means by which such differences in phenolic
      compound composition may affect the behavior of these ticks are discussed.

PMID- 7628241
TI  - Vertical migration of adult Ixodes rubicundus, the Karoo paralysis tick (Acari:
      Ixodidae).
AB  - Mortality due to Karoo paralysis amongst livestock is of considerable economic
      importance in South Africa. Indications are that the extent of vertical migration
      of adult ticks, to reach questing positions on grasses, is influenced by sudden
      climatic changes. Such influences as well as selection of questing substrates
      were investigated under controlled conditions. Vertical migration of adult Ixodes
      rubicundus on copper rods was determined in a square metal arena within a closed
      glass container in a room in which temperature and light could be controlled.
      Significantly more female and male ticks migrated vertically on 1.5 mm diameter
      rods than on 4.0 mm rods and on 450 mm long rods than on 100 mm rods. More ticks
      of both sexes migrated vertically at RH > 80% than at RH < 50% and at 12 degrees
      C than at 21 degrees C. More female than male and more older than younger ticks
      migrated vertically in all experiments. The results of this study contribute
      towards an understanding of the epidemiology of Karoo paralysis.

PMID- 7628242
TI  - Localization of insulin-like immunoreactivity in the synganglion of nymphal and
      adult Dermacentor variabilis (Acari: Ixodidae).
AB  - Immunocytochemical staining based on a peroxidase-antiperoxidase method showed
      neurosecretory cells (NSC) reactive to bovine insulin in five of 18 paraldehyde
      fuchsin-positive neurosecretory regions (NSR) in the synganglion of unfed adult
      Dermacentor variabilis. This is the first report of a neuropeptide in an ixodid
      tick. The insulin-specific immunoreactive cells included the posterior medial
      group of the protocerebral center, posterior group of dorsal opisthosomal center,
      anterior lateral group of the dorso-lateral cheliceral center, dorsal group of
      the frontal stomodeal center, and anterior group of the ventral palpal center.
      After feeding and mating, females no longer had immunoreactive cells in three of
      five NSR found in virgin, unfed females. However, two cells of the posterior
      group in dorsal opisthosomal center and anterior lateral group of the dorso
      lateral cheliceral center remained immunoreactive throughout feeding. Fed, mated
      males continued to display immunoreactive cells in four of five NSR found in the
      virgin, unfed males. All developmental stages of nymphs examined had insulin
      specific immunoreactive cells in two of the five NSR found in unfed adults,
      including two positively stained cells of the posterior group in dorsal
      opisthosomal center and anterior group of ventral palpal neurosecretory center.

PMID- 7628243
TI  - The effect of feeding immature Karoo paralysis ticks Ixodes rubicundus (Acari:
      Ixodidae) on the metabolic rate of the rock elephant shrew.
AB  - The effect of feeding immature Karoo paralysis ticks (Ixodes rubicundus) on the
      resting metabolic rate (RMR) of their principal natural host, the rock elephant
      shrew (Elephantulus myurus), was investigated under laboratory conditions. The
      elephant shrews were artificially infested with numbers of ticks simulating
      natural burdens. The RMR of the elephant shrews was quantified by measuring the
      oxygen consumption in an open through-flow system. The RMR of hosts infested only
      with larvae did not differ from that of the control group. Those infested with
      nymphs, or nymphs and larvae, had significantly lower RMR's compared to the
      control animals. There were no signs of paralysis in any of the infested hosts.

PMID- 7628244
TI  - Comparative reproduction and nonparasitic development of Boophilus microplus and
      hybridized Boophilus ticks (Acari: Ixodidae) under natural field conditions in
      subtropical south Texas.
AB  - The reproductive biology and nonparasitic development of Boophilus microplus
      (Canestrini) and hybridized Boophilus ticks (B. annulatus (Say) male x B.
      microplus female) held under natural field conditions in south Texas throughout
      the year were compared. Comparisons between the two types of ticks indicated that
      the ovipositional biology (percentage of ovipositing females and number of eggs
      laid) of the females favored hybrid ticks during some months and B. microplus
      ticks during other months. However, on a year long basis, there was virtually no
      difference in the percentage of ovipositing females or in the number of eggs
      deposited by hybrid females as compared to B. microplus. The duration of each
      nonparasitic development period (preoviposition period, incubation period of
      eggs, and larval longevity) showed that both types of ticks had very similar
      developmental and survival rates during the year. Generally the difference in
      duration of each of the nonparasitic parameters was < 8 days, leading to a high
      degree of synchrony of the nonparasitic developmental rates between the two types
      of ticks. On the other hand, egg hatchability of hybrid ticks was consistently
      lower than pure-strain B. microplus throughout the year with significantly lower
      hatch rates occurring in April, July, August, October, and November. Thus,
      results obtained on percentage of ovipositing females, number of eggs laid,
      preoviposition period, incubation period of eggs, and larval longevity provide
      encouragement for the possible use of sterile hybrid males as a means of
      eliminating a native B. microplus population. In contrast, results of the egg
      hatchability of the two types of ticks indicate that the selective advantage
      afforded to B. microplus could have an adverse affect on the success of a sterile
      hybrid male program by making the number of hybrid ticks necessary to eliminate a
      native population prohibitively high.

PMID- 7628245
TI  - Susceptibility of the taiga tick Ixodes persulcatus Schulze to pyrethroids.
AB  - The susceptibility of the taiga tick Ixodes persulcatus Schulze to 15 pyrethroids
      has been evaluated. The knockdown time after exposure of ticks to pyrethroids
      tested was quite similar. It was revealed that the lethal doses of type I
      pyrethroids (permethrin-like) induced the rapid attachment of ticks to host. In
      contrast, the fatal poisoning with type II pyrethroids (alpha-CN-pyrethroids)
      made the ticks unable to attach completely. Possible mechanisms of the
      acceleration and the prevention of attachment are discussed.

PMID- 7628246
TI  - Cuticular hydrocarbon composition and phenotypic variability in sympatric
      populations of Ixodes ricinus ticks from Poland.
AB  - Gas chromatography of cuticular hydrocarbons was used to assess genetic
      similarity and heterozygosity between 18 sympatric populations of adult Ixodes
      ricinus ticks collected from Poland. Sixteen n-alkanes, 45 monomethylalkanes, and
      36 dimethylalkanes were identified. Forty-one compounds were detected in 90% of
      the specimens and nine hydrocarbons were present in all the specimens studied.
      Visual inspection of chromatograms revealed major differences in the relative
      abundance of hydrocarbons between populations of I. ricinus. The average
      proportion of heterozygotic hydrocarbons was 50.68%, while the average genetic
      similarity among all populations was 0.967. Two other methods were used to
      measure the intrapopulation variability: the number of isomeric forms for each
      hydrocarbon and the range of hydrocarbon abundance. It was found that some
      hydrocarbons manifested an unexpectedly high number of isomeric patterns, such as
      nonacosane (21 patterns), triacontane (23), pentacosane (26), and hexacosane
      (28). Our data suggest that I. ricinus ticks from Poland consist of several
      interbreeding, non-isolated populations, with a high degree of genetic flow
      between them.

PMID- 7628247
TI  - Cholesteryl esters on the body surfaces of the camel tick, Hyalomma dromedarii
      (Koch, 1844) and the brown dog tick, Rhipicephalus sanguineus (Latreille, 1806).
AB  - Cholesteryl esters were found to constitute a major component of the lipids
      coating the body cuticle of females of the camel tick, Hyalomma dromedarii and
      the brown dog tick, Rhipicephalus sanguineus. One or more cholesteryl esters,
      alone or in combination, have been shown to serve as the mounting sex pheromone
      of several species of ixodid ticks. Consequently, knowledge of these compounds is
      important for an understanding of the mating behavior of these ticks. Based on
      thin layer chromatography, cholesterol and cholesteryl esters were the most
      abundant neutral lipids found on the body surfaces of fed females of these two
      species. Analysis using HPLC demonstrated significant quantities of the following
      compounds, tentatively identified as cholesteryl esters (expressed in micrograms
      per female equivalent), in H. dromedarii: Cholesteryl acetate 18.2; cholesteryl
      laurate, 6.8; cholesteryl linoleate, 24.8; cholesteryl oleate, 12.9; cholesteryl
      palmitate, 0.3; and cholesteryl stearate 1.7. In contrast, the same method
      revealed only 3 cholesteryl esters in extracts of females of R. sanguineus:
      Cholesteryl acetate, 2.0; cholesteryl linoleate, 8.5; and cholesteryl oleate,
      3.0. In both species, two unidentified peaks, with the spectral characteristics
      of cholesteryl esters, were also observed. Identification of the cholesteryl
      esters was confirmed: by (1) positive bioassay results with conspecific (H.
      dromedarii) males and heterospecific (Dermacentor variabilis) males; (2)
      similarity of ultraviolet spectra between identified sample peaks and authentic
      standards; and (3) demonstration of cholesterol and the corresponding free fatty
      acid following enzymatic digestion of each of the HPLC-separated fractions
      containing the different cholesteryl esters. Comparisons with the cholesteryl
      ester composition of the mounting sex pheromone of other metastriate Ixodidae are
      discussed. These findings, along with studies reported previously, suggest that
      differences in the mounting sex pheromones of ixodid ticks are an important
      factor in minimizing heterospecific matings in nature.

PMID- 7628248
TI  - Immunisation of rabbits against the brown ear tick, Rhipicephalus appendiculatus
      using tick haemolymph.
AB  - Tick naive rabbits were immunised with haemolymph components from partially fed
      Rhipicephalus appendiculatus adult ticks and subsequently challenged with all the
      developmental instars of the tick. The results obtained showed that the rabbits
      were rendered resistant to all the instars of the tick. However, the resistance
      was more pronounced in adult ticks than in the immature stages. The resistance
      was manifested as a reduction in the number of ticks that fed successfully to
      engorgement, reduced engorgement weights and reduced fecundities. Re challenging
      the resistant experimental rabbits with all the developmental instar stages of
      Rhipicephalus appendiculatus showed that resistance was maintained in subsequent
      infestations.

PMID- 7628249
TI  - Transient expression of a Drosophila melanogaster hsp70 promoter/lacZ construct
      injected into larvae of two species of predatory mites (Acari: Phytoseiidae).
AB  - The Drosophila melanogaster heat shock 70 promoter (hsp70) was used to regulate
      expression of the Escherichia coli beta-galactosidase gene (lacZ) in transiently
      transformed predatory mite larvae. A construct containing the hsp70 promoter
      upstream of the D. melanogaster alcohol dehydrogenase (adh) translational start
      site and Escherichia coli lacZ gene fusion (adh/lacZ) was injected into larvae of
      Metaseiulus occidentalis and Amblyseius finlandicus. LacZ expression was compared
      to expression of a similar construct lacking any upstream regulatory sequence.
      Expression from the hsp70 promoter was strong and heat shock-dependent in both
      species. The Drosophila hsp70 promoter therefore appears useful for regulating
      expression of exogenous DNA in both phytoseiid species and may be broadly
      applicable in the Phytoseiidae. Furthermore, the lacZ gene is a useful gene for
      analysis of expression in both species. Larval microinjection provides a method
      of assessing transient expression and of examining native regulatory sequences in
      these two phytoseiids and will likely be useful in other phytoseiid mites with
      only minor modifications.

PMID- 7628250
TI  - Transmission of injected DNA sequences to multiple eggs of Metaseiulus
      occidentalis and Amblyseius finlandicus (Acari: Phytoseiidae) following maternal
      microinjection.
AB  - The persistence of DNA injected into two species of adult female phytoseiids and
      its transmission to serial eggs deposited by them was assessed by the polymerase
      chain reaction (PCR). The effect of DNA concentration on persistence and
      transmission was examined in Metaseiulus occidentalis. M. occidentalis females
      were microinjected with plasmid DNA at three different concentrations (250, 500,
      750 ng microL-1) and allowed to deposit one to five eggs before the females and
      their last eggs were analyzed. Plasmid DNA was found in 82% of the females
      assayed and in 70% of all the eggs analyzed (including the fifth eggs produced
      after microinjection). Transmission of DNA to multiple eggs was also examined in
      Amblyseius finlandicus. Females of this species are less traumatized by
      microinjection allowing analysis of transmission over a more extended number of
      eggs. Females were microinjected and allowed to deposit eggs until their death.
      DNA from every fifth egg was analyzed by the PCR. PCR products were amplified
      from 51% of the eggs and from all egg classes except the 30th egg. The
      persistence and presence of plasmid DNA in both eggs and females suggests that
      (1) maternal microinjection is a more efficient method for DNA delivery than
      traditional egg microinjection, (2) it may be possible to isolate transformants
      from fewer maternally-microinjected females than originally expected, and (3)
      maternal microinjection could be useful as a DNA delivery system in other
      phytoseiids.

PMID- 7628251
TI  - Evidence for a mounting sex pheromone in the brown ear tick Rhipicephalus
      appendiculatus, Neuman 1901 (Acari: Ixodidae).
AB  - The presence of a mounting sex pheromone was demonstrated on the surface of fed
      female Rhipicephalus appeniculatus. This pheromone, which is present on the
      female cuticle, allows the male to recognise the female. The pheromone was
      removed by cleaning the female in hexane, resulting in the loss of male mating
      behaviour in in vitro experiments. Male mating behaviour was resumed when extract
      made from fed female cuticle was replaced on cleaned females. When the extract
      was transferred to inanimate objects typical male mating behaviour was released.
      Preliminary chemical analyses indicated that the active component of the extract
      was contained in the sterol ester fraction of the extract.

PMID- 7628252
TI  - Intraspecific diversity of the Cassava green mite Mononychellus progresivus
      (Acari: Tetranychidae) using comparisons of mitochondrial and nuclear ribosomal
      DNA sequences and cross-breeding.
AB  - Intraspecific diversity in Cassava Green Mite Mononychellus progresivus Doreste
      was examined using individuals collected in Benin and the Congo and in Columbia
      and Brazil. Comparisons were based on mitochondrial and ribosomal DNA sequences
      and the results of several cross-breeding experiments. Sequence variation was
      examined in a total of 1139 base pairs (bp) constituting the ITS2 ribosomal DNA
      (805 bp) and a fragment of the Cytochrome Oxidase I (COI) gene (334 bp). Sequence
      divergence is low, ranging from 0% to 2.1% for COI and from 0% to 0.4% for ITS2.
      Inter-strain comparisons have shown that the two African populations appear to be
      identical. They were similar to the Colombian population while the Brazilian
      population was clearly different. The data support the hypothesis of a single
      introduction of the species in the two African populations. Crossing experiments
      have shown partial hybrid sterility, suggesting a genetic incompatibility
      consistent with differences detected by sequence data. The results show the
      usefulness of molecular markers as a tool for determining taxonomic status and
      dispersion paths in spider mites.

PMID- 7628254
TI  - A population model for Dermanyssus gallinae (Acari: Dermanyssidae).
AB  - A model based on a time-varying distributed delay with attrition was developed
      for simulating the population dynamics of the chicken mite Dermanyssus gallinae
      (DeGeer, 1778). The model was parametrised according to cohort life table studies
      conducted under constant temperature conditions and was validated with two
      independent data set obtained in an experimental poultry house. The predicted
      mite densities and the stage-structure of the population corresponded to the
      values observed during experimental periods of 32, and 11 weeks, respectively.
      Temperature and a poultry house-specific density effect were determined to
      control the population development.

PMID- 7628253
TI  - Factors affecting the distributions of the ticks Amblyomma hebraeum and A.
      variegatum in Zimbabwe: implications of reduced acaricide usage.
AB  - The ticks Amblyomma hebraeum and A. variegatum are the main vectors of
      heartwater, a disease of ruminants caused by Cowdria ruminantium, in the
      agricultural areas of Zimbabwe. At present, A. hebraeum is widely distributed in
      the dry southern lowveld, and occurs in at least seven foci in the higher
      rainfall highveld. Amblyomma variegatum occurs in the Zambezi valley and
      surrounding dry lowveld areas in the northwest. The distribution of A. hebraeum
      has changed considerably over the past 70 years, while that of A. variegatum
      appears to have remained fairly static. The distribution patterns of both species
      in Zimbabwe display anomalous features; the ticks occur in areas of lowest
      predicted climatic suitability for survival and development and in areas where
      the densities of cattle, the most important domestic host, are lowest. The only
      factor favouring the survival of the species in the lowveld habitats in which
      they occur is the presence of alternative wildlife hosts for the adult stage.
      Their absence from more climatically favourable highveld habitats appears to have
      been the result of intensive acaricide treatment of cattle over a long period and
      a historic absence of significant numbers of wildlife hosts. Eradication of A.
      hebraeum and A. variegatum by intensive acaricide treatment of cattle can be
      achieved in the absence of significant numbers of alternative hosts, because of
      the long attachment and feeding periods of the adults of these tick species.
      However, eradication becomes impossible when alternative hosts for the adult
      stage are present, because a pheromone emitted by attached males attracts the
      unfed nymphal and adult stages to infested hosts. The unfed ticks are not
      attracted to uninfested hosts, such as acaricide-treated cattle. Regular
      acaricide treatment of cattle is expensive and so, for economic reasons, the
      Government of Zimbabwe is no longer enforcing a policy of strict tick control. It
      is likely that reduced tick control will result in the spread of Amblyomma ticks
      to previously uninfested areas. Added to this, recent introductions of various
      wildlife species to highveld commercial farming areas have created conditions in
      which the ticks could become established in higher rainfall areas. Amblyomma
      hebraeum is more likely to spread than A. variegatum, because its adults
      parasitize a wider range of wildlife hosts (warthogs, medium to large-sized
      antelope, giraffe, buffalo and rhinoceros), whereas adults of A. variegatum
      appear to be largely restricted to one wildlife species (buffalo) in Zimbabwe,
      the distribution of which is now confined to very limited areas of the country,
      as part of foot and mouth disease control measures.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 7628255
TI  - Optimisation of a screening procedure for house dust mite numbers in carpets and
      preliminary application to buildings.
AB  - The relative performances of the mobility and heat escape methods for measuring
      house dust mite numbers in carpet has been evaluated. The optimum method was
      found to be the mobility method for 24 hours at ambient temperatures which
      exhibited a mite collection efficiency of approximately 30%. Measurements in
      three dwellings showed that the method should be applied to carpet at several
      locations in the living room and/or bedrooms as a general sampling procedure, or
      adjacent to loungeroom seating to determine the worst case scenario. Carpets
      using different types of fibre within the same dwelling should be assessed
      separately. For the limited number of dwellings investigated, wool carpets were
      found to exhibit higher mite numbers than nylon carpets, even when the former had
      been insect-resist treated. No house dust mites were found in the wool carpets of
      an office building which was mechanically ventilated and heated and achieved low
      indoor humidities in winter.

PMID- 7628256
TI  - Acquisition of Borrelia burgdorferi by Ixodes ricinus ticks fed on the European
      hedgehog, Erinaceus europaeus L.
AB  - A hedgehog, Erinaceus europaeus, was found to be heavily infested with larval and
      nymphal Ixodes ricinus in a forest park in Co. Galway, Ireland. A large
      proportion of the ticks that engorged and detached were infected with the
      spirochaete, Borrelia burgdorferi, the causative agent of human Lyme borreliosis.
      The identity of these spirochaetes was confirmed by immunofluorescent assay with
      B. burgdorferi-specific monoclonal antibody and by polymerase chain reaction test
      and they were transmitted from the hedgehog to laboratory-reared ticks and from
      the ticks obtained from the hedgehog to gerbils (Meriones unguiculatus). The high
      infection rate of the larvae that fed on the hedgehog in comparison with unfed
      larvae from the same habitat was interpreted as strong evidence that this host
      species is reservoir competent. Since hedgehogs can evidently feed adult ticks as
      well as many immature stages, they may well have an important role in the ecology
      of Lyme borreliosis in some habitats.

PMID- 7628257
TI  - The effect of rainfall on tick challenge at Kyle Recreational Park, Zimbabwe.
AB  - The effect of rainfall pattern on tick challenge was investigated at Kyle
      Recreational Park, Zimbabwe, from 1991 to 1992 using drag and removal plot
      methods to sample environmental tick density. The abundance of adults and nymphs
      of the brown ear-tick Rhipicephalus appendiculatus and larvae of the bont tick
      Amblyomma hebraeum was positively correlated with monthly rainfall, whereas no
      relationship with rainfall was revealed for larval R. appendiculatus, adults of
      the red-legged tick R. evertsi, or larvae of the blue tick Boophilus decoloratus.
      A comparison between 1991 (490 mm rainfall) and the drought year of 1992 (161 mm)
      revealed significant differences in the abundance of R. appendiculatus, A.
      hebraeum, and B. decoloratus. During the wet season, R. appendiculatus adults
      were 2-3 times more numerous in the environment during the higher rainfall year
      of 1991. A. hebraeum larval abundance exhibited a similar pattern to that of R.
      appendiculatus adults, but B. decoloratus larvae were more abundant in the
      drought year of 1992 during both the wet and dry seasons. Comparable tick
      abundance data collected at Kyle during the above-average rainfall years of 1975
      1977 (mean = 1029 mm) were compared with tick challenge during the below-average
      rainfall years of 1991-1992 (mean = 326 mm). In grassland sand habitat and all
      habitats combined R. appendiculatus adults, nymphs, and larvae were much more
      abundant during the high rainfall years. In contrast, larvae of B. decoloratus
      were more numerous during the drier years. A hebraeum larvae were also more
      abundant during the drier years. The strong positive correlation of adult R.
      appendiculatus abundance with rainfall and the coincidence of increased adult
      tick challenge with increased rainfall indicate that adult R. appendiculatus tick
      burden on hosts would be heaviest during the wet season and high rainfall years.

PMID- 7628258
TI  - Infection rates of Borrelia burgdorferi in different instars of Ixodes ricinus
      ticks from the Dutch North Sea Island of Ameland.
AB  - Between 1988 and 1993, a total of 7173 I. ricinus ticks, predominantly, were
      collected from the vegetation on the Dutch North Sea Island of Ameland. A
      proportion of the ticks (n = 547) was screened for the presence of Borrelia by
      immunofluorescence. Infection rates of Borrelia varied, in nymphs (n = 347) from
      13% to 46% and in adults, (n = 122) from 20% to 43%. The infection rate in larvae
      (n = 84) collected in 1993 was 21%, showing that transovarial transmission of B.
      burgdorferi occurs in the I. ricinus population on Ameland. Two tick-naive sheep
      seroconverted for B. burgdorferi after field-collected adult or nymphal I.
      ricinus were allowed to feed on them. Larval progeny (n = 168) of 15 female adult
      ticks fed on one of these sheep were free from B. burgdorferi. B. burgdorferi was
      isolated in culture from field-collected adult ticks. Serotyping using monoclonal
      antibodies against outer surface proteins A and C indicated that both isolated
      belonged to genospecies B. garinii, and this was confirmed by DraI restriction
      analysis of the variable DNA sequence between the 5S and 23S rRNA genes.

PMID- 7628259
TI  - Reproductive interactions between two Australian reptile tick species.
AB  - In South Australia the two tick species Amblyomma limbatum and Aponomma
      hydrosauri share the same common reptile host species, but have allopatric
      distributions which abut along a narrow parapatric boundary. Reproductive
      interference is a mechanism that has previously been suggested could contribute
      to maintaining the boundary. Populations of each species were established in pens
      within the range of Aponomma hydrosauri. Pens held either each species alone, or
      the two species together. The performance of females in those pens was monitored
      over 28 months. There was no indication that the proportion of attached females
      which mated and engorged was reduced by the presence of heterospecifics. There
      was no indication that the time taken to mate, engorge and detach was any longer
      in the presence of heterospecifics. The experiment did not support the hypothesis
      that reproductive interference contributes to maintaining the parapatric
      boundary. However, Amblyomma limbatum in the pens had a shorter season of
      reproductive activity, and achieved much smaller numbers of reproductive females.
      This may inhibit successful colonization of cooler habitats to the south of its
      distribution.

PMID- 7628260
TI  - Anismus as a marker of sexual abuse. Consequences of abuse on anorectal motility.
AB  - Anorectal manometry was performed in 40 women, who consulted for functional
      disorders of the lower gastrointestinal tract and had been sexually abused.
      Anismus, defined as a rise in anal pressure during straining, was observed in 39
      of 40 abused women, but in only six of 20 healthy control women (P < 0.0001).
      Other parameters of anorectal manometry were compared with those observed in
      another control group composed of 31 nonabused women but with anismus, as well as
      the group of healthy controls. A decreased amplitude of anal voluntary
      contraction and an increased threshold volume in perception of rectal distension
      were observed in both abused and nonabused patients. A decreased amplitude of
      rectoanal inhibitory reflex, little rise in rectal pressure upon straining,
      frequent absence of initial contraction during rectal distension, and increased
      resting pressure at the lower part of the anal canal were observed in abused but
      not in nonabused patients, suggesting that these abnormalities, in association
      with anismus, suggest a pattern of motor activity in the anal canal that could be
      indicative of sexual abuse.

PMID- 7628261
TI  - Opioid and nonopioid analgesic drug effects on colon contractions in monkeys.
AB  - Opioid drugs administered postoperatively for pain relief cause increased
      frequency of nonpropulsive phasic contractions but decreased to absent propulsive
      migrating contractions in the colon, thus importantly influencing the duration of
      postoperative ileus. Ketorolac is thought to permit earlier return of bowel
      function postoperatively compared to morphine. Four monkeys had sets of three
      strain gauge force transducers implanted on the right and left colon at
      laparotomy. After recovery, animals were fasted overnight and had colon
      contractions recorded. After a 1-hr baseline period, 200 micrograms/kg morphine
      sulfate or 1 mg/kg ketorolac tromethamine was injected intramuscularly and
      recording continued. Each animal received four injections of each drug. Records
      were analyzed visually for frequency of phasic on migrating contractions. There
      was no difference in the frequency of phasic or migrating contractions after
      injection of ketorolac. Morphine, as expected, increased the frequency of phasic
      and decreased the frequency of migrating contractions in the colon. Ketorolac
      does not affect the frequency of colon contractions.

PMID- 7628262
TI  - Dermatoglyphic patterns in children with chronic constipation.
AB  - Analysis of the fine ridge configurations on the digits of the palms and soles
      (dermatoglyphics) may sometimes help in the diagnoses of certain medical
      disorders. Dermatoglyphic patterns have been reported to be associated with
      congenital anomalies, such as congenital heart disease, duodenal ulcer, abdominal
      pain, and constipation. The palmar dermatoglyphic patterns of 77 children with
      constipation (39 functional and 38 organic constipation) were recorded. The
      control group consisted of 84 children with inguinal hernia. Those patients with
      at least one arch identified on any digit of either hand were termed arch
      positive. There was no significant correlation between arch positivity and
      constipation (functional or organic), or inguinal hernia (chi square, P =
      0.9211). Therefore, the presence of palmar arches cannot be used as a screening
      device for children with chronic constipation, especially of organic etiology.

PMID- 7628263
TI  - Simultaneous two-level esophageal 24-hour pH monitoring in patients with mild and
      severe esophagitis. Does probe position influence results of esophageal
      monitoring?
AB  - Simultaneous ambulatory esophageal pH monitoring was performed in 10 patients
      (group 1) with normal distal acid exposure and in 40 patients (group 2) with
      pathological distal reflux. The probes were placed 5 and 10 cm above the lower
      esophageal sphincter to quantify variations of pH values that can be due to a
      displacement of pH sensor. In group 1 the median percent time with pH < 4 for
      total and upright monitoring periods and composite score were significantly lower
      at the proximal than the distal level. In group 2 all pH data were significantly
      lower at the proximal than the distal level. The patients with pathological
      reflux were subdivided into two subgroups based on endoscopic findings (mild and
      severe esophagitis). The patients with severe esophagitis showed a proximal acid
      reduction higher than in patients with mild esophagitis. Nine patients with mild
      esophagitis showed normal values at 10 cm, but all patients with severe
      esophagitis had abnormal proximal acid exposure.

PMID- 7628264
TI  - Gastric emptying and myoelectrical activity in children with nonulcer dyspepsia.
      Effect of cisapride.
AB  - We examined the effect of oral cisapride on gastric emptying time and
      myoelectrical activity using real-time ultrasonography and cutaneous
      electrogastrography in 10 children with nonulcer dyspepsia. A clear dominant
      frequency close to 3 cpm was present both at baseline and after eight weeks of
      cisapride. After cisapride, nine children had an increase in the normal slow wave
      percentage and the mean percentage of normal slow wave was significantly
      different (71.90 +/- 5.19% vs 79.16 +/- 5.54%; P < 0.01). Moreover, an increased
      stability of the dominant frequency, determined by computing the coefficient of
      variation before and after cisapride, was found (28.12 +/- 1.72% vs 23.61 +/-
      3.47%; P < 0.01). At baseline the gastric emptying time, expressed as T1/2, was
      139.76 +/- 40.04 min and at eight weeks 119.76 +/- 30.04 min (P = 0.06). As
      regards the relationship between EGG and gastric emptying, the proportion of
      children with improved normal slow wave percentage was similar to that with
      improved T1/2 emptying (Z = 0.57, P = 0.57). Thus, gastric electrical activity
      seems to be an important factor in the pathophysiology of nonulcer dyspepsia in
      children.

PMID- 7628265
TI  - Chronic effects of misoprostol in combination with the NSAID, diclofenac, on
      gastrointestinal tract of pigs. Relation to diarrheagenic activity, leukocyte
      infiltration, and mucosal leukotrienes.
AB  - To determine the mode of protective effects of misoprostol against the chronic
      gastrointestinal ulceration from the NSAID, diclofenac, studies were undertaken
      in domestic pigs, a model of human gastrointestinal ulceration, to determine (1)
      the effects of repeated daily dosing for 10 days of diclofenac 5 mg/kg/day twice
      a day (as Voltaren tablets) on the gastrointestinal morphology, 59fe-red blood
      loss, mucosal myeloperoxidase (MPO) activity (as an indicator of leukocyte
      infiltration), and mucosal leukotrienes (LTS); and (2) the mucosal protective
      effects of 10-40 micrograms/kg/day misoprostol twice a day (as Cytotec tablets)
      given with diclofenac 5 mg/kg/day twice a day compared with diclofenac 5
      mg/kg/day alone and aspirin 150 mg/kg/twice a day (USP tablets) as a standard.
      These effects were compared with the dose range for potential diarrheagenic
      effects of misoprostol (determined by fecal analysis of NA+, K+, CL-, CA2+, H2O,
      and phenol red transit) given alone or with diclofenac to determine if this could
      be discriminated from antiulcer effects of misoprostol. Plasma and gastric
      mucosal concentrations of the drugs were determined to establish if misoprostol
      affects diclofenac absorption/elimination, and vice versa. The results showed
      that: (1) diclofenac produced gastric mucosal damage without any prior or
      concurrent bleeding from the gastrointestinal tract, although aspirin
      significantly increased blood loss; (2) misoprostol produced a dose-related
      reduction in diclofenac-induced mucosal damage of the upper gastrointestinal
      tract; (3) no significant increase in mucosal MPO occurred with diclofenac
      despite mucosal damage being evident, (4) mucosal LTS were unaffected by the drug
      treatments; (5) plasma, gastric and intestinal concentrations of diclofenac were
      not affected by misoprostol, while conversely plasma misoprostol concentrations
      were not influenced by the diclofenac treatment; (6) no significant effects on
      fecal water, electrolyte, or phenol red transit times were observed with an of
      the drug-treatments; and (7) mild diarrhea observed as "loose bowel motions" was
      only observed in most pigs receiving the misoprostol treatments during fasting on
      days 9-10. Thus, misoprostol protects against chronic lesions/ulcers in the upper
      gastrointestinal tract from diclofenac without: (1) signs of diarrhea becoming
      evident (the latter occurring when there is reduced food intake), (2) generalized
      leukocyte infiltration or effects on mucosal LTs, or (3) any reduction in
      bioavailability of diclofenac.

PMID- 7628267
TI  - Effect of basic fibroblast growth factor on reinnervation of gastric
      microvessels. Possible relevance to ulcer recurrence.
AB  - Basic fibroblast growth factor (bFGF) has well-established angiogenic and ulcer
      healing actions. bFGF has also been found to induce neural regeneration in the
      central nervous system. Thus, the present study was undertaken to clarify the
      effect of basic fibroblast growth factor on the regeneration of autonomic nerves
      in the granulation tissues following the induction of experimental gastric ulcer
      induced by acetic acid in rats. Rats were divided into control, acetic acid
      alone, and acetic acid plus acid-stable human recombinant basic fibroblast growth
      factor (CS23, 1 microgram/100 g body wt., every 12 hr for three days, or one or
      two weeks, through oral gastric intubation) groups. As a result, few autonomic
      nerves were recognized surrounding the newly formed arterioles and venules in the
      acetic acid alone group. In the CS23-treated group, the cholinergic, calcitonin
      gene-related peptide and vasoactive intestinal peptide-immunoreactive nerves were
      clearly recognized near the microvessels, but few adrenergic nerves were seen
      even after CS23 treatment. From these observations, basic fibroblast growth
      factor was suggested to promote the reinnervation of the newly formed
      microvessels.

PMID- 7628266
TI  - Electrogastrography in healthy subjects. Evaluation of normal values, influence
      of age and gender.
AB  - Electrogastrography (EGG) permits measurements of the gastric electrical
      activity. However, normal values of electrical activity are poorly defined. In
      addition, limited data are available on the effect of age and gender. Therefore,
      in 40 healthy subjects (age range: 19-90 years) normal values for several EGG
      parameters were assessed after an overnight fast for 1 hr in the fasting and fed
      state after ingestion of a standardized solid-liquid meal. The electrical signals
      were captured by a pair of surface electrodes sonographically placed on the skin
      overlying the gastric antrum. The dominant electrical frequency was predominantly
      in the defined normal frequency range between 2 and 4 cycles per minute (cpm) (P
      < 0.001) and was higher in the postprandial than in the preprandial period (3.1
      cpm vs 2.8 cpm, P = 0.02). The instability of the electrical rhythm calculated by
      a dominant frequency instability coefficient (DFIC) was postprandially lower than
      in the fasting state (P = 0.04). The electrical power (amplitude) increased
      postprandially (postprandial to fasting power ratio = 2.4). To evaluate the
      influence of age and gender on normal values the subjects were divided into four
      groups (median age: male, 28 and 69 years; female, 25 and 67 years). The most
      parameters did not differ significantly between the groups. However, DFIC was
      different between the groups (P < 0.05), with elderly women revealing lowest
      DFIC. In conclusion, normal values for several EGG parameters evaluated in this
      study should be included in the analysis of gastric electrical activity. The
      magnitude of electrical frequency and power are not influenced by age and gender,
      whereas the instability of the electrical frequency is influenced by these
      factors.

PMID- 7628268
TI  - Diagnostic considerations in evaluation of patients presenting with melena and
      nondiagnostic esophagogastroduodenoscopy.
AB  - Proper evaluation of patients with melena and nondiagnostic
      esophagogastroduodenoscopy is comparatively undefined. We sought to determine the
      percentage of patients with melena and nondiagnostic upper endoscopy and assess
      the yield of further evaluation. Of 209 patients presenting with melena, 180
      underwent esophagogastroduodenoscopy as the initial study, which was
      nondiagnostic in 43 cases (24%). Further evaluation was pursued in 30. A presumed
      source of melena was found in 11 patients (37%), identified by colonoscopy in
      seven, bleeding scan in three, and barium enema plus flexible sigmoidoscopy in
      one. Nearly all such defined cases originated from the right colon. Small bowel
      contrast studies, flexible sigmoidoscopy of barium enema alone, and angiography
      failed to reveal a source. Our findings suggest that many (24%) patients
      presenting with melena will have nondiagnostic upper endoscopy; further
      evaluation reveals a potential source in 37% of this group, with the right colon
      being the most likely location of pathology; and colonoscopy is the test of
      choice in this cohort.

PMID- 7628269
TI  - Gastrospirillum hominis in asymptomatic healthy individuals.

PMID- 7628270
TI  - Consensus statement: octreotide dose titration in secretory diarrhea. Diarrhea
      Management Consensus Development Panel.
AB  - Octreotide is an effective therapeutic option in controlling secretory diarrhea
      of varied etiology. However, marked patient-to-patient differences in the
      antidiarrheal effects necessitate titration of octreotide dose in individual
      patients to achieve optimal symptom control. A consensus development panel
      established guidelines for octreotide dose titration in patients with secretory
      diarrhea. Overall, the panel recommended an aggressive approach in selecting the
      initial octreotide dose and in making subsequent dose escalations in patients
      with secretory diarrhea due to gastrointestinal tumors (eg, carcinoids, VIPomas),
      AIDS, dumping syndrome, short bowel syndrome, radiotherapy, or chemotherapy. To
      avoid hypoglycemia in patients with diabetes mellitus-associated secretory
      diarrhea, the panel recommended a low initial octreotide dose and a conservative
      titration regimen with close monitoring a blood glucose levels. The end point of
      therapy should focus on a reduction in diarrhea (frequency of bowel movements or
      stool volume) rather than normalization of hormonal profile. Overall, octreotide
      is well tolerated; principal side effects are transient injection site pain and
      gastrointestinal discomfort. For many patients with secretory diarrhea,
      octreotide therapy is expected to improve the overall health and quality of life
      and in the long run will lessen health care costs.

PMID- 7628272
TI  - Transferrin is not involved in initial uptake process of iron in rat duodenal
      mucosa. Ultrastructural study by x-ray energy spectrometry.
AB  - The role of transferrin in iron absorption by the duodenal mucosa in rats with
      iron deficiency and controls was evaluated immunohistochemically. Ferric iron was
      administered to each rat using a metallic gastric tube. Transferrin was stained
      by an immunoperoxidase method and iron with Prussian blue in the same duodenal
      sections and observed by light microscopy. The localization of transferrin
      differed from that of ferric iron both in rats with iron deficiency and in
      controls. In iron-deficient rats, transferrin was weakly stained after iron
      administration but was strongly stained after saline administration. In contrast,
      in controls, transferrin was weakly stained after saline administration but was
      strongly stained after iron administration. By electron microscopy, x-ray energy
      spectrometric analysis of the transferrin-positive areas showed no iron peak. In
      iron-deficient rats, accumulation of electron-dense transferrin-negative
      microgranules was observed in some of the duodenal columnar epithelium. X-ray
      energy spectrometric analysis of this area revealed iron, indicating iron
      absorption. These results suggest that mucosal transferrin does not act as a
      shuttle protein in iron absorption via the rat duodenal columnar epithelium, and
      the function of this protein may be to inform the absorptive cells of the iron
      status of the body as observed in other organs.

PMID- 7628273
TI  - Regional variation in canine intestinal muscle mass and function.
AB  - Our aim was to investigate the contribution of variations in intestinal muscle
      morphology or function to regional differences in motor properties in vivo. We
      quantitated intestinal muscle thickness and surface area along the canine gut and
      compared the in vitro contractile properties of the jejunum and ileum. The
      thickness and cross-sectional surface area of both circular and longitudinal
      muscle demonstrated a parabolic distribution along the intestine, with the
      greatest values occurring in the proximal and distal regions. The terminal ileum
      had the greatest circular (885 +/- 194 microns) and longitudinal muscle (367 +/-
      135 microns) thickness. Circular muscle was 2.5-3 times thicker than longitudinal
      muscle at all points. Passive tension was similar in muscle strips from the mid
      jejunum, mid-ileum, and terminal ileum (2.8 +/- 0.8, 2.5 +/- 0.4, and 2.3 +/- 0.8
      vs 2.5 +/- 0.5, 1.9 +/- 0.5, and 2.8 +/- 1.0, longitudinal and circular,
      respectively). Active and total tension, however, were significantly greater in
      longitudinal than circular muscle in mid-jejunum (active; 8.5 +/- 1.4 vs 5.6 +/-
      1.2, P < 0.05 and total 11.3 +/- 1.7 vs 8.1 +/- 1.2) and in mid-ileum (active 9.5
      +/- 1.6 vs 5.8 +/- 1.2 and total 12.0 +/- 1.6 vs 7.7 +/- 1.2). Values for each
      layer were similar in both sites. In contrast, in the terminal ileum,
      longitudinal and circular muscle strips demonstrated similar active (10.1 +/- 1.7
      vs 9.0 +/- 2.7, NS) and total tension (12.4 +/- 2.0 vs 11.9 +/- 3.4, NS). Dose
      response curves to carbachol (10(-8)-10(-2) M) were similar in all these regions.
      We conclude (1) there are regional variations in muscle mass but contractile
      properties are similar in jejunum and ileum; and (2) the unique motor properties
      of the terminal ileum may be related more to differences in muscle morphology and
      neural input than intrinsic function.

PMID- 7628271
TI  - Fecal bile acids, short-chain fatty acids, and bacteria after ileal pouch-anal
      anastomosis do not differ in patients with pouchitis.
AB  - Construction of an ileal reservoir changes the fecal bacterial flora and the
      fecal composition of bile acids and short-chain fatty acids. We examined the
      relationships between pouch inflammation (pouchitis) and pouch content, as
      assessed by analysis of fecal bacteria, bile acids, and short chain fatty acids.
      Four groups were studied: ileal pouch-anal anastomosis (IPAA) for ulcerative
      colitis with pouchitis (N = 10), IPAA without pouchitis (N =5), IPAA for familial
      adenomatous polyposis without pouchitis (N = 5); and Brooke ileostomy for
      ulcerative colitis, which served as controls (N = 5). Pouchitis was defined as >
      or = 7 points on an 18-point pouchitis disease activity index. Aerobic and
      anaerobic bacteria were quantitatively cultured. Total aqueous-phase bile acids
      were measured by thin-layer chromatography and an enzymatic 3 alpha-OH
      hydroxysteroid dehydrogenase method. Fecal short chain fatty acids were measured
      by gas liquid chromatography. All patients with an IPAA had higher ratios of
      anaerobes/aerobes and concentrations of anaerobic gram-negative rods than did
      patients with an ileostomy. There were no other differences between patient
      groups with respect to bacteria, aqueous-phase total bile acids, or fecal short
      chain fatty acids. Fecal concentrations of bacteria, bile acids, and short-chain
      fatty acids were similar in patients with and without pouchitis, indicating that
      these factors can not be the sole cause of pouchitis.

PMID- 7628274
TI  - Lactose maldigestion and recurrent abdominal pain in children.
AB  - Our objectives were to evaluate children with recurrent abdominal pain for
      lactose maldigestion and to assess factors which might predict lactose absorption
      status. One hundred thirty-seven children were referred for specialty evaluation
      of recurrent abdominal pain of at least three months' duration. Study subjects
      were evaluated by history and physical examination, dietary interviews,
      hematologic and biochemical laboratory testing, stool parasite examination, and
      radiologic or endoscopic structural examinations, as indicated. Lactose hydrogen
      breath testing was performed after challenge with 1 g/kg lactose 10% aqueous
      solution). There were 53 males and 84 females, whose ages ranged from 6 to 18
      years (9.64 +/- 2.9; mean +/- SD) Lactose maldigestion was detected in 33/137
      patients (24%). The prevalence of abdominal pain, bloating, gas, flatulence,
      diarrhea, and constipation was similar in children with or without lactose
      maldigestion. The perception of symptoms related to the ingestion of dairy
      products was similar in both groups. No other clinical parameter predicted
      lactose maldigestion. However, children with lactose maldigestion had overall
      clinical improvement with a lactose-restricted diet. Clinical evaluation alone
      cannot adequately predict the presence of lactose maldigestion in children.
      Formal evaluation for lactose maldigestion using breath hydrogen testing methods
      should be considered in children with recurrent abdominal pain.

PMID- 7628275
TI  - Daily gastrointestinal symptoms in women with and without a diagnosis of IBS.
AB  - This study compared daily gastrointestinal symptoms and stool characteristics
      across two menstrual cycles, and recalled bowel symptoms and psychological
      distress in women with irritable bowel syndrome (IBS, N = 22), IBS nonpatients
      (IBS-NP, N = 22), and controls (N = 25). Daily reports of abdominal pain,
      bloating, intestinal gas, constipation, and diarrhea did not differ significantly
      between the IBS and IBS-NP groups but both groups reported significantly higher
      symptoms than the control group. Stool consistencies was significantly looser in
      the IBS group relative to the control group. Menstrual cycle effects on symptoms
      were noted in all the groups. There were no significant differences in
      psychological distress between women with IBS and IBS-NP, but both groups
      reported significantly higher global distress than the control group. The lack of
      difference between the IBS and IBS-NP groups in contrast to the results of
      others, can be understood in terms of differences in recruitment strategies.

PMID- 7628276
TI  - Rectal bleeding in patients less than 50 years of age.
AB  - The study group consisted of 102 patients that presented for evaluation of rectal
      bleeding. All patients were 50 years of age or less and were evaluated with a
      flexible endoscope and an anoscope. The findings from each examination were
      recorded independently. Sigmoidoscopy and anoscopy were performed in 56 patients
      less than age 40 (group I), and colonoscopy and anoscopy were performed on 46
      patients between the ages of 40 but less than 50 years (group II). Anoscopy was
      superior to flexible endoscopy in detecting hemorrhoids in group I (P < 0.001 and
      group II (P < 0.004). The guaiac status of patients was not influenced by the
      presence of hemorrhoids. Three patients in group I and eight patients in group II
      had polyps. The likelihood of finding a polyp was not influenced by the guaiac
      status of the patients. Three patients in group I and one patient in group II had
      anal fissures that were missed with flexible endoscopy and detected with
      anoscopy. Five of 102 patients were noted to have diverticula; all of these were
      in group II. However, this was not felt to be the source of the bleed given the
      clinical history. Overall, six patients had colitis; all but one of these
      patients were less than 40 years of age. Flexible endoscopy and anoscopy provide
      complimentary information in middle-aged adults with rectal bleeding.

PMID- 7628277
TI  - Antiphospholipid antibodies in inflammatory bowel disease.

PMID- 7628278
TI  - Omeprazole inhibits growth of cancer cell line of colonic origin.
AB  - The direct effects of omeprazole on colonic cells has not been evaluated.
      Controversy exists regarding the potential adverse effects of omeprazole on cell
      proliferation. In order to mimic the in vivo situation in the patient treated
      with omeprazole, proliferation cell culture experiments were performed,
      monitoring directly the effects of gastrin and omeprazole both alone and in
      combination. Three colonic cancer cell lines were used, two with neuroendocrine
      features (NCI-H716, LCC-18) and one (DLD-1) not known to have these features. In
      these in vitro proliferation experiments, only the NCI-H716 colorectal cancer
      cell line responded to omeprazole by decreased proliferation (P < 0.05). The
      effect was concentration dependent shown for all doses of omeprazole used.
      Gastrin had a statistically significant effect on increasing proliferation in the
      NCS-H716 cell line alone but only at the highest concentration (10(-6) M).
      Omeprazole has a cytostatic effect on one of three colorectal cancer cell lines
      but the mechanism for this effect of omeprazole and its potential role in
      treatment awaits elucidation.

PMID- 7628279
TI  - Urinary organ specific neoantigen. A potentially diagnostic test for colorectal
      cancer.
AB  - Urinary organ-specific neoantigen from colorectal cancer patients has been used
      to make a monoclonal antibody, BAC 18.1. In this study we assessed the potential
      of this antibody for the diagnosis of colorectal cancer. We evaluated binding in
      both urine and effluent samples and compared it with effluent carcinoembryonic
      antigen standardized for both volume (nanograms per milliliter) and protein.
      Urinary organ-specific antigen as detected by BAC 18.1 was significantly greater
      in 29 cancer patients (A405: 0.717 +/- 0.500) vs 27 controls [0.121 +/- 0.273 (P
      < 0.05)]. Considerable overlap of binding of BAC 18.1 was observed in the colonic
      effluent of patients with CRC (N = 13), adenomas (N = 26), inflammatory bowel
      disease (N = 8), or having a normal colonoscopic examination (N = 24). CEA levels
      (nanograms per milliliter) were significantly elevated in the effluent samples of
      patients with a past history of colorectal cancer, as compared to that of normal
      individuals (P < 0.05). The presence of the M(r) 30,000 organ-specific neoantigen
      in colonic effluent was also demonstrated by western blot. Organ-specific
      neoantigen originates in the colon and is excreted into the urine, so the BAC
      18.1 binding levels in the urine may be a diagnostic aid for CRC.

PMID- 7628280
TI  - Natural killer cell activity in patients with pernicious anemia.
AB  - Patients with pernicious anemia have an estimated risk of gastric adenocarcinoma
      that ranges from three- to fivefold greater than that of the general population.
      It has been reported that NK cells may be involved in immunosurveillance against
      tumor spread. The natural killer cell activity of peripheral blood mononuclear
      cells was analyzed in 22 patients with pernicious anemia and in 19 healthy
      controls. Levels of natural killer cell activity against K-562 target cells were
      similar in control subjects and patients, regardless of gastrin levels and time
      elapsed since diagnosis. According to quantitative flow cytometry analysis,
      similar percentages of phenotypically defined NK cells (CD16+) were found in
      peripheral blood mononuclear cells from patients and healthy controls. Our
      results show that in pernicious anemia patients, the percentage of NK cells
      present in peripheral blood mononuclear cells and their lytic activity are
      normal.

PMID- 7628281
TI  - Molecular genetics of major histocompatibility complex class II genes in
      hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is the most common malignant tumor of the liver
      with a possible genetic predisposition. We have studied the HLA-DQ and -DR
      regions of 57 unrelated HCC patients of southern Chinese origin using molecular
      DNA techniques and compared them with 104 normal controls. Seventy-six hepatitis
      B carriers (HBsAg) were also studied. Restriction fragment length polymorphism
      (RFLP) was used to genotype the MHC class II DR beta, DQ alpha and DQ beta loci
      of the subjects. Polymerase chain reaction (PCR) using sequence primer for DQ
      beta genes was also performed. No significant difference was found in the HLA-DQ
      and -DR loci between HCC patients and normal controls, HCC patients and HBsAg
      carriers, or HBsAg carriers and normal controls respectively. Forty-one HCC
      patients were HBsAg positive, and no difference was found in the HLA-DQ and -DR
      genotype between this group of patients compared with the group of normal
      controls or HBsAg carriers. Thirty-six HCC patients had elevated alpha
      fetoprotein levels, and 15 HCC patients had normal levels. No difference in the
      HLA-DQ and -DR loci was detected between these two groups and the controls. The
      results suggest that HLA-DQ and -DR genotypes are not associated with
      hepatocellular carcinoma in southern Chinese.

PMID- 7628282
TI  - Pancreatic enlargement in obstructive jaundice. Effects of biliary stream
      diversion in humans.
AB  - To verify the influence of obstructive jaundice on pancreatic growth, the
      anteroposterior width of the pancreas was measured by computed tomography in 30
      cholangiocarcinoma patients excluded patients with distal bile duct tumor
      (jaundice group) and 74 control subjects. Follow-up examinations were performed
      on 12 patients with and without internal biliary drainage to elucidate the
      temporal relationship between pancreatic enlargement and the diversion of the
      obstructed biliary stream. Histologic analysis on autopsy samples from 13 control
      and 10 jaundice cases also was performed. Mean pancreatic head and body widths in
      the jaundice group were 2.93 +/- 0.3 cm and 2.01 +/- 0.3 cm, respectively. These
      values were significantly greater than those of the controls (2.13 +/- 0.3 cm and
      1.49 +/- 0.3 cm, P < 0.01). The glandular widths returned to their normal sizes
      following internal biliary drainage. No changes were seen in patients who
      underwent external drainage alone. Histologic examination revealed that
      enlargement of the acinar cells or of the islet of Langerhans was often seen in
      the jaundiced patients. Therefore obstructive jaundice is thought to cause
      pancreatic growth through a trophic effect by interrupting biliary circulation.

PMID- 7628283
TI  - Chronic pancreatitis caused by an autoimmune abnormality. Proposal of the concept
      of autoimmune pancreatitis.
AB  - Several authors have reported a case of chronic pancreatitis associated with
      Sjogren's syndrome in which an autoimmune mechanism may have been involved in the
      etiology and in which steroid therapy was effective. We recently encountered a
      patient with pancreatitis who had hyperglobulinemia, was autoantibody-positive,
      and responded to steroid therapy. This patient, however, failed to show any
      evidence of association with Sjogren's syndrome or other collagen diseases.
      Although the concept of autoimmune hepatitis and the criteria for diagnosing it
      have been established, autoimmune pancreatitis has not yet been defined as a
      clinical entity. We report a case of chronic pancreatitis in which an autoimmune
      mechanism is involved in the etiology and summarize the cases of pancreatitis
      suspected of being caused by an autoimmune mechanism in the Japanese and English
      literature.

PMID- 7628284
TI  - Role of omeprazole in prevention and treatment of postendoscopic variceal
      sclerotherapy esophageal complications. Double-blind randomized study.
AB  - Endoscopic variceal sclerotherapy-related esophageal complications are quite
      common. The potential efficacy of omeprazole in the prevention and treatment of
      postsclerotherapy esophageal complications was evaluated in 47 patients with
      portal hypertension in randomized, placebo-controlled study. Twenty-one patients
      in the omeprazole group and 23 patients in the placebo group completed the study.
      The two treatment groups were similar in regards to the etiology of portal
      hypertension, Child's class, and clinical characteristics. Esophageal ulcers
      developed in 16 patients in the omeprazole group (2.43 ulcers/patient) and 18
      patients in the placebo group (2.39 ulcers/patient). Most of the ulcers (> 90%)
      healed within 14 days in each group. Esophageal strictures requiring dilatation
      developed in two and one patient in the omeprazole and placebo groups,
      respectively. There was no statistically significant difference in regards to the
      complication rate between the two groups. We conclude that omeprazole is not
      effective for the prevention or treatment of postsclerotherapy esophageal
      complications.

PMID- 7628285
TI  - Course of thrombocytopenia of chronic liver disease after transjugular
      intrahepatic portosystemic shunts (TIPS). A retrospective analysis.
AB  - Thrombocytopenia associated with chronic liver disease presents a difficult
      management issue. Most reports conclude that portocaval and distal splenorenal
      shunts do not improve platelet counts in this setting. The response of
      thrombocytopenia after transjugular intrahepatic portosystemic shunt placement
      has not been studied. All platelet counts of 21 patients undergoing intrahepatic
      shunt placement were determined retrospectively to accumulate values at one month
      prior to procedure, weekly for the first month after the procedure, and monthly
      thereafter to six months. Comparison of pre- and postshunt platelet means showed
      a significant increase in counts in patients with a postshunt portal pressure
      gradient < 12 mm Hg, with the increment evident by one week after the procedure.
      This response was not seen when preshunt thrombocytopenia was used as the lone
      variable. This study suggests that the transjugular intrahepatic portosystemic
      shunt may improve the thrombocytopenia associated with liver cirrhosis when these
      pressure gradients are attained.

PMID- 7628286
TI  - Reliability of aminopyrine breath test using a single breath collection.

PMID- 7628287
TI  - Diagnostic yield of abscess drainage.

PMID- 7628288
TI  - Suppression of hepatitis C virus (HCV) replication by hepatitis D virus (HDV) in
      HIV-infected hemophiliacs with chronic hepatitis B and C.
AB  - Most hemophiliacs who are coinfected with human immunodeficiency virus (HIV) and
      hepatitis C virus (HCV) have high serum levels of HCV RNA. To study the impact of
      multiple hepatitis virus infections, we evaluated all eight chronic carriers of
      hepatitis B surface antigen (HBsAg) from a previously studied cohort of 99
      hemophiliacs with chronic HIV and HCV infections. Stored serum or plasma samples
      were tested for antibody to hepatitis D virus (anti-HDV) by ELISA; qualitatively
      for HCV RNA, HBV DNA, and HDV RNA by the polymerase chain reaction (PCR); and
      quantitively for HIV RNA, HCV RNA, and hepatitis B virus (HBV) DNA by a
      quantitative branched DNA signal amplification assay. HCV RNA was detected in
      only one of five patients with HDV infections on a cross-sectional study, and
      this individual had low levels (< 3.5 x 10(5) genome eq/ml) of HCV RNA. In
      contrast, all three without HDV infections had high levels (> 1.5 x 10(7) genome
      eq/ml) of HCV RNA. HIV RNA was present in all eight patients. There was no
      correlation between the level of HIV RNA and the presence of hepatitis viruses.
      Three of the eight patients (38%) died of liver failure and another has
      hypersplenism with hypoprothrombinemia. We conclude that HDV infection appears to
      suppress HCV replication and that liver failure is common in adult HIV-infected
      hemophiliacs with chronic HCV and HBV infections. These findings have
      implications for the therapy of HCV-infected hemophiliacs who are HBsAg positive.

PMID- 7628289
TI  - Non-HLA-linked hemochromatosis in a Chinese woman.
AB  - A 55 year-old Chinese woman is described with severe iron overload similar in
      degree and distribution to that seen in hereditary hemochromatosis in the
      Caucasian population. Autopsy findings confirmed severe iron overload in the
      liver, pancreas, skin, heart, and endocrine organs. Hepatic iron concentration
      was 482 mumol/g with a hepatic iron index of 8.8. There was no history of
      thalassemia, transfusions, or alcohol abuse. Pedigree analysis revealed two HLA
      identical brothers that had no clinical or biochemical evidence of iron overload.
      This case is an unusual example of severe iron overload in a non-Caucasian
      kindred and may represent a non-HLA-linked form of iron overload.

PMID- 7628290
TI  - Effect of S-adenosyl-L-methionine on ethanol cholestasis and hepatotoxicity in
      isolated perfused rat liver.
AB  - We investigated whether S-adenosyl-L-methionine (SAMe) influences the inhibitory
      effect of ethanol on bile secretion and ethanol hepatotoxicity in the isolated
      perfused rat liver. SAMe (25 mg/kg intramuscularly three times a day) was
      administered for three days consecutively. Liver was then isolated and perfused
      with taurocholate to stabilize bile secretion and exposed to 1% ethanol for 70
      min. The effect of ethanol on bile flow, bile salt biliary secretion, oxygen
      liver consumption, AST and LDH release in the perfusate, and hepatic
      concentration of glutathione, malondialdehyde, and diene conjugates was compared
      between SAMe-treated livers (N = 11) and paired controls (N = 11). Control
      experiments without ethanol were also performed (N = 6). Exposure to 1% ethanol
      induced a significantly (P < 0.03) higher inhibition of bile flow (-35% vs 17%)
      and bile salt secretion (-28% vs 16%) in untreated compared with SAMe-treated
      livers. During 1% ethanol exposure, the release of LDH and AST in the perfusate
      was significantly lower (P < 0.02) in SAMe-treated livers. Oxygen liver
      consumption was markedly inhibited by 1% ethanol administration (P < 0.02 vs
      controls without ethanol), an effect almost totally prevented by SAMe treatment
      (P < 0.02 vs ethanol controls). The hepatic concentration of total glutathione
      was significantly (P < 0.02) decreased by 1% ethanol exposure, but this effect
      was less pronounced in SAMe-treated than in untreated controls (P < 0.02). The
      hepatic levels of malondialdehyde and diene conjugates were not significantly
      changed by ethanol exposure in either SAMe-treated or control livers in
      comparison to ethanol-free controls.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7628291
TI  - Chronobiology and chronotherapy in medicine.
AB  - There is a fascinating and exceedingly important area of medicine that most of us
      have not been exposed to at any level of our medical training. This relatively
      new area is termed chronobiology; that is, how time-related events shape our
      daily biologic responses and apply to any aspect of medicine with regard to
      altering pathophysiology and treatment response. For example, normally occurring
      circadian (daily cycles, approximately 24 hours) events, such as nadirs in
      epinephrine and cortisol levels that occur in the body around 10 PM to 4 AM and
      elevated histamine and other mediator levels that occur between midnight and 4
      AM, play a major role in the worsening of asthma during the night. In fact, this
      nocturnal exacerbation occurs in the majority of asthmatic patients. Because all
      biologic functions, including those of cells, organs, and the entire body, have
      circadian, ultradian (less than 22 hours), or infradian (greater than 26 hours)
      rhythms, understanding the pathophysiology and treatment of disease needs to be
      viewed with these changes in mind. Biologic rhythms are ingrained, and although
      they can be changed over time by changing the wake-sleep cycle, these alterations
      occur over days. However, sleep itself can adversely affect the pathophysiology
      of disease. The non-light/dark influence of biologic rhythms was first described
      in 1729 by the French astronomer Jean-Jacques de Mairan. Previously, it was
      presumed that the small red flowers of the plant Kalanchoe bloss feldiuna opened
      in the day because of the sunlight and closed at night because of the darkness.
      When de Mairan placed the plant in total darkness, the opening and closing of the
      flowers still occurred on its intrinsic circadian basis. It is intriguing to
      think about how the time of day governs the pathophysiology of disease. On
      awakening in the morning, heart rate and blood pressure briskly increase, as do
      platelet aggregability and other clotting factors. This can be linked to the
      acrophase (peak event) of heart attacks. During the afternoon we hit our best
      mental and physical performance, which explains why most of us state that "I am
      not a morning person." Even the tolerance for alcohol varies over the 24-hour
      cycle, with best tolerance around 5 pm (i.e. "Doctor, I only have a couple of
      highballs before dinner"). Thus, all biologic functions, from those of the cell,
      the tissue, the organs, and the entire body, run on a cycle of altering activity
      and function.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7628292
TI  - Expressed human UGT1.4 protein catalyzes the formation of quaternary ammonium
      linked glucuronides.
AB  - In humans, the metabolism of a number of tertiary amine-containing
      pharmacological agents to quaternary ammonium-linked glucuronides, catalyzed by
      UDP-glucuronosyltransferase (UGT), represents a unique and important metabolic
      pathway for these compounds. A full-length cDNA-encoding human UGT1.4 (the so
      called "minor" human bilirubin UGT) was inserted into the expression vector pREP9
      and transfected into human embryonic kidney 293 cells, and stable transfectants
      were obtained after geneticin selection. As expected, the expressed protein had
      low catalytic activity toward bilirubin. However, expressed human UGT1.4 protein
      exhibited glucuronidation activity toward tertiary amine substrates, such as
      imipramine, cyproheptadine, tripelennamine, and chlorpromazine, which form
      quaternary ammonium-linked glucuronides. Carcinogenic primary amines (beta
      naphthylamine, benzidine, and 4-aminobiphenyl) also reacted with the expressed
      UGT1.4 protein at rates approximately 10-fold higher than the rates for
      quaternary ammonium glucuronide formation. Although a number of other UGT gene
      products are capable of catalyzing the glucuronidation of primary amine
      substrates, expressed human UGT1.4 protein is the only UGT isoform that has been
      shown to conjugate tertiary amine substrates, forming quaternary ammonium-linked
      glucuronides.

PMID- 7628293
TI  - Sulfation and glucuronidation of acetaminophen by human hepatocytes cultured on
      Matrigel and type 1 collagen reproduces conjugation in vivo.
AB  - Our previous studies demonstrated marked sex differences in the metabolism of
      acetaminophen in rats both in vivo and in hepatocyte culture. This study examined
      the sex differences in human acetaminophen metabolism, and the ability to
      reproduce in vivo metabolism in human hepatocyte cultured on Matrigel vs. type 1
      collagen. Human hepatocytes were isolated by collagenase perfusion of 10-15 g
      biopsies of patients without liver disease undergoing elective abdominal
      operations (8 females, age 41.3 +/- 19.3 years; 6 males, age 47.7 +/- 21.3
      years). Postoperatively, patients were given 1 g of acetaminophen orally and a 24
      hr urine collected to determine the metabolic fate. There were no sex differences
      in acetaminophen conjugation in vivo, nor in the hepatic acetaminophen
      sulfotransferase activities as observed in the rodents. Hepatocytes were cultured
      with acetaminophen (0, 150, 250, 500, and 1000 microM) on Matrigel and type I
      collagen. Acetaminophen glucuronidation predominated over acetaminophen sulfation
      just as in vivo without sex differences on days 1 and 2 in culture. By days 3 and
      4, however, glucuronidation by female hepatocytes became enhanced compared with
      males. With increasing acetaminophen concentration (dose), there was a linear
      increase in sulfate and glucuronide conjugation without saturation of either
      pathway as observed in the rat. CONCLUSIONS: 1) there are no sex differences in
      acetaminophen metabolism or acetaminophen sulfotransferase activity as observed
      in the rat; 2) acetaminophen sulfation and glucuronidation by cultured human
      hepatocytes in vitro replicated in vivo metabolism on matrigel and type 1
      collagen for the first 2 days in culture; and 3) glucuronidation became enhanced
      with time in the culture of female, but not male hepatocytes.

PMID- 7628294
TI  - Comparative metabolism of 3'-azido-3'-deoxythymidine in cultured hepatocytes from
      rats, dogs, monkeys, and humans.
AB  - 3'-Azido-3'-deoxythymidine (AZT), the main antiretroviral drug used against Human
      Immunodeficiency Virus, was approved by the Food and Drug Administration in 1987
      with only little knowledge concerning its metabolism. The aim of our study was to
      evaluate the interspecies variability of AZT metabolism in primary cultures of
      hepatocytes, freshly isolated from rats, dogs, monkeys, and humans. Cultures were
      exposed to 10 or 100 microM [3H]AZT. Extracellular and intracellular compartments
      were analyzed using a HPLC method. Intracellular and extracellular metabolic
      patterns were qualitatively similar, but very low amounts of AZT and metabolites
      were detected within hepatocytes. In all species, the 3'-azido-3'-deoxy-5'-O-beta
      D-glucopyranuronosylthymidine (GAZT) was identified as the major metabolite of
      AZT. In addition to this glucuronide, two minor peaks were detected: one
      coeluting with 3'-amino-3'-deoxythymidine(AMT); and the other with a retention
      time corresponding, on the basis of the publications in this field, to 3'-amino
      3'-deoxythymidine glucuronide. However, further investigation allowed this
      compound to be characterized as tritiated water, possibly representing a
      catabolic endproduct of AZT. Although glucuronidation was the main metabolic
      pathway in the four species studied, AZT biotransformation rate was much lower in
      rat and dog hepatocytes than in monkey and human ones. Finally, an excellent
      correlation was obtained between in vivo and in vitro metabolic data.

PMID- 7628295
TI  - Effect of iron overload on the metabolism and urinary recovery of 3
      hydroxypyridin-4-one chelating agents in the rat.
AB  - Three orally active iron chelating agents from the 3-hydroxypyridin-4-one series
      of compounds were administered by gavage to both normal and iron-overloaded (500
      mg Fe/kg) rats at a dose of 450 mumol/kg to investigate the effect of iron
      loading on metabolism and urinary recovery. Compounds selected for investigation
      were either poorly metabolized [1-(2'-hydroxyethyl) derivative, CP102] or
      predominantly biotransformed by either phase I [1,2-diethyl derivative, CP94] or
      phase II (1,2-dimethyl derivative, CP20) metabolic pathways. Unchanged drug and
      metabolite(s) recovered in urine were determined by HPLC and iron levels by
      atomic absorption spectrometry. Significant differences in recovery of unchanged
      drug were seen for both CP20 (L1) and CP94 between normal and iron-overloaded
      animals. In contrast, no such difference was seen for the poorly metabolized
      compound, CP102. For CP20 (L1), the proportion of unchanged drug excreted in the
      urine increased from 36.2 +/- 9.9% in normal animals to 78.7 +/- 8.1% (p < or =
      0.02) in iron-loaded animals and 20.1 +/- 4.5% to 39.9 +/- 8.6% for CP94 (p < or
      = 0.05). A significant decrease in metabolite recovery of CP20 (L1) was seen with
      the 3-O-glucuronide conjugate decreasing from 38.2 +/- 8.8% in normal animals to
      2.5 +/- 2.0% in the iron-overloaded group. The decrease of the 2-(1'
      hydroxyethyl) metabolite of CP94 from 41.4 +/- 6.6% to 29.4 +/- 4.6% in the iron
      loaded animals was, however, not statistically significant. Total dose recovered
      in the urine between normal and iron-overloaded animals was only significant for
      CP94 (p < or = 0.05).

PMID- 7628296
TI  - Human liver cytochrome P4503A biotransformation of the cyclosporin derivative SDZ
      IMM 125.
AB  - In humans, cytochrome P4503A (CYP3A) is the major cytochrome P450 gene family
      that metabolizes SDZ IMM 125 (IMM) to its primary metabolites. Human liver
      microsomes could be used for this study, because the metabolite profile matched
      that found in human blood. The apparent affinity (KM) of IMM for the cytochrome
      P450 proteins (5.1 +/- 1.8 microM) is similar to that of cyclosporin A (CSA). CSA
      competitively inhibited the metabolism of IMM, increasing the KM 2- and 4.6-fold
      in the presence of 4 and 10 microM CSA, respectively (Ki 3.8 +/- 1.1 microM).
      Ketoconazole exhibited competitive inhibition kinetics toward IMM
      biotransformation, increasing the KM of IMM 1.8-fold at 0.5 microM ketoconazole
      and 3.5-fold at 1 microM ketoconazole, with no effect on Vmax (Ki of 0.5 +/- 0.4
      microM). These results indicate that both CSA and ketoconazole would cause drug
      interactions, interfering with the biotransformation of IMM. The metabolism of
      IMM was also greatly inhibited (approximately 80%) by the CYP3A suicide substrate
      triacetyloleandomycin and a CYP3A inhibitory antibody, indicating the involvement
      of CYP3A proteins in the biotransformation of IMM. Confirmation of CYP3A4
      involvement in the formation of the three primary IMM metabolites was
      demonstrated with recombinant cells expressing human CYP3A4. Therefore, compounds
      interacting with CYP3A proteins are expected to cause drug-drug interactions
      (i.e. the antimycotics ketoconazole and clotrimazole, the steroids
      ethinylestradiol and testosterone, the ergots, the calcium channel blocker
      nifedipine, and the immunosuppressants FK-506 and rapamycin).(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7628297
TI  - Sites of biotransformation for the cyclosporin derivative SDZ IMM 125 using human
      liver and kidney slices and intestine. Comparison with rat liver slices and
      cyclosporin A metabolism.
AB  - SDZ IMM 125 (IMM), the hydroxyethyl derivative of cyclosporin A (CSA), is
      metabolized by human liver slices to analogous primary metabolites, hydroxylated
      IMM1 and IMM9 and N-demethylated IMM4N, as for CSA (M17/AM1, M1/AM9, and
      M21/AM4N), but the rate and extent of IMM biotransformation is less than for CSA.
      Initial rates of IMM metabolite formation in the human liver slice cultures are
      6.6 +/- 2.8 nmol/hr/g liver at 1 microM IMM and 24.3 +/- 22.9 nmol/hr/g liver at
      10 microM IMM, whereas the rate of CSA metabolite formation is 1.8-fold faster at
      both concentrations. The percentage of unchanged IMM is 73% at 1 microM and 80%
      at 10 microM after 24 hr, reflecting the lower extent of IMM metabolism, about
      one-third (1 microM) and one-half (10 microM) that of CSA. In rat liver slices,
      IMM is metabolized to the same primary metabolites as in human liver slices, but
      more slowly and remains 90% unchanged at 24 hr. Human jejunum formed the same
      primary metabolites of IMM and CSA as in liver. Upscaling the slice rate of
      biotransformation revealed that human jejunum would contribute considerably to
      the first-pass of IMM and CSA, being approximately 2 to 3-fold slower than the
      rate in liver. The inhibition of both IMM and CSA biotransformation by
      triacetyloleandomycin implicates the involvement of cytochrome P4503A proteins.
      Human kidney cortex slices metabolized IMM to IMM1 and IMM9, accounting for
      approximately 75% of the total metabolites. Total metabolite formation
      represented approximately 64% of liver metabolite formation.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7628298
TI  - Comparative disposition of morphine-3-glucuronide during separate intravenous
      infusions of morphine and morphine-3-glucuronide in sheep. Importance of the
      kidney.
AB  - The disposition of morphine-3-glucuronide (M3G) in sheep was compared during
      separate constant infusions of morphine and M3G. Five ewes received a 15-min
      loading dose, followed by a constant infusion of morphine sulfate (10 mg/hr) or
      M3G (4 mg/hr for 4 sheep, 7.5 mg/hr for 1 sheep) for a further 5.75 hr. During
      the 5th-6th hr of infusion, blood was collected simultaneously from the aorta,
      pulmonary artery, hepatic vein, hepatic portal vein, renal vein, and posterior
      vena cava. Additional samples were collected from the aorta from 0 to 5 hr and
      from 6 to 48 hr. Urine was collected via an indwelling catheter from 0 to 6 hr,
      with further free-flowing urine up to 48 hr. An HPLC assay was used to determine
      simultaneously morphine, M3G, and morphine-6-glucuronide (M6G) in plasma and
      urine. Constant concentrations of morphine, M3G, and M6G in plasma were achieved
      during the 5- to 6-hr period of infusion with morphine, as were the
      concentrations of M3G while M3G was infused. Regional net extraction ratios and
      total and regional clearances were calculated during the 5- to 6-hr period. After
      the infusions were ceased, there was prolonged elimination of M3G formed in situ
      from morphine compared to when infused as M3G. No morphine or M6G was detected in
      the plasma during and after infusion with M3G, nor were they found in urine
      collected up to 6 hr.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7628299
TI  - Characterization of the in vitro glucuronidation of flurbiprofen enantiomers.
AB  - To investigate the glucuronidation of the R- and S-enantiomers of the
      nonsteroidal antiinflammatory drug, flurbiprofen, by liver microsomes of several
      mammals, including humans, a new and reliable HPLC method for the separation and
      quantification of the corresponding diastereoisomeric glucuronides has been
      developed. Interspecies comparison revealed that the glucuronidation of
      flurbiprofen was highly efficient with liver microsomes of humans, monkeys, rats,
      and guinea pigs (in decreasing ranking order). Gunn rats, which present a genetic
      defect in the bilirubin UDP-glucuronosyltransferase (UGT) isoforms, were still
      able to glucuronidate the drug. The R-enantiomer was glucuronidated faster than
      the S-form by liver microsomes of rats and humans. Although the KM of
      glucuronidation of R- and S-enantiomers by rat liver UGT were in same order of
      magnitude (apparent KM 0.52 and 0.57 mM, respectively), the apparent Vmax's were
      significantly different (9.34 and 5.48 nmol/min.mg of protein). Regardless of the
      enantiomer considered, the glucuronidation of flurbiprofen was strongly increased
      up to 5-fold by treatment of rats with phenobarbital and, at a lower extent, by 3
      methylcholanthrene. In contrast, the treatment of rats with ciprofibrate markedly
      decreased the activity. Glucuronidation of R-flurbiprofen was more enhanced by
      phenobarbital than that of the S-antipode. Each flurbiprofen enantiomer could
      weakly inhibit the glucuronidation of its antipode in a noncompetitive way. The
      apparent Ki was 0.51 mM with R-flurbiprofen as a substrate, and 0.37 mM with S
      enantiomer. On the other hand, the rat liver UGT2B1 isoform, stably expressed in
      V79 cells, could glucuronidate flurbiprofen in an appreciable amount.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7628300
TI  - In vivo disposition of caffeine predicted from hepatic microsomal and hepatocyte
      data.
AB  - The kinetics of caffeine metabolism has been investigated in freshly isolated
      hepatocytes, hepatic microsomes, and in vivo in male Sprague-Dawley rats. A
      simple Michaelis-Menten model provides an adequate description of each of the
      three sets of data. There is reasonable agreement between the KM values for the
      three systems (56-200 microM). Vmax values for hepatocytes and microsomes show
      good agreement when expressed in the same units using scaling factors for hepatic
      cellularity and microsomal protein yield [315 and 420 nmol/min/standard rat
      weight (SRW), respectively]. Both values slightly exceed the in vivo-determined
      Vmax (190 nmol/min/SRW). Taking the Vmax/KM ratio (intrinsic clearance) as the
      basis for scaling, the in vitro data from both the hepatocyte (2.6 ml/min/SRW)
      and microsomal (2.7 ml/min/SRW) studies provide a good prediction of the in vivo
      total body clearance (3.4 ml/min/SRW).

PMID- 7628301
TI  - Reduction of the prodrug loperamide oxide to its active drug loperamide in the
      gut of rats, dogs, and humans.
AB  - Loperamide oxide (LOPOX) is a prodrug of loperamide (LOP). The reduction of LOPOX
      to LOP was investigated to provide a pharmacokinetic basis for the
      pharmacodynamics and improved side effect profile of the prodrug. Reduction of
      LOPOX was studied in vitro in gut contents, gut flora, intestinal cells, and
      hepatocytes. In vivo pharmacokinetics and metabolism of LOPOX and LOP were
      compared in the dog. LOPOX could be efficiently reduced in the gut contents of
      rats, dogs, and humans, with the most extensive reduction found in cecal
      contents. Reduction was diminished to 13% of the anaerobic LOPOX reductase
      activity in the presence of oxygen and to 2.5% of the original activity by heat
      treatment of the contents. In human ileal effluents, LOPOX reductase activity was
      similar in oxygen and heat sensitivity. In the rat, the cecum contained on
      average 89.2% of the total activity in the contents of the upper part of the
      intestine. In the dog, there was a gradual increase in LOPOX reductase activity
      from the proximal small intestine toward the cecum. In germ-free rats, the cecum
      contained < 1% of the activity of the small intestine. Isolated intestinal
      microflora of rat and dog was able to reduce LOPOX to LOP under anaerobic
      conditions, indicating that the microflora was primarily involved in the
      reduction. In its absence (i.e. in germ-free rats), reduction could still be
      conducted by other unknown components of the gut contents. In isolated intestinal
      cells, the initial rate of drug uptake was approximately 3-10 times faster for
      LOP than for LOPOX.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7628302
TI  - Metabolism and elimination of 5,6-dimethylxanthenone-4-acetic acid in the
      isolated perfused rat liver.
AB  - 5,6-Dimethylxanthenone-4-acetic acid (DXAA) is a synthetic xanthenone derivative
      that is active against murine solid tumors and is being formulated for clinical
      trials. This study used the isolated perfused rat liver to compare the hepatic
      metabolism and biliary excretion of DXAA with flavone-8-acetic acid (FAA), a
      synthetic flavonoid undergoing clinical evaluation as an anticancer drug.
      Perfusate, bile, and liver samples were assayed for parent drug and metabolites
      by HPLC. Three FAA metabolites were present in bile, and one of these coeluted
      with FAA acyl glucuronide. Alkaline hydrolysis of high-dose DXAA bile samples
      resulted in the disappearance of 5 of 7 metabolite peaks. One biliary metabolite
      was identified by mass spectrometry as the acyl glucuronide and its presence in
      bile accounted for > 50% of the DXAA dose. A second compound that was resistant
      to alkaline hydrolysis was characterized as a hydroxylated DXAA metabolite. A
      total of 28% of the high dose DXAA was recovered unchanged in the perfusate,
      liver, and bile, compared with 11% of the low dose DXAA and 40% of the FAA dose.
      Protein binding of DXAA in perfusate was saturable, ranging from 94.5% at 112
      microM to 72.4% at 1125 microM, whereas binding in human plasma was > 99% at
      concentrations between 11.5 and 1243 microM. This study demonstrates that DXAA
      undergoes extensive acyl glucuronidation followed by biliary excretion in the
      isolated perfused rat liver. Its hepatic metabolism may be saturable, and DXAA
      seems to be more extensively metabolized than FAA. Finally, DXAA protein binding
      in human plasma is high and not dose-dependent at concentrations likely to be
      clinically relevant.

PMID- 7628303
TI  - Reactivity of tolmetin glucuronide with human serum albumin. Identification of
      binding sites and mechanisms of reaction by tandem mass spectrometry.
AB  - The structures of adducts formed from in vitro incubation of a drug (tolmetin)
      glucuronide (TG) and human serum albumin (HSA), and the preferred binding sites
      on this protein were determined by mass spectrometry. In addition, the
      concentration dependence of covalent modification of HSA by TG was studied at
      three different concentration ratios of TG to HSA. Protein adducts were
      enzymatically digested and peptide fragments were separated by HPLC. Tolmetin
      containing peptides (indicated by absorbance at 313 nm) were analyzed by liquid
      secondary-ion mass spectrometry, continuous flow-fast atom bombardment mass
      spectrometry, and collision-induced dissociation using a four-sector tandem mass
      spectrometer, matrix-assisted laser desorption ionization-time-of-flight-mass
      spectrometry, and in selected cases by Edman sequencing. The identified peptides
      contained tolmetin linked covalently via a glucuronic acid to a protein lysine
      group (lysine 199 and to a lesser extent lysines 195 and 525) or tolmetin
      directly linked to lysines (lysines 199 and 541), serines (serines 220, 232, and
      480), or arginines (arginine 222). In addition, there was indirect evidence for
      binding of TG to lysine 541, and binding of tolmetin to arginine 521. Our results
      establish that the binding of these reactive metabolites to nucleophilic sites of
      proteins occur via two different mechanisms: one involving imine (Schiff base)
      formation and the other involving nucleophilic displacement of glucuronic acid.
      Our data suggest, however, that the former, in which the glucuronic acid moiety
      of the acyl glucuronide is retained within the adducts, is favored at lower
      (closer to physiological) metabolite concentrations.

PMID- 7628304
TI  - Identification of tamoxifen metabolites in human Hep G2 cell line, human liver
      homogenate, and patients on long-term therapy for breast cancer.
AB  - The metabolism of tamoxifen was examined in human liver homogenate and human Hep
      G2 cell line preparations by LC/electro spray ionization/MS. Several metabolites
      were detected in the human liver homogenate extracts, namely N
      didesmethyltamoxifen (metabolite I), alpha-hydroxytamoxifen (metabolite II), 4
      hydroxytamoxifen (metabolite III), N-desmethyltamoxifen (metabolite IV), and
      tamoxifen N-oxide (metabolite V). Metabolites II, III, IV, and V were observed in
      the samples after incubating tamoxifen with the human Hep G2 cell line. When
      these results were compared with the metabolic profiles in patients, apart from
      metabolites I-V, alpha-hydroxy-N-desmethyltamoxifen (VI) and 4-hydroxy N
      desmethyltamoxifen (VII) were present in all the plasma samples. In addition, in
      patients who had received tamoxifen treatment daily for > 6 months, several minor
      metabolites were detected, namely 4-hydroxytamoxifen N-oxide (metabolite VIII)
      and two dihydroxylated analogs (metabolites IX and X). The precise positions of
      the hydroxylation have yet to be determined.

PMID- 7628305
TI  - In vitro metabolism of tirilazad mesylate in male and female rats. Contribution
      of cytochrome P4502C11 and delta 4-5 alpha-reductase.
AB  - Tirilazad mesylate, a potent inhibitor of membrane lipid peroxidation in vitro,
      is under clinical development for the treatment of subarachnoid hemorrhage and
      head injury. In rat, tirilazad seems to be highly extracted and is cleared almost
      exclusively via hepatic elimination. The biotransformation of tirilazad has been
      investigated in liver microsomal preparations from adult male and female Sprague
      Dawley rats. Tirilazad metabolism in male rat liver microsomes resulted in the
      formation of two primary metabolites: M1 and M2. In incubations with female rat
      liver microsomes, M2 was the only primary metabolite detected. Structural
      characterization of M1 and M2 by mass spectrometry demonstrated that M2 was
      formed by reduction of the delta 4-double bond in the steroid A-ring, whereas M1
      arose from oxidative desaturation of one pyrrolidine ring. Further structural
      analysis of M2 by proton NMR demonstrated that reduction at C-5 had occurred by
      addition of hydrogen in the alpha-configuration. Using metabolic probes and
      antibodies specific to individual hepatic microsomal enzymes, CYP2C11 and 3-oxo-5
      alpha-steroid:NADP+ delta 4-oxidoreductase (5 alpha-reductase) were identified as
      responsible for the formation of M1 and M2, respectively. The formation of M1 was
      inhibited by testosterone, nicotine, cimetidine, and anti-CYP2C11 IgG. The
      formation of M2 was inhibited by finasteride, a potent inhibitor of 5 alpha
      reductase. Kinetic analysis of CYP2C11-mediated M1 formation in male rat liver
      microsomal incubations revealed that M1 formation occurred through a low
      affinity/low-capacity process (KM = 16.67 microM, Vmax = 0.978 nmol/mg microsomal
      protein/min); the formation of M2 was mediated by 5 alpha-reductase in a high
      affinity/low-capacity process (KM = 3.07 microM, Vmax = 1.06 nmol/mg microsomal
      protein/min). In contrast, the formation of M2 in female rat liver microsomes was
      mediated by 5 alpha-reductase in a high-affinity/high-capacity process (KM = 2.72
      microM, Vmax = 4.11 nmol/mg microsomal protein/min). Comparison of calculated
      intrinsic formation clearances (Vmax/KM) for M1 and M2 indicated that the female
      rat possessed a greater in vitro metabolic capacity for tirilazad
      biotransformation than the male rat. Therefore, the clearance of tirilazad
      mesylate in the rat is mediated primarily by rat liver 5 alpha-reductase, and the
      capacity in the female rat is 5-fold the capacity in the male. These observations
      correlate with documented differences in 5 alpha-reductase activity and predict a
      gender difference in tirilazad hepatic clearance in vivo.

PMID- 7628306
TI  - Kinetics of drug metabolism in rat liver slices. Rates of oxidation of
      ethoxycoumarin and tolbutamide, examples of high- and low-clearance compounds.
AB  - Ethoxycoumarin (EC) and tolbutamide (TOL) were selected as examples of high- and
      low-clearance drugs, respectively, to investigate suitable methodologies for
      obtaining kinetic data on metabolism by precision-cut rat liver slices. A number
      of characteristics of the slice incubation were compound-dependent. TOL showed
      linear rates of metabolism over a longer time period than EC and was insensitive
      to the method of incubation (rotating vials and gyrating culture plates). Also,
      the need for complete tissue disruption (e.g. via sonication) before analysis was
      essential for EC but unimportant for TOL. This may suggest that conjugates do not
      freely diffuse out of the liver slice unlike oxidative metabolites. Both drugs
      showed rates of metabolism that were dependent on slice thickness (150-530
      microns). A high turnover (intrinsic clearance 7.9 microliters/min) and low KM
      (1.3 microM) for EC, and a low turnover (intrinsic clearance 0.8 microliter/min)
      and high KM (707 microM) for TOL were determined in slices. These differences in
      kinetic behavior are comparable with those seen in hepatic microsomes, freshly
      isolated hepatocytes, and in vivo.

PMID- 7628307
TI  - Thiopurine methyltransferase pharmacogenetics. Cloning of human liver cDNA and a
      processed pseudogene on human chromosome 18q21.1.
AB  - Thiopurine methyltransferase (TPMT) is a genetically polymorphic enzyme that
      catalyzes the S-methylation of thiopurine drugs such as 6-mercaptopurine. This
      genetic polymorphism is an important factor responsible for individual variation
      in thiopurine drug response. A cDNA for TPMT has been cloned from T84 human colon
      carcinoma cells. Northern blot analysis of multiple human tissues was performed
      with the T84 human colon carcinoma TPMT cDNA open reading frame (ORF) as a probe
      as one step toward understanding the molecular basis for the TPMT genetic
      polymorphism. Three mRNA species (approximately 1.4, 2.0, and 3.6 kb in length)
      were present in all tissues studied, including liver. However, none of these
      mRNAs matched the length of the 2.7 kb T84 TPMT cDNA. Therefore, it was important
      to clone a TPMT cDNA from a human drug-metabolizing organ such as the liver to
      determine whether its sequence matched that of the cDNA cloned from the T84 cell
      line. A human liver cDNA library was screened with the T84 TPMT cDNA ORF as a
      probe, and a 1.8 kb cDNA was isolated with a coding region sequence identical to
      that of the T84 TPMT cDNA. The TPMT cDNA ORF was then used to screen a human
      lymphocytes genomic DNA library in an attempt to clone the TPMT gene(s) in
      humans. Three intronless clones were isolated with identical ORF sequences that
      were 96% identical to that of the TPMT cDNA, but which contained multiple
      nucleotide substitutions and one deletion. The 3'- and 5'-flanking regions of one
      of the genomic DNA clones were sequenced.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7628308
TI  - N4-hydroxylation of sulfamethoxazole by cytochrome P450 of the cytochrome P4502C
      subfamily and reduction of sulfamethoxazole hydroxylamine in human and rat
      hepatic microsomes.
AB  - The N4-hydroxylation of sulfamethoxazole (SMX) to its hydroxylamine (SMX-HA)
      metabolite is the first step in the formation of reactive metabolites responsible
      for mediating hypersensitivity reactions associated with this compound. In rat
      hepatic microsomes, the NADPH-dependent oxidation of SMX to SMX-HA was increased
      3-fold by pretreatment of rats with phenobarbital. Other cytochrome P450 (CYP)
      inducers were ineffective. The constitutive and induced SMX N-hydroxylation
      activities were inhibited by tolbutamide, and induction of SMX-HA activity
      paralleled the induction of progesterone 21-hydroxylase activity, a marker for
      CYP2C6. SMX N-hydroxylation in phenobarbital-treated rat hepatic microsomes was
      inhibited 70% by anti-CYP2C6 antisera. Thus, the N4-hydroxylation of SMX by rat
      hepatic microsomes was mediated by members of the CYP2C subfamily, probably
      CYP2C6. In a panel of human microsomes, SMX-HA formation correlated with
      tolbutamide hydroxylase activity (r = 0.75; p = 0.01); CYP2C9 content (r = 0.79;
      p < 0.01) and was inhibited 70% by 500 microM tolbutamide and 90% by 100 microM
      sulfaphenazole. Recombinant CYP2C9 catalyzed the N-hydroxylation of SMX. SMX-HA
      formation in human hepatic microsomes was therefore mediated predominantly by
      CYP2C9. CYP-mediated reduction of SMX-HA to SMX was markedly induced in
      dexamethasone and phenobarbital-treated rat hepatic microsomes, and was
      attributed to CYP3A and CYP2B forms. In uninduced rat and human hepatic
      microsomes, SMX-HA reduction was mediated predominantly by an NADH-dependent
      microsomal hydroxylamine reductase under aerobic conditions. Under anaerobic
      conditions, troleandomycin at > or = 1 microM inhibited the reduction of SMX-HA
      in human hepatic microsomes by 45%, whereas sulfaphenazole had no
      effect.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7628310
TI  - Biliary excretion of pyrrolic metabolites of [14C]monocrotaline in the rat.
AB  - The biliary excretion of amphoteric pyrroles was studied using in situ isolated
      rat liver preparations perfused in a recirculatory manner for 60 to 90 min with
      14C-monocrotaline (40 mumol/120 ml of Krebs-Henseleit buffer). After 90 min, 20%
      of the administered 14C and an amount of pyrrole equivalent to 9 mumol of
      dehydroretronecine was recovered in the bile. Bile collected between 15 and 30
      min contained the highest levels of 14C and pyrrolic metabolites. Isoelectric
      focusing (IEF) and electrophoretic separations on matrices of polyacrylamide and
      silica were used to isolate and estimate levels of pyrrolic conjugates. IEF and
      electrophoretic separations on silica revealed the presence of six pyrrole
      positive metabolites. Reactions of monocrotaline pyrrole with glutathione
      produced three conjugates that had the same pI values as components found in
      bile. Electrophoretic separations on silica and polyacrylamide followed by
      reversed phase chromatography removed sufficient biliary matrix contaminants to
      permit identification of glutathione and cysteinyl-glycine conjugates of 6,7
      dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine and 1-formyl-7-hydroxy-6,7
      dihydro-5H-pyrrolizine with fast atom bombardment MS/MS. This study revealed a
      complexity in the biliary pyrrolic excretion profile that had not previously been
      realized.

PMID- 7628309
TI  - Comparative analysis of cytochrome P4503A induction in primary cultures of rat,
      rabbit, and human hepatocytes.
AB  - We previously demonstrated that induction of hepatic cytochrome P4503A (CYP3A)
      immunoreactive protein is a response in rats, but not rabbits, treated with the
      antiglucocorticoid, pregnenolone 16 alpha-carbonitrile and in rabbits, but not
      rats, treated with rifampicin. These striking interspecies differences in
      response to CYP3A inducers prompted us to compare the effects of a variety of
      agents on CYP3A expression in primary cultures of hepatocytes from rats, rabbits,
      and humans, maintained under nearly identified conditions on Matrigel. We used
      treatment with dexamethasone, the most effective inducer of CYP3A mRNA and CYP3A
      immunoreactive protein in cultures of rat hepatocytes, to define the 100%
      response. As expected from their effects in vivo, incubations of cultures with
      medium containing pregnenolone 16 alpha-carbonitrile or rifampicin induced CYP3A
      mRNA to high levels exclusively in rat hepatocytes or rabbit hepatocytes,
      respectively. Pregnenolone 16 alpha-carbonitrile treatment also did not induce
      CYP3A immunoreactive protein in rabbit hepatocytes, although rifampicin treatment
      did increase CYP3A immunoreactive protein levels in rat hepatocyte cultures.
      Additions of phenobarbital to the cultures induced CYP3A mRNA and CYP3A
      immunoreactive protein to a greater extent in rabbit hepatocytes (94-108% of the
      dexamethasone response) than in rat hepatocytes (38-57% of the dexamethasone
      response). In primary cultures of human hepatocytes, dexamethasone and
      phenobarbital treatments induced CYP3A mRNA (> or = 4.4- and 1.9-fold,
      respectively, over the amounts of CYP3A mRNA in incubated control
      cultures).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7628311
TI  - Induction of catechol-O-methyltransferase in the luminal epithelium of rat uterus
      by progesterone: inhibition by RU-486.

PMID- 7628312
TI  - Formation of chloroethylamine and 1,3-oxazolidine-2-one following ifosfamide
      administration in humans.

PMID- 7628313
TI  - Selectivity of cytochrome P4502E1 in chlorzoxazone 6-hydroxylation.

PMID- 7628314
TI  - [Paroxysmal nocturnal hemoglobinuria. Clinical experiences with 40 patients at
      one center over 25 years].
AB  - In one centre (the medical department of the University of Ulm), over a period of
      25 years, the diagnosis of paroxysmal nocturnal haemoglobinuria (PNH) had been
      made in 40 patients (27 women, 13 men). The data on these patients were analysed
      and the findings compared with those reported in the literature. Criteria for
      inclusion were a positive sucrose haemolysis and acid-serum test. Leading
      clinical symptoms were anaemia, tendency towards bleeding and infections,
      haemolysis, abdominal pain and thromboembolism. The age at which main symptoms
      first appeared was most often in the third and fourth decade of life. The sex
      ratio of 2:1 (female to male) was unusual. PNH was frequently (in 22 patients)
      associated with aplastic anaemia. If bone marrow transplantation, at present the
      only curative procedure, was not possible and there was PNH alone, treatment was
      supportive and directed at relief of symptoms. The course of the disease was
      highly variable. Lack fo prognostic criteria made it difficult to define
      indications for intensive therapeutic measures. While haemolytic crisis and
      thromboembolism are frequent complications in isolated PNH haematopoetic
      insufficiency defines clinical outcome in PNH combined with aplastic anaemia.

PMID- 7628315
TI  - [Arachnoid cyst as the differential diagnosis of ischemic optic neuropathy in
      type-II diabetes].
AB  - HISTORY AND CLINICAL FINDINGS: A 71-year-old woman, a diabetic (type IIb) for 27
      years, developed bilateral hemianopsia over a period of about 2 years. A few
      weeks before hospital admission the defect in her visual fields increased more
      rapidly and double vision occurred intermittently. The hemianopsia was
      demonstrated by finger perimetry. There was no evidence of heart failure or
      peripheral vascular disease. Muscle reflexes were normal, but there was a
      decrease in vibratory sensation in both feet. The cause of the visual disturbance
      was at first thought to be an ischaemic optic neuropathy. INVESTIGATIONS:
      Biochemical tests showed an HbA1 of 12.8%, blood sugar levels were between 230
      and 359 mg/dl, and there was increased intravascular platelet activation.
      Ophthalmological examination confirmed bitemporal hemianopsia and early
      retinopathy. Magnetic resonance imaging of the skull revealed an intra- and
      suprasellar cystic space-occupying lesion extending to the right optic chiasma.
      These findings, taken together, indicated an arachnoidal cyst. TREATMENT AND
      COURSE: After the diabetic metabolic state had been normalized with insulin
      treatment (average of 30 IU of an intermediary insulin) and dietary measures, the
      cyst was evacuated stereotactically. The hemianopsia quickly improved markedly
      and the patient was discharged 4 days after the operation with her vision nearly
      fully restored.

PMID- 7628317
TI  - [The sonographic assessment of the female genitalia. Abdominal and vaginal
      sonography compared].

PMID- 7628316
TI  - [Vaso-occlusive crises in sickle-cell anemia].
AB  - HISTORY AND FINDINGS: Severe pain suddenly occurred in the shaft of the right
      thigh in a 21-year-old patient of Turkish descent with known homozygotic sickle
      cell anaemia. He also had marked scleral jaundice and anaemia (haemoglobin 9.1
      g/dl). An X-ray film of the lower leg pointed to a bone infarct. Type of pain,
      partial pressure of oxygen in blood (70 mm Hg), concentration of lactate
      dehydrogenase and the bilirubin level (4,5 mg/dl) as signs of haemolysis, as well
      as the fall in haemoglobin, indicated a vascular occlusive crisis in sickle cell
      anaemia. TREATMENT AND COURSE: The symptoms regressed within 8 days of the
      patient receiving fluids, analgesics and oxygenation by nasal tube. A few weeks
      later he developed a fever, productive cough and severe pain in joints and
      abdomen. Blood p02 was 54 mm Hg. Pneumonia in the right lung base was the cause
      of this renewed life-threatening crisis, which was again associated with
      haemolysis. Klebsiella having been found in sputum he was treated with cefotaxim
      (1 g twice daily intravenously) and oxygen insufflation via nasal tube (7 l/min).
      His condition quickly improved. CONCLUSIONS: In patients with sickle cell anaemia
      it is important (1) to regard crises as potentially life-threatening conditions,
      (2) to detect and treat infections as possible causes early and (3) to provide
      sufficient oxygen insufflation quickly, especially in pulmonary infections.

PMID- 7628318
TI  - [Octreotide].

PMID- 7628319
TI  - [Lung involvement in liver diseases].

PMID- 7628320
TI  - [The confidentiality duty of the hospital physician versus that of the family
      physician. The judgement of the Munich Higher Regional Court of 17 September
      1992].

PMID- 7628321
TI  - [Is HIV transmissible through insect stings?].

PMID- 7628322
TI  - [The calcium channel blocker--a new addition to the symptomatic therapy of
      multiple sclerosis].

PMID- 7628323
TI  - [Locally applied botulinum toxin in the treatment of achalasia].

PMID- 7628324
TI  - Temporal bone fracture post-tympanoplasty.

PMID- 7628325
TI  - Capillary hemangioma of the vocal cord.

PMID- 7628326
TI  - Intranasal crusting following endoscopic surgery.

PMID- 7628327
TI  - Tuberculous infections of the head and neck.

PMID- 7628328
TI  - An unusual cause of dysphagia following total laryngectomy.
AB  - A case of dysphagia following wide-field total laryngectomy with excision of the
      overlying skin is presented. Initial investigation as to the cause of the
      dysphagia proved fruitless. Mechanical compression of an adequate-sized
      neopharynx by the "band-like effect" created by the skin closure was hypothesized
      to be the etiology of the dysphagia. Release of the scar contracture and
      resurfacing with a pectoralis major myocutaneous flap reestablished an adequate
      sized hypopharynx and normal deglutition.

PMID- 7628329
TI  - A lateral rhinotomy closure technique to prevent alar blunting.
AB  - This paper describes a simple method of closing a lateral rhinotomy incision
      which prevents alar blunting. The problem with the standard methods of incision
      closure is that they will often result in noticeable blunting of the alar crease.
      The study was performed as a retrospective analysis of my closure results. In
      conclusion, this technique provides an easy method of lateral rhinotomy closure
      for optimal cosmetic results.

PMID- 7628330
TI  - Secondary pharyngeal myotomy for tracheoesophageal speech.
AB  - Pharyngeal myotomy in the post-laryngectomy patient has been described to reduce
      pharyngoesophageal spasm and facilitate vocal rehabilitation and
      tracheoesophageal speech. This report describes the complications and speech
      outcomes in 22 consecutive patients who underwent a secondary pharyngeal myotomy.
      The patients were all drawn from a hospital clinic dedicated to voice
      rehabilitation after laryngectomies. Their ages ranged from 54 to 81-years-old
      with a mean of 64. Two patients suffered surgical complications--both had
      pharyngocutaneous fistulas which resolved with conservative management. One
      patient had an incomplete myotomy and was treated with injection of boulinum
      toxin in the pharyngeal plexus. This treatment resulted in good vocalization.
      Seventeen of 22 patients in the study were long-term TEP users, and all of these
      were judged to have good speech quality. Our experience with myotomy for TEP
      speech demonstrates that many patients with pharyngoesophageal spasm can benefit
      from the procedure and successfully phonate. There were several complications
      related to the procedure, but these were successfully managed conservatively and
      without long-term sequela. Pharyngeal myotomy as an adjunct to TEP is useful and
      effective in selected patients.

PMID- 7628331
TI  - A review of absorbable suture materials in head & neck surgery and introduction
      of monocryl: a new absorbable suture.
AB  - Absorbable sutures are used frequently in the practice of surgery yet there have
      been no studies in the literature that review the currently available sutures. A
      newly released suture was used in a series of 80 head and neck patients and the
      results compared to the surgeon's experience with other absorbable suture
      materials. The literature regarding absorbable sutures is reviewed and background
      information on currently available sutures is provided. The tensile strength and
      absorption of various materials are compared. Degree of tissue reactivity in
      animals is presented. Results of the evaluation of Monocryl in 80 cases suggest
      that it has many preferable qualities including ease of handling, low tissue
      reactivity, superior tensile strength, and lower cost.

PMID- 7628332
TI  - Duration of buffered lidocaine versus unbuffered lidocaine: a double-blind,
      randomized prospective study.

PMID- 7628333
TI  - Familial bilateral branchial cleft cysts.

PMID- 7628334
TI  - Head and neck infections in pediatric cardiac transplant patients.
AB  - A retrospective chart review was undertaken at Columbia Presbyterian Medical
      Center to assess the incidence, etiology and management of head and neck
      infections in pediatric cardiac transplant patients on immunosuppression. From
      June 1984 to February 1992, 59 cardiac transplants were performed on 57 pediatric
      patients. Standard immunosuppressive therapy was used. Thirteen of these patients
      died within three months of transplant and were not included. Of the 44 patient
      charts reviewed, 82 head and neck infections were documented in 27 patients
      (61%). There were 26 episodes of sinusitis, 27 episodes of otitis media and 20
      episodes of tonsillitis/pharyngitis. Unusual middle-ear pathogens seen included
      Morganella morgagni and Pseudomonas aeruginosa. These preliminary data suggest
      that children on immunosuppression for cardiac transplant may be at risk for head
      and neck infections from unusual or unsuspected organisms, and tympanocentesis
      plays an important role in diagnosis and treatment. A prospective study is
      planned to gain further data.

PMID- 7628335
TI  - [Refractory Schizophrenias: Assessment and Future Prospects 1995. Sandoz
      symposium, proceedings. Paris, February 3, 1995].

PMID- 7628336
TI  - [Treatment refractory schizophrenia].
AB  - Historically, first case-report of resistant schizophrenia were described under
      insulin therapy. Later on, the development of classical neuroleptics has
      permitted a better outcome but the persistence of a lack of improvement in
      certain patients has induced the individuation of treatment-refractory
      schizophrenia criteria. The difficulties in defining the refractory schizophrenic
      patients are described: variability of the schizophrenia diagnostic criteria,
      variability of outcome, lack of consensus about the good practices in neuroleptic
      treatment, difficulties in defining response criteria and the confusion between
      resistance, chronicity and severity. Three kinds of treatment refractory
      schizophrenia criteria are available: by Kane et al., May et Dencker, Brenner
      Dencker et al. There are few studies including resistant schizophrenic patients:
      their results are not homogeneous, perhaps because the prevalence of treatment
      refractory schizophrenia is poorly known, with ranges from 5 to 25%. The
      following factors are hypothesized as being readily associated to a poor outcome
      and perhaps resistance: male sex, early illness beginning, severity of negative
      or formal thought disorder, absence of an affective syndrome, morphological CT
      scans abnormalities, pharmacological factors, late treatment initiation,
      variability of biodisposibility... Then the therapeutic point of view is
      considered under three main axes: neuroleptic drugs (NLP) are the basis of
      chemotherapy, but other therapeutic approaches complete the biological treatment:
      coherent institutional work and implication of family environment.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7628337
TI  - [Depressive symptoms and negative symptoms during schizophrenia].
AB  - Taking into account the wellknown frequency of depressive and extrapyramidal
      symptoms in schizophrenia and the rare studies about their evolution, several
      questions can be raised: How do these different symptoms move? Are there specific
      characters of each of them? First, stability of negative symptoms evaluated by
      the Scale for the Assessment of Negative Symptoms (SANS) was studied among 57
      schizophrenic patients at admission and at discharge. The course of negative
      symptoms was compared to that of depressive MADRS (Montgomery et Asberg
      Depression Rating Scale) and akinetic symptoms (Extrapyramidal Symptom Rating
      Scale). All the subscores of the SANS decreased significantly but 4 items
      belonging to the affective flattening subscale and one item belonging to the
      alogia subscale did not vary significantly, showing the necessity of taking into
      account the individual items of the SANS rather than the subscale scores to
      evaluate the course of negative symptoms. Changes in all the SANS subscores
      except the alogia and anhedonia subscores were associated with variations in
      scores of other scales. Correlations between the changes of negative symptoms and
      the changes of depressive symptoms showed the necessity to do more specific
      scales, for example, scales for depression in schizophrenia. Langlois-Thery et
      al. (1994) evaluated among 53 schizophrenic patients stabilized with neuroleptic
      treatment, depressive symptomatology with Echelle de Ralentissement Depressif
      (ERD, Widlocher, 1983) and MADRS, negative symptomatology (Positive and Negative
      Syndrome Scale) and akinesia (ESRS), to determinate whether ERD composed of 3
      subscores (motor, ideic and subjective) could be able to evaluate the depressive
      symptomatology, independently of the measures of negative and akinetic
      symptomatology.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7628338
TI  - [Arguments for early treatment of refractory schizophrenia].
AB  - The authors, taking up their experience and the literature, attempt to view the
      precociousness of alternative, classical neuroleptic treatments in schizophrenia,
      from notion of treatment-resistant schizophrenia, precocious refractory and
      intolerance. Until now, clozapine was administrated to patients lasting resistant
      and in mainly cases hospitalized since many years. As such as quality of life and
      economy of health, it would be desirable to quickly think of alternatives
      neuroleptic's therapeutic protocols and clozapine in the treatment-resistant
      schizophrenias or those presenting an intolerance.

PMID- 7628339
TI  - [Psychopharmacologic approaches to schizophrenic psychoses].
AB  - The dopaminergic hypothesis in schizophrenia has progressively shifted to a
      bipolar hypothesis. Furthermore, there are numerous interactions between
      dopaminergic systems and other neurotransmission systems. Therefore, several
      pharmacological approaches are possible either through the specific antagonism of
      different dopaminergic receptors subclasses, partial dopaminergic agonists or
      indirect modulation or through the combined blockade of dopaminergic and
      serotoninergic, cholinergic or adrenergic receptors. The challenge today is to
      link a given clinical effect to one specific pharmacological property.

PMID- 7628340
TI  - [Pharmacologic approach to negative symptoms in schizophrenia].
AB  - Various pharmacologic agents have been reported to be effective in treating
      negative symptoms of schizophrenia. European schools of psychiatry and especially
      the French one assumed the opinion that part of negative symptoms of
      schizophrenia do respond to neuroleptics. In light of effects of reserpine and
      some phenothiazines on negative schizophrenia, various pharmacologic agents have
      been studied focusing on these properties. Various papers devoted to this
      question concluded that some drugs, particularly neuroleptics, can be considered
      as disinhibitors: phenothiazines (thiotixene, trifluoperazine, fluphenazine,
      pipotiazine), butyrophenones (trifluperidol, risperidone),
      diphenylbutylpiperidines (pimozide) and benzamides (sulpiride, amisulpiride).
      Major part of controlled studies concluded to the better efficacy of low doses of
      such drugs on negative symptoms, while high doses are almost inefficient. Some
      studies concluded in the activity of clozapine on negative symptoms of
      schizophrenic patients. To answer the question whether negative symptoms of
      schizophrenia are improved concomitantly or independently of improvement in
      positive symptoms or of decrease in extrapyramidal side effects and/or depressive
      symptoms, the authors prospectively followed up for 30 months, 13 DSM-IV
      resistant schizophrenics. Symptoms were assessed by means of 18 item Brief
      Psychiatric Rating Scale, Positive and Negative Syndrome Scale and Extrapyramidal
      Symptom Rating Scale (ESRS). Improvement in negative symptoms was significantly
      correlated to improvement in positive ones and to scores in ESRS. Many open
      studies concerning anti-depressants and other drugs have been published; however
      controlled studies are necessary to confirm these data.

PMID- 7628341
TI  - [Schizophrenia, affective symptoms and clozapine].
AB  - Clozapine has been shown to be effective in treating schizophrenic patients. In
      this study we compare the efficacy of clozapine in two groups of treatment
      resistant psychotics (among the most severe inpatients). 5 chronic schizophrenics
      (CS). Age 49.6 +/- 12 (paranoid, disorganized residuals). 14 "mixed" patients
      (MP). Age 34.6 +/- 13, between: major affective disorders (MAD) with mood
      incongruent psychotic features; schizo affective disorders (SAD). 19 patients (11
      females -8 males) have been involved in our trial. They receive 400 up to 800
      mg/day of clozapine for a minimum of 12 months and a maximum of 38 months.
      Treatment responders were defined on the evaluation of the following criteria:
      scores PANSS-CGI-MADRS (not for the first patients); number of relapses; response
      to socialisation (exit); quality of life. The results even if based on small
      sample sizes were classified as: Improvement -->reduction of all major symptoms:
      patient exit. CS:2/5 (40%); MP:5/14 (35%). Improvement++-->decrease of most major
      symptoms. CS:1/5 (20%); MP:5/14 (35%). Improvement+-->decrease of one or few
      major symptoms. CS:2/5 (40%); MP: 1/14 (8%). Failure-->3 from the MP subgroup
      (16%), 1 leucopenia, 1 worsening, 1 non responder). These finding show that
      affective disorders and schizoaffective patients are as likely to respond to
      clozapine as the schizophrenic patients: 60% of the CS and 70% of the MP were
      very much ( ) and much improved (++). The data also suggest that in the subtype
      of MP high scores of response occur with the youngest and most recently ill
      patients (< 30 years, < 18 months).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7628342
TI  - [Current data on neurologic sequelae caused by neuroleptics].
AB  - The neurological effects of neuroleptic drugs are well known from the very
      beginning of their history and are even part of the initial definition of this
      therapeutic class. However, these effects are not necessary for an antipsychotic
      efficacy as demonstrated by the fully effective "atypical" neuroleptics, which
      induce minimal neurological side-effects. The neurobiological mechanisms
      underlying this "atypicity" are not well elucidated but could involve a
      preferential action on mesocorticolimbic dopaminergic system. This preferential
      action on mesocorticolimbic dopaminergic system. This specificity of action seem
      especially interesting in the case of patients suffering of severe tardive
      dyskinesia. Hence, the absence of rebond of preexistent dyskinesia when stopping
      a long term treatment with clozapine suggest that the pursuit of neuroleptic with
      this substance in dyskinetic patients would not worsen the long term prognosis of
      their dyskinesia. Available data on other atypical neuroleptics are insufficient
      to conclude if this benefit action on tardive dyskinesia is specific of clozapine
      or shared with other new neuroleptics.

PMID- 7628343
TI  - [Blood clozapine level and therapeutic adjustment].
AB  - We specify first the pharmacokinetic parameters of clozapine and the utilized
      dosage technique. In forty-four patients, aged 40 (25-66), suffering from
      schizophrenia developing for 20 years, with 11 years of hospitalisation.
      Clozapine has been prescribed for at least three months (until 44 months). We
      base ourselves on the opinion of the clinicians to show that the measurement of
      the plasma level can improve therapeutic-results. We analyse different situations
      where the adaptation of the posology is usefully conditioned by clozapinemia,
      particularly in case of important side effects, of high posology (over 600 mg)
      and of non response or inadequate response to the treatment.

PMID- 7628344
TI  - [Hematologic effects of clozapine: evaluation of the international experience].
AB  - Before clozapine was marketed, 4 cases of agranulocytosis occurred amongst the
      2,900 patients exposed to the drug in the clinical studies from 1962 to 1972. At
      that time the frequency of 0.14% was considered comparable to that published with
      some phenothiazines. After clozapine was launched in different countries, several
      notifications of agranulocytosis/granulocytopenia were reported, with a high
      mortality ratio in some countries. This outbreak of agranulocytosis has led to
      the implementation of recommendations, particularly a strict worldwide
      hematologic surveillance with a discontinuation of clozapine when the white blood
      cells drop below a critical level. This article emphasizes the positive impact of
      these precautionary measures on the present incidence of the agranulocytosis and
      on the mortality ratio.

PMID- 7628345
TI  - [Leponex: experience of the hospital pharmacist].
AB  - Clozapine's monitoring, with a co-responsibility between psychiatrists and
      pharmacists, was very efficient for the prevention of neutropenia's side effects.
      This intensive drug safety has lowered the agranulocytosis' cases in France to a
      0.5% prevalence. However the cost of clozapine led to a strict estimation for
      Health expenditures. Our study, trained in an university department of psychiatry
      in Sainte-Anne Hospital (Paris), has included 14 patients treated with clozapine
      during at least 12 months and has displayed a decrease of 10% in their annual
      global cost, comparing to the same group of patients treated by classical
      neuroleptics during the preceding year. This global cost includes the treatment,
      the blood monitoring and the cost of different hospital or community cares.
      Quality of life, in clozapine group, was much improved as illustrated by lowing
      full time hospitalization relayed earlier by community care and precocious social
      readaptation.

PMID- 7628346
TI  - [Medical economic impact of schizophrenia].
AB  - In common with other chronic illness, schizophrenia places a major economic
      burden on society, in terms of direct costs (in and outpatient care, residential
      care, drug therapy, etc.) and indirect costs (lost activity and earnings due to
      illness) and intangible costs (e.g. suffering experienced by the patient and
      family). Of the psychiatric illness, schizophrenia is by far the most costly: it
      develops early in life, results in high morbidity, is associated with a high
      suicide rate, and lacks a standard effective treatment. Analysis of worldwide
      epidemiological studies published during the last 30 years indicates that the
      prevalence of schizophrenia ranges from 0.6 to 9 cases per 1,000 population. The
      prevalence of treatment-resistant schizophrenia ranges from 5 to 30% patients. In
      other hand, clinical options for the management of treatment-resistant
      schizophrenia appears to be limited. Clozapine, an antipsychotic agent with
      relatively weak central antidopaminergic activity, displays atypical
      pharmacological and clinical properties towards the standard antipsychotics.
      Furthermore, clozapine is effective in a substantial proportion of patients who
      are refractory therapy. Although the acquisition cost of clozapine is high in
      comparison with that of standard antipsychotics, preliminary cost-effectiveness
      estimates in patients with treatment-resistant schizophrenia suggest that the
      clinical benefits of the drug (viz improved psychopathology; social functioning
      and quality of life) may confer medium to long term economic benefits, primarily
      by reducing the need for psychiatric hospital service.

PMID- 7628347
TI  - [Clinical psychopharmacology: the example of clozapine (Leponex)].
AB  - Ever since clozapine was discovered, researchers have been attempted to answer
      the question of what makes it different and how to relate its many
      pharmacological actions to its clinical features. Its clinical profile conflicts
      with the hypothesis that antipsychotic effect is due entirely to D2 dopamine
      receptor blockade. Clozapine is known to interact with many neurotransmitters
      systems. To date, four main hypothesis have been proposed in an attempt to
      explain some or all for clozapine's atypical properties: selective blockade of
      mesolimbic dopamine function; D1, D2, D3 and D4 receptor blockade; 5-HT2 and D2
      receptor blockade; Potent alpha 1 adrenergic blockade. These hypothesis are
      reviewed in relation to the clozapine clinical profile. No hypothesis fully
      accounts for clozapine's spectrum of neurotransmitter interactions. Such a
      multiplicity of action would preclude a unified mechanism.

PMID- 7628348
TI  - Thyroglobulin--a new cyclic adenosine monophosphate-dependent protein kinase?

PMID- 7628349
TI  - Evidence that thyroglobulin has an associated protein kinase activity correlated
      with the presence of an adenosine triphosphate binding site.
AB  - 19S Thyroglobulin (Tg), a dimeric glycoprotein with an M(r) of 660,000, was
      extracted from rat, bovine, and human (goitrous) thyroid tissues, as well as from
      culture medium of FRTL5 rat thyroid cells. Subjected to rigorous purification
      procedures, all Tg preparations showed a protein kinase activity that is able to
      phosphorylate serine residues in vitro. Further characterization of this
      enzymatic activity revealed that Tg has the specificities of a protein kinase A
      when Kemptide was used as specific substrate and after analysis of cAMP
      stimulated phosphotransferase activity in all Tg preparations tested.
      Furthermore, Tg contains a specific and saturable ATP binding site, as evidenced
      by specific binding with the ATP affinity analog p-fluorosulfonylbenzoyl 5'-p
      adenosine (FSO2BzAdo). Limited proteolysis of FSO2[14C]BzAdo-labeled human goiter
      Tg with clostripain gave rise to a M(r) 64,000 amino terminal polypeptide
      carrying almost all of the label. The analysis of this fragment revealed two
      sequences that may play an analogous phosphate-loop (P-loop) function, even
      though their primary sequences differ slightly from the classical A consensus
      sequence or P-loop. The ATP binding site of Tg may be functionally associated
      with the presence of a protein kinase A phosphorylating activity linked to the Tg
      itself, because the addition of the analog is able to inhibit the enzymatic
      activity in a dose-dependent fashion. Contamination with non-Tg phosphorylase
      cannot be ruled out at present, even though the amount of ATP that Tg was able to
      bind did not significantly change during the various purification steps. Together
      these findings favor the hypothesis that the Tg molecule contains a protein
      kinase activity that is capable of autophosphorylation.

PMID- 7628350
TI  - Involvement of interleukin-1 and interleukin-1 receptor antagonist in rat
      pituitary cell growth regulation.
AB  - Interleukin-1 (IL-1), one of the mediators of the interaction between the immune
      and the neuroendocrine system, is well known to modulate anterior pituitary
      hormone secretion. As IL-1 influences growth of various cell types, we
      investigated whether IL-1 is also a growth factor of pituitary cells. We
      demonstrate that IL-1 dose and time dependently inhibits the growth of normal rat
      pituitary cells under serum-free conditions. The inhibitory potencies of IL-1
      alpha (ED50, 8 pg/ml) and IL-1 beta (ED50, 6 pg/ml) were nearly identical. In the
      presence of low amounts of serum, both IL-1 alpha (ED50, 130 pg/ml) and IL-1 beta
      (ED50, 90 pg/ml) were less effective in inhibiting growth. The IL-1-induced
      growth inhibition was IL-1 receptor mediated, because both IL-1 alpha- and IL-1
      beta-mediated growth suppression could be completely reversed by the IL-1
      receptor antagonist, the physiological counterpart of IL-1. In the
      mammosomatotroph GH3 rat pituitary tumor cell line, IL-1 failed to influence
      growth, indicating that either IL-1 receptors are missing or the IL-1 signaling
      pathway is uncoupled from the growth regulation. In contrast to growth, in our
      rat pituitary monolayer cell culture system, IL-1 did not affect ACTH, GH, or PRL
      secretion as described previously. This discrepancy suggests the involvement of
      different mechanisms in the IL-1-induced mediation of growth and hormone
      secretion.

PMID- 7628351
TI  - Repression of endogenous estrogen receptor activity in MCF-7 human breast cancer
      cells by dominant negative estrogen receptors.
AB  - We have investigated the ability of several transcriptionally inactive estrogen
      receptor (ER) mutants to block endogenous ER-mediated transcription in MCF-7
      human breast cancer cells. In transient transfections of MCF-7 cells, two of the
      mutants, a frame-shifted ER (S554fs) and a point-mutated ER (L540Q), strongly
      inhibit the ability of endogenous wild-type ER to activate transcription of
      estrogen-regulated reporter plasmids. A third mutant, ER1-530, which is missing
      65 residues from its carboxy-terminus, is a weaker repressor of estradiol
      stimulated transcription. When an estrogen response element (ERE)-thymidine
      kinase-chloramphenicol acetyltransferase reporter gene is used, S554fs, L540Q,
      and ER1-530 suppress the transcriptional activity of endogenous MCF-7 ER by 87%,
      97%, and 62%, respectively. The magnitude of dominant negative repression is
      promoter specific; when an ERE-pS2-chloramphenicol acetyltransferase reporter is
      employed, inhibition of endogenous ER activity by equivalent amounts of S554fs,
      L540Q, and ER1-530 ranges from 85-97%. Dose-response studies show the S554fs
      mutant to be the most potent of the three ER mutants as a repressor of estrogen
      action in these cells. In addition, elevated levels of intracellular cAMP,
      achieved by the addition of 3-isobutyl-1-methylxanthine plus cholera toxin to
      cells, fail to compromise the effectiveness of these mutants as dominant negative
      ERs despite the cAMP-enhanced transcriptional activity of ER. The mutants are
      also powerful repressors of the agonist activity of trans-hydroxytamoxifen
      stimulated ER transcription. The dominant negative activity of the three mutants
      is lost when the A/B domain of these receptors is deleted, implying an important
      role for this N-terminal region of the ER in the ability of these mutants to
      inhibit endogenous wild-type ER activity. All in all, the data suggest that
      S554fs in particular is a reasonable candidate for studies designed to use a
      dominant negative ER to inhibit the estrogen- and tamoxifen-stimulated growth of
      human breast cancer cells.

PMID- 7628352
TI  - Expression of the citrulline-nitric oxide cycle in rodent and human pancreatic
      beta-cells: induction of argininosuccinate synthetase by cytokines.
AB  - Nitric oxide (NO) may be a mediator of beta-cell damage in insulin-dependent
      diabetes mellitus. beta-Cells express the inducible form of NO synthase (iNOS)
      and produce large amounts of NO upon exposure to cytokines. iNOS requires the
      amino acid arginine for NO formation. It has been shown in other cell types that
      interferon-gamma (IFN gamma) and bacterial lipopolysaccharide induce the enzyme
      argininosuccinate synthetase (AS), enhancing the capacity of these cells to
      regenerate arginine from citrulline and maintain NO production in the presence of
      low arginine concentrations. To characterize the messenger RNA (mRNA) expression
      of AS in insulin-producing cells, RINm5F cells (RIN cells) were exposed to
      interleukin-1 beta (IL-1 beta) or to tumor necrosis factor-alpha plus IFN gamma.
      After 4-6 h, there was a significant and parallel induction of AS and iNOS mRNA.
      IL-1 beta-induced AS and iNOS mRNA expression was prevented by an inhibitor of
      the activation factor NF-kappa B pyrrolidine diaminoguanidine, an inhibitor of
      gene transcription (actinomycin D), and a blocker of protein synthesis
      (cycloheximide), suggesting coregulation of AS and iNOS by cytokines. RIN cells
      exposed to IL-1 beta in the presence of citrulline but the absence of arginine
      had increased AS enzyme activity and produced NO, demonstrating that cytokine
      induced AS mRNA expression is accompanied by increased AS activity. Both adult
      rat islets exposed to IL-1 beta and human pancreatic islets cultured in the
      presence of IL-1 beta, tumor necrosis factor-alpha, and IFN gamma were able to
      use citrulline to regenerate arginine and produce NO. Taken as a whole, the
      present data suggest that regulation of AS activity may play a role in modulation
      of NO production in both rodent and human insulin-producing cells.

PMID- 7628353
TI  - Effects of parathyroid hormone (PTH)-related protein and PTH on osteoclasts and
      osteoclast precursors in vivo.
AB  - Increased production of PTH-related protein (PTHrP) and PTH is frequently
      responsible for hypercalcemia and its associated morbidity. However, it is
      unclear whether these peptides produce identical effects on cells in the
      osteoclast lineage in vivo. To examine the effects of continuous in vivo exposure
      to these factors on both the osteoclast precursors and mature osteoclasts, we
      inoculated Chinese hamster ovarian cells expressing PTH-(1-84), PTHrP-(1-141), or
      nontransfected Chinese hamster ovarian cells into nude mice. The effects of these
      tumors on blood ionized calcium, plasma PTH and PTHrP concentrations, and
      osteoclast formation were then determined. PTH and PTHrP tumor-bearing mice
      became hypercalcemic (1.90 +/- 0.04 and 1.97 +/- 0.16 mmol/liter, respectively)
      compared with control mice (1.29 +/- 0.015 mmol/liter). After 4 days of
      hypercalcemia, mice were killed, and bone marrow cells were harvested to examine
      cells at three discrete stages of osteoclast development: multipotent osteoclast
      precursors, the granulocyte/macrophage colony-forming unit; more committed marrow
      mononuclear osteoclast precursors; and mature osteoclasts. Neither PTH nor PTHrP
      had an effect on granulocyte/macrophage colony-forming unit, but similarly
      increased the number of more committed mononuclear osteoclast progenitors as well
      as mature osteoclasts in the calvaria. No differences were detected between the
      effects of PTH and PTHrP on cells in the osteoclast lineage in vivo. Thus, PTH
      and PTHrP appear to affect only more differentiated cells in the osteoclast
      lineage, and the differences in osteoclastic bone resorption between primary
      hyperparathyroidism and humoral hypercalcemia of malignancy are probably due to
      mechanisms other than effects on osteoclast precursor cells in vivo.

PMID- 7628354
TI  - Distribution and hormonal regulation of androgen receptor (AR) and AR messenger
      ribonucleic acid in the rat hippocampus.
AB  - The actions of androgens in both peripheral and central tissues are linked in
      part to their ability to specifically bind and activate androgen receptors (ARs).
      ARs have been well studied in the rat hypothalamus and peripheral reproductive
      tissues, where they are directly involved in endocrine feedback mechanisms and
      reproduction. Previous studies revealed relatively high levels of AR and AR
      messenger RNA (mRNA) in the rat hippocampus; however, the action of androgen in
      this brain region remains unclear. To begin to address this issue, we used a
      multidisciplinary approach to quantitate hippocampal AR and AR mRNA levels and
      investigate their regulation after various hormonal manipulations. In vitro
      binding assays revealed a single, saturable, high affinity binding site for
      androgen in hippocampal cytosols. The expression of AR mRNA in the intact adult
      male rat hypothalamus and hippocampus was demonstrated using reverse
      transcription-polymerase chain reaction and quantified using a ribonuclease
      protection assay. Comparable levels of AR mRNA were found in the hippocampus and
      hypothalamus. In addition, in situ hybridization analysis revealed a unique
      distribution of AR mRNA in the hippocampus. AR mRNA was found predominately in
      the CA1 pyramidal cells, which form the major signal output of the hippocampal
      trisynaptic circuit. Reverse transcription-polymerase chain reaction of total RNA
      from microdissected hippocampal regions confirmed this distribution. Ribonuclease
      protection assay demonstrated a significant decrease in the AR mRNA content of
      the hippocampus in animals killed 4 days after castration or in intact rats after
      four daily injections of the AR antagonist, flutamide (15 mg/animal), compared to
      that in intact controls (P < 0.01). In contrast, a 35% increase (P < 0.05) in the
      hippocampal AR mRNA content was found in old (22-month-old) compared to young (5
      month-old) male rats. In both cases, [3H]dihydrotestosterone binding to the
      cytosolic preparation did not parallel the changes observed in the AR mRNA
      content. Taken together, these data demonstrate that hippocampal cells containing
      AR can respond to circulating androgen to alter AR gene expression. Furthermore,
      AR mRNA autoregulation appears to be both age and tissue specific and does not
      directly follow the regulatory patterns described for other steroid hormone
      receptors found in the hippocampus.

PMID- 7628355
TI  - Prostaglandin F2 alpha stimulates transforming growth factor-alpha expression in
      adipocyte precursors.
AB  - Transforming growth factor-alpha (TGF alpha) and prostaglandin F2 alpha (PGF2
      alpha) are potent inhibitors of adipocyte differentiation. We demonstrate here
      that TGF alpha messenger RNA (mRNA) is expressed in freshly isolated fat pads and
      in primary culture of adipocyte precursors cultivated in defined medium before
      and after differentiation. We show that PGF2 alpha stimulated TGF alpha mRNA
      expression in a dose-dependent manner. PGF2 alpha also stimulated TGF alpha
      production in the culture medium of adipocyte precursors in primary culture. PGF2
      alpha stimulated TGF alpha mRNA expression in both undifferentiated and
      differentiated cells. 9 alpha,11 beta-PGF2 alpha, which also inhibited adipose
      differentiation, stimulated TGF alpha mRNA expression similarly to PGF2 alpha,
      whereas other PGs had no effect on TGF alpha mRNA expression. The time-course
      experiment indicates that the stimulation of TGF alpha mRNA expression by PGF2
      alpha is observed within 6 h of exposure to PGF2 alpha and is inhibited by
      treatment of the cells with actinomycin D. The effect of PGF2 alpha on TGF alpha
      expression did not require activation of protein kinase C and was fully
      reversible. As both TGF alpha and PGF2 alpha are inhibitors of adipose
      differentiation, it is suggested that stimulation of TGF alpha expression by PGF2
      alpha could represent an amplification mechanism to modulate adipocyte precursor
      differentiation and adipocyte function within the adipose tissue.

PMID- 7628356
TI  - Luteinizing hormone (LH)-releasing hormone in third ventricular cerebrospinal
      fluid of the ewe: correlation with LH pulses and the LH surge.
AB  - Morphological evidence suggests that LHRH may be secreted into cerebrospinal
      fluid (CSF), but only in the rhesus monkey has CSF LHRH been found to reflect
      changes occurring in the LHRH neuroendocrine system. This study investigated
      whether LHRH is detectable in ovine CSF and, if so, whether its release profile
      correlates with peripheral LH profiles during pulse and surge conditions. A
      polyethylene catheter was threaded through a stainless steel guide cannula
      previously implanted into the third ventricle of an ovariectomized ewe, which
      enabled continuous CSF withdrawal on repeated occasions. The first experiment (n
      = 3) showed that peripheral LH concentrations were unaffected by CSF removal at
      rates of 12, 30, 50, and 100 microliters/min, and the second (n = 4) established
      that CSF LHRH secretion was pulsatile, with considerable variation in pulse
      amplitude (6.3 +/- 1.8 pg/ml; range, 1.3-18.7 pg/ml). In the third experiment (n
      = 6), an endogenous LH surge was induced after progesterone withdrawal and 17
      beta-estradiol administration. Although CSF LHRH (15.3 +/- 1.3 h) and peripheral
      LH (14.8 +/- 1.0 h) surges occurred simultaneously, CSF LHRH concentrations were
      greater than half-maximal levels for longer (11.0 +/- 0.6 h; P < 0.005) than LH
      concentrations (6.0 +/- 0.4 h). This is the first study in sheep to reveal the
      presence of LHRH in CSF and show that it expresses dynamic and longer term
      changes coincident with peripheral LH fluctuations. CSF LHRH analysis also
      permits repeated sampling from individuals and, therefore, long term within
      individual comparisons.

PMID- 7628357
TI  - Regulation of 3 beta-hydroxysteroid dehydrogenase delta 5/delta 4-isomerase and
      cholesterol side-chain cleavage cytochrome P450 by activin in rat granulosa
      cells.
AB  - Activin is a dimeric protein implicated in the local control of follicular
      steroidogenesis. Using cultured rat granulosa cells, we previously showed that
      the effect of activin on FSH-induced progesterone synthesis changes with
      preovulatory follicular development, from positive regulation in
      nondifferentiated (immature) granulosa cells to negative regulation in
      preovulatory (mature) granulosa cells. The aim of the present study was to assess
      development-related effects of activin on the expression of enzymes crucial to
      progesterone synthesis: cholesterol side-chain cleavage cytochrome P450 (P450scc)
      and 3 beta-hydroxysteroid dehydrogenase/delta 5-4-isomerase (3 beta HSD).
      Nondifferentiated granulosa cells were isolated from the ovaries of estrogen
      pretreated immature female rats that received no other treatment; differentiated
      granulosa cells were obtained from similar animals treated for 48 h with human
      FSH to induce preovulatory follicular development. Cells were cultured for 48 h
      in serum-free medium with and without human FSH and/or recombinant activin-A, and
      medium was collected for measurement of progestagens (progesterone, pregnenolone,
      and 20 alpha-dihydroprogesterone). In cultures of nondifferentiated granulosa
      cells, activin augmented the FSH-induced production of all three steroids. In
      differentiated granulosa cells, activin suppressed the FSH-stimulated production
      of progesterone and 20 alpha-dihydroprogesterone, but had no effect on
      pregnenolone. The presence of exogenous pregnenolone increased the overall
      production of progesterone, but did not alter qualitative steroidogenic responses
      to activin. To assess the interaction between FSH and activin on 3 beta HSD and
      P450scc messenger RNA (mRNA) expression, Northern blot analyses were performed on
      total RNA isolated from cultured granulosa cells. Treatment in vitro with FSH
      alone markedly enhanced the abundance of both the 3 beta HSD and P450scc mRNA
      transcripts in nondifferentiated and differentiated granulosa cells. FSH
      stimulated expression of P450scc mRNA was further enhanced by cotreatment of
      nondifferentiated granulosa cells with activin. However, activin had no
      consistent effect on FSH-stimulated expression of 3 beta HSD mRNA in
      nondifferentiated cells. In differentiated granulosa cells, both mRNAs were
      suppressed more than 50% by the presence of activin. We conclude that the in
      vitro effects of activin on FSH-induced expression of 3 beta HSD and P450scc
      mRNAs in rat GC are similar: initially stimulatory (P450scc) or without effect (3
      beta HSD), then becoming completely inhibitory. The mechanism of this development
      dependent change in the granulosa cell response to activin remains to be
      elucidated.

PMID- 7628358
TI  - Evidence for the involvement of chromaffin cells in the stimulatory effect of
      tachykinins on corticosteroid secretion by the frog adrenal gland.
AB  - The adrenal gland of the frog is innervated by a network of fibers containing two
      tachykinins (ranakinin and [Leu3,Ile7]neurokinin A), which both stimulate
      corticosteroid secretion from frog adrenal tissue. The aim of the present study
      was to determine the mode of action of tachykinins on the frog adrenal gland.
      Double immunolabeling of tissue sections with a monoclonal antibody to tyrosine
      hydroxylase and an antiserum to substance P showed that tachykinin-containing
      fibers are preferentially apposed onto chromaffin cells. Immunocytochemical
      labeling at the electron microscope level revealed that tachykinin-immunoreactive
      fibers establish close contacts only with adrenochromaffin cells. Ranakinin
      stimulated corticosterone and aldosterone secretion from perifused adrenal
      slices, but had no stimulative effect on dispersed adrenal cells.
      Cytoautoradiographic labeling of frog adrenal cells in primary culture with
      [3H]substance P revealed the existence of specific binding sites located
      exclusively on chromaffin cells. Microfluorimetric measurement of cytosolic
      calcium concentrations ([Ca2+]i) in cultured adrenal cells showed that ranakinin
      induced a dose-dependent increase in [Ca2+]i in chromaffin cells (ED50 = 2 x 10(
      7) M). In contrast, ranakinin did not affect [Ca2+]i in adrenocortical cells. The
      present results indicate that in the frog adrenal gland, tachykinin-containing
      fibers make preferential contacts with chromaffin cells, and tachykinins directly
      activate chromaffin cells. These data suggest that the stimulative effect of
      tachykinins on corticosteroid secretion is mediated via presynaptic activation of
      adrenochromaffin cells.

PMID- 7628359
TI  - Down-regulation of the receptor for parathyroid hormone (PTH) and PTH-related
      peptide by transforming growth factor-beta in primary fetal rat osteoblasts.
AB  - We studied the effects of transforming growth factor-beta 2 (TGF beta 2) on the
      level of PTH/PTH-related peptide-(PTHrP) receptor messenger RNA (mRNA), PTHrP
      binding, and PTH-stimulated cAMP accumulation in cultured osteoblasts derived
      from fetal rat calvariae (ROB). When ROB were pretreated with TGF beta 2 at
      concentrations ranging from 1-100 pM for 24 h, dose-dependent decreases in the
      level of PTH/PTHrP receptor mRNA, PTHrP binding, and PTH-stimulated cAMP
      accumulation were observed. For the PTH/PTHrP receptor mRNA level and PTH
      stimulated cAMP accumulation, the half-maximal effective concentration was
      approximately 4 pM. For the inhibition of PTHrP binding, the half-maximal
      effective concentration was much higher. A 50% decrease in both PTH/PTHrP
      receptor mRNA level and PTH-stimulated cAMP accumulation was obtained when ROB
      were treated with 100 pM TGF beta 2 for 4 h. A comparable decrease in PTHrP
      binding was only observed after 24 h of incubation with 100 pM TGF beta 2.
      Actinomycin D induced a rapid decrease in the PTH/PTHrP receptor mRNA level (70%
      after 4 h), indicating a half-life for the receptor mRNA of 2-3 h. Under the same
      conditions, PTHrP binding and PTH-stimulated cAMP accumulation did not change.
      When ROB were treated with cycloheximide for the same period, only a small
      decrease in PTHrP binding (20%) was observed, suggesting that PTH/PTHrP receptors
      do not have a rapid turnover. Cycloheximide also reduced PTH-stimulated cAMP
      production; after coincubation of cycloheximide with TGF beta 2, this inhibition
      was smaller than that in ROB cultures treated with TGF beta 2 exclusively. From
      these observations we conclude that TGF beta 2 induces a decrease in steady state
      levels of PTH/PTHrP receptor mRNA that results in decreased PTHrP receptor
      binding. The PTH-stimulated cAMP accumulation is at least to some extent
      independent of the PTH/PTHrP receptor availability. Furthermore, there is a high
      turnover of PTH/PTHrP receptor mRNA, whereas turnover of the receptor protein is
      much slower. Finally, protein synthesis is required for TGF beta 2-induced
      desensitization of cAMP responsiveness to PTH.

PMID- 7628360
TI  - Effects of thyroid hormone on norepinephrine signaling in brown adipose tissue.
      I. Beta 1- and beta 2-adrenergic receptors and cyclic adenosine 3',5'
      monophosphate generation.
AB  - Brown adipose tissue (BAT) thermogenesis is activated by the sympathetic nervous
      system. BAT responses to norepinephrine are blunted in hypothyroidism and are
      rapidly restored by thyroid hormone. We examined in rats the effects of thyroid
      hormone on BAT beta 1- and beta 2-adrenergic receptors (AR) expression and
      capacity to generate cAMP in response to adrenergic stimulation. Both are reduced
      in hypothyroidism. The reduction in cAMP generation is equal to or greater than
      that in beta 1,2-AR; it is the same whether cAMP production is stimulated with
      norepinephrine, selective beta 3-AR agonists, or forskolin; and it is not
      affected by the inhibition of phosphodiesterase. Both beta 1,2-AR and the
      capacity to generate cAMP were slowly corrected by thyroid hormone. T3 normalized
      beta 1,2-AR between 1 and 2 days, whereas the improvement in cAMP generation
      lagged 1 or 2 days behind. Within 2 days of acclimation of athyreotic rats at 30
      C, the number of beta 1,2-AR reached the euthyroid level, whereas exposure to 4 C
      decreased these receptors. We reached the following conclusions: 1) BAT beta 1,2
      AR and capacity to generate cAMP are reduced in hypothyroidism; 2) the latter,
      however, is not explained by the reduction in beta 1,2-AR, but, rather, reflects
      a fault at the postreceptor level; 3) the reduction in beta 1.2-AR number is
      largely caused by the cold stress derived from the low metabolic rate of the
      hypothyroid state; and 4) the slow restoration of both receptor number and
      capacity to generate cAMP after T3 are not consistent with these defects being a
      significant factor in the previously reported blunted uncoupling protein
      responses to adrenergic stimulation in hypothyroidism.

PMID- 7628361
TI  - Thyroid hormone and norepinephrine signaling in brown adipose tissue. II:
      Differential effects of thyroid hormone on beta 3-adrenergic receptors in brown
      and white adipose tissue.
AB  - beta 3-adrenergic receptors (AR) are predominantly expressed in brown (BAT) and
      white adipose tissue (WAT), being more abundant in the former. There is growing
      interest in these receptors because of their potential to be pharmacologically
      targeted to control energy expenditure and lipid accretion. We have examined, in
      BAT and WAT of rats, the effect of thyroid hormone on the expression of beta 3-AR
      and their contribution to cAMP generation. Receptor density was assessed with the
      nonselective beta 3-AR ligand [125I]-cyanopindolol ([125I]-CYP) and the highly
      selective beta 3-AR agonist CL3216,243. beta 3-AR messenger RNA (mRNA) was
      analyzed by Northern blotting of total BAT and WAT RNA. Generation of cAMP by
      brown adipocytes in response to norepinephrine (NE) and CL316,243 was measured by
      RIA. In BAT, beta 3-AR can account for as much as 50% of the maximal cAMP
      response to NE, whereas in WAT these receptors probably account for all the
      effect of NE. In hypothyroidism. BAT beta 3-AR number is increased, as are beta 3
      AR mRNA (4- to 6-fold) and the relative contribution of these receptors to the
      maximal cAMP production. In contrast, both beta 3-AR number and mRNA levels are
      reduced in WAT of hypothyroid rats. The injection of T3 to hypothyroid rats
      reverts the changes in beta 3-AR within 24 h, and T3 excess causes a greater than
      90% reduction in beta 3-AR mRNA in BAT but a 5-fold increase in WAT. In both
      tissues, hypothyroidism is associated with a marked reduction in the capacity to
      generate cAMP, but this is not completely restored even after 2 days of a
      receptor-saturating dose of T3. CONCLUSIONS: 1) thyroid hormone differentially
      affects the expression of beta 3-AR in BAT and WAT; 2) these effects of T3 are
      both rapid and marked and seem to take place at a pretranslational level; 3) in
      both tissues there is a postreceptor defect in the generation of cAMP that is
      corrected by T3 much later after the changes in beta 3-AR are reversed; and 4)
      thyroid hormone is among the known factors that most vigorously affect the
      expression of beta 3-AR.

PMID- 7628362
TI  - Testosterone inhibits and induces apoptosis in rat seminiferous tubules in a
      stage-specific manner: in situ quantification in squash preparations after
      administration of ethane dimethane sulfonate.
AB  - The quantitative effects of ethane dimethane sulfonate (EDS), a Leydig cell
      toxin, on apoptosis in adult rat seminiferous epithelium were studied by the
      improved transillumination method. Nonradioactive in situ end labeling of
      fragmented DNA in squash preparations revealed significant increases in apoptotic
      cells in stages II-XI, whereas controls showed 0.5-2.3 apoptotic cells/mm tubule.
      Seven days post-EDS treatment, the highest numbers of apoptotic cells were scored
      in stages VIIab and VIIcd (74.7 +/- 23.8 and 61.3 +/- 16.0 cells/mm,
      respectively). The effects were suppressed by testosterone (T) supplementation,
      except in stages II-III and VIIcd. An opposite effect was found in stage XII,
      where the number of apoptotic cells decreased 1, 3, and 7 days after EDS
      treatment and returned to control levels in T-supplemented rats. Electrophoretic
      analysis of internucleosomal DNA fragmentation revealed a biphasic apoptotic
      process after 1 and 5-7 days due to Leydig and germ cell apoptosis, respectively.
      The specific germ cell apoptosis was also confirmed by electron microscopic
      analysis. The results suggest that T withdrawal induces apoptotic cell death in
      most stages of the cycle and that the effects are largely preventable. In stage
      XII, however, T seems to promote apoptosis in premeiotic cells.

PMID- 7628363
TI  - Modulation of the activity of glucose transporters (GLUT) in the aged/obese rat
      adipocyte: suppressed function, but enhanced intrinsic activity of GLUT.
AB  - To study the contribution of glucose transporters (GLUT) to insulin resistance in
      aging, GLUT intrinsic activity was assessed in a cell-free system. Adipocytes
      were isolated from 18-month-old rats and young controls and incubated either with
      or without 7 nM insulin. Plasma membrane (PM) and low density microsomal
      fractions were prepared from the cells, and GLUT levels were assessed in these
      fractions before and after reconstitution into liposomes. Glucose transport rates
      were measured in intact cells and liposomes. Functional and intrinsic activities
      of GLUT were assessed from the ratio between these transport rates and GLUT
      levels in the respective fractions. Basal 3-O-methylglucose transport rates were
      unaffected by aging, which is consistent with unchanged levels of GLUT in PM.
      Insulin-stimulated glucose transport was 60% lower in aging, as was the extent of
      GLUT recruitment to PM. The effect of insulin stimulation of GLUT functional
      activity by 6-fold at PM was attenuated by 40% in aging. Conversely, the basal
      intrinsic activity of GLUT was significantly enhanced in aging (by 280% and 230%
      in PM and density microsomal liposomes, respectively) and was further stimulated
      by insulin by about 160% in PM, compared to only about 117% stimulation in
      controls. In conclusion, our data show that insulin stimulates the intrinsic
      activity of GLUT in rat adipocytes, and this activity is further enhanced in
      aging. Impaired glucose uptake in aging can be attributed to depleted GLUT4
      levels and impaired function of GLUT at the cell surface. The discrepancy
      observed between impaired function and enhanced intrinsic activity of GLUT
      suggests the presence of additional factors that modulate the full functional
      expression of GLUT at the cell surface.

PMID- 7628364
TI  - Increased expression of corticotropin-releasing hormone and vasopressin messenger
      ribonucleic acid (mRNA) in the hypothalamic paraventricular nucleus during
      repeated stress: association with reduction in glucocorticoid receptor mRNA
      levels.
AB  - Hypothalamic-pituitary-adrenal (HPA) responses remain intact or increase after
      chronic or repeated stress despite robust levels of circulating glucocorticoids
      that would be expected to restrain the responsiveness of the axis. The purpose of
      this study was to determine whether chronic stress altered corticosteroid
      receptor messenger RNA (mRNA) levels at any locus known to mediate glucocorticoid
      feedback on HPA function (i.e. hippocampus or hypothalamus), whether such effects
      were glucocorticoid dependent, and whether changes in corticosteroid receptor
      function could potentially contribute to the putative shift from corticotropin
      releasing hormone (CRH) to arginine vasopressin (AVP) in the hypothalamic
      paraventricular nucleus (PVN) in the modulation of pituitary adrenal function
      occurring during chronic stress. We compared the stress responsiveness of sham
      operated rats to that of adrenalectomized rats using a moderate dose of
      corticosterone (CORT) pellet replacement (ADX + CORT group). Acute immobilization
      caused a significant increase in CRH, but not AVP, mRNA levels in the
      parvocellular PVN in sham rats. The ADX + CORT group showed significantly greater
      increases in both CRH and AVP mRNA levels in the PVN compared to sham rats. These
      data indicate that PVN AVP mRNA levels are more sensitive to glucocorticoid
      negative feedback than are the levels of CRH mRNA. In repeated stress, the sham
      groups showed robust increases in PVN CRH and AVP mRNA levels despite high levels
      of plasma CORT. The rise in AVP mRNA levels was greater than that in CRH mRNA.
      Type II glucocorticoid receptor mRNA in the hippocampus and PVN was decreased in
      the repeatedly stressed sham group. These data suggest a decrease in the CORT
      negative feedback restraint of PVN CRH and AVP mRNA levels repeated stress and a
      persistence of relatively greater responsiveness of AVP mRNA levels to CORT
      negative feedback. After repeated stress in ADX+CORT rats, both PVN CRH and AVP
      mRNA levels showed robust responses, with a relatively greater increase in AVP
      mRNA. These data indicate that a CORT-mediated decrease in hippocampal and
      hypothalamic glucocorticoid receptor mRNA levels is not the only mechanism
      contributing to the maintenance of a robust HPA response after repeated stress.
      Similarly, we postulate that the relative shift from CRH to AVP in the PVN after
      repeated stress is mediated by both a greater sensitivity of AVP to CORT negative
      feedback and CORT-independent mechanisms.

PMID- 7628365
TI  - Obesity and dehydroepiandrosterone/dehydroepiandrosterone sulfate relationships
      in lean, obese, and meat-type cross-bred boars: responses to porcine growth
      hormone.
AB  - As so many variables can affect obesity (age, genetics, health status), new
      directions, other than reducing or altering diet, are being pursued in
      controlling obesity in our society. Both dehydroepiandrosterone (DHEA) and GH
      have reported antiobesity effects; thus, the possible interaction of these
      hormones was investigated in genetically lean, obese, and meat-type cross-bred
      male pigs (boars) administered implants that released 0, 2, or 4 mg/day
      recombinant porcine GH (pGH) for 42 days. Subcutaneous fat was determined by
      measurement of back fat depth at 2-week intervals, and blood samples were
      obtained 0, 7, 14, 28, and 42 days post-implant. The weight of perinephrenic fat,
      an index of abdominal fat, was obtained at death. The obese line had higher
      DHEA/DHEA sulfate (DHEA-SO4) serum concentrations than the lean and cross-bred
      boars. Treatment with pGH reduced sc and perinephrenic fat in all lines at both
      doses (P < 0.01). There was no relationship between day 42 concentrations of
      DHEA/DHEA-SO4 and indexes of obesity. Concentrations of DHEA/DHEA-SO4 were
      decreased by pGH treatment (P < 0.01) by days 7-14 in all genetic lines.
      Concentrations of insulin-like growth factor I, insulin-like growth factor II,
      and insulin were increased with pGH treatment in all lines (P < 0.01). The a
      priori hypothesis that increases in these peptides would stimulate gonadal
      steroidal synthesis (as demonstrated in vitro) and result in elevated DHEA/DHEA
      SO4 concentrations and reduced obesity was not supported by pGH-induced decreases
      in DHEA/DHEA-SO4. Insulin concentrations were elevated 7-14 days postimplant in
      all lines (P < 0.01), then declined in the later stages of the trial. Insulin
      concentrations and DHEA/DHEA-SO4 concentrations were inversely related (r = 
      0.59; P < 0.05); this may indicate that with elevated insulin levels, DHEA/DHEA
      SO4 is decreased and has a limited opportunity to affect obesity. Although the
      administration of DHEA may reduce obesity, the lipolytic action of pGH does not
      appear to be through increased circulating concentrations of DHEA/DHEA-SO4.

PMID- 7628366
TI  - Parallel insulin-like growth factor I and insulin resistance in muscles of rats
      fed a high fat diet.
AB  - The possibility of a similarity between insulin-like growth factor-I (IGF-I) and
      insulin resistance in epitrochlearis muscles of rats fed a high fat diet [20%
      (wt/wt) fat] vs. a low fat diet [5% (wt/wt) fat] was investigated. Half-maximally
      and maximally effective concentrations of IGF-I- and insulin-stimulated 3-O
      methyl-glucose transport were 2.32 and 25 nM, respectively, for IGF-I, compared
      with 0.79 and 20 nM for insulin. The high fat diet reduced both responsiveness
      and sensitivity of IGF-I-stimulated 3-O-methyl-glucose transport in parallel with
      the impaired insulin-stimulated 3-O-methyl-glucose transport. IGF-I binding at
      2.5 nM to incubated epitrochlearis muscle was also decreased by the high fat diet
      (P < 0.05). Thus, the high fat diet caused simultaneous IGF-I and insulin
      resistance in rat skeletal muscle. The IGF-I resistance induced by feeding the
      high fat diet seems at least partially due to a reduction in IGF-I binding.

PMID- 7628367
TI  - Asparagine-linked oligosaccharide structures determine clearance and organ
      distribution of pituitary and recombinant thyrotropin.
AB  - The recombinant human TSH (rhTSH) with highly sialylated oligosaccharide chains
      showed higher in vivo bioactivity and a lower MCR than the predominantly sulfated
      pituitary human TSH (phTSH). The aim of the present study was to investigate the
      role of terminal carbohydrate residues in organ distribution and metabolic
      clearance of TSH using an in vivo rat model. The different 125I-labeled TSH
      preparations with distinct carbohydrate composition were injected i.v. At various
      time points (5-180 min) after bolus TSH injection, blood, liver, kidney, spleen,
      lung, heart, and thyroid samples were collected. TSH uptake was determined by
      trichloroacetic acid precipitation of [125I]TSH in the organ homogenates. The
      rhTSH (solely sialylated) was distributed predominantly to the kidneys 5, 15, and
      30 min after injection. In contrast, phTSH (sulfated/sialylated) and bovine TSH
      (bTSH; solely sulfated) were cleared predominantly by the liver (at 5 min), with
      a later renal phase of clearance (at 30 min). Asialo-rhTSH was cleared by the
      liver with only minor involvement of other organs. The early liver uptake (at 5
      min) was proportionally highest for the asialo-rhTSH and bTSH preparations and
      lowest for rhTSH, which correlated inversely with the serum levels and the degree
      of sialylation. Blockade of the N-acetylgalactosamine (GalNAc) sulfate receptors
      by injection of bovine LH resulted in a significant decrease in liver uptake of
      phTSH. Similarly, liver uptake of asialo-rhTSH was significantly inhibited by
      injection of asialo-fetuin. Thus, phTSH and bTSH preparations containing sulfated
      oligosaccharide chains are cleared at least in part by the GalNAc sulfate
      specific receptors in the liver. In contrast, rhTSH with highly sialylated
      oligosaccharides in both subunits accumulates predominantly in the kidneys, even
      at the early phase of clearance, indicating that sialylated glycoprotein hormones
      escape from specific receptor-mediated clearance mechanisms in the liver. These
      data indicate that terminal sialic acid and GalNAc sulfate residues, each to a
      different extent, determine glycoprotein hormone distribution and thereby plasma
      level, which as we have shown previously is a major factor in determining the in
      vivo potency of TSH.

PMID- 7628368
TI  - Parathyroid hormone inhibits mitogen-activated protein kinase activation in
      osteosarcoma cells via a protein kinase A-dependent pathway.
AB  - Osteoblast-like cells, such as UMR 106 osteosarcoma cells, are known to be growth
      stimulated by growth factors such as EGF. In contrast, factors such as PTH and
      prostaglandin E2 inhibit their growth. The exact signal transduction mechanisms
      by which these latter factors act remain to be elucidated. Here we show that
      simultaneous treatment of UMR 106 cells with EGF and PTH-(1-34) resulted in a
      level of DNA synthesis intermediate between the levels of treatment with
      epidermal growth factor (EGF) and PTH alone. This correlated with the
      interference of PTH-(1-34) early in an EGF receptor-linked signal transduction
      pathway, i.e. the EGF-induced activation of p42 mitogen-activated protein (MAP)
      kinase. This effect was also found for prostaglandin E2, and could be potentiated
      by the phosphodiesterase inhibitor isobutyl-methylxanthine and mimicked by
      forskolin and 8-bromo-cAMP. There was a strict correlation between the lowest
      concentration of PTH-(1-34) required to enhance protein kinase A (PKA) activity
      and that required to inhibit MAP kinase activation, whereas saturating amounts of
      PTH-(3-34), a PTH analog unable to elevate PKA activity, had no effect.
      Lysophosphatidic acid- and 12-O-tetracanoylphorbol-13-acetate-induced MAP kinase
      activation were also inhibited by PTH-(1-34) and forskolin in these cells.
      Similar effects were seen on basic fibroblast growth factor-mediated MAP kinase
      activation in ROS 17/2.8 cells, indicating that this mechanism is a general
      feature of PTH in osteosarcoma cells. The inhibition of this mitogenic pathway
      through activation of PKA might play an important role in PTH-induced changes in
      proliferation and differentiation of osteoblasts.

PMID- 7628369
TI  - Growth hormone directly affects the function of the different lobes of the rat
      prostate.
AB  - In this study, we investigated the involvement of GH in rat prostate function.
      First, we demonstrated that specific transcripts corresponding to the GH receptor
      (4.5 kilobases) and to the GH-binding protein (1.2 kilobases) were expressed in
      the normal rat prostate, but also in all prostatic carcinoma cell lines tested
      (LNCaP, PC-3, MAT-Lu, MAT-LyLu, and Pif-1). Moreover, these transcripts were much
      more abundant in the human and rat carcinoma cells than in the normal tissue. One
      year-old dwarf rats were supplemented for 7 days with saline (group DR1) or
      highly purified rat GH (group DR2). Northern blotting and quantitation of
      prostatic messenger RNAs (mRNAs) revealed that GH increases the steady state
      levels of transcripts coding for androgen receptor (2.4-fold), type I and II 5
      alpha-reductases (2.6- and 2.2-fold), and several androgen-dependent proteins
      [prostatein C3 subunit (3.6-fold), probasin (11.0-fold), and R. W. B. (Royal
      Winnipeg Ballet) (12.5-fold)]. This suggests that GH might either potentiate the
      action of androgens on the prostate or act directly on this gland by a mechanism
      that does not depend on testicular androgens. To address this question, we
      supplemented hypophysectomized and castrated adult rats for 7 days with saline
      (group HC1), rat GH (group HC2), testosterone propionate (group HC3), or GH plus
      testosterone (group HC4), starting 3 days after castration. In this animal model,
      the abundance of C3 mRNA increased in all hormone-treated rats; the stimulation
      factors were 3.5 (group HC2), 25.5 (group HC3), and 9.5 (group HC4) compared to
      group HC1. Analysis of prostatein synthesis by Western blotting confirmed these
      results at the protein level. The same trend was observed for probasin and RWB
      mRNA levels. Probasin mRNA increased 4.5-fold in group HC2 and 12-fold in group
      HC3, but did not increase in group HC4 (both hormones combined); enhancement of
      RWB mRNA was, respectively, 5.0-, 28.0-, and 15.0-fold in groups HC2, HC3, and
      HC4. GH did not affect the abundance of androgen receptor mRNA. As described
      previously, the level of this mRNA dropped significantly in group HC3. GH alone
      did not significantly alter the level of either 5 alpha-reductase mRNA, whereas
      testosterone, alone or with GH, produced a 2-fold increase in type II 5 alpha
      reductase mRNA (groups HC3 and HC4). Type I isoenzyme mRNA reached 1.6 times the
      control level (group HC1) in groups HC3 and HC4.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7628370
TI  - Neuroendocrine regulation of adrenal gland and hypothalamus 5'deiodinase
      activity. II. Effects of splanchnicotomy and hypophysectomy.
AB  - This study analyzes the role of the autonomic nervous system, the pituitary
      gland, ACTH, dexamethasone (DEX), and thyroid hormones in the regulation of
      5'deiodinase (5'D) in the hypothalamus (HP) and adrenal gland (AG) of the rat.
      5'D activity was analyzed in rats under basal conditions (22 C) and during cold
      exposure (4 C, during 15, 30, 60, and 120 min). Several experimental groups were
      formed: intact animals (INT), unilateral (left) splanchnicotomized, sham
      splanchnicotomized, hypophysectomized (HPX), and sham hypophysectomized. Results
      in the hypothalamus were: 1) independent of the experimental group, the HP 5'D
      activity increased during the first 15-30 min of cold exposure; however, this
      increase was greater in operated animals than in INT rats; and 2) basal 5'D
      activity was increased in HPX rats and was also regulated by thyroid hormones.
      Results in the adrenal gland were: 1) INT rats exhibited a biphasic pattern of
      5'D activation during cold stress (30 and 60 min of exposure); 2) the splanchnic
      nerve exerted a tonic-stimulatory effect on basal AG 5'D activity; 3) the
      denervated gland preserved its ability to respond to cold; 4) in INT animals DEX
      but not ACTH had a stimulatory effect on basal activity; 5) the high 5'D activity
      post-HPX was reverted to basal values by T4 and DEX administration; 6) SHAM-HPX
      also was followed by a large increase in basal 5'D activity, and 7) this
      hyperresponse was abolished by acute ACTH and DEX administration. In conclusion,
      our results demonstrate that the mechanisms that participate in the regulation
      and activation of 5'D in the adrenal gland and the hypothalamus are of a
      neuroendocrine nature. Also, in both organs, but mainly in the HP, 5'D activity
      is T4-dependent. In addition to the tonic-stimulatory influence conveyed by the
      splanchnic nerve, AG 5'D activity is influenced by thyroid hormones,
      glucocorticoids, and probably extrapituitary factors whose nature is unknown yet.

PMID- 7628371
TI  - Differential expression of hepatic sterol carrier proteins in the streptozotocin
      treated diabetic rat.
AB  - Sterol carrier protein-2 (SCP2) is a 13.2-kilodalton protein that has been
      implicated in intracellular cholesterol transport, whereas a related sterol
      carrier protein, sterol carrier protein-X (SCPx; 58 kilodaltons) has been
      suggested to function also in the beta-oxidation of fatty acids. Although
      diabetes-related hyperlipidemia and altered cholesterol metabolism have been
      extensively studied, the intracellular cholesterol transport capacity during
      hyperglycemic states has not been examined. The fact that beta-oxidation is
      increased in diabetes whereas hepatic cholesterol metabolism is reduced suggests
      that differential expression of these sterol carrier proteins may accompany
      diabetic dyslipidemia. In this study, SCP2 protein levels were reduced by 60% in
      mildly hypercholesterolemic (cholesterol, > 130 and < 150 mg/dl; P < 0.01)
      diabetic rats and by 90% in severely hypercholesterolemic (cholesterol, > 150
      mg/dl; P < 0.002) diabetic animals. In contrast, hepatic SCPx protein expression
      increased (3.5-fold) after diabetes induction with streptozotocin (STZ). The
      decline in SCP2 was inversely related to serum cholesterol levels. Hepatic SCP
      messenger RNA levels examined by ribonuclease protection assay demonstrated that
      hepatic SCP messenger RNA was increased 2-fold in diabetic animals. Northern blot
      analysis indicated that both the 0.8-kilobase SCP2-specific and the 2.1-kilobase
      SCPx-specific transcripts increased after STZ injection. SCPx protein induction
      preceded the decline in SCP2 by 4-5 days. Insulin treatment reversed the increase
      in SCPx and prevented the decline in SCP2. We conclude that SCP2 and SCPx are
      differentially expressed in the STZ-diabetic rat and suggest that this change in
      SCP expression should be considered a potential contributing mechanism through
      which cholesterol metabolism may be altered in diabetes.

PMID- 7628372
TI  - In vitro folliculogenesis of rat preantral follicles.
AB  - The impact of various gonadotropic hormones on the growth and development of
      secondary follicles from primordial and primary follicles obtained by enzymatic
      dissociation of the ovaries of immature 14-day-old rats was studied in vitro. The
      substratum-adherent culture technique developed for studying folliculogenesis in
      the current study permitted direct visualization of follicular growth on a day to
      day basis by avoiding the cumbersome process of fixing and sectioning follicles
      in culture. The cultures were maintained in a serum-free modified McCoy's medium
      in a humidified atmosphere containing 5% CO2 at 37 C. Daily observation of the
      culture dishes under the phase contrast microscope revealed that the follicles
      grew and developed from primordial to primary and secondary follicular stages in
      the presence of FSH. Large antral follicles were able to secrete estradiol and
      progesterone into the medium, indicating that the follicles are not merely formed
      by cellular reorganization, but are physiologically functional competent units.
      The organized release of the oocyte with accompanying corona radiata was made
      possible in some secondary follicles with large antral structures by introducing
      LH into the culture medium. However, introduction of hCG (which has the
      biological properties of LH) into the cultures on day 1 resulted in follicular
      degeneration within 3-4 days of culture. Follicular organization was also
      disrupted when LH was introduced together with FSH into the medium on day 1 of
      culture. Primordial or primary follicles obtained from the ovaries could survive,
      but could not transform to secondary follicles in the absence of FSH. The results
      of our in vitro studies indicate, and therefore are in agreement with earlier in
      vivo studies, that FSH alone is essential for the progression of folliculogenesis
      to the preovulatory condition, and that LH is essential for the organized
      expulsion of the oocyte from a mature follicle. Our technique, described in the
      current study, for producing physiologically functional secondary follicles in
      culture not only allows progress in folliculogenesis to be monitored very
      closely, but also serves as a model for studying the various intrinsic factors
      that may be involved in the successful development of dominant mature Graafian
      follicles that can finally ovulate. It also facilitates access to the growing
      follicle along with its oocyte, which can, therefore, be used as a powerful model
      to study the effects of various test substances on follicular
      development.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7628373
TI  - Endotoxin-induced suppression of the somatotropic axis is mediated by interleukin
      1 beta and corticotropin-releasing factor in the juvenile rat.
AB  - This study extends the neuroendocrine role of central interleukin-1 beta (IL-1
      beta) during the stress of lipopolysaccharide (LPS) challenge to include
      inhibition of the somatotropic [GH-releasing hormone (GHRH)-somatostatin (SRIF)
      GH] axis in juvenile male rats and clarifies the role of CRF in the mediation of
      LPS/IL-1-induced changes in GHRH and SRIF neurosecretion. The results of the in
      vivo component of this study demonstrated that LPS treatment (2.5 mg/kg twice
      daily for 5 days) caused a significant attenuation of body weight gain for 2 days
      (2.4 +/- 1.7% vs. 10.3 +/- 1.8% BW/day in saline controls; P < 0.05) and failure
      of catch-up growth thereafter even though a small transient suppression of food
      intake returned to normal by the second of 4 days of treatment. Associated with
      the first day of growth attenuation was an acute suppression of all plasma GH
      parameters, including GH mass (area under the curve, 1.972 +/- 0.1837 vs. 6.402
      +/- 1.7 micrograms/ml.6 h for saline controls; P < 0.05), in animals receiving an
      acute bolus of LPS, which was blocked by prior microinjection of IL receptor
      antagonist protein (IRAP) into the third ventricle. In contrast, GH parameters
      associated with the second day of LPS-suppressed body weight gain were increased
      (GH mass, 9.4 +/- 2.2 vs. 3.5 +/- 0.5 micrograms/ml.4 h in saline controls; P <
      0.05). These increases were reversed after another 2 days of LPS treatment. In a
      series of in vitro experiments using medial basal hypothalamic (MBH) explants
      incubated with LPS [100 ng/ml alone or with 10(-7) M IRAP or 10(-6) M CRF
      antagonist (CRF-ANT)], GHRH release from MBH incubated with LPS was significantly
      greater than that in controls (231 +/- 79% vs. 71 +/- 34% of baseline release; P
      < 0.05), and this stimulation was antagonized by both IRAP and CRF-ANT. SRIF
      release was significantly increased by incubation with LPS (163 +/- 28% vs. 97 +/
      20% of the baseline for controls; P < 0.05) and blocked (to 88 +/- 14% of the
      baseline) by IRAP, but not by CRF-ANT. Finally, when MBH explants were incubated
      with IL-1 beta (10(-9) M), there was a significant inhibition of in vitro GHRH
      release (37.9 +/- 6.7% vs. 74.9 +/- 16.6% for controls), which was reversed by
      IRAP and CRF-ANT, and a significant stimulation of SRIF release (168.7 +/- 37.5%
      vs. 98.0 +/- 11.6% for controls), which was reversed by IRAP, but not CRF
      ANT.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7628374
TI  - Inhibition of serine/threonine protein phosphatases by secretagogues in insulin
      secreting cells.
AB  - Reversible protein phosphorylation is considered to be an important and versatile
      mechanism by which cells transduce external signals into biological responses.
      Cellular levels of protein phosphorylation are determined by the balanced actions
      of both protein kinases and protein phosphatases (PPases). Compared with protein
      kinases, however, serine/threonine PPases have received less attention. In the
      present study, the effects of known insulin secretagogues and some intracellular
      second messengers on the activities of serine/threonine PPases in insulin
      secreting RINm5F insulinoma cells were investigated. The stimulation of intact
      RINm5F cells with the insulin secretagogues L-arginine, L-glutamine, KCl, or ATP
      elicited time-dependent changes in PPase activities with an early (1 min)
      decrease in type 1-like and/or type 2A-like PPase activity that gradually
      returned to normal levels. Addition of cAMP, cGMP, or prostaglandins E2 and F1
      alpha at widely different concentrations to RINm5F cell homogenates failed to
      affect PPase activities. In contrast, addition of physiological concentrations of
      adenine nucleotides, which are known to increase upon secretory stimulation, to
      cell homogenates inhibited type 2A-like and, to a lesser extent, type 1-like,
      PPase activity (ATP > ADP > AMP > adenosine). ATP and ADP IC50 values for type 2A
      like PPase were approximately 75 and 250 microM, respectively. The inhibitory
      effect of ATP was reproduced and of comparable magnitude when purified PPases
      (types 1 and 2A) were used instead of RINm5F cell homogenates. It is concluded
      that insulin secretagogues cause time- and concentration-dependent inhibitory
      effects on RINm5F cell PPase activities, which may contribute to the increase in
      the phosphorylation state that occurs after stimulation of insulin release. Thus,
      inhibition of protein dephosphorylation may be a novel regulatory mechanism
      controlling the stimulus-secretion coupling in insulin-producing cells.

PMID- 7628375
TI  - Gonadotropin-releasing hormone-induced sensitization of calcium-dependent
      exocytosis in pituitary gonadotrophs.
AB  - Agonist-induced increases in cytoplasmic calcium concentration ([Ca2+]i) play a
      pivotal role in regulated exocytosis by promoting the fusion of secretory
      vesicles with the plasma membrane. In permeabilized and ATP-primed pituitary
      cells, increases in ambient [Ca2+]i stimulated the release of LH from
      gonadotrophs with an EC50 of 2-3 microM. In contrast, the responses of intact
      gonadotrophs to agonist stimulation by GnRH were characterized by transient
      [Ca2+]i elevations of up to 1.5 microM, followed by a plateau of 300-400 nM. The
      sensitivity of the exocytotic response of permeabilized cells to [Ca2+]i was
      significantly increased by GnRH, which reduced the EC50 for [Ca2+]i to the
      submicromolar concentration range. The stimulatory action of GnRH on LH release
      in permeabilized cells was not a consequence of intracellular Ca2+ release, but
      was associated with increased cytidine diphosphate diacylglycerol production.
      Activation of protein kinase C by phorbol esters caused a similar increase in the
      Ca2+ sensitivity of LH release from permeabilized cells, and this effect was not
      additive to that of GnRH. Furthermore, the GnRH-induced increase in the
      sensitivity of the exocytotic response to Ca2+ was attenuated by inhibitors of
      protein kinase C. These findings indicate that although elevated [Ca2+]i per se
      can promote LH release from permeabilized gonadotrophs, concomitant activation of
      protein kinase C is necessary to support exocytosis at the physiological [Ca2+]i
      levels that prevail in GnRH-stimulated intact cells. Such sensitization of the
      Ca(2+)-dependent secretory mechanism by protein kinase C may be an important step
      in the agonist-induced release of LH from pituitary gonadotrophs.

PMID- 7628376
TI  - Inhibition of osteoblastic cell proliferation and ornithine decarboxylase
      activity by ethanol.
AB  - Low bone mass and an increased prevalence of skeletal fractures are evident in
      the alcoholic population. Histomorphometric analysis of skeletal tissue from
      alcoholic patients reveals reduced osteoblast number and suppressed bone
      formation activity, with relative sparing of resorptive indexes. The decreased
      number of osteoblasts observed in alcoholic subjects results from either impaired
      proliferation or accelerated senescence. Polyamines and ornithine decarboxylase
      (ODC), the rate-limiting enzyme for polyamine synthesis, are essential for cell
      proliferation in a variety of cell types. To determine whether the consequences
      of ethanol on osteoblast number involve the modulation of polyamine biosynthesis,
      we examined the effect of ethanol on parameters of cell growth and ODC activity
      in a rat osteoblast-like osteosarcoma cell line (UMR 106-01). Ethanol markedly
      impaired DNA synthesis and cell proliferation in a dose-dependent fashion.
      Difluoromethylornithine, a specific inhibitor of ODC activity, induced a similar
      inhibition of UMR 106-01 cell proliferation, indicating the importance of the
      polyamine pathway in this osteoblastic cell line. Induction of ODC activity was
      impaired in ethanol-exposed cell cultures in a dose-dependent fashion that
      paralleled the antiproliferative effects. Finally, supplemental polyamine
      administration substantially improved DNA synthesis in ethanol-exposed UMR 106-01
      cell cultures. These data confirm a direct inhibitory effect of ethanol on
      osteoblast proliferation that may in part explain the reduced bone mass observed
      in subjects who consume excessive amounts of alcohol. These findings also suggest
      that altered polyamine metabolism may be an important mechanism responsible for
      the antiproliferative effects of ethanol on the osteoblast.

PMID- 7628377
TI  - Endotoxin induces parathyroid hormone-related protein gene expression in splenic
      stromal and smooth muscle cells, not in splenic lymphocytes.
AB  - PTH-related protein (PTHrP), the peptide that is responsible for most cases of
      hypercalcemia of malignancy, is also produced under normal circumstances by a
      variety of tissues. Its role and regulation at these sites are not well
      understood. Recently, we have shown that PTHrP is induced in the spleen during
      the host response to endotoxin (LPS) and that tumor necrosis factor (TNF) is a
      major mediator of this effect. Given the large body of in vitro evidence
      suggesting that PTHrP can be produced by lymphocytes and act in an autocrine loop
      to alter their function, studies were undertaken to determine whether lymphocytes
      were the cells responsible for PTHrP production in the spleen. Both constitutive
      and LPS-induced PTHrP messenger RNA (mRNA) levels were the same in mice lacking
      mature T cells (nude mice) and in mice lacking natural killer (NK) cells (due to
      pretreatment with antibody against NK 1.1) compared to levels in normal mice,
      suggesting that neither mature T cells nor NK cells were the splenic source of
      PTHrP. Even scid mice that lack functioning T and B cells responded to TNF with
      the induction of splenic PTHrP mRNA levels comparable to those in control mice.
      Localization of PTHrP mRNA in subfractions of rat spleens after in vivo treatment
      with LPS confirmed the results of the murine studies; PTHrP mRNA was barely
      detectable in the lymphocyte-rich single cell fraction of the spleen. In
      contrast, the stromal fraction of the spleen was enriched with PTHrP mRNA both in
      the basal state and in response to LPS. A similar pattern of distribution was
      seen for interleukin-6; LPS only increased mRNA levels of this TNF-inducible
      cytokine in the splenic stroma. In addition, mRNA for the PTH/PTHrP receptor,
      which decreased in response to LPS, colocalized with PTHrP mRNA in the stromal
      fraction of the spleen. Immunohistochemical studies identified PTHrP in two
      populations of splenic cells: 1) smooth muscle cells located in the splenic
      capsule and trabeculae and 2) a subpopulation of stromal cells located in the red
      pulp of the spleen, primarily in a subcapsular distribution. Consistent with the
      localization of PTHrP mRNA, lymphocytes in the white pulp of the spleen did not
      stain for PTHrP.

PMID- 7628378
TI  - Calcium signaling in single rat Leydig cells.
AB  - The steroidogenic activity of the Leydig cell is regulated by glycoprotein and
      peptide hormones with the potential to activate both adenylate cyclase and
      phospholipase C. Although the control of androgen production by LH is clearly
      mediated by cAMP, the extent to which Ca(2+)-mobilizing stimuli control Leydig
      cell function is less well defined. The basal level of intracellular calcium
      ([Ca2+]i) in adult rat Leydig cells was 70-160 nM and was unaffected by high K+
      or the dihydropyridine calcium channel agonist, Bay K 8644. These findings are
      consistent with the absence of voltage-sensitive calcium channels in the Leydig
      cell. In addition, no increase in [Ca2+]i was observed in cells treated with LH,
      CRF, and serotonin. However, both GnRH and endothelin-1 (ET-1) induced rapid and
      transient elevations of [Ca2+]i that were not associated with a sustained plateau
      phase and were unaffected by removal of Ca2+ from the incubation medium. The
      amplitude of the [Ca2+]i response was not altered by increasing concentrations of
      GnRH and ET-1, but the number of responsive cells increased progressively to a
      maximum of about 30% of the Leydig cell population. The calcium-mobilizing
      actions of GnRH and ET-1 were abolished by the GnRH and ETA receptor antagonists,
      [Dp-Glu1,D-Phe2,D- Trp3,6]GnRH and BQ-123, respectively. The majority of the
      cells expressed solely GnRH or ETA receptors, and about 10% expressed both
      receptors. GnRH-induced Ca2+ responses were observed almost exclusively in medium
      sized Leydig cells, whereas ET-induced responses were most frequent in large
      Leydig cells. These data demonstrate that single Leydig cells expressing GnRH and
      ETA receptors exhibit monophasic [Ca2+]i responses that are activated in an all
      or-none fashion. Such transient Ca2+ signaling may trigger short term cellular
      responses or could modulate the actions of gonadotropins acting through the cAMP
      signaling pathway.

PMID- 7628379
TI  - Cloning of a receptor for prostaglandin F2 alpha from the ovine corpus luteum.
AB  - A complementary DNA clone encoding a functional receptor for prostaglandin F2
      alpha (PGF2 alpha) has been isolated from an ovine large luteal cell
      complementary DNA library (prepared from day 10 mid-luteal phase RNA). This
      receptor, which has been designated FP, consists of 362 amino acids (M(r) =
      40,982) and is a member of the family of G protein-coupled receptors. Radioligand
      binding studies with membranes prepared from transfected COS cells demonstrated
      specific 17-[3H]phenyl-trinor-PGF2 alpha binding that was displaced by
      prostanoids in the order of 17-phenyl-trinor-PGF2 alpha > PGF2 alpha >
      fluprostenol > PGD2 > PGE2 >> 8-epi PGF2 alpha. Xenopus laevis oocytes injected
      with RNA encoding the ovine FP receptor responded to 17-phenyl-trinor-PGF2 alpha
      with increased membrane chloride conductance in calcium-free medium. Northern
      blot analysis with RNA from day 10 corpus luteum showed a major band of
      approximately 6.1 kilobases. On day 14, when luteolysis usually starts, the
      abundance of this 6.1-kilobase band was variable between individual ewes, and on
      day 16, when luteolysis is underway, the message was uniformly less abundant.
      This variability appeared to correlate with circulating progesterone. Thus, when
      the progesterone level was high (days 10 and 14 depending on whether luteolysis
      had started), the amount of FP receptor message was high, whereas when the
      progesterone level was low or falling (day 16), the amount of FP receptor message
      decreased. We have cloned an ovine FP receptor whose expression confers
      appropriate functional activity in COS cells and Xenopus oocytes. Furthermore,
      the level of messenger RNA encoding the FP receptor is high in the midluteal
      phase ovine corpus luteum and decreases during luteolysis.

PMID- 7628380
TI  - Effects of somatostatin on cultured human mesangial cells.
AB  - The present experiments were devoted to analyzing the hypothesis that
      somatostatin (SS) could modulate glomerular filtration rate by interacting with
      mesangial cells. Studies were performed in cultured human mesangial cells,
      passages 3-5. Radioligand experiments demonstrated the presence in the cells of
      two kinds of receptors, with high (dissociation constant 14 pM. Number of sites:
      426 fmol/mg) and low (dissociation constant 56 pM. Number of sites: 20, 111
      fmol/mg) affinity. SS prevented in a dose-dependent manner the reduction in
      planar cell surface area induced by 100 nM Angiotensin II (AII). This effect was
      not inhibited by the blockade of the vasorelaxing prostaglandins (indomethacin,
      10 microM), nitric oxide (L-N-methyl-arginine, 0.2 mM), adenylate cyclase (2,5'
      dideoxyadenosine, 0.1 mM), or guanylate cyclase (Methylene blue, 30 microM; LY
      83583, 10 microM), but it was potentiated by zaprinast, an inhibitor of the
      cyclic GMP (cGMP)-specific phosphodiesterase. SS also blocked the increase in
      myosin light chain phosphorylation induced by AII. SS increased cGMP synthesis by
      cultured human mesangial cells, an effect that seemed to be dependent on the
      stimulation of a particulate guanylate cyclase. Preincubation of the cells with
      pertussis toxin (0.5 microgram/ml) inhibited the effect of SS on the AII
      dependent changes in planar cell surface area, as well as the SS-dependent cGMP
      stimulation. In summary, these results demonstrate the ability of SS to relax
      cultured human mesangial cells, thus supporting a role for this peptide in the
      regulation of the glomerular filtration rate. The SS-dependent mesangial cell
      relaxation may be due to changes in the intracellular concentrations of cGMP, as
      a consequence of the activation of a particulate guanylate cyclase.

PMID- 7628381
TI  - Nature and bioactivity of gonadotropin-releasing hormone (GnRH) secreted during
      the GnRH surge.
AB  - Previous studies have demonstrated a neural action of estradiol in inducing a
      surge of GnRH in the ewe. However, although the GnRH and LH surges began
      concurrently, the GnRH surge consistently continued well beyond the surge of LH.
      Three experiments were conducted to test the hypothesis that the termination of
      the LH surge results from the secretion of a relatively inactive variant of GnRH
      during the later phases of the GnRH surge. In the first experiment, hypophyseal
      portal blood collected during an estrogen-induced LH surge was analyzed for GnRH
      immunoreactivity using two antibodies having specificity for the N- or C-terminal
      portion of the GnRH molecule. The duration, amplitude, and time course of the
      GnRH surge were found to be similar irrespective of the antisera used. In a
      second experiment, a competitive GnRH antagonist was administered at the
      beginning of the estrogen-induced GnRH/LH surge at a dose capable of blocking
      pituitary responsiveness for approximately half the duration of the GnRH surge.
      Antagonist treatment did not result in any change in the time of onset of the
      GnRH surge, but there was no increase in LH that naturally occurs coincident with
      onset of the GnRH surge. Rather, a persistent increase in LH secretion was
      observed during the latter stages of the GnRH surge, indicating that the GnRH
      molecules secreted at this time were biologically active. Finally, a sensitive
      and specific ovine pituitary cell bioassay was used to test bioactivity of GnRH
      in hypophyseal portal blood during different phases of the GnRH surge. GnRH
      bioactivity in samples collected early in the GnRH surge was greater than that
      before the onset of the GnRH surge but no greater than that collected during the
      descending limb of the surge. The results of all three experiments fail to
      support the hypothesis that the LH surge ends because of a change in the nature
      of the GnRH secreted. Rather they show that GnRH secreted throughout the surge is
      biologically active. Thus, the termination of the LH surge before that of the
      GnRH surge occurs for reasons other than lack of a bioactive GnRH signal.

PMID- 7628382
TI  - Thyrotropin receptor-specific antibodies in BALB/cJ mice with experimental
      hyperthyroxinemia show a restricted binding specificity and belong to the
      immunoglobulin G1 subclass.
AB  - Immunization with the extracellular domain of TSH receptor (TSHR) led to the
      development of hyperthyroxinemia in BALB/cJ, but not C57BL/6J, SJL/J, and B10.BR,
      mice. Earlier, human studies had shown that thyroid-stimulating antibodies are
      predominantly of the immunoglobulin G1 (IgG1) subclass with a narrow specificity
      to TSHR, and antibodies that block thyroid function could be of any subclass with
      a broader specificity. Therefore, antibody responses in susceptible (BALB/cJ) and
      resistant (SJL/J) mice were characterized. There were no significant differences
      in the titers, relative affinities, or isotypes of antibodies against the TSHR.
      BALB/cJ and SJL/J sera reacted with 2 and 7 of 26 overlapping peptides from the
      extracellular domain of the TSHR. The ability of sera from BALB/cJ and SJL/J mice
      to block TSH binding to TSHR was reversed by 1 and 6 of the reactive peptides,
      respectively. BALB/cJ mice showed predominantly an IgG1 response against the TSHR
      and peptides, whereas SJL/J mice showed varying levels of all IgG subclasses.
      Although SJL/J sera reacted with peptides to which blocking antibodies bind, they
      did not show hypothyroidism, suggesting that their sera contained a mixture of
      blocking and stimulating antibodies that negated the effects of each other. In
      contrast, some TSHR-specific antibodies in BALB/cJ probably represented
      stimulating antibodies.

PMID- 7628384
TI  - Thyroid hormones rapidly and stringently regulate the messenger RNA levels of the
      thyrotropin-releasing hormone (TRH) receptor and the TRH-degrading ectoenzyme.
AB  - The responsiveness of adenohypophyseal target cells for the hypothalamic
      neuropeptide TRH is known to change depending on the hormonal and physiological
      conditions of the organism. We describe here the effects of thyroid hormones on
      the transcript levels of the TRH receptor, the TRH-degrading ectoenzyme, and TSH
      in rat pituitary, as revealed by Northern blot analysis. After a single injection
      of T3 (30 micrograms/100 g BW), the transcript levels of the TRH receptor
      decreased transiently, reaching 35% of control values 4 h after injection, and
      returned to basal levels within 24 h. In contrast, the messenger RNA (mRNA)
      levels of the TRH-degrading ectoenzyme increased more dramatically in response to
      the same hormonal stimulus. Maximal levels (> 10 times above the control value)
      were present from 6-24 h after the injection, returning to basal values within 96
      h. For both transcripts, the observed effects changed in a dose-dependent manner,
      but the mRNA levels of the TRH-degrading ectoenzyme were more tightly regulated.
      Under the experimental conditions used, the mRNA levels of PRL and GH were not
      affected by the application of T3, and those of alpha-subunit exhibited only
      minor reductions. The TSH beta transcripts however, decreased rapidly in length
      and slowly in concentration, finally reaching almost undetectable levels 48 h
      after the injection. Subsequently, newly synthesized TSH beta mRNA, the same size
      as the transcripts from euthyroid rats, could be detected 96 h after treatment
      with T3. Upon treatment of the animals with the mild goitrogenic agent n
      propylthiouracil (200 mg/liter drinking water), a fast reduction in the
      transcript levels of the TRH-degrading ectoenzyme became evident. Within 1 day,
      mRNA levels decreased to less than 50% of control values. At this stage, no
      effects were observed on the transcript levels of either the TRH receptor or TSH
      beta. After 4 days of n-propylthiouracil treatment, the mRNA levels of the enzyme
      decreased further to 15% of control values, whereas the transcript concentrations
      of the TRH receptor and TSH beta rose by factors of 2 and 3.3, respectively. The
      extremely stringent regulation of the TRH-degrading ectoenzyme, a mirror image of
      that of the TRH receptor, strongly suggests that this enzyme represents an
      important regulatory element, controlling the stimulation of TRH target cells
      and, thus, adenohypophyseal hormone secretion.

PMID- 7628383
TI  - Protein kinase C-dependent down-regulation of basic fibroblast growth factor (FGF
      2) receptor by phorbol ester and epidermal growth factor in porcine granulosa
      cells.
AB  - The regulation of the basic fibroblast growth factor (bFGF, or FGF-2) receptor on
      porcine granulosa cells was studied. Receptor levels before and after cell
      differentiation in vivo and in vitro did not show any significant changes.
      Dibutyryl cAMP and the protein kinase A (PKA) inhibitor H-8 had no effect on bFGF
      binding. These results suggest that PKA was not involved in the receptor
      expression. Treatment of the granulosa cells with phorbol 12-myristate 13-acetate
      (PMA), a protein kinase C (PKC) activator, progressively decreased the number of
      bFGF receptors to about 20% of their initial levels after 8 h, and this effect
      occurred in a concentration- and time-dependent manner. Similarly, synthetic
      diacylglycerol also inhibited bFGF binding. The highly specific PKC inhibitor
      GF109203X completely prevented the reduction of bFGF binding by PMA and
      diacylglycerol. Kinetic analyses of the turnover of cell surface bFGF receptors
      in the presence of cycloheximide showed that PMA accelerated loss of receptors
      from the cell surface, suggesting the enhanced receptor internalization by PMA
      resulting in the receptor reduction. PMA did not influence steady-state FGF
      receptor messenger RNA levels. PMA induced an increased PKC activity in the
      membrane fraction, and among PMA sensitive PKC alpha, beta II, delta and epsilon,
      only PKC alpha was readily detected by immunoblotting and translocated to the
      membrane fraction. PMA-pretreated cells showed negligible effect on c-fos
      messenger RNA induction in response to bFGF stimulation, indicating a functional
      reduction of receptors. When cells were incubated with epidermal growth factor,
      receptor levels were reduced, but this effect was not observed in the presence of
      GF109203X. These results suggest that the bFGF receptor in porcine granulosa
      cells is regulated by the PKC, not PKA, pathway in an isoenzyme-specific fashion
      and that its possible mechanism may involve regulation of receptor
      internalization.

PMID- 7628385
TI  - Functional analysis of estrogen-responsive elements in chinook salmon
      (Oncorhynchus tschawytscha) gonadotropin II beta subunit gene.
AB  - The salmon gonadotropin II gene regulates ovulation and spawning. Analysis of the
      5' flanking sequence of the hormone-specific beta-subunit of salmon gonadotropin
      II (sGTHII beta) gene reveals the presence of several presumptive estrogen
      responsive elements (ERE). The participation of ERE in the control of sGTHII beta
      gene transcription was examined by the transient expression of sGTHII beta gene
      promoter-chloramphenicol acetyltransferase chimeric DNA constructs in HeLa cells,
      with the cotransfection of a rainbow trout estrogen receptor expression vector.
      Three ERE have been identified: the proximal ERE [pERE, at -267 base pair (bp)
      from the transcription start site], the distal ERE (dERE, at -2698 bp, three
      GGTCA motifs each separated by exactly 31 bp), and the half-ERE (1/2ERE, at -157
      bp as a GGTCA motif), respectively. The pERE (TGTCAATCTGACC) represents a novel
      but less effective variation of the consensus ERE (cERE). The dERE is a unique
      estrogen-induced enhancer. It requires the participation of the pERE to be
      functional and the enhancer activity of pERE and dERE is promoter specific. The
      contribution of 1/2ERE is minor and is not cell-type specific. The activation of
      the ERE in the sGTHII beta gene and the synergistic cooperation between the dERE
      and pERE by estradiol-17 beta is dose dependent. DNA sequences in the vicinity of
      the ERE decreases their hormone responsiveness and the synergism between dERE and
      pERE. These negative regions may contribute to the quiescent endocrine state of
      the sGTHII beta gene during the regressive phase of the reproductive cycle in
      teleost.

PMID- 7628386
TI  - Insulin-like growth factor-I regulates cell proliferation in the developing inner
      ear, activating glycosyl-phosphatidylinositol hydrolysis and Fos expression.
AB  - The role of insulin-like growth factors (IGF) was investigated during the early
      development of the inner ear. IGF-I stimulated growth of otic vesicles that were
      isolated and cultured in vitro. IGF-I induced DNA synthesis, increased cell
      number, and mitotic rate in a dose-dependent manner at concentrations between 0.1
      10 nM. IGF-II also induced growth but with a lower potency, whereas insulin had
      no effect. In the presence of IGF-I, otic vesicles developed from stage 18 to
      stage 21 in 24-h cultures, mimicking the normal mitotic pattern and morphogenesis
      in vivo. IGF-I also stimulated growth in the cochleovestibular ganglion. Binding
      of 125I-IGF-I to specific receptors occurred with high affinity. An
      autoradiographic study of sections from otic vesicles showed radiolabeled IGF-I
      in the epithelium. Immunoreactivity to IGF-I was detected in the otic vesicle and
      in the cochleovestibular ganglion. Intracellular signaling mechanisms of IGF were
      explored by studying the turnover of glycosylated phosphatidylinositols and the
      expression of Fos oncoprotein. IGF-I rapidly increased Fos levels in cultured
      otic vesicles. Furthermore, antisense oligonucleotides complementary to c-fos
      were able to inhibit IGF-I-induced growth. Both IGF-I-induced cell proliferation
      and Fos expression were blocked by an antiinositol phosphoglycan (alpha-IPG)
      antibody. This work suggests that IGF-I may be a candidate to regulate
      proliferative growth of the otic primordium during normal development and that
      this action requires the sequential modulation of glycosyl-phosphatidylinositol
      turnover and Fos expression.

PMID- 7628387
TI  - Follicle-stimulating hormone amplifies the population of differentiated
      spermatogonia in the hypophysectomized testosterone-replaced adult rhesus monkey
      (Macaca mulatta).
AB  - Although testosterone supports all phases of spermatogenesis in primates, FSH is
      obligatory for quantitatively normal spermatogenesis. To further investigate the
      mechanism of action of FSH on spermatogenesis, eight adult male rhesus macaques
      were hypophysectomized and supplemented daily with cortisone acetate (5 mg/kg BW,
      sc) and T4 (50 mg/animal, orally). Complete pituitary ablation was established by
      1) a decline in mean testicular volume to 8% of the prehypophysectomy value; 2) a
      failure to secrete gonadotropins in response to 50 micrograms GnRH, iv; and 3) an
      absence of pituitary in the sella turcica on postmortem examination. Testosterone
      filled SILASTIC brand capsules (Dow Corning) were implanted sc to restore
      testicular testosterone to normal levels. Once the testes had achieved maximum
      growth under testosterone stimulation alone, the animals were implanted with
      indwelling venous catheters. In four animals, a pulsatile infusion of human FSH
      (one pulse of 4 IU/kg BW every 3 h) was administered for 12 days, and the other
      four monkeys received vehicle. Testosterone replacement continued throughout the
      experiment. At the termination of the 12 days of FSH stimulation or vehicle
      administration, the right testes were removed. The left testes were removed 22
      days later to investigate whether testosterone was able to maintain the effects,
      if any, of FSH stimulation. Portions of each testis were fixed in Bouin's
      solution and subsequently prepared for histological examination, whereas other
      portions were frozen in liquid nitrogen for determination of testicular
      testosterone content. Five hundred cross-sections of seminiferous tubules in
      periodic acid-Schiff-hematoxylin-stained histological sections were randomly
      selected from each testis. The stage of the seminiferous epithelial cycle in
      these sections was identified, and the germ cells and Sertoli cells were counted
      in each. All cell counts were corrected by the Abercrombie method and expressed
      per cross-section of seminiferous tubule. Treatment with FSH for 12 days failed
      to influence the numbers of either Sertoli cells or Ad and Ap stem spermatogonia.
      In striking contrast, the number of all four generations of differentiated (B1,
      B2, B3, and B4) spermatogonia were significantly amplified by stimulation with
      human FSH for 12 days. As reflected by the analysis of the left testes collected
      22 days after termination of the gonadotropin treatment, the progeny of these B
      spermatogonia were not maintained in the absence of FSH. In conclusion, the
      results of the present study indicate that the action of FSH to quantitatively
      maintain spermatogenesis in the rhesus monkey is mediated by a selective
      amplification of B spermatogonia.

PMID- 7628388
TI  - Prolactin activates Ras via signaling proteins SHC, growth factor receptor bound
      2, and son of sevenless.
AB  - Identification of the signal transduction pathways used by PRL is essential for
      understanding the role of PRL receptors in growth and differentiation processes.
      Early cellular mediators of PRL receptor activation include tyrosine kinases of
      the Janus kinase (JAK) and SRC families, with rapid nuclear signaling via
      tyrosine phosphorylated signal transducers and activators of transcription. In
      the present study we provide the first demonstration of PRL-induced activation of
      Ras, an oncogenic protein that supports an alternative signaling route from the
      membrane to the nucleus. PRL stimulated Ras in rat Nb2-SP lymphoma cells, as
      detected by a 2.0-fold increase in the GTP-bound state of the molecule (P <
      0.01). This activation was associated with marked tyrosine phosphorylation and
      increased membrane association of the 52-kilodalton form of SHC. Moreover, PRL
      induced binding of SHC to growth factor receptor bound 2 and the guanine
      nucleotide exchange factor son of sevenless, a common method used by growth
      factor receptors to activate Ras. In contrast, no apparent regulation by PRL of
      Ras via VAV or p120 Ras-guanosine triphosphatase-activating protein was detected,
      based upon an absence of PRL-inducible tyrosine phosphorylation of these
      proteins. Collectively, these results provide a molecular bridge between
      activation of PRL receptor-associated tyrosine kinases and subsequent stimulation
      of the serine/threonine kinase Raf-1, an established Ras target that was recently
      shown to be activated by PRL in Nb2 cells. We conclude that PRL is able to
      activate Ras via recruitment of the signaling proteins SHC, growth factor
      receptor bound 2, and son of sevenless in Nb2 cells. Moreover, PRL induced
      tyrosine phosphorylation of SHC in two of three PRL-responsive human breast
      cancer cell lines, suggesting that SHC-mediated Ras activation is a commonly used
      signaling strategy by PRL.

PMID- 7628389
TI  - Tumor necrosis factor-alpha inhibition of 17 alpha-hydroxylase/C17-20 lyase gene
      (Cyp17) expression.
AB  - Testosterone biosynthesis in Leydig cells is dependent on the action of 17 alpha
      hydroxylase/C17-20 lyase cytochrome P450 (P450c17), which is encoded by the Cyp17
      gene. Tumor necrosis factor-alpha (TNF alpha), a proinflammatory cytokine,
      inhibits cAMP-stimulated testosterone production in mouse Leydig cells. The
      inhibition of testosterone production is parallel to the inhibition of P450c17
      messenger RNA and protein levels. To examine the mechanism of TNF alpha-mediated
      inhibition of steroidogenesis, the effect of TNF alpha on cAMP-stimulated
      induction of Cyp17 expression was investigated. To determine whether the protein
      kinase C (PKC) signaling pathway is involved in TNF alpha inhibition of
      steroidogenesis, the effects of the PKC activator, phorbol 12-myristate 13
      acetate (PMA), and the PKC inhibitor, calphostin C, were examined. Treatment of
      normal mouse Leydig cells in primary culture with 50 microM 8-bromo-cAMP (cAMP)
      plus 1 ng/ml TNF alpha or 10 nM PMA caused a similar (approximately 90%) decrease
      in testosterone accumulation and cAMP-stimulated P450c17 messenger RNA levels
      compared to those after treatment with cAMP alone. To determine whether TNF alpha
      inhibits the cAMP-induced expression of the Cyp17 gene, plasmids containing two
      different size fragments of the 5'-flanking region of the Cyp17 gene upstream of
      the chloramphenicol acetyltransferase (CAT) reporter gene were transiently
      transfected into MA-10 tumor Leydig cells, and the effect of TNF alpha on cAMP
      induced CAT activity was determined. Treatment of cells, transfected with either
      plasmid, with 500 microM cAMP plus increasing concentrations (0.1, 1.0, and 10
      ng/ml) of TNF alpha resulted in a dose-dependent repression of cAMP-stimulated
      CAT activity. Higher concentrations of TNF alpha (up to 100 ng/ml) did not result
      in greater inhibition. Treatment of transfected cells with 10 nM PMA resulted in
      a 51 +/- 6.6% inhibition of cAMP-stimulated CAT activity. Calphostin C (1 microM)
      completely reversed the inhibitory effect of TNF alpha or PMA. Calphostin C alone
      had no effect on promoter activity. TNF alpha-stimulated PKC alpha translocation
      was quantitated by Western blot. After treatment for 3 h, the distribution of
      immunoreactive PKC alpha in cytosol vs. nucleus was 55%/45%, 60%/40%, and 29%/71%
      in control, cAMP-treated, and TNF alpha-treated cells, respectively. TNF alpha
      stimulated PKC alpha translocation was further demonstrated by indirect
      immunofluorescence assay. PMA, a known activator of PKC, and TNF alpha had a
      similar inhibitory effect on P450c17 expression, testosterone production, and
      Cyp17-CAT activity.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7628391
TI  - Deficiency of pyruvate dehydrogenase activity in pancreatic islets of diabetic GK
      rats.
AB  - We investigated the role of islet pyruvate dehydrogenase (PDH) enzyme activity
      and fatty acid oxidation in the impaired insulin secretion in spontaneously
      diabetic GK rats. Blood glucose levels were elevated in 2- to 3-month-old GK rats
      (8.7 +/- 0.5 vs. 6.5 +/- 0.3 mM in control Wistar rats; P < 0.01), whereas serum
      insulin levels were comparable to those in control rats. Insulin and DNA contents
      were similar in freshly isolated islets from GK and control rats, whereas insulin
      responses to 27 mM glucose from GK islets were reduced by 52%. The effect of
      acetate or pyruvate on insulin responses evoked by succinate monomethylester
      (SAM) were compared to indirectly assess deficient generation of acetyl-coenzyme
      A from pyruvate. Acetate potentiated SAM-induced insulin secretion similarly in
      GK and control islets, whereas 10 mM pyruvate (which supplies acetyl-coenzyme A
      through PDH enzyme activity) failed to normally potentiate insulin secretion in
      GK islets (92% of SAM-induced response in GK vs. 154% in control islets). The PDH
      activity (active form) was decreased in GK islets by 35% (P < 0.001). The
      proportion of active form PDH to total PDH activity was reduced in GK islets (56%
      vs. 71% in control islets; P < 0.01). The activity of PDH kinase (which
      inactivates PDH by phosphorylation) was increased in GK islets, the rate of ATP
      dependent inactivation of PDH was -0.29 +/- 0.02 vs. -0.19 +/- 0.02/min in
      control islets (P < 0.05). Culturing GK islets for 48 h at 5.5 mM glucose failed
      to correct the impaired insulin response to glucose and the decreased PDH
      activity. Serum FFA levels and islet triglyceride contents did not differ between
      GK and control rats. Etomoxir (1.0 and 10 microM), a carnitine palmitoyl
      transferase I inhibitor, failed to enhance glucose-induced insulin release in GK
      islets. The following conclusions were reached: 1) a kinase-mediated decrease in
      PDH activity in islets of GK rats may in part account for the decreased ratio of
      oxidized to utilized glucose and impaired insulin release in these islets; and 2)
      impaired insulin release in the GK rats is not linked to an inhibitory influence
      of islet fatty acid oxidation.

PMID- 7628390
TI  - Expression of the gene encoding transcription factor cyclic adenosine 3',5'
      monophosphate (cAMP) response element-binding protein (CREB): regulation by
      follicle-stimulating hormone-induced cAMP signaling in primary rat Sertoli cells.
AB  - The somatic Sertoli cells of the testis are major targets for FSH and are
      important for the regulation of spermatogenesis. The binding of FSH to Sertoli
      cells activates the cAMP-dependent protein kinase A signaling pathway, resulting
      in phosphorylation of the cAMP response element-binding protein (CREB), which is
      required to transactivate genes containing cAMP response elements (CREs). Here we
      show that the addition of forskolin to cultured primary Sertoli cells results in
      the phosphorylation of CREB within 2-5 min. Phospho-CREB levels remain elevated
      with continued forskolin stimulation, but fall by 60% within 5 min after the
      removal of forskolin. In addition, we found that 8-bromo-cAMP induces CREB RNA
      accumulation in the Sertoli cells. Transient transfections of primary Sertoli
      cells with CREB promoter-chloramphenicol acetyltransferase reporter plasmids
      define a conserved 300-base pair region of the CREB promoter surrounding the
      transcription start site that is required for both basal and cAMP-inducible
      expression of the CREB gene. This region of the promoter contains three Sp1
      binding sites flanking the transcription initiation site and two CREs located 65
      and 85 base pairs downstream of the transcription initiation site. We show that
      the Sp1 motifs bind Sp1 in Sertoli extracts and contribute to basal promoter
      activity, and that the CREs bind CREB and are essential for cAMP induction of
      CREB gene transcription. These findings support the model of FSH- and cAMP
      mediated CREB autoregulation of its own promoter and may explain the dramatic
      stage-specific oscillations in Sertoli cells of CREB messenger RNA levels during
      the 12-day cycles of spermatogenesis in rat seminiferous tubules.

PMID- 7628392
TI  - Mitochondrial permeability transition is induced by in vivo thyroid hormone
      treatment.
AB  - Thyroid hormone treatment in vivo results in activation of mitochondrial Ca2+
      efflux and temperature-dependent enhanced swelling of Ca(2+)-loaded rat liver
      mitochondria. Thyroid hormone-induced swelling was effectively prevented in the
      presence of excess EGTA or cyclosporin A. Thyroid hormone treatment similarly
      resulted in a dramatic decrease in mitochondrial membrane potential (80%), proton
      gradient (45%), and proton motive force (69%) measured in Ca(2+)-loaded
      mitochondria. All three parameters were essentially restored to euthyroid values
      in the presence of excess EGTA or cyclosporin A. Mitochondrial energy-linked
      transhydrogenase activity measured in the presence of Ca2+ was 33% increased and
      38% decreased in hypothyroid and L-T3-treated hypothyroid rats, respectively,
      compared to that in euthyroid rats. Hence, in vivo thyroid hormone treatment may
      induce mitochondrial permeability transition mediated by the cyclosporin A
      sensitive permeability transition pore.

PMID- 7628393
TI  - Corticotropin release-inhibiting factor is preprothyrotropin-releasing hormone
      (178-199).
AB  - ACTH is the major regulator of the body's adaptive response to stress and the
      physiological stimulus for glucocorticoid secretion. In addition to the known
      negative feedback regulation of ACTH by glucocorticoids, a hypothalamic
      corticotropin release-inhibiting factor (CRIF) that inhibits ACTH synthesis and
      secretion has been postulated, but not identified. We previously reported that
      transfection of prepro-TRH complementary DNA into the mouse anterior pituitary
      tumor cell line AtT-20 results in inhibition of basal and corticotropin-releasing
      hormone (CRH)-stimulated ACTH synthesis and secretion, suggesting that one or
      more of the cryptic peptides encoded within the prepro-TRH precursor has CRIF
      activity. To narrow the choice of peptides responsible for CRIF activity, we
      first deleted specific sequences within the prepro-TRH complementary DNA and
      transfected these constructs into AtT-20 cells. Deletion of sequences encoding
      amino acids 119-229 resulted in the loss of CRIF activity. Of the peptides
      encoded within this region, prepro-TRH-(178-199), a 22-amino acid peptide,
      inhibited basal and CRH-stimulated ACTH synthesis and secretion in cultured
      primary anterior pituitary cells. As this peptide is processed from prepro-TRH in
      vivo, is found in the external zone of the median eminence, and is secreted from
      hypothalamic slices in vitro, prepro-TRH-(178-199) fulfills the criteria for a
      physiological CRIF. The significance of TRH and CRIF sharing a common precursor
      opens new areas of research in the integrated regulation of pituitary-adrenal and
      pituitary-thyroid functions.

PMID- 7628394
TI  - Wortmannin inhibits the action of insulin but not that of okadaic acid in
      skeletal muscle: comparison with fat cells.
AB  - To look for the possible involvement of phosphatidylinositol-3-kinase (PI3
      kinase) in insulin action in muscle, we have used wortmannin, described as a
      specific inhibitor of the enzyme, and compared its effect in muscle and in
      adipose cells. Both in intact mouse soleus muscle and in isolated rat adipocytes,
      wortmannin blocked insulin effect on glucose uptake, without markedly altering
      basal glucose uptake. In adipocyte, this effect results from a blockade of the
      translocation process because wortmannin inhibited the stimulatory action of
      insulin on both the Glut 4 movement from the internal compartment to the plasma
      membranes and the Rab4 departure from the microsomes. In a similar fashion, two
      other insulin effects, the activation of glycogen synthase and the stimulation of
      amino acid uptake, were blocked by wortmannin in skeletal muscle. Lipogenesis
      from acetate was also inhibited by wortmannin in adipocytes. By contrast,
      wortmannin did not affect muscle deoxglucose uptake when it was stimulated either
      by okadaic acid or by the protein kinase C activator tumor promoting agent. These
      results suggest that, in muscle and adipocyte, PI3-kinase inhibition causes a
      blockade of all insulin effects studied. By contrast, wortmannin did not affect
      the same responses elicited in muscle by okadaic acid or tumor promoting agent.

PMID- 7628395
TI  - Increase in messenger ribonucleic acid encoding the myometrial gap junction
      protein, connexin-43, requires protein synthesis and is associated with increased
      expression of the activator protein-1, c-fos.
AB  - Expression of the myometrial gap junction protein connexin-43 (Cx-43) increases
      dramatically with the onset of labor in association with an increase in the
      plasma estrogen to progesterone ratio. Moreover, we reported that the levels of
      messenger RNA (mRNA) and protein encoded by the Cx-43 gene are regulated
      positively by estrogen and negatively by progesterone in both pregnant and
      nonpregnant rats. However, although the Cx-43 gene has been reported to be
      responsive to estrogen, it does not contain a palindromic estrogen response
      element. It does, however, contain a consensus activator protein-1 (AP-1)-binding
      site that may be of significance, as estrogen has been reported to increase
      expression of the AP-1 proteins, Fos and Jun, in the uterus. Therefore, we tested
      the hypothesis that the increase in Cx-43 mRNA levels in the myometrium during
      labor and after estrogen administration is mediated indirectly through induction
      of trans-activating factors, of which Fos and Jun are putative candidates.
      Treatment of nonpregnant ovariectomized rats with cyclohexamide blocked the
      estrogen-induced increase in Cx-43 mRNA in the myometrium, suggesting that this
      action of estrogen requires newly synthesized protein. Estrogen treatment alone
      induced an increase in mRNA encoding c-fos and c-jun in nonpregnant rats, which
      preceded by 2-3 h an increase in Cx-43 mRNA. Labor was also associated with a
      coincident expression of c-fos and Cx-43 in the myometrium, although there was no
      change in c-jun mRNA levels during this period. These associative data were
      strengthened by our observation that in paradigms in which labor was induced
      prematurely by ovariectomy or blocked by treatment with progesterone, changes in
      c-fos expression were closely matched by changes in Cx-43 mRNA. These data
      support our hypothesis that estrogen (and, by extension, labor-)-induced
      increases in Cx-43 mRNA are mediated indirectly through newly synthesized trans
      activating factors. Moreover, the temporal correlation between the expression of
      c-fos and Cx-43 and the presence of AP-1 cis-acting elements within the Cx-43
      promoter suggest that c-fos may be one of these trans-activating proteins.

PMID- 7628396
TI  - Administration of tumor necrosis factor-alpha results in a decreased placental
      transfer of amino acids in the rat.
AB  - The administration of an acute tumor necrosis factor-alpha (TNF) dose (100
      micrograms/kg BW) to 20-day pregnant rats resulted in a substantial decrease in
      the fetal availability of maternally administered amino acids, as measured by the
      accumulation of alpha-amino-[1-14C]isobutyrate ([14C]AIB) and [1-14C]cycloleucine
      ([14C]CLEU), nonmetabolizable analogs of the amino acids alanine and leucine,
      respectively. Thus, TNF treatment resulted in a decreased accumulation of the
      tracers in the whole fetus as well as in fetal liver. The cytokine also caused
      important changes on the maternal liver, where it increased both [14C]AIB and
      [14C]CLEU accumulation. In skeletal muscle and heart, TNF treatment resulted in
      decreased [14C]AIB accumulation, but increased [14C]CLEU. These changes in tissue
      amino acid uptake were accompanied by changes in circulating amino acids. TNF
      treatment promoted an increase in the concentrations of both alanine and leucine
      in the maternal circulation, whereas no changes in the circulating concentrations
      of these amino acids were observed in the fetuses. The decreased fetal
      accumulation of maternally derived amino acid analogs is partially explained by a
      decrease in fetal blood flow [as measured by the accumulation of [14C]1,1,1
      trichloro-2,2- bis-(p-chlorophenyl)ethane] induced by the cytokine). It is
      suggested that the cytokine may be involved in fetal growth impairment during
      pathological states (such as tumor growth or chronic infection) by promoting a
      decreased transplacental passage of amino acids, essential compounds for both
      protein accretion and oxidation in fetal metabolism.

PMID- 7628397
TI  - Degradation of glucose-dependent insulinotropic polypeptide and truncated
      glucagon-like peptide 1 in vitro and in vivo by dipeptidyl peptidase IV.
AB  - The combined actions of glucose-dependent insulinotropic polypeptide (GIP) and
      truncated glucagon-like peptide-1 (tGLP-1) may fully account for the incretin
      effect. These hormones are released from the small intestine in response to oral
      glucose and stimulate insulin release. Recently, evidence has been provided
      demonstrating the degradation of GIP-(1-42) and GLP-1-(7-36)NH2 by the serum
      enzyme dipeptidyl peptidase IV (DPP IV) into the biologically inactive products
      GIP-(3-42) and GLP-1-(9-36)NH2. The objective of the current investigation was to
      develop a method to monitor the degradation of these hormones in vivo. Synthetic
      peptides were radiolabeled and purified by HPLC. Subsequent degradation of the
      peptides under various conditions was then monitored by further HPLC analysis.
      Incubation of [125I]GIP-(1-42) or [125I]GLP-1-(7-36)NH2 with Wistar rat serum or
      purified DPP IV resulted in the major N-terminal-truncated products [125I]GIP-(3
      42) and [125I]GLP-1-(9-36)NH2. These products were significantly reduced when the
      specific DPP IV inhibitor diprotin A was included in the incubation mixture and
      were absent when serum from DPP IV-deficient rats was used. When the labeled
      peptides were infused into rats at hormone levels within the physiological range,
      over 50% was metabolized to the truncated forms within 2 min. These products were
      absent when the tracers were infused into DPP IV-deficient animals. It is
      concluded that DPP IV may be a primary inactivating enzyme of both GIP and tGLP-1
      in vivo. As the N-terminal-truncated products of the DPP IV cleavage may not be
      distinguished from the biologically active hormone by currently employed assays,
      reports of circulating hormone levels should be reconsidered. The method
      described in this manuscript may be useful for investigating the durations of
      action of GIP and tGLP-1 in normal and pathophysiological conditions.

PMID- 7628398
TI  - Blockade of nitric oxide formation augments adrenocorticotropin released by blood
      borne interleukin-1 beta: role of vasopressin, prostaglandins, and alpha 1
      adrenergic receptors.
AB  - Blockade of nitric oxide (NO) formation with the arginine derivative L-N omega
      nitro-L-arginine-methylester (L-NAME) produces a dramatic increase in ACTH
      released by the iv injection of interleukin-1 beta (IL-1 beta). The present work
      investigated the potential role of three mechanisms in this effect: the
      activation of adrenergic receptors and/or the release of vasopressin (VP) or
      prostaglandins (PG). As previously observed, blockade of adrenergic receptors
      with prazosin and propranolol did not alter the stimulatory effect of IL-1 beta.
      We show here that this treatment did not significantly interfere with the
      potentiating influence of L-NAME 30 min after IL-1 injection, but blunted this
      effect at 60 min. Immunoneutralization of endogenous VP did not consistently
      decrease the ACTH response to IL-1 beta regardless of whether NO was present.
      Finally, as expected, blockade of PG synthesis with ibuprofen totally abolished
      IL-1 beta-induced ACTH secretion; in addition, it prevented the interaction
      between L-NAME and the pituitary response. In contrast to results obtained after
      the injection of IL-1 beta, neither the adrenergic antagonists nor ibuprofen
      significantly altered the ability of L-NAME to potentiate the stimulatory effect
      of VP. Collectively, these results indicate that the influence of NO on ACTH
      released by blood-borne IL-1 beta (an effect thought to be primarily exerted on
      nerve terminals in the median eminence) is not primarily mediated by endogenous
      VP. The inability of L-NAME to augment the stimulatory effect of the cytokine on
      ACTH secretion in the presence of ibuprofen suggests that PG play an obligatory
      role in the response of the hypothalamic-pituitary axis to systemic cytokine
      administration that cannot be compensated for by removing the restraining
      influence of NO. Finally, removal of the inhibitory effect of NO either unmasks
      the participation of adrenergic receptors in modulating the response of the
      hypothalamic-pituitary axis to IL-1 beta or stimulates catecholamine secretion,
      which, in turn, acts on CRF nerve terminals and/or synergizes with IL-1 beta
      induced CRF release.

PMID- 7628399
TI  - Effects of estrogen and progesterone on luteinizing hormone-releasing hormone
      messenger ribonucleic acid levels: consideration of temporal and neuroanatomical
      variables.
AB  - We examined temporal effects of estradiol (E2) and progesterone on cellular
      levels of LHRH messenger RNA (mRNA) in several brain regions. Female rats were
      ovariectomized and implanted with SILASTIC brand capsules of oil or E2 1 week
      later (day 0). Progesterone capsules were implanted on the morning of day 2.
      Using in situ hybridization histochemistry, we found that on day 2, E2 induced a
      complex temporal pattern of changes in LHRH mRNA levels. Levels in ovariectomized
      E2-treated animals were lower than control values in the morning, then increased
      before the LH surge and declined again as the surge waned. The magnitude of these
      changes was greatest in neurons of the rostral preoptic area/organum vasculosum
      of the lamina terminalis, but a similar pattern was detected in neurons of the
      medial preoptic area. No changes were seen in neurons of the diagonal band of
      Broca. Our finding that the effect of E2 on LHRH mRNA levels depends on the time
      of day and brain region examined largely reconciles discrepancies among previous
      studies. Progesterone triggered events that advanced the onset of and augmented
      the LH surge, but had no effect on LHRH mRNA levels. These findings support the
      hypothesis that the mechanism by which E2 induces region-specific changes in LHRH
      mRNA levels before the surge is separate from the progesterone-amplified
      mechanism that induces LHRH release.

PMID- 7628400
TI  - Reduced cell-cell communication in a spontaneous murine model of autoimmune
      thyroid disease.
AB  - MRL-lpr/lpr mice manifest a systemic lupus-like autoimmune disease. As part of
      this syndrome, the mice spontaneously develop autoimmune thyroiditis, which is
      morphologically and biochemically similar to human autoimmune thyroiditis. In
      this study we investigated whether thyroid tissue obtained from sites of chronic
      inflammation had altered gap junctional communication. Fresh tissue sections
      revealed that thyroid from the nondiseased mice (MRL-(+)/+) had connexins (Cx)
      localized to the plasma membrane at points of thyroid cell-cell contact. In
      contrast, the Cx in diseased mouse (MRL-lpr/lpr) thyroid tissue were not
      localized to the plasma membrane, and the fluorescent intensity was reduced for
      Cx43 and Cx26. Northern analysis confirmed that murine thyroid tissue expressed
      messenger RNA for these Cx. However, the diseased tissue expressed lower levels
      of Cx32 and Cx26 messenger RNA. The infiltrating cells and their biologically
      active products present in the diseased thyroid tissue may mediate the reduced Cx
      expression and aberrant gap junctional assembly. We established primary thyrocyte
      cultures to determine whether these differences persisted when the inflammatory
      factors were removed. The nondiseased thyroid cells were communication competent,
      with fluorescent dye transfer proceeding from the injected cell to primary
      contacts (95%) and to second and third order neighboring cells in 75% of the
      trials. Thyroid cells from the diseased mice were communication incompetent, in
      that 80% of microinjections failed to result in dye transfer to cells in direct
      contact. Immunocytochemistry indicated that the functional coupling in the normal
      mouse thyroid cells was associated with Cx43 located in the plasma membrane as
      assembled gap junctional plaques. The communication-deficient diseased thyroid
      cells had internalized Cx43 predominantly localized to perinuclear regions of the
      cells. Collectively, these data document altered Cx-protein distribution in the
      autoimmune diseased thyroid. The diseased thyroid tissue was devoid of plasma
      membrane identifiable gap junctions and deficient in intercellular communication.
      Culturing removed the inflammatory mediators; however, the disease cells retained
      their communication incompetence. These results suggest that if this deficiency
      was initiated by components of the inflammation process, then protracted changes
      must have occurred so that the continued presence of these factors was no longer
      required to sustain this difference.

PMID- 7628401
TI  - Prolactin is a local growth factor in rat mammary tumors.
AB  - PRL is a mitogenic hormone that shares many characteristics with growth factors.
      The recent demonstration that rat mammary tissue expresses PRL messenger RNA
      (mRNA) led us to hypothesize that PRL may act as an autocrine/paracrine growth
      factor in the mammary gland and may be a determinant in mammary carcinogenesis.
      To examine this, mammary tumors were induced in rats by injection of the
      carcinogen nitrosomethylurea (NMU). In vitro studies used a cell line derived
      from NMU-induced mammary tumors. Expression of PRL and PRL receptor was assessed
      by reverse transcriptase-polymerase chain reaction. The NMU-induced mammary
      tumors and the cell line express mRNA for both PRL and PRL receptor (the long and
      short isoforms); additional hybridizing polymerase chain reaction products were
      seen in the tumors, but not in lactating mammary tissue. Immunoreactive PRL was
      detected in the NMU-induced tumors. The effect of PRL on cell proliferation was
      assessed by culturing NMU cells with PRL antiserum. The PRL antiserum inhibited
      cell proliferation by up to 70% compared to the effect of normal rabbit serum or
      GH antiserum. In summary, we showed that NMU-induced mammary tumors express mRNA
      for PRL and PRL receptor. Addition of PRL antiserum to cultured NMU cells
      significantly inhibited their growth. We propose that PRL may be acting as a
      local growth factor that stimulates the proliferation of mammary tumors.

PMID- 7628402
TI  - Modulation of osteogenic cell ultrastructure by RS-23581, an analog of human
      parathyroid hormone (PTH)-related peptide-(1-34), and bovine PTH-(1-34).
AB  - RS-23581, a synthetic analog of human PTH-related protein-(1-34), and the amino
      terminal 34 amino acids of bovine PTH [bPTH-(1-34)] increase bone mineral
      density. We wished to determine how quickly the ultrastructure of the osteogenic
      cells, i.e. osteoblasts and lining cells, of the cancellous bone of the second
      lumbar vertebra of ovariectomized rats was altered in response to the initiation
      and cessation of treatment. Ovariectomized rats were injected daily with 80
      micrograms/kg RS-23581, bPTH-(1-34), or vehicle for 19 days. Animals were killed
      throughout the treatment period and during the ensuing 10 days. By 5 days after
      the initiation of treatment with either peptide, the cells on the trabecular
      surface were predominantly (> 90%) osteoblasts, with only a small increase in the
      total cell number. Throughout the dosing period, the relative area of the
      cytoplasm of osteogenic cells from rats treated with RS-23581 or bPTH-(1-34) was
      greater than that of cells from the ovariectomized control group, suggesting a
      relationship between bone formation and cytoplasmic mass. By 7 days after the
      cessation of treatment, the trabecular surface was covered predominantly by
      lining cells without a change in cell number. Thus, these peptides apparently
      promote the osteoblast phenotype; the osteoblasts revert to lining cells after
      the peptides are withdrawn.

PMID- 7628403
TI  - Evidence that intermittent treatment with parathyroid hormone increases bone
      formation in adult rats by activation of bone lining cells.
AB  - Previous studies demonstrated that intermittent treatment with PTH increases
      osteoblast number and bone formation in growing and adult rats. The cellular
      mechanism for this increase in osteoblast number was investigated in 16-month-old
      female rats. Continuous [3H]thymidine infusion over a 1-week intermittent PTH
      [human PTH-(1-34)] treatment period was performed to determine the percentage of
      newly formed osteoblasts that originate from progenitor cells. To verify
      increases in bone formation, we performed histomorphometry and Northern blot
      analysis of selected bone matrix proteins. PTH treatment resulted in dramatic
      increases in fluorochrome-labeled perimeter (727%), osteoid perimeter (735%),
      osteoblast number (626%), and steady state mRNA levels of osteocalcin (946%) and
      type 1 collagen (> 1000%). Autoradiographic analysis of metaphyseal sections
      revealed no difference in the percentage of [3H]thymidine-labeled osteoblasts
      between PTH- and vehicle-treated groups (4.3 +/- 1.3% vs. 5.7 +/- 2.7%,
      respectively). Similar changes were observed in PTH-treated ovariectomized rats.
      As the PTH-induced increase in osteoblast number did not require proliferation of
      progenitor cells we carried out an additional experiment in adult ovariectomized
      rats to determine the onset of PTH action. Incorporation of [3H]proline in the
      distal femoral epiphysis of PTH-treated adult ovariectomized rats was increased
      within 24 h. We conclude that the rapid PTH-induced rise in bone formation did
      not require cell proliferation and was most likely due to activation of
      preexisting bone lining cells to osteoblasts.

PMID- 7628404
TI  - Expression and steroid hormonal control of Muc-1 in the mouse uterus.
AB  - Previous studies from our laboratory established that large M(r) mucin
      glycoproteins are major apically disposed components of mouse uterine epithelial
      cells in vitro. The present studies demonstrate that Muc-1 represents one of the
      apically disposed mucin glycoproteins of mouse uterine epithelia, and that Muc-1
      protein and messenger RNA (mRNA) expression are regulated in the periimplantation
      mouse uterus by ovarian steroids. Muc-1 expression is exclusive to the epithelial
      cells of the uterus under all conditions examined. Muc-1 expression is high in
      the proestrous and estrous stages and decreases during diestrous. Both Muc-1
      protein and mRNA decline to barely detectable levels by day 4 of pregnancy, i.e.
      before the time of blastocyst attachment. In contrast, Muc-1 expression in the
      cervix and vagina is maintained during this same period. Delayed implantation was
      established in pregnant mice by ovariectomy and maintained by the administration
      of exogenous progesterone (P). Initiation of implantation was triggered by
      coinjection of P-maintained mice with a nidatory dose of 17 beta-estradiol (E2).
      Muc-1 levels in the uterine epithelia of P-maintained mice declined to low levels
      similar to those observed on day 4 of normal pregnancy. Coinjection of E2 did not
      alter Muc-1 expression, suggesting that down-regulation of Muc-1 is a P-dominated
      event. This was confirmed in ovariectomized nonpregnant mice, which displayed
      stimulation of Muc-1 expression after 6 h of E2 injection. E2-Stimulated Muc-1
      expression was inhibited by the pure antiestrogen, ICI 164,384. Although P alone
      had no effect on Muc-1 expression, it antagonized the action of E2. Injection of
      pregnant mice with the antiprogestin, RU486, a known implantation inhibitor, on
      day 3 of pregnancy restored high level expression of Muc-1 mRNA on day 4,
      indicating that down-regulation of Muc-1 is P receptor mediated. Collectively,
      these data indicate that Muc-1 expression in mouse uterine epithelium is strongly
      influenced by ovarian steroids. It is suggested that the loss of Muc-1
      contributes to generation of a receptive uterine state.

PMID- 7628405
TI  - Parathyroid hormone increases the number of tartrate-resistant acid phosphatase
      positive cells through prostaglandin E2 synthesis in adherent cell culture of
      neonatal rat bones.
AB  - Tartrate-resistant acid phosphatase (TRAP) is expressed during one of the steps
      of osteoclast differentiation. The involvement of prostaglandin E2 (PGE2)
      synthesis in PTH-induced increases in TRAP-positive cell number was studied in an
      improved slowly adhering cell culture system, prepared by removing preexisting
      osteoclasts from disaggregated bone cells obtained from 6-day-old rats. The
      majority of the TRAP-positive cells that appeared were mononuclear. In 1-day
      culture, PTH (0.025-0.25 nM) and PGE2 (1 microM) increased the number of mono-
      and multinucleated TRAP-positive cells. Indomethacin (50 microM) inhibited PTH
      induced increase, and the inhibition was significantly abolished by the addition
      of PGE2. SC-19220, a specific antagonist for one class of PGE2 receptor,
      inhibited the increase induced by PTH and PGE2. PTH significantly stimulated the
      production of PGE2 in the culture. Peroxides, which are produced as byproducts of
      PGE2 biosynthesis, were detected in the adherent cells using dichlorofluorescene
      and increased the number of TRAP-positive cells. Small resorption pits were
      recognized on the surfaces of bone slices on which slowly adhering cells had been
      incubated for 3 days with PTH. These findings showed that PTH, through its
      effects on PGE2 synthesis and the subsequent reactions, induced the step at which
      TRAP is expressed, possibly during the differentiation of osteoclasts.

PMID- 7628406
TI  - Immunization against the N-terminal peptide of the inhibin alpha 43-subunit
      (alpha N) disrupts tissue remodeling and the increase in matrix metalloproteinase
      2 during ovulation.
AB  - Immunization of ewes against the N-terminal peptide of inhibin alpha 43 (alpha N)
      reduces fertility; this is thought to be due to impaired oocyte release at
      ovulation. This study further investigates the effect of alpha N
      immunoneutralization on the ovulatory process. Light microscopy was used to
      examine the effects of alpha N immunization of the tissue-remodeling process
      during ovulation and formation of the corpus luteum (CL) structure. Changes in
      follicular levels of matrix metalloproteinase-2 (MMP-2) with approaching
      ovulation were also investigated in normal and alpha N-immunized ewes.
      Differences in structure of 2-day-old CL were observed between control and alpha
      N-immunized ewes. Control CL had confluent luteal tissue throughout the internal
      structure and invaginations of theca and vasculature were common and penetrated
      deep into the luteal tissue. Immunized ewe CL had large fluid-filled antra,
      giving them a cystic appearance; luteal tissue remained a thin 10- to 15-cell
      layer lining the wall surrounding the antrum. Infolding of the surrounding tissue
      was incomplete, and thecal/vascular invaginations were rare and failed to
      penetrate into the luteal tissue. Morphologically normal rupture stigma were seen
      at the apex of both control and alpha N-immunized CL. Gelatin-digesting activity
      in follicular fluid collected 0, 12, and 24 h after hCG administration in control
      ewes increased significantly as the time of ovulation approached (827 +/- 182,
      842 +/- 159, and 1230 +/- 89 mU/ml, respectively, in Exp 1; 743 +/- 32, 1182 +/-
      98, and 1306 +/- 91 mU/ml at the same times in Exp 2). alpha N immunization
      reduced follicular gelatinase activity at each time in Exp 1 (533 +/- 132, 740 +/
      67, and 809 +/- 147 mU/ml) and Exp 2 (587 +/- 21, 768 +/- 27, and 891 +/- 53
      mU/ml); the reduction was significant at 24 h in Exp 1 and at all times in Exp 2.
      Gelatin zymography of follicular fluid revealed bands of gelatinase of 72/67
      kilodaltons, consistent with latent and active MMP-2. The area digested by both
      latent and active MMP-2 increased with approaching time of ovulation and was
      reduced by alpha N immunization. These data suggest that MMP-2 has a role in the
      tissue-remodeling processes of ovulation and CL formation in the ewe and that
      immunization against alpha N, which impairs fertility, effects the preovulatory
      cascade of intrafollicular proteolytic activity, reducing MMP-2 levels and
      disrupting normal CL formation.

PMID- 7628407
TI  - Ablation of bcl-2 gene expression decreases the numbers of oocytes and primordial
      follicles established in the post-natal female mouse gonad.
AB  - Oocyte loss, either directly through attrition (germ cell death) or indirectly
      through follicular atresia (somatic or granulosa cell death), is a fundamental
      event associated with defining the time of normal or premature reproductive
      senescence in females. Although apoptosis has been reported to function as the
      underlying mechanism responsible for death of both germ cells and somatic cells
      in the ovary, the final molecular steps which commit ovarian cells to death have
      not been fully elucidated. To examine if death repressor activity of the bcl-2
      gene product is important for germ cell survival, we conducted studies using a
      Bcl-2 loss-of-function (bcl-2 -/-) transgenic mouse model. Histological analyses
      revealed that ovaries collected from bcl-2 -/- mice possessed numerous aberrantly
      formed primordial follicle-like structures containing a single layer of granulosa
      cells without an oocyte. Additionally, the total number of primordial follicles
      present which contained a healthy oocyte was markedly reduced in bcl-2 -/- mice
      as compared to heterozygote (bcl-2 -/+) or wild-type (bcl-2 +/+) mice, suggesting
      that expression of the bcl-2 death repressor gene is critical for endowment of a
      normal complement of germ cells and primordial follicles in the mammalian ovary.

PMID- 7628408
TI  - Interleukin-15: a novel anabolic cytokine for skeletal muscle.
AB  - Interleukin-15 (IL-15) is a recently discovered growth factor which is highly
      expressed in skeletal muscle. In order to determine a functional role for IL-15
      in skeletal myogenesis, the effects of IL-15 on myoblast proliferation and muscle
      specific myosin heavy chain (MHC) expression were analyzed using the mouse C2
      skeletal myogenic cell line and primary fetal bovine skeletal myogenic cultures.
      IL-15 had no effect on [3H]thymidine incorporation, nor on the rate of myoblast
      differentiation, assessed by anti-MHC immunocytochemical staining, in either type
      of culture. However, Western blot analyses revealed that IL-15 used at
      concentrations of 10 or 100 ng/ml increased MHC accumulation five-fold in C2
      myoblast cultures and 2.5-fold in primary bovine myogenic cultures. Moreover, C2
      myotubes formed in the presence of IL-15 appeared larger than controls. These
      findings indicate IL-15 can stimulate differentiated myocytes and muscle fibers
      to accumulate increased amounts of contractile proteins. Well-fused primary
      bovine myogenic cultures treated with the mitotic inhibitor aphidicolin, then
      administered IL-15 and/or the anabolic growth factor insulin-like growth factor-I
      (IGF-I), were analyzed for MHC accumulation using Western blots. IL-15 used at 10
      ng/ml doubled MHC accumulation and was as effective as IGF-I used at 10 or 100
      ng/ml. IL-15 and IGF-I used together increased MHC accumulation close to five
      fold, indicating these two factors can act additively on muscle fibers. These
      findings indicate IL-15 affects parameters associated with skeletal muscle fiber
      hypertrophy, and suggest that IL-15 may be a novel anabolic agent to increase
      skeletal muscle mass.

PMID- 7628409
TI  - Increased GnRH mRNA in the GnRH neurons expressing cFos during the proestrous LH
      surge.
AB  - GnRH neuronal activity is increased during the proestrous LH surge as assessed by
      the expression of cFos. Whether there is an increase in GnRH mRNA concomitant
      with GnRH neuronal activation is still controversial. In the present study we
      have compared GnRH mRNA levels in GnRH neurons expressing cFos (activated) with
      those not expressing cFos during the proestrous LH surge. Brain tissue was
      obtained from adult female rats perfused on proestrus before (1100-1300 hr) or
      during (1500-1900 hr) the LH surge. Twenty-five microns free-floating brain
      sections were subjected to double labeling of cFos by immunocytochemistry and of
      GnRH mRNA by in situ hybridization using an 35S-labeled cRNA probe. Another
      series of sections were stained by double-label immunocytochemistry for cFos and
      GnRH. Serum LH concentrations and cFos expression in GnRH neurons indicated that
      rats sacrificed at or before 1300 hr had basal levels of LH secretion, and no
      cFos activity was detected in GnRH neurons. In animals sacrificed between 1500
      and 1900 hr, LH concentrations were at levels indicative of the ascending phase
      of the LH surge. A significant positive correlation between plasma LH values and
      the proportion of GnRH mRNA-containing neurons expressing cFos was observed. The
      average cellular GnRH mRNA content (silver grain numbers per cell) during the LH
      surge was not different from that before the surge. However, if GnRH neurons
      during the surge were further divided into cFos-positive and cFos-negative
      neurons, GnRH mRNA levels in the cFos-positive GnRH neurons were significantly
      increased by 28% when compared with GnRH neurons without cFos expression. These
      data suggest that cFos expression in GnRH neurons during the proestrous LH surge
      identifies transcriptionally more active GnRH neurons.

PMID- 7628411
TI  - Not your average Joe.

PMID- 7628410
TI  - Protection against procarbazine-induced testicular damage by GnRH-agonist and
      antiandrogen treatment in the rat.
AB  - Suppression of spermatogenesis in LBNF1 rats by treatment with the GnRH agonist
      Zoladex combined with the antiandrogen flutamide was evaluated in order to
      rapidly achieve protection of spermatogenic stem cells against procarbazine with
      clinically used drugs. Zoladex-flutamide treatment required 3 weeks to suppress
      the completion of spermatogenesis; only a small degree of suppression was
      observed with Zoladex alone. The suppression of spermatogenesis was reversible.
      In rats pretreated for 3 weeks with Zoladex-flutamide, the recovery of
      spermatogenesis at 9 weeks after a single injection of procarbazine as measured
      by testis weight, testicular sperm head counts, or a histological end point was
      significantly better than without hormonal pretreatment. Thus Zoladex-flutamide
      treatment enhanced the recovery of spermatogenesis from stem spermatogonia after
      procarbazine treatment in the rat and might be applicable to protect
      spermatogenesis in patients undergoing chemotherapy for cancer.

PMID- 7628412
TI  - Estrogenicity of environmental PCBs.

PMID- 7628413
TI  - Arsenic risk assessment.

PMID- 7628414
TI  - EMFs and Alzheimer's.

PMID- 7628415
TI  - Flexing some mussel.

PMID- 7628416
TI  - Turning over a new leaf.

PMID- 7628417
TI  - Cyber-schnoz.

PMID- 7628418
TI  - Age-old genetic questions.

PMID- 7628419
TI  - Middle East Agricultural Health Study.

PMID- 7628420
TI  - Environmental justice: partnerships for communication.

PMID- 7628421
TI  - Environment & economics. Partners in progress.

PMID- 7628423
TI  - Finding a home for environmental health.

PMID- 7628422
TI  - What's in the water: the disinfectant dilemma.

PMID- 7628424
TI  - Promising polymers.

PMID- 7628425
TI  - Use of a multistrain assay could improve the NTP carcinogenesis bioassay.
AB  - There are often large strain differences in the response of laboratory animals to
      toxic chemicals and carcinogens, with some strains being totally resistant to
      dose levels that cause acute toxicity and/or cancer in other strains. The current
      National Toxicology Program carcinogenesis bioassay (NTP-CB) uses only a single
      isogenic strain of mice and rats and may therefore miss some carcinogens. New
      short-term tests to predict mutagenesis and possible carcinogenesis are validated
      using data from the NTP-CB. If the animal data are inaccurate, it may hinder this
      validation. The accuracy of the NTP-CB could be improved by using two or more
      strains of each species without increasing the total number of animals. It would
      be possible to continue to use sample sizes of 48-50 animals, but subdivide these
      into groups of 12 animals of 4 different strains (48 animals total) per dose/sex
      group, for example, instead of 48 identical animals. This would quadruple the
      number of genotypes without any substantial increase in cost. Such a multistrain
      "factorial" design would, on average, be statistically more powerful then the
      present design and should increase the chance of detecting carcinogens that
      currently may give equivocal results or go undetected because the test animal
      strains happen to be specifically resistant. When strains differ in response,
      studies of differences in metabolism, pharmacokinetics, DNA damage/repair,
      cellular responses, and in some cases identification of genetic loci governing
      sensitivity may provide biological information on toxic mechanisms that would
      help in assessing human risk and setting permissible exposure limits. The NTP may
      have made the world a safer place for F344 rats and B6C3F1 mice.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7628426
TI  - Neurogenic switching: a hypothesis for a mechanism for shifting the site of
      inflammation in allergy and chemical sensitivity.
AB  - Neurogenic switching is proposed as a hypothesis for a mechanism by which a
      stimulus at one site can lead to inflammation at a distant site. Neurogenic
      inflammation occurs when substance P and other neuropeptides released from
      sensory neurons produce an inflammatory response, whereas immunogenic
      inflammation results from the binding of antigen to antibody or leukocyte
      receptors. There is a crossover mechanism between these two forms of
      inflammation. Neurogenic switching is proposed to result when a sensory impulse
      from a site of activation is rerouted via the central nervous system to a distant
      location to produce neurogenic inflammation at the second location. Neurogenic
      switching is a possible explanation for systemic anaphylaxis, in which
      inoculation of the skin or gut with antigen produces systemic symptoms involving
      the respiratory and circulatory systems, and an experimental model of anaphylaxis
      is consistent with this hypothesis. Food-allergy-iducing asthma, urticaria,
      arthritis, and fibromyalgia are other possible examples of neurogenic switching.
      Neurogenic switching provides a mechanism to explain how allergens, infectious
      agents, irritants, and possibly emotional stress can exacerbate conditions such
      as migraine, asthma, and arthritis. Because neurogenic inflammation is known to
      be triggered by chemical exposures, it may play a role in the sick building
      syndrome and the multiple chemical sensitivity syndrome. Thus neurogenic
      switching would explain how the respiratory irritants lead to symptoms at other
      sites in these disorders.

PMID- 7628427
TI  - Design issues in studies of radon and lung cancer: implications of the joint
      effect of smoking and radon.
AB  - Many case-control studies have been undertaken to assess whether and to what
      extent residential radon exposure is a risk factor for lung cancer. Nearly all
      these studies have been conducted in populations including smokers and
      nonsmokers. In this paper, we show that, depending on the nature of the joint
      effect of radon and tobacco on lung cancer risk, it may be very difficult to
      detect a main effect due to radon in mixed smoking and nonsmoking populations. If
      the joint effect is closer to additive than multiplicative, the most cost
      effective way to achieve adequate statistical power may be to conduct a study
      among never-smokers. Because the underlying joint effect is unknown, and because
      many studies have been carried out among mixed smoker and nonsmoker populations,
      it would be desirable to conduct some studies with adequate power among never
      smokers only.

PMID- 7628428
TI  - Social and environmental factors in lung cancer mortality in post-war Poland.
AB  - Poland and other Eastern European countries have undergone heavy industrial
      development with marked increases in air pollution and occupational exposure in
      the nearly 50 years since World War II. These countries have also experienced
      substantial increases in chronic disease mortality in the past three decades.
      While it is tempting to assume a direct association between these phenomena, more
      detailed analyses are called for. Poland offers a potentially rich opportunity
      for comparing geographical patterns of disease incidence and of industrial
      change. In this paper we 1) elucidate the prospects for attributing lung cancer
      mortality to industrial emissions in Poland, using an ecological approach based
      on the hitherto unaddressed geographic differences, and accounting for regional
      differences in cigarette consumption; 2) propose explanatory hypotheses for the
      observed geographic heterogeneity of lung cancer; 3) begin systematic testing of
      the widely accepted but not well-scrutinized notion that pollution in Poland is a
      major contributor to declining life expectancy. Regions with the highest fraction
      of cancer that cannot be explained by smoking appear to be highly urbanized, have
      high population exposure to occupational carcinogens, experience the highest
      rates of alcoholism and crime, and are associated with the post- World War II
      population resettlement. Although the analysis does not rule out pollution as a
      significant contributor to lung cancer mortality, it indicates that other factors
      such as occupational exposures and various social factors are of at least
      comparable importance.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7628430
TI  - Andre Lwoff (1902-1994): remembrances.

PMID- 7628429
TI  - Validation of K-XRF bone lead measurement in young adults.
AB  - K-X-ray fluorescence (K-XRF) is a useful tool for assessing environmental
      exposure to lead in occupationally exposed individuals and older adults. This
      study explores the possibility of using this technique on young adults with low
      environmental lead exposure. Twenty-three college students, aged 18-21 years,
      were recruited for 2 hr of bone lead measurement. Bone lead measurements were
      taken from the mid-shaft tibia for periods of 30 or 60 min. In the analysis, 30
      min measurements were combined so that each subject had the equivalent of two 60
      min measurements. The average concentration of two bone lead measurements in this
      population ranged from -1.5 to 8.2 micrograms Pb/g bone mineral, with a mean of
      3.0 micrograms Pb/g bone mineral. In a one sample t-test, this mean was
      significantly different from 0 (p < 0.0001). A linear trend with age was detected
      despite the small age range of our population. By doubling the sampling time, the
      reported measurement uncertainty decreased by a factor of 1.5, resulting in
      uncertainty estimates below the mean bone lead estimates. Power calculations
      using the observed variance estimates suggest that with 80% power, differences in
      bone lead concentration of 2-3 micrograms Pb/g bone mineral can be identified in
      groups of 100 or smaller. Due to the large within-person variation in young
      adults, K-XRF may not yet be a useful diagnostic tool for individual subjects,
      but it may be of great use to environmental scientists trying to characterize
      long-term lead exposure and dose in the general population or specific
      subpopulations.

PMID- 7628431
TI  - Crystal structure of the superantigen staphylococcal enterotoxin type A.
AB  - Staphylococcal enterotoxins are prototype superantigens characterized by their
      ability to bind to major histocompatibility complex (MHC) class II molecules and
      subsequently activate a large fraction of T-lymphocytes. The crystal structure of
      staphylococcal enterotoxin type A (SEA), a 27 kDa monomeric protein, was
      determined to 1.9 A resolution with an R-factor of 19.9% by multiple isomorphous
      replacement. SEA is a two domain protein composed of a beta-barrel and a beta
      grasp motif demonstrating the same general structure as staphylococcal
      enterotoxins SEB and TSST-1. Unique for SEA, however, is a Zn2+ coordination site
      involved in MHC class II binding. Four amino acids including Ser1, His187, His225
      and Asp227 were found to be involved in direct coordination of the metal ion. SEA
      is the first Zn2+ binding enterotoxin that has been structurally determined.

PMID- 7628432
TI  - Branch migration of three-strand recombination intermediates by RecG, a possible
      pathway for securing exchanges initiated by 3'-tailed duplex DNA.
AB  - RecG protein is required for normal levels of recombination and DNA repair in
      Escherichia coli. This 76 kDa polypeptide is a junction-specific DNA helicase
      that acts post-synaptically to drive branch migration of Holliday junction
      intermediates made by RecA during the strand exchange stage of recombination. To
      gain further insight into the role of RecG, we studied its activity on three
      strand intermediates formed by RecA between circular single-stranded and linear
      duplex DNAs. Once RecA is removed, RecG drives branch migration of these
      intermediates by a junction-targeted activity that depends on hydrolysis of ATP.
      RuvAB has a similar activity. However, when RecG is added to a RecA strand
      exchange reaction it severely reduces the accumulation of joint molecule
      intermediates by driving branch migration of junctions in the reverse direction
      to that catalysed by RecA strand exchange. In comparison, RuvAB has little effect
      on the reaction. We discuss how reverse branch migration by RecG, which acts
      counter of the 5'-->3' polarity of RecA binding and strand exchange, could serve
      to promote or abort the early stages of recombination, depending on the
      orientation of the single DNA strand initiating the exchange relative to the
      adjacent duplex region.

PMID- 7628433
TI  - Vimentin-associated mitotic vesicles interact with chromosomes in a lamin B- and
      phosphorylation-dependent manner.
AB  - We have assessed the involvement of the nuclear lamins in nuclear envelope
      reassembly. Analysis of perforated mitotic cells shows that A-type lamins are
      partly cytosolic and partly chromosome-bound, whereas B-type lamins are
      associated with vesicular structures throughout cell division. Lamin B-containing
      vesicles appear to dock on vimentin intermediate filaments during prometaphase,
      but dissociate from the cytoskeleton and assemble around chromatin at later
      phases of mitosis. Mitotic vesicles isolated from prometaphase cells en bloc with
      vimentin filaments can specifically capture chromosomes. Efficient chromosome
      capturing requires cytosolic factors and a dephosphorylating environment. Urea
      stripping of the vesicles abolishes binding to chromosomes. However,
      reconstitution of the stripped membranes with purified B-type lamins restores
      their ability to bind to chromosomes in a cytosol- and dephosphorylation
      dependent fashion. Vesicles reconstituted with B-type lamins form membraneous
      'crescents' on the surfaces of chromosomes, but, unlike native vesicles, do not
      fuse into large sheets. From these observations we conclude that the initial
      targeting of mitotic vesicles to chromosomes is dependent on B-type lamins and on
      factors present in the mitotic cytoplasm. Apparently, further recruitment of
      membranes and fusion of chromosome-bound vesicles onto chromatin involves non
      lamin peripheral membrane proteins.

PMID- 7628434
TI  - A novel protein kinase gene ssp1+ is required for alteration of growth polarity
      and actin localization in fission yeast.
AB  - Temperature-sensitive suppressor mutants were isolated from two fission yeast
      mutants defective in cell shape control: ppe1, encoding a type 2A-like protein
      phosphatase, and sts5, one of 11 staurosporine-supersensitive mutants.
      Complementation tests showed that suppression was due to two chromosomal loci,
      ssp1 and ssp2. Cells of the ssp1 mutant grown at the restrictive temperature
      arrested uniformly with an elongated cell body and a 2C content of DNA.
      Interestingly, these mutant cells grew only in a monopolar manner. At a specific
      point in the G2 phase of the cell cycle, wild-type cells exhibit a drastic
      alteration in growth polarity, from mono- to bipolar. This change coincides with
      the distribution of cortical actin from one end of the cell to both ends. In the
      ssp1 mutant cells, cortical actin was localized only at one end, suggesting that
      the mutant fails to change growth polarity. Nucleotide sequence determination
      showed that ssp1+ encodes a novel protein kinase. Ectopic overexpression of ssp1+
      resulted in an altered cell morphology and cortical actin was randomly dispersed
      within the cells. Immunocytological analysis revealed that the protein was
      primarily localized in the cytoplasm and that half of the protein existed in an
      insoluble fraction. These results show that the dynamics of actin-based growth
      polarity during the cell cycle are regulated, at least in part, by a novel set of
      protein kinases and phosphatases.

PMID- 7628435
TI  - A human phosphatidylinositol 3-kinase complex related to the yeast Vps34p-Vps15p
      protein sorting system.
AB  - Phosphoinositide (PI) 3-kinases have been characterized as enzymes involved in
      receptor signal transduction in mammalian cells and in a complex which mediates
      protein trafficking in yeast. PI 3-kinases linked to receptors with intrinsic or
      associated tyrosine kinase activity are heterodimeric proteins, consisting of p85
      adaptor and p110 catalytic subunits, which can generate the 3-phosphorylated
      forms of phosphatidylinositol (PtdIns), PtdIns4P and PtdIns(4,5)P2 as potential
      second messengers. Yeast Vps34p kinase, however, has a substrate specificity
      restricted to PtdIns and is a PtdIns 3-kinase. Here the molecular
      characterization of a new human PtdIns 3-kinase with extensive sequence homology
      to Vps34p is described. PtdIns 3-kinase does not associate with p85 and
      phosphorylates PtdIns, but not PtdIns4P or PtdIns(4,5)P2. In vivo PtdIns 3-kinase
      is in a complex with a cellular protein of 150 kDa, as detected by
      immunoprecipitation from human cells. Protein sequence analysis and cDNA cloning
      show that this 150 kDa protein is highly homologous to Vps15p, a 160 kDa protein
      serine/threonine kinase associated with yeast Vps34p. These results suggest that
      the major components of the yeast Vps intracellular trafficking complex are
      conserved in humans.

PMID- 7628436
TI  - A human virus protein, poliovirus protein 2BC, induces membrane proliferation and
      blocks the exocytic pathway in the yeast Saccharomyces cerevisiae.
AB  - Inducible synthesis of poliovirus protein 2BC in Saccharomyces cerevisiae arrests
      cell growth in the G2 phase of the cell cycle, while no effects are observed upon
      expression of poliovirus genes 2B or 2C, either individually or in combination.
      Expression of 2BC induces a number of morphological modifications in yeast cells,
      one of the most striking being the proliferation of small membranous vesicles
      that fill most of the cytoplasm. These vesicles are morphologically similar to
      the cytopathic vacuoles that proliferate during the infection of human cells by
      poliovirus. The transport and processing of several yeast proteins, including
      vacuolar carboxypeptidase Y, aminopeptidase I or yeast alpha-mating factor, is
      hampered upon expression of poliovirus 2BC, suggesting that transport of proteins
      through the Golgi apparatus is impaired by this viral protein. Finally, a number
      of 2BC variants were generated and the effects of their expression on yeast
      growth, cellular morphology and protein processing were analyzed. 2BC variants
      defective in the NTPase activity were still able to interfere with yeast growth
      and the exocytic system, while deletion of 30 amino acids at the N-terminus of
      2BC impairs its function. These findings lend support to the idea that 2BC, but
      not 2B or 2C, is the protein responsible for vesicle proliferation in poliovirus
      infected cells. In addition, the activity of a human virus protein in yeast cells
      opens new avenues to investigate the exact location at which poliovirus 2BC
      interferes with the vesicular system and to test the action of other animal virus
      proteins potentially involved in modifying the vesicular system in mammalian
      cells.

PMID- 7628437
TI  - A novel periplasmic carrier protein involved in the sorting and transport of
      Escherichia coli lipoproteins destined for the outer membrane.
AB  - Lipoproteins are localized in the outer or inner membrane of Escherichia coli,
      depending on the species of amino acid located next to the N-terminal fatty
      acylated Cys. The major outer membrane lipoprotein (Lpp) expressed in
      spheroplasts was, however, retained in the inner membrane as a mature form. A
      novel protein that is essential for the release of Lpp from the inner membrane
      was discovered in the periplasm and purified. The partial amino acid sequence of
      this 20 kDa protein (p20) was determined and used to clone a gene for p20.
      Sequencing of the gene revealed that p20 is synthesized as a precursor with a
      signal sequence. p20 formed a soluble complex only with outer membrane-directed
      lipoproteins such as Lpp, indicating that p20 plays a critical role in the
      sorting of lipoproteins. Lpp released from the inner membrane in the presence of
      p20 was specifically assembled into the outer membrane in vitro. These results
      indicate that p20 is a periplasmic carrier protein involved in the translocation
      of lipoproteins from the inner to the outer membrane.

PMID- 7628438
TI  - The Drosophila insulin receptor homolog: a gene essential for embryonic
      development encodes two receptor isoforms with different signaling potential.
AB  - We report the cloning and primary structure of the Drosophila insulin receptor
      gene (inr), functional expression of the predicted polypeptide, and the isolation
      of mutations in the inr locus. Our data indicate that the structure and
      processing of the Drosophila insulin proreceptor are somewhat different from
      those of the mammalian insulin and IGF 1 receptor precursors. The INR proreceptor
      (M(r) 280 kDa) is processed proteolytically to generate an insulin-binding alpha
      subunit (M(r) 120 kDa) and a beta subunit (M(r) 170 kDa) with protein tyrosine
      kinase domain. The INR beta 170 subunit contains a novel domain at the
      carboxyterminal side of the tyrosine kinase, in the form of a 60 kDa extension
      which contains multiple potential tyrosine autophosphorylation sites. This 60 kDa
      C-terminal domain undergoes cell-specific proteolytic cleavage which leads to the
      generation of a total of four polypeptides (alpha 120, beta 170, beta 90 and a
      free 60 kDa C-terminus) from the inr gene. These subunits assemble into mature
      INR receptors with the structures alpha 2(beta 170)2 or alpha 2(beta 90)2.
      Mammalian insulin stimulates tyrosine phosphorylation of both types of beta
      subunits, which in turn allows the beta 170, but not the beta 90 subunit, to bind
      directly to p85 SH2 domains of PI-3 kinase. It is likely that the two different
      isoforms of INR have different signaling potentials. Finally, we show that loss
      of function mutations in the inr gene, induced by either a P-element insertion
      occurring within the predicted ORF, or by ethylmethane sulfonate treatment,
      render pleiotropic recessive phenotypes that lead to embryonic lethality. The
      activity of inr appears to be required in the embryonic epidermis and nervous
      system among others, since development of the cuticle, as well as the peripheral
      and central nervous systems are affected by inr mutations.

PMID- 7628439
TI  - Reconstitution of interactions between tyrosine kinases and the high affinity IgE
      receptor which are controlled by receptor clustering.
AB  - High affinity IgE receptor (Fc epsilon RI) signaling after contact with antigen
      occurs in response to receptor clustering. This paper describes methodology,
      based on vaccinia virus driven protein expression, for probing signaling pathways
      and its application to Fc epsilon RI interactions with the lyn and syk tyrosine
      kinases. Reconstitution of the complete tetrameric Fc epsilon RI receptor, lyn
      and syk in a non-hematopoietic 'null' cell line is sufficient to reconstruct
      clustering-controlled receptor tyrosine phosphorylation and activation of syk,
      without apparent requirement for hematopoietic specific phosphatases. The src
      family kinase lyn phosphorylates Fc epsilon RI in response to receptor
      clustering, resulting in syk binding to the phosphorylated Fc epsilon RI. Lyn
      also participates in the tyrosine phosphorylation and activation of syk in a
      manner which is dependent on phosphorylated Fc epsilon RI. Using overexpression
      of active and dominant negative syk proteins in a mast cell line which naturally
      expresses Fc epsilon RI, we corroborate syk's role downstream of receptor
      phosphorylation, and demonstrate that syk SH2 domains protect receptor ITAMs from
      ongoing dephosphorylation. Based on these results, we propose that receptor
      clustering controls lyn-mediated Fc epsilon RI tyrosine phosphorylation by
      shifting a balance between phosphorylation and dephosphorylation towards
      accumulation of tyrosine phosphorylated Fc epsilon RI. Fc epsilon RI tyrosine
      phosphorylation functions to bring syk into a microenvironment where it becomes
      tyrosine phosphorylated and activated, thereby allowing clustering to indirectly
      control syk activity.

PMID- 7628440
TI  - Detailed analysis of the IL-5-IL-5R alpha interaction: characterization of
      crucial residues on the ligand and the receptor.
AB  - The receptor for interleukin-5 (IL-5) is composed of two different subunits. The
      IL-5 receptor alpha (IL-5R alpha) is required for ligand-specific binding while
      association with the beta-chain results in increased binding affinity. Murine IL
      5 (mIL-5) has similar activity on human and murine cells, whereas human IL-5 (hIL
      5) has marginal activity on murine cells. We found that the combined substitution
      of K84 and N108 on hIL-5 by their respective murine counterpart yields a molecule
      which is as potent as mIL-5 for growth stimulation of a murine cell line. Since
      the unidirectional species specificity is due only to the interaction with the IL
      5R alpha subunit, we have used chimeric IL-5R alpha molecules to define regions
      of hIL-5R alpha involved in species-specific hIL-5 ligand binding. We found that
      this property is largely determined by the NH2-terminal module of hIL-5R alpha,
      and detailed analysis defined D56 and to a lesser extent E58 as important for
      binding. Moreover, two additional residues, D55 and Y57, were identified by
      alanine scanning mutagenesis within the same region. Based on the observed
      homology between the NH2-terminal module and the membrane proximal (WSXWS
      containing) module of hIL-5R alpha we located this stretch of four amino acid
      residues (D55, D56, Y57 and E58) in the loop region that connects the C and D
      beta-strands on the proposed tertiary structure of the NH2-terminal
      module.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7628441
TI  - LckBP1, a proline-rich protein expressed in haematopoietic lineage cells,
      directly associates with the SH3 domain of protein tyrosine kinase p56lck.
AB  - The Lck tyrosine kinase molecule plays an essential role in T cell activation and
      T cell development. Using the expression cloning technique, we have isolated a
      gene that encodes a molecule, LckBP1, able to associate with murine Lck. Analysis
      of full-length LckBP1 cDNA indicates at least four potentially important
      segments: a four tandem 37 amino acid repeat motif with a potential helix-turn
      helix DNA binding motif; a proline-rich region; a proline-glutamate repeat; and
      an SH3 domain. These four regions are very similar to the human haematopoietic
      specific protein 1 (HS1). Deletion mutant analysis of LckBP1 revealed two proline
      rich regions that permit association with Lck SH3. One region contains prolines
      conserved among HS1 and cortactin, and the other region contains a potential MAP
      kinase recognition site. In vivo association between Lck and LckBP1 was confirmed
      by immunoprecipitation of lysates from a pre-T cell line and adult thymocytes
      using antibodies specific for Lck and LckBP1. LckBP1 is tyrosine phosphorylated
      after T-cell receptor stimulation. The SH3 domain and the potential helix-turn
      helix motif in LckBP1 suggest that this molecule may associate with various
      molecules and function as a DNA binding molecule. The data also suggest that
      LckBP1 mediates intracellular signalling through Lck in T cells.

PMID- 7628442
TI  - Identification and characterization of a new disulfide isomerase-like protein
      (DsbD) in Escherichia coli.
AB  - Previous studies have established that DsbA and DsbC, periplasmic proteins of
      Escherichia coli, are two key players involved in disulfide bond formation. A
      search for extragenic mutations able to compensate for the lack of dsbA function
      in vivo led us to the identification of a new gene, designated dsbD. Lack of DsbD
      protein leads to some, but not all, of the phenotypic defects observed with other
      dsb mutations, such as hypersensitivity to dithiothreitol and to
      benzylpenicillin. In addition, unlike the rest of the dsb genes, dsbD is
      essential for bacterial growth at temperatures above 42 degrees C. Cloning of the
      wild-type gene and sequencing and overexpression of the protein show that dsbD is
      part of an operon and encodes an inner membrane protein. A 138 amino acid
      subdomain of the protein was purified and shown to possess an oxido-reductase
      activity in vitro. Expressing this subdomain in the periplasmic space helped
      restore the phenotypic defects associated with a dsbD null mutation.
      Interestingly, this domain shares 45% identity with the portion of the eukaryotic
      protein disulfide isomerase carrying the active site. We further show that in
      dsbD mutant bacteria the dithiol active sites of DsbA and DsbC proteins are
      mostly oxidized, as compared with wild-type bacteria. Our results argue that DsbD
      generates a reducing source in the periplasm, which is required for maintaining
      proper redox conditions. The finding that overexpression of DsbD leads to a Dsb-
      phenotype, very similar to that exhibited by dsbA null mutants, is in good
      agreement with such a model.

PMID- 7628443
TI  - The molecular chaperone calnexin is expressed on the surface of immature
      thymocytes in association with clonotype-independent CD3 complexes.
AB  - Immature thymocytes express clonotype-independent CD3 complexes that, when
      engaged by anti-CD3 antibodies, can signal CD4-CD8- thymocytes to differentiate
      into CD4+CD8+ cells. Clonotype-independent CD3 complexes consist of CD3
      components associated with an unknown 90 kDa surface protein. We now report the
      surprising finding that this 90 kDa surface protein is the molecular chaperone
      calnexin, an integral membrane protein previously thought to reside only in the
      endoplasmic reticulum (ER). We found that calnexin-CD3 complexes escaping to the
      cell surface utilize interchain associations distinct from those utilized by
      calnexin-CD3 complexes remaining within the ER. Specifically, we demonstrate that
      carbohydrate-mediated luminal domain interactions that are necessary for
      formation of most internal calnexin-CD3 complexes destined to be expressed on the
      cell surface, and we provide evidence that cytoplasmic domain interactions
      between calnexin and CD3 epsilon chains mask calnexin's ER retention signal,
      permitting calnexin and associated proteins to escape ER retention. Thus, the
      present study demonstrates that partial T cell antigen receptor complexes can
      escape the ER of immature thymocytes in association with their molecular
      chaperone to be expressed at low levels on the cell surface where they may
      function as a signaling complex to regulate thymocyte maturation.

PMID- 7628444
TI  - Hsp78, a Clp homologue within mitochondria, can substitute for chaperone
      functions of mt-hsp70.
AB  - Hsp78 is a Clp homologue within mitochondria of Saccharomyces cerevisiae.
      Deletion of HSP78 does not cause any detectable changes in wild type cells, but
      results in a petite phenotype in the ssc1-3 mutant strain carrying a temperature
      sensitive allele of mt-hsp70. When overexpressed in the ssc1-3 mutant strain,
      hsp78 suppresses the defect in mitochondrial protein import under permissive
      conditions in vitro and interacts directly with newly imported polypeptide
      chains. As a molecular chaperone, hsp78 prevents the aggregation of misfolded
      proteins in the matrix of mitochondria under conditions of impaired mt-hsp70
      function. However, unlike misfolded proteins associated with mt-hsp70, hsp78
      bound polypeptides are not efficiently degraded by the ATP-dependent PIM1
      protease. Thus, hsp78 can partially substitute for mt-hsp70 functions in the
      assembly of mitochondria and may be part of a salvage pathway if mt-hsp70 is
      limiting.

PMID- 7628445
TI  - Conservative sorting of F0-ATPase subunit 9: export from matrix requires delta pH
      across inner membrane and matrix ATP.
AB  - In an attempt to understand the mechanisms of sorting of mitochondrial inner
      membrane proteins, we have analyzed the import of subunit 9 of the mitochondrial
      F1F0-ATPase (Su9) from Neurospora crassa, an integral inner membrane protein. A
      chimeric protein was used consisting of the presequence and the first
      transmembrane domain of Su9 fused to mouse dihydrofolate reductase (preSu9(1-112)
      DHFR). This protein attains the correct topology across the inner membrane (Nout
      Cin) following import. The transmembrane domain becomes first completely imported
      into the matrix, where after processing of the presequence, it mediates membrane
      insertion and export of the N-terminal tail. Import and export steps can be
      experimentally dissected into two distinct events. Translocation of the N
      terminal hydrophilic tail out of the matrix was blocked when the presequence was
      not processed, indicating an important role of the sequences and charges flanking
      the hydrophobic domain. Furthermore, export was supported by a delta pH and
      required matrix ATP hydrolysis. Thus the hydrophobic transmembrane domain
      operates as a membrane insertion signal and not as a stop-transfer signal. Our
      findings suggest that several aspects of this sorting process have been conserved
      from their prokaryotic ancestors.

PMID- 7628447
TI  - Mitochondrial import of a cytoplasmic lysine-tRNA in yeast is mediated by
      cooperation of cytoplasmic and mitochondrial lysyl-tRNA synthetases.
AB  - Cytoplasmic tRNA(Lys)CUU is the only nuclear-encoded tRNA of Saccharomyces
      cerevisiae found to be associated with mitochondria. Selective import of this
      tRNA into isolated organelles requires cytoplasmic factors. Here we identify two
      of these factors as the cytoplasmic and mitochondrial lysyl-tRNA synthetases. The
      cytoplasmic enzyme is obligatory for in vitro import of the deacylated, but not
      of the aminoacylated tRNA. We thus infer that it is needed for aminoacylation of
      the tRNA, which is a prerequisite for its import. The mitochondrial synthetase,
      which cannot aminoacylate tRN(Lys)CUU, is required for import of both
      aminoacylated and deacylated forms. Its depletion leads to a total arrest of tRNA
      import, in vitro and in vivo. The mitochondrial lysyl-tRNA synthetase is able to
      form specific and stable RNP complexes with the amino-acylated tRNA. Furthermore,
      an N-terminal truncated form of the synthetase which cannot be targeted into
      mitochondria is unable to direct the import of the tRNA. We therefore hypothesize
      that the cytosolic precursor form of the mitochondrial synthetase has a carrier
      function for translocation of the tRNA across the mitochondrial membranes.
      However, cooperation of the two synthetases is not sufficient to direct tRNA
      import, suggesting the need of additional factor(s).

PMID- 7628446
TI  - The role of the GrpE homologue, Mge1p, in mediating protein import and protein
      folding in mitochondria.
AB  - Mge1p, a mitochondrial GrpE homologue, has recently been identified in the yeast
      Saccharomyces cerevisiae and a role for this protein in precursor import has been
      reported. To dissect the molecular mechanism of Mge1p function, conditional mge1
      mutants were constructed. Cells harbouring mutant mge1 accumulated precursor
      proteins at restrictive temperature. Both kinetics and efficiency of import were
      reduced in mitochondria isolated from strains possessing mutant mge1. Binding of
      mitochondrial-Hsp70 (mt-Hsp70) to incoming precursor proteins was abolished at
      restrictive temperature. Nucleotide-dependent dissociation of mt-Hsp70 from the
      import component MIM44 was reduced in mitochondria from mutant mge1 strains.
      Furthermore, at restrictive temperature an increase of incompletely folded, newly
      imported protein and enhanced protein aggregation was observed in mitochondria
      isolated from the mutant strains. We conclude that Mge1p exerts an essential
      function in import and folding of proteins by controlling the nucleotide
      dependent binding of mt-Hsp70 to substrate proteins and the association of mt
      Hsp70 with MIM44.

PMID- 7628448
TI  - Peroxisomal and mitochondrial carnitine acetyltransferases of Saccharomyces
      cerevisiae are encoded by a single gene.
AB  - Carnitine acetyltransferase (CAT) is present in mitochondria and peroxisomes of
      oleate-grown Saccharomyces cerevisiae. Both proteins are encoded by the same
      gene, YCAT, which encodes a protein with a mitochondrial targeting signal (MTS)
      at the N-terminus, and a peroxisomal targeting signal type 1 (PTS-1) at the C
      terminus. Deletion of both motifs revealed the presence of an additional internal
      targeting sequence. Import of CAT via this internal signal was shown to be
      dependent on PAS10, a protein which is required for the import of PTS-1
      containing proteins. An interaction of PAS10 with this internal targeting signal
      was demonstrated using the yeast two-hybrid technique. Expression of the YCAT
      gene behind a heterologous promoter resulted in loss of peroxisomal targeting,
      indicating that differential targeting is controlled at transcriptional or
      translational level. Determination of the 5'-ends of YCAT mRNAs revealed that
      YCAT transcripts initiating after the first AUG were present in oleate-grown
      cells. These transcripts were virtually absent in acetate- or glycerol-grown
      cells. We propose that in response to oleate, shorter transcripts are produced
      from which the peroxisomal form of CAT is translated, resulting in a CAT protein
      without a MTS, which can be targeted to peroxisomes.

PMID- 7628449
TI  - The membrane of peroxisomes in Saccharomyces cerevisiae is impermeable to NAD(H)
      and acetyl-CoA under in vivo conditions.
AB  - We investigated how NADH generated during peroxisomal beta-oxidation is
      reoxidized to NAD+ and how the end product of beta-oxidation, acetyl-CoA, is
      transported from peroxisomes to mitochondria in Saccharomyces cerevisiae.
      Disruption of the peroxisomal malate dehydrogenase 3 gene (MDH3) resulted in
      impaired beta-oxidation capacity as measured in intact cells, whereas beta
      oxidation was perfectly normal in cell lysates. In addition, mdh3-disrupted cells
      were unable to grow on oleate whereas growth on other non-fermentable carbon
      sources was normal, suggesting that MDH3 is involved in the reoxidation of NADH
      generated during fatty acid beta-oxidation rather than functioning as part of the
      glyoxylate cycle. To study the transport of acetyl units from peroxisomes, we
      disrupted the peroxisomal citrate synthase gene (CIT2). The lack of phenotype of
      the cit2 mutant indicated the presence of an alternative pathway for transport of
      acetyl units, formed by the carnitine acetyltransferase protein (YCAT).
      Disruption of both the CIT2 and YCAT gene blocked the beta-oxidation in intact
      cells, but not in lysates. Our data strongly suggest that the peroxisomal
      membrane is impermeable to NAD(H) and acetyl-CoA in vivo, and predict the
      existence of metabolite carriers in the peroxisomal membrane to shuttle
      metabolites from peroxisomes to cytoplasm and vice versa.

PMID- 7628450
TI  - vnd, a gene required for early neurogenesis of Drosophila, encodes a homeodomain
      protein.
AB  - The development of the central nervous system in Drosophila is initiated by the
      segregation of neuroblasts, the neural progenitors, from the embryonic
      neuroectoderm. This process is guided by at least two classes of genes: the
      achaete-scute complex (AS-C) proneural genes and the neurogenic genes. It has
      been known for some time that loss-of-function mutations in the AS-C result in
      neural hypoplasia and the first observed defect is failure of segregation of a
      fraction of neuroblasts. Loss-of-function mutations at the ventral nervous system
      defective (vnd) locus are known to lead to similar phenotypic defects in early
      neurogenesis. More recently, the vnd locus has been implicated in the regulation
      of the proneural AS-C genes and the neurogenic genes of the Enhancer of split
      complex. In this paper we report the identification of a transcript associated
      with the vnd locus, the transcript distribution in embryogenesis, which is
      compatible with the nervous system mutant phenotypes described for this gene, and
      that the protein product is a member of the NK-2 homeodomain family. We discuss
      these findings within the framework of early Drosophila neurogenesis and the
      known phenotypes associated with the vnd locus.

PMID- 7628451
TI  - Phosphorylation of the adenovirus E1A-associated 300 kDa protein in response to
      retinoic acid and E1A during the differentiation of F9 cells.
AB  - Transcription of the c-jun gene is up-regulated by either retinoic acid (RA) or
      adenovirus E1A during the differentiation of F9 cells. We show here that RA and
      E1A induce phosphorylation of the E1A-associated 300 kDa protein (p300) during
      the differentiation of F9 cells. The region of E1A that is required for
      interaction with cellular protein p300 overlaps with the region of E1A required
      for E1A to induce expression of the c-jun gene. Treatment of F9 cells with RA or
      infection of the cells by adenovirus led to a decrease in the electrophoretic
      mobility of p300. Phosphatase treatment of p300 from RA-treated or adenovirus
      infected F9 cells reversed the changes in migration of p300, indicating that RA-
      and E1A-mediated changes in the mobility of p300 were due to phosphorylation. We
      also found factors, designated DRF1 and DRF2, that bound specifically to a
      sequence element that is necessary and sufficient for RA- and E1A-mediated up
      regulation of the c-jun gene. The mobility of DRF complexes was changed by E1A or
      RA and the complexes were supershifted by addition of a polyclonal p300
      antiserum. Moreover, overexpression of p300 resulted in an increase in the level
      of DRF1 complex. p300 fused to the DNA binding domain of the E2 protein of
      papilloma virus stimulated E2-dependent reporter activity in response to RA or
      E1A in F9 cells. Our results suggest that p300 is part of the DRF complexes, that
      it is differentially phosphorylated in undifferentiated versus differentiated
      cells and that it is likely involved in regulating transcription of the c-jun
      gene during F9 cell differentiation.

PMID- 7628452
TI  - Involvement of SOX proteins in lens-specific activation of crystallin genes.
AB  - We have studied the mechanism of delta 1-crystallin gene activation, which occurs
      early in lens cell differentiation, and have previously shown that an essential
      element of the delta 1-crystallin enhancer is bound by a group of nuclear
      factors, delta EF2, among which delta EF2a is highly enriched in lens cells. In
      this report we show that the cDNA of delta EF2a codes for the chicken SOX-2
      protein (cSOX-2), which is structurally related to the sex-determining factor
      SRY. Sox-2 is expressed at high levels in the early developing lens in both
      chicken and mouse embryos. Overexpression of delta EF2a/cSOX-2 increased delta 1
      crystallin enhancer activity to a plateau in lens cells, but not in fibroblasts,
      consistent with the previously drawn conclusion that delta EF2a activates
      transcription only in concert with another factor present in the lens. This
      result supports the model that SOX proteins act as architectural components in
      the activating complex formed on an enhancer, as indicated for another HMG domain
      protein, lymphoid enhancer binding factor 1 (LEF-1). We also show that SOX
      protein binding is essential for lens-specific promoter activity of the mouse
      gamma F-crystallin gene. This work is the first to show delta- and gamma
      crystallin genes as examples of direct regulatory targets of SOX proteins and
      provides evidence that diversified crystallin genes are regulated, at least
      partly, by a common mechanism.

PMID- 7628453
TI  - The coactivator p15 (PC4) initiates transcriptional activation during TFIIA-TFIID
      promoter complex formation.
AB  - We have analyzed the mechanisms underlying stimulation of transcription by the
      activator GAL4-AH and the recombinant coactivator p15 (PC4). We show that p15
      binds to both double-stranded and single-stranded DNA. Analyses of deletion
      mutants correlates binding to double-stranded DNA with the ability to mediate
      activator-dependent transcription. Consistent with this finding, phosphorylation
      of p15 by casein kinase II inhibits binding to double-stranded DNA and the
      activity of p15. The functional characterization suggests interactions of p15
      with both DNA and components of the TFIID complex. GAL4-AH functions in concert
      with p15 during formation of TFIIA-TFIID-promoter (DA) complexes, as concluded
      from order-of-addition experiments. At limiting TFIID concentrations, the number
      of DA complexes is enhanced. The activator also stimulates transcription
      moderately after DA complex formation, independently of the concentrations of
      general transcription factors.

PMID- 7628454
TI  - Protein-protein interaction via PAS domains: role of the PAS domain in positive
      and negative regulation of the bHLH/PAS dioxin receptor-Arnt transcription factor
      complex.
AB  - Gene regulation by dioxins is mediated by the dioxin receptor-Arnt heterodimer, a
      ligand generated complex of two basic helix-loop-helix (bHLH)/Per-Arnt-Sim (PAS)
      transcription factors. By using dioxin receptor chimeras where the dimerization
      and DNA binding bHLH motif has been replaced by a heterologous DNA binding
      domain, we have detected an ability of Arnt to interact with the dioxin receptor
      via the PAS domain in a mammalian 'hybrid interaction' system. By
      coimmunoprecipitation assays, we have confirmed the ability of PAS domains of the
      dioxin receptor and Arnt to mediate independent heterodimerization in vitro.
      Selectivity for PAS dimerization was noted in our hybrid interaction system, as
      dioxin receptor or Arnt PAS-mediated homodimers were not detected. Surprisingly,
      however, the PAS domain of Per could dimerize with both the dioxin receptor and
      Arnt subunits in vitro, and disrupt the ability of these subunits to form a DNA
      binding heterodimer. Moreover, ectopic expression of Per blocked dioxin
      signalling in mammalian cells. The PAS domains of the dioxin receptor and Arnt
      are therefore novel dimerizing regions critical in formation of a functional
      dioxin receptor-Arnt complex, while the PerPAS domain is a potential negative
      regulator of bHLH/PAS factor function.

PMID- 7628455
TI  - Splicing of cauliflower mosaic virus 35S RNA is essential for viral infectivity.
AB  - A splicing event essential for the infectivity of a plant pararetrovirus has been
      characterized. Transient expression experiments using reporter constructs
      revealed a splice donor site in the leader sequence of the cauliflower mosaic
      virus (CaMV) 35S RNA and three additional splice donor sites within open reading
      frame (ORF) I. All four donors use the same splice acceptor within ORF II.
      Splicing between the leader and ORF II produces an mRNA from which ORF III and,
      in the presence of the CaMV translational transactivator, ORF IV can be
      translated efficiently. The other three splicing events produce RNAs encoding ORF
      I-II in-frame fusions. All four spliced CaMV RNAs were detected in CaMV-infected
      plants. Virus mutants in which the splice acceptor site in ORF II is inactivated
      are not infectious, indicating that splicing plays an essential role in the CaMV
      life cycle. The results presented here suggest a model for viral gene expression
      in which RNA splicing is required to provide appropriate substrate mRNAs for the
      specialized translation mechanisms of CaMV.

PMID- 7628456
TI  - NMR solution structure of a dsRNA binding domain from Drosophila staufen protein
      reveals homology to the N-terminal domain of ribosomal protein S5.
AB  - The double-stranded RNA binding domain (dsRBD) is an approximately 65 amino acid
      motif that is found in a variety of proteins that interact with double-stranded
      (ds) RNA, such as Escherichia coli RNase III and the dsRNA-dependent kinase, PKR.
      Drosophila staufen protein contains five copies of this motif, and the third of
      these binds dsRNA in vitro. Using multinuclear/multidimensional NMR methods, we
      have determined that staufen dsRBD3 forms a compact protein domain with an alpha
      beta-beta-beta-alpha structure in which the two alpha-helices lie on one face of
      a three-stranded anti-parallel beta-sheet. This structure is very similar to that
      of the N-terminal domain of a prokaryotic ribosomal protein S5. Furthermore, the
      consensus derived from all known S5p family sequences shares several conserved
      residues with the dsRBD consensus sequence, indicating that the two domains share
      a common evolutionary origin. Using in vitro mutagenesis, we have identified
      several surface residues which are important for the RNA binding of the dsRBD,
      and these all lie on the same side of the domain. Two residues that are essential
      for RNA binding, F32 and K50, are also conserved in the S5 protein family,
      suggesting that the two domains interact with RNA in a similar way.

PMID- 7628457
TI  - Structure of the dsRNA binding domain of E. coli RNase III.
AB  - The double-stranded RNA binding domain (dsRBD) is a approximately 70 residue
      motif found in a variety of modular proteins exhibiting diverse functions, yet
      always in association with dsRNA. We report here the structure of the dsRBD from
      RNase III, an enzyme present in most, perhaps all, living cells. It is involved
      in processing transcripts, such as rRNA precursors, by cleavage at short hairpin
      sequences. The RNase III protein consists of two modules, a approximately 150
      residue N-terminal catalytic domain and a approximately 70 residue C-terminal
      recognition module, homologous with other dsRBDs. The structure of the dsRBD
      expressed in Escherichia coli has been investigated by homonuclear NMR techniques
      and solved with the aid of a novel calculation strategy. It was found to have an
      alpha-beta-beta-beta-alpha topology in which a three-stranded anti-parallel beta
      sheet packs on one side against the two helices. Examination of 44 aligned dsRBD
      sequences reveals several conserved, positively charged residues. These residues
      map to the N-terminus of the second helix and a nearby loop, leading to a model
      for the possible contacts between the domain and dsRNA.

PMID- 7628459
TI  - Ubiquitin and the enigma of intracellular protein degradation.
AB  - Contrary to widespread belief, the regulation and mechanism of degradation for
      the mass of intracellular proteins (i.e. differential, selective protein
      turnover) in vertebrate tissues is still a major biological enigma. There is no
      evidence for the conclusion that ubiquitin plays any role in these processes. The
      primary function of the ubiquitin-dependent protein degradation pathway appears
      to lie in the removal of abnormal, misfolded, denatured or foreign proteins in
      some eukaryotic cells. ATP/ubiquitin-dependent proteolysis probably also plays a
      role in the degradation of some so-called 'short-lived' proteins. Evidence
      obtained from the covalent modification of such natural substrates as calmodulin,
      histones (H2A, H2B) and some cell membrane receptors with ubiquitin indicates
      that the reversible interconversion of proteins with ubiquitin followed by
      concomitant functional changes may be of prime importance.

PMID- 7628458
TI  - The Agrobacterium tumefaciens virulence D2 protein is responsible for precise
      integration of T-DNA into the plant genome.
AB  - The VirD2 protein of Agrobacterium tumefaciens was shown to pilot T-DNA during
      its transfer to the plant cell nucleus. We analyze here its participation in the
      integration of T-DNA by using a virD2 mutant. This mutation reduces the
      efficiency of T-DNA transfer, but the efficiency of integration of T-DNA per se
      is unaffected. Southern and sequence analyses of integration events obtained with
      the mutated VirD2 protein revealed an aberrant pattern of integration. These
      results indicate that the wild-type VirD2 protein participates in ligation of the
      5'-end of the T-strand to plant DNA and that this ligation step is not rate
      limiting for T-DNA integration.

PMID- 7628460
TI  - Characterization and transcriptional activity of the mouse biliary glycoprotein 1
      gene, a carcinoembryonic antigen-related gene.
AB  - The mouse biliary glycoprotein 1 gene (bgp1) encodes several multifunctional
      glycoprotein isoforms. These glycoproteins represent members of the
      carcinoembryonic antigen (CEA) family which belongs to the immunoglobulin
      superfamily. The Bgp1 glycoproteins function as cell adhesion molecules and
      receptors for the mouse hepatitis viruses. In contrast to CEA, whose
      overexpression has been correlated with cancer progression, the human and mouse
      Bgp proteins are generally down-regulated upon tumor formation. In this study, we
      report on the mouse bgp1 gene organization and transcriptional activation. We
      have isolated phage and cosmid clones encompassing the entire bgp1 coding region.
      This gene consists of nine exons, some of which are subjected to alternative
      splicing producing a minimum of four splice variants. A comparison of the murine
      bgp1 proximal promoter with the human BGP and mouse cea10/bgp3 genes revealed
      sequence conservation of 66% and 95%, respectively. RNase protection assays and
      primer extension analyses indicated that the mouse bgp1 transcriptional start
      site is positioned 240 nucleotides upstream of the ATG translational initiation
      codon, which is 140 nucleotides further upstream than in any other CEA family
      member. The bgp1 promoter is transcriptionally active in reporter gene activation
      in vitro transfection studies and in vivo using a bgp1-containing cosmid clone.
      We identified three putative AP-2 or AP-2-like sites and an upstream stimulatory
      factor (USF) recognition sequence within the proximal mouse bgp1 promoter region
      at positions similar to those used by the human BGP promoter region. These data
      suggest that the regulation of the mouse and human BGP genes may follow some
      common spatial and temporal expression. Interestingly, the bgp1 proximal promoter
      and coding region are also well conserved throughout evolution.

PMID- 7628461
TI  - Biogenesis of the yeast vacuole (lysosome). The use of active-site mutants of
      proteinase yscA to determine the necessity of the enzyme for vacuolar proteinase
      maturation and proteinase yscB stability.
AB  - The activation process of vacuolar proteinases in the yeast Saccharomyces
      cerevisiae via precursor maturation is initiated by the PRA1/PEP4 gene product,
      proteinase yscA. Chromosomal deletion of the PRA1/PEP4 locus leads to
      accumulation of inactive pro-proteinases in the vacuole. Nine active-site
      mutations of proteinase yscA have been constructed in vitro. All these mutations
      lead to the expression of proteinase yscA species in vivo that are inactive
      against the in vitro substrate hemoglobin and the in vivo substrates pro
      proteinase yscB and pro-carboxypeptidase yscY. However, three active-site
      mutations in proteinase yscA sustained the precursor maturation of proteinase
      yscB and carboxypeptidase yscY after exchange of the genomic wild-type allele
      with the respective proteinase yscA mutant alleles. In contrast to yeast strains
      deleted in proteinase yscA, the respective mutants carry out all cellular
      functions that rely on a proteolytically active vacuole. This wild-type behaviour
      of proteinase yscA mutant cells is dependent on the presence of active proteinase
      yscB. Proteinase yscA and proteinase yscB are equally able to fulfil essential
      cellular functions. For instance, either proteinase is able to maintain viability
      under starvation. However, mature proteinase yscB is not stable in the absence of
      proteinase yscA. The wild-type-like conformation of proteolytically inactive
      mutant proteinase yscA proteins stabilizes mature proteinase yscB and thus
      enables continuous maturation of pro-proteinase yscB by active proteinase yscB.
      After inhibition of the proteolytic activity of proteinase yscB in these
      proteinase yscA mutants with phenylmethysulfonyl fluoride or deletion of the PRB1
      gene, maturation of all zymogens investigated in the vacuole, including the
      proteinase yscA mutant proteins, is blocked. The proteolytic activities of the
      vacuole in such a strain can be regained, however, by introduction of a wild-type
      proteinase yscA gene allowing subsequent autocatalytic maturation of wild-type
      pro-proteinase yscA. This indicates that an initial self-activation process of
      proteinase yscA is necessary for the activation of vacuolar zymogens.

PMID- 7628462
TI  - Thyroid hormone modulates apolipoprotein-AI gene expression at the post
      transcriptional level in Hep G2 cells.
AB  - Hyperthyroidism is associated with elevated plasma levels of apolipoprotein AI
      (apo AI). We have examined the effects of 3,3',-5-triiodothyronine on apo AI
      mRNA, transcription run-on activity, apo AI mRNA half-life, and the rate of
      protein synthesis in Hep G2 cells, to understand the molecular mechanism by which
      thyroid hormone regulates apo AI gene expression. Incubation with thyroid hormone
      increased the apo AI and apo AII mRNA concentrations twofold. Cycloheximide alone
      caused a significant increase in apo AI mRNA. Nuclear run-on assays indicate that
      thyroid hormone did not change the rate of the apo AI gene transcription at 6, 12
      or 24 h, showing that thyroid hormone did not modulate apo AI gene transcription.
      Kinetic studies performed in the presence of actinomycin D showed that the half
      life of apo AI mRNA was increased 2-3-fold by thyroid hormone over control cells.
      Thyroid hormone did not change the incorporation of [35S]methionine into
      immunoprecipitable apo AI. Pulse-chase experiments demonstrated that there was no
      change in the secretion and degradation rates of labeled apo AI in response to
      T3. This suggests that thyroid hormone does not affect the catabolism of apo AI
      (degradation or/and uptake) and that translation control strongly influences the
      regulation of apo AI gene expression. The stabilization of apo AI mRNA by thyroid
      hormone and its role in translation remain to be elucidated.

PMID- 7628463
TI  - Electron transfer and spectral alpha-band properties of the di-heme protein
      cytochrome c4 from Pseudomonas stutzeri.
AB  - Cytochrome c4 is a 190-residue protein active in the aerobic and anaerobic
      respiration of several bacteria. We have isolated Pseudomonas stutzeri (ATCC no.
      11607) cytochrome c4 by an optimized growth procedure following factorial design.
      The ultraviolet/visible spectra of reduced cytochrome c4 have a composite
      alpha/beta band which can be resolved into six components. One of these seems to
      be specific for the high-potential heme group. The kinetics for full oxidation
      and reduction with the two inorganic redox couples, [Co(terpy)2]2+/3+ and
      [Co(bipy)3]2+/3+, is formally compatible with either bi- or tri-exponential
      kinetics. The former would be in line with weak interaction between the heme
      groups, the latter with notable interaction effects. Arguments in favour of the
      latter and a cooperative two-electron transfer pattern are given. All phases are
      approximately proportional to the Co-complex concentration, implying that
      intramolecular electron transfer in this time range is unlikely. The rate
      constants are in the range (0.7-80) x 10(4) M-1 s-1 at pH = 7.6 (Tris) and 0.1 M
      NaCl and very little dependent on the ionic strength in the range 0.1-0.3 M. The
      reduction potentials could be calculated from the forward and reverse rate
      constant ratios. The values are 241 +/- 5 and 328 +/- 2 mV (Nernst hydrogen
      electrode) if bi-exponential kinetics is used and interaction between the heme
      groups disregarded. The intrinsic microscopic reduction potential values are
      closer when the tri-exponential, cooperative model is used as this model
      transfers 30-40 mV to electrostatically dominated interaction potentials. The
      overall electron transfer pattern can be related to the recently determined
      crystal structure of the P. stutzeri cytochrome c4.

PMID- 7628464
TI  - Overproduction, purification and characterization of the cellulose-binding domain
      of the Erwinia chrysanthemi secreted endoglucanase EGZ.
AB  - EGZ is the major endoglucanase secreted by Erwinia chrysanthemi. Functional
      characterization indicates that it is made of a catalytic N-terminal domain
      linked to a C-terminal cellulose-binding domain (CBD) by a Ser/Thr-rich linker. A
      chimeric plasmid, in which the CBD-encoding region was fused downstream of the
      ompA signal sequence, was constructed and introduced into Escherichia coli. This
      allowed for the production of processed and disulfide-bonded CBD, mostly
      recovered from the culture supernatant of E. coli. One-dimensional NMR analysis
      of the purified CBD reveals that it folds into a well-structured domain.
      Moreover, comparison with the one-dimensional NMR analysis of full-length EGZ
      strongly suggests that the CBD folds autonomously, providing experimental support
      for the existence of domains of EGZ.

PMID- 7628465
TI  - Amino acid sequence of spinach ferredoxin:thioredoxin reductase catalytic subunit
      and identification of thiol groups constituting a redox-active disulfide and a
      [4Fe-4S] cluster.
AB  - Ferredoxin:thioredoxin reductase is a [4Fe-4S] protein involved in the light
      regulation of carbon metabolism in oxygenic photosynthesis. This enzyme catalyses
      the reduction of thioredoxins with light-generated electrons.
      Ferredoxin:thioredoxin reductase is composed of two dissimilar subunits, a
      catalytic subunit, and a variable subunit. The catalytic subunit of spinach
      ferredoxin:thioredoxin reductase, which contains the redox-active disulfide
      bridge, was sequenced by conventional protein sequencing techniques and the
      functional roles of all eight cysteine residues were examined by chemical
      modifications. The polypeptide chain with a calculated molecular mass of 12,959
      Da consists of 113 amino acids and has a calculated isoelectric point of 5.30.
      Six of the eight cysteine residues are clustered as Cys-Pro-Cys and Cys-His-Cys
      groups. Cys19 and Cys27 are free cysteines with no catalytic function, Cys54 and
      Cys84 constitute the redox-active disulfide bridge of the active site, and the
      remaining four, Cys52, Cys71, Cys73, and Cys82 bind the Fe-S cluster.

PMID- 7628466
TI  - Structure and function of mutant Arg44Lys of 4-hydroxybenzoate hydroxylase
      implications for NADPH binding.
AB  - Arg44, located at the si-face side of the flavin ring in 4-hydroxybenzoate
      hydroxylase, was changed to lysine by site-specific mutagenesis. Crystals of
      [R44K]4-hydroxybenzoate hydroxylase complexed with 4-hydroxybenzoate diffract to
      0.22-nm resolution. The structure of [R44K]4-hydroxybenzoate hydroxylase is
      identical to the wild-type enzyme except for local changes in the vicinity of the
      mutation. The peptide unit between Ile43 and Lys44 is flipped by about 180
      degrees in 50% of the molecules. The phi, psi angles in both the native and
      flipped conformation are outside the allowed regions and indicate a strained
      conformation. [R44K]4-Hydroxybenzoate hydroxylase has a decreased affinity for
      the flavin prosthetic group. This is ascribed to the lost interactions between
      the side chain of Arg44 and the diphosphoribose moiety of the FAD. The
      replacement of Arg44 by Lys does not change the position of the flavin ring which
      occupies the same interior position as in wild type. [R44K]4-Hydroxybenzoate
      hydroxylase fully couples flavin reduction to substrate hydroxylation. Stopped
      flow kinetics showed that the effector role of 4-hydroxybenzoate is largely
      conserved in the mutant. Replacement of Arg44 by Lys however affects NADPH
      binding, resulting in a low yield of the charge-transfer species between reduced
      flavin and NADP+. It is inferred from these data that Arg44 is indispensable for
      optimal catalysis.

PMID- 7628467
TI  - Synthesis, three-dimensional structure, and specific 15N-labelling of the
      streptococcal protein G B1-domain.
AB  - The 55-amino-acid B1-domain of the streptococcal protein G shows a high binding
      affinity to IgG isolated from a wide range of mammalian species. Since the B1
      domain forms an extremely stable globular folding unit containing the major
      secondary structure elements and is devoid of proline residues and disulfide
      bridges, it is also a useful tool for protein folding and stability studies. Its
      small size makes this protein an ideal candidate for production by chemical
      synthesis, allowing incorporation of non-natural amino acids with the possibility
      of assessing the influence of such residues on both the functional and structural
      characteristics of proteins. In this study, we employed three successive chemical
      syntheses of the B1-domain in order to define the optimal conditions of coupling
      and protection. The stepwise solid-phase methodology using the
      tertbutyloxycarbonyl/benzyl strategy was used for this purpose. First, the
      sequence assembly difficulties were evaluated. After analyzing of the problems
      found during assembly, a second optimized synthesis was performed leading to
      formation of a synthetic B1-domain with a higher yield; the synthetic B1-domain
      was completely functional in its binding properties to IgG. Three orthogonal
      purification steps (gel-permeation, reverse-phase and ion-exchange HPLC) were
      required to obtain a sample suitable for structural analysis by high-resolution
      NMR. This study led to the conclusion that the synthetic B1-domain adopts a three
      dimensional structure identical to that of the molecule obtained by recombinant
      techniques [Gronenborn, A.M., Filpula, D. R., Essig, N. Z., Achari, A., Whitlow,
      M., Wingfield, P. T. & Clore, G. M. (1991) Science 253, 657-661]. To demonstrate
      the usefulness of the chemical approach for the specific introduction of labelled
      amino acids in the primary structure, fourteen alpha-15N-labelled amino acids
      were incorporated at selected critical positions during the third synthesis. This
      analog is the first in a series of molecules planned to study in detail the
      folding dynamics of the B1-domain.

PMID- 7628468
TI  - Molecular chaperones protect against glycation-induced inactivation of glucose-6
      phosphate dehydrogenase.
AB  - Glucose-6-phosphate dehydrogenase is inactivated slowly by reaction with sugars
      (glycation), a process thought to be important in the development of diabetic
      complications. A major protein from the ocular lens, alpha-crystallin. which
      exhibits some chaperone-like properties, protects against this inactivation. The
      well-known molecular chaperone GroEL (chaperonin 60 from Escherichia coli) also
      protects. On a molar basis, alpha-crystallin is better than GroEL at protecting
      against glycation-induced inactivation of glucose-6-phosphate dehydrogenase. The
      relative amounts of enzyme/chaperone indicate that each molecule of alpha
      crystallin binds two molecules of the damaged enzyme. This supports the view that
      alpha-crystallin has a chaperone-like structure as well as a chaperone-like
      function.

PMID- 7628469
TI  - Changes in the iron coordination sphere of Fe(II) lipoxygenase-1 from soybeans
      upon binding of linoleate or oleate.
AB  - Fe K-edge X-ray absorption spectra of the non-heme iron constituent of
      lipoxygenase-1 from soybeans were obtained. The spectrum of 2.5 mM Fe(II)
      lipoxygenase, mixed with 1.2 M linoleate in the absence of O2, was compared to
      the spectrum of the native (i.e. untreated) enzyme. In the lipoxygenase-linoleate
      complex, an edge shift to lower energy was observed. This indicated that the iron
      ligand distances in this complex are slightly longer than those in the untreated
      enzyme species. The extended X-ray absorption fine structure spectrum of Fe(II)
      lipoxygenase, prepared by anaerobic reduction of 2.5 mM Fe(II) lipoxygenase with
      1.2 M linoleate, was very similar to the spectrum of the anaerobic lipoxygenase
      linoleate complex. We conclude that the conformational differences between the
      iron coordination spheres of native and cycled Fe(II) lipoxygenase must be
      ascribed to the presence of linoleate, and not to changes in the enzyme that
      occur only after one cycle of oxidation and reduction. Furthermore, spectra of
      2.5 mM Fe(II) lipoxygenase mixed with 1.2 M oleate, either in the absence or in
      the presence of O2, were also identical to the spectrum of the Fe(II)
      lipoxygenase-linoleate complex. This finding is in agreement with our observation
      that oleate is a competitive inhibitor of the lipoxygenase reaction. Moreover,
      the similarity of the lipoxygenase-oleate complexes in the presence and absence
      of O2 excludes the possibility that O2 binding to the iron cofactor is induced
      upon binding of a fatty acid to lipoxygenase.

PMID- 7628470
TI  - Purification and characterization of rat skeletal muscle acetyl-CoA carboxylase.
AB  - An acetyl-CoA carboxylase has been purified from rat hindlimb muscle using
      ammonium sulfate fractionation and avidin-Sepharose affinity chromatography.
      SDS/PAGE of the isolated enzyme showed a major protein band at approximately 272
      kDa and a minor band at 265 kDa. The liver acetyl-CoA carboxylase gave a major
      protein band at 265 kDa and a minor band at 280 kDa. Adipose tissue acetyl-CoA
      carboxylase migrated to the 265-kDa position on the gel. Western blots performed
      using streptavidin-alkaline-phosphatase suggest that the bands from the three
      tissues contain biotin. The present study has characterized the muscle and
      adipose tissue enzymes under steady-state kinetics and determined Michaelis
      constants for the substrates. The activation constant for citrate, an essential
      activator for both preparations, was 2.13 +/- 0.05 mM for the muscle enzyme and
      3.02 +/- 0.12 mM for adipose tissue (P < 0.01). The Km values for the muscle
      acetyl-CoA carboxylase compared to the adipose tissue acetyl-CoA carboxylase
      were: ATP, 57.6 +/- 0.9 microM compared to 106.5 +/- 2.6 microM, P < 0.01; acetyl
      CoA, 31.7 +/- 1.5 microM compared to 21.5 +/- 1.0 microM, P < 0.01; bicarbonate,
      2.25 +/- 0.10 mM compared to 2.73 +/- 0.29 mM, P > 0.05. The muscle acetyl-CoA
      carboxylase was inhibited by malonyl-CoA (Ki = 10.6 +/- 1.0 microM) and palmitoyl
      CoA (Ki = 2.2 +/- 0.3 microM). These properties are consistent with the
      hypothesis that regulation of acetyl-CoA carboxylase plays an important role in
      governing the rate of fatty acid oxidation in the skeletal muscle.

PMID- 7628471
TI  - An infrared investigation of palmitoyl-coenzyme A and palmitoylcarnitine
      interaction with perdeuterated-chain phospholipid bilayers.
AB  - Mixtures of di-(perdeuteropalmitoyl)-sn-glycero-3 choline ([2H62]Pam2GroPCho)
      with palmitoylcarnitine or palmitoyl-CoA in aqueous suspension have been examined
      by Fourier-transform infrared spectroscopy. The C-H (or C-D) region of the
      spectrum shows that an order-disorder transition exists in pure aqueous
      palmitoylcarnitine at 45 degrees C; palmitoylcarnitine mixes with
      [2H62]Pam2GroPCho without perturbing the gel-fluid transition of the phospholipid
      even at [2H62]Pam2GroPCho/palmitoylcarnitine 1:2 molar ratios; and palmitoyl-CoA,
      however, at similar proportions, smears out the [2H62]Pam2GroPCho transition as
      detected from C-D stretching vibrations. Relevant data from the carbonyl region
      include; the high-frequency (non-hydrogen bound) carbonyl subpopulation, but not
      the low frequency one, detects the gel-to-fluid transition of the phospholipid;
      the carbonyl region detects the thermotropic transition over a wider temperature
      range than the methylene stretching region, i.e. detects changes starting well
      below and ending several degrees above the methylene transition temperature, and
      a significant interaction may occur between some coenzyme A group and the
      carbonyl groups of the phospholipid. The latter interaction may contribute to
      explain the coenzyme A/carnitine exchange during mitochondrial fatty acid import.

PMID- 7628472
TI  - The effect of free DNA on the interactions of the estrogen receptor bound to
      hormone, partial antagonist or pure antagonist with target DNA.
AB  - Interactions between the lamb uterine estrogen receptor occupied by estradiol, 4
      hydroxytamoxifen (a non-steroidal partial estrogen antagonist) or ICI 164,384 (a
      steroidal pure estrogen antagonist), and the vitellogenin A2 estrogen-response
      element (vit ERE) were compared using a biotinylated 25-base all-palindromic
      double-stranded oligonucleotide, containing vit ERE (b-ERE), which allowed
      isolation of the b-ERE.receptor.[3H]ligand assembly on streptavidin-Sepharose.
      The results of saturation analyses of the three receptor.[3H]ligand complexes by
      increasing amounts of b-ERE were quite similar for the proportion of complexes
      able to interact with b-ERE (which varied from 30% to 65% according to
      experiments) and for the equilibrium dissociation constant [Kd (0 degree C)
      approximately 1.2 nM, assuming that the receptor interacted as a dimer with b
      ERE]. With each ligand, receptor binding to ERE did not change the rate of ligand
      dissociation from the receptor at 20 degrees C. The rate of estrogen receptor
      dissociation from b-ERE, measured at 20 degrees C in the presence of a given
      concentration of ERE, did not vary according to the ligand bound to the receptor;
      however, this dissociation rate increased linearly over the ERE concentration
      range (0.5-10 microM). The experimental rate constant (k-) of estrogen receptor
      dissociation from b-ERE appeared to be the sum of the basal dissociation-rate
      constant (k degrees - approximately 0.011 min-1), corresponding to spontaneous
      dissociation which would occur in the absence of ERE, and of the ERE-induced
      dissociation-rate constant, proportional to the used concentration of ERE (ki-
      approximately 4500 CERE M-1 min-1, where CERE is the molar concentration of ERE).
      Non-target DNA also induced receptor dissociation from b-ERE, but its efficiency
      was 6-10-fold lower than that of ERE. We conclude that, the two antiestrogens are
      as efficient as estradiol in promoting estrogen receptor binding to a single vit
      ERE; the low or nil ability of antiestrogens to induce estrogenic responses is
      probably not linked with the receptor DNA-binding step; DNA binding does not seem
      to affect the conformation of the filled hormone-binding site of the receptor at
      20 degrees C; interactions of receptor dimers with DNA seems to proceed by direct
      transfer of receptor dimers between DNA strands.

PMID- 7628473
TI  - Identification of residues potentially involved in the interactions between
      subunits in yeast alcohol dehydrogenases.
AB  - The lack of crystal structure for tetrameric yeast alcohol dehydrogenases (ADHs)
      has precluded, until now, the identification of the residues involved in subunit
      contacts. In order to address this question, we have characterized the thermal
      stability and dissociation propensity of native ADH I and ADH II isozymes as well
      as of several chimeric (ADH I-ADH II) enzymes. Three groups of substitutions
      affecting the thermostability have been identified among the 24 substitutions
      observed between isozymes I and II. The first group contains a Cys277-->Ser
      substitution, located at the interface between subunits in a three-dimensional
      model of ADH I, based on the crystallographic structure of the dimeric horse
      liver ADH. In the second group, the Asp236-->Asn substitution is located in the
      same interaction zone on the model. The stabilizing effect of this substitution
      can result from the removal of a charge repulsion between subunits. It is shown
      that the effect of these two groups of substitutions correlates with changes in
      dissociation propensities. The third group contains the Met168-->Arg substitution
      that increases the thermal stability, probably by the formation of an additional
      salt bridge between subunits through the putative interface. These data suggest
      that at least part of the subunit contacts observed in horse liver ADH are
      located at homologous positions in yeast ADHs.

PMID- 7628474
TI  - Mammalian dihydroorotase; secondary structure, and interactions with other
      proteolytic fragments from the multienzyme polypeptide CAD.
AB  - We have purified mammalian dihydroorotase as a polypeptide fragment of 46 kDa
      from an elastase digest of CAD, the 240-kDa multienzyme that catalyses the first
      three reactions of pyrimidine biosynthesis. The thermal unfolding of the domain
      was analysed through the change in circular dichroism, indicating a sharp
      transition at 45 degrees C in which most of the native alpha-helix is lost.
      Although there is good evidence that the fragments associate as dimers in
      solution, chemical cross-linking was only possible when the dihydroorotase domain
      was included in a larger proteolytic fragment of 190-195 kDa. Cross-linking of
      the isolated domain yielded a species that appeared to result from links between
      two or more sub-domains, and did not yield the expected 90-kDa dimer of
      dihydroorotase. We speculate that the presence of other folded regions of CAD
      stabilises the interactions between dihydroorotase domains.

PMID- 7628475
TI  - Mutational effects on the spectroscopic properties and biological activities of
      oxidized bovine adrenodoxin, and their structural implications.
AB  - Of the aromatic 1H-NMR signals of oxidized bovine adrenodoxin only those of His56
      showed intrinsic chemical shift changes upon replacement of Tyr82 by Ser or Leu,
      that must arise from a loss of a through-space ring-current effect of the
      tyrosine ring in these mutants. Thus, of the three His residues contained in
      adrenodoxin, His56 is closest to Tyr82, and hence to the highly acidic
      determinant region of adrenodoxin that is the interaction site for adrenodoxin
      reductase and P-450. The strong dependence of the fluorescence intensity of Tyr82
      on the residue in position 56 supported this observation. As a consequence of
      this, the effects of replacement of His56 by Gln or Thr on cytochrome c reduction
      and cytochromes P-450(11 beta) (CYP11B1)-dependent and P-450scc (CYP11A1)
      dependent substrate conversions were studied. No influence on Vmax values was
      observed for all reactions mediated by the mutants, implying His56 does not play
      a decisive role in the intramolecular or intermolecular electron transfer. In
      contrast, the Km values were increased, as was the Ks value for binding of
      CYP11A1 to the [H56T]adrenodoxin. The secondary structure deduced from further
      NMR data of adrenodoxin was compared with that of other ferredoxins. Tyr82 is in
      a region of the molecule containing no secondary-structure elements. The data for
      Tyr82 are in keeping with the biological activities and suggests it is in a
      flexible, solvent-exposed region of the molecule.

PMID- 7628476
TI  - Expression, purification and characterisation of the product from the Bacillus
      subtilis hemD gene, uroporphyrinogen III synthase.
AB  - Uroporphyrinogen III synthase, the product of the hemD gene, is the enzyme
      responsible for the cyclisation of the linear tetrapyrrole, hydroxymethylbilane.
      The hemD gene isolated from Bacillus subtilis was manipulated by PCR to enable
      direct cloning behind a synthetic ribosome-binding site downstream of tandem
      bacteriophage lambda PR and PL promoters in a pCE30-derived vector. Following
      thermal induction of transcription, the resulting plasmid (pPS21) directed the
      synthesis of uroporphyrinogen III synthase. The protein produced was soluble and
      was readily purified. Pure uroporphyrinogen III synthase is monomeric with an
      isoelectric point of 4.1 and an optimum pH for activity of 8.3. Its specific
      activity by assay using synthetic hydroxymethylbilane as substrate is 565 units
      mg-1 and the Km for this substrate is 330 +/- 30 nM. The N-terminal sequence of
      the enzyme is Met-Glu-Asn-Asp-Phe-Pro-Leu, in agreement with the gene-derived
      sequence. Studies based on amino acid modifications suggest that arginine, lysine
      and probably histidine residues are essential for the activity of
      uroporphyrinogen III synthase. Significantly, this synthase from B. subtilis is
      substantially more thermostable than the enzymes from previously studied sources.

PMID- 7628477
TI  - ADP-ribosylation of Arg28 and Arg206 on the actin molecule by chicken arginine
      specific ADP-ribosyltransferase.
AB  - We reported previously on ADP-ribosylation of actins by chicken arginine-specific
      ADP-ribosyltransferase in vitro and in situ and the inhibition of actin
      polymerization by this modification [Terashima, M., Mishima, K., Yamada, K.,
      Tsuchiya, M., Wakutani, T. & Shimoyama, M. (1992) Eur. J. Biochem. 204, 305-311].
      In the present study, we determined amino acid residues of ADP-ribosylation
      site(s) in globular (G-) and filamentous (F-) actins and examined the molecular
      basis of the modification of actin. Arginine-specific ADP-ribosylation occurred
      at Arg28 and Arg206 in G-actin, but only at Arg28 in F-actin. ADP-ribosylation of
      Arg206, located on the pointed end of the actin molecule, significantly blocked
      the interaction with deoxyribonuclease I. These results indicate that Arg206 in G
      actin may be involved in actin polymerization. ADP-ribosylation of Arg28, located
      on the outer surface of actin molecule, did not affect the binding activity with
      myosin subfragment-1, that is thought to interact through the N-terminal amino
      acid residues of G-actin. ADP-ribosylation at both Arg28 and Arg206 of G-actin
      had no apparent effect on the intrinsic ATPase activity. We concluded from this
      study that ADP-ribosylation of Arg206 in G-actin causes the inhibition of actin
      polymerization, and that ADP-ribosylation of Arg28 occurs in F-actin.

PMID- 7628478
TI  - Progress-curve analysis shows that glucose inhibits the cellotriose hydrolysis
      catalysed by cellobiohydrolase II from Trichoderma reesei.
AB  - NMR spectroscopy and HPLC were used to investigate the hydrolysis of cellotriose
      by cellobiohydrolase II from Trichoderma reesei. Substrate and product
      concentrations were followed as a function of time. Progress curves were
      calculated by forward numerical integration of the full kinetic equations and
      were fitted to the experimental data. Binding and rate constants were obtained
      from this fit, whereby no initial slope or Michaelis-Menten approximation was
      used. The progress curves from a single experiment sufficed to produce agreement
      with the Michaelis-Menten model (eight experiments). The absence of a kinetic
      isotope effect was proven. The progress-curve analysis showed that a simple
      degradation model cannot describe the experimental time-courses at substrate
      concentrations greater than 1 mM. A model containing competitive inhibition from
      cellobiose as well as non-competitive inhibition from glucose was developed. This
      four-parameter model accurately reproduces about 1000 experimental data points
      covering five orders of magnitude in oligosaccharide concentrations. Glucose
      binding to the enzyme/cellotriose complex retards, in a non-competitive fashion,
      cellotriose hydrolysis by at least a factor of 30. A structural model for the non
      competitive inhibition is discussed. The NMR experiment also produced individual
      progress curves for the alpha and beta anomers. The beta anomer of cellotriose
      was degraded 2.5-times faster than the alpha anomer.

PMID- 7628479
TI  - Purification of Paracoccus denitrificans cytochrome c552 and sequence analysis of
      the gene.
AB  - Unlike mitochondria, many bacteria use a large repertoire of c-type cytochromes
      in different branches of their electron transport system. Among the many
      cytochromes c present in the soil bacterium Paracoccus denitrificans, a membrane
      bound cytochrome (c552) has been suggested to mediate the electron transport
      between the cytochrome bc1 complex and cytochrome-c oxidase [Berry, E. A. &
      Trumpower, B. L. (1985) J. Biol. Chem. 260, 2458-2467]. We have purified this
      cytochrome from cytoplasmic membranes, and cloned and sequenced its gene, cycM.
      Sequence analysis reveals that, while its C-terminal portion is highly similar to
      type-I cytochromes c, its N-terminal part contains a hydrophobic segment
      providing membrane attachment. In addition, we present immunological evidence for
      its functional role in respiration.

PMID- 7628480
TI  - Separable binding sites for the natural agonist endothelin-1 and the non-peptide
      antagonist bosentan on human endothelin-A receptors.
AB  - A three-dimensional model for the transmembrane domains of human endothelin-A
      receptor was built using structural information from bacteriorhodopsin and
      sequence alignment to other guanine-nucleotide-binding regulatory(G) protein
      coupled receptors. Based on this model, 18 amino acids located at the inside of
      the receptor were mutated and analyzed for binding of the natural ligand
      endothelin-1 and bosentan, a recently described potent orally active endothelin
      antagonist [Clozel, M., Breu, V., Gray, G., Kalina, B., Loffler, B.-M., Burri,
      K., Cassal, J.-M., Hirth, G., Muller, M., Neidhart, W. & Ramuz, H. (1994)
      Pharmacological characterization of bosentan, a new potent orally active
      nonpeptide endothelin receptor antagonist, J. Pharmacol. Exp. Ther. 270, 228
      235]. Mutation of Gly97, Lys140, Lys159, Gln165 and Phe315, located in
      transmembrane region 1, 2, 3, 3, and 6, respectively, caused reduced specific
      binding of 125I-labelled endothelin-1, despite an expression level similar to
      wild-type endothelin-A receptor. Mutation of Tyr263, Arg326 and Asp351 preserved
      endothelin-1 binding but caused reduced binding of bosentan. These amino acids,
      located on transmembrane regions 5, 6 and 7, respectively, are conserved among
      endothelin-A and endothelin-B receptors but not in other G-protein-coupled
      receptors. These observations demonstrate a dissociation of the binding site for
      the peptidic natural agonist endothelin-1 and the synthetic non-peptide
      antagonist bosentan. They provide the molecular basis for bosentan being a
      specific antagonist for both, endothelin-A as well as endothelin-B receptors and
      may in combination with studies on structure/activity relationship support the
      design of novel and more potent endothelin receptor antagonists.

PMID- 7628481
TI  - A soluble protein negatively regulates phospholipase D activity. Partial
      purification and characterization.
AB  - Phosphatidylcholine-specific phospholipase D (PLD) is an important signalling
      phospholipase in mammalian cells. Recently, PLD activity has been shown to be
      positively regulated by the GTP-binding protein ARF (ADP-ribosylating factor). In
      the present work, we document the presence of a factor negatively regulating PLD
      activity in bovine brain cytosol. The inhibitory factor is characterized as a
      large protein or a complex of proteins with a molecular mass higher than 300 kDa.
      Using permeabilized and pre-permeabilized HL-60 cells depleted of their cytosol,
      we demonstrate that the inhibitor acts on GTP[S]-stimulated PLD activity. This
      effect is immediate, persistent and dose dependent for GTP[S]-stimulated PLD.
      Different possibilities for a mechanism of action of the inhibitory factor on the
      regulation of GTP binding of ARF were investigated. This inhibitory factor is not
      the guanine-dissociating inhibitor (GDI) for the small G-binding proteins Rho
      (Rho-GDI), reported to be a PLD inhibitor, since specific antibodies against this
      protein did not recognize a protein in the peak containing the inhibitory factor
      for PLD activity. Furthermore, the inhibitory factor does not prevent the binding
      of GTP[S] to ARF in the presence of HL-60 membranes. This excludes its possible
      role as an inhibitor of an ARF/guanine exchange factor. The inhibitory factor not
      only inhibits a pathway of PLD through GTP[S] activation in particular of the
      small GTP-binding protein, ARF, but it also inhibits PLD activated via either
      protein kinase C (PKC) or tyrosine kinase activation. The inhibitory factor also
      decreases PLC activity and this effect seems to be secondary to the inhibition of
      PLD activity. We discuss a mechanism of action of the inhibitor on PLD and the
      importance of this enzyme activity for membrane traffic.

PMID- 7628482
TI  - Regulation of mammalian ornithine decarboxylase. Studies on the induction of the
      enzyme by hypotonic stress.
AB  - One of the cellular responses to hypotonic stress is a marked induction of a key
      regulatory enzyme in the polyamine biosynthetic pathway, i.e. ornithine
      decarboxylase (ODC). This increase in ODC activity appears to be a physiological
      response since the elevated putrescine production seen after the hypotonic shock
      renders the cells less sensitive to the decrease in osmolarity. In the present
      study, we have investigated the mechanisms by which the hypotonicity may induce
      ODC activity. We provide support for a translational mechanism, closely related
      to the polyamine-mediated feedback regulation of ODC synthesis. In addition, we
      have examined whether the long G+C-rich 5' untranslated region of the ODC mRNA,
      which has been demonstrated to negatively affect the translatability of the
      message, is of any importance for the induction of ODC by hypotonic stress.
      Chinese hamster ovary (CHO) cells expressing ODC mRNA, with or without the 5'
      untranslated region, were isolated after transfecting ODC-deficient CHO cells
      with the appropriate constructs. Hypotonic treatment of the stable transfectants,
      however, revealed no major difference in ODC induction between the cells
      expressing a full-length ODC mRNA and those expressing an ODC mRNA deleted of its
      5' untranslated region, demonstrating that this part of the message was not
      essential for the osmotic effects on ODC expression.

PMID- 7628483
TI  - Inter-species DNA polymerase delta chimeras are functional in Saccharomyces
      cerevisiae.
AB  - The catalytic subunits of DNA polymerase delta of Schizosaccharomyces pombe and
      Saccharomyces cerevisiae share over 50% identity. The capability of S. pombe DNA
      polymerase delta to complement two thermosensitive mutants of S. cerevisiae was
      studied in vivo and it was determined that complementation was allele dependent.
      However, DNA polymerase delta from S. pombe did not restore growth of a S.
      cerevisiae strain containing a disrupted chromosomal copy of the POL3 gene that
      encodes DNA polymerase delta. To identify the regions of DNA polymerase delta
      responsible for species-specific interactions, we constructed different chimeras
      with S. cerevisiae and S. pombe DNA polymerase delta genes. The growth of a S.
      cerevisiae strain with a disrupted chromosomal POL3 gene was studied after
      transformation with plasmids expressing different chimeras. A 1254-bp region
      located in the 3' region of the S. cerevisiae POL3 gene is responsible for
      species-specific functions.

PMID- 7628484
TI  - Inversion of lipase stereospecificity for fluorogenic alkyldiacyl glycerols.
      Effect of substrate solubilization.
AB  - We synthesized enantiomeric 1-O-alkyl-2,3-diacyl-sn-glycerol and 3-O-alkyl-1,2
      diacyl-sn-glycerol containing pyrene as a fluorescent reporter and the
      trinitrophenylamino residue as a fluorescence quencher; both reporter groups were
      covalently bound to the omega end of the acyl chains at positions sn-2 and sn
      3(1), respectively. The fluorescence of the intact substrate molecules was very
      low. Chemical or enzymic release of the fatty acyl chains lead to fluorescence
      dequenching. The rate of lipolysis could be measured from the time-dependent
      increase in fluorescence intensity. We used the respective substrates for the
      continuous determination of activity and stereopreference of four different
      microbial lipases from Chromobacterium viscosum, Candida rugosa, Pseudomonas sp.,
      Rhizopus arrhizus, as well as cutinase from Fusarium solani and lipoprotein
      lipase from bovine milk. The stereopreference of the lipases depended, in
      general, on how the substrate was solubilized in the reaction medium. All lipases
      under investigation preferentially hydrolysed the sn-1 acyl ester bond, if the
      lipid analog was dispersed in albumin-containing Tris/HCl buffer in the absence
      of detergent or organic solvent. In mixtures of 1:1 (by vol.) water/ethanol, the
      enzymes showed higher activity toward the sn-3 acyl ester bond, except for
      lipoprotein lipase which preferred the sn-1 acyl isomer under all conditions
      tested. Different stereopreferences were observed with the different lipases if
      the substrate was solubilized by amphiphiles (micelles of N-dodecyl-N,N-dimethyl
      3-ammonio-1-propanesulfonate). C. rugosa lipase and F. solani cutinase showed
      high stereopreference for the sn-3 acyl ester, whereas Pseudomonas sp. lipase and
      C. viscosum lipase hydrolysed both enantiomers at similar rates. From
      spectroscopic studies, it can be inferred that the conformation of the
      fluorescent lipids is probably similar in water, mixtures of water and organic
      solvents, and in micelles. The possible effects of reaction conditions on
      substrate accessibility and enzyme conformation on stereoselectivity of the
      respective lipases are discussed.

PMID- 7628485
TI  - Hen-egg-white lysozyme modified with histamine. State of the imidazolylethyl
      group covalently attached to the binding site and its effect on the sugar-binding
      ability.
AB  - The chemical modification of Asp101 which is located at the upper end-most site
      (site A) of the binding cleft of hen egg white lysozyme affects the sugar residue
      binding of the midmost site (site C) in addition to that of site A, and results
      in the considerable decrease in the enzymic activity [Fukamizo, T., Hayashi, K. &
      Goto, S. (1986) Eur. J. Biochem. 158, 463-467]. In the present study, Asp101 was
      modified with histamine and converted to [2-imidazol-4(5)-ylethyl]asparagine.
      Contrary to the findings described above, the specific activity of the modified
      lysozyme was higher than that of the native lysozyme by a factor of about two,
      and the loss of sugar residue binding ability caused by the modification was
      found to be restricted to site A. From the H-NMR spectra of the modified
      lysozyme, the pKa value of the imidazolylethyl group covalently attached to
      Asp101 was 7.1, and was higher than that of N-acetylhistidinemethylamide (6.65).
      This indicates that the imidazolylethyl moiety is not exposed to the solvent but
      adheres to the surface of the lysozyme molecule in an unidentified manner. When N
      acetylglucosamine trisaccharide [GlcNAc)3] was added to the modified lysozyme,
      the 1H-NMR signals of H2 and H4 of the imidazolylethyl group were strongly
      affected. This indicates that the imidazolylethyl moiety is located near
      (GlcNAc)3 binding region. When the H gamma signal of Ile98 was saturated, nuclear
      Overhauser effects were observed on H2 and H4 resonances of the imidazolylethyl
      moiety. NOE was also observed on the signal of Trp63 H6 upon the saturation of
      the H4 signal of the imidazolylethyl moiety. Thus, the imidazolylethyl moiety
      should be located near Trp63 and Ile98, which are in the hydrophobic box most
      proximal to the sugar binding cleft. This situation of the imidazolylethyl moiety
      did not result in steric hindrance to the sugar residue binding at sites B and C.
      The modification affected only the sugar residue binding at site A, and resulted
      in the enhanced activity.

PMID- 7628486
TI  - Cloning and characterization of the human leukotriene A4 hydrolase gene.
AB  - The human gene encoding the bifunctional aminopeptidase and epoxide hydrolase
      enzyme, leukotriene A4 hydrolase (LTA4 hydrolase) has been cloned from a
      placental lambda phage genomic library. The gene is greater than 35 kbp and
      contains 19 exons ranging in size over 24-312 bp. The introns range in size over
      0.26-5.7 kbp. The essential zinc-binding histidine residues and glutamate
      residue, which delineate the zinc-binding domain required for both enzyme
      activities of LTA4 hydrolase, are divided between exons 10 and 11. The LTA4
      hydrolase gene was localized to chromosome 12q22 utilizing fluorescence in situ
      hybridization. Based on the chromosome localization and genomic DNA analysis,
      LTA4 hydrolase was determined to be a single-copy gene. Primer-extension analysis
      demonstrated that the transcription initiation site of LTA4 hydrolase mRNA is 151
      nucleotides upstream of the initiator ATG. Approximately 4 kbp of 5'-flanking
      region of the LTA4 hydrolase gene has been obtained and sequencing of 1.4 kb of
      this 5'-flanking region demonstrated several transcription-factor consensus
      sequences, including a phorbol-ester-response element (AP2) and two xenobiotic
      response elements. The cloning and characterization of the human gene for LTA4
      hydrolase provides a basis for further insight into transcriptional regulation of
      this bifunctional enzyme and its role in various inflammatory processes.

PMID- 7628487
TI  - Characterization of the gene for dbpA, a family member of the nucleic-acid
      binding proteins containing a cold-shock domain.
AB  - Human DNA-binding proteins, dbpA and dbpB (YB-1), are members of a protein family
      containing a cold-shock domain, and are regarded as transcriptional regulators.
      Here, we isolated genomic fragments of these genes and characterized their
      transcriptional regulation. Analysis of lambda phage genomic clones revealed that
      the dbpA gene consists of 10 exons spanning a 24-kb genomic region. The cold
      shock domain, composed of about 70 amino acid residues, is encoded separately by
      exons 2-5. The exon 6, encoding 69 amino acid residues, was found to be an
      alternative exon. Northern-blot analysis showed that both genes were highly
      expressed in skeletal muscle and heart compared with in other tissues. The dbpA
      gene contains no typical TATA box or CAAT box at the immediate 5' region, but a
      sequence similar to an initiator consensus sequence was revealed at a major
      transcription-start site. A transient expression assay using the chloramphenicol
      acetyltransferase reporter gene revealed that the sequence located at positions 
      17 to +70 relative to the major transcription-start site was critical for
      promoter function. Within this region, the consensus sequence for serum-response
      element, CC(A/T)6GG, is present at positions -13 to -4 in addition to the
      initiator sequence. Immunofluorescence showed the cellular localization of dbpA
      to be both in the cytoplasm and nucleus, particularly at the perinuclear region.
      In situ hybridization demonstrated the localization of the dbpA gene on
      chromosome 12 band p13.1, whereas dbpB-(YB-1)-related genes were dispersed on
      many chromosomes with strongest hybridization signals on chromosome 1. All 16
      dbpB (YB-1) clones, isolated from the same genomic library used for dbpA genomic
      cloning, were processed genes because of their intronless structures and multiple
      mutations. One of these processed genes possesses an open reading frame, which
      encodes most of the amino acid residues of dbpB (YB-1). These results indicate
      that dbpA and dbpB (YB-1) genes evolved in different fashions after deviation
      from a common ancestral gene.

PMID- 7628488
TI  - Transcription of immune genes in the giant silkmoth, Hyalophora cecropia, is
      augmented by H2O2 and diminished by thiol reagents.
AB  - Insects have an effective humoral immune system, residing in immune proteins that
      are synthesized largely in the fatbody. kappa B-like motifs upstream of the
      immune protein genes bind the Cecropia immunoresponsive factor (CIF), and confer
      high levels of inducible expression. We have extended our studies and sought
      evidence that oxygen-derived active species might modulate the expression of the
      immune protein genes and the activation of CIF after the administration of
      different inducers. Mitogens, like arachidonic acid, phorbol esters,
      phytohemagglutinin, bacteria, and components of microbial cell envelopes
      stimulate expression of the attacin genes, both in vivo and in vitro. A general
      stimulant of oxidative stress, H2O2, stimulated expression of these genes and the
      weak immune response to wounding was greatly augmented by administration of H2O2.
      These responses were largely or entirely inhibited by dithiothreitol and by N
      acetylcysteine. Nonspecific responses were excluded since immune genes failed to
      respond to albumin or starch, and the expression of a non-immunoresponsive gene
      was not affected. Electrophoretic mobility-shift assays showed that H2O2 and
      bacteria, when administered in vitro, could activate CIF in fatbody cells and
      that dithiothreitol and N-acetylcysteine prevented this process. Our data suggest
      that the induction of the immune protein genes is mediated through the activation
      of CIF, contingent upon thiol oxidation induced by oxidative stress.

PMID- 7628489
TI  - Maize DNA polymerase 2 is a phosphoprotein with increasing activity during
      germination.
AB  - DNA replication is a late event during maize germination and DNA polymerase
      activity increases as germination proceeds. A replicative alpha-type DNA
      polymerase has been purified from maize seeds (DNA polymerase 2) and has been
      shown to be a multisubunit complex [Coello, P., Rodriguez, R., Garcia, E. &
      Vazquez-Ramos, J. M. (1992) Plant Mol. Biol. 20, 1159-1168; Coello, P., Garcia,
      E. & Vazquez-Ramos, J. M. (1994) Can. J. Botany 72, 818-822]. DNA polymerase 2
      activity increased several fold during maize germination, with no apparent change
      in either the amount of holoenzyme or in any of the individual subunits. However,
      the level of phosphorylation of the 90-, 70-, 55- and 45-kDa polypeptides changed
      in a cyclic fashion with their highest levels occurring at 11-14 h and 45-48 h of
      germination. Phosphate incorporated into the different polypeptides in the 11-14
      h period remained stable for at least the next 10 h (to 24 h of germination), the
      period of maximal enzyme activity. However, DNA polymerase 2 processivity was
      very similar in freshly prepared 3-h and 24-h enzymes, and no evidence was found
      that polymerase activity was modified by in vitro phosphorylation. The
      significance of these results is discussed.

PMID- 7628490
TI  - On the legacy of Joseph Babinski.
AB  - Joseph Babinski pioneered development of French neurosurgery and world clinical
      neurology. Although he was best known for his discovery of the extensor plantar
      response, his foundations in the modern semiology of neurology are unequivocal.
      He introduced the concepts and terminology of cerebellar symptoms and discovered
      a reflex asymmetry as the sign of organic disease. Although he considered the
      development of French neurosurgery by his pupils as his greatest accomplishment,
      it is 'the sign' that has dominated his legacy over the years. This sign will
      also celebrate a centenary in 1996.

PMID- 7628492
TI  - Evaluation of outcome of delayed neurologic sequelae after carbon monoxide
      poisoning by technetium-99m hexamethylpropylene amine oxime brain single photon
      emission computed tomography.
AB  - Using brain computed tomography (CT) and single photon emission computed
      tomography (SPECT) with technetium-99m hexamethylpropylene amine oxime (99mTc HM
      PAO) in 13 patients with delayed neurologic sequelae after carbon monoxide
      poisoning, we tried to evaluate the clinical outcome of delayed CO sequelae.
      Among the 13 initial brain CTs, seven showed low density in the cerebral white
      matter and one revealed hypodensity in both globi pallidi. Of the 7 follow-up CT
      scans, 3 have remained unchanged, but in 4 cases more aggravating patterns with
      cortical atrophy without the clinical correlation were observed. There was no
      correlation between the CT findings and the outcome of delayed CO sequelae. All
      initial SPECTs in 13 patients with delayed CO sequelae showed diffuse patchy
      hypoperfusion throughout the cerebral cortex. Among the follow-up SPECTs in 7
      patients, 6 patients showed increased cerebral perfusion with the concomitant
      clinical improvement, but the SPECT of a patient in bedridden state had remained
      unchanged, compared with the initial SPECT. There seemed to be good correlation
      between the findings of SPECT and the outcome of delayed CO sequelae. In
      conclusion, 99mTc HM-PAO brain SPECT is more sensitive than CT, and may be a
      useful test in evaluating the clinical outcome of delayed neurologic sequelae
      after CO poisoning.

PMID- 7628491
TI  - Functional magnetic resonance imaging at 1.5 T during sensorimotor and cognitive
      task.
AB  - Functional activations of the human brain cortex were observed with a standard
      1.5-tesla MR imaging system using a long time echo fast low-angle shot sequence.
      Neural activation increases regional cerebral blood flow resulting in increased
      capillaries and venous blood oxygenation. Processing requires adapted algorithms
      because the time course of intensity signal showed fluctuations of the baseline.
      The use of a 'follow-up' method to generate activation maps is proposed. Brain
      activation was detected in striate cortex during photic stimulation and in
      sensorimotor areas while subjects were moving their hands. In mental imagery
      tasks, we observed a primary and secondary visual cortex activation during memory
      recall of the flashing light. Motor ideation showed an activation of the rolandic
      areas.

PMID- 7628493
TI  - Methylprednisolone infusion during acute exacerbation of MS: plasma and CSF
      concentrations.
AB  - Plasma and CSF concentrations of methylprednisolone (MP), after a high-dose
      intravenous administration (1,500 mg) prescribed to patients presenting acute
      exacerbation of multiple sclerosis, were measured. A plasma pharmacokinetic study
      with 1 CSF sample was performed in 9 patients and 4 other patients had a single
      plasma sample at the time of lumbar puncture. MP plasma kinetics were similar
      between patients. Pharmacokinetic parameters were very close to previous
      published values obtained in normal volunteers or patients with rheumatoid
      disease. Passage of MP into the CSF was delayed since mean plasma/CSF ratio
      dropped dramatically from 150 at the 2nd h to 25 at the 3rd h after starting
      infusion. CSF concentrations of MP were high with a mean reaching 522
      micrograms/l at the 6th h. The high levels of CSF concentrations suggest that MP
      may have powerful pharmacological effects within the CNS. No correlation was
      found between CSF concentration and the clinical response to steroid therapy. The
      issues related to previous data on clinical, biological and radiological effects
      of high-dose intravenous MP are discussed in the light of our results.

PMID- 7628494
TI  - Segmental hyperhidrosis in two siblings with Chiari type I malformation.
AB  - A marked, left-sided segmental hyperhidrosis, verified by quantitative
      evaporimetry, corresponded to an area of dissociated sensory loss in 2 siblings
      (male 49 years old, female 47 years old). MRI scans of the head and whole cord
      demonstrated a Chiari type I malformation in both. In the male, there was a
      syrinx of the neck. The level of this did not correspond to the hyperhidrosis and
      dissociated sensory loss areas of the trunk and thigh. The female, who had no
      syrinx, had hyperhidrosis and dissociated sensory loss of the head, neck, upper
      trunk, and arm, and anisocoria with the larger pupil ipsilateral to the sweating.
      This rare disorder may be due to a disinhibition of the preganglionic sympathetic
      neurons caused by cord lesion(s) interrupting inhibitory descending and spinal
      pathways which are important for the normal thermoregulatory sweating.

PMID- 7628496
TI  - Cerebellar herniation in syringomyelia: relation between tonsillar herniation and
      the dimensions of the syrinx and the remaining spinal cord. A quantitative MRI
      study.
AB  - The dimensions of the syrinx, the remaining spinal cord and the degree of
      cerebellar herniation were analyzed by one- and two-dimensional MRI studies in 22
      patients with syringomyelia. A deep and/or broad cyst tends to be a long one. The
      dimensions of the syrinx and the spinal cord have an inverse relationship. The
      degree of cerebellar herniation is not related to the longitudinal or transverse
      extension of the cyst or the ratio cyst/cord or the remaining spinal cord
      (neither for diameters nor for cross-sectional areas). The dimensions of cysts
      are not significantly greater in patients with tonsillar herniation than in
      patients without. We conclude that cerebellar herniation is not a major
      prognostic factor and should not be overestimated for the development and
      progression of the disease.

PMID- 7628495
TI  - Single photon emission computed tomography using N-isopropyl-p
      [123I]iodoamphetamine in spinocerebellar degeneration.
AB  - We investigated the clinical usefulness of N-isopropyl-p-[123I]iodoamphetamine
      single photon emission computed tomography (SPECT) for diagnosis of
      spinocerebellar degeneration. The uptake in the cerebellar hemispheres and vermis
      was decreased in sporadic cerebelloolivary atrophy (Holmes, n = 9) and sporadic
      olivopontocerebellar atrophy (OPCA, n = 6). The uptake in the pons was decreased
      in OPCA. The decrease of the uptake in the cerebellum and the pons was associated
      with clinical severity in OPCA. Our results show that semiquantitative SPECT
      analysis differentiates between the Holmes type and OPCA.

PMID- 7628497
TI  - The 3243 MELAS mutation in a pedigree with MERRF.
AB  - A mutation at base pair (bp) 3243 in mitochondrial DNA has been associated with
      mitochondrial myopathy, encephalomyopathy, lactic acidosis and stroke-like
      episodes (MELAS). A mutation at bp 8344 has been described as the cause of
      myoclonic epilepsy and ragged-red fiber disease (MERRF). Mitochondrial DNA was
      analyzed in a family with symptoms and signs consistent with MERRF. The DNA
      regions flanking bp 3243 and bp 8344 were amplified using the polymerase chain
      reaction, and the products were digested with restriction enzymes. The MELAS
      mutation at bp 3243 was found, but not the mutation at bp 8344. This illustrates
      the diverse clinical manifestations of the MELAS mutation.

PMID- 7628498
TI  - Late-onset Rasmussen's syndrome with first seizure during pregnancy.

PMID- 7628499
TI  - Cerebral infarction associated with 3,4-methylenedioxymethamphetamine ('Ecstasy')
      abuse.

PMID- 7628500
TI  - Idiopathic hypereosinophilic syndrome with a radiologic pattern of central
      pontine myelinolysis.

PMID- 7628501
TI  - Multimodality evoked potentials and EEG in a case of cherry red spot-myoclonus
      syndrome and alpha-neuraminidase deficiency (sialidosis type 1)

PMID- 7628502
TI  - Chronic inflammatory demyelinating polyneuropathy in patient with rheumatoid
      arthritis.

PMID- 7628503
TI  - Isolated acute urinary retention in herpes simplex infection: selective
      parasympathetic spinal involvement?

PMID- 7628504
TI  - Mitochondrial changes in steroid myopathy with respiratory failure and rapid
      fatal course: report of a case.

PMID- 7628505
TI  - Subclavian steal syndrome in chronic aortic dissection.

PMID- 7628506
TI  - Multiple memory systems in the processing of speech: evidence from aging.
AB  - Young and old adults gave verbatim recall of recorded prose passages that varied
      in average word predictability and rate of presentation. Subjects were allowed to
      interrupt the speech passages at points of their choosing for recall of what they
      had heard on a segment-by-segment basis. For both age groups, the sizes of the
      segments selected were affected by level of predictability but not by the speech
      rate of the spoken passages. Subjects tended to interrupt the passages for recall
      at linguistic constituent boundaries. Recall of the segments was poorer for the
      elderly adults than for the young adults, with larger age differences for faster
      speech rates and for passages that were lower in average word predictability.
      Results are discussed in terms of the recent suggestion that multiple memory
      representations of a speech message may co-occur briefly in time.

PMID- 7628507
TI  - Scope of word meaning activation during sentence processing by young and older
      adults.
AB  - In a naming experiment, we examined word meaning activation on-line during
      sentence processing by younger and older adults. Sentences were biased to either
      the most or least frequently used meaning of a sentence-final ambiguous word. In
      order to determine the scope of initial meaning activation, targets represented
      either high- or low-salient semantic relationships to a single sense of the
      ambiguous word in context. Both age groups evidenced context-dependent activation
      of word meaning. In addition, context activated a wide scope of meaning that
      included both high- and low-salience aspects of the ambiguous words. These
      results contradict predictions based on the inhibition deficit hypothesis (Hasher
      & Zacks, 1988). However, they are compatible with an interactive activation model
      of language comprehension that does not discriminate among age groups.

PMID- 7628508
TI  - Elaborations in adults' text recall: relations to working memory and text recall.
AB  - We examined differences in the elaborative statements produced by younger (mean
      age = 22.19) and older (mean age = 76.56) adults during text recall as well as
      relations between elaborative statements and text recall and working memory.
      Three types of elaborative statements were examined: personal (reactions to a
      text), inferential (inferences derivable about a text), and metacognitive
      (statements concerning understanding or memory of a text). Older adults made more
      personal elaborations during text recall than did younger adults. Younger and
      older adults did not differ in the amount of inferential or metacognitive
      elaborations they made, although all adults made more metacognitive comments when
      texts contained problematic information. Personal elaborations were negatively
      related to recall and accounted for a substantial portion of the age-related
      variance in recall. Personal elaborations were also negatively related to
      processing efficiency, and relations between personal elaborations and working
      memory and storage capacity were mediated by processing efficiency. The results
      are consistent with the view that an age-related increase in non-goal-path
      thoughts, due to inhibitory problems or a different style of text processing, may
      be related to age-related deficits in text processing.

PMID- 7628509
TI  - Age and the ability to inhibit distractor information in visual selective
      attention.
AB  - Adult age differences in the effects of different types of distractor
      interference on visual search were examined. Young adults (mean age = 18.5 years)
      and older adults (mean age = 69.5 years) performed a target-counting task that
      required a complete search of a visual display in each trial. Varying numbers of
      targets were presented alone in displays or were interspersed among eight
      distractor items that were either categorically related (letters) or conceptually
      related (numbers representing either the correct number or the incorrect number
      of targets in the display) to the target item (letter Q). An adult age difference
      in the speed of target enumeration was observed when targets were presented alone
      in the display. In addition, when targets appeared with distractors, both younger
      and older adults were penalized more by conceptually interfering distracters than
      by categorically related distractors. Results did not suggest an age-related
      decline in inhibitory processes.

PMID- 7628510
TI  - Suffix effects and intrusion errors in young and elderly subjects.
AB  - Potential age differences in selective attention and response inhibition in 16
      young and 16 elderly college students were explored using the stimulus suffix
      paradigm. Subjects were presented with auditory and visual lists of seven-letter
      sequences. Half the lists were appended with a letter suffix that was not to be
      recalled. Recall was spoken and written and in strict serial order. Despite
      similar letter spans, serial recall was more difficult for the elderly than for
      the young. Final-item recall advantage in the control condition was reduced more
      for the elderly than for the young in the auditory modality, and the elderly were
      more susceptible to a small degree of visual suffix interference. Older subjects
      made more suffix and extralist intrusion errors than did young subjects. Oral
      recall, along with the method of recording written responses, may have allowed
      these errors to surface. The extralist intrusion errors were phonological or
      based on alphabetic order, suggesting that the elderly may experience task
      competitive, internally generated noise, which enters the response set. The
      suffix intrusions, along with greater susceptibility to the suffix, suggest an
      attentional type of deficit related to ineffective response inhibition in the
      elderly.

PMID- 7628511
TI  - Critical thinking during the adult years: has the developmental function changed
      over the last four decades?
AB  - Age, sex, and education differences in critical thinking during the adult years
      were investigated. The Watson-Glaser (1980) Critical Thinking Appraisal was
      administered to 60 men and women between the ages of 20 and 79. Regression
      analyses indicated that age was significantly related to overall critical
      thinking: Performance decreased with increasing age. Education was also
      significantly related to critical thinking: Performance increased with increasing
      education. However, an interaction between age and education in the analysis of
      total critical thinking scores indicated that education was significantly related
      to critical thinking only in the later adult years. No sex differences were found
      in critical thinking performance.

PMID- 7628512
TI  - Introduction: Normal versus pathological aging: are we screening adequately for
      dementia?

PMID- 7628513
TI  - The sleep apnoea/hypopnoea syndrome.

PMID- 7628514
TI  - The natriuretic peptide family.

PMID- 7628515
TI  - Skeletal muscle and the control of ventilation on exercise: evidence for
      metabolic receptors.
AB  - Patients with chronic heart failure have an increased ventilatory response to
      exercise, and have metabolically abnormal skeletal muscle. It has been proposed
      that a neural signal to ventilation arising from exercising muscle may be
      heightened in chronic heart failure. Our objective was to detect evidence for
      such a signal in normal subjects by studying ventilatory behaviour during
      exercise with muscles in different metabolic states. Fifteen normal subjects
      undertook treadmill exercise both with and without cuffs inflated around each
      thigh to suprasystolic pressure. In a second experiment, a group of 11 normal
      subjects undertook cycle exercise using arms or legs at the same absolute work
      load. Metabolic gas exchange was measured using mass spectrometry with indicator
      gas dilution. The ventilatory response was greater at a given workload when
      subjects exercised with inflated cuffs. Oxygen consumption was reduced in keeping
      with the isolation of the exercising muscle bulk from the circulation. The
      ventilation/carbon dioxide output relationship was described by a linear
      regression function, but the slope of the relationship was increased by 25% from
      20.9 (0.46) to 25.43 (0.73) (P < 0.001). Arm exercise at the same load as leg
      exercise resulted in unchanged oxygen consumption indicating that the same
      external work was being performed. There was an increase in ventilation at a
      given workload. The ventilation/carbon dioxide output slope was increased by 25%
      (from 21.9 (0.9) to 26.3 (0.8)) (P < 0.001). There is a signal to ventilation
      arising from exercising skeletal muscle which is enhanced by the ischaemia
      induced by cuff inflation during exercise. This signal appears to be
      neural.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7628516
TI  - Hydroxylation of collagen type I: evidence that both lysyl and prolyl residues
      are overhydroxylated in osteogenesis imperfecta.
AB  - The composition of the collagens secreted into the media of fibroblast cultures
      of 39 patients with osteogenesis imperfecta (OI) was the same in controls and OI
      cultures. An abnormal migration pattern of collagens upon SDS-PAGE was evident in
      one third of the cultures investigated. Lysyl and prolyl hydroxylation of HPLC
      purified alpha 1(I) chains was elevated in about 60% of cultures. The degree of
      hydroxylation was highest in the lethal forms. The extent of lysyl and prolyl
      hydroxylation showed a strong correlation (r = 0.74, P < 0.001). While high
      levels of hydroxylation are frequently observed in OI patients, a direct
      correlation between lysyl or prolyl hydroxylation and fracture rate or growth
      retardation could not be established.

PMID- 7628517
TI  - Effect of hypertriglyceridaemia on lipoprotein (a) serum concentrations.
AB  - Numerous studies have shown lipoprotein (a) [Lp(a)] serum levels above 0.3 gL-1
      to be a genetically determined and independent risk factor for atherosclerotic
      vascular disease. In this study of sera from 1009 patients attending our lipid
      clinics, multivariate regression analysis revealed an inverse correlation between
      the serum concentrations of triglycerides (TG) and Lp(a) (r = -0.31; P < 0.001)
      as determined by electroimmunodiffusion. This was not observed in 1237 controls
      from a random population. Detailed analysis of the frequency distribution of
      Lp(a) levels at different degrees of hypertriglyceridaemia (HTG) revealed a
      decreasing dosage effect of HTG on Lp(a) serum levels. In 60% of patients with TG
      > 9.12 mmol L-1, this effect led to undetectable serum Lp(a) levels. Dilution of
      hypertriglyceridaemic samples with normotriglyceridaemic sera containing high
      levels of Lp(a) revealed that analytical interference in part accounts for the
      decreasing effect of TG-rich lipoproteins on Lp(a). Re-evaluation of 45
      hypertriglyceridaemic samples by enzyme immunoassay and immunoblotting revealed
      the presence of small amounts of Lp(a) in several samples which were considered
      to be free of Lp(a) upon electroimmunodiffusion. We conclude that TG-rich
      lipoproteins interfere with the quantification of Lp(a), at least by
      electroimmunodiffusion. However, HTG may also decrease Lp(a) plasma
      concentrations in vivo, possibly by increased clearance of TG-rich Lp(a).

PMID- 7628518
TI  - Transforming growth factor beta 1 modulates angiotensin II-induced calcium influx
      in vascular smooth muscle.
AB  - The modulatory effects of transforming growth factor beta 1 (TGF beta 1) on the
      angiotensin II (Ang II)-induced increase in cytosolic free calcium concentration
      ([Ca2+]i) were investigated in vascular smooth muscle cells (VSMC) from
      spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY).
      [Ca2+]i in VSMC was measured using the fluorescent dye fura-2. When TGF beta 1
      was applied 30s prior to Ang II, the Ang II-induced [Ca2+]i increase was
      significantly enhanced in VSMC from SHR (P < 0.05 compared to control), whereas
      after the preincubation with TGF beta 1 for 30 min, the Ang II-induced [Ca2+]i
      increase was significantly reduced in VSMC from both strains. Using the manganese
      quenching technique, it was confirmed that short-term exposure to TGF beta 1
      enhanced the Ang II-induced trans-plasma-membrane calcium influx in SHR. The
      inhibition of protein kinase C by calphostin C abolished the stimulatory effect
      of TGF beta 1 on the Ang II-induced [Ca2+]i increase. It is concluded that TGF
      beta 1 modulates the Ang II-induced calcium handling in VSMC.

PMID- 7628519
TI  - Severe hypercholesterolaemia: unusual inheritance in an Italian pedigree.
AB  - A family presenting several cases of severe primary hypercholesterolaemia and/or
      premature sudden death was studied. This family is characterized by
      consanguinity, absence of vertical transmission, bimodal distribution of plasma
      cholesterol values, and reduction of reproductive fitness in affected
      individuals. The probands have clinical traits of homozygous familial
      hypercholesterolaemia, including hypercholesterolaemia, xanthomas and early
      coronary atherosclerosis, while the parents and grandparents are clinically
      normal. Eight relatives on the mother's side experienced premature sudden death,
      and in four cases hypercholesterolaemia was diagnosed. Haplotype segregation
      analysis of the inheritance of the LDL receptor and apo B genes in the probands'
      family excluded the involvement of these two genes in the pathogenesis of the
      disease. LDL receptor activity, as well as the ability of LDL to bind to the LDL
      receptor, and plasma vegetal sterols were within normal limits both in probands
      and in their relatives. The study of this pedigree suggests that
      hypercholesterolaemia is not produced by defects in the LDL receptor or LDL
      particles, and disease inheritance is consistent with an autosomal recessive
      trait.

PMID- 7628520
TI  - Decreased affinity of low density lipoprotein (LDL) particles for LDL receptors
      in patients with cholesteryl ester transfer protein deficiency.
AB  - We have reported that the disorder of lipoprotein metabolism in
      hyperalphalipoproteinaemic patients with a deficiency of cholesteryl ester
      transfer protein (CETP) is characterized by the polydisperse low density
      lipoprotein (LDL) particles and the accumulation of cholesteryl ester (CE) in
      high density lipoprotein (HDL) particles, forming cholesterol-induced HDL (HDLc)
      like particles. In the present study we have investigated the interaction of
      these abnormal LDL with LDL receptors of normal human fibroblasts. Since the
      ultracentrifugally separated LDL fraction (1.019 < d < 1.063 g mL-1) from the
      CETP-deficient patients contained HDLc-like particles, these particles were
      removed by anti-apolipoprotein (apo) A-I immunoaffinity column chromatography.
      The lipoproteins eluted in the unbound fraction of this column did not contain
      apo A-I, so this fraction was considered to be authentic LDL. The authentic LDL
      of the patients were deficient in CE and rich in triglycerides and apo B. The
      authentic LDL itself showed polydispersity, ranging in size from 23 nm to 30 nm.
      The affinity of these abnormal LDL particles for LDL receptors was analysed by a
      competitive assay in which cold LDL from the patients or control compete with
      125I-labelled LDL for fibroblast LDL receptors. The concentration of LDL
      particles at which 50% of 125I-labelled normal LDL was replaced was two to three
      times higher for the patients than for the normal control. Therefore, the
      affinity of patient LDL was thought to be reduced compared to that of control
      LDL. These results demonstrate that CETP may play an important role in making LDL
      particles homogeneous and rich in CE.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7628521
TI  - PC:PS liposomes induce a recruitment of neutrophils and the release of TNF alpha
      in the lungs of mice sensitized with Saccharopolyspora rectivirgula.
AB  - The aim of this study was to verify the effect of nasally instilled liposomes (L)
      or dexamethasone-containing L (Ldexa) on normal or inflamed lung tissue. Three
      groups of mice were studied. Group I was given saline instillations for 3 weeks
      prior to the instillation with liposomes. In groups II and III lung inflammation
      was induced by repeated instillations of Saccharopolyspora rectivirgula before
      the instillation of liposomes (group II) or liposomes containing dexamethasone
      (group III). Animals from all groups were killed at regular time intervals for up
      to 48 h after the instillation of liposomes. The total cell count in
      bronchoalveolar lavage fluid did not differ significantly between groups I and
      II. However, in group III it decreased rapidly from 6.2 to 2.8 x 10(5) cells mL-1
      within 2 h. Differential counts did not change in group I, but in group II a
      transient neutrophilia was observed 180 min after the instillation of liposomes.
      In group III, the instillation of dexamethasone-containing liposomes depleted all
      neutrophils and lymphocytes after 4 h. No TNF alpha was found in samples of
      lavage fluid from any of the groups at time 0. In group I, liposomes induced the
      production of 0.03 ng mL-1 of TNF alpha in the 1 h sample only. In group II, TNF
      alpha peaked to 1 ng mL-1 at 1 h and had decreased to 0.35 ng mL-1 by 3 h. In
      group III, TNF alpha peaked at 1 h, but only reached a level of 0.1 ng mL
      1.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7628522
TI  - The influence of local skin heating and reactive hyperaemia on skin blood flow
      abnormalities in patients with reflex sympathetic dystrophy (RSD).
AB  - Skin blood flow in reflex sympathetic dystrophy (RSD) patients has been reported
      to develop from an increase at an early stage to a decrease at later stages. So
      far, it remains unclear whether these abnormalities are solely of
      microcirculatory origin, and result from functional vasospasm or structural
      vessel wall changes. Eighty-seven RSD patients were categorized as follows: stage
      I in case of a stationary warmth sensation; stage II in case of an intermittent
      warmth and cold sensation; and stage III in case of a stationary cold sensation.
      Laser Doppler flowmetry (LDF) was used as a measure of total skin blood flow and
      transcutaneous oximetry (TCPO2) as a measure of vascular reactivity in the more
      superficial skin layers. Local skin heating and reactive hyperaemia were used to
      study the relative reserve capacity of skin microvessels. Finapres was used to
      assess digital arterial pressures. As compared to healthy volunteers (n = 16),
      LDF under control conditions demonstrated an increase in skin blood flow at stage
      I (P < 0.01). A decrease in skin blood flow under control conditions was seen at
      stages II (P < 0.05) and III (P < 0.05), but the relative flow reserve capacity,
      as measured with LDF, was not impaired at these stages. Regression analysis did
      not show a relation between LDF parameters and duration of the syndrome. TCPO2
      revealed no differences between patient groups and controls. Regression analysis
      did not demonstrate a relation between TCPO2 parameters and duration of the
      syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7628523
TI  - Diagnostic value of C-reactive protein measurement does not justify replacement
      of the erythrocyte sedimentation rate in daily general practice.
AB  - The purpose of this paper was to establish the diagnostic value of the C-reactive
      protein measurement (CRP) in patients attending their general practitioner (GP)
      with a new complaint for which the GP considers determination of the erythrocyte
      sedimentation rate (ESR) to be indicated. During 4 successive months in 1992, 11
      GPs in four general practice centres in the Netherlands identified patients
      indicated for the erythrocyte sedimentation rate. ESR and CRP were determined at
      the local hospital laboratory. One year later, an independent GP established the
      follow-up diagnoses. By comparing the test results with the follow-up diagnoses,
      using logistic regression analysis and Receiver Operating Characteristic curves,
      sensitivities, specificities, predictive values and odds ratios were established.
      In 396 patients the prevalence of inflammatory diseases and malignancies
      ('pathology') was found to be 26% in males and 15% in females. Both ESR and CRP
      were valuable in discriminating pathology from harmless, often self-limiting
      diseases. The optimal upper limits of reference values ('cut-off points') for ESR
      were found to be 31 mm in both males and females. At these cut-off points, the
      diagnostic gains from positive and negative test results (positive predictive
      value minus prevalence, and negative predictive value minus 100% minus
      prevalence) were 45% and 4% for males and 30% and 2% for females. The optimal cut
      off point for CRP was found at 15 mg L-1 in males and 34 mg L-1 in females. The
      diagnostic gain from positive and negative test results were 18% and 9% in males
      and 25% and 4% in females.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7628524
TI  - Surgical removal of insulinoma restores glucose recovery from hypoglycaemia but
      does not normalize insulin action.
AB  - In the present study we have evaluated the effects of chronic hyperinsulinaemia
      secondary to insulinoma, on insulin sensitivity and on counter-regulatory
      responses to hypoglycaemia. We studied six patients (M/F = 3/3; age = 40 +/-
      years), before and 6-9 months after surgical ablation of the neoplasia, by means
      of an euglycaemic-hyperinsulinaemic clamp (1 mU kg-1 min-1). Seven normal
      subjects (M/F = 4/3; age = 38 +/- 6 years) underwent the same experimental study
      as the control subjects. In insulinoma patients after 100 min of the euglycaemic
      hyperinsulinaemic clamp, glycaemia was allowed to drop to a minimum value of 1.9
      mmol L-1, and recovery evaluated after interrupting insulin infusion. During the
      entire study, 3-3H-glucose was infused to determine hepatic glucose production
      and glucose utilization. Surgical removal of the pancreatic adenoma was followed
      by a reduction in body weight (BMI = 25.7 +/- 1.9 vs. 23.0 +/- 1.6 kg m-2; P <
      0.05), normalization of fasting plasma levels of glucose (2.94 +/- 0.16 vs. 4.83
      +/- 0.11 mmol L-1), insulin (162 +/- 24 vs. 48 +/- 12 pmol L-1) and of basal
      hepatic glucose production (7.6 +/- 0.7 vs. 12.2 +/- 1.11 mumol kg-1 min-1).
      Before the operation, insulin-mediated glucose disposal was significantly lower
      than in the controls (30.8 +/- 3.1 vs. 49.1 +/- 3.1 mumol kg-1 min-1). Six to
      nine months after surgical removal of the adenoma, glucose utilization was
      unchanged (30.5 +/- 3.3 mumol kg-1 min-1) and still significantly lower than in
      controls (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7628525
TI  - High lipoprotein(a) levels with predominance of high molecular weight apo(a)
      isoforms in patients with pulmonary embolism.
AB  - Lipoprotein(a) (Lp(a)) may interact with the cellular components and protein co
      factors of fibrinolysis. To evaluate the effect of Lp(a) in thromboembolic
      diseases of the venous system, we measured serum levels and the isoform
      distribution of apo(a) in 25 patients with pulmonary embolism (18 men, 7 women,
      aged 21-77 years). The control group was adjusted for sex and age (P = 0.189).
      Serum Lp(a) concentration was significantly higher in the study group (median:
      9.3 vs. 4.3 mg dL-1). As the distribution of high and low molecular weight
      subtypes of apo(a) did not show any differences (P = 0.127) between the two
      groups, the elevated Lp(a) levels in patients with pulmonary embolism could not
      be attributed to the investigated kringle-4 polymorphism of the apo(a) gene and
      therefore other genetic or non-genetic implications are indicated.

PMID- 7628526
TI  - Nuclear-cytoplasmic translocations of protein p26 during aerobic-anoxic
      transitions in embryos of Artemia franciscana.
AB  - Embryos of the crustacean Artemia franciscana survive continuous anoxia for
      periods of years, during which their metabolism comes to a reversible stand
      still. A question of some interest concerns the maintenance of cellular integrity
      in the absence of biosynthesis and an ongoing energy metabolism. The present
      paper continues previous work on an abundant protein (p26) that undergoes
      extensive intracellular translocation during aerobic-anoxic transitions, exhibits
      several characteristics of stress proteins, and might be involved in metabolic
      regulation during aerobic-anoxic transitions. Since it has been established that
      intracellular pH (pHi) plays a major role in aerobic-anoxic transitions in this
      system we examined the pH-dependence of nuclear-cytoplasmic translocations of
      p26. In unincubated and aerobic-incubated embryos (pHi > or = 7.9) p26 was
      located in the "soluble" fraction, whereas in anoxic embryos (pH about 6.3)
      roughly 50% was translocated into the nucleus as shown by immunocolloidal gold
      electron microscopy. These nuclear translocations also took place in vitro,
      simply by manipulating buffer pH in a physiologically appropriate fashion.
      Immunostaining of Western blots prepared after two-dimensional electrophoresis
      revealed several isoforms of native p26. The isoelectric point of the major
      isoform was 7.10 +/- 0.05, a value close to the pH at which p26 translocation
      into the nucleus was first initiated in vitro. 31P-NMR measurements indicated
      that pHi was maintained at acidic levels (about 6.3) during prolonged anoxia. We
      also found that pHi of hydrated (0 degree C) but otherwise unincubated embryos
      was alkaline, allowing for rapid resumption of metabolism under permissive
      conditions. The significance of these pH-dependent translocations of p26 is
      discussed.

PMID- 7628527
TI  - Programmed cell death and expression of the protooncogene bcl-2 in myocytes
      during postnatal maturation of the heart.
AB  - To determine whether programmed myocyte cell death is a major component of the
      differential growth adaptation of the right and left ventricle during
      development, the formation of DNA strand breaks in myocyte nuclei was identified
      and quantitated in hearts of rats at the end of gestation and at 1, 5, 11, and 21
      days after birth. Incorporation of BrdU in left and right ventricular myocytes
      was also evaluated. Moreover, the expression of bcl-2 in myocytes was determined.
      Programmed myocyte cell death was absent in the fetal heart but affected the
      myocardium postnatally. This phenomenon was no longer detectable at 21 days. DNA
      strand breaks in nonmyocyte nuclei were present at all time intervals.
      Quantitatively, 10.4, 6.1, and 2.5 myocyte nuclei/10,000 nuclei exhibited DNA
      degradation at 1 day in the right ventricle, interventricular septum, and left
      ventricule, respectively. Corresponding values at 5 days were 3.7, 3.5, and 2.0
      myocyte nuclei/10,000 nuclei. At 11 days, programmed cell death involved 1.2,
      1.5, and 0.53 myocyte nuclei/10,000 nuclei in these three regions of the heart.
      The 4.2-fold, 1.9-fold, and 2.3-fold greater magnitude of programmed cell death
      in the right ventricle at 1, 5, and 11 days was statistically significant. In
      contrast, BrdU incorporation in myocytes decreased in a comparable manner in the
      left and right ventricles with maturation. Importantly, bcl-2 mRNA levels were
      high in fetal myocytes, decreased markedly at 1 and 5 days, and progressively
      increased at 11 and 21 days. The expression of bcl-2 was lower in right than in
      left ventricular myocytes. In conclusion, programmed myocyte cell death is
      inversely related to bcl-2 expression and affects the right ventricle more than
      the left ventricle during postnatal development. This phenomenon may be crucial
      in the modulation of the number of myocytes in the two ventricles during the
      transition from the fetal to the adult circulatory system.

PMID- 7628528
TI  - The post-transcriptional regulator Rex of the human T-cell leukemia virus type I
      is present as nucleolar speckles in infected cells.
AB  - The rex-encoded protein (Rex) of human T-cell leukemia virus type I (HTLV-I) is
      responsible for the cytoplasmic accumulation of incompletely spliced mRNAs that
      encode the virion structural proteins. Rex is known to be located predominantly
      in the cell nucleoli in transient transfections or in the isolated nuclei of HTLV
      I-infected cells. However, precise location of Rex under physiological conditions
      has not been determined unequivocally. Here we report that Rex is primarily
      located as intranucleolar speckles in HTLV-I-infected cells, except for a few
      nucleoplasmic speckles. This is in contrast to the more diffuse nucleolar
      distribution of the rev-encoded protein (Rev) of human immunodeficiency virus
      type 1 (HIV-1), the functional homologue to Rex, in HIV-1-infected cells.
      Accumulation of Rev is associated with disruption of nucleolar structure and cell
      death, whereas Rex does not have these effects. The difference in distribution of
      Rex and Rev within the nucleoli may reflect the difference of toxicity toward the
      host cells. Involvement of the nucleolus in processing of certain mRNAs is also
      discussed.

PMID- 7628529
TI  - Evidence for a critical telomere length in senescent human fibroblasts.
AB  - Telomeres, the G/C-rich DNA sequences capping the ends of all eukaryotic
      chromosomes, have been shown to shorten during replicative aging of normal cells
      in vitro and in vivo. Moreover, variation in the initial length of terminal
      restriction fragments (TRF) accounts for much of the variation in replicative
      capacity of fibroblast cultures from different donors. Since replicative capacity
      also varies significantly between clones in a mass culture of fibroblasts from a
      single donor, we wished to further test the hypothesis that the shortening of
      telomeres to a critical or threshold length acts as a signal for cell senescence.
      Thus, we measured TRF length and total telomeric signal intensity for 35 clonal
      fibroblast populations at early passage and at senescence. Replicative capacity
      was found to be directly proportional to mean TRF length (m = 7.2 population
      doublings/kbp, r = 0.65, P = 0.0004) and total signal intensity (m = 25.0
      population doublings/unit, r = 0.63, P < 0.003) at early passage. More
      importantly, the variability in both mean TRF length and signal intensity (F =
      2.0 and 2.9; P = 0.02 and 0.03, respectively) at senescence was markedly less
      than that at early passage. Although initial telomere length cannot account for
      all of the interclonal variability in replicative capacity, our observations
      support the existence of a critical telomere length in senescing cells and a
      causal role of telomere shortening in cell senescence.

PMID- 7628530
TI  - Translocation of ferritin and biomineralization of goethite in the radula of the
      limpet Cellana toreuma reeve.
AB  - The radula of the limpet, Cellana toreuma, consists of a continuous series of
      teeth in various stages of iron biomineralization. The major iron-binding protein
      of the limpet's iron-containing granule (siderosome) has been purified and
      identified as ferritin. Limpet ferritin has a M(r) of 575 kDa and can be resolved
      into two bands by SDS-PAGE analysis, with respective M(r)s of 26 and 21 kDa. The
      partial N-terminal amino acid sequences of these two subunits were confirmed, and
      antisera against them were respectively generated. The specifity of these two
      antisera shows no difference between them. By using transmission electron
      microscopy and immunogold staining techniques the following two events were
      revealed: (1) in the superior epithelial cell of the radula, ferritin was
      disassembled through autophagy or heterophagy before exocytosis; (2) of the
      limpet ferritin, at least the 26-kDa subunit was found to pass through the
      microvilli, resulting in the accumulation of iron in the extracellular tooth
      chamber and the formation of goethite needles. Intracellular ferritin being
      translocated to the extracellular environment is discussed in the text.

PMID- 7628531
TI  - Expression of intercellular adhesion molecule-1 is regulated by the actin network
      in epidermoid carcinoma cells.
AB  - Expression of the cell surface protein intercellular adhesion molecule-1 (ICAM-1)
      is a prerequisite for the interaction of a large variety of cells with
      leukocytes. Constitutive expression of ICAM-1 in human epidermoid carcinoma cells
      is low, but is inducible through inflammatory cytokines including interferon
      gamma (INF gamma). Disruption of the actin cytoskeleton with dehydrocytochalasin
      B (CB) increased constitutive and potentiated INF gamma-induced ICAM-1 cell
      surface expression, but did not alter formation of soluble ICAM-1. Actinomycin D
      inhibited CB-induced ICAM-1 surface expression and CB increased the steady-state
      levels of ICAM-1 transcripts. However, CB did not alter the glyceralaldehyde-3
      phosphate dehydrogenase mRNA levels and the ICAM-1 mRNA half-life. These studies
      indicate that in human epidermoid carcinoma cells the actin cytoskeleton
      regulates ICAM-1 transcription and cell surface expression.

PMID- 7628533
TI  - Extracellular matrix, growth factors, genetics: their influence on cell
      proliferation and myotube formation in primary cultures of adult mouse skeletal
      muscle.
AB  - Cell proliferation and myotube formation in response to growth factors on various
      extracellular matrices (ECM) were investigated in primary skeletal muscle
      cultures from adult SJL/J and BALB/c mice. There was no difference between the
      rates of proliferation from primary cultures of SJL/J and Balb/c mice measured at
      48 h in response to a range of concentrations of PDGF-AA, -AB, -BB, TGF beta 1,
      or LIF (added at 24 h). SJL/J primary cultures were more responsive to bFGF
      (which was the most potent mitogen) than were BALB/c cultures. Comparison of dose
      response curves to bFGF and TGF beta 1 grown on gelatin or Matrigel showed that
      the nature of the ECM did not have a significant affect. More myotubes formed at
      4 days in SJL/J than in parallel BALB/c cultures on gelatin or Matrigel (P <
      0.05). On gelatin more myotubes with 4 or more nuclei were formed in cultures
      from SJL/J than BALB/c muscles (P < 0.05); however, on Matrigel these myotubes
      occurred with similar frequency. Myotube formation examined in BALB/c muscle
      cultures grown on collagen i.v., entactin-free laminin, and fibronectin showed
      that none of these ECM components alone supported large myotube formation (4 or
      more nuclei) as well as did Matrigel, although fibronectin was as effective as
      Matrigel with respect to the total number of myotubes formed. Parallel
      experiments carried out using the myogenic H-2Kb(27) cell line showed similar
      effects with the exception of laminin which enhanced large myotube formation and
      desmin expression in the H-2Kb(27) but not in the primary muscle cultures. The
      greater sensitivity in mitogenic response to bFGF and the more extensive myotube
      formation seen in SJL/J compared with BALB/c cultures in vitro reflects the
      superior capacity for muscle regeneration of SJL/J mice in vivo.

PMID- 7628532
TI  - Dissociation of nuclear and cytoplasmic cell cycle progression by drugs employed
      in cell synchronization.
AB  - We have studied the effect of the cell synchronization agents compactin,
      ciclopirox olamine, mimosine, aphidicolin, ALLN, and colcemid on several
      parameters of cell cycle progression in mitotically synchronized HeLa S3 cells.
      Using cell size and cyclin A and B levels as markers of cytoplasmic progression
      and DNA content as a measure of nuclear cell cycle position, we have examined
      coordination of cytoplasmic and nuclear events during induction synchrony. Each
      synchronizing agent was unique in its effect on the coordination of the
      cytoplasmic and nuclear cycle. Mimosine, aphidicolin, ALLN, and colcemid
      disrupted cell cycle integration while compactin and ciclopirox olamine did not.
      Continued net cell growth during cell cycle arrest was the most dramatic in
      aphidicolin-treated cells, which averaged a 60% increase in size. Mimosine, ALLN,
      and colcemid produced an increase in cell size of approximately 25%, and
      ciclopyrox olamine and compactin exerted a negligible effect. Cyclin A and B were
      found at mitotic (high) or G1 (low) levels, or in combination of high and low
      concentrations not correlated with DNA content in drug-treated cells. For
      example, treatment with mimosine, which arrests cells in G1 with 2C DNA, resulted
      in cyclin A accumulating to mitotic levels, whereas cyclin B remained at a low
      concentration, the first time this phenomenon has been observed. These results
      demonstrate that populations of synchronized cells obtained by different drug
      treatments are blocked at biochemically distinct cell cycle points not apparent
      by cytometric measurement of DNA content. Our results provide conclusive evidence
      that induced synchrony methods differ with respect to their impact on cell cycle
      organization and from the pattern seen with nonperturbing cell selection methods.

PMID- 7628534
TI  - Subcellular localization of moesin in dynamic filopodia, retraction fibers, and
      other structures involved in substrate exploration, attachment, and cell-cell
      contacts.
AB  - Moesin, a member of the talin-4.1 superfamily, is a linking protein of the
      submembraneous cytoskeleton. It is expressed in variable amounts in cells of
      different phenotypes such as macrophages, lymphocytes, fibroblastic, endothelial,
      epithelial, and neuronal cell lines. In this report we show that moesin is not
      randomly distributed throughout the cortical cytoskeleton, but rather that it is
      concentrated in specialized microdomains. It is localized in the intracellular
      core of microextensions known as filopodia, microvilli, microspikes, and
      retraction fibers. This subcellular distribution follows closely the dynamic
      changes in cell shape that take place when cells attach, spread, and move
      spontaneously or in response to extracellular signals. This suggests a similar
      function for moesin in diverse cell types related to the dynamic restructuring of
      domains of the plasma membrane and underlying membrane skeleton. Support for this
      comes from studies on PC-12 cells, which respond to NGF by extending neurites and
      moesin is redistributed from a diffuse localization to growth cone filopodia. In
      fibroblastic (NIH3T3) or macrophage (RAW264.7) cell lines, moesin is found in
      filopodia appearing at random on the cell surface soon after the cells are placed
      in culture, begin to attach, and spread. In polarized epithelial cells (LLC-PK1),
      moesin is associated with peripheral filopodia and apical microvilli. The
      cellular microextensions containing moesin are devoid of microtubules, focal
      contact proteins such as vinculin, and cortical cytoskeletal elements such as
      protein 4.1, but they do contain varying amounts of actin microfilaments. This
      localization of moesin in microextensions is not influenced by cytochalasin B.
      Treatment of cells with phorbolester (PMA) causes rapid cell spreading,
      disappearance of filopodia and retraction fibers, and moesin does not accumulate
      in the actin-rich lamellae that form at the cellular edges. After removal of PMA,
      cells retract and moesin again becomes concentrated in filopodia and retraction
      fibers. These studies support the hypothesis that filopodia, retraction fibers,
      and other microextensions of the plasma membrane are unique cellular microdomains
      with characteristic submembraneous components. Moesin could be involved in the
      dynamic restructuring of such microdomains by regulating binding interactions
      between the plasma membrane and the actin cytoskeleton.

PMID- 7628535
TI  - Modulation of hepatocyte growth factor and c-met in the rat mammary gland during
      pregnancy, lactation, and involution.
AB  - Epithelial tubulogenesis is responsible for the exquisitely intricate
      organization of functional units of parenchymal organs. We have previously
      demonstrated that hepatocyte growth factor (HGF--also known as scatter factor) is
      a stroma-derived epithelial morphogen, which induces tubulogenesis by kidney
      derived epithelial cells in vitro. The mammary gland provides a particularly
      attractive model for the study of epithelial morphogenesis, since its development
      in postnatal life involves elongation and branching of epithelial tubules. The
      aim of the present studies was to assess the expression and modulation of HGF and
      its receptor c-Met in the rat mammary gland during pregnancy, lactation, and
      involution. By ribonuclease protection assay, we demonstrate that levels of both
      HGF and c-met transcripts are progressively reduced during pregnancy, are
      virtually undetectable during lactation, and increase during the phase of
      involution to prepregnancy levels. The reduction in HGF and c-met expression
      corresponds to periods in which functions other than tubulogenesis predominate in
      the mammary gland, namely alveologenesis (mid to late pregnancy) and milk protein
      synthesis (lactation). Using a murine mammary gland-derived epithelial cell line,
      we demonstrate that levels of c-met mRNA are significantly reduced by exogenously
      added prolactin, providing a possible explanation for the reduction in c-met in
      the rat mammary gland during lactation. The potential significance of down
      regulation of HGF/c-met during lactation is discussed.

PMID- 7628536
TI  - A chemically defined medium supports in vitro proliferation and maintains the
      osteochondral potential of rat marrow-derived mesenchymal stem cells.
AB  - Among the stromal elements in mammalian and avian bone marrow there exists a
      pluripotent subset of cells which we refer to as mesenchymal stem cells (MSCs).
      These cells can be isolated and will proliferate in culture. When such
      subcultured cells are introduced into porous tricalcium phosphate-hydroxyapatite
      ceramic cubes and implanted subcutaneously into syngeneic or immunocompromised
      hosts, the passaged MSCs are observed to differentiate into bone and cartilage.
      Heretofore, those assays have been conducted with MSCs which had been maintained
      in vitro in serum-containing medium. A serum-free medium (RDM-F), which consists
      of insulin, 5 micrograms/ml, linoleic acid-bovine serum albumin, 0.1%, platelet
      derived growth factor-BB, 10 ng/ml, and basic fibroblast growth factor, 1 ng/ml
      in a base medium of 60% Dulbecco's modified Eagle's medium with low glucose and
      40% MCDB-201, has been developed for rat marrow-derived MSCs. Proliferation rates
      of MSCs maintained in RDM-F equal those of cells maintained in serum-containing
      medium through Day 4 following subculturing and continue at up to 80% of the rate
      of the latter through Day 8 of subculture. When tested in the in vivo ceramic
      cube assay, MSCs cultured in RDM-F retain their osteochondral potential and
      differentiate into bone and cartilage in a manner indistinguishable from those
      cultivated in serum-containing medium. Utilization of this serum-free medium will
      facilitate analysis of the effects of other growth factors and cytokines on the
      proliferation and differentiation of MSCs, without the complexity of exogenous
      serum.

PMID- 7628538
TI  - The alpha 3 beta 1 integrin is involved in melanoma cell migration and invasion.
AB  - The VLA3 (alpha 3 beta 1) integrin receptor recognizes several ligands; however,
      the function of this integrin is still debated. Expression of VLA3 appears to be
      increased in malignant melanoma and correlates with the degree of dermal
      invasiveness. Here we have studied the role the alpha 3 integrin subunit in
      malignant melanoma cell migration and invasion into extracellular matrices. The
      2/14 clone of the Me665/2 human melanoma cell line, which expresses high levels
      of VLA integrins, was highly migratory and invasive, while the low integrin
      expressing 2/56 clone showed limited migration and was not invasive. Antibodies
      to the beta 1 subunit inhibited adhesion, migration, and invasion of two
      different malignant melanoma cell lines, the 2/14 clone and A2058 cells,
      indicating a crucial role for VLA integrins in these phenomena. While anti-alpha
      6 antibodies inhibited adhesion to laminin and anti-alpha 5 antibodies inhibited
      adhesion to fibronectin, antibodies to the alpha 3 subunit did not inhibit
      adhesion of these cells to laminin, fibronectin, or collagen i.v. In contrast,
      the P1B5 anti-alpha 3 antibodies were good inhibitors of the migration of these
      cells toward laminin, fibronectin, and collagen IV and also blocked invasion of
      these cells through a reconstituted basement membrane matrix (Matrigel). Another
      anti-alpha 3 antibody, F4, did not effect migration, while both the P1B5 and F4
      antibodies induced cellular aggregation on Matrigel. Our data suggest a specific
      role for alpha 3 beta 1 in the migration and invasion of melanoma cells.

PMID- 7628537
TI  - Interruption of myogenesis by transforming growth factor beta 1 or EGTA inhibits
      expression and activity of the myogenic-associated (2'-5') oligoadenylate
      synthetase and PKR.
AB  - Interferon-induced proteins have been previously implicated in the regulation of
      cell growth. In an attempt to provide evidence for the involvement of these
      proteins in differentiation, the effect of transforming growth factor beta 1 (TGF
      beta) and EGTA on the expression and activity of (2'-5') oligoadenylate
      synthetase (2-5A synthetase) and double-stranded RNA activated protein kinase
      (PKR) during myogenesis of rat primary skeletal muscle cultures or the myogenic
      cell line L8 was studied. Both TGF-beta and EGTA inhibited the fusion of
      myoblasts and reduced significantly the level of the muscle-specific proteins,
      acetylcholine receptors, and creatine kinase activity in rat primary muscle
      cultures. Likewise, TGF-beta exhibited a similar inhibitory effect on the fusion
      of L8 cells and the level of creatine kinase activity in these cells. The
      kinetics of 2-5A synthetase activity in both types of cells during
      differentiation was then established. In both types, a transient increase in
      activity was observed followed by a decrease thereafter. However, while the peak
      activity in primary muscle cultures appeared after 24 h in culture, it was
      observed only on the third day in L8 cells grown in differentiation medium (DM).
      Treatment of primary cultures with either TGF-beta or EGTA reduced the amount of
      1.7-kb 2-5A synthetase-specific RNA transcripts and decreased significantly the
      level of 2-5A synthetase activity compared to that in untreated cultures. Western
      blot analysis of 2-5A synthetase proteins in untreated primary muscle cultures
      showed that the major species synthesized in these cells was the 43-kDa isoform
      of the enzyme. However, the 71-kDa isoform was clearly visible after 72 h in
      culture. Both TGF-beta and EGTA abrogated the appearance of all forms of 2-5A
      synthetase. Similarly, in L8 cells grown in DM, TGF-beta down-regulated the
      expression of 2-5A synthetase and reduced the level of enzymatic activity.
      Western blot analysis revealed the presence of the 71-kDa isoform as the major
      species of 2-5A synthetase in L8 cells; however, the 43-kDa isoform was also
      visible on the third day in DM. TGF-beta treatment resulted in a reduced amount
      of 2-5A synthetase proteins. The kinetics of PKR activity in L8 cells grown in DM
      was similar to that observed with 2-5A synthetase. Furthermore, TGF-beta strongly
      reduced the level of PKR activity in differentiating L8 cells.

PMID- 7628540
TI  - Identification of integrins involved in cell adhesion to native and denatured
      type I collagens and the phenotypic transition of rabbit arterial smooth muscle
      cells.
AB  - Rabbit smooth muscle cells (SMC) in primary culture attached to and started
      proliferating on native and heat-denatured type I collagens, although the amount
      of cell attachment to denatured collagen was significantly lower. The cells
      adhered poorly and were unable to grow on commercial gelatin. In contrast,
      synthetic SMC in secondary culture could adhere to gelatin and grew as well on
      gelatin as on native type I collagen. The SMC in the contractile state adhered to
      native type I collagen through the alpha 1 beta 1 and alpha 3 beta 1 integrins.
      The cells in the intermediate phenotype also adhered to the substrate through the
      alpha 1 beta 1 and alpha 3 beta 1 integrins, but the relative amount of alpha 3
      integrin decreased. The initial adhesion of cells in secondary culture to native
      type I collagen was mediated only by the alpha 1 beta 1 integrin. The cell
      binding sequences did not contain DGEA (Asp-Gly-Glu-Ala) or RGD (Arg-Gly-Asp). In
      contrast, cell adhesion to heat-denatured type I collagen was mediated only by
      the alpha 1 beta 1 integrin in the contractile state and by the alpha 1 beta 1,
      alpha 2 beta 1, and alpha 3 beta 1 integrins in the synthetic state. In heat
      denatured type I collagen, the sequences DGEA and RGD served as a recognition
      site for the alpha 2 beta 1 and alpha 3 beta 1 integrins. Our results suggest
      that rabbit SMC can recognize the native and denatured type I collagens through
      interactions with the triple helix-binding receptors and alpha chain-binding
      receptors and that the expression pattern of integrins changes in conjunction
      with the phenotypic properties of vascular SMC.

PMID- 7628539
TI  - Effect of cellular senescence and retinoic acid on the expression of cellular
      retinoic acid binding proteins in skin fibroblasts.
AB  - Retinoic acid (RA) has significant effects on a variety of cellular processes,
      including growth and differentiation. Retinoic acid has also been implicated as a
      major morphogen during embryogenesis. In the skin, both the epidermis and the
      dermis are extremely responsive to the effects of retinoids; however, the
      molecular mechanisms through which retinoids act in this tissue remain poorly
      understood. Two classes of proteins play roles in mediating the biological
      effects of retinoic acid. The nuclear receptors for retinoic acid are of two
      types, the initially described RARs, and the RXRs. Each of these nuclear receptor
      families has multiple isoforms and can function as a ligand-inducible
      transcription enhancing factor. A second class of receptor proteins exists for
      retinoic acid that are found in the cytoplasm, the cellular retinoic acid binding
      proteins (CRABPs). These proteins play a role in the binding, transport, and
      metabolism of retinoic acid. In previous studies, we have demonstrated that
      retinoic acid induces the expression of RAR beta and RAR gamma in human dermal
      fibroblasts. Moreover, we have also shown the selective transcriptional up
      regulation of the RAR beta 2 isoform in senescent dermal fibroblasts and
      senescent human mammary epithelial cells. In order to further define molecules
      important in regulating the response of senescent dermal fibroblasts to
      retinoids, we demonstrate here that retinoic acid induces CRABP-II messenger RNA
      in human dermal fibroblasts in a dose-dependent manner. Moreover, we show that
      the induction by RA can be inhibited by actinomycin D, suggesting that the up
      regulation may be mediated by a transcriptional mechanism. We further demonstrate
      that cycloheximide also has an effect on the up-regulation, suggesting a role for
      protein synthesis in the regulation of CRABP-II gene expression. We show that
      CRABP-II is a very stable messenger RNA species, in contrast to the mRNAs for RAR
      alpha, RAR beta, and RAR gamma. Of interest, we demonstrate no significant
      difference in the expression of CRABP-II between presenescent and senescent
      fibroblasts. Taken together, these data suggest that retinoic acid plays a
      central role in the regulation of CRABP-II gene expression in the dermal
      fibroblast and that this molecule is the major mediator of the cytoplasmic
      effects of retinoids in dermal fibroblasts. However, in contrast to RAR beta 2,
      there is no apparent change in the regulation of CRABP-II in senescent dermal
      fibroblasts.

PMID- 7628541
TI  - Analysis of collagen synthesis and assembly in culture by immortalized mouse
      chondrocytes in the presence or absence of alpha 1(IX) collagen chains.
AB  - We have previously shown that SV40 large T oncogene is able to induce mouse
      chondrocyte proliferation without loss of expression of types II, IX, and XI
      collagen, as well as cartilage aggrecan and link protein. The cell line obtained
      (termed MC 615) also expressed some type I collagen in monolayer and we have
      investigated if anchorage-independent conditions could inhibit type I collagen
      synthesis and promote hypertrophy and type X collagen synthesis. The MC 615 cells
      were grown in agarose in the presence of serum, and GAG accumulation, DNA
      content, and matrix synthesis rates were monitored after incubation with
      [35S]sulfate and [3H]- or [14C]proline. SDS-PAGE analysis of pepsin-extracted
      samples showed that type I collagen was still synthesized by the MC 615 cells,
      from the beginning of the culture and at low or high density. Type II collagen
      synthesis was demonstrated by immunoblotting, but type X collagen synthesis was
      not detected, indicating that the MC 615 chondrocytes immortalized by large T
      were still blocked in their maturation pathway. The cells were also grown over
      agarose and electron microscopy (E. M.) analysis of the cell aggregates showed an
      extracellular matrix rich in proteoglycans and in type II-containing collagen
      fibrils. To gain insight into the role of type IX collagen in cartilage collagen
      assembly and/or matrix organization, we also immortalized embryonic chondrocytes
      isolated from mice lacking alpha 1 (IX) collagen and obtained a clone termed 4KO
      91. As found for the MC 615 cells, the 4KO 91 cells synthesized type II collagen
      as demonstrated by Western blotting and some type I collagen identified by the
      presence of alpha 2(I) chains after electrophoretic analysis of pepsin-digested
      collagen chains. E. M. analysis of the extracellular matrices synthesized by the
      two cell lines revealed differences in collagen structure and organization. In
      the absence of alpha 1 (IX) collagen chains, the collagen fibrils seemed to fuse
      laterally, suggesting that collagen IX acts as a "spacer" between fibrils, to
      keep them apart.

PMID- 7628543
TI  - Quantitative changes of the two major AgNOR proteins, nucleolin and protein B23,
      related to stimulation of rDNA transcription.
AB  - The relationship between the amount of the two major AgNOR proteins, nucleolin
      and protein B23, and the rate of ribosomal RNA (rRNA) synthesis was studied in
      cortisol-treated and regenerating rat hepatocytes after partial hepatectomy. In
      both experimental models the synthesis of rRNA was greatly stimulated, but only
      in regenerating hepatocytes was the increased synthesis associated with cells
      entering the mitotic cycle. Nucleolin and protein B23 were identified on SDS
      polyacrylamide gels of nuclear proteins transferred to nitrocellulose and
      detected (1) by immunoreaction with specific monoclonal antibodies revealed by
      second antibodies coupled to peroxidase followed by chemiluminescence or (2) by
      the silver-staining procedure for AgNOR proteins. Nucleolin and protein B23 were
      then quantified by computerized densitometric analysis of the immunolabeling
      signals or the silver-stained bands at 105 kDa (nucleolin) and 39 kDa (protein
      B23). The synthesis of rRNA was measured by evaluating the amount of
      radioactivity incorporated into pre-rRNA after [3H]orotic acid injection.
      Densitometric analysis of silver-stained bands and immunolabeling signals showed
      no change in nucleolin and protein B23 amounts in cortisol-stimulated
      hepatocytes, whereas a moderate increase was found in regenerating hepatocytes at
      12 h after partial hepatectomy. In both cortisol-stimulated and regenerating
      hepatocytes the synthesis of rRNA was highly increased (2.6-fold and 4.3-fold
      above the control level, respectively). To ascertain the relationship between
      quantitative changes in nucleolin and protein B23 and stimulation of rRNA
      transcriptional activity in regenerating hepatocytes, the quantitative
      distribution of these proteins was also investigated in the early times of
      regeneration using silver-stained nitrocellulose-transblotted nuclear proteins.
      The quantity of protein B23 was unchanged until 12 h after partial hepatectomy,
      whereas nucleolin appeared to be slightly increased at 9 h (1.15-fold above the
      control value) after partial hepatectomy. On the other hand, at just 6 h after
      partial hepatectomy, a significant increase of rRNA synthesis occurred in
      regenerating rat hepatocytes (1.8-fold above the control value). These data
      demonstrated that stimulation of rRNA transcriptional activity occurring in rat
      hepatocytes after cortisol treatment and in the early times after partial
      hepatectomy was not associated with quantitative changes in the amounts of
      nucleolin and protein B23.

PMID- 7628542
TI  - The effect of neomycin on PDGF-induced mitogenic response and actin organization
      in cultured human fibroblasts.
AB  - Actin organization and DNA synthesis were studied in cultured, serum-starved,
      subconfluent human fibroblasts in response to human recombinant platelet-derived
      growth factor (PDGF)-BB and neomycin, an inhibitor of phosphoinositide (PI)
      turnover. The labeling of F-actin with TRITC-phalloidin showed that PDGF (10
      ng/ml) and neomycin (3.5 mM) induced, within minutes, similar changes in the
      actin cytoskeleton and when used together potentiated each other's effects. PDGF
      stimulated a twofold increase in DNA synthesis, as shown by [3H]thymidine
      incorporation, 48 h after the beginning of incubation. Neomycin did not induce
      DNA synthesis but reduced the mitogenic response to PDGF to control levels.
      Stimulation of DNA synthesis was correlated with an intense increase in
      lamellipodia formation and ruffling, whereas inhibition of the DNA synthesis was
      correlated with the development of elongated cell shape with few ruffles and
      lamellipodia, similarly to untreated control cells. Our findings support the
      conclusion that early changes in the actin cytoskeleton and induction of DNA
      synthesis are separable biological processes that are mediated by different
      pathways. The inhibitory effect of neomycin on PDGF-induced DNA synthesis was
      dose-dependent during the first 24 h of PDGF incubation, after which the cells
      were irreversibly and maximally stimulated to synthesize DNA. Results of
      experimental treatments with neomycin at various times during the incubation with
      PDGF indicate that the critical period during which PDGF acts to stimulate DNA
      synthesis is after the 1st h but before the 12th h of incubation.

PMID- 7628544
TI  - Aphidicolin-sensitive DNA polymerase is incorporated into the chromatin during
      nuclear envelope assembly in Xenopus egg extract.
AB  - The mechanism for incorporation of aphidicolin-sensitive DNA polymerase into
      reconstituting sperm nuclei was studied in a Xenopus egg extract cell-free
      system. Aphidicolin-sensitive DNA polymerase activity was sedimented along with
      the light membrane fraction of Xenopus egg extract on a discontinuous sucrose
      gradient. Treatment of the egg extract with Triton X-100 caused DNA polymerase
      activity to migrate to a lighter density position at which free proteins were
      distributed. DNA polymerase activity was incorporated into the reconstituting
      sperm nuclei from the egg extract, but no nuclear incorporation was observed in
      nuclei incubated in egg extracts which had been treated with Triton X-100 or
      sonicated. The incorporation was also prohibited by several different treatments
      of the egg extract resulting in incomplete assembly of the nuclear membrane on
      the sperm nuclei. On the other hand, there was no inhibition of nuclear
      incorporation into the sperm nuclei reconstituting in the extracts which had been
      depleted of WGA-binding pore complex proteins or which contained a specific
      inhibitor of topoisomerase II (ICRF-193). In these two cases, the nuclear double
      layered membrane assembled normally, although in the former case the sperm nuclei
      lacked lamina and did not initiate DNA replication, and in the latter case the
      sperm nuclei did not decondense but initiated DNA replication. Thus, it is
      concluded that DNA polymerase activity is incorporated into the reconstituting
      nuclei via the membraneous/particulate fraction of the egg extract simultaneously
      with nuclear double-layered membrane assembly. The lamina assembly and the
      transport system via the nuclear envelope pore complex are suggested not to
      participate in DNA polymerase nuclear incorporation.

PMID- 7628545
TI  - Protein-protein interactions between human nuclear lamins expressed in yeast.
AB  - Protein-protein interactions between the nuclear lamins are responsible for the
      assembly of the nuclear lamina, a meshwork of intermediate filaments associated
      with the nuclear envelope inner membrane. We have used the yeast two-hybrid
      system to examine the interactions between the predominant human nuclear lamins
      expressed as GAL4 fusion proteins in Saccharomyces cerevisiae. Lamin A, prelamin
      A, lamin B1, and lamin C were able to form homodimers as well as heterodimers.
      Analysis of the different structural domains of lamin B1 demonstrated that the
      second half of coil 2 of the rod domain was necessary for the formation of the
      most stable homodimers. The results show that the yeast two-hybrid system can be
      used to study the interactions between structural proteins and their domains.

PMID- 7628546
TI  - Loss of protein kinase C delta from human HaCaT keratinocytes upon ras
      transfection is mediated by TGF alpha.
AB  - The spontaneously immortalized human skin keratinocytes HaCaT contain protein
      kinase C (PKC) alpha, -delta, -epsilon, and -zeta. All PKC isoenzymes except PKC
      zeta are down-regulated by TPA as well as by bryostatin. However, with PKC delta,
      bryostatin but not TPA was found to be much less effective at high concentrations
      than at low ones. PKC delta expression at the protein and mRNA level is
      significantly suppressed in HaCaT cells I-7 and II-4, which are transfected with
      mutated c-Ha-ras. The expression of the other isoenzymes remains essentially
      unchanged in the ras-transfected cells compared to normal ones. PKC delta is lost
      when growing HaCaT cells in a medium obtained from the cultivation of ras
      transfected cells ("ras-conditioned" medium). The factor secreted into the medium
      by the ras-transfected cells that is responsible for this effect appears to be
      TGF alpha, since the action of ras-conditioned medium on PKC delta expression can
      be overcome by the addition of an anti-TGF alpha antibody. Moreover, treatment of
      HaCaT cells with TGF alpha suppresses selectively the expression of the PKC
      isoenzyme delta.

PMID- 7628547
TI  - Senescence-dependent regulation of type 1 plasminogen activator inhibitor in
      human vascular endothelial cells.
AB  - Type 1 plasminogen activator inhibitor (PAI-1) is the primary inhibitor
      plasminogen activator and has been found to be increased in a number of clinical
      conditions generally defined as prothrombotic. Since in aging and in
      atherosclerosis the changes observed in the endothelium resemble those of in
      vitro aged endothelial cells, we have examined the expression of PAI-1 in cells
      at different population doublings. In senescent endothelial cells, PAI-1 mRNA and
      protein are constitutively high, but uninducible by exogenous interleukin 1 alpha
      as well as by the phorbol ester TPA. Interestingly the increase of PAI-1 levels
      correlates with the upregulation of interleukin 1 alpha, which characterizes
      endothelial cell senescence. Since PAI-1 expression is not increased in young
      cells made nondividing by contact inhibition, we anticipate that PAI-1 expression
      can be used as an appropriate marker of endothelial senescence. Moreover, PAI-1
      was not upregulated in senescent or in progeric human fibroblasts, which do not
      overexpress interleukin 1 alpha, thus suggesting that multiple pathways may exist
      to regulate aging of human fibroblasts and endothelial cells.

PMID- 7628548
TI  - Ultrastructural evidence of differential solubility in Triton X-100 of
      endothelial vesicles and plasma membrane.
AB  - Endothelial plasmalemmal vesicles (EV) are distinct membrane-bound structures
      characteristic for all vascular endothelia, being involved in transcytosis of
      plasma macromolecules. EV are considered to be similar to the caveolae
      (characterized by a specific peptide called caveolin) found in other cell types.
      Caveolin-rich membrane domains were recently isolated from whole lung and chicken
      gizzard as a Triton X-100 (TX)-insoluble membrane fraction. However,
      ultrastructural data on the localization of these domains within cells have not
      yet been reported. We have examined whether EV are TX-insoluble structures.
      Cultured bovine aortic endothelial cells (BAEC) briefly fixed in paraformaldehyde
      (10 min, 37 degrees C) were exposed to 0.1% TX for 5 min at 22 degrees C and
      further subjected to standard electron microscopy procedure. The results showed
      an extensive solubilization of endothelial plasmalemma as well as other
      intracellular membranes. Individual or clusters of EV were not affected by TX
      extraction, retaining their trilaminar unit membrane appearance and dimensions.
      Moreover, a crude membrane fraction prepared from unfixed BAEC was also extracted
      with 1% TX for 20 min at 4 degrees C and the insoluble material was examined by
      electron microscopy. In this fraction clusters of about 10 membranous vesicles
      were found. These data suggest that EV and plasma membrane have a different lipid
      composition; the low TX solubility is a characteristic common to caveolin-rich
      domains (caveolae) of other cells types and EV, whereas the ultrastructural
      complexity and intracellular localization of the latter are specific for
      endothelia.

PMID- 7628549
TI  - Independent mechanisms are utilized for the coordinate and transient accumulation
      of two differentiation-specific mRNAs during differentiation of Naegleria gruberi
      amoebae into flagellates.
AB  - During the differentiation of Naegleria gruberi amoebae into flagellates, four
      differentiation-specific (DS) mRNAs are transiently and coordinately accumulated.
      Three of the four DS mRNAs, Class II, III, and IV, encode alpha-tubulin, beta
      tubulin, and flagellar calmodulin, respectively. The protein product of the Class
      I mRNA has not been identified. We examined the effects of inhibition of protein
      synthesis on transcription and accumulation of beta-tubulin mRNA and Class I mRNA
      to understand the mechanism of coordinate regulation. Inhibition of protein
      synthesis at the beginning of differentiation completely blocked transcription of
      the beta-tubulin gene. Addition of cycloheximide at 30 or 40 min after initiation
      of differentiation inactivated transcription of the beta-tubulin gene in less
      than 10 min as judged by nuclear run-on experiments. However, once
      differentiation had proceeded for more than 50 min, inhibition of protein
      synthesis did not inactivate transcription of beta-tubulin mRNA was more active
      in cycloheximide-treated cells than in control cells. Cycloheximide treatment at
      the initiation of the differentiation also blocked transcription of the Class I
      gene. However, addition of the drug after 30 min had no significant effect on the
      transcription of the Class I gene. Cycloheximide treatment also increased the
      half-lives of beta-tubulin and Class I mRNA drastically. These data suggest that:
      (1) the transient accumulation of the two DS mRNAs during differentiation are
      regulated by changing both the rate of transcription and the stability of the
      mRNAs; (2) protein synthesis is required for the transcriptional and post
      transcriptional regulations; (3) the transcriptional regulation mechanisms of the
      beta-tubulin gene and that of the Class I gene are distinct; and (4) the
      transcription of the beta-tubulin gene is regulated by different mechanisms
      during differentiation.

PMID- 7628550
TI  - Pretreatment with oleic acid accelerates the entrance into the mitotic cycle of
      EGF-stimulated fibroblasts.
AB  - We have previously demonstrated that pretreatment of several cell lines with cis
      unsaturated fatty acids, like oleic acid, blocks epidermal growth factor (EGF)
      induced early ionic signals, and in particular the [Ca2+]i rise. In the present
      work we show that this blockade does not alter EGF-stimulated cellular
      proliferation evaluated by direct cell counting, but induces a powerful
      enhancement in the pulsed thymidine incorporation assay. The lack of effect of
      oleic acid on EGF-stimulated cellular proliferation was confirmed by repeated
      cell counts, cumulative thymidine incorporation, and protein synthesis, but a
      clear synergistic effect between oleic acid and EGF was again obtained by means
      of time course experiments with pulsed thymidine. Combined flow cytometry
      analysis and cell counts at earlier times in EGF-stimulated cells showed that
      oleic acids accelerates the entrance of cells into the replicative cycle leading
      to an earlier cell division. Afterward, these oleic acid-pretreated cells became
      delayed by an unknown compensatory mechanism in such a way that at 48 h post-EGF,
      the cell count in control and oleic acid-pretreated cells was equal. In
      conclusion (a) oleic acid accelerates or enhances the EGF mitogenic action and
      (b) in the long term cells compensate the initial perturbation with respect to
      untreated cells. As a side observation, the widely employed pulsed thymidine
      incorporation method as a measure of cell division could be extremely misleading
      unless experimental conditions are well controlled.

PMID- 7628551
TI  - Developmental expression and molecular cloning of REMP, a novel retinal
      epithelial membrane protein.
AB  - The retinal pigment epithelium (RPE), like other transport epithelia, has a
      polarized distribution of membrane and cytoskeletal proteins. The establishment
      of a polarized phenotype is an essential step in the differentiation of the RPE
      and the development and maintenance of visual function. Using a monoclonal
      antibody (MAb 3C4) we have identified a novel membrane protein that is uniquely
      expressed in chick RPE. We have referred to this protein as REMP for retinal
      epithelial membrane protein. In these studies we characterized the expression and
      distribution of this protein during embryonic development and determined its
      primary structure by cDNA cloning. The developmental expression of REMP was
      examined by immunocytochemical localization. REMP was first detected in the chick
      RPE at Embryonic Day 5 (E5) in both apical and basolateral membranes. By E14 the
      distribution of REMP was restricted to the basolateral surface of the RPE cells.
      Biochemical fractionation and surface labeling of RPE cells suggested that REMP
      was an integral protein. The gene encoding REMP was isolated from an E15 chick
      RPE cDNA library, cloned into lambda gt11, and screened with MAb 3C4. The cDNA
      was sequenced and found to contain one 1350-bp open reading frame encoding for a
      450-amino-acid protein. The deduced amino-acid sequence of REMP shares 32.9%
      identity with MCT1, a monocarboxylate transporter (Garcia, Goldstein, Pathak,
      Anderson, and Brown, Cell, 76, 865-873, 1994). By Northern blot analysis, REMP
      mRNA was detected only in RPE cells. There was an increase in the expression REMP
      transcript during development but when RPE cells were grown in primary culture
      the expression of REMP was turned off. The unique expression of REMP in the RPE
      in vivo would suggest a role for this protein in development and maintenance of
      normal retinal function.

PMID- 7628552
TI  - Effect of antibodies to membrane skeletal proteins on the shape of erythrocytes
      and their ability to respond to shape-modulating agents. Important role of 4.1
      protein in the determination/maintenance of the discoid shape of erythrocytes.
AB  - Monospecific anti-spectrin, anti-4.1 protein, anti-ankyrin, and anti-band 3
      cytoplasmic domain antibodies were individually internalized in human
      erythrocytes by hypotonic lysis in the presence of 2 mM Mg-ATP. The
      concentrations of the polyclonal antibodies, or their Fab fragments, varied from
      0.5 to 4.0 mg/ml. After resealing and glutaraldehyde fixation, the shape of the
      erythrocytes was examined by phase-contrast or scanning electron microscopy. The
      antibody-internalized cells were also treated, prior to fixation, with
      dinitrophenol, chlorpromazine (membrane-penetrable crenation- and cup-forming
      agents, respectively), or serum albumin (membrane nonpenetrating cup-forming
      agent). Anti-spectrin antibodies produced a cup shape in the cells at low
      concentrations (0.5 mg/ml), with a few cells showing multiple cavities. The
      proportion of the latter increased with increasing concentration of the antibody.
      The Fab fragments of the antibody were without any effect on the shape. At lower
      concentrations of anti-4.1 antibodies (0.5 and 1 mg/ml), crenations were observed
      in antibody-internalized cells. At higher antibody concentrations, the cells
      underwent sphering. These looked dense under the phase-contrast microscope and
      often were found to project vesicles from their surface via long stalks. These
      were generally absent on cells when viewed under the electron microscope,
      probably due to their breakage during processing. The Fab fragments of the anti
      4.1, at equimolar concentrations, were as effective as the intact antibody in
      altering the cell shape. Anti-ankyrin antibodies or the Fab fragments produced no
      effect on the shape of the cell. The intact anti-band 3 cytoplasmic domain
      antibodies, but not their Fab fragments, produced cups at low concentrations and
      multiple cavities at higher concentrations and multiple cavities at higher
      concentrations. The anti-spectrin- and anti-band 3 cytoplasmic domain
      internalized cells resisted the shape-modulating actions of dinitrophenol,
      chlorpromazine, and serum albumin. The anti-4.1 antibody-internalized cells also
      did not respond to dinitrophenol and serum albumin; however, they were converted
      to contracted cups in the presence of high concentration of chlorpromazine. The
      cells in which anti-ankyrin antibodies were internalized responded to the actions
      of the shape-changing agents similarly to normal cells. The results show that the
      4.1 protein plays an important role in the determination or maintenance of the
      normal shape of the erythrocyte and that the cells possessing antibody-modified
      membrane skeleton do not respond to amphiphilic ions in the manner that normal
      cells do.

PMID- 7628553
TI  - Colon absorptive epithelial cells lose proliferative response to TGF alpha as
      they differentiate.
AB  - As colon epithelial cells migrate up the cylindrical colonic crypt, they
      terminally differentiate and lose their ability to divide. Elevated levels of the
      epithelial cell mitogen TGF alpha have been found at the top of the crypt by
      other investigators, causing us to speculate that colon epithelial cells lose
      mitogenic response to TGF alpha as they differentiate. We tested this hypothesis
      by using the HT29 colon carcinoma sublines U4 and U4H as models of one colonocyte
      lineage, fluid-transporting enterocytes. TGF alpha was mitogenic for the U4
      cells, but inhibited the growth of the more differentiated U4H cells. However,
      p44 MAP kinase was activated by TGF alpha in both U4 and U4H cells, as well as in
      two control undifferentiated HT29 sublines which showed no change in
      proliferation in response to TGF alpha. In addition, TGF alpha activated the EGF
      receptor in each line by increasing its tyrosine phosphorylation. No relationship
      was found in these four lines between response to TGF alpha and level of
      expression of either the EGF receptor or two EGF receptor ligands, TGF alpha and
      amphiregulin. Activated EGF receptors initiate both growth-inhibitory and
      mitogenic signals in these cells since blocking some of the EGF receptors on TGF
      alpha-growth-inhibited U4H cells and TGF alpha-unresponsive U9 cells overrode the
      inhibitory signals and made both U9 and U4H cells sensitive to mitogenesis by
      added TGF alpha. These data imply that upon reaching stages of greater
      maturation, colon enterocytes lose proliferative response to TGF alpha because of
      changes in signaling by their EGF receptors.

PMID- 7628554
TI  - Elevated expression of mitochondrial cytochrome b and NADH dehydrogenase subunit
      4/4L genes in senescent human cells.
AB  - In order to isolate cDNAs expressed differentially in senescent cells, we
      constructed a cDNA library from poly(A)+ RNA of senescent human fibroblast cells
      and screened cDNAs by the differential screening method. We isolated five cDNA
      clones expressed preferentially in the senescent cells. These five cDNA clones
      fell into two groups by cross-hybridization. Sequence analysis revealed that
      these cDNA clones were homologous to the human mitochondrial genes for cytochrome
      b (cytb) and NADH dehydrogenase subunit 4/4L (ND4/4L). Northern blot analysis
      demonstrated that the expression of these two mitochondrial genes were elevated
      in senescent cells compared to young cells. However, the expression of the
      mitochondrial cytochrome oxidase I gene was similar between young and senescent
      cells, implying that the preferential expression of the mitochondrial genes in
      the senescent cells was selective for cytb and ND4/4L genes. The results suggest
      that expressions of mitochondrial cytb and ND4/4L genes are regulated by a
      senescence-dependent mechanism.

PMID- 7628556
TI  - 24th Annual meeting of the International Society for Experimental Hematology.
      Dusseldorf, Germany, August 27-31, 1995. Abstracts.

PMID- 7628555
TI  - The cytotoxicity of human immunodeficiency virus type 1 Rev: implications for its
      interaction with the nucleolar protein B23.
AB  - Human immunodeficiency virus type 1 (HIV-1) encodes several regulatory proteins,
      including two essential trans-activators for viral replication, Rev and Tat. Both
      Rev and Tat have a nucleolar targeting signal and are actually located
      predominantly in the nucleoli. Within the nucleoli, Rev is localized to the
      combined regions of the dense fibrillar (DFC) and the granular (GC) components.
      Tat does not colocalize precisely with any nucleolar component tested, but partly
      overlaps regions of the DFC and the GC. Regions of both Rev and Tat are
      overlapped by the distribution of the major nucleolar protein B23. Overexpression
      of Rev causes nucleolar ballooning and general structural deformity with aberrant
      accumulation of rRNAs, whereas Tat does not have that effect. B23 is markedly
      accumulated in those nucleoli deformed by Rev. Components of the nucleolar DFC,
      GC, and fibrillar center domains are not accumulated but dispersed in few small
      spots or larger patches within the enlarged nucleoli. Cytophotometric DNA
      determinations revealed that transient expression of Rev results in accumulation
      of G2, prophase, and mitotic cells which have failed cytokinesis, suggesting that
      Rev is capable of preventing or slowing the progression through mitosis. Tat, in
      contrast, does not affect the cell cycle. We speculate, based on these results,
      that Rev represses cell growth by inhibiting the transport of ribosomal proteins
      and preribosomal particles across the nuclear envelope and affecting the cell
      cycle, both of which may be related to proposed functions of B23.

PMID- 7628557
TI  - Plasmodium falciparum: detection of P-glycoprotein in chloroquine-susceptible and
      chloroquine-resistant clones and isolates.
AB  - Recent studies have suggested the potential involvement of multidrug resistance
      (mdr) genes in resistance to quinoline-containing compounds in Plasmodium
      falciparum parasites. Three different antibodies were used to detect the malarial
      mdr 1 protein product by indirect immunofluorescence and/or immunoblot in fresh
      clinical isolates and clones of P. falciparum from different geographic origins.
      A 160-kDa protein was detected in all five parasite clones by immunoblot and
      around the food vacuole by IFA, regardless of the level of sensitivity to
      chloroquine and the modulation by desipramine of chloroquine accumulation. Our
      results suggest that chloroquine resistance is not correlated with the presence
      of the Pfmdr1 product.

PMID- 7628558
TI  - Fasciola hepatica: localisation of glutathione S-transferase isoenzymes in adult
      and juvenile liver fluke.
AB  - Four cDNA clones (GST-1, -7, -47, and -51) encoding isoenzymes of the
      detoxification enzyme glutathione S-transferase (GST) have previously been
      identified and characterised from Fasciola hepatica. In the present study,
      antisera were generated to synthetic peptides of regions unique to each of the
      four GST proteins predicted by the cDNAs. The antisera were characterised, and
      two were found to distinguish GST-1 from GST-7, GST-47, and GST-51 as a group.
      These two antisera were used to localise different GSTs in adult and newly
      excysted juvenile F. hepatica. The antiserum to GST-1 was specific and localised
      GST-1 to the parenchyma of adult fluke but not to the lamellae of the intestinal
      caeca. The antiserum to a GST-51 peptide, which cross-reacted with GST-7 and GST
      47 but not GST-1, localised the other GSTs not only to the parenchyma but also to
      the intestinal lamellae of adult fluke. This appears to be the first evidence of
      tissue-specific expression of GST isoenzymes in trematodes. In contrast to adult
      fluke, immunolocalisation of the GSTs in juvenile F. hepatica revealed the
      binding of both the GST-1 and GST-51 antisera to the parenchymal cytoplasm, to
      cytoplasmic extensions of the parenchyma cells in the subtegumental area, as well
      as the excretory ducts. No labeling was observed in the intestinal epithelium of
      the juvenile fluke. These results demonstrate that adult F. hepatica, in contrast
      to juvenile flukes, contain a GST, which is not GST-1, associated with the
      lamellae of the gut and suggest that GSTs in adult fluke may play a role in the
      absorptive function of the adult gut.

PMID- 7628559
TI  - Plasmodium berghei: implication of intracellular glutathione and its related
      enzyme in chloroquine resistance in vivo.
AB  - Glutathione (GSH) plays a critical role in the detoxication and the protection of
      cells against oxidative stress. In the present study we examined the relationship
      between the intracellular GSH levels as well as glutathione S-transferase (GST),
      glutathione reductase (GR), and glutathione peroxidase (GPx) activities and how
      they relate to Plasmodium berghei resistance to chloroquine. Resistant strains
      (CQR30 and CQR60) were selected in vivo from a sensitive strain (NK65). Marked
      increases in GSH levels and GST activity within resistant parasites were
      observed, compared to sensitive parasites. On the other hand, GR and GPx
      activities were similar in sensitive and resistant parasites. Treatment with
      chloroquine did not influence the intracellular level of GSH, but it was found to
      significantly decrease GR activity. Intracellular depletion of GSH, by a nontoxic
      concentration of buthionine sulfoximine (BSO), significantly sensitized the
      resistant parasites to chloroquine. These results suggest that the P. berghei
      resistance results from altered GSH and GST levels and activity, respectively,
      which enable the detoxification of chloroquine in resistant parasites.

PMID- 7628560
TI  - Biochemical, immunological, and biological characterization of Trypanosoma cruzi
      populations of the Andean north of Chile.
AB  - Twenty-one Trypanosoma cruzi stocks isolated from Triatoma infestans and humans
      of the Chilean Andean highlands were studied at the genotypic level by schizodeme
      and molecular karyotype analyses, which allowed a clear distinction of the
      parasites from those hosts. A phenotypical characterization was performed by
      proteolytic activity after electrophoretic fractionation without discrimination
      among the stocks. Metacyclic trypomastigotes obtained in vitro proved to be
      infective to Swiss mice and the study of immune response and biological behavior
      was assessed. Of a total of 21 T. cruzi stocks, only 11 proved to be infective in
      mice due to difficulties in obtaining metacyclic trypomastigotes with the
      parasite populations isolated from humans. Western blot analysis revealed a
      complex immune response even in the first days postinfection with each T. cruzi
      strain studied. Antigenic recognition by each immune serum is characteristic,
      although several major and common antigens were detected. Lytic antibodies were
      studied by the in vitro complement-mediated lytic assay using purified metacyclic
      trypomastigotes as target cells. All the T. cruzi isolates tested induced lytic
      antibodies in this experimental model. Parasitemias were moderate and
      characteristic for each T. cruzi strain. Results are compared with metacyclic
      forms of the infective and pathogenic Tulahuen strain.

PMID- 7628561
TI  - Strongyloides stercoralis: complete life cycle in SCID mice.

PMID- 7628562
TI  - Aldehyde fixation dramatically alters the immunolocalization pattern of
      paramyosin in platyhelminth parasites.

PMID- 7628563
TI  - An isoenzyme survey of Trypanosoma cruzi genetic variability in sylvatic cycles
      from French Guiana.
AB  - Twenty-seven trypanosomatidae stocks isolated from various hosts in French Guiana
      have been surveyed by Multilocus Enzyme Electrophoresis on cellulose acetate
      plates. The variability observed at 22 different enzyme systems was considerable,
      since 21 different enzyme profiles (zymodemes) could be distinguished. Clustering
      analysis and comparison with four laboratory reference stocks showed clearly that
      three stocks were distantly related from the rest and most probably cannot be
      included in the species Trypanosoma cruzi. All the other stocks were more related
      to the formerly described zymodeme I than to the formerly described zymodemes II
      and III. Genotype variability in this T. cruzi sylvatic population was notably
      higher than in domestic populations of the same parasite. This could suggest more
      frequent genetic exchange occurring in sylvatic cycles. Nevertheless, a
      population genetic analysis of the data showed a considerable linkage
      disequilibrium, which rather favors the hypothesis that T. cruzi has a basically
      clonal population structure in this ecosystem too.

PMID- 7628564
TI  - Eimeria tenella: sporozoites rarely enter leukocytes in the cecal epithelium of
      the chicken (Gallus domesticus).
AB  - In this study, the intraepithelial leukocytes supposedly involved in the
      transportation of Eimeria tenella sporozoites through the cecal lamina propria
      were phenotypically characterized. The ceca of naive and immune chickens were
      examined at various times after inoculation by light microscopy and
      immunocytochemical techniques. The distribution of sporozoites within the villus
      differed markedly between both groups. From 16 hr postinoculation, significantly
      fewer sporozoites had reached the crypts in immune chickens, and schizont
      formation was inhibited. In the villus epithelium of both naive and immune
      chickens, few sporozoites were found within a leukocyte. Using anti-sporozoite
      and anti-CD45 monoclonals, we showed that even when intraepithelial leukocytes
      are abundantly present, only a few sporozoites were inside them. In the lamina
      propria of immune chickens significantly more sporozoites were found within
      leukocytes than in the lamina propria of naive chickens. The phenotype of the few
      leukocytes that harbored sporozoites was similar in naive and immune chickens. A
      few sporozoites were detected in B cells, 10% in macrophages, and 50% in T cells,
      especially CD8+ cells. These results show that E. tenella sporozoites rarely
      enter intraepithelial leukocytes and therefore their putative role in
      transporting sporozoites through the lamina propria is doubtful.

PMID- 7628565
TI  - Effects of bis(benzyl)polyamine analogs on Leishmania donovani promastigotes.
AB  - A number of bis(benzyl)polyamine analogs were found to be potent inhibitors of
      Leishmania donovani growth in vitro (IC50 = 4.3-25 microM). Structural variations
      appear to have important effects on the biological functions of these analogs.
      Subinhibitory concentration of all of the analogs with the exception of MDL 27994
      could rescue the cells from DL-alpha-difluoromethylornithine toxicity. The
      analogs inhibited macromolecular synthesis as evaluated by [3H]thymidine,
      [14C]uracil, and [35S]methionine incorporation. They inhibited the activity of
      the two enzymes, ornithine decarboxylase (ODC) and S-adenosylmethionine
      decarboxylase (AdoMetDC), involved in the biosynthesis of polyamines. These
      analogs depleted intracellular levels of natural polyamines. We conclude,
      therefore, that the major mechanism by which these analogs act may be by
      disruption of macromolecular biosynthesis and cell death. Repression of
      polyamines by these analogs may be yet another factor involved in slowing the
      growth of the parasite.

PMID- 7628567
TI  - Plasmodium berghei: selection of mefloquine-resistant parasites through drug
      pressure in mosquitoes.
AB  - Mefloquine is an antimalarial drug with schizonticidal activity on blood-stage
      parasites. Studies of the role of mefloquine on the development of Plasmodium
      berghei ANKA in anopheles stephensi have been carried out that showed a dose
      dependent effect on the sporogonic cycle of these parasites, with changes in the
      numbers of oocysts and the extent of sporozoite invasion of salivary glands. In
      this study, we show that mefloquine-resistant P. berghei ANKA blood stage
      parasites could be selected through drug pressure during continuous cyclical
      transmission of Anopheles gambiae s.l.

PMID- 7628566
TI  - Plasmodium falciparum: variations within the C-terminal region of merozoite
      surface antigen-1.
AB  - Sequence variations at the 3'-end of the Plasmodium falciparum merozoite surface
      antigen-1 gene show that the C-terminus of the protein may not be as conserved as
      has been assumed in the past. We have therefore examined the sequences of the 3'
      terminal 2 kb, i.e., blocks 12-17 of four isolates, RO-33, RO-71, 3D7A, and FCH5.
      We discuss different mechanisms of genetic exchange that could account for the
      observed variations. Furthermore the deduced amino acid sequences allow us to
      identify allelic epitopes of three monoclonal antibodies. Finally, our data
      complete the sequence of two additional independent alleles of this gene (RO-33
      and RO-71).

PMID- 7628568
TI  - Dirofilaria immitis: immunohistochemical localization of acid proteinase in the
      adult worm.
AB  - The distribution of Dirofilaria immitis acid proteinase in adult worm tissue was
      examined biochemically and immunohistochemically. About 45% of the total
      proteinase activity of 700g supernatant, which was obtained from the 0.25 M
      sucrose homogenate of live adult worms, was found in the 100,000g supernatant by
      subcellular centrifugation analysis. The distribution pattern of the proteinase
      activity observed by Percoll density gradient centrifugation coincided with that
      of glucose-6-phosphatase, a marker cytosolic enzyme, suggesting that the acid
      proteinase was present in vivo in a membrane-free form, possibly in the cytosol
      or secretory fluid. Immunostaining for the proteinase in the parasite tissue
      using the IgG1 (kappa-type) monoclonal antibody, H-1, revealed immunoreactive
      enzyme primarily inside the cell as small grains, but not on the cell surface,
      and immunoreactivity was distributed widely in worm tissues such as lateral
      cords, dorsal and ventral median cords, the anterior end of the parasite, and
      intestinal epithelial cells in granular form. In the male reproductive system,
      the testicular wall and germ cells were labeled with the antibody, and in the
      female, uterine walls, fertilized eggs, and developing eggs as well as
      microfilaria were labeled. In conclusion, D. immitis acid proteinase is widely
      distributed in the parasite tissue, possibly functioning not only in nutrition
      metabolism but also in production of sperm and microfilariae, etc.

PMID- 7628569
TI  - Brugia pahangi: effects of melanization on the uptake of nutrients by
      microfilariae in vitro.
AB  - The effects of melanization on nutrient uptake by the microfilariae of Brugia
      pahangi were investigated by using in vitro melanization and autoradiographic
      techniques. It was found that the melanotic capsules which formed around the
      microfilariae in vitro completely inhibited the uptake of the following
      radiolabeled nutrients into microfilarial tissues: D-[6-3H]glucose, L-[4,5
      3H]leucine, [2-3H]glycine, [1-14C]linoleic acid, [5,6,8,9,11,12,14,15
      3H]arachidonic acid, [2,8-3H]adenine, [8-14C]guanine HCl, and [5,6-3H]uracil.
      These results provide strong evidence that melanization may kill the
      microfilariae by starvation.

PMID- 7628570
TI  - Plasmodium falciparum: D260, an intraerythrocytic parasite protein, is a member
      of the glutamic acid dipeptide-repeat family of proteins.
AB  - Members of a serologically cross-reacting family of proteins including Ag332 and
      Pf11.1, megadalton proteins of schizont-infected red blood cells, and
      gametocytes, respectively, and Pf155-RESA, a 155-kDa protein of ring-infected red
      blood cells, have been reported to share amino acid repeat sequences. These
      repeats are rich in glutamic acid dipeptides postulated to be involved in
      generating serologic cross-reactivity. We report the identification and
      characterization of another member of this cross-reacting family, a 260-kDa
      glutamic acid-rich intraerythrocytic protein. Human antibodies affinity purified
      on the 260-kDa region of Western boots of trophozoite proteins of Plasmodium
      falciparum were used to screen a trophozoite-stage lambda gt11 cDNA library. A
      1.8-kb clone was identified and human antibodies were affinity purified on the
      expressing clone. Using this affinity-purified antibody and the 1.8-kb clone, the
      corresponding protein, its gene, and its chromosomal location were investigated.
      The 260-kDa corresponding protein serologically cross-reacts with Pf155-RESA, but
      is the product of a different gene. The 260-kDa protein is Triton X-100 soluble
      and is variable in molecular weight in different isolates. Immunoprecipitation of
      [35S]methionine-labeled infected red blood cells indicates that the protein is
      synthesized throughout the intraerythrocytic cycle but is most prominent in
      schizonts. The protein, as has been shown previously, is not immunoprecipitated
      from 125I surface-labeled infected red blood cells and is thus not PfEMP1, the
      antigen associated with cytoadherence. Indirect fluorescent antibody studies
      using fixed infected red blood cells suggest that the protein is localized to the
      periphery of the intraerythrocytic parasite.

PMID- 7628571
TI  - Onchocerca volvulus: a comparative study of in vitro neutrophil killing of
      microfilariae and humoral responses in infected and endemic normals.
AB  - In vitro neutrophil-mediated microfilarial killing, humoral responses to crude
      adult worm antigens (OVAg) and to four recombinant Onchocerca antigens (GST-OV7,
      GST-OV103, GST-OV3.6, and MBP-OV16), as well as Western blot analysis to stage
      specific Onchocerca proteins were studied in individuals from Bassa County,
      Liberia, infected with onchocerciasis and in endemic normals, defined as
      individuals without microfilaridermia. Both groups exhibited high levels of
      specific serum-dependent killing of microfilariae but could not be differentiated
      on the basis of these results. However, infected individuals had a significantly
      higher frequency of antibody response to OVAg (P = 0.0001) except GST-OV103.
      Based on the pattern of response to the different antigens, 17 categories of
      specific recognition were observed. Nine of these categories were common to both
      the infected individuals and the endemic normals, 2 were unique to the infected
      individuals, and 6 were unique to the endemic normals. Among the endemic normals,
      we identified a subcategory of individuals who had nondetectable levels of total
      IgG to OVAg by ELISA and had significantly lower IgG4 responses to OVAg. These
      same individuals demonstrated evidence of past infection, based on serum
      antibodies detectable by Western blot analysis to male and female adult worms and
      skin microfilariae, and had a positive response to two or less of the recombinant
      antigens. We believe that this subcategory may represent individuals with a
      unique status of immunity.

PMID- 7628572
TI  - Plasmodium falciparum: malaria morbidity is associated with specific merozoite
      surface antigen 2 genotypes.
AB  - Plasmodium falciparum merozoite surface antigen 2 (MSA2) is considered a vaccine
      candidate in a subunit vaccine against blood stage malaria. In order to test if a
      specific genotype of the highly polymorphic MSA2 is associated with disease, we
      conducted a case-control study in a malaria endemic area of Papua New Guinea
      involving 227 individuals, mostly children under the age of 10 years. All cases
      and controls were genotyped by polymerase chain reaction for their respective
      MSA2 genotypes. We report that at the time of the study parasites carrying the
      FC27-like genotype were twice as likely to be found in symptomatic malaria cases
      than in asymptomatic controls. Mixed genotype infections were significantly less
      frequent in symptomatic malaria infections. One individual allele (WOS10) of the
      FC27 family was found only in cases. This may be a form of P. falciparum
      infrequently encountered and may cause morbidity due to lack of immunity to it.
      This study provides evidence that MSA2 is involved in the morbidity of malaria
      and supports the inclusion of MSA2 in a subunit vaccine.

PMID- 7628574
TI  - The centenary of W. C. Roentgen's discovery: a look at developments in science,
      clinical radiologic practice and environmental problems.

PMID- 7628573
TI  - Antimalarial effects of C18 fatty acids on Plasmodium falciparum in culture and
      on Plasmodium vinckei petteri and Plasmodium yoelii nigeriensis in vivo.
AB  - Following the demonstration of the antimalarial effect of the long chain
      saturated alcohol n-hentriacontanol ((CH2)29CH2OH), isolated from the Bolivian
      endemic solanaceous plant Cuatresia sp., we have tested the effect of the C18
      fatty acids oleic, elaidic, linoleic, and linoleic on malaria parasites. These
      fatty acids inhibited the parasitemic development in mice infected with
      Plasmodium vinckei petteri or with Plasmodium yoelii nigeriensis in a 4-day
      suppressive test. To gain a deeper discernment of the antimalarial mode of
      action, the effects of these compounds were evaluated on Plasmodium falciparum
      growth in culture. Whereas n-hentriacontanol did not show any inhibition of this
      parasite, on the contrary, the C18 acids displayed a considerably inhibitory
      activity at < or = 200 micrograms/ml both in intact infected cells and in free
      parasites. In order to understand the mechanism of their antimalarial action,
      several tests were performed. No hemolysis of infected cells could be observed up
      to 500 microgram/ml. No effect on the lipid peroxidation, ATP levels, transport
      through the parasite-induced permeability pathways, or on the phagocytosis of the
      infected cells could be observed. The cytotoxic effect of the fatty acids was
      very rapid: full inhibition of nucleic acids and protein syntheses was observed
      in less than 30 min. This inhibition was not relieved by the addition of
      deferrioxamine or FeCl3, indicating that fatty acids (FA) do not act by
      facilitating the transport of iron. Inhibition was relieved in neither the
      presence of orotic acid or its methyl ester, indicating that FA do not act at the
      mitochondrial level of pyrimidine synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7628575
TI  - The consequences of the discovery by W. C. Rontgen for present-day medical
      physics and radiation protection.
AB  - When the German physicist W. C. Rontgen discovered X-rays, which were named after
      him, he introduced a new development in medicine and biology: together with the
      discoveries of A. H. Becquerel and M. Curie, radiology with its diagnostic and
      therapeutic methods was made possible. The medical physicist has an important
      task to fulfill in modern radiotherapy, nuclear medicine and radiodiagnostics.
      The longtime interdisciplinary collaboration has won the international
      recognition of medical physics as a scientific discipline, a health care
      profession and a university subject. Several incidents, including contemporary
      ones, show that the efforts made towards radiation protection must remain an
      important domain of the specialist.

PMID- 7628576
TI  - 100 years of radiobiology: implications for biomedicine and future perspectives.
AB  - The development of radiobiology from the very early detection of the biological
      action of X-rays to the knowledge of today is described in sections on radiation
      chemistry and biochemistry, mutation and cancer induction, and embryonic damage,
      as well as the dependence of radiation response on radiation quality and temporal
      dose distribution (repair) and the interaction with other factors. For medicine
      radiobiology serves as a basis for radiotherapy and radiological protection. The
      effect of very low doses, and their possible biopositive effect (hormesis and
      adaptive response), is also discussed, as are the health hazard of radon, health
      risks after the Chernobyl accident, and space radiobiology. The radiobiology of
      the future will be concerned with biomolecular and genetic implications, problems
      of damage and repair, and connected problems like hormesis.

PMID- 7628577
TI  - One century of diagnostic imaging in medicine.
AB  - The historical outline shows the development of radiologic diagnostics from the
      early Roentgen days up to this centenary. The roots of radiologic diagnostics go
      back to the European Renaissance. It is a history of medical pattern recognition
      and functional analysis by several methods including X-rays, ultrasound waves or
      strong magnetic fields. The difference between conventional radiographs and a
      picture reconstructed after digitalization, with several possibilities of
      postprocessing, is explained. Research and further technical revolutions, like
      the development of semiconductor elements and computers or tailored contrast
      media, sophisticated pictorial representations and perceptions, are among the
      cornerstones of imaging diagnostics. During this century many diseases have
      changed their manifestation and spread. This is illustrated by tuberculosis and
      cancer and highlights the growing importance of imaging diagnostics and
      interventional radiology. The thorny path to independence of radiology is also a
      history of the medical establishment's resistance.

PMID- 7628578
TI  - Historical essentials influencing the development of radiooncology in the past
      100 years.
AB  - An overview of the development in the recent 100 years is given. The work of the
      most important pioneers is described. Both technical preconditions and
      radiobiological fundamentals influencing advances in radiotherapy are lined out.
      It is shown that many modern techniques and therapeutical strategies have their
      origin in the beginning of radiotherapy and that this is the case for many
      unsolved problems as well.

PMID- 7628579
TI  - The impact of W. K. Rontgen's discovery on the use of internalizable sources of
      ionizing energy in diagnostic and therapeutic nuclear medicine.
AB  - The early history of cathode rays, X-rays and a third kind of natural radiation
      from several minerals and atomic fission is described. In this way the
      fundamental concept of radioactivity, laws of decay and atomic models were
      developed. With artificial radioactive isotopes, new tailored
      radiopharmaceuticals could be introduced into metabolic research, medical
      diagnostics and therapy. Von Hevesy's concept of the dynamic state of body
      constituents led to examination of the locations and movements of labelled atoms
      and molecules as a function of time. That was the birth of nuclear medicine. The
      principles and value at the molecular level of several specific tracer studies in
      research and diagnostic or therapeutic use are explained. Typically, diagnostic
      tests with tracer agents are non-invasive and have low radiation exposure.
      Competing with other diagnostic and therapeutic modalities, nuclear medicine is a
      speciality in its own right. But there are moves to classify it as a
      subspecialization of other organ-oriented clinical disciplines. That is a
      misunderstanding of the radiologist's role and does not answer the question: What
      is the best way of working for the patient? New horizons in diagnostic
      modalities, biochemistry, immunology, imaging and the use of immunogenic
      therapeutic agents demand a continuous cooperation within interdisciplinary
      teams. That is as necessary with radiologic departments, participating in changed
      organizational structures, as with other clinical departments.

PMID- 7628580
TI  - Leishmania donovani in hamsters: stimulation of non-specific resistance by novel
      lipopeptides and their effect in antileishmanial therapy.
AB  - Several novel type of lipopeptides were synthesized and evaluated for their
      ability to stimulate non-specific resistance against Leishmania donovani
      infection. Peritoneal macrophages isolated from young male hamsters treated with
      muramyl dipeptide (MDP) and various synthetic lipopeptides (6 mg/kg i.p.) 7 days
      earlier, were cultured in vitro and challenged 24 h later with L. donovani
      promastigotes. One lipopeptide, Central Drug Research Institute (CDRI) compound
      86/450, exhibited significantly higher immunostimulatory activity than MDP. Its
      prophylactic activity was further confirmed in hamsters by giving 2 split doses
      of 3 mg/kg of the compound spaced at 2 weeks, i.e. on day -7 and +7 of challenge
      with L. donovani amastigotes. The prophylactic effect lasted for 7 days following
      the last treatment with compound 86/450. The antileishmanial action of sodium
      stibogluconate (SAG) was also found to be enhanced by 16% in hamsters primed with
      compound 86/450.

PMID- 7628581
TI  - In vitro modulation of rat adipocyte ghost membrane fluidity by cholesterol
      oxysterols.
AB  - The effects of cholesterol and cholesterol-derived oxysterols (cholestanone,
      cholestenone, coprostanone and epicoprostanol) on adipocyte ghost membrane
      fluidity were studied using a fluorescence depolarization method. The
      fluorescence anisotropy of the treated membranes was determined using 1,6
      diphenyl-1,3,5-hexatriene (DPH) and 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5
      hexatriene (TMA-DPH). Cholestanone and cholesterol decreased membrane fluidity at
      both the concentrations tested (10 & 50 microM) while the rest of the sterols did
      not exert any significant effect on membrane fluidity. In the presence of
      epinephrine, cholestanone partitioned more towards the lipid core but cholesterol
      partitioning was not affected. The fusion activation energies (delta E) obtained
      for membranes preincubated with cholestanone (8.6 kcal/mol) and cholesterol (8.2
      kcal/mol) were not significantly different from that of untreated membranes (8.3
      kcal/mol). Membranes preincubated with cholestanone and cholesterol did not
      exhibit any change in lipid phase throughout the temperature range (10-45 degrees
      C) tested. The sterols were found to inhibit fisetin-induced phospholipid
      methylation in isolated rat adipocytes in the rank order of cholesterol >
      epicoprostanol > cholestanone = cholestenone = coprostanone, while basal
      methylation was unaffected. When adipocytes were preincubated with the sterols
      before the addition of fisetin, cholestanone and cholestenone showed 74% and 66%
      inhibition of maximal methylation respectively. These results indicated that
      cholesterol oxysterols interact differently with rat adipocyte membranes, with
      cholestanone interacting more with phospholipids located at the inner lipid
      bilayer (e.g. phosphatidylethanolamine) while cholesterol interacts more with
      phosphatidylcholine located at the outer lipid bilayer. This differential
      interaction may cause selective changes in membrane fluidity at different depths
      of the bilayer and thus may modulate the activities of membrane-bound proteins
      such as enzymes and receptors.

PMID- 7628582
TI  - Stereoselectivity in mammalian chemical communication: male mouse pheromones.
AB  - Two male mouse pheromones, 3,4-dehydro-exo-brevicomin (DHB) and 2-sec
      butyldihydrothiazole (SBT), are chiral molecules which were previously tested in
      their respective bioassays as racemic mixtures. The focus of this study has been
      to determine the absolute configuration of their natural forms and its relation
      to stereospecific biological action. DHB was established as the R,R-enantiomer
      possessing biological activity. Due to an extremely easy racemization of SBT
      under very mild conditions, enantioselectivity of its transmission and its action
      at the receptor site appear to be of secondary importance.

PMID- 7628583
TI  - Genetic basis of some morphological differences between temperate and equatorial
      populations of Drosophila melanogaster.
AB  - The genetic basis of three morphological traits (ovariole number, sternopleural
      bristle number and wing length) of Drosophila melanogaster has been investigated
      in natural populations that show great differences in these traits, i.e. Bordeaux
      (France) and Loua (Congo). F1 and F2 crosses, and chromosome substitutions
      between these two populations, were analysed. Maternal and/or X chromosome
      effects were found for sternopleural bristle number and wing length. For all
      traits, significant effects from each of the three chromosomes were found, but in
      general only one or two chromosomes had a major effect. Moreover, in all cases
      significant interactions between chromosomes were observed, suggesting the
      existence of epistatic effects. Our results are discussed and compared to those
      obtained from the analysis of selected laboratory strains.

PMID- 7628584
TI  - Hereditary anaemias and iron deficiency in a tribal population (the Baiga) of
      central India.
AB  - We have studied the prevalence and molecular nature of hereditary anaemias
      (abnormal haemoglobins, beta-thalassaemia, alpha-thalassaemia, and Glucose 6
      phosphate dehydrogenase (G6PD) deficiency) in a primitive central Indian tribe,
      the Baiga. 43% of the population appear to be iron-deficient. Hereditary anaemia
      gene frequencies are, sickle cell 0.0824, G6PD deficiency (in males) 0.0457, beta
      thalassaemia 0.0057, and deletional alpha-plus thalassaemia 0.65. Both -alpha 3.7
      and -alpha 4.2 deletions were observed and non-deletional alpha-thalassaemia was
      suspected. The overall gene frequency of Xmn I+polymorphism (C-->T - 158 cap
      site; upstream of G gamma region) is 0.35. This polymorphism is preferentially
      linked to beta s genes. It appears that sickle cell disease covers a wide range
      of severity in the Baiga tribe based on higher mortality in the offspring of AS x
      AS parents (2.5/couple) compared to AA x AS (0.75/couple) and AA x AA
      (0.76/couple) parents. This is compatible with the high frequency of genetic
      modifying factors, i.e., the Xmn I polymorphism and alpha-thalassaemia. The
      results also indicate that "normal" red cell values must be defined for each
      population where thalassaemias, G6PD deficiency and iron deficiency are common.

PMID- 7628586
TI  - Low serum levels of interleukin-6 in children with post-infective acute
      thrombocytopenic purpura.
AB  - Interleukin-6 plays an important role in host defense mechanisms and it appears
      to be a major mediator of the acute-phase response. IL-6 is also an important
      thrombocytopoietic factor. High serum levels of IL-6 are present in reactive
      thrombocytosis. The number and function of circulating platelets are the major
      factors that affect megakaryocytopoiesis by thrombopoietin. High levels of
      thrombopoietin have been observed in patients with thrombocytopenic purpura. To
      evaluate a possible thrombopoietin-like function of IL-6, we measured IL-6 levels
      in the serum of patients affected by post-infective acute thrombocytopenic
      purpura using a sensitive ELISSA assay. As controls, we studied normal subjects
      and patients with reactive thrombocytosis. No significant difference was observed
      between thrombocytopenic patients and normal controls. High IL-6 levels were
      present in patients with reactive thrombocytosis. In conclusion, we had not
      observed high levels of IL-6 in acute thrombocytopenic purpura and, very
      probably, IL-6 is not involved in the regulation of platelet mass for the
      hemostatic function. The thrombocytopoietic activity of IL-6 is another acute
      phase response and it is consistent with the other functions of this cytokine.
      This suggests an active participation of platelets in host defense mechanisms.

PMID- 7628585
TI  - Development of a criterion for response to therapy at 6 months in multiple
      myeloma.
AB  - To investigate the prognostic value of therapy at 6 months on survival in
      multiple myeloma, to develop a new criterion assessing response to initial
      therapy at 6 months, and to compare it to a current criterion. The types of
      initial and 6-month therapy were considered in a prognostic factor analysis in 70
      patients treated in routine practice. Using the response to initial therapy
      defined by the clinician's decision as grouping variable in this group, a
      discriminant analysis identified the characteristics of responder patients. The
      validity of the resulting criterion was tested in another test group. Its
      prognostic ability was compared to the CLMTF criterion (50% M-component reduction
      from baseline). The therapy at 6 months, reflecting the clinician's appraisal of
      response to initial therapy, predicted survival significantly. A criterion
      combining two variables (M-component change and haemoglobin level at 6 months)
      classified 70% and 72.4% of patients correctly regarding response status in the
      training and test groups respectively. This criterion was shown to perform better
      than the CLMTF criterion in predicting survival. CONCLUSION: A new criterion for
      response to therapy at 6 months, also presented in a nomogram, combines M
      component change and haemoglobin level at 6 months.

PMID- 7628587
TI  - Interleukin-4 inhibits the production of interleukin-1 by adult T-cell leukemia
      cells.
AB  - Freshly isolated leukemic cells from patients with adult T-cell leukemia (ATL)
      produce high levels of interleukin-1 (IL-1), which is believed to play an
      important role in neutrophilia, elevation of C-reactive protein, osteolytic bone
      lesions, hypercalcemia, and fever in ATL. However, relatively little is known
      regarding the regulatory mechanism of IL-1 production in ATL. Interleukin-4 (IL
      4) affects the monocytes- and neoplastic cells-mediated cytokine production. In
      this study, we investigated the effect of IL-4 on IL-1 alpha and IL-1 beta
      production by ATL cells in vitro. IL-4 was found to markedly inhibit the release
      of IL-1 alpha and IL-1 beta into the conditioned medium in a dose-dependent
      manner. Northern blot analysis of steady-state IL-1 mRNA demonstrated that IL-4
      treatment of ATL cells resulted in a reduction of IL-1 mRNA. These results
      support the notion that ATL cells spontaneously produce IL-1 alpha and IL-1 beta;
      however, such production can be inhibited by the immunomodulating agent, IL-4. IL
      4 may play an important regulatory role in the production of IL-1 in ATL.

PMID- 7628588
TI  - Reactive plasmacytosis and plasmacytic skin infiltration in a patient.

PMID- 7628589
TI  - Effectiveness of 2-chlorodeoxyadenosine in nodal and extra haematopoietic
      localizations in hairy cell leukaemia.

PMID- 7628590
TI  - Hodgkin's disease following extranodal non-Hodgkin's lymphoma.

PMID- 7628591
TI  - Myasthenia gravis following iron chelation therapy with intravenous
      desferrioxamine.

PMID- 7628592
TI  - Treatment of erythropoietin-resistant anaemia with desferrioxamine in patients on
      haemofiltration.
AB  - We studied 5 anaemic patients with Hb 74 +/- 8 g/l on haemofiltration (HF)
      treatment. They were iron overloaded. Their serum ferritin was 2667 +/- 8
      micrograms/l. All patients' haemoglobin (Hb) levels decreased after an initial
      response to recombinant human erythropoietin (r-HuEPO) treatment. An increase in
      r-HuEPO dose from 100 to 400 U/kg s.c. thrice weekly with addition of oral and
      intravenous iron treatment for 8 weeks arrested the fall in Hb level. However,
      there was no significant increase in Hb during these 8 weeks. Iron was withdrawn
      at week 24 and desferrioxamine (DFO) treatment (i.v. doses of 2 g thrice weekly)
      was added to r-HuEPO from week 26 to 36. Two weeks after DFO initiation the Hb
      level increased to 110 g/l. Thereafter the r-HuEPO doses were reduced from 400 to
      25 U/kg within 3 months. The Hb remained stable at a level of 110 g/l during the
      study, i.e., 17 months after the DFO treatment. Serum ferritin levels fell at a
      more rapid pace during DFO treatment and continued to decrease after DFO
      cessation for the following 17 months. In accordance with previous observations
      we found a positive effect of DFO treatment on erythropoiesis in patients with
      anaemia and iron overload. DFO treatment should be considered in patients with
      iron overload and r-HuEPO-resistant anaemia.

PMID- 7628593
TI  - Disseminated intravascular coagulation in acute leukaemias at first diagnosis.
AB  - Haemorrhagic diathesis is the commonest cause of morbidity and mortality in acute
      leukaemias (AL). It is most commonly due to thrombocytopenia resulting from bone
      marrow failure. However, in a significant number of cases, disseminated
      intravascular coagulation (DIC) plays an important part. Previously it was
      thought that this mechanism was mainly confined to acute promyelocytic leukaemia
      (APL), but recently it has also been reported to occur in other subtypes of acute
      leukaemia. We report the results of a study carried out to find the incidence of
      DIC in various types of AL at the time of first diagnosis and in the absence of
      other recognisable causes. DIC was observed in 14(13.4%) cases out of 104 cases
      of AL studied. Nine out of 49(18.4%) cases of AML and 5 out of 55(9.1%) cases of
      acute lymphoblastic leukaemia (ALL) showed coagulation abnormalities consistent
      with DIC. Out of the 9 cases of AML showing DIC, 63 (66.67%) belonged to APL (FAB
      ME) subtype. Three (60%) out of 5 cases of ALL with DIC had T-cell
      immunophenotype. The results indicate that DIC may also occur in types of AL
      other than APL, particularly in T-ALL, and should be looked for.

PMID- 7628594
TI  - In vitro drug sensitivity of leukemic progenitors and P-glycoprotein expression
      in adult acute myeloid leukemia: correlation with induction treatment outcome.
AB  - We have investigated the self-renewal capacity (PE2) and in vitro sensitivity to
      cytosine-arabinoside (ara-C) and daunorubicine (DNR) of leukemic progenitors (CFU
      AML) to determine the significance of these tests for predicting induction
      treatment outcome in 75 adult acute myeloid leukemia (AML) patients. In addition,
      in a part of this group of patients (n = 46) we determined the expression of P
      glycoprotein (P-gp) immunocytochemically and correlated those results with the
      therapeutic response. We have evaluated 66 patients who showed the following
      responses: 28/66 complete remissions (CR), 16/66 resistant leukemias (RL) and
      22/66 early deaths (ED). The PE2 value was significantly higher in patients with
      RL than in patients with CR (p < 0.00375). CFU-AML sensitivity to ara-C and DNR
      alone was not different between response groups, but the difference in CFU-AML
      sensitivity to the combination of drugs between patients with CR and RL was not
      significant, although a trend was noted (p < 0.06). P-gp expression was found in
      only 1/18 patients who achieved CR but in 9/11 patients with RL and 7/11 patients
      with ED, which is a highly significant difference (p < 0.0006). We concluded that
      both PE2 and P-gp expression in AML cells are valuable predictors of therapeutic
      response in adult AML and should be included in creating the best therapeutic
      approach to AML patients.

PMID- 7628595
TI  - Study of the role of vitamin B12 and folinic acid supplementation in preventing
      hematologic toxicity of zidovudine.
AB  - A prospective, randomized study was conducted to evaluate the role of vitamin B12
      and folinic acid supplementation in preventing zidovudine (ZDV)-induced bone
      marrow suppression. Seventy-five human immunodeficiency virus (HIV)-infected
      patients with CD4+ cell counts < 500/mm3 were randomized to receive either ZDV
      (500 mg daily) alone (group I, n = 38) or in combination with folinic acid (15 mg
      daily) and intramascular vitamin B12 (1000 micrograms monthly) (group II, n =
      37). Finally, 15 patients were excluded from the study (noncompliance 14, death
      1); thus, 60 patients (31 in group I and 29 in group II) were eligible for
      analysis. No significant differences between groups were found at enrollment.
      During the study, vitamin B12 and folate levels were significantly higher in
      group II patients; however, no differences in hemoglobin, hematocrit, mean
      corpuscular volume, and white-cell, neutrophil and platelet counts were observed
      between groups at 3, 6, 9 and 12 months. Severe hematologic toxicity (neutrophil
      count < 1000/mm3 and/or hemoglobin < 8 g/dl) occurred in 4 patients assigned to
      group I and 7 assigned to group II. There was no correlation between vitamin B12
      or folate levels and development of myelosuppression. Vitamin B12 and folinic
      acid supplementation of ZDV therapy does not seem useful in preventing or
      reducing ZDV-induced myelotoxicity in the overall treated population, although a
      beneficial effect in certain subgroups of patients cannot be excluded.

PMID- 7628596
TI  - Of families and other cultures: the shifting paradigm of family therapy.
AB  - This essay proposes that family therapy is currently undergoing a paradigm shift
      as a result of the ascendance of an epistemological focus absent in the
      foundational works that gave rise to the field's dominant clinical approaches.
      While systemic metaphors for the family are based on mechanistic, biological, and
      linguistic models primarily concerned with how the world is (ontology),
      postmodernism's social constructionist leanings give primacy to meaning,
      interpretation, and the intersubjectivity of knowledge (epistemology). Thus, the
      metaphor of the family as a system is gradually being subsumed by a metaphor that
      construes families as interpretive communities, or storying cultures. It is
      suggested that this largely implicit transformation be made explicit in order to
      explore more fully the clinical implications of the new epistemology.

PMID- 7628597
TI  - Association of interpersonal cognitive complexity with communication skill in
      marriage: moderating effects of marital distress.
AB  - Little research has examined the influence of social cognition on communicative
      behaviors that spouses exhibit in conversational interactions. The present study
      examined the associations between interpersonal cognitive complexity and three
      marital communication skills: communication effectiveness (generating messages
      that have the desired outcome), predictive accuracy (anticipating accurately the
      effects of a message on a receiver), and perceptual accuracy (correctly inferring
      the intent of a message source). The study also evaluated whether marital
      distress moderated associations between cognitive complexity and communication
      skills. Participants (60 couples) discussed a problem from their own marriage and
      a vignette from the Inventory of Marital Conflicts (Olson & Ryder, 1970) using
      the communication box. Cognitive complexity was moderately associated with
      perceptual accuracy, weakly associated with communication effectiveness, and not
      associated with predictive accuracy. Subsidiary analyses revealed that
      associations between cognitive complexity and the communication skills were
      generally stronger in the subsample of distressed couples than in the subsample
      of nondistressed couples.

PMID- 7628598
TI  - The nomothetic-idiographic debate in family therapy.
AB  - This essay introduces the terms "nomothetic" and "idiographic" to characterize
      the current debate about whether the field of family therapy should accumulate
      and apply knowledge about patterns of adjustment that hold across different
      families, or whether the field should consider each family as utterly unique, and
      should tailor interventions solely on the basis of these unique qualities.
      Embedded in this debate are the arguments for and against quantitative research,
      disagreements about the value of clinical prediction and interobserver
      reliability, as well as the issue of whether therapists can rightfully claim to
      possess "expert knowledge." The essay begins with the personal-professional
      anecdote that stimulated me to explore this debate in greater depth. It continues
      with a brief discussion of the historical context of this debate, particularly
      noting the parallels between the methodological issues in personality research
      and those facing family therapy. The nomothetic-idiographic debate in family
      therapy theory, research, and practice is then described. The essay ends with the
      suggestion that family therapy view nomothetic and idiographic thinking as
      complementary, and that the field strive to develop an integrated, "idiothetic"
      approach to family therapy research and practice.

PMID- 7628599
TI  - Integrating self and system: an empty intersection?
AB  - Synthesizing individual and family therapies can founder if the underlying
      epistemological assumptions concerning "what is self" are not taken into account.
      Most individual therapies assume self "really" exists as a relatively stable
      internal entity, the repository of residues of experience where traits, memories,
      et cetera are organized via internal schemas. Such a view tends to treat self as
      a thing, and implies that psychological problems are the result of internal
      deficits or conflicts; this can lead to difficulties in therapy. In contrast,
      ecosystemic views employ constructivist and contextualist approaches that are
      more fluid. However, by basing autopoetic self-organization in language,
      ecosystemic epistemology still separates subject from object. Adopting a
      perspective in which self has no fixed, distinguishing characteristics can
      resolve many difficulties and create a dimensionless point where self and system,
      individual and family, therapist and client can meet without hindrance.

PMID- 7628600
TI  - Creating a secure family base: some implications of attachment theory for family
      therapy.
AB  - The aim of this article is to make attachment research findings available in a
      form that family therapists can use. In attachment theory, parents are
      conceptualized as providing a secure base from which a child can explore. Family
      therapists, however, need a systemic concept that goes beyond the parent/child
      dyad. The concept of a secure family base is proposed, in which a network of care
      is made available for all family members of whatever age so that all family
      members feel secure enough to explore, in the knowledge that support is available
      if needed. Factors that contribute to the security or insecurity of the family
      base are outlined. The overall aim of therapy is to establish a secure family
      base from which the family can explore new solutions to family problems both
      during and after therapy. The role of the therapist is to help to resolve
      conflicts that threaten relationships, and to explore relevant belief systems
      that may be contributing to a sense of insecurity. The conceptual framework
      presented allows for an integration of family therapy techniques and ideas into a
      coherent whole. A new school of family therapy is not proposed.

PMID- 7628601
TI  - Dilution of family process in social services: implications for treatment of
      neglectful families.
AB  - Families identified as neglectful pose a special challenge to family therapists
      and other practitioners, not only because they are usually involuntary clients
      but also because of the relative weakness of their internal process, which often
      becomes "diluted" into the system of providers. Current social services practices
      that exacerbate the dilution of family process are hard to eradicate because they
      are rooted in a culture that promotes the transfer of functions from families to
      social agencies; families, immersed in the same culture, often collude with the
      agencies in their own dilution. The treatment of neglect in families calls for
      the nurturance of the family's process and the disruption of the complementary
      pattern between family and regulatory agencies.

PMID- 7628602
TI  - Rethinking boundary ambiguity from an ecological perspective: stress in
      Protestant clergy families.
AB  - Family researchers have virtually ignored the families of clergy as a population
      of interest. Their unique social ecology, however, can offer a profitable case
      study in family stress. The genesis of Boss's (1977, 1987) boundary ambiguity
      construct will be reviewed and critiqued. Bronfenbrenner's (1979) approach will
      then be applied to the boundary problems of clergy families. It is argued that an
      ecological analysis of boundary ambiguity in clergy families will lead to a
      higher-order understanding of the construct itself.

PMID- 7628603
TI  - The unencumbered child: family reputations and responsibilities in the care of
      relatives with Alzheimer's disease.
AB  - Using a grounded theory methodology in exploratory interviews with noncaregiving
      and caregiving adult children, differences were found in their experience of
      burden, their focus, their suffering, and their sense of responsibility.
      Childhood reputations appeared to follow siblings into adulthood, and they
      describe finding their adult positions in the family clearly circumscribed and
      entrenched because of family legacy. Children who were in some way different and
      excused from family responsibilities in childhood because they were, for example,
      "spoiled," a "problem child," the "intellectual," or "flaky," appeared to be
      unencumbered as adults when faced with caregiving responsibilities for a relative
      with Alzheimer's disease. Although these uninvolved and unencumbered children
      seemed to take less caregiving responsibility, they describe their loss and
      suffering in relation to a loss of identity and selfhood, whereas other children
      describe their burden and the overwhelming pulls and demands made on them. These
      preliminary findings suggest the need for systematic scientific inquiry about
      families, including multiple relatives, family history, impact of family-of
      origin legacy, family reputations, and family negotiation patterns.

PMID- 7628605
TI  - H2-forming N5,N10-methylenetetrahydromethanopterin dehydrogenase: mechanism of H2
      formation analyzed using hydrogen isotopes.
AB  - H2-forming N5,N10-methylenetetrahydromethanopterin dehydrogenase catalyzes the
      reversible dehydrogenation of N5,N10-methylenetetrahydromethanopterin (CH2 =
      H4MPT) to N5,N10-methenyltetrahydromethanopterin (CH = H4MPT+) and H2. In D2O
      both HD and D2 are formed from CH2 = H4MPT and in H2O both HD and H2 from CD2 =
      H4MPT. Evidence is presented that HD is not an intermediate in the formation of
      D2 and H2, respectively.

PMID- 7628604
TI  - The structure of porcine protegrin genes.
AB  - We cloned the genes of three protegrins, a family of cathelin-associated
      antimicrobial peptides originally isolated from porcine leukocytes. Each gene
      comprised 4 exons and 3 introns, wherein Exon I encoded the signal sequence and
      the first 37 amino acids of cathelin, Exons II and III contained 36 and 24
      additional cathelin residues and Exon IV contained the final two cathelin
      residues followed by the protegrin sequence. This quadripartite gene structure
      helps explain how structurally diverse antimicrobial peptides can be expressed on
      common, cathelin-containing precursors. Southern blot probed with an
      oligonucleotide specific for protegrin genes suggested that several identical or
      nearly identical protegrin genes were densely clustered in the pig chromosome.

PMID- 7628606
TI  - A minimum catalytic unit of F1-ATPase shows non-cooperative ATPase activity
      inherent in a single catalytic site with a Km 70 microM.
AB  - F1-ATPase has three interacting catalytic sites and shows complicated kinetics.
      Here, we report reconstitution of a complex, most likely composed of one alpha
      subunit and one beta subunit, with a single catalytic site from thermophilic
      Bacillus PS3 F1-ATPase on the solid surface. The complex has an ATPase activity
      which obeys a simple non-cooperative kinetics with a Km(ATP) of 70 microM and a
      Vmax of 0.1 unit/mg. Different from F1-ATPase, the complex is not inactivated by
      7-chrolo-4-nitrobenzofrazan. Thus, the inherent activity attributable to a single
      catalytic site unaffected by other catalytic sites of F1-ATPase is characterized.

PMID- 7628607
TI  - Site-directed mutants of the beta subunit of protein kinase CK2 demonstrate the
      important role of Pro-58.
AB  - The following amino acids of the Xenopus laevis beta subunit of protein kinase
      CK2 (casein kinase 2) were changed to alanine: Pro-58 (beta P-->A); Asp-59 and
      Glu-60 and Glu-61 (beta DEE-->AAA); His-151-153 (beta HHH-->AAA). The last 37
      amino acids of the carboxyl end were deleted (beta delta 179-215). Stimulation of
      CK2 alpha catalytic subunit activity was measured with casein as substrate and
      the following relative activities were observed: beta P-->A > beta DEE-->AAA >>>
      beta WT > beta HHH-->AAA >>> beta delta 179-215. The beta DEE-->AAA and beta P-
      >A were similar to beta WT in reducing CD2 alpha binding to DNA but beta delta
      179-215 was less active. The results indicate that both Pro-58 and the
      surrounding acidic cluster play roles in dampening the activation of CK2 alpha
      and that the carboxyl end of beta is involved in the interaction with CK2 alpha.

PMID- 7628608
TI  - Stimulation of cell proliferation and autoregulation of elastin expression by
      elastin peptide VPGVG in cultured chick vascular smooth muscle cells.
AB  - Synthetic elastin peptides, VPGVG or its polymer (VPGVG)n, enhanced the
      proliferation of smooth muscle cells 1.5-fold during 48 h treatment at the
      concentrations over 10(-6) M or 1.0 microgram/ml, respectively. Monomeric and
      polymeric VPGVG sequences reduced elastin synthesis and its mRNA level to one
      third and one-half of control respectively under the conditions in which the
      proliferation of cells were enhanced, but did not change collagen synthesis as
      measured by bacterial collagenase digestion. The elastin-specific autoregulation
      by elastin fragments may reflect the feedback regulation of elastin expression
      which may play an essential role in elastin metabolism under the normal and
      diseased conditions.

PMID- 7628609
TI  - Direct electrochemistry and EPR spectroscopy of spinach ferredoxin mutants with
      modified electron transfer properties.
AB  - Mutations of the conserved residue Glu-92 to lysine, glutamine, and alanine have
      been performed in the recombinant ferredoxin I of spinach leaves. The purified
      ferredoxin mutants were found twice as active with respect to wild-type protein
      in the NADPH-cytochrome c reductase reaction catalyzed by ferredoxin-NADP+
      reductase in the presence of ferredoxin. Cyclic voltammetry and EPR measurements
      showed that the mutations cause a change in the [2Fe-2S] cluster geometry, whose
      redox potential becomes approximately 80 mV less negative. These data point to a
      role of the Glu-92 side-chain in determining the low redox potential typical of
      the [2Fe-2S] cluster of chloroplast and cyanobacterial ferredoxins. Also a
      ferredoxin/ferredoxin-NADP+ reductase chimeric protein obtained by gene fusion
      was overproduced in Escherichia coli and purified. Fusion of the ferredoxin with
      its reductase causes only minor effects to the iron-sulfur cluster, as judged by
      cyclic voltammetry and EPR measurements.

PMID- 7628610
TI  - Plasma 8-epi-PGF2 alpha levels are elevated in individuals with non-insulin
      dependent diabetes mellitus.
AB  - This study reports plasma levels of a specific nonenzymatic peroxidation product
      of arachidonic acid, esterified 8-epi-PGF2 alpha, from healthy- and NIDDM
      individuals as an index of oxidative stress in vivo. Plasma 8-epi-PGF2 alpha was
      isolated by solid-phase extraction on a C18 followed by an NH2 cartridge and
      analyzed by GC-MS/NICI as PFB-ester/TMS-ether derivative. We found that the
      average concentration of esterified 8-epi-PGF2 alpha among NIDDM subjects (0.93
      +/- 0.07 nM, n = 39) was higher (P < 0.0001, Mann-Whitney test) than in healthy
      individuals (0.28 +/- 0.04 nM, n = 15). These data indicate that NIDDM is
      associated with increased plasma lipid peroxidation.

PMID- 7628611
TI  - Asn-265 of frog kainate binding protein is a functional glycosylation site:
      implications for the transmembrane topology of glutamate receptors.
AB  - Kainate binding proteins (KBPs) from frog and goldfish brain are glycosylated,
      integral membrane proteins. These KBPs are homologous (35-40%) to the C-terminal
      half of AMPA and kainate receptors which have been shown to form glutamate-gated
      ion channels. We report here that the frog KBP has three functional N
      glycosylation sites. Of particular interest, Asn-265, a residue located between
      two putative membrane spanning regions of the frog KBP, is a functional N
      glycosylation site. A mutation of Ser-267 to Gly renders this site non-functional
      as shown using an in vitro translation system and by transient expression in
      human embryonic kidney (HEK 293) cells. The mutant receptor protein (S267G), when
      expressed in HEK cells, binds kainate with high affinity (Kd = 16 nM). These
      results further support a topology with three transmembrane segments for KBPs
      and, by sequence homology, for glutamate-gated ion channels.

PMID- 7628612
TI  - The gamma subunit in the Escherichia coli ATP synthase complex (ECF1F0) extends
      through the stalk and contacts the c subunits of the F0 part.
AB  - A mutant, in which a cysteine has been site-directed into the polar loop region
      of the c subunit at residue 44, has been studied. Cross-linking of the c subunit
      to both the gamma and epsilon subunits was observed with cupric 1,10
      phenanthrolinate treatment. The linkage between the c and gamma subunits was
      localized to that part of the gamma subunit between residues 202-286, based on
      peptide analysis. Reference to the high resolution structure of F1 [Abrahams et
      al. (1994) Nature 370, 621-628] appears to limit this contact site to the region
      including residues 202-230. This segment contains 4 tyrosines and 1 tryptophan as
      possible reactive residues for cross-linking with the c subunit cysteine.

PMID- 7628613
TI  - Induction of the antioxidant stress proteins heme oxygenase-1 and MSP23 by stress
      agents and oxidised LDL in cultured vascular smooth muscle cells.
AB  - Enhanced expression of the antioxidant stress proteins heme oxygenase-1 (HO-1)
      and macrophage stress protein (MSP23) by oxidative stress agents and oxidatively
      modified low density lipoproteins (LDL) was investigated in cultured porcine
      aortic smooth muscle cells. Treatment of smooth muscle cells with glucose
      oxidase, CdCl2 or diethylmaleate resulted in a time-dependent (6-48 h) induction
      of HO-1 and MSP23 expression. Exposure of cells to 100 micrograms protein/ml
      highly oxidised LDL increased the expression of HO-1 and MSP23 within 24 h, and
      the induction was dependent on the degree of LDL oxidation. The induction of HO-1
      and MSP23 may thus play an important cytoprotective role against oxidative stress
      in atherogenesis.

PMID- 7628614
TI  - Isolation and complete amino acid sequence of the beta- and alpha-polypeptides
      from the peripheral light-harvesting pigment-protein complex II of Rhodobacter
      sulfidophilus.
AB  - The peripheral light-harvesting bacteriochlorophyll-carotenoid-protein complex
      B800-850 (LHII) has been isolated from membranes of semi-aerobic dark-grown cells
      of Rhodobacter sulfidophilus strain W4. A reversed-phase HPLC system resolved one
      beta- and one alpha-polypeptide in the ratio 1:1. The material obtained was of
      high purity and suitable for direct microsequence analysis. The primary
      structures of the beta- and alpha-polypeptides have been determined. The beta
      polypeptide consists of 51 amino acid residues, yielding a molecular mass of 5512
      Da and having 64.7% hydrophobicity. The alpha-polypeptide consists of 52 amino
      acid residues, with a calculated molecular mass of 5661 Da and 75%
      hydrophobicity. The significance of uncommon structure motives with respect to
      the unusual spectroscopic characteristics of this light-harvesting complex is
      discussed.

PMID- 7628615
TI  - Adenophostin-medicated quantal Ca2+ release in the purified and reconstituted
      inositol 1,4,5-trisphosphate receptor type 1.
AB  - Kinetics of Ca2+ release by adenophostin, a novel agonist of inositol 1,4,5
      trisphosphate (IP3) receptor, in the purified and reconstituted IP3 receptor type
      1 (IP3R1) was investigated using the fluorescent Ca2+ indicator fluo-3.
      Submaximal concentrations of adenophostin caused quantal Ca2+ release from the
      purified IP3R1 as IP3 did. Adenophostin-induced Ca2+ release by the purified
      IP3R1 exhibited a high positive cooperativity (nH = 3.9 +/- 0.2, EC50 = 11 nM),
      whereas the IP3-induced Ca2+ release exhibited a moderate one (nH = 1.8 +/- 0.1,
      EC50 = 100 nM). Inhibition of [3H]IP3 binding to the purified IP3R1 by
      adenophostin exhibited a positive cooperativity (nH = 1.9, Ki = 10 nM), whereas
      IP3 did not (nH = 1.1, Ki = 41 nM).

PMID- 7628616
TI  - Proton coupling is preserved in membrane-bound chloroplast ATPase activated by
      high concentrations of tentoxin.
AB  - The effect of tentoxin at high concentrations was investigated in thylakoids and
      proteoliposomes containing bacteriorhodopsin and CF0CF1. Venturicidin-sensitive
      ATP hydrolysis, ATP-generated delta pH and ATP synthesis were practically 100%
      inhibited at 2 microM tentoxin, and restored to various extents beyond 50 microM.
      With respect to the native enzyme, tentoxin-reactivated ATPase had the following
      properties: (i) a higher delta pH requirement to synthetise ATP; (ii) a decreased
      futile proton flow through CF0CF1 (without ADP), which remains 100% blocked by
      ADP. It is concluded that despite its altered kinetic performances, tentoxin
      modified CF0CF1 preserves its mechanism and remains a tightly coupled proton
      pump.

PMID- 7628617
TI  - Isolation and characterisation of plant defensins from seeds of Asteraceae,
      Fabaceae, Hippocastanaceae and Saxifragaceae.
AB  - From seeds of Aesculus hippocastanum, Clitoria ternatea, Dahlia merckii and
      Heuchera sanguinea five antifungal proteins were isolated and shown to be
      homologous to plant defensins previously characterised from radish seeds and
      gamma-thionins from Poaceae seeds. Based on the spectrum of their antimicrobial
      activity and the morphological distortions they induce on fungi the peptides can
      be divided into two classes. The peptides did not inhibit any of three different
      alpha-amylases.

PMID- 7628618
TI  - Evidence for SecA- and delta pH-independent insertion of D1 into thylakoids.
AB  - Many nuclear-encoded proteins are targeted into chloroplast thylakoids by an
      azide sensitive Sec-related mechanism or by a delta pH-driven mechanism. In this
      report, the requirements for the integration of chloroplast-encoded thylakoid
      proteins have been analysed in pulse-labeled intact chloroplasts. We show that
      the integration of the photosystem II reaction centre protein, D1, continues in
      the absence of a delta pH and in the presence of azide. A range of other proteins
      are similarly targeted to thylakoids in the presence of azide, suggesting that
      the SecA-related mechanism is not widely used for the targeting of chloroplast
      encoded proteins.

PMID- 7628619
TI  - Diffuse vesicular distribution of Rab3D in the polarized neuroendocrine cell line
      AtT-20.
AB  - The neuroendocrine cell line AtT-20 has two types of storage vesicles: dense core
      granules and synaptic vesicles, both sequestered at the tip of the processes.
      Here we show that Rab3D protein, which is abundant in fat cells, is also
      expressed in AtT-20 cells. Differently from Rab3A, which is localized in
      secretory vesicles accumulated at the tips, Rab3D has a diffuse vesicular
      distribution in the cytoplasm of the cell body, the processes and the tips. In
      AtT-20 cells, Rab3D may define a regulated secretory pathway which functions
      independently from cell polarity.

PMID- 7628620
TI  - Functional characterization of the promoter region of the mouse protein kinase C
      gamma gene.
AB  - Promoter activity of protein kinase C (PKC) gamma gene was analysed by
      chloramphenicol acetyltransferase (CAT) assay using extracts from the cells
      transfected with various fusion constructs containing the 5'-flanking region of
      the mouse PKC gamma gene and CAT gene. Transient expression experiments in PC12
      cells revealed that the upstream region of 87 bp from the transcriptional
      initiation site was sufficient for promoter activity. The region containing
      nucleotides 87 upstream from the transcriptional initiation site was shown to
      silence CAT activity in Balb/c3T3 cells, in which mRNA of PKC gamma was not
      detected, suggesting that this region might contain a transcriptional regulatory
      element for the cell type-specific expression of the PKC gamma gene.

PMID- 7628621
TI  - 1H NMR T1 relaxation rate study on substrate orientation of fluoromethylanilines
      in the active sites of microsomal and purified cytochromes P450 1A1 and 2B1.
AB  - The present study describes 1H NMR T1 relaxation rate studies on
      fluoromethylanilines bound to the active sites of microsomal and purified
      cytochromes P450 1A1 and 2B1. From the data obtained, insights into the average
      orientation of the substrates with respect to the paramagnetic Fe3+ centre in the
      cytochromes P450 could be derived. Particular attention was paid to a possible
      extra relaxation pathway for methyl protons compared to the aromatic protons, due
      to the rotational motion of the CH3 around the sigma-C-CH3 bond. However, this
      effect appeared to be minimal and to result in at most a few percent
      underestimation of the actual distance of the methyl protons to the Fe3+ centre.
      Furthermore, the data obtained demonstrate that all aromatic protons are at about
      the same average distance from the paramagnetic centre. The results also
      demonstrate that the fluromethylanilines are bound to the active sites of
      cytochromes P450 1A1 and 2B1 in a similar way. A time-averaged orientation of the
      substrate with the Fe3+ above the aromatic ring, with the pi-orbitals of the
      aromatic ring and those of the porphyrin rings in a parallel position, providing
      possibilities for energetically favourable pi-pi interaction defines the
      orientation which best fits the results of the present study. Possibilities for a
      flip-flop rotation around an axis in the plane of the aromatic ring can be
      included in this picture, as such rotations would still result in a similar
      average distance of all aromatic protons to the Fe3+ paramagnetic centre. The
      results obtained also indicate that possible differences in metabolite patterns
      resulting from conversion of the fluoromethylanilines by different cytochromes
      P450, especially P450 1A1 and 2B1, are unlikely to be caused by a specific
      orientation of the substrate imposed by the substrate binding site of the enzyme.

PMID- 7628622
TI  - ESR studies on the effect of ionic radii on displacement of Mn2+ bound to a
      soluble beta-galactoside binding hepatic lectin.
AB  - Binding of divalent metal ions to hepatic soluble beta-galactoside binding lectin
      was studied using electron spin resonance (ESR) spectroscopy. The Mn2+ bound to
      hepatic lectin could be displaced by Mg2+, Cu2+, Ni2+ and Ca2+ but not by Sr2+.
      As the ionic radii of Mg2+ (0.65 A), Cu2+ (0.73 A) and Ni2+ (0.72 A) are
      appreciably smaller than Ca2+ (0.99 A), it appears that the Mn2+ binding site is
      more accessible to Mg2+, Cu2+, and Ni2+ as compared to Ca2+, the ionic radius of
      Mn2+ being 0.80 A. Sr2+ with an ionic radius of 1.13 is thus unable to displace
      bound Mn2+. Surprisingly, the presence of specific sugars like alpha-lactose, or
      alpha-D-galactose facilitated the displacement of bound Mn2+ by metal ions
      whereas non-specific sugars, i.e. alpha-D-glucose, beta-D-fructose and alpha-D
      ribose had no effect. It appears that minor perturbations in the saccharide
      binding site significantly affect the ability of the metal binding site to ligate
      bivalent metals.

PMID- 7628623
TI  - The three-dimensional structure of thymidine kinase from herpes simplex virus
      type 1.
AB  - Recombinant thymidine kinase from Herpes simplex virus type 1 (ATP:thymidine 5'
      phosphotransferase; EC 2.7.1.21), an enzyme of therapeutic importance, was
      purified and crystallized in an N-terminally truncated but still fully active
      form. The three-dimensional structure was solved by X-ray diffraction analysis at
      3.0 A resolution using isomorphous replacement. The chain fold is presented
      together with the bound substrates thymidine and ATP. Three chain segments at the
      surface could not be located. The chain fold, the location of the substrates and
      presumbly also the catalytic mechanism resemble the well-known adenylate kinases.

PMID- 7628624
TI  - In vitro dissociation and re-assembly of peroxisomal alcohol oxidases of
      Hansenula polymorpha and Pichia pastoris.
AB  - We have studied the in vitro inactivation/dissociation and subsequent
      reactivation/re-assembly of peroxisomal alcohol oxidases (AO) from the yeasts
      Hansenula polymorpha and Pichia pastoris. Both proteins are homo-oligomers
      consisting of eight identical subunits, each containing one FAD as the prosthetic
      group. They were both rapidly inactivated upon incubation in 80% glycerol, due to
      their dissociation into the constituting subunits, which however still contained
      FAD. Dilution of dissociated AO in neutral buffer lead to reactivation of the
      protein due to AO re-assembly, as was demonstrated by non-denaturing PAGE. After
      use of mixtures of purified AO from H. polymorpha and P. pastoris active hybrid
      AO oligomers were formed. When prior to dissociation FAD was chemically removed
      from AO, reactivation or re-assembly did not occur independent of externally
      added FAD.

PMID- 7628625
TI  - Ras binding to a C-terminal region of GAP.
AB  - Using fluorescence spectroscopy we have identified a binding region for Ras on
      the GTPase activating protein (GAP) lying within residues 715-753. A synthetic
      peptide Y922, corresponding to residues 716-753 of GAP binds to wild type Ras
      showing 3.3-fold higher affinity for the GTP- over the GDP-bound forms of Ras.
      Binding is stabilised by Mg2+, although Y922 does not stimulate the GTPase
      activity of Ras. Peptide binding to the Y32A and Y40F Ras mutants showed equal
      affinity for both GDP- and GTP-bound forms, with binding to Y32A.GDP abolished in
      the absence of Mg2+. These results suggest that Y922 mimics the in vivo
      interactions shown by the intact p120GAP protein and provide the first direct
      demonstration of Ras interaction with GAP in the region 715-753.

PMID- 7628626
TI  - Extraordinary enhancement of the cleavage activity of a DNA-armed hammerhead
      ribozyme at elevated concentrations of Mg2+ ions.
AB  - As part of an ongoing effort to characterize structure-function relationships,
      activities of all-RNA and DNA-armed hammerhead ribozymes were examined. An
      analysis of the dependence on the concentration of Mg2+ ions of cleavage rates
      revealed that, whereas the kcat of the reaction catalyzed by the all-RNA ribozyme
      reached a maximum value of about 18 min-1 at a concentration of about 200 mM Mg2+
      ions, that of the DNA-armed ribozyme increased linearly as the concentration of
      Mg2+ ions was increased above 300 mM, finally reaching a value of more than 100
      min-1 at 700 mM Mg2+ ions. These results suggest that the potential activity of a
      hammerhead ribozyme might be greater than is usually recognized.

PMID- 7628627
TI  - Tendon extracellular matrix contains pentameric thrombospondin-4 (TSP-4).
AB  - In preparations of cartilage oligomeric matrix protein (COMP) from bovine tendon
      two contaminating polypeptides of 120 and 135 kDa were detected. N-terminal
      protein sequencing of these polypeptides showed homology to the N-terminus and to
      an internal sequence in TSP-4, respectively. TSP-4 was further enriched by
      heparin affinity chromatography. Electron microscopy of this sample shows
      primarily five armed particles with globular domains at the periphery connected
      to a central assembly domain in which smaller N-terminal globular domains can be
      resolved tightly packed at the center of the particle. We can thereby confirm the
      pentameric model for TSP-4 proposed by Lawler et al. [(1995) J. Biol. Chem. 270,
      2809-2814], on the basis of recombinantly expressed protein. We further show that
      TSP-4 is abundant in tendon.

PMID- 7628628
TI  - Promoter-specific regulation of gene expression by an exogenously added
      homedomain that promotes neurite growth.
AB  - pAntp, a 60 amino acid long peptide corresponding to the homeodomain of the
      Drosophila Antennapedia protein, translocates through neuronal membranes when
      added exogenously to neurons in culture, where it accumulates in the nucleus and
      promotes neurite outgrowth. We proposed that the peptide, once internalized, may
      compete for homeoprotein DNA binding sites. To investigate this point, we have
      produced a permanent fibroblast cell line which carries a luciferase reporter
      gene under the control of a 93 bp genomic region of the HOXD9 promoter with
      binding sites for homeoproteins. Externally added pAntp specifically down
      regulates the expression of the reporter gene, suggesting that the neurotrophic
      effects observed previously are mediated by direct binding of pAntp to
      homeoprotein target sites.

PMID- 7628629
TI  - Recognition of 2'-hydroxyl groups by Escherichia coli ribonuclease HI.
AB  - In order to investigate the hydrogen-bonding interactions between Escherichia
      coli ribonuclease HI and the 2'-hydroxyl functions of the substrate,
      oligonucleotide duplexes containing 2'-amino-2'-deoxyuridine or 2'-fluoro-2'
      deoxyuridine at a specific site were used, and their affinities for the enzyme
      were determined by kinetic analyses. The results indicate that the hydroxyl
      groups of the nucleoside 3'-adjacent to the cleaved phosphodiester linkage and
      the second nucleoside 5' to the cleaved phosphodiester act as both a proton donor
      and an acceptor and as a proton acceptor, respectively, in the enzyme-substrate
      complex. A molecular model was constructed using the interactions derived from
      the results.

PMID- 7628630
TI  - Characterization of the interaction of Raf-1 with ras p21 or 14-3-3 protein in
      intact cells.
AB  - Several deletion mutants of Raf-1 were expressed with v-ras p21 or 14-3-3 protein
      in COS-7 cells and Sf9 cells and the interaction of Raf-1 with ras p21 or with 14
      3-3 protein in intact cells was examined. Raf(1-135) (residues 1-135) and Raf(1
      322) interacted with v-ras p21, but other deletion mutants such as Raf(136-322)
      or Raf(321-648) did not. Raf(1-322) interacted with 14-3-3 protein much more
      efficiently than Raf(321-648) did. While Raf(1-135) did not interact with 14-3-3
      protein, Raf(136-322) did. These results clearly indicate that Raf-1
      simultaneously interacts with both ras p21 and 14-3-3 protein through the
      distinct binding domains in intact cells.

PMID- 7628631
TI  - Resistant P45051A1 activity in azole antifungal tolerant Cryptococcus neoformans
      from AIDS patients.
AB  - Azole antifungal compounds are important in the treatment of Cryptococcosis, a
      major cause of mortality in AIDS patients. The target of the azole drugs is P450
      mediated sterol 14 alpha-demethylase. We have investigated the P450 system of
      Cryptococcus neoformans with respect to azole tolerance observed in clinical
      isolates which were obtained following the failure of fluconazole therapy. The
      clinical failure was correlated with in vitro tolerance of azole antifungal when
      compared to wild-type strains. The microsomal P450 system was typical of yeast
      and fungi and fluconazole tolerance was not associated with defective sterol
      biosynthesis. The strains had slightly elevated P450 content and slightly reduced
      azole levels in the cells, but a clear cause for resistance was the increased
      level of drug needed to inhibit the sterol 14 alpha-demethylase in vitro.

PMID- 7628632
TI  - hBD-1: a novel beta-defensin from human plasma.
AB  - We report the isolation and characterization of a novel peptide with significant
      sequence homology to beta-defensins from human blood filtrate. The human beta
      defensin-1 (hBD-1) is a short basic peptide of 36 amino acid residues. It
      contains six cysteines forming three intramolecular disulfide bonds. The
      molecular mass of hBD-1 is 3928.6 Da. Cloning of the specific cDNA confirmed the
      amino acid sequence of the native peptide. hBD-1 shares the nine conserved amino
      acids characteristic for beta-defensins from respiratory epithelial cells and
      neutrophils of cattle and chicken leukocytes. hBD-1 is present in nanomolar
      concentration in human plasma.

PMID- 7628633
TI  - A role for active oxygen species as second messengers in the induction of
      alternative oxidase gene expression in Petunia hybrida cells.
AB  - Incubation of Petunia hybrida cells with H2O2 leads to an increase in alternative
      oxidase activity measured after 24 h. This increased activity is accompanied by
      an increase in alternative oxidase protein. A model is presented for the
      regulation of alternative oxidase protein synthesis in which active oxygen
      species and especially H2O2 play a crucial role as second messengers in the
      signal transducing pathway from the mitochondria to the nucleus. It is proposed
      that also the induction of the alternative oxidase by salicylic acid is mediated
      via H2O2.

PMID- 7628634
TI  - Angiotensin II transduces its signal to focal adhesions via angiotensin II type 1
      receptors in vascular smooth muscle cells.
AB  - In cultured vascular smooth muscle cells (VSMCs), angiotensin II (Ang II)
      stimulated tyrosine phosphorylation of several proteins including a cluster of 70
      80-kDa proteins as assessed by anti-phosphotyrosine immunoblotting. These 70-80
      kDa proteins were identified as a focal adhesion-associated protein, paxillin, by
      anti-paxillin immunoprecipitation. Ang II-stimulated tyrosine phosphorylation of
      paxillin was detectable within 1 min and maximal at around 10 min and was
      concentration dependent (half-maximal effect at around 1 nM). Ang II also
      stimulated tyrosine phosphorylation of focal adhesion kinase in a time- and
      concentration-dependent manner. The Ang II type 1 (AT1) receptor antagonist, CV
      11974, but not the Ang II type 2 receptor antagonist, PD123319, inhibited these
      reactions. These results indicate that Ang II transduces its signal to focal
      adhesions via AT1 receptors in cultured VSMCs.

PMID- 7628635
TI  - Induction of p53 and apoptosis by delta 12-PGJ2 in human hepatocarcinoma SK-HEP-1
      cells.
AB  - Human hepatocarcinoma cells (SK-HEP-1) were induced to die through apoptosis by
      treatment with delta 12-prostaglandin (PG)J2, as characterized by the appearance
      of a typical DNA ladder. The induction of apoptosis by delta 12-PGJ2 was
      specifically blocked by cycloheximide (CHX). Western analysis using anti-p53 or
      anti-WAF1 monoclonal antibodies demonstrated that these two protein levels were
      increased 3 h after delta 12-PGJ2 treatment, and accumulated for up to 12 h. The
      induction of p53 protein seemed to be dependent on the increase of p53 mRNA
      level, which was inhibited by CHX treatment. However, delayed addition of CHX
      after delta 12-PGJ2 treatment failed to affect both p53 mRNA levels and DNA
      fragmentation following delta 12-PGJ2 treatment, indicating that the inhibition
      of p53 synthesis may contribute to the protective effect of CHX against delta 12
      PGJ2-mediated cytotoxicity. Therefore, our results suggest that the initial
      events caused by delta 12-PGJ2, leading ultimately to SK-HEP-1 cell death,
      involve a certain process required for p53 induction. However, the finding that
      delta 12-PGJ2 is also active against Hep 3B cells which are devoid of a
      functional p53 indicates that p53 may not be the critical requirement for
      inducing apoptosis by delta 12-PGJ2.

PMID- 7628636
TI  - Characterisation of the Sek-1 receptor tyrosine kinase.
AB  - We present an initial characterisation of the mouse Sek-1 protein, a member of
      the Eph subfamily of putative receptor tyrosine kinases, which has been proposed
      to play a role in the segmentation of both the hindbrain and the mesoderm.
      Antibodies raised against the protein have been used to confirm the early
      embryonic expression pattern previously established by mRNA in situ
      hybridisation. These antibodies, together with the expression of the Sek-1 gene
      in a baculovirus system, were instrumental in demonstrating that the protein
      carries a tyrosine kinase activity and that it is presented at the cell surface
      with its N-terminal (putative ligand-binding) domain outside of the cell.
      Therefore, as expected from its amino acid sequence, Sek-1 conforms to the
      general model of receptor-type tyrosine kinases.

PMID- 7628637
TI  - Localization of cyclic-AMP receptors with acidosomes in Dictyostelium discoideum.
AB  - Earlier studies have shown that in Dictyostelium discoideum, a buoyant membrane
      fraction contained approximately 90% of the vacuolar proton pump (V-H(+)-ATPase)
      activity, leading to its designation acidosomes. It was proposed that acidosomes
      may be involved in endocytosis, specially in the acidification of endosomes. In
      this study we further investigated the putative function(s) of acidosomes. The
      findings suggest that acidosomes contain abundant receptors for cyclic AMP (CAR1)
      and that it may be the site for recycling of internalized receptors. Acidosomes
      also contain an abundance of Rab4 (Bush et al. 1994), a marker for early
      endosomes. By these criteria, we suggest that the acidosomes are analogous to
      early or recycling endosome present in mammalian cells. These findings suggest
      that the structure earlier defined biochemically, morphologically and
      immunologically as acidosomes may represent early and/or recycling endosomes in
      this protist.

PMID- 7628639
TI  - Effects of delta-sleep inducing peptide (DSIP) and some analogues on the activity
      of monoamine oxidase type A in rat brain under hypoxia stress.
AB  - Metabolic effects of delta-sleep inducing peptide (DSIP) under hypoxia stress
      were investigated in rats subjected to short-term hypoxic conditions (about 0.26
      Bar). It was found that DSIP partially restricted stress-induced changes in
      activity of mitochondrial monoamine oxidase type A (MAO-A) and serotonin level in
      rat brain. A number of DSIP analogues was tested and among them there were some
      compounds with enhanced ability to counteract hypoxia induced changes in MAO-A
      activity and serotonin content in comparison with native neuropeptide.

PMID- 7628638
TI  - Two-dimensional gel mapping of the processing of the human amyloid precursor
      protein in rat hippocampal neurons.
AB  - The proteolytic fragments derived from the amyloid precursor protein (APP) in
      primary cultures of rat hippocampal neurons were analyzed by two-dimensional gel
      electrophoresis. The Semliki Forest Virus expression vector was used to express
      human APP695 and a mutant form associated with familial Alzheimer's disease (APP
      FAD670/671). Hippocampal neurons expressing wtAPP695 or APP-FAD670/671 secrete at
      least six APP fragments of 100-110 kDa with isoelectric focusing points ranging
      from 4.5 to 4.0. The heterogeneity of the secreted APP forms is shown to be in
      part due to differences in glycosylation. In contrast to wtAPP695, neurons
      producing the APP-FAD670/671 variant did not secrete detectable amounts of
      secretory APP derived from cleavage within the amyloid beta A4 domain. This
      result suggests that there is little alpha-secretase cleavage in neurons
      expressing the APP-FAD670/671 mutant.

PMID- 7628640
TI  - Excitation delocalization over the whole core antenna of photosynthetic purple
      bacteria evidenced by non-linear pump-probe spectroscopy.
AB  - Anomalously high values of photoinduced absorption changes were revealed in the
      antenna of photosynthetic purple bacteria. They were found to be 4-16 times
      greater at the bleaching peak of the antenna than at the bleaching peak of the
      BChl dimer of the reaction center. This is direct proof of excitation
      delocalization over many pigment molecules. Calculations according to the model
      of exciton delocalization over all core antenna BChls allow one to explain the
      observed phenomenon.

PMID- 7628641
TI  - Cell-specific effects of RAS oncogene and protein kinase C agonist TPA on P
      glycoprotein function.
AB  - We compared the influence of exogenous N-ras oncogene and treatment with PKC
      agonist 12-O-tetradecanoylphorbol-13-acetate (TPA) on P-glycoprotein (Pgp)
      function in various human, rat and dog cell lines. Two approaches were used: (a)
      flow cytometry analysis of Rhodamine 123 (Rh123) exclusion; and (b) sensitivity
      to cytotoxic action of colchicine. We have found that in Rat1 fibroblasts, rat
      IAR2 epithelial cells and rat McA RH 7777 (hepatoma), ras activates Pgp function,
      while in MDCK (dog kidney), K562 (human chronic myelogenous leukaemia) and
      LIM1215 (human colon carcinoma) cells it either has no effect or even acts in
      opposite direction. TPA-induced Pgp function shows dissimilar pattern of cell
      specificity. It is assumed that PKC and ras oncogene regulate mdr1 gene
      expression through at least partially distinct signalling pathways.

PMID- 7628642
TI  - Phenylarsine oxide inhibits tyrosine phosphorylation of phospholipase C gamma 2
      in human platelets and phospholipase C gamma 1 in NIH-3T3 fibroblasts.
AB  - The sulphydryl reagent phenylarsine oxide (PAO) (1 microM) inhibited completely
      formation of inositol phosphates in human platelets induced by collagen or by
      cross-linking of the platelet low affinity Fc receptor, F c gamma RIIA, but did
      not alter the response to the G protein receptor agonist thrombin. PAO also
      inhibited completely tyrosine phosphorylation of PLC gamma 2 in collagen and Fc
      gamma RIIA-stimulated cells, although tyrosine phosphorylation of other proteins
      including the tyrosine kinase syk was relatively unaffected. PAO (1 microM) also
      inhibited completely tyrosine phosphorylation of PLC gamma 1 induced by platelet
      derived growth factor (PDGF) in NIH-3T3 fibroblasts but only partially reduced
      phosphorylation of the PDGF receptor. These results provide further evidence that
      collagen and Fc gamma RIIA cross-linking activate platelets through a pathway
      distinct from that used by thrombin and suggest that PAO may be a selective
      inhibitor of PLC gamma relative to PLC beta isozymes.

PMID- 7628643
TI  - cAMP-dependent protein kinase activity is essential for preaggregative gene
      expression in Dictyostelium.
AB  - Constitutive inhibition of cAMP-dependent protein kinase (PKA) in Dictyostelium
      cells blocks cell aggregation and development. We investigated the cause of the
      aggregation defect in transformants overexpressing dominant-negative PKA
      regulatory subunits (PKA-RM) under an actin 15 promoter. These mutants could not
      relay pulses of the chemoattractant cAMP, due to a defect in expression of the
      aggregative adenylyl cyclase (ACA) gene. Unstimulated and cAMP pulse-induced
      expression of other aggregative genes encoding the cAMP receptor cAR1, adhesive
      contact sites A and cAMP-phosphodiesterase were also strongly reduced in the
      mutants. Additionally, the expression of the discoidin I gene, that is expressed
      early in development in response to cell density sensing factors, was almost
      completely absent. These data are in interesting contrast with observations that
      cAMP relay and aggregative gene expression are normal in null mutants for the PKA
      catalytic (C) subunit and suggest the presence of multiple C subunit genes in
      Dictyostelium and an almost universal requirement for PKA activity in
      developmental gene expression.

PMID- 7628644
TI  - ATP-dependent efflux of calcein by the multidrug resistance protein (MRP): no
      inhibition by intracellular glutathione depletion.
AB  - In this study we report that the multidrug resistance protein (MRP) transports
      calcein from the cytoplasmic compartment of tumor cells, in contrast to P
      glycoprotein which transports calcein acetoxymethyl ester from the
      plasmamembrane. The transport of calcein by MRP is ATP-dependent and is inhibited
      by probenecid and vincristine. Intracellular glutathione (GSH) depletion which
      occurred when cells were exposed to buthionine sulfoximine had no effect on the
      efflux of calcein, whereas it reversed the daunorubicin accumulation deficit in
      MRP overexpressing tumor cells. In conclusion, ATP-dependent transport of calcein
      and possibly other organic anions by MRP is not inhibited by a large decrease of
      the intracellular GSH concentration, that inhibits daunorubicin efflux by MRP.

PMID- 7628645
TI  - Oligomeric structure of a renal cystine transporter: implications in cystinuria.
AB  - Homologous proteins (NBAT) which mediate sodium-independent transport of neutral
      as well as basic amino acids and cystine when expressed in Xenopus oocytes were
      recently cloned from mammalian kidneys. Mutations in human NBAT have been
      implicated in cystinuria. Here, we show that rat kidney and jejunal brush border
      membrane NBAT (85 kDa) is found in association with a 50 kDa protein. The
      association involves one or more interprotein disulfide bonds. Rabbit kidney
      brush border membranes and membranes of NBAT cRNA-injected Xenopus oocytes also
      contain such heterodimers. Our data suggest that the heterodimer is the minimal
      functional unit of NBAT-mediated amino acid transport and that the NBAT
      associated 50 kDa protein could play a role in cystinuria.

PMID- 7628646
TI  - Sphingomyelin is synthesized at the plasma membrane of oligodendrocytes and by
      purified myelin membranes: a study with fluorescent- and radio-labelled ceramide
      analogues.
AB  - In most cell types sphingomyelin is synthesized predominantly in the cis-medial
      compartments of the Golgi stacks whereas the contribution of the plasma membrane
      is much lower. The aim of this study was to assess the contribution of both
      compartments to the synthesis of sphingomyelin in myelinating cells. Therefore,
      oligodendrocytes from rat spinal cord were incubated in culture with
      fluorescently- or radiolabelled ceramides, and the effects of a block in the
      vesicular flow (monensin, brefeldin A, low temperature) on surface synthesis of
      sphingomyelin were evaluated. The results indicate that approximately 50% of the
      sphingomyelin synthase is present at the plasma and myelin membranes of
      oligodendrocytes.

PMID- 7628647
TI  - Increasing generalist production.

PMID- 7628648
TI  - Should family medicine courses be graded or given pass/fail marks?

PMID- 7628649
TI  - The Cochrane Collaboration in Primary Care: an international resource for
      evidence-based practice of family medicine.
AB  - In recent years, promoting the use of evidence-based decision making in health
      care has been gaining popularity. This method of decision making requires that
      the results of primary research be compiled in a systematic manner and made
      accessible to those involved in the decision-making process. Failure to do this
      may result in a considerable lag period before therapies of proven effectiveness
      are implemented in medical practice or ineffective therapies are withdrawn from
      practice. The Cochrane Collaboration in Primary Health Care was established as
      part of an international effort to facilitate the preparation, maintenance, and
      dissemination of systematic reviews of the effects of health care provided in, or
      relevant to family practice. This paper describes the progress made in
      establishing the Cochrane Collaboration as an international register of
      randomized controlled trials in family medicine that will subsequently be used
      for undertaking systematic reviews in the discipline.

PMID- 7628650
TI  - Translating family medicine's educational expertise into academic success.
AB  - BACKGROUND: Today's family medicine educator occupies a position of increasing
      stature in medical education. The recognition of education as scholarship creates
      a framework for the evaluation of clinician-educators for promotion. A system is
      needed to document educational excellence, peer review, and public dissemination.
      METHODS: The Educator's Portfolio, a 10-category system for organizing
      educational expertise, was developed in a family medicine department for use as a
      promotion document. The effectiveness of the Educator's Portfolio in documenting
      faculty candidates' educational activities was assessed in two ways. Members of
      the department rank and tenure committee were surveyed to assess their ability to
      evaluate faculty teaching contributions using the portfolio, and faculty
      promotion results were tracked for the first 2 years of portfolio use at the
      Medical College of Wisconsin. RESULTS: The ability to judge candidates'
      educational activities via a portfolio was rated to be excellent or very good by
      100% of respondents, as compared with using a traditional curriculum vitae alone.
      Promotion results indicate successful promotion of faculty using the Educator's
      Portfolio. CONCLUSIONS: As a method for evaluating scholarship in education, the
      Educator's Portfolio is an important addition to a candidate's promotion packet.

PMID- 7628651
TI  - Influences on teaching colposcopy and treatment modalities in family practice
      programs.
AB  - BACKGROUND: Colposcopy and related therapeutic modalities are taught in many
      family practice residency programs. The role of the following two factors in a
      family practice residency program's decision to teach these procedures was
      evaluated: 1) the coexistence of an obstetrics and gynecology (OB-GYN) residency
      program at the affiliated hospital and 2) the perceived attitude of community
      obstetrician-gynecologists toward family physicians performing the procedures.
      METHODS: In 1993, all 399 accredited family practice residency programs were
      surveyed, with a response rate of 86.5%. RESULTS: Ninety-three percent of
      responding programs taught colposcopy. All programs that rated community
      obstetrician-gynecologists' attitudes as positive taught colposcopy, and 91%
      taught cryotherapy. In programs rating local obstetrician-gynecologists'
      attitudes as negative, 85.5% taught colposcopy, and 71% taught cryotherapy. A co
      located OB-GYN program did not influence a family practice program's likelihood
      of teaching colposcopy or treatment modalities. CONCLUSION: A perception that
      community obstetrician-gynecologists have negative attitudes about family
      physicians performing colposcopy may dissuade some family practice programs from
      teaching colposcopy and related treatment modalities. This influence was not seen
      in programs with a co-located OB-GYN residency.

PMID- 7628653
TI  - Abdominal pain in an HMO.
AB  - BACKGROUND: Previous surveys have found that 14%-25% of the population report
      abdominal pain. Only one study examined the age-gender specific prevalence of
      abdominal pain in the population, and no study has examined the self-reported
      causes of abdominal pain. METHODS: To describe the epidemiology of abdominal pain
      in a large health maintenance organization population, 6,199 randomly selected
      members were contacted and interviewed by telephone about the occurrence of
      abdominal pain and related health care in the past year. RESULTS: Of those
      interviewed, 27% reported abdominal pain in the past year, while 38% of those
      individuals saw a physician for their pain. Women were more likely than men to
      have had pain and to have seen a physician for their pain. Fewer older
      individuals reported abdominal pain, but when pain occurred, they sought medical
      care more often than younger individuals. CONCLUSIONS: Women and younger
      individuals report abdominal pain more frequently. Women and older individuals
      are more likely to seek care for their pain.

PMID- 7628652
TI  - Clinical reasoning about new symptoms despite preexisting disease: sources of
      error and order effects.
AB  - BACKGROUND: Previous work that studied the evaluation of new, atypical symptoms
      in patients with preexisting diseases indicated that physicians largely ignored
      the past medical history and therefore erred in their diagnoses, when compared to
      a Bayesian analysis. Other studies have shown that the order in which information
      is presented to a decision maker can affect the inferences drawn, again contrary
      to a Bayesian standard. OBJECTIVES: The aim of the study was to investigate the
      source of disparity between clinical judgment and Bayesian analysis and to
      investigate the effect of alternative orders of presenting information on
      diagnostic conclusions. METHODS: Two groups of family physicians received a
      written clinical scenario. One group was given the past medical history before
      the history of present illness, the physical exam, and the laboratory data. The
      second group learned about the past medical history after all other clinical
      information had been presented. Judgments of test accuracy and probably diagnosis
      were collected at several points to identify the source of any diagnostic error.
      RESULTS: For both groups, the major source of error was in estimating the prior
      probability of disease, not in estimating the accuracy of a diagnostic test or
      updating opinions following receipt of test results. Although both groups of
      physicians received the same information, they came to markedly different
      conclusions about the most likely diagnosis. The group given the past medical
      history at the beginning of the scenario considered this information much less
      significant than did the group who received it at the end. CONCLUSIONS: Family
      physicians deviate from a Bayesian standard of reasoning by wrongly specifying
      prior probabilities and by being influenced by the order in which clinical
      information is presented.

PMID- 7628654
TI  - The pursuit of clinical effectiveness.

PMID- 7628655
TI  - Health care reform at the micro level and doing the right thing.

PMID- 7628656
TI  - [Muscle blood flow in healthy people residing in regions with extreme continental
      climate].

PMID- 7628657
TI  - [Hormonal interactions in patients with borderline arterial hypertension with and
      without vegetovascular dystonia syndrome].

PMID- 7628658
TI  - [Physiologic status of people working under conditions of exposure to low doses
      of toxic substances].

PMID- 7628659
TI  - [Regulation of oxygen metabolism in human blood leukocytes by C-reactive
      protein].

PMID- 7628660
TI  - [The spectrum of medico-biological affects of low molecular weight RNA].

PMID- 7628661
TI  - [Two types of heat accumulation in the human body under ergothermic stress].

PMID- 7628662
TI  - [Sex-related characteristics of the psychophysiologic manifestations of the
      stress-reaction in young people].

PMID- 7628663
TI  - [Periodic motor activity of the human stomach and small intestine].

PMID- 7628664
TI  - [Interrelationships between human brain activity and immune system].

PMID- 7628666
TI  - [Changes in psychophysiologic parameters as a result of teaching voluntary
      relaxation during practical lessons with students].

PMID- 7628665
TI  - [A method of computer analysis of cardiac rhythm in children based on 24-hour
      monitoring].

PMID- 7628667
TI  - [Interrelationship between the durations of adjacent respiratory cycles].

PMID- 7628668
TI  - [Psychophysiologic features of human adaptation to conditions of of mountainous
      desert climate and feasibility of its pharmacologic optimization].

PMID- 7628669
TI  - [Features of radiation hazard perception by children of various ages].

PMID- 7628670
TI  - [Psychophysiological evaluation of acute physical fatigue].

PMID- 7628671
TI  - [Psychophysiological rating as an index of the effectiveness of mental activity].

PMID- 7628672
TI  - [Functional organization of mental activity in people of varying age].

PMID- 7628673
TI  - [Individual features of resistance to emotional stress during computer work in
      students aged 15-16].

PMID- 7628674
TI  - [Correlation between EEG spectral density characteristics and parameters of
      catecholamine and serotonin metabolism].

PMID- 7628675
TI  - [Dynamics of postural change and individual features of cardiac rhythm in
      children of varying age].

PMID- 7628676
TI  - [Lung ventilation during respiration of low-temperature air].

PMID- 7628677
TI  - [Linear relaxation of human muscle after denticulate tetany of varying duration].

PMID- 7628678
TI  - [Hemodynamic response to isometric exercise in healthy people with varying types
      of blood circulation].

PMID- 7628679
TI  - [Parameters of the functional state of the body in highly qualified judo fighters
      in the final stages of training for competitions].

PMID- 7628680
TI  - [Relationship between electrokinetic properties of cell nuclei in people with
      various physiologic parameters].

PMID- 7628681
TI  - [Types of regulation of the functional state of the hemostatic system].

PMID- 7628682
TI  - In vitro hormonal regulation of glycogen phosphorylase activity in fat body of
      the tropical cockroach, Blaberus discoidalis.
AB  - Blaberus hypertrehalosemic hormone (Bld-HTH)-dependent glycogen phosphorylase
      activation was investigated using in vitro fat bodies from the cockroach,
      Blaberus discoidalis. Resting levels of active phosphorylase were decreased by
      the presence of trehalose and glucose. Phosphorylase activation was dose
      responsive to Bld-HTH and increased ca. 3-fold over a range of 0.02 to 2 nM Bld
      HTH. Maximum phosphorylase activation required only 5-min exposure to Bld-HTH;
      reversion to the inactive state began within 15 min after Bld-HTH removal and was
      completed by 60 min. Octopamine also activated phosphorylase but required 10(3)
      fold higher concentrations than did Bld-HTH. Concentrations of Bld-HTH and
      octopamine that increased active phosphorylase did not elevate fat body cAMP
      levels, although a high concentration of octopamine increased tissue cAMP levels.
      cAMP did not increase phosphorylase activity, but Ca2+ was important for both Bld
      HTH- and octopamine-dependent phosphorylase activation.

PMID- 7628683
TI  - Complete amino acid sequence of crocodile growth hormone.
AB  - This paper describes the isolation and complete amino acid sequence of growth
      hormone (GH) from the pituitary gland of the crocodile, Crocodylus novaeguineae.
      GH was detected in an alkaline extract of the pituitary by specific immunoblot
      reactivity with rabbit antisera against cattle and salmon GH and isolated in pure
      form by DEAE-cellulose chromatography and by reversed-phase high-performance
      liquid chromatography. The yield of the GH was 2.2 mg from 3.5 g of wet tissue.
      Crocodile GH consists of 190 residues and is highly similar to chicken, duck, and
      sea turtle GHs with 90-92% structural similarity, although it shows only 27%
      identity with crocodile prolactin. A molecular phylogenetic tree of GH from 39
      vertebrate species is proposed on the basis of sequence comparison.

PMID- 7628684
TI  - Isolation and characterization of a cDNA encoding for preprosomatostatin
      containing [Tyr7, Gly10]-somatostatin-14 from the endocrine pancreas of rainbow
      trout, Oncorhynchus mykiss.
AB  - Somatostatins are a diverse group of peptides known to influence various aspects
      of growth and metabolism of vertebrates. In order to further our understanding of
      the physiological roles of somatostatins in fish, we initiated an analysis of
      somatostatin gene structure and expression in rainbow trout pancreas. Using rapid
      amplification of cDNA ends polymerase chain reaction, we have isolated, cloned,
      and sequenced a novel cDNA derived from pancreatic total RNA. Sequence analysis
      revealed a 624-bp cDNA containing the complete 5'-untranslated region with a
      single initiation site 107 bases from the most 5' end and a single putative
      polyadenylation site 13 bases from the most 3' end that was terminated with a
      polyadenylated tail. The deduced protein is a 115-amino-acid preprosomatostatin
      molecule with [Tyr7,Gly10]-somatostatin-14 at the C-terminus of the coding
      region, making the rainbow trout precursor a member of the preprosomatostatin II
      family. Based on the location of putative cleavage sites, we propose that rainbow
      trout pancreatic preprosomastatin II is processed to yield a 28-amino-acid
      and/or, possibly, a 14-amino-acid somatostatin II molecule. The results also
      suggest that there has been limited conservation of the preprosomatostatin II
      gene family among teleosts.

PMID- 7628685
TI  - Differential changes in the milk concentrations of epidermal growth factor and
      insulin-like growth factor-I during lactation in the tammar wallaby, Macropus
      eugenii.
AB  - Insulin-like growth factor-I (IGF-I) and epidermal growth factor (EGF) have been
      measured in milk during lactation of the tammar wallaby (Macropus eugenii) and
      related to the total growth-promoting activity of the milk as determined in
      cultured L6 rat myoblasts. EGF increased throughout lactation from 10 ng/ml at 99
      days to 25 ng/ml at 263 days. As a greater increase occurred with total soluble
      proteins in the milk, the EGF content per milligram of protein was decreased
      slightly during lactation. That EGF is secreted in tammar milk at a relatively
      constant amount is consistent with data from eutherian mammals, even though
      actual EGF concentrations either decrease or increase during lactation in those
      species. A very different pattern of secretion was observed with IGF-I, which
      increased sixfold to a maximum of 1043 ng/ml at 205 days of lactation before
      falling to approximately 300 ng/ml toward the end of lactation. The protein
      synthesis-stimulating activity of the milk measured in myoblasts demonstrated a
      similar pattern to that obtained with IGF-I. The IGF-I changes are unlike the
      data reported in eutherian mammals in which this growth factor falls to low
      levels from high concentrations in initial colostrum. The highest concentration
      of IGF-I in tammar milk coincides with the changeover to a high fat, high
      protein, low hexose milk composition that is produced at an increased rate when
      the young leaves the pouch. IGF-I in tammar milk may be important for mammary
      gland maturation at this stage.

PMID- 7628686
TI  - Stimulation of rainbow trout gallbladder contraction by cionin, an ancestral
      member of the CCK/gastrin family.
AB  - Cionin--from the protochordate Ciona intestinalis--is a putative ancestor of
      cholecystokinin (CCK) and gastrin. Being sulfated on tyrosine in positions 7 and
      6 (from the C-terminus), characteristic for CCK and gastrin, respectively, cionin
      is a structural hybrid of the two peptides. The effects of cionin have previously
      been characterized in mammalian systems. This study examined a phylogenetically
      ancient CCK receptor, the rainbow trout (Oncorhynchus mykiss) gallbladder
      receptor, utilizing cionin, sulfated and nonsulfated CCK and gastrin, and the
      receptor antagonists L-364,718 and L-365,260. The sulfated peptides induced
      concentration-dependent contractions of isolated strips of gallbladder with equal
      efficacy and similar potencies [ED50: 42 (cionin), 23 (CCK-8-s), and 74 nM
      (gastrin-17-s)], significantly different from the nonsulfated forms [ED50: 1.7
      (CCK-8-ns) and 1.9 microM (gastrin-17-ns)]. Ten micromolar L-364,718 and L
      365,260 both weakly but significantly inhibited cionin-CCK-8-s, and gastrin-17-s
      induced contractions. L-365,260 shifted the concentration response curves 1 1/2
      decades to the right and L-364,718 only 1/2 decade. The results confirm that the
      rainbow trout gallbladder CCK receptor does not distinguish sulfated CCK from
      sulfated gastrin as do modern CCKA receptors, but does distinguish sulfated from
      nonsulfated forms of both. However, for optimal effect the receptor does not
      require a double-sulfated peptide like cionin as might be expected from the lack
      of selectively between CCK and gastrin. Finally, studies with antagonists known
      to be specific for either CCK or gastrin receptors in mammalian systems indicate
      that this ancient receptor behaves more like a mammalian CCKB receptor than as a
      CCKA receptor.

PMID- 7628687
TI  - Corticotrope and melanotrope POMC-derived peptides in relation to interrenal
      function during stress in rainbow trout (Oncorhynchus mykiss).
AB  - Plasma levels of ACTH, alpha-MSH, and N-ac-beta-END, and in vitro interrenal ACTH
      sensitivity were investigated in rainbow trout (Oncorhynchus mykiss) stressed by
      confinement and in unstressed fish treated with exogenous cortisol. Within 3 hr
      after the onset of confinement, plasma cortisol and ACTH levels were
      significantly elevated above control values, while plasma alpha-MSH, but not N-ac
      beta-END, levels were significantly decreased compared with those of unstressed
      fish. At 3 hr, sensitivity of the interrenal tissue to ACTH stimulation in vitro
      was reduced in stressed fish compared to that of unstressed controls. This
      hyposensitivity cannot be due to the intervention of alpha-MSH or N-ac-beta-END,
      because after 48 hr of confinement levels of both POMC-derived peptides were
      significantly lower than in controls, whereas interrenal tissue of stressed fish
      still responded significantly less to an ACTH challenge than tissue from control
      fish. Plasma cortisol and ACTH levels in confined fish at this time point were
      similar to those at 3 hr. Within 96 hr of the onset of confinement, plasma ACTH
      levels in stressed fish had returned to baseline levels. Plasma cortisol levels
      in stressed fish at 96 hr had also declined significantly, but were still higher
      than those in controls. The circulating cortisol level cannot be the regulatory
      factor responsible for the ACTH hyposensitivity observed after 3 and 48 hr of
      stress, because treatment of unstressed fish with exogenous cortisol (which
      resulted in elevated plasma cortisol and lower plasma ACTH and alpha-MSH levels
      compared to those of controls) did not induce a reduction in interrenal
      sensitivity to ACTH. It is suggested, instead, that these data support the
      contention that not only the initiation of the interrenal stress response, but
      also the habituation of the response, are regulated at the level of the
      hypothalamus via circulating ACTH levels.

PMID- 7628688
TI  - Angiotensin I- and II- and norepinephrine-mediated pressor responses in an
      ancient holostean fish, the bowfin (Amia calva).
AB  - Dorsal aortic blood pressure (PSYS, systolic; PDIAS, diastolic; and PDA, mean)
      and heart rate (HR) were measured in resting freshwater bowfins (n = 6), Amia
      calva L., before and after i.v. injections of 50, 100, 200, 500, and 1000 ng.kg-1
      of synthetic [Asn1, Val5]-angiotensin II (ANG II). Baseline PSYS, PDIAS, and PDA
      were 27.7 +/- 2.8, 22.4 +/- 1.8, and 24.5 +/- 2 mm Hg, respectively. Bowfins were
      only moderately responsive to ANG II in a stepwise manner and the increase in
      blood pressure became significant only at the two highest doses; lower doses
      tended only to increase arterial pressure. Pressor responses due to 200 and 500
      ng.kg-1 decayed over a greater time period compared with other doses. alpha
      Adrenergic blockade abolished 70% of the ANG II-mediated pressor responses. Eel,
      salmon, and goosefish angiotensin I (ANG I; 500 ng.kg-1) elicited similar
      vasopressor responses (magnitude and time course) which were eliminated by prior
      angiotensin converting enzyme inhibition (captopril; 2-10 mg.kg-1). Bullfrog ANG
      I evoked a pressor effect, only at a higher dose (5000 ng.kg-1). Consecutive
      norepinephrine (NE) injections (100, 200, 500, and 1000 ng.kg-1) increased PSYS,
      PDIAS, and PDA in a dose-dependent manner which was dependent on alpha
      adrenoceptors since phentolamine (1-3 mg.kg-1) abolished 80% of the pressor
      action of NE. PSYS was elevated by 100 ng.kg-1 of NE but PDIAS and PDA were
      significantly increased only at 200 ng.kg-1 ANG II and NE had no measurable
      chronotropic effect and resting HR (27.2 +/- 0.8 beats.min-1) was unchanged.
      Captopril and phentolamine treatments produced rapid hypotension and bradycardia
      (25-30%) which lasted from 15 to 30 and 20 to 40 min, respectively. The rising
      and decreasing phases of the NE-mediated pressor responses had shorter durations
      than ANG II effects. Tachyphylaxis occurred with the high doses of ANG II and NE.
      The data show that in the ancient bowfin, which evidently lacks renal
      juxtaglomerular cells, the cardiovascular system can be regulated by the renin
      angiotensin system and NE.

PMID- 7628689
TI  - Circulating catecholamine and glucose concentrations in Japanese toads (Bufo
      japonicus) during the breeding season.
AB  - We investigated the relationship between catecholamine neurohormones and glucose
      during seasonal reproductive activity in Japanese toads (Bufo japonicus). Field
      studies found that plasma epinephrine concentration increased as toads migrated
      to their breeding ponds, where amplexus most frequently took place. Blood glucose
      concentration also increased as toads arrived at the ponds, even though these
      animals did not eat during the breeding season, and there was a positive
      correlation between epinephrine and glucose levels. Blood glucose concentration
      was higher in amplectic than in solitary males, whereas this relationship did not
      occur in females. For both males and females, plasma epinephrine concentration
      was elevated during amplexus. The plasma concentration of norepinephrine was
      lower than that of epinephrine and did not correlate with either the proximity of
      the animal to the breeding ponds or the blood glucose concentration. Laboratory
      experiments showed that systemic injection of [Trp7,Leu8]gonadotropin-releasing
      hormone (sGnRH) increased plasma epinephrine to levels characteristic of
      amplectic feral toads. These results suggest that a physiological role of GnRH
      like peptides may be to stimulate epinephrine secretion and consequently to
      increase glucose production in toads under the starvation conditions associated
      with the breeding migration.

PMID- 7628690
TI  - Sexual maturity modifies the responsiveness of the pituitary-interrenal axis to
      stress in male rainbow trout.
AB  - A significant reduction in stress-induced plasma cortisol levels is apparent in
      mature male rainbow trout compared to immature fish of both sexes and of the same
      age and strain. Mean plasma cortisol levels in groups of immature fish subjected
      to a standard 1-hr confinement stress were consistently higher (range 93.9 +/-
      4.9-114.8 +/- 4.1 ng ml-1) than mean levels in mature males exposed to the same
      procedure (range 47.0 +/- 4.3-71.7 +/- 5.7 ng ml-1), throughout the 4-month
      period around spawning (P < 0.001). Body weight was not found to be a significant
      determinant of poststress cortisol level. The dissimilarity in plasma cortisol
      levels between mature and immature fish following confinement does not stem from
      differences in the dynamics of the response; during a 24-hr period of confinement
      the rate of elevation of plasma cortisol levels was similar for both mature male
      and immature fish, but mature male fish attained a significantly lower peak
      cortisol level (51.6 +/- 5.2 ng ml-1) than immature fish (89.5 +/- 7.7 ng ml-1),
      a disparity which was maintained throughout the period of stress (P < 0.05-P <
      0.001). The reduced responsiveness of the interrenal tissue of mature male fish
      during stress appears to be modulated by the hypothalamus/pituitary. Plasma ACTH
      levels in mature male trout (44 +/- 9 pg ml-1) are significantly lower than those
      in immature fish (71 +/- 9 pg ml-1, P < 0.01) within 30 min of the onset of
      confinement and remain so during a 3-hr period of confinement. These data suggest
      that the cortisol/ACTH feedback equilibrium has been modified in mature fish to a
      lower "set point." Furthermore, although stress caused a significant decline of
      plasma alpha-MSH levels in both immature fish and mature males, N-acetyl-beta
      endorphin levels were reduced only in mature male fish during confinement stress.

PMID- 7628691
TI  - Pineal and thyroid functions in newborn seals.
AB  - Daily variations of pineal and plasma melatonin and plasma thyroid hormones were
      measured in harp seals (Phoca groenlandica), grey seals (Halichoerus grypus), and
      hooded seals (Cystophora cristata), ranging in age from newborn to 14 days. In
      newborn harp seals the mean mass of the pineal gland was 273 mg (+/- 45 SEM, n =
      11), containing 49 ng (median) melatonin. In newborn, 4- and 10-day-old grey
      seals, the pineal mass was similar, weighing on average 337 mg (+/- 74, n = 6)
      and containing 90 ng melatonin. Two newborn hooded seal pups had pineals weighing
      520 and 1289 mg, with 254 and 7600 ng melatonin, respectively. There were no day
      night differences in the pineal contents of melatonin or in the number of pineal
      beta-adrenergic receptors measured in newborn harp seals, and, in newborn, 4- and
      10-day-old grey seals, there were no day-night or age differences in pineal
      melatonin content. Plasma melatonin levels were 10 times higher in newborn seals
      than in two 10-day-old grey seals and one 14-day-old harp seal pup. In all seal
      pups, the levels exhibited a 24-hr rhythmicity, with increasing night- and
      decreasing daytime concentrations. Plasma levels of thyroxine (T4) and
      triiodothyronine (T3) were generally higher in newborn seals than in 10- and 14
      day-old seals or in adult females. There was no apparent 24-hr rhythmicity, but
      the thyroid hormone levels generally declined throughout each sampling sequence.
      High pineal and thyroid activities may play a thermoregulatory role in newborn
      seals, but the results do not indicate a stimulatory action of melatonin in the
      peripheral conversion of T4 to T3. It is speculated that the large and active
      pineal gland, particularly in newborn seals, may be related to aspects of their
      diving habit.

PMID- 7628692
TI  - The protein kinase C-activated MAP kinase pathway of Saccharomyces cerevisiae
      mediates a novel aspect of the heat shock response.
AB  - The PKC1 gene of budding yeast encodes a homolog of the alpha, beta, and gamma
      isoforms of mammalian PKC that is proposed to regulate a MAPK-activation pathway.
      Mutants in this pathway undergo cell lysis resulting from a deficiency in cell
      wall construction when they attempt to grow at elevated temperatures. We show
      that the PKC1-regulated pathway is important for induced thermotolerance and that
      the MPK1 protein kinase (the MAPK of this pathway) is strongly activated by mild
      heat shock. This activation is sustained during growth at high temperature and is
      dependent on the function of pathway components proposed to function upstream of
      MPK1, including PKC1. Expression of genes under the control of known heat shock
      inducible promoter elements (HSEs and STREs) was not compromised in PKC1 pathway
      mutants, indicating that this pathway mediates a novel aspect of the yeast heat
      shock response. We propose that the heat-induced signal for pathway activation is
      generated in response to weakness in the cell wall created during growth under
      thermal stress, perhaps as a result of increased membrane fluidity. Evidence is
      presented that the mechanism by which the cell detects this weakness is by
      measuring stretch of the plasma membrane.

PMID- 7628693
TI  - p93dis1, which is required for sister chromatid separation, is a novel
      microtubule and spindle pole body-associating protein phosphorylated at the Cdc2
      target sites.
AB  - Fission yeast cold-sensitive (cs) dis1 mutants are defective in sister chromatid
      separation. The dis1+ gene was isolated by chromosome walking. The null mutant
      showed the same phenotype as that of cs mutants. The dis1+ gene product was
      identified as a novel 93-kD protein, and its localization was determined by use
      of anti-dis1 antibodies and green fluorescent protein (GFP) tagged to the
      carboxyl end of p93dis1. The tagged p93dis1 in living cells localizes along
      cytoplasmic microtubule arrays in interphase and the elongating anaphase spindle
      in mitosis, but association with the short metaphase spindle microtubules is
      strikingly reduced. In the spindle, the tagged p93dis1 is enriched at the spindle
      pole bodies (SPBs). Time-lapse video images of single cells support the
      localization shift of p93dis1 to the SPBs in metaphase and spindle microtubules
      in anaphase. The carboxy-terminal fragment, which is essential for Dis1 function,
      accumulates around the mitotic SPB. We propose that these localization shifts of
      p93dis1 in mitosis facilitates sister chromatid separation by affecting SPB and
      anaphase spindle function.

PMID- 7628694
TI  - Signal-induced site-specific phosphorylation targets I kappa B alpha to the
      ubiquitin-proteasome pathway.
AB  - The transcription factor NF-kappa B is sequestered in the cytoplasm by the
      inhibitor protein I kappa B alpha. Extracellular inducers of NF-kappa B activate
      signal transduction pathways that result in the phosphorylation and subsequent
      degradation of I kappa B alpha. At present, the link between phosphorylation of I
      kappa B alpha and its degradation is not understood. In this report we provide
      evidence that phosphorylation of serine residues 32 and 36 of I kappa B alpha
      targets the protein to the ubiquitin-proteasome pathway. I kappa B alpha is
      ubiquitinated in vivo and in vitro following phosphorylation, and mutations that
      abolish phosphorylation and degradation of I kappa B alpha in vivo prevent
      ubiquitination in vitro. Ubiquitinated I kappa B alpha remains associated with NF
      kappa B, and the bound I kappa B alpha is degraded by the 26S proteasome. Thus,
      ubiquitination provides a mechanistic link between phosphorylation and
      degradation of I kappa B alpha.

PMID- 7628695
TI  - Targeted disruption of the glucocorticoid receptor gene blocks adrenergic
      chromaffin cell development and severely retards lung maturation.
AB  - The role of the glucocorticoid receptor (GR) in glucocorticoid physiology and
      during development was investigated by generation of GR-deficient mice by gene
      targeting. GR -/- mice die within a few hours after birth because of respiratory
      failure. The lungs at birth are severely atelectatic, and development is impaired
      from day 15.5 p.c. Newborn livers have a reduced capacity to activate genes for
      key gluconeogenic enzymes. Feedback regulation via the hypothalamic-pituitary
      adrenal axis is severely impaired resulting in elevated levels of plasma
      adrenocorticotrophic hormone (15-fold) and plasma corticosterone (2.5-fold).
      Accordingly, adrenal glands are enlarged because of hypertrophy of the cortex,
      resulting in increased expression of key cortical steroid biosynthetic enzymes,
      such as side-chain cleavage enzyme, steroid 11 beta-hydroxylase, and aldosterone
      synthase. Adrenal glands lack a central medulla and synthesize no adrenaline.
      They contain no adrenergic chromaffin cells and only scattered noradrenergic
      chromaffin cells even when analyzed from the earliest stages of medulla
      development. These results suggest that the adrenal medulla may be formed from
      two different cell populations: adrenergic-specific cells that require
      glucocorticoids for proliferation and/or survival, and a smaller noradrenergic
      population that differentiates normally in the absence of glucocorticoid
      signaling.

PMID- 7628696
TI  - Activation of the Aspergillus PacC transcription factor in response to alkaline
      ambient pH requires proteolysis of the carboxy-terminal moiety.
AB  - Extremes of pH are an occupational hazard for many microorganisms. In addition to
      efficient pH homeostasis, survival effectively requires a regulatory system
      tailoring the syntheses of molecules functioning beyond the cell boundaries
      (permeases, secreted enzymes, and exported metabolites) to the pH of the growth
      environment. Our previous work established that the zinc finger PacC
      transcription factor mediates such pH regulation in the fungus Aspergillus
      nidulans in response to a signal provided by the products of the six pal genes at
      alkaline ambient pH. In the presence of this signal, PacC becomes functional,
      activating transcription of genes expressed at alkaline pH and preventing
      transcription of genes expressed at acidic pH. Here we detect two forms of PacC
      in extracts, both forming specific retardation complexes with a PacC-binding
      site. Under acidic growth conditions or in acidity-mimicking pal mutants
      (defective in ambient pH signal transduction), the full-length form of PacC
      predominates. Under alkaline growth conditions or in alkalinity-mimicking pacCc
      mutants (independent of the ambient pH signal), a proteolysed version containing
      the amino-terminal approximately 40% of the protein predominates. This
      specifically cleaved shorter version is clearly functional, both as an activator
      for alkaline-expressed genes and as a repressor for acid-expressed genes, but the
      full-length form of PacC must be inactive. Thus, PacC proteolysis is an essential
      and pH-sensitive step in the regulation of gene expression by ambient pH. Carboxy
      terminal truncations, resulting in a gain-of-function (pacCc) phenotype, bypass
      the requirement for the pal signal transduction pathway for conversion of the
      full-length to the proteolyzed functional form.

PMID- 7628697
TI  - Ectopic production of guanosine penta- and tetraphosphate can initiate early
      developmental gene expression in Myxococcus xanthus.
AB  - Amino acid or carbon limitation is sufficient to initiate fruiting body
      development in Myxococcus xanthus. In both Escherichia coli and M. xanthus the
      levels of guanosine 3'-di-5'-(tri)di-phosphate nucleotides [(p)ppGpp] rise
      transiently when cells are starved for amino acids or carbon. Ectopic increase in
      the intracellular concentration of (p)ppGpp was achieved in M. xanthus by
      introducing a copy of the E. coli relA gene, whose product catalyzes
      pyrophosphate transfer from ATP- to GTP-forming pppGpp. The E. coli RelA protein
      was detected in these M. xanthus strains, and a rise in (p)ppGpp was observed
      chromatographically. This increase in the intracellular (p)ppGpp levels was
      sufficient to activate developmentally specific gene expression. Although
      (p)ppGpp is made from GTP, the intracellular GTP pool from these strains was not
      significantly decreased. Moreover, when the GTP pool was lowered by either of two
      specific inhibitors of GTP synthesis, mycophenolic acid or decoyinine,
      development was not induced. These results suggest that M. xanthus cells can
      assess their nutritional status by monitoring the internal availability of amino
      acids through (p)ppGpp levels.

PMID- 7628698
TI  - A duplicated zone of polarizing activity in polydactylous mouse mutants.
AB  - The positional signaling along the anteroposterior axis of the developing
      vertebrate limb is provided by the zone of polarizing activity (ZPA) located at
      the posterior margin. Recently, it was established that the Sonic hedgehog (Shh)
      mediates ZPA activity. Here we report that a new mouse mutant, Recombination
      induced mutant 4 (Rim4), and two old mutants, Hemimelic extra toes (Hx) and Extra
      toes (Xt), exhibit mirror-image duplications of the skeletal pattern of the
      digits. In situ hybridization of the embryos of these mutants revealed ectopic
      expression of Shh and fibroblast growth factor-4 (Fgf-4) genes at the anterior
      margin of limb buds. The new mutation, Rim4, was mapped to chromosome 6 with
      linkage to HoxAbut segregated from HoxA. No linkage to other known polydactylous
      mutations was detected. In this mutant, ectopic expression of the Hoxd-11 gene,
      thought to be downstream of ZPA, was also observed at the anterior margin of the
      limb buds. All results indicate the presence of an additional ZPA at the anterior
      margin of limb buds in these mutants. Thus, it appears that multiple endogenous
      genes regulate the spatial localization of the ZPA in the developing mouse limb
      bud.

PMID- 7628699
TI  - Myogenic and morphogenetic defects in the heart tubes of murine embryos lacking
      the homeo box gene Nkx2-5.
AB  - The murine homeo box gene Nkx2-5 is expressed in precardiac mesoderm and in the
      myocardium of embryonic and fetal hearts. Targeted interruption of Nkx2-5
      resulted in abnormal heart morphogenesis, growth retardation and embryonic
      lethality at approximately 9-10 days postcoitum (p.c.). Heart tube formation
      occurred normally in mutant embryos, but looping morphogenesis, a critical
      determinant of heart form, was not initiated at the linear heart tube stage (8.25
      8.5 days p.c.). Commitment to the cardiac muscle lineage, expression of most
      myofilament genes and myofibrillogenesis were not compromised. However, the
      myosin light-chain 2V gene (MLC2V) was not expressed in mutant hearts nor in
      mutant ES cell-derived cardiocytes. MLC2V expression normally occurs only in
      ventricular cells and is the earliest known molecular marker of ventricular
      differentiation. The regional expression in mutant hearts of two other
      ventricular markers, myosin heavy-chain beta and cyclin D2, indicated that not
      all ventricle-specific gene expression is dependent on Nkx2-5. The data
      demonstrate that Nkx2-5 is essential for normal heart morphogenesis, myogenesis,
      and function. Furthermore, this gene is a component of a genetic pathway required
      for myogenic specialization of the ventricles.

PMID- 7628700
TI  - Compound mutants for the paralogous hoxa-4, hoxb-4, and hoxd-4 genes show more
      complete homeotic transformations and a dose-dependent increase in the number of
      vertebrae transformed.
AB  - The Hox gene products are transcription factors involved in specifying regional
      identity along the anteroposterior body axis. In the mouse, several single
      mutants for Hox genes show variably penetrant, partial homeotic transformations
      of vertebrae at their anterior limits of expression, suggesting that compound Hox
      mutants might show more complete transformations with greater penetrance than the
      single Hox mutants. Compound mutants for the paralogous group 3 genes, hoxa-3 and
      hoxd-3, show deletion of a cervical vertebrae, which is not readily interpretable
      in terms of an alteration in regional identity. Here, we report the skeletal
      phenotypes of compound mutants in the group 4 Hox genes, hoxa-4, hoxb-4, and hoxd
      4. Mice mutant for each of these genes were intercrossed to generate the three
      possible double mutant combinations and the triple mutant. In contrast to the
      hoxa-3, hoxd-3 double mutants, group 4 Hox compound mutants displayed clear
      alterations in regional identity, including a nearly complete transformation of
      the second cervical vertebrae toward the morphology of the first cervical
      vertebra in one double mutant combination. In comparing the types of homeotic
      transformations observed, different double mutant combinations showed different
      degrees of synergism. These results suggest a certain degree of functional
      redundancy among paralogous genes in specifying regional identity. Furthermore,
      there was a remarkable dose-dependent increase in the number of vertebrae
      transformed to a first cervical vertebra identity, including the second through
      the fifth cervical vertebrae in the triple mutant. Thus, these genes are required
      in a larger anteroposterior domain than is revealed by the single mutant
      phenotypes alone, such that multiple mutations in these genes result in
      transformations of vertebrae that are not at their anterior limit of expression.

PMID- 7628701
TI  - Cloning and sequencing of a gene from the archaeon Pyrococcus furiosus with high
      homology to a gene encoding phosphoenolpyruvate synthetase from Escherichia coli.
AB  - A gene from the hyperthermophilic archaeon Pyrococcus furiosus, strain Vc1 (DSM
      3638), contains an 817-amino-acid open reading frame which shows 42% identity to
      the phosphoenolpyruvate (PEP) synthetase of Escherichia coli. This putative P.
      furiosus PEP synthetase is slightly larger than the E. coli enzyme, the region
      between residues 58 and 89 being absent from the latter.

PMID- 7628702
TI  - Isolation and characterization of ten mutator alleles of the mitochondrial DNA
      polymerase-encoding MIP1 gene from Saccharomyces cerevisiae.
AB  - Ten mutator alleles of MIP1, the gene encoding mitochondrial (mt) DNA polymerase,
      have been isolated after in vitro random mutagenesis. Five mutations causing a
      100-400-fold increase in the frequency of erythromycin-resistant (ErR) mt mutants
      in yeast mapped to the 3'-5' exonuclease (Exo) domain, and mainly to the three
      conserved motifs Exo1, Exo2 and Exo3 of this domain, highlighting the importance
      of proofreading in accurate mt DNA replication. The essential role of the
      invariant glutamate at the Exo1 site was confirmed and the participation of four
      amino acids (aa) in the 3'-5' Exo function revealed. Another mutation that is
      located between the Exo1 and Exo2 sites produced an extremely strong mutator
      phenotype associated with impaired DNA replication, but could be assigned neither
      to a conserved aa nor to a conserved portion of the 3'-5' exonuclease domain. The
      importance of the polymerization domain in accurate mt DNA replication was
      pointed out by three mutator mutations. Two of these severely impaired mt DNA
      replication and were assigned to a subdomain of the polymerase which probably
      corresponds to the 'fingers' module of the Klenow (large) fragment of Escherichia
      coli DNA polymerase I (PolIk). The third, which did not alter the efficiency of
      DNA replication, was located at the active center of the polymerization reaction.
      Finally, the mutation, R1001I, mapped to the C-terminal part of the MIP1 protein
      which has no counterpart in prokaryotic DNA polymerases.

PMID- 7628703
TI  - Sequence similarities between the yeast chromosome segregation protein Mif2 and
      the mammalian centromere protein CENP-C.
AB  - A short stretch of strong homology between the Saccharomyces cerevisiae
      chromosome segregation protein Mif2 and the DNA-binding motifs of the Drosophila
      D1 and mammalian HMGI(Y) chromosomal proteins suggested that Mif2 may act
      directly on chromosomes. Because this conserved motif is involved in binding A.T
      DNA, it was proposed that Mif2 may interact with chromosomes at the highly A + T
      rich DNA element found in yeast centromeres. Comparison of the Mif2 amino-acid
      sequence with sequence databases showed that Mif2 shares at least two regions of
      similarity with the mammalian centromere protein CENP-C, suggesting an
      evolutionary conservation of centromere protein function from yeast to mammals.
      The order, spacing and location of these regions are also similar in the two
      proteins. Sequence analysis of several conditional lethal alleles of MIF2
      generated by random mutagenesis revealed mutations in regions homologous to CENP
      C, as well as in the highly conserved A.T DNA-binding motif. A potential
      phosphorylation site for p34cdc2 kinase located adjacent to the A.T DNA-binding
      motif was also found to be mutated in one of the mutants, suggesting that
      phosphorylation at this site may be important for Mif2 function and possibly for
      DNA binding.

PMID- 7628704
TI  - STT10, a novel class-D VPS yeast gene required for osmotic integrity related to
      the PKC1/STT1 protein kinase pathway.
AB  - We report the genetic and biochemical properties of a staurosporine (ST)- and
      temperature-sensitive mutant, stt10, of Saccharomyces cerevisiae. The stt10
      mutant shows an osmoremedial phenotype in a medium with 1 M sorbitol. ST
      sensitivity of the stt10 mutant was suppressed by overexpression of PKC1/STT1,
      showing the genetic interactions of STT10 with the PKC1/STT1 pathway. The
      nucleotide sequence of STT10 predicts a hydrophilic protein composed of 577 amino
      acids that possesses 20-25% sequence similarity with yeast Slp1/Vam5p, Sec1p and
      Sly1p, and nematode Unc-18. The stt10 deletion mutant is viable and shows a
      typical class-D vacuolar protein sorting defective (vps) phenotype. Vacuoles from
      stt10 cells have a normal vacuolar H(+)-ATPase activity, but are defective in
      vacuolar acidification. Genetic studies of yeast mutants carrying delta stt10,
      delta bck1, stt1/pkc1 or stt4 have revealed that their functions are
      phenotypically related to maintenance of cellular osmotic integrity.

PMID- 7628705
TI  - A single tyrosine differentiates active and inactive Trypanosoma cruzi trans
      sialidases.
AB  - Several genes encode members of the Trypanosoma cruzi (Tc) trans-sialidase (TS)
      family. These proteins contain an enzymatic domain on the N terminus, the only
      one required for TS activity, and an antigenic domain (SAPA (shed acute phase
      antigen) amino acid (aa) repeats) on the C terminus. Only some members of this
      glycoprotein family are enzymatically active. The complete sequence of two clones
      encoding the enzymatic domain of active and inactive protein from each of two Tc
      strains has now been obtained. Comparison of these sequences showed a limited
      divergence among them: 20 out of the 642 deduced aa in the enzymatic domain were
      found to differ. From these 20 aa, only one was found to be essential for
      enzymatic activity. A Tyr342 residue is deduced in both active proteins while a
      His342 is present in both inactive ones. This naturally occurring Tyr342-->His
      substitution completely abolished the TS activity. In addition to Tyr342, a
      second deduced aa, Pro231, was found to be necessary for full enzymatic TS
      activity; a Pro231-->Ala change rendered the TS protein partially active.
      Fourteen aa residues, including Tyr342, out of the 16 aa in the active site of a
      sialidase from Salmonella typhimurium are present at the same or very similar
      positions in the Tc TS.

PMID- 7628706
TI  - A single expression system for the display, purification and conjugation of
      single-chain antibodies.
AB  - To facilitate the purification and conjugation of single-chain antibodies (scFv)
      selected from a phage display library, we have incorporated His6, an amber stop
      codon and a C-terminal Cys into a surface expression vector. The vector also
      contains a lacIq gene for improving the efficiency of regulation and a sequence
      coding for a marker peptide.

PMID- 7628707
TI  - Mutations in HU and IHF affect bacteriophage T4 growth: HimD subunits of IHF
      appear to function as homodimers.
AB  - The Escherichia coli nucleoid-associated DNA-binding proteins HU and IHF are
      required for numerous biological processes, including phage growth (e.g., lambda,
      phi 80, Mu and f1) and DNA replication. Here, we show that growth of T4 phage is
      inhibited both in hupA hupB and himA himD double mutants. The growth profile of
      triple mutants (hupA hupB himA and hupA hupB himD) suggests that HimD subunits
      can form homodimers, which are functionally competent for supporting in vivo
      growth of phage T4.

PMID- 7628709
TI  - A Saccharomyces cerevisiae gene essential for viability has been conserved in
      evolution.
AB  - To identify the gene coding for the endonuclease which processes the 3' end of
      mitochondrial (mt) tRNA transcripts in Saccharomyces cerevisiae, nuclear
      mutations able to complement a mt mutant (Ts932) defective for this process were
      isolated and analyzed. One of these mutants exhibited a growth defect both on
      respiratory and fermentable media. Complementation of this phenotype with a S.
      cerevisiae centrometric wild-type genomic library has allowed us to identify a
      new essential S. cerevisiae gene strongly conserved in various eukaryotic
      organisms.

PMID- 7628708
TI  - Cloning of the pfaP gene of Leptospira borgpetersenii.
AB  - A lambda gt11 library constructed with Leptospira borgpetersenii DNA was screened
      with monoclonal antibodies (mAb) recognizing a periplasmic flagella-associated
      protein. A plaque expressing a fusion protein (lambda F15) which reacted with the
      mAb was isolated and the nucleotide sequence analyzed. The deduced amino-acid
      (aa) sequence indicates that the pfaP gene belongs to a group of bacterial genes
      whose products share aa sequence and possibly functional homologies with sppA, an
      Escherichia coli signal peptidase-encoding gene.

PMID- 7628710
TI  - Sequence and structure of Penicillium chrysogenum phoG, homologous to an acid
      phosphatase-encoding gene of Aspergillus nidulans.
AB  - A Penicillium chrysogenum (Pc) gene (phoG), homologous to an Aspergillus nidulans
      (An) gene which confers phosphate-non-repressible acid phosphatase (APase)
      activity, has been cloned and sequenced. The 2.9-kb genomic sequence corresponds
      to two ORFs of 149 and 1630 bp encoding a protein of 593 amino acids (aa). As
      verified by cDNA sequencing, the coding region is interrupted by an 85-bp intron.
      The deduced aa sequence of phoG reveals 61% aa identity to the translated long
      ORF of the An APase-encoding gene. Northern blot analysis indicated a 2.3-kb
      transcript in approximately equivalent amount in mycelia grown under different
      phosphate concentrations.

PMID- 7628711
TI  - Display of biologically active proteins on the surface of filamentous phages: a
      cDNA cloning system for the selection of functional gene products linked to the
      genetic information responsible for their production [Gene 137 (1993) 69-75].

PMID- 7628712
TI  - Integrative vectors for heterologous gene expression in Streptomyces spp.
AB  - Integrative expression vectors for heterologous expression of the genes in
      Streptomyces were developed. The vectors are comprised of a strong constitutive
      promoter, PE, a synthetic ribosome-binding site, ATG start codon, multiple
      cloning site, transcription terminator and hygromycin-resistance-encoding gene.
      The vectors also contain a ColE1 replicon for propagation in Escherichia coli and
      a wide-host-range Streptomyces integration element, the mini-circle, to direct
      the insertion of the vectors into the Streptomyces genome at the mini-circle
      attachment site. HyR transformants are stable in the absence of drug selection.
      Conjugative derivatives were also constructed by incorporating oriT, the origin
      of transfer of the IncP plasmid RK2, into these vectors, and conjugal transfer
      was demonstrated from an appropriate E. coli donor to Steptomyces lividans (Sl).
      Derivatives of these vectors potentially useful for gene disruption, as well as
      complementation, are also described. Replicative forms of the constructed mini
      circle-based vectors in Sl, that co-exist with the integrated copy of the vector,
      were also present without any apparent instability problems. The utility of the
      vectors was demonstrated by expression of the gene encoding 31-O
      methyltransferase, which is involved in methylation at position 31 of the
      immunosuppressive drug FK506, in Sl.

PMID- 7628713
TI  - In memoriam Alexander (Leszek or Leshek) Kohn (1919-1994). A personal tribute.

PMID- 7628714
TI  - The PAH2 gene is required for peroxisome assembly in the methylotrophic yeast
      Hansenula polymorpha and encodes a member of the tetratricopeptide repeat family
      of proteins.
AB  - Peroxisome assembly mutants in the methylotrophic yeast, Hansenula polymorpha,
      were selected by a novel procedure involving the inability of mutants to use both
      oleic acid and methanol as carbon sources. These compounds are both metabolized
      within peroxisomes through two different enzymatic pathways. 15 mutant strains
      called mut (methanol non-utilizing) were isolated. These strains were assigned to
      ten genetic complementation groups. Subcellular fractionation analysis showed
      that peroxisomal matrix enzymes were mislocalized to the cytoplasm in mut
      strains. Electron microscopy confirmed that the inability of mut strains to grow
      on oleic acid and methanol was due to defects in peroxisome assembly. Functional
      complementation of a mutant strain, mut2, with a plasmid library of H. polymorpha
      genomic DNA sequences has identified a gene, PAH2, that restores growth on
      methanol and the correct localization of matrix enzymes to the peroxisome. PAH2
      encodes Pah2p, a polypeptide of 569 amino acids that is a member of the
      tetratricopeptide repeat (TPR) family of proteins. Pah2p shows identity with
      Pas8p and Pas10p, two proteins required for peroxisome assembly in the yeasts
      Pichia pastoris and Saccharomyces cerevisiae, respectively, and which have been
      suggested to be receptors that recognize peroxisomal targeting signal-1 (PTS1)
      motifs.

PMID- 7628715
TI  - Volvox carteri alpha 2- and beta 2-tubulin-encoding genes: regulatory signals and
      transcription.
AB  - Microtubules (MT) carry out several specialized morphogenetic functions in the
      multicellular green alga Volvox carteri (Vc), in addition to functions also
      executed in its closest unicellular relative, Chlamydomonas reinhardtii (Cr). To
      find out if these differences in morphogenetic complexity are reflected in
      tubulin (Tub) differences, we have compared the Vc alpha tub and beta tub genes
      with their Cr counterparts. The Vc genome contains two alpha tub and two beta tub
      genes. We report here the sequences of the alpha 2tub and beta 2tub genes, and
      thus complete the set of four tub sequences. The two alpha tub and two beta tub
      genes code for identical 451 (alpha) and 443 (beta) amino acid (aa) polypeptides;
      they differ from the Cr homologs in two (alpha) and one (beta) residues,
      respectively. Silent nucleotide (nt) exchanges between sibling genes are much
      more frequent in Vc than in Cr (12 vs. 2%), probably owing to a more stringent
      codon bias in the latter alga. Transcription of alpha 2tub and beta 2tub starts
      with an A, 26 bp (alpha 2) or 25 bp (beta 2) downstream from the TATA box. A 16
      bp promoter element upstream and a G + C-rich sequence downstream from the TATA
      box are conserved in all tub of both species. Moreover, a 28-bp element of
      conserved sequence, and hence of possible functional significance, was found at
      similar locations in the 5' untranslated region (UTR) of all four alpha tub. A
      conserved TGTAA downstream from the translation stop codon represents the algal
      poly(A)-addition signal (in both Vc and Cr).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7628716
TI  - SgfI, a new type-II restriction endonuclease that recognizes the octanucleotide
      sequence 5'-GCGAT/CGC-3'.
AB  - A new restriction endonuclease (ENase), SgfI, has been isolated from the
      bacterium Streptomyces sp. SgfI recognizes the 8-bp palindrome 5'-GCGATCGC-3' and
      cleaves double-stranded DNA after the T in this sequence, producing a two-base 3'
      overhang compatible with PvuI termini. SgfI is a rare-cutting ENase and should be
      useful for megabase mapping experiments.

PMID- 7628717
TI  - Mini-Tn10 transposon derivatives for insertion mutagenesis and gene delivery into
      the chromosome of gram-negative bacteria.
AB  - Four mini-Tn10 derivatives bearing the nptII, cat, aacC1 and tet genes along with
      MCS of the pBluescriptII plasmid were constructed. These derivatives are embedded
      into the gamma-ori R6K-based suicide plasmid pBSL177, which can be mobilized into
      a broad range of hosts by the RP4 plasmid. The relatively small size and the
      presence of the mutant ATS Tn10 transposase gene, fused to Ptac promoter, as well
      as the versatile MCS of the pBluescriptII plasmid make these vectors a reliable
      tool for insertion mutagenesis and chromosomal insertion of the cloned DNA
      fragments.

PMID- 7628718
TI  - Improved antibiotic-resistance gene cassettes and omega elements for Escherichia
      coli vector construction and in vitro deletion/insertion mutagenesis.
AB  - Several antibiotic-resistance gene cassettes and omega elements for Escherichia
      coli vector construction include the aacC1, aadA+, bla, cat, nptII and tet gene
      cassettes, and also the omega-Gm, omega-Sm, omega-Ap, omega-Cm, omega-Km and
      omega-Tc elements. Both cassettes and elements are flanked by pBluescriptII
      plasmid multiple cloning sites (MCS) duplicated in inverted (symmetric MCS) or
      direct (tandem MCS) orientation. Genes that were modified in order to remove
      sites for the most common restriction endonucleases from their coding regions
      (except aacC1 and aadA+) were used for cassette and omega-element construction.

PMID- 7628720
TI  - Evidence for an evolutionary relationship among type-II restriction
      endonucleases.
AB  - Type-II restriction-modification (R-M) systems comprise two enzymes, a DNA
      methyltransferase (MTase) and a restriction endonuclease (ENase), each of which
      specifically interact with the same 4-8 bp sequence. All type-II MTases share
      several amino acid (aa) sequence motifs, which makes an evolutionary relatedness
      among these enzymes probable. The type-II ENases, in contrast, except for some
      homologous isoschizomers, do not share significant aa sequence similarity.
      Therefore, ENases in general have been considered unrelated. Here we show that in
      addition to the analysis of the genotype (aa sequence), a comparison of the
      phenotype (recognition sequence) of these enzymes can provide independent
      information regarding evolutionary relationships, and thereby, help to analyze
      the significance of weak aa sequence similarities. Multistep Monte-Carlo analyses
      were employed to demonstrate that the recognition sequences of those ENases,
      which were found to be related by a progressive multiple aa sequence alignment,
      are more similar to each other than would be expected by chance. This analysis
      supports the notion that not only type-II MTases, but also type-II ENases did not
      arise independently in evolution, but rather evolved from one or a few primordial
      DNA-modifying and DNA-cleaving enzymes, respectively.

PMID- 7628719
TI  - The partition region of plasmid QpH1 is a member of a family of two trans-acting
      factors as implied by sequence analysis.
AB  - Sequencing analysis revealed that the partition region of the Coxiella burnetii
      plasmid QpH1 contains a putative operon, designated qsopAB. The two open reading
      frames (ORFs), qsopA and qsopB, specify the QsopA and QsopB proteins, with
      deduced molecular masses of 45.7 and 37.6 kDa, respectively. Maxicell analysis
      demonstrated that although qsopB was located downstream from qsopA, it had its
      own promoter that was active in Escherichia coli. Several direct or inverted
      repeats were found around this operon. The most distinct was a 20-bp long
      imperfect palindrome in the promoter region of qsopA, with homology to a
      palindrome in the promoter region of P1 parA. Structurally qsopAB was similar to
      parAB of the P1 plasmid. However, at the amino acid (aa) sequence level, QsopA
      and QsopB were closest to the F plasmid SopA and SopB proteins, respectively.
      QsopA shared 58.0% homology and 32.7% identity with SopA, but only 45-50%
      homology and 22-26% identity with other members of the protein A partition
      family. QsoB had even lower (41-45%) homology to other members of the protein B
      partition family, with the highest homology and identity to SopB. Despite lower
      homologies, both QsopA and QsopB did share conserved aa sequence regions and
      invariant residues with other members within each family.

PMID- 7628721
TI  - A second putative mRNA binding site on the Escherichia coli ribosome.
AB  - Translation in bacteria is initiated by a base-pairing interaction between the
      extreme 3'-end of the small-subunit rRNA and a purine-rich domain (Shine-Dalgarno
      (SD) sequence) preceding the initiation codon at the 5'-end of most bacterial
      mRNAs. Here, we describe the identification of a second functional and
      alternative site on the Escherichia coli ribosome which is capable of interacting
      with mRNA devoid of SD sequences and initiate the translation. This site is
      localized between nt 1340 and 1360 of the 16S rRNA in E. coli and is
      complementary to the untranslated region at the 5'-end of tobacco mosaic virus
      RNA (omega sequence).

PMID- 7628722
TI  - Construction of Actinobacillus pleuropneumoniae-Escherichia coli shuttle vectors:
      expression of antibiotic-resistance genes.
AB  - We constructed several cloning vectors, designated pGZRS-18/19 and pGZRS-38/39,
      which were based on an endogenous Actinobacillus pleuropneumoniae (Apl) 4.3-kb
      plasmid. They carry the lacZ alpha-complementation fragment and MCS from
      pUC18/19, and either the bla gene under the control of a putative Apl promoter or
      the KmR gene from Tn903. These vectors replicate in representative strains of Apl
      serotypes 1 and 7, Escherichia coli, Pasteurella haemolytica (Ph) and Haemophilus
      (Actinobacillus) actinomycetemcomitans. We also found that Apl and Ph did not
      express genes under the control of the lacZ or bla promoters, suggesting that
      their RNA polymerases may not utilize these promoters.

PMID- 7628723
TI  - Construction of an Actinobacillus pleuropneumoniae-Escherichia coli cosmid
      cloning vector [Gene 160 (1995) 81-86].
AB  - We constructed a cosmid vector, pSW206, which should be useful for the
      construction of genomic libraries of Actinobacillus pleuropneumoniae (Apl) DNA.
      pSW206 is based on the broad-host-range plasmid RK2 and can be introduced into
      Apl by conjugation.

PMID- 7628724
TI  - Characterization and heterologous expression of the tetL gene and identification
      of iso-ISS1 elements from Enterococcus faecalis plasmid pJH1.
AB  - The tetracycline-resistance (TcR) determinant of the Enterococcus faecalis
      plasmid pJH1 has been identified and located on a 2.2-kb RsaI-EcoRI fragment. The
      fragment was cloned in Escherichia coli, and specified TcR in this host. The
      nucleotide (nt) sequence of the cloned fragment showed the presence of an open
      reading frame (ORF) of 1374 bp, designated tetL. The nt sequence of tetL from
      pJH1 was identical to that of the tetL present on pLS1 from Streptococcus
      agalactiae. Upstream of the pJH1 tetL, part of another ORF was found that, except
      for two single-nt substitutions, was identical to an iso-ISS1 element from
      Lactococcus lactis. Hybridization studies indicated the presence of several ISS1
      like elements in plasmid pJH1, but not on the En. faecalis chromosome. To study
      its usefulness as a marker in Gram+ organisms, the pJH1 tetL was cloned on the
      broad-host-range plasmid pNZ124, resulting in pNZ280, that was found to give
      resistance to 40 micrograms Tc/ml in Lc. lactis and Bacillus subtilis.

PMID- 7628725
TI  - Identification and characterization of IS1296 in Mycoplasma mycoides subsp.
      mycoides SC and presence in related mycoplasmas.
AB  - IS1296, a new insertion sequence belonging to the IS3 family of insertion
      elements has been identified in Mycoplasma mycoides subsp. mycoides (Mmm) biotype
      small colony (SC), the agent of contagious bovine pleuropneumonia (CBPP). IS1296
      is 1485-bp long and has 30-bp inverted repeats. It contains two open reading
      frames, ORFA and ORFB, which show significant similarities to the ORFs which
      encode the transposase function of IS elements of the IS3 family, in particular
      IS150 of Escherichia coli. IS1296 is present in 19 copies in Mmm SC-type strain
      PG1 and in 18 copies in a recently isolated field strain L2. It seems to
      transpose at low frequency in Mmm SC. IS1296 is also present in 5 copies in Mmm
      biotype large colony (LC)-type strain Y-goat, and in two copies in Mycoplasma sp.
      'bovine group 7' reference strain PG50. It is, however, not present in other
      species of the 'mycoides cluster' or other closely related Mycoplasma sp. of
      ruminants.

PMID- 7628726
TI  - Preferential formation of the hydroperoxide of linoleic acid in choline
      glycerophospholipids in human erythrocytes membrane during peroxidation with an
      azo initiator.
AB  - The formation of phospholipid hydroperoxides was monitored in human red blood
      cell (RBC) membranes that had been peroxidized with an azo initiator.
      Peroxidation of RBC membranes caused a profound decrease in the amount of
      polyunsaturated fatty acids and concomitantly hydroperoxides, as primary products
      of peroxidation, appeared in the phospholipids. Hydroperoxides were predominantly
      generated in choline glycerophospholipid (CGP), while the extent of formation of
      ethanolamine glycerophospholipid (EGP) hydroperoxides was low and their presence
      was transient. Hydroxy and hydroperoxy moieties in CGP were identified as 9
      hydroxy and 13-hydroxy octadecanoic acid, derived from linoleic acid, by gas
      chromatography-mass spectrometric analysis. No consistent generation of
      hydroperoxide from arachidonic acid was evident in CGP. The CGP-hydroperoxide
      accounted for approximately 76% of linoleic acid consumed during peroxidation of
      RBC membranes. The prominent generation of phospholipid hydroperoxides was
      observed in the linoleic acid-rich membranes from rabbit RBC, indicating that the
      level of linoleic acid in phospholipids determines, in part, the extent of
      formation of phospholipid hydroperoxides. Aldehydic phospholipids, as secondary
      products of peroxidation, were detected in oxidized membranes. EGP was the most
      prominent aldehydic phospholipid, while negligible amounts of aldehydic CGP were
      formed. This study indicates that the process of oxidation of individual
      phospholipids clearly differs among phospholipids and depends on the structure of
      each.

PMID- 7628727
TI  - DNA base modifications and membrane damage in cultured mammalian cells treated
      with iron ions.
AB  - We investigated DNA base damage in mammalian cells exposed to exogenous iron ions
      in culture. Murine hybridoma cells were treated with Fe(II) ions at
      concentrations of 10 microM, 100 microM, and 1 mM. Chromatin was isolated from
      treated and control cells and analyzed by gas chromatography/mass spectrometry
      for DNA base damage. Ten modified DNA bases were identified in both Fe(II)
      treated and control cells. The quantification of modified bases was achieved by
      isotope-dilution mass spectrometry. In Fe(II)-treated cells, the amounts of
      modified bases were increased significantly above the background levels found in
      control cells. Dimethyl sulfoxide at concentrations up to 1 M in the culture
      medium did not significantly inhibit the formation of modified DNA bases. A
      mathematical simulation used to evaluate the plausibility of DNA damage upon
      Fe(II) treatment predicted a dose-dependent response, which agreed with the
      experimental results. In addition, Fe(II) treatment of cells increased the cell
      membrane permeability and caused production of lipid peroxides. The nature of DNA
      base lesions suggests the involvement of the hydroxyl radical in their formation.
      The failure of dimethyl sulfoxide to inhibit their formation indicates a site
      specific mechanism for DNA damage with involvement of DNA-bound metal ions.
      Fe(II) treatment of cells may increase the intracellular iron ion concentration
      and/or cause oxidative stress releasing metal ions from their storage sites with
      subsequent binding to DNA. Identified DNA base lesions may be promutagenic and
      play a role in pathologic processes associated with iron ions.

PMID- 7628728
TI  - Determination of 8-hydroxydeoxyguanosine by an immunoaffinity chromatography
      monoclonal antibody-based ELISA.
AB  - The postulated importance of oxidative damage to DNA in aging and age-related
      degenerative pathologies such as cancer has prompted efforts to develop sensitive
      quantitation methods. 8-Hydroxy-2'-deoxyguanosine (8-OHdG) is a widely used
      marker for oxidative damage to DNA. To develop an immunoassay for quantitation of
      8-OHdG, two monoclonal antibodies have been developed and characterized by
      competitive enzyme-linked immunosorbent assay (ELISA). Antibody 1F7 has 50%
      inhibition at 5 pmol 8-OHdG and 1 x 10(5) pmol dG, while antibody 1F11 has 50%
      inhibition at 2.5 pmol 8-OHdG and 2000 pmol dG. Both antisera crossreact with
      guanosine and several structurally related derivatives, including 6- and 8
      mercaptoguanosine, 8-bromoguanosine, 8-methylguanine, and 7-methylguanosine.
      Immunoaffinity columns were prepared with antibody 1F7, which exhibits higher
      selectivity than 1F11, to isolate 8-OHdG from DNA hydrolyzates followed by ELISA
      quantitation with antibody 1F11. This method allows the analysis of approximately
      one 8-OHdG/10(5) dG using 100 micrograms DNA. To validate the assay, DNA
      extracted from human placental tissues were assayed by both ELISA and HPLC with
      electrochemical detection. Values by both methods correlated well (r = 0.87, p <
      0.001), but the levels determined by ELISA were approximately sixfold higher than
      those determined by HPLC. This may be due to oligonucleotides detected by the
      ELISA but not the HPLC method or crossreactivity with other damaged bases present
      in the immunoaffinity purified material. Placental samples from current smokers
      had significantly higher 8-OHdG by ELISA than those from nonsmokers (p < 0.05).
      The method of immunoaffinity purification combined with ELISA quantitation has
      sufficient sensitivity for detecting 8-OHdG in human DNA samples. Although
      absolute values are higher than those determined by HPLC, the method provides a
      good alternative to the HPLC-EC method for monitoring relative oxidative damage
      in molecular epidemiological studies.

PMID- 7628729
TI  - Reactions of oxyl radicals with DNA.
AB  - The importance of radical-induced damage to DNA is apparent from the ever
      increasing number of publications in this area. This review focuses on the damage
      caused to DNA by reactive oxygen-centred radicals, however formed. These may be
      hydroxyl radicals, which arise either from the radiolysis of water by ionizing
      radiation (gamma-rays or X-rays), or from a purely chemical source.
      Alternatively, metal-bound oxyl radicals (M-O.) are also active intermediates in
      DNA-cleaving reactions and may be formed from synthetic compounds or from natural
      products such as bleomycin (BLM). Chemical mechanisms leading to the observed
      degradation products are covered in detail. The biological effects of some of the
      DNA base lesions formed are touched upon, concentrating on the molecular
      mechanisms behind the initial events that lead to mutagenesis.

PMID- 7628730
TI  - Oxidative stress during exercise: implication of antioxidant nutrients.
AB  - Research evidence has accumulated in the past decade that strenuous aerobic
      exercise is associated with oxidative stress and tissue damage in the body. There
      is indication that generation of oxygen free radicals and other reactive oxygen
      species may be the underlying mechanism for exercise-induced oxidative damage,
      but a causal relationship remains to be established. Enzymatic and nonenzymatic
      antioxidants play a vital role in protecting tissues from excessive oxidative
      damage during exercise. Depletion of each of the antioxidant systems increases
      the vulnerability of various tissues and cellular components to reactive oxygen
      species. Because acute strenuous exercise and chronic exercise training increase
      the consumption of various antioxidants, it is conceivable that dietary
      supplementation of specific antioxidants would be beneficial.

PMID- 7628731
TI  - Transient reduction of autoantibodies against oxidized LDL in patients with acute
      myocardial infarction.
AB  - Fifteen consecutive patients (mean age 66 +/- 14, range 31-82) with an acute
      myocardial infarction (MI) suitable for thrombolytic therapy were included in
      this study. Autoantibodies against oxidized low-density lipoprotein (LDL) were
      determined by enzyme-linked immunosorbent assay (ELISA). Patients (n = 10) with
      marked elevation of the MB isoenzyme of creatinine kinase (CK-MB)-mass had
      significant decreases of oLDL-Ab during the acute phase, with a minimum after 8 h
      following the onset of thrombolytic therapy (within-group significance: p < .001;
      between groups: p = .01). Patients (n = 5) with CK-MB-mass values less than 70
      ng/ml did not show this phenomenon. Furthermore, significant correlations existed
      between CK-MB-mass and oLDL-Ab after 6 and 8 h (n = 15; r = .72; p = .003) and
      the time of the highest CK-MB-mass values (after 12 h) and the time of the
      maximal decrease of oLDL-Ab (after 8 h) (r = .74; p = .003). Our observations
      provide further evidence for the release of free radicals and for increased lipid
      peroxidation during reperfusion after prolonged ischemia. The decrease of oLDL-Ab
      appears to be a marker for the severity of MI.

PMID- 7628732
TI  - Antioxidant and cytotoxic tocopheryl quinones in normal and cancer cells.
AB  - We found previously that [d]-alpha-tocopherol (alpha-T) and [d]-gamma-tocopherol
      (gamma-T) are lipid antioxidants (thiobarbituric acid test) in model systems
      containing arachidonic acid (AA), cumene hydroperoxide, and Fe3+ and in smooth
      muscle cell (SMC) cultures challenged with AA. We now show that [d]-alpha
      tocopherylquinone (alpha-TQ), [d]-delta-tocopherylquinone (delta-TQ), and [d]
      gamma-tocopherylquinone (gamma-TQ) are antioxidants at low concentrations and
      prooxidants at high concentrations in the model system. Prooxidant activity is
      greater with gamma-TQ than either alpha-TQ or delta-TQ. Low concentrations of
      alpha-TQ, delta-TQ, and gamma-TQ are also antioxidants in SMC cultures challenged
      with AA. Unlike alpha-TQ, partially substituted gamma-TQ and glutathione (GSH)
      form a Michael adduct which has been purified and characterized. We found
      previously that alpha-T, gamma-T, and alpha-TQ are mitogenic in SMC. We now
      report that both delta-TQ and gamma-TQ but not alpha-TQ show concentration
      dependent cytotoxicity (changes in morphology, propidium iodide stain) in SMC
      cultures. Cytotoxicity is greater with gamma-TQ than delta-TQ. An acute
      lymphoblastic leukemia (ALL) cell line shows greater chemosensitivity (MTT and
      Neutral Red assays) to gamma-TQ than to either doxorubicin (DOX) or vinblastine
      (VLB). An ALL cell line resistant to both DOX and VLB retains the same
      chemosensitivity to gamma-TQ as the drug-sensitive ALL cell line. ALL cell lines
      are unaffected by either alpha-TQ or the GSH Michael adduct of gamma-TQ. These
      data show that partially substituted tocopheryl quinones capable of forming
      Michael adducts are potential chemotherapeutic agents for multidrug-resistant
      cancer cells.

PMID- 7628733
TI  - Lipid peroxidation contributes to age-related membrane rigidity.
AB  - The aim of this work was to assess the relative contributions of lipid
      peroxidation and cholesterol content to the increase in membrane rigidity
      observed during senescence. Membrane fluidity was manipulated through exposure to
      peroxidized or cholesterol-loaded liposomes. Small unilamella liposomes were
      prepared and either peroxidized by Fe(++)-ADP-ascorbic acid or loaded with
      cholesterol. After incorporation of the liposomes into rat liver microsomal
      membranes, membrane fluidity was quantitated by measuring changes in
      polarization. Membranes exhibited a greater sensitivity to peroxidation than
      cholesterol in that incorporation of peroxidized liposomes induced microsomal
      membrane rigidity substantially more than did cholesterol-loaded liposomes. Thus
      it is proposed, based on data from the present and earlier studies, that membrane
      fluidity can be modulated readily by lipid peroxidation of membrane
      phospholipids, irrespective of the influences of cholesterol. These results
      support the proposal that alterations of lipid structure are more potent and
      effective than compositional changes in cholesterol in inducing age-related
      increases in membrane rigidity.

PMID- 7628734
TI  - Radiation-induced clastogenic factors: anticlastogenic effect of Ginkgo biloba
      extract.
AB  - Clastogenic factors (CFs) were first described in the blood of persons irradiated
      accidentally or for therapeutic reasons. Work of our laboratory has shown that
      they occur also under other circumstances, which are characterized by oxidative
      stress, and that CF-induced chromosome damage is regularly prevented by
      superoxide dismutase (SOD). Recently we found CFs in a high percentage of salvage
      personnel of the Chernobyl reactor accident. These liquidators represent a high
      risk population and might benefit from cancer chemoprevention by antioxidants.
      SOD would have to be injected and is not appropriate for long-term prophylactic
      treatment. In the present study, we therefore evaluated the anticlastogenic
      effect of the Ginkgo biloba extract EGb 761, which is known for its superoxide
      scavenging properties. EGb 761 was tested on CF-treated blood cultures of healthy
      donors. After establishing the optimal protective EGb concentration, using CFs
      produced by irradiation of whole blood from healthy volunteers, the extract was
      tested on cultures exposed to CFs from plasma of persons irradiated as
      liquidators. The anticlastogenic effect could be confirmed for a final
      concentration of 100 micrograms/ml. In 12 consecutive experiments, CFs induced an
      average of 18.00 +/- 4.41 aberrations/100 cells. This was reduced to 7.33 +/-
      3.08 in the parallel cultures receiving 100 micrograms/ml EGb 761 (p < .001). SOD
      was anticlastogenic in the same system at concentrations of 30 cytochrome C
      units/ml (approximately 10 micrograms/ml). Preliminary results obtained in a
      small series of liquidators showed regression or complete disappearance of CFs in
      the plasma after 2 months of treatment with EGb 761 (3 x 40 mg/d).

PMID- 7628736
TI  - The interdisciplinary kiva.

PMID- 7628735
TI  - Oxygen free radicals in rat limbic structures after kainate-induced seizures.
AB  - Several indices of free radical generation were determined in limbic structures
      after kainate (KA)-induced seizure activity in adult and postnatal day (PND) 12
      and 17 rats. Superoxide dismutase, catalase, and glutathione peroxidase
      activities were measured in piriform cortex and hippocampal subfields at 8, 16,
      48 h, and 5 days after KA injection in adults and pups, and also at 3 weeks
      postinjection in adults. KA-induced seizure activity had no significant effect on
      enzyme activities in PND 12 and 17 rats. In adults, superoxide dismutase and
      catalase activities were significantly increased at 5 days after KA
      administration, and returned to preinjection levels by 3 weeks. Glutathione
      peroxidase activity was also increased significantly at 5 days postinjection, but
      remained elevated at 3 weeks. Lipid peroxidation, as indicated by malondialdehyde
      (MDA) concentration, exhibited an early significant increase at 8 and 16 h,
      followed at 48 h and 5 days by a significant decrease. At 3 weeks postinjection,
      MDA levels were still significantly decreased in CA3 and dentate gyrus. KA
      administration in PND 12 and 17 rats had no significant effect on MDA content. KA
      induced seizure activity in adults also resulted in a large and sustained
      increase in protein oxidation in piriform cortex and hippocampus. The early
      increase in MDA and protein oxidation in adult rats strongly suggests the
      involvement of oxygen free radicals in the initial phases of KA-induced
      pathology, whereas the changes in scavenging enzyme activities and MDA content at
      5 days and 3 weeks post KA injection possibly reflect glial proliferation
      subsequent to neuronal death.

PMID- 7628737
TI  - Notes from the 1995 White House Conference on Aging.

PMID- 7628738
TI  - A community-based breast cancer education and screening program for elderly
      women.

PMID- 7628739
TI  - Perceived stressors of financially secure, community-residing older women.

PMID- 7628740
TI  - Alzheimer's disease: assessing safety problems in the home.

PMID- 7628741
TI  - Assisted living: challenges for nursing practice.
AB  - There can be no doubt about that, as the elderly population increases, there is a
      need to provide alternative models of housing and health care. The elderly have
      become a vocal group, defining their needs and demanding their rights. New models
      of care, such as assisted living, allow elders to age in place, and nurses are
      called upon to adapt to the challenges of practice. We need to be responsive to
      the changing needs of the elderly population, to alter the directive focus of our
      practice to a more assistive model, and we must look at our practice itself to
      determine what changes need to take place to promote aging with maximum
      independence.

PMID- 7628742
TI  - Parkinsonism: an overview.

PMID- 7628743
TI  - Creating functional environments for elder care facilities.

PMID- 7628744
TI  - Assessment of social networks and isolation in community-based elderly men and
      women.

PMID- 7628745
TI  - Health promotion and disease prevention in home care.

PMID- 7628746
TI  - What elders think about food.

PMID- 7628747
TI  - Tamoxifen for the prevention of breast cancer.

PMID- 7628748
TI  - Posttraumatic stress in an older population.

PMID- 7628749
TI  - Engraftment kinetics and long-term stability of hematopoiesis following
      autografting of peripheral blood stem cells.
AB  - BACKGROUND: We analyzed short-term and sustained hematopoietic reconstitution
      after high-dose therapy with peripheral blood stem cell (PBSC) support in
      patients with various malignant disorders. METHODS: Fifty-six patients, all with
      malignant hematologic disorders, were autografted between 1989 and 1994 using
      PBSC (47 pts) or PBSC + bone marrow (BM) cells (9 pts). PBSC were collected after
      mobilization with chemotherapy +/- hematopoietic growth factors (GF). RESULTS:
      All patients engrafted > 0.5 x 10(9)/L polymorphonuclear cells (PMN) and > 50.0 x
      10(9)/L Plt at a median of 12 (8-32) and 13 (9-365) days, respectively. Thirty
      nine patients were evaluable for long-term graft performance, and their
      hematologic values at 30 and 100 days, at 6 months and at 1, 2, 3, 4 and 5 years
      were retrospectively analyzed. Steady counts were recorded over the years. None
      of the patients had late graft failure. CONCLUSIONS: PBSC given after high-dose
      chemotherapy ensure a fast hematologic recovery with stable graft performance up
      to five years after autograft. Though this is not definitive proof of the
      presence of uncommitted stem cells in the PBSC population, it gives further
      support to the idea that PBSC are as safe as bone marrow for long-term
      engraftment. A delayed or incomplete recovery of platelets may occur with low
      PBSC counts or when disease relapse occurs rapidly after autograft.

PMID- 7628750
TI  - Abnormal neutrophil chemotaxis in bone marrow transplant patients correlates with
      impaired 31D8 monoclonal antibody binding.
AB  - BACKGROUND: 31D8 monoclonal antibody (mAb) has been shown to bind heterogeneously
      to human neutrophils, identifying subsets of cells which differ in their
      functional response to chemotactic stimuli. In this study we used 31D8 mAb to
      determine whether differences in neutrophil subpopulations might explain the long
      lasting decreased chemotaxis observed in bone marrow transplant recipients.
      METHODS: Thirty patients with self-sustaining hematopoiesis 1 to 5 years bone
      marrow transplantation (BMT) (15 allogeneic and 15 autologous) performed for
      acute lymphocytic leukemia (ALL, 10 patients) or acute myelogenous leukemia in
      complete remission (8 patients), Hodgkin's lymphoma (2 patients), chronic myeloid
      leukemia (8 patients) and severe aplastic anemia (2 patients) were included in
      the study. Neutrophil chemotaxis was evaluated using a modified Boyden chamber
      assay and 31D8 binding was determined by indirect immunofluorescence and
      cytofluorimetric analysis. RESULTS: Neutrophil chemotaxis was significantly
      impaired in the BMT group with respect to controls. The chemotactic defect
      strikingly correlated with autologous BMT and, in particular, with ALL as the pre
      existing disease. No differences between patients and controls were observed in
      the percentage of 31D8 bright and dull neutrophils. However, when mean
      fluorescence intensity (MFI) was analyzed as a relative measure of 31D8 antigen
      expression on the overall neutrophil population, a significant decrease was
      observed in neutrophils from BMT patients with respect to controls. As for
      chemotaxis, the impairment of 31D8 binding was more evident in autologous BMT and
      strikingly correlated with ALL as the pre-existing disease regardless of age, sex
      and time since BMT. Moreover, a significant positive correlation between impaired
      chemotaxis and decreased 31D8 binding was found in our patients. CONCLUSIONS:
      These findings suggest that the decreased neutrophil chemotaxis observed in some
      BMT patients may be due in part to circulating 31D8 dull neutrophils, although
      the causes for the decreased 31D8 binding and for the quite pronounced neutrophil
      defect in ALL patients remain unknown.

PMID- 7628752
TI  - Single-institution results of autologous bone marrow transplantation in acute
      myeloid leukemia.
AB  - BACKGROUND: Current results of autologous bone marrow transplantation (ABMT)
      suggest that this procedure may prolong disease-free survival (DFS) in patients
      with acute myeloid leukemia (AML). MATERIALS AND METHODS: Over the last ten
      years, 29 AML patients received unpurged autologous bone marrow (BM) after a
      conditioning regimen including Ara-C (3 g/m2/12h, days -9, -8), CTX (60
      mg/kg/day, days -6, -5) and TBI (3.33 Gy/day, days -3 through -1). In 21
      patients, ABMT was performed as late intensification after first CR. Eight more
      relapsing patients were autografted after the achievement of second CR. RESULTS:
      Three patients died from transplant-related complications. In the remaining
      patients, mean times to WBC and platelet recovery were, respectively, 23 days
      (range 13-55) and 55 days (range 22-790). Follow-up for censored patients ranged
      from 1 to 120 months. Relapse occurred in 7 patients (5 in first and 2 in second
      CR). Overall 5-year DFS and event-free survival (EFS) chances were, respectively,
      67.3% and 60%, with no statistically significant differences between first (DFS =
      67.3%, EFS = 60.3%) and second CR (DFS = 68.6%, EFS = 60%). DISCUSSION: Apart
      from obvious selection biases, our study suggests that outcome in first CR AML
      patients is improved by ABMT. Long-term DFS and EFS are clearly better than when
      conventional post-remission chemotherapies are used. The greater antileukemic
      potential of ABMT is further underlined by the results in patients autografted in
      second CR, when conventional chemotherapy is almost never curative.

PMID- 7628751
TI  - The treatment of acute myeloid leukemia in Brazil: progress and obstacles.
AB  - BACKGROUND: Substantial progress has been made in the treatment of acute myeloid
      leukemia in the last two decades. We wanted to evaluate the outcome of intensive
      chemotherapy and the influence of recent therapy changes in underprivileged
      patients treated in a large urban public university hospital. METHODS: The
      records of all patients treated for acute myeloid leukemia from 1980 to 1993 were
      analyzed. RESULTS: 109 patients were identified; 41 did not receive any treatment
      for the leukemia because of infectious and/or hemorrhagic complications of
      advanced disease. Median survival in this group was 4 days. The other 68 patients
      received one of two induction protocols: TAD from 1980 to 1985 (n = 23) and ara-C
      plus daunorubicin from 1985 to 1992 (n = 45). The complete remission rate was
      56%, disease-free survival 24% and overall survival 15% at 13 years. Overall
      survival was better for patients treated with ara-C plus daunorubicin than with
      TAD (19% versus 8%, p = 0.01). This is attributed to a reduction in infection
      mortality after ceftazidime and amikacin replaced cephalotin, carbenicillin and
      amikacin as the antibiotic regimen. CONCLUSIONS: The most effective intervention
      in our population would probably be an improvement in the primary health care
      system, so that earlier diagnosis could allow the treatment of a larger fraction
      of patients.

PMID- 7628753
TI  - The PML/RAR alpha fusion gene in the diagnosis and monitoring of acute
      promyelocytic leukemia.
AB  - The acute promyelocytic leukemia (APL)-specific t(15;17) chromosome abnormality
      is characterized at the molecular level by rearrangement of the PML and RAR alpha
      genes, resulting in fusion PML/RAR alpha mRNA and a chimeric protein. Besides its
      relevance in the pathogenesis of the disease, this hybrid gene represents a
      specific tumor marker that is rapidly detectable by reverse transcriptase
      polymerase chain reaction (RT-PCR) in the RNA extracted from leukemic blasts.
      Several studies have highlighted the clinical relevance of PML/RAR alpha
      detection, which provides a specific diagnosis, prognostic information, and
      prediction of relapse when monitoring residual disease during the follow-up. In
      fact, this hybrid gene is detected in 100% of APLs. Rare cases of patients with a
      morphological diagnosis of FAB M3 AML who lack the specific PML/RAR alpha
      abnormality have been reported as being unresponsive to differentiation
      treatment. Finally, all the studies reported so far on PCR monitoring in APL have
      documented that the identification of small amounts of residual disease at
      remission strongly predicts impending relapse. Thus, RT-PCR of the hybrid PML/RAR
      alpha gene is currently performed prospectively as part of cooperative clinical
      trials aimed at better addressing post-remission treatment in APL.

PMID- 7628754
TI  - Leukocyte CD11/CD18 integrins: biological and clinical relevance.
AB  - The integrin family consists of a series of related alpha beta heterodimers
      (subunits of 95,000-200,000 Mw) involved in a variety of cell-matrix and cell
      cell adhesion functions. Leukocyte adhesion has biological importance in numerous
      processes involving host defense. The CD11/CD18 integrins are differentiated
      antigens which play a critical role in this mechanism. CD11a/CD18 are apparent on
      early progenitors of all myeloid and erythroid cells. CD11b/CD18 and CD11c/CD18
      are more restricted antigens normally expressed on monocytes, macrophages, PMN
      and natural killer cells. Activated granulocytes and monocytes express far more
      CD11b/CD18 than the other two antigens: 6 to 8 x 10(5) CD11b/CD18 molecules
      appear on maximally activated granulocytes. These integrins and in particular the
      beta 2 subunit are lacking in a genetic disease. On the other hand, they are
      fundamental in numerous physiological processes and in various hematological and
      cardiovascular diseases. The biochemical characterization and behavior of the
      CD11/CD18 complex in various clinical conditions are the subject of this review.

PMID- 7628755
TI  - Prognostic features and therapeutical approaches in B-cell chronic lymphocytic
      leukemia: an update.
AB  - In the past few decades important progress has been made in the understanding of
      chronic lymphocytic leukemia (CLL). Indeed, systematic studies of natural history
      and prognostic factors have made it possible to predict the outcome of disease.
      Although clinical stage (i.e. Rai and Binet stages) is the strongest predictor of
      survival, additional prognostic parameters, including patterns of bone marrow
      (BM) infiltration, lymphocyte doubling time (LDT), immunophenotype and
      cytogenetics, have now been identified. Furthermore, criteria of smoldering CLL
      (i.e. stage A, low lymphocyte count, non-diffuse BM histology, relatively high
      hemoglobin level, LDT > 12 months) allow identification of a subgroup of patients
      with indolent course and good prognosis for whom treatment should be delayed,
      unless progression occurs. Recent meta-analysis of clinical trials has
      demonstrated no survival advantage for immediate versus referred treatment in low
      clinical stages. The same considerations apply when comparing combination versus
      single-drug regimens. Purine analogues like fludarabine, 2'-chlorodeoxyadenosine
      and 2'-deoxycoformicin are active in CLL. Data on these drugs come from
      uncontrolled clinical trials; randomized studies are in progress. In addition,
      some issues concerning the relationship between response and survival, cross
      resistance between purine analogues and eradication of the CLL clone, remain
      still unresolved. There are also increasing data on bone marrow transplants in
      CLL, although the high treatment-related mortality suggests that this procedure
      may have some benefit only in selected refractory young CLL patients with adverse
      features. This review will focus on recent progress in the prognosis and therapy
      of CLL. Issues that remain controversial will be a matter of discussion.

PMID- 7628756
TI  - Ocular involvement in acute thrombotic thrombocytopenic purpura.

PMID- 7628757
TI  - Prevention of polymorphonuclear leukocyte agglutination in vitro.

PMID- 7628758
TI  - Neuropathies associated with monoclonal gammapathies.

PMID- 7628760
TI  - Basic, Laboratory and Clinical Aspects of Venous Thromboembolism. Proceedings of
      the 1st Winter Meeting on Coagulation. Cortina d'Ampezzo, Italy, March 9-12,
      1994.

PMID- 7628759
TI  - Bcl-2 oncoprotein expression in acute myeloid leukemia.
AB  - BACKGROUND: In lymphoproliferative diseases the expression of Bcl-2, a
      mitochondrial oncoprotein capable of blocking apoptosis, is well-documented,
      while little research has been carried out on its distribution in
      myeloproliferative conditions. METHODS: Using immunocytochemical methods, 63
      cases of acute myeloid leukemia (AML) at onset and 10 relapses were studied to
      investigate Bcl-2 expression and any possible correlations with subtypes of the
      FAB classification, sex, age or white cell peripheral blood count at onset.
      RESULTS: Bcl-2 is present in 87.3% of AML cases at onset and in 100% of relapses.
      In 68.3% of cases at onset and in 90% of relapses the protein is present in more
      than 20% of the blasts. Relapses always show higher percentages of positive
      expression than those seen at onset. Our results demonstrate no statistical
      correlations between the expression of the oncoprotein Bcl-2 and FAB subtypes,
      sex, age, or white cell peripheral blood count. CONCLUSIONS: The majority of
      blasts from AML patients express the oncoprotein Bcl-2, which is able to protect
      leukemic cells from apoptosis. Since numerous chemotherapies are cytotoxic in
      that they induce apoptosis, we feel that in vitro studies of cells from AML
      patients are necessary in order to broaden our knowledge about the effects of the
      most common therapeutic drugs and of those substances which, alone or in
      association, can modulate Bcl-2 expression.

PMID- 7628761
TI  - Preanalytical aspects of coagulation testing.

PMID- 7628762
TI  - Inherited resistance to activated protein C, a major basis of venous thrombosis,
      is caused by deficient anticoagulant cofactor function of factor V.

PMID- 7628763
TI  - Autoimmune protein S deficiency: a disorder predisposing to thrombosis.

PMID- 7628764
TI  - Antiphospholipid antibodies, lupus anticoagulants and thromboembolic disease.

PMID- 7628765
TI  - Autoimmune antiphospholipid antibodies: what is their true target?

PMID- 7628766
TI  - Antiphospholipid antibodies, hypercoagulability and thrombosis.

PMID- 7628767
TI  - Research and development strategies in hemostasis and thrombosis.

PMID- 7628768
TI  - The pathogenesis of venous thromboembolism.

PMID- 7628769
TI  - The epidemiology of deep vein thrombosis and pulmonary embolism.

PMID- 7628770
TI  - Symptomatic deep-vein thrombosis and the post-thrombotic syndrome.

PMID- 7628771
TI  - Inflammation and thrombosis: the impact of inflammation on the protein C
      anticoagulant pathway.

PMID- 7628772
TI  - The value of laboratory tests in the diagnosis of venous thromboembolism.

PMID- 7628773
TI  - Cost-effectiveness of post-routine screening for an occult cancer in patients
      with idiopathic venous thromboembolism.

PMID- 7628774
TI  - Prophylaxis of venous thromboembolism: the old and the new.

PMID- 7628775
TI  - Standardization of the prothrombin time: clinical results with a recombinant
      tissue factor reagent.

PMID- 7628776
TI  - Treatment of venous thromboembolism: unfractionated heparin or low molecular
      weight heparins?

PMID- 7628777
TI  - Selected strategies in venous thromboembolism: local thrombolytic treatment and
      caval filters.

PMID- 7628778
TI  - Oral anticoagulants: old drugs with a promising future.

PMID- 7628779
TI  - [The effect of cell environment on osteoblastic function].
AB  - The effect of cell environment on osteoblastic function was described in this
      review article. Hypocalcemia, hypocalcified dentin and inhibition of bone
      formation were demonstrated in rats fed a low calcium diet. These phenomena led
      us to hypothesize that a low-calcium environment must be one of the important
      factors to induce the inhibition of bone formation. This proposed mechanism was
      verified in an in vitro experiment. In the rat neonatal femur cultured in a low
      calcium medium, the head size of the femur, full longitudinal length of the femur
      and total hexosamine content increased. Alkaline phosphatase activity,
      chondroitin sulfate synthesis and DNA synthesis activity increased, but proline
      synthesis activity decreased. In the calvarial bone cells, the total calcium, IP3
      contents and PKC activity decreased, but the sensitivity of the cell membrane to
      a stimulation was enhanced. In mouse osteoblastic MC3T3-E1 cells, c-fos mRNA
      expression increased after the treatment with fetal bovine serum (FBS) or
      epidermal growth factor (EGF), and the degree of increase was highest with the 30
      min treatment period in both FBS- and EGF-treated cells. The expression was
      significantly higher in the low Ca group as compared to the control group (P <
      0.01). From these results, it was suggested that tha femur and osteoblasts react
      to restore the normal cell function against a low-calcium environment, the
      mediating and intracellular signal transduction system, and a transcriptional
      activity at the gene level.

PMID- 7628780
TI  - [Inhibitory effects of bisphosphonates on bone resorption].
AB  - Bisphosphonates have a P-C-P bond instead of the P-O-P bond of inorganic
      pyrophosphate that makes them resistant to enzymatic degradation and gives them a
      high affinity for hydroxyapatite. They are potent blockers of osteoclastic bone
      resorption and have been successfully used to treat metabolic bone diseases that
      involve increased bone resorption. It is possible to synthesize a variety of
      bisphosphonates by substituting the hydrogen on the carbon atom. The
      pharmacological characteristics and activity varies greatly from compound to
      compound, ranging from 1 to 10,000. Some structure-activity relationships have
      been found, but no clear-cut one has been established yet. There is a general
      consensus that the inhibition of bone resorption by bisphosphonates is not caused
      by the inhibition of dissolution of the hydroxyapatite crystal, but is actually
      caused through a cellular mechanism that is not completely understood. In the
      present review article, the possible mode of bisphosphonate action was discussed
      with special reference to: (1) whether bisphosphonates inhibit the function of
      mature osteoclasts directly or through osteoblasts and (2) whether
      bisphosphonates inhibit the proliferation or differentiation of osteoclast
      progenitors to osteoclasts.

PMID- 7628781
TI  - [Physiology and pharmacology of hard tissues--effect of chemicals on the
      formation and the resorption mechanism of tooth and bone].
AB  - This review described the effects of several drugs on the formation and the
      resorption mechanism of tooth and bone. The enamel formed during high fluoride
      exposure showed marked hypocalcification, and the organic substances appeared on
      the incisors in these regions. Such changes following fluoride administration
      appear to indicate an inhibition of the mineral deposition and/or an inhibition
      of organic matrix withdrawal. The successive bisphosphonate (HEBP) injections
      reduced both the progress of the mineral deposition and the formation of the
      enamel matrix. Colchicine showed a remarkable inhibitory effect on the matrix
      forming cells of the dentin and enamel in teeth through its striking inhibitory
      action on the cytoskeletal system and secretary function. The dentin formation in
      rabbit and rat incisor dentin was reduced markedly. Colchicine induced reparative
      dentinogenesis in dental pulp and ectopic calcification in the bone marrow. Both
      sodium salicylate and aspirin reduced dentin formation through a mechanism that
      reduces the incorporation of collagen precursors into odontoblasts. Sodium
      salicylate also inhibited the growth of the upper jaw and tibia in rats. The
      recruitment of osteoclast-like multinucleated cells was inhibited by sodium
      salicylate in vitro. A pharmacological approach for studying the formation and
      resorption mechanism of hard tissue is useful tool for developing hard tissue
      research.

PMID- 7628782
TI  - [Experimental periodontitis in rats].
AB  - ODU Plaque-susceptible rats (ODUS/Odu) exhibit markedly heavy plaque formation in
      the lower incisors and develop both periodontal pockets and gingivitis after
      being fed a commercially available powder diet. These rats have been established
      as an inbred strain. We have demonstrated that the ODUS/Odu are a very suitable
      experimental model for studying periodontitis. We already reported about the
      allelic distribution, changes of plaque formation and body weight, biochemical
      nature, toxic activity, vascular permeability factor and bradykinin inactivating
      factor of the plaque, histological and immunological studies, the pH in the
      periodontal pocket, amount of saliva, IgA in the saliva, salivary kallikrein, the
      relationship between sialic acid in the saliva and the serum, leukocyte functions
      (chemotaxis and superoxide anion) in ODUS/Odu, histamine, mast cell, free
      radicals, superoxide dismutase activities in gingiva and gingival nerve fibers
      with substance P or calcitonin gene-related peptide, and effect of diabetes.
      Streptozotocin-induced diabetic ODUS/Odu may be a useful tool for studying the
      pathological mechanisms in the development of periodontal tissue breakdown in
      diabetes. ODUS/Odu should help to further establish the utility of this strain as
      a model for experimental periodontal disease.

PMID- 7628783
TI  - [Pharmacological study of tooth formation and mineralization using a tooth germ
      cultivation system].
AB  - In this study, we introduce a cultivation method for mandibular first molars from
      mouse embryos. We also investigate the in vitro effects of several drugs on tooth
      formation. Histological observations demonstrated that the tooth germ dissected
      from 17-day-old embryonic mice and cultivated for 7 days under the conditions
      described here showed clear mineralization in the dentin and enamel. Alkaline
      phosphatase (ALP) activity and calcium content in the tooth germ increased
      developmentally during 7-day cultivation. The increase of calcium was preceded by
      that of ALP in the germ. The removal of ALP attached covalently to the external
      surface of plasma membranes by phosphatidylinositol specific phospholipase C
      disturbed in vitro mineralization in the tooth germ, suggesting that ALP
      functioning as an ectoenzyme is involved in the physiological process of tooth
      formation. To elucidate the effects of calcium regulating hormones and several
      drugs on tooth mineralization, ALP and calcium content were measured and also the
      tooth germ was observed histologically. The results obtained from the present
      study suggest that this in vitro system provides a useful tool for investigating
      both the direct action of drugs on tooth formation and the mechanisms of drug
      action.

PMID- 7628784
TI  - [Studies on periodontal pathogenic proteinases from Porphyromonas gingivalis and
      host cells].
AB  - Progressive periodontal disease is characterized by acute progressive lesions of
      gingival connective tissues, excessive leukocyte infiltration, and occurrence of
      a characteristic microflora. A variety of proteolytic enzymes derived from oral
      bacteria and host cells are found in gingival crevices and thought to play an
      important role in the onset and development of progressive periodontal disease.
      The anaerobic bacterium Porphyromonas gingivalis has been implicated in the
      etiology of the disease. Recently, we have purified a novel arginine-specific
      cysteine proteinase, termed "argingipain", from the culture supernatant of the
      organism. The enzyme was shown to have two important abilities related to the
      virulence of the organism. One is direct association with periodontal tissue
      breakdown through its abilities to degrade physiologically important proteins
      such as human collagens (type I and IV) and to evade inactivation by internal
      protease inhibitors. The other is associated with disruption of the normal host
      defense mechanisms through its abilities to degrade immunoglobulins and to
      inhibit the bactericidal activity of polymorphonuclear leukocytes. The virulence
      of argingipain was further substantiated by disruption of argingipain-encoding
      genes on the chromosome by use of suicide plasmid systems. On the other hand, we
      have studied roles of host cell-derived proteinases in the periodontal tissue
      breakdown. Levels of lysosomal proteinases such as cathepsins B, H, L, G and
      medullasin were determined in gingival crevicular fluid from periodontitis
      patients and experimental gingivitis subjects by activity measurement and
      sensitive immunoassay. The results suggested that all of these enzymes would be
      involved in the development of both gingivitis and periodontitis.

PMID- 7628785
TI  - [Effects of thunberginol A contained in Hydrangeae dulcis forium on types I-IV
      allergies].
AB  - The inhibitory actions of thunberginol A on anti-allergic (type I-IV) activity
      were examined. Oral administration of thunberginol A 2 hr before the challenge
      significantly inhibited the PCA reaction (type I) in rats at a dose of more than
      300 mg/kg and the ear PCA reaction in mice at a dose of more than 50 mg/kg.
      Thunberginol A at a dose of more than 300 mg/kg also significantly inhibited the
      allergic bronchoconstriction in rats. Thunberginol A concentration-dependently
      (10(7)-10(-4), 10(-5)-10(-4) M) inhibited the allergic contractions of rat
      trachea sensitized with IgE and those of the guinea pig lung preparation
      sensitized with IgG. It also inhibited the allergic histamine release from
      sensitized peritoneal exudate cells in a concentration-dependent manner (10(-5)
      10(-4) M). Thunberginol A had anti-serotonic activity on the contraction of
      smooth muscle, and it increased the ear vascular permeability in mice.
      Thunberginol A significantly inhibited the primary response of contact dermatitis
      (type IV) in mice at 100 mg/kg from the day after immunization to the day before
      challenge, and it also inhibited the delayed type foot pad swelling in mice at a
      dose of more than 300 mg/kg at 0 and 8 hr after the challenge. These findings
      suggest that orally administered thunberginol A is effective against type I and
      type IV allergy.

PMID- 7628786
TI  - [Vasodilating effects of NY-008 in ring preparation of rat aorta].
AB  - Vasodilating effects of NY-008 were compared to those of verapamil in isolated
      rat aorta. NY-008 at the dose of 3 x 10(-5) M relaxed 10-70 mM potassium chloride
      (KCl)-induced contraction. NY-008 relaxed preparations precontracted with 60 mM
      KCl concentration-dependently with an IC50 of (6.17 +/- 1.75) x 10(-6) M, and
      those precontracted with norepinephrine (NE) (10(-6) M) concentration
      dependently, maximally by 90.0 +/- 2.86%, with an IC50 of (2.06 +/- 0.38) x 10(
      5) M. At 10(-8)-3 x 10(-6) M, verapamil relaxed preparations precontracted with
      NE (10(-6) M) concentration-dependently, maximally by 55.9 +/- 5.56%. At 3 x 10(
      5) M and 10(-4) M, NY-008 relaxed (10(-6) M)-induced phasic contractions in a
      Ca(2+)-free 1 mM EGTA-containing buffer, by 22.4 +/- 3.69% and 35.4 +/- 5.74%,
      respectively. In contrast, 3 x 10(-7) M verapamil did not. NY-008 concentration
      dependently decreased the maximal responses to calcium chloride (CaCl2) in 60 mM
      KCl-depolarized preparations, and it shifted the ED50 values of CaCl2 to the
      right, whereas verapamil shifted the ED50 values of CaCl2 to the right without
      decreasing the maximal responses to CaCl2. At 10(-5)-3 x 10(-4) M, NY-008
      concentration-dependently relaxed preparations precontracted with prostaglandin
      F2 alpha (10(-5) M) in a Ca(2+)-free, 0.5 mM EGTA-containing buffer, whereas 10(
      7)-10(-5) M verapamil did not. These results suggest that NY-008 antagonized Ca2+
      and decreased the Ca(2+)-sensitivity of contractile elements or inhibited
      contractile proteins in rat aorta.

PMID- 7628787
TI  - [The effect of lactitol (NS-4) on the concentrations of ammonia and amino acids
      in blood and cerebrospinal fluid in Eck fistula (portacaval-shunted) dogs].
AB  - Lactitol and lactulose were compared in their effect on the concentrations of
      ammonia and amino acids in blood and cerebrospinal fluid (CSF) in Eck fistula
      dogs. Drugs were administered intragastrically for four weeks from three weeks
      after the portacaval-shunt operation. The concentration of ammonia in the blood
      and CSF had increased three- to five-fold three weeks after the operation and
      increased gradually thereafter. Eck fistula dogs showed a characteristic profile
      of plasma amino acids, with increased concentrations of tryptophan (Trp) and
      aromatic amino acids (AAA) and reduced concentrations of branched-chain amino
      acids. The profile of CSF amino acids revealed substantial increases in the
      concentrations of AAA as well as glutamine (Gln), Trp and glutamic acid. Lactitol
      at doses of 1 and 3 g/kg/day significantly decreased the ammonia concentration in
      both the blood and CSF after administration for two and four weeks. Lactitol at a
      dose of 3 g/kg/day significantly decreased the concentration of Trp in the plasma
      and the concentrations of valine, leucine, AAA and Gln in CSF. Lactulose showed
      effects similar to those of lactitol. These findings suggest that lactitol may be
      a promising agent for the clinical treatment of hyperammonemia and hepatic
      encephalopathy, since it decreased the concentration of ammonia in the blood and
      CSF and the elevated concentrations of AAA in CSF associated with the development
      of hepatic encephalopathy.

PMID- 7628788
TI  - [Ameliorating effect of lactitol on experimental hepatic encephalopathy in Eck
      fistula dogs].
AB  - Eck fistula (portacaval shunted) dogs were prepared for use as an experimental
      model of chronic hepatic encephalopathy. The effect of lactitol on hepatic
      encephalopathy was investigated by observing the behavior, electroencephalograms
      (EEGs) and visually evoked potentials (VEPs) of the experimental dogs. Lactitol
      was administered intragastrically once a day for 12 weeks from the third week
      after the portacaval-shunt operation and the behavior, EEGs and VEPs of the dogs
      were observed every two weeks. Dogs not given lactitol became sluggish, then
      apparently blind, and eventually fell into a coma, over a period of several weeks
      after the operation. Some dogs died. The EEGs revealed low-voltage slow waves
      and, at a later stage, displayed flattening in some dogs. The VEPs displayed
      prolonged latency of both the positive and the negative component as well as an
      increased amplitude. Lactitol at 1 or 3 g/kg/day suppressed the behavioral
      symptoms and the changes in the EEGs and the VEPs. These results suggest that
      lactitol may be useful for the treatment of various nervous symptoms in patients
      with hepatic encephalopathy accompanied by hyperammonemia.

PMID- 7628789
TI  - Heterocyclic amine content in fast-food meat products.
AB  - Heterocyclic aromatic amines are sometimes formed during the cooking of muscle
      meats, and their mutagenic and carcinogenic effects are of potential concern in
      the aetiology of human cancer. In a large survey of the heterocyclic amine
      content of foods, fried or charbroiled hamburgers, fried chicken, chicken breast
      sandwiches, fish sandwiches and breakfast sausages were purchased from fast-food
      restaurants. At least three different chains were visited per product and samples
      from five stores from each chain were pooled. The solid-phase extraction and HPLC
      method was used to analyse pooled samples for heterocyclic amine content and
      mutagenic activity with the Ames/Salmonella assay. Samples were analysed in a
      blind study which also contained quality control samples of two types, one high
      and one low in heterocyclic amine content and mutagenic activity. Results from
      the fast-food products showed undetectable levels of heterocyclic amines in 10 of
      17 samples and only low levels [< or = 1 ng/g total of 2-amino-3,8
      dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-1-methyl-6-phenylimidazo[4,5
      b]pyridine (PhIP) and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx)]
      in the remaining samples. Compared with literature values based primarily on
      laboratory and home cooking conditions, fast-food meat products appear to
      contribute only a small percentage of the estimated daily dietary intake of
      heterocyclic amines.

PMID- 7628790
TI  - Effect of acute administration of fish oil (omega-3 marine triglyceride) on
      gastric ulceration and secretion induced by various ulcerogenic and necrotizing
      agents in rats.
AB  - The fish oil commercially known as Marine-25 (omega-3 marine triglyceride) is an
      eicosapentaenoic acid (EPA)-rich oil. It was investigated for its ability to
      inhibit gastric secretion and to protect the gastric mucosa against the injuries
      caused by pyloric ligation, non-steroidal anti-inflammatory drugs (NSAIDs-
      aspirin and indomethacin), reserpine, hypothermic restraint stress and
      necrotizing agents [0.6 M HCl 0.2 M NaOH or 80% (v/v) aqueous ethanol]. The
      results showed that the fish oil, at a dose of 5 or 10 ml/kg body weight,
      provided significant protection in the various experimental models used. It
      produced a significant inhibition of gastric mucosal damage induced by pyloric
      ligation, NSAIDs, reserpine or hypothermic restraint ulcers. Fish oil also
      exerted a significant inhibitory action on gastric mucosal lesions produced by
      various necrotizing agents. Our findings show that fish oil rich in
      eicosapentaenoic acid possesses both antisecretory and antiulcerogenic effects.

PMID- 7628791
TI  - Reversibility of manganese-induced learning defect in rats.
AB  - In this study the mechanism by which manganese (Mn) induces learning defect and
      its reversibility has been investigated in rats. Female albino rats were dosed
      orally with 357 micrograms Mn/kg body weight for 15 or 30 days. Attempts were
      made to correct the Mn-induced learning defect by (1) co-administration of
      mevinolin and Mn for 30 days; (2) administration of mevinolin for 15 days after
      15 days of dosing with Mn, and (3) by withdrawal of Mn treatment (15 days dosing
      with Mn followed by 15 days without Mn). Mevinolin was given orally at 235.7
      micrograms/kg body weight. Significant increases in the Mn and cholesterol levels
      in the hippocampus were accompanied by an obvious slowness in learning of rats
      exposed to Mn. After one training period (day 29) the time required to reach the
      exit of a T-maze was 104.5 +/- 13.8 sec for rats dosed with Mn for 30 days,
      whereas that of the controls was 28.7 +/- 11.4 sec on day 30. This delay was
      completely corrected (to 30.7 +/- 6.0 sec) in rats co-administered mevinolin (an
      inhibitor of cholesterol biosynthesis) with Mn. Withdrawal of Mn, with or without
      inhibiting the cholesterol biosynthesis, also corrected the Mn-induced learning
      defect. These results suggest that Mn toxicity produces learning disability by
      increasing cholesterol biosynthesis and this reversible disability in learning
      can be corrected by withdrawal of Mn exposure.

PMID- 7628792
TI  - Effects of drinking pattern on the peak/trough blood concentrations in drinking
      water studies.
AB  - The effects of changes in drinking patterns on the expected peak/trough blood
      concentrations of test compounds were examined during rodent dosed drinking water
      studies. They were based on the assumption that the kinetics of the test compound
      is linear and time-invariant. Results indicate that drinking patterns have minor
      effects on the expected peak/trough concentrations and the time to reach these
      concentrations. If a 12-hr light/dark cycle starting at 7.00 is used for all the
      drinking patterns studied, the peak and trough concentrations will occur in the
      early morning and late afternoon, respectively. A comparison of the predicted
      versus experimentally determined pentachlorophenol (PCP) plasma concentrations in
      a 1-wk rat drinking water study revealed that using a circadian rhythm drinking
      pattern in the model generated the most satisfactory prediction. Predictions
      based on a square wave drinking pattern with 90% drinking activities in the night
      phase were also excellent. Triangular or sinusoidal drinking patterns were least
      accurate in predictions.

PMID- 7628793
TI  - Carcinogenicity of policosanol in mice: an 18-month study.
AB  - Policosanol (trade name Ateromixol) is a new cholesterol-lowering drug that has
      been isolated and purified from sugar cane wax. The effects of policosanol (50
      500 mg/kg) administered orally for 18 months to male and female Swiss mice were
      investigated. No differences in daily clinical observations, weight gain, food
      consumption and mortality (survival analysis) between groups were found.
      Histopathological study showed that the frequency of neoplastic (benign and
      malignant) lesions was similar in the control and policosanol-treated groups. The
      lesions observed were similar to the spontaneous lesions in Swiss mice reported
      in previous studies. As no drug-related increase in the occurrence of malignant
      or benign neoplasm was found, nor acceleration in tumour growth in any specific
      group observed, this study shows no evidence of policosanol-induced
      carcinogenicity in Swiss mice.

PMID- 7628794
TI  - Calcium accumulation in experimental hypertension.
AB  - At present, the significance of calcium accumulation in the aetiology of coronary
      artery disease (CAD) in humans is not known, except only to exacerbate the
      condition. In an attempt to understand ionic disturbances in vasculature derived
      from cardiovascular abnormalities, soft tissues from hypertensive models were
      examined. The study hypothesis was to see if basic cardiovascular regulatory
      sites in hypertensive models accumulated greater amounts of Ca2+. Calcium levels
      were measured by flame atomic absorption spectrophotometry in tissue derived from
      two types of hypertensive rabbits. Both models of hypertension developed mean
      arterial pressures of at least 50 mm Hg greater than those of controls over a 5
      wk period. Significant increases in calcium levels were found in left ventricle
      and aorta derived from both hypertensive groups compared with controls. Renal
      cortex and medulla were not significantly different among any of the groups.
      These levels corroborate the findings of others which show increased calcium
      levels in cardiovascular tissues in experimental hypertension in rabbits.
      Although there have been several studies that have shown the relationship between
      calcium, hypertension and CAD, this is the first study to look at calcium
      accumulation rather that the effects of calcium channel blockers. The link
      between hypertension and calcium accumulation in a number of tissues may be
      important in the development of CAD and other cardiac dysfunction.

PMID- 7628795
TI  - Toxicokinetics of the mycotoxin fumonisin B2 in rats.
AB  - Fumonisin B2 (FB2), a secondary metabolite of the fungus Fusarium moniliforme,
      was administered at a dose of 7.5 mg/kg body weight to male BD IX rats by ip
      injection or by gavage. FB2 was rapidly absorbed from the peritoneum, its level
      in plasma reaching a maximum within 20 min after injection. It was rapidly
      eliminated from plasma with a half-life of 26 min. After 24 hr, FB2 could not be
      detected in plasma (< 20 ng/ml). Analysis of rat plasma for FB2 following a
      gavage dose failed to detect any toxin over a 6-hr period after dosing. The
      elimination of FB2 in the urine and faeces was determined over a 3-day period
      after dosing. After i.p. injection, the mean urinary excretion over this period
      was 1.2% and faecal elimination accounted for 84.1% of the dose. Similarly, after
      dosing by gavage, 0.2 and 82.0% of the dose was recovered in urine and faeces,
      respectively. FB2 appeared to be excreted unmetabolized.

PMID- 7628796
TI  - Protection by lysosomal hydrolase inhibitors against cytotoxicity of 2
      chloroethylethyl sulfide.
AB  - A possible participation of lysosomal hydrolases in the cytotoxicity of 2
      chloroethylethyl sulfide in spleen lymphocytes was investigated using inhibitors
      of lysosomal phospholipases and proteases. Pepstatin (6 microM) and leupeptin (60
      microM), inhibitors of lysosomal proteases, raised the viability of lymphocytes
      exposed to 2-chloroethylethyl sulfide from 63 to 87 and 88% of control,
      respectively. Serine protease inhibitors showed no significant effect on
      viability. Aminoglycoside inhibitors of lysosomal phospholipases were also found
      to prevent the decrease in viability of spleen lymphocytes exposed to 2
      chloroethylethyl sulfide, and the effectiveness of these aminoglycosides (30
      microM) was as follows: gentamicin > kanamycin > streptomycin, with viability
      increased to 89, 79 and 67%, respectively. In contrast to a co-operative action
      between leupeptin and gentamicin, the protection by pepstatin was reduced in the
      presence of gentamicin. Moreover, the order of the aminoglycosides in terms of
      the extent to which they antagonized the protective action of pepstatin was the
      same as their order of efficacy in preventing the cytotoxicity of CEES. It is
      suggested that inhibitors of lysosomal hydrolases reduce the cytotoxicity of 2
      chloroethylethyl sulfide, presumably through lysosomal stabilization in spleen
      lymphocytes.

PMID- 7628798
TI  - Notes from the school CNEP development and research.

PMID- 7628797
TI  - The characterization of antioxidants.
AB  - The role of antioxidants in nutrition is an area of increasing interest.
      Antioxidants are used (1) to prolong the shelf life and maintain the nutritional
      quality of lipid-containing foods, and (2) to modulate the consequences of
      oxidative damage in the human body. This review discusses what an antioxidant is
      and how the properties of antioxidants may be characterized.

PMID- 7628799
TI  - A cadet's day in the mountains. 1945.

PMID- 7628800
TI  - [Effect of a coplanar PCB on lipid metabolism: the remarkable difference between
      rats and guinea pigs].
AB  - We studied the effect of 3, 4, 5, 3', 4'-pentachlorobiphenyl (PenCB) on lipid
      metabolism by determining the level of triacylglycerol and total cholesterol in
      rats and guinea pigs. Male Wistar rats and male Hartley guinea pigs received
      PenCB in corn oil one at a dose of 25 mg/kg i.p. and 0.5 mg/kg i.p.,
      respectively. Pair-fed control group of both species were treated with the
      vehicle and given the amount of chow matched with that taken by the PenCB-treated
      animals. Free-fed control group was treated with vehicle and was given the chow
      ad libitum. The plasma was collected on the day 5 after the treatment and the
      liver was removed. The plasma triacylglycerol level in guinea pigs treated with
      PenCB was significantly higher than those in free- and pair-fed controls, whereas
      no significant difference was observed in PenCB-treated rats from both control
      groups. The plasma cholesterol level was also higher in PenCB-treated guinea pigs
      than in the two control groups, though the level in rats was significantly lower
      than the corresponding control values. The hepatic triacylglycerol and
      cholesterol levels were increased significantly in both species by the PenCB
      treatment. Although lipid metabolism was disordered in both animals by treatment
      with PenCB, the responsiveness was remarkably different between guinea pigs and
      rats. These differences could be associated with species difference in
      susceptibility toward toxic chlorinated aromatic hydrocarbons.

PMID- 7628801
TI  - [Alteration of peroxisomal enzyme activities in the liver of guinea pigs caused
      by coplanar PCB].
AB  - The hyperlipidemia is a well-known typical symptom in Yusho patients and
      experimental animals treated with PCBs. We have found a significant induction of
      CYP4A1, which catalyzes omega-hydroxylation of fatty acids, in guinea pigs by the
      treatment with a coplanar PCB, 3, 4, 5, 3',4-pentachlorobiphenyl (PenCB), though
      the P450 is reduced in the treated rats. Peroxisome has beta-oxidation enzymes
      distinct from mitochondrial enzymes, and also play an important role in lipid
      metabolism. Peroxisome proliferators have been shown to regulate the expression
      of CYP4A1 and peroxisomal enzymes by the same mechanism in the rat. In the
      present study, we examine the effect of PenCB treatment on peroxisomal enzymes in
      the liver of guinea pigs. As a result, the enzyme activities of hepatic
      peroxisome, e.g. fatty acid oxidizing system, catalase and urate oxidase, had a
      rising tendency by the treatment with PenCB in the animal. The results suggest
      that the regulation of peroxisomal enzymes and CYP4A1 is also associated in
      guinea pigs, and PenCB provides a similar effect of peroxisomal proliferators to
      the animal. The possible toxicity through the peroxisomal alteration was
      discussed.

PMID- 7628802
TI  - [Studies on PCB toxicity involving 2C subfamily cytochrome P450].
AB  - It has been demonstrated that PCB metabolism is mainly catalyzed by 1A and 2B
      subfamily cytochrome P450s, CYP1A1/2 and CYP2B1/2. These studies were conducted
      mostly with hepatic enzymes in rodents. The 1A and 2B subfamily P450 s are
      constitutively expressed little, but markedly induced by xenobiotics such as 3
      methylcholanthrene and phenobarbital in rodents. On the other hand, the recent
      studies showed that cytochrome P450s in human liver are remarkably different from
      isoform of rodents in constitution and enzyme activities. In the present study,
      we first tried to metabolize some PCBs with 2C subfamily cytochrome P450 (CYP2C)
      purified from dog liver microsomes. The data suggested that CYP2C may not be
      involved in PCB metabolism. Since CYP2C is the same most abundant enzyme as 3A
      subfamily P450 in human liver and plays a major role for metabolism of many drugs
      used clinically, and may also play an important role for metabolism of some
      steroid hormones, we further studied the inhibition of CYP2C-catalyzed steroid
      metabolism by typical PCB congeners. CYP2C-mediated steroid metabolism is greatly
      inhibited by 2, 4, 5, 2', 4', 5'-hexachlorbiphenyl, but not by 3, 4, 5, 3', 4'
      pentachlorobiphenyl. On the contrary, 3, 4, 5, 3', 4'-pentachlorobiphenyl
      markedly suppressed CYP2C expression in the dog liver. These results suggest that
      residual PCBs may affect the current situation of steroid hormones in Yusho
      patients, and may cause PCB drug interactions.

PMID- 7628803
TI  - [Tissue retention of hydroxy and methylsulfonyl metabolites of 2, 2', 4, 4'
      tetrachlorobiphenyl in rats].
AB  - Previously, we have identified a large number of methylsulfonyl metabolites in
      tissues of mink treated with Clophen A50. Most of them were found to be derived
      from CBs with a 2, 5-dichlorophenyl or a 2, 3, 6-trichlorophenyl ring. It is
      further necessary to investigate if CBs with a 2, 4-dichlorophenyl ring could be
      biotransformed to the sulfur-containing metabolites in animals. In the present
      study, 2, 2', 4, 4'-tetrachlorobiphenyl (TCB) was administered i.p. to rats, and
      liver, lung, kidney, adipose tissue and blood were analyzed for the unchanged CB
      and its metabolites. Both hydroxy and methylsulfonyl metabolites were detected in
      all tissues analyzed. Major metabolites were identified as 3-OH-2, 2', 4, 4'-TCB,
      5-5-OH-2, 2', 4, 4'-TCB, 5-MeSO(2)-2, 2', 4, 4'-TCB and 6-MeSO(2)-2, 2', 4, 4'
      TCB. Total level of the four metabolites was estimated to be 1.5 micrograms/g wet
      weight in the liver, corresponding to similar level of the unchanged CB. The
      concentration ratios of 3-OH- to 5-OH-TCB and 5-MeSO2- to 6-MeSO(2)-TCB were
      about 2:3 and 2:1, respectively, in liver and kidney. These results indicate that
      CBs with a 2, 4-dichlorophenyl ring can provide both hydroxy and methylsulfonyl
      metabolites that are retainable in tissues of rats.

PMID- 7628804
TI  - [Preliminary studies on the retention of hydroxylated PCDF metabolites in rat
      blood].
AB  - We recently reported that certain hydroxylated PCB (OH-CB) metabolites were
      selectively retained in blood of rats experimentally dosed with PCB (Aroclor
      1254), and also in blood of seals and humans environmentally exposed to PCBs. We
      also showed that metabolism in vivo of polychlorinated dibenzofurans (PCDFs) gave
      rise to a large number of hydroxylated PCDF (OH-CDF) metabolites, excreted in
      faeces, after oral administration to rats of PCDFs mixture (1, 2, 7, 8-tetraCDF
      14%, 2, 3, 7, 8-tetraCDF 35%, 1, 2, 3, 7, 8-pentaCDF 48%). These results suggest
      that OH-CDFs could be present in blood. In the present study, potential retention
      of OH-CDF metabolites in blood (serum) was investigated in a female Wistar rat
      exposed to the PCDFs mixture. Serum was analyzed for the methylated OH-CDFs by
      gas chromatography (GC) and GC-mass spectrometry. Two major metabolites were
      determined in serum 1 day after oral administration. These were identified to be
      3-OH-2, 4, 7, 8-tetraCDF (A) and 3-OH-2, 4, 7, 8, 9-pentaCDF (B) by comparison
      with synthesized reference compounds. 3-OH-2, 4, 7, 8-tetraCDF and 1, 2, 3, 7, 8
      pentaCDF, respectively, via 3, 4(6, 7)-epoxide intermediate and subsequent NIH
      shift of the 3(7)-chlorine to the 4(6)-position. The amounts of 3-OH-2, 4, 7, 8
      tetraCDF and 3-OH-2, 4, 7, 8, 9-pentaCDF in the serum (5.72 g) analyzed accounted
      for 0.018% of 2, 3, 7, 8-tetraCDF and 0.003% of 1, 2, 3, 7, 8-pentaCDF dosed,
      respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7628805
TI  - [Change of PCDF and PCB concentrations in the blood of Yucheng and Yusho patients
      for 25 years].
AB  - The blood samples of 3 Yucheng patients collected 6-7 times from 1980 to 1993 and
      5 Yusho patients collected 6-8 times from 1982 to 1993 were analyzed for
      congeners of polychlorinated dibenzofurans (PCDF) and polychlorinated biphenyls
      (PCB) by high resolution gas chromatography-mass spectrometry and gas
      chromatography-electron capture detection. In the blood of Yucheng patients, the
      high concentrations of 3 PCDF congeners, 2,3',4, 4',5-penta-CB and 5 PCB
      congeners were eliminated at half-lives of 2.4-2.9, 1.7 and 4.1-6.1 years,
      respectively, while in Yusho patients, 14 years after the incident, their half
      lives were converted to longer times as observed 3.2-13.4, 24.0 and 13.7-34.2
      years, respectively. In the same Yucheng and Yusho patients, the half-lives of
      the 5 PCB congeners were about twice longer than those of the 3 PCDF congeners.
      PCBs are more retainable than PCDFs in human blood.

PMID- 7628806
TI  - Effect of 2, 3, 4, 7, 8-pentachlorodibenzofuran and its analogues on induction of
      sister chromatid exchanges in cultured human lymphocytes.
AB  - We have been already contaminated with various chemicals including highly toxic
      organochlorine compounds such as 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD),
      2, 3, 4, 7, 8-pentachlorodibenzofuran (PenCDF) and 3, 4, 5, 3', 4'
      pentachlorobiphenyl (Co-PenCB). In this study, in order to evaluate the
      genotoxicity of the three chemicals, we have examined their effects on the
      induction of sister chromatid exchanges (SCEs), which has been frequently
      utilized as an indicator of biological and genetic damage due to exposure to
      carcinogens or mutagens, in cultured human lymphocytes in the absence or presence
      of 7, 8-benzoflavone (ANF) and the following results were obtained. 1) TCDD,
      PenCDF and Co-PenCB significantly increased the frequency of SCEs with almost the
      same dose-dependent manner in terms of the concentration of TCDD toxic
      equivalent. 2) 8 x 10(-5) MANF significantly enhanced the frequency of SCEs and
      the simultaneous treatment of ANF and either of TCDD, PenCDF or Co-PenCB seemed
      to exert an additive effect as SCEs inducer. 3) TCDD, PenCDF and Co-PenCB were
      considered to be very potent inducers of SCEs, because their 50% effective
      concentration in SCEs enhancement were only 5 to 10 times higher than the level
      of the adipose tissue in healthy Japanese, namely, 70ppt as TCDD. Consequently,
      the respective TCDD toxic equivalency factors of 0.5 and 0.2 for PenCDF and Co
      PenCB seemed to be reasonable so far as the induction of SCEs was employed as an
      indicator of the genotoxic potency.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7628807
TI  - Influence of five methylsulphonyl PCB congeners on frequency of micronucleated
      cells in cultured human lymphocytes by cytokinesis block method.
AB  - The lungs and blood of Yusho patients and healthy Japanese people have already
      been contaminated with methylsulphonyl polychlorinated biphenyls (MSF-PCBs) at
      relatively high concentration. Therefore, we should give due attention to their
      biological and toxicological effects to man. In this study, in order to mainly
      evaluate non-S-dependent genotoxicity of five MSF-PCB congeners, namely, 3-MSF-4,
      5, 3', 4'-tetrachlorobiphenyl (TCB), 3-MSF-4, 5, 2', 3'-TCB, 3-MSF-2, 5, 2', 4',
      5'-pentachlorobiphenyl (PenCB), 4-MSF-2, 5, 2', 3', 4'-PenCB and 4-MSF-2, 5, 2',
      3', 5', 6'-hexachlorobiphenyl (HCB). We have examined their effects on the
      induction of micronucleated cells, which has been frequently used to estimate the
      dose of ionizing radiation and truly radiomimetic, non-S-dependent, clastogens,
      in cultured human lymphocytes in the absence or presence of 2, 3, 4, 7, 8
      pentachlorodibenzofuran (PenCDF), 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD)
      or 3, 4, 5, 3', 4'-pentachlorobiphenyl (Co-PenCB). The following results were
      obtained. 1) 4 x 10(-5) M7, 8-benzoflavone (ANF) significantly enhanced the
      frequency of micronucleated cells and all of the five MSF-PCB congeners failed to
      induce the formation of micronucleated cells at doses of 5.2 to 9.6 ppm, which
      were about 35,000 times higher than the concentrations in the lungs and adipose
      tissue of healthy Japanese people.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7628808
TI  - [In vitro analysis for cellular toxicity of polychlorinated biphenyls(PCBs) and
      2, 3, 4, 7, 8-pentachlorodibenzofuran (PCDF) on HeLa cell proliferation(III)--the
      effect of cytoactivator and antilipemic agents on cell toxicity].
AB  - We investigated the cell toxicity of polychlorinated biphenyls (PCBs) and 2, 3,
      4, 7, 8-pentachlorodibenzofuran (PCDF) as indicators of the optical density
      (280nm) which is total protein in HeLa cells. Furthermore, the reductive action
      of cytoactivator and antilipemic agents on the PCBs and PCDF toxicity were
      evaluated. The quantity of total cellular protein increased to 20% with the
      addition of sodium dextran sulfate (2.5%) at the presence of PCBs, and 25% in the
      case of PCDF. However, the slope of the curve of cell proliferation of HeLa cells
      at the presence of PCBs or PCDF became to overlap with a control group at the
      presence of any other drugs except for sodium dextran sulfate. These results mean
      that PCBs and PCDF cell toxicity were suppressed a little by sodium dextran
      sulfate, but the case of other cytoactivator and antilipemic agents did not.

PMID- 7628809
TI  - [Polychlorinated biphenyls (PCBs) and polychlorinated quaterphenyls (PCQs)
      concentrations in skin surface lipids and blood of patients with Yusho].
AB  - The relationship between Polychlorinated Biphenyls (PCBs), and Polychlorinated
      Quaterphenyls (PCQs) concentrations in the skin surface lipids and blood was
      investigated in twenty two patients with PCB poisoning (Yusho) and 9 control
      subjects were analyzed. The collection of skin surface lipids was performed by
      the method of cotton pad with 70% ethyl alcohol. The alkaline decomposition
      method described as "the official standard analytical methods for the isolation
      of PCBs and PCQs fractions" was used. In the blood of control group, the mean
      value of PCBs concentration was 1.8 ng/g, and that of PCQs concentration was very
      low and undetectable by our analytical method. On the other hand, the PCBs
      concentration in the Yusho group was three times higher than those in the control
      group. The mean value of PCQs concentration was 1.90 ng/g in Yusho group, while
      it was not detectable in the control group. In the skin surface lipids of
      patients with Yusho, the mean value of PCBs concentration was 668.6 ng/g, but was
      256.7 ng/g in the control group. The mean value of PCQs concentration in the skin
      surface lipids of Yusho patients was 35.4 ng/g, although it was not detected in
      the control group. These values of the skin surface lipids in 1993 were decreased
      as compared with those in 1992. PCBs and PCQs levels in the skin surface lipids
      were higher than those in the blood. These findings suggests that cutaneous
      sebaceous system is one of the excretory systems of polyhalogenated chemicals,
      such as PCBs or PCQs, when these chemicals are precipitated in human or
      mammalian.

PMID- 7628810
TI  - [Effects of polychlorinated biphenyls (PCBs) on porphyrin metabolism-
      experimental porphyria induced by large single doses of PCBs].
AB  - The effects of large single doses of PCBs and iron overload on porphyrin
      metabolism were investigated in male C57BL/6 mice. A single intraperitoneal dose
      of Kanechlor-500 (10 mg/mouse) caused urinary uroporphyrin to increase three days
      after injection. This increase was transient without porphyrin accumulation in
      the liver. Iron overload (12.5 mg/mouse) showed a tendency to prolong the action
      of PCBs.

PMID- 7628811
TI  - [Binding of PCB by several types of dietary fiber in vivo and in vitro].
AB  - We investigated the binding of PCB by dietary fiber in vivo and in vitro. Forty
      male rats consisting of four rats a group were housed and rats of each group were
      given a treatment diet containing rice-bran fiber, spinach fiber, burdock fiber,
      cabbage fiber, soybean fiber Japanese-radish fiber, carrot fiber, corn fiber and
      cellulose for five days. The remaining four rats were fed a non-fiber diet as
      controls. The animals were administered with 0.5 ml of the race-bran oil used by
      Yusho patients and kept on the same diets for five days. Fecal excretion of PCB
      in the group fed rice-bran fiber and spinach fiber was significantly (p < 0.01)
      stimulated 6.6 and 4.1 times, respectively, as compared with controls. Dietary
      fiber was suspended in distilled water, and methanolic solution of PCB was added
      to these suspensions. The mixtures were then incubated. After centrifugation, the
      unbound PCB in supernatant was analyzed by gas chromatograph. Rice-bran fiber and
      spinach fiber bount more PCB than any of the other dietary fiber. A significant
      correlation existed between the amounts of binding PCB in vitro and fecal PCB
      output in rats by eight types of dietary fiber (r = 0.986, p < 0.01).

PMID- 7628812
TI  - [Effect of dietary fiber on fecal excretion and liver distribution of PCDF in
      rats].
AB  - Forty male rats (126 g body weight) consisting of four rats a group were housed
      and rats of each group were given a treatment diets containing cellulose, rice
      bran fiber, spinach fiber, burdock fiber, cabbage fiber, soybean fiber, Japanese
      radish fiber, carrot fiber and corn fiber for five days. The remaining four rats
      were fed a non-fiber diet as controls. The animals were orally administered with
      0.5 ml of the rice-bran oil used by Yusho patients and kept on the same diets for
      five days. The rice-bran oil was contaminated with 2, 3, 7, 8
      tetrachlorodibenzofuran (2, 3, 7, 8-T4CDF, 458.7 ng/ml), 2, 3, 4, 7, 8
      pentachlorodibenzofuran (2, 3, 4, 7, 8-P5CDF, 802.4 ng/ml) and 1, 2, 3, 4, 7, 8
      hexachlorodibenzofuran (1, 2, 3, 4, 7, 8-H6CDF, 752.3 ng/ml). PCDF in feces and
      liver were analyzed by high resolution gas chromatography-mass spectrometry. The
      fecal excretion of 2, 3, 7, 8-T4CDF in the group fed rice-bran fiber and spinach
      fiber was significantly (p < 0.01) stimulated 11.3 and 6.8 times, respectively,
      as compared with controls. Moreover, 2, 3, 4, 7, 8-P5CDF and 1, 2, 3, 4, 7, 8
      H6CDF were excreted in stool at the rate of 4.1 and 3.4 times, respectively and
      2.1 and 2.2 times, respectively, as compared with controls. These results suggest
      that administration of dietary fiber is useful for a new approach to therapy of
      Yusho patients.

PMID- 7628813
TI  - Clinical trial of a combination of rice bran fiber and cholestyramine for
      promotion of fecal excretion of retained polychlorinated dibenzofuran and
      polychlorinated biphenyl in Yu-Cheng patients.
AB  - A clinical trial using the combination of rice bran fiber (RBF) and
      cholestyramine (CHO) was carried out on Yu-Cheng patients in 1993-1994. By the
      analysis of blood and stool samples collected from the patients before and after
      (or during in the case of stool), it was verified that the administration of RBF
      and CHO is effective for excretion of polychlorinated biphenyl (PCB) (p < 0.05)
      and polychlorinated dibenzofuran (PCDF), especially 2, 3, 4, 7, 8
      pentachlorodibenzofuran (p < 0.05). However, the degree of effectiveness varied
      upon individual patients from 60 to 160% for 2, 3, 4, 7, 8
      pentachlorodibenzofuran, from 30 to 110% for 1, 2, 3, 4, 7, 8
      hexachlorodibenzofuran and from 50 to 190% for PCB, respectively.

PMID- 7628815
TI  - [Effect of PCBs on insulin sensitivity in rats].
AB  - Insulin sensitivity was assessed by euglycemic insulin clamp method in the rats
      given Kanechlor (KC)-400 for 1 to 12 weeks. As a result, insulin sensitivity was
      depressed increasingly with period of administration of KC-400. Increases in
      total cholesterol, HDL-C, triglyceride, lipid peroxide and T3 in blood plasma
      were also observed in the experimental rats. Voluntary daily activity of rats
      given KC-400, especially in a later half of night-time, had been depressed since
      approximately 9 weeks after start of the experiment. It was concluded that
      depression of insulin sensitivity might be related to not only disturbance of
      glucose and lipid metabolism, but reduced daily activity in conjunction with
      disturbed thyroid function.

PMID- 7628814
TI  - [Levels of PCDDs, PCDFs and coplanar PCBs in the blood and stool of Taiwanese Yu
      Cheng patients].
AB  - Levels of PCDDs, PCDFs and coplanar PCBs were measured in the blood and stool
      obtained from seventeen patients with Yu-Cheng in Taiwan. The average total
      concentrations of PCDDs, PCDFs and coplanar PCBs in the blood collected from Yu
      Cheng patients in January 1993 and August 1994 were 590 and 570 pg Toxic
      Equivalents (TEQs)/g lipid, respectively. The concentrations of PCDDs, PCDFs and
      coplanar PCBs in the blood of patients were 21, 540 and 10 pg TEQs/g fat,
      respectively. On the other hand, the fecal excretion of PCDDs, PCDFs and coplanar
      PCBs were 26, 720 and 15 pg TEQs/day, respectively. The composition of congeners
      in the feces was quite similar to the one in the blood. The half lives were
      estimated as 9.1 and 8.6 years for 2, 3, 4, 7, 8-pentachlorodibenzofuran and 1,
      2, 3, 4, 7, 8-hexachlorodibenzofuran based on fecal excretion, respectively.

PMID- 7628816
TI  - Blood polychlorinated biphenyls and manifestation of symptoms in chronic "Yusho"
      patients.
AB  - The correlation between blood PCB concentration and clinical manifestation of
      symptoms was investigated in 259 chronic "Yusho" patients, using the information
      obtained from the nationwide health examination conducted in 1988, twenty years
      after the outbreak. Concentrations of blood PCBs ranged 0.6-32.0 ppb (mean;
      4.78), and they were categorized into approximate quartile for analysis. For
      general fatigue, odds ratios at 2.7+, 4.1+, and 6.1+ ppb were 2.4, 3.6, and 3.1,
      respectively, with a reference category of < 2.7 ppb (test for trend; p < 0.005).
      For numbness in extremities, the corresponding odds ratios were 2.8, 2.8, and
      2.9(p < 0.005). For comedone, they were 1.4, 1.0, and 4.0 on face (p < 0.025);
      and 3.6, 4.6, and 9.5 on trunk (p < 0.005), respectively. A distinctive increase
      in odds ratio was observed at 2.7 ppb for these two subjective symptoms; and at
      6.1 ppb for skin symptoms. The blood PCB concentrations among patients were
      relatively close to the normal subjects. Therefore, the observed correlations may
      be due to the effects of PCBs with a peculiar pattern in components, PCQs or
      PCDFs, taken and retained in the patients. Association with blood PCBs was also
      suggested for headaches; abnormal breath sounds; and acneiform eruptions in the
      genital region, but were statistically insignificant. None of the eye symptoms
      showed significant association with blood PCBs.

PMID- 7628817
TI  - [An epidemiologic examination on the prevalence of the periodontal diseases and
      oral pigmentation in Yusho patients].
AB  - An epidemiologic examination was carried out to reveal the prevalence of the
      periodontal diseases and oral pigmentation in Yusho patients 26 years after PCB
      exposure. The results obtained were as follows. 1) 158 teeth of the total 284
      examined teeth had the periodontal pockets deeper than 3 mm and the lower left
      first molar showed the highest prevalence of the periodontal pocket among the
      examined six index teeth. There was no definitive difference not only between
      sexes but also between age groups. However, 42 teeth had the periodontal pockets
      deeper than 4 mm. 2) Oral pigmentation was observed in 25 Yusho patients (33.8%).
      Chronological examination revealed that the prevalence of oral pigmentation
      seemed to be higher in the patients below the age of 49 than in those beyond the
      age of 50, but there was no definitive difference between sexes. It was of
      particular interest that the incidence of oral pigmentation appeared to decrease
      with decrease of the teeth present in number.

PMID- 7628818
TI  - Effect of polychlorinated biphenyls and polychlorinated dibenzofurans on
      leukocyte in peripheral blood and bronchoalveolar lavage fluid.
AB  - In order to investigate immunological abnormalities induced by polychlorinated
      biphenyls and polychlorinated dibenzofurans, we have performed bronchoalveolar
      lavage in the rats given polychlorinated biphenyls and polychlorinated
      dibenzofurans. We have administrated 5.0 mg of polychlorinated biphenyls or 0.5
      mg of polychlorinated dibenzofurans to Sprague-Dawley rats intraperitoneally.
      Four weeks after the administration, mild necrosis of bronchiolar Clara cells and
      mild edema associated with chronic inflammatory infiltration in the alveoli were
      seen in both groups. In the peripheral blood, percentage of T-lymphocyte, helper
      T-cell and suppressor T-cell decreased significantly both in polychlorinated
      biphenyls and polychlorinated dibenzofurans given rats. On the other hand, in the
      bronchoalveolar lavage fluid, percentage of T-cell increased only in
      polychlorinated dibenzofurans given rats and percentage of suppressor T-cell
      increased in both groups. O2- release by alveolar macrophage increased
      significantly both when stimulated with wheat germ lectin and with phorbol
      myristate acetate. These results indicate that immunological alternation may be
      different between peripheral blood and respiratory system as one of the target
      organs of these chemicals. Further examination is needed for the analysis of
      immunological abnormalities in the target organs of polychlorinated biphenyls and
      polychlorinated dibenzofurans poisoning.

PMID- 7628819
TI  - [Effects of polychlorinated biphenyls on regeneration of the peripheral nerve in
      rats].
AB  - The effects of polychlorinated biphenyls (PCB) on regeneration of the peripheral
      nerves were investigated in rats. The sciatic nerves were crushed at the mid
      thigh level on the last day of 32 days of oral administration of PCB. The sciatic
      nerves were biopsied from the crushed regions at 1, 2, 4, 8 and 12 weeks after
      crushing. Myelin thickness on the axon diameter was smaller in the PCB
      administered group than in the control group. There was no difference between the
      experimental group and the control group in the density of regenerating fibers
      and distribution of fiber diameters in unmyelinated fibers. After 12 weeks the
      number of large diameter myelinated fiber densities was lower in the experimental
      group than in the control group. These results indicate that PCB may affect the
      remyelination of the regenerating nerve.

PMID- 7628820
TI  - [Laboratory findings in patients with Yusho: 26 year follow-up study].
AB  - To evaluate chronic effect of PCBs on laboratory findings, peripheral blood cells
      and biochemical parameters were studied in 74 patients with Yusho in 1994. Serum
      level of triglyceride was elevated in 21 cases (28.4%) of these patients. Serum
      triglyceride levels showed statistically significant correlation with body mass
      index (Quetelet Index) and blood PCB concentration. We conclude that
      hypertriglyceridemia in patients with Yusho is not frequent and it may be
      associated with both obesity and blood PCB concentration.

PMID- 7628821
TI  - [Dermatological findings in the annual examination of the patients with Yusho in
      1993-1994].
AB  - We reported the grades of severity of skin symptoms and the blood PCB patterns
      and concentrations in Yusho patients who were examined in the annual examinations
      in 1993 and 1994. The skin severity grades and skin severity scores showed the
      same tendency as recorded in the last 15 years. Approximately 20% of the
      patients, however, claimed the tendency of recurrence of skin infections and/or
      infected epidermal cysts, and still approximately 30% of the patients exhibited
      acneiform eruptions. Ten patients recorded with more than 6 points of skin
      severity scoring in these examinations were further investigated their initial
      skin severity grades and blood PCB patterns and concentrations. It was found that
      most of their blood PCB patterns showed the A pattern, and the level of the blood
      PCB in one patient was 55.5 ppb in the initial stage. Five patients out of 10
      patients still have more than 10 ppb of blood PCB concentration. Thus, it is
      concluded that small populations of Yusho patients still have active skin
      symptoms with considerable blood PCB levels even at present.

PMID- 7628822
TI  - Molecular pharmacology of somatostatin receptors.
AB  - Somatostatin was discovered for its ability to inhibit growth hormone (GH)
      secretion. Later, it was found to be widely distributed in other brain regions,
      in which it fulfills a neuromodulatory role, and in several organs of the
      gastrointestinal tract where it can act as a paracrine factor or as a true
      circulating factor. In mammals, two molecules of 14 (somatostatin 14) and 28
      (somatostatin 28) amino acids are the only biologically active members of the
      family. They originate from a single gene which gives rise to a single propeptide
      alternately cleaved in different tissues. In 1992, a major breakthrough in our
      understanding of somatostatin functions was made with the cloning of five
      different receptor genes (sstr1 to sstr5) which belong to the seven transmembrane
      domain receptor family. Their closer relatives are opioid receptors. In first
      approximation, the tissular expression of the sstrs matches quite well with the
      distribution of somatostatin binding sites in the "classical" targets of the
      peptide ie brain, pituitary pancreatic islets and adrenals. The pharmacology of
      GH inhibition is very close to sstr2 binding but other actions of somatostatins
      have not yet been attributed clearly to a single receptor subtype. All clinically
      relevant agonists tested so far (octreotide, lanreotide and vapreotide) are
      selective of sstr2 being less potent on sstr3 and inactive for sstr1 and sstr4.
      Surprisingly, rat sstr5 displays nanomolar affinities for octreotide and
      vapreotide while these agonists are only active at much higher concentrations on
      human sstr5. All five receptors can be more or less efficiently coupled to
      inhibition of adenylate cyclase activity in transfected cell systems.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7628823
TI  - Beta 3-adrenoceptors and airways.
AB  - beta 3-adrenoceptors have been identified in a variety of tissues from humans and
      animals: adipose tissue, gastrointestinal smooth muscle, rat skeletal muscle,
      bovine skeletal muscle, and human and canine heart. In the airways, the
      investigation of the beta 3-adrenoceptors came from studies with a series of
      novel selective agonists. Stimulation of the "atypical" beta-adrenoceptor
      increases the active transport of albumin across the ferret tracheal epithelium
      and the ciliary beat frequency of canine bronchial epithelium. Furthermore, it
      has been demonstrated that beta 3-adrenoceptors agonists selectively inhibited
      nonadrenergic noncholinergic contractions of guinea-pig bronchi induced by
      electrical field stimulation or capsaicin. The presence of functional beta 3
      adrenoceptors in the bronchial smooth muscle is disputed and seems to be species
      related. In isolated canine bronchi, selective agonists induced a relaxation
      whereas they had no or slight effect in isolated human, guinea-pig and sheep
      bronchi. Likewise in man, a fall in airway resistance measured by
      plethysmography, was mediated by beta 2-adrenoceptors, but not beta 3
      adrenoceptors. To conclude, an "atypical" or beta 3-adrenoceptor-mediated
      modulation of bronchomotricity exists, nevertheless strong species specific
      differences have been reported.

PMID- 7628824
TI  - In vitro pharmacological characterization of UP 269-6, a novel nonpeptide
      angiotensin II receptor antagonist.
AB  - f1p4in vitro pharmacology of UP 269-6, a novel nonpeptide angiotensin II
      antagonist, was examined in radioligand binding and functional isolated tissue
      assays. UP 269-6 bound selectively to AT1 receptors as evidenced by the
      inhibition of specific [125I] Sar1, Ile8-AII binding in rat adrenal membranes
      (IC50 = 35.8 nM) and in cultured vascular smooth muscle cells (IC50 = 23.8 nM).
      UP 269-6 displayed a very high selectivity for the AT1 compared to the AT2
      receptor subtype (IC50 > 10,000 nM). UP 269-6 inhibited the AII-induced
      contraction of isolated rabbit aortic strips. The pattern of AII antagonism
      suggested competitive antagonism at low concentrations (10(-10), 3 x 10(-10), 10(
      9) M) of UP 269-6 and insurmountable antagonism at higher concentrations (3 x 10(
      9), 10(-8), 3 x 10(-8) M). Based on the calculated pA2 values, UP 269-6 (9.86 +/-
      0.25) was an angiotensin II receptor antagonist as potent as L-158,809 (9.82 +/-
      0.37) and much more potent than losartan (7.96 +/- 0.38). UP 269-6 was devoid of
      affinity (IC50 > 10,000 nM) for many other receptors, ion channels and uptake
      sites, demonstrating its high specificity for AII receptors. Furthermore, this
      compound did not affect the contractile response to KCl or phenylephrine in
      rabbit aorta and exhibited no effect on angiotensin converting enzyme activity.
      These data demonstrate that UP 269-6 is a highly potent, selective and specific
      AT1 receptor antagonist.

PMID- 7628825
TI  - Release of spermidine from the rat cortex following permanent middle cerebral
      artery occlusion.
AB  - We have studied the effects of middle cerebral artery (MCA) occlusion in rats on
      polyamine efflux in the parietal cortex using the microdialysis technique.
      Dialysis probe implantation itself provoked a delayed, prolonged and vigorous
      release of spermidine and putrescine. Spermidine release returned to stable
      baseline levels within 48 hours. Putrescine release also returned to lower levels
      within this time period but putrescine levels in the dialysate fluctuated
      dramatically in individual animals. Because of the underlying effects of the
      dialysis probe (likely a reflection of traumatic cerebral damage and stimulation
      of polyamine metabolism and release within the immediate vicinity of the dialysis
      probe), MCA occlusion was performed 48 hours after probe implantation. MCA
      occlusion persistently (5/5 animals) resulted in a significant increase in
      cortical spermidine efflux, although the onset, magnitude and duration of this
      increased release was variable. Putrescine efflux was significantly increased in
      2/5 animals with MCA occlusion but the increase in release was similar to the
      spontaneous fluctuations observed in control animals. Spermine was not detectable
      in cortical dialysates of control or MCA occluded groups. Spermidine, but not
      spermine or putrescine is consistently released from the parietal cortex
      following permanent focal ischaemia and may contribute to ischaemic
      neuropathology either through its effects at the N-methyl-D-aspartate (NMDA)
      receptor or via direct, and as yet uncharacterised, neurotoxic effects.

PMID- 7628826
TI  - Blockers of NMDA-operated channels decrease glutamate and aspartate extracellular
      accumulation in striatum during forebrain ischaemia in rats.
AB  - Brain microdialysis was used to study changes in the glutamate and aspartate
      extracellular concentrations in the striatum of conscious rats submitted to 30
      minutes cerebral ischaemia, using the four-vessel occlusion model. Perfusion of
      the N-methyl-D-aspartate (NMDA) receptor channel blockers, dizocilpine (MK-801;
      75 microM) and Mg2+ (2.5 mM), inhibited the ischaemia-induced accumulation of
      glutamate and aspartate. The AMPA/kainate receptor antagonist, 2,3-dihydroxy-6
      nitro-7-sulfamylbenzo (F) quinoxaline (NBQX; 15 microM and 450 microM) had no
      effect on glutamate and aspartate levels during ischaemia. On the other hand,
      omission of Ca2+ from the perfusing solution did not alter the increases in
      glutamate and aspartate induced by ischaemia. These results suggest that the
      glutamate and aspartate accumulation in four-vessel occlusion ischaemia is
      mediated by activation of NMDA receptors in a Ca2+ independent manner.

PMID- 7628827
TI  - Analgesic effect of the direct D2 dopamine receptor agonist RU 24926 and cross
      tolerance with morphine.
AB  - The direct D2 dopamine receptor agonist RU 24926, administered subcutaneously to
      mice, elicited, starting at the dose of 0.125 mg/kg, a dose dependent analgesic
      effect, assessed as the jump latency from a hot plate (55 degrees C). The
      analgesic effect induced by 0.25 mg/kg RU 24926 was dose dependently antagonized
      by the preferential D2 dopamine receptor antagonist haloperidol (ID50 = 15.1 +/-
      3.3 micrograms/kg sc) as well as by the opioid receptor antagonist naloxone (ID50
      = 0.59 +/- 0.17 mg/kg sc). The reversion of RU 24926-induced analgesia by
      naloxone was not accompanied by a reversion of hypothermia. Semi-chronic
      administration of RU 24926 (2.5 mg/kg, sc, 3 times a day for 3 days) completely
      desensitized to the analgesic effect induced by a 0.25 mg/kg test dose of RU
      24926 and partially reduced the analgesic effect of low doses of morphine (0.5,
      1, 1.5 mg/kg). Conversely, semi-chronic administration of morphine (32 mg/kg sc,
      twice daily for 4 days) completely desensitized the analgesic effect induced by a
      2 mg/kg test dose of morphine and partially reduced the analgesic effect of RU
      24926 (0.25, 0.5 and 1 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7628828
TI  - Acute hemodynamic effects of combined inhibition of neutral endopeptidase and
      angiotensin converting enzyme in spontaneously hypertensive rats.
AB  - Neutral endopeptidase inhibitors (NEPI) potentiate the hypotensive effect of
      converting enzyme inhibitors (CEI) in conscious spontaneously hypertensive rats
      (SHR) but the mechanism of this potentiation remains unknown. The present study
      assesses the hemodynamic effects of a CEI (enalaprilat 1 mg/kg; n = 9), a NEPI
      (retrothiorphan 25 mg/kg + 25 mg/kg/h; n = 9) and the combination (CEI+NEPI; n =
      9) versus a control group (n = 9) in anesthetized spontaneously hypertensive
      rats. CEI alone induced a significant hypotensive effect due to a decrease (
      35.1%) in total peripheral resistance (TPR), with no significant increase in
      cardiac output (CO). NEPI alone had a slight hypotensive effect due to a small
      decrease in CO. CEI+NEPI decreased the mean arterial pressure to the same extent
      (-26.7%) as the CEI-induced hypotensive effect, decreased TPR (-44.4%) and
      induced an increase in CO (+38.2%) with an increase in heart rate. In summary,
      NEPI combined with CEI induces large decreases in blood pressure and in TPR which
      do not significantly differ from the CEI-induced effects. It also induces
      increases in heart rate and in cardiac output in anesthetized SHR.

PMID- 7628829
TI  - Effect of Na+ reduction and monensin on ion content and contractile response in
      normoxic and ischaemic reperfused rat hearts.
AB  - The possibility was explored whether the functional properties of Na+/Ca2+
      exchange are altered after ischaemia, thereby contributing to the elevated
      intracellular (i) Ca2+ levels in ischaemic reperfused hearts. The intracellular
      Na+, K+ and Ca2+ contents in rat Langendorff heart preparations were determined
      by atomic absorption spectrometry under normoxic conditions, after ischaemia (30
      min) and after ischaemia (30 min) plus reperfusion (30 min). In addition, the
      influence of modulating the Na+ gradient (Na+o/Na+i) across the sarcolemma was
      studied with respect to cardiac contractility and intracellular ion content. This
      was done by either decreasing extracellular (o) Na+ or by increasing Na+i with
      monensin, both in normoxic and reperfused hearts. Both Na+o reduction and
      monensin led to an increase in contractility and coronary flow, an effect which
      was nearly abolished in reperfused hearts. Under normoxic conditions the
      intracellular ion contents amounted to Na+ = 12.4 +/- 0.4, K+ = 99.0 +/- 3.1 and
      Ca2+ = 0.64 +/- 0.02 mmol/kg cell (means +/- SEM, n = 7). In normoxic hearts,
      lowering Na+o reduced and monensin increased Na+i, thereby both leading to a
      decrease in Na+ gradient; no effect on total Ca2+i content was observed. Na+i
      increased twofold after ischaemia as compared to the normoxic situation, an
      effect which was aggravated (4 fold increase) in reperfused hearts. The opposite
      effects were observed for K+i with a 25% decrease after ischaemia and a 40%
      decrease in reperfused hearts. Only after ischaemia plus reperfusion was Ca2+i
      increased (6 fold).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7628830
TI  - Stress-induced 5-HT1A receptor desensitization: protective effects of Ginkgo
      biloba extract (EGb 761).
AB  - The effects of sub-chronic cold stress on the functioning of hippocampal 5-HT1A
      receptors in old isolated rats and the possible protective effects of Ginkgo
      biloba extract (EGb 761) were investigated. Cold exposure during five days,
      produced a significant reduction of the inhibitory effect of 8-hydroxy-2-(di-n
      propylamino)tetraline (8-OH-DPAT) on forskolin-stimulated adenylyl cyclase
      activity. In contrast, neither the affinity nor the density of hippocampal [3H]8
      OH-DPAT binding sites were affected indicating that the reduced sensitivity of 5
      HT1A receptors induced by stress is probably due to a modification of their
      coupling mechanisms to adenylyl cyclase. The stress-induced desensitization of 5
      HT1A receptors was prevented by the administration of EGb 761 (50 mg/kg per os/14
      days). These results clearly indicate that 5-HT1A receptors are desensitized by
      stress and point out the reduced capacity of old rats to cope with the adverse
      effects of a chronic stressor. EGb 761 appears to restore the age-related
      decreased capacity to adapt to a chronic stressor.

PMID- 7628831
TI  - The effect of LU-49938 (nexopamil) on the activation by serotonin of mesangial
      cells.
AB  - Intraglomerular platelet activation may release vasoactive agents such as
      serotonin (5-hydroxytryptamine, 5-HT) that may affect local hemodynamics and
      promote mesangial proliferation, eventually leading to glomerular sclerosis. The
      main purpose of this study is to analyze whether nexopamil, a verapamil
      derivative, with the property of blocking simultaneously calcium channels and 5
      HT2 receptors, could modify the contractile and mitogenic effects of serotonin on
      cultured rat mesangial cells. Serotonin caused a concentration-dependent increase
      in [3H]thymidine incorporation into DNA, and mesangial cell proliferation. The
      effects of 5-HT on thymidine uptake and cell proliferation were blocked by the
      selective 5-HT2 receptor blocker ketanserin 10(-5) M. Nexopamil abolished in a
      concentration-dependent way the serotonin-induced [3H]thymidine incorporation
      into DNA, and the serotonin-induced increase in number of cells. Using 5-HT 10(
      4) or 10(-5) M, nexopamil had significant effects at concentration above 10(-7)
      M. Serotonin induced a concentration- and time-dependent reduction of planar cell
      surface area. This effect was also completely blocked by ketanserin. Nexopamil
      partially blocked the serotonin-induced mesangial cell contraction, in a dose
      dependent manner. All these data suggest that nexopamil inhibits both 5-HT
      induced mesangial cell contraction and proliferation by blocking 5-HT2 receptors
      and the voltage-operated Ca2+ channels.

PMID- 7628832
TI  - Reduced beta-adrenergic sensitivity in healthy volunteers induced by
      hypoglycemia.
AB  - A single causative mechanism for development of hypoglycemia unawareness in
      insulin-dependent diabetes mellitus (IDDM) is not yet apparent. Reduced
      adrenergic sensitivity may be part of the explanation. This study was carried out
      to investigate the effect of hypoglycemia on beta-adrenergic sensitivity. Ten
      healthy male subjects (age 19-23 years) gave informed consent to take part in the
      study. They were hospitalized overnight at the University Hospital of Tromso,
      Department of Clinical Research, on two occasions. Isoprenaline and metoprolol
      sensitivity tests were performed the morning after hospitalization: once after an
      intravenous (iv) injection of placebo (0.9% NaCl), and once after an iv injection
      of insulin (0.15 IU insulin/kg body weight) to induce hypoglycemia. The dose of
      isoprenaline needed to increase heart rate (HR) by 25 beats per minute (bpm)
      (I25), and the dose of metoprolol (M-12.5) needed to inhibit I25 with 50% or 12.5
      bpm, when injected simultaneously, were used as determinants of isoprenaline and
      metoprolol sensitivity. In this study, there was a significant (p < 0.05)
      increase both in I25 and M-12.5 after hypoglycemia. The dose-response curve of
      isoprenaline/HR was significantly shifted to the right after hypoglycemia. This
      study shows that acute hypoglycemia induces a reduction in beta-adrenergic
      sensitivity, and it supports the hypothesis of reduced beta-adrenergic
      sensitivity as an important pathophysiological mechanism in hypoglycemia
      unawareness in IDDM.

PMID- 7628833
TI  - Ambulatory blood pressure monitoring and cardiovascular function tests in
      multiple system atrophy.
AB  - Cardiovascular tests (CT) of autonomic function and non-invasive ambulatory blood
      pressure (BP) and heart rate (HR) monitoring were performed in 17 patients with
      multiple system atrophy (MSA) (mean age 61 +/- 9 years) and in 12 healthy
      subjects matched for sex and age. CT showed severe autonomic dysfunction with
      orthostatic hypertension (OH) in eight patients with MSA (47%) (Group I). The
      remaining nine out of the 17 patients didn't show BP abnormalities during CT but
      an impaired HR reflex response was found (Group II). BP monitoring showed a
      reversed circadian BP rhythm in Group I with higher night-time than day-time
      values, a blunted circadian BP pattern in Group II and a normal day-night BP
      reduction in controls. Day-night HR reduction was poor in Group II and absent in
      Group I. Post-prandial hypotension was evaluated after a standard meal. In Group
      I systolic/diastolic BP fell within 30 minutes after meal (from 135 +/- 16/89 +/-
      13 to 118 +/- 17/73 +/- 12 mmHg; p < 0.05) and after two hours had not returned
      to basal levels. In Group II a reduction of only systolic BP was found within 45
      minutes after meal and persisted for one hour. OH clinically identifies a
      subgroup of MSA patients with a more severe BP dysregulation characterized by
      severe post-prandial hypotension and reversed circadian BP rhythm. CT and
      ambulatory BP monitoring are useful tools in identifying early stage of
      cardiovascular autonomic impairment.

PMID- 7628834
TI  - Pharmacokinetic and bioavailability of diltiazem sustained-release: influence of
      food and time of administration.
AB  - Diltiazem is a calcium channel blocking agent known to be effective in the
      treatment of angina pectoris, hypertension and supraventricular arrhythmias. To
      improve the conditions of diltiazem administration in the treatment of
      hypertensive patients, a sustained-release formulation (Mono-Tildiem LP 300 mg)
      allowing a single daily oral administration has been developed. The aim of the
      present study was to first evaluate the influence of food intake and second to
      evaluate those of the time of administration on the pharmacokinetic parameters
      and the bioavailability of this sustained-release formulation. The influence of
      these factors was investigated over two different open, randomized, cross-over
      studies in 12 healthy volunteers. Although a significant decrease in Tmax and an
      increase in Cmax occurred when diltiazem sustained-release was administered with
      food intake, AUC0-48, and therefore the fraction absorbed, were not modified
      either by concurrent food intake or by different times of administration. The
      minor modifications of pharmacokinetic parameters of diltiazem sustained release
      observed were unlikely to induce any clinical consequence.

PMID- 7628835
TI  - Endotoxins modify muscle fatigue characteristics.
AB  - To test the hypothesis that endotoxins can directly modify muscle fatigue
      characteristics, in vitro experiments were performed on rat muscles 48 hours
      after injection of lipopolysaccharides (LPS) from Klebsiella pneumoniae.
      Resistance to fatigue was quantified by measuring tension production during
      repetitive electrical stimulation of the isolated epitrochlearis muscle. LPS
      treatment did not significantly modify initial force production whereas
      fatigability of the muscle was increased. This in vitro preparation should be
      used for testing antifatigue drugs.

PMID- 7628836
TI  - Pharmacokinetics of tiopronin after repeated oral administration in rheumatoid
      arthritis.

PMID- 7628837
TI  - Adenosine transformation by human red blood cell membranes.

PMID- 7628839
TI  - The ultimate gift.

PMID- 7628838
TI  - Regulation of beta 3-adrenoceptor expression in white fat cells.
AB  - Catecholamines (adrenaline and noradrenaline) stimulate adipocyte lipolysis via
      three beta-adrenoceptor subtypes beta 1, beta 2 and beta 3. beta 3-adrenoceptor
      mediated lipolysis varies according to the species. Rodent adipocytes exhibit the
      strongest response to beta 3 agonists while human fat cells are poorly
      responsive. The species-related differences can partly be explained by lower beta
      3-adrenoceptor mRNA levels in human adipocytes compared to rat adipocytes. Poor
      coupling efficiency of human adipocyte beta 3-adrenoceptors cannot, however, be
      ruled out. The regulation of beta 3-adrenoceptor gene expression has been studied
      in the adipocytes of the murine cell line 3T3-F442A which express high levels of
      beta 3-adrenoceptors. Insulin and glucocorticoids down-regulate beta 3
      adrenoceptor expression through a transcriptional effect. The impairment of beta
      3-adrenoceptor gene expression in adipocytes of congenitally obese ob/ob mice
      could be related to the higher glucocorticoid plasma levels when compared to lean
      littermates although the direct involvement of glucocorticoids remains to be
      demonstrated. In the rat and the rabbit, the beta 3-adrenergic responsiveness
      varies according to the anatomical location of the fat pad. There is a marked
      decrease in beta 3-adrenergic response in rabbit retroperitoneal fat cells during
      ageing. cAMP modulates the beta 3-adrenergic response in white adipocytes at
      different levels. Human beta 3-adrenoceptor expression seems to be up-regulated
      by cAMP through an interaction with the promoter of the gene. It has been shown
      in cells transfected with cDNAs for the different beta-adrenoceptors that the
      beta 3-adrenoceptor is less prone to desensitization than the beta 1 and beta 2
      subtypes. This observation is in agreement with the absence of desensitization of
      the beta 3-adrenoceptor response in isolated rat fat cells. Continuous infusion
      of noradrenaline for six days into hamsters does not lead to an alteration of the
      beta-adrenergic response. A similar treatment undertaken in the guinea pig, a
      species, unlike the hamster, devoid of beta 3-adrenoceptor responsiveness,
      promoted strong desensitization of the beta-adrenergic response through down
      regulation of beta 1- and beta 2-adrenoceptors. From these observations, it could
      be hypothesized that the beta 3-adrenoceptor, that shows a low affinity for
      catecholamines, is the "emergency" beta-adrenoceptor which is essential under
      conditions of strong and sustained sympathetic nervous system activation.

PMID- 7628840
TI  - Building on a tradition of ethical consideration of the dead.
AB  - Medical culture espouses patient interaction based on detached concern, where
      emotional attachment to patients is attenuated to preserve objectivity. The body
      is viewed as nonliving matter in motion. Alternatively, the cadaver may be
      considered a gift. To receive so awesome a gift is an extraordinary privilege;
      acknowledgment of this gift affirms our interconnectedness with our community and
      offers a way to provide for its betterment. Gift exchange establishes a
      relationship between donor and recipient, and the absence of an assigned worth
      leaves open the cycle of giving and receiving for future exchanges. Inherent
      within undertaking a dissection lies an obligation that the gift not be wasted.
      Donating one's body for dissection meets the criteria for the highest levels of
      charity as set forth by the 12th-century philosopher, physician, and rabbinic
      scholar Moses Maimonides. Preserving the anonymity of cadavers protects students
      as well by enabling them to dissect in an environment that respects the sensitive
      and difficult nature of the work. Maimonides provides support for formalizing the
      anonymous relationship between student and cadaver. The anonymous nature of the
      gift provides enormous latitude for using the skills thus gained to serve one's
      patients and to benefit the common good.

PMID- 7628841
TI  - Chondroid lipoma: an ultrastructural and immunohistochemical analysis with
      further observations regarding its differentiation.
AB  - Chondroid lipoma was recently described as a unique, benign, pseudosarcomatous
      lipomatous tumor with chondroid features, often simulating liposarcoma and myxoid
      chondrosarcoma. An extended histochemical and immunohistochemical analysis of 13
      cases, including the proliferation markers, proliferating cell nuclear antigen
      (PCNA) and Ki67, as well as ultrastructural studies of eight cases were performed
      with the intent of further elucidating its differentiation. Staining with
      toluidine blue and alcian blue at controlled pHs indicated the presence of
      chondroitin sulfates within the myxohyaline matrix. Immunohistochemically, all
      tumors were positive for vimentin and S100 protein. Focal immunoreactivity for
      cytokeratins was seen in 3 of 13 cases; one of these also had intracytoplasmic
      tonofilament bundles ultrastructurally. Scattered tumor cells stained for CD68
      antigen with KP1 in 6 of 13 cases. None of the tumors stained for epithelial
      membrane antigen (EMA) or alpha-smooth muscle actin. Collagen IV immunostains
      showed a network of fibrils encircling individual tumor cells in 10 of 13 cases.
      Intracytoplasmic staining for laminin was found in 9 of 13 cases.
      Ultrastructurally there was a spectrum of differentiation, ranging from primitive
      cells sharing features of prelipoblasts and chondroblasts, to lipoblasts and
      preadipocytes, to mature adipocytes. A striking ultrastructural feature in 5 of 8
      cases was the presence of knob-like protrusions of the cell membrane, which
      contained granular, amorphous, and fibrillar material that appeared to be
      extruded into the adjacent matrix. The myxohyaline matrix had ultrastructural
      features of cartilage. Numerous mitochondria and lysosomes were absent,
      indicating that chondroid lipoma is neither a hibernomatous lesion nor a
      lipogranuloma. Ki67 immunoreactivity was typically very low and detected only in
      the more primitive cell population. The findings in this analysis indicate that
      chondroid lipoma is a pseudosarcomatous lipogenic neoplasm with a unique cell
      population possessing predominantly features of embryonal fat and, to a lesser
      extent, embryonal cartilage.

PMID- 7628842
TI  - Spectrum of vascular pathology affecting patients with the antiphospholipid
      syndrome.
AB  - A thrombotic microangiopathy that is identified in patients with the
      antiphospholipid syndrome (APS) represents only a part of the vascular pathology
      that can be associated with antiphospholipid antibodies (aPL). Tissues from two
      autopsies, four renal biopsies, two skin biopsies, and one amputated leg were
      obtained from six patients who met criteria for the diagnosis of APS. Three
      patients had systemic lupus erythematosus (SLE), one had lupus-like disease, and
      two had a primary APS. Five of the patients were hypertensive. Arteries of three
      patients disclosed fibrin thrombi along with widespread obstruction by
      recanalized intimal connective tissue. Small renal, leptomeningeal, and pulmonary
      arteries showed concentric cellular and fibrous intimal hyperplasia
      indistinguishable from hypertensive vascular disease. Glomerular capillary and
      afferent arteriolar thrombi were found in renal biopsies from two SLE patients.
      One of these SLE patients required a leg amputation in which the popliteal artery
      demonstrated thrombosis, intimal hyperplasia, and acute inflammation. The
      findings support clinical and experimental data that indicate aPLs cause
      thrombosis but suggest diversity in the pathogenetic mechanisms aPLs are capable
      of promoting. Inflammation seems to be rare and to accompany thrombosis. Intimal
      hyperplasia is particularly common. Its involvement of renal arteries may
      contribute to hypertension that develops in some APS patients.

PMID- 7628843
TI  - Proliferative markers in gastric carcinoma and organoid differentiation.
AB  - The present study was undertaken to elucidate the relationship between the
      distribution of potentially proliferative tumor cells and the organoid
      differentiation of tumor cells in gastric carcinomas. One hundred four specimens
      of surgically removed human gastric carcinomas, including 68 and 36 specimens of
      early and advanced carcinomas, respectively, were studied by using a battery of
      histochemical techniques. Serial 3-microns thick paraffin sections were stained
      by galactose oxidase-cold thionine Schiff-paradoxical concanavalin A staining
      (GOCTS-PCS), or were immunostained for pepsinogen types I and II, lysozyme, and
      proliferating cell nuclear antigen (PCNA). In addition, to identify proliferative
      tumor cells parts of fresh carcinoma tissues were incubated in a solution
      containing bromodeoxyuridine (BrdU), embedded in paraffin, and immunostained for
      BrdU. The results indicated that in intramucosal carcinoma tissues showing
      organoid differentiation the proliferative tumor cells were located predominantly
      between the covering epithelial cell type tumor cells and the glandular mucous
      cell type tumor cells, and the disturbance in the distribution of proliferative
      cells coincided with the submucosal invasion.

PMID- 7628844
TI  - Sialyl-Lewis(x) and related carbohydrate antigens in the prostate.
AB  - Alteration of cell surface carbohydrate antigens during malignant transformation
      is a well-known phenomenon observed in various tumors. In prostatic carcinoma,
      nearly total deletion of normally occurring ABO and type I-based Lewis antigens,
      Le(a) and Leb, has been observed in several studies. We studied expression of the
      closely related type II antigens Le(x), Le(y), and sialyl-Lewis(x) (SLe(x)) using
      monoclonal antibodies. Thirty formalin-fixed specimens obtained from radical
      prostatectomy, containing prostatic carcinoma as well as benign tissue, were
      evaluated by immunohistochemistry. In both cancer and benign tissue, Le(x)
      expression was minimal or absent. In benign tissue, Le(y) was expressed in ducts
      and in the basal layer of glandular epithelium. In tumor tissue, Le(y) expression
      was greatly increased and extensive staining was observed in 26 of 30 cases. The
      SLe(x) expression in benign tissue was observed only in larger ducts, never in
      glandular secretory epithelial cells. In carcinoma, rare cells positive for
      SLe(x) were present in 8 of 30 cases, and stronger expression with focal to
      patchy distribution was observed in 14 of 30 cases. The results suggest an
      alteration in glycosyl transferase activity in prostatic carcinoma, with
      preserved or increased activity of enzymes responsible for the synthesis of the
      type II core sequence. This sequence is further glycosylated and expressed as the
      difucosylated compound Le(y) or the monofucosyl, monosialyl compound SLe(x). For
      prostate, Le(y) and SLe(x) are the only blood group-related antigens known to be
      minimal or absent in benign secretory epithelial cells that are more highly
      expressed in malignant tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7628845
TI  - Typical and atypical bronchopulmonary carcinoid tumors: a clinicopathologic and
      KI-67-labeling study.
AB  - Expression of a proliferating antigen by KI-67 immunohistochemistry was analyzed
      with a SAMBA 2005 computer-assisted image processor (Traitement de l'Information
      for des Techniques Nouvelles, Grenoble, France) in 47 surgically resected
      bronchopulmonary carcinoids embedded in paraffin. The clinicopathologic
      characteristics and KI-67 labeling, expressed in percentage of stained nuclear
      surface relative to the total nuclear surface, of 31 typical carcinoids and 16
      atypical carcinoids were compared and assessed with respect to patient survival.
      The proliferation status was significantly higher in histologically atypical than
      in typical carcinoids. Moreover, using a 4% cutoff, we observed a significant
      difference for the 4-year overall survival rate. Semiquantitative analysis of the
      proliferation index by KI-67 immunostaining seemed to be an effective means of
      identifying high risk subsets among patients with histologically atypical
      carcinoids and for whom adjuvant chemotherapy could be proposed.

PMID- 7628846
TI  - Expression of pancreatic trypsinogen/trypsin and cathepsin B in human
      cholangiocarcinomas and hepatocellular carcinomas.
AB  - We evaluated in situ expression of pancreatic trypsinogen (PT) and cathepsin B
      (CB) in 10 normal livers, 37 cholangiocarcinomas (CCs), and 36 hepatocellular
      carcinomas (HCCs). In normal livers, PT was expressed in intrahepatic large bile
      ducts, septal bile ducts, and peribiliary glands, and CB was present in
      hepatocytes and all epithelial cells of the intrahepatic biliary system. In CCs,
      PT was present in 26 (70%), of which 24 expressed PT both in CC cells and the CC
      stroma, and the remaining two showed PT only in CC cells. The ratio of PT
      positive cases was high in well-differentiated CCs, moderate in moderately
      differentiated CCs, and low in poorly differentiated CCs. PT in the CC stroma was
      present in continuity with PT-positive CC cells, suggesting that PT was secreted
      from CC cells. The CC stroma positive for PT frequently showed destructive
      features. CB was present in 32 CCs (86%) and located in both CC cells and the CC
      stroma. All PT-positive CCs simultaneously expressed CB, suggesting a close
      association of PT and CB. In HCCs, in contrast, PT was not present in any cases.
      CB was present in 33 HCCs (92%) and located in both HCC cells and the HCC stroma.
      In positive specimens, PT immunoreactivity was finely granular in the cytoplasm,
      whereas CB immunoreactivity was diffuse in the entire cytoplasm. These data
      suggest that after malignant transformation CCs and HCCs continue to express PT
      and CB, and CB, respectively. It seems possible that PT secreted from CC cells is
      converted into trypsin by CB, and that trypsin and CB play a role in CC invasion
      by degrading extracellular matrix proteins.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7628847
TI  - Ploidy analysis by flow cytometry and fluorescence in situ hybridization in
      hydropic placentas and gestational trophoblastic disease.
AB  - Placentas with hydropic change may be hydropic degeneration (HD) or gestational
      trophoblastic disease (GTD), partial (PM) or complete (CM) hydatidiform mole. The
      separation of HD from PM and PM from CM by histological findings may be
      problematic in some cases and can be clarified with ploidy analysis. Fluorescence
      in situ hybridization (FISH) using a probe to chromosome 7 (D7Z1) was applied to
      tissue cut from paraffin blocks from 10 histologically representative cases each
      of HD, PM, and CM on which ploidy had been previously confirmed by flow cytometry
      from paraffin embedded tissue. Villous stromal cells and nonproliferative
      trophoblast were examined for number of signals/cell and percentage of
      cells/placenta with three hybridization signals. The mean number of hybridization
      signals/cell was HD 1.14; PM 1.79; and CM 1.17, with statistical significance
      between HD and PM (P < .0001), and PM and CM (P < .0001). The mean percentage of
      cells/placenta with three hybridization signals was HD 1.10%, PM 23.1%, and CM
      2.11%, with statistical significance between HD and PM (P < .0001), and PM and CM
      (P < .0001). In addition, there was no overlap in the mean percentage of cells
      with three hybridization signals between HD and PM, and PM and CM. Chromosome 2
      probe (D2Z1) was applied to tissues that had three chromosome 7 signals to
      exclude trisomy, and in all cases three signals were present confirming triploidy
      in PM. FISH can identify diploid and triploid hydropic placentas in paraffin
      embedded tissue to assist in differentiating HD from PM, and PM from CM.

PMID- 7628848
TI  - Incidence of hydatidiform mole in a Tokyo hospital: a 5-year (1989 to 1993)
      prospective, morphological, and flow cytometric study.
AB  - This prospective study reports the incidence of hydatidiform mole (HM) in a
      population of 13,510 pregnancies in a Tokyo hospital over a 5-year period between
      1989 and 1993. During this period all "products of conception" from first- and
      second-trimester abortions were histologically reviewed, and 76 hydropic
      placentas were retrieved and analyzed by flow cytometry (FCM). Of 23 specimens
      originally diagnosed as complete hydatidiform mole (CM), 21 were diploid, and two
      were aneuploid (nontriploid/tetraploid). Of 22 partial hydatidiform moles (PMs),
      20 were triploid, and two were diploid. Of 31 hydropic abortions (HAs), 20 were
      diploid, nine were triploid, one was tetraploid, and one was aneuploid. As to the
      correlation between morphology and data of FCM, two PMs were reclassified as HA,
      and eight HAs as PM, giving a ratio of 1 CM to 1.22 PM (23:28 cases). The
      incidence of HM was 1:265 pregnancies, (CM, 1:587; PM, 1:483). Only one case
      (3.6%) of PM was suspected clinically. One specimen of persistent disease
      occurred following a diploid CM. In our retrospective histological and FCM study
      in which 172 cases diagnosed as HM were retrieved from surgical pathology files
      between 1981 and 1991, there were 129 CMs and 43 PMs (CMs:PMs = 3:1). These
      findings indicate that PM is a common but underdiagnosed condition. Almost all
      studies in the literature may have severely underreported the incidence of PM. It
      is suggested that during routine delivery and pathology examination only the most
      florid PMs are recognized, whereas most with subtler changes go
      undiagnosed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7628849
TI  - Pancreatic disorders in pediatric acquired immune deficiency syndrome.
AB  - Acute pancreatitis, reported in 17% of pediatric patients with acquired immune
      deficiency syndrome (AIDS), is said to have a poor prognosis. We describe the
      pancreatic changes observed at autopsy from 71 children with human
      immunodeficiency virus (HIV) infection and document their nature, extent, and
      clinical relevance. The median age at autopsy of the children was 17 months
      (range, 2 months to 19 years); 38 were boys and 33 were girls. Parental
      intravenous drug use was the most frequent risk factor for AIDS, followed by
      blood transfusions. Respiratory failure and sepsis constituted the predominant
      causes of death. Nonspecific changes, such as edema, inflammation, fibrosis,
      inspissated material in acini and ducts, and enlarged Langerhans' islet
      predominated. Acute and chronic pancreatitis were mild except in one instance of
      a fatal acute probably dideoxyinosine-associated pancreatitis. Pancreatic
      involvement by opportunistic infections, such as cytomegalovirus (CMV),
      Mycobacterium avium intracellulare (MAI), and Candida, was focal and rare despite
      the high prevalence of these infections at autopsy. Focal lymphoplasmacytic
      infiltration and vascular calcifications were also observed. We conclude that
      pancreatic changes were frequently noted at autopsy in children with AIDS. They
      were usually mild, reflected systemic disease states, and were usually not life
      threatening. The incidence of opportunistic infections of the pancreas was low.

PMID- 7628850
TI  - Giant cell tumor of tendon sheath and pigmented villonodular synovitis:
      immunophenotype suggests a synovial cell origin.
AB  - Giant cell tumor of tendon sheath (GCTS) and pigmented villonodular synovitis
      (PVNS) are common synovial "tumors." Their immunohistochemical profile, however,
      has not been well characterized, and uncertainty exists regarding their
      histogenesis and relationship to fibroma of tendon sheath. In an effort to
      clarify these uncertainties and to better define the immunohistochemical profile
      of GCTS/PVNS, we examined formalin fixed tissue from 35 specimens of GCTS, 12
      specimens of PVNS, and three cases of reactive synovitis using avidin biotin
      complex (ABC) and streptavidin immunohistochemical methods. Antibodies to
      vimentin, CD68, HAM56, cytokeratins, EMA, S100, HMB45, leukocyte common antigen,
      CD34, desmin, and smooth muscle actin were used in the study. The proliferating
      mononuclear cells and surface synovial cells in GCTS/PVNS and reactive synovitis
      stained positively for CD68, HAM56, and vimentin only. Multinucleated cells
      stained for CD68, vimentin, and leukocyte common antigen. All other stains were
      negative. Our results suggest that GCTS/PVNS are tumors of synovial cell origin,
      and do not support an association between GCTS and fibroma of tendon sheath.

PMID- 7628851
TI  - Use of monoclonal antibody 1H1, anticortactin, to distinguish normal and
      neoplastic smooth muscle cells: comparison with anti-alpha-smooth muscle actin
      and antimuscle-specific actin.
AB  - In preliminary experiments, we found that 1H1, a monoclonal antibody directed
      against the v-src substrate cortactin, reacts with smooth muscle, myoepithelium,
      myofibroblasts, and macrophages in formaldehyde-fixed human tissues. To evaluate
      the use of this antibody as a diagnostic reagent, we tested the
      immunohistochemical distribution of cortactin in 61 mesenchymal neoplasms, 11
      neuroectodermal neoplasms, and eight embryonal epithelial neoplasms. The results
      were compared with those obtained using antibodies against alpha-smooth muscle
      actin and muscle-specific actin on a similar set of tissues. With the exception
      of positive staining in rhabdomyosarcoma, in this series only tumors with smooth
      muscle differentiation appeared to contain cortactin (16 of 19 leiomyosarcomas,
      one infantile fibrosarcoma, one malignant fibrous histiocytoma). Immunoelectron
      microscopy localized cortactin to the actin-associated dense bodies of the
      microfilament network. We conclude that cortactin may be a useful adjunct to
      alpha-smooth muscle actin and muscle-specific actin as a marker for the study and
      diagnosis of smooth muscle neoplasms and related lesions.

PMID- 7628852
TI  - Pathology of the umbilical cord in congenital syphilis: analysis of 25 specimens
      using histochemistry and immunofluorescent antibody to Treponema pallidum.
AB  - Identification of Treponema pallidum in the placenta is important for diagnosis
      of congenital syphilis; however, spirochetes are difficult to observe in
      chorionic villi. To determine the sensitivity of umbilical cord examination for T
      pallidum, and the association of spirochetes with cord pathology, placentas were
      prospectively obtained from 25 women with untreated syphilis. The most common
      finding using hematoxylin-eosin staining was a normal-appearing umbilical cord
      (48%); necrotizing funisitis was the most frequent pathological lesion (36%).
      Spirochetes were detected using silver and immunofluorescent staining in 89% of
      cords, including 92% of histologically normal and 84% of abnormal cords. Three
      specimens showed subamnionic aggregates of spirochetes, consistent with amniotic
      fluid infection. Necrotizing funisitis was strongly associated with umbilical
      artery infection by spirochetes (P = .008). There was a 100% correlation between
      results of silver and immunofluorescent staining. The umbilical cord is a
      sensitive site for morphological confirmation of T pallidum; it is significant
      for the pathologist that spirochetes may often be detected in the absence of
      overt tissue inflammation or necrosis.

PMID- 7628853
TI  - Computer-derived nuclear features distinguish malignant from benign breast
      cytology.
AB  - This article describes the use of computer-based analytical techniques to define
      nuclear size, shape, and texture features. These features are then used to
      distinguish between benign and malignant breast cytology. The benign and
      malignant cell samples used in this study were obtained by fine needle aspiration
      (FNA) from a consecutive series of 569 patients: 212 with cancer and 357 with
      fibrocystic breast masses. Regions of FNA preparations to be analyzed were
      converted by a video camera to computer files that were displayed on a computer
      monitor. Nuclei to be analyzed were roughly outlined by an operator using a
      mouse. Next, the computer generated a "snake" that precisely enclosed each
      designated nucleus. The computer calculated 10 features for each nucleus. The
      ability to correctly classify samples as benign or malignant on the basis of
      these features was determined by inductive machine learning and logistic
      regression. Cross-validation was used to test the validity of the predicted
      diagnosis. The logistic regression cross validated classification accuracy was
      96.2% and the inductive machine learning cross-validated classification accuracy
      was 97.5%. Our computerized system provides a probability that a sample is
      malignant. Should this probability fall between 30% and 70%, the sample is
      considered "suspicious," in the same way a visually graded FNA may be termed
      suspicious. All of the 128 consecutive cases obtained since the introduction of
      this system were correctly diagnosed, but nine benign aspirates fell into the
      suspicious category.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7628854
TI  - Immunohistochemical localization of parathyroid hormone-related protein in
      prostatic intraepithelial neoplasia.
AB  - Parathyroid hormone-related protein (PTHrP) is a regulatory protein hormone that
      has been associated with normal fetal growth and differentiation as well as fetal
      calcium regulation. Parathyroid hormone-related protein has been implicated in a
      variety of carcinomas as a major factor in the development of humoral
      hypercalcemia of malignancy and may also play a role as an autocrine growth
      factor. In a previous immunohistochemical study we found that all prostatic
      adenocarcinomas (CAP) express PTHrP. In the current study, we evaluated PTHrP in
      prostate intraepithelial neoplasia (PIN) in radical prostatectomy specimens. A
      validated mouse monoclonal antibody, 9H7, raised against fragment 109-141 of the
      carboxy-terminus of PTHrP was used for immunostaining. The results generally
      showed negative to weak staining of normal and hyperplastic tissue and strong
      staining in PIN. The staining intensity was further evaluated by computer based
      image analysis. The relative optical density in PIN (9.24 +/- 9.05) was
      significantly (P = .008) higher than that in normal gland (.00 +/- 3.6). These
      findings suggest that PTHrP may be involved in the pathogenesis of prostatic
      dysplasia, and its immunohistochemical evaluation may have diagnostic use in the
      evaluation of PIN.

PMID- 7628855
TI  - Plasmacytoid myoepithelioma of the laryngeal region: a case report.
AB  - The first case of plasmacytoid myoepithelioma of the laryngeal region is
      presented. The tumor showed immunoreactivity for the S-100 protein, low molecular
      weight cytokeratin, and vimentin. Staining was negative with muscular actin and
      glial fibrillar acid protein. By electron microscopy the tumor cells showed
      abundant microfibrillar material, elongated densities resembling smooth muscle
      dense bodies, pinocytic vesicles, and replicated basal lamina. The myoepithelial
      nature of plasmacytoid tumors of the salivary gland has been questioned.

PMID- 7628856
TI  - Intracranial teratoma with multiple fetuses: pre- and post-natal appearance.
AB  - An intracranial teratoma in which six distinct dysmorphic fetuses were included
      was studied at autopsy. Karyotopic studies showed a normal chromosomal number in
      the child and the same karyotype in the three tumoral parts were examined. This
      is the second tumor of this type reported.

PMID- 7628857
TI  - Intraprostatic ganglia.

PMID- 7628858
TI  - p53 and JC virus infection in progressive multifocal leukoencephalopathy.

PMID- 7628859
TI  - Auranofin and its combination with LTB4 influences ATP level and migration of
      human polymorphonuclear cells in vitro.
AB  - Auranofin (AF), an orally administered antirheumatic drug, reduces the ATP level
      of PMN cells in vitro in a dose-dependent manner and provokes various effects on
      PMN migration. Under the experimental conditions, AF in concentrations between
      10(-8) M and 10(-3) M produced a statistically significant (P < 0.05) dose
      related reduction in ATP level, which ranged from 89% of the control value with
      10(-8) M AF to 46.8% of the control with 10(-3) M AF. On the other hand, the
      combination of AF and the chemoattractant LTB4 (1 ng/ml) shows agonistic effects
      on the intracellular ATP level. AF at 10(-5) M significantly increases the ATP
      (33%; P < 0.03). In general migration of PMN cells is stimulated by 10(-7) M AF
      [chemotactic index (CI) = 1.26], but inhibited by 10(-5) M (CI = 0.65), 10(-4) M
      (CI = 0.09) and 10(-3) M AF (CI = 0.01). These effects were statistically
      significant at P < 0.05. In the presence of LTB4 (1 ng/ml), which resulted in an
      average CI of 2.9, AF also inhibits the chemotactic effect of the
      chemoattractant, with the CI being significantly reduced at 10(-6) M AF (CI =
      2.3) and 10(-4) M AF (CI = 0.05). In the latter case the effect was also
      confirmed by the leading-front technique. AF at 10(-6) M is a level that could be
      reached in the blood after continuous therapy regimens, and these results are
      therefore of practical interest. They expand our knowledge of the effects of AF
      on PMN cells, whereby reducing effects on intracellular ATP were observed with AF
      alone and stimulating effects in combination with LTB4. With low AF
      concentrations, the reduction of the ATP level is only a part of its action that
      seems to be independent of its effect on cell migration and chemotaxis.

PMID- 7628860
TI  - Aspirin-induced, neutrophil-mediated injury to vascular endothelium.
AB  - Previous studies indicate that aspirin can promote neutrophil (PMN) adhesion to
      endothelial cells and neutrophil-mediated endothelial cell detachment. The
      objectives of the present study were to determine whether PMN adhesion is a
      prerequisite for aspirin-induced, PMN-mediated endothelial cell detachment and
      whether neutrophil-derived oxidants and/or proteases are responsible for the cell
      detachment. Human PMNs were added to confluent monolayers of human umbilical vein
      endothelial cells (HUVEC) and coincubated with or without aspirin at a clinically
      relevant concentration (300 micrograms/ml). Aspirin-activated PMNs induced
      endothelial cell detachment, but not cell lysis. Endothelial cell detachment was
      always preceded by retraction of endothelial cells within the monolayer. The
      aspirin-induced, neutrophil-mediated cell detachment was prevented by a
      monoclonal antibody directed against CD11/CD18 adhesion integrins on PMNs.
      Elastase inhibitors, but not superoxide dismutase or catalase, prevented both
      endothelial cell retraction and detachment. If aspirin-activated neutrophils were
      allowed to migrate across the monolayers, endothelial cell retraction or
      detachment did not occur. These studies indicate that aspirin-induced, PMN
      mediated endothelial cell retraction and detachment requires PMN adhesion to the
      target cells and is due to neutrophil-derived elastase. Endothelial cell
      retraction, induced by activated neutrophils, may represent an exaggeration of a
      normal physiologic event, i.e., neutrophil emigration.

PMID- 7628861
TI  - Identification and characterization of rhesus macaque interleukin-8.
AB  - To establish a direct link between IL-8 and inflammation in vivo, we first
      isolated the gene encoding rhesus macaque IL-8. The open reading frame directs
      the translation of a 101 amino acid (aa) precursor, which is 94% identical to
      human IL-8. Rhesus IL-8 was expressed in bacteria and purified to homogeneity
      with ion-exchange chromatography. Pure rhesus IL-8 was biologically active as
      measured by its ability to bind specifically to either rhesus (Kd = 0.5 nM) or
      human (Kd = 2 nM) IL-8 receptors and to promote in vitro chemotaxis of rhesus
      (EC50 = 2 nM) or human neutrophils (EC50 = 4 nM). Moreover, a mouse monoclonal
      antibody, DM/C7, which neutralizes human IL-8 activity, also recognized and
      neutralized (IC50 = 0.5-3.0 microgram/ml) rhesus IL-8 in vitro. Systemic
      administration of DM/C7 completely inhibited the dermal inflammation of rhesus
      ears induced by the external application of phorbol myristoyl acetate. These
      observations reveal that rhesus IL-8 is structurally and functionally similar to
      human IL-8 and suggests that IL-8 plays a prominent role in a primate model of
      inflammation.

PMID- 7628862
TI  - Dermal inflammation in primates, mice, and guinea pigs: attenuation by second
      generation leukotriene B4 receptor antagonist, SC-53228.
AB  - Granulocyte infiltration is a prominent feature of human psoriasis. Psoriatic
      lesional skin contains abnormally high amounts of immunoreactive leukotriene B4
      (LTB4), a potent granulocyte chemotaxin in vivo and in vitro. SC-53228 [(+)-(S)-7
      (3-}2-(cyclopropylmethyl)-3-methoxy-4- [(methylamino)carbonyl]phenoxy}propoxy}
      3,4-dihydro-8-propyl-2H-1- benzopyran-2-propanoic acid], a second-generation LTB4
      receptor antagonist, was tested topically and orally in phorbol ester-induced
      dermal inflammation in three species. Skin inflammation was induced by topical
      application of phorbol-12-myristate-13-acetate-(PMA/TPA) and assessed by ear
      thickness, levels of the neutrophil marker enzyme myeloperoxidase (MPO) and
      histological examination. In mice, SC-53228 inhibited inflammation with a topical
      ED50 value of 200 +/- 18 micrograms. When applied to guinea pigs, SC-53228 (100
      micrograms) inhibited the MPO increase by 86%, while 1000 micrograms abrogated
      inflammation in rhesus macaques with no plasma accumulation of the drug. A 1% gel
      formulation was also efficacious in guinea pig PMA-induced epidermal
      inflammation. Furthermore, single oral dose administration to mice was
      efficacious (ED50 < 2.5 mg/kg) as was multidose administration to rhesus
      macaques. PMA-induced skin inflammation possesses some of the attributes of human
      psoriasis and an agent such as SC-53228 may have utility in the medical
      management of this condition.

PMID- 7628863
TI  - Antiinflammatory effects of NADPH oxidase inhibitors.
AB  - Proinflammatory cytokines prime the membrane-bound NADPH oxidase of neutrophils
      and monocytes of mice suffering from experimental arthritis so as to attain an
      activated state, which, upon a second stimulus, releases 6-fold increased levels
      of reactive oxygen species (ROS) than do unprimed phagocytes. Enhanced NADPH
      oxidase activity deregulates ROS-dependent signal transduction pathways of
      inflammation, which play a crucial role in the pathogenesis of arthritis. The
      antiarthritic reactivity of two inhibitors of NADPH oxidase, diphenylene
      iodoniumchloride (DPI) and staurosporine, was tested in male DBA/1 x B10A(4R)
      hybrid mice suffering from potassium peroxochromate arthritis. Daily doses of 2.8
      mumol/kg of DPI or 30 nmol/kg of staurosporine sufficed to inhibit the arthritis
      by 50%. A complete inhibition was obtained with 10 mumol/kg of DPI, and 100
      nmol/kg of staurosporine suppressed the arthritis by 85%. The onset, progression,
      and remission of arthritis correlated to both the activity of phagocytic NADPH
      oxidase (r = 0.750) and to overt disease symptoms as judged by the arthritis
      index. Our data support the hypothesis that oxidative stress plays a pivotal role
      in the pathology of arthritis, which can be therapeutically targeted by NADPH
      oxidase inhibitors.

PMID- 7628865
TI  - Modulation of inflammatory arthritis by inhibition of poly(ADP ribose)
      polymerase.
AB  - Poly(ADPR) polymerase (PARP; EC 2.4.2.30) is a nuclear enzyme, which, when
      activated by oxygen- and nitrogen-radical-induced DNA strand breaks, transfers
      ADP ribose units to nuclear proteins and initiates apoptosis by depletion of
      cellular NAD and ATP pools. The present study investigates whether the oxidative
      stress-dependent activation of PARP plays a role in the etiopathogenesis of
      arthritis. The antiarthritic reactivity of the biogenic PARP inhibitor
      nicotinamide was tested in DBA/1 x B10A(4R) mice suffering from potassium
      peroxochromate-induced arthritis. Daily doses of 4 mmol/kg of NA suppressed the
      arthritis by 35% and inhibited the phagocytic generation of reactive oxygen
      species, which increases sixfold during the development of arthritis. The onset,
      progression, and remission of arthritis correlated positively to the phorbolester
      activated respiratory burst of neutrophils and monocytes, and a dose-dependent
      inhibition of NADPH oxidase activity was determined with human phagocytes. Our
      data support the hypothesis that oxidative stress-induced alterations in cellular
      signal transduction pathways play a pivotal role in the development of arthritis,
      which can be suppressed by the simultaneous inhibition of poly(ADPR) polymerase
      and NADPH oxidase.

PMID- 7628864
TI  - Differential induction of stress proteins and functional effects of heat shock in
      human phagocytes.
AB  - Induction of specific heat shock (HS) proteins (HSP) has been described as a
      response of human monocytes to phagocytosis, and HSP may play protective roles in
      infection and immunity. Here we compared the stress response in monocytes and
      polymorphonuclear neutrophils during exposure to the classical inducers of HSP,
      i.e., HS and cadmium. We also investigated the stress response in these two
      phagocytic cells after particulate (phagocytosis) and nonparticulate [f-Met-Leu
      Phe (FMLP)] activation of the respiratory burst enzyme NADPH oxidase. HS and
      cadmium induced stress protein synthesis in both cell types. In contrast,
      phagocytosis induced HSP in monocytes only, while FMLP did so in neutrophils
      only. This differential regulation of stress proteins might relate to
      physiological and functional differences between monocytes and neutrophils. With
      respect to functional effects of HS, we examined, in human monocytes and in
      neutrophils, the effect of HS on NADPH oxidase-mediated O2- generation as well as
      on phagocytosis, bacterial killing, and superoxide dismutase (SOD) activity. In
      monocytes, as in neutrophils, NADPH oxidase activity was inhibited by HS, while
      thermotolerance prevented this inhibition. Phagocytosis and bacterial killing
      were unaltered by HS. SOD activity transiently increased in monocytes but
      decreased in neutrophils upon exposure to HS. These observations indicate
      differential induction of HSP in human phagocytes and differential regulation of
      phagocytes' functions by HS.

PMID- 7628866
TI  - Molecular events underlying schistosomiasis-related bladder cancer.
AB  - Twenty-one invasive squamous-cell carcinomas (SCC) of the bladder from
      Schistosoma-hematobium-infected patients were examined immunohistochemically for
      the expression of p53, Rb, EGFR and c-erbB-2 proteins; and screened by single
      strand conformation polymorphism and sequencing for mutations in the ras (H, N,
      K) codon hotspots (12, 13, 61) and p53 (exons 4-9) genes. Positive staining for
      p53, EGFR and c-erbB-2 was reported in 38, 67 and 28% of tumors respectively.
      Only one of the tumors, the only one that was poorly differentiated, displayed an
      absence of nuclear Rb staining. Ras alterations were detected in the H-ras gene
      in 3 tumors, 2 of which harbored a codon-13 (Gly-->Arg) and one a codon-12 (Gly-
      >Ser) point mutation. p53 mutations were recorded in 12 tumors (57%), 6 of which
      stained positively for p53. Four tumors had exon-7 mutations (codons 235, 241 and
      249; one tumor had 2 exon-7 mutations). Eight tumors were mutated in exon 8
      (codons 264, 271, 273, 285, 286, 288 and 294), 5 of which harbored multiple
      mutations. One tumor had an insertion/deletion event in exon 9. The frequency of
      detection of over-expression of EGFR and c-erbB-2 in bilharzial-bladder lesions
      is comparable to that reported in TCC, contrasting with the infrequent loss of Rb
      expression found in invasive lesions associated with schistosomiasis infection.
      However, the detection of multiple p53 mutations in these lesions is suggestive
      of the involvement of a carcinogenic agent with maintenance of preferential
      activation of the H-ras gene.

PMID- 7628867
TI  - DNA methylation status of the MUC1 gene coding for a breast-cancer-associated
      protein.
AB  - The MUC1 gene codes for protein products that are highly expressed in human
      breast-cancer tissue and that serve as tumor markers for disease progression. The
      factors contributing to the disease-specific over-expression of the MUC1 gene are
      under intensive investigation and are yet to be determined. A large transcribed
      region of the human MUC1 gene is a CpG island that consists of 60-bp tandemly
      repeating units, each of which contains one SmaI restriction site. The
      methylation status of regulatory regions, upstream to the transcriptional start
      site, is essential for the regulation of gene expression. We therefore evaluated
      whether the methylation status of the various regions of the MUC1 gene may affect
      its expression. Using SmaI, and its isoschizomer XmaI endonucleases, we
      demonstrated that in peripheral-blood leukocytes (PBL-DNA) that do not express
      the MUC1 gene, the repeat array is completely methylated, whereas the same
      sequences are entirely non-methylated in breast-tumor-tissue DNA (BT-DNA). In
      contrast, sequences upstream and downstream to the repeat array showed no
      difference in the methylation pattern in PBL-DNA and BT-DNA. Hypomethylation
      within the repeat array was also observed in other epithelial tissues that
      express the MUC1 gene at much lower levels to those seen in breast-cancer tissue.
      These studies demonstrate that hypomethylation of the tandem repeat array is an
      absolute requirement for MUC1 gene expression in epithelial tissues, although in
      breast-cancer tissue additional regulatory mechanisms must pertain for its over
      expression.

PMID- 7628868
TI  - Expression and release of intercellular adhesion molecule-1 in renal-cancer
      patients.
AB  - We examined ICAM-1 expression in 37 freshly dissociated renal-cancer cell
      populations. Immunoperoxidase analysis revealed that 31 of the 37 renal tumors
      expressed ICAM-1 to various degrees; ICAM-1 expression was significantly lower in
      tumor cells obtained from patients remaining tumor-free after a median follow-up
      of 60 months (mean value 24.4% +/- 21) than in tumor cells obtained from the
      relapsed patients (mean value 40.8% +/- 22), and the low expression of this
      molecule on the cell surface seemed to correlate with favorable clinical
      behavior. In 41 patients, the mean level of sICAM-I was 551 +/- 260 ng/ml,
      significantly higher than normal. However, sICAM-1 levels were significantly
      lower in the 20 tumor-free (mean 467 +/- 158 ng/ml) than in the 21 metastatic
      patients (mean 631 +/- 318 ng/ml). Eleven renal-cancer cell populations were
      cultured in order to examine the expression and release of ICAM-1. All of these
      cells were positive for ICAM-1 expression, which was elevated in 6 cases (> 50%)
      and low in the remaining 5 cases (18-35%). However, only the 5 cell populations
      expressing low levels of ICAM-1 released this molecule, showing an inverse
      correlation with cellular expression. Five of the cell populations were treated
      for 48 hr with rIFN-gamma, in these cells, both ICAM-1 expression and sICAM-1
      levels increased, although sICAM-1 levels in the supernatants of the cell
      populations with constitutive high ICAM-1 expression remained very low.

PMID- 7628869
TI  - Differential effects of verapamil and quinine on the reversal of doxorubicin
      resistance in a human leukemia cell line.
AB  - We studied the restoration of doxorubicin accumulation and sensitivity by
      verapamil and quinine in a variant of the human erythroleukemia cell line K562
      selected for resistance to doxorubicin and presenting a multidrug-resistance
      (MDR) phenotype. Verapamil was able to completely restore doxorubicin
      accumulation in the resistant cells to the level obtained in sensitive cells, but
      only partially reversed doxorubicin resistance. Quinine, in contrast, had a
      relatively weak effect on doxorubicin accumulation but was able to completely
      restore doxorubicin sensitivity in the resistant cells. In addition, verapamil
      was able to decrease azidopine binding to P-glycoprotein, whereas quinine was
      not. Quinine also modified the intracellular tolerance to doxorubicin, which
      suggests that it is able to modify drug distribution within the cells. Confocal
      microscopy revealed that verapamil and quinine were able to restore nuclear
      fluorescence staining of doxorubicin in resistant cells; since this was obtained
      for quinine without significant increase of doxorubicin accumulation, this
      observation confirms that quinine acts principally on doxorubicin redistribution
      within the cells, allowing the drug to reach its nuclear targets. When used in
      association, verapamil and quinine reversed doxorubicin resistance in a
      synergistic fashion. We conclude that verapamil and quinine do not share the same
      targets for reversal of MDR in this cell line; whereas verapamil directly
      interferes with P-glycoprotein and mainly governs drug accumulation, quinine has
      essentially intracellular targets involved in drug redistribution from
      sequestration compartments.

PMID- 7628870
TI  - Effect of different platelet agonists on intracellular free Ca++ concentrations
      in human tumor cells: possible role in tumor growth.
AB  - Modulation of cytoplasmic Ca++ concentration is a mechanism common to signal
      transduction pathways regulating many cellular phenomena, including the
      interactions of tumors with the hemostatic system. We have investigated the pro
      aggregating and pro-coagulant activities of human tumor cell lines cultured in
      vitro and the ability of different platelet agonists to induce Ca++ transients in
      these cells. Cells of a malignant mesothelioma line activated platelets by a
      thrombin-dependent mechanism; on the contrary, HeLa cells, derived from a uterine
      cervical cancer, possessed ADP-dependent pro-aggregating activity, and DND-IA
      melanoma cells did not stimulate platelet aggregation. All cell lines showed a
      tissue-factor-like procoagulant property, more pronounced in mesothelioma cells.
      Furthermore, ADP was able to induce a transient increase in cytoplasmic Ca++
      concentration in tumor cells from all lines; collagen showed this effect in
      mesothelioma cells and in HeLa cells, and thrombin was effective only in
      mesothelioma cells. PAF never induced Ca++ fluxes in any of the cell lines
      investigated. Finally, the calcium-channel blocker verapamil inhibited agonist
      induced Ca++ transients in tumor cells and in vitro tumor-cell growth. These data
      may help to identify new possible mechanisms of the 2-way interaction of tumors
      with the hemostatic system.

PMID- 7628871
TI  - An in vivo model of intratumoural aromatase using aromatase-transfected MCF7
      human breast cancer cells.
AB  - About two-thirds of human breast carcinomas contain detectable levels of
      aromatase, the enzyme which converts androgens to oestrogens. Assessment of the
      importance of this enzyme to breast cancer growth has been hampered by the
      absence of an adequate model system. We have previously reported that MCF7 human
      hormone-dependent breast cancer cells transfected with human aromatase cDNA
      (Arom1 cells) showed a growth response in vitro to exogenous androgens and this
      effect was blocked by aromatase inhibitors. We report here our use of these cells
      to develop a xenograft model in athymic nude mice. Neither MCF7 cells nor Arom1
      cells formed tumours in oophorectomised (ovx) nude mice unless provided with
      oestradiol (E2) support. Once established, Arom1, but not MCF7, tumours could be
      grown in ovx females supplemented with androstenedione (delta 4A). The mean
      plasma level of delta 4A was 14 nmol/L in supplemented animals and < 0.5 nmol/L
      in unsupplemented animals. Similarly, unsupplemented male nude mice were able to
      support the growth of Arom1 tumours but not MCF7 tumours. The potent and highly
      specific aromatase inhibitor CGS20267 (letrozole) significantly decreased tumour
      growth at 2 mg/kg/day and completely inhibited growth at 20 mg/kg/day in delta 4A
      supplemented but not E2-supplemented animals. Our results indicate that delta 4A
      dependent growth of Arom1 tumours in vivo is mediated through the action of
      intratumoural aromatase. This model should allow an assessment of the critical
      levels of aromatase required for tumour growth support.

PMID- 7628872
TI  - Treatment of Wistar rats with a renal carcinogen, ferric nitrilotriacetate,
      causes DNA-protein cross-linking between thymine and tyrosine in their renal
      chromatin.
AB  - Ferric nitrilotriacetate (Fe-NTA) induces renal proximal tubular damage
      associated with lipid peroxidation and oxidative DNA base modifications that
      finally leads to a high incidence of renal adenocarcinoma in rodents. In the
      present study, we report on the in vivo formation of DNA-protein cross-links
      (DPCs) involving thymine and tyrosine in the renal chromatin of Wistar rats
      treated with single or repeated i.p. administration of Fe-NTA. Analyses of
      chromatin samples by gas chromatography/mass spectrometry revealed a significant
      increase in the amount of 3-[(1,3-dihydro-2,4-dioxopyrimidin-5-yl)-methyl]-L
      tyrosine (Thy-Tyr cross-link) 24 and 48 hr after the administration of Fe-NTA. At
      19th day of Fe-NTA treatment, the amount of Thy-Tyr cross-link decreased to the
      control level, indicating the presence of cellular repair activity. Thy-Tyr cross
      link may play a role in the genetic alteration of this renal carcinogenesis
      model, since mitoses for regeneration of renal proximal tubules were closely
      associated with the increase in DPCs.

PMID- 7628873
TI  - Increased experimental pulmonary metastasis in pregnant mice.
AB  - The effect of pregnancy on experimental pulmonary metastasis was studied.
      Compared to the incidence of pulmonary metastasis induced by G6 cells in non
      pregnant mice, the incidence of such metastasis was found to be greatly enhanced
      when the cells were injected i.v. in the latter half of pregnancy. The maximum
      enhancement was seen on the 15th day of pregnancy. The incidence of pulmonary
      metastasis returned to the level observed in non-pregnant mice when the cells
      were injected 4 days after parturition. Pregnancy also significantly increased
      the incidence of pulmonary metastasis of 2 other cell lines (3LL and Colon 26).
      Injection of G6 cells after hysterectomy performed on the 15th day of pregnancy
      resulted in decreased lung colonization, similar to that seen after parturition.
      Quantificative analysis of the arrest of G6 cells labeled with [125I]-5-iodo-2'
      deoxyuridine in the lungs showed that the tumor-cell clearance from the lungs
      during the 24-72 hr after tumor-cell injection was much slower in pregnant than
      in non-pregnant mice. The continuous administration of beta-estradiol and/or
      progesterone, which maintained serum levels of the hormones equivalent to those
      prevailing on the 15th day of pregnancy, did not affect the lung colonization of
      G6 cells. Tumor-cell-platelet aggregation was more extensive with platelets
      obtained from mice at the 15th day of pregnancy than with those from non-pregnant
      mice. When platelets isolated from pregnant mice were injected into normal mice 5
      min before G6 injection, lung metastasis was also enhanced. These findings
      suggest that a pregnant host is handicapped with regard to pulmonary metastasis,
      this being partly due to increased platelet-aggregating activity in response to
      tumor cells.

PMID- 7628874
TI  - Engineering high affinity humanized anti-p185HER2/anti-CD3 bispecific F(ab')2 for
      efficient lysis of p185HER2 overexpressing tumor cells.
AB  - We previously constructed a humanized anti-p185HER2/anti-CD3 bispecific antibody
      variant, BsF(ab')2 v1 which retargets the cytotoxic activity of human T cells in
      vitro against human breast tumor cells which overexpress the p185HER2 product of
      the HER2/neu (c-erbB-2) protooncogene. Subsequently we identified an improved
      anti-CD3 variant, v9, which binds to T cells with approx. 100-fold higher
      affinity than the original variant, v1. Here we demonstrate that BsF(ab')2 v9 is
      more potent than BsF(ab')2 v1 in stimulating the proliferation of both resting
      peripheral blood lymphocytes (PBL) and IL-2-activated, long-term cultured T
      lymphocytes (ATL). In addition, at low concentrations (0.01-1 ng/ml) BsF(ab')2 v9
      is much more efficient than BsF(ab')2 v1 in directing lysis of p185HER2
      overexpressing tumor cells by IL-2 activated PBL. In contrast, at higher
      concentration BsF(ab')2 v9 and BsF(ab')2 v1 have similar potency in retargeted
      cytotoxicity. At BsF(ab')2 v9 concentrations of > or = 1 ng/ml the susceptibility
      of p185HER2-expressing tumor cells to lysis is apparently independent of the
      level of p185HER2 expression. At lower concentrations of BsF(ab')2 v9 and/or
      lower ratios of effector to target cells the extent of lysis is reduced, in some
      cases improving the selectivity of lysis of high p185HER2 expressors over low
      expressors. Thus selection of a high affinity anti-CD3 arm is likely important in
      the design of BsF(ab')2 for retargeting the cytotoxicity of T cells to tumors.
      The dose of BsF(ab')2 v9 in any future clinical evaluation will require
      optimization to maximize anti-tumor efficacy whilst minimizing potential toxicity
      against normal tissue expressing p185HER2.

PMID- 7628875
TI  - Identification of differentially expressed genes in T-lymphoid malignancies in an
      animal model system.
AB  - The molecular events characterizing lymphoid malignancy have been examined in an
      animal model system, specifically, the retroviral induction of leukemia and
      lymphoma in the domestic cat following infection with feline leukemia virus
      (FeLV). Genes differentially expressed in FeLV-induced lymphomas were isolated
      using a strategy of differential hybridization. Six genes were identified which
      demonstrate a higher level of expression in an FeLV-induced feline thymic tumor
      as compared with normal thymus. The differentially expressed genes encode the
      feline homologues of ribosomal proteins S3a, S4, S17, and L41, elongation factor
      1 alpha, and cytochrome oxidase sub-unit I. Northern-blot analysis and
      quantification by phosphorimaging demonstrates that these genes are expressed at
      levels from 1.5- to 3.1-fold higher in J5-1 thymic tumor as compared with normal
      thymus. Expression of the selected ribosomal protein mRNA was further examined in
      a series of human and feline tissues, including normal tissues, malignant tumors
      and cell lines. Our data reveal that elevation of the selected ribosomal protein
      mRNA is associated with all FeLV-induced thymic lymphomas examined. The
      differentially expressed ribosomal protein mRNA accumulates in a balanced manner
      in thymic lymphomas. By contrast, the elevation in ribosomal protein mRNA levels
      is not associated uniformly with hematopoietic malignancy. T-lymphoid malignancy,
      solid tumors or actively proliferating cells. Rather, the elevation appears to be
      a uniform and distinctive feature of T-cell malignancy of this particular type.
      The elevated expression of these genes may be causally related to the neoplastic
      process.

PMID- 7628876
TI  - Manifestations of cancer cachexia induced by colon 26 adenocarcinoma are not
      fully ascribable to interleukin-6.
AB  - In order to further clarify the role of interleukin 6 (IL-6) in the pathogenesis
      of cachexia, recombinant human IL-6 (hIL-6) was administered s.c. by osmotic pump
      for 9 days at a dose of 1 or 10 micrograms/day into CDF1 mice inoculated with a
      non-cachexia-inducing subclone of colon 26 adenocarcinoma (clone 5), or with a
      cachexia-inducing subclone (clone 20) of this malignancy. The serum level of IL-6
      in non-cachectic mice with clone-5 tumors was 35% lower than in cachectic mice
      bearing clone 20 of colon 26 adenocarcinoma on the 19th day after tumor
      inoculation. IL-6 administration induced anemia, thrombocytosis and visceral
      organ hypertrophy not only in mice with clone-5 tumors but also in control mice
      with no tumor burden. Lipolysis and proteolysis became conspicuous when a large
      dose (10 micrograms/day) of IL-6 was infused into mice with clone-5 tumors.
      However, IL-6 supplementation did not induce loss of body weight, a decline in
      food intake or lymphocytopenia, which were characteristically observed in
      cachectic mice with clone-20 tumors. In conclusion, IL-6 appears to be a
      permissive factor for the development of cachexia but, while it can induce some
      of the symptoms typical of cachexia, it cannot in itself induce the full
      cachectic syndrome.

PMID- 7628877
TI  - Cinnamic acid: a natural product with potential use in cancer intervention.
AB  - Cinnamic acid, a naturally occurring aromatic fatty acid of low toxicity, has a
      long history of human exposure. We now show that cinnamic acid induces cytostasis
      and a reversal of malignant properties of human tumor cells in vitro. The
      concentration causing a 50% reduction of cell proliferation (IC50) ranged from 1
      to 4.5 mM in glioblastoma, melanoma, prostate and lung carcinoma cells. Using
      melanoma cells as a model, we found that cinnamic acid induces cell
      differentiation as evidenced by morphological changes and increased melanin
      production. Moreover, treated cells had reduced invasive capacity associated with
      modulation of expression of genes implicated in tumor metastasis (collagenase
      type IV, and tissue inhibitor metalloproteinase 2) and immunogenicity (HLA-A3,
      class-I major histocompatibility antigen). Further molecular analysis indicated
      that the anti-tumor activity of cinnamic acid may be due in part to the
      inhibition of protein isoprenylation known to block mitogenic signal
      transduction. The results presented here identify cinnamic acid as a new member
      of the aromatic fatty acid class of differentiation-inducers with potential use
      in cancer intervention.

PMID- 7628878
TI  - Administration of disulfide-stabilized Fv-immunotoxins B1(dsFv)-PE38 and B3(dsFv)
      PE38 by continuous infusion increases their efficacy in curing large tumor
      xenografts in nude mice.
AB  - B1 (dsFv)-PE38 and B3(dsFv)-PE38 are recombinant immunotoxins in which the Fv
      fragments of MAbs B1 and B3, respectively, are stabilized by an engineered
      interchain disulfide bond and are fused at their C-termini to a modified
      Pseudomonas exotoxin from which the cell-binding domain has been deleted (PE38).
      Both immunotoxins have been shown to be specifically cytotoxic toward human
      cancer cell lines which express Le gamma-related carbohydrates on their surface,
      and when given i.v., eradicated 30- to 50-mm3 s.c. A431 tumors growing in nude
      mice. A major advantage of dsFv-immunotoxins is their stability at 37 degrees C
      compared with the relatively unstable single-chain Fvs. This allows them to be
      given continuously by osmotic pumps placed in the peritoneal cavity. In an
      attempt to increase the therapeutic index of the immunotoxins, we have now
      delivered them continuously for 6 days through mini-osmotic pumps placed in the
      peritoneal cavity of tumor-bearing nude mice. Using this mode of administration,
      we were able to maintain a constant level of immunotoxin in the serum which was
      non-toxic to the mice, but caused complete regressions of large 150- to 200-mm3
      tumors which lasted for over a month at 1/11 of the LD50 with B1(dsFv)-PE38 and
      1/6 of the LD50 with B3(dsFv)-PE38. Complete regression of tumors of similar size
      could also be achieved by i.v. bolus injections of these immunotoxins at 1/7 of
      the LD50 with B1(dsFv)-PE38) and 1/3 of the LD50 with B3(dsFv)-PE38. These
      results suggest that in patients it may be advantageous to administer dsFv
      immunotoxins by continuous infusion, since a larger therapeutic index is
      achieved.

PMID- 7628880
TI  - Hodgkin's disease and parity.

PMID- 7628879
TI  - Interleukin-11 protects the clonogenic stem cells in murine small-intestinal
      crypts from impairment of their reproductive capacity by radiation.
AB  - The rapidly proliferating gastrointestinal mucosa is one of the major limiting
      tissues in cancer therapy. Because of its short transit time and high sensitivity
      to radiation and chemotherapeutic drugs, damage is rapidly manifested. Protection
      of the important stem cells in the tissue could be achieved, in principle, by
      appropriate prior manipulation with cytokines or growth factors which might make
      them more resistant to the cytotoxic treatment, for example, by putting them out
      of cycle. Such strategies might reduce some of the adverse side-effects of cancer
      treatment and improve the quality of life of patients, while possibly allowing an
      escalation of therapeutic dose. The functional capacity of stem cells has been
      studied for many years using a microcolony assay technique which measures the
      regenerative capacity of the clonogenic stem cells in crypts. These cells
      determine the survival of crypts which themselves determine whether or not the
      mucosal integrity is maintained and ultimately whether the animal or patient
      survives. Here, we demonstrate that treatment with interleukin-11 for 2 days
      prior to radiation exposure can significantly increase the number of surviving
      crypts. Treatment with IL-11 both before (for 2 days) and after irradiation (for
      3 days) produces a slightly enhanced protection. Up to about 4 times more crypts
      survive at the highest radiation dose after either of these treatment schedules.
      These studies may provide a radiobiological explanation for the increased
      survival of animals when IL-11 is administered during 5FU and radiation
      exposures.

PMID- 7628881
TI  - Preventive actions of Terminalia belerica in experimentally induced
      atherosclerosis.
AB  - Hypercholesterolaemia and atherosclerosis were induced experimentally in rabbits
      by cholesterol feeding. The effect of an indigenous drug, T. belerica, was
      evaluated in these hypercholesterolemic rabbits. T. belerica reduced the levels
      of lipids in hypercholesterolemic animals. There was also a significant decrease
      in liver lipids and heart lipids (P < 0.05) in the drug-treated animals.

PMID- 7628882
TI  - The influence of decreased left-ventricular afterload on cardiac morphology in
      hypertrophied rat hearts.
AB  - The influence of afterload reduction on cardiac morphology was investigated in
      Goldblatt rats (hypertensive Wistar rats) with left-ventricular hypertrophy. The
      measurements were performed on a modified heart-lung preparation in which left
      ventricular afterload was reduced either 0%, 15%-30% or 35%-50%. Goldblatt rats
      without heart-lung preparation served as control group. The aim of this study was
      to investigate the effects of decreased left-ventricular afterload on the
      myocardial morphology. The hearts were prepared for light and electron
      microscopy. For ultrastructural investigations, we developed a mitochondrial
      alteration score and graded the myocytes according to the degree of ischemic
      injury. The changes ranged from score 0 (normal) to score 4 (most severe). The
      mean score of the group with marked afterload reduction (35%-50%) was
      significantly increased compared to all other groups. Our data suggest that
      marked afterload reduction has a negative impact on the myocardial ultrastructure
      in hypertension-induced left-ventricular hypertrophy. Light microscopically, we
      found a correlation between myocardial cell diameter and blood pressure and a
      significant difference in arterial wall thickness between normotensive and
      hypertensive rats.

PMID- 7628884
TI  - Intermittent mitral regurgitation and pulmonary edema after aortic valve
      replacement.
AB  - We report intermittent mitral valve regurgitation with 17 acute pulmonary edemas
      over a 16-month period after aortic valve replacement due to combined aortic
      valve disease in a 51-year-old man. The mechanism of mitral regurgitation was
      explained by the relatively large size of the prosthetic valve which had had to
      be sutured partly below the aortic annulus. It was suspected to interfere with
      the closure of the mildly diseased mitral valve when under pressure or subjected
      to volume loadings of the left ventricle which provoked free mitral
      regurgitation. There was no recurrence of pulmonary edema in the 50 months
      following mitral valve replacement.

PMID- 7628883
TI  - Angiographic, intravascular ultrasound and functional findings early after
      orthotopic heart transplantation.
AB  - Accelerated graft atherosclerosis is responsible for increased mortality and
      morbidity among heart transplant recipients. The aim of this in-vivo study was to
      evaluate coronary atherosclerotic vessel alterations and endothelial function.
      Seventeen patients (14 males; mean age 49.3 years; range 24 to 69) were studied
      an average of 11 weeks (range 5 to 21) after heart transplantation because of
      coronary artery disease (n = 8), dilative cardiomyopathy (n = 7), mitral valve
      replacement (n = 1) and left atrial metastases of a leiomyosarcoma (n = 1). Mean
      age of the donor hearts (9 males) was 29 years (range 12 to 55). All recipients
      underwent biplane ventriculography and coronary angiography. In this study
      population, a total of 120 coronary segments (main stem, 21; left anterior
      descending artery, 85; circumflex artery, 14) were analyzed by intravascular
      ultrasound (20 MHz, 3.5F). In 13 patients, acetylcholine was infused into the
      proximal left anterior descending artery (10(-8) to 10(-5) M) to evaluate
      vasomotion within this segment. Regional contraction abnormalities were
      documented in 2 patients. Nine segments angiographically showed non-critical
      stenoses (5 patients). Intravascular ultrasound detected 52 cross-sectional areas
      with a three-layer pattern indicating intimal thickening. Mean circumferential
      extension of intimal proliferation was 192 degrees, mean intimal thickness 0.35
      mm. Only 5 segments of the sonographically pathological cross-sectional areas
      showed angiographical evidence of atherosclerotic lesions. Intracoronary
      administration of acetylcholine at doses of 10(-8) and 10(-7) M resulted in
      vasoconstriction of the examined coronary segment in only 2 patients; the
      intracoronary application of acetylcholine at doses of 10(-6) and 10(-5) M
      revealed coronary vasoconstriction in 10 of the total of 13 patients. Using
      intravascular ultrasound, coronary artery lesions in heart transplant recipients
      can already be depicted at a very early stage. The abnormal response to
      acetylcholine in most of the heart recipients is independent of the extent of
      atherosclerotic vessel abnormalities documented by ultrasound or angiography.

PMID- 7628885
TI  - Characteristics and prognosis of non-participants of a multi-centre trial of long
      term anticoagulant treatment after myocardial infarction.
AB  - Participants of a randomised trial may differ from eligible non-participants as a
      result of selection. We studied the distribution of prognostic factors and
      survival in eligible patients of a multi-centre trial of long-term oral
      anticoagulant treatment after myocardial infarction. All hospital survivors of
      myocardial infarction in one participating clinical centre of a multi-centre,
      randomised, double-blind, placebo-controlled trial of long-term anticoagulant
      treatment after myocardial infarction were screened for entry criteria.
      Subsequently, prognostic factors and survival of participants were compared with
      eligible but not randomised patients. The 350 participants were younger and were
      more often of male gender and more often smokers compared with 587 non
      participants. Non-participants had more frequently suffered a previous myocardial
      infarction and were treated more often with diuretics and ACE-inhibitors,
      suggesting a higher proportion of patients with chronic heart failure in this
      group. Age, previous myocardial infarction and the use of diuretics at discharge
      were independent predictors of mortality, consent showed no association. Our
      findings indicate that participants of a clinical trial have a better prognosis
      during the first years following myocardial infarction compared to eligible non
      participants as a result of a higher prevalence of cardiovascular risk factors
      associated with mortality in the non-participants.

PMID- 7628886
TI  - Assessment of a circuit of exercises through heart rate response.
AB  - OBJECTIVE: A circuit of seven exercises was designed for a cardiac population.
      This study evaluated whether the patients achieved their training heart rate
      during the circuit, recommended to be 70-85% of the maximum heart rate achieved
      during an exercise test. DESIGN: Patients were randomly allocated to a starting
      exercise to balance any order effect from performing the exercises in a given
      sequence. Each of the seven exercises was performed for 30 s, so one circuit
      lasted 3.5 min. The circuit was repeated five times. PATIENTS: Twenty patients
      who had had myocardial infarctions within 6 weeks of the study participated.
      OUTCOME: Heart rate was measured to assess the stress placed on the
      cardiorespiratory system during the circuit. Measurements were taken at 10 and 20
      s following the termination of each exercise and over two repetitions of the
      circuit (a total of 14 exercise periods). RESULTS AND CONCLUSION: Comparisons of
      the readings taken at 10 and 20 s indicated, contrary to previously published
      findings, that no significant heart rate deceleration occurred within this
      period. Every exercise maintained the mean heart rate within the specified band
      of 70-85% of the maximum heart rate achieved during the exercise test. The study
      has shown that the selected exercises were suitable for use during a cardiac
      rehabilitation programme.

PMID- 7628887
TI  - Chemical cardioversion of atrial fibrillation with intravenous dofetilide.
AB  - We studied the effects of two active dose levels of dofetilide (8 and 12
      micrograms/kg) and placebo in 16 patients with recent onset atrial fibrillation.
      The study was of a crossover design such that all patients received a therapeutic
      agent, 15 patients completed the study. Cardioversion was achieved in 2/6
      patients receiving 8 micrograms/kg dofetilide and in 2/9 patients receiving 12
      micrograms/kg. No patients cardioverted as a result of the placebo infusion. Two
      patients who cardioverted suffered episodes of torsades de pointes following the
      active drug. Electrical cardioversion was attempted in eight patients who
      remained in atrial fibrillation and was successful in six. The average duration
      of atrial fibrillation was 35 days in those who cardioverted and 83 days in those
      who did not. The compound appears to have only limited effect in cardioversion of
      atrial fibrillation of moderate duration.

PMID- 7628888
TI  - Visualization of pulmonary vein obstruction by pulmonary artery wedge injection
      and documentation by pressure tracings: report of one case with persistent
      wheezing following correction of total anomalous pulmonary venous connection.
AB  - A 21-month-old boy presented with persistent wheezing 16.5 months after cardiac
      surgery for supracardiac total anomalous pulmonary venous connection. He had
      presented at birth with cyanosis and at the age of 25 days, underwent initial
      cardiac surgery in the form of anastomosis of the pulmonary venous confluence to
      the left atrium. Non-invasive investigations including transthoracic and
      transesophageal echocardiograms revealed stenosis of the right pulmonary veins.
      Visualization and documentation of right pulmonary vein obstruction by pulmonary
      arterial wedge angiography and pressure tracings are presented.

PMID- 7628889
TI  - Hypovolemic shock and mortality after ingestion of Tripterygium wilfordii hook
      F.: a case report.
AB  - Tripterygium wilfordii Hook F (TWHF) is a kind of Chinese herbal medicine used
      for 2000 years. It was applied externally for treatment of arthritis and
      inflammatory tissue swelling in early years. Recently, this drug has been found
      to have immunosuppressive effects which could successfully induce remission of
      some autoimmune disorders without obvious adverse effects. Although there are
      side effects of gastrointestinal upset, infertility and suppression of lymphocyte
      proliferation, little information about lethal toxicities has been reported. A
      case is presented here of a previously healthy young man who developed profuse
      vomiting and diarrhea, leukopenia, renal failure, profound hypotension and shock
      after ingestion of an extract of TWHF. In addition to his hypovolemic shock,
      serial electrocardiograms (ECG), cardiac enzyme studies, and echocardiography
      also showed some evidence of coexisting cardiac damage. He died of intractable
      shock 3 days after the abuse of TWHF. Further studies of the pathogenesis of
      peripheral collapse and possible cardiac toxicity, and determination of the
      therapeutic range of this drug are necessary before it is used extensively.

PMID- 7628890
TI  - Fluoxetine and ventricular torsade--is there a link?

PMID- 7628891
TI  - Infarct size limitation: acute N-acetylcysteine defense (ISLAND) trial. Start of
      the study.

PMID- 7628892
TI  - Peer review.

PMID- 7628893
TI  - In the wake of Heinz Hartmann.
AB  - This study of Heinz Hartmann's contributions emphasises change within continuity.
      Specifically, it is argued that he both integrated and changed significantly
      Freud's structural theory--his 'ego psychology'. This he did through his then
      modern concept of adaptation. In turn, adaptation paved the way towards further
      change in the direction of current emphases on dialogue and intersubjectivity.
      These new developments have contributed beneficially to theory and clinical
      practice, but, like all new developments, they have introduced new problems,
      among them unreflective and undisciplined eclecticism. Consideration is given to
      the incompleteness inherent in theory construction. In psychoanalysis, the new,
      object-related developments require as a complement some version of the type of
      structural theorising initiated by Freud and developed to its highest point by
      Hartmann and his close collaborators particularly; in meeting that requirement,
      some version of an objectivist stance is also required to complement the
      subjectivism and pluralism of the newer developments. Throughout this
      appreciation of Hartmann's role in the history of psychoanalytic thought, an
      effort is made to undo the negative effects of misreadings that took his ideas on
      adaptation and ego psychology to mean an endorsement of superficial adjustment or
      conformity and an overvaluation of conscious mental processes.

PMID- 7628894
TI  - Freud and the history of empathy.
AB  - Empathy (Einfuhlung) has a long history in aesthetics, psychology and
      psychoanalysis, and plays a greater role in Freud's thinking than readers of the
      Standard Edition realise. Coined by Robert Vischer in 1873, Einfuhlung originally
      designates the projection of human feeling on to the natural world. For a quarter
      of a century the term remains at the centre of psychological aesthetics before
      Theodor Lipps, a philosopher admired by Freud for 40 years, transfers it to
      psychology in an attempt to explain how we discover that other people have
      selves. Freud's conception of Einfuhlung, first developed in 'Jokes and their
      Relation to the Unconscious' (1905), remains heavily intellectual throughout his
      career; he views it as the process that allows us to understand others by putting
      ourselves in their place. Although the Standard Edition never translates
      Einfuhlung as 'empathy' in a clinical context, Freud regards it as essential for
      establishing the rapport between patient and analyst that makes interpretation
      possible. This paper traces the history of Einfuhlung from aesthetics and
      psychology to Freud and his contemporaries.

PMID- 7628895
TI  - Concern: spurious or real.
AB  - This paper is about a group of patients who appear to show excessive concern for
      their objects, reflecting a combination of a real wish for reparation alongside
      an attitude of hostility and superiority towards the object. Detailed clinical
      examples from two patients are used to illustrate a certain combination of
      characterological defences in these patients who have been severely deprived, and
      overcompensate for this experienced deprivation by the expression of excessive
      concern for an object that is simultaneously experienced as hostile and
      frustrating. Side by side with the partial achievement of the depressive position
      there is an early 'take over' of the breast, in which the infant 'becomes' the
      breast and shows behaviour which is in part a fake of a very concerned mother.
      The paper includes a discussion of some of the technical problems in dealing with
      such patients, and stresses the need for distinguishing between what is real and
      what is false; it suggests that what is required is a balanced or 'two handed'
      approach, in which there is firm handling of the manic or pretentious 'take over'
      together with a sympathetic understanding of the underlying vulnerability of
      these patients.

PMID- 7628896
TI  - The psychoanalyst's mind: from listening to interpretation--a clinical report.
AB  - Freud's delineation of 'psychical reality' as our investigative domain poses
      compelling epistemological and clinical challenges, which must profoundly affect
      our understanding of what is meant by what is real. Exploring the patient's inner
      reality as our central database, we are given a remarkable, but elusive
      opportunity for discovery and recognition, holding a pervading mutative power. It
      is elusive, for, despite our intentions otherwise, there is a continuing pull
      towards a belief in the greater 'wisdom' of our own assumptions and
      predilections, a blurring of the boundaries between our and our patient's vantage
      points, leading us away from essential, if subtler dimensions of the patient's
      experience. Utilising a clinical example, the author tries to illustrate some of
      her efforts to listen to her patient, and the difficulty she encountered. Her
      struggle was one which, she believes, has more far-ranging, even ubiquitous
      ramifications. Further consideration is given to some of the theoretical
      underpinnings in this mode of analytic listening.

PMID- 7628897
TI  - The unfinished manuscript in the drawer: observations on the analysis of a type
      of symptom.
AB  - The interminable project, such as an unfinished manuscript in the drawer, is a
      familiar affliction in populations of writers, artists and intellectuals. An
      unrelenting absorption in such a project consuming whole decades of one's life
      distinguishes this plight from more benign varieties of work inhibition. The
      interminable project lends itself to a real dilemma of a double life. A case of a
      female writer and lecturer is presented, in which a longstanding unfinished
      manuscript figures as a principal complaint. In addition to familiar
      developmental conflicts, which psychoanalysis finds in psychopathologies of
      ambition and achievement, the analysis of this patient called for particular
      attention to various gains of the symptom itself; for example, its lending
      feasibility to the patient's alternative career by making of it something less
      ideal and therefore less crucial than it otherwise would have been. Moreover, the
      harrowing consumption of time that characterises such symptoms was also
      maintaining a state of moral masochism that gratified the patient's subdued
      ambivalence towards the analyst and the analysis. A literary project that exists
      principally to serve such ends as these expires as something feasible when the
      analysis has subtracted from it its extra-literary aims and devices.

PMID- 7628898
TI  - The beneficial aspects of the patient-analyst match.
AB  - Attempts to define the central factors contributing to psychological change from
      psychoanalytic treatment have occurred throughout the history of psychoanalysis.
      Insight from interpretations and clarifications and the affective relationship to
      the analyst are agreed to be the crucial elements in analytic work as they play
      out in the transference and resistance. Each patient and analyst pair, however,
      has its own unique interaction. Even though patients potentially may have
      successful analyses with many different analysts, the experience of each patient
      analyst dyad has its own non-replicable characteristics. The interdigitation of
      the particular characteristics of the analyst and the patient may be
      therapeutically beneficial and may determine the depth and range of work in any
      specific area. An illustration is offered where the positive impact of an
      interaction came from subtle, often non-verbal aspects of a particular patient
      analyst pair. The author's thesis is that, in addition to the analyst's technical
      and empathic skill, the subtle aspects of character and conflict of both patient
      and analyst and their interplay constitutes a central therapeutic factor in
      analytic work.

PMID- 7628899
TI  - The role of the father in a pre-suicide state.
AB  - In the self-examination that followed a patient's suicide attempt, the author was
      worried by three features which he had observed in an earlier suicide attempt by
      another patient: (1) the father had not featured in the analysis as much as would
      have been expected, (2) the suicide attempt occurred during a period when the
      time and place boundaries of the analytic setting were in jeopardy, e.g. the
      patient was absent from sessions; and (3) this coincided with the author having
      temporarily underestimated the suicidal risk. These three features were
      illuminated by a transference to a father who did not claim his child for himself
      and offer an alternative to fusion with a dangerous mother. Although the
      patient's suicide fantasies were based on a pathological bond with his mother,
      during the pre-suicide state the internalised father who had failed to protect
      his son from mother was evoked in the countertransference to function as a
      sanction for the suicidal act.

PMID- 7628900
TI  - A surrogate carries a fertilised ovum: multiple crossings in ego boundaries.
AB  - Recent advances in reproductive technologies have created situations in which
      early psychoanalytic thinking with regard to the procreative wish, infertility,
      and the significance of pregnancy in mothering, calls for reconsideration. The
      paper addresses briefly issues related to psychological infertility; it focuses
      specifically on possible psychological implications during full surrogacy, as
      this procedure is now practised in many fertility clinics in North America. The
      analysis of a young woman whose infertility was related to her exposure, during
      intra-uterinary life, to her mother's hormonal treatment (DES), presented us with
      the opportunity to observe the many psychological issues developing during in
      vitro fertilisation (IVF) and other similar procedures and, ultimately, to
      address the far more complex interpersonal states evolving between the biological
      (genetic) mother and the surrogate during full surrogacy. Analytic material
      provides the opportunity to discuss, specifically, questions of boundaries and
      boundary confusion in the relationship between the surrogate (who carried the
      couple's fertilised ovum to the birth of a healthy child) and the genetic mother.

PMID- 7628901
TI  - Analytic listening and the analyst's self-analysis.
AB  - In recent decades analysts in North America have been writing about the challenge
      of listening to clinical material in ways which take account of the two person
      psychoanalytic situation. In that mutually regressive setting, self-analytic
      thinking on behalf of the analysand is essential for many analysts, because in it
      the analyst often relies on thoughts and feelings about conflicted and painful
      personal experience better to understand the analysand's inner experience.
      Effortful introspection allows some mastery, at least for the moment, of conflict
      which might otherwise prevent the analyst from thinking about and understanding
      what his inner experience may be telling him about his patient's mental life. In
      this essay the author describes the way an humiliating memory from his own
      childhood, recalled in response to his patient's dream, served as a cornerstone
      of his self-analytic effort on behalf of his patient. Coupled with self-analysis
      concerning his recent neck surgery, the analyst's self-reflections allowed him to
      be sensitive to a critical development in the analysis. This way of working
      complements the more traditional way analysts develop ideas from direct
      observation of the analysand in the consulting room.

PMID- 7628902
TI  - The analytic process: clinical and research definitions.
AB  - Though analytic process is a core concept in psychoanalysis, no consensus
      definition or reliable method of assessment currently exists. This paper reviews
      clinical definitions of analytic process and concludes that analytic process is
      comprised of free association, resistance, interpretation and working through.
      Psychoanalytic outcome research suggests that analytic process develops in only
      40 per cent of analyses. Though the presence of analytic process is highly
      correlated with therapeutic benefit, significant numbers of analytic patients (50
      per cent) achieve good outcome despite the fact that an analytic process never
      developed in treatment. A review of process research on the components of
      analytic process suggests that a variety of measures already exist for free
      association, resistance, and interpretation. As in the clinical literature,
      working through is less well defined and studied. Although several researchers
      have assessed analytic process using a variety of techniques, these clinically
      defined component measures of analytic process have not yet been synthesised into
      a comprehensive scale. Such a measure of analytic process would have the benefit
      of being easily applied to an adequate sampling of session material and would
      result in a judgement about the presence and quality of analytic process. A
      consensus definition and the development of a reliable method to assess analytic
      process will be of use in clinical, educational and research settings as well as
      in attempts to define and quantify psychoanalytic treatment.

PMID- 7628903
TI  - Common ground, uncommon methods.
AB  - The author, an American-trained psychoanalyst, currently a member of a
      theoretically heterogeneous European psychoanalytic society, reflects on his
      experiences with the different types of analysis practised in continental Europe
      and in the United States. Sharing some 'common ground' assumptions does not mean
      that analysts worldwide use comparable clinical methodology. Practitioners from
      disparate schools differ not only in their metatheoretical frameworks, but also
      in their theories of technique. Differences in clinical methods affect the
      scientific quality of clinical researches and, probably, influence therapeutic
      outcome. The lack of commonality in psychoanalytic methods often seems related to
      the disparate uses of logical fallacies in clinical reasoning; this, in turn, may
      be a consequence of socio-historical determinants. Several discussions of one
      clinical presentation are supplied as an illustration. It is suggested that
      efforts be made to further examine the relative validity of disparate inference
      making models, and the practical results of applying different clinical methods.

PMID- 7628905
TI  - Merton Max Gill (1914-1994).

PMID- 7628904
TI  - Constitutive signifiers or fetishes in Shakespeare's the Merchant of Venice?
AB  - Assessments of psychodynamic structures and processes implicit in 'The Merchant
      of Venice' vary considerably according to whether Lacanian or object-relations
      tenets are applied. Aspects of the play resemble a pattern described in Lacan's
      seminar on E. A. Poe's story 'The purloined letter': the 'itinerary' of the
      'signifier' represented by a roving letter in Poe's story closely matches in
      outline the adventures surrounding roving rings in Shakespeare's play. Using
      Poe's story as evidence, Lacan's seminar argues that human identity is a product
      of 'signifiers', and not vice-versa. This conclusion that human subjectivities
      are constituted by signifiers does not stand up well in relation to the power of
      the rings and other signifying physical objects appearing in Shakespeare's play
      and its source stories. Recently expanded understandings of Freud's ideas about
      fetishism better explain the often malevolent power of the play's many signifying
      physical objects. In these the essential potential for damage is to sound
      personal relations with inner and outer objects of love. Explanations emphasising
      that distorted object relations and damaged subjectivities may be redeemed accord
      well with the dramatic and poetic patterns of Shakespeare's play, indicating that
      it, while portraying painful dilemmas, is still a comedy.

PMID- 7628906
TI  - In Vienna veritas.

PMID- 7628907
TI  - Functional magnetic resonance imaging of primary visual processing using a 1.0
      Tesla scanner.
AB  - Recent advances in functional magnetic resonance imaging (fMRI) at > or = 1.5 T
      magnetic field strength and with high speed single-shot echo planar imaging
      techniques have made it possible to monitor local changes in cerebral blood
      volume, cerebral blood flow, and blood oxygenation level in response to sensory
      stimulation, simple motor activity, and possibly also to more complex cognitive
      processing. However, fMRI has also been accomplished on conventional MR scanners
      of medium field strength (approximately 1.0 T) using special pulse sequences and
      appropriate methods for image analysis. We present results from six subjects on
      photic stimulation using a standard 1.0 T MR scanner together with special
      software for off-line image analysis. Continuous serial T2-weighted imaging were
      performed for 6 minutes in the plane of the calcarine fissure. There were 3
      repetitions of 1 minute resting state of darkness (OFF) and 1 minute activated
      state (ON) with 8 Hz flicker stimulation. To directly map these functional images
      to the underlying anatomy we also acquired a high resolution T1-weighted image
      from the same axial slice. The results demonstrated that stimulus-related signals
      can be obtained from primary visual cortex with a conventional 1.0 T MR scanner.
      Further methodological improvements are discussed and related to present and
      future possibilities for the use of fMRI within psychophysiology.

PMID- 7628908
TI  - Startle responses of spider phobics to masked stimuli: a pilot study.
AB  - The present study tested the hypothesis that briefly flashed and backwardly
      masked phobic stimuli potentiate startle reflexes in phobic subjects. Spider
      phobic (n = 17) and normal control (n = 12) subjects were exposed to short (30
      ms) and backwardly masked presentations of phobic slides (i.e., spiders) and
      neutral slides (i.e., flowers, mushrooms, snakes). On half the trials, eyeblink
      startle reflexes were elicited with auditory probes following presentation of the
      slides. In spite of the degraded stimulus conditions, there were some indications
      that phobics exhibited a startle pattern different from control subjects. More
      specifically, phobic subjects tended to react with larger startles during the
      second block of spider trials than control subjects. No such group differences
      were found for the neutral trials. As the eyeblink startle reflex is closely
      linked to the thalamo-amygdala pathway, the present findings provide some
      preliminary support for the idea that the preattentive processing of phobic cues
      is located at the subcortical level.

PMID- 7628909
TI  - Impairments of the response preparation process in the elderly.
AB  - In 20 young adults (23.1 +/- 1.64 yrs) and 20 old adults (68.5 +/- 5.53 yrs), H
      reflexes were evoked simultaneously in the right soleus muscle that was preparing
      to respond to a reaction time stimulus and in the left soleus muscle that was
      uninvolved in the impending reaction time response. In the one-second period
      preceding the presentation of the response stimulus, the right H-reflex was
      inhibited as compared to the left H-reflex in the young adults; whereas, in the
      old adults, the response preparation profiles for the left and right H-reflexes
      were similar. Following the presentation of the response stimulus, H-reflex
      facilitation in the young adults reflected a non-specific tuning response and a
      specific, movement-related response. The nonspecific H-reflex enhancement was not
      observed in our older adults. These results indicate that the generalized tuning
      sequence necessary for movement planning is impaired in the elderly.

PMID- 7628910
TI  - Intrathecal pertussis toxin but not cyclic AMP blocks kappa opioid-induced
      antinociception in rat.
AB  - The role of inhibitory G-proteins and cyclic AMP in spinal mechanisms of kappa
      opioid receptor-mediated antinociception was assayed by recording the withdrawal
      response latency of the rat tail following immersion into a water bath of 49
      degrees C. Intrathecal administration of pertussis toxin (1 microgram/rat, five
      days before the behavioral evaluation) prevented the antinociceptive effect of
      the kappa receptor agonist U-50,488H, while administration of dibutyryl cyclic
      AMP (10 micrograms/rat, 17 min. after U-50,488H) did not antagonize the
      antinociceptive action of the kappa ligand. Results suggest that in the spinal
      cord the signal transduction mechanism subserving the antinociceptive effect of U
      50,488H involves a Gi or Go protein, but also that cyclic AMP is not implicated
      in coupling Gi/Go proteins to the effector system.

PMID- 7628911
TI  - Improvement of right hemispheric functions in a child with Gilles de la
      Tourette's syndrome by weak electromagnetic fields.
AB  - Gilles de la Tourette's syndrome (GTS) is a chronic, familial neuropsychiatric
      disorder of unknown etiology characterized clinically by the occurrence of motor
      and vocal tics and by the presence of a variety of neurobehavioral and
      neurocognitive abnormalities including hyperactivity, self-multilatory behavior,
      obsessive-compulsive behavior, learning disabilities, and conduct disorder. On
      the basis of neuropsychological assessments it has been suggested that GTS is
      associated with greater right than left hemispheric dysfunction which accounts
      for decrements in visuospatial, visuoconstructional and visuomotor skills in
      these patients. Recent case studies have demonstrated that extracranial
      application of electromagnetic fields (EMFs) in the picotesla (pT) range
      intensity improves visuospatial and visuoperceptive functions in patients with
      neurodegenerative disorders including Parkinson's disease, multiple sclerosis and
      Alzheimer's disease. I now present a 6 1/2 year old boy with GTS in whom this
      treatment modality produced, in addition to symptomatic behavioral improvement,
      also improvement in visuoconstructional and visuomotor skills as evidenced on
      various drawing tasks particularly copy of the Rey-Osterrieth Complex Figure, a
      task which is especially vulnerable to right hemispheric functions. These
      findings suggest that pT range EMFs may be useful for the treatment of GTS and
      related disorders and also reverse some of the cognitive impairments associated
      with the disease which are related to right hemispheric dysfunction and which
      contribute to learning disabilities in these patients.

PMID- 7628912
TI  - Resolution of Lhermitte's sign in multiple sclerosis by treatment with weak
      electromagnetic fields.
AB  - Lhermitte's sign, the occurrence of an electrical sensation passing down the back
      to the legs on flexion of the neck is a common and characteristic feature of
      multiple sclerosis (MS) which is related to spinal cord lesions affecting the
      posterior columns and cervical nerve roots. The Lhermitte's sign, which has been
      reported to occur at some time in up to 25% of MS patients, is seldom painful but
      is often a cause of distress to the patient and usually a marker of increased
      disease activity. Treatment with extracranial picotesla range pulsed
      electromagnetic fields (EMFs) has been found efficacious in the management of
      various MS symptoms including pain syndromes. The present communication concerns
      three MS patients in whom two brief applications of EMFs resulted in resolution
      of the Lhermitte's sign which emerged during a period of exacerbation of symptoms
      in one patient and during a prolonged phase of symptom deterioration in the other
      two patients. As the cause of the Lhermitte's sign is thought to result from the
      spread of ectopic excitation in demyelinated plaques in the cervical and thoracic
      regions of the spinal cord, it is hypothesized that the effects of EMFs are
      related to the reduction of axonal excitability via a mechanism involving changes
      in ionic membrane permeability. A systemic effect on pain control systems is also
      postulated to occur secondary to the effects of EMFs on neurotransmitter activity
      and pineal melatonin functions. This report underscores the efficacy of picotesla
      EMFs in the management of paroxysmal pain symptoms in MS.

PMID- 7628913
TI  - 12th International Australasian Winter Conference on Brain Research. Queenstown,
      New Zealand, August 1994. Abstracts.

PMID- 7628914
TI  - The topography of event-related potentials in passive and active conditions of a
      3-tone auditory oddball test.
AB  - Normalized event-related potential (ERP) data were analysed for topographical
      differences of ERP amplitude or latency in two conditions of a 3-tone oddball
      paradigm. The aim was to compare perception-related features relating to tone
      type (passive non-task condition) with focussed attention-related features
      (active discrimination of target from non-target) in 5 ERP components from 23
      young healthy subjects. The tones used were a common standard (70%, 0.8 KHz), a
      deviant standard (15%, 2 KHz) and a 1.4 KHz tone (15%, t) also used as the target
      (T). A site x tone interaction was obtained for P1 amplitude (augmenting with
      pitch anterior to posterior). The opposite tendency was seen for P2 to the right
      of midline maxima. No interaction was obtained for N1 amplitude. Condition became
      relevant for the N2-P3 complex. Frontal N2 amplitude increased after rare tones
      in the active condition. Posterior P3 peak size distinguished between tone (more
      widespread response to the common tone) and condition (more right-sided in the
      passive condition). The common tone elicited more widespread shift to the right
      than the rare tones. Latency was affected by condition from the P2 onwards and
      confirmed many of the amplitude interactions. This report extends and qualifies
      well-known main effects of tone and condition through main site effects to
      lateral sites. It supports claims of multiple sources of ERP components, except
      for N1 and P2. The contributions of these sources are influenced by tone-features
      (from P1) and the presence or absence of focussed attention (from the N2-P3
      complex).

PMID- 7628915
TI  - The topography of 4 subtraction ERP-waveforms derived from a 3-tone auditory
      oddball task in healthy young adults.
AB  - Five components were studied in 4 subtraction waveforms derived from ERPs
      obtained in passive and active conditions of a 3-tone oddball task (common = 70%,
      C, 0.8 KHz; deviant = 15%, D, 2 KHz; 1.4 KHz = 15%, t, also used as a target
      (T)). These waveforms reflect different stimulus-mismatch processes and thus
      their topography could be revealing of different brain regions mediating them.
      The following mismatches were studied: stimulus-mismatch (deviant--common, D/C,
      rarity and pitch confounded), pitch-mismatch (T--deviant, T/D, rarity not target
      features controlled), attention-mismatch (T-t), T/t, controlled for pitch and
      rarity to show the influence of target features). These are compared with
      Goodin's procedure [G-wv, (T--common (active))--(t--common (passive))]. There
      were main site effects in normalized data in all cases (not P2 and N2 latency).
      There were separate frontal and posterior contributions to P1, with the former
      emphasized where target comparisons were involved. Frontal N1 peaks, largest in
      D/C, spread posterior and to the right where target matching was involved. P2
      posterior maxima were also less localized where target features were involved in
      the comparison. N2 topography was similar between waveforms but spread slightly
      more to each side in the T/t comparison. Onset was earlier in the D/C comparison.
      Parietal P3 peaks in waves based on target-ERPs showed a left temporal shift (vs
      D/C), though in T/D P3 was in fact maximal on the right. Thus an attentional
      effect is evident as early as 60 ms. Target features modify the anteroposterior
      distribution of positivity and negativity for the early components and in the
      lateralization of P3-like positivity. A comparison of waveforms by latency of
      potential shift (running t-test) vs peak identification (MANOVA) is illustrated
      and discussed. D/C and T/t (rather than T/D or G-wv) waveforms are recommended
      for distinguishing comparator mechanisms for stimulus- and task-relevant
      features.

PMID- 7628916
TI  - Immunosuppressive and antiproliferative effects of somatostatin analog SMS 201
      995.
AB  - The effects of long acting somatostatin analog SMS 201-995 were examined in vivo
      on: 1) lymphoid morphostasis and functional reactivity of cells obtained from SMS
      treated donors, 2) on humoral, and 3) cellular type of immunity; and in vitro on:
      1) blastic transformation of lymphocytes stimulated by activators of different
      transmembrane pathways (CD2 by PHA and CD3/TCR by anti-CD3 monoclonal antibody
      and by allogeneic cells) and 2) on growth and secretory activity of several
      hybridoma cell lines. The data have shown that SMS in vivo decreases the
      proportion of CD4+, CD5+ and Ig+ cells in spleen. The reactivity of these cells
      to Con A was suppressed, but their spontaneous blastic transformation was
      increased. SMS suppressed also the plaque forming cells generation and
      proliferation of cells in popliteal lymph nodes during the local host versus
      graft reaction. The former immunosuppression was abrogated with the use of growth
      hormone, while in the latter, the time dependent changes in spleen composition
      were also noticed. The data obtained in vitro revealed that SMS may inhibit only
      the CD2-induced blastogenesis (in early and late interval after the use of PHA).
      SMS inhibited also the spontaneous growth and/or secretion of antibodies in some
      hybridoma cell lines.

PMID- 7628917
TI  - The role of geriatrics in medical education at the University of Hawaii.

PMID- 7628918
TI  - From prontolyn to biaxin: the half-century of antibiotics.

PMID- 7628919
TI  - The physician as patient: the thallium treadmill stress test.

PMID- 7628920
TI  - The role of the medical home and interprofessional collaboration.
AB  - The medical home plays a critical role on the interprofessional team to improve
      school readiness of children before they enter primary school. School readiness
      and optimal health require a combination of medical care with health and social
      services both to prevent and to improve the effects of negative conditions.
      Hawaii Medical Association has two new projects aimed toward that end.

PMID- 7628922
TI  - Food on the hoof: stamping out food safety concerns.

PMID- 7628921
TI  - Outcome-oriented quality assurance in an ambulatory setting.
AB  - Quality assurance has become an increasing concern to the government, health care
      plans, and organized medicine as managed care systems reduce absolute dollars
      spent on care. Most small group practices and individual physicians have little
      control over the various methods used to evaluate the quality of care. A
      computerized quality management approach improves quality assessment and directs
      local changes to improve patient care.

PMID- 7628923
TI  - Endangered species and the veterinary practitioner.

PMID- 7628924
TI  - FSIS explains benefits of HACCP.

PMID- 7628925
TI  - Workshop challenges veterinary community to address substance abuse.

PMID- 7628926
TI  - More on food safety considerations.

PMID- 7628927
TI  - What is your diagnosis? Radiographic diagnosis--the talocalcaneal joint is
      luxated, and multiply small chips are evident cranial to the calcaneus.

PMID- 7628928
TI  - Animal behavior case of the month. Aggression between 2 pugs in a household.

PMID- 7628929
TI  - Veterinarians and waste disposal.

PMID- 7628930
TI  - Gastric dilatation-volvulus after splenic torsion in two dogs.
AB  - Two dogs developed gastric dilatation-volvulus 2 and 17 months, respectively,
      after splenectomy for treatment of splenic torsion. Splenic displacement and
      torsion may stretch the gastric ligaments, allowing increased mobility of the
      stomach. After splenectomy, an anatomic void may be created in the cranioventral
      part of the abdomen, contributing to the mobility of the stomach. Veterinarians
      treating dogs with isolated splenic torsion may wish to consider prophylactic
      gastropexy at splenectomy, to reduce the chance of future gastric dilatation
      volvulus. Prophylactic gastropexy should be done only if the dog's hemodynamic
      status is stable enough to allow for performance of the additional surgery.

PMID- 7628931
TI  - Yersinia pestis infection in three dogs.
AB  - Yersinia pestis infection was diagnosed in 3 dogs. Clinical signs included
      lethargy (3 dogs), pyrexia (2 dogs), and a purulent skin lesion in the cervical
      region (2 dogs). Yersinia pestis infection is a potentially fatal zoonotic
      disease of human beings. Human cases have resulted from contact with infected
      domestic cats; however, the risk of human infection from contact with infected
      domestic dogs is unknown. Dogs frequently are exposed to Y pestis in areas in
      which there are plague epizootics; however, clinical illness in dogs is rare. In
      the western United States, where Yersinia pestis is endemic, plague should be
      considered in the differential diagnosis when examining dogs with nonspecific
      fever and lethargy.

PMID- 7628932
TI  - Pneumocystectomy in a Midas cichlid.
AB  - A pet Midas cichlid with a 2-year history of a distended abdomen and inadequate
      buoyancy control was found, radiographically, to have an abnormally large swim
      bladder. A recirculating anesthesic machine was constructed, and the fish was
      anesthetized with tricaine methanesulfonate prior to removing a portion of the
      swim bladder. The entire procedure lasted 71 minutes. Buoyancy problems in pet
      fishes are common. Causes include subcutaneous air accumulation, infectious
      disease of the swim bladder inner ear disease, and gastroenteritis. Reduction of
      the volume of the swim bladder improved this fish's ability to maintain a normal
      posture in the aquarium.

PMID- 7628933
TI  - Pheochromocytoma and hyperadrenocorticism in dogs: six cases (1982-1992).
AB  - Pheochromocytoma was diagnosed in 4 dogs with pituitary-dependent
      hyperadrenocorticism and 2 dogs with hyperadrenocorticism caused by
      adrenocortical tumor. All dogs were examined initially because of clinical signs
      associated with hyperadrenocorticism. Pheochromocytoma was suspected in 2 dogs
      with pituitary-dependent hyperadrenocorticism that had ultrasonographic evidence
      of an adrenal gland mass, and in 1 dog suspected to have hyperadrenocorticism
      associated with an adrenocortical tumor after complications (systemic
      hypertension, cardiac arrhythmias) developed during induction of anesthesia.
      Pheochromocytoma was an unexpected finding at necropsy in the remaining 3 dogs.
      Two dogs collapsed suddenly and died before diagnostic tests could be performed;
      the other dog died during anesthesia for cobalt teletherapy of a pituitary
      macroadenoma. Hypertension, most notable during digital manipulation of the
      affected adrenal gland, developed during anesthesia and surgery in 3 dogs that
      underwent exploratory celiotomy.

PMID- 7628934
TI  - Case-control study of risk factors for development of pleuropneumonia in horses.
AB  - Risk factors for development of pleuropneumonia were determined by reviewing
      medical records of 45 horses with pleuropneumonia and 180 control horses examined
      between Jan 1, 1980 and Jan 1, 1990. Factors considered included age, breed, sex,
      occupation, transport farther than 500 miles within the previous week, racing
      within the previous 48 hours, viral respiratory tract infection or exposure to
      horses with viral respiratory tract disease within the previous 2 weeks, and
      vaccination against influenza or rhinopneumonitis within the previous 6 months.
      Results indicated that Thoroughbreds were at a greater risk of developing
      pleuropneumonia than were other horses, and Standardbreds were at a reduced risk.
      Transport farther than 500 miles and viral respiratory tract disease or exposure
      to horses with respiratory tract disease were determined to be risk factors for
      the development of pleuropneumonia.

PMID- 7628935
TI  - Uterine torsion associated with small intestinal incarceration in a mare at 126
      days of gestation.
AB  - A mare at 126 days of gestation was examined because of signs of abdominal pain.
      The cause of abdominal pain could not be determined by physical examination. Lack
      of response to analgesics and small intestinal distention on palpation per rectum
      prompted exploratory celiotomy. Small intestine was found to be entrapped by the
      uterus, which had undergone torsion. The uterus was returned to its correct
      position, and the small intestine was decompressed. After surgery, the mare was
      treated with orally administered progestin to prevent abortion. The mare
      recovered and delivered a live foal at 354 days of gestation. Uterine torsion at
      such an early stage of gestation is not common in horses.

PMID- 7628936
TI  - Paraneoplastic bullous stomatitis in a horse.
AB  - An adult horse with a 2-month history of anorexia, ataxia, and oral blisters had
      developed these clinical signs just prior to the appearance and growth of a
      cervical mass. Bullous stomatitis was characterized histologically as
      subepidermal clefting. Clinical signs were unresponsive to treatment with
      antibiotics or corticosteroids; however, surgical removal of the mass coincided
      with remission of all signs. Histologic findings of the mass were consistent with
      hemangiosarcoma. Results of indirect immunofluorescence and immunoprecipitation
      on frozen serum from the horse were characteristic of paraneoplastic pemphigus in
      human beings, a newly recognized mucocutaneous autoimmune disease associated with
      neoplasia.

PMID- 7628937
TI  - Ventricular tachycardia associated with exhaustive exercise in a horse.
AB  - Ventricular tachycardia was diagnosed in a 12-year-old unconditioned Appaloosa
      gelding after a 3-day trail ride. Initial signs were those of abdominal
      discomfort, ileus, and dehydration. Medical treatment included IV administration
      of lactated Ringer's solution. During hospitalization, the horse developed
      ventricular tachycardia. Serum potassium concentrations were within reference
      limits; however, assessment of total body potassium stores was not performed.
      Resolution of the arrhythmia occurred with further fluid treatment and potassium
      supplementation. Cardiac arrhythmias should be considered in horses in which
      fluid and electrolyte disturbances are evident after exhaustive exercise.

PMID- 7628938
TI  - Repair of a full-thickness gastric rupture in a horse.
AB  - A 14-year-old Thoroughbred broodmare was evaluated for signs of mild to moderate
      abdominal pain of 5 hours' duration. Exploratory celiotomy revealed a 20 x 8-cm
      subserosal hematoma associated with a focal serosal perforation overlying a
      muscular tear along the parietal surface of the stomach. The odor of intestinal
      tract gas was detected, but gross contamination of the abdomen was not evident.
      Concurrent partial volvulus of the small intestine was evident. Removal of the
      large colon from the abdomen appeared to coincide with propagation of the serosal
      perforation to a full-thickness gastric rent. The tear was repaired by use of a 2
      layer inverting closure. The horse had evidence of an acute gastrointestinal
      tract hemorrhage 10 days after surgery, but responded to treatment. At a 2-year
      follow-up evaluation, the mare had foaled once and had not experienced recurrent
      signs of abdominal disease.

PMID- 7628939
TI  - Lead arsenate poisoning in a herd of beef cattle.
AB  - Lead arsenate poisoning was diagnosed in 2 beef heifers and was suspected in 6
      other cattle from the same herd that had died previously and were not examined.
      Clinical signs in affected cattle included staggering, dehydration, hemorrhage,
      acidemia, and shock. Diagnosis was by arsenic and lead analysis of urine samples
      and kidney and liver tissue digests. Both examined heifers died within 4 days of
      onset of clinical signs. These cattle had been moved from an area with poor
      grazing conditions to a pasture with abundant forage. This pasture had an open
      shed that contained an open sack of lead arsenate insecticide. Old stores of this
      inorganic insecticide may still exist on farms or ranches, and are a hazard to
      livestock.

PMID- 7628940
TI  - Tourniquet-induced hypertension in an ostrich.
AB  - Surgery was performed on a 3-year-old 110-kg male ostrich (Struthio camelus) to
      remove a sequestrum from the dorsal aspect of the left tarsometatarsal bone. A
      pneumatic tourniquet was positioned proximal to the surgical site and inflated to
      600 mm of Hg. Systolic blood pressure increased 35% over 105 minutes while the
      tourniquet was inflated. Systolic blood pressure decreased 31.5% within 30
      seconds after removal of the tourniquet pressure. Recovery from anesthesia and
      surgery was routine. The tourniquet-induced hypertension in this ostrich was
      similar to that reported for human beings and horses.

PMID- 7628941
TI  - National survey on veterinarian-initiated drug use in lactating dairy cows.

PMID- 7628942
TI  - Estimation of non-additive genetic variances in three synthetic lines of beef
      cattle using an animal model.
AB  - Dominance and additive x additive genetic variances were estimated for birth and
      weaning traits of calves from three synthetic lines of beef cattle differing in
      mature size. Data consisted of 3,992 and 2,877 records from lines of small-,
      medium-, and large-framed calves in each of two research herds located at Rhodes
      and McNay, IA, respectively. Variance components were estimated separately by
      herd and line for birth weight (BWT), birth hip height (BH), 205-d weight (WW),
      and 205-d hip height (WH) by derivative-free REML with an animal model. Model 1
      included fixed effects of year, sex, and age of dam. Random effects were additive
      direct (a) and additive maternal (m) genetic with covariance (a,m), maternal
      permanent environmental, and residual. Model 2 also included dominance (d) and
      model 3 included dominance plus additive x additive (a:a) effects. In general,
      only slight changes occurred in other variance components estimates when day was
      included in Model 2. However, large estimates of additive x additive genetic
      variances obtained with Model 3 for 4 out of 24 analyses were associated with
      reductions in estimates of direct additive variances. Direct (maternal)
      heritability estimates averaged across herd-line combinations with Model 2 were
      .53(.11), .42(.04), .27(.12), and .35(.04) for BWT, BH, WW, and WH, respectively.
      Corresponding covariance (a,m) estimates as fractions of phenotypic variance
      (sigma p2) were .00, .01, .01, and .06, respectively. For maternal permanent
      environmental effects in Model 2, average estimates of variances as fractions of
      sigma p2 across herd-line combinations were .03, .00, .05, and .02, for BW, BH,
      WW, and WH, respectively. Dominance effects explained, on average, 18, 26, 28,
      and 11% of total variance for BWT, BH, WW, and WH, respectively. Most of the
      estimates for additive x additive variances were negligible, except for one data
      set for BWT, two for BH, and one for WH, where the relative estimates of this
      component were high (.21 to .45). These results suggest that most of the non
      additive genetic variance in the traits studied is accounted for by dominance
      genetic effects.

PMID- 7628943
TI  - Mortality of domestic sheep in free-ranging flocks in southeastern Norway.
AB  - Lamb mortality during three summer grazing seasons (1988 to 1990) among 1,399
      lambs in three flocks of free-ranging domestic sheep in southeastern Norway was
      modeled using logistic regression. Ewe mortality during the same three seasons
      among the 295 ewes in one of the three flocks was also modeled. During the
      period, mortality among the 1,399 lambs and 295 ewes was 7.2% and 12.5%,
      respectively. Other work has shown predation by brown bears to be the single most
      important mortality factor in all three flocks, especially among ewes. Year,
      herd, sex, age of dam, and spring growth rate (i.e., from birth to release onto
      summer range) were statistically significant (P < or = .05) in explaining
      mortality among lambs. Lamb mortality was higher in 1989 and 1990, higher in
      HerdA (the most isolated herd that grazed adjacent to the Swedish border), higher
      among lambs of yearlings, among male lambs, and among lambs with low spring
      growth rate. Ewe mortality increased with age (P = .07). Adjustment of age for
      weight weakened the statistical association between age and mortality, however (P
      = .16). The negative association between lamb mortality and age of dam and the
      positive association between ewe mortality and ewe age may both be related to the
      quality of maternal care provided by ewes of different ages. Subsequently,
      attempts to compensate for losses, especially those due to predation by bears,
      lead to a younger herd that may increase the herd's overall vulnerability.

PMID- 7628944
TI  - Comparison of daily versus continuous administration of somatotropin on growth
      rate, feed intake, and body composition in intact female rats.
AB  - The response to continuous delivery or daily bolus injection of porcine
      somatotropin (pST) was compared in mature, pituitary-intact female rats (225 g).
      Growth rate in control rats was approximately 1 g/d over the 14-d study. There
      was a dose-dependent (0, .4, 1.2, and 3.6 mg of pST/d; P < .001) increase in rate
      of gain with an interaction (P < .001) of dose and mode of delivery. The slope of
      the dose-response curve for growth rate was linear on a logarithmic scale for
      both modes of delivery but was greater for continuous delivery. At the low dose
      (.4 mg/d) pST stimulated gain (21.7 g/14 d above control, P < .05) when
      administered by daily injection but failed to stimulate gain (6.0 g/14 d above
      control, NS) when delivered continuously. At the high dose (3.6 mg/d), gain
      (above that in control rats) was 49.1 and 79.7 g/14 d for daily and continuous
      delivery; the two modes were different (P < .05) from each other. Feed intake and
      liver weights were also stimulated by pST in a dose-dependent manner. The
      increase in liver size was accompanied by a dose-dependent increase in liver DNA,
      indicative of an increase in cell number. Increased carcass gain was largely
      accounted for by increased carcass protein accretion. Rates of carcass lipid
      accretion were lower than those for protein accretion and were further decreased
      by pST, particularly by the high dose administered by continuous delivery, where
      a negative lipid accretion value was observed. Circulating IGF-I was increased by
      pST (P < .001) but was not affected by the mode of delivery. The results
      demonstrate that the increased gain observed in mature rats is largely due to
      lean tissue accretion and is accompanied by an increase in feed intake.

PMID- 7628945
TI  - Relationships among heat production, body weight, and age in Suffolk and Texel
      ewes.
AB  - The objective of this study was to test the null hypothesis that heat production
      (HP) was equivalent between Suffolk and Texel ewes at common fasted BW and at
      common ages. Open-circuit respiration calorimetry was used to estimate HP in 48
      Suffolk and 48 Texel ewes at eight ages (10, 15, 20, and 28 wk of age and 1.5,
      2.5, 3.5, and 4.5 yr of age). Sheep were individually penned in an
      environmentally controlled building 6 to 10 d before sample collection. Feed was
      removed 55 h before sample collection. Heat production measurements were made
      from 55 and 71 h of the feed restriction. Suffolk ewes had greater mature weights
      (P < .01) and reached maturity more rapidly than Texel ewes (P < .05). At a
      common weight, Texel ewes had a lower HP than Suffolk ewes. The ratio of HP:BW
      declined as ewes aged, as indicated by the fact that the slope of the log
      transformed data was negative and less than 1 (P < .01). The models predict that
      Suffolk ewes had a lower HP:BW than Texel ewes at a common age, but when ewes
      were compared at common proportions of mature weight HP:BW did not differ between
      breeds. Breed differences in HP seem to be the result of differences between
      breeds in maturing rate.

PMID- 7628946
TI  - Comparative effectiveness of somatotropin and anabolic steroids in feedlot
      steers.
AB  - Crossbred steers (n = 252, BW = 379 +/- 28 kg) were allotted to 42 pens in a 2 x
      3 factorial arrangement of treatments: control or steroid implant (STR; estradiol
      benzoate+progesterone [three lighter blocks reimplanted on d 84] and trenbolone
      acetate [reimplanted on d 63]), and either 0, 80, or 160 mg/wk of recombinant
      bovine somatotropin (bST). Steers were adapted to the finishing diet (12%
      roughage equivalent, 13% CP) before the start of the experiment and fed for 84 or
      119 d. Blood samples were taken on d 0, 14, 28, 56, and 84 for plasma urea N
      (PUN), serum somatotropin (ST), plasma insulin-like growth factor I (IGF-I), and
      plasma amino acid assay. Few interactions were noted (P > .1). Gain was increased
      by both treatments: 1.30 vs 1.66 kg/d for control vs. STR (P < .001) and 1.44,
      1.49, and 1.51 kg/d (linear, P = .07) for 0, 80, and 160 mg of bST/wk,
      respectively. Gain efficiency was also improved: 169 vs 205 g/kg (P < .001) and
      177, 189, and 195 g/kg (linear, P < .001), respectively. Average PUN was
      decreased (P < .001) 29% by STR and decreased 17 and 29% by 80 and 160 mg of
      bST/wk, respectively (linear, P < .001). Somatotropin decreased mean serum ST
      compared with controls; STR increased ST 36% compared with controls. Average
      plasma IGF-I was increased (P < .001) 12% by STR and 13 and 19% (linear, P <
      .001) by 80 and 160 mg of bST/wk, respectively. Both STR and bST influenced (P <
      .05) plasma amino acid profiles. Indicators of carcass fatness were decreased
      linearly (P < .05) by bST; STR implant tended to decrease carcass fatness and
      increase longissimus muscle area, which was related to carcass weight. The
      anabolic effects of STR and bST were found to be additive and possibly
      independent in feedlot steers.

PMID- 7628947
TI  - A comparison of preferences for pork sandwiches produced from animals with and
      without somatotropin administration.
AB  - Experimental auction markets were designed and used to investigate consumer
      preferences for sandwiches produced with meat from pigs treated with porcine
      somatotropin. A second-price, sealed-bid auction procedure was used to determine
      willingness to pay to exchange a pork loin sandwich with leaner meat from pigs
      treated with somatotropin for a similar sandwich with meat from untreated pigs.
      The research was conducted using a sample of 114 undergraduate students in Iowa,
      Arkansas, Massachusetts, and California. At the end of the experiment 33 of 58
      subjects would not bid to change their leaner pork for typical pork, whereas 15
      of 56 subjects would not bid to change their typical pork for leaner pork. The
      results suggest a preference for leaner meat from the treated pigs, but also the
      potential for niche markets for meat and meat products from untreated pigs.

PMID- 7628948
TI  - Effects of breed type and accelerated fat removal on subprimal yields and carcass
      values.
AB  - Nine Brown Swiss and nine English crossbred steers representing the industry
      standard were slaughtered to determine the effects of cattle type and hot fat
      removal on subprimal yields and carcass value. After dressing, cod fat, kidney,
      pelvic, and heart fat (KPHF), and subcutaneous fat thicker than .6 cm was removed
      from the right side of each carcass (HFT). The left side was not hot-fat trimmed
      (NFT). Both sides were fabricated into subprimal cuts with no more than .6 cm of
      subcutaneous fat. Carcass side values were adjusted to a 300-kg chilled carcass
      weight basis. All comparisons were made for the carcasses using a USDA Select
      quality grade end point. English crossbred steer carcasses had more (P < .05)
      subcutaneous fat on the loin and chuck and more (P < .05) total hot fat trim,
      when KPHF was not included, than Brown Swiss steers (P < .05). Brown Swiss steers
      had more (P < .05) KPHF. Hot-fat trimmed sides had higher (P < .05) percentage
      yields from the chuck, brisket, foreshank, rib, plate, round primal cuts, and
      most of the subprimal cuts than NFT sides, but the primal loin percentage was
      higher (P < .05) in the NFT sides. The total subprimal cuts yield was
      approximately 5% higher for the HFT sides than for the NFT sides, and the total
      fat trim during fabrication was more than 6% less. When the value of the sides
      was calculated from unadjusted weights, the NFT sides were approximately $26.50
      more valuable than the HFT sides.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7628949
TI  - Effects of postmortem aging time, animal age, and sex on degradation of titin and
      nebulin in bovine longissimus muscle.
AB  - This study was conducted to determine degradation of the giant myofibrillar
      proteins titin and nebulin in postmortem aged beef, with known tenderness values,
      from animals differing in sex (steers vs bulls) and age (cows vs steers and
      bulls). Ten bulls and 10 steers (both groups were approximately 14 mo old) and 10
      cows (44 to 108 mo old) were slaughtered. Longissimus muscle samples were removed
      for determination of Warner-Bratzler shear force, sensory panel tenderness
      evaluation, and SDS-PAGE analysis at 3, 7, 14, and 28 d postmortem. The SDS-PAGE
      analysis of titin and nebulin revealed that titin often migrated as three closely
      spaced bands (T1, T1-2, T2, in increasing order of migration) in 3-d postmortem
      samples. With increasing time post-mortem, intact titin (T1) decreased and
      degraded titin (T2) increased in all samples. Within a class (i.e., steers,
      bulls, or cows) the rate of conversion of T1 to T2 was slower in the less-tender
      samples. The T1 to T2 conversion postmortem was slower in the intact males
      (bulls) than in the castrated males (steers). The T1 to T2 conversion postmortem
      also was slower in the older animals (cows) in comparison to the younger steers,
      but not in comparison to the younger bulls. Nebulin was degraded by 3 d
      postmortem in tender samples from steers, but some nebulin remained in the less
      tender 3-d samples from steers and in all of the 3-d samples from bulls and older
      animals (cows). Intact nebulin was absent in all 7-d samples, regardless of the
      class of animal. Our results suggest that titin and nebulin are degraded at
      faster rates in more tender beef samples within each of the three classes of
      animals examined. The rate of degradation seems to differ when sex and age
      classifications are compared.

PMID- 7628950
TI  - Technical note: detection and quantification of supplemental fungal beta
      glucanase activity in animal feed.
AB  - Selected hydrolytic enzymes are added to animal feeds in order to degrade
      specific antinutritional factors and(or) to increase availability of certain
      components of feedstuffs to the animal. A method is described that allows
      detection and quantification of beta-glucanase activity in complex feedstuffs.
      The method is based on radial diffusion of an enzyme-containing feed extract
      through an agar gel in which lichenan substrate (a relatively inexpensive glucan
      of mixed beta 1-->4 and beta 1-->3 linkages) has been dissolved. A linear
      relationship between the diameter of the zone of substrate hydrolyzed and the log
      of enzyme activity present was observed. The assay described is technically
      straightforward and requires no specialized equipment. At typical commercial
      inclusion levels (1 kg/t), the activity of a supplemental beta-glucanase, added
      to feed in a commercial mill was determined by averaging several measurements,
      with a precision of +/- 4%, variation between individual readings of +/- 11.3%
      (SD), and recovery of 109%. By using high-concentration feed extracts, the method
      was sensitive enough to detect background and(or) supplemental beta-glucanase
      activities as low as .05 kg/t supplement equivalent. This method allows
      consumers, producers, and regulatory authorities to measure the activity of beta
      glucanase in feed at commercial inclusion levels and, hence, study the effects of
      processes such as pelleting and extrusion on such supplements.

PMID- 7628951
TI  - True digestibility of amino acids and protein in pigs with 13C as a label to
      determine endogenous amino acid excretion.
AB  - The objective of this study was to determine whether differential labeling of 13C
      occurs in pigs fed diets with different 13C abundances and, if so, to use 13C as
      a label to determine true amino acid digestibility. Forty-eight pigs averaging
      10.5 kg BW were fed dietary treatments consisting of a corn-corn gluten meal
      crystalline amino acid diet (C-CGM) and a wheat-soybean meal diet (W-SBM). The
      13C abundance of the amino acid fraction (AAF) of the C-CGM and W-SBM diets
      averaged delta 13C -14.19 and -26.36/1000, respectively. Three pigs/treatment
      group were killed when groups averaged 10.5 (initial), 22.9, and 46.6 kg BW, and
      AAF of organs were analyzed for 13C abundance. Carbon 13 in empty body AAF
      increased (-18.14, -13.98, and -12.66/1000) with increasing body weight in pigs
      fed the C-CGM diet and decreased (-18.06, -22.78, and -24.76/1000) in pigs fed
      the W-SBM diet. Liver, small intestine, and longissimus muscle tissues showed
      similar trends. Each tissue had dietary treatment effects (P < .001) and dietary
      treatment x weight group (P < .001) interactions. Ten pigs averaging 55.0 kg BW
      from each treatment group were assigned to metabolism cages and fed at 0700 and
      1900. Six of these pigs from each treatment group were implanted with T-cannulas
      in the ileum and given a 17-d recovery period. At 1900 on d 0 of the collection
      phase, pigs were switched to the opposite diet that contained chromic
      oxide.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7628952
TI  - Dietary and plasma branched-chain amino acids in relation to tryptophan: effect
      on voluntary feed intake and lactation metabolism in the primiparous sow.
AB  - Seventy-six gravid gilts of different genotypes, Yorkshire x Duroc (YD) and Pig
      Improvement Company (PIC), were used in two trials to test the effect of
      decreasing the dietary ratio of tryptophan: branched-chain amino acids (BCAA) on
      feed intake, plasma metabolites, and body weight change during a 4-wk lactation
      period. The dietary ratio of tryptophan: BCAA was .063 in the Control and .041 in
      the experimental diet (BC). Gilts were fed 1.8 kg/d from d 107 of gestation until
      farrowing and given ad libitum access to feed during lactation. Feed consumption
      was measured daily. Body weights and preprandial blood samples were taken on d
      107 of gestation and on d 1, 7, 14, and 21 postpartum. Plasma glucose, NEFA, urea
      nitrogen, ammonia, N tau-methylhistidine, and alpha-amino nitrogen were measured.
      The plasma tryptophan:BCAA ratio was higher (P < .05) on d 1 postpartum than on d
      107 of gestation and d 7 postpartum in the Control group. Dietary addition of
      BCAA (BC) reduced (P < .06) the plasma tryptophan: BCAA ratio during the early
      postpartum period compared with the Control group but did not affect the other
      plasma metabolites measured. Feed intake was lower (P < .08) between d 6 and 12
      of lactation in sows fed the BC diet. Regression of d-1 plasma NEFA concentration
      on d-1 postpartum feed intake was significant (r2 = .41; P < .05). The PIC sows
      showed a tendency for positive lactation body weight response to the BC diet (P =
      .2), whereas the response of YD sows was not significant (P < .8).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7628953
TI  - The effect of excessive dietary vitamin A on performance and vitamin E status in
      swine fed diets varying in dietary vitamin E.
AB  - A study was conducted to evaluate the effects of high dietary vitamin A on
      vitamin E status and performance of growing-finishing pigs fed diets supplemented
      with varying levels of vitamin E. Treatments consisted of corn-soybean meal-based
      diets supplemented with retinyl acetate to provide 2,000 or 20,000 IU of vitamin
      A/kg of diet and with DL-alpha-tocopheryl acetate to provide 0, 15, or 150 IU of
      added vitamin E/kg in a 2 x 3 factorial arrangement. The trial involved 84
      crossbred pigs (26 kg initial BW) allotted to pens of two pigs each (one gilt,
      one barrow). Serum was obtained from all pigs on d 0, 3, 7, 21, 35, 63, and 77 of
      the 83- or 90-d feeding period. Tissue samples (liver, leg, and neck muscle,
      backfat, and leaf fat) were collected from one pig (barrow) in each pen at the
      end of the feeding period. Average daily gain and gain:feed were .93 kg and .30,
      respectively, without treatment differences (P > .10). Serum alpha-tocopherol
      increased linearly (P < .01) by d 3 with increasing level of dietary vitamin E
      supplementation. High dietary vitamin A resulted in a small decrease (P < .01) in
      serum alpha-tocopherol on d 3, but serum alpha-tocopherol concentration was not
      affected (P > .10) on other days. Tissue alpha-tocopherol increased linearly (P <
      .001) as dietary vitamin E increased in all tissues examined. No consistent
      evidence was found to indicate that a high level of dietary vitamin A interfered
      with performance or with blood serum or tissue alpha-tocopherol concentrations in
      growing-finishing swine.

PMID- 7628954
TI  - Dietary fiber for dogs: IV. In vitro fermentation of selected fiber sources by
      dog fecal inoculum and in vivo digestion and metabolism of fiber-supplemented
      diets.
AB  - Two experiments were conducted to evaluate single sources and blends of dietary
      fiber in dog food. In Exp. 1, 14 fibrous substrates were fermented in vitro using
      dog feces as the source of inoculum. Organic matter disappearance was lowest (P <
      .05; < 10%) for Solka Floc and oat fiber and greatest (P < .05; > 80%) for
      fructooligosaccharides (FOS) and lactulose. Solka Floc, oat fiber, gum karaya,
      and xanthan gum produced the least (P < .05; < 1 mmol/g of substrate OM) total
      short-chain fatty acids (SCFA). Lactulose, citrus pectin, and guar gum produced
      the greatest (P < .05; > 6.8 mmol/g of substrate OM) total SCFA. In Exp. 2, six
      diets were formulated based on results obtained in Exp. 1. Treatments included 1)
      beet pulp (BP), 2) Solka Floc (SF), 3) citrus pulp (CP), 4) stool blend (SB), 5)
      SCFA blend (SC), and 6) combination blend (CB). Digestibility of DM and total
      dietary fiber (TDF) was greatest (P < .05; 87.3 and 60.8%, respectively) for dogs
      consuming the SC diet. Feces from dogs fed SC were scored as more unformed and
      liquid in consistency than feces from dogs fed the other diets. Dogs consuming
      the SF and SB diets had the lowest (P < .05; 11.0 and 4.1%, respectively) TDF
      digestibilities. Organic matter disappearance values derived from substrates
      fermented in vitro reasonably predicted the fiber digestibility of diets fed to
      dogs. Moderately fermentable dietary fiber sources, such as BP, promote excellent
      stool characteristics without compromising nutrient digestibility, and may
      promote gastrointestinal tract health by optimizing SCFA production.

PMID- 7628955
TI  - In vitro fermentation of selected fibrous substrates by dog and cat fecal
      inoculum: influence of diet composition on substrate organic matter disappearance
      and short-chain fatty acid production.
AB  - Two in vitro fermentation experiments were conducted to evaluate the influence of
      source of dietary fiber fed to dogs and cats on fermentative activity of their
      fecal microflora. In Exp. 1, six English Pointer dogs were fed a diet containing
      either a non-fermentable fiber (Solka Floc) or a fermentable fiber (citrus pulp).
      A fecal sample from each dog was used as the inoculum source to determine in
      vitro OM disappearance (OMD) and short-chain fatty acid (SCFA) production from
      selected fibrous substrates. When data were pooled across substrates and
      fermentation times, a lower (P = .02) OMD (24.8 vs 29.4%) and a higher (P = .01;
      3.8 vs 2.2) acetate to propionate ratio (A:P) occurred for the Solka Floc than
      for the citrus pulp diet. In Exp. 2, six short-hair cats were fed a diet
      containing no supplemental fiber (NF) or a diet containing beet pulp (BP). When
      data were pooled across substrates and fermentation times, NF resulted in a
      greater (P < .01) A:P than the BP diet (3.4 vs 1.5). The BP treatment resulted in
      a slightly higher (P = .07) OMD (42.0 vs 39.3%) and a higher (P = .07) propionate
      production (.74 vs .47 mmol/g of OM) than the NF diet. In summary, in vitro
      substrate OMD increased and A:P decreased when fecal inoculum from dogs and cats
      fed diets containing a supplemental source of fermentable fiber was used. In
      vitro fermentation of fibrous substrates by fecal microflora from dogs and cats
      increased with inclusion of fermentable fiber in the diet.

PMID- 7628956
TI  - Effect of chromium tripicolinate on growth, glucose tolerance, insulin
      sensitivity, plasma metabolites, and growth hormone in pigs.
AB  - Two experiments were conducted to evaluate the effect of Cr as Cr tripicolinate
      (CrPic) on growth, glucose tolerance, insulin sensitivity, plasma metabolites,
      and growth hormone (GH) in pigs. Pigs were fed a control diet or a diet
      supplemented with 200 micrograms of Cr/kg of diet as CrPic. Thirty (15 per diet,
      initial BW was 21.3 kg) and 24 (12 per diet, initial BW was 24.9 kg) crossbred
      barrows were used in Exp. 1 and 2, respectively. The diets were formulated to
      provide 120% of the lysine requirement for 20- to 50-kg pigs. A glucose tolerance
      test (IVGTT; 500 mg of glucose/kg BW) and an insulin challenge test (IVICT; .1 IU
      of porcine insulin/kg BW) were conducted. In addition, during Exp. 1, a GH
      releasing hormone (GHRH) challenge was conducted. All data were pooled across
      experiments, except where noted. Average daily gain, ADFI, gain/feed, and fasting
      (15 to 18 h) plasma glucose and total protein concentrations were not affected (P
      > .10) by dietary treatment. Fasting plasma cholesterol (P < .05) was increased
      and NEFA (Exp. 2 only, P < .02), urea N (P < .07), and insulin (P < .10)
      concentrations were decreased in pigs fed CrPic. During the IVGTT and IVICT,
      glucose disappearance rate (k, percentage/minute) was increased (P < .04) and
      glucose half-life (t1/2, minutes) was decreased (P < .04) in pigs fed CrPic;
      however, insulin kinetics were not altered (P > .10). During the GHRH challenge,
      pigs fed CrPic had decreased (P < .09) area under the response curve for
      GH.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7628957
TI  - Effect of substitution of starch for fiber and fat in isoenergetic diets on
      nutrient digestibility and reproductive performance of rabbits.
AB  - The optimal level of starch in diets for rabbit does was investigated. Five
      isoenergetic and isoproteic diets containing 26.6, 24.6, 19.0, 16.8, or 13.0%
      starch and 31.2, 33.4, 36.0, or 41.2% NDF, respectively (DM basis), were made by
      substitution of starch for NDF and fat. The effect of diet on nutrient
      digestibility was determined in fattening and nonlactating and lactating adult
      does using a total of 105 rabbits. Increasing dietary starch content linearly
      increased (P < .001) DM, GE, CP (P = .07), and starch digestibilities but
      decreased (P < .001) NDF digestibility. Nutrient digestibility was higher (P <
      .05), except for CP, in adult does than in fattening rabbits. Dry matter and GE
      digestibilities were higher (P = .08) for nonlactating than for lactating does. A
      lactation trial using 440 rabbit does was conducted over a 6-mo experimental
      period. Milk production and milk composition were measured in 70 lactations. A
      decrease in dietary starch content did not improve pup mortality before weaning
      but impaired (linear, P < .001) dry feed intake and pup growth from 21 d until
      weaning. Diet did not influence does' feed intake, milk DM, ether extract, and CP
      contents or prolificacy. However, diet had quadratic effects on milk production
      (P = .15), milk lactose content (P = .07), parturition interval (P = .02), and
      feed conversion efficiency (P = .02), expressed both per weight or number of pups
      weaned. Optimal values were reached for dietary starch and NDF contents at
      approximately 20 and 35.5% (DM basis), respectively.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7628958
TI  - Free and total ion concentrations in pig digesta.
AB  - Mineral bioavailability is related to the activity of the free ion or small
      ligand metal ion complexes present in gastrointestinal (GI) tract digesta.
      Therefore, it is necessary to distinguish between total ion and free-ion/small
      ligand complexes (referred to simply as "free") concentrations. Free and total
      cation concentration in pig digesta from various GI locations were determined.
      Free ions were operationally defined as those that passed through a 1,000
      molecular weight cutoff filter. To test the effect of dietary supplementation on
      free ion concentrations, pigs were fed either basal diets of corn bran, corn
      grits, and soybean meal (10, 67, and 20 weight percent, respectively) or basal
      diets containing added Ca, Zn, Fe, and Cu. In addition, the Ca and K content of
      corn bran fragments retrieved from digesta was determined by energy dispersive x
      ray analysis to examine whether this dietary fiber preferentially absorbed
      minerals, thus reducing mineral bioavailability. Free cation concentrations,
      expressed as a percentage of the total, averaged over all locations for both
      diets were: Na, 86%; K, 96%; Ca, 11%; Mg, 40%; Zn, 5%; Fe, 4%; and Cu, 11%. For
      Ca, Mg, Zn, and Cu, the free:total cation concentration ratios differed (P < .05)
      between upper and lower GI tract. Mineral supplementation did not alter
      free:total ratios of any ion in the GI tract. For supplemented diets, mineral
      concentrations generally were higher throughout the GI tract, as were
      concentrations of free Ca. Free concentrations of Zn and Cu in the jejunum and
      ileum were higher (P < .01) with supplemented diets.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7628960
TI  - Technical note: subjective enumeration of episodic events (spikes) in animal
      physiology experiments.
AB  - Blood samples of nine sheep were taken over time and analyzed for estrone,
      estradiol, and progesterone. Results were plotted for each sheep, and graphs were
      evaluated by 26 evaluators with various previous experience. Sheep were sampled
      for different time periods. Repeatabilities for the number of spikes of estrone,
      estradiol, and progesterone recorded for sheep were variable, ranging from .019
      to .547. Repeatabilities for evaluators ranged from .033 to .427, but these
      values decreased to < .001 to .030 when adjusted by covariance for the number of
      spikes possible. Results indicated that either an objective procedure for
      counting spikes should be used in comparable research or that evaluators should
      be trained in visual counting procedures to improve their repeatability.

PMID- 7628959
TI  - Biogenic amines in the hypothalamus of rats after diethyldithiocarbamate or AIMAX
      treatment, an alternative for norepinephrine depletion.
AB  - The objective of this study was to determine whether AIMAX (a
      dithiocarbamoylhydrazine derivative) is suitable for determining the effects of
      norepinephrine (NE) depletion on reproduction in domestic animals. Therefore, the
      effect of AIMAX (n = 6) on concentrations of biogenic amines in the medial basal
      hypothalamus (MBH) and anterior hypothalamic area (AHA) of ovariectomized (OVX)
      rats primed with ovarian steroids was compared to that of diethyldithiocarbamate
      (DDC; n = 5), a potent dopamine-beta-hydroxylase (DBH) inhibitor, which is
      chemically similar to AIMAX. Rats that received only ovarian steroids and saline
      injections served as controls (n = 6). Treatment with DDC resulted in sedation
      and reduced body temperature. In contrast, rats behaved normally after AIMAX
      treatment. AI-MAX reduced (P < .05) NE but increased (P < .05) dopamine (DA)
      concentrations in MBH and AHA compared with controls. Similar changes in NE and
      DA concentrations were observed in DDC-treated rats. However, elevated
      epinephrine (EPI) levels were measured in MBH and AHA of only DDC-treated rats.
      Serum LH concentrations were suppressed (P < .005) in both AIMAX- and DDC-treated
      rats compared with control animals. Because AIMAX, like DDC, suppressed
      hypothalamic NE content and LH secretion, AIMAX should be useful in studying
      effects of NE depletion on gonadotropin secretion in domestic animals.

PMID- 7628961
TI  - Influence of maternal and service-sire breed on serum progesterone and estrogen
      before calving and plasma 13,14-dihydro-15-keto-prostaglandin F2 alpha after
      calving.
AB  - Effects of breed of service sire and cow on birth weight and prepartum and
      postpartum endocrine function were studied in multiparous Brahman (n = 20) and
      Angus (n = 20) cows bred to Brahman or Angus bulls. Before calving, blood samples
      were collected on d 34 to 28, 27 to 21, 20 to 14, and 13 to 7, and after calving,
      samples were collected from d 0 to 7. Progesterone (P4), estrogen (E2), and 13,14
      dihydro-15-keto-prostaglandin F2 alpha (PGFM) were quantified with RIA. Calves
      born to Brahman were smaller (P < .05) than calves born to Angus cows. Prepartum
      concentrations of P4 were greater in Angus cows and decreased more rapidly near
      parturition than in Brahman cows (breed of dam x period; P < .03). Cows bearing
      bull calves had greater concentrations of P4 on d 20 to 14 before calving than
      cows bearing heifer calves (sex of calf x period; P < .04). Prepartum E2 was
      influenced (P < .05) by the breed of dam x breed of sire x period interaction.
      The ratio of P4:E2 tended to decrease more in Angus than in Brahman cows near
      parturition (breed of dam x period; P < .09). Postpartum PGFM tended to be
      influenced (P < .08) by breed of dam x breed of sire; from d 3 to 5, Brahman cows
      bred to Angus bulls tended (P < .08) to have greater PGFM than Brahman cows bred
      to Brahman bulls or than Angus cows bred to Brahman or Angus bulls.2+ f1p4

PMID- 7628962
TI  - Diet quality and ruminal digestion in beef cattle grazing midgrass prairie
      rangeland or plains bluestem pasture throughout the summer.
AB  - Beef cattle fitted with esophageal (four steers/pasture) or ruminal and duodenal
      (six calves/pasture; beginning BW +/- SE = 267 +/- 6 kg) cannulas grazed midgrass
      prairie rangeland (excellent range condition; MIDGRASS) or plains bluestem
      (Bothriochloa ischaemum var. Plains) pasture (BLUESTEM) in mid-May, late-June,
      mid-August, and mid-October of 1990 and 1991. Nitrogen in masticate samples
      collected from MIDGRASS was lowest (P < .05) in June and August across both
      years. The N in BLUESTEM masticate peaked (P < .05) in August 1990, but N was
      lowest (P < .05) in August 1991. The detergent fiber content of masticate from
      both forages increased (P < .05) as the grazing season advanced from May through
      August; fall regrowth in October occasionally resulted in a small decrease (P <
      .05) in fiber content. In vitro OM disappearance (IVOMD) followed a pattern
      similar to N content. The IVOMD of BLUESTEM masticate was greater (P < .05) than
      that of MIDGRASS masticate. The ruminal ammonia N concentration
      (milligrams/deciliter) in cattle grazing BLUESTEM (4.5) usually was greater (P <
      .05) than in cattle grazing MIDGRASS (3.3). In situ OM and N disappearance was
      greater (P < .05) from BLUESTEM masticate than from MIDGRASS masticate in May,
      June, and August. The ruminally degraded N:ruminally degraded OM ratio
      (grams/kilograms) estimated from in situ digestion suggested that cattle grazing
      MIDGRASS during the mid-summer of both years and BLUESTEM in August 1991 may have
      been marginally deficient in ruminally degraded N. Plains bluestem pasture would
      complement MIDGRASS by providing better quality grazing during the mid-summer.

PMID- 7628963
TI  - Influence of processing supplemental alfalfa on intake and digestion of dormant
      bluestem-range forage by steers.
AB  - Four ruminally and duodenally fistulated, 2-yr-old Angus x Hereford steers
      (average initial BW = 370 kg) were used to evaluate the effect of method of
      processing supplemental alfalfa on intake and digestion of dormant bluestem-range
      forage (2.8% CP, 78% NDF). Treatments (4 x 4 Latin square) were 1) control, no
      supplement; 2) ground and pelleted alfalfa hay (PELLET; 21% CP, 37% NDF); 3)
      ground and pelleted dehydrated alfalfa (DEHY; 21% CP, 44% NDF); and 4) longstem
      alfalfa hay (HAY; 20% CP, 37% NDF). All supplements were from a single cutting of
      alfalfa and fed at .5% BW (as-fed basis). Supplementing steers with alfalfa
      increased (P < or = .07) bluestem forage OM intake (FOMI); total OM intake
      (TOMI); true ruminal OM digestibility; total tract OM digestibility (TTOMD);
      total N, microbial N, and nonammonia-nonmicrobial N (NANM) flows to the duodenum;
      ruminal OM and fluid fill; fluid dilution rates; dietary DE concentration; and
      ruminal total VFA and NH3 N concentrations. Because of the enhanced FOMI and TOMI
      associated with alfalfa supplementation and the concomitant improvement in TTOMD,
      digestible OM intake (DOMI) also increased (P < .01) when supplemental alfalfa
      was fed. Method of processing alfalfa had little impact on forage utilization,
      except FOMI (P = .11), TOMI (P = .10), and ruminal OM fill (P = .09) tended to be
      greater when supplemental alfalfa pellets were dehydrated. Similarly, processing
      method tended to alter the molar proportions of some minor VFA. In conclusion,
      alfalfa supplementation exerted a dramatic impact on utilization of low-quality
      forage.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7628964
TI  - Effect of supplemental fish meal protein on site and extent of digestion in beef
      steers.
AB  - The effects of supplemental fish meal on site and extent of digestion were
      determined using four steers equipped with ruminal, duodenal, and ileal cannulas.
      Fish meal was included in diets to supply 0 (0FM), 25 (25FM), 50 (50FM), or 75
      (75FM) g of N daily above the CP requirement of a 400-kg steer gaining 1.2 kg/d.
      Total tract starch digestibility tended to be greatest for 25FM (95%), lowest for
      0FM (90%), and intermediate for 50FM (94%) and 75FM (92%). Total tract N
      digestibility was greatest for 25FM, lowest for 0FM, and intermediate for 50FM
      and 75FM (cubic, P < .05). Total tract starch digestibility increased .46
      percentage units for each unit increase in N digestibility (n = 16, P = .03).
      Ruminal starch digestibility was greatest for 25FM, intermediate for 50FM and
      75FM, and lowest for 0FM (quadratic; P < .10). Starch flow to the duodenum was
      decreased for 25FM and 50FM vs 0FM and 75FM (quadratic, P < .10) and N flow to
      the duodenum was increased (linear, P < .01) by fish meal. Fish meal
      supplementation increased N digestibility (quadratic, P < .05) but had no effect
      (P > .10) on starch digestibility in the small intestine. Starch digestibility in
      the small intestine was not related to N flow to the duodenum; however, starch
      digestibility increased .9 percentage units for each percentage unit increase in
      N digestibility (n = 16, P = .02). Fish meal supplementation tended to increase
      total tract starch digestibility by increasing ruminal, but not small intestinal,
      digestibility.

PMID- 7628965
TI  - Relative bioavailability of two organic and two inorganic zinc sources fed to
      sheep.
AB  - A study was conducted to compare supplemental Zn lysine (ZnLys), Zn methionine
      (ZnMet), ZnSO4, and ZnO on Zn, Cu, and metallothionein (MT) concentrations in
      various fluids and tissues of 40 wether lambs. Supplemental Zn (360 mg/kg) was
      fed for 3 wk, withdrawn for 4 wk, and then resumed for another week. Mineral (Zn
      and Cu) concentrations were determined in serum, liver, pancreas, kidney, bone,
      bone marrow, hoof, and leg muscle, and only Zn was determined in skin and cornea.
      Metallothionein concentration was determined in liver, pancreas, and kidney. By d
      49 serum Zn had increased less (P < .05) for controls than for all lambs except
      those fed ZnMet, and on d 55 it had increased more (P < .05) for ZnLys than for
      all but ZnSO4. There were no treatment effects in serum Cu concentration, but
      overall Cu concentration fell slightly for all treatments from d 0. The ZnLys
      treated lambs had the highest (P < .05) Zn accumulation (581, 389, and 340 mg/kg)
      in kidney, liver, and pancreas, respectively. Both ZnSO4- and ZnMet-treated lambs
      had higher (P < .05) liver Zn concentrations (195 and 198 mg/kg, respectively)
      than the control lambs (127 mg/kg). Mean Zn concentration of bone, bone marrow,
      cornea, skin, hoof, and muscle was not different (P > .05) for lambs among
      treatments. The ZnLys-treated lambs had the highest (P < .05) MT concentrations
      (79, 167, and 68 micrograms MT/g for liver, kidney, and pancreas, respectively).
      Mean muscle Cu concentration was highest (P < .05) for controls (10
      mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7628966
TI  - Technical note: assessing the consistency of measurement procedures in animal
      energetics and nutrition.
AB  - Our objective was to assess the consistency of representative digestion and
      energetics determinations used in animal nutrition. We used distribution theory
      of quadratic forms that allow for the attainment of width of confidence intervals
      (WI) for intraclass correlations. Three models commonly used in animal nutrition
      were analyzed, and their respective programs were coded to obtain the required
      confidence limits. Data sets were obtained from previous research published by
      our laboratory. Urinary, CH4, and ME were analyzed assuming a two-factor nested
      balanced variance component model. Rate of ruminal NDF disappearance (kd) and DM
      digestibility by an 8-d conventional collection trial were fitted to a two-factor
      crossed variance component model without interaction with a single observation
      per cell. Empty BW (EBW), carcass energy, and EBW energy were fitted to a two
      factor crossed variance component model with interaction. Widths of confidence
      intervals varied with the example data set and variable tested. The narrowest WI
      was that of DM digestibility, less than .07 at a 95% confidence level for all the
      intraclass correlations, which shows the high consistency of the DM digestibility
      measurement in the specific study. Medium to large WI were found for kd and EBW;
      WI estimates were less than .70 at a 95% confidence level. Large WI, from .8 to
      1.0 at a 95% confidence level, were found for the remaining variables, indicating
      the greater variability of these measurements. This methodology allows the
      assessment of the consistency of a measurement process and provides a method to
      monitor it each time a determination is made.

PMID- 7628967
TI  - Rapid communication: variable number of tandem repeat marker, RVF9401, in rainbow
      trout.

PMID- 7628968
TI  - Rapid communication: variable number of tandem repeat marker, RVF9303, in rainbow
      trout.

PMID- 7628969
TI  - Characteristics and efficiency of fast-growing feedlot steers fed different
      dietary energy concentrations.
AB  - Most prediction equations of feedlot performance cover average daily gains (ADG)
      below 1.5 kg/d. The question is whether these equations would be accurate for
      higher ADG. Medium-to-large-framed weanling and yearling steer calves were fed
      individually using a transponder-electronic gate system in three feedlot trials
      and fed in groups in two trials. Average daily gain ranged from .9 to 2.1 kg.
      Steers were implanted, fed to the same degree of finish, and slaughtered to
      obtain dressing percentage and cold carcass weight. Initial carcass weights were
      estimated from initial slaughter groups. Dietary ME concentration (i.e., 10.5,
      11.5, 12.0, and 12.5 MJ ME/kg of DM, where 1 Mcal = 4.184 MJ), initial weight,
      dry matter intake (DMI), and days fed could explain 57% of the variation in ADG.
      The partial contribution of DMI to the total variation was only 5.2%, confirming
      the low correlation between DMI and ADG in feedlot trials. The correlation
      between metabolizable energy intake (MEI) and MEI/ADG also was low, but 80% of
      the variation in MEI/ADG was accounted for by the variation in ADG. Intake
      patterns, regardless of dietary energy concentration, indicate that ADG increased
      with DMI only when ADG was below 1.5 kg/d. Therefore, current prediction
      equations apparently overpredict ME requirements for fast-growing feedlot steers.
      Optimal performance occurred at a ME concentration of 12.0 MJ/kg of DM rather
      than 12.5 MJ/kg of DM. Dressing percentage and carcass gain increased as dietary
      energy concentration and ADG increased, and current prediction equations should
      predict that of fast-growing feedlot steers equally well.

PMID- 7628970
TI  - Increased postweaning gain of beef heifers enhances fertility and milk
      production.
AB  - Four hundred fifty-two (452) weanling heifer calves (192 +/- 23 kg) were used to
      determine the effect of postweaning weight gain on subsequent reproductive
      performance and lactation. Heifers grazed stockpiled tall fescue pastures and
      were fed a high (H) or low (L) amount of ground corn supplement (3.68 and 2.99
      kg/[animal.d], respectively) during a postweaning treatment period of 136 d.
      Postweaning gain of heifers receiving L and H was .43 and .62 kg/d, respectively.
      These treatments resulted in a range of postweaning gain from .07 to 1.17 kg/d.
      Heifers receiving H were 26 kg heavier (P < .01), had .15 cm more fat thickness
      (P < .01), 5% greater pelvic area (P < .01), and tended (P = .08) to have greater
      hip height than heifers receiving L at yearling. More heifers in the H group were
      pubertal before the start of the breeding season (70.9 vs 61.3%) (P < .05). No
      significant differences were found in pregnancy rate or first-service calving
      rate between treatment groups. Mean milk production was 10% greater for H- than
      for L-fed heifers (P < .01) and resulted in heavier calves at 54, 104, and 153 d
      of age (P < .05). Regression analysis revealed that as weaning weight and
      postweaning gain increased, so did the probability for reaching puberty before
      the breeding season. Increasing weaning weight also increased the probability of
      calving to the first AI service. As heifer weaning weight and postweaning gain
      increased, subsequent milk production also increased. Increasing postweaning
      weight gain of lightweight heifers from .07 to 1.17 kg/d increased both
      reproductive and lactation performance.

PMID- 7628971
TI  - Effect of ruminally undegradable protein from fish meal on growth and
      reproduction of peripuberal Brahman bulls.
AB  - Thirty-nine Brahman bulls (301.7 +/- 4.1 d; 202.7 +/- 4.7 kg) were allotted to
      one of two treatments and fed soybean meal (SBM)- or fish meal (FIS)-based
      supplements and hay to examine the effects of source of protein on growth and
      reproductive development. The fish meal supplement had 72% ruminally undegradable
      protein (RUP) and the soybean meal supplement had 47% RUP. Bulls assigned to the
      FIS treatment had higher (P < .01) total weight gain (81.2 +/- 1.4 vs 71.2 +/-
      2.2 kg), higher (P < .01) ADG (.97 +/- .02 vs .85 +/- .03 kg), and better (P <
      .05) feed:gain ratio (7.6 +/- .1 vs 8.6 +/- .1 feed/BW gain for FIS vs SBM,
      respectively). Age at first motile spermatozoa was not affected (P > .05) by
      source of protein (429.9 +/- 9.6 vs 427.2 +/- 9.5 d, for bulls receiving FIS or
      SBM supplements, respectively). Likewise, age at puberty (473.3 +/- 21.7 d vs
      465.9 +/- 12.9 d for bulls receiving FIS and SBM supplements, respectively) was
      similar for both treatment groups. There were no differences between treatments
      in scrotal circumference at those stages. At puberty semen quality was similar
      for bulls receiving FIS or SBM treatments, and no differences existed in LH and
      testosterone concentrations between treatments. We conclude that fish meal
      supplement increased growth but did not alter reproductive parameters in Brahman
      bulls.

PMID- 7628972
TI  - Improved synchrony, conception rate, and fecundity in postpartum suckled beef
      cows fed melengestrol acetate prior to prostaglandin F2 alpha.
AB  - Occurrence of estrus, conception rate, and fecundity were compared between
      postpartum suckled beef cows fed or not fed melengestrol acetate (MGA) before
      synchronizing estrus with prostaglandin F2 alpha (PG). One hundred thirty-three
      purebred Angus cows were stratified by age and days postpartum to one of two
      treatments. All cows received an injection containing 25 mg of PG; however, one
      group (MGA+PG) was fed .5 mg of MGA.cow-1.d-1 for 14 d then received PG 17 d
      after the last feeding of MGA. The other group (PG) received only PG. Cows in
      both treatments that failed to exhibit estrus within 6 d after PG received a
      second injection of PG 11 d after the first injection was administered. Cows were
      checked for estrus from the first PG injection until 6 d after the second PG
      injection. Cows were inseminated with semen from a 3/4 Brahman bull 12 h after
      observed estrus. Cows were exposed to Angus bulls after the AI period. Conception
      date was determined by palpation per rectum and verified by calving date and calf
      phenotype. Differences in response variables were analyzed by chi-square. A
      greater proportion of cows (P < .04) that were pretreated with MGA exhibited
      estrus after the first injection of PG (76%) than of cows that received only PG
      (60%). Total response did not differ between treatments after both injections of
      PG. Conception rate among cows that received a first service was higher (P <
      .007) for the MGA+PG (88%) group than for the PG (67%) group, although the total
      number of cows that received a first service was not different between
      groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7628973
TI  - Detection of fetal twins in sheep using a radioimmunoassay for pregnancy-specific
      protein B.
AB  - Ovine pregnancy-specific protein B (oPSPB) was isolated from sheep placentas.
      Antiserum to oPSPB was developed in rabbits. A quantitative RIA was developed and
      used to assay the serum concentrations of oPSPB during and after pregnancy in
      ewes bearing single or twin fetuses. Suffolk and Panama ewes, kept with rams
      equipped with a marking harness, were checked daily for breeding marks as an
      indication of estrus and bled daily between 10 and 30 d after marking. Ovine PSPB
      became detectable at 19.7 +/- .14 (mean +/- SE) d after breeding and increased
      steadily to d 30. Panama oPSPB concentration increased at a greater rate than
      that of Suffolks (breed x day interaction, P < .01). Ten ewes were bled twice
      weekly 3 wk before their expected date of lambing and weekly for 7 wk postpartum.
      Serum concentrations differed considerably between prepartum ewes, but
      concentrations remained stable within the period of 20 d prepartum. Following
      parturition, oPSPB concentrations dropped rapidly. In nine ewes, oPSPB was last
      detectable at 12.78 +/- 2.26 (mean +/- SE) d postpartum. In the 10th ewe, oPSPB
      was .65 ng/mL at the last sample on d 46 postpartum. To determine the effect of
      fetal number on oPSPB concentrations, ewes in which estrus was synchronized were
      bled at d 18, 25, 38, 60, 90, and 120 after breeding. Ewes were killed at d 60,
      90, 120, and 148 and fetal number determined. There was a significant (P < .01)
      difference in the log of oPSPB concentrations according to number of fetuses, day
      postbreeding, and the day x fetal number interaction.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7628974
TI  - Transvaginal aspiration of oocytes from hormone-treated pregnant beef cattle for
      in vitro fertilization.
AB  - The ability to produce oocytes from genetically valuable, pregnant donors in a
      safe, repeatable manner would broaden the application of in vitro fertilization
      (IVF) procedures for beef and dairy cattle. The objectives of this study were to
      evaluate two gonadotropin treatment schedules for follicle stimulation of
      pregnant donor cattle and to determine the efficacy and safety of the repeated
      oocyte aspiration procedure from pregnant cattle. In Exp. 1, pregnant donors at
      60 to 90 d of gestation were randomly allotted to three treatment groups. Cows in
      Treatment A received a total dose of 40 mg of FSH. Cows in Treatment B were
      administered a total of 20 mg of FSH, and females in Treatment C served as
      pregnant vehicle-treated controls. A group of luteal phase cows received a total
      of 40 mg of FSH and served as nonpregnant controls (Treatment D). Ultrasound
      guided transvaginal oocyte aspiration was performed 12 h following the last FSH
      or saline injection. Following follicle aspiration, oocytes were matured for 24 h
      and then entered a standard bovine IVF procedure. Experiment 2 was conducted to
      determine the repeatability of this procedure on first trimester cows. Cows in
      Exp. 2 were selected (after a 20-d recovery period) from each of the three
      pregnant treatment groups in Exp. 1 and each given 40 mg of FSH before a second
      oocyte aspiration procedure. The number of follicles aspirated per cow in
      treatment groups receiving the high FSH dose treatment (40 mg of FSH total dose)
      was not different (Treatment A, Treatment D, and cows in Exp. 2).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7628975
TI  - Plasma cortisol and white blood cell responses in different breeds of bulls: a
      comparison of two methods of castration.
AB  - To determine plasma cortisol and white blood cell response to castration, Angus
      (n = 12, 21.4 mo of age), Hereford (n = 6, 21.2 mo of age), and Brahman (n = 24,
      20.3 mo of age) bulls nearing maturity were either left intact as uncastrated
      controls (CON), surgically castrated (SUR) after lidocaine, or castrated by latex
      rubber banding (BAN). Before and through 35 d after castration (castration = d
      0), animals were weighed and blood samples were collected for analysis of
      cortisol and total white blood cell (WBC) count at 2-, 3-, or 7-d intervals.
      There was a treatment x breed interaction for ADG from d 0 to 7 (P < .05). From d
      0 to 14, 0 to 21, 0 to 28, and 0 to 35, ADG tended to be lower for SUR and BAN
      animals than for CON animals (castrated vs CON, P < or = .13). No significant
      differences in ADG were observed between SUR and BAN animals during these times.
      On d 0, from just before treatment to just after treatment, plasma cortisol
      concentration increased 3.2 ng/mL for SUR and .1 ng/mL for BAN (SEM = +/- .5
      ng/mL; SUR vs BAN, P < .03). From d 0 pretreatment to d 2 after treatment, plasma
      cortisol concentration increased 1.5 ng/mL for castrated (SUR = 2.0 and BAN = 1.1
      ng/mL) and decreased 1.6 ng/mL for CON (SEM = +/- .7 ng/mL; P < .04). Plasma
      cortisol concentration was negatively correlated (P < .001) with BW (r = -.17)
      and BW change (r = -.19).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7628976
TI  - Dust suppression in swine feed using soybean oil.
AB  - Dust generation from swine feed (corn-soybean meal diet) treated with soybean oil
      was investigated using a cement mixer in a plywood box. Airborne total dust
      concentrations in the box were measured gravimetrically using a vacuum pump and
      filters while 12-kg feed samples were constantly mixed. The treatment factors
      were soybean oil concentration (0, 1, and 3%), corn bulk density (normal, 730
      kg/m3 and low, 600 kg/m3), time of oil addition (before vs after grinding the
      corn), and storage time (0, 7, and 14 d). The feed was a mixture of soybean meal,
      base mix, and adjusted amounts of ground corn and soybean oil. Adding soybean oil
      after grinding at 1 and 3% levels to feed made with normal-bulk density corn
      suppressed total dust generation (3.39 and .99 mg/m3, respectively) (P < .001)
      compared with the no oil treatment (29.1 mg/m3). The 3% soybean oil treatment
      suppressed dust generation (.99 mg/m3) more than the 1% soybean oil treatment
      (3.39 mg/m3) (P < .001). Adding soybean oil after grinding the corn suppressed
      dust generation more than adding the oil to the corn before grinding for every
      oil level (P < .001). More dust was generated by feed made from low-bulk density
      corn than by feed made with normal-bulk density corn at every oil level (P <
      .001). There was no evidence of any storage time or treatment x storage time
      interactions.

PMID- 7628977
TI  - Effect of prenatal androgenization on performance, lactation, carcass, and
      sensory traits of heifers in a single-calf heifer system.
AB  - Twenty-four prenatally androgenized (PA) heifers, born to testosterone propionate
      implanted cows, and 27 control (C) heifers, born to nonimplanted cows, were bred,
      calved, and placed in drylot pens, with calf at side, to assess the effects of PA
      on feedlot growth and lactational performance of heifers used in a single-calf
      heifer (SCH) system. Lactating heifers were fed an 85% concentrate diet, calves
      weaned at 117 d postpartum, and heifers slaughtered at a constant compositional
      end point of 1.1 cm of s.c. fat. Preweaning, PA heifers gained 22.5% faster (P <
      .01) and were 17.3% more efficient (P < .01) than controls. Prenatal
      androgenization of the heifer, however, did not affect calf growth performance.
      All calves gained more than 1.4 kg/d and had an average weaning weight of 159 kg
      at 117 d of age. Combining heifer-calf weights, PA and C pairs gained 2.88 and
      2.53 kg/d, respectively. Correcting for DMI of calves, PA improved (P < .01)
      efficiency of beef production 10.8%. Four percent fat-corrected milk yield of PA
      and C heifers averaged 7.96 and 7.60 kg/d, respectively, and the percentage of
      milk protein and fat did not differ. Accounting for average BW, milk production,
      and DMI, PA and C lactating heifers should have gained 1.27 kg/d; however, gains
      were 137 and 127% of those predicted, respectively. Overall, pre- and
      postweaning, PA heifers required 10 fewer (P < .04) days on feed, gained 23%
      faster (P < .01), and were 16% more efficient (P < .02) than C heifers. At
      slaughter, PA and C heifers averaged 853 and 865 d of age, respectively.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7628978
TI  - Within-herd genetic analyses of stayability of beef females.
AB  - Nonlinear mixed-model procedures for analysis of binary data were used to
      estimate heritability (h2), predict individual genetic merit, and determine
      genetic and environmental trends for four measures of stayability of beef
      females. Traits considered were probabilities of a female having 2 [S(2/1)], 5
      [S(5/1)], 8 [S(8/1)] and 11 [S(11/1)] calves, given that she calved once.
      Colorado State University Beef Improvement Center (BIC) and Beckton Stock Farm
      (BSF) provided data for the analyses. Heritability was estimated using animal
      model marginal maximum likelihood (AM MML), sire model marginal maximum
      likelihood (SM MML), and animal model Method R (AM MR). Individual genetic merit
      was predicted using single-trait animal models with each h2 estimate. Birth year
      was treated as fixed in all analyses. Only AM MML yielded h2 estimates for all
      traits in both herds. The AM MML h2 estimates for S(2/1), S(5/1), S(8/1), and
      S(11/1) were .09, .11, .07, and .20, respectively, for BSF data and .02, .14,
      .09, and .07, respectively, for BIC data. Differing h2 estimates did not
      substantially influence rank of individual predictions. Genetic trends in
      stayability were positive in both herds, although birth year solutions indicated
      variable or negative environmental trends. Genetic improvement of stayability may
      be accelerated by incorporating predictions of genetic merit for stayability in
      selection criteria. S(5/1) may be the most useful trait for consideration in
      national cattle evaluations.

PMID- 7628979
TI  - Glycylcyclines: a new generation of tetracyclines.

PMID- 7628980
TI  - Aeromonas infections and their treatment.
AB  - With advances in the identification and molecular taxonomy of Aeromonas spp.,
      these organisms, which are widely distributed in the environment, are
      increasingly being recognised as human pathogens. Clinical infections include
      gastroenteritis, skin and soft tissue infections and bacteraemia. Antibiotic
      resistance poses a potential problem in the antimicrobial therapy of infections
      cased by Aeromonas spp. While most strains are susceptible to chloramphenicol,
      ciprofloxacin, co-trimoxazole and the aminoglycosides, the activity of
      amoxycillin/clavulanate and the acylureidopenicillins is inconsistent. Addition
      of a beta-lactamase inhibitor does not significantly enhance the activity of the
      acylureidopenicillins. Aztreonam and the carbapenems, imipenem and meropenem
      remain highly active. Although resistance to the first and second generation
      cephalosporins is variable, more than 90% of Aeromonas spp. are susceptible to
      the third generation agents. Of potential significance is the identification of
      chromosomally-encoded inducible beta-lactamases, associated with resistance to
      extended spectrum penicillins, cephalosporins, monobactams and carbapenems, in
      clinical isolates of Aeromonas spp. Two distinct enzymes are produced: the A1
      enzyme, a serine beta-lactamase behaving as a group 1 cephalosporinase, and the
      A2 enzyme, a metallo beta-lactamase which hydrolyses a wide range of beta-lactam
      agents including the carbapenems. The clinical relevance of these enzymes in
      Aeromonas spp. is unclear.

PMID- 7628981
TI  - The in-vitro activities of novel benzoxazinorifamycins against Mycobacterium
      leprae.
AB  - The activities of four newly synthesized benzoxazinorifamycin derivatives, either
      alone or in combination with ofloxacin, against strains of Mycobacterium leprae
      were determined by assessing their effects on two biochemical parameters of
      metabolic activity which served as surrogate markers for growth in vitro. KRM
      1648 and KRM-2312 were the most active agents tested against both a rifampicin
      susceptible isolate (MICs of 0.05 and 0.1 mg/L respectively) and a rifampicin
      resistant isolate (MICs of 0.2 and 0.3 mg/L respectively); both compounds were
      more active than either rifampicin or rifabutin. The activities of the two other
      derivatives, KRM-1657 and KRM-1668, against a rifampicin- susceptible strain
      (MICs of 0.3 mg/L) were similar to that of rifampicin, while the MIC of each of
      these agents for the rifampicin-resistant strain was 1.0mg/L. In common with
      rifabutin, both of the more active derivatives demonstrated synergy with
      ofloxacin against the rifampicin-susceptible isolates. The results of this study
      suggest that these compounds, in combination with ofloxacin as part of multidrug
      regimens, warrant further evaluation as treatment for patients with leprosy.

PMID- 7628982
TI  - Binding affinities of beta-lactam antibodies for penicillin-binding protein 2' in
      methicillin-resistant staphylococcus aureus.
AB  - We devised an accurate procedure with which to measure the affinities of beta
      lactam antibiotics for penicillin-binding protein (PBP) 2' in methicillin
      resistant Staphylococcus aureus (MRSA). In the present study, we used two
      isogenic strains of MRSA, on heterogeneous and the other homogeneous, derived
      from the methicillin-susceptible strain FDA209P, harbouring the mecA gene. In
      these MRSA strains, PBP2' was saturated by [14C]benzylpenicillin (PCG) at a
      concentration of 300 mg/L. In addition, the saturation of PBP2' by [14C]PCG
      required an incubation period of 30 min. According to these results, the precise
      affinities of beta-lactam antibiotics for PBP2' were determined by the 'accurate
      competition assay', using a high concentration of [14C]PCG and extending the
      reaction time. This procedure yielded lower IC50 values of beta-lactams than the
      'usual competition assay'. However, each beta-lactam had almost the same affinity
      for PBP2' in heterogeneous and homogeneous strains. These results suggest there
      is a factor(s) other than PBP2' responsible for controlling resistance levels and
      the heterogeneity or homogeneity of MRSA strains.

PMID- 7628983
TI  - Mode of action of metronidazole and a Bacteroides fragilis metA resistance gene
      in Escherichia coli.
AB  - The in-vivo mode of action of metronidazole and the MetA protein which confers
      resistance to metronidazole, was investigated in Escherichia coli wild type and
      DNA repair-deficient strains. All the E. coli strains were moderately susceptible
      to metronidazole under aerobic conditions but were more susceptible under
      anaerobic conditions, and the amount of DNA breakage was less under anaerobic
      than aerobic conditions. E. coli excision (uvr) and recombination (rec) mutants
      were more susceptible than DNA repair wild type strains. Metronidazole did not
      induce cell lysis in E. coli but caused single strand DNA breaks in wild type and
      repair-deficient E. coli strains. The MetA protein reduced DNA breakage caused by
      metronidazole in E. coli wild type and DNA repair-deficient strains grown under
      aerobic and anaerobic conditions, and inhibited the suppressor effect of the RecE
      protein in E. coli recBC strains. The MetA protein did not inactivate
      metronidazole.

PMID- 7628984
TI  - Prevalence of trimethoprim resistant dihydrofolate reductase genes identified
      with oligonucleotide probes in plasmids from isolates of commensal faecal flora.
AB  - In a recent survey of trimethoprim resistance, 357 Gram-negative aerobic
      organisms were isolated from healthy volunteers from rural and urban populations
      in South Africa. Trimethoprim resistance was transferable in 184 (52%) of the
      isolates. A further 12 (3%) transferred in the presence of an X+ actor. The
      transconjugants were probed with intragenic oligonucleotide probes for the type
      Ia, Ib, IIIa, VIII, V, VI, VII, IX, X and XII dihydrofolate reductase genes.
      Contrary to all previous data, the most prevalent dihydrofolate reductase gene
      was the type Ib (30%) followed by the type VIII (23%), V (13%), Ia (6%), VII
      (3%), and XII (0.5%). None of the strains hybridised to the type IIIa, XI, X and
      the VI dihydrofolate reductase probes. Plasmid restriction profiles revealed that
      the high prevalence of the type Ib and VIII dihydrofolate reductase genes
      resulted from the presence of ubiquitous plasmids. These results highlight the
      previous problems associated with the distinction of closely related
      dihydrofolate reductase genes.

PMID- 7628985
TI  - Biodistribution of liposomal amphotericin B (AmBisome) and amphotericin B
      desoxycholate (Fungizone) in uninfected immunocompetent mice and leucopenic mice
      infected with Candida albicans.
AB  - The biodistribution of liposomal amphotericin B (L-AmB; AmBisome) and
      amphotericin B-desoxycholate were compared after a single injection of drug in
      uninfected immunocompetent mice and in leucopenic mice 6 h after inoculation with
      Candida albicans. Amphotericin B-desoxycholate was administered at the maximum
      tolerated dose (MTD) of 0.3 mg/kg whereas L-AmB was given at either 0.3 mg/kg or
      the MTD of 7 mg/kg. Amphotericin B (AmB) concentrations in the blood, liver,
      spleen, lungs and kidneys were determined by HPLC analysis at various intervals
      during the 48 h after administration. The biodistribution of both preparations of
      AmB followed similar patterns in both uninfected immunocompetent mice as well as
      those that were leucopenic and infected with C. albicans. Administration of L-AmB
      resulted in increased concentrations of drug in the blood, liver, and spleen but
      decreased concentrations in the kidney and lung. Hepatosplenic uptake of L-AmB
      was highly dose dependent with 7 mg/kg resulting in a relatively prolonged blood
      circulation. Blood and tissues retained high AmB concentrations after
      administration of L-AmB at the MTD. By using radiolabelled L-AmB, it was found
      that the high AmB concentrations in blood represented liposome-associated AmB and
      that during circulation in blood slow release of AmB occurred.

PMID- 7628986
TI  - National survey of susceptibility to antimicrobials amongst clinical isolates of
      Pseudomonas aeruginosa.
AB  - Between September and December 1993, each of 24 hospitals in the UK collected up
      to 100 consecutive clinical isolates of Pseudomonas aeruginosa and sent these to
      the London Hospital Medical College (LHMC). Of 2184 cultures received, 1991
      contained viable P. aeruginosa. Minimum inhibitory concentrations (MICs) of
      antimicrobials were determined by agar dilution. The frequencies of resistance to
      low breakpoints were as follows: gentamicin, MIC > 2 mg/L, 11.7%; amikacin, MIC >
      4 mg/L, 10.5%, carbenicillin, MIC > 128 mg/L, 11.7%; azlocillin, MIC> 16 mg/L,
      10.9%; ceftazidime, MIC > 4 mg/L, 9.6%; ciprofloxacin, MIC > 1 mg/L, 8.1%;
      imipenem, MIC > 4 mg/L 2.5% and meropenem, MIC > 4 mg/L, 1.1%. Resistance to each
      antimicrobial except amikacin was commoner among the 134 isolates from patients
      in intensive care units (ICUs) than amongst the 1042 isolates from other in
      patients (P < 0.01). Resistance to penicillins and ceftazidime, though not to
      other agents, was rarer among the 797 isolates from out-patients than amongst
      those from non-ICU in-patient (P < 0.01). Compared to a similar study in 1982,
      during which 1866 isolates had been examined, the frequency of resistance to the
      aminoglycosides increased (P < 0.05) as had those to the penicillins and
      ceftazidime (P < 0.01). Ciprofloxacin and the carbapenems were not tested in
      1982. Cross-resistance patterns suggested that the increases in resistance to
      aminoglycosides and beta-lactams were largely a reflection of greater numbers of
      isolates with barrier or efflux mechanisms and were not due to an increase in
      isolates with antibiotic-degrading enzymes. The participating hospitals mostly
      employed Stokes' disc diffusion method and, when the results were compared to the
      MICs determined at the LHMC, fewer than 9% of the isolates reported as
      susceptible were found to be resistant. However, up to 72% of those reported by
      the hospitals as resistant were found to be susceptible.

PMID- 7628987
TI  - Evaluation of the in-vitro activity of furopenem (SY5555 or SUN5555) against
      respiratory tract pathogens and beta-lactamase producing bacteria.
AB  - Furopenem is a novel orally active penem. In this study, furopenem was highly
      active in vitro against Streptococcus pneumoniae (MIC90 0.03 mg/L), Haemophilus
      influenzae (MIC90, 2 mg/L), and Moraxella catarrhalls (MIC90, 0.5 mg/L). Its
      activity was not reduced by a variety of beta-lactamase enzymes, however beta 
      lactam resistance by other mechanisms was associated with higher MICs.

PMID- 7628988
TI  - In-vitro antimicrobial activity of the new fluoroquinolone, grepafloxacin,
      against pathogenic Nocardia spp.

PMID- 7628989
TI  - The susceptibility of Helicobacter pylori to the rifamycin, rifaximin.
AB  - Forty strains of Helicobacter pylori had an MIC(50) of 4 mg/L of the non
      absorbably antibiotic, rifaximin. Neither synergy nor antagonism was demonstrated
      when the drug was combined with ampicillin, metronidazole and omeprazole and the
      rate of spontaneous mutation was less than 1 in 10(8). With these in-vitro
      characteristics, rifaximin should now be assessed for clinical efficacy.

PMID- 7628990
TI  - Recommendations for the calculation of the post-antibiotic effect for beta
      lactams and gram-negative bacilli.

PMID- 7628991
TI  - Relative potencies of azithromycin, clarithromycin and five other orally
      administered antibiotics.

PMID- 7628992
TI  - Low prevalence of penicillin tolerance in group A streptococci.

PMID- 7628993
TI  - Penetration of pefloxacin and ciprofloxacin into lung tissue.

PMID- 7628994
TI  - A review of microfabricated devices for gene-based diagnostics.
AB  - The next technologic revolution may well be the miniaturization of solution phase
      experimentation through the marriage of microelectronics and molecular biology.
      Already researchers leading this rapidly emerging technology are developing
      prototype biochemical "microlaboratories" that offer a millionfold reduction of
      scale; that is, biochemical analyses are being conducted with picoliter sample
      volumes rather than conventional microliter formats. Such miniaturization is
      achieved by exploiting the well-honed tools of microelectronics that accommodate
      highly parallel automated assays, ultrasensitive detection, high throughput,
      integrated data acquisition, computation, and distributed data storage/retrieval.
      The subject of this paper is to survey this evolving bioelectronic
      miniaturization technology with applications to gene-based diagnostics. Several
      pioneering microchips are described and compared to traditional biochemical
      methods. Specifically, miniaturized examples of various diagnostic processes such
      as sample preparation (PCR), assays (electrophoresis and probe arrays), and
      detection (integrated CCDs) are presented. Although these microdevices are rather
      embryonic they represent the first steps toward fabricating a fully integrated
      diagnostic system on a microchip.

PMID- 7628995
TI  - Localization of Epstein-Barr virus in Castleman's disease by in situ
      hybridization and immunohistochemistry.
AB  - Paraffin wax sections of lymph node biopsies from a total of thirteen patients
      with the morphologic and clinical features of Castleman's disease were analyzed
      for the presence of the Epstein-Barr virus (EBV) by in situ hybridization for the
      noncoding EBV early RNAs (EBERs) and by immunohistochemistry for the EBV-encoded
      latent membrane protein-1 (LMP-1). Of twelve cases of localized Castleman's
      disease EBER-positive cells were identified in five, and in these cases were only
      rarely found and were always confined to the interfollicular regions. LMP-1 was
      not detected in any of these cases, either alone or after dual staining for EBERs
      and LMP-1. (A similar pattern of EBER expression is seen in nonneoplastic
      lymphoid tissue from EBV-positive individuals.) No EBER-positive or LMP-1
      positive cells were identified in a single case of multicentric Castleman's
      disease. In two additional patients initially diagnosed with Castleman's disease
      of localized plasma cell type, repeat biopsy showed Hodgkin's disease. In both
      cases Reed-Sternberg cells and their variants were identified in the original
      biopsy on which the diagnosis of Castleman's disease was made. In one of these
      cases these cells showed expression of EBERs and LMP-1, indicating latent
      infection with EBV. The results suggest that EBV is not generally associated with
      Castleman's disease. Further analysis of a series of cases of multicentric
      Castleman's disease is indicated.

PMID- 7628996
TI  - Chronic myeloid leukemia granulocytes exhibit reduced actin polymerization after
      chemotactic peptide stimulation.
AB  - Polymorphonuclear leukocytes (PMNL) from chronic myeloid leukemia (CML) patients
      are defective for chemotaxis in response to the synthetic chemotactic peptide n
      formyl-methionyl-leucyl-phenylalanine (fMLP) as compared to normal PMNL. The
      present study investigated whether the defective chemotactic response was
      mediated through altered actin polymerization induced with fMLP. Granulocytes
      isolated from seven normal subjects and seven CML patients were stimulated with
      fMLP and lysed with Triton containing buffer at time points of 0, 30 seconds, and
      1, 2, and 10 minutes. The Triton insoluble cytoskeleton containing polymerized
      actin was analyzed by SDS-PAGE and densitometry. The CML PMNL polymerized
      significantly lesser actin than normal PMNL on stimulation with 10 nM (p > 0.05)
      and 1 nM (p > 0.01) fMLP. This lower actin polymerization observed in fMLP
      stimulated CML PMNL may be responsible for the defective chemotaxis seen in these
      cells.

PMID- 7628997
TI  - Neutrophil functions in essential thrombocythemia.
AB  - Chronic myeloproliferative diseases, such as chronic myeloid leukemia and
      polycythemia vera, are associated with neutrophil dysfunction. Very little data
      is available on essential thrombocythemia (ET). In the current study we evaluated
      21 patients with ET. All patients were studied at least 16 weeks after any
      cytostatic therapy and 10 days after any other therapy. Neutrophil functions were
      investigated as follows: flow cytometric evaluation of whole blood phagocytosis
      of opsonized FITC-conjugated E. coli; whole blood chemiluminescence after
      stimulation with opsonized zymosan and evaluation by an automated, computer
      assisted luminometer (LB 950, Berthold); and chemiluminescence and superoxide
      anion generation by purified neutrophils after f-MLP and PMA stimulation.
      Chemiluminescence and superoxide anion generation after f-MLP stimulation were
      found to be significantly lower than in normal subjects, whereas values within
      the normal ranges were registered after PMA stimulation. Phagocytosis-associated
      chemiluminescence was found to be impaired both by using zymosan opsonized with
      autologous plasma and zymosan opsonized with normal plasma, despite a normal
      phagocytic activity. These data show the presence in ET of a complex neutrophil
      dysfunction that may be related to an impaired signal transduction during both
      the phagocytic process and f-MLP stimulation.

PMID- 7628998
TI  - Nonspecific immunostaining of blast cells of acute leukemia by antibodies against
      nonhemopoietic antigens.
AB  - It is well known that some of the widely used antibodies directed against
      hemopoietic antigens exhibit cross-reactivity with normal and neoplastic
      nonhemopoietic cells. By contrast, relatively little is known about the
      immunoreactivity of hemopoietic cells with antibodies that detect nonhemopoietic
      antigens. In this study 43 routinely processed bone marrow biopsy specimens
      containing infiltrates of acute leukemia of different subtypes were stained with
      a panel of 20 antibodies that detect nonhemopoietic antigens in formalin-fixed
      and paraffin-embedded tissue. Thirteen of the antibodies applied (KL1; BMA 120;
      and antibodies against epithelial membrane antigen, alpha-fetoprotein, prostate
      specific acid phosphatase, prostate-specific epithelial antigen, placental
      alkaline phosphatase, alpha-amylase, serotonin, bombesin, beta-human chorionic
      gonadotrophin, desmin, and S-100 protein) did not stain blast cells in any of the
      cases. However, anti-vimentin, HMB45, and anti-myoglobin stained blast cells in
      the majority of the cases; the antibodies against thyroglobulin, actin, and
      carcinoembryonic antigen stained blast cells in 10% to 25% of the cases; and anti
      neuron-specific enolase stained blast cells in less than 10% of the cases. No
      correlation was found between the leukemia subtype and the pattern of
      immunoreactivity. The staining specificity, (i.e., the specificity of binding of
      the primary antibody--immunologic vs. nonimmunologic binding), was tested by
      increasing the dilution of the primary antibody and comparing the staining
      intensity in the bone marrow specimens and control tissue. Staining specificity
      was confirmed only for staining with the antibodies against neuron-specific
      enolase and vimentin. The findings show that immunoreactivity of tumor cells in
      bone marrow biopsy specimens for nonhemopoietic antigens does not exclude a
      diagnosis of acute leukemia.

PMID- 7628999
TI  - Exercise-induced asthma in athletes: current issues.

PMID- 7629000
TI  - Exercise-induced asthma and the athlete.

PMID- 7629001
TI  - Effect of an alpha 2-adrenoceptor antagonist, midaglizole, on bronchial
      responsiveness to histamine in patients with mild asthma.
AB  - The purpose of this study was to investigate the effects of midaglizole (MID) and
      interactions of MID with beta 2-agonists on bronchial hyperresponsiveness (BHR).
      Thirteen patients with mild asthma were randomized with respect to whether they
      were taking oral beta 2-agonists, and the investigators were blinded to patients'
      regular drug regimens. Histamine challenge test was performed before and after
      oral administration of MID for 1 week (300 mg/day). There was a significant
      increase in PC20 values in asthmatic subjects on regular therapy with beta 2
      agonists (p < 0.05), whereas asthmatics not taking beta 2-agonists showed no
      significant change in PC20. These results suggest that MID may participate in
      improved BHR in the presence of beta 2-agonists and play some role in enhancing
      the effects of beta 2-agonists.

PMID- 7629002
TI  - Intractable or uncontrolled asthma: psychosocial factors.
AB  - The purpose of this study was to address the question of why, when there is a
      comparable severity of asthma, medical facilities, and treatments, some children
      develop controlled asthma whereas other children do not and are frequently ill.
      The major research questions pertained to whether families with a child with
      uncontrolled asthma differ from families with a child with controlled asthma as
      regards family characteristics and child-rearing attitudes, whether particular
      psychosocial variables relate to the severity of the asthma, and whether the
      interaction between the severity of the asthma and its controllability may
      clarify the role of psychosocial variables. Two studies were conducted, in which
      70 asthmatic children (age range 9-15 years) and their families participated. The
      children and their caregivers were presented with measures assessing parental
      child-rearing attitudes, the problem-solving abilities of the caregivers, family
      functioning, and emotional disorders in the asthmatic children. Contrary to the
      assumptions derived from the psychosomatic family model, the findings of these
      studies suggest, among other things, that cohesion of family members and rigid
      manner of function of caregivers may have a positive rather than a negative
      influence on the welfare of the asthmatic child. In addition, controlled asthma
      was found to relate to the correct use of medication, which was predominantly
      evident in more structured and interdependent family environments. Of major
      importance is the conclusion that a distinction between controlled and
      uncontrolled asthma leads to a better insight into the role of psychosomatic
      variables than a distinction on the basis of the severity of the asthma.

PMID- 7629004
TI  - Risk factors for asthmatic patients requiring intubation. I. Observations in
      children.
AB  - There are significant concerns regarding the increased mortality of patients with
      asthma. Indeed the paradox of improved pharmacotherapy but worsening prognosis
      has been explored in depth in several studies including observations in
      epidemiology, access to medical care, and drug toxicity. Because of our ability
      to track all admissions to a tertiary-care hospital, we attempted to define the
      demographic data from a population of asthmatic children admitted for asthma in
      order to identify risk factors for intubation. We performed a retrospective
      cohort study of all asthma admissions excluding patients with cystic fibrosis.
      This study included all asthmatics aged 5-12 years admitted over a 10-year period
      (1984-1994) to the University of California at Davis Medical Center, Sacramento.
      A total of 300 such asthma admissions were reviewed, involving 135 girls and 165
      boys, mean age 7.7 +/- 2.4 years. Of this group, 166 children were black, 70 were
      Caucasian, 49 were Hispanic, 14 were Asian, and 1 was an American Indian. By
      National Heart, Lung, and Blood Institute guidelines, this group included 147
      mild, 117 moderate, and 36 severe cases. Thirteen children required intubation
      for their asthma. Significant risk factors identified for children requiring
      intubation, compared to those who did not require intubation, were secondhand
      smoke exposure [odds ratio (O.R.) 22.4; 95% confidence interval (C.I.) 7.4,
      68.0], psychosocial problems (O.R. 13.5; 95% C.I. 5.1, 36.0), family dysfunction
      (O.R. 13.0; 95% C.I. 3.9, 43.9), upper respiratory infection (O.R. 10.2; 95% C.I.
      3.4, 28.1), little formal education (O.R. 8.7; 95% C.I. 2.4, 31.6), prior asthma
      emergency room visit in past year (O.R. 7.2; 95% C.I. 1.9, 27.1), prior asthma
      hospitalization in past year (O.R. 7.1; 95% C.I. 2.2, 22.2), crowding (O.R. 6.9;
      95% C.I. 2.5, 19.1), low socioeconomic status (O.R. 6.5; 95% C.I. 2.1, 20.8),
      steroid-dependent (O.R. 3.8; 95% C.I. 1.2, 12.1), parental history of allergy or
      asthma (O.R. 3.4; 95% C.I. 1.1, 10.0), and language barrier (O.R. 3.3; 95% C.I.
      1.1, 10.6). Nonsignificant mild risk factors included inhaled cromolyn (O.R. 2.7;
      95% C.I. 0.7, 10.0), atopy (O.R. 1.9; 95% C.I. 0.6, 5.9), and prior intubation
      (O.R. 1.6; 95% C.I. 0.2, 13.1). These risk parameters may be important
      determinants of baseline risk for asthma deaths and their recognition may have a
      significant impact on preventive measures.

PMID- 7629003
TI  - Conversion from twice- to once-daily extended-release theophylline treatment in
      patients with reversible airway obstruction.
AB  - This multicenter, randomized, investigator-blinded, parallel group study compared
      the effects of converting patients from a q12h extended-release theophylline
      preparation (Theo-Dur) to a q24h extended-release product (Uni-Dur). Patients (n
      = 133) first received open-label Theo-Dur treatment with dosage titrated to
      achieve peak serum theophylline concentrations of 10-20 micrograms/ml. Patients
      then were randomized to continue Theo-Dur (n = 64) or to convert to Uni-Dur (n =
      60) with peak serum theophylline concentrations maintained in the desired range.
      Pulmonary function tests were performed during the open-label and blinded
      periods; patients maintained diaries and performed peak flow measurements before
      each dose of study treatment. Adverse events were recorded throughout the study.
      Respiratory status during blinded treatment was rated as the same or improved
      compared with open-label treatment by > 87% of evaluable patients and physicians,
      regardless of treatment group. There were no significant differences in mean peak
      serum theophylline concentrations at baseline, at the final evaluation, or at any
      point during the study. Few dosage adjustments were necessary (5/52, Uni-Dur;
      9/57, Theo-Dur). There were no significant changes in pulmonary function test
      results or patient diary entries between the open-label and blinded periods.
      Headache and nausea were the most commonly reported adverse events. In
      conclusion, converting patients from twice- to once-daily theophylline treatment
      resulted in no significant changes in any measures of pulmonary function, and
      there were no significant differences between the groups during the blinded
      treatment period.

PMID- 7629005
TI  - Comparison of stayers, dropouts, and newcomers in a longitudinal population study
      of asthma and bronchial hyperresponsiveness: introduction of bias?
AB  - A random sample of children and adolescents from the general population in
      Copenhagen, Denmark, has been examined twice (6 years apart) with respect to
      asthma, allergy, and nonspecific bronchial hyperresponsiveness. To investigate
      potential bias resulting from loss of baseline subjects at follow-up (dropout
      bias) and bias resulting from subjects entering the study at the follow-up stage
      (newcomer bias), stayers (subjects who participated in both examinations) were
      compared to dropouts and newcomers, respectively. The sample consisted of 983
      subjects (aged 7-17 years at the time of the baseline study), of whom 408 (199
      boys) participated in both examinations (stayers), 119 (62 boys) in the baseline
      study only (dropouts), and 257 (124 boys in the follow-up study only (newcomers).
      Thus, a total of 784 subjects (80% of the sample) were examined either once or
      twice. At baseline dropouts did not differ from stayers with respect to
      anthropometric data, smoking habits, pulmonary function, or prevalence of
      positive skin prick tests, bronchial hyperresponsiveness, asthma, and allergic
      diseases. Likewise, these variables for newcomers were not different from those
      of the stayers apart from a significantly higher smoking rate in newcomers (45%
      vs. 32%, p = 0.003). Based on these findings and the high overall response rate,
      it seems reasonable to assume that the group of stayers is representative of the
      whole sample, apart from an underestimation of the number of smokers and,
      therefore, an underestimation of the risks associated with smoking.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7629006
TI  - Comparison of dose-response slopes obtained by simultaneous assessment of changes
      in FEV1 and transcutaneous oxygen partial pressure during methacholine challenges
      in asthmatic patients.
AB  - We aimed to ascertain whether monitoring changes in transcutaneous (tc) oxygen
      partial pressure (PO2) may be used to determine the slope of the dose-response
      curves to inhaled methacholine. In 10 adult asthmatic patients, FEV1 and tcPO2
      were simultaneously measured during inhalation of doubling methacholine
      concentrations. In each patient, the slopes of the methacholine dose-response
      curves for FEV1 and tcPO2 were similar and strongly correlated (r = 0.72; p <
      0.05). The results indicate that tcPO2 monitoring represents a useful, reliable
      tool for analysis of the slope of dose-response curves to inhaled methacholine in
      asthmatic patients. It can also be used to investigate the pathophysiological
      implications of bronchial hyperreactivity.

PMID- 7629007
TI  - Physicians' prevention-related practice behaviors in treating adult patients with
      asthma: results of a national survey.
AB  - To improve the health outcome of adults with asthma, it is important to
      understand the current practice behaviors of physicians related to the prevention
      and treatment of asthma. A national survey was conducted to ascertain the
      practice behaviors of physicians in five specialty areas: internal medicine,
      pulmonary, allergy/immunology, occupational health, and family health.
      Similarities and differences in practice among the specialty areas are indicated.
      The data provide a basis for recommendations to improve the management of asthma
      by standardizing history taking, increasing the use of pulmonary function
      testing, and using effective counseling and patient education strategies.

PMID- 7629008
TI  - Homogeneity of the pyruvate dehydrogenase multienzyme complex from Bacillus
      stearothermophilus.
AB  - The pyruvate dehydrogenase multienzyme complex was purified from Bacillus
      stearothermophilus by means of six gel-filtration column chromatographies; once
      on Cellulofine GCL-2000, twice on Sepharose CL-2B, and three times on Sephacryl S
      500HR. The molecular size distribution of the complex was examined in detail by
      gel-filtration chromatography, analytical and sucrose-density
      ultracentrifugations, and dynamic light scattering. The complex was found to be
      homogeneous; a dimeric complex was undetectable even with a high concentration of
      protein (below 6.8 mg/ml).

PMID- 7629009
TI  - Ordered structure of the crystallized bovine 20S proteasome.
AB  - Eukaryotic proteasomes are multicatalytic proteinase complexes with a molecular
      weight of 750 kDa, containing, respectively, two copies of a hetero-heptamer of
      alpha-type subunits and one of beta-type subunits, (alpha 1-7 beta 1-7)2.
      Proteasome was purified from bovine liver and crystallized into a hexagonal
      system with cell dimensions of a = b = 121.83(2) A, c = 930.68(6) A. A
      cylindrical particle size of 122 A diameter and 155 A height was determined from
      the molecular packing in a unit cell. The crystal gave diffraction spots up to at
      least 4.4 A resolution, which was the minimum spacing of the camera used. The
      overall temperature factor of the enzyme was estimated to be in the range of 36.2
      to 25.8 A2. These results imply that the enzyme complex has a unique ordered
      structure comprising multisubunits with two types of hetero-heptamer. This
      ordered structure may facilitate highly organized cooperation of individual
      functions of subunits within the enzyme complex.

PMID- 7629010
TI  - An improved method for extraction of mRNA and protein from the fungus Chaetomium
      gracile with anhydrous hydrogen fluoride.
AB  - We previously reported that DNAs directly applicable to restriction analyses and
      transformation of Escherichia coli can be extracted from fungi and yeasts by use
      of anhydrous hydrogen fluoride (HF) under a mild condition, 5 min at 0 degrees C
      [Oshiro, S., Katsura, N., Kitada, K., and Gunge, N. (1987) FEBS Lett. 220, 383
      386]. In the present investigation, we examined whether this improved method is
      also applicable to extraction of RNA and protein from the fungus Chaetomium
      gracile. The RNA and protein were effectively extracted from the fungus after
      anhydrous hydrogen fluoride (HF) treatment for a short time (1 min) at 0 degrees
      C. The extracted poly(A)-enriched mRNA and proteins were fully intact: the mRNA
      purified by messenger-activated paper with poly(U) directed not only the
      incorporation of [3H]glycine into polypeptides but also the synthesis in a rabbit
      reticulocyte lysate cell-free system of proteins reactive to antibodies against
      the soluble fraction extracted from the fungus by HF. Analyses by gel filtration
      and polyacrylamide electrophoresis under native conditions showed that dextranase
      extracted from the fungus by HF under the same conditions had the same molecular
      weight and electrophretic mobility as the enzyme excreted into the medium. This
      suggests that the mRNAs and proteins extracted by this method are also applicable
      to protein synthesis directed in a cell-free system and to enzyme purification
      from a fungus insusceptible to lytic enzymes. This method provides a pure
      preparation of mRNA within 5 h and starting materials for protein purification
      within 1 h.

PMID- 7629011
TI  - A strategy for testing the suitability of cysteine replacements in dihydrofolate
      reductase from Escherichia coli.
AB  - Amino acid sequences in proteins can contain residues which complicate
      biochemical, biophysical, or protein engineering studies but which are not
      essential for folding or activity. Their replacement with other naturally
      occurring amino acids which are not subject to such complications but which
      maintain essential properties of the protein is a desirable goal. A simple
      strategy for testing various mutants for their suitability is described for a
      pair of cysteine residues in dihydrofolate reductase (DHFR) from Escherichia
      coli. Using a reconstructed gene which preserves the amino acid sequence and
      introduces a variety of unique restriction sites, the cysteines at positions 85
      and 152 were replaced by site-directed and cassette mutagenesis. The enzymatic
      activity, stability, and folding mechanism of six double mutant DHFR proteins
      were examined with the purpose of identifying a suitable alternative to wild type
      DHFR. The Cys85-->Ala and Cys152-->Ser double mutant DHFR was found to retain the
      four channel folding mechanism and have activity and stability which are
      comparable to the wild type enzyme. The replacement of the cysteines improved the
      resistance of DHFR to the irreversible loss of activity at high temperature.

PMID- 7629012
TI  - Dimeric chemotactic peptides discriminate between chemotaxis and superoxide
      production of human neutrophils.
AB  - A series of dimeric fMLPs were synthesized by cross-linking with hydrophilic
      linkers, mono-, di-, tri-, and tetraethylene glycols. All of the dimers showed
      higher activities than monomeric fMLP in chemotaxis assays for human neutrophils.
      The magnitude of the activity enhancement was dependent on the linker length. On
      the other hand, production of superoxide anion was not as enhanced as chemotaxis.
      The experimental results indicate that these dimers, especially the triethylene
      glycol-bridged fMLP dimer, D-fMLP-G3, are selective agonists for chemotaxis. In
      order to distinguish between biological activities and intracellular signaling,
      rapid mobilization of the intracellular calcium was also measured. D-fMLP-G3
      strongly enhanced the calcium mobilization. These results suggest that chemotaxis
      was correlated with the increase of the intracellular calcium concentration,
      whereas NADPH oxidase was not activated to generate superoxide by this elevation
      of cytoplasmic calcium caused by the dimeric ligand, D-fMLP-G3. The dimeric fMLPs
      might act as useful ligands for studying the intracellular signaling mechanisms
      of human neutrophils.

PMID- 7629013
TI  - In vivo effect of GroESL on the folding of glutamate racemase of Escherichia
      coli.
AB  - The overexpression of the murI (glr) gene, which encodes the glutamate racemase
      of Escherichia coli, resulted in the formation of inclusion bodies of the enzyme,
      and little activity was found in the soluble fraction of the transformant cells.
      The coexpression of the groESL gene with murI caused an in vivo solubilization of
      glutamate racemase in an active form. We isolated the active enzyme and purified
      it effectively.

PMID- 7629014
TI  - Structure and regulation of the chicken GATA-3 gene.
AB  - To elucidate the mechanisms underlying the tissue-restricted expression of GATA
      factor transcription, we have isolated and analyzed the genomic chicken GATA-3
      (cGATA-3) locus. Structural analysis of the clones showed that the cGATA-3 gene
      consists of six exons which span more than 19 kb. Two trans-activating domains
      and two Zn finger domains of cGATA-3 were found to be encoded separately by exons
      2/3 and 4/5, respectively, indicating that each functional domain of GATA-3 is
      encoded by a discrete exon. We have determined 1.7 kb of upstream promoter
      sequence and found a number of sequence motifs which match those of known
      transcription factor binding sites. Activities of presumptive regulatory regions
      of this gene were assessed by transfecting chimeric constructs into a chicken T
      cell line MSB-1. The results showed three features of cGATA-3 gene regulation.
      The basal promoter activity of the cGATA-3 gene is determined by sequences lying
      between -104 and -29 bp of the promoter region. The upstream region containing
      the GATA and CACCC elements in close proximity (-1280 to -1152) appeared to act
      as a negative transcriptional regulator, whereas the region -1151 to -850 acts as
      a positive regulator. Thus, the expression of cGATA-3 gene is under complex
      regulation and the mode of regulation of cGATA-3 gene expression is suggested to
      be different from that of GATA-1 genes.

PMID- 7629015
TI  - Reversible effects of okadaic acid and microcystin-LR on the ATP-dependent
      interaction between actin and myosin.
AB  - Okadaic acid, a toxin from black sponge, and microcystin-LR, a toxin from blue
      green algae, were found to stimulate and inhibit, respectively, the actin
      activated ATPase activity of skeletal muscle myosin. These effects were confirmed
      by monitoring the sliding movement of actin-filaments on myosin. This technique
      also enabled us to demonstrate the reversibility of these effects, a property
      that is essential for their use as a pharmacological tool for the analysis of the
      mechanochemical characteristics of muscular contraction. The sites of action of
      both toxins were within the myosin molecule, as demonstrated by monitoring (i)
      their effects on the intrinsic tryptophan fluorescence of heavy meromyosin and
      (ii) their ATP-dependent effects on the ATPase activity. The former effects
      further suggest that myosin heads are their actual sites of action, and the
      latter effects suggest that they interact with the ATPase active sites located
      within the heads.

PMID- 7629016
TI  - Proton exchange and basepair kinetics of yeast tRNA(Phe) and tRNA(Asp1).
AB  - Nuclear magnetic resonance measurements of proton exchange were performed on
      yeast tRNA(Phe) and yeast tRNA(Asp), at temperatures from 20 to 45 degrees C, in
      the presence of various levels of salt, phosphate, added magnesium, and pH. The
      dynamical changes of the tRNA molecule were interpreted, with the aid of firmly
      established assignments and the use of the saturation recovery technique. In
      tRNA(Phe), the exchange rates in zero magnesium indicated early melting of the
      acceptor stem, tertiary structure, and D stem. However, in the presence of even
      low levels of magnesium the D stem remained intact up to high temperature,
      stabilized by a Mg2+ ion. A similar unfolding sequence was observed in tRNA(Asp).
      The difference between these two tRNAs was the thermal behavior of the tertiary
      resonance U8-A14. In tRNA(Phe), this base pair showed sharp rate increases
      between 32 and 39 degrees C. However, in tRNA(Asp), it remained intact up to 36
      degrees C and disappeared at 39 degrees C, even if there was not important
      kinetic broadening. By measuring the temperature dependence of the exchange
      rates, we obtained an activation energy of 40-60 kcal/mol for all the imino
      protons of yeast tRNA(Phe) in zero magnesium. The same activation energy was
      obtained for tRNA(Phe) with equimolar concentration of magnesium. By
      investigation of the dependence of the exchange rates of these imino protons on
      solution conditions, we observed the transition from kop rate limiting in the
      absence of magnesium to kex rate limiting in the presence of magnesium.

PMID- 7629017
TI  - Preparation and characterization of the hydrophilic CuA-cytochrome c domain of
      subunit II of cytochrome c oxidase from thermophilic bacillus PS3.
AB  - Cytochrome c oxidase of the thermophilic bacterium, PS3, was treated with
      trypsin. The hydrophilic domain of 26 kDa can be easily cleaved off from the
      hydrophobic anchor domain at the N-terminal region of subunit II, but remains
      attached to the rest of the enzyme upon gel-filtration in the presence of 0.2%
      lauroyl sarcosinate. The separation occurred in the presence of 5 M urea in
      addition to 0.2% lauroyl sarcosinate. After relatively prolonged proteolysis,
      that induced severe activity decay, and subunit I fragmentation, the 26 kDa
      fragment of subunit II can be easily isolated from the rest, suggesting that this
      fragment with cytochrome c and CuA interacts with subunit I. The separated
      fragment showed absorption spectra due to CuA and cytochrome c. Reconstitution of
      the cytochrome oxidase activity occurred on addition of the 26 kDa fragment to
      the proper gel-filtration chromatographic fraction.

PMID- 7629018
TI  - Protein factors required for in vitro transcription of Sendai virus genome.
AB  - To elucidate the mechanism of transcription and replication of Sendai virus, we
      developed an efficient and faithful in vitro transcription system using purified
      virus particles. The in vitro RNA synthesis was almost entirely dependent on the
      addition of eukaryotic cell extracts, including those from various cultured
      mammalian cells, mammalian tissues, and even from plant cells. The RNA products
      were almost identical to authentic mRNA species synthesized in the infected
      cells, in their size distribution, the presence of 3'-poly(A) tail and the
      presence of methylated 5'-cap structure (m7GpppAm). Ribonuclease protection
      experiments after annealing the in vitro RNA with viral genomic RNA (vRNA)
      indicated that the virion-associated RNA-dependent RNA polymerase transcribes
      correct regions of the RNA genome in vitro. The active component(s) that is
      required for Sendai virus mRNA synthesis was partially purified from bovine brain
      and was separated into at least two complementary fractions, one of which could
      be replaced by highly purified cellular tubulin. When viral ribonucleoprotein
      complexes were used instead of virus particles in the in vitro transcription,
      only Sendai virus-infected cell extracts supported mRNA synthesis, and extracts
      from uninfected cells or cells infected with other viruses were found to be
      inert. These results suggest that, in addition to the general factors which are
      present ubiquitously in eukaryotic cells, a factor(s) specific to Sendai virus
      infection is required for Sendai virus transcription.

PMID- 7629019
TI  - Leader peptidase from Escherichia coli: overexpression, characterization, and
      inactivation by modification of tryptophan residues 300 and 310 with N
      bromosuccinimide.
AB  - We have overproduced the leader peptidase from Escherichia coli in a high yield
      by using a T7 RNA polymerase/promoter system and purified the enzyme. This leader
      peptidase showed an apparent pH optimum of about 10 toward a synthetic peptide
      substrate, and was stable at temperatures below 40 degrees C. Kinetic studies
      indicated that one of the active site residues in the enzyme has a pKa value of
      approximately 7.5. The enzyme was rapidly inactivated by reaction with N
      bromosuccinimide (NBS). When approximately two tryptophan residues were oxidized
      with NBS, the activity was almost completely lost and this inactivation was
      markedly prevented by a substrate. These NBS-reactive tryptophan residues were
      identified as Trp300 and Trp310 by a peptide mapping analysis. This indicates
      that Trp300 and/or Trp310 are critically important for the activity of the leader
      peptidase. On the other hand, the enzyme was scarcely inhibited by treatment with
      N-acetylimidazole, iodoacetic acid, 5,5'-dithiobis(2-nitrobenzoic acid), succinic
      anhydride, or 2,4,6-trinitrobenzenesulfonate. Diethylpyrocarbonate inhibited the
      enzyme; however, this inhibition did not seem to result from the modification of
      histidine residues. Thus, there seem to be no functionally important tyrosine,
      cysteine, or histidine residues or amino groups among the residues which readily
      react with these reagents. However, the enzyme was inactivated significantly by
      treatment with phenylglyoxal or 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide.
      Therefore, some of the arginine residues and the carboxyl groups appear to be
      important for the enzyme activity.

PMID- 7629020
TI  - Structures of cDNAs encoding the muscle-type and non-muscle-type isozymes of
      lamprey fructose bisphosphate aldolases and the evolution of aldolase genes.
AB  - Nearly full-length cDNA clones for muscle-type and non-muscle-type aldolase mRNAs
      were cloned from lambda gt10 cDNA libraries constructed from skeletal muscle and
      liver mRNAs of lamprey (Entosphenus japonicus). The cDNA-M8 has 2,240 bp carrying
      an open reading frame of 1,089 bp which encodes 362 amino acids without the amino
      terminal methionine, while the cDNA-L3 is 1,761 bp in length and has an open
      reading frame of 1,092 bp, which encodes 363 amino acids without the methionine.
      We designated the cDNA clones M8 and L3 as the muscle-type and non-muscle-type
      aldolase cDNAs, respectively. The entire amino acid sequences deduced from cDNA
      M8 and -L3 show a high degree of identity to one another (76%) and also to
      vertebrate aldolases A (74-76%), B (68-70%), and C (71-76%) and Drosophila
      melanogaster aldolases alpha, beta, and gamma (66-67%). Northern blot analyses
      using the 3'-noncoding sequences of cDNA-M8 and -L3 as hybridization probes
      indicated that the muscle-type mRNA is expressed mainly in the skeletal muscle,
      heart muscle, brain, and some other tissues, but probably not in liver, while the
      non-muscle-type mRNA is expressed mainly in the liver and also in brain and other
      tissues, except for the heart muscle. Phylogenetic analyses showed that both
      muscle-type and non-muscle-type aldolases of lamprey resemble one another and
      might share a common ancestor with vertebrate aldolases A and C, but they are not
      direct ancestors of vertebrate aldolases.

PMID- 7629021
TI  - Chicken alpha-enolase but not beta-enolase has a Src-dependent tyrosine
      phosphorylation site: cDNA cloning and nucleotide sequence analysis.
AB  - Chicken alpha- and beta-enolase cDNAs have been cloned and analyzed to reveal
      that alpha- but not beta-enolase has a Src-dependent phosphorylation site. The
      deduced amino acid sequence of the chicken alpha-enolase showed more than 90%
      homologies with those of other vertebrate alpha-enolases including amphibian
      (Xenopus laevis) alpha-like enolase. The chicken beta-enolase, on the other hand,
      shares 84-85% amino acid sequence homology with mammalian beta-enolases. These
      chicken enolases also showed more than 70% sequence identity with an insect
      (Drosophila melanogaster) enolase and around 60% with two yeast enolases. The
      amino acid sequence between residues 33 and 50 in chicken alpha-enolase coincided
      with the reported tryptic peptide sequence of rabbit beta-enolase, the tyrosine
      residue in which was phosphorylated in vitro by Rous-sarcoma-virus tyrosine
      kinase. The present finding suggested that the tyrosine residue at position 44 in
      chicken alpha-enolase is the phosphorylation site by the tyrosine kinase. In
      chicken beta-enolase, on the other hand, the corresponding tyrosine residue was
      found to be replaced with a histidine residue, in accordance with the previous
      observation that chicken beta-enolase was not phosphorylated in vivo or in vitro.
      Northern blot analysis indicated that alpha-enolase mRNA can be expressed in a
      wide range of chicken tissues, and that the gene expression switch from alpha to
      beta-enolase occurs just after hatching in developing chicken muscle.

PMID- 7629022
TI  - Interaction of the fragments characteristic of bactenecin 7 with phospholipid
      bilayers and their antimicrobial activity.
AB  - Bactenecin 7 (Bac7), a cationic polypeptide from large granules of bovine
      neutrophils, exhibits antimicrobial activity mainly against Gram-negative
      bacteria. This peptide is characterized by high contents of Arg and Pro and by a
      unique sequence with an Arg-clustered region and three tandem repeats. In order
      to investigate the structure-function relationship of Bac7, two peptide
      fragments, which correspond to residues 1-17 (RRIRPRPPRLPRPRPRP, an Arg-clustered
      region) and 46-59 (LPFPRPGPRPIPRP, one of three tandem repeats), respectively,
      were synthesized. Circular dichroism (CD) measurements of the two fragments
      indicated that they took particular conformations, although these were not
      defined. These peptides can bind to acidic phospholipid bilayers without marked
      conformational changes. When acidic phospholipid bilayers entrapping 5,6
      carboxyfluorescein were treated with the peptides, no trace of the dye leaked
      out, indicating that the peptides lack the ability to disrupt lipid membranes.
      Fragment 1-17 showed weak antimicrobial activity against several bacteria, but
      fragment 46-59 was almost inactive. The present results suggest that longer
      fragments or the entire molecule of Bac7 may be required for full expression of
      antimicrobial activity and that Bac7 may manifest its activity by a
      bacteriostatic rather than a bacteriolytic mechanism.

PMID- 7629023
TI  - Solution structure of cysteine-rich domain of protein kinase C alpha.
AB  - The three-dimensional structure of the second cysteine-rich domain of protein
      kinase C alpha (residues 95-159) was determined in aqueous solution by two
      dimensional proton nuclear magnetic resonance and simulated annealing based
      calculations. On the basis of 687 distance constraints derived from assigned
      nuclear Overhauser effect (NOE) connectivities, a total of 10 converged
      structures were obtained from 40 runs of calculations. The atomic root-mean
      square (RMS) difference about the mean coordinate positions (excluding residues 1
      7, 16-17, 30-34, and 55-65) is 0.55 A for backbone atoms (N, C alpha, C') and
      1.07 A for all non-hydrogen atoms. The molecular scaffold is maintained by triple
      stranded and double-stranded twisted beta-sheets packed against an alpha-helix
      and two independent zincs are coordinated by His8, Cys38, Cys41, Cys57 and Cys21,
      Cys24, His46, Cys49, respectively. It should be noted that the metal ligands from
      the two sites are interleaved and this is thought to be a new structural motif of
      a zinc finger domain. Based on the resultant structure, we propose an interaction
      site of the cysteine-rich domain of protein kinase C with diacylglycerols and
      phorbol esters.

PMID- 7629024
TI  - Crystal structure determination of a flavoprotein FP390 from a luminescent
      bacterium, Photobacterium phosphoreum.
AB  - The three-dimensional structure of a flavoprotein, FP390, purified from a
      luminescent bacterium, Photobacterium phosphoreum, has been determined at 3 A
      resolution by X-ray crystallography. Crystallographic refinements of the
      structural model have led to an R-factor of 0.24 for the intensity data between 6
      to 3 A resolution collected with synchrotron radiation. It was found that a
      homodimer of the FP390 molecules related by a non-crystallographic 2-fold axis is
      comprised in the asymmetric unit. Two homodimers are arranged around a
      crystallographic 2-fold axis to form a tetrameric assembly. The monomer molecule
      of FP390, to which two molecules of the flavin cofactor (Q-flavin) are bound,
      consists of a seven-stranded parallel beta-sheet which forms a half of the beta
      barrel structure and seven alpha-helices which surround one side of the beta
      barrel. We suggest that the reason why the Q-flavin sample prepared from FP390 is
      always a mixture of two components is connected with the fact that the monomer
      molecules has two flavin binding sites, at the dimer interface and at the
      molecular surface.

PMID- 7629025
TI  - Identification of a lysine residue in the NADH-binding site of salicylate
      hydroxylase from Pseudomonas putida S-1.
AB  - Salicylate hydroxylase from Pseudomonas putida S-1 was irreversibly inactivated
      by trinitrobenzenesulfonic acid (TNBS). The reaction was linearly dependent on
      TNBS concentration and the second-order rate constant was 120 M-1.min-1 for the
      holoprotein at pH 8.5. Modification of one mole of lysine residue per mole of
      enzyme caused a large loss of the activity, and the enzyme was no longer able to
      show NADH-dehydrogenase activity after uncoupling. The presence of NADH, NAD+,
      ATP, or AMP afforded protection against the inactivation. The enzyme modified at
      a single lysine residue was isolated by hydrophobic chromatography as an
      apoprotein form and characterized. It could bind FAD with the same Kd value for
      that of native apoprotein. The apparent Michaelis constant of the enzyme was
      increased 13-fold for NADH, but not for salicylate. Vmax for NADH oxidation was
      decreased to one-fifth of that of the native enzyme. A peptide containing one
      trinitrophenyl-lysine residue was isolated from the chymotryptic digest of the
      modified enzyme and its amino acid sequence was determined to be TADVAIAADGIKSSM,
      which is homologous to the sequence from R-154 to I-168 of salicylate hydroxylase
      from P. putida PpG7. The lysine in the peptide may represent a basic residue
      interacting with an anionic group of NADH in the binding site of the enzyme.

PMID- 7629026
TI  - Heparin-induced release of extracellular-superoxide dismutase form (V) to plasma.
AB  - Extracellular-superoxide dismutase [EC 1.15.1.1] (EC-SOD) is a secretory,
      tetrameric glycoprotein. A prominent feature of EC-SOD is its affinity for
      heparin. This enzyme in serum is heterogeneous with regard to heparin-affinity
      and can be divided into five fractions (I) to (V) by heparin-HPLC, whereas
      fibroblast-secreted EC-SOD consists mainly of form (V). An intravenous injection
      of 50 i.u. of heparin/kg body weight into two healthy volunteers led to an
      immediate rise of serum EC-SOD level by 2.4-2.8-fold. Only form (V), which was a
      minor component in pre-heparin serum, was increased by the intravenous injection.
      The half-life of serum EC-SOD after the prompt rise was about 90 min. The in vivo
      experiment using rats and an in vitro experiment strongly suggested the EC-SOD
      released into the plasma reconstituted the interaction with glycocalyx on the
      vascular endothelial cell surface in accordance with the elimination of heparin
      from the vascular system.

PMID- 7629027
TI  - Functional consequences of substitution of the disulfide-bonded segment, Cys127
      Cys150, located in the extracellular domain of the Na,K-ATPase beta subunit:
      Arg148 is essential for the functional expression of Na,K-ATPase.
AB  - The Cys127-Cys150 disulfide-bonded loop (L1) of the Torpedo californica Na,K
      ATPase beta 1 subunit was substituted with the corresponding loop of the rat beta
      1, mouse beta 2, or pig H,K-ATPase beta subunit. All the substituted mutant beta
      subunits assembled with the Na,K-ATPase alpha subunit in a trypsin-resistant
      manner. The mutants with L1 from the Na,K-ATPase beta subunit isoforms (rat beta
      1 and mouse beta 2) each formed a functional complex with the Na,K-ATPase alpha
      subunit. On the other hand, the complex of the alpha subunit with the mutant beta
      subunit that was substituted with the pig H,K-ATPase beta subunit L1 was inactive
      as to ATP hydrolysis. Ser131 and Phe148 located within L1 of the pig H,K-ATPase
      beta subunit-substituted mutant were back-mutated to Pro131 and Arg148,
      respectively. The Phe148 to Arg mutation restored the ability of the mutant beta
      subunit substituted with the H,K-ATPase beta subunit L1 to form a functional
      complex with the alpha subunit. These results suggested that the Cys127-Cys150
      loop of the Na,K-ATPase beta 1 subunit, especially Arg148, plays a critical role
      in the functional expression of Na,K-ATPase.

PMID- 7629029
TI  - An X-ray diffraction study on a single frog skinned muscle fiber in the presence
      of vanadate.
AB  - Using a technique to obtain a detailed X-ray diffraction pattern from a single
      frog skinned muscle fiber with synchrotron radiation and an imaging plate, we
      studied the arrangement of myosin heads to which ADP and vanadate are bound. The
      presence of 1 mM vanadate during contraction caused trapping of ADP and vanadate
      on the myosin head. Both in the presence and absence of Ca2+, the intensities of
      the equatorial reflections indicated that most of the heads with ADP and vanadate
      were located close to the backbone of the thick filament. The presence of the
      first myosin layer-line at 43 nm-1 also suggested that the heads formed a helix
      around the shaft of the thick filament. Weak intensity of actin layer-lines
      suggested that the myosin heads were detached from the thin filament. The results
      suggest that the myosin-ADP-vanadate complex has a weak affinity toward actin
      regardless of the state of the regulatory system on the thin filament.

PMID- 7629028
TI  - Characterization of serum proteins down-regulated by peroxisome proliferators:
      transient repression of apoE gene expression in the rat liver.
AB  - The effects of peroxisome proliferators on the levels of rat serum proteins were
      examined. The proliferators reduced the levels of several proteins in various
      ways with respect to proliferator-specificity and the time courses of the
      changes. The identification of three proteins by amino acid sequencing showed
      that they were functionally unrelated. This diversity suggests that several
      primary and secondary effects of the peroxisome proliferators caused the various
      changes in the levels of several serum proteins. Among these, apolipoprotein E
      was the most but transiently down-regulated by the two proliferators tested.
      Northern blots of the rat liver mRNA suggested that the primary step of the down
      regulation was at pre-translation.

PMID- 7629030
TI  - A subtilisin inhibitor produced by Streptomyces bikiniensis possesses a glutamine
      residue at reactive site P1.
AB  - We determined the complete amino acid sequence of a novel subtilisin inhibitor,
      SIL15, which had been isolated from the culture supernatant of Streptomyces
      bikiniensis and shown to be a member of the Streptomyces subtilisin inhibitor
      (SSI)-like (SIL) protein family, and then identified its reactive site. SIL15 is
      composed of 113 amino acids and exists as a dimer. Compared with other SSI-family
      inhibitors, SIL15 was found to be unique in that it possesses a Gln residue at
      the P1 site of the reactive site and has two-residue insertions in two regions,
      one in the alpha 1-helix and the other in the flexible loop region near the
      reactive site. Inhibition of subtilisin BPN' by SIL15 (inhibitor constant, 2.7 x
      10(-11) M) was due to the presence of a Gln residue at the P1 site, which was
      well consistent with the results obtained for P1-site mutants of SSI and turkey
      ovomucoid domain 3.

PMID- 7629032
TI  - Cadmium-113 NMR studies of bovine and human alpha-lactalbumin and equine
      lysozyme.
AB  - The high-affinity calcium-binding sites of bovine and human alpha-lactalbumin as
      well as equine lysozyme were analyzed by 113Cd NMR spectroscopy. In the case of
      equine lysozyme, the addition of isotopically enriched 113Cd2+ results in a
      signal at delta = -75.9 ppm corresponding to the metal ion bound to the lone
      Ca(2+)-binding site of the protein. A peak at virtually the identical resonance
      position (delta = -77.1 ppm) was observed in the analogous experiment with bovine
      alpha-lactalbumin. In addition, a signal upfield of these (delta = -94.7 ppm) was
      observed for 113Cd(2+)-substituted human alpha-lactalbumin. The chemical shifts
      of these proteins are in the vicinity of those reported for other Ca(2+)-binding
      proteins. The field dependence of the 113Cd signals for all three proteins and
      bovine calmodulin were compared. At each field, the 113Cd signal linewidths for
      the alpha-lactalbumins and the lysozyme are somewhat broader than those observed
      for the EF-hand protein. In addition, the 113Cd linewidths for the lactalbumins
      and the lysozyme, especially bovine alpha-lactalbumin, increase dramatically with
      the square of the magnetic field strength, indicative of the presence of nuclear
      relaxation via chemical shift anisotropy and chemical exchange. The protein-bound
      113Cd signals for the alpha-lactalbumins are also markedly affected by changes in
      the amount of K+ present, since Cd2+ and K+ can compete for occupation of the
      high-affinity Ca(2+)-site. Their linewidths also to some extent depend on the
      concentration of the protein itself.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7629031
TI  - Overexpression of Pseudomonas putida catechol 2,3-dioxygenase with high specific
      activity by genetically engineered Escherichia coli.
AB  - The cloned xylE gene encoding catechol 2,3-dioxygenase (metapyrocatechase) from
      TOL plasmid in Pseudomonas putida mt-2 has been expressed in Escherichia coli
      W3110 to a level of approximately 15% of the total soluble protein. Of the total
      iron in the crude extract, 45% was on the enzyme. The crystallized enzyme from E.
      coli had higher iron content (3.7 mol/mol enzyme) and specific activity (536
      U/mg) than the enzyme from P. putida mt-2. However, no differences were observed
      in physicochemical, protein-chemical, and kinetic properties between the two
      enzymes. The enzyme was a homotetramer, and no changes were observed in the
      values of M(r) (136,000 +/- 5,000) and Stokes radius (4.26 nm) in the
      concentration range from 0.36 nM to 2.8 microM, indicating that the native enzyme
      neither dissociated into subunits nor polymerized in this range. The catalytic
      center activity and the Km values for catechol and dioxygen were 278 s-1, 1.87
      and 7.45 microM, respectively, at pH 7.5 and 25 degrees C. The enzyme showed a
      broad substrate specificity. Among substrates, 4-methylcatechol and 4
      chlorocatechol showed specificity constants (approximately 200 microM-1.s-1)
      higher than that for catechol. Acetone and phenol derivatives competitively
      inhibited the activity against catechol. The relationship between specific
      activity and iron content was not linear, suggesting some conformational changes
      in the partially iron-depleted enzyme.

PMID- 7629033
TI  - Effects of alcohols on the hydrolysis of colominic acid catalyzed by
      Streptococcus neuraminidase.
AB  - Regulation of the activity of neuraminidase of Streptococcus sp. (group K) was
      evaluated by examining the effects of alcohols on the hydrolysis of colominic
      acids catalyzed by the neuraminidase. Two kinds of alcohol binding site,
      activation and inhibition sites, were proposed to exist. Competitive inhibition
      was observed with alcohols smaller than polyethylene glycol #300 (average
      molecular weight: 300), so the inhibition site is considered to be the substrate
      binding site, the size of which was estimated to be 10 A in diameter. On the
      contrary, polyethylene glycols larger than this size activated the enzyme by 1.5
      1.8 times. The activity could be raised by binding of the polyethylene glycols to
      the activation site. This activation was shown to be due solely to the decrease
      in the Michaelis constant, Km. The smaller polyethylene glycols (#200 and #300)
      were also considered to bind to the activation site, although activation was not
      clearly observed due to compensation with inhibition. Strong substrate inhibition
      by colominic acid was also observed. The activity of Streptococcus neuraminidase
      was shown to be regulated intricately by the substrate colominic acid and
      alcohols contained in the reaction medium.

PMID- 7629034
TI  - Stabilization of lysozyme against irreversible inactivation by suppression of
      chemical reactions.
AB  - The effects of additives on the nonenzymatic deamidation of an Asn residue in a
      peptide and racemization of Asp and/or Asn in lysozyme were investigated at pH 6
      and 100 degrees C. These chemical reactions were accelerated by the addition of
      phosphate ions. Several salts suppressed the deamidation in the presence of
      phosphate ions, while the salts did not affect the deamidation in the absence of
      phosphate ion at pH 6 and 100 degrees C. The results indicated that the effect of
      the salts was due to the suppression of phosphate catalysis. On the other hand,
      trifluoroethanol (TFE), which induces the conversion of random coiled
      polypeptides to secondary structured ones, dramatically suppressed the
      deamidation of an Asn residue in a peptide. The rate of deamidation in the
      presence of TFE was comparable to that of asparagine (free amino acid), which was
      very slowly deamidated. Because TFE could not suppress the deamidation of free
      asparagine, the suppression of the deamidation of an Asn residue in a peptide was
      attributed to suppression of the catalysis by the peptide bond in the carboxyl
      terminus. Since the inactivation of lysozyme was caused by multiple chemical
      reactions such as the deamidation and racemization, it was expected that the
      inactivation of lysozyme could be prevented by the addition of salts or TFE.
      Thus, it was confirmed that salts and TFE suppressed the lysozyme inactivation at
      pH 6 and 100 degrees C.

PMID- 7629035
TI  - Cleavage of bovine mitochondrial ATPase inhibitor with endopeptidases, and
      binding of the resulting peptides to the interface between the alpha- and beta
      subunits of F1ATPase.
AB  - Mitochondrial ATPase inhibitor binds to F1ATPase, forming an equimolar complex
      with the enzyme, and the binding site has been reported to be located in the beta
      subunit [Klein, G. et al. (1980) Biochemistry 19, 2919-2925] or at the interface
      between the alpha- and beta-subunits of the enzyme [Mimura, H. et al. (1993) J.
      Biochem. 113, 350-354]. In the present study, bovine ATPase inhibitor as well as
      three peptide fragments of the inhibitor, Gly1-Asn51, Glu52-Asp84, and Lys46
      Asp84, were used to examine the features of the binding of the inhibitor and
      F1ATPase. Only the amino terminal fragment, Gly1-Asn51, exhibited a similar level
      of inhibitory activity to that of the native ATPase inhibitor. Although the other
      two carboxyl terminal side fragments did not exhibit any inhibitory activity,
      they interfered with the action of the intact ATPase inhibitor when they were pre
      loaded to F1ATPase. Since the two carboxyl fragments did not interfere with the
      inhibitory action of the amino fragment, it is inferred that the inhibitor
      interacts with F1ATPase at its carboxyl terminal region prior to binding at the
      amino terminal region of the enzyme. Cross-linking experiments revealed that
      ATPase inhibitor bound to the alpha- and beta-subunits of F1ATPase, and that the
      amino terminal peptide preferentially bound to the alpha-subunit and the carboxyl
      terminal peptides to the beta-subunit.

PMID- 7629036
TI  - Distinct effects of saturated fatty acids on protein kinase C subspecies.
AB  - The effects of saturated fatty acids on the protein kinase C family were studied.
      Saturated fatty acids with carbon chain lengths of C12 to C14 activated the alpha
      , beta-, gamma-, and epsilon-subspecies, and this activation was synergistic with
      that by diacylglycerol. Tridecanoic acid (C13) was most effective among the
      saturated fatty acids examined. Saturated fatty acids having carbon chain lengths
      of less than C10 were inert, and fatty acids with longer carbon chain lengths,
      such as C16 and C18, showed little effect. In contrast, fatty acids were almost
      inactive toward the delta-subspecies, and rather inhibited its activity in the
      presence of phosphatidylserine and diacylglycerol. Phorbol ester enhanced the
      activity of the alpha-, beta-, and gamma-subspecies when added with fatty acids;
      however, it suppressed the activity of the epsilon-subspecies in the presence of
      fatty acids. Saturated fatty acids having different effects on protein kinase C
      subspecies may be useful as tools for studying the mechanism and role of protein
      kinase C activation.

PMID- 7629037
TI  - Protease II from Moraxella lacunata: cloning, sequencing, and expression of the
      enzyme gene, and crystallization of the expressed enzyme.
AB  - A gene coding for protease II (basic amino acid specific oligoendopeptidase) from
      Moraxella lacunata was cloned and expressed in Escherichia coli DH1. The
      transformant harboring a hybrid plasmid, pMPROII-12, with a 3.0-kbp insert at the
      PvuII-SacI site in pUC19, showed 23-fold higher enzyme activity than M. lacunata.
      The expressed enzyme from E. coli DH1/pMPROII-12 was purified by 40-80% ammonium
      sulfate fractionation, chromatography on DEAE-Toyopearl, and Sephadex G-150 gel
      filtration. The enzyme was most active at pH 6.5 and stable at pH 6.5-9.5. It had
      an optimum temperature of 35 degrees C for 5 min of reaction and was stable to up
      to 35 degrees C for 30 min at pH 7.0. Its molecular weight was estimated to be
      80,000 by SDS-PAGE and gel-filtration analyses. It enzyme was inhibited by
      diisopropyl fluorophosphate (DFP) and classified as a serine endoprotease. Its
      amino acid sequence was 38% homologous to that of the E. coli protease II. By
      alignment with other members of the prolyl endopeptidase family, the amino acid
      residues involved in the catalytic triad were deduced to be Ser-534, Asp-619, and
      His-654. The enzyme was crystallized by the hanging drop vapor diffusion method
      using PEG 4000 as precipitant.

PMID- 7629038
TI  - Sexual dimorphism of lipids in Harderian glands of golden hamsters.
AB  - The Harderian gland of golden hamsters excretes alkyldiacylglycerol (ADG), the
      fatty acid and alkyl compositions of which differ between males and females. ADG
      in males contains mostly straight chain fatty acids, even- and odd-numbered, the
      major one being 15:0, while ADG in females contains iso- and anteiso-branched
      chain acids (34.0%). Iso-branching was found in both even- and odd-numbered
      acids, but anteiso-branching was found mostly in odd-numbered acids. The presence
      of propionic acid at the 3 position of the glycerol moiety in male ADG, and of
      isovaleric and 2-methylbutyric acids at the same position in female ADG was
      demonstrated by NMR spectrometry. Alkyl portions also exhibited sexual dimorphism
      in these lipids. ADG from males consisted of straight aliphatic chains, but
      branched chain components occupied almost half (45%) in ADG from females, and the
      branching resided at the iso- and anteiso-positions. The ADGs in glands from the
      two sexes were separated by Iatrobeads column chromatography into three and two
      subfractions, respectively. The fatty acid and alkyl compositions of these
      subfractions coincided with the above-mentioned results and with the behavior of
      the ADGs on thin-layer plates. These findings suggest that a sex hormone affects
      the metabolism of valine, leucine and isoleucine, and sexual dimorphism of ADGs
      occurs in the Harderian gland.

PMID- 7629039
TI  - Hepatocyte growth factor promotes the growth of cytotrophoblasts by the paracrine
      mechanism.
AB  - Both placental and decidual tissues contained extractable HGF, the former HGF
      level (31.4 +/- 23.4 ng/mg total protein) being approximately 30 times the latter
      HGF level. When the localization of HGF protein and HGF mRNA in placental tissues
      was examined by immunohistological staining and in situ hybridization, HGF
      protein and HGF mRNA were detected in the mesenchymal cells of the placenta, but
      were absent in the cytotrophoblast and syncytiotrophoblast. Although c-met
      protein was expressed in the cytotrophoblast, this receptor was not detectable in
      the syncytiotrophoblast by immunohistochemical methods. c-met mRNA was detected
      in placental cell line (tPA30-1) and 4 choriocarcinoma cell lines (BeWo, Jar, Jeg
      3, and NUC-1), but HGF mRNA was absent in these cells. When cytotrophoblast cells
      were cultured in a serum-free medium in the presence of HGF, their DNA synthesis
      was enhanced depending on the HGF concentration, although human placental
      lactogen secretion itself was not affected by HGF. These results demonstrated
      that HGF promotes the growth of the cytotrophoblast by the paracrine mechanism,
      although it does not serve as a placental differentiation factor.

PMID- 7629040
TI  - Photoaffinity labeling of influenza virus RNA polymerase PB1 subunit with 8-azido
      GTP.
AB  - 8-Azido GTP (8-N3 GTP) was demonstrated to be polymerized into RNA by influenza
      virus-associated RNA polymerase at about one tenth the rate of GTP incorporation.
      The Km value for the azido analogue of GTP in primer-dependent RNA synthesis was
      94 microM whereas Km for the natural substrate, GTP, was 6.7 microM. Upon
      exposure of a mixture of 8-N3 [alpha-32P]GTP and influenza virus
      ribonucleoprotein (RNP) complexes to ultraviolet light, the PB1 subunit of viral
      RNA polymerase was selectively radio-labeled. The photo-labeling of PB1 was
      competed strongly by GTP and to lesser extents by other nucleoside 5'
      triphosphates. These results altogether support the prediction that the substrate
      binding site (S site) of influenza RNA polymerase is located on the PB1 protein.
      In the presence of ApG primer, the 8-N3 GTP binding was reduced to about 40%
      level, suggesting that the GTP analogue can bind not only to the S site but also
      to the primer- and product-binding site (P site).

PMID- 7629041
TI  - Proton/electron stoichiometry of mitochondrial bc1 complex. Influence of pH and
      transmembrane delta pH.
AB  - The effect of pH and transmembrane delta pH on the efficiency of the proton pump
      of the mitochondrial bc1 complex both in situ and in the reconstituted state was
      studied. In both cases the H+/e- ratio for vectorial proton translocation by the
      bc1 complex respiring at the steady state, under conditions in which the
      transmembrane pH difference (delta pH) represents the only component of the
      proton motive force (delta p), was significantly lower than that measured under
      level flow conditions. The latter amounts, at neutral pH, to 1 (2 including the
      scalar H+ release). In the reconstituted system steady-state delta pH was
      modulated by changing the intravesicular buffer as well as the intra/extra
      liposomal pH. Under these conditions the H+/e- ratio varied inversely with the
      delta pH. The data presented show that delta pH exerts a critical control on the
      proton pump of the bc1 complex. Increasing the external pH above neutrality
      caused a decrease of the level flow H+/e- ratio. This effect is explained in
      terms of proton/electron linkage in b cytochromes.

PMID- 7629042
TI  - The native F0F1-inhibitor protein complex from beef heart mitochondria and its
      reconstitution in liposomes.
AB  - A functional F0F1 ATP synthase that contains the endogenous inhibitor protein
      (F0F1I) was isolated by the use of two combined techniques [Adolfsen, R.,
      McClung, J.A., and Moudrianakis, E. N. (1975). Biochemistry 14, 1727-1735;
      Dreyfus, G., Celis, H., and Ramirez, J. (1984). Anal. Biochem. 142, 215-220]. The
      preparation is composed of 18 subunits as judged by SDS-PAGE. A steady-state
      kinetic analysis of the latent ATP synthase complex at various concentrations of
      ATP showed a Vmax of 1.28 mumol min-1 mg-1, whereas the Vmax of the complex
      without the inhibitor was 8.3 mumol min-1 mg-1. In contrast, the Km for Mg-ATP of
      F0F1I was 148 microM, comparable to the Km value of 142 microM of the F0F1
      complex devoid of IF1. The hydrolytic activity of the F0F1I increased severalfold
      by incubation at 60 degrees C at pH 6.8, reaching a maximal ATPase activity of
      9.5 mumol min-1 mg-1; at pH 9.0 a rapid increase in the specific activity of
      hydrolysis was followed by a sharp drop in activity. The latent ATP synthase was
      reconstituted into liposomes by means of a column filtration method. The
      proteoliposomes showed ATP-Pi exchange activity which responded to phosphate
      concentration and was sensitive to energy transfer inhibitors like oligomycin and
      the uncoupler p-trifluoromethoxyphenylhydrazone.

PMID- 7629043
TI  - Content and binding characteristics of the mitochondrial ATPase inhibitor, IF1,
      in the tissues of several slow and fast heart-rate homeothermic species and in
      two poikilotherms.
AB  - We determined the IF1 contents of pig, rabbit, rat, mouse, guinea pig, pigeon,
      turtle, and frog heart mitochondria and the effects of varying ionic strength
      upon the IF1-mediated inhibition of the ATPase activity of IF1-depleted rabbit
      heart mitochondrial particles (RHMP) by IF1-containing extracts from these same
      eight species. The IF1 binding experiments were run at both species-endogenous
      IF1 levels and at an IF1 level normalized to that present in rabbit heart
      mitochondria. When species-endogenous levels of rabbit heart IF1 or either
      species-endogenous or normalized levels of pig heart IF1 were incubated with RHMP
      over a range of KCl concentrations, increasing the [KCl] to 150 mM had relatively
      little effect on IF1-mediated ATPase inhibition. When either species-endogenous
      or normalized levels of guinea pig, pigeon, turtle, or frog heart IF1 were
      incubated with RHMP under the same conditions, increasing [KCl] to 150 mM nearly
      completely blocked IF1-mediated ATPase inhibition. While species-endogenous
      levels of rat and mouse heart IF1 inhibited the ATPase activity of RHMP virtually
      not at all at any [KCl] examined, normalized levels of rat and mouse IF1
      inhibited the ATPase activity of RHMP to the same extents as species-endogenous
      levels of pig and rabbit heart IF1, respectively, in the presence of increasing
      [KCl]. These experiments suggest that, while pig and rabbit heart mitochondria
      contain a full complement of higher-affinity IF1, pigeon, guinea pig, turtle, and
      frog heart mitochondria cell contain essentially a full complement of a lower
      affinity form of IF1.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7629044
TI  - Inhibition by trifluoperazine of ATP synthesis and hydrolysis by particulate and
      soluble mitochondrial F1: competition with H2PO4-.
AB  - The effect of trifluoperazine (TFP) on the ATPase activity of soluble and
      particulate F1-ATPase and on ATP synthesis driven by succinate oxidation in
      submitochondrial particles from bovine heart was studied at pH 7.4 and 8.8. At
      the two pH, TFP inhibited ATP hydrolysis. Inorganic phosphate protected against
      the inhibiting action of TFP. The results on the effect of various concentrations
      of phosphate in the reversal of the action of TFP on hydrolysis at pH 7.4 and 8.8
      showed that H2PO4- is the species that competes with TFP. The effect of TFP on
      oxidative phosphorylation was studied at concentrations that do not produce
      uncoupling or affect the aerobic oxidation of succinate (< 15 microM). TFP
      inhibited oxidative phosphorylation to a higher extent at pH 8.8 than at pH 7.4;
      this was through a diminution in the Vmax, and an increase in the Km for
      phosphate. Data on phosphate uptake during oxidative phosphorylation at several
      pH showed that H2PO4- is the true substrate for oxidative phosphorylation. Thus,
      in both synthesis and hydrolysis of ATP, TFP and H2PO4- interact with a common
      site. However, there is a difference in the sensitivity to TFP of ATP synthesis
      and hydrolysis; this is more noticeable at pH 8.8, i.e., ATPase activity of
      soluble F1 remains at about 40% of the activity of the control in a concentration
      range of TFP of 40-100 microM, whereas in oxidative phosphorylation 14 microM TFP
      produces a 60% inhibition of phosphate uptake.

PMID- 7629045
TI  - Differential response of the NADH oxidase of plasma membranes of rat liver and
      hepatoma and HeLa cells to thiol reagents.
AB  - NADH oxidase activity of plasma membranes from rat hepatoma and HeLa cells
      responded to thiol reagents in a manner different from that of plasma membranes
      of liver. Specifically, the NADH oxidase activity of plasma membranes of HeLa
      cells was inhibited by submicromolar concentrations of the thiol reagents p
      chloromercuribenzoate (PCMB), N-ethylmaleimide (NEM), or 5,5'-dithiobis-(2
      nitrophenylbenzoic acid) (DTNB), whereas that of the rat liver plasma membranes
      was unaffected or stimulated over a wide range of concentrations extending into
      the millimolar range. With some hepatoma preparations, the NADH oxidase activity
      of hepatoma plasma membranes was stimulated rather than inhibited by PCMB,
      whereas with all preparations of hepatoma plasma membranes, NEM and DTNB
      stimulated the activity. In contrast, NADH oxidase activity of rat liver plasma
      membrane was largely unaffected over the same range of PCMB concentrations that
      either stimulated or inhibited with rat hepatoma or HeLa cell plasma membranes.
      Dithiothreitol and glutathione stimulated NADH oxidase activity of plasma
      membranes of rat liver and hepatoma but inhibited that of HeLa plasma membranes.
      The findings demonstrate a difference between the NADH oxidase activity of normal
      rat liver plasma membranes of rat hepatoma and HeLa cell plasma membranes in
      addition to the differential response to growth factors and hormones reported
      previously (Bruno et al., 1992). Results are consistent with a structural
      modification of a NADH oxidase activity involving thiol groups present in plasma
      membranes of rat hepatoma and HeLa cells but absent or inaccessible with plasma
      membranes of rat liver.

PMID- 7629046
TI  - Characterization and functional reconstitution of the multidrug transporter.
AB  - P-Glycoprotein, the multidrug transporter, is isolated from the plasma membrane
      of CHRC5 cells using a selective two-step detergent extraction procedure. The
      partially purified protein displays a high level of ATPase activity, which has a
      high KM for ATP, is stimulated by drugs, and can be distinguished from that of
      other membrane ATPases by its unique inhibition profile. Delipidation completely
      inactivates ATPase activity, which is restored by the addition of fluid lipid
      mixtures. P-Glycoprotein was reconstituted into lipid bilayers with retention of
      both drug transport and ATPase activity. Proteoliposomes containing P
      glycoprotein display osmotically sensitive ATP-dependent accumulation of 3H
      colchicine in the vesicle lumen. Drug transport is active, generating a stable
      5.6-fold concentration gradient, and can be blocked by compounds in the multidrug
      resistance spectrum. Reconstituted P-glycoprotein also exhibits a high level of
      ATPase activity which is further stimulated by various drugs. P-Glycoprotein
      therefore functions as an active drug transporter with constitutive ATPase
      activity.

PMID- 7629048
TI  - Multidrug resistance--a fascinating, clinically relevant problem in
      bioenergetics.

PMID- 7629047
TI  - Purification and reconstitution of functional human P-glycoprotein.
AB  - The overexpression of the P-glycoprotein, the MDR1 gene product, has been linked
      to the development of resistance to multiple cytotoxic natural product anticancer
      drugs in certain cancers and cell lines derived from tumors. P-glycoprotein, a
      member of the ATP-binding cassette (ABC) superfamily of transporters, is believed
      to function as an ATP-dependent drug efflux pump with broad specificity for
      chemically unrelated hydrophobic compounds. We review here recent studies on the
      purification and reconstitution of P-glycoprotein to elucidate the mechanism of
      drug transport. P-glycoprotein from the human carcinoma multidrug resistant cell
      line, KB-V1, was purified by sequential chromatography on anion exchange followed
      by a lectin (wheat germ agglutinin) column. Proteoliposomes reconstituted with
      pure protein exhibited high levels of drug-stimulated ATPase activity as well as
      ATP-dependent [3H]vinblastine accumulation. Both the ATPase and vinblastine
      transport activities of the reconstituted P-glycoprotein were inhibited by
      vanadate. In addition, the vinblastine transport was inhibited by verapamil and
      daunorubicin. These studies provide strong evidence that the human P-glycoprotein
      functions as an ATP-dependent drug transporter. The development of the
      reconstitution system and the availability of recombinant protein in large
      amounts due to recent advances in overexpression of P-glycoprotein in a
      heterologous expression system should facilitate a better understanding of the
      function of this novel protein.

PMID- 7629049
TI  - ATP hydrolysis by multidrug-resistance protein from Chinese hamster ovary cells.
AB  - ATPase activity of multidrug-resistance protein (P-glycoprotein, Pgp) from
      Chinese hamster ovary cells was studied. Catalytic characteristics were
      established for Pgp both in its natural plasma membrane environment and in
      purified reconstituted protein. Generally the two preparations of Pgp behaved
      similarly, and demonstrated low affinity for MgATP, low nucleotide specificity,
      preference for Mg-nucleotide, and pH optimum near 7.5. A high-affinity binding
      site involved in catalysis was not apparent. Effective covalent inactivators were
      NBD-C1, NEM, 8-azido-ATP, and 2-azido-ATP. DCCD, FITC, and pyridoxal phosphate
      were only weakly inhibitory. Lipid composition was found to affect the degree of
      drug stimulation of ATPase in purified reconstituted Pgp, suggesting that the
      lipid environment affects coupling between drug-binding and catalytic sites, and
      that Pgp expressed in different tissues could show different functional
      characteristics.

PMID- 7629050
TI  - Drug-stimulated ATPase activity of the human P-glycoprotein.
AB  - The human multidrug resistance protein, or P-glycoprotein (Pgp), exhibits a high
      capacity drug-dependent ATP hydrolytic activity that is a direct reflection of
      its drug transport capability. This activity is readily measured in membranes
      isolated from cultured insect cells infected with a baculovirus carrying the
      human mdr1 cDNA. The drug-stimulated ATPase activity is a useful alternative to
      conventional screening systems for identifying high-affinity drug substrates of
      the Pgp with potential clinical value as chemosensitizers for tumor cells that
      have become drug resistant. Using this assay system, a variety of drugs have been
      directly shown to interact with the Pgp. Many of the drugs stimulate the Pgp
      ATPase activity, but certain drugs bind tightly to the drug-binding site of the
      Pgp without eliciting ATP hydrolysis. Either class of drugs may be useful as
      chemosensitizing agents. The baculovirus/insect cell Pgp ATPase assay system may
      also facilitate future studies of the molecular structure and mechanism of the
      Pgp.

PMID- 7629051
TI  - Heterologous expression systems for P-glycoprotein: E. coli, yeast, and
      baculovirus.
AB  - Chemotherapy, though it remains one of the front-line weapons used to treat human
      cancer, is often ineffective due to drug resistance mechanisms manifest in tumor
      cells. One common pattern of drug resistance, characterized by simultaneous
      resistance to multiple amphipathic, but otherwise structurally dissimilar
      anticancer drugs, is termed multidrug resistance. Multidrug resistance in various
      model systems, covering the phylogenetic range from bacteria to man, can be
      conferred by mammalian P-glycoproteins (PGPs), often termed multidrug
      transporters. PGPs are 170-kD polytopic membrane proteins, predicted to consist
      of two homologous halves, each with six membrane spanning regions and one ATP
      binding site. They are members of the ATP-binding cassette (ABC) superfamily of
      transporters, and are known to function biochemically as energy-dependent drug
      efflux pumps. However, much remains to be learned about PGP structure-function
      relationships, membrane topology, posttranslational regulation, and bioenergetics
      of drug transport. Much of the recent progress in the study of the human and
      mouse PGPs has come from heterologous expression systems which offer the benefits
      of ease of genetic selection and manipulation, and/or short generation times of
      the organism in which PGPs are expressed, and/or high-level expression of
      recombinant PGP. Here we review recent studies of PGP in E. coli, baculovirus,
      and yeast systems and evaluate their utility for the study of PGPs, as well as
      other higher eukaryotic membrane proteins.

PMID- 7629052
TI  - Effects of phosphorylation of P-glycoprotein on multidrug resistance.
AB  - Cells expressing elevated levels of the membrane phosphoprotein P-glycoprotein
      exhibit a multidrug resistance phenotype. Studies involving protein kinase
      activators and inhibitors have implied that covalent modification of P
      glycoprotein by phosphorylation may modulate its biological activity as a
      multidrug transporter. Most of these reagents, however, have additional
      mechanisms of action and may alter drug accumulation within multidrug resistant
      cells independent of, or in addition to, their effects on the state of
      phosphorylation of P-glycoprotein. The protein kinase(s) responsible for P
      glycoprotein phosphorylation has(ve) not been unambiguously identified, although
      several possible candidates have been suggested. Recent biochemical analyses
      demonstrate that the major sites of phosphorylation are clustered within the
      linker region that connects the two homologous halves of P-glycoprotein.
      Mutational analyses have been initiated to confirm this finding. Preliminary data
      obtained from phosphorylation- and dephosphorylation-defective mutants suggest
      that phosphorylation of P-glycoprotein is not essential to confer multidrug
      resistance.

PMID- 7629053
TI  - Using purified P-glycoprotein to understand multidrug resistance.
AB  - Since P-glycoprotein was discovered almost 20 years ago, its causative role in
      multidrug resistance has been established, but central problems of its
      biochemistry have not been definitively resolved. Recently, major advances have
      been made in P-glycoprotein biochemistry with the use of purified and
      reconstituted P-glycoprotein, as well as membranes from nonmammalian cells
      containing heterologously expressed P-glycoprotein. In this review we describe
      recent findings using these systems which are elucidating the molecular mechanism
      of P-glycoprotein-mediated drug transport.

PMID- 7629054
TI  - Yeast multidrug resistance: the PDR network.
AB  - This minireview describes a network of genes involved in multiple drug resistance
      of the yeast S. cerevisiae. The transcription regulators, PDR1, PDR3, PDR7, and
      PDR9 control the expression of the gene PDR5, encoding a membrane protein of the
      ATP-binding-cassette superfamily and functioning as a drug extrusion pump. Next
      to PDR5, several other target genes, encoding membrane pumps of the ABC type,
      such as SNQ2, STE6, PDR10, PDR11, YOR1, but also other membrane-associated (such
      as GAS1, D4405) or soluble proteins (such as G3PD), involved or not in multidrug
      resistance, are found to be controlled by PDR1. On another side, the PDR3
      regulator participates with its homolog PDR1 to co- and auto-regulation circuits
      of yeast multidrug resistance.

PMID- 7629056
TI  - Mechanisms of metalloregulation of an anion-translocating ATPase.
AB  - The ars (arsenical resistance) operon cloned from R-factor R773 has five genes
      that encode two repressor proteins, ArsR and ArsD, and three structural proteins,
      ArsA, ArsB, and ArsC. The ArsA and ArsB proteins form a membrane-bound pump that
      functions as an oxyanion-translocating ATPase. The substrates of the pump are the
      oxyanions arsenite or antimonite. The ArsC protein is an arsenate reductase that
      reduces arsenate to arsenite, which is subsequently pumped out of the cell. This
      review deals with the mechanism of transcriptional regulation by the ArsR
      repressor and allosteric regulation of the ArsA protein, the catalytic subunit of
      the pump. The chemical nature of the inducer plays an important role in
      regulation. In solution arsenite or antimonite exist as oxyanions and reacts with
      the cysteines in proteins. In both transcriptional regulation by the ArsR
      repressor and allosteric regulation of the ArsA ATPase, the ability of As(III)
      and Sb(III) to interact with the cysteines of the proteins, involves their action
      as effector.

PMID- 7629055
TI  - Multidrug resistance and P-glycoproteins in parasitic protozoa.
AB  - Drug resistance has emerged as a devasting impediment to the treatment and
      control of diseases of parasitic origin. The underlying mechanisms that
      contribute to this drug resistance in field isolates, however, are poorly
      understood. Members of the P-glycoprotein gene (pgp) family have been identified,
      cloned, and sequenced in Plasmodia, Leishmania, and Entamoeba, and variations in
      pgp copy number and/or expression have been implicated as a basis for drug
      resistance in each of these genera. The spectrum of drugs to which parasitic
      protozoa containing amplified pgp genes and/or transcripts are refractory range
      from a phenotype similar to that observed with multidrug-resistant mammalian
      cells to those that are completely distinct. The availability of molecular probes
      to pgp genes provides valuable reagents to dissect the role of pgp gene
      amplification and overexpression in mediating drug resistance in parasitic
      protozoa and to determine the physiological function of P-glycoproteins in this
      clinically consequential group of human pathogens.

PMID- 7629057
TI  - Low affinity binding of interleukin-1 beta and intracellular signaling via NF
      kappa B identify Fit-1 as a distant member of the interleukin-1 receptor family.
AB  - The fit-1 gene gives rise to two different mRNA isoforms, which code for soluble
      (Fit-1S) and membrane-bound (Fit-1M) proteins related to the type I interleukin
      (IL)-1 receptor. To investigate IL-1 binding, we have synthesized and purified
      histidine-tagged polypeptides corresponding to Fit-1S and the extracellular
      domain of the type I IL-1 receptor using a vaccinia expression system. Fit-1S is
      shown to interact with IL-1 beta, but not with IL-1 alpha. However, Fit-1S binds
      IL-1 beta only with low affinity in contrast to the IL-1 receptor, suggesting
      that IL-1 beta is not a physiological ligand of Fit-1S. Moreover, expression of
      the membrane-bound protein Fit-1M in transiently transfected Jurkat cells did not
      result in activation of the transcription factor NF-kappa B following IL-1 beta
      treatment. However, a chimeric protein consisting of the extracellular domain of
      the type I IL-1 receptor and of the transmembrane and intracellular regions of
      Fit-1M stimulated NF-kappa B-dependent transcription as efficiently as the full
      length type I IL-1 receptor. These data indicate that Fit-1M is a signaling
      molecule belonging to the IL-1 receptor family.

PMID- 7629058
TI  - The translation product of the presumptive Thermococcus celer TATA-binding
      protein sequence is a transcription factor related in structure and function to
      Methanococcus transcription factor B.
AB  - A gene for a putative homolog of TATA-binding protein (TBP) from Thermococcus
      celer has been expressed in Escherichia coli, and the function of the purified
      recombinant protein was studied in a Methanococcus-derived cell-free
      transcription system. Thermococcus TBP can replace archaeal transcription factor
      B (aTFB) in cell-free transcription reactions. This transcriptional activation is
      TATA box-dependent and occurs both on tRNA(Val) and protein-encoding genes as
      templates indicating that Thermococcus TBP is a general transcription factor.
      Antibodies raised against Thermococcus TBP bind to Methanococcus aTFB and inhibit
      a TFB activity. These findings demonstrate that Thermococcus TBP (like eucaryal
      TBPs) can direct specific transcription from TATA boxes.

PMID- 7629059
TI  - MacMARCKS mutation blocks macrophage phagocytosis of zymosan.
AB  - A major protein kinase C substrate, MacMARCKS (F52, MPR), was examined for its
      role in phagocytosis. In macrophage-phagocytosing zymosan particles, MacMARCKS
      was concentrated around nascent phagosomes as detected by immunofluorescent
      microscopy. The effector domain of MacMARCKS contains the phosphorylation sites,
      a calmodulin binding site, as well as a putative actin binding site. Stable J774
      macrophage cell lines constitutively expressing effector domain deletion mutants
      of MacMARCKS were generated. When given zymosan particles, these transfectants
      showed approximately a 90% reduction in their phagocytic capacity. The receptor
      mediated endocytosis of acetylated low density lipoproteins, however, was not
      affected by the mutant. These results strongly suggest the involvement of
      MacMARCKS in macrophage phagocytosis.

PMID- 7629060
TI  - Rho family GTPases bind to phosphoinositide kinases.
AB  - Rho family GTPases appear to play an important role in the regulation of the
      actin cytoskeleton, but the mechanism of regulation is unknown. Since
      phosphoinositide 3-kinase and phosphatidylinositol 4,5-bisphosphate have also
      been implicated in actin reorganization, we investigated the possibility that Rho
      family members interact with phosphoinositide kinases. We found that both GTP-
      and GDP-bound Rac1 associate with phosphatidylinositol-4-phosphate 5-kinase in
      vitro and in vivo. Phosphoinositide 3-kinase also bound to Rac1 and Cdc42Hs, and
      these interactions were GTP-dependent. Stimulation of Swiss 3T3 cells with
      platelet-derived growth factor induced the association of PI 3-kinase with Rac in
      immunoprecipitates. PI 3-kinase activity was also detected in Cdc42
      immunoprecipitates from COS7 cells. These results suggest that phosphoinositide
      kinases are involved in Rho family signal transduction pathways and raise the
      possibility that the effects of Rho family members on the actin cytoskeleton are
      mediated in part by phosphoinositide kinases.

PMID- 7629061
TI  - Lethality in yeast of trichothiodystrophy (TTD) mutations in the human xeroderma
      pigmentosum group D gene. Implications for transcriptional defect in TTD.
AB  - Mutations in the human XPD gene result in a defect in nucleotide excision repair
      of ultraviolet damaged DNA and cause the cancer-prone syndrome xeroderma
      pigmentosum (XP). Besides XP, mutations in XPD can cause another seemingly
      unrelated syndrome, trichothiodystrophy (TTD), characterized by sulfur-deficient
      brittle hair, ichthyosis, and physical and mental retardation. To ascertain the
      underlying defect responsible for TTD, we have expressed the TTD mutant proteins
      in the yeast Saccharomyces cerevisiae and determined if these mutations can
      rescue the inviability of a rad3 null mutation. RAD3, the S. cerevisiae
      counterpart of XPD, is required for nucleotide excision repair and also has an
      essential role in RNA polymerase II transcription. Expression of the wild type
      XPD protein or the XPD Arg-48 protein carrying a mutation in the DNA helicase
      domain restores viability to the rad3 null mutation. Interestingly, the XPD
      variants containing TTD mutations fail to complement the lethality of the rad3
      null mutation, strongly suggesting that TTD mutations impair the ability of XPD
      protein to function normally in RNA polymerase II transcription. From our
      studies, we conclude that XPD DNA helicase activity is not essential for
      transcription and infer that TTD mutations in XPD result in a defect in
      transcription.

PMID- 7629062
TI  - A SecY homolog in Arabidopsis thaliana. Sequence of a full-length cDNA clone and
      import of the precursor protein into chloroplasts.
AB  - Proteins are translocated across the thylakoid membrane by two distinct pathways
      in higher plant chloroplasts, one of which is related to prokaryotic Sec
      dependent translocation mechanisms. SecY is an essential, hydrophobic component
      of the membrane-bound translocase complex in bacteria, and we report here the
      nucleotide sequence of a full-length cDNA encoding a homolog of SecY from
      Arabidopsis thaliana. The predicted protein of 551 residues includes an amino
      terminal extension of approximately 120 residues when compared with other SecY
      proteins. The deduced sequence of the mature protein, cpSecY, is 41% identical
      with SecY from Synechococcus and 33% identical with the Escherichia coli protein.
      The extension serves to target the protein into chloroplasts; transcription
      translation of the cDNA yields a 58-kDa precursor protein which is imported into
      pea chloroplasts, processed to a product of 46 kDa, and targeted into the
      thylakoid membrane.

PMID- 7629063
TI  - Constitutive ion fluxes and substrate binding domains of human glutamate
      transporters.
AB  - Application of L-glutamate activates ionic currents in voltage-clamped Xenopus
      oocytes expressing cloned human excitatory amino acid transporters (EAATs).
      However, even in the absence of L-glutamate, the membrane conductance of oocytes
      expressing EAAT1 was significantly increased relative to oocytes expressing EAAT2
      or control oocytes. Whereas transport mediated by EAAT2 is blocked by the non
      transported competitive glutamate analog kainate (Ki = 14 microM), EAAT1 is
      relatively insensitive (Ki > 3 mM). Substitution of a block of 76 residues from
      EAAT2 into EAAT1, in which 18 residues varied from EAAT1, conferred high affinity
      kainate binding to EAAT1, and application of kainate to oocytes expressing the
      chimeric transporter blocked a pre-existing monovalent cation conductance that
      displayed a permeability sequence K+ > Na+ > Li+ >> choline+. The results
      identify a structural domain of glutamate transporters that influences kainate
      binding and demonstrate the presence of a constitutive ion-selective pore in the
      transporter.

PMID- 7629064
TI  - Proofreading in vivo. Editing of homocysteine by aminoacyl-tRNA synthetases in
      Escherichia coli.
AB  - Editing reactions are an essential part of biological information transfer
      processes that require high accuracy, such as replication, transcription, and
      translation. The editing in amino acid selection for protein synthesis by an
      aminoacyl-tRNA synthetase, the first proofreading process discovered in the flow
      of genetic information, prevents attachment of incorrect amino acids to tRNA. Of
      numerous editing reactions studied in vitro, only one, editing of homocysteine by
      methionyl-tRNA synthetase, has also been demonstrated in vivo. It is therefore
      unclear to what extent editing of errors is physiologically relevant. Here we
      show that isoleucyl- and leucyl-tRNA synthetases also edit homocysteine by
      cyclizing it to homocysteine thiolactone in the bacterium Escherichia coli. These
      and other data also suggest that metabolite compartmentation or channeling
      governs which synthetase participates in editing in bacterial cells.

PMID- 7629065
TI  - Molecular cloning of Ebnerin, a von Ebner's gland protein associated with taste
      buds.
AB  - Salivary secretions modulate taste perception. Taste buds in the circumvallate
      and foliate papillae are bathed in secretions of unique lingual salivary glands,
      von Ebner's glands (VEG). We have identified a rat cDNA encoding a novel protein
      of 1290 amino acids, Ebnerin, that is specifically expressed in VEG and released
      onto the tongue surface along the apical region of taste buds in the clefts of
      circumvallate papillae. Ebnerin possesses a putative single transmembrane domain
      at the C terminus with 17 amino acids in the cytoplasmic area. The extracellular
      region of Ebnerin contains a number of repeated domains with homology to the
      scavenger receptor cysteine-rich domain and to a repeated domain of bone
      morphogenetic protein-I and other related proteins. Western blot analysis reveals
      that Ebnerin exists in particulate and soluble forms in VEG and is present in
      secretions from VEG. In situ hybridization and immunohistochemistry demonstrate
      that Ebnerin is located in secretory duct epithelial cells of VEG and is released
      onto the tongue surface along the apical region of taste buds in the clefts of
      circumvallate papillae. The unique structure and localization of Ebnerin suggest
      that it may function as a binding protein in saliva for the regulation of taste
      sensation.

PMID- 7629066
TI  - Ribosomal decoding processes at codons in the A or P sites depend differently on
      2'-OH groups.
AB  - The importance of 2'-OH groups of codons for binding of cognate tRNAs to
      ribosomal P and A sites was analyzed applying the following strategy. An mRNA of
      41 nucleotides was synthesized with the structure C16-GAA-UUC-GUC-C16 coding for
      glutamic acid (E), phenylalanine (F) and valine (V), respectively, in the middle
      (EFV-mRNA). A second template, the E(dF)V-mRNA, was identical except that it
      carried a deoxyribo-codon-dUdUdC- for phenylalanine. tRNA binding to the P site
      is totally insensitive to the presence or absence of the 2'-OH group of the P
      site codon, and tRNA binding to the P site is also not affected if the A-site
      codon lacks the 2'-OH groups. However, binding is impaired if the deoxy-codon is
      present at the E site. In sharp contrast, the A-site binding of Ac-aminoacyl-tRNA
      was severely reduced in the presence of the deoxy-codon at the A site as well as
      at the P site. The results demonstrate that the correctness of base pairing is
      also "sensed" via a correct sugar structure of the codon, e.g. positioning of the
      sugar pucker (2'-OH), during the decoding process at the A site (elongation) but
      not during the decoding at the P site (initiation).

PMID- 7629067
TI  - Fourier transform infrared spectroscopy study of the secondary structure of the
      reconstituted Neurospora crassa plasma membrane H(+)-ATPase and of its membrane
      associated proteolytic peptides.
AB  - We reconstituted purified plasma membrane H(+)-ATPase from Neurospora crassa into
      soybean phospholipid vesicles (lipid/ATPase ratio of 5:1 w/w). The
      proteoliposomes contained an active ATPase, oriented inside-out. They were
      subjected to proteolysis by using Pronase, proteinase K, trypsin, and
      carboxypeptidase Y. Fourier transform infrared attenuated total reflection
      spectroscopy indicates that the amount of protein remaining after hydrolysis and
      elimination of the extramembrane domain of ATPase represents about 43% of the
      intact protein. The secondary structure of intact ATPase and of the membrane
      associated domain of ATPase was determined by infrared spectroscopy. The membrane
      domain shows a typical alpha-helix and beta-sheet absorption. Polarized infrared
      spectroscopy reveals that the orientation of the helices is about perpendicular
      to the membrane. Amide hydrogen/deuterium exchange kinetics performed for the
      intact H(+)-ATPase and for the membrane-associated domain demonstrate that this
      part of ATPase shows less accessibility to the solvent than the entire protein
      but remains much more accessible to the solvent than bacteriorhodopsin membrane
      segments.

PMID- 7629069
TI  - Tryptophan-containing alpha-subunits of the Escherichia coli tryptophan synthase.
      Enzymatic and urea stability properties.
AB  - Early studies suggested that the Escherichia coli tryptophan synthase alpha
      subunit unfolded in a two-step process in which there was a stable intermediate
      composed of a native alpha-1 folding unit (residues 1-188) and a completely
      unfolded alpha-2 folding unit (residues 189-268). More recent evidence has
      indicated that such a structure for the intermediate seems unlikely. In this
      report, single Trp residues (absent in the wild-type alpha-subunit) are
      substituted separately for Phe residues at positions 139 (in alpha-1) and 258 (in
      alpha-2) to produce the F139W, F258W, and F139W/F258W mutant alpha-subunits. The
      UV absorbance and fluorescence properties of the F139W/F258W double mutant are
      identical with those of equimolar mixtures of the single mutants, suggesting that
      the Trp residue at each position can independently report the behavior of its
      respective folding unit. Each mutant alpha-subunit is wild-type enzymatically,
      and when UV absorbance is monitored, the urea-induced unfolding of the three
      tryptophan-containing alpha-subunits is virtually identical to the wild-type
      protein. These wild-type properties make these proteins attractive candidates for
      a fluorescence examination of the behavior of the individual folding units and
      the structure of potential intermediate(s) and as host proteins for the insertion
      of our existing destabilizing and/or stabilizing mutational alterations.

PMID- 7629068
TI  - Amino terminus and the first four membrane-spanning segments of the Arabidopsis
      K+ channel KAT1 confer inward-rectification property of plant-animal chimeric
      channels.
AB  - The Arabidopsis hyperpolarization-activated (inward-rectifying) K+ channel KAT1
      is structurally more similar to animal depolarization-activated (outward
      rectifying) K+ channels than to animal hyperpolarization-activated K+ channels.
      To gain insight into the structural basis for the opposite voltage dependences of
      plant inward-rectifying and animal outward-rectifying K+ channels, we constructed
      recombinant chimeric channels between the hyperpolarization-activated K+ channel
      KAT1 and a Xenopus depolarization-activated K+ channel. We report here that two
      of the chimeric constructs, which contain the first third of the KAT1 sequence,
      including the first four membrane-spanning segments (S1-S4) and the linker
      sequence between the fourth and fifth membrane-spanning segments, express
      functional channels that retain activation by hyperpolarization, but not
      depolarization. These two chimeric channels are no longer selective for K+. The
      chimeras are selective for cations over anions and are permeable to Ca2+.
      Therefore, unlike animal hyperpolarization-activated K+ channels, in which the
      carboxyl terminus is important for inward rectification induced by Mg2+ and
      polyamine block, the plant KAT1 channel has its major determinants for inward
      rectification in the amino-terminal region, which ends at the end of the S4-S5
      linker.

PMID- 7629070
TI  - Identification of the major SHPTP2-binding protein that is tyrosine
      phosphorylated in response to insulin.
AB  - Immunoprecipitation of the cytosolic Src homology 2 domain-containing protein
      tyrosine phosphatase, SHPTP2, from insulin-stimulated 3T3L1 adipocytes or Chinese
      hamster ovary cells expressing the human insulin receptor resulted in the
      coimmunoprecipitation of a diffuse tyrosine-phosphorylated band in the 115-kDa
      protein region on SDS-polyacrylamide gels. Although platelet-derived growth
      factor induced the tyrosine phosphorylation of the platelet-derived growth factor
      receptor and SHPTP2, there was no significant increase in the
      coimmunoprecipitation of tyrosine-phosphorylated pp115 with SHPTP2. SHPTP2 was
      also associated with tyrosine-phosphorylated insulin receptor substrate-1, but
      this only accounted for < 2% of the total immunoreactive SHPTP2 protein.
      Similarly, only a small fraction of the total amount of tyrosine-phosphorylated
      insulin receptor substrate-1 (< 4%) was associated with SHPTP2. Expression and
      immunoprecipitation of a Myc epitope-tagged wild-type SHPTP2 (Myc-WT-SHPTP2) and
      a catalytically inactive point mutant of SHPTP2 (Myc-C/S-SHPTP2) also
      demonstrated an insulin-dependent association of SHPTP2 with tyrosine
      phosphorylated pp115. Furthermore, expression of the catalytically inactive
      SHPTP2 mutant resulted in a marked enhancement in the amount of
      coimmunoprecipitated tyrosine-phosphorylated pp115 compared with the expression
      of wild-type SHPTP2. These data indicate that the insulin-stimulated tyrosine
      phosphorylated 115-kDa protein is the predominant in vivo SHPTP2-binding protein
      and that pp115 may function as a physiological substrate for the SHPTP2 protein
      tyrosine phosphatase.

PMID- 7629071
TI  - Enhanced transglycosylation activity of Arthrobacter protophormiae endo-beta-N
      acetylglucosaminidase in media containing organic solvents.
AB  - The transglycosylation activity of endo-beta-N-acetylglucosaminidase from
      Arthrobacter protophormiae (endo-A) was enhanced by inclusion of organic solvents
      in the reaction mixture. In aqueous solution, the transglycosylation yield
      relative to starting substrate was 32% using Man9GlcNAc2Asn as donor and 0.5 M
      GlcNAc as acceptor. However, in the media containing 30% (v/v) acetone, dioxane,
      N,N-dimethylformamide, or dimethyl sulfoxide with 0.5 M GlcNAc as acceptor, the
      transglycosylation attained yields of 89, 13, 28, and 75%, respectively, as
      analyzed by high performance anion exchange chromatography. The enzyme was stable
      in media containing up to 30% acetone, 30% dimethyl sulfoxide, or 20% N,N
      dimethylformamide at 37 degrees C for at least 30 min. The acceptor (GlcNAc)
      concentration must be greater than 0.2 M for efficient transglycosylation.
      Electrospray mass spectrometry analysis of the transglycosylation product
      obtained in 30% acetone with Man5GlcNAc2Asn as donor and methyl alpha-2-acetamido
      2-deoxy-D-glucopyranoside as acceptor showed a mass ion of m/z 1249.4, consistent
      with the expected molecular weight. Analysis by 1H NMR of the product revealed
      that transglycosylation occurred at the C-4 of GlcNAc and the linkage was of the
      beta-configuration. In the acetone-containing medium, Glc, Man, 2-deoxy-Glc, and
      methyl alpha-D-GlcNAc can serve as a good acceptor as GlcNAc. Less favorable
      acceptors are xylose, fructose, 6-deoxy-Glc, and 3-O-methyl-D-glucose. On the
      other hand, GalNAc, Gal, allose, and 3-deoxy-Glc could not serve as acceptors of
      the enzyme transglycosylation.

PMID- 7629072
TI  - Synthesis of neoglycoconjugates by transglycosylation with Arthrobacter
      protophormiae endo-beta-N-acetylglucosaminidase. Demonstration of a macro-cluster
      effect for mannose-binding proteins.
AB  - The transglycosylation activity of endo-beta-N-acetylglucosaminidase from
      Arthrobacter protophormiae (endo-A) can be enhanced dramatically by inclusion of
      organic solvent in the reaction mixture (see accompanying article; Fan, J.-Q.,
      Takegawa, K., Iwahara, S., Kondo, A., Kato, I., Abeygunawardana, C., and Lee, Y.
      C. (1995) J. Biol. Chem. 270, 17723-17729). This finding was extended to
      synthesis of important intermediates for preparation of neoglycoconjugates. When
      0.2 M GlcNAc-O-(CH2)6NH2, GlcNAc-O-CH2CH = CH2, GlcNAc-O-(CH2)3-CH = CH2, GlcNAc
      O-(CH2)3NHCOCH = CH2, GlcNAc-S-CH2CN, GlcNAc-S-(CH2)3CH3, or GlcNAc-S-CH2
      CONHCH2CH(OMe)2 were used as acceptors in 30% acetone-containing media, the
      transglycosylation was accomplished with about 80% yield. The transglycosylation
      yields to benzyl beta-GlcNAc (67%), 4-methyl-umbelliferyl beta-GlcNAc (66%), p
      nitrophenyl beta-GlcNAc (33%), and (GlcNAc-beta-S-CH2CH2CH2)2 (43%) were lower,
      because their poor solubilities allowed only 0.05 M or lower concentrations in
      the reaction mixture. A micromole-scale synthesis of Man9GlcNAc2-O-(CH2)3-NHCOCH
      = CH2 (Man9GlcNAc2-NAP) was accomplished with 90% yield, and the structure of the
      transglycosylation product was confirmed by 1H NMR. Man9GlcNAc2-NAP was co
      polymerized with acrylamide. The ratio of sugar side chain to acrylamide in this
      glycopolymer was 1:44 and the molecular weight of glycopolymer was estimated to
      be between 1,500,000 and 2,000,000 by high performance gel filtration
      chromatography. The glycopolymer was shown to be a much more efficient inhibitor
      of binding by recombinant rat mannose binding protein-carbohydrate recognition
      domains (MBP-CRD) from serum (I50 = 3.5 microM Man9GlcNAc2-sugar chain) and liver
      (I50 = 74.5 nM) than soybean agglutinin.

PMID- 7629073
TI  - Two naturally occurring mouse alpha-1,2-mannosidase IB cDNA clones differ in
      three point mutations. Mutation of Phe592 to Ser592 is sufficient to abolish
      enzyme activity.
AB  - In mammalian cells, alpha-1,2-mannosidases play an essential role in the early
      steps of N-linked oligosaccharide maturation. We previously reported (Herscovics,
      A., Schneikert, J., Athanassiadis, A., and Moremen, K. W. (1994) J. Biol. Chem.
      269, 9864-9871) the isolation of mouse alpha-mannosidase IB cDNA clones from a
      Balb/c 3T3 cDNA library. Clone 4 encodes a type II membrane protein of 641 amino
      acids with a cytoplasmic tail of 35 amino acids, followed by a transmembrane
      domain and a large C-terminal catalytic domain, whereas clone 16 encodes only the
      last 471 amino acids. Their overlapping sequences (from amino acid 152) are
      identical, except for three point mutations that result in three amino acid
      differences in the catalytic domain of the enzyme (Thr411, Leu468, and Ser592 in
      clone 4 to Met411, Phe468, and Phe592 in clone 16, respectively). Both sequences
      could be amplified by polymerase chain reaction using templates of cDNAs derived
      from colon and brain of CD1 mice and from L cells derived from the C3H/An mouse,
      indicating that both are natural isoforms found in two inbred and one outbred
      mouse strains. When expressed in COS7 cells as a secreted protein A fusion
      protein, the catalytic domain of clone 16 displays alpha-1,2-mannosidase activity
      using [3H]mannose-labeled Man9GlcNAc as substrate, but the corresponding region
      of clone 4 is poorly secreted under identical conditions. The contribution of
      each point mutation to this differential secretion and enzyme activity of the two
      fusion proteins was assessed by testing the six recombinants corresponding to all
      the possible sequence permutations. Mutation of Phe592 to Ser592, as found in
      clone 4, is sufficient to abolish alpha-1,2-mannosidase activity, whereas
      mutation of Met411 to Thr411 or of Phe468 to Leu468 affects secretion with
      relatively little effect on enzyme activity. Phe592 is part of a highly conserved
      region that seems important for enzyme activity of class 1 alpha-1,2
      mannosidases.

PMID- 7629074
TI  - Mapping of single amino acid residues required for selective activation of Gq/11
      by the m3 muscarinic acetylcholine receptor.
AB  - Each G protein-coupled receptor can interact only with a limited number of the
      many structurally similar G proteins expressed within a cell. This study was
      undertaken to identify single amino acids required for selectively coupling the
      m3 muscarinic acetylcholine receptor to G proteins of the Gq/11 family. To this
      goal, distinct intracellular segments/amino acids of the m3 receptor were
      systematically substituted into the structurally closely related m2 muscarinic
      receptor, which couples to Gi/o proteins, not Gq/11 proteins. The resultant
      mutant receptors were expressed in COS-7 cells and studied for their ability to
      induce agonist-dependent stimulation of phosphatidylinositol hydrolysis, a
      response known to be mediated by G proteins of the Gq/11 class. Using this
      approach, we were able to identify four amino acids in the second intracellular
      loop and four amino acids at the C terminus of the third intracellular loop of
      the m3 muscarinic receptor that are essential for efficient Gq/11 activation. We
      could demonstrate that these amino acids, together with a short segment at the N
      terminus of the third intracellular loop, fully account for the G protein
      coupling preference of the m3 muscarinic receptor. Taken together, our data
      strongly suggest that only a limited number of amino acids, located on different
      intracellular regions, are required to determine the functional profile of a
      given G protein-coupled receptor.

PMID- 7629075
TI  - Posttranscriptional modification of the central loop of domain V in Escherichia
      coli 23 S ribosomal RNA.
AB  - Knowledge of the sites, structures, and functional roles of posttranscriptional
      modification in rRNAs is limited, despite steadily accumulating evidence that
      rRNA plays a direct role in the peptidyl transferase reaction and that modified
      nucleotides are concentrated at the functional center of the ribosome. Using
      methods based on mass spectrometry, modifications have been mapped in Escherichia
      coli 23 S rRNA in the central loop of domain V, a region of established
      interaction between 23 S RNA and tRNA. Two segments of RNA were isolated
      following protection with oligodeoxynucleotides and nuclease digestion: residues
      2423-2473 (51-mer) and 2481-2519 (39-mer). Dihydrouridine was located at position
      2449, within the RNase T1 hydrolysis product 2448-ADAACAGp-2454, as evidenced by
      a molecular mass 2 daltons higher than the gene sequence-predicted mass. This
      nucleoside, which is nearly ubiquitous in tRNA (where it is involved in
      maintenance of loop structure), is two bases from A-2551, a previously determined
      site of interaction between 23 S RNA and the CCA-aminoacyl terminus of tRNA at
      the ribosomal P-site. The oligonucleotide 2496-CACmCUCGp-2502 was isolated and
      accurately mass measured, and its nucleoside constituents were characterized by
      high performance liquid chromatography-mass spectrometry; there was no evidence
      of modification at position 2501 as implied by earlier work. Using similar
      techniques, the modified adenosine at position 2503 was unambiguously determined
      to be 2-methyladenosine in the fragment 2503-m2A psi Gp-2505.

PMID- 7629076
TI  - Molecular cloning of an insect aminopeptidase N that serves as a receptor for
      Bacillus thuringiensis CryIA(c) toxin.
AB  - The Bacillus thuringiensis CryIA(c) insecticidal delta-endotoxin binds to a 120
      kDa glycoprotein receptor in the larval midgut epithelia of the susceptible
      insect Manduca sexta. This glycoprotein has recently been purified and identified
      as aminopeptidase N. We now report the cloning of aminopeptidase N from a M.
      sexta midgut cDNA library. Two overlapping clones were isolated, and their
      combined 3095-nucleotide sequence contains an open reading frame encoding a 990
      residue pre-pro-protein. The N-terminal amino acid sequence derived from the
      glycoprotein is present in the open reading frame, immediately following a
      predicted cleavable signal peptide and a pro-peptide. There are four potential N
      linked glycosylation sites. The C-terminal sequence contains a possible
      glycosylphosphatidylinositol (GPI) anchor signal peptide, which suggests that,
      unlike most other characterized aminopeptidases, the lepidopteran enzyme is
      anchored in the membrane by a GPI anchor. This was confirmed by partial release
      of aminopeptidase N activity from M. sexta midgut brush border membranes by
      phosphatidylinositol-specific phospholipase C. The deduced amino acid sequence
      shows significant similarity to the zinc-dependent aminopeptidase gene family,
      particularly in the region surrounding the consensus zinc-binding motif
      characteristic of these enzymes.

PMID- 7629077
TI  - Mosaicism in vacuolating cytotoxin alleles of Helicobacter pylori. Association of
      specific vacA types with cytotoxin production and peptic ulceration.
AB  - Approximately 50% of Helicobacter pylori strains produce a cytotoxin, encoded by
      vacA, that induces vacuolation of eukaryotic cells. Analysis of a clinically
      isolated tox- strain (Tx30a) indicated secretion of a 93-kDa product from a 3933
      base pair vacA open reading frame. Characterization of 59 different H. pylori
      isolates indicated the existence of three different families of vacA signal
      sequences (s1a, s1b, and s2) and two different families of middle-region alleles
      (m1 and m2). All possible combinations of these vacA regions were identified,
      with the exception of s2/m1 (p < 0.001); this mosaic organization implies that
      recombination has occurred in vivo between vacA alleles. Type s1/m1 strains
      produced a higher level of cytotoxin activity in vitro than type s1/m2 strains;
      none of 19 type s2/m2 strains produced detectable cytotoxin activity. The
      presence of cagA (cytotoxin-associated gene A) was closely associated with the
      presence of vacA signal sequence type s1 (p < 0.001). Among patients with past or
      present peptic ulceration, 21 (91%) of 23 harbored type s1 strains compared with
      16 (48%) of 33 patients without peptic ulcers; only 2 (10%) of 19 subjects
      harboring type s2 strains had past or present peptic ulcers (p < 0.005). Thus,
      specific vacA genotypes of H. pylori strains are associated with the level of in
      vitro cytotoxin activity as well as clinical consequences.

PMID- 7629078
TI  - Identification of an elastin cross-linking domain that joins three peptide
      chains. Possible role in nucleated assembly.
AB  - The alignment of elastin molecules in the mature elastic fiber was investigated
      by purifying and sequencing cross-link-containing peptides generated by
      proteolytic digestion incompletely cross-linked insoluble elastin. Peptides of
      interest were purified by reverse phase and size exclusion high performance
      liquid chromatography and characterized by amino acid analysis and protein
      sequencing. One peptide, consisting of the cross-linking domain encoded by exon
      10, contained a modified lysine residue that had not condensed to form a
      polyfunctional cross-link. Although this domain contains the characteristic
      paired lysine residues found in other cross-linking domains of elastin, protein
      sequence analysis indicated that the first but not the second lysine had been
      oxidized by lysyl oxidase. This finding suggests that lysine residues in an
      individual cross-linking domain may not have equal susceptibility to oxidation by
      lysyl oxidase. In a second peptide, we found that a major cross-linking site in
      elastin is formed through the association of sequences encoded by exons 10, 19,
      and 25 and that the three chains are joined together by one desmosine and two
      lysinonorleucine cross-links. Past structural studies and computer modeling
      predict that domains 19 and 25 are linked by a desmosine cross-link, while domain
      10 bridges domains 19 and 25 through lysinonorleucine cross-links. These
      findings, together with the high degree of sequence conservation for these three
      domains, suggest an important function for these regions of the molecule,
      possibly nucleating the aggregation and polymerization of tropoelastin monomers
      in the developing elastic fiber.

PMID- 7629079
TI  - Specific association of CD63 with the VLA-3 and VLA-6 integrins.
AB  - We screened monoclonal antibodies to cell-surface proteins and selected an
      antibody, called 6H1, that recognizes a putative integrin-associated protein. The
      6H1 monoclonal antibody (mAb) indirectly coprecipitated alpha 3 beta 1 and/or
      alpha 6 beta 1, but not alpha 2 beta 1, or alpha 5 beta 1 from Brij 96 detergent
      lysates of multiple cell lines. Large scale purification using the 6H1 mAb
      yielded a single protein of 45-60 kDa with an amino-terminal sequence that
      exactly matched CD63. Confirming that the 6H1 mAb recognized the CD63 protein,
      6H1 and a known anti-CD63 mAb yielded identical coprecipitation results and
      identical colocalization into lysosomal granules containing cathepsin D.
      Furthermore, we used an established anti-CD63 mAb to detect this protein in an
      alpha 3 beta 1 immunoprecipitate, and also we observed VLA-3 and CD63
      colocalization in cellular "footprints." Notably, the cytoplasmic domain of alpha
      3 was neither required nor sufficient for CD63 association, suggesting that it
      occurred elsewhere within the alpha 3 beta 1 complex. Knowledge of these specific
      CD63-alpha 3 beta 1 and CD63-alpha 6 beta 1 biochemical associations should lead
      to critical insights into the specialized functions of alpha 3 beta 1, alpha 6
      beta 1, and CD63.

PMID- 7629080
TI  - The Escherichia coli PII signal transduction protein is activated upon binding 2
      ketoglutarate and ATP.
AB  - Nitrogen regulation of transcription in Escherichia coli requires sensation of
      the intracellular nitrogen status and control of the dephosphorylation of the
      transcriptional activator NRI-P. This dephosphorylation is catalyzed by the
      bifunctional kinase/phosphatase NRII in the presence of the dissociable PII
      protein. The ability of PII to stimulate the phosphatase activity of NRII is
      regulated by a signal transducing uridylyltransferase/uridylyl-removing enzyme
      (UTase/UR), which converts PII to PII-UMP under conditions of nitrogen
      starvation; this modification prevents PII from stimulating the dephosphorylation
      of NRI approximately P. We used purified components to examine the binding of
      small molecules to PII, the effect of small molecules on the stimulation of the
      NRII phosphatase activity by PII, the retention of PII on immobilized NRII, and
      the regulation of the uridylylation of PII by the UTase/UR enzyme. Our results
      indicate that PII is activated upon binding ATP and either 2-ketoglutarate or
      glutamate, and that the liganded form of PII binds much better to immobilized
      NRII. We also demonstrate that the concentration of glutamine required to inhibit
      the uridylyltransferase activity is independent of the concentration of 2
      ketoglutarate present. We hypothesize that nitrogen sensation in E. coli involves
      the separate measurement of glutamine by the UTase/UR protein and 2-ketoglutarate
      by the PII protein.

PMID- 7629081
TI  - Purification of recombinant porcine m2 muscarinic acetylcholine receptor from
      Chinese hamster ovary cells. Circular dichroism spectra and ligand binding
      properties.
AB  - The recombinant porcine m2 muscarinic acetylcholine receptor (rPm2R) from Chinese
      hamster ovary cells has been purified to homogeneity. Two mg of purified rPm2R,
      with a specific activity of 12 nmol of R-(-)-quinuclidinyl benzilate/mg of
      protein, were obtained from 30 ml of packed Chinese hamster ovary cells. The
      apparent molecular mass (78.5 kDa) and specific activity for the rPm2R
      preparation were the same as that for the Pm2R purified from atrial tissue, but
      the yield was 100 times greater. Purified rPm2R bound agonist and antagonist with
      the same affinities and coupled to the inhibitory guanine nucleotide-binding
      protein with the same efficiency as the purified native atrial Pm2R. Ligand
      binding studies were consistent with a single class of antagonist binding sites
      but two subclasses of agonist binding sites. The fraction of rPm2R having high
      affinity for agonists was increased by mM Mg2+, low detergent concentration, and
      low temperature. Circular dichroism spectra obtained for the purified rPm2R with
      and without agonists were indistinguishable, but spectra for the antagonist
      occupied receptor showed reproducibly deeper characteristic negative deflections
      at 208 and 220 nm. Secondary structure analysis of the CD spectra predicted 53%
      alpha-helix for the free receptor and 49% alpha-helix for the R-(-)-quinuclidinyl
      benzilate-receptor complex.

PMID- 7629082
TI  - Identification of a 40-kDa cell surface sialoglycoprotein with the
      characteristics of a major influenza C virus receptor in a Madin-Darby canine
      kidney cell line.
AB  - Infection of cells by influenza C virus is known to be initiated by virus
      attachment to cell surface glycoconjugates containing N-acetyl-9-O
      acetylneuraminic acid. Using an in vitro virus binding assay, we have detected
      this carbohydrate on several glycoproteins of Madin-Darby canine kidney cells
      (type I), a polarized epithelial cell line permissive for infection with
      influenza C virus. Among these proteins, only one was found to be present to a
      significant extent on the cell surface. This protein, gp40, was characterized as
      an O-glycosylated (mucin-type) integral membrane protein of 40 kDa, which was
      predominantly localized on the apical plasma membrane of filter-grown cells. It
      is a major cell surface sialoglycoprotein in this cell line and was shown to be
      subject to constitutive and rapid endocytosis. Thus, this glycoprotein can
      mediate not only the binding of influenza C virus to the cell surface, but also
      its delivery to endosomes, where penetration occurs by membrane fusion. Other
      highly sialylated cell surface glycoproteins were also detected but did not
      mediate influenza C virus binding to a significant extent, indicating that only
      gp40 contains 9-O-acetylated sialic acids.

PMID- 7629083
TI  - In vitro fusion of reticulocyte endocytic vesicles with liposomes.
AB  - Since reticulocytes have a high demand for iron, which is required for heme
      biosynthesis, these cells are highly specialized in the endocytosis of the iron
      carrier transferrin (Tf). From the resulting endocytic vesicles (EVs), iron is
      released and the vesicles rapidly return to the cell membrane where they fuse,
      causing the release of the apotransferrin. Due to a lack of other intracellular
      compartments, the endocytic vesicles can be readily isolated. In this study, we
      have investigated the fusogenic properties of EVs, using liposomes as target
      membranes. Membrane fusion was monitored by a lipid mixing assay based on the
      relief of fluorescence self-quenching, using octadecylrhodamine B-chloride (R18).
      Application of this procedure was verified and solidified by analysis of the
      fusion event by an independent lipid mixing assay, after in situ labeling of EVs,
      and by determination of the mixing of aqueous contents. We demonstrate that the
      endocytic vesicles are particularly prone to fuse with target membranes that
      contain dioleoylphosphatidylethanolamine (DOPE). Relative to DOPE, bilayers
      composed of phosphatidylserine or phosphatidylcholine show a reduced fusion
      activity with EV. The specific and strong inhibition of fusion by cyclosporin A
      and a peptide known to interfere with the propensity of DOPE to adopt the
      hexagonal HII phase suggests that the mechanism of fusion involves the ability of
      this lipid to readily adopt non-bilayer phases. ATP, GTP, and/or cytosol are not
      necessary to obtain fusion. However, trypsin treatment of the endocytic vesicles
      inhibits fusion, indicating the involvement of (a) protein(s) in the fusion
      event.

PMID- 7629084
TI  - The gene encoding human splicing factor 9G8. Structure, chromosomal localization,
      and expression of alternatively processed transcripts.
AB  - The 9G8 factor is a 30-kDa member of the SR splicing factor family. We report
      here the isolation and characterization of the human 9G8 gene. This gene spans
      7745 nucleotides and consists of 8 exons and 7 introns within the coding
      sequence, thus contrasting with the organization of the SC35/PR264 or RBP1 SR
      genes. We have located the human 9G8 gene in the p22-21 region of chromosome 2.
      The 5'-flanking region is GC-rich and contains basal promoter sequences and
      potential regulatory elements. Transfection experiments show that the 400-base
      pair flanking sequence has a promoter activity. Northern blot analysis of
      poly(A)+ RNA isolated from human fetal tissues has allowed us to identify five
      different species, generated by alternative splicing of intron 3, which may be
      retained or excised as a shorter version, as well as the use of two
      polyadenylation sites. We also show that the different isoforms are
      differentially expressed in the fetal tissues. The persistence of sequences
      between exon 3 and 4 results in the synthesis of a 9G8 protein lacking the SR
      domain which is expected to be inactive in constitutive splicing. Thus, our
      results raise the possibility that alternative splicing of intron 3 provides a
      mechanism for modulation of the 9G8 function.

PMID- 7629085
TI  - 2-Oxo-1,2-dihydroquinoline 8-monooxygenase, a two-component enzyme system from
      Pseudomonas putida 86.
AB  - 2-Oxo-1,2-dihydroquinoline 8-monooxygenase, which catalyzes the NADH-dependent
      oxygenation of 2-oxo-1,2-dihydroquinoline to 8-hydroxy-2-oxo-1,2
      dihydroquinoline, is the second enzyme in the quinoline degradation pathway of
      Pseudomonas putida 86. This enzyme system consists of two inducible protein
      components, which were purified, characterized, and identified as reductase and
      oxygenase. The yellow reductase is a monomeric iron-sulfur flavoprotein (M(r),
      38,000), containing flavin adenine dinucleotide and plant-type ferredoxin [2Fe
      2S]. It transferred electrons from NADH to the oxygenase or to some artificial
      electron acceptors. The red-brown oxygenase (M(r), 330,000) consists of six
      identical subunits (M(r), 55,000) and was identified as an iron-sulfur protein,
      possessing about six Rieske-type [2Fe-2S] clusters and additional iron. It was
      reduced by NADH plus catalytic amounts of reductase. For monooxygenase activity,
      reductase, oxygenase, NADH, molecular oxygen, and substrate were required. The
      activity was considerably enhanced by the addition of polyethylene glycol and
      Fe2+. 2-Oxo-1,2-dihydroquinoline 8-monooxygenase revealed a high substrate
      specificity toward 2-oxo-1,2-dihydroquinoline, since none of 25 other tested
      compounds was converted. Based on its physical, chemical, and catalytic
      properties, we presume 2-oxo-1,2-dihydroquinoline 8-monooxygenase to belong to
      the class IB multicomponent non-heme iron oxygenases.

PMID- 7629086
TI  - Effects of altered phosphorylation sites on the properties of CTP:phosphocholine
      cytidylyltransferase.
AB  - To investigate the role of phosphorylation and dephosphorylation in modulating
      the activity and location of CTP:phosphocholine cytidylyltransferase, we used
      site-directed mutagenesis to construct four mutant forms of cytidylyltransferase.
      These forms were 5SP-->AP, in which five of the seven Ser-Pro sequences were
      converted to Ala-Pro; 7SP-->AP, in which all of the seven Ser-Pro sequences
      converted to Ala-Pro; 16S-->A, in which all sixteen Ser residues that can be
      phosphorylated in wild type cytidylyltransferase were converted to Ala; and 16S-
      >E, in which all sixteen Ser residues were converted to Glu. The mutant enzymes
      were expressed in the strain 58 Chinese hamster ovary cell line, which is
      temperature-sensitive for growth and cytidylyltransferase activity. All mutant
      enzyme forms were enzymatically as active as the wild type when assayed under
      optimal conditions. In untreated cells, more of the Ser-->Ala mutants were
      membrane-associated than in cells expressing wild type enzyme, consistent with
      the phosphorylation state of the enzyme affecting its affinity for membranes.
      About half of the 16S-->A mutant remained soluble, however, indicating that
      dephosphorylation alone does not trigger membrane association. Although the
      amount of membrane-associated enzyme in the 16S-->A mutant was about 10-fold
      greater than that of wild type, phosphatidylcholine synthesis was increased by
      only about 75%, suggesting that membrane association does not necessarily cause
      full activation. All mutant forms, including the 16S-->E mutant, translocated to
      the particulate fraction upon oleate treatment, indicating that a high negative
      charge in the phosphorylation region does not preclude association of
      cytidylyltransferase with membranes. All mutant enzymes were able to support
      growth of strain 58 at 40 degrees C, and the rate of phosphatidylcholine
      synthesis was not greatly altered in the cell lines expressing mutant
      cytidylyltransferase forms. These results are consistent with a role for
      phosphorylation in the equilibrium distribution of cytidylyltransferase but
      suggest that changes in enzyme activity and location are not triggered
      exclusively by changes in the phosphorylation state.

PMID- 7629087
TI  - Plasma delivery of retinoic acid to tissues in the rat.
AB  - All-trans-retinoic acid (RA) activates ligand-dependent transcription factors
      that regulate retinoid-responsive gene expression. It is assumed that all-trans
      RA is formed within cells through in situ oxidation of retinol derived from the
      circulation. However, the circulation contains low levels of all-trans-RA
      (approximately 0.2-0.7% of that of plasma retinol). Our studies investigated the
      extent to which plasma all-trans-RA contributes to tissue pools of this retinoid
      and explored factors responsible for regulating its uptake by tissues and cells.
      Rats were continuously infused, to steady state, with all-trans-[3H]RA. From
      measures of specific activities of all-trans-[3H]RA at steady state, we
      determined that the preponderance of all-trans-RA in brain and liver was derived
      from the circulation. For six other tissues, approximately 10-30% of the retinoid
      was derived from the circulation, but pancreas and testis derived very little
      from the circulating pool. In other studies, we showed that retinoid nutritional
      status influences clearance of a bolus dose of all-trans-RA and that neither the
      rate of cellular all-trans-RA uptake nor its intracellular half-life is
      influenced by cellular lipid levels. Taken together, our data indicate that
      plasma all-trans-RA contributes to tissue pools of this retinoid and that
      specific and physiologically responsive cellular processes mediate its uptake.

PMID- 7629088
TI  - The type I collagen pro alpha 1(I) COOH-terminal propeptide N-linked
      oligosaccharide. Functional analysis by site-directed mutagenesis.
AB  - The C-propeptides of the pro alpha 1(I) and pro alpha 2(I) chains of type I
      collagen are each substituted with a single high-mannose N-linked
      oligosaccharide. Conservation of this motif among the fibrillar collagens has led
      to the proposal that the oligosaccharide has structural or functional importance,
      but a role in collagen biosynthesis has not been unambiguously defined. To
      examine directly the function of the pro alpha 1(I) C-propeptide N-linked
      oligosaccharide, the acceptor Asn residue was changed to Gln by site-directed
      mutagenesis. In transfected mouse Mov13 and 3T6 cells, unglycosylated mutant pro
      alpha 1(I) folded and assembled normally into trimeric molecules with pro alpha
      2(I). In biosynthetic pulse-chase experiments mutant pro alpha 1(I) were secreted
      at the same rate as wild-type chains; however, following secretion, the chains
      were partitioned differently between the cell layer and medium, with a greater
      proportion of the mutant pro alpha 1(I) being released into the medium. This
      distribution difference was not eliminated by the inclusion of yeast mannan
      indicating that the high-mannose oligosaccharide itself was not binding to the
      matrix or the fibroblast surface after secretion. Subtle alterations in the
      tertiary structure of unglycosylated C-propeptides may have decreased their
      affinity for a cell-surface component. Further support for a small conformational
      change in the mutant C-propeptides came from experiments suggesting that
      unglycosylated pro alpha 1(I) chains were cleaved in vitro by the purified C
      proteinase slightly less efficiently than wild-type chains. Mutant and normal pro
      alpha 1(I) were deposited with equal efficiency into the 3T6 cell accumulated
      matrix, thus the reduced cleavage by C-proteinase and altered distribution in the
      short pulse-chase experiments were not functionally significant in this in vitro
      extracellular matrix model system.

PMID- 7629089
TI  - Characterization of irreversible binding of beta-funaltrexamine to the cloned rat
      mu opioid receptor.
AB  - Binding of beta-funaltrexamine (beta-FNA) to the cloned rat mu opioid receptor
      expressed in COS-1 cells or Chinese hamster ovary cells was examined. beta-FNA
      bound to the mu receptor with high affinity. Irreversible binding of [3H]beta-FNA
      was defined as the binding that could not be dissociated by trichloroacetic acid.
      Na+ greatly enhanced the specific irreversible binding of [3H]beta-FNA to the mu
      receptor, which was concentration- and time-dependent. Specific irreversible
      binding of [3H]beta-FNA was potently inhibited by CTAP (a mu ligand), but not by
      ICI174,864 (a delta ligand) or U50,488H (a kappa ligand). These results indicate
      that [3H]beta-FNA binds irreversibly to the cloned mu opioid receptor. SDS
      polyacrylamide gel electrophoresis and fluorography showed that [3H]beta-FNA
      labeled receptors migrated as one broad and diffuse band with a mass of 80 kDa in
      Chinese hamster ovary or COS cells and as one band with a mass of 67 kDa in the
      rat brain preparation. Upon removal of N-linked carbohydrates, labeled receptors
      became a sharper band with a mass of approximately 40 kDa. [3H]beta-FNA did not
      bind irreversibly to the cloned rat kappa receptor. [3H]beta-FNA binding to four
      chimeric mu/kappa receptors was examined. The region from the middle of the third
      intracellular loop to the C terminus of the mu receptor is necessary for
      irreversible binding of beta-FNA.

PMID- 7629090
TI  - Prothrombinase components can accelerate tissue plasminogen activator-catalyzed
      plasminogen activation.
AB  - The enzymatic and cofactor subunits of human prothrombinase, factor Xa (FXa) and
      factor Va (FVa), respectively, were evaluated as modulators of Glu- and Lys
      plasminogen (Pg) activation by tissue plasminogen activator (tPA). The data
      revealed that both FXa and FVa could accelerate tPA activity by as much as 60
      fold for Lys-Pg and > 150-fold for Glu-Pg. This function of FVa depended on
      pretreatment with plasmin (Pn), whereas the FXa fibrinolytic cofactor activity
      was endogenous. In the native state, FVa was observed to inhibit the acceleration
      of Pn generation by FXa. These effects were dependent on Ca2+ and procoagulant
      phospholipid. Interactions between plasminogen and prothrombinase components were
      quantified. The apparent Kd for binding to FXa was 35 nM. Strikingly, the
      affinity between FVa and Pg was increased by approximately 2 orders of magnitude
      when the FVa was Pn-pretreated (Kd = 0.1 microM). These data cumulatively suggest
      a mechanism by which Pn production is coordinated with coagulation and localized
      to sites where procoagulant phospholipid is exposed on a cell surface.

PMID- 7629091
TI  - Ferredoxin-dependent redox system of a thermoacidophilic archaeon, Sulfolobus sp.
      strain 7. Purification and characterization of a novel reduced ferredoxin
      reoxidizing iron-sulfur flavoprotein.
AB  - To elucidate the ferredoxin-dependent redox system of the thermoacidophilic,
      aerobic archaeon Sulfolobus sp. strain 7, a novel FeS flavoprotein, which can
      reoxidize the reduced 7Fe ferredoxin in vitro, has been purified and
      characterized (designated as IFP) using the cognate 7Fe ferredoxin and 2
      oxoacid:ferredoxin oxidoreductase, a key enzyme of the archaeal tricarboxylic
      acid cycle. IFP consists of three non-identical subunits with apparent molecular
      masses of 87, 32, and 22 kDa, respectively, and contains at least two FMN (Em,
      6.8 = -57 mV) and two plant-ferredoxin-type [2Fe-2S]2+,1+ clusters (Em, 6.8 = 
      260 mV)/alpha 2 beta 2 gamma 2 structure. Both FeS and flavin centers of IFP are
      slowly but fully reduced by the enzymatically reduced cognate ferredoxin under
      anaerobic conditions at 50 degrees C, but not by NAD(P)H. Thus, the ferredoxin
      dependent redox system of Sulfolobus sp. strain 7 is tentatively proposed as
      follows: 2-oxoacid:ferredoxin oxidoreductase (thiamine pyrophosphate and [4Fe-4S]
      cluster)-->ferredoxin-->IFP ([2Fe-2S] cluster-->FMN).

PMID- 7629092
TI  - Influence of second and third cytoplasmic loops on binding, internalization, and
      coupling of chimeric bombesin/m3 muscarinic receptors.
AB  - In order to investigate the molecular basis for differences in the
      characteristics of bombesin (Bn) and m3 muscarinic cholinergic (m3 ACh)
      receptors, chimeric Bn receptors possessing cytoplasmic domains from the m3 ACh
      receptor were produced. The receptors were expressed in CHO-K1 cells and binding,
      structural, and signal transduction characteristics were analyzed. Cell lines
      bearing chimeric Bn receptors possessing m3 ACh receptor domains in place of
      either the second cytoplasmic loop (BM2L), the third cytoplasmic loop (BM3L), or
      both loops (BM23L) each bound 125I-bombesin with a single affinity that was
      approximately the same as that of the Bn receptor (5-10 nM). However, Bn
      receptors possessing the m3 ACh third cytoplasmic loop were severely affected in
      other respects. Internalization of ligand in Bn and BM2L cells was rapid and
      extensive (> 80% of bound 125I-bombesin was acid-resistant). In contrast,
      internalization was dramatically reduced in BM3L and BM23L cells (approximately
      20% of bound 125I-bombesin was acid-resistant). In Bn or BM2L cells 10 nM
      bombesin stimulated approximately 10-fold increases in phosphatidylinositol
      hydrolysis. Activation of Bn receptors also induced an increase in arachidonic
      acid release (478 +/- 32% of control, n = 3) and large increases in intracellular
      Ca2+. In contrast, in BM3L or BM23L cells, bombesin had no significant effect on
      phosphatidylinositol hydrolysis. Furthermore, BM3L receptor activation did not
      increase arachidonic acid release. However, BM3L and BM23L cells showed a small
      increase in intracellular Ca2+ at high concentrations of bombesin. These data
      indicate that the third cytoplasmic loop alone, or together with the second
      cytoplasmic loop, was not sufficient to transfer the characteristics of G protein
      interaction between m3 ACh and bombesin receptors. Furthermore, for the Bn
      receptor, ligand internalization does, whereas formation of the high affinity
      binding state does not, appear to require activation of G proteins.

PMID- 7629094
TI  - G protein regulation of the Na+/H+ antiporter in Xenopus laevis oocytes.
      Involvement of protein kinases A and C.
AB  - We have characterized the regulation of the endogenous Na+/H+ exchanger in
      Xenopus laevis oocytes by G proteins and protein kinases by measuring the
      ethylisopropylamiloride-sensitive Li+ uptake. Injection of oocytes with the
      stable GTP analog GTP gamma S stimulated Li+ uptake up to almost 4-fold, an
      effect blocked by coinjection with the GDP analog, guanyl-5'-yl thiophosphate.
      Injection into oocytes of beta gamma subunits of the heterotrimeric G protein
      transducin enhanced Li+ uptake by about 3-fold. This stimulation was blocked by
      transducin alpha subunits, which by themselves did not influence Li+ uptake.
      Using various activators and inhibitors of protein kinases, it is demonstrated
      that the X. laevis oocyte Na+/H+ antiporter can be stimulated by activation of
      both protein kinase A and C. Stimulation of Na+/H+ exchanger activity by GTP
      gamma S but not that induced by transducin beta gamma subunits was blocked by the
      protein kinase A inhibitor H-89. On the other hand, transducin beta gamma subunit
      stimulated activity was prevented by the protein kinase C inhibitor, calphostin
      C. The non-selective protein kinase inhibitor H-7 blocked both GTP gamma S- and
      transducin beta gamma subunit-stimulated Na+/H+ exchanger activity. The results
      suggest that the Na+/H+ exchanger of X. laevis oocytes can be activated by G
      proteins and that this activation is not direct but mediated by protein kinase A-
      and/or protein kinase C-dependent pathways.

PMID- 7629093
TI  - Partial characterization of the cytoplasmic domain of human kidney band 3.
AB  - The major anion exchanger in type A intercalated cells of the cortical and
      medullary collecting ducts of the human kidney is a truncated isoform of
      erythrocyte band 3 (AE1) that lacks the N-terminal 65 residues. Because this
      missing sequence has been implicated in the binding of ankyrin, protein 4.1,
      several glycolytic enzymes, hemoglobin, and hemichromes in erythrocytes, we have
      undertaken examination of the structure and peripheral protein interactions of
      this kidney isoform. The cytoplasmic domain of kidney band 3, kidney CDB3, was
      expressed in Escherichia coli and purified to homogeneity. The kidney isoform
      exhibited a circular dichroism spectrum and Stokes radius similar to its larger
      erythrocyte counterpart. Kidney CDB3 was also observed to engage in the same
      conformational equilibrium characteristic of erythrocyte CDB3. In contrast, the
      tryptophan and cysteine clusters of kidney CDB3 behaved very differently from
      erythrocyte CDB3 in response to pH changes and oxidizing conditions. Furthermore,
      kidney CDB3 did not bind ankyrin, protein 4.1, or aldolase, and expression of
      erythrocyte CDB3 was toxic to its bacterial host, whereas expression of kidney
      CDB3 was not. Taken together, these data suggest that the absence of the N
      terminal 65 amino acids in kidney CDB3 eliminates the major function currently
      ascribed to CDB3 in erythrocytes, i.e. that of peripheral protein binding. The
      primary function of residues 66-379 found in kidney CDB3 thus remains to be
      elucidated.

PMID- 7629095
TI  - Participation of the flank regions of the integration host factor protein in the
      specificity and stability of DNA binding.
AB  - The heterodimeric integration host factor (IHF) protein is a site-specific DNA
      binding protein from Escherichia coli that strongly bends the DNA. It has been
      proposed (Yang, C., and Nash, H.A. (1989) Cell 57, 869-880; Granston, A. E., and
      Nash, H. A. (1993) J. Mol. Biol 234, 45-59; Lee, E. C., Hales, L. M., Gumport, R.
      I., and Gardner, J. F. (1992) EMBO J. 11, 305-313) that the wrapping of the DNA
      around the protein is stabilized through interactions between the flanks of the
      protein and the DNA. In order to elucidate which domains of the IHF protein are
      involved in these interactions, we have constructed mutant proteins in which the
      C-terminal part of one of the subunits has been deleted. We observed that the C
      terminal alpha 3 helix of HimD is involved in the stability of DNA binding, but
      not in the specificity. In contrast the corresponding alpha 3 helix of HimA is
      essential for the sequence specificity, since an IHF mutant lacking this domain
      only binds to the DNA in a non-specific way. The possible role of the two C
      terminal alpha-helical structures in complex formation will be discussed. We also
      examined the properties of an IHF mutant that has an amino acid substitution
      between beta sheets beta 1 and beta 2 of the HimD subunit (R46H). The occupancy
      of the ihf site by the mutant and wild type proteins differ in the 3' part of the
      ihf site and as a result the bend introduced in the DNA by the mutant protein is
      less pronounced. We propose that the arginine 46 in the HimD subunit is in
      vicinity of the TTR region of the consensus and that through contacts within the
      minor groove the DNA bend introduced by IHF is stabilized.

PMID- 7629096
TI  - Transcriptional silencer of the Wilms' tumor gene WT1 contains an Alu repeat.
AB  - Expression of the Wilms' tumor gene WT1 is tightly regulated throughout
      development. In contrast, the WT1 promoter is promiscuous, functioning in all
      cell lines tested. We have cloned a transcriptional silencer that is involved in
      regulation of the WT1 gene. The transcriptional silencer is located in the third
      intron of the WT1 gene, approximately 12 kilobases from the promoter, and
      functions to repress transcription from the WT1 promoter in cell lines of non
      renal origin. The 460-base pair silencer region is unusual in that it contains a
      full-length Alu repeat. We have also cloned an enhancer like-element located 1.3
      kilobases upstream of the WT1 promoter.

PMID- 7629097
TI  - Ryanodine receptor-ankyrin interaction regulates internal Ca2+ release in mouse T
      lymphoma cells.
AB  - In this study, we have identified and partially characterized a mouse T-lymphoma
      ryanodine receptor on a unique type of internal vesicle which bands at the
      relatively light density of 1.07 g/ml. Analysis of the binding of [3H]ryanodine
      to these internal vesicles reveals the presence of a single, low affinity binding
      site with a dissociation constant (Kd) of 200 nM. The second messenger, cyclic
      ADP-ribose, was found to increase the binding affinity of [3H]ryanodine to its
      vesicle receptor at least 5-fold (Kd approximately 40 nM). In addition, cADP
      ribose appears to be a potent activator of internal Ca2+ release in T-lymphoma
      cells and is capable of overriding ryanodine-mediated inhibition of internal Ca2+
      release. Immunoblot analyses using a monoclonal mouse antiryanodine receptor
      antibody indicate that mouse T-lymphoma cells contain a 500-kDa polypeptide
      similar to the ryanodine receptor found in skeletal muscle, cardiac muscle, and
      brain tissues. Double immunofluorescence staining and laser confocal microscopic
      analysis show that the ryanodine receptor is preferentially accumulated
      underneath surface receptor-capped structures. T-lymphoma ryanodine receptor was
      isolated (with an apparent sedimentation coefficient of 30 S) by extraction of
      the light density vesicles with 3-[(3-cholamidopropyl)dimethylammonio]-1
      propanesulfonic acid (CHAPS) in 1 M NaCl followed by sucrose gradient
      centrifugation. Further analysis indicates that specific, high affinity binding
      occurs between ankyrin and this 30 S lymphoma ryanodine receptor (Kd = 0.075 nM).
      Most importantly, the binding of ankyrin to the light density vesicles
      significantly blocks ryanodine binding and ryanodine-mediated inhibition of
      internal Ca2+ release. These findings suggest that the cytoskeleton plays a
      pivotal role in the regulation of ryanodine receptor-mediated internal Ca2+
      release during lymphocyte activation.

PMID- 7629098
TI  - Modulation of chromatin folding by histone acetylation.
AB  - A homogeneous oligonucleosome complex was prepared by reconstitution of highly
      hyperacetylated histone octamers onto a linear DNA template consisting of 12
      tandemly arranged 208-base pair fragments of the 5 S rRNA gene from the sea
      urchin Lytechinus variegatus. The ionic strength-dependent folding of this
      oligonucleosome assembly was monitored by sedimentation velocity and electron
      microscopy. Both types of analysis indicate that under ionic conditions
      resembling those found in the physiological range and in the absence of histone
      H1, the acetylated oligonucleosome complexes remain in an extended conformation
      in contrast to their nonacetylated counterparts. The implications of this finding
      in the context of a multistate model of chromatin folding (Hansen, J. C., and
      Ausio, J. (1992) TIBS 197, 187-191) as well as its biological relevance are
      discussed.

PMID- 7629099
TI  - Location of the major epsilon-(gamma-glutamyl)lysyl cross-linking site in
      transglutaminase-modified human plasminogen.
AB  - Tissue and plasma transglutaminases cross-link human plasminogen into high
      molecular weight complexes (Bendixen, E., Borth, W., and Harpel, P. C. (1993) J.
      Biol. Chem. 268, 21962-21967). A major cross-linking site in plasminogen involved
      in the tissue transglutaminase-mediated polymerization process has been
      identified. The epsilon-(gamma-glutamyl)lysyl bridges of the polymer are formed
      between Lys-298 and Gln-322. Both the acyl donor Gln residue and the acyl
      acceptor Lys residue are located in the kringle 3 domain of plasminogen, i.e.
      cross-linking of plasminogen by tissue transglutaminase involves neither the
      catalytic domain nor the lysine-dependent binding sites of plasminogen. This
      study documents that kringle 3 contains a novel functional site with the
      potential to participate in transglutaminase-mediated cross-linking interactions
      with plasma, cell-surface, and extracellular proteins.

PMID- 7629100
TI  - Inhibition of an erythroid differentiation switch by the helix-loop-helix protein
      Id1.
AB  - The Id proteins function as negative regulators of basic-helix-loop-helix
      transcription factors, which play important roles in determination of cell
      lineage and in tissue-specific differentiation. Down-regulation of Id1 mRNA is
      associated with dimethyl sulfoxide-induced terminal differentiation of mouse
      erythroleukemia cells. To examine the significance of Id1 down-regulation in
      erythroid differentiation, we generated stable mouse erythroleukemia cell lines
      that constitutively express a "marked" form of the murine Id1 gene. Terminal
      erythroid differentiation was inhibited in these lines, as indicated by a block
      in activation of the erythroid-specific genes alpha-globin, beta-globin, and band
      3 and continued proliferation in the presence of dimethyl sulfoxide.
      Interestingly, this block occurred even in the presence of normal levels of the
      lineage-specific transcription factors GATA-1, NF-E2, and EKLF. Constitutive
      expression of Id1 did not interfere with DNase I hypersensitivity at site HS2 of
      the locus control region, expression of the erythropoietin receptor gene, or down
      regulation of the endogenous Id1 or c-myc genes. The differentiation block is
      reversible in these lines and can be rescued by fusion with human erythroleukemia
      cells. These findings suggest that in vivo, Id1 functions as an antagonist of
      terminal erythroid differentiation.

PMID- 7629101
TI  - Two SH2 domains of p120 Ras GTPase-activating protein bind synergistically to
      tyrosine phosphorylated p190 Rho GTPase-activating protein.
AB  - p120 GTPase-activating protein (GAP) is a negative regulator of Ras that
      functions at a key relay point in signal transduction pathways that control cell
      proliferation. Among other proteins, p120 GAP associates with p190, a GAP for the
      Ras-related protein, Rho. To characterize the p120.p190 interaction further, we
      used bacterially expressed glutathione S-transferase fusion polypeptides to map
      the regions of p120 necessary for its interactions with p190. Our results show
      that both the N-terminal and the C-terminal SH2 domains of p120 are individually
      capable of binding p190 expressed in a baculovirus/insect cell system. Moreover,
      the two SH2 domains together on one polypeptide bind synergistically to p190, and
      this interaction is dependent on tyrosine phosphorylation of p190. In addition,
      mutation of the highly conserved Arg residues in the critical FLVR sequences of
      both SH2 domains of full-length p120 reduces binding to tyrosine-phosphorylated
      p190. The dependence on p190 phosphorylation for complex formation with p120 SH2
      domains observed in vitro is consistent with analysis of the native p120.p190
      complexes formed in vivo. These findings suggest that SH2-phosphotyrosine
      interaction is one mechanism by which the cell regulates p120.p190 association
      and thus may be a means for coordinating the Ras- and Rho-mediated signaling
      pathways.

PMID- 7629102
TI  - Phosphorylation and desensitization of the human beta 1-adrenergic receptor.
      Involvement of G protein-coupled receptor kinases and cAMP-dependent protein
      kinase.
AB  - Persistent stimulation of the beta 1-adrenergic receptor (beta 1AR) engenders,
      within minutes, diminished responsiveness of the beta 1 AR/adenylyl cyclase
      signal transduction system. This desensitization remains incompletely defined
      mechanistically, however. We therefore tested the hypothesis that agonist-induced
      desensitization of the beta 1AR (like that of the related beta 2AR) involves
      phosphorylation of the receptor itself, by cAMP-dependent protein kinase (PKA)
      and the beta-adrenergic receptor kinase (beta ARK1) or other G protein-coupled
      receptor kinases (GRKs). Both Chinese hamster fibroblast and 293 cells
      demonstrate receptor-specific desensitization of the beta 1 AR within 3-5 min.
      Both cell types also express beta ARK1 and the associated inhibitory proteins
      beta-arrestin-1 and beta-arrestin-2, as assessed by immunoblotting. Agonist
      induced beta 1AR desensitization in 293 cells correlates with a 2 +/- 0.3-fold
      increase in phosphorylation of the beta 1AR, determined by immunoprecipitation of
      the beta 1AR from cells metabolically labeled with 32P(i). This agonist-induced
      beta 1AR phosphorylation derives approximately equally from PKA and GRK activity,
      as judged by intact cell studies with kinase inhibitors or dominant negative beta
      ARK1 (K220R) mutant overexpression. Desensitization, likewise, is reduced by only
      approximately 50% when PKA is inhibited in the intact cells. Overexpression of
      rhodopsin kinase, beta ARK1, beta ARK2, or GRK5 significantly increases agonist
      induced beta 1AR phosphorylation and concomitantly decreases agonist-stimulated
      cellular cAMP production (p < 0.05). Furthermore, purified beta ARK1, beta ARK2,
      and GRK5 all demonstrate agonist-dependent phosphorylation of the beta 1AR.
      Consistent with a GRK mechanism, receptor-specific desensitization of the beta
      1AR was enhanced by overexpression of beta-arrestin-1 and -2 in transfected 293
      cells. We conclude that rapid agonist-induced desensitization of the beta 1AR
      involves phosphorylation of the receptor by both PKA and at least beta ARK1 in
      intact cells. Like the beta 2AR, the beta 1AR appears to bind either beta
      arrestin-1 or beta-arrestin-2 and to react with rhodopsin kinase, beta ARK1, beta
      ARK2, and GRK5.

PMID- 7629103
TI  - CCAAT/enhancer-binding protein isoforms beta and delta are expressed in mammary
      epithelial cells and bind to multiple sites in the beta-casein gene promoter.
AB  - Lactogenic hormone-dependent expression of the rat beta-casein gene in mammary
      epithelial cells is controlled via a complex regulatory region in the promoter.
      The sequence between -176 and -82 is the minimal region to confer the response to
      glucocorticoid hormone and prolactin on a heterologous promoter. The response is
      further enhanced by the region between -282 and -176. DNase I footprinting
      experiments and electromobility shift assays revealed the presence of four
      binding sites for CCAAT/enhancer-binding protein (C/EBP) isoforms in the hormone
      response region between -220 and -132. In nuclear extracts from mammary
      epithelial cells, the prevalent C/EBP isoform binding to these sites is beta
      (C/EBP-beta). C/EBP-delta is also present in mammary epithelial cells, whereas
      C/EBP-alpha is not detectable. The C/EBP sites are located in close proximity to
      the previously characterized binding sites for the prolactin-inducible mammary
      gland factor/signal transducer and activator of transcription-5, the nuclear
      factor YY1, and the glucocorticoid receptor. The importance of the two proximal
      C/EBP binding sites at the 5' border of the minimal region was tested by
      mutational analysis. Mutations of each site were found to inhibit strongly both
      the basal and the lactogenic hormone-induced transcription of a beta-casein gene
      promoter chloramphenicol acetyltransferase construct. The results implicate
      C/EBPs as important regulators of beta-casein gene expression in the mammary
      epithelium.

PMID- 7629104
TI  - Hydrophobicity and subunit interactions of rod outer segment proteins
      investigated using Triton X-114 phase partitioning.
AB  - Triton X-114 phase partitioning, a procedure used for purifying integral membrane
      proteins, was used to study protein components of the mammalian visual
      transduction cascade. An integral membrane protein, rhodopsin, and two
      isoprenylated protein complexes, cyclic GMP phosphodiesterase and Gt beta gamma,
      partitioned into the detergent-rich phase. Arrestin, a soluble protein,
      accumulated in the aqueous phase. Gt alpha distributed about equally between
      phases whether GDP (Gt alpha.GDP) or GTP (Gt alpha.GTP) was bound. Gt beta gamma
      increased recovery of Gt alpha.GDP but not Gt alpha.GTP in the detergent phase.
      Trypsin-treated Gt alpha, which lacks the fatty acylated amino-terminal 2-kDa
      region, accumulated to a greater extent in the aqueous phase than did intact Gt
      alpha. Trypsinized cGMP phosphodiesterase, which lacks the isoprenyl group,
      partitioned into the aqueous phase. A carboxyl-terminal truncated mutant (Val-331
      stop) of Gt alpha accumulated more in the aqueous phase then did recombinant full
      length Gt alpha, supporting the role of the carboxyl terminus in increasing its
      hydrophobicity. N-Myristoylated recombinant Go alpha was more hydrophobic than
      recombinant Go alpha without myristate. ADP-ribosylation of Gt alpha catalyzed by
      NAD:arginine ADP-ribosyltransferase, but not by pertussis toxin, increased
      hydrophilicity. Triton X-114 phase partitioning can thus semiquantify the
      hydrophobic nature of proteins and protein domains. It may aid in evaluating
      changes associated with post-translational protein modification and protein
      protein interactions in a defined system.

PMID- 7629105
TI  - Primary structure, functional expression, and chromosomal localization of the
      bumetanide-sensitive Na-K-Cl cotransporter in human colon.
AB  - By moving chloride into epithelial cells, the Na-K-Cl cotransporter aids
      transcellular movement of chloride across both secretory and absorptive
      epithelia. Using cDNA probes from the recently identified elasmobranch secretory
      Na-K-Cl cotransporter (sNKCC1) (Xu, J. C., Lytle, C. Zhu, T. T., Payne, J. A.,
      Benz, E., and Forbush, B., III (1994) Proc. Natl. Acad. Sci. 91, 2201-2205), we
      have identified the human homologue. By screening cDNA libraries of a human
      colonic carcinoma line, T84 cell, we identified a sequence of 4115 bases from
      overlapping clones. The deduced protein is 1212 amino acids in length, and
      analysis of the primary structure indicates 12 transmembrane segments. The
      primary structure is 74% identical to sNKCC1, 91% identical to a mouse Na-K-Cl
      cotransporter (mNKCC1), 58% identical to rabbit and rat renal Na-K-Cl
      cotransporters (NKCC2), and 43% identical to the thiazide-sensitive Na-Cl
      cotransporters from flounder urinary bladder and rat kidney. Similar to sNKCC1
      and mNKCC1, the 5'-end of the human colonic cotransporter is rich in G + C
      content. Interestingly, a triple repeat (GCG)7 occurs within the 5'-coding region
      and contributes to a large alanine repeat (Ala15). Two sites for N-linked
      glycosylation are predicted on an extracellular loop between putative
      transmembrane segments 7 and 8. A single potential site for phosphorylation by
      protein kinase A is present in the predicted cytoplasmic C-terminal domain.
      Northern blot analysis revealed a 7.4-7.5-kilobase transcript in T84 cells and
      shark rectal gland and a approximately 7.2-kilobase transcript in mammalian
      colon, kidney, lung, and stomach. Metaphase spreads from lymphocytes were probed
      with biotin-labeled cDNA and avidin fluorescein (the cotransporter gene was
      localized to human chromosome 5 at position 5q23.3). Human embryonic kidney cells
      stably transfected with the full-length cDNA expressed a approximately 170-kDa
      protein recognized by anti-cotransporter antibodies. Following treatment with N
      glycosidase F, the molecular mass of the expressed protein was similar to that
      predicted for the core protein from the cDNA sequence (132-kDa) and identical to
      that of deglycosylated T84 cotransporter (approximately 135-kDa). The stably
      transfected cells exhibited a approximately 15-fold greater bumetanide-sensitive
      86Rb influx than control cells, and this flux required external sodium and
      chloride. Flux kinetics were consistent with an electroneutral cotransport of
      1Na:1K:2Cl. Preincubation in chloride-free media was necessary to activate fully
      the expressed cotransporter, suggesting a [Cl]-dependent regulatory mechanism.

PMID- 7629106
TI  - Deoxynucleoside induces neuronal apoptosis independent of neurotrophic factors.
AB  - Postmitotic sympathetic neurons are known to undergo a programmed cell death
      (apoptosis) when they are deprived of nerve growth factor (NGF) or treated with
      arabinofuranosyl nucleoside antimetabolites. Here we report the existence of a
      biochemical mechanism for the induction of neuronal death by an endogenous
      nucleoside in the presence of NGF. In support of such a mechanism we show that 2
      deoxyadenosine (dAdo) induces apoptosis in chick embryonic sympathetic neurons
      supported in culture by NGF, excess K+, phorbol 12,13-dibutyrate, or forskolin.
      Neuronal death was related to a dramatic increase in the dATP content of
      sympathetic neurons exposed to dAdo (34.96 +/- 5.98 versus 0.75 +/- 0.16
      pmol/micrograms protein in untreated controls, n = 9), implicating dATP in the
      toxicity. Supportive evidence for a central role of dATP was gained by inhibition
      of kinases necessary for phosphorylation of dAdo. 5'-Iodotubercidin in nanomolar
      concentrations completely and dose-dependently inhibited formation of dATP and
      also protected against toxicity of submillimolar concentrations of dAdo in
      sympathetic neurons. Although some of these actions of dAdo were remarkably
      similar to those reported for human lymphoid cells, several were uniquely
      different. For example, [3H]dAdo was not transported into neurons by the
      nucleoside transporter, and therefore inhibition of the transporter (dilazep,
      nitrobenzylthioinosine) did not prevent neurotoxicity by dAdo. Precursors of
      pyrimidine synthesis (2'-deoxycytidine, uridine) or NAD+ synthesis (nicotinamide)
      were ineffective in protecting sympathetic neurons against dAdo toxicity.
      Finally, inhibition of adenosine deaminase by deoxycoformycin or erythro-9-(2
      hydroxy-3-nonyl) adenine did not potentiate the toxic effects of dAdo. Our
      results provide evidence for the first time that neuronal cells are as
      susceptible to nucleoside lethality as human lymphocytes are, and provide a new
      model to study the salvage pathway of deoxyribonucleosides in controlling
      neuronal populations through programmed cell death.

PMID- 7629107
TI  - cDNA cloning, expression, mutagenesis, intracellular localization, and gene
      chromosomal assignment of mouse 5-lipoxygenase.
AB  - 5-Lipoxygenase of mouse macrophages and bone marrow-derived mast cells (BMMC) was
      investigated. Indirect immunocytofluorescence combined with confocal microscopy
      provided evidence for distinct intracellular expression patterns and trafficking
      of 5-lipoxygenase upon cellular activation. In resting BMMC, 5-lipoxygenase was
      found within the nucleus co-localizing with the nuclear stain Yo-Pro-1. When BMMC
      were IgE/antigen-activated the 5-lipoxygenase immunofluorescence pattern was
      changed from nuclear to perinuclear. The absence of divalent cations in the
      incubation medium, or calcium ionophore A23187 challenge, altered the
      predominantly nuclear expression pattern to new sites both cytosolic and
      intranuclear. The cDNA for murine macrophage 5-lipoxygenase was cloned by the
      polymerase chain reaction and would predict a 674 amino acid protein. Using
      control cells obtained from 5-lipoxygenase-deficient mice it was determined that
      a single isoform accounts for both soluble and membrane-bound and nuclear and
      cytosolic-localized enzyme in macrophages and BMMC. A mutation at amino acid 672
      (Val-->Met) introduced serendipitously during the cloning process was found to
      completely abolish 5-lipoxygenase enzyme activity when the enzyme was expressed
      in human embryonic kidney 293 cells. This subtle change is proposed to affect the
      ability of the COOH-terminal isoleucine to coordinate the essential non-heme iron
      atom. In macrophages and BMMC obtained from 5-lipoxygenase-deficient mice,
      compensatory changes in expression of genes involved in the biosynthesis of
      leukotriene B4 were investigated. 5-Lipoxygenase-activating protein expression
      was reduced by 50%, while leukotriene A4 hydrolase expression was unaltered. The
      5-lipoxygenase gene was mapped to the central region of mouse chromosome 6 in a
      region that shares homology with human chromosome 10 by interspecific backcross
      analysis. These studies provide a global picture of the murine 5-lipoxygenase
      system and raise questions about the role of 5-lipoxygenase and leukotrienes
      within the nucleus.

PMID- 7629108
TI  - Plasma membrane localization and functional rescue of truncated forms of a G
      protein-coupled receptor.
AB  - To test the hypothesis that G protein-coupled receptors consist of multiple
      autonomous folding domains, the rat m3 muscarinic acetylcholine receptor was
      "split" in all three intracellular (i1-i3) and all three extracellular loops (o2
      o4). The six resulting polypeptide pairs (Ni1.Ci1, No2.Co2, etc.) were
      coexpressed in COS-7 cells and studied for their ability to bind muscarinic
      ligands and to activate G proteins. In addition, immunocytochemical and ELISA
      studies were carried out to study the expression and subcellular localization of
      the individual receptor fragments. Interestingly, all N- and C-terminal receptor
      fragments studied (except Ni1, which contained only the first transmembrane
      domain) were found to be localized to the plasma membrane, even when expressed
      alone. Coexpression of three of the six polypeptide pairs, generated by splitting
      the m3 muscarinic receptor in the i2, o3, or i3 loop, resulted in receptor
      complexes (Ni2.Ci2, No3.Co3, and Ni3.Ci3, respectively), which were able to bind
      muscarinic agonists and antagonists with high affinity. The No3.Co3 and Ni3.Ci3
      polypeptide combinations, but not the Ni2.Ci2 complex, were also able to
      stimulate carbachol-dependent phosphatidyl inositol hydrolysis to a similar
      maximum extent as the wild type m3 muscarinic receptor. These findings strongly
      suggest that G protein-coupled receptors are composed of several independent
      folding units and may shed light on the molecular mechanisms governing receptor
      assembly and membrane insertion.

PMID- 7629109
TI  - N-terminal deletion mutants of insulin-like growth factor-II (IGF-II) show Thr7
      and Leu8 important for binding to insulin and IGF-I receptors and Leu8 critical
      for all IGF-II functions.
AB  - To define the role of the N-terminal region of insulin-like growth factor-II (IGF
      II) in its binding to insulin and IGF receptors, deletion mutants des-(1-5)-, des
      (1-7)-, and des-(1-8)-recombinant (r) IGF-II, and the Gly8 for Leu substitution
      mutant of rIGF-II were prepared by site-directed mutagenesis, expressed in
      Escherichia coli, and purified. The binding affinity and mitogenic activity of
      these rIGF-II mutants as well as commercially available des-(1-6)-rIGF-II were
      analyzed. While the relative affinity of des-(1-5)- and des-(1-6)-rIGF-II for
      purified human insulin and IGF-I receptors remained at > or = 50% levels of that
      of rIGF-II, the affinity of des-(1-7)-rIGF-II decreased to approximately 10% and
      approximately 3%, respectively, of that of rIGF-II. When the octapeptide
      including Leu8 was removed prior to the Cys9-Cys47 intrachain bond, the relative
      affinity of this deletion mutant, des-(1-8)-rIGF-II, for these receptors
      dramatically decreased to < 1% of that of rIGF-II. Substituting Gly8 for Leu in
      rIGF-II decreased the affinity of this mutant for the IGF-I and insulin receptors
      to about the same extent. These results suggest that the side chains of Thr7 and
      Leu8 may play an important role in retaining all of the IGF-II functions.
      Decreases in the relative affinity for binding of the mutants to these receptors
      paralleled the decreases in their mitogenic potency for cultured Balb/c 3T3
      cells. Although the relative affinity of des-(1-8)- or [Gly8]rIGF-II for rat IGF
      II/CIM6-P (cation-independent mannose 6-phosphate) receptors was also < 1% of
      that of rIGF-II, the relative affinities of des-(1-5)-, des-(1-6)-, and des-(1-7)
      rIGF-II for these receptors was significantly greater than that of rIGF-II. These
      results clearly demonstrate that Thr7 and Leu8 are important for binding to
      insulin and IGF-I receptors and Leu8 is critical for expression of all IGF-II
      functions.

PMID- 7629110
TI  - Structure, expression, and chromosomal assignment of the human gene encoding
      nuclear respiratory factor 1.
AB  - Nuclear respiratory factor 1 (NRF-1) is a transcription factor that acts on
      nuclear genes encoding respiratory subunits and components of the mitochondrial
      transcription and replication machinery. Here we describe the isolation and
      characterization of the human gene encoding NRF-1. The human genomic sequences
      detected with NRF-1 cDNA probes at high stringency are all contained within seven
      overlapping recombinant lambda clones. The NRF-1 gene encompassed by these
      recombinants spans approximately 65 kilobases (kb) and has 11 exons and 10
      introns that range in size from 0.8 to 15 kb. A rapid amplification of cDNA ends
      polymerase chain reaction product containing the 5'-terminus of the NRF-1 cDNA
      has two exons from the 5'-untranslated region and terminates at a major
      transcription initiation site identified by S1 nuclease mapping. A genomic
      fragment containing a portion of the 5'-terminal exon and an additional 1 kb
      upstream had a functional promoter that was active in transfected COS cells, HeLa
      cells, and L6 myoblasts. The transcription initiation site utilized by the
      transfected promoter corresponded to that used by the endogenous gene in vivo.
      NRF-1 mRNA was expressed at very low levels in rat tissues compared with
      cytochrome c and, unlike cytochrome c, was most abundantly expressed in lung and
      testis. The NRF-1 gene was localized to human chromosome 7 by analysis of DNA
      from a panel of human-hamster cell hybrids with human-specific NRF-1 polymerase
      chain reaction primers. This assignment was further refined to 7q31 by
      cohybridization of NRF-1- and chromosome 7-specific probes to human metaphase
      chromosomes. These analyses should be useful in evaluating the potential role of
      NRF-1 in mitochondrial diseases resulting from defects in the nuclear control of
      mitochondrial function.

PMID- 7629111
TI  - Highly active soluble processed forms of the transglutaminase 1 enzyme in
      epidermal keratinocytes.
AB  - The transglutaminase 1 (TGase 1) enzyme is required for the formation of a
      cornified cell envelope in epidermal keratinocytes. We show here that in addition
      to its membrane-anchored form, soluble forms of it are also important in
      keratinocytes. Proliferating cells contain soluble full-length enzyme of 106 kDa,
      but terminally differentiating cells contain a soluble 67-kDa form often
      complexed with a 33-kDa protein as well. The amino terminus of the 67 kDa form is
      residue 93 of the TGase 1 protein, corresponding to the site of proteolytic
      activation of the factor XIIIa TGase. The amino terminus of the 33-kDa protein is
      residue 573, corresponding to the site of a second proteolytic cleavage site of
      factor XIIIa, and of the site for proteolytic activation of the TGase 3 enzyme.
      The specific activity of the 67/33-kDa soluble complex is twice that of the
      soluble 67-kDa form and 10 times that of full-length TGase 1. The half-lives of
      the 67/33- and 106-kDa forms are about 7 or 20 h, respectively. Thus the TGase 1
      enzyme is complex, since it exists in keratinocytes as multiple soluble forms,
      either intact or proteolytically processed at conserved sites, and which have
      varying specific activities and likely functions.

PMID- 7629112
TI  - Characterization of the S3 subsite specificity of cathepsin B.
AB  - Five synthetic substrates containing different amino acid residues at the P3
      position (acetyl-X-Arg-Arg-AMC, where X is Gly, Glu, Arg, Val, and Tyr and where
      AMC represents 7-amindo-4-methylcoumarin) were used to investigate the S3 subsite
      specificity of cathepsin B. At pH 6.0, the specificity constant, kcat/Km, for
      tripeptide substrate hydrolysis was observed to increase in the order Glu < Gly <
      Arg < Val < Tyr. Molecular modeling studies of substrates containing a P3 Glu,
      Arg, or Tyr covalently bound as the tetrahedral intermediate to the enzyme
      suggest that the specificity for a P3 Tyr is because of a favorable aromatic
      aromatic interaction with Tyr75 on the enzyme as well as a possible H bond
      between the P3 Tyr hydroxyl and the side chain carboxyl of Asp69.

PMID- 7629113
TI  - Purification of an interleukin-1 beta converting enzyme-related cysteine protease
      that cleaves sterol regulatory element-binding proteins between the leucine
      zipper and transmembrane domains.
AB  - We describe the characterization and purification of a protease that cleaves
      sterol regulatory element-binding protein-1 (SREBP-1) and SREBP-2 in vitro.
      Cleavage occurs between the basic helix-loop-helix-leucine zipper and the first
      transmembrane domain of each SREBP. This is the region in which the SREBPs are
      cleaved physiologically by a sterol-regulated protease that releases an NH2
      terminal fragment that activates transcription of the genes for the low density
      lipoprotein receptor and 3-hydroxy-3-methylglutaryl CoA synthase. The cleavage
      enzyme, designated SREBP cleavage activity (SCA), belongs to a new class of
      cysteine proteases of the interleukin-1 beta-converting enzyme (ICE) family, all
      of which cleave at aspartic acid residues. Like ICE, SCA was inactive in cytosol,
      and it was activated in vitro by incubation at 30 degrees C. SCA was resistant to
      inhibitors of serine, aspartyl, and metalloproteases, but it was sensitive to N
      ethylmaleimide. The enzyme cleaved SREBP-1 and SREBP-2 between the Asp and Ser of
      a conserved sequence (S/DEPDSP). The activity was blocked by a tetrapeptide
      aldehyde, Ac-Asp-Glu-Ala-Asp-aldehyde (Ac-DEAD-CHO). A purified preparation of
      SCA from hamster liver contained a prominent 20-kDa polypeptide that could be
      labeled with [14C]iodoacetic acid. Labeling was blocked by Ac-DEAD-CHO. Partial
      amino acid sequence of this polypeptide revealed that it was the hamster
      equivalent of human CPP32, a putative protease whose cDNA was recently identified
      by virtue of sequence homology to ICE. CPP32 and ICE have been implicated in
      apoptosis in animal cells. Whether SCA/CPP32 participates in vivo in the sterol
      regulated activation of SREBP, or whether it activates SREBPs during apoptosis,
      remains to be determined.

PMID- 7629114
TI  - Conformational changes induced in the endoplasmic reticulum luminal domain of
      calnexin by Mg-ATP and Ca2+.
AB  - The type I membrane protein calnexin functions as a molecular chaperone for
      secretory glycoproteins in the endoplasmic reticulum with ATP and Ca2+ as two of
      the cofactors involved in substrate binding. Protease protection experiments with
      intact canine rough microsomes showed that amino acid residues 1-462 of calnexin
      are located within the lumen of the endoplasmic reticulum. Expression using the
      baculovirus Sf9 insect cell system of a recombinant truncated calnexin
      corresponding to residues 1-462 (calnexin delta TMC) revealed an association in
      vivo with a coexpressed secretory glycoprotein substrate, human immunodeficiency
      virus type I gp120. For the in vitro characterization of calnexin delta TMC, we
      purified this secreted form to homogeneity from the medium of Sf9 cells. We
      demonstrate that the properties of the purified calnexin delta TMC correspond to
      those of full-length calnexin in canine microsomes with at least one
      intramolecular disulfide bond and binding to 45Ca2+. Calnexin delta TMC underwent
      a marked and reversible conformational change following Ca2+ binding as measured
      by its resistance to proteinase K digestion of a 60-kDa fragment and also by the
      change from an oligomeric form of calnexin delta TMC to a monomeric form. We also
      found that calnexin bound Mg-ATP leading to a conformational change from a
      monomeric to an oligomeric form that coincided as with markedly increased
      proteinase sensitivity. Our results identify the luminal domain of calnexin as
      responsible for binding substrates, Ca2+, and Mg-ATP. Because Ca2+ and ATP are
      required in vivo for the maintenance of calnexin-substrate interactions,
      conformational changes in the luminal domain of calnexin induced by Ca2+ and Mg
      ATP are relevant to the in vivo function of calnexin as a molecular chaperone.

PMID- 7629115
TI  - Ca(2+)-dependent interaction of recoverin with rhodopsin kinase.
AB  - Recoverin (Rv) is a myristoylated Ca(2+)-binding protein present primarily in
      bovine photoreceptors. It represents a newly identified family of neuronal
      specific Ca(2+)-binding proteins that includes neurocalcin, hippocalcin, and
      guanylyl cyclase-activating protein. To investigate the function of Rv in
      photoreceptors, we identified proteins that bind immobilized Rv in a Ca(2+)
      dependent manner. Rhodopsin kinase (RK), interphotoreceptor retinoid-binding
      protein, and tubulin interact with Rv in the presence of Ca2+. The importance of
      the Rv/RK interaction was further characterized. RK, purified using immobilized
      Rv as an affinity matrix, catalyzed the light-dependent and Ca(2+)-independent
      incorporation of phosphates into rhodopsin when reconstituted with urea-stripped
      rod outer segment membranes. When only a small fraction (0.04%) of rhodopsin was
      photolyzed, as many as 700 phosphates were incorporated per photolyzed rhodopsin,
      a phenomenon known as "high gain" phosphorylation. When recoverin was added, the
      activity of RK became sensitive to free Ca2+, with EC50 = 3 microM. The N
      terminal myristoyl residue of Rv enhances the inhibitory effect of Rv and
      introduces cooperativity to the Ca(2+)-dependent inhibition of rhodopsin
      phosphorylation. Rv neither interacts with other members of the G-protein-coupled
      receptor kinase family such as beta-adrenergic receptor kinase 1 nor inhibits
      beta-adrenergic receptor kinase 1 activity. The specific and Ca(2+)-dependent
      Rv/RK interaction is necessary for the inhibitory effect of Rv on rhodopsin
      phosphorylation and may play an important role in photoreceptor light adaptation.

PMID- 7629116
TI  - Crystal structure of a cross-reaction complex between Fab F9.13.7 and guinea fowl
      lysozyme.
AB  - The crystal structure of the complex between the cross-reacting antigen Guinea
      fowl lysozyme and the Fab from monoclonal antibody F9.13.7, raised against hen
      egg lysozyme, has been determined by x-ray diffraction to 3-A resolution. The
      antibody interacts with exposed residues of an alpha-helix and surrounding loops
      adjacent to the lysozyme active site cleft. The epitope of lysozyme bound by
      antibody F9.13.7 overlaps almost completely with that bound by antibody HyHEL10;
      the same 12 residues of the antigen interact with the two antibodies. The
      antibodies, however, have different combining sites with no sequence homology at
      any of their complementarity-determining regions and show a dissimilar pattern of
      cross-reactivity with heterologous antigens. Side chain mobility of epitope
      residues contributes to confer steric and electrostatic complementarity to
      differently shaped combining sites, allowing functional mimicry to occur. The
      capacity of two antibodies that have different fine specificities to bind the
      same area of the antigen emphasizes the operational character of the definition
      of an antigenic determinant. This example demonstrates that degenerate binding of
      the same structural motif does not require the existence of sequence homology or
      other chemical similarities between the different binding sites.

PMID- 7629117
TI  - Probing the "message:address" sites for chemoattractant binding to the C5a
      receptor. Mutagenesis of hydrophilic and proline residues within the
      transmembrane segments.
AB  - The C5a anaphylatoxin ligand-receptor interaction on polymorphonuclear
      granulocytes stimulates chemotaxis, degranulation, and the oxidative burst. The
      receptor is a member of the large G-protein-coupled family. The ligand is a
      cationic peptide of 72 amino acids derived from the C5 component of complement
      and has been shown to have a number of structural requirements for interaction
      with the receptor. In order to probe the potential interaction sites between
      ligand and receptor, we constructed a series of mutated receptor molecules,
      targeting cysteines, prolines, and additional amino acids of interest because of
      combinations of charge or hydrophobicity and putative location with respect to
      the membrane. Transfected mutant receptors were analyzed for cell surface
      expression, ligand binding, and ligand-activated phospholipase C activity. The
      receptors created can be placed generally in four distinct classes: those which
      bind and signal like the natural receptor; those which bind but fail to transduce
      signals; those which are expressed but neither bind nor transduce signal; and
      those which are not expressed at the cell surface.

PMID- 7629118
TI  - Tyrosine phosphorylation of insulin receptor substrate-1 in vivo depends upon the
      presence of its pleckstrin homology region.
AB  - To characterize the structural basis for the interactions between the insulin
      receptor (IR) and its major substrate, insulin receptor substrate-1 (IRS-1), a
      segment of the NH2-terminal region of IRS-1 (Pro5-Pro65) was deleted. This region
      contains the first four conserved boxes of a pleckstrin homology (PH) domain,
      located at the NH2-terminal part of IRS-1. COS-7 cells were then cotransfected
      with the genes coding for IR and a wild-type (WT) or a mutated form of IRS-1. IRS
      1 delta PH underwent significantly reduced insulin-dependent tyrosine
      phosphorylation compared with WT IRS-1. The reduced in vivo tyrosine
      phosphorylation of IRS-1 delta PH was accompanied by reduced association between
      IRS-1 delta PH and its downstream effector p85 regulatory subunit of
      phosphatidylinositol-3 kinase. In contrast, both WT IRS-1 and IRS-1 delta PH
      underwent comparable insulin-dependent tyrosine phosphorylation in vitro when
      incubated with partially purified insulin receptor kinase. These findings suggest
      that the overall structure of IRS-1 is not altered by deletion of its PH domain
      and that the PH domain is not the main site for protein-protein interactions
      between the insulin receptor and IRS-1, at least in vitro. In conclusion, the PH
      region might facilitate in vivo binding of IRS-1 to membrane phospholipids or
      other cellular constituents in close proximity to the IR, whereas the actual
      interactions with the IR are presumably mediated through other domains of the IRS
      1 molecule. This could account for the fact that partial deletion of the PH
      domain selectively impairs the in vivo interactions between the insulin receptor
      and IRS-1, whereas their in vitro interactions remain unaffected.

PMID- 7629119
TI  - Association of native Ca2+ channel beta subunits with the alpha 1 subunit
      interaction domain.
AB  - beta Subunits of voltage-dependent Ca2+ channels play an important role in
      regulating Ca2+ channel function. The sites of alpha 1-beta subunit interaction
      have been localized recently to cytoplasmic domains of both subunits. The alpha 1
      subunit interaction domain (AID) is an 18-amino-acid conserved motif located
      between repeats I and II on all alpha 1 subunits which is essential for the
      binding of beta subunits. In order to further study the interaction of beta
      subunits with AID, we have expressed a 50-amino-acid glutathione S-transferase
      (GST) fusion protein from the alpha 1A subunit that contains the AID. Mutant GST
      fusion proteins that contain a single amino acid change (Y392S, Y392F, and Y392W)
      in the AIDA along with control GST were coupled to glutathione-Sepharose beads to
      form affinity beads. Binding assays using these affinity beads with in vitro
      synthesized 35S-labeled beta 2 and beta 3 subunits demonstrate that the hydroxyl
      group on tyrosine 392 of AIDA is critical for binding to beta subunits. The
      affinity bead assay was also used to identify and characterize native beta
      subunits from detergent extracts of different tissues. The AIDA affinity beads,
      but not the control or Y392S beads, specifically bind beta subunits from
      detergent extracts of skeletal muscle, cardiac muscle, and brain. Immunoblot
      analyses demonstrate the presence of beta 1a in skeletal muscle, beta 2 and beta
      3 in cardiac muscle, and beta 1b, beta 3, and beta 4 in brain. The assays also
      demonstrate the AIDA beads bind to beta subunits from tissue homogenates
      extracted with low salt and no detergent suggesting the existence of a pool of
      beta subunits which is not always associated with alpha 1 subunits. Also, beta
      subunits from solubilized skeletal muscle triads can be affinity-purified using
      AIDA CNBr-Sepharose. Our data demonstrate that the AID binds to native beta
      subunits from detergent and non-detergent tissue extracts illustrating that this
      domain on the alpha 1 subunit is the major anchoring site for the beta subunit.

PMID- 7629120
TI  - c-Jun N-terminal kinase but not mitogen-activated protein kinase is sensitive to
      cAMP inhibition in T lymphocytes.
AB  - The molecular mechanism underlying the cAMP inhibition of nuclear activation
      events in T lymphocytes is unknown. Recently, the activation of fibroblasts and
      muscle cells are shown to be antagonized by cAMP through the inhibition of
      mitogen-activated protein (MAP) kinases signaling pathway. Whether a similar
      antagonism may account for the late inhibitory effect of cAMP in T cell was
      examined. Surprisingly, extracellular signal regulated kinase 2 (ERK1, ERK2, and
      ERK3) of MAP kinase were poorly inhibited by cAMP. High concentration of cAMP
      also only weakly antagonized Raf-1 in T cells. The resistance of ERK and Raf-1 to
      cAMP clearly distinguishes T cells from fibroblasts. In contrast, another MAP
      kinase homologue c-Jun N-terminal kinase (JNK) was inhibited by cAMP in good
      correlation with that of IL-2 suppression. Moreover, JNK was antagonized by a
      delayed kinetics which is characteristic of cAMP inhibition. Despite that both
      ERK and JNK are essential for T cell activation, selective inhibition by cAMP
      further supports the specific role of JNK in T cell activation.

PMID- 7629121
TI  - An essential yeast gene encoding a homolog of ubiquitin-activating enzyme.
AB  - Ubiquitin (Ub) activation by the Ub-activating (E1) enzyme is the initial and
      essential step common to all of the known processes that involve post
      translational conjugation of Ub to itself or other proteins. The "activated" Ub,
      linked via a thioester bond to a specific cysteine residue in one of several Ub
      conjugating (E2) enzymes, which catalyze the formation of isopeptide bonds
      between the C-terminal glycine of Ub and lysine residues of acceptor proteins. In
      the yeast Saccharomyces cerevisiae, a 114-kDa E1 enzyme is encoded by an
      essential gene termed UBA1 (McGrath, J.P., Jentsch, S., and Varshavsky, A. (1991)
      EMBO J. 10, 227-236). We describe the isolation and analysis of another essential
      gene, termed UBA2, that encodes a 71-kDa protein with extensive sequence
      similarities to both the UBA1-encoded yeast E1 and E1 enzymes of other organisms.
      The regions of similarities between Uba1p and Uba2p encompass a putative ATP
      binding site as well as a sequence that is highly conserved between the known E1
      enzymes and contains the active-site cysteine of E1. This cysteine is shown to be
      required for an essential function of Uba2p, suggesting that Uba2p-catalyzed
      reactions involved a transient thioester bond between Uba2p and either Ub or
      another protein. Uba2p is located largely in the nucleus. The putative nuclear
      localization signal of Uba2p is near its C terminus. The Uba1p (E1 enzyme) and
      Uba2p cannot complement each others essential functions even if their subcellular
      localization is altered by mutagenesis. Uba2p appears to interact with itself and
      several other S. cerevisiae proteins with apparent molecular masses of 52, 63,
      87, and 120 kDa. Uba2p is multiubiquitinated in vivo, suggesting that at least a
      fraction of Uba2p is metabolically unstable. Uba2p is likely to be a component of
      the Ub system that functions as either an E2 or E1/E2 enzyme.

PMID- 7629122
TI  - Isolation of a functional homolog of the cell cycle-specific NIMA protein kinase
      of Aspergillus nidulans and functional analysis of conserved residues.
AB  - To investigate the degree of conservation of the cell cycle-specific NIMA protein
      kinase of Aspergillus nidulans, and to help direct its functional analysis, we
      cloned a homolog (designated nim-1) from Neurospora crassa. Over the catalytic
      domain NIM-1 is 75% identical to NIMA, but overall the identity drops to 52%. nim
      1 was able to functionally complement nimA5 in A. nidulans. Mutational analysis
      of potential activating phosphorylation sites found in NIMA, NIM-1, and related
      protein kinases was performed on NIMA. Mutation of threonine 199 (conserved in
      all NIMA-related kinases) inhibited NIMA beta-casein kinase activity and
      abolished its in vivo function. This site conforms to a minimal consensus
      phosphorylation site for NIMA (FXXT) and is analogous to the autophosphorylation
      site of cyclic-AMP-dependent protein kinases. However, mutation of a unique
      cysteine residue found only in the catalytic site of NIMA and NIM-1 had no effect
      on NIMA kinase activity or function. Three temperature-sensitive alleles of nimA
      that cause arrest in G2 were sequenced and shown to generate three different
      amino acid substitutions. None of the mutations prevented accumulation of NIMA
      protein during G2 arrest, but all prevented the p34cdc2/cyclin B-dependent
      phosphorylation of NIMA normally seen during mitotic initiation even though
      p34cdc2/cyclin B H1 kinase activity was fully activated.

PMID- 7629123
TI  - Peroxisome proliferator-activated receptor mediates cross-talk with thyroid
      hormone receptor by competition for retinoid X receptor. Possible role of a
      leucine zipper-like heptad repeat.
AB  - The peroxisome proliferator-activated receptors (PPAR) and thyroid hormone
      receptors (TR) are members of the nuclear receptor superfamily, which regulate
      lipid metabolism and tissue differentiation. In order to bind to DNA and activate
      transcription, PPAR requires the formation of heterodimers with the retinoid X
      receptor (RXR). In addition to activating transcription through its own response
      elements, PPAR is able to selectively down-regulate the transcriptional activity
      of TR, but not vitamin D receptor. The molecular basis of this functional
      interaction has not been fully elucidated. By means of site-directed mutagenesis
      of hPPAR alpha we mapped its inhibitory action on TR to a leucine zipper-like
      motif in the ligand binding domain of PPAR, which is highly conserved among all
      subtypes of this receptor and mediates heterodimerization with RXR. Replacement
      of a single leucine by arginine at position 433 of hPPAR alpha (L433R) abolished
      heterodimerization of PPAR with RXR and consequently its trans-activating
      capacity. However, a similar mutation of a leucine residue to arginine at
      position 422 showed no alteration of heterodimerization, DNA binding, or
      transcriptional activation. The dimerization deficient mutant L433R was no longer
      able to inhibit TR action, demonstrating that the selective inhibitory effect of
      PPAR results from the competition for RXR as well as possibly for other TR
      auxiliary proteins. In contrast, abolition of DNA binding by a mutation in the P
      box of PPAR (C122S) did not eliminate the inhibition of TR trans-activation,
      indicating that competition for DNA binding is not involved. Additionally, no
      evidence for the formation of PPAR:TR heterodimers was found in co
      immunoprecipitation experiments. In summary, we have demonstrated that PPAR
      selectively inhibits the transcriptional activity of TRs by competition for RXR
      and possibly non-RXR TR-auxiliary proteins. In contrast, this functional
      interaction is independent of the formation of PPAR:TR heterodimers or
      competition for DNA binding.

PMID- 7629124
TI  - The DNA binding activity of C/EBP transcription factor is regulated in the G1
      phase of the hepatocyte cell cycle.
AB  - We have isolated the promoter of the rat C/EBP alpha gene and find a high degree
      of homology with the mouse gene, particularly in putative regulatory domains.
      Transactivation of this promoter by ectopic expression of rat C/EBP beta occurs
      through a C/EBP regulatory domain at position -170 to -195. An oligonucleotide
      corresponding to this domain binds to complexes expressed in rat liver that
      comprise C/EBP alpha-C/EBP beta heterodimers (alpha beta) as well as C/EBP beta
      complexed with itself and/or other unidentified nuclear factors (beta 1, beta 2,
      and beta 3). The DNA binding activity of these complexes changes both
      qualitatively and quantitatively following partial hepatectomy. Within 2-5 h
      postsurgery, the binding activity of the alpha beta complexes drops severalfold,
      reaching a nadir by 20 h. During the ensuing 3-8 days, as regeneration nears
      completion, this activity slowly returns to normal quiescent liver levels.
      Western blot analysis shows 3 major C/EBP alpha polypeptide species (42, 40, and
      30 kDa), whose abundance in general parallels the decrease and recovery in DNA
      binding activity. In contrast to C/EBP alpha behavior, the DNA binding activity
      of the beta complexes is transiently induced severalfold during the early G1
      period between 2 and 6 h posthepatectomy. The major C/EBP beta polypeptide is the
      32-kDa LAP protein, whereas the LIP protein (21 kDa) is weakly expressed. Both
      remain essentially constant throughout the course of regeneration, suggesting
      that changes in DNA binding activity may reflect changes in the complexed
      proteins rather than the C/EBP beta polypeptides themselves. In primary
      hepatocyte cultures, under growth supporting conditions, in the absence of growth
      factors proliferation is negligible; C/EBP alpha is abundantly expressed at the
      outset, but is then extensively down-regulated. Epidermal growth factor causes
      further decay of C/EBP alpha polypeptides and DNA binding activity, and down
      regulates C/EBP beta DNA binding activity as well. Addition of transforming
      growth factor beta completely antagonizes the effects of epidermal growth factor
      on C/EBP beta activity, and partially overcomes the effect on C/EBP alpha. These
      results demonstrate that the DNA binding activity of C/EBP alpha and C/EBP beta
      complexes is regulated in the regenerating liver, and in hepatocyte cultures
      responding to growth factors that regulate their proliferation.

PMID- 7629125
TI  - RTG genes in yeast that function in communication between mitochondria and the
      nucleus are also required for expression of genes encoding peroxisomal proteins.
AB  - In Saccharomyces cerevisiae cells with dysfunctional mitochondria, such as in
      petites, the CIT2 gene encoding the peroxisomal glyoxylate cycle enzyme, citrate
      synthase 2 (CS2), is transcriptionally activated by as much as 30-fold, a
      phenomenon we call retrograde regulation. Two genes, RTG1 and RTG2, are required
      for both basal and elevated expression of CIT2 (Liao, X., and Butow, R. A. (1993)
      Cell 72, 61-71). Different blocks in the tricarboxylic acid cycle also elicit an
      increase in CIT2 expression, but not to the extent observed in petites. We have
      examined whether other genes of the glyoxylate cycle exhibit retrograde
      regulation and the role of RTG1 and RTG2 in their expression. Of the glyoxylate
      cycle genes tested, CIT2 is the only one that shows retrograde regulation,
      suggesting that CS2 may be an important control point for metabolic cross-feeding
      from the glyoxylate cycle to mitochondria. Surprisingly, RTG1 and RTG2 are
      required for efficient growth of cells on medium containing oleic acid, a
      condition which induces peroxisome biogenesis; these genes are also required
      together for oleic acid induction of three peroxisomal protein genes tested, POX1
      and CTA1 involved beta-oxidation of long chain fatty acids and PMP27, which
      encodes the most abundant protein of peroxisomal membranes. These data indicate
      that, in addition to their role in retrograde regulation of CIT2, the RTG genes
      are important for expression of genes encoding peroxisomal proteins and are thus
      key components in a novel, three-way path of communication between mitochondria,
      the nucleus, and peroxisomes.

PMID- 7629126
TI  - The unusual structure of a novel RNA replicon in rice.
AB  - A linear, plasmid-like, double-stranded RNA (dsRNA) was isolated from rice, and
      its entire sequence of 13,952 nucleotides (nt) was determined. The dsRNA encodes
      a single, unusually long, open reading frame (13,716 nt, 4,572 amino acid
      residues), which includes an RNA helicase-like domain and an RNA-dependent RNA
      polymerase-like domain. A series of Northern hybridization and primer extension
      experiments revealed that the coding (sense) strand of the dsRNA contains a
      discontinuity (nick) at a position 1,211 nt (or 1,256 nt) from the 5' end. This
      discontinuity divides not only the coding strand of dsRNA molecule into a 1,211
      nt fragment and a 12,741-nt fragment (or a 1,256-nt fragment and a 12,696-nt
      fragment) but also divides the long open reading frame into a 5' part of 1,045 nt
      (348 amino acid residues) and a 3' part of 12,671 nt (4,224 amino acid residues)
      or a 5' part of 1,090 nt (363 amino acid residues) and a 3' part of 12,626 nt
      (4,209 amino acid residues). It seems likely that almost all dsRNA molecules in
      rice plants contain such a discontinuity. This rice dsRNA appears to be a novel
      and unique RNA replicon.

PMID- 7629127
TI  - Identification and characterization of SNQ2, a new multidrug ATP binding cassette
      transporter of the yeast plasma membrane.
AB  - The SNQ2 gene of Saccharomyces cerevisiae, which encodes an ATP binding cassette
      protein responsible for resistance to the mutagen 4-nitroquinoline oxide, is
      regulated by the DNA-binding proteins PDR1 and PDR3. In a plasma membrane
      enriched fraction from a pdr1 mutant, the SNQ2 protein is found in the 160-kDa
      over-expressed band, together with PDR5. The SNQ2 protein was solubilized with n
      dodecyl beta-D-maltoside from the plasma membranes of a PDR5-deleted strain and
      separated from the PMA1 H(+/-)ATPase by sucrose gradient centrifugation. The
      enzyme shows a nucleoside triphosphatase activity that differs biochemically from
      that of PDR5 (Decottignies, A., Kolaczkowski, M., Balzi, E., and Goffeau, A.
      (1994) J. Biol. Chem. 269, 12797-12803) and is sensitive to vanadate, erythrosine
      B, and Triton X-100 but not to oligomycin, which inhibits the PDR5 activity only.
      Disruption of both PDR5 and SNQ2 in a pdr1 mutant decreases the cell growth rate
      and reveals the presence of at least two other ATP binding cassette proteins in
      the 160-kDa overexpressed band that have been identified by amino-terminal
      microsequencing.

PMID- 7629128
TI  - Functional characterization of the higher plant chloroplast chaperonins.
AB  - The higher plant chloroplast chaperonins (ch-cpn60 and ch-cpn10) have been
      purified and their structural/functional properties examined. In all plants
      surveyed, both proteins were constitutively expressed, and only modest increases
      in their levels were detected upon heat shock. Like GroEL and GroES of
      Escherichia coli, the chloroplast chaperonins can physically interact with each
      other. The asymmetric complexes that form in the presence of ADP are "bullet
      shaped" particles that likely consist of 1 mol each of ch-cpn60 and ch-cpn10. The
      purified ch-cpn60 is a functional molecular chaperone. Under "nonpermissive"
      conditions, where spontaneous folding was not observed, it was able to assist in
      the refolding of two different target proteins. In both cases, successful
      partitioning to the native state also required ATP hydrolysis and chaperonin 10.
      Surprisingly, however, the "double-domain" ch-cpn10, comprised of unique 21-kDa
      subunits, was not an obligatory co-chaperonin. Both GroES and a mammalian
      mitochondrial homolog were equally compatible with the ch-cpn60. Finally, the
      assisted-folding reaction mediated by the chloroplast chaperonins does not
      require K+ ions. Thus, the K(+)-dependent ATPase activity that is observed with
      other known groEL homologs is not a universal property of all chaperonin 60s.

PMID- 7629129
TI  - Two distinct signaling pathways activate the latent DNA binding function of p53
      in a casein kinase II-independent manner.
AB  - Post-translational modification of a carboxyl-terminal negative regulatory domain
      in vitro by either casein kinase II or protein kinase C allosterically activates
      the latent sequence-specific DNA binding function of p53. Reported here is a
      biochemical approach to determine the types of signaling pathways and enzymes
      that are involved in p53 activation in cells. Using a novel chromatographic
      method, we have been able to separate three distinct biochemical forms of p53
      that have been synthesized in vivo; two are in an activated state, and one is in
      a latent state for sequence-specific DNA binding. The two activated forms of p53
      appear to be controlled individually by either a constitutive or a UV-inducible
      signaling pathway. p53 lacking the COOH-terminal casein kinase II site (p53 delta
      4) was characterized biochemically and used to determine the affects of deletion
      of the casein kinase II motif on the production of the two activated forms of p53
      in vivo. As observed with full-length p53, the production of two distinct
      chromatographic forms of activated p53 delta 4 occurs in vivo, indicating that
      p53 activation can occur through a casein kinase II-independent pathway and
      suggesting that two other factors are involved in activation of p53 in vivo.

PMID- 7629130
TI  - Xenobiotic-inducible transcription of cytochrome P450 genes.

PMID- 7629131
TI  - Association of the interferon-dependent tyrosine kinase Tyk-2 with the
      hematopoietic cell phosphatase.
AB  - The tyrosine kinase Tyk-2 is physically associated with the Type I interferon
      (IFN) receptor complex and is rapidly activated during IFN alpha stimulation. We
      report that Tyk-2 forms stable complexes with the SH2-containing hematopoietic
      cell phosphatase (HCP) in several hematopoietic cell lines in vivo, and that the
      IFN alpha-induced tyrosine-phosphorylated form of Tyk-2 is a substrate for the
      phosphatase activity of HCP in in vitro assays. Furthermore, treatment of cells
      with the phosphatase inhibitor sodium orthovanadate induces tyrosine
      phosphorylation of Tyk-2 and an associated 115-kDa protein. Altogether, these
      data suggest that HCP regulates tyrosine phosphorylation of the Tyk-2 kinase, and
      thus its function may be important in the transmission of signals generated at
      the Type I IFN receptor level.

PMID- 7629132
TI  - A hPMS2 mutant cell line is defective in strand-specific mismatch repair.
AB  - Human cells contain several homologs of the bacterial mutL gene required for
      mismatch repair, including a gene on chromosome 7 designated hPMS2. We have
      identified an endometrial carcinoma cell line, HEC-1-A, that has a C-->T mutation
      in hPMS2 that generates a nonsense codon and yields a protein truncated at the C
      terminus. No wild-type gene or gene product was detected. The missing amino acids
      in hPMS2 are highly conserved among PMS homologs, suggesting that they may be
      critical for function. In support of this, extracts of HEC-1-A cells are
      defective in repairing a variety of mismatched substrates. Moreover, di-, tri-,
      and tetranucleotide repeated sequences are highly unstable in single cell clones
      of HEC-1-A cells, and HEC-1-A cells are resistant to killing by N-methyl-N'-nitro
      N-nitrosoguanidine. The results provide strong experimental support for the
      involvement of the hPMS2 gene product in mismatch repair in human cells and
      support the concept that a defective hPMS2 gene may lead to predisposition to
      certain forms of cancer.

PMID- 7629133
TI  - Thiophosphorylation of the 130-kDa subunit is associated with a decreased
      activity of myosin light chain phosphatase in alpha-toxin-permeabilized smooth
      muscle.
AB  - Pretreatment of alpha-toxin-permeabilized smooth muscle with ATP gamma S
      (adenosine 5'-O-(thiotriphosphate)) under conditions resulting in minimal (< 1%)
      thiophosphorylation of the myosin light chain increases the subsequent calcium
      sensitivity of force output and myosin light chain phosphorylation. The change in
      calcium sensitivity results at least in part from a 5-fold decrease in myosin
      light chain phosphatase activity. One of the few proteins thiophosphorylated
      under these conditions is the 130-kDa subunit of myosin light chain phosphatase.
      These results suggest that thiophosphorylation of this subunit leads to a
      decrease in the activity of the phosphatase, and that phosphorylation and
      dephosphorylation of the subunit may play a role in regulating myosin light chain
      phosphatase activity.

PMID- 7629134
TI  - Both p16 and p21 families of cyclin-dependent kinase (CDK) inhibitors block the
      phosphorylation of cyclin-dependent kinases by the CDK-activating kinase.
AB  - Phosphorylation of cyclin-dependent kinases (CDKs) by the CDK-activating kinase
      is required for the activation of CDK enzymes. Members of two families of CDK
      inhibitors, p16/p18 and p21/p27, become physically associated with and inhibit
      the activity of CDKs in response to a variety of growth-modulating signals. Here,
      we show that the representative members of both families of CDK inhibitors,
      p21waf1,cip1, p27kip1, and p18, can prevent the phosphorylation of their CDK
      partners, CDK2 and CDK6, by CDK-activating kinase. No direct interaction between
      CDK-activating kinase and the CDK inhibitors could be detected, suggesting that
      binding of these CDK inhibitors to CDK subunits renders CDK inaccessible to the
      CDK-activating kinase phosphorylation. These findings suggest that a general
      mechanism of CDK inhibitor function is to block the phosphorylation of CDK
      enzymes by CDK-activating kinase.

PMID- 7629135
TI  - Effect of cellular location on the function of ferrochelatase.
AB  - Ferrochelatase, the terminal enzyme of the heme biosynthetic pathway, is a
      nuclear encoded protein that is synthesized in the cytoplasm in a precursor form
      and then is translocated to the matrix side of the inner mitochondrial membrane.
      Since the product of the enzymatic reaction, protoheme IX, is utilized almost
      exclusively in the cytoplasmic compartment or on the cytoplasmic side of the
      inner mitochondrial membrane, it was of interest to determine if the
      intracellular location of ferrochelatase-deficient strain of the yeast
      Saccharomyces cerevisiae vectors that coded for full-length ferrochelatase and a
      truncated form of the enzyme that lacked the mitochondrial targeting sequence
      were expressed. Both of these transformed cells produce approximately equal total
      amounts of ferrochelatase, as determined by enzyme assays and Western blot
      analysis, but only with the full-length construct was ferrochelatase properly
      localized. In cells containing the truncated construct, ferrochelatase activity
      was found in all membrane fractions but was not located on the matrix side of the
      inner mitochondrial membrane. Cells containing either construct produced heme,
      although the amount of heme synthesized by cells with the truncated construct was
      significantly less. Interestingly in cells with improperly localized
      ferrochelatase the amount of b-type cytochrome decreased by 80% as opposed to c-
      and a-type cytochromes where the decreases were only 60 and 40%, respectively.

PMID- 7629136
TI  - Calcium binding in the pore of L-type calcium channels modulates high affinity
      dihydropyridine binding.
AB  - The pore-forming alpha 1 subunit of L-type voltage-gated Ca2+ channels contains a
      Ca(2+)-binding site that is allosterically coupled to the receptor site for
      dihydropyridine (DHP) Ca2+ antagonists. Site-directed mutations of conserved Phe
      and Glu residues in the pore-lining SS1/SS2 segments greatly reduced Ca2+
      enhancement of DHP binding. Substitution of Phe-1013 in the alpha 1 subunit from
      rabbit skeletal muscle (alpha 1S) with Gly (F1013G) as in DHP-insensitive Ca2+
      channels caused a 4-fold decrease in sensitivity to Ca2+. Mutation of the Ca(2+)
      binding residues Glu-1014 in domain III and Glu-1323 in domain IV to Gln (E1014Q
      and E1323Q) caused 11- and 35-fold decreases in sensitivity to Ca2+,
      respectively, as well as decreases in the maximal DHP binding affinities attained
      at optimal concentrations of Ca2+. DHP binding to the charge-reversal mutation,
      E1014K, had no sensitivity to Ca2+. Our results demonstrate that high affinity
      Ca2+ binding to the Glu residues in the SS1/SS2 segments of domains III and IV of
      alpha 1S stabilizes the DHP receptor site in its high affinity state. We propose
      a three-state model in which the affinity for DHPs is dependent on the presence
      of 0, 1, or 2 bound Ca2+ ions at sites in the pore.

PMID- 7629137
TI  - Electrospray ionization mass spectrometric determination of the complete
      polypeptide chain composition of Tylorrhynchus heterochaetus hemoglobin.
AB  - Electrospray ionization mass spectrometry (ESI-MS) of the native, reduced, and
      carbamidomethylated forms of the extracellular, 3.38-MDa hemoglobin from the
      marine polychaete Tylorrhynchus heterochaetus, when combined with a maximum
      entropy (MaxEnt) analysis, provided a complete description of the polypeptide
      chain composition. This hemoglobin, a hetero-multimeric complex of approximately
      180 polypeptide chains, consisting of globin and linker subunits in an
      approximately 3:1 mass ratio, is among the largest protein complexes investigated
      by ESI-MS. The globin subunits consist of a monomer subunit (chain I, 15575.4 Da)
      and a disulfide-bonded trimer subunit, 50068.4 Da, consisting of globin chains
      IIA (16601.9 Da), IIB (16680.4 Da), and IIC (16,794.0 Da). Linker subunits L1-L5,
      23233.8, 24835.4, 25326.9, 28202.2, and 26317.2 Da, respectively, were found
      together with a disulfide-bonded dimer of L2, 52609.4 Da. Using the exact masses
      of the subunits, a plausible model of the hemoglobin consisting of 144 globin
      chains (36 monomers and 36 trimers) and 36 linker chains provides a calculated
      mass of 3.42 MDa.

PMID- 7629138
TI  - Differential interactions of human Sos1 and Sos2 with Grb2.
AB  - The guanine nucleotide exchange factor Son of sevenless (Sos) performs a crucial
      step in the coupling of receptor tyrosine kinases to Ras activation. Mammalian
      cells contain two related but distinct Sos proteins, Sos1 and Sos2. Although they
      share a high degree of overall similarity, it is not known to what extent their
      biological and biochemical properties overlap. In the present study, we have
      compared the interactions of the two human homologues of Sos, hSos1 and hSos2,
      with the adaptor protein Grb2. We show that hSos2 interacts with Grb2 via its
      proline-rich COOH-terminal domain and that this interaction is dependent on the
      SH3 domains of Grb2. In general, these characteristics are similar to the ones
      reported previously for the interaction of hSos1 with Grb2. However, the apparent
      binding affinity of hSos2 for Grb2 is significantly higher relative to that of
      hSos1 both in vitro and in vivo. The region conferring this higher binding
      affinity has been mapped to residues 1126-1242 of the hSos2 COOH-terminal domain.
      These results suggest that Sos1 and Sos2 may differentially contribute to
      receptor-mediated Ras activation.

PMID- 7629139
TI  - The effect of botulinum neurotoxins on the release of insulin from the insulinoma
      cell lines HIT-15 and RINm5F.
AB  - Western blotting of the insulin-secreting beta-cell lines HIT-15 and RINm5F with
      anti-SNAP-25 (synaptosomal associated protein of 25 kDa), anti-synaptobrevin, and
      anti-syntaxin 1 antibodies revealed the presence of proteins with the same
      electrophoretic mobility as found in neural tissue. Permeabilization of both of
      these insulinoma cell lines to botulinum neurotoxin A by electroporation
      resulted, after 3 days of culture, in the loss of approximately 90% of SNAP-25
      immunoreactivity. A similar permeabilization of these cells with botulinum
      neurotoxin B resulted in the cleavage of approximately 90% of the synaptobrevin
      like immunoreactivities. Botulinum neurotoxin F also cleaved approximately 90% of
      the synaptobrevin-like immunoreactivity in RINm5F cells. The permeabilization of
      both insulinoma cells to neurotoxin A resulted in a > 90% inhibition of potassium
      stimulated, calcium-dependent insulin release. By contrast, permeabilization of
      the insulinoma cell lines to neurotoxin B resulted in only a approximately 60%
      inhibition of potassium-stimulated insulin release in HIT-15 cells, and neither
      neurotoxin B nor F caused inhibition in RINm5F cells. Thus HIT-15 and RINm5F
      cells contain the components of the putative exocytotic docking complex described
      in cells derived from the neural crest. In HIT-15 cells both SNAP-25 and
      synaptobrevin appear to be involved in calcium-dependent insulin secretion,
      whereas in RINm5F cells SNAP-25 but not synaptobrevin is involved.

PMID- 7629140
TI  - Evidence for a site-specific cytidine deamination reaction involved in C to U RNA
      editing of plant mitochondria.
AB  - Transcripts of higher plant mitochondria are modified post-transcriptionally by
      RNA editing. To distinguish between the mechanisms by which the cytidine to
      uridine transition could occur a combined transcription/RNA editing assay and an
      in vitro RNA editing system were investigated. Mitochondria isolated from
      etiolated pea seedlings and potato tubers were supplied with [alpha-32P]CTP to
      radiolabel the mitochondrial run-on transcripts. High molecular weight run-on
      transcripts were isolated and hydrolyzed, and nucleotide identities were analyzed
      by one- and two-dimensional thin layer chromatography. The amount of label
      comigrating with UMP nucleotides increases with extended incubation times.
      Analogous products were obtained by incubation of [alpha-32P]CTP or [5-3H]CTP
      radiolabeled in vitro transcripts with a mitochondrial lysate from pea
      mitochondria. 5-3H label of the cytosine base was detected in the UMP spot after
      incubation of in vitro transcripts with mitochondrial lysate. These results are
      consistent with a deamination reaction involved in this post-transcriptional C to
      U modification process. To prove that cytidines are deaminated specifically in
      vitro transcripts were reisolated after incubation and analyzed by reverse
      transcription-polymerase chain reaction. Sequence analysis clearly shows that
      only cytidines at editing sites are edited while residual cytidines are not
      modified and suggests that site-specific factors are involved in RNA editing of
      plant mitochondria.

PMID- 7629141
TI  - Biosynthesis of the macrolide oleandomycin by Streptomyces antibioticus.
      Purification and kinetic characterization of an oleandomycin glucosyltransferase.
AB  - The oleandomycin (OM) producer, Streptomyces antibioticus, possesses a mechanism
      involving two enzymes for the intracellular inactivation and extracellular
      reactivation of the antibiotic. Inactivation takes place by transfer of a glucose
      molecule from a donor (UDP-glucose) to OM, a process catalyzed by an
      intracellular glucosyltransferase. Glucosyltransferase activity is detectable in
      cell-free extracts concurrent with biosynthesis of OM. The enzyme has been
      purified 1,097-fold as a monomer, with a molecular mass of 57.1 kDa by a four
      step procedure using three chromatographic columns. The reaction operates via a
      compulsory-order mechanism. This has been shown by steady-state kinetic studies
      using either OM or an alternative substrate (rosaramycin) and dead-end
      inhibitors, and isotopic exchange reactions at equilibrium. OM binds first to the
      enzyme, followed by UDP-glucose. A ternary complex is thus formed prior to
      transfer of glucose. UDP is then released, followed by the glycosylated
      oleandomycin (GS-OM).

PMID- 7629142
TI  - The asparagine to aspartic acid substitution at position 276 of TEM-35 and TEM-36
      is involved in the beta-lactamase resistance to clavulanic acid.
AB  - TEM-35 (inhibitor resistant TEM (IRT)-4) and TEM-36 (IRT-7) clavulanic acid
      resistant beta-lactamases have evolved from TEM-1 beta-lactamase by two
      substitutions: a methionine to a leucine or a valine at position 69 and an
      asparagine to an aspartic acid at position 276. The substitutions at position 69
      have previously been shown to be responsible for the resistance to clavulanic
      acid, and they are the only mutations encountered in TEM-33 (IRT-5) and TEM-34
      (IRT-6). However, the N276D substitution has never been found alone in inhibitor
      resistant beta-lactamases, and its role in resistance to clavulanic acid was thus
      unclear. The N276D mutant was constructed, purified, and kinetically
      characterized. It was shown that the substitution has a direct effect on
      substrate affinities and leads to slightly decreased catalytic efficiencies and
      that clavulanic acid becomes a poor substrate of the enzyme. Electrospray mass
      spectrometry demonstrated the simultaneous presence of free and inhibited enzymes
      after incubation with clavulanic acid and showed that a cleaved moiety of
      clavulanic acid leads to the formation of the major inactive complex. The kinetic
      properties of the N276D mutant could be linked to a salt-bridge interaction of
      aspartic acid 276 with arginine 244 that alters the electrostatic properties in
      the substrate binding area.

PMID- 7629143
TI  - The cDNA sequence of human endothelial cell multimerin. A unique protein with
      RGDS, coiled-coil, and epidermal growth factor-like domains and a carboxyl
      terminus similar to the globular domain of complement C1q and collagens type VIII
      and X.
AB  - Multimerin is a massive, soluble protein found in platelets and in the
      endothelium of blood vessels. Multimerin is composed of varying sized, disulfide
      linked multimers, the smallest of which is a homotrimer. Multimerin is a factor
      V/Va-binding protein and may function as a carrier protein for platelet factor V.
      The cDNA for human multimerin was isolated from lambda gt11 endothelial cell
      libraries using antibodies, and the isolated cDNA clones were used to obtain the
      full sequence. The full-length multimerin cDNA was 4.2 kilobase pairs. Northern
      analyses identified a 4.7-kilobase transcript in cultured endothelial cells, a
      megakaryocytic cell line, platelets, and highly vascular tissues. The multimerin
      cDNA can encode a protein of 1228 amino acids with the probable signal peptide
      cleavage site between amino acids 19 and 20. The protein is predicted to be
      hydrophilic and to contain 23 N-glycosylation sites. The adhesive motif RGDS (Arg
      Gly-Asp-Ser) and an epidermal growth factor-like domain were identified. Sequence
      searches indicated that multimerin is a unique protein. Analyses identified
      probable coiled-coil structures in the central portion of the multimerin
      sequence. Additionally, the carboxyl-terminal region of multimerin resembles the
      globular, non-collagen-like, carboxyl-terminal domains of several other trimeric
      proteins, including complement C1q and collagens type VIII and X.

PMID- 7629144
TI  - Specific association of the beta isoform of the p85 subunit of
      phosphatidylinositol-3 kinase with the proto-oncogene c-cbl.
AB  - Phosphatidylinositol-3 kinase (PI-3 kinase) has been implicated in cellular
      events such as mitogenic signaling, actin organization, and receptor sorting. The
      p85 subunit of PI-3 kinase contains multiple domains capable of protein-protein
      interactions that may contribute to mediate the multiple physiological functions
      of this enzyme. Here, we demonstrate that antibodies raised against the p85
      subunit of PI-3 kinase immunoprecipitate a single tyrosine-phosphorylated protein
      of 120 kDa (pp120) from lysates of activated Jurkat T cells and A20 B cells. This
      protein is the only significant phosphotyrosine-containing protein in p85
      immunoprecipitates from these cells, and it cannot be detected in
      immunoprecipitates of other signaling proteins such as PLC gamma. Furthermore,
      antibodies specific for the beta isoform of p85 but not antibodies specific for
      the alpha isoform immunoprecipitate this tyrosine-phosphorylated protein. pp120
      completely comigrates with the proto-oncogene c-cbl, which is a 120 kDa protein
      product abundant in lymphoid cells. Furthermore, immunoblots of p85
      immunoprecipitates using antibodies raised against c-cbl detect a band at exactly
      the position of pp120. In addition, p85 can be detected in immunoblots of c-cbl
      immunoprecipitates. Thus, pp120 appears to correspond to c-cbl. A direct
      association between c-cbl and p85 can be observed in vitro using a fusion protein
      comprising the Src homology 2 (SH2) domains of p85, and this binding is abolished
      by phenyl phosphate, suggesting that the interaction is mediated through
      phosphotyrosine-SH2 domain interactions. Thus, these results show important
      functional differences between the alpha and beta isoforms of p85 in vivo and
      point to c-cbl as a potentially important mediator of some of the functions of PI
      3 kinase in intact cells.

PMID- 7629145
TI  - Expression and characterization of the 66-kilodalton (NQO3) iron-sulfur subunit
      of the proton-translocating NADH-quinone oxidoreductase of Paracoccus
      denitrificans.
AB  - The proton-translocating NADH-quinone oxidoreductase (NDH-1) of Paracoccus
      denitrificans is composed of at least 14 dissimilar subunits which are designated
      NQO1-14 and contains one noncovalently bound FMN and at least five EPR-visible
      iron-sulfur clusters (N1a, N1b, N2, N3, and N4) as prosthetic groups. Comparison
      of the deduced primary structures of the subunits with consensus sequences for
      the cofactor binding sites has predicted that NQO1, NQO2, NQO3, NQO9, and
      probably NQO6 subunits are cofactor binding subunits. Previously, we have
      reported that the NQO2 (25 kDa) subunit was overexpressed as a water-soluble
      protein in Escherichia coli and was found to ligate a single [2Fe-2S] cluster
      with rhombic symmetry (gx,y,z = 1.92, 1.95, and 2.00) (Yano, T., Sled', V.D.,
      Ohnishi, T., and Yagi, T. (1994) Biochemistry 33, 494-499). In the present study,
      the NQO3 (66 kDa) subunit, which is equivalent to the 75-kDa subunit of bovine
      heart Complex I, was overexpressed in E. coli. The expressed NQO3 subunit was
      found predominantly in the cytoplasmic phase and was purified by ammonium sulfate
      fractionation and anion-exchange chromatography. The chemical analyses and UV
      visible and EPR spectroscopic studies showed that the expressed NQO3 subunit
      contains at least two distinct iron-sulfur clusters: a [2Fe-2S] cluster with
      axial EPR signals (g perpendicular, parallel = 1.934 and 2.026, and L
      perpendicular parallel = 1.8 and 3.0 millitesla) and a [4Fe-4S] cluster with
      rhombic symmetry (gx,y,z = 1.892, 1.928, and 2.063, and Lx,y,z = 2.40, 1.55, and
      1.75 millitesla). The midpoint redox potentials of [2Fe-2S] and [4Fe-4S] clusters
      at pH 8.6 are -472 and -391 mV, respectively. The tetranuclear cluster in the
      isolated NQO3 subunit is sensitive toward oxidants and converts into [3Fe-4S]
      form. The assignment of these iron-sulfur clusters to those identified in the P.
      denitrificans NDH-1 enzyme complex and the possible functional role of the NQO3
      subunit is discussed.

PMID- 7629146
TI  - Lumenal Ca2+ dissociation from the phosphorylated Ca(2+)-ATPase of the
      sarcoplasmic reticulum is sequential.
AB  - Once two radioactive Ca2+ coming from the cytoplasm are bound to the transport
      sites of the nonphosphorylated ATPase, excess EGTA induces rapid dissociation of
      both ions, whereas excess nonradioactive Ca2+ only reaches one of the two bound
      Ca2+. This difference has been explained assuming that the two Ca2+ sites are in
      a single file channel in which the superficial Ca2+ is freely exchangeable from
      the cytoplasm, whereas the deeper Ca2+ is exchangeable only when the superficial
      site is vacant. The same experiment was done using phosphorylated ATPase to
      determine whether Ca2+ dissociation toward the lumen is sequential as well. Under
      conditions that allow ADP-sensitive phosphoenzyme to accumulate (leaky vesicles,
      5 degrees C, pH 8, 300 mM KC1), we found the same two pools of Ca2+. Excess EGTA
      induced dissociation of both ions together with dephosphorylation. Excess
      nonradioactive Ca2+ induced the exchange of half the radioactive Ca2+ without any
      effect on the phosphoenzyme level. Our results show a close similarity between
      the transport sites of the nonphosphorylated and the phosphorylated enzymes,
      although the orientation, affinities, and dissociation rate constants are
      different.

PMID- 7629147
TI  - Investigation of monovalent cation activation of S-adenosylmethionine synthetase
      using mutagenesis and uranyl inhibition.
AB  - S-Adenosylmethionine (AdoMet) synthetase catalyzes the formation of AdoMet from
      ATP and L-methionine with subsequent hydrolysis of the bound tripolyphosphate
      intermediate. Maximal activity requires the presence of two divalent and one
      monovalent cation per active site. Recently, the x-ray structure of the
      Escherichia coli AdoMet synthetase was solved, and the positions of the two Mg2+
      binding sites were identified. Based on additional spherical electron density,
      the K+ binding site was postulated to be a nearby site where the uranyl heavy
      atom derivative also bound in the crystal. The side chain of glutamate 42 is
      within ligation distance of the metals. Mutagenesis of glutamate 42 to glutamine
      (E42QMetK) abolished monovalent cation activation and produced an enzyme that has
      kinetic properties virtually identical to those of K(+)-free wild type AdoMet
      synthetase in both the overall AdoMet synthetase reaction and in the hydrolysis
      of tripolyphosphate. Thus, there is a approximately 100-fold decrease in the Vmax
      for AdoMet synthesis and large increases in the Km values for both substrates. In
      contrast there is only a 2-fold decrease in Vmax for tripolyphosphate hydrolysis.
      The uranyl ion, UO2(2+), is a competitive inhibitor with respect to K+ (Ki = 350
      nM) and is the first ion to bind at this site and inhibit the enzyme. The UO2(2+)
      inhibition is reversible and tight-binding, and results from UO2(2+) and not
      UO2(2+)-ATP. Analogous to K+ activation, UO2(2+) predominantly inhibits AdoMet
      formation rather than tripolyphosphate hydrolysis. The kinetic results indicate
      that UO2(2+) inhibition is likely to result from interference with productive ATP
      binding. UO2(2+) remains a tight-binding inhibitor of the E42Q mutant, which
      suggests that K+ and UO2(2+) have different ligation preferences when bound in
      the monovalent cation binding pocket. The results support the model that
      glutamate 42 provides ligands to the K+ and has a major role in monovalent cation
      binding.

PMID- 7629148
TI  - Induction of heparin-binding EGF-like growth factor expression during myogenesis.
      Activation of the gene by MyoD and localization of the transmembrane form of the
      protein on the myotube surface.
AB  - Heparin-binding epidermal growth factor-like growth factor (HB-EGF) gene
      expression and protein localization were analyzed during the process of myogenic
      differentiation. The mouse HB-EGF gene was isolated, and a 1.8-kilobase genomic
      fragment flanking the 5' end of the cDNA was cloned. This fragment contains two
      sequences which match the consensus CANNTG sequence for E-boxes, binding sites
      for the MyoD family of DNA-binding transcription factors that regulate
      myogenesis. Accordingly, HB-EGF synthesis was analyzed in 10T1/2 cells and C2C12
      cells which are used commonly for the study of myogenesis. HB-EGF gene expression
      was upregulated in both cell types during myogenesis. In 10T1/2 cells, direct
      activation of HB-EGF gene expression by MyoD was shown in that: i) transient
      transfection of these cells with a plasmid expressing MyoD resulted in a 10-20
      fold increase in endogenous HB-EGF mRNA levels; ii) co-transfection of MyoD and
      an HB-EGF promoter-reporter plasmid resulted in a 5-10-fold increase in reporter
      activity, an increase that was abrogated by deletion of a putative HB-EGF
      proximal E-box sequence; and iii) incubation of MyoD protein with a 25-base pair
      double-stranded oligonucleotide corresponding to the HB-EGF proximal E-box
      sequence resulted in retarded electrophoretic mobility of the oligonucleotide. In
      C2C12 cells, differentiation of myoblasts into myotubes resulted in a 40-50-fold
      increase in HB-EGF promoter activity. In addition, immunostaining and laser
      confocal microscopy detected HB-EGF protein in C2C12 myotubes but not in
      myoblasts. The HB-EGF produced was in its transmembrane form and localized to the
      myotube surface. Taken together, it was concluded that during skeletal muscle
      cell differentiation, MyoD plays a direct role in activating HB-EGF gene
      expression and that HB-EGF protein is expressed preferentially in myotubes and in
      its membrane-anchored form.

PMID- 7629149
TI  - A string of enzymes, purification and characterization of a fusion protein
      comprising the four subunits of the glucose phosphotransferase system of
      Escherichia coli.
AB  - A multidomain protein comprising the four subunits of the glucose
      phosphotransferase system of Escherichia coli was constructed by fusion of the
      transmembrane subunit IICBGlc and the three cytoplasmic proteins, IIAGlc, HPr,
      and enzyme I. The subunits were linked in the above order with Ala-Pro-rich
      linkers; the fusion protein was overexpressed in E. coli and purified by Ni2+
      chelate affinity chromatography. Approximately 3 mg of the fusion protein could
      be purified from 1 liter of culture. The phosphotransferase activity of the
      purified fusion protein was 3-4 times higher than that of an equimolar mixture of
      the isolated subunits. The mannose transporter, which also requires enzyme I and
      HPr, was not an effective competitor in the overall phosphoryltransfer reaction
      when the fusion protein was used, whereas it was a competitor when an equimolar
      mixture of the separate subunits was employed. Transphosphorylation activity of
      the fusion protein was almost indistinguishable from the wild-type IICBglc.
      Addition of extra IICBGlc subunit could significantly stimulate the
      phosphotransferase activity of the fusion protein, addition of extra IIAGlc
      subunit and enzyme I, in contrast, was slightly inhibitory, and HPr had almost no
      effect. An optimal detergent-lipid ratio is required for maximum activity of the
      fusion protein. Our results suggest that Ala-Pro-rich linker sequences may be of
      general use for the construction of catalytically active fusion proteins with
      novel properties.

PMID- 7629150
TI  - Epidermal growth factor and c-Jun act via a common DNA regulatory element to
      stimulate transcription of the ovine P-450 cholesterol side chain cleavage
      (CYP11A1) promoter.
AB  - The P-450 side chain cleavage (CYP11A1) gene encodes the enzyme that catalyzes
      the initial step in steroid biosynthesis, resulting in the conversion of
      cholesterol to pregnenolone. Expression of the CYP11A1 gene is increased by
      hormones, such as adrenocorticotropin and luteinizing hormone, as well as by a
      number of growth factors, suggesting that its promoter may contain regulatory
      elements that respond to multiple signal transduction pathways. Using transient
      expression assays of the ovine CYP11A1 promoter in JEG-3 placental cells,
      distinct regulatory elements were found to mediate transcriptional stimulation by
      cAMP and epidermal growth factor (EGF). The cAMP response was mediated through a
      GC-rich sequence localized between -117 and -92. In contrast, EGF induced CYP11A1
      transcription through an adjacent but distinct sequence (-92 to -77 base pairs)
      that was shown previously to bind nuclear proteins in DNase I footprinting
      reactions. This EGF-responsive element (EGF-RE) resembles an activator protein-1
      (AP-1) site and was also required for transactivation by co-transfected c-Jun. A
      point mutation within the EGF-RE impaired stimulation by both EGF and c-Jun,
      suggesting that these pathways converge on a common regulatory element. Transfer
      of single or multiple copies of the EGF-RE upstream of an heterologous promotor
      conferrd EGF and c-Jun responses, providing further evidence that this element is
      sufficient for both responses. Transfection studies employing mutant c-Jun
      proteins confirmed a requirement for its DNA binding, leucine zipper and amino
      terminal domains, each of which are required for activation of a classical AP-1
      reporter. Gel shift studies demonstrated that protein binding to the CYP11A1 EGF
      RE was competed specifically by a canonical AP-1 site, and the addition of an
      anti-JUN antibody confirmed the presence of AP-1 proteins. Consistent with the
      possibility that EGF may act in part via c-Jun, EGF stimulated the activity of a
      chimeric GAL4 c-Jun protein, indicating that JUN can serve as a potential target
      of EGF in JEG-3 cells. EGF also induced mitogen-activated protein kinase
      activity, and a dominant negative mutant of mitogen-activated protein kinase
      partially blocked EGF stimulation of GAL4 c-Jun activity. We conclude that EGF
      stimulates the CYP11A1 promoter through an AP-1 like element and that c-Jun is
      one of the targets of EGF action.

PMID- 7629151
TI  - Reaction mechanism of L-2-haloacid dehalogenase of Pseudomonas sp. YL.
      Identification of Asp10 as the active site nucleophile by 18O incorporation
      experiments.
AB  - L-2-Haloacid dehalogenase (EC 3.8.1.2) catalyzes the hydrolytic dehalogenation of
      L-2-haloacids to produce the corresponding D-2-hydroxy acids. We have analyzed
      the reaction mechanism of the enzyme from Pseudomonas sp. YL and found that Asp10
      is the active site nucleophile. When the multiple turnover enzyme reaction was
      carried out in H2(18)O with L-2-chloropropionate as a substrate, lactate produced
      was labeled with 18O. However, when the single turnover enzyme reaction was
      carried out by use of a large excess of the enzyme, the product was not labeled.
      This suggests that an oxygen atom of the solvent water is first incorporated into
      the enzyme and then transferred to the product. After the multiple turnover
      reaction in H2(18)O, the enzyme was digested with lysyl endopeptidase, and the
      molecular masses of the peptide fragments formed were measured by an ionspray
      mass spectrometer. Two 18O atoms were shown to be incorporated into a
      hexapeptide, Gly6-Lys11. Tandem mass spectrometric analysis of this peptide
      revealed that Asp10 was labeled with two 18O atoms. Our previous site-directed
      mutagenesis experiment showed that the replacement of Asp10 led to a significant
      loss in the enzyme activity. These results indicate that Asp10 acts as a
      nucleophile on the alpha-carbon of the substrate leading to the formation of an
      ester intermediate, which is hydrolyzed by nucleophilic attack of a water
      molecule on the carbonyl carbon atom.

PMID- 7629152
TI  - Heterologous expression and enzymatic properties of a selenium-independent
      glutathione peroxidase from the parasitic nematode Brugia pahangi.
AB  - A full-length cDNA from the parasitic nematode Brugia pahangi encoding a secreted
      homolog of glutathione peroxidase in which the codon for the active site
      selenocysteine is substituted naturally by a cysteine codon has been expressed in
      Spodoptera frugiperda (insect) cells via Autographa californica nuclear
      polyhedrosis virus (baculovirus). The recombinant protein was glycosylated and
      secreted from the cells in tetrameric form. The purified protein showed
      glutathione peroxidase activity with a range of organic hydroperoxides, including
      L-alpha-phosphatidylcholine hydroperoxide, but no significant activity against
      hydrogen peroxide. Glutathione was the only thiol tested that served as a
      substrate for the enzyme, which showed no activity with the thioredoxin system
      (thioredoxin, thioredoxin reductase, and NADPH). No glutathione-conjugating
      activity was detected against a range of electrophilic compounds that are common
      substrates for glutathione S-transferases. The apparent (pseudo)m for glutathione
      was determined as 4.9 mM at a fixed concentration of linolenic acid hydroperoxide
      (3 microM). The enzyme showed low affinity for hydroperoxide substrates (apparent
      Km for linolenic acid hydroperoxide and L-alpha-phosphatidylcholine hydroperoxide
      of 3.8 and 9.7 mM, respectively at a fixed glutathione concentration of 3 mM).

PMID- 7629153
TI  - Variants of tissue-type plasminogen activator which display substantially
      enhanced stimulation by fibrin.
AB  - Unlike most proteases, tissue-type plasminogen activator (t-PA) is secreted from
      cells as an active, single chain "proenzyme" whose catalytic efficiency is
      comparable with that of the corresponding mature, two-chain enzyme. We have
      previously suggested that the absence of the "zymogen triad" (Asp194-His40-Ser32;
      chymotrypsin numbering) contributes to this unusually high enzymatic activity of
      single chain t-PA. Consistent with this prediction, the single chain form of a
      variant of t-PA containing the zymogen triad displayed dramatically reduced
      activity toward synthetic substrates. Activation cleavage of this variant,
      however, resulted in a mature, two-chain enzyme with full catalytic activity. To
      further examine the functional significance of the zymogen triad, we used site
      specific mutagenesis to construct a variant of t-PA, t-PA/R275E,A292S,F305H, that
      contained this triad but could not be converted into its two-chain form by
      plasmin. Characterization of this variant demonstrated that the presence of the
      zymogen triad specifically suppressed plasminogen activation by single chain t-PA
      in the absence of fibrin. In addition, these studies indicated that, like wild
      type t-PA, zymogen activation of this variant could be accomplished by binding to
      the co-factor fibrin. The combination of full activity in the presence of fibrin
      and reduced activity in its absence resulted in novel variants of t-PA that
      displayed dramatically enhanced stimulation by fibrin. While the presence of
      fibrin increased the catalytic efficiency of t-PA toward plasminogen by a factor
      of approximately 520, this stimulation factor increased to 130,000 for t
      PA/R275E,A292S,F305H. Plasmin-resistant, zymogen-like variants of t-PA,
      therefore, may represent thrombolytic enzymes with enhanced "clot selectivity."

PMID- 7629154
TI  - Hsp47 and cyclophilin B traverse the endoplasmic reticulum with procollagen into
      pre-Golgi intermediate vesicles. A role for Hsp47 and cyclophilin B in the export
      of procollagen from the endoplasmic reticulum.
AB  - Hsp47 and cyclophilin B (CyPB) are residents of the endoplasmic reticulum (ER).
      Both of these proteins are closely associated with polysome-associated alpha 1(I)
      procollagen chains. Hsp47 possesses chaperone properties early during the
      translation of procollagen while the cis/trans-isomerase properties of CyPB
      facilitate procollagen folding. In this report, we further investigate the
      interaction of these proteins with procollagen I during export from the ER. To
      inhibit vesicular budding and retain procollagen within the ER, cells were
      treated with the heterotrimeric G protein inhibitor mastoparan or calphostin C, a
      specific inhibitor of diacylglycerol/phorbol ester binding proteins. To arrest
      procollagen in pre-Golgi intermediate vesicles, cells were treated with guanosine
      5'-3-O-(thio)triphosphate. Pulse-chase experiments of cells labeled with
      [35S]methionine followed by immunoprecipitation during the chase period with anti
      procollagen, anti-Hsp47, and anti-CyPB antibodies were performed to reveal the
      relationship between Hsp47/CyPB/procollagen I. The distribution of procollagen,
      Hsp47, and CyPB to the ER and/or pre-Golgi vesicles was verified by
      immunofluorescence. Hsp47 and CyPB remained associated with procollagen retained
      within the ER. Hsp47 and CyPB were also associated with procollagen exported from
      the ER into pre-Golgi intermediate vesicles. Treatment of cells with cyclosporin
      A diminished the levels of CyPB bound to procollagen and diminished the rate of
      Hsp47 released from procollagen and the rate of procollagen secretion, suggesting
      that Hsp47 release from procollagen may be driven by helix formation. Also, these
      studies suggest that Hsp47 may resemble protein disulfide isomerase and possess
      both chaperone and anti-chaperone properties. During translation, high levels of
      Hsp47 are seen to limit protein aggregation and facilitate chain registration.
      Later, Hsp47 and/or CyPB and protein disulfide isomerase act as anti-chaperones
      and provide the basis for concentration of procollagen for ER export.

PMID- 7629155
TI  - Effects of the antiterminator BoxA on transcription elongation kinetics and ppGpp
      inhibition of transcription elongation in Escherichia coli.
AB  - It has been shown previously that two different mRNA chains (lacZ and infB) are
      elongated at a rate of approximately 40 nucleotides (nt)/s during steady state
      growth on minimal medium and that the rate of mRNA chain elongation is inhibited
      by ppGpp in vivo. On the other hand, it was found that a truncated ribosomal RNA
      chain was elongated at a rate of approximately 80 nt/s, independent of growth
      condition (Vogel, U., and Jensen, K. F. (1994) J. Biol. Chem. 269, 16236-16241).
      We reasoned that the different transcriptional behavior of mRNA genes and rRNA
      operons might be caused by the antiterminator sequences present in the rRNA
      operons. To test this possibility, we have (a) inserted the minimal
      antiterminator boxA sequence between the promoter and the lacZ and infB genes and
      (b) deleted the antiterminator sequences from the rRNA transcription unit and
      measured transcription elongation rates in vivo on the resulting hybrid genes. We
      found that insertion of boxA in front of the coding region of lacZ increased the
      transcription elongation rate from 42 nt/s to 69 nt/s during steady state growth
      and that it eliminated the ppGpp-dependent decrease in the transcription
      elongation rate during the stringent response. On the other hand, deletion of the
      antiterminator sequences from the rRNA operon resulted in a reduced transcription
      elongation rate, but the elongation rate was still insensitive to changes in the
      ppGpp pool. These results are consistent with the hypothesis that the
      antiterminator boxA is a primary determinant of the rate of transcription
      elongation rate.

PMID- 7629156
TI  - Isolation and characterization of a cDNA encoding the SecA protein from spinach
      chloroplasts. Evidence for azide resistance of Sec-dependent protein
      translocation across thylakoid membranes in spinach.
AB  - Thylakoid membranes of chloroplasts in higher plants harbor different pathways
      for the translocation of proteins. One of these routes is related to the
      prokaryotic Sec pathway, which mediates the secretion of particular proteins into
      the periplasmic space and involves the SecA protein as an essential component. We
      have isolated a full size cDNA of 3739 nucleotides encoding the SecA homologue
      from spinach. It contains an open reading frame of 1036 codons corresponding to a
      polypeptide with a calculated mass of 117 kDa. The deduced amino acid sequence
      shows between 43 and 49% identity to SecA proteins from bacteria and lower algae
      and 62% identity to SecA of the cyanobacterium Synechococcus sp. PCC7942.
      Compared with the Escherichia coli protein, spinach SecA carries an amino
      terminal extension of approximately 80 residues. In organello experiments
      performed with the protein made in vitro by transcription of the cDNA and cell
      free translation of the resulting RNA showed that this extension comprises a
      transit peptide that mediates the import of the protein into the chloroplast. The
      processed product of approximately 107 kDa accumulates predominantly in the
      stroma and to a lower extent associates with the thylakoid membrane. Comparably
      to E. coli, in which SecA activity can be inhibited by sodium azide, thylakoid
      translocation of a subset of lumenal proteins is sensitive to sodium azide in pea
      but not in spinach chloroplasts, suggesting that the latter contain an azide
      resistant SecA variant.

PMID- 7629157
TI  - Activation of NF-kappa B by phosphatase inhibitors involves the phosphorylation
      of I kappa B alpha at phosphatase 2A-sensitive sites.
AB  - Activation of NF-kappa B by various cellular stimuli involves the phosphorylation
      and subsequent degradation of its inhibitor, I kappa B alpha, although the
      underlying mechanism remains unclear. In the present study, the role of
      serine/threonine phosphatases in the regulation of I kappa B alpha
      phosphorylation was investigated. Our studies demonstrate that incubation of
      human T cells with low concentrations (approximately 1-5 nM) of calyculin A or
      okadaic acid, potent inhibitors of protein phosphatase type 1 (PP-1) and type 2A
      (PP-2A), induces the phosphorylation of I kappa B alpha even in the absence of
      any cellular stimulus. This action of the phosphatase inhibitors, which is
      associated with the activation of the RelA.p50 NF-kappa B heterodimer, is not
      affected by agents that block the induction of I kappa B alpha phosphorylation by
      tumor necrosis factor alpha (TNF-alpha). Furthermore, the phosphorylated I kappa
      B alpha from calyculin A-treated cells, but not that from TNF-alpha-stimulated
      cells, is sensitive to PP-2A in vitro, suggesting the existence of fundamental
      differences in the phosphorylation of I kappa B alpha induced by the two
      different NF-kappa B inducers. However, induction of I kappa B alpha
      phosphorylation by both TNF-alpha and the phosphatase inhibitors is associated
      with the subsequent degradation of I kappa B alpha. We further demonstrate that
      TNF-alpha- and calyculin A-induced I kappa B alpha degradation exhibits similar
      but not identical sensitivities to a proteasome inhibitor. Together, these
      results suggest that phosphorylation of I kappa B alpha, mediated through both
      the TNF-alpha-inducible and the PP-2A-opposing kinases, may serve to target I
      kappa B alpha for proteasome-mediated degradation.

PMID- 7629158
TI  - Phosphorylation and activation of the ATP-Mg-dependent protein phosphatase by the
      mitogen-activated protein kinase.
AB  - Inhibitor-2 (I-2) is the regulatory subunit of the cytosolic ATP-Mg-dependent
      form of type 1 serine/threonine protein phosphatase and its phosphorylation at
      Thr-72 by glycogen synthase kinase-3 results in phosphatase activation.
      Activation of cytosolic type 1 phosphatase has been observed in cells treated
      with growth factors. Reported here is the phosphorylation and activation of the
      ATP-Mg-dependent phosphatase by mitogen-activated protein kinase (MAPK).
      Recombinant I-2 was phosphorylated by activated MAPK to an extent (approximately
      0.3 mol of phosphate/mol of polypeptide) similar to that reported for
      phosphorylation by the alpha isoform of glycogen synthase kinase-3. The
      phosphorylation of I-2 by MAPK was exclusively at Thr-72, the site involved in
      the activation of phosphatase. Incubation of MAPK with purified ATP-Mg-dependent
      phosphatase resulted in phosphorylation of the I-2 component and activation of
      the phosphatase. Ribosomal S6 protein kinase II (p90rsk) was also able to
      phosphorylate the recombinant I-2; however, this phosphorylation occurred on
      serines and had no effect on phosphatase activation. Our data may explain growth
      factor-induced activation of the ATP-Mg-dependent phosphatase and suggest that
      MAPK may of cytosolic type 1 phosphatase in response to insulin and/or other
      growth factors.

PMID- 7629159
TI  - Pharmacological and biochemical profiles of unique neurotensin 8-13 analogs
      exhibiting species selectivity, stereoselectivity, and superagonism.
AB  - Recently, the rat neurotensin receptor and the two human neurotensin receptor
      clones (differing by one amino acid residue) have been isolated. We present
      results with 33 newly synthesized neurotensin analogs. We have evaluated their
      binding potency at the three neurotensin receptor clones by determining
      equilibrium dissociation constants and coupling to phosphatidylinositol turnover.
      Our work focused on position 8 and 9 substitutions as well as position 11 of the
      neurotensin hexamer NT8-13. The results presented include: 1) the development of
      a compound that is species selective, with a binding potency at the rat receptor
      that is 20-fold more potent than at the human receptor; 2) the development of a
      pair of stereoselective compounds with the L-isomer exhibiting 190-700-fold more
      potency than the D-isomer; and 3) the development of an agonist that has a Kd of
      0.3 and 0.2 nM at the human and rat neurotensin receptor, respectively, ranking
      it as among the most potent tested. Also, we present the first evidence that 1)
      the effect of pi electrons at position 11 (L-Tyr) are important for binding to
      the neurotensin receptor, and 2) the length of the side chain on position 9 (L
      Arg) changes binding potency.

PMID- 7629160
TI  - Effects of tumor necrosis factor-alpha on antimitogenicity and cell cycle-related
      proteins in MCF-7 cells.
AB  - Tumor necrosis factor-alpha (TNF-alpha) demonstrated antimitogenic activity in
      MCF-7 cells (estrogen receptor-positive human breast cancer cells) in a dose- and
      time-dependent manner (EC-50 of 2.5 ng/ml). This antimitogenic effect of TNF
      alpha was accompanied by a decreased number of cells in S phase in a dose- and
      time-dependent manner. Based on growth arrest experiments using aphidicolin, it
      is apparent that TNF-alpha acted in early G1 phase. It did not show antimitogenic
      effects once cells reentered the S phase based on [3H]thymidine incorporation
      into DNA and cell cycle analysis. Specificity of TNF-alpha was established by
      using monoclonal anti-human TNF-alpha antibody. On the basis of Western
      immunoblot analysis of Rb, p53 and cell cycle inhibitory protein (Cip1) (p21)
      proteins, TNF-alpha decreased Rb protein expression in a dose- and time-dependent
      manner whereas it increased the expression level of tumor suppressor p53 protein.
      TNF-alpha also increased the expression level of Cip1 (p21) protein in a dose
      dependent manner. This induction of Cip1 (p21) protein was preceded by the
      induction of p53 protein in MCF-7 cells. Cip1 (p21) protein associated with
      cyclin D was also increased. Tumor suppressor Rb protein expression was increased
      during G1 to S phase progression. Cyclin D protein expression levels were not
      changed in response to TNF-alpha treatment, although serine/threonine kinase
      inhibitors such as H7 and the protein kinase C inhibitor staurosporine decreased
      cyclin D expression levels in MCF-7 cells. Based on experiments with
      staurosporine, it appears that TNF-alpha does not utilize a protein kinase C
      pathway in MCF-7 cells. Other cell cycle-related proteins such as Cdk2, Cdc2, and
      Cdk4 did not show any change in response to TNF-alpha. TNF-alpha did not affect
      complexes between cyclin D and Cdk2, Cdk4, and Rb proteins in MCF-7 cells. Taken
      together these results suggest that Rb, p53, and Cip1 (p21) proteins mediate TNF
      alpha antimitogenic activity, and TNF-alpha induces growth arrest in the G1 phase
      in MCF-7 cells.

PMID- 7629161
TI  - Singlet oxygen and peroxyl radicals regulate carotenoid biosynthesis in Phaffia
      rhodozyma.
AB  - Carotenoids have recently received considerable interest because of their
      potential in delaying or preventing degenerative diseases such as
      arteriosclerosis, cancer, and aging. In this study we show that the active oxygen
      species singlet oxygen (1O2) and peroxyl radicals differently affect carotenoid
      composition and biosynthesis in the yeast Phaffia rhodozyma. Photochemical
      generation of 1O2 with rose bengal or alpha-terthienyl induced carotenoid
      accumulation. In contrast, peroxyl radicals derived from t-butylhydroperoxide
      (tBOOH) or H2O2 decreased the content of astaxanthin and increased beta-carotene
      by approximately 4-fold, suggesting end product feedback regulation by
      astaxanthin or inhibition of biosynthetic enzymes. 14C labeling of carotenoids
      during oxidative stress supported the possibility of end product regulation.
      Carotenoids were bleached by 8 mM tBOOH within 6 h when carotenogenesis was
      inhibited by thymol. When treated with peroxides, a previously unreported pigment
      in P. rhodozyma was formed. The carotenoid had a mass of 580 Da and a molecular
      formula of C40H52O3. Chemical derivatizations combined with mass and absorbance
      spectroscopy tentatively identified the carotenoid as dehydroflexixanthin (3,1'
      dihydroxy-2,3,3',4'-tetradehydro-1',2'-dihydro-beta,psi-caro tene-4-one). This
      study provides the first report of induction of astaxanthin biosynthesis by 1O2,
      probable feedback control by astaxanthin, and the oxidative degradation of
      astaxanthin to novel pigments in P. rhodozyma.

PMID- 7629162
TI  - Alteration in the retinoid specificity of retinoic acid receptor-beta by site
      directed mutagenesis of Arg269 and Lys220.
AB  - Retinoic acid receptor-beta (RAR-beta) specifically binds retinoic acid (RA) and
      functions as a RA-inducible transcriptional regulatory factor. Simultaneous
      mutation of Arg269 and Lys220 of RAR-beta to Ala results in a dramatic reduction
      in both transactivation and affinity for RA along with creating a RA
      concentration-dependent dominant negative mutant. In this report, we found that
      mutation of these two amino acid residues singly and simultaneously to Gln
      results in mutant RAR-beta s, each displaying a more dramatic reduction in
      transactivation and affinity for RA than their corresponding Ala mutant, with the
      R269Q more profoundly affected than K220Q. Furthermore, we examined both the Ala
      and Gln mutants for their ability to transactivate and bind two other retinoids
      with different functional end groups (all-trans-retinol and all-trans-retinal).
      Mutation of Lys220 to either an Ala or a Gln favors transactivation and binding
      of retinal, while mutation of either Lys220 or Arg269 to Gln favors retinol
      transactivation and binding. Taken together, these results suggest that Arg269
      and Lys220 lie within the ligand binding pocket of RAR-beta and Lys220 lie within
      the ligand binding pocket of RAR-beta and that these two amino acid residues play
      an important role in determining retinoid specificity most likely by directly
      interacting with the carboxylate group of RA.

PMID- 7629164
TI  - Molecular cloning and nucleotide sequences of the genes for two essential
      proteins constituting a novel enzyme system for heptaprenyl diphosphate
      synthesis.
AB  - The genes encoding two dissociable components essential for Bacillus
      stearothermophilus heptaprenyl diphosphate synthase (all-trans-hexparenyl
      diphosphate:isopentenyl-diphosphate hexaprenyl-trans-transferase, EC 2.5.1.30)
      were cloned, and their nucleotide sequences were determined. Sequence analyses
      revealed the presence of three open reading frames within 2,350 base pairs,
      designated as ORF-1, ORF-2, and ORF-3 in order of nucleotide sequence, which
      encode proteins of 220, 234, and 323 amino acids, respectively. Deletion
      experiments have shown that expression of the enzymatic activity requires the
      presence of ORF-1 and ORF-3, but ORF-2 is not essential. As a result, this enzyme
      was proved genetically to consist of two different protein compounds with
      molecular masses of 25 kDa (Component I) and 36 kDa (Component II), encoded by
      two of the three tandem genes. The protein encoded by ORF-1 has no similarity to
      any protein so far registered. However, the protein encoded by ORF-3 shows a 32%
      similarity to the farnesyl diphosphate synthase of the same bacterium and has
      seven highly conserved regions that have been shown typical in prenyltransferases
      (Koyama, T., Obata, S., Osabe, M., Takeshita, A., Yokoyama, K., Uchida, M.,
      Nishino, T., and Ogura, K. (1993) J. Biochem. (Tokyo) 113, 355-363).

PMID- 7629163
TI  - Expression cloning of lfc, a novel oncogene with structural similarities to
      guanine nucleotide exchange factors and to the regulatory region of protein
      kinase C.
AB  - In order to identify cDNAs that can induce oncogenic transformation, a retroviral
      vector was used to transfer a library of cDNAs from the murine 32D hemopoietic
      cell line into NIH 3T3 fibroblasts. We have identified and recovered a provirus
      containing a 1.8-kilobase pair cDNA whose expression causes morphological
      transformation in NIH 3T3 cells. The transforming cDNA contains a complete open
      reading frame that encodes a protein (designated Lfc) with a region of sequence
      similarity to the product of the lbc oncogene. This region includes a domain that
      is characteristic of the CDC24 family of guanine nucleotide exchange factors in
      tandem with a pleckstrin homology (PH) domain. The Lfc protein is distinguished
      from Lbc by a 150-amino acid NH2-terminal extension that contains a cysteine- and
      histidine-rich domain similar to the diacylglycerol-binding site (zinc butterfly)
      found in protein kinase C. NH2- and COOH-terminal deletion analysis revealed that
      both the PH and putative guanine nucleotide exchange factor domains are required,
      but the zinc butterfly is dispensable, for transformation. Although the removal
      of the PH domain of the Lfc protein completely eliminated its ability to
      transform NIH 3T3 cells, replacement of this domain with an isoprenylation site
      restored all of its transforming activity. This suggests that a PH domain
      dependent recruitment of the Lfc protein to the cellular membrane is a necessary
      step for cellular transformation. The lfc gene is expressed in a broad range of
      tissues as well as in a variety of hemopoietic and non-hemopoietic cell lines.
      Lfc appears to be a new member of a growing family of proteins that are likely to
      act as activators of Ras-like proteins in a developmental or cell-lineage
      specific manner.

PMID- 7629165
TI  - Aspartate 698 within a novel cation binding motif in alpha 4 integrin is required
      for cell adhesion.
AB  - The interactions of alpha 4 beta 1 integrin with vascular cell adhesion molecule
      (VCAM) and fibronectin play important roles in many physiological and
      pathological processes. To understand the mechanism of alpha 4 beta 1 integrin
      mediated cell adhesion, we made mutant alpha 4 constructs. Three aspartic acid
      (Asp) residues in alpha 4, Asp-489, Asp-698, and Asp-811, were replaced with
      glutamic acids (Glu). The wild-type and mutant alpha 4 constructs were
      transfected into K562 cells, and stable transfectants with similar levels of
      alpha 4 surface expression were established. The Asp-->Glu substitutions did not
      affect alpha 4 beta 1 association or heterodimer formation as demonstrated by
      immunoprecipitation analysis. However, the glutamate substitutions at Asp-489 and
      Asp-698 severely impaired cell adhesion to VCAM and fibronectin, whereas the
      substitution at Asp-811 had no detectable effect on cell adhesion. In contrast to
      these results, isolated alpha 4 beta 1, containing the D489E or D698E
      substitution, was able to bind to VCAM, suggesting that these two residues are
      not critical for ligand recognition. In searching for a mechanism to explain
      inhibition of adhesion by Asp-489 and Asp-698 mutations, we found that the
      sequences flanking Asp-698 resemble the DxxxxxD-S-Sx divalent cation/ligand
      binding motif in beta integrins and the I-domains of alpha integrins. This
      suggests that Asp-698 in the alpha 4 integrin, which does not possess an I
      domain, may also be involved in cation binding and may be part of a sequence
      functionally similar to that found in the I-domains of other alpha integrins.

PMID- 7629166
TI  - Identification of YHR068w in Saccharomyces cerevisiae chromosome VIII as a gene
      for deoxyhypusine synthase. Expression and characterization of the enzyme.
AB  - Deoxyhypusine synthase catalyzes the formation of deoxyhypusine, the first step
      in hypusine biosynthesis. Amino acid sequences of five tryptic peptides from rat
      deoxyhypusine synthase were found to match partially the deduced amino acid
      sequence of the open reading frame of gene YHR068w of Saccharomyces cerevisiae
      chromosome VIII (AC:U00061). In order to determine whether the product of this
      gene corresponds to yeast deoxyhypusine synthase,a 1.17-kilobase pair cDNA with
      an identical nucleotide sequence to that of the YHR068w coding region was
      obtained from S. cerevisiae cDNA by polymerase chain reaction and was expressed
      in Escherichia coli B strain BL21 (DE3). The recombinant protein was found mostly
      in the E. coli cytosol fraction and comprised approximately 20% of the total
      soluble protein. The purified form of the expressed protein effectively catalyzed
      the formation of deoxyhypusine in yeast eIF-5A precursors as well as in human
      precursor and in those from Chinese hamster ovary cells. The molecular mass of
      the enzyme was estimated to be 172,000 +/- 4,300 Da by equilibrium
      centrifugation. The mass of its polypeptide subunit was determined to be
      approximately 43,000 Da, in close agreement with that calculated for the coding
      region of the YHRO68w gene. These findings show that this gene is a coding
      sequence for yeast deoxyhypusine synthase and that the product of this gene
      exists in a tetrameric form.

PMID- 7629167
TI  - Horseradish peroxidase Phe172-->Tyr mutant. Sequential formation of compound I
      with a porphyrin radical cation and a protein radical.
AB  - A gene coding for the F172Y mutant of horseradish peroxidase isozyme C (HRP) has
      been constructed and expressed in both Spodoptera frugiperda (SF-9) and
      Trichoplusia ni egg cell homogenate (HighFive) cells. Homology modeling with
      respect to three peroxidases for which crystal structures are available places
      Phe172 on the proximal side of the heme in the vicinity of porphyrin pyrrole ring
      C. The pH optimum and spectroscopic properties of the F172Y mutant are
      essentially identical to those of wild type HRP. Vmax values show that the mutant
      protein retains most of the guaiacol oxidizing activity. Stopped flow studies
      indicate that Compound I is formed with H2O2 at the same rate (kappa 1 = 1.6 x
      10(7) M-1 s-1) at both pH 6.0 and 8.0 as it is with the wild type enzyme. This
      Compound I species decays rapidly at a rate kappa 2 = 1.01 s-1, pH 7.0, to a
      second two-electron oxidized species that retains the ferryl (FeIV = O)
      absorption. EPR studies establish that a ferryl porphyrin radical cation is
      present in the initial Compound I, but electron transfer from the protein results
      in formation of a second Compound I species with an unpaired electron on the
      protein (presumably on Tyr172). The presence or absence of oxidizable amino acids
      adjacent to the heme is thus a key determinant of whether the second oxidation
      equivalent in Compound I is found as a porphyrin or protein radical cation.

PMID- 7629168
TI  - Ligation of the T-cell antigen receptor (TCR) induces association of hSos1, ZAP
      70, phospholipase C-gamma 1, and other phosphoproteins with Grb2 and the zeta
      chain of the TCR.
AB  - Signaling by the T-cell antigen receptor (TCR) involves both phospholipase C
      (PLC)-gamma 1 and p21ras activation. While failing to induce Shc/Grb2
      association, ligation of the TCR/CD3 receptor in Jurkat T-cells induced hSos1
      Grb2 complexes. In addition to hSos1, Grb2 participates in the formation of a
      tyrosine phosphoprotein complex that includes 145-, 95-, 70-, 54-, and 36-38-kDa
      proteins. p145 was identified as PLC-gamma 1 and p70 as the protein tyrosine
      kinase, ZAP-70. Although of the same molecular weight, p95 was not recognized by
      an anti-serum to p95 Vav. The SH2 domains of Grb2 and PLC-gamma 1 were required
      for the formation of this protein complex. In anti-CD3-treated cells, Grb2
      redistributed from the cytosol to a particulate cell compartment along with
      p36/p38, ZAP-70, and PLC-gamma 1. Part of the Grb2 complex associated with the
      particulate compartment could be extracted with Nonidet P-40, while the rest was
      Nonidet P-40 insoluble. In both the detergent-soluble and -insoluble fractions,
      Grb2 coimmunoprecipitated with the zeta-chain of the TCR. Taken together, these
      results indicate that anti-CD3 induces Grb2-hSos1-PLC-gamma 1-p36/p38-ZAP70
      complexes, which localize in the vicinity of TCR-zeta.

PMID- 7629169
TI  - Hydrolysis of picolinylprolines by prolidase. A general mechanism for the dual
      metal ion containing aminopeptidases.
AB  - The velocity of enzymic cleavage of 4-substituted picolinylprolines by swine
      kidney prolidase approaches that of physiological dipeptides, but depends
      substantially upon the nature of the pyridine-ring substituent. The pH dependence
      of kcat/Km for picolinylproline is sigmoidal, with optimum activity on the acidic
      limb and a delimiting enzymic pKa of 6.6, unlike glycylproline (bell-shaped pH
      profile, maximum at pH 7.7). Productive chelation to an active site metal ion by
      the N terminus of substrates is indicated, with a water molecule ligated to that
      hyper(Lewis)acidic center prior to substrate binding supplying the pKa of 6.6.
      The rate-governing catalytic step differs according to the 4-substituent on the
      picolinyl residue; productive binding is slow in the case of electron-withdrawing
      groups, but subsequent nucleophilic addition to the metal ion-activated scissile
      linkage becomes controlling with more basic pyridine rings. Rate constants yield
      a Bronsted-type correlation with substrate pKa, providing a gauge of active-site
      Lewis acidity. A mechanism is suggested involving the cooperative participation
      of two especially acidic metal ions positioned adjacently within the active site
      (situated as in an homologous and structurally characterized aminopeptidase),
      with both serving to stabilize a bridging carboxamide-hydrate intermediate.

PMID- 7629170
TI  - Alpha-lactalbumin induces bovine milk beta 1,4-galactosyltransferase to utilize
      UDP-GalNAc.
AB  - We now report that alpha-lactalbumin (alpha-LA) has a novel effect on bovine milk
      UDP-Gal:GlcNAc-beta 1,4-galactosyltransferase (beta 1,4-GT) and induces the
      enzyme to efficiently utilize UDP-GalNAc as a donor. In the presence of alpha-LA
      the enzyme transfers GalNAc to free GlcNAc to produce GalNAc beta 1-4GlcNAc at a
      rate 55% of that compared to the rate when UDP-Gal is the donor in the absence of
      alpha-LA. The stimulation by alpha-LA is dependent on the concentrations of alpha
      LA, acceptor, and sugar nucleotide. Interestingly, beta 1,4-GT is unable to
      transfer Gal-NAc to Glc with or without alpha-LA. alpha-LA also stimulates the
      transfer of GalNAc from UDP-GalNAc to various chitin oligomers, although the
      degree of stimulation decreases as the acceptor size increases. Thus, bovine milk
      beta 1,4-GT has an inherent ability to utilize two different sugar nucleotides
      and the sugar nucleotide preference is regulatable by alpha-LA.

PMID- 7629171
TI  - Hyaluronic acid synthesis operon (has) expression in group A streptococci.
AB  - The has operon is composed of three genes, hasA, hasB, and hasC that encode
      hyaluronate synthase, UDP-glucose dehydrogenase, and presumptively UDP-glucose
      pyrophosphorylase, respectively. Expression of the has operon was shown to be
      required for the synthesis of the hyaluronic acid capsule in group A
      streptococci. Previous studies indicated that some group A and group C
      streptococcal strains produce the hyaluronic acid capsule, while others do not.
      In addition, it was observed that encapsulated strains cultured in stationary
      phase of growth lose the hyaluronic acid capsule. Therefore, the molecular
      mechanisms controlling the expression of the hyaluronic acid capsule in group A
      streptococci was investigated. In this study, it was determined that all
      encapsulated and unencapsulated strains of group A streptococci as well as
      encapsulated group C streptococci analyzed possess the has operon locus. The
      acapsular phenotype was accounted for by the absence of hyaluronate synthase
      activity in the membrane and not the production of extracellular hyaluronidase. A
      has operon mRNA transcript was not expressed by unencapsulated strains of group A
      streptococci, whereas encapsulated strains of group A streptococci grown to mid
      to late exponential phase produced the hyaluronate capsule, as well as has operon
      mRNA. However, as the streptococci entered the stationary phase of growth, they
      became acapsular and this was concomitant with the loss of has operon mRNA
      transcript. These results were confirmed by primer extension analyses of RNA
      isolated from encapsulated and unencapsulated strains of group A streptococci as
      well as RNA prepared from encapsulated strains cultured in exponential and
      stationary phases of growth. Thus, the loss of has operon mRNA in unencapsulated
      group A streptococci, as well as growth phase regulation occurs at the previously
      mapped has operon promoter. These data suggested that the synthesis of the
      hyaluronic acid capsule for group A streptococci may be controlled by
      transcriptional mechanisms.

PMID- 7629172
TI  - Phosphorylation of dihydropyridine receptor II-III loop peptide regulates
      skeletal muscle calcium release channel function. Evidence for an essential role
      of the beta-OH group of Ser687.
AB  - In vertebrate skeletal muscle, excitation-contraction coupling may occur by a
      mechanical coupling mechanism involving protein-protein interactions between the
      dihydropyridine receptor (DHPR) of the transverse tubule membrane and the
      ryanodine receptor (RYR)/Ca2+ release channel of the sarcoplasmic reticulum
      membrane. We have previously shown that the cytoplasmic II-III loop peptides of
      the skeletal and cardiac muscle DHPR alpha 1 subunits (SDCL and CDCL,
      respectively) activate the skeletal muscle RYR. We now report that cyclic AMP
      dependent protein kinase-mediated phosphorylation of Ser687 of SDCL yields a
      peptide that fails to activate the RYR, as determined in [3H]ryanodine binding
      and single channel measurements. The phosphorylated SDCL bound to the skeletal
      muscle but not cardiac muscle RYR, and the binding could be displaced by the
      unphosphorylated SDCL. A mutant SDCL with a Ser687-->Ala substitution failed to
      activate the RYR, but was still able to bind. Similarly, a Ser813-->Ala
      substitution in CDCL yielded a peptide that failed to activate the skeletal RYR.
      Use of three smaller overlapping peptides within the SDCL region identified an
      amino acid region from 666 to 726 including Ser687, which bound to and activated
      the skeletal muscle RYR. These results suggest that cyclic AMP-dependent protein
      kinase-mediated phosphorylation of the DHPR alpha 1 subunit may play a role in
      the functional interaction of the DHPR and RYR in skeletal muscle.

PMID- 7629173
TI  - Identification of dantrolene binding sites in porcine skeletal muscle
      sarcoplasmic reticulum.
AB  - Dantrolene, an intracellularly acting skeletal muscle relaxant, inhibits Ca2+
      release from the sarcoplasmic reticulum during excitation-contraction coupling by
      an unknown mechanism. The drug is used to treat malignant hyperthermia, a genetic
      sensitivity to volatile anesthetics which results in the massive release of
      intracellular Ca2+ from affected skeletal muscle. We hypothesize that
      determination of the site of action of dantrolene will lead to further
      understanding of the regulation of sarcoplasmic reticulum calcium release. We
      report the identification of specific dantrolene binding sites in porcine
      skeletal muscle sarcoplasmic reticulum using a rapid filtration binding assay for
      [3H]dantrolene. The binding isotherm in the heavy sarcoplasmic reticulum fraction
      indicates a single binding site with a Kd of 277 +/- 25 nM and a Bmax of 13.1 +/-
      1.5 pmol/mg of protein. Pharmacological specificity is characterized by
      inhibition of [3H]dantrolene binding with unlabeled dantrolene, or azumolene, a
      physiologically active congener, but not with aminodantrolene, which is
      physiologically inactive. Drug binding is maximal at pH 6.5-7.5, requires no Ca2+
      or Mg2+, and is inhibited by salt concentrations above 100 mM. [3H]Dantrolene
      binding is greatest in the sarcoplasmic reticulum, which contains the ryanodine
      receptor, the primary calcium release channel. No binding is detected in the
      fractions enriched for sarcolemma or transverse tubules. We suggest that
      dantrolene inhibits calcium release from the sarcoplasmic reticulum by either
      direct or indirect interaction with the ryanodine receptor.

PMID- 7629174
TI  - Generation and biological characterization of membrane-bound, uncleavable murine
      tumor necrosis factor.
AB  - Tumor necrosis factor (TNF) is produced as a membrane-bound, 26-kDa proform from
      which the mature, 17-kDa TNF subunit is released by proteolytic cleavage. In
      order to compare the biological activity of membrane-bound versus soluble TNF,
      mutational analysis of potential cleavage sites in murine TNF was carried out.
      The biological activity was assessed after transfection in L929 cells. Deletion
      of the first nine codons of the mature part of the murine TNF gene still led to
      the production of secretable TNF, indicating alternative cleavage sites separate
      from the -1/+1 junction. However, an additional deletion of 3 amino acids,
      generating TNF delta 1-12, resulted in a membrane-bound form of TNF. Site
      directed mutagenesis revealed Lys11 as the critical residue for alternative
      cleavage. Mutation of this residue to Glu in a TNF delta 1-9 mutant gave rise to
      uncleavable, membrane-bound TNF with biological activities similar to wild-type
      TNF. Induction of apoptosis, proliferation, or cytokine production by triggering
      of either 55-kDa or 75-kDa TNF receptors in appropriate cell lines occurred
      efficiently both with soluble and with membrane-bound TNF. The latter was,
      however, less active in the cytotoxic assays on U937 cells in which the 75-kDa
      TNF receptor is not signaling, but contributes to maximal TNF activity by ligand
      passing. This indicates that membrane-bound TNF cannot be passed from the 75-kDa
      to the 55-kDa TNF receptor.

PMID- 7629175
TI  - Coordinated regulation of and transcriptional activation by Xenopus thyroid
      hormone and retinoid X receptors.
AB  - Thyroid hormone (T3) plays a causative role in amphibian metamorphosis. This
      regulation is thought to be mediated by heterodimers of T3 receptors (TRs) and
      retinoid X receptors (RXRs). We report here that Xenopus TRs can indeed form
      strong heterodimers with Xenopus RXRs on the T3 response element (TRE) present in
      Xenopus TR beta genes. Using a T3-responsive in vivo transcription system
      established by introducing TRs and RXRs into Xenopus oocytes, we demonstrated
      that TR-RXR heterodimers repressed TR beta gene promoter in the absence of T3 and
      activated the promoter in the presence of the hormone. Furthermore, by analyzing
      the expression of TR and RXR genes, we showed that TR and RXR genes were
      coordinately regulated in different tissues during metamorphosis. Thus high
      levels of their mRNAs are present in the limb during early stages of limb
      development when morphogenesis occurs and in the tail toward the end of
      metamorphosis when it is being resorbed. Such correlations coupled with our TRE
      binding and in vivo transcriptional activation experiments provide strong
      evidence that TRs and RXRs function together to mediate the effects of T3 during
      metamorphosis. These results further suggest a possible molecular basis for the
      temporal regulation of tissue-specific metamorphosis.

PMID- 7629176
TI  - Structural and functional roles of cysteine 90 and cysteine 240 in S
      adenosylmethionine synthetase.
AB  - Site-specific mutagenesis was performed on the structural gene for Escherichia
      coli S-adenosylmethionine (AdoMet) synthetase to introduce mutations at cysteines
      90 and 240, residues previously implicated by chemical modification studies to be
      catalytically and/or structurally important. The AdoMet synthetase mutants (i.e.
      MetK/C90A, MetK/C90S, and MetK/C240A) retained up to approximately 10% of wild
      type activity, demonstrating that neither sulfhydryl is required for catalytic
      activity. Mutations at Cys-90 produced a mixture of noninterconverting dimeric
      and tetrameric proteins, suggesting a structural significance for Cys-90. Dimeric
      Cys-90 mutants retained approximately 1% of wild type activity, indicating a
      structural influence on enzyme activity. Both dimeric and tetrameric MetK/C90A
      had up to a approximately 70-fold increase in Km for ATP, while both dimeric and
      tetrameric MetK/C90S had Km values for ATP similar to the wild type enzyme,
      suggesting a linkage between Cys-90 and the ATP binding site. MetK/C240A was
      isolated solely as a tetramer and differed from wild type enzyme only in its 10
      fold reduction in specific activity, suggesting that the mutation affects the
      rate-limiting step of the reaction, which for the wild type enzyme is the joining
      of ATP and L-methionine to yield AdoMet and tripolyphosphate. Remarkably all of
      the mutants are much more thermally stable than the wild type enzyme.

PMID- 7629178
TI  - Phosphatidylethanolamine induces high affinity binding sites for factor VIII on
      membranes containing phosphatidyl-L-serine.
AB  - Synthetic membranes of phosphatidylcholine require inclusion of at least 5%
      phosphatidylserine (Ptd-L-Ser) to form binding sites for factor VIII. The
      relatively high requirement for Ptd-L-Ser suggests that stimulated platelets may
      contain another membrane constituent that enhances expression of factor VIII
      binding sites. We report that phosphatidylethanolamine (PE), which is exposed in
      concert with Ptd-L-Ser in the course of platelet stimulation, induces high
      affinity binding sites for factor VIII on synthetic membranes containing 1-15%
      Ptd-L-Ser. The affinity of factor VIII for binding sites on membranes of Ptd-L
      Ser/PE/phosphatidylcholine in a 4:20:76 ratio was 10.2 +/- 3.5 nM with 180 +/- 33
      phospholipid molecules/site. PE did not induce binding sites on membranes of 4%
      Ptd-D-Ser, indicating that the induced binding sites require the correct
      stereochemistry of Ptd-L-Ser as well as PE. Egg PE and dimyristoyl-PE were
      equivalent for inducing factor VIII-binding sites, indicating that hexagonal
      phase-inducing properties of PE are not important. We conclude that PE induces
      high affinity factor VIII-binding sites on membranes with physiologic mole
      fractions of Ptd-L-Ser, possibly including those of stimulated platelets.

PMID- 7629177
TI  - Cloning and characterization of a Saccharomyces cerevisiae gene encoding the low
      molecular weight protein-tyrosine phosphatase.
AB  - The low molecular weight protein-tyrosine phosphatase (low M(r) PTPase) is an 18
      kDa cytoplasmic enzyme of unknown function that has been previously found in
      several vertebrates. Using an oligonucleotide probe derived from the active site
      sequence of the mammalian low M(r) PTPases, a Saccharomyces cerevisiae gene that
      encodes a homolog of this enzyme was cloned by low stringency hybridization. This
      gene, LTP1, together with a neighboring gene, TKL1, is shown to be located on the
      right arm of chromosome XVI. The deduced amino acid sequence of its 161-amino
      acid residue product shows a 39% average identity with that of the mammalian
      enzymes. The yeast Ltp1 protein was expressed in Escherichia coli, purified to
      homogeneity, and shown to possess PTPase activity. The recombinant Ltp1
      efficiently hydrolyzes phosphotyrosine and a phosphotyrosine-containing peptide,
      Tyr531-fyn, but it shows low activity toward phosphoserine and phosphothreonine.
      The catalytic activity of Ltp1 toward a number of substrates was approximately 30
      fold lower than the corresponding values measured for the bovine low M(r) PTPase.
      However, the yeast enzyme was markedly activated by adenine and some purine
      nucleosides and nucleotides, including cAMP and cGMP. In the case of adenine, the
      activity of Ltp1 was increased by approximately 30-fold. The high degree of
      evolutionary conservation of the low M(r) PTPases implies a significant role for
      this enzyme. However, neither the disruption of the LTP1 gene nor an
      approximately 10-fold overexpression of its product in S. cerevisiae caused any
      apparent phenotypic changes under the conditions tested. No proteins related to
      Ltp1 could be detected in extracts of the ltp1 null mutant, either by
      immunoblotting or by gel-filtration analysis accompanied by extended kinetic
      assays, consistent with the conclusion that LTP1 is the only low M(r) PTPase
      encoding gene in S. cerevisiae.

PMID- 7629179
TI  - Steps involved in activation of the pro-matrix metalloproteinase 9 (progelatinase
      B)-tissue inhibitor of metalloproteinases-1 complex by 4-aminophenylmercuric
      acetate and proteinases.
AB  - The precursor of matrix metalloproteinase 9 (pro-MMP-9, progelatinase B)
      noncovalently binds to tissue inhibitor of metalloproteinases (TIMP)-1 through
      the C-terminal domain of each molecule. We have isolated the proMMP-9.TIMP-1
      complex from the medium of human fibrosarcoma HT-1080 cells and investigated the
      activation processes of the complex by 4-aminophenylmercuric acetate, trypsin,
      and matrix metalloproteinase 3 (MMP-3, stromelysin 1). The treatment of the
      proMMP-9.TIMP-1 complex with 4-aminophenylmercuric acetate or trypsin converts
      proMMP-9 to lower molecular weight species corresponding to active forms, but no
      gelatinolytic activity is detected. The lack of enzymic activity results from
      binding of TIMP-1 to the activated MMP-9. The treatment of the proMMP-9.TIMP-1
      complex with a possible physiological proMMP-9 activator, MMP-3, does not reveal
      any gelatinolytic activity unless the molar ratio of MMP-3 to the complex exceeds
      1. This is due to the inhibition of MMP-3 by TIMP-1 forming a ternary proMMP
      9.TIMP-1.MMP-3 complex. The formation of the ternary complex weakens the
      interaction between proMMP-9 and TIMP-1, resulting in partial dissociation of the
      complex into proMMP-9 and the TIMP-1.MMP-3 complex. When MMP-3 is in excess, the
      propeptide is completely processed, and the full activity of MMP-9 is detected.
      Similarly, the proMMP-9.TIMP-1 complex inhibits MMP-1 (interstitial collagenase)
      and in turn renders the proMMP-9 activable by a catalytic amount of MMP-3. These
      results suggest that formation of the proMMP-9.TIMP-1 complex regulates
      extracellular matrix breakdown in tissue by switching the predominant MMP
      activity from one type to another.

PMID- 7629180
TI  - An abundant, trans-spliced mRNA from Toxocara canis infective larvae encodes a 26
      kDa protein with homology to phosphatidylethanolamine-binding proteins.
AB  - A full-length mRNA encoding a secreted 26-kDa antigen of infective larvae of the
      ascarid nematode parasite Toxocara canis has been identified. This was
      characterized as a 1,082-base pair clone highly abundant (0.8-1.9%) in cDNA
      prepared from infective stage larvae but absent from cDNA from adult male worms.
      Sequence analysis revealed an open reading frame corresponding to a hydrophilic
      263-amino acid residue polypeptide with a 20-residue N-terminal signal peptide,
      indicating that it is secreted. The 5' end of the cDNA was isolated by polymerase
      chain reaction using a primer containing the nematode-spliced leader sequence,
      SL1, showing that the mRNA is trans-spliced. The molecular mass of the putative
      protein with the signal peptide removed is 26.01 kDa, and antibody to the
      recombinant protein expressed in bacterial vectors reacts with a similarly sized
      protein in T. canis excretory/secretory (TES) products. An identical sequence was
      obtained from a genomic clone isolated by expression screening with mouse
      antibody to TES. The 72 amino acid residues adjacent to the signal peptide form
      two homologous 36-residue motifs containing 6 cysteine residues; this motif is
      found also in the T. canis-secreted glycoprotein TES-120 and in genes of
      Caenorhabditis elegans. Sequence data base searches revealed significant
      similarity to 7 other sequences in a newly recognized gene family of
      phosphatidylethanolamine-binding proteins that includes yeast, Drosophila, rat,
      bovine, simian, and human genes and a representative from the filarial nematode
      Onchocerca volvulus. Assays with the T. canis recombinant 26-kDa protein
      expressed as a fusion with maltose-binding protein have confirmed
      phosphatidylethanolamine-binding specificity for this novel product.

PMID- 7629181
TI  - Purification and biochemical characterization of neuropeptide Y2 receptor.
AB  - Neuropeptide Y (NPY) receptors consist of three subtypes, designated NPY1, NPY2,
      and NPY3. The Y1 receptor has been cloned. The present study reports the
      purification of the NPY-Y2 receptor from porcine brain and its biochemical
      characterization. NPY receptors were solubilized and purified by sequential
      hydrophobic interaction, ion exchange, and NPY-affinity chromatography. By use of
      SDS-polyacrylamide gel electrophoresis, high performance liquid chromatography
      gel permeation chromatography, and chemical cross-linking studies, the affinity
      purified brain NPY-Y2 receptor was identified as a monomeric glycoprotein with a
      molecular mass of 60 kDa. Following deglycosylation, the molecular mass of the Y2
      receptor was decreased to 45 kDa. Although the 125I-NPY binding to the purified
      NPY receptor was considerably decreased by N-ethylmaleimide, guanine nucleotides
      had no effect. Therefore, the purified NPY-Y2 receptor is probably not associated
      with G-proteins, but may have intramolecular-free sulfhydryl groups. The specific
      activity of the isolated NPY-Y2 receptor is 15.8 nmol/mg of protein. The isolated
      receptor retained its capacity to bind to 125I-NPY, specific to NPY and peptide
      YY, and showed no cross-reactivity with any other peptides. Highly purified
      (10(9)-fold purification) NPY receptor from the brain was identified as the Y2
      subtype as demonstrated by its affinity to C-terminal fragments of NPY, including
      NPY-(13-36).

PMID- 7629182
TI  - Control of PHAS-I by insulin in 3T3-L1 adipocytes. Synthesis, degradation, and
      phosphorylation by a rapamycin-sensitive and mitogen-activated protein kinase
      independent pathway.
AB  - PHAS-I levels increased 8-fold as 3T3-L1 fibroblasts differentiated into
      adipocytes and acquired sensitivity to insulin. Insulin increased PHAS-I protein
      (3.3-fold after 2 days), the rate of PHAS-I synthesis (3-fold after 1 h), and the
      half-life of the protein (from 1.5 to 2.5 days). Insulin also increased the
      phosphorylation of PHAS-I and promoted dissociation of the PHAS-I eukaryotic
      initiation factor-4E (eIF-4E) complex, effects that were maximal within 10 min.
      With recombinant [H6]PHAS-I as substrate, mitogen-activated protein (MAP) kinase
      was the only insulin-stimulated PHAS-I kinase detected after fractionation of
      extracts by Mono Q chromatography; however, MAP kinase did not readily
      phosphorylate [H6]PHAS-I when the [H6]PHAS-I.eIF-4E complex was the substrate.
      Thus, while MAP kinase may phosphorylate free PHAS-I, it is not sufficient to
      dissociate the complex. Moreover, rapamycin attenuated the stimulation of PHAS-I
      phosphorylation by insulin and markedly inhibited dissociation of PHAS-I.eIF-4E,
      without decreasing MAP kinase activity. Rapamycin abolished the effects of
      insulin on increasing phosphorylation of ribosomal protein S6 and on activating
      p70S6K. The MAP kinase kinase inhibitor, PD 098059, markedly decreased MAP kinase
      activation by insulin, but it did not change PHAS-I phosphorylation or the
      association of PHAS-I with eIF-4E. In summary, insulin increases the expression
      of PHAS-I and promotes phosphorylation of multiple sites in the protein via
      multiple transduction pathways, one of which is rapamycin-sensitive and
      independent of MAP kinase. Rapamycin may inhibit translation initiation by
      increasing PHAS-I binding to eIF-4E.

PMID- 7629183
TI  - Specific Alu binding protein from human sperm chromatin prevents DNA methylation.
AB  - A protein from human sperm nuclei that specifically binds to Alu DNA repeats has
      been purified. The specific DNA binding site of this protein within the Alu
      sequence has been mapped by methylation interference and electrophoretic mobility
      shift assays. This sperm Alu binding protein selectively protects Alu elements
      from methylation in vitro and may be responsible for the unmethylated state of
      Alu sequences in the male germ line resulting in a parent-specific differential
      inheritance of Alu methylation.

PMID- 7629184
TI  - Mammalian DNA (cytosine-5-)-methyltransferase expressed in Escherichia coli,
      purified and characterized.
AB  - Besides modulating specific DNA-protein interactions, methylated cytosine,
      frequently referred to as the fifth base of the genome, also influences DNA
      structure, recombination, transposition, repair, transcription, imprinting, and
      mutagenesis. DNA (cytosine-5-)-methyltransferase catalyzes cytosine methylation
      in eukaryotes. We have cloned and expressed this enzyme in Escherichia coli,
      purified it to apparent homogeneity, characterized its properties, and we have
      shown that it hemimethylates DNA. The cDNA for murine maintenance
      methyltransferase was reconstructed and cloned for direct expression in native
      form. Immunoblotting revealed a unique protein (M(r) = 190,000) not present in
      control cells. The mostly soluble overexpressed protein was purified by DEAE,
      Sephadex, and DNA cellulose chromatography. Peak methylating activity correlated
      with methyltransferase immunoblots. The purified enzyme preferentially
      transferred radioactive methyl moieties to hemimethylated DNA in assays and on
      autoradiograms. All of the examined properties of the purified recombinant DNA
      methyltransferase are consistent with the enzyme purified from mammalian cells.
      Further characterization revealed enhanced in vitro methylation of premethylated
      oligodeoxynucleotides. The cloning of hemimethyltransferase in E. coli should
      allow facilitated structure-function mutational analysis of this enzyme, studies
      of its biological effects in prokaryotes, and potential large scale
      methyltransferase production for crystallography, and it may have broad
      applications in maintaining the native methylated state of cloned DNA.

PMID- 7629185
TI  - Role of Tyr residues in the contact region of anti-lysozyme monoclonal antibody
      HyHEL10 for antigen binding.
AB  - It has been shown that Tyr residues are unusually localized in the regions of
      antibodies responsible for contact with antigens (Padlan, E. A. (1990) Proteins
      Struct. Funct. Genet. 7, 112-124). In order to clarify the role of these Tyr
      residues in antigen binding, the interaction between hen egg white lysozyme (HEL)
      and its monoclonal antibody HyHEL10, whose structure has been well studied in
      complex with its antigen, was investigated. Four Tyr residues in the VH chain
      (HTyr-33, HTyr-50, HTyr-53, and HTyr-58) were replaced with Ala, Leu, Phe, or
      Trp, and the interactions between these mutant Fv fragments and HEL were studied
      by inhibition assay of the enzymatic activity of HEL and isothermal titration
      calorimetry. Twelve mutant Fv fragments could be expressed, but two mutants
      (HY50W and HY58W) could not be obtained in the Escherichia coli expression
      system, and a further two mutants (HY33A and HY50A) could not be purified by
      affinity chromatography. It was shown by inhibition assay that Tyr residues at
      each mutated site made positive contributions to the interaction to different
      degrees. Thermodynamic studies showed that the role of Tyr residues in antigen
      binding was to obtain enthalpic energy. The roles of Tyr residues in antibody
      HyHEL10 for the association with antigen, HEL, can be summarized as follows: 1)
      formation of hydrogen bonds by the hydroxyl group, 2), creating more favorable
      interactions through the aromatic ring and decreasing the entropic loss upon
      binding, and 3) allowing hydrophobic interaction through the side chain. The four
      Tyr residues studied here were found to play significant roles in the association
      in various ways.

PMID- 7629186
TI  - Heparin binding by fibronectin module III-13 involves six discontinuous basic
      residues brought together to form a cationic cradle.
AB  - The thirteenth type III domain of fibronectin binds heparin almost as well as
      fibronectin itself and contains a so-called heparin-binding consensus sequence,
      Arg6-Arg7-Ala8-Arg9 (residues 1697-1700 in plasma fibronectin). Barkalow and
      Schwarzbauer (Barkalow, F.J., and Schwarzbauer, J.E. (1991) J. Biol. Chem. 266,
      7812-7818) showed that mutation of Arg6-Arg7 in domain III-13 of recombinant
      truncated fibronectins abolished their ability to bind heparin-Sepharose.
      However, synthetic peptides containing this sequence have negligible affinity for
      heparin (Ingham, K.C., Brew, S.A., Migliorini, M. M., and Busby, T.F. (1993)
      Biochemistry 32, 12548-12553). We generated a three-dimensional model of
      fibronectin type III-13 based on the structure of a homologous domain from
      tenascin. The model places Arg23, Lys25, and Arg54 parallel to and in close
      proximity to the Arg6-Arg7-Ala8-Arg9 motif, suggesting that these residues may
      also contribute to the heparin-binding site. Domain III-13 and six single-site
      mutants containing Ser in place of each of the above-mentioned basic residues
      were expressed in Escherichia coli. All of the purified mutant domains melted
      reversibly with a Tm near that of the wild type indicating that they were
      correctly folded. When fluorescein-labeled heparin was titrated at physiological
      ionic strength, the wild type domain increased the anisotropy in a hyperbolic
      fashion with a Kd of 5-7 microM, close to that of the natural domain obtained by
      proteolysis of fibronectin. The R54S mutant bound 3-fold weaker and the remaining
      mutants bound at least 10-fold weaker than wild type. The results point out that
      the Arg6-Arg7-Ala8-Arg9 consensus sequence by itself has little affinity for
      heparin under physiological conditions, even when presented in the context of a
      folded domain. Thus, the heparin-binding site in fibronectin is more complex than
      previously realized. It is formed by a cluster of 6 positively charged residues
      that are remote in the sequence but brought together on one side of domain III-13
      to form a "cationic cradle" into which the anionic heparin molecule could fit.

PMID- 7629188
TI  - Selenocysteylation in eukaryotes necessitates the uniquely long aminoacyl
      acceptor stem of selenocysteine tRNA(Sec).
AB  - Selenocysteine synthesis is achieved on a specific tRNA, tRNA(Sec), which is
      first charged with serine to yield seryl-tRNA(Sec). Eukaryotic tRNA(Sec) exhibits
      an aminoacyl acceptor stem with a unique length of 9 base pairs. Within this
      stem, two base pairs, G5a.U67b and U6.U67, drew our attention, whose non-Watson
      Crick status is maintained in the course of evolution either through U6.U67 base
      conservation or base covariation at G5a.U67b. Single or double point mutations
      were performed, which modified the identity of either or both of the base pairs.
      Serylation by seryl-tRNA synthetase was unaffected by substitutions at either
      G5a.U67b or U6.U67. Instead, and quite surprisingly, changing G5a.U67b and U6.U67
      to G5a-C67b/U6.G67 or G5a-C67b/C6-G67 gave rise to a tRNA(Sec) mutant exhibiting
      a gain of function in serylation. This finding sheds light on the negative
      influence born by a few base pairs in the acceptor stem of tRNA(Sec) on its
      serylation abilities. The tRNA(Sec) capacities to support selenocysteylation were
      next examined with regard to a possible role played by the two non-Watson-Crick
      base pairs and the unique length of the acceptor stem. It first emerges from our
      study that tRNA(Sec) transcribed in vitro is able to support selenocysteylation.
      Second, none of the point mutations engineered at G5a.U67b and/or U6.U67
      significantly modified the selenocysteylation level. In contrast, reduction of
      the acceptor stem length to 8 base pairs led tRNA(Sec) to lose its ability to
      efficiently support selenocysteylation. Thus, our study provides strong evidence
      that the length of the acceptor stem is of prime importance for the serine to
      selenocysteine conversion step.

PMID- 7629187
TI  - Mechanism of activation of human neutrophil gelatinase B. Discriminating between
      the role of Ca2+ in activation and catalysis.
AB  - Gelatinase B is a Zn(2+)- and Ca(2+)-dependent endopeptidase that is secreted
      from cells as an inactive proenzyme. The enzyme can be activated in vitro by
      organomercurial compounds and by trypsin. The role of Ca2+ in autoproteolytic
      processing initiated by 4-aminophenylmercuric acetate and trypsin and in
      catalytic activity of the activated enzyme was investigated by zymography and by
      kinetic analysis. Treatment of unglycosylated 57.5-kDa pro-gelatinase B with 4
      aminophenylmercuric acetate (1 mM) in the absence of Ca2+ generated a 49-kDa
      inactive intermediate (E'), whereas a 41.5-kDa active species (E") was generated
      in the presence of Ca2+ (5 mM). Upon addition of Ca2+ to the reaction mixture of
      Ca(2+)-depleted E' or E" at 37 degrees C, E' showed a lag period in generation of
      the product as a function of time, but E" presented an immediate activity. The
      appearance of enzymatic activity of E' correlated with the generation of the E"
      species. NH2-terminal sequence analyses showed that E' and E" had the same NH2
      termini, i.e. Met-75, suggesting that Ca(2+)-dependent removal of COOH terminus
      of E' is required for activation of the enzyme. Treatment of pro-gelatinase B
      with trypsin in the absence of Ca2+, led to degradation of the enzyme. In the
      presence of Ca2+, trypsin processed the pro-enzyme to a 40-kDa active species. In
      contrast to E", this active species did not require Ca2+ for activity. The Ca2+
      dependence of E" activity was also abolished by treatment of the enzyme with
      trypsin. NH2-terminal sequence analysis indicated that amino acid residues 75-87
      had been removed from the NH2 terminus of E" by trypsin, suggesting that these
      residues are responsible for the Ca(2+)-dependent activity of the enzyme. Removal
      of Ca2+ and catalytic Zn2+ inhibited the activities of both E" and trypsin
      treated E". In the absence of Ca2+, either Zn2+, Co2+, Mn2+, or Cd2+ was able to
      restore the activity of trypsin-treated E". None of the divalent cations tested
      however, was able to stimulate the activity of E" in the absence of Ca2+. These
      experiments further suggest that binding of Ca2+ to E" or removal of the NH2
      terminal residues of the enzyme by trypsin induces a conformational change in the
      protein and makes the active site of the enzyme accessible to various metal ions
      rendering the enzyme active.

PMID- 7629189
TI  - Molecular cloning and expression of chick chondrocyte chondroitin 6
      sulfotransferase.
AB  - Chondroitin 6-sulfotransferase (C6ST) catalyzes the transfer of sulfate from 3'
      phosphoadenosine 5'-phosphosulfate to position 6 of the N-acetylgalactosamine
      residue of chondroitin. The enzyme has been purified previously to apparent
      homogeneity from the serum-free culture medium of chick chondrocytes. The
      purified enzyme also catalyzed the sulfation of keratan sulfate. We have now
      cloned the cDNA of the enzyme. This cDNA contains a single open reading frame
      that predicts a protein composed of 458 amino acid residues. The protein predicts
      a Type II transmembrane topology similar to other glycosyltransferases and
      heparin/heparan sulfate N-sulfotransferase/N-deacetylases. Evidence that the
      predicted protein corresponds to the previously purified C6ST was the following:
      (a) the predicted sequence of the protein contains all of the known amino acid
      sequence, (b) when the cDNA was introduced in a eukaryotic expression vector and
      transfected in COS-7 cells, both the C6ST activity and the keratan sulfate
      sulfotransferase activity were overexpressed, (c) a polyclonal antibody raised
      against a fusion peptide, which was expressed from a cDNA containing the sequence
      coding for 150 amino acid residues of the predicted protein, cross-reacted to the
      purified C6ST, and (d) the predicted protein contained six potential sites for N
      glycosylation, which corresponds to the observation that the purified C6ST is an
      N-linked glycoprotein. The amino-terminal amino acid sequence of the purified
      protein was found in the transmembrane domain, suggesting that the purified
      protein might be released from the chondrocytes after proteolytic cleavage in the
      transmembrane domain.

PMID- 7629190
TI  - The propeptide of anglerfish preprosomatostatin-I rescues prosomatostatin-II from
      intracellular degradation.
AB  - Polypeptide hormones and neuropeptides are initially synthesized as precursors
      possessing one or several domains that constitute the propeptide. Previous work
      from our laboratory demonstrated that expression of anglerfish prosomatostatin-I
      (proSRIF-I) in rat anterior pituitary GH3 cells resulted in efficient and
      accurate cleavage of the prohormone to generate the mature 14-amino acid peptide,
      SRIF-I. We also implicated the propeptide in mediating intracellular sorting to
      the trans Golgi network where proteolytic processing is initiated. In contrast,
      expression of a second form of the precursor, proSRIF-II in GH3 cells resulted in
      its intracellular degradation in an acidic, post-trans Golgi network compartment,
      most probably lysosomes. To further investigate the positive sorting signal
      present in proSRIF-I, we constructed a chimera comprising the signal peptide and
      proregion of SRIF-I fused to proSRIF-II and expressed the cDNA in GH3 cells. Here
      we demonstrate that the propeptide of SRIF-I rescued proSRIF-II from
      intracellular degradation quantitatively and diverted it to secretory vesicles.
      Furthermore, the chimera was processed to SRIF-28, an amino-terminally extended
      form of the hormone that is the physiological cleavage product of proSRIF-II
      processing in vivo. Most significantly, the SRIF-I propeptide functioned only in
      cis as part of the fusion protein and not in trans when expressed as a separate
      polypeptide. These data suggest that the SRIF-I propeptide may possess a sorting
      signal for sequestration into the secretory pathway rather than functioning as an
      intramolecular chaperone to promote protein folding.

PMID- 7629191
TI  - Transcriptional regulation of the genes encoding cytochromes P450BM-1 and P450BM
      3 in Bacillus megaterium by the binding of Bm3R1 repressor to Barbie box elements
      and operator sites.
AB  - We previously reported (Liang, Q., He, J.-S., and Fulco, A.J. (1995) J. Biol.
      Chem. 270, 4438-4450) that Bm3R1, a repressor regulating the expression of P450BM
      3 in Bacillus megaterium, could bind to Barbie box sequences in the 5'-flanking
      regions of barbiturate-inducible genes. We've now shown that pentobarbital does
      not inhibit in vitro binding of Bm3R1 to the P450BM-3 and P450BM-1 Barbie boxes
      (BB3 and BB1), although the palindromic operator sequence (OIII) of P450BM-3 did
      have a strong competitive effect on such binding. G39E-Bm3R1, a mutant of Bm3R1,
      did not bind to either Barbie box. In the presence of Bm3R1, portions of the
      regulatory regions of P450BM-3 and P450BM-1 were protected from DNase I
      digestion. These included 11 of the 15 base pairs of BB3 plus 7 base pairs 3' to
      BB3, BB1 plus 16 base pairs 3' to BB1, and, in the 5'-flanking region of P450BM
      1, segments covering most of two palindromic sequences (OII and OIII) of 24 and
      52 base pairs. These DNase I-protected regions (including OIII) showed
      considerable sequence identity, especially in a conserved poly(A) motif.
      Barbiturates did not inhibit binding of Bm3R1 to OI. OII in vitro while G39E
      Bm3R1 did not bind. The regulatory effects of Bm3R1 on P450BM-1 and P450BM-3 were
      also evaluated in vivo using heterologous chloramphenicol acetyltransferase
      constructs and Western blotting. In the G39E mutant strain, both P450BM-1 and
      P450BM-3 were constitutively expressed, and the regulatory proteins Bm1P1 and
      Bm3P1, although still pentobarbital-inducible, had significantly higher basal
      levels of synthesis. In toto, our results show that Bm3R1 represses both P450BM-1
      and P450BM-3 expression and that it may effect this by coordinate binding to
      operator and Barbie box sequences to produce looping of the P450BM-1 and P450BM-3
      regulatory regions through protein-protein interaction.

PMID- 7629192
TI  - The molecular cloning and characterization of BM1P1 and BM1P2 proteins, putative
      positive transcription factors involved in barbiturate-mediated induction of the
      genes encoding cytochrome P450BM-1 of Bacillus megaterium.
AB  - Analysis of a 1.3-kilobase segment of 5'-flanking DNA from the barbiturate
      inducible P450BM-1 gene (CYP106) of Bacillus megaterium revealed two open reading
      frames. One, BM1P1, encodes 98 amino acids and is located 267 base pairs upstream
      from the sequence encoding cytochrome P450BM-1 but in the opposite orientation.
      The second, BM1P2 (88 amino acids), is 892 base pairs upstream from the P450BM-1
      coding sequence and in the same coding strand. The expression of BM1P1 and BM1P2
      was strongly stimulated in cells grown in the presence of pentobarbital, and the
      BM1P1 gene product exerted positive control on expression of P450BM-1. When a 177
      base pair fragment encompassing the overlapping promoter regions of the P450BM-1
      and BM1P1 genes was used as a probe in DNA binding assays, the BM1P1 and BM1P2
      gene products and Bm3R1 (the repressor protein regulating the barbiturate
      mediated expression of P450BM-3) could bind individually, but the addition of
      BM1P1 or BM1P2 to a binding mixture containing Bm3R1 completely prevented the
      appearance of a Bm3R1 binding band. When a 208-base pair fragment containing a
      Barbie box sequence and located upstream of the 177-base pair fragment was used
      as a probe, only a Bm3R1 binding band was detected. Although neither BM1P1 and
      BM1P2 appeared to bind to this 208-base pair fragment, their presence strongly
      inhibited the binding of Bm3R1 to the same probe. The evidence suggests that
      BM1P1 and BM1P2 may, in part, act as positive regulatory proteins involved in the
      expression of the P450BM-1 gene by interfering with the binding of the repressor
      protein, Bm3R1, to the regulatory regions of P450BM-1.

PMID- 7629193
TI  - Epidermal growth factor induces H+,K+-ATPase alpha-subunit gene expression
      through an element homologous to the 3' half-site of the c-fos serum response
      element.
AB  - Epidermal growth factor (EGF) acutely inhibits acid secretion; however, prolonged
      administration of EGF has been reported to increase acid production. We undertook
      these studies to examine whether the physiological effects of EGF on acid
      secretion are mediated by regulation of gastric H+,K+-ATPase, the principle
      enzyme responsible for acid secretion. EGF in concentrations equivalent to those
      in plasma increased H+,K(+)-ATPase alpha-subunit mRNA levels. Using H+,K(+)
      ATPase-luciferase constructs transfected into primary cultured parietal cells, a
      significant step up in EGF inducibility was observed between bases -162 and -156
      (5'-GACATGG-3') relative to the cap site. This EGF response element (ERE)
      conferred EGF inducibility when linked to homologous and heterologous promoters.
      The ERE is homologous to the 3' half-site of the c-fos serum response element to
      which rNFIL-6, rE12, and SRE-ZBP bind. Electrophoretic mobility shift assays
      using an ERE probe and parietal cell nuclear extracts revealed a specific DNA
      protein complex, the formation of which was changed by neither E12 and NFIL-6
      consensus oligonucleotides nor antibodies for NFIL-6, SRE-ZBP, and E12. Our
      studies indicate that EGF induces gastric H+,K(+)-ATPase alpha-subunit gene
      expression via an interaction between a specific ERE and a novel transcriptional
      factor and that this may be a physiologic mechanism by which EGF regulates acid
      secretion.

PMID- 7629194
TI  - Physical characterization of gap junction membrane connexons (hemi-channels)
      isolated from rat liver.
AB  - Enriched subcellular fractions of double membrane gap junctions (plaques) from
      rat livers were treated under reducing conditions with high salt and non-ionic
      detergent concentrations at high pH to obtain a preparation of structural 80-90 A
      complexes of oligomers (connexons). The isolated oligomers were
      chromatographically purified, and subsequently characterized immunologically,
      morphologically by electron microscopy, hydrodynamically by gel filtration and
      ultracentrifugation, spectroscopically by circular dichroism, and chemically via
      cross-linking studies. The physical characteristics of these isolated gap
      junction complexes were compared to those of native membrane-bound gap junctions
      in rat liver. These analyses indicate that the isolated complex (connexon)
      principally contains a hexameric arrangement of gap junction protein to form a
      single membrane hemi-channel.

PMID- 7629195
TI  - Molecular characterization of cDNA encoding a novel protein related to
      transcriptional enhancer factor-1 from neural precursor cells.
AB  - We identified a novel cDNA related to that of transcriptional enhancer factor-1
      (TEF-1) during the course of isolation and characterization of cDNAs, whose mRNAs
      are preferentially expressed in the mouse neural precursor cells. The putative
      polypeptide, termed embryonic TEA domain-containing factor (ETF), deduced from
      the nucleotide sequence contains 445 amino acids and shares 66% amino acid
      identity with mouse and human TEF-1 proteins. The primary structure of the TEA
      domain, a probable DNA-binding domain, and the specific DNA binding activity to
      the GT-IIC motif of ETF are indistinguishable from those of the known vertebrate
      TEF-1 proteins. However, the expression of the ETF gene is strictly regulated in
      developing embryos and is limited to certain tissues, such as the hindbrain of a
      10-day-old mouse embryo, in contrast to the ubiquitous expression pattern of the
      TEF-1 gene. These results suggest that ETF is a novel mammalian member of the TEA
      domain-containing transcription factor family and may be involved in the gene
      regulation of the neural development. We have discussed the possible existence of
      multiple subtypes of the mammalian TEF-1 family proteins, which may play
      different roles in cellular and development gene regulation.

PMID- 7629196
TI  - Activation of Jun kinase/stress-activated protein kinase by GTPase-deficient
      mutants of G alpha 12 and G alpha 13.
AB  - Signal transduction pathways regulated by G12 and G13 heterotrimeric G proteins
      are largely unknown. Expression of activated, GTPase-deficient mutants of alpha
      12 and alpha 13 alter physiological responses such as Na+/H+ exchanger activity,
      but the effector pathways controlling these responses have not been defined. We
      have found that the expression of GTPase-deficient mutants of alpha 12 (alpha
      12Q229L) or alpha 13 (alpha 13Q226L) leads to robust activation of the Jun
      kinase/stress-activated protein kinase (JNK/SAPK) pathway. Inducible alpha
      12Q229L and alpha 13Q226L expression vectors stably transfected in NIH 3T3 cells
      demonstrated JNK/SAPK activation but not extracellular response/mitogen-activated
      protein kinase activation. Transient transfection of alpha 12Q229L and alpha
      13Q226L also activated the JNK/SAPK pathway in COS-1 cells. Expression of the
      GTPase-deficient mutant of alpha q (alpha qQ209L) but not alpha i (alpha iQ205L)
      or alpha s (alpha sQ227L) was also able to activate the JNK/SAPK pathway.
      Functional Ras signaling was required for alpha 12Q229L and alpha 13Q226L
      activation of the JNK/SAPK pathway; expression of competitive inhibitory N17Ras
      inhibited JNK/SAPK activation in response to both alpha 12Q229L and alpha
      13Q226L. The results describe for the first time a Ras-dependent signal
      transduction pathway involving JNK/SAPK regulated by alpha 12 and alpha 13.

PMID- 7629197
TI  - Phosphorylation and activation of beta-adrenergic receptor kinase by protein
      kinase C.
AB  - The aim of this study was to test the possible modification of beta-adrenergic
      receptor kinase (beta ARK) activity by second messengers and/or their downstream
      components. Using human mononuclear leukocytes (MNL), we found that calcium
      ionophores could elevate beta ARK activity by about 80% in a protein kinase C
      (PKC)-dependent manner. This was confirmed by the ability of the PKC activator
      phorbol 12-myristate 13-acetate (PMA) to produce a similar effect, suggesting a
      PKC-dependent modulation of beta ARK activity. In vitro experiments with purified
      proteins showed that PKC could directly phosphorylate beta ARK1 with an apparent
      Km for beta ARK1 of 6 nM. The ability of beta ARK1 to phosphorylate rhodopsin was
      61% greater when it was phosphorylated by PKC. The level of phosphorylation of
      beta ARK1 immunoprecipitated from MNL and Sf9 cells overexpressing this kinase
      was enhanced by about 2-3-fold after PMA treatment. Functional significance of
      PKC-dependent increase in beta ARK activity ws demonstrated by beta-adrenergic
      receptor (beta AR) homologous desensitization experiments in MNL. beta AR
      desensitization, as induced by exposure to 10 microM isoproterenol (5 min at 37
      degrees C), was increased from 42 +/- 10% in control to 68 +/- 8% in PMA
      pretreated MNL. beta ARK inhibitor heparin (160 micrograms/ml) prevented the
      augmenting effect of PMA on beta AR desensitization. These results show that beta
      ARK activity can be increased through phosphorylation by PKC, thus indicating
      that beta ARK can be preconditioned to modulate the subsequent cellular
      responsiveness to receptor activation, providing the cell with a mechanism by
      which specific homologous desensitization can be regulated heterologously.

PMID- 7629198
TI  - Proteoglycan-mediated inhibition of A beta proteolysis. A potential cause of
      senile plaque accumulation.
AB  - Senile plaques of Alzheimer's disease brain contain, in addition to beta amyloid
      peptide (A beta), multiple proteoglycans. Systemic amyloidotic deposits also
      routinely contain proteoglycan, suggesting that these glycoconjugates are
      generally involved in amyloid plaque formation and/or persistence. We demonstrate
      that heparan sulfate proteoglycan (HSPG) and chondroitin sulfate proteoglycan
      (CSPG) inhibit the proteolytic degradation of fibrillar, but not non-fibrillar, A
      beta at physiological pH. In accordance with the proteolysis studies, high
      affinity binding of proteoglycans to fibrillar A beta(1-40) and A beta(1-42) is
      observed from pH 4 to 9, whereas appreciable binding of HSPG or CSPG to non
      fibrillar peptide is only seen at pH < 6. This differing pH dependence of binding
      suggests that a lysine residue is involved in proteoglycan association with
      fibrillar A beta, whereas a protonated histidine appears to be needed for binding
      of the glycoconjugates to non-fibrillar peptide. Scatchard analysis of fibrillar
      A beta association with proteoglycans indicates a single affinity interaction,
      and the binding of both HSPG and CSPG to fibrillar A beta is completely inhibited
      by free glycosaminoglycan chains. This implies that these sulfated carbohydrate
      moieties are primarily responsible for proteoglycan.A beta interaction. The
      ability of proteoglycans to bind fibrillar A beta and inhibit its proteolytic
      degradation suggests a possible mechanism of senile plaque accumulation and
      persistence in Alzheimer's disease.

PMID- 7629199
TI  - Efficient inhibition of activation-induced Fas ligand up-regulation and T cell
      apoptosis by retinoids requires occupancy of both retinoid X receptors and
      retinoic acid receptors.
AB  - Two retinoic acid (RA) receptors, retinoic acid receptors (RARs) and retinoid X
      receptors (RXRs), have been identified. All-trans-RA and its 9-cis-isomer are
      ligands for RARs, but only 9-cis-RA binds RXRs with high affinity. Activation
      induced T cell hybridoma death is mediated via the engagement of Fas by
      activation-up-regulated Fas ligand, and RA prevents this type of apoptosis by
      inhibiting the induction of Fas ligand expression. To investigate the mechanism
      of RA action, T hybridoma cells were transfected with cDNA encoding RXR beta or
      dominant-negative RXR beta. Cells that overexpressed RXR beta were more sensitive
      to 9-cis-RA rescue from activation-induced death than cells transfected with
      vector alone. In contrast, cells expressing the dominant-negative RXR beta could
      not be rescued from death with 9-cis-RA. In wild type cells, an RAR-selective
      synthetic retinoid had little effect on activation-induced apoptosis, while an
      RXR-selective agonist prevented apoptosis but only at concentrations about
      approximately 10-fold greater than that required for 9-cis-RA. Simultaneous
      addition of the RAR- and RXR-selective retinoids completely prevented activation
      induced apoptosis at concentrations where either alone had relatively little
      protective effect. The same hierarchy of efficacy was found for activation
      induced Fas ligand expression. These data demonstrate that binding of both RARs
      and RXRs is required for efficient inhibition of activation-induced Fas ligand
      upregulation and T cell apoptosis by retinoic acid.

PMID- 7629200
TI  - Folding of human intestinal lactase-phlorizin hydrolase.
AB  - The folding of human intestinal prolactase-phlorizin hydrolase (pro-LPH) has been
      analyzed in a cell-free transcription/translation system. In the presence of the
      thiol oxidant GSSG, disulfide bond formation in pro-LPH can be promoted
      concomitant with the binding of the molecule to a conformation-specific
      monoclonal anti-LPH antibody. Under these conditions, pro-LPH does not bind to
      the molecular chaperone BiP. In the absence of GSSG, on the other hand, pro-LPH
      does not bind to the monoclonal anti-LPH antibody, but can be immunoprecipitated
      with a polyclonal antibody that is directed against a denatured form of the
      enzyme. In this case, interaction of pro-LPH with immunoglobulin heavy chain
      binding protein can be discerned. The results demonstrate the existence of
      intramolecular disulfide bonds that are essential for the promotion of pro-LPH to
      a native conformation. Furthermore, BiP is involved in the folding events of pro
      LPH.

PMID- 7629201
TI  - Long-range fragmentation of the eukaryotic genome by exogenous and endogenous
      nucleases proceeds in a specific fashion via preferential DNA cleavage at matrix
      attachment sites.
AB  - Small cell lung cancer cells (OC-NYH-VM) were permeabilized and treated with
      different nucleases. The long-range distribution of DNA cleavage sites in the
      amplified c-myc gene locus was then analyzed by pulsed field gel electrophoretic
      separation of the released 50-kilobase to 1-megabase DNA fragments followed by
      indirect end labeling. Exogenous DNase I and nucleases specific for the single
      stranded DNA were found to generate similar nonrandom patterns of large DNA
      fragments. The cleavage sites were located close to or even colocalized with
      matrix attachment regions, which were mapped independently using a recently
      developed procedure for DNA loop excision by DNA topoisomerase II-mediated DNA
      cleavage. Endogenous acidic nuclease with the properties of DNase II also
      digested DNA preferentially in proximity to the matrix attachment regions,
      generating characteristic patterns of excised DNA loops and their oligomers. A
      similar, although less specific, pattern of DNA fragmentation was observed after
      incubation of permeabilized cells under conditions favoring the activity of
      endogenous neutral Ca(2+)- and Mg(2+)-dependent nucleases. These findings are
      discussed in the context of the current model of the spatial domain organization
      of eukaryotic genome.

PMID- 7629202
TI  - Expression of the human 5-hydroxytryptamine1A receptor in Sf9 cells.
      Reconstitution of a coupled phenotype by co-expression of mammalian G protein
      subunits.
AB  - The possibility that Spodoptera frugiperda (Sf9) cells can provide an intact cell
      setting for reconstitution of the human 5-hydroxytryptamine1A (5-HT1A) receptor
      with mammalian G protein subunits was explored. The 5-HT1A receptor was found to
      assume an uncoupled phenotype when expressed alone in Sf9 cells at relatively
      high levels (5-34 pmol of receptor/mg of membrane protein), i.e. agonist-binding
      to the receptor was characterized by a relatively high Kd and an insensitivity to
      GTP. Co-expression of the receptor with members of the alpha i "family" together
      with various combinations of beta 1 and gamma subunits increased the affinity for
      agonists to that observed for the coupled form of receptor in mammalian cells,
      concomitant with conferrance of guanosine 5'-(beta,gamma-imino)triphosphate
      sensitivity. The agonists employed were [3H]8-hydroxy-N,N-dipropyl-2
      aminotetralin ([3H]8-OH-DPAT) and [125I]R(+)-trans-8-hydroxy-2-[N-n-propyl-N-(3'
      iodo-2'-propenyl) amino]tetralin ([125I]8-OH-PIPAT). The binding of an
      antagonist, [125I]4-(2'-methoxyphenyl)-1-[2'-[N-(2"- pyridinyl)-p
      iodobenzamido]ethyl]piperazine ([125I]p-MPPI), was unaffected by co-expression of
      G protein subunits. Both alpha and beta gamma subunits were required for optimal
      coupling. No differences were evident among alpha i1, alpha i2, alpha i3, alpha
      o, and alpha z when expressed with beta 1 gamma 2 in this regard, nor among most
      permutations of beta 1 gamma subunits when expressed with alpha i1 (beta 1 gamma
      2 approximately beta 1 gamma 3 approximately beta 1 gamma 5 > beta 1 gamma 1).
      Alpha s and alpha q expressed with beta 1 gamma 2 did not participate in
      coupling. These data support the conclusion that normal interactions between a
      mammalian receptor and a select array of G proteins can be established in intact
      Sf9 cells, and extend previous observations of 5-HT1A receptor coupling to G(o)
      and the pertussis toxin-insensitive G protein Gz.

PMID- 7629203
TI  - Angioscopy guided in situ bypass versus angioscopy guided non reversed bypass for
      infrainguinal arterial reconstructions. A comparison of outcome.
AB  - In situ bypass grafting depends on an adequate ipsilateral greater saphenous
      vein. To profit from a tapered, valveless conduit in legs without an adequate
      greater saphenous vein, we routinely used the contralateral saphenous vein non
      reversed. In some reconstructions to the infrageniculate popliteal and the
      proximal anterior tibial artery we used the non reversed instead of the in situ
      technique because of the distance between the natural course of the saphenous
      vein and the recipient artery. This retrospective study compares the outcome of
      48 in situ bypasses to the outcome of 66 non reversed bypasses. Endoluminal
      manipulations in all veins were visually controlled using an angioscope. The two
      groups of bypasses (in situ versus non reversed) did not differ concerning age,
      sex, risk factors, operative mortality, indication for surgery and distribution
      of the recipient arteries. There was a tendency for a lower wound complication
      rate in "in situ" compared to non reversed bypasses (10% versus 27%; p = 0.086).
      There were no differences in cumulative primary and primary assisted patency
      rates between the two groups after two years. We prefer the angioscopy guided in
      situ technique for reconstructions to infrageniculate arteries because of a low
      wound complication rate and excellent patency rates. In the absence of an
      adequate ipsilateral saphenous vein and in reconstructions to recipient arteries
      not presenting themselves for the in situ technique, similar results can be
      achieved with angioscopically prepared non reversed grafts.

PMID- 7629204
TI  - The pressure/volume relationship of the calf: a measurement of vein compliance?
AB  - OBJECTIVES: The role of compliance changes in the patho-physiology of venous
      disease is not well known mainly because of difficulty to measure compliance of
      veins in situ. This study suggests a method to determine the calf pressure/volume
      relationship by utilizing venous occlusion plethysmography combined with dorsal
      vein pressure. DESIGN: Comparison between two techniques of measuring calf
      pressure/volume relationship using air plethysmography with validation against
      popliteal vein diameter changes detected by duplex ultrasound. SETTING Vascular
      laboratory. MATERIALS: In 6 normal and 6 radiographically confirmed post
      thrombotic lower limbs, the calf pressure/volume relationship was determined. The
      dorsal vein pressure was continuously recorded. Simultaneously calf volume
      changes were obtained by an air plethysmograph during venous occlusion
      plethysmography (outflow slope coefficient) and fractionated tilting of the
      subject from erect to supine position (volume at 40 mmHg). During the tilt,
      sagittal diameter of the popliteal vein was measured (% change/mmHg =
      distensibility). RESULTS: The outflow pressure/volume slope coefficient
      correlated significantly with the volume at 40 mmHg during tilt maneuver (r =
      0.92) and the popliteal vein distensibility (r = 0.86). Variations in arterial
      inflow, venous outflow obstruction, or reflux did not affect the occlusion
      plethysmographic method. Plethysmographic changes related directly to venous
      volume changes, i.e. vein expansion suggesting that the pressure/volume
      relationship described vein compliance. CONCLUSION: The result show a direct
      relationship between the pressure/volume curve of the calf and deep vein
      distention. Shifts of the pressure/volume curve are likely to be mainly caused by
      vein wall changes, but other factors (e.g. condition of surrounding tissue,
      reduced venous volume) may also contribute and this needs further investigation.

PMID- 7629205
TI  - Compliance of the normal and post-thrombotic calf.
AB  - OBJECTIVE: In addition to degree of outflow obstruction and reflux and poor calf
      muscle pump function, vein wall compliance changes are important in understanding
      pathophysiology of venous disease. This study compares the pressure/volume
      relationship in post-thrombotic and healthy legs. EXPERIMENTAL DESIGN:
      Prospective and comparative study. SETTING: Vascular laboratory. PARTICIPANTS:
      Investigations were performed on 24 apparently normal legs and 30 post-thrombotic
      limbs as confirmed by phlebography. METHOD: Dorsal vein pressure and absolute
      calf volume decrease were recorded simultaneously during outflow form the leg
      after release of the cuff during venous occlusion air-plethysmography with and
      without reactive hyperemia. The slope of the pressure/volume outflow curve was
      calculated. In addition, the distensibility (= collapsibility) was determined as
      % volume decrease/mmHg. The popliteal and femoral vein diameters were measured in
      supine and erect position by ultrasound. RESULTS: With and without induced
      hyperemia the mean slope coefficients of post-thrombotic legs were significantly
      higher (0.52 +/- 0.22 and 0.53 +/- 0.18) than in normal (0.15 +/- 0.10 and 0.29
      +/- 0.11), i.e., the curve steeper since the calf was stiffer, less compliant.
      The degree of outflow obstruction and severity of skin changes did not affect the
      slope measurement substantially. Collapsibility during venous outflow was
      significantly less in post-thrombotic legs. The post-thrombotic veins were less
      distended on standing. CONCLUSIONS: Post-thrombotic calves are less compliant
      than normal legs mainly due to less compliance of the vein wall, although
      theoretically reduced venous volume may contribute.

PMID- 7629206
TI  - Diagnosis and surgical treatment of the carotid body tumors.
AB  - Resection of carotid body tumors can be difficult to perform because of its site,
      vascularity, arterial adherence and local cranial nerve involvement. Advances in
      vascular surgical technique have reduced the risks of perioperative complications
      such as carotid injury, stroke and death. From January 1980 to May 1994 20
      patients (22 carotid body tumors) were examined. All patients except one were
      evaluated with a preoperative angiography. No preoperative embolization was
      performed. Thirteen patients underwent ultrasonography, nine a CT scan of the
      neck, 5 magnetic resonance scanning and two magnetic resonance angiography. One
      old patient refused operation. The authors report their experience on 21 carotid
      body tumor resections (14 Shamblin group I and 7 group II paragangliomas).
      Surgical technique is based on subadventitial resection (18 excisions) and 3
      resections were performed from the medial surface of the carotid bifurcation
      which had been partially absorbed into the mass. In the last 15 operations
      intraoperative Somatosensorial Evoked Potential (SEP) monitoring has been used.
      Only two patient required arterial repair because intimal dissection and another
      patient needed vagus nerve section. The ligation of external carotid artery and
      internal carotid resection with graft replacement were never necessary in these
      patients. No early or late deaths occurred and no recurrences were detected at
      follow-up.

PMID- 7629207
TI  - Renal revascularization in patients on dialysis.
AB  - Five patients requiring dialysis for acute pulmonary edema and uremia from severe
      renal artery occlusive disease underwent surgical revascularization. Three
      patients with oliguria had excellent outcomes and remain dialysis-independent as
      long as twenty-four months following operation (mean serum creatinine 2.0 mg/dl).
      The two patients who were anuric both had technically successful operations but
      remained dialysis-dependent. Diagnostic evaluation of the azotemic patient
      suspected to have renal arterial occlusive disease should include a history and
      physical examination, urinalysis, renal ultrasound, and duplex scan of the renal
      arteries. In appropriate patients, arteriography should then be considered if
      other diagnoses appear unlikely. This algorithm may help identify those patients
      who might benefit from renal revascularization. It appears that oliguria rather
      than anuria and the angiographic demonstration of a patent distal vessel and
      nephrogram suggest a better functional outcome after revascularization.
      Unfortunately, the response to surgery cannot be reliably predicted and patient
      selection remains a challenge, but retrieval of renal function can be achieved in
      some cases even if patients are already being hemodialyzed.

PMID- 7629208
TI  - Vertebral artery dissection. Case report.
AB  - Vertebral artery dissection is an uncommon but important cause of posterior
      stroke in young and middle aged adults. We report a case with a long term
      fluctuating ischemic symptoms due to bilateral spontaneous dissection. Etiology
      and treatment are discussed.

PMID- 7629209
TI  - Valvular replacement for aortic stenosis on patients in NYHA class III and IV.
      Early and long term results.
AB  - From January 1972 to June 1990, 112 patients between 39 and 83 years old, divided
      into 68 NYHA class III (60.72%) and 44 NYHA class IV, underwent surgery for
      aortic stenosis. There were 67 male (59.82%) and 45 female (40.18%). Early
      mortality included 8 patients (7.14%). Actuarial survival (including early
      postoperative mortality) for all 112 patients was 88.39%, 77.67%, 67.85% and
      65.7% t one year, five, ten and fifteen years respectively. Clinical criteria are
      subjective but they remain the best prognostic factor. Surgery is indicated at
      occurrence of first symptoms, but, even in advanced cases, aortic valvular
      replacement can significantly improve survival and functional status. Even if
      operative risk is increased and secondary cardiomyopathy often progresses after
      surgery, aortic valve replacement results seem better than those of medical
      treatment alone.

PMID- 7629210
TI  - Complete arterial myocardial revascularization using the right gastroepiploic
      artery and both internal thoracic arteries as pedicled grafts.
AB  - To achieve complete arterial myocardial revascularization without vein grafts,
      the right gastroepiploic artery and both internal thoracic arteries were used as
      pedicled grafts in 105 patients from March 1989 to July 1994. There were 101 male
      and 4 female patients, with a mean age of 51 years (range 32 to 65 years). Three
      vessels disease was present in all patients. Six patients underwent previous
      bypass procedures with the use of vein grafts. A total of 363 distal anastomosis
      (108 with the right gastroepiploic artery, 255 with both internal thoracic
      arteries) were constructed. The mean number of distal anastomoses was 3.4. There
      was no hospital mortality. Seven patients required a rethoracotomy: 5 because of
      post-operative signs of ischemia, 2 because of bleeding. In one patient a
      splenectomy had to be performed because of bleeding. A new Q wave was noted in 2
      patients. Follow-up averaged 21 months (range 1 to 67 months). Ninety nine (95%)
      of the patients were in NYHA class I, 6 (5%) in class II. No late complications
      were noted. We conclude that, complete myocardial revascularization using the
      right gastroepiploic artery in combination with both internal thoracic arteries
      as pedicled grafts can be achieved in selected patients with excellent mid term
      results.

PMID- 7629211
TI  - Coronary artery damage during mitral valve replacement.
AB  - An anatomic study of 15 hearts has assessed the existing correlations between the
      mitral annulus and coronary arteries. The circumflex artery is sometimes located
      very close to the mitral annulus, as close as one millimetre, hence there is a
      risk of injury during mitral valvular replacement. This risk is especially when
      coronaries have a prevailing left anatomic position or a balanced coronary
      system.

PMID- 7629212
TI  - Sestamibi imaging and echocardiography: a combined approach to myocardial
      infarction.
AB  - The resting relationship of MIBI segmental uptake to regional wall motion has
      been studied in 30 patients with postinfarction wall motion abnormalities. The
      purpose of this study was to verify whether an integrated approach using
      Sestamibi (MIBI) imaging (perfusion analysis) combined with echocardiography
      (ECHO) (wall motion analysis) could present an additive value to differentiate
      infarcted from viable myocardial areas with respect to MIBI imaging alone. The
      same 11 segments model for left ventricle was used to compare segmental wall
      motion scores versus segmental uptake scores using a chi 2 analysis. The global
      score frequency rates for MIBI and ECHO were examined and a subsequent
      comparative analysis score versus score on each segment was performed. Our data,
      based on a chi 2 analysis, indicated that MIBI imaging overestimates the
      effective area of necrosis, underestimating, furthermore, hypoperfused but non
      necrotic myocardium. We can conclude that an integrated approach based on both
      segmental perfusion and wall motion analysis, seems to be clinically suitable for
      a correct evaluation of infarcted patients, especially in view of
      revascularization procedures, providing an additive value in discriminative
      capacity, with respect to MIBI scintigraphic analysis alone.

PMID- 7629213
TI  - Complicated removal of a hydatid cyst of the interventricular septum.
AB  - In a 27-year-old woman with a large hydatid cyst of the liver, an asymptomatic
      cardiac cyst located in the interventricular septum was discovered as well. The
      diagnosis was based upon echocardiography, computerized axial tomography and
      nuclear magnetic resonance. There was no evidence of damage to the
      atrioventricular conduction system or to the cardiac valves. At operation,
      however, the left posterior papillary muscle and chordae were firmly adherent to
      the cyst. Patch closure of the resulting ventricular septal defect, and mitral
      valve and chordae repair were necessary. The patient is alive and well 6 months
      after the operation, with mild residual mitral regurgitation. Precise anatomical
      delineation of the hydatid cyst localization within the heart, particularly in
      the interventricular septum, and its relations with the various cardiac
      structures is a difficult task, in spite of all the imaging techniques available.
      The surgical approach therefore has to be very careful and mindful of the
      potential complications.

PMID- 7629214
TI  - Acute aortic dissection, aortic insufficiency, and a single coronary artery in a
      patient with Turner's syndrome.
AB  - A rare case of acute aortic dissection and aortic regurgitation in a patient with
      Turner's syndrome is reported. A 25-year-old woman with a history of Turner's
      syndrome presented to our hospital with complaints of chest pain and dyspnea.
      Emergent surgery was performed after chest roentgenography and two-dimensional
      echocardiography. Intraoperatively, the patient was found to have a single
      coronary artery and a bicuspid aortic valve. The patient was treated successfully
      with a composite graft consisting of a 24 mm woven dacron graft, a 21 mm St. Jude
      Medical aortic prosthetic valve, and an equine pericardial skirt. The composite
      graft was inverted into the ascending aorta and connected to a small coronary
      artery graft. The patient's postoperative course was uneventful. A cardiac
      catheterization was performed postoperatively and revealed a competent
      anastomotic site and no evidence of aortic regurgitation. We provide a brief
      review of coronary anomalies and aortic diseases associated with patients with
      Turner's syndrome. The most commonly associated complications include coarctation
      of the aorta and bicuspid aortic valve disease. The incidence of coronary
      anomalies in patients with Turner's syndrome is maybe rare.

PMID- 7629215
TI  - Interruption of right sided aortic arch. Case report and review of the
      literature.
AB  - Interrupted right sided aortic arch is a very rare anomaly, and to our knowledge
      only one such case in which the patient underwent complete repair has been
      recorded in the literature. Twelve additional cases were found on autopsy or
      underwent palliative surgery. We present the case of a 25-day-old infant with an
      interrupted right sided aortic arch. The anomaly was repaired by a one-stage
      surgical approach, and the patient discharged from the hospital. Surgical
      technique considerations are discussed.

PMID- 7629216
TI  - Subaortic left ventricular pseudoaneurysm of obscure origin.
AB  - Subaortic pseudoaneurysms of the left ventricle are rare acquired cardiac
      defects. They are usually associated with previous valve surgery, trauma, or
      aortic valve endocarditis. We describe the appearance of subaortic pseudoaneurysm
      10 years after left heart catheterization in a patient with both aortic stenosis
      and regurgitation. The differential diagnosis of such lesions is presented.

PMID- 7629217
TI  - Fatal oesophageal ulceration due to left atrial enlargement.
AB  - Aorto-oesophageal fistula is a rare condition. We describe a patient with such a
      fistula secondary to oesophageal ulceration, which in itself was due to left
      atrial enlargement.

PMID- 7629218
TI  - Tracheal rupture during transhiatal esophagectomy and anaesthetic problems. A
      case report.
AB  - Tracheal rupture is a rare but potentially serious complication of transhiatal
      esophagectomy (THE). In this situation, ventilation of the patient can be
      extremely difficult, even impossible, due to excessive gas leakage from tracheal
      tear. In this case report, we present such a patient in whom emergency
      thoracotomy and patching of the trachea were performed in order to maintain
      ventilation and oxygenation.

PMID- 7629219
TI  - Gastric outlet obstruction of intrathoracic stomach.
AB  - Two rare cases of organic outlet obstruction of intrathoracic stomach following
      Ivor Lewis oesophagectomy are presented. Aetiology and the management of the same
      is discussed.

PMID- 7629220
TI  - Clinical review 72: diagnosis and management of functioning islet cell tumors.
AB  - Functional islet cell tumors cause recognizable clinical syndromes based on the
      peptide products they secrete (Table 1). Frequently, the diagnosis of these
      tumors is delayed. A high index of suspicion coupled with the use of appropriate
      biochemical and provocative tests should lead to earlier diagnosis. A suggested
      management plan for patients suspected of having an islet cell tumor is shown in
      Fig. 1. Earlier diagnosis coupled with advances in preoperative and
      intraoperative localization techniques have resulted in an increased number of
      patients being cured.

PMID- 7629221
TI  - Bone mass, the mechanostat, and ethnic differences.

PMID- 7629222
TI  - The prismatic case of Creutzfeldt-Jakob disease associated with pituitary growth
      hormone treatment.

PMID- 7629223
TI  - Clinical case seminar: lymphocytic hypophysitis: clinicopathological findings.
AB  - This report describes the clinicopathological features of 16 patients with
      lymphocytic hypophysitis and compares the results with the published literature.
      There were 2 males and 14 females in this series. In 10 of the 14 females (71%),
      the presentation was associated with pregnancy. Nine patients (56%) presented
      with symptoms of an expanding pituitary sellar mass, 10 (63%) had anterior
      pituitary hypofunction, 3 had diabetes insipidus (19%). Progressive undiagnosed
      hypopituitarism led to the demise of 3 patients (19%). Hyperprolactinemia was
      encountered in 6 patients (38%), and elevated growth hormone levels (GH) resulted
      in IGF-1 excess in one patient. Computed tomography (CT) and magnetic resonance
      (MR) imaging revealed features of a pituitary mass mimicking an adenoma in 10
      cases (83%). Four patients (25%) had associated autoimmune thyroiditis.
      Morphologic examination of the pituitary and immunohistochemistry showed a
      polyclonal lymphoplasmacytic infiltrate as well as occasional neutrophils,
      eosinophils, and macrophages; the chronic inflammatory process resulted in focal
      or diffuse adenohypophysial destruction of variable severity with associated
      fibrosis. The inflammatory infiltrate involved the neurohypophysis in 2 cases and
      one of these patients had diabetes insipidus; the posterior lobe of two other
      patients with diabetes insipidus was not examined morphologically. We conclude
      that lymphocytic hypophysitis should be considered in the differential diagnosis
      of females with pituitary enlargement presenting in the peripartum period as well
      as those patients in whom pituitary hormone deficiency and/or excess is noted in
      association with a co-existing autoimmune disorder. This clinical suspicion
      should probably also be extended to include patients presenting with rapidly
      growing pituitary masses associated with compressive symptoms with or without
      pituitary hormone dysfunction. Because of the transient endocrine and compressive
      features of this condition in many instances, conservative treatment on the basis
      of clinical suspicion alone may obviate the need for aggressive pituitary
      surgery.

PMID- 7629224
TI  - Steroid 21-hydroxylase deficiency: genotype may not predict phenotype.
AB  - Steroid 21-hydroxylase deficiency is the most frequent cause of congenital
      adrenal hyperplasia. We have determined the 21-hydroxylase genotype in 197
      patients with congenital adrenal hyperplasia owing to 21-hydroxylase deficiency
      and assessed phenotypic characteristics based on 1) genital status with respect
      to virilization in females, 2) ACTH stimulation tests to evaluate the secretion
      of androgens and 17-hydroxyprogesterone, and 3) salt deprivation tests to
      precisely describe the phenotype with respect to aldosterone deficiency and salt
      wasting. After dividing our patients into 26 21-hydroxylase gene mutation
      identical groups, we found that, in general, the patient's phenotype matched the
      severity of the genotype. However, in 13 of these groups, the genotype did not
      always predict the phenotype, even within families. This study, has demonstrated
      that the 10 most common mutations observed in the 21-hydroxylase gene result in
      phenotypes that are not always concordant with the genotype.

PMID- 7629225
TI  - Structural and functional characterization of osteogenic growth peptide from
      human serum: identity with rat and mouse homologs.
AB  - The osteogenic growth peptide (OGP) was recently characterized in regenerating
      bone marrow. In experimental animals, OGP increases osteogenesis. Immunoreactive
      OGP (irOGP) in high abundance was demonstrated in normal animal serum mainly as
      an OGP-OGP-binding protein (OGPBP) complex. Here we show the presence of an OGP
      OGPBP system in normal human serum. The total irOGP content, of which the bound
      peptide comprises at least 80-90%, ranged from 480-4460 mumol/L, several orders
      of magnitude higher than that of other regulatory polypeptides. The steady
      state/total irOGP ratio declined between 23 and 49 yr of age. The bound irOGP,
      purified by boiling, ultrafiltration, and hydrophobic high pressure liquid
      chromatography, was identical to OGP obtained previously from rat regenerating
      marrow and mouse stromal cell cultures in terms of its amino acid sequence,
      immunoreactivity, and mitogenicity. These data demonstrate the usefulness of our
      immunoassay to measure circulating OGP. More importantly, the identity of the
      human OGP with that of other species indicates the peptide's evolutionary
      conservation and, thus, its biological importance. The natural occurrence of OGP
      in man signifies its potential role in the prevention of bone loss and rescue of
      bone mass, especially in osteoporosis.

PMID- 7629226
TI  - Lysine vasopressin stimulation of cortisol secretion in patients with
      adrenocorticotropin-independent macronodular adrenal hyperplasia.
AB  - We present two patients with Cushing's syndrome due to ACTH-independent
      macronodular adrenal hyperplasia who showed marked plasma cortisol response to
      lysine-8-vasopressin (LVP) injection (from 930 and 731 pmol/L to 2177 and 1920
      pmol/L, respectively), while plasma ACTH levels remained undetectable. The ACTH
      independence of cortisol secretion in the two patients was determined from the
      following endocrinological findings. Plasma cortisol levels were not increased by
      corticotropin-releasing hormone injections and were not suppressed by high dose
      (16 mg) dexamethasone administrations. The plasma ACTH levels, measured by two
      independent sensitive immunoassays, were persistently undetectable even after
      corticotropin-releasing hormone injection, metyrapone administration, and
      bilateral adrenalectomy. The particular pathological finding of the two cases,
      atrophic lesions in nonnodular parts of the adrenal cortexes, also indicated ACTH
      independence of the macronodular hyperplasia. In vitro examination revealed a
      direct effect of LVP on cortisol secretion from the adrenal cells of the
      macronodules. We also examined seven patients with Cushing's syndrome caused by
      adrenal adenoma and found a statistically significant plasma cortisol response to
      LVP injection. The direct effect of LVP was also demonstrated in cultured adenoma
      cells. In conclusion, we discovered a direct adrenal effect of LVP on cortisol
      secretion in patients with ACTH-independent macronodular hyperplasia and, to a
      lesser extent, in patients with cortisol-producing adrenal adenoma. The cortisol
      response to LVP may serve to facilitate their diagnosis and choice of therapy.

PMID- 7629227
TI  - Some forms of big big prolactin behave as a complex of monomeric prolactin with
      an immunoglobulin G in patients with macroprolactinemia or prolactinoma.
AB  - The purpose of this study was to characterize the structure of big big PRL (bb
      PRL) in patients with macroprolactinemia or prolactinomas. Serum samples from
      these patients were fractionated by Sephadex G-100 chromatography, and PRL was
      measured in the eluate by an immunoradiometric assay. The fractions containing bb
      PRL were subjected to affinity chromatography with an antihuman immunoglobulin G
      (IgG) agarose column. PRL and IgG were assayed in the fractions obtained after
      affinity chromatography by immunoradiometric assay and radial immunodiffusion,
      respectively. bb-PRL was also immunoprecipitated with an antihuman PRL antibody,
      followed by polyacrylamide gel electrophoresis and Western blotting. We found
      that an average of 60% (range, 27-87%) of bb-PRL from patients with
      macroprolactinemia was retained by the agarose, indicating that this form of PRL
      contains an IgG. In one of the patients with prolactinoma, the big big form
      constituted 76% of the total PRL immunoreactivity. Most (75%) of the bb-PRL from
      this patient behaved as an IgG after affinity chromatography. In the two other
      patients with prolactinoma, we found that 22% and 25% of the bb-PRL, which
      represented only 2% and 3% of the total PRL in the serum, reacted as an IgG. In
      both groups of patients, the 23-kilodalton form of PRL was detected after the
      immunoprecipitation of bb-PRL. These results show that bb-PRL is in part a
      complex of 23-kilodalton PRL with an IgG and not an antibody mimicking the
      actions of PRL, as has been demonstrated for some large forms of growth-hormone.

PMID- 7629228
TI  - Phenytoin increases markers of osteogenesis for the human species in vitro and in
      vivo.
AB  - Phenytoin therapy is a well recognized cause of gingival hyperplasia, a condition
      characterized by increased gingival collagen synthesis, and may also cause
      acromegalic-like facial features. Based on these clinical findings suggestive of
      anabolic actions, we sought to test the hypothesis that phenytoin acts on normal
      bone cells to induce osteogenic effects. To test the direct actions of phenytoin
      on human bone cells, we measured the dose responses to phenytoin for
      [3H]thymidine incorporation, cell number, alkaline phosphatase specific activity,
      and collagen synthesis in human hip bone-derived cells. Phenytoin significantly
      and reproducibly increased [3H]thymidine incorporation, cell number, alkaline
      phosphatase specific activity, and collagen synthesis in a biphasic manner with
      optimal stimulatory doses between 5-10 mumol/L. Thus, micromolar concentrations
      of phenytoin can act directly on human bone cells to stimulate osteoblast
      proliferation and differentiation. We next sought to test the hypothesis that
      phenytoin stimulates bone formation in humans in vivo. Accordingly, three serum
      biochemical markers of bone formation, i.e. osteocalcin, skeletal alkaline
      phosphatase, and procollagen C-terminal extension peptide, were measured in 39
      male epileptic patients, 20-60 yr of age, with an average duration of phenytoin
      therapy of 10.5 +/- 1.62 yr (mean +/- SEM). In this group of patients, the mean
      serum phenytoin level was 9.56 +/- 0.90 mg/L (mean +/- SEM; equivalent to 34.9 +/
      3.3 mumol/L). Thirty apparently healthy male subjects of similar age and taking
      no medication were included as controls. Serum calcium, 25-hydroxyvitamin D3, and
      PTH levels in the phenytoin-treated patients were not significantly different
      from those in the age-matched controls and were within the clinical laboratory
      normal range of our hospitals, indicating that the patients did not develop
      hypocalcemia, vitamin D deficiency, or secondary hyperparathyroidism. Serum
      levels of osteocalcin, skeletal alkaline phosphatase, and procollagen peptide in
      the phenytoin-treated patients were significantly increased compared to those in
      the age-matched subjects; in each case these biochemical markers were
      significantly correlated with the serum phenytoin level, but not with the dose or
      duration of phenytoin treatment. These findings are consistent with the
      interpretation that phenytoin increases the bone formation rate in humans in
      vivo.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7629229
TI  - Core body temperature and circadian rhythm of hot flashes in menopausal women.
AB  - Postmenopausal hot flashes are characterized by sweating and peripheral
      vasodilation and occur more frequently during increased heat loads. The circadian
      rhythm of core body temperature (TC) is well known and suggests that hot flashes
      will be most frequent when core temperature is highest. This hypothesis has not
      been tested previously. Ten symptomatic and six asymptomatic postmenopausal women
      were recruited from advertisements and screened. Each received 24-h ambulatory
      monitoring of sternal skin conductance levels to detect hot flashes, ambient
      temperature, skin temperature, and TC. The last measure was recorded using an
      ingested radiotelemetry pill. Cosinor analysis demonstrated a circadian rhythm (P
      < 0.02) of hot flashes with a peak at about 1825 h. TC values of the symptomatic
      women were lower than those of the asymptomatic women (P < .05) from 0000-0400 h
      and at 1500 and 2200 h. The majority of hot flashes were preceded by elevations
      in TC. Thus, elevated TC may serve as one trigger of menopausal hot flashes.

PMID- 7629230
TI  - Proinsulin immunoreactivity in identical twins discordant for noninsulin
      dependent diabetes mellitus.
AB  - Disproportionate elevation [increased proinsulin/insulin (PI/INS) ratio] of PI
      immunoreactivity is associated with noninsulin-dependent diabetes mellitus
      (NIDDM). The nature of this abnormality is not known. To address the question of
      whether genetic factors contribute to hyperproinsulinemia, we measured fasting
      levels of PI immunoreactivity, intact INS, and C peptide (CP) in 12 pairs of
      monozygotic twins discordant for NIDDM for a mean (+/- SEM) period of 9 +/- 3 yr.
      Thirteen age- and body mass index-matched healthy subjects without any family
      history of NIDDM acted as controls. The nondiabetic twins had levels of fasting
      INS, CP, PI, PI/CP, and PI/INS similar to those of control subjects. Fasting
      levels of PI, and PI/CP and PI/INS ratios were significantly 2- to 3-fold
      elevated in NIDDM twins compared to those in both nondiabetic twins and control
      subjects. To investigate whether hyperproinsulinemia in these NIDDM patients was
      due to a differential elevation of intact PI or conversion intermediates, we
      analyzed PI profiles in NIDDM twins and normal subjects by high pressure liquid
      chromatography. PI was heterogeneous and consisted mainly of des(31,32)-PI and
      intact PI in both NIDDM patients and normal subjects, with no major difference in
      composition between the groups. Small amounts of des(64,65)-PI (0-11%) were
      measured in some patients and normal subjects. The results suggest that
      hyperproinsulinemia is not a genetically determined trait per se in NIDDM.
      Disproportionately elevated PI levels seem to be related to the actual disease
      process. Further conversion of intact PI and des(31,32)-PI may be equally
      impaired in NIDDM.

PMID- 7629231
TI  - Impaired thyroxine and 3,5,3'-triiodothyronine handling by rat hepatocytes in the
      presence of serum of patients with nonthyroidal illness.
AB  - In systemic nonthyroidal illness (NTI), peripheral production of T3 from T4 is
      decreased, resulting in a decreased serum T3 concentration. We investigated
      whether factors in serum of NTI patients may play a role in this energy-saving
      adaptation mechanism. Metabolism of T4 and T3 by rat hepatocytes in primary
      culture was measured in the presence of 10% serum of normal subjects or of
      patients with NTI and related to the severity of disease. Patients with NTI were
      grouped according to serum thyroid hormone abnormalities: group I, serum rT3, T3,
      and T4 normal; group III, rT3 elevated, T3 decreased, T4 normal; group IV, rT3
      elevated, T3 and T4 decreased. Compared with metabolism in the presence of normal
      serum, metabolism of T4 and to a lesser extent of T3 was progressively decreased
      in the presence of serum of patients of groups I-IV. A decreased net deiodination
      of T4 and T3 (corrected for differences in free hormone concentration) without an
      increase in conjugated T4 and T3 (corrected for differences in free hormone
      concentration) was observed, similar to results in experiments with compounds
      inhibiting transport into the cells and not the metabolic processes (5'
      deiodination) per se. Deiodination of T4 in vitro was correlated with serum T3
      concentration of the patient (r = 0.69). Serum of patients with NTI influences
      thyroid hormone handling by hepatocytes comparable to the effect of transport
      inhibitors and not to that of the 5'-deiodinase inhibitor propylthiouracil,
      suggesting that decreased thyroid hormone transport over the cell membrane may
      play a role in lowered T3 production in NTI.

PMID- 7629232
TI  - Skeletal muscle proteolysis is reduced in noninsulin-dependent diabetes mellitus
      and is unaltered by euglycemic hyperinsulinemia or intensive insulin therapy.
AB  - To assess how noninsulin-dependent diabetes mellitus (NIDDM) and diabetes control
      may alter whole body and skeletal muscle proteolysis, we measured the rate of
      appearance (Ra) of phenylalanine (reflecting proteolysis) in the whole body and
      across the leg (reflecting skeletal muscle), using a constant tracer infusion of
      [2H5]phenylalanine in the basal state and during high-dose euglycemic
      hyperinsulinemia in 6 NIDDM and 10 control subjects. Studies were performed in
      NIDDM subjects 2 weeks after complete withdrawal of antidiabetic treatment and
      again after intensive insulin therapy. After intensive treatment, significant
      reductions were measured in hemoglobin A1C, fasting glucose concentrations, and
      basal hepatic glucose output. In contrast, there was no change after therapy in
      basal whole body or leg phenylalanine Ra. Compared with that of controls, whole
      body phenylalanine Ra was significantly higher and leg phenylalanine Ra
      significantly lower in NIDDM subjects. During euglycemic hyperinsulinemia, whole
      body phenylalanine Ra was significantly suppressed (approximately 15%) below
      basal values before and after therapy in NIDDM subjects and similarly suppressed
      in control subjects. However, in NIDDM subjects, euglycemic hyperinsulinemia did
      not reduce leg phenylalanine Ra below basal values either before or after
      therapy, whereas hyperinsulinemia resulted in a 42% suppression of leg
      phenylalanine Ra in controls. We conclude that 1) the clear improvement in
      glucose metabolism produced by intensive insulin therapy in NIDDM is not
      accompanied by changes in whole body or skeletal muscle proteolysis; 2) skeletal
      muscle proteolysis is reduced even though whole body proteolysis is increased in
      NIDDM subjects compared with controls; and 3) although a high-dose systemic
      infusion of insulin significantly reduces whole body proteolysis in both NIDDM
      and control subjects, skeletal muscle proteolysis is suppressed only in controls.
      We speculate that in NIDDM, high basal insulin concentrations (approximately 200
      pmol/L, unaltered by therapy) maximally suppress skeletal muscle proteolysis, and
      therefore higher insulin concentrations produce no additional suppression in
      skeletal muscle.

PMID- 7629233
TI  - Ad4BP in the human adrenal cortex and its disorders.
AB  - Ad4BP, a zinc finger DNA-binding protein, is a transcription factor that
      regulates the expression of the steroidogenic P450 genes. We performed
      immunoblotting and immunohistochemistry of Ad4BP in 34 human adrenal cortex
      specimens, which included adrenocortical adenomas and carcinomas. Immunoblotting
      revealed a single band of 53K, corresponding to the mol wt of Ad4BP. The
      immunohistochemical studies demonstrated that Ad4BP immunoreactivity was present
      exclusively in the nuclei of nearly all of the adrenocortical parenchymal cells
      in both the normal and the pathological human adrenal specimens. Ad4BP was
      immunostained with equal intensity and frequency among the different cell types.
      Ad4BP immunoreactivity was also observed in areas of marked degenerative changes,
      such as lipomyelomatous lesions, and in poorly differentiated carcinoma cells.
      These results suggest a close association of Ad4BP expression with the biological
      phenotype of adrenocortical parenchymal cells. Ad4BP therefore seems to play
      important roles in the induction and maintenance of the transcription of all
      steroidogenic P450 genes in human adrenocortical cells, even after malignant
      transformation.

PMID- 7629235
TI  - The human myometrium expresses multiple isoforms of the corticotropin-releasing
      hormone receptor.
AB  - Specific high affinity binding sites for CRH have been identified and
      characterized in the pituitary and central nervous system as well as in
      peripheral tissues. We recently identified and characterized a specific CRH
      receptor in human myometrium that changes to a high affinity state before term.
      In view of this, we searched for receptor heterogeneity in the pregnant and
      nonpregnant human myometrial CRH receptor. Myometrial membranes were prepared by
      differential centrifugation from either pregnant (cesarian section) or
      nonpregnant (hysterectomy) myometrium. Using a specific RRA followed by
      isoelectric focusing and autoradiography, multiple isoforms of the human
      myometrial CRH receptor were identified that were identical in both pregnant and
      nonpregnant myometrium. Five isoforms were identified (pI 4.65, 4.8, 4.95, 5.1,
      and 5.2). Reduction of disulfide bridges with reducing agents (dithiothreitol and
      cysteine) increased the specific binding of CRH to its myometrial receptor, and
      the action of dithiothreitol affected the two most basic receptor isoforms. These
      results suggest the presence of multiple isoforms of CRH receptors that may have
      different properties and functions and the presence of disulfide bridges within
      the myometrial CRH receptor, which are important, but not critical, for the
      receptor binding.

PMID- 7629234
TI  - Identification of human growth hormone-releasing hormone receptor splicing
      variants.
AB  - The expression pattern of the receptor for human GHRH (hGHRHr) was investigated
      in normal human tissues and in pituitary and ovarian tumors by reverse
      transcription-polymerase chain reaction. Three transcriptional variant forms of
      the hGHRHr were found to be expressed in the normal pituitary and in GH-secreting
      pituitary tumors. Form a is identical to the previously reported hGHRHr, whereas
      forms b and c are not described in the literature. Form b and c are predicted to
      be transcribed into two truncated proteins. We amplified genomic DNA using
      primers designed from the complementary DNA of hGHRHr. A 2-kilobase genomic DNA
      fragment was cloned that contains part of the hGHRHr gene consisting of two
      exons, e864 and e934, separated by three introns, i863, i933, and i1025.
      Alternative splicing of i1025 was responsible for three variant forms of hGHRHr.
      Nonsecreting pituitary tumors showed an abnormal expression of the hGHRHr,
      probably due to alternative usage of exons at the 5'-end of the gene, although
      they also expressed the three variant forms. No hGHRHr expression was identified
      in a human mammosomatotroph cell line insensitive to GHRH, in normal human liver
      or ovary, or in various human ovarian tumors.

PMID- 7629236
TI  - Testicular steroidogenesis in adult men with human chorionic gonadotropin
      producing tumors.
AB  - There are few critical studies on plasma testosterone (T) and 17 beta-estradiol
      (E2) levels in men with hCG-producing tumors, and the results are contradictory.
      Plasma E2 levels are most often elevated, whereas plasma T values are high or in
      the normal range. We studied the plasma levels of such steroids and of delta 4
      and delta 5 T precursors in adult men with intact hCG-producing tumors to
      evaluate the relationship between hCG and steroid hormone levels or steroidogenic
      enzyme activities. Ten adult men with hCG-producing tumors and 25 normal adult
      men were investigated. Seven men with testicular tumors were studied before and
      after hemicastration. The 2 patients with extratesticular tumors were
      investigated before and during chemotherapy. The remaining patient was studied
      every 2 months for 1 yr during the spontaneous course of the disease. Plasma
      progesterone (P), 17 alpha-hydroxyprogesterone (17-OHP), androstenedione (A), 17
      hydroxy-delta 5-pregnenolone (17-OH delta 5-P), dehydroepiandrosterone (DHEA), T,
      E2, and hCG were measured, and ratios of steroid levels were also calculated. In
      patients with increased hCG values (i.e. > 5 IU/L), the mean plasma P, 17-OHP, A,
      17-OH delta 5-P, DHEA, T, and E2 levels were higher (P < 0.01 at least) than
      those in patients whose hCG values were normalized or in controls. The patterns
      of these steroids were very different according to plasma hCG levels. Indeed, for
      hCG levels between more than 5 and 3.5 x 10(3) IU/L, positive correlations (P <
      0.05 at least) were found between hCG levels and delta 4 T precursor, delta 5 T
      precursor, T, or E2 values. Conversely, for hCG values greater than 3.5 x 10(3)
      IU/L, hCG levels were negatively correlated (P < 0.05 at least) to all steroid
      values. Furthermore, in patients with increased hCG levels, the mean plasma P to
      17-OHP ratio, 17-OHP to A ratio, A to T ratio, 17-OHP to T ratio, and 17-OH delta
      5-P to DHEA ratio were similar to those in patients with normalized hCG values or
      in controls. In contrast, in patients with increased hCG levels, the mean plasma
      T to E2 ratio value was lower (P < 0.001) than that in patients with normalized
      hCG levels or in controls.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7629237
TI  - Circulating factors and insulin resistance. I. A novel myoinositol 1,2-cyclic
      phosphate phosphoglycan insulin antagonist from human plasma is elevated in
      noninsulin-dependent diabetes mellitus.
AB  - A novel low mol wt inositol phosphoglycan inhibitor (M tau 1200-1500) of insulin
      action in rat adipocytes has been partially purified from normal human plasma.
      This inhibitor, termed fraction V after the first purification step and fraction
      V3 after the second, is different from other reported serum insulin antagonists.
      It contains myoinositol, galactosamine, and mannose in approximate molar ratios
      of 1:1:3.3. The myoinositol has a 1,2-cyclic phosphate substituent, which is
      essential for the inhibitory activity. Its inhibitory activity is significantly
      elevated (161%, P < 0.05 for fraction V; 278%, P < 0.05 for fraction V3) in
      plasma of humans with noninsulin-dependent diabetes mellitus as compared with
      plasma of nondiabetic controls. These findings represent the first report of a
      naturally occurring mammalian inositol 1,2-cyclic phosphate containing
      phosphoglycan related to insulin action.

PMID- 7629238
TI  - Elevated levels of adrenocorticotropin (ACTH) precursors in post-adrenalectomy
      Cushing's disease and their regulation by glucocorticoids.
AB  - The ACTH precursor pro-opiomelanocortin (POMC) undergoes specific endoproteolytic
      cleavages in the anterior pituitary gland to give ACTH-(1-39). ACTH precursors
      circulate in normal subjects and are high both in the ectopic ACTH syndrome and
      in patients with aggressive pituitary adenomas. This study examines plasma levels
      of ACTH precursors and ACTH in 24 patients with post-adrenalectomy Cushing's
      disease, in 10 of whom computed tomography showed evidence of tumor progression.
      ACTH precursors were higher in post-adrenalectomy Cushing's disease (median 97.5
      pmol/L, range 26-647 pmol/L) than in untreated Cushing's disease (median 29
      pmol/L, range 9-104 pmol/L) and normal controls (5-40 pmol/L) (P < 0.001) and
      were significantly higher in patients with larger tumors (median 175 pmol/L,
      range 52-647 pmol/L) than in the remainder (median 41 pmol/L, range 26-510
      pmol/L) (P = 0.02). Surprisingly, pro-opiomelanocortin (POMC) processing to ACTH
      was enhanced in post-adrenalectomy patients (ratio 1 +/- 0.5) compared with
      Cushing's disease (5.6 +/- 0.8) and normal subjects (5.3 +/- 0.9). After
      hydrocortisone ACTH precursors rose in 36% of post-adrenalectomy patients
      (increase 15-78%) and remained within 10% of basal levels in 46%. Six patients
      had a rise in precursors and a fall in ACTH suggesting differential regulation of
      these peptides. In conclusion, whereas ACTH precursors are high in post
      adrenalectomy Cushing's disease and higher levels correlate with tumor
      progression, processing of precursors to ACTH is enhanced.

PMID- 7629239
TI  - Mechanisms of enhanced insulin sensitivity in endurance-trained athletes: effects
      on blood flow and differential expression of GLUT 4 in skeletal muscles.
AB  - Exercise is associated with increased insulin sensitivity. To better understand
      mechanisms that could be responsible for this association, we studied seven
      controls and seven endurance-trained athletes. A 600 mU/m2.min hyperinsulinemic
      euglycemic glucose clamp with the limb balance technique assessed insulin
      sensitivity as whole body glucose uptake (WBGU) and leg glucose uptake (LGU).
      Indirect calorimetry and hemodynamic measurements, such as leg blood flow (LBF)
      and cardiac output, were performed at baseline and maximal insulin stimulation.
      The content of the glucose transporter GLUT 4 and muscle fiber type were
      evaluated in three muscle groups: vastus lateralis, gastrocnemius, and biceps.
      Athletes exhibited 35% higher WBGU and 30% higher LGU than controls. Basal LBF
      (liters per min) was higher in athletes, but the difference was not statistically
      significant. After insulin stimulation, LBF was 31% higher in athletes than
      controls (P = 0.05). Indirect calorimetry revealed that athletes had a 44% higher
      rate of nonoxidative glucose metabolism than controls (P = 0.01). GLUT 4 levels
      in vastus were 90% (P < 0.05) greater in athletes, whereas smaller differences
      were noted between athletes and controls in biceps and gastrocnemius.
      Importantly, the vastus lateralis GLUT 4 content was correlated with WBGU (r =
      0.60; P < 0.05) and LGU (r = 0.62; P < 0.05). Relative numbers of oxidative
      fibers were increased in vastus from athletes and were positively correlated with
      maximal oxygen consumption (VO2 max), but GLUT 4 content could not be correlated
      with oxidative fiber content in individual controls or athletes. We conclude that
      in humans 1) endurance training enhances insulin's ability to increase LBF; 2)
      GLUT 4 is differentially expressed as a function of muscle group and is up
      regulated by exercise in a muscle-specific manner; 3) in vastus lateralis, GLUT 4
      levels are well correlated with insulin-stimulated rates of both WBGU and LGU;
      and 4) GLUT 4 content and in vivo insulin sensitivity do not vary as a function
      of fiber type composition. Thus, blood flow and GLUT 4 expression in muscle are
      important mechanisms that mediate greater insulin sensitivity in athletes.

PMID- 7629240
TI  - Comparison of markers for bone formation and resorption in premenopausal and
      postmenopausal subjects, and osteoporosis patients.
AB  - Recently, the biochemical markers for bone metabolism have been developed and are
      expected to reflect the minor change of bone turnover. We compared bone formation
      markers: alkaline phosphatase-(Alp), bone gla-protein(BGP), carboxy-terminal
      propeptide of type I collagen(PICP); and bone resorption markers: carboxy
      terminal telopeptide of type I collagen(ICTP), pyridinoline(Pyr),
      deoxypyridinoline(Dpyr) to see if they reflected the effects of aging and
      menopause in 95 premenopausal and 66 postmenopausal healthy subjects. We also
      compared the bone turnover in 29 vertebral osteoporosis patients. All markers
      except ICTP significantly increased with age in the healthy subjects. Alp, BGP,
      PICP, Pyr, and Dpyr were significantly higher in the postmenopausal group than in
      the premenopausal group. BGP, Pyr, and Dpyr in premenopausal subjects in their
      50s were already significantly increased compared with BGP, Pyr, and Dpyr in
      premenopausal subjects in their 30s and 40s. To evaluate the discrimination power
      of the six markers in the postmenopausal subjects and in patients with
      osteoporosis, the z scores of six markers were calculated against the
      premenopausal group. z-scores of bone resorption markers(ICTP, Pyr, and Dpyr)
      were much higher than those of bone formation markers (Alp, BGP, and PICP) in
      patients with osteoporosis, even though z-scores of bone resorption markers were
      similar to those of bone formation markers in postmenopausal subjects. In
      conclusion, Alp, BGP, PICP, Pyr, and Dpyr had good performance in postmenopausal
      status. Resorption markers increased more than formation markers in osteoporosis
      subjects, and the bone turnover in osteoporosis subjects was more uncoupled than
      in postmenopausal subjects.

PMID- 7629241
TI  - Receptors for pituitary adenylate cyclase-activating peptide in human liver.
AB  - The presence as well as the pharmacological, molecular, and functional properties
      of pituitary adenylate cyclase-activating peptide (PACAP) receptors have been
      analyzed in human liver membranes compared in parallel with vasoactive intestinal
      peptide (VIP) receptors. [125I]PACAP-27 bound to two classes of receptors with
      high [dissociation constant (Kd) = 0.47 nmol/L] and low (Kd = 8.0 nmol/L)
      affinities that represented about 34% and 66% of total binding sites,
      respectively. The pharmacological profile of [125I]VIP and [125I]PACAP-27 binding
      to membranes supported the coexistence with VIP receptors of specific receptors
      for PACAP with a mol wt equal to 67.7K. When [125I]PACAP-27 was used, the order
      of potency of various related peptides for competition of tracer binding was
      PACAP-27 greater than PACAP-38 greater than VIP. Both PACAP-27 and VIP stimulated
      adenylate cyclase activity with similar efficacy, although PACAP-27 showed a
      potency (half-maximal efficient concentration or EC50 = 0.5 nmol/L) greater than
      that of VIP (EC50 = 4.1 nmol/L). When the two peptides were present
      simultaneously in the incubation medium, no additive effect on the stimulation of
      adenylate cyclase activity was observed, which suggests a unique receptor coupled
      to this enzyme.

PMID- 7629242
TI  - The dissociation of catecholamine and hypothalamic-pituitary-adrenal responses to
      daily stressors using dexamethasone.
AB  - The hypothalamic-pituitary-adrenal (HPA) and sympathetic-adrenal-medullary (SAM)
      systems are implicated in the human stress response. One characterization of
      these systems is that they are nonspecific in their response, but differ in
      activation threshold and time course. Additionally, they have been found to be
      affected commonly by strong metabolic stressors and infusions of CRH, and a
      hypothesis has been developed primarily from animal research that CRH stimulates
      both the HPA and SAM systems. To determine whether CRH was significantly involved
      in tonic as well as psychological stress-induced catecholamine levels in man, we
      infused 24 normal male undergraduate students with either saline (n = 12) or
      dexamethasone (DEX; n = 12) and evaluated their subsequent plasma levels of ACTH,
      cortisol, epinephrine (EPI), and not epinephrine (NEPI). DEX produced a dramatic
      decrease in ACTH and cortisol levels, but no significant changes in EPI or NEPI
      occurred over a 4-h sampling interval. After the administration of math and
      speech stressors in a controlled laboratory setting, DEX inhibited the ACTH and
      cortisol release that was noted in the saline group, but stress-induced increases
      in EPI and NEPI were comparable in both groups. Thus, our study suggests that
      there is a difference in the neural pathways for tonic and stress-induced
      stimulation of the SAM and HPA systems.

PMID- 7629243
TI  - Contribution of obesity to insulin resistance in noninsulin-dependent diabetes
      mellitus.
AB  - Inasmuch as previous studies have obtained conflicting results on the
      contribution of obesity to insulin resistance in noninsulin-dependent diabetes
      mellitus (NIDDM), we studied 10 nonobese and 10 obese NIDDM patients with the
      isoglycemic-(approximately 10 mmol/L)-hyperinsulinemic clamp (two insulin
      infusions of 4 and 40 mU/m-2 min-1), combined with [3-3H]glucose infusion and
      indirect calorimetry. As compared with nonobese patients, obese NIDDM patients
      had higher baseline peripheral and estimated portal plasma insulin concentrations
      (113 +/- 18 vs. 46 +/- 3 pmol/L and 288 +/- 53 vs. 98 +/- 6 pmol/L, respectively;
      P < 0.05) and less suppressed endogenous insulin production during clamp. Hepatic
      glucose production was greater in obese than in nonobese patients (basal, 16 +/-
      1.1 vs. 12 +/- 0.5 mumol/kg-1 fat-free mass (FFM) min-1; clamp, 5.7 +/- 0.5 vs.
      2.8 +/- 0.2 mumol/kg-1 FFM min-1, P < 0.05). Glucose utilization increased to a
      lesser extent in obese than in nonobese patients (49 +/- 5 vs. 73 +/- 7 mumol/kg
      1 FFM min-1, P < 0.05) during clamp because of a lower increase in nonoxidative
      glucose metabolism (30 +/- 5 vs. 50 +/- 7 mumol/kg-1 FFM min-1, P < 0.05). Plasma
      free fatty acid concentrations and rates of lipid oxidation were greater in obese
      (P < 0.05) patients and correlated with hepatic glucose production (r = 0.79 and
      0.50, P < 0.05). In conclusion, obesity exaggerates hepatic as well as extra
      hepatic insulin resistance in NIDDM. The impaired inhibition of pancreatic beta
      cell function by exogenous insulin contributes to exaggerated hyperinsulinemia in
      obese NIDDM.

PMID- 7629246
TI  - There is no difference in spontaneous and 17 beta-estradiol-induced interleukin-1
      beta release by peripheral blood mononuclear cells from nonosteoporotic women
      with different rates of early postmenopausal bone loss.
AB  - Interleukin-1 (IL-1) is a potent stimulator of bone resorption, and a causal role
      for IL-1 has been suggested in postmenopausal bone loss. We have examined IL-1
      beta release in vitro by peripheral blood mononuclear cells (PBMC) isolated from
      nonosteoporotic women 9-15 yr after menopause. These women had presented 6 yr
      previously with significant differences in the rate of early postmenopausal bone
      loss. Ten women with low rates of bone loss (median 2.0% per year) and 10 women
      with high rates of bone loss (median 4.9% per year) were included in the study.
      The women with a high rate of bone loss had a significantly lower bone mass of
      the lumbar vertebrae compared with that of the other group, but there were no
      differences in biochemical markers of bone metabolism between the groups
      (pyridinoline/creatinine ratio in urine and collagen 1 c-terminal telopeptide and
      bone gla protein in serum). Moreover, there was no difference in spontaneous IL-1
      beta release by PBMCs between the two groups and no correlation between IL-1 beta
      release and present bone turnover, as judged by biochemical markers. Treatment of
      PBMCs with 10 nmol/L 17 beta-estradiol in vitro significantly stimulated IL-1
      beta production in both groups. We conclude that IL-1 beta production by PBMCs in
      vitro does not correlate with the rate of early postmenopausal bone loss.

PMID- 7629245
TI  - Long term follow-up of transsphenoidal surgery for the treatment of Cushing's
      disease in childhood.
AB  - Transsphenoidal removal of pituitary adenomas has become the accepted treatment
      for Cushing's disease. As Cushing's disease is rare in childhood, few reports
      describe extended follow-up after transsphenoidal surgery for this disease in
      children. Twenty-two patients less than 19 yr of age were diagnosed with
      Cushing's disease by standard testing. All patients underwent transsphenoidal
      surgery (TSS) as primary treatment at Mayo Clinic between 1975 and 1990. Follow
      up was available in all patients and averaged 6.7 yr. Adenomas were identified
      pathologically in 19 patients and visualized by the surgeon in the remainder.
      There was 1 macroadenoma. Ten patients are considered cured with a mean follow-up
      of 5.5 yr. Five patients had evidence of persistent disease within 6 months of
      TSS and required further treatment. Seven patients had remission lasting greater
      than 6 months with subsequent relapse (mean time to recurrence, 7.0 yr). In
      children treated with TSS for Cushing's disease, the rate of cure with extended
      follow-up is only approximately 50%. This rate is much lower than that in adults
      and may indicate that Cushing's disease is more aggressive in childhood. As TSS
      is associated with low morbidity, we feel it is still the treatment of choice for
      Cushing's disease in children.

PMID- 7629244
TI  - Methimazole has no dose-related effect on the intensity of the intrathyroidal
      autoimmune process in relapsing Graves' disease.
AB  - Declining thyroid autoantibodies during treatment and decreased lymphocytic
      infiltration after treatment of patients with Graves' disease suggest
      immunosuppressive actions of antithyroid drugs. However, the recent report of
      similar relapse rates after low and high dose carbimazole treatment of Graves'
      disease seems to contradict the immunosuppression thesis. We therefore determined
      the intrathyroidal methimazole concentrations with a high performance liquid
      chromatography method in 17 patients undergoing subtotal thyroid resection for
      relapsing Graves' disease. The intensity of the intrathyroidal infiltration by
      immunoglobulin G-producing plasma cells, activated T cells, and antigen
      presenting cells, and the total number of lymphocytes were identified
      immunohistologically with monoclonal antibodies for kappa- and lambda
      immunoglobulin light chains, UCHL1, and the S100 antibody, respectively, followed
      by morphometry. The intrathyroidal methimazole concentration and the cumulative
      preoperative methimazole doses did not correlate with the intensity of the
      intrathyroidal infiltration by any of these immunocompetent cells. Comparison of
      groups with significantly different intrathyroidal methimazole concentrations
      (134 ng/g, n = 8 vs. 993 ng/g, n = 7) showed no significant differences for any
      of the intrathyroidal immunocompetent cells. These findings suggest that there is
      no dose-related effect of methimazole on the intensity of the intrathyroidal
      autoimmune process of patients with relapsing Graves' disease. They provide an
      explanation for why it does not seem justifiable to recommend higher methimazole
      doses than those required for the control of hyperthyroidism with the goal of
      immunosuppression.

PMID- 7629247
TI  - Selective venous sampling from the cavernous sinuses is not a more reliable
      technique than sampling from the inferior petrosal sinuses in Cushing's syndrome.
AB  - The purpose of this study was to compare ACTH levels in unstimulated samples
      obtained from the cavernous sinuses (CS) to unstimulated and CRH-stimulated
      samples obtained from the inferior petrosal sinuses (IPS) in 15 patients with
      surgically proven Cushing's disease. After unstimulated samples were obtained
      through 5-French catheters placed in both IPS, tracker catheters were introduced
      into both cavernous sinuses, and unstimulated samples were obtained within 5 min
      of the initial set. The Tracker catheters were removed, CRH was administered, and
      CRH-stimulated samples were obtained from the IPS. We compared the central to
      peripheral ACTH ratios in unstimulated samples from the cavernous sinuses to
      unstimulated and CRH-stimulated samples from the IPS as a basis for
      distinguishing pituitary from ectopic ACTH production. In addition, we compared
      the ability of the intercavernous and interpetrosal ACTH ratios to correctly
      predict the site of the microadenoma. Unstimulated levels of ACTH in the
      cavernous sinuses were generally higher than unstimulated levels of ACTH in the
      petrosal sinuses. However, 3 of 15 patients failed to show central to peripheral
      ACTH ratios greater than 2 in unstimulated samples from the cavernous sinuses and
      were thus falsely negative for the diagnosis of Cushing's disease (test
      sensitivity, 80%). By comparison, the test sensitivity for the petrosal sinus
      samples was 87% for the unstimulated samples and 100% for the CRH-stimulated
      samples. Lateralization was correct in 6 of 15 patients based on CS samples and
      in 9 of 15 patients based on IPS samples. Because of the 20% false negative rate,
      CS sampling without CRH stimulation is not recommended for the differential
      diagnosis of ACTH-dependent hypercortisolism.

PMID- 7629248
TI  - A novel mutation of the luteinizing hormone receptor gene causing male
      gonadotropin-independent precocious puberty.
AB  - Familial male-limited precocious puberty (FMPP) is an autosomal dominant
      gonadotropin-independent disorder. Affected males generally develop signs of
      precocious puberty in early childhood. They typically show Leydig cell
      hyperplasia and increased testosterone production typical for their age, whereas
      circulating LH concentrations remain prepubertal. Several dominant point
      mutations of the LH receptor gene were identified in pedigrees with familial male
      limited precocious puberty and were shown to cosegregate with the disease. Here
      we report a novel heterozygote point mutation in the LH receptor gene of a
      Brazilian boy with gonadotropin-independent precocious puberty. This mutation
      substitutes alanine 568 with valine at the carboxyterminus of the third cytosolic
      loop of the LH receptor. The unoccupied mutant receptors confer constitutive
      activation of adenyl cyclase activity when expressed in COS-7 cells, resulting in
      4-fold higher cAMP concentrations over baseline compared with cells expressing an
      equivalent number of wild-type receptors. The affinity of the mutant receptors to
      125I-labeled human LH was not altered compared with the wild type. Mutations of
      the homologue alanine residue in the alpha 1-adrenergic (in vitro), FSH (in
      vitro), and TSH (naturally occurring) receptors also result in constitutive
      adenyl cyclase activation, suggesting that this alanine residue is crucial for
      signal transduction and a potential site for upregulatory/oncogenic mutations in
      G-protein coupled receptors.

PMID- 7629249
TI  - Acipimox potentiates growth hormone (GH) response to GH-releasing hormone with or
      without pyridostigmine by lowering serum free fatty acid in normal and obese
      subjects.
AB  - Obesity is associated with an impairment of normal GH secretion and blunted
      responses to all stimuli. Recent reports suggest that increased somatostatinergic
      activity is the basis for the GH derangement of obesity. However, the basic
      mechanism of this alteration is still being debated. The high plasma free fatty
      acid (FFA) is frequently observed in obesity. FFA participates in the regulation
      of pituitary GH secretion. To determine whether the derangement of GH secretion
      in obesity is associated with high plasma FFA levels, several tests with GHRH
      with or without pyridostigmine (PYR) and acipimox (ACX), antilipolytic agents
      able to decrease FFA, were undertaken in six obese and seven normal control
      subjects. In obese subjects, the GH response (mean peak +/- SEM: 8.9 +/- 1.1
      ug/L) to GHRH-(1-29) (1 ug/kg, i.v.) was significantly blunted when compared with
      the response in normal control subjects (25.7 +/- 1.8 ug/L; P < 0.05). After PYR
      (120 mg), the response to GHRH was enhanced in the obese subjects (21.4 +/- 4.9
      ug/L; P < 0.05) and was similar to that of the controls with GHRH only, but
      remained significantly reduced compared with controls treated with PYR plus GHRH
      (43.2 +/- 6.0 ug/L; P < 0.05). Basal FFA levels were higher than those of normal
      controls (P < 0.05). ACX (500 mg) decreased FFA levels in both obese and normal
      subjects; the lowest FFA levels of obese subjects at 15 min were similar to those
      of normal controls. ACX also potentiated GHRH-stimulated GH response in both
      obese and normal subjects. The GH responses potentiated by ACX in obesity (22.7
      +/- 5.5 ug/L) were similar to those of PYR plus GHRH in obese subjects and GHRH
      in normal controls, but they were lower than those of control treated with ACX
      plus GHRH (50.8 +/- 6.7 ug/L; P < 0.05). After the combined pretreatment with ACX
      and PYR, GH responses in obesity (44.1 +/- 6.0 ug/L) were significantly higher
      than those in GHRH test, PYR plus GHRH, and ACX plus GHRH in obese subjects (P <
      0.05), and they were similar to PYR plus GHRH or ACX plus GHRH in normal
      controls. However their enhanced GH responses were reduced compared with the
      control with ACX plus PYR plus GHRH (64.9 +/- 4.5 ug/L; P < 0.05). Our results
      are in agreement with the hypothalamic hypothesis: an increase in
      somatostatinergic tone is responsible for the blunted GH response to GHRH in
      obesity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7629250
TI  - Effect of heavy alcohol intake in the absence of liver disease on bone mass in
      black and white men.
AB  - Previous studies have shown that bone mass is significantly decreased in chronic
      alcoholic white patients, especially those with evidence of liver involvement.
      However, liver disease is an independent risk factor for bone loss. In vitro
      studies have shown that alcohol has a direct effect on osteoblasts. The effects
      of chronic alcohol consumption on bone mass in the absence of liver disease are
      not known. In addition, the effect of alcohol on bone in black alcoholic subjects
      has not been examined previously. In the present study, we evaluated the effects
      of prolonged heavy alcohol intake on bone mass in both black (n = 21) and white
      (n = 19) male subjects without significant liver disease. Bone mineral density
      (BMD) of the lumbar spine and hip and various markers of bone metabolism in
      alcoholic subjects were compared with those in respective age-matched controls (n
      = 16 blacks and 14 whites). Mean values for BMD of the lumbar spine, total hip,
      and femoral neck were not significantly different between alcoholic subjects and
      their respective controls among either blacks or whites. In white subjects, age
      and duration of alcohol were noted to have significant independent effects on
      BMD, whereas in blacks, age was the only factor that significantly affected bone
      mass independently. In the absence of liver disease, prolonged heavy alcohol
      intake results in bone loss in white subjects. The skeleton of black subjects may
      be less affected by alcohol.

PMID- 7629251
TI  - Plasminogen activator activity during decidualization of human endometrial
      stromal cells is regulated by plasminogen activator inhibitor 1.
AB  - Progesterone acts on the estradiol (E2)-conditioned human endometrium to induce
      decidualization of stromal cells. Consistent with these differential hormone
      actions in vivo, progestins regulate several end points of decidualization in
      human endometrial stromal cell monolayers, and E2 augments the effects of
      progestin. This study shows that in vitro decidualization of the stromal cells is
      accompanied by diminished plasminogen activator (PA) expression. Polyacrylamide
      gel electrophoretic separation after immunoprecipitation of biosynthetically
      labeled PAs revealed that medroxyprogesterone acetate (MPA) lowered levels of
      secreted tissue type PA (tPA) at 67 kilodaltons and urokinase type PA (uPA) at 55
      kilodaltons. These levels were reduced further by E2 plus MPA despite a lack of
      response to E2 alone. Although tPA activity was readily measured by a chromogenic
      assay, detection of uPA activity required prior activation, indicating that uPA
      is released as the pro-uPA zymogen. Comparisons of levels of immunogenic PAs, as
      measured by specific enzyme-linked immunosorbent assays, with the corresponding
      catalytic activities revealed selective progestational inhibition of PA activity
      vs. antigen after 3 days of experimental incubation. Thus, 10(-7) mol/L MPA
      produced about a 2-fold greater reduction of levels of PA activity than that of
      its corresponding antigen. More strikingly, 10(-8) mol/L E2 plus 10(-7) mol/L MPA
      virtually eliminated both tPA activity (99% inhibition; P < 0.005) and uPA
      activity (93% inhibition; P < 0.005); the reductions in levels of the
      corresponding antigens were only about 50% of the control levels and did not
      attain statistical significance. Only after 3-6 days of incubation with E2 plus
      MPA was statistically significant inhibition achieved for immunogenic levels of
      both tPA (P < 0.05) and uPA (P < 0.005). Preferential inhibition of levels of PA
      activities compared with those of the corresponding PA antigens reflects the
      action of the potent PA inhibitor PAI-1. Thus, the concentration of PAI-1 in the
      stromal cell-conditioned medium at the end of 0-3 days exceeded those of tPA and
      uPA, respectively, by 28- and 12-fold in response to MPA and by 52- and 25-fold
      in response to E2 plus MPA. Extrapolation of these in vitro results to the events
      of the luteal phase, whose steroidal milieu is mimicked by E2 plus MPA, indicates
      that decidual cell-derived PAI-1 is a key regulator of proteolytic degradation of
      extracellular matrix and fibrinolysis during implantation and menstruation.

PMID- 7629252
TI  - Human bone cell phenotypes differ depending on their skeletal site of origin.
AB  - This report describes skeletal site-related differences in human osteoblastic
      cell metabolism in studies of four patients. Northern analyses of the
      constitutive growth factor messenger ribonucleic acid (mRNA) expression pattern
      in mandibular and iliac crest-derived human osteoblastic cells (based on within
      patient comparisons) revealed higher mRNA levels for strong mitogenic growth
      factors such as basic fibroblast growth factor (bFGF) and insulin-like growth
      factor II (IGF-II) in the rapidly proliferating and less alkaline phosphatase
      (ALP)-expressing mandibular osteoblastic cells compared to those in the lower
      bFGF and IGF-II mRNA levels in slowly proliferating iliac human osteoblastic
      cells exhibiting a higher ALP expression level. In contrast, transforming growth
      factor-beta (TGF beta) mRNA was more abundant in iliac human osteoblastic cells
      than in mandibular osteoblastic cells. Furthermore, we found that there was a
      proportionality, based on data from both sites, between the level of constitutive
      TGF beta mRNA and the response to exogenously administered bFGF or IGF-II. A
      comparable pattern of growth characteristics and mRNA expression was also
      observed in transformed human osteoblastic cells that had been subcloned in
      sublines expressing high and low levels of the human osteoblastic differentiation
      marker ALP. These findings are consistent with 1) skeletal site-related
      differences in human bone cell phenotypes, and 2) decreased IGF-II and bFGF
      expression and increased TGF beta expression and responsiveness to bFGF and IGF
      II in human bone cells exhibiting a high ALP expression.

PMID- 7629253
TI  - In vivo visualization of pituitary dopaminergic receptors by iodine-123
      methoxybenzamide (IBZM) correlates with sensitivity to dopamine agonists in two
      patients with macroprolactinomas.
AB  - We performed in two patients with macroprolactinoma, pituitary scintigraphy with
      123 iodine-methoxybenzamide (IBZM), a dopaminergic antagonist that specifically
      binds to the D2 dopaminergic receptors. In a 34-yr-old woman with basal PRL
      levels of about 2000 ng/mL, 7.5 mg/day of Bromocriptine (Br) for a month neither
      reduced PRL levels nor affected tumor size; in this patient single photon
      emission tomography SPECT failed to show any pituitary accumulation of the
      tracer. In the other patient, a 27-yr-old man presenting with cerebrospinal fluid
      rhinorrhea, basal PRL levels were at 5000 ng/mL; magnetic resonance imaging (MRI)
      demonstrated a huge pituitary tumor, and SPECT showed a very intense
      concentration of IBZM at the level of the adenoma. PRL levels fell dramatically
      to 530 ng/mL with only 2.5 mg/day of Br after 4 days; after 6 days with 7.5
      mg/day Br, PRL levels were 63 ng/mL, and the patient underwent surgery to correct
      cerebrospinal fluid leakage. We conclude that, in these two patients, the
      pituitary scintigraphy with IBZM has given information on the density of dopamine
      receptors on the adenoma and has correlated with the inhibitory effect of Br on
      PRL secretion. Whether this tool might be of value in identifying patients with
      pituitary tumors potentially responsive to Br treatment is still to be
      investigated.

PMID- 7629254
TI  - Seventeen alpha-hydroxylase deficiency with one base pair deletion of the
      cytochrome P450c17 (CYP17) gene.
AB  - Mutation of the cytochrome P450c17 (CYP17) gene causes 17 alpha-hydroxylase
      deficiency (17OHD). Recently, several researchers have elucidated the molecular
      basis of 17OHD by gene analysis. We experienced a case of 17OHD and intended to
      reveal the abnormality of the CYP17 gene in this Japanese female with 17OHD.
      Leukocytes were obtained from the patient, her mother and sister, and normal
      control subjects. We amplified the CYP17 gene using polymerase chain reaction and
      performed the sequence analysis using the dideoxy terminator method and
      restriction enzyme analysis. We found that the patient had one base-pair deletion
      at the position of amino acid 438. An identical result was obtained with
      restriction enzyme analysis. This G deletion altered the reading frame and
      resulted in a premature stop codon at position 443; the ligand of heme iron (Cys:
      cystine 442) was absent. This small mutation may account for the patient's
      clinical manifestations of 17OHD. This is the first case of 17OHD with only one
      base pair deletion of the CYP17 gene.

PMID- 7629255
TI  - Endogenous catecholamines suppress thyrotropin secretion during the early
      follicular phase of the menstrual cycle.
AB  - The physiological role of hypothalamic catecholamines in the regulation of TSH
      secretion in humans has not been studied extensively. We administered the
      catecholamine synthesis inhibitor alpha-methyl-p-tyrosine (AMPT) to five women in
      the early follicular phase (one of menstrual cycle days 2-5) of the menstrual
      cycle and compared TSH secretion patterns to those in five women at the same time
      in the cycle who did not receive AMPT. From 0800-1600 h, volunteers had an i.v.
      line placed, through which blood was withdrawn every 15 min for TSH and PRL
      determinations. AMPT (500 mg) was administered to the study group at 0800 h and
      again at 1000 h. Baseline TSH concentrations at 0800 h were not significantly
      different between the control and treatment groups. In keeping with its
      characteristic circadian secretion pattern, TSH in the control group was 1.72 +/-
      0.23 mIU/L at 0800 h, declined to 1.02 +/- 0.11 mIU/L by 1600 h, and was
      significantly less than the 0800 h value at all time points beyond 1115 h. The
      decline in TSH was observed in all five controls. By contrast, TSH in the AMPT
      group rose from an 0800 h value of 1.99 +/- 0.09 mIU/L to a peak of 3.30 +/- 0.86
      IU/L by 1245 h, and was significantly higher than that at 0800 h in the treated
      group from 1130-1315 h. The increase in TSH was observed in all five women who
      received AMPT. There were significant differences between the mean TSH
      concentrations in the AMPT-treated (2.51 +/- 0.09 mIU/L) vs. the control group
      (1.28 +/- 0.09 mIU/L; P < 0.0001) for the entire study. The effectiveness of AMPT
      was demonstrated by an elevation of mean PRL concentrations from a baseline of
      16.67 +/- 2.55 micrograms/L to a peak of 138.7 +/- 21.6 micrograms/L. We conclude
      that endogenous catecholamines tonically inhibit TSH secretion in the early
      follicular phase. These data suggest modulation of TRH by tuberoinfundibular
      dopamine at the hypothalamic and/or pituitary level.

PMID- 7629256
TI  - Macroorchidism in juvenile hypothyroidism.

PMID- 7629257
TI  - Citation for the 1995 Fred Conrad Koch Award of the Endocrine Society to Jack
      Gorski.

PMID- 7629258
TI  - Citation for the 1995 Edwin B. Astwood Lecture Award to Kenneth S. Korach.

PMID- 7629259
TI  - Citation for the 1995 Rhone-Poulenc-Rorer Clinical Investigator Award to Maria I.
      New.

PMID- 7629260
TI  - Citation for the 1995 Sidney H. Ingbar Distinguished Service Award of the
      Endocrine Society to Jacob Robbins and Joseph Edward Rall.

PMID- 7629261
TI  - Citation of the 1995 Gerald D. Aurbach Lecture Award to Robert Joseph Lefkowitz.

PMID- 7629262
TI  - Citation for the 1995 Robert H. Williams Distinguished Leadership Award of the
      Endocrine Society to David N. Orth.

PMID- 7629263
TI  - Citation for the 1995 Ernst Oppenheimer Memorial Award of the Endocrine Society
      to Deborah L. Segaloff.

PMID- 7629264
TI  - Citation for the 1995 Richard E. Weitzman Memorial Award of the Endocrine Society
      to Mitchell Avery Lazar.

PMID- 7629265
TI  - Modularity and the brain. Introduction.

PMID- 7629266
TI  - Linguistic processes in the two cerebral hemispheres: implications for modularity
      vs interactionism.
AB  - Three experiments are reported on lexical decision to target stimuli presented to
      the right or left visual field (RVF, LVF) following a variety of priming stimuli,
      words, incomplete sentences, and scrambled sentences. Lexical decision
      performance is always superior for stimuli presented to the RVF. Primes always
      facilitate the discrimination of words from nonword target stimuli presented to
      either visual field. However, when the prime is a sentence which is completed
      syntactically and semantically by a target word (normal, congruent sentence), the
      facilitation for RVF presented targets is significantly greater than for LVF
      targets. When the prime is either: (1) a single word, (2) a nonstructured
      (scrambled) sentence, or (3) a noncongruent-related sentence, the difference in
      facilitation between RVF and LVF presented targets is much smaller. These data
      are discussed with respect to (1) the nature of priming by sentences versus
      words, (2) language processing by the two hemispheres, and (3) modularity versus
      interactionism in language processing.

PMID- 7629267
TI  - Rise and fall of modular orthodoxy.
AB  - The premise of cortical modularity is based on strong dissociations caused by
      focal lesions. These dissociations are rare, and their explanatory power and
      theoretical importance are vastly overrated. The effects of brain lesions must be
      considered in their totality, rather than in idiosyncratic selectivity. These
      effects are more consistent with a continuous, graded functional neocortical
      geometry, than with a modular neocortex. Distinction must be drawn between strong
      intrinsic modularity, and weak emergent modularity. Strong intrinsic modularity
      is more characteristic of the thalamus than of the cortex. The advent of
      neocortex may have represented an evolutionary escape from strong modularity as
      the dominant principle of neural organization, and a shift toward a more
      interactive principle of neural organization dominated by emergent properties.
      The latter may take the form of weak modularity, reflective of cognitive skill
      routinization. The extent of weak, emergent modularization may be asymmetric,
      more pronounced in the left hemisphere, while the right hemisphere is essentially
      amodular.

PMID- 7629268
TI  - Domain-specific forms of neglect.
AB  - In this paper, it is assumed that domain specificity is one of the crucial
      criteria of modularity. It is also assumed that hemispatial neglect is basically
      a spatial attention deficit. Then, the literature that has shown, on the basis of
      either single or double dissociations, that neglect can be confined to very
      specific representational domains is reviewed. In particular, two recent studies
      are summarized that reported dissociations between perceptual and motor neglect
      and between visual and tactile neglect. It is suggested that disorders of spatial
      attention can affect just one spatial representational domain. This satisfies the
      domain specificity criterion of modularity and suggests that spatial attention
      mechanisms may be modular.

PMID- 7629269
TI  - Spatial attention in the mental architecture: evidence from neuropsychology.
AB  - Using neuropsychological evidence, this paper examines whether spatial attention
      functions as a domain-specific module or as a more general-purpose central
      processor. Data are presented from two spatial attention cuing tasks completed by
      subjects, with an acquired attentional deficit, and control subjects. In both
      tasks, an arrow indicated with high probability the side of response (response
      task) or the side of space on which the stimulus would appear (visuospatial
      task). In the response task, the stimuli appeared foveally and the response
      component was lateralized, and in the visuospatial task, the stimuli were
      lateralized and the response component remained constant in the midline. Only the
      neglect subjects showed a disproportionate increase in reaction time on both the
      response and visuospatial tasks when the arrow cued the subject to the
      ipsilateral side and the stimulus or response was on the side of space
      contralateral to the lesion. The substantial association across the two tasks
      suggests that a common underlying internal spatial representation subserves
      perception and action. While this finding is consistent with Fodor's view of a
      cross-domain processor, it does not meet all of his criteria of a central
      processor. We conclude, therefore, that the posterior attentional mechanism is
      strictly neither a module nor a central processor. Rather, these results suggest
      that a common attentional mechanism may subserve behavior in domains that are
      tightly coupled.

PMID- 7629270
TI  - Ventriloquist effect reinstates responsiveness to auditory stimuli in the
      'ignored' space in patients with hemispatial neglect.
AB  - We examined 6 patients with robust visual neglect following right hemisphere
      damage. All of them had signs of auditory neglect as documented by the inferior
      identification of syllables delivered through a loudspeaker on the left side.
      When the same stimuli on the left were administered in the presence of a
      fictitious source of sound (a dummy loudspeaker) visible in the homolesional
      space, a significant increase in the identification score of sounds was obtained
      (the "ventriloquist" effect). The result is in keeping with a notion of a strong
      coupling between auditory and visual systems. The effect is attributed to the
      activation by the fictitious source of sound of the audio-visual map in the left
      hemisphere. We draw attention to the possibility that loss of awareness of
      auditory input may arise due to the disconnection of the visual input from the
      audio-visual template.

PMID- 7629271
TI  - On the modularity of face recognition: the riddle of domain specificity.
AB  - The present paper focuses on the modular attributes of face recognition, defined
      in terms of domain specificity. Domain specificity is examined by looking into
      the innate nature of face recognition, the special effects related to the
      recognition of inverted faces, the specificity of electrophysiological
      responsivity to facial stimuli, and the specific impairment in face recognition
      associated with localized brain damage. Converging evidence from these sources
      seems to consistently show that face recognition is not qualitatively unique, as
      it proceeds in a manner similar to the recognition of other visuospatial objects.
      However, it seems to be special in that it may involve specific mechanisms
      dedicated to face recognition. Among infants, differential responsivity to faces
      and to other objects in terms of age of onset, attraction and course of
      development, seems to indicate the operation of a special process. Unusual
      inversion effects in face recognition might be due to the special expertise that
      humans develop for recognizing upright faces. Face-selective single unit
      responses in the monkey's brain implies the existence in the visual system of
      cells which are exclusively dedicated to the processing of facial stimuli.
      Finally, in prosopagnosia localized brain damage is linked to a specific
      inability to recognize familiar faces. Taken together, the data seem to show that
      some elements in the process of face recognition are domain specific, and in that
      sense, modular.

PMID- 7629272
TI  - Recovered consciousness: a hypothesis concerning modularity and episodic memory.
AB  - Why should conscious recollection be associated with recovery of some memories
      and not others? A hypothesis is proposed and defended that the medial temporal
      lobe/hippocampal complex (MTL/H) and related limbic structures comprise a memory
      module that receives as its input only information that is consciously
      apprehended. The module then binds or conjoins into memory traces those neural
      elements that mediated the conscious experience so that effectively
      "consciousness" is as intergral a part of the memory traces as it was during the
      experience of the event. When memory traces are retrieved, what is recovered are
      the phenomenological records (Conway, 1992) of experienced events which are
      integrated content-consciousness packets. Evidence is presented which suggests
      that the MTL/H module satisfies Fodorian criteria of modularity. The MTL/H module
      is compared to perceptual modules in nonfrontal neocortex that mediate
      performance on tests of memory without awareness and to prefrontal neocortex that
      acts as a central working-with-memory system that operates on the input to MTL/H
      and the shallow output from it.

PMID- 7629273
TI  - Double dissociation without modularity: evidence from connectionist
      neuropsychology.
AB  - Many theorists assume that the cognitive system is composed of a collection of
      encapsulated processing components or modules, each dedicated to performing a
      particular cognitive function. On this view, selective impairments of cognitive
      tasks following brain damage, as evidenced by double dissociations, are naturally
      interpreted in terms of the loss of particular processing components. By
      contrast, the current investigation examines in detail a double dissociation
      between concrete and abstract work reading after damage to a connectionist
      network that pronounces words via meaning and yet has no separable components
      (Plaut & Shallice, 1993). The functional specialization in the network that gives
      rise to the double dissociation is not transparently related to the network's
      structure, as modular theories assume. Furthermore, a consideration of the
      distribution of effects across quantitatively equivalent individual lesions in
      the network raises specific concerns about the interpretation of single-case
      studies. The findings underscore the necessity of relating neuropsychological
      data to cognitive theories in the context of specific computational assumptions
      about how the cognitive system operates normally and after damage.

PMID- 7629274
TI  - A reliable method to estimate the association constant for a monoclonal antibody
      and a protein antigen by enzyme linked immunosorbent assay, ELISA.
AB  - The association constant Ka for mouse monoclonal antibody raised against human
      angiotensinogen was calculated using a mathematical model, SAM I. K1 represents
      the equilibrium constant for the binding of antibody to the solid phase with
      antigen previously absorbed. K2 represents the interaction between antibody and
      antigen in solution (Ag + Ab = AgAb). K3 represents binding to the antigen
      absorbed on the solid phase by an antigen-antibody complex. K4 represents the
      second binding of the antigen to the antigen-antibody complex (AgAb + AgAb =
      (Ag)2Ab). The model unveils cooperativity for the first (K1 and K2) and second
      (K3 and K4) binding of antigen to antibody. The model gives the association
      constant in a high affinity interaction between antigen and antibody.

PMID- 7629275
TI  - Use of progesterone-3(O-carboxymethyl oxime)-horseradish peroxidase in a
      sensitive microtitre-plate EIA and its application to a visual membrane EIA of
      progesterone.
AB  - A simple method of visual membrane enzyme-immunoassay (EIA) for the detection of
      progesterone is described. When two types of progesterone-horseradish peroxidase
      (HRP) tracers were challenged for binding, in the presence of progesterone, to
      the monoclonal anti-progesterone antibody, 15A, coated on the microtitre plate,
      the HRP conjugated at the C-3 position (A-ring) of progesterone competed more
      effectively with progesterone to the binding site of the monoclonal antibody
      (mAb) than HRP conjugated at the C-11 position of the C-ring. By using this
      combination of mAb, 15A, and progesterone-3(O-carboxymethyloxime)-HRP (P-3CMO
      HRP), we developed a visual membrane EIA system in which free progesterone in the
      sample could be quantified by the degree of color development. In this system,
      free progesterone competed with P-3CMO-HRP for binding sites of mAb immobilized
      on the nitrocellulose membrane. The stable grey color was formed on the surface
      of membrane for progesterone-negative and no color for progesterone-positive
      sample using 3,3'-diaminobenzidine (DAB) with Co2+ as an insoluble substrate
      solution. To examine whether tetramethylbenzidine (TMB) can substitute for DAB in
      membrane EIA, an experiment was conducted where TMB was used as an insoluble
      substrate.

PMID- 7629276
TI  - Evaluation of protein-A linked monoclonal antibody latex agglutination test for
      diagnosis of nuclear polyhedrosis virus (BmNPV) of silkworm Bombyx mori L.
AB  - The symptomology of BmNPV infection in Bombyx mori L depends on the stages of
      infection. Discernible symptoms develop at later stages of infection, which leads
      to improper diagnosis and poor crop yield with sericulturists. In the present
      study development of direct and protein-A linked monoclonal antibody latex
      (PALMAL) agglutination test for the detection of BmNPV infection in silkworm is
      described. Latex beads were precoated with protein-A and then sensitised with
      monoclonal antibody MA-231 (125 micrograms/ml). PALMAL test could detect 1 x
      10(5) nuclear polyhedra/test and is ten times more sensitive than the direct
      agglutination test employing purified polyclonal antibodies. No agglutination was
      observed in presence of B. thuringiensis, S. marcescens, N. bombycis, group-A
      streptococci, Staphylococcus aureus, E. coli and normal haemolymph protein
      indicating the specificity of the test. Fifty haemolymph samples collected from
      the field were evaluated by PALMAL test. Twenty one samples having infection
      other than BmNPV, failed to show positive agglutination. Twenty five samples
      having > or = 5 x 10(6) BmNPV/ml showed positive agglutination. However, 4
      samples having < 5 x 10(6) BmNPV/ml failed to show positive agglutination thereby
      indicating the limit of sensitivity of the assay.

PMID- 7629277
TI  - Stability of freeze dried horseradish peroxidase conjugated monoclonal antibodies
      used in diagnostic serology.
AB  - Two murine monoclonal antibodies, an IgG1 isotype specific for the heavy chain of
      bovine IgG1, the second an IgG3 isotype and specific for an epitope of the O
      polysaccharide of Brucella abortus were conjugated with horseradish peroxidase.
      The conjugated antibodies were freeze dried in the presence of a number of
      additives to preserve activity and tested for stability over an 18 month period.
      Addition of 0.3M trehalose or 0.8% lactalbumin and 3.2% sucrose resulted in the
      lowest loss of activity if the conjugated antibodies were freeze dried in glass
      vials. Freeze drying in polypropylene vials resulted in a more rapid rate of
      deterioration with some additives or an accelerated rate of decline after an
      initial plateau of lesser loss of activity. The use of polypropylene vials and
      lactalbumin and sucrose were included in this study because of their low cost
      compared to glass vials and trehalose. While each antibody behaved differently,
      addition of trehalose or lactalbumin and sucrose to the conjugated antibodies
      aided in the preservation of enzyme activity. Both additives provide a suitable
      method for long term storage of freeze dried or freeze dried and reconstituted
      monoclonal antibody-enzyme conjugates.

PMID- 7629278
TI  - Non-instrumental immunoassay based on coloured polyacrolein latex: application to
      group-specific polysaccharide of Streptococcus pyogenes.
AB  - Non-instrumental immunoassay methods based on immunofiltration and microtiter
      particle agglutination (MPA) techniques have been developed using coloured
      polyacrolein latex. These methods have been applied to the quantification of the
      group-specific polysaccharide, A-PS, of S.pyogenes (group A Streptococcus) and
      compared to the standard ELISA tests. The assay with the ability to detect the
      lowest concentration of antigen was MPA; as little as 0.05 ng A-PS/ml or 10(4)
      cells/ml could be detected in 1.5 h. In comparison to ELISA test the sensitivity
      of MPA was 10 times higher and the procedure of the assay was much more simple.
      The sensitivity of the immunofiltration assay using both enzyme and latex markers
      was shown to be the same (50 ng A-PS/ml) and the duration of the assay 3-5 min.
      No cross-reactions of latex conjugates with non A Streptococcus cell lysates have
      been observed. The developed methods are easy to perform and require neither
      sophisticated equipment nor specially trained personal.

PMID- 7629279
TI  - Production of a new monoclonal antibody specific to human des-gamma
      carboxyprothrombin in the presence of calcium ions. Application to the
      development of a sensitive ELISA-test.
AB  - In order to explore pathologies possibly associated with vitamin K deficiency,
      several monoclonal antibodies (mAbs) were produced against human Desgamma-Carboxy
      Prothrombin (DCP). One of these mAbs, designated C4B6, detected DCP forms in the
      presence of Calcium ions, confirmed by comparison with the patterns of two
      electrophoretic techniques: Affino-Immuno-Electrophoresis (CAIE) and
      Polyacrylamide Gel Electrophoresis followed by Electro-blotting (PAGE-Blot). An
      Enzyme-Linked-Imunosorbent Assay (ELISA) using mAb C4B6 has been developed,
      optimized and standardized. It has proven to be specific for DCP forms and has a
      minimum sensitivity of 0.156 A.U/ml.

PMID- 7629280
TI  - The biology of low grade MALT lymphoma.

PMID- 7629281
TI  - Public perception of histopathology.

PMID- 7629282
TI  - Have declining clinical necropsy rates reduced the contribution of necropsy to
      medical research?
AB  - AIMS: To examine trends in necropsy based research output for a period of 27
      years during which there has been a progressive decline in clinical necropsy
      rates. METHODS: The numbers of necropsy based research papers published between
      1966 and 1993 were determined using the CD-Plus Medline computed literature
      database. RESULTS: The number of necropsy based research papers containing
      necropsy or a synonym in the title increased by 220% between 1966 and 1993. When
      papers including necropsy or a synonym in the abstract, but not in the title,
      were included, the proportion of all indexed papers increased from 0.35% in 1975,
      when abstracts were first included, to 0.53% in 1993. Analysis of the subject
      material indicated that necropsy based research has constantly reflected trends
      and advances in clinical medicine. Neuroscience related research represented the
      largest subject category which may reflect the difficulties in obtaining human
      tissue from sources other than necropsy. CONCLUSIONS: The modern necropsy
      continues to provide valuable information for all clinical and laboratory based
      disciplines. The decline in clinical necropsy rates would not yet appear to have
      undermined the contribution of the necropsy to research.

PMID- 7629283
TI  - Multifactorial audit of invasive cervical cancer: key lessons for the National
      Screening Programme.
AB  - AIMS: To audit factors associated with the development of invasive cervical
      cancer. METHODS: Twenty cases of invasive cervical cancer in one health district
      for 1991-93 were audited by multifactorial analysis. RESULTS: The average age was
      53 years with 20% (4/20) aged over 65 years. Of the patients, 45% (9/20) were
      identified by a cervical smear, with 40% (8/20) from the National Screening
      Programme (NSP) and 5% (1/20) opportunistically; 30% (6/20) had not received a
      smear, 10% (2/20) being aged under 65 and 20% 65 or over. Those with no smear had
      all been hospital patients during the previous five years. No response to a smear
      invitation occurred in 5%. In 20%, there had been a true negative smear two to
      five years previously. Inappropriate laboratory diagnosis or inappropriate
      clinical management occurred in 30% and 15% (3/20), respectively. In 20%, two or
      more factors were present in the same patient. CONCLUSIONS: Why cervical cancer
      occurs after a true negative smear requires research and women aged over 65 with
      no smear must be targeted. Failsafe systems should incorporate inadequate smears
      and smear adequacy should be given priority in quality assurance (QA) and
      training. False negative reports must be minimised but accepted as an inherent
      part of the NSP and not an automatic indicator of poor laboratory performance.
      Comprehensive national QA standards are required, to which providers must
      conform. Postcoital bleeding is an absolute indication for a smear and, when
      appropriate, opportunistic smears offered at all hospital attendance. Cervical
      cancer audit must be guaranteed access to all clinical and laboratory information
      and be seen as a means to improve the effectiveness and quality of the NSP.

PMID- 7629284
TI  - Composition of cervical smears in patients with and without a cervical ectropion.
AB  - AIMS: To test the hypothesis that absence of squamous cells in cervical smears
      obtained by an endocervical sampling technique is more prominent in patients with
      a cervical ectropion. METHODS: Prospective study exploring the relation between
      the composition of cervical smears obtained using an endocervical cotton swab in
      patients with (n = 188) and without (n = 341) a cervical ectropion. Subjects were
      529 consecutive patients from whom a cervical smear was prepared at a university
      gynaecological clinic. RESULTS: In 7% of the endocervical samples no squamous
      cells were found. There was no correlation, however, between the presence or the
      size of an ectropion and the absence of squamous cells in those samples.
      CONCLUSIONS: It was confirmed that endocervical sampling alone is insufficient to
      obtain good quality cervical smears. The presence of an ectropion proved to be an
      unreliable predictor of the absence of squamous cells.

PMID- 7629285
TI  - Antibodies to human papillomavirus type 16 E7 related to clinicopathological data
      in patients with cervical carcinoma.
AB  - AIMS: To investigate the correlation between antibodies to the transforming
      protein E7 of human papillomavirus (HPV) type 16 and clinicopathological indices
      in women with cervical squamous carcinoma. METHODS: A synthetic peptide of the
      HPV type 16 E7 protein (amino acids 6 to 35) was used to screen sera from 29
      children, 130 women with cervical intraepithelial neoplasia, 443 women with
      cervical cancer, and 222 controls, for antibodies against this viral antigen.
      Bivariate and multivariate analyses were used to investigate the correlation
      between the serological status in the pretreatment sera and clinicopathological
      indices (size of the lesions, histological grade, stomal infiltration, vascular
      invasion, and nodal spread). Survival analysis was done using the Cox regression
      model for all FIGO stages and stages IB and ILA. RESULTS: Cervical carcinoma
      patients had a significantly higher prevalence of antibodies to synthetic peptide
      E7/6-35 than women with cervical intraepithelial neoplasia (17.7% v 7%, p <
      0.005) or controls (17.7% v 11%, p < 0.05). Bivariate analysis of the data on the
      presence of anti-E7/6-35 antibodies in the pretreatment sera from these patients
      and clinicopathological indices showed a significant correlation between the
      presence of anti-E7/6-35 antibodies and the size of the lesion (p = 0.0009),
      histological grade (p = 0.0031), and lymph node metastasis (p = 0.01). 0.011). In
      addition, the Cox regression model, analysing four risk factors which can be
      determined before treatment, showed a significant correlation between the
      presence of anti-E7/6-35 antibodies and a worse prognosis (p = 0.003). Survival
      analysis revealed that both for all FIGO stages (p = 0.0005) and for stages IB
      and IIA alone (p = 0.0021), anti-E7/6-35 positive patients before treatment had a
      significantly shorter life expectancy. CONCLUSIONS: The presence of antibodies
      against E7/6-35 in pretreatment sera from patients with cervical carcinoma
      correlates with the size of the lesions, lymph node involvement, and a worse
      prognosis.

PMID- 7629286
TI  - Comparative analysis of human papillomavirus detection by PCR and non-isotopic in
      situ hybridisation.
AB  - AIMS--To assess the relative diagnostic performance of the polymerase chain
      reaction (PCR) and non-isotopic in situ hybridisation (NISH) and to correlate
      these data with cytopathological assessment. METHODS--Paired analysis of human
      papillomavirus (HPV) detection was performed by PCR and NISH on exfoliated
      cervical cells from 122 women attending a routine gynaecological examination. PCR
      amplification followed by generic and HPV type specific hybridisation was
      compared with NISH on a parallel cervical smear. RESULTS--Overall, 32 cases were
      positive by NISH and 61 positive by PCR. Of the 105 cases in which both PCR and
      NISH were interpretable, 76 (26%) were normal smears, 20 of which were HPV
      positive by NISH and 37 (49%) by PCR. Of 17 borderline smears, two were NISH
      positive and 12 PCR positive. Eight of nine smears containing koilocytes were
      positive by NISH and seven by PCR. Of three dyskaryotic smears, none were NISH
      and two were PCR positive. The concordance of NISH and PCR in these samples was
      57%. To assess sampling error, NISH and PCR were performed on an additional 50
      cases using aliquots from the same sample. This increased the concordance between
      assays to 74%. Filter hybridisation of PCR products with the cocktail of probes
      used in NISH (under low and high stringency conditions) demonstrated that several
      cases of NISH positivity could be accounted for by cross-hybridisation to HPV
      types identified by PCR but not present in the NISH probe cocktail. CONCLUSIONS-
      Sampling error and potential cross-hybridisation of probe and target should be
      considered in interpretation of these techniques. PCR is more sensitive because
      it provides for the amplification of target DNA sequences. In addition, the PCR
      assay utilised in this study detects a wider range of HPV types than are
      contained in the cocktails used for NISH. However, PCR assays detect viral DNA
      present both within cells and in cervical fluid whereas NISH permits
      morphological localisation.

PMID- 7629287
TI  - Observer reliability in assessing placental maturity by histology.
AB  - AIMS: To evaluate the ability of five experienced perinatal pathologists to
      assess placental maturity reliably by histology. METHODS: Twenty four
      haematoxylin and eosin slides, six each from placentas of 27, 31, 35, and 39
      weeks' gestation, were circulated to five pathologists on three separate
      occasions. The slides were labelled with the correct or incorrect gestational
      ages. RESULTS: The mean absolute error over all 360 readings was 2.72 weeks. Only
      54% of the slides were assessed within two weeks of the correct gestation.
      Pathologist tended to overestimate younger gestations and underestimate older
      gestations. Two, and possibly three, pathologist were influenced by the
      gestational age state on the label. One pathologist, who did not appear to be
      influenced by the label, was more accurate in diagnosing gestation of the
      placentas than other colleagues. CONCLUSIONS: Experienced pathologists can have
      difficulty in assessing the villous maturity of placentas by histology. They can
      also be influenced by clinical information provided, such as gestational age.
      Other observer reliability studies must address the issue of the influence of
      labelled information on observer variation. A difference in maturation would have
      to be of a six week magnitude to have a chance of being detected by current
      methods. This may limit the value of the histological diagnosis of placental
      dysmaturity as a surrogate marker for uteroplacental ischaemia.

PMID- 7629288
TI  - Loss of heterozygosity on chromosome 11 q in breast cancer.
AB  - AIMS: Chromosome 11q23 seems to be a site of frequent mutation in cancer. It also
      contains loci such as ataxia telangiectasia with possible importance in the
      pathogenesis of breast tumours. The short arm of chromosome 11 has been studied
      extensively in breast cancer, but the long arm, in particular the distal part,
      has been studied less frequently. Cytogenetic analysis has shown possible
      involvement of chromosome 11q in breast tumours. Chromosome transfer experiments
      have also implicated chromosome 11q in breast cancer. A high frequency of
      mutations might therefore be expected to occur on chromosome 11q in breast
      cancers. METHODS: Using restriction fragment analysis, the primary tumours of 41
      patients with breast cancer were screened for mutations at five loci on
      chromosome 11q (D11Z1, INT2, (FGF3), DRD2, NCAM, and D11S29). RESULTS: Allelic
      loss occurred at a high frequency (59%) at D11S29. At NCAM, novel alleles were
      frequently seen on autoradiographs. Relatively low frequencies of mutation were
      detected at the other loci. Allelic loss at D11S29 was associated with the
      presence of lymph node metastases, but this may be a chance association.
      CONCLUSIONS: The frequency of allelic loss at the DS11S29 locus is high. The
      significance of novel alleles at NCAM and their relation to allelic loss at
      D11S29 are unclear. The results presented here do not permit fine mapping of a
      region of allelic loss, but suggest that the region of greatest loss lies distal
      to DRD2. The results provide further evidence for the importance of gene(s) near
      11q23 in the pathogenesis of breast cancer, and of tumours in general.

PMID- 7629289
TI  - Immunohistochemical quantitation of oestrogen receptors and proliferative
      activity in oestrogen receptor positive breast cancer.
AB  - AIM: To evaluate the effect of the duration of formalin fixation and of tumour
      heterogeneity on quantitative estimates of oestrogen receptor content (oestrogen
      receptor index) and proliferative activity (MIB-1 index) in breast cancer.
      METHODS: Two monoclonal antibodies, MIB-1 and oestrogen receptor, were applied to
      formalin fixed, paraffin wax embedded tissue from 25 prospectively collected
      oestrogen receptor positive breast carcinomas, using a microwave antigen
      retrieval method. Tumour tissue was allocated systematically to different periods
      of fixation to ensure minimal intraspecimen variation. The percentages of MIB-1
      positive and oestrogen receptor positive nuclei were estimated in fields of
      vision sampled systematically from the entire specimen and from the whole tumour
      area of one "representative" cross-section. RESULTS: No correlation was found
      between the oestrogen receptor and MIB-1 indices and the duration of formalin
      fixation. The estimated MIB-1 and oestrogen receptor indices in tissue sampled
      systematically from the entire tumour were closely correlated with estimates
      obtained in a "representative" section. The intra- and interobserver correlation
      of the MIB-1 index was good, although a slight systematical error at the second
      assessment of the intraobserver study was noted. CONCLUSION: Quantitative
      estimates of oestrogen receptor content and proliferative activity are not
      significantly influenced by the period of fixation in formalin, varying from less
      than four hours to more than 48 hours. The MIB-1 and the oestrogen receptor
      indices obtained in a "representative" section do not deviate significantly from
      average indices determined in tissue samples from the entire tumour. Finally, the
      estimation of MIB-1 index is reproducible, justifying its routine use.

PMID- 7629290
TI  - Immunocytological analysis of the Tn associated antigen 83D4 in serous effusions
      from patients with cancer: comparison with Tn soluble glycoprotein.
AB  - AIMS: To determine whether the monoclonal antibody (MoAb) 83D4, previously shown
      to be highly specific for carcinoma cells, can be used as an immunocytological
      marker to discriminate between benign and malignant cells in serous effusions;
      and to test for a correlation between expression of the antigen reacting with
      MoAb 83D4 on effusion cells and the amount of soluble 83D4 antigen in effusion
      fluids. METHODS: Thirty three pleural and 23 peritoneal effusions from 56 cancer
      patients with metastatic disease were tested for the presence of Tn associated
      83D4 antigen by immunocytochemical staining, and for the presence of soluble
      antigen in supernatants. The patients had undergone various chemotherapy and
      radiation therapy protocols. RESULTS: As a result of the various types of
      treatment, the cytological characteristics of the cells were often modified and
      the antigenic epitopes may have been altered. Positive staining for 83D4 MoAb was
      obtained in 36 (97%) of the 37 malignant effusions, eight (73%) of 11 suspect
      effusions, and three (38%) of the eight apparently benign effusions (free of
      malignant cells). In these latter cases, cytological reassessment showed a few
      suspect cells in two cases. 83D4 soluble antigen was detected in 30 of 37
      malignant effusions (81%), five of 11 suspected infusions (46%), and five of
      eight apparently benign effusions (63%). CONCLUSIONS: Immunocytochemical staining
      with anti-83D4 antibody is useful for differentiating reactive or atypical
      mesothelial cells from epithelial cells, especially in breast cancer effusions.

PMID- 7629291
TI  - Cytodiagnosis and the necropsy.
AB  - AIMS: To assess the efficacy of cytodiagnosis in necropsy practice. METHODS:
      Fifty three focal lesions from 46 necropsies were assessed by direct smears taken
      from the lesions. The smears were air-dried and stained by a modified Giemsa
      technique, with two cases having supplementary histochemistry. All of the slides
      were assessed independently before review of the necropsy histology. RESULTS: Of
      the 35 malignant neoplasms, 34 were correctly identified as malignant and 14 of
      these were characterised precisely. Three of the four benign neoplasms were
      recognised as neoplastic. One was characterised precisely. Three of the four
      infected cases revealed the relevant microorganisms. Seven of the other 10 focal
      non-neoplastic lesions were correctly diagnosed as non-neoplastic. Only two cases
      proved unsatisfactory for cytodiagnosis. CONCLUSIONS: Direct smear cytodiagnosis
      is quick, cheap and technically simple. Tissue autolysis may account for some
      difficulty in assessing particular tissues, but this should diminish with
      experience. Necropsy cytodiagnosis is applicable to all necropsies in all
      centres.

PMID- 7629292
TI  - Oncogene proteins and proliferation antigens in thymomas: increased expression of
      epidermal growth factor receptor and Ki67 antigen.
AB  - AIMS: To examine thymomas for proteins encoded by oncogenes and to determine
      whether their presence correlates with tumour growth and associated myasthenia
      gravis. METHODS: Sections of 24 thymomas were incubated with anti-EGF receptor
      (EGF-R), anti-Ki67 antigen, anti-p53, and anti-bcl-2 antibodies, and then stained
      using the alkaline phosphatase/anti-alkaline phosphatase (APAAP) technique. Cell
      suspensions and epithelial cell cultures from some of the tumours were also
      studied. RESULTS: Whereas EGF-R expression was not detected in any of the
      controls (but only in a 20 week old fetus), it was detected in neoplastic
      epithelial cells of all thymomas, and was most strongly expressed in metastases
      and in samples from donors with severe myasthenia gravis. Ki67 labelling was also
      increased, especially in the larger thymomas. Epithelial expression of both of
      these markers was confirmed in fresh cell suspensions and monolayer cultures from
      the five available cases. In contrast, p53 and bcl-2 were not detected in the
      neoplastic cells, but bcl-2 was present in the intermingling thymocytes.
      CONCLUSIONS: Neoplastic thymoma cells express EGF-R and Ki67, but there is no
      concomitant increase in the expression of p53 and bcl-2 proteins. Increased EGF-R
      expression may result in increased proliferation of neoplastic cells and also in
      myasthenia gravis. Measurement of EGF-R concentrations may be of prognostic
      value. The bcl-2 staining pattern in T lymphocytes illustrates the broad spectrum
      of maturational stages in thymoma lymphocytes.

PMID- 7629293
TI  - Light scatter characteristics of blast cells in acute myeloid leukaemia:
      association with morphology and immunophenotype.
AB  - AIMS: To analyse the forward scatter/side scatter (FSC/SSC) distribution of acute
      myeloblastic leukaemia (AML) blast cells in order to assess whether it correlates
      with their morphology, immunophenotype, and clinical and biological disease
      characteristics. METHODS: FSC/SSC patterns were established upon taking into
      account the localisation of the residual T lymphocytes in the FSC/SSC dot plot as
      an internal biological standard. One hundred and seventy one newly diagnosed AML
      patients were analysed and five different FSC/SSC patterns were established.
      These five patterns could be grouped into two major categories taking into
      account the FSC/SSC distribution of normal cells in a bone marrow aspirate:
      immature patterns (1 and 2) and mature patterns (3, 4, and 5). These FSC/SSC
      patterns were correlated with different clinical and biological characteristics
      of AML patients. RESULTS: No significant associations were detected in relation
      to the clinical and haematological disease characteristics and the prognosis of
      these patients. By contrast there was a significant correlation between the
      FSC/SSC pattern of the AML blast cells and the FAB classification. An increased
      reactivity for the antigens associated with myeloid differentiation such as CD13,
      CD33, CD11b, CD15, CD14, CD4, CD56, and/or CD16 was detected among cases showing
      a mature FSC/SSC pattern (3, 4, and 5), both in the whole series and even within
      each of the FAB AML subtypes. By contrast, the reactivity for the CD34 precursor
      cell associated antigen was higher among those cases displaying an immature
      FSC/SSC pattern, this being observed even within each FAB subgroup. CONCLUSIONS:
      The FSC/SSC pattern distribution of AML blast cells not only provides an
      additional objective and reproductible system for the classification of these
      leukaemias but it may also represent a connection between the FAB morphological
      groups and the immunophenotypic classification of AML patients.

PMID- 7629294
TI  - Thyroid antoantibodies and the response to thyrotropin releasing hormone in
      patients with subclinical hypothyroidism.
AB  - AIM: To evaluate the clinical usefulness of the thyrotropin releasing hormone
      (TRH) test and estimation of thyroid autoantibody concentrations in patients with
      borderline raised thyroid stimulating hormone (TSH). METHODS: The records of 34
      consecutive patients with persistent borderline increased TSH (4.4-9.9 mU/l)
      referred to the Medical Investigation Unit were reviewed. The response of
      patients with thyroid autoantibodies to the TRH test was compared with that of
      patients with a negative antibody screen. RESULTS: Eleven (44%) of 25 patients
      with positive anti-thyroid microsomal and/or thyroglobulin antibody tests and
      three (33%) of nine patients with a negative antibody screen had hypothyroid
      responses to TRH. Neither age nor sex affected the response to TRH. Basal TSH
      alone was poorly correlated with these indices. Twelve (35%) patients who had
      elevated basal TSH had a normal response to the TRH test. CONCLUSION: Patients
      with positive or negative thyroid autoantibodies and an exaggerated response to
      the TRH test should be regarded as hypothyroid and treated with thyroxine.
      Patients with positive thyroid autoantibodies and normal TSH response may
      subsequently develop hypothyroidism and should be given long term follow up.

PMID- 7629295
TI  - Volatile organic compounds in the breath of patients with schizophrenia.
AB  - AIMS: To analyse the breath of patients with schizophrenia for the presence of
      abnormal volatile organic compounds. METHODS: A case comparison study was
      performed in two community hospitals in Staten Island, New York. Twenty five
      patients with schizophrenia, 26 patients with other psychiatric disorders, and 38
      normal controls were studied. Alveolar breath samples were collected from all
      participants, and volatile organic compounds in the breath were assayed by gas
      chromatography with mass spectroscopy. Differences in the distribution of
      volatile organic compounds between the three groups were compared by computerised
      pattern recognition analysis. RESULTS: Forty eight different volatile organic
      compounds were observed in the breath samples. Three separate pattern recognition
      methods indicated an increased differentiation capability between the patients
      with schizophrenia and the other subjects. Pattern recognition category
      classification models using 11 of these volatile organic compounds identified the
      patients with schizophrenia with a sensitivity of 80.0% and a specificity of
      61.9%. Volatile organic compounds in breath were not significantly affected by
      drug therapy, age, sex, smoking, diet, or race. CONCLUSIONS: Microanalysis of
      volatile organic compounds in breath combined with pattern recognition analysis
      of data may provide a new approach to the diagnosis and understanding of
      schizophrenia. The physiological basis of these findings is still speculative.

PMID- 7629296
TI  - Membrane staining for hepatitis B surface antigen on hepatocytes: a sensitive and
      specific marker of active viral replication in hepatitis B.
AB  - AIMS--To test the hypothesis that membranous staining of hepatitis B surface
      antigen (HBsAg) on the hepatocyte is a marker of active viral replication in
      chronic hepatitis B virus (HBV) infection. METHODS--Intrahepatic expression of
      HBsAg and hepatitis B core antigen (HBcAg) was studied by indirect
      immunofluorescence on frozen sections of liver specimens from 75 patients with
      chronic hepatitis B, and the results were correlated with serum levels of HBV-DNA
      assayed by spot hybridisation. RESULTS--Hepatocyte HBcAg was detected in all of
      20 patients with serum levels of HBV-DNA > 1000 pg/ml, 18 (75%) of 24 patients
      with levels of HBV-DNA < or = 1000 pg/ml, and two (6.5%) of 31 patients without
      detectable serum HBV-DNA. The concordance between hepatocyte HBcAg and serum HBV
      DNA was 89.3% (67/75). There were six patients (8%) who had detectable serum HBV
      DNA but without hepatocyte HBcAg, and two patients (2.7%) who had detectable
      hepatocyte HBcAg but without serum HBV-DNA. Membranous staining of HBsAg
      associated with variable degrees of cytoplasmic HBsAg was found in all but one of
      44 patients with serum HBV-DNA, irrespective of the levels, but in none of the 31
      patients without serum HBV-DNA. Of the latter, HBsAg was distributed solely in
      the cytoplasm. In addition, there is an inverse correlation between serum levels
      of HBV-DNA and the degrees of cytoplasmic staining of HBsAg. The concordance
      between membranous staining fo HBsAg and serum HBV-DNA was 98.7% (74/75),
      significantly higher than that between hepatocyte HBcAG and serum HBV-DNA.
      CONCLUSIONS--Membranous staining of HBsAg on the hepatocyte correlated
      excellently with serum HBV-DNA and thus can be recognised as a sensitive and
      specific marker of active hepatitis B virus replication.

PMID- 7629297
TI  - Clinical evaluation and reproducibility of the Pastorex Aspergillus antigen latex
      agglutination test for diagnosing invasive aspergillosis.
AB  - AIMS: The performance of the Pastorex Aspergillus antigen latex agglutination
      test for the detection of galactomannan in sera of patients at risk for invasive
      aspergillosis was evaluated, and the impact of storage on the reproducibility of
      the antigen titre was tested. METHODS: During a one year period, 392 serum
      samples were obtained from 46 patients at risk for invasive aspergillosis and
      tested for the presence of galactomannan using an Aspergillus latex agglutination
      test (Pastorex). Twenty three positive serum samples which had been stored at -20
      degrees C for 2-16 months were retrospectively retested. Furthermore, two
      positive serum samples were stored at -20 degrees C and -70 degrees C and
      prospectively tested at three month intervals for a period of 15 months. RESULTS:
      The Pastorex Aspergillus test was positive in eight patients with
      microbiological, radiological, or histological evidence for invasive
      aspergillosis, but was negative in the initial serum sample from five of these
      patients. In two patients with histological evidence for invasive aspergillosis
      no positive reaction was found in six samples. Six of 13 (45%) serum samples
      which had been stored at -20 degrees C for longer than six months had lost
      reactivity, while one of 10 (10%) samples had lost reactivity when stored up to
      six months. Two serum samples which had been stored at -20 degrees C and -70
      degrees C and prospectively retested at three month intervals for 15 months,
      maintained stable antigen titres. CONCLUSIONS: The Pastorex Aspergillus test is
      too insensitive to diagnose invasive aspergillosis in an early stage, but may
      contribute to the diagnosis when cultures remain negative and serial samples are
      obtained. To maintain a good reproducibility, serum samples should be stored at 
      70 degrees C when the period of storage exceeds six months.

PMID- 7629298
TI  - Plasma cell proliferation in monoclonal gammopathies: measurement using BU-1
      antibody in flow cytometry and microscopy: comparison with serum thymidine
      kinase.
AB  - AIMS: The labelling index as defined by the percentage of bone marrow plasma
      cells doubling their DNA in the S phase is a useful prognostic factor in multiple
      myeloma. The aim of this study was to examine the specificity and sensitivity of
      a new flow cytometric method for measuring the labelling index. METHODS: Bone
      marrow specimens from five patients with monoclonal gammopathy of undetermined
      significance and 61 patients with multiple myeloma were investigated. The
      labelling index (LI%) was determined by means of a microscopic and flow
      cytometric method using the antibromodeoxyuridine antibody BU-1. Serum thymidine
      kinase, another index of proliferation, was measured by radioimmunoassay.
      RESULTS: Good comparability (r = 0.83) and nearly equal imprecision (CV < 20%)
      were found with microscopic and flow cytometric methods of LI% measurement.
      However, 1000 or more cells had to be counted by microscopy around the cutoff
      value to avoid an unacceptable imprecision. Plasma cells with increased S phase
      (LI% > 1%) were characterised by their reduced light chain fluorescence intensity
      ratio between plasma cells and nonspecifically stained cells (7.9 v 14.8, p <
      0.002), that is, by their generally lowered cytoplasmic immunoglobulin content.
      There was a moderate correlation between thymidine kinase and labelling index (r
      = 0.56, p < 0.001). At 100% specificity, myelomas with proliferating plasma cells
      were more sensitively detected by the labelling index than by serum thymidine
      kinase (55% v 32% sensitivity). CONCLUSIONS: The labelling index represents a
      more specific and sensitive proliferation marker than serum thymidine kinase.
      Flow cytometry does not result in greater precision.

PMID- 7629300
TI  - False negative results in enzyme linked immunosorbent assays using synthetic HIV
      antigens.
AB  - The sensitivity of 12 commonly used anti-HIV-1/HIV-2 enzyme immunoassays was
      evaluated. The assays, each of which utilises at least one synthetic HIV antigen,
      were tested against a panel of 1092 specimens previously designated anti-HIV
      positive. In a total of 13 104 tests there were eight false negative results
      attributable to assay insensitivity: three were on two serum samples collected
      close to seroconverison and five on another serum specimen. These eight false
      negative results arose in seven different assays. Five other false results were
      attributable to technical error. This false negativity rate indicates that all of
      the assays performed adequately and leads to an estimate of one false negative
      result in a thousand tests in routine diagnostic practice. Because of the
      antigenic heterogeneity of HIV strains, similar evaluations would be required in
      several regions before this satisfactory level of sensitivity in anti-HIV assays
      incorporating synthetic antigens could be said to be universal.

PMID- 7629299
TI  - Effect of interleukins on the proliferation and survival of B cell chronic
      lymphocytic leukaemia cells.
AB  - AIMS: To investigate the effects of interleukin (IL) 1, 2, 4, and 5 on the
      proliferation and survival of peripheral blood B cells from patients with B
      chronic lymphocytic leukaemia (B-CLL) and compare them with the effects on normal
      peripheral blood B cells. METHODS: The proliferation and survival of pokeweed
      mitogen (PWM) activated B cells from B-CLL (n = 12) and normal peripheral blood
      (n = 5) were studied in vitro in response to IL-1, IL-2 IL-4, and IL-5. Survival
      of cells in cultures with or without added interleukins was studied by
      microscopic examination of cells and DNA agarose gel electrophoresis. RESULTS:
      Proliferation was observed in both B-CLL and normal peripheral blood cells on
      culture with IL-2 alone and also in some, but not all, B-CLL and normal
      peripheral blood cells with IL-1 and IL-4. However, there was greater variability
      in B-CLL cell responses than in normal peripheral blood cells. Il-5 did not
      affect normal peripheral blood cell proliferation but it increased proliferation
      in two B-CLL cases. Synergistic effects of these cytokines were not detected. IL
      4 inhibited normal peripheral blood and B-CLL cell proliferation after the
      addition of IL-2. Inhibition of B-CLL cell responses to IL-2 was also observed
      with IL-5 and Il-1. Survival of B-CLL cells in cultures was enhanced with IL-4
      not by an increase in proliferation but by reduced apoptosis. No such effect was
      seen in normal peripheral blood cells. IL-2 had a less noticeable antiapoptotic
      effect; IL-5 enhanced apoptosis in B-CLL cells. CONCLUSIONS: B-CLL and normal
      peripheral blood cells proliferated equally well in response to IL-2. IL-4 had a
      much lower effect on B-CLL cell proliferation, but had noticeable antiapoptotic
      activity. IL-5 enhanced cell death by apoptosis.

PMID- 7629301
TI  - Anticomplementary activity in serum samples from patients with acute parvovirus
      B19 infection.
AB  - Of 65 serum samples submitted for diagnostic purposes which proved to be anti
      complementary by complement fixation test, 49 were parvovirus B19 IgM positive.
      Forty four of the 49 serum samples were from patients with arthropathy. Acute
      parvovirus B19 infection should be suspected when a patient has symptoms of
      disease of the joints and the serum is anticomplementary.

PMID- 7629303
TI  - Isolated testicular vasculitis mimicking a testicular neoplasm.

PMID- 7629302
TI  - Expression of MHC class II antigens by placental villi: no relationship with
      villitis of unknown origin.
AB  - The aim of the study was to determine whether immunoreactivity to major histo
      compatibility complex (MHC) class II antigens studied by immunohisto-chemistry
      could be used reliably to define villitis lesions in placenta. Eighteen placental
      sections with villitis and 32 without, as determined in a careful observer
      reproducibility study, were immunolabelled with a monoclonal antibody to
      monomorphic determinants of MHC class II antigens (CR3/43), using a standard
      avidin-biotin peroxidase technique. Placentas with villitis were found to express
      MHC class II antigens. However, some showed no immunoreactivity. Occasional villi
      unaffected by villitis, including those near placental infarcts, also expressed
      MHC class II antigens. The study therefore showed that immunohistochemistry
      cannot be used to define villitis of unknown aetiology. It provides further
      evidence of the difficulties that can arise when immunohistochemistry conflicts
      with previous light microscopy findings.

PMID- 7629304
TI  - Anatomical compartments in the white matter of the rabbit flocculus.
AB  - The white matter of the rabbit flocculus is subdivided into five compartments by
      narrow sheets of densely staining acetylcholinesterase-positive fibers. The most
      lateral compartment is continuous with the C2 compartment of the paraflocculus
      and contains the posterior interposed nucleus. The other four compartments are
      numbered from lateral to medial as floccular compartments 1, 2, 3, and 4 (FC1-4).
      FC1-3 continue across the posterolateral fissure into the adjacent folium (folium
      p) of the ventral paraflocculus. FC4 is present only in the rostral flocculus. In
      the caudal flocculus FC1 and FC3 abut dorsal to FC2. Fibers of FC1-4 can be
      traced into the lateral cerebellar nucleus and the floccular peduncle. The
      presence of acetylcholinesterase in the deep stratum of the molecular layer of
      the flocculus and ventral paraflocculus distinguishes them from the dorsal
      paraflocculus. The topographical relations to the flocculus and the floccular
      peduncle with group y and the cerebellar nuclei are discussed.

PMID- 7629306
TI  - Double labeling of GABA and cytochrome oxidase in the macaque visual cortex:
      quantitative EM analysis.
AB  - In the primate striate cortex, cytochrome oxidase (CO)-rich puffs differ from CO
      poor interpuffs in their metabolic levels and physiological properties. The
      neurochemical basis for their metabolic and physiological differences is not well
      understood. The goal of the present study was to examine the relationship between
      the distribution of gamma aminobutyric acid (GABA)/non-GABA synapses and CO
      levels in postsynaptic neuronal profiles and to determine whether or not a
      difference existed between puffs and interpuffs. By combining CO histochemistry
      and postembedding GABA immunocytochemistry on the same ultrathin sections, the
      simultaneous distribution of the two markers in individual neuronal profiles was
      quantitatively analyzed. In both puffs and interpuffs, GABA-immunoreactive (GABA
      IR) neurons were the only cell type that received both non-GABA-IR (presumed
      excitatory) and GABA-IR (presumed inhibitory) axosomatic synapses, and they had
      three times as many mitochondria darkly reactive for CO than non-GABA-IR neurons,
      which received only GABA-IR axosomatic synapses. GABA-IR neurons and terminals in
      puffs had a larger mean size, about twice as many darkly reactive mitochondria,
      and a higher ratio of non-GABA-IR to GABA-IR axosomatic synapses than those in
      interpuffs (2.3:1 vs. 1.6:1; P < 0.01). There were significantly more synapses of
      both non-GABA-IR and GABA-IR types in the neuropil of puffs than of interpuffs;
      however, the ratio of non-GABA-IR to GABA-IR synapses was significantly higher in
      puffs (2.86:1) than in interpuffs (2.08:1; P < 0.01). Our results are consistent
      with the hypothesis that the level of oxidative metabolism in postsynaptic
      neurons and neuronal processes is tightly governed by the strength and proportion
      of excitatory over inhibitory synapses. Thus, the present results suggest that
      (1) GABA-IR neurons in the macaque striate cortex have a higher level of
      oxidative metabolism than non-GABA ones because their somata receive direct
      excitatory synapses and their terminals are more tonically active; (2) the higher
      proportion of presumed excitatory synapses in puffs imposes a greater energy
      demand there than in interpuffs; and (3) excitatory synaptic activity may be more
      prominent in puffs than in interpuffs because puffs receive a greater proportion
      of excitatory synapses from multiple sources including the lateral geniculate
      nucleus, which is not known to project to the interpuffs.

PMID- 7629305
TI  - Ultrastructural examination of the targets of serotonin-immunoreactive descending
      interneurons in the guinea pig small intestine.
AB  - Serotonin neurons are descending interneurons in the myenteric plexus of the
      guinea pig small intestine. Preembedding single- and double-label
      immunocytochemistries at the ultrastructural level were used to identify the
      targets of these serotonin interneurons. Serial ultrathin sections were taken
      through a myenteric ganglion that had been processed for serotonin
      immunocytochemistry. The ganglion contained the cell bodies of 69 neurons,
      including 2 serotonin neurons and 6 neurons with the ultrastructural features of
      Dogiel type II cells. For each cell body in the ganglion, the number of serotonin
      inputs (synapses and close contacts) was determined. About 59% of the cell bodies
      did not receive any serotonin inputs. The most abundant serotonin terminals were
      related to two targets: other serotonin descending interneurons and a population
      of neurons with Dogiel type I morphology, but whose neurochemistry and function
      is unknown. The serotonin inputs to the serotonin cell bodies were located
      predominantly on the lamellar dendrites. Each of the Dogiel type II neurons
      received 3 or fewer serotonin inputs, and none of the serotonin inputs to Dogiel
      type II neurons formed a synapse. Overall, about 40% of the serotonin inputs
      formed synapses. The serotonin inputs to neurons that received many serotonin
      inputs were more likely to show synaptic specializations than serotonin inputs to
      neurons that received few serotonin inputs. Inhibitory motor neurons contain
      nitric oxide synthase (NOS). At the light microscope level, serotonin nerve
      fibers do not form dense pericellular baskets around NOS cell bodies. To
      determine whether there are serotonin inputs to NOS neurons, serial ultrathin
      sections were taken through a myenteric ganglion that had been processed for
      preembedding double-label immunocytochemistry, in which the NOS neurons were
      labeled with peroxidase-diaminobenzidine and the serotonin neurons with silver
      intensified 1 nm gold. Only 1 out of 9 NOS cells examined in serial section
      received more than 5 serotonin inputs. The results suggest that, in the guinea
      pig small intestine, the serotonin descending interneurons are not an essential
      element of the descending inhibitory reflex.

PMID- 7629307
TI  - AII amacrine cell population in the rabbit retina: identification by parvalbumin
      immunoreactivity.
AB  - Parvalbumin (PV) is a calcium-binding protein localized to selected neurons in
      the nervous system, including the retina. This investigation evaluated the
      distribution of PV immunoreactivity in the rabbit retina using
      immunohistochemistry with a monoclonal antibody directed to carp PV. In the inner
      nuclear layer (INL), PV immunoreactivity was present in horizontal and amacrine
      cells. In the ganglion cell layer, PV immunostaining was confined to somata that
      are likely to be both displaced amacrine cells and ganglion cells. PV
      immunoreactive (IR) amacrine cells were positioned in the proximal INL adjacent
      to the inner plexiform layer (IPL). These cells usually gave rise to a single
      primary process, which arborized into two distinct bands in the IPL. In sublamina
      a, the processes were thin and had large, irregular endings. In sublamina b,
      multiple processes branched from the primary process and were characterized by
      varicosities and spines. PV-IR amacrine cell bodies measured from 8 to 10 microns
      in diameter. Their density was highest in the visual streak and lowest in the
      periphery of the superior retina. The average number of PV-IR amacrine cells was
      464,045 cells per retina (N = 3), and the average regularity index of the PV-IR
      cell mosaic was 3.23. PV-IR amacrine cells were further characterized by double
      label immunofluorescence experiments using antibodies to PV and tyrosine
      hydroxylase (TH). Varicose TH-IR processes were in close apposition to many PV-IR
      amacrine cells and often formed "ring structures" around them. Together, these
      morphological, quantitative, and histochemical observations indicate that PV
      immunoreactivity in the INL is localized predominantly to AII amacrine cells, and
      therefore it is a valuable marker for the identification of this cell type.

PMID- 7629308
TI  - Ultrastructural localization of SNAP-25 within the rat spinal cord and peripheral
      nervous system.
AB  - Synaptosomal associated protein of 25 kDa (SNAP-25) has been implicated in the
      membrane fusion machinery of neurotransmitter release and axonal growth. Using
      immunocytochemistry, we have analyzed the distribution and ultrastructural
      localization of SNAP-25 in selected areas of the central and peripheral nervous
      systems of adult rats. We show that the protein is specifically expressed in the
      trans face of the Golgi apparatus and in the axonal compartment. In axons and
      nerve endings, SNAP-25 is localized to discrete areas of the membranes of most
      organelles such as the axoplasmic reticulum, the axolemma, the outer membrane of
      mitochondria and synaptic vesicles. This wide distribution of SNAP-25 suggests
      that the protein is involved in the fusion of membranes in the whole axonal
      compartment of neurons.

PMID- 7629309
TI  - Zonal organization of the flocculovestibular nucleus projection in the rabbit: a
      combined axonal tracing and acetylcholinesterase histochemical study.
AB  - With the use of retrograde transport of horseradish peroxidase we confirmed the
      observation of Yamamoto and Shimoyama ([1977] Neurosci Lett. 5:279-283) that
      Purkinje cells of the rabbit flocculus projecting to the medial vestibular
      nucleus are located in two discrete zones, FZII and FZIV, that alternate with two
      other Purkinje cell zones, FZI and FZIII, projecting to the superior vestibular
      nucleus. The retrogradely labeled axons of these Purkinje cells collect in four
      bundles that occupy the corresponding floccular white matter compartments, FC1-4,
      that can be delineated with acetylcholinesterase histochemistry (Tan et al.
      [1995a] J. Comp. Neurol., this issue). Anterograde tracing from small injections
      of wheat germ agglutin-horseradish peroxidase in single Purkinje cell zones of
      the flocculus showed that Purkinje cell axons of FZII travel in FC2 to terminate
      in the medial vestibular nucleus. Purkinje cell axons from FZI and FZIII occupy
      the FC1 and FC3 compartments, respectively, and terminate in the superior
      vestibular nucleus. Purkinje cell axons from all three compartments pass through
      the floccular peduncle and dorsal group y. In addition, some fibers from FZI and
      FZII, but not from FZIII, arch through the cerebellar nuclei to join the
      floccular peduncle more medially. No anterograde tracing experiments were
      available to determine the projections of the FZIV and C2 zones. The functional
      implications of these results are discussed.

PMID- 7629310
TI  - Immunocytochemical localization of sGnRH and cGnRH-II in the brain of goldfish,
      Carassius auratus.
AB  - The immunocytochemical distribution of salmon gonadotropin-releasing hormone
      (sGnRH) and chicken GnRH-II (cGnRH-II) neurons in the brain of goldfish was
      examined using respective antisera. Salmon GnRH-immunoreactive (ir) cell bodies
      were localized in the area between the olfactory nerve and the olfactory bulb
      (the terminal nerve ganglion), the ventral telencephalon, the preoptic area, and
      the hypothalamus. Chicken GnRH-II-ir cell bodies were observed in the same areas
      as were those of sGnRH, although the number of cell bodies were fewer than those
      of sGnRH. In addition, chicken GnRH-II-ir cell bodies were also observed in the
      midbrain tegmentum where no sGnRH-ir cell bodies were found. Both sGnRH-ir and
      cGnRH-II-ir fibers were distributed not only in the hypothalamus and the
      pituitary gland but also in various brain areas from the olfactory bulb to the
      spinal cord. The wide distribution of GnRH-ir fibers suggests that in the
      goldfish, sGnRH and cGnRH-II not only regulate gonadotropin release from the
      pituitary gland but also function as neuromodulators in various brain regions.

PMID- 7629312
TI  - Of hearts and minds: natriuretic peptides in the brain.

PMID- 7629311
TI  - Accumulation of neuropeptides in the cerebral neurosecretory system of Manduca
      sexta larvae parasitized by the braconid wasp Cotesia congregata.
AB  - Fifth instar larvae of Manduca sexta that were parasitized by the braconid wasp
      Cotesia congregata failed to develop after the parasitoid larvae emerged, and
      these host larvae lingered for 2-3 weeks in a quiescent, nonfeeding state without
      initiating a larval molt or metamorphosis. This study was focused on the
      neuroendocrine changes associated with the host's developmental arrest.
      Immunohistochemical studies suggested that the host brain neurosecretory cells as
      well as their axon terminals in the corpora cardiaca-corpora allata complex
      accumulated multiple neuropeptides. The extent of accumulation in cells and axons
      increased with time, so that hosts examined 7-14 days after the wasps emerged
      showed the most intense staining with antibodies against prothoracicotropic
      hormone, bombyxin, allatotropin, allatostatin, diuretic hormone, eclosion
      hormone, proctolin, and FMRFamide. Increased levels of prothoracicotropic hormone
      and FMRFamide-like peptides in the brains of parasitized larvae were confirmed
      using Western blots and enzyme-linked immunosorbent assay (ELISA), respectively.
      Starvation of the unparasitized larvae induced some accumulation of the
      neuropeptides; however, the intensity of staining and number of immunopositive
      cells and axons were in most cases clearly higher in the parasitized larvae. Our
      results suggest that accumulation of the neuropeptides is associated with
      developmental arrest of parasitized larvae. Because a similar developmental
      arrest occurs in a wide range of parasitized insects, our findings may have
      relevance for many other species. Moreover, these data illustrate the potential
      value of using parasitized M. sexta larvae as a model for studying the mechanisms
      governing the rates of neuropeptide expression, processing, packaging, and
      release, as well as providing a rich source of neuropeptides, thus facilitating
      their isolation and characterization.

PMID- 7629313
TI  - Anatomical localisation of preproatrial natriuretic peptide mRNA in the rat brain
      by in situ hybridisation histochemistry: novel identification in olfactory
      regions.
AB  - Atrial natriuretic peptide (ANP) is one of three structurally homologous
      natriuretic peptides present in heart and brain, which is thought to be involved
      in the regulation of water and salt intake, blood pressure, and hormone
      secretion. In the present study, the distribution of preproatrial natriuretic
      peptide (ppANP) mRNA in the central nervous system of the rat was examined by in
      situ hybridisation histochemistry by using [35S]-labelled oligonucleotides. Cells
      expressing ppANP mRNA were apparent in several major neuronal systems, being
      present in hypothalamic, limbic, pontine and forebrain olfactory regions.
      Relatively high densities of ppANP mRNA-positive neurones were found in the
      anterior medial preoptic hypothalamic nucleus, medial habenular nucleus, and in
      Barrington's nucleus in the pons. Moderate numbers of ppANP mRNA-positive cells
      were present in a number of amygdaloid nuclei, including the posterolateral and
      anterior cortical nuclei, in the zona incerta, and the pedunculopontine tegmental
      nucleus. Other areas, including the ventromedial hypothalamic nucleus and the
      laterodorsal tegmental nucleus, displayed only low densities of ppANP mRNA
      positive neurones. A number of structures in which ppANP mRNA (or ANP-like
      immunoreactivity) has not previously been reported were found to contain moderate
      to high numbers of ppANP mRNA-positive neurones including several nuclei
      associated with the olfactory system, such as the anterior olfactory nucleus and
      neurones of the tenia tecta and ventrolateral orbital cortex. Although ppANP mRNA
      in CA1 pyramidal cells of the hippocampus has been described, we also detected
      labelling in CA2 and ventral CA3 regions of the hippocampus. Conversely, nuclei
      such as the bed nucleus of the stria terminalis and the nucleus of the solitary
      tract, which are reported to possess ANP-like immunoreactivity, were found not to
      contain ppANP mRNA. Overall, these results demonstrate the presence of ANP gene
      expression in discrete neuronal populations of the rat central nervous system and
      provide additional evidence to support a putative role for this peptide in
      regulating and integrating hypothalamic, olfactory, limbic, and neuroendocrine
      systems.

PMID- 7629314
TI  - Distribution of natriuretic peptide precursor mRNAs in the rat brain.
AB  - Atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type
      natriuretic peptide (CNP) represent members of a recently discovered neuropeptide
      family involved in central regulation of endocrine and autonomic functions. The
      present study employed an in situ hybridization approach to provide the first
      detailed comparative mapping of ANP, BNP, and CNP mRNAs in brain. Results
      indicate that ANP mRNA is highly expressed in anterior olfactory nuclei, limbic
      cortices, dorsal endopiriform nucleus, hippocampal subfield CA1, cortical
      amygdaloid nuclei, medial habenula, anteroventral periventricular and arcuate
      nuclei, periventricular stratum, zona incerta, mammillary nuclei, inferior olive,
      nucleus ambiguus, and pontine paragigantocellular nuclei. CNP mRNA is expressed
      at highest levels in olfactory nuclei, limbic cortices, dorsal endopiriform
      nucleus, hippocampal subfields CA1-3, anteroventral periventricular and arcuate
      nuclei, and numerous brainstem regions (including the pontine, lateral reticular,
      solitary tract, prepositus hypoglossal, and spinal trigeminal nuclei). Positive
      labeling for BNP mRNA was not observed in brain. The presence of both ANP and CNP
      mRNA in the same regions of distinct nuclei (e.g., the anteroventral
      periventricular and arcuate nuclei) suggests the potential for coexpression.
      Overall, the present data are consistent with a prominent role for both ANP and
      CNP in neuroendocrine regulation and central cardiovascular integration. The
      extensive localization of ANP and/or CNP mRNA in olfactory nuclei, limbic cortex,
      hippocampus, amygdala and diencephalic limbic relays further indicate a putative
      role for ANP and CNP as neuromodulators of olfactory/limbic information
      processing.

PMID- 7629315
TI  - Structure-function relationships in rat brainstem subnucleus interpolaris. XI.
      Effects of chronic whisker trimming from birth.
AB  - Whisker trimming from birth reduces activity and alters receptive fields (RFs) in
      the barrel cortex and thalamus. To assess whether or not this reflects
      deprivation effects on trigeminal (V) first- and second-order neurons, 59 primary
      afferents and 343 cells in V brainstem subnucleus interpolaris (SpVi) were
      studied in rats whose whiskers were trimmed daily for 6-9 weeks from birth.
      Deprivation did not effect brainstem somatotopy or primary afferent RFs. However,
      many SpVi cells had abnormal RFs and higher-order inputs, resembling the changes
      caused by infraorbital nerve injury. For example, in controls, only 3% of whisker
      sensitive local circuit neurons responded to more than one whisker, whereas 35%
      of the deprived and 41% of the infraorbital nerve cut samples had multiwhisker.
      RFs. Deprived rats also had higher than normal incidences of cells with split or
      absent RFs, RFs spanning more than one V division, intermodality convergence, and
      directional or high-velocity sensitivity. Because these changes mimic those
      caused by nerve section, deprivation may underlie some nerve injury effects on V
      brainstem RF size and character. Insofar as cytochrome oxidase, anterograde
      labeling, and unit recordings revealed normal topography in deprived primary
      afferents and SpVi cells, RF changes in SpVi cells may reflect altered SpVi
      circuitry. To test this hypothesis, we assessed the morphology of 32 similarly
      deprived V primary afferents. In SpVi, deprived fibers had normal numbers of
      collaterals with normal shapes, transverse arbor areas, and topography. However,
      the total number of boutons per collateral was significantly reduced. Thus,
      deprivation effects on V higher-order RFs reflect quantitative changes in V
      afferent terminals.

PMID- 7629316
TI  - Motoneurons dorsolateral to the central canal innervate perineal muscles in the
      Mongolian gerbil.
AB  - The Mongolian gerbil provides a model in which sexually dimorphic areas in the
      hypothalamus are correlated with sociosexual behaviors such as scent marking and
      male copulatory behavior. To extend this model, investigations were conducted to
      determine whether sexually dimorphic areas existed in the spinal cord that could
      be relevant to male sexual behavior. The focus of these investigations was the
      perineal muscles associated with the penis. Therefore, this research identified
      the spinal motoneurons that innervate the bulbocavernosus, levator ani, anal
      sphincter, and ischiocavernosus muscles of Mongolian gerbils. The motoneuron pool
      that innervates the bulbocavernosus, levator ani, and anal sphincter was
      designated the spinal nucleus of the bulbocavernosus (SNB), as for other species
      of rodents. The motoneuron pool innervating the ischiocavernosus was identified
      as the dorsolateral nucleus, again, to be consistent with the designation for
      other rodents. The motoneurons of the gerbil SNB were distributed dorsolateral to
      the central canal in the lumbosacral transition zone of the spinal column. These
      motoneurons are located in the region classically defined as area X of the spinal
      cord. The number of SNB motoneurons was sexually dimorphic, with male gerbils
      having about five times as many SNB motoneurons as do female gerbils. The size of
      SNB motoneurons was also sexually dimorphic. The SNB motoneurons of males were
      1.5 times larger than the SNB motoneurons of females. The effects of adult
      castration on the male SNB were also studied. After castration, the size, but not
      the number, of SNB motoneurons in males was significantly decreased. This
      decrease was prevented by testosterone treatment. The percentage of calcitonin
      gene-related peptide (CGRP)-immunoreactive SNB motoneurons was also affected by
      adult castration. The percentage of CGRP-immunoreactive motoneurons was
      significantly decreased after adult castration. Again, this decrease was reversed
      by testosterone treatment. These findings suggest that the SNB of gerbils is
      sexually dimorphic and is sensitive to circulating levels of gonadal steroids.
      The unique placement of the SNB motoneurons suggests that an alternative laminar
      organizational scheme may be necessary for Mongolian gerbil.

PMID- 7629317
TI  - Distribution of calcium-binding proteins within the parallel visual pathways of a
      primate (Galago crassicaudatus).
AB  - Bush babies possess three distinct parallel pathways to striate cortex (V1 or
      area 17). The calcium-binding proteins parvalbumin (PV) and calbindin (CB)
      typically show complementary regional distributions in the brain, often
      associated with specific aspects of functionally related groups of cells. We
      asked whether PV+ and CB+ immunoreactivity differentiate central visual parallel
      pathways in this species. Results show that PV and CB cell and neuropil staining
      is strongly complementary in the lateral geniculate nucleus (LGN) and is
      associated with separate parallel pathways. CB+ immunoreactivity is dense, but
      cytochrome oxidase (CO) staining is light in the paired koniocellular layers. PV+
      and CO+ immunoreactivity is most dense in the parvocellular and magnocellular
      layers. Combined analyses of cell size, retrograde labeling, and double labeling
      have confirmed that all PV+ and CB+ LGN cells are geniculocortical relay cells;
      none was found to be gamma-aminobutyric acid (GABA)ergic. In V1, dense PV+
      neuropil closely matches the expression of CO in layer 4 and in the blobs of
      layer 3. CB+ staining is most dense in layers 2 and 3A and is not strongly
      expressed within the CO interblobs. Finally, PV and CB are not found in related
      parallel pathway components in the LGN and V1 (e.g., in V1, CO blobs exhibit
      dense PV+ neuropil, yet they are targets of the small K geniculocortical relay
      cells that are CB+ in the LGN). Our findings support the view that three
      functionally distinct visual pathways project to V1 from the LGN. However, the
      differences in the patterns of localization of PV and CB in the LGN and in V1
      suggest that these proteins may be utilized in different ways in these two visual
      areas.

PMID- 7629318
TI  - Localization of nicotinamide adenine dinucleotide phosphate-diaphorase activity
      in electrosensory and electromotor systems of a gymnotiform teleost, Apteronotus
      leptorhynchus.
AB  - The distribution of nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH
      d) activity was determined in electrosensory and electromotor systems of the
      weakly electric gymnotiform teleost Apteronotus leptorhynchus as an indicator of
      putative nitric oxide synthase-containing cells. NADPH-d activity was detected in
      electroreceptors and in afferent nerves of both ampullary and type I and type II
      tuberous organs. All cell bodies within the anterior lateral line nerve ganglion
      were positive for NADPH-d activity, as were the primary afferent axons and
      termination fields in the medullary electrosensory lateral line lobe. In the
      corpus cerebelli and valvula cerebelli, NADPH-d label was present in Purkinje
      cell somata, mossy fiber synaptic glomeruli, granule cells, and parallel fibers.
      In the midbrain, NADPH-d activity was apparent in layer VIIIB of the torus
      semicircularis dorsalis and in electrosensory laminae of the optic tectum. NADPH
      d was particularly associated with diencephalic electrosensory and electromotor
      nuclei, including the prepacemaker nucleus, the nucleus subelectrosensorius, and
      the central posterior nucleus of the thalamus. Intense NADPH-d activity was
      present in pacemaker and relay cells of the medullary pacemaker nucleus but was
      absent from a novel class of smaller cells in this structure. Relay cell axons
      and spinal electromotor neurons and their axons within the electric organ were
      positive for NADPH-d activity. These results indicate that putative nitric oxide
      synthase-containing neurons in Apteronotus are localized preferentially to
      electrosensory and electromotor structures, suggesting a role for nitric oxide in
      determining the activity of cells involved in detecting or generating weakly
      electric fields.

PMID- 7629319
TI  - Octopamine immunoreactivity in the fruit fly Drosophila melanogaster.
AB  - Octopamine has been proposed as a neurotransmitter/modulator/hormone serving a
      variety of physiological functions in invertebrates. We have initiated a study of
      octopamine in the fruit fly Drosophila melanogaster, which provides an excellent
      system for genetic and molecular analysis of neuroactive molecules. As a first
      step, the distribution of octopamine immunoreactivity was studied by means of an
      octopamine-specific antiserum. We focused on the central nervous system (CNS) and
      on the innervation of the larval body wall muscles. The larval octopamine
      neuronal pattern was composed of prominent neurons along the midline of the
      ventral ganglion, whereas brain lobes were devoid of immunoreactive somata.
      However, intense immunoreactive neuropil was observed both in the ventral
      ganglion and in the brain lobes. Some of the immunoreactive neurons sent
      peripheral fibers that innervated most of the muscles of the larval body wall.
      Octopamine immunoreactivity was observed at neuromuscular junctions in all larval
      stages, being present in a well-defined subset of synaptic boutons, type II.
      Octopamine immunoreactivity in the adult CNS revealed many additional neurons
      compared to the larval CNS, indicating that at least a subset of adult octopamine
      neurons may differentiate during metamorphosis. Major octopamine-immunoreactive
      neuronal clusters and neuronal processes were observed in the subesophageal
      ganglion, deutocerebrum, and dorsal protocerebrum, and intense neuropil staining
      was detected primarily in the optic lobes and in the central complex.

PMID- 7629320
TI  - Intrinsic connections of the rat amygdaloid complex: projections originating in
      the lateral nucleus.
AB  - The amygdaloid complex receives sensory information from a variety of sources. A
      widely held view is that the amygdaloid complex utilizes this information to
      orchestrate appropriate species-specific behaviors to ongoing experiences.
      Relatively little is known, however, about the circuitry through which
      information is processed within the amygdaloid complex. The lateral nucleus is
      the major recipient of extrinsic sensory information and is the origin of many
      intra-amygdaloid projections. In this study, we reinvestigated the organization
      of intra-amygdaloid projections originating from the lateral nucleus using the
      anterograde tracer Phaseolus vulgaris leucoagglutinin (PHA-L). The lateral
      nucleus has highly organized intranuclear connections. Dense projections
      interconnect rostral and caudal levels of the lateral and the medial divisions of
      the nucleus, and the lateral and medial divisions of the lateral nucleus are also
      interconnected. The major extranuclear projections of the lateral nucleus are (in
      descending order of magnitude) to the accessory basal nucleus, the basal nucleus,
      the periamygdaloid cortex, the dorsal portion of the central division of the
      medial nucleus, the posterior cortical nucleus, the capsular division of the
      central nucleus, and the lateral division of the amygdalohippocampal area. The
      pattern of extranuclear projections varied depending on the rostrocaudal or
      mediolateral location of the injection site within the lateral nucleus. These
      findings indicate that intra-amygdaloid projections originating in the lateral
      nucleus are both more widespread and more topographically organized than was
      previously appreciated.

PMID- 7629321
TI  - Expression of neurofilament proteins during development of the nervous system in
      the squid Loligo pealei.
AB  - The squid nervous system includes various brain ganglia, optic lobes (the visual
      center), and the stellate ganglia, the system of giant motor fibers responsible
      for rapid jet-propelled escape behavior. The large caliber of giant fibers is
      due, in part, to the accumulation of squid-specific neurofilaments (NFs) made up
      of a heavily phosphorylated NF 220 protein together with NF 70 and NF 60
      subunits. Using antibodies prepared against known peptide sequences in these
      proteins, together with a mammalian-derived antibody that specifically recognizes
      phosphorylated squid NF 220, we studied the localization of NFs in adult tissues
      and during neural development. Immunoblot and immunohistochemical analyses showed
      that NFs were present in adult neural tissues, primarily in selected fibers, with
      giant axons showing the most robust expression. After the first neurons
      differentiated at stage 22, immunoblots showed NF 60- and NF 70-immunoreactive
      proteins at all stages. The NF 220 subunit, however, was not detected in
      immunoblots at any developmental stage. Phosphorylated NF 220 immunoreactivity,
      although absent in immunoblots, was first seen in selected fibers of the stellate
      ganglia at stage 25, increasing thereafter in all giant fibers until hatching
      (stage 30). The stellate ganglion is the first neural tissue to acquire a mature
      neurofilament complement (i.e., phosphorylated NF 220), shortly before the onset
      of jet-propelled escape behavior. The temporal pattern of expression of the NFs
      during development resembled that seen in vertebrates; i.e., the smaller NFs
      appeared before the larger subunit in most neural tissues. In the squid, the
      expression pattern seems to depend upon the post-transcriptional regulation of a
      single gene rather than upon transcriptional regulation of three independent
      genes as in vertebrates.

PMID- 7629322
TI  - An improved reagent for chemomechanical caries removal in permanent and deciduous
      teeth: an in vitro study.
AB  - OBJECTIVES AND METHODS: An in vitro study has been carried out on the
      chemomechanical removal of caries in deciduous and permanent teeth. The aims of
      the study were to compare the efficacy of caries removal by various chemical
      agents including N-monochloro-DL-2-aminobutyrate (NMAB) and NMAB containing urea
      (NMAB-urea), to compare the efficacy on permanent and deciduous teeth and to
      study the dentinal surfaces produced. RESULTS: The addition of urea to NMAB
      resulted in an improvement in the efficacy of caries removal. Sodium
      hypochlorite, saline and urea alone were also studied as caries removal agents,
      but were not significantly different from NMAB. Chemomechanical caries removal
      solutions were more effective in removing caries from deciduous teeth than from
      permanent teeth, especially in terms of the volume of solution used. The
      improvement on addition of urea was found to be greater in deciduous than in
      permanent teeth, the number of deciduous teeth with 'complete cares removal'
      being increased by about 25%. The dentinal surfaces of the cavities prepared
      using these solutions and in which 'complete caries removal' had been achieved
      were studied by scanning electron microscopy. Generally after treatment with NMAB
      or NMAB-urea, the surface appearance was very uneven with many undermined areas.
      NMAB-urea produced a 'cleaner' surface compared with that produced by NMAB alone.
      CONCLUSIONS: NMAB appears to be potentially more effective and clinically more
      useful in removing caries in deciduous teeth than in permanent teeth, and the
      addition of urea may enhance its efficacy, especially in the treatment of
      paediatric dental patients.

PMID- 7629323
TI  - Digitizing of radiographs with a flatbed scanner.
AB  - OBJECTIVES: Flatbed scanners with the transparency scanning option can be used to
      digitize radiographs. The physical performance of this type of scanner was
      studied with regard to the digitizing of radiographs, including the dynamic
      range, the reproducibility and the homogeneity. METHODS: An Artix ArtiScan (Artix
      Technologies Inc., Milpitas, CA, USA) flatbed scanner with imaging editing
      software Aldus PhotoStyler (Aldus Corporation, Seattle, WA, USA) was used to
      digitize a stepped exposure image on Kodak T-MAT G films (Kodak, Rochester, NY,
      USA). The stepped exposure image was scanned at various locations and with
      different scanning settings. The pixel values of the resulting digital images
      were analysed. The stepped exposure image was also scanned by a laser
      densitometer to measure the optical densities of the steps on the film for
      comparison. RESULTS: Using the default scanning settings, the digitized images
      had pixel values distributed in a narrower range than that of the optical density
      values of the films. The range of the pixel values was widened by increasing the
      scanning time. Even then, the resulting pixel value profile was not identical to
      the optical density profile measured on film. The characteristic curve of this
      digitizing system was steeper than that of the film. Different pixel value
      distributions were obtained when the stepped exposure image was scanned at
      different positions on the scanning field, and when scans were obtained at
      different times. Reproducible results could be acquired when the images were
      scanned in the same area of the scanning field without changing the scanning
      settings and after the power had been on for a few minutes. CONCLUSIONS: In order
      to obtain digitized radiographs of any reliability from flatbed scanners, these
      should be carefully calibrated at the operating conditions.

PMID- 7629324
TI  - Salivary clearance of citric acid after an oral rinse.
AB  - OBJECTIVES: Citric acid clearance from the oral cavity may be an important factor
      in the erosion of dental enamel. The aim of the present study was to investigate
      the clearance pattern of citric acid in normal subjects. METHODS: After
      determination of the unstimulated salivary flow rate and the residual volume of
      saliva after normal swallowing, 12 subjects rinsed with 95.2 mmol l-1 citric acid
      for 5 s. At 1, 2, 5, 10 and 15 min after the rinse a small saliva sample was
      collected and the concentration of citric acid was determined enzymatically. For
      each subject three separate experiments on different occasions were performed
      with a citric acid solution of pH 2.1 and one experiment with a solution of pH
      4.5. RESULTS: The salivary citric acid concentration declined biphasically:
      rapidly during the first 2 min, then more slowly. The elimination rate over the
      first minute was on average 87.7 mmol l-1 min-1 at pH 2.1 compared with 85.0 mmol
      l-1 min-1 at pH 4.5. The difference between individuals estimated from the areas
      under the clearance curve was strongly significant (P < 0.001). No significant
      relation was found neither between salivary flow rate and clearance, nor between
      residual volume after swallowing and clearance. CONCLUSION: The clearance pattern
      of citric acid is an individual property.

PMID- 7629325
TI  - Tunnel restorations: a long-term pilot study over a minimum of five years.
AB  - OBJECTIVES: The purpose of this study was to investigate the long-term
      performance of tunnel restorations. METHODS: Thirty-three glass polyalkenoate
      (ionomer) or cermet restorations were placed in the premolar or first molar teeth
      of 25 patients. Conservative amalgam control restorations were the means of
      treatment in 14 similar teeth of the same group. Review as to performance
      consisted of a regular clinical and radiographic examination and the criteria for
      failure were recurrent caries, fracture of the marginal ridge or gross loss of
      restorative material. RESULTS: After 3 years all types of restoration were
      satisfactory. By approximately 5 years one-quarter of the glass ionomer and 10%
      of the cermet restorations had failed. All the failures after any period of
      service could be replaced by conservative amalgam fillings. None of the controls
      required replacement. CONCLUSION: While tunnel restorations employing glass
      ionomer material and the cermet variant do enjoy a degree of success, this
      preliminary work suggests that small restorations of dental amalgam are more
      successful in the long term.

PMID- 7629326
TI  - Dentine permeability and bond quality as affected by new bonding systems.
AB  - OBJECTIVES AND METHODS: The relationship between dentine bonding and the
      condition of dentine for four dentine bonding systems (All Bond 2, Clearfil Liner
      Bond, Scotchbond MP and XR Bond) has been examined. Different dentine conditions
      were evaluated and correlated with adhesion values. Dentine permeability was
      calculated using a hydraulic pressure apparatus working under physiological
      pulpal pressure (6.9 kPa), while remaining dentine thickness (RDT) was measured
      using pincer calipers. Scanning electron microscopic (SEM) examinations were
      effected to analyse dentine morphology. These evaluations were considered as an
      index of the condition of dentine. Shear bond strength tests were used to
      evaluate adhesion. Dentine samples after the bonding systems application were
      stored for 24 h under pulpal pressure before bond strength was tested. RESULTS:
      Scanning electron microscopy examinations indicated that the application of
      bonding system conditioners caused the removal of smear layer, the
      demineralization of dentine and the formation of a layer of collapsed collagen
      fibrils in the intertubular and peritubular dentine. Primers were able to
      infiltrate the collagen fibrils. A layer of resin infiltrated/reinforced dentine
      (the so-called 'hybrid layer') was observed for All Bond 2, Clearfil Linear Bond
      and Schotchbond MP. CONCLUSIONS: Significant correlations were observed only for
      XR Bond, which proved very sensitive to RDT and dentine permeability despite the
      presence of smear layer. The other three materials did not show any correlation
      with dentine conditions. By contrast they showed the highest bond values.

PMID- 7629327
TI  - Light curing unit effectiveness assessed by dental radiometers.
AB  - OBJECTIVES: The purpose of this investigation was to assess the effectiveness of
      five commercially available hand-held dental radiometers and a computer-based
      experimental radiometer. METHODS: Light intensity of five visible light
      activation units was determined using the dental radiometers. The influence of
      curing light intensity on depth of cure of a hybrid composite material was
      determined using a digital penetrometer. RESULTS: The radiometers evaluated
      varied with respect to sensor aperture diameter, scale readings (analogue or
      digital) and the units of measurement (arbitrary or mW cm2). The experimental
      computer-based radiometer allowed continuous recording of intensity against time;
      thus the light output could be monitored over the entire irradiation period.
      CONCLUSIONS: When light intensity readings were normalized with regard to a
      standardized light sensing device aperture of 4 mm diameter, a linear
      relationship was found between depth of cure and the logarithm of the intensity
      of the light. The results of this investigation support the use of dental
      radiometers for periodically monitoring visible light activation units.

PMID- 7629328
TI  - Release of fluoride from glass polyalkenoate (ionomer) cement subjected to
      radiant heat.
AB  - OBJECTIVES: This study was designed to examine the effect of the application of
      radiant heat on the fluoride release from the surface of a glass polyalkenoate
      cement. METHODS: The radiant heat was applied at different intensities and for
      different time intervals using a high-intensity fibreoptic quartz halogen light
      source. A standard technique was used to measure the amount of fluoride released
      from one surface of a cement specimen into deionized water. Fluoride release was
      measured for a time period of over 2 years. RESULTS: Results showed that fluoride
      was still being released 2 years after placement. The application of radiant heat
      did not have a statistically significant effect on the release of fluoride from
      the surface of this material. CONCLUSIONS: There appeared to be a trend
      suggesting that the greater the amount of heat applied, the less fluoride was
      released from the surface of the cement. A considerable inter- and intrabatch
      variation was noted in the amount of fluoride released from the cement.

PMID- 7629329
TI  - Casting shrinkage of thin-walled castings.
AB  - OBJECTIVES AND METHODS: The casting shrinkage of thin-walled castings was
      measured using a tungsten die method. The thickness and the surface area of the
      casting were simulated to those of either partial veneer crowns or complete
      denture frameworks. Gold alloys were cast at two different pressures (0.35 and
      0.49 MPa) and the shrinkage measurement was made at different locations on the
      castings to investigate the effect of these factors. RESULTS: Both overall and
      local shrinkages were significantly influenced by size and casting pressure.
      These shrinkages were significantly lower for the denture-sized (DS) specimens
      than for the crown-sized (CS) specimens, and significantly decreased with the
      increase of the casting pressure. The effect of location on the local shrinkage
      significantly varied with the change of the other two factors, size and pressure.
      At the higher casting pressure, the DS specimens sustained a significantly
      smaller shrinkage at the margin than at the centre, whereas the CS specimens had
      a significantly smaller shrinkage at the centre than at the margin at the lower
      pressure. CONCLUSIONS: The results suggest that the casting shrinkage of a thin
      walled casting is influenced by the temperature gradient in the alloy and the
      resultant time difference in alloy solidification as well as the volume supply of
      the molten alloy in the mould.

PMID- 7629330
TI  - Temperature and dimensional changes in the two-stage processing technique for
      complete dentures.
AB  - OBJECTIVES: This study concerned the temperature and linear dimensional change of
      heat-cured acrylic resin in the two-stage processing technique for complete
      dentures. METHODS: Thermocouples were incorporated in the acrylic resin for
      recording temperatures. Measurements between reference marks were made by a high
      resolution digital measuring microscope. RESULTS: No increase in temperature
      associated with the exothermic nature of the polymerization reaction was
      recorded. The temperature of the resin followed the waterbath temperature
      closely. The temperatures recorded at various regions were in phase with each
      other. The total linear shrinkage of the base after two processing cycles was
      less than 1% and compares favourably with studies on the single-stage processing
      technique. CONCLUSIONS: Temperature differential is excluded as a reason for the
      warpage of dentures. The dimensional changes of the denture base resulting from
      the two-stage processing technique cannot be considered to be of any clinical
      significance.

PMID- 7629331
TI  - Mechanical behaviour and structure of light-cured special tray materials.
AB  - OBJECTIVES: This study relates some structural characteristics of representative
      special tray visible light cured (VLC) resin composites to their creep-recovery,
      hardness and flexural strength properties. VLC prosthodontic materials have not
      yet achieved the same acceptance as the VLC resin composites, perhaps because
      less is known of their structural and performance characteristics. METHODS: The
      VLC resin composites used were Triad, Convertray and Palatray. The inorganic
      composition was analysed quantitatively by heating known amounts of resin
      composite to 800 degrees C, and weighing the ash. Elemental composition was
      determined using X-ray microanalysis. Mechanical properties, including hardness,
      flexural behaviour and creep recovery, were obtained by standard methods.
      RESULTS: The inorganic filler content for Palatray was higher than that of
      Convertray or Triad, and the flexural modulus and flexural strength of Palatray
      were superior to that of Triad or Convertray. The mean maximum creep strain for
      the Palatray specimens was only 2.45% after 5 h loading under 37 MPa and there
      was a permanent set of 1.5% after 7 h recovery. CONCLUSIONS: Palatray exhibited
      superior overall properties and this evidently related primarily to the high
      volume fraction of filler.

PMID- 7629333
TI  - Failure of all-ceramic fixed partial dentures in vitro and in vivo: analysis and
      modeling.
AB  - Hertzian cone cracks visible at the loading site of 20 all-ceramic fixed partial
      dentures (FPDs), tested in vitro, led to the hypotheses that failure was due to
      the propagation of localized contact damage crack systems (Hertzian stress state)
      and that such damage was an unlikely clinical failure mode. Fractographic
      analysis of the 20 laboratory-failed and nine clinically-failed all-ceramic FPDs
      allowed for definitive testing of these hypotheses and a comparison between in
      vitro and in vivo failure behavior. In all cases, failure occurred in the FPD
      connectors (none from contact damage), with approximately 70 to 78% originating
      from the interface between the core and veneer ceramics. The coincidence between
      failure origins provides strong evidence that the in vitro test modeled aspects
      of structural behavior having clinical importance. The fractographic
      observations, coupled with the in vitro failure load data, furnished very
      specific boundary conditions which were applied to constrain mathematical models
      of FPD connector failure. Finite element analysis (FEA) of the laboratory FPDs
      found that maximum principal tensile stresses would occur at locations consistent
      with the fractographic observations only if: (1) there were appropriate elastic
      moduli differences between the ceramics; and (2) a small amount of abutment
      rotation was allowed. Weibull failure probability (Pf) calculations,
      incorporating FEA stress profiles, very closely replicated the laboratory failure
      distribution only when: (1) the veneer ceramic was much weaker than the core
      ceramic; and (2) the Weibull modulus of the core-veneer interface was much lower
      than that for the free veneer surface (i.e., the interface is of lower quality
      with regard to defects).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7629332
TI  - Scanning transmission electron microscopy/energy-dispersive spectroscopy analysis
      of the dentin adhesive interface using a labeled 2-hydroxyethylmethacrylate
      analogue.
AB  - In an attempt to compare the morphology of the dentin adhesive interface and the
      wetting and penetration of the adhesive in relation to the dentin surface, we
      studied four dentin adhesive systems using scanning transmission electron
      microscopy (STEM) and energy-dispersive spectroscopy (EDS). 2
      Hydroxyethylmethacrylate (HEMA), a monomer common to many commercial dentin
      adhesive systems, was altered to produce a thiolated analogue (HETMA). Sulfur,
      traceable by EDS and STEM, was substituted for the oxygen atom in the backbone of
      the HEMA molecule. The resulting analogue, with solubility parameters and other
      wetting and physical properties very similar to those of HEMA, was applied to
      four sets of tooth specimens, each pre-treated with a different primer or
      etchant. Three separate pre-treatments--nitric acid, maleic acid, and citric
      acid/ferric chloride--created a demineralized zone approximately 1 to 3 microns
      thick at the dentin surface. The HETMA was found to permeate freely into this
      zone when either of the latter two pre-treatments was used. However, the band of
      dentin that was demineralized by the nitric acid pre-treatment appeared
      impermeable to the HETMA. The fourth pre-treatment, an alcohol-based solution
      including the phosphorus acid ester PENTA and HEMA, modified the smear layer of
      the tooth slightly and did not appear to demineralize the dentin. HETMA applied
      to the specimens pre-treated with PENTA and HEMA was clearly in intimate contact
      with the dentin or modified smear layer; however, it did not penetrate or diffuse
      into these areas. It did flow into the dentinal tubules, as was also evident with
      each of the other systems. It was concluded that the acid pre-treatment of the
      dentin greatly influenced the wetting behavior of the dentin adhesive and thus
      could substantially affect the resultant bond strength of the dentin adhesive
      systems.

PMID- 7629334
TI  - Isothermal anneal effect on leucite content in dental porcelains.
AB  - Porcelain thermal expansion behavior is a function of leucite content, and
      leucite changes can produce porcelain-metal incompatibilities. The purpose of the
      present study was to determine whether isothermal anneal treatments (such as are
      encountered during "post-soldering" operations) could result in alterations of
      leucite content of dental porcelain. Six commercial dental porcelains and the
      "Component No. 1" frit of the Weinstein et al. patent (1962) were studied. Twenty
      eight coupon specimens of each porcelain were fired and divided randomly into
      seven groups of four specimens each. One group served as a control, while the
      other six groups were subjected to isothermal anneal treatments--three groups at
      500 degrees C and three groups at 750 degrees C, for 4, 8, and 16 min,
      respectively. Leucite volume fraction was measured via quantitative x-ray
      diffraction. From an equation for the growth of particles in competition for
      diffusing material, an expression was derived for the potential simultaneous
      processes of leucite crystallization and reaction of leucite+glass to form
      sanidine or other compounds. This exponential growth/decay curve was fit through
      the experimental data for each porcelain by minimization of the sum of the
      squares of the residuals through iteration. For each porcelain, a statistically
      significant correlation was obtained between leucite volume fraction and
      isothermal anneal duration at 750 degrees C (p < 0.01), whereas at 500 degrees C,
      only CII exhibited a statistically significant correlation (p < 0.01). The
      control (non-annealed) leucite volume fractions for the commercial porcelains
      ranged from (mean +/- SD) 0.155 +/- 0.002 for WIL to 0.442 +/- 0.003 for
      Component No. 1. The 750 degrees C isothermal anneal increased the leucite volume
      fraction by between 6.1% and 21.3%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7629335
TI  - Hypermineralization of dentinal lesions adjacent to glass-ionomer cement
      restorations.
AB  - Previous reports have shown a release of fluoride from glass-ionomer cement (GIC)
      restorations into the oral fluids. Fluoride in the ambient fluids has a caries
      preventive effect by enhancing remineralization and inhibiting demineralization
      of the dental hard tissues. Therefore, the current investigation was undertaken
      to determine whether GIC fillings could contribute to the remineralization of
      caries lesions in dentin. Small circular preparations were made in disks of
      dentin which had incipient caries-like lesions in the remaining tissue. The
      preparations were filled with amalgam or composite materials (as controls) or
      with GIC. The specimens thus contained a restoration close to a dentinal caries
      like lesion. The specimens were placed contralaterally in the buccal surfaces of
      removable partial dentures and were worn intra-orally by volunteers for a 12-week
      experimental period, after which the specimens were sectioned and analyzed by
      microradiography. All specimens with GIC restorations exhibited
      hypermineralization in the tissue bordering the filling and in the wall of the
      preparation which had been in contact with the restoration. The (caries-like)
      lesions were remineralized, even under conditions of heavy plaque formation. In
      contrast, specimens with amalgam or composite restorations showed further
      extensive demineralization. This study demonstrates a significant
      remineralization potential exerted by the fluoride-releasing GIC restorative
      material. Consequently, the choice of the restorative material might be crucial
      for the occurrence or prevention of recurrent caries around restorations.

PMID- 7629336
TI  - Anticariogenicity of calcium phosphate complexes of tryptic casein
      phosphopeptides in the rat.
AB  - Casein phosphopeptides (CPP) stabilize calcium phosphate through the formation of
      casein-phosphopeptide amorphous calcium-phosphate complexes (CPP-CP). The ability
      of CPP-CP to reduce caries activity was investigated by use of specific-pathogen
      free rats inoculated with Streptococcus sobrinus. The animals consumed a defined
      cariogenic diet free of dairy products. Solutions (100 microL) of the CPP-CP
      (0.1, 0.2, 0.5, 1.0% w/v) were applied to the animals' molar teeth twice daily.
      Other groups of animals received solutions containing 500 ppm F, the non
      phosphorylated peptides of a casein tryptic digest (0.5% w/v), or the calcium
      phosphate complex of a synthetic octapeptide, Ac-Glu-Ser(P)-Ile-Ser(P)-Ser(P)
      Ser(P)-Glu-Glu-NHMe, corresponding to the common sequence in the CPP. The CPP-CP
      significantly reduced caries activity in a dose-response fashion, with 1.0% CPP
      CP producing 55% and 46% reductions in smooth surface and fissure caries
      activity, respectively, being similar to that of 500 ppm F. The anticariogenic
      effects of CPP-CP and fluoride were additive, since animals receiving 0.5% CPP-CP
      plus 500 ppm F had significantly lower caries activity than those animals
      receiving either CPP-CP or fluoride alone. The tryptic digest of casein with the
      phosphopeptides selectively removed showed no anticariogenic activity. The
      synthetic octapeptide-calcium phosphate complex significantly reduced caries
      activity, confirming that this calcium-phosphate-stabilizing portion of the
      casein phospho-peptides is associated with anticariogenicity. The CPP-CP did not
      significantly affect the level of S. sobrinus in fissure plaque.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7629337
TI  - Arachidonic acid stimulates intracellular calcium mobilization and regulates
      protein synthesis, ATP levels, and mucin secretion in submandibular gland cells.
AB  - Earlier observations that arachidonic acid inhibited the synthesis of membrane
      inositol phospholipids in rat submandibular acinar cells prompted the present
      study on whether the fatty acid may also regulate other key physiological
      processes in the model. Arachidonate, at concentrations above 10 mumol/L,
      inhibited up to 97% protein synthesis in acinar cells. The acid also lowered
      cellular ATP levels to 25% of control values by a ouabain-insensitive mechanism.
      In endoplasmic reticulum-calcium studies in permeabilized cells, arachidonic acid
      stimulated the mobilization of up to 73% loaded ER-45Ca2+ to the cytosol, a much
      greater response than those caused by other calcium translocators, thapsigargin
      or inositol 1,4,5-trisphosphate. Additionally, arachidonate provoked the release
      of over 80% of total cell 45Ca2+ to the extracellular space in intact cells and
      stimulated mucin secretion in the submandibular model. The inhibitory effect of
      arachidonic acid on protein synthesis was duplicated by carbachol, thapsigargin,
      and BAPTA/AM, three agents that cause net efflux of ER-Ca2+ by different
      mechanisms. Furthermore, comparable with the arachidonate effect on ATP,
      carbachol and thapsigargin also significantly reduced cellular levels of the
      nucleotide. It is concluded that arachidonic acid acts as a regulator of central
      synthetic/secretory processes in mucous acinar cells of rat submandibular gland
      and suggested that at least some of its effects may be secondary to its calcium
      mobilizing action.

PMID- 7629338
TI  - Isolation, purification, and partial characterization of an autocrine periodontal
      ligament cell chemotactic factor.
AB  - Periodontal ligament (PDL) cells are believed to play a critically important role
      in the regeneration of the periodontium. We have suggested that polypeptide
      growth factors can enhance periodontal regeneration by stimulating PDL cell
      chemotaxis and mitogenesis. This manuscript describes the identification of a
      novel chemotactic factor isolated from human PDL cells which we named PDL-CTX.
      PDL-CTX induces the directed migration of human PDL cells in vitro and was found
      to be a more potent chemotactic agent than other known growth factors.
      Additionally, PDL-CTX has no chemotactic effect on gingival fibroblasts or
      gingival epithelial cells. Both tryptic digestion and boiling abolished PDL-CTX's
      biological activity. The designed purification method included Mono-S cation
      exchange, heparin-sepharose affinity, and microbore reverse-phase HPLC. The
      purified factor has a relative molecular weight of approximately 7000 daltons
      based on sodium dodecyl sulfate (SDS) gel analysis. The amino acid composition
      and partial amino acid sequence were determined from HPLC-purified material.
      These were determined to be unique. Further investigation of the biological
      functions of PDL-CTX on PDL cells and other ligament cells should help improve
      our understanding of ligament repair.

PMID- 7629339
TI  - A quantitative study on the myelinated fiber innervation of the periodontal
      ligament of cat canine teeth.
AB  - The periodontal ligament is richly innervated with mechanosensitive afferent
      nerve fibers, and the location of the mechanoreceptive terminals within the
      ligament is of functional significance. In this study, we have obtained
      quantitative information on mechanoreceptor distribution in the lower canine
      teeth of the cat. Using light microscopy, we quantified the number of myelinated
      axons in the periodontal ligament at 1 mm, 3 mm, and 5 mm from the tooth root
      apex. Grouped axons and axons which were isolated in the cemental half of the
      ligament (and therefore putative mechanoreceptors) were identified. The mean
      total number of axons was 1290 (n = 20) at 1 mm from the apex, 1290 at 3 mm, and
      814 at 5 mm. The distribution of axons around the tooth root circumference was
      found to be non-uniform. Near the root apex, the highest numbers of grouped axons
      were located distally and mesially, and in the middle region of the root, the
      highest numbers were found mesially. The highest numbers of isolated axons at the
      apical levels were located distally, and in the mid-root region, mesially. At all
      levels, the lingual region was the most sparsely innervated by both groups. There
      was a positive correlation between the number of grouped axons and the width of
      the ligament in the same region, but this correlation was much weaker for
      isolated axons, suggesting that their distribution does not result only from the
      volume of tissue. Variations in the number of axons and, to a lesser extent, the
      dimensions of the periodontal ligament were considerable.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7629340
TI  - Electromyographic heterogeneity in the human temporalis and masseter muscles
      during static biting, open/close excursions, and chewing.
AB  - The human temporalis and masseter muscles are not activated homogeneously during
      static bite force tasks. In this study, we studied the possible existence of
      regional differences in these muscles under dynamic conditions. Electromyographic
      (EMG) activity was recorded by means of bipolar fine-wire electrodes. Six
      electrodes were inserted into the temporalis muscle and three into the masseter
      muscle. Recordings were made during maximal effort intercuspal and incisal static
      clenches, open/close excursions from both the intercuspal and incisal positions,
      and unilateral gum and licorice chewing on right and left sides. The EMG peak
      amplitudes and the peak occurrences were compared. During the static clenches and
      the open/close excursions, no differences could be demonstrated between the
      regions of the temporalis muscle. However, during the chewing tasks, the anterior
      and posterior regions behaved differently. Throughout almost all tasks, both
      superficial and deep parts could be distinguished in the masseter muscle. A
      further division of the deep masseter was task-dependent. In both the temporalis
      and masseter muscles, maximal activity (100%) was reached during intercuspal
      clenches. The average activity declined to 35% of the maximal activity in the
      temporalis muscle, to 47% in the deep, and to 86% in the superficial masseter
      during incisal clenches. During all chewing tasks, the EMG peak activity of the
      anterior temporalis and the superficial masseter muscles was higher in the
      working than in the balancing condition. The general finding was that different
      regions were preferentially activated, according to task. The detailed regional
      specialization previously observed during static bite force tasks could not be
      demonstrated in the present study.

PMID- 7629341
TI  - Characterization and identification of proteinases and proteinase inhibitors
      synthesized by temporomandibular joint disc cells.
AB  - The adult mammalian temporomandibular joint (TM) disc is a fibrocartilaginous
      tissue that undergoes normal developmental remodeling, requiring removal of the
      existing extracellular matrix and its replacement by new matrix macromolecules.
      This remodeling is probably mediated by matrix-degrading enzymes, but to date
      none has been demonstrated in association with the TMJ disc. We characterized,
      identified, and determined the regulation of proteinases and proteinase inhibitor
      (PIs) synthesized by TMJ disc cells in organ and cell cultures. TMJ discs were
      retrieved from 14-week-old male NZW rabbits and both tissue- and disc-derived
      cells were cultured in serum-free medium. The conditioned media were retrieved at
      12-hour intervals and assayed for proteinases and PIs in gelatin- and casein
      impregnated polyacrylamide gels. Three proteinases with gelatinolytic activities
      at 92 kDa, 72 kDa, and 42/57 kDa and one caseinolytic activity at 51/54 kDa were
      detected. All were inhibited by 1,10-1 phenanthroline, thus characterizing these
      enzymes as matrix metalloproteinases (MMPs), most likely 92-kDa gelatinase
      (proMMP-9), 72-kDa gelatinase (proMMP-2), procollagenase (proMMP-1), and
      prostromelysin (proMMP-3). The identity of the latter two MMPs was confirmed by
      Western blots. Two PIs and 30 kDa and 20 kDa, probably tissue inhibitors of
      metalloproteinase (TIMP) and TIMP-2, were observed on reverse zymograms. TPA, a
      protein kinase-C agonist, increased the expression of 92-kDa gelatinase and 30
      kDa PI by both explanted discs and isolated disc cells. The profile of MMPs
      constitutively expressed by disc cells is similar to that of synovial fibroblasts
      but different from that of chondrocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7629342
TI  - Salivary function and hypertension: a review of the literature and a case report.
AB  - Limited evidence suggests a relationship between the use of antihypertensive
      medications and reduced salivary function. This article provides a review of the
      literature concerning the relationship between hypertension, hypertensive therapy
      and salivary function. A case report is presented to illustrate changes in
      salivary function in response to different types of antihypertensive medications.

PMID- 7629343
TI  - A case report. Gingival swelling due to a fingernail-biting habit.
AB  - There are many causes of gingival swelling in children and adolescents. This case
      report of a 9-year-old boy identifies nail-biting habits as one of these causes.
      Nail biting can also cause other localized oral problems.

PMID- 7629344
TI  - A case report. Bilateral transmigration of impacted mandibular canines.
AB  - Case reports have described displacement and migration of teeth in the upper and
      lower dental arches, but migration of a tooth across the mandibular midline is
      rare. The authors describe an extremely rare case of bilateral transmigration of
      impacted permanent canines across the midline of the mandible.

PMID- 7629345
TI  - A case report. Forced eruption of an impacted lower canine in a 48-year-old man.
AB  - A 48-year-old man was treated orthodontically in an attempt to erupt his lower
      right impacted canine. He wore the fixed appliances for 23 months and the
      treatment was successful.

PMID- 7629346
TI  - A case report. Jaw claudication: a sign of giant cell arteritis.
AB  - Jaw claudication is an often unrecognized sign of giant cell arteritis. The
      significance of this symptom has been underemphasized in the dental literature.
      Dentists should consider jaw claudication when making the differential diagnosis
      of jaw pain, especially in the elderly patient. Early diagnosis and treatment of
      giant cell arteritis may help save a patient's vision.

PMID- 7629347
TI  - Treatment alternatives for patients with masticatory myofascial pain.
AB  - Alternative therapies are used by many people, and the dental literature has
      reported that some alternative therapies are comparable to splint therapy in the
      effective treatment of masticatory myofascial pain. The authors review the
      efficacy of alternative therapies and discuss their clinical implications. This
      review is intended to help dental practitioners to select alternative therapies
      they can use with or instead of splint therapy for treating patients who have a
      primary diagnosis of myofascial pain.

PMID- 7629348
TI  - Making better removable partial dentures.

PMID- 7629350
TI  - MSAs: back to the future.

PMID- 7629349
TI  - Malpractice premiums in 1992: results of a national survey of dentists.
AB  - According to a 1992 national survey, more than 95 percent of general dentists in
      the United States purchased malpractice insurance. The authors evaluated the
      survey findings to identify factors that had the greatest effect on dentists'
      insurance premium costs. Premiums were higher for dentists who had been the
      subject of previous complaints or claims, as well as for those who owned their
      practices. States with fewer lawyers had lower premiums. Finally, state limits on
      use of dental hygienists, number of offices and the extent of water fluoridation
      also affected premium levels.

PMID- 7629351
TI  - Oklahoma disaster.

PMID- 7629352
TI  - Dental practice parameters.

PMID- 7629353
TI  - Managed care.

PMID- 7629354
TI  - Parameters counterpoint.

PMID- 7629355
TI  - Bonding amalgams.

PMID- 7629357
TI  - Consumer confidence up in 1994.

PMID- 7629356
TI  - Dental bills.

PMID- 7629358
TI  - Good news from the CDC.

PMID- 7629359
TI  - Tooth loss higher among elderly blacks than elderly whites.

PMID- 7629360
TI  - Burning mouth syndrome: an update.
AB  - Though it has been the subject of much research, burning mouth syndrome--a
      chronic oral-facial pain condition that affects many U.S. adults--remains poorly
      understood. It has been associated with numerous oral and systemic conditions.
      Treatment options frequently include various medications. While patients with
      symptoms of BMS are more likely to seek care from physicians, dentists should be
      involved in the evaluation and management of these patients.

PMID- 7629361
TI  - Atypical facial pain: the consistency of ipsilateral. Maxillary area tenderness
      and elevated temperature.
AB  - A consistent zone of ipsilateral tenderness adjacent to the maxillary molar root
      apices often is present in patients with atypical facial pain. The author
      performed bilateral palpation and recorded the temperature of this area on 18
      consecutive patients with facial pain. He found tenderness and increased
      temperature on the involved side of the face in 15 and 17 patients, respectively.
      In two control groups of 10 patients without pain and 10 TMD patients, he
      observed no significant association between maxillary tenderness and increased
      temperature.

PMID- 7629363
TI  - Using computers to diagnose and plan treatment of approximal caries. Detected in
      radiographs.
AB  - Two of the authors developed a computer-based software system that is capable of
      diagnosing approximal caries and making decisions about restorative care. The
      system was compared with decisions made by a group of experienced clinicians. The
      results indicate that the clinician viewers overall correctly identified a
      similar number of surfaces as the software, but from viewer to viewer, there was
      more variability in the number of surfaces identified correctly than in those
      identified correctly by the software users. Software packages such as this have
      the potential to raise overall accuracy by increasing the consistency of
      treatment decisions over time.

PMID- 7629362
TI  - Assessing HIV-related attitudes and orientations of male and female general
      dentists.
AB  - This article examines differences between male and female general practitioners
      in private practice in New York City with regard to their attitudes and
      orientations toward treating HIV-infected patients. The survey asked about
      willingness to treat such patients and perceptions that might influence that
      willingness, particularly those related to safety and self-efficacy and risk of
      occupationally acquiring HIV. Possible explanations for gender-related
      differences are considered. Implications of these findings for the development of
      HIV-related continuing education programs are discussed.

PMID- 7629364
TI  - Analysis of refractive corrections in spectacles donated to VOSH.

PMID- 7629365
TI  - We owe it to our patients ... and to our profession.

PMID- 7629366
TI  - Quality of care in cataract surgery cases experiencing post-operative
      complications with co-managed care.
AB  - BACKGROUND: The quality of co-managed services and the ability of community
      optometrists to diagnose complications following cataract surgery were
      investigated in a previous study of 2,458 cases. Questions were raised about the
      quality of co-managed care in 50 of the cases; this study evaluates the care
      received by these patients. METHODS: Medical records for 44 cases (6 cases could
      not located) were reviewed to determine whether community optometrists diagnosed
      post-surgical complications and whether cases were effectively managed. All
      reviews were performed by two optometrists and an ophthalmologist. Six cases were
      excluded because of no complication or attribution to underlying disease.
      RESULTS: In 34 of the 38 remaining cases (89.5%), co-management was successful in
      diagnosing complications and in managing the patient to maximize vision function.
      99.8% (2,454 of 2,458) of co-managed cases contained evidence that the
      optometrists provided high quality post-operative care and were able to diagnose
      complications. Using physician evaluations as the standard, the sensitivity of
      detection of complications by optometrists was 95.9% and the specificity was
      99.5%. CONCLUSIONS: Co-managing optometrists provide quality care and can
      diagnose post-operative complications.

PMID- 7629367
TI  - A profile of the demographics, training and driving history of telescopic drivers
      in the state of Michigan.
AB  - BACKGROUND: Five-hundred twenty-eight licensed, telescopic drivers in the state
      of Michigan, were sent a questionnaire consisting of 50 questions to evaluate the
      demographics, formal training procedures experienced by these drivers, and their
      driving habits. METHODS: One-hundred forty-nine responses were tabulated to
      determine the characteristics of the telescopic driver in the state of Michigan.
      RESULTS: The findings show an increased necessity for dynamic assessment,
      training and follow-up of the telescopic wearer and for referral to a specific
      driving program to establish safe driving skills. CONCLUSION: As the field of low
      vision expands in its delivery of care, and with improvement in technology, the
      desire for telescopic driver's licenses will increase. The need for dynamic
      training procedures delivered by the multidisciplinary rehabilitative team
      becomes even more vital to ensure safe driving skills and to protect the
      privilege to drive. Extensive training, followup and communication must be an
      integral part of this process.

PMID- 7629368
TI  - Quality of life: a review.
AB  - BACKGROUND: Quality of life has become an important issue in evaluating clinical
      research outcomes, and in relationship to cost containment and managed care
      issues. METHODS: The literature on quality of life was reviewed to give the
      practicing optometrist an overview of the issue. RESULTS: Quality of life
      embraces a wide range of physical and psychological characteristics that describe
      a person's functional ability. There is no agreed upon definition of quality of
      life. This lack of agreement has led most researchers to adopt a multidimensional
      approach toward assessing quality of life since no single parameter has ever
      proven to be adequate. CONCLUSION: Quality of life measurement is an important
      issue in health care research and policy. In the future, awareness of quality of
      life issues will be of increasing importance for the optometrist.

PMID- 7629369
TI  - The fragile X female: a case report of the visual, visual perceptual, and ocular
      health findings.
AB  - BACKGROUND: Fragile X syndrome is one of the most frequently encountered
      etiologies of X-linked mental retardation. Even though it is second only to Down
      syndrome in prevalence among children with chromosomal abnormalities, few studies
      have investigated the visual, visual perceptual and ocular health anomalies
      associated with this syndrome. No studies have been published that report on
      these areas for females with fragile X. This case report describes a 10-year-old
      white female with fragile X syndrome who exhibited numerous oculo-visual and
      perceptual abnormalities. METHODS: A 10-year, 7-month-old white female diagnosed
      as having fragile X syndrome was examined in the Illinois Eye Institute/Illinois
      College of Optometry Department of Pediatrics and Binocular Vision using
      diagnostic techniques appropriate for special populations. These techniques
      included a battery of tests that determine binocular vision function, ocular
      health status and visual perceptual abilities. RESULTS: Oculo-visual
      abnormalities noted include a non-active chorioretinal lesion, refractive
      amblyopia, anisometropia, accommodative insufficiency, and convergence excess, as
      well as mild to severe dysfunctions in visual motor integration, ocular
      motilities, laterality/directionality, visual figure ground, visual closure,
      visual form constancy, visual memory and visual sequential memory. CONCLUSION:
      Although thousands of articles, monographs, and textbooks have been written
      describing the numerous anomalies associated with the fragile X syndrome, little
      has been published in the area of oculo-visual and visual perceptual dysfunctions
      associated with this frequently encountered genetic abnormality. This paper is
      the first to demonstrate the presence of ocular health anomalies and learning
      related vision problems that could adversely affect the individual's academic
      performance and rehabilitative program. Additional research is needed to
      ascertain the prevalence of these disorders within the fragile X community.

PMID- 7629370
TI  - Lined multifocal wearers prefer progressive addition lenses.
AB  - BACKGROUND: Despite reported successes with progressive addition lenses, lined
      multifocals remain the lens of choice for previous lined multifocal wearers.
      METHODS: To explore the feasibility of switching lined multifocal wearers to
      PALs, in a prospective clinical trial we interviewed 265 lined multifocal
      wearers, prescribed a new PAL (Varilux Comfort) and then interviewed them again
      to compare the lens types and patient preferences. RESULTS: PALs ranked
      significantly higher than lined multifocals for all questions and were preferred
      by 92 percent of the patients. CONCLUSIONS: PALs should be the lens of choice for
      previous bifocal wearers.

PMID- 7629371
TI  - Valsalva maneuver induced vitreous hemorrhage.
AB  - BACKGROUND: A 43 year old male who performed a severe and sustained Valsalva
      maneuver developed a vitreous hemorrhage that was suspected as originating from
      an optic nerve vessel. Valsalva hemorrhagic retinopathy is not a common ocular
      finding and a breakthrough into the vitreous is even more uncommon. The vitreous
      hemorrhage cleared with recovery of previous acuity levels and a residua of small
      areas of fibrosis in the inferior vitreous. A discussion of the physiology of the
      Valsalva maneuver and of possible ocular and nonocular complications is
      presented. There is also a discussion of how this maneuver is used in the
      diagnosis of orbital diseases. CONCLUSION: In this case a vitreous hemorrhage was
      induced by a marked and sustained Valsalva maneuver which resolved without
      significant sequelae. The Valsalva maneuver is capable of causing many ocular
      complications; it is important to advise patients about the potential side
      effects of this maneuver.

PMID- 7629372
TI  - Binocular vision anomalies: an emerging cause of malpractice claims.
AB  - BACKGROUND: Tumors that affect the visual system are a significant cause of
      liability claims involving eyecare practitioners. Individuals with brain tumors
      or intraocular tumors may seek examination for associated binocular vision
      disorders such as strabismus and reduced acuity. A disporportionate number of
      these individuals are children. METHODS: A review of malpractice claims was
      performed to identify representative clinical presentations in which binocular
      vision disorders were the cause for examination. RESULTS: Strabismus and
      amblyopia in children, if not promptly diagnosed and properly treated, can be the
      basis for a malpractice claim. Binocular vision disorders may also result from
      brain or intraocular tumors affecting children, and failure to timely detect the
      presence of these underlying diseases can also become the basis for a malpractice
      claim. CONCLUSIONS: Eyecare practitioners should examine carefully children with
      binocular vision disorders to rule out the possibility of an associated brain or
      intraocular tumor. Key findings include decreased visual acuity, acute
      strabismus, and indications of neurological disease such as optic atrophy,
      papilledema, visual field loss, and problems with gait and coordination.

PMID- 7629373
TI  - Harold Lloyd, the man who popularized eyeglasses in America.
AB  - BACKGROUND: Harold Lloyd was a cinema comedian who set records for popularity at
      the box office while establishing a unique screen persona. His character's
      distinquishing feature was a pair of spectacles made of tortise shell. Lloyd's
      screen character was so popular that, during the 1920s, the wear of spectacles
      became acceptable and faddish and contributed significantly to the popularization
      of eyewear.

PMID- 7629374
TI  - The effect of sodium valproate on luteinizing hormone secretion in women with
      polycystic ovary disease.
AB  - The aim of this study was to examine whether modulation of the GABA-ergic system
      (with sodium valproate) affects gonadotropin secretory frequency and amplitude in
      women with polycystic ovarian syndrome (PCOS). Six women aged 25 +/- 2 years with
      diagnosed PCOS and six healthy women aged 26 +/- 2 years at day 7-11 of menstrual
      cycle were included in the study. Sodium valproate 1200 mg p.o./day (600 mg
      t.i.d.) was administered for five days in both groups. Efficacy of treatment was
      assessed in women with PCOS by measuring six hour LH pulsatility (every .10 min),
      and by GnRH tests before and after treatment. Basal serum steroids were assessed
      as well. Hormones were determined by radioimmunoassay and pulse detection was
      carried out by the program PULSAR. The administration of valproate did not change
      basal serum LH concentration (9.1 +/- 0.6 vs 9.0 +/- 0.8 IU/L p > 0.05) nor LH
      pulse frequency (7.3 +/- 0.5 vs 6.3 +/- 0.5 p > 0.05) or the LH pulse amplitude
      (3.0 +/- 0.5 vs 3.5 +/- 0.4 p > 0.05). LH response to GnRH (mean peak 43.6 +/-
      5.2 vs 44.1 +/- 6.0 IU/L p > 0.05) did not change either. Valproate did not
      affect the LH secretory activity in women with PCOS. There was no change in FSH,
      and prolactin secretion. In five patients with PCOS valproate caused further
      increase in serum testosterone level but this did not reach significance in the
      group as a whole (5.6 +/- 1.0 vs 9.1 +/- 2.0 nmol/L p > 0.05).

PMID- 7629375
TI  - Thyroid Cancer: Basic Science and Clinical Problems. Proceedings of an
      international workshop. Taormina, December 2-4, 1993.

PMID- 7629376
TI  - Molecular events in the differentiation of the thyroid gland.

PMID- 7629377
TI  - Positive control of proliferation by the cyclic AMP cascade: an oncogenic
      mechanism of hyper-functional adenoma.

PMID- 7629379
TI  - RET/PTC activation in human thyroid carcinomas.

PMID- 7629378
TI  - Role of ras and gsp oncogenes in human epithelial thyroid tumorigenesis.

PMID- 7629380
TI  - Rearrangements of TRK proto-oncogene in papillary thyroid carcinomas.

PMID- 7629381
TI  - Overexpression of the c-MET/HGF receptor in human thyroid carcinomas derived from
      the follicular epithelium.

PMID- 7629383
TI  - Thyroid cancer following Chernobyl.

PMID- 7629382
TI  - Tumor suppressor genes in human thyroid neoplasms: p53 mutations are associated
      undifferentiated thyroid cancers.

PMID- 7629384
TI  - Cancer in iodine-131 exposed patients.

PMID- 7629386
TI  - Morphological aspects of thyroid cancer and tumour prognosis.

PMID- 7629385
TI  - Outcome of pregnancy in women with thyroid carcinoma.

PMID- 7629387
TI  - The management of thyroid nodules.

PMID- 7629388
TI  - Prognostic factors in the management of thyroid cancer.

PMID- 7629389
TI  - Differentiated thyroid carcinoma in childhood.

PMID- 7629390
TI  - Post-surgical follow-up of differentiated thyroid cancer.

PMID- 7629391
TI  - Recurrent thyroid cancer.

PMID- 7629392
TI  - Treatment of distant metastases of differentiated thyroid carcinoma.

PMID- 7629393
TI  - Thyroid function and autoimmunity in pernicious anemia before and during
      cyanocobalamin treatment.
AB  - Out of 35 consecutive patients with decreased plasma-cobalamin 22 had newly
      diagnosed overt pernicious anemia (PA) six of which had a known history of
      thyroid disease. At referral, 5 of these 6 were thyroid peroxidase antibody
      (TPOAb)-positive and 2 were thyroglobulin antibody (TgAb)-positive, while none
      were thyroid stimulating antibody (TSAb)-positive (an overall autoantibody
      appearance of 83.3%). Fifty percent of the 22 patients had TPOAb and 13.6% had
      TgAb compared to 18.2% and 4.5%, respectively in sex and age matched healthy
      controls. Six PA-patients without a history of thyroid disease had thyroid
      autoantibodies and another patient seroconverted within the first year during
      treatment with cyanocobalamin. Measurements of serum concentrations of thyroid
      hormones and thyroid stimulating hormone were performed during the first year of
      treatment with cyanocobalamin. Two cases of subclinical myxoedema were found
      among PA-patients and another case was found among patients with latent PA. The
      female:male ratio of thyroid disease among PA-patients and among thyroid
      autoantibody-positive PA-patients was interestingly found to be 1:1. Treatment
      with cyanocobalamin did not have any systematic effect on thyroid function.
      Routine screening for thyroid function and thyroid autoantibodies in patients
      with latent or overt PA is recommended.

PMID- 7629394
TI  - Usefulness of early morning urine estrone-3-glucuronide assay in the monitoring
      ovarian secretory function in precocious puberty.
AB  - To evaluate the usefulness of the urinary estrone-3-glucuronide (EI-3-G) in the
      monitoring of the ovarian function in girls, we studied 11 girls with idiopathic
      central precocious puberty (ICPP) treated with LHRH analogs (LHRHa) for 2-5
      years. Plasma LH, FSH, 17-beta-Estradiol (E2) levels, early morning urine (EMU)
      E1-3-G concentrations, were assessed before and 3, 6, 12 months after the onset
      of treatment. As expected, mean basal plasma LH, FSH and E2 concentrations, as
      well as mean basal EMU E1-3-G levels were significantly (p < 0.01) higher in
      patients studied than in normal, age matched, prepubertal controls. Three out of
      the 11 sexually advanced girls showed undetectable (< 15 pg/ml) basal plasma E2
      values. On the contrary, in each patient studied, individual basal E1-3-G levels
      were higher than in normal age-matched prepubertal girls. LHRHa treatment
      significantly suppressed both basal and peak stimulated plasma gonadotropins,
      plasma E2 and EMU E1-3-G. However, while serum E2 levels were below the assay
      detection limit, not allowing to assess the degree of gonadal suppression, E1-3-G
      urinary concentrations were detectable in each subject treated, in the range of
      the normal prepubertal values. EMU E1-3-G determination seems to be a very
      sensitive and reliable approach to the monitoring of the effectiveness of LHRHa
      treatment in sexually advanced girls, allowing to detect very low estrogen
      concentrations and to achieve the desired ovarian suppression.

PMID- 7629395
TI  - Bibliography of the current world literature in hypertension.

PMID- 7629396
TI  - The 'high-risk' and 'mass' strategies for control of blood pressure.

PMID- 7629397
TI  - Prevention of high blood pressure and its complications: strategic issues in a
      local context.

PMID- 7629398
TI  - Neuropeptide Y: a possible role in hypertension?
AB  - PURPOSE: To evaluate whether neuropeptide Y (NPY) is likely to be relevant as a
      regulator of cardiovascular function in general and of blood pressure control in
      arterial hypertension in particular, based on a literature survey. RESULTS OF
      DATA ANALYSIS: NPY is a putative cotransmitter of many central and peripheral
      sympathetic neurons. It and its receptors are present in brain areas and
      peripheral tissues involved in cardiovascular regulation, and administration of
      exogenous NPY to these sites can elicit functional cardiovascular responses by
      acting on specific pre- and postsynaptic receptors. Moreover, NPY may act as a
      growth factor for the development of vascular and cardiac hypertrophy. The
      release of NPY and postsynaptic vasoconstriction responses to NPY may be enhanced
      in hypertension, whereas presynaptic inhibitory responses may be attenuated. Some
      of these alterations may precede the development of blood pressure elevations in
      the spontaneously hypertensive rat model of genetic hypertension. CONCLUSIONS:
      NPY might be an important physiological and pathophysiological modulator of
      cardiovascular function, but further studies using specific high-affinity
      antagonists are required.

PMID- 7629399
TI  - Heart mass and blood pressure have separate genetic determinants in the New
      Zealand genetically hypertensive (GH) rat.
AB  - OBJECTIVE: To determine associations between cardiovascular parameters and
      genotype in 205 F2 rats of both sexes and lineages from reciprocal crosses made
      between rats of the New Zealand genetically hypertensive (GH) and Brown Norway
      (BN) rat strains. METHODS: Systolic tail blood pressure, mean arterial blood
      pressure, pulse rate, heart mass, body mass and relative heart mass were
      determined for each rat in the age range 17-19 weeks, and DNA polymorphisms were
      examined for the guanylyl cyclase A (GCA), angiotensin converting enzyme (ACE)
      and renin (REN) genes. RESULTS: The phenotypic data indicated the presence of
      genes on the X and Y chromosomes that affected blood pressure. The GH GCA allele,
      in males only, and the GH ACE allele, in females only, both cosegregated with
      increased blood pressure. The ACE effect was confined to rats of one lineage
      only, namely those with GH grandfathers. A cosegregation of the GH REN allele
      with decreased blood pressure was also detected in females with BN grandfathers.
      In contrast, the GH REN allele cosegregated with a smaller heart in males only,
      whereas the GH ACE allele cosegregated with a larger heart both in males and in
      females. In males this was the consequence of a decrease in body mass with no
      change in absolute heart mass, whereas in females there were changes in both of
      these parameters. CONCLUSIONS: The results show that cardiac hypertrophy and
      blood pressure have independent genetic determinants in the GH rat, and indicate
      the importance of sex in determining the phenotypic expression of genes
      underlying cardiovascular pathology.

PMID- 7629400
TI  - Effects of urban noise pollution on blood pressure and heart rate in preschool
      children.
AB  - OBJECTIVE: To investigate the association between long-term exposure to high
      level urban traffic noise and blood pressure in preschool children. DESIGN:
      Normotensive children (n = 1542), aged 3-7 years and attending kindergartens, had
      their blood pressures and heart rate measured. Mean values of these circulatory
      variables were related to 24-h equivalent traffic noise emission levels measured
      near their kindergartens and homes. METHODS: Supine systolic (SBP) and diastolic
      blood pressure (DBP) were measured by a Doppler ultrasonic device, heart rate by
      palpitation. Weighted average sound pressure levels were measured for 24 h a
      working day at 275 places in the city. An anthropometric investigation was
      performed. Demographic, socio-economic and health status questionnaires were
      completed by the parents of the children. RESULTS: Children attending
      kindergartens situated in areas with traffic noise > 60 dB(A) had higher mean SBP
      and DBP and lower mean heart rate than children in quiet areas. Noise at
      kindergartens had a greater impact than at homes. CONCLUSIONS: Medium- and high
      level urban traffic noise [> 60 dB(A)] near kindergartens is associated in
      preschool children with higher mean SBP and DBP, and with a higher incidence of
      children with blood pressure values above the respective 95th centiles. The
      increase in DBP could be ascribed to the rise in peripheral vascular tone and the
      decrease in heart rate, possibly owing to activation of a baroreceptor mechanism.

PMID- 7629401
TI  - Measures of blood pressure and myocardial infarction in treated hypertensive
      patients.
AB  - OBJECTIVE: To identify entry characteristics associated with subsequent
      myocardial infarction in treated hypertensive patients. DESIGN: Nested case
      control study and cohort study. SETTING AND PATIENTS: The 5730 participants (mean
      age 53 years; 61% male and 45% Caucasian) were selected from a worksite-based,
      union-sponsored, systematic hypertension control program from 1973 to 1992.
      METHODS: In the case-control study myocardial infarction cases were matched by
      age, sex, year of entry to the program, years of follow-up and previous treatment
      status (treated or untreated) with non-event subjects. Baseline clinical and
      biochemical characteristics were analyzed with regard to the outcome of
      myocardial infarction, using univariate and multivariate analyses, respectively,
      in case-control and cohort studies. RESULTS: During 5.43 years of follow-up the
      incidence of myocardial infarction was 6.75/1000 person-years. Univariate
      analysis indicated that myocardial infarction cases had higher cholesterol level
      and were more likely to have a previous history of diabetes than controls. The
      initial systolic blood pressure and pulse pressure of cases were significantly
      higher than in controls. Logistic regression models indicated that initial pulse
      pressure, either as a continuous or as a categorical variable, was the only
      measure of blood pressure independently associated with myocardial infarction
      after adjustment for other risk factors. Analysis of the experience of the total
      5730 as well as 2445 previously untreated patients with a cohort study generated
      identical results. CONCLUSION: A large pulse pressure difference appears to be
      the most powerful measure available of initial blood pressure to identify, in
      advance, those hypertensive patients at greatest risk for a subsequent myocardial
      infarction.

PMID- 7629402
TI  - Is the relationship between supine blood pressure and postural changes in blood
      pressure artefactual? Results from the Kuopio Ischemic Heart Disease Risk Factor
      Study.
AB  - OBJECTIVE: To investigate whether there is an association between initial supine
      blood pressure and postural changes in blood pressure (standing minus supine
      blood pressure). METHODS: Using data from the Kuopio (Finland) Ischemic Heart
      Disease Risk Factor Study (KIHD), we simulated the problem and found the
      suggested solution based on the work of Blomqvist. We then applied the Blomqvist
      correction to the KIHD data with real measurement errors. RESULTS: The observed
      regression slope was substantially reduced, indicating that there is no
      relationship between the initial blood pressure and the postural change in blood
      pressure. CONCLUSION: Only the broad application of the method of Blomqvist to
      other data sets will determine the generalizability of the present finding that
      initial blood pressure is unrelated to the postural change in blood pressure.

PMID- 7629403
TI  - Plasma insulin and blood pressure in normotensive Japanese men with normal
      glucose tolerance.
AB  - OBJECTIVE: To determine whether blood pressure within the normal range is
      associated with plasma insulin concentration in a Japanese population with normal
      glucose tolerance. METHODS: We studied 491 normotensive Japanese men with normal
      glucose tolerance, who had never been treated with antihypertensive medications.
      Plasma glucose and insulin response during a 75-g oral glucose-tolerance test,
      blood pressure, body mass index, serum lipids, alcohol consumption and smoking
      status were obtained. The subjects were divided into quartiles according to mean
      blood pressure level (< 79, 79-84, 85-91 and > or = 92 mmHg). To eliminate
      possible confounding factors, analysis of covariance was also performed. RESULTS:
      In univariate analyses the plasma insulin response after an oral glucose load,
      especially after 60 min, was significantly related to blood pressure level.
      Plasma glucose was related to blood pressure level only at fasting. When adjusted
      for age, body mass index, plasma glucose response and alcohol consumption, plasma
      insulin concentrations after 30 and 60 min in the highest quartile were
      significantly higher than those in the lowest quartile. CONCLUSIONS: Blood
      pressure was significantly and independently related to plasma insulin level
      after an oral glucose load in normotensive Japanese men with normal glucose
      tolerance. The results suggest that the relationship between blood pressure and
      insulin resistance already exists in a prehypertensive state even in a lean Asian
      population.

PMID- 7629404
TI  - Left ventricular hypertrophy in hypertension is associated with the insulin
      resistance metabolic syndrome.
AB  - OBJECTIVE: To investigate whether left ventricular hypertrophy is associated with
      the insulin resistance syndrome. METHODS: Fifty patients with untreated
      hypertension were evaluated by recording office blood pressure during regular
      antihypertensive treatment and 24-h ambulatory blood pressure and office blood
      pressure after 4-6 weeks on placebo, echocardiography with M-mode measurements of
      left ventricular wall thickness and pulsed-wave Doppler measurements of mitral
      flow in diastole and the hyperinsulinaemic euglycaemic clamp, for determination
      of insulin sensitivity. RESULTS: The left ventricular wall thickness was found to
      be significantly related to blood pressure [r = 0.44, P < 0.004 for 24-h
      ambulatory systolic blood pressure (SBP)], fasting insulin level (r = 0.32, P <
      0.03) and haematocrit level (r = 0.37, P < 0.009) and inversely related to
      insulin sensitivity (r = -0.59, P < 0.0001). Multiple regression analysis with
      these relationships together with confounding factors age, sex, body mass index
      and waist: hip ratio as independent variables showed insulin sensitivity to be
      the only significant variable, explaining 43% of the variation in left
      ventricular wall thickness, whereas 24-h ambulatory SBP explained a further 7%.
      Left ventricular diastolic filling, as evaluated by the mitral Doppler early:
      atrial ratio, was significantly correlated with insulin sensitivity (r = 0.42, P
      < 0.003) and inversely related to blood pressure (r = -0.41, P < 0.02 for 24-h
      ambulatory SBP), left ventricular wall thickness (r = -0.34, P < 0.02) and serum
      fibrinogen level (r = -0.63, P < 0.0001). However, multiple regression analysis
      showed that insulin sensitivity was more closely related to diastolic filling
      than to blood pressure or left ventricular wall thickness. CONCLUSION: The
      present study showed left ventricular wall thickness to be closely associated
      with insulin resistance. Because diastolic dysfunction of the left ventricle was
      also related to a decreased insulin sensitivity, these findings suggest that left
      ventricular hypertrophy and diastolic dysfunction are associated with the insulin
      resistance metabolic syndrome.

PMID- 7629405
TI  - Sympathetic nerve activity in conscious renal hypertensive rats treated with an
      angiotensin converting enzyme inhibitor or an angiotensin II antagonist.
AB  - OBJECTIVE: To assess in conscious two-kidney, one clip renal hypertensive rats
      whether angiotensin converting enzyme (ACE) inhibition with lisinopril,
      angiotensin II receptor blockade with losartan or vasodilation with sodium
      nitroprusside have similar effects on intra-arterial mean blood pressure, heart
      rate and splanchnic nerve activity. RESULTS: A bolus dose of lisinopril or
      losartan (both 10 mg/kg, intravenously) induced within 2 h an equal reduction in
      mean blood pressure, whereas sodium nitroprusside infused during the same period
      (at 10 micrograms/min) lowered mean blood pressure, but less strongly. The heart
      rate was accelerated significantly more during sodium nitroprusside infusion than
      during lisinopril or losartan treatment. Splanchnic nerve activity increased
      significantly only in those rats given sodium nitroprusside. No change in the
      parameters studied was observed in vehicle-treated rats. The doses of lisinopril
      and losartan were repeated after 12 and 24 h. Before administration of the last
      dose, the mean blood pressure was still low. Administration of lisinopril or
      losartan again 24 h after the initial dose had no further effect on the mean
      blood pressure, heart rate or splanchnic nerve activity. CONCLUSION: These
      results obtained in rats with a renin-dependent form of hypertension show that
      blockade of the renin-angiotensin system for 24 h produces an equivalent blood
      pressure reduction irrespective of whether it is due to ACE inhibition or
      angiotensin II antagonism. The results also indicate that there is less reflex
      activation of sympathetic nerve activity when blood pressure is lowered with a
      blocker of the renin-angiotensin system rather than with a direct vasodilator
      such as sodium nitroprusside.

PMID- 7629406
TI  - Influence of naloxone on muscle sympathetic nerve activity, systemic and calf
      haemodynamics and ambulatory blood pressure after exercise in mild essential
      hypertension.
AB  - OBJECTIVE: To determine the effects of prior exercise and naloxone on
      haemodynamics, muscle sympathetic nerve activity, pituitary hormones and
      ambulatory blood pressure. METHODS: We studied 14 mild hypertensive and 14
      normotensive subjects on two days. After baseline measurements, subjects were
      randomly allocated to vehicle or naloxone (0.4 mg/kg) 30 min before 45 min
      treadmill exercise. RESULTS: In both groups blood pressure, stroke volume, and
      calf and total peripheral resistances were lower 1 h after exercise, whereas
      sympathetic activity was unchanged. In normotensive subjects naloxone abolished
      this calf vasodilation without altering muscle sympathetic nerve activity, and
      attenuated these haemodynamic aftereffects of exercise, implying a peripheral
      opioidergic mechanism. Naloxone had no haemodynamic effect in hypertensive
      subjects. In normotensives there was an inverse relationship between changes in
      blood pressure and sympathetic activity after vehicle and exercise. This was
      transformed by naloxone into a positive relationship (r = 0.69, P < 0.02) similar
      to that observed in hypertensives after vehicle and exercise. Naloxone did not
      alter the latter positive relationship. Naloxone altered exercise-induced changes
      in prolactin and luteinizing hormone, but only in normotensive males. In both
      groups ambulatory blood pressures and heart rates over 2 h after subjects left
      the laboratory were higher than the values recorded at baseline or 1 h after
      exercise, and were unaffected by naloxone. CONCLUSIONS: The depressor effect of
      exercise is due to peripheral vasodilation, occurs in the absence of sympathetic
      withdrawal and is short-lived. Endogenous opioids, activated by running,
      participate in the haemodynamic, sympathoneural and pituitary hormone
      aftereffects of exercise in normotensive subjects, whereas in hypertensives these
      aftereffects of exercise are achieved through non-opioidergic mechanisms. These
      observations are consistent with the concept that activation of endogenous opioid
      systems by exercise is impaired in mild hypertension.

PMID- 7629407
TI  - Urinary albumin excretion is associated with the intima-media thickness of the
      carotid artery in hypertensive males with non-insulin-dependent diabetes
      mellitus.
AB  - OBJECTIVE: To examine the relationship between urinary albumin excretion and
      ultrasonographically assessed morphology of the common carotid artery in
      hypertensive men with and without non-insulin-dependent diabetes mellitus.
      DESIGN: Cross-sectional study. SETTING: An outpatient clinic in a city hospital.
      PATIENTS: Hypertensive male patients (n = 25) with non-insulin-dependent diabetes
      mellitus and non-diabetic hypertensive male patients (n = 94) aged 50-72 years,
      randomly selected from a larger study group. MAIN OUTCOME MEASURES: Overnight
      urinary albumin excretion and B-mode ultrasound examinations of the carotid
      artery. RESULTS: Among the diabetic patients the logarithm of the overnight
      urinary albumin excretion was independently and significantly associated with the
      common carotid artery intima-media thickness, which was also true after
      adjustment for concomitant cardiovascular disease. In the non-diabetic group
      there was no association between intima-media thickness and urinary albumin
      excretion. No relationship between the occurrence of plaque and urinary albumin
      excretion was observed in any of the study groups. The results were reproducible
      at a re-examination after 3 years using the same methods. CONCLUSION: Among the
      hypertensive men with non-insulin-dependent diabetes mellitus, an independent and
      significant relationship, reproducible after 3 years, was found between urinary
      albumin excretion and the intima-media thickness of the common carotid artery. No
      such relationship was found in the group of non-diabetic hypertensive males.

PMID- 7629408
TI  - Perindopril treatment prolonged the lifespan of spontaneously hypertensive rats.
AB  - OBJECTIVE: The effects of perindopril treatment on hypertension development and
      the lifespan of adult spontaneously hypertensive rats (SHR) were studied. DESIGN:
      Adult male SHR (aged 15 weeks) were given once a day treatment with 4 mg/kg
      perindopril by gavage for 12 weeks. Littermates given distilled water were used
      as controls. The blood pressure and lifespan of these rats were studied. METHODS:
      The systolic blood pressure (SBP), heart rate and body weight of these rats were
      measured at regular intervals until they died from natural causes. At necropsy
      macroscopic and microscopic examinations were made of various organs to determine
      the cause of death. Serum levels of creatinine, urea and protein were also
      measured. RESULTS: Perindopril treatment resulted in the normalization of SBP
      after 2 weeks of treatment. Withdrawal of the treatment after 12 weeks of
      treatment caused an elevation of SBP, but the blood pressure of the treated SHR
      had remained in the normotensive range (< or = 150 mmHg). The heart rate and body
      weight of the SHR were not affected by the treatment. The average lifespan of the
      SHR was increased by 12 weeks compared with the control rats. The heart weight,
      brain lesions and arterial lesions were reduced by the treatment. CONCLUSION: A
      12-week treatment of adult SHR with perindopril was effective in causing a
      permanent prevention of hypertension, amelioration of some of the tissue damage
      associated with hypertension and an increase in the lifespan of these rats.

PMID- 7629409
TI  - Assessment of pediatric pain: time for an agreement.

PMID- 7629410
TI  - Low-dose megestrol acetate for appetite stimulation in advanced cancer.

PMID- 7629411
TI  - Neuropathic pain caused by therapeutic ethanol embolization of a cutaneous
      hemangioma.

PMID- 7629412
TI  - Severe undertreatment of cancer pain: a 3-year survey of the German situation.
AB  - The aim of this survey was to determine the prescribing patterns of German
      physicians in the treatment of cancer pain. The computerized patient records of
      330 practices, which treated a total number of 1,104,435 patients over a 3-year
      period, were analyzed. "Strong" opioids, widely accepted in the management of
      severe cancer pain, were prescribed to just 322 of 16,630 cancer patients (1.9%).
      Only 99 (0.6%) patients received more than three prescriptions during more than 3
      weeks of treatment. Additionally, many prescriptions mandated inadequate time
      intervals for the dosing, and 12% of the prescriptions were given "as required."
      From these data, it can be concluded that the majority of cancer patients in
      Germany are not treated for pain at all, and that those patients who receive
      treatment are treated inadequately. Germany is still a developing country in
      terms of pain therapy. This situation is symptomatic of many countries and
      reflects the continuing prejudice against opioids.

PMID- 7629413
TI  - Dehydration and the dying patient.
AB  - This study investigated the relationship between symptoms and dehydration in 82
      subjects with malignant disease. Assessment of respiratory tract secretions,
      thirst, and dry mouth were made during the dying phase, and serum biochemistry
      was analyzed. Follow-up data were also collected when the patient died. The
      median time from entry into the study until death was 2 days. All subjects died
      without artificial fluid therapy. Analysis showed that over 50% of subjects had a
      serum osmolality of less than 295 mOsm/kg. Contrary to previous anecdotal
      evidence, no statistically significant relationship was demonstrated between the
      level of hydration and respiratory tract secretions. Twenty-eight percent of
      subjects were able to respond to questions; 87% of these had a dry mouth and 83%
      felt thirsty. No statistically significant association was found between level of
      hydration and these symptoms. Artificial hydration to alleviate these symptoms in
      the dying patient may, therefore, be futile. Further work needs to be carried out
      regarding the cause and treatment of these symptoms in the dying patient.

PMID- 7629414
TI  - Buffered lidocaine for skin infiltration prior to hemodialysis.
AB  - This study compared the effects of buffered versus unbuffered lidocaine when used
      as local anesthetic in preparation for cannulation of the arterial and venous
      sites of children requiring hemodialysis. The subjects for this study were seven
      children, ages 6-18 years, observed during 101 dialysis treatments. For each
      subject undergoing hemodialysis on a given day, one syringe containing 1%
      lidocaine (L) and one containing buffered lidocaine (BL) were prepared. The BL
      solution was prepared by adding 2 mL of 8.4% sodium bicarbonate to 20 mL of 1%
      lidocaine just prior to use. The choice of local anesthetic used for cannulation
      of the arterial or venous site was randomly assigned to be either L or BL.
      Nurses, raters, and subjects were blind to contents of the syringe. The
      procedures for piercing the skin, pausing, and infiltrating were standardized, as
      was the volume administered. Speed of injection was not controlled. Comparisons
      of self-reported pain and behavioral observations for L versus BL revealed no
      significant differences for pain of infiltration or pain of cannulation.
      Technique variables such as the speed of injection, which tended to be very slow
      for these children, appear to significantly influence infiltration pain and the
      relative merits of buffering.

PMID- 7629415
TI  - Staff nurses' perceptions of barriers to effective pain management.
AB  - The purpose of this study was to investigate staff nurses' perceptions of
      barriers to pain management including lack of educational preparation; inadequacy
      of clinical practice skills; and certain legal/political, financial, and ethical
      problems. Staff nurses rated the adequacy of their knowledge and skills in each
      of these areas as well as how important they believed each area was on a four
      point Likert scale (1 = very inadequate or very unimportant to 4 = very adequate
      or very important). Nurses were also asked to list the most important pain
      management problems in their institutions. A random sample of 24 hospitals
      stratified on the basis of size was drawn from four states in the United States.
      Of 125 nurses contacted, 108 (86%) responded to the questionnaire. Nurses rated
      their educational preparation (mean, 2.6; SD, 0.05) and knowledge of
      legal/political issues (mean, 2.3; SD, 0.05) midway between inadequate and
      adequate. Practice was rated as adequate (mean 3.1; SD, 0.36), and financial
      issues were rated as inadequate (mean, 1.9; SD, 0.06). Knowledge of ethical
      issues was adequate (mean, 3.1; SD, 0.03). Implications of these ratings based on
      the literature in pain management are discussed.

PMID- 7629416
TI  - Managing cancer pain: content and scope of an educational program for nurses who
      work in predominantly rural areas.
AB  - A great deal of effort is being expended at national, state and local levels to
      improve cancer pain management in the United States. The fact that cancer
      patients continue to experience "unrelieved pain" is of concern to professional
      caregivers and families, as well as to the patients themselves. This article
      describes the content and scope of an educational program for nurses who work in
      predominantly rural areas. Content of the program and the evaluation process are
      described in detail in order to provide other caregivers with a model that could
      be implemented in similar settings.

PMID- 7629417
TI  - Management of symptomatic malignant ascites with diuretics: two case reports and
      a review of the literature.
AB  - Malignant ascites is a common complication of advanced cancer. It is associated
      with distressing symptoms and poor prognosis. Treatment may be aimed at the
      underlying cancer but is rarely successful. Therapeutic success for the available
      symptomatic treatment options for ascites is often limited. Control of
      symptomatic malignant ascites is possible with the use of diuretics in selected
      patients, is well tolerated, and should be tried first.

PMID- 7629418
TI  - Oral capsaicin provides temporary relief for oral mucositis pain secondary to
      chemotherapy/radiation therapy.
AB  - Pain from oral mucositis afflicts from 40% to 70% of patients receiving
      chemotherapy or radiation therapy. Current methods of clinical pain management
      (for example, topical anesthetics, systemic analgesics) have limited success. In
      a pilot study, we examined the ability of oral capsaicin to provide temporary
      relief of oral mucositis pain. Capsaicin, the active ingredient in chili peppers,
      desensitizes some neurons and has provided moderate pain relief when applied to
      the skin surface. Oral capsaicin in a candy (taffy) vehicle produced substantial
      pain reduction in 11 patients with oral mucositis pain from cancer therapy.
      However, this pain relief was not complete for most patients and was only
      temporary. Additional research is needed to fully utilize the properties of
      capsaicin desensitization and thus optimize analgesia.

PMID- 7629419
TI  - Reversible delirium in terminally ill patients.
AB  - Delirium is reported to be a common problem in terminally ill patients. The poor
      prognosis given to these patients may result in the failure to recognize the
      causes that are easily treated and may be reversible. We present four patients in
      whom a comprehensive assessment revealed a number of reversible causes of
      delirium, resulting in a treatment approach that significantly improved the
      patients' cognition and quality of life.

PMID- 7629420
TI  - Neuron-specific enolase (NSE) in serum. Comparison of monoclonal versus
      polyclonal assay based on 392 blood samples.
AB  - Neuron-specific enolase (NSE) is the best described serum tumor marker for small
      cell lung cancer (SCLC). Almost all clinical studies carried out so far used
      assays involving polyclonal antibodies against NSE; the majority of the studies
      analyzed the samples by a RIA NSE kit. We evaluated a new monoclonal kit and
      compared it to the polyclonal kit. We analyzed 392 serum samples, 265 from
      patients with SCLC, 88 from non-small cell lung cancers (NSCLC) and 39 from
      children with neuroblastomas. We found a good correlation between the results of
      the two assays. When correlating NSE in SCLC as measured with the two assays with
      clinical data, we found the same sensitivity, prognostic impact and value in
      treatment monitoring. We conclude that the "new" monoclonal assay is a fully
      acceptable alternative to the "old" polyclonal assay.

PMID- 7629421
TI  - DNA content in human colon cancer and non-neoplastic adjacent mucosa.
AB  - DNA content was determined by flow cytometry in a series of 51 paired fresh
      tissue samples of primary colorectal carcinomas and the respective non-neoplastic
      adjacent mucosa in order to assess the relationship between DNA ploidy and the
      most commonly used prognostic factors. Aneuploidy was observed in 70.6% of the
      tumors and more than one aneuploid peak was present in 3.9%. Aneuploid tumor
      frequency was higher in left (93.3%) and right colon (64.7%) cancers than in
      rectal carcinomas (60.0%), and multiple aneuploid clones were detected more
      frequently in men than in women and in patients with advanced disease (Dukes
      stage D). Non-neoplastic mucosa adjacent to aneuploid tumors showed aneuploidy in
      4 out of 51 samples (7.8%). The mucosa adjacent to diploid cancers had only
      diploid characteristics. Ploidy did not correlate with histological
      abnormalities. These findings suggest that DNA content as determined by flow
      cytometry needs further study with adequate follow-up to evaluate possible
      correlations with relapse-free and overall survival. Furthermore the aneuploidy
      of non-neoplastic mucosa provides evidence for a field defect in mucosa adjacent
      to colorectal cancer and supports the concept that this alteration may be of
      influence on carcinogenesis.

PMID- 7629422
TI  - Immunocytochemical determination of the tumor-associated glycoproteins MCA, CA
      125 and BW 495/36-P in urine of patients with epithelial tumors of the kidney and
      urinary bladder.
AB  - Pre-operative and, in some cases, post-operative urine samples from 29 patients
      with renal cell or urinary bladder carcinoma were compared to samples from 24
      healthy persons and 10 patients with nephrolithiasis and 9 patients with other
      benign disorders of the efferent urinary tract. The specimens were examined for
      the presence of MCA, CA 125 and BW 495/36-P expressing epithelial cells. The
      urine concentrations of the soluble antigens MCA and CA 125 were determined
      simultaneously in urine samples from 35 patients with renal cell or urinary
      bladder carcinoma, 10 patients with cystitis and 30 healthy individuals. MCA and
      BW 495/36-P expressing epithelial cells were significantly increased in all pre
      operative urine samples of the tumor patients compared to the group of healthy
      persons. This increase was also seen with CA 125-positive cells in patients with
      bladder carcinoma, not however in patients with renal cell carcinoma. BW 495/36-P
      positive cells were also found in both groups of tumor patients in greater
      numbers than in the patients with nephrolithiasis or other benign urinary tract
      disorders. Based on a specificity of 97% when compared to the control urine
      samples, the cytological determination of the antigens MCA, CA 125 and BW 495/36
      P in urinary tract cells of all tumor patients revealed a sensitivity of 48%, 33%
      and 79% as well as a positive predictive value of 92%, 89% and 95%, respectively.
      The sensitivity of CA 125 increased to 67% upon isolated analysis of patients
      with bladder carcinoma. The majority of labelled cells were not identifiable as
      tumor cells morphologically and appeared as normal transitional epithelial
      cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7629423
TI  - Study of serum tumor markers CEA, CA 15.3 and CA 27.29 as diagnostic parameters
      in patients with breast carcinoma.
AB  - Serum levels of CEA, CA 15.3 and CA 27.29 were measured during the follow-up of
      499 breast cancer patients. Studies included three different groups of women: 82
      blood donors free of disease, 42 patients with non-malignant breast diseases and
      499 breast cancer patients. After the determination of cut-off values, serum
      levels of tumor markers did not show significant elevations in benign breast
      diseases. On the basis of our results CA 15.3 (sensitivity = 57%; accuracy = 87%)
      was the most effective marker, CA 27.29 (sensitivity = 62%; accuracy = 83%) was
      the most sensitive and CEA (sensitivity = 45%; accuracy = 81%) was the least
      sensitive and effective marker. The combined use of markers was evaluated by step
      wise logistic regression analysis. The regression coefficients showed that CA
      15.3 (coeff. = 2.97) and CA 27.29 (coeff. = 1.46) were suitable for the detection
      of possible metastases during follow-up. Finally, we studied the relationship
      between pT, pN, pM and circulating levels of CA 15.3 and CA 27.29.

PMID- 7629424
TI  - Longitudinal follow-up of breast cancer patients with the tumor markers CA 549
      and CA 15.3.
AB  - In order to verify the efficiency of the tumor markers CA 15.3 and CA 549 in the
      follow-up of breast cancer patients, it was necessary first to check the cutoff
      levels of each tumor marker in women with an increased age-related risk, but with
      no evidence of disease. From 132 serum samples in this age group, we confirmed
      the CA 549 cutoff level of 12.1 U/ml. However, the cutoff of CA 15.3 was 34 U/ml,
      which is higher than previously reported in the literature. Fifty-two breast
      cancer patients with or without metastases at the time of entry into the study
      were followed for 2 to 3 years with both tumor markers. The sensitivity,
      specificity and the test efficiency for the presence of metastases were analyzed
      with each tumor marker. Taking into account the different cutoff levels, we
      concluded that both tumor markers can be used independently to follow the
      clinical situation of patients. In several cases an increase in both tumor
      markers was observed before a clinical diagnosis of metastases could be made.
      Combination of these two tumor markers gave no more significant information about
      the patient's clinical situation than each tumor marker alone.

PMID- 7629425
TI  - The clinical value of CEA and CA 15-3 in breast cancer management.
AB  - The value of tumour-associated antigens CEA and CA 15-3 was studied in patients
      with breast cancer over a 4-year period. A total of 252 patients with primary or
      recurrent disease had available and corresponding CEA and CA 15-3 values at
      diagnosis and during follow-up and were studied in detail. Preoperative and three
      monthly serial postoperative levels were measured in each patient. Ten of 11
      patients presenting with primary and concurrent metastatic disease had elevated
      CA 15-3 levels (> 25 I.U./ml) as compared to 6 with CEA (> 5 ng/ml). Fourty-seven
      patients developed locoregional recurrence of which 15 had concurrent metastatic
      disease. CA 15-3 was elevated in 14 cases while CEA in 11. Of 32 patients with
      locoregional recurrence alone, 18 later developed metastatic disease at a mean
      follow-up time of 17.5 months. There was a significant correlation between CA 15
      3 value at locoregional recurrence and time to subsequent metastasis (r = 0.
      0.57, P = 0.0133). CEA was elevated in 64%, CA 15-3 in 87% and either marker in
      94% of 87 patients diagnosed with metastatic disease. Of 53 patients with serial
      markers and metastatic disease, 72% (38/53) had rising CA 15-3 levels prior to
      diagnosis with a mean lead time of 9.9 months. Use of CEA in conjunction improved
      lead time detection to 83%. This study demonstrates that CA 15-3 is superior to
      CEA at detecting metastatic disease at initial presentation and during follow-up.
      Use of CEA in conjunction with CA 15-3 improves the detection of systemic
      disease.

PMID- 7629426
TI  - Skeletal alkaline phosphatase as a serum marker of bone metastases in the follow
      up of patients with breast cancer.
AB  - Immunoradiometric determination of the bone isoenzyme of alkaline phosphatase
      with a method provided by Hybritech Inc., San Diego CA (USA) was carried out in
      145 female patients, 97 of whom with radically operated breast cancer and 48 with
      benign mammary cysts, in order to evaluate the correlation of serum levels with
      the metabolic process of bone rearrangement in patients with bone metastases.
      This study shows that skeletal ALP, having high specificity (86.48%) and
      sensitivity (78.6%) for early progression (the average anticipation time compared
      to scintigraphic detection was 101 days) could represent a valid marker for bone
      metastases in association with mucinous markers in the follow-up of patients
      operated for breast cancer. In addition, dynamic serum determination of skeletal
      ALP could be a valid help in monitoring the efficacy of therapy in patients with
      bone progression.

PMID- 7629427
TI  - Progesterone agonists and antagonists induce down- and up-regulation of estrogen
      receptors and estrogen inducible genes in human breast cancer cell lines.
AB  - The effects of the synthetic progestin R5020 and the antiprogestin RU486 on the
      cellular content of estrogen receptors (ER) and on cell responsiveness to
      estrogens, have been investigated in the sex hormone-sensitive human breast
      cancer cell lines MCF-7 and T47D. When T47D cells were treated with R5020
      (Promegestone) (10(-8) M), ER was down-regulated to about 50% of the control
      level in a time-dependent manner. Maximum down-regulation was observed after 24
      hours and remained at this level for the next 24 hours. Dihydrotestosterone (DHT)
      or dexamethasone (DEX) had no effect on ER sites. R5020 also down-regulated,
      although to a lesser extent, ER in the MCF-7 cells which contain fewer
      progesterone receptor (PR) sites. When MCF-7 cells were transfected with a
      progesterone receptor expression vector (tMCF-7) to increase the number of PR
      sites, R5020 down-regulated the ER to a level similar to that reached in T47D
      cells. In both cell lines ER down-regulation was completely inhibited by a 10
      fold molar excess of the antiprogestin RU486 (Mifepristone) (10(-7) M).
      Surprisingly, when incubated with RU486 alone, T47D cells responded by up
      regulating ER 2-4 fold. The functional relevance of inhibition and up-regulation
      of ER for the estrogen responsiveness of hormone-sensitive human breast cancer
      cells was tested by assaying the synthesis of an estrogen-regulated product, the
      PS2 protein. Estrogen induction of this protein was inhibited by at least 70% in
      T47D cells exposed to R5020 for 24 hours before estrogen administration and by
      about 25% in MCF-7 cells under the same conditions.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7629428
TI  - Serum CEA, CA125, and SCC antigens and tumor recurrence in resectable non-small
      cell lung cancer.
AB  - Carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC), and CA125
      were determined pre- and postoperatively in non-small cell lung cancer patients
      (NSCLC) to assess the relationship between serum levels and postoperative
      recurrent disease. Ninety-five patients who underwent curative surgical resection
      were included (TNM stages I, II, IIIa). CEA and CA125 were determined by solid
      phase enzyme-immunoassay, SCC by radio-immunoassay. Tumor relapse was detected in
      41 patients (43%): 16 (39%) with locoregional disease and 25 (61%) with
      disseminated disease. The overall 36-month disease-free survival rate was 42%.
      The sensitivity for recurrence was 58% for CEA, 53.6% for CA125, and 51.2% for
      SCC; 87.8% of patients showed at least one elevated marker. The sensitivity of
      CEA and CA125 increased significantly in patients with preoperative serum
      concentrations above the cut-off: 86.6% versus 42.3% (p < 0.01), and 93% versus
      18% (p < 0.01), respectively. Preoperative CA125 above 15 U/ml identified a high
      risk group of patients: a lower 36-month disease-free survival rate (0% versus
      56%) (p < 0.001), a 3.02-fold higher risk of recurrence (p < 0.05), and a 6.22
      fold higher risk of disseminated failure (p < 0.001). The identification of CEA
      and CA125 producer-tumors, based on preoperative serum values, enhances the
      clinical performance of a postoperative surveillance program in surgically
      treated NSCLC. Preoperative serum CA125 is a prognostic factor to identify
      patients at high risk of postoperative tumor recurrence.

PMID- 7629429
TI  - Eosinophilia induced by interleukin-2 cancer immunotherapy may be associated with
      enhanced production of total IgE.

PMID- 7629430
TI  - Effects of granulocyte colony stimulating factor on the specific macrophage
      marker neopterin in cancer patients.

PMID- 7629431
TI  - Energy deposition events produced by fission neutrons in aqueous solutions of
      plasmid DNA.
AB  - Using an agarose gel electrophoresis assay, single-strand breaks (ssb) induced by
      fission neutrons and 60Co gamma-rays in aerobic aqueous solutions of pBR322
      plasmid DNA were studied. The energy-deposition events of the two radiations were
      characterized using a Rossi-type proportional counter to measure lineal-energy
      spectra. For neutrons, the dose-weighted lineal-energy mean, yD, is 63 keV micron
      1--about 30 times that for gamma-rays. With increasing yD, hydroxyl radicals
      produced within spurs or tracks are less likely to survive due to recombination
      effects, resulting in decreased ssb yields. In TE buffer solution, the ssb yield
      induced by gamma-rays is 3.2 +/- 0.66 times that induced by neutrons at the same
      dose. Since the direct radiation effect is small under these conditions, we can
      estimate that the previously unknown G for hydroxyl radical production by fission
      neutrons is 0.088 mumol J-1. For glycerol concentrations that give the solution a
      hydroxyl radical scavenging capacity similar to that of cellular environments,
      the ssb yield induced by gamma-rays is about 2.0 +/- 0.24 times that induced by
      neutrons. Analysis shows that this trend with added scavenger is caused primarily
      by hydroxyl radical yields.

PMID- 7629433
TI  - Frequency of micronucleated-binucleated lymphocytes is not significantly affected
      by the harvest time following G0 exposure to X-radiation.
AB  - Whole blood from two male individuals was X-irradiated using a linear accelerator
      at 200 cGy/min to give a total exposure of 300 cGy. Lymphocytes were cultured
      using standard techniques with the addition of 3 micrograms/ml cytochalasin B at
      26 h to produce binucleation through the inhibition of cytokinesis for the
      scoring of micronuclei after the first nuclear division. Replicate cultures from
      each individual were harvested at 48, 68, 70, 72, 74, 76, 92, 94, 96, 98 and 100
      h postinitiation using a cytocentrifuge. Slides were stained with acridine
      orange, and binucleated cells were scored for the presence of micronuclei. There
      were no statistically significant differences in the frequency of micronucleated
      binucleates between replicate cultures, between individuals, or among cultures
      harvested from 48 to 100 h postinitiation. This indicates that the
      phytohaemagglutinin-stimulated lymphocytes are a relatively homogeneous
      population of cells with respect to X-radiation-induced chromosome damage. In
      addition, these data show that for determining the frequency of micronuclei in
      lymphocytes irradiated in G0, the harvest time (up to at least 100 h
      postinitiation) is not critical as long as analysis is confined to the first
      mitosis after irradiation (i.e. the binucleated cells).

PMID- 7629432
TI  - Chromatin structure and radiation-induced DNA strand breaks in human cells:
      soluble scavengers and DNA-bound proteins offer a better protection against
      single- than double-strand breaks.
AB  - In the present investigation we have studied the formation of DNA double-strand
      breaks (dsbs) in different chromatin substrates and made a comparison with our
      previous results on radiation-induced single-strand breaks (ssb). Removal of
      soluble scavengers increased the number of ssbs by a factor of 2, but increased
      dsbs only 1.2 times. Decondensation of the chromatin increased ssbs and dsbs to
      the same extent, by a factor of 3-4. Removal of DNA-bound proteins gave an
      additional increase in ssbs and dsbs by a factor of 14 and 5 respectively. The
      increase in both ssbs and dsbs was caused by OH radicals. The differential effect
      on ssbs and dsbs can be explained by assuming that dsbs are formed mainly by
      multiple hits from clusters of ionizations close to the DNA. When the DNA-bound
      proteins are removed, more distant radicals can reach the DNA, which favours ssb
      formation. Under those conditions dsbs also induced by single OH radicals become
      important. DNA-bound proteins protect DNA only to a limited extent by acting as
      scavengers of OH radicals. The largest part of the protection depends on the fact
      that DNA in the chromatin is made up of large, compact aggregates, where the
      distance between separate aggregates exceeds the effective range of the OH
      radicals and the amount of water inside the aggregates is too small to give a
      maximal contribution of OH radicals compared with when DNA is more evenly
      distributed in a given volume.

PMID- 7629434
TI  - Combined FISH painting and harlequin staining for cell cycle-controlled
      chromosome analysis in human lymphocytes.
AB  - We present a simple method that allows scoring of FISH-painted chromosomes
      exclusively in the first division human lymphocytes. It consists of a combination
      of FISH with chromosome-specific libraries and a differential sister chromatid
      staining after BrdU treatment of lymphocyte cultures. The method allows a precise
      quantification of induced chromosome damage for human biodosimetry.

PMID- 7629435
TI  - Thymidine free radicals generated during metallo-phthalocyanine
      photosensitization: a comparison with gamma-radiation.
AB  - In order to obtain information concerning the mechanism(s) of metallo
      phthalocyanine (MePcS4) photosensitized damage of DNA constituents, the EPR-spin
      trapping method in conjunction with liquid chromatography was used to study
      thymidine (dThd) free radicals formed during photosensitization or exposure to
      gamma-radiation in solution. Under specified conditions two dThd free radical
      species, 5-hydroxy-5,6-dihydrothymidine-6-yl and 6-hydroxy-5,6-dihydrothymidine-5
      yl, were formed both during exposure to ionizing radiation and
      photosensitization. These results imply that identical reactive intermediates
      (*OH radicals) are involved in the radiolytic and photosensitized oxidation of
      dThd. A light-dependent, Fenton-type mechanism is proposed to explain the
      generation of hydroxyl radicals during MePcS4 photosensitization.

PMID- 7629436
TI  - Photofrin photosensitization. Correlation of Photofrin:erythrocyte binding
      processes with photolysis.
AB  - Unilamellar suspensions of dimyristoylphosphatidylcholine (DMPC) can be utilized
      to remove Photofrin from the erythrocyte. This enables correlation of the
      Photofrin membrane-binding processes with Photofrin-sensitized photolysis. The
      observed rates of erythrocyte biding as well as the observed rates of removal of
      PHotofrin from the erythrocyte membrane suggest the existence of two Photofrin
      species that differ in their rates of exchange between the erythrocyte and buffer
      phases. Selective depletion and readdition of these Photofrin species to the
      erythrocyte membrane permits evaluation of their separate and joint photolytic
      efficiencies. These rapidly and slowly exchanging membrane-bound Photofrin
      species are separately much less efficient photosensitizers than the two species
      together. The two Photofrin species exhibit essentially identical fluorescence
      emission spectra in the presence of DMPC. Nevertheless, models consistent with
      the results involve partitioning by chemically distinct Photofrin components or
      partitioning of chemically similar Photofrin components into distinct membrane
      environments, or a combination of these.

PMID- 7629437
TI  - Oral administration of tritiated water (HTO) in mouse. II. Tumour development.
AB  - Previously we reported haematopoietic death as an effect of tritiated water (HTO)
      in drinking water in the concentration range from 5.92 x 10(11) to 1.85 x 10(10)
      Bq/dm3. In the present study the effects of HTO in a lower concentration range
      from 9.25 x 10(9) Bq/dm3 (0.240 Gy/day) to 3.70 x 10(8) Bq/dm3 (0.096 Gy/day) are
      reported. Female (C57BL/6N and C3H/He)F1 mice were maintained on drinking water
      containing various levels of HTO. Mice survived for > 150 days with a high
      incidence of tumour development (70 to 80%). In the dose-rate range from 9.25 x
      10(9) Bq/dm3 (0.240 Gy/day) to 1.85 x 10(9) Bq/dm3 (0.048 Gy/day) the main cause
      of death was thymic lymphoma. However, at a dose-rate of 9.25 x 10(8) Bq/dm3
      (0.024 Gy/day) the incidence of thymic lymphoma sharply decreased, while the
      incidence of other tumours increased. The tumour type became more diverse at
      lower concentrations of HTO. The latent period of tumour development was shorter
      and the life-shortening effect was more marked by 3H beta-irradiation in this
      study than b X- or gamma-irradiation reported in other investigations.

PMID- 7629438
TI  - Intranuclear sites of Np 237 in mammalian cells: a study using electron
      microscopy and electron probe microanalysis.
AB  - Two methods, electron microscopy and wavelength dispersive electron probe
      microanalysis, were used to determine the intracellular sites and chemical form
      of concentrations of neptunium nitrate 237 after chronic intoxication by the
      intraperitoneal route in two organs in the rat known to concentrate this element
      (kidney, liver). Abnormal intranuclear formations in the form of clusters of
      dense granules containing neptunium, phosphorus, sulphur, and calcium were found
      in the nuclei of kidney proximal tubule cells and hepatocytes. These formations
      had a maximum diameter of the order of 2 microns and were located in the central
      part of the nucleus, away from the nucleolus and peripheral chromatin. Serious
      nuclear and cytoplasmic ultrastructural lesions are often associated in cells
      containing neptunium inclusions. The absorbed doses in the kidney and the liver
      were very low. A relationship between these abnormal intranuclear structures and
      the carcinogenic effect of neptunium remains to be clarified. This effect is
      related more probably to the chemical toxicity of Np 237.

PMID- 7629439
TI  - Examination of testicular tumours in the beagle dog exposed to inhaled plutonium.
AB  - Gross and light microscopic features of testicular neoplasms were examined in the
      male beagle dog used in three studies to examine the life-span effects of inhaled
      plutonium (Pu). One hundred and sixty-six cases of testicular neoplasia (TN)
      occurred among 105 dogs that ranged in age from 7.5 to 17.7 years at the time of
      diagnosis. The 166 cases of TN comprised 113 interstitial cell tumours, 27
      seminomas in situ, 19 seminomas, and seven Sertoli cell tumours. Serum
      testosterone and estradiol 17-beta concentrations, and the serum testosterone-to
      oestradiol ratio were determined in 39 dogs with TN and in five clinically
      normal, sexually intact, age-matched cohorts. Serum hormone concentrations did
      not differ significantly among tumour types or between dogs with neoplasms and
      age-matched cohorts. There was a significant relationship between initial lung
      deposition (ILD) of Pu and activity in the testis (Bq/g testis). The slope of the
      relationship was 0.35, 0.89 and 0.91 for 239PuO2, 238PuO2 and 239Pu(NO3)4
      respectively. Pu in the testis at long times (> 5 years) after inhalation was
      between 0.0001 and 0.03% ILD, depending on the physicochemical form of Pu.
      Although the mean activity of Pu in the testis of dogs was higher in those life
      span studies employing 238PuO2 and 239Pu(NO3)4, the cumulative proportion of dogs
      with tumours, the distribution of tumour types, and mean time to first tumour was
      not significantly different among the three studies or dose groups, including
      controls, within a study.

PMID- 7629440
TI  - Ultrastructural morphometric analysis of peripheral nerves after intraoperative
      irradiation.
AB  - Intraoperative irradiation (IORT) is used to enhance local tumour control by
      using large, single doses while removing critical structures from the treatment
      field. Peripheral nerve remains a dose-limiting normal tissue that often cannot
      be removed from the field. To assess ultrastructural changes in canine sciatic
      nerve after IORT, computerized morphometric analysis of plastic sections and
      electron micrographs of nerve cross-sections was used. Surgically exposed sciatic
      nerves were irradiated with 6 MeV electrons to 12, 20 or 28 Gy. Twelve months
      after treatment dogs were killed humanely and the nerves from three dogs per dose
      group, including non-irradiated controls, were analyzed. Twelve months after 28
      Gy IORT a significant decrease in nerve fiber density occurred. Nerve fiber loss
      was particularly prominent in the central portion of the nerve predominantly
      among large nerve fibers. Other nerve fiber parameters including fiber and axon
      area, diameter and perimeter, myelin thickness, form factor (measure of
      roundness), and G ratio (axon diameter/fiber diameter) did not show significant,
      dose-related changes. An increase in microtubule and neurofilament density in
      irradiated nerve axons was found. These changes are suggestive of radiation
      induced hypoxia (damage to microvasculature) resulting in axon damage and
      subsequent nerve fiber loss as a possible mechanism of late radiation injury to
      peripheral nerve.

PMID- 7629441
TI  - Protein alterations in the skin of the mouse with radiation-induced
      gastroschisis.
AB  - We have used two-dimensional gel electrophoresis to analyse proteins in the skin
      of mouse foetuses with and without gastroschisis after X-irradiation of embryos
      during the one-cell stage. An increased phosphorylation of two proteins and a
      shift in one glycoprotein were observed in the skin of irradiated foetuses with
      gastroschisis compared with the unirradiated normal controls. These protein
      changes are specifically associated with this malformation. We discuss the
      results in terms of mutations related to the irradiation of the one-cell embryo.

PMID- 7629442
TI  - Long-term consequences of high-dose total-body irradiation on hepatic and renal
      function in primates.
AB  - Radiation effects in non-human primates were studied in order to define the long
      term risk of total-body irradiation (TBI) for bone marrow transplantation
      patients. The long-term effects of TBI could be investigated by keeping 84
      monkeys of different ages, from an experiment on acute effects, under continuous
      observation for a period up to 25 years. The control group consisted of non
      irradiated monkeys with a comparable age distribution and identical housing
      conditions. Since radiation was the common toxic agent, the different age groups
      provided the possibility to investigate the occurrence of deterministic effects
      after TBI. In the present study emphasis was placed on the assessment of hepatic
      and renal function and the associated histopathology. The values of the liver
      function parameters, such as alkaline phosphatase and gamma glutamyl transferase
      in the irradiated group were significantly increased after TBI (p < 0.05). Also
      the parameters of kidney dysfunction, e.g. haematocrit and blood urea nitrogen
      showed a significant change in the irradiated old-aged (post-irradiated interval
      > 15 years) cohort (p < 0.005). The impairment of the liver and renal functions,
      did not lead to clinical symptoms and were only associated with mild morphologic
      changes in the irradiated group of monkeys. In the population of bone marrow
      transplant patients treated with TBI, alterations in hepatic and renal function
      parameters after a post-irradiated interval of > 10 years can be anticipated.
      This could have consequences for the tolerance and toxicity of a broad range of
      drugs to be administered as additional medications.

PMID- 7629443
TI  - Neutron spectrum and yield of the Hiroshima A-bomb deduced from radionuclide
      measurements at one location.
AB  - In this paper measurements of the radionuclides of 36Cl, 41Ca, 60Co, 152Eu and
      154Eu in samples from Hiroshima, which were exposed to neutrons of the A-bomb
      explosion, are interpreted. In order to calculate the neutron spectrum at the
      sample site, neutron transport calculations using Monte Carlo techniques were
      carried out. Activation profiles in a granite mock-up irradiated with reactor
      neutrons could be reproduced by this method using DS86 input parameters. The
      calculated neutron spectrum at the sample site for non-thermal neutrons is
      identical to that obtained in DS86, but contains some 50% more thermal neutrons.
      The influence of parameters like soil composition, source terms and air humidity
      on the activation of these radioisotopes is discussed. The granite-covered earth
      at the sample site, for example, hardens the spectrum in comparison with DS86
      values. Even when using a fission spectrum pointing downward and neglecting air
      humidity one cannot explain our 36Cl measurements. If the effective thermal
      neutron fluences, that have a similar ratio of resonance integral to thermal
      neutron capture cross sections obtained from 36Cl, 41Ca and 152Eu, are averaged,
      a bomb yield of about 16 kt is deduced in agreement with a bomb yield of (15 +/-
      3) kt estimated in DS86.

PMID- 7629445
TI  - An infant with Down-Turner double aneuploidy: a case report and literature
      review.
AB  - The case of an 8 month-old female infant with non-mosaic Down-Turner double
      aneuploidy is reported. She had Down facies without stigmata of Turner syndrome.
      A review of 22 previous reported cases revealed mosaicism in all cases, either 21
      mosaic or X mosaic. Our patients is the first reported case of non-mosaic trisomy
      21-monosomy X polysyndrome in Thailand.

PMID- 7629444
TI  - Metaplasia of bone in lungs and bronchi: report of 2 cases.
AB  - Two cases are reported of pulmonary osseous metaplasia in elderly men aged 91 and
      64 years. The first case represented disseminated metaplastic bones occurring
      throughout the lungs. In the second instance, small foci of metaplastic bones
      were localized in some bronchial walls of the upper lobe of the right lung which
      had old treated tuberculosis, severe fibrosis, and bronchiectasis. Both cases
      also had advanced pulmonary emphysema and interstitial fibrosis. It is suggested
      that fibrosed interstitium of the lungs and bronchial walls has turned into bony
      metaplasia in both patients. However, osseous metaplasia from cartilage of the
      bronchial walls is additionally suggested in case 2. Multiple factors probably
      play roles in development of bony metaplasia.

PMID- 7629446
TI  - Environmental surveillance of Legionella species in Thailand.
AB  - Legionellae was found in 57 per cent of 94 cooling towers and 21.8 per cent of 78
      other environmental sources. These figures reveal that the existence of
      legionellae in cooling towers is more prevalent than that found in other
      environmental sources. Legionella pneumophila serogroup 1 was the most prevalent
      organism among the legionellae found in cooling towers and other environmental
      sources. The recovery of legionellae in each province was seasonally independent
      and was found throughout the year. This is the first report of an environmental
      survey representing the existence of legionellae in every region of Thailand.

PMID- 7629447
TI  - Etiology of erythema nodosum.
AB  - One hundred patients with biopsy-proven erythema nodosum were studied at
      Ramathibodi Hospital from 1982 to 1992 to find out the etiology of this disease.
      Eighty-eight were females while twelve were males, with an age range from 6 to 72
      years old (mean, 31 years old). Abnormal laboratory findings in these patients
      included elevation of erythrocyte sedimentation rate (76.9%), increase anti
      streptolysin-O titer (10.7%), abnormal chest roentgenogram (16.7%), positive
      tuberculin test (50%). The cause of erythema nodosum is still unknown in a large
      group of patients, and it was found only in twenty-eight patients (28%). Twelve
      patients had tuberculosis, seven had history of antibiotic administration, six
      probably had streptococcal infection and the other three had Behcet's disease.

PMID- 7629448
TI  - Intravenous nicardipine for the treatment of severe hypertension. A dose
      titration infusion to therapeutic response.
AB  - Intravenous nicardipine titration, starting with 10 mg/hr and increased slowly
      every 4 minutes by the rate 1 mg/hr until target supine DBP of 90 mmHg was
      achieved, was a very effective and safe method for patients with very severe
      hypertension. All patients had their BP under good control with few adverse
      effects. Although the heart rate rose significantly there were only four cases
      with palpitation and one case with chest pain which spontaneously recovered
      without sequele.

PMID- 7629449
TI  - Evaluation of sperm nuclear DNA normality by acridine orange staining technique.
AB  - To determine the relationship between sperm deoxyribonucleic acid (DNA) normality
      and fertilizing potential, 93 semen samples from 48 fertile donors and 45 male
      partners of infertile couples whose major abnormalities in the female partner had
      been ruled out were studied. Semen samples were assessed for conventional
      parameters (volume, percentage of normal morphology, percentage of progressive
      motility, sperm concentration, and round cell concentration) according to World
      Health Organization (WHO) guideline and acridine orange staining. The mean sperm
      concentration, percentages of progressive motility, and percentage of green
      fluorescing sperm in semen were significantly higher in samples from fertile
      donors (p < 0.005). When the parameters of semen quality were considered normal
      according to the standard WHO criteria, the mean percentages of green-fluorescing
      sperm were significantly higher in fertile donors than infertile patients (65.6%
      vs 53.3%; p < 0.05). Therefore, the acridine orange staining technique for
      evaluation of the sperm DNA normality appears to give more information in
      infertile patients with normal semen analysis. It may be a useful addition to the
      conventional semen analysis.

PMID- 7629450
TI  - Relationship between the direct mixed antiglobulin reaction (MAR) test and
      spontaneous sperm agglutination in men from infertile couples.
AB  - To determine the relationship between the direct MAR test and spontaneous sperm
      agglutination in men from infertile couples, semen samples from 160 men were
      studied. Spontaneous sperm agglutination was present in 80 samples, and absent in
      the others. Routine semen analysis and the direct MAR test were performed on all
      samples. The incidence of positive MAR tests in samples with and without
      spontaneous sperm agglutination were 15 and 0 per cent respectively (p < 0.05).
      There were no significant differences in mean sperm concentration, motility, and
      morphology between the samples with and without spontaneous sperm agglutination,
      and between the positive and negative MAR test groups. It can be concluded that
      spontaneous sperm agglutination relates significantly to antisperm antibodies
      detected by the direct MAR test, and this factor could be used as indication for
      antisperm antibody testing of infertile men.

PMID- 7629451
TI  - The impact of routine preoperative urinalysis in Srinagarind Hospital, Khon Kaen.

PMID- 7629452
TI  - Intrathoracic lymphangiohemangioma associated with hemothorax: a cause of
      intrauterine fetal death.
AB  - A case is presented of a large intrathoracic lymphangiohemangioma in association
      with spontaneous hemothorax. The lesion was found in a macerated stillborn
      infant. The precise nature of the tumor was documented histologically.

PMID- 7629453
TI  - Getting research into practice.

PMID- 7629454
TI  - Can general practice provide useful information?--evaluation of a primary health
      care information project in northern England.
AB  - OBJECTIVE: To develop a computerised primary care information gathering network
      capable of producing reliable risk factor and morbidity data from a wide
      diversity of general practice software systems. METHOD: Fourteen practices from
      the Wakefield and Pontefract district collaborated in sharing information and
      solving technical difficulties associated with collecting data on coronary heart
      disease (CHD) risk factors, diabetes, and asthma. Practices also participated in
      rheumatology and mental health needs assessment projects. RESULTS: Data could be
      transferred by diskette in only five of the systems and paper reports had to be
      used to post process the data into a standard format. Not all data were complete
      or comparable. Crude estimates only of smoking prevalence and smoking cessation
      interventions were possible, as well as of age and sex specific prevalences for
      asthma and diabetes. The rheumatology health needs assessment, using the
      prospective collection of consultation based data, highlighted an unmet need for
      rheumatology services in the community. CONCLUSIONS: Although practices have been
      willing to devote considerable time and effort to the project, the diversity of
      software has precluded a simple methodology for data collection and analysis. The
      amount of useful information retrieved so far, has been limited but a number of
      important lessons have been learned which have implications for similar
      information projects and the use of primary care information in service planning.

PMID- 7629455
TI  - Rotterdam general practitioners report (ROHAPRO): a computerised network of
      general practices in Rotterdam, The Netherlands. Rotterdam's HuisArtsen Project.
AB  - STUDY OBJECTIVE: Dutch public health services are charged with collective
      preventive care for the population--care that should, by law, be based on
      epidemiological data. General practices potentially offer important data for this
      purpose, particularly since more and more use a computer. This study aimed to
      assess whether it is possible to obtain useful epidemiological data from this
      source. DESIGN: In 1990, the Rotterdam Municipal Health Service, in collaboration
      with the Erasmus University Rotterdam, started a computerised sentinel practice
      network. The main features of this and a specific small investigation are
      described. SETTING: The following institutions cooperate in the network:
      Municipal Health Service Rotterdam Area; Departments of General Practice and of
      Medical Informatics, Erasmus University Rotterdam; Rotterdam District Association
      of General Practitioners. PATIENTS: Data are currently collected from 20 general
      practitioners and > 40,000 patients. In a specific project, the distribution of
      cardiovascular risk factors in different ethnic groups was compared. MAIN
      RESULTS: It was possible to build up a regional epidemiological registration
      system in this manner. In the cardiovascular project we found striking
      differences between ethnic groups. The risk profile for Turkish men, in
      particular, was less favourable. The health service also uses the system to
      improve cooperation between public health and primary health care (for example,
      in cervical screening, influenza vaccination). CONCLUSION: Computerised general
      practices offer great possibilities for research and for preventive activities in
      which public health care and general practitioners can cooperate.

PMID- 7629456
TI  - Surgery for glue ear: the English epidemic wanes.
AB  - OBJECTIVES: To describe the progress of the epidemic of surgery for glue ear
      since 1983 and trends in the use of different operative procedures. DESIGN:
      Analysis of routine hospital data. SETTING: Thirteen health districts in the
      Oxford and East Anglian regions. MAIN MEASURES: Annual rates of surgery in
      children under 10 years of age. RESULTS: The rate of surgery for glue ear reached
      a peak in 1986 since when it has declined by 12.6%. The rate peaked in all 13
      districts but at different times over a six year period (1984-1989/90). Following
      the peak, district rates plateaued in eight districts and declined in five. These
      changes have been accompanied by: an increase in the proportion of operations
      confined to the tympanic membrane since 1983 (from 40% to 60%); an increase in
      the use of grommets after myringotomy (from 50% to 94% since 1980); and an
      increased use of day surgery for ear-only operations (from about 10% in the late
      1970s to 50% in 1987/88). CONCLUSIONS: The previously reported epidemic of
      surgery for glue ear is waning. This seems to be a result of changes in the
      clinical judgment of general practitioners and surgeons as to its use and
      possibly of a reduced demand from parents.

PMID- 7629457
TI  - Hepatitis B vaccination: the cost effectiveness of alternative strategies in
      England and Wales.
AB  - OBJECTIVE: To assess the cost effectiveness of adding universal hepatitis B
      vaccination in infancy or pre-adolescence to a policy of selective vaccination of
      at risk groups. DESIGN: Costs of a selective policy and additional costs of
      universal vaccination policies were estimated from costs of vaccine delivery and
      published data on target populations. Additional years of life gained were
      calculated for each policy by applying life tables to estimates of mortality
      attributable to hepatitis B. SETTING: England and Wales. RESULTS: Compared with
      no vaccination, vaccination in infancy was the most cost effective followed by
      vaccination in preadolescence. Selective vaccination was the least effective
      (cost per year of life gained 2568 pounds, 2824 pounds, and 8564 pounds
      respectively). Adding vaccination in infancy or at pre-adolescence to a selective
      policy cost 1537 pounds or 1658 pounds per year of life gained. Discounting years
      gained in the future at 6% per annum, however, made pre-adolescent vaccination
      more cost effective than infant or selective vaccination (51,817 pounds, 94,821
      pounds, and 124,779 pounds per discounted year of life gained). Adding pre
      adolescent vaccination to a selective policy cost 32,125 pounds per discounted
      year of life gained and infant vaccination, 77,085 pounds. CONCLUSIONS: Universal
      vaccination against hepatitis B was more cost effective than selective
      vaccination in a low prevalence country. Discounting future health gain, however,
      made universal infant vaccination lest cost effective than universal pre
      adolescent vaccination. If future health gained is as important as present gain
      the addition of universal vaccination to a selective policy is equivalent to the
      cost per quality adjusted year of life from renal transplantation or breast
      cancer screening.

PMID- 7629458
TI  - Infant mortality and famine: a study in historical epidemiology in northern
      England.
AB  - OBJECTIVE: To examine whether periodic variations in annual infant mortality were
      associated with malnutrition and the poor quality of the food supply available to
      the community. DESIGN: Retrospective study of historical epidemiology of infant
      mortality by time series analysis and family reconstitution of parish registers
      of burials and baptisms. SETTING: Penrith, Cumbria, England, 1557-1812. SUBJECTS:
      A total of 17,500 births during 1557-1812. RESULTS: This community in the Eden
      Valley, Cumbria, close to the Scottish borders, was living under marginal
      conditions with high mortality and low fertility. Clear oscillations in infant
      mortality synchronise with the oscillations in the wheat price index which is
      regarded as a measure of the availability of food to the community, and to
      pregnant and nursing mothers in particular. Input-output analysis showed that the
      relationship between the wheat price index (input) and infant mortality (output)
      was highly significant (p < 0.001). Events during the famine of 1623 have been
      analysed in detail: high wheat prices during pregnancy caused subsequent severe
      infant mortality but did not have indirect effects on the subsequent mortality of
      the surviving children over the age of 1 year. Non-stationary oscillations in
      neonatal and post neonatal mortality were strongly coherent (p < 0.001) with the
      wheat price index throughout the period. CONCLUSIONS: Infant mortality is
      particularly sensitive to famine and also to the quality of the food supply
      available to pregnant and nursing mothers. The lags between neonatal and post
      neonatal mortalities and wheat prices, together with the analysis of the famine
      of 1623, support the hypothesis that neonatal mortality was related to
      malnutrition in pregnancy whereas post-neonatal mortality was primarily directly
      dependent on exogenous causes in the first year of life.

PMID- 7629459
TI  - Risk factors in clinically diagnosed presenile dementia of the Alzheimer type: a
      case-control study in northern England.
AB  - STUDY OBJECTIVE: To investigate the relationship between presenile dementia of
      the Alzheimer type (PDAT) and family history, medical history, cigarette smoking,
      and exposure to aluminum. DESIGN: A case-control study in which 109 cases of
      clinically diagnosed PDAT and 109 controls matched for age and sex were compared
      for exposure to the risk factors. Odds ratios (ORs) were calculated using
      McNemar's test. SETTING: The northern health region of England. PATIENTS: Cases
      comprised those under 65 years diagnosed as having dementia by specialist
      services, who met clinical algorithm criteria for Alzheimer's disease (AD). Cases
      were confirmed at interview. MAIN RESULTS: Comparing cases with controls, (ORs)
      significantly greater than unity were obtained when there was a first degree
      relative with dementia (OR 2.5, 95% confidence interval 1.05, 6.56), any relative
      with dementia (OR 2.1, 95% CI 1.01, 4.55), and any relative aged less than 65
      with dementia (OR 8.0, 95% CI 1.07, 348). Exposure to moderate levels of
      cigarette smoking (cumulative) was not significant; nor was exposure to aluminum
      in drinking water, diet, and medicinal sources. CONCLUSION: In this study of
      modest statistical power, a family history of dementia was confirmed as a risk
      factor in PDAT. No significant relationship between exposure to aluminium in
      water supplies, tea, and antacids was found. What is important, however, is the
      bioavailability of all dietary aluminium, determined by the concentrations of
      dissolved silicon in water: this requires further investigation.

PMID- 7629460
TI  - Body fat and stroke: unmasking the hazards of overweight and obesity.
AB  - STUDY OBJECTIVE: It has been frequently noted that overweight and obesity have a
      stronger relationship to hypertension and diabetes mellitus than to the risk of
      stroke. The reason for this observation has not been clear. This study aimed to
      examine the lifelong relation between body fat and stroke to shed light on why
      the public health risks of overweight and obesity have tended to be obscured in
      previous epidemiological studies. DESIGN: Case-control study. SETTING: Eleven
      general practices in west Birmingham. PARTICIPANTS: Altogether 125 men and women
      who had just had their first stroke and were aged 35-74 years and 198 controls
      frequency matched for age and sex were recruited over 24 months during 1988-90.
      MAIN RESULTS: Those in both the thinnest and fattest quartiles of subscapular
      skinfold thickness were at increased risk of stroke compared with those in the
      middle quartiles (age adjusted odds ratios 2.12 (95% confidence interval (CI)
      1.2, 3.9) and 2.08 (1.1, 3.8) respectively). When lifelong maximum reported body
      mass index was assessed the hazards of obesity but not leanness were seen (odds
      ratio for the highest versus the lowest quartile were--age adjusted, 1.54 (0.8,
      3.0) and multiple risk factor adjusted, 2.25 (1.1, 4.5). This lifelong pattern of
      risk seemed to be established early, the odds ratios for the highest versus the
      lowest quartile of reported body mass index aged 21 years were--age adjusted,
      2.18 (1.1, 4.4) and multiple risk factor adjusted 2.13 (1.1, 4.2). The risks of
      both maximum reported body mass index and reported body mass index aged 21 years
      were more clear in those who had never smoked cigarettes (test for trend in odds
      ratio, p = 0.009 and p = 0.02 respectively). CONCLUSIONS: Potentially important
      risks of excessive body fat for stroke can be obscured by both a history of
      cigarette smoking and thinness associated with deteriorating health. The results
      seem to explain why excess body fat has previously been consistently related to
      hypertension and diabetes mellitus but less consistently to stroke. Avoiding
      overweight and obesity during adult life offers protection against stroke.

PMID- 7629461
TI  - Body mass index and cardiovascular mortality at different levels of blood
      pressure: a prospective study of Norwegian men and women.
AB  - STUDY OBJECTIVE: The study investigated the joint effect of body mass index and
      systolic blood pressure on cardiovascular and total mortality. DESIGN: This was a
      prospective cohort study. The main outcome measures were age adjusted mortality
      and relative risks estimated from survival models. SETTING: The population of the
      city of Bergen, Norway. PARTICIPANTS: Subjects were 21,145 men and 30,330 women
      aged 30-79 years at the time of examination in 1963. MAIN RESULTS: Both cause
      specific and all cause mortality increased with systolic blood pressure within
      each category of body mass index. Stroke mortality was not significantly
      associated with body mass index when adjusted for systolic blood pressure in
      either age group of men or women. Coronary heart disease mortality increased on
      average 30% per 5 kg/m2 increase in body mass index in men and women aged 30-59
      years at baseline. Adjusted for systolic blood pressure, the relative risks were
      reduced to 1.20 (95% confidence interval (CI) 1.12, 1.29) in men and 1.10 (95% CI
      1.03, 1.18) in women. They were similar at each level of systolic blood pressure.
      For coronary heart disease mortality in men and women aged 60-79 years at
      measurement a negative interaction between body mass index and systolic blood
      pressure was suggested in the first five years. Excluding the first five years,
      adjusted relative risks per 5 kg/m2, were 1.05 (95% CI 0.96, 1.15) in men and
      1.11 (95% CI 1.04, 1.17) in women in the older age group. There was an upturn in
      cardiovascular mortality at low levels of body mass index in both age groups of
      women, but not in men. CONCLUSIONS: Hypertension is an important risk factor for
      cardiovascular and all cause mortality even in the obese. Body mass index is
      generally a weak predictor of cardiovascular mortality in this population. It is
      a stronger risk factor of coronary death in men when measured at a younger age.
      Thin people with hypertension are not at particularly high risk of death from
      coronary heart disease compared with their obese counterparts, except possibly in
      the first few years after measurement in the elderly. Being underweight is
      associated with increased risk of death from all cardiovascular causes in women,
      but not in men.

PMID- 7629462
TI  - Ischaemic heart disease mortality among men in Norway: reversal of urban-rural
      difference between 1966 and 1989.
AB  - OBJECTIVE: This study aimed to examine regional urban-rural differences in
      mortality from ischaemic heart disease, including sudden death of unknown cause
      (IHD/SUD) in Norway from 1966-89, for men and women aged 30-69 years. DESIGN:
      Analysis was based on vital statistics. Regional mortality rates were obtained by
      aggregating the 443 municipalities in Norway into urban, rural, and intermediate
      municipalities. SETTINGS AND SUBJECTS: Norway. RESULTS: In 1966-70 the age
      adjusted IHD/SUD mortality in the age group 30-69 years was higher in urban than
      in rural areas; for men by 31% (95% CI 27%, 36%) and for women by 28% (95% CI
      19%, 36%). In 1986-89 the IHD/SUD mortality for men showed a reversed urban-rural
      gradient: it was 8% (95% CI 2%, 13%) higher in rural than in urban areas. The
      mortality rates for women were equal for both these aggregates. For men the
      results indicate that IHD/SUD mortality peaked first in urban municipalities and
      then, but at a lower level, in rural areas. For women there was a substantial
      decline in IHD/SUD mortality between 1966 and 1989, but an actual peak could not
      be demonstrated in any of the three aggregates during the period. The decline in
      IHD/SUD mortality among women was steepest in urban municipalities and least
      noticeable in rural municipalities, but the decline tapered off towards the end
      of the study period. CONCLUSION: The results confirm a phase-shifted peak in
      IHD/SUD mortality, which began in towns and ended in rural areas, and provides
      clues to the main underlying factors in the IHD epidemic at the population level.

PMID- 7629463
TI  - Variation in reported prevalences of hypertension in The Netherlands: the impact
      of methodological variables.
AB  - STUDY OBJECTIVE: To estimate the prevalence of hypertension in The Netherlands
      and to quantify the influence of methodological variables on the reported
      prevalences. DESIGN: A pooled analysis was performed based on reported age
      specific prevalences of hypertension. A logistic model was used to estimate the
      probability of hypertension. MAIN RESULTS: The age standardised prevalence of
      hypertension varies more than fivefold between studies carried out in The
      Netherlands. The probability of having hypertension was lower if blood pressure
      was measured at more than one point in time (Odds ratio 0.44 (OR) (95% confidence
      interval (95% CI) 0.38, 0.51) for men and 0.47 (0.41, 0.54) for women, and if the
      study was carried out more recently (OR 0.92 (0.91, 0.93) per year). The
      probability was higher if the study was carried out in a general practice (OR
      1.14 (1.03, 1.27) for men and 1.52 (1.36, 1.69) for women). The inclusion of
      treated people as hypertensive yields contradictory results for men and women.
      CONCLUSIONS: The strong variation in prevalence is explained by methodology and
      by a period effect indicating a decrease of the prevalence of hypertension over
      time. Whether this decrease is true or caused by confounding due to unknown or
      unreported methodological variation over time is unknown. For future studies, a
      standardised method could reduce the influence of methodological variables and
      thereby the variation in reported prevalences.

PMID- 7629464
TI  - Avoidable mortality in Lithuania.
AB  - STUDY OBJECTIVE: The study aimed to analyse avoidable mortality in Lithuania as
      an index of the quality of health care and to assess trends in avoidable
      mortality from 1970-90. SETTING AND PARTICIPANTS: All deaths of Lithuanian
      residents aged between 0 and 64 years between 1970 and 1990 were analysed.
      MEASUREMENTS AND MAIN RESULTS: Twenty seven per cent of all deaths in this age
      group were avoidable. Avoidable deaths were grouped into preventable and
      treatable ones. Treatable causes of death accounted for 54%, and preventable, 46%
      of avoidable mortality. Time trends showed that general mortality and mortality
      from avoidable causes of death in this age group were almost stable between 1970
      and 1990. Mortality from treatable causes of death fell, while deaths from
      preventable causes increased. The results in the preventable group were greatly
      affected by deaths from malignant neoplasms of trachea, bronchus, and lungs.
      Differences were noted between the sexes in total mortality as well as in
      avoidable mortality. CONCLUSIONS: Avoidable causes of death are relatively common
      and, consequently, they are of practical importance for public health and studies
      of the health care quality in Lithuania. Reorganisation of health care is to be
      carried out and considerable emphasis will be placed on health education,
      promotion, and prevention, as primary prevention measures have not been effective
      thus far.

PMID- 7629465
TI  - Medically treated suicide attempts: a four year monitoring study of the
      epidemiology in The Netherlands.
AB  - OBJECTIVE: The incidence of medically treated attempted suicides was investigated
      in a defined area in the western part of The Netherlands, and demographic groups
      at risk were identified. DATA AND METHODS: Suicide attempts treated at general
      hospitals, psychiatric hospitals, and in general practice were monitored between
      1 January 1989 and 1 January 1993. Information on demographic characteristics of
      the subjects who attempted suicide and characteristics of the attempts was
      registered through a monitoring system and there was maximum coverage. Data on
      the general population in the catchment area were derived from national,
      regional, and municipal bureaux of statistics. RESULTS: The mean annual
      incidences of medically treated suicide attempts (events) were 95/100,000 for
      males and 155/100,000 for females. At risk groups for attempted suicide were the
      young (< 40 years); females; people who were divorced, unemployed, or disabled;
      or those who had low levels of education. CONCLUSIONS: Apart from general
      hospitals and psychiatric hospitals, 28% of all reported suicide attempts were
      reported exclusively by general practitioners, which supports the conclusion that
      they are an important source of information. There were indications that the
      number of medically treated suicide attempts in this area is stabilising.

PMID- 7629466
TI  - Psychiatric morbidity: a multilevel approach to regional variations in the UK.
AB  - STUDY OBJECTIVE: To establish whether regional variations in psychiatric
      morbidity in Britain constitute a distinctive geography of mental health arising
      from factors that are context-specific at area level or whether these variations
      are an artifact generated by sampling fluctuations and differing population
      compositions in areas. DESIGN: Multilevel modelling techniques were applied to
      data from the 1984-85 health and lifestyle survey. The outcome was the prevalence
      of psychiatric morbidity as recorded by the application of the general health
      questionnaire in this survey. SETTING: The analysis was undertaken simultaneously
      at the individual level, electoral ward level, and regional level for England,
      Wales, and Scotland. PARTICIPANTS: A total of 6572 adults were selected from the
      electoral register. MAIN RESULTS: Regional variations were detected in crude
      aggregate general health questionnaire scores but these were found to be the
      result of sampling fluctuations and varying regional population compositions
      rather than higher level contextual effects. There was certainly no evidence of a
      clear north-south distinction in psychiatric morbidity as was suggested by
      earlier work. In addition, the local neighbourhood did not seem to have any
      importance beyond the type of people who lived there. A number of individual
      characteristics was shown to be associated with mental wellbeing but a large
      degree of individual variation remained unexplained. CONCLUSIONS: In terms of low
      level psychiatric disturbance it seems that the characteristics of individuals
      have greater importance than the characteristics of areas, although the latter
      may still operate as important mediating factors. Multilevel modelling represents
      a robust statistical method of examining area variations in health outcomes and
      further work needs to be conducted, particularly on more serious psychiatric
      conditions.

PMID- 7629467
TI  - Atopy: a predisposing factor for chronic bronchitis in Finland.
AB  - STUDY OBJECTIVE: To investigate the predictive value of atopy, smoking, and
      living in a farm environment in the development of chronic bronchitis. DESIGN:
      This was a cross sectional and longitudinal study. SETTING: Postal surveys
      carried out in Finland in 1975 and 1981. PARTICIPANTS: The study was part of the
      Finnish twin cohort study, which included adult twin pairs born in Finland before
      1958. The cross sectional sample consisted of 18,351 subjects, including 1025
      prevalent cases, and the follow up sample comprised 17,134 subjects, 553 of whom
      were incident cases of chronic bronchitis. MAIN RESULTS: According to the cross
      sectional data, chronic bronchitis was associated with atopy (relative risk 1.41)
      and smoking (2.43). In the follow up data, chronic bronchitis was related to
      atopy (1.28), smoking (2.31), and farming (1.45). CONCLUSIONS: The results
      confirm the earlier finding in the Finnish farming population that, in addition
      to smoking, atopy predisposes the development of chronic bronchitis. A farm
      environment was also found to be a predisposing factor. The results give further
      support to the "Dutch hypothesis" on the etiology of chronic bronchitis,
      according to which atopy is a predisposing factor.

PMID- 7629468
TI  - Physical activity, calcium intake, and bone mineral content in children in The
      Netherlands.
AB  - STUDY OBJECTIVE: To examine the relation between physical activity, calcium
      intake, and bone mineral content in children. DESIGN: Population based, cross
      sectional study. SETTING: Primary schools in Zoetermeer, The Netherlands.
      PARTICIPANTS: Altogether 1359 Dutch boys and girls, aged 7 to 11 years (response
      rate 88%). MEASUREMENTS: Bone mineral content was measured by quantitative
      roentgen microdensitometry of the midphalanx of the second digit at the
      diaphyseal and metaphyseal site. Maximal exercise testing, according to the Bruce
      treadmill protocol, was used to assess physical fitness. Habitual physical
      activity was assessed by use of a questionnaire on physical activities. Daily
      calcium intake from dairy products was estimated by use of a semiquantitative
      food frequency questionnaire. MAIN RESULTS: Bone mineral content in boys was not
      linearly associated with physical fitness after adjustments for differences in
      height, body weight, chronological age, and skeletal age. In girls a linear
      association was found at the metaphyseal site only. When extreme groups were
      compared, bone mineral content was found to be higher in "high fitness children"
      (upper decile) than "low fitness children" (lowest decile), with statistical
      significance reached in boys only. When analyses were performed in subgroups of
      skeletal age, a clear linear relation between physical fitness and bone mineral
      content was seen in the mature subgroup in both boys and girls. No linear
      association was found between habitual physical activity and bone mineral
      content, while the results in extreme groups (that is, upper versus lowest
      decile) and in subgroups of skeletal age were comparable to those on physical
      fitness in boys only. No association was found between daily calcium intake and
      bone mineral content in this age group. CONCLUSIONS: This cross sectional study
      in children aged 7 to 11 years suggests that an increased bone mineral content is
      found only in those with a high level of physical activity. This association is
      most pronounced in the more mature children. No evidence was found for an
      association between daily calcium intake and bone mineral content in childhood.

PMID- 7629469
TI  - Limb reduction defects in the northern region of England 1985-92.
AB  - STUDY OBJECTIVE: To test the hypothesis that children born to mothers living near
      the sea are at increased risk of limb reduction defects. DESIGN: Descriptive data
      analysis. SETTING: The northern health region of England. PATIENTS: All children
      born between 1 January 1985 and 31 December 1992 in the northern region of
      England with isolated limb reduction defects. MAIN RESULTS: The birth prevalence
      of isolated limb reduction defects was not affected by the distance the mother
      lived from the sea. There was some evidence of space-time clustering, but there
      was no evidence of statistically significant variation in the occurrence of the
      condition with sex, time of birth (monthly or yearly), or county of birth.
      CONCLUSIONS: There is no evidence that children born to mothers living near the
      sea are at increased risk of limb reduction defects.

PMID- 7629470
TI  - Prevalence of hepatitis B virus (HBV) infection in Singapore men with sexually
      transmitted diseases and HIV infection: role of sexual transmission in a city
      state with intermediate HBV endemicity.
AB  - STUDY OBJECTIVES: To describe the prevalence of hepatitis B virus (HBV) infection
      in patients with sexually transmitted diseases (STD) and human immunodeficiency
      virus (HIV) infection, and to determine the role of sexual transmission of HBV
      infection in Singapore. DESIGN: A cross sectional study of all consecutive men
      presenting with a new episode of STD at a government outpatient clinic and all
      men with HIV infection on routine follow up at a government hospital. The
      prevalence of various HBV markers was compared with that of healthy males aged 15
      years and above (controls). SETTING: Singapore, a city state of intermediate HBV
      endemicity. SUBJECTS: These comprised 497 STD patients, 47 HIV infected patients,
      and 418 controls. MAIN RESULTS: The overall seroprevalences of HBV infection in
      STD patients, HIV infected patients, and control subjects were 41.2%, 61.7%, and
      33.3%, respectively (p < 0.001). The seroprevalences of hepatitis B surface
      antigen (6.2%, 8.5%, and 4.5%, respectively) were comparable in the three groups.
      Using stepwise logistic regression analysis, the adjusted seroprevalences of HBV
      infection in STD and HIV infected patients were respectively 2.4 times (95%
      confidence interval (CI), 1.7, 3.3) and 3.3 times (95% CI 1.7, 6.3) higher than
      in controls. HBV infection rates were higher among Chinese (odds ratio (OR), 1.9;
      95% CI 1.6, 3.4) than non-Chinese, and among those aged 25-34 years (OR 2.4; 95%
      CI 1.6, 3.4), 35-44 years (OR 3.9; 95% CI 2.5, 5.9), and 45+ years (OR 6.2; 95%
      CI 3.8, 10.2) than in those aged 15-24 years. Sex related factors significantly
      associated with higher infection rates, independent of age and ethnic group, were
      reactive VDRL test (OR 2.4; 95% CI 1.2, 4.7), participation in anal intercourse
      (OR 2.3; 95% CI 1.2, 4.3), and having 10 or more lifetime sexual partners (OR
      1.5; 95% CI, 1.0, 2.1). CONCLUSION: The importance of sexual transmission of HBV
      in an area of intermediate HBV endemicity was confirmed. Patients attending STD
      clinics should be routinely screened for HBV markers and those found to be
      seronegative should be strongly advised to be immunised against this virus.

PMID- 7629471
TI  - A time to pregnancy questionnaire designed for long term recall: validity in
      Oxford, England.
AB  - STUDY OBJECTIVE: To establish the degree of validity of data on time to
      pregnancy, derived retrospectively using a short questionnaire. DESIGN:
      Information from the questionnaire was compared with data that had been collected
      concurrently from the same individuals. SETTING AND PARTICIPANTS: Questionnaires
      were mailed to 1647 women who continue to be followed up by the Oxford Family
      Planning Association contraceptive study, and a further 424 were approached for
      personal interview. Response rates were 91% and 79% respectively. MAIN RESULTS:
      Matching was successful in 91% of pregnancies. Median recall time was 14 years
      (interquartile range, 11-16 years). At the group level, remarkably good agreement
      was found between the two sources of information, presented as cumulative
      percentage distributions of live births. The findings were at least as good with
      longer recall (> 14 years) as with shorter recall. Digit performance was present
      to a limited degree. At the individual level, some misclassification was evident,
      which has implications for statistical power. For detection of clinical
      infertility (no conception within 12 months), the sensitivity was in the range
      67%-91%, and the specificity was 92%-96%. Variations with format, duration of
      recall, age at delivery, year of birth, parity, social class, smoking habit, last
      contraceptive method, and outcome (live birth or not) were generally small, and
      were not statistically significant. CONCLUSIONS: Time to pregnancy is a sensitive
      way of assessing reproductive function in either sex. Valid data at a group level
      can be derived retrospectively, with a long duration of recall, using a short
      questionnaire.

PMID- 7629472
TI  - Potential years of life lost: what is the denominator?
AB  - OBJECTIVE: To suggest an appropriate denominator for use with the statistic
      "potential years of life lost", in order to facilitate valid comparisons between
      health authorities. DESIGN: Analysis of OPCS population and mortality data for
      the period 1987-91. SETTING: Data for Wales were analysed to provide comparisons
      between the nine district health authorities. SUBJECTS: There were 46,139 males
      and 30,258 females--that is, all deaths of Welsh residents, aged under 75 years,
      during the period 1987-91. MAIN RESULTS: The use of age sensitive denominators
      with the potential years of life lost statistic alters the rank position of Welsh
      district health authorities. CONCLUSION: It is suggested that potential years of
      life lost should be expressed as a rate per 100,000 potential years of life in
      public health common data sets, and elsewhere, to facilitate valid comparisons
      between health authorities.

PMID- 7629473
TI  - Alzheimer's disease and the relationship between silicon and aluminium in water
      supplies in northern England.

PMID- 7629474
TI  - Asthma history and sociodemographic characteristics in elderly French people.

PMID- 7629475
TI  - Prevalence of asthma and related factors in primary school children in an
      industrial part of England.

PMID- 7629476
TI  - Social network and lifestyle in Danish adults.

PMID- 7629477
TI  - Health expectancy: an indicator for change?

PMID- 7629478
TI  - Socioeconomic factors and injuries.

PMID- 7629479
TI  - Future challenges to coronary angioplasty: perspectives on intracoronary imaging
      and physiology.
AB  - Several intravascular techniques have been developed with the purpose of
      achieving optimal guidance for treatment during coronary angioplasty (PTCA).
      Although the coronary angiographic technique is well established, there are still
      some inherent limitations. Due to intimal rupture, tears, dissection and thrombus
      following PTCA treatment, angiography does not allow exact delineation of the
      true borders of the vessel. Coronary angioscopy is currently the most sensitive
      method to detect coronary thrombus and can also be used to classify atheromatous
      plaques. Furthermore, coronary dissection can be detected with more accuracy than
      with angiography. One limitation associated with angioscopy is the need to
      occlude the vessel during imaging, which may create myocardial ischaemia.
      Furthermore, there is presently no method for quantifying angioscopic findings.
      Intravascular ultrasound produces a cross-sectional image of the vessel, which
      permits analysis of the layers of the vascular wall. Characterization and
      classification of various types of plaque can be made because thrombus, lipid,
      fibrous tissue and calcium have different ultrasonic echogenicity. Flow velocity
      measurement with the Doppler technique is an interesting approach to the
      physiological assessment of coronary stenoses. Coronary flow reserve can be
      estimated with this method and monitoring of the flow signal following
      angioplasty will aid in the diagnosis of flow-limiting complications. The trans
      stenotic pressure gradient is a valuable measure of the haemodynamic importance
      of a coronary lesion. Trans-stenotic gradients during maximal hyperaemia obtained
      with a miniaturized pressure transducer yield reliable information regarding the
      severity of the stenosis, and the pressure values may be used to calculate the
      relative coronary flow reserve. In conclusion, all of these intracoronary
      diagnostic techniques will to some extent play a role in the future of coronary
      angioplasty. Safety, cost and complexity are some of the factors which will
      determine the growth potential of each method.

PMID- 7629480
TI  - Intraplaque haemorrhage at carotid artery surgery--a predictor of cardiovascular
      mortality.
AB  - OBJECTIVE: To ascertain whether carotid intraplaque haemorrhage (IH) in patients
      undergoing carotid artery surgery is a predictor of increased cardiac mortality
      over a 5.5 year follow-up. DESIGN AND SUBJECTS: Carotid artery plaques were
      obtained at surgery from 47 consecutive patients (41 men, six women), median age
      67 (range 48-81) years, with symptoms of carotid transient ischaemic attacks
      (TIAs) or carotid territory minor stroke. As determined at preoperative
      angiography, the degree of stenosis was 50-99%. Specimens were classified
      histologically as manifesting severe atherosclerosis, fibrous plaque, IH, or
      residual IH debris. SETTING: Medical Angiology and Vascular Surgery Units, Malmo
      General Hospital. INTERVENTION: Carotid endarterectomy. MAIN OUTCOME MEASURE:
      Correlation between mortality and IH. RESULTS: At follow-up after 5.5 years,
      mortality was 28% (13/47) overall, 92% (12/13) in the IH subgroup [of stroke (n =
      1) or myocardial infarction (n = 11)], but only 3% (1/34), of pancreatic cancer,
      in the non-IH subgroup (P = 0.0001). Mortality was also significantly higher in
      the severe atherosclerosis than in the fibrous plaque subgroup, 39% (12/31) vs.
      6% (1/16) (P = 0.044), but not significantly increased in any other subgroup
      (fibrous plaque, residual IH, TIA, minor stroke, or acetylsalicylic acid or
      anticoagulant treatment). No correlation existed between IH or death and
      haemoglobin value or platelet count. CONCLUSIONS: Evidence of recent IH seen at
      carotid artery surgery may be a marker of cardiovascular mortality. As IH was
      also found in a post-mortem control subgroup, the difference may be due to
      abnormality in blood components (e.g., coagulation factors) or impaired vessel
      wall healing capacity (e.g. endothelial dysfunction).

PMID- 7629481
TI  - Lecithin-cholesterol acyltransferase deficiency presenting with acute
      pancreatitis: effect of infusion of normal plasma on triglyceride-rich
      lipoproteins.
AB  - A 38-year-old Asian man presented with acute pancreatitis, marked
      hypertriglyceridaemia and macroproteinuria, 20 years after the diagnosis of
      lecithin-cholesterol acyltransferase (LCAT) deficiency. After recovery, he
      exhibited macroproteinuria and chylomicronaemia despite treatment with a very-low
      fat diet. Infusion of normal plasma significantly increased the proportion of
      cholesterol esters in the patient's plasma and significantly lowered chylomicron
      triglyceride levels, but not proteinuria. We conclude that renal dysfunction may
      be a late manifestation of LCAT deficiency and that it may lead to severe
      chylomicronaemia and acute pancreatitis. Infusion of normal plasma corrects the
      dyslipidaemia in LCAT deficiency, but in the short term does not improve renal
      function.

PMID- 7629482
TI  - Circulating autoantibodies as serological markers in the differential diagnosis
      of pulmonary renal syndrome.
AB  - OBJECTIVES: Pulmonary renal syndrome (lung haemorrhage and glomerulonephritis) is
      a fulminant condition that warrants a rapid diagnosis and treatment to prevent
      mortality and preserve renal functions. However, the patients frequently present
      with non-specific pulmonary symptoms in the early phase of the syndrome and the
      diagnosis is often missed. Recently, several autoantibodies have been described
      in association with various forms of glomerulonephritis. We evaluated the
      association as well as the diagnostic and the prognostic significance of these
      antibodies in pulmonary renal syndrome. DESIGN: Retrospective clinical study.
      SETTING: University Hospital. SUBJECTS: Forty consecutive patients with biopsy
      verified glomerulonephritis and overt haemoptysis or pulmonary infiltrates
      compatible with lung haemorrhage. INTERVENTIONS: Analysis of proteinase 3
      antineutrophil cytoplasm antibodies (PR3-ANCA), myeloperoxidase (MPO)-ANCA,
      antiglomerular basement membrane (GBM) and anti-entactin antibodies. RESULTS:
      Thirty-six (90%) patients possessed one or more autoantibodies. Twenty-seven
      (70%) patients had ANCA (PR3-ANCA, MPO-ANCA or both). The remaining positive
      patients (n = 9) had anti-GBM antibodies. Only two patients had anti-entactin
      antibodies, suggesting a poor association of these antibodies with PRS. The
      majority of patients with anti-GBM antibodies had a very poor clinical outcome
      (five irreversible renal failure; three deaths). On the other hand, despite no
      significant difference in clinical features or renal morphology from patients
      with anti-GBM antibodies, 19 patients (70%) with ANCA recovered completely
      following treatment. CONCLUSIONS: Our study demonstrated that the presence of
      autoantibodies is a predominant feature of PRS and that the type of immunologic
      injury is of paramount importance in determining the course of illness in this
      syndrome. Analysis of the aforementioned antibodies can help in an early
      differential diagnosis and thus, in better management of PRS.

PMID- 7629483
TI  - Clinical and virological findings in mixed cryoglobulinaemia.
AB  - OBJECTIVES: As a close relationship has been established between mixed
      cryoglobulinaemia and hepatitis C virus (HCV) infection, the clinical,
      histological and virological findings of patients affected by mixed
      cryoglobulinaemia were determined. DESIGN: Hepatitis C virus infection was
      investigated by the presence of anti-HCV antibodies and PCR amplification of the
      5' untranslated region (5' UTR), and the genotype of HCV was also determined
      according to Okamoto. A bone marrow biopsy was performed in all patients and
      liver and kidney biopsies when indicated. SUBJECTS: Eighty-two subjects affected
      by mixed cryoglobulinaemia were enrolled in this study. RESULTS: The prevalence
      of anti-HCV antibodies was high (83%); PCR amplification of the 5'UTR region was
      performed in 52 subjects and in 44 of them (85%) the results were positive. In
      the same subjects, the Core region amplification was positive in 46 cases (88%).
      A high prevalence of genotype II was found (54%). Chronic liver disease was
      present in 55 patients (67%). Bone marrow biopsies showed the presence of low
      grade non-Hodgkin's lymphomas in 11 cases (13%). Membrano-proliferative
      glomerulonephritis was found in seven subjects (8%). CONCLUSIONS: Mixed
      cryoglobulinaemia is associated with HCV infection in the nearly all cases.
      Several HCV genotypes are involved in the pathogenesis of this disease. Mixed
      cryoglobulinaemia is associated with a high prevalence of chronic liver disease,
      low-grade non-Hodgkin's lymphomas and membrano-proliferative glomerulonephritis.

PMID- 7629484
TI  - Short-term treatment of Graves' disease with methimazole in high versus low
      doses.
AB  - OBJECTIVES: To compare the relapse rates in Graves' disease the first 2 years
      after methimazole 60 mg day-1 combined with thyroxine versus a titration regimen
      with methimazole alone, and to look for possible prognostic factors. DESIGN: A
      randomized, open, prospective study. Methimazole was given for 6 months in both
      groups, and thyroid status evaluated every 3rd month during the first year, and
      every 6th month during the second year. SETTING: The study was performed at our
      outpatient clinic with patients referred from primary care. SUBJECTS: Fifty-six
      patients were included. One became pregnant and one dropped out during the
      treatment period. Furthermore, nine patients in the high-dose and four in the low
      dose group stopped the treatment because of side-effects. Thus, 19 patients in
      the high- and 22 in the low-dose group completed 6 months with methimazole.
      RESULTS: In those tolerating the treatment, the relapse rates in the high- and
      low-dose groups were 26.3 vs. 59.1% (P < 0.05), 42.1 vs. 77.3% (P < 0.02); and
      57.9 vs. 77.3% (NS) after 3, 12 and 24 months, respectively. The corresponding
      relapse rates calculated on an 'intention to treat' basis were: 51.7 vs. 66.7%;
      62.1 vs. 81.5%: 72.4 vs. 81.5% (NS). The thyroid volume was significantly (P <
      0.05) larger in those that relapsed (17.8 +/- 2.9 vs. 11.6 +/- 1.2 mL; mean +/-
      SEM). CONCLUSIONS: In those tolerating the treatment, methimazole significantly
      reduced the relapse rate the 1st year when given in a high dose. However, the
      relapse rates in both groups, and the number of side-effects in the high-dose
      group, were unacceptably high.

PMID- 7629485
TI  - Disturbed energy balance in skeletal muscle of patients with untreated primary
      hypertension.
AB  - OBJECTIVE: It has been shown that the distribution of Na+ and Ca2+ in various
      cells is abnormal in patients with untreated primary hypertension, indicating an
      altered membrane permeability in these cells. This would activate certain ion
      pumps and thereby enhance ATP turnover. We investigated possible alterations in
      energy economy of skeletal muscle tissue. DESIGN: Skeletal muscle energetics were
      studied in vitro and in vivo in patients with untreated primary hypertension.
      Phosphocreatine (PCr), energy charge (EC) and total adenylate values were
      assessed. SETTING: The study was performed at the outpatient clinic of a general
      hospital and at a university clinical chemistry department and at a specialized
      bioenergetic laboratory. SUBJECTS: Altogether, 17 patients with untreated primary
      hypertension were examined together with matched, healthy and normotensive
      controls with normal body-mass index. MAIN OUTCOME MEASURES: Skeletal muscle
      biopsies were obtained from 10 patients and 10 controls for analysis of high
      energy phosphate compounds. Another seven patients were enrolled for in vivo NMR
      spectroscopy. RESULTS: We found a decrease of 30% (P < 0.01) of PCr content in
      the patients, whilst EC and total adenylates were unchanged. Nuclear magnetic
      resonance spectroscopy showed an abnormal decrease of PCr during exercise
      followed by a markedly slower regeneration of PCr during post-exercise recovery
      parallelled by a slower recovery of pH. This phenomenon was mirrored by a more
      pronounced decrease of ATP/Pi in patients during exercise and a slower recovery
      of ATP/Pi. CONCLUSION: The data are compatible with an increased ATP turnover in
      skeletal muscle cells of patients with untreated primary hypertension although
      ATP was favoured and kept at a normal resting level at the expense of the PCr
      store.

PMID- 7629486
TI  - Primary antiphospholipid syndrome associated with postoperative primary adrenal
      failure.
AB  - A 51-year-old Caucasian male without previous history of thromboembolic disease
      developed Coomb's positive haemolytic anaemia, thrombocytopenia, transient
      paranoid psychosis and bilateral adrenal haemorrhage with primary adrenal failure
      after surgery for inguinal hernia. The activated partial thromboplastin time was
      spontaneously prolonged, and lupus anticoagulant and anticardiolipin antibodies
      were detected. In the absence of criteria for classification of systemic lupus
      erythematosus (SLE), the entity was classified as a primary antiphospholipid
      syndrome. Despite the persistence of the serological abnormalities, the patient
      remains well after substitution with cortisone. Primary adrenal failure due to
      adrenal haemorrhage can be associated with the primary antiphospholipid syndrome.

PMID- 7629487
TI  - Angio-oedema induced by enalapril.
AB  - We report the case of a patient who, 9 months after initiation of enalapril and
      hydrochlorothiazide combination treatment for hypertension, developed angio
      oedema with near fatal outcome. Our patient was successfully intubated using a
      flexible bronchofiberoscope. This case demonstrates that patients given an
      angiotensin-converting enzyme (ACE) inhibitor may develop serious facial and
      laryngeal swelling even several months after the initiation of treatment. The
      occurrence of even mild swelling should lead to prompt cessation of the drug.
      Patients with incipient ACE inhibitor-related angio-oedema should, without any
      delay, be referred to hospital for emergency treatment.

PMID- 7629488
TI  - Idiopathic CD4+ T-lymphocytopenia with opportunistic infection and non-Hodgkin's
      lymphoma.

PMID- 7629489
TI  - Refractory oedema in congestive heart failure: a contributory role of loop
      diuretics.

PMID- 7629491
TI  - Metabolic and atherogenic effects of trans fatty acids.

PMID- 7629490
TI  - Absence of circulating antineutrophil cytoplasmic antibodies in familial
      Mediterranean fever.

PMID- 7629492
TI  - Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) in malignant
      disease.
AB  - The first clinical case of a patient with the syndrome of inappropriate secretion
      of antidiuretic hormone (SIADH) was presented by Schwartz et al. in 1957 (Am J
      Med 1957; 23: 529-42), describing two patients with lung cancer who developed
      hyponatraemia associated with continued urinary sodium loss. They postulated that
      the tumours led to the inappropriate release of antidiuretic hormone (ADH), later
      discovered to consist of arginine-vasopressin (AVP). This suggestion was later
      confirmed in several studies. The clinical description of the syndrome has
      changed little since the original observation, and the cardinal findings of SIADH
      are as follows: (i) hyponatraemia with corresponding hypo-osmolality of the serum
      and extracellular fluid, (ii) continued renal excretion of sodium. (iii) absence
      of clinical evidence of fluid volume depletion, (iv) osmolality of the urine
      greater than that appropriate for the concomitant osmolality of the plasma, i.e.
      urine less than maximal diluted, and (v) normal function of kidneys, suprarenal
      glands and thyroid glands. Measurement of AVP in plasma is not a part of the
      definition of SIADH. SIADH may be caused by a variety of malignant tumours, but
      may also be caused by various other conditions, such as disorders involving the
      central nervous system, intrathoratic disorders such as infections, positive
      pressure ventilation and conditions with decrease in left atrial pressure. Also,
      a large number of pharmaceutical agents have been shown to produce SIADH,
      including a number of cytotoxic drugs such as vincristine, vinblastine,
      cisplatin, cyclophosphamide, and melphalan. A broad spectrum of malignant tumours
      has been reported to cause SIADH; however, most of these observations have been
      in case reports including very few patients. This includes a number of primary
      brain tumours, haematologic malignancies, intrathoracic non-pulmonary cancers,
      skin tumours, gastrointestinal cancers, gynaecological cancer, breast-and
      prostatic cancer, and sarcomas. Larger series of patients have revealed that
      SIADH occurs in 3% of patients with head and neck cancer (47 cases out of 1696
      patients), in 0.7% of patients with non-small-cell lung cancer (three cases out
      of 427 patients), and in 15% of cases of small-cell lung cancer (214 cases out of
      1473 patients). The optimal therapy for SIADH is to treat the underlying
      malignant disease. If this is not possible, or if the disease has become
      refractory, other treatment methods are available such as water restriction,
      demeclocycline therapy, or, in severe cases, infusion of hypertonic saline
      together with furosemide during careful monitoring.

PMID- 7629493
TI  - Hybrid resistance and the Ly-49 family of natural killer cell receptors.

PMID- 7629494
TI  - The endocytic activity of dendritic cells.

PMID- 7629495
TI  - Cloning and functional characteristics of murine large granular lymphocyte-1: a
      member of the Ly-49 gene family (Ly-49G2)
AB  - Large granular lymphocyte (LGL) 1 is a cell surface glycoprotein expressed on a
      subset (50%) of C57BL/6 natural killer (NK) cells. Immunoprecipitation
      experiments reveal that the LGL-1 protein exists as a disulfide-linked 40-kD
      homodimer. Functional studies of LGL-1+ cells indicate that selected H-2d target
      cells are not lysed efficiently by these interleukin (IL)-2-cultured NK cells.
      These findings suggested that LGL-1 may be a member of the Ly-49 gene family.
      Here we report the molecular cloning of the LGL-1 cDNA from a severe combined
      immunodeficient-adherent lymphokine-activated killer cell library transfected
      into Cos-7 cells and find LGL-1 to be homologous to the Ly-49 gene at both the
      nucleotide (85%) and amino acid levels (73%). Sequencing of our LGL-1 cDNA has
      revealed it to be nearly identical to the Ly-49G2 cDNA recently isolated by cross
      hybridization with an Ly-49 probe. LGL-1 represents a type II transmembrane
      protein of 267 amino acids with its carboxyl end exposed extracellularly. The LGL
      1 protein contains 11 highly conserved cysteine residues and a 25-amino acid
      transmembrane region. Southern blot analysis demonstrates that there are a number
      of homologous genes in mouse DNA that hybridize strongly to LGL-1. Northern
      analyses using poly A+ RNA from LGL-1+ NK cells indicate that LGL-1 is expressed
      as a 1.4 kb mRNA. Two-color flow cytometry analysis (FCA) of C57BL/6 splenic NK
      cells demonstrates that LGL-1 and Ly-49 label overlapping subsets of cells. FCA
      identifies four subsets of NK cells as defined by LGL-1 versus Ly-49 staining. We
      have sorted these individual subsets, expanded them in IL-2, and performed
      cytotoxicity experiments to determine their target cell profiles in relation to
      class I expression. Results of these studies are complex, but indicate that Ly-49
      may not be the only molecule that recognizes class I as an inhibitory signal for
      cytotoxicity. LGL-1+ cells also fail to lyse several H-2d-expressing tumor
      targets and concanavalin A lymphoblasts from BALB/c but not C57BL/6 mice. This
      inhibition of lysis by LGL-1+ NK cells is negated by addition of monoclonal
      antibody (mAb) 4D11 that recognizes the LGL-1 protein. When mAbs to the class I
      molecules H-2Dd and H-2Ld (alpha 1 alpha 2 domains only) are added to
      cytotoxicity assays, LGL-1+ cells lyse H-2d targets very effectively.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7629496
TI  - Cloning and characterization of 5E6(Ly-49C), a receptor molecule expressed on a
      subset of murine natural killer cells.
AB  - 5E6 is a cell surface molecule expressed on a subpopulation of murine natural
      killer (NK) cells that are involved in the specific rejection of H-2d or H-2f
      (hemopoietic histocompatibility determinant 2) bone marrow cell grafts. Here, we
      isolated and cloned the gene encoding 5E6 and determined the nucleotide sequence
      of the cDNA. 5E6 is nearly identical to Ly-49C; the deduced amino acid sequence
      reveals a polypeptide of 266 amino acids with a molecular weight of 31,284 that
      contains multiple cysteine residues to explain its disulfide-linked homodimer
      structure and five potential N-linked glycosylation sites. 5E6 is a type II
      integral membrane protein with an extracellular carbohydrate recognition domain
      characteristic of C-type (Ca(2+)-dependent) animal lectins. Chromosomal mapping
      indicates that 5E6 is located within the NK gene complex on chromosome 6. The
      sequence of 5E6 mRNA and the degree of glycosylation of 5E6 protein are under
      genetic control. Immunoprecipitation before removal of N-linked sugars reveals
      different size molecules. There are several nucleotide differences among BALB/c,
      B6, and NZB mRNAs; however, none of them would be expected to affect N
      glycosylation. Of particular interest are two findings: (a) BALB/c, B6, and
      (BALB/c x B6)F1 5E6 reduced molecules are approximately 65, 54, and 54 kD, and
      (b) the cDNA sequence of (BALB/c x B6)F1 is identical to B6. Thus, there appears
      to be allelic exclusion of 5E6 expression that may be related to the ability of
      F1 hybrid mice to reject parental H-2d bone marrow cell grafts.

PMID- 7629497
TI  - Major histocompatibility complex class II compartments in human B lymphoblastoid
      cells are distinct from early endosomes.
AB  - In human B lymphoblastoid cell lines, the majority of major histocompatibility
      complex (MHC) class II heterodimers are located on the cell surface and in
      endocytic compartments, while invariant chain (Ii)-associated class II molecules
      represent biosynthetic intermediates which are present mostly in the endoplasmic
      reticulum and Golgi complex. To investigate the origin of the MHC class II
      positive compartments and their relation to early endosomes, the intracellular
      distribution of MHC class II molecules and Ii in relation to endocytic tracers
      was studied in human lymphoblastoid B cells by immunoelectronmicroscopy on
      ultrathin cryosections. Cross-linking of surface immunoglobulins, followed by a
      brief period of internalization of the immune complexes, did not alter the
      intracellular distribution of MHC class II molecules. While early endosomes were
      abundantly labeled for the cross-linked immunoglobulins, < 1% of total MHC class
      II molecules were detectable in early endosomes. MHC class II- and Ii-positive
      structures associated with the trans-Golgi network can be reached by endocytosed
      bovine serum albumin (BSA)-gold conjugates after 30 min of internalization.
      Prolonged exposure to BSA-gold allowed visualization of later endocytic
      compartments, in which a progressive loss of Ii was observed: first the lumenal
      portion, and then the cytoplasmic portion of Ii escaped detection, culminating in
      the formation of MHC class II-positive compartments (MIIC) devoid of Ii. The loss
      of Ii also correlated with a transition from a multivesicular to a multilaminar,
      electron-dense MIIC. The intracellular compartments in which class II molecules
      reside (MIIC) are therefore a heterogeneous set of structures, part of the later
      aspects of the endocytic pathway.

PMID- 7629499
TI  - Sequential reduction of mitochondrial transmembrane potential and generation of
      reactive oxygen species in early programmed cell death.
AB  - Programmed cell death (PCD) is a physiological process commonly defined by
      alterations in nuclear morphology (apoptosis) and/or characteristic stepwise
      degradation of chromosomal DNA occurring before cytolysis. However, determined
      characteristics of PCD such as loss in mitochondrial reductase activity or
      cytolysis can be induced in enucleated cells, indicating cytoplasmic PCD control.
      Here we report a sequential disregulation of mitochondrial function that precedes
      cell shrinkage and nuclear fragmentation. A first cyclosporin A-inhibitable step
      of ongoing PCD is characterized by a reduction of mitochondrial transmembrane
      potential, as determined by specific fluorochromes (5,5',6,6'-tetrachloro
      1,1',3,3'-tetraethylbenzimidazolcarbocyanine++ + iodide;
      3,3'dihexyloxacarbocyanine iodide). Cytofluorometrically purified cells with
      reduced mitochondrial transmembrane potential are initially incapable of
      oxidizing hydroethidine (HE) into ethidium. Upon short-term in vitro culture,
      such cells acquire the capacity of HE oxidation, thus revealing a second step of
      PCD marked by mitochondrial generation of reactive oxygen species (ROS). This
      step can be selectively inhibited by rotenone and ruthenium red yet is not
      affected by cyclosporin A. Finally, cells reduce their volume, a step that is
      delayed by radical scavengers, indicating the implication of ROS in the apoptotic
      process. This sequence of alterations accompanying early PCD is found in very
      different models of apoptosis induction: glucocorticoid-induced death of
      lymphocytes, activation-induced PCD of T cell hybridomas, and tumor necrosis
      factor-induced death of U937 cells. Transfection with the antiapoptotic
      protooncogene Bcl-2 simultaneously inhibits mitochondrial alterations and
      apoptotic cell death triggered by steroids or ceramide. In vivo injection of
      fluorochromes such as 5,5',6,6'-tetrachloro-1,1',3,3'
      tetraethylbenzimidazolcarbocyanine iodide; 3,3'dihexyloxacarbocyanine iodide; or
      HE allows for the detection of cells that are programmed for death but still lack
      nuclear DNA fragmentation. In particular, assessment of mitochondrial ROS
      generation provides an accurate picture of PCD-mediated lymphocyte depletion. In
      conclusion, alterations of mitochondrial function constitute an important feature
      of early PCD.

PMID- 7629498
TI  - The alpha 4 integrin chain is a ligand for alpha 4 beta 7 and alpha 4 beta 1.
AB  - The heterodimeric alpha 4 integrins alpha 4 beta 7 lymphocyte Peyer's patch
      adhesion molecule ([LPAM]-1) and alpha 4 beta 1 (very late antigen-4) are cell
      surface adhesion molecules involved in lymphocyte trafficking and lymphocyte-cell
      and matrix interactions. Known cellular ligands include vascular cell adhesion
      molecule (VCAM)-1, which binds to alpha 4 beta 1 and alpha 4 beta 7, and the
      mucosal addressin cell adhesion molecule (MAdCAM)-1, which binds to alpha 4 beta
      7. Here we show that the alpha 4 chain of these integrins can itself serve as a
      ligand. The alpha 4 chain, immunoaffinity purified and immobilized on glass
      slides, binds thymocytes and T lymphocytes. Binding exhibits divalent cation
      requirements and temperature sensitivity which are characteristic of integrin
      mediated interactions, and is specifically inhibited by anti-alpha 4 integrin
      antibodies, which exert their effect at the cell surface. Cells expressing
      exclusively alpha 4 beta 7 (TK-1) or alpha 4 beta 1 (L1-2) both bound avidly,
      whereas alpha 4-negative cells did not. A soluble 34-kD alpha 4 chain fragment
      retained binding activity, and it inhibited lymphocyte adhesion to alpha 4
      ligands. It has been shown that alpha 4 integrin binding to fibronectin involves
      an leucine-aspartic acid-valine (LDV) motif in the HepII/IIICS region of
      fibronectin (CS-1 peptide), and homologous sequences are important in binding to
      VCAM-1 and MAdCAM-1. Three conserved LDV motifs occur in the extracellular
      sequence of alpha 4. A synthetic LDV-containing alpha 4-derived oligopeptide
      supports alpha 4-integrin-dependent lymphocyte adhesion and blocks binding to the
      34-kD alpha 4 chain fragment. Our results suggest that alpha 4 beta 7 and alpha 4
      beta 1 integrins may be able to bind to the alpha 4 subunit on adjacent cells,
      providing a novel mechanism for alpha 4 integrin-mediated and activation
      regulated lymphocyte interactions during immune responses.

PMID- 7629500
TI  - Growth of donor-derived dendritic cells from the bone marrow of murine liver
      allograft recipients in response to granulocyte/macrophage colony-stimulating
      factor.
AB  - Allografts of the liver, which has a comparatively heavy leukocyte content
      compared with other vascularized organs, are accepted permanently across major
      histocompatibility complex barriers in many murine strain combinations without
      immunosuppressive therapy. It has been postulated that this inherent
      tolerogenicity of the liver may be a consequence of the migration and
      perpetuation within host lymphoid tissues of potentially tolerogenic donor
      derived ("chimeric") leukocytes, in particular, the precursors of chimeric
      dendritic cells (DC). In this study, we have used granulocyte/macrophage colony
      stimulating factor to induce the propagation of progenitors that give rise to DC
      (CD45+, CD11c+, 33D1+, nonlymphoid dendritic cell 145+, major histocompatibility
      complex class II+, B7-1+) in liquid cultures of murine bone marrow cells. Using
      this technique, together with immunocytochemical and molecular methods, we show
      that, in addition to cells expressing female host (C3H) phenotype (H-2Kk+; I-E+;
      Y chromosome-), a minor population of male donor (B10)-derived cells (H-2Kb+; I
      A+; Y chromosome+) can also be grown in 10-d DC cultures from the bone marrow of
      liver allograft recipients 14 d after transplant. Highly purified nonlymphoid
      dendritic cell 145+ DC sorted from these bone marrow-derived cell cultures were
      shown to comprise approximately 1-10% cells of donor origin (Y chromosome+) by
      polymerase chain reaction analysis. In addition, sorted DC stimulated naive,
      recipient strain T lymphocytes in primary mixed leukocyte cultures. Evidence was
      also obtained for the growth of donor-derived cells from the spleen but not the
      thymus. In contrast, donor cells could not be propagated from the bone marrow or
      other lymphoid tissues of nonimmunosuppressed C3H mice rejecting cardiac
      allografts from the same donor strain (B10). These findings provide a basis for
      the establishment and perpetuation of cell chimerism after organ transplantation.

PMID- 7629501
TI  - Dendritic cells use macropinocytosis and the mannose receptor to concentrate
      macromolecules in the major histocompatibility complex class II compartment:
      downregulation by cytokines and bacterial products.
AB  - We have previously demonstrated that human peripheral blood low density
      mononuclear cells cultured in granulocyte/macrophage colony-stimulating factor
      (GM-CSF) and interleukin (IL)-4 develop into dendritic cells (DCs) that are
      extremely efficient in presenting soluble antigens to T cells. To identify the
      mechanisms responsible for efficient antigen capture, we studied the endocytic
      capacity of DCs using fluorescein isothiocyanate-dextran, horseradish peroxidase,
      and lucifer yellow. We found that DCs use two distinct mechanisms for antigen
      capture. The first is a high level of fluid phase uptake via macropinocytosis. In
      contrast to what has been found with other cell types, macropinocytosis in DCs is
      constitutive and allows continuous internalization of large volumes of fluid. The
      second mechanism of capture is mediated via the mannose receptor (MR), which is
      expressed at high levels on DCs. At low ligand concentrations, the MR can deliver
      a large number of ligands to the cell in successive rounds. Thus, while
      macropinocytosis endows DCs with a high capacity, nonsaturable mechanism for
      capture of any soluble antigen, the MR gives an extra capacity for antigen
      capture with some degree of selectivity for non-self molecules. In addition to
      their high endocytic capacity, DCs from GM-CSF + IL-4-dependent cultures are
      characterized by the presence of a large intracellular compartment that contains
      high levels of class II molecules, cathepsin D, and lysosomal-associated membrane
      protein-1, and is rapidly accessible to endocytic markers. We investigated
      whether the capacity of DCs to capture and process antigen could be modulated by
      exogenous stimuli. We found that DCs respond to tumor necrosis factor alpha, CD40
      ligand, IL-1, and lipopolysaccharide with a coordinate series of changes that
      include downregulation of macropinocytosis and Fc receptors, disappearance of the
      class II compartment, and upregulation of adhesion and costimulatory molecules.
      These changes occur within 1-2 d and are irreversible, since neither pinocytosis
      nor the class II compartment are recovered when the maturation-inducing stimulus
      is removed. The specificity of the MR and the capacity to respond to inflammatory
      stimuli maximize the capacity of DCs to present infectious non-self antigens to T
      cells.

PMID- 7629502
TI  - Induction of G1 arrest by down-regulation of cyclin D3 in T cell hybridomas.
AB  - The relationship between activation-induced growth inhibition and regulation of
      the cell cycle progression was investigated in T cell hybridomas by studying the
      function of the cell cycle-regulating genes such as G1 cyclins and their
      associated kinases. Activation of T cell hybridomas by anti-T cell receptor
      antibody induces growth arrest at G1 phase of the cell cycle and subsequently
      results in activation-driven cell death. Rapid reduction of both messenger RNA
      and protein level of the cyclin D3 is accompanied by growth arrest upon
      activation. Although the residual cyclin D3 protein forms a complex with cdk4
      protein, cyclin D3-dependent kinase activity is severely impaired. Stable
      transfectants engineered to express cyclin D3 override the growth arrest upon
      activation. These results imply that the activation signal through T cell
      receptor induces the down-regulation of cyclin D3 expression and cyclin D3
      dependent kinase activity, leading to growth arrest in G1 phase of the cell cycle
      in T cells.

PMID- 7629503
TI  - Mechanisms underlying the monocyte-mediated antibody-dependent killing of
      Plasmodium falciparum asexual blood stages.
AB  - The relevance of the antibody-dependent cellular inhibition (ADCI) of Plasmodium
      falciparum to clinical protection has been previously established by in vitro
      studies of material obtained during passive transfer of protection by
      immunoglobulin G in humans. We here report further in vitro investigations aimed
      at elucidating the mechanisms underlying this ADCI effect. Results obtained so
      far suggest that (a) merozoite uptake by monocytes (MN) as well as by
      polymorphonuclear cells has little influence on the course of parasitemia; (b)
      the ADCI effect is mediated by a soluble factor released by MN; (c) this or these
      factors are able to block the division of surrounding intraerythrocytic parasites
      at the one nucleus stage; (d) the critical triggering antigen(s) targeted by
      effective Abs would appear to be associated with the surface of merozoites, as
      opposed to that of infected red blood cells; (e) the MN receptor for Abs
      effective in ADCI is apparently Fc gamma RII, and not RI; (f) MN function is up-
      and down-regulated by interferon-gamma and interleukin 4, respectively; and (g)
      of several potential mediators released by MN, only tumor necrosis factor (TNF)
      proved of relevance. The involvement of TNF in defense may explain the recently
      described increased frequency of the TNF-2 high-expression promoter in
      individuals living in endemic regions despite its compromising role in severe
      malaria.

PMID- 7629504
TI  - Dimerization of soluble major histocompatibility complex-peptide complexes is
      sufficient for activation of T cell hybridoma and induction of unresponsiveness.
AB  - Major histocompatibility complex (MHC) class I molecules are cell-surface
      proteins that present peptides to CD8+ T cells. These peptides are mostly derived
      from endogenously synthesized protein. Recombinant, soluble MHC class I molecules
      were produced, purified, and loaded homogeneously with synthetic peptide. These
      MHC-peptide complexes were used to activate a T cell hybridoma. While monomers of
      MHC-peptide bound to the T cell, they showed no stimulatory activity. Dimers
      fully triggered the T cell hybridoma to secrete interleukin 2. This response was
      followed by a state in which the T cell was refractory to restimulation as a
      result of defective signal transduction through the T cell receptor.

PMID- 7629505
TI  - Inhibition of cartilage and bone destruction in adjuvant arthritis in the rat by
      a matrix metalloproteinase inhibitor.
AB  - Considerable evidence has associated the expression of matrix metalloproteinases
      (MMPs) with the degradation of cartilage and bone in chronic conditions such as
      arthritis. Direct evaluation of MMPs' role in vivo has awaited the development of
      MMP inhibitors with appropriate pharmacological properties. We have identified
      butanediamide, N4-hydroxy-2-(2-methylpropyl)-N1-[2-[[2-(morpholinyl)ethyl]-,[S-
      (R*,S*)] (GI168) as a potent MMP inhibitor with sufficient solubility and
      stability to permit evaluation in an experimental model of chronic destructive
      arthritis (adjuvant-induced arthritis) in rats. In this model, pronounced acute
      and chronic synovial inflammation, distal tibia and metatarsal marrow hyperplasia
      associated with osteoclasia, severe bone and cartilage destruction, and ectopic
      new bone growth are well developed by 3 wk after adjuvant injection. Rats were
      injected with Freund's adjuvant on day 0. GI168 was was administered systemically
      from days 8 to 21 by osmotic minipumps implanted subcutaneously. GI168 at 6, 12,
      and 25 mg/kg per d reduced ankle swelling in a dose-related fashion. Radiological
      and histological ankle joint evaluation on day 22 revealed a profound dose
      related inhibition of bone and cartilage destruction in treated rats relative to
      rats receiving vehicle alone. A significant reduction in edema, pannus formation,
      periosteal new bone growth and the numbers of adherent marrow osteoclasts was
      also noted. However, no significant decrease in polymorphonuclear and mononuclear
      leukocyte infiltration of synovium and marrow hematopoietic cellularity was seen.
      This unique profile of antiarthritic activity indicates that GI168 is osteo- and
      chondro-protective, and it supports a direct role for MMP in cartilage and bone
      damage and pannus formation in adjuvant-induced arthritis.

PMID- 7629506
TI  - Absence of extraocular muscle pathology in Duchenne's muscular dystrophy: role
      for calcium homeostasis in extraocular muscle sparing.
AB  - Duchenne muscular dystrophy (DMD) is characterized by clinical weakness and
      progressive necrosis of striated muscle as a consequence of dystrophin
      deficiency. While all skeletal muscle groups are thought to be affected,
      enigmatically, the extraocular muscles (EOM) appear clinically unaffected. Here
      we show that dystrophin deficiency does not result in myonecrosis or
      pathologically elevated levels of intracellular calcium ([Ca2+]i) in EOM. At
      variance with a previous report, we find no evidence for dystrophin-related
      protein/utrophin up-regulation in EOM. In vitro experiments demonstrate that
      extraocular muscles are inherently more resistant to necrosis caused by
      pharmacologically elevated [Ca2+]i levels when compared with pectoral
      musculature. We believe that EOM are spared in DMD because of their intrinsic
      ability to maintain calcium homeostasis better than other striated muscle groups.
      Our results indicate that modulating levels of [Ca2+]i in muscle may be of
      potential therapeutic use in DMD.

PMID- 7629507
TI  - Viral interleukin 10 (IL-10), the human herpes virus 4 cellular IL-10 homologue,
      induces local anergy to allogeneic and syngeneic tumors.
AB  - After the cloning of murine cytokine synthesis inhibitory factor, it was
      recognized that a homologous open reading frame was encoded within the Epstein
      Barr virus (human herpes virus 4). This viral protein has now been termed viral
      interleukin 10 (vIL-10) to reflect its protein sequence homology to "cellular" IL
      10 (cIL-10, either murine or human IL-10). It is now widely accepted that vIL-10
      shares many functions with cIL-10, principally, the ability to enhance survival
      of newly infected B cells and to diminish the production of IFN-gamma and IL-2
      during ongoing immune reactions. The immunomodulatory effect of locally secreted
      vIL-10 and murine IL-10 (mIL-10) was examined in tumor models using CL8-1 (a BL6
      melanoma cell line transfected with the H-2Kb class I gene) in syngeneic animals.
      Although parental BL6 tumor cells grow in immunocompetent syngeneic hosts, CL8-1
      are rejected. To achieve local secretion of vIL-10, we generated vIL-10
      retroviral vectors. While nontransduced CL8-1 cells (1 x 10(4)) failed to grow
      when injected intradermally in C57BL/6 mice, CL8-1 cells (1 x 10(4)) transduced
      with vIL-10 formed palpable tumors and eventually killed 80% of injected animals.
      Suppression of tumor rejection was also noted when CL8-1 tumors with or without
      vIL-10 transfection were admixed with syngeneic vIL-10-transfected fibroblasts
      and inoculated. Since the in vitro proliferation of the tumor was not altered
      after transduction with the vIL-10 gene and injection of vIL-10-transduced CL8-1
      does not affect the rejection of nontransduced CL8-1 inoculated at a distant
      site, local vIL-10 secretion appears to suppress the process of immune rejection
      of the target cells in a dose-dependent manner. Similar results were observed for
      the H-2b MCA105 sarcoma tumor model in allogeneic BALB/c mice (H-2d). Although
      all animals that received nontransfected MCA105 rapidly rejected these tumors,
      MCA105 sarcomas transfected with vIL-10 remained palpable for up to 37 d. The
      local immunosuppressive effect of gene-delivered vIL-10 could be neutralized by
      anti-human IL-10 monoclonal antibody or could be reversed by the systemic
      administration of IL-2 or IL-12. In marked contrast, mIL-10 transfection of CL8-1
      significantly suppressed tumor growth and frequently led to the rejection of
      tumor. Similar results were obtained for the murine tumor cell lines
      MCA102.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7629509
TI  - Adherence of pilus- Opa+ gonococci to epithelial cells in vitro involves heparan
      sulfate.
AB  - Neisseria gonorrhoeae attaches to host epithelial cells via pili and opacity
      associated (Opa) outer membrane proteins. Pilus- gonococci (Gc) of strain MS11
      adhere to both human and nonhuman cells, but only when particular Opa proteins
      are expressed; OpaA+ variants adhere best, OpaC+ variants are next best, and the
      seven other Opa+ variants adhere poorly or not at all. The adherence of OpaA+ Gc
      to Chinese hamster ovary (CHO) cells is inhibited by heparin or heparan sulfate
      (HS), but not by chondroitin sulfate. OpaA+ Gc do not adhere to CHO cells devoid
      of HS proteoglycans; low concentrations of heparin restore OpaA+ Gc adherence to
      these HS-deficient CHO cells and high concentrations inhibit it. 3H-heparin
      binding to whole Gc parallels their adherence abilities (OpaA+ > OpaC+ > OpaH+ >>
      Opas B, D, E, F, G, I = Opa- = 0). Opa proteins separated by SDS-PAGE also bind
      3H-heparin. These data suggest that adherence of pilus-, Opa+ Gc involves HS
      proteoglycan of eukaryotic cells.

PMID- 7629508
TI  - Functional roles of the transcription factor Oct-2A and the high mobility group
      protein I/Y in HLA-DRA gene expression.
AB  - The class II major histocompatibility complex gene HLA-DRA is expressed in B
      cells, activated T lymphocytes, and in antigen-presenting cells. In addition, HLA
      DRA gene expression is inducible in a variety of cell types by interferon-gamma
      (IFN-gamma). Here we show that the lymphoid-specific transcription factor Oct-2A
      plays a critical role in HLA-DRA gene expression in class II-positive B cell
      lines, and that the high mobility group protein (HMG) I/Y binds to multiple sites
      within the DRA promoter, including the Oct-2A binding site. Coexpression of HMG
      I/Y and Oct-2 in cell lines lacking Oct-2 results in high levels of HLA-DRA gene
      expression, and in vitro DNA-binding studies reveal that HMG I/Y stimulates Oct
      2A binding to the HLA-DRA promoter. Thus, Oct-2A and HMG I/Y may synergize to
      activate HLA-DRA expression in B cells. By contrast, Oct-2A is not involved in
      the IFN-gamma induction of the HLA-DRA gene in HeLa cells, but antisense HMG I/Y
      dramatically decreases the level of induction. We conclude that distinct sets of
      transcription factors are involved in the two modes of HLA-DRA expression, and
      that HMG I/Y may be important for B cell-specific expression, and is essential
      for IFN-gamma induction.

PMID- 7629510
TI  - Recognition of multiple peptide cores by a single T cell receptor.
AB  - We present evidence that a single T cell clone can recognize at least five
      different overlapping peptides, each with its distinct core structure, in the
      context of the same major histocompatibility complex (MHC) molecule. Distinct
      core residues are crucial for triggering the T cell receptor (TCR) in each case.
      These results suggest that the TCR (a) has multiple sets of contact residues for
      alternative peptide-MHC ligands, the binding to any one of which can trigger the
      cell; and/or (b) is able to attach to the peptide-MHC complex in more than one
      orientation. In this sense, the TCR is a multisubsite structure capable of being
      stimulated by a variety of peptide ligands associated with the same MHC
      molecules.

PMID- 7629511
TI  - Light chain replacement: a new model for antibody gene rearrangement.
AB  - A functional B cell antigen receptor is thought to regulate antibody gene
      rearrangement either by stopping further rearrangement (exclusion) or by
      promoting additional rearrangement (editing). We have developed a new model to
      study the regulation of antibody gene rearrangement. In this model, we used gene
      targeting to replace the J kappa region with a functional V kappa-J kappa light
      chain gene. Two different strains of mice were created; one, V kappa 4R, has a V
      kappa 4-J kappa 4 rearrangement followed by a downstream J kappa 5 segment, while
      the other, V kappa 8R, has a V kappa 8-J kappa 5 light chain. Here, we analyze
      the influence of these functional light chains on light chain rearrangement. We
      show that some V kappa 4R and V kappa 8R B cells only have the V kappa R light
      chain rearrangement, whereas others undergo additional rearrangements. Additional
      rearrangement can occur not only at the other kappa allele or isotype (lambda),
      but also at the targeted locus in both V kappa 4R and V kappa 8R. Rearrangement
      to the downstream J kappa 5 segment is observed in V kappa 4R, as is deletion of
      the targeted locus in both V kappa 4R and V kappa 8R. The V kappa R models
      illustrate that a productively rearranged light chain can either terminate
      further rearrangement or allow further rearrangement. We attribute the latter to
      editing of autoantibodies and to corrections of dysfunctional receptors.

PMID- 7629512
TI  - Analysis of mutations in immunoglobulin heavy chain variable region genes of
      microdissected marginal zone (MGZ) B cells suggests that the MGZ of human spleen
      is a reservoir of memory B cells.
AB  - The splenic marginal zone (MGZ), which surrounds the mantle zone (MTZ) in human
      splenic white pulp, contains a phenotypically and morphologically distinct
      population of B cells. The origin of MGZ B cells is uncertain. Whereas some
      experiments in rodents have suggested that they are a distinct cell lineage
      responsible for the immune response to T-independent type 2 antigens, others have
      suggested that they are memory B cells derived from a germinal center (GC)
      response. The progeny of a GC reaction is expected to have rearranged
      immunoglobulin (Ig) genes that are mutated. The distribution of mutations would
      be expected to reflect the selection of Ig by its affinity for antigen. We have
      analyzed rearranged Ig heavy chain variable region (VH) 6 and VH 4.21 genes in
      MGZ and MTZ B cells microdissected from frozen sections of human spleen to
      determine whether these genes have the properties of an affinity-selected memory
      B cell population. MTZ B cells contained germline Ig VH genes, confirming
      previous reports and providing an internal control for mutational analysis. MGZ B
      cells contained Ig VH genes that were mutated, showing that these cells had been
      subjected to a mutational mechanism characteristically active in the GC. The
      rearranged VH 6 genes showed patterns of mutation indicative of an antigen
      selection process, whereas the distribution of mutations in VH 4.21 genes was not
      characteristic of gene selection by conventional T-dependent antigen. Our studies
      provide the first evidence that the human splenic MGZ is a reservoir of memory B
      cells.

PMID- 7629513
TI  - Mast cells lacking the high affinity immunoglobulin E receptor are deficient in
      Fc epsilon RI gamma messenger RNA.
AB  - A population of cells that express mast cell markers, including the membrane
      protein p161, but that lack expression of the high affinity IgE receptor, Fc
      epsilon RI, can be routinely grown from bone marrow. Ionomycin, but not IgE
      immune complexes, causes these cells to release serotonin and to express IL-3 and
      IL-13 mRNA, consistent with their being FC epsilon RI-deficient mast cells. These
      p161+/Fc epsilon RI- mast cells expressed normal amounts of Fc epsilon RI alpha
      and beta chain mRNA, but extremely low levels of Fc epsilon RI gamma chain mRNA.
      In addition, this novel mast cell population expressed CD3 zeta chain mRNA, which
      p161+/Fc epsilon RI+ mast cells did not. CD3 zeta stable transfectants of Abelson
      murine leukemia virus-transformed p161+/Fc epsilon RI+ mast cells continued to
      express Fc epsilon RI. This strongly suggests that the failure of p161+/Fc
      epsilon RI- mast cells to express IgE receptors was not caused by the presence of
      CD3 zeta chain. Transfection of human Fc epsilon RI gamma cDNA into p161+/Fc
      epsilon RI- mast cells rescued IgE binding. These stable transfectants released
      serotonin in response to cross-linkage of Fc epsilon RI, demonstrating that the
      molecular defect of p161+/Fc epsilon RI- mast cells is indeed the loss of Fc
      epsilon RI gamma expression.

PMID- 7629514
TI  - Identification of Fc epsilon RIneg mast cells in mouse bone marrow cell cultures.
      Use of a monoclonal anti-p161 antibody.
AB  - A monoclonal hamster antibody (K-1) specific for a 161-kD mast cell surface
      glycoprotein was derived. p161 is expressed on normal and cultured mast cells and
      on some macrophages, but not on basophils or other hematopoietic cells. A
      population of Fc epsilon Rneg cells expressing p161 was found in short term
      cultures of bone marrow cells grown in interleukin (IL)-3. These cells were
      purified and propagated for extended periods in IL-3. They express c-kit and Fc
      gamma RII/III, contain alcian blue-positive granules and histamine, and secrete
      IL-3 in response to ionomycin treatment. Their morphology is consistent with that
      of mast cells. We propose that they represent Fc epsilon RIneg mast cells that
      can be detected and purified because of their p161 expression.

PMID- 7629516
TI  - Ceramide induces interleukin 6 gene expression in human fibroblasts.
AB  - We previously reported that ceramide, the immediate product of sphingomyelin
      hydrolysis, increases in response to interleukin (IL)-1 beta and plays a role in
      modulating IL-1 beta-mediated prostaglandin E2 production and cyclooxygenase gene
      expression in human fibroblasts (Ballou, L. R., C. P. Chao, M. A. Holness, S. C.
      Barker, and R. Raghow. 1992. J. Biol. Chem. 267:20044-20050). Here we describe
      the effects of ceramide in another IL-1 beta-mediated process in these cells, the
      induction of IL-6 production. We found that submicromolar concentrations of C2
      ceramide induced IL-6 gene expression and protein production as effectively as IL
      1 beta. Both D-erythro-C2-ceramide (a cell-permeable analogue of natural
      ceramide) and D-threo-C2-ceramide were potent inducers of IL-6 production, while
      neither L isomer of ceramide was effective. Compared with IL-1 beta-induced IL-6
      production, cells treated with ceramide or exogenous sphingomyelinase induced 82
      and 50% of maximal IL-1 beta-induced IL-6 levels by 6 h, respectively; by 24 h
      all three treatments induced similar levels of IL-6 production. Ceramide-induced
      IL-6 messenger RNA could be detected within 1 h of treatment and reached maximal
      levels by 24 h. These findings suggest that ceramide may play a role in the
      regulation of IL-6 gene expression.

PMID- 7629517
TI  - Amino acid substitutions can influence the natural killer (NK)-mediated
      recognition of HLA-C molecules. Role of serine-77 and lysine-80 in the target
      cell protection from lysis mediated by "group 2" or "group 1" NK clones.
AB  - Natural killer (NK) cells have been shown to express a clonally distributed
      ability to recognize HLA class I alleles. The previously defined NK clones
      belonging to "group 1" recognize HLA-C*0401 (Cw4) and other HLA-C alleles sharing
      Asn at position 77 and Lys at position 80. Conversely, the "group 2" NK clones
      recognize HLA-Cw*0302 (Cw3) and other HLA-C alleles characterized by Ser at
      position 77 and Asn at position 80. We assessed directly the involvement of these
      two residues in the capacity of NK cell clones to discriminate between the two
      groups of HLA-C alleles. To this end, Cw3 and Cw4 alleles were subjected to site
      directed mutagenesis. Substitution of the amino acids typical of the Cw3 allele
      (Ser-77 and Asn-80) with those present in Cw4 (Asn-77 and Lys-80) resulted in a
      Cw3 mutant that was no longer recognized by group 2 NK cell clones, but that was
      recognized by group 1 clones. Analysis of Cw3 or Cw4 molecules containing single
      amino acid substitutions indicates roles for Lys-80 in recognition mediated by
      group 1 clones and for Ser-77 in recognition mediated by group 2 clones. These
      results demonstrate that NK-mediated specific recognition of HLA-C allotypes is
      affected by single natural amino acid substitutions at positions 77 and 80 of the
      heavy chain.

PMID- 7629515
TI  - Pertussis toxin inhibits migration of B and T lymphocytes into splenic white pulp
      cords.
AB  - The normal migration route of B cells into follicular areas of spleen and lymph
      nodes is altered in the case of autoreactive cells that have bound self-antigen.
      To begin characterizing the molecular requirements for B cell migration into
      follicles, cells were treated with pertussis toxin (PTX), an inhibitor of
      signaling by many G protein-coupled chemokine receptors. Lymphocyte accumulation
      in the spleen is not inhibited by PTX and, therefore, the distribution of
      transferred cells was examined in this tissue. In contrast to untreated cells
      that localized predominantly in follicular areas within white pulp cords, PTX
      treated B cells failed to enter white pulp areas altogether and accumulated in
      the splenic red pulp. T cells were also excluded from white pulp cords and in the
      case of both cell types, the adenosine diphosphate-ribosylating subunit of the
      toxin was required to block white pulp entry. These findings implicate a G
      protein-coupled receptor in lymphocyte migration into splenic white pulp cords.
      Exclusion of PTX-treated cells from all organized areas of secondary lymphoid
      tissues raises the possibility that the association observed between PTX
      treatment and predisposition to autoimmune disease results from inhibition of
      tolerance mechanisms that normally operate within secondary lymphoid tissues.

PMID- 7629518
TI  - The protein product of the c-cbl protooncogene is phosphorylated after B cell
      receptor stimulation and binds the SH3 domain of Bruton's tyrosine kinase.
AB  - X-linked agammaglobulinemia, a B cell immunodeficiency, is caused by mutations in
      the Bruton's tyrosine kinase (Btk) gene. The absence of a functional Btk protein
      leads to a failure of B cell differentiation and antibody production. B cell
      receptor stimulation leads to the phosphorylation of the Btk protein and it is,
      therefore, likely that Btk is involved in B cell receptor signaling. As a
      nonreceptor tyrosine kinase, Btk is likely to interact with several proteins
      within the context of a signal transduction pathway. To understand such
      interactions, we have generated glutathione S-transferase fusion proteins
      corresponding to different domains of the human Btk protein. We have identified a
      120-kD protein present in human B cells as being bound by the SH3 domain of Btk
      and which, after B cell receptor stimulation, is one of the major substrates of
      tyrosine phosphorylation. We have shown that this 120-kD protein is the protein
      product of c-cbl, a protooncogene, which is known to be phosphorylated in
      response to T cell receptor stimulation and to interact with several other
      tyrosine kinases. Association of the SH3 domain of Btk with p120cbl provides
      evidence for an analogous role for p120cbl in B cell signaling pathways. The
      p120cbl protein is the first identified ligand of the Btk SH3 domain.

PMID- 7629519
TI  - Formation of simian immunodeficiency virus long terminal repeat circles in
      resting T cells requires both T cell receptor- and IL-2-dependent activation.
AB  - Although immunodeficiency viruses can enter resting CD4+ T lymphocytes,
      activation of T cells is required for complete viral cDNA synthesis and transport
      of double-stranded viral DNA to the nucleus. Cross-linking T cell receptors
      (TCRs) on resting CD4+ T cells induces reverse transcription of full-length
      simian immunodeficiency virus (SIV) genomes, but TCR engagement alone is
      insufficient to stimulate SIV DNA to move to the nucleus and form long terminal
      repeat (LTR) circles. Neither ligation of TCR or CD28 receptors nor interleukin 2
      (IL-2) alone induces formation of LTR circles; however, the combination of TCR
      ligation with either CD28 ligation or IL-2 doses. Anti-IL-2 serum inhibits the
      formation of LTR circles induced by cross-linking CD3 and CD28, but has no effect
      on the induction of increased viral reverse transcription. Thus, two signals
      appear to be required for immunodeficiency viruses to move to the T cell nucleus,
      one from the TCR to promote reverse transcription of the viral genome, the other
      through an IL-2-dependent process leading to formation of LTR circles.

PMID- 7629521
TI  - Down's syndrome and the links with Alzheimer's disease.

PMID- 7629520
TI  - Cloning and characterization of a new isoform of the interleukin 1 receptor
      antagonist.
AB  - By reverse transcriptase polymerase chain reaction on messenger RNA from human
      polymorphonuclear cells, we have isolated a sequence identical to the cDNA coding
      for intracellular interleukin 1 receptor antagonist (icIL-1ra), but containing an
      additional in-frame 63-bp sequence located three codons downstream of the
      translation start of icIL-1ra. This additional sequence is inserted between the
      first and second exon of the intracellular form, the latter of which is colinear
      with part of the first exon of the secreted form of IL-1ra. The additional
      sequence is coded by an extra exon located 2 kb downstream the first icIL-1ra
      specific exon. The complementary DNA sequence of the alternatively spliced form
      of icIL-1ra shows that the predicted protein differs from classical icIL-1ra in
      the NH2 terminus by insertion of a leaderless sequence of 21 amino acids rich in
      glycine and glutamic acid residues. Transcripts coding for this new form of icIL
      1ra were detected in activated fibroblasts, keratinocytes, and at low levels in
      myelomonocytic cells. The recombinant protein expressed in COS cells had an
      apparent molecular mass in sodium dodecyl sulfate polyacrylamide gel
      electrophoresis of 25 kD compared to 22 kD of classical icIL-1ra, and was mostly
      intracellular. The ability of this new form of icIL-1ra to inhibit IL-1 activity,
      in terms of induction of E-selectin and human immunodeficiency virus replication,
      was comparable to that of classical icIL-1ra. We propose to refer to this new
      form of icIL-1ra as icIL-1ra type II.

PMID- 7629522
TI  - Hyoscyamus niger (henbane).

PMID- 7629524
TI  - Electrocardiography in a patient with tremulant Parkinson's disease.

PMID- 7629523
TI  - Eye movements.

PMID- 7629525
TI  - Recurrent stroke after transient ischaemic attack or minor ischaemic stroke: does
      the distinction between small and large vessel disease remain true to type? Dutch
      TIA Trial Study Group.
AB  - The incidence and vascular type of recurrent ischaemic stroke was studied in
      patients with supratentorial transient ischaemic attacks or non-disabling
      ischaemic strokes, who were treated with aspirin (30 or 283 mg). Patients were
      divided into groups with small vessel disease (SVD) (n = 1216) or large vessel
      disease (LVD) (n = 1221) on the grounds of their clinical features and CT at
      baseline. Patients with evidence of both SVD and LVD (n = 180) were excluded from
      further analyses. During follow up (mean 2.6 years) annual stroke rate was 3.6%
      in both groups. Of the 107 patients with SVD at baseline who had recurrent
      strokes, 83 proved to have an identifiable infarct: 30 (28%) again had a small
      vessel infarct, 39 (36%) had a large vessel ischaemic stroke and in 14 (13%) the
      recurrent ischaemic stroke was in the posterior fossa. Of the 110 patients with
      LVD at baseline and recurrent stroke, 91 had an identifiable infarct: 67 (61%)
      again had a large vessel ischaemic stroke, 16 (15%) had a small vessel ischaemic
      stroke, and eight (7%) had the recurrent ischaemic stroke in the posterior fossa.
      Thus patients with a transient ischaemic attack or non-disabling ischaemic stroke
      caused by LVD were more likely to have an ischaemic stroke of the same vessel
      type during follow up than patients with SVD (relative risk 2.2; 95% confidence
      interval 1.5-3.4). Possible explanations for this difference are: (1) patients
      with a small vessel ischaemic stroke at baseline had both SVD and LVD or were
      misdiagnosed; (2) recurrent small vessel ischaemic stroke may have occurred more
      often than reported, because they were silent or only minimally disabling; (3)
      recurring large vessel ischaemic strokes occurring in patients initially
      diagnosed as having SVD might have been related to potential cardiac sources of
      emboli that had not been previously recognized; (4) the antiplatelet drug aspirin
      (30 or 283 mg) prescribed in this patient group may have prevented thrombosis in
      small vessels better than in large vessels.

PMID- 7629526
TI  - Comparison of CT in patients with cerebral ischaemia with or without non
      rheumatic atrial fibrillation. European Atrial Fibrillation Trial and Dutch T I A
      Trial Study Groups.
AB  - In an attempt to distinguish between the CT characteristics of strokes of
      presumed cardioembolic origin and strokes caused by arterial disease, a
      comparison was made between the baseline CT of two prospective cohorts of
      patients with transient ischaemic attack or minor ischaemic stroke, with (n =
      985) or without (n = 2987) non-rheumatic atrial fibrillation (NRAF). Of the
      patients with NRAF 54% had evidence of cerebral infarction v 41% of the controls
      (patients with sinus rhythm (SR); odds ratio (OR) 1.7; 95% confidence interval
      (95% CI) 1.4-1.9). Patients with NRAF more often had multiple infarcts (OR 1.4;
      95% CI 1.1-1.8), and more often infarcts that were not related to current
      neurological symptoms (OR 1.5; 95% CI 1.2-1.8). For symptomatic infarcts,
      patients with NRAF more often had cortical end zone infarcts (OR 3.1; 95% CI 2.6
      3.8) and cortical border zone infarcts (OR 1.9; 95% CI 1.3-2.9) than patients
      with SR. Conversely, symptomatic small deep infarcts (lacunae) were more often
      seen in patients with SR (OR 3.9; 95% CI 2.8-5.4). Multivariate analyses showed
      that all these findings were independent of differences in baseline
      characteristics between the two study groups. The CT characteristics overlapped
      and did not allow a reliable distinction between cardioembolic and
      atherosclerotic causes of stroke in patients with NRAF.

PMID- 7629527
TI  - Cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy: a clinicopathological and genetic study of a Swiss family.
AB  - This paper reports a Swiss family affected by a cerebral autosomal dominant
      arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) linked
      to chromosome 19q12. In three generations several members of this family had
      recurrent stroke-like episodes and, some developed subcortical dementia, migraine
      like headaches, and depression. The clinically affected family members had
      multiple subcortical infarcts and diffuse leukoencephalopathy on MRI. Necropsy of
      one patient showed a distinctive non-amyloid and non-atherosclerotic angiopathy
      of small cerebral and leptomeningeal arteries with concentric depositions of a
      basophilic granular material replacing the smooth muscle cells of the media.
      Linkage analysis with five chromosome 19 markers spanning the estimated CADASIL
      interval showed the absence of any recombinant and positive Lod scores, highly
      suggestive of linkage of this condition to the CADASIL locus. CADASIL might be an
      underestimated cause of familial stroke and should be considered in the
      differential diagnosis of hereditary stroke.

PMID- 7629528
TI  - Multiple system atrophy presenting as parkinsonism: clinical features and
      diagnostic criteria.
AB  - To evaluate the possibility that parkinsonian signs may be the only presenting
      feature of multiple system atrophy (MSA), parkinsonian patients were studied who
      had no atypical clinical signs and had no symptoms of autonomic dysfunction, but
      who reported that they had not experienced the anticipated good response to
      dopaminergic treatment. These stringent criteria identified 20 patients from a
      series of 298 consecutive parkinsonian outpatients. The following clinical
      pointers were analysed: (a) rate of disease progression; (b) symmetry of
      parkinsonian symptoms and signs; (c) occurrence of resting tremor during the
      first three years from onset. In addition, all patients underwent (d) acute and
      chronic challenge with dopaminergic drugs; (e) cardiovascular reflex autonomic
      function tests; (f) high field MRI. Rapid progression of disease was seen in 45%
      of patients, onset was symmetric in 25%, tremor was absent at onset in 70%,
      response to dopaminergic drug challenges was inadequate in 40%, abnormal
      cardiovascular reflexes occurred in 50%, and some abnormal MRI finding occurred
      in 35% of cases. Each of these features was equally weighted by giving to each
      patient a 0 to 6 point score corresponding to the number of abnormal findings.
      Fifteen patients scoring higher than 1 were considered at risk for having MSA:
      five of them were classified as clinically possible (score 2), six as clinically
      probable (score 3-4), and four patients were classified as clinically definite
      multiple system atrophy (score 5). The six pointers considered were variably
      combined in each patient, none of them being universally abnormal in patients
      with high scores. The patients were followed up for a mean 2.1 (SEM 0.65) years.
      All but one of the 10 patients prospectively classified as probable or definite
      MSA developed unequivocal clinical signs of fully symptomatic MSA. A receiver
      operator characteristic cure was plotted for the prospective score based on
      follow up diagnosis. The best compromise for trade off between sensitivity and
      specificity was a cut off value at a score of 3. The sensitivity and specificity
      of the individual pointers considered to predict fully symptomatic MSA varied
      considerably, and no single item could predict whether patients presenting with
      just parkinsonian signs went on during the two year follow up period to develop
      fully symptomatic MSA. Instead, the number of abnormalities offered a predictive
      value for the clinical prognosis of these parkinsonian patients.

PMID- 7629529
TI  - Diagnostic value of paraclinical tests in multiple sclerosis: relative
      sensitivities and specificities for reclassification according to the Poser
      committee criteria.
AB  - The yield of paraclinical tests was evaluated in a prospective study of 189
      consecutive patients referred for suspected multiple sclerosis (142 patients with
      multiple sclerosis, 47 non-multiple sclerosis patients on discharge). Patients
      were first classified according to the Poser criteria by the clinical findings.
      Subsequently, the results of paraclinical tests (cranial MRI, visually evoked
      potentials (VEPs), somatosensory evoked potentials by tibial nerve stimulation
      (SSEPs), motor evoked potentials (MEPs), and analysis of CSF for oligoclonal
      banding and IgG-index (CSF)) were taken into account. The percentage of
      reclassified patients (reclassification sensitivity, RS) was always lower than
      the percentage of abnormal results (diagnostic sensitivity, DS), and the
      divergence of RS v DS differed between the tests (60% v 84% in MRI, 31% v 77% in
      CSF, 29% v 37% in VEPs, 20% v 68% in MEPs, and 12% v 46% in SSEPs respectively).
      False reclassifications of non-multiple sclerosis patients to multiple sclerosis
      would have occurred with all tests (MRI: six of 47 patients, (reclassification
      specificity 88%); CSF: one (98%); VEPs: two (96%); MEPs: two (96%); SSEPs: four
      (91%); P < 0.05). Although MRI had superior diagnostic capacity, 57 of the 142
      patients with multiple sclerosis were not reclassified by the MRI result, 12 of
      whom were reclassified by CSF and 18 by one of the evoked potential (EP) studies.
      Of the 98 patients not reclassified by CSF, 53 were reclassified by MRI and 39 by
      EPs. The results suggest that for the evaluation of paraclinical tests in
      suspected multiple sclerosis, comparison of diagnostic sensitivities is
      inappropriate. In general, a cranial MRI contributes most to the diagnosis;
      however, due to its comparatively low specificity and its considerable number of
      negative results, EP or CSF studies are often useful to establish the diagnosis
      of multiple sclerosis.

PMID- 7629530
TI  - Leber's "plus": neurological abnormalities in patients with Leber's hereditary
      optic neuropathy.
AB  - Previous studies suggest that Leber's hereditary optic neuropathy (LHON) may be a
      systemic disorder with manifestations in organs other than the optic nerves. To
      evaluate nervous system involvement 38 men and eight women with LHON were re
      examined. The patients were divided into three groups according to mtDNA analysis
      -namely, patients with the 11778 or with the 3460 mutation and patients without
      these primary mutations. Fifty nine per cent of patients had neurological
      abnormalities but there was no significant difference between the three groups.
      Movement disorders were the most common finding; nine patients had constant
      postural tremor, one chronic motor tic disorder, and one parkinsonism with
      dystonia. Four patients had peripheral neuropathy with no other evident cause.
      Two patients had a multiple sclerosis-like syndrome; in both patients MRI showed
      changes in the periventricular white matter. Thoracic kyphosis occurred in seven
      patients, five of whom had the 3460 mutation. In one patient the 3460 mutation
      was associated with involvement of the brain stem. It is suggested that various
      movement disorders, multiple sclerosis-like illness, and deformities of the
      vertebral column may associate pathogenetically with LHON.

PMID- 7629531
TI  - Impairment, disability, or handicap in peripheral neuropathy: analysis of the use
      of outcome measures in clinical trials in patients with peripheral neuropathies.
AB  - Outcome measures can be classified into measures of impairment, disability, and
      handicap. To investigate the biological effect of treatment, measures of
      impairment are appropriate. Studies investigating whether patients benefit from
      treatment in terms of improvement of functional health, however, require
      disability or handicap measures. In a review of the medical literature between
      1978 and 1993, 73 controlled intervention studies in patients with peripheral
      neuropathies were found. Disability or handicap measures were used in two of 54
      studies in patients with diabetic neuropathy, in two of six studies in patients
      with chronic inflammatory demyelinating polyneuropathy, in none of five studies
      in a mixed group of patients, and in all eight studies in patients with Guillain
      Barre syndrome. The limited use of disability and handicap measures in patients
      with diabetic and mixed neuropathies can be explained by the experimental nature
      of most studies. In four of six studies, however, in patients with chronic
      inflammatory demyelinating polyneuropathy or neuropathy associated with
      monoclonal gammopathy that were designed to assess effectiveness of treatment,
      the choice of outcome measures was not appropriate. It is concluded that in the
      design of intervention studies in patients with peripheral neuropathy more
      attention should be paid to a proper choice of suitable outcome measures to
      assess the effectiveness of treatment.

PMID- 7629533
TI  - Application of the polymerase chain reaction to monitor Mycobacterium
      tuberculosis DNA in the CSF of patients with tuberculous meningitis after
      antibiotic treatment.
AB  - The polymerase chain reaction (PCR) was used to detect Mycobacterium tuberculosis
      DNA in 29 CSF specimens from seven patients with tuberculous meningitis after the
      start of antituberculous chemotherapy. Ten of the 13 CSF specimens taken from
      these patients with an initial treatment of three weeks were positive for the PCR
      study. By contrast, only one of the other 16 CSF specimens taken from patients
      treated for more than three weeks was positive. This study shows that M
      tuberculosis DNA can exist in the CSF of a patient with tuberculous meningitis
      for three weeks after treatment and that PCR can still be a sensitive method to
      detect M tuberculosis DNA in the CSF after the start of treatment in patients
      with tuberculous meningitis.

PMID- 7629532
TI  - Relation between education and dementia: the role of test bias revisited.
AB  - Several authors have suggested that dementia screening tests may be biased
      against low levels of education, whereas others find that a low level of
      education is a genuine risk factor for dementia. The present paper attempts to
      reconcile these conflicting views by examining item bias and test bias indices of
      the mini mental state examination (MMSE). Psychometric calculations and receiver
      operating characteristics (ROC) analyses of sensitivity and specificity as
      performed by earlier studies were replicated and extended from the database of
      the Amsterdam Study of the Elderly. This is a population survey on cognitive
      decline and dementia (age range 65-84). Subjects with a low level of education
      (primary school) were compared with better educated subjects (at least some
      secondary education). Cases were matched by age and sex. The results indicate
      that the MMSE is not educationally biased as far as item characteristics,
      reliability, and construct validity are concerned. Yet its predictive validity as
      a screening test for dementia is educationally biased. This bias will effectively
      be eliminated with a two point higher cut off score for the subjects whose
      education extends beyond primary school. Even after such score correction, a low
      level of education probably remains a genuine risk factor for dementia.

PMID- 7629534
TI  - Adult onset idiopathic torsion dystonia is excluded from the DYT 1 region (9q34)
      in a Swedish family.
AB  - A gene (DYT1) for early onset idiopathic torsion dystonia was mapped to
      chromosome 9q34 in non-Jewish and Jewish families. The DYT1 gene region has been
      excluded in other families with adult onset and cervical or cranial onset
      idiopathic torsion dystonia from the United States, Great Britain, and France.
      The role of DYT1 in a Swedish family with adult onset idiopathic torsion dystonia
      in four generations was examined. The disease seems to be inherited in an
      autosomal dominant mode with reduced penetrance in this family. There were 10
      affected family members, with a mean age of onset of 27 (range 18 to 50) years.
      The disease showed variable expression, with focal, multifocal, and generalised
      forms of dystonia in different family members. Genetic analysis excluded the
      chromosomal region containing the DYT1 locus as being responsible for dystonia in
      this family.

PMID- 7629535
TI  - Some doctor and patient opinions.

PMID- 7629536
TI  - Palmaris brevis spasm syndrome.
AB  - Palmaris brevis spasm syndrome is a rare and benign condition of localised
      muscular hyperactivity. In five men, the hypothenar eminence underwent
      spontaneous, irregular, tonic contractions of the palmaris brevis muscle. An EMG
      showed spontaneous high frequency discharges of normal motor units, without
      evidence of neuropathy or of nerve compression. This syndrome resembles other
      restricted muscle hyperactivity syndromes although there are some differences.
      Curiously, the palmaris brevis muscle is not under voluntary control. The
      mechanism of the syndrome could be an ephaptic transmission possibly secondary to
      the transient and repeated stretching of the ulnar nerve superficial branch. In
      one patient a root compression was the probable origin.

PMID- 7629538
TI  - A note on Claude Bernard-Horner's syndrome.

PMID- 7629537
TI  - Prospective study of relations between cortical Lewy bodies, poor eyesight, and
      hallucinations in Alzheimer's disease.
AB  - The presence of hallucinations is included in some, but not all, of the sets of
      clinical diagnostic criteria that have been proposed for dementia associated with
      cortical Lewy bodies. These criteria were developed from retrospective casenote
      analyses. This prospective, longitudinal study suggests that, in patients with
      Alzheimer's disease, cortical Lewy bodies are associated with more persistent and
      severe hallucinations, independently of any association with severity of
      cognitive decline. Poor eyesight contributes to the severity but not the
      persistence of the hallucinations.

PMID- 7629539
TI  - Chronic inflammatory demyelinating polyneuropathy mimicking a lumbar spinal
      stenosis syndrome.
AB  - A patient with chronic inflammatory demyelinating polyneuropathy (CIDP)
      established by biopsy developed cauda equina symptoms due to swelling of the
      nerve roots in the lumbar spinal canal. Magnetic resonance imaging of the lumbar
      spine showed profoundly thickened nerve roots from the level of the conus
      medullaris, filling the caudal thecal sac. Immunosuppressant treatment produced
      partial clinical and radiological resolution. This case shows that spinal
      compressive syndromes may occur in acquired hypertrophic neuropathies as well as
      in hereditary motor and sensory neuropathy and expands the range of the clinical
      presentation of CIDP.

PMID- 7629540
TI  - Ciguatera fish poisoning: also in Europe.

PMID- 7629541
TI  - Botulinum toxin in the management of paradoxical activity of jaw muscles.

PMID- 7629542
TI  - Treatment of severe tetanus by continuous intrathecal infusion of baclofen.

PMID- 7629543
TI  - Ceftriaxone treatment of penicillin resistant neurosyphilis in alcoholic
      patients.

PMID- 7629544
TI  - Absence of REM sleep and altered non-REM sleep caused by a haematoma in the
      pontine tegmentum.

PMID- 7629545
TI  - Recurrence of cluster headaches presenting with a virtually painless Horner's
      syndrome.

PMID- 7629546
TI  - Optic neuritis in cerebral toxocariasis.

PMID- 7629547
TI  - Herpes zoster meningoencephalitis without rash: varicella zoster virus DNA in
      CSF.

PMID- 7629548
TI  - Alexander Ypsilante (1792-1832)

PMID- 7629549
TI  - Angiotropic lymphoma in the differential diagnosis of systemic vasculitis.

PMID- 7629550
TI  - Genetics of streptomycin resistance in methicillin-sensitive multiply-resistant
      Staphylococcus aureus.
AB  - Streptomycin resistance was detected in 17 of 20 multiply-resistant
      Staphylococcus aureus isolates from a hospital in a southeastern Nigerian town.
      The isolates were uniformly sensitive to methicillin, erythromycin, gentamicin,
      mupirocin, ciprofloxacin and vancomycin but produced beta-lactamase and were
      resistant to other antimicrobial agents and harbored different plasmids which
      ranged in size and number from 1.0 to c, 40 kb and one to six respectively.
      Curing and transfer experiments demonstrated that streptomycin resistance (Smr)
      was located on plasmids in 15 of the 17 isolates. 16 Smr plasmids were isolated
      and characterized. They belonged to three distinct groups based on size and
      resistance phenotypes. Eight 4.4 kb plasmids encoded Smr only, three 4.7 kb
      plasmids encoded resistance to streptomycin and chloramphenicol (SmCm) and five
      23.8 kb plasmids encoded resistance to streptomycin, kanamycin, neomycin, cadmium
      and beta-lactamase production (CPKNS). Restriction endonuclease analysis
      demonstrated that the 4.4 kb Smr plasmids were similar to one another and
      indistinguishable from pUB109, an incompatibility group 5 Smr plasmid, suggesting
      that they may also belong to incompatibility group 5. The SmCm and the CPKNS
      plasmid groups also gave identical restriction patterns with single and double
      enzyme digests. Further transfer experiments with one of the SmCm plasmids led to
      the isolation of a 4.4 kb Smr plasmid which was indistinguishable from the other
      4.4 kb plasmids, suggesting that the SmCm plasmids are natural recombinants
      between a streptomycin and chloramphenicol resistance plasmid. The results
      demonstrate a multiple origin of streptomycin resistance in the S. aureus
      population studied.

PMID- 7629551
TI  - Transferable resistance to cefotaxime in nosocomial Klebsiella pneumoniae and
      Escherichia coli strains due to their production of extended-spectrum beta
      lactamase in Slovakia.
AB  - Transferable resistance to cefotaxime was demonstrated in 21 nosocomial strains
      of Klebsiella pneumoniae and Escherichia coli subsequently isolated from patients
      in two large University clinics. Using the double-disk diffusion test, we could
      detect, in each such strain, as well as in E. coli 3110 K-12 transconjugants
      after the transfer, the production of an Extended Spectrum Beta-Lactamase (ESBL).
      Ceftibuten was demonstrated to be effective against the majority of strains
      studied.

PMID- 7629552
TI  - Comparative evaluation of orally active antibiotics against community-acquired
      pathogens: a multi-center study in five Mediterranean countries.
AB  - In 5 Mediterranean countries 7902 pathogens, all isolated in 1992 and 1993 from
      community-acquired infections, were studied for susceptibility to the following
      orally active antibiotics: penicillin G, ampicillin, ampicillin + sulbactam,
      amoxycillin + clavulanic acid (both 2:1 ratio), cefalexin, cefaclor, cefuroxime,
      cefetamet, doxycycline and erythromycin. Ten centers in Italy, 4 centers in
      Greece, 3 centers in Spain, and 1 center in Lebanon and Saudi Arabia contributed
      to this study; all centers used performed standardized microtiter panels
      (Sceptor, BBL, Heidelberg, FRG). The most frequently isolated pathogens were
      Escherichia coli (n = 1267), Proteus mirabilis (n = 843), Klebsiella pneumoniae
      (n = 771), enteric Salmonella spp. (n = 629), Enterobacter cloacae (n = 486),
      Citrobacter freundii (n = 383), Streptococcus agalactiae (n = 346), Haemophilus
      influenzae (n = 298), Streptococcus pyogenes (n = 294), Streptococcus pneumoniae
      (n = 246), Klebsiella oxytoca (n = 243), and Shigella spp. (n = 185). Statistical
      analysis was performed for each of the above countries and for all pooled data
      available. The penicillin antibiotics were the most active compounds against the
      gram-positive cocci, exceeding the MIC90 values 2- to 8-fold over all
      cephalosporins. Regarding the gram-negatives (above all Klebsiella spp.)
      cefetamet was by far the most active compound (MIC90 = 1 mg/l). Regarding the
      percentage of resistant isolates, there were no striking discrepancies between
      the centers and countries involved in this study. There was, however, complete
      cross-resistance in penicillin-resistant S. pneumoniae isolates (MIC90 = 2 mg/l).
      By far the majority of the penicillin-resistant pneumococci showed additional
      resistance to doxycycline and erythromycin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7629553
TI  - Staphylococcus epidermidis isolation and antibiotic resistance in a neonatal
      intensive care unit.
AB  - Bacterial ecology was studied in 1114 newborns (355 at term, 759 preterm)
      admitted to a neonatal intensive care unit (NICU) during a three year period.
      Bacterial samples were taken in each newborn from external ear canal, pharynx and
      eyes in all patients, and from endotracheal tube, umbilical catheter and blood in
      selected patients. The predominant flora was characterized by gram-positive
      microorganisms (63.53%), Staphylococcus epidermidis representing 34.68% of all
      isolated strains. S. epidermidis isolation increased significantly with time (p <
      0.002) and was highest in summer. The percentage of S. epidermidis resistant
      strains to oxacillin (63.8%) and to amikacin (17.8%) was high. This is the
      antimicrobial combination we commonly employ as empirical treatment of suspected
      bacterial infection in our NICU. Knowledge of characteristics of local microbial
      flora seems important in order to optimize preventive and therapeutic policies
      for neonatal infections.

PMID- 7629554
TI  - DD-peptidases and beta-lactamases: catalytic mechanisms and specificities.
AB  - DD-peptidases and beta-lactamases share several common properties, including the
      formation of an acylenzyme intermediate in their catalytic pathways. In their
      interactions with beta-lactam antibiotics, the stability of this intermediate is
      much higher with the peptidases than with the beta-lactamases. The structural
      factors responsible for this difference have not been identified. The evolution
      of beta-lactamases is taking place before our eyes, since mutants are constantly
      selected which can hydrolyze the molecules newly introduced as "beta-lactamase
      resistant" in the chemotherapeutic arsenal.

PMID- 7629555
TI  - Antiviral activity of S-7HNa on the infectivity and replication of herpes simplex
      virus type 1 in cultured cells.
AB  - The effect of sodium salt of the acid related to ester S-7 (i.e. S-7HNa) on the
      infectivity and replication of herpes simplex virus type 1 in Vero cultured cells
      was studied. S-7HNa, at the highest concentration lacking cytotoxicity (10 mM),
      produced, at various inocula, a 70% inhibition of HSV-1 infectivity with respect
      to the plaque formation detected in control infected cultures. This inhibitory
      activity was substantiated by studies on progeny production. S-7HNa revealed a
      therapeutic index higher than that of the correlative ester (S-7).

PMID- 7629556
TI  - Effects of Aspergillus terreus extract on herpes simplex 1 virus replication.
AB  - In this study we reported about the antiviral activity of Aspergillus terreus
      alcohol extract against Herpes simplex type 1 virus. This activity is dose
      dependent, is related to the concentration of the challenging virus and depends
      particularly on a proteic fraction of 5-10 Kda. Optimal effects were observed
      with doses ranging from 25 to 6.25 micrograms/ml for crude alcohol extract and up
      to 3 micrograms/ml for 5-10 Kda fraction. Moreover, antiviral activity was
      evident in viral replication, but not on virus out of the cells. An increased 3H
      thymidine incorporation was noted on infected cells treated with the extract and
      this effect may suggest an intracellular accumulation of viral DNA in the absence
      or reduction of virion production.

PMID- 7629557
TI  - Evaluation of the effects of pefloxacin on platelet aggregation in vitro and ex
      vivo in patients suffering from chronic bronchitis.
AB  - The effects of pefloxacin on adenosine-diphosphate (ADP) and collagen-induced
      human platelet aggregation in vitro and ex vivo in patients suffering from
      chronic bronchitis were investigated. In the in vitro study carried out on
      platelets from 12 healthy volunteers, pefloxacin had no effect on platelet
      function even at a concentration of 10 mg/ml, which is 1,500 times higher than
      that reached in vivo. In the ex vivo study carried out in 10 patients, who
      received pefloxacin twice daily for 7-10 days as 400 mg oral dose, the drug did
      not influence platelet aggregation up to 24 hours after administration of the
      last oral dose.

PMID- 7629558
TI  - Biapenem versus imipenem in the treatment of experimental intraabdominal
      infections.
AB  - A reproducible experimental model of intraabdominal infections in rats has been
      devised in order to simulate intraabdominal infections in patients. The
      experimental model was used to compare the efficacy of biapenem with imipenem.
      Three groups of animals were used, each group consisting of 20 animals.
      Antibacterial agents were given by injection initially 1 h after surgery and then
      at 12 h intervals for 12 days. The drugs and amounts of agents given per dose
      were biapenem 10 mg and imipenem 10 mg, respectively. The control group received
      0.9% sterile saline. 80% of the untreated animals died within 3 days. Animals
      treated with biapenem or imipenem had a significantly decreased mortality and
      increased cure rates during the experimental period. Only two animals in the two
      treatment groups died. Biapenem seems to be useful in the treatment of
      intraabdominal infections.

PMID- 7629559
TI  - Determination of plasma concentrations of amikacin in patients of an intensive
      care unit.
AB  - Considering the low therapeutic index of the aminoglycosides it is mandatory to
      monitor serum concentrations (SC) either to obtain therapeutic levels or to avoid
      toxic levels. The SC of amikacin (AMK) was evaluated in 24 inpatients in an
      intensive care unit of Hospital Sao Joao, mean age (+/- SD) 45.5 +/- 18.57 years.
      In 62.5% of the patients it was shown that SC (mean +/- SD, 16.87 +/- 1.62) was
      inferior to the therapeutic range. In 33.3% the values (SC 25.85 +/- 3.77) were
      within the therapeutic window (> 20 micrograms/ml; < 35 micrograms/ml). Only 1
      patient attained toxic levels (> 35 micrograms/ml). In 4 of the patients with
      initial SC < 20 micrograms/ml, dosage was adjusted and thereafter therapeutic
      value was obtained (SC 24.65 +/- 3.38). The relation between the administered
      dose and the dosage usually recommended (weight X 15mg/day) was calculated. In
      the majority of our patients (the so-called "critically ill patients") the
      recommended dosages of AMK need to be increased in order to get the desired SC.
      In the population of this study a dosage of about 120% relative to the initial
      recommended dosage was necessary.

PMID- 7629560
TI  - Pulmonary penetration of ceftazidime.
AB  - For an antibiotic to be effective in lower respiratory tract infections, it
      should be available in adequate concentrations in respiratory tissues and fluids.
      Cephalosporins usually achieve modest concentrations in the respiratory tract. In
      this study we have determined the pulmonary penetration of intramuscularly
      administered ceftazidime (a single dose of 1 g). Levels of ceftazidime in
      bronchial secretions (BS), bronchial mucosa (BM), epithelial lining fluid (ELF),
      and serum (S) were measured by microbiological assay in 25 patients suffering
      from acute exacerbation of chronic bronchitis who were divided into 5 groups of 5
      subjects according to sampling time (1, 2, 4, 8 and 12 hours after the
      administration of the antibiotic). The peak S level was high (39.89 +/- 10.42
      micrograms/ml at 1 hour) and mean S concentrations decreased slowly and were
      still detectable at 12 hours (1.07 +/- 0.45 microgram/ml). In all other samples,
      mean concentrations were in excess of the ceftazidime minimum inhibitory
      concentrations (MICs) for many relevant respiratory pathogens (Haemophilus
      influenzae 0.15 microgram/ml; Moraxella catarrhalis 0.06 micrograms/ml;
      Streptococcus pneumoniae 0.15 micrograms/ml; Klebsiella pneumoniae 0.4
      microgram/ml). Concentrations in BM (7.05 +/- 2.38, 8.14 +/- 2.23, 6.40 +/- 1.63,
      4.06 +/- 0.99 and 0.45 +/- 0.27 microgram/g) were higher than that in BS (6.87 +/
      1.96, 6.54 +/- 1.84, 3.52 +/- 1.23, 1.56 +/- 0.92 and 0.23 +/- 0.19
      microgram/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7629561
TI  - Effects of age-targeted treatment of intestinal parasite infections in Serbia.
AB  - A survey of intestinal parasite infections in school-children throughout Serbia
      revealed an area of endemic infection where 31% of the children examined were
      found to be infected with Giardia lamblia, Enterobius vermicularis, Ascaris
      lumbricoides and Trichuris trichiura. All infected children were treated with
      metronidazole for giardiasis and mebendazole for helminthic infections. A post
      chemotherapy survey was performed 3 months later to assess the efficacy of
      treatment, showing a decrease in the prevalence of all species, thus indicating
      drug efficacy of 66-100%. A second survey, performed 13 months after chemotherapy
      to assess the rates of reinfection, showed that only Ascaris lumbricoides
      prevalence returned to the pre-treatment level. The results of this field study
      prove chemotherapy to be an important tool in the control of intestinal parasite
      infections.

PMID- 7629562
TI  - Treatment with ribavirin+alpha interferon in HCV chronic active hepatitis non
      responders to interferon alone: preliminary results.
AB  - Alpha interferon (IFN-alpha) represents the best therapy for HCV active chronic
      hepatitis, but only 25% of treated patients achieve a complete recovery. Several
      attempts have been made to increase this percentage. The objective of our study
      is to verify whether the combination ribavirin (R)+ IFN-alpha can lead to
      positive results in non-responders to treatment with IFN-alpha alone. The
      preliminary results for 5 subjects, all non-responders to IFN, treated with R+
      IFN for 60 days and then IFN alone for 4 months more show that during the R+IFN
      treatment, 2 subjects presented a reduction in transaminase; a month after the
      suspension of R, ALT returned to pre-treatment values. The results are
      preliminary but we can say that this combination in the proposed doses and times
      in these subjects, cannot be considered adequate to modify the natural course of
      this disease.

PMID- 7629563
TI  - Varicella in immunocompetent children in the first two years of life: role of
      treatment with oral acyclovir. Italian Acyclovir-Chickenpox Study Group.
AB  - An open multicenter study has been carried out to evaluate efficacy and
      tolerability of oral acyclovir in the treatment of varicella in immunocompetent
      patients in the first two years of life. Fifty-three children aged 3-24 months
      received acyclovir at 80 mg/Kg/day in four divided doses for 4 to 6 days; 24 of
      them were treated in the first 24 hours following disease onset, while the
      remaining 29 patients were enrolled within 48 hours. The assessment of evolution
      of disease signs and symptoms showed a rapid resolution of fever, itching and
      other constitutional symptoms, with interruption of vesicle formation and
      acceleration of cutaneous healing processes. No statistically significant
      differences have been demonstrated as to disease progression between patients
      treated in the first 24 hours, when compared with subjects receiving acyclovir in
      the following 24 hours. Acyclovir confirmed its excellent clinical and laboratory
      safety profile. By acting favorably on both the duration and severity of disease
      signs and symptoms, acyclovir treatment should be recommended in young children
      and infants with varicella, since a higher incidence of severe and complicated
      disease has been observed in these patient groups.

PMID- 7629564
TI  - Modulation of acute myeloblastic leukemia (AML) cell proliferation and blast
      colony formation by antisense oligomer for IL-1 beta converting enzyme (ICE) and
      IL-1 receptor antagonist (IL-1ra).
AB  - In the present study we investigated the effects of IL-1 antagonism on the
      autonomous growth of cells in acute myeloblastic leukemia (AML). To examine the
      role of pro-IL-1 processing, antisense technology was employed with 16-mer
      phosphorothioate oligodeoxynucleotide directed against human IL-1 beta converting
      enzyme (ICR) in 7 randomly selected AML cases. The addition of 10-75 microM of
      antisense oligonucleotide (but not of control oligonucleotide) significantly
      inhibited spontaneous proliferation of bone marrow- (BM) and peripheral blood-
      (PB) derived low density leukemic cells in a dose-dependent way. Similarly,
      spontaneous as well as induced CFU-AML colony formation was inhibited by human
      ICE antisense oligonucleotide with sample-to-sample variability. In separate
      experiments, in order to examine the effects of blockade of endogenously produced
      IL-1 to IL-1 receptors, the functional activity of human recombinant IL-1
      receptor antagonist (IL-1ra) was tested. Continuous exposure to high
      concentrations of IL-1ra (up to 100 micrograms/ml) produced dose-dependent
      inhibition of spontaneous proliferation of the BM-derived blast cells from 9 of
      the 14 patients and of the PB-derived cells from 10 of the 14 patients. However,
      in some of these patients, the lower IL-1ra doses (down to 100 ng/ml) induced
      potentiation of spontaneous proliferation, suggesting a novel regulatory pathway
      for IL-1 receptor engagement. Similar results were obtained on CFU-AML colony
      formation, showing inhibition at higher IL-1ra doses, but in a few AML cases
      stimulatory effect at lower IL-1ra doses.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7629565
TI  - A comparative study with two administration schedules of leucovorin and 5
      fluorouracil in advanced colorectal cancer.
AB  - One hundred and seven previously untreated patients with measurable metastatic
      colorectal cancer who were treated with 5-fluorouracil (5FU) and leucovorin (LV)
      in two different maximum doses and schedules were retrospectively analyzed. Group
      A, 52 pts, was treated with LV 200 mg/m2/D i.v. push, followed by 5FU 700 mg/m2/D
      i.v. 1 h infusion for 5 D. Cycle was repeated every 21 D. Group B, 55 pts, was
      treated with LV 500 mg/m2/D in a 2 h infusion and 5FU 600 mg/m2/D i.v. bolus at
      mid-time of LV infusion, repeated every week for 6 wk followed by 2-wk rest
      period. There was no difference in response (A 8%, B 11%). Median survival for A
      was 37 (2-131) wk, B was 59 (1-112) wk (P = 0.021), time to progression for A was
      20 (0-131) wk, B 30 (0-102) wk (P = 0.021). Administered mean dose intensity of
      LV was 350.8 mg/m2/wk in group A and 405.0 mg/m2/wk in group B without any
      significant difference; that of 5FU was significantly higher in group A as
      compared to group B (1205.3 vs 468.9 mg/m2/wk, respectively) (p < 0.0001). This
      difference was a consequence of the planned dose intensity for this drug in the
      two treatment regimens. Toxicity was more frequent and intense in group A for
      mucositis (P < 0.001), fatigue (P < 0.01), and neurotoxicity (P < 0.05), and in
      group B for neutropenia (P < 0.001) and nausea-vomiting (P < 0.001). There were
      one and four iatrogenic deaths in group A and B patients, respectively
      (NS).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7629566
TI  - Different biological conditions influencing bacterial adherence assay.
AB  - Adherence of bacteria to animal cells is considered the first step in the
      pathogenesis of many infectious diseases. The most suitable techniques developed
      in vitro to check the capacity of bacteria to adhere to different tissues use
      monolayers of established cell lines. We studied the influence of incubation time
      (1, 2, 3 hours), cell substrates (Hep-2, H-407) and the number of bacteria per
      cell (1, 10, 100, 1000) on the adherence index (number of adherent bacteria per
      cell determined by microscopic count) of the fimbriated Escherichia coli 454
      strain, Proteus rettgeri 25 and Enterobacter cloacae 10. The data were analyzed
      with different statistical methods and the results evidenced that all the
      conditions considered affect either the end-point of the test or the adherence
      index. Our observations indicate that the different methods used make it
      impracticable to compare many data from the literature and suggest the need to
      search for more homogeneity in this type of assay.

PMID- 7629568
TI  - [Cystic meningioma in children. Apropos of a case].
AB  - A case of cystic meningioma in a 9-year old girl is reported. The initial
      clinical symptom was focal epilepsy, and this was followed by progressive
      hemiparesis. CT of the brain detected a calcified tumour to which two cysts were
      attached. The tumour was strongly enhanced by the contrast medium. Histology
      confirmed that the lesion was a meningioma of the psammous type. A review of the
      literature showed that this is a rare tumour the pathogenesis of which can be
      explained in various ways. Nautal's classification into 4 types is the most
      widely adopted. The diagnosis has been made in only 38% of the 166 cases
      published.

PMID- 7629567
TI  - Carotid bifurcation stenosis: a comparative study between MR angiography and
      duplex scanning with respect to digital subtraction angiography.
AB  - PURPOSE: This study compared sensitivity, specificity and diagnostic accuracy of
      Echoduplex and Magnetic Resonance Angiography (MRA) in the evaluation of carotid
      bifurcation stenosis. MATERIAL AND METHODS: Twenty-five patients with clinical
      signs suggestive for cerebrovascular insufficiency (CVI) were studied with Duplex
      scan, MRA and Digital Subtraction angiography (DSA). Gold standard was the
      angiographic examination. RESULTS: on equal value of sensitivity (80.5%), MRA
      showed 96% specificity versus 81% of Duplex scan, 89.4% diagnostic accuracy
      versus 80.9% for Duplex scan. As for stenosis over 31%, the value of sensitivity
      did not change i.e., 80.5%; MRA showed 100% specificity versus 97.1% for Duplex,
      91.2% diagnostic accuracy versus 89.1% respectively. These values compared by the
      test for categorial analysis and correspondence analysis (p < 0.05) did not
      indicate any statistically significant difference. DISCUSSION: on the basis of
      our experience and as shown by current literature [2, 12] we can state that both
      MR-angiography and Duplex scan fail in quantifying correctly carotid stenosis
      with consequent over- and underestimation [3, 4]. However, they can be considered
      effective diagnostic procedures in a screening program [12, 16]; they are
      accurate, safe and accepted by the population. CONCLUSIONS: on the basis of the
      cost in planning the screening of a population at risk for CVI, Duplex scanning
      is still to be considered the elective procedure.

PMID- 7629569
TI  - Spinal cord ischemia diagnosed by MRI. Case report and review of the literature.
AB  - The purpose of this paper is to report a case of medullary ischemia diagnosed by
      MRI and to determine any MRI characteristics that may be useful for the diagnosis
      in the light of the published data. The patient was a 60 year-old male with
      hypertension and diabetes, referred to us for flaccid paraparesis and sphincter
      disorders of acute onset. Physical examination revealed, beside flaccid
      paraparesis, both superficial and deep hypoesthesia at L1 level and greater on
      the right. MRI showed a small area of signal hyperintensity on T2 weighted images
      and in proton density localized in the posterior part of the spinal cord at the
      level of T12 body. The patient was treated with oral antidiabetic, antiaggregant
      and antihypertensive drugs as well as neuromotor rehabilitation, and his clinical
      conditions improved; a control MRI, six months later, showed disappearance of the
      previous finding and only mild medullary atrophy at the level of the lesion.
      Medullary ischemia has been observed in a variety of pathological conditions
      (inflammatory, neoplastic, traumatic degenerative and iatrogenic), and most
      frequently involves the dorsal portion of the spinal cord. Four clinical
      pathological manifestations of medullary ischemia have been described: infarction
      from occlusion of the anterior spinal artery; "patchy" or "lacunae infarction";
      "transverse ischemic infarction"; selective ischemia in the regions of the
      posterior spinal arteries. A review of the literature yielded 61 cases of spinal
      ischemia diagnosed by MRI for a total number of 80 MRI scans, 12 of which were
      long-term controls.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7629570
TI  - [Intramedullary glioma. Postoperative MRI aspects].
AB  - MRI is the standard exploration of intramedullary tumours. Following up the
      patients is of prime importance to detect and treat possible recurrences at an
      early stage. The purpose of this paper is to specify the postoperative MRI
      semiology of intraspinal gliomas. During the 1986-1992 period, 47 patients
      operated upon in the Bicetre hospital for primary intraspinal tumours were
      followed up with high-field MR (1.5 Tesla, Signa, G.E.). The retrospective visual
      study was carried out by two neuro-radiologists. The patients' group consisted of
      24 women and 23 men aged from 15 to 67 years (mean 38 years). The tumours treated
      were 29 ependymomas and 18 astrocytomas. Eighty-five MRI examinations were
      analysed. Most of them comprised at least two planes in T1 and T2-weighted spin
      echo sequences with gadolinium injection, then only T1-weighted spin echo
      sequences after gadolinium injection (0.1 mmol/kg). The mean postoperative follow
      up period in the 47 patients was 32 months (range 7 to 84 months). Contrast
      enhancement of the spinal cord was observed in 20 cases. In the 6 patients with
      recurrence (5 astrocytomas, 1 malignant ependymoma) there was a segmental
      increase of spinal cord volume with contrast enhancement after gadolinium
      injection. In 3 out of these 6 patients clinical deterioration appeared later
      than MRI semiology. In clinically stable patients neither enhancement nor
      increase in spinal cord size was found in 27 cases, and enhancement alone was
      noted in 12 cases. There was no reliable criterion in the analysis of post
      gadolinium signal enhancement that could be used to differentiate recurrence from
      cicatricial contrast enhancement.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7629571
TI  - [Posterior epidural adipose tissue and the narrow lumbar canal: replacement
      tissue or cause of impingement?].
AB  - The role played by the epidural fat has been reported in lipomatosis induced by
      exogenous glucocorticoids and in severe obesity with lipomatosis. The role played
      by the "normal" posterior epidural fat (PEF) in lumbar canal stenosis (LCS) is
      less well known. The purpose of this study was to determine the part taken by PEF
      in LCS patients without endocrine disease, corticosteroid therapy or obesity. For
      this, we tried to specify the amount and distribution of PEF among the soft
      tissues in the vertebral canal, to demonstrate the involvement of PEF in dural
      sac compression, to describe the radiological features observed in cases of LCS
      and to look for associated morphological factors. The records of 30 LCS patients
      without exogenous or endogenous lipomatosis and in whom the essential pathogenic
      factor in 40 levels was PEF were reviewed retrospectively. At disc level, PEF was
      evaluated in the lower part of the mobile segment by means of CT or MRI axial
      sections cut through one or two spaces between L2-L3 and L4-L5. Measurements were
      made in 25 men (80%) and 6 women (20%) aged from 33 to 83 years (mean: 58 years).
      Most patients were suffering from lumbar pain, radiculopathy and/or neurogenic
      intermittent claudication. The data measured were: antero-posterior (AP) diameter
      of the dural sac, AP diameter of the bony lumbar canal (BLC), interligamentous
      distance (ILD) opposite the articular facets, and surface of PEF. The soft
      elements present on the midline--anterior epidural space (AES) and posterior
      epidural (PEF)--were expressed as percentage of the AP diameter of the bony
      lumbar canal.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7629572
TI  - Primary cerebellar and spino-cerebellar ataxia an MRI study on 63 cases.
AB  - 63 patients with primary cerebellar and spinocerebellar ataxia have been studied
      with MRI. This method allows to identify in vivo different groups of diseases
      such as that characterized by atrophy of cerebellum alone; that with atrophy of
      cerebellum associated with brainstem changes; the forms with associated changes
      of basal ganglia; the forms with spinal cord atrophy alone, as well as
      transitional forms. An interesting correlation between the varying groups and the
      type of inheritance was found, while no correlation with other clinical aspects
      was observed.

PMID- 7629573
TI  - [Hypoxic cerebral lesions. X-ray computed tomography and MRI aspects. Apropos of
      20 cases. Selective vulnerability of the striatopallidum].
AB  - Brain lesions following hypoxic-ischaemic injuries are known from autopsy
      studies, but their appearance in live patients has been only occasionally
      described, and only sporadic reports have been published on their CT and MRI
      images. Over a 2-year period (1991-93) we studied the clinical, MRI and CT
      features in 20 patients shortly after a severe hypoxia. Clinical examination
      showed motor extrapyramidal signs in 13 cases and coma in 7 cases. MR with
      inversion recovery (IR) and T2-weighted spin echo (SE) sequences was performed in
      17 patients and CT in 15. Bilateral lesions were found in 11 cases, but in 13 of
      them CT was normal. Radiological lesions were always symmetrical and bilateral,
      located in the pallidum in 10 cases, the striatum in 4 cases and the thalamus in
      2 cases. Additional white matter lesions were present in only 4 MRI examinations.
      No relationship was found between the mechanism of hypoxia and the severity of
      clinical signs. The course of the clinical signs was correlated with the presence
      of radiological lesions. In comatous patients there was a relation between
      parkinsonism and abnormalities of basal ganglia. None of the patients who had
      perinatal asphyxia had radiological lesions. The presence of pallidal or striatal
      confirmed the hypoxic origin of neurological symptoms, especially in patients
      with parkinsonism. MRI, particularly in IR sequences, makes it possible to detect
      small lesions in basal ganglia after hypoxic injuries.

PMID- 7629574
TI  - [Modern imaging in cerebral vein angioma].
AB  - Cerebral venous angiomas are vascular malformations of the brain which, before
      the advent of modern imaging, and in particular MRI, were thought to be rare.
      They have a specific angiographic aspect called "caput Meduse" as it corresponds
      to the description of a large draining vein to which converge numerous radial
      veins located in the white matter. These true vascular malformations have
      characteristic histological features making it possible to differentiate them
      from other vascular malformations, notably cavernomas. These lesions are less
      scanty than classically believed, being the most frequent malformations
      encountered in post-mortem examination series. The circumstances in which
      cerebral venous angiomas are discovered vary considerably, and haemorrhage can be
      the revealing sign. Some authors regard these malformations as "abnormalities" of
      white matter veins and not as pathological entities, since they derive from a
      change in development during embryogenesis, but this theory is not supported by
      any anatomical evidence. The same authors attribute the bleeding to an associated
      cavernoma. Whereas CT enables venous angiomas and possible associated cavernomas
      to be detected, only repeated MRI explorations performed after the finding of
      venous angioma and hemorrhage can permit, by analysis of signal changes, to
      confirm or invalidate the non-pathological theory of the venous malformation and
      its tendency to bleed. Apart from hemorrhages, since gadolinium is used MRI is
      the most reliable and least invasive means to diagnose angiomas and to detect
      associated occult angiographic malformations. For this reason, nowadays only
      hemorrhages require an angiography in search of an arteriovenous malformation
      demanding prompt treatment. Moreover, MRI makes it possible to detect
      angiographically occult malformations.

PMID- 7629575
TI  - A new era of certainty.

PMID- 7629576
TI  - Intellectual decline predicts the parietal perfusion deficit in Alzheimer's
      disease.
AB  - The pathophysiology of Alzheimer's disease may be reflected more in an
      individual's decline from premorbid levels of functioning than in current
      measures of absolute severity. To test this hypothesis, we computed an index of
      intellectual decline for individual patients and examined its relationship to
      Alzheimer's disease-related functional brain abnormalities. METHODS: We studied
      27 patients with Alzheimer's disease diagnosed by ADRDA-NINCDS criteria. We used
      patient demographics and published formulas to construct estimates of premorbid
      Wechsler Adult Intelligence Scale (WAIS-R) IQs for each subject in the sample and
      used a current IQ assessment to estimate the decline in IQ that occurred during
      the disease for each subject. Cortical perfusion was quantified by the planar
      133Xe regional cerebral blood flow (rCBF) technique. The characteristic
      abnormality in parietal cortex was expressed by the parietal index (PI). RESULTS:
      Over the estimated disease duration of 3.8 +/- 2.2 yr, the full-scaled IQ
      declined by an estimated 28.0 +/- 15.5 points. The current PI was in turn well
      correlated with the IQ decline (r = 0.66; p < 0.001). This association was linear
      and stronger than those with other, more common measures of current severity. A
      multiple stepwise regression analysis suggested that IQ decline alone accounted
      for the variance in PI related to clinical deterioration. Actual images showed a
      mild blood flow deficit in patients with the smallest estimated IQ declines but
      deep and extensive lesions in patients with large declines. CONCLUSION: These
      results suggest that the decline from the premorbid baseline, rather than current
      level of functioning, best predicts the extent of brain damage reflected in the
      rCBF abnormality, a finding independent of demographic variance.

PMID- 7629577
TI  - Clinical aerosol inhalation cine-scintigraphy to evaluate mucociliary transport
      system in diffuse panbronchiolitis.
AB  - This study evaluates the mucociliary transport system in patients with diffuse
      panbronchiolitis using aerosol inhalation cine-scintigraphy (AICS). METHODS:
      Forty-one subjects, 10 healthy controls and 31 patients with diffuse
      panbronchiolitis, were studied. In addition, the mucociliary transport system was
      evaluated in 11 patients who had received erythromycin therapy for 3-8.3 yr.
      Following inhalation of 99mTc-human serum albumin aerosol for 3-5 min in a
      sitting position, the subjects were placed on the imaging table in the supine
      position and posterior images were obtained dynamically for 20 sec/frame over 2
      hr with a gamma camera linked to a digital computer. The 360 20-sec serial frames
      were edited into a cinematographic presentation at 200-msec intervals. Clinical
      evaluation of the mucociliary transport system was based on the bolus movement of
      radioactive aerosol from the main bronchi to the trachea and the movement
      patterns, which were divided into four types using the movement in the controls
      as a standard (type I): type I, rapid and smooth movement; type II, slow
      movement; type III, stagnation at the carina; and type IV, complete stasis.
      RESULTS: All patients with diffuse panbronchiolitis had types III and IV,
      indicating that mucociliary transport system was severely impaired. Of the 11
      patients on erythromycin therapy, 8 had movement pattern type IV and 3 had
      movement pattern type III before erythromycin therapy. In eight patients (72.7%),
      movement pattern was improved to type I or II after therapy. CONCLUSION: Aerosol
      inhalation cine-scintigraphy helps evaluate the clinical usefulness of
      erythromycin therapy in diffuse panbronchiolitis.

PMID- 7629578
TI  - Effect of endoscopic variceal sclerotherapy on esophageal motor functions and
      gastroesophageal reflux.
AB  - Sclerotherapy results in significant local complications, both immediate and
      delayed. This study was designed to examine the esophageal pathophysiology
      underlying these complications. METHODS: We prospectively evaluated esophageal
      transit, motility abnormalities and gastroesophageal reflux (GER) with barium
      studies and esophageal functional scintigraphy in 24 patients (20 men, 4 women;
      mean age 33 +/- 12.4 yr) before sclerotherapy (Phase I), after two sessions
      (Phase II), following variceal eradication (Phase III) and 4 wk later (Phase IV).
      RESULTS: Varices were obliterated after 5.6 +/- 1.9 sessions of intravariceal
      sclerotherapy performed weekly with 1% polidocanol (17.3 ml per session). There
      was no baseline Phase I dysmotility or reflux. Phase II studies recorded a marked
      delay of esophageal global and segmental (mid and distal) transit time in 98.2%
      of patients by scintigraphy and 90% by barium studies. Incoordinate contractions
      and aperistalsis were observed in 0, 66.7%, 58.3% and 33.8% of patients from
      Phases I-IV studies, respectively. Barium studies revealed tertiary waves and
      reverse peristalsis in 0, 50%, and 75% of patients from Phases I-III; strictures
      were observed in 0, 1, and 3 patients during Phases I-III. GER was detected
      scintigraphically in 0, 58.3%, 25% and 16.6% during Phases I-IV sequentially. In
      contrast, barium studies grossly underestimated GER (0, 5% and 15% at phases I
      III). CONCLUSION: There was strong concordance between esophageal symptoms,
      transit, motility abnormalities and GER (p < 0.05). Variceal eradication (Phases
      III and IV) was associated with a gradual recovery of esophageal symptoms, ulcers
      and all abnormal scintigraphic parameters. Sclerosant-induced chemical
      esophagitis in association with peptic esophagitis due to gross reflux following
      sclerotherapy possibly can explain the symptoms in most patients.

PMID- 7629579
TI  - Technetium-99m-sulfur colloid SPECT imaging in infants with suspected heterotaxy
      syndrome.
AB  - For the evaluation of a variety of hepatosplenic disorders, SPECT complements
      planar 99mTc-sulfur colloid liver/spleen imaging. By isolating small, ectopic or
      poorly functioning spleen(s) from overlying or adjacent liver, SPECT imaging
      should facilitate identification of splenic tissue in infants with suspected
      heterotaxy syndrome. METHODS: During a 10-yr period, 10 planar-only and 9 planar
      plus-SPECT liver/spleen scans were obtained from 15 infants, 13 of whom were less
      than 1 mo of age at first examination. Four of the planar-only group had follow
      up planar-plus-SPECT imaging. Scintigraphic diagnosis regarding presence of
      splenic tissue was correlated with clinical diagnosis. RESULTS: Thirteen infants
      had splenic tissue; two were asplenic. Planar-only imaging provided correct
      diagnoses in six [four with, two without spleen(s)] but was negative or equivocal
      in four infants. Planar-plus-SPECT imaging was positive in all in whom it was
      performed; moreover, in 4/13 infants (31%), splenic tissue was documented only by
      SPECT imaging. CONCLUSION: Particularly when planar views are inconclusive, SPECT
      imaging is invaluable for identification and localization of functioning splenic
      tissue in infants with suspected heterotaxy syndrome.

PMID- 7629580
TI  - Thallium-201 scintigraphy in pediatric soft-tissue tumors.
AB  - Thallium-201 has been used as a tumor imaging agent in adults with lymphoma,
      brain tumors, thyroid carcinoma and bone sarcomas. The application of 201Tl in
      pediatric oncology has been very limited. METHODS: Whole-body 201Tl studies were
      incorporated into the imaging protocols of 45 children with solid soft-tissue
      tumors. Bone and 67Ga scans as well as 131I-MIBG scans for patients with
      neuroblastoma were obtained. RESULTS: Seventeen children with lymphoma, five with
      Hodgkin's disease and twelve with non-Hodgkin's lymphoma (NHL) were studied. All
      of the patients with Hodgkin's disease showed avid uptake of 201Tl and 67Ga. The
      six patients with B-cell NHL had positive 67Ga scans and four had positive 201Tl
      scans. There was variable uptake in T-cell and undifferentiated lymphoma with an
      overall sensitivity of 69% for 201Tl and 85% for 67Ga. In 14 patients with
      rhabdomyosarcoma, 10 (71%) had positive 201Tl scans and 11 (79%) had positive
      67Ga images. Gallium and thallium scans detected lesions equally. There was poor
      uptake of 201Tl in the six children with neuroblastoma. Primary tumor and
      metastases were detected more readily with the bone and MIBG scans. Three
      children with Wilms' tumor had poor or no uptake on 201Tl images, two of three
      patients with histocytosis had no significant uptake and one patient had mild
      uptake of 201Tl. One patient with primitive neuroectodermal tumor had positive
      201Tl and 67Ga images and one patient with a neurofibrosarcoma had negative 201Tl
      and 67Ga images. There was no correlation with histological types of tumor or
      disease staging. CONCLUSION: This study shows significant uptake of 201Tl in many
      pediatric solid soft-tissue tumors. Additional study is needed to determine 201Tl
      effects on treatment response and tumor viability. Also, more studies are needed
      to assess 201Tl delayed images to determine if there is more tracer concentration
      in the tumors.

PMID- 7629581
TI  - Detecting hibernated myocardium with SPECT and thallium-glucose-insulin infusion.
AB  - Because thallium kinetics, like potassium kinetics, may be affected by serum
      insulin levels, we performed two pilot studies to identify severely ischemic
      myocardium using different protocols based on the infusion of a thallium,
      insulin, potassium and glucose solution. Results were compared with those
      obtained with two currently used protocols based on rest injection or reinjection
      of 201Tl. METHODS: In the first study (Protocol 1) of 15 men with a previous
      large myocardial infarction, perfusion was evaluated by SPECT in 20 segments
      after a 30-min infusion of 201Tl (111 MBq), insulin (5 U) and potassium (10 mEq)
      in 10% glucose solution (250 ml). Imaging was repeated 30 min later and the
      results were compared with those obtained from stress and 3-hr reinjection
      images. In the second study (Protocol 2), 15 patients were evaluated randomly at
      rest and 3 hr later (rest-redistribution). On a separate day, the patients were
      then re-evaluated after infusion of 201Tl (111 MBq), potassium (10 mEq) and
      insulin (5 U) in 5% glucose (250 ml); images were obtained 90 and 180 min
      postinjection. RESULTS: In Protocol 1, radiotracer activity in segments with no
      uptake during stress was detected in 35% with the reinjection technique and 58%
      with the insulin solution protocol. In Protocol 2, 31% of segments revealed
      thallium activity after insulin infusion but not at rest or rest-redistribution.
      Serum measurements showed high insulin levels (444 +/- 138 in Protocol 1, 125 +/-
      33 mU/ml in Protocol 2), although glucose levels were not significantly altered
      (149 +/- 32 versus 71 +/- 20 mg/dl, respectively). Potassemia was not affected
      and the patients tolerated the tests satisfactorily. CONCLUSION: These results
      confirm that continuous infusion of 201Tl with a low dose of insulin in a
      glucose/potassium chloride solution is safe and may enhance cellular uptake of
      the radiotracer in severe ischemic regions, thereby improving viable myocardium
      detection.

PMID- 7629582
TI  - Detecting deep venous thrombosis with technetium-99m-labeled synthetic peptide
      P280.
AB  - Scintigraphy, using small, thrombus-avid, synthetic peptides labeled with gamma
      emitting nuclides is an innovative approach to the noninvasive detection of acute
      deep venous thrombosis (DVT). The goal of this study was to evaluate clinically
      99mTc-P280 for imaging DVT. The peptide P280 is a 26 amino acid dimer that binds
      with high affinity to the GPIIb/IIIa receptor expressed on activated platelets
      and can be labeled with 99mTc. METHODS: Scintigraphy with 99mTc-P280 (10-22 mCi)
      was performed in nine patients with clinical suspicion and diagnostic evidence of
      DVT. Planar and tomographic images of the legs, abdomen/pelvis, chest and head
      were obtained immediately, 1, 2, 4 and 24 hr after injection. RESULTS: No adverse
      effects were noted after 99mTc-P280 administration in any patient. Positive
      visualization of thrombi occurred in eight of nine cases with confirmed DVT
      within 1 hr of tracer injection. The majority of the patients had recent onset of
      DVT symptoms (less than 3 wk), while the only negative case was diagnosed 42 days
      earlier and was likely related to an accident 7 mo earlier. Thrombi-to-background
      ratios were essentially constant over the study. Technetium-99m-P280 accumulation
      was also discernible in two patients with pulmonary embolism, while in a third
      patient the radiotracer concentrated in a cerebellar hemangioblastoma.
      CONCLUSION: These human studies indicate that 99mTc-P280 is a potentially safe
      and sensitive procedure for diagnosing DVT and pulmonary embolism. It also may
      have substantial utility in monitoring active venous thrombosis.

PMID- 7629583
TI  - Comparative study of body composition by dual-energy x-ray absorptiometry.
AB  - Dual-energy x-ray absorptiometry (DEXA) is a readily available technique that has
      recently been applied to measurement of body composition. In order to validate
      this technique, results from DEXA were compared with fat-free mass (FFM) and fat
      mass (FM) measured by total body levels of potassium (TBK), nitrogen (TBN), water
      (TBW) and carbon (TBC). METHODS: A healthy population of 127 white women and 38
      black women with a body mass index of 18-30 were recruited. RESULTS: Compared
      with each of the other methods, DEXA overestimated FM and underestimated FFM. The
      slopes of the FM by DEXA versus the FM from each of the four methods were
      approximately the same, with a s.e.e. ranging from 2.4 to 3.0 units. The slopes
      of DEXA in comparison to FFM, however, ranged from 0.61 to 0.74 and were
      significantly less than unity, with a s.e.e. of 1.6 to 2.4 units. CONCLUSION:
      These findings suggest that at high values of FFM, DEXA is measuring something
      different from the FFM measured by TBW, TBN and TBK. The program for separating
      bone and soft tissue and for separating soft tissue into fat and lean at higher
      values in the DEXA method may need to be adjusted.

PMID- 7629584
TI  - Evaluation of technetium-99m-ethylenedicysteine in renal disorders and
      determination of extraction ratio.
AB  - This article evaluates the clinical usefulness of 99mTc-ethylenedicysteine (EC)
      in patients with various renal disorders. In addition, extraction ratios of 99mTc
      EC in five volunteers were also determined. METHODS: Twenty patients were
      intravenously injected with 200 MBq 99mTc-EC and 2.5 MBq [131I]orthoiodohippurate
      (OIH) simultaneously and 11 blood samples were withdrawn within 60 min. Plasma
      clearance was determined on the basis of a two-compartment model. Imaging was
      performed in the posterior projection by acquiring three sets of images.
      Extraction ratios were determined from the blood samples obtained from the renal
      vein and abdominal aorta. RESULTS: Renal clearance of 99mTc-EC was significantly
      lower than that of OIH (p = 0.0003) with good correlation (r = 0.93). Volume
      distributions of 99mTc-EC and OIH were 26584 +/- 10807 ml/1.73 m2 and 23148 +/-
      7602 ml/1.73 m2, respectively (p = 0.047). The clearance half-lives of 99mTc-EC
      and OIH were 98 +/- 54 min and 74 +/- 54 min, respectively (p = 0.049). Protein
      binding of 99mTc-EC (33 +/- 3.2%) was significantly less than that of OIH (62 +/-
      2.8%) (p < 0.0001). Red blood cell binding of 99mTc-EC was almost negligible (5.7
      +/- 4.3%). Similar extraction ratios were obtained from blood (0.68 +/- 0.08) and
      plasma (0.70 +/- 0.07) (p = 0.062). The 60-min excretion fractions were similar
      for 99mTc-EC and OIH, with values of 50% +/- 20% and 51% +/- 19%, respectively (p
      = 0.9). CONCLUSION: Technetium-99m-EC is a suitable radiopharmaceutical for
      routine renal dynamic studies. Although the biological behavior of 99mTc-EC seems
      to be different from that of OIH, their clearances demonstrate high correlation.
      Technetium-99m-EC provides excellent quality images and has high potential in the
      evaluation of quantitative renal functions.

PMID- 7629585
TI  - Penile scintigraphy for priapism in sickle cell disease.
AB  - Penile scintigraphy with [99mTc]pertechnetate/99mTc-RBCs was performed in
      patients with sickle cell disease patients who had priapism to assess the role of
      this imaging procedure in directing the clinical management of these patients.
      METHODS: Fifteen studies were performed in 13 patients who were treated according
      to a protocol not dependent on the imaging results. The scintigraphic findings of
      penile vascular perfusion (stagnant or nonstagnant patterns) were collated
      retrospectively with the form of treatment needed for relief of the condition.
      RESULTS: Four of five patients with the nonstagnant perfusion pattern responded
      to analgesics and intravenous hydration. Four of eight patients with the stagnant
      pattern did not require any aggressive interventions such as corporeal
      aspiration/irrigation, intracorporeal epinephrine or glans-cavernosa shunt.
      CONCLUSION: Whereas the nonstagnant scintigraphic finding appeared to be a
      favorable indicator for conservative treatment, the stagnant finding was
      apparently noncontributory. In addition, no correlation was found between these
      two types of scintigraphic patterns and the subsequent sexual potency of these
      patients.

PMID- 7629586
TI  - Assessment of skeletal muscle viability by PET.
AB  - We investigated the use of [18F]fluoro-2-deoxyglucose (FDG) PET scanning for
      assessment of skeletal muscle viability in patients with peripheral vascular
      disease and in patients following free-flap skeletal muscle transfer for closure
      of open wounds. METHODS: We obtained 32 FDG-PET scans from 30 patients, either at
      the time of admission for peripheral vascular disease (n = 16) or between 1 and
      15 days after surgery for skeletal muscle transfer (n = 16). Ratios between
      injured and contralateral limb FDG tracer activity uptake were correlated with
      clinical outcome at 1 mo to 3 yr follow-up. RESULTS: Viable muscle uptake ratios
      ranged from 0.47 to 7.88 (mean: 2.26 +/- 1.81; n = 26), while nonviable muscle
      uptake ratios ranged from 0.12 to 0.46 (mean: 0.27 +/- 0.12; n = 6; p < 0.02).
      After skeletal muscle transfer, two patients with viable tissue, as documented by
      PET, required amputation due to osteomyelitis, and one patient with peripheral
      vascular disease who showed viable tissue by PET required amputation 3 mo after
      the PET scan because of recurrent ulcers. CONCLUSION: FDG-PET scanning can
      determine skeletal muscle viability in patients with peripheral vascular disease
      and in patients following free-flap transfer.

PMID- 7629587
TI  - Fuzzy logic, sharp results.

PMID- 7629588
TI  - Bone pathologic correlation of multimodality imaging in Paget's disease.
AB  - The pagetic bones in the active phase of the disease with brisk lysis and
      sclerosis manifest intense tracer uptake on planar bone and SPECT images. Intense
      tracer uptake, however, can occur also in infections, dysplasias and metastases.
      Pinhole bone scintigraphy has been shown to portray specific diagnostic signs in
      a number of skeletal diseases. In an effort to identify useful bone scan signs,
      we prospectively carried out 99mTc-oxidronate pinhole bone scintigraphy of the
      skull, vertebrae, ribs, humerus, sacrum and ilium in two patients with Paget's
      disease of the bone. The pinhole bone scintigraphy findings correlated with
      radiographic, CT and MRI findings and in the vertebra with the pathological
      study. Interestingly enough, pinhole bone scintigraphy revealed intense tracer
      uptake preferentially in the bone cortex and the rim of the affected bones. Thus,
      the cranial inner table, humeral cortex and vertebral endplates and rims were the
      seats of characteristic tracer uptake, respectively creating a scintigraphic
      version of the radiographic "cotton wool" sign, "casket" sign and "picture frame"
      sign. The pagetic lesions in the sacrum and ilium also showed intense cortical
      and rim uptake. Correlation of pinhole bone scintigraphy with radiography, CT and
      MRI indicated that such cortical or rim uptake is characteristic of Paget's
      disease.

PMID- 7629589
TI  - Differentiation of infected from noninfected rapidly progressive neuropathic
      osteoarthropathy.
AB  - Differentiation of infected from noninfected rapidly progressive neuropathic
      osteoarthropathy can be difficult in a combined bone/111In-leukocyte study. We
      present two cases: one infected and one not infected. By examining the
      distribution of the 111In leukocyte activity and the change in the lesion-to
      background ratios from the 4-hr to the 24-hr image, it may be possible to
      determine if the rapidly progressive neuropathic osteoarthropathy is infected.

PMID- 7629590
TI  - Flare phenomenon in osteosarcoma after complete remission.
AB  - A patient undergoing cytostatic therapy for osteosarcoma of the right humerus had
      bone scans at 2-mo intervals. A skeletal focus of increased radiotracer
      accumulation occurred and subsequently was confirmed by CT and MRI. A necrotic
      metastasis was found during biopsy. There were no remaining viable tumor cells.
      This finding confirms the presence of the flare phenomenon in skeletal metastases
      in primary malignant bone tumors and that radionuclide imaging may fail to detect
      intramedullary foci of viable metastases in these tumors.

PMID- 7629591
TI  - Indium-111-antimyosin Fab imaging to demonstrate myocardial involvement in
      systemic lupus erythematosus.
AB  - Indium-111-antimyosin Fab imaging has been used to indicate myocardial injury.
      This report describes antimyosin accumulation in two patients with myocardial
      involvement in systemic lupus erythematosus. Both patients complained of chest
      pain, and significant stenoses of extramural coronary arteries were ruled out by
      angiography. The first patient, a 64-yr-old woman, had immunopathologic findings
      suggestive of systemic lupus. Indium-111-antimyosin Fab imaging showed myocardial
      tracer uptake. This prompted endomyocardial biopsy providing evidence of systemic
      lupus. The patient improved under immunosuppressive therapy. The second patient,
      a 47-yr-old man, had systemic lupus diagnosed by immunopathologic findings and
      skin biopsy. He had evidence of pericarditis on electrocardiography and
      echocardiography. Indium-111-antimyosin Fab imaging demonstrated additional
      myocardial involvement, which supported the initiation of immunosuppressive
      therapy. Our results suggest that 111In-antimyosin Fab imaging may provide
      valuable diagnostic information and influence patient management in systemic
      lupus erythematosus with suspected myocardial involvement.

PMID- 7629592
TI  - SPECT imaging of ischemic myocardium using a technetium-99m-nitroimidazole
      ligand.
AB  - This investigation evaluates the efficacy of a 99mTc-labeled nitroimidazole (BMS
      181321) in identifying oxygen-deprived tissue in two canine models of myocardial
      ischemia. METHODS: For both models (A and B), epicardial microvascular oxygen
      pressure (mPO2) was monitored by measuring the oxygen-dependent quenching of
      phosphorescence lifetime of Palladium mesotetra (4-carboxyphenyl) porphine. In
      Model A (beagles, n = 5), BMS-181321 was administered intravenously and a distal
      branch of the left anterior descending coronary artery (LAD) was ligated
      completely 40 sec later. Ten minutes later, the ligature was released
      establishing tissue reoxygenation. In Model B, flow through the LAD was reduced
      until the mPO2 was about 2 Torr. After bolus administration of BMS-181321 (50-60
      mCi), coronary ischemia was continued for a residence period of up to 4 hr.
      RESULTS: With Model A, SPECT reconstructions revealed a small ischemic area in
      three of five dogs, however, a transmural accumulation of the compound was
      evident in the autoradiograms from all dogs. In the two animals in which the
      defect was not observed by SPECT, the ischemic episode had nominal effects on the
      ratio of +/- dp/dt (< 4% change as compared to baseline values). In Model B,
      SPECT reconstructions showed positive images of the oxygen-deprived area within
      the mid- to apical regions of the left ventricle (n = 5). Autoradiographic
      analysis showed a transmural association with cells resulting in an ischemic-to
      nonischemic ratio of 3.5 +/- 0.4 (n = 4) for animals with similar residence
      times. CONCLUSION: The results from both models suggest that BMS-181321 provides
      a noninvasive marker of regional ischemia in the heart and that this compound may
      have clinical utility for detection of coronary artery disease.

PMID- 7629593
TI  - Species-dependent binding of copper(II) bis(thiosemicarbazone)
      radiopharmaceuticals to serum albumin.
AB  - Copper-62-labeled pyruvaldehyde bis(N4-methylthiosemicarbazonato)-copper(II) (Cu
      PTSM) is a generator-based PET radiopharmaceutical under investigation for use in
      evaluation of tissue perfusion. Despite promising results from animals, problems
      have been encountered in the use of 62Cu-PTSM to quantitate myocardial perfusion
      in humans at high flow rates, possibly due to species-dependent interactions of
      the tracer with serum albumin. METHODS: Ultrafiltration and plasma/erythrocyte
      partitioning studies were performed to assess the protein binding of 67Cu-labeled
      Cu-PTSM and six related copper(II) bis(thiosemicarbazone) complexes. RESULTS:
      These studies reveal significant interspecies variability in the strength of Cu
      PTSM binding to serum albumin, with 67Cu-PTSM binding much more strongly to human
      albumin than to dog albumin. Most of the related Cu(II)-bis(thiosemicarbazone)
      complexes examined exhibit interspecies variability of albumin binding similar to
      that observed with Cu-PTSM. Two such complexes, Cu-ETS and Cu-n-PrTS, however,
      were identified that exhibit no preferential association with human serum
      albumin. CONCLUSION: Copper-62-PTSM exhibits substantial interspecies variability
      in the strength of its binding to serum albumin, which appears to explain the
      problems encountered in using animal data to predict 62Cu-PTSM behavior in
      humans. The 62Cu-ETS and 62Cu-n-PrTS complexes may be viable alternatives to 62Cu
      PTSM for PET studies to evaluate quantitatively myocardial blood flow in humans.

PMID- 7629594
TI  - Tissue perfusion of copper-62-PTSM: relevance of studies in animal models as
      predictors of clinical radiopharmaceutical performance.

PMID- 7629595
TI  - Radiation exposure to human trachea from xenon-133 procedures.
AB  - The general dosimetry of 133Xe for human studies is well documented, but the
      resultant radiation exposure to tracheal tissue is poorly known. This organ is of
      central relevance because the tracer is primarily eliminated through exhalation.
      METHODS: We report actual 133Xe concentrations in respiratory air during
      measurement of regional cerebral blood flow (rCBF), when the tracer is
      administered both by inhalation and intravenous injection. Data were collected
      from 102 patients, with equal gender representation and an age range of 18-82 yr.
      Most of the patients had subarachnoid hemorrhage or Alzheimer's disease or were
      normal control subjects. Average administered doses were 18 +/- 4 mCi by
      inhalation and 15 +/- 3 intravenously. RESULTS: We found average respiratory
      concentrations of about 1.80 mCi/liter during a 1-min inhalation and 0.74
      mCi/liter following intravenous injection of standard doses. These activities
      drop rapidly: average respiratory concentrations during the second minute are
      0.70 mCi/liter for inhalation and 0.19 mCi/liter for intravenous injection and
      reach negligible levels thereafter. We calculate that the tracheal absorbed dose
      from 133Xe procedures is approximately 28 mrad following inhalation and about 11
      mrad following intravenous injection. These values reflect the full 11-min
      exposure, but most of the activity is only present initially. CONCLUSION: These
      values will agree with previous estimates and indicate an excellent safety
      margin.

PMID- 7629596
TI  - Parameter and index images of benzodiazepine receptor concentration in the brain.
AB  - In vivo studies of ligand-receptor interactions with PET data are based on
      different approaches that provide either quantitative results (receptor density
      and affinity) or indices that are assumed to be correlated with the receptor
      concentration. The aims of this study are to obtain parametric images of
      benzodiazepine receptor concentration and of flumazenil affinity and to study the
      validity of two receptor concentration indexes. METHODS: A three-compartment
      ligand-receptor model, [11C]flumazenil, and experimental data obtained using a
      three-injection protocol in human volunteers were used to acquire parametric
      images. The delayed activity method and the apparent distribution volume
      (estimated using a two-compartment model) were also tested and their results
      compared with those of the multi-injection approach. RESULTS: Parametric images
      of receptor density, affinity and all kinetic parameters were obtained with
      acceptable variation coefficients. A correlation between receptor density and
      apparent affinity was found (r = 0.83; p < 0.0005). The correlation between
      receptor concentration and apparent distribution volume (estimated with three-
      and two-compartment models, respectively) was accessed using both a linear (the
      usual hypothesis) and a nonlinear correlation derived from the relationship
      between the receptor density and the affinity. CONCLUSION: In spite of the
      complexity of this protocol (three injections, a 2-hr experiment, blood sampling
      and a metabolite study), we showed that the multi-injection approach is suitable
      for parametric brain imaging. By using this approach as a reference, we deduced
      that the distribution volume and delayed activity images are valid methods in the
      usual range of the benzodiazepine receptor concentrations found in the human
      brain.

PMID- 7629597
TI  - SPECT imaging of fluorine-18.
AB  - The objective of this work was to determine the potential clinical usefulness of
      SPECT to image 511-keV annihilation photons. METHODS: A triple-headed gamma
      camera equipped with ultra-high-energy collimators was used to image 18F.
      Sensitivity measurements were carried out and the FWHM and FWTM were determined
      in air and for a unit-density scattering medium. Additionally, tomographic
      phantom studies were acquired to evaluate image quality. RESULTS: The
      sensitivities of the three cameras were, for all practical purposes, identical.
      At a source-to-collimator distance of 100 mm, the FWHM and FWTM were 13 and 29
      mm, respectively. A tomographic phantom study demonstrated that spheres with a
      diameter of 20 mm were well resolved when filled with 18F activity and placed
      inside a water-filled phantom. CONCLUSION: The triple-headed SPECT camera in this
      investigation is a practical means of acquiring tomographic 18F images. The
      reconstructed slices were of sufficient quality to be of value in some clinical
      studies.

PMID- 7629598
TI  - Comparative assessment of nine scatter correction methods based on spectral
      analysis using Monte Carlo simulations.
AB  - We compared nine scatter correction methods based on spectral analysis which
      process SPECT projections. METHODS: Monte Carlo simulation was used to generate
      histories of photons emitted from a realistic 99mTc phantom. A particular
      projection was considered. Information regarding the history, location and energy
      of the photons detected in this projection was analyzed to test the assumptions
      underlying each scatter correction method. Relative and absolute quantification
      and signal-to-noise ratio were assessed for each scatter corrected image.
      RESULTS: For the simulated data, two methods do not enable activity
      quantification. Among the methods requiring some parameters to be calibrated, the
      dual-energy window method shows the best compromise between accuracy and ease of
      implementation but introduces a bias in relative quantification. In this respect,
      a triple-energy window technique is more accurate than the dual-window method. A
      factor analysis approach results in more stable quantitative accuracy (error
      approximately 10%) for a wide range of activity but requires a more sophisticated
      acquisition mode (30 energy windows). CONCLUSION: These results show that a
      scatter correction method using spectral analysis can be used to substantially
      improve accurate quantification.

PMID- 7629599
TI  - Quantitative SPECT imaging: a review and recommendations by the Focus Committee
      of the Society of Nuclear Medicine Computer and Instrumentation Council.
AB  - This article is a review of the physics principles, instrumentation and
      reconstruction methods behind SPECT imaging. Particular attention is paid to the
      mechanisms that can significantly affect the accuracy of a SPECT image. We
      describe instrumentation advances and reconstruction methods used to correct
      images to improve image quality and produce quantitative images. The clinical
      importance of improved image quality and quantitation are also reviewed.

PMID- 7629600
TI  - Thallium-201 uptake in lung cancer.

PMID- 7629602
TI  - First-pass radionuclide angiocardiography using a single-crystal gamma camera:
      are count statistics actually the limiting factor?

PMID- 7629601
TI  - An Internet-based nuclear medicine teaching file.
AB  - Teaching file cases play an important role in the training of nuclear medicine
      residents; however, film-based teaching files have limitations, such as
      difficulty in accessing cases in a department with several remote clinical sites.
      The goal of this project was to develop a digital teaching file with the
      capability for local and remote (Internet) network access, with the additional
      requirements that viewing existing cases and addition of new cases be easy and
      simple. METHODS: The teaching file software (TF-Web) utilizes applications
      developed for the World-Wide-Web in combination with locally developed programs
      for importing images, entering case information, indexing, searching, case
      selection and case editing. The time required to add cases to the TF-Web and to
      access existing cases from local and remote network sites as well as computer
      storage requirements were assessed. RESULTS: Cases entered in TF-Web may be
      viewed either with or without diagnoses and may be accessed with acceptable speed
      (2-14 sec) from both local and remote network sites. A relatively complex case
      required 1.2 megabytes of storage, with lesser storage requirements for simpler
      cases. CONCLUSION: A digital teaching file has been developed that allows easy
      access from computers located both locally and elsewhere on the Internet. Digital
      storage requirements are reasonable, and, because of the unique nature of TF-Web,
      case storage may be distributed among multiple institutions.

PMID- 7629603
TI  - Dosimetric models and S factors for radiation doses to the bladder wall in
      children receiving therapeutic iodine-131-MIBG.

PMID- 7629604
TI  - The A-bomb, 50 years later: the evolution of nuclear medicine.

PMID- 7629605
TI  - Nuclear medicine in Japan.

PMID- 7629606
TI  - Mallinckrodt Fellowship awarded to breast imaging physician.

PMID- 7629607
TI  - Smoking: high hazards in high school.
AB  - BACKGROUND: Young people in school are at an impressionable age, peer pressures
      are intense, and the probability that they will pick up a high-risk behavior,
      such as smoking, is high. The key to reduction of smoking among adults is to
      target our prevention efforts at young adults and teens. OBJECTIVE: To study the
      prevalence and trend of smoking among young adults and teens and to formulate
      guidelines on smoking reduction to guide those who counsel young people. STUDY
      DESIGN: The study design is cross sectional. METHODS: This study is based on the
      data from the Oklahoma Behavioral Risk Factor Surveillance System and the
      National Youth Risk Behavioral Surveillance System - the two systems that monitor
      the prevalence of behaviors that most influence health. RESULTS: The prevalence
      of smoking among young adults (age 18-24) in Oklahoma is high at more than 21%.
      The disturbing feature is that it is higher among young females than among young
      males. The prevalence of smoking among young adults is the highest among high
      school dropouts and is more than 38%. It is lower among high school graduates
      (about 28%) and lowest among college graduates (about 18%). The percentage of
      smoking among students who classify themselves as current smokers rises from 23%
      to 30% as the students progress from grade 9 to 12 and the percentage of frequent
      smokers increases from 8% to 16%. CONCLUSIONS: Guidelines suggested for
      counselors are: 1. Along with smoking, look for comorbid behaviors such as
      alcohol use, drug abuse, and high-risk sexual behavior. 2. Ask whether the
      student has easy access to free cigarette samples. 3. Check whether the teen is
      trying to lose weight; suggest appropriate methods for losing weight if smoking
      is being used for losing weight. 4. Target health education efforts early in a
      student's school career starting in elementary school, but concentrate especially
      at the 8th or 9th grade level to have maximum preventive impact.

PMID- 7629608
TI  - Conjoined twins.
AB  - Conjoined twins, otherwise known as Siamese twins, have fascinated physicians and
      laymen alike for centuries. The minimal diagnostic criteria for conjoined twins
      is the fusion of some portion of mononuclear or monozygotic twins.

PMID- 7629609
TI  - Neuroleptic malignant syndrome: a clinical conundrum.
AB  - The neuroleptic malignant syndrome (NMS) is a potentially fatal complication of
      antipsychotic pharmacotherapy. The incidence rate of NMS is about 2% of all
      patients receiving neuroleptics, while the overall mortality rate is in excess of
      10%. Inconsistences in the diagnostic criteria for NMS have resulted in a variety
      of presentations and precipitating factors being associated with this condition,
      which in turn has led to the reporting of contradictory research findings. This
      article summarizes the literature with respect to the diagnosis and treatment of
      neuroleptic malignant syndrome and the challenge of subsequent management of the
      psychotic patient.

PMID- 7629610
TI  - Leaders in medicine: Robert K. Endres MD.

PMID- 7629611
TI  - AZT reduces HIV transmission from infected moms to their newborns.

PMID- 7629612
TI  - Industrialized medicine...

PMID- 7629613
TI  - The responsibilities of being a delegate.

PMID- 7629614
TI  - Use of cultured mucosal grafts to cover defects caused by vestibuloplasty: an in
      vivo study.
AB  - PURPOSE: In oral and maxillofacial surgery palatal mucosal grafts are routinely
      used to cover mucosal defects caused by vestibuloplasty. However, the quantity of
      palatal mucosa is a limiting factor in more extensive operations. This study
      investigated whether autologous cultured sheets of mucosa can serve as a dressing
      for these wounds. MATERIALS AND METHODS: Punch biopsies (diameter, 4 mm) were
      taken from the hard palate of eight patients (five men, three women; mean age 43
      years). Epithelial cells were enzymatically dissociated from these tissue
      specimens and grown in vitro in the presence of a fibroblast feeder layer. Within
      3 weeks, a transplantable epithelial sheet of about 20 cm2 was obtained. The
      sheet was detached from the culture flask by enzyme treatment and fixed to a
      carrier of Vaseline (Cheeseborough Ponds Inc, Greenwich, CT) gauze. Using a split
      mouth technique, the sheet was placed on half of a mucosal defect created by
      vestibuloplasty, while the other half of the defect was covered by a conventional
      split-thickness palatal graft. Both the cultured and conventional graft were held
      in place by the patient's relined denture fixed with perimandibular sutures. One
      week postsurgery, the denture and Vaseline gauze were removed. Three months after
      vestibuloplasty, biopsy specimens of each grafted site were taken and processed
      for light and transmission electron microscopy (LM, TEM). RESULTS: Three months
      postsurgery, the grafted mucosa of both sites bore close resemblance to palatal
      mucosa. Both the cultured and split-thickness grafts were vascularized, did not
      evoke a homograft reaction, and showed a smooth graft/lip mucosal junction and
      minimal wound contraction. LM and TEM revealed that both types of grafts formed a
      fully differentiated keratinizing mucosa with a well-developed basement membrane
      and rete ridges, comparable with the histology and ultrastructure of palatal
      mucosa in situ. CONCLUSION: It was concluded from this study that cultured mucosa
      can serve as a proper dressing for mucosal defects after vestibuloplasty.

PMID- 7629615
TI  - Average blood loss and the risk of requiring perioperative blood transfusion in
      506 orthognathic surgical procedures.
AB  - PURPOSE: This study quantifies the estimated blood loss in seven groups of
      orthognathic surgical procedures and the risk of requiring perioperative blood
      transfusion, and identifies the factors relating to blood loss and need for
      transfusion. PATIENTS AND METHODS: The records of 506 consecutive patients who
      underwent various orthognathic surgical procedures under hypotensive anesthesia
      from 1987 to 1990 were analyzed retrospectively. All procedures were performed by
      the authors in the same hospital setting. Patients were placed in seven groups
      based on the operation(s) performed, including single-jaw and double-jaw
      procedures. Estimated blood loss was calculated for each group and was correlated
      with patients' sex, age, and year of surgery, and whether they autodonated blood.
      The volume of intravenous (IV) fluids given was also recorded. RESULTS: Average
      estimated blood loss for all groups was 273.23 mL. Double-jaw procedures resulted
      in more blood loss than single-jaw procedures. Men and boys had a higher average
      blood loss than women and girls, but average blood loss was not affected
      significantly by patients' age or year of surgery. Only four patients (0.8%)
      received blood transfusions, and their average estimated blood loss was 975 mL.
      The percentage of patients autodonating increased from 10.4% in 1987 to 54.9% in
      1990. There was no significant difference in the percentage of autodonators by
      surgical procedure. CONCLUSIONS: The need for blood transfusion in this study was
      extremely low. Factors contributing to this are believed to be use of hypotensive
      anesthesia; a single surgical team; and a constant surgical setting. Patients
      having double-jaw surgery are at greater risk for blood loss than those having
      single-jaw procedures, and should be so advised, along with the risks of blood
      transfusion. The authors believe that under the conditions of this study the use
      of autodonation is not necessary, with the possible exception of complex double
      jaw procedures involving small patients.

PMID- 7629616
TI  - Surgical treatment of condylar process fractures using axial anchor screw
      fixation: a preliminary follow-up study.
AB  - PURPOSE: The aim of this study was to evaluate use of the axial anchor screw
      system in the treatment of condylar process fractures. PATIENTS AND METHODS:
      Seven adult patients with displaced condylar process fractures were treated using
      axial anchor screw fixation. Indications for surgery were severe dislocation of
      the condyle and occlusal changes. Clinical and radiologic examinations were
      performed 6 weeks, 6 months, and approximately 2 years postoperatively (range, 18
      to 30 months). Clinical factors recorded were occlusion, range of mandibular
      movement, and findings on palpation of the temporomandibular joints. Ramus height
      and angulation between the mandibular ramus and the dislocated condyle were
      measured and compared with the contralateral side preoperatively and at the last
      follow-up. RESULTS: The postoperative course was uneventful in most patients. All
      were free of pain, and the occlusion and facial symmetry were normal. Radiographs
      generally showed excellent fracture reduction. Translation of the condyles on
      mouth opening was symmetrical. No signs of resorption or osteoarthrosis were
      evident in most cases. However, some patients had complications. These involved
      unsatisfactory reduction in one patient causing osteolysis at the fracture line.
      In another patient bone over the screw fractured and the condyle and the screw
      tilted in a medial direction. CONCLUSION: Treatment of condylar process fractures
      using the axial anchor screw system is ideal in certain cases. The complications
      and difficulties seen may be avoidable by appropriate patient selection and
      techniques.

PMID- 7629617
TI  - Safety and efficiency of elective tracheostomy performed in the intensive care
      unit.
AB  - PURPOSE: Because transportation of a critically ill patient to the operating room
      can be hazardous and costly, a study was undertaken to determine the safety and
      efficiency of performing a tracheostomy at bedside in the intensive care unit.
      MATERIALS AND METHODS: A 2-year retrospective study (1988 to 1990) was done of
      all tracheostomies performed (102) at bedside in the intensive care unit at
      Northwestern University Medical Center. Anesthetic, intensive care, and operative
      reports were evaluated for intraoperative and immediate (48 hours) postoperative
      anesthetic and surgical complications. RESULTS: The investigation revealed an
      average anesthetic time of 41 minutes (range, 20-75 minutes), and an average
      operative time of 29 minutes (range, 15 to 60 minutes). A perioperative morbidity
      rate of 5.5% included three anesthetic and three surgical complications, without
      mortality. CONCLUSIONS: This study confirms that tracheostomy performed in the
      intensive care unit can be a safe, economical, and time-efficient procedure.

PMID- 7629618
TI  - Functional characteristics of retrognathic patients before and after mandibular
      advancement surgery.
AB  - PURPOSE: The purpose of this investigation was to compare morphologic parameters
      and functional performance between controls and a sample of patients with
      mandibular retrognathia prior to surgical correction, and to examine how oral
      motor function adapts after treatment. PATIENTS AND METHODS: Twenty-four
      retrognathic female patients were compared with 26 female controls before and up
      to 3 years after mandibular advancement surgery. Measures of skeletal morphology,
      mandibular range of motion, maximum isometric bite force, and levels of
      electromyographic activity in the anterior and posterior temporalis and masseter
      muscles during isometric bites were made on all subjects over time. One-way
      analysis of variance was used to compare the controls, the patients before
      surgery, and the patients after surgery. RESULTS: Surgical lengthening of the
      mandible averaged 7.3 mm, bringing most skeletal measures into the normal range.
      There were no significant differences in jaw muscle mechanical advantage between
      patients and controls before surgery, but surgery significantly reduced
      mechanical advantage of the anterior temporalis and masseter muscles. Jaw
      hypomobility was apparent at 6 weeks after surgery, but returned to normal values
      within 12 to 24 months. Before surgery the patients had maximum isometric bite
      forces less than half those of controls. Bite forces steadily increased after
      surgery, approaching normal values within 2 years. Before surgery the patients'
      muscle activity levels per unit of bite force were equivalent to those of
      controls or somewhat higher. After surgery some of the patients' muscles had
      significantly lower levels of muscle activity per unit of bite force than did
      controls. CONCLUSION: The results of this study suggest that correction of
      mandibular retrognathia by mandibular advancement surgery produces some
      significant functional benefits.

PMID- 7629619
TI  - The cancer-promoting effect of N-nitrosonornicotine used in combination with a
      subcarcinogenic dose of 4-nitroquinoline-N-oxide and 7,12-dimethylbenz (A)
      anthracene.
AB  - PURPOSE: This study was conducted to determine the possible carcinogenic role of
      N-Nitrosonornicotine (NNN) when combined with subcarcinogenic doses of strong
      carcinogens dimethylbenz (a) anthracene (DMBA) and 4-nitroquinoline-N-oxide
      (4NQO) in the hamster cheek pouch. MATERIALS AND METHODS: Eighty-five Syrian
      golden hamsters were randomly divided into three main groups. Group A contained
      35 animals, 20 of which were treated with 0.1% DMBA followed by 4% NNN (A-I), 5
      with 0.1% DMBA (A-II), 5 with 4% NNN (A-III), and 5 with mineral oil alone (A
      IV). Group B contained 23 animals, 13 of which were treated with 0.5% 4NQO
      followed by 4% NNN (B-I), 5 with 0.5% 4NQO (B-II), and 5 animals with
      propyleneglycol alone (B-III). Group C contained 27 animals, 14 of which were
      treated with 0.1% DMBA followed by 4% NNN and 0.5% 4NQC (C-I), and 13 with 0.1%
      DMBA followed by 0.5% 4NQO (C-II). All animals were treated three times per week
      for 16 weeks. A total of 7 animals died during this period. RESULTS: Squamous
      cell carcinoma (SCCA) developed in eight animals (67%) in the group treated with
      all three chemicals (C-I), in four animals (33%) treated with DMBA and 4NQO (C
      II), in two animals (15%) treated with 4NQO and NNN (B-I), and in two animals
      (11%) treated with DMBA and NNN (A-I). The difference between the number of
      animals that developed carcinoma in group C-I and those in groups A-I and B-I was
      statistically significant (P < .05) and this difference reached a significant
      value when group C-I and C-II were compared (P < or = .1). There was a direct
      relationship between the number of tumors produced in animals and the number of
      different chemicals applied. CONCLUSION: The results of this study indicate that
      NNN, when combined with subcarcinogenic doses of other strong carcinogens, is a
      promoter in the development of squamous cell carcinoma and that 4NQO in 0.5%
      concentration is a stronger carcinogen than 0.1% DMBA.

PMID- 7629620
TI  - Bone formation and implant degradation of coralline porous ceramics placed in
      bone and ectopic sites.
AB  - PURPOSE: This study was undertaken to determine the resorption rate of porous
      ceramic implants. The hypothesis was that implants placed in soft tissues would
      degrade more rapidly than implants placed in bone. MATERIALS AND METHODS: To test
      this hypothesis, implants were manufactured by applying a thin coating of
      hydroxylapatite onto an interconnected, porous calcium carbonate substrate.
      Control implants were made entirely of hydroxylapatite with identical
      microstructure. Two adult dogs received a total of 56 implants placed in the
      femur, skeletal muscle, and subcutaneous tissues. After killing the animals at 4
      months, the specimens were removed, embedded in plastic, sectioned, and either
      stained for light microscopic examination or subjected to quantitative image
      analysis using a scanning electron microscope. RESULTS: Contrary to the
      hypothesis, the rate of degradation was faster for implants placed in bone than
      in soft tissue. Within the 4 months, degradation was 24% to 63% in bone,
      depending on the composition. However, it was not statistically significant in
      either intramuscular or subcutaneous tissue. A surprising observation was that
      bone ingrowth occurred in 67% of the implants placed in soft tissues. On average,
      it was 4.3% in intramuscular sites and 6.6% in subcutaneous sites. This bone was
      histologically normal in 71% of the implants containing bone. CONCLUSION: This
      study demonstrates that porous ceramic implants composed of hydroxylapatite on
      calcium carbonate will degrade more rapidly in bone defects than in soft tissue
      sites. In addition, implants with interconnected porosity and surfaces of
      hydroxylapatite will become ingrown with bone even after placement in soft
      tissues. The exact mechanisms for both of these phenomena are not understood.

PMID- 7629621
TI  - Normal cartilage structure, biochemistry, and metabolism: a review of the
      literature.
AB  - PURPOSE: To understand the possible significance of the presence of proteases,
      cytokines, growth factors, and arachidonic acid metabolites in the osteoarthritic
      temporomandibular joint (TMJ), a review of the normal physiologic processes and
      participating factors in the normal TMJ is established, based on knowledge of
      structure, biochemistry and metabolism of normal cartilage in general.

PMID- 7629622
TI  - Asymptomatic radiolucency associated with a maxillary incisor.

PMID- 7629623
TI  - Traumatic superior orbital fissure syndrome: report of case.

PMID- 7629624
TI  - Sebaceous gland hyperplasia: case report and literature review.

PMID- 7629626
TI  - Periprandial running nose following partial maxillectomy.

PMID- 7629625
TI  - Mesenchymal chondrosarcoma of the maxilla in a child.

PMID- 7629627
TI  - The use of erythropoietin in a patient having major oral and maxillofacial
      surgery and refusing blood transfusion.

PMID- 7629628
TI  - Central granular cell odontogenic tumor: a case report including light
      microscopy, immunohistochemistry, and literature review.

PMID- 7629629
TI  - Infratemporal space infection after temporomandibular arthroscopy: an unusual
      complication.

PMID- 7629630
TI  - Surgical management of basosquamous carcinoma with perineural invasion: report of
      case.

PMID- 7629631
TI  - Osteochondroma of the mandibular condyle: literature review and report of two
      atypical cases.

PMID- 7629632
TI  - Orbital compartment syndrome following orthognathic surgery.

PMID- 7629633
TI  - Transantral approach to the deeply placed, unerupted maxillary third molar.

PMID- 7629634
TI  - The final shot!!

PMID- 7629635
TI  - American Association of oral and Maxillofacial Surgeons (AAOMS) 77th annual
      meeting and scientific sessions. Toronto, Ontario, September 12-17, 1995.
      Abstracts.

PMID- 7629636
TI  - Presidential address: take ownership.

PMID- 7629637
TI  - Advanced concepts in chemotherapy drug delivery: regional therapy.
AB  - Multiple solid tumors are unresponsive to chemotherapy drug levels that are given
      by systemic administration. Regional chemotherapy administration provides a
      higher drug concentration at and/or near the tumor site, thus achieving a higher
      tumor cell kill. Intravenous therapy nurses are involved in the access of the
      multiple devices, infusion of the chemotherapy drugs, and monitoring of the
      patient for the duration of the regional therapy. This article will provide a
      review of regional chemotherapy via intraarterial, intrathecal, and
      intraperitoneal routes. Nursing management will focus on the specifics of drug
      delivery and the care of the patient receiving regional chemotherapy.

PMID- 7629640
TI  - Use of hydrochloric acid to restore patency in an occluded implantable port: a
      case report.
AB  - The use of home intravenous therapy is increasing for long-term care in patients
      with chronic illness. Long-term infusions require the use of a vascular access
      device with the potential for occlusion. Occlusions may be the result of thrombus
      formation, lipid deposits, or precipitation of drug or mineral deposits. Use of
      an algorithmic approach is necessary to assist in an organized evaluation of an
      occluded vascular access device and the selection of an appropriate pharmacologic
      agent. This case study describes the use of hydrochloric acid to restore patency
      to an occluded implantable port.

PMID- 7629639
TI  - Life-support and end-of-life questions: treatment or intervention?
AB  - Advances in medical care during the past hundred years have been phenomenal.
      Before modern times, little could be done to overcome life-threatening situations
      from injury, trauma, or disease. Most interventions were counterproductive; they
      did more harm than good. It has been during the last 30 years that medicine has
      been able to save more lives than cause death.

PMID- 7629638
TI  - Intravenous immunoglobulin therapy: indications, potential side effects, and
      treatment guidelines.
AB  - Although intravenous immunoglobulin therapy is used mainly as a replacement
      therapy in humoral immune deficiency disorders and congenital or acquired
      conditions, the indications for its use have expanded over the last decade to
      other disease states, such as autoimmune diseases and variable chronic
      inflammatory syndromes. The ability to administer large achieving rapidly
      effective serum immunoglobulin G levels under painless conditions are the main
      advantages of this form of therapy. Intravenous immunoglobulin therapy has a high
      safety record although side effects range from mild anaphylactoid reactions to
      potential life-threatening reactions. It is essential to understand the
      underlying mechanisms of these potential reactions to assure safe administration.

PMID- 7629642
TI  - CDC issues new infection control guidelines.

PMID- 7629643
TI  - [Study on middle ear ventilation using positional tympanometry--normal ear].
AB  - The middle ear is a cavity surrounded by solid bones, lined with mucosa, which
      has a gas-filled lumen. Cavernous organs such as the ear should have their own
      ventilation system under atmospheric pressure. The mechanism of ventilation in
      the middle ear has not been sufficiently clarified. Ventilation performed in the
      middle ear may be classified into two types: 1) passive ventilation via the
      Eustachian tube, required in cases of abnormal pressure and 2) unique
      physiological active ventilation of the middle ear performed under atmospheric
      pressure and not involving the Eustachian tube. The purpose of the present study
      is to prove the existence of this active ventilation under atmospheric pressure.
      The subjects were 50 normal ears and elevation of middle ear pressure in the
      lateral position (determined by positional tympanometry) was studied. The change
      in the peak level, on tympanometry, was used as an index. The results were
      continuously recorded every 12 seconds. The following results were obtained. 1.
      Middle ear pressure was elevated by changing from the sitting to the lateral
      position. Venous pressure was regarded as a causative factor in this pressure
      elevation. 2. The elevated middle ear pressure in the lateral position suggested
      gas production from mastoid cells of the middle ear. The observation that the
      middle ear pressure was stabilized with the increase in pressure, up to a level
      of 85-90 mm H2O, indicated the existence of gas leakage from the Eustachian tube
      and a mechanism for controlling gas production from the mastoid cells of the
      middle ear.

PMID- 7629641
TI  - Relationship of local i.v. complications and the method of intermittenti.v.
      access.
AB  - Infiltration, infection, phlebitis, and thrombophlebitis are considered the most
      frequent complications of i.v. therapy. The purpose of our study was to determine
      if a difference existed in incidence of complications during i.v. infusions
      depending on whether the i.v. tubing is directly connected to the infusion device
      or the tubing is connected to the latex port of an i.v. lock using a needle.
      Background information, mehtod followed, and results obtained in the study are
      discussed.

PMID- 7629644
TI  - [Caloric nystagmus in the lateral recumbent position in normal subjects--the
      possibility of a participation of velocity storage and other non-convection
      factors].
AB  - To clarify the role of central velocity storage in caloric nystagmus, 20 normal
      subjects in the lateral recumbent position underwent recording and analysis using
      ENG and an infra-red video camera in darkness. The caloric stimulus was applied
      by pouring 10 ml of water at 20 degrees C for 20 seconds into the ear canal.
      After irrigation, each subject then turned to an ear-up or an ear-down lateral
      position. Ninety-nine percent of the rapid phases of the horizontal components
      were directed to the up-side ear with no relation to the irrigated ear. Sixty-six
      percent of the vertical components showed vertical nystagmus toward the lower
      eyelid, and the remaining 34% of the vertical components showed no vertical
      nystagmus. The direction of the torsional components was from the up-side ear to
      the leg with no relation to the irrigated ear. After the first phase, the
      nystagmus was more significantly reversed in the ear-up lateral position than in
      the ear-down lateral position (p < 0.01). The maximum slow-phase velocity of the
      first phase horizontal component and the nystagmus frequency of the first phase
      horizontal and vertical components were significantly smaller in the irrigated
      ear-up lateral position than in the ear-down lateral position (p < 0.01). The
      maximum slow-phase velocity of the first phase vertical component was also
      smaller in the ear-up lateral position (p < 0.05). However, the duration of the
      first phase vertical component revealed no difference between the two positions.
      These findings indicate that factors other than endolymph convection are involved
      in the first phase horizontal and vertical components. A role for central
      velocity storage in the vertical, components was suggested. When caloric
      nystagmus was analyzed as one response, including not only the horizontal
      component but also the vertical and torsional components, the possibility of
      otolithic involvement was suggested as one of the non-convection factors.

PMID- 7629645
TI  - [Evaluation of the furosemide test using the air caloric stimulator].
AB  - Both the furosemide test, and the glycerol test have been reported as being
      effective for detection of endolymphatic hydrops. In the furosemide test, the
      caloric test is performed first, and then repeated 40 minutes after i.v.
      injection of furosemide, 20 mg. The maximum velocities of each caloric nystagmus
      are compared, so the caloric stimulus conditions must be constant. In the
      original method, the caloric test is performed by irrigation with 50 ml of water
      at 30 degrees C or 44 degrees C for 20 seconds. Since it is difficult to
      accurately maintain the water temperature at a constant level, however, we use
      the air caloric stimulator NCA-105 (ICS) for the furosemide test. By using this
      stimulator, we can always perform the caloric test under the same conditions. The
      conditions of air irrigation in 28 normal subjects were set at 37 +/- 11 degrees
      C, 61/min, and 60 seconds. These conditions were confirmed in other normal
      subjects to fairly well correspond to water irrigation (30 degrees C or 44
      degrees C, 50 ml, 20 seconds). Next we reassessed the furosemide test by using
      the air caloric stimulator in normal subjects. As a result, positive effects were
      observed in 7.4% of the normal subjects. This finding was similar to that
      reported in the literature (Futaki et al., 1971). The air caloric test is
      considered to be a more useful examination than the water caloric test because it
      is less unpleasant for the subject and easily provides the same conditions before
      and after furosemide administration.

PMID- 7629646
TI  - [Study of type I and IV collagenase activity in human thyroid diseases].
AB  - The activity of type I and IV collagenase was measured in thyroid tissue obtained
      from 6 non-diseased thyroids, 4 patients with Graves' diseases, 5 with follicular
      adenoma, 6 with papillary carcinoma and 4 with follicular carcinomas. The
      relationship between these enzyme activities and invasion or metastasis of the
      original tumors was studied. The activity of type I collagenase in papillary
      carcinomas and follicular carcinomas was higher than in non-diseased thyroids,
      Graves' disease and follicular adenoma. Carcinoma tissue with invasion beyond the
      capsule in particular had higher type I collagenase activity. Type IV collagenase
      activity in carcinoma with lymph node metastasis was higher than in non-diseased
      thyroids, Graves' disease and follicular adenoma, and especially higher than
      carcinoma without lymph node metastasis. These findings suggest that increased
      type I collagenase activity plays an important role in local invasion in thyroid
      carcinoma, and that increased type IV collagenase activity plays an important
      role in lymph node metastasis.

PMID- 7629647
TI  - [Effect of potassium channel opener, Nicorandil, on cochlear electrical
      potentials in the guinea pig].
AB  - It is commonly accepted that the endocochlear DC potential (EP) of the cochlea is
      generated by electrogenic transport of potassium ion into the scala media from
      the marginal cells of the stria vascularis. In recent years, many models of the
      marginal cell have been developed in which the EP is generated by an electrogenic
      ion transport system localized in either the basal or apical membranes of the
      marginal cell. On the other hand, Salt et al. reported that EP cannot be
      generated by the marginal cells alone but, rather, may involve passive potassium
      movement across the apical membranes of basal cells. In this study, the effect of
      Nicorandil, a potassium channel opener, on EP and cochlear microphonics (CM) were
      investigated by perfusion through the perilymphatic space of the guinea pig from
      the scala tympani to the scala vestibuli with an artificial perilymph. The
      results of several concentrations were examined. Characteristic of Nicorandil, a
      vasodilatory agent, is an increase in membrane potassium conductance due to the
      opening of plasmalemma ATP-regulated K+ channels in cardiac muscle and vascular
      smooth muscle. This effect results from the membrane hyperpolarization and
      consequent reduced opening probability of voltage-dependent Ca2+ channels. When
      the perilymphatic space was perfused with a solution containing 1 x 10(-4) M
      Nicorandil, the EP level decreased from 74.8 +/- 2.4mV to +50.0 +/- 12.8mV and
      the CM amplitude fell to 78.6% of the control. At a concentration of 5 x 10(-4)
      M, EP decreased from 77.8 +/- 4.1mV to 47.0 +/- 7.6mV and CM amplitude fell to
      16.7%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7629648
TI  - [Diagnostic and therapeutic problems in vestibular neuronitis: clinical
      implications for sudden vertigo].
AB  - We defined sudden vertigo as a sudden, unilateral peripheral vestibular
      dysfunction. The criterion for its diagnosis is a single episode of vertigo
      without cochlear and central symptoms. Among 20 patients with sudden vertigo
      there was no difference in clinical aspects between those with CP (canal paresis)
      (CP% > or = 25%) and those without CP (CP% < 25%). This suggests that sudden
      vertigo with CP is due to sudden vestibular dysfunction with predominant
      involvement of the lateral semicircular canal. Basically, vestibular neuronitis
      is considered to be due to acute unilateral neuropathy of the vestibular nerve.
      However, since we have no routine examination for evaluating vestibular nerve
      function, sudden vertigo with CP should be diagnosed as vestibular neuronitis. We
      then assessed the prognosis of sudden vertigo with CP (vestibular neuronitis).
      About two years after the onset of CP 4 of 10 patients had recovered. However,
      patients with persistent CP had a handicap in their everyday life because of the
      dizziness induced by head movements. The possibility of recovery of vestibular
      function in response to steroid therapy may improve the prognosis in vestibular
      neuronitis.

PMID- 7629650
TI  - [Area and volume relationship of temporal bone air cells].
AB  - The area and volume of the air cell system of fifty normal temporal bones were
      investigated. The area on a plain X-ray, Sonnenkalb projection, was measured by a
      planimetric method and a rectangular dimensional method by Imai in 1978. The
      volumes of the temporal bone air cells on high-resolution CT were calculated
      separately as partial volumes divided in all CT planes. The sum of the partial
      volumes was calculated as the total volume of the air cells. The relationship
      between the area and the total volume of the air cell system was analyzed
      statistically. The ratio of the partial spatial volume, e.g. the tympanic cavity
      and the apical air space, to the total volume of the temporal bone air cells was
      also calculated. The results were as follows: 1) The relationship between the two
      measurements were as follows: planimetric method, Y = 0.901X - 2.26 (r = 0.885),
      and rectangular dimensional method, Y = 0.542X - 2.57 (r = 0.876). 2) The ratio
      of the volume of the tympanic cavity to the total volume of the air cell system
      was 6.74 +/- 4.07%. The larger the total volume, the smaller the ratio. 3) The
      ratio of the apical space was 7.09 +/- 4.98%, and the larger the total volume,
      the larger the ratio.

PMID- 7629649
TI  - [Evaluation of arachidonic acid metabolites in experimental rat otitis media with
      effusion].
AB  - Leukotrienes B4, C4 (LTB4, LTC4) and prostaglandin E2 (PGE2) are arachidonic acid
      metabolites which are released from various types of cells, and are considered to
      be the mediators of inflammation because of their potent vascular permeability
      increasing activity (LTC4 and PGE2) and chemotactic activity (LTB4). In this
      study, to evaluate the involvement of arachidonic acid metabolites in otitis
      media with effusion, we measured the LTB4, LTC4 and PGE2 in rat middle ear
      effusion (MEE) by radioimmunoassay (RIA). SD rats weighing about 200g were used.
      The animals were divided into two groups, and lipopolysaccaride (LPS) or
      concanavalin A (ConA) was injected into the right middle ear cavity through the
      tympanic membrane. The left middle ear cavities were injected with 200
      microliters of phosphate balanced buffered saline (PBS) and used as controls.
      After stimulation, middle ear effusion and accumulation of inflammatory cells
      such as neutrophils, macrophages, and lymphocytes was observed in the middle ear
      cavity. In contrast, no inflammatory cells were observed in the control ears.
      Proteins exudated into the middle ear cavity after LPS or ConA injection. The
      protein content increased up to 3 days, and then decreased. Substantial amounts
      of LTs and PG were detected in experimental rat OME, although hardly and LTs or
      PG was detected in the control ears or serum. LTs levels increased up to 7 days,
      and then decreased. PGE2 levels increased up to 3 days, and decreased thereafter.
      Dexamethasone effectively suppressed protein exudation, cell accumulation and
      production of arachidonic acid metabolites in the middle ear.

PMID- 7629651
TI  - [Antineutrophil cytoplasmic antibody (C-ANCA) levels in relation to the treatment
      of Wegener's granulomatosis].
AB  - We assessed the clinical significance of cANCA in relation to the diagnosis and
      follow-up of Wegener's granulomatosis patients using NephroScholor C-ANC, the
      ELISA kit for the detection of cANCA. The NephroScholor C-ANC test for cANCA was
      revealed to be useful for the diagnosis of Wegener's granulomatosis, but slightly
      less sensitive than the indirect immunofluorescence assay using human
      neutrophils, which has been in widespread use for the detection of ANCAs. With
      NephroScholor C-ANC, the cANCA titer can be estimated conveniently and expressed
      quantitatively. When conventional immunosuppressive therapy with prednisolone and
      cyclophosphamide was applied, the patients' symptoms subsided as the cANCA titer
      decreased, and thus it also seemed useful for the follow-up of Wegener's
      granulomatosis patients. However, a rising ANCA titer during the course of the
      disease was not always correlated with the occurrence of a relapse as previously
      reported. Based on these findings, it is not recommended that treatment be
      changed immediately because of elevation of the ANCA titer alone, and it never
      seemed too late to increase immunosuppressive therapy, even after a clinical
      exacerbation was observed. Several treatments other than the conventional
      immunosuppressive therapy have often been applied for our patients, especially in
      the limited type of this disease, and these treatments, including
      sulfamethoxazole-trimethoprim alone, low-dose prednisolone alone, and
      cyclophosphamide alone, have often been useful. We conclude that the choice of
      therapy must depend on the severity or the condition of the individual patient,
      and this therapeutic policy should reduce unnecessary side effects of potentially
      toxic drugs.

PMID- 7629652
TI  - [Endoscopic endonasal surgery for postoperative maxillary cyst].
AB  - Endoscopic endonasal surgery was performed on 64 patients (69 sides) with
      postoperative maxillary cyst. We marsupialized the cyst in the inferior and/or
      middle meatus to enlarge it as much as possible. To facilitate an easier approach
      to the cyst wall in the inferior nasal meatus, some patients underwent submucous
      resection of the inferior nasal concha or inferior turbinectomy. Thirty-eight
      patients (44 sides) were followed for more than six months after surgery and a
      wide opening was confirmed in 36 (81.8%) of the 44 sides. Whether we should
      utilize an endonasal approach or a Caldwell-Luc approach depends mainly on the
      location of the medial wall of the cyst. We classified the cysts into medial,
      anterolateral and posterolateral types. Drawing a line between the anterior end
      of the inferior turbinate and the base of the lateral pterygoid process, on the
      axial plane of CT at the mid level of the inferior meatus, is the first stop. A
      medial cyst extends toward the midline across this imaginary line. A lateral cyst
      is subdivided into anterolateral and posterolateral based on the position of the
      center of cyst. The endoscopic endonasal approach resulted in excellent outcomes
      in medial and posterolateral cysts, while this approach was not found to be
      suitable for anterolateral cysts.

PMID- 7629653
TI  - [Secondary tumor of the temporal bone with internal auditory meatus involvement-
      histopathological study].
AB  - Nineteen cases of secondary tumor of the temporal bone with involvement of the
      internal auditory meatus (IAM) were studied. The cases were classified into 4
      invasion modes; direct extension from head and neck tumors (12 cases),
      hematological dissemination (3 cases), diffuse leptomeningeal carcinomatosis (3
      cases), and direct extension of tumors from the intracranium (1 case). There were
      some differences in the manner in which the tumor had spread among these 4 modes.
      In most cases involving "direct extension from head and neck tumors", the tumor
      had invaded the pyramis, and then the Eustachian tube and the middle ear. When
      the inner ear or the IAM was involved, it was directly invaded by massive tumor.
      In all cases of "hematological dissemination", metastatic tumor was found
      bilaterally, but there were some differences in the manner of invasion between
      the two sides. In "leptomeningeal carcinomatosis" and "intracranial tumor", the
      tumor had invaded the temporal bone bilaterally via the IAM. In the IAM, cochlear
      and inferior vestibular nerves were more vulnerable to tumor invasion than facial
      and superior vestibular nerves. It was suggested that there are some differences
      in vulnerability to tumor invasion between the superior and inferior vestibular
      nerves. The bottom of the IAM presented a barrier-like effect against the spread
      of tumor from the IAM to the labyrinth. In some cases, however, there was massive
      tumor invasion of the internal ear directly from the IAM. Whether denervation of
      the ganglionic neurons (spiral or vestibular) causes secondary degeneration of
      peripheral sensory endorgans remains controversial. In some cases in our series,
      degeneration of the auditory or vestibular peripheral organs might be attributed
      to denervation of neurons in the spiral or vestibular ganglia. In other cases,
      however, auditory and vestibular peripheral organs remained intact despite severe
      degeneration of ganglionic neurons.

PMID- 7629654
TI  - Liposome-encapsulated alginate: controlled hydrogel particle formation and
      release.
AB  - Large unilamellar liposomes of dipalmitoyl phosphatidylcholine have been employed
      as reaction sites for calcium alginate gelation. Encapsulation of sodium alginate
      was accomplished by extrusion of phospholipid dispersions through polycarbonate
      filter of uniform pore size followed by incubation with high concentrations of
      calcium chloride. The diffusion of calcium into the liposome interior resulted in
      alginate gelatin within the liposome. Detergent treatment of the liposomes
      resulted in solubilization of the lipid bilayer with subsequent release of the
      alginate beads which were measured by laser light scattering and electron
      microscopy. The release profiles of both the liposomes with entrapped alginate
      beads and the alginate beads (released by detergent treatment of the liposomes)
      were determined using cytochrome-c as a marker for release. The release profiles
      show a rapid release of cytochrome-c over the first 2 for both preparations with
      slower subsequent release rates for the liposomes with encapsulated alginate
      beads. The similar early profile may be due to the release of cytochrome-c from
      bound calcium alginate adsorbed to the outer leaflet of the liposome. This is
      also supported by calorimetric results which indicate a marked reduction in the
      enthalpy of the main gel to liquid crystalline phase transition of multilamellar
      and large unilamellar dispersions of the lipid. This method results in the
      fabrication of easily controlled, unimodal submicron hydrogel particles which may
      be used for controlled-release applications.

PMID- 7629655
TI  - An approach to prepare microparticles of uniform size.
AB  - A novel emulsification method which employs a glass membrane of controlled pore
      size was adopted to prepare various types of microparticles. The microparticles
      thus obtained were uniform in size and the procedure proved applicable to a wide
      variety of microencapsulation processes. Furthermore, the particle size could be
      controlled by selecting preparative conditions.

PMID- 7629656
TI  - Preparation of ethylcellulose microcapsules containing theophylline by using
      emulsion non-solvent addition method.
AB  - A new technique in which ethylcellulose microcapsules containing theophylline (a
      water-soluble drug), prepared using the O/W emulsion non-solvent addition method,
      was developed. Toluene-cyclohexane was chosen as the solvent-nonsolvent system.
      The effects of four process variables, polymer concentration, species and
      concentration of emulsifier, and core to wall ratio, on the micromeritic
      properties and release behaviour of microcapsules were investigated. The results
      indicated that theophylline can be microencapsulated with a high yield (low drug
      loss) by using the O/W emulsion non-solvent addition method with the toluene
      cyclohexane system. The particle size and drug content of the microcapsules were
      influenced by these process variables. The morphology of microcapsules was also
      affected by the core to wall ratio. The release pattern of the microcapsules was
      found to have similar properties to the release of a drug from a spherical
      homogeneous matrix. The effective diffusion coefficient increased with increasing
      core to wall ratio.

PMID- 7629657
TI  - Liposomally encapsulated diclofenac for sonophoresis induced systemic delivery.
AB  - Liposomes containing diclofenac, an anti-inflammatory agent were incorporated
      into an ointment base for topical application. The drug loaded liposomes were
      characterized for various physico-chemical attributes and drug efflux profile in
      in vitro. The systemic availability of drug from liposomes following topical
      application was evaluated in rats. The effect of sonophoresis on the drug release
      profile in vitro and systemic availability in vivo was established. The
      application of liposomal diclofenac resulted in localization of the drug at the
      site of application with slow systemic availability; however, with the
      application of ultrasound pulsed drug systemic levels could be achieved.

PMID- 7629658
TI  - Properties of multiphase microspheres of poly(D,L-lactic-co-glycolic acid)
      prepared by a potentiometric dispersion technique.
AB  - Multiphase microspheres of poly(D,L-lactic-co-glycolic acid) (PLGA) were prepared
      by a multiple emulsion potentiometric dispersion technique. Water-soluble
      compounds were dissolved in the aqueous phase (W) and emulsified in soybean oil
      (O) to form a stable emulsion. This primary emulsion was dispersed in a solution
      of PLGA and acetonitrile (O) to form a W/O/O emulsion. The W/O/O emulsion was
      then dispersed in a hardening solution of light mineral oil (O) using a
      potentiometric dispersion technique to produce microspheres of the W/O/O/O type
      with a very narrow and selective size distribution. The size of the microspheres
      was controlled by varying the internal diameter of the conductive infusion tube
      or by the variation of voltage applied to the conductive tube. Particle size
      analysis revealed a particle size distribution of 1-50 microns for microspheres
      made by this method as compared to a distribution of 50-500 microns for
      microspheres made by conventional agitation methods. Chlorpheniramine maleate was
      encapsulated with a loading efficiency of 88.9% with the potentiometric method as
      compared with a loading efficiency of 74.3% for the agitation method.

PMID- 7629659
TI  - Thermal analyser and micro FT-IR/DSC system used to determine the protective
      ability of microencapsulated squid oil.
AB  - Squid oil was microencapsulated by spray drying method. Gelatin, sodium
      caseinate, maltodextrin were contained in spray drying formulation with or
      without lecithin and microcrystalline cellulose (Avicel). The thermal stability
      of the unencapsulated and encapsulated squid oils was determined by pressure
      differential scanning calorimetry (PDSC), Fourier transform infrared (FT-IR)
      microscopic photometer with DSC system and themogravimetric analysis (TGA). The
      results indicate that the above analytical apparatus is an easy and reliable
      method to investigate the samples and that the microcapsule prepared by spray
      dried formulation with lecithin as an emulsifier and Avicel as a stabilizer
      exhibits more stable thermal stability and longer shelf-life.

PMID- 7629660
TI  - Some factors affecting the size of nylon 6-10 microcapsules prepared by
      interfacial polymerization in a high-voltage electric field.
AB  - The effect of process variables such as nozzle size, flow-rate of dispersed
      phase, inter-electrode distance, and presence of an acid acceptor and a
      thickening agent in the dispersed phase, on the production and size distribution
      of nylon 6-10 microcapsules prepared by interfacial polymerization in a high
      voltage electric field was studied. Factors which increased the intensity of the
      electrostatic forces acting upon the droplets formed, such as increasing nozzle
      diameter at constant aqueous phase flow-rate and decreasing inter-electrode
      distance, were found to decrease the capsule size while those which enhanced the
      availability of the aqueous phase monomer for the polymerization reaction, such
      as the addition of an acid acceptor and a thickening agent, resulted in an
      increase in the average size of the capsules obtained. Free flowing capsules and
      a reduction in the rate of diacid chloride hydrolysis during the process were
      also obtained with increasing concentration of the thickening agent in the
      aqueous phase.

PMID- 7629662
TI  - An in vitro release kinetic examination and comparative evaluation between
      submicron emulsion and polylactic acid nanocapsules of clofibride.
AB  - Polylactic acid nanocapsules of clofibride containing soybean oil (SO) or medium
      chain triglycerides (MCT) as the oil core were prepared. The in-vitro drug
      release kinetic profiles were determined and compared to those of a clofibride
      submicron emulsion using two different kinetic techniques: the bulk equilibrium
      reverse dialysis sac technique, and the centrifugal ultrafiltration technique.
      The former technique was shown to be inadequate for in-vitro kinetic comparison
      purposes as a result of drug diffusion limitations through the dialysis membrane.
      The latter technique yielded rapid in-vitro release profiles of clofibride from
      both emulsion and nanocapsule delivery systems under perfect sink conditions
      although a consistent lower maximum drug amount was released from the MCT
      nanocapsules as compared to the corresponding emulsion. This was attributed to
      the relatively higher aqueous solubility of MCT as compared to SO. This
      comparative study, carried out, to the best of our knowledge, for the first time,
      clearly showed that both colloidal carriers behave similarly with respect to drug
      release despite their different morphological characteristics. The kinetic
      results clearly exclude either the use of submicron emulsion or of nanocapsules
      as colloidal controlled release delivery systems for any administration route
      where perfect sink conditions should prevail.

PMID- 7629664
TI  - Anterior transposition of the inferior oblique in the treatment of unilateral
      superior oblique palsy.
AB  - Anterior transposition of the inferior oblique (ATIO), is an accepted surgical
      procedure for the treatment of primary inferior oblique overaction and
      dissociated vertical deviation. Our study was undertaken to see if ATIO could be
      useful in the treatment of preselected unilateral superior oblique palsy (SOP)
      patients. Three consecutive patients with unilateral SOP with preoperative
      primary-position hypertropia averaging 27 delta, Knapp class V, underwent ATIO.
      The results were excellent and none of these patients developed primary-position
      hypotropia. Complications of ATIO in our patients consisted of some elevation
      deficiency, elevation of the lower lid in upgaze, and reduced inferior "scleral
      show" in the surgically treated eye. We are proposing that ATIO be considered as
      a beneficial operation in unilateral SOP patients with at least 25 delta of
      preoperative primary-position hypertropia.

PMID- 7629663
TI  - Neonatal dacryocystitis associated with nasolacrimal duct cysts.
AB  - Neonatal dacryocystitis is a rare complication of congenital nasolacrimal duct
      (NLD) obstruction. Recent reports suggest that the association of neonatal
      dacryocystitis and NLD cysts may be more common than previously believed. The
      purpose of this study is to describe the nasal endoscopic findings and treatment
      of three patients with this disorder. In this prospective study, three
      consecutive patients who presented at 2 weeks of age or less with dacryocystitis
      were treated with NLD probing and rigid nasal endoscopy. All patients were found
      to have congenital NLD cysts at the time of NLD probing. The cysts were
      marsupialized under endoscopic visualization. The treatment was successful in all
      patients. Dacryocystitis in the early newborn period is commonly associated with
      NLD cysts. Nasal endoscopic marsupialization of the cysts is an effective adjunct
      to treatment of these patients.

PMID- 7629661
TI  - Properties and drug release behaviour of poly(3-hydroxybutyric acid) and various
      poly(3-hydroxybutyrate-hydroxyvalerate) copolymer microcapsules.
AB  - Microcapsules of poly(3-hydroxybutyric acid) [PHB] and its copolymers with
      hydroxyvalerate [HV] were prepared by the solvent evaporation technique and
      loaded with a model drug, 2,7-dichlorofluorescein. Microcapsules were also
      prepared from the same polymers by incorporating a polyphosphate-Ca+2 complex
      into the membrane. The morphology of the microcapsules varied by the change in
      the type of polymer used, by the introduction of drug and by the incorporation of
      the complex. Drug release behaviour, encapsulation efficiency and loading were
      all found to be influenced by the polymer type. The DSC results revealed that
      upon incorporation of valerate as the co-monomer, the crystallinity of the
      polymer decreased, leading to a material with more segmental mobility. This
      probably was the reason why the loading and encapsulation efficiency of the
      homopolymer were lower than those of the copolymers. DSC also indicated that the
      complex became an integral part of the membrane.

PMID- 7629665
TI  - Case report of medial rectus muscle adherence and sixth nerve palsy occurring
      simultaneously.

PMID- 7629666
TI  - Leber congenital amaurosis and Lhermitte-Duclos syndrome: a previously unreported
      association.

PMID- 7629667
TI  - Unusual presentation of advanced Coats' disease.
AB  - The authors report the case of a 19-month-old boy with advanced Coats' disease
      whose presenting manifestation was turbid, lipoproteinaceous fluid filling the
      anterior chamber. The possible sites of origin and routes of migration of the
      turbid fluid into the anterior chamber are discussed.

PMID- 7629668
TI  - Pseudohypopyon in acute myelogeneous leukemia.
AB  - An 11-month-old boy presented with uniocular hypopyon, elevated intraocular
      pressure, and iris nodules. A differential diagnosis of physical abuse,
      infection, retinoblastoma, juvenile xanthogranuloma, and histiocytosis X were
      considered but initial physical and laboratory investigations all had normal
      results. Three weeks following initial presentation, the child developed
      fulminant acute myelogenous leukemia. The clinical course, investigations, and
      outcome are reviewed.

PMID- 7629670
TI  - Hypopigmentation of the fundi associated with Pallister-Killian syndrome.

PMID- 7629669
TI  - Peroxisomal bifunctional enzyme complex deficiency with associated retinal
      findings.
AB  - Peroxisomal bifunctional enzyme complex deficiency is a recently recognized
      abnormality of fatty acid metabolism. We herein present the association of a
      flecked retina with peroxisomal bifunctional enzyme deficiency, a clinical
      association not previously reported. We suggest the finding of a flecked retina
      in an infant presenting with hypotonia, seizures, and failure to thrive is highly
      suggestive of this diagnosis.

PMID- 7629671
TI  - Ocular abnormalities in a patient with Rothmund-Thomson syndrome.

PMID- 7629672
TI  - Managing situations involving children with ectopia lentis.

PMID- 7629674
TI  - The predictive value of posterior pole vessels in retinopathy of prematurity.
AB  - Dilation and tortuosity of the posterior pole vessels "(plus disease)" is a sign
      of poor prognosis and may be associated with threshold or prethreshold
      retinopathy of prematurity (ROP). We have found that normal posterior pole
      vessels are a reliable marker for the absence of stage 3 ROP. One hundred thirty
      two consecutive premature infants weighing less than 1600 g at birth underwent
      ROP examinations between 32 and 40 weeks' postconceptional age. The status of the
      posterior pole vessels was compared to peripheral retinal pathology. Vascular
      findings in the posterior pole were graded 0, 1, 2, or 3, with 0 representing
      normal arterioles and venules and 3 representing plus disease. The remainder of
      the fundus examination was recorded using the international Classification of
      ROP, then converted to a severity scale based on zone and stage of ROP. For each
      infant, only one examination representing the most severe stage of ROP reached
      prior to treatment or spontaneous regression was used for data analysis. There
      was a highly significant Spearman's rank correlation (rs = 0.65) between the
      posterior pole vascular abnormalities and the severity of ROP in the retinal
      periphery. Clinically important ROP was not found in any patient with normal
      posterior pole vessels (grade 0) and stage 3 disease was usually associated with
      both venous and arterial vascular abnormalities (grades 2 or 3). When ocular
      examination of premature infants is difficult because of poor dilation of the
      pupil, hazy media, or medical instability, normal appearance of the posterior
      pole vessels can be a reassuring finding if it is necessary to postpone complete
      fundus examination in infants at risk for ROP.

PMID- 7629673
TI  - Saccadic velocity analysis in patients with divergence paralysis.
AB  - Twelve patients with clinical findings of divergence paralysis underwent
      horizontal saccadic velocity testing. Peak velocities were measured using
      digitally sampled electro-oculography during 10 degrees, 20 degrees, and 30
      degrees saccades. Results were compared with those of 12 age-matched controls.
      The peak saccadic velocities of each eye in adduction and 10 degrees abduction
      did not differ from those of age-matched controls (P > .05). The 20 degrees and
      30 degrees abducting saccades showed mildly reduced saccadic velocities when
      compared with controls (P < .05). The finding of only mildly reduced abduction
      saccadic velocities bilaterally is not consistent with bilateral lateral rectus
      palsy. The data support the hypothesis that divergence paralysis represents a
      distinct clinical entity unrelated to abducens nerve paresis and argues for the
      existence of an active divergence center. We further report the surgical results
      of five patients who were treated with strabismus surgery. A 4.0 to 6.0 mm
      bilateral lateral rectus muscle resection corrected 16 to 30 delta of esotropia
      at distance without resulting in an overcorrection at near. Bilateral lateral
      rectus muscle resection is an effective therapy for divergence paralysis.

PMID- 7629675
TI  - Retinopathy of prematurity in discordant twins.
AB  - Discordant twins may be at increased risk for retinopathy of prematurity (ROP)
      because of factors related to their unequal growth. Discordancy is defined as a
      difference of 15% or more in the birth weights of the two infants. We examined
      the data in 26 sets of discordant twins from six NICUs, including birthweight,
      gestational age, sex, and highest grade of ROP. Thirty-eight percent (10) of the
      lower birthweight infants had higher grades of ROP than their twin. Twenty-three
      percent (6) of the heavier birthweight twins had higher grades of ROP than their
      smaller siblings. Three infants reached threshold, and five were prethreshold. In
      every case, their twin siblings had mild or no ROP. Thirty-eight percent of the
      twins (10) had the same ROP outcome.

PMID- 7629676
TI  - Upper age limit for the development of amblyopia.
AB  - The medical records of 64 patients between 1 and 11 years old with known onset of
      an amblyopia-inducing condition were retrospectively reviewed to determine the
      upper age limit for the development of amblyopia. Thirty seven patients (group 1)
      developed amblyopia and 27 patients (group 2) did not. The mean patient age at
      the onset of the amblyopia-inducing condition was 41.0 months (2.90 SE) for group
      1 and 92.3 months (4.02 SE) for group 2. The difference was statistically
      significant (P = .0001). No patient developed amblyopia after 73 months of age.
      The duration of the amblyopia-inducing condition and the type of amblyopia
      inducing condition were not significantly different between the two groups. The
      age of the patient when exposed to an amblyopia-inducing condition is the most
      important determinant for the development of amblyopia. Patients 6 years or older
      with a normal visual system have a low probability of developing amblyopia
      following the onset of an amblyopia-inducing condition.

PMID- 7629677
TI  - Improvement in visual acuity in children with ectopia lentis.
AB  - The early development of vision in an eye with a dislocated lens is often poor,
      leading to disappointing postoperative results due to amblyopia. A retrospective
      review of the best corrected visual acuity of 49 eyes of 27 children with ectopia
      lentis, who were rendered aphakic either spontaneously or by lensectomy, showed a
      gradual improvement. Nineteen eyes achieved an early postoperative acuity of 6/12
      or better. Of the remaining 30 eyes, 21 were followed up for 1 or more years.
      During this period, an improvement of two or more Snellen visual acuity lines was
      noted in all but one of the eyes.

PMID- 7629678
TI  - Factors affecting treatment compliance in amblyopia.
AB  - Amblyopia is the most common form of visual disability in children. Successful
      treatment by patching depends on compliance, but evidence of factors affecting
      compliance is limited and contradictory. Because there is a well established
      relationship between social deprivation and access to health care, we
      hypothesized that social deprivation might be associated with noncompliance. Data
      from a historical cohort of 961 children from seven English orthoptic clinics
      starting treatment for amblyopia in 1983 were used to study factors affecting
      compliance with amblyopia treatment. Children were classified as noncompliant if
      they failed to attend all appointments prescribed during the first year of
      treatment. There was a significant difference in compliance between centers (P =
      .0001). Overall, children with anisometropic amblyopia were more compliant than
      those with strabismus but this varied significantly between centers. A
      relationship between social deprivation and compliance was also found (P =
      .00001). Only 41% of children from the most deprived wards were compliant
      compared with 61% in the least deprived wards. Compliance was not found to be
      related to age at starting treatment.

PMID- 7629679
TI  - Peers--the great teachers of social skills.

PMID- 7629680
TI  - Guidelines for screening, evaluating, and treating children with
      hypercholesterolemia.
AB  - Hypercholesterolemia is the most frequently identified coronary heart disease
      risk factor in childhood, with 25% or more of children in the United States
      reported to have borderline high or high levels. This article provides a summary
      of current recommendations for cholesterol screening, evaluation, treatment, and
      follow-up in the pediatric office or clinic setting. Detection and treatment of
      pediatric dyslipidemia, however, is only one component of preventive cardiology
      and should be addressed in routine well child and adolescent care along with
      major efforts to prevent cigarette smoking, obesity, inactivity, and
      hypertension.

PMID- 7629681
TI  - The nurse practitioner's role in a pediatric sleep clinic.
AB  - The assessment and management of pediatric sleep disorders frequently involves a
      multidisciplinary approach that includes many practice opportunities for the
      pediatric nurse practitioner. This article discusses the approach used in The
      Children's Sleep Clinic at The Children's Hospital of Alabama, where nurse
      practitioner involvement begins with telephone triage and progresses to
      collaborative management. Recommendations for future research include
      investigation of pediatric sleep disorders and research involving the outcome of
      nurse practitioner case management.

PMID- 7629682
TI  - Characteristics of fifth-grade children in relation to the type of after-school
      care.
AB  - Does the type of after-school care affect a fifth-grade child's self-perception,
      substance use, or school performance/attendance? Children in three types of care,
      self (n = 28), sibling (n = 20), and adult (n = 106), were recruited to address
      this question. Data were obtained via the Self-Perception Profile, self-report of
      risk-taking behavior, and school records. Self-care was significantly more
      prevalent in Caucasian (23%) and Hispanic (19%) families. No significant
      differences were found across care groups in self perception, academic
      performance, or attendance. Ten to twelve percent of children reported substance
      use in each care group, though the type of substance use differed across care
      group. These data suggest that type of after-school care is not related to
      increased risk but may be related to type of substance use.

PMID- 7629683
TI  - Transition planning in early intervention: nurse practitioner implications.
AB  - The effective transition of young children with disabilities from early
      intervention services that they receive before age 3 years to services that they
      will receive as preschoolers is an important priority. Mandates in federal law
      have created new responsibilities for professionals who provide these early
      childhood services. As part of a multidisciplinary team, pediatric nurse
      practitioners can play a key role in facilitating these transitions. This article
      describes the PRIME Transition Model, a comprehensive, research-based model that
      outlines these responsibilities and presents guidelines, transition checklists,
      timelines, and medical and legal information.

PMID- 7629684
TI  - Feeding dynamics: helping children to eat well.
AB  - Pediatric nurse practitioners are in a key position to help parents learn to
      effectively feed their children. Classic research studies, current research and
      clinical observations on feeding have identified children's capabilities,
      behaviors, and potential competencies with their eating. An appropriate feeding
      relationship supports children's developmental tasks at every age and allows them
      to eat the right amount of the proper food to achieve their genetically
      determined growth endowment. Children must, in turn, attain developmental tasks.
      In defining and managing feeding problems, the pediatric nurse practitioner may
      emphasize prevention by building positive feeding interactions, and promoting
      early detection and management as well as providing treatment for established
      problems.

PMID- 7629685
TI  - Drowning.

PMID- 7629687
TI  - Medical malpractice and liability--will this be the year of reforms?

PMID- 7629686
TI  - Infant with a pigmented rash.

PMID- 7629688
TI  - President's message: PNP involvement essential in health care reform.

PMID- 7629689
TI  - On the primary functions of melatonin in evolution: mediation of photoperiodic
      signals in a unicell, photooxidation, and scavenging of free radicals.
AB  - Melatonin is widely abundant in many eukaryotic taxa, including various animal
      phyla, angiosperms, and unicells. In the bioluminescent dinoflagellate Gonyaulax
      polyedra, melatonin is produced in concentrations sometimes exceeding those found
      in the pineal gland, exhibits a circadian rhythm with a pronounced nocturnal
      maximum, and mimics the short-day response of asexual encystment. Even more
      efficient as a cyst inducer is 5-methoxyptryptamine (5MT), which is also
      periodically formed in Gonyaulax. In this unicell, the photoperiodic signal
      transduction pathway presumably involves melatonin formation, its deacetylation
      to 5MT, 5MT-dependent transfer of protons from an acidic vacuole, and cytoplasmic
      acidification. According to this concept, we observe that cyst formation can be
      induced by various monoamine oxidase inhibitors and protonophores, that 5MT
      dramatically stimulates H(+)-dependent bioluminescence and leads to a decrease of
      cytoplasmic pH, as shown by measurements of dicyanohydroquinone fluorescence.
      Cellular components from Gonyaulax catalyze the photooxidation of melatonin. Its
      property of being easily destroyed by light in the presence of cellular catalysts
      may have been the reason that many organisms have developed mechanisms utilizing
      this indoleamine as a mediator of darkness. Photooxidative reactions of
      melatonin, as studied with crude Gonyaulax extracts and, more in detail, with
      protoporphyrin IX as a catalyst, lead to the formation of N1-acetyl-N2-formyl-5
      methoxykynuramine (AFMK) as one of the main products. Photochemical mechanisms
      involve interactions with a photooxidant cation radical leading to the formation
      of a melatonyl cation radical, which subsequently combines with a superoxide
      anion.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7629690
TI  - Structure of the pineal gland in the adult cat.
AB  - The ultrastructure of the pineal gland in the adult cat is described and compared
      with that of other mammals. Connective tissue spaces showed capillaries with
      nonfenestrated endothelia and numerous unmyelinated nerve fibers. In the proximal
      region of the gland, myelinated nerve fibers coming from the anterior commissure
      were also found. Cat pinealocytes showed a nucleus with prominent nucleoli, a
      well developed Golgi apparatus, centrioles, granular endoplasmic reticulum,
      ribosomes, abundant microtubuli and enlarged mitochondria. Pinealocytes showed
      several long processes with bulbous endings filled with clear vesicles and scarce
      "synaptic" ribbons. Pineal astrocytes and their processes were characterized by
      the presence of abundant filaments.

PMID- 7629691
TI  - Prenatal alcohol exposure and pineal response to isoproterenol, vasoactive
      intestinal polypeptide, and desmethylimipramine.
AB  - Pineals from neonatal rats born to alcohol-fed mothers had lower unstimulated
      serotonin-N-acetyltransferase activity (NAT) and responded less to isoproterenol,
      vasoactive intestinal polypeptide, or desmethylimipramine challenge than did
      pineals from pups born to normal or pair-fed mothers. Group differences
      disappeared after the first week of life. Reduced NAT activity is coincident with
      elevated glucocorticoids in these pups. In contrast to these effects of chronic
      in utero ethanol exposure, acute ethanol addition to normal adult pineals in
      organ culture enhanced ISO but not VIP stimulation of NAT activity. The results
      suggest that the neonatal pineal is more affected by ethanol-induced activation
      of the adrenocortical axis during gestation than by the direct effect of ethanol
      on membrane fluidity.

PMID- 7629692
TI  - Effects of season, temperature, and photoperiod on plasma melatonin rhythms in
      the goldfish, Carassius auratus.
AB  - Effects of season, environmental temperature, and photoperiod on plasma melatonin
      concentrations were studied in the goldfish, Carassius auratus. When goldfish
      were reared under natural conditions, melatonin levels at mid-dark exhibited
      seasonal changes, with higher levels obtained in June and September than in
      December and March. When fish were kept under light:dark (LD) cycle of 12:12 at
      5, 15, or 25 degrees C during March-April, temperature-dependent increases in
      melatonin levels at mid-dark were observed. When animals were maintained under LD
      16:8 or LD 8:16 in combination with temperature changes (5, 15, and 25 degrees C)
      during January-February, the duration of nocturnal elevation in melatonin was
      controlled by the length of the scotophase while the amplitude was influenced by
      environmental temperature. These results indicate that plasma melatonin profiles
      in the goldfish exhibit seasonal changes that are regulated by both photoperiod
      and temperature.

PMID- 7629693
TI  - Urinary 6-sulphatoxymelatonin excretion reflects pineal melatonin secretion in
      the Djungarian hamster (Phodopus sungorus).
AB  - To monitor pineal function in the Djungarian hamster (Phodopus sungorus), we
      measured the urinary excretion of the melatonin metabolite 6-sulphatoxymelatonin
      (aMT6s) at 3-hr intervals by radioimmunoassay. Hamsters maintained in either long
      photoperiod (LP, LD 16:8) or short photoperiod (SP, LD 8:16) showed marked daily
      rhythms in aMT6s excretion, with elevated levels during the dark phase. In both
      photoperiods, we found large interindividual differences, mainly in the amplitude
      of the signal. However, the amplitude as well as the duration of nocturnal aMT6s
      excretion was higher in SP than in LP. Light exposure at night (180 mW/m2, 30
      min) caused a decrease in aMT6s excretion, indicating that the pineal gland is
      the major source of urinary aMT6s. Moreover, there was a significant correlation
      between nocturnal pineal/plasma melatonin contents and 24-hr aMT6s excretion. We
      conclude that, measurements of aMT6s provide a valid and quantitative index of
      pineal melatonin synthesis in this hamster species. As an advantage in
      determining pineal melatonin contents, this approach will allow noninvasive long
      term studies of individual animals under varying environmental conditions.

PMID- 7629694
TI  - Influence of prenatal photoperiod on postnatal plasma concentrations of
      progesterone and prolactin in female red deer (Cervus elaphus) reared in constant
      equatorial photoperiod.
AB  - Prenatal photoperiod influences postnatal prolactin secretion and the timing of
      reproductive development in male red deer reared from birth in a constant
      equatorial photoperiod (12:12 light:dark). The present trial investigated whether
      a similar phenomenon occurs in female red deer. Female deer whose mothers had
      been exposed for the last 14 weeks of gestation to long (group L, 18:6
      light:dark) or short day length (group S, 6:18 light:dark) were kept from birth
      in constant equatorial day length with food available ad libitum. Both groups
      showed similar live-weight gain to 90-100 weeks of age. Blood samples taken once
      or twice weekly were analyzed for progesterone and prolactin. Progesterone
      concentrations indicated that there was no difference between the groups in the
      timing of the first incidence of ovarian (luteal) activity, which occurred at a
      normal or late age for natural puberty (67 weeks or older). Only one individual
      per group exhibited normal repeated luteal cyclicity since there was a high
      incidence of irregular or abnormal luteal function. Plasma prolactin
      concentrations at birth were higher in group L than group S (P < 0.001).
      Thereafter, although the mean and peak values did not differ significantly
      between the groups, there was a significant difference in the pattern of
      secretion; deer in group L showed significant clustering of prolactin peaks (P <
      0.01) at a mean age of 48 weeks, whereas deer in group S showed a random
      distribution of peaks. Therefore, for female red deer raised in constant
      equatorial photoperiod, prenatal long day lengths did not advance timing of
      puberty.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7629695
TI  - T-helper-2 lymphocytes as a peripheral target of melatonin.
AB  - In the past several years we demonstrated that the pineal neurohormone melatonin
      has immunoenhancing properties and can counteract the immunodepression that may
      follow acute stress, drug treatment, and viral diseases or aging. Several
      laboratories have subsequently confirmed and extended our findings. It soon
      appeared evident that T-derived cytokines constitute the main mediators of the
      immunological effect of melatonin. We have recently found a high affinity (Kd:
      346 +/- 24 pM) binding site for 125I-melatonin on T-helper-type 2 lymphocytes in
      the bone marrow. Activation of this putative melatonin receptor, with both
      physiological and pharmacological concentrations of melatonin, resulted in an
      enhanced production of interleukin-4 (IL4), which in turn acted on bone marrow
      stromal cells and induced the release of hematopoietic growth factors. This
      melatonin-cytokine cascade showed the remarkable capacity of rescuing
      hematopoietic functions in mice treated with cancer chemotherapeutic compounds
      without interfering with the anticancer action of these agents. The very low
      concentration (0.1 nM) at which melatonin is active may well reflect a
      physiological function of endogenous melatonin. The pineal gland has been, in
      fact, reported to signal the blood forming system. The evidence of IL4
      involvement is relevant to our understanding of many melatonin effects and may be
      part of a pineal-immune axis involving also Th1 cytokines. The ability of
      rescuing hematopoiesis against the toxic action of cancer chemotherapeutic
      compounds and the presence of high-affinity IL4 receptors on human tumors provide
      a further promising rationale for the clinical use of melatonin.

PMID- 7629696
TI  - Stability of melatonin in aqueous solution.
AB  - Melatonin solutions are frequently used in human, animal, and in vitro research.
      Generally, fresh solutions are prepared, for fear of instability of melatonin in
      solution. We tested the high-performance liquid chromatography (HPLC) stability
      of melatonin in aqueous solutions stored room temperature, 4 degrees C, and -70
      degrees C for up to 6 months. Solutions were prepared in a laminar flow hood
      using sterile technique, directly into sterile, pyrogen-free glass vacuum vials
      for storage. Different concentrations were tested (1.0-113.0 micrograms/ml).
      There was no loss of potency as assessed by HPLC, and the preparations remained
      sterile and pyrogen-free. We conclude that melatonin solutions may be prepared in
      batches maintained in sterile, pyrogen-free vials at 4 degrees C or at -70
      degrees C until use within 6 months. This method will save on research time used
      for preparation of fresh solutions and will reduce the number of dose validation
      tests for each new experiment.

PMID- 7629698
TI  - Clinical applications of children's temperament.

PMID- 7629697
TI  - Melatonin modulation of estrogen-regulated proteins, growth factors, and proto
      oncogenes in human breast cancer.
AB  - The growth-inhibitory actions of the pineal hormone, melatonin, on human breast
      tumor cells and the possible association between this inhibition and melatonin's
      down-regulation of the estrogen receptor (ER) expression were examined in the ER
      positive, estrogen-responsive MCF-7 human breast tumor cell line. As previously
      reported, melatonin dramatically inhibits the growth of these breast tumor cells
      and down-regulates ER levels in these cells, suggesting that the modulation of ER
      may be an important mechanism by which melatonin inhibits breast cancer cell
      growth. In the present studies, Northern blot analysis was used to examine the
      expression of estrogen-regulated transcripts known to be involved in estrogen's
      mitogenic actions. Melatonin, at a physiologic concentration (10(-9) M), rapidly,
      significantly, and, in some cases, transiently elevated the steady-state mRNA
      levels of growth stimulatory products such as TGF alpha, c-myc, and pS2, which
      are normally up-regulated in response to estrogen. Conversely, melatonin
      decreased the expression of other factors normally up-regulated by estrogen, such
      as progesterone receptor and c-fos. Significant stimulation of the expression of
      the growth-inhibitory factor TGF beta was seen with melatonin treatment,
      potentially supporting the concept that melatonin's growth-inhibitory activity is
      mediated through the breast tumor cells' estrogen-response pathway. The early
      regulation of many of these products by melatonin suggests that mechanisms more
      rapid than the down-regulation of ER are important in melatonin's modulation of
      their expression. However, the long-term modulation of these transcripts (12-48
      hr) may be heavily influenced by melatonin's down-regulation of ER expression.
      These results clearly define the need for additional in depth studies to dissect
      the cellular events leading to melatonin-induced growth inhibition in breast
      tumor cells.

PMID- 7629699
TI  - Infant temperament: implications for parenting from birth through 1 year.
AB  - Individual differences in behavioral style are seen readily in the first hours of
      life of the normal newborn. The intent of this overview is to delineate some
      specific issues of infant temperament that nurses will find beneficial in their
      endeavor to facilitate positive parent-infant relationships. Topics include a
      brief overview of infant temperament research, instruments and methods of
      measuring temperament, the relationship of temperament to postpartum depression,
      and colic. Clinical advice on day-to-day living experiences with a difficult
      infant will be offered.

PMID- 7629700
TI  - Temperament in toddlerhood.
AB  - The purpose of this article is to describe how toddler temperament can affect
      parent-child relations using a goodness-of-fit framework. Nursing considerations
      for assessing toddler temperament with families and providing parental guidance
      for managing toddlers with difficult temperament styles are discussed. Emphasis
      is placed on helping parents to understand their toddler's temperament-based
      behavior and to devise strategies that maximize compatibility between the
      toddler's temperament and parental expectations.

PMID- 7629701
TI  - Children's temperament: intervention for parents.
AB  - Using the goodness-of-fit theoretical framework, an intervention study designed
      to help parents assess and understand the implications of their child's
      temperament is described. Examples of temperament strategies designed to be
      consistent with the child's needs are included.

PMID- 7629702
TI  - The influence of temperament on development during middle childhood.
AB  - Temperament continues to influence the development of children during their
      school-age years. No longer influenced primarily by their parents, school-age
      children interact with teachers and peers in situations that contribute toward
      goodness or poorness of fit.

PMID- 7629703
TI  - Children with disabilities.
AB  - The purpose of this article is to provide the clinician with a comprehensive
      review of the influence of temperament on the social and cognitive development of
      children with disabilities. Research concerning the interaction of temperament
      and cognition and the temperament characteristics of children with disabilities
      is reviewed. Also discussed are issues relevant to clinical practice, including
      assessment of temperament characteristics and interventions with parents.

PMID- 7629704
TI  - Temperament and the hospitalized child.
AB  - There is increasing evidence to support that temperament is an important variable
      in considering approaches to nursing care for the hospitalized child. Nursing
      admission assessment can be expanded to include temperament data from parent
      interviews. A number of case studies are highlighted to illustrate the
      relationship between temperament assessment, nursing interventions, and expected
      outcomes. It is recommended that pediatric nurses incorporate temperament
      information in all steps of the nursing process.

PMID- 7629705
TI  - A comparison of temperament and maternal bother in infants with and without
      colic.
AB  - This descriptive, retrospective study compared the temperament styles of 25 4- to
      8-month-old infants who had colic with the temperament styles of 30 infants of
      similar age without colic. Infant temperament style was characterized by the
      mother's ratings of her infant's behavioral style. The degree of bother that the
      mother experienced in relationship to her infant's temperament also was examined.
      Results indicated that mothers of infants with colic rated their infants'
      temperaments differently than mothers of infants without colic in the temperament
      dimensions of activity and mood. Mothers of infants with colic were more bothered
      by the infants' temperament dimension of mood than were mothers of infants
      without colic. More infants in the colic group were characterized as difficult
      than were infants in the noncolic group. Individual temperament characteristics
      should be considered in the differential diagnosis of primary excessive crying
      (colic) during the newborn and infant periods.

PMID- 7629706
TI  - Who is the "family" in family research?

PMID- 7629707
TI  - Independent plenary prescriptive authority.

PMID- 7629708
TI  - Point-of-care technology: the i-STAT system for bedside blood analysis.

PMID- 7629709
TI  - Clinical research: education needs of patients, families, and nursing staff.

PMID- 7629710
TI  - Childhood diarrhea and malnutrition in Pakistan, Part II: Treatment and
      management.

PMID- 7629711
TI  - Cameo of caring: John.

PMID- 7629712
TI  - Cameo of caring: Mama.

PMID- 7629713
TI  - Catastrophic interlude: a hard way to learn life's lessons.

PMID- 7629715
TI  - Spiritual competence: a model for psychiatric care.

PMID- 7629714
TI  - Toward a theology of nursing.

PMID- 7629716
TI  - My dream: nursing as ministry.

PMID- 7629717
TI  - The truth about caring.

PMID- 7629719
TI  - What I learned by not being hired.

PMID- 7629718
TI  - The irrepressible Mrs. Vaughn.

PMID- 7629720
TI  - Beyond appearances: caring in the land of the living dead.

PMID- 7629721
TI  - Sunday morning.

PMID- 7629722
TI  - What is caring?

PMID- 7629723
TI  - Cameo of caring: Martha.

PMID- 7629724
TI  - Cameo of caring: George.

PMID- 7629725
TI  - Effects of dimethyl sulfoxide, glycerol, and ethylene glycol on secondary
      structures of cytochrome c and lysozyme as observed by infrared spectroscopy.
AB  - Effects of 10-30% (v/v) of dimethyl sulfoxide, glycerol, and ethylene glycol on
      the H-O-H bending vibration of water and the amide I bands of horse heart
      cytochrome c and chicken egg white lysozyme in 25 mM sodium phosphate buffer (pH
      7.4) were examined at 20 degrees C by Fourier transform infrared spectroscopy.
      The H-O-H bending mode of water was strongly affected by these cryoprotectant
      solvents. Increasing the concentration of cryosolvents from 0 to 30% shifts the
      water bending band maximum from 1645 to about 1650 cm-1. Second-derivative
      analysis reveals significant changes in conformation-sensitive amide I regions of
      lysozyme ascribed to alpha-helix (1657 cm-1), turn (1674 cm-1), and unordered
      (1646 cm-1) structures; each cryosolvent increases the intensity of the 1657 cm-1
      band at the expense of bands at 1674 and 1646 cm-1. No changes in spectra deemed
      significant were observed for cytochrome c under the same conditions. There is no
      spectral evidence of structural randomization of proteins due to the presence of
      these cryosolvents. Cryosolvent-induced changes in secondary structure of
      proteins may result from changes in water structure which, in turn, perturb the
      structure of the protein and/or from direct interactions between cryosolvent and
      protein.

PMID- 7629726
TI  - Oxime derivatives of the intermediary oncostatic metabolites of cyclophosphamide
      and ifosfamide: synthesis and deuterium labeling for applications to metabolite
      quantification.
AB  - There is ongoing interest in the selective, quantitative analysis of the
      cyclophosphamide metabolites 4-hydroxycyclophosphamide (2a) and aldophosphamide
      (3a) because these tautomers are generally believed to play a key role in
      oncostatic selectivity and metabolite transport. O-(2,3,4,5,6
      Pentafluorobenzyl)hydroxylamine (C6F5CH2ONH2, 1 equiv) provided for the complete
      conversion (by 31P NMR, 60% reaction within 15 min at 20 degrees C) of 2a/3a (17
      mM in H2O/CH3OH) to E/Z-aldophosphamide O-(2,3,4,5,6-pentafluorobenzyl)oxime
      [C6F5CH2ON = CHCH2CH2OP-(O)(NH2)N(CH2CH2Cl)2; E:Z = 54:46 (+/- 3% average
      deviation)]. Under these conditions, the oxime exhibited little (6%)
      decomposition over 3 weeks. Parallel studies showed that 4
      hydroxyifosfamide/aldoifosfamide reacted completely to give the analogous
      aldoifosfamide oxime [C6F5CH2ON = CHCH2CH2OP(O)(NHCH2CH2Cl)2; E:Z = 52:48 (+/- 1%
      average deviation)] with 50% reaction within 15 min at 20 degrees C with no
      product decomposition over 3 weeks. In aqueous methanol and with 2 equiv
      C6F5CH2ONH2, clinically useful 4-hydroperoxycyclophosphamide (10 mM; tau 1/2 = 10
      min, 37 degrees C) and its isomer 4-hydroperoxyifosfamide (10 mM; tau 1/2 = 25
      min, 20 degrees C) underwent complete conversion to the corresponding aldehyde
      oximes. Each oxime was synthesized with deuterium in the chloroethyl moieties for
      use as internal standards in GC/MS applications.

PMID- 7629727
TI  - Preparation and characterization of fibrinogen-coated, reversibly adhesive,
      lecithin/cholesterol vesicles.
AB  - We have developed a method for producing fibrinogen-coated, reversibly adhesive,
      lecithin/cholesterol vesicles. In this method, fibrinogen, which is acylated in
      the presence of preformed vesicles, spontaneously incorporates into vesicular
      membranes. The degree of incorporation is a function of the extent of acylation
      of the protein. Fibrinogen-coated vesicles aggregate in the presence of thrombin,
      a consequence of intervesicular fibrin formation. The rate and extent of thrombin
      initiated aggregation depend on the fibrinogen surface concentration. Once
      aggregated, fibrin-coated vesicles can be dissociated by plasmin and by agents
      that disrupt intervesicular fibrin dimerization such as heparin and the
      tetrapeptide Gly-Pro-Arg-Pro. Fibrinogen-coated vesicles can be made to bind
      avidly to the surface of solution phase fibrin matrices and can be incorporated
      into solution phase fibrin clots. Fibrinogen-coated vesicles also bind to
      activated platelets. We propose that fibrinogen-coated vesicles will have
      practical applications as biomimetic hemostatic agents and as vehicles for the
      fibrin-specific targeting of drugs and other molecules.

PMID- 7629728
TI  - An in vivo model for screening peptidomimetic inhibitors of gelatinase A.
AB  - Gelatinase A, a matrix metalloproteinase, is frequently associated with human
      solid tumors, and its secretion and activation in the tumor milieu is considered
      important in the process of angiogenesis, invasion, and metastasis. Consequently,
      metalloproteinase inhibitors may be of value in the therapy of cancer as well as
      other disease states involving tissue remodeling and release of biologically
      active peptide/protein by proteolytic cleavage. Here we describe the development
      of a rapid screening assay for in vivo activity of peptidomimetic inhibitors of
      gelatinase A that involves assessment of inhibition of an enzyme-substrate
      reaction in a circumscribed body compartment, the mouse pleural cavity. As
      examples of the utility of this assay, in vivo activity of the aryl sulfonamide,
      sulfamyl urea, morpholino and carboxylic acid functionality at the P3' position
      of a series of hydroxamic acid inhibitors was examined after administration both
      intraperitoneally (ip) (to approximate systemic administration) and orally. For
      up to 2 h after ip administration, all inhibitors tested showed marked activity
      (> 90% inhibition) at 17 mumol/kg (approximately 10 mg/kg). This activity
      declined in a dose-responsive manner to insignificant levels at 0.67 mumol/kg
      (approximately 0.4 mg/kg). Aryl sulfonamides showed significant inhibition (>
      50%) for up to 7 h after administration. A higher dosage (136 mumol/kg,
      approximately 80 mg/kg) was required to reveal oral activity, which was observed
      only with morpholino compounds (> 50% inhibition). Thus, the model described may
      be of value in the identification of orally active gelatinase A inhibitors.

PMID- 7629729
TI  - Enhancement of calcium transport in the Caco-2 cell monolayer model.
AB  - The overall objective of this research was to identify enhancers of calcium
      transport using an in-vitro Caco-2 cell monolayer model. The enhancers studied
      were medium-chain triglycerides (MCT) and acylcarnitines (AC). The extent of cell
      damage associated with the use of these enhancers was determined by monitoring
      the release of cellular lactate dehydrogenase (LDH). The effect of chain-length
      and concentration dependence of these agents on enhancement were also determined.
      The effects of ACs were found to be superior to those of MCTs. However, the ACs
      elicited a greater release of LDH than the MCTs. The possible mechanisms of
      enhancer-mediated increase in calcium transport and the potential significance of
      this study with regard to the prevention of osteoporosis are discussed.

PMID- 7629730
TI  - Infrared spectroscopic studies of lyophilization- and temperature-induced protein
      aggregation.
AB  - Recent studies have clearly demonstrated that Fourier transform IR spectroscopy
      can be a powerful tool for the study of protein stabilization during freeze
      drying and for optimizing approaches to prevent lyophilization-induced protein
      aggregation. The purpose of the current review is to provide an overview of these
      topics, as well as an introduction to the study of protein secondary structure
      with IR spectroscopy. We will start with a general summary of the theories and
      practices for processing and interpreting protein IR spectra. We will then review
      the current literature on the use of IR spectroscopy to study protein structure
      and the effects of stabilizers during lyophilization. Next we will concentrate
      specifically on protein aggregation. The bulk of the research and the key
      assignments of spectral features in protein aggregates come from studies of the
      effects of high and low temperature on proteins. Therefore, we will first
      consider this topic. Finally, we will summarize the recent theoretical and
      applied work on lyophilization-induced aggregation.

PMID- 7629731
TI  - Significant effects of application site and occlusion on the pharmacokinetics of
      cutaneous penetration and biotransformation of parathion in vivo in swine.
AB  - Increasing attention has been paid to the variables of application site and
      dosing method in quantitation of chemical percutaneous absorption. Following
      topical and intravenous application of [ring-U-14C]parathion (PA) in weanling
      pigs, we have determined, in a previous publication, the profiles of 14C and HPLC
      separated paraoxon (PO), p-nitrophenol (PNP), and p-nitrophenyl beta-D
      glucuronide (PNP-G) in plasma, urine, tissues, and dosing device. The purpose of
      the present paper was to analyze these data further, focusing on a quantitation
      of the effects of application site (back versus abdomen) and dosing method
      (occluded versus nonoccluded) on in vivo disposition of both the parent PA and
      its sequential metabolites PO, PNP, and PNP-G. Cutaneous and systemic disposition
      parameters were determined using a numerical simulation modeling approach and
      moments analysis. Mean systemic bioavailability values of 8.9-9.2% for abdomen
      and 14.7-19.7% for back were determined. Under different dosing conditions, 1-35%
      of the topical dose was metabolized dermally, and 9-19% systemically.
      Radioactivity in plasma and urine was predominantly contributed by PNP-G and PNP.
      Site differences in 14C percutaneous absorption were governed by the differences
      in transport of PA, PO, and PNP from epidermis into blood, by local tissue
      distribution, and by the cutaneous metabolism to PNP. Systemic bioavailability of
      PA was higher from the back than from the abdomen. Occlusion not only increased
      the amount of 14C absorption and shortened the mean residence time in most
      compartments but also altered the systemic versus cutaneous biotransformation
      pattern.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7629732
TI  - Determination of vitamin A, vitamin E, and their esters in tablet preparations
      using supercritical fluid extraction and HPLC.
AB  - A rapid and precise method for the isolation of vitamins A and E and their
      acetate or palmitate esters from table matrices was developed using supercritical
      fluid extraction (SFE). The vitamins were analyzed by nonaqueous reversed-phase
      high-performance liquid chromatography after a 15-min extraction of the dosage
      form with supercritical carbon dioxide at 40 degrees C and at a pressure of 250
      atm. A quantitative comparison of SFE with an established liquid extraction
      procedure was performed on commercial tablet formulations. Vitamin recoveries of
      over 95.6% compared with conventional liquid extraction were achieved by the SFE
      technique with a much shorter sample preparation time (15 min vs 2h). Moreover,
      the automated SFE process minimized the number of sample handling operations,
      drastically reduced the consumption of harmful solvents, and provided mild
      extraction conditions for the analysis of the labile vitamins. The described SFE
      method is suitable for quality control analyses of pharmaceutical tablets.

PMID- 7629733
TI  - Effect of salts on the structure of a potent analog of growth hormone releasing
      hormone as determined by optical spectroscopy.
AB  - Optical spectroscopic methods (circular dichroism, analytical
      ultracentrifugation, and static light scattering) were employed to study the
      solution behavior of an N-terminal-acylated 76-residue analog of growth hormone
      releasing hormone (GHRH). The GHRH analog had a 30% helical configuration in
      aqueous acidic solution, unlike other GHRH analogs that had a random coil
      configuration in aqueous solutions, and self-associated. High concentrations (7
      M) of urea were required to obtain monomeric peptide, but such urea
      concentrations unfolded the peptide. Therefore, the folding and self-association
      were related events. The self-association and helix content were increased by the
      addition of various cations (e.g., Na+, Ca2+). In 7 M urea, when these cations
      were added, the peptide started to refold toward its aqueous conformation in a pH
      dependent manner; at low pH (2.5-3.5) the peptide folded to approximately 50% of
      the native configuration. At neutral pH (> 6) only small changes were seen when
      salts were added. When CaCl2 was added to a solution containing 7 M urea at pH
      2.5, the self-association of the peptide increased with the concentration of
      CaCl2. Therefore, the salt dependent self-association observed in aqueous
      solvents was present in 7 M urea. Residues 45-76 in this GHRH analog, which are
      not present outside the hypothalamus, are probably needed to interact with a
      folding chaperone in vivo and provide stability for successful membrane transport
      and maintenance of biological activity.

PMID- 7629734
TI  - Programmable drug release of highly water-soluble pentoxifylline from dry-coated
      wax matrix tablets.
AB  - The programmable release of pentoxifylline from a dry-coated wax matrix tablet
      containing behenic acid as wax matrix was investigated at 37 degrees C in
      Japanese Pharmacopeia XII 1st (pH 1.2) and 2nd (pH 6.8) fluids. The dry-coated
      tablet consisted of a low drug concentration (33% w/w) in the outer layer tablet
      and a high concentration (50-67% w/w) in the core. The drug release from the wax
      matrix significantly increased after penetrating the core; therefore, the drug
      release profiles showed specific biphasic curves. Because the contact angle of
      the wax matrix tablet increased with a decrease in the drug concentration, the
      fluid penetration in wax matrix tablet increased with an increase of the drug
      concentration. The time required for 75% drug release (T75) decreased with an
      increasing drug concentration in the core, and the T75 at pH 6.8 was slightly
      longer than that in pH 1.2. The larger core tablet had a shorter T75, indicating
      that the drug release rate was controlled by regulating the drug concentration
      and/or the weight of the core tablet.

PMID- 7629735
TI  - Pentamidine congeners. 3. Crystal structure and molecular modeling studies of
      trans-1,4-bis(4-amidinophenoxy)-2-butene.
AB  - X-ray diffraction was used to confirm the geometry of trans-1,4-bis(4
      amidinophenoxy)-2-butene dihydrochloride dihydrate (trans-butenamidine). trans
      Butenamidine is a semirigid analogue of pentamidine that has demonstrated good
      anti-Pneumocystis carinii activity in rats. Molecular modeling studies revealed
      that unlike pentamidine or propamidine, trans-butenamidine does not discriminate
      between AT and TA sequences in its binding to the minor groove of DNA. Crystal
      data: [C18H22N4O2(2+)][Cl(-)]2[H2O]2, triclinic space group, P1, a = 9.443(1) A,
      b = 11.400(1) A, c = 11.919(1) A, alpha = 62.19(1) degree, beta = 81.10(1)
      degree, gamma = 72.19(1) degree, V = 1080.3(3) A3, Z = 2, R = 0.054 for 1149
      observed reflections with I > 3 sigma (1).

PMID- 7629736
TI  - Disposition of positively charged Bowman-Birk protease inhibitor conjugates in
      mice: influence of protein conjugate charge density and size on lung targeting.
AB  - The influence of conjugate charge density and size on the targeting of cationic
      Bowman-Birk inhibitor (BBI) conjugates to the lungs was studied in mice. The
      biodistribution of BBI, either as the native protein or in the conjugated form
      (conjugated to a dicationic, tetracationic, or polycationic carrier), indicated
      that by increasing the charge density of BBI conjugates, the lung accumulation of
      the conjugates administered intravenously (i.v.) can be increased. The order of
      lung accumulation in these studies was as follows: polycationic- > tetracationic-
      > dicationic-conjugated BBI > BBI. The influence of conjugate size on lung
      accumulation was studied in three experiments. First, the biodistribution of
      poly(D-lysine) carriers of equal charge density but different molecular weight
      demonstrated that lung accumulation of polycationic carriers increases with an
      increase in carrier size. Second, the biodistributions of BBI, tyramine
      derivatized poly(D-lysine)3 kDa, and poly(D-lysine)3 kDa conjugated to BBI
      indicated that an increase in conjugate size alone is not sufficient to promote
      the lung accumulation of cationic BBI conjugates. Finally, the biodistribution
      poly(D-lysine) complexed with heparin showed that targeting of a conjugate to the
      lungs can be abolished by neutralizing the charge on the carrier. Collectively,
      data in this paper demonstrate that the carrier-mediated targeting of BBI to the
      lungs is dependent on (a) cationization of BBI, (b) the conjugate positive charge
      density, and (c) the size of the cationic conjugate if the charge density is
      maintained. Also, the data show the size of the conjugate alone does not make a
      significant impact on lung accumulation.

PMID- 7629737
TI  - Synthesis and biological activities of some 3,6-disubstituted thiazolo[3,2
      b][1,2,4]triazoles.
AB  - Some new 2,3-dihydro-3-hydroxy-6-phenyl-3-(4-substituted- (phenylthiazolo[3,2
      b][1,2,4]triazole derivatives were synthesized as antifungal agents. After their
      structures were confirmed by microanalysis and IR and NMR spectral analysis,
      their antifungal activities against Candida albicans, Candida parapsilosis,
      Candida stellatoidea, and Candida pseudotropicalis were investigated. Contrary to
      our expectations, all proved to have poor antifungal activities. Because 2,4
      dihydro-3H-1,2,4-triazol-3-ones are a new class of anticonvulsant agents, a
      series of thiazolo[3,2-b][1,2,4]triazoles was evaluated for anticonvulsant
      activity and observed as potential anticonvulsant candidates. All compounds
      examined exhibited activity against both maximal electroshock and pentylene
      tetrazole-induced seizures in mice.

PMID- 7629738
TI  - Preparation and structure of a water-in-oil cream containing lipid nanoparticles.
AB  - To obtain a topical dermatological product with a high degree of occlusivity
      combined with attractive cosmetic properties, a water-in-oil (w/o) cream
      containing small particles of solid paraffin was developed. Dynamic light
      scattering, freeze-fracture electron microscopy, polarization microscopy, and
      differential scanning calorimetry were used to characterize the cream. The
      preparation method essentially consisted of two steps. First, an aqueous
      dispersion of solid paraffin particles, with a mean diameter of 200 nm, was
      prepared with an oil-in-water (o/w) emulsifier. The aqueous dispersion proved to
      be extremely stable, and the particles had a spherical shape. Second, the aqueous
      dispersion was incorporated into the water phase of the cream during its
      production. After production of the cream, 68% of the paraffin was present as
      particles in the dispersed water phase. The size and shape of these particles did
      not change by the mechanical treatment during the production of the cream. At
      least 28% of the paraffin was present in the continuous oily phase, either as
      solid particles or in the form of a gel structure. At most, 4% of the paraffin
      was dissolved in this oily phase. The excess o/w emulsifier present in the
      aqueous phase of the w/o cream did not cause physical instability.

PMID- 7629739
TI  - Antispasmodic activity of xanthoxyline derivatives: structure-activity
      relationships.
AB  - The antispasmodic activity of several xanthoxyline derivatives against
      acetylcholine-induced contraction of the guinea pig ileum was evaluated in vitro.
      The acetophenones with two methoxyl groups, mainly in the 3,4 positions,
      exhibited potent antispasmodic activity. Modification of the hydroxyl group in
      xanthoxyline by the introduction of benzoyl, acetyl, or tosyl groups produced
      inactive compounds, whereas the introduction of benzyl or p-methoxybenzyl groups
      furnished compounds that were four- to eight-fold more potent than xanthoxyline.
      In marked contrast, the introduction of a methyl group gave a compound that
      caused contractant activity. Modification of the carbonyl group of xanthoxyline
      lead to inactive compounds, whereas the condensation of xanthoxyline with
      benzaldehydes gave chalkones that were about fivefold more potent than
      xanthoxyline. The introduction of benzyl and styrene groups, on the basis of the
      similarity with papaverine, improves the antispasmodic action of the xanthoxyline
      derivates. Our results suggest that the methoxyl and carbonyl groups are critical
      structural points for the antispasmodic activity of xanthoxyline derivatives. The
      hydroxyl group improves antispasmodic activity, but is not fundamental to its
      manifestation.

PMID- 7629740
TI  - Effect of dosing volume on gastrointestinal absorption in rats: analysis of the
      gastrointestinal disposition of L-glucose and estimation of in vivo intestinal
      membrane permeability.
AB  - The effect of the oral dosing volume (DV) on both gastric emptying and intestinal
      absorption was examined by analyzing the gastrointestinal disposition of a model
      solute, L-glucose, in rats. The amount of 14C-labeled L-glucose in the gastric
      and intestinal contents of sacrificed rats was measured at various times after
      administration, and the data were analyzed with a linear model, assuming first
      order gastric emptying followed by first-order intestinal absorption. The gastric
      emptying rate constant (kg) rose from 0.025 to 0.072 min-1 by increasing DV from
      0.1 to 3 mL/rat, whereas the intestinal absorption rate constant (ka) decreased
      from 0.031 to 0.015 min-1. This decrease in ka was attributed to an increase in
      the average intestinal lumen volume (Vav) from 24 to 39 microL/cm, assuming that
      the relationship ka = CLa,app/Vav holds (where CLa,app is the apparent intestinal
      membrane permeability clearance or the product of the apparent membrane
      permeability coefficient and surface area). The CLa,app (= kaVav), a measure of
      the in vivo intestinal membrane permeability, was 0.74 microL/cm/min for a DV
      value of 0.1 mL/rat and decreased only marginally by 20% for larger values of DV,
      suggesting an insignificant effect of DV on CLa,app. These results suggest that
      the accelerating effect of the increased kg, produced by the increased DV on the
      gastrointestinal absorption, may be canceled by the decrease in ka. A decrease in
      ka may lead to a decrease in the fraction absorbed. Finally, this study also
      provides a means for carrying out physiological modeling of drug absorption
      following oral administration.

PMID- 7629741
TI  - Effect of various enhancers on transdermal penetration of indomethacin and urea,
      and relationship between penetration parameters and enhancement factors.
AB  - The enhancing capacity of various chemicals, which are widely recognized as
      enhancers, for the transdermal penetration into full-thickness rat skin of a
      model lipophilic drug [indomethacin (IND)] and a hydrophilic permeant (urea) was
      estimated by an in vitro technique. In addition, the fluidity of the stratum
      corneum lipids, the partitioning of IND into skin, the lipid (ceramides)
      extraction from the stratum corneum by enhancers, and the IND solubility in
      enhancer vehicle were measured and related to the enhancing capacity. In vitro
      permeation experiments with hairless rat skin unequivocally revealed that the
      enhancers varied in abilities to enhance the fluxes of both agents. Laurocapram,
      isopropylmyristate (IPM), sodium oleate, and cineol increased fluxes of both
      agents to a great extent, but N-methyl-2-pyrrolidone (NMP), N,N-diethyl-m
      tolamide (DEET), and oleyl oleate were less effective acclerants. Many enhancers
      increased the fluidity of the lipids [with a threshold of approximately 0.6-0.8
      ns at 37 degrees C in the rotational correlation time (tau c)], the skin
      partitioning of IND, the extraction of ceramides from the cornified cells, and
      the thermodynamic activity of IND in vehicle (calculated from the solubility) to
      varying extents. A good correlation was observed between the increase in the
      fluidity of stratum corneum lipids and the partitioning of IND into skin, between
      the increase in the fluidity and the flux or the decrease in lag time for IND,
      between the removal of ceramides and the skin partitioning of IND, and between
      the removal of ceramides and the flux of urea (p < 0.05 in all cases).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7629742
TI  - Separation of basic drugs by packed-column supercritical fluid chromatography. 3.
      Stimulants.
AB  - A wide range of stimulants was rapidly and efficiently separated with symmetrical
      peak shapes with a tertiary supercritical mobile phase and a cyanopropyl liquid
      chromatography column. Compared with other drug families studied in this series,
      the stimulants exhibited a much broader range of retention. Several strong bases,
      including primary aliphatic amines, were easily eluted with a modified mobile
      phase. The stimulants were generally more retained than antipsychotic drugs.
      Compared with antidepressant drugs, a few stimulants behaved similarly, but most
      were more strongly retained. Modifier concentration proved to be the most
      effective means for changing both retention and selectivity. An over-the-counter
      eye drop solution (an aqueous buffer) was analyzed for tetrahydrozoline. The
      positive results with good peak shapes indicate that packed-column supercritical
      fluid chromatography is compatible with at least small aqueous samples.

PMID- 7629744
TI  - Particle size determination by automated microscopical imaging analysis with
      comparison to laser diffraction.
AB  - A rapid and precise microscopical analysis technique for the determination of
      particle size distribution has been developed. Particle size distribution was
      determined with a Carl Zeiss Axioplan microscope equipped with a computer
      controlled image analysis system. Area and volume measurements were performed on
      a number of particles and plotted against Feret's diameter to yield a
      distribution histogram. This technique was then applied to several compounds of
      pharmaceutical interest, and the resulting histograms were compared with
      histograms determined with a laser diffraction instrument. The reproducibility of
      the microscopical determination was good and the agreement between the two
      determinations was dependent on the crystalline shape.

PMID- 7629743
TI  - Stealth Me.PEG-PLA nanoparticles avoid uptake by the mononuclear phagocytes
      system.
AB  - Nanoparticles were prepared from methoxy poly(ethylene glycol)poly(d,l-lactic
      acid) block copolymers (Me.PEG-PLA) or blends of Me.PEG-PLA and PLA by the
      precipitation-solvent diffusion method. These nanoparticles, labeled by
      introducing [14C]PLA in the formulation, were shown to be more slowly captured by
      cultured THP-1 monocytes than F68-coated PLA nanoparticles, in a PEG chain-length
      dependent manner. In vivo, the half-life in plasma of the Me.PEG-PLA
      nanoparticles that were intravenously administered to rats is increased by a
      factor 180 compared with the F68-coated PLA nanoparticles. This mononuclear
      phagocytes system avoidance was explained according to a conformation model in
      which the PEG density at the surface of the particles is a key parameter.

PMID- 7629745
TI  - Synthesis and identification of the primary degradation product in a commercial
      ophthalmic formulation using NMR, MS, and a stability-indicating HPLC method for
      antazoline and naphazoline.
AB  - HPLC analysis of an anti-infective ophthalmic solution (Albalon-A), containing
      the active drugs naphazoline and antazoline, revealed a degradation peak of
      unknown identity. To elucidate the identity of the degradant, the active drugs
      were each hydrolyzed by refluxing at high pH, and their respective hydrolysis
      products were isolated and spectrally characterized by NMR, FT-IR, and MS for
      conclusive structure elucidation. The degradant's identity was confirmed by HPLC
      MS analysis of Albalon-A ophthalmic solution to be the antazoline hydrolysis
      product N-[(N-benzylanilino)acetyl]ethylenediamine (IV). A stability-indicating
      HPLC method was then developed which was able to resolve IV from the active
      drugs. This HPLC method was then validated for quantitating the active drugs and
      IV. Validation studies demonstrated linear UV response at 280 nm, recovery > 98%,
      good reproducibility, and a detection limit of 2 micrograms/mL IV. Overall, the
      data demonstrated that the HPLC method was quantitative and specific for
      antazoline, naphazoline, and IV. Analysis of an expired stabilitry lot of the
      ophthalmic solution indicated the concentration of IV was 0.002% (w/v).

PMID- 7629746
TI  - Surface pressure-area isotherms of mixed cyclosporin-poly(isobutylcyanoacrylate)
      monolayers spread at the air/water interface.
AB  - The pi-A isotherms of mixed monolayers of cyclosporin and
      poly(isobutylcyanoacrylate) (PIBCA) show that the molecular areas of cyclosporin
      and PIBCA are additive regardless of the pH of the substrate or the physical
      state of the monolayers. All these mixed films collapse at the same surface
      pressure; therefore, application of the two-dimensional phase rule implies that
      cyclosporin and PIBCA are immiscible at the interface. This conclusion may have
      important implications with regard to the formulation of PIBCA-cyclosporin
      nanoparticles for cyclosporin administration, though further research in this
      direction will require consideration of the role played by the coadjuvants used
      for PIBCA polymerization during nanoparticle formation.

PMID- 7629747
TI  - Absorption of bismuth from several bismuth compounds during in vivo perfusion of
      rat small intestine.
AB  - Evaluation of the amount of bismuth (Bi) absorbed from the gastrointestinal tract
      is important for assessment of the possible risks associated with the use of Bi
      compounds in the treatment of gastrointestinal disorders. We compared the
      absorption of Bi from media containing the equivalent of 1 g of elemental Bi from
      either Bi subnitrate (BSN), Bi subsalicylate (BSS), colloidal Bi subcitrate
      (CBS), Bi chloride (BiCl3), or Bi citrate (BCit) by an in vivo perfusion system
      of rat small intestine. The intestinal absorption was < 1% for all compounds, but
      higher from BCit and CBS than from BSN, BSS, and BiCl3. The dose dependency of Bi
      absorption from both CBS and BiCl3 in citrate buffer showed a nonlinear
      relationship between the concentration of Bi in perfusate and the concentration
      of Bi in blood after 60 min.

PMID- 7629748
TI  - Metabolism of omeprazole by gut flora in rats.

PMID- 7629749
TI  - The important role of albumin in determining the relative human blood stabilities
      of the camptothecin anticancer drugs.

PMID- 7629750
TI  - Effect of pH on injection phlebitis.
AB  - Formulation pH has been reported to be responsible for the incidence of
      phlebitis. In this study, the effect of pH on injection phlebitis is
      investigated. Buffers of varying pHs were examined for their ability to produce
      phlebitis in rabbits. Thermal measurements as well as visual evaluations were
      used for phlebitis quantitation. The results show that formulation pH between 3.0
      and 11.0 does not contribute to the incidence of phlebitis when administered as
      an iv bolus injection.

PMID- 7629751
TI  - In memoriam Manfred Bleuler (1903-1994).

PMID- 7629752
TI  - Cognitive screening of psychiatric patients.
AB  - The goal of the present study was to explore characteristic cognitive profiles
      which distinguish between psychiatric patients with and without organic mental
      disorder (OMD), using Neurobehavioral Cognitive Status Examination (NCSE), a
      brief screening battery. A mild degree of cognitive deficits was found to be
      common in the Non-OMD psychiatric group. The deficit was especially pronounced in
      the Memory domain. Patients in the OMD group demonstrated a higher frequency of
      moderate and severe impairment. The best discriminator was the scale assessing
      visuospatial constructional ability and visual memory. Verbal memory deficit in
      OMD patients was more severe than in Non-OMD patients. Implications for improving
      diagnostic sensitivity of cognitive screening are discussed.

PMID- 7629753
TI  - Analysis of the attention deficit in schizophrenia: a study of patients and their
      relatives in Ireland.
AB  - County Roscommon, a rural area in the western part of Ireland, was the site of a
      family study of schizophrenia. As part of this study, we have assessed several
      elements of attention, identified by principal components analysis in previous
      investigations, in a group of subjects with schizophrenia, first-degree relatives
      of subjects with schizophrenia and age- and education-matched controls. The
      schizophrenic subjects performed significantly more poorly than the controls; the
      performance of the relatives fell somewhere between the other two groups. Those
      relatives with a DSM-III-R diagnosis (most frequently, alcohol abuse or an
      affective disorder) tended to perform more poorly on some of the attention
      elements than relatives without a diagnosis; in contrast, control subjects with
      diagnoses were not distinguishable from other controls. The attention elements
      appeared to differ in their capacity to differentiate the groups and each seemed
      to have a distinctive profile. The effects of alcohol abuse were also considered.
      The results obtained with this cohort may provide clues concerning the
      pathophysiological basis of schizophrenia and the heterogeneity of its
      expression.

PMID- 7629754
TI  - Clinical and differential diagnostic aspects of treatment-resistant depression.
AB  - This study investigated treatment-resistant depressed patients. A sample of 49
      patients was selected from a review of 302 patients who had been consecutively
      evaluated at a tertiary care facility. Clinical records of these 49 patients
      revealed frequent misdiagnosis of depression subtype, relatively infrequent
      treatment with electroconvulsive therapy, and pharmacotherapy trials which often
      were too brief or characterized by inadequate dosing to be effective. A group of
      non-treatment resistant patients was matched for age, gender, and depressive
      subtype with 26 treatment-resistant patients. Treatment-resistant patients were
      less "atypical" and were more likely to have made a suicide attempt than the
      comparison patients. Although depression rating scales showed similar mean
      ratings for both groups, the TPQ revealed higher mean ratings for harm avoidance
      and lower mean ratings for novelty seeking for treatment-resistant patients. The
      implications of these findings are discussed.

PMID- 7629755
TI  - Treatment and diagnostic subtype in facial affect recognition in schizophrenia.
AB  - Patients with schizophrenia have been described as having deficits in the ability
      to recognize facial expressions of emotion. We report the results of a study on
      the effects of global psychopathology, positive and negative symptoms, diagnostic
      subtype, and antipsychotic medications, on the ability of subjects with
      schizophrenia to recognize facial affect. Eighteen SCID diagnosed patients with
      schizophrenia and ten matched controls were evaluated at a drug-free baseline for
      ability to identify facial expression expressed in a standardized series of
      photographs, with concurrent measures of global psychopathology, and positive and
      negative symptoms. At baseline patients were impaired in affect recognition
      relative to the normals, and impairment was not related to measures of
      psychopathology or positive or negative symptoms. Performance did not improve
      with antipsychotic treatment, and patients with paranoid schizophrenia had
      significantly better affect recognition abilities than non-paranoid patients.

PMID- 7629757
TI  - Clinical predictors of psychopathology in children and adolescents with Tourette
      Syndrome.
AB  - Tourette Syndrome (TS) is a neuropsychiatric disorder of childhood onset
      characterized by vocal and motor tics and associated psychopathologies. The
      current study was undertaken to explore the associations between tic
      symptomatology, related clinical variables and behavioral dysfunction within a
      cohort of TS subjects. Ninety-two child and adolescent TS subjects were rated
      through self-measure, and by parents on measures of tic symptomatology, OC
      characteristics, and dysfunctional behaviors including learning difficulties and
      attention deficits. Statistical modeling revealed associations among tic
      clusters, clinical items and behavioral measures, which were unique for the child
      and adolescent subgroups.

PMID- 7629756
TI  - Atrial natriuretic hormone inhibits corticotropin-releasing hormone-induced
      prolactin release in man.
AB  - Atrial natriuretic hormone (ANH) is found in heart myocytes, and also in the CNS.
      The inhibitory action of ANH on the hypothalamic-pituitary-adrenocortical (HPA)
      system has been established by in vivo and in vitro experiments, and could be of
      considerable importance: whereas several synergists to corticotropin-releasing
      hormone (CRH), the key hormone of the HPA system, are characterized in the past,
      until now ANH seems to be the only peptide which counterbalances the effects of
      CRH at the pituitary. As well as at the corticotroph, CRH has a stimulatory
      influence upon the lactotroph in vivo, and like ACTH and corticosteroids
      prolactin (PRL) is released in response to physical and cognitive challenges. To
      test the hypothesis of whether ANH also inhibits the CRH-mediated prolactin
      release a randomized, placebo-controlled, double-blind study in 12 males aged
      from 25 to 30 years was conducted. With regard to the diurnal variation of the
      HPA system activity we compared the prolactin release by 100 micrograms hCRH
      during a 30 min infusion of placebo, 150 micrograms ANH or 3 IU arginine
      vasopressin in the morning (08:00 h) and evening (19:00 h). Evaluation of morning
      and evening effects revealed that administration of hCRH led to a prompt rise of
      plasma PRL concentration. Infusion of ANH resulted in a significantly reduced
      maximum increment of PRL compared to placebo (0.83 +/- 0.87 vs 2.85 +/- 1.57
      ng/ml, mean +/- SD, n = 12, p < .001). In addition, the AUC values were
      significantly lower under ANH than in the placebo condition. Infusion of AVP did
      not significantly change the PRL response to CRH vs placebo.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7629759
TI  - The hyperthyroid economy.

PMID- 7629758
TI  - A calcium antagonist for the treatment of depressive episodes: single case
      reports.
AB  - Preclinical studies indicate that a disturbed intracellular calcium ion
      homeostasis is involved in the pathophysiology of affective disorders. Therefore
      some calcium antagonists were investigated, especially in the treatment of the
      manic syndrome. In the present study the calcium antagonist nimodipine was used
      in 10 out-patients with single or recurrent depressive episodes. As a result the
      mean HAMD scores changed from 26.5 to 9.9 after the individual nimodipine
      administration. These single case reports suggest an effective new therapy
      strategy for the treatment of affective dysregulations and give rise to
      controlled clinical studies with calcium antagonists.

PMID- 7629760
TI  - Georges Canguilhem: philosopher of disease.

PMID- 7629761
TI  - Localized amyloidosis of the genito-urinary tract.
AB  - Localized amyloidosis of the uro-genital tract is uncommon. It often simulates a
      neoplastic process. We describe our experience with three cases of localized
      amyloid of the bladder and one each of the ureter, prostate and corpora
      spongiosa.

PMID- 7629762
TI  - Diagnosis in chronic illness: disabling or enabling--the case of chronic fatigue
      syndrome.
AB  - This paper examines doctors' and patients' views on the consequences of an
      increasingly common symptomatic diagnosis, chronic fatigue syndrome (CFS). Two
      studies were conducted: the first comprised interviews with 20 general
      practitioners; the second was a longitudinal study, comprising three interviews
      over a period of 2 years with 50 people diagnosed with CFS. Contrasts were
      apparent between doctors' practical and ethical concerns about articulating a
      diagnosis of CFS and patients' experiences with and without such a diagnosis.
      Seventy per cent of the doctors were reluctant to articulate a diagnosis of CFS.
      They felt constrained by the scientific uncertainty regarding its aetiology and
      by a concern that diagnosis might become a disabling self-fulfilling prophecy.
      Patients, by contrast, highlighted the enabling aspects of a singular coherent
      diagnosis and emphasized the negative effects of having no explanation for their
      problems.

PMID- 7629764
TI  - Rectus sheath haematoma mimicking splenic enlargement.
AB  - Rectus sheath haematoma is uncommon and frequently misdiagnosed. In this paper an
      incorrect diagnosis of splenic enlargement was made. Ultrasound and computerized
      tomography revealed a large rectus sheath haematoma.

PMID- 7629763
TI  - Clinical audit of a specialist symptomatic breast clinic.
AB  - The efficient delivery of health care requires vigilant quality assurance. We
      describe the audit of our symptomatic breast clinic, which includes the option of
      a one-stop diagnostic service. A total of 134 new and 386 follow-up patients
      attended over four consecutive clinics. The majority of new referrals (68%) were
      seen by a consultant surgeon. Urgent referrals were seen significantly sooner
      than routine referrals (P < 0.001, chi 2-test), and the mean wait from designated
      appointment to seeing the surgeon was 37.6 (range-68 to 171) min. One-stop
      investigations were offered to 50 patients; of these, 36 women (72%) had a total
      wait of less than 2 h. For those not investigated at the same clinic, the mean
      time until investigations was 6.1 (range 0-36) days and mean recall was 2.7
      (range 1-8) weeks. Patients undergoing definitive surgery for cancer (n = 5) were
      operated on average 14.2 (range 7-27) days after the decision was made in
      outpatients, while the mean waiting time for non-cancer operations was 49.7
      (range 15-98) days. Objective audit on outpatient services is possible and can
      lead to improvement of services.

PMID- 7629765
TI  - Sarcoidosis presenting as Achilles tendinitis.
AB  - A case is described of sarcoidosis which presented with Achilles tendinitis. This
      association has not previously been reported.

PMID- 7629766
TI  - Hypersecretion of luteinizing hormone in the polycystic ovary syndrome and a
      novel hormone 'gonadotrophin surge attenuating factor'.

PMID- 7629767
TI  - Necrotizing fasciitis--the hazards of delay.
AB  - Necrotizing fasciitis was first described in a specific body region by Fournier
      in 1883 and as a more generalized condition by Meleney in 1924. The use of the
      term 'necrotizing fasciitis' can be attributed to Wilson in 1952. It is perceived
      as a rare condition, causing potentially devastating morbidity and frequent
      mortality. Prompt surgical management is generally accepted as the mainstay of
      treatment. This report illustrates the relationship between delay in definitive
      treatment and morbidity. Management options are also reviewed.

PMID- 7629768
TI  - Suicide in hospital: guidelines for prevention.
AB  - Few events in medical practice create such a sense of failure and guilt as the
      suicide of a hospital inpatient. The mortality rate is known to be increased in
      severe psychiatric illness just as it is in most other medical illnesses. The
      analogy, however, is not generally accepted. Death in cardiovascular or malignant
      disease, for example, is regarded in many cases as inevitable, a welcome relief
      from months of pain and suffering. Suicide, by contrast, is considered an
      unnatural event, one which is avoidable and preventable. In each case of suicide
      there is a belief among medical and nursing staff that they should have done
      better: they should have assessed the patient more carefully; been more aware of
      hints of suicide; provided closer supervision; or not agreed to the final period
      of leave.

PMID- 7629769
TI  - Another weapon too far: the anti-personnel laser.
AB  - The last decade has seen the development of military lasers designed to blind.
      Medical professionals dedicated to the prevention and treatment of visual
      disability, and particularly ophthalmologists under the terms of their newly
      acquired Royal Charter, have a responsibility to: document this new technology;
      explain its medical effects; and influence the threshold at which these weapons
      might be used. Proposals to prohibit anti-eye laser warfare at The United Nations
      Convention Conference in September 1995 present a unique opportunity to
      stigmatize blinding as a method of warfare.

PMID- 7629770
TI  - Combined coronary artery bypass surgery and abdominal aortic aneurysm repair.
AB  - The proper management of patients with asymptomatic abdominal aortic aneurysms
      and significant coexistent coronary artery disease is still debatable. The most
      common approach has been to perform the coronary artery bypass surgery some weeks
      before the abdominal aortic aneurysm repair in the hope of reducing the cardiac
      morbidity and mortality. We report our initial experience of three consecutive
      elective cases where the coronary artery bypass surgery and the abdominal aortic
      aneurysm repair were performed at one operation by the same operating surgeon.

PMID- 7629772
TI  - Acute bacterial prostatitis with osteomyelitis.
AB  - This short case presentation concerns the simultaneous occurrence of acute
      bacterial prostatitis and osteomyelitis due to staphylococcal bacteraemia
      hitherto unrecorded in the literature.

PMID- 7629771
TI  - Acrokeratosis paraneoplastica of Bazex in association with a metastatic
      neuroendocrine tumour.
AB  - Bazex syndrome is a rare cutaneous paraneoplastic phenomenon not previously
      reported in association with neuroendocrine tumours. We describe a patient who
      responded well to treatment with octreotide.

PMID- 7629773
TI  - Long-term sequelae of Palmar-Plantar erythrodysaesthesia syndrome secondary to 5
      fluorouracil therapy.
AB  - Palmar-Plantar erythrodyasesthesia syndrome has been reported as a temporary
      complication of 5-fluorouracil therapy consisting of a debilitating erythema and
      tenderness of the skin of hands and feet. The syndrome has previously been
      observed to respond rapidly to either temporary cessation of chemotherapy or
      pyridoxine with little residual disability. We report a case which was
      characterized by persistent morbidity necessitating prolonged discontinuation of
      treatment.

PMID- 7629774
TI  - Adult-onset congenital erythropoietic porphyria (Gunther's disease) presenting
      with thrombocytopenia.
AB  - Cutaneous signs of Gunther's disease (congenital erythropoietic porphyria)
      developing 5 years after the onset of symptomatic thrombocytopenia are described
      in a 65-year-old man. Persistent thrombocytopenia unresponsive to corticosteroids
      and immunoglobulin necessitated a splenectomy.

PMID- 7629775
TI  - Are ethical committees reliable?

PMID- 7629776
TI  - Dr Samuel Johnson's illness: idiopathic pulmonary fibrosis not bronchiectasis.

PMID- 7629777
TI  - The plague of Athens.

PMID- 7629778
TI  - Rickets and the crippled child: an historical perspective.

PMID- 7629779
TI  - Acts of commission, omission, and demission or pulling the plug.

PMID- 7629780
TI  - Non-attendance in outpatients.

PMID- 7629781
TI  - Parenteral copper and selenium supplementation of sheep on legume-grass pastures:
      biochemical and production responses in lambs to maternal treatment.
AB  - Liver and kidney copper (Cu) and selenium (Se) concentrations were studied over a
      7-month period after parenteral supplementation using Cu heptonate and barium
      (Ba) selenate in 44 8-month-old South African (SA) Mutton Merino wethers.
      Responses in plasma Cu and blood Se concentrations, as well as fecundity were
      also measured in a breeding flock of SA Mutton Merino ewes for 3 consecutive
      years. The effect of maternal supplementation with Cu and Se was assessed in
      terms of biochemical parameters and production responses in 654 lambs produced by
      these ewes. Parenteral treatments with Cu and Se raised liver and kidney
      concentrations (P < or = 0.05) for up to 7 months in wethers under conditions
      where liver Cu and Se respectively declined to concentrations below 30 mg/kg DM
      and 300 micrograms/kg dry matter (DM) in spring. Plasma Cu concentrations of
      breeding ewes which received Cu heptonate were increased (P < or = 0.05) by 18%
      relative to the control group in which concentrations declined to 91
      micrograms/dl during late pregnancy. Blood Se concentrations of control ewes
      exceeded 200 ng/ml, and were unaffected by parenteral Se supplementation.
      Survival of progeny of Cu heptonate treated ewes tended (P < or = 0.10) to be
      improved by 13% (0.68 vs 0.60). This tendency was accompanied by generally higher
      (P < or = 0.10) plasma Cu concentrations of these lambs relative to control lambs
      at 10 - 20 and 45 - 55 d of age. Lambs of Cu supplemented ewes that died prior to
      weaning, had higher (P < or = 0.05) liver Cu concentrations than control group
      contemporaries.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7629782
TI  - An investigation into the health status and diseases of wild dogs (Lycaon pictus)
      in the Kruger National Park.
AB  - Many factors have been cited as possible reasons for the decline in the number of
      wild dogs (Lycaon pictus), but few studies have provided supportive data. Between
      1990 and 1993, the dynamics of 10 wild dog packs in the southern district of the
      Kruger National Park in South Africa were monitored. Casual observations of the
      causes of disease and mortality in the entire population were also recorded.
      During the same period, 46 wild dogs were immobilised, weighed, and subjected to
      physical examination as well as the collection of blood and faecal specimens.
      External parasites were collected and blood smears were prepared. Serum specimens
      were subjected to routine blood chemistry analyses, hormone and serological
      assays and formalinised blood specimens and faeces were subjected to screening
      for endoparasites. The study population varied from 75 in 1990 to 123 in 1993
      with a survival rate of 29.9% for pups, 64.3% for yearlings and 69% for adults.
      Eighty per cent or more of the population were under 4 years of age. The cause of
      death in all wild dogs in the Kruger National Park could be established only in a
      small number of cases. Lions were responsible for the death of 20/62 wild dogs
      and disease caused the death of 6/62 wild dogs. All immobilised dogs were in a
      good physical condition, but 85% of dogs had one or more skin lesions. Potential
      life-threatening lesions (bitewounds inflicted by other dogs and lesions
      inflicted by a snare) occurred in 4 dogs. One male dog had only one testicle in
      the scortum. Twenty-six (93%) blood smears were positive for gametocytes of
      Hepatozoon sp., presumably H. canis, and in 2 dogs trophozoites of Babesia canis
      were seen. Eighty-six per cent of the specimens were positive for Dipetalonema
      reconditum. All dogs were infested with ticks and Haemaphysalis leachi, Amblyomma
      hebraeum, A. marmoreum, Boophilus decoloratus, Rhipicephalus simus, R. evertsi,
      R. appendiculatus and R. zambesiensis were identified. Ctenocephalides sp. and
      Echidnophaga larina were also identified. Taenia sp., Toxascaris canis and
      Ancylostoma caninum were present in faecal specimens. Antibody titres to
      adenovirus (26/31), B. canis (6/15), canine para-influenza virus (21/31),
      coronavirus (20/31), Coxiella burnetti (8/29), reovirus Type 3 (9/31), Rickettsia
      conori/africae (27/29), rotavirus (16/31) and Toxoplasma gondii (16/16) were
      found. The average serum urea concentration was higher (16.4 mmol/e) than that
      described for captive wild dogs, but other biochemical parameters were generally
      in agreement with values reported for captive wild dogs.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 7629783
TI  - Bovine brucellosis in the Highveld veterinary region: a preliminary report on the
      seroprevalence of brucellosis amongst adult beef cows in the region.
AB  - A preliminary survey to determine the seroprevalence of bovine brucellosis
      amongst adult beef cows in the Highveld veterinary region was conducted. Based on
      complement fixation tests, about 48.2% of seropositive beef herds and 4.47% of
      seropositive individual animals could be expected in the region. Since heifer
      calves on some farms apparently receive their doses of strain 19 vaccine later
      than the prescribed age of 4 to 8 months, more vaccination reactions than would
      normally occur, could be expected. The above figures should therefore be
      considered an over-estimation.

PMID- 7629784
TI  - Bovine tuberculosis survey in the Molopo district of the North West Province.
AB  - A survey was conducted in the Molopo district of the North West Province to
      determine the prevalence of bovine tuberculosis in the cattle population of
      57,000 grazing on communal and privately owned lands. Testing of cattle (n =
      9,675) for tuberculosis was done by means of the comparative intradermal
      tuberculin test. The prevalence was found to be 0.062%. The significance of this
      result, when compared to the reported incidence of tuberculosis within the human
      population of the district, is discussed.

PMID- 7629785
TI  - [A retrobulbar foreign body in a dog].
AB  - A 2-year-old dog was presented with a history of recurrent pain on opening its
      mouth. Clinical examination revealed conjunctivitis and chemosis of the left eye.
      Ultrasound examination of the eye revealed poor definition of the extra-ocular
      muscles. An orbitotomy was performed and a 50 mm-long silver of wood was removed
      from the retrobulbar tissues.

PMID- 7629786
TI  - [Acute blindness in a dog caused by sudden acquired retinal degeneration].
AB  - A 6-year-old male Boxer dog was presented with a history of acute blindness.
      Direct and consensual pupillary light reflexes were reduced. The fundus of both
      eyes appeared normal during ophthalmoscopic examination. Further diagnostic
      investigations included magnetic resonance imaging of the brain and
      electroretinography. Magnetic resonance imaging of the brain was normal, but the
      electroretinogram was extinguished. A diagnosis of sudden acquired retinal
      degeneration was made.

PMID- 7629787
TI  - Non-steroidal anti-inflammatory drugs in domestic animals: II Disposition and
      clinical indications.
AB  - Most non-steroidal anti-inflammatory drugs (NSAID's) have similar absorption and
      disposition characteristics. Absorption after oral administration is good,
      extensive plasma protein binding results in a small volume of distribution, and
      excretion of metabolites occurs mainly in the urine after hepatic
      biotransformation of the active drug. The main clinical indications for use of
      NSAID's are anti-inflammatory, analgesic and antipyretic, and an increasing list
      of new indications are continually being found. The disposition, pharmacokinetics
      and clinical indications of non-steroidal anti-inflammatory drugs in domestic
      animals are reviewed.

PMID- 7629788
TI  - Pharmacokinetics of ammonium tetrathiomolybdate following intravenous
      administration in sheep.
AB  - South African Mutton Merino wethers (n = 5) were each dosed with 2.5 g copper
      oxide needles. Three weeks later the sheep were placed on stainless steel
      metabolic crates to facilitate urine and faecal collection. Ammonium
      tetrathiomolybdate (TTM) (1.7 mg kg-1) was administered intravenously, blood
      samples were collected at intervals and different pharmacokinetic parameters for
      TTM were determined and are presented. Serum molybdenum concentration data were
      best described by a 2-compartmental open model with first order rate constants.
      An elimination half-life (T1/2 beta) of 396.8 min, steady state volume of
      distribution (Vdss) of 0.8 e kg-1 and total body clearance (C1B) of 1.53 ml kg-1
      min-1 were observed using non-linear compartmental analysis. A significant (p <
      or = 0.05) increase in molybdenum excretion in the faeces occurred at 24 and 48 h
      following TTM administration. No increase in faecal and urinary copper excretion
      could be demonstrated, probably because the sheep were not copper-loaded.
      However, before a shorter dosage interval can be recommended for the treatment of
      sheep during the haemolytic crisis of chronic copper poisoning, further research
      in copper-loaded sheep is indicated.

PMID- 7629789
TI  - Synthesis, resolution, and biological evaluation of the four stereoisomers of 4
      methylglutamic acid: selective probes of kainate receptors.

PMID- 7629790
TI  - New orally active serine protease inhibitors.

PMID- 7629791
TI  - 5-Methyl-1-(3-pyridylcarbamoyl)-1,2,3,5-tetrahydropyrrolo[2,3-f]indole: a novel 5
      HT2C/5-HT2B receptor antagonist with improved affinity, selectivity, and oral
      activity.
AB  - The preparation of a series of conformationally restricted analogues of
      indolylurea 1, namely tetrahydropyrroloindoles and tetrahydropyrroloquinolines,
      is described. The binding affinities of these compounds at 5-HT2A, 5-HT2B, and 5
      HT2C receptors were determined. Of these compounds, the 1,2,3,5
      tetrahydropyrrolo[2,3-f]indole derivative, compound 11, was found to have high
      affinity for the 5-HT2C (pKI 8.0) and 5-HT2B receptors (pA2 8.5), with excellent
      selectivity over the 5-HT2A and various other receptors (pKI < 6). 11 is also
      considerably more active than 1 in both an in vitro functional model, 5-HT
      stimulated phosphoinositol hydrolysis (pKB 8.8), and an in vivo functional model,
      mCPP-induced hypolocomotion (ID50 5.5 mg/kg po). 11 should therefore be of
      significant utility as a pharmacological tool to delineate the functional
      significance of blockade of 5-HT2B and 5-HT2C receptors.

PMID- 7629793
TI  - Cyclic variations of 3-quinolinecarboxamides and effects on antiherpetic
      activity.
AB  - Supported by the antiherpetic properties of 3-quinolinecarboxamides and the
      importance of the planar intramolecular H-bonded beta-keto amide pharmacophore, a
      series of novel conformationally rigid analogues that contain a heterocyclic
      bridge between the 3- and 4-positions of the quinoline ring have been evaluated.
      Two isoxazolo-fused derivatives 17 and 23 displayed good in vitro antiherpetic
      potency that was similar to that of 1, the 3-quinolinecarboxamide that served as
      the comparison structure for this study. The pyrazolo, pyrrolo, and pyrimido
      derivatives showed considerably less or no activity. In vitro activity did not
      translate to in vivo efficacy. For 17, the lack of in vivo activity is likely a
      consequence of insufficient plasma drug levels (both Cmax and duration) in mice
      relative to the MIC versus HSV-2.

PMID- 7629792
TI  - Synthesis and antibacterial activity of some novel 1-substituted 1,4-dihydro-4
      oxo-7-pyridinyl-3-quinolinecarboxylic acids. Potent antistaphylococcal agents.
AB  - The palladium-catalyzed coupling of 3- and 4-(trialkylstannyl)pyridines with 7
      bromo or 7-chloro 1-substituted 1,4-dihydro-4-oxo-3-quinolinecarboxylates has
      provided access to the corresponding 1-substituted 1,4-dihydro-4-oxo-7-pyridinyl
      3-quinolinecarboxylic acids. The antibacterial activity of these derivatives was
      studied with the finding that the optimal 1- and 7-position substituents for Gram
      positive activity are cyclopropyl and 4-(2,6-dimethylpyridinyl), respectively. We
      find that for the fluorine-substituted derivatives studied, the position of the
      fluorine on the quinolone nucleus or the number of fluorine atoms does not seem
      to be important for good Gram positive activity. For 1-cyclopropyl 7-(2,6
      dimethyl-4-pyridinyl) derivatives, the 6-fluoro 4a, 8-fluoro 10d, 6,8-difluoro
      10b, and 5,6,8-trifluoro 8, all provided equal antibacterial activity against
      Staphylococcus aureus ATCC 29213. There is also a correlation between the
      substitution on the 7-(4-pyridinyl) group and the Gram positive activity,
      particularly for S. aureus, clearly indicating that the 2,6-dimethylpyridinyl
      group is optimal. The MIC50 value for the most potent agents in this study
      against S. aureus ATCC 29213 is 0.008 microgram/mL. By comparison, ciprofloxacin
      and aminopyrrolidine 28 gave values of 0.25 and 0.015 microgram/mL, respectively,
      against this organism.

PMID- 7629794
TI  - Novel and potent adenosine 3',5'-cyclic phosphate phosphodiesterase III
      inhibitors: thiazolo[4,5-b][1,6]naphthyridin-2-ones.
AB  - The transformation of 3-bromo-1,6-naphthyridin-2(1H)-ones 8 to thiazolo[4,5
      b][1,6]naphthyridin-2(1H)-ones 12 resulted in a 2-9-fold increase in cAMP
      phosphodiesterase (PDE) III inhibitory potency. Unlike the secondary binding
      sites on the cAMP PDE III isozyme which interact with the methyl group of
      milrinone (2) and CI-930 (4), the site which interacts with the 5-substituents of
      1,6-naphthyridin-2(1H)-ones and the 8-substituents of thiazolo[4,5
      b][1,6]naphthyridin-2(1H)-ones 12 is able to accommodate a diverse group of
      substituents which have different steric and electronic requirements.

PMID- 7629795
TI  - 4,5-Dihydro-3-(methanesulfonamidophenyl)-1-phenyl-1H-2,4-benzodiazepines: a novel
      class III antiarrhythmic agents.
AB  - A series of 4,5-dihydro-3-[2-(methanesulfonamidophenyl)ethyl]-1-phenyl- 1H-2,4
      benzodiazepines has been identified as potential antiarrhythmic agents that
      interact at the delayed rectifier myocardial potassium channels (IKr) and prolong
      the ventricular effective refractory period (ERP) in rabbit isolated Langendorff
      heart preparations. Structure-activity relationship (SAR) studies based upon
      prolongation of ERP indicate that placement of the sulfonamido group is important
      for potent activity in this model. Furthermore, methanesulfonamido has enhanced
      activity over its ethyl or trifluoromethyl analogs. Slightly greater activity was
      observed in compounds that had a heteroatom in the ethyl bridge that connects the
      methanesulfonamidophenyl to the benzodiazepine. Further incremental improvements
      in activity were noted when the 1-phenyl ring was substituted with a variety of
      substituents. Chirality of the compounds of interest in this series does not
      appear to influence activity in this model. Several of these compounds were
      chosen for advanced evaluation, and all possess high selectivity for blockade of
      potassium current in hearts relative to other ion channels. In addition, these
      compounds prolong cardiac refractoriness in dogs following oral dosing. Thus,
      these agents may represent potential new class III agents, but with the potential
      liability of myocardial IKr blockers.

PMID- 7629796
TI  - Novel inhibitors of the nuclear factor of activated T cells (NFAT)-mediated
      transcription of beta-galactosidase: potential immunosuppressive and
      antiinflammatory agents.
AB  - The preparation of a series of quinazoline-2,4-diones, 1-3, and pyrrolo[3,4
      d]pyrimidine-2,4-diones, 4-8 is described. A small number of quinazolinedione
      analogs were identified from random screening to possess low micromolar (1.3-4.4
      microM) potency in the nuclear factor of activated T cells-1-regulated beta
      galactosidase expression assay. An expanded analog search resulted in identifying
      pyrrolopyrimidinedione 4b which is 5-10-fold (0.26 microM) more potent than the
      quinazolinediones. Replacement of the benzyl group with naphthyl led to greater
      potency and conformationally restricted analogs 4u-w. The naphthyl and
      acenaphthyl analogs are 10-100 times more potent inhibitors of beta-galactosidase
      expression than 4b. Binding affinity data for displacement of radiolabeled 4s
      from Jurkat cell membranes reflected an excellent correlation with the IC50 value
      for inhibition of beta-galactosidase activity. These products, whose structure
      activity relationships are discussed, are of interest as potential agents for
      preventing interleukin-2 gene transcription.

PMID- 7629797
TI  - Inhibition of matrix metalloproteinases by hydroxamates containing heteroatom
      based modifications of the P1' group.
AB  - In this study, structure-based drug design of matrix metalloproteinase inhibitors
      [human fibroblast collagenase (HFC), human fibroblast stromelysin (HFS), and
      human neutrophil collagenase (HNC)] was utilized in the development of potent
      hydroxamates which contain novel, heteroatom-based modifications of the P1'
      group. A series containing a P1' butyramide group resulted in a nanomolar potent
      and selective HNC inhibitor as well as a dual HFS/HNC inhibitor. Benzylic ethers
      with a four- or five-carbon methylene linker in the P1' position also produced
      nanomolar potent HFS/HNC inhibition and micromolar potent HFC inhibition as
      expected. Surprisingly, the phenolic ethers of the same overall length as the
      benzylic ethers showed nanomolar potencies against HFC, as well as HFS and HNC.
      The potency profile of the phenolic ethers was optimized by structure-activity
      relationships of the phenolic group and the C-terminal amide. These inhibitors
      may help elucidate the in vivo roles of matrix metalloproteinases in normal and
      disease states.

PMID- 7629798
TI  - Synthesis and structure-activity relationships of 6-heterocyclic-substituted
      purines as inactivation modifiers of cardiac sodium channels.
AB  - Purine-based analogs of SDZ 211-500 (5) were prepared and evaluated as
      inactivation modifiers of guinea pig or human cardiac sodium (Na) channels
      expressed in Xenopus oocytes. Substances which remove or slow the Na channel
      inactivation process in cardiac tissue are anticipated to prolong the effective
      refractory period and increase inotropy and thus have potential utility as
      antiarrhythmic agents. Heterocyclic substitution at the 6-position of the purine
      ring resulted in compounds with increased Na activity and potency, with 5
      membered heterocycles being optimal. Only minor modifications to the
      benzhydrylpiperazine side chain were tolerated. Selected compounds which delayed
      the inactivation of Na channels were found to increase refractoriness and
      contractility in a rabbit Langendorff heart model, consistent with the cellular
      mechanism. Activity in both the oocyte and rabbit heart assays was specific to
      the S enantiomers. Preliminary in vivo activity has been demonstrated following
      intravenous infusion. The most promising compound on the basis of in vitro data
      is the formylpyrrole (S)-74, which is 25-fold more potent than DPI 201-106 (1) in
      the human heart Na channel assay.

PMID- 7629799
TI  - 1,1-Bisphosphonate squalene synthase inhibitors: interplay between the isoprenoid
      subunit and the diphosphate surrogate.
AB  - Inhibitors of squalene synthase have the potential to be superior cholesterol
      lowering agents. We previously disclosed that lipophilic 1,1-bisphosphonates I
      are potent squalene synthase inhibitors and orally active cholesterol-lowering
      agents in animal models (Ciosek, C. P., Jr.; et al. J. Biol. Chem. 1993, 268,
      24832-24837). In this paper, we describe modifications to the bisphosphonate
      moiety, in an attempt to reduce the number of acidic functions contained in these
      inhibitors. Replacing one of the acidic groups with a methyl (II, R2 = CH3)
      results in potent inhibitors when paired with a close mimic of the naturally
      occurring farnesyl moiety (R1 = farnesylethyl) but not when paired with the
      shorter isoprene surrogates (R1 = geranylethyl or 4-biphenylpropyl). In contrast,
      all three corresponding bisphosphonates I are potent squalene synthase
      inhibitors. Inhibitory potency is recovered with the shorter isoprene surrogates
      when R2 is CH2OH or CH2OCH3. It is proposed that these R2 groups serve as
      hydrogen bond acceptors with the active site of the enzyme. The properties of
      these compounds as cholesterol biosynthesis inhibitors in rats are described, and
      synthetic routes to these and related compounds are detailed.

PMID- 7629800
TI  - Specific sequestering agents for the actinides. 28. Synthesis and initial
      evaluation of multidentate 4-carbamoyl-3-hydroxyl-1-methyl-2(1H)-pyridinone
      ligands for in vivo plutonium(IV) chelation.
AB  - A new family of chelating agents based on 4-(substituted-carbamoyl)-3-hydroxy-2
      pyridinones is reported. These have optional terminal substituents on the
      nitrogens, and the hydroxypyridonate (HOPO) rings are attached to molecular
      backbones through amide linkages. A very important feature of the methyl
      substituted ligand derivatives (Me-3,2-HOPOs) is that, similarly to the
      catechoylamide complexes of the siderophore enterobactin and its analogs, these
      HOPO derivatives form strong hydrogen bonds between the amide proton and the
      adjacent oxygen of the phenolate in the metal complex; this enhances the
      stability of the complex. This rigidity helps to explain the great affinity of
      the Me-3,2-HOPO ligands for plutonium(IV), as observed here under physiological
      conditions. All 13 compounds studied significantly enhanced Pu excretion from
      mice compared with Pu-injected controls. Eight of the ligands studied promoted
      significantly more Pu excretion than an equal molar amount of CaNa3-DTPA (the
      compound in present clinical use). Five injected and two orally administered Me
      3,2-HOPO ligands promoted as much or slightly more Pu excretion than an equal
      molar amount of the octadentate 3,4,3-LI(1,2-HOPO), the previously most effective
      in vivo ligand. Surprisingly, although plutonium has an eight-coordination
      requirement, tetra- and hexadentate Me-3,2-HOPO ligands were essentially as
      effective as the one octadentate ligand studied. These observations suggest that
      even the tetradentate Me-3,2-HOPO ligands compete with mammalian transferrin for
      Pu(IV). For the three most promising compounds, there is no acute toxicity seen
      up to the highest dose administered, which was 1000 mumol/kg. One compound, the
      hexadentate TREN-(Me-3,2-HOPO), is particularly effective, either injected or
      orally, and an exceptionally good in vivo chelator of several actinides in
      addition to Pu(IV). Three of these compounds studied have low toxicity and are
      relatively simple and inexpensive to prepare. They are promising therapeutic
      agents.

PMID- 7629801
TI  - 2,4-Diaminopyrido[3,2-d]pyrimidine inhibitors of dihydrofolate reductase from
      Pneumocystis carinii and Toxoplasma gondii.
AB  - Six previously unknown 2,4-diamino-6-(anilinomethyl)- and 2,4-diamino-6-[(N
      methylanilino)-methyl]pyrido[3,2-d]pyrimidines (5-10) were synthesized from 2,4
      diamino-6-(bromomethyl)-pyrido[3,2-d]pyrimidine hydrobromide (11.HBr) by
      treatment with the appropriate aniline or N-methylaniline in dimethylformamide at
      room temperature, with or without NaHCO3 present. Compounds 5-10 were tested as
      inhibitors of dihydrofolate reductase from Pneumocystis carinii, Toxoplasma
      gondii, and rat liver as a part of a larger effort directed toward the discovery
      of lipophilic nonclassical antifolates combining high enzyme selectivity and high
      potency. Of the six analogues tested, the most potent and selective against T.
      gondii DHFR was 2,4-diamino-6-[(3',4',5'-trimethoxy-N
      methylanilono)methyl]pyrido[ 3,2-d d pyrimidine (7), which had an IC50 of 0.0047
      microM against this enzyme as compared with 0.026 microM against the rat liver
      enzyme. The potency of 7 against T. gondii DHFR was similar to that of
      trimetrexate (TMQ, 1) and piritrexim (PTX, 2) but was > 500-fold greater than
      that of trimethoprim (TMP, 3). However, while 7 was more selective than either
      TMQ (19x) or PTX (63x) against this enzyme, its selectivity in comparison with
      TMP was 8-fold lower. 2,4-Diamino-6-[3',4',5'-trimethoxyanilino)methyl]pyrido[3,2
      d]pyri midin e (6) was 17-fold less active than 7 and was also less selective.
      2,4-Diamino-6-[(3',4'-dichloro-N-methylanilino)methyl]pyrido[3, 2-d]pyrimidine
      (10) had an IC50 of 0.022 microM against P. carinii DHFR and was comparable in
      potency to TMQ and PTX. The species selectivity of 10 for P. carinii versus rat
      liver DHFR was greater than that of either TMQ (21-fold) or PTX (31-fold). On the
      other hand, even though 10 was slightly more active than TMQ against the P.
      carinii enzyme, its selectivity was 7-fold lower than that of TMP. Thus, the goal
      of combining high enzyme binding activity, which is characteristic of the fused
      ring compounds TMQ and PTX, with high selectivity for T. gondii and P. carinii
      DHFR versus rat liver DHFR, which is characteristic of the monocyclic compound
      TMP, remained unmet in this limited series.

PMID- 7629803
TI  - Novel 1,2-dithiins: synthesis, molecular modeling studies, and antifungal
      activity.
AB  - The first structure-activity study involving the 1,2-dithiin class of compounds
      (1,2-dithiacyclohexadienes) is herein reported. A series of 3,6-disubstituted 1,2
      dithiins was synthesized from dithiins 1d and 1e and evaluated as antifungal
      agents. A new and versatile synthesis of dithiins 1d and 1e is reported which is
      amenable to scale-up at the kilogram level. The novelty of the process derives
      from the use of beta-mercaptopropionitrile as the thiophile, relying on a beta
      elimination strategy and subsequent oxidation to create the 1,2-dithiin ring.
      Optimal geometries of dithiins 1d, 18i, and 45 and model dithiin 61 were
      determined by molecular mechanics and Hartree-Fock molecular orbital
      calculations. Two possible mechanisms of action are presented for the 1,2-dithiin
      class of compounds to explain their observed antifungal activities against
      Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus.

PMID- 7629802
TI  - Structure-activity relationships for inhibition of type 1 and 2 human 5 alpha
      reductase and human adrenal 3 beta-hydroxy-delta 5-steroid dehydrogenase/3-keto
      delta 5-steroid isomerase by 6-azaandrost-4-en-3-ones: optimization of the C17
      substituent.
AB  - A variety of C17 amide-substituted 6-azaandrost-4-en-3-ones were prepared and
      tested versus human type 1 and 2 steroid 5 alpha-reductase (5AR) and human
      adrenal 3 beta-hydroxy-delta 5-steroid dehydrogenase/3-keto-delta 5-steroid
      isomerase (3BHSD) in order to optimize potency versus both isozymes of 5AR and
      selectivity versus 3BHSD. Two series of potent and selective C17 amides were
      discovered, 2,5-disubstituted anilides and (arylcycloalkyl)amides. Compounds from
      each series with picomolar IC50's versus human type 2 5AR and low nanomolar to
      picomolar IC50's versus human type 1 5AR possessing 100-500-fold selectivity
      versus 3BHSD were identified. A conformational model to predict 3BHSD potency was
      developed which could rationalize 3BHSD potency within three different series of
      compounds. Evaluation of some optimal compounds from this series in a chronic
      castrated rat model of 5AR inhibitor induced prostate involution, and
      pharmacokinetic measurements identified compounds (9, 12, 16, and 29) with good
      in vivo efficacy and half-life in the dog. An intact rat model of in vivo
      selectivity for 5AR versus 3BHSD inhibition was also developed. Dual inhibitors
      of both human 5AR's may show advantages over type 2 selective 5AR inhibitors,
      such as finasteride (1), in the treatment of disease states which depend upon
      dihydrotestosterone.

PMID- 7629805
TI  - Synthesis of carbon-11-, fluorine-18-, and iodine-125-labeled GABAA-gated
      chloride ion channel blockers: substituted 5-tert-butyl-2-phenyl-1,3-dithianes
      and -dithiane oxides.
AB  - A series of substituted 5-tert-butyl-2-phenyl-1,3-dithianes and 5-tert-butyl-2
      phenyl-1,1,3,3-tetraoxo-1,3-dithianes was synthesized as ligands for the GABAA
      receptor complex-associated neuronal chloride ion channels. The in vitro binding
      affinities of these compounds for the GABA-gated chloride ion channel were
      determined by their ability to compete with [3H]TBOB for binding to rat brain
      slices. Of the eight compounds tested, trans-5-tert-butyl-2-(4-cyanophenyl)-2
      methyl-1,1,3,3-tetraoxo+ ++-1,3-dithiane, 9b, trans-5-tert-butyl-2-(4
      fluorophenyl)-1,1,3,3-tetraoxo-1,3-dithian e, 10, and trans-5-tert-butyl-2-(4
      iodophenyl)-2-methyl-1,1,3,3-tetraoxo-1,3- dithiane, 11, showed moderately high
      binding affinities (Ki = 41, 180, and 105 nM, respectively). Four radioligand
      candidates from this series, 5-tert-butyl-2-(4-cyanophenyl)-2-[11C]methyl-1,3
      dithiane, [11C]6, 5-tert-butyl-2-(4-[18F]fluorophenyl)-1,3-dithiane, [18F]7, 5
      tert-butyl-2-(4-[18F]-fluorophenyl)-1,1,3,3-tetraoxo-1,3- dithiane, [18F]10, and
      5-tert-butyl-2-(4-[125I]iodophenyl)-2-methyl-1,1,3,3- tetraoxo-1,3-dithiane,
      [125I]11, have been successfully prepared for evaluation as in vivo imaging
      agents useful for positron emission tomography and single photon emission
      computed tomography. Preliminary in vivo studies indicate significant uptake into
      mouse brain for [18F]7, [18F]10, and [125I]11.

PMID- 7629804
TI  - Gonadotropin-releasing hormone antagonists: novel members of the azaline B
      family.
AB  - A series of antagonists of gonadotropin-releasing hormone (GnRH) homologous to
      azaline B ([Ac-DNal1,DCpa2,DPal3,Aph5(Atz),DAph6+ ++(Atz),ILys8,DAla10]GnRH) was
      synthesized, characterized, and tested in a rat antiovulatory assay (AOA).
      Selected analogues were also tested in both an in vitro dispersed rat pituitary
      cell culture assay for inhibition of GnRH-stimulated luteinizing hormone release
      and an in vitro histamine release assay. The duration of action of some of the
      most potent and safest analogues in those assays was also determined in the
      castrated male rat in order to measure the extent (efficacy and duration of
      action) of inhibition of luteinizing hormone release. Structurally, this series
      of analogues has novel substitutions (X and Y) in the structure of the azaline B
      precursor: [Ac-DNal1,DCpa2,DPal3,-Aph5(X),DAph6(Y),++ +ILys8,DAla10]GnRH. These
      substitutions were designed to confer increased hydrophilicity as compared to
      that of azaline B (determined by relative retention times on a C18 reverse phase
      column using a triethylammonium phosphate buffer at pH 7.3) or to make them more
      easily accessible synthetically. Some bulky substituents were introduced in order
      to probe the spatial limitations of the receptor's cavity. These substitutions
      include acylated 4-aminophenylalanine at positions 5 and/or 6 (29 analogues), N
      alpha-methylated backbone substitutions (six analogues), N omega
      isopropylaminophenylalanine at position 8, and hydrophilic amino acids at
      position 1. Out of 20 novel analogues tested for long duration of action in this
      series, only seven ([Ac-DNal1,DCpa2,DPal3,Aph5,DAph6,ILys8 ,DAla10]GnRH, [Ac
      DNal1,DCpa2,DPal3,Aph5(For),DAph6(For) ,ILys8,DAla10]GnRH, [Ac
      DNal1,DCpa2,DPal3,Aph5(Ac),DAph6(Ac),- ILys8,DAla10]GnRH (acyline), [Ac
      DNal1,DCpa2,DPal3,Aph5(Pio),DAph6++ +(Pio),ILys8,DAla10]GnRH, [Ac
      DNal1,DCpa2,DPal3,Aph5(Atz),DAph6++ +(Ac),ILys8,DAla10]GnRH, [Ac
      DNalDCpa2,DPal3,Aph5(Atz-beta Ala),DAph6(Atz-beta Ala),ILys8, DAla10]GnRH, [Ac
      DNal1,DCpa2,DPal3,Aph5(Atz-Gab), DAph6(Atz-Gab),ILys8,DAla10]GnRH) had relative
      potencies and/or duration of action comparable to those of azaline B. The others
      were one-half to one-tenth as effective as azaline B. N alpha-Methylated backbone
      substitutions at position 5 yielded analogues that were significantly more
      hydrophilic presumably because of the breakage of the NH alpha-Tyr5 to Arg8-CO
      hydrogen bond reported to stabilize a beta-turn encompassing residues 5-8 and
      which favored beta-sheet formation as shown earlier by Haviv et al. This
      substitution resulted, however, in an increased potency in the histamine release
      assay and in significantly shorter duration of action. Similarly, attempts at
      replacing isopropyllysine in position 8 by either isopropyl-4-aminophenylalanine
      or isopropyl-4-(aminomethyl)phenylalanine resulted in loss of potency in the AOA.
      Changes in chirality at position 1 or 10 resulted in analogues that were one
      tenth and one-half as potent, respectively, as acyline.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 7629806
TI  - Synthesis and biological evaluation of 5-fluoro-2'-deoxyuridine phosphoramidate
      analogs.
AB  - A series of alkylating phosphoramidate analogs of 5-fluoro-2'-deoxyuridine has
      been prepared and their growth inhibitory activity evaluated against murine L1210
      leukemia and B16 melanoma cells in vitro. These compounds were designed to
      undergo intracellular release of the phosphoramidate anions, which it was hoped
      would function as irreversible inhibitors of thymidylate synthase. The
      expectation was that binding of the nucleoside moiety would be followed by
      alkylation of the enzyme via the phosphoramidate. The chloride, bromide, iodide,
      and tosylate analogs were highly potent inhibitors of L1210 cell proliferation,
      with increased inhibition observed at both higher drug concentrations and longer
      exposure times. Addition of thymidine completely reversed the inhibition for all
      compounds, suggesting that these compounds are acting via inhibition of
      thymidylate synthase. Although the nonalkylating morpholine analog 1f was ca. 50
      fold less potent than the methyl(chloroethyl)amino compound, the piperidine
      analog 1g was only 2-fold less potent, confirming that nitrogen basicity may be
      as important as the presence of an alkylating group. Addition of thymidine
      reversed the growth inhibition of the morpholine and piperidine analogs,
      suggesting that these compounds may also undergo intracellular conversion to 5
      fluoro-2'-deoxyuridine 5'monophosphate. The thymidine and deoxyuridine
      derivatives 2 and 3 showed minimal growth inhibition in the L1210 assay. The
      alkylating analogs showed modest cytotoxicity against B16 melanoma cells, and the
      potency of the analogs was more dependent upon the alkylating moiety than on the
      5-substituent.

PMID- 7629807
TI  - Prediction of drug binding affinities by comparative binding energy analysis.
AB  - A new computational method for deducing quantitative structure-activity
      relationships (QSARs) using structural data from ligand-macromolecule complexes
      is presented. First, the ligand-macromolecule interaction energy is computed for
      a set of ligands using molecular mechanics calculations. Then, by selecting and
      scaling components of the ligand-macromolecule interaction energy that show good
      predictive ability, a regression equation is obtained in which activity is
      correlated with the interaction energies of parts of the ligands and key regions
      of the macromolecule. Application to the interaction of the human synovial fluid
      phospholipase A2 with 26 inhibitors indicates that the derived QSAR has good
      predictive ability and provides insight into the mechanism of enzyme inhibition.
      The method, which we term comparative binding energy (COMBINE) analysis, is
      expected to be applicable to ligand-receptor interactions in a range of contexts
      including rational drug design, host-guest systems, and protein engineering.

PMID- 7629808
TI  - Novel, potent, and selective 5-HT3 receptor antagonists based on the
      arylpiperazine skeleton: synthesis, structure, biological activity, and
      comparative molecular field analysis studies.
AB  - Synthesis and pharmacological evaluation of a series of condensed quinoline
      derivatives bearing a basic nitrogen on piperazine or [(dimethylamino)ethyl]thio
      moieties attached at the 2-position of the quinoline nucleus are described. 5-HT
      receptor binding studies revealed, for most of the compounds studied, nanomolar
      affinity for the 5-HT3 receptor subtype. The most active compound,
      benzopyrano[3,4-c]quinoline derivative 5f, displayed a Ki value very similar to
      that reported for quipazine along with an improved selectivity. Functional and in
      vivo testing carried out on three selected compounds showed that 5f,j,n are
      potent 5-HT3 receptor antagonists with potencies in the same range as the best
      known 5-HT3 receptor antagonists ondansetron, tropisetron, and zacopride. The
      crystal and molecular structures of compounds 5f,j,n were determined by single
      crystal X-ray diffraction and used as starting structures for molecular modeling
      studies. Comparative molecular field analysis (CoMFA) was applied to binding
      constants of compounds 5a-p and 6a-h. The cross-validated r2, derived from
      partial least-squares calculations, indicated a good predictive capacity for
      affinity values in the series of compounds investigated. Evidence for the
      prediction capacity is provided in the form of plots of actual vs predicted pKi
      values. The steric and electrostatic features of the CoMFA-derived model are
      presented as standard coefficient contour maps of steric and electrostatic
      fields.

PMID- 7629810
TI  - Synthesis and biochemical evaluation of adenosylspermidine, a nucleoside
      polyamine adduct inhibitor of spermidine synthase.
AB  - The synthesis of a new class of multisubstrate adduct inhibitors of polyamine
      biosynthesis has been investigated. The first target compound, designed to
      inhibit spermidine synthase, was obtained and proved to be a very potent
      inhibitor of that enzyme. Two synthetic routes to effect the coupling of the
      polyamine spermidine to the nucleoside adenosine were studied. The first route
      involved a proposed Wittig or Julia olefination reaction to form the critical 5'
      6' carbon-carbon bond between the nucleoside and polyamine moieties. This route
      failed due to a facile beta-elimination of a portion of the side chain from a
      carbanion intermediate during either coupling reaction. A second route involved a
      reductive amination approach and proved to be successful. The new inhibitor,
      given the trivial name adenosylspermidine, is the most potent inhibitor of
      spermidine synthase prepared to date.

PMID- 7629809
TI  - Amino acid side chain descriptors for quantitative structure-activity
      relationship studies of peptide analogues.
AB  - This report describes a new set of amino acid side chain descriptors, the
      isotropic surface area (ISA), and the electronic charge index (ECI) relevant to
      peptide quantitative structure--activity relationship (QSAR) studies. These
      features are derived from optimized three-dimensional structures of the natural
      and unnatural amino acids. Since the descriptors are derived considering side
      chain three-dimensional structure, 3D-QSARs result. Using the method of partial
      least squares, 3D-QSARs of peptide sets were developed. A comparison of the
      results to those obtained with the principal properties or z-scales shows that
      the ISA and ECI are comparable for parameterizing the structural variability of
      the peptide series and represent an interesting alternative.

PMID- 7629812
TI  - Solid-state nuclear magnetic resonance analysis of the conformation of an
      inhibitor bound to thermolysin.
AB  - A number of structural experimental methods are available to determine the
      receptor-bound conformation of ligands as part of the process of rational drug
      design, including X-ray diffraction and solution-state NMR. Not all
      receptor/ligand systems are amenable to these types of analyses due to
      difficulties in sample preparation or inherent limitations of the methods.
      Rotational echo double-resonance (REDOR) NMR is a solid-state, magic angle
      spinning technique that measures the dipolar coupling between specifically
      labeled nuclei and enables the determination of internuclear distance. In
      previous studies of helical peptides, we have verified the ability of REDOR NMR
      to measure distances accurately and precisely. In this study we use REDOR and
      double REDOR to measure distances between backbone atoms in a phosphonamidate
      transition-state inhibitor bound to thermolysin. The 31P-13C', 31P-15N, and 31P
      13C alpha distances (3.61 +/- 0.10, 3.89 +/- 0.12, and 5.37 +/- 0.13 A,
      respectively) measured in a complex of Cbz-GlyP-[1-13C]Leu-[15N,2-13C]Ala and the
      enzyme are consistent with those observed by X-ray diffraction in other
      comparable thermolysin/inhibitor complexes (average values of 3.58 +/- 0.04, 3.91
      +/- 0.13, and 5.17 +/- 0.18 A, respectively). These results demonstrate that
      REDOR NMR is a viable alternative to more traditional methods such as X-ray
      diffraction, transferred NOESY, and isotope-edited NOESY for characterizing the
      receptor-bound conformation of ligands.

PMID- 7629811
TI  - Novel angiotensin II receptor antagonists. Design, synthesis, and in vitro
      evaluation of dibenzo[a,d]cycloheptene and dibenzo[b,f]oxepin derivatives.
      Searching for bioisosteres of biphenylyltetrazole using a three-dimensional
      search technique.
AB  - Three-dimensional substructure searching (3D search), using the program MACCS-3D,
      was utilized for designing novel angiotensin II receptor antagonists which
      contain a bioisostere of the biphenylyltetrazole moiety of DuP 753. A 3D query
      was prepared from an overlay model of substructures of several potent AII
      antagonists. The search system retrieved 139 compounds from the database MDDR-3D,
      which consisted of 29,400 medicinal patent compounds. A tricyclic compound was
      selected from the retrieved compounds and then evolved by considering steric
      fitness to the overlay model and synthetic feasibility. Finally, various novel
      AII antagonists having dibenzo[a,d]cycloheptene or dibenzo[b,f]oxepin were
      designed and synthesized. The receptor binding activity (Ki) for several members
      of this series was in the 10(-10) M range, demonstrating the ability of 3D search
      technique to explore new lead structures.

PMID- 7629813
TI  - Reversible inhibitors of the gastric (H+/K+)-ATPase. 4. Identification of an
      inhibitor with an intermediate duration of action.
AB  - 3-Acyl-4-(arylamino)quinolines were previously identified as gastric (H+/K+)
      ATPase inhibitors, and clinical efficacy has been demonstrated for compound 3
      (SK&F 96067). In the present study the further structure-activity relationship of
      this series is developed. Only a limited range of substituents are tolerated on
      the N-aryl ring or the 6- and 7-positions of the quinoline, and although
      hydroxylated derivatives were identified possessing markedly greater affinity for
      the enzyme, none of these proved to have adequate potency after oral dosing. In
      contrast, the 8-position of the quinoline ring proved suitable for a wide variety
      of substituents, allowing modification of physicochemical properties while
      retaining primary activity. This led to the identification of compound 4 (SK&F
      97574), which combines good oral potency with a somewhat longer duration of
      action than 3 (though much shorter than covalent inhibitors such as omeprazole).
      This compound was selected for further development and evaluation in man.

PMID- 7629814
TI  - Reversible inhibitors of the gastric (H+/K+)-ATPase. 5. Substituted 2,4
      diaminoquinazolines and thienopyrimidines.
AB  - Quinazolines bearing a secondary 4-(arylamino) substituent demonstrate an SAR for
      inhibition of the gastric (H+/K+)-ATPase different from the previously described
      3-acylquinolines, suggesting that, although these compounds are also K(+)
      competitive, they probably bind to the enzyme in a different orientation.
      Compounds bearing a tertiary 4-(arylamino) substituent, however, in particular 4
      (N-methylarylamino), appear to possess an SAR quite similar to the 3
      acylquinolines. We show that this arises from the effect of the N-methylation,
      which is to orientate the 4-(arylamino) substituent syn to C5, analogous to the 3
      acylquinolines. Compounds possessing both a 4-(N-methylarylamino) substituent and
      a 2-(arylamino) substituent proved to be very potent, K(+)-competitive inhibitors
      of K(+)-stimulated ATPase activity with Ki values down to 12 nM. Some compounds
      also proved to be effective inhibitors of stimulated acid secretion in both the
      rat and dog when dosed intravenously. However, although a number of these
      demonstrated activity after oral administration in the dog, the level and
      variability precluded further evaluation.

PMID- 7629815
TI  - 11 beta-substituted estradiol derivatives. 2. Potential carbon-11- and iodine
      labeled probes for the estrogen receptor.
AB  - Four new classes of 11 beta-substituted estradiol and estriol derivatives
      (cyanoalkyl, ethynyl, propynyl, and iodovinyl) have been synthesized, and their
      binding affinity for the estrogen receptor has been evaluated. The binding
      affinity values indicate that the estrogen receptor has tolerance for estradiol
      derivatives bearing 11 beta-groups whose size, rigidity, and polarity are
      limited. The estradiol derivatives have higher affinity than the estriol
      derivatives. The potential of these agents as imaging agent for estrogen receptor
      positive breast tumors is discussed. On the basis of the results of this and a
      previously reported study (Napolitano, E.; Fiaschi, R.; Carlson, K. E.;
      Katzenellenbogen, J. A. 11 beta-Substituted Estradiol Derivatives, Potential High
      Affinity Carbon-11-Labeled Probes for the Estrogen Receptor: A Structure-Affinity
      Relationship Study. J. Med. Chem. 1995, 38, 429-434), a general strategy for
      designing high-affinity probes for the estrogen receptor is proposed.

PMID- 7629816
TI  - [(Biaryloxy)alkyl]isoxazoles: picornavirus inhibitors.
AB  - A series of biphenyl analogs, 6, of 5-[5-(2,6-dichloro-5-oxazolylphenoxy)pentyl]
      3-methylisoxazole (2) have been synthesized and tested in vitro against 10 human
      rhinovirus serotypes in a TCID50 assay. The most potent compound in the series
      6s, 3-[3-[2,6-dimethyl-4-(4-fluorophenyl)-phenoxy]propyl]-3-methylisoxazole , was
      screened against an additional 84 serotypes. It was found to be active against 64
      of the serotypes, while 87 serotypes were sensitive to 2 at < 3 micrograms/mL. On
      comparison of the active serotypes, 6s exhibited greater potency versus 2.
      Analogs 6a-c,s were examined for in vitro metabolic stability by monkey liver
      microsomal assay. These analogs exhibited a greater than 7-fold improvement (t1/2
      > 200 min) in metabolic stability compared with 2 (t1/2 > 27 min).

PMID- 7629817
TI  - Synthesis, pharmacologic activity, and structure-activity relationships of a
      series of propafenone-related modulators of multidrug resistance.
AB  - A series of [(o-acylaryl)oxy]propanolamines have been prepared and evaluated for
      multidrug resistance-reverting activity in a human tumor cell model. Structure
      activity relationship studies indicate that the phenylpropiophenone moiety as
      well as the substitution pattern at the nitrogen atom is crucial for activity of
      the compounds. Incorporation of the ether oxygen into a benzofuran substructure,
      which renders the compound an arylethanolamine, decreased biologic activity.
      Highest activity could be observed with the arylpiparazines 4f-h, which not only
      completely restored daunomycin sensitivity but also showed moderate activity in
      restoring etoposide toxicity.

PMID- 7629818
TI  - Synthesis and pharmacological evaluation of 2'-hydroxychalcones and flavones as
      inhibitors of inflammatory mediators generation.
AB  - 2'-Hydroxy-3,4-dimethoxy-3',4'-dimethylchalcone (3a), 2'-hydroxy-3',4',3,4
      tetramethoxychalcone (3b), and their corresponding flavones, 3',4'-dimethoxy-7,8
      dimethylflavone (4a) and 3',4',7,8-tetramethoxyflavone (4b), were prepared from
      3,4-dimethoxycinnamic acid and the respective phenol. The four compounds
      inhibited enzymic lipid peroxidation and showed weak peroxyl scavenging activity.
      They also reduced LTB4 release from human neutrophils stimulated by A23187. The
      chalcone 3b was the only compound able to inhibit in a concentration-dependent
      way, synovial human recombinant phospholipase A2 activity, human platelet TXB2
      generation, and human neutrophil degranulation. This chalcone exerted topical
      antiinflammatory effects in mice.

PMID- 7629819
TI  - [Cholecystectomies at the Saint-George Hospital. Apropos of 672 operations
      performed, 1982-1991].
AB  - In a retrospective study of a 10-year period (1982-1991), the results of 672
      consecutive operations for cholecystectomy were analyzed. 67.7% were females and
      the medium age was 54.4%. Ultrasound is used to be the test of choice and surgery
      was done for chronic cholecystitis in 79.9% and in 20.1% for acute cholecystitis.
      With an overall mortality rate of 1.9% and a morbidity of 16%, conventional
      cholecystectomy proved to be a safe method. Mortality and morbidity seem to be
      related to age (> 60 years, median age 70.5), sex (men = 70%), and associated
      procedures (choledochotomy with exploration, sphincterotomy, biliary derivation).
      Systematic antibiotic prophylaxis and non drainage of the sub-hepatic area in
      certain cases lowered the incidence of wound infection, and improved post
      operative course. Selective operative cholangiogram also improved per and post
      operative course and does not seem to increase the incidence of residual stones.
      Now, only the new laparoscopic cholecystectomy may represent the alternative to
      the ideal treatment of cholecystolithiasis.

PMID- 7629820
TI  - [Percutaneous central venous catheters in neonatal intensive care. Personal
      experience].
AB  - The authors describe their own experience about using a siliconed percutaneous
      central venous catheter in the newborn, experience performed in their neonatal
      intensive care unit in Beirut. The technique consists in introducing this sort of
      device centrally by using a peripheral vein. The authors performed a prospective
      study on thirty-two newborns: Their results seem to indicate, in accordance to
      the literature review, that this technique offers many advantages such as sparing
      the newborn veins, prolonged hyperalimentation and treatment, and less incidents
      than the other perfusion techniques (peripheral and central). Few inconveniences
      are encountered: limitation of the amount of daily perfusion, impossibility of
      transfusing blood or derivatives across the silicone catheter.

PMID- 7629821
TI  - Physical exercise in the management of hypertension. World Hypertension League.

PMID- 7629822
TI  - [Constrictive pericarditis after aortocoronary bypass. Apropos of a case].
AB  - We report a case of pericarditis following aorto-coronary by-pass surgery which
      gradually developed into chronic constrictive pericarditis. The disease was a
      long time ignored because symptoms are not specific. In our case the clinical
      presentation looked like a cirrhosis especially that our patient developed an
      hepatitis after blood transfusion. In this occasion criteria of diagnostic are
      reminded. Hemodynamic investigation is still the best method of diagnosis and the
      only treatment is surgical and consists of pericardial decortication.

PMID- 7629823
TI  - Total anomalous pulmonary venous connection in adults--a surgical review.
AB  - The authors report a case of surgical repair of total anomalous pulmonary venous
      connection in a 36-year-old male. This is a very rare disease in adulthood since
      over 80% of the infants die before one year of age. Fifty-two surgical cases were
      previously reported in the literature. An extensive review of these cases is
      presented. Surgery is the only treatment and offers excellent short- and long
      term results.

PMID- 7629824
TI  - [Pregnancy in a woman with mechanical mitral prosthesis: apropos of a case
      treated with intravenous heparin until delivery].
AB  - Pregnancy with mechanical mitral prosthesis poses several risks either for the
      fetus and the mother. A good care including the contribution of an obstetrician,
      a cardiologist, an anesthesiologist and a neonatologist is strongly recommended
      during pregnancy until delivery. The anticoagulation causes a major risk. The
      heparin may be given during the whole pregnancy or may be replaced by the oral
      anticoagulants from the 13 weeks of last menstrual period until 10 to 15 days
      before delivery. Considering the difficulty to have an adequate anticoagulation
      with subcutaneous heparin, we have tried in ambulatory with our patient the
      intravenous heparin under a strict observation.

PMID- 7629825
TI  - [Digestive manifestations of juvenile dermatomyositis. A case report and review
      of the literature].
AB  - Childhood dermatomyositis should be separated from the adult polymyositis and is
      characterized by the frequency of vasculitis and ulcerations of the
      gastrointestinal tract. The authors present a case of colonic perforation with a
      review of the different disorders of the gastrointestinal system secondary to
      this disease.

PMID- 7629826
TI  - Cancer pain: pharmacological management (Part Two).

PMID- 7629827
TI  - Ibn Zuhr [Avenzoar] (1091-1162).

PMID- 7629829
TI  - [Writing the operative report].

PMID- 7629828
TI  - Management of hemorrhoids by rubber band ligation.
AB  - This study discusses the management of hemorrhoids by rubber band ligation. It
      reviews 233 rubber band ligation procedures in 148 patients with symptomatic
      hemorrhoids performed over a 5-year period. 72% of the patients underwent a
      single rubber band ligation, 22% a double band ligation and 6% a triple band
      ligation in one session without anesthesia. A follow-up of 18 +/- 5 months was
      carried out. Only three patients required hospitalization for complications. One
      patient was admitted for bleeding and recovered with clot evacuation, bed rest
      and blood transfusion. Two patients developed a band related abscess that
      resolved with drainage. Twenty patients (13.5%) reported pain associated with the
      procedure. Four patients needed subsequent surgical hemorrhoidectomy. Long-term
      results were good in 81.2% of the patients. This report agrees with previously
      published series showing the efficacy and cost containment of hemorrhoidal
      ligation.

PMID- 7629830
TI  - Concept of cardiovascular remodeling and cardioreparation.

PMID- 7629831
TI  - Breast cancer: guidelines for modern management.

PMID- 7629832
TI  - [Gynecologic endoscopic surgery at Saint-Charles Hospital. Review of the
      literature].
AB  - In this study we present 41 cases of endoscopy surgery in gynecology done in
      Saint Charles Hospital for: extra-uterine pregnancies (GEU), pelvic abscess,
      pelvic endometriosis, ovarian cysts (KO), polycystic ovaries (PKO), primary
      amenorrhea, postoperative pelvic adhesions, uterine fibroma and appendicitis.
      These patients consulted for infertility, irregular menses and pelvic pain. The
      procedures done were the following: salpingectomy, endo-tubal aspiration, pelvic
      abscess drainage and IUD removal, endometrial implants coagulations, excision of
      ovarian cysts, multiple ovarian punctures (MPO), wedge resection of ovaries,
      ovarian biopsies, adhesiolysis, myomectomies, hysterectomies and appendectomies.
      The final results and smooth post-operative course are in favour of the technical
      and therapeutic advantages of the endoscopic surgery in gynecology as a
      conservative, functional and preventive procedure.

PMID- 7629833
TI  - [Transesophageal ultrasonography, technique, indications, limits].

PMID- 7629834
TI  - Cancer in Lebanon. An update of epidemiological data.

PMID- 7629836
TI  - Spontaneous regression of malignant lymphoma. Case report and review of the
      literature.
AB  - This article reports on an exceptional case of spontaneous regression of a
      malignant lymphoma of intermediate type with three localizations in the same
      patient. A review of the literature concerning the immunologic approaches to
      cancer have been considered and attempts to explain the host response to
      neoplasms and its defense mechanisms against them, were considered.

PMID- 7629835
TI  - [Silicone implants and breast cancer: real or fictitious problem? A case report
      and review of the literature].
AB  - We present a case of breast cancer 9 years after subcutaneous mastectomy for
      bilateral phylloid tumor with silicone implants. The patient had a stage III
      adenocarcinoma (T4 N1 M0) at diagnosis; a modified radical mastectomy was done,
      followed by radiotherapy and chemotherapy. Later on, Tamoxifen was prescribed
      (positive hormone receptors). Reviewing the literature about this subject in a
      context of a moratorium of the Food and Drug Administration (FDA) in the United
      States recommending suspension of silicone breast implantation, we can propose
      several conclusions: Previous and recent studies did not show any direct relation
      between cancer and silicone implants for augmentation mammoplasty; on the
      contrary, a lower incidence of breast cancer is noted. Breast cancer incidence
      with silicone implants seems to be higher with reconstructive mammoplasty after
      mastectomy for benign disease (fibrocystic disease, dysplasia, phylloid tumor),
      or prophylactic reason, or malignancy (carcinoma in situ, lobular and multifocal
      carcinoma, early breast cancer...). This can be related to recurrence or cancer
      development on residual breast tissue. Breast cancer with silicone implants is of
      poorer prognosis because of the later diagnosis of the disease.

PMID- 7629837
TI  - [Can thrombolysis be done on patients needing cardiopulmonary resuscitation
      during the acute phase of a myocardial infarction?].

PMID- 7629838
TI  - Ibin Zuhr's contribution to surgery.

PMID- 7629839
TI  - [Primary angioplasty at the stage of acute myocardial infarction].
AB  - The success of thrombolytic therapy for acute myocardial infarction is limited by
      failure of reperfusing 25% of occluded arteries, bleeding complications in 0.4 to
      1% of patients and the possibility of recurrent ischemia. These problems can be
      overcome by the use of immediate angioplasty without previous thrombolytic
      therapy. Between February and December 1993, twelve patients (ten men and two
      women) admitted for acute myocardial infarction were treated by immediate
      angioplasty. Five patients had a contraindication to thrombolysis and seven had
      angioplasty as a deliberate choice. Successful recanalisation was obtained in 11
      patients (92%) with one reocclusion at 24 hours. Two patients admitted in
      cardiogenic shock 12 hours after the onset of symptoms died lately with
      multiorgan failure. Only one case of clinical restenosis was observed and was
      redilated. In conclusion, immediate angioplasty without prior thrombolytic
      therapy is a rapid method of revascularisation with minimal risk and good outcome
      when it is used early after acute myocardial infarction.

PMID- 7629840
TI  - Microsurgical high inguinal varicocelectomy with delivery of the testis.
AB  - This study describes the results of 50 consecutive cases of varicocelectomy by
      the inguinal approach. The testicle is delivered through a small inguinal
      incision, and all external spermatic and gubernacular veins are ligated. The
      testis is returned to the scrotum and the spermatic cord is dissected under
      optical magnification. The testicular artery, the lymphatics and the vas deferens
      are identified and preserved. All internal spermatic veins are ligated. 94
      varicocelectomies were performed in 50 men. Follow-up period extended from 12
      months to 24 months. No hydroceles, no clinical recurrences and no wound
      infection were found. One scrotal hematoma occurred and resolved progressively.
      Preoperative and postoperative semen analysis were obtained. The changes in sperm
      count mean value (million/cc) (20 to 28.6) (p < 0.005), per cent normal forms
      (42.9 to 52.1%) (p < 0.005) and per cent motility (31.5 to 39.2%) (p < 0.005)
      were significant. The pregnancy rate was 10 of 21 couples available for follow-up
      (47.6%). This technique results in a significant decrease in the incidence of
      hydrocele formation, testicular artery injury and varicocele clinical recurrence.

PMID- 7629841
TI  - [Augmentation cystoplasty and intermittent catheterization in neurogenic
      bladder].
AB  - An enterocystoplasty was done on 17 paraplegic adults patients (Beit Chahab
      Hospital for Handicapped) with hyperreflexic neurogenic bladder secondary to an
      accident of the supra-sacral medulla. These patients were incontinent, had
      urinary tract infections, vesico-renal reflux or autonomic dysreflexia.
      Detubularized ileum was used in 16 cases and sigmoid in one. Ureteral
      reimplantation was performed on one patient; implantation of an artificial
      urinary sphincter for one patient and an injection of a periurethral Teflon paste
      was also done for one patient. After 16 months of follow-up all patients are
      continent on self intermittent catheterization. The upper urinary tract is stable
      or improved. No autonomic dysreflexia. Thirteen patients have an asymptomatic
      untreated bacteriuria.

PMID- 7629842
TI  - Microsurgical composite tissue transfer: an expanding horizon in reconstructive
      surgery.
AB  - Seven cases of microsurgical composite tissue transfer to reconstruct defects of
      the upper and lower extremities performed at the American University of Beirut
      Medical Center between January 1992 and July 1993 are evaluated in a
      retrospective study. These cases illustrate the various clinical situations where
      free flaps can be used to an advantage. A brief discussion of the history of
      microvascular free flap transfers as well as their value in modern plastic and
      reconstructive surgery is also presented.

PMID- 7629844
TI  - Conservative surgical treatment of 27 cases of umbilical pilonidal sinus.
AB  - A retrospective study of 27 cases of umbilical pilonidal sinus (UPNS) was
      conducted at the Central Military Hospital of Beirut between 1987 and 1991. In
      this study a simple conservative surgical technique is described by removing the
      dead hair and the cotton like dirt as an outpatient procedure without need for
      anaesthesia or hospitalization. There were 26 male and one female, a mean age of
      26 years, patients were followed for a period of 2 years (1987-1991). The cure
      rate was 98% with only four cases which needed more than one session of
      treatment.

PMID- 7629843
TI  - [Infections in cancer patients with granulocytopenia. Retrospective studies of 59
      febrile episodes with hospitalization].
AB  - A total of 59 febrile neutropenic episodes were retrospectively recorded at Hotel
      Dieu de France Hospital between August 1st 1991 and December 31st 1992. These
      episodes were recorded in 51 cancer patients. Median neutropenia was less than
      one week in 50% of the cases. The etiology of these fever was documented in 27
      episodes (46%) and in 70% of the cases gram (-) rods were documented. B-Lactam
      and Aminoglycoside antibiotics were used in 34 episodes at the initial treatment
      of these patients. Success rate at this initial treatment or with a modification
      of the antibiotic therapy was recorded in 85% of the patients. Only 15% of the
      patients failed to this antibiotherapy, 2/3 of them had their disease in
      progression. The systemic use of Amphotericine E in those patients with prolonged
      febrile neutropenia and the concommitent use of growth factors in a sub-group of
      patients at high risk could lead to a higher success rate in these patients.

PMID- 7629845
TI  - Tuberculosis: resurging disease with new dimensions--current status and new
      trends in laboratory diagnosis.

PMID- 7629846
TI  - [Nutrition and cancer].

PMID- 7629847
TI  - Economics of hypertension control.

PMID- 7629848
TI  - [Control of health expenditures and quality of health care].

PMID- 7629849
TI  - Spontaneous intraperitoneal rupture of the bladder.
AB  - Spontaneous intraperitoneal rupture of the bladder (also called unsuspected,
      idiopathic, or non-traumatic rupture of the bladder) is a well defined but rare
      condition which has not been universally recognized in the past. We are reporting
      four cases and emphasizing its clinical picture so it might be better recognized
      and diagnosed early on in the process, and so that its management be planned
      appropriately in order to reduce its morbidity and its mortality. A review of the
      literature is provided to help achieve this end. Spontaneous intraperitoneal
      vesical rupture is almost always a surprise at laparotomy. A high degree of
      suspicion, the finding of urea in the ascitic fluid, and cystography may help in
      the diagnosis. Symptoms include abdominal pain, difficulty in micturition,
      hematuria and renal failure with elevation of the blood urea and acidosis. The
      etiology seems to be varied and somehow confused. We discuss four groups of
      etiological factors: dulled sensorium, weakening of the bladder wall, increased
      intra-vesical pressure (with or without bladder outlet obstruction) and vascular
      lesions (radiotherapy, arterial embolism and vesical infarction); and we try to
      discern common denominators for these four groups of etiological factors: an
      increase in intravesical pressure along with a weakening of the bladder wall.
      Finally the new concept of vesical infarction following ischemia due to
      overdistention of the bladder is introduced and discussed.

PMID- 7629850
TI  - Evaluation of the polymerase chain reaction for early diagnosis of leptospirosis.
AB  - Early diagnosis of leptospirosis is important because severe leptospiral
      infection can run a fulminant course. The polymerase chain reaction (PCR) was
      evaluated for the detection of leptospires in clinical samples from patients with
      acute leptospiral infection. Blood and urine samples from 71 patients with
      leptospirosis were examined by PCR, culture or serology. Samples from 44 (62%)
      patients with the diagnosis of leptospirosis were positive by PCR as compared to
      34 (48%) by culture. The presence of leptospires was demonstrated by PCR in 13
      patients before the development of antibodies, as well as in two patients who
      were seronegative during their illness and at autopsy. Samples from 16 patients
      without leptospirosis were seronegative and culture negative, and also negative
      by PCR. We conclude that PCR is a rapid, sensitive and specific means of
      diagnosing leptospiral infection, especially during the first few days of the
      disease.

PMID- 7629851
TI  - The elucidation of novel capsular genotypes of Haemophilus influenzae type b with
      the polymerase chain reaction.
AB  - Molecular characterization is an important pre-requisite for post-vaccine studies
      of Haemophilus influenzae type b (Hib). Three capsular genotyping patterns, b(S),
      b(G) and b(V), have been described in the major phylogenetic lineage of Hib.
      However, in a recent series of prospective studies, three new hybridisation
      patterns were observed among 425 strains of Hib. Four pairs of polymerase chain
      reaction (PCR) primers were used to identify the capsular gene (cap) structure of
      these Hib strains. This showed that the strains possessed simple DNA re
      arrangements. In two instances a change in restriction enzyme recognition site
      was the most likely cause of the new hybridisation pattern. The third strain
      possessed a cap b locus consisting of intact tandem repeats of cap b in a b(S)
      background. It was reasoned that a similar cap b locus would not be readily
      recognised by hybridisation in a b(G) background, and b(G) strains were therefore
      characterized by the PCR method. This showed one of 35 b(G) strains to possess a
      cap locus with intact tandem repeat copies of cap b. The novel capsular genotypes
      described here are rare, but can be detected rapidly and accurately by a
      combination of PCR and capsular genotyping hybridisation patterns.

PMID- 7629852
TI  - Bovine mastitis caused by Listeria monocytogenes: characteristics of natural and
      experimental infections.
AB  - Experimental mastitis induced with a single intramammary injection of Listeria
      monocytogenes was compared with two naturally occurring cases. Four strains of L.
      monocytogenes, two of serotype 1/2a and two of serotype 4b were used for the
      experimental infections and two diametrically opposed quarters of four cows were
      inoculated with 300 cfu. Bacteriological examination and somatic cell counts of
      quarter foremilk samples were performed weekly for at least 6 months after
      challenge. All the inoculated quarters developed chronic subclinical mastitis
      with occasional clinical episodes. The results were similar to those observed in
      natural listeria mastitis. Four experimentally infected quarters were treated
      during lactation (gentamicin and cloxacillin) or at "drying-off" (cloxacillin),
      or at both times. Only one of four quarters was cured after treatment only at
      "drying-off". All experimental and naturally infected animals were slaughtered
      and bacteriological examination was performed on liver, spleen and supramammary,
      iliac and mesenteric lymph nodes. L. monocytogenes strains were isolated from the
      supramammary lymph nodes of two experimentally and two naturally infected cows
      and from an iliac lymph node from one of the naturally infected cows. The
      epidemiological data were supported by serotyping, lysotyping and DNA macro
      restriction analysis. The experimental model of listeria mastitis mimics
      spontaneous cases and should be useful in further studies of listeria mastitis.

PMID- 7629853
TI  - Adhesion of staphylococci to polyurethane and hydrogel-coated polyurethane
      catheters assayed by an improved radiolabelling technique.
AB  - Adhesion of Staphylococcus epidermidis NCTC 11047 to the external surface of
      polyurethane catheters was quantified by a radiolabelling assay. Maximum adhesion
      was achieved with an initial cell concentration of 3 x 10(8)/ml after incubation
      for 120 min. The assay was tested for reproducibility by analysis of variance.
      Adhesion of clinical strains of S. epidermidis and S. aureus to uncoated
      polyurethane and hydrogel (Hydromer)-coated polyurethane catheters was compared.
      Hydrogel coating significantly reduced adhesion for both S. epidermidis and S.
      aureus (mean percentage reduction 71% for S. epidermidis, 69% for S. aureus).
      Clinical isolates were also tested for adhesion to polystyrene by a modified
      microtitration well adhesion assay; there was no correlation between
      staphylococcal adhesion to polyurethane catheters and adhesion to polystyrene.
      Cell surface hydrophobicity values varied widely for both species. Positive
      correlations were found between cell surface hydrophobicity and adhesion to
      polystyrene and uncoated polyurethane catheters for S. epidermidis but not for S.
      aureus.

PMID- 7629854
TI  - A protective role for lymphocytes in cyclophosphamide-induced endogenous
      bacteraemia in mice.
AB  - Cyclophosphamide (CY) is used in many animal studies, including models of
      bacteraemia, to deplete peripheral neutrophils and induce a compromised state.
      Although CY also influences lymphocyte function, the protective role of
      lymphocytes in bacteraemia is unclear. Therefore, CY (200 mg/kg) was administered
      to ddY mice and its influence on the number, cellular composition, and function
      of lymphocytes in the spleen and Peyer's patches was examined. A single dose of
      CY reduced the number of lymphocytes in a time-dependent fashion. Flow cytometry
      showed that B cells carrying B220 antigen decreased significantly. The production
      of IgA in Peyer's patches, as measured by enzyme-linked immunosorbent assay, was
      also suppressed in a time-dependent fashion. Blastogenic responses of splenic
      lymphocytes to Concanavalin-A, lipopolysaccharide and heat-killed Pseudomonas
      aeruginosa were suppressed 48 h after CY administration. The results suggest that
      CY suppresses the number and function of lymphocytes, especially B cells. This
      may lead to bacterial overgrowth in the gut and result in bacteraemia.
      Intravenous transfusion of normal lymphocytes or oral inoculation of IgA to mice
      with P. aeruginosa D4 endogenous bacteraemia significantly increased survival
      rates, indicating that lymphocytes and their products have a protective role in
      bacteraemia in mice.

PMID- 7629855
TI  - A numerical taxonomic study of the gram-positive anaerobic cocci.
AB  - Clinical (101) and collection (26) strains of gram-positive anaerobic cocci were
      examined in conventional tests and pyrolysis mass spectrometry (PMS). Numerical
      classifications based upon conventional test reaction patterns (CTRPs) and PMS
      showed 27 and 22 clusters, respectively. Cross-tabulation of cluster membership
      in the two classifications showed excellent correlation, with the combined
      classifications showing clear groups corresponding to the currently recognised
      species Peptostreptococcus anaerobius, P. heliotrinreducens, P. hydrogenalis, P.
      indolicus, P. lactolyticus, P. magnus, P. micros and Peptococcus niger. Strains
      of P. prevotii and P. tetradius clustered together in a heterogeneous group of
      saccharolytic organisms. However, strains previously identified as P.
      asaccharolyticus were divided into three distinct groups in PMS, two of which
      differed only in indole-associated pyrolysis products. A further four groups and
      several single-member clusters were distinct from these species. PMS data
      supported the validity of identification by pre-formed enzyme profiles and
      confirmed that Hare group III is synonymous with P. hydrogenalis, Hare group IV
      with P. magnus, and the "ADH group" with P. vaginalis. There is clearly a need
      for a taxonomic revision of the genus Peptostreptococcus, which probably
      encompasses several generic groups.

PMID- 7629856
TI  - Demonstration of Mycobacterium kansasii species heterogeneity by the
      amplification of the 16S-23S spacer region.
AB  - Amplification of the region separating the genes coding for the two rRNA species
      16S and 23S was performed with 56 strains of several mycobacterial species,
      including 21 clinical isolates of Mycobacterium kansasii and the M. kansasii type
      strain ATCC 12478. On the basis of PCR product profiles, the previously suggested
      heterogeneity of M. kansasii species was confirmed. Three subgroups were
      identified; members of the first subgroup showed the same PCR profile as the
      reference strain. Different profiles were obtained for the two other subgroups.
      Amplification of the 16S-23S spacer is rapid and simple and, consequently, may be
      a helpful tool for identification and characterisation of M. kansasii isolates in
      epidemiological analysis.

PMID- 7629857
TI  - Human papillomaviruses and the genital tract: old virus, new developments.

PMID- 7629858
TI  - Tuberculosis and AIDS.
AB  - Since the mid-1980s, the rate of decline in reported cases of tuberculosis (TB)
      has reached a plateau or reversed because of a combination of poverty and
      increased homelessness, immigration and displacement, poorly managed and supplied
      TB control programmes and, particularly in the developing world, the emergence of
      human immunodeficiency virus (HIV) infection. TB in HIV-positive patients may
      present atypically, both clinically and radiologically, with a lower probability
      of sputum positivity, greater difficulty in diagnosis, and a more rapid clinical
      deterioration than TB in HIV-seronegative patients. The emergence of multiple
      drug-resistant strains of Mycobacterium tuberculosis, particularly in patients
      infected by HIV, carries a high mortality and has been associated with outbreaks
      in Europe and the USA. Microscopy and culture form the basis of diagnosis, but
      there is a need for more rapid diagnostic techniques and novel methods of drug
      susceptibility testing. Prolonged supervised treatment programmes and the
      development of new chemotherapeutic agents and regimens are essential
      prerequisites for successful TB therapy in AIDS patients. This review examines
      the clinical, microbiological and epidemiological issues associated with TB in
      HIV-infected individuals.

PMID- 7629859
TI  - Bacteroides infections in children.
AB  - From 1974 to 1990, 336 Bacteroides isolates were obtained from 312 specimens from
      274 patients. They comprised 180 (54%) B. fragilis isolates, 55 (16%) B. theta
      iotaomicron, 36 (11%) B. vulgatus, 34 (10%) B. distasonis, 21 (6%) B. ovatus and
      10 (3%) B. uniformis. Infections in 253 (92%) patients were polymicrobial, but in
      21 (8%) children, a Bacteroides sp. was isolated in pure culture. Most
      Bacteroides isolates were from peritoneal fluid (114), abscesses (110), wound
      infections (20), blood cultures (10) and from patients with pneumonia (14) or
      chronic otitis media (8). Predisposing conditions were present in 145 (53%)
      children; these were previous surgery (46), trauma (28), malignancy (21),
      prematurity (19), immunodeficiency (18), steroid therapy (12) foreign body (10),
      diabetes (9) and sickle cell disease (7). The micro-organisms isolated most
      commonly mixed with Bacteroides spp. were anaerobic cocci (221), Escherichia coli
      (122), Fusobacterium spp. (38) and Clostridium spp. (30). All patients received
      antimicrobial therapy in conjunction with surgical drainage or correction of
      pathology in 197 (72%) cases. All but 12 (5%) patients recovered. These data
      illustrate the importance of Bacteroides spp. in infections in children.

PMID- 7629860
TI  - Immunological detection of Bacteroides fragilis in clinical samples.
AB  - A monospecific polyclonal antiserum, prepared against Bacteroides fragilis common
      polysaccharide antigen purified by polyacrylamide gel immunoblot detected B.
      fragilis, B. thetaiotaomicron, B. ovatus and Prevotella melaninogenica in pus
      samples from various anatomical sites by immunofluorescence microscopy of the
      pus. With standard clinical laboratory culture methods, 36% of 147 samples were
      positive for one or more of the above bacteria. Of these, B. fragilis accounted
      for 33%. By immunofluorescent labelling of pus with the common antigen antiserum
      the detection of these bacteria in the samples increased to 50%. All nine of the
      blood cultures in which B. fragilis was detected by culture contained bacteria
      positive for the common antigen. Immunofluorescent labelling of pus samples with
      a selection of monoclonal antibodies specific for surface polysaccharides which
      are known to be antigenically variable in culture in vitro and in an animal model
      of infection showed that these polysaccharides are also variable in natural
      infection. The results indicate that the common polysaccharide antigen, in
      contrast to the variable surface polysaccharides, is a suitable target for the
      immunodetection of B. fragilis in clinical samples from a range of anatomical
      sites.

PMID- 7629861
TI  - Trauma-induced degenerative changes in brain injury: a morphometric analysis of
      three patients with preinjury and postinjury MR scans.
AB  - Three patients with pretraumatic and posttraumatic brain injury (TBI) MR imaging
      of the brain are presented. Two patients had moderate to severe injury, whereas
      the third patient sustained a mild injury. Using imaging software to conduct
      morphometric analyses, quantitative neuropathologic change was ascertained in
      each TBI patient. Each case was compared quantitatively to preinjury scans as
      well as to an age-matched control group. For the moderately to severely injured
      patients, extensive degenerative changes were found throughout the various
      cortical structures and the cerebellum, whereas most midbrain and brainstem
      measures did not demonstrate significant change. For these two patients, the most
      significant changes occurred within the ventricular system, where generalized
      ventricular dilation was observed post-TBI. In the mild case, no significant
      anatomic changes were evident. These case studies demonstrate the use of
      quantitative methods for examining the structural basis of TBI sequelae.

PMID- 7629862
TI  - Hypothermia attenuates the normal increase in interleukin 1 beta RNA and nerve
      growth factor following traumatic brain injury in the rat.
AB  - Significant morbidity and mortality associated with traumatic brain injury (TBI)
      are allied with secondary posttrauma inflammatory complications. Hypothermia has
      been suggested as a possible treatment to lessen or suppress these inflammatory
      reactions. We report here that interleukin 1 beta, a cytokine responsible for
      initiating inflammatory cascades, is elevated in rat cortex within 6 h of TBI in
      the rat. Nerve growth factor (NGF) RNA and protein also increased subsequently,
      and NGF protein remained elevated for up to 7 days. Four hours of whole body
      hypothermia (32 degrees C), applied immediately after the TBI, attenuated the
      posttrauma increase in IL-1 beta RNA and eliminated the increase in NGF RNA and
      protein observed in cerebral cortex following TBI. Thus, hypothermia may be an
      effective therapy to diminish the posttrauma inflammatory cascade in the brain
      (as suggested by the decrease in IL-1 beta). However, the same treatment may
      hinder the brain's intrinsic repair mechanisms. Optimal treatment may, therefore,
      require supplemental administration of neurotrophic factors or other agents along
      with hypothermia.

PMID- 7629863
TI  - A model of parasagittal controlled cortical impact in the mouse: cognitive and
      histopathologic effects.
AB  - Controlled cortical impact (CCI), using a pneumatically driven impactor to
      produce traumatic brain injury, has been characterized previously in both the
      ferret and in the rat. In the present study, we applied this technique to
      establish and characterize the CCI model of brain injury in another species, the
      mouse, evaluating cognitive and histopathologic outcome. In anesthetized (sodium
      pentobarbital, 65 mg/kg) male C57BL mice, we performed sham treatment (no injury,
      n = 12) or CCI injury (n = 12) at a velocity of 5.7-6.2 m/sec and depth of 1 mm,
      using a 3-mm diameter rounded-tip impounder, positioned over the left
      parietotemporal cortex (parasagittal). At this level of injury, we observed
      highly significant deficits in memory retention of a Morris water maze task 2
      days following injury (p < 0.001). Postmortem histopathologic analysis performed
      at 48 h following injury revealed substantial cortical tissue loss in the region
      of impact and selective hippocampal neuronal cell loss in the CA2, CA3, and CA3c
      regions, using Nissl staining. Analysis of degenerating neurons using modified
      Gallyas silver staining techniques demonstrated consistent ipsilateral injury of
      neurons in the cortex adjacent to the impact site and in the dentate gyrus of the
      ipsilateral hippocampus. Bilateral degeneration was observed at the gray matter
      white matter interface along the corpus callosum. Glial fibrillary acidic protein
      (GFAP) immunohistochemistry revealed extensive reactive gliosis appearing
      diffusely through the bilateral cortices, hippocampi, and thalami at 48 h
      postinjury. Breakdown of the blood-brain barrier was demonstrated with antimouse
      IgG immunohistochemistry, revealing extravasation of endogenous IgG throughout
      the ipsilateral cortex, hippocampus, and thalamus. These results suggest that
      this new model of parasagittal CCI in the mouse mimics a number of well
      established sequelae observed in previously characterized brain injury models
      using other rodent species. This mouse model may be a particularly useful
      experimental tool for comparing behavioral and histopathologic characteristics of
      traumatic brain injury in wild-type and genetically altered mice.

PMID- 7629864
TI  - Superoxide dismutase improves posttraumatic cortical blood flow in rats.
AB  - Oxygen free radicals, such as the superoxide anion, are known to mediate damage
      to the cerebral microcirculation following traumatic brain injury. The purpose of
      this study was to determine if superoxide dismutase (SOD), a scavenger of
      superoxide anion, could alter posttraumatic cortical blood flow. Following
      barbiturate anesthesia, rats were surgically prepared for moderate fluid
      percussion brain injury. Cortical blood flow contralateral to the site of injury
      was measured using laser-Doppler flowmetry. Laser-Doppler flowmetry assesses flow
      by measuring cell volume and velocity, which are multiplied electronically to
      give flow. Starting 10 min before injury, animals received either superoxide
      dismutase (24,000 U/kg bolus, followed by continuous infusion of 1600 U/kg/min)
      or an equal volume of saline. Blood pressure, heart rate, and cortical blood flow
      were measured up to 1 h posttrauma. Rats receiving superoxide dismutase had
      significantly higher cortical blood flow posttrauma (F = 6.91, p < 0.02). One
      hour posttrauma, the blood flow in SOD-treated rats was 89 +/- 8% of preinjury
      baseline, whereas this value was only 66 +/- 6% of control in saline-treated
      rats. SOD caused not only greater blood velocity but also less reduction in
      cortical blood volume after injury. There were no significant differences between
      the groups with respect to blood pressure or heart rate. This study further
      supports the role of oxygen radical-mediated cerebrovascular dysfunction
      following traumatic brain injury and is the first to show the beneficial effect
      of SOD on cortical blood flow following fluid percussion brain injury.

PMID- 7629865
TI  - Immediate cerebrovascular responses to closed head injury in the rat.
AB  - Changes in cerebrovascular dynamics were investigated immediately after closed
      head injury in the rat using a newly developed closed head injury model developed
      by Marmarou et al. Intracranial pressure (ICP) and mean arterial blood pressure
      (MABP) were monitored before and after trauma. Regional cerebral blood flow
      (rCBF), regional cerebral plasma volume (rCPV), and blood-brain barrier (BBB)
      permeability were measured autoradiographically with iodo[14C]antipyrine
      [14C]sucrose, and [alpha-14C]aminoisobutyric acid, respectively. rCBF responses
      to induced hypertension after trauma were measured by laser-Doppler flowmetry to
      investigate the status of autoregulation. Before injury, baseline ICP values
      ranged from 6 to 10 mm Hg in all animals. Immediately after trauma, ICP increased
      synchronously with MABP to > 100 mm Hg and then rapidly returned to baseline
      values: MABP increased rapidly by 20% after trauma and returned to baseline
      values within 30 sec. At 30 sec after injury, a significant increase in rCBF was
      observed in five subcortical regions (p < 0.05), and a significant increase in
      rCPV was observed in the frontal cortex, parietal cortex, thalamus, and
      hypothalamus (p < 0.05). At 10 min after injury, BBB permeability (the transfer
      constant for [alpha 14C]aminoisobutyric acid) was < 0.1 mL/kg/min for all regions
      except those with a relatively permeable BBB, for example, median eminence,
      choroidal plexus, pineal body, and pituitary gland. Induced hypertension resulted
      in a prolonged increase in rCBF after trauma. Thus, in this closed head injury
      model, which is not associated with marked hypertension or prolonged BBB
      disruption, widespread increases in rCBF and impaired cerebral autoregulation
      were apparent immediately after injury.

PMID- 7629866
TI  - Dorsal spinal venous occlusion in the rat.
AB  - Occlusion of the major components of the spinal venous system is usually
      associated with spinal arteriovenous malformations or systemic thrombophlebitis.
      Although spinal venous system dysfunction has been implicated in compressive cord
      syndromes, myelopathies from decompression sickness, and spinal cord trauma, its
      pathophysiology remains unclear. To characterize disorders associated with spinal
      venous occlusion, we developed a model in the rat produced by focally coagulating
      the dorsal spinal vein transdurally at the T7 and T10 vertebral levels. Following
      such occlusion, venous stasis, sludging and perivascular hemorrhages in the small
      venous branches were observed. By 1 week postocclusion, animals developed
      hindlimb paralysis from which they partially recovered over time. Histologic
      examination in the acute phase disclosed tissue necrosis, edema, and hemorrhages
      predominantly in the dorsal aspect of the spinal cord. This was gradually
      replaced by an intense macrophagic infiltration and the partial formation of a
      cystic cavity by 1 month. These findings indicate that dorsal spinal vein
      occlusion in the rat causes significant neurologic and pathologic alterations. We
      conclude that this procedure produces a relevant animal model for the study of
      the pathophysiology of spinal venous occlusion, and it allows the
      characterization of its effects on spinal cord blood flow, the blood-spinal cord
      barrier, and the development of edema independent of cord compression. Our
      findings in this model provide an insight into one of the mechanisms of injury
      extension in spinal cord trauma and other disorders associated with spinal venous
      dysfunction.

PMID- 7629867
TI  - The temporal and spatial activation of microglia in fiber tracts undergoing
      anterograde and retrograde degeneration following spinal cord lesion.
AB  - The role of microglia in the response to CNS injury is not fully understood. We
      characterized the temporal activation of microglia in the adult spinal cord
      following a lesion that severed the axons of the dorsal columns and corticospinal
      tract at T8. Two days after lesion, microglia in the severed T4-T5 fasciculus
      (f.) gracilis were ameboid and expressed intense OX42 and increased class I major
      histocompatibility complex (MHC) antigen (OX18) immunoreactivities. No activated
      microglia were seen in the intact f. cuneatus or the corticospinal tract. Five
      days postlesion, OX42 immunoreactivity was slightly decreased in the f. gracilis,
      and OX18 expression was slightly enhanced. By 12 days postlesion, OX42 and OX18
      immunoreactivities were near control levels. At L1-L2, activated microglia with
      increased OX18 expression were restricted to the corticospinal tract and were
      maximal 5 days postlesion, returning to near control levels by 12 days
      postlesion. In the medulla, enhanced OX42 and OX18 immunoreactivities were seen
      in the nucleus (n.) gracilis, but not the n. cuneatus, at 2 days postlesion. At 5
      days postlesion, OX42 immunoreactivity was markedly decreased, but class I MHC
      antigen expression was still enhanced. GFAP immunoreactivity increased only in
      the n. gracilis and remained elevated 2-12 days postlesion. Microglial activation
      is an early lesion-induced event in the CNS, and activated microglia may play a
      role in mediating the regenerative capacity of injured CNS axons.

PMID- 7629868
TI  - Combination chemotherapy extends the therapeutic window to 60 minutes after
      stroke.
AB  - We sought to extend the therapeutic window for acute stroke therapy using the
      combination of a glutamate antagonist and a GABA agonist, which in prior studies
      was effective if given 5 min after stroke. We used a quantal bioassay to measure
      neuroprotective potency after injection of several thousand microspheres into the
      cerebral circulation of rats. The GABA-A agonist muscimol, but not MK-801, was
      effective if given 30, 45, or 60 min after embolization (potency ratio compared
      with saline of 3.0, 2.3, 1.8, respectively). If muscimol was combined with MK-801
      at lower doses of each drug, the combination was neuroprotective (potency ratio
      of 4.2). Agonists of GABA-A, but not GABA-B, receptors blocked the toxic
      vacuolization seen in the cingulate and retrosplenial cortex after MK-801
      treatment. Combination chemotherapy appears to extend the time window for acute
      stroke therapy in rats to 1 h and to result in fewer side effects.

PMID- 7629869
TI  - Effect of phenytoin on cortical Na(+)-K(+)-ATPase activity in global ischemic rat
      brain.
AB  - Na(+)K(+)-ATPase activity, water content, and Na+/K+ concentrations in the
      parietal cortex were measured in untreated and phenytoin-treated rats following
      global cerebral ischemia. Inhibitory effects of phenytoin treatment on brain
      edema and changes in Na(+)-K+ concentration with ischemia or ischemia followed by
      recirculation of varying intervals were assessed. The cortical Na(+)-K(+)-ATPase
      activity increased in the phenytoin-treated group during and after ischemia.
      Based on these results, we conclude that phenytoin provides ischemic brain
      protection by activating cortical Na(+)-K(+)-ATPase activity and by reducing
      intracellular Na+ and water content.

PMID- 7629870
TI  - Effect of human T-lymphotropic virus type I infection on non-Hodgkin's lymphoma
      incidence.
AB  - BACKGROUND: We previously reported from a case-control analysis that T-cell non
      Hodgkin's lymphoma (NHL) was strongly associated with human T-lymphotropic virus
      type I (HTLV-I) infection in Jamaica and Trinidad and that the relative risk for
      HTLV-I infection was very high in younger patients. PURPOSE: The objective of
      this study was to estimate the age-specific incidence rates of NHL among HTLV-I
      infected and HTLV-I-uninfected adults in Jamaica and Trinidad. METHODS:
      Population rates of HTLV-I infection were calculated from available census
      reports and serosurvey data. Incidence rates for NHL were calculated from all
      incident cases in Jamaica during 1984-1987 (n = 135) and from all incident cases
      in Trinidad during 1986-1990 (n = 117). Using biopsy material, we determined
      whether the immunophenotype of the tumor cells was T cell, B cell, or other. NHL
      incidence rates were computed according to HTLV-I status, age, sex, and tumor
      phenotype for each country separately and for both countries combined by
      weighting to the relative population size of each country. RESULTS: The age
      standardized NHL incidence rate (mean +/- SE) in Jamaica was 1.9 +/- 0.2 per
      100,000 person-years (PY). In Trinidad, the rate was 2.9 +/- 0.4 per 100,000 PY.
      Overall, the incidence of NHL increased with age and was higher in males than in
      females. In the HTLV-I-infected population, the incidence of NHL was inversely
      related to age, and age-specific rates were higher in males than in females. The
      NHL incidence in those estimated to have acquired HTLV-I infection in childhood,
      however, showed no sex difference, and one in 1300 such carriers (95% confidence
      interval: one in 1100 to one in 1600) per annum were estimated to be at such
      risk. For T-cell NHL, as proxy for adult T-cell lymphoma/leukemia, incidence was
      highest in those patients infected with HTLV-I early in life (perinatally or via
      breast milk), with high, sustained risk from early adulthood in both sexes.
      CONCLUSIONS: While overall NHL incidence rates reveal that HTLV-I endemicity does
      not impose an exaggerated lymphoma burden on these populations, the risk for
      lymphoma among carriers who acquire infection early in life is dramatic and is
      consistent with the hypothesis that virus exposure early in life is most
      important for lymphoma-genesis. IMPLICATIONS: Studies of HTLV-I carriers known to
      be infected in childhood may provide insight into markers intermediate in the
      lympho-magnetic process. Strategies to disrupt early-life transmission of HTLV-I,
      notably mother-infant transmission, may be critical in reducing the burden of
      lymphoreticular disease in these populations.

PMID- 7629871
TI  - Birthplace and classic Kaposi's sarcoma in Italy. Associazione Italiana Registri
      Tumori.

PMID- 7629872
TI  - Immunohistochemical detection of p53 in clinical breast cancers: a look at
      methodologic approaches.

PMID- 7629873
TI  - Re: Consumption of olive oil and specific food groups in relation to breast
      cancer risk in Greece.

PMID- 7629874
TI  - Re: Consumption of olive oil and specific food groups in relation to breast
      cancer risk in Greece.

PMID- 7629875
TI  - Detection of a point mutation in NQO1 (DT-diaphorase) in a patient with colon
      cancer.

PMID- 7629876
TI  - Bcl-2 overexpression and smoking history in head and neck cancer.

PMID- 7629877
TI  - Seasonal variation in melanoma progress.

PMID- 7629878
TI  - Viral-associated neoplasms in humans: additional clues.

PMID- 7629879
TI  - T-cell-mediated immunity to carcinoembryonic antigen in humans: an example of
      "swimming upstream"?

PMID- 7629880
TI  - Women flock to ABMT for breast cancer without final proof.

PMID- 7629882
TI  - Gene advisory group wrestles with its mission.

PMID- 7629881
TI  - Managed care takes control of prevention and control.

PMID- 7629883
TI  - Growth factor synthesis and human breast cancer progression.
AB  - Data obtained using long-established human breast cancer cell lines have
      suggested that autocrine growth factors secreted by the cells are important for
      their growth in vitro. Such data alone cannot definitively establish a role for
      autocrine growth factors in human breast cancer cell proliferation in vivo, but
      they create a paradigm that can be tested by analysis of data obtained with
      primary breast cancer cells and tissues. This review is aimed at examining
      experimental data obtained using fresh human breast cancer cells and tissues to
      determine whether the results obtained are consistent with predictions made by
      autocrine models of human breast cancer cell proliferation. Conceptually, for
      autocrine loops to be of primary importance in human breast cancer cell
      proliferation, breast cancer cells in vivo must 1) synthesize biologically active
      growth factors that are available to growth factor receptors, 2) synthesize the
      cognate growth factor receptors, 3) require the specific factors for
      proliferation, and 4) express the autocrine loop as a pathologic, rather than a
      physiologic, process. Since the proportion of tumors that express growth factors
      of a given family is consistently higher than the proportion of tumors that
      express the cognate receptors, it is likely that growth factor synthesis has an
      important, nonautocrine role in breast cancer progression as well. Data obtained
      with primary human breast cancer specimens indicate that growth factors
      synthesized by breast cancer cells have an important role in tumor development
      and progression but that these factors act in a true autocrine fashion only in a
      subset of tumors.

PMID- 7629884
TI  - Isolation and characterization of an immortal neoplastic cell line (KS Y-1) from
      AIDS-associated Kaposi's sarcoma.
AB  - BACKGROUND: Acquired immunodeficiency syndrome (AIDS) is associated with the
      occurrence of tumors such as Kaposi's sarcoma (KS) and B-cell lymphoma. However,
      no evidence exists yet that human immunodeficiency virus type 1, the causative
      agent of AIDS, is directly responsible for cell transformation. It is also not
      clear whether KS lesions, which are of complex cellularity, contain tumor cells
      derived from a true monoclonal malignancy (originating from a single malignant
      cell) or whether the lesions are just polyclonally hyperplastic in nature
      (containing increased numbers of normal cells). In fact, the presence of
      malignant KS cells has never been unequivocally shown in AIDS-associated KS, and
      previously isolated KS cell cultures were not immortal or malignant. PURPOSE: Our
      purpose was to (a) utilize technology that could facilitate isolation and
      enrichment of tumor cells from AIDS-associated KS lesions, (b) establish and
      characterize an immortalized KS cell line, and (c) test the malignant potential
      of such a cell line in animal models. METHODS: Mononuclear cells were isolated
      from 2.5 L of pleural effusion from an AIDS-associated KS patient. T-lymphocytes,
      B-lymphocytes, monocytes/macrophages, and fibroblasts were removed by a
      cytotoxicity method, using monoclonal antibodies specific for cell surface
      markers and baby rabbit complement. KS cells were cultured in the absence of
      exogenous growth factors in an effort to select for transformed cells capable of
      self-sustained growth. The karyotype abnormalities were detected by G-banded
      marker studies, and phenotypic markers were determined by indirect
      immunofluorescence and immunocytochemical methods. Beige nude XID and severe
      combined immunodeficient mice were used to evaluate the tumorigenic, angiogenic,
      and metastatic potentials of cells. RESULTS: An immortalized cell line, named KS
      Y-1, was isolated. Its phenotype is similar to that of endothelial cells with
      positive CD34 and CD31 markers. Tetraploid chromosomal abnormalities were found
      in primary fresh KS tissue and in vitro passages of KS Y-1 cells. These cells
      promoted tumorigenesis, angiogenesis, and metastasis in immunodeficient mice.
      Tumors produced at the site of injection as well as metastases in the lung,
      spleen, pancreas, gastrointestinal tract, and skin showed a human tetraploid
      karyotype. KS Y-1 cells show high plating efficiency. CONCLUSION: The KS Y-1 cell
      line could be the first evidence of AIDS-associated KS cells that may develop
      clones with an indisputable malignant cell phenotype. IMPLICATIONS: KS Y-1 cells
      in the in vivo mouse model can be used to study the effects of therapeutic
      compounds in advanced KS.

PMID- 7629885
TI  - Generation of human cytotoxic T cells specific for human carcinoembryonic antigen
      epitopes from patients immunized with recombinant vaccinia-CEA vaccine.
AB  - BACKGROUND: The human carcinoembryonic antigen (CEA), which is expressed in
      several cancer types, is a potential target for specific immunotherapy using
      recombinant vaccines. Previous studies have shown that when the CEA gene is
      placed into vaccinia virus, the recombinant vaccine (rV-CEA) can elicit T-cell
      responses in both rodents and non-human primates. PURPOSE: Our objective was to
      determine if rVCEA could elicit CEA-specific T-cell responses in humans with
      appropriate human leukocyte antigen (HLA) motifs. METHODS: Peripheral blood
      lymphocytes (PBLs) obtained from patients with metastatic carcinoma, both before
      and after vaccination with rV-CEA, were analyzed for T-cell response to specific
      9- to 11-mer CEA peptides selected to conform to human HLA class I-A2 motifs.
      RESULTS: While little or no T-cell growth was seen from preimmunization PBLs of
      patients pulsed with CEA peptides and interleukin 2 (IL-2), T-cell lines were
      obtained from PBLs of patients after vaccination with one to three cycles of
      stimulation. Cytolytic T-cell lines from three HLA-A2 patients were established
      with a 9-amino acid peptide (CAP-1), and the CD8+/CD4+ double-positive T-cell
      line (V24T) was chosen for detailed analysis. When autologous Epstein-Barr virus
      (EBV)-transformed B cells were either incubated with CAP-1 peptide or transduced
      with the CEA gene using a retroviral vector, they were lysed by the V24T cell
      line, but allogeneic non-A2 EBV-transformed B cells were not. The SW403 human
      colon carcinoma cell line, which is CEA positive and HLA-A2 positive, was also
      lysed by the V24T cell line, while two non-HLA-A2 CEA-positive colon carcinoma
      cell lines were not. To further confirm the class I HLA-A2 restricted nature of
      the V24T cytotoxicity, the non-HLA-A2 SW837 CEA-expressing colon carcinoma cell
      line was infected with a recombinant vaccinia virus expressing the HLA class I-A2
      gene, and it became susceptible to V24T lysis. Cells infected with vector alone
      were not lysed. CONCLUSIONS: This study demonstrates for the first time (a) the
      ability to generate a human cytolytic T-cell response to specific epitopes of
      CEA, (b) the class I HLA-A2 restricted nature of the T-cell mediated lysis, and
      (c) the ability of human tumor cells to endogenously process CEA to present a
      specific CEA peptide in the context of major histocompatibility complex for T
      cell-mediated lysis. IMPLICATIONS: These findings have implications in the
      development of specific second-generation cancer immunotherapy protocols.

PMID- 7629886
TI  - Risk of cancer in relatives of prostate cancer probands.
AB  - BACKGROUND: It is estimated that there will be more than 244,000 new prostate
      cancer cases diagnosed and that more than 40,000 men will die of this disease
      during 1995. Evidence exists for a hereditary predisposition to prostate cancer,
      but the proportion of cases attributable to the inheritance of a specific gene or
      genes is not large. Some hereditary cancer syndromes involve more than one tumor
      site, and some studies have reported a familial association between prostate
      cancer and other cancers. The presence of other cancers in prostate cancer
      families may indicate a specific type of hereditary predisposition. PURPOSE: We
      studied families that were selected because of the presence of prostate cancer to
      determine whether hereditary prostate cancer is associated with cancers at other
      sites and possibly with other heritable cancer syndromes. METHODS: Data from two
      distinct study populations were studied retrospectively. The first population
      consisted of 690 case patients undergoing radical prostatectomy who were not
      selected for family history of prostate cancer and 640 control subjects who were
      the spouses or female companions of the case patients. The second population
      consisted of 75 multiplex families (i.e., families with multiple cases of
      prostate cancer) referred because they fulfilled the criteria for hereditary
      prostate cancer. A comparison between case and control populations for the
      occurrence of 14 aggregated groups of cancer was performed. Data were analyzed
      using Poisson regression, and relative risks (RRs) and their 95% confidence
      intervals (CIs) were calculated. RESULTS: Brothers and fathers of prostate cancer
      probands have a statistically significant higher risk of prostate cancer than the
      male first-degree relatives of control subjects (RR = 1.76; 95% CI = 1.28-2.43).
      Therefore, the risk for prostate cancer is 76% higher among first-degree
      relatives of prostate cancer patients compared with first-degree relatives of
      control subjects. This higher risk was not modified by an occurrence of breast
      cancer in the pedigree. Also, a statistically significant higher risk was found
      for tumors of the central nervous system in hereditary families (RR = 3.02; 95%
      CI = 1.08-8.41). Statistically significant higher risks of cancer at other major
      sites, such as breast, ovary, or endometrium were not observed in these families.
      CONCLUSIONS: Even among families that were specifically selected because of the
      presence of prostate cancer, risks for cancer at other sites appeared not to be
      increased. Therefore, hereditary prostate cancer appears to be a relatively site
      specific disease, and it does not seem to be a part of other hereditary cancer
      syndromes.

PMID- 7629887
TI  - Heterogeneity of human neuroblastoma cell lines in their proliferative responses
      to basic FGF, NGF, and EGF: correlation with expression of growth factors and
      growth factor receptors.
AB  - Growth factors can induce both proliferation or differentiation of neuroblastoma
      (NB) cells through interaction with specific receptors. Using two automated
      colorimetric assays for determinations of cell numbers, the present study
      demonstrates that a) different NB and neuroepithelioma cell lines show distinct
      responses, both qualitatively and quantitatively, to basic FGF (bFGF), NGF, and
      EGF; b) even closely related NB cell lines (e.g., SK-N-SH, SH-SY5Y, and SHEP) do
      not respond uniformly to these factors; c) responses of the two neuroepithelioma
      cell lines employed (SK-N-MC and CHP-100) differ, but match those of certain NB
      cell lines; and d) two growth factors, bFGF and EGF, may both stimulate or
      inhibit proliferation, depending on the cell line studied. Specifically, IMR-32,
      SK-N-SH, and SH-SY5Y showed a mitogenic response to each growth factor. Maximal
      proliferative responses ranged from 204-355% as compared to controls (100%).
      GICAN was stimulated by NGF (199%), and SK-N-MC and NMB by EGF (282 and 140%,
      respectively), but other factors were ineffective. CHP-100 and GIMEN were
      inhibited by bFGF. NGF and EGF were not effective on CHP-100 cells, while EGF
      caused an arrest of mitogenic activity in GIMEN cells, and NGF stimulated their
      proliferation. Cell lines SHEP and LAN1 did not respond to any factor. To begin
      to analyze putative relationships of growth factor responsiveness and growth
      factor/growth factor receptor expressions, IMR-32, GIMEN, and LAN1 cell lines
      were studied for the presence of bFGF, NGF, FGF receptors (R)-1 (flg) and FGFR-4,
      trk, and low-affinity NGF receptor (p75) mRNAs.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7629888
TI  - Cyclic adenosine-3',5'-monophosphate potentiates the synaptic potential mediated
      by NMDA receptors in the amygdala.
AB  - An in vitro slice preparation of rat amygdala was used to study the actions of
      forskolin and cyclic adenosine-3',5'-monophosphate (cAMP) analogues on the N
      methyl-D-aspartate (NMDA) receptor-mediated synaptic potential (EPSPNMDA).
      Intracellular recordings were made from basolateral amygdala neurons in the
      presence of 6-cyano-7-nitroquinoxaline-2,3-di-one (CNQX, 10 microM) and
      picrotoxin (50 microM) to pharmacologically isolate the EPSPNMDA. Application of
      forskolin (25 microM) markedly and persistently potentiated the EPSPNMDA. In
      contrast, the inactive forskolin analogue, 1,9-dideoxy-forskolin, failed to
      affect the EPSPNMDA significantly. Superfusion of dibutyryl-cAMP (dbcAMP, 200
      microM) for 15 min caused a transient depression of the amplitude of EPSPNMDA.
      The EPSPNMDA amplitude was reduced to 68 +/- 3% of control (n = 10) 15 min after
      the application, restored to its control value within 25 min, and followed by a
      long-term potentiation (LTP). Pretreating the slices with 8-cyclopentyl-1,3
      dipropyl-xanthine (DPCPX, 5 microM), a selective A1 receptor antagonist, blocked
      the transient depressive phase produced by dbcAMP. This result suggests that the
      transient depression induced by dbcAMP was likely due to the interaction of
      dbcAMP or its breakdown products with adenosine A1 receptors. To determine the
      site of action, we examined the effect of forskolin on the postsynaptic responses
      to exogenously applied NMDA. Forskolin potentiated the postsynaptic
      depolarization induced by NMDA, suggesting that the enhancement is mediated, at
      least in part, by a persistent upregulation of postsynaptic NMDA receptor
      operated conductances. Occlusion experiments were performed to examine whether
      the sustained enhancements of EPSP(NMDA) produced by tetanic stimulation (TS) and
      forskolin share a common mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7629889
TI  - Macrophage inflammatory protein 1-alpha mRNA expression in an immortalized
      microglial cell line and cortical astrocyte cultures.
AB  - Macrophage inflammatory protein 1 (MIP-1) is a recently characterized
      inflammatory and chemokinetic cytokine. Proinflammatory stimuli have been shown
      to induce expression of MIP-1 by macrophages. We hypothesized that microglia and
      astrocytes express MIP-1 alpha because of their many immunologic similarities to
      macrophages. MIP-1 alpha mRNA was examined with quantitative reverse
      transcription and polymerase chain reaction in an immortalized mouse microglial
      cell line (BV-2) and in mouse cortical astrocyte cultures. We found that in both
      the BV-2 microglial cell line and in astrocyte cultures, MIP-1 alpha mRNA was
      strongly induced by lipopolysaccharide and the phorbol ester PMA. MIP-1 alpha
      mRNA was reduced by dBcAMP, interferon-gamma, and PGE1. Dexamethasone decreased
      MIP-1 alpha mRNA levels in astrocyte cultures, but not in BV-2 microglial cells.
      Interleukin-1 beta, tumor necrosis factor alpha, and MIP-1 alpha had no effect on
      MIP-1 alpha mRNA expression. These findings demonstrate that MIP-1 alpha mRNA is
      expressed by cultured glial cells and is regulated by proinflammatory and anti
      inflammatory stimuli. MIP-1 alpha may be expressed by microglia and astrocytes in
      vivo, and may help modulate cerebral inflammation.

PMID- 7629890
TI  - Death of septal cholinergic neurons produced by chronic exposure to glutamate is
      prevented by the noncompetitive NMDA receptor/channel antagonist, MK-801: role of
      nerve growth factor and nitric oxide.
AB  - To study the sequence of degenerative events possibly associated with cholinergic
      cell death in Alzheimer's disease, septal cholinergic neurons derived from rat
      embryonic brains were exposed to chronic excitotoxic stress by glutamate. Counts
      of choline acetyltransferase (ChAT)-immunopositive neurons and measurement of
      ChAT activity revealed that concentrations of glutamate on the order of 70 microM
      killed 50% of cholinergic neurons after 24 hr of treatment. Neurotoxic effects
      were not aimed at cholinergic neurons specifically, since other populations of
      cells present in these cultures were also affected at similar concentrations. The
      noncompetitive N-methyl-D-aspartate (NMDA) receptor channel antagonist MK-801 (10
      microM) abolished acute neuronal swelling and rescued from late degeneration both
      cholinergic and noncholinergic cells when concentrations of glutamate up to 500
      microM were added to the cultures. Protective effects declined progressively with
      increasing concentrations of the amino acid, even when MK-801 was raised to its
      highest nontoxic levels, e.g., 50 microM. the kainate/quisqualate receptor
      antagonist CNQX provided no protection alone or in combination with MK-801. Nerve
      growth factor (NGF), used in standard culture conditions to stimulate the
      expression of the cholinergic phenotype, was shown not to influence excitotoxic
      neurodegenerative changes. Several observations suggested that nitric oxide (NO)
      may act as an intercellular messenger of NMDA-mediated cell death in septal
      cultures: 1) Most of the cholinergic neurons contained the NO synthase enzyme as
      characterized by NADPH-diaphorase (NADPH-d) staining; 2) sodium nitroprusside
      (SNP) [a chemical with the ability of generating NO] was capable of mimicking
      some of the aspects of the glutamate-induced degenerative process; 3) the rise in
      cyclic GMP which was observed in the presence of toxic levels of glutamate and
      which is usually taken as an index of NO production, was antagonized by MK-801
      and by the inhibitor of the NO synthase enzyme, L-NOARG. Yet, the fact that L
      NOARG and its congener, L-NAME, were ineffective in preventing glutamate-induced
      neurodegenerative changes in our culture system did not substantiate our working
      hypothesis. Altogether these results suggest that glutamate-induced cholinergic
      neuronal death is the consequence of an overstimulation of NMDA receptors and
      that neither NGF nor NO plays a key role in the degenerative process.

PMID- 7629891
TI  - Regeneration of specific nerve cells in lesioned visual cortex of the human
      brain: an indirect evidence after constant stimulation with different spots of
      light.
AB  - The defective parts of the visual field of two brain-injured patients were
      stimulated with different spots of light. There is evidence for at least five
      independent visual functions which can be restored due to constant stimulation of
      the blind part of the visual field: (1) The constant stimulation of the blind
      part of the visual field with spots of white light leads to an increase of the
      visual field for the perception of white light only. (2) The constant stimulation
      with spots of light of different wavelengths leads to an increase of the visual
      field for different color perception. To enlarge the visual field for the
      perception of the color red, a light stimulus with the wavelength of 656
      nanometers (nm) was used; for the visual field for the perception of the color
      green 525 nm; for yellow 578 nm; and for blue 450 nm. (3) The constant
      stimulation of the blind visual field with black and white light bars of
      different orientations and constellations leads to an increase of the foveal
      acuity and an improvement of form perception in the periphery of the visual
      field. The results suggest that the recovery of visual functions, different color
      perception and form perception, may depend upon neuronal regeneration in the
      human visual cortex; regeneration occurs with adequate and constant stimulation
      of its specific neurons.

PMID- 7629892
TI  - Purification and characterization of a low molecular weight endogenous glutamate
      binding inhibitor (LGBI) in porcine brain.
AB  - One of the endogenous substances which modulate glutamate receptor binding was
      isolated and highly purified from porcine brain. The purification involved
      extraction of brain tissue with doubled distilled water, followed by gel
      filtration, anion exchange, cation exchange, and several steps of C18 reverse
      phase high performance liquid chromatography (HPLC). A low molecular weight
      glutamate binding inhibitor (LGBI) was purified to apparent homogeneity as judged
      from the elution profile of an HPLC column, in which a symmetrical peak was
      obtained when the eluate was monitored at 220 nm. The LGBI appears to be a small
      molecule (< 2 kD) that is heat- and acid/base-stable. The highly purified LGBI
      has no effect on GABAA and benzodiazepine receptor binding. The LGBI is not L
      glutamate, L-aspartate or other negatively charged endogenous substances, since
      they are clearly separated from the LGBI in anion exchange chromatography. The
      inhibitory effect of the LGBI on [3H]L-glutamate binding is reversible, and it
      only changes the Bmax while the Kd remains the same. Since the membrane
      preparations used for [3H]L-glutamate binding assays for the detection of LGBI
      activity were enriched with quisqualate (QA)-sensitive subtypes, it was suggested
      that the LGBI could be a modulator of the QA receptor. Some amino acids which
      produce significant inhibition of glutamate binding activity were also compared
      with the LGBI, and they all showed no resemblance to the LGBI. The chemical
      structure of the LGBI remains to be determined.

PMID- 7629894
TI  - Brain-specific expression of human microtubule-associated protein 1A (MAP1A) gene
      and its assignment to human chromosome 15.
AB  - We isolated several cDNA fragments by immunoscreening a human cDNA library with
      our monoclonal antibody, BG5, that showed neuronal staining on human and rat
      brain sections. A 1,570 bp sequence of one cDNA fragment showed 75% homology to
      the rat microtubule-associated protein 1A (MAP1A) cDNA sequence. This rat MAP1A
      like human cDNA was highly specific to the adult brain among human tissues
      tested, and was expressed in various brain regions including white matter. The
      size of the mRNA detected with Northern blot analysis in adult human brain
      equaled 10 kb. The gene of this cDNA was assigned to human chromosome 15 that has
      a syntenic region of mouse chromosome 2, where the mouse MAP1A gene has been
      assigned. These results indicate that this rat MAP1A-like cDNA is a portion of
      human MAP1A and is a conserved molecular species among humans and rodents.

PMID- 7629893
TI  - Cloning of rat grp75, an hsp70-family member, and its expression in normal and
      ischemic brain.
AB  - Following metabolic stress a variety of gene products are induced in cells in the
      brain, some of which may protect the tissue from subsequent stresses. The heat
      shock proteins (hsps), in particular hsp70, have been widely studied in this
      context, but evidence for the involvement of known hsps in protection of the CNS
      is inconclusive. We have therefore undertaken the search for other stress-induced
      proteins which may mitigate ischemic injury. Beginning with degenerate RT-PCR, we
      have isolated a rat-brain cDNA encoding a protein highly similar to human grp75,
      a mitochondrial member of the hsp70-family of stress proteins. It is also highly
      similar to two non-mitochondrial proteins; mortalin, a senescence-related gene
      product, and pbp74, a protein implicated in B-cell peptide processing. Sequence
      structure and phylogenetic analyses predict mitochondrial localization and
      induction by a calcium ionophore and glucose deprivation in PC12 cells support
      its identification as rat grp75. In situ analysis of normal brain reveals an
      unusual distribution, with very high expression in neurons of the basal
      forebrain, reticular and subthalamic nuclei, globus pallidus, amygdala and
      elsewhere. grp75-mRNA is upregulated following focal brain ischemia in a
      distinctive fashion. When the degree of injury is small, induction occurs in the
      area of injury, similar to the pattern observed for hsp70. However, when the
      injury is extensive, hsr is upregulated in neurons outside the ischemic area. The
      induction of grp75 may represent a sensitive marker of metabolically compromised
      tissue.

PMID- 7629895
TI  - Site-directed mutagenesis of human CNTF: functional analysis of recombinant
      variants.
AB  - Ciliary neurotrophic factor (CNTF), interleukin-6 (IL-6), leukemia inhibitory
      factor (LIF), and oncostatin M (OSM) share functional properties, a predicted
      common helical framework, and partially identical receptor components. CNTF is a
      survival promoting factor for various types of neurons in vitro and in vivo. In
      the present study, structural features essential for the biological function of
      human CNTF were investigated. Several recombinant CNTF variants were constructed
      by PCR and expressed in E. coli. Their survival promoting activities were
      determined using cultures of embryonic chick and newborn rat dorsal root ganglion
      cells. Deletion of 14 N-terminal and 18 C-terminal amino acids significantly
      increased bioactivity compared to wild-type (wt) CNTF. Further truncation of the
      CNTF molecule at the N- or C-terminus resulted in a significant reduction or
      complete loss of activity. Substitution of two amino acids (Lys154Glu and
      Trp157Pro) abolished the survival promoting effect. Recently described analogous
      substitutions in IL-6 had resulted in a partial IL-6 receptor antagonist.
      However, the double substitution variant had no significant inhibitory effect on
      wtCNTF activity in assays with both wt and mutant factor. The CNTF variants
      constructed had almost identical effects on both chick and rat neurons indicating
      a close similarity of the avian and the mammalian CNTF receptor complex. The
      present results also demonstrate that a core segment of the CNTF molecule is
      indispensable for biological function. Analogous segments important for activity
      have already been identified in the related molecules IL-6, LIF, and OSM. Thus,
      our data confirm the close structural relationship of CNTF to these
      "neuropoietic" cytokines. In addition, they demonstrate that site-directed
      mutagenesis of recombinant human CNTF can yield molecules which show increased
      survival promoting activity on mammalian neurons.

PMID- 7629896
TI  - Disturbances of potassium homeostasis in poisoning.
AB  - Unless renal function is impaired or rhabdomyolysis is severe, hyperkalemia is a
      relatively uncommon metabolic complication of poisoning. In contrast, marked
      hypokalemia is a more common problem and may have serious sequelae. Most
      potassium disturbances in acute poisoning are due to disruption of extra-renal
      control mechanisms, notably the activity of Na+/K+ ATPase and K+ channels.
      Hypokalemia occurs because of increased Na+/K+ ATPase activity (e.g. beta 2
      agonist, theophylline or insulin poisoning), competitive blockade of K+ channels
      (e.g. barium or chloroquine poisoning), gastrointestinal losses and/or alkalosis.
      Hyperkalemia follows inhibition of Na+/K+ ATPase activity (e.g. by digoxin),
      increased uptake of potassium salts, disruption of intermediary metabolism (e.g.
      cyanide poisoning), activation of K+ channels (e.g. fluoride poisoning), and the
      presence of acidosis and rhabdomyolysis, particularly if the latter is
      complicated by renal failure. Hypokalemia results in generalized muscle weakness,
      paralytic ileus, ECG changes (flat or inverted T waves, prominent U waves, ST
      segment depression) and cardiac arrhythmias (atrial tachycardia +/- block, AV
      dissociation, VT, VF). Hyperkalemia is associated with abdominal pain, diarrhea,
      muscle pain and weakness, ECG changes (tall peaked T waves, ST segment
      depression, prolonged PR interval, QRS prolongation) and cardiac arrhythmias (VT,
      VF). Significant disturbances of potassium homeostasis are often unrecognized and
      may cause considerable morbidity and mortality. Prompt recognition and
      appropriate treatment of these disturbances could be life-saving.

PMID- 7629897
TI  - Severity and carbamazepine level at time of initial poison center contact
      correlate with outcome in carbamazepine poisoning.
AB  - We reviewed data from carbamazepine poisonings reported to the Kentucky Regional
      Poison Center from January 1986 through March 1992 to identify information
      available at the time of poison center contact which correlates to outcome. The
      Spearman rank correlation test was used to describe the relationship between two
      ordinal variables and interval-level variables. The Kruskal-Wallis test was used
      to determine the relationship between categorical and ordinal variables. Two way
      analysis of variance was used to test the effect of routine carbamazepine use on
      final severity and carbamazepine level of 345 reports involving carbamazepine
      poisoning; 263 (76%) involved only carbamazepine ingestion and formed the
      database. One hundred eighty four (70%) carbamazepine ingestions occurred in
      victims < or = 17 years old, 79 (30%) occurred in adults. Severity assigned at
      the time of initial poison center contact was significantly correlated with
      outcome severity for children and adults (r > or = 0.9, p < 0.00001). The amount
      reported ingested influenced the correlation between initial and final severity;
      whereas, time elapsed between ingestion and poison center contact did not alter
      the correlation between initial and final severity. The reason for ingestion was
      significantly correlated with outcome (p < 0.00001). A significant correlation
      between outcome and peak carbamazepine level for each age group was observed
      (pediatric r = 0.5, p < 0.00001, and adult r = 0.4, p = 0.008). Carbamazepine
      levels > 85 mumol/L (> 20 mcg/mL) were associated with more severe toxicity.

PMID- 7629898
TI  - The effect of oral deferoxamine on iron absorption in humans.
AB  - Acute iron overdose is a serious cause of morbidity and mortality, however,
      optimal gastric decontamination procedures in iron overdose are unclear. In order
      to determine the effectiveness of oral deferoxamine mesylate solution in humans
      to prevent the absorption of iron in acute exposures, the following prospective
      case control crossover study was designed. Seven informed adult human volunteers
      were given an oral dose of 5 mg/kg elemental iron alone in a control phase and
      again in an experimental phase followed by a single equimolar dose of oral
      buffered deferoxamine solution. Plasma iron concentrations were determined
      spectrophotometrically for eight hours following administration of iron alone and
      following doses of iron with deferoxamine. There was no significant difference in
      peak iron concentration, time to peak iron concentration or area-under-the-curve
      between the two groups. Based on our results, equimolar doses of oral
      deferoxamine do not appear to decrease the absorption of low doses of oral iron
      in humans.

PMID- 7629899
TI  - Detection of occupational lead nephropathy using early renal markers.
AB  - Automotive use of leaded gasoline continues to be an important source of
      occupational exposure to lead in India and other countries. The present study
      assessed the renal function and markers of early renal damage of 22 mechanics at
      three automobile garages. Urinary N-acetyl-3-D-glucosaminidase activity and beta
      2-microglobulin levels were significantly increased in auto garage mechanics with
      blood leads of 30-69 micrograms/dL. A significant correlation was observed
      between blood lead levels and urinary N-acetyl-3-D-glucosaminidase activity but
      not with urine beta-2-microglobulin levels. A marginal impairment in creatinine
      clearance was not statistically significant. Urinary N-acetyl-3-D-glucosaminidase
      activity offers a sensitive monitor of blood lead and renal tubular injury.

PMID- 7629900
TI  - Combined use of glucagon and milrinone may not be preferable for severe
      propranolol poisoning in the canine model.
AB  - In a previous study of propranolol poisoning, glucagon and milrinone
      significantly increased cardiac output, but the improvement caused by glucagon
      was almost entirely due to the chronotropic effect. This study investigates the
      combined effect of glucagon, in a dose not inducing tachycardia, and milrinone on
      beta-blocker poisoning. Following the administration of 10 mg/kg propranolol IV
      over ten minutes, dogs (N = 20) were divided into four treatment groups, group S
      (saline), group G (glucagon 2.5 micrograms/kg), group M (milrinone 100
      micrograms/kg), and group G + M (glucagon 2.5 micrograms/kg plus milrinone 100
      micrograms/kg). Hemodynamic parameters were observed over the next thirty
      minutes. Heart rate, cardiac output, and mean arterial pressure were decreased in
      all groups after the administration of propranolol. Heart rate, mean arterial
      pressure, cardiac output, and stroke volume recovered to the baseline values in
      group G + M. However, heart rate in group G + M showed a significant increase
      versus the other three groups. In a canine model of severe propranolol poisoning,
      the combined effect of glucagon 2.5 micrograms/kg and milrinone 100 micrograms/kg
      brought about a significant hemodynamic improvement, but it was accompanied by an
      excessive increase of heart rate. Combined therapy of milrinone and glucagon may
      not be preferable therapy in beta-blocker poisoning in the canine model.

PMID- 7629901
TI  - Experimental studies on the toxicity of lithographic developer solution.
AB  - The purpose of this study was to determine whether the toxicity of a lithographic
      developer solution which contains hydroquinone is caused by hydroquinone or the
      alkaline lithographic developer solution. Male Wistar rats were divided into
      seven groups. In four groups, rats were dosed orally with 3% hydroquinone or 3%
      hydroquinone in 3% lithographic developer solution. Hydroquinone levels were
      measured after one and 24 hours. In two groups, rats were dosed orally with 6%
      hydroquinone or 6% hydroquinone in lithographic developer solution. In the
      seventh group, rats received the alkaline solution only. Hydroquinone measurement
      was made using gas chromatography-mass spectrometry. Hydroquinone was rapidly
      absorbed from the gastrointestinal tract and subsequently distributed throughout
      the body. Nearly all hydroquinone was excreted in the urine as either a
      glucuronide or a sulfate (78-82%) within 24 hours. All rats administered 6%
      hydroquinone in non-alkaline vehicle died, but the mortality rate of rats
      administered 6% hydroquinone in lithographic developer solution was 60%. Tissue
      hydroquinone was lower at one hour and 24 hours after administration in
      lithographic developer solution than in equal dose of hydroquinone in non
      alkaline vehicle suggesting decreased absorption in an alkaline pH. Hydroquinone
      was not associated with gross pathologic changes of the intestine but all animals
      treated with lithographic developer solution or alkaline solution had congestion,
      hemorrhagic petechiae and purple-brown discoloration throughout the small
      intestine. The combination of alkaline/formaldehyde diluent with hydroquinone may
      delay hydroquinone absorption but increase the risk of intestinal necrosis.

PMID- 7629902
TI  - Explosion risk from swimming pool chlorinators and review of chlorine toxicity.
AB  - Two patients were admitted to the hospital emergency room in respiratory distress
      after an accidental explosion involving chlorinating agents for the swimming
      pool. The two primary agents involved were calcium hypochlorite and trichloro-s
      triazinetrione; both are commonly used chlorinating agents. These chemicals were
      tested in a bomb apparatus measuring temperature and gas production. Combining
      the two chlorinators at 2, 6, 12, or 18 g of each produced a progressive increase
      in gas production from 234 to 1422 mL. The temperature increased from 30 degrees
      C at 2 g to 63 degrees C at 18 g. The time to complete the reaction decreased
      from 6.2 minutes at 2 g to 3.8 minutes at 18 g. The third run at the 18 g level
      resulted in an explosion. The results indicate that gas generation is dependent
      on both products. The addition of organic material was abandoned because of the
      explosive nature of the reaction. The amount of calcium hypochlorite primarily
      determines the rate of reaction and heat generation. Appropriate emergency action
      and treatment for chlorine gas is discussed.

PMID- 7629903
TI  - Chlorine/chloramine.

PMID- 7629904
TI  - A case report of venlafaxine toxicity.
AB  - Venlafaxine hydrochloride is a novel bicyclic antidepressant which inhibits the
      reuptake of serotonin, norepinephrine and, to a lesser extent, dopamine. A 41
      year-old female ingested 4.5 g venlafaxine, 500 mg diphenhydramine, 50 mg
      thiothixene and subsequently experienced severe central nervous system depression
      requiring intubation. She also developed elevated systolic and diastolic blood
      pressures and sinus tachycardia. The patient was decontaminated with gastric
      lavage and activated charcoal. She regained consciousness within a few hours and
      was extubated nine hours after ingestion. This case demonstrates that severe
      central nervous system depression may follow venlafaxine overdose.

PMID- 7629905
TI  - Moldy sugarcane poisoning--a case report with a brief review.
AB  - A five-year-old girl developed an acute encephalopathy after eating a piece of
      moldy sugarcane. Delayed symptomatic dystonia was the main effect; cranial CT
      scans revealed bilateral lenticular lucencies. This case is typical of moldy
      sugarcane poisoning cases previously reported only in China. 3-Nitropropionic
      acid produced by Arthrinium sp is the most likely etiologic agent.

PMID- 7629906
TI  - The hazards of chloroquine self prescription in west Africa.
AB  - We report a severe accidental chloroquine poisoning in a West African adult. This
      intoxication results from the widespread practice in Senegal of taking mild doses
      of chloroquine for a few days (i.e. 300 mg x 3 for 3 or 5 days) following the
      onset of any fever suspected of being a malaria attack. To our knowledge, this
      practice and this kind of poisoning have not been reported before. The present
      clinical case demonstrated that self-medication can be the cause of severe
      chloroquine poisoning responsible for arrhythmia (torsades de pointes). In this
      clinical case, no diazepam was administered. However, there were no further
      problems and the patient was discharged three days after admission to the
      intensive care unit.

PMID- 7629907
TI  - Chronic lead intoxication at an indoor firing range in Taiwan.

PMID- 7629908
TI  - Toxic polyneuropathy due to flour contaminated with tricresyl phosphate in China.

PMID- 7629909
TI  - Acute tubular necrosis following endosulfan insecticide poisoning.

PMID- 7629910
TI  - Ticlopidine-induced prolonged cholestasis.

PMID- 7629911
TI  - Clinical effects of the fruit juice of Ecbalium elaterium in the treatment of
      sinusitis.

PMID- 7629912
TI  - A simple means of calculating blood lead concentrations.

PMID- 7629913
TI  - Calculating blood lead concentrations: a perspective.

PMID- 7629914
TI  - Surgical treatment of pericardial effusion in cancer patients.
AB  - 31 cancer patients with symptomatic pericardial effusion were treated by
      subxiphoid pericardiotomy with simultaneous pleuropericardial window creation.
      There were no patients who died during surgery. In all patients, relief of
      cardiac compression by the effusion was immediate and complete. 10 patients died
      of advanced malignancy within 30 days after operation without evidence of
      recurrent pericardial effusion. During the period of follow-up, another seventeen
      patients died, and no death was related to pericardial effusion. It is concluded
      that pleuropericardial window through the subxiphoid approach is the treatment of
      choice for pericardial effusion in cancer patients. The procedure provides
      immediate and long-lasting relief of cardiac compression with acceptable
      mortality and morbidity.

PMID- 7629915
TI  - Primary culture of mouse myoblasts.
AB  - The literature has revealed variations in the protocols for myoblast cultures,
      and little information is available on myoblast and fibroblast proliferation.
      Therefore, the purposes of this study were to establish a prudent protocol for
      myoblast cultures by comparing a variety of culturing procedures used in previous
      research and to quantitate myoblast proliferation and fusion under different
      culture conditions. In addition, the growth status of myoblasts and fibroblasts
      was investigated. Results indicate that the requirements for an ideal myoblast
      culture should include a combined enzyme of 0.25% trypsin and 0.2% collagenase
      type IV (1:1), a preplating time of approximately 15-20 minutes, and a seeding
      density at 1 x 10(5) cells/ml. Furthermore, the mouse sample should be those of
      newborns. A better proliferative capacity of myoblasts was noted in an incubator
      of 10% CO2, coupled with Dulbecco's MEM plus 15% fetal calf serum. The doubling
      times of myoblasts were shorter than those of fibroblasts, and myoblast number
      reached its highest at 4 and 5 days. The findings of this study are valuable in
      understanding the growth status of myoblasts and fibroblasts in primary cultures.
      Moreover, the establishment of requirements for a good growth of myoblast
      cultures will facilitate myoblast transfer therapy.

PMID- 7629916
TI  - Body mass index and hyperuricemia differences between aboriginal and non
      aboriginal children in Taiwan.
AB  - To explore the relationship between the body mass index (BMI) and uric acid in
      different races before growing up into adulthood, we selected a total of 1236
      five to 14 year-old children in the period from March to December 1994. The
      children originated from three Aboriginal tribes (the Bunun, and the Paiwan
      tribes--classified as South-Aborigines and Atayal tribe as North-Aborigines) and
      two non-Aboriginal tribes (Fukein-Taiwanese and Hakka), all of whom are from the
      following four countries: Chien-Shih, Sandimen, Gaushuh and Sanmin. The results
      showed that the percentage of hyperuricemia (> or = 7.5 mg/dl) was 28.5%
      (352/1236) and of obesity (BMI > or = 22 kg/m2) was 9.5% (118/1236). Increased
      uric acid concentration was found to be related to age, sex, BMI, race,
      triglyceride (TG) and cholesterol levels in both the primary analysis and after
      the adjusted logistic regression model. Obesity did not vary with sex (OR = 1.0;
      95% CI = 0.7-1.5), or with Aborigines in north Taiwan as compared with non
      Aborigines (OR = 1.0, 95% CI = 0.6-1.6), but the logistic regression model
      adjusted for age indicated large BMI values for children with high serum uric
      acid concentration, triglyceride levels and the Aborigines who originated from
      south Taiwan. It was concluded from this study that both of the North-Aborigines
      and South-Aborigines made an important influence on serum uric acid concentration
      in children, especially the South-Aborigines made difference to BMI as compared
      with non-Aborigines and North-Aborigines.

PMID- 7629917
TI  - [The re-evaluation of the prevalence of trachoma in primary school children in
      Kaohsiung City].
AB  - For years, trachoma screening has been a routine part of the health examination
      program for all primary school children. In order to ascertain the current
      prevalence of trachoma in primary school children, we used clinical examination,
      immunofluorescein-monoclonal antibody and McCoy cell culture technique to examine
      771 children from 5 primary schools in Kaohsiung City. Using the results of the
      McCoy cell culture as a judgement standard, we found that 118 children (15.3%)
      had chlamydia trachomatis infections. The infection rates of children were
      statistically insignificant for sex, grade and location of school of children.
      Among the 118 infected children, most had none or mild (96.6%) conjunctival
      inflammation. Only 3 children (0.4%) had conjunctival cicatrization
      complications. These results showed that the repeated reinfections among these
      children were quite few. The McCoy cell culture was used to test the result of
      clinical diagnosis made by the senior ophthalmologists. The sensitivity of the
      clinical diagnosis was 50% and the predictive positive rate was 26.6%. It
      revealed that the diagnosis of trachoma made by clinical observation only was
      unreliable. The results of immunofluorescein-monoclonal antibody test showed that
      120 children (15.6%) had trachomatous infections. Its sensitivity was 68.4%, and
      specificity was 91.7%. It revealed that more care should be taken in quality
      control of laboratory techniques. From these results, we conclude: 1) the
      trachomatous infections of primary school children in Kaohsiung City are not
      serious; the repeated infections among

PMID- 7629918
TI  - [Locomotion of dystrophin-deficient mice].
AB  - The purpose of our study was to make a comparison of the motor function between
      murine dystrophy mice (MDX mice) and C57BL/10ScSn control mice. The locomotor
      activities of mice were measured by an animal three-dimension optical monitor.
      Measurements were performed at ages of 21, 45 and 60 days. Animals were tested in
      a dark and peaceful environment under room temperature (25 degrees C-27 degrees
      C) at night for an hour. Results showed that the most important differences were
      in data on vertical activities. Among 15 variables of locomotor activity detected
      by the optical activity monitor, the MDX mice and control mice at age 21 days
      showed significant differences in 12 variables. However, the MDX mice and control
      mice at age 45 days revealed significant differences in only 7 variables. The MDX
      mice and control mice at age 60 days had significant differences for only one
      variable. The results may be explained by the fact that dystrophin-deficient mice
      undergo more severe dystrophic degeneration at an early age (5 weeks) and new
      regeneration of their muscle fibres is prevalent. Moreover, a functional recovery
      occurred in MDX skeletal muscle which was probably due to the regeneration of
      dystrophic muscle.

PMID- 7629919
TI  - [The application of Moire topography in analysis of face among Taiwanese adults].
AB  - Moire topography has been used in human body measurement for many years. However,
      the technique has rarely been applied in human facial measurement. The purpose of
      this study was to review the basic principles and techniques of Moire topography,
      and to apply this technique in the three-dimension measurement of human faces.
      One hundred and thirty seven Taiwanese young adults aged from 18-22, including 70
      males and 67 females, took part. Angle Class I occlusal relationship without
      anterior crowding was selected in this study. The data collected from Moire
      topography were scanned and analyzed with the use of a computer. Eight x-values
      and 28 y-values were recorded, based on pre-set landmarks. The t-test was used to
      compare the male and female groups. The results of this study were also used to
      compare with the results reported in related studies. The conclusion are as
      follows: 1. Most of the data between male and female groups showed significant
      difference with the exception of the values of Y9, Y28 and Y29. The value of the
      female group was larger than that of the male group on Y23. However, compared
      with the male group, the females appeared to have smaller faces. 2. Compared with
      Kamura's data, this study showed that the Taiwanese young female group (TF) was
      larger than the Japanese young female group (JF) for the values of X2 X7 and X8.
      Most of the data for JF were larger than for TF in Y values. This proved that the
      Japanese young females had larger faces with smaller eyes. 3. The data between TF
      and the young female group of Taiwan aborigines (AF) showed significant
      difference at the values of X1, X2, X5 and X6, in which the AF was larger than
      TF. Contrarily, the TF values for X2, X4 and X8 were larger than those for the
      AF. It showed that the AF was larger in the facial width, the width between eyes,
      the nasal width, and the mouth width, but was smaller in the width of eyes.
      Furthermore, the AF was also larger than the TF in the values of Y2, Y11, Y12,
      Y13, Y14, Y15, Y16, Y17, Y18, Y23, Y24 and Y25. This showed that the AF had a
      long middle and lower face and high frontal protrusion. 4. The differences among
      TF, AF and JF: The narrowest facial breadth: TF The widest breadth of eyes: TF
      The widest breadth of nose: AF The widest breadth of mouth: AF The longest length
      of middle & inferior face: JF The highest height of frontal protrusion: AF The
      shortest length of nose: TF

PMID- 7629920
TI  - [Longitudinal study of postpartum women knowledge needs--parity and time series
      perspectives].
AB  - The purpose of this study was to explore the knowledge needs of postpartum women.
      A postpartum knowledge needs questionnaire was administered to 70 postpartum
      women during the 1st and 4th week postpartum. Data were analyzed by factor
      analysis to determine the relationships within categories of knowledge needs.
      Data were also analyzed by 2-factor repeated measure analysis of variance
      (ANOVA). The two factors included parity and time (period of measurement). The
      results indicated that the knowledge needs of postpartum women can be categorized
      as follows: (1) Knowledge of caring for the baby, (2) Knowledge of caring for
      one's self and (3) Knowledge of caring for other family members. The women during
      the 1st week postpartum reported a significantly higher need in knowledge of
      infant care than women during the 4th week postpartum. Multiparas showed a
      significantly higher need in knowledge of caring for other family members than
      primiparas.

PMID- 7629921
TI  - Using a titanium mesh plate to reconstruct the orbital floor after an
      incompletely reduced zygomaticomaxillary complex fracture.
AB  - A 30 year-old male came to us for correcting his severe left enophthalmos five
      months after a facial trauma in a traffic accident. CT scan of his left orbit
      showed a greatly increased orbital volume, which was resulted from the incomplete
      reduction of left zygomaticomaxillary complex (ZMC) fracture, unrepaired medial
      and lateral walls, and improper restoration of the orbital floor with a silicone
      sheet. Also, the decreased ocular volume, due to the evisceration of the ruptured
      eyeball with intraocular silicone ball implantation, contributed to the patient's
      enophthalmos. Because the patient refused any kind of osteotomy for his
      incompletely reduced and malunion ZMC fracture in the procedures of orbital
      reconstruction, correction of his severe enophthalmos became very difficult if
      not impossible. Therefore, we used a piece of titanium mesh plate about 2.5 x 4
      cm in size, and folded it into an L shape. The shorter part of the L-shaped plate
      was used to fix the whole plate by screwing it into the anterior surface of the
      inferior orbital rim. The longer part of the plate was used as a new orbital
      floor. To hold and push the intraocular implant upward and anteriorly, the longer
      part of the plate was adjusted to a level higher than the original floor level,
      and was bent upward gently in the posterior part. Postoperatively, the severe
      enophthalmos was markedly improved, and the patient was satisfied although an
      evident supratarsal sulcus was still present. After a follow-up of 18 months, no
      complication of migration, infection, or extrusion of the titanium mesh plate
      occurred.

PMID- 7629922
TI  - Technetium-99m albumin scintigraphy in the diagnosis of protein-losing
      enteropathy: a case report.
AB  - A 34-year-old female presenting with bilateral lower leg edema and distended
      abdomen was admitted to our hospital. The serum albumin was 1.42g/dl. Renal
      function and hepatic function were normal. Urinalysis did not show proteinuria.
      Tc-99m albumin scintigraphy was arranged for this patient to rule out protein
      losing enteropathy. The results demonstrated loss of albumin into the intestines.
      We conclude that Tc-99m albumin scintigraphy of the abdomen is a valuable adjunct
      in the diagnosis of protein-losing enteropathy.

PMID- 7629923
TI  - Intravenous disposition kinetics, oral and intramuscular bioavailability and
      urinary excretion of norfloxacin nicotinate in donkeys.
AB  - An aqueous solution of norfloxacin nicotinate (NFN) was administered to donkeys
      (Aquus asinus) intravenously (once at 10 mg/kg), intramuscularly and orally (both
      routes once at 10 and 20 mg/kg, and for 5 days at 20 mg/kg/day). Blood samples
      were collected at predetermined times after each treatment and urine was sampled
      after intravenous drug administration. Serum NFN concentrations were determined
      by microbiological assay. Intravenous injection of NFN over 45-60 s resulted in
      seizures, profuse sweating and tachycardia. The intravenous half-life (t1/2 beta)
      was 209 +/- 36 min, the apparent volume of distribution (Vd(area)) was 3.34 +/-
      0.58 L/kg, the total body clearance (ClB) was 1.092 +/- 0.123 x 10(-2) mL/min/kg
      and the renal clearance (C1R) was 0.411 +/- 0.057 x 10(-2) mL/min/kg. Oral
      bioavailability was rather poor (9.6% and 6.4% for the 10 and 20 mg/kg doses
      respectively). Multiple oral treatments did not result in any clinical
      gastrointestinal disturbances. After intramuscular administration (20 mg/kg),
      serum NFN concentrations > 0.25 microgram/mL (necessary to inhibit the majority
      of gram-negative bacteria isolated from horses) were maintained for 12 h. The
      intramuscular bioavailability was 31.5% and 18.8% for the 10 and 20 mg/kg doses
      respectively. After multiple dosing some local swelling was observed at the
      injection site. About 40% of the intravenous dose was recovered in the urine as
      parent drug. The results of comprehensive haematological and blood biochemistry
      tests indicated no abnormal findings except elevation in serum CPK (creatine
      phosphokinase) values after multiple intramuscular dosing.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7629924
TI  - Pharmacokinetics of ketoprofen after multiple intravenous doses to mares.
AB  - The pharmacokinetics and urinary excretion of ketoprofen in six healthy mares
      after the first and last of five daily intravenous doses of 2.2 mg of ketoprofen
      per kg body weight were investigated using a high-performance liquid
      chromatographic (HPLC) method for determining plasma and urinary ketoprofen
      concentrations. Plasma ketoprofen concentrations declined triexponentially after
      each dose with no significant differences in plasma concentrations or
      pharmacokinetic parameter values between the first and last doses. The harmonic
      mean of the terminal elimination half-life of ketoprofen after the first and last
      dose was 98.2 and 78.0 min, respectively. The median values of the total plasma
      clearance and the renal clearance after the first dose were 4.81 and 1.93
      mL/min/kg, respectively. Total plasma clearance was attributed to renal excretion
      of ketoprofen and metabolism of ketoprofen to a base-labile conjugate which was
      also excreted in the urine. Renal clearance of ketoprofen was attributed to renal
      tubular secretion since renal clearance was greater than filtration clearance.
      Urinary recovery of ketoprofen during the first 420 min after the first dose
      accounted for 26.4% of the dose as unconjugated ketoprofen and 29.8% of the dose
      as a base-labile conjugate of ketoprofen. Total urinary recovery of ketoprofen as
      unchanged ketoprofen and from base-labile conjugate represented 56.2% of the
      dose. Plasma protein binding of ketoprofen was extensive; the mean plasma protein
      binding of ketoprofen was 92.8% (SD 3.0%) at 500 ng/mL and 91.6% (SD 0.60%) at
      10.0 micrograms/mL.

PMID- 7629925
TI  - The influence of cimetidine on the pharmacokinetics of the enantiomers of
      verapamil in the dog during multiple oral dosing.
AB  - The disposition of intravenously (0.5 mg/kg) and orally (5 mg/kg) administered
      verapamil was studied in six dogs after 3 days' pre-treatment with verapamil
      alone (5 mg/kg, every 8 h) and during concomitant oral administration of
      cimetidine (16 mg/kg, every 8 h). Racemic verapamil and norverapamil, an active
      metabolite of verapamil, were measured by fluorescence high performance liquid
      chromatography using an achiral phenyl column. The isolated racemic verapamil was
      rechromatographed on an Ultron-OVM chiral column, which separated the two
      verapamil enantiomers. Cimetidine co-administration significantly reduced the
      systemic clearance of racemic verapamil as well as that of its enantiomers by 25
      29%. The clearance of racemic verapamil administered orally as well as that of
      its enantiomers was also reduced by 28% during cimetidine coadministration. The
      decrease in verapamil metabolism by cimetidine appeared to be non
      stereoselective. On the other hand, cimetidine co-administration had no
      significant effect on the apparent volume of distribution of racemic verapamil
      and its enantiomers or the plasma protein binding or the blood to plasma
      concentration ratio of racemic verapamil. In addition, the ratio of the area
      under the plasma concentration-time curve for norverapamil to that of verapamil
      was unaffected by cimetidine co-administration.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7629926
TI  - The disposition of gentamicin in equine plasma, synovial fluid and lymph.
AB  - Plasma (P), synovial fluid (SF) and lymph (L) concentrations of gentamicin were
      studied in two trials. A lymph vessel in the hindlimb was cannulated. The day
      after surgery (trial A), P and L samples were collected for 12 h after
      intravenous injection of gentamicin sulphate at 2.2 mg/kg dose rate.
      Approximately 48 h after surgery (trial B), the fetlock joint of the cannulated
      hindlimb was catheterized and P, SF and L samples collected for 12 h after a
      similar intravenous injection. The kinetic parameters were similar to those in
      other reports and did not differ between trials (P < 0.05). The P, L and SF
      disposition profiles were similar. The 95% confidence interval for P & L
      concentrations overlapped 2-3 h after injection. Thereafter, parallelism between
      L and P concentrations was observed, but L concentrations were on average 60%
      higher than P concentrations, and elimination from L was slower than from P. The
      mean L/SF and P/SF ratios were 1.54 +/- 0.2 and 1.25 +/- 0.2, 2-4 h after
      injection. Gentamicin elimination from SF appeared to be slower than from L and
      P. Lymph cannulation is a viable technique for antibiotic disposition studies. A
      sample of any of the fluids 3 h after injection was representative of the others.
      While SF concentrations were of limited value for predicting tissue fluid (L)
      concentrations 3-8 after injection, P concentrations were a useful index.

PMID- 7629927
TI  - Comparative pharmacokinetics of amoxicillin/clavulanic acid combination after
      intravenous administration to sheep and goats.
AB  - The pharmacokinetic behaviour of an amoxicillin/clavulanic acid combination was
      studied after intravenous administration of single doses (20 mg/kg per kg body
      weight) to five sheep and six goats. The objective was to determine whether there
      are differences between sheep and goats in the disposition of amoxicillin and
      clavulanic acid. The plasma concentration-time data were analysed by
      compartmental pharmacokinetic and non-compartmental methods. The disposition
      curves for both drugs were best described by a biexponential equation (two
      compartment open model) in sheep and goats. The elimination half-lives of
      amoxicillin were 1.43 +/- 0.16 h in sheep and 1.13 +/- 0.19 h in goats, and of
      clavulanic acid were 1.16 +/- 0.01 h and 0.85 +/- 0.09 h in sheep and goats
      respectively. The apparent volumes of distribution of amoxicillin and clavulanic
      acid were similar in the two species. Body clearances of amoxicillin were 0.09 +/
      0.01 L/h kg in sheep and 0.11 +/- 0.01 L/h kg in goats, and of clavulanic acid
      were 0.07 +/- 0.01 L/h kg and 0.12 +/- 0.01 L/h kg in sheep and goats
      respectively. The half-lives and body clearances of amoxicillin and clavulanic
      acid differed significantly between sheep and goats. It was concluded that the
      disposition of amoxicillin and clavulanic acid administered intravenously as an
      amoxicillin/clavulanic acid combination to sheep and goats differed between the
      two ruminant species. Even though the differences in disposition kinetics of both
      drugs were statistically significant, the same intravenous dosing rate of this
      antimicrobial combination can generally be used in sheep and goats.

PMID- 7629928
TI  - Antipyrine disposition in the dehydrated camel.
AB  - In the present study the effects of water deprivation in the camel (Camelus
      dromedarius) on the pharmacokinetic profile of antipyrine were assessed. A cross
      over design was used. The pharmacokinetics of antipyrine in adult and young
      camels were compared. Antipyrine was administered intravenously to young and
      adult female camels when water was available ad libitum and to the adult camels
      after 14 days of dehydration. The elimination half-life of antipyrine in watered
      adult camels was 136.5 +/- 16.7 min. The half-life of elimination and the mean
      residence time of antipyrine were significantly prolonged following dehydration.
      The observed effects of water deprivation were not a function of age, as the
      pharmacokinetic profile of antipyrine in young camels was similar to that of the
      adults, but more likely due to the changes in oxidative metabolic capacity of the
      liver as a result of a reduced general metabolism. The results of the present
      study also show that the intrinsic clearance of antipyrine is proportional to the
      camel's body weight, as previously shown for other mammalian species.

PMID- 7629929
TI  - Proteoglycan metabolism of equine articular cartilage and its modulation by
      insulin-like growth factors.
AB  - The effect of human recombinant insulin-like growth factor 1 (rhIGF-1) on
      proteoglycan (PG) metabolism of full thickness equine articular cartilage
      explants was investigated. PG synthesis was stimulated at all ages, but higher
      concentrations of rhIGF-1 were required for maximal stimulation of adult
      cartilage. There were no changes in the hydrodynamic size, electrophoretic
      heterogeneity or composition of proteoglycans isolated from rhIGF-1-stimulated
      cartilage. rhIGF-1 reduced the rate of turnover of both newly synthesized and
      endogenous proteoglycans in all ages of cartilage investigated. The structure of
      proteoglycan fragments retained within the matrix and those released into the
      culture medium was unaffected by IGF-1 stimulation, suggesting that this peptide
      is a key regulator of the proteoglycan composition of equine articular cartilage
      extracellular matrix.

PMID- 7629930
TI  - Neomycin residues in kidneys of orally dosed non-ruminating calves determined by
      high-performance liquid chromatographic and microbiological assay methods.

PMID- 7629931
TI  - The effect of a 5-hydroxytryptamine antagonist (R51703) on halothane. MAC in the
      dog.

PMID- 7629932
TI  - Pharmacokinetics of gentamicin in rabbits.

PMID- 7629933
TI  - Distribution and elimination of clenbuterol in tissues and fluids of calves
      following prolonged oral administration at a growth-promoting dose.
AB  - A pharmacokinetic study is described in which Friesian calves (n = 30) were
      treated orally with clenbuterol at 10 times the therapeutic dose. The study was
      designed to establish the distribution and elimination of clenbuterol from edible
      tissues, the major compartments of the eye and body fluids. Animals (n = 24) were
      dosed (10 micrograms/kg body weight) twice daily with clenbuterol for 21 days and
      slaughtered in groups of five (one untreated control animal per group) at 6 h and
      1, 2, 4, 8 and 16 days after cessation of treatment. At slaughter, samples of
      diaphragm muscle, liver, kidney, bile, urine and both eyes were obtained. One of
      the eyes was separated into constituent tissues: aqueous humour, vitreous humour,
      cornea, lens, retina (without pigmented epithelium), choroid (with pigmented
      retinal epithelium; choroid/PRE) and sclera. All samples were stored at -20
      degrees C. Clenbuterol concentrations were higher in liver than kidney, bile and
      urine from day 2 of withdrawal onwards. Concentrations in choroid/PRE were at
      least 10 times higher than in liver at all periods following cessation of
      treatment and 52 times higher 16 days after treatment. The concentrations of
      clenbuterol in the constituent tissues of the eye were in the order choroid/PRE >
      cornea > > retina > aqueous humour/vitreous humour > or = lens. Concentrations of
      clenbuterol in choroid/PRE taken from eyes frozen whole were generally lower than
      those in choroid/PRE separated before storage. Choroid/PRE stored by either
      method contained clenbuterol at more than 100 ng/g 16 days following cessation of
      treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7629934
TI  - Methoctramine, a cardioselective muscarinic cholinergic antagonist, prevents
      fentanyl-induced bradycardia in the dog.
AB  - A controlled study examining the effects of the cardioselective muscarinic
      cholinergic antagonist methoctramine on fentanyl-induced bradycardia was
      performed in six dogs. Five doses of methoctramine (6, 10, 20, 30 and 60
      micrograms/kg) followed by fentanyl (20 micrograms/kg) were administered randomly
      on separate days. Fentanyl caused a significant reduction in heart rate from
      baseline values. Moreover, fentanyl produced a variety of arrhythmogenic actions
      indicative of vagal hyperactivity, including sinus bradycardia, second-degree
      atrioventricular block and ventricular and supraventricular escape beats.
      Administration of methoctramine 5 min before fentanyl injection prevented the
      bradycardic effects of fentanyl in a dose-dependent manner, with high doses of
      methoctramine causing sinus tachycardia. Using regression analysis, the dose of
      methoctramine necessary to prevent fentanyl-induced bradyarrhythmias without
      causing tachycardia was calculated as 14.4 micrograms/kg. The study confirmed
      that fentanyl administration in the conscious dog causes profound bradycardia
      with bradyarrhythmias. The cardioselective muscarinic antagonist agent
      methoctramine prevented the bradycardic effects of fentanyl.

PMID- 7629935
TI  - Clinical pharmacology of cefixime in unweaned calves.
AB  - Cefixime is a unique third-generation oral cephalosporin. Its in vitro activity
      and pharmacokinetic properties have been studied to assess its potential for use
      in the therapy of newborn calf infections due to gram-negative bacteria. The
      minimum inhibitory concentrations of cefixime for 90% (MIC90) of field isolates
      of Escherichia coli, Salmonella and Pasteurella were 0.10-0.40 micrograms/mL. The
      serum disposition kinetics of cefixime following intravenous and oral
      administration was evaluated. The elimination half-life of cefixime after
      intravenous and oral administration was 3.5-4.0 h, the steady-state volume of
      distribution was 0.34 L/kg and approximately 90% of the drug was bound to serum
      proteins. Oral absorption was comparatively slow and bioavailability values for
      single 5 mg/kg doses were 20.2% after the administration of 200 mg of cefixime in
      capsules, 28.3% after dosing an aqueous solution of cefixime and 35.7% after
      fasted calves received the solution of cefixime. Mean serum drug concentrations
      12 h after the cefixime solution was administered orally (5 mg/kg) were 1.05
      micrograms/mL for the milk-fed calves and 1.76 micrograms/mL for the fasted
      calves. Computations showed that mean free drug concentrations equal to the MIC50
      of the drug for gram-negative pathogens associated with newborn calf infections
      can be maintained in tissues by multiple treatments at 5 mg/kg every 12 h or 10
      mg/kg every 24 h.

PMID- 7629936
TI  - A piece of my mind. Brad missed the miracle.

PMID- 7629937
TI  - New light on skin cancer mechanisms.

PMID- 7629938
TI  - Acellular pertussis vaccine hailed for infants.

PMID- 7629939
TI  - US military medical support continues as future of United Nations in former
      Yugoslavia is debated.

PMID- 7629940
TI  - From the Health Care Financing Administration.

PMID- 7629941
TI  - From the Centers for Disease Control and Prevention. Pertussis--United States,
      January 1992-June 1995.

PMID- 7629942
TI  - From the Centers for Disease Control and Prevention. Suicide among children,
      adolescents, and young adults--United States, 1980-1992.

PMID- 7629943
TI  - From the Centers for Disease Control and Prevention. Fatal and nonfatal suicide
      attempts among adolescents--Oregon, 1988-1993.

PMID- 7629944
TI  - Censorship of medical journals in occupied Japan.

PMID- 7629945
TI  - Error in medicine.

PMID- 7629946
TI  - Error in medicine.

PMID- 7629947
TI  - Error in medicine.

PMID- 7629948
TI  - Error in medicine.

PMID- 7629949
TI  - Error in medicine.

PMID- 7629950
TI  - Error in medicine.

PMID- 7629951
TI  - Error in medicine.

PMID- 7629952
TI  - Error in medicine.

PMID- 7629953
TI  - Telemedicine.

PMID- 7629954
TI  - The effect of zinc supplementation on pregnancy outcome.
AB  - OBJECTIVE: To evaluate whether zinc supplementation during pregnancy is
      associated with an increase in birth weight. DESIGN: A randomized double-blind
      placebo-controlled trial. SETTING: Outpatient clinic and delivery service at the
      University of Alabama at Birmingham. PATIENTS: Five hundred eighty medically
      indigent but otherwise healthy African-American pregnant women with plasma zinc
      levels below the median at enrollment in prenatal care, randomized at 19 weeks'
      gestational age. Women were subdivided by the population median body mass index
      of 26 kg/m2 into two groups for additional analyses. INTERVENTION: Women who were
      taking a non-zinc-containing prenatal multivitamin/mineral tablet were randomized
      to receive either a daily dose of 25 mg of zinc or a placebo until delivery. MAIN
      OUTCOME MEASURES: Birth weight, gestational age at birth, and head circumference
      at birth. RESULTS: In all women, infants in the zinc supplement group had a
      significantly greater birth weight (126 g, P = .03) and head circumference (0.4
      cm, P = .02) than infants in the placebo group. In women with a body mass index
      less than 26 kg/m2, zinc supplementation was associated with a 248-g higher
      infant birth weight (P = .005) and a 0.7-cm larger infant head circumference (P =
      .007). Plasma zinc concentrations were significantly higher in the zinc
      supplement group. CONCLUSIONS: Daily zinc supplementation in women with
      relatively low plasma zinc concentrations in early pregnancy is associated with
      greater infant birth weights and head circumferences, with the effect occurring
      predominantly in women with a body mass index less than 26 kg/m2.

PMID- 7629955
TI  - Use of health services by African-American children with asthma on Medicaid.
AB  - OBJECTIVE: To determine whether African-American children with asthma use more
      emergency department (ED) and inpatient medical services and fewer preventive
      services than white children with similar insurance coverage and family income.
      DESIGN: Historical cohort study during Medicaid claims data. SETTING: Aid to
      Families With Dependent Children enrollees aged 3 through 17 years in Seattle
      Tacoma, Wash, metropolitan area. PATIENTS: All 576 African-American children and
      1369 white children receiving services for asthma between June 1988 and December
      1992. MAIN OUTCOME MEASURES: Utilization of asthma services (ED, impatient,
      office visits, and pharmacy) and well-child services and associated Medicaid
      reimbursements. RESULTS: African-American children were more likely than white
      children to make ED visits or to be hospitalized for asthma; adjusted odds ratios
      (ORs) were 1.70 (95% confidence interval [Cl], 1.34 to 2.15) and 1.42 (95% Cl,
      1.03 to 1.96), respectively. African-American children were less likely to have
      made an office visit for asthma; the adjusted OR was 0.48 (95% Cl, 0.26 to 0.85).
      The two groups were similarly likely to have filled a prescription for an asthma
      medication and to have made a well-child visit. Per capita payments for asthma
      services were 24% higher for African-American children: $436 vs $350 per child
      year. CONCLUSIONS: Higher use of ED and inpatient services for asthma among
      African-American children using Medicaid (compared with white children) cannot be
      fully explained by poverty or inadequate health insurance. Furthermore, these
      children appear to make disproportionately few office visits for asthma,
      suggesting suboptimal use of preventive services for asthma. In contrast, the
      comparable use of well-child visits in the two groups suggests the problem may
      not be in access to care in general, but there may be specific problems in the
      successful management of chronic diseases such as asthma among African-American
      children.

PMID- 7629956
TI  - The relation of gastroesophageal reflux disease and its treatment to
      adenocarcinomas of the esophagus and gastric cardia.
AB  - OBJECTIVE: To examine the relationship of gastrointestinal disorders and their
      treatment to the risk of adenocarcinomas of the esophagus and gastric cardia
      (AEC). DESIGN: A medical record-based case-control study, with data collected on
      a standardized form by a trained abstractor, blind to the case-control status.
      SETTING: A large prepaid health plan. SUBJECTS: Case patients were plan members
      newly diagnosed with histologically confirmed AEC from 1986 to 1992. For each of
      the 196 eligible case patients, one control was selected who matched for
      membership at time of diagnosis, sex, year of birth, and duration of membership.
      MAIN OUTCOME MEASURES: Association between AEC and history of gastroesophageal
      conditions and their treatment. Conditional logistic regression procedures were
      used for calculation of odds ratios (ORs) and corresponding 95% confidence
      intervals (Cls), with adjustment for race, smoking status, and body mass index.
      Medications were grouped into H2 antagonists (cimetidine, ranitidine, famotidine,
      and nizatidine) and anticholinergics (propantheline bromide, dicyclomine
      hydrochloride, Donnatal [combination of atropine sulfate, hyoscyamine sulfate,
      phenobarbital, and scopolamine hydrobromide], and Librax [combination of
      chlordiazepoxide hydrochloride and clidinium bromide]). RESULTS: Significant
      twofold or greater risks of AEC were associated with a history of esophageal
      reflux, hiatal hernia, esophagitis/esophageal ulcer, and difficulty swallowing.
      The ORs increased with increasing number of these conditions. Although a fourfold
      risk was linked to four or more prescriptions for H2 antagonists, the risk was
      reduced to 1.5 (95% Cl, 0.4 to 5.4) after adjusting for the predisposing
      conditions. Further analysis revealed that the excess risk was restricted to
      persons with a history of gastroesophageal reflux and related conditions. No
      association was observed for overall use of anticholinergics. However, after
      adjustment for predisposing conditions, ORs decreased with increasing number of
      prescriptions for anticholinergics (P for trend = .08) CONCLUSIONS: This study
      provides reassuring findings that use of H2 antagonists and anticholinergics does
      not increase AEC risk. It also quantifies the elevated risk of AEC associated
      with gastroesophageal reflux disease. Further research into reflux disease and
      the production of premalignant epithelial changes may help elucidate carcinogenic
      mechanisms and measures aimed at early detection and prevention of AEC.

PMID- 7629957
TI  - The inaccessibility of advance directives on transfer from ambulatory to acute
      care settings.
AB  - OBJECTIVE: To investigate the accessibility of patients' previously executed
      advance directives during an acute hospitalization. DESIGN: Retrospective chart
      review. SETTING: A large metropolitan teaching hospital, a 514-bed skilled
      nursing facility, a geriatrics ambulatory care clinic, and a geriatrics group
      practice office. PATIENTS: One hundred fourteen geriatric patients who had
      previously executed an advance directive. MAIN OUTCOME MEASURES: The medical
      records of 180 admissions over 3 years, 1991 through 1993, were reviewed for
      documentation of patients' advance directive status. RESULTS: Twenty-six percent
      of patients who had previously executed advance directives had their directives
      recognized during their hospitalization. Of the subgroup of patients who were
      judged not to have the capacity to make medical decisions during their
      admissions, 26% (14/53) had their directives recognized. When the advance
      directive was recognized, it appeared to influence treatment decisions in 12
      (86%) of 14 cases. CONCLUSIONS: Previously executed advance directives are not
      accessible when patients are admitted to hospitals for acute illness. When such
      directives are recognized, they are used to influence medical treatment
      decisions. Further research is needed to define and overcome barriers to this
      inaccessibility.

PMID- 7629958
TI  - Physician-assisted suicide in Oregon. A bold experiment.

PMID- 7629959
TI  - Smoking bans in US hospitals. Results of a national survey.
AB  - OBJECTIVE: To examine compliance and characteristics of hospitals with tobacco
      control standards enacted by the Joint Commission of Accreditation of Healthcare
      Organizations (JCAHO). DESIGN AND SETTING: On-site national survey of hospitals
      as part of routine JCAHO accreditation visits. PARTICIPANTS: A total of 3327 US
      hospitals received site visits in 1992 and 1993 and were matched with American
      Hospital Association Annual Survey of Hospitals data. MAIN OUTCOME MEASURES:
      Compliance or noncompliance with tobacco control standards; location in a tobacco
      producing state; and organizational characteristics, including provision of
      psychiatric/alcohol-chemical dependency services. RESULTS: Two years after
      implementation, 95.6% of hospitals met the new JCAHO smoking ban standard; 90.9%
      of hospitals were in compliance with a second smoking standard requiring
      development and use of medical criteria for physician-ordered exceptions to the
      ban. Hospitals in tobacco-producing states had higher-than-average rates of
      compliance when compared with hospitals in other states. Hospitals providing
      psychiatric and/or substance abuse services had lower-than-average rates of
      compliance. CONCLUSION: This first industry-wide smoking ban has been successful.
      However, hospitals should consider evaluating the use of medical exceptions to
      this policy.

PMID- 7629960
TI  - Determinants of compliance with a national smoke-free hospital standard.
AB  - OBJECTIVE: To determine the extent of compliance with the new Joint Commission on
      Accreditation of Healthcare Organizations (JCAHO) standard requiring acute care
      hospitals to be smoke-free, and to identify predictors of adoption of smoke-free
      hospital policies. DESIGN: We conducted a survey of a national sample of acute
      care hospitals and developed a predictive model for implementation of smoke-free
      policies during multiple logistic regression. We examined numerous factors that
      might predict adoption of smoke-free policies, such as hospital characteristics,
      patient care services, and experience with smoke-free initiatives. SETTING AND
      PARTICIPANTS: A systematic 20% sample of JCAHO-accredited hospitals in the United
      States (n = 1278). Military, Department of Veterans Affairs, Indian Health
      Service, psychiatric, substance abuse treatment, and children's hospitals were
      excluded. MAIN OUTCOME MEASURE: Compliance with the JCAHO standard. RESULTS: The
      response rate was 85%. Six-five percent of hospitals were in compliance with the
      standard 16 months after it was introduced. Factors that were independently and
      positively associated with implementation of smoke-free policies were
      administrative support (odds ratio [OR], 7.82; 95% confidence interval [Cl], 2.05
      to 29.65) and inpatient smoking cessation services (OR, 1.24; 95% Cl, 1.02 to
      1.52). Factors negatively associated with implementation of smoke-free policy
      were the number of psychiatric treatment beds (OR, 0.57; 95% Cl, 0.14 to 0.81),
      number of substance abuse treatment beds (OR, 0.17; 95% Cl, 0.11 to 0.26), and
      presence of an active task force to address smoking policy (OR, 0.56; 95% Cl,
      0.40 to 0.77). CONCLUSIONS: The majority of acute care hospitals are in
      compliance with the JCAHO national smoke-free policy initiative. The standard is
      well accepted by most patients and employees. It is critical to address the
      challenges presented by special populations, such as psychiatry patients, to
      accomplish the goal of completely smoke-free hospitals.

PMID- 7629961
TI  - A 35-year-old man with epigastric pain.

PMID- 7629962
TI  - Structured advance planning. Is it finally time for physician action and
      reimbursement?
AB  - The field of advance directives has come a long way. It has further to go, and
      like other new interventions in medicine, it will continue to evolve. It probably
      is now ready for initiatives aimed at widespread use. An immediate agenda for
      action might look something like the following: (1) encouraging ambulatory care
      physicians to cosign advance care documents, (2) providing validated worksheets
      by institutions for ready office and ward use, (3) educating physicians in how to
      conduct advance planning, and (4) including advance planning discussions in
      reimbursement systems. Additional moves should include adjustment of medical law
      to reflect two categories of incompetence and further research on advance care
      planning to ensure continuing improvement.

PMID- 7629963
TI  - Smoke-free 2000. A step closer.

PMID- 7629964
TI  - A piece of my mind. Goma diary.

PMID- 7629965
TI  - Censorship of the atomic bomb casualty reports in occupied Japan. A complete ban
      vs temporary delay.

PMID- 7629966
TI  - Cancer drug may join the AIDS arsenal.

PMID- 7629967
TI  - Physicians in Missouri (but not Illinois) win battle to block physician
      participation in executions.

PMID- 7629968
TI  - New panel tackles clinical research funding cuts.

PMID- 7629969
TI  - From the Centers for Disease Control and Prevention. Trends in smoking initiation
      among adolescents and young adults--United States, 1980-1989.

PMID- 7629970
TI  - From the Centers for Disease Control and Prevention. Outbreak of acute
      gastroenteritis attributable to Escherichia coli serotype O104:H21--Helena,
      Montana, 1994.

PMID- 7629971
TI  - From the Centers for Disease Control and Prevention. Influenza and pneumococcal
      vaccination coverage levels among persons aged > or = 65 years--United States,
      1973-1993.

PMID- 7629972
TI  - From the Centers for Disease Control and Prevention. Pneumonia and influenza
      death rates--United States, 1979-1994.

PMID- 7629973
TI  - Physical activity and public health.

PMID- 7629974
TI  - Physical activity and public health.

PMID- 7629975
TI  - Physical activity and public health.

PMID- 7629976
TI  - Physical activity and public health.

PMID- 7629977
TI  - The social organization of sexuality.

PMID- 7629978
TI  - Obesity in developing nations and US weight guidelines.

PMID- 7629979
TI  - Improving the accuracy of death certificates.

PMID- 7629980
TI  - Diet and serum potassium in patients on ACE inhibitors.

PMID- 7629981
TI  - HDL cholesterol predicts coronary heart disease mortality in older persons.
AB  - OBJECTIVES: To examine the relationship of total cholesterol and high-density
      lipoprotein cholesterol (HDL-C) with coronary heart disease (CHD) mortality and
      with occurrence of new CHD events in persons aged 71 years and older. DESIGN:
      Prospective cohort study with a median of 4.4 years of follow-up. SETTING: East
      Boston, Mass; New Haven, Conn; and Iowa and Washington counties, Iowa.
      PARTICIPANTS: A total of 2527 women and 1377 men who completed an interview, had
      serum lipid determinations, and survived at least 1 year. New CHD events were
      evaluated in persons with no CHD history or hospitalization. MAIN OUTCOME
      MEASURES: Death due to CHD (ICD-9 codes 410 through 414 as underlying cause of
      death); new occurrence of CHD events (fatal CHD or hospitalization with CHD [ICD
      9 codes 410 through 414]). RESULTS: After adjustment for established CHD risk
      factors, the relative risk (RR) of death due to CHD for those with low HDL-C (<
      0.90 mmol/L [< 35 mg/dL]) compared with the reference group (HDL-C > or = 1.55
      mmol/L [> or = 60 mg/dL]) was 2.5 (95% confidence interval [CI], 1.6 to 4.0).
      Elevated risk was present in subgroups aged 71 through 80 years (RR, 4.1; 95% CI,
      1.9 to 8.8) and over 80 years (RR, 1.8; 95% CI, 0.99 to 3.4), and in men and
      women. Low HDL-C predicted an increased risk of occurrence of new CHD events (RR,
      1.4; 95% CI, 1.1 to 2.0), with similar but nonsignificant results in subgroups of
      men and women. Total cholesterol was less consistently associated with CHD
      mortality than HDL-C. When we compared individuals with total cholesterol of at
      least 6.20 mmol/L (240 mg/dL) with the reference group with total cholesterol of
      4.16 to 5.19 mmol/L (161 to 199 mg/dL), a significant risk of CHD mortality was
      seen for women (RR 1.8; 95% CI, 1.03 to 3.0) but not for men (RR, 1.0; 95% CI,
      0.5 to 2.0). In the total population, for each 1-unit increase in the total
      cholesterol/HDL-C ratio there was a 17% increase in the risk of CHD death that
      was statistically significant. CONCLUSIONS: Low HDL-C predicts CHD mortality and
      occurrence of new CHD events in persons older than 70 years. Elevated total
      cholesterol was not found to be associated with CHD mortality in older men, but
      may be a risk factor for CHD in older women.

PMID- 7629982
TI  - Azithromycin for empirical treatment of the nongonococcal urethritis syndrome in
      men. A randomized double-blind study.
AB  - OBJECTIVE: To evaluate the use of single-dose azithromycin for empirical
      treatment of nongonococcal urethritis. DESIGN: Randomized, double-blind,
      multicenter trial comparing azithromycin vs doxycycline therapy, with a 2:1
      randomization ratio. Patients were evaluated clinically and microbiologically for
      Chlamydia trachomatis and Ureaplasma urealyticum infection before therapy and at
      2 and 5 weeks after study entry. SETTING: Eleven sexually transmitted disease
      clinics throughout the United States. PATIENTS: A total of 452 men aged 18 years
      or older with symptomatic nongonococcal urethritis of less than 14 days'
      duration. INTERVENTION: Patients were treated with either 1.0 g of azithromycin
      as a single oral dose or 100 mg of doxycycline taken orally twice daily for 7
      days. MAIN OUTCOME MEASURES: Clinical resolution of symptoms and signs of
      nongonococcal urethritis, microbiological cure of C trachomatis and U
      urealyticum, and occurrence of adverse experiences. RESULTS: Of the 452 patients
      enrolled, 248 in the azithromycin-treated group and 123 in the doxycycline
      treated group were evaluable for clinical response. The two treatment groups were
      comparable in terms of age, weight, ethnic distribution, sexual preference,
      sexual activity, and history of prior nongonococcal urethritis or gonorrhea.
      Sixteen percent of the azithromycin group and 24% of the doxycycline group were
      culture positive for C trachomatis before therapy, while 38% and 28%,
      respectively, were culture positive for U urealyticum. The cumulative clinical
      cure rate was 81% (95% confidence interval [CI], 75% to 85%) in the azithromycin
      treated group and 77% (95% CI, 69% to 84%) in the doxycycline-treated group.
      Clinical cure rates in the two groups were also comparable when patients were
      stratified by presence or absence of infection with C trachomatis or U
      urealyticum prior to therapy. Among those infected with C trachomatis, overall
      microbiological cure rates were 83% (95% CI, 65% to 94%) for azithromycin-treated
      patients (n = 30) and 90% (95% CI, 68% to 98%) for doxycycline-treated patients
      (n = 21). Among those infected with U urealyticum, overall microbiological cure
      rates were 45% (95% CI, 34% to 57%) for azithromycin-treated patients (n = 75)
      and 47% (95% CI, 30% to 65%) for doxycycline-treated patients (n = 32). Adverse
      reactions were generally mild to moderate and occurred in 23% of the azithromycin
      treated group and 29% of the doxycycline-treated group. CONCLUSIONS: For
      empirical treatment of the acute nongonococcal urethritis syndrome in men, a
      single oral dose of azithromycin was as effective as a standard 7-day course of
      doxycycline in achieving clinical cure. Further, clinical cure rates were
      comparable with either regimen, regardless of the presence or absence of
      Chlamydia or Ureaplasma infection.

PMID- 7629983
TI  - Variability in brain death determination practices in children.
AB  - OBJECTIVE: To investigate variability in practices for determining brain death
      and organ procurement results in pediatric intensive care units (PICUs). DESIGN:
      Prospective cohort study. SETTING: Pediatric ICUs. PATIENTS: Children undergoing
      brain death evaluations selected from 5415 consecutive PICU admissions. MAIN
      OUTCOME MEASURES: Data from children undergoing brain death evaluations including
      number of coma examinations, number and duration of apnea tests, PCO2
      measurements at the end of the apnea test, ancillary tests used to confirm brain
      death, organ procurement, and reasons for nonprocurement. RESULTS: A total of 93
      (37%) of 248 deaths were brain deaths. Compared with the other deaths, children
      who were classified as brain dead were sicker on admission (mean Pediatric Risk
      of Mortality [PRISM] score +/- SD: 31 +/- 11 vs 23 +/- 12, P < .001; pre-ICU
      cardiopulmonary resuscitation: 72% vs 40%, P < .001), and had more traumatic
      injuries (42% vs 12%, P < .001). Variability in apnea testing included lack of
      apnea testing in 23 patients (25%) and controversial apnea testing practices in
      20 patients (22%). Three patients (3%) had brain death evaluations within hours
      of discontinuing barbiturate infusions, and four of 30 patients younger than 1
      year did not have a confirmatory test. Solid organ procurement was successful in
      32%. Reasons for nonprocurement included parental refusal (12%), disease state
      (12%), and medical examiner's case (22%). CONCLUSIONS: Substantial variability
      exists in the criteria used by clinicians for the diagnosis of brain death. Some
      practices are contradictory to the Guidelines for the Determination of Brain
      Death in Children and to recommendations for apnea testing. Organ procurement
      could be improved by increased medical examiner cooperation.

PMID- 7629984
TI  - Natural history of HIV-1 cell-free viremia.
AB  - OBJECTIVE: To characterize the natural history of viremia with human
      immunodeficiency virus type 1 (HIV-1) and its association with disease
      progression from infection to acquired immunodeficiency syndrome (AIDS). DESIGN:
      Prospective cohort study. Annual specimens were tested for quantitative virion
      associated HIV-1 RNA, p24 antigen, and CD4+ lymphocyte levels. PARTICIPANTS: A
      total of 42 homosexual men who seroconverted to HIV-1 between 1982 and 1985. MAIN
      OUTCOME MEASURES: Trends over time in serum HIV-1 RNA level, correlations between
      serum HIV-1 RNA and other markers, and prediction of AIDS using these markers.
      RESULTS: HIV-1 RNA levels were stable over time, increasing by 10-fold or more in
      only six (14%) of the 42 subjects during 3 to 11 years of follow-up. Mean HIV-1
      RNA levels were 10(3.8) copies/mL if AIDS occurred in less than 4 years, 10(3.07)
      copies/mL if AIDS developed within 4 through 9 years, and 10(2.27) copies/mL if
      AIDS did not develop within 6 through 11 years. In both univariate and
      multivariate models, initial and subsequent HIV-1 RNA levels, p24 antigenemia,
      and percentage of CD4+ lymphocytes were independently predictive of AIDS.
      CONCLUSIONS: The stability of virion-associated HIV-1 RNA levels suggests that an
      equilibrium between HIV-1 replication rate and efficacy of immunologic response
      is established shortly after infection and persists throughout the asymptomatic
      period of the disease. Thus, defective immunologic control of HIV-1 infection may
      be as important as the viral replication rate for determining AIDS-free survival.
      Because individual steady-state levels of viremia were established soon after
      infection, HIV-1 RNA levels may be useful markers for predicting clinical
      outcome.

PMID- 7629985
TI  - Community-based prevalence of anal incontinence.
AB  - OBJECTIVE: To determine the prevalence of and characteristics associated with
      anal incontinence in the general community. SETTING: Community survey.
      PARTICIPANTS: The population of the state of Wisconsin sampled in the Wisconsin
      Family Health Survey. Subjects were identified by random digit dialing with
      telephone interview. The individual within each household identified as most
      knowledgeable about the health status of all other members of the household was
      asked about the health status of each member of the household. Approximately 200
      households were surveyed each month. MAIN OUTCOME MEASURES: The presence of anal
      incontinence to solid or liquid feces or gas, who suffered from it, the frequency
      of anal incontinence, and how the incontinent person coped with it. RESULTS: A
      total of 2570 households comprising 6959 individuals were surveyed, and 153
      individuals were reported to have anal incontinence, representing 2.2% of the
      population (95% confidence interval [Cl], +/- 0.3%). Thirty percent of the
      incontinent subjects were older than 65 years, and 63% were women. Of those with
      anal incontinence, 36% were incontinent to solid feces, 54% to liquid feces, and
      60% to gas. In a multivariate analysis, independent associations of the following
      risk factors with anal incontinence were found: female sex (odds ratio [OR], 1.5;
      Cl, 1.1 to 2.1), age (continuously adjusted) (OR, 1.01; Cl, 1.01 to 1.02),
      physical limitations (OR, 1.8; Cl, 1.2 to 2.7), and poor general health (OR, 1.6;
      Cl, 1.4 to 1.9). CONCLUSIONS: Anal incontinence was reported in 2.2% of the
      general population. Independent risk factors for incontinence include female sex,
      advancing age, poor general health, and physical limitations.

PMID- 7629986
TI  - The poisoned patient with altered consciousness. Controversies in the use of a
      'coma cocktail'.
AB  - OBJECTIVE: In the assessment and management of the potentially poisoned patient
      with altered consciousness, the most consequential and controversial
      interventions occur during the first 5 minutes of care. In this review article,
      the risks and benefits of standard diagnostic and therapeutic interventions are
      presented to guide clinicians through this critical period of decision making.
      DATA SOURCES: Data for discussion were obtained from a search of English-language
      publications referenced on MEDLINE for the years 1966 to 1994. Older literature
      was included when pertinent. Search terms included poisoning, overdose, toxicity,
      naloxone, glucose, thiamine, and flumazenil. STUDY SELECTION: Only large trials
      were used for determinations of diagnostic utility and efficacy. Small trials,
      case series, and case reports were reviewed extensively for adverse effects. DATA
      EXTRACTION AND SYNTHESIS: Trials were reviewed for overall methodology, inclusion
      and exclusion criteria, sources of bias, and outcome. CONCLUSION: Analysis favors
      empirical administration of hypertonic dextrose and thiamine hydrochloride to
      patients with altered consciousness. Although rapid reagent test strips can be
      used to guide this therapy, they are not infallible, and they fail to recognize
      clinical hypoglycemia that may occur without numerical hypoglycemia.
      Administration of naloxone hydrochloride should be reserved for patients with
      signs and symptoms of opioid intoxication. Flumazenil is best left for reversal
      of therapeutic conscious sedation and rare select cases of benzodiazepine
      overdose.

PMID- 7629987
TI  - Users' guides to the medical literature. VIII. How to use clinical practice
      guidelines. A. Are the recommendations valid? The Evidence-Based Medicine Working
      Group.

PMID- 7629988
TI  - Cholesterol and coronary heart disease in older adults. No easy answers.

PMID- 7629989
TI  - Evolving strategies for management of the nongonococcal urethritis syndrome.

PMID- 7629990
TI  - [Molecular biological mechanism of cancer metastasis and the prediction of
      metastasis in clinical cases].
AB  - An outline of the mechanism of cancer metastasis is presented from a molecular
      biological point of view, and the present state and future possibility of
      prediction about cancer metastasis in clinical cases is described. Cancer
      metastasis is developed through multiple steps. With the progress of studies on
      the mechanism of metastasis, the effort to predict cancer metastasis in clinical
      cases has progressed. Metastasis is formed in concern with many factors, so it
      may be highly difficult to explain clinical metastasis by a single factor. It
      will be important to comprehensively put many factors into consideration. For the
      preoperative diagnosis of the potential of metastasis, examination of specimens
      from endoscopic biopsy or blood serum will become more important.

PMID- 7629991
TI  - [The structure and function of cadherins and their pathophysiological roles in
      diseases].
AB  - Cadherins are a family of Ca(2+)-dependent cell adhesion molecules that mediate
      cell adhesion by homophilic interaction and play critical role in multicellular
      organ formation. Recent progress revealed the three-dimensional structure of
      extracellular cadherin repeats that made great progress in the study of cell
      adhesion by cadherins. The perturbation of cadherin function in transformed cells
      results in inhibition of cell-cell adhesion, that appears to promote metastasis
      and invasiveness of tumor cells. Expression as well as modifications of catenins,
      which link cadherins to cytoskeletons, have crucial effects on this purturbation
      mechanisms. Tyrosine phosphorylation of cadherin catenin complex may be the
      important regulatory mechanism.

PMID- 7629992
TI  - [Increased cell adhesiveness and decreased tumorigenicity induced in human colon
      carcinoma cells by transfection with E-cadherin cDNA].
AB  - Metastasis of colon carcinomas is assumed to be caused by multiple steps, which
      include a loss of cell adhesion that results in the release of carcinoma cells
      from the original tumor tissue. A human colon carcinoma cell line was established
      from a poorly differentiated metastatic adenocarcinoma without cell-cell adhesion
      and without expression of E-cadherin mRNA. To this cell line, mouse E-cadherin
      cDNA in a expression vector was co-transfected with a neomycin-resistant gene.
      The transfected cells, which expressed exogenous E-cadherin gene, showed a
      compact shape with strong cell-cell adhesion and with increased cell-substratum
      adhesion. These cells showed a significantly low anchorage independency and
      decreased invasiveness compared to the parental carcinoma cells. Their growth
      rate was decreased both in vitro and in the subcutis of nude mice.

PMID- 7629993
TI  - [Dysfunction of E-cadherin due to mutation of beta-catenin in a scirrhous gastric
      cancer cell line].
AB  - E-cadherin is a calcium dependent cell-cell adhesion molecule. In cancer tissue,
      detachment of the adhesion system is indispensable for invasion and metastasis of
      cancer cells. We have investigated mechanism of the dysfunction of E-cadherin
      dependent cell-cell adhesion system in gastric carcinoma cells. Although the high
      expression of E-cadherin in a scirrhous gastric cancer cell line HSC-39, the
      function of E-cadherin was completely abolished. Western blotting of beta-catenin
      in HSC-39 cells demonstrated that a truncated beta-catenin was detected. The
      truncation was due to partial deletion of beta-catenin DNA. It was concluded that
      in HSC-39 loss of E-cadherin dependent cell-cell adhesion was due to mutation of
      beta-catenin gene.

PMID- 7629994
TI  - [Abnormal expression of E-cadherin in human pancreatic carcinoma cell lines].
AB  - Nineteen human pancreatic cancer cell lines were analyzed for possible abnormal
      mRNA and/or protein expression of the E-cadherin. Five lines showed no or
      markedly reduced expression of the E-cadherin, and protein was absent. In 9
      lines, mRNA was positive but protein distribution was abnormal, i.e. diffusely
      positive in cytoplasm instead of membrane, or mixed distribution to membrane and
      cytoplasm. These 14 cell lines with abnormal E-cadherin expression grow in
      isolated fashion or loose sheet formation, indicating the loss of cell-cell
      adhesion system. These findings that the strong relation between E-cadherin
      abnormalities and loss of physical cell-cell interaction may explain the
      extensively poor prognosis of the patients with pancreatic carcinoma.

PMID- 7629995
TI  - [Correlation between the intercellular adhesion molecule (E-cadherin) and its
      associated protein (alpha-catenin) expression and metastasis in human digestive
      cancers].
AB  - The immunostaining (ABC method) of E-cadherin and alpha-catenin were performed on
      46 esophageal cancers, 67 gastric cancers, 100 colon cancers. E-cadherin and
      alpha-catenin expression was evaluated as preserved and reduced according to the
      proportion of positive cells, respectively. The reduction of alpha-catenin
      expression was more significantly related to lymph node metastasis than that of E
      cadherin. Furthermore, the frequency of hematogenous liver metastasis in
      preserved E-cadherin expression and reduced alpha-catenin expression was
      significantly higher than that in another combination of E-cadherin and alpha
      catenin expression, in gastric and colon cancer. The reduction of alpha-catenin
      expression was associated with declined intercellular adhesiveness, which
      occasionally was not accompanied by reduction of E-cadherin. Therefore, the
      expression of alpha-catenin might more sensitively indicated cell-cell adhesion,
      predicting tumor metastasis.

PMID- 7629996
TI  - [Abnormal E-cadherin expression as a risk factor for deep myometrial invasion and
      lymph node metastasis in endometrial carcinoma].
AB  - We examined expression of E-cadherin cell-cell adhesion molecule, which is
      supposed to have invasion-suppressing activity, in 53 cases with endometrial
      carcinoma. Fresh frozen sections were immunostained with a mouse monoclonal
      antibody to human E-cadherin (HECD-1). E-cadherin expression was inversely
      correlated with grade of tumor (p = 0.0267), depth of myometrial invasion (p =
      0.0146) and pelvic and paraaortic node metastases (p = 0.0184 and p = 0.0419,
      respectively). Multivariate analysis revealed that among histologic grade,
      nuclear grade, and E-cadherin expression, E-cadherin expression was most strongly
      correlated with depth of myometrial invasion (p = 0.0491). These results suggest
      that decreased expression of E-cadherin facilitates invasion of endometrial
      carcinoma.

PMID- 7629997
TI  - [Expression of E-cadherin as related to prognostic factors and survivals in
      breast cancer].
AB  - E-cadherin (E-CD) expression and its clinicopathological implication were
      investigated in 26 patients with breast cancer by immunohistochemical staining.
      12 out of 26 primary lesions (46%) express strong and homogeneous expression of E
      cadherin (preserved type), while in 14 cases (54%), degree of E-CD expression was
      reduced, i.e., 8 patients with heterogeneous staining, 2 cases with weak but
      homogeneous, and 4 cases with lost expression of E-CD (reduced type). However,
      there was no statistically significant correlation among decrease of E-CD
      expression, histological features, and advanced stages of breast cancer. Analysis
      on survivals showed better prognosis in the group with preserved E-CD expression
      than without E-CD (follow up was more than 96 months or until death). These
      findings suggests that the patients with decreased E-CD expression may be
      associated with metastasis resulting in poor prognosis, and E-CD expression could
      be one of the prognostic factors.

PMID- 7629998
TI  - [Expression of E-cadherin in thyroid neoplastic tissues and its correlation with
      malignant and metastatic potential].
AB  - Cadherin is an Ca2+ dependent adhesion molecules, which contribute to cell-cell
      adhesion and maintenance of tissue structures. Its decrease or functional
      abnormality plays an important vole in cancer invasion and metastasis. We
      investigate the expression of E- cadherin in thyroid neoplasms (papillary cancer,
      follicular cancer, medullary cancer anaplastic cancer and follicular adenoma) and
      normal thyroid. The decrease of E-cadherin expression in thyroid cancer
      correlates with its malignancy and metastatic potentiality.

PMID- 7629999
TI  - [Subclassification, molecular structure, function and ligand in integrin
      superfamily].
AB  - Integrins are the major family of cell surface receptors that mediate adhesion to
      the extracellular matrix and sometimes cell-cell adhesive interactions. These
      integrin-mediated adhesive interactions are involved in the regulation of many
      cellular functions, including embryonic development, tumor cell growth and
      metastasis, programmed cell death, hemostasis, inflammation, immune reaction,
      bone reabsorption, etc. Integrins are composed of alpha and beta transmembrane
      subunits selected from among 16 alpha and 8 beta subunits that heterodimerize to
      produce more than 20 different receptors which bind specific ligands. Ligand
      binding sites have been clarified by chimera integrin protein in some integrins.
      Integrins link to intracellular cytoskeletal complexes and bundles of actin
      filaments. There have been many reports about intracellular signaling pathways
      activated by integrin-ligand interactions.

PMID- 7630000
TI  - [Integrins involved in tumor invasion and metastasis].
AB  - The process of tumor growth and metastasis is a complex cascade of events
      relating many factors. The adhesion molecules relate to the cell-cell adhesion,
      adhesion to the extracellular matrix or the vascular endothelium and are thought
      to play important roles in the invasion and metastasis of the cancer. Integrins
      are known as extracellular matrix receptors. The change in the expression of
      integrins in the cancer cells has been reported. Recent information on the role
      of integrins in tumor progression and metastasis is reviewed here.

PMID- 7630001
TI  - [Analysis of the mechanism of tumor metastasis by the transfection of integrin
      cDNA].
AB  - Integrin plays an important role in tumor metastasis through its interaction with
      extracellular matrix and endothelial cell. We have examined the role of each
      integrin in tumor metastasis by using transfection of integrin cDNA into various
      cells. Transfection of integrin alpha 2 subunit into RD cells, human
      rhabdomyosarcoma cells which do not express integrin alpha 2 beta 1, potentiated
      the frequency of metastases in various organs; lung, bone, adrenal gland, lymph
      node. alpha 4-transfectant of Chinese hamster ovary (CHO) cells, which do not
      have alpha 4 beta 1 on the cell surface, metastasized to bone through its
      interaction with VCAM-1 in the bone marrow stroma cells. On the other hand, alpha
      5-transfectant of CHO cells was much less tumorgenic than parent CHO cells. These
      data suggest integrin influence tumor metastasis sometimes favorably and
      sometimes unfavorably according to the activity and the balance of various
      integrins.

PMID- 7630002
TI  - [Role of tripeptide Arg-Gly-Asp (RGD) on adhesiveness of human pancreatic cancer
      cell, PANC-1 to extracellular matrix].
AB  - Tumor cell invasion and metastasis are likely to be complex processes involving a
      variety of cell surface receptors mediating interactions with a number of
      extracellular matrix molecules, including fibronectin, laminin, and collagen. We
      have applied this interaction of receptors for specific adhesive substrates in
      vitro, using specific monoclonal antibody and biologically active synthetic
      peptides with human pancreatic carcinoma cell, PANC-1. Tripeptide Arg-Gly-Asp
      (RGD) inhibited adhesion on PANC-1 cells to fibronectin but less effective in
      blocking adhesion to laminin and collagen, although anti beta 1-integrin antibody
      significantly inhibited adhesion of fibronectin but less inhibited to laminin,
      collagen. Our studies emphasize the importance of synthetic tripeptide RGD in
      adhesion on PANC-1 to extracellular matrix protein, as well as indicating the
      specificity of cell surface receptor, beta 1 integrin.

PMID- 7630003
TI  - [Inhibition of tumor metastasis by synthetic peptide analogues of cell-adhesive
      RGD sequence of fibronectin].
AB  - Since the adhesive interaction between tumor cells and host cells, or
      extracellular matrix (ECM), presumably plays a crucial role in metastatic
      formation, we used synthetic or recombinant polypeptide analogues, poly (RGD), CH
      271 or SCM-chitin-RGDS based on Arg-Gly-Asp (RGD) sequence. Poly (RGD)
      effectively inhibited the experimental lung and liver metastasis when coinjected
      i.v. with different types of tumors. In a spontaneous lung metastasis model using
      B16-BL6 melanoma, multiple administrations of this polypeptide, before or after
      surgical excision of the primary tumor, resulted in significant inhibition of
      tumor metastasis. The mechanism responsible for the inhibition is partly
      associated with the ability to interfere with cell functions such as
      adhesiveness, motility, and invasiveness in the process of metastasis. CH-271
      fusion polypeptide was much more effective in inhibiting lung or liver metastasis
      of tumors than cell-binding domain (C-274) or heparin-binding domain (H-271)
      polypeptides. SCM-chitin-RGDS conjugate significantly reduced the number of tumor
      colonies in the lungs by coinjection with Colon 26 carcinoma as compared with
      either RGDS or SCM-chitin alone. Since the polypeptides derived from cell
      adhesion molecules showed no toxicity to the host, they may provide a promising
      approach for the control of cancer metastasis.

PMID- 7630004
TI  - [Integrin expression and ability to adhere to extracellular matrix and
      endothelial cells in human lung cancers].
AB  - Tumor cell interaction with extracellular matrix and endothelial cells constitute
      the most crucial factor of metastasis. Integrins are one of adhesion molecules
      which mediate the interaction. Most lung cancers adhered strongly to
      extracellular matrix corresponding with expression of integrins. Three lung
      cancers which expressed few or no integrins had very weak ability to adhere to
      extracellular matrix. Strong binding to endothelial cells was found in most lines
      but the three lung cancers had very little ability to adhere to endothelial
      cells. Binding to endothelial cells were strongly inhibited by antibodies to beta
      1 subunit. Lung cancers may adhere to extracellular matrix and endothelial cells
      through integrins, especially the beta-1 subfamily.

PMID- 7630005
TI  - [Possible significance of VLA-4 (alpha 4 beta 1) for hematogenous metastasis of
      renal cell cancer].
AB  - Very late antigen-4 (VLA-4) composed of alpha 4 and beta 1, a member of the beta
      1-integrin subfamily, facilitates cell-to-cell interaction with vascular cell
      adhesion molecule-1 (VCAM-1) on endothelial cells (EC). Attachment of blood-borne
      tumor cells to EC is a crucial step for hematogenous metastasis, and VLA-4
      positive tumor cells can attach to EC by binding to VCAM-1. Renal cell cancer
      (RCC) reveals proportionally greater percentage of metastasis among other
      carcinomas at an initial diagnosis. We investigated whether VLA-4 is expressed on
      RCC and how such expression on RCC correlates with metastatic potential of RCC.
      Immunohistochemical staining on 66 primary and 4 metastatic RCCs showed that 4 of
      4 metastatic and 5 of 8 primary RCCs (72.5%) from patients with lung and/or brain
      metastasis expressed alpha 4 and beta 1 chains. On the other hand, 13 of 58
      (22.4%) RCCs without metastasis expressed alpha 4 chain. alpha 4 and beta 1
      expressions were also detected on 5 of 5 human RCC cell lines by flowcytometer
      analysis. RT-PCR followed by Southern blot hybridization also confirmed mRNA
      production in 4 of 5 RCC cell lines. Furthermore, adhesion of alpha 4-positive
      RCC cell lines to human umbilical vein endothelial cells (HUVECs) was augmented
      by a treatment of HUVECs with Tumor necrosis factor-alpha (TNF-alpha) or IL-4
      thorough increase of VCAM-1 expression. These adhesion were inhibited by anti
      alpha 4 or anti-VCAM-1 antibodies suggesting that VLA-4-VCAM-1 interaction was
      involved in the adhesion between RCC cells and HUVECs.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7630006
TI  - [Association between expression of integrin (VLA-3, VLA-5) and malignancy in
      human colon-cancer].
AB  - The expression of the VLA-integrins beta 1, -2, -3, -5, -6 and alpha v beta 3 was
      studied immunohistochemically in the tissue sample from human colon-cancer.
      Furthermore, histological stage-grouping of the colon-cancer (I-V), additional
      vascular invasion such as lymphatic and blood-vessel invasion, was made to
      express the malignancy of the carcinoma, for making a comparison with the
      expression of the integrins. Immunohistologically, beta 1, VLA-2, and alpha v
      beta 3 were mildly expressed in the carcinoma cells and VLA-6, markedly
      expressed. These findings were not correlated with the malignant stage-grouping.
      For VLA-3, the carcinoma showed mild to marked expression with a diffuse
      distribution on the cell surface in the peripheral area of the carcinoma, nearly
      correlating with the histological stage of malignancy. While, the expression of
      VLA-5 was almost absent in the carcinoma. These results suggest that the enhanced
      expression of VLA-3 with suppressed expression of VLA-5 is functionally important
      for the carcinoma cell invasion and also for the metastasis.

PMID- 7630007
TI  - [Comparison of the pattern of integrin expression between primary tumors and
      liver metastasis of gastric and colorectal cancers].
AB  - To investigate the interrelationship between integrin VLA3 overexpression and
      liver metastasis, immunohistochemical studies of VLA3 were made in 73 cases of
      gastric cancer (66 cases without liver metastasis, 7 cases with liver metastasis)
      and 15 cases of colorectal cancer (3 cases without liver metastasis, 12 cases
      with liver metastasis). The rate of integrin VLA3 expression in 69 primary
      gastric and colorectal cancers without liver metastasis was 41%, that was higher
      than that (0%) in the 19 primary tumors of gastric and colorectal cancers with
      liver metastasis. In contrast, the positive rate for integrin VLA3 staining in 19
      cases involving liver metastasis of gastric and colorectal cancers was 58%
      (11/19), which was higher than that (0%) in primary tumors. These findings
      suggest that VLA3 may play an important role in the process of liver metastasis
      of gastric and colorectal cancers.

PMID- 7630008
TI  - [The role of CD44 adhesion molecules].
AB  - CD44 is a transmembrane glycoprotein involved in the interaction between cells
      and extracellular matrix. CD44 is ubiquitously expressed on cells, and has been
      thought to be a cell adhesion molecule with proposed functions in extracellular
      matrix binding, cell migration and lymphocyte homing. In 1991, Stamenkovic et al.
      showed the existence of two forms of CD44: a hematopoietic (standard) and an
      epithelial form which was highly expressed by carcinomas. The alternative
      splicing of 10 variant exons encoding the membrane proximal portion of the
      external domain of CD44, in particular, results in many variant isoforms. These
      may play a critical role in malignant behavior and in determining organ
      specificity in metastasis.

PMID- 7630009
TI  - [Abnormal transcription of cell adhesion molecule CD44 in human gastric
      carcinomas].
AB  - CD44 abnormal transcription in gastric carcinomas is overviewed. The
      overexpression of aberrant CD44 transcripts detected by RT-PCR/Southern blot
      hybridization method is a common genetic event in gastric carcinomas regardless
      of the histological type or clinicopathological stage. In addition, six out of
      nine (66.7%) well differentiated or intestinal type gastric cancers overexpressed
      more than three aberrant transcripts, whereas ten out of eleven (90.9%) poorly
      differentiated or diffuse type cancers overexpressed single or two lower
      molecular weight variants. These results indicate that the detection of CD44
      transcription variants can serve as a powerful tool for the diagnosis of gastric
      cancer. It is also suggested from the difference in variant expression pattern
      that the well differentiated and the poorly differentiated type gastric
      carcinomas have different genetic pathways.

PMID- 7630010
TI  - [Expression of CD44 metastatic variant mRNA in colorectal carcinomas and its role
      in tumor metastasis and invasion].
AB  - The expression of CD44 molecules was investigated in colorectal carcinomas by RT
      PCR and Southern Blot Analysis. There were significant differences between
      neoplastic and non-neoplastic colonic mucosa in the expression of CD44 metastatic
      variant mRNA. The CD44 metastatic variant mRNA was found to be increased in the
      neoplastic mucosa. However, we could not find metastasis-specific transcript in
      primary colorectal carcinomas. Our study suggests that the neoplastic
      transformation of colonic mucosa increases the expression of CD44 molecules,
      including the variant forms, which modulate the behavior of the tumor cells. The
      measurement of serum CD44 is useful in the estimation of tumor mass and its
      regression by treatment. Further investigation is needed to clearly understand
      the role of CD44 molecules in tumor metastasis and invasion.

PMID- 7630011
TI  - [Expression of CD44 alternative splicing variants in lung cancer].
AB  - Expression of isoforms of the CD44 is generated by alternative splicing of CD44
      gene; CD44H: lacks all 10 alternative exons, CD44R: the alternative exons v8 to
      v10, CD44V: other group of variants which contains the alternative exon v6. In
      some tumors such as colorectal cancer, breast cancer, non-Hodgkin lymphoma, and
      melanoma, over-expressed CD44 isoform which contains such alternative-spliced
      variant exons may play a causative role in tumor metastasis. In lung cancer,
      however, the role of CD44 variants in tumor progression and metastasis is
      uncertain. In our study and reported literature, no definite correlation was
      observed between the expression of specific CD44 isoform and tumor progression or
      metastasis of lung cancer.

PMID- 7630012
TI  - [Expression of CD44 variant form in human renal cell carcinoma].
AB  - To examine whether renal cell carcinoma display altered CD44 expression we
      performed reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of
      CD44 in the tissues resected from 19 patients with renal cell carcinoma and 6
      renal cancer cell lines. To detect the CD44 variants, we utilized the RT-PCR
      Southern blot method reported by Matsumura et al. In 12 of 17 (70.6%) cases,
      about a 700 base pairs band was emphasized in cancerous tissues compared with
      normal kidney. Moreover, we found that this isoform is the CD44 variant sharing
      only exon v10. Examination by Northern blot analysis has revealed that all tumors
      express a higher level of CD44 variants sharing exon v10. Our findings suggest
      that this variant form plays some roles in renal cell carcinoma.

PMID- 7630013
TI  - [Expression of CD44 in endometrial cancer and metastasis].
AB  - We have examined expression of CD44 in 17 normal endometria and 58 endometrial
      carcinomas by reverse transcription and polymerase chain reaction (RT-PCR) and by
      immunohistochemistry using antibodies to CD44. CD44 variants were expressed in 13
      out of 17 (76.5%) normal endometria, whereas 11 out of 58 (19.0%) endometrial
      carcinomas. Furthermore, lymph-vascular space involvement of cancer cells was
      observed to be statistically significant in the CD44 negative group as opposed to
      the positive group. Immunohistochemical examination revealed that intense
      staining in normal endometria was seen on the gland cells at the basement
      membrane side. CD44 may have a role in the function of normal endometrium such as
      implantation, and CD44 might be related with metastasis of endometrial cancer
      cells through lymph-vascular space.

PMID- 7630014
TI  - [Structures, synthesis and functions of sialyl Le(a)/sialyl Le(x) antigens].
AB  - Sialyl Lewis a/sialyl Lewis x antigens, which panels of monoclonal antibodies can
      recognize, are synthesized by a series of glycosyltransferases. Especially, alpha
      (1,3)/(1,4) fucosyltransferases and/or alpha(2,3)sialyltransferases regulate
      expression patterns temporally and spatially, such as in epithelium of digestive
      systems or in leukocytes. The carbohydrate ligands of P-selectin and E-selectin
      have been identified as sialyl Lewis x expressed on granulocytes, monocytes, and
      natural killer cells. Expression of sialyl Lewis x on these cells is mainly
      determined by Fuc-TVII, but as for the counterparts of sialyl-transferases, there
      remains much uncertainty. P-selectin-dependent adhesion of tumor cells and E
      selectin-dependent adhesion of tumor cells to endothelial cells play some role
      for tumor cell aggregation leading to microembolism and hematogenous metastasis
      of cancers. We have found expression of some fucosyltransferases (Fuc-TIII, VI,
      VII) and a sialyltransferase (ST3O) are increased in colon cancer tissues
      coincidentally with sialyl Lewis a antigens, with which E-selectin can interact.
      As already started in many laboratories, genetic manipulation of glycosylation
      pathways in gene-targeted animals has an outstanding potential to yield clues to
      oligosaccharide function.

PMID- 7630015
TI  - [Glycosyltransferase genes for synthesis of Lewis antigens].
AB  - Biosynthetic pathways of Lewis antigens with type 1 and type 2 chains were
      described on the molecular genetic basis of glycosyltransferases involved in
      synthesis of the antigens. The analysis of Lewis-gene (Le gene) genotyping
      revealed that the Le gene is responsible not only for synthesis of Lewis antigens
      on erythrocytes (Le(a) and Leb antigens) but also for synthesis of the Lewis
      antigens with type 1 chain, Le(a), Leb and sLea antigens, in digestive organs.
      Among an a1,3 fucosyltransferase family, FucT VI is a candidate more responsible
      for synthesis of sLex antigen in intestinal cancer cells than the other a1,3
      fucosyltransferases. Molecular genetic analysis on Se gene is now under progress
      to distinguish the genotypes of Le (a+ b-) individuals from Le(a- b+) individuals
      in the Japanese population. Individual polymorphism of Lewis antigens is
      determined by point mutations of glycosyltransferase genes, as proved in ABO, Le,
      Se, H and FucT VI genes, involved in biosynthetic pathways of the antigens.

PMID- 7630016
TI  - [Abnormal expression of carbohydrate chain and its mechanism in endometrial
      cancer].
AB  - An increased rate of expression of Lewis group antigens, particularly Lewisb
      antigen, was observed in endometrial cancers compared with its expression in
      normal endometria. In order to elucidate the expression mechanism of Lewisb
      antigen in endometrial cancer, the level of fucosyltransferase (FT) was examined.
      The levels of alpha 1-2FT alpha 1-3FT and alpha 1-4FT were higher in endometrial
      cancer than those in normal endometrium. Endometrial cancer with a poor prognosis
      tended to react poorly to anti-endometrial cancer monoclonal antibody designated
      MSN-1, suggesting the possibility that the reactivity to MSN-1 is useful as a new
      prognostic factor for endometrial cancer. Cells of uterine endometrial cancer
      cell line SNG-II were classified into two groups according to their reactivity
      with MSN-1, whose antigen recognized is mainly Lewisb antigen. Using these
      classified cells of endometrial cancer cell line, it has revealed that the cells
      which strongly express H type antigen have more tendency to attach to endothelial
      cells and to cause metastasis than the cells which strongly express Lewisb
      antigen.

PMID- 7630017
TI  - [Mechanism of blood-borne metastasis in relation to the interaction between
      pancreatic carcinoma and endothelial cells].
AB  - We investigated the interaction between pancreas carcinoma and endothelium, using
      the originally established human pancreas carcinoma cell lines (PCI), and
      reported the importance of E-selectin and sialyl Lewis(a) in the adhesion of
      pancreas carcinoma cells to endothelium activated by inflammatory cytokines.
      Interestingly, the attachment of PCI to endothelial cells was augmented by
      preincubation of PCI with endothelial cells through an upregulated E-selectin
      expression on endothelial cells. Major factor of this activity was IL-1 alpha
      which was produced by pancreas carcinoma cells. We supposed that tumor-derived IL
      1 alpha may contribute to the hematogenous metastasis of cancers in non-inflamed,
      distant location. In addition to IL-1 alpha, IL-6 also was produced by some, but
      not all, of PCI cell lines. An endothelial permeability was increased only when
      endothelial cells were pretreated with the culture supernatant of IL-6-producing
      cell lines. The activity of supernatant was inhibited by specific antibody
      reactive for IL-6. Using a liver metastatic model in the nude mouse, we
      investigated the importance of sialyl Lewis(a) expression and IL-6 production by
      pancreas carcinoma for progression of metastasis in vivo. Sialyl Lewis(a)
      positive cell lines generated more numerous metastatic colonies in the liver than
      sialyl Lewis(a)-negative cell lines did. PCI lines that produce IL-6 generated
      significantly less metastases in both number of liver nodules and incidence
      itself than IL-6-producing PCI did, therefore, surface expression of sialyl
      Lewis(a) and production of IL-6 appear to be important modulators that regulate
      hematogenous metastasis of pancreas carcinoma.

PMID- 7630018
TI  - [Immunohistochemical expression of sialyl-Lewis antigens in lung cancer].
AB  - We investigated the immunohistochemical expression of three carbohydrate
      antigens, sialyl-Lewisa, sialyl-Lewisx and sialyl-Lewisx-i, in human lung cancer
      tissues using monoclonal antibodies, 2D3, SNH3 and FH6, respectively, and
      compared the expression rate of these three antigens with clinical and pathologic
      findings. The expression rate of all the three antigens in adenocarcinoma was
      higher than that in squamous cell carcinoma and that of sialyl-Lewisx was highest
      in adenocarcinoma. Sialyl-Lewisx antigen was expressed in all cases of positive
      nodal metastasis or postoperative distant metastasis in adenocarcinoma. In
      squamous cell carcinoma, however, there was no relationship between the
      expression rate of sialyl-Lewisx antigen and nodal or distant metastasis. These
      results suggest that expression of sialyl-Lewisx antigen in adenocarcinoma of the
      lung may be correlated with nodal or distant metastasis.

PMID- 7630019
TI  - [Fucosyltransferase producing sialyl Le(a) and sialyl Le(x) carbohydrate antigen
      in gastrointestinal cancer].
AB  - Sialyl Lea and sialyl Lex are cancer-associated carbohydrate antigens. The
      biosynthesis of these antigens is completed by fucosyltransferases. We measured
      the activity of alpha 1-->4 fucosyltransferase (sialyl Lea synthase) and alpha 1-
      >3 fucosyltransferase (sialyl Lex synthase) in gastrointestinal cancer tissues.
      alpha 1-->4 fucosyltransferase activity was similarly detected in most normal or
      malignant tissues. alpha 1-->3 fucosyltransferase activity in gastric cancer was
      higher than in the normal mucosa. In colonic cancer, although the enhanced
      expression of sialyl Lex was observed in 86% of cases, the elevated activity of
      alpha 1-->3 fucosyltransferase was observed in only 58%. In conclusion, the
      expression of sialyl Lea and sialyl Lex antigens in the stomach and colon was not
      controlled solely by fucosyltransferases.

PMID- 7630021
TI  - [Molecular biology of matrix metalloproteinases (MMPs) and tissue inhibitors of
      metalloproteinases (TIMPs), and the regulation of these genes in tumor tissues].
AB  - Degradation of the extracellular matrix (ECM) is required for tumor invasion and
      metastasis. Matrix metalloproteinases (MMPs), which degrade the various ECM
      components, are thought to play key roles in these processes. The activity of
      MMPs is strictly controlled at the following three steps, gene expression,
      proenzyme activation and inhibition by tissue inhibitors of metalloproteinases
      (TIMPs). Overexpression of MMP genes and ECM degrading activities have reported
      to be associated with the invasive and metastatic tumor cells. Many researchers
      have been reported that these phenotypes of tumor cells were inhibited by TIMPs.
      Thus, the potential of tumor cells to invade into the ECM is regulated by the
      balance of MMPs and TIMPs.

PMID- 7630020
TI  - [Suppression of lung metastasis of B16 mouse melanoma cells by introduction of N
      acetylglucosaminyltransferase III gene].
AB  - The beta 1-6 structure of N-oligosaccharides, formed by beta 1-6 N
      acetylglucosaminyltransferase (GnT-V), is associated with metastatic potential.
      We established a highly metastatic subclone, B16-hm, from low metastatic B16-F1
      murine melanoma cells. Introduction of the gene for beta 1-4 N
      acetylglucosaminyltransferase (GnT-III) into B16-hm murine melanoma cells reduced
      the level of beta 1-6 structure by competing for the substrate, resulting in the
      suppression of lung metastasis in both syngeneic and nude mice, decreased
      invasiveness into the matrigel, and inhibition of cell attachment to collagen and
      laminin without affecting cell growth. The gene transfection altered the N
      oligosaccharides of membrane glycoproteins, as measured by L-PHA and E-PHA
      binding. Our results demonstrated a causative role for beta 1-6 branches in the
      metastasis by gene transfection.

PMID- 7630022
TI  - [TIMPs (tissue inhibitors of metalloproteinases): their species, functions and
      effects on tumor metastasis].
AB  - TIMPs (tissue inhibitors of metalloproteinases) belong to a family composed of
      three members: TIMP-1, -2 and -3. They possess a high degree similarity in their
      structure including 12 conserved cystenyl residues at the same relative
      positions. Recently, they have been shown to inhibit not only proteolytic
      activities of metalloproteinases but also tumor cells metastasis in vitro and in
      vivo. In this review, we summarize their structure information, inhibitory
      mechanism of metalloproteinases, TIMPs-like secretory inhibitors, other
      biological functions of TIMPs such as growth-regulating activity, their
      chromosomal localizations and related diseases. We also mention their inhibitory
      effects on tumor cells metastasis in vitro and in vivo, and their clinical
      applications.

PMID- 7630023
TI  - [The expression of MMPs and TIMPs in human breast cancer tissues and importance
      of their balance in cancer invasion and metastasis].
AB  - Tumor cells degrade extracellular matrix components (ECM) to invade surrounding
      tissues. Malignant tumor cells are known to produce various ECM-degrading enzymes
      including matrix metalloproteinases (MMPs), serine proteinases and cathepsins.
      Among them, MMPs may play a key role in cancer invasion and metastasis. To study
      the role of MMPs in the progression of human breast carcinomas, we examined
      production and tissue localization of MMP-1, MMP-2, MMP-3, MMP-9 and their common
      inhibitors, tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2). The data
      suggest that the imbalance between MMPs and TIMPs produced by tumor tissues may
      be a determinant of the progression in breast carcinoma.

PMID- 7630024
TI  - [Significance of MMP-9 and TIMP-1 production during liver metastasis in
      colorectal cancer].
AB  - We have investigated the expression of matrix metalloproteinase 9 (MMP-9) and
      tissue inhibitor of metalloproteinases 1 (TIMP-1) in colorectal cancer by the
      immunostaining (avidin-biotin peroxidase complex method) and in situ
      hybridization (ISH). Both MMP-9 enzyme and messenger RNA (mRNA) for MMP-9 were
      located in tumor cells, neutrophils, monocyte-macrophages and fibroblasts in
      colorectal cancer tissue. The location of TIMP-1 mRNA was similar to that of MMP
      9 mRNA in colorectal cancer tissue. There was a strong correlation between the
      expression of MMP-9 in tumor cells and liver metastasis. The expression of mRNA
      for TIMP-1 in stromal cells in cases associated with liver metastasis was
      significantly higher than that in cases without liver metastasis. However, in
      tumor cells, predominant expression of MMP-9 mRNA was observed in all cases
      associated with liver metastasis. These results suggest that MMP-9 might play an
      important role in hematogenous metastasis in colorectal cancer and that the
      balance between the production of MMP-9 and TIMP-1, in particular in tumor cells,
      is important as one of the pathogenesis of tumor metastasis.

PMID- 7630025
TI  - [Increased expression of gelatinases A and B, matrilysin and TIMP-1 genes in
      human malignant gliomas ].
AB  - Malignant glioma is a local invasive tumor in the central nervous system. The
      mRNA expression of five matrix metalloproteinases (MMPs) and two tissue
      inhibitors of metalloproteinases (TIMPs) was examined in surgical specimens of
      three brain tissues, two astrocytomas, four anaplastic astrocytomas and eleven
      glioblastomas, including recurrent one anaplastic astrocytoma and two
      glioblastomas. In the control brain tissues, mRNA expression was high for TIMP-2,
      low for gelatinase A and TIMP-1, and undetectable for gelatinase B, interstitial
      collagenase, stromelysin and matrilysin. Gelatinase B and TIMP-1 were
      concomitantly overexpressed in primary glioblastomas. In addition, the average
      expression level of gelatinase A increased 3.0 fold in astrocytomas and
      anaplastic astrocytomas and 6.0 fold in glioblastomas, compared to the brain
      tissues. Matrilysin was induced variably in more than half of the primary
      glioblastomas, and interstitial collagenase was slightly induced in some primary
      and recurrent glioblastomas. Stromelysin was characteristically not expressed in
      any gliomas, and the expression level of TIMP-2 did not significantly change in
      the gliomas. These results suggest that the concomitant increased expression of
      gelatinase A, gelatinase B and occasional matrilysin genes is associated with the
      malignancy of gliomas and accompanied by the increased expression of TIMP-1 gene.

PMID- 7630026
TI  - [Expression of membrane-type matrix metalloproteinase (MT-MMP) and activation of
      MMP-2 in lung cancer].
AB  - In this study, we investigated the correlation between the expression of MMP-2
      and lymph node metastasis by analyzing 58 cases of primary lung cancer.
      Furthermore we studied expression of membrane-type MMP (MT-MMP) which was
      identified as an activator of MMP-2 and its relation to the activation ratio of
      MMP-2 in tumor tissues. Activated form of MMP-2 was detected specifically in the
      tumor tissues by zymography, and the activation ratio was significantly higher in
      20 cases of the lymph node metastasis positive group than in other 38 cases.
      Additionally, northern blott analysis showed that MT-MMP was overexpressed in
      cancer tissues and that the expression of MT-MMP was closely related to the
      amount of activated form of MMP-2. These results indicated that MMP-2, which is
      activated by MT-MMP expressed on the surface of tumor cells, play a role in tumor
      metastasis by degrading surrounding basement membranes.

PMID- 7630027
TI  - Thermal conditions in the bathroom in winter and summer, and physiological
      responses of the elderly during bathing.
AB  - Thermal conditions in the bathroom and physiological responses were examined
      during winter and summer. The subjects were 22 male and 20 female elderly people,
      between 65 and 88 years old living in 25 houses in Gunma Prefecture, Japan. Heart
      rate, blood pressure, skin temperature and thermal sensation were measured during
      bathing. Changes in thermal sensation due to bathing were assessed in the living
      room and dressing room on a 9-point scale. Then they were asked about the
      purposes of bathing and the facilities of bathroom and dressing room. The results
      are summarized as follows: 1. The purpose of bathing in winter was to warm up for
      more than 80% of the subjects. In summer, all subjects felt refreshed by bathing.
      Eighty-five percent of the subjects took a bath every other day in both seasons.
      2. Fifty-two percent of the bathrooms had no ventilating fans and 32% had no
      exclusive dressing rooms. 3. The average room temperature in the dressing rooms
      was 13-14 degrees C in winter. Thermal sensation was 'cool', 'slightly cold' or
      'cold' for more than two-thirds of the subjects when they were partially nude,
      and there were no heaters in most dressing rooms. 4. The heart rate increased
      steadily, and reached a maximum value in a partially dressed condition in both
      seasons. 5. In winter, a marked increase of systolic blood pressure was observed
      in the partially nude condition. There was a significant difference between the
      before bathing condition and partially nude condition in winter.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7630028
TI  - [A study on the effects of physical load on high school baseball players during
      midsummer games].
AB  - This study attempted to measure the physical load on high school baseball players
      during games played under extremely hot and humid conditions in the summer. The
      factors used to determine physical load were the following: body weight, oral
      temperature, blood pressure, heart rate, and serum biochemical elements. These
      were measured before and after the game. One hundred twenty-six baseball players
      from 7 high schools participated in this study. All the games were played under
      conditions of high temperature 34 degrees Celsius dry-bulb, 26 degrees Celsius
      wet-bulb, 41 degrees Celsius black-globe, 30 degrees WBGT, which are likely to
      cause heat-related illnesses. The results were as follows. 1) The physical load
      of baseball players during the game showed a 1.8 percent decrease in average body
      weight due to perspiration, a 0.35 degrees C increase in oral temperature and an
      increase in the heart rate. Examination of the serum biochemical elements showed
      that muscle deviation ferment changed due to muscular activity and blood
      condensed due to perspiration. The physical load levels of baseball players were
      influenced more by extreme heat than by exercise during the game. 2) The group of
      starting players showed higher body weight loss, oral temperature, heart rate,
      blood condensation and muscle deviation ferment levels than the group of players
      on the bench due to the difference in the length of exposure to summer heat and
      the amount of physical exertion. The changes in physical load levels during the
      game for the group of starting players were greater than those for the group for
      players on the bench. 3) Considering the changes in body weight, blood
      condensation and muscle deviation ferment, we can say that physical loads of
      players differed according to their positions, the pitcher having the greatest
      load, followed in descending order by the catcher, infielders, and outfielders.
      It has been recommended that high school baseball players should take different
      kinds of rest depending on their positions in order to recover from fatigue as
      soon as possible after a game.

PMID- 7630029
TI  - [Mechanisms of cold-induced pulmonary hypertension in rats].
AB  - The objectives of the present study are to directly measure the pulmonary and
      systemic arterial pressures in unanesthetized, and unrestrained rats during
      exposure to cold and to assess pulmonary vascular responsiveness to
      administration of the alpha-and beta-adrenergic receptor antagonists
      phenoxybenzamine (1mg/kg, i.v.) and propranolol (20 micrograms/kg, i.v.), during
      exposure to cold. Furthermore, the rats underwent long-term exposure to cold, and
      pulmonary arterial pressure, systemic arterial pressure, heart rate, arterial
      blood gases and colonic temperature were measured. A special hand-made catheter
      filled with heparinized saline was inserted into the pulmonary artery via the
      right jugular vein, the right atrium and the right ventricle. Mean pulmonary
      arterial pressure was elevated during cold exposure for 2 hours. Arterial blood
      oxygen tension slightly decreased and carbon dioxide tension slightly rose under
      these conditions. The increase in cold-induced pulmonary arterial pressure was
      significantly lower after the administration of propranolol, but there was no
      change after the administration of phenoxybenzamine. However, after
      administrating the alpha-adrenergic blocking agent a resultant increase in heart
      rate and fall in systemic arterial pressure during cold exposure prevented our
      evaluation of the pulmonary circulatory changes. These results show that beta
      adrenergic responsiveness of pulmonary vascular smooth muscle may have a role in
      the maintenance of cold-induced pulmonary hypertension.

PMID- 7630030
TI  - [A case control study of risk factors for Japanese cedar pollinosis].
AB  - Risk factors for Japanese cedar pollinosis including past or family history of
      allergic diseases, smoking and passive smoking, dwelling conditions, and life
      events were analyzed by a case control method. Patients with Japanese cedar
      pollinosis (22 males and 67 females) were matched with a corresponding number of
      patients without potential symptoms of pollinosis according to sex and age (+/- 5
      years). The mean age was 39 years in both groups. The odds ratio (OR) was
      calculated by McNemar's method and the conditional logistic regression model. The
      design and methodology in this study were somewhat inadequate so that the
      validity of the results is limited. The most important problem was no-matching
      according to exposure to pollen. Significantly high OR for past history of
      allergic disease (8.80, 95% confidence interval (CI); 3.49-22.2), atopic
      sermatitis (9.00, 95% CI; 1.14-71.0), and a sibling history of allergic disease
      (3.25, 95% CI; 1.06-9.97) were consistent with former genetical studies. ORs were
      lower than unity for current smokers (0.36, 95% CI; 0.11-1.13) and those smoking
      10 cigarettes/day or more (0.20, 95% CI; 0.04-0.91) relative to nonsmokers. The
      OR for passive smoking from 7-15 years of age as a result of the father's smoking
      habit (0.38, 95% CI; 0.17-0.86) was also significantly low. Smoking was suggested
      to increase the level of total and antigen-specific IgE in serum by former
      studies, so that sensitization and symptoms should be studied separately. The
      high OR of residents in a business or light industrial area (5.00, 95% CI; 1.45
      17.3) suggested an association with air pollution.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7630031
TI  - [Differential patterns of the number and proportion of blood leukocytes following
      endurance exercise of moderate, strenuous and severe conditions].
AB  - A study was conducted to elucidate the acute effects of endurance exercise on
      white blood cells by setting three conditions of different intensity and
      duration; (a) an upper limit of aerobic exercise for health promotion and (b)
      superior limits within endurance exercise tolerance for untrained persons were
      prescribed separately for the same healthy untrained male student volunteers (n =
      10) at intensities of 85% and 95% of the individual anaerobic threshold (AT)
      values for 1 h and 1.5 h, respectively, on a bicycle ergometer. In addition, (c)
      participants in a 100-km marathon race (n = 20) who continued running for 10-13 h
      were examined. Every condition caused significant leukocytosis due to predominant
      neutrophilia and, to a minor degree, a significant increase in monocyte number,
      the magnitude of which depended on the severity of endurance workload and
      persisted even 1 h after the termination of exercise. Simultaneously, microscopic
      evaluation of blood smears revealed the occurrence of an increased proportion of
      band neutrophils and a decreased proportion of hypersegmented neutrophils (shift
      to the left) following exercise in condition (b) but not in (a), suggesting that
      neutrophils are mobilized partly from the bone marrow reserve to the circulation.
      On the other hand, peripheral lymphopenia was observed after the termination of
      endurance exercise. These phenomena closely mimicked the known effects of
      exogenous glucocorticoid administration, suggesting an association with
      endogenous stress hormone (cortisol) secretion following strenuous
      exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7630032
TI  - A study on urine cotinine for the evaluation of smoking cessation.
AB  - Two branch offices of enterprise T in the same city engaged in service and sales
      were selected at random for this study on the evaluation of smoking cessation
      education using the urine cotinine concentration (U-Cot) measured by ion pair
      reversed-phase high performance liquid chromatography (IP-R-HPLC). Branch A
      conducted a smoking cessation education program; branch B did not. By comparison
      of the results obtained from questionnaires and U-Cot analyses at both the
      offices, we investigated the validity of evaluation by U-Cot. The results were as
      follows: I. Smokers 1. At branch A, a self-reported 20-year-old female non-smoker
      was confirmed to smoke about 5 cigarettes per day by her high concentration
      (292.8) of U-Cot at pre-education. 2. At branch A, the self-reported average
      number of cigarettes smoked daily (ANCSD) at 6 months post-education showed a
      significant decrease in comparison with that at pre-education. 3. At branch A, U
      Cot at post-education showed a significant decrease in comparison with those at 2
      weeks, 2 months, and 6 months pre-education in descending order. 4. Two male
      subjects who were strongly suspected to have submitted a false number of
      cigarettes smoked prior to urine sampling (NCSPU)/ANCSD self-reports at 6 months
      post-education were confirmed to have done so by the U-Cot values at the fourth
      period, which were in excess of 500, and the discrepancy between the ratio
      ([value at post-education in 6 months] divided by [value at pre-education]) of U
      Cot (1.52, 1.47, respectively) and that of NCSPU/ANCSD, (0.00)/0.00). 5. At
      branch A, discrepancies between the success rate of quitting smoking in self
      reported NCSPU/ANCSD at 6 months (17.0%) and in U-Cot (12.2%) were observed. At
      branch B, no such discrepancies were observed. 6. At branch A, office workers at
      6 months post-education who had, but not those who had not, previously considered
      the health damage caused by smoking showed a significant decrease in NCSPU/ANCSD,
      and also in U-Cot at 2 weeks, 2 months and 6 months post-education. At branch B,
      no such differences were observed. 7. At branch A, office workers at 6 months
      post-education who had previously considered quitting smoking showed a
      significant decrease in NCSPU/ANCSD, and also in U-Cot at 2 weeks, 2 months and 6
      months post-education. Those who had not previously considered quitting showed a
      significant decrease in ANCSD, but not in NCSPU or U-Cot.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 7630033
TI  - The association between parents' unemployment and birthweight in Japan.
AB  - The association between birthweight and parents' occupations was examined with
      the 1985 Japanese Vital Statistics, which recorded 1,419,465 live births
      delivered in Japan from April 1985 through March 1986. The mean birthweights
      [MBWs] were significantly different according to the paternal occupation as well
      as the maternal occupation after adjusting for the infants' sex and parity. The
      MBWs of children of unemployed fathers were significantly lighter than those of
      offspring of employed fathers. This was due to both retarded intrauterine growth
      and a shortened gestational period. By contrast, the MBWs were not affected by
      the unemployment of mothers. The possible reasons for the decreased MBW in the
      case of unemployed fathers were economical problems due to unemployment, less
      favorable characteristics of demography and obstetrics, and psycho-social stress
      among the wives of the unemployed.

PMID- 7630034
TI  - [The effects of long-term intake of restricted calcium, vitamin D, and vitamin E
      and cadmium-added diets on various organs and bones of mice: a histological and
      the roentgenological study].
AB  - The toxic effects of long-term administration of cadmium (Cd) on the kidneys,
      liver, and hind leg bones were studied histologically and roentgenologically in
      29-day-old female ICR-strain mice separated into groups variously fed 1) a
      commercial (calcium [1.17%], vitamin D [220IU/100g], vitamin E [10mg/100g]) diet,
      2) a low Ca (0.18% diet, 3) a low Ca and low D (50IU/100g) diet, and 4) a low Ca,
      low D and low E (5mg/100g) diet. Though the levels of vitamin D and vitamin E
      were designed to be low in each diet, their amounts fulfilled the nutritional
      requirements. Three subgroups in each category were fed Cd at dietary
      concentrations of 0, 20 or 40 ppm. After 12, 18 or 24 months on these diets the
      mice were sacrificed. 1) In the groups fed the commercial diet containing Cd,
      prominent swelling of the glomerulus and thickening of the basement membrane of
      glomerulus were observed. This did not occur in the groups fed the commercial
      diet without Cd. 2) In the groups fed the Cd-added low-Ca diet the following
      findings were more prominent compared with the low-Ca diet group. In the kidneys,
      swelling of the glomerulus, hyaline casts in tubular lumina and cellular
      infiltration of the interstitial tissue were present. In the liver, cellular
      infiltration on the interstitial tissue were present. In the liver, cellular
      infiltration of the interstitial tissue occurred. In the hind leg bones, thinning
      of trabeculae and ossification of the Achilles's tendon were seen. 3) In the Cd
      added low-Ca, D diet groups, there was atrophy of glomerulus, thickening of
      basement membrane of glomerulus, and atrophy of tubular epithelial cells in the
      kidneys, while in the liver, binuclate cells, anisonucleosis and enlargement of
      Kupffer cells were seen. In the hind leg bones, thinning of the cortex and
      trabeculae were present. All of these findings were more prominent in this group
      than in the low-Ca, group. 4) In the Cd-added low-Ca, D, E, diet groups subjects
      the following findings were more prominent than in the low-Ca, D, E, diet group.
      In the kidneys, there was swelling of glomerulus and in the liver, there were
      binuclate cells, anisonucleosis, and cellular infiltration into interstitial
      tissue. In the hind leg bones, thinning of the cortex and trabeculae, a decrease
      of cartilage cells and a decrease of osteocytes were seen. These histological and
      roentgenological changes were seen to increase in a dose-dependent manner with
      the amount of dietary Cd.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7630035
TI  - [Relationships between biting force and the morphology of the maxilloface].
AB  - The maximum biting force of 40 male students aged 26.1 +/- 3.9 years was assessed
      to evaluate the relationships between biting force and the morphology of the
      maxilloface. The evaluations were made using roentgenographic cephalogram
      measurements and oral model measurements. The results obtained were as follows.
      1. The subjects who had strong maximum biting force (MBF) were those with high
      posterior facial height, high posterior inferior facial height, long length from
      the Ar-Me line to the gonion, and long length between the adhesion of the
      masseteric muscles. 2. The subjects who had strong MBF had a small gonial angle,
      and their occlusal plane and mandibular plane approached the anterior cranial
      base and eye-ear-plane, that is, the subjects with strong MBF were considered to
      be persons with a deep overbite. 3. There was a significant positive correlation
      between MBF and discrepancy values using oral model measurements (p < 0.01). No
      significant correlations were noted between MBF and the sum of teeth size. 4.
      There was a significant positive correlation between MBF and maximum grip
      strength (p < 0.01), back strength (p < 0.01) and the long jump (p < 0.05), and
      there was a significant negative correlation between MBF and 50m running (p <
      0.01), but no significant correlations were noted between MBF and 1500m running.

PMID- 7630037
TI  - Studies on acyl-CoA: cholesterol acyltransferase (ACAT) inhibitory effects and
      enzyme selectivity of F-1394, a pantotheic acid derivative.
AB  - (1s,2s)-2-[3-(2,2-Dimethylpropyl)-3-nonylureido]aminocyclohe xane-1-yl 3-[N
      (2,2,5,5-tetramethyl-1,3-dioxane-4-carbonyl)amino]propionate (F-1394), a
      pantotheic acid derivative, is a newly synthesized inhibitor of acyl
      CoA:cholesterol acyltransferase (ACAT). In the present study, we investigated the
      inhibitory effects of F-1394 on the activities of ACAT. F-1394 reduced the ACAT
      activities in rat liver microsomes, homogenate of rabbit small intestinal mucosa
      and lysate of J774 macrophages with IC50 values of 6.4 nM, 10.7 nM and 32 nM,
      respectively. The kinetic studies showed that F-1394 exerted competitive-type
      inhibition, and the Ki values in liver and small intestinal ACAT were 4.0 nM and
      9.9 nM, respectively. The inhibitory effects of F-1394 on the activity of ACAT
      were more potent than that of other ACAT inhibitors or hypolipidemic agents. The
      study on enzyme selectivity indicated that F-1394 did not affect 3-hydroxy-3
      methylglutaryl CoA reductase, acyl-CoA synthetase and cholesterol esterase. F
      1394 weakly inhibited the activity of lecithine:cholesterol acyltransferase
      (LCAT) originating from rat plasma. The inhibitory potency of F-1394 for the
      activity of liver microsomal ACAT was 4,690-fold stronger than that for the
      activity of LCAT. These findings indicate that F-1394 is a potent and selective
      inhibitor of ACAT, and its inhibition manner is the competitive type.

PMID- 7630036
TI  - Studies on serotonin (5-HT)3-receptor antagonist effects of enantiomers of
      4,5,6,7-tetrahydro-1H-benzimidazole derivatives.
AB  - We assessed the 5-HT3-receptor antagonist effects of 4,5,6,7-1H-benzimidazole
      compounds which are derivatives of YM060, a potent and selective 5-HT3-receptor
      antagonist, in isolated guinea pig colon. YM114 (KAE-393), YM-26103-2, YM-26308-2
      (3 x 10(-9) to 3 x 10(-8) M) produced concentration-dependent shifts to the right
      of the dose-response curves for both 5-HT and 2-methyl-5-HT (2-Me-5-HT). YM114
      (pA2 = 9.08 against 5-HT, pA2 = 8.88 against 2-Me-5-HT), YM-26103-2 (pA2 = 8.27
      against 5-HT, pA2 = 8.19 against 2-Me-5-HT), and YM-26308-2 (pA2 = 8.58 against 5
      HT, pA2 = 8.4 against 2-Me-5-HT) showed similar pA2 values irrespective of the
      agonist used, suggesting that they have 5-HT3-receptor blocking activity
      irrespective of the N-position at the aromatic ring. Since these compounds have
      an asymmetric center, their enantiomers exist. The S-isomers were one to three
      orders of magnitude less potent than the respective R-isomer compounds,
      indicating that the stereochemical configuration of 4,5,6,7-tetrahydro-1H
      benzimidazoles is an important determinant of their affinity for 5-HT3 receptors.
      These results suggest that the highly potent 5-HT3 receptor antagonism and high
      selectivity for 5-HT3 receptors of 4,5,6,7-tetrahydro-1H-benzimidazole
      derivatives are conserved irrespective of the position of the nitrogen atom in
      the aromatic ring and that 5-HT3 receptors favor the R-isometric conformation of
      these compounds.

PMID- 7630038
TI  - A study of ambrein treatment for the evaluation of change in plasma biochemical
      parameters in rats.
AB  - Biochemical effects of acute and subacute treatments with ambrein were
      investigated in rats by measuring the total proteins, cholesterol, triglycerides,
      GOT, GPT and alkaline phosphatase in the blood plasma. Also, determinations of
      prothrombin time (PT), partial thrombin time (PTT), thrombin time (TT) and
      fibrinogen level were performed. Furthermore, changes in plasma electrolyte
      concentration were studied. Ambrein administered i.p. did not cause any toxic
      symptoms in the liver as revealed by the histology of the liver tissue both in
      acute and subacute treatments. Ambrein itself did not significantly affect the
      plasma protein, cholesterol, GOT and GPT profiles, but lowered alkaline
      phosphatase at high doses (50 and 250 mg/kg) after subacute treatment. Thus far,
      no specific pattern of action of ambrein in electrolyte control has been found.
      However, it increased PT, PTT and TT and decreased fibrinogen levels in both the
      acute and subacute studies, pointing towards its potential as an anticoagulant
      and antifibrinogenic agent.

PMID- 7630039
TI  - A supplemental measure of stay-times in the light box on step-through passive
      avoidance.
AB  - The avoidance behavior of rats in a typical step-through passive avoidance task
      was evaluated by using two types of time measurements that differed from
      traditional step-through latency (STL). The total stay-time in the light box (TL)
      was calculated as an index of the dark box avoidance throughout the retention
      trial, counting the time before and after the first step-through. The total stay
      time in the far area of the light box (TF) was calculated as an index of the
      tendency to keep away from the dark box. TL, TF and the STL increased with
      electrical shock intensity at acquisition trials and gradually decreased through
      an extinction procedure. The discrepancy between our new measures and the STL was
      observed when the effects of a new drug, RS-8359, which was reported to
      ameliorate ischemic brain damage, were examined in ischemic animals. TL, TF and
      STL decreased in rats receiving brain ischemia, and we found that after treatment
      with RS-8359, TL and TF increased, but no effect was observed on STL. The
      discrepancy observed suggests that a short STL does not necessarily imply a loss
      of avoidance behaviour. Passive avoidance tests can be more revealing about a
      drug's effects when stay-time measures are used.

PMID- 7630040
TI  - A study on dilazep: I. Mechanism of anti-ischemic action of dilazep is not
      coronary vasodilation but decreased cardiac mechanical function in the isolated,
      working rat heart.
AB  - In the isolated, perfused working rat heart, ischemia (15 min) decreased the
      mechanical function and the tissue levels of adenosine triphosphate and creatine
      phosphate and increased the levels of lactate and free fatty acids. Reperfusion
      (20 min) did not restore the mechanical function, but restored incompletely the
      levels of metabolites, with the exception of free fatty acids, which increased
      further during reperfusion. Dilazep was given 5 min before starting ischemia
      until the end of ischemia. Dilazep at 5 or 10 microM decreased the cardiac
      mechanical function, but did not affect coronary flow in the pre-ischemic heart.
      Dilazep at 5 or 10 microM accelerated the recovery of mechanical function and
      coronary flow during reperfusion, and it attenuated metabolic changes induced by
      ischemia and reperfusion. Dilazep at 1 microM neither decreased the pre-ischemic
      mechanical function nor restored the mechanical function during reperfusion,
      although it attenuated the accumulation of free fatty acids during reperfusion.
      These results suggest that dilazep attenuates both ischemia- and reperfusion
      induced myocardial damage and that the anti-ischemic action of dilazep is not due
      to coronary vasodilation but probably due to an energy-sparing effect and other
      effects that remain to be studied.

PMID- 7630041
TI  - A study on dilazep: II. Dilazep attenuates lysophosphatidylcholine-induced
      mechanical and metabolic derangements in the isolated, working rat heart.
AB  - The effects of dilazep, d-propranolol and lidocaine on the mechanical and
      metabolic changes induced by lysophosphatidylcholine (LPC) were studied in
      isolated, perfused working rat heart. After a stabilization period, the heart was
      perfused for 5 min with LPC (10 microM) alone, LPC plus dilazep (5, 10 or 20
      microM), LPC plus d-propranolol (30 or 50 microM) or LPC plus lidocaine (30 or
      100 microM) and then perfused with normal Krebs-Henseleit bicarbonate (KHB)
      buffer for a further 20 min. Perfusion with LPC for 5 min followed by KHB for 20
      min irreversibly decreased cardiac mechanical function, decreased the tissue
      levels of adenosine triphosphate and creatine phosphate significantly, and
      increased the tissue levels of lactate and free fatty acids including arachidonic
      acid. Dilazep or d-propranolol significantly attenuated the mechanical and
      metabolic changes induced by LPC, but lidocaine did not. These results indicate
      that the exogenous LPC causes ischemia-like changes, suggesting that LPC is one
      of the important factors in producing ischemia-reperfusion derangements in terms
      of mechanical and metabolic functions, and that both dilazep and d-propranolol
      can prevent the LPC-induced myocardial damage.

PMID- 7630042
TI  - Oxytocin-induced natriuresis mediated by the renal kallikrein-kinin system in
      anesthetized male rats.
AB  - Intravenous infusion of oxytocin (OT) (10-100 nmol/kg/30 min) to 8-week-old
      anesthetized male rats resulted in a dose-dependent increase in urine volume,
      which showed a peak value 30-45 min after the start of OT-infusion. Urinary
      excretions of sodium, chloride and potassium were also increased by OT, showing
      peak values at 30-45 min, without any increase in the creatinine level. The
      natriuresis by OT was accompanied by increased excretion of urinary active
      kallikrein, which showed a peak value 15 min after the start of OT-infusion. The
      urinary kinin level was also increased. Intravenous infusion of a kallikrein
      inhibitor, aprotinin (15 mg/kg/90 min), when started 30 min before the OT
      infusion, significantly inhibited the OT-induced increase in urine volume and
      urinary excretion of sodium, chloride and potassium. Intravenous infusion of a
      bradykinin B2 antagonist, Hoe 140 (D-Arg[Hyp3,Thi5,D-Tic7,Oic8]BK, 4.5 mg/kg/90
      min), when started 30 min before the OT-infusion, significantly inhibited the OT
      induced increases in urine volume and urinary excretion of sodium and chloride,
      but not that of potassium. These results indicate that the OT-infusion induces
      natriuresis in male rats, and more than half of the natriuresis is mediated by a
      concomitant increase in excretion of urinary active kallikrein and the kinin
      generated.

PMID- 7630044
TI  - Vasodilative effect of adrenomedullin in isolated arteries of the dog.
AB  - Adrenomedullin is known to induce profound hypotension in vivo, but the direct
      effect of this peptide on isolated arteries has not been demonstrated. This study
      estimated the vasodilative effects of adrenomedullin in comparison with those of
      calcitonin gene-related peptide (CGRP) in basilar, mesenteric, coronary, renal
      and femoral arteries isolated from the dog. Adrenomedullin (3 to 100 nM) and CGRP
      (1 to 30 nM) induced concentration-dependent relaxation of these arteries with
      and without endothelium, and the relaxing effects were slightly greater in
      endothelium-intact arteries than in denuded ones. The vasodilative potency of
      adrenomedullin relative to CGRP was smaller in the femoral artery than in
      basilar, mesenteric, coronary and renal arteries.

PMID- 7630043
TI  - Inhibitory effect of clopidogrel, vapiprost and argatroban on the middle cerebral
      artery thrombosis in the rat.
AB  - This study investigated the roles of thromboxane A2 (TXA2), ADP and thrombin in
      middle cerebral artery (MCA) thrombosis in the rat. The rat MCA was occluded by a
      thrombus induced by the photochemical reaction of rose bengal by green light that
      causes endothelial damage followed by platelet adhesion, aggregation and
      formation of a platelet and fibrin-rich thrombus at the site of the photochemical
      reaction. Vapiprost, a specific TXA2-receptor antagonist; clopidogrel, which has
      the thienopyridine structure of ticlopidine and is a more potent inhibitor of ADP
      induced platelet aggregation than ticlopidine; argatroban, a specific thrombin
      inhibitor; or heparin was administered intravenously before rose bengal
      injection. The MCA local blood flow was monitored by a laser Doppler flowmeter.
      The MCA was occluded by thrombus about 5 min after the initiation of the
      photochemical reaction. Vapiprost, clopidogrel and argatroban all significantly
      prolonged the time taken for the thrombotic occlusion of the MCA, but in this
      respect, heparin was ineffective. Our observations suggest that vapiprost and
      clopidogrel are useful antithrombotic agents against platelet and fibrin-rich
      thrombi. The effect of argatroban is attributable to inhibition of thrombin
      induced platelet activation and fibrin generation. The thrombosis model described
      in this study is useful for understanding the mechanism(s) of thrombogenesis in
      the rat MCA and may be applied to other mammalian species.

PMID- 7630045
TI  - Inhibitory effect of AL-3264, a new antiallergic agent, on the Prausnitz-Kustner
      reaction and leukotriene production in monkeys.
AB  - To clarify the antiallergic effect and antiallergic mechanism of AL-3264 (N-[4-[4
      (diphenylmethyl)-1-piperazinyl]butyl]-3-(6-methyl-3- pyridyl)acrylamide) in
      monkeys, its effects on the Prausnitz-Kustner (P-K) reaction, the histamine skin
      reaction and leukotriene production were examined. In contrast to ketotifen and
      mepyramine, AL-3264 inhibited the P-K reaction, which is mainly mediated by
      leukotriene and histamine, more clearly than the skin reaction evoked by
      histamine alone. AL-3264 also inhibited the leukotriene (LT) production in the
      broncho-alveolar cells, suggesting that the inhibition of LT production actually
      contributes to the antiallergic effect of AL-3264.

PMID- 7630047
TI  - President's message: focusing on the system.

PMID- 7630046
TI  - Selective blockade of P-type calcium channels by lead in cultured hippocampal
      neurons.
AB  - The effects of lead ions (Pb2+) on neuronal calcium channels were examined in
      cultured hippocampal neurons. Pb2+ blocked calcium channels in a concentration
      dependent manner. The current-voltage relationship of the inhibition suggested a
      selective blockade of high-threshold calcium channels by Pb2+ up to a
      concentration of 3 microM. Pb2+ (3 microM) preferentially suppressed the omega
      agatoxin IVA-sensitive components of the calcium channels. These findings suggest
      that Pb2+ mainly affects the P-type calcium channels at low concentrations.

PMID- 7630048
TI  - Getting the word out about nursing: opportunities with the ER show and SANE
      programs.

PMID- 7630049
TI  - Where did all the nurses go? The need to capture nursing.

PMID- 7630050
TI  - More on moral evaluation of patients study.

PMID- 7630051
TI  - A 28-year-old man with an aortic dissection and history of cocaine abuse.

PMID- 7630052
TI  - Decreasing "door to thrombolysis" time at one busy acute care hospital.

PMID- 7630053
TI  - Replacement of nurses with unlicensed assistive personnel: the erosion of
      professional nursing and what we can do.

PMID- 7630054
TI  - Oncologic emergencies: assessment, identification, and interventions in the
      emergency department.

PMID- 7630055
TI  - Ethical decision making in the emergency department: the R.O.L.E. acronym for
      four areas of consideration.

PMID- 7630056
TI  - Introducing the cardiac rhythm interpretation tree.

PMID- 7630057
TI  - CEN review questions. Thyroid storm.

PMID- 7630058
TI  - Sotalol: what the emergency nurse needs to know.

PMID- 7630059
TI  - Principles of EMS documentation for mobile intensive care nurses.

PMID- 7630060
TI  - New program start-up: gaining approval for your program and selecting your
      aircraft operator.

PMID- 7630061
TI  - Trauma nursing flow sheet.

PMID- 7630062
TI  - Providing a limited supply of medications for patients discharged from the
      emergency department.

PMID- 7630063
TI  - Creation of a "flex care" area in a busy emergency department.

PMID- 7630064
TI  - Toward a common language: Emergency Nursing Uniform Data Set (ENUDS).

PMID- 7630065
TI  - Pepper spray for emergency nurses: a hot topic.

PMID- 7630066
TI  - Getting through the IRB: Covenant Medical Center Nursing Research Committee's
      experience.

PMID- 7630067
TI  - On "high-heel brigades" and stopping civil wars.

PMID- 7630068
TI  - A 17-year-old female patient with seizures.

PMID- 7630069
TI  - A profile of emergency nursing.

PMID- 7630070
TI  - We did everything we could.

PMID- 7630071
TI  - ED patient and visitors' guide.

PMID- 7630072
TI  - [A clinical experience of DNA probe method for identifying Mycobacterium avium
      and Mycobacterium intracellulare].
AB  - In Japan the number of patient infected with M. avium complex (MAC) has been
      increasing in contrast to a decrease of pulmonary tuberculosis. DNA probe method
      enabled us be able to differentiate an isolated MAC into M. avium and M.
      intracellulare. From 1991 to 1992, we performed an investigation to apply this
      new technique of the DNA probe method on 52 patients of atypical mycobacteriosis
      diagnosed as infected with MAC by the ordinary method at the Higashi Nagoya
      National Hospital. The group consisted of 27 males and 25 females. M. avium
      infection was found in 39 patients (M. avium group) and M. intracellulare in 16
      patients (M. intracellulare group). No significant gender difference was found
      between two groups. The M. avium group showed more complications in contrast to
      the M. intracellulare group. As complications in the M. avium group, pulmonary
      aspergillus infection, bacterial pneumonia and bronchiectasis were found in 4, 3
      and 2 cases, respectively. The rate of drug resistance to antituberculosis drugs
      was high in the both groups. Chemotherapy with isoniazid (INH) rifampin (RFP) and
      streptomycin (SM) in five patients, that with INH, RFP and ethambutol (EB) in
      three were found to be effective after 4 months treatment. Three patients in M.
      avium group died of respiratory failure, aspergillus infection and renal failure.
      In contrast the prognosis of patients in the M. intracellulare group seemed to be
      better as there was no fatal case. We conclude that DNA probe method is useful to
      differentiate between M. avium and M. intracellulare, and enable us to select
      more appropriate selection of the chemotherapy and to assess of the prognosis.

PMID- 7630074
TI  - [A case of pulmonary tuberculosis associated with tuberculous fistula of anus].
AB  - A 39-year old male visited the hospital complaining of perianal pain, swelling
      and redness. Under the diagnosis of an anal abscess, drainage was performed
      repeatedly. As the wound failed to heal and fistulae were detected, excision of
      entire tract was performed. On histopathological examination of the resected
      fistulae, caseous necrosis, Langhans giant cells, and epithelioid cell
      infiltration were found and diagnosed as anal tuberculosis. Chest X-ray showed
      cavitary lesion with infiltrative shadow in right upper lobe. Acid-fast bacilli
      were positive in sputum, and the diagnosis of pulmonary tuberculosis was
      confirmed. Anti-tuberculosis therapy was immediately started with good response
      to treatment. As tuberculosis of anal region is so rare recently and there is no
      characteristic clinical picture, it is very difficult to diagnose it pre
      operatively. In some cases such as ours, pulmonary or other tuberculosis is
      accompanied with anal tuberculosis. Therefore, accurate diagnosis of anal
      tuberculosis is needed to find other tuberculosis early. As anal tuberculosis is
      rarely diagnosed correctly before operation on the basis of the clinical picture,
      the histopathological examination of the excised fistula is mandatory for the
      correct diagnosis of anal tuberculosis.

PMID- 7630073
TI  - [A rapid susceptibility test of Mycobacterium tuberculosis using hybridization
      protection assay].
AB  - The conventional drug susceptibility tests of Mycobacterium tuberculosis are time
      consuming and usually require 2 to 4 weeks to obtain final results. In this
      study, we attempted to develop a novel method for rapid detection of drug
      resistant M. tuberculosis using hybridization protection assay (HPA). Clinically
      isolated strains of M. tuberculosis including seven isoniazid (INH) susceptible
      strains and six resistant strains were used. The organisms grown on Ogawa egg
      medium were inoculated into Middlebrook 7H9 broth and cultured at 37 degrees C
      for one week. Then, the inoculum of each strain was prepared as a tenfold
      dilution of bacterial suspension at McFarland No. 0.5. The inocula were mixed
      with INH solutions to yield final concentrations of 0.1 and 1.0 micrograms/ml,
      and the resulting bacterial suspensions with or without test drug were cultured
      on the swaying plate at 37 degrees C for up to 5 days. At intervals, 50
      microliters of each sample was withdrawn and subjected to the protocol of the HPA
      using acridinium-ester (AE) labeled DNA probe, and then the relative light unit
      (RLU) was read in a luminometer. In the case of the susceptible strains, a
      significant difference in the mode of increase in RLU ratio (% of RLU on day
      x/RLU on day 0) was observed between the INH-treated and drug-free control sets
      within three days of cultivation, while no such differences were seen in the case
      of the resistant strains.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7630076
TI  - [Ultrasonic diagnosis of pyloroduodenal stenosis].
AB  - The method and semeiotics of noninvasive ultrasonic diagnosis of pyloroduodenal
      stenosis are described. Seventy-six patients with duodenal ulcer and 13 patients
      with gastric ulcer were examined, and also 18 patients with gastric carcinoma and
      24 healthy individuals. The echographic picture of an empty stomach in
      compensated pyloroduodenal stenosis did not differ from that in healthy persons,
      though study of the motor-evacuation activity of the stomach revealed intensified
      peristalsis and increased gastric half-evacuation period. In subcompensated
      pyloroduodenal stenosis the stomach contained fluid and the period of half
      evacuation of its contents was sharply increased. All patients with decompensated
      pyloroduodenal stenosis had an increased volume of the stomach which contained
      much fluid and food remnants. Pyloric spasm was differentiated by means of the
      spasmolytics test. Patients with a marked periulcerous inflammatory infiltration
      must be kept under dynamic follow-up to evaluate the degree of the stenosis.
      Taking into consideration the peculiarity of the echographic picture of the
      pyloric part, the neoplastic character of the pyloroduodenal stenosis may be
      presumed with high precision.

PMID- 7630075
TI  - [Enteral tube feeding of patients after esophagoplasty].
AB  - A method for enteral catheter feeding is suggested. It was applied in 60 patients
      after esophagoplasty. The main group consisted of 23 females and 37 males aged
      from 18 to 68 years. Esophageal carcinoma was observed in 31, burn stricture of
      the esophagus 18, and other benign diseases of the esophagus in 11 cases. All
      patients were subjected to extirpation of the esophagus with one-stage
      posteromedial esophagoplasty in 57 patients with an isoperistaltic gastric tube
      and in 3 patients with the colon. The control group was formed of 20 patients who
      underwent the same operations. Inpitan, ovolact, and hypernutril were used for
      enteral catheter feeding. The catheter was introduced via the nasal passage and
      transplant into the proximal segment of the jejunum. The mixtures were
      administered in drops of 5 to 7 days after the operation. Only parenteral feeding
      was conducted in the control group. The disorders of the alimentary status were
      removed quicker in patients of the main group than in the control and the
      incidence of postoperative complications was less. Body weight and the nitrogen
      balance were restored within a shorter time in the main group patients and
      incompetence of the esophageal anastomoses developed in a lesser number of cases.

PMID- 7630077
TI  - [Evaluation of abdominal treatment with magnetite suspension in peritonitis].
AB  - The work discusses the results of the effect of intraoperative treatment of the
      abdominal cavity with a magnetite suspension on the T-cell link of the
      immunological reactivity of the organism of patients with diffuse forms of
      peritonitis. The preparation intensified lymphocyte proliferative activity. It
      was found that increase of the lymphocyte stimulation index in intraoperative
      treatment of the abdominal cavity with magnetite suspension in peritonitis was
      consequent upon increased production of interleukin-1 and other growth factors by
      macrophages.

PMID- 7630078
TI  - [pT1 cancer of the rectum and sigmoid without signs of adenomatous background].
AB  - On the basis of analysis of the histological structure of 1,095 polypoid and
      nonpolypoid tumors, the frequency of detection of "primary" carcinoma and its
      clinical and histological features were studied. It is shown that one third of
      pTI category carcinomas are devoid of signs of a preceding adenoma. Polypoid
      primary carcinomas account for only 15.8% of cases. The prevailing plaque-like,
      flat, and ulcerated tumors invade the submucous layer more frequently than
      malignancy adenomas of the corresponding size and produce metastases to the lymph
      nodes more frequently. The tumor develops against the background of precancerous
      and dysplastic changes in the epithelium in the nonpolypoid mucosa and in the
      adenomas. The indications for economical operations in primary carcinoma, in
      distinct from those in malignancy adenomas, should be determined with caution.

PMID- 7630079
TI  - [Dyslipoproteinemia in pancreonecrosis: cause-effect interrelationships].
AB  - The work analyzes the results of study of lipid metabolism in 53 patients who
      underwent operation for pancreatogenic peritonitis. The blood for the test was
      collected from the portal vein, the hepatic vein, and the aorta which made it
      possible to appraise metabolism in the liver according to the "entry-exit" blood
      flow system. It is shown that due to pancreatogenic toxemia, toxemic hepatocytic
      dyslipoproteinemia develops in patients with pancreonecrosis and persists in the
      late period. As a consequence of such a condition of lipid metabolism, early
      atherosclerotic damages to the arteries of the heart and brain and the peripheral
      arteries occur in patients after pancreonecrosis. The fate of patients was
      studied 8-10 years after the operation. The nature of atherosclerotic
      manifestations of toxemic hepatocytic dyslipoproteinemia in the late period after
      recovery from destructive pancreatitis was determined on the basis of study of
      central and peripheral hemodynamics.

PMID- 7630080
TI  - [Ways of improving results of gastro-pancreatoduodenal resection in tumors of the
      bilio-pancreatoduodenal area].
AB  - The results of treatment of 86 patients who had been subjected to gastro
      pancreatoduodenal resection in the period from 1975 to 1992 were studied. The
      patients were divided into two groups. The main cause of postoperative mortality
      in the first group was the development of pancreonecrosis and incompetence of the
      pancreatico-enteral anastomosis. Hypothermia of the pancreatic duct and
      introduction of 5-fluorouracil into the pancreatic duct reduced postoperative
      mortality among patients of the second group from 34.9% to 13.9%. It is shown
      that this method may be applied in wide surgical practice.

PMID- 7630082
TI  - [The journal Khirurgiia is 70 years old].

PMID- 7630081
TI  - [Dynamics of the liver volume after its resection].
AB  - The dynamics of changes in the size of the liver after for localized lesions was
      studied in 42 patients. Both in benign and in malignant tumors the preoperative
      period was marked by compensatory hypertrophy of the lobes which were not
      involved in the tumor, and restoration of the size of the healthy hepatic
      parenchyma. In a period of up to 3 weeks after resection, sharp "blasting"
      enlargement of the remaining liver was noted due to increased filling with blood
      and edema of the organ. In the following periods up to 6 months, and sometimes of
      up to 12 months, the remaining part of the liver becomes smaller gradually to the
      preoperative size of the healthy parenchyma. The dynamics of the size of the
      liver after resection depends not on the character of the localized affection of
      the liver but on the volume of resection of the uninvolved parenchyma and the
      presence of concomitant diffuse changes in it.

PMID- 7630083
TI  - [Surgery in longevity].
AB  - The author treated and successfully operated on 8 patients aged 90 to 100 years,
      all the operations being made on abdominal organs from cholecystectomy to
      hemicolectomy. Such operations are possible and tolerable by some long-livers who
      frequently preserve adequate physical and mental activity.

PMID- 7630084
TI  - [Thin-needle aspiration biopsy of solitary formations of the thyroid gland].
AB  - The paper analyzes the use of thin-needle aspiration biopsy in 372 patients with
      thyroid solitary formations. By the results of clinical and instrumental studies
      and cytological examination of thyroid puncture specimens groups of patients with
      individual clinical and morphological types of the disease were identified.
      Differential surgical policy in each group of patients was shown on the basis of
      the finding. It is concluded that thin-needle aspiration biopsy should be
      integrated into the compulsory programme of comprehensive examination of patients
      with thyroid solitary formations. Having a high efficiency, the above method
      helps in most cases to make an accurate clinical and morphological diagnosis and
      to choose the optimal treatment policy for each specific patient admitted to a
      surgical hospital for an aggregate diagnosis of nodal euthyroid goiter. Some
      patients may avoid unjustifiable surgical intervention and be on conservative
      therapy under follow-up.

PMID- 7630085
TI  - [Organization of emergency aid to persons with injuries of the major blood
      vessels].
AB  - Emergency aid given to 1,258 persons with injury to the blood vessels is
      analysed. A new classification and 4 independent stages of emergency service are
      distinguished. An attempt is made to find common principles of organization of
      aid in time of peace and in time of war. The tactics in a combined vascular-nerve
      injury are substantiated, the indications for a tourniquet (18.3%) and temporary
      prostheses (16.9%) are suggested for reducing the incidence of postoperative
      complications, amputations, and mortality. The results of treatment (%):
      amputations, at the place of the accident 6.2, in the center 4.4, mortality 9.6
      and 2.2, respectively. The percentage of purulent complications was similar--6.6.

PMID- 7630086
TI  - [Neurologic disorders in patients with Madelung's lipomatosis].
AB  - The authors had 21 patients with a rare disease, Madelung's lipomatosis.
      Vegetative disorders of segmental and suprasegmental levels were revealed in all
      patients. The character of neuropathies in Madelung's lipomatosis is discussed in
      detail. According to the authors, it is a complex syndrome with peripheral,
      vegetative, and vascular disorders. The accompanying secondary scalenus syndrome
      produces a peculiar clinical picture of neuropathy. The existence of neurological
      disorders dictates the need for complex (surgical and medicamentous) treatment of
      patients with Madelung's lipomatosis.

PMID- 7630087
TI  - [Treatment of mediastinitis].
AB  - The authors work is based on experience in the study of 56 patients with acute
      mediastinitis of various origin who were treated in the period from 1981 to 1990.
      There were 33 males and 23 females whose ages ranged from 16 to 65 years,
      Odontogenous mediastinitis was diagnosed in 23, tonsillogenous in 2, and
      mediastinitis resulting from injury to the esophagus in 31 patients. Instrumental
      injuries prevailed. All patients underwent operation. The character of the
      operation was determined by the duration, localization, and severity of the
      pyonecrotic process in the mediastinum. Diffuse anterior mediastinitis was
      managed by tunneling and drainage of the mediastinum through the seat of the
      removed xiphoid process. Prophylactic treatment of the mediastinal space and
      intensive therapy including active detoxification were applied in the 56 patients
      who underwent operation died, 26 of them were admitted to the clinic 24-72 hours
      after the onset of the disease in a state of severe intoxication caused by
      violently developing mediastinitis. The remaining 27 patients recovered.

PMID- 7630088
TI  - [Surgical treatment of severe postburn flexion contractures of the hand].
AB  - The authors discuss the surgical tactics in multiple burn contractures of the
      palmar surface of the hand from experience in the treatment of 45 patients. The
      operation is conducted in one stage, with the manipulations performed in a
      definite order, which makes it much easier. The operation consists in correction
      of adduction of the thumb and the region of flexion contractures of the
      metacarpophalangeal articulations, palmar syndactyly, flexion contractures of the
      fingers, and contractions of the palm. Plastics with trapeziform grafts in
      combination of the palm. Plastics with trapeziform grafts in combination with
      free skin grafting makes it possible to correct all contractures in one stage and
      restore the function of the hand.

PMID- 7630089
TI  - [Use of antegrade endolymphatic administration of antistaphylococcal and
      antipseudomonal plasma in the treatment of infectious complications in severe
      multiple trauma].
AB  - The article deals with the treatment of infectious complications in persons with
      severe concurrent trauma. Microbiological study of the wound discharge and
      damaged tissues showed staphylococci and blue pus bacillus to be the principal
      causative agents of infectious complications. In view of the poor response of the
      immune system to the opportunistic flora, the performance of passive immunization
      with antistaphylococcal and antipseudomonal plasma is pathogenetically grounded.
      Taking into account the involvement of the lymphatic system in the infectious
      process, endolymphatic administration of the immune plasma is suggested.

PMID- 7630090
TI  - [Choice of the vagotomy method. The discussion is not finished].

PMID- 7630091
TI  - [Surgical and conservative treatment of uncomplicated duodenal ulcer].

PMID- 7630092
TI  - [Choice of surgical method in stomach ulcer].

PMID- 7630093
TI  - [Surgical policy in emergency proctology].
AB  - The article deals with 6-year experience of a department of emergency proctology
      accommodating 65 patients. Introduction into clinical practice of modern
      therapeutic tactics, highly effective medicaments, and top-duality
      anesthesiological service made it possible to cure radically 84.6% of patients
      with acute paraproctitis and 82.1% of those with acute hemorrhoidal thrombosis.
      Postponed radical operations are of undeniable advantage in the management of
      such patients. As a result of them complication incidence reduced from 10.7 to
      2.2% in acute paraproctitis and from 39 to 6.1% in acute hemorrhoids. In this
      connection the achievement of the best end results seems logical--the absence of
      recurrences in surgical treatment of acute suppuration of an epithelial coccygeal
      passage and acute thrombosis of the hemorrhoids, and a low incidence of
      recurrences (1.8%) after operations for acute paraproctitis.

PMID- 7630094
TI  - [Case cost flat rates discussed. The large hospitals are closing].

PMID- 7630095
TI  - [Nursing in the white sari].

PMID- 7630096
TI  - [Search for coping strategies. How to cope with stressful situations?].

PMID- 7630097
TI  - [Value instead of valium].

PMID- 7630098
TI  - [Nutrition behavior of the young. Tell me what you are eating...].

PMID- 7630099
TI  - [What kind of representation for our profession?].

PMID- 7630100
TI  - [A different way of care. Not necessarily an utopia].

PMID- 7630101
TI  - [The successful attempt to overcome anxiety and insecurity towards AIDS patients.
      How I turned into a reliable companion].

PMID- 7630103
TI  - [Women and men talking to each other in the work place. Misunderstandings among
      female colleagues].

PMID- 7630102
TI  - [Teaching midwives and their situation in the hospital environment. For a better
      quality of education].

PMID- 7630104
TI  - Alzheimer's disease in South Carolina, 1994.

PMID- 7630105
TI  - Nutritional screening of older South Carolinians: a pilot study.
AB  - Malnutrition can be a major health care problem for older adults. Thirty-one
      percent of the participants in a pilot study, conducted in Newberry county, were
      determined to be at high risk for nutritional deficiencies and 26 percent were at
      moderate risk. All health care professionals who work with the elderly must
      become aware of the NSI and offer the Checklist to their clients. The solutions
      to malnutrition require multidisciplinary interventions and the physician is the
      central figure in this team approach to improving the quality and quantity of
      life for older adults.

PMID- 7630106
TI  - Nocturnal blood pressure measurement: can it be predicted by self-monitoring and
      is 24-hr BP monitoring clinically important in the treatment of hypertension.
AB  - We predict that 24-hour blood pressure data will be required prior to starting
      treatment in order to receive third-party payment. We are currently performing a
      cost benefit analysis in patients with mild to moderate hypertension to see the
      prevalence of inappropriate treatment of hypertension (diagnosed by normal 24
      hour BP results) in an outpatient clinic population. We will compare the cost of
      treating that segment of the population that is inappropriately on treatment to
      the cost of 24-hour BP monitoring for the entire study population. As a result of
      this type of analysis, health care payors may require 24-hour BP documentation
      prior to hypertension treatment for all cases of mild to moderate hypertension.

PMID- 7630108
TI  - Principle-centered change.

PMID- 7630107
TI  - The response of South Carolina physicians to the demands of World War II.

PMID- 7630109
TI  - Adolescent varicocele: careful examination considerations.

PMID- 7630110
TI  - Mast cell modulation of macrophage procoagulant activity and TNF production.
AB  - The expression of surface procoagulants by macrophages represents an important
      mechanism underlying local fibrin deposition at sites of extravascular
      inflammation. Mast cells by virtue of their perivascular location are in a potent
      position to influence the inflammatory process. The present studies investigated
      the role of the mast cell in the generation of macrophage procoagulant activity
      (PCA) and tumor necrosis factor (TNF) production. Mast cell lysates caused a
      marked induction of macrophage PCA (dose and time dependent) and TNF release
      while whole mast cells had little effect. This effect was prevented by the
      tyrosine kinase inhibitor herbimycin. At the molecular level, Northern blot
      analysis revealed marked induction of the murine macrophage tissue factor
      transcript in response to incubation with mast cell lysate compared to control.
      These studies thus suggest that mast cell-macrophage interactions promote
      macrophage-mediated fibrin deposition and TNF release and that this effect is in
      part mediated via induction of tyrosine phosphorylation. These observations
      suggest novel mechanisms of involvement of the mast cell in the inflammatory
      microenvironment and macrophage activation.

PMID- 7630111
TI  - Tumor necrosis factor-alpha and interferon-gamma modulation of nitric oxide and
      allograft survival.
AB  - Tumor necrosis factor-alpha (TNF) and interferon-gamma (IFN) modulate immune
      responses, as TNF is postulated as a first messenger for priming immune cells and
      IFN as the second messenger for activation. Nitric oxide (NO) is also an
      important mediator of immune function, as NO produced by immune cells in response
      to cytokines such as TNF and IFN may be a cytotoxic end-product effector of
      immune activation. To examine TNF and IFN modulation of NO production and effects
      upon allograft survival, we studied the in vitro effect of TNF, IFN, and
      lipopolysaccharide (LPS, as a nonspecific immune stimulator and TNF promoter)
      singly or together on NO production in unstimulated rat splenocytes or in
      response to allogeneic stimulation in MHC mismatch (Brown-Norway, BN, vs Lewis,
      LEW) mixed lymphocyte reactions. Nitrite as a stable reaction product of NO was
      determined by a colorimetric method based on the Griess reaction. Interestingly,
      unstimulated cells had little NO production in response to TNF or IFN; however,
      following nonspecific (LPS) or allogeneic stimulation there was a significant
      upregulation of NO production that was synergistically enhanced by the presence
      of both TNF and IFN. Significantly, anti-TNF antibody inhibited NO production up
      to 60% in all groups. In vivo studies used a cardiac heterotopic allotransplant
      model, again BN to LEW. Control recipients received no immunotherapy.
      Experimental recipients received IFN alone, anti-IFN antibody, anti-TNF antibody,
      or anti-TNF and anti-IFN antibody. Results from these allograft experiments
      showed no influence on survival by IFN alone or anti-IFN antibody alone.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7630112
TI  - Cardiac preconditioning protects against irreversible injury rather than
      attenuating stunning.
AB  - The purpose of this experiment was to determine if cardiac preconditioning (PC)
      mediates protection by attenuating stunning or preventing irreversible injury.
      Inherent in the definition of myocardial stunning is the ability to respond to
      catechol stimulation after ischemia/reperfusion (I/R). Irreversibly injured
      myocardium cannot respond to catechols. We hypothesized that alpha 1-adrenergic
      stimulated PC is mediated through a functional protection against reversible
      injury. We investigated this hypothesis in the isolated, buffer-perfused rat
      heart subjected to global ischemia (20 min, 37.5 degrees C) and reperfusion (40
      min). The PC group received an alpha 1-adrenergic stimulus (norepinephrine, 0.5
      1.0 microM, 2 min) 10 min prior to ischemia. Control hearts were perfused
      normoxically for 80 min. Developed pressure (DP) and heart rate were recorded
      continuously. To determine maximal myocellular function, all hearts received a
      beta-adrenergic pathway stimulus (forskolin (FSK), 100 microM bolus) at end
      reperfusion. The ability to improve DP in response to FSK was indicative of
      reversible dysfunction (stunning). Failure to attain the maximal DP established
      in normoxic controls was utilized as a measure of irreversible dysfunction.
      Recovery was assessed as a percentage of initial DP. The results suggest that (1)
      PC protects against an I/R injury (recovery: I/R, 50.1%; PC + I/R, 76.0%; P <
      0.05); (2) all groups exhibit reversible dysfunction (all increased DP in
      response to FSK); (3) when maximally stimulated, I/R hearts are unable to develop
      pressures similar to those of normoxic controls, suggesting irreversible injury;
      and (4) PC hearts, however, attained similar maximal pressures compared to
      controls. We conclude that alpha 1-adrenergic PC improves postischemic cardiac
      function by preventing irreversible injury.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7630114
TI  - Specific modulation of intestinal epithelial brush border enzyme expression by a
      phorbol ester.
AB  - Much is known about intestinal epithelial regulation by growth factors and
      nutrients but the intracellular signals governing cell phenotype are less well
      understood. In an initial attempt to evaluate the role of protein kinase C in
      these events, we studied the effects of protein kinase C modulation by the
      phorbol ester TPA upon the differentiation, motility, and doubling time of the
      human intestinal epithelial Caco-2 cell line, a common model for enterocytic
      brush border enzyme expression. We also compared the effects of TPA to those of 4
      alpha-phorbol 12,13-didecanoate, which does not modulate protein kinase C
      activity. Differentiation was studied by quantitating brush order dipeptidyl
      peptidase (DPDD)-specific activity in protein-matched Caco-2 lysates via
      synthetic substrate digestion. Alkaline phosphatase (AP) was studied for
      comparison. Doubling time was assessed by log transformation of serial cell
      counts and motility by monolayer expansion across type I collagen. TPA (0.03-0.7
      micrograms/ml) dose-dependently stimulated DPDD, with a maximal 455 +/- 26%
      increase at 0.7 micrograms/ml (P < 0.01, n = 5). However, TPA dose-dependently
      inhibited AP to a maximal 91.6 +/- 0.3% decrease (P < 0.01, n = 5). TPA also dose
      dependently prolonged the cell doubling time from 26.5 +/- 0.4 to 64.5 +/- 8.8 hr
      (n = 20, P < 0.01) with a maximal effect at 1.0 micrograms/ml and inhibited
      migration with essentially complete ablation of cell motility at 0.1
      micrograms/ml (n = 10, P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7630113
TI  - Differential cloning of novel intestine-specific genes whose expression is
      altered under conditions of villus atrophy.
AB  - Atrophy of the small intestinal villi occurs in a variety of disease states and
      is associated with diarrhea, malabsorption, and impaired barrier function. We
      have previously demonstrated that villus atrophy is associated with an increase
      in lactase and a decrease in intestinal alkaline phosphatase gene expression.
      Given these changes in enterocyte phenotype with villus atrophy, we speculated
      that there may be other intestine-specific genes whose expression is altered as a
      function of epithelial growth state. We have employed two molecular techniques in
      order to identify and clone complementary DNAs (cDNA) which are differentially
      expressed in atrophic compared to normal small intestinal mucosa. In differential
      cDNA library (+/-) screening, duplicate filters of a normal jejunal cDNA library
      are hybridized with radiolabeled cDNA probes from either atrophic or control
      tissues. Comparisons of the intensities of hybridized clones allows for the
      identification of differentially expressed gene products. In the mRNA
      differential display system, RT-PCR is used to randomly amplify mRNA species.
      Similar to cDNA library screening, comparisons of radiolabeled bands on a
      polyacrylamide sequencing gel allow for the identification of differentially
      expressed genes. Using these methods, we have identified a novel cDNA, called D9,
      which appears to be expressed exclusively in the intestinal mucosa. Northern
      analyses have confirmed that the expression of the D9 mRNA is dramatically
      decreased under conditions of villus atrophy, suggesting an underlying
      relationship with epithelial growth state. DNA sequence analysis (GenBank)
      reveals no identity to previously cloned genes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7630115
TI  - Hepatocyte growth factor induces gastric H+/K(+)-ATPase expression.
AB  - The processes regulating the development of the fetal gastrointestinal tract are
      largely unknown, but are likely dependent, in part, on peptide growth factors.
      The purpose of this study was to determine the contribution of hepatocyte growth
      factor (HGF) to the development of the fetal gastric epithelium, with particular
      reference to the parietal cell. Fifty-six fetal rabbits from 18 time-mated
      pregnant New Zealand White rabbit does were divided into four groups at Day 23 of
      gestation (term is 31 days): (1) unoperated control littermates, (2) those
      prevented from swallowing amniotic fluid by esophageal ligation (EL), (3) those
      with EL plus intragastric carrier infusion, and (4) those with EL plus
      intragastric HGF infusion. At Day 28 of gestation, fetal stomachs were harvested
      and analyzed for gastric weight, DNA content, and H+/K(+)-ATPase expression. In
      control fetuses, gastric weight was 470 +/- 30 mg, gastric DNA content was 741 +/
      59 micrograms, and gastric H+/K(+)-ATPase expression was 25.4 +/- 2.7
      micrograms. EL resulted in a 45% decrease in gastric weight (P = 0.001), a 34%
      decrease in DNA content (P = 0.04), and a 43% decrease in H+/K(+)-ATPase
      expression (P = 0.007). These inhibitory effects were not reversed by
      intragastric carrier infusion. Although intragastric HGF infusion did not
      significantly restore gastric weight or gastric DNA content, it restored gastric
      H+/K(+)-ATPase expression to levels no different from those of unoperated
      controls (23.9 +/- 2.8 micrograms), but significantly greater than those of the
      EL or carrier infusion groups (P = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7630116
TI  - Hypoxia/reoxygenation affects endotoxin tolerance.
AB  - Pretreatment of animals with sublethal doses of endotoxin renders them tolerant
      to subsequent endotoxin challenge. Tissue hypoxia following infection may
      potentiate the immune response to injury. To evaluate the effect of
      hypoxia/reoxygenation (H/R) on endotoxin tolerance by macrophages, adult CBA mice
      were pretreated with 10 micrograms/animal of LPS injected intraperitonealy. Five
      days later, animals were subjected to 16 hr of hypoxia followed by 2 hr of
      reoxygenation. Harvested peritoneal macrophages were cultured and either
      stimulated in vitro with LPS or left unstimulated. Culture supernatants collected
      at 2, 4, and 6 hr were assayed for tumor necrosis factor (TNF), prostaglandin E2
      (PGE2), and nitric oxide (NO). Control animals underwent the same procedures, but
      were maintained in normoxia. H/R resulted in significantly greater TNF production
      but significantly lower PGE2 and NO production, P < 0.05 by ANOVA. These data
      suggest that LPS-induced tolerance of macrophages to the same stimulus is abated
      by H/R.

PMID- 7630117
TI  - Upregulation of angiotensin II type 1 receptor gene expression in chronic
      renovascular hypertension.
AB  - Although the renin-angiotensin system has been implicated in the pathogenesis of
      renovascular hypertension (RVH), blood pressure does not parallel serum levels of
      renin or angiotensin II (AII) in chronic RVH. Upregulation of angiotensin II type
      1 receptor (AT1) gene expression may explain this paradox and clarify the
      pathogenesis of chronic hypertension in RVH. To investigate this hypothesis, we
      studied changes in AT1 mRNA levels in rat kidney in a two-kidney, one-clip (2K1C)
      rat model of RVH. Animals were sacrificed at 1 or 10 weeks postoperatively. Blood
      pressure was measured with a tail cuff photosensor. Relative gene expression was
      quantitated by dot blotting total RNA, hybridizing with a cDNA probe for AT1, and
      quantitating signal intensity with scanning densitometry. A significant increase
      in blood pressure (BP) was observed at 1 week postoperatively (delta BP: 2K1C =
      +24 mm Hg, n = 3; controls = +7 mm Hg, n = 3; P < 0.05), and at this time
      relative AT1 mRNA levels actually decreased in the clipped kidney (P < 0.05).
      Hypertension intensified 10 weeks postoperatively (delta BP: 2K1C = +46 mm Hg, n
      = 20; controls = -17 mm Hg, n = 7; P < 0.005) and, remarkably, was paralleled by
      an almost sevenfold upregulation of AT1 mRNA levels in the clipped kidney (P <
      0.005) and more than eightfold in the unclipped kidney (P < 0.005) of 2K1C
      animals. Upregulation of renal AT1 gene expression could lead to increased AT1
      receptor production, hypersensitivity to AII, and chronic hypertension in RVH.

PMID- 7630118
TI  - Hypoxia-induced alterations of neutrophil membrane receptors.
AB  - Extravasation of leukocytes at sites of ischemia may mediate tissue injury. To
      determine how leukocyte accumulation may be induced by ischemia, effects of
      hypoxia on basal neutrophil expression of adhesion and activation receptors were
      examined. Effects of hypoxia upon preactivated cells were also studied. To
      determine whether regulation of expression is dependent on oxygen availability or
      on mitochondrial respiration, the effects of physical hypoxia (substitution of O2
      by nitrogen) were compared with those of chemical hypoxia with sodium cyanide
      (NaCN). Leukocytes in whole blood (eight volunteers) were exposed either to
      hypoxia alone or to priming concentrations of lipopolysaccharide (LPS, 1
      microgram/ml) followed by chemical hypoxia (NaCN, 1 mM) or physical hypoxia (PO2
      of 1-10 torr) for various time intervals. Room air was controlled and hypoxic
      cells were labeled with fluorescent monoclonal antibodies to integrins CD18 and
      CD11b or to the 55-kDa TNF alpha cell surface receptor (TNFR). Receptor
      concentrations were measured by flow cytometry. Data were analyzed by
      ANOVA/Student's t test. Physical hypoxia increased expression of both CD11b and
      CD18 over time and augmented their LPS-induced up-regulation. Isolated chemical
      hypoxia did not change neutrophil expression of CD11b or CD18, but partially
      inhibited neutrophil CD11b and CD18 up-regulation by LPS. LPS-induced TNFR down
      regulation was not affected by physical hypoxia, which failed to alter TNFR
      expression in this model.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7630119
TI  - Hemorrhagic shock-induced alterations in circulating and bronchoalveolar
      macrophage nitric oxide production.
AB  - Local and systemic host immune functions are markedly altered after trauma.
      Activated macrophages (M phi) are the major effector cells of protective
      immunity, mediated in part by nitric oxide (NO). This study was undertaken to
      determine the effects of hemorrhage (HEM) on M phi cytotoxic function as measured
      by NO production. Male Sprague-Dawley 350- to 400-g rats were studied. Sham
      animals only had their carotid artery exposed and ligated. Hemorrhaged animals
      had carotid artery cannulation followed by HEM to SBP of 40 mmHg, sustained for
      45 min, followed by resuscitation with shed blood and crystalloid. Recovered
      animals were sacrificed (n = 5 each) at 6, 12, 24, and 72 hr after HEM; blood and
      alveolar M phi were then isolated and examined. A monolayer of adherent M phi was
      examined for NO production in resting state and after in vitro LPS stimulation.
      (1) HEM resulted in significantly reduced alveolar M phi yield at 12 and 24 hr.
      (2) HEM increased NO production by circulating M phi at 24 hr (P < 0.05), while
      alveolar M phi had significantly increased NO production at all time points after
      HEM (P < 0.05). (3) LPS stimulation significantly increased NO production in both
      circulating and alveolar M phi in sham animals and 6 hr after HEM but not at any
      other times. We therefore conclude that HEM causes early and prolonged activation
      of NO production by alveolar M phi and delayed and brief activation of
      circulating M phi. Alveolar and circulating M phi are unable to significantly
      increase NO production in response to LPS stimulation during the later phases of
      HEM.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7630120
TI  - PEG-BP-30 monotherapy attenuates the cytokine-mediated inflammatory cascade in
      baboon Escherichia coli septic shock.
AB  - Septic shock following gram-negative infection is a leading cause of mortality in
      critically ill patients, accounting for nearly 200,000 deaths a year. The
      exaggerated production of tumor necrosis factor-alpha (TNF alpha) is known to
      contribute to hemodynamic collapse and the hematological dyscrasia associated
      with gram-negative sepsis. Although previous studies have shown TNF alpha
      antibodies and TNF immunoadhesins to be effective in experimental gram-negative
      sepsis, we postulated that administration of a novel construct of two modified
      soluble p55 receptors linked to polyethylene glycol (PEG-BP-30) would also
      attenuate the hemodynamic and hematologic alterations to lethal Escherichia coli
      septic shock in non-human primates. Nine adult female and male baboons (Papio
      anubis), weighing 10-17 kg, were anesthetized and invasively monitored. The nine
      animals were randomized to receive either 0.2 mg/kg body wt PEG-BP-30 (n = 3),
      5.0 mg/kg body wt PEG-BP-30 (n = 3), or placebo (n = 3). One hour after
      pretreatment, animals were infused with 5-10 x 10(10) CFU/kg of live E. coli iv
      and vital signs were recorded for the next 8 hr. Arterial blood was drawn for
      baseline parameters and throughout the study to obtain total and differential
      white blood cell and platelet counts and cytokine levels (TNF alpha, IL-1 beta,
      IL-6, IL-8). E. coli bacteremic baboons receiving only placebo demonstrated a
      significant fall in mean blood pressure and leukopenia. Two of the three animals
      expired. In contrast, five of the six baboons receiving the PEG-BP-30 survived
      and these animals exhibited markedly attenuated declines in blood pressure and
      leukocyte numbers.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7630121
TI  - Rolipram and isoproterenol reverse platelet activating factor-induced increases
      in pulmonary microvascular permeability and vascular resistance.
AB  - Platelet activating factor (PAF) is an important mediator of pulmonary
      microvascular endothelial cell (PMVEC) injury in sepsis. Membrane receptors for
      PAF have been identified on PMVECs and mediate its actions at least in part by
      protein kinase C activation. Since rolipram, a family IV cyclic AMP
      phosphodiesterase inhibitor, and isoproterenol, an adenylate cyclase activator,
      both reverse ischemia-reperfusion-induced lung permeability, we studied the
      effects of these agents on PAF-induced pulmonary microvascular permeability. The
      isolated rat lung model was used in which lungs were ventilated and buffer
      perfused at constant flow while suspended from a force transducer to monitor lung
      weight along with arterial (P(a)) and venous (Pv) pressures. Control lungs (n =
      6) were infused with PAF (40 nmole/kg) via an arterial port and the capillary
      permeability coefficient (Kf,c) was determined at 0, 15, and 60 min. The
      remaining lungs were randomized for infusion with either rolipram (n = 4, 20
      mumole/kg) or isoproterenol (n = 4, 5 mumole/kg) via an arterial port 30 min
      after injury with PAF. In the rolipram- and isoproterenol-treated groups, the
      Kf,c was determined 15 and 60 min postinfusion with these agents. The control
      group showed significant elevation in the Kf,c and total pulmonary resistance
      (Rt). At 15 and 60 min, rolipram and isoproterenol reversed PAF injury as shown
      by the significant improvement in the Kf,c and Rt. These findings support the
      concept that increased cyclic AMP is an important mediator in the reversal of PAF
      increased PMVEC permeability and pulmonary resistance.

PMID- 7630123
TI  - Localization of aortic disease is associated with intrinsic differences in aortic
      structure.
AB  - PURPOSE: While localization of atherosclerosis and aneurysms to the infrarenal
      aorta has been attributed, in part, to hemodynamic factors, anatomic differences
      between the proximal and the distal aorta may also be important. Our purpose was
      to determine the changes in content and organization of major structural proteins
      (elastin and collagen) throughout the normal human aorta. METHODS: Biochemical
      analysis for desmosine-isodesmosine (elastin) and hydroxyproline (collagen)
      content was done by HPLC on complete 1-cm transverse rings removed from the
      ascending and descending thoracic aorta and abdominal supraceliac, suprarenal,
      and midinfrarenal aorta. Elastin and collagen content was normalized to lumenal
      surface area and compared by ANOVA: Light microscopy and optical micrometry were
      used to determine changes in intimal, medial, and adventitial thickness and
      number of elastin lamellae at each level. RESULTS: Both collagen/cm2 and
      elastin/cm2 decrease from the proximal to distal aorta. Collagen content did not
      differ among the three abdominal segments, but there was a 58% decrease in
      elastin between the suprarenal and the infrarenal aorta. The proportion of
      elastin and collagen does not differ throughout the aorta except in the
      infrarenal aorta where there is decreased elastin relative to collagen.
      CONCLUSION: Collagen and elastin in the distal aorta bear an increased load as
      compared to the proximal aorta. The infrarenal aorta differs biochemically and
      histologically from the remainder of the aorta. A decrease in infrarenal elastin
      without a corresponding decrease in collagen may effect the compliance and
      integrity of the distal aorta. These anatomic differences may be important in
      predisposing the infrarenal aorta to atherosclerosis and aneurysm formation.

PMID- 7630122
TI  - The duration of infection modifies mitochondrial oxidative capacity in rat
      skeletal muscle.
AB  - Sepsis increases phosphocreatine (PCr) breakdown and reduces PCr stores in
      skeletal muscle. To determine if systemic infection impairs mitochondrial
      function, in vivo 13P magnetic resonance spectroscopy (31P MRS) studies of the
      gastrocnemius muscle were performed in virus-free male Wistar rats 24 or 48 hr
      after cecal ligation and 18-gauge needle single puncture (24 degrees CLP, n = 16;
      48 degrees CLP, n = 15) or sham operation (24 degrees SHAM, n = 18; 48 degrees
      SHAM, n = 13). Physiologic saline (6 ml/100 g body wt) was injected
      intraperitoneally for fluid resuscitation. Water but no food was allowed in all
      animals. High resolution (8.45 Tesla) 31P MRS spectra, obtained at rest and
      during exercise using a 1.4-cm surface coil, were used to calculate PCr/ATP,
      PCr/P(i) ratios, and intracellular pH. Steady-state muscle exercise was induced
      by supramaximal sciatic nerve stimulation at 10 Hz for 10 min. Recovery of
      PCr/(PCr + P(i)) ratios after exercise was fitted to a monoexponential curve. The
      resultant function was used to calculate the half time for PCr recovery, the
      initial PCr resynthesis rate, and the maximal oxidative ATP synthesis rate, which
      reflect the rephosphorylation of ADP and are therefore measures of mitochondrial
      oxidative capacity. PCr/ATP ratios decreased by 12 and 11%, 24 and 48 hr after
      CLP, respectively. The PCr/P(i) ratios decreased incrementally (7% in 24 degrees
      CLP vs 23% in 48 degrees CLP animals). Twenty-four hours after operation the half
      time for PCr recovery was shortened while the initial PCr resynthesis rate and
      maximal oxidative ATP synthesis rate were accelerated in CLP animals compared to
      controls.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7630124
TI  - The mechanism of amino acid loading in improving postischemic myocardial
      recovery.
AB  - During induced ischemia for cardiac surgery, myocardial stunning occurs and
      aerobic metabolism of glucose, fatty acids, and lactate is altered. Following
      reperfusion, stunned myocardium uses oxygen and substrate inefficiently, leading
      to poor functional recovery. However, amino acids may be used as anaplerotic
      metabolic substrates during and after ischemia, utilizing transamination of amino
      acids to form high-energy phosphates via the tricarboxylic acid cycle. We
      investigated if loading hearts with a physiologic spectrum of amino acids prior
      to ischemia could increase postischemic myocardial recovery. Isolated perfused
      rabbit hearts were subjected to 120 min of 34 degrees C cardioplegic ischemia.
      Hearts received cardioplegia alone as controls or were loaded with a 0.05, 0.1,
      0.5, 1, 2, or 5% amino acid perfusion prior to cardioplegic ischemia. Following
      reperfusion, functional recovery revealed that hearts perfused with 0.05 and 0.1%
      amino acids had improved contractility and compliance vs untreated controls. To
      determine if the mechanism of amino acid loading in improving postischemic
      function was enhancement of high-energy phosphate resynthesis, nucleotides and
      nucleosides were measured. While all preischemic values were equivalent, amino
      acid-loaded hearts had significantly greater high energy nucleotides at end
      ischemia and after reperfusion. These data demonstrate that metabolism, as well
      as function, is improved with amino acid loading prior to ischemia, which allowed
      for better internal reparative work during ischemia and external contractile work
      after ischemia. This strategy may have application in cardiac surgery.

PMID- 7630125
TI  - Gel-entrapment bioartificial liver therapy in galactosamine hepatitis.
AB  - A need exists for an effective, safe bioartificial liver to support patients in
      fulminant hepatic failure (FHF). The purpose of this study was to determine the
      treatment efficacy of the novel gel-entrapment porcine hepatocyte bioartificial
      liver (BAL) in a fatal model of canine hepatic failure. FHF was produced in 27-
      to 30-kg halothane-anesthetized dogs by bolus infusion of the hepatotoxin D
      galactosamine (D-Gal). Three groups were studied during the 48-hr experiment:
      Group D-Gal (n = 5) received galactosamine, 1.0 g/kg, iv at Time O, Group HepBAL
      (n = 5) received D-Gal followed by continuous hemoperfusion with the BAL device
      loaded with approximately 6 billion viable pig hepatocytes starting at Time 24
      hr, and three dogs served as healthy controls (Group Control) and received no
      galactosamine. The primary endpoints were survival and coma development. Group D
      Gal demonstrated 100% mortality from liver failure by 42 hr, characterized by a
      progressive rise in liver enzymes, total bilirubin, ammonia, and lactate and
      associated with coagulopathy, hypoglycemia, coma, and brain death. BAL therapy
      significantly delayed the onset of coma and improved survival (median 47 hr vs D
      Gal median 36 hr). A significant delay in the rise of lactate and ammonia was
      also noted. BAL therapy prolonged survival and improved both laboratory and
      clinical markers of fatal liver failure. These data indicate that this BAL may
      have clinical utility in supporting human liver failure.

PMID- 7630126
TI  - Beta-adrenergic modulation of the collateral-dependent coronary microcirculation.
AB  - The effect of chronic, collateral-dependent perfusion on beta-adrenergic coronary
      microvascular responses was examined. Ameroid constrictors were placed on the
      proximal left circumflex (LCx) coronary artery in 16 pigs. In 8 pigs, heparinized
      saline containing vascular endothelial growth factor (VEGF) was administered into
      the perivascular space of the proximal LCx artery using an implanted osmotic
      pump. After 5-7 weeks, coronary arterial microvessels (70-150 microns) were
      studied in a pressurized (40 mm Hg) no-flow state with video-microscopy. beta
      Adrenoceptor-mediated relaxations of isolated microvessels from the collateral
      dependent LCx region to isoproterenol (P < 0.01) were markedly reduced, as were
      those to the adenylate cyclase activator forskolin (P < 0.01), compared to the
      respective response of vessels from the normally perfused left anterior
      descending artery region. Responses to the Gs-protein activator NaF showed a
      similar trend, but the differences were not significant. Chronic treatment with
      VEGF normalized responses to isoproterenol, NaF, and forskolin in the collateral
      dependent LCx region. Blood flow in the LCx region increased in both control (P <
      0.01) and VEGF-treated (P < 0.05) groups during rapid atrial pacing. The absolute
      increase in LCx blood flow was greater in the VEGF group than in the control
      group at rest (P < 0.05), but not during rapid pacing. Thus, beta-adrenergic
      microvascular relaxation is impaired in the collateral-dependent coronary
      microcirculation. The periadventitial delivery of VEGF improves myocardial
      perfusion to the collateral-dependent area and preserves beta-adrenergic-mediated
      relaxation of microvessels in the collateral-dependent myocardium.

PMID- 7630127
TI  - Morphometry and histochemistry of pulmonary arteries in a hypoplastic lung model.
AB  - Persistent pulmonary hypertension (PPH) is a common consequence of many neonatal
      respiratory diseases. The pathophysiology of PPH remains unknown. To study PPH, a
      rat model of pulmonary hypoplasia was used. Lung mass and body mass were recorded
      and lungs were prepared for frozen section examination and stained with
      hematoxylin and eosin, elastin, anti-Factor VIII, and nitro blue tetrazolium to
      identify nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase. The
      lungs were analyzed for air space volume, pulmonary artery wall thickness, total
      pulmonary arterial cross-sectional area, and density of tissue NADPH diaphorase
      staining. The mass of hypoplastic lungs was less than that of normal lungs (mean
      mass 85.93 mg vs 142.97 mg, P < 0.0001). The measured fraction of airspace volume
      was significantly less in hypoplastic lungs compared to controls (17.7% vs 30.8%,
      P < 0.0001). There was a significant difference in the pulmonary artery wall
      thickness ratio between the two groups (control 0.46 vs hypoplastic 0.487, P =
      0.001). The arterial cross-sectional area was identical (control 1.25% vs
      hypoplastic 1.37%, P = 0.47). Staining density for NADPH diaphorase activity was
      determined using an intensity staining index (ISI). The experimental group showed
      increased staining for NADPH diaphorase (ISI = 54 in hypoplastic lungs vs 38 in
      controls, P < 0.01). Lung mass, appearance, and measured volume of airspace and
      tissue were all consistent with hypoplasia. In this model, arterial wall
      thickness was measurably greater in the hypoplastic group, while arterial cross
      sectional area was not different. Staining for NADPH diaphorase showed
      significantly greater levels of enzyme in the hypoplastic lung.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7630128
TI  - The cumulative nature of pyruvate's dual mechanism for myocardial protection.
AB  - Pyruvate (PYR) supplementation protects myocardium from ischemia reperfusion
      injury. This study was designed to characterize and quantify the mechanism
      underlying this protection: specifically whether this ability resides in PYR's
      metabolic effect or in its antioxidant effect. Isolated perfused rat hearts (n =
      6/group) were subjected to 15 min of equilibration (EQ), 25 min of ischemia, and
      10 min of reperfusion (RP). Glucose was the sole metabolic substrate (Control) or
      was supplemented with PYR (5 mM) during (a) EQ only (PYREQ group), (b) RP only
      (PYRRP group), or (c) EQ and RP (PYREQ-RP group). Left ventricular developed
      pressure (DP) and +/- dP/dt were recorded throughout the experiment. ATP
      concentrations and intracellular pH were determined by 31P NMR spectroscopy.
      Myocardial creatinine kinase (CK) activity was assayed at end EQ and end RP. In
      vitro, purified CK was assayed and, after exposure to H2O2 (200 microM) and
      increasing concentrations of PYR (0-6 mM) for 10 min, reassayed to determine the
      antioxidant effect of PYR. In all cases PYR improved recovery of mechanical
      function at end RP (DP: Control, 11 +/- 1%; PRYRP, 23 +/- 6%; PYREQ, 34 +/- 8%;
      PRYEQ&RP, 53 +/- 7%; P < 0.05 between all groups and Control). Ischemic
      contracture was delayed in hearts that received PYR during EQ (PYREQ and
      PYREQ&RP: 17.8 +/- 0.2 vs 12.5 +/- 0.3 min, P < 0.001). PYR during EQ (PYREQ and
      PYREQ&RP) led to higher end ischemic ATP levels (32 +/- 4% vs 14 +/- 3%, P <
      0.001) and a more acidic end ischemic pH (5.92 +/- 0.02 vs 5.98 +/- 0.03 in
      Control and PYRRP, P < 0.05). PYREQ&RP showed the highest end reperfusion ATP
      levels (55 +/- 7% vs 38 +/- 4%, P < 0.05 vs other groups).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7630129
TI  - In situ expression of platelet-derived growth factor (PDGF-beta) during chronic
      rejection is abolished by retransplantation.
AB  - We have shown that Fischer 344-->Lewis renal allografts (ALLO) develop chronic
      rejection which is not detected in Lewis-->Lewis isografts (ISO). The progression
      of chronic rejection in ALLO can be reversed by retransplantation (RE-TX) of
      kidneys from ALLO back into syngeneic Fischer 344 recipients. The purpose of this
      study was to assess the in situ expression of PDGF-beta, a cytokine associated
      with wound injury, in ISO, ALLO, and RE-TX. In situ PDGF-beta mRNA expression in
      kidney sections was assessed early (8 weeks) and late (16 weeks) during the
      development of chronic rejection. Kidneys from ALLO were transplanted back into
      syngeneic Fischer recipients at 12 weeks and evaluated for PDGF-beta expression
      12 weeks later. Differences in glomerular staining were graded quantitatively on
      a minimum of 25 glomeruli per section with grade 0, no positive cells in the
      glomerulus; grade 1, 1 or 2 positive cells; grade 2, 3 or more positive cells in
      a segmental distribution; and grade 3, > 4 positive cells of moderate intensity
      in a diffuse distribution. According to this grading system, glomerular PDGF-beta
      mRNA expression in isografts (N = 6) at 8 and 16 weeks after transplantation was
      0.09 +/- 0.03 and 0.2 +/- 0.04, respectively. In allografts (N = 6), PDGF-beta
      mRNA was significantly higher (P < .001) for the same time periods, 1.28 +/- 0.6
      and 1.89 +/- 0.08, respectively. In situ expression of PDGF in retransplants (N =
      6) at 24 weeks, 0.07 +/- 0.02, was significantly diminished (P < .001) at 24
      weeks compared to allografts at 8 or 16 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7630130
TI  - A novel nonanticoagulant heparin improves splenocyte and peritoneal macrophage
      immune function after trauma-hemorrhage and resuscitation.
AB  - Recent studies have shown that heparinization of animals prior to or even after
      hemorrhagic shock improves tissue perfusion and organ function. However, the
      anticoagulant properties of conventional heparin preclude its clinical use in
      trauma care. The aim of our study, therefore, was to determine whether chemically
      modified heparin, i.e., a novel nonanticoagulant heparin (GM1892), which does not
      have significant anticoagulant activity (approximately 2% of the anticoagulant
      activity of conventional heparin), produces any beneficial effects on splenocyte
      and macrophage immune function following trauma-hemorrhage and resuscitation. To
      determine this, following the induction of tissue trauma (i.e., a midline
      laparotomy), mice were bled to and maintained at a mean arterial pressure of 35
      mm Hg for 1 hr. The animals then received GM1892 (7 mg/kg body wt), conventional
      heparin (7 mg/kg body wt), normal saline prior to resuscitation with three times
      the volume of shed blood with Ringer's lactate. Two hours after resuscitation the
      animals were sacrificed, splenocytes were isolated, and splenic, as well as
      peritoneal macrophage, cultures were established. The ability of the splenocytes
      to release IL-2 and IL-3 in response to mitogen was markedly improved in
      hemorrhaged animals which were treated with GM1892 or conventional heparin
      compared to saline-treated mice. Furthermore, the capacity of splenic and
      peritoneal macrophages to release IL-6 was restored in the hemorrhaged animals
      that received GM1892 or conventional heparin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7630131
TI  - Transduction of hepatic allografts achieves local levels of viral IL-10 which
      suppress alloreactivity in vitro.
AB  - The application of gene therapy in transplantation might be targeted at
      immunoregulation within the donor graft. Viral IL-10 (vIL-10) down-regulates
      antigen presenting cells (APC) and effector functions in in vitro and in vivo
      models of alloreactivity. In the current study, we have constructed a replication
      defective adenovirus bearing the cDNA encoding viral IL-10 and examined the level
      and chronicity of its expression in rat liver allografts up to 7 days after
      orthotopic transplantation. The results demonstrate that liver allografts may be
      efficiently transfected with adenovirus expressing viral IL-10. Detection of the
      recombinant viral cytokine was limited to the allograft without measurable levels
      in peripheral blood. In parallel, the effect of vIL-10 on mixed leukocyte
      reaction is also assessed using peripheral blood lymphocytes obtained from naive
      donor and recipient animals. Equivalent levels of viral IL-10 (5-10 ng/ml)
      achieved after adenovirus-mediated gene transfer suppress the in vitro
      alloreactivity of peripheral blood lymphocytes up to 70%. Adenovirus-mediated
      gene transfer of viral IL-10 offers the promise of effectively and favorably
      altering the alloreactive immune response.

PMID- 7630133
TI  - Regional blood flow redistribution in preterm piglets with hemorrhage and
      resuscitation.
AB  - Acute hemorrhage in premature infants occurs as the result of obstetrical
      complications, birth trauma, or operative procedures. This study evaluates the
      response of the preterm piglet to acute hemorrhage and resuscitation. Piglets
      delivered by Caesarean section 7-14 days preterm underwent acute arterial/venous
      hemorrhage (20 cc/kg). At 0, 15, and 60 min after hemorrhage, hemodynamic
      parameters and regional blood flows (reference organ technique) were measured.
      Animals were then resuscitated with shed blood (20 cc/kg), crystalloid (60
      cc/kg), or colloid (dextran 40, 20 cc/kg) with study parameters obtained 30 min
      later (statistical analysis by ANOVA). Significant decreases in blood pressure
      (BP) and cardiac output (CO) occurred after hemorrhage. BP and CO were
      reestablished to near control levels following resuscitation with blood and
      crystalloid. Dextran failed to return BP to baseline; however, it resulted in CO
      1.7 x control. Heart and CNS blood flow were not significantly influenced by
      hemorrhage; however, dextran increased flows to these organs significantly above
      control levels. In the kidney and small bowel, flows decreased significantly
      following hemorrhage; blood and crystalloid restored flows to near baseline,
      while dextran resulted in flows significantly greater. In summary, the preterm
      piglet responds to hemorrhage with maintenance of blood flow to the heart and
      brain and significantly decreased flows to the kidney and small intestine. Flows
      following resuscitation with blood and crystalloid are comparable to those in
      control. Dextran resuscitation resulted in flows significantly greater than
      baseline; this response might be detrimental with ongoing hemorrhage and/or
      prolonged ischemia.

PMID- 7630132
TI  - Parenteral nutrition alters monocyte TNF receptor activity.
AB  - The route of nutrient provision has been reported to influence some aspects of
      the host inflammatory response in both patient populations and normal subjects.
      The tumor necrosis factor receptor system is a complex regulatory mechanism that
      modulates the bioavailability of tumor necrosis factor (TNF). We sought to
      determine whether maintenance on total parenteral nutrition (TPN) can alter host
      response to endotoxin challenge, specifically as it relates to the TNF receptor
      system. Seventeen healthy men were randomized to receive either TPN (n = 8) or a
      defined formula enteral diet (ENT, n = 9) prior to intravenous infusion of
      endotoxin (Lot EC-5, 20 U/kg). The subjects that received 1 week of antecedent
      TPN exhibited an increased heart rate and temperature and decreased mean arterial
      pressure post-LPS compared to those subjects maintained on enteral nutritional
      support. The TPN subjects also exhibited comparatively higher TNF and interleukin
      6 levels in response to endotoxin. Monocyte TNF receptor levels decreased in both
      groups post-LPS, but TPN subjects exhibited consistently greater expression of
      this functional membrane-associated TNF receptor. After LPS, soluble tumor
      necrosis factor receptor II (sTNFr II, p75) peaked three times higher in TPN
      subjects than in ENT subjects. Conversely, sTNFr I (p55) was higher in the
      enterally fed group. From these studies it appears that antecedent TPN not only
      influences clinical manifestations of endotoxin but also modulates the regulation
      of all associated TNF receptors and shedding of soluble receptors.

PMID- 7630134
TI  - Control of accelerated vein graft atheroma with the nitric oxide precursor: L
      arginine.
AB  - Hyperlipidemia contributes to the development of intimal hyperplasia and
      subsequent accelerated atherosclerosis in vein bypass grafts. This study examines
      the effect of dietary supplementation with L-arginine on the development of
      intimal hyperplasia and the vasomotor function of vein grafts in
      hypercholesterolemic animals. Thirty male New Zealand White rabbits had a right
      carotid vein bypass graft and were sacrificed at 28 days postoperatively. Twenty
      animals received a 1% cholesterol diet for 4 weeks prior to surgery and this diet
      was continued until harvest. Of these, 10 also received L-arginine (2.25%, 2
      g/kg, p.o.) 7 days preoperatively and thereafter until harvest. The last 10
      animals were controls. Vein grafts were harvested either for morphology or for in
      vitro isometric tension studies. Cumulative dose-response curves to
      norepinephrine, serotonin, and bradykinin were recorded, and following
      norepinephrine precontraction, relaxation to acetylcholine and sodium
      nitroprusside were determined. After in situ pressure fixation, intimal
      thicknesses of the vein grafts were measured by videomorphometry. The addition of
      L-arginine doubled the serum arginine concentrations. Intimal hyperplasia of both
      groups of hypercholesterolemic vein grafts contained foam cells and lipid-laden
      endothelial and smooth muscle cells. There was a 24% reduction in the intimal
      thickness of vein graft intimal hyperplasia in the L-arginine group compared to
      that in the hypercholesterolemia group (P < 0.05). All hypercholesterolemic vein
      grafts were two-fold thicker than in the control group. L-arginine
      supplementation resulted in the preservation of acetylcholine-mediated relaxation
      but did not change hypercholesterolemia-induced contractile agonist
      supersensitivity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7630135
TI  - Antibody removal by column immunoabsorption prevents tissue injury in an ex vivo
      model of pig-to-human xenograft hyperacute rejection.
AB  - Hyperacute rejection of a pig-to-primate organ xenograft is triggered by binding
      of anti-pig endothelial cell antibodies to the vascular endothelium of the
      xenograft and complement activation. Xenograft survival can be prolonged by
      pretransplant depletion of antibody with plasmapheresis or organ perfusion.
      However, these techniques have disadvantages for use immediately pretransplant or
      in the post-transplant period, including a marked reduction in coagulation
      proteins. To remove IgM and IgG from human plasma we employed a reusable Ig
      binding column containing polyclonal anti-human IgG (heavy chain- and light chain
      specific) conjugated to Sepharose beads (Therasorb, Baxter Corp.). Human blood
      was separated into plasma and cell fractions. Column absorption of plasma
      followed by recombination of plasma and cell fractions in the perfusion system
      resulted in 90.5 and 86.0% reduction in total IgG and IgM, respectively, and in a
      47.0 and 69.4% reduction in IgG and IgM anti-pig endothelial cell antibodies,
      respectively. When the cellular fraction was recombined with untreated plasma and
      used to perfuse pig hearts in an ex vivo perfusion system, there was rapid
      cessation of normal cardiac rhythm (25.2 +/- 5.6 min) and intense deposition of
      Igs, complement proteins, and fibrin in the tissues. In contrast, perfusion with
      blood containing column-absorbed plasma was able to sustain cardiac function,
      with normal sinus rhythm maintained for 258 +/- 48.1 min, without tissue
      deposition of IgM or complement proteins and minimal deposition of IgG. We
      conclude that column absorption can be used effectively to deplete plasma of anti
      pig endothelial cell antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7630136
TI  - Pulmonary subpleural arteriolar diameters during intestinal ischemia/reperfusion.
AB  - Adult respiratory distress syndrome (ARDS) often occurs in response to sepsis,
      shock, or ischemia/reperfusion (I/R) of a remote organ and is a frequent cause of
      mortality in the ICU patient. Pulmonary vascular resistance (PVR) increases
      during ARDS, yet direct observations of the pulmonary microcirculation are needed
      to characterize the vascular response. The purpose of this study was to
      quantitate the changes in hemodynamic variables, subpleural arteriolar diameters
      (AD), and alveolar cross-sectional areas (ACSA) during intestinal I/R-induced
      lung injury in rats, using a new method of in vivo videomicroscopy. Sprague
      Dawley rats were anesthetized and cannulated, and superior mesenteric arteries
      were looped. A thoracotomy was performed with animals ventilated with air with 1
      cm PEEP. Hemodynamic and videomicroscopic data were obtained before and during 45
      min of SMA occlusion and after reperfusion, up to 120 min. Maximal vessel
      dilation was measured using topical 10(-5) M nitroprusside. The ability of
      vessels to constrict was confirmed by applying topical 10(-6) M endothelin-1.
      Intestinal I/R produced decreases in arterial pH, mean arterial pressure, and
      cardiac output. Despite these alterations, subpleural AD remained maximally
      dilated. Arterioles maintained the ability to constrict as demonstrated by the
      response to topical endothelin-1. ACSA did not change, indicating a uniform
      inflation of the lung. Using a unique method of in vivo pulmonary
      videomicroscopy, we have shown that AD do not change following 120 min of
      intestinal I/R, despite systemic hemodynamic instability. It appears that
      pulmonary arteriolar vasoconstriction does not contribute to increased PVR during
      the early phase of lung injury.

PMID- 7630137
TI  - Glucocorticoids regulate rat glutamine synthetase expression in a tissue-specific
      manner.
AB  - During stress states, organismal glutamine production is augmented secondary to
      an increase in the activity of glutamine synthetase (GS) in the lung and skeletal
      muscle. Because glucocorticoids are key regulators of the metabolic response to
      stress, we undertook a survey of glucocorticoid induction of GS expression in rat
      organs in response to dexamethasone. Male adult rats were injected with
      glucocorticoid or vehicle and 4 hr later, 10 organs were assayed for GS messenger
      RNA and protein contents by Northern and Western blotting. We observed a 20-fold
      range of GS mRNA levels in organs of control animals. Blotting detected two GS
      RNA species of approximately 2.8- and 1.4-kb sizes in all tissue except testis,
      where an additional 2-kb RNA species was observed. Glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH) mRNA levels were also assayed and used as a normalization
      factor. An approximately 10-fold range of GAPDH mRNA levels was observed. Four
      hours after dexamethasone injection, a nearly a 5-fold increase in glutamine
      synthetase mRNA levels in lung and muscle, as well as an approximately 2-fold
      increase in heart were observed. Relative to GAPDH mRNA, a significant decrease
      in GS mRNA levels was observed in the liver. A wide range of glutamine synthetase
      protein contents were observed in rat organs. Comparison of Northern and Western
      blotting results revealed a dichotomy in the ratio of relative GS mRNA and
      protein level in rat organs, suggesting that tissue-specific posttranscriptional
      processes determine GS protein levels.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7630138
TI  - Insulin-like growth factor-I (IGF-I) and glutamine improve structure and function
      in the small bowel allograft.
AB  - IGF-I, a mitogenic polypeptide hormone, and glutamine (GLN), the preferred
      enterocyte fuel, singularly improve growth and structure of the small bowel
      isograft; however, their combined effects on intestinal allografts are unknown.
      This study examined the effects of IGF-I and GLN, singularly and in combination,
      on the structure and function of the intestinal allograft. Fifty-nine adult rats
      underwent resection of the distal 60% of small bowel and received either a 40-cm
      isograft or an allograft. Either IGF-I (2.4 mg/kg/day) or its vehicle was infused
      continuously by subcutaneous minipumps. An isocaloric polymeric diet with either
      2% GLN or isonitrogenously balanced 2% nonessential amino acids was given
      continuously by gastrostomy for 10 days. Five groups were studied: isograft (ISO)
      alone, allograft (ALLO) alone, ALLO and GLN, ALLO and IGF-I, and ALLO and IGF-I
      with GLN. All recipients received Cyclosporine A (15 mg/kg, im) daily. Mucosal
      villus height, surface area, crypt depth, IgA, IgG, IgM, and intercellular
      adhesion molecule-1 (ICAM-1) plasma cells in intestinal tissue, glucose and water
      absorption of intestinal graft, bacterial translocation (BT) to mesenteric lymph
      nodes, and body weight were determined. IGF-I increased villus height, surface
      area (P < 0.001), crypt depth (P < 0.01), and glucose absorption (P < 0.05)
      compared to the ISO and ALLO groups. GLN increased only crypt depth when compared
      to the ALLO group (P < 0.01). Both IGF-I and GLN independently decreased BT to
      MLN (P < 0.05) and, in combination, enhanced water absorption (P <
      0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7630139
TI  - Enhanced expression of ICAM-1 in a murine fibrosarcoma reduces tumor growth rate.
AB  - Intercellular adhesion molecule-1 (ICAM-1) plays an essential role in lymphocyte
      adhesion to endothelium and migration across endothelial cell barriers. We
      undertook this study to determine the growth of a murine fibrosarcoma transfected
      with the ICAM-1 gene. MCA-105 tumor cells were cotransfected with ICAM-1 and the
      plasmid for neomycin resistance (NeoR). Selected G418-resistant clones were
      expanded and cell surface ICAM-1 expression was verified using a fluorescence
      activated cell sorter. Integration of the ICAM-1 gene and ICAM-1 mRNA expression
      were verified by Southern and Northern blot hybridization analysis, respectively.
      C57BL/6 mice were divided into five groups (six animals/group): Control, NeoR
      only, ICAM-1 (low expressing, Clone 25), ICAM-1 (high expressing, Clone 81), and
      a 1:1 mixture of NeoR:Clone 81; animals received 1 x 10(6) cells on Day 0 and
      tumor measurements began on Day 7 and were measured in mm2. At 19 days, tumors
      from cell lines expressing ICAM-1 were significantly (P < .05) smaller than both
      the parental cell line and tumor-containing NeoR only (364 mm2 vs 466 mm2 and 527
      mm2, respectively). This decrease in tumor growth may be a result of increased
      lymphocyte migration or increased anti-tumor cytotoxicity by infiltrating
      lymphocytes. The results from the mixed tumor experiment suggest a possible
      paracrine effect by cells expressing ICAM-1. Studies are currently under way to
      investigate the effect of immunotherapy on tumors derived from ICAM-1-cloned
      transfectants.

PMID- 7630140
TI  - Hemorrhagic shock abolishes the myelopoietic response to turpentine-induced soft
      tissue injury.
AB  - Hemorrhagic shock has been shown to alter bone marrow (BM) myelopoiesis. Isolated
      hemorrhagic shock is uncommon after trauma and the combined effect of tissue
      injury and shock on myelopoiesis is unknown. We studied the growth of BM
      granulocyte-macrophage colony forming units (CFU-GM) following shock and soft
      tissue injury. Rats were anesthetized and allocated into one of four groups:
      CONTROL, sham neck dissection; SHOCK, rats were bled to a mean BP of 45 mmHG for
      45 min and resuscitated with shed blood and saline; TURP, soft tissue injury was
      induced by turpentine 0.5 ml/100 g SQ into the hindquarter; SHOCK + TURP, rats
      received TURP just before SHOCK as described above. Groups (n = 6) were
      sacrificed 1, 3, and 5 days after treatment. BM cells plated for CFU-GM and
      splenic macrophages were cultured for IL-1 production. Unstimulated splenic
      macrophage production of IL-1 alpha was not different for any group except Day 5
      turpentine animals. TURP induced a significant increase in CFU-GM on Day 1
      compared to that in control (47 +/- 22 vs 21 +/- 11; P < 0.05). SHOCK completely
      abolished this response to TURP. Both the SHOCK and TURP alone increased CFU-GM
      on Day 5 compared to that in CONTROL but there was no additive effect in the
      SHOCK + TURP group. These data show that the BM response to combined soft tissue
      injury and shock (TURP + SHOCK) appears similar to that of SHOCK alone and that
      hemorrhagic shock appears to be a significant immunosuppressive factor in the
      regulation of myelopoiesis following injury.

PMID- 7630141
TI  - A novel synthetic analog of peptide YY, BIM-43004, given intraluminally, is
      proabsorptive.
AB  - Peptide YY (PYY), a proabsorptive hormone, is released into the circulation and
      lumen of the small intestine after a meal. We have recently found that
      intraluminal PYY is proabsorptive in the ileum. The purpose of this study was to
      examine the effects of intraluminal administration of a new substituted PYY (22
      36) analog on intestinal absorption of electrolytes and water. Twelve conditioned
      20-kg dogs had 25-cm jejunal, 25-cm ileal, or 20-cm colonic Thiry-Vella fistulas
      (TVF) surgically constructed under general anesthesia (jejunal and ileal TVF, N =
      6, and colonic TVF, N = 6). After a 2-week recovery period, the animals received
      the intraluminal PYY analog, BIM-43004, in the ileum (200 pmole/kg) or colon (300
      pmole/kg) for 60 min after a 90-min steady-state basal period was confirmed. The
      TVF were perfused with an isotonic buffer solution containing [14C]polyethylene
      glycol as a volume marker. Ion and water transport were measured every 15 min.
      Net water absorptions were significant in the ileum and colon but not in the
      jejunum upon intraluminal administration of the PYY analog, BIM-43004. Colonic
      water absorptions were increased more than twofold above basal absorption rates
      and ileal absorptions were increased more than 1.5-fold upon addition of
      intraluminal BIM-43004. Sodium and chloride ion absorption in the colon and ileum
      paralleled water fluxes. We are describing for the first time a synthetic peptide
      analog of PYY that produces significant water and electrolyte absorption in the
      ileum and colon when administered luminally. This synthetic analog may have
      therapeutic potential in patients with malabsorptive disorders.

PMID- 7630142
TI  - Somatostatin inhibits B-cell secretion via a subtype-2 somatostatin receptor in
      the isolated perfused human pancreas.
AB  - Recently five somatostatin receptor subtypes (SSTR) have been cloned, allowing
      the development of highly specific selective agonists for these SSTR. The present
      study was undertaken to determine which SSTR is responsible for the inhibitory
      effect of somatostatin on islet hormone secretion. Single-pass perfusion of four
      agonists was performed in pancreata obtained from four cadaveric organ donors
      using a modified Krebs-media with 3.9 mM glucose. Sequential 10-min specific
      receptor agonist infusions (5 ng/ml) of DC32-87 (SSTR2), DC25-12 (SSTR3), DC32-97
      (SSTR3), or DC32-92 (SSTR5) were performed in random order separated by 10-min
      basal periods. Infusion of SSTR2 agonist into the isolated perfused human
      pancreas resulted in a significant inhibition of insulin and C-peptide secretion
      (insulin = -1468 +/- 480 pM, P < 0.05, and C-peptide = -2328 +/- 437 pM, P <
      0.05) but not islet amyloid polypeptide or somatostatin. These results suggest
      that the inhibitory effect of somatostatin on B-cell secretion is mediated
      through the subtype-2 receptor within the human islet.

PMID- 7630143
TI  - Donor-specific unresponsiveness to murine cardiac allografts induced by
      intrathymic-soluble alloantigens is dependent on alternate pathway of antigen
      presentation.
AB  - This study extends the finding that intrathymic (IT) inoculation of uv-B
      irradiated donor spleen cells (SC) or soluble alloantigens (Ag) induces
      peripheral tolerance to organ allografts in the rat to the murine cardiac
      allograft model. In our initial experiment, we showed that IT inoculation of uv-B
      irradiated SC combined with transient immunosuppression of the recipient with
      either sublethal TBI or ALS on Day -7 led to donor-specific, long-term cardiac
      allograft survival (> 300 days) in the completely mismatched A/J-to-C57BL/6 mice
      combination. To test our hypothesis that peripheral tolerance induced by IT
      injection of donor Ag is dependent on presentation of the foreign MHC molecule by
      thymic APC to T cell precursors, we examined the effect of IT injection of donor
      APC-free-soluble Ag inoculum obtained from 3 MKCl extracts of purified MHC class
      I resting T cells on cardiac allograft survival in the A/J-to-C3H mice
      combination. The results showed that IT injection of the optimal dose of 500
      micrograms soluble Ag combined with 0.5 ml ALS on Day -7 led to donor-specific
      permanent graft survival (> 200 days). This finding could not be reproduced by
      intravenous administration of soluble Ag, thus confirming the privileged position
      of the thymus in tolerance induction. To further define the role of host APC in
      allorecognition, we studied the presentation of soluble Ag by responder APC in
      MLR. The results showed that primed T cells obtained from A/J skin graft
      sensitized C3H T cells specifically developed alloreactivity to A/J-soluble Ag in
      MLR.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7630144
TI  - Intraperitoneal sodium carboxymethylcellulose administration prevents reformation
      of peritoneal adhesions following surgical lysis.
AB  - Although intraperitoneal administration of sodium carboxymethylcellulose (SCMC)
      prevents the formation of adhesions following laparotomy in rats, it remains
      unknown whether SCMC treatment prevents the recurrence of preformed peritoneal
      adhesions following surgical lysis. Additionally, the optimal amount of SCMC
      required for adhesion prevention, as well as the effects of SCMC upon the healing
      of bowel anastomoses, has yet to be determined. To study this, 114 male rats
      underwent laparotomy and adhesion induction via peeling of the cecal serosa with
      a gauze sponge. Two weeks later, all animals again underwent laparotomy, the
      adhesions were graded, and surgical lysis of adhesions was performed. Following
      this, 3 to 12 ml of either normal saline or 1% SCMC solution was instilled into
      the peritoneal cavity prior to closure. A segment of small bowel was transected
      and reanastomosed prior to administration of SCMC or saline in another group of
      70 rats. After an additional 2 weeks, the animals were sacrificed, the adhesions
      graded, and all the abdominal contents removed for fixation. The results show
      that treatment with high volume (i.e., 12 ml) intraperitoneal SCMC prevents
      reformation of adhesions following surgical lysis. This effect is demonstrated by
      a proportionate and significant decrease in the incidence of intraabdominal
      adhesions associated with administration of increasing amounts of SCMC (P <
      0.05). While high volume SCMC did prevent adhesion of peritoneal structures to
      newly formed small bowel anastomoses, SCMC did not impair anastomotic healing.

PMID- 7630145
TI  - Tolerance and effects of almokalant, a new selective Ik blocking agent, on
      ventricular repolarization and on sino-atrial and atrioventricular nodal function
      in the heart: a study in healthy, male volunteers utilizing transesophageal
      atrial stimulation.
AB  - Almokalant, (4-(3-ethyl(3-propylsulfinyl)propyl)amino)-2-hydroxy-propoxy)-
      benzonitrile), is a newly developed Ik channel blocker that exhibits pure class
      III effects. Using a noninvasive approach with transesophageal atrial stimulation
      (TAS), we wished to identify the dose of almokalant, given as an intravenous
      bolus infusion, that prolonged ventricular repolarization in the healthy human
      heart to an extent of potential clinical interest. Furthermore, we defined the
      electrophysiological effects of this dose on the heart, as well as the
      pharmacokinetics, safety, and tolerance throughout a wide dosing range. In the
      titration part, increasing doses were given to identify the dose that produced a
      reproducible QTend prolongation of approximately 20%. This dose (12.8 mumol) was
      then given in a placebo-controlled, double-blind, cross-over fashion. In the
      double-blind part, almokalant significantly prolonged the QTend intervals during
      sinus rhythm and during TAS at 100 beats/min and increased the effective
      refractory period of the atria (AERP). There was no alteration in either the
      cardiac conduction (PQ and QRS), or blood pressure (BP) sinus node function, or
      the ERP of the atrioventricular (AV) node. Therefore, almokalant exhibited pure
      class III effects with no signs of beta-blockade or unwanted hemodynamic effects.
      The plasma concentration-time curve showed a biexponential decrease with a
      terminal half-life (t1/2) of approximately 3 h. There was a large interindividual
      variation in the plasma concentration at the end of infusion, Cmax. This
      variability diminished considerably 60 min after infusion, and the
      pharmacokinetic characteristics studied appeared to be proportional to the dose.
      The drug was well tolerated, and the only side effect noted was a brief metallic
      taste after a dose of 25.6 mumol. Corresponding to high plasma peak values, T
      wave morphology changes of short duration were observed, sometimes with the
      development of pronounced, biphasic T waves.

PMID- 7630146
TI  - Effects of caffeine on background potassium current in isolated guinea pig
      ventricular myocytes.
AB  - We investigated effects of caffeine on inward rectifier potassium current (Ik1)
      in voltage-clamped ventricular cells by slow ramp depolarization (15 mV/s).
      Caffeine 10 mM applied in the solution bathing the cells consistently reduced the
      slope of the current-voltage (I-V) relation over the range of -80 to -40 mV. This
      effect of caffeine was not prevented by loading cells with BAPTA (1,2-bis(2
      aminophenoxy) ethane N,N,N',N'-tetra-acetic acid) to suppress contraction. In the
      absence of caffeine, reducing extracellular potassium from 5.4 to 2.7 mM caused
      the expected shift of the reversal potential for current in the negative
      direction and increased rectification. In low potassium, 10 mM caffeine continued
      to reduce the slope of the I-V relation. When 2 mM barium was applied to suppress
      Ik1, any effects of 10 mM caffeine were slight or absent. The observations are
      consistent with a blocking action of caffeine on Ik1 in guinea pig ventricular
      myocytes.

PMID- 7630147
TI  - Effects of some novel D-myo-inositol-phosphate derivatives on binding and
      sympathetic transmission.
AB  - The vascular effects of myo-inositol and a series of D-myo-inositol phosphate
      derivatives: D-myo inositol-1-monophosphate (Ins[1]P1), D-myo-inositol-2
      monophosphate (Ins[2]P1), D-myo-inositol-1, 2-biphosphate (Ins[1,2,6]P2), D-myo
      inositol-1,2,6-trisphosphate (Ins[1,2,6]P3, alpha-trinositol; PP56), D-myo
      inositol-1,2,5,6-tetraphosphate (Ins[1,2,5,6]P4), and D-myo-inositol-1,2,3,4,5,6
      hexa-phosphate (InsP6, phytic acid) were studied in binding assays in rat heart
      membranes, in vitro in isolated guinea pig basilar artery, and in vivo in pithed
      rats. In binding assays in rat heart membranes, Ins[1,2,6]P3, Ins[1,2,5,6]P4, and
      InsP6 displaced the binding of [3H] alpha-trinositol [3H]Ins[1,2,6]P3). In the
      isolated guinea pig basilar artery, Ins[1,2]P2 and Ins[1,2,6]P3 inhibited the
      contractile effects of exogenous neuropeptide Y (NPY) in the concentration range
      of 10(-8)-10(-6) M. In pithed Sprague-Dawley rats, Ins[1,2,6]P3 inhibited the NPY
      induced pressor response in the dose range [2 mg/kg (3.8 mumol/kg) combined with
      an infusion of 20 mg/kg/h (38 mumol/kg/h) for 30 min] in which no inhibitory
      effects on the pressor responses were elicited by preganglionic nerve stimulation
      (PNS) or a bolus injection of phenylephrine (Phe). Ins[1,2]P2 had only slight NPY
      inhibitory effects in vivo. We conclude that selected inositol derivatives may
      inhibit the vasopressor effects to NPY in vitro and in vivo. In particular,
      Ins[1,2,6]P3, which most readily inhibited the NPY-induced pressor response in
      vivo, may represent a new class of synthetic nonpeptide drugs, which may inhibit
      the vascular effects of NPY without binding to the NPY receptor itself.

PMID- 7630148
TI  - Systemic and cerebral hemodynamic responses to the noncompetitive N-methyl-D
      aspartate (NMDA) antagonist CNS 1102.
AB  - The excitatory amino acid antagonists are being developed as neuroprotective
      drugs aimed at limiting ischemic neuronal damage. Their hemodynamic and
      neurologic side effects are important in assessing safety and tolerability. We
      studied CNS 1102, a high-affinity noncompetitive N-methyl-D-aspartate (NMDA)
      receptor-channel antagonist, in normal volunteers. The effects of 2 mg CNS 1102
      were assessed in a single-blind, placebo-controlled, fixed-dose, cross-over trial
      comparing administration by intravenous infusion for 15 min or bolus for 2 min in
      8 healthy male subjects. Cerebral hemodynamics were studied with carotid and
      vertebral duplex ultrasound imaging, common carotid artery walltracking, and
      middle cerebral artery velocity readings. CNS 1102 administration was associated
      with light-headedness, mild disorientation, perioral and peripheral paresthesias,
      and flushing. Mean arterial blood pressure (MAP) increased significantly from
      baseline 1 h after CNS 1102 administration, with a maximal increase of 17 mm Hg
      over placebo. Pulse rate was unchanged. Common carotid artery pulsatility
      decreased by 38.4% [8.3-64.5, 95% confidence interval (CI)] and vertebral
      pulsatility by 43.8% [11.5-74.1], both p < 0.02. No significant differences were
      detected for other velocity and flow parameters. Middle cerebral artery mean
      velocity increased by 4.6 cm/s (1.6-7.8 cm/s) and diastolic velocity by 4.6 cm/s
      (2.4-7.3 cm/s) (both p < 0.01), but systolic velocity was unchanged. The middle
      cerebral pulsatility index decreased by 11% (3.8-16.1), p < 0.001. CNS 1102 is
      well tolerated at a fixed dose of 2 mg in normal volunteers. Cerebral arteriolar
      constriction is inferred from the ultrasound results.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7630149
TI  - Discordant effects of dietary L-arginine on vascular structure and reactivity in
      hypercholesterolemic rabbits.
AB  - We investigated the effect of dietary supplementation of L-arginine (L-Arg), the
      precursor of endothelial nitric oxide (NO), on endothelium-dependent and
      endothelium-independent vascular responses, as well as vascular structure, in the
      abdominal aorta of hypercholesterolemic rabbits. Rabbits were fed (a) normal
      rabbit chow, (b) 1% cholesterol diet, or (c) 1% cholesterol diet supplemented
      with 2.25% L-Arg HCl in drinking water. After 10 weeks, the abdominal aorta was
      harvested for study of vascular reactivity and histomorphometry. L-Arg did not
      affect serum cholesterol levels. Histomorphometric analysis demonstrated an
      eightfold reduction in intimal thickening in the abdominal aorta of the arginine
      supplemented hypercholesterolemic rabbits. By contrast, the effects on vascular
      reactivity were subtle. Contraction to norepinephrine (NE) was not altered by
      hypercholesterolemia or L-Arg. Contraction to acetylcholine (ACh) was increased
      in hypercholesterolemic animals; this was normalized by dietary arginine
      supplementation. Relaxation to nitroglycerin (NTG) was not altered by
      hypercholesterolemia but was attenuated in the arginine-supplemented rabbits.
      Endothelium-dependent relaxation to ACh was impaired in both hypercholesterolemic
      groups. Dietary L-Arg has a dramatic antiatherogenic effect in
      hypercholesterolemic rabbits. This effect is associated with rather slight
      changes in vascular reactivity that are suggestive of a slight increase in NO
      elaboration by the endothelium. The discordance between the effects of dietary
      arginine on vascular structure and reactivity suggests that the antiatherogenic
      effects of the NO precursor may not be mediated entirely by its effect on the
      endothelium.

PMID- 7630150
TI  - Influence of nonpeptide angiotensin II receptor antagonist, losartan, on
      neurogenic vasoconstriction.
AB  - The influence of the nonpeptide angiotensin antagonist losartan on
      andrenergic/purinergic cotransmission in pithed rat preparation before and after
      treatment with prazosin (alpha 1-antagonist), rauwolscine (alpha 2-antagonist),
      and/or the P2x desensitizing agent alpha, beta-methylene ATP (mATP) was examined.
      Stimulation of the spinal sympathetic outflow (T6-T8) through the pithing rod
      (1.0-cm electrode) at supramaximal voltage, 0.05-ms pulses, at different
      frequencies (1-40 Hz) evoked biphasic responses. Changes in diastolic blood
      pressure (DBP) were assessed at the early peak after the 1.0-train. The
      vasopressor responses to sympathetic nerve stimulation were partially blocked by
      prazosin, rauwolscine, mATP, and losartan. Administration of prazosin or mATP but
      not rauwolscine as compared with losartan alone could further reduce vasopressor
      responses to sympathetic nerve stimulation. In rats treated with losartan and
      either prazosin or rauwolscine, administration of mATP further reduced
      vasoconstrictor responses to sympathetic nerve stimulation. In contrast,
      rauwolscine did not further reduce vasoconstriction due to sympathetic nerve
      stimulation in rats that had received losartan and prazosin combined.
      Furthermore, the inhibitory actions of mATP were significantly greater in rats
      that had received losartan and prazosin as compared with rats that received
      losartan and rauwolscine. The results indicate that losartan in vivo is most
      effective in inhibiting nerve-mediated alpha 2-adrenoceptor responses as opposed
      to either alpha 1-adrenoceptor or P2x-purinoceptor responses.

PMID- 7630151
TI  - Hemodynamic effects of angiotensin II and the influence of angiotensin receptor
      antagonists in pithed rabbits.
AB  - We investigated the cardiovascular effects of angiotensin II (AII) and the
      influences of four angiotensin receptor antagonists: losartan, PD123177, BIBS 39,
      and BIBS 222 in the pithed rabbit preparation. AII (0.03-10 nmol/kg) elicited a
      dose-dependent increase in blood pressure (BP), left ventricular pressure (LVP),
      LV end-diastolic pressure (LVEDP), dP/dtmax, and heart rate (HR). The maximal
      hypertensive effect of AII is comparable to that of norepinephrine (NE), but its
      effects on LVEDP and HR are weaker than those of NE. On a molar base, AII is
      approximately 27 times more potent than NE. Propranolol (0.5 mg/kg i.v.) did not
      significantly influence the AII-induced increase in diastolic BP (DBP) and LVEDP,
      but it abolished AII-induced positive chronotropic effects over the entire dose
      range of angiotensin AII studied. Losartan, but not PD123177, shifted the dose
      response curves for AII to the right in a parallel manner. BIBS 39 and BIBS 222
      also caused rightward shifts of the AII dose-response curve. These experiments
      indicate that in propranolol-treated pithed rabbits AII causes vasoconstrictor
      effects in both resistance vessels and in the venous system, which are both
      mediated by AT1- but not by AT2-receptors. The AII-induced positive chronotropic
      effect is an indirect action mediated by the stimulation of postsynaptic beta 1
      adrenoceptors. BIBS 39 and BIBS 222, two new nonpeptide angiotensin receptor
      blockers that have affinity for both AT1- and AT2-receptors are also potent
      antagonists of the cardiovascular effects of AII in pithed rabbits.

PMID- 7630152
TI  - Dopaminergic drugs in congestive heart failure: hemodynamic and neuroendocrine
      responses to ibopamine, dopamine, and dihydroergotoxine.
AB  - Ibopamine has hemodynamic and neurohumoral effects potentially useful for the
      treatment of congestive heart failure (CHF), but its mechanism of action is not
      completely clear. To evaluate the role of dopaminergic receptor stimulation in
      the hemodynamic and neurohumoral activity of ibopamine, we compared the effects
      of ibopamine, 100 mg orally (p.o.) with those of the dopamine 2, 4, and 6
      micrograms/kg/min intravenously (i.v.) and of the DA2 agonist dihydroergotoxine 6
      micrograms/kg i.v. in 13 patients with chronic CHF [left ventricular ejection
      fraction (LVEF) < or = 35%]. All patients underwent right heart Swan-Ganz
      catheterization with determination of hemodynamic parameters at baseline, after
      30 min of infusion of each dose of dopamine (DA) and < or = 6 h after ibopamine
      and dihydroergotoxine administration. Blood samples for the assessment of plasma
      renin activity (PRA), aldosterone, norepinephrine (NE), and epinephrine (Epi)
      were also obtained. Ibopamine induced a peak 21% increase of cardiac index (CI)
      with a 23 and 25% increase in stroke volume (SV) and stroke work indexes (SWI),
      respectively, and an 18% reduction in systemic vascular resistance (SVR). Similar
      changes were observed after DA infused at the doses of 2 and 4 micrograms/kg/min,
      whereas with the dose of 6 micrograms/kg/min heart rate (HR) increased by 23% and
      SV index (SVI) did not change further. Dihydroergotoxine administration induced
      only a significant 9% decrease in mean arterial pressure (MAP), with a 13%
      reduction in SVR.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7630153
TI  - 15-Hydroxyeicosatetraenoic acid and diabetic endothelial dysfunction in rabbit
      aorta.
AB  - We examined the effects of diabetes on eicosanoid metabolism and endothelium
      dependent relaxation in isolated aorta from alloxan-induced diabetic rabbits and
      that from normal rabbits incubated in increased concentrations (44 mM) of glucose
      in vitro for 6 h. Immunoreactive 15-hydroxyeicosatetraenoic acid (HETE) was
      assayed in the incubation media of isolated aortic segments. Basal and
      acetylcholine (ACh)-stimulated release of 15-HETE was significantly greater in
      aorta of diabetic animals as compared with those of normal rabbits. Incubation of
      aortic segments from normal rabbits in increased concentrations of glucose caused
      a significant increase in basal and ACh-stimulated release of 15-HETE; and the
      release was significantly greater in aortic segments with endothelium than in
      segments without endothelium. Basal and ACh-stimulated release of 15-HETE was
      inhibited by indomethacin, a cyclooxygenase inhibitor. 15-HETE caused
      contractions of aortic rings that were inhibited by the prostaglandin H2 (PGH2)
      thromboxane A2 (TXA2) receptor blocker SQ-29548, but not by the TXA2 synthase
      inhibitor carbethoxyhexyl imidazole or indomethacin. Treatment of aortic rings
      with subthreshold concentrations of 15-HETE impaired ACh-induced relaxation; this
      was prevented by treatment with SQ-29548. Thus, abnormal release of endothelium
      derived 15-HETE may play a role in endothelial cell dysfunction and increased
      vasoconstriction in diabetes by a mechanism that involves interaction with
      PGH2/TXA2 receptors.

PMID- 7630154
TI  - Interference of angiotensin-converting enzyme inhibition with vasoactive peptides
      in the coronary circulation of dogs.
AB  - The coronary effects of angiotensin-converting enzyme (ACE) inhibitors and their
      mechanisms of action are not well understood. Because these drugs may interfere
      with hormone systems other than the reninangiotensin system (RAS), we studied
      modulation of the coronary effects of neurotensin, neuropeptide Y (NPY), and
      endothelin-1 (ET-1) by pretreatment with captopril in anesthetized, open-chest
      dogs. The left anterior descending coronary artery (LAD) was cannulated and
      perfused at a pressure equal to mean aortic blood pressure. Coronary blood flow
      (CBF) was measured by an electromagnetic flowmeter, subendocardial segment length
      by ultrasonic crystals. ACE inhibition (captopril 0.25 mg/kg), as an
      intracoronary (i.c.) injection, followed by an intracoronary infusion (0.25
      mg/kg/h) did not affect the relative vasoconstrictor effects of ET-1 (10(-4)-10(
      1) micrograms/kg i.c.) or neuropeptide Y (10(-3)-1 microgram/kg i.c.). However
      preinjection flow of a second dose-response curve of ET-1 was significantly
      higher in captopril-treated as compared with control animals. The increase in CBF
      induced by neurotensin (10(-3)-1 microgram/kg i.c.) was potentiated by captopril
      (40 +/- 14% after vs. 20 +/- 9% before captopril, p < 0.01, at the highest dose
      used). Changes in hemodynamics or in regional myocardial function could not
      explain altered effects of neurotensin. We therefore conclude that ACE inhibition
      does not interfere with the acute vasoconstrictor effects of ET-1 or NPY in this
      canine model but may reverse the long-term tonic coronary constrictor effect of
      ET-1. Potentiation of the neurotensin effect on CBF might be due to prevention of
      hydrolysis of neurotensin or to a cyclooxygenase-dependent mechanism.

PMID- 7630155
TI  - Effects of heparin on aortic versus venous smooth muscle cells: similar binding
      with different rates of [3H]thymidine incorporation.
AB  - The mechanisms resulting in the high incidence of stenoses of coronary venous
      bypass grafts are still unclear. Heparin, a potential inhibitor of cellular
      proliferation, neither inhibits intimal hyperplasia in animal models of vein-to
      artery grafting nor prevents graft stenosis when administered to patients. We
      studied the effects of heparin on cultured pairs of human aortic and venous
      smooth muscle cells (SMC) obtained during coronary bypass surgery from patients
      with no history of previous restenosis or graft failure. DNA synthesis was
      measured as [3H]thymidine incorporation after stimulation with 10% fetal calf
      serum (FCS). Heparin (100 micrograms/ml) inhibited DNA synthesis of aortic SMC to
      64 +/- 14% (mean +/- SEM), whereas it stimulated DNA synthesis of venous SMC to
      136 +/- 23% (10% FCS alone = 100%; p = 0.01, Wilcoxon signed-rank test, n = 7).
      Binding studies with [3H]heparin showed no significant differences of Kd values
      and number of binding sites per cell between SMC derived from aorta or vein that
      could account for the lack of heparin inhibition of venous SMC DNA synthesis.
      These data suggest an inherent difference in the heparin susceptibility that may
      explain the failure of heparin to inhibit intimal proliferation in vein grafts.

PMID- 7630156
TI  - Comparison of the stereoselective effects of a thiadiazinone derivative on
      contractile parameters and protein phosphorylation in the mammalian ventricle.
AB  - In papillary muscles from reserpinized guinea pigs, EMD 57033, the most potent
      Ca(2+)-sensitizer known, effectively increased force of contraction (FOC) and
      concomitantly increased duration of contraction. In isolated 32P-labeled guinea
      pig ventricular cardiomyocytes, EMD 57033 increased the phosphorylation state of
      phospholamban as well as the inhibitory subunit of troponin, which are usually
      linked to reductions in contraction time. Therefore, EMD 57033 dissociates
      phospholamban-phosphorylation and effects on contractile parameters, probably
      owing to its strong Ca(2+)-sensitizing properties.

PMID- 7630157
TI  - Troponin C-mediated calcium sensitization induced by levosimendan does not impair
      relaxation.
AB  - Levosimendan is a novel positive inotropic drug targeted to increase contraction
      force of the heart through its calcium-dependent binding to troponin C (cTnC). We
      investigated the calcium-sensitizing effect of levosimendan on contractile
      proteins as well as its positive inotropic and lusitropic effects in paced guinea
      pig papillary muscle. We also studied the effect on energy consumption of myosin
      actin crossbridges in a myosin ATPase assay. The calcium sensitization induced by
      levosimendan in fibers skinned with saponin was dependent on the perforation
      velocity of cell membranes. Levosimendan was almost ineffective in slowly
      perforated fibers, but was the most potent calcium sensitizer in fibers with
      rapidly perforated cells. The perforation-dependent calcium sensitization was
      probably due to changes in phosphorylation state of contractile proteins during
      the slow dissection of fibers. It is noteworthy that the calcium-sensitizing
      effect of levosimendan was not affected by acidic pH. Levosimendan at
      therapeutically relevant (0.3-10 microM) concentrations markedly increased
      calcium sensitivity both at pH 6.7 and 7.0, being more potent than EMD 53998,
      pimobendan, and MCI-154. The lack of effect of levosimendan on maximum tension
      supports the hypothesis that levosimendan increases calcium sensitivity through
      its action on cTnC. Unlike EMD 53998, levosimendan did not increase myosin ATPase
      activity, indicating that it did not increase the cycling rate of myosinactin
      crossbridges. In paced papillary muscles, levosimendan induced positive inotropic
      effect without changing relaxation time. Thus, levosimendan was devoid of the
      main negative factors described for calcium sensitizers.

PMID- 7630158
TI  - Different localization of ETA and ETB receptors in the hyperplastic vascular
      wall.
AB  - We investigated which subtypes of endothelin-1 (ET-1) receptors are involved in
      the pathogenesis of angioplasty-induced lesion formation in the rabbit carotid
      artery. Four weeks after removing endothelial cells (EC), we noted a marked
      intimal hyperplasia. The Bmax values for [125I]ET-1 and [125I]IRL1620 (an agonist
      for the ETB receptors) bindings were greater in the hyperplastic artery, without
      changes in Kd values. [125I]ET-1 binding was completely inhibited by unlabeled ET
      1 and Ro 46-2005, a mixed-type antagonist for the ETA and ETB receptors, but
      partially by BQ123, a selective antagonist for ETA receptors, and IRL1620. The
      [125I]ET-1 binding sites not inhibited with BQ123 were significantly increased in
      the hyperplastic artery. The binding study suggested the presence of non-ETA/non
      ETB receptors. The rank order of the increasing ratio in the density of receptors
      was ETB > putative non-ETA/non-ETB > total ET-1 receptors > ETA. The
      histochemical experiments with biotinylated ET-1 at lysine-9 side chain alone or
      in combination with unlabeled ET-1, BQ123, Ro 46-2005, or IRL1620, showed the ETA
      receptors to be localized mainly in the media, whereas the ETB receptors
      localized mainly in the neointima. These results suggest that the increased ET-1
      receptors, especially ETB and/or putative non-ETA/non-ETB, are closely related to
      the occurrence of the intimal hyperplasia after endothelial removal.

PMID- 7630159
TI  - Profibrillatory effects of lidocaine in the acutely ischemic porcine heart.
AB  - Because recent clinical studies have failed to show evidence of the benefit of
      lidocaine in the arrhythmias occurring in the early stage of myocardial
      infarction and have even shown an increased mortality in patients thus treated,
      we investigated the value of lidocaine as a protective agent against ventricular
      fibrillation related to myocardial ischemia in the in situ heart of anesthetized
      open-chest pigs subjected to transient total occlusion of the proximal left
      anterior descending coronary artery (LAD) under ventricular pacing at a constant
      high rate. Vulnerability to the fibrillatory process induced by coronary
      occlusion was assessed both by time to onset of ventricular fibrillation (TF) and
      by electrical ventricular fibrillation threshold (EFT) determined after coronary
      occlusions of increasing duration (30, 60, 120, 180 s). Monophasic action
      potential (MAP) was recorded concurrently in the nonischemic and ischemic areas.
      Lidocaine, even in relatively high doses (2-4 mg.kg-1), did not prolong TF, nor
      did it increase EFT. On the contrary, TF was significantly shortened and EFT was
      significantly decreased (15-30%) at the maximal concentrations of lidocaine, with
      return to control values in 40-60 min. Therefore, lidocaine tends to increase the
      risk of ischemic ventricular fibrillation (VF): It fails to control the extreme
      enhancement of excitability and worsens conduction disorders, even though it
      decreases normal conduction only slightly. Use of lidocaine against rhythm
      disorders in acute myocardial infarction (AMI), is at least debatable and
      probably contraindicated.

PMID- 7630160
TI  - Role of the sympathoadrenal axis in the cardiovascular response to cocaine in
      conscious unrestrained rats.
AB  - We investigated the role of peripheral sympathetic neurons and the adrenal
      medulla in the cardiovascular responses to cocaine in conscious, unrestrained
      Sprague-Dawley rats. Surgical adrenal demedullation (ADM) and/or chemical
      peripheral sympathectomy was used to eliminate one or both components of the
      sympathoadrenal axis. Phentolamine (5 mg/kg i.v.) was used to evaluate whether
      cocaine elicited epinephrine (EPI) release from the adrenal medulla. Significant
      EPI release by cocaine would result in "epinephrine reversal" after phentolamine
      pretreatment. Cocaine (2.5 mg/kg i.v.) was used in all experiments except the
      dose-response relationship study. In normal rats, cocaine caused a transient
      increase in mean blood pressure (MBP). Pretreatment with phentolamine reversed
      this BP response and this depressor effect was blocked by propranolol (2 mg/kg
      i.v.) suggesting that the pressor effect of cocaine was mediated by EPI. Chemical
      sympathectomy alone partially inhibited the pressor effect of cocaine, but
      pretreatment with phentolamine still reversed the residual action of cocaine on
      MBP at this time. Two weeks after ADM, the effect of cocaine on MBP was not
      significantly different from that of the sham-operated rats. However,
      pretreatment with phentolamine inhibited but did not reverse the effect of
      cocaine on MBP at that time. In rats with both ADM and chemical sympathectomy,
      cocaine caused only a decrease in MBP that was not blocked by propranolol or
      atropine methylnitrate, presumably because of its direct depressive actions.
      Results of this study suggest that both peripheral sympathetic neurons and the
      adrenal medulla play important roles in the cardiovascular actions of cocaine.

PMID- 7630161
TI  - Nitrovasodilators ITF 296 and isosorbide dinitrate exert antiischemic activity by
      dilating coronary penetrating arteries.
AB  - We examined the effect of the novel nitrovasodilator ITF 296 and isosorbide
      dinitrate (ISDN) on myocardial blood flow (BF) distal to a coronary artery
      stenosis. Eleven dogs with a Doppler velocity probe, hydraulic occluder, and
      indwelling microcatheter in the left anterior descending coronary artery (LAD)
      were studied during treadmill exercise in the presence of a coronary artery
      stenosis. On separate days, the effects of ITF 296 in doses of 4 and 20
      micrograms/kg/min i.v. or ISDN 20 micrograms/kg/min i.v. were compared. Coronary
      pressure distal to the stenosis was maintained constant during the control period
      and after administration of either nitrovasodilator. Neither ITF 296 nor ISDN
      significantly altered heart rate (HR), arterial blood pressure (BP), or left
      ventricular end-diastolic pressure (LVEDP). In the presence of a stenosis that
      decreased distal coronary pressure to 58 +/- 4 mm Hg, mean myocardial BF measured
      with microspheres was 0.91 +/- 0.08 ml/min/g in the LAD-dependent region and 2.36
      +/- 0.11 ml/min/g in the posterior control region, respectively. With no change
      in distal coronary pressure, ITF 296 increased mean BF in the LAD region to 1.25
      +/- 0.05 ml/min/g (4 micrograms/kg/min i.v.) and 1.40 +/- 0.10 ml/min/g (20
      micrograms/kg/min i.v.), whereas ISDN (20 micrograms/kg/min i.v.) increased flow
      to 1.28 +/- 0.18 ml/min/g (each p < 0.05). The increase in BF occurred
      exclusively in the deeper layers, with no change in subepicardial BF.
      Consequently, the endocardial/epicardial (endo/epi) BF ratio increased from 0.33
      +/- 0.04 during control stenosis to 0.70 +/- 0.10 after ITF 296 (20
      micrograms/kg/min), and to 0.56 +/- 0.08 after ISDN (each p < 0.05). Neither ITF
      296 nor ISDN had an effect on myocardial BF in the normally perfused control
      region. Therefore, both ITF 296 and ISDN improved BF to the deeper myocardial
      layers distal to a coronary artery stenosis. This effect occurred without
      alterations in stenosis severity or diastolic intraventricular pressure,
      suggesting that these agents act by dilating the penetrating arteries which
      deliver BF to the subendocardium.

PMID- 7630162
TI  - Role of Na+/phosphate-cotransporter in myocardial contractile responses to alpha
      1-agonist.
AB  - The interaction of cardiac sodium/phosphate (Na+/Pi)-cotransporter and the
      phosphoinositide pathway (PIP) in influencing myocardial contraction was
      investigated. Specifically, the study was performed to determine if myocardial
      positive inotropic response (+dP/dt) to phenylephrine (PE, an activator of PIP)
      can be potentiated by inorganic phosphate (Pi, the substrate of Na+/Pi
      cotransporter). Contractile responses of the isolated perfused rat heart were
      studied in conditions of controlled extracellular calcium activity and constant
      preload. The data showed that phenylephrine-induced increase in +dP/dt was
      potentiated by Pi. Prazosin inhibited this increase in +dP/dt, indicating alpha 1
      adrenergic involvement. This Pi-potentiated increase in +dP/dt was also inhibited
      by phosphonoformate (PFA); however, only partial inhibition was obtained with
      concentrations of PFA that selectively inhibited Na+/Pi-cotransporter.
      Isoproterenol-induced increase in +dP/dt was not potentiated by Pi, showing that
      potentiation of +dP/dt is not a common effect of Pi. The data support an
      important interaction between PIP and Na+/Pi-cotransporter in regulating
      myocardial contraction.

PMID- 7630163
TI  - Inhibition of norepinephrine and caffeine-induced activation by ryanodine and
      thapsigargin in rat mesenteric arteries.
AB  - We examined the effects of ryanodine and thapsigargin on changes in cytoplasmic
      [Ca2+] (Cai) and muscle tension in rat mesenteric resistance arteries induced by
      norepinephrine (NE) and caffeine. Both ryanodine and thapsigargin markedly
      inhibited the increase in Cai and contractile responses to caffeine in
      physiological saline and to NE and caffeine in calcium-free conditions. In
      contrast, peak responses to potassium depolarisation and NE in physiological
      saline appeared little affected, although time taken to achieve 50% of peak
      response after addition of NE was slowed after ryanodine and thapsigargin
      treatment. Neither ryanodine nor thapsigargin altered resting tone or Cai or the
      Ca2+ sensitivity of contraction under depolarized conditions. The NE
      concentration-response relationship was not significantly altered after ryanodine
      or thapsigargin. Ryanodine and thapsigargin inhibit the release of intracellular
      Ca2+ stores by NE and caffeine. Inhibition of release of intracellular Ca2+ by NE
      has only slight effects on contractile responses of mesenteric resistance
      arteries when extracellular Ca2+ is present.

PMID- 7630164
TI  - Effects of novel, nonpeptide vasopressin antagonists on progressive
      nephrosclerosis in rats.
AB  - Effects of novel, nonpeptide vasopressin V1 and V2 receptor antagonists on
      partially nephrectomized and salt-loaded spontaneously hypertensive rats (SHR),
      which develop severe hypertension and progressive nephrosclerosis, were
      investigated. SHR were 5/6-nephrectomized and fed a high salt diet. The rats were
      divided into four groups: group 1 was an untreated control, group 2 received the
      V1 antagonist OPC-21268, group 3 received the V2 antagonist OPC-31260, and group
      4 received both the V1 and V2 antagonists. The V1 antagonist alone or combined
      with the V2 antagonist significantly decreased the increase in blood pressure
      (BP) of groups 2 and 4 rats, but the V2 antagonist alone did not reduce the
      increase in BP of the group 3 rats. The V2 antagonist alone or combined with the
      V1 antagonist induced a significant diuresis of rats in groups 3 and 4. The
      increase in urinary protein excretion and the progression of renal hyaline
      arteriolosclerosis were attenuated by the V1 antagonist with or without the V2
      antagonist in rats in groups 2 and 4, but not by the V2 antagonist alone in rats
      in group 3. This implies that the progressive nephrosclerosis in SHR with partial
      renoablation and salt-loading was associated with V1 agonism.

PMID- 7630165
TI  - Follow-up after treatment for breast cancer: how much is too much?

PMID- 7630166
TI  - Surgical treatment of patients with gastric carcinoma and duodenal invasion.
AB  - We retrospectively examined the extent of invasion of gastric cancer with
      duodenal involvement in order to design pertinent surgical procedures that may
      lead to a better prognosis. Examinations were made on excised tissues from 650
      patients who underwent gastrectomy for adenocarcinoma in the gastric antrum. In
      95 patients, the cancer cells extended to beyond the pyloric ring. Spread into
      the duodenum was limited to within 2 cm in 76% of the patients and to within 3 cm
      in 81%. In addition to high rates of metastasis in group 1 and 2 lymph nodes,
      some group 3 lymph nodes also were involved, and more frequently so in cases with
      duodenal invasion than in those without such invasion (P < 0.01). The 5-year
      survival rate for patients with duodenal invasion was 35.4% when a curative
      resection was done. For patients with advanced adenocarcinoma with duodenal
      invasion, gastrectomy with resection of 3-4 cm of the duodenum and dissection of
      group 1, 2, and 3 lymph nodes were recommended.

PMID- 7630167
TI  - Tumor necrosis factor alpha stimulates gluconeogenesis from alanine in vivo.
AB  - An increase in gluconeogenesis contributes to the cachexia seen in severe injury,
      sepsis, and malignancy by converting amino acids from skeletal muscle to glucose.
      Since tumor necrosis factor alpha (TNF alpha) may mediate this cachexia, we
      examined the effect of this cytokine on gluconeogenesis. Twenty-eight male
      Fischer rats were injected intraperitoneally with TNF alpha (250 micrograms/kg)
      or saline, and after 4 hours, isolated hepatocytes were obtained by in situ
      collagenase liver perfusion. Hepatocytes were incubated with alanine (10 mM), and
      rates of gluconeogenesis were determined. Plasma lactate, glucose, insulin,
      glucagon, cortisol, and amino acids were measured. TNF alpha administration
      resulted in a 50% increase in gluconeogenesis from alanine (P < 0.05) and a three
      fold increase in plasma glucagon (P = 0.01). Total and glucogenic plasma amino
      acids decreased with TNF alpha injection (P < 0.05). In vivo TNF alpha causes an
      increase in hepatic gluconeogenesis associated with increased plasma glucagon.

PMID- 7630168
TI  - Curative resection of gastric cancer: limitation of peritoneal lavage cytology in
      predicting the outcome.
AB  - Patients with stage T3N0-2M0 gastric carcinoma (n = 108) were studied for
      relevant prognostic factors. Peritoneal lavage cytology (PLC) was performed in
      all. In univariate analysis, 5-year survival rates were better with smaller
      serosal invasion (diameter < 3.0 cm vs. > or = 3.0 cm, 61% vs. 37%, P < 0.05) and
      fewer metastatic nodes (< or = 5 vs. > or = 6, 57% vs. 29%, P < 0.05). In
      multivariate analysis, only these two factors were significant. The predictive
      value of PLC was not shown in both univariate and multivariate analyses.
      Peritoneal recurrence occurred in 14 (22%) of 77 patients with negative PLC, and
      in 3 (18%) of 17 with positive PLC, the difference being not significant. Our
      results indicate that PLC is insensitive in predicting the development of
      peritoneal recurrence. Its role in the estimation of survival is limited, as many
      will die of visceral or locoregional recurrence if not of peritoneal
      dissemination.

PMID- 7630169
TI  - Vocal cord paralysis in patients with thoracic esophageal carcinoma.
AB  - Of 478 consecutive patients with intrathoracic esophageal carcinoma, 5% had vocal
      cord paralysis. In two thirds of the patients with vocal cord paralysis, the
      paralysis was caused by a metastatic lymph node located along the recurrent
      laryngeal nerve. These findings indicate that the possibility exists for radical
      surgery by esophagectomy and resection of the metastatic lymph node infiltrating
      the recurrent laryngeal nerve, even in patients with vocal cord paralysis.
      However, in only two patients was radical surgery accomplished. None of the 24
      patients with paralysis survived without disease for more than 1 year. Thus, in
      patients with vocal cord paralysis, the need for combined therapy should be
      emphasized.

PMID- 7630170
TI  - Immunohistochemically demonstrated expression of HLA-DR antigen in colorectal
      adenocarcinomas and its relation to clinicopathological features.
AB  - We studied 148 colorectal adenocarcinomas to clarify any correlation between HLA
      DR antigen expression on tumor cells and histopathological features. Paraffin
      sections of formalin-fixed tissues were stained with HLA-DR antigen using the
      indirect immunoperoxidase technique. All the tumor tissues were divided into two
      groups, depending on the incidence of HLA-DR-positive cells (greater and lesser
      than 50%). Carcinoma tissues with a higher incidence showed less mural invasion,
      lymphoductal invasion, venous invasion, lymphonodular metastasis, and peritoneal
      metastasis. Tissues with a high HLA-DR reactivity were more often observed for
      Dukes' A and B stages, whereas those with a low HLA-DR positivity were frequently
      Dukes' C and D stages. As for the cumulative survival rate, the group with high
      HLA-DR expression demonstrated significantly better survival. We speculate that
      HLA-DR expression by colorectal cancer cells exerts a favorable influence on
      clinical course.

PMID- 7630171
TI  - Tumor ploidy as a risk factor for disease recurrence and short survival in
      surgically-treated Dukes' B2 colon cancer patients.
AB  - The risk factors for colon cancer recurrence following a curative intent surgery
      include the presence of metastatic disease, the tumor location and size, number
      of positive lymph nodes, the presence of adhesions, perforation, bowel
      obstruction, depth of invasion, histological grade, percentage of S-phase
      content, and cell kinetic profile. The DNA content of colon cancers in 20 Dukes'
      B2 patients in follow-up evaluation at our center, who relapsed, either locally
      or systemically following surgical treatment was measured by image analysis. The
      data were pair-matched for age, sex, tumor site, and grade with 20 Dukes' B2
      patients who had no evidence of disease. Aneuploidy occurred in 16 (80%) patients
      with recurrence, as compared with only in 8 (40%) in the control group.
      Aneuploidy was associated with significantly higher tumor recurrence rate (P =
      0.024) and shorter overall survival (P < 0.002). Our data may point out a
      possible indication for systemic adjuvant chemotherapy in Dukes' B2 colon cancer
      patients who have aneuploid tumors on image analysis. This warrants further
      investigation in a prospective controlled randomized study.

PMID- 7630172
TI  - Early experience with videothoracoscopic hydrodissection pleurectomy in the
      treatment of malignant pleural effusion.
AB  - Parietal pleurectomy is our preferred procedure for management of malignant
      pleural effusion. However, the morbidity of a major thoracotomy has precluded all
      but highly selected patients from the conventional (open) procedure. Recently, we
      have been able to perform parietal pleurectomy by means of a video-assisted,
      thoracoscopic technique. We have retrospectively analyzed the results of this
      procedure performed on 11 patients between March 1993 and February 1995. These
      patients ranged in age from 40 to 87 years of age, with a mean age of 61.5 years.
      Primary tumors were non-small cell lung cancer (5), breast cancer (4),
      mesothelioma (1), and unknown (1). There was one operative mortality (9.1%). All
      were relieved of symptoms of pleural effusion. Median survival was 128 days.
      Early experience indicates we are accomplishing an operation equivalent to that
      formerly performed by "open" technique. If continued results are similar to our
      initial experience, we will be able to offer this superior palliation of
      malignant pleural effusion to a wider range of patients.

PMID- 7630173
TI  - Characteristics of non-small cell lung cancer 3 cm or less in diameter.
AB  - We retrospectively investigated 308 cases of non-small cell lung cancer of < or =
      3 cm diameter. There were 204 adenocarcinomas, 78 squamous cell carcinomas, 15
      large cell carcinomas, and 11 other carcinomas. According to TNM staging, there
      were one case stage 0, 208 stage I, 22 stage II, 49 stage IIIA, 15 stage IIIB,
      and 13 cases stage IV. T1 disease was seen in 262 cases, T2 in 19, T3 in 10, T4
      in 16, and Tis in 1. N0 disease was seen in 217 cases, N1 in 30, N2 in 60, and N3
      in 1. The 5-year survival rate of all cases was 63%. There were statistically
      significant differences among T status (T1 vs. T3, T4), N status (N0 vs. N1, N2),
      and M status (M0 vs. M1) (P < 0.01). The 5-year survival rates of cases with
      adenocarcinoma and squamous cell carcinoma were 60% and 64%, respectively. In 204
      cases of adenocarcinoma, T3 disease was found in one case, T4 disease in 15 (7%),
      and nodal involvement (N1 + N2) was present in 69 (34%). In 78 cases of squamous
      cell carcinoma T3 was seen in 6 (8%), T4 in 1, and nodal involvement in 14 (18%).
      The incidence of T3 disease, T4, and N(+) varied significantly according to
      histology (P < 0.05). Our investigation suggested that cases of small-sized lung
      cancer were often at an advanced stage at detection, and that the spread of
      disease differed according to histology. The patient with small-sized lung cancer
      should be offered a standard operation regardless of histology.

PMID- 7630174
TI  - Macroscopic intraoperative diagnosis of serosal invasion and clinical outcome of
      gastric cancer: risk of underestimation.
AB  - Data on 715 Japanese patients with gastric cancer were studied retrospectively
      with regard to the relationship between macroscopic and microscopic diagnoses of
      serosal invasion and clinicopathological factors affecting the accuracy of the
      macroscopic diagnosis. Although there was no macroscopic evidence of serosal
      invasion intraoperatively (S0 or S1), there was histological evidence of cancer
      cells on the serosal surface in 69 patients (9.7%). In these serosal invasion
      positive cases, the tumors were larger; were located more commonly in the upper
      third, lesser and greater curvatures of the stomach; were Borrmann type 3 or type
      4 tumors, and of an undifferentiated histologic type with an infiltrative growth
      pattern more commonly, and had more extensive lymphatic and vascular vessel
      invasion and lymph node metastasis (P < 0.01). Total gastrectomy was done more
      often for the serosal invasion-positive group, but the extent of lymph node
      dissection was comparable. Cases of a noncurative resection because of a positive
      surgical margin were more frequent in the serosal invasion-positive group (8/69
      vs. 14/646, P < 0.01), and most had undifferentiated and infiltrative cancers.
      The 10-year survival rates were 49.2% and 85.5% for patients with and without
      serosa invasion, respectively. These findings clearly show that the serosal
      surface, especially in cases of the undifferentiated or infiltrative type of
      gastric cancer, must be closely inspected intraoperatively.

PMID- 7630175
TI  - Completion thyroidectomy for differentiated thyroid carcinoma.
AB  - Completion thyroidectomy is defined as the surgical removal of the remnant
      thyroid tissue following procedures less than total or near-total thyroidectomy.
      The extent of surgical management for differentiated thyroid carcinoma (DTC) is
      controversial. Although some authors advocate subtotal thyroidectomy with lower
      complication rates, total or near-total thyroidectomy and completion
      thyroidectomy have been defended by others because of the improved survival and
      lower morbidity that is comparable with subtotal thyroidectomy. In this study,
      the incidence of residual tumor and surgical complication rates in patients who
      underwent completion thyroidectomy were investigated. The medical records of 165
      patients undergoing completion thyroidectomy for DTC were reviewed. Seventy-seven
      (46.6%) of these patients were found to have residual tumor in the remaining
      thyroid tissue. Anaplastic transformation developed in two of these patients.
      Permanent bilateral recurrent laryngeal nerve palsy occurred in three patients,
      and permanent hypoparathyroidism was seen in one patient. We recommend completion
      thyroidectomy as an efficient and safe method of surgical treatment with a low
      complication rate for DTC.

PMID- 7630176
TI  - Esophageal squamous cell carcinoma occurring in the surface epithelium over a
      benign tumor.
AB  - The coexistence of a benign tumor and carcinoma in the same esophagus is
      uncommon, while the occurrence of carcinoma in the surface epithelium over a
      benign tumor is considered to be extremely rare. Among 587 patients with
      surgically resected esophageal cancer, the cases with carcinoma located over a
      benign tumor of the esophagus were histopathologically investigated and the
      carcinogenesis of such cases was discussed. Only three cases were found to have
      esophageal squamous cell carcinoma located over benign tumors (two were
      leiomyomas and one was a lipoma). All three benign tumors protruded to the
      esophageal surface, and the carcinoma was located just over such tumors without
      coexisting epithelial dysplasia. Moreover, the epithelium, except for portions
      around these tumors, was intact in all three cases. From these findings it was
      suggested that chronic stimulation of the epithelium covering the benign tumors
      might have induced the carcinoma.

PMID- 7630177
TI  - Von Recklinghausen's disease associated with a primary malignant schwannoma of
      the breast.
AB  - A case of a primary malignant schwannoma of the breast is reported. This case and
      the review of the literature illustrate the problems of diagnosing and treating
      this rare malignancy.

PMID- 7630178
TI  - Simultaneous occurrence of medullary carcinoma and papillary carcinoma of the
      thyroid.
AB  - We report a case of simultaneous occurrence of medullary carcinoma and papillary
      carcinoma of the thyroid in the same thyroid gland. Immunoreactivity of
      calcitonin, carcinoembryonic antigen, neuron specific enolase and thyroglobulin
      made a sharp distinction between both neoplasms of the thyroid. It appears
      reasonable to consider that simultaneous occurrence of medullary carcinoma and
      papillary carcinoma of the thyroid in this case does not have embryological or
      genetical significance.

PMID- 7630179
TI  - Modified mastectomy incision for eccentric biopsy sites.

PMID- 7630180
TI  - Interleukin-6 autoantibodies: possible biological and clinical significance.
AB  - The pleiotropic cytokines, interleukin (IL)-1 alpha, type I interferons and IL-6
      also act on cells involved in antibody production. Somehow the immunologic
      tolerance to these cytokines is often spontaneously broken--even in healthy
      individuals. Thus, relatively high concentrations of high affinity IgG antibodies
      against IL-1 alpha and IL-6 frequently occur in the circulation of healthy
      adults. The autoantibodies specifically antagonize the respective cytokines in
      vitro. Thermodynamic estimations strongly suggest that autoimmunity can play a
      significant role in the regulation of certain cytokines. In the light of IL-6
      autoantibodies the possible biological and clinical significance of cytokine
      autoimmunity is discussed.

PMID- 7630181
TI  - Recombinant alpha-2b-interferon in therapy of previously untreated hairy cell
      leukemia: long-term follow-up results of study by Cancer and Leukemia Group B.
AB  - In 1985, Cancer and Leukemia Group B initiated a multi-institutional study to
      define the role of interferon alpha in therapy of previously untreated active
      hairy cell leukemia (HCL). This is a long-term follow-up report of the study.
      Fifty-five evaluable patients were treated with recombinant interferon-2b 2
      million units/m2 subcutaneously three times a week for 1 year. Treatment was well
      tolerated; toxicity mainly consisted of flu-like syndrome and pancytopenia, both
      of a transient nature. Seventy-three percent of patients had objective beneficial
      responses with 8.3 months median time to achieve at least a partial response
      (PR). After 1 year of therapy, the patients have been observed for a median of 5
      years. There was a continual trend towards relapse throughout this period but 28%
      have remained in remission beyond 6 years. Forty-six patients (83%) are alive at
      6 years. Among the 40 patients who achieved at least a PR, there were 28 with
      splenomegaly at the beginning of study: the spleen size was reduced in all with
      interferon alpha therapy and none required splenectomy. This study confirms the
      results of other investigators, and demonstrates that recombinant alpha
      interferon-2b is an effective agent for treatment of hairy cell leukemia.

PMID- 7630182
TI  - All-trans retinoic acid and low-dose cytosine arabinoside for the treatment of
      'poor prognosis' acute myeloid leukemia.
AB  - Thirty-three patients with 'poor prognosis' acute myeloid leukemia, no longer
      suitable for aggressive chemotherapy, were treated with daily oral all-trans
      retinoic acid (45 mg/m2) daily and subcutaneous cytosine arabinoside (20 mg
      standard dose twice a day, day 1 to 10, every 4 weeks). Seventeen patients were
      males and 16 females, the median age was 67 (range 39-82 years). Eleven patients
      were at onset of disease, 15 were refractory to previous conventional therapies,
      three were in first relapse and three in second relapse and one patient had a
      secondary AML. Seventeen patients had a bone marrow blast infiltration < 50% and
      16 > or = 50%. A total of 16 (48%) patients entered complete remission; the rate
      of complete remission increased to 88% in those patients (n = 17) with < 50%
      blast infiltration at the time of entering the study. Seventeen patients (52%)
      were resistant. The difference in response to therapy, according to bone marrow
      blast percentage (< or > or = 50%), was statistically significant (P < 0.001).
      Median duration of complete remission was 34.4 weeks (range 6.4-62.8). Mild to
      moderate hematologic toxicity was the most common side-effect. In conclusion all
      trans retinoic acid and low-dose cytosine arabinoside appears to be an effective
      regimen for inducing complete remission in 'poor prognosis' acute myeloid
      leukemia and patients with < 50% bone marrow infiltration are likely to represent
      the ideal target to receive this combination therapy.

PMID- 7630183
TI  - Carboplatin infusion in relapsed and refractory acute myeloid leukemia--a
      Southwest Oncology Group trial.
AB  - Carboplatin (CBDCA) is an active agent in the treatment of acute leukemia and is
      associated with limited extramedullary toxicity. Simultaneous phase II trials
      were conducted by the Southwest Oncology Group in adult patients with relapsed or
      refractory acute myeloid leukemia (AML). CBDCA was given as a continuous infusion
      at a dose of 300 mg/m2 daily for 5 days. Three (8%) of the 37 eligible patients
      in the relapsed group achieved complete remissions (CRs) lasting 3, 4, and 26
      months. Entry of patients was stopped early in the refractory group due to slow
      accrual and in the relapsed group due to low CR rate. For both groups combined,
      the CR rate was 3/45 or 7% (95% confidence interval 3-18%). There were 12 fatal
      toxicities. Four patients died of intracerebral hemorrhage, three of infection,
      and five of hepatic and/or renal failure. Nonhematologic grade 4 toxicity
      included diarrhea in three patients, hyperbilirubinemia in four, and mucositis
      and renal toxicity in one each. These results suggest that CBDCA should not be
      considered for treatment of relapsed or refractory AML patients with prior high
      dose therapy.

PMID- 7630184
TI  - 2-Chlorodeoxyadenosine (CdA) for patients with previously untreated chronic
      lymphocytic leukemia (CLL).
AB  - The encouraging therapeutic results attained with the purine analogue CdA in
      patients with previously treated CLL prompted us to assess its potential in
      untreated CLL patients. Nineteen patients, 13 males and six females, median age
      65 years (range 27-75), with previously untreated CLL were given monthly courses
      of CdA, 0.12 mg/kg/day as 2-h i.v. infusions for 5 days, until maximum response
      or excessive toxicity. Five patients with Binet's stage A, 10 with stage B and
      four with stage C CLL entered the study. After a median of five courses of CdA
      (range 1-9) nine complete responses (CR = 47%, CI: 24-69%), five partial
      responses (PR = 26%, CI: 7-46%) and five failures (= 26%, CI: 7-46%) were
      recorded. In five complete responders and in one partial responder
      cytofluorometric analysis of blood and/or bone marrow failed to demonstrate a
      residual clonal B cell population. A search for residual disease by PCR
      technology and by immunostaining of bone marrow biopsies however disclosed
      residual leukemic cells in these six cases. Adverse reactions included fever of
      unknown origin (n = 3), pneumonia (n = 2), herpes simplex infection, herpes
      zoster, an anal abscess, a cutaneous rash, autoimmune hemolysis and mental
      disturbance (one patient each). In this small cohort, neither age, stage, blood
      counts, cytogenetics or pattern of bone marrow infiltration at inclusion were
      predictive for response. From these preliminary data, we conclude that CdA has
      remarkable short-term efficacy in patients with previously untreated CLL.
      However, toxicity is not negligible and long-term benefit from therapy with CdA
      still has to be established.

PMID- 7630185
TI  - Waldenstrom's macroglobulinemia with the AML/MDS-associated t(1;3)(p36;q21).
AB  - Two unusual, and perhaps causally related, clinical and cytogenetic features in a
      patient with Waldenstrom's macroglobulinemia are presented. Firstly, during the
      progression of the primary macroglobulinemia bone destruction and hypercalcemia
      occurred. Secondly, a t(1;3)(p36;q21) was found as the sole clonal chromosomal
      abnormality. This translocation is characteristic of acute myeloid leukemia (AML)
      and myelodysplastic syndromes with a high propensity for progressing to AML. The
      t(1;3) has previously never been reported in a lymphoproliferative disorder.
      Since the abnormality is associated with acute transformation of cells of the
      myelopoietic lineages, it is possible that the t(1;3), found in cells of lymphoid
      origin in the present case, not only induced the neoplastic process as such but
      also brought about the unusually malignant tumor progression.

PMID- 7630186
TI  - Immunoglobulin heavy chain class switching, mu to gamma, in a human lymphoma cell
      line FL-318 carrying a t(14;18)(q32;q21) chromosomal translocation.
AB  - Previously, we reported the establishment of a human lymphoma cell line, FL-318,
      carrying a t(14;18)(q32;q21) chromosomal translocation. FL-318 cells had mu-heavy
      chain on the cell surface, while they expressed 'sterile' germ-line gamma
      transcripts, suggesting that the chromatin structure of the immunoglobulin heavy
      chain (IGH) locus was 'accessible' to class switch recombination. After several
      months of in vitro cell culture, we found a small population of FL-318 cells
      expressing the gamma-chain. Using a limiting dilution method, a mu-producing cell
      clone FL-318M, and gamma-producing FL-318G were isolated. Hybridization studies
      with various DNA probes from the IGH locus as well as the BCL2 gene demonstrated
      that the mu-constant gene was deleted on the functional IGH allele of FL-318G
      cells, and that the cells produced abundant productive gamma-chain messages.
      These studies indicated that FL-318 cells underwent spontaneous class switching
      during in vitro cell culture, unrelated to T cell interaction or antigenic
      stimulation.

PMID- 7630187
TI  - Chromosome 17 numerical abnormalities in 55 patients with non-Hodgkin's lymphoma:
      a fluorescence in situ hybridization study.
AB  - Monosomy 17 and structural abnormalities of the short arm of chromosome 17 have
      been reported to influence prognosis and treatment outcome in patients with non
      Hodgkin's lymphoma (NHL). In diffuse large cell lymphoma, these abnormalities
      were associated with refractoriness to chemotherapy, higher proliferative rate
      and poor prognosis. We studied the incidence of chromosome 17 abnormalities in 55
      patients with NHL by using fluorescence in situ hybridization with a directly
      conjugated centromeric probe for chromosome 17. Twenty-three patients (42%) were
      previously untreated. Thirty-four patients (62%) had diffuse large cell lymphoma,
      18 (33%) had follicular low-grade lymphoma, one had small lymphocytic lymphoma,
      one had diffuse mixed cell lymphoma, and one had mantle cell lymphoma. Cells from
      benign lymphoid hyperplasia were used as controls. Eight patients (15%) had
      trisomy 17 in 1.2-40.7% of cells and one patient (1.8%) had monosomy 17 in 68.8%
      of cells. We conclude that monosomy 17 is not common in NHL. Chromosome 17
      deletions should be investigated with region-specific probes to determine their
      clinical relevance in NHL.

PMID- 7630188
TI  - High degree of myeloid differentiation and granulocytosis is associated with
      t(8;21) smoldering leukemia.
AB  - The t(8;21) is a frequent chromosome abnormality in acute myeloid leukemia (AML),
      particularly associated with M2 of the French-American-British (FAB)
      classification, but also found in a few patients with myelodysplastic syndrome
      (MDS). The two genes involved in the t(8;21) have been recently isolated and the
      cDNA of the AML1/ETO fusion gene identified. We have investigated a series of AML
      and MDS patients by a reverse transcriptase-polymerase chain reaction (RT-PCR)
      and analyzed the clinical and laboratory features of leukemia with t(8;21). The
      t(8;21) was only found in a subset of M2, which had the clinical and
      hematological features distinct from those M2 without t(8;21). M2 with t(8;21)
      was associated with a significantly higher myeloid differentiation and with a
      good response to chemotherapy. Moreover, among the patients with refractory
      anemia with excess of blasts in transformation (RAEB-T) the t(8;21) was also
      significantly associated with a higher myeloid differentiation and a good
      response to chemotherapy. M2 patients with t(8;21) could be distinguished on a
      number of hematological parameters, eg white blood cell count and percentage of
      bone marrow myeloblasts and promyelocytes, from RAEB-T carrying the t(8;21).
      Based on these findings we suggest that leukemia patients carrying t(8;21) can be
      grouped into two types; overt acute myeloid leukemia (M2) and smoldering or
      slowly evolving myeloid leukemia.

PMID- 7630189
TI  - Fluorescence in situ hybridization analysis of minute marker chromosomes in
      leukemia with monosomy 7.
AB  - Monosomy 7 was detected in bone marrow cells from three patients, one with
      myeloid leukemia, and two others with myelodysplastic syndrome following previous
      chemotherapy. Fluorescence in situ hybridization (FISH), carried out with an
      alphoid DNA probe specific for chromosome 7 centromere, showed that a small
      marker chromosome present in the tumor cells' karyotype of the three patients,
      was derived from the missing chromosome 7. In two cases, the marker was a ring
      chromosome, whereas in the third case it was a tiny dot-like chromosome,
      unnoticed at first examination on R-banded metaphases. In the three cases, the
      marker was lost in a proportion of tumor cells. FISH experiments suggested that
      the marker centromere had undergone structural alterations, with a fluorescence
      pattern distinct from a normal one. On the whole, these data suggest that:
      firstly, leukemia-associated monosomy 7 results, in a proportion of cases, from a
      structural event rather than from simple loss of a whole chromosome 7; secondly,
      interpretation of interphase FISH must be cautious in monosomy 7 evaluation; and
      thirdly structural alteration of the chromosome 7 derivative alphoid DNA could
      explain its propensity to segregate unequally and to be lost at mitosis.

PMID- 7630190
TI  - Homozygous deletions of the CDKN2 (MTS1/p16ink4) gene in cell lines established
      from children with acute lymphoblastic leukemia.
AB  - Homozygous deletions of the CDKN2 (MTS1/p16ink4) gene have been found at high
      frequency in cell lines derived from a variety of adult solid tumors. In order to
      investigate the status of the CDKN2 gene in cell lines established from childhood
      acute lymphoblastic leukemia (ALL), we surveyed 25 lines representing the major
      pediatric ALL phenotypes for the presence of this gene by Southern blot analysis.
      Homozygous deletions of all or part of the CDKN2 gene were detected in 21 (84%)
      cell lines, including 11 of 14 (79%) early-pre-B-ALL, four of five (80%) pre-B
      ALL, and six of six T-ALL lines. CDN2 mRNA was detected by Northern blotting in
      each of the four lines containing an intact CDKN2 gene. These data suggest an
      important role for CDKN2 deletion in the cause and/or progression of pediatric
      ALL.

PMID- 7630191
TI  - Translocation (11;15)(q23;q14) in three patients with acute non-lymphoblastic
      leukemia (ANLL): clinical, cytogenetic and molecular studies.
AB  - We report on three patients with acute non-lymphoblastic leukemia (ANLL)
      displaying the same chromosomal translocation t(11;15)(q23;q14). The clinical
      course of the disease was aggressive, and survival was short. The FAB subtype was
      M-2 in two cases, and M-1 in the remaining patient. Immunologically two cases
      showed aberrant expression of a lymphoid antigen (CD19 and TdT, respectively).
      HTRX1/MLL gene was rearranged in one patient studied at the time of diagnosis.
      These results plus data scattered in the literature show that the
      t(11;15)(q23;q14) can be added to the list of recurrent rearrangements in ANLL
      involving 11q23.

PMID- 7630192
TI  - Clonal analysis of progenitor cells by interphase cytogenetics in patients with
      acute myeloid leukemia and myelodysplasia.
AB  - Interphase cytogenetics was used to investigate the clonal origin of bone marrow
      (BM) cells, peripheral blood (PB) cells, and in vitro cultured progenitor cells
      of five patients with acute myeloid leukemia (AML) and myelodysplasia (MDS). A
      new in situ hybridization (ISH) technique was used to examine the origin of the
      progenitor cells. Two patients with respectively, trisomy 8 and polyploidy as ISH
      marker were studied both at presentation and during remission. At presentation,
      the in vitro cultured clusters of both cases appeared diploid. Therefore, despite
      the abnormal growth patterns, the cultured progenitors could have been residual
      normal cells. Alternatively, they could have originated from a preleukemic clone
      with a normal karyotype. In both cases abnormal BM and/or PB cells (less than 6%)
      were detected with ISH during remission, indicating partially or completely
      clonal remissions in these patients. Both patients have relapsed. One patient
      with trisomy 10 as ISH marker was analyzed during myelodysplastic phase and after
      progression to AML. On both occasions, abnormally appearing clusters were
      cultured. However, only part of the clusters carried trisomy 10. The presence of
      a subclone characterized by trisomy 10 and an abnormally growing (pre)leukemic
      clone without trisomy 10 may explain this observation. Monosomy 1 and 17 were
      respectively used as ISH markers in two other AML patients. All in vitro cultured
      clusters carried the numerical abnormality. Long-term liquid cultures of these
      leukemias were performed for 10-20 days. In both cases, no residual normal
      clonogenic cells could be detected. Therefore, the selective growth advantage of
      normal progenitor cells in long-term marrow cultures could not be demonstrated in
      these two patients with leukemia. This paper illustrates the usefulness of ISH to
      study the biology of AML at the clonogenic level during preleukemic phase, active
      disease, remission, and under in vitro culture conditions. It is a sensitive
      technique which allows individual analysis of large numbers of small aggregates
      and single cells in culture.

PMID- 7630193
TI  - Distinct apoptotic responses in maturation sensitive and resistant t(15;17) acute
      promyelocytic leukemia NB4 cells. 9-cis retinoic acid induces apoptosis
      independent of maturation and Bcl-2 expression.
AB  - Apoptosis has been investigated in NB4, a t(15;17) human promyelocytic leukemia
      cell line susceptible to maturation by all-trans or 9-cis retinoic acid, and in
      NB4-R1, a subclone resistant to differentiation. Maturation resistant NB4-R1
      cells exhibited an onset of cell death after RA-treatment (72 h), whereas
      maturation responsive NB4 cells showed no such apoptosis, cell death being
      considerably delayed after cell maturation. Only a few NB4-R1 cells underwent
      apoptosis in response to low doses of RA (below 0.1 microM), the surviving cells
      became refractory to higher doses of RA. While these cells became 'resistant' to
      apoptosis they became competent for maturation. Typically, these RA-'primed'
      cells responded to cAMP by maturation, then apoptosis followed rapidly. This
      model furnishes situations where cells are either resistant or susceptible to
      apoptosis, depending on whether they can or cannot undergo maturation. The
      potential role of the Bcl-2 protein in the regulation of apoptosis was analyzed.
      In NB4 and NB4-R1 cell lines, a high expression of the Bcl-2 protein was detected
      by immunocytology and Western blotting. NB4 cells treated with either all-trans
      or 9-cis retinoic acid (1 microM) were induced to differentiate and the level of
      Bcl-2 protein decreased to undetectable levels during terminal maturation when
      only a few apoptotic cells were detected. In NB4-R1 cells, while treatment with
      retinoids does not induce maturation, as much as 64% of cells became apoptotic,
      and immunocytological labelling of NB4-R1 showed a strong cytoplasmic labelling
      of Bcl-2. Although the expression of Bcl-2 remained high, cells were not
      protected from apoptosis. To assess whether Bcl-2 expression could be modulated
      as a consequence of differentiation, NB4-R1 cells previously 'primed' for
      maturation were triggered with cAMP. Downregulation of Bcl-2 protein occurred
      concomitant with maturation, followed by apoptosis. Clearly, NB4 and NB4-R1 cells
      show reciprocal behavior with regards to proliferation, maturation, Bcl-2
      regulation and apoptosis in response to RA. Our results suggest, first, that the
      Bcl-2 downregulation in NB4 cells belongs to the maturation program rather than
      to apoptosis, and second, that neither a high Bcl-2 expression in NB4 cells is
      sufficient to protect cells from 9-cis RA induced apoptosis, nor is its full
      downregulation sufficient to produce apoptosis. Finally, this work suggests that
      apoptosis and maturation programs include events which cannot occur
      simultaneously.

PMID- 7630194
TI  - Particular combinations of signals, by retinoic acid and 1 alpha, 25
      dihydroxyvitamin D3, promote apoptosis of HL60 cells.
AB  - The promyeloid cell line HL60, when grown in serum-free medium, is induced to
      differentiate towards either neutrophils or monocytes by treatment with
      particular concentrations of 9-cis retinoic acid (9-cis RA) and 1 alpha, 25
      dihydroxyvitamin D3 (D3). We have investigated whether treatment of HL60 cells
      with 9-cis RA and D3 can lead to growth arrest and a failure to undergo cell
      differentiation. This occurred in two circumstances and HL60 cells died rapidly
      by apoptosis. First, treatment with 5 x 10(-7) M 9-cis RA and 1.25 x 10(-9)-3.1 x
      10(-10) M D3 promoted growth arrest and apoptosis of HL60 cells. The amount of 9
      cis RA alone promoted significant neutrophil differentiation of HL60 cells. The
      amounts of D3 alone promoted a very low level of monocyte differentiation.
      Treatment with each agent alone did not result in increased levels of apoptosis.
      Second, HL60 cells were treated with concentrations of 9-cis RA (5 x 10(-7) M)
      and D3 (3.9 x 10(-14) M) that were appropriate for induction of neutrophil
      differentiation. At the time when they were undergoing commitment to the
      neutrophil pathway of differentiation (days 1-2), an amount of D3 (1 x 10(-7) M)
      that promotes monocyte differentiation was added to the cultures. HL60 cells
      failed to differentiate and died by apoptosis. Hence, certain combinations of
      signals, elicited by 9-cis RA and D3, promote apoptosis of HL60 cells. This
      finding has important implications for the use of retinoids and D3 in
      differentiation therapy.

PMID- 7630195
TI  - The effects of passive antiviral immunotherapy in AKR mice: I. The susceptibility
      of AKR mice to spontaneous and induced T cell lymphomagenesis.
AB  - The AKR inbred mouse strain displays a high incidence of spontaneous T cell
      lymphomas that arise predominantly in the thymus of 6 to 12-month-old mice.
      Heterogenous nonacute transforming retroviruses are associated with the etiology
      of the disease: the endogenous ecotropic viruses (inherited in AKR mice at two
      non-linked chromosomal loci, Akv-1 and Akv-2), the xenotropic virus and
      recombinant viruses. Prevention of spontaneous T cell lymphomagenesis in AKR mice
      by passive anti-viral immunotherapy was accomplished by suppressing endogenous
      ecotropic virus release. Treatment with monoclonal antibody Hy-72 reacting only
      with Akv1 type ecotropic viruses, or with mAb 18-5 with specificity for both
      ecotropic and MCF recombinant virus envelope glycoprotein (administered from
      birth for 10 days) inhibited similarly T cell lymphoma development. A reduced
      thymus cellularity observed in these mAb treated mice coincided with reduced
      level of earliest intrathymic low CD4 precursor population in their thymus. The
      role of endogenous viruses (MuLV) and presence of potential lymphoma cells (PLCs)
      (identified among bone marrow cells of untreated AKR mice) in enhanced T cell
      lymphomagenesis in AKR mice, triggered by different leukemogenic agents, was
      evaluated. Intrathymic injection of the radiation leukemia virus variant A-RadLV
      or administration of methylnitrosourea resulted in a high lymphoma incidence
      within a short latent period of 80-100 days irrespective of the presence or
      absence of MuLV or PLCs in these treated mice. Thus, a direct action of these
      agents on thymocytes seems to occur. The high susceptibility of untreated AKR
      mice to radiation induced T cell lymphomagenesis was not affected by pretreatment
      with mAb Hy-72; in contrast to markedly reduced sensitivity following
      pretreatment with mAb 18-5 (15 vs 100%). The mAb 18-5 induced resistance to
      radiation lymphomagenesis seems to be related to defects in the bone marrow stem
      cell pool as well as in the thymus microenvironment of mAb 18-5 treated mice.
      Thus, different developmental pathways are involved in enhanced T cell
      lymphomagenesis in AKR mice.

PMID- 7630196
TI  - Serologic and molecular evidence for a possible pathogenetic role of viral
      infection in CD3-negative natural killer-type lymphoproliferative disease of
      granular lymphocytes.
AB  - We studied a series of 18 patients with CD3- lymphoproliferative disease of
      granular lymphocytes (LDGL) for evidence of chronic viral infection, including
      Epstein-Barr (EBV), hepatitis B (HBV), hepatitis C (HCV), human T lymphotropic
      virus (HTLV), and human immunodeficiency virus (HIV). Although all patients
      tested had serologic evidence for past infection with EBV, polymerase chain
      reaction (PCR) analysis of peripheral blood mononuclear cell (PBMC) DNA utilizing
      specific EBV primers demonstrated the presence of EBV-DNA in only six of 17 CD3-
      LDGL cases. A previous history of HBV infection, as defined by the presence of
      circulating IgG anti-HBc antibodies associated with either HBsAg positivity or
      negativity, was documented in seven cases; however, viral DNA was not detected in
      PBMC of these patients using PCR with specific HBV primers. Specific anti-HCV
      antibodies, confirmed by recombinant immunoblot assay, were detected in five CD3-
      LDGL patients; PCR analysis demonstrated the presence of viral RNA in PBMC of two
      of these cases. No patient had antibodies to HTLV-I/II or HIV-1/2. Five patients
      were infected by more than one virus (two with HBV and EBV and three with HBV and
      HCV). Our results provide serologic evidence for past viral infection in the
      large majority of CD3- NK-type LDGL patients. These data suggest that viral
      infection may have played a role early in disease pathogenesis and may no longer
      be necessary in sustaining GL proliferation in CD3- NK-type LDGL.

PMID- 7630197
TI  - Expression of the flt3 receptor and its ligand on hematopoietic cells.
AB  - Expression of the flt3 tyrosine kinase receptor and its ligand were examined on
      various murine and human hematopoietic cell lines. Surface expression of flt3
      receptor and flt3 ligand were detected by flow cytometry using biotinylated human
      flt3 ligand or biotinylated soluble human flt3 receptor Fc fusion protein (flt3R
      Fc), respectively. Flt3 receptor and ligand expression were also examined by
      Northern blot analysis. Flt3 receptor was expressed on the surface of only two of
      nine murine cell lines and nine of 15 human cell lines, with positive cells
      representing the B cell, early myeloid, and monocytic lineages. Staining for
      surface expression of the flt3 ligand revealed that seven of nine murine cell
      lines and nine of 15 human cell lines screened were positive by flow cytometry.
      All murine and human cell lines assayed were positive for flt3 ligand RNA
      expression by Northern blot analysis, but not all cell lines expressing flt3
      ligand mRNA had detectable surface expression. Cells expressing the flt3 ligand
      were of the myeloid, B cell and T cell lineages at various stages of
      differentiation. Only the OCI-AML-5, NALM-6, and AML-193 cell lines coexpressed
      both surface flt3 receptor and ligand. The myeloid leukemic M1 cell terminally
      differentiate into macrophage-like cells under the influence of leukemia
      inhibitory factor (LIF). We found that LIF-stimulated M1 cells down-regulated
      surface expression and mRNA levels of the flt3 receptor, but up-regulated
      expression of the flt3 ligand. Although we could demonstrate that the flt3
      receptor was functional in the M1 cell line, flt3 ligand could not induce the M1
      cells to differentiate.

PMID- 7630198
TI  - Proliferation of MIELIKI a novel t(7;9) early pre-B acute lymphoblastic leukemia
      cell line is inhibited concomitantly by IL-4 and IL-7.
AB  - The present study describes a novel cell line, MIELIKI, established from bone
      marrow of a pediatric patient with B lineage acute lymphoblastic leukemia (ALL)
      at diagnosis. The MIELIKI cell line displays an early pre-B cell phenotype
      (CD10+, CD19+, CD20+, CD34-, Cmu-, sIg-) with rearrangements on both Ig heavy
      chain and k light chain alleles, and carries an unfrequent t(7;9) chromosomal
      translocation identical to the freshly isolated leukemic blasts. The
      proliferation of MIELIKI cells was abrogated by IL-4 and by IL-7, as measured by
      DNA replication and viable cell recovery. The effects of IL-4 and IL-7 were
      mediated, respectively, through the CDw124 and CDw127 IL-4 and IL-7 receptor
      components. Growth inhibition by IL-4 was not mediated by soluble factors
      released by MIELIKI cells in response to IL-4, suggesting the existence of an
      intrinsic negative signaling pathway. Finally, neither IL-4 nor IL-7 were found
      to induce maturation of MIELIKI into cells expressing cytoplasmic or surface
      membrane mu chain. The present cell line should constitute a useful model of
      t(7;9) early pre-B ALL and allow investigation of the relationship between IL-4
      and IL-7 negative signaling in leukemic B cell ontogeny.

PMID- 7630199
TI  - Alterations of cyclin-dependent kinase 4 inhibitor (p16INK4A/MTS1) gene structure
      and expression in acute lymphoblastic leukemias.
AB  - The cyclin-dependent kinase 4 (cdk4) inhibitor (p16INK4/MTS1/CDKN2) gene has been
      recently identified as a putative tumor suppressor gene because of the high
      frequency of homozygous deletion observed in numerous human tumor cell lines,
      including leukemias. However, results obtained from uncultured tumor samples have
      led to discussion of the relevance of these findings. Using reverse transcriptase
      polymerase chain reaction (RT-PCR) and Southern blot analysis, we have
      investigated p16INK4A gene at both RNA and genomic levels in various types of
      leukemias: acute myeloid leukemia (AML) (n = 23); acute lymphocytic leukemia
      (ALL) (n = 22) and B cell chronic lymphoproliferative disorders (CLPD) (n = 33).
      p16INK4A mRNA expression was not found in only 1/20 AML and 2/23 CLPD samples.
      Conversely, p16INK4A mRNA was not detected in 5/17 ALL cases, and intensity of
      PCR products were barely detectable in seven additional cases, possibly related
      to the contamination by normal cells in some cases. By Southern blotting, a
      homozygous deletion of p16INK4A gene was found in 6/17 ALL cases (35%) among
      which 4/6 were negative or weakly positive by RT-PCR assay. None of the five AML
      and 20 CLL samples studied had p16INK4A deletion. Sequence analysis of p16INK4A
      exon 2 did not show point mutation in two of these cases lacking mRNA expression.
      Our data provide further evidence that among hematological malignancies, ALL are
      the most likely to be associated with p16INK4A inactivation, mainly by homozygous
      gene deletion. Since most hematological malignancies-except ALL-are infrequently
      associated with p16INK4A and retinoblastoma (Rb) gene alteration it seems
      worthwhile to explore cdk4 and cdk6 expression to determine whether or not the
      disruption of the p16INK4A/Rb/cdk4/cdk6 regulatory loop might play a role in
      their pathogenesis.

PMID- 7630200
TI  - Evaluation of the impact of allogenic transplant in first remission on an
      unselected population of patients with acute myeloid leukaemia aged 15-55 years.
      The Northern Regional Haematology Group.
AB  - The aim of this study was to collect prospectively unselected, population-based
      data on young adults with acute myeloid leukaemia (AML) over a 9-year period and
      to evaluate the impact on survival of the introduction of allogeneic
      transplantation performed in first remission. The population within the Northern
      Region of England is 3.09 million. During the study period a total of 149 de novo
      patients between 15 and 55 years old presented. The incidence of AML was 0.79 per
      10(5) (age-specific population) in the 15-24-year-old group, 0.85 per 10(5) in
      the group 25-39 years old and 1.35 per 10(5) in the 40-55-year-old group.
      Remission induction success varied with age (74% for patients < 40 years and 58%
      for patients 40-55 years). In the 15-40 year old group 28 patients had an HLA
      matched donor, 22 patients had a transplant (one syngeneic) and 24 patients in
      the 15-40-year-old group in remission at 6 months did not have a transplant. The
      allogeneic group < 40 years old had an event-free survival (EFS) at 4 years of
      62%, whereas patients of the same age who received chemotherapy alone had an EFS
      at 4 years of 24%. A small heterogeneous group of 14 patients who had
      intensification with autotransplant are not included in this analysis. The
      population study approach demonstrates the difficulties of introducing uniform
      treatment strategy in this disease group. The study confirms the view that
      allogeneic transplant in first remission in the 15-40-year-old group is the
      treatment of choice. Unfortunately the overall impact of transplant on the
      population is not great since only 22 of 149 patients (14%) were able to receive
      an allograft in first remission.

PMID- 7630201
TI  - Evidence for a mechanism that can provide both short-term and long-term
      haemopoietic repopulation by a seemingly uniform population of primitive human
      haemopoietic precursor cells.
AB  - One of the controversies surrounding the repopulating capacities of haemopoietic
      stem cells is whether or not the same or different populations are responsible
      for short-term and long-term repopulation after transplantation. To address this
      question, we analysed results obtained from an in vitro model for the clonal
      production of granulocyte-macrophage colony-forming cells (CFU-GM) by individual
      primitive multilineage precursors in adult human bone marrow. The primitive
      precursors adhere to plastic and produce CFU-GM in a 1-week long 'delta' type
      culture. The clones that form are classified as having short maturation pathways
      (clones containing predominantly day 7 CFU-GM) or long maturation pathways
      (clones containing predominantly day 21 CFU-GM). The results indicate that
      individual primitive (P delta) cells produce clones that reach full maturity
      after different periods of time so that cells corresponding to a range of
      maturational stages can become available simultaneously. Consequently,
      transplanted stem cells may be able to provide both rapid and long-term mature
      cell recovery whilst at the same time reconstituting the stem cell pool. These
      results suggest that it might be possible to use highly purified stem cell
      populations, devoid of committed progenitors, for clinical transplantation.

PMID- 7630202
TI  - Myeloperoxidase mRNA detection for lineage determination of leukemic blasts:
      retrospective analysis.
AB  - Myeloperoxidase (MPO) mRNA is an early myeloid marker; its detection in the
      morphologically and immunophenotypically primitive blasts of acute
      undifferentiated leukemia (AUL) establishes myeloid lineage and allows
      reclassification as acute myelogenous leukemia with minimal differentiation (AML
      MO). We have previously reported a procedure for MPO mRNA detection by RT-PCR
      (reverse transcription-polymerase chain reaction) and an adaptation for use of
      routine hematology smears. This variant procedure allows retrospective analysis
      of mRNA and is used in the present study to evaluate the lineage of leukemic
      blasts in seven cases with morphology and cytochemistry consistent with AUL. All
      hematology smears used in this study were air-dried, unstained or Wright-stained
      and stored at room temperature for periods varying between 3 days and 2 years.
      MPO mRNA was detected in six cases, establishing the myeloid lineage of the
      blasts and the diagnosis of AML-MO. In the remaining case, the blasts were MPO
      mRNA negative, confirming the diagnosis of AUL. The RT-PCR procedure for
      retrospective mRNA analysis is useful in the clinical setting, due to its high
      specificity and sensitivity, speed (less than 24 h), safety (no radioactivity)
      and convenient use of routine hematology smears; it is particularly attractive in
      clinical situations when fresh or frozen specimens are no longer available at the
      time when the need for molecular diagnostics becomes apparent.

PMID- 7630203
TI  - Tumor necrosis factor and interleukin-1 synergize with irradiation in expression
      of GM-CSF gene in human fibroblasts.
AB  - Tumor necrosis factor (TNF) and interleukin-1 (IL-1) improve the survival of
      lethally irradiated animals through production of hematopoietic growth factors.
      Exposure of fibroblasts to TNF (1000 U/ml) drastically increased granulocyte
      macrophage colony-stimulating factor (GM-CSF) mRNA at 1 h and the level returned
      nearly to baseline by 24 h. Levels of GM-CSF RNA were less than basal level at 24
      h after exposure to irradiation alone. In contrast, cells cultured with TNF (1 h)
      and then irradiated, had prominent expression of GM-CSF mRNA at 24 h.
      Transcriptional run-on analysis has shown that TNF stimulated the rate of GM-CSF
      transcription by > 10-fold in irradiated cells. Moreover, TNF stabilized GM-CSF
      mRNA at 24 h after irradiation; 4 increased from < 20 min in untreated cells to >
      2 h in cells cultured initially with TNF and followed by irradiation. We repeated
      the same experiments with IL-1 and found that IL-1 had the same effects on
      accumulation, transcription, and stabilization of GM-CSF RNA. Our findings
      indicate that TNF and IL-1 synergize with irradiation in expression of GM-CSF
      gene in human fibroblasts; this increased expression occurs by enhancement of
      transcriptional rate and post-transcriptional stabilization of GM-CSF mRNA.

PMID- 7630204
TI  - Bcl-2 protein expression is not related to short survival in multiple myeloma.
AB  - The oncoprotein bcl-2 can be expressed in malignant plasma cells and might play a
      role in the prevention of corticosteroid-mediated apoptosis, thereby prolonging
      survival of the myeloma cells. We retrospectively investigated whether bcl-2
      expression in bone marrow plasma cells measured by two-color fluorescence for
      immunoglobulin light chains would be related to survival duration in patients
      suffering from multiple myeloma. In all patients the large majority of plasma
      cells expressed bcl-2 (median 91%, range 74-100%). Contrary to our expectations,
      a tendency was observed toward higher percentages bcl-2+ plasma cells in patients
      with a long survival (more than 5 years, n = 9) vs patients who died from
      refractory myeloma within a year of diagnosis (n = 7). This tendency was found
      even when analysis was extended to include four patients in the short diagnosis
      group (n = 11) who had received chemotherapy prior to bone marrow examination.

PMID- 7630205
TI  - A single tube nested RT-PCR for detecting the common myeloid specific chromosomal
      translocations.

PMID- 7630207
TI  - Comment on published paper (Proctor et al, this issue pp 1246-1251)

PMID- 7630206
TI  - ATRA administration in the critically ill patient.

PMID- 7630208
TI  - Early Mayo medical illustrating.

PMID- 7630209
TI  - Bleeding and thromboembolism during anticoagulant therapy: a population-based
      study in Rochester, Minnesota.
AB  - OBJECTIVE: To estimate the incidence of and identify risk factors for hemorrhage
      and thromboembolism during long-term anticoagulant therapy. DESIGN: We conducted
      a population-based retrospective cohort study of all residents of Rochester,
      Minnesota, in whom a course of warfarin therapy intended to last for more than 4
      weeks was initiated between Sept. 1, 1987, and Dec. 31, 1989. METHODS: Medical
      records were reviewed, and pertinent data were compiled. All bleeding
      complications were classified as minor or major on the basis of the bleeding
      severity index, and thromboembolic events were classified as major if they were
      fatal or life-threatening. Cumulative incidences of adverse events were analyzed
      statistically. RESULTS: During the study period, 261 patients had incident
      courses of anticoagulation (52% were male, 61% were 65 years of age or older, and
      31% were 75 years of age or older), with 221 patient-years of warfarin exposure.
      The primary indications for anticoagulation were venous thromboembolism (39%);
      stroke or transient ischemic attack (21%); atrial fibrillation (11%); and
      coronary artery disease, procedures for coronary artery disease, or
      cardiomyopathy (7%). The cumulative incidence of major hemorrhage at 1, 3, 12,
      and 24 months was 1.6%, 3.3%, 5.3%, and 10.6%, respectively, and of major or
      minor thromboembolic events was 2.3%, 5.0%, 7.4%, and 13.1%, respectively. In
      multivariate analysis, (1) a malignant condition was significantly associated
      with major hemorrhage; (2) malignant disease and history of peptic ulcer were
      significantly associated with the combined outcome of major or minor hemorrhage;
      and (3) malignant disease was significantly associated with any thromboembolism.
      Age, sex, atrial fibrillation, history of gastrointestinal hemorrhage, history of
      peptic ulcer, alcohol abuse, hypertension, stroke, and the Charlson comorbidity
      index were not significantly associated with major hemorrhage. CONCLUSION: In
      this population-based study, including a high proportion of elderly patients,
      malignant disease at initiation of warfarin anticoagulation was significantly
      associated with both major hemorrhage and any thromboembolism. Advanced age is
      not a contraindication to anticoagulant therapy.

PMID- 7630210
TI  - Medical and economic costs of psychologic distress in patients with coronary
      artery disease.
AB  - OBJECTIVE: To determine the effect of psychologic distress, measured with a
      commonly used screening questionnaire, on 6-month morbidity and rehospitalization
      costs in coronary patients. DESIGN: Psychologic distress was determined by
      screening with the Symptom Checklist-90--Revised (SCL-90-R) self-report inventory
      during the second week of cardiac rehabilitation. Costs associated with
      cardiovascular rehospitalization during a 6-month follow-up period were recorded,
      and differences between "distressed" and "nondistressed" patients were analyzed
      statistically. MATERIAL AND METHODS: The study cohort consisted of 381 patients
      (311 men and 70 women) referred for cardiac rehabilitation after an index
      hospitalization for unstable angina, myocardial infarction, coronary angioplasty,
      or coronary bypass procedure. Patients with SCL-90-R scores above the 90th
      percentile for outpatient adults were considered distressed (N = 41); patients
      with scores below this level were considered nondistressed (N = 340). RESULTS:
      The 6-month follow-up was complete in all but 1 of the 381 patients. Distressed
      patients had significantly higher rates of cardiovascular rehospitalization, any
      recurrent events, and recurrent "hard events" (cardiac death, myocardial
      infarction, or cardiac arrest and resuscitation) within 6 months after dismissal
      from their index hospitalization in comparison with nondistressed patients.
      Adjustment for other factors associated with a risk of early rehospitalization
      and recurrent events did not reduce the strength or significance of the
      association between psychologic distress and early cardiovascular
      rehospitalization or recurrent events. The mean rehospitalization costs were
      significantly higher in the distressed than in the nondistressed patients ($9,504
      versus $2,146). CONCLUSION: These data add support to the hypothesis that
      psychologic distress adversely affects the prognosis in coronary patients,
      confirm the added morbidity and rehospitalization costs attributable to
      psychologic distress, and suggest the potential for improving the prognosis in
      selected coronary patients by identification and appropriate treatment of
      psychologic distress.

PMID- 7630211
TI  - Hereditary neuropathy with liability to pressure palsies and inherited brachial
      plexus neuropathy--two genetically distinct disorders.
AB  - OBJECTIVE: To determine whether hereditary neuropathy with liability to pressure
      palsies (HNPP) and inherited brachial plexus neuropathy (IBPN) are genetically
      distinct disorders and to evaluate the usefulness of fluorescence in situ
      hybridization (FISH) for diagnosing HNPP in individual patients. DESIGN: We
      studied representative metaphases from patients with HNPP and IBPN with use of
      FISH and a DNA probe. MATERIAL AND METHODS: With use of FISH, 14 persons from 4
      unrelated families with HNPP and 7 members from 3 unrelated families with IBPN
      were studied. We used a DNA probe that hybridizes to chromosome 17p11.2 in an
      area thought to be deleted in HNPP. RESULTS: Each participant in this study who
      had HNPP showed deletion of this chromosome site. Each of the 10 control subjects
      and 7 patients with IBPN showed normal fluorescent signals on both number 17
      chromosomes. CONCLUSION: These results demonstrate that HNPP and IBPN are
      genetically different. FISH with this probe is a sensitive and specific method
      for detecting the chromosomal deletion in individual patients without the use of
      family studies or linkage analysis.

PMID- 7630212
TI  - Pilocytic astrocytomas: well-demarcated magnetic resonance appearance despite
      frequent infiltration histologically.
AB  - OBJECTIVE: To determine the magnetic resonance imaging (MRI) characteristics of
      pilocytic astrocytomas and to correlate them with the histopathologic findings.
      MATERIAL AND METHODS: MRI examinations and histopathologic findings in 56
      patients with pilocytic astrocytomas were retrospectively reviewed. In 38
      patients, findings on MRI were compared with those on computed tomography.
      RESULTS: The tumors occurred at all levels of the central nervous system,
      including the spinal cord. The intracranial tumors were periventricular (73%) or
      periaqueductal (9%). All tumors were typical pilocytic astrocytomas and were
      grade 1 on the basis of the World Health Organization classification. At
      operation, they were often circumscribed and cystic. Radiologically, the tumors
      were well demarcated (96%), had benign morphologic features, and almost always
      showed enhancement (94%). CONCLUSION: MRI of pilocytic astrocytomas typically
      demonstrated a relatively large, sharply demarcated periventricular mass with
      pronounced contrast enhancement but minimal or no associated edema. Often, the
      tumors were cystic on MRI. Despite the well-demarcated appearance grossly and on
      MRI, pathologic review showed that many of these tumors (64%) infiltrated the
      surrounding parenchyma, particularly the white matter.

PMID- 7630213
TI  - In-line skating injuries.
AB  - OBJECTIVE: To assess the type and site of injuries associated with in-line
      skating in patients encountered during an 18-month period. DESIGN: We
      retrospectively reviewed the medical records of patients in our emergency
      department and Sports Medicine Center with injuries that had resulted from in
      line skating between July 1992 and December 1993. MATERIAL AND METHODS: A
      computer search was conducted to identify medical records on which in-line
      skating was denoted as the mechanism of injury. The records were then manually
      reviewed to confirm that the injury had occurred during in-line skating. The
      patient's sex, age, type of injury, and injured body part were recorded. RESULTS:
      During the designated study period, 32 in-line skating injuries were recorded in
      32 patients (19 female and 13 male skaters). The mean age of the study group of
      injured skaters was 17 years (range, 6 to 46). An upper extremity was involved in
      78% of all injuries, and the wrist was the body part most often injured (56%). A
      lower extremity was involved in 16% of all injuries, including two that were
      severe. Of the 32 injuries, 62% were fractures, and surgical treatment was
      necessary for only 1 injury during the study period. CONCLUSION: In this study,
      in-line skating injuries most commonly involved the upper extremities. Fractures,
      particularly of the distal radius, were the most common type of injury. Lower
      extremity trauma was less frequent, but severe injuries can occur. Further
      prospective studies are needed.

PMID- 7630214
TI  - Spells: in search of a cause.
AB  - OBJECTIVE: To determine the cause of spells, present clinical features, and
      discuss diagnostic approaches. DESIGN: Relevant medical literature is reviewed,
      and three illustrative cases are presented. RESULTS: Spells are a sudden onset of
      a symptom or symptoms that are stereotypic, self-limited, and recurrent. A spell
      involves both subjective perceptions and objective findings. In the assessment of
      patients who have spells, use of a systematic approach is important in
      determining the cause. The causes of spells include endocrine, cardiovascular,
      psychologic, pharmacologic, neurologic, and other miscellaneous disorders. A
      comprehensive history, physical examination, and basic laboratory studies are
      important in the initial assessment. Specialized testing is usually needed and
      directed by clinical suspicion based on the spell "phenotype" (for example, a
      pheochromocytoma, carcinoid syndrome, or mast cell disease) and the type of
      facial flush or pallor. CONCLUSION: In the assessment of the patient who has
      spells, the clinician should cast a wide but defensible diagnostic net. Initial
      studies should be directed by the clues obtained from the history and physical
      examination.

PMID- 7630215
TI  - Skin cancers associated with acquired immunodeficiency syndrome.
AB  - OBJECTIVE: To describe the types of skin cancer associated with the acquired
      immunodeficiency syndrome (AIDS). DESIGN: A literature review of AIDS-related
      mucocutaneous neoplasms, including basal cell carcinoma, squamous cell carcinoma,
      bowenoid papulosis and Bowen's disease, squamous cell carcinoma, cloacogenic
      carcinoma, and malignant melanoma, is presented, and the incidence,
      etiopathogenesis, clinicopathologic features, treatment, and prognosis are
      discussed. RESULTS: The association between cutaneous neoplasms and AIDS is well
      known. Neoplasms seem to grow more rapidly and be more invasive in patients with
      AIDS than in other groups of patients. Several oncogenic factors--for example,
      sunlight exposure or human papillomavirus infection--have been associated with
      the development of skin cancer in these patients. The morbidity and mortality
      rates of skin cancer are higher in patients infected with the human
      immunodeficiency virus (HIV) than in the general population. Early and complete
      excision of the neoplasm is especially important. CONCLUSION: A link exists
      between AIDS and the development of skin cancer. HIV-infected patients should be
      followed up vigilantly for early diagnosis of skin cancer. Because these patients
      are less able to suppress common cutaneous malignant disease due to their
      immunocompromised status, biopsy specimens should be obtained from all suspicious
      lesions, and histopathologic assessment should be done.

PMID- 7630216
TI  - Long-term suppressive therapy for Candida parapsilosis-induced prosthetic valve
      endocarditis.
AB  - Prompt valve replacement is advocated in patients in whom candidal prosthetic
      valve endocarditis develops. Unfortunately, some patients with this condition are
      considered nonsurgical candidates, and they are unable to tolerate long-term
      administration of amphotericin B with or without flucytosine. Herein we describe
      a patient with Candida parapsilosis-induced prosthetic valve endocarditis in whom
      oral administration of fluconazole during an 11-month period successfully
      suppressed the fungal infection. Three previously published cases indicate that
      long-term noncurative suppressive therapy for C. parapsilosis-induced prosthetic
      valve endocarditis may allow prolonged symptom-free survival for such patients.

PMID- 7630217
TI  - The Institute of Forensic Medicine established by Dr. Mina Minovici.

PMID- 7630218
TI  - Treatment of alcohol withdrawal in hospitalized patients.
AB  - Alcoholism can be encountered in many aspects of medicine. Frequently, primary
      care physicians are asked to treat patients who are experiencing various stages
      of alcohol withdrawal while hospitalized for intercurrent illness. A thorough
      assessment of the patient is important because the symptoms and signs of alcohol
      withdrawal are nonspecific. Recognizing the patient who is at risk for alcohol
      withdrawal and initiating appropriate treatment can prevent progression to more
      serious symptoms and complications. Benzodiazepines are the drugs of choice for
      pharmacologic treatment of alcohol withdrawal. Their application by means of a
      symptom-triggered approach based on frequent, objective assessment of the patient
      is recommended. Adjunctive therapy for specific complications of alcohol
      withdrawal is discussed. After the acute withdrawal symptoms have been
      controlled, psychiatric or chemical dependence assessment (or both) is strongly
      encouraged.

PMID- 7630219
TI  - Allergy skin testing.

PMID- 7630220
TI  - 45-year-old man with dermatitis and weight loss.

PMID- 7630221
TI  - Pressure ulcers: prevention and management.
AB  - OBJECTIVE: To describe important aspects of pressure ulcer prevention and
      management, especially in elderly patients. DESIGN: We reviewed pertinent
      published material in the medical literature and summarized effective strategies
      in the overall management of the elderly population with pressure ulcers.
      RESULTS: Pressure ulcers are commonly encountered in geriatric patients. The
      development of a pressure ulcer is associated with an increased risk of death.
      Certain well-recognized risk factors, such as immobility and incontinence, may
      predispose to the development of pressure ulcers; consequently, risk factor
      modification is an important aspect of prevention and treatment. For existing
      lesions, various innovative patient support surfaces and wound care products have
      been developed to alleviate pressure and to facilitate wound healing. The use of
      a particular product should be based on the clinical setting and the limited
      scientific evidence available. With treatment, most pressure ulcers eventually
      heal. CONCLUSION: Pressure ulcers are often, but not always, preventable. The
      occurrence of such an ulcer signals the possible presence of chronic comorbid
      disease and should prompt a search for underlying risk factors in patients for
      whom ulcer treatment is considered appropriate.

PMID- 7630222
TI  - Hormone replacement therapy: management of common problems.
AB  - OBJECTIVE: To describe common pitfalls associated with hormone replacement
      therapy (HRT) and recommendations to prevent or ameliorate them. DESIGN: After
      pertinent articles and texts were reviewed, we outlined the available regimens of
      HRT, the commonly encountered side effects, and the management options. RESULTS:
      HRT is frequently prescribed for elderly women. Vaginal bleeding, nausea, breast
      tenderness, migraine headaches, mood alterations, and abdominal bloating are
      common occurrences with HRT. These problems often can be managed by changing the
      dose, using another preparation or regimen, or altering the route of
      administration. For example, transdermal administration of estradiol may be
      tolerated better than oral therapy in patients with nausea. Irregular bleeding
      warrants endometrial biopsy to rule out hyperplasia. CONCLUSION: With simple
      measures, common side effects of HRT can easily be managed by primary-care
      physicians. Gynecologic referral is recommended when endometrial biopsy is
      necessary or when symptoms fail to respond to adjustments in hormone therapy.

PMID- 7630223
TI  - Outcomes of warfarin therapy: lessons from the real world.

PMID- 7630224
TI  - Psychologic factors and course after myocardial infarction: maturing of a risk
      factor.

PMID- 7630225
TI  - Video-assisted thoracic surgery.

PMID- 7630226
TI  - [Fibrinogen and factor VII in women with dyslipidemia. The preliminary results of
      the Bellvitge-Costa de Ponent Study. The Bellvitge Study Group].
AB  - BACKGROUND: The distribution of serum fibrinogen levels and factor VII in a
      population of dyslipemic women and their association with other cardiovascular
      risk factors are herein described. METHODS: Dyslipemic women between 40-70-years
      of age without cardiovascular disease and with no hypolipemic treatment who
      attended 21 primary health care consultations were studied. The following data
      were collected in a questionnaire: smoking habit, high blood pressure, alcohol
      consumption and menopause. The analytical parameters determined were: total
      cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, fibrinogen and
      factor VII. The Pearson correlation coefficient was determined to evaluate the
      association of fibrinogen and factor VII with other cardiovascular risk factors.
      RESULTS: Serum fibrinogen levels correlated positively with LDL-cholesterol and
      with the body mass index and negatively with HDL-cholesterol. Factor VII
      correlated positively with the triglycerides and total cholesterol. No
      significant differences were observed in the hematic factors among the
      hypertensive women and those who were not hypertensive. The same was observed in
      diabetic and in the pre- and postmenopausal women. CONCLUSIONS: In this
      transversal study a relationship was found between serum fibrinogen level and
      factor VII activity and other known cardiovascular risk factors.

PMID- 7630227
TI  - [A descriptive clinical study of a type of arthritis in beekeepers of the Badajoz
      area of La Siberia Extremena].
AB  - BACKGROUND: The appearance of episodes of arthritis has been detected in
      beekeepers in the Siberia Extremadura (Spain) related to working with the hives.
      This present work describes the clinical features of such arthritic syndrome.
      METHODS: Sixty cases were selected at random from a previous epidemiological
      study to undergo a clinical protocol that included, anamnesis, physical signs,
      haematological, biochemical and immunological analyses, and radiological
      exploration of hands, wrists, feet, and pelvis. RESULTS: The picture is
      characterized by episodes of oligoarthritis associated with bee-stings in the
      affected joints or nearby. The most frequent radiologic lesions are pinched
      articular lines, sclerosis, and the presence of geodes. Analytically, there was
      frequent eosinophilia, abnormalities in haemostasis tests, and a rise in serum
      alkaline phosphatase. CONCLUSIONS: An acute inflammatory oligoarthritis of
      unknown cause has been described which affects the hands asymmetrically, and
      which is found in beekeepers in relation to their work with the hives. It
      occasionally involves into a chronic localized arthropathy capable of provoking
      ankylosis and permanent articular disability.

PMID- 7630228
TI  - [The efficacy of the prevaccination detection of anti-HAV in hepatitis A
      vaccination programs].
AB  - BACKGROUND: The convenience of carrying out prevaccination detection studies of
      hepatitis A virus (HAV) markers depends on the relative costs of the detection
      and vaccination, as well as the prevalence of susceptible subjects in each
      population group to be vaccinated. The aim of this study was to analyze the
      efficacy of the systematic prevaccination detection of anti-HAV antibodies in
      Catalonia, Spain. METHODS: The following formula was applied: Unit cost of
      detection + (1-X) x Unit cost of vaccination of anti-HAV negative subjects =
      group vaccination cost, with X being the threshold of prevalence of marker under
      which detection no longer remains efficient. This prevalence was compared with
      the findings of a seroepidemiologic survey carried out in international
      travellers and food handlers. RESULTS: The unit cost of the detection of anti-HAV
      was calculated as 2,733 pesetas, and the unit cost of the vaccination as 9,963
      pesetas obtaining a prevalence anti-HAV threshold of 27%. This prevalence
      corresponds to travellers under the age of 30 years and food handlers under the
      age of 25 years. CONCLUSIONS: The systematic detection of anti-HAV is only
      recommended in population groups in which prevalences higher than 27% may be
      expected. The vaccination is more efficient without a previous marker study under
      this threshold. According to this study, direct vaccination of food handlers
      under the age of 25 years (born after 1969) is recommended as is that of
      international travellers under the age of 30 years (born after 1964). In those
      over the age of these collectives, the prevaccination study is more efficient.

PMID- 7630229
TI  - [HIV without AIDS but no AIDS without HIV].

PMID- 7630230
TI  - [Conflict of interest and clinical research].

PMID- 7630231
TI  - [Progressive external ophthalmoplegia and the Kearns-Sayre syndrome: a clinical
      and molecular study of 6 cases].
AB  - The Kearns-Sayre syndrome (KSS) associates progressive external ophthalmoplegia
      initiating prior to the age of 20 years and pigmentary retinitis with a series of
      other heterogeneous clinical manifestations. The incomplete syndrome is usually
      denominated progressive external ophthalmoplegia (PEO)-plus which is a
      sporadically appearing mitochondrial cytopathy associated with large deletions of
      a variable proportion of mitochondrial DNA (mtDNA) molecules. Six patients with
      PEO-plus/KSS in whom muscle biopsy was performed following a complete clinical
      study are described. The muscle was processed by conventional histochemical
      techniques, electron microscopy, and genetic study (Southern transference,
      polymerase chain reaction, restriction cartography and both manual and automatic
      sequencing). The percentage of mutated mtDNA molecules for each patient was
      obtained by densitometry. The 6 patients presented multiorganic clinical
      manifestations characteristics of most mitochondrial diseases. The presence of
      destructured red fibers were observed in all the biopsies. All the patients
      presented a deletion in the mtDNA of a size between 4,861 to 7,437 base pairs
      (bp). All the deletions appeared flanked by direct repetitions from 4 to 13 bp
      and one also presented inverse repetitions from 5 to 6 bp in the zone next to the
      rupture point. In the 6 cases heteroplasmia was observed with a variable
      percentage of deleted molecules from 23 to 56%. The molecular basis of
      progressive external ophthalmoplegia-plus/Kearns-Sayre syndrome appears to be the
      existence of sole, large deletions in the mitochondrial DNA with the varying in
      location and percentage conditioning the appearance of different phenotypes
      similar among themselves. The 7,437 base pair deletion was the most frequently
      observed in the patients analyzed.

PMID- 7630232
TI  - [Is nitric oxide involved in the pathogenesis of the late complications of
      diabetes mellitus?].

PMID- 7630233
TI  - [Polycythemia and splenomegaly in a 51-year-old woman].

PMID- 7630234
TI  - [Burdened women].

PMID- 7630235
TI  - [Health care according to the sex of patients].

PMID- 7630236
TI  - [The family clinical history. The diagnostic key to the Lynch syndrome].

PMID- 7630237
TI  - [Colonic adenocarcinoma: its presentation as a fever of unknown origin].

PMID- 7630238
TI  - The final autonomy.

PMID- 7630239
TI  - US science on the slide.

PMID- 7630240
TI  - Toxic gas trauma.

PMID- 7630241
TI  - AMA rewrites tobacco history.

PMID- 7630242
TI  - Preventing AIDS: have we lost our way?

PMID- 7630243
TI  - On line for digital mammography.

PMID- 7630244
TI  - Pott's paraplegia today.

PMID- 7630245
TI  - Maximum androgen blockade in advanced prostate cancer: an overview of 22
      randomised trials with 3283 deaths in 5710 patients. Prostate Cancer Trialists'
      Collaborative Group.
AB  - A systematic overview, or meta-analysis, of the randomised evidence on maximum
      androgen blockade (MAB) in advanced prostate cancer identified 25 trials that
      compared conventional castration (surgical or medical) versus MAB (castration
      plus prolonged use of an antiandrogen such as flutamide, cyproterone acetate, or
      nilutamide). Individual patient data were obtained from 22 of the trials. Median
      follow-up was 40 months, during which 57% of patients died (3283/5710). Crude
      mortality rates were 58% for castration alone and 56% for MAB. Life-table
      estimates of the corresponding 5-year survival rates were 22.8% and 26.2%,
      representing a non-significant improvement of 3.5% (95% CI 0-7%). Logrank time-to
      death analyses found no significant heterogeneity between trials (or between the
      effects of different types of MAB) and no significant evidence of additional
      benefit in an overview of all these MAB trial results (2p > 0.1). The currently
      available evidence from randomised trials does not show that MAB results in
      longer survival than conventional castration.

PMID- 7630246
TI  - Manganese and chronic hepatic encephalopathy.
AB  - Clinical observations and animal studies have raised the hypothesis that
      increased concentrations of manganese (Mn) in whole blood might lead to
      accumulation of this metal within the basal ganglia in patients with end-stage
      liver disease. We studied ten patients with liver failure (and ten controls) by
      magnetic resonance imaging (MRI) and measurement of Mn in brain tissue of three
      patients who died of progressive liver failure (and three controls) was also
      done. Whole blood Mn concentrations in patients with liver cirrhosis were
      significantly increased (median 34.4 micrograms/L vs 10.3 micrograms/L in
      controls; p = 0.0004) and pallidal signal intensity indices correlated with blood
      Mn (Rs = 0.8, p = 0.0058). Brain tissue samples reveal highest Mn concentrations
      in the caudate nucleus, followed by the quadrigeminal plate and globus pallidus.
      Mn accumulates within the basal ganglia in liver cirrhosis. Similarities between
      Mn neurotoxicity and chronic hepatic encephalopathy suggest that this metal may
      have a role in the pathogenesis of chronic hepatic encephalopathy. Further
      studies are warranted because the use of chelating agents could prove to be a new
      therapeutic option to prevent or reverse this neuropsychiatric syndrome.

PMID- 7630247
TI  - 3849+10 kb C-->T mutation and disease severity in cystic fibrosis.
AB  - 50% of patients with cystic fibrosis (CF) are homozygous for the delta F508
      mutation, but the remainder have at least one of many other less common
      mutations. The 3849 + 10 kb C-->T splice mutation seems to be associated with
      less severe disease. We report ten CF patients who are hemizygous for this
      mutation. Three male patients do not have azoospermia (sperm counts 12, 53, and
      198 x 10(6)/mL). Another boy died before CF was diagnosed; his genital tract
      appeared normal at necropsy. All patients had clinically sufficient exocrine
      pancreatic function. Pulmonary disease was delayed in onset in most of these
      patients (range < 1 to 16; median 9 years), but then became severe in some,
      progressing to death (in two) and need for transplantation in one. Sweat chloride
      concentration was abnormal (80 mmol/L) in one patient but in others was in the
      intermediate range (45-65 mmol/L). There was substantial variation in pulmonary
      disease severity within sibships. These observations suggest some dissociation in
      genetically determined severity between different organs. There was some evidence
      among these patients of a tendency for disease of the genital tract to become
      progressively more severe. Perhaps sperm banking should be offered to male
      patients. We speculate that some normal CF transmembrane conductance regulator is
      made in patients with this splice abnormality.

PMID- 7630248
TI  - Donors' attitudes towards body donation for dissection.
AB  - We report a survey in the UK of potential whole-body donors for dissection. 218
      people (age range 19-97 years) answered a postal questionnaire, giving
      information about themselves, their reasons for donation, attitudes towards the
      dead body, funeral preferences and medical giving and receiving. In addition to
      altruism, motives included the wish to avoid funeral ceremonies, to avoid waste,
      and in a few cases, to evade the expense of a funeral. 44% understood that their
      bodies would be used as teaching material, 42% for experiments. Whilst 69%
      believed in one or more supernatural phenomena, only 39% said they were
      religious. 69% requested cremation after dissection; 2% wanted to be buried. The
      notion of money incentives to promote donation was overwhelmingly rejected.

PMID- 7630249
TI  - Objective passive-smoking indicators and respiratory morbidity in young children.
AB  - Exposure to environmental tobacco smoke is associated with increased respiratory
      morbidity in young children, but few studies have assessed such exposure
      objectively by urinary cotinine measurements. 501 children aged 1-5 years, a
      random 5% sample of children attending an outpatient clinic, were classified as
      exposed or non-exposed to environmental tobacco smoke with a cut-off of 10 ng
      cotinine per mg creatinine in urine. Exposed children were 3.5 times (95% CI 1.56
      7.90, p < 0.0024) more likely to have increased respiratory morbidity (three or
      more episodes during the previous 12 months) than non-exposed children after
      adjustment for potential confounding factors.

PMID- 7630250
TI  - Association between clozapine response and allelic variation in 5-HT2A receptor
      gene.
AB  - We report allelic association between a polymorphism (T102C) within the coding
      region of the 5-HT2A gene (HTR2A, 13q14-21) and response to clozapine in
      schizophrenic patients. Homozygosity for the C102 allele was more frequent
      (30/57, 53%) among patients who did not respond to clozapine than in those who
      responded (23/92, 25%). This finding is evidence that allelic variation of genes
      which encode neurotransmitter receptors can influence clinical response to
      antipsychotic drugs.

PMID- 7630251
TI  - Raynaud's phenomenon.

PMID- 7630252
TI  - Sarin poisoning in Matsumoto, Japan.
AB  - A presumed terrorist attack with sarin occurred in a residential area of the city
      of Matsumoto, Japan, on June 27, 1994. About 600 residents and rescue staff were
      poisoned; 58 were admitted to hospitals, and 7 died. We examined clinical and
      laboratory findings of 264 people who sought treatment and the results of health
      examinations on 155 residents done 3 weeks after the poisoning. Findings for
      severely poisoned people were decreases in serum cholinesterase,
      acetylcholinesterase in erythrocytes, serum triglyceride, serum potassium and
      chloride; and increases in serum creatine kinase, leucocytes, and ketones in
      urine. Slight fever and epileptiform abnormalities on electroencephalogram were
      present for up to 30 days. Examination revealed no persisting abnormal physical
      findings in any individual. Acetylcholinesterase returned to normal within 3
      months in all people examined. Although subclinical miosis and neuropathy were
      present 30 days after exposure, almost all symptoms of sarin exposure disappeared
      rapidly and left no sequelae in most people.

PMID- 7630254
TI  - Political skies start to brighten for NIH.

PMID- 7630253
TI  - Practising obstetrics and gynaecology in areas with a high prevalence of HIV
      infection.
AB  - What is it like to practise obstetrics and gynaecology in a country with a high
      prevalence of HIV infection? My experience relates especially to Zimbabwe, but
      the same factors apply equally well to Zambia, Zaire, Uganda, Kenya, Tanzania,
      Malawi, and Mozambique. Within a population of 11 million in Zimbabwe, at least 1
      million are HIV positive according to the official figures. AIDS often means
      "home-based care"; the nearest clinic or hospital, which has very little to
      offer, may be 3 hours away by wheelbarrow. Many patients who die with chronic
      diarrhoea lack a piped water supply nearby, an indoor toilet, or even a
      waterproof sheet. Every year in Zimbabwe there are 120,000 confinements of HIV
      positive women compared with 7000 HIV-positive pregnancies in the USA.
      Transmission of the virus in Africa is mainly heterosexual and vertical, although
      blood transfusion still plays a part. Intravenous drug use is not a problem but
      alcohol is, by way of promoting risky behaviour. A secondary epidemic of
      tuberculosis (TB) (also among HIV-negative persons) adds to the difficulties in
      sub-Saharan Africa.

PMID- 7630255
TI  - Insurance reform issue returns to Congress.

PMID- 7630256
TI  - Asbestos: a risk too far?

PMID- 7630257
TI  - Asbestos: a risk too far?

PMID- 7630258
TI  - Asbestos: a risk too far?

PMID- 7630259
TI  - New clinical sign for orthostatic tremor.

PMID- 7630260
TI  - Ciprofloxacin for multiresistant enteric fever in pregnancy.

PMID- 7630261
TI  - Evidence for HIV-1 group O infection in Nigeria.

PMID- 7630262
TI  - Surveillance of heterosexually acquired HIV infection and AIDS.

PMID- 7630263
TI  - Fragile X premutations in familial premature ovarian failure.

PMID- 7630264
TI  - High seroprevalence of Helicobacter pylori infection in coronary heart disease.

PMID- 7630265
TI  - Multiple spontaneous coronary artery dissections in young woman.

PMID- 7630266
TI  - Multiple recurrences and relapse of Streptococcus pneumoniae meningitis.

PMID- 7630267
TI  - A challenge to Lancet readers.

PMID- 7630268
TI  - Evidence-based humanitarian relief interventions.

PMID- 7630269
TI  - Educating the examiner.

PMID- 7630270
TI  - Mortality trends in UK.

PMID- 7630271
TI  - D-lactic acidosis associated with use of medium-chain triglycerides.

PMID- 7630272
TI  - Genetic inheritance of Gilbert's syndrome.

PMID- 7630273
TI  - Duplex ultrasound in diagnosis and monitoring of liver transplant rejection.

PMID- 7630274
TI  - Rheumatoid arthritis.

PMID- 7630275
TI  - SMN gene deletion in variant of infantile spinal muscular atrophy.

PMID- 7630276
TI  - Hepatitis B vaccine in patients on haemodialysis.

PMID- 7630277
TI  - Hepatitis B vaccination of babies in Melanesia.

PMID- 7630278
TI  - Hepatitis B envelope protein mutants.

PMID- 7630279
TI  - Hepatitis B envelope protein mutants.

PMID- 7630280
TI  - Hepatitis C infection and polymyositis.

PMID- 7630281
TI  - Plasmodium falciparum malaria acquired in Berlin, Germany.

PMID- 7630282
TI  - Early detection of Borrelia burgdorferi infection: to treat or not?

PMID- 7630283
TI  - A vaccine for schistosomiasis: there is more.

PMID- 7630284
TI  - Transplantation of non-heart-beating donor kidneys.

PMID- 7630285
TI  - Viruses and primates.

PMID- 7630286
TI  - Intraoral ultrasound evaluation of peritonsillar abscess.
AB  - Peritonsillar cellulitis and peritonsillar abscess are similar clinical entities
      with markedly different methods of treatment. Therefore, accurate diagnosis is
      paramount to appropriate treatment. This pilot study was designed to evaluate the
      sensitivity and specificity of intraoral ultrasound as a noninvasive method of
      differentiating abscess from cellulitis. Sixteen consecutive patients suspected
      of having peritonsillar abscess were prospectively evaluated with intraoral
      ultrasound. The results were confirmed with imaging or surgical drainage. Correct
      diagnoses were made in 9 (90%) of 10 abscesses and in 5 (83%) of 6 cases of
      cellulitis. Our results suggest that, while there is a learning curve for
      intraoral ultrasound, it is an accurate, noninvasive, and inexpensive tool to
      differentiate abscess from cellulitis. We believe that this will be a clinically
      useful technique in the future.

PMID- 7630287
TI  - Orbital osteology: a study of the surgical landmarks.
AB  - This study was conducted to re-examine the osteological anatomy of the orbit.
      Previous studies examined dried human skulls; this study looks at cadaveric
      specimens in a population that more closely resembles the population in the
      United States. Measurements were made of the bony orbit to define safe distances
      for surgical intervention and to identify distances to intraorbital fissures,
      canals, and foramina. Safe distances to the optic nerve were identified by
      subtracting 5 mm from the shortest measured specimen. The safe distances were as
      follows: medial quadrant, 29 mm; inferior quadrant, 39 mm; superior quadrant, 38
      mm; and lateral quadrant, 36 mm. Staying close to the bony wall, not exceeding
      these parameters, and careful identification of anatomical structures should keep
      the surgeon from inadvertent damage to the intraorbital structures.

PMID- 7630288
TI  - Neuroendocrine neoplasms of the larynx.
AB  - Neuroendocrine neoplasms of the larynx are a rare group of tumors that include
      carcinoid tumor, atypical carcinoid tumor, and small cell carcinoma. These
      neoplasms pose interesting diagnostic, prognostic, and therapeutic dilemmas, and
      they are, as a whole, aggressive tumors with a tendency for local and distant
      spread. The authors of this study examined six new cases of laryngeal
      neuroendocrine neoplasms. One case manifested itself as a primary atypical
      carcinoid tumor and caused a "carcinoid syndrome." The remaining five cases were
      small cell carcinomas of the larynx. Histologic, immunocytochemical, DNA flow
      cytometric, and p53 studies were performed on all cases. The expression of neuron
      specific enolase and chromogranin were the most useful markers in this group of
      tumors. Overexpression of p53 protein was present in the majority of cases,
      including the atypical carcinoid tumor. The implications of these studies for
      diagnosis, classification, and treatment are discussed.

PMID- 7630289
TI  - Conservative management of patients with small acoustic tumors.
AB  - Of 432 patients referred for treatment of their cerebellopontine angle tumors, 53
      with acoustic neuromas were managed initially without intervention but with
      adequate follow-up. Mean presenting tumor size in this subgroup of patients was
      0.98 cm (range, 0.2 to 3.0 cm), and average growth rate was 0.16 cm per year.
      Twenty-one patients demonstrated tumor growth with a mean follow-up interval of
      1.9 years. Of these 21 patients, 14 underwent microsurgical excision, 4 received
      radiation, 2 continued to be observed and 1 was lost to follow-up. The remaining
      32 (60%) had no demonstrable growth with a mean follow-up of 2.13 years. Of these
      patients, 29 continue to be followed and 3 were lost to follow-up. Of the
      information evaluated, the only statistically significant relationship is with
      larger tumor size in elderly patients--most likely reflecting the propensity to
      opt for conservative treatment in elderly patients. Tumor growth rate was
      unrelated to presenting tumor size or patient age, which suggests that
      conservative treatment may be appropriate in selected patients.

PMID- 7630290
TI  - Endolymphatic sac tumors: histopathologic confirmation, clinical
      characterization, and implication in von Hippel-Lindau disease.
AB  - The term "endolymphatic sac tumor" (ELST) was coined to identify the likely
      origin of aggressive papillary tumors of the temporal bone. To evaluate the
      validity of this designation, the temporal bone collection at the Massachusetts
      Eye and Ear Infirmary was accessed in an effort to determine the pathologic
      relationship between these tumors and the endolymphatic sac. The search resulted
      in the identification of a de-novo papillary epithelial lesion arising within the
      confines of the endolymphatic sac in a patient with von Hippel-Lindau (VHL)
      disease who harbored a large, destructive ELST in the opposite temporal bone.
      This finding provides the most substantial evidence to date regarding the origin
      of the ELST and the accuracy of its nomenclature. Seven additional clinical cases
      of ELST were identified and analyzed in order to define the natural history of
      these tumors. All patients had a history of sensorineural hearing loss diagnosed
      an average of 10.6 years prior to tumor discovery. The presence of a polypoid
      external auditory canal mass, facial paralysis, and evidence of a destructive
      mass arising on the posterior fossa surface of the temporal bone were common
      physical and radiographic findings. The management of these patients, as well as
      those who are probably prone to such tumors (i.e., VHL patients), is discussed.

PMID- 7630291
TI  - Nervus intermedius function after vestibular schwannoma removal: clinical
      features and pathophysiological mechanisms.
AB  - The results of facial nerve outcome following vestibular schwannoma removal have
      generally ignored the sensory component of the nerve. This lack of reporting
      occurs partly because the distress relating to these functions is less obvious to
      the surgeon, and partly because the facial nerve grading systems currently used
      do not include the functions of the nervus intermedius. We have estimated the
      frequency and nature of abnormalities of nervus intermedius function following
      vestibular schwannoma removal using a retrospective questionnaire. Questionnaires
      were mailed to 257 patients and correctly completed and returned by 224 (87%) of
      the patients. Prior to surgery 5 (2%) of the patients complained of crocodile
      tears, 9 (4%) noted dryness of the eye, and 15 (6%) complained of an abnormality
      of taste. Postoperative crocodile tears occurred in 98 (44%), an absence or
      significant reduction in the production of tears was noted in 162 (72%), and a
      taste abnormality, either a significant reduction or an alteration in character,
      was noted in 107 (48%). The onset of crocodile tears approximated to a bimodal
      distribution, and the recovery of nervus intermedius functions was variable. This
      study has demonstrated that nervus intermedius abnormalities are common following
      vestibular schwannoma removal. It also documents their natural history and
      discusses the underlying pathophysiological mechanisms. We suggest that
      appropriate preoperative counseling be given to all patients undergoing surgery
      and that the functions of the nervus intermedius be included in the surgical
      reporting of facial nerve results in cerebellopontine angle surgery.

PMID- 7630292
TI  - Metastatic basal cell carcinoma of the head and neck.
AB  - Metastases are occasionally associated with cutaneous squamous cell carcinoma but
      only rarely with basal cell carcinoma. There are approximately 200 cases of
      metastases from basal cell carcinoma reported in the world literature. We
      describe 6 additional cases. All of our patients demonstrated recurrence at the
      primary site before they developed their metastases. Metastases presented in
      subcutaneous tissue, cervical lymph nodes, bone, and lung between 1.5 and 14
      years after initial treatment of the primary lesion. The long interval seen in
      these patients between the initial treatment of the primary and the development
      of metastases underscores the need for long-term follow-up in what is often
      thought to be a nonaggressive, nonmetastasizing malignancy.

PMID- 7630293
TI  - Pediatric laryngotracheal reconstruction with cartilage grafts and endotracheal
      tube stenting: the single-stage approach.
AB  - Laryngotracheal reconstruction (LTR) comprises five stages: 1, characterization
      of the stenosis; 2, expansion of the lumen; 3, stabilization of the enlarged
      lumen framework; 4, healing of the surgical site; and 5, decannulation. Single
      stage LTR (SS-LTR) combines and compresses stages 3 through 5 (stabilization,
      healing, and decannulation) into a brief period of postoperative intubation. At
      Children's Hospital Medical Center in Cincinnati, Ohio, from January 1987 to
      December 1993, 116 reconstructive procedures were performed by using
      postoperative intubation. Nine were tracheoplasty or stoma-revision procedures in
      isolation, leaving 107 SS-LTR procedures that included the laryngotracheal
      complex. The use of SS-LTR has increased to 30% of LTRs performed in 1993. Data
      are presented on the success of SS-LTR as measured by the number of
      decannulations and extubations achieved.

PMID- 7630294
TI  - Function preservation in stage III squamous laryngeal carcinoma: results with an
      induction chemotherapy protocol.
AB  - Until recently, standard treatment for stage III laryngeal carcinoma (LC) was
      total laryngectomy and radiotherapy. Recent data suggest that induction
      chemotherapy (ICH) plays a role in preserving function in advanced head and neck
      cancer. No reports to date prospectively evaluate ICH exclusively in stage III
      LC. The authors designed a sequential phase II trial to assess if ICH allowed a
      conservative treatment in this disease. The objective of the first part of the
      study was to rule out a complete response rate with ICH below 30% with P < .05.
      ICH protocol consisted of three courses of cisplatin 100 mg/M2 on day 1 and 5
      fluorouracil 5000 mg/M2 continuous infusion over 120 hours. Radiotherapy was
      administered to patients who attained a complete response (CR). Functional
      surgery (FS) was planned for patients with partial response. A total laryngectomy
      followed by radiotherapy was performed when FS was not feasible. Fifty-two
      previously untreated patients (all males) with squamous stage III LC were
      diagnosed in our institution, and 46 were entered in the ICH trial. After 9
      patients were included, data showed 7 (78%) CR, ruling out a CR rate of less than
      30%. After ICH, a CR was achieved in 29 (63%) of 46 patients. At the end of
      treatment, 35 patients (76%) had a functioning larynx. With a median follow-up of
      3 years, larynx function was preserved in 26 (57%) of 46 patients and in 64% of
      survivors. Four-year actuarial larynx function preservation, overall survival,
      and disease-free survival were 55%, 77%, and 67%, respectively.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7630295
TI  - Incidence, timing, and importance of tracheoesophageal prosthesis resizing for
      successful tracheoesophageal speech production.
AB  - The Blom-Singer method of tracheoesophageal (TE) speech restoration is a proven
      alternative to esophageal and electrolaryngeal speech in patients with total
      laryngectomy. This retrospective study was undertaken to determine the incidence
      and timing of TE prosthesis resizing, amount of change in prosthesis length,
      etiologies associated with resizing, and importance of long-term professional
      follow-up for maintenance of successful TE speech production. Participants were
      26 individuals with total laryngectomy and secondary TE puncture. Results
      indicated that all 18 participants available for long-term follow-up required TE
      prosthesis resizing, and multiple resizings were required in 87% of the routinely
      followed participants. In 14 participants the prostheses were resized shorter
      (sample mean [mean] = -0.7 cm); in 3, longer (mean = +0.5 cm); and in 1, from a
      duckbill to a low-pressure prosthesis of the same size. The mean number of days
      from initial measurement and fitting to first prosthesis resizing was 26. The
      importance of collaboration between the speech-language pathologist and
      otolaryngologist and need for long-term follow-up for successful maintenance of
      TE speech are stressed. Cost containment of rehabilitation services using the
      indwelling TE prosthesis is demonstrated.

PMID- 7630296
TI  - Mucociliary activity and histopathology of sinus mucosa in experimental maxillary
      sinusitis: a comparison of systemic administration of antibiotic and antibiotic
      delivery by polylactic acid polymer.
AB  - To evaluate the efficacy of antibiotic delivered by polyactic acid (PLA) polymer
      in sinusitis, we induced maxillary sinusitis in 32 New Zealand white rabbits by
      occluding the sinus ostium and inoculating the sinus cavity with Streptococcus
      pneumoniae. The rabbits were divided into three groups consisting of group 1
      (control group, 8 rabbits), which was treated only by reopening the ostium; group
      2, which was treated by both reopening the ostium and injecting ampicillin
      intramuscularly (40 mg/kg/day in three divided doses, 12 rabbits); and group 3
      (12 rabbits) in which a piece of PLA-polymer ampicillin (0.326 mg) sheet (1.5 x
      1.5 cm) was placed within the sinus after re-establishing ostial patency. The
      light microscopic findings such as epithelial ulceration, loss of cilia,
      infiltration of inflammatory cells, and edema were less pronounced in group 2 and
      minimal in group 3. The electron microscopic findings such as swelling of
      mitochondria and endoplasmic reticulum and protruded cytoplasm were severest in
      the control group, followed by groups 2 and 3. The mucociliary transport speed
      measured at the medial wall of the maxillary sinus was highest in group 3. The
      results of this study suggest that treatment with PLA-polymer ampicillin may have
      a better efficacy in maxillary sinusitis than that with systemic administration
      of ampicillin.

PMID- 7630297
TI  - Shortcomings of lateral sinus radiograph in the preoperative determination of the
      extent of endonasal endoscopic sinus surgery.
AB  - Lateral sinus radiograph is helpful in determining the distances between certain
      anatomic landmarks in preparation for endonasal endoscopic sinus surgery.
      However, some misleading factors limit the usefulness of this radiograph. In this
      study these distances were measured in 49 patients and compared with measurements
      obtained from another imaging modality, magnetic resonance imaging, which
      provides more accurate measurements. Results show a discrepancy in the
      measurements of distances between some of these landmarks that cannot be
      explained by the factor of magnification alone on the sinus radiographs.
      Statistical analysis of the results for women revealed a significant discrepancy
      between the distances from the nasal spine to the midfovea ethmoidalis, the
      sphenoethmoid junction, and the posterior sphenoid wall as measured on MR images
      and those as measured on lateral sinus radiographs (P < .05). For men the same
      was true for the distances from the nasal spine to the midfovea ethmoidalis and
      the posterior sphenoid wall (P < .05). It is concluded that there should be
      reservations in the surgical application of data provided by the lateral sinus
      radiograph before endoscopic sinus surgery.

PMID- 7630298
TI  - Transnasal endoscopic medial maxillectomy in inverted papilloma.
AB  - This study comprised 17 cases of inverted papilloma, which were divided into two
      groups. The first group included 8 cases that lacked maxillary sinus involvement.
      They were subjected to intranasal endoscopic resection with safety margin. The
      second group included 9 cases involving the maxillary sinus with or without nasal
      extension. They were subjected to transnasal endoscopic medial maxillectomy.
      Follow-up for an average of 43 months in group 1 and 28 months in group 2
      (excluding the 5 cases with less than 2 years of follow-up) showed no recurrence.
      The author realized that inverted papilloma can be divided into two groups from
      the anatomic and behavioral points of view and accordingly should be managed
      differently. For those lesions without involvement of the maxillary sinus,
      intranasal endoscopic resection is effective; for those lesions with maxillary
      sinus involvement, transnasal medial maxillectomy, which could be performed
      safely under endoscopic control, is recommended.

PMID- 7630299
TI  - Rhinoscleroma treated with ciprofloxacin: a case report.
AB  - Rhinoscleroma, a chronic progressive infection of the nose and associated
      structures caused by Klebsiella rhinoscleromatis, has posed a therapeutic dilemma
      since its identification in the late 1800s. Although a number of antibiotics have
      been found to be effective in this relapsing disorder, the lengthy duration of
      treatment can lead to problems with adverse effects and compliance, especially
      with the traditional therapies of streptomycin and tetracycline. We report on a
      patient with extensive nasal rhinoscleroma who achieved pathologic and
      bacteriologic resolution during treatment with oral ciprofloxacin after previous
      courses of tetracycline and trimethoprim-sulfamethoxazole. Ciprofloxacin may
      prove to be useful in the therapy of rhinoscleroma because it is convenient for
      oral administration, achieves good tissue levels, is concentrated in macrophages,
      and is generally well tolerated as long-term therapy. As mentioned in a recent
      review of patients with rhinoscleroma at the Mayo Clinic, the fluoroquinolones
      deserve further study as potentially highly effective agents for this uncommon
      but significant infectious condition.

PMID- 7630300
TI  - The effect of antihistamines on the laryngeal chemoreflex.
AB  - The laryngeal chemoreflex (LCR) consists of apnea, laryngospasm, and
      cardiovascular changes in neonates after laryngeal irritation and has been
      implicated in sudden infant death syndrome and apnea of infancy. Antihistamines
      attenuate a similar vagally mediated pulmonary chemoreflex. The intravenous
      antihistamine effect on the LCR was studied in neonatal piglets. Laryngeal muscle
      activity, respiration, blood pressure, and pulse were measured during water
      stimulation of the LCR. After baseline LCR recordings, intravenous
      diphenhydramine (2.5 mg/kg) or cimetidine (20 mg/kg) was bolused (control group
      received saline). LCR measurements were repeated over 7 hours. Diphenhydramine
      significantly shorted apneas (P < .05) 3 to 7 hours after drug bolus, which is
      believed to be secondary to central atropinic effects. Cimetidine demonstrated no
      attenuation of the LCR.

PMID- 7630301
TI  - Chemosensory function and diet in HIV-infected patients.
AB  - Alterations of chemosensory function have been noted in human immunodeficiency
      virus (HIV)-infected patients, but their frequency, severity, and relationship to
      diet have not been adequately assessed. Odor and taste identification tests and a
      taste-intensity scaling task were administered to 25 men who were HIV-infected
      but otherwise healthy. Responses were compared to those of 49 comparably aged
      male control subjects. Dietary information was obtained by questionnaire.
      Although 72% of HIV-infected patients reported some chemosensory alteration, no
      significant differences in taste identification ability or intensity ratings were
      observed between patients and controls. Twelve percent of patients had poor odor
      identification scores, but the group mean was similar to that of controls.
      Neither measured nor self-reported sensory indices were significantly related to
      any variable of health (e.g., HIV helper cell (CD4) count, body weight, or body
      composition), treatment, or diet.

PMID- 7630302
TI  - The effect of photodynamic therapy on the mechanical integrity of normal rabbit
      carotid arteries.
AB  - Photodynamic therapy (PDT) for tumor ablation is effective in the treatment of
      superficial cancers. Adjunctive intraoperative PDT has been proposed for the
      "sterilization" of tumor beds after the resection of malignancies. Arteries in
      photosensitized animal models exposed to appropriate light receive characteristic
      injury. This study was conducted to determine whether photodynamic injury to the
      rabbit carotid artery results in thrombotic occlusion or weakening of the vessel
      wall. PDT of the carotid arteries of New Zealand white rabbits, using either
      disulphonated aluminum phthalocyanine or 5-aminolevulinic-acid-induced
      protoporphyrin IX as the photosensitizer, was performed with a light dose of 100
      J/cm2. Histologic examination of the carotids treated with either agent
      demonstrated typical full-thickness loss of cellularity 3 days after PDT. All
      vessels remained patent, and no inflammatory infiltrate was evident. Elastin van
      Gieson staining showed preservation of inner and medial elastic laminae and
      medial and adventitial collagen. Additional rabbits were similarly treated with
      PDT to 1-cm segments of both common carotid arteries. The animals were sacrificed
      at 3, 7, and 21 days. The carotids were exposed, and both control and treated
      segments were subjected to intraluminal hydrostatic distention until the vessels
      burst. No reduction in the pressure required to burst the vessels was evident in
      the treated vessels as compared with the control vessels. The authors of the
      study concluded that despite full-thickness cell death, PDT-treated arteries are
      not at risk for thrombotic occlusion or hemorrhage.

PMID- 7630303
TI  - Maintenance of temporal fossa contour following anterolateral skull base surgery.

PMID- 7630304
TI  - GORE-TEX graft midfacial suspension and upper eyelid gold-weight implantation in
      rehabilitation of the paralyzed face.

PMID- 7630305
TI  - Lower lip splitting incisions: anatomic considerations.

PMID- 7630306
TI  - Directory of Otolaryngological Societies.

PMID- 7630307
TI  - A model for predicting transfusion requirements in head and neck surgery.
AB  - INTRODUCTION: Although allogeneic blood transfusions have allowed surgeons
      increased latitude in resecting advanced cancers, they can cause significant
      morbidity or even death in rare instances. Potential side effects may include
      transmission of infection and immunosuppression leading to an increased risk of
      cancer recurrence. Because patients have become more reluctant to receive
      transfusions, they frequently request preoperative autologous blood donation
      (PABD). In practice, however, only 50% or less of the donated blood is ultimately
      transfused while the remainder is discarded. PURPOSE: The purpose of this study
      was to develop a transfusion prediction and risk assessment (TPRA) model for
      predicting the need for perioperative blood transfusions in patients undergoing
      major head and neck oncologic surgical procedures. By knowing the probability for
      blood transfusion, the physician and patient can make an educated decision
      regarding the need for PABD. PATIENTS AND METHODS: Over a 4-year period, 436
      patients underwent major head and neck surgical procedures for neoplasms of the
      upper aerodigestive tract, the thyroid gland, and the salivary glands. Data
      obtained prospectively on each patient included age and gender, the TNM stage,
      primary disease site, type of prior treatment, estimated intraoperative blood
      loss, duration of surgery, transfusion requirements, preoperative and
      postoperative hemoglobin and hematocrit levels, type of procedure and method of
      reconstruction. These variables were examined singly and in combination both for
      descriptive purposes and to evaluate their interrelationships. In order to
      develop the TPRA model, only the 12 variables available prior to the surgical
      procedure were examined. Variables associated with transfusion need were
      evaluated further in a multivariate analysis. The logistic regression model
      allowed a linear expression of patient characteristics to be related to a
      function of the probability of transfusion need. Analyses of association between
      categorical variables and transfusion status were based on chi-squared, Fisher's
      Exact, and Mann-Whitney U tests. RESULTS: Overall, 51 (11.7%) patients required
      blood transfusions. The median number of units transfused was 2.0 (range, 1 to 13
      U). Univariate analysis demonstrated a higher probability for blood replacement
      in patients with oropharyngeal or hypopharyngeal primary tumor sites, a
      preoperative hemoglobin level below normal, prior chemotherapy, composite
      resection, flap reconstruction, between 50 and 59 years of age, and T3 or T4
      tumor stage. Logistic regression analysis demonstrated that the need for flap
      reconstruction, a preoperative hemoglobin below the normal level, and T3 or T4
      primary stage were the three factors most significantly associated with the need
      for transfusion (P < .03). Based on eight combinations of these three variables,
      transfusion risk predictions were obtained. The TPRA model predicted that
      patients with a normal hemoglobin level who did not require flap reconstruction
      and did not have either a T3 or T4 primary stage tumor had the lowest probability
      (.02) for requiring blood transfusion. Patients at highest risk (.65) were those
      with less than a normal hemoglobin level, who required flap reconstruction, and
      had T3 or T4 primary tumor stage. Based on the TPRA model, an algorithm was
      developed which could serve as a guideline for preoperative transfusion planning.
      CONCLUSION: By using the TPRA model to change guidelines for preoperative
      transfusion planning, costs can theoretically be reduced by 50% without
      significantly increasing the risk of exposing patients to allogeneic blood
      transfusion. If the TPRA model proves accurate in a follow-up study to test its
      validity, it may have clinical utility for aiding the surgeon in more cost
      effective transfusion planning.

PMID- 7630308
TI  - Harris P. Mosher Award thesis. Peritonsillar abscess: incidence, current
      management practices, and a proposal for treatment guidelines.
AB  - Currently there is no agreement on the treatment of patients who develop a
      peritonsillar abscess (PTA). This lack of consensus results in highly variable
      and possibly expensive therapeutic regimens that may not provide optimum quality
      patient care at reasonable cost. The present study evaluates surgical, medical,
      diagnostic, and cost factors that affect the management of PTA based on the
      following: 1. a cohort study of 123 patients with PTA treated using needle
      aspiration as the initial surgical drainage; 2. a national survey of the PTA
      management practices of otolaryngologists; and 3. meta-analyses of various
      components of the treatment regimen for PTA. In the cohort study, patients
      diagnosed with PTA were treated by both otolaryngologists and emergency medicine
      specialists with needle aspiration as the primary surgical modality resulting in
      a 96% acute resolution rate for PTA. In the national survey, questionnaires were
      sent to 2000 randomly selected members of the American Academy of Otolaryngology
      Head and Neck Surgery regarding their management of PTA. The return rate was 73%.
      Ninety-six percent of the physicians who returned survey forms treated an average
      of seven PTAs per year using either needle aspiration, incision and drainage, or
      abscess tonsillectomy to drain the abscess initially. The incidence of PTA in the
      United States and Puerto Rico among patients 5 to 59 years of age treated by
      survey practitioners is 30.1 per 100,000 person years, accounting for
      approximately 45,000 cases per year. Four meta-analyses were completed to
      quantify the success rate of needle aspiration in the treatment of PTA (94%), the
      recurrence rate of PTA (10% to 15%), the rate at which penicillin-resistant
      microorganisms are found in patients with PTA (0% to 56%), and the rate of prior
      oropharyngeal infections associated with PTA (11% to 56%). The recurrence rate
      for PTA in the United States is 10%, which is significantly different from the
      recurrence rate of 15% reported from the rest of the world (P < .002). A clinical
      intervention for PTA is proposed based on the clinical series, the national
      survey data, and the meta-analyses. These clinical guidelines recommend that
      needle aspiration be used as the initial surgical drainage procedure for all
      patients with a PTA other than those who have indications for abscess
      tonsillectomy. Patients should be treated in an outpatient setting, should
      receive penicillin if they are not allergic to it, and should receive adequate
      pain medication. The evidence does not suggest that there is any benefit in
      examining the abscess contents for microorganisms. Approximately 30% of patients
      with PTA can be expected to exhibit relative indications for a
      tonsillectomy.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7630309
TI  - Acute tyrosine depletion reduces tyrosine hydroxylation rate in rat central
      nervous system.
AB  - An amino acid cocktail was devised that would rapidly reduce central nervous
      system (CNS) tyrosine levels in rats following gastric intubation. The effect of
      this treatment on in vivo tyrosine hydroxylation rate was examined. Serum
      tyrosine (TYR) levels, the serum ratio of TYR to the sum of its transport
      competitors, and CNS TYR concentrations fell substantially within 60 minutes of
      intubation and remained low for at least 3 hr. In vivo tyrosine hydroxylation
      rate, evaluated in hypothalamus and retina 2 hr after amino acid intubation, also
      declined significantly. The results suggest that an amino acid mixture can be
      devised that will cause an acute reduction in TYR levels and hydroxylation rate
      in rat CNS. This procedure may ultimately prove applicable to humans to examine
      functional consequences in particular CNS regions of reducing neuronal
      catecholamine synthesis.

PMID- 7630310
TI  - Ventromedial hypothalamic lesions induce the proliferation of gastrointestinal
      mucosal cells in the rat.
AB  - We reported recently that ventromedial hypothalamic (VMH) lesions increased the
      synthesis of DNA in the gastrointestinal tract of rats by the firing of vagus
      nerve activity, mainly via cholinergic receptor mechanisms. In the present study,
      we examined whether the mitotic response is due to proliferation of a cell
      population--mucosal, submucosal, or muscular layer. A monoclonal antibody to
      proliferating cell nuclear antigen (PCNA) has previously been shown to be capable
      of identifying proliferating cells. Samples of formalin-fixed gastrointestinal
      epithelium, taken before and after VMH lesioning, were immunostained with the
      anti-PCNA monoclonal antibody, and the labeling index (LI) was determined. To
      discriminate the effect of hyperphagia in VMH lesioned rats, we utilized the
      method of pair-feeding. Cell proliferation was examined by the PCNA-labeling
      technique 0, 1, 3, and 7 days after VMH lesioning. The increase in proliferation
      was confined to cells in the mucosa and did not involve the muscularis and
      serosa. Studies in control animals showed that the LI was higher in the small
      intestine than in other gut segments, and higher in the large intestine than in
      the stomach. The mean PCNA-LI began to increase at 1 day and continued to
      increase for 3 days, then decreased 7 days following the lesioning. Results
      indicate that the gastrointestinal mucosa is in a state of hyperproliferation
      after VMH lesioning.

PMID- 7630311
TI  - Effects of sex hormones on the steroidogenic activity of dispersed adrenocortical
      cells of the rat adrenal cortex.
AB  - The effect of 17 beta-estradiol and testosterone on glucocorticoid secretion were
      studied in vitro by using dispersed inner adrenocortical cells obtained from
      gonadectomized female and male rats. Independently of the sex of animals,
      estradiol enhanced basal, but not ACTH-stimulated corticosterone (B) secretion;
      conversely, testosterone inhibited ACTH-stimulated, but not basal B output. HPLC
      analysis of steroid secreted demonstrated that estradiol induced comparable rises
      (53-62%) in basal pregnenolone (PREG) and total post-PREG secretion
      (progesterone, 11-deoxycorticosterone and B). Testosterone inhibited by about 30%
      ACTH-stimulated PREG production and by about 54% total post-PREG secretion (B was
      decreased to 56% of the control value, and other steroid hormones were below the
      limit of sensitivity of our assay system). These findings indicate that sex
      hormones directly affect rat adrenocortical secretion, mainly by acting on the
      rate-limiting step of steroidogenesis (i.e. the conversion of cholesterol to
      PREG); moreover, they suggest that testosterone is also able depress the activity
      of the enzymes operating distally to cholesterol side-chain cleavage.

PMID- 7630312
TI  - Epididymal fat depot lipoprotein lipase activity is lower in animals with high
      endogenous fat preferences.
AB  - Adipose tissue lipoprotein lipase (LPL) is a key enzyme responsible for the
      clearance of circulating triglycerides and has been linked to certain pathologic
      states such as obesity. In order to investigate whether an animal's endogenous
      fat-preference is associated with differences in adipose tissue LPL, we measured
      enzyme activity in epididymal fat from high- and low-fat preferring rats.
      Utilizing a 24h ad libitum feeding paradigm, four groups of outbred adult male
      Sprague-Dawley rats were screened separately for their macronutrient preferences.
      Animals exhibiting high- or low-fat preferences were identified and placed back
      on standard chow. LPL activity was measured in epididymal fat under chow fed or
      fasted conditions. Epididymal fat LPL activity was significantly less in the high
      fat-preferring animals relative to the low-fat-preferring, in both the standard
      chow-fed state (p = 0.014) and fasted (p = 0.0007) state. LPL activity in heart
      ventricle and brown adipose tissue was also measured from the same animals.
      Activity in heart ventricle and brown adipose tissue was significantly lower in
      the high-fat-preferring group as compared with the low-fat-preferring only
      following a 24h fast (p = 0.0012 for heart and p = 0.0085 for brown adipose, high
      versus low-fat preferring). The data indicate that differences in tissue LPL
      activity exist between animals with inherent differences in fat preference.
      Future comparative studies between the two groups of fat-preferring animals could
      lead to important clues to the regulation of the LPL.

PMID- 7630314
TI  - Extracellular and intracellular effects of polyamines on smooth muscle
      contractions.
AB  - The natural polyamines spermine, spermidine and putrescine, and their metabolic
      products N1-acetylspermine (N-AS) and 5'-deoxi-5'-methyl-thioadenosine (DMT), but
      not N1-acetylspermidine nor N-acetylputrescine, relax the KCl-induced contraction
      in rat uterus in a dose-dependent way. This relaxing effect is counteracted by
      CaCl2 (0.1-6 mM) but not by Bay K 8644. Spermine, N-AS and DMT also inhibit the
      contraction induced by methacholine and PGF2 alpha. Spermine, DMT and N-AS relax
      the vanadate-induced contraction in uterus incubated in calcium-free solution
      plus EDTA. However, in the vanadate contraction, the EC50s are higher than those
      obtained with other contracturants. These results suggest that polyamines inhibit
      smooth muscle contraction by action at plasma membrane level decreasing the
      influx of calcium. However, intracellular actions of polyamines could also be
      involved in their effects.

PMID- 7630313
TI  - Inhibition of angiotensin II-stimulated inositol phosphate production by D2
      dopamine receptor is calcium-dependent in human trophoblastic cells.
AB  - We previously reported that dopamine (DA) acted via D2-dopamine receptors in
      human trophoblastic cells to inhibit All-stimulated inositol phosphate (InsP)
      accumulation. However, the mechanism by which DA inhibited All-stimulated InsP
      accumulation is still unknown except that this inhibitory effect was sensitive to
      Pertussis toxin (PTX). In this study, we characterize this DA-mediated inhibition
      of All-stimulated InsP production in human placenta. Freshly isolated human term
      placental cells were prelabeled with myo-[2-3H]inositol and incubated with
      various stimuli in the presence of 10 mM LiCl. All (10(-6) M) stimulated 1.5
      times the human trophoblastic cell InsP production whereas DA (10(-4) M)
      inhibited this All-stimulated InsP production by 54 +/- 7%. This inhibitory
      effect was mimicked by bromocriptine (53 +/- 3% of inhibition), a D2-dopamine
      agonist. We recently reported that bromocriptine inhibited human placental
      adenosine 3',5'-cyclic monophosphate (cAMP) production. Increasing the
      intracellular concentration of cAMP levels by adding forskolin did not modify the
      effect of DA and bromocriptine on InsP accumulation. On the other hand, the
      effect of DA and bromocriptine on All-stimulated InsP production were greatly
      affected by treatments that modify the cytosolic free Ca2+ concentration.
      Specifically, the D2-dopaminergic mediated inhibition was prevented by treatment
      of cells with the Ca2+ ionophore ionomycin (10(-5) M) and was mimicked either by
      removal of Ca2+ from incubation medium (53 +/- 6%) or by blockage of voltage
      gated Ca2+ channels with nifedipine (51 +/- 7%). Our data indicate that the
      inhibitory effect of D2-dopamine agonists on All-stimulated InsP production is an
      indirect event probably due to the DA-inhibition of calcium influx.

PMID- 7630315
TI  - The relaxant action of jatrophone in rat portal vein. A comparison with protein
      kinase C inhibitors.
AB  - Jatrophone, staurosporine and H-7, caused graded inhibition of rat portal vein
      contractions induced by phorbol 12-myristate 13-acetate (PMA), noradrenaline,
      endothelin-1 or KCl, with IC50s of 86 nM, 13 microM, 11 microM and 9 microM,
      respectively. Jatrophone was equipotent to H-7, but 100 to 500 fold less potent
      than staurosporine. Jatrophone, H-7 and staurosporine, also dose-dependently
      inhibited rhythmic contractions of the rat portal-mesenteric vein with IC50s of
      15 microM, 9 microM and 75 nM, respectively. Jatrophone, H-7 and staurosporine
      caused graded relaxations of preparations contracted with endothelin-1 or PMA
      with IC50s of 12 and > 1000 microM, 8 and 13 microM and 7 and 12 nM,
      respectively. All three compounds caused graded inhibition of caffeine-induced
      contractions in Ca(2+)-free solution containing EGTA. The similarity between the
      vasorelaxant actions of jatrophone, staurosporine and H-7 in rat portal vein
      suggests that jatrophone acts, at least in part, through inhibition of PKC
      dependent mechanisms. Moreover, like the PKC inhibitors, its vasorelaxant action
      may also involve other mechanisms unrelated to protein kinase C inhibition.

PMID- 7630316
TI  - Chromatographic evidence for Amadori product formation in rat liver
      aminophospholipids.
AB  - This work presents data which indicates the presence of Amadori product derived
      from Maillard reaction in aminophospholipids. The presence of 5-HMF, a stable
      derivative of acid-treated Amadori product, in the phospholipidic fraction from
      cell membranes was established by HPLC-UV and subsequent GC/MS analysis. The
      assay for 5-HMF in rat liver phospholipid revealed the presence of this molecule
      in membrane phospholipids of euglycemic rats, and showed increased glycation
      levels in membrane phospholipids from streptozotocin-induced diabetic rats (p <
      0.001). This gives a new insight to cell membrane physiology and physiopathology.

PMID- 7630317
TI  - 2',3'-Dideoxycytidine induced drug resistance in human cells.
AB  - 2',3'-Dideoxycytidine (ddC) is a nucleoside analogue that inhibits HIV-1
      replication in vitro and is currently used in AIDS therapy. This compound exerts
      a delayed cytotoxicity due to inhibition of mitochondrial DNA (mDNA) synthesis.
      We have found that long term exposure of U937 human monoblastoid cells to ddC
      allowed the selection of a drug-resistant cell line (U937-R) with 66% mDNA,
      normal ddC transport and altered deoxycytidine kinase kinetic properties. In this
      paper we show that U937-R cells contain an increased number of mitochondria per
      cell and a reduced copy number of mDNA/mitochondria. Furthermore, the
      intracellular concentrations of deoxycytidine 5'-triphosphate (dCTP) and 2',3'
      dideoxycytidine 5'-triphosphate (ddCTP) are also reduced although with a higher
      dCTP/ddCTP ratio in U937-R compared to the parental cells. This mechanism of drug
      resistance, with drug-resistance based on viral mutations, can provide an
      explanation for drug failure in antiviral therapy.

PMID- 7630318
TI  - Comparison of chromogranin A and pancreastatin levels in plasma of patients with
      pancreatic islet cell tumor.
AB  - The plasma levels of chromogranin A (CGA) in patients with islet cell tumor and
      plasma CGA responses to administration of a somatostatin analogue (Octreotide) in
      two of these patients were examined in comparison with plasma pancreastatin (PST)
      levels. There was a significant correlation between the fasting plasma levels of
      CGA and PST (r = 0.6, P < 0.001). Administration of the somatostatin analogue
      reduced the plasma concentrations of PST and CGA within 1 h, but the responses of
      CGA and PST to the analogue were not parallel in either patient. Thus, the
      suppressive effects of the analogue on the secretions of PST and CGA may be
      different. The results suggest the value of the PST and CGA assays used in this
      study.

PMID- 7630319
TI  - Griseofulvin: generation time and ATP changes in the ciliate Tetrahymena
      pyriformis.
AB  - Tetrahymena pyriformis GL populations (20,000 cells/ml and 50,000 cells/ml) were
      studied at various times after exposure to griseofulvin. Growth rates were
      significantly different between controls and treated samples 90 min after
      treatment. ATP levels decreased in treated samples after 45 min. No differences
      were observed between controls and populations treated with acetone used to
      dissolve griseofulvin.

PMID- 7630320
TI  - Is intestinal cytosolic glutathione S-transferase an alternative detoxification
      pathway in two-thirds hepatectomized rats?
AB  - The present study was designed to investigate the effect of partial (two-thirds)
      hepatectomy (PH) on hepatic and intestinal glutathione S-transferases (GSTs)
      activities. A significant decrease of cytosolic hepatic GSTs activity was
      observed after the PH. The lowest value of hepatic GSTs was obtained 48 h after
      the surgery. On the other hand, intestinal GSTs activities increased after PH,
      reaching the highest values 48 h after the hepatic lobes resection. The hepatic
      GSTs activities diminution was attributed, in part, to the high accumulation of
      bile acids in the liver tissue of hepatectomized rats, also demonstrated by a
      higher retention of [14C] taurocholate. The kinetic analysis performed with 1
      chloro-2,4-dinitrobenzene (CDNB) as substrate showed two sets of parameters,
      indicating the presence of isozymes of high and low affinities. Vmax1 and Vmax2
      were lower in PH rats suggesting a non competitive inhibition mechanism. The
      inhibitory effect of bile acids decreased during liver regeneration process of
      hepatectomized rats disappearing at 7 days after PH. Conversely, in non
      regenerating rats (GABA treated) the inhibitory mechanism was still observed at 7
      days after the surgery. The increase of intestinal GSTs activities (isozymes of
      high and low affinities) was attributed to the presence of polyamines, mainly
      putrescine, produced during the hepatic regeneration process. In this regard, it
      was showed that GABA treatment, which inhibits polyamine synthesis, completely
      abolished the increase on intestinal GSTs activities. Finally, the treatment with
      exogenous putrescine showed that in hepatectomized and sham-operated rats, the
      polyamine induced GSTs activities in both tissues. In PH rats, the putrescine
      dependent increase of hepatic GSTs was masked by the inhibitory effect of bile
      acids. In addition, a summation effect of endogenous and exogenous putrescine was
      probably the reason of the induction of intestinal GSTs after PH. The GSH/GSSG
      ratio did not change during the treatments, as well as the microsomal GST
      activity of both tissues. The work points out the hypothetical detoxification
      power of the intestine during the hepatocellular insufficiency which follows a
      two-thirds hepatectomy.

PMID- 7630321
TI  - Effect of gastrin-releasing peptide (GRP) and GRP antagonists on TSH secretion
      from rat isolated pituitaries.
AB  - It has previously been demonstrated that gastrin releasing peptide (GRP), a
      bombesin-like peptide, inhibited TSH release "in vivo". In this study, we have
      shown that GRP acts directly at the pituitary gland, inhibiting basal and TRH
      stimulated TSH release from incubated rat anterior pituitary glands. This effect
      was observed at the highest GRP concentration (10(-5) M), but not at the lower
      concentrations (10(-7) and 10(-9) M). Incubation of the glands with two
      antagonists of GRP (d-Phe8-GRP and Gly6-GRP) induced an increase of basal TSH
      secretion. We suggest a physiological role of locally produced bombesin-like
      peptides in the control of TSH release. Another antagonist (Ala6-GRP) did not
      change TSH secretion. This result suggests the existence of different subtypes of
      GRP receptors in the anterior pituitary gland.

PMID- 7630322
TI  - Group A streptococci: evaluation of in vitro resistance to two macrolides.
AB  - In recent years an increase in severe group A streptococcal infections has been
      observed. The possible relation between the failure of therapy and an increase of
      resistance to antibiotics, which are often used for streptococcal infections
      (clarithromycin and erythromycin), has been assessed in vitro. Streptococcus
      pyogenes strains tested for susceptibility were isolated in different years from
      pharyngotonsillar swabs of symptomatic children and typed; another nine strains
      came from the American Type Culture Collection. The evaluation of antimicrobial
      activity demonstrated that the percentage of resistance of these bacteria to the
      two macrolides was 4, 4.4 and 15.5%, respectively, for strains isolated in 1990,
      1991 and 1994. Clarithromycin showed a better antistreptococcal, above all
      bactericidal, activity. The presence of M protein in streptococci does not seem
      to modify the kinetic activity of the two drugs, while a slower bactericidal
      effect was observed against capsulated strains. The resurgence of severe group A
      Streptococcus infections may be due to an increase in the circulation of strains
      with a capsule expression, which is critical also for resistance to phagocytic
      killing.

PMID- 7630323
TI  - Quantitative effects of redox-cycling chemicals on the oxidant-sensitive enzyme
      dihydroxy-acid dehydratase.
AB  - The [4Fe-4S] cluster-containing enzyme dihydroxy-acid dehydratase (DHAD) is
      susceptible to inactivation by dioxygen and active oxygen species including
      superoxide with an inactivation rate constant of 10(6) m-1 sec-1. Based on this
      property, DHAD was used to quantify and investigate the biological oxidant stress
      activity of various redox-cycling chemicals. Exponentially growing cultures of
      Escherichia coli were used as a sensitive source of the DHAD enzyme. The effects
      on DHAD of compounds with and without established redox activity, under aerobic
      and anaerobic (control) conditions were measured. Paraquat, juglone,
      nitrofurantoin, the nitrofuran related compound NF-963 which is 6,7-dihydro-3-(5
      nitro-2-furyl-5H-imidazo-[2,1-b] thiazolium chloride), plumbagin, benzoquinone,
      duroquinone, hydralazine, and naphthalene inhibited DHAD activity and the
      concentrations required for 50% inhibition ranged from 3.5 microM for paraquat to
      950 microM for naphthalene. Eleven other agents tested (including 4,4-dipyridyl
      which is a non-redox-cycling compound similar to paraquat and an extract and two
      compounds of plant origin) did not inhibit DHAD. The DHAD technique described is
      a useful means of detecting and comparing the oxidant-stress toxicity and
      mechanism of action of chemicals by a biological means on a quantitative scale
      relatable to paraquat.

PMID- 7630324
TI  - Antimicrobial activity of essences from labiates.
AB  - Bacteria, filamentous fungi and yeasts were subjected to the action of Lavandula
      officinalis, Melissa officinalis and Rosmarinus officinalis essences in a steam
      phase, using a microatmospheric technique. Due to the methodology employed, L.
      officinalis essence was more active in filamentous fungi than the other essential
      oils studied. All three essences possessed a similar degree of activity against
      the micro-organisms tested, though a relatively higher activity was seen in the
      case of M. officinalis.

PMID- 7630325
TI  - Effects of selected synthetic compounds on growth of Mucor rouxii.
AB  - The in vitro activity of four synthetic compounds was tested on fungal cells from
      Mucor rouxii. The compounds included phenylenediamine, two phenolamines, and
      quinone. At the concentrations tested (10(-2)-10(-4)M) the compounds exhibited
      antifungal activity, with the exception of quinone. On the basis of their effects
      on spore germination, and development of hyphae, phenylenediamine was the more
      active. The mechanism of action of the compounds is still unknown, but hyphae
      show morphological alterations and disturb the distribution of calcofluor in the
      cell wall. This suggests variations in the genesis of the cell wall.

PMID- 7630326
TI  - Broth micro-dilution method for determining the susceptibility of Escherichia
      coli and Staphylococcus aureus to the essential oil of Melaleuca alternifolia
      (tea tree oil).
AB  - A broth micro-dilution method was used to examine the susceptibility of
      Escherichia coli (n = 110) and Staphylococcus aureus (n = 105) to the essential
      oil of Melaleuca alternifolia (tea tree oil). The detergent Tween 80 was used
      successfully to enhance the solubility of tea tree oil in the test medium. The
      MIC90 of tea tree oil for E. coli was 0.25% while for S. aureus it was 0.50%.

PMID- 7630328
TI  - Vinorelbine for treatment of advanced non-small-cell lung cancer.

PMID- 7630327
TI  - Protective effect of amphotericin B against lethal photodynamic treatment in
      yeast.
AB  - The effect of polyenic antibiotic amphotericin B on photodynamically induced cell
      damage was investigated using Kluyveromyces fragilis. The photosensitizers
      applied are known to act via cell membrane damage (rose bengal and toluidine
      blue) or via DNA modification causing genotoxic effects (8-methoxypsoralen).
      Methylene blue was shown to cause membrane damage comparable with the effect of
      rose bengal and toluidine blue. Under conditions of photodynamic damage a
      pronounced protective effect of the antibiotic was evident in increased cell
      survival with all of the photosensitizers tested. Mitochondrial activity
      indicated a tendency of the antibiotic to protect the cells. The protective role
      of amphotericin B is discussed in the light of possible implications for
      photodynamic therapy of microbial infections.

PMID- 7630329
TI  - Grapefruit juice interactions with drugs.

PMID- 7630330
TI  - Recognition, stabilization, and early management of infants with critical
      congenital heart disease presenting in the first days of life.
AB  - The incidence of infants born with congenital heart disease (CHD) is about 0.8%
      of all live births. Out of this at-risk population, approximately one-third will
      develop life-threatening symptoms of critical CHD within the first few days of
      life. These infants present the neonatal team with a variety of challenges, and
      require early identification along with proper stabilization and treatment to
      survive. The neonatal nurse plays a vital role in recognizing the first signs and
      symptoms of cardiac distress. This article discusses the most common life
      threatening congenital cardiac lesions, reviews their pathophysiology, and
      outlines the initial medical and nursing management. A through understanding of
      these concepts can help the nurse improve patient outcomes.

PMID- 7630331
TI  - Reliability of in-bed weighing procedures for critically ill infants.
AB  - The purpose of this study was to describe the intra- and interexaminer
      reliability of weight measurements obtained from critically ill infants on an in
      bed electronic scale. Weight measurements were obtained using the in-bed scale
      (Smart Model 35, Olympic Medical, Seattle, Washington) for 32 infants; 16 were in
      an incubator, and 16 were under a radiant warmer. Two nurses each obtained two
      weight measurements for each infant for three consecutive days, for a total of 96
      data collection sessions. The nurses were blinded to their own and to the other
      nurse's weight measurements. The average mean absolute difference for individual
      nurses' weight measurements (interexaminer reliability) was 12.58 gm for weights
      obtained in the incubator and 19.19 gm for weights obtained under the radiant
      warmer. The average mean absolute difference for pairs of nurses' weight
      measurements (interexaminer reliability) was 14.29 gm for weights obtained in the
      incubator and 24.42 gm for weights obtained under the radiant warmer. The average
      mean absolute differences for weights obtained in the two bed types differed
      significantly for both intra- (Z = -2.46, p = .0141) and interexaminer (Z = 
      3.11, p = .0019) reliability. The number of pieces of equipment that had to be
      held during the weight measurement was weakly correlated with both the intra- (rs
      = .1878, p = .0091) and interexaminer (rs = .1600, p = .0266) mean absolute
      differences. These findings suggest that weight measurements of critically ill
      infants obtained using the Smart Model 35 in-bed electronic scale are
      sufficiently reliable for calculation of medication, parenteral fluid, blood
      replacement, and nutritional requirements.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7630332
TI  - Accuracy and precision of neonatal electronic incubator scales.
AB  - Measurement of weight in the neonatal intensive care unit demands accuracy and
      precision. To date, however, no studies exist that independently document the
      accuracy of infant incubator bed scales. The purpose of this study is to evaluate
      the Airshields-Vickers Warm Weigh internally mounted incubator bed scale with
      foam and water mattresses using 500 gm and 1,500 gm standard weights to ascertain
      the precision of electronic bed scales and to evaluate the differences between
      nurse weighers. Two experienced neonatal nurses evaluated new incubator bed
      scales. Each nurse independently collected data and kept the results masked.
      Eight measurements were obtained from each incubator. Results indicated error
      beyond +/- 2 gm at 500 gm with the foam mattress and in both weight groups with
      the water mattress using the Technical Error Measurement (TEM) method. This
      indicates that the bed scales did not perform within the manufacturer's rated
      accuracy of +/- 2 gm at the smallest weights found in the clinical area. Weight
      errors were not judged to be clinically significant by a group of NNP experts.

PMID- 7630333
TI  - Renal physiology. Part II: Fluid and electrolyte regulation.
AB  - The comprehension of fluid and electrolyte and acid-base homeostasis is essential
      for the nurse caring for critically-ill neonates. This article discusses the
      means by which the kidney regulates fluid, sodium, and potassium, and its role in
      acid-base regulation. Under normal circumstances, the neonatal kidney is able to
      maintain homeostasis in these areas. However, the more premature an infant, the
      less able they are to maintain normal electrolyte, bicarbonate, or fluid balance.
      The understanding of renal filtration, absorption, and excretion requires
      knowledge of renal anatomy and the structure and function of the nephron unit.
      Regulation of glomerular filtration and renal blood flow plays an important part
      in determining the kidney's ability to maintain homeostasis (see Part I). Perhaps
      the greatest factor in determining renal function is the degree of maturity.
      Nephrogenesis is not complete until the 34th week of gestation. This, along with
      other factors, has a profound effect on glomerular filtration, renal filtration
      and absorption, and the nephron's sensitivity to hormonal control. The structural
      and functional differences in the neonatal kidney must be considered when
      evaluating renal function and devising a plan of care.

PMID- 7630334
TI  - NANN Board of Directors approves position statements.

PMID- 7630335
TI  - Research utilization: nonpharmacological management of pain in neonates.

PMID- 7630336
TI  - Tromethamine (THAM).

PMID- 7630337
TI  - Going to the show.

PMID- 7630338
TI  - Injuries associated with self-unloading forage wagons--New York, 1991-1994.
AB  - In New York, an estimated 3600 injuries occur each year to farmers operating farm
      machines (1). In October 1993, the Occupational Health Nurses in Agricultural
      Communities (OHNAC) program in the New York State Department of Health received a
      report of a man who sustained severe injuries when he became entangled in the
      power take-off (PTO) driveline to a self-unloading forage wagon. Subsequent
      investigation by OHNAC identified four additional similar incidents in New York
      that occurred during September 1991-October 1994, including one fatality and one
      injury to a 9-year-old girl working on a family farm. This report summarizes the
      results of the investigation of these forage-wagon-related injuries and presents
      recommendations to reduce the risk for such injuries.

PMID- 7630339
TI  - Update: HIV-2 infection among blood and plasma donors--United States, June 1992
      June 1995.
AB  - Human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) both cause
      acquired immunodeficiency syndrome (AIDS). Following the licensure of combination
      HIV-1/HIV-2 screening enzyme immunoassays (EIA), the Food and Drug Administration
      (FDA) recommended that beginning in June 1992 all donated whole blood, blood
      components, and source plasma be screened for antibody to HIV-2 because not all
      persons infected with HIV-2 can be detected by HIV-1 testing (1,2). This report
      describes the first two cases of HIV-2 infection detected among potential blood
      donors since the implementation of recommended HIV-2 screening and summarizes
      national data about persons known to be infected with HIV-2 during December 1987
      June 1995.

PMID- 7630340
TI  - AAEM minimonograph #16: instrumentation and measurement in electrodiagnostic
      medicine--Part I.
AB  - Technical and instrumentation factors play an important role in obtaining
      reliable information during electrodiagnostic studies. With contemporary
      electrodiagnostic equipment, neurophysiologic potentials are detected using a
      variety of electrodes and undergo differential amplification, filtering,
      conversion to digital form, and finally, analysis and display. Understanding the
      signal processing principles, limitations, and sources of errors that can occur
      during this multistep process can improve the technical quality of studies,
      minimize preventable errors, and improve clinical interpretation. Part I of this
      minimonograph reviews the basic principles of action potential generation and
      overviews electrodiagnostic instrumentation. The concept of waveform frequency
      content is related to the role of filters in suppressing noise while preserving
      waveform latency, amplitude, and morphology. The electrical characteristics of
      various surface and needle electrodes influence instrument design and the nature
      of the potentials recorded. This is especially important in understanding the
      differences in motor unit characteristics obtained from monopolar and concentric
      needle electrodes.

PMID- 7630341
TI  - AAEM minimonograph #16: instrumentation and measurement in electrodiagnostic
      medicine--Part II.
AB  - A review of instrumentation and measurement in electrodiagnostic medicine is
      continued in this Part II which focuses on digital instrumentation principles,
      gain and sweep effects, noise, nerve stimulation, and conduction measurement
      limitations. With the adoption of microprocessor-based equipment, the
      neurophysiologic signal must undergo analog-to-digital conversion (ADC) before
      analysis and display on a video monitor. ADC resolution and sampling rates affect
      accuracy and measurement precision. Following waveform display, the visual
      assessment of latency and duration may be influenced by sweep and gain settings,
      often overlooked sources of error. Undesired signal or noise typically originates
      from power-line interference, electronic amplifier noise, background muscle
      activity, or nerve stimulation artifact. Noise often interferes with clinical
      studies but techniques exist to reduce noise to acceptable levels in virtually
      all situations. An awareness and understanding of these technical issues will
      lead to an appreciation of the limitations of electrodiagnostic testing and
      improve interpretation and clinical decision-making.

PMID- 7630342
TI  - AAEM minimonograph #45: the early development of electromyography.
AB  - The use of electricity for therapeutic purposes began in the first century and
      became more refined as the properties of electricity became more understood. The
      works of Franklin, Galvani, Volta, and others contributed to this body of
      knowledge. Development of the string galvanometer, the advent of the vacuum tube,
      the introduction of concentric needle electrodes, and the development of the
      cathode-ray oscilloscope occurred during the first half of the 20th century. The
      science of electromyography and electrodiagnosis grew in its sophistication,
      leading to the formation of the American Association of Electromyography and
      Electrodiagnosis (now the American Association of Electrodiagnostic Medicine)
      with James Golseth, MD, as its first president in 1953.

PMID- 7630343
TI  - Pretreatment of myoblast cultures with basic fibroblast growth factor increases
      the efficacy of their transplantation in mdx mice.
AB  - The effect of pretreatment of cultures with basic fibroblast growth factor (bFGF)
      on myoblast allotransplantation to C57BL/10ScSn mdx/mdx mouse (mdx mouse) muscles
      not previously damaged and not irradiated was studied. Transgenic CD1 mice which
      have a beta-galactosidase gene under the control of the promoter of the quail
      fast skeletal muscle troponin I gene, were used as donors. The myoblasts were
      grown with 100 ng/mL bFGF during the last 2 days before injecting them in the
      left tibialis anterior (TA) muscles of mdx mice. Myoblasts from the same primary
      cultures were also grown without bFGF and injected in the right TA muscles as
      control. The recipient mice were immunosuppressed with FK 506. Twenty-eight days
      after myoblast transplantation, the percentage of beta-galactosidase-positive
      fibers was significantly higher (more than fourfold) following culture with bFGF
      than without bFGF. Almost all beta-galactosidase-positive fibers were also
      dystrophin positive. Direct intramuscular injections of bFGF or of Hank's
      balanced salt solution (HBSS) at the time of myoblast transplantation and at
      several intervals afterwards were also investigated. The percentage of beta
      galactosidase-positive fibers did not differ significantly following
      intramuscular injection of bFGF from controls injected with HBSS. In vitro, this
      high concentration of bFGF significantly reduced the formation of myotubes, and
      the percentage of mononuclear cells which were myoblasts was significantly
      increased by 34%. These observations alone do not account for the fourfold
      increase in transplantation success. The presence of bFGF in the culture did not
      significantly increase the cell survival 3 days after their
      transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7630344
TI  - Childhood-onset oculopharyngodistal myopathy with chronic intestinal pseudo
      obstruction.
AB  - Oculopharyngodistal myopathy is characterized by the adult onset of ptosis,
      external ophthalmoplegia, dysphagia, and distal weakness. Although dysphagia is
      common, other gastrointestinal involvement has not been described. We report a
      case with childhood onset who developed chronic intestinal pseudo-obstruction.
      Other myopathies associated with ophthalmoplegia and intestinal pseudo
      obstruction such as mitochondrial cytopathies were excluded. Whether
      oculopharyngodistal myopathy is a variant of oculopharyngeal muscular dystrophy
      or a distinct neuromuscular disorder is unknown and requires further study.

PMID- 7630345
TI  - Involvement of the external anal sphincter in amyotrophic lateral sclerosis.
AB  - In amyotrophic lateral sclerosis the striated pelvic floor sphincter muscles are
      functionally uninvolved, and pathological studies have confirmed the relative
      resistance of the Onuf nucleus motor neurons. We have evaluated the external anal
      sphincter (EAS) muscle in 16 patients with ALS using single fiber EMG, and
      compared the results with the findings in the semimembranosus-semitendinosus (SM
      ST) muscles that have innervation from the L-5, S-1, and S-2 segments. The
      results were compared with a group of controls matched for age and sex. None of
      the patients or controls had symptomatic sphincter involvement and none of the 4
      women studied were parous. Eight patients with ALS showed an increased fiber
      density in the EAS; 6 had an abnormal neuromuscular jitter. In 1 there was
      fibrillation in the EAS. In the SM-ST muscle 11 patients showed an increased
      fiber density, and 7 had an abnormal neuromuscular jitter. In 3 patients with ALS
      in whom there were abnormal findings in the EAS the bulbocavernosus reflex and
      pudendal nerve evoked potentials were normal. Neurogenic change was more marked
      in the SM-ST than in the EAS muscle. These findings show that the EAS is not
      normal in ALS. However, the relative resistance of the EAS to ALS is sufficient
      to prevent incontinence, even in the longer-surviving older patients.

PMID- 7630346
TI  - Detection of HTLV-I provirus by in situ polymerase chain reaction in mononuclear
      inflammatory cells in skeletal muscle of viral carriers with polymyositis.
AB  - We tested for HTLV-I proviral DNA in skeletal muscle from patients with
      polymyositis infected with HTLV-I using the in situ polymerase chain reaction. We
      found the HTLV-I provirus in some of the CD4-positive cells in HTLV-I-positive
      polymyositis cases but not in HTLV-I-negative polymyositis ones. We could not
      detect HTLV-I within the muscle fibers. We suggest that HTLV-I-associated
      polymyositis is not due to direct, persistent infection of the muscle fiber by
      the virus, but to a T-cell-mediated immunological process triggered by the HTLV-I
      infected cells.

PMID- 7630347
TI  - Recovery of sensation and somatosensory evoked potentials following toe-to-digit
      transplantation in man.
AB  - Recovery of digital nerve function in 21 patients with toe-to-digit
      transplantation was evaluated by clinical sensory tests and somatosensory evoked
      potentials (SEPs) to median and digital nerve stimulation. The mean interval
      between injury and surgery was 7 months, and that between surgery and study was
      31 months. The transplanted toes achieved a satisfactory but incomplete recovery
      in temperature (warm and cold), pinprick, touch, vibration, and two-point
      discrimination in that order. The overall sensory status of the transplanted toes
      appeared to be closer to normal toes than to normal fingers. In SEPs from the
      transplanted side, median N9, N13, and N20 components had normal latency but
      reduced amplitude, whereas digital N9 component was usually absent, but N13 and
      N20 components had prolonged latency and reduced amplitude. Transplantation
      performed within 1 month after injury prevented amplitude reduction in median
      SEPs and latency prolongation in digital SEPs. The SEP data suggest that timing
      of surgery was critical in preventing retrograde effect on the median nerve, and
      that recovery of digital nerve function was incomplete correlating with clinical
      sensory findings.

PMID- 7630349
TI  - Characterization of the glycolysis in lactate dehydrogenase-A deficiency.
AB  - Recurrent rhabdomyolysis due to decreased glycolysis occurred during strenuous
      exercise by patients with lactate dehydrogenase-A subunit (LDH-A; muscle)
      deficiency. We report the glycolytic features of 4 patients from 2 families in
      whom the severity of the disease differed. There was no difference in the gene
      abnormality. The enzyme activity of LDH in the muscle was less than 5% that of
      the control value. Glycolysis in the muscle showed that the respective sums of
      the pyruvate and lactate levels in the patients with mild and severe symptoms
      were reduced to approximately 65% and 35% that of the control value. Comparable
      amounts of glycerol 3-phosphate were produced. Glycerol 3-phosphate dehydrogenase
      activity in the muscles of patients with mild symptoms was three times the
      control value. These findings suggest that the disease severity in our patients
      may be related to the degree of NADH reoxidation by glycerol 3-phosphate
      dehydrogenase substituting for LDH.

PMID- 7630348
TI  - Peroneal nerve repetitive nerve stimulation test: its value in diagnosis of
      myasthenia gravis and Lambert-Eaton myasthenic syndrome.
AB  - We have developed a repetitive nerve stimulation (RNS) technique for the peroneal
      nerve. Normal limits for the decremental responses for the anterior tibialis and
      extensor digitorum brevis muscles are 6-21% at the low rate of stimulation and 44
      70% at the high rate of stimulation. These values exceed the normal limits for
      other commonly tested muscles. This may be due to the lower safety factor for
      neuromuscular transmission for the anterior tibialis and extensor digitorum
      brevis muscles. We present 4 cases in which the peroneal nerve RNS test was
      crucial for the diagnosis of the limb-girdle form of MG or LEMS. Thus, we
      conclude that, in a small number of patients with neuromuscular transmission
      disorders, the peroneal nerve RNS test is needed for confirmation of disease.

PMID- 7630350
TI  - The utility of various sensory nerve conduction responses in assessing brachial
      plexopathies.
AB  - To determine which sensory nerve conduction studies (S-NCS) are helpful in
      detecting supraclavicular axon loss brachial plexopathies, we selected 53 cases
      (of 417 reviewed) in whom complicating factors were absent and which, by needle
      electrode examination findings, involved only a single "truncal" element (upper,
      middle, or lower) of the brachial plexus. Extensive S-NCS included: median,
      recording thumb (Med-D1), index (Med-D2), and middle fingers (Med-D3); ulnar,
      recording fifth finger (Uln-D5); dorsal ulnar cutaneous, recording dorsum of the
      hand (DUC); radial, recording base of thumb; and both medial and lateral
      antebrachial cutaneous (MABC, LABC), recording forearm. Except for the median
      sensory fibers, the "cord" elements traversed by the sensory fibers assessed
      during the S-NCS listed above are anatomically defined (i.e., the sensory fibers
      enter the brachial plexus at only one cord). In regard to the median sensory
      fibers, however, there are two possible pathways through the infraclavicular
      plexus: (1) the lateral cord and/or (2) the medial cord. Because the lower trunk
      is only accessible via the medial cord, any sensory fibers found to be traversing
      the lower trunk had to first traverse the medial cord. Similarly, those
      traversing the upper and middle trunks must first be a component of the lateral
      cord. The frequency that the various S-NCS responses were abnormal (unelicitable,
      below laboratory normal value, or < or = 50% of the contralateral response) for a
      given brachial plexus element lesion was as follows: (1) upper trunk (UT): 25 of
      26 Med-D1, 25 of 26 LABC, 15 of 26 radial, 5 of 26 Med-D2, 2 of 26 Med-D3; (2)
      middle trunk (MT): 1 of 1 Med-D3; (3) lower trunk (LT): 25 of 26 Uln-D5, 22 of 23
      DUC, 11 of 17 MABC, 3 of 23 Med-D3. With lower trunk brachial plexopathies, both
      "routine" (Uln-D5) and "uncommon" (DUC; MABC) S-NCS are abnormal. With upper
      trunk brachial plexopathies, in contrast, only the "uncommon" S-NCS (Med-D1;
      LABC) are consistently affected. The "routine" median S-NCS recording digit 2
      (Med-D2) is far less reliable than the median S-NCS recording digit 1 (Med-D1) in
      detecting upper trunk axon loss brachial plexopathies. Additionally, the various
      pathways traversed by the fibers contributing to the individual S-NCS responses
      can be predicted, an important point when the full extent of a brachial plexus
      lesion is sought.

PMID- 7630351
TI  - High-frequency fatigue in rat skeletal muscle: role of extracellular ion
      concentrations.
AB  - High-frequency fatigue (HFF), the decline of force during continuous tetanic
      stimulation (lasting 4-40 s), was studied in isolated bundles of rat skeletal
      muscle fibers. HFF was slower in slow-twitch soleus fibers than in fast-twitch
      red or white sternomastoid fibers; denervation accelerated fatigue in soleus.
      Maximal 200-mmol/L potassium contractures of normal amplitude were induced in
      fatigued fibers, suggesting that crossbridge cycling and the voltage activation
      of excitation-contraction coupling could still occur maximally, but that
      activation by action potentials was impaired. An increase in [Na+]o slowed HFF,
      while a small increase in [K+]o or reduction in [Cl(-)]o accelerated HFF.
      Increasing the tetanic stimulation frequency exacerbated fatigue. Recovery from
      HFF proceeded rapidly since force increased markedly within a few seconds when
      stimulation ceased. These results support the hypothesis that a redistribution of
      Na+, K+, and Cl- across the transverse tubular membranes during repeated action
      potential activity induces fatigue by reducing the amplitude and conduction of
      action potentials.

PMID- 7630352
TI  - Foot drop as a harbinger of aortic occlusion.
AB  - A man presented with foot drop and 2 months later an infrarenal occlusion of his
      abdominal aorta was discovered. Initial evaluation found no structural etiology
      for his nerve injury. His neurologic deficits progressed until gangrenous changes
      developed in his feet leading to the discovery of aortic occlusion. This case
      demonstrates that peripheral nerve injury in the legs may signal underlying large
      vessel occlusive disease. We discuss the localization and potential mechanisms of
      ischemic nerve injury.

PMID- 7630353
TI  - Motor evoked potentials to magnetic stimulation in chronic and acute inflammatory
      demyelinating polyneuropathy.

PMID- 7630354
TI  - CMAP variation over a length of nerve in diabetic neuropathy.

PMID- 7630355
TI  - Altered distribution of beta-dystroglycan in sarcolemma of human dystrophic
      muscles: an immunohistochemical study.

PMID- 7630356
TI  - Transient myasthenia gravis during HIV infection.

PMID- 7630357
TI  - Abnormal sympathetic skin response in patients with palmar hyperhidrosis.

PMID- 7630358
TI  - The medial calcaneal nerve: anatomy and nerve conduction technique.

PMID- 7630359
TI  - A confusing case of Miyoshi distal myopathy.

PMID- 7630360
TI  - Sensory thresholds in older adults: reproducibility and reference values.

PMID- 7630361
TI  - Traumatic lesion of the common peroneal nerve with complete foot drop and
      preserved dorsiflexion of the toes--an innervation anomaly.

PMID- 7630362
TI  - Stimulus-induced repetitive discharges of long latency: axonal loop reflexes.

PMID- 7630363
TI  - HTLV-1 associated pandysautonomia with adrenal dysfunction.

PMID- 7630364
TI  - Switching device for botulinum toxin injection guidance.

PMID- 7630365
TI  - [Post-antibiotic effect and post-exposure polyene antagonism of azole
      antimycotics in Candida albicans: dependency on lipophilia].
AB  - With the lipophilic azoles itraconazole (ICZ), ketoconazole (KCZ), and miconazole
      (MCZ) two effects, occurring in parallel, on Candida albicans were observed:
      Firstly, these azoles caused a growth inhibition which persisted for at least 24
      hours (post-antibiotic effect, found regularly with KCZ and MCZ, with ICZ only
      occasionally). Furthermore, the fungicidal activity of amphotericin B (AMB, 1
      mg/1) after exposure to the azoles was reduced. In contrast, to this, fluconazole
      (FCZ) produced neither of these effects. Additional experiments indicate that
      both actions of the three lipophilic azoles may be related to their noncovalent
      binding to lipophilic cytoplasmatic components of the yeast cells. In the case of
      fluconazol such bonds seem to be much weaker. Presumably, the amount of the
      relatively hydrophilic fluconazole, which will be bound to the cell, is too low
      as to produce long lasting post-exposure effects like those caused by the
      lipophilic azoles.

PMID- 7630366
TI  - [Growth of Candida albicans in normal and altered fecal flora in the continuous
      flow culture model].
AB  - We used the model of fecal microflora under continuous flow culture (cfc)
      conditions to study the growth of Candida albicans in mixed cultures. The
      development of Candida is usually limited by the high germ counts of aerobic and
      anaerobic bacteria. Neither by the continuous inflow of C. albicans-cfc
      monocultures nor by intermittent input of highly concentrated suspensions of C.
      albicans into the system a growth in fecal flora could be obtained. If the system
      was run under aerobic conditions a development of C. albicans with few hyphal
      growth could be observed. After some days however, the fecal flora again
      suppressed a further development of the yeasts. Only a marked destruction of the
      aerobic and anaerobic microflora by antibiotics resulted in a growth or
      overgrowth of Candida albicans.

PMID- 7630367
TI  - [Laboratory diagnostic peculiarities of mycoses in immunosuppressed patients].
AB  - Domestic invasive mycoses are typically present as secondary diseases in patients
      definitely immunocompromised. This truth should not obscure the fact that a
      transient overload of the immune system, e.g. in the polytrauma patients, may
      likewise favour the development of mycoses. The two groups of patients show a
      comparable course of infection and, to some extent, diagnostic signs:
      surveillance cultures and monitoring of antibodies are more helpful with trauma
      patients and less reliable in the typically immunocompromised patients. In the
      latter, however, antigen tests may yield more reliable results than in the trauma
      patients. The different functional capacities of the immune system in the two
      groups of patients may also affect the appearance of fungal elements,
      particularly of aspergilli, in secretions and biopsies.

PMID- 7630368
TI  - [Changes in the fungal spectrum of dermatomycoses].
AB  - The spectrum of aetiologic agents isolated from 3607 patients suspicious for
      dermatomycosis being in the care of the Berlin Charite Clinics was analysed.
      Identification of dermatophytes and moulds were performed conventionally. For the
      identification of yeasts biochemical and genetic methods were used. Among the
      dermatophytes in comparison of present with previous incidence rates changes can
      be observed. Opportunistic yeasts are recognized in increasing importance. Five
      fungal species are forming a stable base of aetiologic agents of dermatomycoses,
      i.e. Trichophyton rubrum, T. mentagrophytes, Candida albicans, C. parapsilosis
      and Trichosporon cutaneum, completed by increasing incidence of Microsporum
      canis, T. mentagrophytes var. granulosum and T. tonsurans.

PMID- 7630369
TI  - [HIV-associated mycoses].
AB  - Candidosis, cryptococcosis, and histoplasmosis often occur as HIV-associated
      mycoses. However, aspergillosis can be observed quite recently. The morphology of
      the pathogen of HIV-associated mycoses in vivo and in vitro is demonstrated and
      discussed.

PMID- 7630370
TI  - [Prophylaxis and therapy of fungal infections in oncology].
AB  - The observation of a considerable incidence of fungal infections in oncology
      patients has promoted a large number of studies both on prophylaxis and treatment
      in this patient group. Trials using triazoles, especially fluconazole, have shown
      effect in preventing fungal infections. In neutropenic patients, their role in
      therapy still remains less clear. Amphotericin B is the drug of choice for most
      life-threatening infections. With this drug, efforts concentrate upon the
      amelioration of side effects by sodium loading, administration in lipid emulsions
      or liposomes. The use of AMB as low-dose systemic prophylaxis or by inhalation
      needs further study.

PMID- 7630371
TI  - [Mycotic complications in patients with chronic liver diseases and pancreatitis].
AB  - We studied 15 patients with mostly alcoholic liver diseases and 25 patients with
      acute or chronic pancreatitis with regard to occurrence of yeasts in different
      microbiological samples and corresponding serological findings. In about a half
      of the patients with liver diseases yeast counts and serological titres were
      already raised in the first mycological investigation. Patients with
      pancreatitis, however, showed only little or negative cultural and serological
      results. This changed during the course of disease, where they developed
      significantly higher yeast counts and serotitres. Finally two case reports are
      presented: two patients with infected pancreatic pseudocysts (including a case of
      aspergillosis). CONCLUSIONS: in patients with decompensated chronic liver
      diseases an early search for mycological complications is recommended. In
      pancreatic diseases these complications are rather seen later in the course of
      the disease, especially under intensive care conditions. Therefore, we encourage
      surveillance cultures and control of serotitres in these patients.

PMID- 7630372
TI  - [Comparison of seven methods of in vitro susceptibility testing of clinical yeast
      isolates against fluconazole].
AB  - Four commercially available in vitro test systems (Candifast, E-test, Mycototal,
      Spiral-Gradient Endpoint Method), agardiffusion with 25 micrograms fluconazole
      paper test discs and 15 micrograms test tablets, and agardilution were compared
      to the microbroth dilution method by fluconazole susceptibility testing of 145
      clinical isolates. In addition, the culture media provided or recommended by the
      manufacturers of the test systems were compared to the high resolution (HR)
      antifungal test medium. With all currently available culture media growth
      problems (inhibition or delayed growth of the clinical isolates) occurred with
      solid or semi-solid media. With minor improvements, HR medium demonstrated the
      most reproducible and comparable results (supplementation with asparagine and
      deletion of sodium hydrogen carbonate). Best correlation to microdilution was
      obtained by the agardilution method > (95% concordance) followed by the spiral
      gradient endpoint method (85%), Candifast (83%), Mycototal (81%) and the E-test
      (78%). Regression analysis demonstrated good correlation between agardiffusion
      and micro-/agardilution(r > 0.9).

PMID- 7630373
TI  - [Mucocutaneous candidiasis in patients with skin diseases].
AB  - We investigated skin diseases associated with mucocutaneous Candida infection by
      analyzing the clinical records of 44695 in-patients of the department of
      dermatology of Kiel. For more than eighty skin diseases the relative risk (RR)
      was calculated by age-and sex-adjusting methods. 1996 patients demonstrated a
      mucocutaneous candidosis, 14.8% of them being hospitalized because of extensive
      Candida infection. In patients with dermatomyositis, bullous pemphigus, tinea
      inguinalis, and condylomata acuminata a Candida infection was observed more than
      threefold than expected. Furthermore, patients with urticaria, folliculitis, and
      bullous pemphigoid demonstrated candidosis more than twice as often as control
      patients. In addition, patients with erysipelas, acne, psoriasis, and atopic
      dermatitis showed a candidosis significantly more often (RR between 1.3 and 1.6).
      Some internistic maladies were investigated, too. In patients presenting with
      diabetes mellitus, heart-insufficiency, hypertension, chronic tonsillitis, and
      urinary tract infection a mucocutaneous Candida infection was significantly
      increased.

PMID- 7630374
TI  - Kinetoplastid membrane protein-11 (KMP-11) is differentially expressed during the
      life cycle of African trypanosomes and is found in a wide variety of
      kinetoplastid parasites.
AB  - An abundant 11-kDa membrane protein was purified from African trypanosomes by
      organic solvent extraction and octyl-Sepharose chromatography. This protein cross
      reacts with monoclonal antibodies originally generated against the
      lipophosphoglycan-associated protein of Leishmania donovani. Immunoblot analysis
      showed that the 11-kDa molecule was present in a variety of species of
      kinetoplastids. It was found in several species and subspecies of African
      trypanosomes and was present in low amounts in bloodstream forms and in larger
      amounts in procyclic, epimastigote and metacyclic life cycle stages. Expression
      of the 11-kDa molecule rapidly increased during transformation from bloodstream
      forms to procyclic forms, paralleling expression of the major surface
      glycoprotein of Trypanosoma congolense, the glutamic acid/alanine-rich protein,
      an analogue of T. brucei procyclin. The molecule was present in procyclic
      trypanosome membranes at approximately 2 x 10(5)-1 x 10(6) molecules per cell,
      suggesting it may have an important role in parasite membrane organization and
      function. Amino-acid analysis of the trypanosome 11-kDa protein showed it had a
      different composition than that of its leishmania counterpart. Its wide
      distribution in kinetoplastids and its membrane disposition suggest a name for
      this class of molecules: kinetoplastid membrane protein-11 (KMP-11).

PMID- 7630375
TI  - A mutation-specific PCR system to detect sequence variation in the
      dihydropteroate synthetase gene of Plasmodium falciparum.
AB  - Sulphur-based antimalarial drugs targeted at dihydropteroate synthetase (DHPS)
      are frequently used in synergistic combination with inhibitors of dihydrofolate
      reductase (DHFR) to combat chloroquine-resistant malaria. We have previously
      shown that lines of Plasmodium falciparum resistant to the most commonly used
      sulpha drug, sulphadoxine, carry point mutations in the DHPS coding region,
      relative to the sequence of sensitive strains (Brooks et al., Eur. J. Biochem.
      224 (1994) 397-405). We have now developed PCR diagnostic assays based on allele
      specific amplification that are able to detect such mutations. The four tests
      described can reliably discriminate all of the mutations observed to alter codons
      436, 581 and 613, yielding allele-specific amplification products of different
      sizes in each case. Moreover, by careful adjustment of primer length and the
      degree of mismatch to target and non-target alleles, we were able to standardise
      all four tests to a single set of PCR conditions, allowing all possible mutations
      to be monitored simultaneously on one thermocycler. These assays should prove
      invaluable in further assessing the contribution of specific base changes in the
      DHPS gene of the parasite to the sulphadoxine resistance phenotype and to the
      clinical failure of the sulphadoxine/pyrimethamine combination Fansidar.

PMID- 7630377
TI  - A new polymorphic marker for PCR typing of Plasmodium vivax parasites.

PMID- 7630376
TI  - Nicotinic acetylcholine receptors on the surface of the blood fluke Schistosoma.
AB  - Blood dwelling stages of schistosomes have acetylcholinesterase (AChE) on their
      teguments. As an initial step towards understanding the function of tegumental
      AChE, we have used specific ligand-binding assays to identify nicotinic
      acetylcholine receptors (nAChR) on the schistosome surface. AChR could not be
      detected on migratory stages using fluoroscein isothiocyanate-alpha-bungarotoxin
      binding but the amount of specific labelling increased on sexual pairing and as
      the parasites matured into egg-producing adults. Both AChE and nAChR were
      concentrated on the dorsal surface of the adult male. These results indicate a
      role for AChE and AChR associated with the transporting function of this
      membrane.

PMID- 7630378
TI  - Phylogenetic analysis of Gyrodactylus salaris Malmberg, 1957 based on the small
      subunit (18S) ribosomal RNA gene.

PMID- 7630379
TI  - Molecular cloning and characterization of a Cryptosporidium parvum elongation
      factor-2 gene.

PMID- 7630380
TI  - Characterization and detection of plant trypanosomatids by sequence analysis of
      the small subunit ribosomal RNA gene.
AB  - The complete sequences of the genomic small subunit ribosomal RNA gene from two
      Phytomonas isolates: one associated with palm pathologies (P. cocos FGuiana) and
      one found in lactiferous plants with no apparent pathology (P. Euphorbe Senegal),
      were analyzed. Partial sequences from a number of other Phytomonas isolates were
      also determined. The sequences obtained were used to determine the phylogenetic
      relationships between Phytomonas and other trypanosomatids as well as within the
      genus Phytomonas. The analysis showed that the intraphloemic isolates associated
      with pathologies in palm trees formed a homogeneous group that diverged from the
      more heterogeneous group of non-pathogenic isolates found in latex plant.
      Sequence comparisons of the full and partial SSU rRNA gene, identified sequences
      which are specific to the genus Phytomonas and an EcoRI restriction nuclease site
      which specifically identifies the Phytomonas isolates associated with diseases in
      palm trees.

PMID- 7630381
TI  - Essential components of the mini-exon gene promoter in the trypanosomatid
      Leptomonas seymouri.
AB  - In members of the Trypanosomatidae family of parasitic protozoa, the mini-exon
      (MX) genes encode the mini-exon donor RNA (medRNA) that contributes a small, 39
      nt exon to all pre-mRNAs during mRNA maturation. Previously we have shown that a
      single copy of a MX gene can be expressed continuously from a stable episome
      transfected into the monogenetic trypanosomatid Leptomonas seymouri. We now
      identify components of the MX gene promoter. A series of 10-bp block substitution
      mutations in a tagged MX gene were transfected into Leptomonas on an episomal
      vector. Expression of tagged and endogenous medRNA was assessed in stably
      transformed clonal cell populations. Results show that less than half of the 757
      bp MX gene is necessary for medRNA transcription and that the key components of
      the MX gene promoter lie within the proximal 70-bp sequence upstream from the
      transcription initiation site. Transcription requires several sequence-specific
      blocks within this 70-bp region. Leptomonas cell extracts contain protein(s) that
      appear to interact with a subset of these sequences in gel mobility shift assays.
      All trypanosomatid MX genes contain an AT-rich region at the +10 to +20 position
      within the transcribed region of the MX gene. Mutagenesis of this region within
      an episomal copy of the MX gene did not block tagged medRNA synthesis but did
      cause a 10-fold increase in the steady-state amount of endogenous medRNA.

PMID- 7630382
TI  - The gp15/400 polyprotein antigen of Brugia malayi binds fatty acids and
      retinoids.
AB  - Gp15/400 is a surface-proximal antigen of the filarial nematode Brugia malayi,
      produced as a large polyprotein precursor comprising an array of polypeptide
      units of approx. 14.5 kDa. Here we describe a biochemical function for gp15/400.
      A single 14.5-kDa unit of gp15/400 has been expressed in Escherichia coli, and
      found to dimerise spontaneously. This protein (designated P-RUNG) has high
      affinity fatty acid and retinoid binding activity, suggesting that the parent
      polypeptide itself has these properties. Fluorescent fatty acid probes show
      significant enhancement of fluorescence intensity and shifts in emission
      wavelength in the presence of P-RUNG, which can be reversed by competing non
      fluorescent fatty acids (oleic, palmitic, steric, arachidonic), retinoids
      (retinol and retinoic acid) and oleoyl Coenzyme A, but not by tryptophan,
      cholesterol, caproic acid, squalene, tocopherol, tocopherol acetate, succinyl
      CoA, 2-methylbutyric acid and 2-methylvaleric acid. Changes in intrinsic
      fluorescence of retinol or retinoic acid confirmed the retinoid binding function.
      The results of fluorescence titration experiments are consistent with
      stoichiometric binding to a single protein site per monomer unit with affinities
      (Kd) in the range 2 x 10(-6) M (for the fluorescent probe 11-((5
      dansyl)amino)undecanoic acid) and 2 x 10(-7) M (for oleic acid). The extreme blue
      shift of the fluorescent fatty acid-protein complex suggests an unusually low
      polarity for the protein binding site. The intrinsic fluorescence of the single
      tryptophan residue of P-RUNG indicates that it also is deeply buried in a non
      polar environment, but is probably not involved in ligand binding. Gp15/400,
      therefore, represents a new class of lipid binding protein which is possibly
      restricted to nematodes.

PMID- 7630383
TI  - Isolation and characterization of the gene encoding the surface membrane 3'
      nucleotidase/nuclease of Leishmania donovani.
AB  - Leishmania donovani and related trypanosomatid protozoa possess an externally
      oriented surface membrane enzyme capable of hydrolyzing both 3'-nucleotides and
      nucleic acids. By virtue of these activities, this 3'-nucleotidase/nuclease (3'
      NT/Nu), previously shown to be analogous to fungal and plant class-I single
      strand-specific nucleases, is thought to play a critical role in the salvage of
      purines, essential for the survival of these organisms. The 43-kDa 3'-NT/Nu was
      purified from L. donovani promastigotes and trypsin treated. Four of the released
      tryptic peptide fragments yielded amino-acid sequence information (Pept-1 to Pept
      4) which provided the basis for the preparation of oligonucleotide primers used
      for PCR amplification of an approx. 300-bp DNA fragment. This fragment was
      cloned, sequenced and used to probe a genomic L. donovani cosmid library.
      Nucleotide sequence analysis of a 4.5-kb SmaI fragment, isolated from a cosmid
      clone, revealed an open reading frame (ORF) of 1434 nt encoding a 477-amino-acid
      protein. Pept-1 to Pept-4 were mapped onto the ORF-deduced protein sequence.
      Peptides corresponding to Pept-1 to Pept-4 were synthesized and used to immunize
      rabbits. The resulting anti-peptide antibodies recognized the 43-kDa protein on
      Western blots and immunoprecipitated the native 3'-nucleotidase activity from L.
      donovani membrane extracts. Further, the ORF-deduced protein shared significant
      sequence identity with the S1 and P1 fungal nucleases of Aspergillus oryzae and
      Penicillium citrinum, respectively. Cumulatively, these results demonstrated that
      the ORF corresponded to a gene for the L. donovani 3'-nucleotidase/nuclease. In
      Northern blots a nucleotide probe specific for the 3'-NT/Nu gene hybridized to a
      single 2.5-kb messenger RNA. Results of Southern blot analyses were consistent
      with the 3'-NT/Nu being encoded by a single copy gene. These data constitute the
      first report of the gene for this unique trypanosomatid surface membrane enzyme.

PMID- 7630384
TI  - Characterization of two nuclear-encoded protein components of mitochondrial
      ribonucleoprotein complexes from Leishmania tarentolae.
AB  - Two mitochondrial proteins with molecular masses of 18 and 51 kDa were isolated
      from Leishmania tarentolae, and N-terminal amino-acid sequences were obtained.
      The cDNAs and genes encoding these proteins were cloned using RT-PCR. The
      proteins were identified as components of the previously characterized
      mitochondrial ribonucleoprotein complexes, T-Ia and T-VI, by comigration in
      native gels. The p18 and p51 genes contain 17 and 9-amino-acid N-terminal
      sequences, which are not present in the mature proteins and may represent
      cleavable mitochondrial targeting sequences. There are two identical p18 genes
      separated by 1.7 kb in tandem array and both are transcribed. The p18 amino-acid
      sequence is not similar to any sequence in the database. Antiserum to p18
      expressed in Escherichia coli reacts with the entire tubular mitochondrion. The
      p51 gene is single copy, and the amino-acid sequence is similar to mitochondrial
      aldehyde dehydrogenases from other organisms. The N-terminal amino-acid sequences
      of 71 and 62-kDa mitochondrial proteins which co-migrated in native gels with
      several other T-complexes were also obtained. The p71 sequence proved to be
      similar to hsp70 sequences from other organisms. The p62 sequence was identical
      to an hsp60 sequence from Trypanosoma brucei.

PMID- 7630385
TI  - Cloning of a Schistosoma japonicum gene encoding an antigen with homology to
      calreticulin.
AB  - A recombinant lambda gt11 clone, IVGS3, encoding part of a 55-kDa antigen was
      isolated from an adult Schistosoma japonicum cDNA library. The protein expressed
      by this clone was recognised strongly by serum from rats that had been vaccinated
      with irradiated cercariae (VrS) rendering them highly immune to a challenge
      infection. Antibodies in VrS which were specific for IVGS3 did not recognise
      adult worm antigens of S. mansoni, suggesting that the recombinant antigen
      contains species-specific epitopes, although IVGS3 was weakly recognised by rat
      serum raised against irradiated S. mansoni cercariae, indicating the presence of
      a related antigen in this species. A further clone, AM1(p), was obtained which,
      together with IVGS3 encompasses the entire coding region of the gene which has
      been called Sj55. Sequence analysis revealed similarities with murine
      calreticulin, a protein resident in the endoplasmic reticulum. As with murine
      calreticulin, Sj55 was shown to be a calcium-binding protein. Antigens with
      homologies to calreticulin have also been described in two other helminths, S.
      mansoni and Onchocerca volvulus.

PMID- 7630386
TI  - Organization and expression of the gene encoding an immunodominant repetitive
      antigen associated to the cytoskeleton of Trypanosoma cruzi.
AB  - We have studied the genomic organization and expression of the gene encoding a
      high molecular mass (300 kDa) repetitive antigen associated with the cytoskeleton
      of Trypanosoma cruzi. Protease digestion of the native protein, restriction
      analysis of genomic DNA and sequencing of genomic and cDNA clones indicated that
      most of the protein is built up by tandemly arranged, nearly identical repeats of
      68 amino acids. The gene size was estimated to be approx. 9.4 kb based on the
      sizes of the transcript and the native protein. The nucleotide sequence
      conservation among the repeats indicates that selective sequence homogenization,
      presumably through gene conversion, maintained the amino-acid sequence
      conservation. Two duplicated allelic forms of this gene were mapped in fragments
      of about 20 kb. In some strains an additional allele was located in a fragment of
      9.4 kb. Our results suggest that this repetitive antigen is a structural protein
      which could be involved in the attachment of the flagellum to the cell body.

PMID- 7630387
TI  - Natural selection on Plasmodium surface proteins.
AB  - Numbers of synonymous (ds) and nonsynonymous (dN) nucleotide substitutions per
      site were analysed in eight polymorphic Plasmodium genes: circumsporozoite
      protein gene (CSP), sporozoite surface protein 2 (thrombospondin related
      anonymous protein, TRAP), merozoite surface antigen 2 (MSA-2), apical membrane
      antigen 1 (PF83), liver-stage antigen-1 (LSA-1), knob-associated histidine-rich
      protein (KAHRP), ring-infected erythrocyte surface antigen (RESA) and S-antigen.
      In certain regions of genes coding for proteins of the sporozoite and merozoite
      surface (CSP, TRAP, MSA-2 and PF83), dN was significantly greater than dS. This
      unusual pattern of nucleotide substitution is indicative of positive Darwinian
      selection acting to promote diversity at the amino-acid level; thus our results
      suggest that the sporozoite and merozoite surface proteins are under positive
      selection, presumably exerted by the host immune system. No such pattern of
      substitution was observed on LSA-1, KAHRP, RESA, or S-antigen. Observed patterns
      of nucleotide substitution were not explicable by nucleotide content bias. G + C
      content in the 5' nonrepeat region of CSP in nine Plasmodium species was
      positively correlated with that in the 3' nonrepeat region; however, there was no
      relationship between G + C content and the ratio dS/dN in either CSP or a larger
      sample of all regions of all genes analysed.

PMID- 7630388
TI  - HIV scandal hits Bombay blood centre.

PMID- 7630389
TI  - Embryo research faces a renewed ban in US.

PMID- 7630390
TI  - Human genetics. Smart transcription factors.

PMID- 7630391
TI  - Cell cycle. Confirmational change.

PMID- 7630392
TI  - Biological rhythms. Resetting the circadian cycle.

PMID- 7630393
TI  - Opening up Ca2+ stores with InsP3.

PMID- 7630394
TI  - Opening up Ca2+ stores with InsP3.

PMID- 7630395
TI  - Oil biodegradation around roots.

PMID- 7630396
TI  - Protein molecules as computational elements in living cells.
AB  - Many proteins in living cells appear to have as their primary function the
      transfer and processing of information, rather than the chemical transformation
      of metabolic intermediates or the building of cellular structures. Such proteins
      are functionally linked through allosteric or other mechanisms into biochemical
      'circuits' that perform a variety of simple computational tasks including
      amplification, integration and information storage.

PMID- 7630397
TI  - Mechanism of CDK activation revealed by the structure of a cyclinA-CDK2 complex.
AB  - The crystal structure of the human cyclinA-cyclin-dependent kinase2 (CDK2)-ATP
      complex has been determined at 2.3 A resolution. CyclinA binds to one side of
      CDK2's catalytic cleft, inducing large conformational changes in its PSTAIRE
      helix and T-loop. These changes activate the kinase by realigning active site
      residues and relieving the steric blockade at the entrance of the catalytic
      cleft.

PMID- 7630398
TI  - Induction of epidermis and inhibition of neural fate by Bmp-4.
AB  - During gastrulation in vertebrates, ectodermal cells choose between two fates,
      neural and epidermal. The nervous system forms in response to signals from the
      Spemann organizer; ectoderm that does not receive these signals becomes
      epidermis. Unexpectedly, however, in Xenopus, neural tissue also forms when cell
      cell communication within the ectoderm is disrupted by cell dissociation or by
      antagonists of the growth factor activin. These observations suggest that
      epidermal specification depends on local signalling, by activin or a close
      relative, and that neural tissue forms when this communication is blocked. Here
      we report that bone morphogenesis protein 4 (Bmp-4), a relative of activin that
      is expressed in the embryo at the time of ectodermal fate determination, is a
      potent epidermal inducer and neural inhibitor, the first reported in any
      vertebrate. Activin can inhibit neuralization by inducing mesoderm, but does not
      induce epidermis. Moreover, the dominant-negative activin receptor, which
      stimulates neuralization when expressed in the embryo, blocks Bmp-4 in our assay.
      Our findings demonstrate that epidermal fate can be induced, and thus provide
      further evidence that neural specification is under inhibitory control in
      vertebrates.

PMID- 7630399
TI  - Regulation of neural induction by the Chd and Bmp-4 antagonistic patterning
      signals in Xenopus.
AB  - In Drosophila the amount of neurogenic ectoderm, from which the central nervous
      system (CNS) derives, is regulated by a dorsal-ventral system of positional
      information in which two secreted molecules of antagonistic functions,
      decapentaplegic (dpp) and short-gastrulation (sog), play fundamental roles. The
      vertebrate homologue of dpp is either bmp-4 or bmp-2 (ref. 5), and the homologue
      os sog is chd (s-chordin). In Xenopus the CNS is induced by signals emanating
      from the organizer, and two proteins secreted by the organizer, noggin and
      follistatin, have been shown to induce neural tissue in animal-cap assays. Here
      we report that Chd, another organizer-specific secreted factor, has neuralizing
      activity and that this activity can be antagonized by Bmp-4. Inhibition of the
      function of the endogenous Bmp-4 present in the animal cap also leads to neural
      differentiation. We suggest that conserved molecular mechanisms involving chd/sog
      and bmp-4/dpp gene products pattern the ectoderm in Xenopus and in Drosophila.

PMID- 7630400
TI  - Epithelial immaturity and multiorgan failure in mice lacking epidermal growth
      factor receptor.
AB  - Since the discovery that epidermal growth factor (EGF) can accelerate opening of
      the eyelids, the EGF receptor (EGF-R) has been extensively studied and is now
      considered to be a prototype tyrosine kinase receptor. Binding of EGF or of
      transforming growth factor-alpha (TGF-alpha) or other related factors activates
      the receptor and induces cell proliferation and differentiation. Although it is
      not found on haematopoietic cells, the EGF-R is widely expressed in mammals and
      has been implicated in various stages of embryonic development. Here we
      investigate the developmental and physiological roles of this receptor and its
      ligands by inactivating the gene encoding EGF-R. We find that EGF-R-/- mice
      survive for up to 8 days after birth and suffer from impaired epithelial
      development in several organs, including skin, lung and gastrointestinal tract.

PMID- 7630401
TI  - Effect of lesions in visual cortical area V4 on the recognition of transformed
      objects.
AB  - The primate visual system has a remarkable capability for recognizing objects
      irrespective of the multitude of images they form on the retinal surface by
      virtue of changes in size, perspective, contrast, colour and partial obstruction
      by other stimuli in the visual scene. There is increasing evidence that this
      remarkable capacity is brought about by processes that occur earlier in the
      visual system than had previously been thought. Here I show that after ablation
      of area V4 in the rhesus monkey, major deficits arise in the recognition of
      objects that have been transformed in size, in the degree of occlusion, and in
      the amount of contour information provided. The ability to detect these objects
      when presented individually was unaffected by these lesions.

PMID- 7630402
TI  - Neural regulation of thermotaxis in Caenorhabditis elegans.
AB  - Thermal stimulus is an important environmental factor influencing animal
      behaviour. However, the mechanisms underlying thermosensation and thermal
      adaptation are poorly understood. The nematode Caenorhabditis elegans can sense a
      range of environmental temperatures and migrate towards the cultivation
      temperature on a thermal gradient. This modifiable thermotactic response provides
      an ideal system for studying the cellular and molecular processes involved in
      thermosensation and thermal information storage. We have identified neurons
      critical for thermotaxis by killing individual cells in live animals. The results
      indicate that an amphid sensory neuron, AFD, is a major thermosensory neuron.
      Some of the genetically defined cryophilic and thermophilic mutant phenotypes
      were mimicked when amphid interneurons AIY and AIZ, respectively, were killed,
      indicating that AIY is responsible for thermophilic movement and AIZ for
      cryophilic movement. We propose a neural model in which regulation of the
      activities of the two interneurons in opposite directions, depending on the
      cultivation temperature, is essential for thermotaxis.

PMID- 7630403
TI  - Rubinstein-Taybi syndrome caused by mutations in the transcriptional co-activator
      CBP.
AB  - The Rubinstein-Taybi syndrome (RTS) is a well-defined syndrome with facial
      abnormalities, broad thumbs, broad big toes and mental retardation as the main
      clinical features. Many patients with RTS have been shown to have breakpoints in,
      and microdeletions of, chromosome 16p13.3 (refs 4-8). Here we report that all
      these breakpoints are restricted to a region that contains the gene for the human
      CREB binding protein (CBP), a nuclear protein participating as a co-activator in
      cyclic-AMP-regulated gene expression. We show that RTS results not only from
      gross chromosomal rearrangements of chromosome 16p, but also from point mutations
      in the CBP gene itself. Because the patients are heterozygous for the mutations,
      we propose that the loss of one functional copy of the CBP gene underlies the
      developmental abnormalities in RTS and possibly the propensity for malignancy.

PMID- 7630404
TI  - Allelic exclusion of Ly49-family genes encoding class I MHC-specific receptors on
      NK cells.
AB  - An important feature of natural killer (NK) cell activity is the lysis of cells
      that have extinguished expression of some or all class I major histocompatibility
      (MHC) molecules. Accordingly, the Ly49A NK-cell antigen receptor has been shown
      to deliver an inhibitory signal to NK cells on encounter with Dd or Dk class I
      MHC on target cells. Ly49A belongs to a family of eight or more highly related,
      tightly linked genes. Expression of Ly49A and Ly49C, another member of the Ly49
      family with distinct MHC specificity, define subpopulations of NK cells that are
      only partly overlapping. The mechanisms regulating the expression of LY49 family
      members are unknown. We show here that the Ly49A and Ly49C NK-cell receptors are
      each subject to allelic exclusion. Because Ly49 genes are not thought to undergo
      DNA rearrangement, allelic exclusion of Ly49 genes could involve a mechanism
      distinct from that used by B and T lymphocytes and is likely to play an important
      role in the genesis of a putative NK-cell repertoire specific for class I
      molecules.

PMID- 7630405
TI  - Requirement for tyrosine phosphorylation of Cdk4 in G1 arrest induced by
      ultraviolet irradiation.
AB  - Exposure to ultraviolet light arrests the function of mammalian fibroblasts in
      the G1 phase of the cell cycle, as well as the S and G2 phases. Although p21, an
      inhibitor of cyclin-dependent kinase (Cdk) that is induced by DNA damage may
      partly account for the arrest in G1 (ref. 1), the mechanism is little understood.
      Here we show that tyrosine phosphorylation of Cdk4 is required for this arrest.
      In rat fibroblast, Cdk4 is tyrosine-phosphorylated during G1 progression, and its
      dephosphorylation is required for S phase. When cells are ultraviolet-irradiated,
      their arrest in G1 is accompanied by an increase in phosphorylation level.
      Conversely, cells expressing unphosphorylatable Cdk4F17 fail to arrest in G1, and
      suffer significantly elevated chromosomal aberrations and cell death.

PMID- 7630406
TI  - Crystal structure of a replication fork single-stranded DNA binding protein (T4
      gp32) complexed to DNA.
AB  - The single-stranded DNA (ssDNA) binding protein gp32 from bacteriophage T4 is
      essential for T4 DNA replication, recombination and repair. In vivo gp32 binds
      ssDNA as the replication fork advances and stimulates replisome processivity and
      accuracy by a factor of several hundred. Gp32 binding affects nearly every major
      aspect of DNA metabolism. Among its important functions are: (1) configuring
      ssDNA templates for efficient use by the replisome including DNA polymerase; (2)
      melting out adventitious secondary structures; (3) protecting exposed ssDNA from
      nucleases; and (4) facilitating homologous recombination by binding ssDNA during
      strand displacement. We have determined the crystal structure of the gp32 DNA
      binding domain complexed to ssDNA at 2.2 A resolution. The ssDNA binding cleft
      comprises regions from three structural subdomains and includes a positively
      charged surface that runs parallel to a series of hydrophobic pockets formed by
      clusters of aromatic side chains. Although only weak electron density is seen for
      the ssDNA, it indicates that the phosphate backbone contacts an electropositive
      cleft of the protein, placing the bases in contact with the hydrophobic pockets.
      The DNA mobility implied by the weak electron density may reflect the role of
      gp32 as a sequence-independent ssDNA chaperone allowing the largely unstructured
      ssDNA to slide freely through the cleft.

PMID- 7630407
TI  - Embargo system under siege on Wall St over obesity gene.

PMID- 7630408
TI  - MRC cuts funding of alpha-rated projects.

PMID- 7630409
TI  - Apoptosis again.

PMID- 7630410
TI  - Cerebral malaria.

PMID- 7630411
TI  - Birth dates.

PMID- 7630412
TI  - Protein synthesis. Ins and outs of the ribosome.

PMID- 7630413
TI  - Localization of active zones.

PMID- 7630414
TI  - Runaway telomere elongation caused by telomerase RNA gene mutations.
AB  - The ribonucleoprotein enzyme telomerase adds telomeric DNA onto chromosome ends
      and is normally regulated so that telomeric DNA lengths are kept within defined
      bounds. In the telomerase RNA gene from the yeast Kluyveromyces lactis, specific
      mutations that alter telomeric DNA sequences result in telomeres elongating to up
      to 100 times their normal length and impair cell growth. Some mutations cause
      immediate elongation whereas others behave like genetic time bombs, causing
      elongation only after a latent period of hundreds of generations.

PMID- 7630415
TI  - A trade-off-invariant life-history rule for optimal offspring size.
AB  - Optimization models have been widely and successfully used in evolutionary
      ecology to predict the attributes of organisms. Most such models maximize
      darwinian fitness (or a component of fitness) in the face of trade-offs and
      constraints; the numerical results usually depend on the exact form of the trade
      offs/constraints. Here we report the first (to our knowledge) numerical optimum
      for life-history evolution which is independent of the details of the underlying
      trade-off, for a large array for trade-off forms. The rule is that at small
      litter sizes, the range in offspring size is inversely proportional to the size
      of the litter. Details of the offspring-survival/offspring-size trade-off set the
      value of the proportionality constant, but the -1 exponent, the inverse
      proportionality itself, is universal. Studies of life histories have yielded many
      empirical examples of universality for various scaling exponents (for example,
      adult lifespan scales as approximately 0.25 with adult body mass within many
      taxa); this is an example of the numerical value of an exponent (here -1)
      emerging from a life-history model as independent of all but a few general
      features of the underlying economic structure.

PMID- 7630416
TI  - Hox genes and the diversification of insect and crustacean body plans.
AB  - Crustaceans and insects share a common origin of segmentation, but the
      specialization of trunk segments appears to have arisen independently in insects
      and various crustacean subgroups. Such macroevolutionary changes in body
      architecture may be investigated by comparative studies of conserved genetic
      markers. The Hox genes are well suited for this purpose, as they determine
      positional identity along the body axis in a wide range of animals. Here we
      examine the expression of four Hox genes in the branchiopod crustacean Artemia
      franciscana, and compare this with Hox expression patterns from insects. In
      Artemia the three 'trunk' genes Antp, Ubx and abdA are expressed in largely
      overlapping domains in the uniform thoracic region, whereas in insects they
      specify distinct segment types within the thorax and abdomen. Our comparisons
      suggest a multistep process for the diversification of these Hox gene functions,
      involving early differences in tissue specificity and the later acquisition of a
      role in defining segmental differences within the trunk. We propose that the
      branchiopod thorax may be homologous to the entire pregenital (thoracic and
      abdominal) region of the insect trunk.

PMID- 7630417
TI  - Distinguishable functions for engrailed and invected in anterior-posterior
      patterning in the Drosophila wing.
AB  - Subdivision of the limb primordia into compartments initiates pattern formation
      in the developing limbs. Interaction between distinctly specific cells in
      adjacent compartments leads to localized expression of the secreted signalling
      molecules Wingless (Wg) or Decapentaplegic (Dpp), which in turn organize pattern
      and control growth of the limbs. The homeobox gene engrailed has been implicated
      in specification of posterior cell fate, whereas the LIM/homeobox gene, apterous,
      specifies dorsal fate. Removing apterous activity causes a complete
      transformation from dorsal to ventral fate and leads to the formation of an
      ectopic dorsal-ventral boundary organizer. By contrast, removing engrailed
      activity causes incomplete morphological transformation from posterior to
      anterior fate in the wing, and fails to produce an ectopic anterior-posterior
      organizer (reviewed in ref.2). Complete transformation can only be effected by
      simultaneously eliminating activity of engrailed and its homologue invected. Here
      we show that invected functions principally to specify posterior cell fate. Thus
      establishment of the anterior-posterior organizer and control of compartment
      identity are genetically distinguishable, and invected may perform a discrete
      subset of functions previously ascribed to engrailed.

PMID- 7630418
TI  - Specification of neuroblast identity in the Drosophila embryonic central nervous
      system by gooseberry-distal.
AB  - The Drosophila central nervous system develops from a segmentally reiterated
      array of 30 unique neural precursors, called neuroblasts. Each neuroblast goes
      through a stereotyped cell lineage to produce an invariant clone of neural
      progeny. It is critical to identify the genes that specify neuroblast identity as
      these genes control the time of formation, gene expression profile, and cell
      lineage characteristics of each neuroblast. Here we show that the Pax-type
      gooseberry-distal gene specifies row 5 neuroblast identity. Initially, four rows
      of neuroblasts form per segment (1, 3, 5, 7) and gooseberry-distal is expressed
      in row 5 neuroblasts. By using 10 molecular markers, and by following the number
      and orientation of neuroblast divisions, we show that lack of gooseberry-distal
      transforms row 5 neuroblasts into row 3 neuroblasts, whereas ubiquitous
      gooseberry-distal generates the reciprocal transformation. Thus, gooseberry
      distal is necessary and sufficient to specify row 5 neuroblast identity
      autonomously. The 10 genes coordinately regulated by gooseberry-distal are prime
      candidates for controlling specific aspects of neuroblast identity.

PMID- 7630419
TI  - Resistance to herpes stromal keratitis conferred by an IgG2a-derived peptide.
AB  - Not all peripheral tissue antigens enter the thymus and it is unclear how the
      immune system remains tolerant to this class of self antigen. As tolerance to
      self peptides can generate gaps in the T-cell repertoire for cross-reactive
      foreign antigens, we investigated whether this mechanism might also diminish
      autoimmune reactions to similar peptides expressed by peripheral tissues. Herpes
      stromal keratitis (HSK) is a virally induced autoimmune reaction against corneal
      tissues mediated by T cells, and is a leading cause of human blindness.
      Resistance to HSK in mice is associated with allotypic variation in
      immunoglobulin genes, possibly because circulating immunoglobin-derived peptides
      can cross-tolerize T cells specific for corneal tissue autoantigens. Here we show
      that HSK is mediated by T-cell clones specific for corneal self antigens which
      also recognize an allotype-bearing peptide derived from IgG2a, and that exposure
      of HSK-susceptible mice to a soluble form of this peptide confers resistance to
      HSK. Shared expression of peptide subsequences between sequestered tissue
      proteins and circulating proteins may be important for maintenance of self
      tolerance and prevention of autoimmunity.

PMID- 7630420
TI  - First experimental transmission of fatal familial insomnia.
AB  - Originally described by Lugaresi et al. in 1986 (ref. 1), fatal familial insomnia
      (FFI) is a rare inherited neurological disease characterized by the subacute
      progression of intractable insomnia and other autonomic abnormalities, cerebellar
      and pyramidal signs, myoclonus and dementia; neuropathologically, the major
      feature is severe neuronal loss with associated gliosis in the ventral and
      mediodorsal thalamic nuclei. The disease has been related to the group of
      spongiform encephalopathies by virtue of the presence of low levels of proteinase
      resistant amyloid protein (PrPres) in the brain, and of a pathogenic single
      allele mutation at codon 178 of the PRNP gene that encodes PrPres (refs 2, 5).
      Here we report the successful transmission of the disease to experimental
      animals, placing FFI within the group of infectious cerebral amyloidoses.

PMID- 7630422
TI  - A model of protein synthesis based on cryo-electron microscopy of the E. coli
      ribosome.
AB  - The ribosome is formed by assembly of proteins and nucleic acids, and synthesizes
      proteins according to genetic instructions in all organisms. Many of the
      biochemical steps of this fundamental process are known, but a detailed
      understanding requires a well-defined structural model of the ribosome. Electron
      microscopy combined with image reconstruction of two-dimensional crystals or
      single ribosomes has been the most promising technique, but the resolution of the
      resulting models has been insufficient. Here we report a 25-A reconstruction of
      the ribosome from Escherichia coli, obtained by combining 4,300 projections of
      ice-embedded single particles. Our new reconstruction reveals a channel in the
      small ribosomal subunit and a bifurcating tunnel in the large subunit which may
      constitute pathways for the incoming message and the nascent polypeptide chain,
      respectively. Based on these new findings, a three-dimensional model of the basic
      framework of protein synthesis is presented.

PMID- 7630421
TI  - Essential role for ZAP-70 in both positive and negative selection of thymocytes.
AB  - During thymic development, T cells that can recognize foreign antigen in
      association with self major histocompatibility complex (MHC) are selected for
      survival (positive selection) and autoreactive T cells are eliminated (negative
      selection). Both of these selective events are mediated by interaction between
      the T-cell receptor (TCR) and the peptide-MHC complex. But the signalling
      pathways that lead to cell survival or to cell death are still unclear. ZAP-70 is
      a protein tyrosine kinase (PTK) that is associated with the TCR signalling
      subunits (CD3 and zeta) and is expressed in T cells and natural killer cells. It
      has been shown that ZAP-70 plays a crucial role in T-cell activation and
      development. Here we show that mice lacking ZAP-70 had neither CD4 nor CD8 single
      positive T cells, but human ZAP-70 reconstituted both CD4 and CD8 single-positive
      populations. Moreover, ZAP-70-/- thymocytes were not deleted by peptide antigens.
      Natural killer cell function was intact in the absence of ZAP-70. These data
      suggest that ZAP-70 is a central signalling molecule during thymic selection for
      CD4 and CD8 lineage.

PMID- 7630423
TI  - Sequestration of the membrane-targeting myristoyl group of recoverin in the
      calcium-free state.
AB  - Recoverin, a retinal calcium-binding protein of relative molecular mass (M(r))
      23K, participates in the recovery phase of visual excitation and in adaptation to
      background light. The Ca(2+)-bound form of recoverin prolongs the photoresponse,
      probably by blocking phosphorylation of photoexcited rhodopsin. Retinal recoverin
      contains a covalently attached myristoyl group or related acyl group at its amino
      terminus and two Ca(2+)-binding sites. Ca2+ binding to myristoylated, but not
      unmyristoylated, recoverin induces its translocation to bilayer membranes,
      indicating that the myristoyl group is essential to the read-out of calcium
      signals (calcium-myristoyl switch). Here we present the solution structure of
      Ca(2+)-free, myristoylated recombinant recoverin obtained by heteronuclear
      multidimensional NMR spectroscopy. The myristoyl group is sequestered in a deep
      hydrophobic pocket formed by many aromatic and other hydrophobic residues from
      five flanking helices.

PMID- 7630424
TI  - Analysis of receptor-G protein interactions in permeabilized cells.
AB  - Receptor-induced binding of the stable GTP analogue, guanosine 5'-[gamma
      thio]triphosphate (GTP [gamma S]), to guanine nucleotide-binding regulatory
      proteins (G proteins) was measured in various permeabilized cells. In myeloid
      differentiated human leukemia (HL-60) cells, permeabilized with either digitonin,
      streptolysin O or Staphylococcus aureus alpha-toxin, binding of GTP[gamma S]
      induced by three distinct chemoattractant receptors was observed. The extent of
      receptor-stimulated GTP[gamma S] binding (maximally about 2-fold) was independent
      of the type of permeabilizing agent used. In human erythroleukemia cells
      permeabilized with digitonin, agonist activation of thrombin and neuropeptide Y
      receptors increased GTP[gamma S] binding by 1.8- and 1.5-fold, respectively.
      Finally, in adherently grown human embryonic kidney cells permeabilized with
      digitonin, activation of the stably expressed human muscarinic m3 receptor
      increased GTP[gamma S] binding by about 1.6-fold. In digitonin-permeabilized HL
      60 cells, a quantitative analysis of formyl peptide receptors and interacting G
      proteins was performed. About 50,000 formyl peptide receptors per cell were
      detected. Agonist binding to these receptors was fully sensitive to regulation by
      guanine nucleotides and pertussis toxin. The number of high-affinity GTP[gamma S]
      binding sites, most likely representing heterotrimeric G proteins, was calculated
      to be about 670,000 per cell. Stimulation of formyl peptide receptors led to the
      activation of about 130,000 of high-affinity GTP[gamma S] binding sites,
      indicating a ratio of about three activated G proteins per one agonist-activated
      receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7630425
TI  - Effects of methysticin on three different models of seizure like events studied
      in rat hippocampal and entorhinal cortex slices.
AB  - Methysticin is one of the constituents of Piper methysticum which possesses
      anticonvulsant and neuroprotective properties. Its effects on different in vitro
      seizure models were tested using extracellular recordings in rat temporal cortex
      slices containing the hippocampus and the entorhinal cortex. Elevating [K+]0
      induced seizure-like events with tonic and clonic electrographic phases in area
      CA1. Lowering [Ca2+]0 caused recurrent seizure like episodes with large negative
      field potential shifts. Lowering Mg2+ induced short recurrent discharges in area
      CA3 and CA1 while ictaform events lasting for many seconds were induced in the
      subiculum, entorhinal and temporal neocortex. In the hippocampus the activity
      stayed stable over a number of hours. In contrast, the ictaform events in the
      subiculum, entorhinal and temporal cortex changed their characteristics after one
      to two hours to late recurrent discharges. In a concentration-range from 10 to
      100 microM methysticin reversibly blocked all these types of epileptiform
      activity. Decreases in [Ca2+]0 and associated slow field potentials evoked by
      repetitive stimulation of the stratum radiatum or the alveus remained almost
      unaffected by methysticin. A paired pulse stimulus paradigm used to test for
      effects of methysticin on synaptically evoked transient field potentials in
      normal medium revealed interference with mechanisms involved in frequency
      potentiation. While responses to alvear stimulation were largely unaffected, the
      responses to a paired pulse stimulus to stratum radiatum were depressed over the
      whole range of tested stimulus intervals. The findings suggest that methysticin
      has effects on different patterns of epileptiform activity possibly by
      interfering with processes responsible for frequency potentiation.

PMID- 7630426
TI  - An autoradiographic study comparing the interactions of 3 alpha-OH-5 alpha
      pregnan-20-one, pregnenolone sulfate and pentobarbital with [3S]-TBPS binding
      sites and their modulation by GABA in different structures of the rat brain.
AB  - Using quantitative autoradiography, we have studied the distribution of the [35S]
      TBPS binding sites of the GABA-A receptor complex in various structures of the
      rat brain. High densities of binding sites were observed in layer IV of the
      cerebral cortex, in the globus pallidus, and in the thalamus. Intermediate
      densities of binding sites were observed in superficial and deep layers of the
      cerebral cortex, in the dentate gyrus and in the hippocampus. For all of these
      structures, the interactions of 3 alpha-OH-5 alpha-pregnan-20-one (3 alpha 5
      alpha P), pregnenolone sulfate (PS), and pentobarbital with [35S]-TBPS binding,
      in the presence or the absence of GABA were studied. In the absence of GABA, IC50
      values for the inhibition of [35S]-TBPS binding were 10(-6) M for 3 alpha 5 alpha
      P and 10(-4) M for PS and pentobarbital in all of the brain regions studied. In
      the presence of GABA (5 x 10(-6) M), IC50 values were decreased by one order of
      magnitude for 3 alpha 5 alpha P, PS, and pentobarbital in all structures studied
      except layer IV of the cortex, where the IC50 value for PS was more markedly
      decreased (up to two orders of magnitude). By contrast, IC50 values for
      picrotoxin and TBPS to inhibit [35S]-TBPS binding were 10(-7) M and 10(-8) M,
      respectively, in the presence or absence of GABA.

PMID- 7630428
TI  - In vitro and in vivo activity of 1-(1-naphthyl)piperazine at terminal 5-HT
      autoreceptors in guinea-pig brain.
AB  - The effect of 1-(1-naphthyl)piperazine (NP) on the 5-HT terminal autoreceptor
      modulating 5-HT release was investigated in vitro and in vivo. In vitro 5-HT
      release was measured in slices of guinea-pig substantia nigra and hypothalamus
      prelabelled with 3H-5-HT, superfused with Krebs solution and depolarized
      electrically. NP, at 0.1 and 1 mumol/l, did not modify the calcium-dependent
      release of 3H-5-HT elicited by electrical stimulation using a frequency of 5 Hz,
      however at 0.1 mumol/l NP shifted to the right the inhibition curve of the non
      selective autoreceptor agonist, 5-carboxamidotryptamine, in both regions. In
      hypothalamus when using lower frequencies (1 Hz or 0.2 Hz) or under pseudo-one
      pulse stimulation, NP decreased the release of 3H-5-HT at 1 mumol/l. In vivo
      microdialysis was used to measure extracellular levels of endogenous 5-HT in the
      substantia nigra of freely moving guinea-pigs. The endogenous release of 5-HT was
      tetrodotoxin (TTX)-sensitive, indicating a neuronal origin of this efflux. NP,
      administered through the microdialysis probe (1-100 mumol/l), increased the
      levels of extracellular 5-HT in concentration-dependent and TTX-sensitive manner.
      These results suggest that in vitro NP acts as a 5-HT autoreceptor partial
      (ant)agonist in the substantia nigra and hypothalamus of guinea-pigs, and as a
      full antagonist in vivo. However, NP administered systemically at 10 mg/kg i.p.,
      did not modify the levels of extracellular 5-HT in the substantia nigra. This
      lack of systemic effect of NP probably results from its interaction at other
      receptors that modify 5-HT neurotransmission.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7630427
TI  - Role of N-methyl-D-aspartic acid and cholecystokinin receptors in apomorphine
      induced aggressive behaviour in rats.
AB  - We studied the aggressive behaviour induced by repeated treatment with
      apomorphine, a dopamine agonist (0.5 mg/kg s.c. twice daily, 10 days), in rats.
      The first signs of defensive aggressiveness appeared on the third day of
      apomorphine treatment and were generally seen on the 7th day. Aggressiveness
      induced by a challenge dose of apomorphine (0.5 mg/kg s.c.) on the 11th day was
      antagonized by haloperidol (0.05 and 0.1 mg/kg i.p.) and clozapine (10 mg/kg
      i.p.). An antagonist of N-methyl-D-aspartate (NMDA)-gated channels, dizocilpine
      (MK-801), also blocked the aggressive behaviour at 0.25 and 0.5 mg/kg i.p. but
      caused ataxia. When dizocilpine (0.25 mg/kg i.p.) and apomorphine were
      coadministered for 10 days, aggressive behaviour did not develop. At 0.025 mg/kg
      i.p., dizocilpine even accelerated the appearance of apomorphine-induced
      aggressive behaviour, which manifested on the 3rd day in all rats. In a separate
      study, a 7-day treatment with dizocilpine (0.25-1 mg/kg i.p.) of rats, sensitized
      by a prior 10-day apomorphine treatment, did not reverse the established
      aggressive behaviour. The coadministration of apomorphine and cholecystokinin
      (CCK) -A or -B antagonists, devazepide or L-365,260 (0.01-2.5 mg/kg i.p.)
      respectively, neither affected development of apomorphine-induced aggressive
      behaviour nor intensity of aggressiveness in the sensitized rats. In binding
      studies neither density nor affinity of striatal dopamine D2 receptors was
      changed by acute or chronic apomorphine treatment. The number of [3H]pCCK-8
      binding sites in the frontal cortex increased already after a single injection of
      apomorphine.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7630429
TI  - Mechanisms of the contractile effects of flosequinoxan.
AB  - In guinea-pig papillary muscles the positive inotropic effect of flosequinoxan
      (BTS) starting at 100 mumol/l amounted to 287.6 +/- 34.2% at 300 mumol/l without
      any effects on time to peak tension (103.9 +/- 2%) and relaxation time (107.1 +/-
      6.7% of predrug value, respectively). 10 mumol/l carbachol attenuated the
      positive inotropic effect of 300 mumol/l to 166.5 +/- 11.6% (n = 10). The
      phosphorylation state of the inhibitory subunit of troponin (TnI) and
      phospholamban (PLB) in [32P]-labeled guinea-pig ventricular myocytes was
      increased starting at 100 mumol/l amounting to 142.5 +/- 12.6% and 130.9 +/- 2.2%
      at 300 mumol/l, respectively (n = 5). Furthermore, BTS (300 mumol/l) decreased
      phosphorylase phosphatase activity by 23.1%. It is concluded that the contractile
      effects of BTS are accompanied by enhanced phosphorylation of regulatory proteins
      which could in part be due to inhibition of phosphorylase phosphatase activity.

PMID- 7630431
TI  - Evidence for saturation of catechol-O-methyltransferase by low concentrations of
      noradrenaline in perfused lungs of rats.
AB  - Previous studies on the pulmonary removal and metabolism of catecholamines in rat
      lungs have shown that, when the lungs are perfused with a low concentration (1
      nmol/l) of noradrenaline, the amine is metabolized by catechol-O
      methyltransferase (COMT) and monoamine oxidase (MAO), but is predominantly O
      methylated, and the activities of COMT and MAO are 0.357 min-1 and 0.186 min-1,
      respectively. The aim of the present study was to examine the changes in the
      metabolic profile of noradrenaline in rat lungs over a range of concentrations,
      and to examine the kinetics of the pulmonary O-methylation of noradrenaline and
      adrenaline. In isolated lungs perfused with 3H-noradrenaline, there was a
      progressive decrease in the proportion of O-methylated metabolites and a
      corresponding increase in the proportion of deaminated metabolites, as the
      noradrenaline concentration in the perfusion solution was increased from 1 to 10
      to 100 to 1000 nmol/l. Experiments designed to determine the rate of uptake of
      noradrenaline in lungs perfused with 1 nmol/l 3H-noradrenaline, under conditions
      of MAO inhibited, COMT inhibited and COMT and MAO inhibited, showed that the
      results were compatible with co-existence of COMT and MAO in the pulmonary
      endothelial cells. Hence, it appeared that the changing metabolic profile with
      amine concentration in the previous series of experiments was not due to
      saturation of noradrenaline uptake into cells that contained COMT but not
      MAO.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7630430
TI  - Hypertrophic cardiomyopathy: a desensitized cardiac beta-adrenergic system in the
      presence of normal plasma catecholamine concentrations.
AB  - Only few data are available concerning the biochemical and functional state of
      the beta-adrenergic system in hypertrophied human myocardium. The present study
      was to investigate the myocardial beta-adrenergic signal transduction system in
      hypertrophic obstructive cardiomyopathy (HOCM). Thin myocardial strips were
      prepared from surgically excised, septal myocardium from 7 patients with HOCM and
      their force of contraction was measured in vitro. The positive inotropic effects
      of calcium and dihydro-ouabain, both acting independently of beta-adrenoceptors
      and cAMP, were similar in these preparations to those, previously published, seen
      with nonfailing myocardium. In contrast, the beta-adrenoceptor agonist
      isoprenaline and the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine
      (IBMX) had reduced positive inotropic effects. Their EC50-values were about 10
      fold higher than the respective EC50-values published for nonfailing myocardium.
      The positive inotropic potencies of isoprenaline and IBMX were reduced in HOCM by
      as much as they were in the additionally investigated myocardium from 6 patients
      with severe mitral regurgitation (MR, NYHA III). In order to clarify whether the
      functional alterations are related to changes in the beta-adrenoceptors, beta
      adrenoceptor density and beta 1: beta 2-adrenoceptor subtype distribution were
      determined in the same myocardium using 125I-Iodocyanopindolol saturation
      binding. Myocardial beta-adrenoceptor density was reduced to 68% in HOCM and to
      56% in MR compared to nonfailing myocardium controls (NF: 64.8 +/- 6.5 fmol/mg
      protein). In HOCM, this reduction was due to a selective down regulation of beta
      1-adrenoceptors (24.9 +/- 3.7 fmol/mg protein vs NF: 46.4 +/- 6.8 fmol/mg
      protein, P < 0.05), whereas beta 2-adrenoceptor density was unchanged (19.0 +/-
      1.9 fmol/mg protein vs NF: 18.4 +/- 3.3 fmol/mg protein, n.s.). In MR both beta
      adrenoceptor subtypes were reduced (beta 1: 26.9 +/- 1.4 fmol/mg protein, beta 2:
      9.6 +/- 1.7 fmol/mg protein; both P < 0.05 vs NF). Electrochemically determined
      plasma catecholamine levels were elevated in MR. However, plasma catecholamine
      levels were normal or slightly below normal in HOCM. In summary, myocardial beta
      adrenoceptors are downregulated and their function is impaired in HOCM. This
      desensitization is not caused by a negative feedback regulation due to increased
      plasma catecholamines. The present results show that the desensitizations of the
      beta-adrenergic system associated with HOCM has characteristics that indicate a
      major deviation in its development from that of the beta-adrenergic
      desensitization previously described to occur in congestive heart failure.

PMID- 7630432
TI  - Characterization of furoxans as a new class of tolerance-resistant
      nitrovasodilators.
AB  - The vasodilator effects of C92-4609 (4-hydroxymethyl-furoxan-3-carboxamide, CAS
      1609), C92-4678(4-phenyl-furoxan-3-carboxylic acid (pyridyl-3-yl-methyl)-amide),
      C92-4679 (3-phenyl-furoxan-4-carboxylic acid (pyridyl-3-yl-methyl)-amide) and C93
      4759 (3-hydroxymethyl-furoxan-4-carboxamide) were studied in the isolated rabbit
      femoral artery and jugular vein. All furoxans were potent vasodilators in the
      femoral artery (EC50 0.1-50 microM), while they were less potent in the jugular
      vein by at least one order of magnitude. Apart from C92-4679, the vasodilatory
      potency of the furoxans correlated well with their nitric oxide (NO)-releasing
      capacity which was estimated both by stimulation of purified soluble guanylyl
      cyclase activity and electron spin resonance spectroscopy with a trapping agent
      for NO. The hypothesis that furoxans stimulate soluble guanylyl cyclase in the
      smooth muscle by spontaneously releasing NO was supported by the marked
      attenuation of their vasodilator effect in the presence of oxyhaemoglobin (10
      microM) or following treatment with methylene blue (30 microM). In contrast to
      earlier findings, NO release from these furoxans was not thiol-dependent, as
      demonstrated for C92-4609, the relaxant effect of which in the femoral artery was
      not altered in the presence of N-acetyl-L-cysteine (1 mM). Moreover the KCa+
      channel inhibitor, tetrabutylammonium (3 mM), but not the KATP+ channel
      inhibitor, glibenclamide (3 microM), significantly attenuated the dilator
      response to C92-4679 in the femoral artery. Pretreatment of these segments with
      the cytochrome P450 inhibitor, SKF525a (30 microM), also reduced the C92-4679
      induced relaxation in this vascular bed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7630434
TI  - Congress mulls over Medicare cuts: will the ESRD program be touched?

PMID- 7630435
TI  - The warmth amidst the first Winter Transplant Games took the chill out of the
      Aspen Air.

PMID- 7630433
TI  - Inhibition by interleukin-1 beta of noradrenaline release in rat spleen:
      involvement of lymphocytes, NO and opioid receptors.
AB  - Effects of indomethacin, N omega-nitro-L-arginine (NNA) and naloxone, and of
      pretreatment with cyclophosphamide (CY), on the interleukin (IL)-1 beta induced
      inhibition of exocytotic noradrenaline release were investigated in the isolated,
      vascularly perfused spleen of the rat. Neurotransmitter release was evoked by
      perivascular electrical stimulation (4 Hz) and the overflow of endogenous
      noradrenaline was determined by HPLC with electrochemical detection. Perfusion of
      the spleen with Tyrode's solution containing IL-1 beta (100 pg/ml) for 90 min
      caused an inhibition of the stimulation-evoked noradrenaline overflow which
      persisted for at least 20 min after washout of the IL. The evoked overflow was
      reduced in the presence of NNA 30 mumol/l, but remained unaffected by
      indomethacin 3 mumol/l, naloxone 0.1 mumol/l or treatment of the rats with CY
      (250 mg/kg). The opioid agonist etorphine 10 mumol/l inhibited the evoked
      overflow of noradrenaline and this effect was prevented by naloxone 0.1 mumol/l.
      The inhibition of evoked overflow by IL-1 beta was not affected by indomethacin
      but was reduced or even prevented in the presence of NNA or naloxone, or after
      lymphocyte depletion of spleens by CY. The results are compatible with the idea
      that in the rat spleen exocytotic noradrenaline release is accompanied by a
      concomitant secretion of a nitric oxide (NO)-like compound which, in turn,
      reinforces noradrenaline release, and that the release can be inhibited via
      prejunctional opioid receptors. The IL-1 beta induced inhibition of evoked
      release appears to be a complex process which involves as one of many steps a
      decrease of the facilitatory NO-like compound and the release of endogenous
      opioids probably from spleen lymphocytes.

PMID- 7630437
TI  - Florida support group helps to ease fears of transplantation.

PMID- 7630436
TI  - Providers beware: HMOs may control your destiny.

PMID- 7630438
TI  - Patient's perspective: exercise and a positive attitude help dialysis patients to
      thrive.

PMID- 7630439
TI  - IDN core competencies: nursing's role.

PMID- 7630440
TI  - An interview with Linda D'Angelo. Interview by Connie R. Curran.
AB  - Linda D'Angelo, MBA, MSN, RN,C, is president, American Academy of Ambulatory Care
      Nursing, Pitman, NJ, and associate administrator, Carle Clinic Association,
      Urbana, IL. In this interview, Ms. D'Angelo discusses the key issues facing
      ambulatory care and ambulatory care nursing.

PMID- 7630441
TI  - Cultural diversity and conflict in the health care workplace.
AB  - Cultural diversity issues affect the health care workplace and nursing practice.
      The Lowenstein-Glanville conflict model can be used for assessing and intervening
      in racial and status conflict in hospital settings. Implications for nursing
      practice include recognizing that cultural diversity will continue to grow in the
      health care workplace. Nurses must increase sensitivity, become aware of cultural
      nuances and issues, and make cultural assessment a routine part of their
      assessment and planning, not only for patient care, but also with their co
      workers and subordinates.

PMID- 7630442
TI  - Predicting hospital length of stay in elderly patients with congestive heart
      failure.
AB  - The purpose of this study was to determine the variables, available at the time
      of hospital admission, that are associated with length of hospitalization. A
      second objective was to explore the extent to which patient functional status, an
      area of great concern to nursing, explains length of hospitalization. Severity of
      illness and functional status emerged as significant predictors of length of
      hospital stay.

PMID- 7630443
TI  - Predictors of absenteeism among hospital staff nurses.
AB  - An organizational dynamics paradigm is examined for effectiveness in predicting
      absenteeism among staff RNs in four hospitals. Different predictor variables were
      important within each hospital. Discussion is focused on the manager role and
      organizational policies related to criteria for excessive absence, incentives for
      attendance, and deterrents to absence.

PMID- 7630444
TI  - Dimensions of the staff nurse role in ambulatory care: Part III--Using research
      data to design new models of nursing care delivery.
AB  - A national survey of 606 practicing staff nurses provides the basis for a data
      set that delineates the desired future role for nurses in ambulatory care. The
      core dimensions of future practice can be used to develop new models of
      ambulatory nursing care delivery, such as primary prevention, primary health
      care, and primary nursing as well as a case management and paired-partners model.
      The final part in this series, which will be published in the September/October
      issue, will examine the development of nursing intensity measures, standards,
      clinical ladders, and quality improvement programs.

PMID- 7630445
TI  - Redesigning care delivery in the community hospital.
AB  - In 1991, Augusta Hospital Corporation implemented a patient care delivery
      redesign project in an effort to enhance overall quality of care while improving
      cost effectiveness. Preliminary findings suggest success in both of these
      endeavors.

PMID- 7630446
TI  - Nursing report cards--the nurse manager's challenge.

PMID- 7630448
TI  - Better APN practice measures needed.

PMID- 7630447
TI  - Lightening the load in the Federal suitcase.

PMID- 7630449
TI  - Collaborative relationships in the OR. Part I--Obstacles: the gatekeepers of
      privilege.

PMID- 7630450
TI  - The 21st century executive: new competencies for success.

PMID- 7630451
TI  - [Organic hyperinsulinism].

PMID- 7630452
TI  - [The Cochrane Collaboration and evidence-based medicine].

PMID- 7630453
TI  - [The Cochrane Collaboration; systematic reviews of knowledge from randomized
      studies].

PMID- 7630454
TI  - [Bibliometric indicators of the quality of medical scientific research in The
      Netherlands and Flanders].

PMID- 7630455
TI  - [What determines waiting time for cataract surgery, knee arthroscopy and total
      hip arthroplasty and how satisfied are the patients?].
AB  - OBJECTIVE: To gain an insight into the waiting periods for cataract, arthroscopic
      knee and total hip operations and the patients' opinion on this subject. DESIGN:
      Retrospective study. SETTING: The district of Groningen, the Netherlands. METHOD:
      A study population of 300 national health insurants who underwent a cataract
      operation (100), an arthroscopic knee operation (100) or a total hip operation
      (100) in 1992 and 50 private insurants who underwent a cataract operation in
      1992, was obtained by a select sampling. By a structured questionnaire,
      information about basic variables (age, gender, education, occupation, perceived
      urgency and form of insurance), waiting periods and opinions on the waiting
      periods was gathered. RESULTS: The waiting periods between the specialist
      consultation and the operation were 5.2 and 7 months for eye, knee and hip
      patients respectively. The waiting period per hospital varied from 4-7 months for
      an eye operation, 1-4 months for a knee operation and 2.5-12 months for a hip
      operation. The waiting period was not affected by basic variables, except the
      waiting period for hip operation which benefited from a high urgency declaration
      by the specialist. 60% of the eye patients, 45% of the knee patients and 47% of
      the hip patients were satisfied about the waiting period. 15% of all patients
      were dissatisfied about it. CONCLUSION: Waiting periods for operations in this
      study were not determined by patient-specific basic variables, varied strongly
      between hospitals and did not cause discontent among the majority of the
      patients, despite durations of mostly several months.

PMID- 7630456
TI  - [Mortality rate in lung cancer decreasing in men and increasing in women].
AB  - OBJECTIVE: To determine the trend in lung cancer mortality rates among men and
      women in the Netherlands during the period 1951 to 1992. DESIGN: Descriptive
      research. METHOD: In a previous paper the lung cancer mortality rates of men and
      women during the period 1951 to 1982 were analysed using the Netherlands Central
      Bureau of Statistics (CBS) population data and the CBS mortality data. The
      mortality rates were directly standardized for age using as a standard the Dutch
      sum population of 1951 to 1982. The current study describes the lung cancer
      mortality for men and women until 1992 using exactly the same methods. RESULTS:
      The direct standardized mortality rates for men had decreased since 1987. For
      women, on the contrary, these rates had increased further. The age-specific
      mortality rates for men have decreased since the calendar period 1983-1987 and
      since the birth cohort 1916-1920. The age-specific mortality rates for women have
      increased until the latest calendar period 1988-1992 and until the latest birth
      cohort 1931-1935. CONCLUSIONS: Lung cancer mortality in men has peaked, in women
      it is still rising.

PMID- 7630457
TI  - [Incidence and prevalence of hemoglobinopathies in children in The Netherlands].
AB  - OBJECTIVE: To evaluate the prevalence and incidence of thalassaemia major and
      sickle-cell disease in children. DESIGN: Descriptive nationwide epidemiological
      study. SETTING: Clinical Genetic Centre Utrecht. METHOD: Prevalence data were
      collected by a written survey among all 333 Dutch paediatricians (1992; response
      rate 99.1%). Incidence data are collected monthly by the Dutch Paediatric
      Surveillance Unit (1992/'93; response rate: 86%). RESULTS: In September 1992, 128
      children were being treated by a paediatrician for sickle-cell disease. Two
      children had parents born in the Netherlands, but all children were of other
      ethnic origins, mainly from Surinam, the Dutch Antilles, Turkey and Africa; 50
      children were born in the Netherlands. 31 children were under treatment for
      thalassaemia major, none of them of original Dutch descent; the most frequent
      ethnic backgrounds were Turkey and Morocco; 20 children were born in the
      Netherlands. From October 1992 till December 1993 (15 months) 18 children were
      newly diagnosed with sickle-cell disease, of whom 7 were born in the Netherlands,
      and 8 children were newly diagnosed with thalassaemia major, of whom 2 were born
      in the Netherlands. CONCLUSION: Sickle-cell disease and thalassaemia major are
      (still) rare diseases in the Netherlands. With the present migration and the
      increase of consanguineous marriage, they are expected to become a more important
      health issue.

PMID- 7630458
TI  - [Respiratory insufficiency due to pulmonary toxicity of amiodarone].
AB  - A 70-year-old woman suffering from atrial fibrillation was treated with
      amiodarone, but developed acute respiratory failure necessitating mechanical
      ventilation for four weeks. Pulmonary function remained restrictively impaired
      after weaning from the ventilation, due to pulmonary fibrosis. Pulmonary toxicity
      is a well-known adverse reaction to amiodarone, but it rarely requires mechanical
      ventilation. The Netherlands Centre for Monitoring of Adverse Reactions to Drugs
      received II reports of this life-threatening reaction since 1976.

PMID- 7630459
TI  - [Prevention of occlusion following peripheral bypass surgery using oral
      anticoagulants or acetylsalicylic acid: a randomized comparison within the Dutch
      BOA study].

PMID- 7630460
TI  - [Disciplinary jurisprudence of family physicians, 1982-1992].

PMID- 7630461
TI  - [Multiple and bilateral cerebral hydatid cysts. A case].
AB  - The authors report one case of multiple and bilateral cerebral hydatic cysts in a
      eight years old child. The disease was revealed by cranial hypertension signs,
      with homonymous hemianopsia. The diagnosis was based on the cerebral CT scan, and
      confirmed by surgical operation which was performed in two stages. The evolution
      was uneventful.

PMID- 7630462
TI  - [Paraganglioma of the cauda equina. Clinical aspects and MRI. Apropos of a case].
AB  - The clinical and imaging features of a paraganglioma of the cauda equina are
      presented. A peridural anesthesia revealed the cauda equina compression syndrome
      in a 68 years old man who presented first with a urinary retention. Total
      surgical excision of a long round-shaped encapsulated tumor was uneventful.
      Macroscopically this lesion filled up the spinal canal and resembled to a
      meningioma. It was firmly attached to the filum terminale. Adjacent large
      arterialized vessels visible on MRI were spared. Although the diagnosis could be
      evoked pre-operatively on some suggestive patterns on the MRI, the pathological
      findings finally confirmed the diagnosis of paraganglioma. Along with the
      evidence of specific light microscopic features, the use of an immunocytochemical
      demonstration of synaptophysine in these tumors allows a confident diagnosis to
      be made.

PMID- 7630463
TI  - [Unusual extra-axial infra-tentorial localization of a cavernoma in the cisterna
      magna].
AB  - A case of an extra-axial cavernous angioma of the cisterna magna is described.
      The clinical presentation, radiographic features, treatment of that unusual
      location in the posterior fossa are discussed. The patient is a 31 years old man
      admitted for the sudden onset of occipital headache and instability. A CT scan
      demonstrated a slightly calcified lesion, minimally enhanced after intravenous
      injection of a contrast agent, located within the posterior fossa. A T2-weighted
      MR image showed a well circumscribed mass, located between medulla oblongata and
      left cerebellar tonsil, of mixed signal intensity surrounded by a rim of
      decreased signal intensity related to the presence of hemosiderin. Cerebral
      arteriography was normal. A medial suboccipital craniectomy was performed, with
      the patient in the ventral position, in which a 1.5 x 1 cm solid dark-red mass
      was encountered arising from the cisterna magna and was easily removed "en bloc".
      The operative extra-axial aspect of that lesion was evident excluding a medulla
      oblongata tumor protruding into the cisterna magna. Histologically, the lesion
      was a cavernous angioma consisting of numerous vascular channels with collagen
      fibrous walls filled with fibrin thrombi and hemosiderin. Few elastic fibers were
      found in vascular walls. The patient's post-operative course was unremarkable.

PMID- 7630464
TI  - [Meningioma of the anterior part of the 3rd ventricle. Clinical case].
AB  - Although intraventricular meningiomas are rare, the location within the third
      ventricle is very uncommon. A case of a meningothelial meningioma of the anterior
      part of the third ventricle is presented. Clinical features disclose both signs
      of intracranial hypertension and signs related to the anterior third ventricle
      location. Using a transfrontal transventricular approach the tumor was totally
      removed and the follow up was uneventful. For determining the best operative
      approach, consideration of a number of principles is mandatory: 1. A precise
      angiographic study, a computerized tomography, magnetic resonance imaging with
      coronal and sagittal reconstructions to evaluate the lesion and the ventricles
      size; 2. Excessive retracted cerebral tissue must be avoid as like as to minimize
      incision in cerebral cortex, corpus callosum, lamina terminalis or fornicial
      raphe; 3. For a good excision of the lesion it is better to avoid excision "en
      bloc" with early coagulation of the feeding arteries.

PMID- 7630465
TI  - [Lymphocytic adenohypophysitis. Apropos of a new case].

PMID- 7630466
TI  - [Chronic spinal cord stimulation in the treatment of neurogenic pain. Cooperative
      and retrospective study on 20 years of follow-up].
AB  - The aim of this investigation is to evaluate the long-term spinal cord
      stimulation (SCS) efficacy and safety, with a 20-years study concerning 692
      patients (series I: 279, series II: 413). The series concern 304 arachno-epidural
      fibrosis, 152 peripheral nerve lesions, 25 amputations pain, 17 plexus brachial
      lesions, 101 spinal cord lesions, 22 cancer pain, and 71 vascular pain. A
      multidisciplinary chronic pain evaluation must exclude contra-indications
      (nociceptive pain, serious drug habituations, psychological problems, unresolved
      issues or secondary pain). Percutaneous epidural SCS is a screening method if the
      trial is sufficiently prolonged (3 to 14 days) and if the pain topography is
      overlapped by induced paresthesias. The immediate global results of the 2 series
      are similar: respectively 86% and 85% of success one month after implantation.
      With the same longterm follow-up (mean: 10 yrs, range: 2-20), and the same
      evaluation criteria, the percentage of long-term global success rate is 54% in
      series I, and 52% in series II. In the most recent period (1984-1990) concerning
      301 patients, the success rate are respectively 68% and 60%. Analysing the
      results etiologically confirms the therapeutic value of SCS for neurogenic pain
      secondary to partial deafferentation. For upper limb pain, ipsilateral radicular
      stimulation is preferable. When the nerve lesion extends to the pre-ganglionic
      portion (brachial plexus avulsion, herpes zoster) or in cases of pain of spinal
      or cerebral origin, thalamic stimulation must be considered, after failure of
      SCS.

PMID- 7630467
TI  - [Lumbar canal stenosis. Retrospective study of 158 operated cases].
AB  - The authors report the results of a retrospective study of 158 lumbar spinal
      stenosis (LSS), all operated (111 degenerative, 26 congenital, 21 mixed). Eighty
      seven percent of the patients had a low-back pain and 81.6% a radicular pain.
      Only 57.6% of them had a polyradicular claudication. A neurological deficit
      (motor, sensitive, or involving sphincters) was present in 36.6% of cases. A
      myelographic block was noted in 23.4% of cases, and in 20.3% a spondylolisthesis
      with an intact neural arch was found. Surgery consisted of a posterior lateral
      spinal canal calibration, sometimes associated with a ventral canal calibration
      (via the posterior route) (6.3%), and/or excision of a disc herniation at one
      (47.5%) or two levels (3.8%). Mean follow-up after surgery was 7.8 months. The
      global result was good or excellent in 75.2% of cases. Radicular pain was
      relieved in 89.1% of cases, and polyradicular claudication in 90.1% of cases.
      Neurological deficit improved in 50.6% of cases. In only 59.8% of cases relief of
      low-back pain was achieved. Statistically low-back pain (lasting for over 2
      years) improved less, but a preoperative spondylolisthesis didn't influence the
      quality of the result regarding this symptom. Semiology, pathophysiology, and
      surgery particularly regarding spine stability are discussed.

PMID- 7630468
TI  - [Lesions of the corpus callosum and syndromes of interhemispheric disconnection
      of traumatic origin].
AB  - We review the different kinds of injury to the corpus callosum in closed head
      trauma, as well as their different mechanisms. Most frequent lesions are either
      diffuse and at the microscopic level, secondary to disruption of axons at the
      time of the trauma, or focal and at macroscopic level, also due to torsion or
      shearing strains on the corpus callosum. They are associated with diffuse axonal
      injury of hemispheric and brainstem white matter. Focal macroscopic lesions,
      sometimes extensive, are encountered in 16-40% of autopsies after fatal head
      injury. Likewise, MRI allows nowadays to show them in 22-49% of nonfatal head
      injuries. Such lesions can produce an interhemispheric disconnection syndrome.
      However, clinical observation of an interhemispheric disconnection after head
      trauma has been only rarely reported in the literature, as it is showed by a
      brief overview of those cases, which suggests that this pathology is probably
      often overlooked. Focal damage to the corpus callosum seems to be a marker of
      severe injury, with often long-lasting coma and sometimes transitory vegetative
      state or mutism. Extension of posterior callosal lesions towards adjacent midline
      structures, such as the fornix, could contribute to the important memory
      impairment which is particularly frequently associated with posttraumatic
      interhemispheric disconnection syndromes.

PMID- 7630469
TI  - [Mechanisms of crystallization in the urine].

PMID- 7630470
TI  - [Renal response to exercise in healthy and diseased patients].
AB  - Exercise induces profound changes in the renal hemodynamics and protein
      excretion. Strenuous exercise provokes a major fall of the renal plasma flow and
      a reduction of the glomerular filtration rate. Despite these changes, the
      filtration fraction doubles at maximal exercise preserving the transfer of
      metabolites or substances through the glomerulus. A higher production of
      vasopressin and aldosterone enhances the tubular processes of water and
      electrolyte reabsorption, stabilising therefore the homeostasis during exercise.
      Urea, uric acid and lactate reabsorption are also increased. Postexercise
      proteinuria is directly related to the intensity of exercise rather than to its
      duration. This transient state may be explained by an increased glomerular
      membrane permeability and a partial inhibition of tubular reabsorption of plasma
      proteins. Postexercise proteinuria appears to be age-dependent. Exercise has an
      additional effect on protein excretion in patients with nephropathies (diabetes,
      renal diseases, kidney transplants).

PMID- 7630471
TI  - [*calcium-oxalate lithogenesis: crystallization in the presence of urine from
      healthy subjects].
AB  - In the present study we aim at describing the influence of urine of non-lithiasic
      subjects on the different crystallization stages of calcium oxalates. The
      experimental method consists in comparing the turbidimetric curves obtained by
      crystallization in pure synthetic urine to the curves obtained after addition of
      natural urine to the solution. Natural urine plays an important role on
      nucleation, crystal growth and agglomeration even if only small amounts (4% v/v)
      are added to the mother solution. Nucleation is favoured (decrease of the
      induction period and increase of the crystal number) by the presence of solid
      particles, such as cellular fragments, which play the role of substrates for
      heterogeneous nucleation. On the other hand, both the growth rate of the crystals
      and their degree of agglomeration are reduced. Moreover, the physical nature of
      the crystals which precipitate is different from that of the crystals which
      nucleate in synthetic urine. Under our conditions of high super-saturation,
      natural urine favours the nucleation of calcium oxalate dihydrate at the expenses
      of calcium oxalate trihydrate which forms in pure synthetic urine. A hypothesis
      on the origin of the lithogenesis process is made and a correlation between the
      localization of the calcium oxalate stones in the urinary tracts and their main
      constituents is proposed.

PMID- 7630472
TI  - [Adult uveitis: apropos of 1 case with acute idiopathic interstitial nephritis].
AB  - The association of acute interstitial nephritis and uveitis is rare. In 1975,
      Dobrin reported a new syndrome in two children presenting acute interstitial
      nephritis, anterior uveitis and marrow-lymph node granulomas. We report one case
      of this association in the adult. A 35-year-old man was admitted to the hospital
      for acute renal failure, arthralgia and anterior uveitis. The infectious and the
      immunological investigations were negative. The ocular examination shows
      bilateral anterior uveitis. The renal biopsy revealed acute tubulo-interstitial
      nephritis. He was treated by prednisone (0.5 mg/Kg/day). His clinical course was
      favorable. Seven years later, the renal function is normal and we not observed a
      relapse of his uveitis.

PMID- 7630473
TI  - [Hepatitis c virus infection and glomerulonephritis].

PMID- 7630474
TI  - [Phosphaturic effect of parathyroid hormone].

PMID- 7630475
TI  - [Importance of organic osmolytes in central pontine myelinolysis].

PMID- 7630476
TI  - [Polycystic kidney: complete structure of the PKD1 gene and its protein].

PMID- 7630477
TI  - [Gene therapy and antihypertensive treatment: effect of tissue kallikrein gene
      transfer].

PMID- 7630478
TI  - [A supplementary case of Amanita Proxima poisoning as the origin of acute renal
      insufficiency].

PMID- 7630479
TI  - GABAA/benzodiazepine receptor heterogeneity: neurophysiological implications.

PMID- 7630480
TI  - Comparison of the effects of sumatriptan and the NK1 antagonist CP-99,994 on
      plasma extravasation in Dura mater and c-fos mRNA expression in trigeminal
      nucleus caudalis of rats.
AB  - Dural plasma extravasation produced by electrical stimulation of the trigeminal
      ganglion was measured in rats and the concomitant expression of c-fos mRNA
      produced in the trigeminal nucleus caudalis (NtV) was measured using in situ
      hybridization techniques. The non-peptide NK1 receptor selective antagonist CP
      99,994 (1-3000 micrograms kg-1) and the 5HT1D receptor agonist sumatriptan (1
      1000 micrograms kg-1) reduced dural plasma extravasation dose-dependently with
      ID50S of 52 micrograms kg-1 and 30 micrograms kg-1 respectively. CP-99,994 (1000
      micrograms kg-1). a compound known to have good brain penetration, decreased c
      fos mRNA expression in the NtV by 37 +/- 7% without disruption of the blood brain
      barrier (BBB). Sumatriptan (1000 micrograms kg-1), known to be poorly brain
      penetrant, had no significant effect on c-fos mRNA expression in the NtV unless
      the BBB was disrupted by infusion of a hyperosmolar mannitol solution after which
      sumatriptan decreased c-fos mRNA expression by 65 +/- 11%. The results suggest
      that brain penetrant NK1 receptor antagonists may have anti-migraine effects
      peripherally through blockade of dural extravasation and centrally by inhibition
      of nociceptive pathways. Furthermore the data indicates that the anti-migraine
      action of sumatriptan must be predominantly peripherally mediated, be it via
      inhibition of plasma extravasation or direct vasoconstriction, since it had
      little effect on the activation of neurones in the NtV unless the BBB was
      disrupted.

PMID- 7630481
TI  - 5-Hydroxytryptamine3 receptor antagonism modulates a noxious visceral
      pseudoaffective reflex.
AB  - 5-Hydroxytryptamine (5-HT) receptor agonists and antagonists were dosed
      intravenously (i.v.) and studied for their effects on the depressor
      cardiovascular pseudoaffective reflex evoked by acute noxious colo-rectal
      distension in the anaesthetized rat. Methiothepin (100 micrograms kg-1) caused an
      initial, unsustained blockade of evoked depressor responses whilst ketanserin
      (100 micrograms kg-1) was without effect. By comparison, ondansetron dose
      dependently inhibited evoked depressor responses and was maximally active at 100
      micrograms kg-1, causing a 57.5 +/- 0.9% reduction. An ID50 value of 36.7
      micrograms kg-1 was estimated by regression analysis. In contrast, granisetron
      caused complete blockade of the depressor response with an ID50 of 0.4 microgram
      kg-1. Bell-shaped dose-effect curves were demonstrated for both granisetron and
      ondansetron. Intrathecal dosing with granisetron (100 ng) into the thoracolumbar
      region of the spinal cord prevented the depressor response to colo-rectal
      distension, suggesting a spinal site of action. The pseudoaffective depressor
      responses were not facilitated by pre-dosing with the 5-HT receptor agonists, 8
      OH DPAT, alpha-methyltryptamine or 1-phenyl-biguanide. However, 8-OH DPAT (100
      micrograms kg-1) facilitated pressor responses. It is suggested that 5-HT3-like
      receptors may have a role in modulating depressor responses to visceral pain and
      that in this action different 5-HT3 receptor antagonists are not necessarily equi
      effective.

PMID- 7630482
TI  - DTG-induced circling behaviour in rats may involve the interaction between sigma
      sites and nigro-striatal dopaminergic pathways.
AB  - The distribution of sigma sites in brain areas enriched in dopamine, and the
      finding that circling behaviour can be elicited by specific sigma ligands such as
      DTG (di-o-tolylguanidine) suggest a modulatory role of these sites in the
      dopaminergic system. The present study was carried out to investigate further
      this hypothesis. Circling behaviour induced in rats by unilateral intranigral
      injection of DTG (10 nmol/rat) was decreased by haloperidol (0.1 mg/kg, i.p.),
      clebopride (0.25 mg/kg, i.p.) and SCH 23390 (0.03 mg/kg, s.c.) indicating that an
      interaction between sigma sites and the midbrain dopaminergic system may be
      involved in this rotational behaviour. Microdialysis experiments in freely moving
      rats showed that unilateral intranigral injection of DTG (5, 10, 20 nmol/rat)
      produced increases in extracellular levels of dopamine metabolites (DOPAC, HVA)
      in the ipsilateral striatum which correlated with the number of rotations. In
      addition intranigral injection of DTG (10 nmol/rat) produced increases in
      tissular dopamine metabolite levels in the ipsilateral striatum without affecting
      dopamine metabolite levels in limbic structures. These results indicate that
      sigma sites may be involved in the modulation of the dopaminergic motor system.

PMID- 7630483
TI  - Cellular defence mechanisms in the striatum of young and aged rats subchronically
      exposed to manganese.
AB  - A deficiency of striatal dopamine (DA) is generally accepted as an expression of
      manganese (Mn) toxicity in experimental animals. Since compromised cellular
      defence mechanisms may be involved in Mn neurotoxicity, we investigated the
      response of the neuronal antioxidant system [ascorbic acid (AA) oxidation,
      glutathione (GSH) and uric acid levels] and neurochemical changes in the striatum
      in aged rats exposed to Mn. Levels of dopamine (DA), dihydroxyphenylacetic acid
      (DOPAC), homovanillic acid (HVA), 5-hydroxytryptamine (5-HT), 5
      hydroxyindoleacetic acid (5-HIAA), AA, dehydroascorbic acid (DHAA), GSH and uric
      acid were determined after subchronic oral exposure to MnCl2 200 mg/kg (3-month
      old rats) and 30-100-200 mg/kg (20-month-old-rats). Aged rats had basal levels of
      striatal DA, DOPAC, HVA, 5-HT, 5-HIAA, GSH and AA lower than those of young rats.
      In the striatum of aged rats, Mn induced biphasic changes in the levels of DA,
      DOPAC, HVA (an increase at the lower dose and a decrease at the higher dose) and
      DHAA (opposite changes). Mn decreased GSH levels and increased uric acid levels
      both in the striatum and in synaptosomes in all groups of aged rats. All of these
      parameters were affected to a lesser extent in young rats. In conclusion, the
      response of cellular defence mechanisms in aged rats is consistent with a Mn
      induced increase in the formation of reactive oxygen species. An age-related
      impairment of the neuronal antioxidant system may play an enabling role in Mn
      neurotoxicity.

PMID- 7630484
TI  - 3,4-Diaminopyridine induced hydrolysis of phosphoinositide in cultured neurons
      from embryo chick forebrain.
AB  - The effect of 3,4-diaminopyridine (DAP) on phosphoinositide hydrolysis in
      cultured neurons from embryo chick forebrain has been studied. DAP produced a
      dose- and time-dependent accumulation of inositol phosphates. At 1 mM DAP a
      maximal effect was obtained. In Ca2+ free medium, DAP-activated turnover of
      phosphoinositide was reduced, but was still significant. Blocking Ca2+ entry with
      200 microM Cd2+ also did not abolish the DAP-induced accumulation of inositol
      phosphates. As a comparison the effect of high K+ exposure was investigated. High
      K+ enhanced phosphoinositide hydrolysis, and this effect was also reduced by
      excluding Ca2+ influx. Moreover, DAP had no additional effect on the high K(+)
      induced hydrolysis of phosphoinositide. Using oxonol-V, a depolarization of the
      membrane potential was seen in the neurons bathed in DAP containing medium. It is
      suggested that the depolarization may play a role in DAP-activated
      phosphoinositide turnover in cultured neurons of the embryo chick forebrain, but
      that Ca2+ entry is not necessary for this effect.

PMID- 7630485
TI  - Opioidergic inhibition of capsaicin-evoked release of glutamate from rat spinal
      dorsal horn slices.
AB  - We investigated the effects of opioid agonists on the capsaicin-evoked release of
      glutamate from nociceptive primary afferent fibers of the rat (6-8 weeks) using a
      fluorometric on-line continuous monitoring system for glutamate. In the presence
      of 0.3 microM tetrodotoxin, the application of 3 microM capsaicin to spinal
      dorsal horn slices produced an evoked glutamate release (55.9 +/- 4.02 pmol.mg-1
      protein, n = 15). DAMGO ([D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin; 0.3-10 microM) and
      morphine (1-30 microM), mu-opioid agonists, produced a concentration-dependent
      reduction (approximately 85 and approximately 77% reduction, respectively) in the
      capsaicin (3 microM)-evoked release of glutamate. These inhibitory effects were
      significantly antagonized by naloxone (1 microM). DPDPE ([D-Pen2,5]enkephalin; 1
      10 microM), a delta-opioid agonist, also reduced the capsaicin-evoked release in
      a concentration-dependent manner (approximately 59% reduction). Naltrindole (1
      microM), a selective delta-antagonist, significantly antagonized the inhibitory
      effect of DPDPE (10 microM). In contrast, neither U-50,488H (1-10 microM) nor U
      69,593 (10 microM), kappa-opioid agonists, had any effects on the evoked release
      of glutamate. These results suggest that mu-, and delta-opioid agonists modulate
      pain transmission in the spinal dorsal horn, at least in part, by inhibiting the
      release of glutamate from capsaicin-sensitive primary afferents.

PMID- 7630486
TI  - Effects of muscarinic receptor stimulation of sympathetic preganglionic neurones
      of neonatal rat spinal cord in vitro.
AB  - Whole cell current-clamp recordings were made from 85 sympathetic preganglionic
      neurones (SPN) of the neonatal spinal cord in vitro. Superfusion of up to 500
      microM acetylcholine (2-30 sec) gave weak responses. Carbachol (CChol; 5-50
      microM) superfused for 1-20 sec, hyperpolarized SPN. This response was associated
      with a mean reduction in input resistance of 22%. Ion substitution studies
      suggested that potassium is the likely carrier of at least part of the current
      underlying the CChol-induced hyperpolarization. Some SPN display spontaneous
      rhythmic oscillations in their membrane potentials which may be due to action
      potential discharge in electrically-coupled neurones. CChol also acts to inhibit
      these oscillations concomitant with the hyperpolarization. Responses to CChol
      were unaffected by addition of 500 nM TTX to the bathing medium suggesting that
      CChol acts directly upon SPN. Carbachol-induced hyperpolarizing responses were
      totally abolished by the non-specific muscarinic receptor antagonist atropine (20
      50 microM). Pirenzepine, at concentrations over 5 microM reversibly reduced the
      responses to CChol. Gallamine, an M2 receptor antagonist applied at 25 microM
      also reversibly abolished the CChol responses. These results suggest that CChol
      mediated hyperpolarizations may be due to M2 receptor activation.

PMID- 7630487
TI  - Inhibition of N-type Ca2+ channel currents in human neuroblastoma (SH-SY5Y) cells
      by muscarine via stimulation of M3 receptors.
AB  - The effects of muscarine on whole-cell Ca2+ channel currents in SH-SY5Y cells
      were studied using conventional and perforated-patch-clamp techniques, with 10 mM
      Ba2+ as charge carrier. Muscarine (10-300 microM) caused concentration-dependent
      inhibitions of Ca2+ channel currents which were only reversible when perforated
      patch recordings were used. Inhibition of currents was associated with slowing of
      activation kinetics in approximately 50% of cells. In the presence of 5 microM
      nifedipine, muscarine was still able to inhibit currents, but after pre-exposure
      of cells to 1 microM omega-conotoxin GVIA the inhibitory effects of muscarine
      were almost completely lost. In the presence of 100 microM muscarine, Bay K 8644
      (5 microM) was still able to enhance current amplitudes. Pre-treatment of cells
      with pertussis toxin (250 ng/ml for 16-24 hr) or inclusion of 1 mM GDP-beta-S in
      the patch-pipette prevented the inhibitory actions of muscarine.
      Hexahydrosiladifenidol (0.1-1 microM) antagonized the actions of muscarine
      (calculated pA2 7.1) but the presence of 10 microM pirenzipine or 0.1 microM
      methoctramine in the bath solution did not alter the degree of current inhibition
      caused by 100 microM muscarine. In summary, these results indicate that muscarine
      in SH-SY5Y cells causes inhibition of N-type Ca2+ channels via a M3 receptor
      coupled to a pertussis toxin-sensitive G-protein.

PMID- 7630488
TI  - Ethanol sensitivity of heteromeric NMDA receptors: effects of subunit assembly,
      glycine and NMDAR1 Mg(2+)-insensitive mutants.
AB  - In the current study, dimeric and trimeric combinations of N-methyl-D-aspartate
      (NMDA) receptor subunits were expressed in Xenopus oocytes and their sensitivity
      to ethanol was examined using conventional two electrode voltage clamp methods.
      In oocytes expressing the NR1/2A subunits, ethanol (25, 50 and 100 mM) inhibited
      NMDA (100 microM)/glycine (10 microM) induced currents by 21, 31 and 47%;
      respectively. NMDA-stimulated currents in oocytes expressing NR1/2B currents were
      inhibited by 13, 25 and 45% while NR1/NR2C currents were inhibited by 6, 11 and
      24%. Ethanol inhibition of NMDA-stimulated currents in oocytes injected with
      NR1/2A/2B or NR1/2A/2C was not significantly different from that observed in
      NR1/2B or NR1/2C injected oocytes, respectively. With all receptor combinations,
      ethanol inhibition was rapid, reversible and not altered by pre-incubation. In
      the absence of ethanol, glycine enhanced NMDA-induced currents with an EC50 of
      1.42 microM for the NR1/NR2A combination and 0.51 microM for the NR1/NR2C
      combination. Ethanol inhibited NMDA-induced currents at all glycine
      concentrations tested (1-100-microM) and did not significantly alter the EC50
      value for glycine suggesting that ethanol does not compete for the glycine site
      on the NMDA receptor. Finally, three NR1 mutants which have been previously shown
      by others to possess either decreased Mg2+ sensitivity and Ca2+ permeability
      (N616Q and N616R) or reduced current amplitude (F609L) were tested for their
      ethanol sensitivity when expressed in combination with the NR2A subunit.
      Substitution of the wild-type NR1 with F609L did not alter the sensitivity of the
      receptor to ethanol.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7630489
TI  - Neurophysiological investigations of the features of the state and physiological
      activity of some structures of the striopallidum and thalamus in various forms of
      parkinsonism.
AB  - The results of many years of investigations of the features of the functional
      state and physiological activity of some structures of the striopallidum (Cd, GP,
      Put) and thalamus (VP, VL, CM) as links in the brain systems of the organization
      of mental and motor activity in patients with various forms of parkinsonism are
      presented in generalized form. The possibilities for the use of various types of
      ultraslow physiological processes to study the brain mechanisms of the
      activational and emotional states, with more precise definition of the role of
      structures of the striopallidal complex in the formation of systems supporting
      these types of mental activity in parkinsonism, are reviewed.

PMID- 7630490
TI  - Characteristics of the influences of the centrum medianum of the thalamus on the
      neuronal activity of the caudate nucleus.
AB  - The specific character of the relationship of the baseline cellular activity of
      the caudate nucleus to the features of the impulse activity of the centrum
      medianum of the thalamus has been identified in chronic microelectrode
      experiments. Reciprocal changes in the bioelectrical activity were recorded in
      the first group of cells, with a low action potential repetition frequency, while
      unidirectional changes with reorganizations in the intralaminar nucleus were
      recorded in the second. The activation of the cells of the centrum medianum of
      the thalamus was accompanied during the formation of an instrumental conditioned
      defense reflex by the formation of a pattern of impulse activity in neurons of
      the neostriatum which coincided in sign with the reorganizations which were
      characteristic during the investigation of the baseline activity. It is
      hypothesized that the features of the internal structure of the caudate nucleus
      underlie such a relationship.

PMID- 7630492
TI  - Reversible blockade, induced by the neurotoxin MPTP, of corticofugal impulse
      activity to neurons of the caudate nucleus in cats.
AB  - It has been demonstrated in acute experiments in cats anesthetized with nembutal
      and immobilized with ditilin [succinylcholine iodide--Translator] that the number
      of neurons of the caudate nucleus responding to a single stimulation of the motor
      cortex with action potentials with a latent period less than 8.0 msec in the
      first 10-12 days after a course of injections of MPTP (5 mg/kg daily for 5 days,
      intramuscularly) decreased significantly as compared with the control. Their
      number is gradually restored by the 45th-54th day after the administration of the
      neurotoxin. A one-time injection of the dopaminomimetic, apomorphine (5 mg/kg,
      intramuscularly), also significantly decreases the number of neurons with a
      latent period of the responses less than 8.0 msec for 5 h in the intact animals,
      and is incapable of removing the blockade of the corticoneostriatal impulse
      activity in animals with an MPTP-induced dopamine deficit. The hypothesis is
      advanced that dopamine exerts a protective inhibitory influence on the conduction
      of corticofugal glutamatergic impulse activity to neurons of the neostriatum.

PMID- 7630491
TI  - Neurochemical characteristics of the rat neostriatum and motor cortex after the
      development of a unilateral manipulatory reflex.
AB  - Indicators of the activity of acetylcholinesterase (ACE), 5'-nucleotidase (NT),
      adenylate cyclase (AC) in the sensorimotor cortex and the neostriatum (NS) of the
      right and left cerebral hemispheres of control rats and rats trained to perform a
      food-procuring movement by pressing against an obstacle with the forelimb. An
      identical level of the averaged bilateral values of the activity of NT and AC in
      both of the structures in question and an increased ACE activity in the NS were
      found in the control animals. After the development of a manipulatory skill, the
      activity of AC decreased in the cortex and the NS in the presence of unchanged
      ACE activity, while NT activity decreased in the cortex and increased in the NS.
      The bilateral values of the activity of the enzymes differed significantly in
      well and poorly trained rats. At the same time, the activity of the enzymes was
      similar in character in the dominant and subdominant hemispheres for each group
      of animals. Overall the neurochemical changes obtained can be regarded as
      specific correlates of the developed unilateral manipulatory reactions that are
      characteristic for the structures in question of both cerebral hemispheres.

PMID- 7630493
TI  - Striohypothalamic functional connections in pharmacologically induced catalepsy
      in Wistar rats.

PMID- 7630494
TI  - Participation of the cholinergic system of the dorsal and ventral striatum in the
      regulation of various forms of defense behavior.

PMID- 7630495
TI  - Analysis of the caudatoventrotegmental influences during the realization of the
      motor alimentary conditioned reflexes.

PMID- 7630496
TI  - Quantitative ultrastructural characteristics of GABAergic synaptic terminals on
      neurons of the reticular portion of the substantia nigra.

PMID- 7630497
TI  - Interdependance of the level of the steady potential of the brain and visual
      evoked potentials in human aging: the norm and Alzheimer's disease.
AB  - The interrelationships between the amplitude-temporal parameters of the visual
      evoked potential (VEP) and of the level of the steady potential (LSP) of the
      brain in healthy middle-aged and elderly people and in Alzheimer's disease
      patients. The existence of a statistically significant correlation between the
      LSP and the amplitude-temporal characteristics of the VEP. The interrelationship
      is intensified both during aging in the norm and especially in Alzheimer's
      disease patients. The most stable positive correlation exists between the local
      LSP and in the occipital region and the amplitudes of the N1 and P2 components of
      the VEP.

PMID- 7630499
TI  - Study by nontraditional analytic methods of features of cortical potentials,
      taking high-frequency components into account, in dogs during instrumental
      learning.
AB  - A new method has been developed for the coding of EEG tracings which is an
      alternative to the classical spectral correlation analysis. This method has made
      it possible to compensate to a considerable degree for limitations which are
      unavoidable with the Fourier transform, and to obtain additional information
      regarding the form of the tracing, which reflects the fluctuations of brain
      potentials. The new system that has been presented for coding the EEG is, in our
      view, the most adequate (of the methods known to us) for identifying the
      individual features of the EEG, in terms of evaluating both their regional
      differences and similarities. The data obtained convince us once again of the
      real existence of high-frequency low-power components of the EEG, and their
      enhancement during instrumental learning in dogs (motor alimentary conditioned
      reflexes). In addition, data have been obtained pointing to the intensification
      in some regions of a slow-wave constituent; this has not been observed previously
      in carrying out a Fourier transform.

PMID- 7630498
TI  - Electroencephalographic correlates of neurological disturbances at remote periods
      of the effect of ionizing radiation (sequelae of the Chernobyl' NPP accident).
AB  - The psychoneurological status of 40 participants (all men aged 25-45 years,
      official dose 15-51 rem) in the liquidation of the consequences of the accident
      at the Chernobyl Nuclear Power Plant in 1986-1987 was investigated; EEG mapping
      and three-dimensional localization of the sources of epileptic activity as
      compared with the data of healthy individuals (20 individuals) was carried out.
      Vegetative-vascular symptomatology was identified in the neurological status of
      all the patients; disseminated organic neurological symptomatology and endocrine
      disturbances were additionally identified in some of the patients. There were
      paroxysmal attacks periodically in the overwhelming majority (68%) of the
      patients; this correlated with the presence in the EEG of epileptic forms of
      activity. The patients were divided into two groups on the basis of the character
      of the EEG. Patients in whom slow alpha waves and waves of the theta range with a
      "focus" in the central-frontal regions of the cortex were recorded were included
      in group I (25 individuals). Analysis of the localization of the sources of
      epileptic activity revealed placement at the midline level in them with marked
      compactness and displacement of the focus to the right hemisphere. In the
      patients of group II (15 individuals), slow waves of frontal localization and
      diffuse beta waves predominated in the EEG in the presence of a reduction in the
      level of biopotentials. The localization of equivalents of epileptic activity was
      more diffuse in character and was at the basal level, with a greater
      representation of the sources of epileptic activity in the left
      hemisphere.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7630501
TI  - Significance of the interstimulus time interval in repeating combined
      presentations of L-glutamate and acetylcholine for change in the reactivity of
      cortical neurons.
AB  - A comparative study of the probability, directionally, and intensity of the
      changes in the baseline and L-glutamate (Gl)- and acetylcholine(ACh)-induced
      average frequency of the impulse activity (BIA, GlIA, and AChIA, respectively) of
      individual neurons of the sensorimotor cortex of unanesthetized rats in the
      course of repeated isolated and combined presentations of Gl and ACh showed that
      the process of reduction in reactivity to Gl is slowed in the population of cells
      which experienced the combined action of Gl and ACh with a 1.5 second
      postponement of applications of ACh in comparison with the situation of its
      isolated and combined presentation with a 3 second postponement of ACh. The AChIA
      decreases to a greater degree in the case of a 3 second postponement of ACh, and
      the probability of an increase in BIA is less than with the isolated application
      of ACh. It is concluded that the character of the dynamics of the reactivity of
      neurons is determine by the temporal relationships of local neurochemical
      stimuli.

PMID- 7630500
TI  - Monoaminergic control by amygdalar nuclei of the reinforcing action of
      conditional stimuli.
AB  - The influence of microinfusion of 5-HT, NE, and DA into the amygdalar nuclei on
      the accomplishment of conditioned reinforcing and conditioned trigger reflexes
      which are constituents of the CADR was studied in cats with a developed
      conditioned alimentary discrimination reflex (CADR) in response to two
      conditional light stimuli set apart on different sides of a box. It was
      established that 5-HT in doses of 30-50 micrograms in a volume of 5 microliters
      elicits inhibition; the same doses of NE, by contrast, induces the "hanging-up"
      of the animals on conditional and conditional--unconditional stimuli which
      possess the property of reinforcement during the execution of the CADR. The
      microinfusion of DA in doses of 30-60 micrograms recalls, from animal to animal,
      the action of 5-HT and NE. It is hypothesized that the inhibitory functions of 5
      HT and the activating actions of NE in the amygdalar nuclei support this
      structure's control of reinforcing conditional and conditional--unconditional
      reflexes and the perception of the reinforcing action of conditional stimuli. It
      is hypothesized that the DAergic innervation of the amygdala does not participate
      directly in conditioned reflex activity.

PMID- 7630502
TI  - Behavior of rats during chronic activation and blockade of the neostriatal opiate
      system.
AB  - The effects of daily microinjections (MI), over of three weeks, bilaterally into
      the rostral striatum, of morphine, promedol, native leu-enkephalin and its
      synthetic tetrapeptide analogs were studied in experiments on rats. Naloxone was
      used as an antagonist. An active avoidance conditioned reflex was developed
      preliminary in a shuttle box. A decrease in the accuracy of the realization and
      an increase in the latent period of the reflex were observed after the first MI
      of morphine and enkephalins. The effect of the most stable aminated ornithine
      containing tetrapeptides proved to be the strongest. A search stereotypy and
      increased motoric activity were recorded in the rats during the development of
      the chronic effects of the activators of the opiate system. A clear correlation
      was not found between the motor and conditioned reflex shifts. The blockade of
      the opiate receptors with naloxone did not lead to substantial changes in
      behavior. The data obtained confirm the current hypothesis regarding the
      important role of the enkephalinergic system of the neostriatum in the regulation
      of complex forms of behavior and its close functional association with the
      dopaminergic system.

PMID- 7630504
TI  - Influence of female sex steroids on the capacity of splenocytes to form an
      adoptive immune response. Role of prostaglandin F2a in the mechanisms of hormonal
      immunoregulation.

PMID- 7630503
TI  - Participation of cardioactive peptides in habituation and sensitization of the
      synaptic input of command neurons of snail defense behavior.
AB  - The influence of serotonin, a small cardioactive peptide (SCPb) and FMRFamide on
      the time course of the responses of defense behavior command neurons in response
      to rhythmic stimulation of the intestinal nerve was studied in a preparation of
      the isolated common snail nervous system. It was found that the application of
      serotonin and SCPb induces an increase in the absolute magnitude of the synaptic
      response of the neurons under investigation; however, testing of the time course
      of the responses against the background of the action of these substances reveals
      the absence of sensitization and an increase in the rate of habituation to the
      rhythmic stimulus. The effect of the action of FMRFamide was entirely opposite to
      the effect of serotonin and SCPb, in both the influence on the amplitude of the
      single response and on the rate of habituation of the responses of the neurons.
      The data obtained point to the independence of the subcellular mechanisms of
      sensitization and habituation.

PMID- 7630505
TI  - Magnetic stimulation in the diagnosis of diseases of central and peripheral
      nervous system.

PMID- 7630506
TI  - Receptor binding of glutamate in the striatum of rats differing in learning
      capacity.
AB  - A comparative investigation has been carried out for the first time of the
      receptor binding of glutamate with synaptic membranes and coarse fractions of the
      postsynaptic enlargements isolated from the striatum of rats differing in their
      capacity to develop an alimentary instrumental reflex. It was demonstrated that
      the number of that glutamate binding sites on the postsynaptic enlargements
      isolated from the striatum of rats capable of rapidly developing an alimentary
      instrumental reflex was increased as compared with animals not subjected to
      training. This relationship is maintained two months after the termination of
      training.

PMID- 7630507
TI  - [Estrogens and bone metabolism].
AB  - The authors present a review referring to cellular and biochemical control
      systems of bone remodeling as well as the effect of estrogens on modulation of
      bone metabolism. Systemic and local control factors such as PTH, calcitonin,
      vitamin D, prostaglandins, insulin-like growth factor-1, transforming growth
      factor-beta are analyzed as possible indirect targets for the estrogen induced
      inhibition of bone resorption. A direct receptor-linked action of estrogens on
      the osteoblast-lining cell unit, the most important modulator or bone metabolism,
      is furtherwise examined. The precise mechanism of the beneficial effect of
      estrogens for the prevention of postmenopausal bone loss and the treatment of
      established osteoporosis has not yet been clearly identified, but it seems likely
      that multiple mechanisms may be involved since postmenopausal osteoporosis itself
      appears as a heterogenic clinical condition related to multiple pathogenetic
      factors.

PMID- 7630508
TI  - [The Pap-test in the study of viral infections of the female genital tract].
AB  - The authors underline a synergism of HPV + HSV and HPV + CIN that, together with
      general immunodeficiency and local factors are responsible for the oncogenesis of
      cervico carcinoma. This thesis takes on importance after literature reports of an
      increase of 10% in viral infections from HSV and HPV with a middle incidence of
      the 1-2% in all the colpocytologic examination cases not in women between 18 and
      65 years. To obtain a successful preventive treatment the authors recommend a
      colpocytologic examination each year, possibly in association with colposcopic,
      histologic and molecular studies in all HPV positive cases.

PMID- 7630509
TI  - [Isolated splenic metastasis of ovarian endometrioid carcinoma. A clinical case].
AB  - The authors describe a case of solitary spleen metastasis of an endometrioid
      ovarian cancer exceptionally reported in the literature. The follow-up of the
      patient is 12 months without recurrence.

PMID- 7630510
TI  - [Radiosurgical excision in the treatment of cervical intraepithelial neoplasia].
AB  - 39 patients affected by CIN had undergone radio surgical excision. This non
      traumatic method employs 3.8 MHz radio waves are employed to cut and/or
      coagulate. The radio surgical excision was carried out by a loop electrode, or
      microneedle, according to the colposcopic, histologic and microcolpohysteroscopic
      characteristics of the cervical lesion. In fact 14 patients, among whom 11
      affected by CIN I and 4 by CIN II with a total visibility of squamous columnar
      junction and not extended lesion of the cervical canal, had undergone radio
      surgical excision through various dimensions loop according to the size of the
      tissue to be excised. Whereas 10 CIN II patients who had not entirely visible
      squamous columnar junction or large cervical canal lesion, and 14 CIN III
      patients underwent to radiosurgical conization through a subtle and extensible
      tungsten thread according to the size of the tissue to be excised. In the 100% of
      the both groups the recovery was confirmed after three and six months. Inno cases
      cervical canal stenosis was observed and the squamous columnar junction resulted
      well visible. In both groups no thermal damages on the excised tissue, which
      could create difficulties on the histological diagnosis, were observed.
      Therefore, this method resulted an easy and cheap technique to be executed in
      surgery with excellent results under the therapeutic and economical aspect.

PMID- 7630512
TI  - [Blood groups of the ABO system and survival rate in gynecologic tumors].
AB  - A retrospective analysis of 968 women affected by gynecological tumors was
      conducted to assess the existence of a difference in survival between patients
      with different blood groups. Data are presented on 237 cases of endometrial
      cancer, 92 cases of ovarian cancer and 639 cases of invasive cervix cancer,
      detailing their ABO blood antigenic phenotypes, the stage of neoplasia and the
      treatment received. With regard to endometrial cancer, a sensibly better 5-year
      and 10-year survival is associated with blood group 0 if compared with blood
      group A. This finding is more evident when 5-year survival is considered among
      patients affected by ovarian cancer. With regard to cervical cancer, analysis
      showed that a little better than 5-year survival is associated with 0 blood
      phenotype; on the contrary, when a 10-year or longer survival is considered, a
      better survival is associated with A blood phenotype. The present study confirms
      evidence of an association between the A blood group and gynecological tumors.
      Endometrial and ovarian cancer occur more frequently in women with blood type A
      than in those with the other blood types, moreover, in the same tumors blood
      group A is associated with a poor prognosis. The possible reason for these
      findings are discussed with detailed regard to the possible biological importance
      that, at present, is conferred to the ABO group system in the complex activities
      of the immune system.

PMID- 7630511
TI  - [Diagnostic accuracy in transvaginal echography in benign endometrial diseases
      and its comparison with hysteroscopic biopsy].
AB  - Abnormal uterine bleeding is one of the main indications for hysteroscopy in peri
      menopausal age. Transvaginal ultrasound allows for an accurate study of the
      endometrium through the evaluation of thickness, homogeneity. The aim of this
      retrospective study was the evaluation of transvaginal ultrasound versus
      hysteroscopy in diagnostic approach to abnormal uterine bleeding in peri- and
      post-menopause. 130 Women referred to the Department of Obstetrics and Gynecology
      of the University of Pavia for abnormal uterine bleeding entered the study; all
      them underwent transvaginal ultrasound and hysteroscopy with directed biopsy,
      with histological diagnosis of benign endometrial disease. On the basis of
      endometrial thickness measured at ultrasound, premenopausal patients were divided
      into two groups, post menopausal patients into three groups, and for each group a
      comparison between hysteroscopic findings, histological diagnosis and echographic
      aspect was performed. A 100% correspondence between ultrasound, hysteroscopy and
      histology was found in the group of subjects with endometrial atrophy, with an
      endometrial thickness of 2.9 +/- 0.68 at ultrasound; in the remaining groups
      sensibility and specificity of transvaginal ultrasound seem to be lower. In our
      experience a cut-off of 4 mm can be established for endometrial thickness
      measured by transvaginal ultrasound. Values that are below this cut-off point are
      diagnostic for endometrial atrophy, precluding the need for more invasive
      examinations: a medical treatment can then be administered. On the contrary, an
      endometrial thickening of 4 mm or more requires an hysteroscopic examination with
      directed biopsy and histological diagnosis.

PMID- 7630513
TI  - [Fetal macrosomia and mode of delivery].
AB  - During the period 1988-1993 the route of delivery in 482 infants with birth
      weight > or = 4000 grams was studied. Normal vaginal delivery occurred in 396
      (82.1%) cases, vacuum extractor in 8 (1.6%) cases and caesarean section in 78
      (16.1) cases. Elective induction of labor with oxytocin and/or amniotomy was
      carried out in 25 cases of macrosomia. Perinatal death and shoulder dystocia
      never occurred in these macrosomic babies, but clavicles abruption (27 cases),
      cephalohaematoma (2 cases), shoulder-bladehaematoma (1 case) and birth brachial
      palsy (1 case) were observed. Because, in our experience, elective induction of
      labor increased the operative delivery rate (caesarean section, vacuum
      extractor), we conclude that mothers with macrosomic fetuses can safely be
      managed expectantly unless there is a indication for induction or caesarean
      section.

PMID- 7630514
TI  - [Constipation following hysterectomy. Retrospective study based on 105 cases].
AB  - Constipation after surgery is considered as a subgroup of patients in whom the
      disorder begins after pelvic surgery. A group of patients (median age 52 years
      with a range of 34-65 years) who had a hysterectomy underwent a retrospective
      study with the aid of a questionnaire and clinical records, to evaluate the
      incidence of constipation before and after the operation. Forty patients were
      operated on for benign pathology and 65 for malignant pathology. Forty-two
      patients underwent a Wertheim-Meigs, 39 had laparohysterectomy, 20 had a
      colpohysterectomy and 4 had a Schauta. The incidence of constipation increased
      from 25% preoperatively to 38% postoperatively (p < 0.05). There is no difference
      in the incidence of postoperative constipation among the various operations.
      Constipation after hysterectomy is associated with urinary disorders. These data
      confirm previous studies on the effect of hysterectomy on urinary and defaecatory
      functions and they show how a simple colpohisterectomy can cause constipation.

PMID- 7630515
TI  - [Outcome of drug-induced pregnancies].
AB  - The authors analysed 153 pregnancies achieved after different drug treatment to
      induce ovulation. The outcome of single and multiple pregnancies, the fetal
      malformation and male/female ratio were considered. The results obtained show
      that induction of ovulation seem to raise the risk of miscarriage when compared
      with outcome of spontaneous pregnancies; the malformation risk is not
      considerable.

PMID- 7630516
TI  - [Bromocryptin + gonadotropin vs. goserelin + gonadotropin in ovulation induction
      in patients with polycystic ovaries].
AB  - OBJECTIVE: To evaluate the efficacy and tolerability of treatment with goserelin
      + HMG vs bromocriptine + FSH + HMG in the induction of ovulation in patients with
      ovarian polycystosis. EXPERIMENTAL DESIGN: A randomized prospective study.
      PATIENTS: Sterile women with ovarian polycystosis of the first type not
      responding to clomiphene citrate. TREATMENT: Group A: bomocriptine + FSH + HMG
      (10 patients); Group B: goserelin depot (Zoladex) + HMG (18 patients). RESULTS: A
      greater percentage of ovulations, pregnancies and a higher success rate were
      obtained in Group B. The percentage of hyperstimulation was similar in both
      groups; there was a higher percentage of abortion in Group A. Cycle duration and
      the number of phials of gonadotropin were greater in Group B. CONCLUSIONS:
      Treatment with bromocriptine + gonadotropin remains the simplest; the treatment
      protocol based on geserelin depot + gonadotropin proved to be more efficacious.

PMID- 7630518
TI  - Career derailments and disappointments.

PMID- 7630517
TI  - [Transvaginal absorption of an oleic solution of progesterone (Gestone) in
      fertile women].
AB  - Transvaginal absorption of a progesterone (P) oleic formulation, commercially
      available for intramuscular administration (Gestone, Amsa, Rome), has been
      investigated in five fertile women in the follicular phase. The contents of a
      vial, corresponding to P 100 mg, was administered intravaginally by a syringe
      connected to an atraumatic cannula inserted in the vagina. While administering
      and for a further 10 minutes the woman remained in the recumbent position. Blood
      samples for P assay were drawn at the following times: 0, 15, 30, 45, 60, 120,
      240, 360, 480 and 1440 minutes. Mean CMax was 5.08 +/- 1.66 ng/ml, and the
      difference between baseline and CMax values was statistically significant (p <
      0.01). TMax resulted as 60 minutes (range 45-240 minutes). Mean serum levels
      lowered subsequently but resulted as still significantly higher than baseline (p
      < 0.05) after 1440 minutes. Mean AUC 0-1440 value was 4236.75 ng h/ml. Any local
      or systemic side-effects were noted. No evidence of vaginal irritation was
      observed in any women. On the basis of the present data it is possible to suggest
      that a twice daily administration schedule could ensure suitable P serum levels
      in fertile women.

PMID- 7630519
TI  - First-line nurse managers in rural hospitals: perceptions of career success.
AB  - First-line nurse managers in small rural hospitals are essential to
      organizational survival, yet little is known about such individuals. A pilot
      study comparing demographic characteristics and career success perceptions of
      first-line nurse managers from rural settings with doctorally prepared nurses
      found that despite age and educational differences, personal characteristics
      identified as contributing to career success were remarkably similar in both
      groups. First-line nurse managers generally credited family members with greater
      degrees of career influence than did their more educated colleagues. However,
      both groups saw themselves as primarily responsible for their own career success.
      This information may assist rural hospitals and nursing personnel to enhance
      their strategic position in the unstable environment of health care reform.

PMID- 7630520
TI  - Nurse executive job loss: trauma or transition.
AB  - Since the enactment of TEFRA, the health care industry has initiated cost-cutting
      measures that have resulted in increased job vulnerability for all levels of
      health care managers. Research on managers and professionals suggests that there
      are categories of factors that moderate the stress of job loss such that career
      growth can occur. Interviews with 10 nurse executives who had experienced
      involuntary turnover suggest a variety of coping strategies that can help to turn
      job loss into a successful career transition.

PMID- 7630521
TI  - Derailment: success and failure.
AB  - Today's career executive faces the challenges of the health care industry and the
      challenges of managing one's own career. The ability to accurately assess one's
      own career and use that knowledge to plan future career strategies is essential.
      This article gives many practical hints for career success.

PMID- 7630522
TI  - Nurse manager personal traits and leadership characteristics.
AB  - A portion of an Organizational Dynamics Paradigm provided the framework for
      examining urban hospital nurse managers' personality and staff nurses'
      perceptions of their leadership. Nurse managers' personality traits were
      comparable to American women in general. On motivation to manage they scored
      lower than business and health services managers and higher than female public
      school administrators. Staff nurses rated managers favorably on leadership style,
      power, and influence. Personality was linked modestly to motivation to manage and
      selected aspects of leadership.

PMID- 7630523
TI  - An expanded role for nurses: point, counterpoint, and an action plan for success.
AB  - Changes in the health care system have prompted an expansion of the traditional
      role of nurses in health care institutions. Adapting to this expansion requires a
      new vision of nursing, new learning, and a willingness to proactively embrace the
      inevitable revolution in health care. The action plan for nurses set forth in
      this article outlines eight practical steps for successfully navigating the
      turbulent waters of changes associated with role expansion.

PMID- 7630524
TI  - The power of place: career transformation through stability.
AB  - Activities surrounding mergers, acquisitions, and right-sizing are calling
      nursing leaders to make life-giving choices for both their organizations and
      themselves. Career decisions are intimately woven into the philosophical frame
      and personal reality of each leader. Some choose to move in vast spaces, which
      create a career that is broad and sweeping both geographically and
      experientially. Others stay in place and facilitate their place in the universe
      through stability and connection. This article examines a career and leadership
      experience of a nurse executive who has remained in one geographical space for
      her entire life. Opportunities and challenges of this career path are explored
      while life-giving strategies that create meaning and significance for self and
      others are identified.

PMID- 7630525
TI  - The nurse executive as multiple frame manager.
AB  - Determining the skills a nurse executive needs to be successful in today's
      changing health care market continues to be a popular focus for discussion and
      research. The use of multiframe organizational management, an approach previously
      unexplored with nurse executives, was the focus of a qualitative research study
      with five nurse executives practicing in a large midwestern metropolitan area.
      The study not only revealed how nurse executives use this skill in their everyday
      practice, but also provided a profile of how one nurse executive uses multiframe
      organizational management.

PMID- 7630526
TI  - Career transitions of the nurse executive.
AB  - Health care organizations of today are in rapid transition with changes in roles,
      structures, and expectations. These circumstances may find those in patient care
      and nursing executive roles either choosing to leave their challenging and
      stressful positions or receiving the message that the organization no longer
      desires to have the employment relationship continued. The career adjustments are
      many and often difficult for those who have spent a lifetime to reach the
      executive level. Successful strategies during this time of transition are
      critical for continued and successful careers.

PMID- 7630527
TI  - Thriving in chaos: personal and career development.
AB  - The rapidly changing workplace demands that people who manage their careers
      explore the dangers and the opportunities for themselves personally. This
      includes accepting the reality of the current environment that indicates 50
      percent of the eight jobs an average American will hold will terminate
      involuntarily. Grieving about previous life and job expectations may be necessary
      to take advantage of the extensive opportunities available. Developing,
      implementing, and evaluating a life and career plan are essential to thriving in
      this chaos.

PMID- 7630529
TI  - Getting wired for success.

PMID- 7630528
TI  - Nurse executives: career derailment, success, and dilemmas.
AB  - Nurse executives are facing the complexity of orchestrating their leadership
      roles within a sea of turbulence. The realities of organizational change pose
      both threats and opportunities for career success or derailment. Understanding
      the realities is critical to success.

PMID- 7630530
TI  - Moving student clinical experiences into primary care settings.
AB  - Many baccalaureate nursing faculty members are seeking community-based
      experiences for their students in response to anticipated changes in the
      healthcare delivery system. The author describes how one nursing program has
      initiated experiences for students in a rural primary healthcare clinic.

PMID- 7630531
TI  - Examination scores: block teaching versus traditional teaching.

PMID- 7630532
TI  - Community health nursing in migrant farm camps.
AB  - The author describes a community health nursing experience in the migrant farm
      camps of south Georgia. While providing primary healthcare to an underserved
      migrant farm community, students began to understand the complexities of health,
      policy, and community organization. Examples are presented that reflect crucial
      elements of student involvement and barriers to learning.

PMID- 7630533
TI  - Burnout in undergraduate nursing students.
AB  - Quantitative research using the Maslach Burnout Inventory has revealed that
      nursing students experience burnout and that their levels of burnout are
      comparable to working nurses. To explore the meaning of burnout as experienced by
      nursing students, a phenomenological research design was used. Once the essence
      of nursing students' experience of burnout is discovered, faculty members can
      design strategies targeted at the specific themes that emerged to help prevent
      burnout in their students. Twenty-eight sophomore nursing students described a
      situation in which they had experienced burnout during their nursing program.
      Using Colaizzi's phenomenological method, the following nine theme clusters
      emerged: engulfing demands, time pressure, no outlet, physically debilitating,
      emotionally overwhelming, lack of concentration, decreased motivation, impeding
      relationships, and coping attempts. Implications for nurse educators are
      addressed, along with specific interventions to help prevent burnout in
      undergraduate nursing students.

PMID- 7630534
TI  - The Toymakers: an application activity.
AB  - Novel teaching strategies can help students recognize and experience, firsthand,
      the relevance of course content for clinical practice. The Toymaker Activity
      challenged students in a pediatric nursing course to use principles of growth and
      development in a creative and practical way. Student participation and feedback
      demonstrated successful application and improved understanding of the impact of
      growth and development in the nursing care of children.

PMID- 7630535
TI  - Cooperative learning strategies: an effective method of teaching nursing
      research.
AB  - Convinced that both learning the research process and conducting research can be
      intellectually satisfying, cooperative learning strategies were employed in a
      research course taught to undergraduate nursing students. The author describes
      how formal and informal cooperative learning groups were used to facilitate
      learning and the development of clinical experimental and quasi-experimental
      research designs for students' research posters and presentations.

PMID- 7630536
TI  - The use of lecture as a teaching strategy.

PMID- 7630537
TI  - Nutrition-related activities of entry-level nurses.

PMID- 7630538
TI  - Designing class participation experiences for the introverted student.
AB  - Class participation for students is such a common expectation of nurse educators
      that it is easy to overlook the need to tailor class participation activities to
      individual student needs. An understanding of the various temperaments of
      individuals, especially preferences related to extroversion and introversion, can
      help nurse educators to plan class participation experiences that foster skills
      in critical thinking and enhance personal growth.

PMID- 7630539
TI  - Innovative teaching of developmental themes of the elderly and the young.
AB  - The authors demonstrate how faculty members creatively designed an undergraduate
      course in which students learned developmental similarities and differences
      across the life span. Student-client interaction, involvement in practice, and
      inquiry strategies are used to enhance teaching and learning. Practice informed
      theory for students resulting ina meaningful synthesis of content.

PMID- 7630540
TI  - Tic Tac Test Ready.

PMID- 7630541
TI  - Collaborative student and faculty research.
AB  - Nurses with masters degrees and faculty members are expected to conduct research
      as part of their roles. The author discusses how students and faculty complete
      research studies, as colleagues, in a recently accredited graduate nursing
      program in family health nursing.

PMID- 7630542
TI  - Redesigning faculty roles to enhance program outcomes: a case study.

PMID- 7630543
TI  - E-mail links students and faculty.

PMID- 7630544
TI  - Documenting the details.

PMID- 7630545
TI  - Self-test: recognizing signs of shock.

PMID- 7630546
TI  - Using pulse oximeters safely.

PMID- 7630547
TI  - Myths & facts ... about attention deficit disorder.

PMID- 7630548
TI  - Acquiring HIV on the job.

PMID- 7630549
TI  - Minimizing claustrophobia in an MRI scanner.

PMID- 7630550
TI  - Learning about Lyme disease.

PMID- 7630551
TI  - Stabilizing a patient with massive facial injuries.

PMID- 7630552
TI  - Planning care for the patient with breast cancer.

PMID- 7630553
TI  - Taking the confusion out of calcium levels.

PMID- 7630554
TI  - Patient-teaching aid: taking acetaminophen.

PMID- 7630555
TI  - Certification review: understanding cardiovascular disorders.

PMID- 7630556
TI  - A routine rhythm suddenly isn't routine.

PMID- 7630557
TI  - Hemolytic transfusion reaction.

PMID- 7630558
TI  - Why pick a PICC? What you need to know.

PMID- 7630559
TI  - T.I.P.S. for controlling bleeding.

PMID- 7630560
TI  - Bringing Edie "home" to die.

PMID- 7630561
TI  - Caring for patients with meningitis.

PMID- 7630562
TI  - Selecting the best dressing sponge.

PMID- 7630563
TI  - Adenosine: a quick fix for PSVT.

PMID- 7630564
TI  - Ventilator alarms: how to respond with confidence.

PMID- 7630565
TI  - New diabetes nutrition guidelines: do you know the score?

PMID- 7630566
TI  - A gift to remember.

PMID- 7630567
TI  - Controlling pain in the elderly.

PMID- 7630569
TI  - Choosing your mentor.

PMID- 7630568
TI  - Becoming a mentor.

PMID- 7630570
TI  - Taking the "right" side.

PMID- 7630571
TI  - Hormonal and Neural Modulation of Physiological and Behavioral Function.
      Proceedings of a satellite symposium of the 3rd International Behavioral
      Neuroscience Conference. Clearwater Beach, Florida, May 19, 1994. Honoring Julian
      M. Davidson, professor emeritus Stanford University School of Medicine.

PMID- 7630572
TI  - Regulation of atrial natriuretic factor secretion and expression in the ovine
      fetus.
AB  - The cardiac hormone atrial natriuretic factor (ANF) is present in the fetal
      circulation at high concentrations and exceeds that in the maternal circulation.
      Administration of exogenous ANF into the near-term ovine fetus lowers arterial
      pressure and reduces blood volume. The fetal kidney responds to ANF with a
      diuresis and natriuresis. The physiological stimuli which modulate ANF secretion
      in the fetus include vascular volume expansion, hyperosmolality and hypoxia, with
      hypoxia being the most potent stimulus. In addition, endothelin administration
      into the fetus increases plasma ANF concentrations. The fetal atria appears to be
      the primary site of ANF synthesis, although the ventricles also produce ANF. The
      expression of ANF peptide and its messenger RNA in the fetal atria and ventricles
      demonstrate a developmental pattern. Thus, the secretion of ANF may be mediated
      by factors such as endothelin and may be augmented by stimuli such as hypoxia
      which acts through induction of cardiac ANF gene expression.

PMID- 7630573
TI  - Sex hormone-binding globulin and male sexual development.
AB  - The masculinization of the brain, reproductive tract and many other structures is
      critically dependent on the testicular hormone, testosterone (T). In many
      species, T circulates bound with high affinity to sex hormone-binding globulin
      (SHBG). This protein has a wide phylogenetic distribution and SHBG or SHBG-like
      proteins are produced by the liver, testes, placenta, brain and other tissues.
      SHBG activity is detectable during gestation and its expression is both stage-
      and tissue-dependent. Although SHBG binds circulating androgens, it is argued
      that the trapping of steroids in the circulation is not the principal function of
      this protein. The specific binding and uptake of SHBG by various tissues has been
      observed and suggests that SHBG may directly affect the delivery of androgen
      signals to target tissues. Effects of SHBG on androgen metabolism, tissue
      retention, cellular targeting, and action are reviewed. Evidence to date
      indicates that SHBG is able to enhance or inhibit the uptake of androgens in a
      cell- and tissue-specific manner. Future work will be necessary to demonstrate
      whether such actions of SHBG are important for normal male reproductive
      development.

PMID- 7630574
TI  - Prepubertal testosterone treatment of female rats: defeminization of behavioral
      and endocrine function in adulthood.
AB  - This study assessed the capacity of testosterone (T) administered well after the
      neonatal "critical" period to permanently sexually differentiate reproductive
      function. Females received T filled or empty Silastic capsules during days 15-30
      of age and vaginal cyclicity, ovarian weight and appearance, lordosis and
      proceptive behaviors, mounting behavior, and the gonadotropin response to
      estrogen and progesterone were measured in adulthood. T-treated females (plasma
      levels of 0.66 ng T/ml) showed constant vaginal estrus from the day of vaginal
      opening and small, polyfollicular ovaries. Proceptive behaviors were dramatically
      reduced whether or not the ovaries were present after day 15 of age, but lordosis
      behavior was not affected. Exposure to T for 5-6 h was ineffective. Compared to
      controls, T-treated females had dramatically reduced plasma FSH and LH surges. No
      effects were observed on mounting behavior, phallus size, or body weights. These
      results suggest that androgen at approximately male levels can act on neural
      substrates well beyond the neonatal period to permanently defeminize endocrine
      and behavioral function in the female rat.

PMID- 7630576
TI  - Understanding and diagnosing sexual dysfunction: recent progress through
      psychophysiological and psychophysical methods.
AB  - The psychophysiological method has been applied to the study of human sexual
      response for well over three decades. The value of this method in providing an
      objective, integrated approach to the understanding of sexual response, and more
      specifically sexual dysfunction, is presented. Selected results from recent
      studies using this methodology illustrate the complex relationships that emerge
      among cognitive, affective, and physiological components of the sexual response.
      In addition, data from a systematic study of the use of psychophysiological
      procedures as an aid in differential diagnosis are given as evidence that this
      methodology offers a further strategy for assessing problems such as erectile
      dysfunction and premature ejaculation. Finally, recent findings utilizing sensory
      psychophysical procedures which relate subjective penile thresholds to sexual
      response and dysfunction are reviewed. Such procedures also study the interaction
      of physical/physiological systems with psychological events, and as such may be
      considered relevant to understanding the relationship between psychological
      aspects of sexual response.

PMID- 7630575
TI  - Prepubertal testosterone treatment of neonatally gonadectomized male rats:
      defeminization and masculinization of behavioral and endocrine function in
      adulthood.
AB  - Testosterone (T) administered well after the neonatal "critical" period to
      females at a dose approximating male levels permanently defeminizes reproductive
      function (see companion publication). To obtain comparable data for the male,
      neonatally gonadectomized (NeoGx) males received T filled or empty Silastic
      capsules during days 15-30 of age and were studied in adulthood. Compared to
      controls, the T treatment resulted in reduced lordosis and proceptive behaviors,
      increased mounting and intromission behaviors without differences in penile
      reflexes or size, and reduced plasma FSH and LH surges. Twenty of twenty-three
      sham-NeoGx males, but only one NeoGx male, showed ejaculatory behavior despite
      equivalence in penile reflexes and size after detaching a frenulum when present
      on the penis. These results show that T can still act on neural substrates well
      beyond the neonatal period to defeminize and masculinize endocrine and behavioral
      function in the male rat. A comparison with effects in females indicates a sex
      difference, the male appearing to be more sensitive to these actions of T.

PMID- 7630577
TI  - Placing erection in context: the reflexogenic-psychogenic dichotomy reconsidered.
AB  - Penile erections are usually classified as arising from "reflexogenic" or
      "psychogenic" causes. In practice this dichotomy has translated, somewhat
      circularly, to a distinction between spinal vs. supraspinal mediation, pelvic vs.
      hypogastric neural mediation, and perineal somesthetic stimulation vs.
      stimulation of receptors innervated by the cranial nerves. Evidence for
      differential regulation of erection in different contexts is reviewed. Research
      ascribing a physiological role to the hypogastric nerves in psychogenic erection,
      exemplified by classic studies of cats and spinally injured men, is suggestive
      but not compelling. Somewhat stronger is evidence that erection in some contexts
      (e.g., nocturnal penile tumescence (NPT) in humans or touch-stimulated erection
      in rats) is more sensitive to androgen levels than in other contexts (e.g.,
      visual erotic stimuli in men or copulation in rats). However, some of these
      differences may arise from the relative erectogenic strength of the stimuli,
      rather than from qualitative differences in androgen sensitivity of different
      contexts. More compelling is the possibility that conflicting interpretations of
      the role of dopamine in erection may stem in large part from differences among
      laboratories in the context in which erection is evoked. In light of the evidence
      reviewed, it seems unlikely that the conventional reflexogenic-psychogenic
      dichotomy should be retained, at least in its present form. As a first step, it
      may be worth considering that reflexive erections may not be limited to
      somesthetic perineal stimulation, but rather may also include stimuli received
      via the cranial nerves. Two alternatives to the standard reflexogenic-psychogenic
      dichotomy are proposed. The first is a minor revision in which two senses of
      psychogenic erection are distinguished: the weak, commonly used, sense would
      include erection resulting from any extrinsic nonsomesthetic stimulation, whether
      visual, auditory, or chemosensory. In this sense, reflexive erections and
      psychogenic erections may not be mutually exclusive. The strong sense of
      psychogenic erection would be limited to memory and fantasy. The origins of
      psychogenic erection in both senses need not be available to consciousness, which
      may account for apparently spontaneous erections. In the second alternative
      taxonomy, erectogenic stimuli are classified as contact (somesthetic) or
      noncontact, and their action in evoking erection is placed on a continuum of
      reflexivity. Erectile contexts could then be considered as orthogonal to the
      other two dimensions. Even without a change in taxonomy, the conduct and
      interpretation of research into erectile function may be expected to benefit from
      closer attention to differences and similarities between contexts and species,
      and to context-sensitive differences in the regulation of erection.

PMID- 7630578
TI  - Cardiac vagal tone: a physiological index of stress.
AB  - Cardiac vagal tone is proposed as a novel index of stress and stress
      vulnerability in mammals. A model is described that emphasizes the role of the
      parasympathetic nervous system and particularly the vagus nerve in defining
      stress. The model details the importance of a branch of the vagus originating in
      the nucleus ambiguus. In mammals the nucleus ambiguus not only coordinates
      sucking, swallowing, and breathing, but it also regulates heart rate and
      vocalizations in response to stressors. In mammals it is possible, by quantifying
      the amplitude of respiratory sinus arrhythmia, to assess the tonic and phasic
      regulation of the vagal pathways originating in the nucleus ambiguus. Measurement
      of this component of vagal tone is proposed as a method to assess, on an
      individual basis, both stress and the vulnerability to stress.

PMID- 7630579
TI  - Limbic pathways and hypothalamic neurotransmitters mediating adrenocortical
      responses to neural stimuli.
AB  - One of the major phenomena related to the stress response is the activation of
      the hypothalamo-pituitary-adrenocortical (HPA) axis. This axis consists of
      corticotropin releasing factor-41 in the paraventricular nucleus of the
      hypothalamus (PVN), which in response to a variety of stimuli is released into
      the portal circulation and stimulates pituitary ACTH secretion and subsequently
      adrenocortical discharge. The mechanisms involved in the activation are not
      uniform and the responses to various stimuli are mediated by different neural
      pathways. Since extrahypothalamic limbic structures play a significant role in
      the HPA function, it is the purpose of this review to describe the neural
      pathways between the hippocampus, septum and amygdala and the hypothalamus in
      relation to adrenocortical activity and the differential role of the medial
      forebrain bundle as well as the effects of various hypothalamic deafferentation
      on the transmission of the neural impulses to the hypothalamus. Also, the
      importance of norepinephrine and serotonin in the activation of the HPA axis will
      be delineated.

PMID- 7630581
TI  - Role of VIP in the regulation of LH secretion in the female rat.
AB  - Vasoactive intestinal peptide (VIP) is found within neurons throughout the body.
      It influences the secretion of several hormones of the anterior pituitary by
      neural and pituitary actions. We review work from our laboratory that indicates
      that VIP inhibits the secretion of luteinizing hormone (LH) by a hypothalamic
      action. Experiments involving neural lesions indicate that VIP acts on the
      receptor field in the paraventricular nuclei of neurons whose cell bodies are
      located in the suprachiasmatic nuclei. The effect on LH secretion is subsequently
      mediated by a nonVIPergic pathway, which does not appear to involve either
      dopamine or endogenous opioids. Experiments with the specific VIP antagonist,
      [4Cl-D-Phe6,Leu17]VIP, indicate that the actions on LH secretion of VIP and of
      the related peptides, growth hormone-releasing hormone and secretin, are mediated
      by VIP-preferring receptors. VIP also blocks the steroid-induced LH surge in the
      ovariectomized rat. The VIP antagonist induces a significant, but small increase
      in LH secretion in the intact rat, indicating that VIP has a modulatory, rather
      than deterministic, role in the regulation of LH secretion.

PMID- 7630580
TI  - Reproduction and the renin-angiotensin system.
AB  - A unique aspect of the circulating renin-angiotensin system and the many
      independent tissue renin-angiotensin systems is their interactions at multiple
      levels with reproduction. These interactions, which have received relatively
      little attention, include effects of estrogens and possibly androgens on hepatic
      and renal angiotensinogen mRNA; effects of androgens on the Ren-2 gene and
      salivary renin in mice; the prorenin surge that occurs with but outlasts the LH
      surge during the menstrual cycle; the inhibitory effects of estrogens on thirst
      and water intake; the tissue renin-angiotensin systems in the brain, the anterior
      pituitary, and the ovaries and testes, that is, in all the components of the
      hypothalamo-pituitary-gonadal axis; the presence of some components of the renin
      angiotensin system in the uterus and the fetoplacental unit; and the possible
      relation of renin and angiotensin to ovulation and fetal well-being. These
      interactions are described and their significance considered in this short
      review.

PMID- 7630582
TI  - Neurobiological correlates of masculine sexual behavior.
AB  - The experimental analysis of the neuroendocrine interactions regulating sexual
      behavior has traditionally relied on studying the effects of CNS lesions and
      pharmacological treatments with hormones or drugs purportedly acting through
      specific neurotransmitter systems. New methodological developments have allowed
      the assessment of several indices of neural function in experimental animals,
      particularly the rat, as they relate to behavioral changes. In the field of
      sexual behavior, ex vivo analyses have been used to measure markers of energy
      metabolism, such as 2-deoxyglucose uptake and Na,K-ATPase activity, the tissue
      content of neurotransmitters and metabolites, the levels of steroid receptors and
      neurosteroids, and immediate-early gene expression products in different areas of
      the CNS. In vivo studies have monitored brain electrical activity and
      temperature, as well as the extracellular levels of neurotransmitters and
      metabolites by cerebrospinal fluid sampling, push-pull perfusion and, especially,
      electrochemical recordings and microdialysis, in the course of mating and
      exposure to various relevant stimuli. The findings with the different
      methodologies are generally consistent and agree with those of previous surgical
      and pharmacological manipulations. They provide data on temporal relationships
      between neurobiological and behavioral events and suggest new interpretations for
      different aspects of the male copulatory pattern.

PMID- 7630583
TI  - Sexual function in altered physiological states: comparison of effects of
      hypertension, diabetes, hyperprolactinemia, and others to "normal" aging in male
      rats.
AB  - In this review, we examine the changes in sexual function that accompany
      deviations from "normal" physiological states. We propose that the changes one
      observes in many altered physiological states should not be viewed in isolation.
      We describe our paradigms for assessing sexual function, and proceed to evaluate
      how sexual function changes with hormonal deprivation and aging, in rat models
      for hypertension, in severe hyperprolactinemia, in streptozotocin-induced
      diabetes, after chronic alcohol intake, after chronic morphine administration,
      and after exposure to the heavy metal, cadmium. We will provide evidence for the
      involvement of adrenergic transmitters and two neuropeptides, neuropeptide Y and
      somatostatin, in the neuroendocrine regulation of sexual behavior. Finally, we
      compare and contrast the changes observed relative to the changes seen in
      "normal" aging in rats. The sequence of age-related changes in sexual function is
      distinct. The first change observed is a decrement in ex copula erectile
      reflexes. Next are decreases in ejaculatory threshold, followed shortly by
      increases in initiation and reinitiation of copulation after ejaculation. This is
      followed by a decrement in the number of males copulating to ejaculation.
      Finally, there is a failure to initiate the copulatory process. This sequelae is
      relatively common, being evident after castration, with hyperprolactinemia, and
      after exposure to cadmium. The data available for sexual function in hypertension
      is incomplete and modified by the etiology, but a suggestion for this sequelae is
      seen in SHR. In contrast, sexual dysfunction associated with chronic morphine
      administration appears to be due to an initial deficit in motivational aspects.
      Testosterone reverses sexual dysfunction associated with castration, but not with
      idiopathic sexual inactivity, nor with sexual dysfunction associated with aging,
      diabetes, or chronic morphine administration. Comparing sexual function in rat
      models for hypertension, diabetes and chronic ethanol leads to the conclusion
      that increases in blood pressure, like decreases in testosterone, cannot be the
      primary causal factor for sexual dysfunction. Age, hormonal history of the
      subject, and the age at castration influence changes in sexual function. Age
      related sexual dysfunction appears to be contributed to by changes in adrenergic
      neuropeptidergic, to include sympathetic, systems. Site-specific administration
      of NPY induces alterations in parameters of copulatory behavior which mimic those
      seen in aging and the retention of ejaculatory behavior with aging is associated
      with site-selective attenuation (or reversal) of age-associated changes in NPY
      content. Yohimbine enhances copulatory activity in castrated and aging rats, and
      attenuates or reverses the antisexual effects of clonidine, epinephrine and
      somatostatin.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7630584
TI  - Physiological substrates of mammalian monogamy: the prairie vole model.
AB  - Prairie voles (Microtus ochrogaster) are described here as a model system in
      which it is possible to examine, within the context of natural history, the
      proximate processes regulating the social and reproductive behaviors that
      characterize a monogamous social system. Neuropeptides, including oxytocin and
      vasopressin, and the adrenal glucocorticoid, corticosterone, have been implicated
      in the neural regulation of partner preferences, and in the male, vasopressin has
      been implicated in the induction of selective aggression toward strangers. We
      hypothesize here that interactions among oxytocin, vasopressin and
      glucocorticoids could provide substrates for dynamic changes in social and
      agonistic behaviors, including those required in the development and expression
      of monogamy. Results from research with voles suggest that the behaviors
      characteristics of monogamy, including social attachments and biparental care,
      may be modified by hormones during development and may be regulated by different
      mechanisms in males and females.

PMID- 7630585
TI  - Oxytocin and rodent sociosexual responses: from behavior to gene expression.
AB  - In most mammals, gonadal steroid hormones are required for the expression of
      species-typical reproductive behavior. Over the past few years it has become
      evident that neuropeptides, such as oxytocin (OT) and vasopressin (AVP), also
      play a key role in the regulation of both social and sexual behavior. Through
      studies of gonadal steroid/neuropeptide interactions, we have been able to
      discover species differences in behavioral and physiological responses to OT that
      may be associated with species-specific distributions of OT receptors or
      differential levels of OT gene expression in the central nervous system (CNS).
      However, the characterization of OT's behavioral effects has been conducted
      primarily in rats and the neural mechanisms underlying these behaviors are not
      clearly understood. The present paper will describe and discuss the biological
      significance of OT-mediated behavioral responses in both female and male prairie
      voles and rats, speculate on the neural mechanisms (OT receptor regulation) and
      reproductive physiology involved in species-specific sociosexual behavior, and
      present new methodologies for studying signal transduction mechanisms involved in
      OT gene expression in the CNS.

PMID- 7630586
TI  - Are the effects of androgens on male sexuality noradrenergically mediated? Some
      consideration of the human.
AB  - The effects of androgens on the sexuality of male rodents is likely to be
      mediated, at least in part, by central noradrenergic (NA) mechanisms. Davidson's
      group has shown this by restoring behaviour in castrated males with alpha-2
      adrenoceptor antagonists. As yet, there are no comparable studies of drug
      administration to hypogonadal men, but relevant evidence from recent studies in
      eugonadal men is considered. The evidence is consistent with a role for NA
      mediation in human sexual arousal, but suggests that more than one NA mediated
      system exist, involving both central arousal and inhibition of peripheral
      responses such as erection. The study of spontaneous erections during REM sleep
      is of particular interest, as REM is accompanied by virtual cessation of
      peripheral sympathetic activity in relevant parts of the body. "Psychogenic"
      erectile dysfunction may involve a high level of central alpha-2 inhibitory tone
      which reduces the capacity for central arousal. On the other hand, there may be
      an age related loss of responsiveness to the central arousing effects of NA,
      suggesting that the aetiology of psychogenic erectile dysfunction may vary with
      age. NA mechanisms may well be involved in the mediation of androgenic effects in
      humans, but no simple relationship between NA and sexual response should be
      expected.

PMID- 7630587
TI  - Methodological review and meta-analysis of sexuality and menopause research.
AB  - A selection of empirical studies from 1972-1992 that assessed sexuality and the
      peri/post menopausal women were collected and reviewed. Using a blind procedure,
      two Ph. D. experimental psychologists rated methodology sections of all studies.
      For comparison, variables that were related to peri/postmenopausal sexuality were
      converted to a standard effect size and correlation. Significantly higher effects
      sizes were found in studies that were rated as having an adequate measure of
      hormone status or adequate hormone manipulation, included appropriate controls,
      and had less confounding variables. Larger effect sizes tended to be found for
      studies that had an adequate measure of sexuality. Ratings of representativeness
      of the population, number of subjects, age of the subjects, adequacy of the
      menopause measure or statistical analysis were not related to effect sizes.
      Multiple regression analysis showed that overall ratings accounted for 31% of the
      variance of effect sizes. For studies in which an effect size could be calculated
      a mean D of 0.67 +/- 1.23 (SD) was found indicating that hormones, both exogenous
      and endogenous, have some importance to peri/postmenopausal sexuality.
      Difficulties encountered in attempting a meta-analysis in this area and the
      meaning of the findings are discussed, as is the importance of such an analysis
      to the area of sexuality and menopause research.

PMID- 7630588
TI  - To speak in chords about sexuality.
AB  - Sexuality emerges from the interdependencies of biology, awareness, and the facts
      and artifacts of public life. A useful metaphor is that correct accountings of
      sexuality are not one-finger melodies--they are chords. Unfortunately, the
      physical vs. mental and nature vs. nurture controversies remain alive, well, and
      mischievous in regard to the correct understanding of human sexuality. Active
      political and legal disputes about homosexuality exemplify a continuing reliance
      on reductionistic models of the causes of conduct. Discourse relying on public
      misapprehension about biological causality can alter the course of subsequent
      science and public opinion and thus affect personal experience as well. Both
      dualistic and reductionistic models are traps and bar progress; the models should
      not be smuggled into accounts of sexuality.

PMID- 7630590
TI  - The changing managed care arena: impact on subacute care.

PMID- 7630589
TI  - Medicare: unmanaged and going broke.

PMID- 7630591
TI  - Trends in health-care computing according to CIOs.

PMID- 7630592
TI  - Obstetrical liability update--Part II.

PMID- 7630593
TI  - Managing a culturally diverse workforce.
AB  - The cultural beliefs that exist within a group of nurses influence nursing
      practice and communication outcomes. Addressing cultural issues begins by
      identifying personal beliefs and behaviors that are linked to an underlying
      cultural core. A framework for culturally congruent nursing management leads to a
      point of understanding and respect for differences, values, beliefs and
      behaviors.

PMID- 7630594
TI  - Mastering the art of delegation.
AB  - Delegation, an important, readily acquired management skill, promotes efficiency,
      increases productivity and improves time management. A four-step process guides
      the nurse manager through the art and science of delegation.

PMID- 7630595
TI  - Professional development: factors that motivate staff.
AB  - Although many studies identify theories on learning motivation, few analyze
      motivating factors and barriers from the staff nurse perspective. A study
      involving RNs from a pediatric and an intensive care nursing service reveals
      factors that influence or restrain nurses from participating in professional
      activities.

PMID- 7630596
TI  - Home infusion therapy: meeting a need.
AB  - A home infusion program for a midsize hospital was developed to meet the needs of
      patients discharged on specific infusion therapies. The program's history,
      development, credentialing, referral and QA/QI process are described. The
      infusion nurse provides in-hospital teaching, discharge coordination, and follow
      up at home while working with physicians, social workers, hospital nurses and
      home-infusion-therapy providers.

PMID- 7630597
TI  - Delegating to a transcultural team.
AB  - Six cultural phenomena must be considered when delegating to staff with a
      culturally diverse background. Communication, space, social organization, time,
      environmental control and biological variations encourage an understanding of
      unique cultural values, beliefs and practices.

PMID- 7630598
TI  - Empowering women: improving a community's health.
AB  - Community Health Aides (volunteers) were trained to become health resource
      persons in their own community. The curriculum for the training sessions was
      modeled after the Camp Health Aide Program, which is based on the belief that
      with information and support, migrant farmworkers can make changes in their lives
      and environment to improve their health and the community's health.

PMID- 7630599
TI  - Transformational leadership in health care.
AB  - One of the most important evolutionary forces in transforming health care is the
      shift from management to leadership in nursing. The transformational leader will
      be the catalyst for expanding a holistic perspective, empowering nursing
      personnel at all levels and maximizing use of technology in the movement beyond
      even patient-centered health care to patient-directed health outcomes.

PMID- 7630600
TI  - The head nurse role in a rural hospital.
AB  - The role of the head nurse in a rural hospital is examined to identify
      perceptions of role conflict and role ambiguity experienced by head nurses. Study
      results suggest that improving staffing patterns, increasing the number of
      registered nurses, eliminating non-nursing activities and management training are
      warranted. The director of nursing plans to enhance the head nurse role and to
      facilitate further decentralization of nursing services.

PMID- 7630601
TI  - Addressing chemical dependency: a need for consistent measures.
AB  - A study surveyed RNs and LPNs who had been involved in the Board of Nursing's
      discipline process for chemical dependency. The association between the type of
      disciplinary action taken and the perceived benefits to recovery are rated.

PMID- 7630602
TI  - Redesigning patient care delivery: being at the bleeding edge!
AB  - Processes for total quality management, redesigning of patient care delivery and
      differentiated practice in nursing were developed and implemented simultaneously
      on two nursing units. This article describes the activities of the steering team
      and three work groups through the first nine months of implementation.

PMID- 7630603
TI  - Promoting comfort and relieving pain in dying patients.

PMID- 7630604
TI  - Leaders compete for national fellowships and internships.

PMID- 7630605
TI  - Doctor godfather.

PMID- 7630606
TI  - Cultural diversity: health belief systems.

PMID- 7630607
TI  - Evaluation by portfolio.

PMID- 7630608
TI  - Solution oriented management: an alternative approach.

PMID- 7630610
TI  - Assessing competencies of the nursing assistant.

PMID- 7630609
TI  - Changing jobs: making the right decisions.

PMID- 7630611
TI  - Battered staff syndrome: a conspiracy of silence?

PMID- 7630612
TI  - Change: the inevitable constant.

PMID- 7630613
TI  - Decreasing occupational back injuries.

PMID- 7630614
TI  - JCAHO is coming!

PMID- 7630615
TI  - A method of image analysis for primary angle closure glaucoma.
AB  - The anterior segment of the eye is displayed on the video monitor using a
      slitlamp apparatus (slitlamp 75SL, Zeiss, Germany) combined with a video camera
      and the video image is then analyzed with a computer to convert the optimal image
      into the true image. The profile of the true image of the anterior eye segment
      allows us to estimate the pupil-blocking force, which is the posteriorly directed
      vector exerted in the iris tissue, according to Mapstone's theory. In mensuration
      by digitizer on 3 occasions from a single video image of a given normal eye, the
      Pbf was -0.0255 +/- 0.0011 lambda (= Young's module). And the pupil-blocking
      force of 10 procedures in a given glaucomatous eye was +1.092 +/- 0.018 lambda.

PMID- 7630616
TI  - Colour Doppler imaging to evaluate the action of a drug in ocular pathology.
AB  - Colour Doppler imaging is a recent advance in ultrasonography. It allows
      simultaneous two-dimensional imaging of structures and evaluation of blood flow.
      Retinal vascular pathologies, macular degeneration, endobulbar tumours, and
      ischaemic vascular diseases can be analyzed by colour Doppler imaging. Moreover,
      it offers the possibility of evaluating the vascular effects of a drug and to
      monitor them in time. We have, therefore, carried out a study using colour
      Doppler imaging to evaluate a drug capable of acting on the vascular wall in
      patients with macular degeneration or diabetic retinopathy. The results show that
      this drug, obtained by enzymatic hydrolysis of bovine factor VIII (Vueffe;
      Laboratory Baldacci S.p.A., Pisa, Italy), induces a significant increase in blood
      flow and in retinal central artery systolic speed.

PMID- 7630617
TI  - Effects of self-relaxation methods and visual imagery on IOP in patients with
      open-angle glaucoma.
AB  - In this study, the effects of a training in relaxation and visual imagery on the
      intra-ocular pressure (IOP) of patients with primary open-angle glaucoma were
      investigated. Twenty-three patients, aged 24-69 years, were assigned either to a
      training group or to a waiting-list control group. The intervention included a
      basic programme (BP) of standard autogenic relaxation exercises and an advanced
      programme (AP) in which special exercises in ocular relaxation and imagination of
      aqueous humour drainage were conducted. IOP was measured before and after each
      training session. Twenty-four-hour IOP profiles were ascertained, and the water
      drinking test to provoke maximum IOP levels was performed during clinical
      assessments prior to the training, between the BP and the AP and after
      termination of the training. Results indicate only slight short-term changes of
      IOP levels immediately after each training session. However, during the course of
      the BP as well as of the AP a relevant decrease in IOP could be measured. Twenty
      four-hour IOP profiles as well as the water drinking test also showed significant
      reductions of IOP during time. Medication could be reduced for 56% of the
      initially treated patients. The findings suggest that relaxation and visual
      imagery techniques can be beneficial in reducing elevated IOP levels in patients
      with open-angle glaucoma though the conclusiveness of the data is limited due to
      methodological shortcomings.

PMID- 7630618
TI  - Influence of posture on the visual field in glaucoma patients and controls.
AB  - The intra-ocular pressure rises when body position is changed from sitting to
      supine. This phenomenon occurs to the same extent in healthy people and glaucoma
      patients. The purpose of this preliminary study was to determine the effect of
      posture on the visual field. Visual fields of 15 eyes of 12 normal-tension
      glaucoma (NTG) patients, 16 eyes of 11 high-tension glaucoma (HTG) patients and
      30 eyes of 26 healthy controls were measured in the upright and supine positions
      with program G1X on an Octopus swivel-arm perimeter. The delta mean defect (delta
      MD), that is MDupright-MDsupine, was calculated for each patient and compared
      among study groups. Whereas visual fields improved in healthy controls (delta MD
      = +0.45 dB), glaucoma patients showed a slight deterioration of the visual field
      after changing position from supine to upright (HTG: delta MD = -0.25 dB, NTG:
      delta MD = -0.24 dB). The difference between HTG and controls, as well as between
      NTG and controls, was statistically significant (p < 0.002, Student's t test).
      These findings indicate that in some glaucoma patients the regulatory mechanisms
      for blood supply in the optic nerve head are insufficient.

PMID- 7630619
TI  - Gonioscopic evaluation of glaucoma patients after trabeculectomy.
AB  - Seventy-three eyes of 65 patients with various types of glaucoma have been
      evaluated before and after trabeculectomy. These cases have been examined
      gonioscopically preoperatively and in the 1st, 3rd, and 6th months. The status of
      the trabeculectomy defect, and synechiae related to the area, factors
      predisposing to the development of synechiae, have been looked at. Peripheral
      anterior synechia formation was more pronounced in chronic angle closure
      glaucoma, exfoliative glaucoma and secondary glaucoma. The relationship between
      synechiae and intraocular pressure has been defined. The eyes with total
      peripheral anterior synechia had a lesser degree of success in lowering the
      intraocular pressure.

PMID- 7630620
TI  - Effects of strabismus surgery on refraction in children.
AB  - We assessed 115 eyes of 59 children with esotropia 2-3 months postoperatively to
      evaluate the effects of strabismus surgery on refraction. Three variables were
      measured: spherical equivalent, and cylinder power and axis. The mean changes in
      spherical equivalent were non-significant. The axis of postoperative astigmatism
      moved towards 'with-the-rule', thus improving refraction. The amount of recession
      and the consequent changes in cylinder power were inversely related. The results
      showed a significant change in cylinder axis after recession of the inferior
      oblique. Recession-tucking procedures led to the largest changes in cylinder
      power.

PMID- 7630621
TI  - Aqueous flare and retinal capillary changes in eyes with diabetic retinopathy.
AB  - We examined 112 eyes of 112 adult-onset diabetic patients by fundus fluorescein
      angiography and with the laser flare cell meter (LFCM) in order to evaluate the
      possible correlation between retinal capillary changes and aqueous flare.
      Diabetic eyes were divided into the following groups: minor background diabetic
      retinopathy (MDR), nonproliferative diabetic retinopathy with predominant
      capillary occlusion (ONP), nonproliferative diabetic retinopathy with predominant
      capillary dilation and exudation (ENP) and proliferative diabetic retinopathy
      (PDR). 108 age-matched eyes of 108 normal subjects were used as control group.
      Flare values (photon counts/ms) of all diabetic groups (MDR 9.01 +/- 0.79, ONP
      13.66 +/- 3.22, ENP 16.43 +/- 5.55, PDR 18.57 +/- 6.99) were significantly higher
      than in the normal control group (4.28 +/- 1.14, p < 0.0001). Significant
      differences were found between ONP and ENP (p = 0.008) and between ONP and PDR (p
      = 0.0001) but not between ENP and PDR (p = 0.4). Our results indicate that there
      is a correlation between aqueous flare and the type of angiographic retinal
      capillary changes with higher flare values in eyes with retinal capillary
      dilatation and exudation. Measurements with LFCM may be useful to quantify the
      extent and severity of capillary alterations in diabetic eyes.

PMID- 7630623
TI  - Comparative study on topical and oral administration of ofloxacin for Pseudomonas
      corneal ulcer in rabbits.
AB  - Pseudomonas aeruginosa is one of the most frequently isolated microorganisms in
      bacterial corneal ulcers in Japan and other countries. We evaluated a topical
      application of 0.3% ofloxacin (OFLX) for Pseudomonas corneal ulcer in rabbits and
      compared it to the clinical effects of OFLX in topical and oral applications. All
      corneas in the control groups of both experiments showed total leukoma with a
      score of 4 on the seventh day. On the other hand, in the preventive experiment,
      all the scores in the OFLX-treated group were 0, and those in the therapeutic
      experiment were smaller than those of both the control and oral groups. The
      results indicate that topical OFLX is effective on Pseudomonas corneal ulcer in
      rabbits.

PMID- 7630622
TI  - Bovine factor VIII derivative in the treatment of non-proliferative diabetic
      retinopathy.
AB  - The complexity of the pathogenesis of diabetic retinopathy (DR) makes it
      difficult to produce effective drugs for its treatment. Among the active
      principles recently suggested, the peptide fraction of bovine factor VIII of the
      clotting cascade deserves particular attention. Bovine factor VIII derivatives
      (vascular factor, VF) have been shown to have significant effects on the
      capillary basement membrane and on vascular endothelium and they are able to
      stabilise vessel walls. The aim of this study was to assess the effectiveness of
      VF in diabetic patients with non-proliferative DR. Nineteen consecutive patients
      (37 eyes) affected by non-proliferative DR were included in the study and
      randomly assigned to VF or placebo. An ophthalmological examination, colour
      photographies and a retinal fluorescein angiography were carried out before as
      well as 3 and 6 months after inclusion. Every eye in the study was classified in
      accordance with the ETDRS criteria. While the progress of macular oedema and
      visual acuity was very similar in the two groups (VF and placebo), there was no
      deterioration, i.e., no change to a worse classification than that at the start,
      in any of the eyes in the group treated with VF, but deterioration was seen in
      19% of the eyes treated with the placebo. On the basis of these results, VF may
      ensure some protection of the blood-retinal barrier against the harmful influence
      of diabetic microangiopathy.

PMID- 7630624
TI  - Retinal detachment in patients with atopic dermatitis. 5-year retrospective
      survey.
AB  - We surveyed data collected in our department over the past 5 years on all
      patients under the age of 30 years who had presented for repair of retinal
      detachment. Of 52 such patients, 10 (19.2%) had a documented history of atopic
      dermatitis. Three (27.3%) of the 11 eyes (10 patients) with atopic dermatitis
      exhibited a break in the ciliary epithelium in the pars plicata and pars plana,
      the most characteristic finding in this group. Surgical reattachment of the
      retina was accomplished in all 11 eyes. To repair a tear in the ciliary
      epithelium in atopic cases, we prefer using an encircling procedure to
      reconstruct an artificial ora serrata.

PMID- 7630625
TI  - Treatment of postoperative endophthalmitis.
AB  - Despite many advances in microsurgery, asepsis, antibiotics and intraocular
      lenses, postoperative endophthalmitis continues to be responsible for the loss of
      many eyes. In a series of 153 cases of endophthalmitis with a positive culture,
      115 occurred after ophthalmic surgery. Eyes appear to be more vulnerable to this
      complication after extracapsular lens extraction in particular. The analysis of
      the patients operated for cataract in our own department shows that the incidence
      of endophthalmitis is 3 times higher in the extracapsular group with lens
      implantation than in the group of intracapsular lens extraction without lens
      implantation. Quick diagnosis and prompt action are essential to successful
      treatment. The treatment consists of vitrectomy and has the following three
      purposes: (1) provision of a good specimen for direct bacteriological examination
      and culture; (2) removal of toxins and cells, and (3) creation of space for the
      injection of an antibiotic. The authors found highly divergent prognoses and
      bacteriological patterns for endophthalmitis following vitrectomy, bleb surgery
      and cataract. Similar bacteriological agents do not give rise to the same
      prognosis after different operations. The post-lens implantation group (88 cases)
      permitted a distinction to be made between intracapsular and extracapsular
      surgery. A statistically significantly higher percentage of infection by low
      virulence organisms (e.g. Staphylococcus epidermidis) was seen after
      extracapsular surgery: 60% compared to 30%. The analysis shows that this
      difference in bacteriological spectrum is the sole explanation for the better
      functional results following extracapsular surgery.

PMID- 7630626
TI  - Elevated anti-neutrophil cytoplasmic antibody titer in a patient with atypical
      orbital pseudotumor.
AB  - We recently examined a patient with ophthalmic manifestations of Wegener's
      granulomatosis in whom antineutrophil cytoplasmic antibody (cANCA) titers
      provided helpful diagnostic information. A 40-year-old man who had suffered from
      bilateral exophthalmos for 9 months was diagnosed initially as having idiopathic
      inflammatory pseudotumor. The patient exhibited purulent nasal discharge and
      microhematuria. A histopathologic study revealed vasculitis. His ANCA titer for
      cANCA was found to be evaluated, and our patient was subsequently diagnosed as
      having Wegener's granulomatosis. His ocular symptoms resolved and did not recur
      after treatment with corticosteroid in combination with cyclophosphamide. We
      believe that cANCA levels should be investigated in patients with orbital
      pseudotumor as a possible sign of Wegener's granulomatosis.

PMID- 7630627
TI  - B cell differentiation: role of E2A and Pax5/BSAP transcription factors.
AB  - Transcriptional regulation of lineage specific genes has the ability to dictate
      both the proliferative and differentiative potentials of a pluipotent precursor
      cell. The E2A and Pax5/BSAP genes encode transcription factors which bind to B
      cell specific promoters and enhancers and guide the development of immature, but
      committed cells into mature B lymphocytes which express and secrete
      immunoglobulins. In vitro analysis has consistently suggested that these proteins
      regulate distinct classes of genes during B cell differentiation; however, recent
      targeted gene disruption and transgene expression in mice has indicated that
      these genes may actually be components of a single regulatory mechanism which is
      essential for both B lymphocyte differentiation and proliferation.

PMID- 7630628
TI  - Different structural requirements within the switch II region of the Ras protein
      for interactions with specific downstream targets.
AB  - Ras proteins function through the formation of specific complexes with Raf-1, B
      raf, PI-3 kinase and RalGDS. These interactions all require Ras-GTP with an
      intact effector binding domain (Switch I region). We have examined the
      requirements of the Switch II region (amino acids 60-72) for the production of
      stable interactions between Ras and its downstream effectors. A point mutation at
      position 65 or 64 combined with additional mutations at either position 65 or 71
      rendered nucleotide-free Ras protein unable to stably interact with Ras specific
      guanine nucleotide exchange factors. Ha-Ras containing point mutations at
      positions 65 and 71 possessed a twofold higher affinity for B-raf and
      consequently MEK1. The point mutation at 64, in combination with additional point
      mutations at either position 65 or 71, resulted in a protein which failed to
      interact with either PI-3 kinase or neurofibromin, though these Ras mutants
      effectively bound both Raf-1 and B-raf. An activated form of Ras, Q61L-Ras,
      associated with all effector proteins independent of the bound guanine
      nucleotide. Q61L-Ras-GDP was almost as effective as wild type Ras-GMPPNP in the
      in vitro activation of MEK1 and MAP kinase. Competitive studies with the
      catalytic domain if neurofibromin, NF1-GRD, demonstrated that its interaction
      with Ras-GMPPNP is mutually exclusive with both Raf-1 and B-raf. These data
      suggest that rasGAP and neurofibromin are unable to downregulate Ras-GTP
      complexed to Raf-1 or B-raf.

PMID- 7630630
TI  - Adenovirus E1A proteins induce apoptosis by both p53-dependent and p53
      independent mechanisms.
AB  - E1A of human adenovirus type 5 (Ad5) encodes proteins of 289 and 243 residues
      (289R and 243R) which differ only by the 46 amino acid CR3 region known to
      activate expression of certain cellular and early viral genes. E1A proteins also
      induce DNA synthesis and cell transformation, but as well can stimulate
      apoptosis. Two adenovirus E1B products act to protect cells from E1A-induced cell
      death, including a 19 kDa protein which is functionally similar to the cellular
      Bcl-2 suppressor of apoptosis, and a 55 kDa species which binds to and inhibits
      p53. Previous studies suggested that E1A-induced cell death occurs via a p53
      dependent mechanism requiring regions of E1A proteins linked to induction of DNA
      synthesis and cell transformation. We report here that the 289R E1A protein
      induces apoptosis in cell lines lacking p53, whereas the 243R product was
      dependent upon p53. We also show that this p53-independent process involves the
      expression of one or more additional viral proteins which are presumably
      synthesized in response to transactivation by 289R. Thus E1A proteins induce cell
      death by both p53-dependent and p53-independent mechanisms involving separate E1A
      functions.

PMID- 7630629
TI  - Fos proteins can act as negative regulators of cell growth independently of the
      fos transforming pathway.
AB  - The proto-oncogene c-fos is known to be an important positive regulator of cell
      growth and notably of the G0/G1 transition. However, we observed that v-fos or c
      fos-transformed rat-1 fibroblasts paradoxically had a low growth rate as compared
      to control untransformed rat-1 cells. We determined that this slow growth mainly
      reflects an increase of the G1 phase of the cell cycle (up to fourfold). In
      addition, the G0 --> S progression of serum-starved fos-expressing rat-1 cells
      refed with serum was found to be also delayed as compared to rat-1 cells. The
      delayed G0 --> S progression in fos-expressing cells was accompanied by the
      inappropriate levels or kinetics of expression of several cell cycle-regulated
      genes (cyclin D1, cdc2, cdk2, cdk4 and rb). Furthermore, a clear uncoupling of
      the pRb hyperphosphorylation with the entry into S phase was found in these fos
      expressing rat-1 cells. Interestingly, the effect of the Fos proteins on the cell
      cycle was independent of the fos transforming pathway, indicating that the
      effector genes for Fos proteins are likely to be different for each process. In
      conclusion, our results indicate that Fos proteins may act as negative regulators
      of cell growth in some cell types, independently of the fos transforming pathway.

PMID- 7630631
TI  - Progression of carcinoma cells is associated with alterations in chromatin
      structure and factor binding at the E-cadherin promoter in vivo.
AB  - E-cadherin has been identified as a tumor (invasion) suppressor gene, which is
      mutated in 50% of diffuse-type human gastric carcinomas. In other carcinomas, the
      expression of E-cadherin is down-regulated in the poorly differentiated cells
      such as from breast, bladder, lung and colon. We have here examined the in vivo
      properties of the genomic E-cadherin promoter in well and poorly differentiated
      carcinoma cell lines in order to gain insights into the mechanisms of E-cadherin
      down-regulation in tumors. In vivo footprinting analysis revealed that positive
      regulatory elements of the E-cadherin promoter (a GC-rich region, the CCAAT-box
      and a palindromic element) are specifically bound by transcription factors in E
      cadherin-expressing but not in non-expressing cells. The tested cell systems
      include more than a dozen carcinomas cell lines as well as mammary epithelial
      cells where E-cadherin expression can be switched off by activation of a Fos
      estrogen receptor fusion protein and rhabdomyosarcoma cells where E-cadherin
      expression was induced by transfection with E1A. Mapping of DNase I
      hypersensitive sites showed that the chromatin structure in the promoter region
      is loosened in expressing but condensed in non-expressing cells. Furthermore, the
      endogenous E-cadherin promoter is specifically methylated at CpG sites in the
      undifferentiated cells. We also show that the in vivo properties of the promoter
      in E-caherin-negative carcinoma cells are similar as in mesenchymal cells, i.e.
      fibroblasts or sarcoma cells. These data suggest that silencing of the E-cadherin
      promoter during epithelialmesenchymal transition and tumor progression is due to
      a loss of factor binding in vivo and to chromatin rearrangement in the regulatory
      region.

PMID- 7630632
TI  - Increased retinoic acid receptor gamma expression suppresses the malignant
      phenotype and alters the differentiation potential of human neuroblastoma cells.
AB  - Human neuroblastoma (NB) tumor cell lines treated in vitro with the retinoid, all
      trans-retinoic acid (aRA), form neurites and undergo growth arrest. Retinoids
      exert their diverse morphologic effects through a signalling pathway which
      involves the nuclear retinoid receptors. Defective retinoic acid receptor (RAR)
      function contributes to the malignant phenotype of several human and experimental
      tumors. Considerable evidence from gene disruption studies now suggests that one
      of the RARs, RAR gamma, may directly mediate some retinoid effects on embryonic
      and malignant cells. We, firstly, examined primary NB tumor tissue for a
      correlation between endogenous RAR gamma expression and clinical stage of the
      tumor and secondly, the effects of exogenous over-expression of the RAR gamma
      gene on a human NB tumor cell line. RAR gamma mRNA expression in 32 primary NB
      tumor tissue samples were significantly higher in clinically localised tumors
      compared with advanced or disseminated tumors. The human NB tumor cell line,
      BE(2)-C, was stably transfected with a mammalian expression vector (pREP4) over
      expressing the human RAR gamma cDNA. Two selected clones over-expressing RAR
      gamma (BE/G1 and 2) exhibited a reduced growth rate compared to control cells.
      Tumorigenicity was inhibited for BE/G1 cells and there was a delayed onset to
      tumor formation for BE/G2 cells. aRA caused growth inhibition but not neuritic
      differentiation of the BE/G clones, while 9-cis-retinoic acid caused both growth
      arrest and neuritic differentiation. Taken together these results suggest that
      reduced endogenous RAR gamma expression may contribute to the malignant phenotype
      of human NB. In NB cells the retinoid signalling pathway for neuritic
      differentiation may be distinct from that causing growth inhibition.

PMID- 7630633
TI  - p53 independent G0/G1 arrest and apoptosis induced by a novel retinoid in human
      breast cancer cells.
AB  - The biological activity of a novel synthetic retinoid 6-[3-(1-adamantyl)-4
      hydroxyphenyl]-2-naphthalene carboxylic acid (AHPN) was investigated in human
      breast carcinoma (HBC) cells. Although capable of selective binding to the RAR
      gamma nuclear receptor, AHPN inhibited the growth of a number of HBC cell lines
      via RAR- or RXR-independent pathways. AHPN also inhibited the growth of the human
      leukemia cell line HL-60R which does not possess functional RARs. RA
      significantly inhibited AP-1 mediated gene activation in MCF-7 cells while AHPN
      displayed no such anti-AP-1 activity. Retinoids normally are cytostatic in their
      inhibition of breast carcinoma growth and permit cell proliferation upon their
      removal, wher as AHPN induced G0/G1 arrest within 6h followed by apoptosis. In
      MCF-7 cells that harbor wild type p53, AHPN-induced G0/G1 arrest and apoptosis
      was accompanied by p53-independent regulation of WAF1/CIP1 as well as bax mRNA
      levels while bcl-2 mRNA levels were decreased. In MDA-MB-231 cells which possess
      a mutant p53, AHPN-mediated G0/G1 arrest and apoptosis was also associated with a
      concomitant up regulation of WAF1/CIP1 mRNA while these cells did not express bax
      or bcl-2 messages. Thus AHPN represents a novel retinoid that induces G0/G1
      arrest and apoptosis via a unique pathway which appears to involve activation of
      known downstream effectors of p53 in a p53-independent manner.

PMID- 7630634
TI  - Parallel existence of Epstein-Barr virus (EBV) positive and negative cells in a
      sporadic case of Burkitt lymphoma.
AB  - In the Burkitt lymphoma line Oma-BL1, EBV positive and negative cells coexist. We
      demonstrate that EBV positive and negative subclones are identical with respect
      to chromosome markers and HLA type and that the same c-myc rearrangement occurs
      in all the subclones. This shows that the tumor cells are derived from the same
      patient and are of monoclonal origin. In the positive subclones, the EBV genome
      was stably maintained in the episomal form. The EBV negative subclones could be
      derived from previously uncloned tumor cells in early passage, but not from the
      EBV positive subclones.

PMID- 7630635
TI  - Codeletion of p15 and p16 in primary malignant mesothelioma.
AB  - The p15 and p16 CDK4 inhibitor genes map within the chromosome band 9p21 region
      deleted frequently in malignant mesothelioma and other cancers. p16 has been
      implicated recently as a potential target of 9p21 deletions in mesothelioma, but
      the role of this gene is uncertain because deletions have been detected more
      often in established cell lines than in primary tumor specimens. We determined
      p15 and p16 copy number by fluorescence in situ hybridization with a P1 contig in
      50 primary mesotheliomas. Codeletion of p15 and p16 was found in 72% of
      mesotheliomas, including all cases with spindle-cell components (n = 21) and
      total deletion of p15 and p16 was found in several mesotheliomas that lacked
      cytogenetic deletion of the chromosome 9 short arm. Point mutations were not
      found, however, in exon 2 of retained p15 and p16 alleles from seven
      mesotheliomas. These findings demonstrate that p15, p16 and/or a closely
      neighboring gene, are the targets of frequent chromosome 9p deletion in primary
      malignant mesothelioma.

PMID- 7630636
TI  - Motif-primed polymerase chain reaction-based allelotype of sarcomas induced by 3
      methylcholanthrene in interspecific hybrid mice.
AB  - Loss of heterozygosity (LOH) occurs commonly in some human tumors and is thought
      to reflect the selective pressure exerted by tumor suppressor genes. The purpose
      of this study was to examine the genomic location and relative frequency of LOH
      of chemically induced tumors in an established mouse model for chemical
      carcinogenesis. Twenty-four tumors were induced by subcutaneous injection of 3
      methylcholanthrene into inter-subspecific hybrid (C57BL/6J x SPRET/Ei)F1 mice.
      Tumors were diagnosed as poorly differentiated, spindle cell sarcomas. DNA
      isolated from cell cultures derived from the sarcomas was analysed for LOH using
      a multi-locus genome scanning technique, motif-primed PCR, followed by
      conventional simple sequence length polymorphism (SSLP) PCR markers. Ninety-one
      motif-primed PCR products and seven SSLP markers were evaluated, covering
      segments of 39 out of 41 chromosomes. LOH was extremely rare; average fractional
      allelic loss per tumor was less than 0.01 suggesting a remarkable genetic
      stability of the tumors and that genetic events leading to transformation are
      only rarely revealed as LOH. However, some regions exhibiting LOH were identified
      encompassing both known and hypothesized tumor suppressor loci such as Trp53.
      These data indicate that motif-primed PCR is an efficient method of scanning the
      genome of interspecific sarcomas for rare mutational events generating LOH during
      tumor induction. Cell lines derived from the sarcomas promise to be useful for
      identifying genes whose inactivation causes increased malignancy during tumor
      progression.

PMID- 7630637
TI  - Induction of B cell lymphomas by overexpression of a Myb oncogene truncated at
      either terminus.
AB  - The c-myb oncogene encodes a nuclear transcriptional transactivator that is often
      terminally truncated in hematopoietic tumors. To directly assess the tumorigenic
      activity of full length and terminally-truncated variants of c-myb, we have
      overexpressed several structurally-altered forms of myb within an avian
      retroviral vector and have shown that overexpression of truncated (but not full
      length) myb transforms both myeloid cells in vitro and mesenchymal cells in vivo.
      In vivo infection with these truncated myb viruses is now shown to induce
      metastatic B cell lymphomas in a significant minority of animals. Evaluation of
      the lymphomas revealed two distinct mechanisms of myb-induced tumorigenesis. In
      most of the lymphomas, proviral DNA inserted into the endogenous chicken c-myb
      gene and promoted the expression of a 5'-truncated myb transcript encoding an
      amino terminal truncated protein. In comparison, some animals infected with a
      virus encoding a carboxyl (C) terminal truncated myb (T-myb) developed non
      insertional B cell lymphomas that directly expressed the provirally-encoded T-myb
      gene. The lymphomagenic T-myb protein lacks 214 C terminal amino acids including
      all of the myb transcription inhibition domain. This novel lymphomagenic activity
      for a C terminal truncated myb suggests that a loss of regulatory sequences at
      either end of c-myb is sufficient to create a B cell-specific transforming gene.

PMID- 7630638
TI  - Transcription factor IRF-2 exerts its oncogenic phenotype through the DNA
      binding/transcription repression domain.
AB  - The Interferon Regulatory Factors-1 and -2 (IRF-1 and IRF-2) play a
      transcriptional role in the regulation of the IFN-beta gene as well as other
      immunoregulatory genes. IRF-1 serves as a transcriptional activator whereas IRF-2
      acts as an antagonistic transcriptional repressor. IRF-1 and IRF-2 also play
      opposing functional roles in cell growth regulation, and are implicated as a
      potential antioncogene and oncogene, respectively. To analyse the relationship
      between DNA binding/transcriptional repression and oncogenic transformation,
      NIH3T3 cells expressing C-terminal deletions of IRF-2 were established and
      assayed for transformation by saturation density analysis, anchorage independent
      growth in soft agar and tumor formation in nude mice. Cells expressing an IRF-2
      protein of at least 160 N-terminal amino acids were transformed in vitro and
      tumorigenic in vivo, thus mapping IRF-2 oncogenic activity to its DNA
      binding/transcriptional repression domain. Overexpression of wild-type and
      truncated IRF-2 proteins resulted in reduced IFN-beta mRNA levels following
      induction by dsRNA. However, there was no effect of IRF-2 on IFN-beta
      inducibility by Sendai virus infection, suggesting the involvement of multiple
      IFN-beta induction pathways. In DNA binding assays, recombinant IRF-2 was found
      to preferentially bind to the IFN-beta PRDI site compared to IRF-1. These studies
      indicate that the transformed phenotype resulting from overexpression of IRF-2
      may be due to constitutive engagement of the IRF-E recognition site, thus
      preventing DNA binding and transactivation of putative tumor suppressor genes by
      the IRF-1 anti-oncogene.

PMID- 7630640
TI  - Determination of sequences responsible for the differential regulation of Myc
      function by delta Max and Max.
AB  - The DNA-binding, transcriptional activation and transforming activities of the
      Myc protein require dimerization with Max. Max can form also homodimers which are
      able to bind the same DNA sequence as Myc/Max heterodimers and suppress Myc
      induced transcription and transformation. We have recently identified a naturally
      occurring truncated form of Max, delta Max, which in a rat embryo fibroblast
      enhances transformation by Myc and Ras. Like Max, this delta Max protein contains
      a b-HLH-Zip domain, except that the end of the leucine zipper is replaced by five
      delta Max-specific amino acid residues. Delta Max also lacks the C-terminal
      sequences of Max including a nuclear localisation signal. Here we have dissected
      the regions responsible for the specific effects of Max and delta Max in Ras-Myc
      cotransformation of rat embryo fibroblasts. Our results indicate that the
      suppressive activity of Max requires C-terminal acidic and basic regions and an
      intact leucine zipper. Replacement of the end of the leucine zipper with the
      delta Max-specific sequence is responsible for the enhancement of transformation
      by delta Max. Surprisingly, delta Max does not require the DNA-binding basic
      region for enhancement of transformation and has no effect on Myc-induced
      transcription activation from Myc/Max-binding site-containing promoter construct.

PMID- 7630639
TI  - The alveolar rhabdomyosarcoma PAX3/FKHR fusion protein is a transcriptional
      activator.
AB  - Chimeric transcription factors, created by gene fusions as the result of
      chromosomal translocations, have been implicated in the pathogenesis of several
      pathologically disparate solid tumors. The PAX3/FKHR fusion gene, formed by a
      t(2;13)(q35;q14) in alveolar rhabdomyosarcoma, encodes a hybrid protein that
      contains both PAX3 DNA binding domains, the paired box and homeodomain, linked to
      the bisected DNA binding domain of FKHR, a member of the forkhead family of
      transcription factors. Here we report that PAX3 and PAX3/FKHR display similar,
      but not identical transactivation activities when tested with model Pax
      recognition sequences. No functional role could be ascribed solely to the
      residual FKHR binding domain present in the fusion protein, but FKHR was found to
      contribute a strong carboxyl terminal activation domain replacing the one located
      in the unrearranged PAX3 gene. We show that the native PAX3/FKHR protein present
      in tumor cells with this translocation has transcriptional characteristics
      similar to the in vitro expressed protein. The ability of the PAX3/FKHR hybrid
      protein to bind DNA in a sequence specific manner and to transactivate the
      expression of artificial reporter genes suggests that its aberrant expression
      could subvert the transcriptional programs that normally control the growth,
      differentiation, and survival of primitive myogenic precursors in vivo.

PMID- 7630641
TI  - Antisense to cyclin D1 inhibits growth and reverses the transformed phenotype of
      human esophageal cancer cells.
AB  - The cyclin D1 gene is amplified and overexpressed in a significant fraction of
      human esophageal tumors, and several other types of human cancer, but the
      functional significance of this overexpression has not been established. To
      further address the roles of cyclin D1 in growth control and tumorigenesis, we
      have overexpressed an antisense cyclin D1 cDNA construct, either constitutively
      or inducibly, in the HCE7 human esophageal cancer cell line in which cyclin D1 is
      amplified and expressed at high levels. The expression of antisense cyclin D1 led
      to decreased expression of cyclin D1 at both mRNA and protein levels, and this
      was associated with a marked inhibition of cell proliferation. Antisense cyclin
      D1 expressing cells displayed a decreased plating efficiency, increased doubling
      time, decreased saturation density, increased cell size, decreased cyclin D1
      associated in vitro kinase activity, decreased anchorage-independent growth, and
      a loss of tumorigenicity in nude mice. These findings provide direct evidence
      that the overexpression of cyclin D1 in certain tumor cells contributes to their
      abnormal growth and tumorigenicity. The ability to revert the transformed
      phenotype of these cells with antisense cyclin D1 suggests that cyclin D1 may be
      a useful target in cancer therapy.

PMID- 7630642
TI  - Loss of heterozygosity at 9p23 defines a novel locus in non-small cell lung
      cancer.
AB  - Genetic studies have previously demonstrated cytogenetic deletions and allelic
      imbalance or loss of heterozygosity (LOH) on the p arm of chromosome 9, in a
      number of tumour types. We have analysed 45 Non-Small Cell Lung Cancers (NSCLC)
      with a panel of highly polymorphic microsatellite markers on chromosome 9. Our
      results indicate that loss on 9p is concentrated within the D9S156-D9S161 region
      with 44% (20/45) LOH, however the area with minimal loss in this set of lung
      tumours was found at D9S157 (9p23), with 30% LOH (10/33), whereas loss at the
      IFNA locus was only found in 6% (2/34) tumours. Five of the lung tumours in this
      study which demonstrated LOH at D9S157 retained heterozygosity at the adjacent
      informative markers lying centromeric and telomeric to D9S157. No correlations
      were found between any of the clinico-pathological parameters and LOH on 9p or at
      the D9S157 locus. The results of this study indicates the presence of a further
      putative tumour suppressor gene on 9p at the D9S157 locus (9p23) to be most
      likely involved in the pathogenesis of non-small cell lung cancer.

PMID- 7630643
TI  - Differential effects by Mad and Max on transformation by cellular and viral
      oncoproteins.
AB  - c-Myc is an essential component of the regulatory mechanisms controlling cell
      growth. Max is the obligatory partner of c-Myc for all its biological functions
      analysed to date. Recently two Max interacting proteins, Mad and Mxi1, have been
      identified. It has been suggested that these two proteins modulate c-Myc
      function, in the simplest model by competing with c-Myc for the interaction with
      Max. We have analysed different aspects of Mad function in comparison to Max.
      Native Mad/Max heterodimers bound specifically to a c-Myc/Max consensus DNA
      binding site. Furthermore Mad inhibited efficiently c-Myc, mutant p53, adenovirus
      E1a, or human papilloma virus type 16 transformation of rat embryo cells in
      cooperation with activated Ha-Ras. Myc transformed clones showed an increased
      cell cycle time and a reduced immortalization frequency after cotransfection with
      either mad or max. In contrast to Mad, Max did not inhibit E1a/Ha-Ras
      cotransformation but repressed c-Myc/Ha-Ras transformation efficiently. Mad delta
      N, an N-terminal deletion mutant of Mad, was as efficient in repressing c-Myc/Ha
      Ras cotransformation as full length Mad but showed little inhibitory activity
      when assayed on E1a/Ha-Ras. Unlike wt Mad, Mad delta N had little effect on cell
      growth. Our data suggest that Mad affects cell growth at least in part by a c-Myc
      independent mechanism.

PMID- 7630644
TI  - Frequent loss of heterozygosity on chromosome 9, and low incidence of mutations
      of cyclin-dependent kinase inhibitors p15 (MTS2) and p16 (MTS1) genes in gliomas.
AB  - Four cyclin-dependent kinase inhibitors called p15, p16, p21 and p27 have been
      identified in mammals. Because these proteins participate in the control of cell
      cycle, they are potential targets for somatic mutations during carcinogenesis. In
      order to document the prevalence of p15 and p16 alterations in gliomas, we looked
      for loss of heterozygosity of chromosome 9p where these genes are localized.
      Allelic losses were observed in 31 of 44 investigated cases. In all cases they
      involved the p15/p16 locus. We then looked for mutations in the p16 and p15 genes
      in 46 gliomas. A total of three DNA variants were observed which were all present
      in the matched constitutional DNA. They may be unrelated to tumor development. A
      single somatic mutation was detected. It involved a C to G substitution in codon
      93 of p16 and is predicted to change a threonine into an arginine. Taken
      together, these data indicate that inactivation by point mutation of these two
      cyclin-dependent kinase inhibitors is uncommon in glial tumor carcinogenesis, but
      that there may be a tumor suppressor gene on 9p in the vicinity of p16 and p15
      genes.

PMID- 7630645
TI  - Pattern of ras and gsp oncogene mutations in radiation-associated human thyroid
      tumors.
AB  - The preferential activation of the Ki-ras oncogene in follicular radiation
      associated human thyroid carcinomas, has been suggested by Wright et al. (1991).
      However, only 12 thyroid tumors were analysed in this study. In order to confirm
      if radiation favours, in human thyroid tumorigenesis, the appearance of a
      particular molecular lesion, we studied 33 benign and malignant human radiation
      associated thyroid tumors. We used polymerase chain reaction (PCR) amplification
      and allele-specific hybridization with mutant-specific probes for the three ras
      genes and the gsp oncogene. Compared to 85 'spontaneous' human thyroid tumors,
      the radiation-associated cases: (1) show a similar overall frequency of ras and
      gsp mutations (about 30% and 6% respectively); (2) present a similar frequency of
      mutation of the three ras genes without any predominance in adenomas and
      papillary carcinomas and (3) all Ki-ras mutations were found in papillary
      carcinomas (4/15). ras and gsp genes were never found mutated simultaneously,
      suggesting an alternative role for both oncogenes in the thyroid tumorigenic
      radiation-associated process.

PMID- 7630646
TI  - Is there a central pattern generator in man?

PMID- 7630647
TI  - Mean term follow-up of a series of post-traumatic syringomyelia patients after
      syringo-peritoneal shunting.
AB  - We report the follow-up of a series of post-traumatic syringomyelia patients
      treated by syringo-peritoneal shunting (SPS). The neurological status was
      determined following the international ASIA/IMSOP standards for neurological
      classification of spinal cord injury; this was completed by a modified
      Silberstein classification that identifies the ascending neurological symptoms as
      well as the increasing myelopathic symptoms in patients with post-traumatic
      syringomyelia. Magnetic resonance imaging (MRI) was systematically performed to
      assess the presence of a postoperative residual syrinx or of meningeal fibrosis.
      Eight patients were studied (five men, three women) with an age ranging from 17
      to 54 years (mean of 30.7 years) at the time of the spinal cord injury. Three had
      a complete or nearly complete paraplegia, five were incomplete. The post
      traumatic syringomyelia was diagnosed from 2 to 8 years after the spinal cord
      injury and was treated by syringo-peritoneal shunting. Early complications
      occurred in three patients: (1) displacement of the catheter, (2) obstruction of
      the catheter, and (3) haematomyelia, which disappeared after a new surgical
      procedure was performed. The postoperative follow-up ranged from 3 to 9 years
      (mean of 4.5 years). The neurological level decreased in every case and the
      ascending neurological symptoms decreased or were stabilised in seven patients.
      The postoperative ASIA/IMSOP scores and the increasing myelopathic symptoms
      improved in four patients but worsened in the four others, incomplete. The MRI
      showed an important decrease of the syrinxes in every patient associated with a
      serious meningeal fibrosis in five cases. Syringo-peritoneal shunting seems to be
      efficient in the treatment of the syrinx but may have a poor effect regarding the
      prevention of meningeal fibrosis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7630648
TI  - Prevention of spinal injuries from diving in Slovenia.
AB  - Injury of the cervical spine involving the spinal cord such as results from
      diving into shallow water causes very severe disability. In spite of progress in
      medical science, results of the treatment and rehabilitation of such patients are
      not satisfactory. Every effort should be undertaken to give young swimmers, the
      most frequent victims of diving injuries, proper instructions to prevent spinal
      cord injury. A broadly conceived national prevention programme, developed under
      the catch-phrase 'Do Not Jump into the Unknown', has been under way in Slovenia
      during the past 3 years, and has been promoted in collaboration with the Health
      Protection Institute of Slovenia. In these years the number of new spinal cord
      injuries decreased (one-two per year), but it is too early to conclude that this
      is the result of the prevention activities. But it is obvious that knowledge of
      this type of injury is now much more widespread.

PMID- 7630649
TI  - Experimental spinal cord transplantation as a mechanism of spinal cord
      regeneration.

PMID- 7630650
TI  - Neurological recovery, mortality and length of stay after acute spinal cord
      injury associated with changes in management.
AB  - Based on epidemiological data from two populations of patients with acute spinal
      cord injury (ASCI), three outcome measures were compared to evaluate the
      effectiveness of management of ASCI patients in a regional, specialized acute
      spinal cord injury unit (ASCIU). The two populations consisted of a pre-ASCIU
      group of 351 patients managed from 1947-73 before the establishment of the ASCIU,
      and an ASCIU group of 201 patients managed in an ASCIU from 1974-81. The three
      outcome measures were mortality rate, length of stay (LOS) during first
      hospitalization, and neurological recovery. Linear regression and multiple
      regression analyses were used to determine whether differences in the outcome
      measures were attributable to differences in admission variables in addition to
      the influence of the ASCIU. The results showed that the patients treated in the
      ASCIU had a significant reduction in the mortality rate of almost 50% (P =
      0.022), a significant reduction in the LOS of almost 50% (P < 0.001), and a
      significant increase in neurological recovery consisting of a doubling of the
      neurological recovery scale utilized (P < 0.001). Multiple regression analysis
      showed that the reduction in mortality rate was significantly influenced by
      differences in the admission variables between the two groups. However, the
      establishment of the ASCIU was associated with a significant reduction in LOS and
      a significant improvement in neurological recovery. Thus, these results support
      the view that management of ASCI patients in a regional, multidisciplinary unit
      is medically advantageous and can reduce the LOS.

PMID- 7630651
TI  - The influence of bladder management on fertility in spinal cord injured males.
AB  - Male infertility is a well recognised problem following spinal cord injury. The
      techniques of vibration induced ejaculation and transrectal electroejaculation
      have significantly increased the likelihood of sperm retrieval in spinal cord
      injured males; however, the reproductive capacity remains markedly reduced due to
      poor semen quality. The Spinal Injuries Unit at Royal North Shore Hospital has
      developed a programme to achieve seminal emission and enhance fertility. This
      study analysed the results of the first sample obtained at stimulation in 70
      spinal cord injured males with respect to procedure performed, neurological
      level, completeness of lesion, bladder management, infection, age and duration
      since injury. Our study demonstrated that bladder management and neurological
      level were significant factors affecting the presence of motile sperm.
      Individuals managing their neuropathic bladder by catheter (intermittent self
      catheterisation, indwelling urethral or suprapubic catheter) had significantly
      enhanced semen quality compared to those voiding by reflex or straining.
      Differences were also noted within the catheter group itself with intermittent
      self-catheterisation achieving a higher percentage of motile sperm present.

PMID- 7630652
TI  - Maximal physiological responses during arm cranking and treadmill wheelchair
      propulsion in T4-T6 paraplegic men.
AB  - The aim of the study was to compare the exercise responses during maximum
      wheelchair propulsion on a motor driven treadmill (TM) and maximum arm cranking
      (AC) in a homogenous group of nine paraplegic men with clinically complete spinal
      cord lesions between T4 and T6. The test order for each ergometer was random and
      time between the two ergometer tests was 3-7 days. All experiments were conducted
      in an air conditioned environment (23 degrees C DB, 18 degrees C WB). The highest
      VO2 recorded during the final minute of arm cranking (1.65 +/- 0.14 l min-1) and
      wheelchair propulsion on the treadmill (1.72 +/- 0.10 l min-1) was not
      significantly different. There were no significant differences in heart rate
      during the final minute of arm cranking (177 +/- 3 b min-1), and wheelchair
      propulsion on a motor driven treadmill (177 +/- 4 b min-1), nor were there any
      significant differences in minute ventilation (STPD) between AC (52 +/- 6.6 l min
      1) and TM (56.1 +/- 4.8 l min-1). The VCO2 l min-1 for AC (2.00 +/- 0.20 l min-1)
      and TM (2.00 +/- 0.12 l min-1) was also not significantly different. The present
      study found that, unlike previous studies, no significant differences in VO2 (l
      min-1, ml kg-1 min-1) VE (l min-1), VCO2 (l min-1) or heart rate (b min-1) were
      found between the two modes of ergometry during the last minute of incremental
      exercise to exhaustion in a homogenous group of T4-T6 paraplegic men.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7630653
TI  - Treatment of sleep apnoea in spinal cord injured patients.
AB  - Little is known about sleep disorders in spinal cord injured (SCI) patients.
      Three SCI patients who reported severe daytime sleepiness and sleep complaints
      were evaluated with nocturnal polysomnography and oxygen saturation with
      pulsoximeter on several occasions at home. In addition respiratory registration
      was preformed during overnight stay in the hospital. Two patients who had sleep
      apnoea episodes with reduced oxygen saturation during sleep were treated with
      continuous positive airway pressure with good results on sleep architecture,
      oxygen saturation, and daytime sleepiness. One obese patient was advised to lose
      weight and to reduce smoking and alcohol consumption, and following this advice
      his sleep related problems were reduced with no further treatment necessary. It
      is suggested that SCI patients who complain about sleep related disorders should
      be appropriately screened, with inclusion of nocturnal polysomnography, oxygen
      saturation, and respiratory registration and, depending on the screening results,
      appropriate advice/treatment applied.

PMID- 7630654
TI  - Bronchodilatory effects of ipratropium bromide in patients with tetraplegia.
AB  - Airway hyperresponsiveness was recently described in patients with chronic
      cervical spinal cord injury (tetraplegia). The response was attributed to
      unopposed cholinergic broncho-constrictor activity due to loss of sympathetic
      innervation of the airway. To determine if the administration of a cholinergic
      antagonist alters resting airway tone in these patients, ipratropium bromide (72
      micrograms) was administered by aerosol to 25 tetraplegic patients. We found that
      12 of 25 patients (48%) had significant improvement (defined as > or = 12%) in
      forced expired volume in 1 s (FEV1) and/or forced vital capacity (FVC). A
      significant correlation between airway responsiveness and complaints of dyspnea
      at rest, completeness of injury (sensory), or smoking history was not found.
      These findings of improved airflow after the use of an anticholinergic
      bronchodilator agent provides further evidence that transection of the cervical
      cord results in unopposed parasympathetic activity and a resultant increase in
      resting airway tone.

PMID- 7630655
TI  - Supraventricular tachycardia as a presenting sign of pulmonary embolism in
      paraplegia. Case report and review.
AB  - Pulmonary embolism is a major complication after spinal cord injury and difficult
      to diagnose in any patient. Supraventricular tachycardia (SVT) is an unusual
      presentation for pulmonary embolism (PE). This article documents the records of a
      60-year-old patient who was undergoing comprehensive rehabilitation after
      traumatic spinal cord injury and multitrauma. His treatment programme was
      interrupted by a PE with SVT as the only presenting symptom. This article
      outlines the clinical approach to the diagnosis of pulmonary embolism. A high
      index of suspicion of PE should always be kept in mind when SVT occurs in a
      spinal cord injured patient.

PMID- 7630656
TI  - Osteoporotic vertebral collapse with late neurological complications.
AB  - This paper describes 27 patients who had a spinal fracture and underwent an
      anterior or a posterior spinal decompression, with or without spinal
      instrumentation, for late neurological compromise secondary to post-traumatic
      vertebral collapse associated with osteoporosis. Five males and 22 females were
      studied, with an average follow-up of 3.7 years. The patients developed delayed
      neurological compromise due to osteoporotic vertebral collapse 1 month to 1.5
      years following insignificant spinal fractures. Abnormal hypermobility at the
      collapsed spinal level with gradual retropulsion of fracture fragments into the
      spinal canal appeared to contribute to late paralysis. This pathology is treated
      surgically either anteriorly or posteriorly, but we recommend transpedicular
      posterolateral decompression and stabilization with a screw-rod construct because
      of technical ease and minimum invasion.

PMID- 7630657
TI  - Development of the Wheelchair User's Shoulder Pain Index (WUSPI).
AB  - Chronic shoulder pain is a frequently reported phenomenon in individuals who use
      wheelchairs as their primary means of mobility. No indices are currently
      available which detect difficulties in performing daily activities due to
      shoulder discomfort in a largely independent population of wheelchair users. The
      Wheelchair User's Shoulder Pain Index (WUSPI) was designed to measure shoulder
      pain in individuals who use wheelchairs. A pilot index was created to measure
      shoulder pain and related difficulty during basic and instrumental activities of
      daily living. The instrument was administered to 64 wheelchair users at an
      athletic event. Analyses of internal consistency and interitem correlations were
      used to revise and refine the original instrument. Individual item analysis
      revealed that the subjects in this study experienced the most shoulder pain when
      wheeling up an incline or on outdoor surfaces, when lifting an object from an
      overhead shelf, when trying to sleep, when transferring from tub to wheelchair
      and when washing their backs. The final 15-item index shows high internal
      consistency. This instrument is useful for both clinical and research purposes to
      detect and monitor shoulder pain and accompanying loss of function by wheelchair
      users.

PMID- 7630658
TI  - Spinal brucellosis: a personal experience of nine patients and a review of the
      literature.
AB  - A retrospective study of patients with spinal brucellosis was performed to
      outline the syndrome and its treatment, including rehabilitation. The patients
      were admitted to our spinal cord unit between 1975 and 1990. We studied nine
      patients (five males and four females), with a mean age of 49 years, and not
      belonging to any professional risk group except for one patient. At discharge,
      there was an improvement in sphincter control, execution of daily living
      activities and walking ability. No improvement was found in the neurological
      status. In conclusion we emphasize the importance of the prevention, early
      diagnosis and adequate treatment of the condition to minimise the neurological
      sequelae.

PMID- 7630659
TI  - Sports injuries in athletes with disabilities: wheelchair racing.
AB  - This study investigates the incidence of sports injuries in athletes who
      participate in wheelchair racing in the UK. Wheelchair racing has been identified
      as one of the top 'injury risk' sports but little information is available as to
      the incidence or type of injury sustained by British athletes. A questionnaire
      was used to collect information about injuries sustained in the last 12 months.
      Members of the British Wheelchair Racing Association (BWRA) were sent
      questionnaires. Most subjects (72%) reported having at least one injury within
      the previous 12 months. Training variables such as the distance pushed per week
      (Mann-Whitney U = 61, P > 0.05), the amount of speed training (Mann-Whitney U =
      110, P > 0.05), the number of weight training sessions (Mann-Whitney U = 26, P >
      0.05) or the length of time the athlete had been involved in wheelchair racing
      (Mann-Whitney U = 103, P > 0.05) were not associated with the occurrence of an
      injury. Overuse injuries were common and recurred more often than other types of
      injuries (chi 2 = 3.95, P < 0.05). Those athletes with recurring injuries also
      tended to be those who restarted training before they were pain-free from their
      injury (chi 2 = 5.31, P < 0.05). There appears to be a link between overuse
      injuries, the presence of pain during training and the recurrence of injuries. A
      lack of knowledge about sports injuries, what causes them and what to do
      following an injury may contribute to the high incidence of overuse injuries in
      this group of athletes.

PMID- 7630660
TI  - Acute hypotension associated with terbutaline nebuliser therapy in a traumatic
      tetraplegic patient during the spinal shock phase. Case report.
AB  - Acute hypotension was observed during the spinal shock stage of a 35-year-old C3
      complete tetraplegic patient after receiving nebulised terbutaline for
      respiratory therapy. Nine weeks later, when he had recovered from spinal shock,
      he again received nebulised terbutaline but there was no significant fall in
      arterial blood pressure. This case illustrates the possibility of a serious
      degree of hypotension occurring in such patients with this drug.

PMID- 7630661
TI  - Autonomic dysreflexia--don't let it be a surprise.
AB  - This article discusses autonomic dysreflexia, which can occur in patients with
      spinal cord injury. This potentially life-threatening complication can be managed
      through an understanding of the disorder and its primary causes. The primary
      cause of this problem is usually a noxious stimuli that precipitates an abnormal
      response from the autonomic nervous system. Prevention is the primary nursing
      treatment and includes implementation of a bladder and bowel management program
      early in the treatment of the patient with spinal cord injury.

PMID- 7630662
TI  - Addressing issues of sexuality with spinal cord injured persons.
AB  - For many years society viewed the spinal cord injured person as an asexual being.
      Within the past 10 years health care providers have recognized the need to
      incorporate information sexuality into the care of this population. This article
      reviews the physiologic and psychologic changes experienced by the spinal cord
      injured person, explores methods of enhancing the physiologic function inherent
      in the sexual experience, and presents nursing's role in sexual counseling.

PMID- 7630663
TI  - Tape injury in the patient with total hip replacement.
AB  - Patients undergoing total hip replacement surgery may experience edema around the
      incision related to intraoperative positioning and manipulation of the extremity,
      as well as general soft tissue damage. The edema may contribute to the impairment
      of skin integrity when tape is applied to secure postoperative dressings. This
      article describes how the problem of impaired skin integrity was identified and
      the process used to determine the contributing factors. The interventions used by
      three nursing specialty areas to correct the problem are also described.

PMID- 7630664
TI  - Chest pain: developing rapid assessment skills.
AB  - Chest pain is a common complaint among adult patients. Chest pain may be a signal
      of an impending life-threatening event. The accurate assessment of chest pain is
      difficult. The responsibility of identifying a potentially life-threatening
      condition accompanied by chest pain presents the nurse with an incredible
      challenge. Chest pain may be caused by a variety of cardiac, respiratory,
      gastrointestinal and musculoskeletal illnesses. A complete, thorough history that
      includes family history and risk factors is the most important part of the
      assessment. The history is followed by the physical assessment. This phase of the
      assessment process may include important tests such as a chest X-ray, 12-lead
      electrocardiograph and cardiac isoenzymes. A perceptive and observant nurse with
      astute assessment skills will set the tone for optimal patient treatment leading
      to a more positive outcome for the patient.

PMID- 7630665
TI  - The first 3 minutes: code preparation for the staff nurse.
AB  - Nurses who care for a range of medical-surgical patients may not be required to
      have ACLS training and may have limited experience in dealing with cardiac or
      pulmonary arrest. A need for staff training was identified by the designated code
      team members with the critical focus being the first 3 minutes of the code. A
      code preparation class was developed reflecting the staff's areas of deficiency.
      After all medical-surgical units had attended the class, mock codes were
      initiated, focusing on skills required of licensed nurses or nursing assistants
      before the arrival of the code team. This code preparation program resulted in
      staff nurses becoming more skilled and comfortable with their roles during a
      cardiopulmonary arrest.

PMID- 7630666
TI  - The "turn-up" plasty: one solution to a complex problem.
AB  - This case study presents a patient with severe osteomyelitis of the femur, which
      did not respond to vigorous antibiotic therapy. Compromised kidney function,
      malnutrition, and copious drainage from an open wound led the patient and
      physician to select a seldom used procedure, the "turn up" plasty to treat the
      problem. This procedure provides a stump for an above-the-knee prosthesis
      providing the patient with more optimal function than if the femur and lower leg
      were amputated. The procedure involves removal of the infected femur, foot
      amputation, knee disarticulation and turning the lower leg up, using the tibia to
      support the femoral component of a joint replacement. After several months, the
      patient is wearing a prosthesis, walking without pain, and satisfied with his
      decision.

PMID- 7630667
TI  - Attributes of mentors as perceived by orthopaedic nurses.
AB  - Mentoring in nursing is a concept that merits close scrutiny in today's chaotic
      health care environment. Mentors can shape a positive environment for nurses to
      nurture career development, satisfaction and leadership. One of the issues of
      mentoring is that there is no agreement as to the role and functions of a mentor.
      Most of the controversy deals with the similarities and differences between
      mentors and preceptors. The purposes of this study were to identify attributes of
      mentors as perceived by orthopaedic nurses and to identify who orthopaedic nurses
      feel are the most appropriate persons to serve as mentors. This may enable
      nursing leaders to develop specific programs and strategies to increase job
      satisfaction and nurse retention among orthopaedic nurses.

PMID- 7630668
TI  - From the president: diversity.

PMID- 7630669
TI  - Communicating with your legislator--You can and you should.

PMID- 7630670
TI  - Rehabilitation of the spinal cord injured patient.
AB  - Spinal cord injury affects about 200,000 people in the United States. This
      article discusses the disease process after acute hospitalization and the role of
      the nurse in the care and empowerment of the spinal cord injured patient during
      the rehabilitation phase. In addition to a review of didactic information
      concerning spinal cord injuries, this article will focus on the role of the nurse
      as "teacher." The manuscript stresses the importance of patient involvement and
      that the ultimate goal of successful rehabilitation (a lifelong process) is for
      the patient to direct and plan his or her own care.

PMID- 7630672
TI  - Antibody response of low birth weight infants to Haemophilus influenzae type b
      polyribosylribitol phosphate-outer membrane protein conjugate vaccine.
AB  - OBJECTIVE: To evaluate the effectiveness in low birth weight (LBW) infants of the
      currently recommended immunization schedule for conjugated Haemophilus influenzae
      type b (HIB) vaccine. METHODS: We quantified antibody responses in 36 preterm
      infants with a mean birth weight of 1060 g and a mean gestational age of 28
      weeks. Infants were immunized with 0.5 mL of HIB vaccine at 2 and 4 months'
      postnatal age. Specific HIB antibodies were quantified on cord blood, immediately
      before each immunization and 2 months after the last immunization. RESULTS: Even
      though the geometric mean titers increased significantly during the study period,
      they were still markedly lower than values reported in term infants. After the
      second immunization, only 24 infants (67%) attained antibody concentrations of
      more than 0.25 micrograms/mL, defined as seropositivity. Also, only 53% of
      infants achieved antibody concentrations of more than 1.0 micrograms/mL compared
      with 92% as reported in term infants. Stepwise logistic regression identified
      gestational age of 27 weeks or less and the amount of intravenous immunoglobulin
      received as the significant variables influencing the antibody response after the
      first immunization. The incidence of side effects was negligible. CONCLUSIONS: We
      conclude that LBW infants, and especially those born at 27 or less weeks'
      gestation, do not respond as effectively to the HIB vaccine. We speculate that
      reevaluation of the current immunization schedule may be required for very LBW
      infants.

PMID- 7630673
TI  - Use of dexamethasone in the outpatient management of acute laryngotracheitis.
AB  - OBJECTIVE: Recent studies have demonstrated that a single intramuscular injection
      of dexamethasone (0.6 mg/kg) shortens the duration and severity of illness in
      hospitalized patients with acute viral laryngotracheitis (croup). Our objective
      was to determine if dexamethasone has a role in the outpatient management of
      patients with acute viral croup of moderate severity. METHODS: Patients, 6 months
      to 5 years of age, who came to the emergency department (ED) with acute viral
      croup, a croup score of at least 2 (range 0 to 17), and a disposition of
      discharge were randomized in a double-blind fashion to receive a single
      intramuscular injection of dexamethasone, 0.6 mg/kg, or an equal volume of normal
      saline before discharge from the ED. Patients were excluded if they had any
      structural abnormalities, had received any steroids in the preceding 24 hours, or
      if they required beta-agonist therapy, more than one racemic epinephrine
      treatment, or hospitalization. Patients were followed up by telephone 24 hours
      and 7 to 10 days after discharge to determine whether additional medical
      attention was sought for perceived lack of improvement or worsening of symptoms.
      Secondary outcome included the parents' perception of how the child was doing at
      24 hours, based on a 4-point ordinal scale: worse (1), same (2), improved (3),
      symptoms resolved (4), and the number of days it took for complete recovery.
      RESULTS: Of the 38 patients comprising the study group, 19 received
      dexamethasone. The median age was 19 months (range 6 to 66 months), and median
      pretreatment croup score was 3 (range 2 to 5) for both groups. The number of
      patients requiring racemic epinephrine was similar in both groups. Five patients
      sought additional medical attention within 48 hours. Four of the five patients
      had received placebo (21% of the placebo group) and one had received
      dexamethasone (5% of the steroid group) (not statistically significant). At the
      24-hour telephone follow-up, significantly more patients in the dexamethasone
      group had a score consistent with improvement compared with placebo (84% vs 42%,
      P = .003). There was no difference in the number of days for symptoms to
      completely resolve between the two groups. CONCLUSION: The use of dexamethasone
      in the outpatient management of viral croup was associated with a reduction in
      severity of illness within 24 hours after treatment. Patients with viral croup of
      moderate severity should be considered as candidates for the use of dexamethasone
      before discharge from the ED.

PMID- 7630671
TI  - Helicobacter pylori infection in recurrent abdominal pain in childhood:
      comparison of diagnostic tests and therapy.
AB  - OBJECTIVE: To determine the role of Helicobacter pylori infection in children
      with recurrent abdominal pain and the usefulness of serologic tests in screening
      H pylori infection and monitoring treatment of H pylori-associated gastritis.
      METHODS: During a 3 year period, we investigated the presence of serum
      immunoglobulin G (IgG) antibody to H pylori in 456 children using the high
      molecular-weight cell-associated protein H pylori enzyme immunoassay kit. Among
      the 456 children studied, 218 (age range, 3 to 18 years; mean age, 9.5 years) had
      symptoms of recurrent abdominal pain (RAP syndrome) with or without vomiting, and
      the remaining 238 (age range, 3 to 18 years; mean age, 9.8 years) had no RAP (non
      RAP syndrome). We performed upper gastrointestinal endoscopy on 111 consecutive
      children of the 218 with RAP syndrome and obtained mucosal biopsies for culture,
      histologic analysis, CLO test (Delta West, Perth, Australia), and H pylori
      detection by polymerase chain reaction. RESULTS: Thirty-eight (17.4%) of 218
      children in the RAP group and 25 (10.5%) of 238 children in the non-RAP group
      were seropositive for H pylori. Of the 111 children endoscoped, 95 were found to
      be negative, and 12 were positive by all five assays. Specimens from 2 children
      were negative by culture and the CLO test but positive by the other three assays.
      Specimens from 1 child were negative by histologic analysis but positive by all
      other tests. The remaining child was positive for anti-H pylori IgG but negative
      by all of the other four assays. Upper gastrointestinal endoscopy detected 14
      children with peptic ulcer disease (9 duodenal ulcer and 5 gastric ulcer) and 12
      with antral nodular gastritis. Only 4 of the 14 diagnosed with peptic ulcer were
      H pylori positive by all five assays, whereas all 12 children with antral nodular
      gastritis were H pylori positive. Nine of the 12 H pylori-positive children were
      treated with a combination of bismuth subsalicylate, amoxicillin, and
      metronidazole for 2 weeks. Sera obtained at 2, 4, and 6 months after treatment
      from all 9 children showed a decrease in anti-H pylori IgG titer. Three H pylori
      infected children who did not receive any treatment served as control children,
      and their IgG levels remained elevated or increased over time. CONCLUSION: The
      results from our study indicate that screening for the serum IgG antibody to H
      pylori is a practical method for diagnosing H pylori infection in children, and
      that serial measurements of the H pylori IgG antibody are useful for monitoring
      treatment of H pylori because of its high sensitivity and ease of performance.
      Only 4 of the 14 children diagnosed with peptic ulcer disease were confirmed to
      be infected with H pylori, whereas all 12 children with antral nodular gastritis
      were found to be infected by H pylori. These observations suggest that H pylori
      infection is more frequently associated with gastritis than with peptic ulcer
      disease in children, and that H pylori gastritis is a cause of RAP syndrome in
      children.

PMID- 7630674
TI  - Independent parental administration of prednisone in acute asthma: a double
      blind, placebo-controlled, crossover study.
AB  - OBJECTIVE: To determine the effectiveness of a single dose of prednisone
      administered by a parent to a child early in an asthma attack. DESIGN: A
      randomized, double-blind, placebo-controlled, crossover study with children
      enrolled for 12 months (6 months prednisone, 6 months placebo). SETTING: A
      primary-care clinic and emergency department of an inner-city teaching hospital
      from March 1992 through May 1993. CHILDREN: Children 2 to 14 years of age
      enrolled in this clinic who had made two or more outpatient (emergency department
      or primary-care clinic) visits for acute asthma in the preceding year. SELECTION:
      There were 204 eligible children, of whom 86 were contacted and enrolled; of
      these, 78 (91%) completed the study. INTERVENTION: Capsules containing prednisone
      (2 mg/kg up to 60 mg) or placebo. Parents were instructed to give their child one
      capsule for an asthma attack that had not improved after a dose of the child's
      regular acute asthma medicine. MEASUREMENTS: Parents were interviewed every 3
      months. Computerized patient records and chart reviews were used to verify parent
      reports. Outcome measures were the numbers of outpatient visits and
      hospitalizations for treatment of acute asthma. RESULTS: Neither the total number
      of attacks nor the number for which medicine was used differed significantly by
      arm of study. There was a larger number of attacks resulting in outpatient visits
      when children were in the group that received prednisone (1.1 +/- 0.59 versus
      0.59 +/- 0.86). This trend was less pronounced but persisted when limited to
      attacks for which the medicine was given (0.58 +/- 0.99 versus 0.35 +/- 0.55).
      Neither the number of attacks resulting in admission nor the number of hospital
      days differed significantly by arm of study. CONCLUSIONS: A single dose of
      prednisone available for use at home early in an asthma attack was associated
      with an increase in outpatient visits made for acute asthma. When prednisone was
      given for an attack, there was no reduction in outpatient visits. This
      intervention can not be recommended for children with asthma. These results
      should be confirmed in other pediatric populations.

PMID- 7630675
TI  - The cost of implementation of the Clinical Laboratory Improvement Amendments of
      1988--the example of pediatric office-based cholesterol screening.
AB  - OBJECTIVE: To measure the additional costs of office-based laboratory testing due
      to the implementation of the Clinical Laboratory Improvement Amendments of 1988
      (CLIA '88), using cholesterol screening for children as an example. METHODS: Four
      to ten-year-old children who received their well child care at one of seven
      participating pediatric practices were screened for hypercholesterolemia. The
      average number of analyses per day and days per month were derived from the
      volume of testing completed by the practices. Nurses and technicians time in the
      screening process were measured and personnel costs were calculated based on
      salary and fringe benefit rates. Costs of supplies, analyzing control samples,
      instrument calibration, and instrument depreciation were included. Costs
      estimates of screening were then completed. CLIA '88 implementation costs were
      derived from appropriate proficiency testing and laboratory inspection programs.
      RESULTS: In six practices completing a low volume of testing, 2807 children (5 to
      6 children per week) were screened during the observation period, while 414
      (about 25 children per week) were screened in one high-volume practice
      implementing universal screening over a 4-month period. For the six low-volume
      practices, the cost of screening was $10.60 per child. This decreased to $5.47
      for the high-volume practice. Estimated costs of CLIA '88 implementation,
      including additional proficiency testing and laboratory inspection, added $3.20
      per test for the low-volume practices, and $0.71 per test for the high-volume
      testing. CONCLUSIONS: Implementation of CLIA adds significantly to the cost of
      office-based chemistry laboratory screening. Despite these additional expenses,
      the cost of testing is still within a reasonable charge for laboratory testing,
      and is highly sensitive to the volume of tests completed.

PMID- 7630676
TI  - A comparison of cathartics in pediatric ingestions.
AB  - OBJECTIVE: To compare the mean time to first stool, number of stools, and side
      effects of three commonly used cathartics in pediatric ingestions. DESIGN: This
      prospective clinical trial was a randomized, double-blinded comparison of
      sorbitol, magnesium citrate, magnesium sulfate, and water, administered with
      activated charcoal in the treatment of pediatric patients 1 to 5 years of age
      with acute ingestions. Outcome parameters were mean time to first stool, mean
      number of stools during 24 hours, and side effects. RESULTS: One hundred sixteen
      patients completed the study. Significant differences in mean time to the first
      stool were detected among cathartic agents (F = 9.29), with sorbitol-treated
      patients having a shortest mean time to the first stool (mean, 8.48 hours).
      Sorbitol produced a significantly higher number of stools (mean, 2.79) in the 24
      hour follow-up period than other cathartics (F = 3.49). The most common side
      effect of cathartic administration was emesis, which occurred more commonly in
      sorbitol-treated patients. CONCLUSION: Sorbitol, when administered with activated
      charcoal in the treatment of children with acute ingestions, produced a shorter
      time to first stool and more stools than magnesium citrate, magnesium sulfate, or
      water.

PMID- 7630677
TI  - Familial hypercholesterolemia: molecular, biochemical, and clinical
      characterization of a French-Canadian pediatric population.
AB  - BACKGROUND: Familial hypercholesterolemia (FH) is a dominantly-inherited disorder
      attributable to a defect in the low-density lipoprotein (LDL) receptor gene. Five
      mutations at this locus have been identified in French-Canadians. In children, it
      may be difficult to clinically distinguish FH from other forms of polygenic or
      monogenic hyperlipidemia. Therefore, our objectives were to define the molecular
      basis of our subjects' hypercholesterolemia, to characterize their biochemical
      phenotype in relation to the underlying molecular defect, and to assess their
      response to chronic dietary therapy. METHODS: We studied 88 unrelated French
      Canadian children with a persistent increase in LDL cholesterol and a parental
      history of hyperlipidemia. Baseline and end-of-diet lipid and apolipoprotein
      levels were measured. Mutational analysis at the LDL receptor gene locus was
      performed. RESULTS: Heterozygosity for the common French-Canadian LDL receptor
      gene > 10-kb deletion was found in 57% of subjects (group 1), 14% carried one of
      the other four previously characterized LDL receptor gene mutations (group 2),
      and none of the five molecular defects tested was detected in 29% (group 3).
      Total cholesterol, LDL cholesterol, and apolipoprotein B baseline levels were
      similar among these three groups but significantly higher than in control
      subjects. However, there was wide interindividual variability even among those
      carrying the same mutation. Significantly lower baseline levels of high-density
      lipoprotein cholesterol and apolipoprotein A1 were found in group 1 compared with
      group 3 and the controls. The response to diet was similar among the three groups
      with an average reduction in the mean level of total cholesterol of 4.4%.
      CONCLUSIONS: The frequency of proven FH heterozygotes (71%) was remarkable in the
      pediatric population studied. Our data suggest that, in children, a persistent
      primary increase in LDL cholesterol associated with a parental history of
      hyperlipidemia is a good predictor of an underlying monogenic disorder as opposed
      to a polygenic disorder, at least in French-Canadians. Only molecular analysis
      allowed us to unequivocally define the cause of our patients'
      hypercholesterolemia. Most children with familial hyperlipidemia did not reach
      desirable plasma lipid levels solely under diet therapy.

PMID- 7630678
TI  - A phase I/II evaluation of stavudine (d4T) in children with human
      immunodeficiency virus infection.
AB  - OBJECTIVES: To determine the pharmacokinetic properties, tolerance, safety, and
      preliminary activity of stavudine in human immunodeficiency virus (HIV)-infected
      children. DESIGN: Phase I/II, open and dose-ranging (0.125 to 4 mg/kg/day in two
      divided doses). PATIENTS: Thirty-seven HIV-infected children (median age, 5.5
      years; range, 7 months to 15 years) with a median CD4+ lymphocyte count at
      baseline of 242 cells/microL (range 2 to 2290 cells/microL). Thirty children had
      symptomatic HIV disease at entry; seven had HIV-related immunosuppression alone.
      Twenty-nine subjects had a history of prior zidovudine (ZDV) therapy. RESULTS: As
      compared with adults receiving the same weight-adjusted doses, the children we
      studied had lower maximum observed stavudine plasma concentrations (CMAX) and
      area under the plasma concentration versus time curves (AUC), and more rapid
      stavudine elimination. The absolute oral bioavailability of the drug ranged from
      61% to 78%. There was no plasma accumulation of the drug between day 1 and week
      12. Week 12 cerebrospinal fluid stavudine concentrations in seven subjects,
      obtained approximately 2 to 3 hours after oral doses, ranged from 16% to 97% of
      concomitant plasma concentrations. Stavudine was well-tolerated and there were no
      dose-related clinical or laboratory adverse events. One subject with baseline
      neurologic abnormalities experienced a transient episode of apparent pain or
      discomfort in her fingers, possibly related to stavudine. All other adverse
      events were attributed to underlying disease. Stavudine activity, measured
      indirectly by CD4+ lymphocyte count and serum p24 antigen concentration changes,
      was observed in some subjects. Progression of HIV disease and survival correlated
      with prior ZDV therapy, HIV disease classification, baseline CD4+ lymphocyte
      count, and weight growth velocity. CONCLUSIONS: Stavudine appears to hold promise
      for the treatment of HIV infection in children. Its pharmacokinetic properties
      are consistent and predictable, and it appears to be remarkably well-tolerated
      and safe. Although our study was not designed to assess the drug's efficacy,
      preliminary clinical and laboratory evidence of activity was observed.

PMID- 7630679
TI  - One-year changes in weight and fatness in girls during late adolescence.
AB  - OBJECTIVE: To document postmenarcheal growth and changes in weight and fatness in
      girls. DESIGN: Mixed longitudinal study to determine yearly growth increments.
      PARTICIPANTS: Six hundred sixty-eight postmenarcheal girls, initially ages 13 to
      17 years, from two Philadelphia high schools. Overall, 61.4% of the girls were
      white, 15.7% black, 16.8% Puerto Rican Hispanic, and 6.1% of other ethnicities
      (non-Puerto Rican Hispanic or Asian). OUTCOME MEASURES: Height (in centimeters),
      weight (in kilograms), and triceps and subscapular skinfold thicknesses (in
      millimeters) were measured initially and after 1 year. The anthropometric
      measures were analyzed both cross-sectionally by age cohort and longitudinally.
      RESULTS: Viewed cross-sectionally by chronologic age groups and adjusted for
      ethnicity, gynecologic age, cigarette smoking, and late maturation (menarche > or
      = 14 years), there were no statistically significant trends with age in height,
      weight, body mass index (kilograms per m2), triceps, or subscapular skinfold
      thicknesses. Nevertheless, there were significant trends in velocity with
      increasing chronologic age. On the average, postmenarcheal girls gained about 6.5
      kg (14.3 lb) during late adolescence from about 1.5 years after menarche to age
      18 years. Height and triceps skinfolds showed significantly decreasing
      velocities, whereas there was a significant monotonic increase in velocity with
      age for skinfolds at the subscapular site. CONCLUSIONS: Even with normal weight
      gain during late adolescence in girls, there seems to be greater potential for
      fat deposition centrally. Thus, excessive weight gain during late adolescence may
      exacerbate the normal processes of fat deposition, leading to large gains in
      central fat, and thereby increasing the long-term risk for metabolic and
      cardiovascular diseases later in life.

PMID- 7630680
TI  - Neurologic manifestations of in utero cocaine exposure in near-term and term
      infants.
AB  - OBJECTIVE: To determine whether the incidence of neurosonographic and neurologic
      abnormalities is higher in cocaine-exposed infants at birth. METHODS: In utero
      exposure to cocaine was investigated in 39 term and near-term infants with
      positive urine screens for cocaine only and 39 matched control infants without
      drug exposure admitted to the regular term newborn nursery. Serial evaluations
      were performed on each infant on postnatal days 1 and 2 and included a cranial
      sonogram, a neurologic and behavioral assessment for drug withdrawal, and Doppler
      interrogation of the anterior and middle cerebral arteries. RESULTS: There were
      no differences between groups in neurosonographic abnormalities. Grade I or II
      intraventricular hemorrhage occurred in 11% of cocaine-exposed and 11% of control
      infants. There were no cases of grade III intraventricular hemorrhage, cystic
      periventricular leukomalacia, or neonatal stroke. Head size was smaller in
      cocaine-exposed infants, ie, 32.7 +/- 0.1 cm versus 33.8 +/- 0.1 cm. The
      neurologic examination was similar between groups with regard to tone, reflexes,
      and cranial nerves. Behavioral scores were higher on both days, in cocaine
      exposed versus control infants, ie, 4.4 +/- 0.5 versus 2.7 +/- 0.03 on day 1 and
      5.0 +/- 0.5 versus 1.71 +/- 0.31 on day 2. Cerebral blood flow velocity
      measurements in the anterior cerebral artery were similar between groups on both
      days of examination. However, cocaine-exposed infants demonstrated a significant
      increase in flow velocity from day 1 to day 2, ie, 0.48 +/- 0.03 to 0.57 +/-
      0.04. There was a concomitant decrease in the pulsatility index from day 1 to day
      2 in the cocaine-exposed, ie, 0.74 +/- 0.02 to 0.69 +/- 0.02, but not in the
      control infants. No differences were noted in the flow velocities in the middle
      cerebral arteries between groups. CONCLUSIONS: Term and near-term infants
      admitted to a regular nursery who are exposed to cocaine in utero: (1) do not
      exhibit an increased incidence of neurosonographic abnormalities; (2) do exhibit
      altered behavior consistent with drug withdrawal; and (3) do demonstrate changes
      in flow velocity in the anterior cerebral artery consistent with the
      vasoconstrictive effects of the drug. However, these changes were not accompanied
      by changes in the neurologic examination or altered care. The long-term
      neurodevelopmental implications of these subtle abnormalities in the neonatal
      period remain to be determined.

PMID- 7630681
TI  - Semiquantitative study of tinea capitis and the asymptomatic carrier state in
      inner-city school children.
AB  - OBJECTIVE: To quantify and characterize the asymptomatic carrier state of tinea
      capitis in school children from the inner city. METHODS: All students attending a
      parochial school (kindergarten through seventh grade) in the city of Philadelphia
      were cultured for tinea capitis periodically over 16 months (1404 hemi-scalp
      cultures from 224 children). RESULTS: Our initial prevalence study of this all
      black population (ages 5 to 13 years) found a 3% rate of index cases
      (symptomatic) and a 14% rate of asymptomatic carriers (without black-dot lesions,
      obvious hair loss, scaling, crusts, pustules, or erythema). Trichophyton
      tonsurans was the predominant dermatophyte (96% of 125 positive cultures;
      Microsporum canis was the only other isolate). Fifty percent of all positive
      cultures came from children in kindergarten and first grade; first grade had the
      highest rate of index cases. The overall prevalence of asymptomatic carriers was
      not higher in the classes containing index cases. Fifty-nine percent of
      asymptomatic carriers had a 1+ spore load (1 to 10 colonies isolated per scalp),
      while 74% of index cases had a 4+ spore load (> 150 total colonies). Forty-five
      untreated asymptomatic carriers were followed for 2 to 5 months: 19 (42%) became
      culture-negative; of these, 17 (90%) had a 1+ spore load. CONCLUSIONS: We found
      that inner-city black school children who are asymptomatic carriers of T
      tonsurans had lower spore loads than index cases. Index cases did not appear to
      be the primary mode of transmission within a classroom. More than half of
      untreated asymptomatic carriers remained culture-positive after 2 months and
      probably play a role in the transmission of tinea capitis within this population.

PMID- 7630683
TI  - Adolescent development and transitions to motherhood.
AB  - OBJECTIVE: To use both qualitative and quantitative methods to examine the
      experience of motherhood during adolescence and to evaluate developmental
      influences on the concept of maternal role. DESIGN: (1) A grounded theory
      approach was initially used to generate a hypothesis. Focus groups and individual
      interviews were analyzed for concept and theme. (2) A quantitative method using
      correlational analysis was used to test the hypothesis generated by qualitative
      study. A structured interview using five specific, scored questions about self
      and about motherhood was used to examine the relationship between developmental
      complexity of responses to questions about self and questions about motherhood.
      SETTING AND PARTICIPANTS: The qualitative study involved group and individual
      interviews with 42 teenage mothers. The quantitative study involved individual
      interviews with 25 mothers, ages 14 to 18 years, at an innercity clinic for young
      parents and their infants. Race and ethnicity were heterogeneous, and 100%
      received Aid to Families With Dependent Children. RESULTS: The major hypothesis
      generated from the qualitative analysis was that an adolescent mother's
      conceptualization of her maternal role is related to her own psychosocial and
      cognitive development. The quantitative study revealed a strong correlation
      between the developmental complexity of responses to questions about self and the
      complexity of responses to questions about motherhood (r2 = .81). CONCLUSION: The
      experience of motherhood and the conceptualization of the maternal role in
      adolescence is related to young mothers' psychosocial cognitive development.

PMID- 7630682
TI  - High-risk behaviors among high school students in Massachusetts who use anabolic
      steroids.
AB  - OBJECTIVE: To assess the association between the frequency of anabolic steroid
      use and the frequency of other health risk and problem behaviors among high
      school students in Massachusetts. METHODS: The 1993 Massachusetts Youth Risk
      Behavior Survey was conducted on a random sample of 3054 high school students
      (49% male; mean age, 16 +/- 1.2 years). The frequency of lifetime anabolic
      steroid use was measured on an ordinal scale from 1 to 6, representing "0" to "40
      or more times." Other health risk and problem behaviors measured were sexual
      behaviors, suicidal behaviors, frequency of not wearing a passenger seat belt,
      riding a motorcycle, not wearing a helmet while riding a motorcycle, driving
      after drinking alcohol, riding with a driver who had been drinking alcohol,
      fighting, and carrying a weapon. The associations between the frequency of
      anabolic steroid use and other high-risk behaviors were determined using the
      Spearman correlation coefficient for ordinal data and the Kruskall-Wallis
      analysis of variance for categorical data. Representative indicators of each risk
      behavior significantly associated with anabolic steroid use were then analyzed
      using a stepwise multiple-regression analysis. RESULTS: The frequency of anabolic
      steroid use was associated with all of the other high-risk behaviors analyzed.
      Using multiple-regression analysis, driving after drinking alcohol accounted for
      12.5% of the variance of the model. Carrying a gun, the number of sexual partners
      within the past 3 months, not using a condom during last intercourse, injury in a
      physical fight requiring medical attention, history of a sexually transmitted
      disease, not wearing a helmet on a motorcycle, not wearing a passenger seatbelt,
      and a suicide attempt requiring medical attention accounted for an additional
      9.0% of the variance. The full model accounted for greater than 21% of the
      variation. CONCLUSIONS: The frequency of anabolic steroid use among adolescents
      is associated with other high-risk behaviors, thus supporting the hypothesis that
      anabolic steroid use is part of a "risk behavior syndrome" rather than an
      isolated behavior. This finding emphasizes the need for comprehensive high-risk
      behavior screening and counseling among teens who use anabolic steroids.

PMID- 7630684
TI  - A population-based study of severe firearm injury among children and youth.
AB  - BACKGROUND: Firearm injuries are a major cause of pediatric mortality and
      morbidity in the United States. To date, population-based studies describe the
      epidemiology of firearm-related deaths; however, the patterns of severe, nonfatal
      pediatric firearm-related injuries are not as well defined. OBJECTIVES: To
      determine the epidemiology of severe firearm-related deaths and injuries among a
      statewide population of children and youth ages birth to 19 years. METHODS:
      Demographic, geographic, and cost data were analyzed from Connecticut death
      certificates for 1988 through 1992 and hospital discharge data for 1986 through
      1990 for firearm-related unintentional, self-inflicted, and assaultive injury
      among children and youth ages birth to 19 years. RESULTS: There were 219 firearm
      deaths: 68% homicides, 25% suicides, 6% unintentional, and 1% of undetermined
      intent, resulting in an annual age-specific death rate of 6.6 per 100,000
      persons. There were 533 hospitalizations for gunshot wounds (16 per 100,000); 41%
      were assaults, 1% suicide attempts, 39% unintentional gunshot wounds, 1% legal
      interventions, and 18% of undetermined intent. More than 80% of deaths from
      gunshot wounds and hospitalizations occurred among 15- to 19-year-old males, most
      occurring in Connecticut's five largest cities. Most firearm homicides occurred
      among urban residents; most firearm suicides occurred among nonurban residents;
      and unintentional shootings were evenly distributed between urban and nonurban
      residents. The total cost of firearm-related hospitalizations averaged $864,000
      per year. CONCLUSIONS: Firearms are a major cause of mortality and morbidity of
      Connecticut children and youth, exceeded only by motor vehicles as a cause of
      death among those 1 to 19 years of age. Handguns were responsible for a
      disproportionate amount of trauma compared with other firearm types. The
      epidemiology of pediatric gunshot injuries requires a range of strategies for
      prevention. Physicians caring for families with children must include firearm
      injury prevention counseling as a routine part of anticipatory guidance.

PMID- 7630685
TI  - Evaluation of a subsidy program to increase bicycle helmet use by children of low
      income families.
AB  - OBJECTIVE: We have previously shown that an educational program was not effective
      in increasing bicycle helmet use in children of low-income families. The
      objective of this study was to evaluate a combined educational and helmet subsidy
      program in the same population, while controlling for secular trends. The
      secondary objective was to complete a third year of surveying children's bicycle
      helmet use throughout the study community. DESIGN: A prospective, controlled,
      before-and-after study. SUBJECTS: Bicycling children 5 to 14 years of age from
      areas of low average family income. SETTING: A defined geographic community
      within a large urban Canadian city. INTERVENTION: In April 1992, students in
      three schools located in the area of lowest average family income were offered
      $10 helmets and an educational program; three other low-income areas served as
      control areas. MAIN OUTCOME MEASURE: Helmet use was determined by direct
      observation of more than 1800 bicycling children. RESULTS: Nine hundred ten
      helmets were sold to a school population of 1415 (64%). Reported helmet ownership
      increased from 10% to 47%. However, observed helmet use in the low-income
      intervention area was no different from the rate in the three low-income control
      areas (18% versus 19%). There was no difference in the trend in helmet use during
      the period of 1990 through 1992 in the intervention area (4% to 18%) compared
      with the control areas (3% to 19%). Helmet use rates from all income areas have
      increased from 3.4% in 1990, to 16% in 1991, to 28% in 1992. In 1992, helmet use
      in the high-income areas was 48% and in the low-income areas was 20%.
      CONCLUSIONS: There has been a trend toward increasing helmet use in all income
      areas during the 3-year period. Despite encouraging helmet sales and increases in
      reported helmet ownership, the results of the observational study do not support
      the efficacy of a helmet subsidy program in increasing helmet use in children
      residing in areas of low average family income. Strategies to increase helmet use
      in children of low average family income remain a priority.

PMID- 7630686
TI  - Oxygen desaturation of selected term infants in car seats.
AB  - OBJECTIVES: Premature infants are known to be at risk for oxygen (O2)
      desaturation and/or apnea in car seats. Since 1990, the American Academy of
      Pediatrics has recommended a period of monitoring in car seats before hospital
      discharge for infants born at < 37 weeks gestation. The objective of this report
      is to determine if selected term infants are also at risk for O2 desaturation,
      apnea, or bradycardia while in an infant car seat. METHODS: MetroWest Medical
      Center is a community hospital with a level II neonatal unit. Term infants who in
      the judgment of their pediatrician were felt to be at risk for O2 desaturation or
      apnea were monitored for a 90-minute period in a car seat and observed for
      transcutaneous O2 desaturation, apnea, or bradycardia. In addition, several
      infants who were admitted to the pediatric inpatient unit after discharge from
      the nursery were monitored in a similar fashion. RESULTS: Eight of 28 monitored
      infants (28.6%) had a period of O2 desaturation < 90%. In addition, five of 28
      monitored infants (17.8%) had borderline results (O2 saturation, 90 to 93%). All
      four infants monitored because of genetic syndromes had abnormal results. O2
      desaturation was also observed in two term infants who had been observed to be
      apneic by a parent after discharge from the nursery. CONCLUSIONS: In selected
      circumstances (eg, genetic disorders or observed apnea) term infants may be at
      risk for O2 desaturation in an upright car seat and monitoring these infants in
      car seats before nursery discharge should be considered. Because not all infants
      at risk for O2 desaturation can be identified at birth, an alternative approach
      would be to recommend, unless medically contraindicated (eg, gastroesphogeal
      reflux when supine), that infants should routinely be transported in a supine
      position car seat in the early months of life.

PMID- 7630687
TI  - Childhood thrombosis.
AB  - OBJECTIVE: The objective of our study was to evaluate the age, sex, clinical
      conditions, family history, site, catheter association, means of radiologic
      evaluation, development of pulmonary involvement, prevalence of antithrombin III,
      protein C and protein S deficiencies, and lupus anticoagulants in children who
      suffered a thrombotic event. METHODS: Data were collected on children over 1
      month of age who had or developed a thrombotic event from 1987 through 1993 at
      two pediatric centers. RESULTS: Sixty-one children (mean age, 10 years) suffered
      a thrombotic event. Males and females were equally affected. A variety of
      clinical prothrombotic conditions similar to those described in adults could be
      identified for two thirds of the children. Family history was positive in seven
      children. The primary thrombotic site for two thirds of the children was the
      central nervous system and other centrally located blood vessels. Diagnosis of
      the primary thrombotic site was primarily by ultrasound. A central vascular
      access device was associated with 25% of thromboses. Lung involvement occurred in
      20%. Two thirds of the children were evaluated for a lupus anticoagulant and a
      deficiency of protein C and protein S; two thirds had one of these diagnosed. For
      further analyses, children without an underlying prothrombotic systemic illness
      or precipitant at the time of thrombosis (n = 20) were compared to those with
      these conditions (n = 41). Central nervous system thromboses were significantly
      increased in the children without prothrombotic conditions. The prevalence of a
      deficiency of protein C or protein S or the presence of a lupus anticoagulant
      approached 90% in the group without prothrombotic conditions as compared with 50%
      in the other group. CONCLUSION: We conclude that prospective multicenter
      pediatric thrombosis studies are warranted to confirm our preliminary findings of
      a high incidence of lupus anticoagulants and protein C and protein S deficiency
      in children with thromboses.

PMID- 7630688
TI  - Factors related to immunization status among inner-city Latino and African
      American preschoolers.
AB  - OBJECTIVE: To identify factors associated with undervaccination at 3 months and
      24 months among low-income, inner-city Latino and African-American preschool
      children. DESIGN: Interviews with a representative sample of inner-city families
      using a cross-sectional, multi-stage, cluster-sample design combined with a
      replicated quota sampling approach. SETTING: South Central and East Los Angeles
      areas in inner-city Los Angeles. POPULATION: Eight hundred seventeen Latino and
      387 African-American families with children between 12 and 36 months of age. MAIN
      OUTCOME VARIABLES: Being fully immunized or up-to-date (UTD) at 3 months (1
      diphtheria-tetanus-pertussis vaccine and 1 oral polio vaccine) and 24 months of
      age (4 diphtheria-tetanus-pertussis vaccines, 3 oral polio vaccines, and 1
      measles-mumps-rubella vaccine). METHODS: Logistic regressions of UTD immunization
      status at 3 and 24 months by population and health care system factors. RESULTS:
      Seventy percent of Latino children and 53% of African-American children were UTD
      at 3 months of age. At 24 months of age, 42% of Latino children and 26% of
      African-American children were UTD on their immunizations. Receipt of the first
      immunizations by 3 months was associated with smaller family size, and evidence
      of connection to prenatal care. Latino children were less likely to be UTD at 24
      months if they obtained well child care from private providers versus public
      clinics (odds ratio [OR] = 0.45, 95% confidence interval [CI] = 0.26, 0.79).
      There was also a trend for Latino children to be less well immunized if they were
      in health maintenance organizations versus public clinics (0.31, 0.05 < P < .1).
      African-American children were more likely to be UTD at 24 months if they were
      UTD at 3 months (OR = 5.56, 95% CI = 1.43, 21.6), had more health visits (OR =
      1.13, 95% CI = 1.01, 1.27), and were less likely to be UTD at 24 months if they
      were on Medicaid versus private insurance (OR = 0.26, 95% CI = 0.08, 0.90).
      IMPLICATIONS: Both African-American and Latino children in inner-city Los Angeles
      have low immunization rates at 3 and 24 months. Prenatal care and family size are
      strongly associated with being UTD by 3 months; however, family and child
      characteristics are relatively unimportant predictors of being UTD at 24 months
      of age. Important risk factors for underimmunization at 2 years of age in the
      inner-city, low-income communities studied include type of health insurance and
      source of well child care, with the public sector having higher rates than
      private doctors' offices or health maintenance organization/managed care plans.

PMID- 7630689
TI  - Psychosocial adaptation of 39 adolescents with sex chromosome abnormalities.
AB  - OBJECTIVES: Children with sex chromosome abnormalities (SCA) are known to be at
      increased risk for neuromotor, language, learning, and behavioral problems, but
      little is known of psychosocial adaptation of SCA adolescents. This study was
      conducted to evaluate psychologic characteristics of unselected SCA adolescents,
      including socialization, educational progress, separation from family, and
      incidence and severity of psychiatric disturbance. METHODS: Thirty-nine propositi
      identified through the screening of 40,000 consecutive Denver newborns, including
      boys with 47,XXY karyotypes and girls with 47,XXX, 45,X, and partial X monosomy,
      or SCA mosaic karyotypes, have been followed longitudinally into adolescence.
      Twenty-seven siblings served as controls. Between 12 and 19 years of age, all
      participated in blind psychiatric interviews and were administered standardized
      intelligence and achievement tests. RESULTS: SCA propositi demonstrated a mean IQ
      score 21 points lower than that of control subjects. In addition, lower mean
      scores were seen on achievement test results as well as lower overall
      psychosocial adaptation scores and increased incidence of psychiatric
      disturbance. Depression was the most frequent psychiatric diagnosis. Propositi
      were more likely to receive special education assistance in high school and were
      less likely to graduate from high school than were controls. Of the three
      nonmosaic propositi groups, the 47,XXX girls demonstrated the poorest overall
      psychosocial adaptation and highest degree of psychiatric disturbance. Mosaic
      girls were indistinguishable from control subjects. Marked variability was found
      among all three nonmosaic groups, with some individuals in each group
      demonstrating relatively strong psychosocial adaptation. CONCLUSIONS: The
      presence of nonmosaic sex chromosome abnormality increases the risk for impeded
      cognitive skills, learning abilities, and psychosocial adaptation in adolescence.
      The factors that allow for stronger adaptation in some of these adolescents
      include the presence of a stable and supportive family environment. The outlook
      for adaptation in unselected SCA adults remains uncertain.

PMID- 7630690
TI  - The hair collar sign: marker for cranial dysraphism.
AB  - OBJECTIVE: To call attention to a cutaneous marker for neural tube closure
      defects of the scalp, the "hair collar" sign. This finding consists of a ring of
      long, dark, coarse hair surrounding a midline scalp nodule. METHODS AND RESULTS:
      Four children with small congenital scalp nodules and the hair collar sign were
      studied from the standpoint of clinical findings, radiologic scans, and histology
      of the excised nodules. All four had an overlying vascular stain in addition to
      the hair collar. Patients 1 and 2 were found to have encephaloceles, and one had
      heterotopic brain tissue. The fourth family refused surgery, but the clinical and
      radiologic findings were consistent with a diagnosis of atretic encephaloceles.
      One infant had agenesis of the corpus callosum and a Dandy-Walker malformation as
      associated findings. CONCLUSIONS: The "hair collar" sign should alert the
      pediatrician to the possibility of ectopic neural tissue in the scalp and/or
      underlying central nervous system malformations.

PMID- 7630691
TI  - The relationship of selenium status to respiratory outcome in the very low birth
      weight infant.
AB  - OBJECTIVE: To examine the relationship between plasma and erythrocyte selenium
      and glutathione peroxidase (GPx) levels in premature infants and outcome
      measures. DESIGN: Prospective observational longitudinal study. SETTING: Two
      regional neonatal intensive care units in the South Island of New Zealand, an
      area with low soil selenium. PATIENTS: Seventy-nine infants with birth weights
      less than 1500 g or gestation less than 32 weeks admitted within 48 hours of
      birth from November 1992 through November 1993. MAIN OUTCOME MEASURES: Oxygen
      requirement at 28 days (chronic lung disease), or 36 weeks postmenstrual age and
      for all or most of the time from birth (bronchopulmonary dysplasia), total days
      in oxygen, retinopathy of prematurity, periventricular hemorrhage, or ventricular
      dilatation. RESULTS: Initial infant plasma selenium and GPx levels were about two
      thirds of maternal levels and fell a further 30% in 28 days. In contrast to
      adults, there was a poor correlation in infant plasma between selenium and GPx at
      birth and 28 days. Plasma selenium at 28 days was significantly lower in infants
      with chronic lung disease and bronchopulmonary dysplasia. After controlling for
      gestational age and age when fully fed orally, 28-day plasma selenium was
      significantly associated with the log of total days of oxygen requirement, each
      drop of 0.1 mumol/L in 28-day selenium being associated with a 58% increase in
      days of oxygen dependency. No significant associations of other parameters of
      selenium status and respiratory outcome were found, and there were no significant
      associations of any parameters of selenium status with other outcome measures.
      CONCLUSIONS: This study demonstrates for the first time in human infants that low
      plasma selenium levels are significantly associated with an increased respiratory
      morbidity. Whether selenium deficiency is etiologically important in determining
      the respiratory outcome or the result of sickness in the infant should be
      investigated in a randomized, controlled trial.

PMID- 7630692
TI  - Effects of late-afternoon methylphenidate administration on behavior and sleep in
      attention-deficit hyperactivity disorder.
AB  - OBJECTIVE: This study evaluated the effects on behavior and sleep of
      methylphenidate (MPH) administered at 4 PM to children with attention-deficit
      hyperactivity disorder (ADHD). METHODOLOGY: Twelve children admitted to a child
      psychiatric inpatient service with ADHD participated in a double-blind, crossover
      study in which they received a 4 PM dose of either 15 mg of MPH, 10 mg of MPH, or
      a placebo in random order for 12 consecutive days. Ratings of behavior, including
      ADHD symptoms, pertaining to the period from dose administration until sleep
      onset, were supplied nightly by hospital staff. Sleep latency and sleep adequacy
      were also assessed for each night. RESULTS: MPH resulted in markedly improved
      behavioral control compared with placebo; there was no difference between 15-mg
      and 10-mg MPH doses. MPH did not alter sleep latencies observed with the placebo.
      Children were more often rated as less tired on awakening after nights that they
      received 10 mg of MPH compared with 15 mg of MPH and the placebo. Weight loss was
      apparent among 83% of the patients, but dinner intake did not vary with third
      dose condition. CONCLUSIONS: Morning and noon administration of stimulants to
      children with ADHD is a near-universal practice, but many clinicians avoid a
      third, late-afternoon administration for fear of inducing insomnia. This study's
      findings show that children with ADHD derive substantial symptom reduction from
      MPH administered in late afternoon, with no untoward effects on sleep. Therefore,
      three-times-a-day dosing should be considered for those children exhibiting ADHD
      symptoms in the evening. Adverse effects on sleep latency were not apparent in
      the sample overall. Nonetheless, monitoring for possible aggravation of sleep
      problems and weight loss remains sound treatment practice.

PMID- 7630693
TI  - Training pediatric residents to prevent tobacco use.
AB  - OBJECTIVE: To assess the effectiveness and acceptability of incorporating the
      National Cancer Institute (NCI) Guide to Preventing Tobacco Use During Childhood
      and Adolescence into pediatric training. DESIGN: Preintervention and
      postintervention self-reported surveys for residents receiving training and
      postintervention baseline surveys for those residents not receiving training.
      Measures include: (1) a self-reported knowledge, attitude, and behavior survey of
      residents; and (2) physician behavior reports from parent exit interviews.
      SETTING: A hospital-based pediatric residency program and continuity clinic.
      SUBJECTS: Pediatric residents and parents of pediatric patients seen for well
      child examinations. INTERVENTIONS: Structured NCI smoking cessation curriculum
      modified for delivery during scheduled teaching activities. RESULTS: The NCI
      training was acceptable and perceived as important by residents. Many did not
      recall receiving the materials or training. Trained residents who remembered the
      intervention improved their smoking cessation counseling effectiveness. Most
      patients' parents think it appropriate for physicians to ask; however, most
      reported not having been asked about smoking or environmental smoke exposure.
      CONCLUSIONS: For residents to learn effective prevention counseling strategies,
      systematic, reinforced preventive educational curricula must become an
      institutionalized part of residency training.

PMID- 7630694
TI  - Acute and chronic intestinal motor activity responses to two infant formulas.
AB  - OBJECTIVE: Preterm formulas are nutritionally better for preterm infants;
      however, it has been observed that these formulas cause more feeding intolerance
      than do regular formulas. Because intestinal motor activity is responsible for
      the aboral movement of intraluminal nutrients, the purpose of this study was to
      evaluate intestinal motor activity responses to two infant formulas: 84 and 100.8
      J/oz. STUDY DESIGN AND RESULTS: Intestinal motor activity was recorded in 52
      preterm infants who had never been fed and who were randomly assigned to receive
      small enteral feedings (24 mL/kg per day) for 10 days with one of two commonly
      used infant formulas. In a subset of 26 of these infants, acute motor responses
      to both formulas were also evaluated. At the end of the study period, motor
      activity during fasting did not differ between the two groups of infants.
      However, motor responses during feeding to the two formulas differed
      significantly. When infants were fed for the first time, their motor activity
      increased compared with fasting when they were fed the 84-J/oz formula but
      decreased when they were fed the 100.8-J/oz formula. These differences in motor
      responses to the two formulas were not present 10 days later. These differences
      in motor responses to the 100.8- and 84-J/oz formulas were even more pronounced
      among the 7 infants who subsequently developed feeding intolerance to the 100.8
      J/oz formula during the 10-day study period. CONCLUSION: Inhibition of motor
      responses to calorically denser formulas during active feeding in a subset of
      preterm infants may underlie the feeding intolerance they experience when they
      are fed these formulas. However, this inhibitory response diminishes with age,
      suggesting that denser formulas can be reintroduced later in life to these
      infants.

PMID- 7630695
TI  - Disciplining young children: the role of verbal instructions and reasoning.
AB  - Pediatricians are often asked to advise parents who are having difficulty
      managing the oppositional behaviors of their toddlers and preschool-age children.
      A large number of articles provide advice to pediatricians and parents on
      effective disciplinary strategies. However, despite the fact that verbal
      explanations, reasoning, and instructions are commonly used by parents, few
      articles directly address the use of these strategies to affect children's
      behavior. In this paper, we review studies that explicitly investigate the
      ability of adults' verbal explanations or instructions to alter the behavior of
      young children. These studies suggest that under most circumstances, verbal
      explanations and instructions are not effective in changing young children's
      problem behaviors. We then discuss how theories in developmental and behavioral
      psychology help explain the limitations of using verbal reasoning and
      instructions to change young children's problem behaviors. Finally, we provide
      some recommendations for parents on the use of verbal explanations and
      instructions in disciplining young children.

PMID- 7630696
TI  - E.H. Christopherson Lecture: lessons for the United States From the Worldwide
      Child Survival Revolution.
AB  - It is time to apply in the United States' principles that are emerging from a
      series of World Summits and United Nations Conference on Children, Environment,
      Population, Women, and Social Development. After years of top-down programs
      supported by international agencies, which have made some significant
      contributions in promoting activities such as childhood immunization but are
      having problems of sustainability, we need to focus now on integrated human
      development. The past tendency in international assistance to concentrate on
      economic development has not helped the people in greatest need. There is growing
      realization that what improves the quality of life most is what people do for
      themselves. Sustainability requires social mobilization at the local level. There
      are thousands of integrated, social development projects around the world that
      demonstrate the power of community-based, participatory approaches and we know
      how such local programs can be made to work under any political or economic
      system. What we haven't learned is how to "go to scale" in extending such
      projects to cover larger populations. A promising approach seems to be using
      successful local projects upgraded into Centers for Action Learning to promote
      the adaptation of science-based innovations to everyday life in a whole region of
      a country.

PMID- 7630697
TI  - Steroids and asthma.

PMID- 7630698
TI  - A single shot at Salmonella typhi: a new typhoid vaccine with pediatric
      advantages.

PMID- 7630699
TI  - Extraordinarily high eosinophilia and elevated serum interleukin-5 level observed
      in a patient infected with Paragonimus westermani.
AB  - OBJECTIVE: Although eosinophilia is one of the typical clinical features of some
      helminth infections, the degree of eosinophilia in helminthiasis is usually 10%
      to 30% with a total white blood cell count of 10,000 to 20,000/mm3. Here we
      report a case of extraordinarily high eosinophilia (91%; absolute eosinophil
      count, 84,000/mm3) caused by Paragonimus westermani infection. To determine the
      mechanisms of eosinophilia, the levels of several eosinophilopoietic cytokines in
      the patient's sera were measured during the course of treatment. METHODS: Serum
      levels of three cytokines, granulocyte-macrophage colony-stimulating factor,
      interleukin-3 (IL-3), and IL-5 were measured by enzyme-linked immunosorbent assay
      using commercial kits or our own assay system for IL-5. RESULTS: Although the
      kinetic changes of IL-5 correlated well with eosinophilia, the serum IL-3 level
      remained below the detection level throughout the period examined. Although the
      granulocyte-macrophage colony-stimulating factor level was twofold to threefold
      higher than the normal level, its kinetics did not parallel the degree of
      eosinophilia. CONCLUSIONS: These results show that Paragonimus westermani
      infection can induce an extraordinarily high level of eosinophilia with an
      associated increase in IL-5 production. Immunoserologic diagnosis for parasitic
      diseases should be included in the differential diagnosis of eosinophilia.

PMID- 7630700
TI  - Lemierre's syndrome in adolescent children--anaerobic sepsis with internal
      jugular vein thrombophlebitis following pharyngitis.

PMID- 7630701
TI  - Implementation of the immunization policy (S94-26). American Academy of
      Pediatrics Committee on Practice and Ambulatory Medicine.

PMID- 7630702
TI  - The initiation or withdrawal of treatment for high-risk newborns. American
      Academy of Pediatrics Committee on Fetus and Newborn.

PMID- 7630703
TI  - Drug-exposed infants. American Academy of Pediatrics Committee on Substance
      Abuse.

PMID- 7630704
TI  - Health supervision for children with neurofibromatosis. American Academy of
      Pediatrics Committee on Genetics.

PMID- 7630705
TI  - Recommendations for preventive pediatric health care. Committee on Practice and
      Ambulatory Medicine.

PMID- 7630706
TI  - Varicella vaccine guidelines.

PMID- 7630707
TI  - Fruit juice.

PMID- 7630708
TI  - HIV/age of first sexual encounter.

PMID- 7630709
TI  - Taste counts!

PMID- 7630710
TI  - Teaching deficit disorder.

PMID- 7630712
TI  - 3-Nitropyrrole and 5-nitroindole as universal bases in primers for DNA sequencing
      and PCR.
AB  - 3-Nitropyrrole and 5-nitroindole have been assessed as universal bases in primers
      for dideoxy DNA sequencing and in the polymerase chain reaction (PCR). In
      contrast to a previous report, we have found that the introduction of more than
      one 3-nitropyrrole residue at dispersed positions into primers significantly
      reduced their efficiency in PCR and sequencing reactions. Primers containing 5
      nitroindole at multiple dispersed positions were similarly affected; for both
      bases only a small number of substitutions were tolerated. In PCR experiments
      neither base, when incorporated into primers in codon third positions, was as
      effective as hypoxanthine, which was incorporated in six codon third positions in
      a 20mer oligomer. However, primers containing up to four consecutive 5
      nitroindole substitutions performed well in both PCR and sequencing reactions.
      Consecutive 3-nitropyrrole substitutions were tolerated, but less well in
      comparable reactions.

PMID- 7630713
TI  - Sse8387I, a useful eight base cutter for mammalian genome analysis (influence of
      methylation on the activity of Sse8387I).
AB  - To develop restriction enzymes that are useful for genome analysis, we previously
      performed screening and isolated Sse8387I from Streptomyces sp. strain 8387.
      Sse8387I is a restriction enzyme that recognizes 5'-CCTGCA/GG-3' and cleaves DNA
      at the site shown by the diagonal (Nucleic Acid Res., 18, 5637-5640). The present
      study evaluated the effects of methylation that is important when Sse8387I is
      used for genome analysis. Sse8387I lost cleavage activity after methylation of
      adenine or methylation of cytosine at any site in the recognition sequence.
      However, the recognition sequence of Sse8387I contains no CG sequence, which is
      the mammalian methylation sequence. In addition, we evaluated the effects of
      methylation of CG at sites other than the recognition sequence. The cleavage
      activity of Sse8387I was maintained even when CG sequences were present
      immediately before or after, or near the recognition sequence, and cytosine was
      methylated. These results suggest that CG methylation does not affect the
      cleavage activity of Sse8387I. Therefore, Sse8387I seems to be very useful for
      mammalian genome analysis.

PMID- 7630714
TI  - Mapping the path of the nascent peptide chain through the 23S RNA in the 50S
      ribosomal subunit.
AB  - Peptides of different lengths encoded by suitable mRNA fragments were
      biosynthesized in situ on Escherichia coli ribosomes. The peptides carried a
      diazirine derivative bound to their N-terminal methionine residue, which was
      photoactivated whilst the peptides were still attached to the ribosome.
      Subsequently, the sites of photo-cross-linking to 23S RNA were analyzed by our
      standard procedures. The N-termini of peptides of increasing length became
      progressively cross-linked to nucleotide 750 (peptides of 6, 9 or 13-15 amino
      acids), to nucleotide 1614 and concomitantly to a second site between nucleotides
      1305 and 1350 (a peptide of 25-26 amino acids), and to nucleotide 91 (a peptide
      of 29-33 amino acids). Previously we had shown that peptides of 1 or 2 amino
      acids were cross-linked to nucleotides 2062, 2506 and 2585 within the peptidyl
      transferase ring, whereas tri-and tetrapeptides were additionally cross-linked to
      nucleotides 2609 and 1781. Taken together, the data demonstrate that the path of
      the nascent peptide chain moves from the peptidyl transferase ring in domain V of
      the 23S RNA to domain IV, then to domain II, then to domain III, and finally to
      domain I. These cross-linking results are correlated with other types of
      topographical data relating to the 50S subunit.

PMID- 7630711
TI  - Compilation and analysis of Bacillus subtilis sigma A-dependent promoter
      sequences: evidence for extended contact between RNA polymerase and upstream
      promoter DNA.
AB  - Sequence analysis of 236 promoters recognized by the Bacillus subtilis sigma A
      RNA polymerase reveals an extended promoter structure. The most highly conserved
      bases include the -35 and -10 hexanucleotide core elements and a TG dinucleotide
      at position -15, -14. In addition, several weakly conserved A and T residues are
      present upstream of the -35 region. Analysis of dinucleotide composition reveals
      A2- and T2-rich sequences in the upstream promoter region (-36 to -70) which are
      phased with the DNA helix: An tracts are common near -43, -54 and -65; Tn tracts
      predominate at the intervening positions. When compared with larger regions of
      the genome, upstream promoter regions have an excess of An and Tn sequences for n
      > 4. These data indicate that an RNA polymerase binding site affects DNA sequence
      as far upstream as -70. This sequence conservation is discussed in light of
      recent evidence that the alpha subunits of the polymerase core bind DNA and that
      the promoter may wrap around RNA polymerase.

PMID- 7630715
TI  - Intrastrand cross-links are not formed in the reaction between transplatin and
      native DNA: relation with the clinical inefficiency of transplatin.
AB  - The reaction between trans-diamminedichloroplatinum(II) and single-stranded
      oligonucleotides containing the sequence d(GXG) (X being an adenine, cytosine or
      thymine residue) yields trans-[Pt(NH3)2[(GXG)-GN7,GN7]] intrastrand cross-links.
      These cross-links do not prevent the pairing of the platinated oligonucleotides
      with their complementary strands but they decrease the thermal stability of the
      duplexes. The thermal stability is not much affected by the chemical nature of
      the X residue and its complementary base. By gel electrophoresis, it is shown
      that the trans- [Pt(NH3)2[d(GTG)-GN7,GN7]] cross-link bends the DNA double helix
      (26 degrees) and unwinds it (45 degrees). The pairing of the platinated
      oligonucleotides with their complementary strands promotes the rearrangement of
      the 1,3-intrastrand cross-links into interstrand cross-links. At a given
      temperature, the nature of the X residue, its complementary base and of the base
      pairs adjacent to the adducts do not dramatically affect the rate of the
      reaction. To know whether trans-[Pt(NH3)2[d(GXG)-GN7,GN7]] cross-links do not
      rearrange in some sequences, the location of these adducts was searched in double
      stranded DNA after reaction with trans-diamminedichloroplatinum(II) by means of
      the 3'-5' exonuclease activity of T4 DNA polymerase. At low level of platination,
      trans-[Pt(NH3)2[d(GXG)-GN7,GN7]] cross-links were not detected. Monofunctional
      adducts and interstrand cross-links were mainly formed. These results are
      discussed in relation with the clinical inefficiency of trans
      diamminedichloroplatinum(II).

PMID- 7630717
TI  - Cooperative assembly of proteins in the ribosomal GTPase centre demonstrated by
      their interactions with mutant 23S rRNAs.
AB  - The ribosomal protein L11 binds to the region of 23S rRNA associated with the
      GTPase-dependent steps of protein synthesis. Nucleotides 1054-1107 within this
      region of the Escherichia coli 23S rRNA gene were mutagenized with bisulphite.
      Twenty point mutations (G-->A and C-->T transitions) and numerous multiple
      mutations were generated. Expression of mutant 23S rRNAs in vivo shows that all
      the mutations detectably alter the phenotype, with effects ranging from a slight
      growth rate reduction to lack of viability. Temperature sensitivity is conferred
      by 1071G-->A and 1092C-->U substitutions. These effects are relieved by point
      mutations at other sites, indicating functional interconnections within the
      higher order structure of this 23S rRNA region. Several mutations prevent direct
      binding of r-protein L11 to 23S rRNA in vitro. These mutations are mainly in a
      short irregular stem (1087-1102) and within a hairpin loop (1068-1072), where the
      protein probably makes nucleotide contacts. Some of these mutations also
      interfere with binding of the r-protein complex L10.(L12)4 to an adjacent site on
      the rRNA. When added together to rRNA, proteins L10.(L12)4 and L11 bind
      cooperatively to overcome the effects of mutations at 1091 and 1099. The proteins
      also stimulate each others binding to rRNA mutated at 1087 or 1092, although in
      these cases binding remains clearly substoichiometric. Surprisingly, none of the
      mutations prevents incorporation of L11 into ribosomes in vivo, indicating that
      other, as yet unidentified, factors are involved in the cooperative assembly
      process.

PMID- 7630716
TI  - Cloning and characterisation of a nuclear, site specific ssDNA binding protein.
AB  - Estradiol inducible, liver-specific expression of the apoVLDL II gene is mediated
      through the estrogen receptor and a variety of other DNA-binding proteins. In the
      present study we report the cloning and characterisation of a single-strand DNA
      binding protein that interacts with the lower strand of a complex regulatory
      site, which includes the major estrogen responsive element and a site that
      resembles the rat albumin site D (apoVLDL II site D). Based on its binding
      specificity determined with electro-mobility shift assays, the protein is named
      single-strand D-box binding factor (ssDBF). Analysis of the deduced 302 amino
      acid sequence revealed that the protein belongs to the heteronuclear
      ribonucleoprotein A/B family (hnRNP A/B) and resembles other known eukaryotic
      single-strand DNA binding proteins. Transient transfection experiments in a
      chicken liver cell-line showed that the protein represses estrogen-induced
      transcription. A protein with similar binding characteristics is present in liver
      nuclear extract. The relevance of the occurrence of this protein to the
      expression of the apoVLDL II gene is discussed.

PMID- 7630718
TI  - Electrophoresis for genotyping: temporal thermal gradient gel electrophoresis for
      profiling of oligonucleotide dissociation.
AB  - Traditional use of an oligonucleotide probe to determine genotype depends on
      perfect base pairing to a single-stranded target which is stable to a higher
      temperature than when imperfect binding occurs due to a mismatch in the target
      sequence. Bound oligonucleotide is detected at a predetermined single temperature
      'snapshot' of the melting profile, allowing the distinction of perfect from
      imperfect base pairing. In heterozygotes, the presence of the alternative
      sequence must be verified with a second oligonucleotide complementary to the
      variant. Here we describe a system of real-time variable temperature
      electrophoresis during which the oligonucleotide dissociates from its target. In
      20% polyacrylamide the target strand has minimal mobility and released
      oligonucleotide migrates extremely quickly so that the 'freed' rather than the
      'bound' is displayed. The full profile of oligonucleotide dissociation during gel
      electrophoresis is represented along the gel track, and a single oligonucleotide
      is sufficient to confirm heterozygosity, since the profile displays two separate
      peaks. Resolution is great, with use of short track lengths enabling analysis of
      dense arrays of samples. Each gel track can contain a different target or
      oligonucleotide and the temperature gradient can accommodate oligonucleotides of
      different melting temperatures. This provides a convenient system to examine the
      interaction of many different oligonucleotides and target sequences
      simultaneously and requires no prior knowledge of the mutant sequence(s) nor of
      oligonucleotide melting temperatures. The application of the technique is
      described for screening of a hotspot for mutations in the LDL receptor gene in
      patients with familial hypercholesterolaemia.

PMID- 7630719
TI  - Double bands in DNA gel electrophoresis caused by bis-intercalating dyes.
AB  - Many bis-intercalating dyes used for fluorescence detection of DNA in
      electrophoresis have been reported to give band-splitting and band-broadening,
      which results in poor resolution and a decreased detection sensitivity. We have
      studied the dimeric dye YOYO-1, and to some extent also TOTO-1 and EthD-1, and
      found that in complex with DNA these dyes give rise to two components with
      different electrophoretic mobilities. Electrophoresis experiments and
      spectroscopic measurements on the two components show that they differ in that
      the DNA molecules have different amounts of dye bound. Our results exclude that
      the extra bands are caused by intermolecular cross-linking. Incubation of the
      samples for increasing times before electrophoresis makes the bands move closer
      and closer to each other as the dye molecules become more homogeneously
      distributed among the DNA molecules. Finally, the two bands merge into one at an
      intermediate position. This equilibration process is extremely slow at room
      temperature (days), and is therefore not a practical method to eliminate band
      splitting in routine analysis. However, we find that if the temperature is raised
      to 50 degrees C, the dye-DNA complexes equilibrate completely in only 2 h.

PMID- 7630720
TI  - Accurate and efficient N-6-adenosine methylation in spliceosomal U6 small nuclear
      RNA by HeLa cell extract in vitro.
AB  - Human U6 small nuclear RNA (U6 snRNA), an abundant snRNA required for splicing of
      pre-mRNAs, contains several post-transcriptional modifications including a single
      m6A (N-6-methyladenosine) at position 43. This A-43 residue is critical for the
      function of U6 snRNA in splicing of pre-mRNAs. Yeast and plant U6 snRNAs also
      contain m6A in the corresponding position showing that this modification is
      evolutionarily conserved. In this study, we show that upon incubation of an
      unmodified U6 RNA with HeLa cell extract, A-43 residue in human U6 snRNA was
      rapidly converted to m6A-43. This conversion was detectable as early as 3 min
      after incubation and was nearly complete in 60 min; no other A residue in U6
      snRNA was converted to m6A. Deletion studies showed that the stem-loop structure
      near the 5' end of U6 snRNA is dispensable for m6A formation; however, the
      integrity of the 3' stem-loop was necessary for efficient m6A formation. These
      data show that a short stretch of primary sequence flanking the methylation site
      is not sufficient for U6 m6A methyltransferase recognition and the enzyme
      probably recognizes secondary and/or tertiary structural features in U6 snRNA.
      The enzyme that catalyzes m6A formation in U6 snRNA appears to be distinct from
      the prolactin mRNA methyltransferase which is also present in HeLa nuclear
      extracts.

PMID- 7630721
TI  - DNA bending in the ternary nucleoprotein complex at the c-fos promoter.
AB  - Transcriptional induction of the c-fos proto-oncogene in response to serum growth
      factors is mediated in part by a ternary complex that forms on the serum response
      element (SRE) within its promoter. This complex consists of Elk-1, serum response
      factor (SRF) and the SRE. Elk-1 is phosphorylated by MAP kinase, which correlates
      with the induction of c-fos transcription. In this study we have investigated the
      protein-induced DNA bending which occurs during the formation and post
      translational modification of the ternary complex that forms at the c-fos SRE.
      Circular permutation analysis demonstrates that the minimal DNA-binding domain of
      SRF, which contains the MADS box, is sufficient to induce flexibility into the
      centre of its binding site within the SRE. Phasing analysis indicates that at
      least part of this flexibility results in the production of a directional bend
      towards the minor groove. The isolated ETS domains from Elk-1 and SAP-1 induce
      neither DNA bending nor increased DNA flexibility. Formation of ternary complexes
      by binding of Elk-1 to the binary SRF:SRE complex results in a change in the
      flexibility of the SRE. Phosphorylation of Elk-1 by MAP kinase (p42/ERK2) induces
      further minor changes in this DNA flexibility. However, phasing analysis reveals
      that the recruitment of Elk-1 to form the ternary complex affects the SRF-induced
      directional DNA bend in the SRE. The potential roles of DNA bending at the c-fos
      SRE are discussed.

PMID- 7630722
TI  - Use of oligonucleotides to define the site of interstrand cross-links induced by
      Adriamycin.
AB  - It has been known for several years that Adriamycin forms adducts and interstrand
      cross-links when reacted for long periods of time with bacterial and mammalian
      DNA in vitro, with the cross-link being restricted to 2 bp elements containing
      GpC sequences. The self-complementary 20mer deoxyoligonucleotide TA4T4GCA4T4A has
      been used in this study as a model of the apparent G-G cross-linking site at GpC
      sequences. The rate of formation of cross-links, as well as the dependence on
      both Adriamycin and Fe(III) concentration, were similar with this oligonucleotide
      as compared with calf thymus DNA. The cross-linking was demonstrated on both
      denaturing and non-denaturing sequencing gels. The half-life of the G-G cross
      link was 40 h, consistent with that implied with high molecular weight,
      heterogeneous sequence DNA. Exonuclease III digests of adducts formed with 20mer
      deoxyoligonucleotides containing single, central G-G, G-I and I-I potential cross
      links revealed that a guanine residue is required at both ends of the cross-link.
      No cross-linking was observed with a similar oligonucleotide containing only a
      single central (G.C) bp.

PMID- 7630723
TI  - Zinc(II) ions selectively interact with DNA sequences present at the TFIIIA
      binding site of the Xenopus 5S-RNA gene.
AB  - It has been known for some time that zinc, as well as most transition metal ions,
      is capable of binding to the DNA bases. However, little is known about the
      presence and distribution of metal binding sites along naturally occurring
      genomic DNA molecules. In this paper, the interaction of zinc with the Xenopus 5S
      RNA gene has been studied and several metal binding sites have been identified on
      the basis of the changes in chemical reactivity observed in the presence of the
      metal. The strongest zinc-binding sites of the Xenopus 5S-RNA gene correspond to
      GGG trinucleotide repeats. Some GG dinucleotides also show a significant affinity
      for zinc. Interestingly, the binding site for TFIIIA, a zinc-finger transcription
      factor, contains several sites with strong zinc affinity. In particular, a TGGGA
      sequence which is essential for the binding of TFIIIA shows the strongest
      affinity for zinc. The conformational properties of this DNA sequence, together
      with the high electronegative potential of GGG runs, is likely to determine its
      strong affinity for zinc. The possible biological relevance of these results is
      discussed.

PMID- 7630724
TI  - Metalloregulation of the cyanobacterial smt locus: identification of SmtB binding
      sites and direct interaction with metals.
AB  - The smtB gene of Synechococcus PCC 7942 encodes a trans-acting repressor of the
      metal-regulated smtA gene that encodes a class II metallothionein. Recombinant
      SmtB has been expressed in Escherichia coli and purified. Electrophoretic
      mobility shift assays using recombinant SmtB or a protein extract from
      Synechococcus PCC 6301 reveal the concentration-dependent formation of three
      specific complexes with the smt operator/promoter. SmtB is also capable of direct
      interaction with metals as evidenced by 65Zn binding to the SmtB protein as well
      as the inhibition of repressor-DNA complex formation in the presence of various
      metal ions. Methylation interference analysis of such complexes identifies four
      protein contact points within the smt operator/promoter DNA. The points of
      contact appear to represent two pairs of binding sites, one pair in each of two
      inverted repeats (nt 548-563, 589-602). The contact points within each pair lie
      on opposing DNA strands and are separated by 10 bp, placing the repressor binding
      sites on opposite sides of the DNA helix. Based on electrophoretic mobility shift
      assays, methylation interference and molecular size calculations we propose that
      recombinant SmtB binds to the smt operator/promoter in multimeric fashion.

PMID- 7630725
TI  - Dual regulation of the Drosophila hsp26 promoter in vitro.
AB  - Efficient heat shock induction of Drosophila hsp26 gene transcription in vivo
      requires binding sites for heat shock factor (HSF) and GAGA factor (GAF) close to
      the TATA box (proximal elements) as well as 350 bp upstream of the start site of
      transcription (distal elements). We have evaluated the contribution of hsp26
      promoter sequences to transcriptional activity in extracts from either heat
      shocked or unstressed fly embryos. Efficient transcription in either extract was
      governed by distinct regulatory principles. Transcription in extracts from
      unstressed embryos relied solely on GAGA elements which efficiently counteracted
      repression by abundant non-specific DNA-binding proteins. Transcription in
      extracts from heat shocked embryos depended only a little on GAGA elements,
      relying mainly on functional HSEs. Constitutively active recombinant HSF or
      native factor in an extract from heat shocked embryos was able to truly activate
      transcription essentially via proximal HSEs, but not when bound to distal sites.
      These two modes of regulation in vitro may correspond to the two functional
      states of the promoter before and after heat shock in vivo.

PMID- 7630727
TI  - Activation of transfer RNA-guanine ribosyltransferase by protein kinase C.
AB  - Transfer RNA-guanine ribosyltransferase (TGRase) irreversibly incorporates
      queuine into the first position in the anticodon of four tRNA isoacceptors. Rat
      brain protein kinase C (PKC) was shown to stimulate rat liver TGRase activity.
      TGRase preparations derived from rat liver have been observed to decrease in
      activity over time in storage at -20 or -70 degrees C. Contamination of the
      samples by phosphatases was indicated by a p-nitrophenylphosphate conversion
      test. The addition of micromolar concentrations of the phosphatase inhibitors
      sodium pyrophosphate and sodium fluoride into TGRase isolation buffers resulted
      in a greater return of TGRase activity than without these inhibitors. Inactive
      TGRase preparations were reactivated to their original activity with the addition
      of PKC. In assays combining both TGRase and PKC enzymes, inhibitors of protein
      kinase C (sphingosine, staurosporine, H-7 and calphostin C) all blocked the
      reactivation of TGRase, whereas activators of protein kinase C (calcium,
      diacylglycerol and phosphatidyl serine) increased the activity of TGRase. None of
      the PKC modulators affected TGRase activity directly. Alkaline phosphatase, when
      added to assays, decreased the activity of TGRase and also blocked the
      reactivation of TGRase with PKC. Denaturing PAGE and autoradiography was
      performed on TGRase isolates that had been labelled with 32P by PKC. The
      resulting strong 60 kDa band (containing the major site for phosphorylation) and
      weak 34.5 kDa band (containing the TGRase activity) are suggested to associate to
      make up a 104 kDa heterodimer that comprises the TGRase enzyme. This was
      corroberated by native and denaturing size-exclusion chromatography. These
      results suggest that PKC-dependent phosphorylation of TGRase is tied to efficient
      enzymatic function and therefore control of the queuine modification of tRNA.

PMID- 7630726
TI  - Involvement of protein kinase C in the control of tRNA modification with queuine
      in HeLa cells.
AB  - The eukaryotic tRNA:guanine transglycosylase (TGT) catalyses the base-for-base
      exchange of guanine for queuine (the q-base)--a nutrition factor for eukaryotes-
      at position 34 of the anticodon of tRNAsGUN (where 'N' represents one of the four
      canonical tRNA nucleosides), yielding the modified tRNA nucleoside queuosine (Q).
      This unique tRNA modification process was investigated in HeLa cells grown under
      either aerobic (21% O2) or hypoxic conditions (7% O2) after addition of
      chemically synthesized q-base to q-deficient cells. While the q-base was always
      inserted into tRNA under aerobic conditions, HeLa cells lost this ability under
      hypoxic conditions, however, only when serum factors became depleted from the
      culture medium. The inability to insert q into tRNA did not result from a lack of
      substrate, because the q-base accumulated within these cells against the
      concentration gradient, suggesting the presence of an active transport system for
      this base in HeLa cells. The activity of the TGT enzyme was restored after
      treatment of the cells with the protein kinase C activator, TPA, even in the
      presence of mRNA or protein synthesis inhibitors. The results indicate that the
      eukaryotic tRNA modifying enzyme, TGT, is a downstream target of activated
      protein kinase C.

PMID- 7630728
TI  - Oligonucleotides containing fluorescent 2'-deoxyisoinosine: solid-phase synthesis
      and duplex stability.
AB  - The fluorescent nucleoside 2'-deoxyisoinosine (2, isoId) has been incorporated
      into oligonucleotides. For this purpose the phosphonate 3a and the
      phosphoramidite 3b, as well as the polymer-linked 3d, have been synthesized and
      oligonucleotides were prepared by P(III) solid-phase chemistry. One or two isoId
      residues were introduced into the oligomer d(T12), replacing dT either in the
      middle or at the 3'- and 5'-ends. The isoId-containing oligomers were hybridized
      with a modified d(A)12 containing the conventional nucleosides (dA, dT, dG and
      dC) opposite to isoId. The replacement of one dT by isoId in the centre of the
      duplex reduced the Tm value by approximately 15 degrees C and a decrease of
      approximately 25 degrees C was found when two isoId residues were incorporated.
      Thermodynamic data were determined from the melting curves. The destabilization
      was almost independent of the four naturally occurring nucleosides located
      opposite to isoId. The isoId (2) seems to be stacked in the duplex when dT-dA
      base pairs are the nearest neighbours; an internal loop is formed in the case of
      oligomers containing two consecutive isold residues.

PMID- 7630729
TI  - Phosphorylation of a chloroplast RNA-binding protein changes its affinity to RNA.
AB  - An RNA-binding protein of 28 kDa (28RNP) was previously isolated from spinach
      chloroplasts and found to be required for 3' end-processing of chloroplast mRNAs.
      The amino acid sequence of 28RNP revealed two approximately 80 amino-acid RNA
      binding domains, as well as an acidic- and glycine-rich amino terminal domain.
      Upon analysis of the RNA-binding properties of the 'native' 28RNP in comparison
      to the recombinant bacterial expressed protein, differences were detected in the
      affinity to some chloroplastic 3' end RNAs. It was suggested that post
      translational modification can modulate the affinity of the 28RNP in the
      chloroplast to different RNAs. In order to determine if phosphorylation accounts
      for this post-translational modification, we examined if the 28RNP is a
      phosphoprotein and if it can serve as a substrate for protein kinases. It was
      found that the 28RNP was phosphorylated when intact chloroplasts were
      metabolically labeled with [32P] orthophosphate, and that recombinant 28RNP
      served as an excellent substrate in vitro for protein kinase isolated from
      spinach chloroplasts or recombinant alpha subunit of maize casein kinase II. The
      28RNP was apparently phosphorylated at one site located in the acidic domain at
      the N-terminus of the protein. Site-directed mutagenesis of the serines in that
      region revealed that the phosphorylation of the protein was eliminated when
      serine number 22 from the N-terminus was changed to tryptophan. RNA-binding
      analysis of the phosphorylated 28RNP revealed that the affinity of the
      phosphorylated protein was reduced approximately 3-4-fold in comparison to the
      non-phosphorylated protein. Therefore, phosphorylation of the 28RNP modulates its
      affinity to RNA and may play a significant role in its biological function in the
      chloroplast.

PMID- 7630730
TI  - The site-specific DNA endonuclease encoded by a group I intron in the
      Chlamydomonas pallidostigmatica chloroplast small subunit rRNA gene introduces a
      single-strand break at low concentrations of Mg2+.
AB  - Two group I introns (CpSSU.1 and CpSSU.2) that each potentially encode a protein
      with two copies of the LAGLI-DADG motif were identified in the Chlamydomonas
      pallidostigmatica chloroplast small subunit rRNA gene. They both belong to
      subgroup IA3 and represent novel insertion positions in this gene (sites 508 and
      793 in the Escherichia coli 16S rRNA). The proteins encoded by the two introns
      were synthesized in vitro and tested for their ability to cleave the homing site
      of their respective introns. Only the CpSSU.1-encoded protein (I-CpaII) was found
      to display specific DNA endonuclease activity. At 0.1 mM MgCl2, I-CpaII nicks
      only the bottom (transcribed) DNA strand, but at concentrations ranging from 0.5
      to 5.0 mM, it cleaves both DNA strands (leaving a 4 nucleotide single-stranded
      extension with 3'-OH overhangs) while preferentially nicking the bottom strand.
      The rate of cleavage of the top strand increases with increasing concentration of
      MgCl2. The preliminary data derived from these endonuclease assays suggest that
      the mode of DNA cleavage by I-CpaII is directed by the availability of Mg2+ and
      the affinity of different binding sites for this cation.

PMID- 7630731
TI  - Disruption of the Crithidia fasciculata RNH1 gene results in the loss of two
      active forms of ribonuclease H.
AB  - Both prokaryotic and eukaryotic cells contain multiple forms of ribonuclease H, a
      ribonuclease that specifically degrades the RNA strand of RNA-DNA hybrids and
      which has been implicated in the processing of initiator RNAs and in the removal
      of RNA primers from Okazaki fragments. The Crithidia fasciculata RNH1 gene
      encodes an RNase H and was shown to be a single-copy gene in this diploid
      trypanosomatid. The RNH1 gene has been disrupted by targeted gene disruption
      using hygromycin or G418 drug-resistance cassettes. Major active forms of RNase H
      (38 and 45 kDa) were observed on activity gels of extracts of wild-type cells or
      cells in which one allele of RNH1 was disrupted. Both the 38 and 45 kDa
      activities were absent in extracts of cells in which both alleles of RNH1 were
      disrupted indicating that both forms of the C.fasciculata RNase H are encoded by
      the RNH1 gene.

PMID- 7630733
TI  - The mobility minima in pulsed-field capillary electrophoresis of large DNA.
AB  - Pulsed-field capillary electrophoresis represents a new tool for rapid and highly
      efficient separations of large biopolymers. The method has been utilized here to
      study dependencies of the electrophoretic mobility upon the frequency and pulse
      shape of applied voltage for large, double-stranded DNA molecules (5-100 kb)
      migrating in neutral polymer solutions. Two different shapes of alternating
      electric field (sine- and square-wave impulses) were examined with the frequency
      values ranging from 1 to 30 Hz. The linear dependence between duration of the
      forward pulse (at which the DNA molecule experiences a minimum mobility) and the
      product N.In(N) (where N is the number of base pairs) was experienced in field
      inversion gel electrophoresis, while exponential dependence was found with the
      sinusoidal electric field. The mobility minima were lower in field-inversion
      electrophoresis than with the biased sinusoidal-field technique. The DNA (5 kb
      concatamers) was adequately separated using a ramp of frequency in the square
      wave electric field, in approximately 1 h. The migration order of DNA fragments
      was referenced through adding a monodisperse DNA (48.5 kb) into the sample. The
      band inversion phenomena were not observed under any experimental conditions used
      in this work.

PMID- 7630732
TI  - Determinants of half-site spacing preferences that distinguish AP-1 and ATF/CREB
      bZIP domains.
AB  - The AP-1 and ATF/CREB families of eukaryotic transcription factors are dimeric
      DNA-binding proteins that contain the bZIP structural motif. The AP-1 and
      ATF/CREB proteins are structurally related and recognize identical half-sites
      (TGAC), but they differ in their requirements for half-site spacing. AP-1
      proteins such as yeast GCN4 preferentially bind to sequences with overlapping
      half-sites, whereas ATF/CREB proteins bind exclusively to sequences with adjacent
      half-sites. Here we investigate the distinctions between AP-1 and ATF/CREB
      proteins by determining the DNA-binding properties of mutant and hybrid proteins.
      First, analysis of GCN4-ATF1 hybrid proteins indicates that a short surface
      spanning the basic and fork regions of the bZIP domain is the major determinant
      of half-site spacing. Replacement of two GCN4 residues on this surface (Ala244
      and Leu247) by their ATF1 counterparts largely converts GCN4 into a protein with
      ATF/CREB specificity. Secondly, analysis of a Fos derivative containing the GCN4
      leucine zipper indicates that Fos represents a novel intermediate between AP-1
      and ATF/CREB proteins. Thirdly, we examine the effects of mutations in the
      invariant arginine residue of GCN4 (Arg243) that contacts the central base
      pair(s) of the target sites. While most mutations abolish DNA binding,
      substitution of a histidine residue results in a GCN4 derivative with ATF/CREB
      binding specificity. These results suggest that the AP-1 and ATF/CREB proteins
      differ in positioning a short surface that includes the invariant arginine and
      that AP-1 proteins may represent a subclass (and perhaps evolutionary offshoot)
      of ATF/CREB proteins that can tolerate overlapping half-sites.

PMID- 7630734
TI  - Correct splicing of a group II intron from a chimeric reporter gene transcript in
      tobacco plastids.
AB  - An in vivo test system was developed to study group II intron splicing in higher
      plant chloroplasts. The chimeric reporter gene uidA was constructed by
      translational fusion of an intron-containing segment of the plastid atpF gene
      with the coding region of a plastid uidA reporter gene. The chimeric uidA gene
      was inserted into the tobacco plastid genome by the biolistic transformation
      procedure using a plastid targeting vector. Correct intron excision was confirmed
      by Northern blot analysis, by sequencing amplified cDNAs and by accumulation of
      the encoded beta-glucuronidase (GUS), the expression of which was dependent on
      intron removal. Removal of the intron from the uidA mRNA is less efficient (<
      50%) than from the atpF mRNA (> 90%). The efficiency of atpF mRNA splicing is not
      affected in the plasmid transformants indicating that inefficient splicing of the
      highly-expressed uidA mRNA is not due to depletion of factor(s) required for the
      atpF intron removal. A derivative of uidA, with a stop codon introduced into the
      loop of domain VI, was also tested. The mutations did not affect the splicing
      efficiency. The chimeric uidA splicing system will facilitate the study of
      structural and sequence requirements for group II intron splicing in plastids of
      higher plants.

PMID- 7630735
TI  - Characterization of three new snRNAs from Saccharomyces cerevisiae: snR34, snR35
      and snR36.
AB  - Genes for three novel snRNAs of Saccharomyces cerevisiae have been isolated,
      sequenced and tested for essentiality. The RNAs encoded by these genes are
      designated snR34, snR35 and snR36 respectively and contain 203, 204 and 182
      nucleotides. Each RNA is derived from a single copy gene and all three RNAs are
      believed to be nucleolar, i.e. snoRNAs, based on extraction properties and
      association with fibrillarin. SnR34 and snR35 contain a trimethylguanosine cap,
      but this feature is absent from snR36. The novel RNAs lack elements conserved
      among several other snoRNAs, including box C, box D and long sequence
      complementarities with rRNA. Genetic disruption analyses showed each of the RNAs
      to be dispensable and a haploid strain lacking all three RNAs and a previously
      characterized fourth snoRNA (snR33) is also viable. No differences in the levels
      of precursors or mature rRNAs were apparent in the four gene knock-out strain.
      Possible roles for the new RNAs in ribosome biogenesis are discussed.

PMID- 7630737
TI  - Screening of phage display immunoglobulin libraries by anti-M13 ELISA and whole
      phage PCR.

PMID- 7630736
TI  - Xenopus sonic hedgehog as a potential morphogen during embryogenesis and thyroid
      hormone-dependent metamorphosis.
AB  - The hedgehog family of proteins have been implicated as important signaling
      molecules in establishing cell positional information and tissue patterning. Here
      we present the cloning and characterization of a hedgehog homologue from Xenopus
      laevis similar to the sonic class of vertebrate hedgehog genes. We isolated
      Xenopus hedgehog (Xhh) from a subtractive hybridization screen designed to
      identify genes induced by thyroid hormone during metamorphosis of the X.laevis
      gastrointestinal tract. In the intestine, Xhh mRNA expression was up-regulated at
      the climax of metamorphosis (stage 62) when intestinal epithelium underwent
      morphogenesis. Treatment of pre-metamorphic tadpoles with exogenous thyroid
      hormone (TH) resulted in a similar pattern of Xhh induction. Furthermore, TH
      induction was resistant to inhibitors of protein synthesis suggesting that Xhh is
      a direct thyroid hormone response gene. The expression and TH regulation of Xhh
      was not limited to the intestine, but was also observed in the limb and a mixture
      of pancreas and stomach. Throughout development, Xhh mRNA was present at varying
      levels with the earliest expression being detected at neurula stage. The highest
      levels of Xhh were observed between stages 33 and 40 shortly before tadpole
      feeding begins. Whole mount in situ hybridization analysis of Xhh expression in
      pre-hatching, stage 32 tadpoles demonstrated staining in the notochord and floor
      plate similar to that observed for other vertebrate hedgehog genes. Together,
      these data suggest a putative role for Xhh in organ development during both
      amphibian embryogenesis and metamorphosis.

PMID- 7630738
TI  - A novel and simple methodology to generate subtracted cDNA libraries.

PMID- 7630739
TI  - Attenuation of PCR inhibition in the presence of plant compounds by addition of
      BLOTTO.

PMID- 7630740
TI  - A rapid one-tube genomic DNA extraction process for PCR and RAPD analyses.

PMID- 7630741
TI  - Somatostatin receptor expression in the thyroid demonstrated with 111In
      octreotide scintigraphy.
AB  - Neuroendocrine tumors with somatostatin receptor expression may be localized by
      111In-octreotide scintigraphy. This study examines those thyroid conditions where
      111In-octreotide uptake could be observed also in the thyroid gland. 26
      consecutive patients who underwent 111In-octreotide scintigraphy for tumor
      localization were additionally examined for thyroid disease by sonography and
      99mTc-pertechnetate scintigraphy. 12 of these patients had no significant thyroid
      uptake and had an euthyroid normal-sized thyroid gland 14 patients with 111In
      thyroid uptakes had endemic goiters, two of them with thyroid autonomy and one
      with Graves' disease. Thus, 111In-octreotide thyroid uptake was predominantly
      seen in patients with endemic goiter with or without thyroid autonomy.

PMID- 7630742
TI  - [Diagnosis of SDAT by HMPAO SPECT and vitamin B12 serum concentration].
AB  - It is quite difficult to confirm the diagnosis of demential disorders, including
      senile dementia of the Alzheimer type (SDAT) by clinical means only. Through the
      combination of 99mTc-HMPAO brain SPECT and serum vitamin B12 determination it was
      hoped to speed up and improve the diagnosis of SDAT. 116 patients who had been
      divided into four groups according to their defect pattern in the 99mTc-HMPAO
      brain SPECT 17 very probably had SDAT; of these 15 showed a defect-pattern with
      brain SPECT which could be associated to SDAT. The majority of SDAT patients had
      serum vitamin B12 levels in the lower normal range or pathologically below that
      range. Both investigations contributed to establishing the SDAT diagnosis without
      replacing other investigations. The determination of serum vitamin B12 does not
      require any major additional effort.

PMID- 7630743
TI  - [Skeletal scintigraphy in the treatment planning for hemimandibular elongation].
AB  - Hemimandibular elongation is characterized by unilateral continuous growth of the
      mandibular ramus and condyle. Skeletal scintigraphy is indicated for the
      assessment of prospective growth. When growth has ceased a correcting osteotomy
      may be performed. In the case of severe active growth and fast progressive facial
      asymmetry the growth centre should be removed surgically by condylectomy. 21
      patients with facial asymmetry and/or laterognathia underwent skeletal
      scintigraphy. 19 patients showed symmetrical or nearly symmetrical nuclear
      uptake. In 11 cases a correcting osteotomy was performed without any relapse. 2
      patients showed markedly unilateral increased nuclear uptake. One of them
      underwent condylectomy and showed a stable result 3 years postoperatively. The
      other patient underwent a correcting osteotomy with subsequent recurrence of
      laterognathia. By visualization of the pathophysiological process skeletal
      scintigraphy yields information for treatment planning in hemimandibular
      elongation.

PMID- 7630744
TI  - [191mIr: distribution and retention in animal experiments].
AB  - Ultrashort-lived tracer 191mIr (T1/2 = 4.92 s) can be obtained with a high yield
      from an 191Os/191mIr generator with a low 191Os breakthrough. It was eluated
      directly into the tail veins of Wistar rats. These animals were imaged
      dynamically (five frames/s) up to 40 s. The measurement was repeated five times
      on each animal. The whole-body retention and biodistribution of 191Os was studied
      by sacrificing the rats at one and four days, respectively, after injection. The
      activity retained was highest in the kidneys and the spleen, followed by the
      muscles and the liver. These values indicate that the breakthrough is by no means
      dangerous and that investigations can be repeated immediately with a radiation
      exposure of no significance. Furthermore, all investigations in the same animal
      were reproducible, suggesting that 191mIr might be a good tracer for nuclear
      angiograms.

PMID- 7630745
TI  - [Potential and limitation of myocardial perfusion scintigraphy for detection of
      viability].
AB  - Scintigraphic detection of myocardial viability is required for treatment
      planning and prognostication in patients with contractile dysfunction. There are
      four pathophysiological entities of dysfunction in coronary artery disease; one
      of them, "hibernating" myocardium, cannot be differentiated from scar or necrosis
      by mere perfusion imaging. Due to the determinants of delayed activity
      distribution after 201Tl injection, optimized imaging protocols using this tracer
      allow for adequate differentiation in many instants. Differentiation between
      "stunned" and "hibernating" myocardium or scar is achieved with all perfusion
      indicators actually available. Though 201Tl imaging with optimized protocols is
      almost as efficacious in viability detection as 18F-FDG positron emission
      tomography, the latter actually remains the reference method particularly in
      patients with severe left ventricular dysfunction at coronary occlusions.

PMID- 7630746
TI  - [18FDG in the primary staging of lung tumors. Results with a gamma camera and a
      511 keV collimator].
AB  - The diagnosis of primary lung tumors requires a precise staging according to the
      TNM classification. In contrast to established imaging methods 18FDG describes
      the functional metabolic processes in the tumor tissue due to increased
      glycolysis. This paper describes the use of 18FDG in the primary staging of lung
      tumors and metastases. 44 patients were studied with a gamma camera and a 511 keV
      collimator. In comparison to pulmonary tumors and metastases detected by other
      imaging methods (107) the accumulation of 18FDG has a sensitivity of 85%, in
      lesions verified by histology (50) of 89%, in primary tumors (35) of 100% and in
      metastases (63) of 76%. As an alternative to FDG PET studies, primary staging of
      lung tumors is possible with a gamma camera, suitable for ECT and fitted with a
      511 keV collimator.

PMID- 7630747
TI  - [MRI and oncoscintigraphy with 99m-Tc-MIBI in the follow up of thyroid cancer].
AB  - Magnetic resonance imaging (MRI) and 99mTc-MIBI oncoscintigraphy are new
      procedures for the detection of recurrent differentiated thyroid cancer. We
      evaluated the utility of both techniques compared to ultrasonography, radioiodine
      scanning, and measurement of serum thyroglobulin in patients with (n = 21) or
      without suspicion (n = 34) of tumor relapse. Although MRI was most effective in
      detecting local recurrencies (sensitivity: 100%), additional diagnostic
      information was only obtained in patients with mediastinal lesions. On the other
      hand, oncoscintigraphy was less sensitive (67%) but highly specific in
      differentiating reactive lymph node enlargement from metastatic disease
      (specificity: 93.5%). Oncoscintigraphy may be used instead of radioiodine
      scanning in patients with doubtful lymph node findings and spare them withdrawal
      of TSH-suppressive hormone medication. Routine estimation of serum thyroglobulin
      proved to be highly efficient in screening for tumor relapse using a cut-off
      level of 3 ng/ml (accuracy: 100%).

PMID- 7630748
TI  - Immunogenic and non-immunogenic hyperthyroidism. Recent trends in prealpine
      Switzerland and in coastal Poland.
AB  - Annual occurrences of immunogenic (IH) and non-immunogenic hyperthyroidism (NIH)
      between Berne (1976, 1982, 1991) and Szczecin (1973, 1980, 1991) were compared.
      Out of 21,025 patients referred for thyroid examinations, 10.1% (average) were
      hyperthyroid. In Berne (former endemic goiter region) and Szczecin (without
      goiter endemicity) IH occurred in 41% and 68%, NIH in 59% and 32% of hyperthyroid
      patients, respectively. Within a stable incidence of NIH in Berne, toxic adenomas
      (TA) decreased from 41% (1976) to 17% (1991) (p < 0.005). In Szczecin, where
      iodine deficiency is in an early stage, the TA frequency did not change
      significantly: from 24% (1973) to 28% (1991). Increases of TA or of multifocal
      functional autonomy apparently "mark" incipient or, respectively, decreasing
      deficiencies in nutritious iodine. Hyperthyroid patients in Berne compared to
      Szczecin were older, both with IH (54 versus 45 y) and NIH (65 versus 52 y). Age
      at diagnosis was stable in Berne but increasing (p < 0.05) in Szczecin (from 43
      to 52 y).

PMID- 7630749
TI  - Professional development. Chronic cardiac disease: revision notes (continuing
      education credit).

PMID- 7630750
TI  - Troubleshooters.

PMID- 7630751
TI  - Starring role.

PMID- 7630752
TI  - Barriers to protection.

PMID- 7630753
TI  - Serious mental health problems: policy changes.
AB  - Recent developments in services and strategies for helping people with serious
      mental health problems represent a watershed in mental health provision. This has
      implications not only for specialist mental health nursing, but also-- as
      increasing numbers of people with serious mental health problems live in the
      community-- for nurses working in all areas of health care, who will have to play
      a role in meeting their needs. This article describes current developments in
      policy and practice, and seeks to explain the basic principles of working with
      people in this client group.

PMID- 7630754
TI  - New facts on schizophrenia.
AB  - Recent research using brain imaging and molecular biological methods has
      clarified our knowledge about the cause of schizophrenia. The picture emerging is
      of a group of illnesses with their origins in neurodevelopmental abnormalities.
      The most severe forms of schizophrenia are accompanied by defects in memory and
      attention. There are several implications of this new knowledge for nursing. Our
      current nursing models are less than adequate and represent outdated and
      discredited theory. Additionally we must consider new ways of working with people
      who have what are essentially brain diseases. However, it is also clear that
      social and psychological factors are crucial in determining outcome and quality
      of life for people with schizophrenia and their families. The Thorn Programme,
      which trains nurses in case management and various psychosocial interventions,
      exemplifies the way forward for mental health nursing and such developments will
      secure a place for the profession in the services of the future.

PMID- 7630755
TI  - Durkheim, social integration and suicide rates.
AB  - This second paper of six on the application of sociology in health care considers
      the work of Emile Durkheim. He was concerned with the production of social order
      through relationships and shared values. Durkheim conceived social phenomena as
      'social facts' which could be studied, and his treatment of suicide as a case
      study of social fact is discussed here. His work on the processes of social
      cohesion has influenced the work of sociologists up to the present day.

PMID- 7630756
TI  - Using Orem's model in the care of adolescents.
AB  - Nursing care for hospitalised adolescents should be based on a thorough knowledge
      of their normal development while supporting and maintaining healthy growth,
      despite the impact of a disruptive illness. Care for adolescents should be
      achieved through partnership, taking into account their views and opinions,
      offering support and guidance as well as care. Adolescents have the right to be
      involved in decisions about all aspects of their care. This article explores the
      benefits of Orem's model of nursing in the care of this group

PMID- 7630757
TI  - Topical and systemic treatment of psoriasis: Part 2.
AB  - The second of two papers on the subject describes a range of treatments for
      psoriasis. The pharmaceutical treatment of the condition is described together
      with consideration of the general support of the person affected. Treatment may
      be topical or systemic depending on the severity of the condition

PMID- 7630758
TI  - Arthritis: healing touch?

PMID- 7630760
TI  - Men's health: vital signs.

PMID- 7630759
TI  - Stress: Cracking points.

PMID- 7630761
TI  - Work Well Campaign. Health at work.

PMID- 7630762
TI  - International perspective. A change for the better.

PMID- 7630763
TI  - Peril of the stiff upper lip.

PMID- 7630764
TI  - Skin care: sun protection.

PMID- 7630765
TI  - Professional development. Skin conditions: knowledge for practice (continuing
      education credit).

PMID- 7630767
TI  - Tweaking the market.

PMID- 7630768
TI  - Shifting focus. Interview by David Payne.

PMID- 7630766
TI  - From cradle to grave.

PMID- 7630769
TI  - Moribund or mutating?

PMID- 7630770
TI  - Quality and quantity: staffing and skill mix in neonatal care.
AB  - The delivery of front-line care in an acute sector of the health care system, the
      neonatal service, was the focus for a large-scale investigation. The aim was to
      carry out a major study that could inform policy and identify possible
      improvements in practice and organisation in the context of concerns about stress
      in neonatal nursing, staffing levels, skill mix and training. Fifty-six neonatal
      units and more than 700 nurses participated. Large inter-units differences were
      found and in many neonatal units the staffing levels and qualification in
      specialty rates were found to be lower than those recommended. The implementation
      of the findings are discussed and recommendations made.

PMID- 7630771
TI  - Child health. Negotiating care roles.
AB  - This paper examines the use of research findings related to the negotiation of
      care roles between paediatric nurses and the parents of children in hospital. The
      implications for future practice are discussed.

PMID- 7630772
TI  - Making sense of ... pain management.
AB  - Pain is a common human fear. A sound knowledge of the nature of pain should
      inform nursing practice. This paper outlines basic pain physiology related to
      practical issues of pain management.

PMID- 7630773
TI  - Subcutaneous administration of adrenaline for anaphylaxis.
AB  - Seventeen children who have had life-threatening anaphylaxis and who are treated
      in one clinic are all attending mainstream schooling and carry adrenaline. This
      paper looks at the education of their teachers in emergency procedures.

PMID- 7630774
TI  - Supporting the patient with inflammatory bowel disease.
AB  - Inflammatory bowel disease is a term that describes Crohn's disease, colitis and
      proctitis. This paper considers the nurse's role in patient education,
      information and support for people with these conditions.

PMID- 7630775
TI  - For good measure.

PMID- 7630776
TI  - International perspective. Gulf of Mexico.

PMID- 7630777
TI  - Who was ... Huntington?

PMID- 7630778
TI  - Breathless.

PMID- 7630779
TI  - Handling aids: lifting and moving patients.

PMID- 7630780
TI  - Stand and deliver.

PMID- 7630782
TI  - Students. Find a common ground.

PMID- 7630781
TI  - Students. Walking into a war zone.

PMID- 7630783
TI  - Students. Survival kit.

PMID- 7630784
TI  - Professional development: skin conditions. The role of the nurse.

PMID- 7630785
TI  - From Project 2000 to the job market.

PMID- 7630787
TI  - Midwives' big break.

PMID- 7630786
TI  - Shallow standards.

PMID- 7630788
TI  - The ministry without fun.

PMID- 7630789
TI  - Training with tiers.

PMID- 7630790
TI  - Discharge to the community of older patients from hospital.
AB  - Current trends in health-care delivery have led to significant changes in
      hospital discharge programmes in Britain with particular reference to older
      people. This state of affairs has prompted debate between those who are accusing
      hospitals of discharging patients rather too early and those who welcome early
      discharge in the light of the philosophy of primary nursing. The plight of older
      people leaving hospital has been a subject of considerable study over the past
      two decades. This paper examines the latest advances in the debate

PMID- 7630791
TI  - An assessment of procedures.
AB  - Seven in-patients, who had the insertion of a dynamic hip screw, were included in
      a small study. They were discharged from the orthopaedic nursing development unit
      at the Royal Victoria Infirmary, Tyneside, over a two-month period. The nursing
      records were assessed before discharge to show the planning stages in hospital.
      The respondents were interviewed two weeks after discharge to determine the
      effectiveness of the hospital intervention. The main issues that arose were a
      need for more discussion with patients and the lack of information provided.

PMID- 7630792
TI  - Growth hormone and prolactin.

PMID- 7630793
TI  - Supervision registers and mental health problems.
AB  - This paper considers the implications of the introduction of supervision
      registers for people with severe mental illnesses. It discusses concerns
      expressed by the medical profession and mental health charities. Nurses'
      reticence in entering the debate is noted as well as how supervision registers
      are interpreted in practice and the potential problems or benefits of the policy.
      The impact of power relationships in psychiatry are discussed in the light of the
      introduction of supervision registers. Finally, the implications for future
      practice and health-care delivery systems are highlighted.

PMID- 7630794
TI  - How men and women view the world: a sexual perspective.
AB  - This papers presents a number of views on men and women and how they react to one
      another. Very little attention is given to discussing gender issues within nurse
      education, despite the fact that understanding gender perspectives would have a
      great impact on nursing care. As the majority of nurses are women and offer a
      different perspective on life from men, the authors find this issue needs to be
      addressed at pre- and post-registration levels.

PMID- 7630795
TI  - Democratic health care.

PMID- 7630796
TI  - Prepared for a smooth recovery?

PMID- 7630797
TI  - Recognising risk factors.

PMID- 7630798
TI  - Living with childhood cancer.

PMID- 7630799
TI  - Not for resuscitation.

PMID- 7630800
TI  - Changing for the better?

PMID- 7630801
TI  - Education under fire.

PMID- 7630802
TI  - Direction uncertain?

PMID- 7630803
TI  - Bottling up the pressure.

PMID- 7630804
TI  - Mental health tribunals need re-evaluation.

PMID- 7630805
TI  - Life-giving fatwa.

PMID- 7630806
TI  - Positive mental attitude.

PMID- 7630807
TI  - Letter from France.

PMID- 7630808
TI  - Promising start.

PMID- 7630809
TI  - A serious loss of blood.

PMID- 7630810
TI  - The role of managed care in overcoming fragmentation.
AB  - The fragmentation of patient care remains an issue despite the NHS
      reorganisation. Models of managed care that encompass all providers present an
      opportunity for pulling the strands together.

PMID- 7630811
TI  - Clinical protocols and the law.

PMID- 7630813
TI  - Great expectations.

PMID- 7630812
TI  - Key terms in managed care.

PMID- 7630814
TI  - Easing the pressure for hip fracture patients.

PMID- 7630815
TI  - Weber, authority and the organisation of health care.
AB  - The third paper in the series on sociology discusses the work of Max Weber. It
      traces the origins and main themes of his work. The parallels between his work
      and contemporary issues in the organisation of health care are outlined, in
      particular, the insights provided into bureaucracy and authority.

PMID- 7630816
TI  - Analysis of advice given to patients after hysterectomy.

PMID- 7630817
TI  - The healing touch.

PMID- 7630818
TI  - Distant voices.

PMID- 7630819
TI  - Coping.

PMID- 7630820
TI  - No mixed sex, please.

PMID- 7630821
TI  - Days of confusion.

PMID- 7630822
TI  - Evaluating cord care.

PMID- 7630823
TI  - Preventable damage.

PMID- 7630824
TI  - Professional development: skin conditions. Revision notes.

PMID- 7630825
TI  - Clinical health promotion and family physicians.

PMID- 7630826
TI  - Emotions and health in occupational life: new scientific findings and policy
      implications.
AB  - A large number of patients suffer from cardiovascular (CV) risk and disease.
      While many of them have experienced chronic emotional distress at work or at home
      as a subjectively important risk factor, clinical medicine has so far often
      disregarded the role of emotional distress in the pathogenesis of CV disease.
      However, new findings show striking associations. This paper summarizes the
      evidence from 3 epidemiologic studies on work-related distress and CV risk in
      middle-aged male populations. The empirical work is based on a theoretical model
      termed effort-reward imbalance. Workers who exhibit high effort in combination
      with low reward, and especially with low job security or promotion prospects,
      suffer from a 3- to 4-fold increased risk of CV disease, and they exhibit higher
      blood pressure, blood lipids and fibrinogen. Implications of these findings for
      prevention and intervention are discussed.

PMID- 7630827
TI  - Exploring information-exchange in consultation: the patients' view of performance
      and outcomes.
AB  - Many prescriptions for the 'ideal' consultation highlight the need for
      discussion, information and explanation as adjuncts to the task of diagnosis and
      treatment. While there is evidence for the importance of these activities in
      terms of patient satisfaction, there has been no empirical test of their specific
      performance in practice, nor of an association between these activities and a
      range of other outcomes. The present study explores these issues in the context
      of Frederikson's information-exchange model of medical consultation, using the
      concept of information-exchange tasks as process variables. Results show that the
      information-exchange tasks are important to patients, and doctor performance on
      the tasks provides a good predictor of satisfaction. In addition, it is shown
      that the immediate outcome measures of patient understanding, the developing
      doctor-patient relationship, the patient's view of the appropriateness of
      treatment, and the perceptions of the doctor's response are each related to a
      particular sub-set of information-exchange activities. It is concluded that
      attending to the concepts, perceptions and views of the patient offers a more
      effective strategy for consultation management than a focus on providing vast
      amounts of standardized information.

PMID- 7630828
TI  - Health promotion and clinical dialogue.
AB  - Clinical medicine would gain from a discussion of the significance of health
      promotion. Some central concepts are discussed: the diagnostic process; disease
      prevention vs. health promotion; the practical importance of the understanding of
      the difference between the 2 concepts health and absence-of-disease. The concept
      of health catches the intra-personal level, the undisrupted self, whereas absence
      of disease concerns the proper functioning of the organism, the human biology. By
      means of comparing 2 diagnoses, multiple sclerosis (MS) and fibromyalgia syndrome
      (FS), it is argued that there are diagnoses of at least 2 distinct kinds. The
      diagnosis of MS is similar to a scientific discovery, whereas the diagnosis of FS
      is constructed more like criminal law. Consequently, diagnosis-based disease
      prevention and health promotion have to comply with a wide range of reality.
      Finally, clinical dialogue is pointed out as a method that successfully combines
      diagnostic, preventive and promotive efforts, as well as clinical care and cure.

PMID- 7630829
TI  - How do GPs discuss subjects other than illness? Formulating and evaluating a
      theoretical model to explain successful and less successful approaches to
      discussing psychosocial issues.
AB  - A theoretical model was formed, according to grounded theory, to understand how
      discussions about psychosocial problems might be designed. It was used in 19
      videotaped consultations where it was considered relevant for the physician to
      take up psychosocial issues. 'Concern' i.e. that the patient could express that
      which was most pressing, was used as an indicator of outcome. A uniform pattern
      was observed in those cases where the patients expressed 'concern', in that the
      physician encouraged the patient by using open-ended questions, by following up
      the information received, and by having an empathic approach. On the other hand,
      in consultations where 'concern' was not expressed, it was noticed that the
      physician often asked close-ended, leading or negative questions, thus putting an
      end to the dialogue and, as a consequence, to the follow-up phase. Important
      therapeutic skills would appear to be the ability to reassure and support the
      patient as well as to be able to explain the connection between the patient's
      symptoms and psychosocial problems, rather than to solve these problems.

PMID- 7630830
TI  - The role of Dutch general practitioners in clinical health promotion.
AB  - In this contribution it is argued that Dutch general practitioners (GPs) must
      make the transition from simply giving information to their patients, to
      providing them with medical education. Dutch GPs are in a prime position to
      contribute to the aims of health promotion. Instead of focusing health promotion
      on prevention, they should primarily promote the health of their patients,
      especially these patients with a chronic disease. In order to provide proper care
      for their disabled patients, they have to limit the time they spend on caring for
      people suffering from minor ailments. Again, this aim cannot be achieved by
      simply providing information. The patients have to overcome their reluctance to
      change their consultation behaviour, but the GPs also have to change their
      attitude by adopting new skills in order to influence their patients in this
      respect.

PMID- 7630831
TI  - Clinical health promotion and family physicians: a Canadian perspective.
AB  - Many attempts have been made recently in North America to increase the activities
      of physicians in clinical prevention and health promotion. This article reviews:
      (1) the development of guidelines by both the Canadian Task Force on the Periodic
      Health Examination and the U.S. Preventive Services Task Force; (2) attempts at
      dissemination and implementation; (3) definitions of health promotion concepts,
      including clinical health promotion; (4) factors facilitating and limiting the
      incorporation of clinical prevention and health promotion into family practice;
      and (5) principles of learning and behavior change which can assist family
      physicians to practise clinical health promotion. Family physicians are best
      advised to focus on facilitating behavior change with their own patients,
      utilizing a triage strategy to determine which patients to target.

PMID- 7630832
TI  - Patient use of a computer for prevention in primary care practice.
AB  - A computerized health information system for prevention can provide an efficient
      way to enhance the doctor-patient interaction and provide patient-specific
      education materials. A computer system called HealthTouch was developed by family
      physicians and placed in 29 randomly selected primary care practices in Virginia
      for 1 year. Data were collected from three sources: randomly selected patients'
      charts, the HealthTouch data base, and patient telephone interviews. Data from
      these sources were combined, and frequency distributions and comparisons of
      responses by demographic attributes were analyzed using the chi-square statistic.
      During the study year, 9799 adult patients used the HealthTouch system.
      HealthTouch users were younger, on average, than the overall patient population,
      and the majority (89%) were either very satisfied or satisfied with the system.
      Computers are effective tools to collect, organize, and store patient information
      about prevention.

PMID- 7630833
TI  - Health promotion in primary health care: the situation in England.
AB  - National policy, including changes to the management of the National Health
      Service, is intended to increase the amount of primary and secondary prevention
      in primary health care in England. The growth of financial power of general
      practitioners makes them key decision-makers in planning and delivering health
      promotion. The vast majority of people in contact with their family doctor could
      benefit from making appropriate lifestyle modifications. However, the level and
      quality of health promotion activity in primary care is variable, with many
      patients not receiving interventions. A review of research indicates that both
      skepticism about the relationship between behaviour and risk factor, and lack of
      confidence in efficacy of health promotion in changing patient behaviour act as
      barriers to general practitioners taking on more health promotion activity. For
      prevention work to increase, therefore, general practitioners require more
      evidence of effective replicable interventions, and appropriate training on the
      design and implementation of programmes. The role of the Health Education
      Authority, the national agency for health promotion in England, in meeting these
      needs is described. The paper also includes a brief discussion of evaluation
      methods for assessing the success of health promotion interventions.

PMID- 7630834
TI  - The role of the general practitioner in health promotion in the UK: the case of
      coronary heart disease prevention.
AB  - This paper examines the approach taken to health promotion and disease prevention
      in primary care in the UK, using coronary heart disease prevention (CHD) as an
      illustration. The paper considers the approach taken by the UK's government, the
      level of involvement of general practitioners (GP) and community nurses in CHD
      prevention, the factors that influence variation in involvement and the evidence
      for effectiveness.

PMID- 7630835
TI  - Preventive care in general practice in Australia: a public health perspective.
AB  - There is considerable potential in Australia for implementing effective
      preventive care strategies in the general practice setting, especially in the
      context of Australia's new health goals and targets towards the year 2000. There
      is a clear need for the clinical paradigm, which focuses on developing
      efficacious, intensive, practitioner-delivered lifestyle change interventions, to
      be integrated within a broader public health approach. However, while there has
      been considerable growth in the breath and variety of health promotion research
      and activity being carried out in general practice in Australia, the evidence
      supportive of the efficacy and effectiveness of physician-based interventions
      (except in the case of smoking cessation) has been less than compelling, and a
      number of problems still remain. These include: health promotion still remains a
      minor component of the great majority of consultations; there are many potential
      interventions which are possible, but little evidence that they will be used
      appropriately; there is little evidence that patients who are most in need are
      receiving appropriate services; there is generally a poor linkage between
      research and practice; and there are real doubts about the ability of the system
      to sustain preventive care in general practice.

PMID- 7630836
TI  - Difference of lifestyle advice between traditional Chinese medical doctors
      (TCMDs) and Western-style medical doctors (WSMDs) in People's Republic of China.
AB  - The role of physicians in providing lifestyle advice is very important in disease
      prevention and health promotion. This study was designed to examine (a) the
      difference of lifestyle advice provided for general practice patients between
      traditional Chinese medical doctors (TCMDs) and Western-style medical doctors
      (WSMDs), (b) the difference of lifestyle advice provided for cardiovascular
      disease (CVD) patients between the TCMDs and WSMDs, (c) the difference of
      lifestyle advice provided for general practice and CVD patients by the TCMDs, and
      (d) the difference of lifestyle advice provided for general practice and CVD
      patients by the WSMDs. One thousand four-hundred and thirty general practice
      patient records and 640 CVD patient records from a Western-style medical
      hospital, and 1620 general practice records and 830 CVD patient records from a
      traditional Chinese medical hospital were selected for comparison. Results
      indicated that TCMDs were more likely to provide nutrition, exercise, and stress
      management for their patients than WSMDs. On the other hand, WSMDs were more
      likely to provide smoking and alcohol consumption for their patients than the
      TCMDs. In addition, both TCMDs and WSMDs were more likely to provide all
      categories of lifestyle advice for their CVD patients than their general practice
      patients.

PMID- 7630837
TI  - Strengths and weaknesses in health counseling in Finnish primary health care.
AB  - Representative samples of Finnish health centres and of their physicians, nurses
      and physiotherapists were selected for a comprehensive survey on the
      professionals' work characteristics, health education attitudes and counseling
      practices. The main objectives of the study were to study the degree of
      implementation of patient counseling, with special reference to the national
      goals in health policy and to analyze the determinants of counseling practices in
      terms of predisposing, enabling and reinforcing factors. Broadly defined patient
      counseling was frequent in the contacts with all 3 professional groups and no
      differences in counseling frequency were found between different sizes of health
      centres. However, the objective of implementing counseling in every patient
      contact, with the incorporation of guidance regarding healthy living habits in
      it, recommended in the national health policy goals, was only partially realized.
      There were distinct differences between the 3 professional groups in counseling
      attitudes, topics, methods and purposes. These differences reflect, to a great
      extent, the differences in the professional tasks and the basic training between
      the 3 groups and also differences in the characteristics of patient contacts.
      These findings indicate a need for further in-service training in the methods of
      patients counseling, as well as restructuring the health care delivery system to
      allow more time for counseling, better continuity between contacts and more co
      work between the members of primary care teams.

PMID- 7630838
TI  - Patient education for low back pain in general practice.
AB  - This comparative study of patient and general practitioner perceptions of patient
      education for low back pain (LBP) revealed significant differences in
      perspective. It suggests that although some general practitioners recognise the
      importance of patient education, they blame patients for its assumed failure as a
      management strategy. The patients in this study identified a range of reasons
      which explain their difficulties in following prevention advice which relate to
      not only limitations in themselves, but also to broader contextual factors over
      which they have little control. It is argued that both the inadequacy of current
      professional assumptions and the contextual factors that influence patients'
      prevention behaviours need to be acknowledged as a first step towards improving
      patient education for LBP in general practice.

PMID- 7630839
TI  - Thyroiditis. A disease with many faces.
AB  - Inflammatory conditions of the thyroid are commonly encountered in clinical
      practice. Older and middle-aged women are most often affected, and the clinical
      course may be acute, subacute, or chronic. Differentiating the various forms of
      thyroiditis can be difficult, because they often mimic other disease processes
      and each other. Diagnosis requires an awareness of the distinguishing
      characteristics of each type of thyroiditis as well as the overlapping features.

PMID- 7630840
TI  - Preparticipation sports examinations. Efficient risk assessment in children and
      adolescents.
AB  - Whether preparticipation sports examinations are necessary and what they should
      include are matters of debate, especially in the young because of the low yield
      of new medical diagnoses. The goal of the examining physician is to determine
      whether the athlete is mentally, developmentally, and physically capable of
      safely competing in recreational and competitive sports. We recommend that
      examinations precede the start of an activity by 4 to 6 weeks and be done every 3
      years. History taking should include parental input and a private interview with
      the athlete when possible. The specific areas of the body to be used in a
      particular sport should be emphasized in the physical examination, and the amount
      of contact and energy required should be considered. Abnormal findings should be
      thoroughly evaluated to rule out risk of injury or sudden death before approval
      to participate is granted.

PMID- 7630841
TI  - Antibiotic prophylaxis for medical and dental procedures. A look at AHA
      guidelines and controversial issues.
AB  - Are prophylactic antibiotics really needed to prevent endocarditis and prosthetic
      joint infection when patients at risk undergo medical and dental procedures
      likely to cause bacteremia? Although animal studies seem to support such
      prophylaxis, clinical trials in humans are lacking, and some authorities believe
      it is unethical to give antibiotics without more evidence of benefit. Dr Uyemura
      examines the problem in this article.

PMID- 7630842
TI  - Fancy lures, fishing lines, and quality patient care.

PMID- 7630843
TI  - Giardiasis. Taming this pervasive parasitic infection.
AB  - Parasitic infection due to Giardia lamblia can produce severe, disabling
      gastrointestinal symptoms. Outbreaks have been linked to contaminated municipal
      water supplies and situations involving person-to-person contact.
      Immunocompromised patients are especially at risk. Because microscopic
      examination of stool detects the parasite in only about half of infected
      patients, use of enzyme-linked immunosorbent assay to detect Giardia-specific
      antigen is becoming increasingly popular. In most patients, therapy with
      quinacrine (Atabrine) hydrochloride, metronidazole (Flagyl, Protostat), or a
      combination of the two is effective.

PMID- 7630844
TI  - Allergic drug reactions. How to minimize the risks.
AB  - Assessment of patients in whom an allergic drug reaction is suspected should
      include a carefully taken drug history. This should be followed by diagnostic
      testing if it is available for the drug in question. If neither an alternative
      therapeutic agent nor a diagnostic test is available, then a provocation
      challenge or desensitization may be necessary. Increased understanding of
      allergic drug reactions requires the following: better pharmacoepidemiologic
      studies, improved in vitro and in vivo methods of studying the immune responses
      involved, and expanded comparisons between the pharmacokinetics and
      pharmacodynamic effects of drugs and their metabolites. Until improvements are
      made in these areas, the appropriate approach is to avoid the unnecessary use of
      drugs. When a drug is required, patient risk factors for an allergic reaction
      must always be weighed against the benefits of treatment.

PMID- 7630845
TI  - Is your patient using cocaine? Clinical signs that should raise suspicion.
AB  - Cocaine use often has profound effects on the body. Medical complications that
      may be seen in users include headache, sexual dysfunction, violent behavior,
      chronic cough, seizures, and myocardial infarction. The type of cocaine used and
      the method of use often determine the kind of problems that occur. Patients may
      be reluctant or unable to offer information about their drug use during
      evaluation, so awareness of the medical consequences of cocaine use and a high
      index of suspicion are essential.

PMID- 7630846
TI  - Niacin for lipid disorders. Indications, effectiveness, and safety.
AB  - Niacin can be very effective and safe in lowering low-density lipoprotein
      cholesterol and triglyceride levels and also in increasing high-density
      lipoprotein cholesterol levels. In combination with other lipid-lowering drugs
      (eg, bile acid sequestrants), it has reduced the incidence of cardiovascular
      events and stopped the progression of coronary artery lesions. It may be the most
      cost-effective lipid-lowering agent currently available. At lower doses,
      sustained-release forms of niacin may also improve patient compliance.

PMID- 7630847
TI  - When to worry about headache. Head pain as a clue to intracranial disease.
AB  - Careful evaluation of headache is important to detect potentially morbid but
      treatable causes. Although such causes represent only 10% of all emergency
      department visits for headache, the consequences of a missed diagnosis can be
      severe. Unfortunately, the cost of performing computed tomography or magnetic
      resonance imaging for every patient with headache is prohibitive. However,
      familiarity with the differential diagnostic considerations, together with a high
      index of suspicion, should allow physicians to perform efficient, cost-effective
      examinations of all patients who seek treatment for headache.

PMID- 7630848
TI  - Endoscopic evaluation of iron deficiency anemia. A guide to diagnostic strategy
      in older patients.
AB  - Gastrointestinal blood loss is the primary cause of iron deficiency anemia in
      older adults. Bidirectional endoscopy (combined colonoscopy and
      esophagogastroduodenoscopy) is highly sensitive and specific in its ability to
      locate gastro-intestinal lesions resulting in iron deficiency anemia. Although
      the diagnostic yield of esophagogastroduodenoscopy is higher than that of
      colonoscopy, the possibility of malignant disease dictates that initial
      colonoscopy be performed in all but a few cases involving distinct upper
      gastrointestinal risk factors and symptoms. If neither colonoscopy nor
      esophagogastroduodenoscopy identifies a source of blood loss, a safe course is to
      observe the patient and provide supplemental iron. Patients who fail to respond
      to supplemental iron or who become transfusion-dependent require further
      evaluation. Small-bowel evaluation has a role in selected patients.

PMID- 7630849
TI  - 'Pap' psychology.

PMID- 7630850
TI  - How common is iron overload?

PMID- 7630851
TI  - Neuroleptic treatment in the elderly.

PMID- 7630852
TI  - Thyroid screening. How to interpret and apply the results.
AB  - The ultrasensitive third-generation assay for thyrotropin (TSH) is now the "gold
      standard" for measuring thyroid activity. Who should be screened with it, and
      what further studies should be done if results are abnormal? Which patients with
      subclinical disease should receive treatment? Drs Brody and Reichard discuss
      these and other issues and provide an algorithm for thyroid screening.

PMID- 7630853
TI  - Solitary thyroid nodules. Separating benign from malignant conditions.
AB  - Although features found on history taking, physical examination, thyroid function
      tests, and imaging studies help categorize solitary thyroid nodules as benign or
      malignant, fine-needle aspiration biopsy is the diagnostic test of choice.
      Nodules found to be malignant on cytologic examination should be treated with
      surgery. Benign nodules may be followed clinically or treated with levothyroxine
      to suppress their growth. Intermediate nodules should be excised if there is
      clinical suspicion of malignancy. In suspect nodules, levothyroxine therapy with
      follow-up ultrasound assessment for size is appropriate. Nodules that do not
      shrink significantly within 6 months should be excised.

PMID- 7630854
TI  - New antiepileptic drugs.
AB  - Notwithstanding pharmacokinetics has greatly increased the rational approach to
      the drug treatment of epilepsies, about 25% of the patients do not respond to the
      therapy. Therefore, a great effort has been made to discover new antiepileptic
      drugs effective in refractory seizures. On the basis of increased knowledge of
      seizure pathophysiology two principal groups of drugs have been developed: the
      first enhancing brain GABA activity (vigabatrin); the second inhibiting
      excitatory amino-acids (lamotrigine and felbamate). Oxcarbazepine has the same
      mechanism of action as carbamazepine, whereas gabapentin's mechanism is still
      uncertain. The major clinical indications of these new antiepileptic drugs are
      represented by partial complex seizures. Side effects (mostly regarding the
      central nervous system) appear mild, and clinical interactions have little
      importance. The role of therapeutic drug monitoring for these substances is at
      present not well established.

PMID- 7630855
TI  - Receptor-mediated pathways of endothelium activity in experimental
      atherosclerosis.
AB  - The pharmacological characterization of endothelial receptor activity during the
      progression of atherosclerosis in Watanabe heritable hyperlipidemic (WHHL)
      rabbits was examined. The data presented show that progression of atherosclerosis
      affects endothelial receptor functionality in different ways. Nucleotide receptor
      activity is preserved for longer than that of the other endothelial receptors,
      i.e. muscarinic- and P2y-purinoceptors. This difference means that, in WHHL
      rabbit aorta, some mechanisms proposed to explain impaired endothelium-mediated
      relaxation in atherosclerosis must be excluded. It is therefore hypothesized that
      atherosclerosis in genetically hyperlipidemic animals selectively influences the
      receptorial arrangement of endothelium, as in other published examples of
      selective remodeling of receptors in arteries. Endothelial cell receptors may
      become a new interesting target for the development of drugs to treat
      atherosclerosis.

PMID- 7630856
TI  - Brain electrobiogenesis protection induced by nimodipine and MK-801 during acute
      hypoxia in hypertensive rats.
AB  - The protective effect of nimodipine, a calcium entry blocker, and MK-801, an
      excitatory amino acid antagonist, on the cortical electrobiogenesis of
      hypertensive SHR-Charles-River adult rats during a 90-s session of acute hypoxia,
      was tested either with a single treatment or with a therapeutic association.
      Pretreatment with nimodipine alone (0.1 mg kg-1, i.v.) was particularly effective
      in increasing the rat brain resistence to hypoxia when compared to the controls.
      MK-801 pretreatment alone (3 mg kg-1, subcutaneous), improved significantly the
      recovery of brain electrical activity from hypoxia, as it not only shortened the
      recovery time but also abolished the post-hypoxic burst activity. The combined
      pretreatment with both drugs, using the same doses, displayed a more powerful
      brain protective effect on the cortical electrobiogenesis than the single drug
      pretreatment, suggesting the existence of a synergy between nimodipine and MK
      801.

PMID- 7630857
TI  - Effect of Vaccinium myrtillus anthocyanosides on ischaemia reperfusion injury in
      hamster cheek pouch microcirculation.
AB  - The effects of Vaccinium myrtillus anthocyanosides (VMA) on ischaemia reperfusion
      injury were investigated in the hamster cheek pouch microcirculation. Ischaemia
      was induced by clamping the cheek pouch for 30 min followed by 30 min of
      reperfusion. The microvasculature was visualized by a fluorescence technique. VMA
      [10 mg (100 g body weight)-1] were orally administered for 2 and 4 weeks. The
      number of adhering leukocytes to venular vessel walls, the perfused capillary
      length, the increase in permeability, the arteriolar diameter changes were
      determined. Ischaemia and reperfusion were associated with increased number of
      leukocytes sticking to venules, decreased number of perfused capillaries, and
      increased permeability. VMA decreased the number of leukocytes sticking to the
      venular wall and preserved the capillary perfusion; the increase in permeability
      was significantly reduced after reperfusion. VMA saved the arteriolar tone and
      induced the appearance of rhythmic diameter changes of arterioles. These results
      demonstrate the ability of Vaccinium myrtillus anthocyanosides to reduce
      microvascular impairments due to ischaemia reperfusion injury, with preservation
      of endothelium, attenuation of leukocyte adhesion and improvement of capillary
      perfusion.

PMID- 7630858
TI  - Combined action of inhibitors of polyamine biosynthetic pathway with a known
      antimalarial drug chloroquine on Plasmodium falciparum.
AB  - Difluoromethylornithine (alpha-DFMO), a specific enzyme activated inhibitor of
      ornithine decarboxylase activity, a bis (benzyl) polyamine analogue (MDL 27695)
      and chloroquine resulted in a dose-dependent inhibition of the parasite. The IC50
      value of alpha-DFMO, MDL 27695 and chloroquine was 1.85 mM, 2.0 microM and 23 ng
      ml-1 respectively. The combined action of MDL 27695 (3 microM) and chloroquine (5
      ng ml-1) on P. falciparum growth showed near additive effect, whereas the
      combination of alpha-DFMO (1.0 mM) and chloroquine (5 ng ml-1) was more than the
      effect of each drug individually but not additive. Similarly the combined effect
      of MDL 27695 (3 microM) and alpha-DFMO (1.0 mM) on P. falciparum growth was not
      additive. The effect of these inhibitors alone and in combination on polyamine
      biosynthesis is also reported.

PMID- 7630859
TI  - Discrimination of transport systems for methylmercury-cysteine uptake in rat
      erythrocytes by inhibitors and other factors.
AB  - The transport systems for methylmercury-cysteine (MeHgCys) uptake by isolated
      erythrocytes from rats were studied at 5 degrees C. Probenecid was used to test
      the organic acid transport system at different concentrations. While inhibiting
      the organic acid transport system by probenecid (0.25 mM), the following agents
      were used to determine other transport systems for MeHgCys uptake: (1) ouabain
      and sodium fluoride (NaF) were used to test the active transport system; (2) 4,4'
      diisothiocyano-2,2'-stilbenendisulphonic acid (DIDS) and N-ethylmaleimide (NEM)
      were used to test the C1-ion transort system; (3) colchicine and vinblastine were
      used t o test the microtubule system; (4) hexanol was used to test the protein
      mediated trasport systems and the non-electrolyte diffusion; (5) valinomycin was
      used to test the effect of the membrane potential on MeHgCys uptake. Furthermore,
      the effects of NH4+, Li+ and Na+ in the buffer on MeHgCys uptake were examined
      with or without probenecid. The results showed that most of MeHgCys was
      transported by the organic acid transport system. Colchicine and vinblastine
      stimulated MeHgCys uptake. NH4+, Li+ and Na+ ions could stimulate MeHgCys uptake
      with or without probenecid. Meanwhile, a small amount of MeHgCys was transported
      by means of the non-electrolyte diffusion which was stimulated by hexanol.
      Furthermore, DIDS could stimulate MeHgCys uptake and the transport systems for
      MeHgCys uptake were sensitive to the membrane potential.

PMID- 7630860
TI  - Improvement of ursodeoxycholic acid bioavailability by 2-hydroxypropyl-beta
      cyclodextrin complexation in healthy volunteers.
AB  - Tablets containing the inclusion complex of ursodeoxycholic acid (UDCA) with 2
      hydroxypropyl-beta-cyclodextrin were prepared by direct compression. Plasma
      concentrations of UDCA were determined in six healthy volunteers after oral
      administration of tablets containing the inclusion complex or UDCA alone
      (Ursacol). Following the administration of the complex tablets, the mean area
      under the plasma concentration curve (AUC) and the maximum UDCA plasma
      concentration (Cmax) were significantly higher than those obtained after the
      administration of the commercial ones. Moreover, the time of maximum plasma
      concentration (tmax) appeared at a shorter time. These results may be explained
      by the increase of the UDCA dissolution rate via complex formation.

PMID- 7630861
TI  - Inhibition of L-carnitine uptake into primary rat cortical cell cultures by GABA
      and GABA uptake blockers.
AB  - L-carnitine plays a central role in mitochondrial function and is found to be
      differentially distributed in the brain. We have shown before that the uptake of
      L-carnitine into cultured rat cortical neurones was temperature-dependent, as
      well as potently inhibited by factors affecting the sodium gradient as well as by
      molecules resembling its structure, e.g. D-carnitine, acetyl-L-carnitine and
      gamma-aminobutyric acid (GABA). GABA was the most potent inhibitor of L-carnitine
      uptake. In the present study we have found that specific GABA uptake blockers,
      nipecotic acid, cis-4-hydroxynipecotic (HNA), guvacine, 2,4-diaminobutyric acid
      (DABA) and NO 711 inhibit L-carnitine uptake even more potently than GABA.
      However, apart from NO 711, they caused about the same maximal inhibition, 67.4%
      at 50 microM for guvacine, compared to 60.5% by GABA. NO 711 was extremely potent
      and blocked 80.5% of the L-carnitine uptake. In contrast, the GABAA receptor
      agonists, isonipecotic acid and isoguvacine, or the antagonist bicuculline, at
      similar concentrations (50 microM), did not significantly inhibit the uptake of
      the L-carnitine. However, bicuculline at relatively high concentration (500
      microM) was inhibitory (38%). The GABAB receptor agonist, baclofen, or
      antagonist, phaclofen, were ineffective, although 5-aminovaleric acid did
      significantly inhibit uptake at both 50 and 500 microM, causing 22 and 48%
      inhibition respectively. Like bicuculline, it was not as effective as GABA or the
      specific GABA uptake blockers. The results indicate that the uptake of L
      carnitine by rat cortical neurones occurs in part by a process that can be
      potently inhibited by GABA and GABA uptake blockers.

PMID- 7630862
TI  - The pathophysiology of ischaemic preconditioning.

PMID- 7630863
TI  - Pronounced antiarrhythmic effects of ischaemic preconditioning--are there
      possibilities for pharmacological exploitation?

PMID- 7630864
TI  - Particular outcomes of myocardial ischaemia: stunning and hibernation.
AB  - There are several potential outcomes of myocardial ischaemia. When ischaemia is
      severe and prolonged, irreversible damage occurs and there is no recovery of
      contractile function. When myocardial ischaemia is less severe but still
      prolonged, myocytes may remain viable but exhibit depressed contractile function.
      Under these conditions, reperfusion restores complete contractile performance.
      This type of ischaemia, leading to a reversible, chronic left ventricular
      dysfunction, has been termed hibernating myocardium. The difference between this
      condition and that described before, i.e. prolonged ischaemia, which results in
      further damage on reperfusion, is, most likely, related to residual coronary
      flow. In the hibernating myocardium, which is supplied by a narrow coronary
      artery, blood flow is not low enough to cause progression toward tissue necrosis,
      but it is low enough to cause intracellular changes and adaptative mechanisms
      which, in turn, are responsible for the down-regulation of myocardial
      contractility and for the preservation of viability. The level of underperfusion
      is sufficient to maintain aerobic metabolism of the quiescent myocardium as
      demonstrated by the absence of lactate and creatine phosphokinase releases. There
      are no doubts that revascularization is essential for hibernating myocardium, and
      the clinical goal to achieve is the possibility of accurately distinguishing
      viable from infarcted tissue. A third possible outcome of myocardial ischaemia is
      a post-ischaemic ventricular dysfunction or myocardial stunning. This term
      describes a transient mechanical dysfunction that persists on reperfusion after a
      short period of ischaemia, despite the absence of irreversible damage.

PMID- 7630865
TI  - Cellular electrophysiological aspects of myocardial protection.
AB  - Oxygen radicals (OR) generated at the time of reflow of the ischaemic myocardium
      may cause 'reperfusion injury'. To protect myocardium from this injury, it is
      important to understand how OR cause their deleterious effects on myocytes. Here
      we describe the basic electrophysiological alterations caused by OR in patch
      clamped ventricular myocytes isolated from the rat heart. Oxygen radicals
      generated by dihydroxyfumarate (DHF) caused a lengthening of action potential
      duration (APD) and the appearance of arrhythmogenic alterations such as early and
      delayed afterdepolarizations. Prolongation of APD was accompanied by a reduction
      in calcium and potassium currents. When intracellular calcium levels were kept
      constantly low by 500 microM EGTA in the pipette solution, the effects of DHF on
      action potential duration and the occurrence of early afterdepolarizations were
      largely prevented. It is concluded that exposure to OR may induce
      electrophysiological alterations in isolated myocytes. They are related to
      changes in specific ionic currents and in levels of intracellular calcium.

PMID- 7630866
TI  - Recent developments in the use of calcium antagonists in myocardial protection.
AB  - For more than two decades calcium antagonists (CEBs) have been widely used for
      the treatment of myocardial ischaemia (angina pectoris). Amongst the classes of
      CEBs, the 1,4-dihydropyridines (DHPs), like nifedipine, have been used for this
      indication because of their haemodynamic and electrophysiological properties. The
      ability of nifedipine to reduce afterload and to induce coronary vasodilation, as
      well as to increase collateral blood supply, has supported its extensive use in
      the treatment of angina pectoris. However, its short duration of action also
      provokes reflex tachycardia, which often limits its beneficial effect and may
      actually precipitate pain. The newer DHPs, such as amlodipine and lacidipine, are
      endowed with slow onset and long duration of vasodilatory activity; they are able
      to reduce coronary resistance with little or no effect on heart rate. The more
      lipophilic DHP, lacidipine, shows also a pronounced vascular protection, on both
      smooth muscle and endothelium, and is able to reduce the formation of atheroma
      plaque in animal models at therapeutic doses. This protective activity might be
      explained in terms of both the effective CEB activity of lacidipine together with
      antioxidant properties that this DHP has shown.

PMID- 7630867
TI  - [Mechanical assistance of circulation. 42 cases].
AB  - OBJECTIVES: Mechanical circulatory support was proposed in patients in
      cardiogenic shock, as a bridge to cardiac transplantation or weaning. The aim of
      the present study is an analysis of the first 42 cases. METHODS: The 42 cases
      included 31 patients in cardiogenic shock unresponsive to medical therapy, good
      cardiac transplant candidates, and 11 patients unweanable off ventricular assist,
      or in shock in the intensive care unit. Results are evaluated in terms of
      transplantability and hospital survival. RESULTS: Overall success rate is 67%,
      ranging from 25% in previously transplanted patients to 46% following acute
      myocardial infarction and 57% in cardiomyopathy. Age and learning curve played a
      significative role. CONCLUSION: These data suggest that mechanical support
      improves survival in patients in cardiogenic shock. Earlier implantation should
      improve the patient outcome.

PMID- 7630868
TI  - [Assay of products of fibrin and fibrinogen degradation in disseminated
      intravascular coagulations. Evaluation of a new technique].
AB  - OBJECTIVES: An increase in fibrin or fibrinogen degradation products (FDP) is
      highly indicative of the diagnosis of disseminated intravascular coagulation
      (DIC). We assessed the sensitivity and specificity of a recently developed method
      (FDP plasma) with respect to other classical methods. METHODS: FDP plasma was
      compared to another semi-quantitative method using monoclonal antibodies (D-di
      test), a semi-quantitative method on serum using polyclonal antibodies (Spli
      prest) and a quantitative ELISA (D-dimer). The results from 34 patients with DIC
      were compared with those of several control groups (30 healthy volunteers, 34
      women at the end of an uneventful pregnancy, and 24 of them after delivery), in
      order to assess sensitivity and specificity of each test. RESULTS: The 3 plasma
      tests using monoclonal antibodies demonstrated similar sensitivities (88-100%),
      which was clearly higher than the sensitivity of serum test, using polyclonal
      antibodies. Specificity was identical (97-98%) for the 3 semi-quantitative tests
      when normal ranges were defined according to the results of the control groups.
      It was higher than the sensitivity of the ELISA test. CONCLUSION: Due to their
      higher specificity, and to their rapidity, FDP semi-quantitative tests are the
      most suitable tests for the diagnosis of DIC. Spli-prest, which showed a low
      sensitivity, should be replaced by D-di test or FDP-plasma, which displayed
      similar good results.

PMID- 7630869
TI  - [Vaccination against hepatitis B virus. Value of intradermal administration in
      dialysed patients non responsive to intramuscular approach].
AB  - OBJECTIVES: Approximately 16-27% of dialysis patients (DP) have no detectable
      antibodies after 5 intramuscular injections of hepatitis B vaccine and represent
      a group at high risk to contract hepatitis B virus. We report the efficacy of the
      intradermal route of a recombinant hepatitis B vaccine (r-HBV) in non-responsive
      dialysis patients in our dialysis unit. METHODS: Intradermal vaccinations were
      performed in 20 dialysis patients (mean age 62 years) non-responsive to the
      intramuscular injections (mean 6.8). Five micrograms of r-HBV (Engerix B, SK and
      F) were administered intradermally every two weeks (maximum 70 micrograms) until
      a level of anti-HBV antibodies (anti-HBs) arbitrarily choosen of > or = 230
      mUI/ml was attained. Anti-HBs was determined after the fourth and subsequent
      intradermal injections (IMX, Abbott). RESULTS: Fourteen dialysis patients (70%)
      developed anti-HBs > 10 mUI/ml (geometric mean titers of 330 mIU/ml). Among
      these, 9 developed seroprotective levels before the fifth injection. Five
      patients developed anti-HBs > or = 1000 mUI/ml and 6 others developed anti-HBs >
      or = 230 mUI/ml. After the intradermal injections were discontinued, 11 patients
      were monthly monitored for at least 3 months, and 6 for one year. The geometric
      mean antibody level was at 3 months: 157 (n = 11), at 6 months: 122 (n = 8), at
      nine months: 117 (n = 6), and at 12 months: 66 mIU/ml (n = 6). The age and the
      sex, haemodialysis duration, albumin levels or treatment by erythropoietin did
      not seem to play a role in appearance of anti-HBs. CONCLUSIONS: Our experience in
      20 dialysis patients shows that repeated low-dose intradermal injections resulted
      in long-term seroprotection in a substantial number of dialysis patients non
      responsive to the intramuscular vaccinations.

PMID- 7630870
TI  - [Pancytopenia resolved by the treatment of hyperthyroidism].
AB  - Hyperthyroidism can be associated with various haematological disorders related
      to several mechanisms. These disorders might be related to the reduced life-span
      of whole blood components and/or to an autoimmune mechanism. Only one case of
      pancytopenia has yet been reported. The observation of 3 new personal cases (1
      toxic adenoma and 2 Graves' disease) led us to review the pathogeny of
      haematological disorders found in hyperthyroidism. Only one patient had
      antineutrophil autoantibodies. Direct and indirect Coomb's test, and Dixon's test
      were negative. In all patients, bone marrow aspiration was unable to demonstrate
      pernicious anaemia or myelodysplastic syndrome. Two patients presented
      cytological signs of macrophage activation with eosinophilia. These cytological
      features were compatible with an immuno-allergy mechanism. All haematological
      disorders disappeared when patients became euthyroid. In all cases, the
      haematological abnormalities were quite mild and might have gone unnoticed. Thus,
      it can be suggested that the frequency of pancytopenia in hyperthyroidism is
      underestimated.

PMID- 7630871
TI  - [Hysteroscopic cure under ultrasonic control of complex and/or recurrent uterine
      synechiae].
AB  - Hysteroscopy now plays a major role in the rapidly changing therapeutic approach
      to the diagnosis and treatment of uterine synechiae. The fibrous nature of the
      lesion and its precise localization can be determined. Operative hysteroscopy has
      greatly benefited from technological progress in optic fibers and
      instrumentation. It is now possible to control the endocavitary operation with a
      video-endoscope. In this report, we present preliminary results obtained in 11
      patients who underwent echo-controlled hysteroscopic surgical cure of complex
      and/or recurrent uterine synechiae. The intra-operative echographic control was
      validated in the operating theatre radiographically. Intra-operative echography
      allowed hysteroscopic lysis of intrauterine adhesions at a controlled and
      equivalent distance from the uterine walls. It is thus possible to better treat
      the uterine cornua since the operator is informed when to limit progression to
      avoid massive fluid infusion into the abdominal cavity and perforation of the
      uterus. With this technique we obtained 8 normal cavities with bilateral tube
      permeability. Normal cycles were achieved in 10 patients. The effect of this
      newly developed technique on improving fertility cannot yet be established.

PMID- 7630872
TI  - [Computed tomography in thoracic pathology].
AB  - The fundamental principles of computed tomography (CT), its clinical applications
      and costs are presented followed by the indications and results in diseases of
      the mediastinum, the oesophagus, heart and great vessels, and the lung and
      pleura. The CT scan can give the precise localization and density of mediastinal
      tumours and be used to distinguish thymomas, goiters, lymph nodes, lymphomas,
      neurinomas and different bronchogenic and pleuropericardial cystic formations.
      The operability of oesophageal cancer can also be determined. In cardiovascular
      diseases, the CT scan is particularly useful to identify inborn anomalies,
      aneurysms, aortic dissection or caval compression or thrombus formation. In lung
      diseases, the indications for a CT scan are particularly important in
      bronchopulmonary cancer, tuberculosis, bronchopathies and chronic lung diseases.
      In bronchogenic cancer, for example, the CT scan is not only a major diagnostic
      tool but is also particularly useful in determining the prognosis and for
      following the effectiveness of treatment. The CT scan can be used to identify
      both effusions of liquid and gas as well as pleural reactions producing thick
      membranes of importance for both aetiology and later follow-up. Bronchectasis can
      be identified on serial sections where the degree of extension can be measured.
      CT scan is also indicated in patients with emphysema, both for evaluating
      extension and follow-up. Finally the indications and contraindications for
      interventional computed tomography, particularly in guiding needle biopsies, is
      presented.

PMID- 7630873
TI  - [Ischemic cerebral vascular accident with simultaneous acute alcoholic
      intoxication in a young subject].

PMID- 7630874
TI  - [Pulmonary endocarditis complicated by extracapillary glomerulonephritis].

PMID- 7630875
TI  - [Heparin-fluindione relay. Comparison of 2 prescription models].

PMID- 7630876
TI  - [Mycobacterium tuberculosis resists to cold!].

PMID- 7630877
TI  - [An unique brain metastasis revealing rectal adenocarcinoma].

PMID- 7630878
TI  - [Apropos of the transmission of hepatitis C virus].

PMID- 7630879
TI  - A new approach to the evaluation of protein secondary structure predictions at
      the level of the elements of secondary structure.
AB  - For many purposes, such as the prediction of the class of protein folds, the
      existence of an element of secondary structure rather than its precise position
      and length must be defined correctly. However, most methods for the evaluation of
      secondary structure prediction consider success in terms of the percentage of
      individual amino acids predicted correctly. In this paper the success in
      predicting elements of secondary structure is discussed. The number of
      overlapping residues in the predicted and observed secondary structures were
      considered as a function of the total number of amino acids in the observed and
      predicted secondary structures. A matrix search procedure was used to remove the
      ambiguity which similar studies may have had in defining the equivalent secondary
      structures between predicted and observed structures. In this study a loop was
      treated in the same way as an alpha-helix and a beta-strand. To describe the
      accuracy at the level of elements of secondary structure, a set of parameters was
      defined, similar to those used commonly at the level of individual amino acids.
      This approach was used to assess the methods of Chou and Fasman (1974b,
      Biochemistry, 13, 222-245), Lim (1974b, J. Mol. Biol., 88, 873-894) and Garnier
      et al. (1978, J. Mol. Biol., 120, 97-120). It was found that these methods were
      much poorer at the secondary structure level than at the amino acid level. This
      approach can be used generally for secondary structure prediction methods.

PMID- 7630880
TI  - Solvent interactions with pi ring systems in proteins.
AB  - The interaction of water molecules with apolar amino acids is an important aspect
      of the hydrophobic effect and hence of protein folding. Our distributed multiple
      electrostatic model for water interacting with phenylalanine dipeptides shows
      that minimum energy sites exist above the aromatic ring such that a solvent
      molecule can interact with the pi electrons, but only when this site is not
      blocked by main-chain atoms or disturbed by main-chain polar atoms. This is
      consistent with the experimental evidence of others that water can hydrogen bond
      to aromatic pi electrons. In contrast, our analysis of solvent interactions with
      phenylalanine residues based on 48 high-resolution, well-refined protein
      structures shows that the dominant interaction of solvent molecules is with the
      edge of the ring and not with the pi elections. As the faces of phenylalanine
      rings tend to be buried, and solvent interactions with neighbouring polar atoms
      are more favourable, the interaction of water molecules with the faces of
      aromatic pi rings appears not to occur frequently in proteins.

PMID- 7630881
TI  - Homology modelling of the Lactococcus lactis leader peptidase NisP and its
      interaction with the precursor of the lantibiotic nisin.
AB  - A model is presented for the 3-D structure of the catalytic domain of the
      putative leader peptidase NisP of Lactococcus lactis, and the interaction with
      its specific substrate, the precursor of the lantibiotic nisin. This homology
      model is based on the crystal structures of subtilisin BPN' and thermitase in
      complex with the inhibitor eglin. Predictions are made of the general protein
      fold, inserted loops, Ca2+ binding sites, aromatic interactions and electrostatic
      interactions of NisP. Cleavage of the leader peptide from precursor nisin by NisP
      is the last step in maturation of nisin. A detailed prediction of the substrate
      binding site attempts to explain the basis of specificity of NisP for precursor
      nisin. Specific acidic residues in the S1 subsite of the substrate binding region
      of NisP appear to be of particular importance for electrostatic interaction with
      the P1 Arg residue of precursor nisin after which cleavage occurs. The
      hydrophobic S4 subsite of NisP may also contribute to substrate binding as it
      does in subtilisins. Predictions of enzyme-substrate interaction were tested by
      protein engineering of precursor nisin and determining susceptibility of mutant
      precursors to cleavage by NisP. An unusual property of NisP predicted from this
      catalytic domain model is a surface patch near the substrate binding region which
      is extremely rich in aromatic residues.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7630882
TI  - LIGPLOT: a program to generate schematic diagrams of protein-ligand interactions.
AB  - The LIGPLOT program automatically generates schematic 2-D representations of
      protein-ligand complexes from standard Protein Data Bank file input. The output
      is a colour, or black-and-white, PostScript file giving a simple and informative
      representation of the intermolecular interactions and their strengths, including
      hydrogen bonds, hydrophobic interactions and atom accessibilities. The program is
      completely general for any ligand and can also be used to show other types of
      interaction in proteins and nucleic acids. It was designed to facilitate the
      rapid inspection of many enzyme complexes, but has found many other applications.

PMID- 7630883
TI  - A theoretical study of substrate-induced activation of dienelactone hydrolase.
AB  - Dienelactone hydrolase (DLH), an enzyme from the beta-ketoadipate pathway,
      catalyses the hydrolysis of dienelactone to maleylacetate. DLH is unusual because
      it is the only known naturally occurring enzyme which contains the catalytic
      triad Cys ... His ... Asp. This triad has previously been created artificially in
      the mutant serine proteases, thiol subtilisin and thiol trypsin. In both cases
      the mutant enzymes exhibited activities several orders of magnitude lower than
      the wild type enzymes; the low reactivity has generally been attributed to the
      inability of these enzymes to form a catalytically active thiolate anion (Cys-
      ... His+ ... Asp-). The crystal structure of DLH suggests that the native enzyme
      exists predominantly in a catalytically inert configuration; the triad cysteine
      is neutral and points away from the active site binding cleft. However, a
      crystallographic analysis of C123S DLH complexed with an isostructural inhibitor
      (dienelactam) indicates that substrate binding induces a prototropic
      rearrangement of the active site prior to catalysis which results in the
      formation of a highly nucleophilic thiolate anion. We have performed ab initio
      SCF/MP2 calculations on a relatively small portion of the active site of DLH to
      examine the details of this activation process. Our calculations provide
      supporting evidence that the conformational changes observed in the crystal
      structure due to inhibitor (or substrate) binding facilitate the formation of a
      reactive thiolate anion. In particular, substrate binding alters the position of
      Glu36; the carboxylate side chain of Glu36 is pushed towards C123 enabling it to
      abstract the thiol proton thus creating a catalytically active thiolate
      anion.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7630884
TI  - Biased random mutagenesis of peptides: determination of mutation frequency by
      computer simulation.
AB  - Cassette mutagenesis is a method of protein engineering which generates a wide
      diversity of genetic variants that can be subjected to either selection or
      screening. As long as the target sequence to be modified is kept short
      (corresponding to four to six amino acids), complete combinatorial libraries can
      be produced. A major problem arises when longer peptides are to be engineered for
      desired functions. In such situations the production of a limited collection of
      variants can be helpful; thus, biased random mutagenesis and 'doping schemes'
      have been reported previously. Here we describe a computer algorithm that enables
      the determination of the degree of phosphoramidite contamination of nucleotide
      precursor reservoirs. Through simulation of biological translation, the algorithm
      allows the prediction of the effect of contamination levels on the number of
      mutations to occur for any given peptide sequence. In this study the cholinergic
      binding site was used as a model sequence (22 amino acids). Considerations, based
      on the computer program, are discussed regarding the efficient design of phage
      display combinatorial libraries.

PMID- 7630885
TI  - Alteration of the amino acid substrate specificity of clostridial glutamate
      dehydrogenase by site-directed mutagenesis of an active-site lysine residue.
AB  - Two residues, K89 and S380, thought to interact with the gamma-carboxyl group of
      the substrate L-glutamate, have been altered by site-directed mutagenesis of
      clostridial glutamate dehydrogenase (GDH). The single mutants K89L and S380V and
      the combined double mutant K89L/S380V were constructed. All three mutants were
      satisfactorily overproduced in soluble form. However, only the K89L mutant was
      retained by the dye column normally used in purifying the wild-type enzyme. All
      three mutant enzymes were purified to homogeneity and tested for substrate
      specificity with 24 amino acids. The single mutant S380V showed no detectable
      activity. The alternative single mutant K89L showed an activity towards L
      glutamate that was decreased nearly 2000-fold compared with wild-type enzyme,
      whereas the activities towards the monocarboxylic substrates alpha-aminobutyrate
      and norvaline were increased 2- to 3-fold. A similar level of activity was
      obtained with methionine (0.005 U/mg) and norleucine (0.012 U/mg), neither of
      which give any activity with the wild-type enzyme under the same conditions. The
      double mutant showed decreased activity with all substrates compared with the
      wild-type GDH. In view of its novel activities, the K89L mutant was investigated
      in greater detail. A strictly linear relationship between reaction velocity and
      substrate concentration was observed up to 80 mM L-methionine and 200 mM L
      norleucine, implying very high Km values. Values of kcat/Km for L-methionine and
      L-norleucine were 6.7 x 10(-2) and 0.15 s-1 M-1, respectively.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7630886
TI  - Identification of interaction site of pseudoazurin with its redox partner, copper
      containing nitrite reductase from Alcaligenes faecalis S-6.
AB  - Pseudoazurin, a low molecular weight protein containing a single type I copper,
      functions as an electron donor to a copper-containing nitrite reductase (NIR) in
      a denitrifying bacterium Alcaligenes faecalis S-6. To elucidate the protein
      protein interaction between these two copper-containing proteins, each of nine
      out of 13 lysine residues on the surface of pseudoazurin were independently
      replaced by alanine or aspartate, and the effects of the mutations on the
      interaction with NIR, as well as the physicochemical properties of pseudoazurin,
      were analyzed. All of the mutated pseudoazurins showed optical spectra and
      oxidation-reduction potentials almost identical to those of wild-type
      pseudoazurin, suggesting that none of the replacements of these lysine residues
      affected the environment around the type I copper site. Kinetic analysis of
      electron transfer between mutated pseudoazurins and NIR reveals that the lysine
      mutations have very little effect on the rate of electron transfer to NIR, but
      substitution at residues 10, 38, 57 and 77, all close to the copper site,
      substantially decreases the affinity of pseudoazurin for NIR. This suggests that
      pseudoazurin interacts with NIR through the region close to the type I copper
      site. The refined X-ray structures of Lys38Asp and Lys10Asp/Lys38Asp show that
      the molecular structure has indeed changed little. A new space group is observed
      for the Lys109Ala mutant crystal. Crystal packing interactions change for the
      Lys10Asp/Lys38Asp mutant but remain the same for Lys38Asp and Lys59Ala mutants.

PMID- 7630887
TI  - Insertional re-activation of a chloramphenicol acetyltransferase misfolding
      mutant protein.
AB  - The deletion of nine residues from the C-terminus of the bacterial
      chloramphenicol acetyltransferase (CAT) results in deposition of the mutant
      protein in cytoplasmic inclusion bodies and loss of chloramphenicol resistance in
      Escherichia coli. This folding defect is relieved by C-terminal fusion of the
      polypeptide with as few as two residues. Based on these observations, efficient
      positive selection for the cloning of DNA fragments has been demonstrated. The
      cloning vector encodes a C-terminally truncated CAT protein. Restriction sites in
      front of the stop codon allow the insertion of target DNA, resulting in the
      production of properly folded CAT fusion proteins and regained chloramphenicol
      resistance. The positive selection of recombinants is accomplished by growth of
      transformants on chloramphenicol-containing agar plates. The method appears
      particularly convenient for the cloning of DNA fragments amplified by the PCR
      because minimal information to restore CAT folding can be included in the
      primers. The cloning of random sequences shows that the folding defect can be
      relieved by fusion to a wide variety of peptides, providing great flexibility to
      the positive selection system. This vector may also contribute to the
      determination of the role of the C-terminus in CAT folding.

PMID- 7630888
TI  - Production, characterization and cytotoxic properties of a diphtheria toxin
      ciliary neurotrophic factor fusion protein.
AB  - Ciliary neurotrophic factor (CNTF) is a multifunctional cytokine that can
      regulate the survival and differentiation of many types of developing and adult
      neurons. This study describes the genetic construction, expression, purification
      and properties of a diphtheria toxin-related CNTF fusion gene in which the native
      receptor binding domain of diphtheria toxin was genetically replaced with a
      synthetic gene encoding human CNTF. The fusion protein expressed from the
      chimeric tox gene was designated DAB389-CNTF. This fusion toxin has a deduced
      molecular weight of 67 440 and is formed by the fusion of the first 389 amino
      acids of diphtheria toxin to amino acids 15-200 of mature human CNTF (Cys17-
      >Ser), using a bridge of 34 additional amino acids including six consecutive
      histidine residues. This latter span allows for a single-step purification of the
      fusion protein by Ni(2+)-immobilized metal ion affinity chromatography, and
      provides a degree of flexibility which facilitates polypeptide refolding. DAB389
      CNTF was selectively cytotoxic for clonal cells bearing CNTF receptors and for
      CNTF-responsive spinal sensory ganglion neurons in primary culture. The cytotoxic
      action of DAB389-CNTF, like that of native diphtheria toxin, required receptor
      mediated endocytosis, passage through an acidic compartment and delivery of an
      ADP-ribosyltransferase to the cytosol of target cells. The delivery of the
      catalytic domain to the target cell cytosol results in inhibition of protein
      synthesis and cell death. This latter point was confirmed by the observation that
      both CNTF and DAB389-CNTF increased c-fos mRNA expression, but only CNTF induced
      Fos protein.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7630889
TI  - Effective renaturation of reduced lysozyme by gentle removal of urea.
AB  - To increase the folding yield of concentrated reduced lysozyme, we developed a
      renaturation method by means of dialysis from concentrated urea with redox
      agents. After lysozyme was incubated in the reducing buffer (8 M urea solution)
      with oxidized glutathione, renaturation of reduced lysozyme was started by
      dialysis against the dialyzing buffer containing 8 M urea with redox agents. The
      urea concentration of the dialyzing bottle was gradually diluted with dialyzing
      buffer without urea at a flow rate of 0.1 ml/min by high pressure pump. Using
      this systematic dialysis, a concentration as high as 5 mg/ml of reduced lysozyme
      could be renaturated in 80% yield, while the folding yield was < 5% even at a
      concentration of 1 mg/ml using a conventional rapid dilution method [Goldberg et
      al. (1991) Biochemistry, 30, 2790-2797]. Therefore, it was concluded that gentle
      removal of urea from denatured proteins, dissolved in concentrated urea solution,
      by means of dialysis should be useful to renature denatured proteins effectively.

PMID- 7630890
TI  - Predicted beta-structure stability parameters under experimental test.
AB  - Recently, beta-structure stability parameters have been measured for all 20
      natural amino acids, separately for the edge and separately for the internal beta
      sheet positions. Theoretical estimations of all these stability parameters have
      been obtained earlier on the basis of the molecular theory. Comparison shows a
      good concordance between the recent experimental results and the earlier
      theoretical predictions.

PMID- 7630891
TI  - A strategy for the de novo design of helical proteins with stable folds.
AB  - This paper describes peptide analogs and the design strategy that were used to
      facilitate the final construction of a de novo-designed protein (ALIN) whose
      stable tertiary fold has been determined recently by NMR spectroscopy. Previous
      studies have suggested that the main problem in the de novo design of proteins is
      the attainment of a protein with a defined fold. To effectively overcome this
      mainchain multiconformation problem, three related steps, with experimental
      evaluation of the design hypotheses for each step, were pursued in the design
      process. Firstly, 15-residue sequences with experimentally verified high
      helicites were selected for the helical regions. Secondly, hydrophobic and
      electrostatic interhelical interactions as well as an interhelical disulfide
      bridge were designed to favor an antiparallel configuration of the helix axis.
      Finally, a loop with sufficient flexibility was inserted to stabilize the helices
      in the desired orientation. To assess the design strategy, peptides corresponding
      to each design step were synthesized and their structures verified experimentally
      by far-UV CD. As anticipated, ALIN was the most helical, and the SS-bridged
      dimeric peptides were more helical than their monomeric counterparts. The van't
      Hoff enthalpy change for ALIN computed from the CD denaturation curve and
      assuming a two-state model was 50 kJ/mol, a value close to that observed for
      helical coiled-coils. Overall, this report shows that small, simple proteins can
      be built using the current knowledge of protein structures.

PMID- 7630892
TI  - HIV transmission in sexual networks: an empirical analysis.
AB  - Risk behaviour and egocentric sexual network data collected from a large random
      sample of young gay men in San Francisco were analysed to assess the importance
      of sexual mixing (i.e. sexual networks) in the acquisition of HIV. These data
      were collected in 1993, during wave one of a longitudinal cohort study of HIV
      transmission in gay men; the seroprevalence level in the sample was 18%. We
      identify recent sexual mixing patterns and we demonstrate that seropositives and
      seronegatives have very different age-stratified sexual mixing patterns. We show
      that sexual mixing can explain the current seroprevalence patterns in the young
      gay community; seroprevalence levels in risk groups reflect the degree of sexual
      mixing with the older (and more heavily infected) age group. Our results suggest
      that seropositives became infected with HIV not simply owing to an increased rate
      of acquisition of sex partners, but also as a result of their sexual mixing
      pattern. We develop and apply a simple methodology that uses the sexual network
      data in combination with risk behaviour data to estimate the future number of
      seroconverters. Our methodology is validated by testing our predictions against
      the observed seroconversion data collected during wave two of the cohort study in
      1994. Our analyses empirically demonstrate (for the first time) the significance
      of sexual mixing as a risk factor for HIV transmission.

PMID- 7630893
TI  - MHC-dependent mate preferences in humans.
AB  - One substantial benefit of sexual reproduction could be that it allows animals
      (including humans) to react rapidly to a continuously changing environmental
      selection pressure such as coevolving parasites. This counteraction would be most
      efficient if the females were able to provide their progeny with certain allele
      combinations for loci which may be crucial in the parasite-host arms race, for
      example the MHC (major histocompatibility complex). Here we show that the MHC
      influences both body odours and body odour preferences in humans, and that the
      women's preferences depend on their hormonal status. Female and male students
      were typed for their HLA-A, -B and -DR. Each male student wore a T-shirt for two
      consecutive nights. The next day, each female student was asked to rate the
      odours of six T-shirts. They scored male body odours as more pleasant when they
      differed from the men in their MHC than when they were more similar. This
      difference in odour assessment was reversed when the women rating the odours were
      taking oral contraceptives. Furthermore, the odours of MHC-dissimilar men remind
      the test women more often of their own actual or former mates than do the odours
      of MHC-similar men. This suggests that the MHC or linked genes influence human
      mate choice today.

PMID- 7630894
TI  - Differential male genetic success determines gene flow in an experimentally
      manipulated mouse population.
AB  - Sexual selection arises when genetically different males show heritable
      differences in reproductive success. Mouse mating behaviour involves both male
      competition and female choice. In this paper we show that introduced Y-linked DNA
      markers spread more extensively through a natural population than do genes
      inherited matrilineally. Differences in mating success between the sexes and
      among individual males may alter the pattern and rate of gene flow in natural
      populations. Another interesting possibility is that the success of the
      introduced Y chromosome may be attributable to so-called 'selfish' traits, such
      as sex-linked meiotic drive or intra-uterine competition. However, this study
      provides little unequivocal evidence to support this view. Differential success
      of introduced versus resident males may have implications for the reintroduction
      of endangered mammals into residual wild populations.

PMID- 7630896
TI  - A classification of replicators and lambda-calculus models of biological
      organization.
AB  - W. Fontana & L.W. Buss (Proc. Natn. Acad. Sci. U.S.A. 91, 757 (1994) and Bull.
      math. Biol. 56, 1 (1994) have put forward a scheme for a theory of biological
      organization based on the lambda-calculus. Their key innovation was to represent,
      with the aid of this calculus, a certain minimal chemistry. Although this idea is
      very promising, their concrete formulation could be improved if suggestions for
      the following items were incorporated: (i) a better coding of chemical reactions;
      (ii) a reinterpretation of the evolutionary behaviour of autocatalytic chemical
      networks; (iii) a better appreciation of morphological and genetic factors; (iv)
      a more complete embedding of the theory into the background of relevant earlier
      contributions. Confusion can be stopped by the application of a proper
      classification of replicators (important categories being: processive and
      modular, limited and unlimited hereditary replicators). Suggestions to facilitate
      improvement are made explicit in this paper. The most challenging task would be
      to model the transition from processive, limited hereditary replicators to
      modular replicators with limited and unlimited heredity.

PMID- 7630895
TI  - A contrast ratio constraint on stereo matching.
AB  - Stereopsis employs differences in the location of features in the two eyes to
      reconstruct their relative depths. Computational models largely ignore the
      contrast of these features; they simply require them to be visible in each eye
      and to possess the same contrast polarity. With a competitive matching paradigm
      we show that only features with a certain ratio of contrasts in the two eyes
      match. Increasing the contrast in one eye requires proportionally more contrast
      in the other eye for matching. This contrast relation exactly parallels the
      relation found for dichoptic masking, which behaves unlike any other form of
      contrast masking. A strange consequence of this contrast ratio constraint is that
      a feature may be monocularly visible, yet unmatched because the contrast ratio
      has not been satisfied. In this case features are seen as faint unmatched
      'ghosts' near the plane of fixation. In a competitive matching situation then,
      stereopsis acts as if it imposes a contrast threshold on matches; features
      failing to exceed the threshold remain unmatched. This is a simple and
      biologically plausible way for the system to eliminate false matches and to
      reduce matching ambiguity.

PMID- 7630897
TI  - Explaining local species diversity.
AB  - In this paper we examine the explanations for local species diversity. Using six
      extensive data-sets for drosophilid flies (which include both temperate and
      tropical species) we compare three major categories of explanation (Cornell &
      Lawton 1992): niche heterogeneity (resource partitioning), spatial heterogeneity
      (intraspecific aggregation), and the fullness of the niche space (saturation
      level). We conclude that these Drosophila communities are dominated by
      intraspecific aggregation, not by resource partitioning, and they are not fully
      saturated.

PMID- 7630898
TI  - The population dynamics of vertically and horizontally transmitted parasites.
AB  - We analyse a model of the transmission dynamics of a parasite transmitted both
      vertically and horizontally. The basic reproductive ratio (R0) of the parasite is
      shown to be a sum of horizontal and vertical components. We derive expressions
      for the equilibrium prevalence of infection for a mixture of horizontal and
      vertical transmission; prevalence can reach 100% if transmission is sufficiently
      high. At the endemic equilibrium, if prevalence is high, most transmission will
      in general be vertical, but horizontal transmission rates must be high to reach
      and stably maintain such an equilibrium. Surprisingly, for such parasites the
      highest equilibrium rates of vertical transmission are observed when horizontal
      transmission is very effective. We discuss the implications for assessing the
      importance of horizontal v. vertical transmission from field data, and we suggest
      some implications for the evolution of virulence.

PMID- 7630899
TI  - Macroevolutionary inferences from primate phylogeny.
AB  - We apply new statistical methods to a recent estimate of the phylogeny of all
      living primate species to test a range of models of cladogenesis. Null models in
      which probabilities of speciation and extinction do not differ among
      contemporaneous lineages are not consistent with the phylogeny. We present
      evidence that the net rate of cladogenesis (speciation rate minus extinction
      rate) increased in the lineage leading to the Cercopithecidae (Old World
      monkeys), and that there have been further increases in some lineages within that
      family. Such increases suggest the occurrence of clade selection, although we
      have not identified the selected trait or traits. There is no evidence that the
      net rate of cladogenesis is a function either of how many primate lineages are
      already present or of time. Intriguingly, three other clades--Strepsirhini,
      Platyrrhini and Hominoidea--appear to have had very similar rates of clade
      growth, in spite of their great biological differences.

PMID- 7630900
TI  - Motion-from-hue activates area V5 of human visual cortex.
AB  - We designed experiments to ascertain whether area V5 of human visual cortex is
      activated by a motion stimulus in which luminance is made irrelevant, and motion
      is generated from hue differences alone. The stimuli consisted of moving green
      squares or bars against a red background, masked with luminance noise. Changes in
      regional cerebral blood flow (rCBF) were determined by the technique of positron
      emission tomography and the brain images thus derived were co-registered with
      magnetic resonance images of the same brain to identify the anatomical locations
      of the blood flow changes. The results showed that when subjects perceived
      motion, a change in rCBF occurs in areas V5, V1/2, V3 and the parieto-occipital
      sulcus but not V4, even though the moving stimulus was defined by hue. We
      conclude that the motion-specialized areas of the visual cortex can use
      information derived from any source to undertake their function.

PMID- 7630901
TI  - Sex allocation and population structure in malaria and related parasitic
      protozoa.
AB  - Here we demonstrate how sex allocation theory, one of the best verified areas of
      metazoan evolutionary biology, can be successfully applied to microparasitic
      organisms, by relating parasite prevalence and sex ratio in the Haemosporina.
      Members of this taxon, which includes Plasmodium, are parasitic protozoa with
      obligate sexual cycles in which dioecious haploid gametes drawn from the
      peripheral blood of a vertebrate host fuse within a dipteran vector. Consequently
      mating takes place within a highly subdivided population, a condition known to
      promote local mate competition and inbreeding and hence the evolution of female
      biased sex ratios. We used an epidemiological framework to investigate mating
      patterns and sex ratio evolution within natural populations of these parasites.
      This phenotypic approach compliments more conventional biochemical approaches to
      the population genetics of parasitic protozoa. Data are presented which support a
      theoretical relation between transmission-stage sex ratio and prevalence across
      parasite populations. These results are consistent with a large inter-population
      variation in genetic structure and argue against sweeping generalizations about
      the clonality or otherwise of populations of these parasitic protozoa.

PMID- 7630902
TI  - Accountability in practice. Part 4: Accountability and change in clinical
      practice.

PMID- 7630903
TI  - Research ethics.

PMID- 7630904
TI  - Sleep apnoea.

PMID- 7630905
TI  - The reorganisation of a dermatology department.
AB  - In one dermatology unit, work patterns were restructured to improve continuity of
      care. The creation of nursing teams working in both the ward and outpatients'
      department has meant the effective use of nursing resources and multi-skilling of
      nursing staff.

PMID- 7630906
TI  - Enteral feeding pumps.
AB  - Enteral tube feeding is a relatively safe way of meeting nutritional
      requirements. Pumps are a reliable and cost-effective means of feeding. Nurses
      should consider the range of options available when choosing a pump. The cost of
      disposables should always be taken into account.

PMID- 7630907
TI  - Spiritual pain in dying people: the nurse's role.
AB  - Spirituality is a vital aspect of health care, as it affects physical,
      psychological and social needs. In a dying person spiritual pain may preclude a
      peaceful death. Nurses are in an ideal position to assess, plan and provide care
      for those in spiritual pain. 'Being with' a person in spiritual pain is often
      more important than any intervention. Evaluation of relief from spiritual pain is
      often difficult but should be attempted.

PMID- 7630908
TI  - Psychological implications of advances in genetics--3 predictive testing.
AB  - The psychosocial effects of genetic testing on individuals and families are
      complex, and the implications should be considered carefully. Testing of children
      for carrier status or adult-onset conditions is not usually advised.
      Professionals need to be aware of the complexity of the issues affecting clients
      and provide appropriate education and support.

PMID- 7630909
TI  - Preventing pressure sores in patients' homes.
AB  - The size of the pressure sore problem in community patients is virtually unknown
      and further research is necessary in this area. Pressure sore prevention can be
      more difficult in community patients because of problems specific to that sector
      such as lack of observation, reliance on carers, poor nutrition and lack of
      resources. District nurses need supportive services, multidisciplinary backing,
      education and equipment if they are to take the lead in this area.

PMID- 7630910
TI  - Treatment of nocturnal enuresis in nursing homes.
AB  - A number of age-related physiological changes can result in nocturnal enuresis.
      Prescribed medication can also affect continence. Assessment should rule out
      pathological causes. A number of nursing interventions can help restore
      continence in older people.

PMID- 7630911
TI  - Reusing dialysers in the care of renal patients.
AB  - Reprocessing dialysers was originally undertaken as a cost-saving measure.
      Reprocessing reduces incidence of 'first use syndrome'. Significant cost savings
      may be made with reprocessing. If procedures are carried out correctly, and
      patients are carefully monitored, reprocessing carries no added risk to patients.

PMID- 7630913
TI  - Twice monthly bibliography on prostaglandins biology--early February prepared by
      SUBIS.

PMID- 7630912
TI  - Mouth care for patients receiving oral irradiation.
AB  - Oral irradiation causes acute mucositis and pain, dry mouth, loss of taste,
      impaired nutrition, depression and isolation. These problems can be significantly
      improved by skilled, research-based nursing care. The most important factors in
      oral care are frequent mechanical cleansing, good pain control, effective
      management of candida and regular, structured evaluation. An oral care regime
      using saline rinses may be more effective than a regime using a more astringent
      mouthwash. The use of an oral assessment guide and protocol ensures that all
      patients receive the same high-quality care. They simplify documentation and are
      useful audit tools and teaching aids.

PMID- 7630914
TI  - Eicosanoids and asthma: an update.
AB  - There have been significant advances in our understanding of the role of
      eicosanoids as mediators in inflammation since their discovery over 50 years ago.
      Our more recent understanding of asthma as an inflammatory disease has led to the
      appreciation of eicosanoids potentially being pivotal mediators in promoting some
      of the changes in asthma. Of particular importance are the cysteinyl LTs in
      producing bronchospasm and bronchial hyperresponsivenss, and PGE2 in modulating
      the bronchospastic and inflammatory response. Evidence from clinical studies
      suggests that other eicosanoids may also contribute, but their importance is
      secondary and their relative contributions vary between individuals. The
      development of new drugs based on our partial understanding of the role that
      eicosanoid mediators may play in asthma promises new approaches to the treatment
      of this common chronic inflammatory condition.

PMID- 7630915
TI  - Changes in the fatty acid composition of immune cells and plasma by intravenous
      injection of dihomo-gamma-linolenic acid in mice.
AB  - An injectable emulsion of 10% tridihomo-gamma-linolenoyl glycerol (DGLA-TG, 96%
      pure) was prepared. 0.5 ml of the emulsion was injected into tail veins of 6-week
      old C3H/HeSlc mice. They were killed 1, 3, 6, 12 and 24 h after the injection.
      The fatty acid composition of the phospholipid (PL) fraction of plasma,
      splenocytes and thymocytes was analysed along with that of control mice. DGLA
      concentrations increased markedly 1 h after the injection in the plasma (from
      2.2% to 13.2%) and splenocyte (from 1.1% to 10.1%) PL fractions; they decreased
      rapidly thereafter. On the other hand, DGLA concentrations in the thymocyte PL
      fraction did not increase markedly. These data may be useful for planning animal
      experiments with DGLA emulsions, should these be developed as an experimental
      drug in the future.

PMID- 7630916
TI  - Essential fatty acids are antagonists of the leukotriene B4 receptor.
AB  - A series of essential fatty acids and fatty acid derivatives were evaluated for
      their ability to inhibit [3H] leukotriene B4 (LTB4) binding to pig neutrophil
      membranes. The fatty acids varied in chain length, extent of unsaturation,
      position of unsaturation, and isomerization. Generally, fatty acids with two or
      more unsaturated sites and chain lengths of 18-22 were potent inhibitors of
      [3H]LTB4 binding; both n-3 and n-6 fatty acids were inhibitory. The most potent
      compounds tested were homogammalinolenic acid and ricinelaidic acid which gave Ki
      values of 1 microM and 2 microM in the binding assay. Ricinelaidic acid was also
      tested for its ability to inhibit LTB4-mediated chemotaxis (IC50 = 10 microM) and
      LTB4-induced calcium fluxes (IC50 = 7 microM) in isolated human neutrophils.
      Ricinelaidic acid did not show agonist activity in these assays. In an in vivo
      model of LTB4-induced bronchoconstriction, ricinelaidic acid and
      homogammalinolenic acid gave 46% and 53% inhibition, respectively, at a 1 mg/kg
      i.v. dose. These results indicate that essential fatty acids are LTB4 receptor
      antagonists, which may account in part for their reported anti-inflammatory
      activities.

PMID- 7630917
TI  - Phenols inhibit prostaglandin E2 synthesis in A23187-stimulated human whole blood
      and modify the ratio of arachidonic acid metabolites.
AB  - We have previously demonstrated that the phenolic compounds catechol,
      hydroquinone, and phenol increase the prostaglandin (PG) E2/leukotriene (LT) B4
      ratio in human polymorphonuclear leukocytes (PMNs), while resorcinol has the
      opposite effect. However, in human whole blood phenols have a different effect on
      the thromboxane (TX) B2/LT ratio than in PMNs on the PGE2/LTB4 ratio. To
      establish whether the discrepancy between the results of our previous studies is
      due to different indicators of prostaglandin H synthase activity in PMNs (PGE2)
      and in whole blood (TXB2), we measured the effect of phenols on PGE2 synthesis in
      whole blood. The phenols only inhibited PGE2 synthesis (IC50 values for
      resorcinol, catechol, hydroquinone, and phenol of 10 microM, 10 microM, 60 microM
      and 700 microM, respectively). No significant stimulatory activity was seen as
      earlier in PMNs. Thus, the effect of phenols on PGE2 synthesis in whole blood is
      different from that in PMNs, although their order of potency to inhibit PGE2
      synthesis is the same.

PMID- 7630918
TI  - Effect of cytotoxic prostaglandin, delta 12-prostaglandin J2 on E-cadherin
      expression in transformed epidermal cells in culture.
AB  - The cyclopentenone prostaglandins (PGs), such as delta 12-PGJ2 and PGA1, are
      potent inhibitors of growth in a variety of cultured cells, including human
      epidermal cells. To clarify the mechanism of the cytotoxicity of these PGs, we
      examined the effects of delta 12-PGJ2 on the function and expression of E
      cadherin, which plays a major role in the maintenance of intercellular adhesion,
      in transformed human epidermal cells in culture (HSC-1). A 12-h incubation with 5
      micrograms/ml of delta 12-PGJ2 did not affect the cell-binding activity of E
      cadherin expressed in HSC-1 cells. Immunoblot analysis using a monoclonal
      antibody specific to human E-cadherin revealed that a 12-h incubation with 5
      micrograms/ml of delta 12-PGJ2 induced E-cadherin expression in HSC-1 cells.
      Immunofluorescence using a monoclonal antibody against human E-cadherin
      demonstrated that E-cadherin was localized to the cell-cell contact regions in
      HSC-1 cells. Following a 12-h incubation with 5 micrograms/ml of delta 12-PGJ2, E
      cadherin was also detected in a uniform pattern along cell junctions, although
      cell morphology was changed by the presence of cytotoxic PGs. These results
      suggest that the cytotoxicity of cyclopentenone PGs is related, at least in part,
      to E-cadherin expression in transformed human epidermal cells.

PMID- 7630919
TI  - Inhibition of PAF-induced human platelet aggregation by antithrombotic
      nipecotomides.
AB  - Nipecotamides (piperidine-3-carboxamides) are potent inhibitors of platelet
      aggregation induced by a variety of agonists in vitro and in vivo. The inhibitory
      effects of six structural types of nipecotamides on human platelet aggregation
      induced by platelet-activating factor (PAF) in vitro, are studied. Evaluation of
      15 racemates and stereoisomers of two nipecotamides showed that bis-nipecotoyl
      alkanes were more active than their mono congeners. Mono- and bis-nipecotoyl
      decanes were more potent than the corresponding hexanes. Lipophilicity was found
      to play a significant role in the antiplatelet activity of these compounds. The
      stereoselectivity in the PAF-antagonist potential of nipecotamides was less
      pronounced than that resulting from their action on ADP- or collagen-induced
      aggregation. Oxidation of the two benzylic carbon atoms of alpha, alpha'-bis[3
      (N,N-diethylcarbamoyl)piperidino]-p-xylene.2HBr (A-1) to form 1,4-bis[3-N,N
      diethylcarbamoyl) piperidino]benzenedicarboxamide (A-40K), which has a second set
      of carbonyl oxygens but lacks basic N atoms, resulted in a remarkable loss of ADP
      antagonist potency while retaining PAF-antagonist activity. It is suggested that
      in addition to their membrane effects, nipecotamides act at other sites,
      including the PAF receptor. Double reciprocal plots of PAF binding to gel
      filtered platelets (GFP) in the presence and absence of a typical nipecotamide (A
      1C) were indicative of competitive inhibition (Ki = 19.28 microM). Scatchard
      analysis of 3H-PAF binding to GFP suggested the presence of high, intermediate
      (I) and low affinity binding sites, of which the I site gave a KD/app of 0.332 nM
      with an estimated 564 sites/platelet. Key interactions of nipecotamides with the
      PAF receptor appear to be the following (i) electrostatic interactions of the two
      amide oxygens with a primary set of electropositive areas spaced at 5-7 A, (ii)
      in the case of appropriate compounds, electrostatic interactions of the two amide
      oxygens spaced at 10-12 A with corresponding secondary receptor sites carrying
      positive electrostatic potential, (iii) a hydrophobic moiety fitting into a
      hydrophobic pocket in the receptor, and (iv) the cationic piperidine N+ (at pH
      7.4) interacting with a counterion, probably aspartic acid.

PMID- 7630920
TI  - Function of Ca2+ influx in phospholipase D activation induced by prostaglandin F2
      alpha in osteoblast-like cells: involvement of tyrosine kinase.
AB  - We previously reported that prostaglandin F2 alpha (PGF2 alpha) induces Ca2+
      influx from the extracellular space via protein tyrosine kinase in osteoblast
      like MC3T3-E1 cells and that PGF2 alpha stimulates phosphatidylcholine
      hydrolyzing phospholipase D in these cells (6, 12). In this study, we examined
      the relationship between the tyrosine kinase-regulated Ca2+ influx by PGF2 alpha
      and the activation of phospholipase D in MC3T3-E1 cells. The depletion of
      extracellular Ca2+ by [ethylenebis(oxyethylenenitrilo)]tetraacetic acid (EGTA)
      markedly reduced the PGF2 alpha-induced formation of choline. Genistein, an
      inhibitor of protein tyrosine kinases, which by itself had little effect on
      choline formation, significantly suppressed the formation of choline induced by
      PGF2 alpha in a dose-dependent manner. Tyrphostin, an inhibitor of protein
      tyrosine kinases chemically distinct from genistein, also suppressed the PGF2
      alpha-induced formation of choline. Sodium orthovanadate, an inhibitor of protein
      tyrosine phosphatases, significantly enhanced the PGF2 alpha-induced formation of
      choline. These results strongly suggest that the phospholipase D activation by
      PGF2 alpha is dependent on extracellular Ca2+ in osteoblast-like cells and that
      protein tyrosine kinase is involved in the activation of phospholipase D.

PMID- 7630921
TI  - Effect of glibenclamide on the metabolism of fatty acids in cultures of newborn
      rat heart cells under normoxic and hypoxic conditions.
AB  - Several deleterious biochemical alterations have been observed in myocardial
      cells during ischemia, including perturbations of transmembrane ion equilibria,
      production of noxious oxygen-derived radicals and loss of membrane phospholipids.
      Although the precise relationship between these alterations and the reduction of
      oxygen and glucose supplies is not fully understood, the decrease of
      intracellular ATP content appears to be a key event in the cascade. Recent
      evidence suggests that opening of ATP-sensitive K+ channels may constitute an
      endogenous protective mechanism during ischemia. We have thus tested the effects
      of glibenclamide, a channel blocker, and aprikalim, a channel opener, on the
      metabolism of membrane fatty acids in cultures of newborn rat heart cells under
      normoxic and hypoxic conditions. We showed that glibenclamide partially blocks
      the loss of membrane phospholipids induced by oxygen deprivation in contractile
      myocytes, whereas aprikalim fails to alter this metabolism under either normoxic
      or ischemic conditions. In cultures of fibroblast-like heart cells neither drug
      was able to modify fatty acid metabolism.

PMID- 7630922
TI  - Prostaglandin E2 alters terminal glycosylation of high molecular weight
      glycoproteins, released by pig gastric mucous cells in vitro.
AB  - The gastric mucus layer consists of high molecular weight glycoproteins (HMG). E
      Type prostaglandins (PGs) stimulate total HMG release from isolated gastric
      mucous cells. We determined the effects of PGE2 on HMG glycosylation. Pig gastric
      mucous cells were cultured for 20 h with 1 mumol/l PGE2. Released HMG were
      isolated by gel chromatography and periodic acid-Schiff (PAS)-positive sugars and
      protein-bound [14C]GlcNAc were determined. Monosaccharides terminally linked to
      HMG oligosaccharide chains were monitored by lectin enzyme linked immunosorbent
      assay (ELISA): N-acetylglucosamine (GlcNAc) with Datura stramonium agglutinin, N
      acetylgalactosamine (GalNAc) with soy bean agglutinin, fucose (Fuc) with Ulex
      europaeus I agglutinin and sialic acids (Sial) with Sambucus nigra agglutinin.
      PGE2 stimulated total HMG release, indicated by an increase of PAS-positive
      sugars to 170% and [14C]GlcNAc to 220% of controls. Terminal GlcNAc increased to
      128%, GalNAc to 133%, Fuc to 165% and Sial to 182%. In addition to stimulation of
      total HMG release, PGE2 caused alterations of HMG glycosylation, which may
      modulate HMG viscosity and microbiological barrier function.

PMID- 7630923
TI  - Differential effects of endothelial cell fatty acid modification on the
      sensitivity of their membrane phospholipids to peroxidation.
AB  - In order to study the relationship between the fatty acid (FA) composition of
      human umbilical vein endothelial cells (HUVEC) and their susceptibility to
      oxidative stress, we modified their FA composition by long-term culturing in
      media supplemented with a saturated, monounsaturated, or polyunsaturated FA.
      Sensitivity of the cellular phospholipids to peroxidation was monitored by
      measuring conjugated diene formation and decrease of polyunsaturated FAs induced
      by CuSO4 and H2O2 in liposomes prepared from the respective phospholipid
      extracts. The extent of phospholipid peroxidation was found to increase with
      increasing content of polyunsaturated FAs. In addition, the sensitivity of
      individual polyunsaturated FAs to peroxidation was directly proportional to the
      number of double bonds present. However, no unequivocal relationship was observed
      between conjugated diene formation and the phospholipid unsaturation index (an
      indicator for the combined effect of number of double bonds and polyunsaturated
      FA contents of the membrane phospholipids). The results suggest that long-term FA
      modification of endothelial cells differentially alters the sensitivity of their
      membrane phospholipids to peroxidation: long-term modification with oleic acid
      may protect against lipid peroxidation, whereas linoleic acid may increase
      sensitivity to peroxidation. In contrast to what might be expected, long-term
      modification of endothelial cells with eicosapentaenoic or docosahexaenoic acid
      does not increase the sensitivity of phospholipids to peroxidation.

PMID- 7630924
TI  - The effect of essential fatty acid supplementation on keratinocyte replication.
AB  - Epidermal cell growth in culture, using the low calcium, low serum technique
      described by Boyce, is thought to induce rapid expansion by inducing an essential
      fatty acid (EFA) deficiency state. To determine the mechanisms whereby EFA
      deficiency induces increased epidermal cell growth, keratinocytes were passaged
      into medium without or with the addition of EFAs, 18:2(n-6), 20:4(n-6). The
      resulting populations were assayed for replication rate, differentiation, and
      plating efficiency. Supplemental EFAs significantly decrease keratinocyte culture
      expansion. This is evidenced by an increase in generation time, a decrease in
      thymidine incorporation, and a decrease in modeled replication rate. EFA
      supplementation also increased the expression of cornified cell envelopes. Serum
      free medium induces EFA deficient keratinocytes that demonstrate increased
      replication and decreased differentiation. Restoration of EFAs reverses these
      changes. It may be possible to manipulate keratinocyte physiology using fatty
      acid modifications.

PMID- 7630925
TI  - Ursodeoxycholic acid therapy of chronic cholestatic conditions in adults and
      children.
AB  - Cholestasis can be defined as the manifestation of defective bile acid transport
      from the liver to the intestine. Most chronic cholestatic conditions can progress
      towards cirrhosis. At this stage, liver transplantation is the treatment of
      choice. Most of the drugs so far evaluated show some degree of efficacy but have
      major side effects. Given that ursodeoxycholic acid (UDCA) has no apparent
      toxicity in humans, it was postulated that long-term treatment with this drug
      might displace endogenous bile acids and thus reverse their suspected toxicity.
      We demonstrated that long-term UDCA therapy slows the progression of primary
      biliary cirrhosis and reduces the need for liver transplantation. In this review,
      we give the rationale for the use of UDCA in cholestasis and discuss its possible
      mechanisms of action. We also give an overview of current data on UDCA therapy of
      chronic cholestatic disorders in adults and children.

PMID- 7630926
TI  - 5-Hydroxytryptamine pathways in anxiety and its treatment.
AB  - The effects of manipulating 5-hydroxytryptamine (5HT) neuronal function in humans
      and in animals are reviewed. 5HT pathways do not have a unitary function in
      modulating anxiety. It is proposed that, rather than acting as input or output
      channels for brain aversive systems, these pathways provide information
      concerning waking/motor status, which is crucial to the organisation of
      appropriate responses to threat. Each terminal region can make use of this
      information in different ways. Globally, the influence of 5HT neurones on higher
      centres appears predominantly to facilitate information processing relevant to
      threat, while their major influence on brainstem centres may be a restraining
      one.

PMID- 7630927
TI  - Morphology of cerebral arteries.
AB  - A comparison of the major cerebral arteries between humans and rats shows many
      similarities, including anomalies in their general organization, the structure of
      these vessels at the light and electron microscope levels and their morphological
      changes associated with cerebral vascular diseases. The general organization of
      the major cerebral arteries shows the following main differences between humans
      and rats. In rats, the internal carotid arteries have become an integral part of
      the circle of Willis. In the anterior cerebral arteries, a common variation in
      humans is the underdevelopment of one of the two arteries, whereas in rats,
      buttonhole-like structures are common in one or both arteries. The anterior
      communicating artery present in humans is absent in rats. The olfactory artery is
      prominent in rats, but absent in humans. The posterior communicating artery in
      humans is the most variable component of the circle of Willis, being asymmetric
      in its origin, diameters and branches. Similarly, the posterior cerebral arteries
      in rats often exhibit asymmetrical origin from the basilar artery. There was some
      confusion in the literature regarding the name of the posterior cerebral arteries
      in rats, but this was caused mainly by misquotations and incorrect
      interpretations of the papers. In humans, most aneurysms occur in the anterior
      half of the circle of Willis, and the incidence is higher in females than males;
      the middle cerebral artery is most often the one to become occluded, and the
      vertebral arteries are common sites for thrombosis. The various channels that
      constitute collateral circulation in humans provide a margin of safety, so that
      in case of cerebral occlusion due to thrombosis, atherosclerosis, or vasospasm
      related to hemorrhage, blood supply to the affected area can be maintained
      through these collaterals. Collateral circulation is also present in rats.
      However, in rats, information on the presence of various types of aneurysms,
      their location and frequency in normal and experimental models of hypertension
      and stroke is still lacking. Cerebral arteries from humans and rats are
      characterized by the absence of external elastic lamina, as compared with
      systemic arteries. A type of multipolar cell resembling the interstitial cell of
      Cajal is present in the cerebral arteries of humans. Its function is unknown.
      Earlier reports of cerebral valves have been shown to represent intimal cushions
      near the branching points of the cerebral arteries. Intravascular bridges present
      in human cerebral arteries, have not been reported in rats. Finally, the presence
      of vascular remodeling, as found in the cerebral arterioles of hypertensive rats,
      remains to be established in the cerebral arterioles of human
      hypertensives.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7630928
TI  - Interactions between 5-hydroxytryptamine receptor subtypes: is a disturbed
      receptor balance contributing to the symptomatology of depression in humans?
AB  - The purpose of this review is to describe the consequences of antidepressant
      treatment on the behaviour of rodents after activation of serotonin (5
      hydroxytryptamine, 5-HT) receptor subtypes. In a summary table, the involvement
      of 5-HT receptors in inducing behavioural changes are described. It is emphasized
      that these effects are not always only exclusively linked to serotonergic
      functions nor that they are only initiated by central 5-HT receptors. Hereafter,
      the complex mutual inhibitory effects of 5-HT receptor subtype-mediated processes
      are discussed by interpreting effects of antagonists and describing the different
      effects of low and high doses of mixed 5-HT1C/5-HT2 receptor agonists. Mutual
      influences are seen particularly with 5-HT1A, 5-HT1C and 5-HT2, but not with 5
      HT1B, 5-HT1D or 5-HT3 receptor-mediated effects. It is shown that the behavioural
      consequences of 5-HT1A, 5-HT1C and 5-HT2 receptor stimulation may be changed by
      brain lesions or chronic treatment with drugs. Among these drugs are the
      antidepressants. Finally, 5-HT receptor function in depressed patients is
      discussed, and the hypothesis is proposed that an important function of
      antidepressants is to restore a disturbed balance between 5-HT1A, 5-HT1C and 5
      HT2 receptors in depressed patients.

PMID- 7630929
TI  - Gene-modified cells for the treatment of cancer.
AB  - Gene therapy involves the insertion of a gene into an organism to treat a
      disease. Since its early development in the 1970s, gene therapy has expanded
      rapidly both in terms of the methods available and the number of candidate
      diseases for treatment. This report reviews gene therapy for cancer, including
      methodology, pre-clinical studies and experimental clinical trials.

PMID- 7630930
TI  - Analogs of alkyllysophospholipids: chemistry, effects on the molecular level and
      their consequences for normal and malignant cells.
AB  - In the search for new approaches to cancer therapy, the first
      alkyllysophospholipid (ALP) analogs were designed and studied about two decades
      ago, either as potential immunomodulators or as antimetabolites of phospholipid
      metabolism. In the meantime, it has been demonstrated that they really act in
      this way. However, their special importance is based on the fact that, in
      addition, they interfere with key events of signal transduction, such as hormone
      (or cytokine)-receptor binding or processing, protein kinase C or phospholipase C
      function and phosphatidylinositol and calcium metabolism. There are no strict
      structural requirements for their activity. Differences in the cellular uptake or
      the state of cellular differentiation seem to be mainly responsible for higher or
      lower sensitivities of cells towards ALP analogs. Consequences of the molecular
      effects mentioned on the cellular level are cytostasis, induction of
      differentiation (while in contrast the effects of known inducers of
      differentiation such as 12-O-tetradecanoylphorbol-13-acetate are inhibited,
      probably as a consequence of protein kinase C inhibition) and loss of invasive
      properties. Already in sublytic concentrations, alterations in the membrane
      structure were observed, and lysis may begin at concentrations not much higher
      than those causing the other effects described. Few ALP analogs have already
      entered clinical studies or are in clinical use. ALP analogs are the only
      antineoplastic agents that do not act directly on the formation and function of
      the cellular replication machinery. Therefore, their effects are independent of
      the proliferative state of the target cells. Because of their interference with
      cellular regulatory events, including those failing in cancer cells, ALP analogs,
      beyond their clinical importance, are interesting model compounds for the
      development of new, more selective drugs for cancer therapy.

PMID- 7630931
TI  - Cholinergic neurotransmission studied in vivo using positron emission tomography
      or single photon emission computerized tomography.
AB  - During the past decade, considerable efforts have been made in the development of
      radiopharmaceuticals for the in vivo study of the cholinergic neurotransmission
      using positron emission tomography or single photon emission computerized
      tomography. The main cholinergic radioligands, labelled with positron- or gamma
      photon-emitting radionuclides, are reviewed with respect to use as in vivo
      markers of either acetylcholinesterase, vesicular acetylcholine transporter,
      brain and heart muscarinic receptors, or cholinergic nicotinic receptors. The
      main results obtained in the in vivo study of the physiology, pharmacology or
      pathology of the different steps of the cholinergic neurotransmission using
      single photon emission computerized tomography and positron emission tomography
      are discussed.

PMID- 7630932
TI  - Secondary cell-wall-specific glycoprotein(s) from French bean hypocotyls.
AB  - Specific labeling of secondary cell walls of tracheary elements and of xylary and
      phloem fibers has been observed when wheat germ agglutinin (WGA) and anti-WGA
      antibodies were used during ultrastructural studies of French bean (Phaseolus
      vulgaris L.) hypocotyls. In this report we demonstrate that at least part of this
      labeling is due to the presence of secondary cell-wall-specific glycoproteins.
      Three major novel glycoproteins with relative molecular weights of 55,000,
      86,000, and 90,000, purified by means of WGA-Sepharose affinity chromatography,
      have been characterized. Their amino acid composition indicates that they are not
      the members of known classes of structural cell-wall proteins, since they contain
      no hydroxyproline, a lower level of glycine than seen in glycine-rich proteins,
      and very little proline. N-terminal sequences of all three proteins show no
      significant homology with other proteins. Antibodies were raised against
      electrophoretically pure 90-kD glycoprotein. These were used to localize this
      protein in secondary cell walls of xylem tracheary elements and in xylary and
      phloem fibers, i.e. in the same compartments where labeling with WGA has been
      observed. To our knowledge this is one of the first biochemical and
      ultrastructural demonstrations of secondary cell-wall-specific glycoproteins.

PMID- 7630933
TI  - Effects of light and chloroplast functional state on expression of nuclear genes
      encoding chloroplast glyceraldehyde-3-phosphate dehydrogenase in long hypocotyl
      (hy) mutants and wild-type Arabidopsis thaliana.
AB  - In a previous study of Arabidopsis thaliana (J. Dewdney, T.R. Conley, M.-C. Shih,
      H.M. Goodman [1993] Plant Physiol 103: 1115-1121), it was postulated that both
      blue light receptor- and phytochrome-mediated pathways contribute to regulation
      of the nuclear genes encoding A and B subunits of glyceraldehyde-3-phosphate
      dehydrogenase (GAPA and GAPB). Here were report on the involvement of a nuclear
      gene encoding a putative blue-light receptor (HY4) and of a nuclear gene encoding
      phytochrome A apoprotein (PHYA) in regulation of the GAPA and GAPB genes in
      response to blue and far-red light. Continuous light irradiation experiments with
      the hy4 mutant demonstrate that the HY4 gene product is required for full
      expression of GAPA, GAPB, and one or more of the nuclear genes encoding small
      subunits of of ribulose-1,5-bisphosphate carboxylase/oxygenase. Continuous light
      irradiation and fluence-response studies with the phyA-101 mutant show that
      phytochrome A functions in far-red light regulation of GAPA, GAPB, nuclear genes
      encoding small subunits of ribulose-1,5-bisphosphate carboxylase/oxygenase, and
      CAB genes. Phytochromes A and B alone either do not participate in red light
      mediated gene regulation or have redundant functions, as shown by analysis of
      phyA-101 and phyB-1 single mutants. In addition, the hypothesis that chloroplast
      nucleus interactions affect GAPA and GAPB gene regulation was tested. Herbicide
      mediated photooxidative damage to chloroplasts in A thaliana seedlings strongly
      decreased the maximum amount of GAPA and GAPB steady-state mRNA detected in
      continuous-light irradiation experiments. Full expression of the GAPB genes is
      dependent on the presence of functional chloroplasts.

PMID- 7630934
TI  - A region of the Arabidopis Lhcb1*3 promoter that binds to CA-1 activity is
      essential for high expression and phytochrome regulation.
AB  - We have previously characterized a protein from Arabidopsis thaliana, called CA
      1, that bound to a specific region of the Lhcb1*3 promoter. This binding activity
      was of interest because the sequence to which it bound is included in a portion
      of the promoter that is sufficient for phytochrome regulation and because the
      activity was absent in photomorphogenic mutant det1 seedlings (L. Sun, R.A.
      Doxsee, E. Harel, E.M. Tobin [1993] Plant Cell 5: 109-121). We have now directly
      tested whether the nucleotide sequence to which CA-1 binds is required for
      regulation of the transcription of this gene by phytochrome. A mutation that
      abolished CA-1 binding in vitro was introduced into a 1.15-kb segment of the
      Lhcb1*3 promoter, and both the wild-type and mutant promoter fragments were fused
      to a uidA reporter gene and used to stably transform A. thaliana. Ten different
      homozygous lines were examined for phytochrome responsiveness for each of the two
      constructs by assaying beta-glucuronidase activity. The wild-type construct
      showed normal phytochrome responsiveness. The mutant construct showed no
      phytochrome response, and the overall level of beta-glucuronidase activity in
      etiolated seedlings was decreased by about 2 orders of magnitude. We did not
      detect a response to a B photoreceptor other than phytochrome itself for either
      the wild-type or mutant construct. We conclude that information essential for
      both a high level of expression and phytochrome responsiveness is contained in a
      27-bp region to which the CA-1 activity binds.

PMID- 7630935
TI  - Isolation and expression of three gibberellin 20-oxidase cDNA clones from
      Arabidopsis.
AB  - Using degenerate oligonucleotide primers based on a pumpkin (Cucurbita maxima)
      gibberellin (GA) 20-oxidase sequence, six different fragments of dioxygenase
      genes were amplified by polymerase chain reaction from arabidopsis thaliana
      genomic DNA. One of these was used to isolate two different full-length cDNA
      clones, At2301 and At2353, from shoots of the GA-deficient Arabidopsis mutant ga1
      2. A third, related clone, YAP169, was identified in the Database of Expressed
      Sequence Tags. The cDNA clones were expressed in Escherichia coli as fusion
      proteins, each of which oxidized GA12 at C-20 to GA15, GA24, and the C19 compound
      GA9, a precursor of bioactive GAs; the C20 tricarboxylic acid compound GA25 was
      formed as a minor product. The expression products also oxidized the 13
      hydroxylated substrate GA53, but less effectively than GA12. The three cDNAs
      hybridized to mRNA species with tissue-specific patterns of accumulation, with
      At2301 being expressed in stems and inflorescences, At2353 in inflorescences and
      developing siliques, and YAP169 in siliques only. In the floral shoots of the ga1
      2 mutant, transcript levels corresponding to each cDNA decreased dramatically
      after GA3 application, suggesting that GA biosynthesis may be controlled, at
      least in part, through down-regulation of the expression of the 20-oxidase genes.

PMID- 7630936
TI  - Organization of photosystem I polypeptides. Identification of PsaB domains that
      may interact with PsaD.
AB  - PsaA and PsaB are homologous integral membrane-proteins that form the
      heterodimeric core of photosystem i (PSI). We used subunit-deficient PSI
      complexes from the mutant strains of the cyanobacterium Synechocystis sp. PCC
      6803 to examine interactions between PsaB and other PSI subunits. Incubation of
      the wild-type PSI with thermolysin yielded 22-kD C-terminal fragments of PsaB
      that were resistant to further proteolysis. Modification of the wild-type PSI
      with N-hydroxysuccinimidobiotin and subsequent cleavage by thermolysin showed
      that the lysyl residues in the 22-kD C-terminal domain were inaccessible to
      modification by N-hydroxysuccinimidobiotin. The absence of PsaE, PsaF, PsaI,
      PsaJ, or PsaL facilitated accumulation of 22-kD C-terminal fragments of PsaB but
      did not alter their resistance to further proteolysis. When the PsaD-less PSI was
      treated with thermolysin, the 22-kD C-terminal fragments of PsaB were rapidly
      cleaved, with concomitant accumulation of a 16-kD fragment and then a 3.4-kD one.
      We mapped the N termini of these fragments by N-terminal amino acid sequencing
      and the C termini from their positive reaction with an antibody against the C
      terminal peptide of PsaB. The cleavage sites were proposed to be in the
      extramembrane loops on the cytoplasmic side. Western blot analyses showed
      resistance of PsaC and PsaI to proteolysis prior to cleavage of the 22-kD
      fragments. Therefore, we propose that PsaD shields two extramembrane loops of
      PsaB and protects the C-terminal domain of PsaB from in vitro proteolysis.

PMID- 7630938
TI  - Cis elements and trans-acting factors affecting regulation of a nonphotosynthetic
      light-regulated gene for chloroplast glutamine synthetase.
AB  - The glutamine synthetase (GS) gene family in pea (Pisum sativum) consists of four
      nuclear genes encoding distinct isoenzymes. Molecular studies have show that the
      GS2 gene encoding chloroplast-localized GS is expected in specific cell types and
      is regulated by diverse factors such as light and photorespiration. Here, we
      present the nucleotide sequence of the pea GS2 gene promoter. To identify the
      elements involved in regulation of GS2 expression, GS2 promoter-deletion analyses
      were performed using GS2-GUS fusions in tobacco (Nicotiana tabacum). This
      analysis revealed that the GS2 transit peptide is not required for mesophyll cell
      specific expression of beta-glucuronidase (GUS). GUS activity was induced 2- to 4
      fold in light-grown versus etiolated T1 seedlings. However, high levels of GUS
      activity were observed in etiolated seedlings. This observation demonstrated that
      regulation of expression of GS2, a nonphotosynthetic light-regulated gene,
      involves additional factors. A 323-bp GS2 promoter sequence is sufficient to
      confer light regulation to the GUS reporter gene in leaves of mature transgenic
      tobacco. Light-regulated expression of this pea gene promoter is observed in both
      tobacco and Arabidopsis, suggesting that the regulatory elements are conserved.
      Gel-shift analysis detected DNA-protein complexes formed with potential
      transcription elements within this short, light-responsive GS2 promoter fragment.

PMID- 7630937
TI  - Tomato exo-(1-->4)-beta-D-galactanase. Isolation, changes during ripening in
      normal and mutant tomato fruit, and characterization of a related cDNA clone.
AB  - An exo-(1-->4)-beta-D-galactanase was isolated from ripe tomato fruit
      (Lycopersicon esculentum Mill. cv Ailsa Craig and cv Better Boy) using anion
      exchange, gel filtration, and cation-exchange chromatography. Sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis of the most active fraction revealed a
      predominant protein band at 75 kD and several minor bands. A 30-amino acid N
      terminal sequence from this 75-kD protein showed a high degree of homology with
      other recently identified beta-galactosidase/ galactanase proteins from persimmon
      and apple fruits (I.-K. Kang, S.-G. Suh, K.C. Gross, J.-K. Byun [1994] Plant
      Physiol 105: 975-979; G.S. Ross, T. Wegrzyn, E.A. MacRae, R.J. Redgwell [1994]
      Plant Physiol 106: 521-528) and with the predicted polypeptide sequence encoded
      by the ethylene-regulated SR12 gene in carnation (K.G. Raghothama, K.A. Lawton,
      P.B. Goldsbrough, W.R. Woodson [1991] Plant Mol Biol 17: 61-71). The enzyme
      focused to a single band of beta-galactosidase activity on an isoelectrofocusing
      gel at pH 9.8. The enzyme was specific for (1-->4)-beta-D-galactan substrates
      with a pH optimum of 4.5. The only reaction product detected was monomeric
      galactose, indicating that the enzyme was an exo (1-->4)-beta-D-galactanase. beta
      Galactanase activity increased at the onset of ripening in normal fruit, but no
      similar increase was detected in the nonripening mutants nor and rin. A tomato
      homolog (pTombetagal1) was isolated using the SR12 cDNA clone from carnation as a
      probe. This clone showed 73% identify at the amino acid level with beta
      galactosidase-related sequences from apple and asparagus and 66% identity with
      SR12. pTombetagal1 is a member of a gene family. Northern analysis demonstrated
      that pTombetagal1 expression was ripening related in normal fruits, with lower
      levels apparent in the nonsoftening mutants.

PMID- 7630939
TI  - C4 isoform of NADP-malate dehydrogenase. cDNA cloning and expression in leaves of
      C4, C3, and C3-C4 intermediate species of Flaveria.
AB  - In C4 plants of the NADP-malic enzyme type, an abundant, mesophyll cell-localized
      NADP-malate dehydrogenase (MDH) acts to convert oxaloacetate, the initial product
      of carbon fixation, to malate before it is shuttled to the bundle sheath. Since
      NADP-MDH has different but important roles in leaves of C3 and C4 plants, we have
      cloned and characterized a nearly full-length cDNA encoding NADP-MDH from
      Flaveria trinervia (C4) to permit comparative structure/expression studies within
      the genus flaveria. The dicot genus Flaveria includes C3-C4 intermediate species,
      as well as C3 and C4 species. We show that the previously noted differences in
      NADP-MDH activity levels among C3, C4, and C3-C4 Flaveria species are in part due
      to interspecific differences in mRNA accumulation. We also show that the NADP-MDH
      gene appears to be present as a single copy among different Flaveria species,
      suggesting that a pre-existing gene has been reregulated during the evolution
      from C3 to C4 plants to accommodate the abundance and localization requirements
      of the C4 cycle.

PMID- 7630940
TI  - Peroxisomal copper, zinc superoxide dismutase. Characterization of the isoenzyme
      from watermelon cotyledons.
AB  - The biochemical and immunochemical characterization of a superoxide dismutase
      (SOD, EC 1.15.1.1) from peroxisomal origin has been carried out. The enzyme is a
      Cu,Zn-containing SOD (CuZn-SOD) located in the matrix of peroxisomes from
      watermelon (Citrullus vulgaris Schrad.) cotyledons (L.M. Sandalio and L.A. del
      Rio [1988] Plant Physiol 88: 1215-1218). The amino acid composition of the enzyme
      was determined. Analysis by reversed-phase high-performance liquid chromatography
      of the peroxisomal CuZn-SOD incubated with 6 M guanidine-HCl indicated that this
      enzyme contained a noncovalently bound chromophore group that was responsible for
      the absorbance peak of the native enzyme at 260 nm. The amino acid sequence of
      the peroxisomal CuZn-SOD was determined by Edman degradation. Comparison of its
      sequence with those reported for other plant SODs revealed homologies of about
      70% with cytosolic CuZn-SODs and of 90% with chloroplastic CuZn-SODs. The
      peroxisomal SOD has a high thermal stability and resistance to inactivation by
      hydrogen peroxide. A polyclonal antibody was raised against peroxisomal CuZn-SOD,
      and by western blotting the antibody cross-reacted with plant CuZn-SODs but did
      not recognize either plant Mn-SOD or bacterial Fe-SOD. The antiSOD-immunoglobulin
      G showed a weak cross-reaction with bovine erythrocytes and liver CuZn-SODs, and
      also with cell-free extracts from trout liver. The possible function of this CuZn
      SOD in the oxidative metabolism of peroxisomes is discussed.

PMID- 7630941
TI  - Posttranscriptional and posttranslational control of enolase expression in the
      facultative Crassulacean acid metabolism plant Mesembryanthemum Crystallinum L.
AB  - During the induction of Crassulacean acid and metabolism by environmental
      stresses in the common ice plant (Mesembryanthemum crystallinum L.), enzyme
      activities involved in glycolysis and gluconeogenesis, including enolase (2
      phospho-D-glycerate hydrolase), increase significantly. In this study, we
      describe two nearly identical cDNA clones (Pgh1a and Pgh1b) encoding enolase from
      the common ice plant. This cytoplasmically localized enzyme is encoded by a gene
      family of at least two members. The polypeptides encoded by these cDNAs share a
      high degree of amino acid sequence identity (86.7-88.3%) with other higher plant
      enolases. Enolase activity increased more than 4-fold in leaves during salt
      stress. This increase was accompanied by a dramatic increase in Pgh1
      transcription rate and the accumulation of enolase transcripts in leaves. Pgh1
      transcript levels also increased in leaves in response to low temperature,
      drought, and anaerobic stress conditions and upon treatment of unstressed plants
      with the plant growth regulators abscisic acid and 6-benzylaminopurine. In roots,
      enolase transcripts increased in abundance in response to salt, low and high
      temperature, and anaerobic stresses. Surprisingly, we observed no increase in
      enolase protein levels, despite the increased levels of mRNA and enzyme activity
      during salt stress. The stress-induced increase in enolase activity is therefore
      due to posttranslational regulation of steady-state enzyme pools. Our results
      demonstrate that the stress-induced shift to Crassulacean acid metabolism in the
      ice plant involves complex regulatory control mechanisms that operate at the
      transcriptional, posttranscriptional, and postranslational levels.

PMID- 7630942
TI  - Characterization of a cDNA encoding a novel heat-shock protein that binds to
      calmodulin.
AB  - A cDNA clone (pTCB48) encoding a calmodulin-binding protein was isolated by
      screening a lambda ZAPII cDNA expression library constructed from cell cultures
      of heat-shocked tobacco (Nicotiana tabacum L. cv Wisconsin-38) with metabolically
      labeled [35S]calmodulin. Calmodulin gel overlay analysis indicated that pTCB48
      generated major peptides of 53, 36, and 22 kD and two minor peptides of 37 and 16
      kD that bound calmodulin in a Ca(2+)-dependent manner. Deletion analysis of
      pTCB48 indicated that these and the minor calmodulin-binding proteins resulted
      from the insert. A probe made from the cDNA insert recognized two bands with
      sizes of 2.1 and 1.8 kb on northern blot analysis. Both species of RNAs were
      undetectable in the control and were induced after 15 min of heat-shock treatment
      at 38 degrees C. The intensity of the two bands reached maximum after 1.5 h of
      heat-shock treatment. The cDNA clone was not full length; however, the complete
      sequence was determined by 5' rapid amplification of cDNA ends using nested
      antisense primers. The full-length cDNA contains 1648 bp and a single open
      reading frame of 1347 bp and is expected to encode a protein of approximately 50
      kD. No significant homology with other reported genes and proteins was found.
      Structural predictions, deletion analysis, and gel overlay analysis suggested
      that the calmodulin-binding domain was a basic amphiphilic alpha-helix near the C
      terminus of the protein. The strong induction of the mRNA for this protein
      suggests a role for Ca2+/calmodulin-mediated process in the heat-shock response.

PMID- 7630943
TI  - Purification of NAD-dependent mannitol dehydrogenase from celery suspension
      cultures.
AB  - Mannitol dehydrogenase, a mannitol:mannose 1-oxidoreductase, constitutes the
      first enzymatic step in the catabolism of mannitol in nonphotosynthetic tissues
      of celery (Apium graveolens L.). Endogenous regulation on the enzyme activity in
      response to environmental cues is critical in modulating tissue concentration of
      mannitol, which, importantly, contribute to stress tolerance of celery. The
      enzyme was purified to homogeneity from celery suspension cultures grown on D
      mannitol as the carbon source. Mannitol dehydrogenase was purified 589-fold to a
      specific activity of 365 mumol h-1 mg-1 protein with a 37% yield of enzyme
      activity present in the crude extract. A highly efficient and simple purification
      protocol was developed involving polyethylene glycol fractionation,
      diethylaminoethyl-anion-exchange chromatography, and NAD-agarose affinity
      chromatography using NAD gradient elution. Sodium dodecylsulfate gel
      electrophoresis of the final preparation revealed a single 40-kD protein. The
      molecular mass of the native protein was determined to be approximately 43 kD,
      indicating that the enzyme is a monomer. Polyclonal antibodies raised against the
      enzyme inhibited enzymatic activity of purified mannitol dehydrogenase.
      Immunoblots of crude protein extracts from mannitol-grown celery cells and sink
      tissues of celery, celeriac, and parsley subjected to sodium dodecyl sulfate gel
      electrophoresis showed a single major immuno-reactive 40-kD protein.

PMID- 7630944
TI  - Identification of a plant-encoded analog of PKR, the mammalian double-stranded
      RNA-dependent protein kinase.
AB  - Plant virus or viroid infection stimulates the phosphorylation of a plant-encoded
      protein of M(r) 68,000 to 70,000 (now termed pPKR) that is associated with double
      stranded RNA-stimulated protein kinase activity. Using various biochemical and
      immunological comparisons, we have demonstrated that this plant protein is an
      analog of the mammalian PKR enzymes. pPKR is both cytosolic and ribosome
      associated, similar to mammalian PKR, and appears to be capable of
      phosphorylating exogenous histones. Monoclonal anti-serum to the human PKR as
      well as antiserum to a conserved double-stranded RNA-binding domain present on
      mammalian PKR demonstrated cross-reactivity with pPKR. Likewise, polyclonal
      antiserum to the pPKR detected the mouse and human PKR in western blot analysis.
      Northern blot analysis of a mammalian PKR cDNA detected a specific 2.5-kb
      transcript present in plant poly (A)+ RNA.

PMID- 7630945
TI  - Nucleotide sequence of a cDNA from Atriplex canescens (Pursh.) Nutt. A homolog of
      a jasmonate-induced protein from barley.

PMID- 7630946
TI  - The Ivr 1 gene for invertase in maize.

PMID- 7630947
TI  - Cloning and characterization of an anaerobically induced cDNA encoding glucose-6
      phosphate isomerase from maize.

PMID- 7630948
TI  - Cloning of a nuclear-encoded photosystem I gene, psaEb, in Nicotiana sylvestris.

PMID- 7630949
TI  - A maize acetyl-coenzyme A carboxylase cDNA sequence.

PMID- 7630950
TI  - Cloning and sequence of a cDNA encoding phenylalanine ammonia-lyase from the
      tropical forage legume Stylosanthes humilis.

PMID- 7630951
TI  - Nucleotide sequence of a cationic peroxidase gene from the tropical forage legume
      Stylosanthes humilis.

PMID- 7630952
TI  - The two psbA genes from the thermophilic cyanobacterium Synechococcus elongatus.

PMID- 7630954
TI  - A gene encoding a cinnamyl alcohol dehydrogenase homolog in Arabidopsis thaliana.

PMID- 7630955
TI  - A 1.7-kilobase genomic fragment of alfalfa DNA contains the lectin gene Mslec1.

PMID- 7630956
TI  - A cDNA encoding starch branching enzyme I from maize endosperm.

PMID- 7630957
TI  - Cloning and sequencing analysis of a full-length cDNA encoding a G protein alpha
      subunit, SGA1, from soybean.

PMID- 7630953
TI  - Three cDNAs encoding S-adenosyl-L-methionine synthetase from Actinidia chinensis.

PMID- 7630958
TI  - Nucleotide sequence of a cDNA for the maize protein synthesis initiation factor
      4A.

PMID- 7630959
TI  - Nucleotide sequence of a cDNA encoding the small subunit of ribulose-1,5
      bisphosphate carboxylase/oxygenase from Aegilops squarrosa.

PMID- 7630960
TI  - Molecular cloning of the gene encoding the L-asparaginase gene of Arabidopsis
      thaliana.

PMID- 7630961
TI  - Pummelo fruit transcript homologous to ripening-induced genes.

PMID- 7630962
TI  - Isolation and characterization of a cDNA for spinach cytosolic ascorbate
      peroxidase.

PMID- 7630963
TI  - The cox1 initiation codon is created by RNA editing in potato mitochondria.

PMID- 7630964
TI  - Maize phytoene desaturase maps near the viviparous5 locus.

PMID- 7630965
TI  - Nucleotide sequence of a cDNA from Lithospermum erythrorhizon homologous to PR-1
      of parsley.

PMID- 7630966
TI  - The large subunit of the embryo isoform of ADP glucose pyrophosphorylase from
      maize.

PMID- 7630967
TI  - Isolation and characterization of an oilseed rape fructose-1,6-bisphosphatase
      cDNA.

PMID- 7630968
TI  - Sequence and regulation of a late embryogenesis abundant group 3 protein of
      maize.

PMID- 7630969
TI  - A cDNA clone for isocitrate lyase from tomato.

PMID- 7630970
TI  - Repair of DNA damage induced by ultraviolet radiation.

PMID- 7630971
TI  - Flavonol 3-O-glycosyltransferases associated with petunia pollen produce
      gametophyte-specific flavonol diglycosides.
AB  - Wild-type petunia pollen accumulates high levels of flavonol 3-O-glycosides.
      Pollen from conditionally male-fertile petunia has no flavonols and is unable to
      germinate. Pollen function is restored both in vivo and in vitro by providing
      flavonol aglycones, but not flavonol glycosides, to the pollen. In the present
      study, incubation of an in vitro suspension of conditionally male-fertile pollen
      with kaempferol or quercetin resulted in the accumulation of kaempferol and
      quercetin 3-O-glycosides in the pollen. We identified two glycosyltransferase
      activities associated with the intact pollen grain that catalyze the formation of
      a gametophyte-specific class of flavonol glycosides. Feeding studies showed that
      product formation was highly specific for flavonols with an unsubstituted 3
      hydroxyl group and was not dependent on an external source of UDP-hexose.
      Ultraviolet spectral analysis, fast atom bombardment mass spectrometry, 1H
      nuclear magnetic resonance, and 13C-nuclear magnetic resonance identified the
      products as kaempferol and quercetin 3-O-(2"- O-beta-D-glucopyranosyl)-beta-D
      galactopyranoside, identical with the flavonol 3-O-glycosides present in wild
      type pollen. The sugars are linked in a 1-->2 configuration that results in a
      pollen-specific class of compounds. To retain both glycosyltransferase activities
      in a cell-free extract, it was necessary to add triton X-100, suggesting that one
      or both of the proteins may be associated with a pollen membrane. A model for
      flavonol glycoside biosynthesis and uptake into the pollen is discussed in terms
      of the germination requirement for flavonols.

PMID- 7630973
TI  - Activation of two osmotin-like protein genes by abiotic stimuli and fungal
      pathogen in transgenic potato plants.
AB  - Osmotin-like proteins are encoded by at least six members of a multigene family
      in Solanum commersonii. A genomic clone (lambda pGEM2a-7) that contains two
      osmotin-like protein genes (OSML13 and OSML81) arranged in the same
      transcriptional orientation has been isolated. Restriction mapping and sequence
      analysis indicated that the two intronless genes correspond to the previously
      characterized pA13 and pA81 cDNAs. To study the transcriptional activation of
      OSML13 and OSML81 promoters, the 5' flanking DNA sequence (-1078 to +35 of OSML13
      and -1054 to +41 of OSML81) was fused to the beta-glucoronidase (GUS) coding
      region, and the chimeric gene fusions were introduced into wild potato (S.
      commersonii) plants via Agrobacterium-mediated transformation. Analysis of the
      chimeric gene expression in transgenic potato plants showed that both 5' flanking
      DNA sequences are sufficient to impart GUS inducibility by abscisic acid, NaCl,
      salicylic acid, wounding, and fungal infection. Low temperature activated both
      chimeric genes only slightly. Infection with Phytophthora infestans resulted in
      strong GUS expression from both chimeric genes primarily in the sites of pathogen
      invasion, suggesting a limited diffusion of fungal infection-mediated signals.
      The expression patterns of both osmotin-like protein genes implicate their dual
      functions in osmotic stress and plant pathogen defense.

PMID- 7630974
TI  - SPR Award, 1994. For distinguished contributions to psychophysiology: Emanuel
      Donchin.

PMID- 7630972
TI  - The soybean GH2/4 gene that encodes a glutathione S-transferase has a promoter
      that is activated by a wide range of chemical agents.
AB  - Transcriptional activation of the soybean (Glycine max) GH2/4 gene (also referred
      to as Gmhsp26-A) and increase in abundance of the GH2/4 mRNA (also referred to as
      pCE54) have been previously shown to occur following treatment of soybean
      seedlings with auxins, nonauxin analogs, heavy metals, and a variety of other
      agents. To determine whether the GH2/4 promoter is responsive to an array of
      different agents, we have analyzed the inducibility of the GH2/4 promoter fused
      to the beta-glucuronidase reporter gene in transgenic tobacco (Nicotiana tabacum)
      plants. We have shown that a wide variety of chemical agents induce this promoter
      in a tissue-specific and concentration-dependent manner. In addition, we have
      used an affinity-purified antibody raised against recombinant GH2/4 protein to
      show that the GH2/4 protein increases in response to auxin application and is
      localized in the cytosol of soybean cells. Recombinant GH2/4 protein can be
      purified to homogeneity on a glutathione-agarose resin, and the purified protein
      has glutathione S-transferase activity when assayed with the substrate 1-chloro
      2,4-dinitrobenzene.

PMID- 7630975
TI  - Selective processing of two-dimensional visual stimuli in young and old subjects:
      electrophysiological analysis.
AB  - In this study, we compared selection of conjunctions of spatial frequency and
      orientation in young and old subjects, using performance and event-related brain
      potential (ERP) measures. Responses to target conjunctions were slightly but
      significantly slower in older subjects; lateralized readiness potential (LRP)
      onsets did not differ between groups. Older subjects made more false-positive
      responses to stimuli sharing only spatial frequency with the target. Difference
      waves associated with selection of separate dimensions included frontal
      positivity and occipital and central negativity and were 20-50 ms slower in older
      subjects. Later parts of these difference waves had smaller amplitudes in older
      subjects. Sensory discrimination, assessed through the effects of physical
      stimulus parameters on ERPs, was not clearly affected by age. Data are
      interpreted in terms of a relationship in older subjects between longer latencies
      of difference waves but equal LRP onsets and a higher false-alarm rate.

PMID- 7630976
TI  - Event-related potentials to airway occlusion in young and old subjects.
AB  - Event-related potentials (ERPs) were recorded to both inspiratory and expiratory
      airway occlusion in young (21-28 years) and old (55-67 years) subjects under both
      attend and ignore conditions. Early and late components of the ERP (N1, P2, N2,
      P3) were observed to both types of occlusions in both conditions. Variations in
      these components were consistent in both direction and degree with those observed
      in oddball tasks employing exteroceptive stimuli. ERPs for breathing may serve to
      clarify sensory attributes of respiratory stimuli in humans and to identify
      central processing abnormalities in patient populations.

PMID- 7630977
TI  - Abnormality of smooth pursuit eye movement initiation: specificity to the
      schizophrenia spectrum?
AB  - Schizophrenia patients have a deficiency of smooth pursuit eye movement
      initiation. We addressed whether this deficit is specifically related to a
      predisposition for schizophrenia. Thirty-two relatives of schizophrenia patients,
      eight schizotypals, 13 psychiatric comparison, and 33 nonpsychiatric subjects
      were assessed on smooth pursuit initiation. The nonpsychiatric subjects had
      significantly higher eye accelerations than did subjects in the other three
      groups, who did not significantly differ. The relatives were subdivided into
      three groups: (a) those with a schizophrenia spectrum disorder (n = 4) performed
      similarly to the schizotypals; (b) those with a major depression history (n = 7)
      were similar to the psychiatric comparison subjects; and (c) those with no
      psychiatric history differed from the nonpsychiatric subjects only on 30
      degrees/s targets. There was also a significant relationship between offspring
      and parent eye accelerations to 30 degrees/s targets (r = .476). These results
      suggest that pursuit initiation deficits may be associated with a nonspecific,
      genetically transmitted neurological abnormality among schizophrenia spectrum
      disorder subjects.

PMID- 7630978
TI  - Patterns of cerebral activation while mental images are rotated and changed in
      size.
AB  - Event-related brain potentials were recorded while subjects performed either a
      rotation or a size scaling transformation of a mental image. Images had to be
      rotated 0 degrees, 60 degrees, or 120 degrees or their size had to be enlarged by
      factors of 1:1, 1:3, or 1:5. Both tasks were accompanied by pronounced negative
      slow potentials, which extended over several seconds. The relative maximum of
      these shifts emerged at central to occipital leads. Over the occipital cortex,
      the negative potential had a similar amplitude level in all conditions and both
      tasks. However, at parietal and central areas, the negative slow wave changed in
      relation to the difficulty of the task. The amplitude increased with increasing
      rotation demands and if the scaling operation required an exact computation of
      the coordinates of the image. None of these effects could be attributed to an
      inverse change of P300.

PMID- 7630979
TI  - Startle reflex modulation during exposure to pleasant and unpleasant odors.
AB  - The eyeblink component of the startle response to acoustic probes was measured
      while subjects smelled pleasant odors, unpleasant odors, or no odor. Peak
      electromyogram (EMG) 20-90 ms after probe onset was greater during unpleasant
      than during no odor conditions; EMGs for pleasant odors did not differ from those
      for no odor. Base tension in orbicularis oculi muscles was also higher during
      unpleasant odors. The results for unpleasant odors parallel those found in
      previous studies that have used a variety of methods for producing negatively
      valenced experiences. The results for pleasant odors diverge from those of most
      previous studies, which have found startle attenuation during positively valenced
      experiences. However, the results may be compatible with the suggestion (Lang,
      Bradley, & Cuthbert, 1992) that the motivational state that modulates startle
      involves both valence and arousal. Pleasant odors may require appropriate
      contexts to produce the positive motivational state required for startle
      attenuation.

PMID- 7630980
TI  - Acoustic startle and anticipatory anxiety in humans: effects of monaural right
      and left ear stimulation.
AB  - The startle reflex elicited by binaural acoustic startle stimuli is potentiated
      by the threat of electric shock. The present study explored the lateralization of
      this fear-potentiated startle reflex effect using acoustic startle stimuli
      delivered binaurally or monaurally to the left or right ear and recorded from the
      left and right orbicularis oculi muscles. Consistent with previous results, the
      acoustic startle to binaural stimulation was potentiated during the anticipation
      of shock. This effect was also present for monaural stimulation but was greater
      when startle stimuli were delivered to the right than to the left ear. The
      results are discussed in terms of hemispheric lateralization during shock
      anticipation.

PMID- 7630981
TI  - The metrics of cardiac chronotropism: biometric perspectives.
AB  - The selection of heart period versus heart rate as a chronotropic metric has been
      considered from quantitative and statistical perspectives, which have not yielded
      a universal preference for either metric. In the present paper, we discuss
      biometric considerations that bear on the selection of the optimal chronotropic
      metric. Biometric evidence reveals that the transfer functions relating autonomic
      nerve traffic to chronotropic effects on the heart are more nearly linear for
      heart period than for heart rate. This confers considerable advantage on heart
      period as a chronotropic metric and can facilitate the study of
      psychophysiological relationships. We further show that heart period offers
      greater flexibility, because heart period data can be evaluated in cardiac time
      units (beats) or in real-time units (s), whereas heart rate data can only be
      analyzed in real time. These considerations suggest clear advantages to heart
      period as a chronotropic metric.

PMID- 7630982
TI  - Cardiovascular effects of experimentally induced efficacy (ability) appraisals at
      low and high levels of avoidant task demand.
AB  - Subjects were led to believe they had low or high ability with respect to a
      scanning task and then given the chance to avoid a noise by attaining a low
      (easy) or high (difficult) standard on a version of the task. Performance period
      measurements indicated that heart rate reactivity was greater in the difficult
      than easy condition for high-ability subjects but greater in the easy than
      difficult condition for low-ability subjects. Furthermore, whereas heart rate
      responses tended to be greater for low- than for high-ability subjects when the
      standard was low, they were greater for high- than for low-ability subjects when
      the standard was high. Results for blood pressure reactivity were comparable,
      although pairwise comparisons were not as consistently reliable. The main
      findings conceptually replicate and extend effects from previous studies; they
      also call further into question conventional conceptions that intimate an inverse
      relation between perceived self-efficacy and physiologic responsivity in the face
      of threat.

PMID- 7630983
TI  - Auditory and visual semantic priming using different stimulus onset asynchronies:
      an event-related brain potential study.
AB  - Semantic priming effects (behavioral and electrophysiological) were compared in
      the visual and auditory modalities across three stimulus onset asynchronies
      (SOAs; 0, 200, and 800 ms). When both prime and target were presented in the
      visual modality (the prime just to the left of a fixation point and the target to
      the right), there were N400 priming effects present across the three SOAs.
      However, the N400 in the 0-ms SOA condition extended longer in time (800 vs. 500
      ms) than in the other SOAs. When both the prime and target were presented in the
      auditory modality (the prime to the right ear and the target to the left), the
      largest priming effects were found for the 800-ms SOA. Moreover, there was a
      relatively early priming effect present in the 0- and 800-ms SOA conditions but
      not in the 200-ms condition. The results are discussed in terms of modality
      differences in the time course of word comprehension processes.

PMID- 7630984
TI  - Temporal stability of heart period variability during a resting baseline and in
      response to psychological challenge.
AB  - Central to the psychophysiologic reactivity hypothesis of the etiology of
      coronary artery disease is the assumption that reactivity is an individual
      characteristic that is stable over time. Although heart rate (HR) and blood
      pressure reactivity appear to meet this criterion, temporal stability of cardiac
      autonomic control as measured by analysis of heart period variability (HPV) has
      not been assessed. In this study, we tested the stability of HPV, measured in
      both the time and frequency domain, during a quiet, resting baseline and in
      response to 5-min mental arithmetic and reaction time tasks, in 20 normal
      subjects measured in three testing sessions during a 9-month period. Stability,
      assessed by the intraclass correlation coefficient (ICC), was excellent for
      resting baseline measures of HR and HPV, with ICCs of 0.68-0.86. However, HR and
      HPV reactivity to either arithmetic or reaction time tasks generally was less
      stable, with ICCs of 0.17-0.73, in contrast to results of previous studies
      demonstrating long-term stability of HR responses to psychological challenge.
      Stability of aggregated reactivity scores was only slightly improved. Whether for
      individual tasks or aggregated measures, reactivity of total and low-frequency
      measures of HPV was moderately stable but stability of high-frequency HPV
      reactivity was poor.

PMID- 7630985
TI  - Letter from South Africa.

PMID- 7630986
TI  - More surveillance in child care, please!

PMID- 7630987
TI  - Public health surveillance in child-care settings.
AB  - To investigate the potential contribution of public health surveillance systems
      to the health of children and workers in out-of-home child-care settings, we
      review existing public health surveillance practice in the United States. We
      identify issues that are of particular concern for surveillance in child-care
      settings. We propose a framework for developing public health surveillance
      systems that uses sentinel child-care sites, notifiable disease surveillance,
      modification of existing surveillance systems, and population surveys. Successful
      surveillance in these settings depends on the active participation of child-care
      providers, public health practitioners, and clinicians in (a) the selection of
      high priority diseases and injuries for surveillance; (b) the development of
      practical case definitions; (c) the augmentation of current surveillance systems
      to include disease and injury related to child care; and (d) the implementation,
      assessment, dissemination, and evaluation of new approaches for surveillance in
      child-care settings.

PMID- 7630988
TI  - Evaluation of California's statewide implementation of enhanced perinatal
      services as Medicaid benefits.
AB  - The authors evaluated enhanced perinatal services developed by public health
      specialists that were implemented statewide through specially certified Medicaid
      providers to find out whether they were as effective as those services originally
      tested in the public health agency's pilot project, and more effective than
      services from regular Medicaid providers. Multivariate logistic regression
      analyses yielded adjusted odds ratios of use of care and health outcome measures
      for the statewide services compared with both the pilot project and routine
      Medicaid care. Although women receiving the enhanced services implemented
      statewide did not return for prenatal visits as well as those in the pilot
      project, they did better than women with routine Medicaid providers. Women who
      kept at least the eight prenatal visits recommended by the Public Health Service
      in 1989 had risks of low weight births no different from those in the pilot
      project and significantly better than those for women with at least eight visits
      with routine Medicaid providers (adjusted odds ratio 0.70 with a 95 percent
      confidence interval from 0.54 to 0.91). Thus, there is evidence for the efficacy
      of the services, but additional improvement could be realized through improving
      the use of care.

PMID- 7630991
TI  - Evaluating false positives in two hospital discharge data sets of the Birth
      Defects Monitoring Program.
AB  - The principal goal in this study was to quantify false positives in the hospital
      discharge data of the Birth Defects Monitoring Program conducted by the Centers
      of Disease Control and Prevention. The two hospital data processing agencies
      which contribute data to the Birth Defects Monitoring Program, the Commission on
      Professional and Hospital Activities and the McDonnell Douglas Health Information
      Systems, had respective levels of false positives of 13.2 percent and 8.5
      percent, levels which were statistically different from each other. These false
      positive levels should be considered minimal because these data bases do not
      include information on sick babies who may be transferred into or out of member
      hospitals, and who may have their initial diagnoses significantly modified.
      Potential correlates of false positives were evaluated, including hospital size,
      diagnostic certainty, race, sex, and insurance source. Two-thirds of all false
      positives were due to the miscoding of correctly diagnosed anomalies, and another
      quarter were clearly contradicted in notes easily available before the patients
      were discharged. The authors hope that this study of false positives will enhance
      the interpretation of the Birth Defects Monitoring Program data and lead to
      improved understanding of data collection and processing.

PMID- 7630990
TI  - Office visits to ophthalmologists and other physicians for eye care among the
      U.S. population, 1990.
AB  - Despite growth in the use of ophthalmologic care in the last decade, little is
      known about the use of eye care services and patterns of physician contact across
      population subgroups. As the U.S. population grows older, such information is
      crucial in planning strategies for treatment and prevention of eye disorders as
      well as in identifying potential problems in access and use of eye care. Using
      the 1990 National Ambulatory Medical Care Survey data, a descriptive statistical
      analysis was employed to profile the possible variations in eye care-related
      office visits to ophthalmologists and other physicians across demographic groups.
      In 1990, a total of 49.3 million visits that were related primarily to an ocular
      disorder were made to physicians' offices; 43.8 million (89 percent) of these
      were visits to ophthalmologists and 5.4 million (11 percent) to other physicians.
      Use of ambulatory eye care varied across demographic subgroups. Those ages 65 or
      older had a substantially higher rate of eye care related outpatient visits per
      1,000 persons per year compared with the rest of the population (743.6 per 1,000
      versus 118.5 per 1,000, P < 0.001). Women had a higher rate than men (216.0 per
      1,000 versus 177.0 per 1,000, 0.01; P < 0.05). Blacks had a substantially lower
      rate than whites (143.2 per 1,000 versus 194.6 per 1,000, 0.001; P < 0.01). Those
      who visited ophthalmologists' offices also differed from those who visited other
      physicians' offices in terms of their age, sex, race, health insurance status,
      and disease characteristics. It is important to devote increased attention to the
      prevention of vision loss among the population groups that have a higher risk of
      developing eye diseases and that also may have underused or have less access to
      care. Results from this analysis, in combination with data on the prevalence of
      ocular disorders for different population groups, provide useful information to
      identify these high-risk groups.

PMID- 7630989
TI  - An overview of the effectiveness and efficiency of HIV prevention programs.
AB  - Because of the enormity of the HIV-AIDS epidemic and the urgency for preventing
      transmission, HIV prevention programs are a high priority for careful and timely
      evaluations. Information on program effectiveness and efficiency is needed for
      decision-making about future HIV prevention priorities. General characteristics
      of successful HIV prevention programs, programs empirically evaluated and found
      to change (or not change) high-risk behaviors or in need of further empirical
      study, and economic evaluations of certain programs are described and summarized
      with attention limited to programs that have a behavioral basis. HIV prevention
      programs have an impact on averting or reducing risk behaviors, particularly when
      they are delivered with sufficient resources, intensity, and cultural competency
      and are based on a firm foundation of behavioral and social science theory and
      past research. Economic evaluations have found that some of these behaviorally
      based programs yield net economic benefits to society, and others are likely cost
      effective (even if not cost-saving) relative to other health programs. Still,
      specific improvements should be made in certain HIV prevention programs.

PMID- 7630992
TI  - Measles reporting completeness during a community-wide epidemic in inner-city Los
      Angeles.
AB  - A study was undertaken to determine the extent of measles underreporting among
      preschool-age children. In two community surveys conducted in inner-city Los
      Angeles during 1990 and 1991, respondents were asked whether preschool-age
      children in their households had ever been ill with measles. Information about
      measles episodes was obtained and medical records were reviewed, when available.
      A probable measles case was defined as having 3 or more days of rash with fever
      of 38.3 degrees centigrade or greater, and either cough, coryza, or
      conjunctivitis. To determine the proportion of cases reported, probable measles
      cases identified were matched with measles cases reported to the Los Angeles
      County Department of Health Services. Of the 947 children ages 6 weeks through 59
      months included in the surveys, 35 children had experienced an illness episode
      which met the probable measles case definition. Ten (29 percent) of the 35
      probable measles cases were reported to the health department. Hospitals reported
      9 (69 percent) of 13 probable measles cases evaluated while private physicians'
      offices reported 0 (0 percent) of 12 evaluated (Fisher's exact test, P < 0.001),
      although 5 children were seen by private physicians before rash onset. Reporting
      was more complete for cases occurring during 1990 and 1991 (33 percent) than from
      1987 through 1989 (18 percent). The hospitalization rate for preschool-age
      children with probable measles cases in the catchment area was estimated to be 8
      percent (95 percent confidence interval = 0 to 18 percent). Although measles is a
      serious communicable disease which is almost completely preventable, cases of it
      among preschool-age children in this high incidence area were substantially
      underreported,especially by private physicians. Due to reporting bias, reported
      measles cases were representative of more severe cases than all the cases that
      occurred.

PMID- 7630993
TI  - Barriers to condom use and needle cleaning among impoverished minority female
      injection drug users and partners of injection drug users.
AB  - This study was undertaken to describe sexual behaviors and drug use and other
      factors that inhibit condom use and needle cleaning among impoverished women who
      are injection drug users (IDUs) or sexual partners of IDUs. This study also
      investigated whether risky sexual behavior or barriers to risk reduction differ
      with ethnicity and level of acculturation. Survey instruments to assess drug and
      sexual activity were administered to 378 African American and Latina women
      recruited primarily from homeless shelters and drug recovery programs. The most
      commonly cited barriers to condom use were belief that partners did not have
      acquired immunodeficiency syndrome (AIDS), lack of knowledge about where to get
      and how to use condoms, and discomfort discussing condom use with partners.
      African American women were more likely to report having multiple partners and
      unprotected sex, and more likely to report barriers in using, discussing, and
      obtaining condoms. Latina women were more likely to report partners' dislike of
      condoms. African American and highly acculturated Latina women were more likely
      to be IDUs than less acculturated Latina women. The most pervasive barriers for
      needle cleaning were not having personal needles, being high and not interested
      in needle cleaning, and not having disinfectant available. In a multiple logistic
      regression analysis for engaging in unprotected sex and cleaning needles, not
      ethnic or acculturation differences were found after controlling for selected
      demographic characteristics and risk factors. The data indicate a need to
      increase the supply of free or low cost condoms, to provide easily accessible
      sites for obtaining condoms, to supply clean needles,and to focus counseling for
      women on negotiating condom use with partners and the skillful and correct
      placement of the condom.

PMID- 7630994
TI  - The 90-Second Intervention: a patient compliance mediated technique to improve
      and control hypertension.
AB  - Hypertension, a leading risk factor for cardiovascular and renal diseases, occurs
      in up to 50 million Americans. Despite mounting evidence of the effectiveness of
      prevention and treatment, physicians are still unable to get their patients to
      adopt and adhere to treatment protocols. This project presents an innovative
      approach to compliance which is based on general systems theory and its
      applications in family therapy. The "90-Second Intervention" ("90 SI")
      incorporates the use of family and friends; it utilizes the therapeutic
      relationship or alliance of the physician-patient; and it embraces the well
      established fact that social support plays a key role in promoting health,
      decreasing susceptibility to disease, and facilitating recovery from illness. The
      physician asks the patients to identify who in their life loves or cares for them
      and would help them adhere to the treatment protocol. To implement the "90 SI,"
      the physician instructs the patient to telephone, in his or her presence, the
      identified helper(s) who then agree to support the patients' medical regimen.
      Specifically, the "90 SI" seeks to create a context to support the patients in a
      regimen of low to moderate intensity exercise, which is proven to be a powerful,
      cost-effective, and safe treatment. Patients who are identified with new onset or
      uncontrolled hypertension at three clinics in urban Philadelphia are the target
      population.

PMID- 7630995
TI  - What incentives are effective rewards for 'hidden populations' interviewed as a
      part of research projects?

PMID- 7630996
TI  - Community-based breast cancer intervention program for older African American
      women in beauty salons.
AB  - African American women are at high risk for morbidity and mortality from breast
      cancer. African American women ages 50 and older have been a difficult group to
      reach through conventional breast cancer intervention programs. Cultural and
      health beliefs that differ from mainstream society are reported to be factors
      contributing to the low rates of breast screening among this group. In addition
      to these attitudinal factors, older African American women are disproportionately
      represented among uninsured and under-insured Americans. As a result, cost
      becomes a barrier to mammography screening for many of these women. This project
      proposes to increase breast cancer screening awareness and provide a referral or
      free breast screening, or both, for African American women ages 50 and older.
      This information will be offered in the culturally familiar setting of local
      beauty salons. The culturally sensitive educational pamphlets developed by the
      National Cancer Institute (NCI) and video developed by the NCI-funded project,
      Cancer Prevention Research Unit, will be used to promote mammography, clinical
      breast examinations, and breast self-examination. Providers staffing a mobile
      mammography van provided by Dr. Anitha Mitchell of the Association of Black Women
      Physicians through a grant from the Breast and Cervical Cancer Control Program,
      funded by the Centers for Disease Control and Prevention, will perform mammograms
      for women on site during scheduled intervals. A followup telephone survey will be
      conducted.

PMID- 7630997
TI  - The health corner: a community-based nursing model to maximize access to primary
      care.
AB  - America spends more than $700 billion per year on a health care system that is
      unparalleled in the technological advances it produces, yet many Americans do not
      receive the basic health care they need. Access to obtaining these health
      services can be affected by economic, structural, or personal barriers. This
      paper describes a primary health care delivery that addresses the specific health
      concerns of a neighborhood. The model forges a partnership with the community
      while developing collaborative relationships with area health providers. Targeted
      health services are offered in a community-based, nurse-managed site. Clients
      receive the basic health services they need, local providers expand their client
      base with "satellite locations," and the major medical institutions receive more
      appropriate referrals and have less unnecessary use of the emergency rooms.

PMID- 7630998
TI  - Dance for health: improving fitness in African American and Hispanic adolescents.
AB  - Cardiovascular disease begins early in life but might be prevented or delayed by
      primary prevention programs designed for children and adolescents. Regular
      physical activity is an important part of primary prevention programs, and school
      physical education programs have potential for the promotion of regular physical
      activity. Cardiovascular disease is the major cause of death among Hispanics and
      African Americans in the United States. Low levels of fitness and increased body
      mass index are common in African American and Hispanic adolescents. Increased
      physical activity and the adoption of healthy eating habits would increase
      fitness and reduce body mass index among these adolescents. The purpose of the
      study was to undertake a small-scale controlled trial to determine if Dance for
      Health, an intervention program designed to provide an enjoyable aerobic program
      for African American and Hispanic adolescents, has a significant effect on
      improving aerobic capacity, helping students maintain or decrease weight, and on
      improving attitudes toward physical activity and physical fitness. In the first
      year of the program (1990-91), approximately 110 boys and girls ages 10-13 years
      participated in an aerobic dance pilot program three times per week for 12 weeks.
      Dance for Health was revised and continued in the 1992-93 school year with
      seventh grade students and an added culturally sensitive health curriculum. Forty
      three students were randomized to Dance for Health and 38 to usual physical
      activity. Those in the intervention class received a health education curriculum
      twice a week and a dance oriented physical education class three times a week.
      The usual physical activity consisted mostly of playground activities. Students
      in the intervention had a significantly greater lowering in body mass index and
      resting heart rate than students in regular physical activity.

PMID- 7630999
TI  - The Intergenerational Life History Project: promoting health and reducing disease
      in adolescents and elders.
AB  - A 38-week Intergenerational Life History Project is designed to create a
      collaboration in a lower socioeconomic neighborhood between 50 elderly people in
      the community ages 80 and older (whose life reminiscences make them historians)
      and 50 high school seniors (who become scribes by writing down the elders' oral
      histories.) The youth-elder teams provide reciprocal social support and
      intergenerational mentorship through reminiscence. The project is an integrated,
      multifaceted effort to bring about health, behavior, and attitude changes in the
      two age cohorts challenged in different ways and for different reasons by
      morbidity and mortality.

PMID- 7631001
TI  - Steps in planning and developing health communication campaigns: a comment on
      CDC's framework for health communication.
AB  - This reviews the efforts of the Centers for Disease Control and Prevention to
      integrate effective health communication into its programs that are designed to
      change behaviors. Although the 10-step framework for developing and implementing
      the Centers' health communication programs is both practical and comprehensive,
      it is suggested that a reversal of steps 2 and 3 is a more logical sequence, is
      more consistent with the literature and, more importantly, could avoid
      misapplications of the framework by less experienced practitioners. Comment is
      also made on the dynamic nature of health communication planning and development,
      a point not made explicit in the Centers' framework.

PMID- 7631000
TI  - Pilot test of a cervical cancer prevention video developed for Alaska Native
      women.
AB  - Cancer of the cervix is twice as likely to occur among Alaska Native women than
      among Caucasian women in the United State. To understand some of the factors
      associated with this high incidence, a random sample of 528 Alaska Native women
      were surveyed about their knowledge, attitudes, and behavior regarding cervical
      cancer and its risk factors. From the results of the Alaska Native Women's Health
      Project study, the need for more public education related to cervical cancer
      prevention was identified. A review of existing educational resources revealed
      that no culturally appropriate materials related to cervical cancer had been
      developed for Alaska Native women. To increase Native women's knowledge about
      cervical cancer and to motivate them to obtain annual Papanicolaou tests, a 12
      minute videotape presentation was developed specifically for this population. The
      videotape portrayed Alaska Native women as role models from the community
      discussing cervical cancer and Papanicolaou tests and engaging in healthy
      lifestyles. The videotape was pilot tested with several groups of Alaska Native
      women. The women were surveyed before and after watching the video and were asked
      to rate the tape and make comments about it. The results of the posttest
      demonstrated a significant increase in the knowledge level of the participants.
      The videotape was well received because of its cultural sensitivity and
      appropriateness. On the basis of this study, the development of additional
      culturally appropriate educational materials related to cancer prevention of
      Alaska Native women is recommended.

PMID- 7631002
TI  - A gate to the city: the Baltimore Quarantine Station, 1918-28.

PMID- 7631003
TI  - $15 million study launched to improve HIV-AIDs care.

PMID- 7631004
TI  - NHSC issues notebooks on community primary care.

PMID- 7631005
TI  - Cancer predisposition, radiosensitivity and the risk of radiation-induced
      cancers. I. Background.
AB  - This paper presents an overview of current knowledge on genetic predisposition to
      cancer and on enhanced sensitivity of cancer-predisposed genotypes to cancers
      induced by ionizing radiation. It is intended to provide a background and set the
      stage for the next papers in this series in which we will assess how such
      heterogeneity (with respect to predisposition to cancer and presence of
      radiosensitivity genotypes) in a population may affect estimates of the risk of
      radiation-induced cancers. The main findings and/or conclusions of the present
      paper are the following: (1) "Cancer-predisposing genes" (i.e. those at which
      germinal mutations predispose to cancer) are present in the human genome; these
      genes are responsible not only for the rare familial cancer syndromes but also
      for a proportion of the common cancers. At least 21 such genes have now been
      cloned (including 9 tumor suppressor genes, 11 DNA repair genes and 1 proto
      oncogene); further, at least 8 putative tumor suppressor genes and a gene
      involved in ataxia telangiectasia have been localized to specific chromosomes.
      (2) These genes play crucial roles in the control of cellular proliferation,
      programmed cell death (apoptosis) and/or one or another DNA repair pathway.
      Consequently, mutations in these genes are likely to "liberate" the cells from
      the normal constraints imposed by them, resulting in unconstrained growth
      characteristic of cancer. (3) At present, the evidence for increased sensitivity
      of cancer-predisposed genotypes to radiation-induced cancers is limited. However,
      current knowledge of the known functions of the cancer-predisposing genes and of
      the consequences of mutations in these provide (a) sufficient grounds for
      assuming that the genotypes of those predisposed to cancer may be at an increased
      risk for radiation-induced cancers and (b) the rationale for attempts to estimate
      quantitatively the impact of genotype-dependent differences in cancer
      predisposition and radiosensitivity on cancer risks in an irradiated population.

PMID- 7631006
TI  - DNA strand breakage is correlated with unaltered base release after gamma
      irradiation.
AB  - Unaltered base release is correlated with strand breakage for gamma-irradiated
      bacteriophage PM2 DNA in aqueous solution at pH 7.4. The yield of DNA strand
      breaks is determined by the agarose gel electrophoresis method. High-performance
      liquid chromatography (HPLC) is used to assay the release of unaltered nucleic
      bases. Previously reported HPLC methods have been updated. Unaltered base release
      is linear with dose up to 424 Gy, where up to 0.2% of all DNA bases are released.
      No detectable amounts of unaltered nucleosides are released and, besides
      unaltered bases, only one other product released from DNA is observed. Base
      release yields do not reflect the PM2 GC content of 43%. Only 76% of all prompt
      strand breaks appear to be associated with the release of an unaltered free base,
      whereby the guanine, cytosine, adenine and thymine yields are 9, 27, 18 and 22%
      of the prompt strand break yield, respectively. Postirradiation incubation at 37
      degrees C for 24 h increases the strand break yield 1.38-fold and the unaltered
      base release yield 1.76-fold such that 97% of the final strand breaks appear to
      be associated with the release of an unaltered base, whereby the guanine,
      cytosine, adenine and thymine yields are 10, 36, 23 and 28% of the final strand
      break yield, respectively. These data indicate that, given proper conditions,
      nearly every strand break leads to a base release. The bearing of these results
      on OH radical attack leading to strand breakage and base release is discussed.

PMID- 7631007
TI  - The effect of defective DNA double-strand break repair on mutations and
      chromosome aberrations in the Chinese hamster cell mutant XR-V15B.
AB  - The radiosensitive Chinese hamster cell line XR-V15B was used to study the effect
      of decreased rejoining of DNA double-strand breaks (DSBs) on gene mutations and
      chromosome aberrations. XR-V15B cells are hypersensitive to the cytotoxic effects
      of neocarzinostatin (NCS) and methyl methanesulfonate (MMS). Both mutagens
      induced more chromosome aberrations in XR-V15B cells than in the parental cell
      strain. The clastogenic action of NCS was characterized by the induction of
      predominantly chromosome-type aberrations in cells of both strains, whereas MMS
      induced mainly chromatid aberrations. The frequency of induced gene mutations at
      the hprt locus was not increased compared to the parental V79 cells when
      considering the same survival level. Molecular analysis by multiplex polymerase
      chain reaction (PCR) of mutants induced by NCS revealed a high frequency of
      deletions in cells of both cell lines. Methyl methane-sulfonate induced mainly
      mutations without visible changes in the PCR pattern, which probably represent
      point mutations. Our findings suggest a link between a defect in DNA DSB repair
      and increased cytotoxic and clastogenic effects. However, a decreased ability to
      rejoin DNA DSBs does not seem to influence the incidence and types of gene
      mutations at the hprt locus induced by NCS and MMS.

PMID- 7631008
TI  - Modification of nucleolar protein B23 after exposure to ionizing radiation.
AB  - The responses of cells to ionizing radiation include induction and/or suppression
      of the expression of genes and proteins. In our investigations of alterations in
      cellular protein expression in response to ionizing radiation, we have used the
      techniques of two-dimensional polyacrylamide gel electrophoresis and silver
      staining. We compared the nuclear protein profiles of control and irradiated (6
      Gy, 4 h postirradiation) radioresistant squamous carcinoma cells (SQ-20B) and
      observed an alteration in the expression of a 40 kDa protein: control nuclei
      express a protein isoform with pI values between 5.4-5.8, while irradiated nuclei
      express a more acidic variant with pI values between 5.2-5.5. Using the cyanogen
      bromide/O-phthalaldehyde method followed by microsequencing analysis, we obtained
      an internal amino acid sequence and identified the 40 kDa protein as nucleolar
      protein B23. Western blotting experiments confirmed the internal amino acid
      sequencing results and showed both species (control, 5.4-5.8, irradiated, 5.2
      5.5) to be recognized by an anti-B23 monoclonal antibody. Radiolabeling of
      control and irradiated samples with [32P]NAD or [32P]orthophosphoric acid
      revealed the acidic species of B23 to be both ADP-ribosylated and phosphorylated.
      Therefore, exposure of SQ-20B cells to radiation results in the increase in
      expression of an ADP-ribosylated and phosphorylated species of B23.

PMID- 7631009
TI  - Insulin and insulin-like growth factor-1 (IGF-1) inhibit repair of potentially
      lethal radiation damage and chromosome aberrations and alter DNA repair kinetics
      in plateau-phase A549 cells.
AB  - Plateau-phase A549 cells exhibit a high capacity for repair of potentially lethal
      radiation damage (PLD) when allowed to recover in their own spent medium.
      Addition of either insulin or insulin-like growth factor-1 (IGF-1) to the spent
      medium 60 to 120 min before irradiation significantly inhibits PLD repair. The 9
      h recovery factor (survival with holding/survival without holding) is reduced
      from 10.8 +/- 0.7 to 3.4 +/- 0.3 by insulin and to 3.0 +/- 0.4 by IGF-1. Neither
      growth factor alters the cell age distribution of the plateau-phase cells,
      increases the rate of incorporation of 5-bromo-2'-deoxyuridine into DNA, or
      alters the extent of radiation-induced mitotic delay in cells subcultured
      immediately after irradiation. Both insulin and IGF-1 alter the kinetics for
      rejoining of DNA double-strand breaks (DSBs), slowing the fast component of
      rejoining significantly. However, these growth factors have no effect on the
      initial level of DSBs or on the percentage of residual unrejoined breaks at 120
      min postirradiation. Both growth factors affect repair of lesions leading to
      dicentric, but not to acentric, chromosome aberrations significantly. In control
      cells (treated with phosphate-buffered saline, 90 min prior to irradiation), the
      half-time for disappearance of dicentrics was 4.1 h (3.4 to 5.1 h), and 47.1 +/-
      3.7% of the residual damage remained at 24 h postirradiation. Insulin and IGF-1
      increased the half-time for disappearance of dicentrics to 5.2 h (3.9 to 7.7 h)
      and 5.7 h (5.5 to 5.9 h), respectively, and increased residual damage to 56.1 +/-
      5.9% and 60.8 +/- 6.0%, respectively. Overall, these data show that insulin and
      IGF-1 inhibit PLD repair in A549 cells by mechanisms which are independent of
      changes in cell cycle parameters. The data suggest that the growth factors act by
      inducing changes in chromatin conformation which promote misrepair of radiation
      damaged DNA.

PMID- 7631010
TI  - Comparison of gamma-ray-induced chromosome ring and inversion frequencies.
AB  - A method was used to detect chromosome inversions as apparent or false sister
      chromatid exchanges (SCEs) in the first mitosis after gamma irradiation of human
      G0 cells. Dose-response relationships for small inversions have not been measured
      and reported previously, but it has been assumed that these are induced with a
      frequency equal to that of their easily measured asymmetrical counterpart, the
      interstitial deletion. Our experiments confirm this expectation. The results also
      demonstrate, as others have suggested, that in protocols where SCEs have been
      reported in the first postirradiation mitosis after incorporation of BrdU in the
      previous cell cycle, the X- or gamma-ray treatment of G0- or G1-phase cells
      produces virtually no true SCEs.

PMID- 7631011
TI  - A critical analysis of the use of radiation inactivation to measure the mass of
      protein.
AB  - Measurements are presented of the radiation inactivation of four enzymes exposed
      to a 6 MeV proton beam. It has long been thought that the measurement of the
      susceptibility of an enzyme to ionizing radiation can be used to determine its
      molecular mass. Results are frequently interpreted using the empirical analysis
      of Kempner and Macey (Biochim. Biophys. Acta 163, 188-203, 1963). We examine this
      analysis and discuss the validity and limitations of the assumptions on which it
      is based. Our results indicate that the specific biochemical properties of each
      enzyme make a significant contribution to its radiation sensitivity.

PMID- 7631012
TI  - Effect of gallium-porphyrin analogue ATX-70 on nitroxide formation from a cyclic
      secondary amine by ultrasound: on the mechanism of sonodynamic activation.
AB  - Sonodynamic therapy is a promising new modality for cancer treatment based on the
      synergistic effect on tumor cell killing by combination of a drug (typically a
      photosensitizer) and ultrasound. The mechanism of sonodynamic action was
      suggested to involve photoexcitation of the sensitizer by sonoluminescent light,
      with subsequent formation of singlet oxygen. In this work we studied the aqueous
      sonochemical reactions of the gallium-porphyrin derivative ATX-70, one of the
      most active sonodynamic agents found, using 50 kHz ultrasound. The experiments
      were carried out in the presence of 2,2,6,6-tetramethyl-4-piperidone
      hydrochloride (TMP), which reacts with singlet oxygen or .OH radicals to give the
      EPR-detectable nitroxide 2,2,6,6-tetramethyl-4-piperidone-N-oxyl (TMP-NO).
      Recently it has been suggested that the enhancement of TMP-NO yields in the
      presence of aqueous solutions of ATX-70 exposed to ultrasound was evidence for
      the formation of singlet oxygen in the system. Our results show that the
      surfactant cetyltrimethylammonium bromide (CTAB) can mimic the ATX-70-induced
      increase in the TMP-NO signal, but it fails to reproduce the behavior of ATX-70
      in D2O: while the yields of TMP-NO in the presence of ATX-70 increase in D2O, the
      opposite effect was found with the surfactant CTAB. However, our data show that
      the increased TMP-NO yields in D2O are paralleled by an increased concentration
      of ATX-70 dimer, a form that is inactive in the photochemical generation of
      singlet oxygen. Our finding that the ATX-70-dependent enhancement of the TMP-NO
      signal was highest at approximately 20% O2, in both N2/O2 and argon/O2 mixtures,
      and decreased with increasing oxygen concentration is not compatible with the
      singlet oxygen mechanism. Finally, our results on the temperature dependence of
      the ATX-70-induced formation of TMP-NO are not consistent with the photochemical
      excitation of ATX-70 by sonoluminescent light: the ATX-70-dependent enhancement
      of TMP-NO signal increased with temperature in the range 10-25 degrees C, while
      the intensity of sonoluminescence of aqueous solutions both in multiple-bubble
      fields and in single-bubble experiments is known to decrease with increasing
      temperature.

PMID- 7631013
TI  - Thiazolidine prodrugs of cysteamine and cysteine as radioprotective agents.
AB  - The need for protection against the toxic effects of ionizing radiation comes
      from many different directions: occupational exposure, nuclear accidents,
      environmental sources and protection of normal tissue during the therapeutic
      irradiation of cancer. Sulfhydryl-containing compounds, including cysteamine and
      L-cysteine, have long been known to possess radioprotective properties, but their
      therapeutic utility is limited by their side effects at radioprotective doses. To
      avoid this drawback, thiazolidine prodrugs of cysteamine and L-cysteine were
      prepared by the condensation of each thioalmine with the aldose monosaccharides,
      D-ribose and D-glucose, producing RibCyst, GlcCyst, RibCys and GlcCys. The
      prodrugs were designed to liberate the parent thiolamine nonenzymatically, after
      ring opening and hydrolysis, which is then available to function as a
      radioprotective agent. Cysteamine's inherent toxicity, measured using Chinese
      hamster V79 cells growing in culture, was completely eliminated, even at
      concentrations as high as 25 mM, by providing the thiolamine in the form of a
      prodrug. Good protection against radiation-induced lethality was demonstrated by
      the cysteamine prodrugs using a clonogenic assay. Protection against radiation
      induced DNA single-strand breaks, as measured by alkaline elution, was also shown
      by both RibCyst and GlcCyst; this activity was higher than that exhibited by
      either cysteamine or WR-1065. The L-cysteine prodrugs, RibCys and GlcCys, also
      possessed radioprotective abilities under most of the conditions studied.
      Protection against DNA damage was comparable between L-cysteine, WR-1065 and
      RibCys.

PMID- 7631014
TI  - Subcellular and intranuclear localization of neptunium-237 (V) in rat liver.
AB  - The present investigation was aimed at establishing the distribution of 237Np
      within the different structures of hepatocytes. Rats were contaminated
      experimentally by intravenous injection of 237Np (V) and the subcellular
      structures of the liver were separated by ultracentrifugation. Twenty-four hours
      after contamination, the nuclear and cytosolic fractions bound 54 and 32%,
      respectively, of the total radionuclide. Purification of the nuclei followed by
      dissociation of the protein components in medium of increasing ionic strength
      showed a specific binding of neptunium to the structural proteins of the nuclear
      matrix.

PMID- 7631016
TI  - Postoperative irradiation impairs or enhances wound strength depending on time of
      administration.
AB  - Irradiation can complicate surgical wound healing, yet little is known of the
      importance of the time between surgery and irradiation on this process. This
      study investigated the impact of postoperative irradiation on gain in would
      tensile strength in a murine skin model. Irradiation on the same day as wounding
      or to 2-day-old wounds reduced wound tensile strength. In contrast, postoperative
      irradiation delivered at 7, 9 and 14 days transiently enhanced wound tensile
      strength, as measured 3 but not 4 or 5 weeks later. This effect was independent
      of the inclusion (hemibody) or exclusion (skin alone) of the hematopoietic system
      in the field of irradiation. Radiation-enhanced wound tensile strength was
      greater and occurred earlier after higher radiation doses. Even though the effect
      of irradiation in enhancing wound tensile strength is transitory, it could be
      important in assisting early wound healing.

PMID- 7631015
TI  - Radioresistant DNA synthesis in SV40-immortalized ataxia telangiectasia
      fibroblasts.
AB  - Ataxia telangiectasia (AT) is an autosomal recessive disease, characterized by
      both neurological disorders and a high incidence of early-onset cancers. On a
      cellular level, cellular radiosensitivity and radioresistant DNA synthesis are
      the hallmarks of AT. While expression of cellular radiosensitivity varies
      somewhat among affected individuals, radioresistant DNA synthesis is seen
      consistently and, in fact, is the only end point used for assigning individuals
      to genetic complementation groups. For this reason, complementation-group
      specific correction of radioresistant DNA synthesis in AT cells has long been
      thought to be an absolute requirement for confirmation of a bona fide clone of an
      AT gene. Since primary AT cells grow poorly in culture, SV40-immortalized AT
      fibroblasts are the usual recipients of transfected DNA in these studies. In
      experiments reported here, we demonstrate that SV40-immortalized AT fibroblasts
      have significantly reduced radioresistant DNA synthesis compared to primary AT
      fibroblasts, and their response to radiation is more like normal cells, in that
      both the radiosensitive and radioresistant components appear to be present. This
      suggests that there may be an interaction between SV40 proteins and the AT gene
      product or its downstream elements. This partial "complementation" of
      radioresistant DNA synthesis in SV40-immortalized AT cells complicates
      complementation cloning strategies, and should be considered when terminally
      screening putative AT gene clones by analysis of radioresistant DNA synthesis.

PMID- 7631017
TI  - Proliferation-independent growth factor modulation of the radiation sensitivity
      of human prostate cells.
AB  - The survival of human prostatic epithelial cells irradiated in different
      physiological states is reported. Exponentially growing cells and contact
      inhibited cells grown and irradiated in the presence of the growth factors
      epidermal growth factor (EGF) and bovine pituitary extract (bPE) had overlapping
      radiation dose-cell survival curves. However, when EGF and bPE were removed from
      exponentially growing cells before irradiation, an increase in radiosensitivity
      was observed if the cells were replated into medium containing growth factors
      (EGF and bPE) immediately after irradiation. Treating cells with the nonspecific
      growth factor receptor antagonist suramin had similar effects as did growth
      factor deprivation. In contrast, when growth factor-deprived cells were
      maintained in this same medium for 12 h postirradiation, an increase in radiation
      survival was observed. This increase in survival is attributed to the repair of
      potentially lethal damage (PLD). Both the increase in radiosensitivity induced by
      deprivation of growth factor before irradiation and the repair of PLD caused by
      deprivation of growth factor after irradiation were independent of changes in
      cellular proliferation.

PMID- 7631018
TI  - Exercise intolerance in patients with chronic heart failure.
AB  - Patients with chronic heart failure (CHF) experience significant morbidity
      because of dyspnea and fatigue with activities of daily living. Although central
      hemodynamic abnormalities are the hallmark of this disorder, investigators have
      not shown a relationship between left ventricular ejection fraction or exercise
      pulmonary capillary wedge pressure and exercise intolerance in this disorder.
      Recent studies have focused on the contributions of pulmonary abnormalities and
      alterations in peripheral vasomotor control and skeletal muscle in exercise
      intolerance in this disorder. Early anaerobic metabolism occurs in patients with
      CHF and appears to be caused by a combination of reduced skeletal muscle blood
      flow and decreased aerobic enzyme content in skeletal muscle. Atrophy in skeletal
      muscle and alterations in skeletal muscle fiber typing are accompanied by
      alterations in contractile function in skeletal muscle. These results suggest
      that exercise intolerance in patients with CHF is multifactorial, and that
      research efforts must consider central hemodynamic abnormalities, pulmonary
      abnormalities, and alterations in peripheral blood flow and skeletal muscle
      biochemistry and histology. The present review will explore current research in
      this area and develop a model for understanding exercise intolerance in CHF.

PMID- 7631020
TI  - Metabolic control of the circulation: implications for congestive heart failure.
AB  - The role of metabolic processes in the control of the normal circulation will be
      discussed with particular emphasis on how metabolic events, particularly those
      that occur with the performance of exercise, result in production of vasoactive
      substances and sympathetic activation. Heart failure patients will have altered
      metabolism, particularly in skeletal muscle, that may result in a lesser degree
      of peripheral vasodilation and will also have an abnormal response to sympathetic
      stimuli, with less cardiac stimulation but preserved peripheral vasoconstriction.
      The consequences of these abnormalities on the hemodynamics and metabolic
      processes that occur with exercise in the heart failure patient will be discussed
      in detail. The effect of therapeutic interventions such as drug therapy and
      exercise training will be reviewed.

PMID- 7631019
TI  - The role of endothelium-derived vasoactive substances in the pathophysiology of
      exercise intolerance in patients with congestive heart failure.
AB  - The vascular endothelium releases vasoactive substances that appear to play an
      important role in the normal regulation of peripheral vasomotor tone. Nitric
      oxide, endothelins, prostaglandins, and other endothelium-derived vasodilating
      and vasoconstricting factors are released by the vascular endothelium in response
      to a diverse array of hormonal, pharmacologic, chemical, and physical stimuli.
      Shear stress, produced by pulsatile blood flow at the endothelial cell luminal
      surface, alters endothelial production of several endothelium-derived vasoactive
      substances, which may contribute to regional regulation of skeletal muscle blood
      flow during exercise. Abnormal vascular endothelium function has been shown in
      both experimental and clinical heart failure. Preliminary data suggest that
      abnormalities of endothelial function may contribute to increased peripheral
      vasomotor tone during exercise in patients with congestive heart failure.

PMID- 7631022
TI  - 38 hour week--your questions answered.

PMID- 7631021
TI  - Antithrombotic and thrombolytic therapy in patients undergoing coronary artery
      interventions: a review.
AB  - The controlled arterial injury that occurs with balloon angioplasty and other
      coronary interventions is characterized by evanescent endothelial denudation and
      vascular disruption. As a consequence, platelet activation occurs at the treated
      site, and there is a risk of thrombotic occlusion. This risk is heightened by
      several factors including unstable clinical presentation, lesion complexity, deep
      injury, and dissection. Aspirin has been shown to unquestionably reduce, although
      not eliminate, acute complications and is now part of the routine periprocedural
      regimen. Heparinization with more intense anticoagulation than is conventionally
      used is also standard treatment and is initiated before vessel instrumentation.
      Adjunctive thrombolysis is rarely necessary unless refractory thrombus precedes
      or complicates the procedure. However, thrombolysis may have a role in the
      treatment of saphenous vein graft obstructive lesions in which guide wire- or
      catheter-induced distal thromboembolization may cause infarction in spite of
      successful graft recanalization. In contrast to their success in the
      periprocedural phase of coronary interventions, anticoagulants and a wide variety
      of platelet active agents have been ineffective in reducing the 30% to 40%
      incidence of restenosis. Only 7E3, which targets the final common pathway of
      platelet aggregation by irreversibly blocking the IIb/IIIa receptor, has been
      shown to decrease the 6-month clinical event rate after balloon angioplasty,
      possibly by a surface pacification mechanism. This suggests that newer more
      potent antiplatelet and anticoagulant agents may also find a role in the long
      term management of these patients.

PMID- 7631023
TI  - Does the interval between fractions matter in the range of 4-8 h in radiotherapy?
      A study of acute and late human skin reactions.
AB  - Accelerated radiotherapy has the potential to increase local control of rapidly
      growing tumours. To determine the necessary time interval for complete repair of
      sublethal damage in normal tissue in a clinical situation, we have compared the
      acute and late skin reactions with 8 and 24 h between fractions, using the same
      dose per fraction and total dose. Forty-nine breast cancer patients participated
      in this study, and received bilateral parasternal irradiation to 50 Gy with 2 Gy
      per fraction as part of their adjuvant postoperative radiotherapy. The time
      interval between daily fractions was always 8 h on the left field and 24 h on the
      right, and the total treatment time was 2.5 and 5 weeks, respectively. The acute
      endpoint was erythema, measured by reflectance spectrophotometry and an acute
      reaction score for erythema and desquamation. The late endpoint was
      telangiectasia, scored on an arbitrary scale. The results have also been compared
      with those in a previously treated group of patients with 4 and 24 h between
      fractions. The degree of acute reactions was decreased with an 8-h interval
      compared with 24 h between fractions with the peak acute score as endpoint; no
      difference was seen with the peak reflectance measurements. The maximal
      expression occurs approximately 1 week earlier with the accelerated schedule,
      possibly as a consequence of the reduction of the treatment time. The pattern of
      the acute reaction for 8 h between fractions is similar to that for 4 h.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7631025
TI  - Epidermoid carcinoma of the anal margin: 17 cases treated with curative-intent
      radiation therapy.
AB  - Between 1973 and 1991, 17 patients with epidermoid carcinoma of the anal margin
      without evidence of distant metastasis were treated with curative-intent
      radiation therapy (RT). There were nine T1-tumors, six T2-, one T3- and one T4
      tumor; two patients presented with inguinal node involvement: one N1 and one N3.
      Nine patients underwent prior incomplete local excision (six with microscopic
      involvement of surgical margins and two with macroscopic residual disease). The
      radiation dose to the tumor was 60-70 Gy; the radiation dose to the inguinal
      lymph nodes was 40-45 Gy in N0, and 50-60 Gy for involved inguinal nodes. The 5-
      and 10-year cancer-specific survival rates were 86.2% and 77.5%, respectively.
      The same probabilities were 100% and 100% for T1-tumors, 60% and 40% for T2
      tumors. Severe complications occurred in two patients, one anal radionecrosis
      requiring a colostomy and one permanent anal incontinence after local excision,
      which was non-related to irradiation. For the cured patients, the sphincter
      preservation rate after 5 years was 82% (9/11). In univariate analysis and in Cox
      multivariate analysis, the cancer-specific survival rate was influenced by one
      factor: the tumor size.

PMID- 7631024
TI  - Irradiation of bone metastases in breast cancer patients: a randomized study with
      1 year follow-up.
AB  - The results from a prospective randomized trial comparing two different radiation
      schedules for treatment of painful bone metastases in women with recurrent breast
      cancer are presented. A total of 217 patients with painful bone metastases were
      randomized to either 30 Grey (Gy) in ten fractions, five fractions a week (5F/W)
      or 15 Gy in three fractions 2F/W. The effect of treatment was evaluated by pain
      assessment, the radiological response and the degree of side-effects. The
      patients were rated at start of treatment and after 1, 3, 6 and 12 months. No
      difference between the two radiation regimes was found, neither in achieved pain
      relief, improvement in level of activity and medication, nor was there any
      difference in radiological response and side-effects from treatment. Both regimes
      resulted in a significant improvement in both pain score and level of activity 1
      month after treatment, an improvement which persisted during the follow-up
      period. We conclude that 15 Gy given in three fractions 2F/W is as effective as
      30 Gy in ten fractions 5F/W, but more convenient to the patient and of less cost
      to society.

PMID- 7631026
TI  - Renal damage after total body irradiation in a mouse model for bone marrow
      transplantation: effect of radiation dose rate.
AB  - Late renal damage after total body irradiation (TBI) and bone marrow
      transplantation (BMT) is a recently recognised morbidity. We have tested the
      effect of single fraction TBI given at two different dose rates on late kidney
      damage in a mouse model. TBI was given at either high dose rate (HDR; 0.71
      Gy/min) or low dose rate (LDR; 0.08 Gy/min). Transplantation with syngeneic
      marrow cells was done 4-6 h after TBI. Kidney damage was tested using 51CrEDTA
      residual activity, blood urea nitrogen (BUN) and percentage haematocrit (Hct).
      TBI alone given at HDR or LDR caused progressive renal damage with no evidence of
      recovery or plateau. The time latency before the expression of damage was
      dependent on both dose and the end point used. It was shorter the higher the
      dose. 51CrEDTA detected renal damage at the same doses as BUN but earlier in
      time, while %Hct showed evidence of renal damage at doses lower than both BUN and
      51CrEDTA. Using the 51CrEDTA the dose-response curves for renal damage were steep
      and continuously shifting towards lower doses as follow-up time after treatment
      increased. There was a sparing effect of reducing the dose rate that was more
      evident at follow-up times of less than a year than at 66 weeks after TBI. Thus,
      the dose modifying ratio (DMF), defined as the dose needed to cause renal damage
      in 50% of irradiated animals (ED50) using LDR divided by the ED50 using HDR, was
      dependent on the time of evaluation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7631027
TI  - Correlation of breast dose heterogeneity with breast size using 3D CT planning
      and dose-volume histograms.
AB  - The aim of this study was to evaluate the effect of breast size on dose
      heterogeneity. Twenty women underwent a planning CT scan of the thorax. A three
      dimensional treatment plan was devised for each patient using a standard
      technique of isocentric medial and lateral wedged tangential fields. Three
      dimensional dose distributions were derived using an equivalent path length (EPL)
      inhomogeneity correction and cumulative dose-volume histogram (DVH) data
      calculated for the breast. Analysis of the DVHs for each patient reveals that 0.2
      23.8% of the breast received an absorbed dose outside the desired 95-105% of that
      prescribed at the isocentre. The degree of dose heterogeneity was most strongly
      correlated with breast volume (r = 0.70, 95% confidence interval (C.I.) 0.37
      0.87). There was also a positive correlation for breast dose heterogeneity versus
      brassiere (bra) cup size (Spearman rank correlation rho = 0.62), breast area (r =
      0.39, 95% C.I. -0.06-0.71) and chest wall separation (r = 0.31, 95% C.I. -0.15
      0.66). We conclude that breast size is an important determinant of dose
      heterogeneity within the breast.

PMID- 7631028
TI  - Depth dose under narrow shielding blocks: a comparison of measured and calculated
      dose.
AB  - This paper describes measurements done to investigate the accuracy of dose
      calculation algorithms when used to calculate the dose under shielding blocks.
      Because the prescribed dose is sometimes limited by the dose to organs at risk
      within the irradiated volume, it is important to know the dose under a block
      accurately. Five different algorithms from four treatment planning systems were
      used to calculate the dose under two narrow lead alloy blocks each placed
      centrally in a 15 x 15-cm beam of 6- and 18-MV X-rays, respectively. Measurements
      were done in a water phantom with the same geometrical set-up. All measured data
      have a common feature; a high surface dose (up to about 20%) decreasing linearly
      within the first 1-2 cm to a minimum ranging from 13 to 6.5%, and then increasing
      to a maximum depending on the X-ray energy and block width. Beyond the maximum,
      the dose decreases approximately linearly due to absorption of the primary beam.
      The first part of the curve is due essentially to secondary electrons. Beyond the
      minimum, the X-ray scatter dose component increases, due to increasing phantom
      scatter, to a maximum which is greater for 6 MV than for 18 MV X-rays. Most
      algorithms could not reproduce measured data accurately.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7631029
TI  - The explanation for the influence of prescription habits on radiation dose-time
      parameters for head and neck tumour control.

PMID- 7631030
TI  - The inconclusive role of treatment time in radiotherapy of head and neck tumours.

PMID- 7631031
TI  - Why should rheumatologists collect patient self-report questionnaires in routine
      rheumatologic care?
AB  - In this article, a rationale for routine use of self-report questionnaires in
      rheumatology clinical care is presented. Studies performed according to
      structured clinical research methodologies, including population-based studies,
      inception cohort studies, randomized controlled clinical trials, and meta
      analyses of these trials, have significant limitations in describing accurately
      the long-term natural history and results of treatment of rheumatoid arthritis;
      the most accurate data have been derived from clinical observations of
      consecutive, nonselected patients in routine clinical settings. Self-report
      questionnaires provide accurate and representative data concerning clinical
      status and traditional laboratory and variables in large numbers of patients can
      be developed using microcomputer hardware and software available only over the
      last decade. Further collection of self-report data in rheumatology clinical care
      should result in more informative descriptions of the long-term natural history
      and results of therapy in rheumatoid arthritis.

PMID- 7631032
TI  - Data collection in the clinic.
AB  - Important contributions to the understanding of rheumatic diseases can be made by
      clinicians in university and nonuniversity settings performing research as part
      of ordinary patient-care activities. This article describes in detail cost
      effective methodologies that have been used to develop successful, longitudinal
      research and clinical care databanks. Specific forms and detailed recommendations
      are also included.

PMID- 7631033
TI  - Systems for data analysis.
AB  - A system for data analysis is the end product of study planning, form design,
      data entry, data verification, and statistical analysis. This article reviews
      these steps and considers the fundamental choices in software for data entry and
      analysis. The appendix includes a listing of general and specialized software for
      data management and statistical analysis.

PMID- 7631034
TI  - Radiographic indices for osteoarthritis.
AB  - There are now validated radiographic indices that can be used by clinical
      investigators to determine the prevalence and severity of OA of the hand, hip,
      knee, apophyseal joints of the cervical and lumbar spine, and cervical disc
      degeneration. Clinical investigators should consult standardized atlases for
      radiographic index descriptions. The use of an atlas and training sessions
      improve the agreement between and within readers. The standard global grades
      developed by Kellgren and Lawrence have been used in epidemiologic studies to
      determine the prevalence of OA in specific joints. The evaluation of radiographic
      OA by individual radiographic features allows for the characterization of the
      variation in radiographic features often found in OA and in degenerative disc
      disease. Methods have been developed to maintain interrater and intrarater
      agreement in scoring radiographs. Radiographic indices of OA can now be reliably
      applied to clinical epidemiologic-based studies of OA.

PMID- 7631035
TI  - Radiographic assessment of rheumatoid arthritis.
AB  - In this article, the rationale for the use of radiographs in the assessment of
      patients with rheumatoid arthritis is presented, along with a discussion of the
      choice of radiographs to be used. The author's choices for the scoring methods
      best used for minimal, intermediate, and more comprehensive databases for use in
      clinical research, other available scoring methods, factors influencing the type
      of database to be employed, and prior applications of scoring methods are also
      discussed.

PMID- 7631036
TI  - Laboratory tests.
AB  - Despite impressive advances in our understanding of the natural history of the
      rheumatic diseases and their treatments, there remains much to be learned. The
      management of most of these diseases is far from satisfactory for either the
      clinician or patient. There is little distinction between clinical practice and
      clinical research. How much and what type of data one should collect clearly
      depends on the setting and on the clinical/research questions being asked. One
      must ensure that the literature is relevant to his or her practice. The corollary
      is that research must be derived from a variety of settings, including both the
      traditional researcher and the traditional clinician.

PMID- 7631037
TI  - Joint counts and physical measures.
AB  - The joint examination is the major source of information to determine clinical
      status of rheumatoid arthritis in the clinic or in a clinical trial. Quantitative
      methods may evaluate tenderness, pain on motion, swelling, deformity, and
      limitation of motion. Use of self-report, simplified, reduced, and binary
      (normal/abnormal) evaluations are presented in this article with emphasis on
      using binary evaluations in clinical settings. The uses of grip strength, button
      test, and walk time are also discussed.

PMID- 7631038
TI  - Health status questionnaires.
AB  - Because they accurately and efficiently tap into important aspects of rheumatic
      disease status and outcome, health status questionnaires have found increasing
      use in the clinic, controlled clinical trials, and observational studies. This
      article reviews utility assessment methodologies as well as generic and disease
      specific health status questionnaires relevant to rheumatology.

PMID- 7631039
TI  - Psychologic assessment in rheumatology.
AB  - In rheumatology practice and applied research, there are numerous psychologic
      issues that merit special attention, including depression, helplessness, self
      efficacy, and coping. A wide variety of measures are available for addressing
      these issues. The tests themselves must meet the psychometric criteria of
      reliability and validity. Psychologic tests must be administered under
      standardized conditions.

PMID- 7631040
TI  - A database for rheumatoid arthritis.
AB  - This article describes a methodology for the establishment and maintenance of a
      longitudinal rheumatoid arthritis database, addresses concerns regarding validity
      and reliability of longitudinal data collection in the setting of clinical care
      and research, and describes and recommends specific variables for minimal,
      moderate, and extensive levels of database detail.

PMID- 7631041
TI  - A database for systemic lupus erythematosus and systemic connective tissue
      disorders.
AB  - Connective tissue diseases (CTDs) typically have a wide spectrum of symptoms that
      vary widely over time, often requiring a large array of medications and
      laboratory tests. This presents a challenge in all stages of database
      development, including the selection of data elements, collection methods, coding
      of variables, and selection of a relational database with the potential for
      tracking. There is a distinct need for valid, reliable data in a usable form to
      assist in the diagnosis, management, and research of CTDs. This article discusses
      the factors involved, provides examples of data collection tools that are
      presently used, and suggests how they might be employed by the physician in
      diagnosis and management of CTDs.

PMID- 7631042
TI  - A database for fibromyalgia.
AB  - FMS is a complex condition mainly characterized by the presence of chronic pain.
      The nature of this complaint thus demands assessment in a hierarchal fashion of
      the various components of the pain system ranging from the nociceptor through to
      complex central pain-processing mechanisms. The condition is common and
      represents the most important defined chronic pain syndrome. Elucidation of the
      mechanisms and better management of FMS will result in improved knowledge of a
      whole range of related chronic pain syndromes. The database in FMS is necessarily
      large but does need to be focused according to the need of the person
      constructing the database and the need of the individual with FMS. As our
      understanding of FMS evolves, better ways of assessing the various dimensions of
      the problem will be devised. Perhaps the challenge we face is to bring all the
      parts together. In doing so, we may find there is a single essential component
      that links all the clinical features together, which correlates well with
      severity, disability and outcome, which is amenable to treatment programs, and
      which is measurable. The search for the soul of the "elephant" of FMS continues.

PMID- 7631044
TI  - Why health care reform was and still is impossible.

PMID- 7631043
TI  - A database for back (axial skeletal) pain.
AB  - Back pain cannot be considered a mere symptom that has as its only function
      reference to relevant hidden disease. Back pain must be acknowledged as a
      disorder that requires description and assessment as carefully as any of the well
      established clinical entities. This article outlines a clinically useful,
      descriptive "morphology" or nosography of the various axial skeletal pains
      stated, and proposes methods for their classification and evaluation.

PMID- 7631045
TI  - Biochemistry of prostaglandin endoperoxide H synthase-1 and synthase-2 and their
      differential susceptibility to nonsteroidal anti-inflammatory drugs.
AB  - The principal pharmacological effects of nonsteroidal anti-inflammatory drugs
      (NSAIDs) are due to their ability to inhibit prostaglandin synthesis. NSAIDs
      block the cyclooxygenase activities of the closely related PGH synthase-1 and PGH
      synthase-2 (PGHS-1 and PGHS-2) isozymes. NSAIDs are therapeutically useful due to
      their analgesic, anti-pyretic, anti-inflammatory, and anti-thrombogenic
      properties. Major side-effects of NSAIDs include their ulcerogenic and
      nephrotoxic activities. All clinically approved NSAIDs in general use today
      inhibit both PGHS-1 and PGHS-2. Recently, inhibitors have been identified that
      are selective toward PGHS-2 and that have potent analgesic and anti-inflammatory
      activities with minimal ulcerogenic activity. If the new PGHS-2 selective NSAIDs
      can effectively inhibit inflammatory prostaglandin synthesis by PGHS-2, without
      inhibiting PGHS-1 prostaglandin synthesis required to regulate sodium and water
      resorption, and renal blood flow, it is likely that these new drugs will also
      have significantly less renal toxicity than present-day NSAIDs. In this article,
      the mechanisms of actions of NSAIDs primarily at the biochemical level, including
      the reactions catalyzed by PGHSs, will be discussed. In addition, the biochemical
      properties of these isozymes, and the differential regulation of the PGHS-1 and
      PGHS-2 genes, will be examined.

PMID- 7631046
TI  - Interactions of the vasoconstrictor peptides, angiotensin II and endothelin-1,
      with vasodilatory prostaglandins.
AB  - Vasoconstrictor peptides, such as angiotensin II (Ang II) and endothelin-1 (ET
      1), stimulate the synthesis and release of vasodilatory prostaglandins from
      multiple tissues and diverse cellular types. The synthesis of PGE2 and PGI2 acts
      as a negative feedback loop to antagonize the contractile actions of Ang II and
      ET-1. Inhibition of prostaglandin synthesis with nonsteroidal anti-inflammatory
      drugs (NSAIDs) enhances the constrictor actions of Ang II and ET-1 on the
      vasculature of the kidney and on the glomerulus. The enhanced production of
      prostaglandins, in response to constrictor peptides, is both short- and long
      term. Prostaglandin synthesis is regulated at multiple steps, including: (1)
      phospholipase A2, which releases arachidonic acid from membrane phospholipids;
      (2) PGH synthase (PGHS), which converts arachidonic acid to the endoperoxides
      PGG2 and PGH2; and (3) PG synthases convert the endoperoxides to PGI2, PGE2, and
      others. ET-1 acutely activates phospholipase A2 through phosphorylation and acute
      increases of intracellular calcium. ET-1 also chronically enhances phospholipase
      A2 activity by transcriptional induction of this enzyme. There are no known acute
      effects of ET-1 to acutely enhance PGHS activity through posttranslational
      modification of the molecule. Chronically, however, cellular content of PGHS-2
      can be induced through transcriptional induction of the enzyme in response to ET
      1. Hence, ET-1 short- and long-term activates a modulatory feedback pathway that
      depends on upregulation of arachidonic acid release through phospholipase A2 and
      enhanced synthesis of prostaglandin endoperoxides through PGHS-2.

PMID- 7631047
TI  - The effects of nonsteroidal anti-inflammatory drugs on renal function:
      experimental studies in animals.
AB  - Studies in various experimental animal models have been invaluable in delineating
      the physiological and pathophysiological conditions under which renal
      prostaglandin (PG) synthesis is a major determinant of renal function; conditions
      in which the inhibition of renal PG synthesis by the administration of a
      nonsteroidal anti-inflammatory drug (NSAID) will significantly alter kidney
      function. This article presents the initial schema or concept that under certain
      well-defined conditions or disease states, an increase in renal sympathetic
      adrenergic and/or angiotensin II activity stimulates an increase in the synthesis
      of vasodilatory PG (PGE2/PGI2) to offset or modulate the vasoconstriction. In
      these renal "PG-dependent" states, a reduction of renal PG by NSAID
      administration adversely affects renal function by causing renal
      vasoconstriction, thus decreasing glomerular filtration and causing the retention
      of sodium and water. More recent experimental data from animal models are then
      reviewed to illustrate that the number of conditions or disease states in which
      renal function is PG-dependent has increased dramatically. Last, evidence is
      reviewed suggesting that under certain conditions, inherent increases in the
      synthesis of renal vasodilatory PGE2 and PGI2 and/or vasoconstrictive thromboxane
      A2 (TxA2) may be occurring. In these situations, renal function would also be
      more susceptible to NSAID-induced renal vasoconstriction and sodium retention.

PMID- 7631048
TI  - Clinical acute renal failure with nonsteroidal anti-inflammatory drugs.
AB  - Under baseline euvolemic conditions, prostaglandins play little to no role in the
      minute-to-minute regulation of renal function. Where these compounds come to
      serve a major role is in the setting of a systemic or intrarenal circulatory
      disturbance. In the setting of a decreased absolute or effective circulatory
      volume, a number of vasoconstrictor effectors are stimulated whose function is to
      preserve the systemic circulation. At the same time, these compounds stimulate
      the synthesis of renal vasodilatory prostaglandins. In turn, prostaglandins
      oppose the vasoconstrictive effect of these effectors such that the renal
      circulation remains well-preserved while the rest of the circulation is clamped
      down. Predictably, inhibition of prostaglandin synthesis would lead to unopposed
      renal vasoconstriction, resulting in a precipitous decline in renal function.
      Clinical conditions in which the renal circulation is critically dependent on the
      effect of vasodilatory prostaglandins include volume depletion, congestive heart
      failure, and cirrhosis. There are other conditions in which the circulatory
      volume is normal, but due to the intrarenal generation of vasoconstrictors, the
      kidney is similarly dependent on vasodilatory prostaglandins. Such conditions
      include glomerulonephritis and urinary tract obstruction.

PMID- 7631049
TI  - Interstitial nephritis, the nephrotic syndrome, and chronic renal failure
      secondary to nonsteroidal anti-inflammatory drugs.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) may induce a variety of acute and
      chronic renal lesions. Acute interstitial nephritis can follow the use of nearly
      all NSAIDs, but the number of reported cases is low. Most of these patients are
      elderly and develop a nephrotic syndrome with acute renal failure while taking
      NSAID for months. Renal biopsy shows acute tubulo-interstitial lesions with
      minimal changes in the glomeruli. The renal signs usually improve after
      discontinuing the drug, with or without steroid therapy, but chronic renal
      insufficiency or even end-stage renal disease (ESRD) are possible hazards. There
      is evidence that interstitial nephritis results mainly from a delayed
      hypersensitivity response to NSAID, and nephrotic syndrome results from changes
      in glomerular permeability mediated by prostaglandins and other hormones.
      Nephrotic syndrome without interstitial nephritis may occur, as well as immune
      complex glomerulopathy, in a small subset of patients receiving NSAIDs. Patients
      taking NSAID for months or years may develop papillary necrosis, chronic
      interstitial nephritis, or even ESRD. Case-control studies suggest that patients
      at risk are older men who suffer from chronic heart disease and renal
      hypoperfusion. Impaired medullary circulation and direct toxicity due to a drug
      metabolite seem to play a critical role in inducing interstitial fibrosis, which
      can be facilitated by a sustained production of some growth factors and
      cytokines.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7631051
TI  - The effects of nonsteroidal anti-inflammatory drugs on human hypertensive
      vascular disease.
AB  - The co-administration of nonsteroidal anti-inflammatory drugs (NSAIDs) and
      antihypertensive agents often, but not always, results in blunting of the effect
      of antihypertensive therapy. Although NSAIDs have no detectable pressor effects
      in normal subjects or untreated hypertensive people, they seem to antagonize the
      action of the majority of antihypertensive agents, making it necessary to
      increase their dosage, and often preventing proper control of blood pressure,
      particularly in black and elderly patients. The mechanism of this pharmacodynamic
      interaction is not completely understood, but may involve inhibition of vascular
      and renal prostaglandin (PG) synthesis, with resulting vasoconstriction and
      impaired renal excretion of Na+ and water. Also, suppression of a possible
      intermediary action of PG in the antihypertensive action of agents such as
      angiotensin converting enzyme inhibitors has been proposed. Certain
      antihypertensive drugs, such as Ca(2+)-channel blockers, centrally acting alpha
      agonists, and diuretics seem less sensitive to antagonism by NSAIDs. Aspirin and
      sulindac seem to be devoid of pressor effects, and thus provide a safe
      alternative in patients at risk for this interaction. These compounds may, in
      selected circumstances, even potentiate the effects of antihypertensive
      medications. Studies are underway to evaluate the hemodynamic effects of more
      selective blockers of arachidonate metabolism, such as thromboxane synthase
      inhibitors and selective inhibitors of PGH synthase-2.

PMID- 7631050
TI  - The effects of nonsteroidal anti-inflammatory drugs on glomerular filtration of
      proteins and their therapeutic utility.
AB  - Cyclooxygenase inhibitors have long been used in experimental studies as well as
      in clinical practice to reduce urinary protein excretion in proteinuric renal
      diseases. However, the mechanisms by which this treatment limits glomerular
      filtration of proteins are not fully elucidated. We will review the cellular and
      molecular mechanisms that regulate glomerular permselectivity and the
      experimental observations available on the effect of nonsteroidal anti
      inflammatory drugs (NSAIDs) on these glomerular functions. The effects of NSAIDs
      on glomerular microcirculation will also be analyzed in comparison with another
      class of drugs used to lower proteinuria in nephrotic patients, the angiotensin
      converting enzyme inhibitors. Finally, we will analyze the relationship between
      urinary prostaglandins and thromboxane A2 and discuss the effects of modulating
      these hormones on glomerular functions.

PMID- 7631052
TI  - Proceedings of the XIth meeting of the World Society for Stereotactic and
      Functional Neurosurgery. Part 1. Ixtapa, Mexico, October 11-15, 1993. Dedicated
      to Professor Edward R. Hitchcock.

PMID- 7631053
TI  - Increase of cerebral blood flow and improvement of brain motor control following
      spinal cord stimulation in ischemic spastic hemiparesis.
AB  - A 64-year-old man had an ischemic stroke in the left parietotemporal cortical
      subcortical areas. He developed a severe right spastic hemiparesis and dysphasia.
      An angiographic study showed left internal carotid artery occlusion and right
      internal carotid artery stenosis. A right internal endoarteriectomy was performed
      without any clinical improvement. After 1 year the patient was a candidate for
      cervical spinal cord stimulation (SCS) for the treatment of his spastic
      hemiparesis. An epidural electrode (Medtronic Sigma 3483) was positioned at the
      cervical level, mediodorsal to the cord. Clinical and neurophysiological studies
      (surface polyelectromyography, PEMG, for evaluation of brain motor control) were
      performed before and after 7 days of SCS (0.2 ms, 80 c/s, intensity for
      paresthesiae, continuous mode). A transcranial Doppler (TCD) study of both middle
      cerebral arteries (MCA) at rest and during SCS was performed on two occasions.
      SCS was followed by improvement of voluntary movement, decrease of spasticity and
      better endurance. The clinical findings were confirmed by the PEMG recordings.
      TCD examination showed an increase of flow velocities on both the right MCA
      (+43%) and the left MCA (+130%) during SCS. Such a TCD pattern, suggesting an
      increase of cerebral blood flow (CBF) during SCS, was reproducible. This case
      confirms efficacy of SCS in the treatment of ischemic hemiparesis and the
      increase of CBF following cervical SCS in man. The marked increase of CBF,
      particularly evident on the ischemic side, may play a role in mediating the
      improvement of motor control in our patient together with a possible arousal of
      the so-called 'sleeping neurons' of the penumbra zone.

PMID- 7631054
TI  - Management of intractable spasticity of supraspinal origin by chronic cervical
      intrathecal infusion of baclofen.
AB  - Today it is accepted that chronic infusion of baclofen produces significant
      relaxation and drastic reduction of spasms, amelioration of cramping pain and
      improvement of sphincter functions in spasticity of spinal cord origin. Based on
      these results our group had the opportunity of treating 11 cases with refractory
      spasticity and dystonic symptoms due to central damage caused by head injury in 8
      cases and to cerebral palsy in 3 using cervical intrathecal infusion of baclofen.
      During the trial period with percutaneous intrathecal infusion of a daily bolus
      of 12.5-75 micrograms of baclofen through a reservoir, improvement of mentation
      and speech conditions, marked improvement of dystonic and abnormal movements of
      the upper limbs and trunk and a notable reduction of hypertonia were observed in
      all cases, which led to a better performance of motor activities in skilled acts
      and transfer. With these preliminary results in mind, in all cases the previous
      cervical subarachnoid catheter was attached to a programmable pump that infused a
      daily total dose varying from 100 to 190 micrograms of baclofen in a continuous
      or multistep complex mode. After a mean follow-up of 21 months previous results
      were long-lasting. Neither overdose side effects nor malfunction of the system
      were observed.

PMID- 7631055
TI  - Stereotactic neural transplantation.
AB  - In this keynote address, the author presents state-of-the-art information on the
      current status of the transplantation of fetal tissue for the treatment of
      movement disorders. Drawing on the experience in his own studies and elaborating
      upon the work reported by others, he outlines specific techniques and protocols
      and summarizes early findings.

PMID- 7631057
TI  - Long-term follow-up results of stereotactic adrenal medullary transplantation in
      Parkinson's disease.
AB  - Stereotactic adrenal medullary transplantation into the striatum was performed in
      5 patients with severe Parkinson's disease. Four patients had previously been
      treated with thalamotomies and all were on L-dopa therapy with significant side
      effects. All 5 patients had shown marked disability before the procedure.
      Autologous adrenal medullary tissue was sliced into 20-30 fragments and
      transplanted into two sites of the caudate nucleus, one at the ventricular
      surface and the other in the head of the nucleus. The cases were followed for 4-5
      years (mean 4.5 years), except for 1 patient who died of unrelated causes 22
      months after the procedure. Initial bilateral symptom improvement was observed in
      all cases for 9-21 months (mean 15.2 months) after transplantation without L-dopa
      therapy. Later, these improvements progressively deteriorated. L-dopa therapy had
      to be resumed for all. MRI on the long-term follow-up showed the transplanted
      tissue as a low signal intensity area surrounded by high intensity spots in T1-
      and T2-weighted images. Compared to previous MR studies, the transplanted tissue
      was shrunken and presumed nonviable.

PMID- 7631056
TI  - Transplantation of fetal mesencephalic tissue in Parkinson's patients.
AB  - Patients with idiopathic Parkinson's disease who had become refractory to medical
      treatment underwent unilateral stereotactic transplantation of mesencephalic
      tissue obtained from 7- to 9-week-old postconception fetuses. Small pieces of
      tissue, less than 1 mm, were deposited in 9 sites in the putamen and 3 in the
      caudate. Patients were 4 men and 3 women and aged from 42 to 59 years (mean 50).
      Symptom durations were from 9 to 21 years (mean 14). The examinations were done
      at 3- to 4-month intervals pre- and postoperatively. Patients were examined for a
      minimum of 1 year postoperatively. The examinations consisted of neurological and
      general physical examinations, UCLA Parkinson's Disability Scale, Hoehn and Yahr
      rating and United Parkinson's Disease Rating Scale (PDRS), all in both 'on' and
      'off' states. Video recordings and timed tests of a number of motor tests were
      performed. Patients also completed 7 consecutive days of hourly self-assessments
      prior to each visit. Fluorodopa PET scans were obtained pre- and 6 and 15 months
      postoperatively. The operations took place from mid-July 1992 to January 1993.
      Postoperative states have been free of complications. All have been on
      immunosuppressants. Levodopa was transiently decreased in the postoperative
      period, but raised to approximately the preoperative level thereafter. In late
      March 1993, 3 patients appeared to show modest improvement in the UCLA and UPDRS
      scales and in the patients' self-assessments.

PMID- 7631058
TI  - Stereotactic retransplantation in Parkinson's disease: clinical, imaging and
      electrophysiological evidence of adrenal brain graft viability.
AB  - In March 1993, a patient with idiopathic Parkinson disease who had received an
      adrenal brain autograft 6 years before underwent bilateral stereotactic
      transplantation of a mesencephalic cell suspension into the striatum, in order to
      prevent further deterioration in his neurological condition. During the CT-guided
      surgical planning and the transplantation procedures, electrophysiological
      evidence of the adrenal graft viability was assessed. Based on these findings, we
      drew the preliminary conclusion that the chromaffin tissue implanted in April
      1987 is still functional, which explains the clinical evolution of this patient
      during the postoperative long-term follow-up.

PMID- 7631059
TI  - In memoriam Professor Edward Robert Hitchcock. NECTAR members.

PMID- 7631060
TI  - Plasticity in human somatosensory thalamus as a result of deafferentation.
AB  - Experimental studies indicate that deafferentation results in reorganization of
      the somatosensory map at various levels of the CNS, such that the representation
      of a body part adjacent to a region that is denervated expands into the
      deafferented area. Recent data suggest that in the human this occurs at the
      cortical level, but subcortical structures have not been systematically
      investigated. To test the hypothesis that the human thalamus is capable of
      significant reorganization as a result of changes in afferent input,
      microelectrode recording and stimulating techniques were used to define thalamic
      somatotopy in 61 patients undergoing stereotactic procedures. Five groups were
      compared: those with pain in the deafferented body part, face (n = 9), arm/hand
      (n = 4), leg/foot (n = 8) and hemibody (n = 5) and those with neither pain nor
      deafferentation, i.e., movement disorder (n = 24). Trunk representation, as
      determined from receptive fields, was significantly larger in patients with
      leg/foot deafferentation than in patients without deafferentation (1.8 +/- 0.7
      vs. 0.5 +/- 0.2 mm; p < 0.01). Also, microstimulation induced paraesthesiae in
      the face from a significantly larger region of thalamus in the facially
      denervated group compared to the movement disorder group (13.8 +/- 2.8 vs. 3.7 +/
      0.6 mm; p < 0.001). There were no significant differences in the representation
      of other body parts in the five groups. The results in the leg-deafferented group
      agree with conclusions reached from animal studies; however, the human situation
      is more complex. There appear to be different patterns and degrees of somatotopic
      reorganization in the human, all of which may be associated with pain syndromes.

PMID- 7631062
TI  - The new age of stereotaxis: toward the 21st century.
AB  - The remarkable recent progress in stereotactic surgery, functional as well as
      nonfunctional, is briefly reviewed, with emphasis on our own experiences. Owing
      to the day-by-day progress of computer-assisted neuroimaging and basic research
      in neuroscience, stereotactic surgery has greatly benefitted. In this sense, the
      future of stereotactic surgery could be 'en rose' and quite promising toward the
      21st century.

PMID- 7631061
TI  - Intraoperative monitoring of spinal cord SEPs during microsurgical DREZotomy
      (MDT) for pain, spasticity and hyperactive bladder.
AB  - Since 1972, MDT has been performed in 234 patients with chronic pain, 140 with
      hyperspasticity and 12 with hyperactive neurogenic bladder. In the last 64
      patients, the evoked electrospinogram has been recorded intraoperatively from the
      surface of the spinal cord, to monitor the electrophysiological effects produced
      by the surgical lesioning, not only on the conduction of lemniscal fibers when
      entering the dorsal column, but also on the postsynaptic responses of the dorsal
      horn cells. The decrease in amplitude of the latter responses (N13 or N22) was
      well correlated with (1) the depth and the width of the DREZ lesion, and (2) the
      number of spinal segments operated on. In most cases, amplitude was reduced in
      the order of 2/3, which was considered the best value.

PMID- 7631063
TI  - High-cervical spinal cord electrical stimulation in brain low perfusion
      syndromes: experimental basis and preliminary clinical report.
AB  - Previous studies of our group showed that C1-C2 spinal cord stimulation increases
      carotid and brain blood flow in normal conditions in the goat and dog and it has
      a beneficial vasomotor effect in a model of vasospasm in the rat. For further
      clinical application it seemed rational to investigate the possible vascular
      changes mediated by this technique in experimental brain infarction. To this aim,
      45 New Zealand rabbits were used. Brain infarction was produced by bilateral
      carotid ligation in 15, unilateral microcoagulation of the middle cerebral artery
      in 15 and by microcoagulation of the vertebral artery at the craniocervical
      junction in the other 15. One week later, following daily clinical scoring and
      cortical and posterior fossa blood flow readings by laser Doppler, a period of
      120 min of right C1-C2 spinal cord electric stimulation was performed. A mean of
      27% increase in previous blood flow recordings was obtained at the right
      hemisphere and a mean of 32% in the posterior fossa. This procedure was used in
      10 patients presenting with various cerebral low perfusion syndromes. Though not
      constant, an increase in alertness, retention, speech, emotional lability and
      performance in skilled acts was achieved. No MR changes were observed, though
      SPECT readings showed an increase in blood flow in the penumbral perilesional
      area.

PMID- 7631064
TI  - Cerebral blood flow and somatosensory evoked response changes induced by spinal
      cord stimulation: preliminary follow-up observations.
AB  - A group of 6 patients undergoing cervical spinal cord stimulation (SCS) because
      of different pathologies was studied. Multipolar leads (QUAD-Medtronic) were
      inserted percutaneously; following an SCS test period, leads were connected to a
      multiprogrammable, fully implantable generator (ITREL II). Neither surgical nor
      other side effects were found. Regional cerebral blood flow (rCBF) (xenon-133
      inhalation) was determined in the basal condition and after 30 min of SCS.
      Somatosensory-evoked potential (SSERs) from the legs were recorded in basal
      conditions and after 45 min of SCS. In 2 patients SSERs could not be evaluated
      due to electrical noise from SCS. CBF increased mainly in anterior regions in 4/6
      patients (P300 improved in 1 of them and in another case), and was unchanged in 2
      patients. rCBF was retested after a mean of 9.5 months of continuous SCS with the
      same parameters. rCBF returned to basal values in the 4 patients showing an early
      flow increase; in contrast, rCBF increased in the other 2 cases without early
      flow changes. These preliminary data seem to support the view of an acute effect
      of SCS on rCBF as well as on SSER, at least in some patients. Differences in long
      term rCBF modifications might depend on either the underlying pathology or on the
      different neuronal system involved by SCS.

PMID- 7631065
TI  - Spinal cord stimulation and cerebral blood flow: an experimental study.
AB  - Spinal cord stimulation (SCS) affects peripheral, coronary and cerebral blood
      flow (CBF) in humans. In 1986 Meglio et al. [Appl Neurophysiol 1986;49:139-146]
      advocated a functional reversible sympathectomy as one of the mechanisms of SCS
      in man. An experimental animal model was developed to study SCS effects on CBF
      and to investigate the possible mechanisms. Twenty-one white New Zealand rabbits
      were anesthetized with Fluothane; spontaneous ventilation was permitted. A steady
      hemodynamic and metabolic state was maintained. A small cervical laminectomy was
      performed and an electrode (Medtronic Sigma 3483) was placed in the epidural
      space over the posterior spinal cord. Both common carotid arteries were exposed
      and external carotid arteries were ligated. In 3 animals, the cervical
      symapthetic trunk (CST) was exposed and wrapped with bipolar hook-stimulating
      electrodes. SCS was performed for 20 min with electrical square waves of 210
      microseconds duration, 80 cycles/s, at 2/3 motor threshold intensity. CST
      stimulation was delivered for 1 min with the following parameters: 10 V, 10
      cycles/s, 0.5 ms duration. CBF velocities of both internal carotid arteries were
      measured by using a CW Doppler (in all the animals) and electromagnetic flowmeter
      (in 2 animals), at rest, during sympathetic trunk stimulation, during SCS, during
      simultaneous SCS and CST stimulation. During SCS, an increase of CBF was detected
      in 11 rabbits (52.4%); a decrease was observed in two cases (9.5%). No change was
      detected in the remaining 8 animals (38%). CST stimulation induced a decrease of
      CBF in all animals. Electromagnetic flowmetry confirmed velocitometric findings
      in the 2 cases studied.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7631066
TI  - Visualization of dopamine nerve terminals in monkey by positron emission
      tomography using 4-[18F]fluoro-L-m-tyrosine.
AB  - 4-[18F]Fluoro-L-m-tyrosine (FMT) is an L-Dopa analog that essentially follows the
      L-Dopa metabolic pathway, but without 3-O-methylation or extensive peripheral
      metabolism. As such, FMT may serve as a useful probe of striatal dopaminergic
      function with positron emission tomography (PET). FMT was synthesized, as
      previously described by Perlmutter et al. [Appl Radiat Isot 1990;41:801-807].
      Scanning was undertaken with the SHR2000 positron tomograph (image spatial
      resolution, 3.5 x 4.5 x 6.5 mm). Two Macaca monkeys were anesthetized with
      ketamine (10 mg/kg) and pentobarbital (20 mg/kg). FMT was administered
      intravenously (5-6 mCi; specific activity 1-2 Ci/mmol) following carbidopa
      pretreatment (5 mg/kg i.v., 60 min before FMT administration). Dynamic image
      acquisition was done for 2 h immediately after tracer injection. This emission
      acquisition involved twelve 2-min frames followed by nine 4-min frames, and six
      10-min images. Arterial blood samples were collected according to a schedule for
      assay of plasma [18F] radioactivity. Specific uptake of FMT in aromatic L-amino
      acid-decarboxylase-rich areas of the monkey striatum was observed with PET
      imaging. The striatum-to-cerebellum ratio of the accumulation increased over time
      to 3.0 at 2 h. These results show the promise of FMT as a PET tracer in
      evaluating the CNS dopaminergic system.

PMID- 7631067
TI  - Professor Edward Robert Hitchcock.

PMID- 7631068
TI  - CT-oriented microrecording guided selective thalamotomy.
AB  - A further trial of CT-oriented microrecording guided stereotactic selective
      thalamotomy was conducted at the Centro Internacional de Restauracion
      Neurologica, Havana City as treatment of resting tremor in 11 patients with
      idiopathic Parkinson's disease (PD), and in 3 other patients with intentional
      tremor associated with multisystemic atrophy and cerebral palsy. Three of the
      parkinsonian patients had undergone fetal mesencephalic tissue transplantation
      with significant improvement of the most debilitating symptoms of PD and
      stabilization of the motor state, but predominantly unilateral tremor had
      impaired them progressively despite increased levodopa doses. A Leksell frame was
      used with a novel surgical planning system and electrophysiological recordings to
      identify the optimal target point inside the ventralis intermedius. In all but 1
      case, the tremor was totally arrested. No persistent complications were observed.

PMID- 7631069
TI  - Neurotransplantation in Parkinson's disease: from open microsurgery to bilateral
      stereotactic approach: first clinical trial using microelectrode recording
      technique.
AB  - This paper summarizes the results of three controlled clinical trials related to
      the transplantation of embryonic ventral mesencephalic tissue into the striatum
      of 46 idiopathic parkinsonian patients exhibiting motor complications on standard
      levodopa therapy. From January 1988 to April 1990, 30 subjects with fluctuating
      Parkinson's disease received fetal dopaminergic tissue implants by the open
      microsurgical technique. In March 1992 the stereotactic approach was adopted for
      successive fetal mesencephalic cell suspension transplants (7 unilateral and 9
      bilateral) into the caudate and putamen of parkinsonian patients with levodopa
      induced complex fluctuations and dyskinesias. The neurological assessment
      performed 12 months before and 3-18 months after transplantation demonstrated a
      reduction of both the daily time spent in the 'off' condition and the number of
      daily 'off' periods, and a significant improvement of the motor scale. The
      stereotactic selective thalamotomy with microelectrode recording was introduced
      in January 1993, in order to provide a further potential treatment strategy;
      i.e., the combination of the two surgical trends in Parkinson's disease, the
      restorative neurotransplantation technique, and the selective lesional approach.
      In addition to that, microelectrode recording is also used for implantation site
      selection and functional characterization.

PMID- 7631070
TI  - Epilepsy: principles of surgical management.
AB  - In his keynote address, the author reviews early work in the surgical management
      of the epilepsies and presents a state-of-the-art review of current basic science
      and clinical indications for and results from corpus callosotomy for the
      treatment of seizure disorders.

PMID- 7631071
TI  - Surgical treatment of complex partial seizures: 20 years' experience.
AB  - From 1972 to 1992 inclusive, the author performed 263 surgical procedures for the
      relief of intractable epilepsy. The purpose of this report is to review 112
      temporal lobectomies for the treatment of drug-resistant complex partial
      seizures. There were 90 adults and 22 children, in whom there were 61 left-sided
      procedures and 51 right-sided ones. All these cases represent 10% of 2,676
      epileptics seen at the Osler Clinic during the last 20 years. The results were
      evaluated in four groups: 60 patients belonging to group A were seizure-free,
      group B comprised 24 patients with a reduction in seizures of 75%, group C which
      included 17 cases had minimal improvement, and finally group D with 11 patients
      showed no improvement at all. The factors of good surgical outcome were analyzed
      in 60 patients. The total number of patients that substantially improved after
      surgery represented 74.5% of the whole series with no mortality and a morbidity
      of 1.8%.

PMID- 7631072
TI  - Invasive intracranial monitoring, cortical resection and multiple subpial
      transection for the control of intractable complex partial seizure of cortical
      onset.
AB  - Invasive intracranial monitoring with subdural grids has led to a greater
      appreciation of cortical function and the discovery of ictal onset either
      independently or in conjunction with deep structures. With the description of
      multiple subpial transections the armamentarium for surgical control of
      intractable seizures has been expanded. Utilizing invasive intracranial
      monitoring with subdural grids and strips, a large series of patients with
      intractable complex partial seizures originating in exquisite cortex, and in some
      cases additionally in deep structures, have undergone surgery. These patients
      would previously have been judged not to be candidates for surgical control of
      seizures. We will present 9-month or greater follow-up in an ongoing series of
      patients undergoing cortical resection and subpial transections in whom there has
      been a statistical improvement in control or alleviation of their seizure
      disorder. The report will specifically discuss outcomes as related to exquisite
      cortex, motor, sensory and language functions, as well as clinical results and
      EEG.

PMID- 7631073
TI  - Subdural recording and electrical stimulation for cortical mapping and induction
      of usual seizures.
AB  - Chronic subdural strip electrodes were used for recording of seizure origin,
      cortical mapping and confirmation of seizure foci by electrical stimulation.
      Seventeen patients were comprehensively evaluated for epilepsy surgery. All
      patients had failed medical treatment. Intracranial recording was necessary in 12
      patients. Speech area was determined in 50% of the patients stimulated. Seizure
      origin was confirmed by stimulation-induced usual seizures or aura in 75% of the
      patients stimulated. Intracranial chronic recordings were safe and added
      important prognostic information, as well as helped decide the extent of
      resection.

PMID- 7631074
TI  - Comparing the extent of hippocampal removal to the outcome in terms of seizure
      control.
AB  - The relationship between the outcome of temporal lobectomy for epilepsy and the
      size of the hippocampectomy tailored to intraoperative electrocorticographic
      findings was evaluated in 52 patients, with at least 1 year of follow-up. In 22
      patients, < 2.0 cm of hippocampus was removed. Postoperatively, 16 (72.7%) were
      class I (seizure-free), 3 (13.6%) were class II (rare seizures) and 3 (13.6%)
      were class IV (no worthwhile improvement). In 30 patients, > or = 2.0 cm of
      hippocampus was removed, and the results were as follows: 21 (70%) were class I,
      4 (13.3%) were class II, 1 (3.3%) was class III (worthwhile improvement) and 4
      (13.3%) were class IV. Statistically significant differences were not present.

PMID- 7631075
TI  - Role of multichannel magnetoencephalography in the evaluation of ablative seizure
      surgery candidates.
AB  - Magnetic source imaging (MSI) was performed on 30 ablative epilepsy surgery
      candidates. The technique involved high resolution multiplanar MRI images with
      lipid fiducials attached to the patient's head to define a head-based 3D
      coordinate space. Magnetoencephalography (MEG) was performed after digitizing the
      same fiducial points. A 37-channel magnetometer obtained data at two to five
      sites over each hemisphere. MEG epileptiform data were obtained with and without
      EEG triggering. A single equivalent current dipole model was used to determine
      orientation and location of a dipole generator whose surface isocontour map most
      closely fits the measured dipolar data for each event. The MEG data were then
      transformed to MRI images for source localization. In five of seven cases with
      ictal anterior temporal lobe foci, MSI data were localized to the same temporal
      lobe but did not provide additional spatial data. In 10 of 11 cases with
      convexity foci, MSI provided additional spatial localizing data. MSI did not
      verify depth electrode localization in one anterior temporal-orbital frontal and
      three orbitofrontal cases. In seven of eight cases in which depth EEG recordings
      were nonlocalizing, MSI provided insufficient localizing data. MSI appears to
      provide additional spatial localizing data in most cases with a convexity
      epileptic focus.

PMID- 7631076
TI  - Multichannel magnetoencephalographic mapping of sensorimotor cortex for epilepsy
      surgery.
AB  - Preliminary reports have shown a close correlation between the anatomic location
      of evoked magnetic somatosensory fields and intraoperative evoked somatosensory
      potentials in patients with mass lesions. We have performed magnetic source
      imaging (MSI) of sensory and motor (MER) evoked responses or fields on 4 patients
      with frontal convexity epileptic foci. The method involves (1) graphic overlaying
      of magnetoencephalography evoked field data and three-dimensional (3D) phase
      contrast magnetic resonance angiographic data on 3D MRI surface cortical
      renderings, and (2) correlating these data with intraoperative stimulation-mapped
      sensory and/or motor responses and local cortical venous anatomy. Our initial
      results indicate that the location of MSI evoked sensory data correlates closely
      with the results of intraoperative stimulation mapping. MSI MERs have tended to
      show a less discrete spatial topography, involving areas of cortex extending
      beyond the motor strip.

PMID- 7631077
TI  - An experimental animal model of spinal cord stimulation for pain.
AB  - In spite of the routine usage of spinal cord stimulation (SCS) as treatment of
      chronic pain, there is an insufficient understanding of the mechanisms underlying
      its effect. The method was originally developed as a spin-off from experiments
      demonstrating the inhibitory control of nociceptive signals by the activation of
      large afferent fibers, and on the basis of these findings the gate-control theory
      was advanced. Later experiments showed that stimulation of the dorsal columns can
      inhibit the relay of nociceptive impulses to second-order neurons in the dorsal
      horn. It should be emphasized that all these experiments were performed with
      acute noxious stimuli; it is now universally recognized that SCS in patients is
      preferentially, or exclusively, effective for chronic neuropathic types of pain.
      For these and other reasons the mode of action of SCS in clinical pain cannot be
      inferred from these early animal experiments. In ongoing studies we have used
      animal models of mononeuropathy (rat) in which we have applied SCS acutely or
      chronically with stimulation parameters similar to those used in patients. In
      these animals the first component of the flexor reflex appears with a lower
      stimulus threshold in the nerve lesioned than in the intact, sham-operated leg.
      SCS was applied at the approximate level of Th-XII during 10-20 min and produced
      a marked augmentation of the stimulus threshold. This abnormally high threshold
      was not normalized until 30-60 min after the end of SCS. In awake animals SCS was
      applied via an implanted spinal electrode and the effect on behavior changes
      associated with mononeuropathy was studied.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7631078
TI  - Stereotactic neurosurgery in Mexico.
AB  - In his 'Honored Guest' lecture, the author details his long and distinguished
      career as a pioneer in stereotactic and functional neurosurgery, with particular
      emphasis on his early work in introducing stereotactic techniques into Mexico and
      his efforts to use his international reputation to disseminate information
      worldwide.

PMID- 7631079
TI  - Spinal cord stimulation in low back and leg pain.
AB  - We have reviewed our experience with spinal cord stimulation (SCS) in patients
      with low back and leg pain. 33 patients complaining of leg and low back pain
      underwent percutaneous tests of SCS. 28 patients had failed back surgery
      syndromes, 1 patient had pain related to an L1 vertebral body fracture, another
      from Tarlow cysts and the remaining 3 patients had lumbosacral spondyloarthrosis
      and osteoporosis without radiological signs of root compression. 28 patients
      showed mono- or pluriradicular deficits. At the end of the test period (5-65
      days), 21 patients (63.6%) reported more than 50% of pain relief (mean analgesia
      75%) and were submitted to chronic stimulation. The mean follow-up was 45.5
      months. At maximum available follow-up, 40% of the patients (13 out of the 33
      initial patients) were successfully using the stimulator (mean analgesia 66.6%).

PMID- 7631080
TI  - A prospective, randomized study of spinal cord stimulation versus reoperation for
      failed back surgery syndrome: initial results.
AB  - Spinal cord stimulation (SCS) has been reported to be effective treatment for the
      failed back surgery syndrome in a number of retrospective case series. Its
      retrospectively reported results compare favorably with those of neurosurgical
      treatment alternatives, such as reoperation and ablative procedures. There has
      been no direct prospective comparison, however, between SCS and other techniques
      for pain management. We have undertaken a prospective, randomized comparison of
      SCS and reoperation in patients with persistent radicular pain, with and without
      low back pain, following lumboscral spine surgery. Patients selected for
      reoperation by standard criteria have been randomly assigned to initial treatment
      by one or the other technique. The primary outcome measure is the frequency of
      crossover to the alternative procedure, if the results of the first have been
      unsatisfactory after 6 months. Results for the first 27 patients reaching the 6
      month crossover point show a statistically significant (p = 0.018) advantage for
      SCS over reoperation. This is one of many potentially important outcome measures,
      which are to be followed long-term as a larger overall study population accrues.

PMID- 7631081
TI  - Italian multicentric study on pain treatment with epidural spinal cord
      stimulation.
AB  - A multicentric study on the treatment of nonmalignant chronic pain with epidural
      spinal cord stimulation (SCS) has been carried out in 32 Italian centers devoted
      to pain therapy. Neurosurgical and anesthesiology units participated in this
      retrospective study. 410 of the eligible patients were enrolled in the protocol:
      48% were male, 52% female. All patients underwent a screening test period
      (average 21 days) and 74% underwent the definitive implant. The diagnosis was
      failed back surgery syndrome in 45%, reflex sympathetic dystrophy in 15%, phantom
      limb pain in 14%, postherpetic neuralgia in 8%, peripheral nerve injury in 5%,
      others 13%. 84% received noninvasive unsuccessful treatment (10 tensor
      acupuncture). All had previous pharmacological therapy which was not always
      discontinued when SCS took place. Pain assessment had been done with the visual
      analog scale and verbal scale both subjectively and by the physician and nurses.
      Neuropsychological profile with minimal mental test or MMPI was obtained in 68%
      of the patients. These results were favorable (i.e. excellent or good; more than
      50% reduction of pain) in 87% of the patients at the 3-month follow-up, 75% at
      the 6-month follow-up, 69% at the 1-year follow-up, and 58% at the 2-year follow
      up. Complication rate was: dislocation of the electrocatheter 4%, technical
      problems 3%, infections of the system 2%. The results will be discussed in
      correlation with the different etiologies of the nonmalignant chronic pain
      syndrome.

PMID- 7631082
TI  - Analgesic action of acute and chronic intraspinally administered opiate and alpha
      2-adrenergic agonists in chronic neuropathic pain.
AB  - Intrathecal (IT) administration of opiate analgesics has become a popular method
      of pain control in patients with pain of both malignant and nonmalignant origin.
      Therapeutic efficacy for nonmalignant pain states might be improved by having a
      broader range of available pharmacologic agents for intrathecal administration.
      Toward this aim, we have applied a new model of neuropathic pain in the rat to
      evaluate the relative analgesic efficacy and potential cross tolerance of both
      acutely and chronically administered IT morphine (MS) and tizanidine (TZ), an
      alpha 2-adrenergic agonist. Under anesthesia, 225 Sprague-Dawley male rats
      underwent unilateral multiple partial suture ligation of the sciatic nerve. This
      produces a syndrome similar to human neuropathic pain. Chronic lumbar IT cannulae
      were placed via the cisterna magna. Seven days after surgery, animals were tested
      for spontaneous ambulation and paw pinch tolerance. These tests correlate with
      human clinical observations of chronic pain and hyperpathia. For the acute drug
      administration, animals were then given saline, 10, 20, or 30 micrograms IT MS or
      10, 25 or 50 micrograms IT TZ and testing was repeated. Preliminary results
      suggest that MS, in a dose-dependent manner, significantly decreased abnormal
      limb withdrawal from the floor while ambulating and increased paw pinch
      withdrawal latency to cutoff values (p < or = 0.01 in all tests). IT MS had
      significant effects on pain sensation in the operated and unoperated limbs,
      increasing latencies to cutoff and nonspecifically inhibiting pain transmission.
      IT TZ had a similar effect on decreasing limb withdrawal from the floor, but paw
      pinch withdrawal latency was increased only to the normal range, not to cutoff
      values. These effects were also dose-dependent. For chronic drug administration,
      after baseline testing, osmotic minipumps (Alza, Palo Alto, Calif.) delivering
      either saline, 60 or 120 micrograms/day MS, or 75 or 150 micrograms/day TZ were
      attached to the IT catheter. Testing was done on days 1, 4, 7 and 14 after pump
      attachment. On day 14, the animals were given an IT bolus of the noninfused drug
      (50 micrograms tizanidine or 30 micrograms morphine) and the tests were repeated
      to determine degree of cross tolerance. Initially, chronic MS and TZ
      administration produced a similar degree of analgesia seen with results obtained
      with acute administration. The animals rapidly became tolerant to these agents so
      that by day 4, neither drug had an analgesic effect. No significant cross
      tolerance between MS and TZ was observed. Thus, both IT MS and TZ are analgesic
      in experimental chronic neuropathic pain.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7631083
TI  - The history of stereotactic neurosurgery.
AB  - In his keynote address, the author presents a detailed history of the development
      of stereotactic and functional neurosurgery worldwide, with particular emphasis
      on the pioneering scientist in the field. He outlines the early days of
      stereotaxis in North and South America, Europe and Asia and supplements his
      history with an extensive list of early references.

PMID- 7631084
TI  - Neurons with high-frequency discharge in the central nervous system in chronic
      pain.
AB  - Prior to implantation of the thalamic- or motor cortex-stimulating electrodes for
      relieving chronic pain, extracellular unitary activity was recorded and local
      microstimulation was done, by using microelectrodes, mainly in the ventral caudal
      nucleus of the thalamus. A significant number of high frequency discharge neurons
      (hyperactive neurons) were recorded and showed three types of discharge patterns
      with different interval histograms. In animal experiments, unilateral dorsal root
      sectioning from C5 to Th1 of male Wistar rats was made according to the method of
      Lombard et al[4]. One to three months after the operation, cellular activity was
      recorded from the contralateral thalamic nuclei (VP, zona incerta), lemniscus
      medialis and striatum. Hyperactive neurons were recorded from the thalamic nuclei
      and lemniscus medialis. The firing patterns and distribution of hyperactive
      neurons in these animals were very similar to those of humans. Hyperactive
      neurons were examined via electrical stimulation of and/or iontophoretical
      application of chemical substances. Hyperactive neurons were unaffected by
      electrical stimulation of the nucleus raphe dorsalis and locus ceruleus. However,
      sensorimotor cortical stimulation showed a reduction of firing in the hyperactive
      neurons. Iontophoretic application of glutamate showed increase in firing and
      GABA showed remarkable firing suppression. These results suggested that
      hyperactive neurons of the thalamic nuclei receive a facilitatory effect from the
      sensorimotor cortex with little influence from adrenergic or serotonergic
      systems, and these neurons have a relationship to the glutamatergic and GABAergic
      fibers or receptors.

PMID- 7631085
TI  - Chronic motor cortex stimulation for central deafferentation pain: experience
      with bulbar pain secondary to Wallenberg syndrome.
AB  - Six patients with bulbar pain caused by lateral medullary infarct were treated by
      stimulation therapy. Dysesthesia on the opposite side of the body was subjected
      to stimulation therapy in these patients. Of the subjects, 4 underwent thalamic
      stimulation and 3 were treated by motor cortex stimulation; the effects of both
      thalamic and motor cortex stimulation were investigated in 1 patient. No
      satisfactory pain control was obtained by thalamic stimulation in any of the
      patients in this series. In contrast, 2 of the 3 patients treated by motor cortex
      stimulation reported satisfactory pain control. The pain inhibition usually
      occurred at intensities below the threshold for the production of muscle
      contraction (pulse duration, 0.1-0.5 ms; intensity, 3-8 V). This finding was
      consistent with our previous observations made in a series of patients with
      thalamic pain, indicating that motor cortex stimulation is significantly more
      useful than thalamic stimulation for controlling deafferentation pain secondary
      to central nervous system lesions. We discuss the possibility that better control
      of deafferentation pain may be provided by stimulation at a level more rostral to
      the site of deafferentation.

PMID- 7631086
TI  - Pathophysiology of central (thalamic) pain: combined change of sensory thalamus
      with cerebral cortex around central sulcus.
AB  - In 13 patients with central (thalamic) pain after stroke, CT, MRI, PET scan and
      intraoperative thalamic microrecordings were performed. Electrophysiological
      studies showed that irregular burst discharges were often encountered in the
      posterolateral thalamus. The more often the irregular burst discharges were
      encountered, the greater the decrease of sensory response in the posterolateral
      thalamus. Metabolic studies showed that regional cerebral glucose metabolism
      decreased in both the posterolateral thalamus and in the cortical postcentral
      area on the lesioned side in all cases. In the thalamic lesion cases in which
      many irregular burst discharges were found in the posterolateral thalamus,
      regional cerebral glucose metabolism and the relative value of glucose to oxygen
      metabolism increased in the cortical precentral area on the lesioned side. It was
      suggested that decreased activity with abnormal burst discharge in the
      posterolateral (sensory) thalamus associated with changes in cortical activity
      adjacent to the central sulcus might be related to the genesis of central
      (thalamic) pain. It is emphasized that cortical activity decreased in the
      postcentral area, but often increased in the precentral area.

PMID- 7631087
TI  - Evaluation of patients with atypical trigeminal neuralgia for permanent electrode
      implant by test stimulation of the ganglion gasseri.
AB  - The treatment of so-called atypical trigeminal neuralgia, characterized by long
      lasting burning pain sensations without any pain attacks was for a long time an
      unsolved problem in contrast to the so-called 'tic douloreux'. Following the
      experience with our own patients and other groups, destructive procedures in
      atypical trigeminal neuralgia frequently result in worsening of the clinical
      conditions. We have therefore transferred the well-established method in the
      periphery of therapeutic electrostimulation to the trigeminal region. The
      evaluation of the patients with atypical trigeminal neuralgia is the key for good
      therapeutic results. Therefore percutaneous test stimulation of the ganglion
      gasseri has to be performed during a hospital stay. 54% of 149 patients
      experienced pain relief during test stimulation. Therefore in 81 patients with
      positive test results, electrodes were implanted together with a neurological
      pulse generator (Itrel Medtronic).

PMID- 7631088
TI  - Ventroposterolateral pallidotomy.
AB  - Recent laboratory experiments have produced increasing evidence that nigral
      striatal dopamine deficiency causes an inhibitory hyperactivity in the medial
      globus pallidus (MGP), where it freezes the initiation of movement and thus
      causes bradykinesia, rigidity and tremor. Surgical lesions in the
      ventroposterolateral (VPL) pallidum in man not only improve the parkinsonian
      bradykinesia, but also the tremor, rigidity, and the L-dopa-induced dyskinesias
      disappear or diminish. The present study shows that VPL pallidotomy improves
      several psychomotor functions, such as walking speed and manual dexterity. Right
      sided VPL thalamotomy also increases the speed and accuracy in verbal
      performance. Ventrolateral thalamotomy increases bradykinesia. The findings
      support the concept that the parkinsonian symptoms in man develop in the MGP.
      Intact pathways from MGP via thalamus to the premotor and motor cortex seem
      necessary for normal motor functioning. The author also discusses the mechanisms
      of pallidotomy and thalamotomy.

PMID- 7631089
TI  - Anatomic and physiological considerations in pallidotomy for Parkinson's disease.
AB  - Our ongoing study of central pallidotomy for the control of Parkison's disease in
      selected patients has provided the opportunity to explore the topographical and
      somatotopic organization of the human globus pallidus. Utilizing microelectrode
      techniques we have obtained recordings which were correlated with data from MPTP
      parkinsonian primates. In addition, we performed pre- and postoperative FDG/PET
      scans in these patients. Our studies reveal similarities between the MPTP
      parkisonian primate model and human Parkinson's disease in terms of physiological
      recordings and responses. However, we have encountered significant differences
      between dominant and nondominant hemisphere representations, particularly for the
      hand, in the human. In addition, our PET studies confirmed, as in previous
      parkinsonian primate models, glucose hypermetabolism in the lenticular area of
      Parkinson's disease patients. This hypermetabolism is dramatically altered by
      creation of a lesion in the globus pallidus medialis. This is demonstrated by
      follow-up PET scans which reveal not only a decrease in metabolism of the
      operated lenticular region, but also in the frontal cortical projections. These
      combined observations of the cellular activity in globus pallidus and the
      observed changes in PET metabolism support the selection of the pallidum for
      lesioning and control of Parkinson's disease, and offer insight into the
      underlying physiology of this disorder. The above physiological and PET data will
      be clinically correlated with our ongoing series of 35+ patients.

PMID- 7631090
TI  - Peri- and postoperative magnetic resonance imaging localization of pallidotomy.
AB  - Postoperative magnetic resonance imaging (MRI) of basal ganglia functional
      lesions illustrates the accuracy of preoperative target localization. The
      technique of perioperative MRI and CT localization for pallidotomy will be
      discussed and correlated with the center of the lesion on postoperative standard
      MRI as well as three-dimensional (3-D) volume acquisition of image. Using a 1.5
      tesla Signa system, a conventional acquisition of 128-slice, 256 x 256 matrix
      spoiled grass (SPGR) images were used for 3-D reformation. This allowed
      approximately 1 x 1 x 2 mm resolution over a 24-cm field of view in a T-1
      weighted image. The display affords a volumetric analysis of the anatomic
      location and relation of the post-ventral pallidotomy to adjacent structures.
      Accuracy lesion placement based on perioperative MR coordinates and revealed on
      postoperative images is confirmed. The volume of the lesion as well as its
      location are factors that affect clinical outcome.

PMID- 7631091
TI  - Chronic electrical stimulation of the VL-VPL complex and of the pallidum in the
      treatment of movement disorders: personal experience since 1982.
AB  - Since 1982, we have been able to control involuntary movements associated with
      deaf-ferentation by means of chronic electrical stimulation of the thalamic
      sensory nucleus through implanted programmable neuropacemakers. Since 1987, we
      have been using the same system with electrodes chronically implanted in the VL
      for treating selected cases of tremor due to Parkinson's disease, multiple
      sclerosis and in cases of essential tremor. In our series of 60 patients,
      suppression of tremor was achieved in almost all cases; however, due to
      dysarthria in 30% of the cases (cases after previous thalamotomy in the other
      side or with bilateral stimulation), the amplitude of stimulation was corrected
      and thus some tremor was still observed. The rigidity of parkinsonism was in all
      cases improved. One case of hemiballism was perfectly controlled with the same
      technique. Finally, 3 cases of Parkinson's disease with severe hypokinesia,
      speech and gait disturbances, and on-off phenomenon have been globally improved
      by a bilateral chronic stimulation of the pallidum.

PMID- 7631092
TI  - Acute and long-term effects of subthalamic nucleus stimulation in Parkinson's
      disease.
AB  - In animal models of Parkinson's disease (PD), it is postulated that the excessive
      output from the subthalamic nucleus (STN) plays a critical role. Selective
      lesions or high frequency electrical stimulation of the STN can alleviate
      parkinsonian symptoms in MPTP-treated monkeys. We decided to carry out STN
      stimulation in patients suffering from severe akinetic forms of PD. After
      approval of the institutional ethical committee, we operated on a parkinsonian
      patient aged 51, suffering for 8 years from a strongly disabling akinetorigid
      form of PD, complicated by an on-off effect (Hoehn and Yahr stage 5 in the worst
      off motor phase). Stereotactic surgery was done on one side under local
      anesthesia. The theoretical target was chosen according to stereotactic atlases,
      based on ventriculographic landmarks such as anterior and posterior commissures
      (AC and PC). The final position of the chronic electrodes was optimized using
      electrophysiological recording and stimulation along with clinical assessment and
      surface EMG of agonist and antagonist muscles of the examined limbs. A
      spontaneous increase in neuronal activity was recorded in an area located 2-4 mm
      under the level of the intercommissural plane, 10 mm from the midline, at mid
      distance between AC and PC. Within the same place, a 130-Hz stimulation induced
      acute and reversible akinesia alleviation mainly on the contralateral limbs,
      comparable to that obtained with dopaminergic drugs. No dyskinesia, such as
      hemiballism, was induced by introduction of electrodes or by stimulation. Then a
      long-term quadripolar DBS Medtronic electrode was inserted in this area. Studies
      of the effects of chronic stimulation were extensively performed to determine the
      best spatiotemporal and electrical stimulation variables.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7631096
TI  - [What is your diagnosis? Hypertrophic cardiomyopathy].

PMID- 7631095
TI  - Subthalamotomy improves MPTP-induced parkinsonism in monkeys.
AB  - Hyperactivity of the subthalamic nucleus (STN) is major characteristic of
      parkinsonism secondary to substantia nigra lesions. Interruption of the STN
      internal pallidum (GPi) pathway is a new stereotactic target for Parkinson's
      disease. We have studied the antiparkinsonian efficacy of STN lesions in MPTP
      treated monkeys. Four rhesus monkeys were made parkinsonian by MPTP (i.v. 0.15 +/
      1 mg/kg) administration over 3 months. Unilateral subthalamotomy (kainic acid)
      was performed by a standard stereotactic method. Severity was rated from 0
      (normal) to V by fine manual motor tests. Three monkeys (severity state III/IV)
      showed marked improvement in spontaneous activity, facial expression and manual
      dexterity bilaterally but significantly greater in the limb contralateral to the
      lesion. Mild hemichorea was present in 2 and hemiballism in one. L-Dopa treatment
      (50 mg b.i.d.) enhanced the hemidyskinesias moderately. The therapeutic effect
      has persisted for over 8 months postsurgery. Monkey No.4 (severity stage V)
      showed chorea in the lower limb contralateral to the lesion but no improvement
      and died a few days later. Subthalamotomy improves parkinsonism in moderately
      severe parkinsonian monkeys. Dyskinesia might be a persistent complication.

PMID- 7631094
TI  - Neurotransmitter levels in cerebrospinal fluid in relation to severity of
      symptoms and response to medical therapy in Parkinson's disease.
AB  - Determinations of biopterin (BP), homovanilic acid (HVA), glutamic acid (GTA),
      and glutamine (GT) levels in cerebrospinal fluid (CSF) obtained through a lumbar
      tap were performed in 20 parkinsonian patients in different stages of evolution
      and without medication. In patients with motor symptoms not related to
      Parkinson's disease (dystonia, dyskinesia and essential tremor) (n = 4). In 7
      other neurological patients subjected to spinal tap for diagnostic procedures
      neurotransmitters were also determined and taken as control groups. In 14 of the
      patients with Parkinson's disease, the symptoms were evaluated using conventional
      scales (UPDS, NYPDS, NWPDS, Schwab and England, and Hoehn and Yahr scale). The
      amplitude and the frequency of tremor were quantitatively evaluated through a
      single plane accelerometer Grass SP-1, akinesia was measured through reaction
      time to auditory stimuli, and rigidity through the speed of lineal movement.
      Evaluations were performed with the patient not on any medication for 1 week and
      repeated 1 h after the intake of 250 mg of 200/50 L-dopa/carbidopa preparation
      (Sinemet) and on a different day after the intake of biperiden (Akineton) 6
      mg/day. Differences in neurotransmitter or metabolites levels between Parkinson's
      disease and control groups were determined through an independent Student's t
      test. Correlation between severity of symptoms in the scales and for each
      individual symptom measured through the quantitative tests and the levels of
      neurotransmitters in CSF were evaluated through the Pearson correlation analysis
      test. Modifications in the motor performance after administration of Sinemet and
      Akineton, and the levels of neurotransmitters were indirectly determined.
      RESULTS. (1) There were significant differences between the levels of BP and GT
      in patients with Parkinson's disease and control groups, (2) lower GTA levels
      correlated with more severe rigidity and akinesia, and with the best response to
      the administration of L-dopa and may be an important marker for prognosis, and
      (3) lower levels of GT correlated with least akinesia, but not with tremor, which
      may indicate that the akinesia depends on other biochemical abnormalities besides
      dopamine depletion.

PMID- 7631097
TI  - [Cotinine--a useful biomarker for tobacco use?].
AB  - Nicotine consumption is one of the most important avoidable risk factors for
      atherosclerosis and cardiovascular, pulmonary as well as many other diseases. In
      daily practice one cannot always clearly detect whether a patient remains really
      abstinent. 68 patients following consultations for risk factors were included in
      this study. Smoking habits were evaluated by means of a questionnaire and by
      measurement of carbon monoxide concentration in the breath; also the cotinine
      concentrations in saliva and urine were investigated during consultation.
      Cotinine is one of the most important metabolic product of nicotine. Smokers
      showed significantly increased carbon monoxide concentrations in the breath as
      well as increased cotinine concentrations in urine and saliva. Anamnestic
      information from patients about their nicotine consumption correlated well with
      the cotinine concentration in urine and saliva (r = 0.54). The best correlation
      was found between creatine-corrected cotinine concentration and cigarette
      consumption on the day preceding in measurement (p < 0.001, r = 0.66). It is not
      clear if and to what extent cotinine determination may qualify for the evaluation
      of passive smoking; however, measurement of cotinine concentrations in saliva (or
      urine) represents a good biochemical parameter for the control of nicotine
      abstinence.

PMID- 7631098
TI  - [Sigmoid volvulus--clinical, radiological and therapeutic aspects of rare
      disease].
AB  - Volvulus of the sigmoid colon is a common cause of colonic obstruction in many
      parts of the world, mainly in developing countries and in Scandinavia, but is
      rare in the Western Hemisphere, where it occurs in elderly patients who often
      have serious coexisting diseases, especially cardiovascular and neuropsychiatric
      disorders. Although many patients present with the typical triad of abdominal
      pain, distension and constipation, the disease is correctly diagnosed only in
      about 62%. Diagnostic delay is due in part to the relative rarity of the illness,
      in part to the variety of the clinical and radiologic presentation, and it might
      contribute to the high mortality. Treatment consists in endoscopic decompression,
      whenever there are no compromised intestines, followed by an elective, sigmoid
      resection in otherwise healthy patients, because the risk of recurrence is high
      after nonoperative decompression alone. Hartmann's procedure is the safest
      procedure in patients with ischemic necrosis of the sigmoid colon. The site of
      primary resection and anastomosis with viable bowel remains controversial.
      Knowledge of sigmoid volvulus is of general interest with respect to the growing
      number of elderly patients, especially those residing in nursing homes and
      psychiatric institutions.

PMID- 7631093
TI  - Long-term effects of medical and surgical treatments on Parkinson's disease.
AB  - Three groups of patients with Parkinson's disease (PD) were studied: (1) PD
      patients treated medically with L-Dopa and anticholinergics, (2) PD patients
      treated with thalamo-subthalamotomies plus medical treatment, and (3) PD patients
      treated with autologous adrenal medullary transplantation to right caudate
      nucleus plus medical treatment. Evaluations prior and 1, 6 and 12 months after
      treatment were accomplished with PD scales (NYPDS, UPDS, Schwab and England and
      Hoehn and Yahr scales). No attempt was made to compare one PD after treatment in
      each group. Statistical analysis was performed with the Friedman-Anova test.
      Group 1 did not show significant improvement at any time but deterioration at 12
      months. Group 2 showed significant improvement at 1 month but at 12 months
      deterioration occurred mainly in the mental condition and akinesia. Group 3 did
      not show significant improvement at any time but at 12 months there was a
      tendency of improvement in self-sufficiency.

PMID- 7631099
TI  - [The changing role of hospitals].
AB  - The Hospital Committee of the European Union has redefined the role of the
      hospital within a changing society. In future the hospital will be dedicated to a
      clear vision of public health and will constitute part of a network of integrated
      care. From a bed-focused enterprise it will become a health centre providing all
      services requisite for the care of acute, psychiatric and chronically ill
      patients, whether stationary, as outpatients or in daycare. This center will be
      distinguished from other care services by its operative technical resources and
      by its highly motivated and well-trained staff.

PMID- 7631101
TI  - [A case from practice (328). Chronic alcohol abuse with alcoholic polyneuropathy,
      alcoholic character change and alcoholic hepatopathy. Latent syphilis. Post
      hepatitis A status].

PMID- 7631100
TI  - [Fever of unknown origin].
AB  - A 25-year-old patient presented with fever over a period of more than three
      months, night sweats, fatigue and a weight loss of more than 10 kg. A
      splenomegaly and an enlargement of cervical, thoracic and abdominal lymph nodes
      were found. The suspected malignant hematologic disorder could not be confirmed.
      Instead, epithelioid noncaseating granulomas in the bone marrow and a cervical
      lymph node as well as an elevated serum ACE and a lymphocytic alveolitis were
      found. These findings led us to the conclusion that the patient was suffering
      from sarcoidosis. Treatment with corticosteroids resulted in complete regression
      of all symptoms, including the splenomegaly and the enlargement of the lymph
      nodes. Sarcoidosis is an important consideration in differential diagnosis of
      fever of unknown origin, even in the absence of pathological changes on X-ray
      films of the chest.

PMID- 7631103
TI  - [Dying: Taboos, fears, denials...].

PMID- 7631102
TI  - [Preventive actions. A study in basic health areas].

PMID- 7631107
TI  - ["Discussion group": pedagogical instrument to deepen acquired knowledge].

PMID- 7631106
TI  - [Organizers and founders of the Association of Community Nursing. Shouldering
      care compromises].

PMID- 7631105
TI  - [Nursing publications in Asturia].

PMID- 7631104
TI  - [Papillomavirus infection. A study of incidence].

PMID- 7631108
TI  - [Community nursing. Repercussions on health centers].

PMID- 7631109
TI  - [Publicity, health and health education].

PMID- 7631110
TI  - [Stress in nursing professionals. On what and on whom does it reflect?].

PMID- 7631111
TI  - [Sanitary refuse. New regulations].

PMID- 7631112
TI  - [Service contract in primary care].

PMID- 7631113
TI  - [House call. Medical diagnosis and nursing diagnosis].

PMID- 7631114
TI  - [Child nutrition and vitamin D].

PMID- 7631115
TI  - [Patients and the quality of life. Development since the introduction of
      intensive care units].

PMID- 7631116
TI  - [The social advances on our continent are meaningful in the whole world.
      Interview by Angels Elias].

PMID- 7631117
TI  - [Case management. Development of a new organizational model].

PMID- 7631118
TI  - [Informal care].

PMID- 7631119
TI  - [Catastrophe planning].

PMID- 7631120
TI  - [Patient education. Pedagogy for the horse that is not thirsty].

PMID- 7631121
TI  - Restriction endonuclease cleavage analysis of herpes simplex virus type 2 from
      Chiang Mai, Thailand and Okinawa, Japan.
AB  - Genomic variations of herpes simplex viruses type 2 (HSV 2) isolated from Chiang
      Mai, Thailand and Okinawa, southernmost part of Japan were studied. The genomic
      polymorphism of 40 HSV 2 Chiang Mai strains and 10 HSV 2 Okinawan strains was
      analyzed by means of the variations of cleavage sites and electrophoretic
      mobilities of DNA fragments after digestion with 4 restriction endonucleases (RE
      (BamH I, Kpn I, EcoR I, and Bgl II)). Using the main 6 variable RE cleavage
      sites, HSV 2 strains were classified into 10 major groups. The strains
      categorized into group 1 and 9 were predominant in Chiang Mai. Groups 1, 3, 4, 5,
      6 and 7 were found only in Chiang Mai, but contained only a few strains each.
      Groups 2 and 10 were found only in Okinawa, whereas groups 8 and 9 were found in
      both Chiang Mai and Okinawa.

PMID- 7631122
TI  - Prevalence, geographical distribution and clinical manifestations of
      onchocerciasis on the Island of Bioko (Equatorial Guinea).
AB  - A survey for the prevalence, geographical distribution and clinical
      manifestations of onchocerciasis was conducted on the Island of Bioko (formerly
      Fernando Poo), Equatorial Guinea, between 1987-89. The whole population (1799
      inhabitants) of thirteen villages distributed around the island was surveyed.
      Identification data, physical examination and Snellen "E" test for visual acuity
      were performed. Skin snips were taken from both iliac crests and right scapula
      and calf. Differential diagnosis between Onchocerca volvulus and Mansonella
      streptocerca was carried out in both fresh and Giemsa stained preparations. The
      overall prevalence (+ skin snips) and mean microfilarial density were 75.2%
      (range 51.9% to 87.1%) and 32.2 mf/snip respectively. Skin snips showed a higher
      microfilarial density from iliac crests. The following clinical manifestations
      were found: 560 (31.2%) with nodules; 518 (28.8%) with dermatitis, pigmentation
      changes and cutaneous atrophy; 753 (41.9%) with lymphoadenopathy and lymphoedema.
      Blindness due to different causes was registered in 13 cases (0.8%). The results
      showed that onchocerciasis is hyperendemic and widespread over the island. It is
      estimated that almost the whole population (62,000) is at risk of infection.

PMID- 7631123
TI  - The chemotherapy of onchocerciasis XVIII. Aspects of treatment with suramin.
AB  - We report the clinical and parasitological effects of a modified treatment
      regimen for suramin. Twenty adult males received up to 5 g (72.5 to 84.7 mg/kg)
      of suramin over 36 days. Detailed clinical and laboratory examinations were done
      before treatment and then at intervals over 2 years. Nodules were removed at 6,
      13, 26 and 52 weeks for histology. Systemic tolerance was good. Anterior segment
      inflammation was however common and 2 patients required intervention to prevent
      posterior synechiae. No new posterior segment lesions developed; a rare
      improvement occurred in one patient with papillitis. Proteinuria, mostly mild,
      occurred in nearly all patients. Previously unreported renal glycosuria was
      documented in one patient. Microfilariae in the skin and anterior chamber did not
      change significantly for 5 or more weeks after which rapid reductions occurred.
      Ocular parasites were absent at 2 years and skin microfilariae were near zero.
      Peripheral blood eosinophil counts fell in parallel with those of microfilariae
      in the skin and anterior chamber and were normal at one and two years. These
      findings at 2 years may provide indirect evidence of a macrofilaricidal or a
      permanent chemosterilant effect on the adult worms. Nodule examination revealed
      an embryotoxic effect from week 6, a lethal effect on the male worms from month 3
      and on the female worms from month 6 after treatment started. At one year 34% of
      the female worms examined were alive. Thus total doses of suramin in the range
      72.5 to 84.7 mg/kg have only a modest lethal effect on the female worms. Suramin
      remains a restricted drug and a suitable replacement is urgently needed.

PMID- 7631125
TI  - Evaluation of suramin, ivermectin and CGP 20376 in a new macrofilaricidal drug
      screen, Onchocerca ochengi in African cattle.
AB  - To aid the development of a macrofilaricidal agent for Onchocerca volvulus, the
      African bovine parasite, O. ochengi, was evaluated as a drug screen by testing
      three known filaricidal drugs. Groups of five Zebu cattle, naturally infected
      with more than 15 palpable O. ochengi nodules in the ventral skin, were treated
      with either suramin (10 mg/kg/day i.v. for 6 days), ivermectin (200
      micrograms/kg, s.c.), CGP 20376 (20 mg/kg orally) or left untreated as controls
      and examined at intervals up to 137 days post-treatment (d.p.t.). After
      ivermectin treatment, microfilarial densities in the skin decreased within one
      week to virtually zero and remained at a very low level. A similar rapid and
      profound reduction was seen after CGP 20376 treatment, but by 137 d.p.t.
      microfilarial skin densities were approaching pre-treatment levels. With suramin,
      skin microfilarial densities fell to very low levels after 12 weeks but rose
      slightly by 137 d.p.t. Effects on the macrofilariae were assessed by sequential
      nodulectomies at -3 and 28, 84 and 137 d.p.t. By 137 d.p.t. embryogenesis was
      almost completely interrupted in the CGP 20376 and ivermectin treated animals,
      although not in the suramin treated group, but in all three groups the majority
      of remaining intrauterine microfilariae were pathologically altered. Degenerating
      intrauterine microfilariae accumulated in the ivermectin and in the CGP 20376,
      but not in the suramin treated worms. The motility of male and female worms was
      not reduced by any treatment except for female worms at 84 d.p.t. with CGP 20376.
      Viability of the worms as indicated by the MTT-formazan reduction assay was not
      reduced in any of the treatment groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7631124
TI  - Facilitation in Anopheles and spontaneous disappearance of filariasis: has the
      concept been verified with sufficient evidence?
AB  - The validity of recently much argued phenomenon of facilitation in the
      transmission of filariasis was considered by examining previously published
      papers. It was concluded that there was no clear evidence to support the
      existence of facilitation and facilitation-based unstable equilibrium in relation
      to microfilaria prevalence and density in human population below which filariasis
      would spontaneously disappear, even when the vector was Anopheles mosquitoes.
      Instead, the existence of a critical level of man/mosquito contacts for the
      disappearance of filariasis was suggested.

PMID- 7631126
TI  - Quinine resistant falciparum malaria acquired in east Africa.
AB  - A 43 year old man with falciparum malaria acquired in East Africa was treated
      with quinine intravenously at a loading dose of 500 mg and subsequently 500 mg
      tid. Within 42 hours after initiation of treatment the parasitaemia increased
      from 2% to 16%. A RIII-resistance against quinine was suspected and therapy was
      switched to oral administration of halofantrine (500 mg at 6 hourly intervals)
      which led to complete recovery. Blood samples were cultured for malaria parasites
      42 hours after start of therapy with quinine but before initiation of therapy
      with halofantrine. In vitro resistance testing was performed with samples
      directly derived from the patient and after 24 and 48 hours of culturing. In
      repeated tests an in vitro resistance to quinine could be confirmed (IC50: 25.6 x
      10(-6) mol/l, IC99: > 51.2 x 10(-6) mol/l) while the strain was fully susceptible
      to chloroquine (IC50: < 0.4 x 10(-6) mol/l, IC99: 1.6 x 10(-6) mol/l), mefloquine
      (IC50: < 0.4 x 10(-6) mol/l, IC99: 3.2 x 10(-6) mol/l), tetracycline (IC50: 0.16
      x 10(-6) mol/l, IC99: 0.32 x 10(-6) mol/l) and halofantrine (IC50: 0.02 x 10(-6)
      mol/l, IC99: 0.04 x 10(-6) mol/l). Increased susceptibility to quinine after
      addition of verapamil was noted. The presence of a specific mutation, on the
      pfmdr1-gene on chromosome 5, previously associated with chloroquine drug
      resistance, could be confirmed by polymerase chain reaction. To our knowledge a R
      III-in vivo and in vitro resistance of Plasmodium falciparum to quinine has not
      been described yet in East Africa.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7631127
TI  - Trypanosoma brucei brucei: antitrypanosomal evaluation of stilbamidinium
      hexachloroiridiate on the murine CNS model and iridium serum kinetics in infected
      sheep.
AB  - Stilbamidinium hexachloroiridiate was found trypanocidal in vitro against
      Trypanosoma brucei brucei IPP at 600 microM after a 1 h incubation period and 30
      microM after 24 h. This activity was confirmed in mice with a subcutaneous
      treatment at 20 mg/kg in a single dose. It was then evaluated on T.b. brucei
      murine CNS model. At the early stage, a subcutaneous treatment at 2 mg/kg/day x 5
      cured 50% mice where-as one single dose at 10 mg/kg was completely inactive.
      Higher doses failed to cure the mice. Nevertheless, hexachloroiridiate salt of
      stilbamidine was 3.3 fold less toxic than dihydrochloride salt. Although the
      compound appeared inactive at the late stage of the murine trypanosomiasis, the
      difference of toxicity justified its evaluation on the early stage of sheep
      trypanosomiasis. The compound was trypanocidal at 2 mg/kg in a single dose when
      administered 8 days after infection. The study of iridium serum kinetic showed
      that stilbamidinium hexachloroiridiate was distributed rapidly according to a
      monocompartmental model. Moreover, iridium persisted in serum for a long time.
      The compound in aqueous suspension with 1% carboxymethylcellulose acted therefore
      as a controlled release system with a bioavailability allowing its trypanocidal
      action at the early stage.

PMID- 7631128
TI  - A novel in vitro screening assay for trypanocidal activity using the fluorescent
      dye BCECF-AM.
AB  - A cell viability assay, using fluorescence measurements has been developed for
      the screening of new compounds against African trypanosomes. 2',7'-Bis
      (carboxyethyl)-5(6)-carboxyfluorescein-pentaacetoxymethyles ter (BCECF-AM), an
      esterase substrate, was used in the assay as a marker for cell viability.
      Fluorescence was quantified using an automated fluorescence scanner for multi
      well plates. Trypanosoma brucei rhodesiense, T. congolense, T. evansi and T.
      equiperdum from continuously growing cultures were exposed to various
      concentrations of trypanocidal drugs for an incubation period of 72 h at 37
      degrees C. Then BCECF-AM was added to the cell suspensions and after 60 minutes
      the fluorescence of the trypanosome suspension was measured using the Millipore
      Cytofluor 2300 fluorescence scanner, at 485 nm excitation and 530 nm emission
      wavelengths. Results of kinetic studies of the hydrolysis of the non-fluorescent
      BCECF-AM in trypanosomes showed that BCECF-AM is readily cleaved by non-specific
      esterases to a highly fluorescent product. Drug concentrations causing 50%
      inhibition of fluorescence (IC50-values) were measured fluorimetrically. Minimum
      inhibitory concentration (MIC) was determined microscopically.

PMID- 7631129
TI  - Activity and structure relationship of acridine derivatives against African
      trypanosomes.
AB  - 48 newly synthesized acridine derivatives of different classes were screened for
      antitrypanosomal activity. They showed a dose dependent effect on Trypanosoma
      rhodesiense and T. brucei bloodstream forms measured by the inhibition of
      esterase activity in a fluorescence based in vitro assay. After analysis of the
      IC50 and MIC values of the investigated acridines it was obvious that no new
      compound reached the level of the trypanocidal drugs in use (50 ng/ml). Most of
      the derivatives had IC50 values in the range of 1 to 10 micrograms/ml. 9
      derivatives from different classes of acridines were in vitro active below 1
      microgram/ml. Correlations between structure and effect on trypanosomes have been
      elucidated by comparing the IC50 and MIC values of these compounds, in the course
      of which no significant differences in the drug susceptibility between T. brucei
      und T. rhodesiense was noticed. The dialkylaminoalkyl derivatives among the group
      of the 9-thioacridines were slightly more potent than the mono-alkylated ones.
      1,2,3,4-tetrahydro-9-thioacridines showed the influence of higher substituted
      side chains on the trypanocidal activity in the same way as 9-thioacridines. The
      corresponding ketones of 9-thioacridines confirmed the tendency of increasing
      toxicity due to the derivatisation of the dialkylaminoalkyl side chain. Within
      the series of the 9-aminoacridines the elongation of the side chain did not
      markedly change the activity, however the IC50 values are generally low between
      0.13 and 1.2 micrograms/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7631131
TI  - Chemotherapeutic effect of CGI 18041 against subperiodic Brugia malayi infection
      in Presbytis cristata.
AB  - CGI 18041, an adduct of benzothiazol isothiocyanate N-methyl piperazine, was
      evaluated for its antifilarial properties in subperiodic Brugia malayi infected
      Presbytis cristata. Animals experimentally infected with 200-400 subperiodic
      Brugia malayi infective larvae, were matched according to microfilaria density,
      infective dose, and duration of infection. They were then randomly assigned to
      various treatment and control groups. The compound was suspended in 1% Tween 20
      in distilled water, sonicated, and then fed to monkeys using a stomach tube.
      Control animals received an equivalent volume of drug diluent. CGI 18041 at a
      single oral dose of 50 mg/kg had complete adulticidal and microfilaricidal
      activities against subperiodic B. malayi in P. cristata. It was also extremely
      effective at a single dose of 25 mg/kg, the final geometric mean microfilaria
      count being 1.6% of initial level, and only 1.0% of the infective dose was
      recovered as live adult worms at autopsy 6 weeks post-treatment. In control
      animals, these were 226.9% and 5.56% respectively.

PMID- 7631130
TI  - The economic costs of illness for rural households in Burkina Faso.
AB  - Analyses of the health costs in developing countries have mainly dealt with
      provider costs. This is in spite of the fact that the bulk of illness related
      costs is borne by households. Where studied, household time and financial costs
      have not been treated in a comprehensive way. However, an incomplete cost
      assessment will lead to an underestimation of household costs. Using data from a
      household interview survey in a rural area of Burkina Faso, the authors carried
      out an exhaustive assessment of the economic cost of illness that households
      incur. Financial costs included out-of-pocket expenditures for drugs, fees,
      transport to the treatment site, lodging and food for accompanying household
      members. Time costs, in turn, were comprised of production foregone both by the
      sick person and by healthy household members, who tended to the sick. Time costs
      amounted to by far the largest proportion (73%) of total household costs. Of the
      total amount of illness related time loss of the average household, 45% was due
      to the fact that healthy household members tended to or accompanied their sick
      kin. Of the financial cost items, expenditures for drugs or traditional products
      represented 62%. When Western type services were sought, expenditures for
      transport, food etc., exceeded those for treatment fees. Total cost of illness
      was 4,002 F CFA/month for the average household. This amounted to 3.7% of
      household income and to 6.2% of household expenditures in the reference month.
      The authors discuss policy measures aimed to reduce household time
      costs.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7631133
TI  - Female preponderance for development of arthritis in rats is influenced by both
      sex chromosomes and sex steroids.
AB  - Autoimmune arthritis was induced after a single injection of the non-immunogenic
      adjuvant (avridine) or with autologous rat type II collagen. Females of two
      different rat strains, DA and LEW, were found to be more susceptible than males.
      To investigate further the mechanisms behind the female preponderance, we
      selected the avridine induced arthritis model. This is known to be a chronic
      joint-specific disease which is T-cell dependent and associated with MHC genes
      and, therefore, is an appropriate model for rheumatoid arthritis. To address the
      possibility of sex chromosome involvement, reciprocal F1 hybrids were produced.
      Female (DAxLEW)F1 rats were found to be more prone to arthritis than their male
      counterparts. This difference could be explained, at least partly, by the
      influence of sex chromosomes since reciprocal (LEWxDA)F1 rats showed no sex
      linkage. However, the sex linkage was more pronounced in normal rats when
      compared to castrated (DAxLEW)F1 rats indicating a role for sex hormones in
      conjunction with the sex chromosome-linked effect. Both oestrogen and
      testosterone had a suppressive effect on the development of arthritis. The
      findings presented here suggest the presence of a sex chromosome gene, which
      mediates its function only in the presence of sex hormones and is associated with
      a female preponderance for development of arthritis.

PMID- 7631132
TI  - Combination ivermectin plus diethylcarbamazine, a new effective tool for control
      of lymphatic filariasis.
AB  - In 1993, a three arm double-blind controlled trial was implemented in French
      Polynesia, to compare the tolerance and efficacy of single doses of the
      combination ivermectin (IVR) 400 micrograms.kg-1 plus diethylcarbamazine (DEC)
      6mg.kg-1 vs IVR 400 micrograms.kg-1 or DEC 6 mg.kg-1 alone, for treatment of
      Wuchereria bancrofti carriers. Of the 57 treated male patients in whom
      microfilaremia (mf) densities ranged from 22 to 4,709 mf/ml, three groups of 19
      were randomly selected, and allocated to one of the three treatments. Twelve
      months after treatment 37%, 16% and 16% of patients were mf negative in groups
      DEC, IVR and IVR plus DEC respectively. Mf percent return to pretreatment level
      was significantly lower in the group IVR + DEC (1.9%) than for DEC 6 (14.7%) or
      IVR 400 (11.6%). Antigenemia percent return to pretreatment level was lower in
      the groups IVR + DEC or DEC 6 than for IVR 400. The combination IVR + DEC proved
      to be the most effective on macrofilariae and microfilariae (antigenemia and mf
      negative patients). The combination will be a very powerful tool for control of
      lymphatic filariasis. An annual filariasis day could be the most cost-effective
      strategy for administration of the drugs.

PMID- 7631134
TI  - TNF-alpha dominates cytokine mRNA expression in lymphoid tissues of rats
      developing collagen- and oil-induced arthritis.
AB  - Experimental arthritis can be induced in the DA rat strain with rat type II
      collagen (RCII) administered in Freund's incomplete adjuvant oil (FIA) or with
      only FIA. If ovalbumin (Ova), is added to these arthritogens the development of
      arthritis is blocked. To investigate the mechanisms responsible for induction of
      arthritis, as well as inhibition of arthritis, a kinetic study of the local
      cytokine expression in lymph nodes has been performed after immunization with the
      above mentioned agents. By using in situ hybridization techniques, mRNA
      expression of TNF-alpha, IL-2, IFN-gamma and IL-4 was determined. The results
      show a rapid and pronounced accumulation of TNF-alpha mRNA expression, in
      RCII/FIA and FIA immunized rats. This pronounced expression of TNF-alpha mRNA was
      not recorded in the Ova/FIA immunized animals, which instead were the only
      animals in which the IL-4 gene was expressed. The expression of IFN-gamma mRNA
      was limited in RCII/FIA- and FIA-immunized rats, whereas IL-2 mRNA expression was
      detected only after RCII/FIA injection. Lymph node cells from RCII-immunized
      animals generated a high amount of TNF-alpha mRNA after restimulation with RCII,
      whereas restimulation with the mitogen Con A generated a cytokine mRNA response
      dominated by IL-2 and IFN-gamma. These and other results indicate that a strong
      local expression of TNF-alpha, induced by arthritogenic stimuli, may be important
      for the induction of arthritis. Moreover, the elicitation of an immune reaction
      against Ova, may inhibit arthritis development by contributing to a shift in the
      initial arthritogenic cytokine response.

PMID- 7631135
TI  - No evidence for TCR V beta repertoire changes influencing disease protection in E
      transgenic NOD mice.
AB  - In order to study whether positive selection of T cells plays any role in the MHC
      dependent protection from diabetes in the non-obese-diabetic (NOD) mouse, the T
      cell V beta repertoire has been studied in NOD mice and in NOD mice either
      transgenic for the wildtype MHC class II E alpha gene, or for delta Y, a promotor
      mutagenized E alpha gene with a restricted tissue expression. The E alpha
      transgenic line is protected from both insulitis and diabetes. The delta Y
      transgenic line is neither protected from insulitis nor from diabetes, although
      it can perform both positive and negative E-mediated selection in the thymus. The
      V beta repertoire was studied in the pancreatic lymph nodes as these drain the
      area which is the target for the autoimmune attack. We see no evidence for E
      alpha TCR V beta repertoire differing from both nontransgenic NOD mice and delta
      Y mice despite its striking difference in susceptibility to autoimmunity. We
      conclude that none of the differences in the TCR V beta repertoire of E alpha
      transgenic NOD mice hitherto observed are likely to explain the protective effect
      of E molecule expression in NOD mice.

PMID- 7631136
TI  - ADCC-mediating capacity in children with cow's milk protein intolerance in
      relation to IgG subclass profile of serum antibodies to beta-lactoglobulin.
AB  - In a previous study sera from children with cow's milk protein intolerance (CMPI)
      exhibiting gastrointestinal symptoms were found to efficiently induce antibody
      dependent cell-mediated cytotoxicity (ADCC) to beta-lactoglobulin-coated cells.
      In contrast, sera from children with coeliac disease showed a low ADCC-mediating
      capacity, despite high levels of IgG anti-beta-lactoglobulin antibodies. The
      study described here was undertaken to evaluate whether differences in IgG
      subclass profile of anti-beta-lactoglobulin antibodies could explain the observed
      variations in the ADCC-mediating capacity. Forty-eight sera from the following
      groups of children were investigated: CMPI with predominantly gastrointestinal
      symptoms, CMPI with skin symptoms of immediate-onset, children with untreated
      coeliac disease and healthy references. Absorption experiments indicated that
      primarily IgG1 antibodies were responsible for the ADCC-mediating capacity of the
      sera. Accordingly, the ADCC reactivity of individual sera correlated with their
      IgG1 antibody levels. Sera from CMPI children with gastrointestinal symptoms,
      most of which had a high ADCC reactivity, also demonstrated a distinctive
      subclass pattern of their anti-beta-lactoglobulin antibodies with higher relative
      proportions of IgG1 (ratios: IgG1/IgG, IgG1/IgG3 and IgG1/IgG4) than those from
      the other diagnostic groups. Using logistic regression analysis, the diagnostic
      potential of ADCC as well as of different IgG subclass variables for the
      recognition of gastrointestinal symptoms caused by CMPI was evaluated. The ADCC
      reactivity of sera was found to be the best predictor in this model.

PMID- 7631137
TI  - Monozygotic rheumatoid arthritis twin pairs express similar levels of conserved
      immunoglobulin V gene in polyclonal rheumatoid factors irrespective of disease
      status.
AB  - The degree of polyclonal RF heterogeneity was assessed in diseased and non
      diseased twins with rheumatoid arthritis (RA). The distribution of variable
      region determinants encoded by a set of immunoglobulin germline, or minimally
      mutated germline, genes within IgM RF, IgG RF and IgA RF isotypes was determined
      by ELISA using specific mouse monoclonal antibodies (MoAb) in fractionated plasma
      from 12 members of six monozygotic twin pairs with RA. The results reveal that at
      least 40% (range approximately 18-87%) of IgM RF are encoded by a small set of
      approximately 10 genes from the VH1, 3 and 4 families. Furthermore, a significant
      proportion of IgG RF and IgA RF (approximately 30%) are also encoded by these
      same genes. Comparison with RF-negative fractions of immunoglobulins showed that
      the examined variable region determinants were overrepresented in the RF
      fractions. The level of expression of the variable region determinants in RF were
      generally similar within twins but different between unrelated twin pairs
      irrespective of disease status. The variability of VH gene usage between
      unrelated individuals suggests that the level of expression and regulation of the
      variable region determinants may be genetically regulated or influenced by common
      environmental factors.

PMID- 7631138
TI  - TNF inhibitors are produced spontaneously by rheumatoid and osteoarthritic
      synovial joint cell cultures: evidence of feedback control of TNF action.
AB  - We have proposed the hypothesis that tumour necrosis factor alpha (TNF-alpha) has
      a pivotal role in the pathogenesis of rheumatoid arthritis, based on in vitro
      observations that in RA synovial joint cell cultures removal of TNF-alpha,
      inhibited other potentially pathogenic cytokines such as the equally
      proinflammatory cytokine interleukin 1 (IL-1) and the macrophage activating
      factor, GM-CSF. Here we describe that in both rheumatoid (RA) and osteoarthritic
      (OA) synovial cultures there is a homeostatic mechanism to regulate the
      activities of TNF-alpha. This concept is based on several observations. First in
      these synovial joint cell cultures the substantial discrepancy between the levels
      of bioactive and immunoreactive TNF-alpha indicates the presence of an inhibitor.
      Second, TNF binding proteins are produced spontaneously, which are the soluble
      variants of surface p75 and p55 TNF receptor. The amount of soluble TNF receptors
      (sTNF-R) produced varied between cultures; p75 sTNF-R was more abundant than p55
      sTNF-R (as detected by ELISA), and both were produced at higher levels by RA
      synovial joint cells in culture, compared to OA cultures. These TNF binding
      proteins act as endogenous inhibitors of TNF-alpha, since blocking their activity
      in synovial joint cell culture supernatants with MoAb to p55 and p75 sTNF-R
      enhanced their cytotoxic activity in the TNF bioassay. The regulation of
      production of these sTNF-R in synovial joint cell cultures is important as the
      balance between TNF-alpha and sTNF-R production may determine the outcome of the
      inflammatory process.

PMID- 7631139
TI  - Enhancement of interleukin-6 production by fibrinogen degradation product D in
      human peripheral monocytes and perfused murine liver.
AB  - The effect of fibrinogen degradation products D and E (FDP-D, FDP-E) on IL-6
      production in perfused mouse livers and peripheral monocytes is studied.
      Similarly to bacterial endotoxin FDP-D is highly potent to augment the IL-6
      production measured in perfused mouse livers, while FDP-E is not stimulatory. FDP
      D but not FDP-E is able to stimulate the in vitro IL-6 production of human
      peripheral monocytes, as well. Plasmin alone is almost ineffective on IL-6
      production both in perfused livers and monocytes. Our findings suggest a direct
      positive feedback circuit, among fibrinogen, FDP and IL-6.

PMID- 7631140
TI  - Stimulation by T cell independent antigens can relieve the arrest of
      differentiation of immature auto-reactive B cells in the bone marrow.
AB  - The pair of microH-chain and kappa L-chain transgenes encoding the Sp6 TNP/DNA
      specific IgM was bred onto the rearrangement-deficient genetic background of RAG
      2T mice, and onto the kappa L-chain expression-deficient background of iE kappa T
      mice. Bone marrow of Sp6 transgenic RAG-2T mice contained normal numbers of
      B220(CD45R)+c-kit+ pro/preB-I-like cells and normal numbers of B220(CD45R)+TAC+
      preB-II-like cells. Most strikingly, the numbers of immature sIgM+ B cells in the
      bone marrow were at least five-fold lower than normal, while mature B cells were
      almost undetectable in bone marrow as well as spleen. Hence, B cell development
      in these mice appears to be arrested at the transition from preB-II to immature B
      cells. The contents of bone marrow and spleen of the different precursors,
      immature and mature B cell compartments in Sp6iE kappa T mice were found to be
      similar to those of normal mice except that all sIg+ cells expressed lambda L
      chains, of which 40% coexpressed the transgenic kappa L-chain. It indicates that
      the repertoire of lambda L-chain rearrangements and the lambda L-chains expressed
      from it suffices to relieve the arrest of differentiation seen in Sp6RAG-2T mice.
      The T cell-independent antigen TNP-Ficoll elicited within 5 days a response of
      the Sp6RAG-2T mice to develop to IgM-secreting cells and to fill the serum pool
      with the Sp6 transgenic IgM to 100 micrograms/ml, i.e. to normal serum levels of
      IgM in normal mice. TNP-Ficoll appears to interfere with the arrest of
      differentiation. Two scenarios for this arrest of differentiation and its relief
      by the T-independent antigen TNP-Ficoll are discussed.

PMID- 7631141
TI  - The network theory: 21 years later.
AB  - The network theory was proposed 21 years ago, attracting then much interest as
      applied to the regulation of (clonal) immune responses. The first 10 years of
      'idiotypic network' research have thus addressed questions that were already
      appropriately solved by the clonal selection theory, leading to a justifiable
      loss of its impact. In contrast, 'second generation networks', concentrate on
      systemic properties that emerge from a network organization, thus providing a
      framework for several major questions that seem to supersede clonal solutions:
      the developmental 'learning' of self antigenic composition and the maintenance of
      the respective 'memory' (self-tolerance), repertoire selection and the
      homeostatic regulation of lymphocyte numbers, natural immune activities that are
      independent of external antigens, the physiology of autoreactivity. The immune
      network may well contribute solutions to autoimmune diseases, where clonal
      approaches, classical and modern alike, have failed.

PMID- 7631142
TI  - Engagement of MHC class I proteins on natural killer cells inhibits their killing
      capacity.
AB  - We have studied whether engagement of MHC class I (MHC-I) molecules on natural
      killer (NK) cells can influence the NK killing activity. Human NK effector cells,
      enriched by nylon wool passage, were incubated with monoclonal antibodies (MoAb)
      to MHC-I followed by cross-linking with secondary rabbit anti mouse Ig or
      streptavidin. Cross linking of MHC-I molecules on NK cells resulted in a clear
      inhibition of the NK activity against the target cells K562, Molt-4 and U937. The
      inhibitory effect was selective for MHC-I and was not seen with MoAb to MHC-II or
      CD56 molecules. The inhibition was not mediated via Fc receptors since F(ab)2
      fragments of the MHC-I MoAb W6/32 were as effective as the intact antibody. The
      best inhibition of NK activity was obtained using biotin-labelled F(ab)2
      fragments of W6/32 and streptavidin as a cross-linker, where up to 70% reduction
      in NK cell activity was observed. Antibody dependent cellular cytotoxicity (ADCC)
      was also inhibited by cross-linking MHC-I molecules on the effector cells. The
      results show that antibody mediated cross-linking of MHC-I proteins on NK cells
      can inhibit their killing capacity. This indicates that MHC-I molecules on NK
      cells can be involved in the regulation of NK cytotoxicity, perhaps by
      transmitting inhibitory signals into the NK cell.

PMID- 7631143
TI  - Comparison of the number of IL-4 and IFN-gamma secreting cells in response to the
      malaria vaccine candidate antigen Pf155/RESA in two groups of naturally primed
      individuals living in a malaria endemic area in Burkina Faso.
AB  - The enzyme-linked immunospot (ELISPOT) assay was used to enumerate the number of
      IFN-gamma and IL-4 producing cells after in vitro stimulation with a highly
      purified recombinant malaria vaccine candidate antigen (r-Pf155/RESA) or
      synthetic peptides corresponding to its major T-cell epitopes. Two groups of
      naturally primed individuals living in rural areas of Burkina Faso were studied.
      The donors comprised one group of healthy (non-parasitemic) mainly adult people
      and one parasitemic mainly younger people. IL-4 producing cells were detected in
      response to PHA but no such cells were detected in response to the malarial
      antigens. The most frequent IFN-gamma responses were seen with r-Pf155/RESA.
      Thus, after stimulation with this antigen 52% of the donors responded positively
      in the ELISPOT assay, while only 17% responded to the synthetic peptides,
      suggesting that the rPf155/RESA contained T-cell epitopes not covered by the
      peptides used in this study. The number of IFN-gamma producing cells in response
      to the malarial antigens did not differ between the two groups. However, IFN
      gamma levels found in sera from the parasitemic individuals were significantly
      higher than in those from healthy donors. This latter finding and the lack of
      differences seen in the number of IFN-gamma producing spots in the two groups
      indicate that IFN-gamma producing cells may have sequestered to other organs in
      the parasitemic group.

PMID- 7631144
TI  - Homology between the MPB70 and MPB83 proteins of Mycobacterium bovis BCG.
AB  - Isolation of MPB83 from Mycobacterium bovis BCG Tokyo culture fluid is described.
      MPB70 and MPB83 have similar molecular mass as judged by SDS-PAGE but differ in
      isoelectric points. Peptides isolated after CNBr cleavage of MPB83 revealed
      extensive homology as well as distinct differences from corresponding parts of
      the amino acid sequence deduced from the mpb70 gene cloned by Terasaka et al.
      Antibodies produced by immunization with MPB70 and MPB83 had distinctly different
      fine specificity revealing cross-reactivity between the proteins. These findings
      indicate that two distinct, homologous genes code for these proteins.
      Sensitization with live BCG Tokyo also induced T cell responses to MPB83 with
      development of delayed type hypersensitivity in guinea pigs.

PMID- 7631145
TI  - The somatic hypermutation activity of a follicular lymphoma links to large
      insertions and deletions of immunoglobulin genes.
AB  - A biopsy specimen from a patient with follicular lymphoma was divided into two
      fragments. DNA was extracted from one fragment and a 1.2 kb region of the
      functional heavy chain (IgH) gene was amplified, cloned and sequenced (eight
      clones). From the other fragment a cell line (HF-1) was started. The IgH gene
      region was amplified from the cell line, and sequenced without cloning. The nine
      sequences obtained could be arranged into a genealogical tree where the
      individual sequences differed from the deduced ancestor by 16-29 single
      nucleotide changes, some also by an insertion and/or a deletion. It is apparent
      that the sequence alterations were caused by somatic mutations during the growth
      of the lymphoma. The comparison of the sequences with two published (allelic)
      germline sequences of the human JH region showed approximately 20% non-homology.
      The differences included five additional multinucleotide insertion/deletion
      changes, the longest of them a 101-nucleotide insertion. Two long insertions were
      homologous to the adjacent germline sequences. We propose that most of the
      changes observed, including long deletions and insertions, represent or are
      linked to somatic hypermutation events of the Ig gene type. Although in a few
      cases large deletions and insertions (> 2 bp) have been found in mutated
      immunoglobulin genes, our results, for the first time, firmly link these
      deletions/insertions to somatic hypermutations; their frequency was found to be
      2.2% of the observed mutational events in the non-translated gene regions. HF-1
      is the first follicular lymphoma line successfully established from a lymphoma
      known to have hypermutated its Ig genes during the malignant growth. It is a
      candidate cell line to be studied for its ability to generate mutations of B cell
      type in cell cultures.

PMID- 7631146
TI  - Relationship between the reactivity to hepatitis B virus vaccination and the
      frequency of MHC class I, II and III alleles in haemodialysis patients.
AB  - To study the immunoreactivity genes in a heterogeneous human population needs a
      large number of individuals. Associations between HLA antigens and immunoresponse
      to viral or bacterial antigens have been studied with controversial results. As a
      homogeneous population, the MHC class I, II and III allele distribution was
      studied in 153 end-stage renal disease patients (ESRD, average duration of renal
      replacement: 8.2 + 5.1 years) immunized with a recombinant hepatitis B vaccine in
      accordance to the standard vaccination schedule. Thirty-four patients with an
      antibody titre of less than 10 U/l following the last booster injection were
      considered as non-responders while 119 patients with antibody titre equal to or
      more than 10 U/l were considered as responders. The responder group was divided
      into two subgroups: low responders (antibody titre: < or = 1000 U/l) and high
      responders (antibody titre: > 1000 U/1). Marked differences were observed between
      responders and non-responders in the occurrence of carriers of different MHC
      class I, II and III alleles. Homozygotes for HLA-A1, HLA-B8, HLA-DR3 and HLA-DQ2
      were found almost exclusively in the non-responder group and significantly more
      heterozygotes for these alleles were found in the non-responder group compared to
      the responders. Similar albeit less marked differences were found in the
      frequency of some MHC class III alleles (C4A*6, C4A*QO, Bf*F, Bf*S0.7). Within
      the responder group, carriers of HLA-A2, HLA-B7 and HLA-DR4 were found to be
      clustered in the low responder sub-group whereas carriers of HLA-A1, HLA-B27, HLA
      Cw2, C4A*6 and Bf*F were observed more frequently in the group of high
      responders. Similar differences were found with extended haplotypes as well. For
      example, the extended haplotypes HLA-A1, B8, BfS, C4AQO, C4B1, DR3, DQ2 and HLA
      A1, B8, BfF, C4A6, C4B2, DR3, DQ2 were present in nine of 34 cases of non
      responders but only in one of 119 case of responders (P < 0.000001). These
      observations indicate that the presence or absence of certain MHC alleles even in
      heterozygous form determine the responsiveness to hepatitis B vaccination in end
      stage renal disease patients, and among responders, the intensity of antibody
      response is also markedly influence by immunogenetic factors.

PMID- 7631148
TI  - Constitutive and inducible cytokine mRNA expression in the human mast cell line
      HMC-1.
AB  - The discovery that mast cells are a potential source of cytokines has suggested
      new ways in which mast cells can act in immunological and inflammatory responses.
      In this study we have used the HMC-1 cell line as a model for human mast cells to
      study the constitutive and inducible mRNA expression of interleukins, colony
      stimulating factors, interferons, tumour necrosis factors alpha and beta, tumour
      growth factor beta and platelet-derived growth factor A and B. We found that HMC
      1 cells constitutively expressed mRNA for TNF-alpha and TGF-beta, and a low level
      of M-CSF. After treatment with the phorbol ester TPA or the calcium ionophore
      ionomycin expression of several cytokines, i.e. IL-1 beta, IL-3, IL-6, GM-CSF,
      TNF-beta and PDGF-A, could be detected. Both TPA and ionomycin induced the same
      set of cytokines, but the effect of TPA was more prominent. The relative
      induction was calculated to be 70X for IL-1 beta and IL-3, 30X for GM-CSF and
      PDGF-A and 3 - 10X for IL-6, M-CSF and TNF-beta. This study shows that human mast
      cells have the capacity to express not only cytokines mediating an immune
      response but also cytokines affecting other cell types, e.g. fibroblasts and
      endothelial cells, involved in later steps of the inflammatory response.

PMID- 7631147
TI  - Characterization of TAP-independent and brefeldin A-resistant presentation of
      Sendai virus antigen to CD8+ cytotoxic T lymphocytes.
AB  - H-2Kb-transfected T2 cells, which lack both TAP1/2 and LMP2/7 genes, are able to
      efficiently process and present Sendai virus Antigen to Kb-restricted Sendai
      virus-specific CTL. This presentation is not inhibited by Brefeldin A (BFA). Here
      we extend our analysis of this novel antigen presentation pathway. We show that
      presentation of Sendai virus antigen was not due to sensitization of T2Kb cells
      by peptides in the virus preparation or peptides released from virus infected
      cells. Also, the ability to present Sendai virus in a BFA resistant fashion was
      specific for cells of the T2 lineage. Re-expression of TAP1/2 genes in T2Kb cells
      did not alter the capability to present antigen in a BFA resistant fashion, i.e.
      the presence of a functional TAP transporter complex did not relocate (all)
      peptides to the classical pathway for antigen processing and presentation. We
      found that co-infection of T2Kb cells with either Sendai virus plus influenza
      virus or Sendai virus plus VSV did not relocate presentation of influenza or VSV
      antigen to the TAP independent BFA resistant antigen presentation pathway.
      Peptide elution experiments and studies with peptide-specific CTL firmly
      demonstrated that the antigen presented by T2Kb cells after infection with Sendai
      virus was the natural Sendai virus epitope NP324-332. The same epitope, when
      expressed as a minigene in vaccinia virus, could be presented also by T2Kb cells
      but this presentation could be blocked by BFA. Thus, the TAP independent BFA
      resistant presentation of antigen seem cell (T2 lineage) and virus (Sendai virus)
      specific, but not epitope specific. The ability of T2Kb cells to present Sendai
      virus antigen in a TAP independent BFA resistant fashion was only partially
      blocked by lysosomal inhibitors such as methylamine, ammonium chloride and
      chloroquine. These findings demonstrate that TAP1/2-independent and BFA-resistant
      class I processing is only expressed in certain cell types, in parallel with
      classical MHC class I processing, and that Sendai virus selectively can enter
      this pathway. Hypothetical models for the TAP-independent class I processing are
      discussed.

PMID- 7631149
TI  - Complement resistance of parasites.
AB  - The complement system is a first-line defence mechanism against parasites. All
      parasites causing deep infections and getting into contact with human plasma
      must, in one way or another, avoid the destructive effect of this powerful
      defence system. Several specific strategies of complement resistance of parasites
      have been reported, and this rather large spectrum of regulatory mechanisms
      covers the whole cascade of complement activation. Analysis of the known and
      elucidation of the yet unknown mechanisms will probably help in the development
      of new therapeutic and preventive approaches to control the different parasitic
      diseases. This paper will review the complement resistance mechanisms reported
      and their utilization by various parasites.

PMID- 7631150
TI  - Structural analysis of VH4-21 encoded human IgM allo- and autoantibodies against
      red blood cells.
AB  - We have sequenced the variable heavy chain regions of a number of VH4-21 encoded
      monoclonal IgM anti-Rh(D) antibodies produced in response to deliberate
      immunization. These were compared with the sequences of similarly encoded IgM
      anti-I cold agglutinins (CA) derived from patients with lympho-proliferative
      diseases. The anti-Rh(D) antibodies show evidence of clonal expansion and somatic
      diversification. Even though they are produced in response to an antigenic
      stimulus, they demonstrate limited hypermutation in the variable heavy chain (VH)
      segments and there is no evidence of selective pressure acting on the
      complementarity determining regions (CDRs). The CA demonstrate a higher rate of
      mutation and yet this results in a lower ratio of replacement to silent mutations
      (R:S) in the CDRs than seen in the anti-Rh(D) antibodies. It is not clear whether
      the different pattern of mutations seen in the CA is related to their auto
      reactivity or their tumour origin. In both groups of antibodies the region
      encoded by the VH4-21 segment can be found in germline configuration at the amino
      acid level indicating that other V-gene structures, i.e. light chains or CDRH3s,
      are crucial to the generation of either specificity. A role of the CDRH3 is
      indicated by the identification of a motif shared by four CAs and one Rh(D)
      antibody which also demonstrates CA activity independent of its anti-Rh(D)
      specificity. Amongst the anti-Rh(D) antibodies there seems to be an obligatory
      combination with VL having closest homology to the DPL16 germline segment
      indicating this as particularly important in generation anti-Rh(D) specificity.

PMID- 7631151
TI  - The aetiology of mixed cryoglobulinaemia associated with hepatitis C virus
      infection.
AB  - A strong association of hepatitis C infection (HCV) with 'essential' mixed
      cryoglobulinaemia has been established. The demonstration of HCV in Type II mixed
      cryoglobulins with monoclonal rheumatoid factors (mRF) that bear the WA
      crossidiotype has lead to the hypothesis that mixed cryoglobulins result from
      chronic stimulation by HCV-lipoprotein of a population of XId WA+B-1a cells. The
      reactivity of WA IgM initially produced is with the HCV-self antigen complex with
      RF activity resulting secondarily from the pausi-mutational process accompanying
      the T cell independent process. This benign proliferation progresses by multi
      step mutations to malignancy in a minority of patients. The implications of the
      hypothesis for understanding the physiology of certain natural auto antibodies
      and for therapeutic intervention in this disease are discussed.

PMID- 7631152
TI  - The role of thymocytes in regulating thymic epithelial cell growth and function.
AB  - The basic tenet underlying the present work and supported by recent studies is
      that there is a dialogue between developing thymocytes and thymic stromal cells.
      One direction in this dialogue, i.e. thymic stromal cell role in shaping
      thymocyte maturation, has been extensively studied. The other direction,
      thymocyte effect on stromal cell development and function, started to emerge only
      recently on the basis of in vivo observations in SCID and knockout mice. An in
      vitro approach to the analysis of this interaction may add substantial insight
      into the process, as demonstrated by the present work. We made use of a culture
      system of either murine thymic epithelial cells (TEC line) cultured alone or
      cocultured with thymocytes. Unstimulated thymocytes or their supernatant caused
      40-80% inhibition of TEC cell proliferation, as measured by 3H-thymidine
      incorporation. Cell cycle analysis by flow cytometry indicated that this
      inhibition can be attributed to reduction in G2/M phase cell number pari passu
      with an increase in Go/G1 cell number. This inhibitory effect was found to be
      partially mediated by TGF-beta produced by thymocytes. On the other hand,
      thymocytes augmented IL-6 production by TEC cells in coculture, an effect which
      could not be reproduced by thymocyte culture supernatant and was not inhibited by
      thymocyte pretreatment with formaldehyde or emetine. Furthermore, antibodies
      against thymocyte adhesion molecules (CD2, LFA-1) blocked the thymocyte-induced
      IL-6 secretion. IL-6 was found to be an autocrine growth factor of TEC in
      culture, since a combination of anti IL-6 and anti IL-6 receptor antibodies
      caused 70% inhibition of TEC proliferation and addition of exogenous recombinant
      IL-6 doubled the rate of proliferation. These results suggest that thymocytes
      regulate thymic epithelial cell growth by a complex set of inhibitory and
      enhancing signals mediated through either soluble factors or direct contact. The
      ultimate effect is dependent on the balance between different signals and may be
      different in different microenvironmental settings in vivo. In coculture in vitro
      the dominant effect was growth inhibition of the epithelial cells by thymocytes.

PMID- 7631153
TI  - Lamina propria T cell subsets in the small and large intestine of euthymic and
      athymic mice.
AB  - We investigated lamina propria T cells from the small intestine (jejunum/ileum)
      and the large intestine (colon) of euthymic (BALB/c, C.B-17, C57BL/6) and athymic
      (C57BL/6 nu/nu; BNX bg/bg nu/nu xid/xid) mice. CD3+ T cells represented about 40%
      of the lamina propria lymphocytes (LPL) from the small or the large intestine of
      euthymic mice, and 20-30% of the LPL populations from the small or large
      intestine of athymic mice. In the lamina propria T cell population of the small
      intestine, 85% were of the alpha beta lineage in euthymic mice, but only 40% were
      of the alpha beta lineage in athymic mice. T cells of the gamma delta lineage
      were thus more frequent than T cells of the alpha beta lineage in the intestinal
      lamina propria T cells of extrathymic origin. CD4+ T cells represented 40% of the
      lamina propria T cells in the small as well as in the large intestine of euthymic
      mice, and 20-30% of the T cells in the lamina propria of the nude mouse gut. In
      euthymic mice, 40% of the T cells in the small intestine lamina propria, and 30%
      of the T cells in the colonic lamina propria were CD8+. In intestinal lamina
      propria T cell populations of athymic mice, the CD8+ T cell population was
      expanded. Most (60-70%) CD8+ T cells in the lamina propria of the small and the
      large intestine of euthymic and athymic mice expressed the homodimeric CD8 alpha
      + beta- form of the CD8 coreceptor. A fraction of 15-20% of all CD3+ T cells in
      the lamina propria of the small and the large intestine of euthymic and athymic
      mice were 'double negative' CD4- CD8-. A large fraction of the TCR alpha beta + T
      cells in the colonic lamina propria (but not in the small intestine lamina
      propria) of euthymic mice expressed the CD2 and the CD28 costimulator molecules,
      the adhesion molecule LECAM-1 (CD62 L), and could be activated in vitro by CD3
      ligation. These data reveal a considerable heterogeneity in the surface phenotype
      and the functional phenotype of murine lamina propria T cells.

PMID- 7631154
TI  - Platelets contain interleukin-1 alpha and beta which are detectable on the cell
      surface after activation.
AB  - Activated platelets have been shown previously to exhibit membrane-bound IL-1
      bioactivity, which leads to the question of localization of the cytokine in
      platelets. Using immunocytological and flow cytometric techniques, we found IL-1
      alpha and IL-1 beta in the cytoplasma of both resting and thrombin-activated
      platelets. Immunogold-silver staining of the cell surface of activated platelets
      as well as preembedding antibody treatment of platelets revealed the presence of
      IL-1 (alpha and beta) in low density on the surface of intact cells in contrast
      to distinct enrichment in the cytoplasma of damaged platelets. Fibrin fibres
      present between cells indicated adsorbance of IL-1. There was also weak binding
      of anti-IL-1 alpha to the surface of thrombin-activated platelets as shown by
      flow cytometry. Following activation there appears to be some transfer of IL-1
      onto the cell surface of activated cells, the bulk of the cytokine, however, is
      probably not released prior to platelet disintegration. In summary, we present
      evidence for the presence of both IL-1 alpha and IL-1 beta in resting and
      activated platelets without being able to demonstrate localization of the
      cytokines to specific subcellular structures.

PMID- 7631155
TI  - Mechanisms by which the I-ABM12 mutation influences susceptibility to
      experimental myasthenia gravis: a study in homozygous and heterozygous mice.
AB  - The I-Abm12 mutation in C57B1/6 (B6) mice yields the B6.C-H-2bm12 (bm12) strain,
      which is resistant to Experimental Myasthenia Gravis (EMG) induced by
      immunization with Torpedo acetylcholine receptor (TAChR), while the parental B6
      strain is highly susceptible to EMG. CD4+ cells from bm12 mice immunized with
      TAChR do not recognize three sequence regions of the TAChR alpha subunit which
      dominate the CD4+ cell sensitization in B6 mice. We immunized with TAChR bm12, B6
      and (bm12 x B6)F1 mice. B6 and F1 mice developed EMG with comparable frequency.
      Their CD4+ cells recognized the same TAChR alpha subunit peptide sequences (T
      alpha 150-169, T alpha 181-200 and T alpha 360-378). CD4+ cells from TAChR
      sensitized F1 mice were challenged with TAChR and alpha subunit epitope peptides,
      using F1, B6 or bm12 APC. B6 and F1 APC presented all these Ag efficiently, while
      bm12 APC presented TAChR and peptide T alpha 150-169 poorly and erratically. Anti
      TAChR and anti-alpha subunit epitope CD4+ lines propagated from F1 and B6 mice
      had similar TcR V beta usage. All lines but those specific for the sequence T
      alpha 150-169 had unrestricted V beta usage. Anti-T alpha 150-169 lines from both
      B6 and F1 mice had a strong preferential usage of V beta 6. Anti-T alpha 150-169
      lines from F1 mice had also a slightly higher V beta 14 usage. B6, bm12 and F1
      mice developed similar anti-TAChR Ab titres, and had Ab bound to muscle AChR in
      comparable amounts. Therefore EMG resistance of bm12 mice must be due to a subtle
      shift in the anti-AChR Ab repertoire, and absence of special Ab able to cause
      destruction and/or dysfunction of muscle AChR. This is probably related to the
      absence of CD4+ cells sensitized to epitopes within the sequence T alpha 150-160,
      consequent to the inability of the I-Abm12 molecule to present this sequence.

PMID- 7631156
TI  - Induction of tolerance to experimental anti-phospholipid syndrome (APS) by
      syngeneic bone marrow cell transplantation.
AB  - Previously, we have shown the ability to induce experimental autoimmune
      conditions (e.g. SLE, APLS, Wegener's granulomatosis) following active
      immunization with the pathogenic autoantibody emulsified in adjuvant. The mice
      first develop anti-autoantibodies (Ab2: anti-id) and eventually generate anti
      anti-autoantibodies (Ab3: anti-anti-id) which carry the same antigen binding
      characteristic as the autoantibody (Ab1). The appearance of the specific
      autoantibodies in mice sera was associated with the emergence of the compatible
      laboratory and with the clinical findings characteristic to the respective
      autoimmune disease. The effects of syngeneic bone marrow transplantation (BMT) on
      experimental anti-phospholipid syndrome (APS) were investigated. BALB/c mice were
      immunized with anti-cardiolipin monoclonal antibody (MoAb) named CAM and
      developed elevated serum titres of anti-phospholipid Abs accompanied by prolonged
      activated partial thromboplastin time, thrombocytopenia and a high percentage of
      fetal resorptions. These mice were then lethally irradiated and transfused with
      bone marrow (BM) cells (T cell depleted) from syngeneic naive mice. The titres of
      antiphospholipid antibodies were reduced in the recipients. The decrease in titre
      of autoantibodies was found to be related to depletion of antibody forming cells
      in vivo, associated with reduced proliferative response of lymph node cells to
      anti-cardiolipin MoAbs. The recipients showed improvement in clinical parameters
      following syngeneic BMT. The same recipients developed specific unresponsiveness
      to a second challenge with the anticardiolipin MoAb (CAM), but developed
      experimental systemic lupus erythematosus upon immunization with a monoclonal
      anti-DNA antibody. We conclude that acute myeloablative immunosuppression
      combined with syngeneic bone marrow transplantation may induce a state of
      tolerance to the pathogenic autoantibodies in mice with experimental APLS. Our
      results suggest that a similar approach may be useful in treating life
      threatening autoimmune syndromes (e.g. catastrophic APLS) in clinical practice.

PMID- 7631157
TI  - Construction and adhesive properties of a soluble MadCAM-1-Fc chimera expressed
      in a baculovirus system: phylogenetic conservation of receptor-ligand
      interaction.
AB  - MAdCAM-1 is a high endothelial venule adhesion molecule composed of
      immunoglobulin and mucin-like domains which binds the leucocyte integrin LPAM-1
      (alpha 4 beta 7), and is largely responsible for the selective homing of
      lymphocytes to mucosal tissues. A novel soluble form of mouse MAdCAM-1 which is
      normally membrane bound has been produced by joining the extracellular region of
      the receptor to the Fc domain of human IgG1. The MAdCAM-1-Fc cDNA was inserted
      into the genome of Autographa californica nuclear polyhedrosis virus (AcNPV).
      Spodoptera frugiperda insect cells infected with the recombinant virus produced
      MAdCAM-1-Fc as a disulfide-linked homodimer of 82 kDa polypeptides, which was
      secreted into the culture medium at > 1 microgram/ml. The product purified by
      Protein G-Sepharose was identified as authentic MAdCAM-1-Fc by the anti-MAdCAM-1
      monoclonal antibody (MoAb) MECA-367 using Western blot and ELISA analysis. When
      immobilized on glass it was fully functional in supporting the binding of mouse
      alpha 4 beta 1+ alpha 4 beta 7+ mesenteric lymph node lymphocytes, and the alpha
      4 beta 1- alpha 4 beta 7+ TK1 T cell lymphoma. Binding was enhanced by Mn(++)
      induced integrin activation, and specifically blocked by anti-integrin alpha 4
      subunit and anti-MAdCAM-1 MoAbs. Binding was blocked by pretreatment of cells
      with sodium azide, and EDTA, indicating that binding is an energy-dependent
      process which requires divalent cations. Thus the mouse MAdCAM-1-Fc chimera
      produced in insect cells retains certain functional properties that typify the
      native receptor, and should be valuable in analysing the role of MAdCAM-1 in
      lymphocyte recirculation and emigration. However it was not sialylated despite
      being post-translational modified with N- and O-linked carbohydrate moieties,
      suggesting that the ability of MAdCAM-1 to support cell adhesion under static
      conditions is sialylation-independent. A rabbit polyclonal antibody raised
      against the entire cytoplasmic domain of the human integrin beta 7 subunit
      recognized LPAM-1-like molecules in human, rat, and mouse cells, suggesting a
      high degree of conservation of the MAdCAM-1 receptor across species. In agreement
      with this notion MAdCAM-1-Fc immobilized on glass was fully functional in
      supporting the cation-dependent binding of peripheral blood or spleen cells from
      a range of other species including human, rat, and guinea pig; and for human
      myeloid HL60 cells, binding was mediated by alpha 4 integrins.

PMID- 7631158
TI  - The influence of non-HLA genes on the human T-cell receptor repertoire.
AB  - We previously demonstrated a central role for HLA genes in determining the T-cell
      receptor (TCR) repertoire. However, these studies also suggested that other
      genetic factors might also play a role in the development of this repertoire. In
      order to assess the role of non-HLA genes in the development of the TCR
      repertoire, we have analysed and compared the TCR repertoires of individuals in
      three families consisting of both monozygotic twins as well as an HLA-identical
      sib. TCR repertoire analysis was performed with both V-segment-specific MoAb and
      the polymerase chain reaction using TCRBV-segment-specific oligonucleotide
      primers. We observed that in every case the TCR repertoires of identical twins
      were more similar to each other than to their HLA-identical sib. Furthermore, in
      one family we were able to show by genotype analysis that most of the differences
      in repertoire between the identical twins and their HLA-identical sib were caused
      by polymorphisms in the TCR genes that influence expression levels. These studies
      document an important role for non-HLA genes in determining the TCR repertoire in
      man and raise the possibility that such TCR polymorphisms may play a significant
      role in determining disease susceptibility.

PMID- 7631159
TI  - Two nuclear dot-associated proteins, PML and Sp100, are often co-autoimmunogenic
      in patients with primary biliary cirrhosis.
AB  - The nucleoproteins Sp100 and PML, the first an autoantigen predominant in
      patients with primary biliary cirrhosis (PBC) and the second a transformation and
      cell growth suppressing protein aberrantly expressed in promyelocytic leukaemia
      cells, were recently shown to colocalize in dot-like nuclear domains. Here we
      analysed whether PML, like Sp100, is also an autoantigen in patients with PBC and
      other autoimmune diseases, and wether both proteins interact directly. Testing
      sera from autoimmune patients using an immunoprecipitation assay with
      radiolabelled PML and an immunofluorescence assay based on a cell line
      overexpressing PML, autoantibodies (Aabs) against PML were found in the majority
      o anti-Sp100 Aab positive patients. Only very few patients with PBC or other
      autoimmune diseases contained anti-PML or anti-Sp100 Aabs exclusively. In
      contrast to Sp100, immunoreactivity of recombinant PML in immunoblots was only
      weak and was directed to one region. This suggests that anti-PML Aabs recognize
      fewer and preferentially conformation-dependent epitopes. In an
      immunoprecipitation assay using in vitro synthesized Sp100 and PML proteins and
      Abs to recombinant proteins, no direct interaction was observed. Taken together,
      these data indicate that Aabs against PML are as highly prevalent and specific
      for patients with PBC as those against Sp100. The colocalization of these
      autoantigens and the frequent co-occurrence of the corresponding Aabs might
      reflect an association of both proteins mediated by one or several other
      proteins.

PMID- 7631160
TI  - Systemic and secretory humoral immunity in the normal human vaginal tract.
AB  - The molecular status of Abs in the vaginal fluid is reconsidered as a basis for
      immunization strategies for women' vaccination against HIV. Analysis of separated
      immunoglobulins (Igs) shows a large proportion of uncleaved IgG, whereas the low
      amount of IgA includes SIgA, monomers and fragments. SIgM is at a very low level,
      while free SC molecules are abundant. In addition to the already documented local
      synthesis, vaginal IgG contains serum-derived tetanus antitoxins. The IgG could
      reach the lumen by diffusion, and/or be transported by an Fc receptor-associated
      mechanism as suggested by the subclass imbalance in favour of the IgG1 isotype.
      VAginal SIgA contains very low levels of antibodies o the cell-well carbohydrates
      from a dental caries-associated streptococcus confirming the participation of the
      secretory immune system. IN addition, the low percentage of IgA2 suggests tha a
      proportion of vaginal SIgA can also derive from actively transported serum
      polymers. In agreement with our previous studies showing induction of vaginal
      tetanus antitoxins by intramuscular immunization, these results are in favour of
      classical, parenteral vaccinations to induce protection of the human vagina.

PMID- 7631161
TI  - Alterations of the post transplant blood lymphocyte phenotype subsets as a marker
      of rejection in renal allograft recipients.
AB  - The postoperative alterations of absolute levels of lymphocyte phenotype subsets
      in peripheral blood were studied in recipients of living donor renal allografts
      and in kidney donors. The results were expressed as per cent changes of the
      preoperative values. The lymphocyte subsets, CD3, CD4 and CD8 cells, decreased to
      approximately 50% following the surgical trauma, with rapid recovery to
      preoperative levels within 1 week in kidney donors and in recipients without
      rejection episodes. In contrast, the T-cell levels in recipients with rejection
      episodes remained low after 1 week, before clinical signs of rejection, and was
      predictive for the later occurrence of acute rejection episodes. The T-cell
      levels in the recipients with rejection episodes remained low during the first 6
      weeks, maybe due to the rejection treatments given during this period. The B
      lymphocytes were not affected in any of the recipient groups. The alterations
      observed were not explained by CMV infections, which occurred mainly after the
      observation period of 6 weeks. In conclusion, the operation per se induced
      alterations in circulating T-lymphocyte subsets and low T-cell levels after 1
      week were predictive of rejection episodes.

PMID- 7631162
TI  - Molecular analyses of anti-DNA antibodies induced by polyomavirus BK in BALB/c
      mice.

PMID- 7631163
TI  - Could schizophrenia be a viral zoonosis transmitted from house cats?
AB  - Studies have suggested that some cases of schizophrenia may be caused by viruses.
      We hypothesize that such cases may be cases of viral zoonosis transmitted
      primarily from house cats. Epidemiological aspects of schizophrenia and a case
      control questionnaire support this hypothesis.

PMID- 7631164
TI  - Evaluation of Torrey and Yolken's feline viral zoonosis theory of schizophrenia.
AB  - A formal method of evaluation is applied to a theory presented by Drs. Torrey and
      Yolken, which asserts that cases of viral schizophrenia are due to a zoonosis
      from house cats. A formal method of theory evaluation is described, and the
      Torrey and Yolken theory is subjected to analysis by the method. The theory is
      found to be weak in several areas stemming from inadequate description of both
      the relevant clinical population and the viral pathogenesis, as well as an
      incomplete examination of available data bearing on a hypothesized association
      between schizophrenia and cat ownership. At this point, further work is indicated
      at the level of theory development before proceeding with research or clinical
      activity.

PMID- 7631165
TI  - Israeli High Risk Study: editor's introduction.
AB  - The National Institute of Mental Health joint study by the United States and
      Israel, known as the Israeli High-Risk Study,is a unique long-term followup
      investigation of children at genetic risk for schizophrenia. We compared the
      development of psychiatric disorder in two groups of such children, one group
      raised in kibbutz environments, the other by their own parents. Matched controls
      were studied as well. The subjects were evaluated at ages 11, 17, and 26; an
      extensive battery of cognitive and clinical tests, as well as psychophysiological
      and diagnostic procedures, was used. This issue of the Schizophrenia Bulletin
      reports and summarizes evaluations conducted when the subjects were in their
      early thirties, as well as some previously unreported data obtained when the
      subjects were 17 years old.

PMID- 7631166
TI  - Twenty-five-year followup of the Israeli High-Risk Study: current and lifetime
      psychopathology.
AB  - Current and lifetime psychopathology was assessed in 50 Israeli children of
      parents with schizophrenia who were either of kibbutz families and raised
      collectively with the help of child care workers, or of urban families and raised
      by their parents. Index subjects were compared with 50 matched control children
      of healthy parents by means of the Schedule for Affective Disorders and
      Schizophrenia-Israel. Subjects were evaluated in adulthood at a mean age of 31
      years; schizophrenia was found exclusively among children of ill parents, and no
      effect of town or kibbutz rearing on risk for schizophrenia was observed. Major
      affective illness was more common among kibbutz index subjects. Affective
      symptomatology observed in some index parents was evenly distributed among town
      and kibbutz parents and was not related to the diagnosis of affective disorders
      in at-risk children. Current adult functioning was similar between town-and
      kibbutz-raised subjects (and in general reflected good adjustment); an excess of
      personality disorders was found among index subjects. The present findings
      support the concept that both familial and environmental factors operate in the
      expression of psychopathology.

PMID- 7631167
TI  - Neuropsychological assessment of attention and its pathology in the Israeli
      cohort.
AB  - We assessed attention in 63 of the 98 traceable living subjects of the original
      100 in the National Institute of Mental Health (NIMH) joint study of
      schizophrenia by the United states and Israel, known as the Israeli High-Risk
      Study cohort; their mean age was 32 years. These data were supplemented, for
      comparative purposes, with those obtained on 31 normal control and 17
      schizophrenia subjects studied at NIMH.  The results suggest that attention
      skills of the adult children of a parent with schizophrenia fall between those of
      schizophrenia patients and controls, and that measures of sustained attention and
      the ability to focus and execute provide the best discrimination among groups.
      Post hoc analyses revealed that poor scores on simple tests of attention obtained
      in childhood were associated with the development of disorders in adulthood. Low
      scores on a digit cancellation test at age 11, but not at age 17, predicted which
      of the children at genetic risk would develop schizophrenia spectrum disorders
      diagnosed at ages 26 and 32.

PMID- 7631168
TI  - Reanalysis of SCOR and anxiety measures in the Israeli High-Risk Study.
AB  - In an earlier study, skin conductance orienting response (SCOR) and anxiety
      measures obtained when the subjects of the Israeli High-Risk Study were 11 years
      old were analyzed, using adult diagnostic information, when the subjects were 26
      years old. The present study considers similar data obtained from most of this
      sample when the subjects were 16 years old. As in the earlier analysis, those
      subjects who would receive a schizophrenia spectrum diagnosis at 26 had higher
      anxiety ratings at age 16. Nondiagnosed index subjects also had significantly
      higher anxiety ratings than the nondiagnosed controls. The subjects who would
      receive affective spectrum diagnoses at age 26 had the most hyporesponsive SCORs,
      as predicted, while the subjects who would later be diagnosed in the
      schizophrenia spectrum had an unexpected hyperresponsive SCOR to the
      dishabituation tone in a habituation series. Further consideration of the long
      term stability of SCORs seems necessary; they may be related to the developing
      psychopathological processes.

PMID- 7631169
TI  - Locus of control and mental health in adolescence and adulthood.
AB  - Eighty-nine subjects of the original sample of the National Institute of Mental
      Health joint study by the United States and Israel, known as the Israeli High
      Risk Study, were given a clinical interview and a questionnaire measuring locus
      of control (LOC) during the second phase of the study, when the subjects were
      adolescents. During phases 3 and 4, approximately 8 and 15 years later, the
      subjects were psychiatrically assessed and 56 of them repeated the LOC
      questionnaire.  The two measures of LOC were correlated, as were general
      assessments of mental health (MH). Adolescent LOC was related to lifetime MH,
      although LOC and MH were not related to each other concurrently in either
      adolescence or adulthood. The best predictive model for lifetime MH outcomes was
      a combination of adolescent MH and LOC variables; background variables, including
      parental schizophrenia, were superfluous. The data suggest that whereas
      adolescent MH is the best predictor of general MH, adolescent LOC is the better
      predictor of schizophrenia and major affective disorders.

PMID- 7631170
TI  - Overview and summary: twenty-five-year followup of high-risk children.
AB  - We report a 25-year followup of a group of 50 children at genetic risk for
      schizophrenia (by virtue of having a parent with the disorder) and 50 matched
      controls. The children who eventually developed schizophrenia spectrum disorders,
      including schizophrenia, were identifiable by cognitive-psychophysiological,
      neurointegrative, and social/personality traits in the preteenage period. The
      children at risk were also more likely to develop other Axis I disorders, chiefly
      affective. Moreover, the risk of Axis I disorders was significantly greater among
      children raised in the group atmosphere of a kibbutz than among those raised in
      their own nuclear families in cities and towns in Israel. The study is a unique
      contribution to knowledge of factors underlying the development of
      psychopathology.

PMID- 7631171
TI  - Cerebellum and schizophrenia: a selective review.
AB  - Structural and functional brain imaging have contributed significant data to our
      understanding of schizophrenia, but we are still unable to understand the
      presumably heterogeneous neuronal dysfunctions of schizophrenic disorders.
      Current disease models define schizophrenia as an exclusively forebrain disorder.
      Nevertheless, morphological and functional data support the authors' view that
      cerebellar dysfunction may contribute to schizophrenic disorders. This article
      presents a critical review of neurological signs, including results of a clinical
      study performed by the authors, as well as postmortem and neuroimaging findings
      of cerebellar pathology in schizophrenia patients and studies on other
      psychiatric features associated with cerebellar lesions. In addition, anatomical,
      physiological, and behavioral data are reviewed that argue in favor of cerebellar
      involvement in nonmotor brain functions. A particular cerebellar region, the
      anterior vermis and corresponding fastigial nucleus, is assumed to be important
      in schizophrenic disorders, and the neurochemistry and vermian-fastigial
      forebrain pathways are shown to correspond well with current hypotheses on
      neurotransmitter imbalances in schizophrenia. Therapeutic implications are
      outlined.

PMID- 7631172
TI  - Neuropsychological correlates of violence in schizophrenia.
AB  - Thirty-one outpatient men with schizophrenia were assessed with various measures
      of lifelong history of physical violence as well as psychopathology,
      neuropsychological performance, and neurological intactness. Most of the results
      consisted of nonsignificant positive relationships between physical aggression
      and neuropsychological performance in these schizophrenia subjects. Some
      neuropsychological test performances did show significant positive correlations
      with levels of aggressivity. In contrast with previous studies that have
      established a relation between neuropsychological impairment (as opposed to
      performance) and violence in schizophrenia, subjects of the present study were
      high-functioning outpatients who may not have attained a level of neurological
      impairment inducing constant uncontrollable outbursts of irritative aggression in
      their daily living. The importance of defining in detail the clinical
      characteristics of the subjects studied and the type of violence assessed is
      discussed, and an ecological interpretation of these counterintuitive results is
      provided.

PMID- 7631173
TI  - Clozapine increases EEG photic driving in clinical responders.
AB  - Photically driven electroencephalography was tested in 17 chronic schizophrenia
      patients who were treated with clozapine for 5 weeks. Eight of the 17 patients
      showed clinical improvement on the Brief Psychiatric Rating Scale (delta BPRS >
      30%) while the other 9 patients remained unchanged (delta BPRS < 15%). In
      comparison with the nonresponders, clozapine responders had a significantly
      greater increase in photic driving in the electroencephalogram (EEG), primarily
      in the low-frequency range of alpha band (7.2 hertz [Hz], 8.3 Hz, 9.0 Hz, and 9.6
      Hz, but not 12.0 Hz). The difference in the resting EEG between the responders
      and nonresponders did not reach statistical significance. These findings
      suggested that EEG photic driving might be more sensitive than the resting EEG in
      detecting the central nervous system drug effect. Further analysis revealed that
      the increase of EEG photic driving was positively correlated with patients'
      clinical improvement. Combined with our previous observation in the drug-free
      schizophrenia patients who had lower EEG photic driving, present results
      supported the hypothesis that the amount of EEG alpha activity, particularly its
      synchronization to the external stimuli, could reflect the thalamic function in
      sensory information processing in schizophrenia.

PMID- 7631174
TI  - Information processing and social competence in chronic schizophrenia.
AB  - The relationship between social competence and information processing among
      individuals with chronic schizophrenia was investigated. Thirty-eight inpatients
      participated in a role play test of social competence and completed a battery of
      information-processing tasks. Information processing was found to be
      significantly related to social competence, even after controlling for patient
      demographics, chronicity, and symptomatology. Higher global social competence was
      related to more efficient early information processing on a continuous
      performance/span of apprehension task. Composite indices of specific social
      competence (i.e., paralinguistic and nonverbal skills) were related to other
      aspects of information processing (e.g., reaction time). Implications for
      behavioral assessment and cognitive rehabilitation are discussed.

PMID- 7631175
TI  - Individual psychotherapy and persons with serious mental illness: the clients'
      perspective.
AB  - The perspectives of persons with serious mental illness about their experiences
      with individual psychotherapy were obtained from a stratified random sample of 12
      psychosocial rehabilitation centers from all centers in Maryland. Response and
      completion rates, test-retest reliability, and generalization data were positive.
      Eight areas were explored: (1) Utilization and duration: of the 212 respondents,
      90 percent had been in therapy for a median of 12 months (mean = 3 years); only a
      third expected to end their therapy within 5 years. (2) Therapeutic
      effectiveness: most of the respondents (72%) reported that individual
      psychotherapy had brought positive changes to their lives, 14 percent reported
      negative changes, and 14 percent reported that therapy had had no effect. (3)
      Preferred interventions and parameters: sixteen percent felt that medication was
      most useful, 25 percent felt that talking therapy was most useful, and 60 percent
      endorsed a combination of the two. With respect to diagnosis and psychotherapy,
      84 percent of respondents with schizophrenia preferred brief, less frequent
      sessions of reality-oriented therapy over longer, more frequent sessions of
      insight therapy. Respondents with bipolar and major depression were equally split
      between the two. (4) Therapeutic issues: human concerns were more frequently
      rated as important and were rated higher in importance than illness-specific
      symptoms. (5) Clients' view of illness: Only 8 percent thought their illness was
      a brain disease, a third thought it was a psychological problem, and a quarter
      thought it was a combination of both; a third answered, open quote I don't know
      closed quote. Almost half did not know what their therapists thought. (6)
      Therapeutic relationship: Friendliness was the quality most desired in a
      therapist. (7) Confidentiality: Most felt that therapists generally kept the
      clients' confidences. (8) Empowerment: Persons who felt empowered in therapy
      spent less time in hospitals, expected a shorter stay in therapy, and knew more
      about their problems. Suggestions are made about a more client-responsive model
      of individual psychotherapy for persons with serious mental illness.

PMID- 7631176
TI  - Schizophrenia among Hispanics: epidemiology, phenomenology, course, and outcome.
AB  - A number of studies point to the influence of culture and ethnicity on the
      presentation and course of schizophrenia. In general, a relatively powerful
      influence of environmental factors is identified. This article reviews the
      literature on schizophrenia among Hispanics in the United States and uses the
      results of this review as a basis for identifying directions for future study.
      Research is divided into three major areas: epidemiology, phenomenology, and
      illness course and outcome. Ethnic comparisons suggest similar prevalence rates
      of schizophrenia. However, differences in illness phenomenology between certain
      subgroups of Hispanics are also observed. Moreover, culture can affect various
      aspects of the illness process, including illness definition, help- seeking
      behavior, response to treatment, and post-treatment adjustment. Proposed
      guidelines to direct future research ventures include (1) better delineation of
      the sociocultural attributes of the group under study, (2) validation of
      assessment instruments across ethnic groups, (3) use of innovative approaches to
      assess incidence and prevalence, (4) incorporation of qualitative methodology,
      (5) use of illness behavior models to provide a conceptual framework to guide
      investigations, and (6) integration of cross-cultural and biological studies.

PMID- 7631177
TI  - Assessment of alcohol and other drug disorders in the seriously mentally ill.
AB  - Brief assessment methods are needed to determine the presence of alcohol and drug
      problems in persons with severe mental illness. The purposes of this study were
      to determine the prevalence of alcohol and other drug problems in a rural
      population of 253 clients with severe mental illness and to determine the
      accuracy of case manager responses to specific alcohol and drug assessment
      questions about their clients. Clients were assessed for the presence of past and
      present alcohol and drug disorders by means of a face-to-face diagnostic
      interview. The specific questions the case managers were asked to complete were
      designed to assess the quantity and frequency of recent alcohol and drug use and
      the presence of three criteria for alcohol or drug dependence and to
      differentiate present versus past history of substance problems. On the basis of
      the Diagnostic Interview Schedule- Revised, 35 percent of the clients met current
      DSM-III-R alcohol or drug criteria for abuse, dependence, or both. There were
      differences between client and case manager reports on the clients' use of
      alcohol, marijuana, cocaine, narcotics, and unprescribed tranquilizers in the
      last year. The best predictor of a client's present alcohol or drug problem was
      whether the case manager thought that the client had substance use problems at
      some time in his or her life (sensitivity = 0.86, specificity = 0.75). This
      report provides additional evidence that case manager reports are a valid method
      of determining the prevalence of substance use problems in persons with severe
      mental illness.

PMID- 7631178
TI  - A clinically based rule of thumb for classifying delusions.
AB  - Conventional psychodynamic treatment assumptions sometimes warned against direct
      confrontation of a patient's delusions because delusions were believed to serve
      defensive functions. Based in part on research findings some have recently
      asserted that it can be beneficial for the clinician to challenge a patient's
      delusional beliefs. Short-term positive results from such confrontations have
      been reported. I review clinical and research considerations that may aid the
      clinician in deciding when confrontation may be beneficial. I identify a class of
      delusions that are unlikely to respond to confrontation. Alternative clinical
      responses to this class are suggested.

PMID- 7631179
TI  - First person account: a personal experience.

PMID- 7631180
TI  - [On the content].

PMID- 7631181
TI  - [The toxicity of root-canal filling materials in primary osteoclast cell
      cultures].
AB  - Endodontic root-filling material is brought into direct contact with apical
      tissues when finishing endodontic therapy. Endodontic two-component materials
      develop cytotoxic effects during the phase, as shown in different in-vitro
      studies. Insufficient specificity of these tests could be eliminated by using
      bone cell cultures. The toxicity of seven endodontic root-filling materials
      towards osteoclasts in primary cell culture were investigated. Osteoclasts
      initially reacted to freshly mixed endodontic materials by losing their
      physiological properties (surface adherence), longer exposition on the toxic
      agents led to cell lysis. To quantify these light-microscopical phenomena, the
      content of lactate dehydrogenase (LDH) in the adherent cells as well as in the
      medium of the cultures were determined photometrically. All the examined two
      component materials induced a distinct loss of intracellular LDH activity with a
      proportional uprise in the media. Calibration showed a positive correlation of
      LDH content and cell number. The results could be interpreted as the survival
      rate of osteoclasts after incubation with endodontic filling materials. All
      tested materials--except for gutta-percha--showed a distinct toxicity towards
      osteoclasts in primary cell culture during the first 24 hours. Osteoclasts proved
      to be sensitive indicators for cell-adverse toxicity during the in-vitro tests of
      endodontic root-filling materials.

PMID- 7631182
TI  - [Cariogenic carbohydrates in maltodextrins, glucose syrups and maltodextrin
      containing infant tea].
AB  - Five maltodextrins and five corn syrups each, seven instant teas containing
      maltodextrin and one tea produced on a protein-base were analysed for fermentable
      carbohydrates using enzymatic analyses test combinations and a spectrophotometer.
      Analysis of the maltodextrins and glucose syrups demonstrated the heterogenicity
      of this group of substances and also some incompleteness in the declaration of
      maltose, maltotriose and glucose, sugars typically contained in these products.
      In standard samples of the instant teas cariogenic sugars were found in
      concentrations up to 0.7%. As these sugars were not declared in any of the
      products, the consumer is not able to assess the cariogenic potential of the
      ingredient maltodextrin. The intake of products containing maltodextrins or corn
      syrups must lead to an uncontrolled sugar consumption.

PMID- 7631183
TI  - [Grinding precision and accuracy of the fit of Cerec-2 CAD/CIM inlays].
AB  - The grinding precision of one Cerec-1 (C1) and one Cerec-2 (C2) CAD/CIM unit each
      was evaluated using standardized inlay-like (mod) samples (n = 40) of Vita Cerec
      Mk II porcelain and Dicor MGC glass ceramic. Typical dimensions (B, E, F, H) of
      the sampleS were measured and the standard deviations (SD) analysed statistically
      using the F-test. SD of C2-machined sample dimensions were significantly lower
      using both Vita, B: p < 0.05; E: p < 0.001; F: p < 0.001; H: p < 0.001, and Dicor
      MGC, B: p < 0.05; E: p < 0.001; F: p < 0.001; H: p < 0.01, than those machined
      with C1, indicating a strong improvement of grinding precision of C2 compared to
      C1. Accuracy of fit to human molar cavities of mod inlays machined with C1 (n =
      6) and C2 (n = 6) was evaluated using a scanning electron microscope with 100x
      magnification. The width of the interfacial luting gap was generally lower in C2
      inlays (56 +/- 27 microns) than with C1 (84 +/- 38 microns). Significant
      differences (t-test) were seen in margin sections "cervical line angles above
      CEJ" (C1 = 124 +/- 44/C2 = 59 +/- 30 microns, p < 0.05), "cervical line angles at
      CEJ" (C1 = 109 +/- 55/C2 = 67 +/- 27 microns, p < 0.05) and "gingival margin
      above CEJ" (C1 = 81 +/- 32 microns/C2 = 31 +/- 18 microns, p < 0.05).

PMID- 7631186
TI  - ["I like my work a lot". Interview by Kurt Venner].

PMID- 7631184
TI  - [The basal cell nevus syndrome. A review of the literature and the long-term
      documentation of 3 female patients].

PMID- 7631185
TI  - [The treatment of a case of Class III. The early orthodontic treatment of a case
      of Class III: an alternative].

PMID- 7631187
TI  - [A country dentist fights for prophylaxis. Interview by Kurt Venner].

PMID- 7631188
TI  - ["The determination of the caries risk" and "Root filling and surgical
      endodontics". A report on the 9th annual meeting of the German Society for Tooth
      Preservation on 12 and 13 May 1995 in Berlin].

PMID- 7631189
TI  - [Implants: the maintenance phase and treatment of peri-implant lesions. A report
      on the course on "The maintenance phase of implants--the treatment of peri
      implant lesions" given 13 May 1995 at the Centre des congres de la Foire in
      Basel].

PMID- 7631190
TI  - [Implants--the denture of the future. A report on the 5th International
      Scientific Implantation Symposium of Friatec AG from 24 to 25 March 1995 in
      Wiesloch].

PMID- 7631191
TI  - [Different treatment methods for bone regeneration. A report on the Symposium on
      Different Treatment Methods for Bone Regeneration of Biomaterials Geistlich of 6
      April 1995 in Zurich].

PMID- 7631193
TI  - [Hygiene courses in Ticino. Interview by Ercole Gusberti].

PMID- 7631192
TI  - [Dental enamel erosion. A report of the Interuniversity Study Group for Dental
      Prophylaxis Problems (IUSP)].

PMID- 7631194
TI  - [A need to talk].

PMID- 7631196
TI  - [The place of the psychiatric nurse in the general hospital].

PMID- 7631197
TI  - [The challenge of integration].

PMID- 7631195
TI  - [A new psychiatric approach].

PMID- 7631198
TI  - [The quarrel between the ancients and the moderns].

PMID- 7631199
TI  - [The disconcerting situation in general hospitals].

PMID- 7631200
TI  - [The first professional schools for public health nurses].

PMID- 7631201
TI  - [Writings by nurses].

PMID- 7631202
TI  - Antibiotic resistance in bacteria.
AB  - Antibiotic resistance in bacteria has emerged as a medical catastrophe. This
      results from the speed at which bacteria multiply and are spread, and the ease
      with which they can change their genetic material or acquire new genes. They
      exert biochemical resistance by preventing entry of the drug, by rapidly
      extruding the drug, or by enzymatically inactivating the drug or altering its
      molecular target. The presence of antibiotics in the internal environments of
      human beings and animals provides a selective pressure for any resistant
      organisms to become predominant. Examples of antibiotic resistance in several
      important human pathogens are Streptococcus pneumoniae, enterococci,
      staphylococci, enteric bacilli, Haemophilus influenzae, Neisseria gonorrhoeae,
      Neisseria meningitidis, and Mycobacterium tuberculosis.

PMID- 7631203
TI  - Stiff-man syndrome revisited.
AB  - Stiff-man syndrome is a rare disorder characterized by involuntary axial rigidity
      and continuous motor unit activity on electromyography. Recent studies propose an
      autoimmune etiology of this disorder because antibodies directed against glutamic
      acid decarboxylase and pancreatic islet cells have been detected. Favorable
      responses to plasmapheresis have been reported, and new treatment modalities are
      being studied.

PMID- 7631204
TI  - Catfish stings in Mississippi.
AB  - We reviewed a series of 83 catfish sting cases from inland hospitals (Belzoni and
      Indianola) and a coastal hospital (Pascagoula) to identify the type and severity
      of injury, as well as the type of treatment and its effectiveness. Oral
      cephalosporin was adequate in treating early infections.

PMID- 7631205
TI  - Therapists' attitudes about treating patients with eating disorders.
AB  - The attitudes of 90 therapists toward patients with an eating disorder were
      explored by questionnaire. Topics included therapist's treatment desires,
      countertransference, treatment approaches, and prognosis. Twenty-eight
      respondents (31%) desired not to treat such patients. Analysis of those who did
      not desire to treat these patients showed that (1) more of them were male, (2)
      individual therapy as the sole treatment method was more common, (3) feelings of
      empathy were less common, and (4) more of them believed the prognosis for
      anorexia nervosa with bulimia to be poor. Overall, therapists considered
      cognitive behavioral therapy to be the preferred treatment method, though
      subjects who desired to treat these individuals tended to use more diverse
      (dynamic, supportive, interpersonal, eclectic) approaches. Twenty-nine percent of
      both groups believed female therapists were preferred. Therapist frustration,
      treatment resistance, and comorbid conditions were found problematic. This study
      revealed several factors that distinguish therapists by desire to treat
      individuals with eating disorders.

PMID- 7631206
TI  - Cerebrospinal fluid and peripheral white blood cell response to acute cerebral
      ischemia.
AB  - We prospectively evaluated the inflammatory response to acute cerebral ischemia
      in 57 patients who were seen within 72 hours of ictus. All subjects had
      cerebrospinal fluid examination, complete blood count, sedimentation rate
      determination, and body temperature monitoring. Correlation analysis was done
      between these measurements and infarct volume, which was determined by computed
      tomography of the brain. We found a positive linear correlation between infarct
      size and the peripheral white blood cell count, specifically the
      polymorphonuclear leukocyte count. A relationship was also observed for the
      cerebrospinal fluid protein level, the gamma globulin level, and the
      cerebrospinal fluid/serum albumin ratio. The correlations observed presumably
      reflect the extent of tissue injury and secondary inflammatory response in acute
      cerebral ischemia.

PMID- 7631207
TI  - Prophylactic nasogastric tube decompression: is its use justified?
AB  - To evaluate the need for routine prophylactic nasogastric tube decompression
      following gastrointestinal surgery, we retrospectively reviewed the cases of 177
      patients. The patients were classified as those not receiving nasogastric tubes,
      those whose tubes were removed within 48 hours postoperatively, and those whose
      tubes remained for more than 48 hours. No significant differences were noted in
      duration of hospital stay, time for return of adequate bowel function, or time
      before beginning an oral diet. Further, there were no differences in the
      frequency of wound complications, anastomotic leakage, or mortality. Patients
      without tubes had no greater incidence of vomiting, and despite a more frequent
      occurrence of abdominal distention and nausea, only 8% required insertion of a
      tube for persistent symptoms. Intubated patients had a greater frequency of
      respiratory complications. The results indicate that routine prophylactic use of
      nasogastric decompression is unnecessary and may be safely eliminated in patients
      having gastrointestinal surgery.

PMID- 7631208
TI  - Thionamides alter the efficacy of radioiodine treatment in patients with Graves'
      disease.
AB  - Thionamides are often used acutely to control the symptoms of thyrotoxicosis
      associated with Graves' disease before definitive treatment with radioiodine.
      Several reports have suggested that pretreatment with thionamides reduces the
      efficacy of radioiodine therapy in patients with Graves' disease, but other data
      refute this. This study retrospectively reviewed the records of 95 patients with
      Graves' disease treated with radioiodine. Pretreatment with thionamides resulted
      in significantly greater (2 1/2-fold) treatment failure rate than in patients not
      pretreated with thionamides but given a comparable dose of radioiodine. Higher
      serum thyroxine concentration at the time of diagnosis was also an independent
      factor associated with radioiodine treatment failure.

PMID- 7631209
TI  - Analysis of 11 cases of delusions of parasitosis reported to the Mississippi
      Department of Health.
AB  - Delusions of parasitosis (DOP) is a psychiatric disorder in which people have an
      unshakable false belief that they are infested with arthropod parasites. To rid
      themselves of the "bugs" patients with DOP may become desperate and quit their
      jobs, burn furniture, abandon homes, and use pesticides dangerously and
      repeatedly. Data from 11 cases of DOP, reported to the Mississippi Department of
      Health between 1989 and 1993, are presented in an attempt to identify common
      factors among the cases. Seven of the 11 patients (64%) were elderly white women.
      Five patients complained of "mites," 3 of "insects," and 3 of "bugs"; and all
      characteristically offered "proof" of their infestation such as bits of debris or
      skin scrapings wrapped in paper or in tiny jars. Only one complained of itching.
      Six patients reported extensive use of pesticides. These results elucidate the
      clinical presentation of DOP cases, thus aiding in diagnosis of the disorder.

PMID- 7631210
TI  - Epidemiology of nontyphoidal salmonellae at a tertiary care center in northeast
      Florida.
AB  - Nontyphoidal salmonellae (NTS) are often isolated from stool specimens of
      individuals having evaluation of gastroenteritis. The significance of isolation
      of NTS in a stool specimen from previously healthy individuals with
      gastroenteritis is not clear. The purpose of this study was to determine which
      serotypes were being isolated most frequently and whether some serotypes were
      responsible for the majority of infections. A 6-year review yielded 433 stool
      isolates of NTS. Only 12 isolates were from specimens other than stool. Thirty
      five different strains were isolated over the last 6-year period. The most common
      isolates were S javiana, 126 (29%); S newport, 85 (20%); S typhimurium, 47 (11%);
      S muenchen, 28 (7%); and S heidelberg, 21 (6%). These five strains were isolated
      in each of the 6 years of the review and were responsible for 313 (72%) isolates.
      The most common isolate for each year was S javiana, a strain that has not
      previously been reported as the predominant human isolate in invasive diseases or
      in outbreaks. In fact, S javiana is not even among the 10 most common NTS
      isolates reported to the Centers for Disease Control and Prevention nationally.

PMID- 7631211
TI  - Cyclosporine-induced worsening of hepatic dysfunction in a patient with Crohn's
      disease and enterocutaneous fistula.
AB  - Cyclosporine recently has become part of the treatment regimen for patients with
      refractory inflammatory bowel disease, though it is still considered
      investigational for that purpose. However, little attention has been given to the
      potential hepatotoxicity associated with cyclosporine administration. This can be
      especially significant in patients with preexisting abnormalities of liver
      function, including those induced by total parenteral nutrition.

PMID- 7631212
TI  - Cryptococcal pneumonia simulating chronic eosinophilic pneumonia.
AB  - We report two cases of cryptococcal pneumonia in which the roentgenographic
      picture closely mimicked that for chronic eosinophilic pneumonia. Caution in use
      of corticosteriods based on this roentgenographic pattern is stressed.

PMID- 7631213
TI  - A trial of labor complicated by uterine rupture following amnioinfusion.
AB  - Amnioinfusion has become accepted in the management of intrapartum cord
      compression, meconium-stained fluid, and oligohydramnios. Limited experience
      exists regarding amnioinfusion in patients undergoing a trial of labor after
      cesarean section and its potential complications. We report a case of trial of
      labor in which uterine rupture occurred following intrapartum amnioinfusion. This
      case demonstrates the need for careful attention to amnioinfusion volumes and
      administration in patients with a previous cesarean section.

PMID- 7631214
TI  - Herniation of the urinary bladder: a complication of traumatic pubic symphysis
      diastasis.
AB  - Bladder rupture and urethral disruption are relatively common injuries associated
      with pelvic trauma; however, bladder herniation into a public symphysis diastasis
      is an unusual sequelae of pelvic trauma. We report a case of anterior bladder
      wall herniation into a traumatic pubic diastasis and review the literature.
      Recommendations focusing on avoiding possible urinary bladder complications
      associated with closed reduction and external fixation of the diastasis are
      offered.

PMID- 7631215
TI  - Central pontine myelinolysis in a patient with bulimia.
AB  - Central pontine myelinolysis is classically described in alcoholics or other
      malnourished individuals after correction of severe hyponatremia. A patient with
      bulimia developed central pontine myelinolysis after correction of severe
      hyponatremia and hypokalemia. Early symptoms of abnormal affect and dystonia made
      initial diagnosis elusive. The spectrum of neurologic signs and possible causes
      of central pontine myelinolysis are discussed. A conservative approach to
      treatment of hyponatremia is advocated.

PMID- 7631216
TI  - Disseminated toxoplasmosis as a cause of diarrhea.
AB  - Disseminated toxoplasmosis in patients with acquired immunodeficiency syndrome is
      often a central nervous system disease but may be seen as myocarditis or
      pneumonitis. Toxoplasmic colitis is a rarity. We report a case of toxoplasma
      colitis in a patient with diarrhea and hypokalemia. The microorganisms were
      identified in the colonic mucosa on H&E sections and confirmed by
      immunoperoxidase study.

PMID- 7631217
TI  - Primary psoas abscess due to methicillin-resistant Staphylococcus aureus
      concurrent with septic arthritis of the hip joint.
AB  - We report an unusual case of a primary psoas abscess due to community acquired
      methicillin-resistant Staphylococcus aureus in an immunocompetent man. The course
      of the disease was indolent, expressed as septic arthritis of the hip joint. When
      the diagnosis was made, 3 months after symptoms began, the patient was treated by
      surgical evacuation of the abscess and appropriate antibiotics. Full recovery and
      return to his usual activity followed total hip replacement.

PMID- 7631218
TI  - Dermatomyositis: remission induced with combined oral cyclosporine and high-dose
      intravenous immune globulin.
AB  - Dermatomyositis is an uncommon idiopathic chronic inflammatory disorder. Oral
      corticosteroids are the treatment of choice. A few patients become resistant to
      steroids. We describe two patients who, after failure to respond to oral and high
      dose intravenous corticosteroids, received a combination of oral cyclosporine and
      high-dose intravenous immune globulin, with apparent remission. The first patient
      was a 6-year-old girl with recurrent disease and vasculitis, despite prednisone
      therapy and normal muscle enzyme levels. The response was remarkable within 3
      weeks of therapy. The second patient was a 30-year-old woman with progressive
      disease and secondary respiratory failure despite oral prednisone and
      methotrexate therapy. The response to treatment was optimal within 4 weeks. She
      received maintenance low-dose cyclosporine and a tapering dose of prednisone. The
      combination of high-dose immune globulin and cyclosporine can be useful and safe
      in the management of steroid-resistant dermatomyositis.

PMID- 7631219
TI  - Positional compression of vertebral artery shown by magnetic resonance
      angiography.
AB  - This report of a woman with positional dizziness is apparently the first to
      describe position-dependent vertebral artery compression shown by magnetic
      resonance angiography. This noninvasive technique may be helpful in the
      differential diagnosis of positional dizziness.

PMID- 7631220
TI  - Primary angiosarcoma of the spleen: a case report and review of the literature.
AB  - We describe a 47-year-old man with shoulder pain, multiple bony lesions, and a 1
      cm lesion in the spleen. T-1 facetectomy revealed a poorly differentiated
      malignant neoplasm. Several months after chemotherapy, multiple splenic lesions
      were found by computed tomography and liver-spleen scan. A splenectomy showed a
      malignant spindle-cell neoplasm forming irregular vascular spaces. Tumor cells
      were positive for factor VIII-related antigen and vimentin. This patient died of
      extensive metastases from this primary angiosarcoma of the spleen. Splenic
      angiosarcoma is a rare neoplasm that often has a cryptic presentation and a
      dismal prognosis.

PMID- 7631221
TI  - Dialysis-related amyloidosis manifested as masses in the buttocks.
AB  - A 40-year-old man had enlarging painful gluteal masses that developed after 17
      years of hemodialysis. Pathologic examination revealed extensive deposition of
      beta 2-microglobulin amyloid. A bladder biopsy done during evaluation for
      possible transplantation also showed amyloid deposits. This constellation of
      findings has not been reported in a patient with beta 2-microglobulin
      amyloidosis. Patients with dialysis-related amyloidosis should be carefully
      assessed for systemic involvement. Renal transplantation may prevent further
      amyloid deposition and provide relief of pain.

PMID- 7631222
TI  - Septicemic shock from urinary tract infection caused by Staphylococcus
      epidermidis.
AB  - Staphylococcus epidermidis septicemia from a urinary source is rare. Two male
      patients had septicemic shock caused by S epidermidis urinary tract infection.
      Both patients had recently had indwelling urethral catheterization during severe
      illness. Bacteremia due to S epidermidis may be life-threatening. Although most
      cases of S epidermidis bacteremia are associated with infected intravascular
      devices, other portals of entry should be considered in a debilitated patient.

PMID- 7631223
TI  - Eosinophilic pleural effusion associated with valproic acid administration.
AB  - A case of eosinophilic pleural effusion with peripheral blood eosinophilia is
      presented. No cause of the pleural effusion was found, but on cessation of
      valproic acid therapy, both the pleural effusion and eosinophilia resolved.
      Valproic acid should be added to the list of drugs associated with pleural fluid
      eosinophilia.

PMID- 7631224
TI  - Emerging drug-resistant bacteria: the wake-up call has come.

PMID- 7631225
TI  - Thrombotic thrombocytopenic purpura and HIV infection.

PMID- 7631226
TI  - Medicinal arsenic poisoning: 27-year follow-up.

PMID- 7631227
TI  - Diagnosing angiotropic large cell lymphoma.

PMID- 7631228
TI  - Hiccups due to gastroesophageal reflux.

PMID- 7631229
TI  - Transcranial magnetic stimulation of the motor cortex in cervical spondylosis and
      spinal canal stenosis.
AB  - STUDY DESIGN: This study investigated the clinical usefulness of motor evoked
      potentials and a silent period after motor evoked potentials produced by
      transcranial magnetic stimulation of the brain. OBJECTIVE: The results were
      correlated with the clinical state of the patients with myelopathy, whereas no
      abnormality of the conduction time was observed in the patients with spinal canal
      stenosis. SUMMARY OF BACKGROUND DATA: Magnetic stimulation has been widely used
      for examination of the descending excitatory motor pathways in the central
      nervous system, but little attention has been paid to cervical spondylosis and
      spinal canal stenosis. METHODS: Motor evoked potentials were examined in 35
      normal subjects, 67 patients with cervical spondylotic myelopathy, and 24
      patients with spinal canal stenosis. Motor evoked potentials were evoked by
      transcranial brain stimulation during relaxation and during maximum voluntary
      contraction of the target muscle. RESULTS: The central motor conduction time was
      found to correlate with the clinical state of the myelopathy patients, whereas no
      abnormality of the conduction time was observed in the patients with spinal canal
      stenosis. During maximum voluntary contraction of the target muscle, a silent
      period was always observed after the motor evoked potentials in the normal
      subjects, and its duration was markedly shortened in the myelopathy patients.
      CONCLUSIONS: In cervical myelopathy patients, the central motor conduction time
      was correlated with clinical evaluation and the silent period was significantly
      shortened. These findings about duration of the central motor conduction time and
      the silent period might be a useful parameter of spinal pathology.

PMID- 7631230
TI  - Is camptocormia a primary muscular disease?
AB  - STUDY DESIGN: This study analyzed computed tomographic scans, magnetic resonance
      images, and biopsies of the paravertebral muscles of patients with camptocormia
      and age-matched patients with lumbar interapophyseal osteoarthritis or lumbar
      vertebral stenosis. OBJECTIVES: To define the muscular lesions and clarify their
      nature in this particular disorder. SUMMARY OF BACKGROUND DATA: Progressive
      lumbar kyphosis or camptocormia, a rare disease of the elderly characterized by
      inability to immobilize the lumbar spine in relation to the pelvis appears to be
      a result of weakness of the paraspinal muscles. The features presented by these
      patients do not correspond to any myopathy previously described. METHODS: Twenty
      seven patients (5 men and 22 women) mean age 69 years, with camptocormia were
      compared to fifteen age-matched patients without camptocormia but with posterior
      interapophyseal osteoarthritis and to nine elderly patients operated for
      narrowing of lumbar canal. Computed tomographic scans, magnetic resonance images,
      light microscopy, histochemistry, and electron microscopy of paraspinal muscles
      were obtained in both groups. RESULTS: In patients with camptocormia, computed
      tomographic scans and magnetic resonance imaging showed heterogeneous appearance
      of the spinal muscles with areas of low density. These features were distinct
      from those of patients with interapophyseal osteoarthritis and were similar to
      the features described in primary muscular dystrophies. The main microscopic
      change in camptocormia was the increase of fibrous tissue, frequently with a
      lobular pattern, not seen in osteoarthritic patients. Familial history of the
      disorder was frequent (20 out of the 27 patients). CONCLUSION: Camptocormia,
      disappearing in the recumbent position, is thus very probably linked to muscle
      involvement. That there is often a family history of such disorder is in favor of
      a genetically transmitted condition. Magnetic resonance images and computed
      tomographic scan appearance seems to be in favor of primary muscular disease,
      restricted to the spinal muscles.

PMID- 7631231
TI  - Measuring the functional status of patients with low back pain. Assessment of the
      quality of four disease-specific questionnaires.
AB  - STUDY DESIGN: This study was a literature review of the quality of four disease
      specific functional status questionnaires for patients with low back pain:
      Oswestry; Million; Roland; and Waddell disability questionnaire. OBJECTIVES: The
      questionnaires were evaluated in terms of general description, scale structure,
      reliability, validity, responsiveness, and clinical research applications.
      SUMMARY OF BACKGROUND DATA: Functional status is an outcome of great interest for
      clinical trials of low back pain. METHODS: A computer-aided search was conducted
      of articles published between 1981 and 1993 and references given in selected
      relevant publications. Articles were selected if at least one of the four
      functional status questionnaires was used or if the authors gave relevant
      information about the methodology of these questionnaires. RESULTS: There was not
      enough information available about the criteria of item selection used for the
      development of the questionnaires. The test-retest reproducibility of the
      questionnaires seemed satisfactory. The Oswestry and Roland disability
      questionnaires have been used and evaluated more frequently than the Million and
      Waddell. Therefore, we can be more certain about the validity and responsiveness
      of the former pair of questionnaires. CONCLUSION: In the absence of a gold
      standard, direct comparisons of evaluative functional status questionnaires in a
      single patient group are needed. Through direct comparisons, comparative validity
      and responsiveness can be assessed. Functional status measures are not currently
      used in many settings in which they would be valuable. It is important to
      encourage their wider use in clinical trials. Additional research is needed to
      compare and improve the existing questionnaires.

PMID- 7631232
TI  - Observer variability in the assessment of disc degeneration on magnetic resonance
      images of the lumbar and thoracic spine.
AB  - STUDY DESIGN: Intraobserver and interobserver reproducibility study. OBJECTIVE:
      This study investigates the variability in the interpretation of degenerative
      disc findings using magnetic resonance imaging. SUMMARY OF BACKGROUND DATA:
      Magnetic resonance imaging has been used for years in clinical diagnostics,
      primarily to investigate disc herniation and spinal stenosis. Less attention has
      been paid to other disc findings and their assessment reliability. METHODS: Three
      independent readers evaluated magnetic resonance images of the lumbar and the
      lower and middle thoracic spines of 122 subjects by grading 12 aspects of the
      intervertebral discs and adjacent endplates using written definitions and example
      images. Images of 20 subjects were reevaluated for the assessment of
      intraobserver agreement. RESULTS: Agreement was highest in the lower lumbar and
      poorest in the middle thoracic spine. Intraobserver agreement was generally fair
      to excellent for almost all variables in the lumbar and lower thoracic spine
      (most intraclass correlation and kappa coefficients for these regions were above
      0.70). Interobserver agreement was notably lower than intraobserver agreement,
      except for osteophytes and endplate defects in some regions. CONCLUSIONS:
      Intraobserver agreement in the evaluation of disc degeneration was at an
      acceptable level, in general, in the lumbar and lower thoracic spine. However,
      assessments were substantially more variable between readers, which limits
      comparisons of evaluations between different readers.

PMID- 7631233
TI  - A database for estimating normal spinal motion derived from noninvasive
      measurements.
AB  - STUDY DESIGN: A database for estimated normal spinal motion was derived using a
      noninvasive, high-resolution, computer-aided system, which tracks the motion of
      skin markers strategically placed on the spine. Forty normal subjects, selected
      from hundreds of possible subjects according to rigorous inclusion/exclusion
      criteria, were tested on the system. OBJECTIVES: Patterns of estimated spinal
      motion were analyzed as a function of load, age, and sex, confirming a
      correlation between the movement of spinal segments and the motion of skin
      markers. SUMMARY OF BACKGROUND DATA: The Workers Compensation Board of Quebec
      funded and supervised the experiments necessary to establish a normative
      reference database for a high-resolution motion analysis system that permits a
      noninvasive assessment of spinal function. A previous study examined the
      correlation between the movements of the skin markers and the underlying bony
      structures for trunk flexion. Skin movement cannot be random and contains
      information characterizing both the spine and its surrounding soft tissues.
      METHODS: A noninvasive dynamic imaging system was used to measure normal spinal
      function under free movement. A high-resolution three-dimensional camera system
      collected basic kinematic data from strategically placed skin markers over the
      lumbar spine while the activity of paraspinal muscles was being recorded with
      surface electromyography. The measurements were analyzed for consistent, specific
      patterns recognizable as normal lumbar spine skin motion and reflecting normal
      lumbar spine function. A comparison was made with previous radiographic studies
      to confirm the correlation between the motion of skin markers and lumbar spine
      function. RESULTS: Lumbar skin marker motion patterns in normal subjects were
      consistent and varied little with load; gender had no effect except in the
      initial phase of a movement. There was less mobility but similar coordination in
      older subjects. No inconsistencies with previous radiologic investigations were
      found for sagittal and lateral plane movement.

PMID- 7631234
TI  - Sacroiliac kinematics for reciprocal straddle positions.
AB  - STUDY DESIGN: A descriptive and correlation approach was used to assess joint
      motion. OBJECTIVES: Magnitudes and directions of sacroiliac motion were examined
      from three different upright postural conditions. SUMMARY OF BACKGROUND DATA:
      Evidence and clinical views suggest that sacroiliac motion available in the
      normal case is extremely small to nonexistent. METHODS: Systems for standardizing
      the three postures and the Metrecom skeletal analysis system (Metrecom, Faro
      Technologies, Inc., Lake Mary, FL) for acquiring coordinate data for selected
      skeletal landmarks. RESULTS: The complete sacroiliac oblique-sagittal motion that
      occurred between the right forward and left forward stride positions was 9
      degrees (SD 6.5). The composite oblique-transverse motion was 5 degrees (SD 3.9).
      The motions in each plane were significantly different from zero. A joint
      mobility relationship existed between the hip and sacroiliac joints. CONCLUSION:
      The results demonstrate that substantial angular motion is possible at the
      sacroiliac joints.

PMID- 7631235
TI  - Iliac crest bone graft harvest donor site morbidity. A statistical evaluation.
AB  - STUDY DESIGN: This study analyzed the cause, rate, and risk factors of iliac
      crest bone graft donor site morbidity. OBJECTIVES: All complications or problems,
      no matter how small, were sought to develop strategies of prevention. SUMMARY OF
      BACKGROUND DATA: A wide range of major, 0.76% (Keller et al) to 25% (Summers et
      al) and minor complications, 9.4% (Keller et al) to 24% (Summers et al) has been
      reported. METHODS: A consecutive series of 261 patients, whose bone graft harvest
      was done by one surgeon, was studied by chart review and a mail survey that was
      not conducted by the operating surgeon. The survey presented specific open-ended
      questions designed to uncover any complication/problem, no matter how small.
      Complications then were categorized as major or minor and subcategorized as acute
      or chronic. Statistical analysis was done using chi-squared and multiple
      logistical regression. RESULTS: None of the 261 patients had a severe
      perioperative complication--e.g., superior gluteal artery injury, sciatic nerve
      injury, or deep wound infection. None of the 225 patients with long term follow
      up (average, 66 months; range, 32-105 months) had a severe late complication-
      e.g., donor site herniation, meralgia paresthetica, pelvic instability, or
      fracture. Of the 180 patients meeting the qualifications for statistical
      analysis, major complications occurred in 18 (10%), only three of which affected
      function (pain). Minor complications occurred in 70 (39%). CONCLUSIONS: The
      results indicated that severe complications from iliac crest bone graft harvest
      can be avoided and major complications affecting functioning are uncommon, but
      minor complications are common. The findings suggest that procedural refinements
      of limiting subcutaneous dissection and providing layered tension-free incision
      closure may improve results.

PMID- 7631236
TI  - Effects of the combined VDS-Zielke and Harrington operation on the frontal rib
      cage deformity of double major curves in idiopathic scoliosis.
AB  - STUDY DESIGN: This study analyzed the changes in the frontal plane of the
      deformed lower rib cage and the scoliosis-related alterations on the spine in
      patients with double major curve-pattern idiopathic scoliosis. OBJECTIVES: The
      results obtained preoperatively, after the Zielke operation, postoperatively
      after the Harrington instrumentation, and at the follow-up evaluation were
      compared to investigate which changes of the elements of the rib cage deformity
      are caused by each of the two instrumentations. SUMMARY OF BACKGROUND DATA:
      Previously, Wojcik reported on the effects of a Zielke operation on the lower rib
      in mild S-shaped idiopathic scoliosis. No previous data exist regarding the lower
      rib cage deformities in severe idiopathic double major-pattern scoliosis and
      their changes after combined VDS-Zielke and Harrington instrumentation. METHODS:
      Fifteen patients who underwent the staged Zielke operation followed by Harrington
      rod instrumentation were followed-up for an average period of 31.1 months. The
      methods used in our study included Cobb angle and a segmental analysis (T7-T12)
      of each of convex and concave rib-vertebra angles, rib-vertebra angle
      differences, vertebral rotation, and vertebral tilt. RESULTS: In this series, the
      apical convex ribs showed an increased droop preoperatively compared with the
      concave apical ribs. The VDS-Zielke operation corrected the lumbar scoliosis in
      an average of 63% of patients, whereas the thoracic scoliosis showed an immediate
      spontaneous correction of 30%. The VDS-Zielke operation also produced a
      significant correlation of the scoliosis-related vertebral tilt (T10-T12),
      derotated the lumbar vertebrae and the T12 vertebra significantly, elevated the
      "mobile" concave ribs, and increased the droop of the lower (T11, T12) "mobile"
      convex ribs. The Harrington instrumentation did not change the vertebral
      rotation, the vertebral tilt, the convex rib-vertebra angle, or the L4 obliquity,
      but significantly changed the apical concave rib-vertebra angle. The combined
      Zielke-Harrington instrumentation reduced the thoracic kyphosis and the
      thoracolumbar junction-kyphosis significantly, whereas the lumbar lordosis
      remained practically unchanged. CONCLUSIONS: Only the anterior VDS-Zielke
      instrumentation significantly corrects severe spinal deformities, elevates the
      three lower ribs on the concavity, and increases the droop of the two lower ribs
      on the convexity in the severe idiopathic double major curve-pattern scoliosis
      combined operated (Zielke-Harrington). Therefore, the Harrington instrumentation
      should have only limited use in cosmetic scoliosis surgery and should be replaced
      with posterior multi-hook instrumentation with a derotation effect.

PMID- 7631237
TI  - Evaluation of intrapedicular screw position using intraoperative evoked
      electromyography.
AB  - STUDY DESIGN: This study analyzed the parameters needed for electrical
      stimulation of vertebral pedicle drill bits and screws. OBJECTIVES: The
      feasibility of using electrically evoked electromyography was studied. SUMMARY OF
      BACKGROUND DATA: Considerable potential for damage of adjacent nerve roots with
      incorrectly placed bits and screws exists with pedicular fixation of the lumbar
      spine. METHODS: Ninety-five drill bits, one hundred forty-four screws, and thirty
      four exposed nerve roots were electrically stimulated in thirty-six patients.
      Simultaneous evoked electromyographic activity was recorded from four muscle
      groups in each lower extremity during partial neuromuscular blockade. RESULTS: A
      constant current threshold of 6 mA or less correlated with misplaced drill bits
      and screws that broached the cortex. Evoked electromyography was 93% sensitive
      whereas radiography was only 63% sensitive to detecting bits and screws that had
      broached the cortex. CONCLUSIONS: Evoked electromyography is a valuable sensitive
      adjunct to radiographic examination of pedicle drill bit and screw placement.

PMID- 7631238
TI  - Cord compression caused by multiple disc herniations and intraspinal cyst in
      Scheuermann's disease.
AB  - STUDY DESIGN: The design for this article is a case report. OBJECTIVES: Reported
      is the case of a patient with Scheuermann's disease who experienced spastic
      paraparesis caused by multilevel disc herniations and intraspinal meningeal cyst
      occurring together. SUMMARY OF BACKGROUND DATA: Although Scheuermann's disease is
      associated with disc degeneration and calcification, multilevel disc herniations
      causing neurologic deficit is exceedingly rare. METHODS: A patient diagnosed with
      Scheuermann's disease was evaluated by laboratory tests and radiographs because
      of paresthesin in bilateral lower extremities. RESULTS: Evaluation revealed a
      "cyst" that was separated from the proper subarachnoid space and a disc
      herniation. CONCLUSIONS: Intraspinal cyst and multilevel disc herniations could
      coexist in Scheuermann's disease. Both could contribute to cord compression.
      Drainage of the cyst, anterior decompression of the disc herniations, and
      interbody fusion to stabilize the diseased segments produced good results after 2
      years.

PMID- 7631239
TI  - Extension-distraction fracture of the first lumbar vertebra.
AB  - STUDY DESIGN: This is a case report of an unusual fracture of the first lumbar
      vertebra in which the mechanism of injury appears to have been an extension
      distraction force. The case report elucidates the patient's initial presentation
      at the time of injury, the treatment instituted, and follow-up revealing
      satisfactory healing of the fracture 18 months later. OBJECTIVES: The case is
      reported to illustrate an usual injury that had not been previously reported.
      SUMMARY OF BACKGROUND DATA: History, physical examination, and imaging studies
      from the time of injury, after initial treatment, and at final follow-up are
      presented. METHODS: A case report is presented in which a fall subjected a
      patient's stiff, osteopenic spine to an extension moment, resulting in tension
      failure of the bony elements of the anterior and middle columns. Plain
      radiographs, tomograms, and a magnetic resonance image detail the injury pattern;
      plain radiographs are presented as follow-up images. RESULTS: Nonoperative
      treatment in this case led to a satisfactory outcome at 18 months follow-up.
      CONCLUSION: An unusual extension-distraction fracture of the spine is presented,
      which, in this case, was satisfactorily treated nonoperatively.

PMID- 7631240
TI  - Spine update. Degenerative lumbar spondylolisthesis.
AB  - Degenerative lumbar spondylolisthesis associated with spinal stenosis is a common
      condition of the aging spine. This article presents a detailed description of the
      pathophysiology, clinical presentation, and nonoperative and operative
      intervention of this condition.

PMID- 7631241
TI  - Lewis Albert Sayre.
AB  - Lewis Albert Sayre (1820-1900) was an American pioneer in the field of orthopedic
      surgery, and medicine in general. In addition to much work on spinal and other
      deformities, Sayre was a founder of what later became the New York University
      Medical School, where he headed the first department of orthopedics in the United
      States. Sayre also was a charter member of the American Medical Association and
      served as its vice president and later as president. He was instrumental in
      developing the Journal of the American Medical Association, and his extensive
      work as Resident Physician of New York City led to improvements in sanitation,
      vaccination, and quarantine for smallpox and cholera.

PMID- 7631242
TI  - Controversy. Low back school. Education or exercise?
AB  - Few interventions have conclusively changed the natural history of low back pain
      with respect to recovery once an episode has begun, or have prevented future
      recurrence. Variations of the low back school, an educational approach, have
      become increasingly popular but their efficacy remains controversial. Dr. Hall is
      emphatic that patient education is a less than perfect but nonetheless an
      important approach. Dr. Hadler believes that these programs re-enforce the
      misconception that low back pain is an injury rather than a commonly occurring
      life event, such as the flu, and should be handled but not overtreated. He offers
      a more tempered opinion.

PMID- 7631243
TI  - Three-dimensional magnetic resonance techniques for evaluating the cervical
      spine.
AB  - The general technique of three-dimensional magnetic resonance imaging is briefly
      described, as is a variety of specific three-dimensional sequences useful in the
      evaluation of spinal disease, particularly related to degenerative disc disease.
      Advantages of three-dimensional imaging include an increase in signal-to-noise
      ratio, thin contiguous slices, more accurate slice thickness, and a reduction in
      susceptibility artifacts. Computer post-processing allows reformatting of the
      data along any desired imaging plane, with minimal degradation in image quality.

PMID- 7631244
TI  - Regional variation in tensile properties and biomechanical composition of the
      human lumbar anulus fibrosus.

PMID- 7631245
TI  - Immunoglobulin E antibodies to papaya proteinases and their relevance to
      chemonucleolysis.
AB  - STUDY DESIGN: Levels of four papaya cysteine proteinases were determined in
      Chymodiactin, a pharmaceutical preparation of chymopapain (EC 3.4.22.6) used in
      chemonucleolysis for the treatment of sciatica. Twelve sera known to contain
      immunoglobulin E antibodies to Chymodiactin were assayed for immunoglobulin E
      antibodies to these enzymes. OBJECTIVES: The goal of the study was to determine
      what contribution each of the four proteinases makes to the allergic response
      that occasionally occurs during injection of a damaged intervertebral disc with
      chymopapain preparations. SUMMARY OF BACKGROUND DATA: The occurrence of an
      allergic reaction during chemonucleolysis implies prior sensitization to
      components of the injected enzyme solution. The latex of the unripe fruit of the
      papaya plant Carica papaya, from which chymopapain is purified, contains another
      three immunologically distinct cysteine proteinases: 1) caricain (EC 3.4.22.30),
      2) glycyl endopeptidase (EC 3.4.22.25), and 3) papain (EC 3.4.22.2). METHODS: A
      dot-blot immunoassay was developed to quantify each enzyme in Chymodiactin. Total
      serum immunoglobulin E levels and specific immunoglobulin E antibody levels to
      each of the four papaya cysteine proteinases were assayed by an enzyme-linked
      immunoassay in 12 sera containing immunoglobulin E antibodies to Chymodiactin.
      RESULTS: Chymodiactin contained 70% chymopapain, 20% caricain, 4% glycyl
      endopeptidase, and 0.1% papain. Immunoglobulin E antibodies to all four
      proteinases were found in most of the 12 sera, but in varying proportions.
      Antibodies to glycyl endopeptidase were predominant in eight sera, and the mean
      amounts of immunoglobulin E directed against each protein were: glycyl
      endopeptidase, 4.21 IU/ml; caricain, 2.9 IU/ml; chymopapain, 1.97 IU/ml; and
      papain, 1.39 IU/ml. Total serum immunoglobulin E levels showed little correlation
      with immunoglobulin E responses to Chymodiactin. CONCLUSIONS: The results
      suggested that removal of glycyl endopeptidase and caricain from pharmaceutical
      preparations of chymopapain may help reduce the incidence of allergic reactions
      during chemonucleolysis.

PMID- 7631246
TI  - The use of expanded polytetrafluoroethylene as an interpositional membrane after
      lumbar laminectomy.
AB  - STUDY DESIGN: Prevention of post-laminectomy membrane formation was evaluated in
      a canine model. Fat graft, Silastic sheeting and expanded polytetrafluoroethylene
      were compared with nonimplanted control sites. OBJECTIVES: The development of an
      effective barrier to peridural scar invasion is of major importance in optimizing
      results after lumbar laminectomy. SUMMARY OF BACKGROUND DATA: Postoperative
      peridural fibrosis represents a normal biologic response after lumbar spinal
      surgery. A variety of biologic and nonbiologic interpositional materials have
      been studied. Expanded polytetrafluoroethylene has been shown to limit scar
      adhesion in the pericardium and peritoneum and has not been studied previously as
      a postlaminectomy interpositional membrane. METHODS: Eleven adult female cross
      bred hounds underwent multilevel standardized laminotomies. Three materials--fat
      graft, Silastic sheeting, and expanded polytetrafluoroethylene--were compared
      with nonimplanted controls. The animals were killed 12 weeks after surgery and
      were evaluated histologically and using gadolinium-enhanced magnetic resonance
      imaging. RESULT: The magnetic resonance imaging studies were inconclusive in
      assessing peridural scar extension or identifying the implanted membranes.
      Histology revealed dense scar tissue at all control sites and replacement of all
      fat grafts by scar. Scar density was significantly less for the expanded
      polytetrafluoroethylene membrane surgical sites than for the control, fat graft,
      and Silastic sheeting sites. CONCLUSIONS: Expanded polytetrafluoroethylene
      membrane is biocompatible, maintains its structural integrity, and is impervious
      to fibrous ingrowth. These findings support further investigation of expanded
      polytetrafluoroethylene membrane as an interpositional material to prevent post
      laminectomy peridural fibrosis.

PMID- 7631247
TI  - Muscle activity and low back loads under external shear and compressive loading.
AB  - STUDY DESIGN: This study analyzed anatomic and neural control characteristics of
      the trunk musculature. Subjects were exposed to external shear and compressive
      loads with equivalent moments to evaluate activation patterns and loading on the
      low back. OBJECTIVES: The migration of activity between the thoracic and lumbar
      erector spinae muscle groups was examined to determine whether the motor control
      system chooses to minimize joint loading by recognizing differences in moment,
      compression, and shear support requirements and assigning muscle activation in
      the most appropriate way. SUMMARY OF BACKGROUND DATA: Loads were applied either
      parallel or perpendicular to the low back to create compressive or shear forces.
      No previous study has attempted to isolate the response of the trunk musculature
      with the type of external load. METHODS: Eleven male subjects isometrically held
      an external load that was altered to create either a compressive or an anterior
      shear load on the low back but with equal extensor (reaction) moments (experiment
      1). In a second experiment four men repeated the task with an increased range of
      applied loads (5-25 kg) together with measurements of intra-abdominal pressure.
      RESULTS: The tasks with a compressive external load resulted in significantly
      higher levels of activation for all seven electromyographic channels recorded.
      Intraabdominal pressure, compressive and shear joint forces were all higher in
      the compression loading method when equal loads and low back moments were
      compared. CONCLUSIONS: It was concluded that the motor control system does not
      arrange muscle activation levels in a way to minimize lumbar spinal loading at
      least for the relatively low levels of this study. Biomechanical models that use
      the objective criterion of minimum joint load may not be representative of the
      motor control system, at least in the low back.

PMID- 7631248
TI  - Stiffening effects of cortical bone on vertebral cancellous bone in situ.
AB  - STUDY DESIGN: This study tested a theory about vertebral cancellous bone
      stiffness by performing experimental tests and comparing the results with the
      theoretical predictions. OBJECTIVES: To test experimentally a theoretical
      prediction that vertebral cancellous bone appears stiffer than would be expected
      from isolated tests because of the constraining effects of the cortical bone, to
      measure the magnitude of this strengthening effect and its dependency on tissue
      composition and density. SUMMARY OF BACKGROUND DATA: Vertebral bodies are
      composed mainly of cancellous bone surrounded by a thin shell of much stronger
      cortical bone. Little is known of the ways in which these two materials function
      synergistically to produce strong but light structures and why sometimes
      extensive damage to the cancellous bone has apparently little outward effect on
      vertebral body strength. METHODS: Cancellous bone from 45 lumbar vertebrae from a
      homogeneous group of pigs was tested in compression both in situ in the vertebral
      body and as an excised cylinder. The density and composition of the bone were
      then measured and correlation tested with both of the stiffness measurements.
      RESULTS: The cancellous bone in situ appears much stiffer than when isolated by a
      factor of about 4 (range, 1.6-12). No correlation was found between stiffness,
      either in situ or in isolation, and density, although density is predicted
      entirely by the volume fractions of water, organic, and mineral phases.
      CONCLUSIONS: Combining low density cancellous bone with stiffer, more dense
      cortical bone leads to a lightweight structure that is much stronger than might
      be expected from the isolated properties of its components.

PMID- 7631249
TI  - Subungual melanoma.
AB  - Twenty (1.5%) of 1,350 patients with malignant melanoma treated during a 17-year
      period had their primary lesion in the nail bed. The thumb (5 patients) and big
      toe (7) were the most commonly involved digits. Mean delay before diagnosis was
      1.4 years. Thirteen patients were black and 7 white. Eight patients (40%) were
      initially misdiagnosed as having traumatic, infective or benign lesions. Four
      patients presented with recurrent local disease after inappropriate nail excision
      or inadequate nail biopsy, while 2 patients had regional nodal spread and 2 had
      systemic metastases. Mean Breslow depth was 5.7 mm. The histogenetic subtypes
      were acral lentiginous melanoma (12 patients) and nodular melanoma (4 patients);
      4 lesions were unclassifiable. All patients underwent amputation of the involved
      digit and 12 required node dissection (therapeutic in 11, prophylactic in 1).
      Five patients (25%) are alive (mean 52 months, range 29-99 months); 4 are disease
      free and 1 has brain metastases. Overall median survival was 32 months with a 26%
      5-year survival rate. Delayed diagnosis and advanced disease at presentation
      contributed to the poor prognosis in nail bed melanoma.

PMID- 7631250
TI  - Leiomyosarcoma of the breast. A case report.
AB  - A case of primary leiomyosarcoma of the breast in a 35-year-old woman is
      presented. The condition is rare, only 11 cases of primary leiomyosarcoma of the
      breast having been reported previously. The clinical and pathological features
      are reviewed.

PMID- 7631251
TI  - Gastroduodenal intussusception of a stromal gastric tumour.
AB  - An elderly patient presented with intermittent vomiting. The cause was a gastric
      tumour causing gastroduodenal intussusception. On excision and histological
      examination this was found to be a stromal tumour of uncertain malignant
      potential ('STUMP').

PMID- 7631252
TI  - Ruptured abdominal aortic aneurysms--prognostic indicators and complications
      affecting mortality. A local experience.
AB  - Although elective abdominal aortic aneurysm (AAA) repair can be done with a less
      than 5% mortality rate, ruptured AAAs have a 32-85% mortality rate. The aims of
      this study were: (i) to identify prognostic factors affecting mortality; (ii) to
      identify and assess the impact of postoperative complications on mortality; and
      (iii) to try to identify a subgroup of patients who would not benefit from
      surgery. The records of 54 patients presenting with ruptured AAAs were reviewed;
      49 of these patients were operated on, 43 of them males and 6 females (mean age
      67 years). The operative mortality rate was 44%, most patients who died doing so
      in the intensive care unit. In 14 cases AAA was diagnosed before rupture--6 of
      these patients died. Factors that had a significant effect on mortality were: (i)
      associated ischaemic heart disease--83% of these patients died postoperatively;
      (ii) the degree of shock on admission--66% of patients with a blood pressure on
      admission of 85 mmHg or less died; and (iii) the number of postoperative
      complications per patients--those with 2 or more complications had an 83%
      mortality rate. Factors that did not correlate statistically with mortality were
      age, time interval to surgery, volume and composition of intra-operative fluid
      therapy, and length of surgery. The most important correctable error was failure
      to operate electively. From the factors assessed it was not possible clearly to
      identify a subgroup of patients in this study who should have been excluded from
      surgery.

PMID- 7631253
TI  - Chylous ascites following abdominal aortic surgery.
AB  - Chylous ascites is an extremely rare complication of abdominal aortic surgery. A
      case with a successful outcome is presented, followed by a review of the 17
      published cases. Chylous ascites can result in nutritional imbalance,
      immunological deficit and respiratory dysfunction. Paracentesis confirms the
      diagnosis and provides symptomatic relief. Conservative management, beginning
      with a low-fat diet and medium-chain triglyceride (MCT) supplementation, is
      recommended, changing to total parenteral nutrition if unsuccessful. Failure of
      non-operative treatment may necessitate the need for laparotomy and ligation of
      leaking lymphatics or peritoneovenous shunting.

PMID- 7631254
TI  - Aberrant common hepatic artery aneurysm. A case report.
AB  - A 45-year-old white woman was found on selective superior mesenteric artery
      angiography to have an aneurysm arising in an aberrant hepatic artery. The
      aberrant hepatic artery originated from the superior mesenteric artery, and was
      the only artery supplying the liver. The aneurysm was excised and continuity of
      the aberrant artery was restored by insertion of a short segment of autogenous
      long saphenous vein.

PMID- 7631255
TI  - Surgical complications of radical cystectomy in a teaching hospital.
AB  - We reviewed the surgical complications in 112 consecutive patients who had
      undergone radical cystectomy for bladder cancer at Tygerberg Hospital between
      1978 and 1989. The cystectomies were performed by a total of 16 surgeons, of whom
      1 (A) performed 30 and assisted at 2, 1 (B) performed 26 and assisted at 4, 2 (C
      + D) performed 27 and assisted at 16, and 12 (E-P) performed 29 and assisted at
      46. Pre-operative radiotherapy was given in 37% of cases and intravesical
      chemotherapy in 25%. Major coexisting medical problems were present in 60%. The
      overall peri-operative mortality rate was 11%, but the rate was significantly
      lower (3%) in the group of patients operated on by surgeon A than in those
      operated on by surgeons E-P (21%). Major early postoperative complications
      occurred in 17% of the patients and major late complications in 25%. There were
      no significant differences between the different surgical groups in early and
      late complication rates. Peri-operative mortality and major early complications
      were significantly increased in patients aged over 71 years compared with those
      aged under 60 years. Peri-operative mortality was significantly increased in
      patients who had not received pre-operative radiotherapy compared with those who
      had done so. The presence of major coexistent medical problems did not
      significantly affect the rates of peri-operative mortality or major early or late
      surgical complications. Peri-operative mortality was lower in patients with T0-1
      tumours than in those with T2-4 tumours, but the stage did not affect the
      incidence of major early or late surgical complications.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7631256
TI  - A survey of South African endoscopic surgical practice.
AB  - To coincide with the first annual meeting of the South African Society of
      Endoscopic Surgeons (SASES), a postal survey of the endoscopic surgical practices
      of 98 registered specialist surgeons was undertaken. A response rate of 73.5% was
      achieved, and 94.5% of respondents had personally performed endoscopic surgical
      procedures. Cholecystectomy (4,557) was the most commonly performed endoscopic
      surgical procedure and was associated with a postoperative mortality rate of
      0.13% and morbidity of 3.5%. Twelve bile duct injuries were reported (0.26%). In
      descending order of frequency, other procedures reported were diagnostic
      laparoscopy (1,404), dorsal sympathectomy (412), appendicectomy (396), inguinal
      hernia repair (146), anti-reflux procedures (83) and diagnostic thoracoscopy
      (51). No postoperative deaths were recorded and complication rates varied from
      zero for diagnostic thoracoscopy to 4.8% for inguinal hernia repair and anti
      reflux procedures. The selected sample of South African surgeons canvassed
      appears to have adopted endoscopic surgical techniques with enthusiasm and with
      complication rates that compare favourably with those reported elsewhere.

PMID- 7631257
TI  - [Assessment of medical measures].
AB  - PURPOSE: Recently, the discipline Health Economics gained considerable interest.
      This interest was stimulated by the experienced limitations of resources and cost
      containment which requires the analysis of the values of treatments based on
      their relative costs and outcomes. The experiences of limited resources could
      lead to purely cost-based decisions such as favoring inexpensive services instead
      of facilitating the access to better and more useful ones. In order to decrease
      the risk of such uneconomic decisions we propose a hierarchy of assessments for
      the evaluation of clinical services. RESULTS: This hierarchy is based on the
      distinction of effectiveness and utility of medical service. Effectiveness is
      expressed in variable dimensions such as duration of sleep, concentration of
      blood sugar or diameter of a lesion. Utility is expressed by prolongation of
      survival and/or improvement of quality of life. The hierarchy suggests to assess
      the clinical utility from the patient's point of view as a first step by
      measuring the effects of the service on quantity and quality of life. In a second
      step, the clinical value of alternative medical interventions from the patient's
      point of view should be assessed by measuring the patient preference
      prospectively or the patient compliance retrospectively. Finally, as a third
      step, the economic value is assessed by comparing costs with outcomes.
      CONCLUSIONS: The suggested hierarchy should support the selection of the most
      useful services among alternative measures. In addition it should stimulate
      cooperation between the involved disciplines.

PMID- 7631258
TI  - [Periarthritis humeroscapularis (PHS). Indications, technique and outcome of
      radiotherapy].
AB  - BACKGROUND: Radiation treatment for patients with acute or subacute tendonitis or
      bursitis of the shoulder once commonplace has been mostly supplanted by
      antiinflammatory drug treatment. PATIENTS AND METHODS: 106 patients with
      clinically evident disease of PHS were treated between January 1987 and May 1991.
      73/106 patients had a continuous follow-up. 16/73 patients showed typical
      symptoms on both shoulders: therefore a total of 89 shoulders were examined in
      this investigation. A daily dose of 0.5 Gy was given for 3 times a week and a
      total dose of 3.0 Gy. After 8 weeks a second treatment course was performed. In
      follow-up the subjective (pain) and objective (limitation of abduction) symptoms
      were classified in 3 grade scales. RESULTS: A marked pain reduction and an
      improved mobility (abduction of at least 20 degrees more than before radiation)
      could be observed in 72/89 shoulders (81%). 44/89 shoulders (49%) showed an
      excellent response and were completely free of pain and impairment of motion.
      CONCLUSION: Radiotherapy of acute or subacute Periarthritis humeroscapularis is a
      very effective treatment if radiation starts within the first year of symptoms
      and if it is supported by physiotherapy.

PMID- 7631259
TI  - [Hope in radiotherapy patients with poor prognosis].
AB  - BACKGROUND: The psychological situation of patients undergoing radiotherapy has
      been investigated in a joint research project of the Department of Medical
      Psychology and the Department of Radiology of the University Clinic, Hamburg.
      This project developed interventions to support these patients psychologically.
      PATIENTS AND METHOD: Between 1990 and 1993 77 patients with final prognosis have
      been regularly seen by a psychologist during radiotherapy and some of them
      afterwards in addition. With these patients, medical doctors and relatives 763
      contacts have been documented by verbal description and analyzed, aided by a
      special computer program for qualitative analysis. This paper is concerned with
      only one topic that has emerged from the material: hope. RESULTS: Patients with
      final prognosis oscillate between hope and anxiety. Hope goes along with
      mechanisms of defence like denial and displacement which are adopted to counter
      anxiety and to protect personal integrity. There is a wide range of carriers of
      hope, including the doctor in charge and the magic healer as well. Nonstandard
      alternative therapy is often mediated by an initiative from a relative. The hopes
      of patients are not only focused on therapy but also on decent human
      responsiveness to their predicament. CONCLUSIONS: Hope is a basic emotional stand
      that is of vital importance for many patients, even when facing impending death.

PMID- 7631261
TI  - [Experience in dealing with artificial pacemaker patients during therapy with
      ionizing radiation].
AB  - BACKGROUND: During radiotherapy the pacemaker-patient is exceptionally endangered
      by ionising radiation, because a damaging impact on the pacemaker's circuit is
      possible. PATIENTS AND METHODS: Guided by experiences of long standing dealing
      with pacemaker-patients during radiotherapy in our medical centre, we demonstrate
      possibilities to accompany these patients with well coordinated interdisciplinary
      co-operation. So the possible risks by ionising radiation can be identified and
      restricted. Our investigations on explanted pacemakers will explain the influence
      on programmable pacemaker systems. Standard values for the dose of 9-MV-photons
      will be recommended. RESULTS: The radiation dose, the pacemaker system is exposed
      during radiotherapy, should be kept as small as possible by suitable methods (e.
      g. shielding, selection of radiation quality, shifting of the pacemaker system to
      a region of less doses), to ensure that the functions and the duration of life is
      not effected. Because of the different manufacturing technologies and the
      scattering of the product parameters within a homogeneous set of pacemakers we
      are not able to specify a guaranteed value for the radiation resistance.
      CONCLUSIONS: The doses of pacemaker should be as minimal as possible. The
      patient's pacemaker system has to be controlled in adequate periods, in
      particular during radiotherapy. If the accumulate dose on the pacemaker system
      exceeds 5 Gy despite of all efforts, the pacemaker should be exchanged after the
      radiotherapy.

PMID- 7631260
TI  - [Neoadjuvant radiochemotherapy in locally advanced non-small cell bronchial
      carcinoma. Initial results of a prospective multicenter study].
AB  - PURPOSE: In the last years new encouraging methods in the therapy of bronchial
      carcinoma have been elaborated. The early stages of bronchial carcinoma are still
      a domain of operative treatment. The long-term results of surgical treatment for
      locally advanced disease are considered to be unfavourable. Multimodal treatment
      concepts with simultaneous or consecutive application of radio-chemotherapy
      followed by surgical resection seem to reveal improved possibilities of therapy.
      PATIENTS AND METHODS: General treatment consists of 2 blocks of neoadjuvant
      chemotherapy with carboplatin, ifosfamide and etoposide, followed by a third
      course, consisting of carboplatin and vindesine. Simultaneously with the third
      course a hyperfractionated, accelerated radiotherapy with a single dose of 1.5 Gy
      10 times per week is applied. The total dose is 45 Gy in 3 weeks, given at least
      to the 80% isodose. After restaging, tumor resection is carried out. Patients
      without tumor are randomized for prophylactic brain irradiation. RESULTS: From
      January 1992 up to 1.10.1993 25 patients have been treated in accordance to the
      study. All tumors were locally advanced (stage IIIa and IIIb). Until 1.10.1993 4
      patients died, 2 of them certainly related to the tumor. Thirteen patients have
      been resected after neoadjuvant treatment. In 11 of these cases a R0-, and in 2
      cases a R1 resection has been carried out. Tumor cells have been found only in 5
      histologies. The hematotoxic side effects under competing RTX/CTX seemed to be
      unproblematical (RTOG/grade II). Problems occurred with 4 cases of serious
      esophagitis (RTOG/grade III to IV) and 2 cases of pneumonitis with 1 case ending
      lethally. CONCLUSION: Preliminary results of our study show the feasibility of
      multimodal treatment. A favourable 1-year survival rate after aggressive
      multimodal therapy and a high resection rate in previously unresectable patients
      could be demonstrated.

PMID- 7631262
TI  - Calcium antagonist radioprotectors do not reduce radiotherapeutic efficacy in
      three human tumor xenografts.
AB  - AIM: Calcium antagonists, which protect normal tissue as exemplified by bone
      marrow cells from radiation injury, were evaluated for radioprotection of tumor
      cells. MATERIALS AND METHODS: One Ewing's sarcoma and 2 colon carcinomas were
      grown as xenografts in immunosuppressed mice. The mice were treated with
      diltiazem, nifedipine, nimodipine and nitrendipine. The effect of whole body
      gamma-radiation on the growth of the subcutaneously implanted tumors was
      assessed. RESULTS: Growth delay or regression of the tumors in mice treated with
      the calcium antagonists prior to irradiation was not reduced as compared to only
      irradiated controls. CONCLUSION: The tested calcium antagonists, which are well
      tolerated and protect mice from death after lethal radiation, did not prevent the
      radiotherapeutic effect on 3 human tumors. This points to the possibility of
      differential radioprotection and thus to improve the therapeutic ratio in cancer
      radiotherapy.

PMID- 7631263
TI  - [Social support of radiotherapy patients in emotional stress and crisis
      situations].
AB  - PURPOSE: This study assesses the psychosocial strains imposed upon radio
      oncological patients throughout their treatment. We investigated patients'
      resources of social support and their relationship towards doctors, nursing staff
      and technical staff. PATIENTS AND METHODS: One hundred and fifty radio
      oncological follow-up patients were asked retrospectively to complete a
      standardised written questionnaire. This was preceded by 30 in-depth interviews
      led with radio-oncological in-patients who currently received treatment. RESULTS:
      Radiotherapy patients reported a spectrum of major stresses, which showed a
      considerable individual variability. Many patients had experienced emotional
      crises during hospitalization for their radiation treatment. Most frequently the
      main social support was provided by relatives. Still, medical staff also played
      an important supportive role in alleviating emotional distress. Almost half of
      all patients appeared to have a generally positive attitude towards psychological
      counseling. CONCLUSION: This study is part of a psychosocial intervention project
      established in a radiotherapy department. Support is provided for patients
      directly, e.g. through crisis intervention, supportive therapy, creative therapy,
      etc. In addition, indirect intervention is aimed at enhancing psychosocial
      competences of the clinical staff, through lectures, case conferences and
      seminars.

PMID- 7631265
TI  - [Radical prostatectomy in localized prostatic carcinoma].

PMID- 7631264
TI  - Efficacy of prophylactic application of immunoglobulins in radiation induced
      mucositis.

PMID- 7631266
TI  - [Does the postoperative radiotherapy in node-negative breast cancer patients
      impair the survival?].

PMID- 7631267
TI  - [Radiotherapy and early orchiectomy in stage D1 prostatic carcinoma].

PMID- 7631268
TI  - [Leukemia in patients with breast carcinoma after adjuvant chemotherapy and/or
      postoperative radiotherapy].

PMID- 7631269
TI  - [Mammography screening of asymptomatic women: critical evaluation of published
      studies].

PMID- 7631270
TI  - On oral health in infants and toddlers.

PMID- 7631271
TI  - [Lost all sense of time. A talk with Dr. A.M. Debrunner. Interview by Klaus
      Reinhardt].

PMID- 7631272
TI  - [Orthopedics and time].
AB  - We can see into the future because we stand on the shoulders of giants. Descartes
      thought that the human body functioned like clock-work, but orthopaedic surgeons
      today know better. Man's life expectancy has increased, but has quality of life
      kept pace? The right moment is only a short instant. To await and then grasp it
      is part of the art of orthopaedics. But to reduce time to the present moment is
      to annihilate it. Time is the all-important fourth dimension which allows for
      change and thus for life.

PMID- 7631273
TI  - [Why long-term results?].
AB  - Lifelong histories are characteristic of orthopaedics. Long-term planning and
      guidance are essential features of orthopaedic thinking. The indications for
      operation are based on prognosis, which in turn we only know from long- term
      observations. Crucial to decision is the weighing of benefit against risk, with
      or without an operation. This mean: What are the dangers? What may be the
      benefit, not only for the moment, but in the long run? And what will happen, if
      we don't operate? Is there a chance of recovery or a risk of later deterioration?
      Thus, the study and a thorough knowledge of the natural course of a disorder and
      of the late results of operations are the basis of every orthopaedic treatment,
      particularly when operative. Further considerations include the ways and means of
      performing clinical research in orthopaedic surgery, its possibilities and
      obstacles, the necessity and value of retrospective studies, the issue of
      prophylactic operations and their inherent dangers, the political and social
      implications and, finally, the medical doctor's response to all this.

PMID- 7631274
TI  - [Long-term results in pediatric orthopedics].
AB  - Whether to treat deformities in childhood or even to operate on them is a
      difficult decision which may affect a patient's whole life. Most important is a
      sound knowledge of the natural course. Many 'deformities' are just normal
      variants, and others improve during the growth period, but some get worse and may
      cause damage in later life. However the outcome of operations is not always
      certain. Recurrence may occur as well as overcorrection; therefore, the long-term
      prognosis, with or without treatment, must be the guideline for indications. If
      an operation is considered, timing and extent of a correction are decisive. On
      the grounds of long-term outcome studies, guidelines can be established for the
      treatment of different diseases and deformities: upper extremities [dysmelia,
      elbow], spine [scoliosis, Scheuermann's disease, spondylolisthesis], hip
      (congenital dysplasia, Perthes' disease, slipped epiphysis), knee and feet
      (flatfoot, pes equinovarus).

PMID- 7631275
TI  - [The lax juvenile flexible flatfoot--disease or normal variant?].
AB  - The spectrum of normal variations of children's feet is extremely broad and often
      difficult to separate from pathological conditions. Especially the flexible
      flatfoot normally disappears during growth, and even if it persists up to adult
      life, it hardly has any pathological significance. The natural course taken even
      by severe flexible flatfoot in children leads to results that are as good, if not
      even better than when surgery had been performed; therefore, more reticence with
      surgical treatment in such cases is advocated.

PMID- 7631276
TI  - [Epiphysiolysis of the femoral head--can surgery prevent later arthritis?].
AB  - Slipped capital femoral epiphysis is one of the few orthopaedic emergencies. All
      orthopaedic surgeons agree that operation is the treatment of choice. In early
      stages, complete healing is possible. Fixation in situ is sufficient. If there is
      more severe dislocation of the head of the femur, the results become worse. More
      sophisticated and more difficult interventions aim at correction of the
      deformity, which may be a preliminary stage ['prearthrosis'] of osteoarthritis
      later in life. According to the extent of the slip, the surgeon may choose among
      different operations. The decision in a particular case is not easy.
      Complications are relatively frequent and sometimes severe. Long-term control
      show the late results and can thereby give guidelines for the surgeon's choice.
      Early diagnosis, however, is still decisive for a good prognosis in later life.
      As the disease is rather rare, the doctor who sees the patient first must be
      aware of it. Even at an early stage diagnosis can always be made on the basis of
      history, clinical findings and two X-rays.

PMID- 7631277
TI  - [The value of long-term results for quality control].
AB  - Quality control is as important today as always. In orthopaedic surgery this
      largely means follow-up of patients. Long-term thinking and planning need long
      term outcome studies, since orthopaedic therapy, especially an operation, has
      lifelong consequences. It is essential to know whether these are better or worse
      than the natural course of the disease. An operation is not always the best
      solution. Long-term and short-term continuous control are equally important; both
      have to be done despite of great practical difficulties. The assessment must
      become more patient-related than technique-related. Prospective studies cannot
      provide quick long-term answers; retrospective studies are needed, too. Political
      aspects complicate the issue. They are also addressed in this paper.

PMID- 7631278
TI  - [Multiple joint replacement in chronic rheumatoid arthritis: results,
      indications].
AB  - Rheumatoid arthritis, steadily progressive and affecting many joints, is a real
      challenge for the orthopaedic surgeon. Thorough assessment and long-term planning
      to maximize overall performance requires clear orthopaedic thinking based on wide
      experience. The final aim is to enable the patients to walk and be independent.
      Over the last 30 years, the surgery of the rheumatic diseases has become a well
      established specialty within orthopaedic surgery. Open synovectomy still has a
      place. In badly damaged joints, however, only prosthetic joint replacement has a
      fair chance. Total hip replacement is now a common procedure. Yet many problems
      regarding long-term performance remain unclear. This is even more pertinent for
      total knee replacement. Operations on the upper limbs must enable the patient to
      become less dependent of other people's help. Artificial shoulder joints have
      become more popular, and elbow joint replacement has been a particularly
      important field at the Wilhelm Schulthess Clinic. Multiple joint replacement is
      often necessary and can improve the quality of life for these badly stricken
      patients.

PMID- 7631279
TI  - [Total hip prosthesis with metal-on-metal slide matching--current developments
      based on long-term observations].
AB  - The first metal-on-metal artificial hip joints of the sixties (for example that
      of Mckee, Norwich) were soon replaced by models with polyethylene acetabular cups
      because of several shortcomings. 20 years later, however, a few patients were
      seen where such metal-to-metal joints still performed very well. Closer
      investigations revealed that with improved machining and a more perfect fit the
      failures of the first series could be eliminated and that these models were much
      less prone to wear than the ones using polyethylene. The author has developed and
      inserted such new prostheses, with good success so far.

PMID- 7631280
TI  - [Long-term results in hip endoprosthesis--problems, facts and outcome].
AB  - Analysis of long-term follow-up studies and of the pertinent literature leads to
      the conclusion, that the survival of artificial hip joints is still limited;
      therefore, the age of the patient is still a crucial element in the decision to
      operate. Also decisive for the indication are the patient's pain and suffering on
      the one hand and his expectations and needs on the other. A good indication can
      only be established by considering all these factors and weighing them against
      one another in a comprehensive, in-depth discussion between patient and surgeon.
      Other diseases are frequent in this age group and have also to be considered, as
      they might well affect the result. The diagnostics of implant loosening and the
      indications for revision are discussed.

PMID- 7631281
TI  - [Long-term results with women's feet].
AB  - When ladies complain of painful feet, they usually have hallux valgus. They can
      hardly accept that their ailment has something to do with too narrow shoes;
      therefore, it is not easy to explain to them, that usually the problem could be
      solved with comfortable large foot-wear and that an operation is not always
      necessary. On the other hand, operations for hallux valgus must not be labelled
      simply as a luxury procedure. Many patients can be relieved of pain and given the
      opportunity to wear acceptable fashionable shoes, provided that the appropriate
      method is chosen for each patient individually. This choice depends not only on
      the deformity of the foot, but to a high degree on age, profession and the
      situation of the patient, and what is most important, on her ideas and wishes.

PMID- 7631282
TI  - [Orthoses in patients with poliomyelitis].
AB  - Poliomyelitis, in spite of vaccination, is still a problem: in the third world as
      well as for the victims of the epidemics of the first half of this century, who
      now, becoming older, have growing difficulties to overcome their paralyses. They
      needed and still need orthoses for walking. How do they manage? And what can
      orthopedic technique offer them today?

PMID- 7631283
TI  - [Vascular effects of dihydropyridines].
AB  - Dihydropyridines are the most numerous available calcium antagonists. While
      belonging to the same group these drugs have physical, chemical, pharmacokinetic
      or pharmacodynamic properties which are sometimes specific and can explain
      differences in the targets and the vascular selectivity. These properties can be
      related to lipophilic or hydrophilic characteristics, existence or lack of 'use
      dependence', possible liaison to membrane phospholipids, and differences in
      elimination half lives. Selectivity of dihydropyridines also depends on the
      nature of the target structure (amount of intra-cellular calcium storage and
      mechanism of its release, electrophysiological properties of these cells) and of
      its pathological state (atherosclerosis and/or hypertension). Some of these
      properties could explain the anti-atherogenic effects, myocardial impact,
      cerebral and renal vascular flow and action in some pathological situations
      (Raynaud's syndrome, chronic arteriopathy, migraine...). A better knowledge of
      these different properties could lead to a more accurate choice of the drugs and
      to a decrease in the incidence of their side effects.

PMID- 7631284
TI  - [Which tests should be performed after phlebitis and/or pulmonary embolism?].
AB  - The lack of knowledge of the origin of venous thrombosis (VT) causes frustration
      and distress to the clinician. Some results published in the literature suggest a
      lot of potential aetiologies. Anyhow, we are far from getting a proof that a
      systematic and exhaustive search for a potential cause, for instance impairment
      of blood coagulation or infraclinical cancer, could be of benefit for the patient
      and could present a good cost/efficacy ratio. Consensus recommendations limit the
      extent of blood coagulation studies only to some precise clinical situations. New
      biological data evidencing a resistance to activated C protein in 20 to 50 per
      cent of VT cases, will likely bring new rules. As far as infraclinical cancers
      are concerned and whether their relationship to idiopathic VT is well
      established, it is still doubtful that such systematic heavy and expensive
      checking up could be of any benefit.

PMID- 7631285
TI  - [Thermal treatment in arterial diseases: an expensive placebo or an effective
      therapy?].
AB  - Each year, Royat (Auvergne) receives about 20,000 patients (80 per cent with
      intermittent claudication), treated by thermal gas (99.5 per cent of CO2). CO2
      therapy is dispensed with thermal water or with dry gas (general or local
      immersion and local subcutaneous injections of gas) during 3 weeks. Local
      vasodilator effects of CO2 have been demonstrated with several methods in Royat.
      Physiological and therapeutic effects of thermal CO2 therapy, also used in
      Germany and Central Europe, were precisely reported during the Consensus Congress
      of Fribourg in Brisgau (1989); more particularly, this treatment seems provide a
      reduced ability of haemoglobin to fix oxygen, and therefore a release of oxygen
      within the cells. Patients with peripheral arterial disease (stage 2) have a
      walking distance increased and post-exercise ankles' pressures improved after a
      thermal course of treatment in Royat, while a control group has no significant
      changes. The discussion will concern also the socio-economic aspects of thermal
      treatment of arterial diseases.

PMID- 7631286
TI  - [Myocardial ischemia detected by Holter monitoring: analysis of therapeutical
      trials realised in stable angina].
AB  - Silent myocardial ischaemia is the most frequent consequence of coronary artery
      disease and occurs in almost 70 per cent to 80 per cent of ischaemic episodes. In
      some studies, it has some predictive value of cardiovascular events either in
      stable or unstable angina or after myocardial infarction. In this last case, one
      year mortality is 30 per cent and 11 per cent respectively with and without
      silent ischaemia that has been recorded on the 8th day after myocardial
      infarction. This review has focused on controlled studies in patients with angina
      and Holter recorded ischaemia. Nitrates are very likely to be active substances
      on Holter recorded angina but no controlled studies have been performed to really
      demonstrate it. The efficacy of beta-blocking agents is well established with a
      60 per cent reduction in the number of ischaemic events and a 80 per cent
      reduction in total ischaemic duration. Nifedipine efficacy appears lower than
      that of beta-blockers with an evaluated mean reduction of 39 per cent for the
      number of events and of 43 per cent for duration of episodes. Diltiazem induces a
      48 per cent reduction of both ischaemic parameters. For drug associations,
      addition of a calcium antagonist to a beta-blocking agent provides only little
      benefit. The relationship between anti-ischaemic efficacy and long term
      prevention of cardiovascular events remains to be established for a given anti
      ischaemic therapy.

PMID- 7631287
TI  - [Comparative lipophilia of trandolapril and other converting enzyme inhibitors].
AB  - The lipophilicity of angiotensin converting enzyme inhibitors (ACE-I) available
      in France has been compared using two complementary methods. Studies have been
      performed both on active ACE-I and prodrugs. The first study used reverse phase
      high performance liquid chromatography (HPLC) in order to measure the n-octanol
      water partition coefficients. They were measured at 3 pH values (2.5, 4.7 and
      7.4). The second study was performed on the basis of computer drawn chemical
      formula. The lipophilic area to hydrophilic area ratio was calculated from the
      three dimensional structure of each ACE-I. A calculated n-octanol water partition
      coefficient was then determined. Whatever the method, a broad range of values was
      seen. The HPLC n-octanol water partition coefficient ranged from -1.86
      (captopril) to 1.02 (trandolaprilate). The lipophilic to hydrophilic ratio ranged
      from 1.33 (captopril) to 2.74 (trandolaprilate) and the computer determined n
      octanol water partition coefficient ranged from -0.36 (perindoprilate) to 0.69
      (quinaprilate). A strong correlation (r = 0.97 p = 0.0001) was found between the
      lipophilic/hydrophilic area ratio and the HPLC partition coefficient. The
      classification of the ACE-I was very close whatever the mode of determination.
      The less lipophilic ACE-I are lisinopril and captopril and the most lipophilic
      are quinalapril and trandolapril. Clinical consequences of such differences
      remain unknown.

PMID- 7631288
TI  - [Pharmacokinetic properties of Bilobalide and Ginkgolides A and B in healthy
      subjects after intravenous and oral administration of Ginkgo biloba extract (EGb
      761)].
AB  - The pharmacokinetics of Ginkgolide A, Ginkgolide B and Bilobalide, which are
      compounds extracted from the dried leaves of the Ginkgo biloba tree, were
      investigated in 12 young healthy volunteers (six men and six women; mean +/- SD
      age = 25 +/- 5 years) after single-dose administration of Ginkgo biloba extract.
      Subjects were given, on three occasions, Ginkgo biloba extract as a solution
      either orally (in fasting conditions and after a standard meal) or intravenously;
      corresponding to single doses of Ginkgolide A, Ginkgolide B and Bilobalide
      ranging from 0.90 mg to 3.36 mg. After each dosing, blood and urine samples were
      collected for up to 36 h and 48 h, for measurements of Ginkgolide A, Ginkgolide B
      and Bilobalide. Plasma and urine concentrations of these compounds were
      quantitatively measured by gas chromatography/mass spectrometry using negative
      chemical ionization, by applying a very sensitive method which allowed plasma
      concentrations as low as 0.2 ng/ml of each compound to be measured. When given
      orally, while fasting, the extents of bioavailability are high, as shown by
      bioavailability coefficients (FAUC) mean (+/- SD) values equal to 0.80 (+/-
      0.09), 0.88 (+/- 0.21) and 0.79 (+/- 0.30) for Ginkgolide A, Ginkgolide B and
      Bilobalide respectively. Food intake does not change AUC quantitatively but
      increases Tmax. For the three compounds of interest, after oral dosing while
      fasting, differences can be noted for the elimination half-lives (T1/2Z), which
      exhibit mean values equal to 4.50, 10.57 and 3.21 h, as well as mean residence
      times (MRT), equal to 5.86, 11.25 and 4.89 h, for Ginkgolide A, Ginkgolide B and
      Bilobalide respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7631289
TI  - [Drug-induced alopecia: review of the literature].
AB  - Drugs are capable of producing a wide spectrum of hair loss, ranging from barely
      detectable shedding to irreversible baldness. Drug-induced alopecia is usually
      described as a diffuse non-scarring alopecia which is reversible upon withdrawal
      of the drug. Only a few drugs (mainly antimitotic agents) routinely cause hair
      loss whereas many drugs may be the cause of isolated cases of alopecia. Some
      psychotropic drugs are likely to induce a drug-related alopecia. Case reports
      with tricyclic antidepressants rarely appear in the literature. It has been
      reported that 15 per cent of patients taking lithium developed hair thinning.
      Hair loss is reported secondary to some anticonvulsant agents mainly valproic
      acid. Among antihypertensive drugs, systemic or topic beta-adrenoceptor
      antagonists should be considered as possible  causes of hair loss. Hair loss from
      salicylates or nonsteroidal analgesics occurs in a very small percentage of
      patients. All anticoagulant and antithyroid drugs can produce hair loss. Diffuse
      hair loss can also be associated with the use of oral contraceptives, while
      receiving the pill and after stopping the drug. There is a long list of drugs
      that on occasion have been cited as causing hair loss: cimetidine, retinoids,
      amphetamines, bromocriptine and levodopa. A few isolated cases have been reported
      with some hypocholesterolaemic or anti-infectious agents. Diagnosis of drug
      induced alopecia remains difficult. The only way to confirm it is to see if an
      improvement occurs after cessation of the suspected drug. This side effect must
      be recognized because it may be a source of poor compliance in some patients.

PMID- 7631290
TI  - [Methodological analysis of phase IV clinical trials performed in hospital based
      on the Huriet Law ].
AB  - Since the implementation of the 'Huriet law', drugs in phase IV clinical trials
      are handled by the pharmaceutical Department of the 'Hopital Neuro-Cardiologique'
      (Lyon, France). The methodology of these trials is assessed by using a special
      assessment grid which enables a score for each protocol, with a maximal score of
      20 and a minimal one of minus 20. Although many limitations could be advanced,
      results of this study show that, among 39 assessed trials, 13 trials had weak
      methodology (score < or = 0), 16 are middle-quality trials (score between 0 and
      10) whereas 10 trials only can be considered as having a strong methodology
      (score > 10). So, a fairly large number of the organized phase IV trials have
      debatable quality. Moreover, their objective is questionable, that is essentially
      promotional, in spite of the 'Huriet law' and Persons Protection Committees.

PMID- 7631291
TI  - [Modification of the law of 20/12/88 on the protection of subjects participating
      in biomedical research].

PMID- 7631292
TI  - [Convulsive seizures in a patient treated with propafenone and ketoconazole].

PMID- 7631293
TI  - [Amineptin (Survector) abuse and pregnancy. Apropos of a case].

PMID- 7631294
TI  - [Acute pulmonary fibrosis in the course of treatment with fluorouracil and
      cisplatin].

PMID- 7631295
TI  - [Importance of dosage estimation in pharmacokinetic software USC PACK PC for
      digoxin toxicity: apropos of a case].

PMID- 7631296
TI  - [Opinion survey of European pharmacovigilance: opinion of French practitioners].

PMID- 7631297
TI  - [Peripheral vasodilators: from the hemodynamic effect to clinical benefit].
AB  - Patients with chronic occlusive arterial disease of lower limbs have an excess
      mortality due to associated cardiovascular diseases or cancer. They also have an
      important morbidity with a high prevalence of coronary artery diseases and
      strokes. In this context, the only benefit of peripheral vasodilators devoid of
      any effect on morbidity and mortality, could be only on quality of life.
      Haemodynamic effects of these drugs have been evaluated by several reproducible
      techniques in order to measure the peripheral blood flow (plethysmography, 133Xe
      clearance, transcutaneous oxygen-pressure, electromagnetic debimetry). An
      increase in blood flow has been demonstrated in patients receiving
      pentoxifylline, naftidrofuryl, or blufomedil in phase II clinical trials using
      these different methods. No general haemodynamic effect has been observed with
      these drugs which were better denominated vaso-active drugs. However the most
      relevant criteria remained to confirm a clinical benefit, particularly on
      intermittent claudication. Number of positive clinical trials in patients with
      intermittent claudication have been published, but from a methodological point of
      view few of them were suitable and demonstrated a statistically significant
      benefit. Criticisms were mainly related to the type of trial (cross-over is not
      recommended because of the drug-period effect), the lack of 'intention to treat'
      analysis, the inhomogeneity of the compared groups (for example different
      percentages of diabetics and excess of drop-outs). In spite of an established
      haemodynamic effect and of a demonstrated benefit in claudicants, peripheral
      vasodilators appear to have a slight interest in the global care of patients with
      occlusive arterial disease of lower limbs mainly on functional symptoms.

PMID- 7631298
TI  - [Drug evaluation methods in lower limb arteriopathy].
AB  - The prevalence and severity of chronic vascular leg disease explains the
      necessity to clarify methods for assessing it. Today the methods are both
      clinical and paraclinical. Clinically, they are based on the Fontaine and Leriche
      classification and appearance of ischaemic pain. Paraclinically, they are
      measuring distal blood pressure, artery output, micro-circulation, rheology, and
      tissular metabolism. But this approach must be also global, assessing coronary
      and carotid disease. Trials methodology includes a first step of explanatory
      studies by paraclinical ways and lastly pragmatic efficacy and tolerability
      studies. We recommend an accurate selection of patients and a stratification. The
      disease must be stable and the treatment and diet too. The trials should be
      randomised vs placebo. In conclusion we propose a multiparametric classification
      of the disease.

PMID- 7631299
TI  - Studies on phospholipid antibodies, APC-resistance and associated mutation in the
      coagulation factor V gene.
AB  - The influence of antibodies against phospholipids (PLa) on APC response was
      investigated in 155 women with a history of thromboembolism and/or repeated
      foetal losses. PLa were determined as antibodies against cardiolipin (CLa) and
      phosphatidyl serine (PSa) and as lupus anticoagulant (LA) tested by dilute
      Russell's Viper Venom time and by the Textarin/Ecarin ratio. APC-response was
      studied by a clotting (aPTT-based) and by an amidolytic (factor IXa-X-based)
      assay. A reduced response to APC (APC-resistance) was found in 49% of 65 PLa
      positive and in 13% of 90 PLa-negative samples (chi 2 = 23.9; p < 0.5 x 10(-4)).
      It was more common in the samples with LA, as compared to CLa+PSa positive (58%
      vs. 30%, not significant). The presence of the mutation causing Arg506-Gln
      substitution in coagulation factor V was investigated in 84 samples. The
      occurrence of the mutation in APC-resistant patients with CLa+PSa or with LA in
      one of the two assays was similar to those without PLa (84% and 100%,
      respectively). In the absence of APC resistance, the occurrence of the mutation
      was similar in the samples with and without PLa (14% vs. 11%). Samples with LA,
      determined by both tests used, comprised a special group where the frequency of
      the mutation in the APC resistant samples was significantly reduced (p < 0.01).
      In the latter samples, the pathogenic mechanism of APC resistance may be
      connected with the influence on phospholipid membranes.

PMID- 7631300
TI  - Anticoagulant and antithrombotic actions of a semisynthetic beta-1,3-glucan
      sulfate.
AB  - Sulfation of the natural polysaccharide curdlan results in anticoagulantly active
      beta-1,3-glucan sulfates whose activity depends on various structural parameters.
      In this study the anticoagulant and antithrombotic effects of one of these beta
      1,3-glucan sulfates (GS) were compared with those of a porcine mucosal heparin.
      GS produced a concentration dependent anticoagulant effect in all the global
      coagulation assays with the exception of the anti-Xa assay. The best activity was
      found in the APTT and the thrombin time assays indicating that protease
      generation and the direct inhibition of thrombin may be sites of actions of this
      agent. Whereas the anticoagulant activity of GS was approximately 5 fold lower
      compared to heparin, a 32 fold higher concentration (ED50 = 550 micrograms/kg)
      was needed for an antithrombotic effect similar to heparin (ED50 = 17.2
      micrograms/kg) in a rabbit model of stasis thrombosis. In contrast to this, when
      a rat model of clamping induced jugular vein occlusion was used to produce
      vascular obstruction, GS produced similar antithrombotic actions to heparin. At a
      250 micrograms/kg dosage, both agents doubled the number of clampings required
      for complete vascular obstruction. Since the mechanical injury to the blood
      vessel is the primary determinant of the thrombogenic response, GS may inhibit
      some of the pathophysiologic mechanisms responsible for the occlusion of the
      blood vessel. The current study also points to the fact that the global
      anticoagulant effects may not reflect the antithrombotic potential of newer
      sulfated carbohydrate derived drugs.

PMID- 7631301
TI  - On the action of a heparan-like glycosaminoglycan (Hemovasal) on the mechanism of
      haemostasis and fibrinolysis.
AB  - Hemovasal produced by Manetti-Roberts, Florence, Italy, is a glycosaminoglycan
      obtained from porcine intestinal mucosa which belongs to the family of heparan
      sulfates. The substance was examined On 36 male survivors of myocardial
      infarction with an interval of at least 6 months after the acute event. No
      anticoagulants were given and ASA was withdrawn at least 2 weeks before the
      trial. Hemovasal was administered in 3 different i.m. doses as single injections.
      A further group received a daily oral dose of 300 mg for one week. A comparable
      placebo group of patients as well as a group of healthy volunteers was run in
      parallel. The coagulation profile showed only a slight prolongation of the aPTT,
      a trace of diminution of Antithrombin III and no activation of Heparin cofactor
      II. The fibrinolytic system showed an enhancement of the diurnal increase of t-PA
      without an alteration of the total increase of this activity. There was a
      considerable and highly significant diminution of the PAI-1 activity. This was
      dose dependent and could be found after i.m. as well as after oral
      administration. It was assumed that the thrombolytic effect which was repeatedly
      described was a consequence of the diminution of PAI-1.

PMID- 7631302
TI  - A screening procedure to evaluate the anticoagulant activity and the kinetic
      behaviour of direct thrombin inhibitors.
AB  - The development of a fibrin clot microassay to define both the kinetic behaviour
      and the anticoagulant activity of direct thrombin inhibitors targeting various
      domains of thrombin (catalytic site, anion binding exosite or both) is described.
      Since classical kinetics studies are difficult to perform in a fibrin-clot assay,
      methodological conditions were selected in order to obtain a linear relationship
      between fibrin formation and the thrombin concentration i.e. 0.67 nM thrombin, 6
      microM fibrinogen, 5 minutes reaction. Under those conditions, the concentration
      of the complex thrombin-inhibitor can easily be calculated from a standard curve
      performed with increasing concentrations of thrombin and fitted versus the total
      inhibitor concentration using adapted equations. To detect the slow establishment
      of the thrombin inhibition, results obtained with a protocol in which the
      inhibitor is pre-incubated with thrombin before the addition of fibrinogen is
      compared to a protocol in which the inhibitor is pre-incubated with fibrinogen
      before thrombin is added. Our assay which is validated using different types of
      thrombin inhibitors (classical competitive: NAPAP and hirudin 55-65; tight
      binding: r-hirudin; slow tight binding: DUP-714), provides a rapid screening
      protocol allowing to evaluate the biochemical and anticoagulant properties of any
      direct thrombin inhibitor.

PMID- 7631303
TI  - Association of lipoprotein(a) with atherothrombotic events and fibrinolytic
      variables. A case-control study.
AB  - Elevated plasma levels of lipoprotein(a) [Lp(a)] have been associated with an
      increased risk of cardiovascular disease. The aim of the present study was to
      investigate whether Lp(a) plasma levels were associated with subsequent ischemic
      events and with fibrinolytic variables in patients with established
      atherosclerotic disease enrolled in the prospective PLAT study. Lp(a) levels and
      fibrinolytic variables in 37 atherosclerotic patients who subsequently developed
      an atherothrombotic event during the first year of follow-up (cases) were
      compared with those in paired controls, matched for age, sex, diagnosis at
      enrollment and lipid pattern, who remained free from vascular events during the
      same time frame. Median and mean Lp(a) levels were similar in cases (6.05 mg/dl;
      13.8 +/- 19.4 mg/dl) and controls (6.05 mg/dl; 17.1 +/- 21.6 mg/dl). In the whole
      group plasma Lp(a) levels correlated significantly with the increase of t-PA
      antigen (r = 0.368; p = 0.002) and fibrinolytic activity (r = 0.410; p = 0.001)
      induced by venous stasis but not with baseline fibrinolytic variables. These
      findings indicate that in patients with established atherosclerotic disease Lp(a)
      may interfere in vivo with the fibrinolytic process but is not predictive of
      subsequent ischemic events.

PMID- 7631304
TI  - Amidolytic assay of factor XI in human plasma--significance of kallikrein for the
      activity measured.
AB  - Factor XI (FXI) deficiency is associated with an abnormal bleeding state. The
      extent of bleeding does not correlate well with the plasma concentration of FXI,
      and it has been suggested that also unknown factors interfere with the bleeding
      tendency. In a recent paper (Thromb. Res. 74, 477-485, 1994) we found that FXIa
      activated in human plasma was present in association with part of factor XIIa
      (FXIIa) and part of kallikrein, influencing their functional activities. Should
      the activity level of FXIa also be altered by the other contact factors this
      might provide one approach to the problem of the failure of assays of FXIa to
      correlate with bleeding tendency. In the present study we have developed an assay
      procedure for FXIa based on its amidolytic (S-2366) activity, and allowing at the
      same time a quantification of the amount of FXIa associated to kallikrein. The
      total amidase activity obtained was separated into two main fractions by use of
      soybean trypsin inhibitor (STI), corn inhibitor (CI) and lima bean trypsin
      inhibitor (LTI). One fraction contained free FXIa which could be specifically
      blocked by LTI. An inhibitor resistant fraction was found to contain FXIa
      inactive in association with kallikrein. The content of FXIa could be assessed in
      experiments with mixtures of normal plasma and plasma deficient in prekallikrein,
      and was taken into account in the calculations. This fraction increased during
      storage of plasma at -70 degrees C. To obtain stable and comparable assay
      conditions the method was based on plasma stored for at least four weeks. The
      specificity of the method was verified by parallel radial immunodiffusion tests.
      The results imply that the activity level of FXIa is dependent on kallikrein
      present. If the experimental results has relevance to the situation under
      physiological conditions, they indicate one possible cause of the failure of
      assays of FXI to correlate with bleeding tendency.

PMID- 7631306
TI  - Inhibition of fibrinolytic activity by hyaluronan and its alcohol ester
      derivatives.

PMID- 7631307
TI  - Determination of specific activity of recombinant hirudin using a thrombin
      titration method.

PMID- 7631305
TI  - Nonsense mutation Arg197stop in a Dutch family with type 1 hereditary
      antithrombin (AT) deficiency causing thrombophilia.

PMID- 7631308
TI  - Cleavage of high molecular weight kininogen in ascites and plasma of patients
      with cirrhosis.
AB  - The vasoactive peptide bradykinin may be involved in the pathogenesis of
      vasodilation, which has been considered the initiating event of ascites formation
      in cirrhotic patents. Since bradykinin is generated through the cleavage of high
      molecular weight kininogen (HK) by kallikrein, we looked for the cleavage of HK
      by an immunoblotting technique in plasma and ascitic fluid of 28 patients with
      cirrhosis of different etiology. The majority of patients showed massive cleavage
      of HK in ascitic fluid (median 50% of total HK; range 23-100%). Patients with
      severe ascites had more cleaved HK in plasma (29%; range 8-38%) than normal
      subjects (22%; range 11-32) (P = 0.02). Patients with high levels of plasma renin
      activity (5-60 ng/ml/hour), which is considered a consequence of peripheral
      vasodilation, had more plasma cleaved HK (31%; range 18-38)(p = 0.0097) than
      normals. Thus, our data support the view that cleavage of HK could play a role in
      the pathogenesis of vasodilation and ascites formation in patients with
      decompensated cirrhosis.

PMID- 7631309
TI  - A partial factor V deficiency in anticoagulated lyophilized plasmas has been
      identified as a cause of the international normalized ratio discrepancy in the
      external quality assessment scheme.
AB  - Lyophilized normal and anticoagulated plasmas are increasingly used in External
      Quality Assessment schemes (EQAS) to assess the quality of performance of
      laboratories engaged in the control of oral anticoagulant therapy by means of the
      International Normalized Ratio (INR) system and for the standardization of the
      prothrombin time (PT). The main feature of the INR system is that the value
      measured for an individual plasma should be independent of the reagent used. This
      holds true only if the variable factors influencing the responsiveness of the
      reagents are the vitamin K-dependent clotting factors, the other factors being
      constant and within normal limits. We provide evidence that even a partial factor
      V (FV) deficiency (FV activity < 60 U/dl) in anticoagulated plasmas can be
      responsible for discrepancies between INR values as measured for a single
      lyophilized or fresh plasma by different reagents and that the discrepancy is
      proportional to and magnified by the International Sensitivity Index (ISI) of the
      reagent used. The greater the difference between ISI values, the wider the gap
      between INR values. Since FV is one of the most labile plasma clotting factors,
      its activity is likely to be lost during freeze-drying. Hence, we recommend a
      thorough control of the FV activity in commercial and home-made lyophilized
      plasmas before their use in EQAS and in the standardization of the PT.

PMID- 7631310
TI  - Peripheral benzodiazepine ligands inhibit aggregation and thromboxane synthesis
      induced by arachidonic acid in rabbit platelets in vitro.
AB  - Seven compounds having varying affinities for peripheral benzodiazepine (p sites)
      were evaluated in vitro as inhibitors of arachidonic acid-induced rabbit platelet
      aggregation and thromboxane B2 (TXB2) synthesis. With the exception of
      flumazenil, all compounds inhibited both parameters with IC50 values ranging from
      0.19 to 3.5 microM, with a significant correlation between the inhibition of
      aggregation and the synthesis of thromboxane B2. The antiaggregatory effect was
      stereoselective, and inhibition was increased when cellular penetration was
      favoured by increasing the volume of the organic solvent. The order of potency
      these compounds is consistent with an effect at intracellular p sites (Ro5-4864 >
      PK14067 > PK 11195 >> PK 14068 > or = clonazepam > or = diazepam >>> flumazenil).
      However, the correlation between the aggregation inhibition and the synthesis of
      TXB2 suggests that microsomal cyclooxygenase may be the intracellular target of
      these ligands. We therefore propose that this enzyme possesses a site for
      benzodiazepine ligands which may share certain characteristics with the
      peripheral benzodiazepine receptor.

PMID- 7631311
TI  - Plasma cryoprecipitation studies: major increase in fibrinogen yield by albumin
      enrichment of plasma.
AB  - The present studies compared fibrinogen yields of cryoprecipitate (Cr) obtained
      under differing conditions, and focused on yields from albumin enriched plasma.
      Addition of human albumin to fresh plasma collected into CPDA-1, citrate, or
      heparin (4 U/ml) resulted in an average of 2.8 fold (+/- 0.34 SD, n = 17)
      increase in yields of Cr fibrinogen. This albumin effect was shown with
      undefatted and defatted albumin, fibrinogen yields increasing in the range of 2-6
      g of albumin added/dl of plasma and plateauing thereafter. Similarly increased
      were yields of fibronectin, plasminogen and factor XIII, but not of factor VIII
      or of von Willebrand factor. By electrophoretic analyses, Cr fibrinogen from
      albumin enriched and that from untreated plasma did not differ. Fibrin related
      measurements disclosed that the albumin enhancement of fibrinogen yield did not
      result form increased fibrin formation in Cr. This enhancement was shown in
      plasma that had been enriched with soluble fibrin to increase its yield and in
      that which had been subjected to hirudin, to high ionic strength, or to dilution
      to decrease its Cr fibrinogen yield. The results suggest a water exclusion
      effect, inducing cryoprecipitation of otherwise soluble fibrin/fibrinogen
      complexes.

PMID- 7631312
TI  - Arachidonic acid metabolism in platelets of patients with essential
      thrombocythaemia.
AB  - Platelet aggregation tests and studies comprising [14C] arachidonic acid [14C]AA
      incorporation, release and metabolism were performed in resting and
      thrombinstimulated platelets of 11 patients with essential thrombocythaemia (ET)
      and 11 normal subjects. Nine patients had abnormal aggregation tests.
      Incorporation and distribution of [14C]AA in main platelet phospholipids (PLs)
      was similar in both groups. Activated platelets of patients with ET released more
      radioactivity from PLs that controls (13.7 +/- 5.4% versus 8.2 +/- 1.9%, p <
      0.01). The formation of 12-L-hydroxy-5,8,10-heptadecatrienoic acid (HHT) was also
      increased (3.3 +/- 1.4% of total radioactivity versus 1.6 +/- 0.4% in controls (p
      < 0.0001). The same results were obtained for the generation of thromboxane B2 (p
      < 0.01). We did not detect differences in the formation of 12-L-hydroxy-
      5,8,10,14-eicosatetraenoic acid (3.3 +/- 1.7% in patents versus 2.0 +/- 0.5% in
      controls). These results indicate that platelets of patients with ET have an
      increased activity of phospholipases and suggest a facilitated metabolism of
      arachidonate by the prostaglandinsynthetase pathway. Our results also demonstrate
      that impairment of aggregation tests in these patients was not due to a defective
      activity of the enzymes involved in the release and metabolism of AA by
      platelets.

PMID- 7631313
TI  - Fibrinogenemia Tampere--a dysfibrinogenemia with defective gelation and
      thromboembolic disease.
AB  - Fibrinogen Tampere was found in a woman with severe thromboembolic disease. The
      thrombin induced clotting time of her plasma and purified fibrinogen was slightly
      prolonged. The activation of fibrinogen Tampere appeared to be normal but
      subsequent gelation was defective. We studied fibrin gels formed at different
      ionic strengths and at different fibrinogen and calcium concentrations by liquid
      permeation, turbidity, and 3D laser microscopy. Crosslinking was studied by SDS
      gel electrophoresis. The gels formed from fibrinogen Tampere were at ionic
      strength above 0.2 much tighter and had lower fiber mass-length ratios than
      normal gels as judged by permeability and turbidity data. At ionic strength 0.15
      and at different calcium concentrations analysis by permeability showed the same
      results for fibrinogen Tampere as for normal gels. Analysis by turbidity at ionic
      strength 0.15 suggested swelling of the fibers at low calcium concentrations. 3D
      microscopy revealed perturbed clot architecture under all conditions. In fibrin
      gels from fibrinogen Tampere, the gamma-chain crosslinking was normal but the
      crosslinking of alpha-chains was delayed at ionic strength 0.2 and also at lower
      ionic strengths on lowering the calcium concentration. The abnormal gelation may
      be due to a mutation in the fibrinogen molecule. Tendency to form tight fibrin
      gels and/or insufficient crosslinked fibrin matrix may be pathogenetic in this
      thrombotic disease.

PMID- 7631314
TI  - A new sensitive membrane based ELISA technique for instantaneous D.Dimer
      evaluation in emergency.
AB  - D.Dimer is currently used as a diagnotic help in thromboembolic events. The first
      application widely validated concerns the exclusion diagnosis of deep vein
      thrombosis and pulmonary embolism. In this context D.Dimer measurements must be
      performed individually and they must offer a good accuracy in evaluating the
      clinical decision threshold which is of 0.5 micrograms/ml when D.Dimer is
      expressed as initial fibrinogen equivalent. For this objective we report a new
      membrane based ELISA technique, which uses an immunofiltration device and two
      complementary monoclonal antibodies. The first one is coated onto the membrane
      and is used for the D.Dimer capture. The bound analyte is then revealed later
      using the second monoclonal antibody coupled to alkaline phosphatase. The assay
      is performed in less than 10 minutes and it can be used instantaneously by the
      clinical laboratories in emergency situations. Only 200 microliters of a standard
      citrated plasma are required. All samples containing more than 0.5 micrograms/ml
      D.Dimer produce a color development which intensity is a relation of the D.Dimer
      concentration. All specimen with levels below 0.3 micrograms/ml give negative
      tests, whereas a grey zone is present between 0.3 and 0.5 micrograms/ml. This
      assay offers all the specifications required by its applications to the exclusion
      diagnosis of deep vein thrombosis and pulmonary embolism.

PMID- 7631315
TI  - Measuring plasma fibrinogen levels in patients with liver cirrhosis. The
      occurrence of proteolytic fibrin(ogen) degradation products and their influence
      on several fibrinogen assays.
AB  - In patients with liver cirrhosis the fibrinogen molecule is under constant attack
      of various proteolytic enzymes, which might affect results of the different assay
      systems for fibrinogen. We therefore studied the measurement of fibrinogen in the
      plasma of patients with mild, moderate and severe cirrhosis of the liver.
      Fibrinogen levels were measured with the Clauss method (functional fibrinogen);
      an enzyme immuno assay (EIA) for HMW + L MW fibrinogen; and an assay that
      measures the total clottable fibrinogen. With all three methods we found normal
      or slightly increased fibrinogen levels in patients with mild or moderate
      cirrhosis, whereas patients with severe cirrhosis had decreased levels. No
      evidence was found for increased partial fibrinogen proteolysis, resulting in
      increases of LMW'-fibrinogen in cirrhotic patients. We further observed that
      fibrinogen degradation products levels increased slightly with the severity of
      the disease, but were still in the normal range in patients with severe
      cirrhosis. This indicates a very low level of primary fibrinolysis. Fibrin
      degradation products levels increased much stronger, which points to
      intravascular coagulation. The levels of the fibrin degradation products remained
      below the level where they are expected to influence the Clauss assay. In
      patients with liver cirrhosis the measurement of plasma fibrinogen levels with
      the three studied methods give comparable results. We suggest to apply the Clauss
      assay in cirrhotic patients because of this and because it has good
      reproducibility and because the test is cheap, quick and easy to perform.

PMID- 7631317
TI  - Guiding principles for the use of biological markers in the assessment of human
      exposure to environmental factors: an integrative approach of epidemiology and
      toxicology. Report on a WHO consultation. WHO Regional Office for Europe.
AB  - Using biological markers can potentially improve the way in which exposure to
      environmental factors is assessed. At present, however, only a few valid
      biological markers are available that can be effectively used in epidemiological
      studies and the assessment of risk. Future application of biological markers
      requires collaboration between toxicologists and epidemiologists. To establish
      guiding principles in this field, the Bilthoven Division of the WHO European
      Centre for Environment and Health organized a consultation. The participants
      critically reviewed existing methods for the use of biological markers in
      assessing exposure, and discussed the justification and criteria for biomarker
      use, the limitations of biomarker-related assessments, confounder problems,
      aspects of study design, validation needs and ethical issues. Recommendations
      were made covering each of the topics discussed, and it is hoped that they will
      serve as guiding principles.

PMID- 7631316
TI  - Hormonal contraception and platelet function.

PMID- 7631318
TI  - Guiding Principles for the Use of Biological Markers in the Assessment of Human
      Exposure to Environmental Factors--an Integrative Approach of Epidemiology and
      Toxicology. Papers presented at a WHO workshop. Cracow, Poland, 13-14 September
      1993.

PMID- 7631319
TI  - Biomarkers of exposure versus parameters of external exposure; practical
      applications in estimating health risks.
AB  - To estimate the health risk of a specific part of the population due to an
      environmental factor, the exposure can be measured and consecutively evaluated by
      means of toxicity data from the literature. To facilitate the choice between
      parameters of external exposure (ExEx) versus biomarkers of exposure (BmEx), a
      guideline is proposed, which consists of eleven considerations. (1) Local effects
      (directly on airways, eyes or skin) usually require ExEx, whereas systemic
      effects call for BmEx. (2) Determination of the contribution of a specific,
      environmental source among multiple, e.g., non-environmental sources of a
      substance calls for ExEx. (3) The availability of a reliable exposure-response
      relationship for the effect considered and of a health-based limit value;
      theoretically a relationship based on BmEx can be more reliable. (4) The
      possibility to determine reliably the exposure data that are needed, depending on
      the time and duration of the sampling with respect to the pattern of the external
      exposure, on the number of samples, and the toxicokinetic properties. (5)
      Inconvenient route of entry points to BmEx. (6) The presence of a group at risk
      due to intake-related behaviour or toxicokinetics calls for BmEx. (7) In the case
      of non-specificity of BmEx due to other substances the increase or decrease of
      the effect predicting value should be evaluated. (8) Substantial probability of
      effects calls for BmEx. (9) Feasibility of sampling technique and reliability of
      the analysis. (10) Acceptance by the public points to BmEx. (11) Cost
      effectiveness. Several examples illustrate this guideline.

PMID- 7631320
TI  - Levels of pollutants and their metabolites: exposures to organic substances.
AB  - The measurement of levels of organic pollutants and/or their metabolites in body
      tissues or fluids are specific markers of internal dose and, provided that the
      pharmacokinetic properties of the compounds in question are known, these levels
      may also be used as predictors of effects. Although historical data still remain
      to be very useful in environmental studies, more reliable exposure measures than
      combination of environmental levels and such estimators as residential history,
      job titles, life-style habits, individual perceptions, etc., are highly
      desirable. This has been clearly demonstrated in studies with 2,3,7,8
      tetrachlorndibenzo-p-dioxin (TCDD), where more recent measurements of serum
      concentrations in persons earlier classified as belonging to exposed groups have
      indicated that severe misclassifications may have occurred in previously
      epidemiological studies. This also demonstrates that, in retrospective studies,
      levels of persistent organic compounds are useful as markers of exposure, as
      their tissue levels mainly reflect previous exposures. However, most organic
      compounds are readily metabolized and excreted from the human body, and in many
      instances it will not be possible with current methodology and instrumentation to
      detect transient organic pollutants at low levels in the blood. In most cases,
      the use of urine samples offers a better opportunity to provide samples
      containing detectable levels. Therefore, the measurement of non-persistent
      organic substances and/or their metabolites may find potential use in prospective
      environmental health studies, but the predictive value highly depends on proper
      timing and frequency of sampling according to their toxicokinetic behaviour. A
      few examples on the use of organic compounds and/or metabolites as biomarkers are
      given, e.g., polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs),
      polychlorinated biphenyls (PCBs), polybrominated biphenyls (PBBs), ochratoxin A,
      polycyclic aromatic hydrocarbons (PAHs) and cooked food mutagens.

PMID- 7631321
TI  - Application of biomarkers in heavily polluted industrialized areas of countries
      of central and Eastern Europe.

PMID- 7631322
TI  - Use of human hair as a biomarker in the assessment of exposure to pollutants in
      occupational and environmental settings.
AB  - The use of human hair analysis technique is far from being the universal tool for
      monitoring exposures to environmental pollutants and considering the broad
      spectrum of pollutants encountered in the general environment one can hardly
      expect that such a screening tool would ever exist. However, for a majority of
      toxic trace metals this technique has proved to be a well-suited biological
      marker of occupational and environmental exposure of man. One of the essential
      conditions for ensuring the realistic evaluation of excessive population exposure
      is the examination of sufficiently large population groups and the use of group
      diagnostics methodology in environmental epidemiology studies. The method of hair
      analysis appears to be ideally suited for use in pilot prospective studies. If an
      excessive exposure is detected it is recommendable that the epidemiological
      examination be completed by analyses of other biological materials, most often
      blood and urine, in order to obtain a closer specification of the degree of
      exposure in the respective population.

PMID- 7631323
TI  - Early biochemical markers of effects: enzyme induction, oncogene activation and
      markers of oxidative damage.
AB  - Experimental carcinogenicity studies focus on identification of single
      carcinogens. Humans, however, appear exposed to a variety of low doses of
      carcinogens. Furthermore, few chemical entities are carcinogenic or toxic per se,
      but require metabolic activation to form ultimate carcinogens or toxins. In
      contrast to experimental animals, humans show considerable difference in genetic
      properties. In that situation it is particularly important to estimate individual
      capability for metabolic activation. To an increasing extent, activation includes
      formation of toxic oxygen metabolites. Particular targets for activated species
      are DNA and lipids; in particular low-density lipoproteins (LDL). Modifications
      of DNA are important for initiating the multistep process of carcinogenesis, in
      particular if oncogenes are activated or if tumor supressor genes are
      inactivated. Such DNA modification can be identical regardless of the reactive
      specimens being a xenobiotic or an oxygen species. Modification of LDL can start
      the process of atherosclerosis by transforming macrophages into foam cells,
      deposited as fatty streaks in the arterial wall. Biomarkers for activation
      capacity of xenobiotics include the use of prototype substrates and molecular
      techniques to determine genetic polymorphisms. Oxidative DNA modification can be
      measured from urinary excretion of oxidatively modified deoxynucleosides,
      particularly guanosine. Future efforts have to include individual measurements in
      order to improve the 'resolution' of molecular epidemiological approaches.

PMID- 7631324
TI  - Biokinetics and stability aspects of biomarkers: recommendations for application
      in population studies.
AB  - The knowledge of the toxicokinetics of chemicals is an important prerequisite of
      biological monitoring of exposure. Kinetic data allow to determine whether the
      test is likely to reflect the recent exposure or to integrate the exposure over a
      certain period of time. They are necessary to select the appropriate parameter,
      biological specimen and sampling time by taking into account the type of exposure
      and the sensitivity of the analytical method. Various mathematical models have
      been developed to provide a global and quantitative description of the behavior
      of the chemical in the organism. In practice, however, the parameter to which one
      usually refers is the elimination half-life of the biomarker which reflects both
      the affinity of the chemical for the biological matrix and the efficiency of
      excretory or metabolic processes. Since chemically-induced diseases usually
      develop following repeated exposures over many years, markers which are the most
      useful for population studies are those integrating the dose received by the
      organism or by the target organ(s) over a toxicologically relevant period of time
      exposure. For a reliable application of biological monitoring in population
      studies, information must be collected on the stability of the biomarker and the
      precautions to be taken during transportation and storage of samples. The factors
      most likely to affect the stability of the parameter are evaporation, chemical
      deterioration, precipitation, adsorption on vessel surfaces and contamination.
      This paper formulates a series of practical recommendations to prevent or
      minimize variations in the pre-analytical phase which might be caused by these
      factors.

PMID- 7631325
TI  - Validity criteria for the use of biological markers of exposure to chemical
      agents in environmental epidemiology.
AB  - Biomarkers may prove very useful in increasing the precision of exposure
      estimates during field epidemiological studies of environmental and occupational
      exposures. However, the determination of validity of exposure biomarkers is a
      laborious process. It is also a process that needs collaboration between
      laboratory and field scientists if biological markers of exposure are to be
      useful tools in environmental epidemiology.

PMID- 7631326
TI  - Design of studies for validation of biomarkers of exposure and their effective
      use in environmental epidemiology.
AB  - Studies in environmental epidemiology suffer from the problem that precise
      assessment of relevant exposures is difficult to undertake, in particular on an
      individual level. There is much hope that biomarkers may help to move to much
      more specific studies. However, a variety of issues on the role of biomarkers and
      their validity need to be clarified beforehand. This paper summarizes issues of
      the design of studies for validation of biomarkers. Emphasis must be on
      collecting concurrent information on external dose and related biomarker status
      (internal dose) for individual subjects.

PMID- 7631327
TI  - Application of biological markers in cancer environmental epidemiology.

PMID- 7631328
TI  - Application of biomarkers in population studies for respiratory non-malignant
      diseases.
AB  - Though the use of biomarkers has been mainly suggested for cancer studies, the
      possibility of its use in non malignant disease is considered. Markers of
      internal dose, markers of biologically effective dose and markers of early
      biologically effect have been typically used in basic research and, more
      recently, in epidemiology to characterize genotoxic carcinogenic agents. These
      markers (e.g. adducts to DNA or proteins) may be used mainly in the presence of
      chronic exposure to toxic agents (e.g. benzene or benzopyrene), additional
      markers such as carboxyhemoglobin, expired air to measure various VOC and heavy
      metals in biological fluids are also considered in the paper. Since airway
      obstructive disease (asthma, chronic bronchitis, emphysema) are the main
      disorders influenced by environmental factors (including air pollution), markers
      of individual susceptibility, such as atopy increased responsiveness of airways,
      initial level of lung function, must be considered for a more precise evaluation
      of the relationship between environmental exposure and health effects. Currently,
      the application of the determination of markers of exposure in non malignant
      disorders is very limited. In fact, the relationships between acute adverse
      respiratory effects and the exposure to air pollutants appears difficult since
      markers for common air pollutants are not available, and their detection appears
      difficult in acute conditions. Characterization of long term exposure may be
      performed in organ fluids (blood, urine, saliva) however it is important to
      recognize that concentration at that level may not reflect that observed in the
      target organ (e.g. lung).

PMID- 7631329
TI  - Morbidity, mortality, and antihypertensive treatment effects by extent of
      atherosclerosis in older adults with isolated systolic hypertension.
AB  - BACKGROUND AND PURPOSE: The Systolic Hypertension in the Elderly Program (SHEP)
      demonstrated a significant reduction in stroke and coronary event rates among
      participants randomly assigned to active blood pressure treatment. Selected
      participants were evaluated for peripheral atherosclerosis and followed up for
      cardiovascular events beyond the end of the SHEP trial. Antihypertensive
      treatment effects were evaluated based on the presence or absence of clinical or
      subclinical atherosclerosis. METHODS: As an ancillary study to SHEP, 190
      participants at the Pittsburgh center were evaluated for peripheral
      atherosclerosis, defined as either an internal carotid stenosis (by duplex scan)
      or lower extremity arterial disease (identified by ankle blood pressure).
      Participants were subsequently followed up for cardiovascular events. RESULTS:
      Estimates of 4-year mortality rates were 4.8% for participants with no
      atherosclerosis, 16.7% for those with subclinical atherosclerosis, and 23% among
      those with clinical evidence of atherosclerosis (P < .001). Fatal plus nonfatal
      cardiovascular event rates were 10.9%, 29.8%, and 58.3% for the three groups,
      respectively (P < .001). Differences remained significant after adjustment for
      age, sex, treatment assignment, smoking, and high-density lipoprotein
      cholesterol. Individuals assigned to placebo at the beginning of SHEP had higher
      cardiovascular event rates than individuals assigned to active treatment (P =
      .011), with the most striking difference 3 or more years after the end of the
      SHEP trial. When this analysis was stratified by the presence or absence of
      detectable atherosclerosis, the absolute treatment effect was largest among those
      with evidence of disease. CONCLUSIONS: Individuals with systolic hypertension and
      evidence of peripheral atherosclerosis are at high risk for cardiovascular
      events. Targeting this group for antihypertensive therapy would result in the
      prevention of a large number of cardiovascular events.

PMID- 7631330
TI  - Detection of carotid stenosis. From NASCET results to clinical practice.
AB  - BACKGROUND AND PURPOSE: Results from large multicenter studies have shown that
      carotid endarterectomy, performed with low perioperative morbidity and mortality,
      is beneficial for patients with symptomatic carotid stenosis > or = 70% as
      calculated according to strict angiographic criteria. To apply these results in
      clinical practice, individual institutions should determine whether locally
      implemented duplex ultrasonography adequately identifies patients with > or = 70%
      stenosis and whether the degree of stenosis reported by local angiographers
      correlates with strict angiographic measurements. METHODS: We compared estimates
      of carotid stenosis obtained by duplex ultrasonography and the radiologists'
      reports from conventional cerebral angiography with each other and with results
      obtained using North American Symptomatic Carotid Endarterectomy Trial (NASCET)
      criteria. RESULTS: One hundred seventy-one vessels were available for review. In
      155 (91%) of the cases, the reports from the ultrasound and angiogram were in
      agreement with regard to whether the stenosis was > or = 70% or < 70%. In 11 of
      the 16 cases where there was a disparity between the studies, the ultrasound was
      in closer agreement with measurements obtained using NASCET criteria. Nine of the
      angiography reports overestimated the degree of stenosis compared with NASCET
      measurements; twice angiography underestimated the stenosis. Twice the ultrasound
      underestimated the stenosis, and three times it overestimated the stenosis.
      CONCLUSIONS: Duplex ultrasonography was highly sensitive for detecting
      significant carotid stenosis at our institution; however, angiography reports
      often graded the degree of stenosis to be more severe than measurements obtained
      using NASCET criteria. Institutions that evaluate patients for carotid
      endarterectomy should investigate the correlation between their ultrasound and
      angiographic studies so that the results of carotid endarterectomy trials can be
      accurately applied.

PMID- 7631331
TI  - Angiotensin-converting enzyme gene deletion polymorphism. A new risk factor for
      lacunar stroke but not carotid atheroma.
AB  - BACKGROUND AND PURPOSE: A deletion (D)/insertion (I) polymorphism in the
      angiotensin-converting enzyme gene has been associated with myocardial
      infarction. Its relations to both stroke and atheroma remain uncertain. We
      examined its role as a risk factor in patients with cerebrovascular disease and
      its relation to carotid atheroma. METHODS: One hundred one patients with
      symptomatic carotid artery territory cerebral ischemia were compared with 137 age
      matched control subjects. In the patient group, carotid atheroma was assessed by
      measurement of degree of carotid stenosis and intima-media thickness with high
      resolution duplex ultrasound. The D/I polymorphism was examined using the
      polymerase chain reaction. RESULTS: D:I allele frequency was 0.59:0.41 in case
      subjects and 0.48:0.52 in control subjects (P = .01). The DD genotype was more
      common in patients with cerebrovascular disease compared with control subjects
      (36/101 versus 30/137, P = .02). The DD genotype conferred a relative risk of any
      type of cerebrovascular disease of 1.98 (95% confidence interval [CI], 1.11 to
      3.51; P = .02). However, this was largely due to a strong association in the 18
      patients with lacunar stroke, in whom the D:I ratio was 0.75:0.25 (P = .0097
      versus control subjects). The odds ratio for lacunar stroke associated with the
      DD genotype was 5.6 (95% CI, 2.0 to 15.7) and was still significant at 4.40 (95%
      CI, 1.45 to 12.6; P < .009) after controlling for other risk factors. There was
      no significant association between angiotensin-converting enzyme genotype and
      cerebrovascular disease due to large-vessel stenosis. There was no association
      between genotype and age, sex, smoking history, diabetes, or cholesterol level.
      CONCLUSIONS: The deletion polymorphism in the angiotensin-converting enzyme gene
      is a new independent risk factor for lacunar stroke but is not a risk factor for
      stroke associated with carotid stenosis.

PMID- 7631332
TI  - Validation of a population screening questionnaire to assess prevalence of
      stroke.
AB  - BACKGROUND AND PURPOSE: A cross-sectional survey is the best method for
      determining the prevalence of a chronic condition such as stroke. Before
      embarking on a large population study, a valid screening instrument is necessary.
      This study aimed to validate a self-completion postal screening questionnaire for
      assessing lifetime history of stroke. METHODS: A random sample of 2000 people
      aged 45 years and over was selected from the Family Health Services Authority
      register. A brief self-completion questionnaire requesting self-reported history
      of stroke was mailed to each individual. Responders reporting a history of stroke
      received a request for a standardized home assessment visit. Confirmation of the
      diagnosis of stroke was made based on information from the home visit together
      with multiple sources of case ascertainment. False-negative responses and
      assessment of nonresponse bias were documented. RESULTS: The response rate for
      the questionnaire was 88%. Of the sample, 120 (6%) who were wrongly registered
      were excluded; 173 (10%) of the 1663 responders reported a history of stroke. The
      question "Have you ever had a stroke?" had a sensitivity of 95% and a specificity
      of 96%. CONCLUSIONS: This simple self-completion questionnaire is a valid means
      of screening for cases of stroke in the community and could form the basis for
      subsequent studies of prevalence and health needs.

PMID- 7631333
TI  - Inadequacy of clinical scoring systems to differentiate stroke subtypes in
      population-based studies.
AB  - BACKGROUND AND PURPOSE: We undertook to examine the usefulness for
      epidemiological studies of two well-known validated clinical scoring methods, the
      Guys' Hospital Stroke score and the Siriraj Hospital Stroke score, to classify
      strokes into the two main types, hemorrhagic and ischemic, in epidemiological
      studies. METHODS: Patients from a population-based stroke register who received
      either a CT scan or an autopsy were retrospectively scored using the two clinical
      scoring methods. The scores were then compared with the CT scan and autopsy
      results to determine the sensitivity, specificity, and positive predictive value
      for intracranial hemorrhage (primary intracerebral and subarachnoid hemorrhage)
      and ischemic stroke. RESULTS: Over a 12-month period, 554 patients from a
      population-based study underwent CT scanning. Films or autopsy reports were
      available for 521 patients, and of these, sufficient clinical information to
      calculate the Guys' Hospital Stroke score and the Siriraj Hospital Stroke score
      was available for 464 and 475 patients, respectively. For the Guys' Hospital
      Stroke score, the sensitivity and specificity for intracranial hemorrhage were
      31% and 95%, respectively; the positive predictive value was 73%. The sensitivity
      and specificity for ischemic stroke were 78% and 70%, respectively, and the
      positive predictive value was 86%. For the Siriraj Hospital Stroke score, the
      sensitivity and the specificity for intracranial hemorrhage were 48% and 85%,
      respectively; the positive predictive value was 59%. The sensitivity and
      specificity for ischemic stroke were 61% and 74%, respectively, and the positive
      predictive value was 84%. CONCLUSIONS: This validation study suggests that both
      clinical scores lack sufficient validity to be used in epidemiological studies
      for classification of stroke types and should probably not be used in the
      randomization of patients into treatment trials using thrombolytic or
      antithrombotic drugs in the absence of diagnostic information based on
      neuroimaging techniques.

PMID- 7631334
TI  - Temporal patterns of stroke onset. The Framingham Study.
AB  - BACKGROUND AND PURPOSE: Several studies have shown stroke onset to vary by
      season, day of the week, and time of day. These temporal patterns, which may
      provide insights into pathogenesis, were found mainly in clinical series, which
      can be subject to selection bias. To obtain a less distorted picture of stroke
      onset, we examined the month and season, day of the week, time, and place stroke
      occurred in a community-based cohort. METHODS: Over a 40-year period of
      surveillance of the Framingham Study cohort of 5070 people aged 30 to 62 years
      and free of stroke and cardiovascular disease at entry, 637 completed initial
      strokes occurred. Month, season, day of the week, time of day, and place of
      occurrence of stroke were ascertained systematically and related prospectively to
      stroke incidence, subtype, and gender. RESULTS: Winter was the peak season for
      cerebral embolic strokes. Significantly more stroke events occurred on Mondays
      than any other day, particularly for working men. For intracerebral hemorrhages,
      a third happened on Mondays in both genders. The time of day when strokes most
      frequently occurred was between 8 AM and noon. This pattern was true for all
      stroke subtypes. This pattern persisted when individuals whose onset occurred
      while sleeping or on awakening were excluded. Stroke in general occurred more at
      home, with hemorrhagic strokes occurring outside the home and cerebral embolisms
      in the hospital more than other subtypes. CONCLUSIONS: Temporal patterns of
      stroke onset were observed for season, day of the week, time of day, and place in
      a community-based population. These findings suggest that there are periods of
      increased risk of stroke that may be amenable to preventive strategies.

PMID- 7631335
TI  - Silent brain infarcts and transient ischemic attacks. A three-year study of first
      ever ischemic stroke patients: the Klosterneuburg Stroke Data Bank.
AB  - BACKGROUND AND PURPOSE: We undertook to study the clinical relevance of silent
      strokes and history of transient ischemic attacks (TIAs) and their individual and
      combined effects on outcome variables of neurological and epidemiological
      interest in first-ever stroke patients. METHODS: We performed univariate and
      multivariate analyses of data prospectively collected in the Klosterneuburg
      Stroke Data Bank, a hospital-based registry in Austria that includes a 3-year
      follow-up program. RESULTS: Of 728 patients (mean age, 68 +/- 10 years) with a
      first-ever ischemic stroke, 110 (15%) had had a previous TIA, and 66/618 (11%)
      patients did not have a history of TIA but showed evidence of silent brain
      infarct on CT. Outcome variables of neurological interest were not significantly
      different between groups, including time between stroke and study entry,
      activities of daily living status at first presentation, median time of
      hospitalization, 30-day mortality, or 3-year mortality. Univariate analyses of
      epidemiologically important risk factors showed either history of TIA or evidence
      of silent infarct to be more frequently associated with hypertension (P = .007).
      Cox models of survival showed that neither history of TIA nor evidence of silent
      infarct were significantly associated with an increase in 3-year mortality.
      CONCLUSIONS: Over a period of 3 years, neither history of TIA nor evidence of
      silent infarct diagnosed at the time of the presenting major stroke in first-ever
      ischemic stroke patients exert an important influence on neurological or
      epidemiological outcome variables.

PMID- 7631336
TI  - Effects of a specialized team on stroke care. The first two years of the Yale
      Stroke Program.
AB  - BACKGROUND AND PURPOSE: Strategies have been proposed for stroke care to improve
      quality or reduce cost. We sought to document the effects of a new program of
      specialized stroke care. METHODS: In a programmatic review using historical and
      concurrent control subjects, we evaluated patients discharged with a stroke
      diagnosis (diagnosis-related group 14) over a 6-year period between January 1987
      and December 1992. Patients were from an academic medical center. The
      intervention was consultation (on university neurology patients) by a specialized
      multidisciplinary team during the last 2 years of the review period. The main
      outcome measures were median length of stay and rate of common complications
      before and after implementation compared with other hospital services (private
      neurology and medicine). RESULTS: Stroke team involvement was associated with a
      shortened median length of stay from 10 to 8 days (P < .0001). There was no
      significant change in the median length of stay for the private neurology or
      medicine services. After stroke team involvement, there were fewer urinary tract
      infections (P = .056), and those patients who developed infection had a shorter
      length of stay (P = .0007). There was no change in the rate of aspiration
      pneumonia or in length of stay for patients with aspiration pneumonia. Mortality
      did not change. CONCLUSIONS: A coordinated, multidisciplinary approach to stroke
      care may reduce length of stay and morbidity in patients hospitalized because of
      stroke.

PMID- 7631337
TI  - Spontaneous early improvement following ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Recognizing that early spontaneous neurological
      improvement not uncommonly follows acute ischemic stroke, we conducted this study
      to determine the incidence of such improvement and its potential relation to
      stroke etiology. METHODS: We prospectively evaluated 68 patients who presented
      within 12 hours after ischemic stroke, exhibited moderate or severe new
      functional neurological deficit acutely, and received either no stroke-specific
      therapy or only antiplatelet therapy over the ensuring week. We reexamined all
      patients 1 week after stroke onset. RESULTS: Sixteen (24%) of the 68 patients
      improved to the point of having no or mild functional neurological deficit at 1
      week. Patients with lacunar stroke were more likely to enjoy early spontaneous
      improvement (8/22 = 36% versus 8/46 = 17%), but this difference did not reach
      statistical significance (P = .15). CONCLUSIONS: Early spontaneous improvement
      after ischemic stroke may occur in a substantial proportion of patients and more
      commonly after lacunar stroke. Even so, the majority of patients with acutely
      disabling stroke will remain significantly impaired 1 week after stroke onset.

PMID- 7631338
TI  - Platelet activation is not involved in acceleration of the coagulation system in
      acute cardioembolic stroke with nonvalvular atrial fibrillation.
AB  - BACKGROUND AND PURPOSE: It is generally accepted that the coagulation system is
      activated in ischemic stroke and that platelet activation is involved in the
      pathogenesis of this disease. However, little is known about how and to what
      extent platelet activity participates in coagulation system enhancement. We
      evaluated the hemostatic condition, especially with regard to platelet function
      and the coagulation system, within 3 days of onset of acute stroke. The study
      participants were limited to elderly patients with cardioembolic stroke due to
      nonvalvular atrial fibrillation. METHODS: Seventeen elderly patients with acute
      cardioembolic stroke due to nonvalvular atrial fibrillation were investigated.
      Within 3 days of stroke onset, beta-thromboglobulin (BTG), platelet factor 4
      (PF4), thrombin-antithrombin III complex (TAT), and D-dimer from arterial blood
      were carefully evaluated in these patients. Blood samples from 19 healthy age-
      and sex-matched control subjects were also examined. RESULTS: The two studied
      markers of platelet activity did not change in the patients or the control
      subjects, and the between-group differences between the stroke and control groups
      were not statistically significant (BTG, 43.8 versus 31.9 ng/mL; PF4, 9.06 versus
      5.78 ng/mL; respectively). In contrast, the two studied coagulation-system
      indicators were markedly elevated in the patients compared with the control
      subjects (TAT, 13.8 versus 3.5 ng/mL, P < .01; D-dimer, 366.3 versus 147.2 ng/mL,
      P < .01; respectively). CONCLUSIONS: Platelet function was not enhanced in the
      acute stage of cardioembolic stroke with nonvalvular atrial fibrillation. This
      result indicates that enhancement of the coagulation system in cardioembolic
      stroke is not the result of platelet hyperfunction, ie, "platelet-fibrin"
      thrombi, but rather of "stasis-related" thrombi formation.

PMID- 7631339
TI  - Hyperbaric oxygen in the treatment of acute ischemic stroke. A double-blind pilot
      study.
AB  - BACKGROUND AND PURPOSE: The effects of hyperbaric oxygen (HBO) therapy on humans
      are uncertain. Our study aims first to outline the practical aspects and the
      safety of HBO treatment and then to evaluate the effect of HBO on long-term
      disability. METHODS: Patients who experienced middle cerebral artery occlusion
      and were seen within 24 hours of onset were randomized to receive either active
      (HBO) or sham (air) treatment. The HBO patients were exposed daily to 40 minutes
      at 1.5 atmospheres absolute for a total of 10 dives. We used the Orgogozo scale
      to establish a pretreatment functional level. Changes in the Orgogozo scale score
      at 6 months and 1 year after therapy were used to assess the therapeutic efficacy
      of HBO. In addition, we used the Rankin scale and our own 10-point scale to
      assess long term-disability at 6 months and 1 year. Two sample t tests and 95%
      confidence intervals were used to compare the mean differences between the two
      treatment groups. Student's two-tailed test was used to compare the differences
      between pretherapeutic and posttherapeutic scores at 6 months and 1 year in the
      two treatment groups. RESULTS: Over the 3 years of study enrollment, 34 patients
      were randomized, 17 to hyperbaric treatment with air and 17 to hyperbaric
      treatment with 100% oxygen. There was no significant difference at inclusion
      between groups regarding age, time from stroke onset to randomization, and
      Orgogozo scale scores. Neurological deterioration occurred during the first week
      in 4 patients in the sham group, 3 of whom died; this worsening was clearly
      related to the ischemic damage. Treatment was also discontinued for 3 patients in
      the HBO group who experienced myocardial infarction, a worsening related to the
      ischemic process, and claustrophobia. Therefore, 27 patients (13 in the sham
      group and 14 in the HBO group) completed a full course of therapy. The mean score
      of the HBO group was significantly better on the Orgogozo scale at 1 year (P <
      .02). However, the difference at 1 year between pretherapeutic and
      posttherapeutic scores was not significantly different in the two groups (P <
      .16). Moreover, no statistically significant improvement was observed in the HBO
      group at 6 months and 1 year according to Rankin score (P < .78) and our own 10
      point scale (P < .50). CONCLUSIONS: Although the small number of patients in each
      group precludes any conclusion regarding the potential deleterious effect of HBO,
      we did not observe the major side effects usually related to HBO. Accordingly, it
      can be assumed that hyperbaric oxygen might be safe. We hypothesize that HBO
      might improve outcome after stroke, as we detected an outcome trend favoring HBO
      therapy. A large randomized trial might be required to address the efficacy of
      this therapy.

PMID- 7631340
TI  - Nocturnal blood pressure dip in stroke survivors. A pilot study.
AB  - BACKGROUND AND PURPOSE: The influence of a nocturnal blood pressure dip on stroke
      recurrence has not yet been clarified. In this pilot study, we attempted to
      establish a correlation of the nocturnal blood pressure dip with stroke
      recurrence and development of new silent ischemic lesions in patients with
      chronic ischemic cerebrovascular disease. METHODS: We monitored circadian blood
      pressure patterns by use of a portable blood pressure monitoring device in 81
      patients with chronic ischemic cerebrovascular disease and divided them into two
      subgroups according to levels of diurnal and nocturnal blood pressure (nocturnal
      blood pressure dippers and nondippers). The subgroups were prospectively followed
      up and compared for stroke recurrence and new silent ischemic lesions on magnetic
      resonance imaging. RESULTS: The average follow-up period was 27.2 +/- 11.3 months
      (mean +/- SD). Seventy-six patients completed the study; 43 (36 men and 7 women,
      aged 63.0 +/- 6.3 years) were being treated with antihypertensive agents and 33
      (25 men and 8 women, aged 64.7 +/- 9.2 years) were not receiving treatment. In
      the treated group, recurrence was more frequent among the nocturnal dippers (5 of
      18 patients, 12.5% per patient-year) than among the nondippers (1 of 25 patients,
      1.5% per patient-year) (P < .05). All subjects who developed a recurrent attack
      during sleep had had a nocturnal blood pressure dip pattern before the attack.
      Furthermore, the increase in symptomatic (recurrence) and/or asymptomatic
      (silent) brain lesions was more frequent in the nocturnal dippers than in the
      nondippers (9 of 14 versus 2 of 18, P < .01). In the nontreated group, no clear
      difference was found between the two subgroups. CONCLUSIONS: This study indicated
      that the nocturnal blood pressure dip in patients treated with antihypertensive
      agents may accelerate the increase in ischemic brain lesions.

PMID- 7631341
TI  - Autonomic and thermal sensory symptoms and dysfunction after stroke.
AB  - BACKGROUND AND PURPOSE: Symptoms interpreted as unilateral disturbances of
      autonomic function, such as coldness, dryness, sweating, and trophic changes, are
      well known but incompletely understood clinical problems after stroke. The
      present study provides data related to the incidence and mechanisms behind such
      symptoms. METHODS: Temperature perception thresholds, skin temperatures,
      evaporation rates, and skin blood flow responses were measured bilaterally in 37
      stroke patients aged 58 +/- 13 years (mean +/- SD) and in a control group of 15
      patients aged 64 +/- 15 years with a single transient ischemic attack. RESULTS:
      Of the 37 stroke patients, 43% reported a sensation of coldness in the
      contralesional side of the body. Basal skin blood flow and temperature were
      relatively lower in the contralesional side. There was an excess of evaporation
      in the contralesional side after brain stem lesions and in the ipsilesional side
      after hemispheric lesions. Vasomotor reflex asymmetries occurred in 34% of the
      patients and were due to weak vasodilator or vasoconstrictor reflexes in the
      ipsilesional side. These abnormalities correlated significantly to sensations of
      unilateral coldness, hypalgesia, and thermohypesthesia in the contralesional side
      and anatomically to lesions in spinothalamo-cortical pathways. CONCLUSIONS: Focal
      central nervous system lesions due to stroke may result in symptoms and
      measurable evidence of unilateral disturbance of skin sympathetic function.
      Vasomotor asymmetries are probably due to lesions of vasomotor pathways
      descending uncrossed. Subjective coldness may be due to disturbed central
      processing.

PMID- 7631342
TI  - Effects of the valsalva maneuver on cerebral circulation in healthy adults. A
      transcranial Doppler Study.
AB  - BACKGROUND AND PURPOSE: Knowledge is limited about the effects of the Valsalva
      maneuver on cerebral circulation because of the poor temporal resolution of
      traditional cerebral blood flow measurements. The purpose of this study was to
      investigate changes in cerebral blood flow during the Valsalva maneuver and to
      explore its potential use for the evaluation of cerebral autoregulation. METHODS:
      Using transcranial Doppler ultrasonography, we simultaneously recorded systemic
      arterial blood pressure in the radial artery and flow velocities in both middle
      cerebral arteries in 10 healthy adults during the Valsalva maneuver. Gosling's
      pulsatility index was calculated for all phases of the Valsalva maneuver.
      Autoregulatory capacities were estimated from the change in cerebrovascular
      resistance (flow velocity in relationship to blood pressure) during phase II and
      changes in the velocity-pressure relationship in phase IV relative to phase I.
      RESULTS: The characteristic changes in blood pressure (phases I to IV) were seen
      in all subjects, accompanying distinct changes in cerebral blood flow velocity.
      The relative changes in mean velocity during phases II and IV were significantly
      greater than those in mean blood pressure. Compared with the baseline value,
      velocity decreased by 35% in phase IIa, then rose by 56.5% in phase IV
      (corresponding changes in blood pressure were -10.2% and +29.8%, respectively).
      During phase II, the pulsatility and cerebrovascular resistance decreased by
      19.9%. The increase in cerebral blood flow velocity in phase IV was significantly
      higher than in phase I (P < .0004), and there was no corresponding significant
      difference in blood pressure. CONCLUSIONS: These results demonstrated that in
      healthy humans the Valsalva maneuver causes characteristic changes in systemic
      blood pressure as well as in flow velocity in the middle cerebral artery,
      reflecting the sympathetic and cerebral autoregulatory responses, respectively.
      Analysis of these changes may provide an estimate of autoregulatory capacity.

PMID- 7631343
TI  - Early intrathecal production of interleukin-6 predicts the size of brain lesion
      in stroke.
AB  - BACKGROUND AND PURPOSE: We have previously demonstrated that stroke influences
      systemic immune responses. The aim of the present study was to investigate
      patterns of local inflammatory response as a consequence of acute stroke.
      METHODS: Thirty stroke patients were studied prospectively on days 0 to 3, 7 to
      9, 21 to 26, and after day 90 with clinical evaluations, radiological
      assessments, and analysis of serum and cerebrospinal fluid cytokine levels.
      RESULTS: Significantly increased levels of interleukin-6 (IL-6) in cerebrospinal
      fluid (P < .001) were observed in virtually all patients studied compared with
      healthy control subjects. This increase was observed during the whole observation
      period but was significantly more pronounced within the first days after stroke
      onset, with a peak level on days 2 and 3. This initial increase was significantly
      correlated (r = .65, P = .002) with the volume of infarct measured by MRI 2 to 3
      months later. Serum levels of IL-6 in stroke patients were significantly lower
      than cerebrospinal fluid levels of IL-6 (P = .013) and did not display any
      significant correlation to the size of the brain lesion. Also, increase in
      intrathecal but not systemic production of IL-1 beta was observed early during
      the stroke. Only minor increases of cerebrospinal fluid interferon-gamma levels
      were observed in two patients. CONCLUSIONS: Our study demonstrates an intrathecal
      production of IL-6 and IL-1 beta in patients with stroke, supporting the notion
      of localized inflammatory response to acute brain lesion. In addition, the
      significant correlation between early intrathecal production of IL-6 and the
      subsequent size of the brain lesion can be used as a prognostic tool, predicting
      the size of the brain damage before it is possible to accurately visualize it
      with radiological methods.

PMID- 7631345
TI  - Cerebral blood flow in lateral medullary infarcts.
AB  - BACKGROUND AND PURPOSE: The aim of this study was to evaluate the diaschisis
      phenomenon in patients presenting with lateral medullary infarct (Wallenberg's
      syndrome). METHODS: We examined all patients admitted between 1991 and 1993. The
      localization of lesions was evaluated by MRI. Single-photon emission computed
      tomographic technique was used to assess cerebral blood flow by two methods
      (133Xe and hexamethylpropyleneamine oxime) on five slices of brain tissue. Flow
      values were calculated in 11 regions of interest in each cerebral hemisphere and
      in the cerebellum and were compared with those obtained in 20 control subjects.
      RESULTS: Three patients had selective lateral medullary infarct: Relative
      reduction of flow (133Xe) and of tracer uptake (HMPAO) were observed in one
      patient in the ipsilateral cerebellum and contralateral hemisphere; in two
      patients, hemispheric flow values were relatively low, without significant
      asymmetry. Two patients also presented with cerebellar infarct: Flow drop was
      severe in the ipsilateral cerebellum, and contralateral reduction in the brain
      hemisphere was observed in both cases. CONCLUSIONS: Lateral medullary infarct can
      be associated with ipsilateral reduction of flow in the cerebellum, but this
      phenomenon is inconstant. Severe flow drop suggests infarction in the territory
      of the posterior inferior cerebellar artery. Contralateral hemispheric flow
      reduction can also be observed. These phenomena of cerebellar and crossed
      hemispheric diaschisis are probably related to lesions of tracts from the olivary
      and reticular nuclei.

PMID- 7631344
TI  - Clinical relevance and frequency of transient stenoses of the middle and anterior
      cerebral arteries in bacterial meningitis.
AB  - BACKGROUND AND PURPOSE: We sought to examine the frequency and clinical relevance
      of intracranial artery stenoses in patients with bacterial meningitis in whom the
      occurrence of stroke has angiographically been reported to be associated with
      stenoses or occlusions of the large basal cerebral arteries. METHODS: Thirty-five
      unselected patients (24 men, 11 women; mean age, 51 +/- 18 years) with bacterial
      (n = 33) or fungal (n = 2) meningitis prospectively underwent serial transcranial
      Doppler sonography recordings of mean blood velocity (MBV) and pulsatility index
      in the middle (MCA) and anterior (ACA) cerebral arteries, as well as recordings
      of the ratio of the MBV of the MCA and internal carotid artery (MCA/ICA ratio) on
      days 1, 3, 5, 8, 14, and 21 after admission. The results were correlated with the
      Glasgow Coma Scale (days 1 to 14), the occurrence of focal cerebral signs, and
      the Glasgow Outcome Scale (short-term outcome, day 21). An MCA stenosis was
      diagnosed by an MBV of 120 cm/s or more or an MCA/ICA ratio of more than 3. An
      ACA stenosis was diagnosed by an MBV of 100 cm/s or more. RESULTS: Transient
      stenoses occurred most frequently between days 3 and 5 and were detected in 18
      patients (51%). Seventeen patients remained without a stenosis. Patients with
      stenoses showed a significantly poorer mean Glasgow Coma Scale score from day 3
      (9 +/- 4) to day 14 (11 +/- 4) than patients without a stenosis (day 3: 13 +/- 4,
      P < .01 by t test; day 14: 14 +/- 1, P < .05). The mean Glasgow Outcome Scale
      score was not significantly different between both groups. The occurrence of
      mainly transient focal cerebral signs was significantly related to the number of
      narrowed vessels per patient (P < .05, chi 2 test). CONCLUSIONS: Stenoses of the
      intracranial arteries occur frequently in bacterial meningitis and are associated
      with a complicated course of the disease.

PMID- 7631346
TI  - Cigarette smoking accelerates carotid artery intimal hyperplasia in a dose
      dependent manner.
AB  - BACKGROUND AND PURPOSE: Intimal hyperplasia is the single most important cause of
      early restenosis after carotid endarterectomy. Cigarette smoking is an
      independent risk factor associated with peripheral vascular disease and
      cerebrovascular accidents. We undertook a dose-response experiment to determine
      the effect of cigarette smoke on development of intimal hyperplasia in a rat
      carotid artery intimal injury model. METHODS: Seventy-two rats were divided into
      six equal groups and underwent standardized balloon injury to the carotid artery.
      Each group received 0 (controls), 1, 2, 3, 6, or 8 cigarettes per day for 4
      weeks. Resultant intimal hyperplasia was expressed as a percentage of original
      lumen replaced by intimal hyperplasia. RESULTS: Percent intimal hyperplasia
      development (+/- SD) was as follows: controls (0 cigarettes per day), 17.7 +/-
      13.2; 1 cigarette per day, 22.8 +/- 15.0; 2 cigarettes per day, 20.0 +/- 14.7; 3
      cigarettes per day, 19.2 +/- 12.1; 6 cigarettes per day, 43.5 +/- 15.5; and 8
      cigarettes per day, 36.7 +/- 9.8. Six and 8 cigarettes per day significantly
      increased the development of intimal hyperplasia after intimal injury (P < .01).
      CONCLUSIONS: High-dose cigarette smoke accelerates development of intimal
      hyperplasia and may pose a significant risk factor in developing carotid
      restenosis.

PMID- 7631347
TI  - Protective effect of cyclosporin A on white matter changes in the rat brain after
      chronic cerebral hypoperfusion.
AB  - BACKGROUND AND PURPOSE: Activation of glial cells and rarefaction of the white
      matter have been reported in rat brain after bilateral permanent occlusion of the
      common carotid arteries. Using this model, we investigated the effects of the
      immunosuppressant cyclosporin A on the activation of glial cells and the white
      matter rarefaction. METHODS: Both common carotid arteries were ligated
      bilaterally in 40 male Wistar rats. Twenty-two of these rats received an
      intraperitoneal injection of cyclosporin A, and the remaining 18 received a
      vehicle-solution injection. Microglia/macrophages were investigated with
      immunohistochemistry for the major histocompatibility complex class I and II
      antigens as well as for leukocyte common antigen. Astroglia were examined with
      glial fibrillary acidic protein as a marker. Activation of glial cells and white
      matter rarefaction were then investigated from 7 to 30 days after the ligation.
      RESULTS: In vehicle-treated animals, there was a persistent and extensive
      activation of both microglia/macrophages and astroglia in the white matter,
      including the optic nerve, optic tract, corpus callosum, internal capsule, and
      traversing fiber bundles of the caudoputamen. In cyclosporin A-treated rats, the
      number of activated microglia/macrophages was significantly reduced (P < .01) to
      approximately one fifth of that in vehicle-treated animals. Similarly,
      rarefaction of the white matter was much less intense in cyclosporin A-treated
      rats (P < .01). CONCLUSIONS: Cyclosporin A suppressed both glial activation and
      white matter changes after chronic cerebral hypoperfusion. These results suggest
      that immunologic reaction may play a role in the pathogenesis of the white matter
      changes and that the present model may be useful in investigating the
      pathophysiology of white matter changes induced by chronic cerebral
      hypoperfusion.

PMID- 7631348
TI  - Cerebral protection against ischemia by locomotor activity in gerbils. Underlying
      mechanisms.
AB  - BACKGROUND AND PURPOSE: A previous communication of this laboratory demonstrated
      reduced mortality and neuronal damage by spontaneous locomotor activity preceding
      forebrain ischemia in Mongolian gerbils. The present experiments seek to
      elucidate potential mechanisms of protection by measurement of cerebral blood
      flow, cerebral tissue conductance as an indicator of ischemic cell swelling, and
      the cerebral release of eicosanoids. METHODS: Gerbils were maintained either in
      conventional cages (nonrunners) or with free access to running wheels (runners)
      for 2 weeks preceding 15 minutes of forebrain ischemia. During ischemia and 2.5
      hours of reperfusion, cerebral tissue conductance was determined with a two
      electrode system. Simultaneously, prostaglandin D2, prostaglandin F2 alpha, and
      thromboxane B2 were measured in ventriculocisternal perfusate. In additional
      animals cerebral blood flow was assessed by hydrogen clearance. RESULTS:
      Decreases in tissue conductance during ischemia were similar in nonrunners (56 +/
      3%) and runners (62 +/- 3%) but normalized more rapidly in runners during
      reperfusion. In both groups reperfusion was accompanied by marked increases of
      perfusate prostaglandin D2, prostaglandin F2 alpha, and thromboxane B2. In
      nonrunners, however, thromboxane B2 was already elevated during ischemia (147 +/-
      9%, P < .01) and remained elevated longer during recirculation (P < .05).
      Postischemic perfusion maxima were higher in runners (70.8 +/- 7.4 versus 47.0 +/
      5.0 mL/100 g per minute, P < .05) and were observed sooner (27.4 +/- 6.9 versus
      62.2 +/- 12.3 minutes, P < .05). Both groups displayed delayed hypoperfusion of a
      similar magnitude (runners, 29.0 +/- 2.4 mL/100 g per minute; nonrunners, 30.1 +/
      2.4 mL/100 g per minute). CONCLUSIONS: Protection by preischemic locomotor
      activity may involve enhanced postischemic reperfusion, leading to more rapid
      normalization of conductance and thus of cell volume. Enhanced reperfusion may be
      the consequence of attenuated thromboxane liberation during and after ischemia.

PMID- 7631349
TI  - Circulation of red blood cells having high levels of 2,3-bisphosphoglycerate
      protects rat brain from ischemic metabolic changes during hemodilution.
AB  - BACKGROUND AND PURPOSE: We designed the present study to examine the effects of
      red blood cell oxygen-delivering capacity on ischemic brain metabolism during
      hemodilution with respect to red blood cell 2,3-bisphosphoglycerate content.
      METHODS: A modification of red blood cell 2,3-bisphosphoglycerate content was
      achieved by an exchange transfusion of blood in which red blood cells were
      treated with either phospho(enol)pyruvate or inorganic phosphate in spontaneously
      hypertensive rats. Hematocrit values of circulating blood were varied from 30% to
      20% during transfusion. Brain ischemia was produced in rats by bilateral carotid
      artery occlusion lasting 60 minutes. The concentrations of ATP and 2,3
      bisphosphoglycerate in the blood and the ATP, phosphocreatine, and lactate
      concentrations in the brain were estimated by an enzymatic method. RESULTS: Red
      blood cell 2,3-bisphosphoglycerate concentration increased to 200% of the
      pretransfusion level after the transfusion in which red blood cells were treated
      with phospho(enol)pyruvate, whereas the concentration decreased to 80% after the
      transfusion in which red blood cells were treated with phosphate. Red blood cell
      ATP content did not differ significantly between the phospho(enol)pyruvate- and
      phosphate-treated groups after transfusion. When hematocrit was approximately
      30%, the ischemic brain ATP and lactate contents did not differ between the
      nonischemic and ischemic groups. However, as hematocrit was reduced to less than
      25% the ischemic brain ATP content remarkably decreased and the lactate content
      substantially increased in the 2,3-bisphosphoglycerate-subnormal red blood cell
      group. In contrast, the ischemic brain ATP and phosphocreatine contents in the
      2,3-bisphosphoglycerate-enriched red blood cell group were preserved and as high
      as those in the nonischemic group under the same conditions. CONCLUSIONS:
      Cerebral ischemia was compensated with the increment of cerebral blood flow as a
      result of the reduction of hematocrit to optimal levels, but the extreme
      hemodilution induced insufficient oxygen supply to the brain tissue, resulting in
      a more marked impairment of brain metabolism despite an increase in cerebral
      blood flow. However, even in extreme hemodilution conditions the 2,3
      bisphosphoglycerate-enriched red blood cells in circulating blood protected the
      brain from ischemic metabolic changes. These results suggest that the 2,3
      bisphosphoglycerate-enriched red blood cells in the circulating blood may thus
      compensate for the insufficient oxygen supply in extremely anemic conditions by
      providing a sufficient supply of oxygen in the face of ischemic insult.

PMID- 7631350
TI  - Anti-intercellular adhesion molecule-1 antibody reduces ischemic cell damage
      after transient but not permanent middle cerebral artery occlusion in the Wistar
      rat.
AB  - BACKGROUND AND PURPOSE: Postischemic cerebral inflammation may contribute to
      ischemic cell damage. Intercellular adhesion molecule-1 (ICAM-1) is a
      glycoprotein expressed on endothelial cells that facilitates leukocyte adhesion.
      We investigated the effect of administration of an anti-ICAM-1 antibody (1A29) on
      ischemic cell damage after transient (2-hour) or permanent middle cerebral artery
      (MCA) occlusion in the Wistar rat. METHODS: Groups studied were as follows: (1)
      transient MCA occlusion: rats were subjected to 2 hours of MCA occlusion, and
      after 1 hour of reperfusion they were treated with 1A29 (n = 11) or an isotype
      control antibody (n = 9); and (2) permanent MCA occlusion: rats were treated with
      1A29 (n = 9) or an isotype control antibody (n = 7) 2 hours after onset of MCA
      occlusion. All animals were killed 1 week after onset of ischemia. Brain sections
      were stained with hematoxylin and eosin for histological evaluation. RESULTS:
      Significant reductions (P < .05) in both volume (44%) of the ischemic lesion and
      weight loss were found in animals subjected to transient MCA occlusion and
      treated with 1A29 compared with vehicle-treated animals. In contrast, in animals
      subjected to permanent MCA occlusion the lesion and the temporal profile of body
      weight were not altered by 1A29 administration. CONCLUSIONS: Ischemic cell damage
      is promoted by postischemic inflammatory response after 2 hours of transient MCA
      occlusion, and ischemic cell damage is reduced by administration of an anti-ICAM
      1 antibody during reperfusion.

PMID- 7631351
TI  - Effects of intermittent reperfusion on brain pHi, rCBF, and NADH during rabbit
      focal cerebral ischemia.
AB  - BACKGROUND AND PURPOSE: The use of intermittent reperfusion versus straight
      occlusion during neurovascular procedures is controversial. This experiment
      studied the effects of intermittent reperfusion and single occlusion on
      intracellular brain pH (pHi), regional cerebral or cortical blood flow, and
      nicotinamide adenine dinucleotide (NADH) fluorescence during temporary focal
      ischemia. METHODS: Twenty fasted rabbits under 1.0% halothane anesthesia were
      divided into four groups: (1) nonischemic controls, (2) 60 minutes of
      uninterrupted focal ischemia, (3) 2 x 30-minute periods of focal ischemia
      separated by a 5-minute reperfusion, and (4) 4 x 15-minute periods of focal
      ischemia separated by three 5-minute reperfusion periods. Focal ischemia was
      produced by occlusion of both the middle cerebral and ipsilateral anterior
      cerebral arteries. After the final occlusion, there was a 3-hour reperfusion
      period in all groups. Regional cerebral and cortical blood flow, brain pHi, and
      NADH fluorescence were measured with in vivo panoramic fluorescence imaging.
      RESULTS: During occlusion, regional cerebral and cortical blood flows and NADH
      fluorescence values were not different among the groups. Brain pHi was
      significantly lower in the 4 x 15-minute group compared with the 1 x 60-minute
      group (6.57 +/- 0.02 versus 6.73 +/- 0.06; P < .03) but not significant when
      compared with the 2 x 30-minute group. During the short reperfusion periods, all
      parameters returned to normal except for NADH fluorescence levels, which remained
      elevated. During the postischemic final reperfusion period, there was a mild
      brain alkalosis of approximately 7.1 in all groups. There were no significant
      differences in NADH fluorescence among groups during the final reperfusion.
      Regional cerebral and cortical blood flow returned to near normal values in all
      groups. CONCLUSIONS: This study demonstrates that intermittent reperfusion during
      temporary focal ischemia has different effects on the intracytoplasmic and the
      intramitochondrial compartments: worsening of brain cytoplasmic pHi but no
      significant differences in the oxidation/reduction level of mitochondrial NADH.

PMID- 7631352
TI  - Perfusion and diffusion-weighted MR imaging for in vivo evaluation of treatment
      with U74389G in a rat stroke model.
AB  - BACKGROUND AND PURPOSE: The present study was performed to examine the potential
      of diffusion-weighted (DW) imaging and dynamic first-passage bolus tracking of
      susceptibility contrast agents (perfusion imaging) for early in vivo evaluation
      of the effects of treatment with the free radical scavenger U74389G in a rat
      model of temporary focal ischemia. METHODS: After 45 minutes of middle cerebral
      artery occlusion, the treatment group (n = 9) received an infusion of U74389G,
      and the control group (n = 9) received the identical volume of the vehicle.
      Reperfusion was instituted in both groups after 120 minutes of middle cerebral
      artery occlusion. The DW images were collected during middle cerebral artery
      occlusion and reperfusion and were compared with histologically assessed areas of
      tissue injury after 2 hours of reperfusion. The dynamic perfusion series were
      processed on a pixel-to-pixel basis to produce parametric maps reflecting the
      maximum reduction in the signal obtained during the first passage of the contrast
      agent and the time delay between the arrival of the bolus and the point of
      maximum contrast-agent effect. RESULTS: The area of ischemic injury, as assessed
      from the DW imaging at 60 minutes of reperfusion, was significantly smaller in
      the treatment group: 9 +/- 8% of ipsilateral hemisphere compared with 19 +/- 8%
      in the control group. The histological examination after 2 hours of reperfusion
      demonstrated an area of ischemic injury of 10 +/- 8% for the treatment group
      compared to 25 +/- 10% in the control group. In the treatment group, the
      perfusion imaging showed a reduction in time delay to maximum effect of the
      contrast agent in the ischemic hemisphere compared with the control group.
      CONCLUSIONS: The DW imaging during early reperfusion showed a protective effect
      of postocclusion treatment with the free radical scavenger U74389G. The
      improvement of time delay to maximum effect of the contrast agent observed in the
      perfusion imaging of the treatment group may reflect an improvement in the
      collateral flow to the ischemic tissue.

PMID- 7631353
TI  - Ministrokes in rat barrel cortex.
AB  - BACKGROUND AND PURPOSE: Many stroke models in rats are based on occlusion of the
      middle cerebral artery, which supplies a significant portion of multifunctional
      cortical and deep structures in the cerebral hemisphere. The purpose of this
      study was to develop a model for direct observation in real time of blood flow in
      and around focal ischemic regions of the cortex of known function. METHODS:
      Cranial windows were placed over the parietal cortex of adult Wistar and Sprague
      Dawley rats anesthetized with ketamine and xylazine. Whisker barrel cortex
      responding to stimulation of the contralateral whiskers was identified by an
      intrinsic optical signal. Transits of vital dyes were recorded by videomicroscopy
      before and after ligation of three to six branches and major collaterals of the
      middle cerebral artery through the dura. Infarcts were demonstrated with
      triphenyl-tetrazolium chloride staining; their relation to barrel cortex was
      determined by Nissl and cytochrome oxidase histology. RESULTS: Reduced blood flow
      in small ischemic regions was outlined by patient blue violet in the surrounding
      nonischemic area; arteriovenous latencies increased more than four times in
      ischemic cortex. Infarcts,typically 3 mm or less, were seen at 24 hours in 8 of
      16 Wistar and 9 of 9 Sprague-Dawley rats. The ministrokes were confirmed by
      histology to be in the somatosensory cortex. CONCLUSIONS: This model of local
      ischemia, produced deliberately in the functionally defined barrel cortex in
      rats, leads to ministrokes. Changes can be followed by videomicroscopy as they
      develop, and processes of recovery can potentially be monitored. Infarcts are
      confirmed by histology for their location and extent in the somatic
      representation.

PMID- 7631354
TI  - Ischemic stroke as first manifestation of essential thrombocythemia. Report of
      six cases.
AB  - BACKGROUND: Ischemic stroke as a presenting sign of essential thrombocythemia has
      been infrequently reported. We describe six patients in whom cerebrovascular
      disease was the first manifestation of this myeloproliferative disease. A
      positive endogenous megakaryocyte and/or erythroid colony growth from blood was a
      diagnostic criterion of essential thrombocythemia in patients with platelets
      counts lower than 600 x 10(9)/L. CASE DESCRIPTIONS: These six patients
      represented 0.54% of all patients with first stroke, 42.8% of all hematologic
      disorders associated with stroke, and 12.5% of all patients with essential
      thrombocythemia diagnosed from 1986 to 1992 at our institution. Eleven acute
      cerebrovascular accidents (6 transient ischemic attacks, 5 definitive cerebral
      infarcts) were registered. Mean time from ischemic stroke to diagnosis of
      essential thrombocythemia was 4.5 months (range, 1 to 12 months). The mean
      platelet count was 597 x 10(9)/L (range, 414 to 760 x 10(9)/L). Four patients had
      platelets counts lower than 600 x 10(9)/L. All patients had circulating erythroid
      progenitors, megakaryocytic progenitors, or both. CONCLUSIONS: Ischemic stroke as
      a presenting manifestation of essential thrombocythemia is probably
      underrecognized. The diagnosis of thrombocythemia should not be excluded on the
      basis of platelet counts lower than 600 x 10(9)/L. The availability of in vitro
      culture of hematopoietic progenitors from peripheral blood makes it possible to
      diagnose early and atypical cases.

PMID- 7631355
TI  - Vertical gaze palsies from medial thalamic infarctions without midbrain
      involvement.
AB  - BACKGROUND: Although the supranuclear pathways for vertical gaze control are not
      well defined, lesions of the mesencephalic reticular formation including the
      nucleus of Darkschewitsch, the rostral interstitial medial longitudinal
      fasciculus, the interstitial nucleus of Cajal, and the posterior commissure are
      known to produce vertical gaze palsies. MRI studies have not previously reported
      isolated thalamic lesions as the cause of vertical gaze palsies. CASE
      DESCRIPTIONS: Three patients with acute paralysis of vertical gaze were imaged
      with MRI. Sagittal T1 and axial T1, T2, and proton-weighted images were obtained.
      All three patients had repeated scans performed from 3 days to 6 weeks after the
      original study. Two patients exhibited unilateral right thalamic infarcts (polar
      and paramedial territory), and one patient had a bilateral paramedian thalamic
      infarction. There was no evidence of midbrain involvement on any of the images.
      CONCLUSIONS: Vertical gaze palsies are known to be produced by lesions of the
      rostral interstitial medial longitudinal fasciculus. This MRI study reveals
      thalamic infarctions without associated midbrain infarctions in three patients
      with vertical gaze palsies. This may be explained by interruption of supranuclear
      inputs.

PMID- 7631356
TI  - Oral anticoagulants and intracranial hemorrhage. Facts and hypotheses.
AB  - BACKGROUND: Intracranial hemorrhage is the most feared and lethal complication of
      oral anticoagulation. We review the frequency, predictors, and prognosis of this
      most common neurological complication of oral anticoagulation. SUMMARY OF REVIEW:
      Anticoagulation to conventional intensities increases the risk of intracranial
      hemorrhage 7- to 10-fold, to an absolute rate of nearly 1%/y for many stroke
      prone patients. Most (70%) anticoagulant-related intracranial hemorrhages are
      intracerebral hematomas (approximately 60% are fatal); the bulk of the remainder
      are subdural hematomas. Predictors of anticoagulant-related intracerebral
      hematoma are advanced patient age, prior ischemic stroke, hypertension, and
      intensity of anticoagulation. In approximately half of anticoagulated patients
      with intracerebral hematoma the bleeding evolves slowly over 12 to 24 hours, and
      emergency reversal of anticoagulation is crucial. CONCLUSION: Both patient
      factors and anticoagulation intensity importantly influence the rate of
      anticoagulation-related intracranial hemorrhage. Patient-related risk factors for
      this complication overlap with those for ischemic stroke. The risk/benefit
      equation of anticoagulation for elderly, stroke-prone patients is complex and
      differs from that for younger patients. The absolute rate reduction (not the
      relative risk reduction) of ischemic stroke by anticoagulation is the critical
      issue and must offset accentuation of often lethal brain hemorrhage.

PMID- 7631357
TI  - Ischemic delayed neuronal death. A mitochondrial hypothesis.
AB  - BACKGROUND: A brief period of global brain ischemia causes cell death in
      hippocampal CA1 pyramidal neurons days after reperfusion in rodents and humans.
      Other neurons are much less vulnerable. This phenomenon is commonly referred to
      as delayed neuronal death, but the cause has not been fully understood although
      many mechanisms have been proposed. SUMMARY OF REVIEW: Hippocampal CA1 neuronal
      death usually occurs 3 to 4 days after an initial ischemic insult. Such a delay
      is essential for the mechanism of this type of cell death. Previous hypotheses
      have not well explained the reason for the delay and the exact mechanism of the
      cell death, but a disturbance of mitochondrial gene expression could be a
      possibility. Reductions of mitochondrial RNA level and the activity of a
      mitochondrial protein, encoded partly by mitochondrial DNA, occurred exclusively
      in CA1 neurons at the early stage of reperfusion and were aggravated over time.
      In contrast, the activity of a nuclear DNA-encoded mitochondrial enzyme and the
      level of mitochondrial DNA remained intact in CA1 cells until death.
      Immunohistochemical staining for cytoplasmic dynein and kinesin, which are
      involved in the shuttle movement of mitochondria between cell body and the
      periphery, also showed early and progressive decreases after ischemia, and the
      decreases were found exclusively in the vulnerable CA1 subfield. CONCLUSIONS: A
      disturbance of mitochondrial DNA expression may be caused by dysfunction of the
      mitochondrial shuttle system and could cause progressive failure of energy
      production of CA1 neurons that eventually results in cell death. Thus, the
      mitochondrial hypothesis could provide a new and exciting potential for
      elucidating the mechanism of the delayed neuronal death of hippocampal CA1
      neurons.

PMID- 7631358
TI  - The Stroke Council of the American Heart Association. The early years.
AB  - An account of the origin, within the American Heart Association, of a council
      devoted to vascular disease of the central nervous system, with particular
      attention to the context in which that occurred, is presented in this article.
      The forces of a service-charitable organization, political action, medical
      practice in general, and interested, strong-witted citizens provided the stimuli
      for the development of the Stroke Council.

PMID- 7631359
TI  - Abscess complicating cerebral infarction.

PMID- 7631360
TI  - Brain abscess formation secondary to stroke.

PMID- 7631361
TI  - Brain abscess complicating ischemic stroke.

PMID- 7631362
TI  - Recent infection and cerebrovascular ischemia.

PMID- 7631363
TI  - Special issue: Suicide prevention toward the year 2000.

PMID- 7631364
TI  - The prevention of suicidal behaviors: an overview.
AB  - The authors discuss the development of the concept of prevention as it has
      evolved from the public health and mental health fields. Concepts of
      epidemiology, treatment, and community mental health are defined in terms of
      their contributions to the evolution of prevention thinking. Four models of
      prevention are presented and critiqued: the public health model, the operational
      model, the antecedent conditions model, and the injury control model. Essential
      ingredients for implementing effective preventive interventions are presented, as
      well as examples of practical preventive interventions.

PMID- 7631365
TI  - Suicide prevention in Canada: a national perspective highlighting progress and
      problems.

PMID- 7631366
TI  - Suicide prevention in an educational context: broad and narrow foci.
AB  - This paper reviews the needs and conceptual bases of school-based youth suicide
      prevention programs, summarizes their current status, and recommends objectives,
      processes, and evaluation strategies for focused educational programs in this
      area. In addition, a broad systemic approach is called for that reorganizes the
      school context to increase students' contributions, to and involvement with the
      educational process. Such approaches appear to have been effective with a variety
      of youth deviant behaviors such as dropout and delinquency, and seem to be
      particularly appropriate to suicidal behavior that is characterized by alienation
      and withdrawal from social supports. A combination of these broad and narrow foci
      may be necessary to address suicidal behavior in the educational context.

PMID- 7631367
TI  - Suicide prevention in a treatment setting.
AB  - Reducing the suicide rate through treatment depends on the development of new
      knowledge and new technology with emphasis on early intervention and continuing
      low-intensity contact for many troubled suicidal people, rather than the current
      preoccupation with detecting and hospitalizing the "highest risk." I anticipate
      that sophisticated interactive computer programs will be effective in improving
      screening and case finding, thus bringing many more suicidal persons into contact
      with primary care physicians and outpatient mental health services for the
      purpose of relieving psychological pain. Computer programs will be invaluable in
      improving training for both primary care providers and outpatient mental health
      workers. Improved communication networks will prove to be useful resources for
      maintaining continuity of care and consultation, which is important in long-term
      treatment. Other technical developments include simplifying and making explicit
      various treatment approaches, in both psychotherapy and drug therapy, so that
      research can proceed to clarify what type of treatment helps which type of
      suicidal patient.

PMID- 7631368
TI  - Suicide prevention in adolescents (age 12-18).
AB  - The epidemiology of adolescent suicide is summarized with particular emphasis on
      temporal trends by age and gender. "First-generation" prevention programs, as
      reviewed and critiqued by the Centers for Disease Control and Prevention, are
      then examined. In the absence of compelling empirically based behavioral outcome
      data, selective targeted "second-generation" prevention efforts are then
      described across the primary-secondary-tertiary continuum. These efforts are
      focused toward targets of individual predisposition, the social milieu, or
      proximal agents associated with high risk for suicidal behaviors. Finally, with
      an eye toward the future, current obstacles and unanswered questions are explored
      as they relate to opportunities and hopes for change in effecting reduced rates
      of these behaviors.

PMID- 7631369
TI  - Suicide prevention in young adults (age 18-30).
AB  - The rate of suicide in young adults has more than doubled since 1950. This paper
      presents some explanations for this rise and analyzes the diagnoses and
      population groups whose high rates of suicide contribute most of this increase.
      The factors leading to suicide are presented for each group, and preventative
      interventions are developed from the analyses. Groups that can be readily
      affected by suicide reduction measures are discussed, and methods for reducing
      their suicide rates are proposed.

PMID- 7631370
TI  - Suicide prevention in adults (age 30-65).
AB  - Relatively little is known about midlife suicides, compared to adolescent and
      elderly suicides. A life-span model of suicidal behaviors is suggested as a
      heuristic conceptual tool. General midlife tasks and crises, as outlined by
      Levinson and Erikson, are reviewed. However, more than routine midlife
      developmental problems occur in most suicides. Some of the possible distinctive
      traits of midlife suicides (versus younger and older suicides) include: loss of
      spouse, years of heavy drinking, reaching the age of high depression risk, and
      occupational problems (including unemployment, inability to work, and
      retirement). Midlife suicide rates tend to be highest among white males, although
      female suicide rates peak in midlife. The paper concludes with a review of
      assessment and treatment issues related to a half-dozen high-risk midlife suicide
      types.

PMID- 7631371
TI  - Suicide prevention in the elderly (age 65-99).
AB  - Suicide rates by age are highest among older adults. Subpopulations of elderly
      adults at high risk are identified, including White males, the target of a
      Healthy People 2000 Objective. Several specific programs are described and a
      range of measures to prevent suicide in late life are suggested. These measures
      include primary prevention steps related to education and information
      dissemination, and secondary prevention involving early identification and
      assessment of the depressed and suicidal as well as improved referral efforts.

PMID- 7631372
TI  - Assisted suicide, euthanasia, and suicide prevention: the implications of the
      Dutch experience.
AB  - What impact would legalization of assisted suicide and euthanasia have on our
      ability to treat suicidal patients and to prevent suicide? Information from a
      study of the Dutch experience illustrates how legal sanction promotes a culture
      that transforms suicide into assisted suicide and euthanasia and encourages
      patients and doctors to see choosing death as a preferred way of dealing with
      serious or terminal illness. The extension of the right to euthanasia to those
      who are not physically ill further complicates the problem. So too does the
      tendency of doctors in such a culture to begin to feel that they can make
      decisions about ending the life of competent terminally ill patients without
      consulting the patient. "Normalizing" suicide as a medical option lays the
      groundwork for a society that turns euthanasia into a "cure" for suicidal
      depression.

PMID- 7631373
TI  - Epidemiology of suicidal behavior.
AB  - This paper presents the epidemiology of suicide and discusses the known risk
      factors for suicide within a framework designed to encourage a systematic
      approach to theory testing and prevention. Mental and addictive disorders are the
      most powerful of the multiple risk factors for suicide in all age groups. Since
      risk factors for suicide rarely occur in isolation, prevention efforts are more
      likely to succeed if multiple risk factors are targeted.

PMID- 7631374
TI  - On the nature, magnitude, and causality of suicidal behaviors: an international
      perspective.
AB  - The central questions addressed in this paper are whether present generations of
      adolescents and adults worldwide are at greater risk of developing suicidal
      reactions than previous generations were and what the possible causal mechanisms
      involved are. On the basis of data from international and national data banks as
      well as an extensive review of the literature, it is concluded that a true
      increase in suicide mortality and morbidity has occurred over the larger part of
      this century among the White urban adolescent and young adult populations of
      North America and Europe, particularly among (young) males over the last three
      decades. Among the possible causal mechanisms identified are (1) the
      corresponding increase in the prevalence of depressive disorders; (2) the
      corresponding increase in the prevalence of substance (ab)use and substance abuse
      disorders, and a lowering of age of onset of (ab)use; (3) psychobiological
      changes, in particular the dramatic lowering of the age of puberty; (4) an
      increase in the number of social stressors with extensive consequences for youth;
      (5) changes in attitudes towards suicidal behaviors and the related increased
      availability of suicidal models.

PMID- 7631375
TI  - Gender and the primary prevention of suicide mortality.
AB  - Primary prevention aims at reducing the incidence of a disorder. The first step
      in primary prevention involves documenting the magnitude of the problem and
      identifying risk factors. Consistent with primary prevention practices, we review
      the national and international epidemiological data on suicide mortality and then
      discuss the implications these data hold for primary prevention. Our approach is
      novel because we systematically examine the suicide epidemiology data by gender
      and culture. Suicide mortality appears to be highest among individuals (e.g.,
      young adult married females in some Papua New Guinea regions; older adult,
      isolated, White males in the United States) for whom such behavior is culturally
      sanctioned. Thus, an important target for primary prevention may be local
      cultures of gender and suicide.

PMID- 7631376
TI  - The place of suicide prevention in the spectrum of intervention: definitions of
      critical terms and constructs.
AB  - The authors trace the evolution of prevention models and conceptual foundations
      for the prevention of disorders starting with the public health/medical model and
      concluding with the contemporary model recently proposed by the Institute of
      Medicine of the National Academy of Sciences. They compare and contrast the
      contributions of each model toward the theoretical reduction of suicide in the
      general population. Risk and protective factors as they relate to suicidal
      behaviors are identified. The paper explores conceptual frameworks used to
      understand population-level risk factors and moves toward a discussion of how to
      target individuals at risk for suicidal behaviors. First-order and second-order
      targets of change in prevention efforts are defined and examples provided.

PMID- 7631377
TI  - Suicide prevention from a public health perspective.
AB  - The public health approach to health problems provides a strong framework and
      rationale for developing and implementing suicide prevention programs. This
      approach consists of health-event surveillance to describe the problem,
      epidemiologic analysis to identify risk factors, the design and evaluation of
      interventions, and the implementation of prevention programs. The application of
      each of these components to suicide prevention is reviewed. Suggestions for
      improving surveillance include encouraging the use of appropriate coding,
      reviewing suicide statistics at the local level, collecting more etiologically
      useful information, and placing greater emphasis on analysis of morbidity data.
      For epidemiologic analysis, greater use could be made of observational studies,
      and uniform definitions and measures should be developed and adopted. Efforts to
      develop interventions must include evaluating both the process and the outcome.
      Finally, community suicide prevention programs should include more than one
      strategy and, where appropriate, should be strongly linked with the community's
      mental health resources. With adequate planning, coordination, and resources, and
      the public health approach can help reduce the emotional and economic costs
      imposed on society by suicide and suicidal behavior.

PMID- 7631378
TI  - Suicide prevention programs: issues of design, implementation, feasibility, and
      developmental appropriateness.
AB  - Emerging models of prevention focus on population-level risk reduction through
      enumerating antecedent conditions that are linked to subsequent expressions of
      disorder and dysfunction. The authors discuss the essential ingredients for
      successful prevention programs--comprehensiveness, fidelity, and intensity. The
      authors describe how to mount prevention programs to increase feasibility,
      access, and effectiveness. Suicide is an epidemic of low frequency in the general
      population and therefore does not receive appropriate attention in public health
      prevention campaigns. They argue for nesting suicide prevention programs within
      existing public health preventive intervention programs and provide some examples
      of how to reduce vulnerabilities and risk conditions for subsequent suicidal
      behaviors.

PMID- 7631379
TI  - [The response to Wilhelm Conrad Rontgen's discovery in Berlin].
AB  - In early January 1896 Wilhelm Conrad Rontgen sent offprints to several colleagues
      of his to make them acquainted with his discovery of the X-rays. From January 5,
      1896 newspapers started reporting on that discovery worldwide from Vienna. In
      several cities the news immediately set off corresponding scientific activities
      among specialists. This paper looks into such activities carried out in Berlin to
      show how promptly Rontgen's discovery was taken up, with a number of priorities
      having been set in the capital of the German Reich. The X-ray photographs which
      Rontgen had forwarded together with his offprints were displayed and discussed at
      a meeting of the Berlin Physical Society as early as on January 4, 1896, making
      his discovery known to the public for the first time. On January 6, 1896 the
      discovery and photographs were presented at a session of the Berlin Association
      of Internal Medicine and its diagnostic application was discussed in the medical
      community for the first time. A few days after that, the first photographs shot
      by other authors after Rontgen, and their diagnostic use, were demonstrated in
      Berlin. Finally, Rontgen's early visit to Emperor William II on January 12, 1896,
      which led to the speedy introduction of the X-day technique into German military
      medicine, is discussed in detail.

PMID- 7631380
TI  - [The fate of Karl Sudhoff's Paracelsus library].

PMID- 7631381
TI  - [Hospitals in Prague from the high Middle Ages to the Enlightenment (1135-1800)].
AB  - Based on hitherto unknown layouts and documents from the Prague archives, this
      paper reviews the evolution of the health care system in the capital of Bohemia.
      From the high Middle Ages to the Enlightenment, the town's history as well as
      changing political and religious tendencies provide a unique background for the
      development of different types of institutions for the care of the poor and sick.
      The first charitable foundations of the sovereigns and the archbishops were soon
      followed by the semi-monasterial infirmaries of the Hospitallers. Leprosoria and
      other shelters for the contagious deserve special attention. After the counter
      reformation, the newly built hospitals of orders like the Brothers of Saint John
      of God and the Sisters of Saint Elizabeth played an important role. From the
      architectural point of view, the baroque hospitals built by Kilian Ignaz
      Dientzenhofer belong to the most impressive examples of hospital architecture in
      Europe. Finally, the medical reforms of Emperor Joseph II. led to a series of
      completely new institutions, which can be regarded as the beginning of modern
      medicine im Bohemia. It was especially intended to describe exactly the site and
      the architectonic appearance of the preserved buildings. Thus, the medical
      historian can contribute to the care and preservation of these medical monuments.

PMID- 7631382
TI  - Will human immunodeficiency virus p24 antigen screening increase the safety of
      the blood supply and, if so, at what cost?

PMID- 7631383
TI  - The need for a national blood product monitoring system: role of hemophilia
      registries.

PMID- 7631384
TI  - How much would the safety of blood transfusion be improved by including p24
      antigen in the battery of tests?
AB  - BACKGROUND: Because p24 antigen may be detectable during seroconversion, before
      antibodies, some of the infected blood undetected by antibody screening could be
      identified through antigen screening. STUDY DESIGN AND METHODS: The potential
      benefit of antigen screening was evaluated in a simulation model incorporating
      present knowledge of the time sequence from antigen exposure to antibody
      development during seroconversion and the incidence of seroconversion among
      repeat donors. The model was designed so that the results were consistent with
      the observed rate of antibody-positive blood donations and the CIs of surveys
      that did not find any antibody-negative/antigen-positive donated blood. RESULTS:
      In the United States in 1990, the number of expected, undetected, contaminated
      blood components was estimated at 68; of these 8 to 17 could have been identified
      by antigen screening, depending on the hypothesis explored. (In 1992, 20
      undetected, contaminated blood components were expected according to this model,
      of which 2 to 5 could have been identified by antigen screening.) In France, the
      comparable figures were 1 to 4 of 13 in 1990 and 1 to 2 of 7 in 1992. CONCLUSION:
      The projected benefit must be weighted against possible negative consequences,
      including 1) an increase in recently infected persons seeking p24 antigen
      screening at blood banks (assuming this test is not incorporated into screening
      in non-blood bank settings) and 2) the need for additional quality assurance
      procedures to avoid operational flaws associated with the increase in the donor
      screening test battery. In any case, the best way of increasing the safety of
      blood is improvement in the selection of donors, which can diminish the residual
      risk of transmission of any viruses.

PMID- 7631385
TI  - The Canadian Hemophilia Registry as the basis for a national system for
      monitoring the use of factor concentrates.
AB  - BACKGROUND: Canada's publicly funded blood system has recently introduced high
      purity concentrates as the standard treatment for individuals with hemophilia.
      The added cost and the need to document patient outcomes have prompted the
      consideration of a national blood product monitoring system. STUDY DESIGN AND
      METHODS: This study investigates the suitability of the Canadian Hemophilia
      Registry (CHR) as the basis of such a monitoring system by assessing the degree
      to which it represents users of factor concentrates. RESULTS: Currently, there
      are 1978 individuals registered with the CHR, of whom 1594 (81%) have hemophilia
      A and 384 (19%) have hemophilia B. The total prevalence is 7.2 per 10(5)
      population, with the prevalence of severe cases being 2.3 per 10(5). This overall
      prevalence is similar to that seen in other countries with national registries.
      The CHR national prevalence also compares favorably with that in the province of
      Quebec, where registration of users of blood products is compulsory. The CHR
      figures indicate that the number of persons currently infected with human
      immunodeficiency virus, both alive and dead, is 652, which is similar to the
      number of applicants (658) to the federal government's assistance program. The
      registry is stable, and the number of persons with severe cases, other than young
      children, newly registered or lost to follow-up during the last 2 years is very
      small. CONCLUSION: The CHR includes the vast majority of factor concentrate users
      and is therefore ideal as the basis for a national monitoring system.

PMID- 7631386
TI  - Comparison of the efficacy of blood and polyethylene glycol-hemoglobin in
      recovery of newborn piglets from hemorrhagic hypotension: effect on blood
      pressure, cortical oxygen, and extracellular dopamine in the brain.
AB  - BACKGROUND: Successful blood substitutes, when infused in place of an equal
      volume of whole blood, provide similar delivery of oxygen to the tissues without
      introducing abnormalities in cellular metabolism. STUDY DESIGN AND METHODS: Equal
      volumes of whole blood (control), polyethylene glycol-hemoglobin solution at 6 g
      per dL, dextran solution, and physiologic saline were compared for their ability
      to reverse the effects of hemorrhagic hypotension on oxygenation and dopamine
      metabolism in the brain of newborn piglets. The decrease in mean arterial blood
      pressure was used as a measure of the hemorrhagic insult. Cerebral oxygen
      pressure was determined optically by the oxygen-dependent quenching of
      phosphorescence, and the extracellular level of dopamine in the corpus striatum
      was determined by in vivo microdialysis. RESULTS: Following a 2-hour
      stabilization after implantation of the microdialysis probe in the corpus
      striatum, the mean arterial blood pressure was decreased from 88 +/- 7 torr
      (control) to 42 +/- 5 torr by the removal of blood in a stepwise manner, over a
      period of 60 minutes. Decrease in mean arterial blood pressure caused a
      progressive stepwise decrease in cortical oxygen pressure from 48 +/- 5 torr to
      16 +/- 4 torr at the end of bleeding. As a consequence of the decrease in oxygen
      pressure, extracellular dopamine increased progressively to about 2300 percent of
      the control value. When a volume of blood equal to that removed was returned and
      bicarbonate was injected to help correct arterial pH, blood pressure, cortical
      oxygen pressure, and extracellular dopamine all returned within the 20- to 30
      minute recovery period to values not significantly different from control values.
      An equal volume of polyethylene glycol-hemoglobin solution, even with
      significantly lower hemoglobin content than whole blood, gave results comparable
      to those with whole blood. CONCLUSION: Polyethylene glycol-hemoglobin solution,
      like whole blood but in contrast to physiologic saline or dextran solution, was
      capable of returning the mean arterial blood pressure, cortical oxygen pressures,
      and extracellular dopamine nearly to control levels after acute blood loss in
      newborn piglets.

PMID- 7631387
TI  - Acute normovolemic hemodilution is a cost-effective alternative to preoperative
      autologous blood donation by patients undergoing radical retropubic
      prostatectomy.
AB  - BACKGROUND: Preoperative autologous blood donation is accepted as a standard of
      care for radical prostatectomy. Acute normovolemic hemodilution (ANH) is an
      alternative method for obtaining autologous blood. The cost and benefits of these
      two autologous blood-collection techniques are compared. STUDY DESIGN AND
      METHODS: Thirty consecutive patients scheduled for radical prostatectomy
      underwent ANH to a target hematocrit level of 28 percent. Blood was transfused in
      the perioperative period to maintain the hematocrit level > 25 percent.
      Hematocrit levels, transfusion outcomes and costs, and postoperative outcomes for
      these patients (hemodilution group) were compared with a matched patient cohort
      who preoperatively donated 3 units of blood for autologous use in prostatectomy
      surgery (nonhemodilution group, n = 30). RESULTS: Thirty patients underwent ANH
      to a hematocrit level of 28.7 +/- 1.7 percent, and 1740 +/- 346 mL (3.5 +/- 0.7
      units) of blood were collected. Three (10%) of the patients in each cohort had
      allogeneic blood exposure. Transfusion costs were 73 percent higher for the
      nonhemodilution group patients than for the hemodilution group patients ($330 +/-
      $100 vs. $191 +/- $55, p < 0.001). No differences were found in postoperative
      outcomes. CONCLUSION: An integrated blood conservation program utilizing
      hemodilution and a defined transfusion trigger can decrease the requirement for
      preoperative donation of blood for autologous use in radical prostatectomy. Point
      of-care autologous blood procurement is more cost-effective than preadmission
      donation of autologous blood units.

PMID- 7631388
TI  - Evidence that CDw108 membrane protein bears the JMH blood group antigen.
AB  - BACKGROUND: CDw108 is a cluster-of-differentiation antigen that resides on a
      glycosylphosphatidylinositol (GPI)-linked protein; it has not previously been
      shown to be expressed on red cells. JMH is a high-frequency red cell blood group
      antigen that resides on a GPI-linked protein of molecular weight similar to that
      bearing CDw108. The purpose of this study was to investigate whether CDw108 is
      expressed on red cells and whether it resides on the same membrane protein as
      does JMH. STUDY DESIGN AND METHODS: Murine monoclonal antibodies to CDw108, MEM
      121 and MEM-150, as well as a murine monoclonal antibody and human antibodies to
      JMH were used in radioimmunoassay, inhibition assay, Western blotting, and
      monoclonal antibody-specific immobilization of erythrocyte antigen assay.
      RESULTS: MEM-121 and MEM-150 were found to bind to red cells, and MEM-150 blocked
      binding of human anti-JMH to red cells. Anti-CDw108 and anti-JMH identified red
      cell membrane proteins that were of similar size and that were absent from JMH
      negative red cells on Western blotting. MEM-150 and MEM-121 also immobilized the
      same protein that reacted with human anti-JMH. CONCLUSION: CDw108 is expressed on
      red cells and resides on the same GPI-linked membrane protein as does the JMH
      blood group antigen.

PMID- 7631389
TI  - Identification of variant glycophorins of human red cells by lectinoblotting:
      application to the Mi.III variant that is relatively frequent in the Taiwanese
      population.
AB  - BACKGROUND: Detection of normal and variant glycophorin electrophoretic bands
      with T- and Tn-specific lectins is based on the possibility of glycophorin
      transformation into T or Tn antigens by simple chemical modifications in the
      blot. STUDY DESIGN AND METHODS: Human red cell membrane proteins were
      fractionated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and
      blotted onto nitrocellulose. The blots were submitted to mild acid hydrolysis
      (desialylation of glycophorins exposing T antigens) and then to Smith degradation
      (degalactosylation of asialo-glycophorins exposing Tn antigens). The modified
      glycophorin bands were detected with biotinylated lectins and horseradish
      peroxidase-conjugated avidin. RESULTS: The lectins from Artocarpus integrifolia
      (jacalin, anti-T/Tn), Amaranthus hybridus (anti-T), Salvia sclarea (anti-Tn), and
      Vicia villosa (anti-Tn) were used. The lectins detected normal glycophorin bands
      in control and variant red cells and characteristic additional bands in Mi.III
      (GP.Mur) red cells. The sensitivity of the method is comparable to that obtained
      by immunoblotting with glycophorin monoclonal antibodies. Comparison of the
      electrophoretic mobility of normal and variant bands is helpful in the
      classification of glycophorin variants. CONCLUSION: Lectinoblotting, based on
      carbohydrate recognition, enables the detection in a red cell sample, with high
      sensitivity, of all normal and variant glycophorin bands. The method can be also
      applied to other purposes, such as the identification of poly-O-glycosylated
      glycoproteins in other cells or the characterization of glycosylation of
      glycophorins and other poly-O-glycosylated proteins.

PMID- 7631391
TI  - Multiple or uncommon red cell alloantibodies in women: association with
      autoimmune disease.
AB  - BACKGROUND: Patients with multiple or uncommon red cell (RBC) alloantibodies
      require special efforts in the blood bank. This study investigated whether such
      persons had other immune-related conditions that might help to explain or predict
      their propensity for RBC antibody formation. STUDY DESIGN AND METHODS: Charts
      were retrospectively reviewed of 29 men and 83 women with multiple (> or = 3) RBC
      antibodies of potential clinical significance, uncommon RBC antibodies (anti-e, 
      Kpb, -Jkb, -Fyb, -S, -U, -Yta, -Dib, -Ata), or both. The clinical features in 43
      women with multiple antibodies were compared to those in two equal-sized control
      cohorts of women matched for transfusion-related diagnoses, but having either one
      RBC antibody or none. RESULTS: Women with uncommon RBC antibodies had a 33
      percent (18/54) prevalence of autoimmune disease. Twenty-eight percent of the 43
      women with multiple antibodies had autoimmune disease, compared to 14 percent of
      women in the cohort with one RBC antibody (p = 0.09) and 7 percent of those in
      the cohort without RBC antibodies (p = 0.01). Only one of the 29 men had
      autoimmune disease. CONCLUSION: Autoimmune disease is a common underlying factor
      in women who make multiple or uncommon RBC alloantibodies of potential clinical
      significance.

PMID- 7631390
TI  - Le(a) and Le(b) tissue glycosphingolipids.
AB  - BACKGROUND: The Le(a) and Le(b) antigens are synthesized by cells making exocrine
      secretions, but it is not well-defined where plasma and red cell Le(a) and Le(b)
      antigens are made. STUDY DESIGN AND METHODS: This study uses chromatographic and
      immunochemical methods to extract Le(a) and Le(b) glycolipids from human tissues.
      RESULTS: Le(a) and Le(b) antigens may be synthesized by both epithelial and
      mesodermal tissues. Expression of Lewis transferase activity was demonstrated in
      various tissues, confirming the epistatic interaction by Le and H genes to form
      the Leb antigen. CONCLUSION: The Le(a) and Le(b) substances found in plasma might
      originate from the epithelial cells of the digestive tract.

PMID- 7631392
TI  - Comparison of hematopoietic progenitor cells in human umbilical cord blood
      collected from neonatal infants who are small and appropriate for gestational
      age.
AB  - BACKGROUND: Cord blood has been used for transplantation. The purpose of this
      study was to compare numbers of hematopoietic progenitors in cord blood collected
      from neonatal infants who are small for their gestational age and those who are
      normal. STUDY DESIGN AND METHODS: Sixteen pregnant women diagnosed with
      intrauterine growth restriction were prospectively identified. Cord blood was
      collected at delivery. Fourteen cord blood samples were obtained from gestational
      age-matched, appropriately grown newborns. In vitro assays for hematopoietic
      progenitors were performed and results of the two compared. Comparisons were also
      made with numbers of hematopoietic progenitor cells previously found by this
      laboratory in samples collected with the possibility of use for transplantation.
      RESULTS: Gestational age, the women's pregnancy and delivery histories, maternal
      risk factors for intrauterine growth restriction, maternal age, delivery method,
      umbilical cord blood gases, and 5-minute Apgar scores were similar in the two
      groups. Newborns who were small for their gestational age had significantly lower
      birth weights and longer stays in the neonatal intensive care unit with no
      evidence for viral infections in the immediate neonatal period. The mean number
      of progenitors per collection of cord blood in the small newborns was about half
      that per collection from appropriately grown newborns, but in most cases, these
      differences were not significant in the two groups, and many numbers in the small
      newborns fell within the range associated with successfully engrafting cord blood
      collections. CONCLUSION: Hematopoietic progenitor cells in the small newborns may
      be adequate for transplantation purposes in many cases. Their possible use in
      this context should, however, involve careful consideration of the numbers of
      progenitors collected as well as of possible viral or other contamination.

PMID- 7631393
TI  - Transfusion of donor-type red cells as a single preparative treatment for bone
      marrow transplants with major ABO incompatibility.
AB  - BACKGROUND: Major ABO incompatibility of a bone marrow donor and recipient
      entails the risk of severe hemolytic transfusion reactions. STUDY DESIGN AND
      METHODS: Nineteen patients who received transplants of bone marrow from donors
      whose ABO type was a major mismatch with the recipients were treated with plasma
      exchanges transfusion (n = 7) or donor-type red cell transfusion (n = 12) to
      remove isoagglutinins from the recipient. Efficacy, side effects, engraftment,
      and transfusion requirements were analyzed for the two treatment groups. RESULTS:
      Both treatment methods were well tolerated, were of comparable efficacy in
      removing ABO antibodies, and did not affect the engraftment of platelets, red
      cells, or white cells. Except for observations in one patient, whose renal
      function was already impaired before red cell treatment and who developed
      reversible renal failure after transplant, no significant differences in serum
      creatinine levels were observed in the two groups after treatment. Only serum
      levels of lactate dehydrogenase measured, as a sign of hemolysis, on Day 0 (488
      +/- 110 vs. 191 +/- 30 U/L in the red cell and plasma exchange groups,
      respectively, p < 0.05) were higher in the red cell group than in the plasma
      exchange group. CONCLUSION: Transfusion of donor-type red cells is an effective
      means of preventing hemolytic reactions in patients who receive marrow
      transplants from donors whose ABO type is a major mismatch. It is technically
      simple and well tolerated, even in patients with high-titer isoagglutinins, but
      it should be avoided in patients with abnormal renal function.

PMID- 7631395
TI  - Comparison of two anti-hepatitis C virus enzyme-linked immunosorbent assays.
AB  - BACKGROUND: Third-generation anti-hepatitis C virus (HCV) enzyme-linked
      immunosorbent assays (ELISA) are now implemented in most laboratories in Europe,
      but have not yet been fully implemented in the United States. STUDY DESIGN AND
      METHODS: Two ELISAs (Ortho 3.0 and Ortho 2.0, Ortho Diagnostics, Raritan, NJ)
      were compared by tests on various serum panels: A) blood donor samples (n = 530)
      that tested positive in first- or second-generation anti-HCV ELISA; B) samples
      from persons with chronic non-A, non-B hepatitis (n = 185); C) samples from
      multiply transfused patients (n = 79); D) samples from patients on hemodialysis
      (n = 473); and E) samples from Dutch random blood donors (n = 2153). RESULTS: In
      panels A, B, and C, 247 (100%) of 247 polymerase chain reaction (PCR)-positive
      and 278 (100%) of 278 second-generation recombinant immunoblot assay (RIBA-2)
      positive specimens were detected by Ortho 2.0 and 3.0 (sensitivity, 100%). In the
      sera of panel D, used to represent a group of patients with a high risk for HCV,
      no additional positives were found by Ortho 3.0. In panel E, of 2153 blood donor
      samples, 2 (0.1%) were positive in Ortho 2.0 and 8 (0.4%) in Ortho 3.0. Two
      samples that were positive in both Ortho 2.0 and 3.0 were also positive in RIBA
      2; one was positive on PCR. From the 6 remaining Ortho 3.0-positive (Ortho 2.0
      negative) samples, 1 was positive in RIBA-2 (isolated anti-c100) and 3 were
      positive in third-generation RIBA (1/3 isolated anti-c100, 2/3 isolated NS5). All
      6 samples were PCR negative. In first-time donors, no difference in specificity
      was found. CONCLUSION: The sensitivity and specificity of the Ortho 3.0 ELISA are
      comparable to those of the Ortho 2.0 ELISA.

PMID- 7631394
TI  - Contribution of polymerase chain reaction and radioimmunoprecipitation assay in
      the confirmation of human T-lymphotropic virus infection in French blood donors.
      Retrovirus Study Group of the French Society of Blood Transfusion.
AB  - BACKGROUND: To verify the criteria for human T-lymphotropic virus (HTLV)
      seropositivity in Western blot (WB) proposed by the Retrovirus Study Group of the
      French Society of Blood Transfusion, 186 blood donations that were repeatedly
      reactive in HTLV enzyme-linked immunosorbent assay, selected according to their
      WB pattern, were tested by polymerase chain reaction (PCR) and
      radioimmunoprecipitation assay (RIPA). STUDY DESIGN AND METHODS: In two
      commercially available WBs, 12 samples were confirmed as positive (rgp21+p19+p24)
      and 174 were interpreted as indeterminate (one or two reactivities to these
      proteins). The primer pairs used for the PCR allowed the amplification of type I
      (HTLV-I) or type II (HTLV-II) (or both) sequences. The RIPA was performed with
      two 35S-labeled cell lines: HTLV-I infected HUT 102/B2 and HTLV-II-infected MoT.
      RESULTS: Of the 12 positive samples, 11 were classified as HTLV-I-positive and
      one as HTLV-II-positive. Among the 174 indeterminate samples, three (WB pattern:
      rgp21+, p19+, p24-) were HTLV-I positive in PCR (one of them was positive in RIPA
      also); the other 171 were HTLV negative. CONCLUSION: In the study of a population
      in which 97 percent of HTLV infections are due to HTLV-I, these data support the
      three-protein criteria (rgp21, p19, and p24) for a positive blot reading. No HTLV
      infection was observed when rgp21 did not react. Consequently, p19 and/or p24
      band patterns represent false reactivity and do not require PCR or RIPA
      confirmation. To discriminate between false- and true-positive results in the
      absence of MTA-1 or K55 reactivity, PCR and/or RIPA is required only when rgp21
      reactivity is associated with one gag band (p19 or p24).

PMID- 7631396
TI  - Transfusion practices in human immunodeficiency virus-infected patients.
AB  - BACKGROUND: The reported immunomodulatory effects of transfusion raise concern
      about the potential for virus activation and tumor growth in human
      immunodeficiency virus (HIV)-infected patients. In the absence of "standards" of
      transfusion practice for such patients, a survey of transfusion policies among
      institutions specializing in the care of HIV-infected patients was performed to
      delineate current practices. STUDY DESIGN AND METHODS: A survey developed by the
      Transfusion Practices Committee of the American Association of Blood Banks was
      sent to 47 AIDS clinical trial units and 14 regional hemophilia centers in North
      America. RESULTS: Forty-three percent of centers completed the survey. Most
      centers observed more than 200 HIV-infected patients each. The key findings were
      that 1) 81 percent of centers used identical red cell transfusion criteria for
      HIV-infected and noninfected patients; 2) 52 percent used recombinant human
      erythropoietin as initial treatment for zidovudine-induced anemia, while 46
      percent used recombinant human erythropoietin for anemia not associated with
      zidovudine; 3) 35 percent of centers used white cell-reduced blood components in
      lieu of cytomegalovirus (CMV)-seronegative components when administering
      transfusion(s) to CMV-seronegative patients; 4) 27 percent gamma-radiated
      cellular components, but no case of graft-versus-host disease had been observed;
      5) > 85 percent of centers used monoclonal factor VIII for pediatric and adult
      hemophiliacs infected with HIV; 6) approximately one-third of centers routinely
      white cell-reduced cellular components; and 7) the most common reasons for white
      cell reduction included reduction of febrile reactions and CMV risk, reduction of
      platelet alloimmunization, and delay of immunomodulatory consequences of
      transfusion. CONCLUSION: There is marked heterogeneity in transfusion practice
      for HIV-infected patients. Modification of cellular components to achieve
      different objectives is routine in many centers.

PMID- 7631397
TI  - The first use of a centrifuge to detect red cell agglutination.

PMID- 7631398
TI  - Umbilical cord blood transplantation.
AB  - Interest in umbilical cord blood as an alternative source of hematopoietic stem
      cells is growing rapidly. Umbilical cord blood offers the clinician a source of
      hematopoietic stem cells that are readily available and rarely contaminated by
      latent viruses. Moreover, the collection of umbilical cord blood poses no risk to
      the donor; there is no need for general anesthesia or blood replacement, and the
      procedure causes no discomfort. Whether cord blood lymphocytes are as likely to
      cause GVHD as lymphocytes from older individuals is unknown. Current clinical
      experience would suggest that the incidence may be low. Few of the patients who
      have thus far received umbilical cord blood, including recipients of HLA
      disparate grafts, have developed clinically significant GVHD. These results and
      associated laboratory findings pose intriguing possibilities for the future of
      umbilical cord blood stem cells in the setting of unrelated-donor
      transplantation. With the marked incidence of Grade 2 to 4 acute GVHD that is
      currently observed after unrelated-donor bone marrow transplantation, a reduction
      in incidence or severity would be a major advance in this field. In the setting
      of autologous marrow transplantation, there are other intriguing possibilities;
      for example, cord blood may be an optimal source of pluripotential stem cells for
      use in gene therapy. As detailed in Broxmeyer's review, the large-scale
      collection and storage of cord blood stem cells is no longer just a concept; it
      has become a reality. Pilot programs for the banking of unrelated-donor umbilical
      cord blood have already begun in the United States and Europe.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7631399
TI  - Neutrophil alloantigens at the molecular level.

PMID- 7631400
TI  - Cost of compliance: is politics involved?

PMID- 7631401
TI  - Efficacy of autologous fresh whole blood or platelet-rich plasma in adult cardiac
      surgery.
AB  - BACKGROUND: Transfusing fresh autologous blood during cardiac surgery may improve
      hemostasis and decrease the need for transfusion. STUDY DESIGN AND METHODS: A
      prospective randomized study was performed with fresh whole blood (WB) obtained
      by intraoperative hemodilution (IH) and with platelet-rich plasma (PRP) obtained
      by perioperative apheresis from adult cardiac surgery patients. RESULTS: Seventy
      patients were randomly assigned to three arms: 24 to the PRP arm, 18 to the IH
      arm, and 28 to serve as controls. A mean of 924 +/- 130 mL of WB was collected
      from the IH group, and a mean of 650 +/- 124 mL of PRP was collected from the PRP
      group (mean, 1.42 +/- 0.74 x 10(11) platelets); these components were transfused
      after bypass. Preoperative measures were similar among groups. Intraoperatively,
      the groups did not differ in bypass time, estimated blood loss, number of
      transfusions, or proportion receiving transfusion(s). Postoperatively, control
      patients had more mediastinal drainage (736 mL vs. 476 mL [IH] and 463 mL [PRP];
      p = 0.014), but there was no difference in the proportion of patients requiring
      red cell transfusion (p = 0.87), the hemoglobin at discharge (p = 0.20), or the
      length of hospitalization (p = 0.57). CONCLUSION: Although a hemostatic benefit
      manifested as reduced postoperative bleeding was observed, this study does not
      support the use of fresh blood components obtained by IH or PRP collection during
      low-risk cardiac surgery. Additional studies are needed to assess whether more
      aggressive component collection or the use of these techniques in high-risk cases
      may have a greater impact on clinical outcome variables, including transfusion.

PMID- 7631402
TI  - Anti-A and/or anti-B is not detectable in some patients who underwent ABO
      incompatible bone marrow transplantation.
AB  - BACKGROUND: Recently, anti-A and/or anti-B produced by B cells from donor marrow
      could not be detected for more than 20 weeks in some patients who had undergone
      ABO-incompatible bone marrow transplantation (BMT). STUDY DESIGN AND METHODS:
      Twelve to 72 weeks after 11 patients underwent ABO-incompatible BMT, titers of
      anti-A and anti-B were assayed, A and B antigens were identified by routine
      methods and flow cytometry, direct and indirect antiglobulin tests were
      performed, and the red cell antibody was eluted. RESULTS: In some patients who
      underwent ABO-incompatible BMT, anti-A and/or anti-B produced by the B cells from
      the donor marrow could not be detected after BMT when red cells taken from the
      patients before BMT carried the corresponding antigen--that is, when
      hematopoiesis had already changed the cells to the donor's type according to ABO
      blood typing. Furthermore, some blood samples from those patients gave positive
      results in direct antiglobulin tests. Blood typing of patients after BMT showed
      mixed-field agglutination. In one patient, the half-life of red cells assayed
      with 51Cr was 22.4 days (30.0 +/- 4.0 days for normal controls). CONCLUSION:
      Although many hypotheses could be considered to explain the present data, the
      possibility is proposed that anti-A and/or anti-B in the sera must have been
      consumed in some patients who underwent ABO-incompatible BMT. This may lead to
      problems such as difficulty of ABO typing, positive direct antiglobulin tests,
      and a relatively short life span of red cells.

PMID- 7631403
TI  - Preoperative autologous blood donation: benefit or detriment? A mathematical
      analysis.
AB  - BACKGROUND: Advocates of preoperative autologous blood donation (PABD) often fail
      to consider the needs of individual patients and the effects of donation on
      hematocrit. Mathematical modeling is used here to analyze PABD. STUDY DESIGN AND
      METHODS: A model of PABD was constructed to simulate the transfusion of red cells
      once a predetermined minimum hematocrit was reached. Preoperatively deposited
      units not needed to maintain a hematocrit at this level were not transfused.
      Final hematocrits were compared to the hematocrit that would be expected if the
      patient had not donated blood for his or her own operative use. RESULTS: For many
      patients, particularly those with normal initial hematocrits, large estimated
      blood losses must occur before the minimum hematocrit is reached. It is also
      known that patients donating multiple units typically cannot maintain their
      baseline hematocrit. In such cases, for blood losses of any volume, the final
      hematocrit was lower if units were collected preoperatively and transfusion did
      not occur. Preoperatively donating patients are more likely to be transfused
      earlier and more frequently than nondonating patients. Derived figures, based on
      individual patient values, help predict which patients will benefit most from
      PABD. CONCLUSION: PABD may actually lead to decreased postoperative hematocritis
      (with enhanced risk of ischemia) and otherwise unnecessary transfusions.

PMID- 7631405
TI  - Red cell surface cysteine residue (285) of D polypeptide is not essential for D
      antigenicity.
AB  - BACKGROUND: Only one surface cysteine residue (285) has been thought to be
      involved in D antigenicity, according to studies using lyophilized or
      nonlyophilized red cell membranes. However, it has been reported that a 17-kDa
      chymotryptic fragment containing the N-terminus but not this cysteine residue is
      associated with D antigenicity. STUDY DESIGN AND METHODS: The role of the
      sulfhydryl (SH) group in D, c, and E antigenicity is assessed by using intact red
      cells treated with the reagents N-ethylmaleimide, 5,5'-dithiobis(2-nitrobenzoic
      acid), and 2-(4'-maleimidylanilino)- naphthalene-6-sulfonic acid. Antigenicity
      was appraised by hemagglutination titers and immunoprecipitation using human anti
      D, -c, and -E. RESULTS: Treatment with N-ethylmaleimide or 5,5'-dithiobis(2
      nitrobenzoic acid) at various concentrations (< or = 5 mM) or for various times
      (< or = 120 min) did not cause significant decrease in hemagglutination titers as
      compared to untreated intact red cells. Moreover, immunoprecipitation of Rh
      antigen-carrying peptides by human anti-D was not affected by prior treatment
      with N-ethylmaleimide or 2-(4'maleimidylanilino)-naphthalene-6-sulfonic acid.
      Efficacy of blockage of SH groups was demonstrated by inhibition of palmitic acid
      uptake by the Rh polypeptides for prior treatment with N-ethylmaleimide and by
      the presence of fluorescent Rh polypeptides for prior treatment with 2
      (4'maleimidylanilino)-naphthalene-6-sulfonic acid. CONCLUSION: SH group
      involvement is not essential for D, c, or E antigenic expression in intact red
      cells.

PMID- 7631404
TI  - Platelet refractoriness and alloimmunization in pediatric oncology and bone
      marrow transplant patients.
AB  - BACKGROUND: The purposes of this study were to determine the overall incidence of
      platelet refractoriness and alloimmunization among multiply transfused children
      on a medical oncology and bone marrow transplant service and to evaluate the
      effect of routine white cell reduction in blood components on that incidence.
      STUDY DESIGN AND METHODS: The platelet transfusion records of 128 consecutive
      children admitted to the hospital and requiring blood component support for the
      treatment of disease were evaluated retrospectively. Mean corrected count
      increments (CCIs) for each patient were calculated for all random-donor platelet
      transfusions given within 7 days of the routine weekly testings of the patient's
      serum for lymphocytotoxic antibodies (LCTAbs). Mean CCIs for HLA-matched platelet
      transfusions were calculated separately for the patients receiving them. RESULTS:
      Thirty-one patients (24%) had or developed persistently positive LCTAbs
      (patient's serum reacted with > or = 3/10 panel lymphocytes); 22 (71%) of these
      patients had a mean CCI < 7.5 to random-donor platelet transfusions. In contrast,
      of the 97 patients with negative or transiently positive LCTAbs, only 25 (26%)
      had a mean CCI < 7.5. The overall incidence of platelet refractoriness (CCI <
      7.5) was 37 percent. Patients with acute myelogenous leukemia had a significantly
      (p < 0.01) reduced incidence (17%) of low CCIs, with or without positive LCTAbs,
      as compared to patients with other malignant or nonmalignant disorders (41%). No
      difference in the incidence of LCTAbs or low CCIs was seen in patients undergoing
      allogeneic or autologous bone marrow transplant or receiving drug therapy only.
      Among the 24 patients who received HLA-matched platelets, only those with
      positive LCTAbs showed a significant improvement in CCIs over that achieved with
      random-donor platelet transfusions. Routine white cell reduction in red cell and
      platelet components with third-generation white cell filters was performed prior
      to transfusion in 73 of the patients. There was no significant difference between
      the incidence of LCTAbs and/or low CCIs in this group and that in the 55 children
      receiving unfiltered transfusions. CONCLUSION: Alloimmunization and platelet
      refractoriness occur in pediatric oncology and bone marrow transplant patients,
      but the incidence--particularly in children with acute myelogenous leukemia-
      appears to be low. The detection of LCTAbs predicts a poor response to random
      donor platelet transfusion, but most such patients show improved CCIs with HLA
      matched platelets. Routine use of white cell-reduction filters has thus far
      failed to eliminate alloimmunization in children requiring prolonged blood
      component support.

PMID- 7631406
TI  - Platelet concentrates promote procoagulant activity: evidence from experimental
      studies using a perfusion technique.
AB  - BACKGROUND: Evaluation of the hemostatic effectiveness of platelet transfusions
      is difficult. Perfusion methods have been employed to test the quality and
      function of platelet concentrates, allowing differentiation between platelet
      platelet and platelet-surface interactions. STUDY DESIGN AND METHODS: A study was
      performed to investigate platelet adhesive and cohesive properties as well as the
      formation of fibrin when aliquots of platelet concentrates were added to
      thrombocytopenic blood. Blood previously anticoagulated with low-molecular-weight
      heparin (20 U/mL) underwent platelet and white cell reduction by filtration.
      Perfusates were prepared by adding to filtered blood platelets obtained from
      standard concentrates (stored for 1, 3, and 5 days). The final platelet count in
      these perfusates was standardized at 80,000 per microL. After perfusions,
      platelet-subendothelium interaction and fibrin formation were analyzed
      morphometrically. Results were always compared with those obtained in unfiltered
      blood (> 150,000 platelets/microL). RESULTS: A slight impairment in the ability
      of stored platelets to interact with the subendothelium was noticed during the
      storage period. However, the presence of fibrin was significantly greater than
      that observed in studies with unfiltered blood (Day 1 = 23.48 +/- 9.43%*; Day 3 =
      26.99 +/- 6.74%*; Day 5 = 17.95 +/- 9.06% vs. unfiltered blood = 12.60 +/- 3.08%;
      *p < 0.05). The lower platelet counts (80,000/microL) in the perfusates
      containing platelets from concentrates could account for the reduced platelet
      subendothelium interactions, but they cannot explain the increments in fibrin
      formation. CONCLUSION: While the preparation and storage of platelets have a
      detrimental effect on platelet adhesiveness, such procedures can positively
      influence the platelet procoagulant activity necessary to platelet hemostasis.

PMID- 7631407
TI  - Allogeneic transplantation combining mobilized blood and bone marrow in patients
      with refractory hematologic malignancies.
AB  - BACKGROUND: Mobilized blood stem cells have been used successfully in autologous
      transplant recipients to reduce the complications of pancytopenia due to dose
      intensive chemotherapy. Reports of cytokine-mobilized blood progenitor cells in
      allogeneic transplant recipients are rare. STUDY DESIGN AND METHODS: This is a
      pilot trial of six patients. Patients with advanced hematologic malignancy
      received bone marrow (median total 2.6 x 10(8) mononuclear cells/kg) followed by
      four daily transfusions of blood (median total 9.5 x 10(8) mononuclear cells/kg)
      from HLA-matched sibling donors who were mobilized with recombinant human
      granulocyte-colony-stimulating factor (5 micrograms/kg/day subcutaneously for 5
      days). All patients received cyclosporine and prednisone for graft-versus-host
      disease (GVHD) prophylaxis. RESULTS: An absolute neutrophil count greater than
      500 per mm3 was achieved on Day 12, and platelet transfusion independence was
      achieved on Day 16. The median day of hospital discharge was Day 23 after
      transplant. All patients achieved 100-percent donor cell engraftment. Acute > or
      = Grade III GVHD did not develop in any patients, but all patients developed
      Grade I (n = 4) or Grade II (n = 2) acute GVHD. Chronic extensive GVHD developed
      in four of six patients. One patient died of pneumonia 263 days after transplant
      while undergoing immune-suppressive therapy for chronic GVHD. CONCLUSION: The
      transfusion of blood stem cells in patients undergoing allogeneic bone marrow
      transplant is well tolerated soon after transplant, but the development of
      chronic GVHD may limit the general usage of unmanipulated blood stem cells.

PMID- 7631408
TI  - Patterns of care for and outcomes of Pneumocystis carinii pneumonia among persons
      with transfusion-acquired AIDS.
AB  - BACKGROUND: The most common human immunodeficiency virus (HIV)-related cause of
      death in persons with transfusion-acquired (TA) AIDS has been Pneumocystis
      carinii pneumonia (PCP). While better treatment for PCP accounts for improved
      survival among HIV-infected homosexual or bisexual men, the extent to which
      others have benefitted from these developments is unknown. STUDY DESIGN AND
      METHODS: Patterns of PCP care among persons with TA-AIDS, intravenous drug users,
      and homosexual or bisexual men are compared. RESULTS: TA-AIDS patients were older
      (mean, 46 years vs. < 40 for others, p < 0.05), more severely ill (59% had an
      alveolar-arterial oxygen gradient > 48.5 torr vs. 41% of others, p < 0.05), and
      less likely to have received PCP prophylaxis (16% of TA-AIDS patients versus 24
      41% of others, p < 0.05). PCP care and outcomes also differed: TA-AIDS patients
      were less than half as likely to have early use of PCP medications (relative odds
      ratio = 0.45; 95% CI, 70% vs. > 80% for others, p < 0.05), more likely to be
      intubated (22% vs. 9-13% of others, p < 0.05), and more likely to die in-hospital
      (26% vs. 13-22% of others, p < 0.05). After controlling for differences in
      severity of illness, insurance, age, and hospital characteristics, TA-AIDS
      patients were 45 percent as likely to have early PCP therapy (95% CI, 22%, 91%)
      as were persons in high-risk groups. CONCLUSION: For persons whose only risk
      factor was transfusion, recognition of the HIV infection and its complications
      appears to be problematic, which may help explain poorer outcomes in persons with
      HIV-related PCP.

PMID- 7631409
TI  - Staff costs associated with the implementation of a comprehensive compliance
      program in a community blood center.

PMID- 7631410
TI  - Isoimmune neonatal neutropenia caused by Fc gamma RIIIb antibodies in a Spanish
      child.
AB  - BACKGROUND: Fc gamma RIIIb deficiency is a rare defect in which neutrophils do
      not express Fc gamma RIIIb and therefore the individuals with this defect have an
      NA null phenotype. Soluble Fc gamma RIII in plasma is severely decreased and
      almost undetectable. During pregnancy, Fc gamma RIIIb deficiency may cause the
      formation of maternal Fc gamma RIIIb antibodies, which leads to an isoimmune
      neonatal neutropenia. The first known case of isoimmune neonatal neutropenia
      caused by these antibodies in a Spanish child was identified. CASE REPORT: A
      newborn infant was severely affected by omphalitis; analysis of his blood showed
      an absolute neutropenia, but he responded well on intravenous immunoglobulin
      therapy. The maternal antiserum reacted strongly with all tested Fc gamma RIIIb
      positive neutrophils. A family study showed that the infant's mother, one of the
      mother's sisters, and her mother were Fc gamma RIIIb deficient. No neutrophil
      antibodies were found in the plasma from these other Fc gamma RIIIb-negative
      women, although both had had numerous pregnancies. The three women were healthy,
      but one had recurrent otitis. DNA analysis of the family showed the absence of
      both Fc gamma RIIIB genes in the three Fc gamma RIIIb-negative women. The father
      of the child and all the children of the Fc gamma RIIIB gene-deficient women were
      shown to lack one of the Fc gamma RIIIB genes. CONCLUSION: A new case of
      isoimmune neonatal neutropenia caused by anti-Fc gamma RIIIb is identified. The
      family study indicates that the Fc gamma RIIIb deficiency is a hereditary genetic
      defect. In accordance with the location of Fc gamma RIIIB on chromosome 1, an
      autosomal pattern of inheritance of the Fc gamma RIIIB-deficient allele was
      observed.

PMID- 7631411
TI  - Posttransfusion purpura following bone marrow transplantation.
AB  - BACKGROUND: Thrombocytopenia is a major cause of morbidity and hospital expense
      following bone marrow transplantation. Platelet transfusions in these patients
      are frequently complicated by the recipient's development of antibodies to HLA
      class I antigens. When these patients become refractory to the transfusion of HLA
      matched platelets, the recipient's platelet antigen phenotype must be determined,
      to ensure that donor platelets will be phenotypically compatible. Cases of
      alloimmunization to HPA-1a and HPA-1b resulting in refractoriness to transfused
      platelets and the subsequent development of a posttransfusion purpura-like
      syndrome are reported. CASE REPORTS: In the first case, a 43-year-old woman with
      Stage IV infiltrating ductal breast cancer presented to the hospital for a
      transplant of autologous peripheral blood stem cells. After the transplant, her
      platelet count remained less than 10 x 10(9) per L, despite daily platelet
      transfusions, including HLA-matched platelets. Fourteen days following the
      transplant, her serum was found to contain anti-HPA-1a. Initially, the patient
      was refractory to the transfusion of HPA-1a-negative platelets, but after
      treatment with intravenous immunoglobulin, she had transient increases in
      posttransfusion platelet counts. She was also treated with a staphylococcal
      protein A immunoadsorption column and has not had any such subsequent
      refractoriness. Her genotype has been found, by use of allele-specific
      oligonucleotide hybridization with white cell DNA, to be HPA-1b/1b. The second
      case involved a 32-year-old woman with chronic myelogenous leukemia who received
      an unrelated-donor marrow transplant. Three years later, her CML recurred, and
      she was treated with interferon-alpha. Four months afterward, she experienced
      interferon-alpha-induced thrombocytopenia and the interferon therapy was
      discontinued. She received 12 platelet transfusions in 20 days, but none was
      effective. Antibodies specific for HLA antigens and HPA-1b were detected, and
      three HLA-matched, HPA-1b-negative apheresis platelet components were given, but
      without effect. Two days after treatment with methylprednisolone (1 g
      intravenously) and prednisone (2 mg/kg/day orally), her platelet count was 26 x
      10(9) per L, and after 8 more days, it was 102 x 10(9) per L, without further
      transfusions. She was found to be homozygous for HPA-1a (HPA-1a/1a). CONCLUSION:
      Anti-HPA-1a and anti-HPA-1b can cause refractoriness to platelet transfusions in
      bone marrow transplant patients. Testing for platelet-specific antibodies should
      be considered in all patients who are refractory to HLA-matched platelets.

PMID- 7631413
TI  - Transfusion alert: use of autologous blood. National Heart, Lung, and Blood
      Institute Expert Panel on the use of Autologous Blood.

PMID- 7631412
TI  - Questions to be answered regarding umbilical cord blood hematopoietic stem and
      progenitor cells and their use in-transplantation.

PMID- 7631414
TI  - Medical necessity--a threat to treatment of chronic disease.

PMID- 7631415
TI  - Mathematical analysis of isovolemic hemodilution.

PMID- 7631416
TI  - Polyethylene glycol in autoadsorption of serum for detection of alloantibodies.

PMID- 7631417
TI  - Cytochrome f revealed.

PMID- 7631418
TI  - Electrospray mass spectrometry for protein characterization.
AB  - Mass spectrometry is a venerable analytical tool that has been used for some time
      in biochemistry for the analysis of small molecules, such as steroids. More
      recently, physicists have solved the problems associated with vaporizing and
      ionizing proteins and peptides, thereby allowing mass spectrometry to take on new
      roles in investigating protein sequences, structures and modifications.

PMID- 7631419
TI  - Common sequence and structural features in the heat-shock factor and Ets families
      of DNA-binding domains.

PMID- 7631420
TI  - On the origin of a silencer.
AB  - Although there are several compelling pieces of evidence suggesting that
      transcription can promote DNA replication, there are few studies that indicate a
      role for DNA replication in controlling transcription. Here, we discuss the role
      of the HMR-E silencer, an origin of replication that plays a crucial role in the
      regulation of expression of mating-type genes in the yeast Saccharomyces
      cerevisiae.

PMID- 7631421
TI  - PKR: a new name and new roles.
AB  - The double-stranded RNA (dsRNA)-activated protein kinase, now called PKR, was
      first discovered by virtue of its ability to phosphorylate translation initiation
      factor eIF-2 and inhibit its activity. Recent studies have shown that expression
      of inactive mutants of PKR in cultured cells causes them to acquire
      characteristics typical of transformed cells. These and other findings indicate
      that PKR plays a role in the normal control of cell growth and differentiation.
      It seems likely that, in addition to eIF-2, PKR has other substrates including
      the protein I-kappa B, which regulates the transcription of certain genes.
      Indeed, it now seems likely that PKR mediates the regulation of selected genes by
      dsRNA.

PMID- 7631422
TI  - Upgrade blues.

PMID- 7631423
TI  - Methods and reagents. Electro-transformation of Escherichia coli with plasmid
      DNA.
AB  - Methods and reagents is a unique monthly column that highlights current
      discussions in the newsgroup bionet.molbio.methds-reagnts, available on the
      Internet. This month's column discusses some reasons for switching to
      electroporation to transform bacteria with plasmid DNA. For details on how to
      partake in the newsgroup, see the accompanying box.

PMID- 7631424
TI  - [The reaction of anterior hypothalamic nuclei and of the endocrine glands to the
      administration of staphylococcal peptidoglycan].
AB  - The results of investigation of the influence of Staphylococcus peptidoglycan on
      supraoptic (SON) and paraventricular (PVN) hypothalamic nuclei, adrenal and
      thyroid glands of CBA mice was studied. Alterations in the SON and PVN secretory
      cells were found. The percentage of neurocytes that actively synthesize and
      secrete the Gomori [correction of Homory]-positive substance increased.
      Biosynthetic functions and secretion of the hormone was enhanced. In adrenal
      glands, alterations were found only in the bundled zone.

PMID- 7631425
TI  - [Clinico-genealogical and genetic-mathematical research on cancer of the cervix
      uteri].
AB  - Analysis of the family histories of 179 patients with cancer of uterine cervix
      was conducted to detect the influence of their heredity and environmental factors
      on the development of malignant tumors using clinical-genealogical and genetic
      mathematical methods. Decomposition of phenotypic variance was used as a basis
      for detecting the contribution of genetic component (2.92%) and random
      environmental component (97.08%) which reflected the influence of exogenic risk
      factors of development of uterine cervix cancer. Clinico-genealogical analysis of
      probands' pedigrees was the basis for detecting association of malignant
      neoplasms in lung and uterine cervix epithelia.

PMID- 7631426
TI  - [The genetic and demographic structure of the population of Poltava].
AB  - It was detected that the migration coefficient of Poltava's population increased
      from m = 0.68 in 1960 to 0.71 in 1985. The coefficient of coincidence of married
      pairs in nationality and origin decreased from K = 0.152 and K = 0.055 to K =
      0.119 and K = 0.043 and increased from K = 0.085 to 0.095 according to their
      occupation. Potential selection index comprised I = 0.1798.

PMID- 7631427
TI  - [An analysis of human genome expression by using libraries of the cDNA from
      different organs].
AB  - The major liver and brain transcripts having different specificity of expression
      were isolated and characterized by differential hybridization of human fetal
      liver and human fetal brain cDNA libraries with total cDNA probes from different
      human tissues. The sequencing and analysis of nucleotide sequences indicated that
      the most isolated cDNA clones have contained unknown genes.

PMID- 7631428
TI  - [An analysis of the genetic structure of a hybrid population of green frogs, Rana
      esculenta complex, from the flats of the Danube].
AB  - Analysis of genetic structure of geographically isolated population of hybrid
      complex Rana esculenta L. from Danube delta according to a complex of biochemical
      gene markers was conducted. A parental species of Rana ridibunda and hybrids
      ridibunda-lessonae of the first generation only were found in the population. The
      complete absence of genetic recombination and introgression of genes from the
      locus Ldh-B, which was found in Dnieper populations, is characteristic of the
      population. The differences observed may be explained by genetic nonuniformity of
      geographical forms of R. lessonae. This forms may have taxonomic differences.

PMID- 7631429
TI  - [The ultrastructure of the pinealocytes of the epiphysis cerebri (pineal body) in
      mammals].
AB  - The detailed description of ultrastructure of pinealocytes, the main hormone
      producing cells, is presented. The new data concerning vacuolar and vesicular
      structures, as well as intercellular interaction of pinealocytes are also
      presented. The state of the problem of investigation of different ultrastructural
      types of pinealocytes and problems of response of subcellular structures of
      pinealocytes on exo and endogenic factors are discussed.

PMID- 7631430
TI  - Primitive neuroectodermal tumors: ultrastructural and immunohistochemical
      studies.
AB  - We report here ultrastructural and immunohistochemical studies of neuroblastic
      differentiation in the retrospective (n = 17) and prospective (n = 26) series of
      primitive neuroectodermal tumors (PNETs). By electron microscopy, neuritelike
      structures containing parallel-oriented microtubules, adhesive plaque junctions,
      and pleomorphic dense-core vesicles were found in the majority of tumor specimens
      while synaptic specializations were very rare. By immunohistochemistry,
      synaptophysin appeared to be the most reliable marker for neuroblastic
      differentiation present in the most reliable marker for neuroblastic
      differentiation present in the majority of tumors, while 200 kDa neurofilament
      protein was immunovisualized in a lower proportion of tumors. Glial fibrillary
      acidic protein (GFAP) was expressed in both reactive astrocytes and in a small
      proportion of otherwise typical neoplastic cells. We conclude that the majority
      of PNETs revealed diverse differentiation and that electron microscopy is still
      the most reliable tool for its detection followed by immunohistochemistry for
      synaptophysin.

PMID- 7631431
TI  - X-ray microanalysis of peripheral lung carcinomas.
AB  - A total of 15 cases of peripherally located lung carcinomas associated with scar
      (scar carcinoma) were studied by light microscopy and electron microscopy with
      energy-dispersive X-ray microanalysis (XMA). Results were compared to those of
      three autopsy lungs without significant pulmonary findings that served as
      controls. Fibrosis with scar formation characterized the 15 tumor cases.
      Particulate depositions including doubly refractile particles were also increased
      in the tumor group. XMA identified 25 elements with great complexity of
      particulate composition. Silicon was the most prominent element and was found in
      16 of 18 cases studied. Kaolinite, feldspar, talc, muscovite, and silica were
      recognized. The fibrogenic properties of silicate compounds were emphasized,
      including their prominence in the lung tumor group. While the important concept
      of tumor desmoplasia was recognized, the study showed significant fibrosis in
      relation to fibrogenic materials, which undoubtedly preceded the appearance of
      the tumors. Also noted were the carcinogens uranium, cadmium, chromium, nickel,
      and arsenic, some of which were previously described as minor constituents of
      naturally occurring minerals.

PMID- 7631432
TI  - High-resolution ultrastructural study of the rat glomerular basement membrane in
      long-term experimental diabetes.
AB  - The ultrastructure of the glomerular basement membrane of the long-term diabetic
      and age-matched control rats was studied with the application of advanced high
      resolution microscopy. By using the freeze substitution method for the
      preparation of the renal tissue, it was possible to observe that the glomerular
      basement membrane in control and diabetic animals is composed on only a single
      lamina densa without the presence of a lamina lucida interna or externa. High
      resolution electron microscopy of the diabetic glomerular basement membrane
      showed significant alterations in its morphology and ultrastructure. First, the
      basement membrane in diabetic condition appeared to be split into two halves,
      endothelial and epithelial. In the epithelial half of the membrane, the network
      of distinct strands referred to as cords, which were clearly present in the
      glomerular basement membrane of age-matched control animals, became less distinct
      and showed a diffused appearance being evenly replaced by thin filaments. The
      openings of the network were filled with a granular material. In the endothelial
      half of the membrane, on the other hand, the cord network was variably lost in
      diabetic condition and, within the resulting vacant spaces, bundles of fibrils 12
      nm in width, identified as basotubules, were deposited. Immunolabeling for type
      IV collagen was found to be enriched in the endothelial half of the basement
      membrane being associated with the bundles of basotubules. The ultrastructural
      changes reported by high-resolution microscopy could be related to the molecular
      alterations of the basement membrane components and to the loss in
      permselectivity occurring during diabetes.

PMID- 7631433
TI  - Refractoriness of the immature rat epididymis to the early cadmium lesion.
AB  - Ninety minutes after i.p. injection of 3 mumol of cadmium chloride/100 g body
      weight into immature, 15 day-old rats, the endothelial intercellular junctions of
      the caput epididymis capillaries showed none of the lesions such as loss of
      junctional associated ectoplasmic microfilaments, separation of interdigitated
      leaflets, disassembling of interendothelial tight junctions, passage of blood
      plasma and cells into the pericapillary space, platelet clumping and
      disintegration, and intracapillary clotting, which after the same dose are found
      in sexually mature rat epididymides. The resistance of the immature,
      physiologically intraabdominal epididymal capillary endothelium reminds one of
      the protection against cadmium that is brought about by surgical cryptorchidism
      in adult mature rats. We suggest that either local enzyme immaturity or the
      abdominal temperature (5 degrees C than scrotal temperature) may protect zinc
      enzymes against displacement by cadmium.

PMID- 7631434
TI  - Ciliated renal tubular cells in crescentic glomerulonephritis.
AB  - Numerous cilia were found in the proximal convoluted tubules from a case of
      crescentic glomerulonephritis. The cilia exhibited the 9 + 2 pattern of
      organization characteristic of motile cilia. Microvilli were scanty or absent in
      heavily ciliated cells. The significance of renal cilia is discussed.

PMID- 7631435
TI  - Case for the panel. Unique intracytoplasmic inclusion in a probable granular
      renal cell carcinoma metastasis.

PMID- 7631436
TI  - [Morphine--paradoxes about a known agent].

PMID- 7631437
TI  - [Synovectomy in rheumatoid arthritis].
AB  - Surgical synovectomy in the treatment of rheumatoid arthritis has been performed
      for more than a 100 years, and yet the definite indication has not been made
      clear. Synovectomy has a convincing, but mostly time-limited effect on pain and
      articular hydrops, but the radiological progression continues almost undisturbed.
      Histological evaluation of the regenerating synovial membrane has now shown a
      tendency towards reversing to baseline within about a year. The difficulties in
      evaluating the operation are caused by the lack of comparable randomized studies
      performed on large populations, treated in a double-blind fashion and examined in
      cooperation between surgeon and rheumatologist.

PMID- 7631438
TI  - [Focus group interview as a qualitative research method].
AB  - Focus group research is a qualitative method with interesting properties. It is
      performed by planned discussion and interview with a small group of people
      conducted by a moderator. The participants are sampled from the study population.
      The aim is to obtain knowledge of the participant's considerations and ideas on a
      specific topic. The method is feasible in illuminating the variation of
      viewpoints held in a population. It is used as a single source of data or in
      combination with other methods. As the method provides data in a social context
      it is used as an alternative to individual interviews, when appropriate, or in
      the initial development of a questionnaire. The focused interviews is feasible in
      methodological triangulation or when other methods are suboptimal. Focus group
      interviews is considered to be of value in health research.

PMID- 7631439
TI  - [Compulsory procedures in the treatment of somatic diseases in mentally ill
      patients].
AB  - The Danish law concerning commitment and compulsory procedures in psychiatry was
      reformed in October 1989, and for the first time laid down regulations for
      compulsory treatment of somatic disease in psychotic patients. The aim of the
      study was to evaluate whether the law is useful in clinical practice. The course
      of 28 psychotic patients who were committed and/or compulsorily treated due to
      severe somatic disease is described. We conclude that the law is a useful tool in
      the acute treatment of life-endangering somatic disease in psychotic patients.

PMID- 7631440
TI  - [Albuminuria in persons with real hypertension, white coat hypertension and
      normotension].
AB  - A prospective comparison of office blood pressure, daytime ambulatory blood
      pressure and urinary albumin excretion was performed in 284 consecutive patients
      from general practice with newly diagnosed, untreated mild to moderate
      hypertension. Based on daytime ambulatory blood pressure 173 were classified as
      established hypertensives and 111 as white coat hypertensives. A sample of 127
      subjects drawn from the Danish national register served as a normotensive control
      group. It was found that urinary albumin/creatinine ratio differed significantly
      between the three groups; the difference remained significant after correction
      for covariables. Early morning urine albumin/creatinine ratio was weakly but
      significantly correlated to blood pressure. Early morning urine
      albumin/creatinine ratio was as reproducible a measure as 24-hour albumin
      excretion. It is concluded that white coat hypertensive patients have less renal
      involvement than patients with established hypertension, but more than a
      normotensive control group.

PMID- 7631441
TI  - [Necrotizing enterocolitis. Occurrence in Western Denmark].
AB  - We reviewed the clinical presentation, subsequent course and outcome of 45
      newborn infants with neuotizing enterocolitis (NEC) seen on eight neonatal
      intensive care units during a 10 year period (01.01.82-31.12.91). The average
      incidence of NEC was found to be 1.2 (0.3-3.8) per 10,000 liveborn infants with a
      tendency to increase during the period. Eighteen percent had a birth weight of
      less than 1,000 g. Thirty-six percent had a birthweight between 1,000 and 1,500
      g. Twenty-nine percent had a birthweight between 1,500 and 2,500 g. The last
      group made up of 16% had birth weights above 2,500 g. The mortality was
      determined by the severity of the disease, being 0% for infants within Bell's
      stage I, 25% in Bell's stage II and 71% in Bell's stage III. Sixty-nine percent
      of the infants were diagnosed in stage III, probably because of low attention to
      NEC in its early stages. The prognosis of surviving infants was good with no
      gastrointestinal symptoms when evaluated four to five years later.

PMID- 7631442
TI  - [Monitoring of respiration at night. Evaluation of a microprocessor-based system
      for cellection, analysis and presentation of respiratory parameters].
AB  - Spirolab, a microprocessor-based system, intended for collection, analysis and
      presentation of respiratory parameters was validated by comparing measurements in
      the oesophagus end stomach with changes of resistance in strain-gauges placed on
      the thorax and abdomen. It was also shown that temperature changes can be used
      for monitoring airflow. The limitations of the methods are discussed. Spirolab
      and its monitoring methods have proven suitable and valid in the diagnosis and
      control of treatment of patients with nocturnal respiratory disorders.

PMID- 7631444
TI  - [Scintigraphic demonstration of bleeding colonic metastasis in a patient with
      endometrial cancer].
AB  - Detection of gastrointestinal bleeding by means of radiotracers is a non-invasive
      method, and should be considered when endoscopy and barium radiography have
      failed to identify the focus. The two most prominent tracers are 99mTc sulphur
      colloid and 99mTc red blood cells, and both detect lower gastrointestinal
      bleeding with at least the same sensitivity as angiography. A case of
      gastrointestinal bleeding in a 68-year old woman is presented. The bleeding
      source in the colon was precisely identified with the 99mTc RBC method, and was
      later shown to be a metastasis from her endometrial cancer.

PMID- 7631443
TI  - [Postulosis palmoplantaris caused by angiotensin-converting enzyme inhibitors].
AB  - Angiotensin-converting enzyme (ACE) is identical to kinase II, which inactivates
      bradykinin. Inhibition of bradykinin degradation by ACE inhibitors alters the
      kinin-kallikrein arachidonic acid system leading to increased concentrations of
      inflammatory metabolites. It has previously been demonstrated that the
      arachidonic acid system may play a role in the pathogenesis of psoriasis/volar
      pustulosis. Our patient was treated with Captopril and developed a rash identical
      to volar pustulosis within six weeks. Captopril was substituted with Perindopril,
      and the eruptions had almost disappeared five months later after a short systemic
      treatment with steroids. One month later the patient developed the same rash.
      Perindopril was withdrawn and the eruptions had disappeared two months later.

PMID- 7631445
TI  - [Paracetamol poisoning].

PMID- 7631446
TI  - [Diagnosis of pyruvate kinase deficiency].

PMID- 7631447
TI  - [Carbon monoxide in our buildings].

PMID- 7631448
TI  - [The national patient registry. Evaluation of data quality].
AB  - The Danish National Patient Register, which includes information on all patients
      admitted to hospitals, has been evaluated as concerns the quality of the data
      included. The material examined consisted of a representative sample of 1094
      patients from departments all over the country (gynaecology and obstetrics,
      medicine, surgery and paediatrics). Recoding of data, clinical as well as
      administrative, based on copies of the case records from the hospitals was
      carried out by two clinically working physicians (registrars). For the
      administrative data e.g. length of stay, satisfactory concordance was found. The
      validity of clinical information depended on clinical speciality and degree of
      diagnostic specificity. Based on the international classification the agreement
      on the three digit diagnostic level was better than on the five digit diagnostic
      level. For surgery the agreement was better than for medicine. The agreement
      between the diagnostic information (primary diagnosis) and the recoder in
      choosing primary diagnosis varied from 66-83 percent on the five digit level and
      between 73-89 percent on the three digit diagnostic level. If cases where the
      diagnosis in the registry could be regarded as an acceptable alternative were
      included, the agreement between the registry and recoding was 75-90%. In a
      subsample of the material double coding by the two coders was carried out and it
      was remarkable that, taken as a whole, the degree of agreement between the two
      coders was of the same size as between recoder and the registry. It is
      anticipated, however, that introduction of ICD-10 with more clear-cut rules for
      choice of primary diagnosis in morbidity coding will contribute to better
      validity and consequently improved hospital statistics.

PMID- 7631449
TI  - [Intraobserver variation in the classification of diseases].
AB  - The aim of this study was to describe the variation within the observer in
      classification of diseases, with special regard to pregnancy, birth and
      maternity. Four observers A, B, C and D classified 150 random cases of pregnancy,
      birth and maternity on two different occasions with six months interval. The rate
      of agreement within the observer between the two different occasions was
      evaluated. The average agreement rate was 86% (71-92%) concerning diagnoses of
      pregnancy. 90% (84-95%) concerning maternity and 65% (53-75%) concerning
      delivery. The diagnostic spectrum of the observers and their criteria for the use
      of diagnoses were variable. The amount of variation correlated to the number of
      diagnoses and poorly defined diagnostic criteria. In conclusion, great variation
      was found within the observer in classifying diseases, especially concerning
      delivery, due to increased numbers of diagnoses and poorly defined diagnostic
      criteria. The setting-up of branch specialist committees is recommended, if we in
      the future want to use a public diagnostic register as a tool for research. These
      committees must achieve consensus concerning the need for classification within
      each specialty, define criteria for diagnosis and communicate recommendations and
      education in the system of classification.

PMID- 7631450
TI  - [Calcium channel blockers (calcium antagonists). Background, effects and use].
AB  - The calcium ion plays a decisive role in the effect and regulation of several
      cellular processes. The heart muscle cells, pacemaker and channel systems and
      vascular smooth muscle are functionally dependent on Ca2+ influx mainly via
      potential sensitive L (long lasting)-Ca(2+)-channels, which are blocked by Ca(2+)
      channel blockers, a group of organic substances binding to specific sites at the
      Ca2+ channels. The Ca2+ channel blockers are now well established in the
      treatment of angina pectoris, arterial hypertension, supraventricular arrhythmia
      and subarachnoidal haemorrhage. On the basis of chemistry and pharmacodynamics
      the Ca2+ channel blockers are divided into three groups, with verapamil,
      nifedipine and diltiazem representing 1. generation derivatives and prototypes
      for groups I, II and III, respectively. All Ca2+ channel blockers act as
      vasodilators, while group I (verapamil) and to a lesser degree group III
      (diltiazem) also have antiarrhythmic effects. All Ca(2+)-channel blockers are
      contraindicated in hypotension. In cases of pronounced bradycardia, sinoatrial
      and atriventricular block Ca2+ channel blockers with antiarrhythmic effects are
      contraindicated and must be used with care in combination with beta-blocker
      treatment and in heart failure. Headache, flushing, reflex tachycardia, nausea,
      obstipation and ankle oedema are the most important secondary effects. With
      respect to pharmacodynamics the newly marketed 2. generation derivatives do not
      differ essentially from the 1. generation derivatives. The clinical potential of
      the Ca2+ channel blockers is not fully explored and the possibilities for
      extending their indications are still to be elucidated.

PMID- 7631451
TI  - [Glomerular tip lesions--a newly described glomerular change].
AB  - Glomerular tip lesion is a newly described histopathological lesion characterized
      by a focal and segmental widening of the mesangial matrix without
      hypercellularity together with capillary dilatation, hyaline exudation on the
      inside of capillary walls and occurrence of vacuolized cells, localized to the
      peripheral segments of the glomerular tuft. Clinically, these patients have a
      pronounced nephrotic syndrome with slightly reduced renal function, but terminal
      renal failure is seldom seen, even after many years of disorder. Two
      characteristic case histories are presented. The classification of this lesion
      among the glomerular disorders is at present uncertain. It may represent a
      transitional form between minor lesion nephritis and focal segmental sclerosis, a
      separate disorder, or a functional lesion associated with high proteinuria.

PMID- 7631452
TI  - [Waiting lists--how valid are the official numbers? Evaluation of a waiting list
      at a department of orthopedic surgery].
AB  - With increasing waiting lists for admission to hospital, the aim of this study
      was to investigate the reliability of an orthopaedic waiting list. Questionnaires
      were sent to every patient listed as waiting for more than three months. The
      questionnaire addressed the current symptoms and the current need for surgical
      treatment. In case of no reply, a further evaluation was done before eventual
      removal from the waiting list. Of 809 questionnaires mailed, replies were
      received from 409. A total of 376 were removed from the list, including 111 due
      to registration errors in the central data base. This study has shown how the
      indication for operation changes during the waiting period but also that
      information from data bases can be most unreliable. We find the reasons so
      general, that we recommend a corresponding evaluation of other waiting lists.
      Altogether, today's waiting list is faulty and thus provides a wrong basis for
      management.

PMID- 7631454
TI  - [Hemifacial spasms--clinical picture, diagnosis and treatment].
AB  - A rectrospective study of 23 consecutive patients with hemifacial spasm is
      presented. Based on this experience, a practical approach to the diagnosis,
      investigation and treatment with injections of botulinum toxin is described.
      Magnetic resonance imaging angiography of the brain was performed in 20 patients
      an 15 controls. Contact between an artery from the vertebrobasilar circulation
      and the intracranial part of the facial nerve was observed ipsilaterally to the
      spasm in 17 patients (85%) and in two controls (7%). Treatment with botulinum
      toxin was performed in 16 patients with moderate to good improvement in the
      majority of the patients. MR-angiography is recommended in order to exclude
      infrequent etiologies and as preoperative evaluation. Botulinum toxin injection
      is recommended as the symptomatic treatment of choice. The possibility of
      curative surgical intervention by microvascular decompression of the facial nerve
      is discussed.

PMID- 7631453
TI  - [Significance for prognosis of delayed diagnosis and treatment of breast cancer].
AB  - In a study of 7608 patients with primary breast cancer the effect of patient's
      and doctor's delay on survival was examined. The delay was arbitrarily divided
      into the following intervals: Short (0-14 days), intermediate (15-60 days) and
      long (> 60 days). The delay had significant influence on survival. A long
      patient's delay was associated with an unfavourable outcome, as compared with a
      short delay. On the contrary, the prognosis was better for patients with a long
      doctor's delay compared to that of a short doctor's delay. Overall, when
      corrected for age, the prognostic value of delay in terms of mortality increased
      by 24% for a long patient's delay compared to a short one, and by 13% for a short
      doctor's delay compared to a long one. This suggests that all causes of delay
      should be kept at a minimum.

PMID- 7631455
TI  - [Inhalation of levopromazine (Nozinan) in the treatment of status asthmaticus].
AB  - Levomepromazine reduces histamine-induced bronchial hyperresponsiveness in
      asthmatics without significant sedation. We present two patients with acute
      asthma refractory to conventional therapy, who were treated with inhalation of
      2.5 mg levomepromazine. Until controlled studies have been done, we suggest that
      inhalation of levomepromazine be restricted to patients with asthma refractory to
      conventional therapy.

PMID- 7631456
TI  - [Cutaneous myiasis--an imported case caused by the South American fly larvae
      Dermatobia hominis].
AB  - Cutaneous myiasis is the infestation of skin or mucous membranes with larvae of
      flies. We describe a case caused by Dermatobia hominis, acquired in South
      America. Cutaneous myiasis should be suspected in a patient with a secreting, non
      healing furuncular skin-lesion and relevant travel history. The patient may
      remember being bitten by insects. Sensation of movement in the lesion, which may
      be observed, supports the diagnosis. Correct diagnosis will prevent unnecessary
      treatment with antibiotics, and surgery will almost always prove unnecessary.

PMID- 7631457
TI  - [Biomedical and biotechnological programs of the EEC].

PMID- 7631458
TI  - [Chronic membranous glomerulonephritis and treatment with cytostatic agents].

PMID- 7631459
TI  - [The Scandinavian Simvastatin Survival Study (4S): old wine in new bottles].

PMID- 7631460
TI  - [Sun lotion and malignant malanoma].

PMID- 7631461
TI  - [New drugs 1988-1993--a review of the number, types and share of total
      utilization].

PMID- 7631462
TI  - [Diagnostic endoscopy in pediatric rhinology].
AB  - The paper provides a description on indications to diagnostic endoscopy, its
      techniques, specific pediatric features, types of anesthesia. Typical
      complications are specified. Emphasis is placed on local developmental defects of
      the nasal cavity, lateral wall in particular, as they interfere with natural
      sinus drainage in many children with chronic and recurrent sinusitis, chronic
      rhinitis. The tables detail variants of the above deformities with specification
      of the likely site of stenosis in so-called osteomeatal zone. It is believed that
      minor surgical correction in the above zone is more preferable than extended
      radical operations. This seems important in pediatric practice.

PMID- 7631464
TI  - [Role of the labyrinthine artery in the development of sensorineural hearing
      loss].
AB  - 8 patients with acute neurosensory hypoacusis (NSHA) and 8 patients with chronic
      NSHA were examined clinically, otoneurologically, underwent rheoencephalography,
      dopplerography, vertebral digital subtraction angiography according to Stenvers.
      There existed no changes in the major vertebrogenic vessels, but blood flow along
      the artery of the labyrinth was slow, the artery itself was either noncontrast or
      identified by the basilar artery branch, i.e. presents as a long thin vessel
      easily responsive to each factor producing vibration. Severe chronic cochlear
      NSHA occurs more frequently in patients in whom angiography fails to register the
      artery of the labyrinth. The latter is recorded in cases of acute acalar NSHA.
      The latter patients have more favourable prognosis in respect to hearing
      thresholds. Thus, NSHA patients have anatomical or pathological abnormalities
      influencing the disease degree and clinical course.

PMID- 7631465
TI  - [Pathogenetic aspects of otosclerosis].
AB  - Basic otosclerosis pathogenetic factors are reviewed with a special emphasis on
      heredity. The inheritance in otosclerosis is autosomal dominant with incomplete
      gene expression. The involvement of HLA antigens is detailed. Autoimmune origin
      of the disease is confirmed morphologically and immunologically in perilymph and
      serum tests. There are infiltrates with lymphocytes, plasmatic and mast cells in
      basis stapedial mucoperiostal tissue. Perilymph contained significantly elevated
      levels of IgG and IgM, of antibodies to native DNA and type II collagen,
      especially in patients with active otosclerotic foci. Validation of relevant
      etiopathogenetic mechanism is provided basing on first-hand experience and
      literature data.

PMID- 7631463
TI  - [Time aspects of short-latency acoustic evoked potentials in cleaners-up after
      the Chernobyl AES accident who have voice disorders].
AB  - Brain stem SLAEP were compared to EEG readings in patients with vocal problems
      consequent to low-dose radiation received after the Chernobyl accident. Versus
      control subjects, the patients had significantly (p < 0.01) longer latent periods
      of SLAEP waves 11 and V as well as the interpeak interval I-V. EEG findings
      indicated in patients changes in the diencephalic and diencephalic-stem regions,
      CNS dysfunction in the form of cortical structure irritation in the presence of
      low cerebral bioelectric activity. As shown by objective methods, the above
      patients with vocal problems have CNS disorders. This should be taken into
      consideration in planning treatment and incapacity decisions for such subjects.

PMID- 7631466
TI  - [Function of acoustic analyzer in multiple sclerosis in exacerbation].
AB  - Audiometric examination of 51 patients with aggravated multiple sclerosis
      included pure-tone threshold audiometry, assessment, of speech intensity
      function, of adaptation, masking, sound laterality, impedance tympanomanometry,
      perception of complicated speech, registration of short-latency acoustic evoked
      potentials. Acoustic analyzer disfunction, especially that of sound laterality,
      was discovered in 42-83% and 68% of patients, respectively. The hearing system
      was affected most frequently at the level of brain stem and occasionally at the
      level of the cochlea (15%). Sorption detoxication therapy produced response in
      100% of patients by subjective and neurological criteria, while only in 59% by
      acoustic criteria. This disagreement is likely to reflect subclinical symptoms
      and may represent a prognostic value.

PMID- 7631467
TI  - [Effectiveness of computerized tomography of the temporal bone in the diagnosis
      of chronic suppurative otitis media].
AB  - Temporal bone computed tomography findings were compared to those obtained at
      operation in 30 patients with chronic OMP. The comparison demonstrated high
      informative value of CT examinations which provide exhaustive characteristics of
      the pathological process important for preparation to and performance of relevant
      surgery.

PMID- 7631468
TI  - [Cellular histamine and bradykinin receptors in the larynx and trachea. I].
AB  - Classic physiological and pharmacological experiments were made on 33 rabbits
      under hexenal anesthesia to determine the presence, topical concentration and
      activity of H2 and B2-receptors. These parameters were inferred by edema and
      other vascular responses of the mucosa to local application of histamine and
      bradykinin prior to and after usage of specific blocker of each receptor type.
      Both mediators and receptor blockers were applied to laryngeal and tracheal
      mucosa for 10 min (histamine 10(-4) and 10(-3) g/ml, H2-receptor blocker
      metiamide 0.1 and 1 mmol, bradykinin 10(-5) and 10(-4) g/ml, B2-receptor blocker
      pyridinolcarbamate 10(-2) and 10(-1) g/ml). The larynx and trachea were found to
      contain H2- and B2-receptors the concentrations of which were greater in the
      subvocal part of the larynx than in the vestibular part and trachea. B2-receptor
      activity and concentrations in the subvocal part of the larynx were 10 times
      while in the trachea 1.5-2 times greater than those of H2-receptors. These
      regularities were not influenced by individual varieties of receptor topical
      concentrations. The blocker density in the receptors and the duration of their
      binding were not universally proportional. This is also true for the relations
      mediator-receptor. Concentrations and activity of H2- and B2-receptors are
      thought important in pathogenesis and location of acute inflammatory and allergic
      conditions in the upper respiratory tract.

PMID- 7631469
TI  - [Surgical aspects of recovery of vocal function after radical removal of the
      larynx in cancer].
AB  - The paper is devoted to surgical procedures aimed at voice reestablishment in
      patients without larynx removed for cancer. Original surgical techniques
      practiced by the authors are proposed: tracheoesophageal shunt with creation of
      the defense valve from the esophageal mucosa, esophagus and lower lip
      mucomuscular graft, bypass repair. The procedures were used in 79 patients with
      removed cancer-affected larynx. Vocal function recovery occurred in 90%, the
      defense function restored in 80% of the patients treated.

PMID- 7631470
TI  - [Endoscopic study on the effects of controlled pressure on the mucosa of the
      nasal cavity and paranasal sinuses].
AB  - Endoscopy with fiber endoscope Olimpus FNL-10 was performed to study the effects
      of controlled pressure on nasal mucosa. In 15 patients with aggravated chronic
      purulent sinusitis maxillary mucosa alterations were assessed using sinus
      catheter and maxillary microsinusotomy. 12 patients with the same diagnosis
      underwent nasal mucosa examination with sinus catheter . The experiments with
      controlled pressure in the nasal cavity and paranasal sinuses demonstrate that
      the above pressure causes no damage to the mucosa, though it enhances hyperemia
      and diminishes edema in the area of osteomeatal complex as a result of changing
      the pressure (+) and (-).

PMID- 7631471
TI  - [Changes in the mucous membrane of the upper respiratory tract and the immune
      status in phosphorus poisoning].

PMID- 7631472
TI  - [A experimental device for ultrasonic control of ear ossicle prosthesis
      function].
AB  - A device designed by the author is intended for functional control over
      prosthetic auditory ossicle efficacy in experiment. The device employs Doppler
      effect and lies inside the frame adjusted for the experimental conditions. The
      device provides standard conditions for determining amplitude-frequency
      characteristics and signal transmission factor in the range 128-2000 Hz. As
      illustration, measurements of transmission from the T-shape prosthesis are
      described.

PMID- 7631473
TI  - [Use of clofelin as an anesthetic and component of neurovegetative defense in ENT
      oncologic surgery].
AB  - Metabolism indices (blood sugar, lactic acid, pyruvic acid) and hemodynamics
      (mean arterial pressure, 1-hour diuresis) were measured in 41 hypertensive
      subjects undergoing resection or removal of the larynx for cancer under
      endotracheal anesthesia through tracheostoma. 18 patients of group 1 received
      calypsol anesthesia, whereas 23 patients of group 2 received combination of
      calypsol with clofelin. Croup 2 patients benefited more because clofelin
      potentiated the analgetic effect of calypsol, intensified neurovegetative block,
      promoted more rapid recovery of normal respiration, prolonged analgetic effect in
      postoperative period.

PMID- 7631474
TI  - [Changes in the cartilage shape under the action of laser irradiation].
AB  - Investigations of structural and mechanical properties of cartilage tissue
      exposed to laser radiation have shown the effect of laser relaxation of the
      tension existing in the cartilage and changes in the latter form to be due to
      phasic transition of water from bound into free state. Laser radiation does not
      induce macroscopic transformations of the matrix structure. New form of the
      cartilage proved stable this offering new prospects for wide application of this
      technique in otorhinolaryngology and plastic surgery.

PMID- 7631475
TI  - [Method of flow lavage of the frontal sinus after frontotomy].

PMID- 7631476
TI  - [Prognosis of the course of puncture-treated maxillary sinusitis by cytological
      features of the lavage fluid].
AB  - The cytological picture of the lavage fluid obtained at puncture treatment of
      maxillary sinusitis provides a sufficient objective characterization of the
      inflammation in the sinuses. This makes it easier to predict the disease outcome
      and progression. The technique is simple and can be performed in any medical
      institution furnished with clinical laboratory.

PMID- 7631477
TI  - [Clinical use of YAG-Nd-laser in otorhinolaryngology].

PMID- 7631478
TI  - Effects on sheep of transport by road for up to 24 hours.
AB  - Five groups of 20 slaughter sheep of approximately 37.9 kg liveweight were
      transported by road for either three, nine, 15, 18 or 24 hours and three groups
      were not transported, one of them being deprived of food and water for 24 hours.
      Before and after transport the liveweight and various blood variables were
      measured and heart rate and behavioural observations were recorded from subsets
      of the animals. With increased journey time there was a decrease in liveweight
      and an increase in the plasma levels of free fatty acids, beta-hydroxybutyrate
      and urea; however, the changes over 24 hours were similar to those in the group
      deprived of food and water. In the transported sheep, the heart rate and levels
      of plasma cortisol and glucose were increased by the stresses of loading and the
      initial stages of the journey, but after nine hours the sheep appeared, to some
      extent, to have adapted. They were able to lie down and did not appear to be
      physically stressed. Measurements of plasma osmolality, total plasma protein and
      albumin did not indicate that the sheep had become severely dehydrated after 24
      hours of transport but upon their return, feeding and drinking activity was
      greater than that observed before the journey.

PMID- 7631479
TI  - Post mortem investigations on cetaceans found stranded on the coasts of Italy
      between 1990 and 1993.
AB  - Detailed pathological and virological examinations were carried out on 25
      cetaceans found stranded between 1990 and 1993 on the coasts of six Italian
      regions (Latium, Tuscany, Apulia, Abruzzo, Veneto and Sicily). There were 16
      striped dolphins (Stenella coeruleoalba), three bottlenosed dolphins (Tursiops
      truncatus), three Risso's dolphins (Grampus griseus), one rough-toothed dolphin
      (Steno bredanensis), one fin whale pup (Balaenoptera physalus), and one minke
      whale (Balaenoptera acutorostrata). Apart from parasitic diseases (44 per cent),
      the most frequently detected lesions were pneumonia (68 per cent), enteritis (44
      per cent), non-purulent hepatitis (40 per cent), interstitial nephritis (32 per
      cent) and encephalitis (32 per cent). Morbilivirus infection was diagnosed by
      immunocytochemistry in four striped dolphins, two stranded on the coasts of
      Latium in 1991 and two on the coasts of Tuscany in 1993. Despite the presence of
      lesions consistent with morbilliviral pneumonia in two other striped dolphins
      stranded on the coast of Apulia in 1991, no morbillivirus antigen was
      demonstrated in the tissues of these animals. Anticanine distemper virus
      antibodies were detected in the serum of the adult minke whale found stranded on
      the coast of Tuscany in 1993. However, no viruses were isolated from the tissues
      of any of the 25 cetaceans.

PMID- 7631480
TI  - A case of moxidectin failing to control ivermectin resistant Ostertagia species
      in goats.

PMID- 7631481
TI  - Feline spongiform encephalopathy in a cat in Norway.

PMID- 7631482
TI  - Dearth of locums, fees and veterinary manpower.

PMID- 7631483
TI  - Dearth of locums, fees and veterinary manpower.

PMID- 7631484
TI  - Identifying thoroughbreds.

PMID- 7631485
TI  - Priorities in animal care.

PMID- 7631486
TI  - Swan anaesthesia.

PMID- 7631487
TI  - In vivo non-invasive quantification of muscle damage following a single
      intramuscular injection of phenylbutazone in sheep.
AB  - Intramuscular drug administration can lead to more or less extensive muscle
      damage. The aim of the present study was to show the possibility of quantitating,
      in vivo and non-invasively, the equivalence of muscle destroyed by the
      administration of a test drug (phenylbutazone) known for its injurious
      properties. Creatine kinase (CK) kinetic parameters (clearance, volume of
      distribution) were measured in 6 sheep after an iv administration of muscle CK
      homogenate. In the same 6 sheep, CK release after iv and im 8 mg
      phenylbutazone/kg was measured. The calculated total CK released, based on the CK
      plasma clearance (0.28 mL/kg/min) and area under the curve of CK activity after
      im phenylbutazone administration was 191 +/- 140 U/kg. By relating this quantity
      to that of CK gluteal muscle (5114 +/- 891 U/g), it was calculated that im
      phenylbutazone administration was able to destroy an equivalence of 2.4 +/- 2.1 g
      of muscle. For the 2 main sites of im administration (neck and gluteal muscle),
      general equations are proposed to calculate the equivalence of muscle destroyed
      in sheep when only plasma CK activity following a test drug administration is
      available.

PMID- 7631488
TI  - The influence of heavy metal emissions and Fasciola hepatica infestation on the
      immunogenicity of a Listeria vaccine.
AB  - The effect of oral dosing with emissions containing heavy metals (mercury, lead,
      copper, cadmium, zinc and chromium) on immune status was tested in 3 groups of
      sheep. Two groups (Groups I and II) were given emissions for 15 d. One of these
      groups (Group I) was then also infested with Fasciola hepatica metacercaria on
      day 16. These 2 groups (Groups I and II) and a control group (Group C) were
      immunized with a Listeria vaccine on days 8 and 22. A decreased index of
      metabolic response (IMR) of phagocytes and reduced responses of lymphocytes to
      mitogenic activation with phytohemagglutinin and L monocytogenes antigen
      stimulation in the leukocyte migration-inhibition test were recorded. Decreased
      agglutination titers of serum antibodies against L monocytogenes were observed.
      The F hepatica infestation had no significant effect on the migration index or
      IMR.

PMID- 7631489
TI  - Effects of endosulfan and amitraz on feedlot performance, carcass yield and meat
      quality characteristics of Nubian goats.
AB  - The pesticides endosulfan and amitraz were fed to 2 groups of Nubian goats (3
      goats/group) at 5 mg/kg/d for 36 d to assess their effects on feedlot
      performance, carcass yield and meat quality. Growth rates, weight gains and feed
      conversion efficiencies were depressed insignificantly. The endosulfan-dosed
      group had significantly lower dressing-out percentage and both groups had
      significant depletions of omental and mesenteric fats. Significant reductions
      were also seen on body and cavity fats, the latter being severely reduced
      suggesting more mobilization of cavity fat than body fat. The fat-free body was
      homogenous with variations in the muscle/bone ratio reflected on carcass cuts.
      Meat quality was unaffected. Fat was the only chemical component of endosulfan
      dosed total lean significantly reduced. In all parameters the effects of
      endosulfan were more pronounced than those of amitraz.

PMID- 7631490
TI  - Induction of acute hypocalcemia in rats.
AB  - Decreased plasma calcium levels could produce important changes in cellular
      functions and drug responses. This communication describes the temporal decrease
      in calcemia that can be obtained in Sprague-Dawley rats after the ip
      administration of doses of 1 to 16 IU calcitonin. The injections caused
      significant reductions in calcemia in this strain of rats, but did not alter the
      behavior or general condition of the dosed animals. The method described permits
      the establishment of experimental models of hypocalcemic rats that will be very
      useful for physiological and pharmacological studies.

PMID- 7631492
TI  - Fumonisin B1 is fetotoxic in rats.
AB  - Groups of 5-6 pregnant F344/N rats were dosed (po) from d 8 to 12 of gestation
      with 30 or 60 mg purified fumonisin B1 (FB1)/kg body weight, or with a fat
      soluble extract of Fusarium proliferatum/corn culture derived from an amount of
      corn culture that would provide approximately 60 mg FB1/kg. Control rats were
      dosed with water or corn oil. Food intake was monitored daily during dosing.
      Fetal bone development was examined after staining with alizarin red, whereas
      internal organ development was examined in hematoxylin and eosin-stained tissue
      sections. Although group differences in maternal body weight were not
      statistically significant, weight was 6% less in dams dosed with 60 mg FB1/kg
      compared with the control group (p < 0.12). Relative litter weight was
      significantly suppressed by 60 mg FB1/kg. Ossification of the sternebrae and
      vertebral bodies was significantly impaired by FB1 treatment. Litters from
      mothers treated with a fat-soluble extract of F proliferatum/corn culture did not
      have suppression of weight or impairment of bone development. Fumonisin B1 is
      fetotoxic to rats by suppressing growth and fetal bone development.

PMID- 7631491
TI  - Clinical signs of ivermectin toxicity and the efficacy of antigabaergic
      convulsants as antidotes for ivermectin poisoning in epileptic chickens.
AB  - The clinical signs of ivermectin toxicity were determined in 6 groups of 10
      epileptic and 8 non-epileptic chickens for 72 h after dosing with sc injections
      of 5.0, 7.5, 10.0, 12.5 or 15.0 mg ivermectin/kg bw. At the 5.0 mg/kg dose, mild
      diarrhea developed 4 h post-dosing and lasted until the end of the 72-h
      monitoring period. With higher doses of ivermectin body weight, egg production
      and feed and water consumption were markedly reduced. Severe diarrhea, mydriasis,
      bradypnea, ataxia, sedation, coma and death occurred with the highest dose of
      ivermectin. No differences in the signs of ivermectin toxicity were observed
      between epileptic and non-epileptic chickens. To assess the efficacy of the
      antiGABAergic convulsants, methyl-beta carboline-carboxylate (beta-CCM),
      picrotoxin and pentylenetetrazol (PTZ), as antidotes for ivermectin toxicity, 8
      epileptic and 6 non-epileptic chickens/treatment group were given dosages of each
      convulsant which previously induced convulsions in 50% (ED50) and again in 100%
      (ED100) of treated chickens. These convulsants were given 6 h after dosing with
      15.0 mg ivermectin/kg. The ED100 dosages of picrotoxin and PTZ alleviated
      mydriasis and sedation, but did not reduce the diarrhea. The ED50 dose
      convulsants were not effective in reducing or alleviating ivermectin toxicity,
      nor was alleviation of any sign of ivermectin toxicity obtained with any dosage
      of beta-CCM. Although the dosages of these antiGABAergic convulsants used
      normally produced convulsions in epileptic and non-epileptic chickens, no
      convulsions were observed in chickens with ivermectin toxicity.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7631493
TI  - Gastrointestinal absorption of inorganic arsenic (V): The effect of concentration
      and interactions with phosphate and dichromate.
AB  - The absorption of inorganic pentavalent arsenic (As) by the rat small intestine
      was investigated using 2 different procedures: In vivo determination of overall
      extent of gastrointestinal absorption; and an intestinal perfusion technique. The
      aim was to determine the effect of concentration and the interaction with
      phosphate and dichromate anions on gastrointestinal absorption of As to
      understand the mechanism of As absorption at intestinal level. The results
      indicate there is a direct relationship, although not proportional, between the
      received dose and the absorbed amount of As. Intestinal absorption of As appears
      carried out by a saturable transport process. The phosphate produces a pronounced
      decrease in the intestinal absorption of As due to the fact that phosphate and As
      can share the same transport mechanism which is an active secondary carrier
      mediated system depending on Na+ and H+ gradient. Addition of dichromate to
      perfusion buffers significantly (p > 0.05) increased As absorption. Several
      hypothesis may explain this fact: Dichromate produces pH modifications at the
      intracellular level, providing an adequate H(+)-gradient for As absorption;
      dichromate exerts a caustic effect, which damages the intestinal wall at the
      microvilli level. This allows free diffusion of As through the resulting
      openings.

PMID- 7631494
TI  - Effects of the subchronic administration of zinc ethylene-bis-dithiocarbamate
      (zineb) to rabbits.
AB  - The effects of subchronic administration (90 d) of zineb were studied in male New
      Zealand White rabbits. Rabbits were allotted to 3 groups of 8 animals each and
      offered diets containing 0, 0.3 or 0.6% zineb. A marked decline in weight gain,
      hemoglobin concentration, hematocrit, and erythrocyte and leucocyte counts
      occurred at the highest zineb dosage. There was a dose-related depression in
      circulating thyroid hormones, whereas serum lipid concentration, particularly
      that of cholesterol and triglycerides, increased. Hepatic lipid concentration was
      considerably reduced in rabbits exposed to 0.6% zineb. Neither serum testosterone
      nor the activities of selected testicular enzymes showed changes suggestive of
      testicular involvement. Pathological changes were in agreement with biochemical
      findings; there was a marked dose-related enlargement of the thyroid showing
      histological colloid struma. An increase in relative weight and moderate
      glycogenosis were detected in liver, whereas no lesions occurred in testes. It
      was concluded that thyroid and liver are the main targets for zineb toxicity in
      the rabbit. Unlike the results from previous studies conducted on other food
      producing species, repeated exposure of rabbits to zineb failed to cause
      testicular damage. This might be related to the inability of zineb to
      significantly accumulate in the testes.

PMID- 7631495
TI  - Dichapetalum spp toxicity in cattle at a farm in Tanzania.
AB  - An investigation was carried out to establish the cause of mortalities during the
      dry season in cattle at a state livestock replacement farm at Kibaha in the Coast
      Region of Tanzania. Studies included a thorough review of the farm records,
      interviews with the farm staff, screening for parasites through examination of
      blood and lymph node smears, clinical examination of sick animals, and a survey
      of the grazing lands as well as postmortem examinations of the dead cattle.
      Circumstances incriminated plant poisoning as the cause of the deaths. A
      systematic survey of the pastures indicated a preponderance of Dichapetalum spp
      poisonous plants in areas in which most of the affected cattle had been grazing.
      Leaves of these plants were collected, dried, powdered and fed or drenched to 6
      goats and 24 wistar rats. Lesions in animals that died resembled those seen in
      dead cows--pulmonary congestion and edema, froth in the airways, hemorrhagic
      gastroenteritis, and variable quantities of serous effusions into serous
      cavities. Although Dichapetalum spp occur especially in coastal regions, previous
      cases of poisoning by this plant in Tanzania have not been published. This report
      documents a systematic toxicological trial to verify the poisonous potency of
      this plant.

PMID- 7631496
TI  - Renal failure is uncommon in Chinese patients with paracetamol (acetaminophen)
      poisoning.
AB  - The reported incidence of renal failure in unselected patients with paracetamol
      poisoning is about 1-2%. Since the introduction of antidotal therapy for
      paracetamol poisoning in 1973, renal failure is now mainly seen in those admitted
      too late for effective therapy and is usually associated with liver damage. To
      determine the incidence of renal failure in Chinese patients with paracetamol
      poisoning, a retrospective survey was conducted of 224 patients admitted to the
      Prince of Wales Hospital, Hong Kong, with paracetamol poisoning from January 1988
      to January 1994. Of the 28 patients at risk (plasma paracetamol concentrations
      above the recommended treatment line), 13 developed liver damage which was severe
      in 5. One patient with severe liver damage developed a transient increase in
      plasma creatinine concentration from 90 to 116 umol/L. All 28 patients completely
      recovered. Renal failure was uncommon in Chinese subjects (0.4%), and this was
      probably related to a lower incidence of liver damage which may be due to less
      chronic alcoholism as well as ethnic differences in paracetamol metabolism
      resulting in an inherent reduced susceptibility to its liver and renal toxicity.

PMID- 7631497
TI  - Anticholinergic poisoning due to Chinese herbal medicines.
AB  - Serious poisoning may occur following the consumption of Chinese herbal medicines
      (CHM) containing anticholinergics. The great majority of cases are probably
      related to the use of yangjinhua, the dried flower of Datura metel L, for
      treating bronchial asthma, chronic bronchitis, pains and flu symptoms. In some
      cases the use of CHM contaminated by atropine-like substances or fake herbs were
      suspected. Some ginseng (Panax ginseng) preparations might have been adulterated
      with Mandragora officinarum (scopolamine) and other herbs.

PMID- 7631498
TI  - The potential utility of animal poisoning data to identify human exposure to
      environmental toxins.
AB  - The database of the National Animal Poison Control Center (NAPCC) was evaluated
      as a source for animal poison data indicating human health hazards in indoor and
      outdoor environments. From 14,150 calls in the 1985 database, 259 cases were
      identified with histories suggesting human exposure. A subgroup of 25 cases with
      known human exposure was found. Dogs were the most common sentinel animal, but
      bird cases represented the highest proportional selection from the total 1985
      call list. Indoor exposures represented 43.2% of cases; the most common toxicants
      were insecticides, lead and toxic fumes. Exposures associated with lawns were
      mainly due to insecticides and herbicides and constituted 25.5% of cases. Other
      outdoor exposures composed the remaining 31.7% of cases, with insecticides,
      herbicides and unidentified toxins the leading categories. Many of the specific
      agents identified, such as organophosphate insecticides, lead, gas and fume
      toxins, and phenoxy herbicides are also risk factors in human diseases. This
      study indicates that databases such as NAPCC could serve as sources of sentinel
      animal intoxications for followup studies to evaluate known and potential human
      health hazards.

PMID- 7631499
TI  - Stray voltage and developmental, reproductive and other toxicology problems in
      dogs, cats and cows: a discussion.
AB  - Ten years ago, after 3 y of investigations, attempts to determine the cause(s) of
      reproductive and developmental problems at a dog kennel in Allegan County, MI
      were suspended. This kennel had lost more than 120 litters of Shetland Sheepdogs
      (Shelties) over the preceding 12 y; many of the puppies that died were deformed
      as were several that survived. Similar effects occurred in Persian cats, although
      on a smaller scale, and later in German Shepherds and Golden Retrievers. Such
      problems began after drilling a deeper water well and the building of a new
      kennel of concrete and metal fencing in 1969. Prior to that time the kennel owner
      had successfully bred and raised at least 15 litters/y of mostly Shelties in an
      old wooden chicken coop. Health problems in the kennel owner prevented her from
      breeding dogs in the late 1980's. She gradually resumed a more regular breeding
      schedule in 1989, initially with some success. However, in 1992 reproductive
      problems returned. Female dogs ceased cycling or had abnormal "unbreedable"
      seasons. Sperm checks revealed a lack of sperm in four males. Concurrently,
      neither the Persian nor mongrel female cats in the kennel showed signs of
      cycling. Two dairy farmers in Allegan County, who reportedly had similar health,
      reproductive and management concerns in cows, were contacted. Tests performed at
      these dairy farms had revealed the presence of what has commonly been called
      stray voltage. Equipment brought by the farmers to the kennel revealed the
      presence of AC and DC currents on the premises, which was later confirmed by a
      Staff Engineer of the Michigan Public Service Commission (PSC). Such current was
      detected even when the electrical power to the premises was shut off. For
      example, 2.45 volts AC and -0.150 volts DC were detected at the well head, with
      variable amounts detected at various locations in the kennel. The current was not
      constant, with transients (spikes) frequently detected. Similar problems were
      evident in Van Buren County at a recently constructed kennel about 15 miles south
      of the kennel in Allegan County. Shortly after moving to the property, health
      problems not previously experienced by the breeder began cropping up in the dogs.
      Experts from the power company, the PSC, and 2 independent consultants have taken
      a variety of measurements on the property. The tests confirmed the presence of
      stray voltage (AC and DC) with periodic voltage spikes, as well as
      electromagnetic fields and electric fields. None of the extensive tests have
      proven the property owner to be at fault.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7631500
TI  - Reversal of medetomidine sedation in sheep by atipamezole and yohimbine.
AB  - The antagonistic effect of the alpha 2-adrenoceptor antagonists atipamezole and
      yohimbine on medetomidine-induced sedation was studied in male Awassi sheep. The
      animals were sedated with an im injection of 40 micrograms medetomidine/kg bw.
      After recumbency, the sheep were injected iv with either 5 ml physiological
      saline solution (control), 0.2 mg atipamezole/kg or 0.2 mg yohimbine/kg. The
      saline-treated animals remained sedated and recumbent for 61.3 +/- 3.0 (mean +/-
      SE) min. Atipamezole or yohimbine significantly reduced the recumbency period to
      2.8 +/- 0.9 or 4.3 +/- 0.9 min, respectively. Atipamezole or yohimbine
      significantly increased the medetomidine-induced reductions in the heart rate,
      respiratory rate and ruminal contractions. Rectal temperature was neither
      affected by medetomidine nor by the subsequent administrations of antagonists.
      These data suggest the usefulness of atipamezole or yohimbine in antagonizing the
      sedative effects of medetomidine in sheep.

PMID- 7631501
TI  - Benzo[a]pyrene-induced alterations in total immune cell number and cell-surface
      antigen expression in the thymus, spleen and bone marrow of B6C3F1 mice.
AB  - Although considerable evidence suggests that carcinogenic polycyclic aromatic
      hydrocarbons are immunosuppressive compounds, limited information is available
      regarding precise effects of these agents on immune cells. In the present report,
      the effect of subchronic exposure to benzo[a]pyrene (B[a]P) on immune cells in
      bone marrow, thymus and spleen of B6C3F1 mice was investigated. B[a]P treatment
      was found to reduce thymic cellularity and also to significantly alter normal
      thymocyte differentiation, as indicated by expression of CD4 and CD8 cell-surface
      antigens. Exposure to B[a]P also reduced cellularity of the bone marrow,
      including decreased percentage and absolute number of CD45R+ B-lineage
      lymphocytes. Further, B[a]P treatment dramatically increased the percentage of
      CD44hi cells in bone marrow, while proportionately reducing CD44lo cells. These
      results may indicate CD44lo bone marrow cells, including prolymphocytic cells,
      represent sensitive targets of B[a]P. The spleens of treated mice were found
      deficient in both Thy 1.2+ T lymphocytes and CD45R+ B lymphocytes, effects that
      correlate well with the chemical-induced alterations observed in thymus and bone
      marrow, respectively.

PMID- 7631502
TI  - [A new zoonosis--investigation of Gardnerella vaginalis disease of fox. III.
      Epidemiological investigation].
AB  - By epidemiological investigation to Gardnerella vaginalis disease of fox of civil
      main farms raising foxes, this disease was showed to be susceptible to silver
      foxes, arctic foxes, red foxes and color foxes, the disease was mostly
      transmitted by copulation, infected foxes played the leading role in epidemic of
      the disease. Investigative results of all farms raising foxes showed infection
      rate of fox groups was 0.9-21.9%, resulting in abortion rate was 1.5-14.7%, empty
      rate was 3.2-47.5%. Serious harm was revealed to the disease. By serology and
      causative agent isolation, we had proved that the disease was able to infect
      feeder and manager, it belongs to zoonosis. Racoondog. mink and canine infect
      with the disease besides fox. White mouse, big white rat, gopher, guinea pig and
      rabbit for laboratory are not infected with the disease.

PMID- 7631503
TI  - [Over-expression of glutathione S-transferase in Streptomyces].
AB  - mRNA was isolated and purified from human liver, and it was also used as templet
      for cDNA synthesis under the existence of reverse transcriptase. Two primers were
      designed and synthesized according to GST gene sequence which has been reported,
      GST gene was obtained using cDNA as templet and PCR technique. The sequencing
      result indicated that the GST gene is reliable, it was subcloned into NdeI and
      Bg1 II sites of plasmid pIJ6021, and then introduced into Streptomyces lividans
      TK54. Proteins were isolated from transformants (TK54/pIJ4486 and TK54/pIJ6021)
      respectively, SDS-PAGE result showed that the GST over-expressed and its yield is
      about 15% in soluble proteins in Streptomyces.

PMID- 7631504
TI  - [A new subspecies of Streptomyces griseoflavus].
AB  - In the process of research of microorganism ecology on Dun Huang freseo a strain
      of Streptomyces culture No. 25706 was isolated. Its morphological cultural
      characteristics and physiological properties as well as antimicrobial spectrum
      were studied. It is near to Streptomyces griseoflavus as described in the
      literature, but there are some significant differences between the two strains.
      Therefore, it was considered, to be a new subspecies and named Streptomyces
      griseoflavus subsp. dunhuangensis n. subsp.

PMID- 7631505
TI  - [Geriatric pharmacology. Pharmacokinetics and pharmacodynamics in the elderly.
      Problems with geriatric and nootropic drugs].
AB  - The reasons for the increased frequency of adverse drug reactions in the elderly
      are a decrease in drug elimination, primarily via the kidneys, on the one hand
      and a decrease in adaptive counterregulatory mechanisms on the other hand that
      attenuate drug effects in younger subjects. Because of the decreased functional
      reserve in the aged drugs may adversely affect preexisting chronic diseases.
      Generally, the possibility that clinical symptoms in the elderly are drug-related
      has to be considered. Abrupt changes in dosage should be avoided. The indication
      of drug therapy should be reevaluated periodically. However, advanced age is no
      reason to withhold necessary medication. The compliance with or adherence to drug
      therapy may be improved by giving clear, written instructions, simplifying the
      dosage schedule and reducing the number of drugs, for instance by using
      combination drugs. Elderly patients are particularly vulnerable to the sedative
      effects of psychotropic drugs, resulting in cognitive impairment and motor
      incoordination with an increased risk of falls and hip fracture. There is no
      rational basis for the use of geriatric drugs that claim to stop or slow the
      aging process. Also the available evidence does not support the therapeutic value
      of so-called nootropic or cerebroactive drugs to improve mental function in the
      elderly.

PMID- 7631506
TI  - [Presentation of the international, emergency medicine relevant periodical
      spectrum and ethics and authorship and publication].
AB  - International scientific journals dealing with the broad subject of emergency
      medicine are listed. The following standards were applied: only journals from
      Europe or North America published in English or German were selected; whenever
      possible, the actual number of copies printed is mentioned; listing in the "Index
      Medicus" is stated; and, finally, the time course of the so-called "impact
      factor" from 1984 to 1992 is shown. The impact factor is a measure of how often
      the "average article" in a journal has been cited in a particular year. Basically
      it describes a ratio between actual citations and citable items published. It
      permits some qualification of quantitative data since it discounts the advantage
      of large journals over small journals and that of frequently published journals
      over less frequently issued ones. Journals from 12 different medical specialties
      have been selected for analysis: Emergency Medicine; Anesthesiology and Critical
      Care Medicine; Biomedical Engineering; Neurosciences; General Internal Medicine;
      Internal Medicine: Cardiology, Pulmonary Medicine, Infectious Diseases, and
      Public Health; Surgery; Pediatrics; Pharmacology; Physiology; Experimental
      Medicine. In addition, a few remarks are made dealing with ethics of publication
      and the increasing number of medical authors per article published. The terms
      "irresponsible authorship", "author inflation", "wasteful publication", and
      "abstract creep" are introduced and explained. Furthermore, strategies adopted
      from the literature to restrain those developments are introduced.

PMID- 7631507
TI  - [Cost effectiveness of misoprostol therapy in prevention of NSAID-induced stomach
      ulcers].
AB  - The efficacy of 400 micrograms misoprostol daily in the prevention of NSAID (non
      steroidal anti-inflammatory drug)-induced gastric ulcer has been proven. We
      calculated the cost-effectiveness of a 3-month course of treatment of 200
      micrograms twice daily for patients of the sick fund "Wiener
      Gebietskrankenkasse", based on charges of the year 1993. Since efficacy in
      preventing NSAID-induced gastric ulcers has not yet been proven for any other
      drug, we compared misoprostol-treated patients with untreated controls. The model
      was based on the following assumptions: 70% compliance with respect to
      misoprostol treatment, 5.6% incidence of gastric ulcer in patients protected with
      misoprostol, 21.7% incidence among unprotected NSAID users, 20% hospitalisation
      among patients with gastric ulcer. When using "Kassenpreis" (drug price paid by
      the sick funds) misoprostol treatment is cost-effective at costs of AS 64,100,-
      for inpatient care, upwards and at costs of AS 43,361,-upwards when using
      "Apothekeneinstandspreis" (drug price paid by pharmacies to wholesalers). In
      Austria costing system of inpatient care is based on a per diem fee. In 1993 the
      above costs corresponded to an average of 13 and 9 days, respectively, of
      inpatient care in Vienna. But costs of care increase by almost 25% per year and,
      hence, this conclusion is only temporarily valid and already in 1994 cost
      effectiveness will be reached in less days of inpatient care. Sensitivity
      analysis shows that cost-effectiveness mainly varies according to the incidence
      of gastric ulcer among unprotected adults, and the hospitalisation rate of
      gastric ulcer patients. Efficacy (gastric ulcer rate among misoprostol treated
      patients) and compliance have a relatively low impact.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7631508
TI  - [Arthur Biedl and the beginnings of modern endocrinology. On the 125th birthday
      of the Austrian pathophysiologist].
AB  - Modern endocrinology began to develop at the end of the nineteenth century in
      four stages: the recognition and localization of endocrine glands, the
      experimental proof of internal secretion by means of destruction and substitution
      in animals, their isolation and lastly the synthesis of pure hormones. Arthur
      Biedl (1869-1933), an assistant of Salomon Stricker (1834-1898), was essentially
      involved in the first two stages of this research process. This paper presents
      his work from 1895 to 1914.

PMID- 7631509
TI  - Induction of protective immunity in chickens orally immunized with inactivated
      infectious bursal disease virus.
AB  - The present studies were undertaken to examine the effects of oral administration
      of formalin-inactivated infectious bursal disease virus (IBDV) on the immune
      responses of chickens. Inactivated IBDV was suspended in phosphate-buffered
      saline containing sodium bicarbonate. This form of antigen, when administered by
      oral instillation, induced a serum antibody response against IBDV in chickens and
      these chickens were protected from subsequent viral challenge. The immunoglobulin
      class of IBDV-specific antibodies in serum was found to be IgG when determined by
      enzyme-linked immunosorbent assay. Cholera toxin, which has been reported to have
      potent mucosal adjuvant properties in mammals, did not enhance the serum antibody
      response. Oral followed by parenteral administrations of antigen induced an
      enhanced antibody response in chickens.

PMID- 7631510
TI  - Immune response of mice to immunization with subunit influenza A vaccine in DTP
      vaccine.
AB  - Experiments were carried out to examine the initial feasibility of immunizing
      infants and children with inactivated influenza virus vaccine combined with
      diphtheria-tetanus-pertussis (DTP) vaccine. Groups of mice were immunized with
      saline vaccine or vaccine mixed with DTP: three doses of vaccine were given 3
      weeks apart, and the antibody response and resistance to challenge infection were
      tested 3 weeks after the 1st and 3rd immunizations. The results showed that the
      antibody response and immunity to challenge virus infection were significantly
      greater for mice given vaccine in DTP than for mice given saline vaccine alone.
      Comparison of the response to graded doses of vaccine in saline or DTP indicated
      that vaccine in DTP was > 250-fold more effective in inducing serum antibody and
      protection than saline vaccine alone. The enhancing activity of DTP was
      significant for the alum component alone; however, most of the adjuvant effect
      was from the antigen components of the DTP vaccine. The results suggest that
      immunization against influenza in infants and young children could be achieved by
      combining small amounts of influenza antigen with DTP vaccines; however, the
      present results have been obtained in mice, and, since the responses to vaccines
      and adjuvants vary from species to species, the present results cannot be used to
      indicate similar results in human volunteers. The results indicate the potential
      value of an immunization procedure which should be tested in volunteers and which
      could provide a simple strategy for the immunization of at-risk infants and
      children against influenza.

PMID- 7631512
TI  - Evaluation of the polarographic technique for assay of the viability of freeze
      dried BCG vaccine: I. The polarographic technique.
AB  - In this paper, a new assay based on oxygen uptake assessed by polarography was
      evaluated with the aim of establishing the viability of freeze-dried BCG vaccine.
      An oxygen electrode possessing a temperature sensor was designed for this
      purpose. The polarographic method used had several advantages, particularly its
      rapidity and use of small amounts of biological material. These advantages are
      ideal for quality control of BCG vaccine.

PMID- 7631511
TI  - Adjuvanticity of ISCOMs incorporating a T cell-reactive lipoprotein of the
      facultative intracellular pathogen Francisella tularensis.
AB  - Immunostimulating complexes (ISCOMs) are known to be highly effective adjuvants
      for envelope antigens of viral agents, but have not been evaluated for use with
      antigens of intracellular bacteria. Balb/c mice were subcutaneously immunized
      with ISCOMs into which the T cell-reactive membrane protein TUL4 of Francisella
      tularensis had been incorporated. Spleen cells from the immunized mice responded
      in vitro to TUL4 and to heat-killed F. tularensis live vaccine strain (LVS) with
      proliferation and production of gamma-interferon, whereas spleen cells from
      control mice immunized with TUL4 only did not respond to the antigens. When mice
      immunized with TUL4 ISCOMs were challenged with F. tularensis LVS, bacterial
      counts in spleen and liver were lower than in non-immunized mice. Again, TUL4 had
      no effect when used without ISCOMs. When proteins of a total membrane preparation
      of F. tularensis LVS were incorporated in ISCOMs and used for immunization, a
      decrease in bacterial counts was obtained which was similar in magnitude to that
      of TUL4 ISCOMs. Generally, the adjuvant effects demonstrated did not compare with
      the excellent protective effect of live tularaemia vaccine. Nonetheless, ISCOMs
      provide a means whereby protective antigens of F. tularensis can be tested.

PMID- 7631513
TI  - Evaluation of the polarographic technique for assay of the viability of freeze
      dried BCG vaccine: II. Viability of the vaccine assessed by polarography, Warburg
      respirometry and colony counting.
AB  - A comparative study of the viability of 34 lots of freeze-dried BCG vaccine has
      been carried out using an oxygen electrode polarographic technique, Warburg
      respirometry and colony counting. There were no statistical differences between
      the results obtained with the polarographic and Warburg techniques. Both methods
      gave reliable and similar results and showed a positive correlation (r = 0.8615).
      Comparison between the polarographic and colony-counting methods showed a
      positive correlation (r = 0.6530); for comparison between the Warburg and colony
      counting methods, the correlation value was r = 0.6868. All the tests were
      significant at the level of alpha = 0.05. The advantages of the polarographic
      technique are that it is much less time- and material-consuming than other
      methods. It is a reliable, inexpensive and convenient method for BCG vaccine
      quality control.

PMID- 7631514
TI  - Comparison of Edmonston-Zagreb, Connaught and Schwarz measles vaccines in
      Cameroonian infants aged 3-8 months.
AB  - Eighty-five Cameroonian infants aged between 3 and 8 months were vaccinated with
      a high-dose Edmonston-Zagreb (EZ) strain (10(5.6) TDIC50), 81 with a low-dose
      Connaught strain (10(3) TCID50) and 74 with a medium-dose Schwarz strain (10(4)
      TCID50). Side-effects were mild (less than 32% of infants) and were not
      significantly different among the groups, nor were postvaccination anti-measles
      antibody levels. Postvaccination seropositivity and seroconversion rates were
      respectively 91.6% and 69% for EZ, 85.3% and 67.7% for Connaught and 75.6% and
      62.2% for Schwarz. In the light of concerns regarding high-titre measles
      vaccines, the overall performance of the Connaught strain warrants its wider
      evaluation in young infants.

PMID- 7631515
TI  - Weak immunogenicity of the preS2 sequence and lack of circumventing effect on the
      unresponsiveness to the hepatitis B virus vaccine.
AB  - The preS2 sequence is known to circumvent immunological unresponsiveness to the S
      protein and to induce a 'carrier' effect on the anti-S antibody production, in
      mice. In humans, an anti-S response was found in 100% and 97% of healthy subjects
      vaccinated with the S and S + preS2 preparations, respectively, whereas less than
      50% of drinkers responded whatever the vaccine used. Anti-preS2 were found in 44%
      of healthy recipients of the S + preS2 vaccine, whereas there were no anti-preS2
      responders in drinkers. Anti-preS2 remained undetectable in 32% of the blood
      donors hyperimmunized with the S + preS2 vaccine, whereas anti-S antibody boosted
      in all cases. In humans, in contrast to mice, immunogenicity of the preS2
      sequence appears weak and the preS sequence does not circumvent the anti-S
      unresponsiveness.

PMID- 7631516
TI  - Protection of macaques against simian immunodeficiency virus infection with
      inactivated vaccines: comparison of adjuvants, doses and challenge viruses. The
      European Concerted Action on 'Macaque Models for AIDS Research'.
AB  - Nine European laboratories contributed a total of 98 macaques towards a
      collaborative trial to study the ability of formaldehyde-inactivated or subunit
      SIV vaccines to protect immunized animals against live virus challenges. Four
      adjuvants, three dose levels and two immunization schedules were compared. Fifty
      two of 61 (85%) immunized animals were protected against infection after
      challenge with either homologous or heterologous virus strains grown in human
      cells. Optimum protection required a high dose of antigen and a prolonged
      immunization schedule. On the day of challenge the titres of antibodies to SIV
      and to host cell components, as well as the titres of neutralizing antibodies,
      were significantly higher in the protected animals than in the non-protected.
      Forty-four vaccinated macaques (of which 36 were protected against previous
      challenges grown in human cells) and 28 naive animals were then challenged with
      extracellular or cell-associated SIV grown in simian cells. All naive animals and
      all vaccinees challenged with extracellular SIV became infected. Four of the
      eight animals challenged with cell-associated viruses were protected. These
      results clearly indicate that vaccines which potently protect against SIV grown
      in human cells, do not protect against SIV grown in simian cells. The cell
      substrate on which challenge viruses are grown is clearly significant in
      interpreting the results of vaccine trials. This trial has demonstrated that SIV
      vaccines using different adjuvants can protect macaques against SIV grown in
      human cells but not against extracellular SIV grown in simian cells. These
      results have important relevance to the development of HIV vaccines for
      humans.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7631517
TI  - The Brucella abortus RB51 vaccine does not confer protection against Brucella
      ovis in rams.
AB  - The protective efficacy against Brucella ovis of the live vaccine Brucella
      abortus strain RB51 has been evaluated in rams using the attenuated B. melitensis
      strain Rev 1 as a reference vaccine. Sixteen Brucella-free rams, 6 months of age,
      were vaccinated subcutaneously with 4.18 x 10(10) c.f.u. RB51. Sixteen rams of
      the same condition and age were vaccinated subcutaneously the same day with 1.1 x
      10(9) c.f.u. Rev 1. Fifteen similar rams were kept unvaccinated as controls. Six
      months after vaccination all rams were challenged with 3 x 10(9) c.f.u. B. ovis
      and slaughtered 8 weeks thereafter for bacteriological and pathological studies.
      The percentage of rams that were found infected was 68% (Rev 1), 100% (RB51) and
      100% (controls). At necropsy, the percentage of organs found to be infected was
      significantly lower (p < 0.0005) in Rev 1-vaccinated (34%) than in RB51
      vaccinated rams (74%) or controls (69%). In conclusion, the RB51 vaccine did not
      confer protective immunity against B. ovis in rams.

PMID- 7631518
TI  - Bases for the early immune response after rechallenge or component vaccination in
      an animal model of acute Mycoplasma pneumoniae pneumonitis.
AB  - The pathology of Mycoplasma pneumoniae pulmonary infection for a hamster model
      was examined after whole bacterium rechallenge or component vaccination. Animals
      which, after an initial infection, were rechallenged with either live or heat
      killed M. pneumoniae inocula developed severe early recall lesions in the first 3
      days. In contrast, animals infected once develop maximum histopathology at
      approximately 10-14 days. A severe perivascular inflammatory cellular infiltrate
      developed in the rechallenged groups, and pulmonary pathology could also be
      elicited by rechallenge with bacterial growth medium components. Component
      vaccination with protein P1 did not reduce disease in comparison to once-infected
      controls, and vaccination promoted an early immune recall response as well. We
      conclude that an early immune response needs to be sought in all future
      experiments of challenge/rechallenge or vaccination. Vaccine studies will require
      an understanding of both protective and harmful immunogens.

PMID- 7631519
TI  - Improved immunogenicity of oral D x RRV reassortant rotavirus vaccine by
      Lactobacillus casei GG.
AB  - In a search for new strategies to improve oral vaccination, the effect of orally
      administered Lactobacillus casei strain GG (LGG) in conjunction with D x RRV
      rhesus-human reassortant live oral rotavirus vaccine was tested in 2-5-month-old
      infants. Infants who received LGG showed an increased response with regard to
      rotavirus-specific IgM secreting cells, measured using an ELISPOT technique, on
      day 8 after vaccination. In infants receiving LGG or placebo, respectively, a
      rotavirus IgM seroconversion was detected in 26/27 (96%), versus 23/27 (85%)
      cases (p = 0.15) and rotavirus IgA seroconversion was detected in 26/28 (93%)
      versus 20/27 (74%) cases (p = 0.05). These findings suggest that LGG has an
      immunostimulating effect on oral rotavirus vaccination. The clinical significance
      of LGG-enhanced immune responses to oral vaccines should be further evaluated.

PMID- 7631520
TI  - In vivo CTL induction with point-substituted ovalbumin peptides: immunogenicity
      correlates with peptide-induced MHC class I stability.
AB  - Class I molecules are conformationally sensitive to peptide binding, prolonging
      the complex's half-life on the surface of the cell. By making a series of H2-Kb
      anchor motif amino acid point substitutions in the ovalbumin 257-264 octamer, we
      were able to analyse subtle changes in peptide binding, Kb stabilization and in
      vivo immunogenicity. The cell line RMA-S was used to determine peptide-dependent
      Kb stabilization under equilibrium and non-equilibrium binding conditions.
      Sixteen conservative and non-conservative amino acid substitutions were made at
      positions 3, 5 or 8 of the peptide. At 37 degrees C, Kb stabilization was
      differentially affected by these substitutions, with several substitutions
      severely affecting Kb surface expression. When the substituted peptides were used
      as immunogens to prime cytotoxic T lymphocytes (CTL) in vivo, each peptide's
      ability to stabilize Kb directly correlated with the intensity of specific CTL
      activation. We conclude that peptide class I stabilization is an important
      influencing factor in determining cell surface steady-state expression of these
      peptides and thus the breadth of CTL recruitment. These concepts may relate the
      phenomenon of immunodominance to cell surface-presented peptide steady-state
      levels and may also aid in peptide vaccine design.

PMID- 7631521
TI  - Neutralizing antibodies against highly cytopathic Zairian human immunodeficiency
      type-1 virus (HIV-1) NDK are present in sera outside Africa.
AB  - The prototype virus HIV-1 LAV and highly cytopathic Zairian virus HIV-1 NDK
      belong to the genetic subtypes B and D and represent low and highly cytopathic
      phenotypes, respectively. Their neutralization pattern and serotype were studied
      with respect to differences in their genotypes and phenotypes. Sera from HIV-1
      infected persons living in four geographically distant areas, Philadelphia (USA),
      Ribeirao Preto (Brazil), Marseille (France) and Kinshasa (Zaire), were tested for
      the presence of type-specific and group-specific cross-reacting neutralizing
      antibodies against HIV-1 LAV and HIV-1 NDK in a continuous cell line MT4. The
      majority of type-specific antibodies were directed against HIV-1 LAV in
      Philadelphia, Ribeirao Preto and Marseille, and against HIV-1 NDK in Kinshasa.
      However, some sera with an HIV-1 NDK type-specific neutralization pattern were
      also found in Philadelphia, Ribeirao Preto and Marseille. These results indicate
      that strains with an HIV-1 NDK-like serotype could be found outside Africa. The
      presence of type-specific neutralizing antibodies against HIV-1 NDK in sera from
      North and South America and Europe should be taken into account during attempts
      to serotype HIV as well as in the course of selection of HIV-1 candidate strains
      for an AIDS vaccine.

PMID- 7631522
TI  - [A taxonomic interpretation of the morphological variability exemplified by
      common voles (Microtus s. lato, Rodentia)].
AB  - An analysis of variability of the crown pattern of the first lower molars in gray
      voles has indicated the existence of two trends in its transformation, the
      "pitimoid" and the "ratticepoid" ones. The first trend is characteristic of
      Microtus, whereas the second one is found in Alexandromys. These taxa differ also
      by diploid chromosome numbers. This regular pattern of variability is discussed
      from the taxonomic standpoint.

PMID- 7631523
TI  - [The means for the morphofunctional transformations of hematophagous insects].
AB  - Morphofunctional transformations of hematophagous insects, connected with forming
      the type of parasitism is performed by different forms of adaptation morphosis.
      Most morphological changes occur within the framework of idioadaptations
      (allomorphoses); which is especially characteristic of all free-living
      hematophagous groups. The transition of hematophagues to ectoparasitism,
      especially permanent, is accompanied, besides idioadaptations, by cenogenetic
      shifts (pupigenous dipterans, hemipterans), as well as by processes of
      degradation of organs, with a generally hypomorphous development of a group
      (lice). The degree of reduction of aromorphous characters reflects the level of
      morphological and ecological specialization of hematophages.

PMID- 7631524
TI  - [A review of the suspension of paired limbs in vertebrates from functional
      viewpoints].
AB  - The functional interpretation is delivered of the principal morphological
      subdivisions of the paired limbs in the vertebrate animals, that is of the
      girdles and free parts. To distinguish between those, the functional criteria are
      suggested. On this basis the variants are considered of suspension of the fore
      and hind limbs in various groups of Gnathostomata. In the hind limbs the boundary
      between the girdle and the free part does always pass through the hip joint. In
      the fore limb the corresponding boundary passes through the shoulder joint in
      fishes. However, in most tetrapods it shifts proximally due to the release of the
      scapulocoracoid mobility. This tendency reached its maximum in turtles and
      viviparous mammals. The main attention is paid to the analysis of the arrangement
      of the scapulocoracoid suspension in various groups of tetrapods.

PMID- 7631526
TI  - [Vascular Surgery. Joint annual meeting of the Vascular Surgery Associations of
      Germany, Austria, and Switzerland. Salzburg, 25-27 May 1995. Abstract].

PMID- 7631525
TI  - [Natural amino acids as effective stimuli evoking chemoreceptor-directed behavior
      in anuran tadpoles].
AB  - The behavioral reactions of tadpoles of four anuran species, inhabiting Moscow
      Region (Rana temporaria L., R. lessonae Cam., Bufo bufo, and Pelobates fuscus
      Laur.), on solutions of natural L-amino-acids of different concentrations. It was
      shown that none of the tadpoles respond to solutions of most amino-acids with
      concentrations less than 10(-2) mole/l. Sequences of relative efficiency of amino
      acids as chemical stimuli, inducing feeding behaviour. The sequences display
      interspecific differences, however, positively correlate in different amino-acid
      content during pairwise comparison of species. For tadpoles of later
      developmental stages asparagine, glutamine, and lysine are good feeding behavior
      stimuli; proline is little or not effective. A reaction of avoidance of arginine,
      more pronounced in earlier developmental stages was observed in Bufo bufo
      tadpoles. The sensitivity of different age tadpoles to alanine, valine,
      glutamine, lysine, ornithine, and proline was studied by registering behavioral
      responses at different developmental stages. At earlier stages sensitivity is
      rather high (up to 10(-4) mole/l in R. temporaria tadpoles), and subsequently
      decreases in ontogenesis to an average level of 10(-4) mole/l. Tadpoles of
      different species, but similar developmental stages were found to differ in their
      sensitivity to amino-acids. Experiments with olfactory deprivation of P. fuscus
      tadpoles showed amino-acid sensitivity to be connected with olfaction, whereas
      behavioral responses to amino-acid solutions with concentrations 10(-2) mole/l
      may be connected with any exterochemoreception system.

PMID- 7631527
TI  - Heat-shock proteins in medicine.

PMID- 7631529
TI  - Precore mutant chronic hepatitis B in an autochthonous Belgian population: a
      study of ten patients.
AB  - The mode of contamination, presentation, clinical evolution and liver histology
      of 10 native Belgian patients with chronic hepatitis B likely due to a peculiar
      viral strain, the so called precore mutant hepatitis B virus were reviewed. This
      viral strain first described in Southern European regions is characterized by a
      mutation of a single base change at nucleotide 1896 in the preterminal codon of
      the precore region which creates a stop codon that prevents the production of
      HBeAg. In this setting, abnormal liver biochemistry and active viral replication
      as evidenced by HBV DNA positivity often coincides with a serological profile
      similar to that observed in healthy HBsAg carriers. Our data indicate that
      chronic hepatitis related to such a viral strain may be observed in a native
      Belgian population. This unusual presentation of chronic hepatitis B should thus
      be kept in mind when interpreting atypical sero-biochemical features, evaluating
      the risk of infectivity and the potential benefit of antiviral therapy.

PMID- 7631528
TI  - Mediastinal B-cell lymphoma with sclerosis: clinical features and treatment
      results in 10 patients.
AB  - Mediastinal large-B-cell lymphoma with sclerosis is now considered to be a
      discrete subtype of lymphoma. It probably originates in the thymus, a T-cell
      organ. Early publications consider this lymphoma as an aggressive disorder with
      poor prognosis. We studied retrospectively ten consecutive patients with
      mediastinal B-cell lymphoma with sclerosis seen in the department of hematology.
      Nine were women. The median age at diagnosis was 38.3 years (16-60). Dyspnea
      (experienced by 7 patients), chest pain (5) and cough (10) were the most common
      clinical features at presentation. Superior vena cava syndrome occurred in three
      patients. Five had infiltration of the chest wall or of the pulmonary tissue.
      Four patients were in clinical stage I (all bulky > 10 cm), four in stage IIE,
      one was in stage IIE and one in stage IV (Ann Arbor classification). All patients
      were treated with intensive chemotherapy, mostly containing cyclophosphamide,
      doxorubicin, vincristine or vindesine, bleomycin and prednisone, combined with
      etoposide or teniposide and methotrexate. Nine patients responded well to
      chemotherapy (tumor reduction > 75%). One patient progressed. Eight patients
      received involved field radiotherapy (36-40 Gy) after chemotherapy. The two other
      patients were treated with intensive chemotherapy (BEAC, BCNU, etoposide,
      cytarabine, cyclophosphamide), followed by autologous bone marrow
      transplantation. Two patients died: one patient received autologous bone marrow
      transplantation in partial remission and relapsed after 6 months; the other
      patient had progressive disease despite chemotherapy, surgery and radiotherapy.
      Mean follow-up is 54.6 months (15-118) with 8 patients still remaining in
      complete remission. In patients with mediastinal B-cell lymphoma, tumour
      localisation is often limited to the thorax.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7631530
TI  - Long-term oxygen therapy with concentrators and liquid oxygen.
AB  - The National Institute for Insurance of Disease and Disablement (RIZIV/INAMI) in
      Belgium reimburses the costs of long term oxygen therapy (LTOT) by concentrators
      since 1984 and by liquid oxygen since 1988 for specific categories of patients
      supervised by approved medical centers. Since then we prescribed these therapies
      for 83 patients (49 with COPD, 12 with lung fibrosis, 22 with miscellaneous
      diseases). Since 1984 40 concentrators were prescribed of which 34 have been
      installed and 11 were still operating in July 1992 at the end of the study: 12
      patients died, 2 stopped LTOT and 10 switched to liquid oxygen. Since 1989 43
      patients started with liquid oxygen systems, together with the 10 patients who
      switched from concentrators to liquid oxygen, thus 53 liquid oxygen systems had
      been described and 46 were still in use in July 1992: 5 patients died and 2
      stopped LTOT. Patient characteristics at entry were: age 62 +/- 11 years (mean +/
      1SD), PaO2 50 +/- 6 mmHg, PaCO2 47 +/- 10 mmHg, polycythemia in 12%, clinical
      right heart failure in 47% and ECG signs of right ventricle hypertrophy in 70%.
      Two year survival was 75% for the whole group and 60% for the COPD patients. In
      patients with COPD improvement of PaO2 (on air) after 1 year of LTOT (+ 10 +/- 8
      mmHg in survivors versus 0 +/- 6 mmHg in non-survivors) was significantly related
      to survival (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7631531
TI  - [Chest pain and electrocardiographic changes in the presence of stenosis of the
      left common coronary artery].
AB  - Twelve-lead electrocardiogram were studied in 40 consecutive patients with
      angiographic left main coronary artery disease. The ECG were analysed during
      chest pain. The most frequent pattern was a ST elevation (> 0.1 mV) in lead a VR
      alone or with ST depression (> 0.2 mV) in the anterior or lateral leads. In
      coronary artery disease patients, the 12-lead electrocardiogram at rest remains
      the best test to detect patients at higher risk for massive myocardial infarction
      or death.

PMID- 7631532
TI  - [Pituitary apoplexy of a gonadotrophinoma and TRH/GnRH tests. Literature review].
AB  - Pituitary apoplexy is a rare but sometimes dramatic complication of pituitary
      tumors. We report the case of a 64-year-old man with a macroadenoma who
      complained of a sudden and intense headache after a dynamic TRH (200 micrograms)
      and GnRH (100 micrograms) test. Two days later, he presented an acute
      ophthalmoplegia with fever and deteriorating consciousness. Emergency CT scan
      showed contrast hypofixation compatible with necrosis of the adenoma. Surgical,
      tumoral decompression resolved quickly almost all symptoms. Immunohistochemical
      study of the tumor confirmed the diagnosis of gonadotropinoma. Several similar
      cases of pituitary apoplexy occurring after TRH or GnRH tests have been described
      the last ten years. As this test may sometimes confirm the diagnosis of
      gonadotropinoma, it should be performed with caution in cases of clinically non
      functioning pituitary macroadenoma.

PMID- 7631533
TI  - HIV-1 group O infection in Belgium.

PMID- 7631534
TI  - Cervical smears prepared by an automated device versus the conventional method. A
      comparative analysis.
AB  - An automated, fluid-based method for the preparation of cervical Papanicolaou
      smears/slides was compared to the conventional Papanicolaou smear (CPS) method
      used for the screening of neoplasia. We determined diagnostic agreement and
      sources of error for diagnostic disagreement. For 665 patients, one cervical
      sample was collected to make one CPS. The collection devices, a wooden Ayre
      spatula and endocervical brush, were rinsed into a vial with fluid medium to be
      processed in the automated device. All slides were distributed among five
      cytotechnologists in a blind fashion. Exact diagnostic agreement was 94.6%. The
      results were not statistically significant (P > or = .70, McNemar's test) but
      were clinically important, as evidenced by the detection of low grade lesions
      (LGL), during initial screening, on three slides prepared by the automated device
      but not on their matched-pair CPSs (0.5% of all specimens). After reevaluation,
      the three matched CPSs demonstrated LGL. Sources of diagnostic error on the CPSs
      were: air-drying artifact, obscuring blood/inflammation, crowding/overlapping of
      cells and/or absence of diagnostic cells. The only source of error in the
      automated-method smears was absence of diagnostic cells.

PMID- 7631535
TI  - Comparison of ThinPrep preparations with conventional cervicovaginal smears.
      Practical considerations.
AB  - This study compared cytologic quality, diagnostic accuracy, detection of
      endocervical and endometrial cells and yeast, screening times and costs for 128
      ThinPrep preparations (TP) to the corresponding conventional cervicovaginal
      cytologic smears (CCVS). Final diagnoses agreed in 114 (89%) cases. There were
      four discrepancies between atypical squamous cells of undetermined significance
      and low grade squamous intraepithelial lesion. The number of abnormal cells was
      lower in TP than in CCVS. Endocervical and endometrial cells were detected less
      frequently in TP than in CCVS. Yeast forms were seen rarely but were identified
      in both CCVS and TP. Inflammation and blood were less prominent on TP. While some
      CCVS showed artifacts related to fixation, cell preservation was optimal in all
      TP. Screening times were significantly shorter for TP than for CCVS. The combined
      cost of reagents, preparation and screening for an average TP was $1.78 higher
      than for a CCVS. We conclude that the use of TP for cervicovaginal smears reduces
      screening time and produces better cytologic preparations. However, cost-benefit
      analyses, readjustments in criteria for diagnosis of dysplasia and improvements
      in the recovery of glandular cells may be necessary before this method is used
      instead of CCVS.

PMID- 7631536
TI  - Adenomyomatous, lower uterine segment and endocervical polyps in cervicovaginal
      smears.
AB  - To the best of our knowledge, the specific features of polyps in cervicovaginal
      smears have not been described; that fact prompted us to undertake this study.
      Fifty-seven cases of polyps below the uterine fundus with cytohistopathologic
      correlations were analyzed. The tissue diagnoses were 2 cases of adenomyomatous,
      2 cases of lower uterine and 53 cases of endocervical polyps. In the
      cervicovaginal smears, adenomyomatous polyps presented as cohesive fragments with
      frayed edges, revealing spindle cells with bipolar cytoplasmic processes. Lower
      uterine segment polyps showed peculiar tissue fragments composed of several
      fractured arterioles connected by sheets of small stromal cells. Endocervical
      polyps presented as smooth-bordered, polypoid tissue fragments, lined at the
      outermost layer with simple columnar cells, sandwiched within a pale intermediate
      zone and packed at their inner core with numerous small, dark stromal cells. This
      specific finding, however, was observed in only one case. The remaining 52
      patients had no specific findings in their smears.

PMID- 7631537
TI  - Discordance between cytologic and histologic reports in cervical intraepithelial
      neoplasia. Results of a one-year audit.
AB  - In order to investigate the factors contributing to cases in which the cytology
      and histology reports of cervical intraepithelial neoplasia (CIN) differ, we
      assessed the impact of careful review of the biopsy and its corresponding
      cervical smear. In a one-year audit of all cervical biopsies we found that 18.8%
      of biopsy-smear pairs disagreed by at least two grades of CIN. Following review
      the mismatch rate fell by 47%, mainly due to a drop in the number of cases in
      which the smear showed less severe CIN than did the biopsy. The proportion of
      cases in which the cytologic impression of CIN was greater than the histologic
      was changed little. The fall in the mismatch rate was seen after review of the
      smears, while a similar review of the histology did not alter the rate of
      mismatch. Neither the presence of koilocytotic changes on either cytology,
      histology or both, nor the size of the biopsy (punch vs. cone/hysterectomy)
      influenced the occurrence of such discrepancies. A similar review of the smears
      and biopsies of matching cases of CIN revealed no significant changes. This
      suggests particular difficulties of interpretation in the mismatching cases. In
      those cases with persistent mismatch an additional element of sampling error must
      be assumed to be the main cause even though all smears were considered of
      adequate quality.

PMID- 7631539
TI  - Cytologic observations preceding high grade squamous intraepithelial lesions.
AB  - There is some evidence that a significant proportion (12%) of women,
      prospectively followed after negative cervical cytologic findings, develop tissue
      proven high grade squamous intraepithelial neoplasia (HSIL) within a short period
      (up to 24 months). The present study was undertaken to address the validity of
      this statement since such a high prevalence of spontaneous HSIL, if true, may
      challenge the value of an annual cervicovaginal cytologic smear examination.
      Cytologic smears collected from 82 patients with tissue-proven HSIL and obtained
      in the preceding 24 months were evaluated. The vast majority (90%) of these
      smears revealed evidence of cervical epithelial abnormalities prior to the
      development of HSIL-88% at 24 months and 96% at 12 months. The cytomorphologic
      features of low grade squamous intraepithelial neoplasia were observed in 45% of
      the smears, while the remaining cases were not normal or negative but had
      cytologic evidence of human papillomavirus (HPV)-associated changes (described
      elsewhere), including binucleation and multinucleation, epithelial plaques and
      pearl formations, and hyperkeratosis, dyskeratosis and parakeratosis. Persistent
      negative cytology was found in only three cases. Although these HPV-related
      cellular changes may not have an independent predictive value for HSIL, our study
      demonstrated that their awareness and detection can help to identify women at
      risk of potentially more advanced lesions. Thus, an annual cytologic smear
      examination is valuable and accurately reflects the presence of HPV-associated
      epithelial changes and precursor lesions of HSIL.

PMID- 7631538
TI  - Polymerase chain reaction. A sensitive indicator of the prevalence of human
      papillomavirus DNA in a population with sexually transmitted disease.
AB  - A total of 311 cervical samples from first attenders at a sexually transmitted
      disease clinic assayed for human papillomavirus (HPV) DNA with ViraType (VT) were
      analyzed with the polymerase chain reaction (PCR) for HPV using HPV L1 consensus
      primers and typed using L1 type-specific probes for 6/11, 16, 18 and 33. The
      prevalence of HPV by PCR was almost double that by VT (23.5% as compared to
      12.6%, respectively). The increase was due largely to HPV types other than 6/11,
      16, 18 and 33 (61.8%), while HPV types 6/11, 16 and 18 were responsible for 5.9%,
      2.9% and 11.8%, respectively. Equal numbers of mixed infections of HPV 6/11/18
      and HPV 16/18 each contributed to 8.8%. Mixed infection, as determined by VT, was
      11% and increased to 40% with PCR. While the increase in the HPV detection rate
      by PCR was evident in all clinical categories examined (patients with no warts
      evident and no past history of warts, with no warts but a past history of warts
      and with clinical condylomata), a statistically significant increase occurred
      only in the first group, reflecting the increased sensitivity of PCR in detecting
      latent infection.

PMID- 7631540
TI  - Evaluation of estradiol in aspirated ovarian cystic lesions.
AB  - During a three-year period, 217 ovarian cystic lesions were evaluated by both
      fine needle aspiration (FNA) cytology and estradiol (E2) assay at Royal Women's
      Hospital. One hundred three ovarian lesions were subsequently subjected to
      histologic examination, and 79 cyst fluids were assayed for progesterone. Of the
      151 cystic lesions diagnosed by cytology/histology, 50 were follicular cysts, and
      90% had E2 content > 20 nmol/L. The remaining 101 nonfollicular cystic lesions
      represented a heterogeneous group, but 99% had E2 content < 20 nmol/L. The
      sensitivity of E2 content > 20 nmol/L for follicular cysts was 90% and the
      specificity 99%. In contrast, progesterone was elevated in follicular cyst fluid
      but also in many other types of cysts. Consideration of E2 content in the 66
      cysts undiagnosed by histology/cytology revealed 33 follicular cysts. The precise
      nature of the 33 nonfollicular cystic lesions remains unknown, and further
      investigations, including surgery, are warranted. It is concluded that E2 assay,
      unlike progesterone assay, constitutes a useful ancillary diagnostic clue in the
      evaluation of ovarian cystic lesions in the premenopausal woman.

PMID- 7631541
TI  - Transformation of follicular lymphoma. Expression of p53 and bcl-2 oncoprotein,
      apoptosis and cell proliferation.
AB  - Transformation in follicular lymphoma represents an abrupt transition in tumor
      biology. The protein product of the bcl-2 oncogene is overexpressed in most
      follicular lymphomas and inhibits apoptosis. The protein product of the p53
      oncogene prevents cell proliferation and induces apoptosis and is overexpressed
      in the dysfunctional (mutated) form. We studied 15 transformed lymphomas (large
      cell type), 7 follicular lymphomas before transformation and 2 control groups of
      follicular center cell lymphomas with no evidence of transformation (9 small
      cleaved cell and 10 de novo large cell lymphomas). High p53 expression (> or =
      45% cells) was detected by immunostaining in 9/15 transformed lymphomas as
      compared with 0/10 de novo large cell lymphomas and 1/7 follicular lymphomas.
      Overexpression of bcl-2 (> or = 50% cells) was similar in transformed (11/15) and
      de novo large cell lymphomas (6/10). The apoptotic index was high (> or = 2%) in
      all transformed and large cell lymphomas and low in all follicular lymphomas and
      in the control group of small cleaved cell lymphomas. The apoptotic index in the
      transformed lymphomas appeared to be independent of bcl-2 expression and was
      sometimes paradoxically high in the presence of both p53 and bcl-2
      overexpression. The apoptotic index was weakly associated with bcl-2 expression
      in de novo large cell lymphomas. Expression of p53 did not correlate with
      proliferation index. Our results indicate that p53 overexpression is a specific
      step associated with transformation and may occur shortly before it. This is not
      seen in de novo large cell lymphoma. Furthermore, the high apoptotic index in
      transformed lymphomas often occurs despite overexpression of bcl-2 and p53,
      implying that other factors may induce apoptosis in these tumors.

PMID- 7631544
TI  - Fine needle aspiration cytology of extramedullary chronic myelogenous leukemia.
AB  - Chronic myelogenous leukemia (CML) shows extramedullary involvement in 10% of
      cases. We report the cytologic findings of fine needle aspiration (FNA) of
      recurrent CML in extramedullary sites in 11 patients with CML. The patients' ages
      ranged from 24 to 62 years (median, 38 years). There were seven male and four
      female patients. The aspiration sites were mostly lymph nodes (cervical in 7,
      retroperitoneal in 2, axillary in 1) and abdominal wall soft tissue (1). The
      numbers of blasts in the aspirates ranged from 27% to over 90%. Confirmation of
      the myeloid nature of the blasts was done using naphthol AS-D chloroacetate
      esterase in one case. Cytologic and flow cytometric immunotyping was done in
      eight cases. Two cases were based on cytomorphologic features only. Two of the
      eight immunophenotyped aspirates showed evidence of T-lymphoblastic
      differentiation. Another showed a mixed myeloid and T-cell phenotype. Blasts were
      seen in the peripheral blood and bone marrow in 4 of the 11 patients. We thus
      conclude that extramedullary involvement by CML in our series was associated with
      younger age, high incidence of cervical lymphadenopathy, increased blasts and
      frequent lack of bone marrow and peripheral blood involvement. T-cell phenotypes
      appeared to be higher in our series than reported in the literature. This
      suggests that there is a need for phenotyping some aspirates of recurrent
      extramedullary CML, mainly to evaluate the possibility of dedifferentiation and
      its possible impact on the behavior of the neoplasm.

PMID- 7631542
TI  - Effects of hormone replacement therapy on fine needle aspiration cytology of the
      breast.
AB  - To investigate the possibility that hormone replacement therapy (HRT) might
      induce morphologic changes in breast cytology simulating malignancy, we
      determined the subjective interpretation and objective morphometric features of
      39 fine needle aspiration cytology samples from women who were using a variety of
      HRT preparations. Cases were matched for age and final diagnosis (assessed by a
      triple approach) with women who had never used HRT. Cytocentrifuge preparations
      stained with Papanicolaou stain were assessed by two observers for cellularity
      and diagnosis. Although diagnostic accuracy was slightly higher in HRT than non
      HRT samples, there was no significant difference in the assessments of
      cellularity and diagnosis between the two observers or between HRT and non-HRT
      samples. Nuclear areas in HRT samples were larger than in non-HRT samples,
      measured using computerized image morphometry; this difference did not induce the
      observer to diagnose malignancy more frequently. HRT had no adverse effect upon
      the accuracy of interpreting breast fine needle aspiration cytology samples.

PMID- 7631543
TI  - Pleural effusions in human immunodeficiency virus-infected patients. Correlation
      with concomitant pulmonary diseases.
AB  - The objective of our study was to evaluate the prevalence of pleural effusions in
      patients with the acquired immunodeficiency syndrome, to correlate these
      effusions with any concomitant pulmonary diseases and to evaluate the role of
      cytologic examination in the diagnosis of the effusions. Twenty-eight of 389
      (7.2%) human immunodeficiency virus-infected patients had pleural effusions and
      27 of the 28 were suffering from concomitant pulmonary diseases. Those diseases
      were bacterial pneumonia (9), mycobacterial infection (7), non-Hodgkin's lymphoma
      (4) and Kaposi's sarcoma (2). Pneumocystis carinii pneumonia was diagnosed in two
      patients, and cytomegalovirus pneumonitis and pulmonary aspergillosis and small
      cell carcinoma in one patient each. Cytologic examination of pleural effusions
      provided conclusive diagnoses of mycobacterial infection in 2 of the 7 patients,
      of non-Hodgkin's lymphoma in 4 and of P carinii infection in 2.

PMID- 7631545
TI  - Value of ultrastructural studies in fine needle aspiration biopsy diagnosis.
AB  - We studied 156 fine needle aspiration biopsies of tumors from various locations
      with electron microscopy and, after processing, obtained evaluable material in 99
      (63%) cases. Ultrastructural study elicited highly significant or essential
      findings in 39 patients (39% of the evaluable samples). In the cases requiring
      urgent treatment we were able to obtain an ultrastructural diagnosis in seven
      hours.

PMID- 7631546
TI  - Diagnostic value of p53 protein in the study of serous effusions.
AB  - The differential diagnosis between neoplastic and reactive mesothelial cells is
      one of the most frequent problems in the study of serous effusions. We assessed
      the utility of the immunohistochemical determination of p53 protein as a marker
      of malignancy in 34 embedded blocks of neoplastic fluids and 30 nonneoplastic
      effusions. Eleven (32.4%) of the tumor fluids were positive for this antibody,
      while all the nonneoplastic fluids were negative. A specificity of 100% and a
      sensitivity of 59% were observed. The immunohistochemical determination of p53
      protein seems to be helpful in the differential diagnosis of effusions; its
      principal limitation is its relatively low sensitivity.

PMID- 7631547
TI  - Cytologic diagnosis of upper urinary tract neoplasms by ureteroscopic sampling.
AB  - During a three-year period, 160 cytologic specimens from the upper urinary tract
      (UUT) were collected from 62 patients. The specimens were obtained during
      ureteroscopy using various sampling techniques, including washing, brushing,
      aspiration and minute biopsies. The patients ranged from 17 to 84 years of age
      and consisted of 32 men and 30 women. For each patient one diagnosis that
      indicated the highest degree of abnormality was selected. These consisted of 23
      "malignant," 9 "suspicious for malignant," 19 "atypical," 8 "negative for
      malignancy" and 3 "unsatisfactory" diagnoses. Of 30 patients with a malignant or
      suspicious diagnosis for whom adequate clinical and follow-up information was
      available, 18 had histologic confirmation of malignancy, and the other 12 had
      clinical and endoscopic evidence of neoplasms. Of 15 patients with an atypical
      diagnosis and adequate follow-up, 2 proved to have low grade transitional cell
      carcinoma, 1 had a fibroepithelial polyp, and 12 had clinical, endoscopic and
      follow-up evidence of nonneoplastic conditions. None of the 11 cases with
      negative or unsatisfactory diagnoses was found to have a malignant neoplasm.
      Because of the difficulty in obtaining adequate biopsies from UUT lesions,
      cytologic examination is the most practical method of diagnosis. This study
      indicated that highly accurate results are achieved, with close correlation
      between endoscopic and cytologic findings.

PMID- 7631549
TI  - Bile cytology. Diagnostic role in the management of biliary obstruction.
AB  - Thirty satisfactory bile specimens from 21 patients (13 with cancer and 8 with
      benign conditions) were reviewed to assess the diagnostic role of bile cytology
      in the management of biliary obstruction. Smears were malignant in 5 instances,
      suspicious in 1, atypical in 2 (8 in the positive group) and negative in 22.
      There were no false positives. The diagnostic sensitivity was 38%, specificity
      100% and overall accuracy 57%. Of interest were (1) hepatocellular carcinoma,
      causing obstruction in three patients; (2) metastatic colonic adenocarcinoma,
      causing obstruction in another instance; (3) positive cytodiagnosis in a patient
      who developed biliary stricture following laparoscopic cholecystectomy; and (4)
      detection of acidfast bacilli in bile from a case of tuberculous pseudotumor
      mimicking a hepatic malignancy. Bile cytology is a simple, inexpensive means of
      obtaining tissue confirmation of neoplastic and specific inflammatory causes of
      biliary obstruction. It is a useful adjunct to other techniques in this era of
      fiberoptic diagnostic procedures. Cell block sections should be prepared whenever
      possible.

PMID- 7631548
TI  - Human papillomavirus in cell samples from Stockholm Gynecologic Health Screening.
AB  - We compared the results of cytologic screening of 500 women in the Stockholm
      Gynecologic Health Control with human papillomavirus (HPV) detection by
      polymerase chain reaction (PCR) and in situ hybridization (ISH). There were two
      main age groups, one 30 years and younger and the other 40 years and older. There
      were relatively more women with HPV infection in the younger group than in the
      older one (15.7% as compared to 11.1%), but the difference was not significant in
      our material. Most cases (8/12) with cytologic atypia were HPV positive by PCR.
      HPV type 16 was most common, followed by types 31 and 18. HPV of unknown types
      was detected in 43.7% of HPV-positive cases. There was excellent agreement
      between PCR and ISH in detecting and typing HPV.

PMID- 7631550
TI  - Image-directed percutaneous biopsy with large-core needles. Comparison of
      cytologic and histologic findings.
AB  - Large biopsy needles (18 and 19 gauge) have been reported to yield high-quality
      tissue cores for reliable histologic diagnosis. In our institution, image
      directed percutaneous biopsy specimens obtained with these needles are processed
      routinely for simultaneous cytologic and histologic analysis. For the present
      study, we reviewed our experience with 82 such biopsies of the thoracoabdominal
      region. We examined the value of cytologic analysis as a supplement to histologic
      analysis of such biopsies in terms of diagnostic yield and sensitivity for
      detecting malignancy. Among the 82 specimens, material was adequate for
      histologic diagnoses in 70 (85%) and for cytologic diagnosis in 63 (77%).
      Combining the histologic and cytologic results increased the diagnostic yield to
      93% (76 of 82 specimens). Forty-eight lesions were diagnosed as malignant by
      either one or both means of analysis. While histologic analysis produced 44 of
      the 48 positive results (92%), cytologic analysis produced 33 (66%) (P < .05,
      McNemar's test). Because tissue fragments were selected preferentially for
      histologic processing, histologic evaluation was more valuable than cytologic
      evaluation in achieving definitive diagnoses of malignancy. In spite of this bias
      in preparation technique, malignancy was diagnosed by cytologic analysis alone in
      4 of the 48 positive cases (8%). We conclude that the combined approach of
      histologic and cytologic examination of large-gauge core needle biopsy specimens
      maximizes the diagnostic yield and sensitivity for detecting malignancy.

PMID- 7631551
TI  - Fine needle aspiration cytodiagnosis of subcutaneous fat necrosis of newborn. A
      case report.
AB  - We recently diagnosed subcutaneous fat necrosis in a newborn female infant using
      fine needle aspiration cytology. The neonate had perinatal asphyxia and her
      mother a difficult labor, but otherwise the neonate was well developed and
      healthy and within a few days developed well-defined areas of subcutaneous
      induration all over. On cytologic examination of the aspirated material, many
      necrotizing fat cells were found with refractile, needle-shaped crystals arranged
      in a sheaflike or starburst pattern. Subcutaneous fat necrosis of the newborn is
      uncommon today, and although the histologic findings from excised tissue are
      known, this appears to be the first case in which the diagnosis was possible from
      a sample of fine needle aspirate.

PMID- 7631552
TI  - Fine needle aspiration cytology of Tay-Sachs disease. A case report.
AB  - The fine needle aspiration cytology (FNAC) brain findings on a 6-year-old with
      Tay-Sachs disease are presented. These findings were compared with the FNAC
      findings on identical areas of a normal brain. Copious material was obtained from
      both cases. Marked loss of neurons, prominent gliosis, reactive microglia and
      scattered macrophages were hallmarks of Tay-Sachs disease. The findings were the
      same as those observed in the histopathology of Tay-Sachs disease. The normal
      brain, as expected, showed no such changes. It is concluded that FNAC has a great
      potential for diagnosis and follow-up of Tay-Sachs disease and other
      nonneoplastic neurologic diseases.

PMID- 7631553
TI  - Cytology of cervical chordoma in cerebrospinal fluid from a child. A case report.
AB  - The cytologic findings on cerebrospinal fluid examination of cervical chordoma in
      a 2-year-old girl are presented. The major cell type was a small, isolated,
      hyperchromatic cell with sharply defined nuclear membrane and granular cytoplasm.
      However, the characteristic cell of this neoplasm, the so-called physaliferous
      cell with typical bubbly cytoplasm, was also noted. Cytologic findings were
      compared to biopsy findings, with a good correlation of tumor morphology.
      Clinical follow-up revealed unusually aggressive tumor behavior, and the patient
      died a year later despite intensive chemotherapy. The differential diagnosis of
      the condition is also discussed.

PMID- 7631554
TI  - Diffuse tenosynovial giant cell tumor of soft tissues. Report of a case with
      cytologic and cytogenetic findings.
AB  - Extraarticular diffuse tenosynovial giant cell tumor is an unusual lesion the
      cytologic picture of which has not been discussed much in the literature. Fine
      needle aspiration biopsy of a nonpainful mass in the right shoulder in an 18-year
      old woman revealed a highly cellular lesion consisting of polygonal cells and
      multinuclear giant cells with scant nuclear pleomorphism and a marked tendency
      toward xanthomization. Electron microscopy identified two basic cell populations
      among many intermediate forms: cells with scant filopodia and abundant ribosomes
      and cells with well-developed prolongations and numerous mitochondria, lysosomes
      and lipid drops. The karyotype of the tumor cells obtained from a surgically
      excised specimen showed a clonal population with 45, XX, t(1;2) (pter->p22::q24
      >pter), t(1:14)(qter->p13::q13->ter). The cytologic differential diagnosis
      included other tenosynovial lesions containing xanthomatous cells. Cytogenetic
      findings are discussed in relation to chromosomal alterations previously found in
      related lesions (nodular tenosynovitis and pigmented articular villonodular
      synovitis).

PMID- 7631555
TI  - Fine needle aspiration of the spleen in hairy cell leukemia. A case report.
AB  - Hairy cell leukemia (HCL), or leukemic reticuloendotheliosis, first described by
      Bouroncle in 1958, is a chronic lymphoproliferative disorder of B-cell origin
      that is manifest primarily in the blood, marrow and spleen. The hairy cells often
      contain a tartrate-resistant acid phosphatase (TRAP) isoenzyme and show prominent
      cytoplasmic projections. We report a rare case of hairy cell leukemia wherein the
      total white blood cell count in the peripheral blood was 20 x 10(9)/L, there were
      hairy cells in the peripheral blood, and the bone marrow aspirate was a dry tap.
      Fine needle aspiration of the spleen was performed. The splenic smears showed a
      monotonous population of abnormal lymphoid cells, some with the hairlike
      cytoplasmic projections. TRAP staining was positive. HCL must be differentiated
      from splenic B-cell lymphoma with circulating villous lymphocytes.

PMID- 7631556
TI  - Ciliated hepatic foregut cyst. Report of a case with findings on fine needle
      aspiration.
AB  - Ciliated hepatic foregut cyst (CHFC) is an uncommon cystic lesion of the liver.
      It is analogous in nature and pathogenesis to the bronchial cysts that occur in
      the mediastinum. We report a case of CHFC diagnosed on fine needle aspiration
      (FNA) with a discussion of the cytologic findings and features and a review of
      the literature. Abdominal computed tomography (CT) detected the lesion during a
      workup for metastatic squamous cell carcinoma of the cervix in a patient with an
      intrauterine contraceptive device and uterine Actinomyces infection. Subsequent
      CT-guided FNA produced clear, viscid material that revealed numerous macrophages
      and scattered ciliated columnar cells within the mucinous background. The
      cytology and radiologic findings were essentially similar to those of a bronchial
      cyst and did not conform to any of the findings in generally known lesions of the
      liver. Awareness of this rare hepatic lesion will result in an accurate and
      definitive diagnosis by guided FNA biopsy and avoidance of surgical exploration
      and excision biopsy.

PMID- 7631557
TI  - Fibroadenoma of ectopic breast tissue in the vulva. A case report.

PMID- 7631558
TI  - Granulomatous inflammation related to amyloid deposition in a focus of multiple
      myeloma. Report of a case with diagnosis by fine needle aspiration biopsy.
AB  - A 61-year-old man with no prior history of serious illness presented with a lytic
      rib lesion. The radiographic differential diagnosis included multiple myeloma, a
      metastasis and a focal infectious process, such as tuberculosis or actinomycosis.
      Fine needle aspiration biopsy of the mass yielded an unusual smear pattern that
      included small lymphocytes, plasma cells, multinucleate giant cells, granulomas
      and amorphous eosinophilic material. These seemingly unrelated elements suggested
      the possibility of a chronic inflammatory lesion of bone, such as osteomyelitis,
      but ultimately proved to represent multiple myeloma with granulomatous
      inflammation related to amyloid deposition. The case demonstrates that the
      differential diagnosis of chronic granulomatous inflammation with numerous plasma
      cells, in the appropriate clinical context, includes amyloid in association with
      a plasma cell dyscrasia.

PMID- 7631559
TI  - Penicillium marneffei infection in patients infected with the human
      immunodeficiency virus. A report of two cases.
AB  - We present the cytologic and histologic features of two cases of Penicillium
      marneffei (PM) infection occurring in human immunodeficiency virus-positive
      patients following a journey to endemic areas. PM closely resembles Histoplasma
      capsulatum, in both its morphology and tissue reactions. Distinctive histologic
      features and culture provide the definitive diagnosis. The presence of a PM
      infection in a human immunodeficiency virus-positive patient returning from an
      endemic area should be considered an acquired immunodeficiency syndrome-defined
      illness.

PMID- 7631560
TI  - Fine needle aspiration cytology of a male breast carcinoma exhibiting
      neuroendocrine differentiation. Report of a case with immunohistochemical, flow
      cytometric and ultrastructural analysis.
AB  - We present the cytologic, immunohistochemical, flow cytometric and
      ultrastructural findings of a case of invasive ductal carcinoma of the breast
      with features of neuroendocrine differentiation occurring in an 83-year-old male.
      Fine needle aspiration (FNA) cytology of the patient's tumor demonstrated a
      markedly cellular specimen to discohesive tumor cells, present primarily singly,
      with occasional loose groups. The cells were relatively large, with pleomorphic,
      eccentrically placed, round to oval nuclei. The cytoplasm was abundant and
      contained prominent red granules (Papanicolaou stain) that were also
      argyrophilic. Immunohistochemical studies performed on the aspirate and the
      subsequently excised malignant breast tissue revealed positive staining for
      neuron-specific enolase, chromogranin A, synaptophysin and gastrin. Also, the
      majority of the tumor stained positive with antibodies to both estrogen and
      progesterone hormone receptors. DNA flow cytometry demonstrated an aneuploid
      stemline population with a DNA index of 1.73 and an S-phase fraction of 4.5%.
      Electron microscopy was performed on the FNA material, and numerous variable
      sized, membrane-bound, dense-core granules diffusely scattered within the
      cytoplasm of the neoplastic cells were identified. The specific cytologic
      features of this tumor, along with the immunocytochemical and ultrastructural
      features, can aid the pathologist in rendering an accurate FNA diagnosis of this
      specific subtype of breast carcinoma.

PMID- 7631562
TI  - Solitary angiomyolipoma of the liver. Report of a case with diagnosis by fine
      needle aspiration biopsy.
AB  - Solitary angiomyolipoma is a benign tumor that rarely develops in the liver. The
      preoperative diagnosis of this lesion is of great value because of the
      therapeutic implications. Radiologic findings are relatively characteristic but
      not specific. A case of giant angiomyolipoma of the liver is described in which
      ultrasonography, computed tomography and magnetic resonance imaging were
      insufficient to establish the diagnosis. Fine needle aspiration biopsy (FNAB) was
      performed, showing bundles of smooth muscle cells intermingled with fat mature
      cells, characteristic of this lesion. FNAB may be a valuable method of
      establishing a definitive diagnosis of hepatic angiomyolipoma.

PMID- 7631561
TI  - Cytomorphology of subcutaneous cysticercosis. A report of 10 cases.
AB  - The findings of fine needle aspiration cytology (FNAC) of subcutaneous
      cysticercosis are described. Nine patients had a single subcutaneous nodule. One
      patient had multiple skin and cerebral nodules that were clinically suspected due
      to cysticercus. Patients with a single nodule in the extremities and trunk were
      clinically diagnosed as having lipoma (1), fibroma (3) and neurofibroma (3).
      Tuberculous lymphadenitis was suspected in two cases with a single cervical
      nodule. The characteristic cytomorphology of parasitic tegument and parenchyma
      helped identify the larvae in the cytological smears, as did a polymorphous
      inflammatory reaction. Biopsy was done in four cases. Six patients were lost to
      follow-up. Histopathology of the nonaspirated nodule from the case with multiple
      skin nodules showed cysticercus. The other three biopsies showed a parasitic
      granuloma only. Of the four biopsied cases, only two underwent computed
      tomographic scans, which showed cerebral involvement. In a developing country
      like India, a rapid, safe and reliable cytologic diagnosis of subcutaneous
      cysticercus by FNAC on an outpatient basis proves to be a cost-effective
      procedure since it obviates the need for open biopsy.

PMID- 7631563
TI  - Diagnosis of ameloblastoma of the maxilla by fine needle aspiration. A case
      report.
AB  - Ameloblastoma is a tumor of odontogenic epithelium that occurs in the jaws. We
      describe a case of an ameloblastoma of the maxilla that was diagnosed by fine
      needle aspiration cytology. The patient presented with a mass in the left
      maxillary sinus. Cytologic examination of the aspirate material showed numerous
      sheets of tightly packed basaloid cells. Several sheets of cells were surrounded
      by a row of columnar cells, with the nuclei oriented away from the basement
      membrane (peripheral palisading). Histologic examination of the resection
      specimen confirmed the presence of an ameloblastoma of the maxilla.

PMID- 7631564
TI  - Cytologic diagnosis of Acanthamoeba keratitis. Report of a case with correlative
      study with indirect immunofluorescence and scanning electron microscopy.
AB  - We describe a case of Acanthamoeba keratitis in a 20-year-old woman who wore
      disposable soft contact lenses. The diagnosis was made initially on the basis of
      a periodic acid-Schiff-stained corneal smear and subsequently confirmed by
      scanning electron microscopy and immunofluorescence. The patient was successfully
      treated with a combination of 0.053% polyhexamethylene biguanide and miconazole.
      Cytologic study and culture of corneal scrapings is relatively painless and
      inexpensive and may therefore be used for successful diagnosis and follow-up.

PMID- 7631565
TI  - Oncogenous osteomalacia: fine needle aspiration of a neoplasm with a unique
      endocrinologic presentation.

PMID- 7631566
TI  - A simplified monolayer filter imprint cytology technique.

PMID- 7631567
TI  - Respiratory epithelial cells in fine needle aspirates of thyroid.

PMID- 7631568
TI  - Immunoelectron microscopic detection of chlamydial antigens in papanicolaou
      stained routine vaginal smears.

PMID- 7631569
TI  - Numerical counts of epithelial cells collected, smeared and lost in the
      conventional Papanicolaou smear preparation.

PMID- 7631570
TI  - Cryptococcal lymphadenitis: fine needle aspiration in acquired immunodeficiency
      syndrome.

PMID- 7631571
TI  - North American Drager's Narcomed 3: interlock failures.

PMID- 7631573
TI  - Violence in the workplace.

PMID- 7631572
TI  - Rene Goupil: patron saint of anesthetists.
AB  - Rene Goupil, the patron saint of anesthetists, is addressed mainly as a 17th
      century French surgeon who practiced his art in North America. He is also
      presented as a Jesuit martyr and saint. The article freely borrows from past
      writings of Jesuits on Rene Goupil.

PMID- 7631574
TI  - Conscious sedation policy development and review.

PMID- 7631575
TI  - Budget realities of the 104th Congress.

PMID- 7631576
TI  - Anesthetic implications of implanted pacemakers: a case study.
AB  - Pacemakers and the underlying pathophysiologies leading to their implantation
      present challenges to the anesthetist. This case report discusses the anesthetic
      management of a patient with an implanted pacemaker. A case is presented of an 80
      year-old female who was found unresponsive in a parking lot. She was diagnosed
      with a right parietal subdural hematoma. She underwent an emergency craniotomy
      for evacuation of the hematoma. Upon placing the patient on an
      electrocardiograph, a ventricular paced rhythm was revealed. Pacemakers are most
      frequently implanted to initiate electrical activity in a heart unable to
      maintain its own automaticity. Patients with pacemakers may be unable to react to
      situations requiring increased cardiac outputs by increasing the heart rate.
      Depending upon the type of pacemaker present, patients may suffer from diminished
      cardiac output due to the loss of the "atrial kick." Pacemakers can also be
      affected by electromagnetic interference from devices used during surgery,
      particularly the electrosurgical unit. This paper discusses anesthetic management
      in individuals with implanted permanent pacemakers.

PMID- 7631577
TI  - Thoracoscopy: anesthetic considerations.
AB  - Thoracoscopy is surgical procedure which was performed in the early 1900s
      primarily for the treatment of tuberculosis until antibiotics became the
      treatment of choice. Over the last two decades, thoracoscopy has experienced a
      rebirth as the indications for this endoscopic procedure have become numerous.
      Although less invasive than the thoracotomy, thoracoscopy is not without
      potential complications. The anesthesia provider must be alert for problems
      related to one-lung ventilation, lateral positioning, and pleural cavity
      insufflation. The anesthetic technique must be planned with the physiological
      changes which occur during thoracoscopy in mind.

PMID- 7631578
TI  - Superficial and deep cervical plexus block: technical considerations.
AB  - Regional anesthetic block of the cervical plexus is a safe and useful alternative
      to general endotracheal anesthesia for surgery of the neck, upper shoulder, and
      occipital scalp area. The sensory component of the cervical plexus can be blocked
      separately and easily by a superficial cervical plexus block. Both motor and
      sensory block can be obtained by deep cervical plexus block. Minor transient side
      effects are common to deep cervical plexus blocks, but they are rarely of any
      consequence. Recent years have seen an increase in interest in the use of the
      cervical plexus block, because its popularity for surgical procedures such as
      carotid endarterectomies has grown. An understanding of the anatomy and
      principles of this anesthetic technique will enable the clinician to offer the
      patient and surgeon an important anesthetic option.

PMID- 7631579
TI  - Nurse anesthesia admission qualifications.
AB  - This study describes criteria used by graduate nurse anesthesia educational
      programs (GNAEPs) in selecting students for admission. The investigators prepared
      and distributed a 15-item questionnaire to 71 GNAEPs as listed by the Council on
      Accreditation of Nurse Anesthesia Eduational Programs for December 1992. Thirty
      eight of 71 (54%) of GNAEPs participated in this study. Upon examination of
      standardized test scores, mean Graduate Record Exam scores were: analytical 533,
      quantitative 512, verbal 510, and cumulative 1,552. The mean Millers Analogy Test
      score was 47. The mean overall grade point average (GPA) was 3.32 and the mean
      science GPA was 3.20. Experience in critical care nursing averaged 5 years, with
      54% of students coming from surgical intensive care units and 81% Advanced
      Cardiac Life Support certified. The most commonly identified prerequisite course
      was organic/biochemistry. All programs required references, 97% required
      interviews, and 68% required essays. Program directors ranked overall GPA,
      interview, and science GPA among the factors considered most in the selection
      process. The sample revealed an acceptance rate of 22% for those applying to
      GNAEPs.

PMID- 7631580
TI  - AANA journal course: update for nurse anesthetists--anesthetic considerations for
      the burn patient.
AB  - The anesthetic management of a burn trauma patient requires practitioners to have
      a solid understanding of the pathophysiology of the burn wound, the phases of
      burn trauma management, and the anesthetic implications for each phase. This
      article addresses anesthetic considerations during the acute, surgical, and
      reconstructive phases of care of the burn victim. An overview of the effects of
      thermal injury on the body systems is presented. Surgical considerations include
      preoperative evaluation, preparation, and transport, as well as fluid and
      temperature monitoring. Anesthetic drugs and temperature monitoring. Anesthetic
      drugs and techniques are discussed, with consideration given to the special
      concerns of burn patients. The unique features of electrical injuries are
      described since these bring an added dimension to anesthesia management.

PMID- 7631581
TI  - Towards restoring sensibility in anaesthetic extremities of leprosy patients.
AB  - In leprosy patients, the problems arising due to anaesthesia in the extremities
      have been outlined. The available modalities, some of them still experimental,
      for overcoming the handicap have been discussed.

PMID- 7631582
TI  - [Status of the integration of the antileprosy campaign in the general health
      services in Senegal].
AB  - The survey on the integration of leprosy control in Senegal with the general
      health services has shown that the level of integration varies according to the
      services offered. Both strong and weak points have been detected and it is
      therefore advisable to reinforce the findings that are positive and to seek
      solutions to the problems. 82.1% of the male nurses in charge of health center
      included in the survey have already had to refer suspected cases of leprosy to
      the Leprosy Specialist for confirmation. In 85.7% of the cases, it is the Nurses
      Persons in Charge who administer the supervised dose of multidrug therapy. The
      external validity of this study is problematic; nevertheless, these results could
      still draw the attention of administrators, decision-makers, and other persons of
      influence to the problems that could curb the integration of leprosy control with
      the general health services.

PMID- 7631583
TI  - [The frequency of the appearance of perforating foot ulcers in patients with
      Hansen's disease as a function of treatment with disulone alone or with
      polychemotherapy].
AB  - Between 1986 and 1989, in 5 departments of Senegal, 436 new cases of leprosy were
      detected, of whom 225 were put under dapsone monotherapy and 211 under multidrug
      therapy (MDT). Of them, 190 could be followed-up during 2 years by means of
      annual bacteriological and clinical examination, including neurological
      assessment. In 2 years, the onset of 10 (5.3%) chronic plantar ulcers (CPU) was
      observed: 4 (4%) among the 99 patients under dapsone monotherapy and 6 (6.6%)
      among the 91 under MDT (no significant difference). Of the 10 CPU, 3 (2%)
      appeared among the 149 patients without any disability at detection while 7 (17%)
      were observed among the 41 others who presented a grade 1 disability at detection
      (p < 0.01). Of the 6 CPU appeared in the patients under MDT, 5 (22%) were
      observed among the 23 who presented a grade 1 disability at detection and 1
      (1.5%) among the 68 who did not (p < 0.01). This difference was not noted in the
      patients under dapsone monotherapy. Our results need to be confirmed by other
      studies including a higher number of patients followed-up during a longer period
      of time. Nevertheless, they suggest that MDT could prevent the onset of CPU, but
      only in patients without any disability at detection. Therefore, they reemphasize
      the importance of early detection of the disease in leprosy control programmes.

PMID- 7631584
TI  - Response of leprosy patients with single lesions to MDT.
AB  - This study reports the clinical profile and therapeutic response of seventy-two
      mono-lesions leprosy cases. These 72 cases were among 578 paucibacillary (PB)
      cases classified according to WHO (1982) and were followed-up on multidrug
      therapy (MDT). Of these 72 mono-lesion cases, 46 (64%) were tuberculoid (TT)
      cases, 24 (33%) were Indeterminate (Ind) cases and 2 (3%) were of borderline
      tuberculoid (BT) types. While 37.5% of these cases presented as macular patches,
      the remaining 62.5% had raised erythematous lesions. In majority of cases (94%),
      the lesions were present on the exposed parts like legs and feet, arms and hands,
      face, whereas only 6% presented on covered areas of trunk and buttocks. These
      cases were treated with dapsone 100 mg daily for 12 months and rifampicin 600 mg
      once a month for 6 months. After 6 months of MDT, lesions in 81% of the patients
      regressed clinically and by one year of therapy 96% of cases had regressed.
      Treatment was stopped in all cases by one year of therapy. There were no relapse
      or late reaction in the 5 years of post treatment follow-up. The response of mono
      lesion PB cases was better than the multi-lesions PB cases at 6 months and during
      the post treatment follow-up period.

PMID- 7631585
TI  - [Antileprosy polychemotherapy in the member states of the OCCGE: a decade of
      implementation (1983-19930). The National Coordinators of the Leprosy Program of
      the 8 states of the OCCGE].
AB  - MDT for leprosy recommended by WHO in 1981 has been introduced and implemented in
      8 Member States of OCCGE (an organization for leprosy control in francophone West
      Africa). This implementation from 1983 to 1993 can be divided in two phases: 1983
      1987: introduction phase by pilot projects; 1988-1993: extension phase by
      national leprosy control programmes. During the ten years, MDT coverage rose to
      68%, leprosy prevalence rate widely decreased (40.71 to 6.56 per 10,000), while
      annual detection rate weakly varied (1.89 to 1.26 per 10,000). Factors
      influencing this evolution of leprosy are brought out and recommendations are
      made about strategies to be developed for leprosy control up to year 2000.

PMID- 7631586
TI  - AIDS and tuberculosis/leprosy in Nigeria: the urbanisation factor.
AB  - A study was conducted between February and June 1994 on the influence of
      urbanisation on the seroprevalence of human immunodeficiency virus (HIV) amongst
      tuberculosis (TB) and leprosy patients in the 4 Primary Health Care Zones in
      Nigeria. Results indicate that 71.4% of all smear positive TB patients and 75% of
      all multibacillary (MB) leprosy patients that are HIV seropositive in this study
      are resident in the urban areas. This study emphasizes the need for careful
      sample selection in studies involving HIV and tuberculosis/leprosy, and for
      careful monitoring of the HIV/leprosy interactions.

PMID- 7631587
TI  - Bibliography.

PMID- 7631588
TI  - [Topical steroids and rhinitis].

PMID- 7631589
TI  - Uses, adverse effects of abuse of corticosteroids. Part II.

PMID- 7631591
TI  - Phenotypes of alpha-1-antitrypsin in intrinsic asthma and ASA-triad patients.
AB  - The frequency of presence of various phenotypes of alpha 1-antitrypsin was
      studied in 31 patients with intrinsic asthma and 11 with ASA-Triad, and compared
      to a group of 200 people representative of the general population. The MZ and SZ
      phenotype is more frequent in intrinsic asthmatics (p < 0.00001) and MZ in ASA
      Triad (p < 0.0005) than in the control group. No differences were found between
      the intrinsic asthmatics and ASA-Triad. All the patients were divided into groups
      according to their clinical characteristics and an increase of the MZ phenotype
      was observed (p < 0.001) in patients with: nasal polyposis, intolerance to non
      steroidal anti-inflammatories, a family history of atopy and peripheral
      eosinophilia (p < 0.01). Alpha-1-antitrypsin deficiency could be important in the
      pathogenesis of inflammatory processes and in the clinical manifestations
      characteristic of patients with intrinsic asthma and ASA-Triad.

PMID- 7631590
TI  - Aerobiology of inhalatory allergen carriers.

PMID- 7631592
TI  - Screening for atopy in a coffee processing factory.
AB  - Screening for blood IgE mediated allergy (atopy) by the RAST technique among 76
      people working in a coffee processing factory showed rather unexpected findings:
      although we found a prevalence of positivity (17.1%) to the common airborne
      antigens (pollens, mites, cat, Alternaria tenuis) which was close to the
      prevalence of atopy among normal adults in our area (19.3%), only one case of
      allergy to green coffee and two cases to castor bean came to the fore. Specific
      IgG4 antibodies were measured only for castor bean and green coffee, and rather
      elevated figures were found: green coffee 17.1%, castor bean 13.1%. The occurence
      of positive RASTs to castor bean is more likely to be due to contamination of the
      bags containing green coffee. The low prevalence of RAST positivities to green
      coffee, and the elevated specific IgG4 antibodies to both castor bean and green
      coffee antigens, raise several possibilities which are discussed; however, all
      the subjects but one having elevated specific IgG4 levels to green coffee worked
      in more exposed areas. Probably IgG4 antibodies in this particular case are
      acting as blocking antibodies.

PMID- 7631593
TI  - Odor-associated idiopathic anaphylaxis. A case report.
AB  - A 44 year old woman is described who appears to have idiopathic anaphylaxis
      triggered by chemical odors. Her case and a general discussion of anaphylaxis are
      presented. The known causes of anaphylaxis and a discourse on idiopathic
      anaphylaxis are given. The treatment of idiopathic anaphylaxis is discussed.

PMID- 7631594
TI  - Bronchial asthma induced by hypersensitivity to legumes.
AB  - We report the case of a 54-year-old female patient, diagnosed of nasal polyposis
      and intrinsic corticodependent bronchial asthma, who since a year has developed
      episodes of asthma when exposed to vapours from cooking some kinds of legumes
      (peas, chick-peas, beans, lentils) and an oral allergy syndrome with peanuts. We
      prepared extract with these legumes. The skin tests were clearly positive for
      legumes but negative for pneumoallergens. Specific IgE by CAP was strongly
      positive for legumes. CAP inhibition was preformed and the results show the
      presence of cross-reactivity among legumes.

PMID- 7631595
TI  - Evaluation of serum specific IgE and skin responsiveness to allergenic extracts
      of Oleaceae pollens (Olea europaea, Fraxinus excelsior and Ligustrum vulgare) "in
      patients with respiratory allergy.
AB  - In the last few years an increasing interest for Olea europaea (O.e.) pollen has
      been developed in many countries. Several authors have studied the
      aerobiological, allergenic, epidemiological and clinical features of this
      pollinosis. The aim of our study was to evaluate cutaenous and serological
      responses to other oleaceae pollens allergens (Ligustrum vulgare (L.v.) and
      Fraxinus excelsior (F.e.) in patients with skin positivity to Olea europaea
      pollen extract. Twenty-three atopic rhinitis and/or asthmatic patients living in
      Naples area and with immediate positive skin reaction only to O.e. pollen extract
      were examined. Patients were tested by skin prick test (SPT) for O.e., F.e. and
      L.v. with glycerinated allergenic extracts. Serum enzyme immunoassay for the same
      allergens was also performed. We found a statistically significant correlation
      between the results of SPT and of specific IgE assay for Oleaceae pollens as well
      as between the results of the in vivo vs in vitro tests. We suggests the utility,
      in patients with O.e. pollinosis who travel in Northern europe, to plan SPT
      and/or specific IgE determinations also with F.e. and L.v. allergenic extracts
      for the possibility of developing a nasal and/or bronchial symptomatology after
      the inhalation of these pollen grains.

PMID- 7631596
TI  - Prediction of acute coronary syndromes by percutaneous coronary angioscopy in
      patients with stable angina.
AB  - To pinpoint the link between plaque characteristics and acute coronary syndromes,
      we performed a 12-month prospective follow-up study in 157 patients with stable
      angina pectoris in whom regular coronary plaques were observed by percutaneous
      coronary angioscopy. Acute coronary syndromes occurred more frequently in
      patients with yellow plaque than in those with white plaques (11 of 39 vs 4 of
      118; p = 0.00021). Moreover, the syndromes occurred more frequently in patients
      with glistening yellow plaques than in those with nonglistening yellow plaques (9
      of 13 vs 2 of 26; p = 0.00026). Thrombus arising from the ruptured identical
      plaques was confirmed by angioscopy as the culprit lesion of the syndromes. The
      results indicate that acute coronary syndromes occur frequently and in a short
      time in patients with glistening yellow plaques and that angioscopy but not
      angiography is feasible for prediction of the syndromes.

PMID- 7631597
TI  - Endogenous cytokine antagonists during myocardial ischemia and thrombolytic
      therapy.
AB  - We tested the idea that cytokine antagonists are released during acute myocardial
      ischemia to counteract proinflammatory effects of cytokines. We investigated
      changes in plasma concentrations of the anticytokine molecules alpha-melanocyte
      stimulating hormone (alpha-MSH), interleukin-1 receptor antagonist (IL-1ra), and
      soluble tumor necrosis factor receptor (sTNFr) in patients with acute myocardial
      infarction (AMI) or unstable angina (UA). Blood samples were collected at
      presentation in the coronary care unit, at 3-hour intervals for 24 hours, and
      daily for 4 days thereafter. There were no significant differences in the
      concentrations of cytokine antagonists in patients with AMI or UA. However,
      whereas concentrations of alpha-MSH were increased in early samples of patients
      with AMI or UA who were treated with a thrombolytic agent, they were consistently
      low in untreated patients. IL-1ra concentrations likewise were greater 3 and 6
      hours after treatment in patients who underwent thrombolysis, whereas there was
      no significant difference in plasma sTNFr between the two groups. We suggest that
      during myocardial ischemia and thrombolysis anticytokine molecules released from
      the injured myocardium become available to reduce inflammation caused by
      cytokines and other mediators of inflammation.

PMID- 7631598
TI  - Clinical and angiographic correlates of normal creatine kinase with increased MB
      isoenzymes in possible acute myocardial infarction.
AB  - A retrospective study of patients with possible acute myocardial infarction was
      conducted over a 2-year period to evaluate the clinical characteristics,
      angiographic findings, and in-hospital prognosis in patients with normal total
      creatine kinase (CK) activity and increased MB isoenzyme activity (CK-MB). Thirty
      nine cases were identified (study group) and compared with cases of Q-wave (n =
      77) and non-Q-wave (n = 60) infarctions. Compared with the Q-wave group, study
      group patients were older (67.5 +/- 9.0 vs 60.8 +/- 11.5 years; p < 0.01) and
      more often had previous diagnoses of coronary disease (52.6% vs 18.2%; p < 0.01)
      and peripheral vascular disease (28.9% vs 10.4%; p = 0.02). Angina (92.2% vs
      65.8%; p < 0.01) and ST elevation (81.8% vs 13.2%; p < 0.01) were more common in
      the Q-wave group. Nearly identical clinical profiles and electrocardiographic
      findings were observed in the study and non-Q-wave groups. Angiographic analysis
      revealed a higher frequency of multivessel disease in the study group (89.6%)
      than in the Q-wave group (48.6%, p < 0.01) but no difference between the study
      group and the non-Q-wave group (79.6%; p not statistically significant). Left
      ventricular function and in-hospital complications were similar among groups. It
      is concluded that patients with normal total CK activity and increased CK-MB
      concentration represent a subgroup of patients with non-Q-wave infarction with a
      high prevalence of multivessel coronary disease.

PMID- 7631599
TI  - Angiographic, ultrasonic, and angioscopic assessment of the coronary artery wall
      and lumen area configuration after directional atherectomy: the mechanism
      revisited.
AB  - The purpose of the present study was to use the complementary information of
      angiography, intravascular ultrasound, and intracoronary angioscopy before and
      after directional atherectomy to characterize the postatherectomy appearance of
      vessel wall contours and the mechanism of lumen enlargement. Directional coronary
      atherectomy aims at debulking rather than dilating a coronary artery lesion. The
      selective removal of the plaque may potentially minimize the vessel wall damage
      and lead to subsequent better late outcome. Whether plaque removal is the main
      mechanism of action has only to be assessed indirectly by angiography and
      warrants further investigation with detailed analysis of luminal changes and
      vessel wall damage by ultrasound and direct visualization with angioscopy. Twenty
      six patients have been investigated by quantitative angiography, intravascular
      ultrasound, and intracoronary angioscopy (n = 19) before and after atherectomy.
      In addition, all retrieved specimens were microscopically examined. Ultrasound
      imaging showed an increase in lumen area from 1.95 +/- 0.70 mm2 to 7.86 +/- 2.16
      mm2 at atherectomy. The achieved gain mainly resulted from plaque removal because
      plaque plus media area decreased from 18.16 +/- 4.47 mm2 to 13.13 +/- 3.10 mm2.
      Vessel wall stretching (i.e., change in external elastic lamina area) accounted
      for only 15% of lumen area gain. Luminal gain was higher in noncalcified (6.52 +/
      2.12 mm2) lesions than in lesions containing deeply located calcium (5.19 +/-
      0.99 mm2) and lowest in superficially calcified lesions (5.41 +/- 2.41 mm2).
      Ultrasound imaging identified an atherectomy byte in 85% of the cases, whereas
      angioscopy revealed such a crevice in 74%. The complementary use of the three
      techniques revealed an underestimation of the presence of dissection/tear and new
      thrombus by angiography (10% and 4%) and ultrasound imaging (12% and 0%) compared
      with angioscopy (26% and 21%). The combined use of angiography, ultrasound, and
      angioscopy reveals that the postatherectomy luminal lining is not as regular and
      smooth as that seen by angiography. Luminal enlargement with atherectomy is
      achieved by plaque excision rather than arterial expansion.

PMID- 7631601
TI  - Clinical significance of no-reflow phenomenon observed on angiography after
      successful treatment of acute myocardial infarction with percutaneous
      transluminal coronary angioplasty.
AB  - The clinical significance of the angiographic no-reflow phenomenon was evaluated
      in 93 patients with acute myocardial infarction treated by percutaneous
      transluminal coronary angioplasty (PTCA). On the basis of the post-PTCA
      angiograms, patients were divided into three groups: normal angiogram (group 1, n
      = 65), slight no-reflow (group 2, n = 13), and severe no-reflow (group 3, n =
      15). Regional wall motion in the chronic phase was depressed in groups 2 and 3
      compared with group 1. The proportion of the area of the transmural infarction to
      that of the total infarction determined by scintigraphy was higher in groups 2
      and 3 than in group 1. A significantly higher incidence of myocardial rupture and
      of death resulting from cardiac causes was observed in group 3 compared with
      group 1. The severity of this phenomenon immediately after an emergency PTCA
      correlated well with the severity of myocardial damage, with patients having
      severe no-reflow showing the poorest prognosis.

PMID- 7631600
TI  - Guidance of anticoagulation after intracoronary implantation of Palmaz-Schatz
      stents by monitoring prothrombin and prothrombin fragment 1 + 2.
AB  - The primary objective of this study was to apply a sophisticated coagulation
      monitoring system including estimation of the concentration of prothrombin
      fragment 1 + 2 (PTF 1 + 2) and the activity of prothrombin (coagulation factor II
      or FII) to cases of stent implantation and to compare the results with those of
      standard coagulation tests. The secondary objective was to detect the incidence
      after stenting of subacute thrombosis (SAT) and bleeding complications in these
      patients and to compare the results with those of a group of patients with stent
      implantation in whom coagulation was monitored exclusively by standard tests. SAT
      several days after coronary stenting occurs in up to 20% despite aggressive
      intravenous and overlapping oral anticoagulation. According to a prospective
      study protocol 120 consecutive patients with implantation of 155 Palmaz-Schatz
      stents underwent coagulation monitoring including single daily estimation of the
      concentration of PTF1 + 2 (target range < 0.5 nmol/L) and of FII activity (15% to
      35%) in addition to the standard tests of thrombin time (TT), partial
      thromboplastin time (aPTT), international normalized ratio (INR), antithrombin
      III (ATIII), and fibrinogen. Adjustment of heparin and phenprocoumon dosages in
      this study group was based only on the results of PTF1 + 2 and FII measurements.
      A control group consisted of 53 patients with implantation of 64 stents who were
      matched for baseline, angiographic, and procedure-related characteristics. After
      stenting, anticoagulation was monitored by estimation of TT (target range > 70
      seconds), aPTT (> 70 seconds), INR (3.0 to 4.5), AT III (> 80%), and fibrinogen
      (< 450 mg/dl) in this control group. There was a weak correlation between PTF1 +
      2 and aPTT (r = 0.337; PTF1 + 2 = -0.00169aPTT + 0.491) and PTF1 + 2 and TT (r =
      0.328; PTF1 + 2 = -0.00142TT + 0.494). A better correlation was found between FII
      and INR (r = 0.983; FII = -23.8 INR + 134). Stable oral anticoagulation was
      maintained 2.8 +/- 0.9 days later according to an FII concentration of < 35%
      compared with an INR > 3. The incidence of SAT was 3.3% with 3.0% for elective
      versus 3.8% for nonelective stenting. The sensitivity, specificity, and accuracy
      of the PTF1 + 2 test were 100%, 88%, and 88%, respectively. In the control group
      the incidence of SAT was 17%, with 16.1% for elective versus 18% for nonelective
      stenting. Major bleeding complications occurred in 10% (study group) and in 11.3%
      (control group) of patients (no statistical difference).(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 7631602
TI  - Effects of antecedent anginal episodes and coronary artery stenosis on left
      ventricular function during coronary occlusion.
AB  - We evaluated the effects of antecedent anginal episodes and coronary artery
      stenosis on left ventricular function during coronary occlusion and the role of
      collateral filling in 33 patients with angina pectoris who underwent angioplasty.
      Wall motion abnormalities were investigated by echocardiography and classified
      into hypokinesia and akinesia. Collateral filling during angioplasty was
      evaluated by using a second artery catheter. Akinesia was observed as follows:
      24% of the patients had > 30 anginal episodes, 38% had 5 to 30, and 87% of the
      patients had < 5 (p < 0.01); 12% of patients had a lesion of 99%, 47% had a
      lesion of 90%, and 83% had a lesion of 75% (p < 0.05). Akinesia was observed in
      none of the patients with grade 3 collaterals, 57% with grade 2, and 67% with
      grade 1 or 0 (p < 0.01). These observations suggest that the patients with
      antecedent frequent anginal episodes and severe coronary stenosis have less left
      ventricular dysfunction during coronary occlusion. This finding may be the result
      of more extensive collateral development.

PMID- 7631603
TI  - Effect of beta-adrenergic receptor blockade on the physiologic response to
      dobutamine stress echocardiography.
AB  - Dobutamine is an effective pharmacologic stress agent because of its beta
      adrenergic receptor agonist properties. Theoretically, concurrent beta-adrenergic
      receptor blockade might alter this effectiveness, but clinical experience has
      been variable. Before assessing the relative effectiveness and implications of
      dobutamine stress echocardiography (DSE) to detect myocardial ischemia in the
      presence of beta-blockade the physiologic and hemodynamic effects of dobutamine
      with simultaneous beta-blockade must be understood in a controlled setting.
      Therefore the purpose of this study was to determine if beta-blocking agents
      alter the timing and magnitude of the physiologic response to graded doses of
      dobutamine during a standard DSE. Paired DSEs were performed in seven
      instrumented open-chest dogs with and without beta-blockade (esmolol 500
      micrograms/kg initial bolus and 100 micrograms/kg/min infusion). Heart rate,
      systolic pressure, proximal left anterior descending coronary artery flow,
      myocardial thickening, and percentage left ventricular area change (% AC) were
      monitored. The data for each parameter were fit to linear or exponential
      functions. With graded doses of dobutamine, the rate of increase in coronary flow
      was greater than that in %AC, which in turn was greater than that in heart rate
      (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7631604
TI  - Intravenous albunex during dobutamine stress echocardiography: enhanced
      localization of left ventricular endocardial borders.
AB  - Albunex is an intravenous contrast agent that opacifies the left ventricle (LV).
      This study evaluated the effect of Albunex on the enhancement of LV endocardial
      border localization during dobutamine stress echocardiography (DSE). Albunex was
      infused in 30 patients at baseline and with low- and high-dosage dobutamine.
      Apical two- and four-chamber views were divided into six segments each, and
      enhancement of LV border localization was compared with precontrast images graded
      as follows: 0 = none; 1 = faint; or 2 = optimal. The mean grade and percentage of
      segments with optimal localization of LV endocardial borders were determined.
      There was a significant increase in enhancement with low- and high-dosage
      dobutamine when compared with baseline. Of 179 segments with suboptimal
      enhancement at baseline, 137 (77%) became optimal during DSE with Albunex. We
      conclude that Albunex improves localization of LV endocardial borders and that
      this localization is enhanced during DSE.

PMID- 7631605
TI  - Limited prognostic value of thallium-201 exercise treadmill testing early after
      myocardial infarction in patients treated with thrombolysis.
AB  - The purpose of this study was to determine the prognostic value of thallium-201
      exercise treadmill testing performed early after myocardial infarction in
      patients treated with thrombolysis. A retrospectively identified group of 210
      patients treated with thrombolytic therapy alone (n = 131) or with thrombolytic
      therapy and coronary angioplasty (n = 79) who underwent tomographic thallium
      exercise treadmill testing 9 +/- 6 days after infarction were followed up for a
      median of 21 months. There was a high prevalence of abnormalities on the thallium
      studies. One hundred thirty-nine (66%) patients had a high-risk scan, defined as
      redistribution in at least one segment, a defect outside the infarct zone, or
      increased pulmonary uptake. Thirty-six (17%) patients underwent early
      revascularization. In the remaining 174 patients, there were 30 initial cardiac
      events (1 cardiac death, 11 nonfatal recurrent myocardial infarctions, and 18
      revascularization procedures performed > 3 months after the thallium study). No
      single exercise or thallium variable was predictive of outcome. At 2 years there
      were no differences in survival free of any cardiac event for patients with a
      high- or low-risk thallium scan treated with thrombolysis alone (high-risk scan
      86% and low-risk scan 80%; p not statistically significant [NS]) or with both
      thrombolysis and coronary angioplasty (high-risk scan 80% and low-risk scan 77%;
      p NS). Postinfarction exercise thallium variables associated with poor outcome in
      the prethrombolytic era were not associated with an adverse outcome in patients
      who had been treated with thrombolysis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7631606
TI  - Incremental value of exercise electrocardiography and thallium-201 testing in men
      and women for the presence and extent of coronary artery disease.
AB  - Our goal was to assess the incremental value of exercise testing in men and women
      for the diagnosis and extent of coronary artery disease. With data from one
      center, incremental logistic algorithms were developed and evaluated in a
      separate set of 865 patients from four centers. Variables included were pretest
      (age, sex, symptoms, diabetes, smoking, and cholesterol concentration); exercise
      electrocardiogram (ECG) (ST-segment depression [millimeters], ST-segment slope,
      peak heart rate, and change in systolic blood pressure); and thallium-201
      scintigram (defect presence, reversibility, and intensity of hypoperfusion). End
      points were coronary disease presence (50% diameter stenosis) and extent
      (multivessel disease). Accuracy and incremental value were assessed by receiver
      operating characteristic (ROC) curve analysis. Incremental ROC curve areas for
      disease presence were pretest 0.75 +/- 0.02, post-exercise ECG 0.82 +/- 0.01, and
      post-thallium scintigram 0.85 +/- 0.01 and for disease extent were pretest 0.71
      +/- 0.02, post-exercise ECG 0.76 +/- 0.02, and post-thallium scintigram 0.78 +/-
      0.02 (p < 0.005 for all increments). Incremental increases in accuracy were
      similar for men and women. We conclude that when multivariable algorithms derived
      from one center were applied to a separate group, there was a significant
      incremental increase in accuracy associated with exercise testing for the
      presence and extent of coronary disease. This increase in accuracy was similar
      for men and women.

PMID- 7631608
TI  - Predictors of mortality in patients with sustained ventricular tachycardias or
      ventricular fibrillation and depressed left ventricular function: importance of
      beta-blockade.
AB  - To study prognostic factors in patients with sustained ventricular tachycardias
      (VT) or ventricular fibrillation (VF) complicated by left ventricular
      dysfunction, we evaluated the predictive value of demographic, clinical, and
      hemodynamic parameters for cardiac mortality and sudden cardiac death in 85
      patients with VT or VF and left ventricular ejection fraction < 0.45 (mean 0.27
      +/- 0.10). Patients underwent serial drug testing and received appropriate
      antiarrhythmic treatment, with amiodarone given as last-resort therapy. During a
      follow-up of 24 +/- 13 months, 23 patients died of cardiac causes, and 18 of them
      died suddenly. Left ventricular ejection fraction < or = 0.27 and amiodarone
      treatment were related to greater cardiac mortality and increased risk of sudden
      cardiac death, whereas beta-blockade was associated with improved survival. In
      the multivariate model cardiac mortality was best predicted by a left ventricular
      ejection fraction < or = 0.27, and absence of beta-blockade and severe left
      ventricular dysfunction were the strongest predictors of sudden cardiac death. We
      conclude that severe left ventricular dysfunction predicts increased cardiac
      mortality and high risk of sudden cardiac death. Moreover, beta-blocking
      treatment is associated with lower cardiac mortality and a reduced risk of sudden
      cardiac death in patients with sustained VT or VF and depressed left ventricular
      function. beta-Blocking agents may therefore be an important addition to
      conventional antiarrhythmic treatment in patients with VT or VF and left
      ventricular dysfunction.

PMID- 7631607
TI  - Incidence of implantable defibrillator discharges after coronary
      revascularization in survivors of ischemic sudden cardiac death.
AB  - Coronary revascularization has been suggested as sole therapy for secondary
      prevention of sudden cardiac arrest associated with ischemia. The use of
      implantable defibrillators (ICD) in combination with coronary revascularization
      for this patient population is unclear. Among 412 consecutive patients receiving
      an ICD, 23 (6%) were identified as sudden cardiac arrest survivors who were
      noninducible with programmed stimulation and had unstable angina or ischemia on a
      functional study; they underwent successful coronary revascularization. During a
      follow-up of 34 +/- 18 months, 10 (43%) of the 23 patients received ICD shocks (8
      +/- 8 per patient, range 1 to 22 shocks), and nine of the 10 patients had
      syncope/presyncope associated with at least one ICD discharge. Patients with ICD
      discharges were compared with those without ICD discharges, and no clinical
      characteristics were statistically different between the two groups. In
      conclusion, revascularization alone may be inadequate therapy for survivors of
      sudden cardiac arrest associated with ischemia who are noninducible with
      programmed stimulation, and clinical variables cannot predict which patients are
      likely to have recurrent malignant ventricular arrhythmias.

PMID- 7631609
TI  - Role of transesophageal echocardiography in the detection of left atrial thrombus
      in patients with chronic nonrheumatic atrial fibrillation.
AB  - Transesophageal echocardiography was used to assess cardiac abnormalities
      associated with embolization in patients who had completed the Department of
      Veterans Affairs Cooperative Study of Stroke Prevention in Nonrheumatic Atrial
      Fibrillation at the Minneapolis and West Haven Department of Veterans Affairs
      Medical Centers without an embolic event. Patients were men, 71 +/- 7 years old,
      with atrial fibrillation of 6.2 +/- 4.3 years' duration who had received warfarin
      (n = 32) or placebo (n = 23) for 2 years. Thrombi were found in 5 of 55 patients
      (warfarin 4 and placebo 1; p = 0.39); spontaneous echo contrast was seen in 4 of
      5 patients. Other abnormalities identified included spontaneous echo contrast
      (47%), patent foramen ovale (54%), atrial septal aneurysm (7.3%), and left
      ventricular thrombus (3.6%). During 34 months of posttreatment follow-up, 5
      patients had a stroke (1 fatal), and 10 died. Potential sources of emboli did not
      predict subsequent outcome. Thus warfarin therapy did not preclude the presence
      of thrombi. Stroke reduction likely involves the prevention of emboli from
      sources in addition to the atrial appendage.

PMID- 7631610
TI  - Simultaneous invasive and noninvasive evaluations of baroreflex sensitivity with
      bolus phenylephrine technique.
AB  - Estimation of baroreflex sensitivity (BRS) is receiving increasing attention in
      clinical and experimental cardiology. Until recently, in most studies BRS has
      been assessed on the basis of invasive blood pressure measurement, which limits
      its use in large-scale studies and in clinical practice. The development of
      continuous noninvasive blood pressure monitoring has made it possible to assess
      BRS noninvasively. We compared central invasive and peripheral noninvasive
      techniques in the assessment of BRS during cardiac catheterization in 40 patients
      with possible coronary artery disease. The correlation between noninvasive and
      invasive BRS was high (r = 0.92; p < 0.001). However, the noninvasive method
      resulted in significantly higher BRS values than did the invasive method (7.1 +/-
      6.5 msec/mm Hg vs 5.1 +/- 4.3 msec/mm Hg, respectively; p < 0.001) because of the
      smaller increase in systolic blood pressure after phenylephrine injection by the
      noninvasive technique than by the invasive technique (18.9 +/- 6.8 mm Hg vs 25.2
      +/- 7.8 mm Hg, respectively; p < 0.01). The difference between noninvasive and
      invasive BRS correlated positively with invasive BRS (r = 0.54; p < 0.001) and
      inversely with age (r = -0.39; p < 0.01) and resting systolic blood pressure (r =
      -0.30, p < 0.05). A noninvasive BRS value of < 4.0 ms/mm Hg showed a sensitivity
      of 94%, a specificity of 91%, and an accuracy of 93% in identifying cases of
      reduced invasive BRS (< 3.0 msec/mm Hg). Our findings encourage the use of finger
      cuff method in the assessment of BRS. However, noninvasive BRS values were
      slightly but significantly higher than invasive BRS values, a difference that
      should be taken into account when BRS is measured by the noninvasive approach.

PMID- 7631611
TI  - Intracardiac ultrasonographic assessment of atrial septal defect area: in vitro
      validation and technical considerations.
AB  - Assessment of atrial septal defect (ASD) size and shape is important for planning
      and guiding its transcatheter occlusion and can potentially be achieved by
      intracardiac ultrasonography (ICUS). ICUS accuracy, however, must first be
      established against stable standards and technical imaging requirements defined.
      We therefore used 10, 20, and 30 MHz ICUS catheters to examine 17 ASDs that were
      0.16 to 6.7 cm2 in area and were surgically created in excised ovine hearts with
      10, 20, and 30 MHz ICUS catheters. ASD shape and area by ICUS were compared with
      direct video images of the actual ASD. In all instances minimal area by ICUS
      pullback agreed well with actual values (y = 1.04x + 0.2, SEE = 0.23 cm2, r =
      0.99) and corresponded well with defect shapes. The maximum angle between
      ultrasonography beam and septal plane allowing for complete ASD visualization was
      20 degrees. The angle depended on transducer frequency and septal thickness. This
      new technique has potential value for the accurate assessment of ASD shape and
      size and may be especially useful in the setting of transcatheter occlusion.

PMID- 7631612
TI  - Sudden death as a result of heart disease in morbid obesity.
AB  - Patients with morbid obesity have high rates of sudden, unexpected cardiac death.
      The mechanism of death in these patients is uncertain. Twenty-eight patients with
      morbid obesity (22 sudden cardiac deaths, 6 unnatural deaths) were compared to 11
      age-matched nonobese patients with traumatic deaths. Heart weight, left
      ventricular cavity diameter, left and right ventricular wall thickness,
      ventricular septal thickness, epicardial fat thickness, and extent of coronary
      artery atherosclerosis were determined; myocyte size, nuclear size, and degree of
      interstitial fibrosis were calculated morphometrically. Mean heart weights in the
      patients with morbid obesity were increased but remained constant as a percentage
      of body weight. Of the gross parameters, only heart weight and left ventricular
      cavity size were independent predictors of obesity. Of microscopic parameters,
      only nuclear area was an independent predictor of obesity. Of 22 patients with
      morbid obesity, dilated cardiomyopathy was the most frequent cause of sudden
      cardiac death in (10 patients), followed by severe coronary atherosclerosis (6),
      concentric left ventricular hypertrophy without left ventricular dilatation (4),
      pulmonary embolism (1), and hypoplastic coronary arteries (1). The cardiomyopathy
      of morbid obesity is characterized by cardiomegaly, left ventricular dilatation,
      and myocyte hypertrophy in the absence of interstitial fibrosis. It is the most
      common cause of sudden cardiac death in these patients.

PMID- 7631613
TI  - Hypotension during dobutamine stress echocardiography: is it related to dynamic
      intraventricular obstruction?
AB  - Although it has been shown that a hypotensive response during dobutamine stress
      echocardiography is not a marker of coronary artery disease, the mechanism of
      this response remains unclear. We hypothesize that hypotension during dobutamine
      stress echocardiography is not related to the development of dynamic
      intraventricular obstruction. The development of left ventricular outflow
      obstruction was defined as a late-peaking Doppler velocity profile that exceeded
      baseline outflow velocity by at least 1 m/sec in 104 consecutive patients
      undergoing dobutamine stress echocardiography. Left ventricular outflow
      obstruction was seen in 13% of 15 patients with a hypotensive response (group 1)
      and in 13% of 89 patients without a hypotensive response (group 2). The mean
      baseline systolic blood pressure was 157 +/- 21 mm Hg in group 1 compared to 139
      +/- 25 mm Hg in group 2 (p = 0.008). An ischemic response to dobutamine infusion
      as manifested by the development of new or worsening wall motion abnormalities
      was seen in 40% of group 1 patients and 34% of group 2 patients (p = 0.77). These
      data demonstrate that a hypotensive response is not related to the development of
      dynamic intraventricular obstruction during dobutamine stress echocardiography.
      Rather, there is a significant association between a higher baseline systolic
      blood pressure and a hypotensive response during dobutamine infusion.

PMID- 7631614
TI  - Familial sudden death syndrome with an abnormal signal-averaged electrocardiogram
      as a potential marker.
AB  - Most familial sudden cardiac death syndromes are associated with structural heart
      disease or 12-lead electrocardiographic abnormalities. Additionally, the utility
      of signal-averaged electrocardiograms in patients with familial sudden death
      syndromes has not been examined. We studied a kindred with sudden death to
      determine whether they could be classified into any of the previously described
      syndromes and whether an abnormal signal-averaged electrocardiogram is a marker
      for this trait. Surviving family members had normal 12-lead electrocardiograms
      and echocardiograms. Two of the patients who died from ventricular arrhythmias
      had normal hearts on autopsy. Two surviving family members had a clinical history
      of arrhythmic events; both had abnormal signal-averaged electrocardiograms and
      inducible ventricular arrhythmias during electrophysiologic studies. The other
      family members had normal signal-averaged electrocardiograms. This familial
      sudden death syndrome appears to be unique because the patients have anatomically
      normal hearts and normal 12-lead electrocardiograms. An abnormal signal-averaged
      electrocardiogram may be a marker for the sudden death trait.

PMID- 7631615
TI  - Conversion of atrial flutter in pediatric patients by transesophageal atrial
      pacing: a safe, effective, minimally invasive procedure.
AB  - Atrial reentry tachycardia, often termed atrial flutter, is an arrhythmia that is
      uncommon in the general pediatric population but is seen frequently in patients
      with congenital heart disease. One goal in treating the arrhythmia is to
      terminate it, returning the atrium to its underlying rhythm. This report
      describes the use of transesophageal atrial pacing to attempt termination of
      atrial reentry in 102 pediatric patients (158 episodes). The patients ranged in
      age from 1 hour to 41.5 years. Conversion was successful for 112 (71%) of 158
      episodes. Six of the 112 episodes required an infusion of procainamide after
      initial attempts at pacing led to atrial fibrillation. There were no significant
      differences between the ages of patients or the duration of the tachycardia in
      comparing successful versus unsuccessful conversions. In contrast, the atrial
      cycle lengths for the successfully converted tachycardias were significantly
      greater than for unsuccessful attempts. Transesophageal atrial pacing is a safe
      and effective means of terminating atrial flutter in the pediatric population. It
      is minimally invasive, it can often be performed in an outpatient setting, and
      the technique may occasionally be facilitated by infusion of intravenous
      procainamide.

PMID- 7631616
TI  - Mechanical complications after implantation of multiple-lead nonthoracotomy
      defibrillator systems: implications for management and future system design.
AB  - Nonthoracotomy lead system (NTL) implantable cardioverter defibrillators (ICDs)
      provide excellent protection against sudden death from ventricular
      tachyarrhythmias. However, these devices have unique mechanical complications and
      management issues. We reviewed the major complications occurring in 159 patients
      who underwent attempted implantation of a multilead NTL system. Successful
      implantation was obtained in 98% of patients. Two-year, all-cause actuarial
      survival on an intention-to-treat basis was 94%. Major complications occurred in
      28 (17.6%) patients over a follow-up period of 21 +/- 10 months. Complications
      included 11 (6.9%) lead dislodgements, 10 (5.7%) lead fractures in 9 patients, 2
      (1.3%) pocket infections, 1 frozen shoulder, 1 right ventricular perforation, 1
      pneumothorax, 1 bleed requiring transfusion, 1 thromboembolism, and 1 "twiddle"
      induced torsion of leads. Most of the lead dislodgements and fractures were
      identified by routine x-ray surveillance. Single-lead systems may significantly
      reduce complication rates in the future and maintain excellent survival rates.

PMID- 7631617
TI  - Clinical outcome of severe asymptomatic chronic aortic regurgitation: a long-term
      prospective follow-up study.
AB  - One hundred one patients with asymptomatic chronic severe aortic regurgitation
      and normal ejection fraction were monitored for up to 10 years (mean 55.4 +/-
      33.5 months). Predefined surgical indications were the development of cardiac
      symptoms or the documentation of impaired basal left ventricular function. During
      the follow-up period there were no cardiac deaths; 14 patients needed surgery, 8
      because of development of symptoms and 6 because of left ventricular impairment.
      The risk of surgery was 12% at 5 years and 24% at 10 years. Baseline end-systolic
      diameter > 50 mm and radionuclide ejection fraction < 60% were independent
      predictors or either cardiac symptoms or left ventricular dysfunction. In
      patients needing surgery, a pattern of progressive left ventricular dilatation
      was demonstrated. There were no deaths during surgery, and echocardiographic and
      radionuclide parameters normalized in the first year of follow-up. Our data
      confirm that the prognosis of severe aortic regurgitation in patients with no
      symptoms is good and that the occurrence of asymptomatic left ventricular
      dysfunction is an uncommon event. Surgery can be safely postponed until the
      appearance of cardiac symptoms or the documentation of left ventricular
      dysfunction at rest.

PMID- 7631618
TI  - Comparison of late outcome between Inoue balloon and double-balloon techniques
      for percutaneous mitral valvotomy in a matched study.
AB  - The follow-up results between Inoue balloon (n = 43, group 1) and double-balloon
      (n = 43, group 2) mitral valvotomies were compared in a patient-to-patient
      matched study. Matching was based on patients' age, mitral valve echo score,
      fluoroscopic calcification, mitral valve area before valvotomy, and follow-up
      period. The mean follow-up period was 13 +/- 9 months for both groups. At follow
      up, 72% of patients were symptom free in each group; 2 (4.7%) patients in group 1
      and 1 (2.3%) patient in group 2 underwent mitral valve replacement surgery. Of
      these 3 patients, 2 died after surgery, 1 from each group. The mitral valve area
      by Doppler was 1.8 +/- 0.3 cm2 in group 1 and 1.8 +/- 0.4 cm2 in group 2 (p =
      0.7); the area by echo planimetry was 1.7 +/- 0.3 cm2 in group 1 and 1.8 +/- 0.3
      cm2 in group 2 (p = 0.3) at follow-up. Restenosis occurred in 5 (12%) patients
      from each group. The cumulative restenosis-free rate was 96% at 1 years, 78% at 2
      years, and 58% at 3 years in group 1 and 98%, 76%, and 51%, respectively, in
      group 2 (p = 0.8). Balloon selection did not appear to influence the clinical
      outcome at follow-up. We conclude that both the inoue balloon and the double
      balloon valvotomies are effective therapies with comparable follow-up results for
      patients with mitral stenosis.

PMID- 7631619
TI  - Evolution of patients with clinical neurocardiogenic (vasovagal) syncope not
      subjected to specific treatment.
AB  - The purpose of this prospective study was to analyze the natural history of
      patients with clinical neurocardiogenic syncope. The results obtained with some
      therapeutic strategies in the prevention of neurocardiogenic syncope are
      encouraging. However, the benefit they represent when compared with the natural
      history of syncope has not been clearly established. Fifty-six consecutive
      patients with either (1) one or more episodes of syncope and a positive head-up
      tilt test or (2) typical history of vasovagal syncope despite a negative tilt
      test were monitored during a mean period of 16.1 +/- 10.2 months. Patients were
      discharged without any specific medication. There were no deaths during the
      follow-up period. Recurrences were found in 5 (8.9%) patients. The risk of
      recurrence was 7% after 1 year and 15% after 21 months. The prognosis of patients
      with clinical neurocardiogenic syncope is excellent as far as survival is
      concerned. Recurrences of episodes without specific treatment were uncommon after
      diagnosis had taken place. This finding strengthens the need to evaluate the
      effect of drugs with placebo control groups and to select the highest-risk group
      for treatment.

PMID- 7631620
TI  - Role of intracellular calcium in the antiarrhythmic effect of procainamide during
      ventricular fibrillation in rat hearts.
AB  - Increased intracellular calcium (calcium overload) is considered one of the
      factors that can initiate ventricular fibrillation. In addition, ventricular
      fibrillation itself can cause and possibly maintain calcium overload. The goal of
      this study was to determine whether the class IA antiarrhythmic agent
      procainamide can reduce calcium overload during ventricular fibrillation and, if
      so, whether this reduction could be responsible for the recovery of the left
      ventricular function after defibrillation. For this purpose, the effects of 0.1
      mmol/L of procainamide perfusion on left ventricular developed pressure, cardiac
      rate, and intracellular calcium during pacing-induced ventricular fibrillation
      were measured in isolated perfused rat hearts. Intracellular calcium was assessed
      by surface fluorometry after indo 1 loading. The concentration of procainamide
      was selected such that approximately half of the hearts would functionally
      recover from fibrillation. Cardiac rate and intracellular calcium were compared
      among four groups, depending on both the perfusate used and the recovery of left
      ventricular developed pressure at the end of the experiment. We found that
      procainamide reduced intracellular calcium to steady-state levels in hearts in
      which left ventricular function completely recovered (developed pressure > 67% of
      the steady-state value). However, intracellular calcium remained elevated in
      partially recovered hearts (33% < or = pressure < or = 67%) and in nonrecovered
      hearts (pressure < 33%). Thus procainamide can reduce calcium overload during
      ventricular fibrillation, and this reduction could be responsible for the
      recovery of left ventricular function after defibrillation. This reduction was
      use dependent, that is, dependent on high cardiac rates during fibrillation
      rather than on the decrease of cardiac rates before or during defibrillation.

PMID- 7631623
TI  - Dipyridamole-thallium versus dobutamine echocardiographic stress testing: a
      clinician's viewpoint.

PMID- 7631621
TI  - Low-dose drug combination therapy: an alternative first-line approach to
      hypertension treatment.
AB  - To investigate the concept that the initial treatment of hypertension with low
      doses of two antihypertensives that have different modes of action and additive
      effects may achieve control of blood pressure and minimize the dose-dependent
      adverse effects seen with conventional monotherapy, a randomized, double-blind
      parallel group dose-escalation study was conducted. After a 4 to 5 week placebo
      washout period, 218 men and women with diastolic blood pressure between 95 and
      114 mm Hg were randomly allocated to take: amlodipine (2.5 to 10 mg), enalapril
      (5 to 20 mg), and the low-dose combination of bisoprolol (2.5 to 10 mg) with 6.25
      mg of hydrochlorothiazide (HCTZ). All drugs were administered once daily,
      titrated to optimal response, and taken for a total of 12 weeks. Blood pressure
      was measured 24 hours after dose. The response rates (either a diastolic blood
      pressure < or = 90 mm Hg or a decrease of diastolic pressure > or = 10 mm Hg)
      were 71% for bisoprolol-6.25 mg HCTZ, 69% for amlodipine, and 45% for enalapril.
      The mean decreases in systolic/diastolic blood pressure from baseline were
      13.4/10.7, 12.8/10.2, and 7.3/6.6 mm Hg for bisoprolol-6.25 mg HCTZ, amlodipine,
      and enalapril, respectively. The mean change with enalapril was less than the
      other drugs (p < 0.01), although the once-daily dosing of enalapril and the
      maximum dose of 20 mg might not have been optimal for this agent.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7631622
TI  - Implications of increased lung thallium uptake during exercise single photon
      emission computed tomography imaging.
AB  - Increased lung thallium uptake during exercise is an important marker of patients
      who are at high risk and have CAD; however, most previous studies were done with
      planar imaging, and therefore it is unclear whether this conclusion is also true
      with SPECT imaging. This study examined the lung thallium uptake during exercise
      SPECT imaging in 1031 patients who also underwent coronary angiography. The lung
      thallium uptake was increased in 309 patients (group 1) and normal in 722
      patients (group 2). Compared with patients in group 2, those in group 1 had more
      ST segment depression (44% vs 28%, p = 0.01), previous Q-wave myocardial
      infarction (28% vs 17%, p = 0.0001), larger perfusion defects (24% +/- 11% vs 10%
      +/- 11%, p = 0.0001), and multivessel CAD by angiography (75% vs 47%, p =
      0.0001). Multivariate discriminant analysis identified left ventricular dilation,
      reversible defects, the size of perfusion abnormality, and the extent of CAD as
      independent predictors of increased lung thallium uptake. Increased lung thallium
      uptake was more common in men than women regardless of the extent of CAD: 26%
      versus 11% in patients with one-vessel, 38% versus 18% in patients with two
      vessel, and 51% versus 31% in patients with three-vessel disease (p < 0.001
      each). Thus increased lung thallium uptake by SPECT identifies patients with more
      severe anatomic and functional evidence of CAD. The sex-related difference
      suggests the need for a sex-specific normal file for quantitative analysis.

PMID- 7631624
TI  - Value and limitations of intravascular ultrasound imaging in characterizing
      coronary atherosclerotic plaque.
AB  - Intravascular ultrasound uses a high-frequency, miniaturized, ultrasound
      transducer positioned on the tip of a coronary catheter to provide detailed cross
      sectional images of the coronary vessel wall. Unlike angiography, which details
      only luminal encroachment, this imaging technique has the unique potential to
      provide an image of the atherosclerotic plaque, characterize its composition, and
      assess stenosis severity. Lipid-filled "soft" plaque, dense fibrous "hard"
      plaque, calcification, and thrombosis have all been identified on intravascular
      ultrasound images. Individual lesion types have been associated with specific
      clinical ischemic syndromes and with different responses to catheter-based
      intervention. By means of analyzing tissue composition, intravascular ultrasound
      may permit identification of high-risk lesions that may eventually rupture and
      cause unstable coronary ischemic syndromes. This article reviews the current
      approaches to plaque characterization by two-dimensional intravascular ultrasound
      imaging and addresses clinical implications, technical limitations, and future
      promise of the technique.

PMID- 7631625
TI  - Potential for contamination of transesophageal echocardiographic scopes by
      radionuclides from patients undergoing nuclear imaging studies.

PMID- 7631626
TI  - Pulmonary artery hypertension in chronic intravenous cocaine users.

PMID- 7631628
TI  - Transesophageal echocardiography in infective endocarditis: the standard for the
      1990s?

PMID- 7631627
TI  - Bradycardia-facilitated polymorphic ventricular tachycardia caused by amiodarone
      after radiofrequency modification of atrioventricular conduction.

PMID- 7631629
TI  - Observations on a mumps epidemic in a "virgin" population. 1958.

PMID- 7631630
TI  - Coronary heart disease prevalence and its relation to risk factors in American
      Indians. The Strong Heart Study.
AB  - Although coronary heart disease (CHD) is currently the leading cause of death
      among American Indians, information on the prevalence of CHD and its association
      with known cardiovascular risk factors is limited. The Strong Heart Study was
      initiated in 1988 to quantify cardiovascular disease and its risk factors among
      three geographically diverse groups of American Indians. Members of 13 Indian
      communities in Arizona, Oklahoma, and South and North Dakota between 45 and 74
      years of age underwent a physical examination that included medical history; an
      electrocardiogram; anthropometric and blood pressure measurements; an oral
      glucose tolerance test; and measurements of fasting plasma lipoproteins,
      fibrinogen, insulin, hemoglobin A1c, and urinary albumin. Prevalence rates of
      definite myocardial infarction and definite CHD were higher in men than in women
      at all three centers (p < 0.0001) and higher in those with diabetes mellitus (p =
      0.002 in men and p = 0.0003 in women). Diabetes was associated with relatively
      higher prevalence rates of myocardial infarction (diabetic:nondiabetic prevalence
      ratio = 3.8 vs. 1.9) and CHD (prevalence ratio = 4.6 vs. 1.8) in women than in
      men. Prevalence rates of heart disease were lowest in the communities in Arizona;
      prevalence rates were similar in Oklahoma and South Dakota/North Dakota and were
      two- to threefold higher than those in Arizona. By logistic regression, prevalent
      CHD among American Indians was significantly and independently related to age,
      diabetes, hypertension, albuminuria, percentage of body fat, smoking, high
      concentrations of plasma insulin, and low concentrations of high density
      lipoprotein cholesterol. In contrast to reports from other non-Indian
      populations, diabetes was the strongest risk factor. The lower prevalence of CHD
      among Indians in Arizona is distinctive in view of their higher rates of
      diabetes, obesity, hypertension, and albuminuria, but it may be partly related to
      their low frequency of smoking and their low concentrations of total and low
      density lipoprotein cholesterol. These findings from the initial Strong Heart
      Study examination emphasize the importance of diabetes and its associated
      variables as risk factors for CHD in Native American populations.

PMID- 7631631
TI  - Cardiovascular disease risk factors among American Indians. The Strong Heart
      Study.
AB  - The Strong Heart Study, a study of cardiovascular disease among American Indians,
      was conducted to determine cardiovascular disease rates and the prevalence of
      risk factors among members of 13 tribal groups in South Dakota/North Dakota
      (SD/ND), southeastern Oklahoma, and Arizona. From 1989 to 1992, 4,549 tribal
      members aged 45-74 years (62% of eligible participants) were surveyed and
      examined for cardiovascular disease and its risk factors. Mean total cholesterol
      concentrations were over 20 mg/dl lower among the men and 27 mg/dl lower among
      the women than national mean levels for the same age groups. Cholesterol levels
      varied by tribal group; Arizona Indians had mean levels more than 20 mg/dl lower
      than those of SD/ND Indians. The prevalence of hypercholesterolemia was almost
      twice as high among SD/ND Indians as among Arizona Indians, but the rates for all
      three groups were much lower than total US rates (all races). Mean levels of high
      density lipoprotein cholesterol were lower among Indian men and women than in the
      US population as a whole. The prevalence of hypertension among Arizona and
      Oklahoma Indians was higher than that for the entire United States. SD/ND Indians
      had significantly lower mean blood pressures and prevalence rates of hypertension
      than Oklahoma and Arizona Indians and the United States as a whole. The
      prevalence of cigarette smoking was higher for all Indian groups except Arizona
      women in comparison with US rates. Smoking rates were highest in SD/ND and lowest
      in Arizona. Indian smokers smoked fewer cigarettes per day than the average US
      smoker. Arizona Indians had the highest prevalence of diabetes mellitus; over 60%
      of those participants were diabetic. In Oklahoma and SD/ND, one third of the men
      and over 40% of the women were diabetic. In addition, 13-20% of the participants
      had impaired glucose tolerance. Proteinuria was also a common problem; almost
      half of the Arizona Indians had micro- or macroalbuminuria, and 20% of Oklahoma
      and SD/ND Indians had significant proteinuria. The prevalence of obesity was high
      in all three groups, with Arizona Indians having the highest rates and the
      highest mean body mass indices. The prevalence of current alcohol use was lower
      among Indians than in the nation as a whole, but binge drinking was common among
      those who used alcohol. These results indicate that cardiovascular disease risk
      factors vary significantly among tribal groups. Prevention programs tailored
      toward decreasing the prevalence of risk factors are recommended for long-term
      reduction of cardiovascular disease rates in American Indian communities.

PMID- 7631632
TI  - Uric acid and coronary heart disease risk: evidence for a role of uric acid in
      the obesity-insulin resistance syndrome. The Normative Aging Study.
AB  - Various epidemiologic studies have linked an increase in serum uric acid level to
      an increased risk of coronary heart disease. The reasons for this finding are
      unclear. The authors examined the influence of a number of cardiovascular disease
      risk factors on serum uric acid level in 886 middle-aged and older men
      participating in the Normative Aging Study. The men were examined between 1987
      and 1991. In a multivariate regression model predicting serum uric acid level,
      uric acid was positively associated with body mass index (weight (kg)/height (m)2
      beta = 0.041 mg/dl per kg/m2, p = 0.003), abdomen: hip circumference ratio (beta
      = 1.88 mg/dl per cm/cm, p = 0.048), log alcohol intake (beta = 0.150 mg/dl per
      g/week, p = 0.0001), and log postcarbohydrate insulin level (beta = 0.157 mg/dl
      per log(microIU/ml), p = 0.005). Serum uric acid level was negatively associated
      with age (beta = -0.012 mg/dl per year of age, p = 0.017) and log physical
      activity (beta = -0.152 mg/dl per kcal/week, p = 0.0001). The data suggest that
      serum uric acid may be involved in the obesity-insulin resistance syndrome, which
      in turn may explain the relation of serum uric acid to coronary atherosclerosis.

PMID- 7631633
TI  - The contribution of urinary cations to the blood pressure differences associated
      with migration.
AB  - People living in unacculturated societies have a low average blood pressure and
      little rise in blood pressure with age. In a community-based survey in
      southwestern China, the authors assessed the contribution of urinary cation
      excretion to differences in blood pressure between an unacculturated group (Yi
      farmers) and migrants to an urban environment, as well as urban controls from a
      different ethnic group (Han). In March 1989, blood pressure and overnight urinary
      electrolyte levels were measured on 3 consecutive days in 313 Yi farmers, 265 Yi
      migrants, and 253 urban Han residents, all male. Of the urinary electrolytes, a
      higher sodium:potassium ratio best explained the higher blood pressure in the
      migrants. Yi farmers had lower systolic (106.7 mmHg vs. 114.8 mmHg, respectively)
      and diastolic (66.2 mmHg vs. 71.3 mmHg, respectively) blood pressures than Yi
      migrants. However, even after adjustment for age, body mass index, alcohol
      intake, and urinary sodium, potassium, calcium, and magnesium excretion, Yi
      farmers continued to have lower average blood pressures than Yi migrants. In
      pooled analyses of all three groups, urinary sodium and calcium were positively
      related and urinary potassium and magnesium were inversely related to blood
      pressure. Migration is associated with a higher blood pressure that is only
      partially explained by higher levels of adiposity and alcohol and sodium intake
      and lower levels of potassium and magnesium intake.

PMID- 7631634
TI  - Prognostic factors for all-cause mortality among hemophiliacs infected with human
      immunodeficiency virus.
AB  - To identify the prognostic significance of hemophilia- and virus-related factors,
      the authors undertook a survival analysis among 644 human immunodeficiency virus
      (HIV)-infected subjects enrolled in the Multicenter Hemophilia Cohort Study
      between 1985 and 1993. Acquired immunodeficiency syndrome (AIDS) was the leading
      cause of death, followed by hemorrhage and hepatic disease. Adverse prognostic
      factors included older age and CD4-positive lymphocyte values below 14 percent
      either at entry (age-adjusted mortality rate ratio (RR) = 6.4, 95% confidence
      interval (CI) 3.4-12.1) or after entry (time-dependent RR = 4.2, 95% CI 2.6-6.7);
      indeterminate antibody responses to hepatitis C virus (RR = 3.0, 95% CI 1.8-5.0);
      and inhibitory antibodies to factor VIII concentrates (RR = 1.8, 95% CI 1.1-3.1).
      Indeterminate hepatitis C virus status was associated with mortality from hepatic
      disease but not with AIDS mortality. Factors that were not prognostic included
      duration of HIV infection, hepatitis B virus infection, and other hemophilia
      variables. These findings suggest that fatal liver disease among coinfected
      subjects with an indeterminate hepatitis C virus status is probably related to an
      insufficient humoral response secondary to HIV immune dysfunction and that the
      risk of death among HIV-infected subjects is best evaluated with age and duration
      of low CD4 percentage.

PMID- 7631635
TI  - Temporal trends in human immunodeficiency virus seroprevalence and sexual
      behavior at the San Francisco municipal sexually transmitted disease clinic, 1989
      1992.
AB  - The authors analyzed temporal trends in human immunodeficiency virus (HIV)
      infection among men and women who visited the San Francisco municipal sexually
      transmitted disease clinic between 1989 and 1992, using blinded HIV
      seroprevalence data. Temporal changes in sexual behavior were evaluated by
      abstracting self-reported information on sexual behaviors from a random sample of
      charts of men who visited the clinic between 1990 and 1992. From 1989 to 1992,
      HIV seropositivity declined from 2.0% to 1.0% among women (p = 0.06) and from
      18.9% to 12.0% (p < 0.001) among men. The percentage of patients who reported
      having anal intercourse in the previous year did not change significantly during
      the study period. The percentage of male patients who reported having vaginal
      intercourse during the previous year decreased from 82.9% to 78.6% (p < 0.05),
      and the percentage of male patients who reported engaging in receptive oral sex
      during the previous year increased from 24.0% to 41.6% (p < 0.001). The
      percentage of male patients who reported that they always used condoms increased
      from 31.8% to 49.2% for anal sex, from 8.7% to 19.5% for vaginal sex, and from
      1.4% to 6.3% for oral sex (p < 0.05). Among patients visiting the sexually
      transmitted disease clinic, there was a steady and significant decline in HIV
      seroprevalence. The decline in HIV seroprevalence was accompanied by a
      significant trend toward safer sexual practices. However, by the end of the study
      period, less than half of the patients reported using condoms all of the time,
      which suggests that there is a need to expand behavioral interventions to focus
      on high-risk persons.

PMID- 7631636
TI  - The Multicenter AIDS Cohort Study: retention after 9 1/2 years.
AB  - In a longitudinal, multicenter study of 4,954 men at risk for human
      immunodeficiency virus infection and acquired immunodeficiency syndrome, data
      from the first 9.5 years of follow-up (April 1984 through September 1993) were
      used to determine differences between those who remained in the study and those
      who dropped out. Demographic variables (age, race, education, employment, and
      study center), health status (human immunodeficiency virus type 1 serostatus and
      depression), and behavioral characteristics (alcohol drinking, drug use, and anal
      receptive intercourse) were analyzed. Strategies for promoting retention included
      having frequent contact with participants, generating trust, keeping participants
      well-informed, utilizing multiple resources for follow-up, and providing flexible
      methods of participation. After 9.5 years of follow-up, vital status was known
      for 4,385 (88.5%) of the participants. Results from multiple logistic regression
      showed that race, age, education, and smoking were each significantly associated
      with nonparticipation (p < 0.001). A high level of retention was maintained in
      this well-educated and highly motivated cohort of homosexual/bisexual men.
      Extensive follow-up methods may improve case-finding. Nonwhite race, younger age,
      less education, and smoking were important predictors of dropping out. These
      findings identify specific groups for targeting follow-up efforts to reduce
      potential bias due to dropout.

PMID- 7631637
TI  - Seroepidemiology of hepatitis B virus in a population of injecting drug users.
      Association with drug injection patterns.
AB  - To investigate the epidemiology of hepatitis B virus (HBV) infection among
      injecting drug users, the authors assessed the prevalence of HBV seromarkers
      among 2,558 injecting drug users recruited through street outreach in Baltimore,
      Maryland, in 1988-1989. Eighty percent of the drug users had at least one HBV
      seromarker. HBV seropositivity was associated with increasing age, duration of
      injecting drug use, African-American ethnicity, injecting drugs at least once
      daily, and sharing needles or visiting "shooting galleries" during the previous
      11 years, but not with high-risk sexual behaviors or a history of sexually
      transmitted disease. This finding is possibly due to the relative inefficiency of
      sexual transmission as compared with parenteral transmission in injecting drug
      users. In addition, HBV seropositivity was strongly associated with
      seropositivity for hepatitis C virus and human immunodeficiency virus. The
      authors conclude that HBV transmission among injecting drug users occurs
      primarily through the sharing of contaminated drug injecting equipment rather
      than through sexual relations, and that efforts to prevent HBV infection must
      target injecting drug users early in their injecting careers.

PMID- 7631638
TI  - Misclassification of nutrient and energy intake from use of closed-ended
      questions in epidemiologic research.
AB  - The authors investigated the effect of collecting food frequency intake data
      using questionnaires that record response intervals rather than exact frequencies
      of consumption. Measures of energy and 24 nutrients were calculated using both
      types of frequency data for subjects' mean intakes, rank classifications and
      group mean values. Frequency data obtained between 1987 and 1989 using the open
      ended Health Habits and History Questionnaire (HHHQ) developed by Block and
      associates at the National Cancer Institute were recoded into the interval
      response formats used by the computer-scannable version of the HHHQ and into the
      format used in the food frequency questionnaire developed by Willett for the
      Nurses' Health Study and other studies. Compared with the open-ended HHHQ, for
      otherwise identical data sets, the closed-ended HHHQ and Willett response
      categories produced significantly different (p < 0.05) measures of intake on the
      individual level for 18 (72%) (HHHQ) and 16 (64%) (Willett) of the 25 nutrient
      and energy measures studied, and they ranked 13-53% (HHHQ) and 16-52% (Willett)
      of subjects in different quintiles for the various measures. Use of food
      frequency questionnaires with closed-ended response categories causes
      nondifferential misclassification that could bias study results. To reduce such
      misclassification in epidemiologic studies, the authors recommend that food
      frequency questionnaires obtain exact frequencies of intake for measurement of
      diet exposure, and they describe an open-ended questionnaire layout which does so
      and also permits computer scanning of data.

PMID- 7631640
TI  - Computer simulation analysis of Sartwell's incubation period model for diseases
      with uncertain etiology. The effect of competing risk.
AB  - Computer simulation was applied to Sartwell's model to examine the impact of
      competing risks of death on the underlying assumptions and the power to reject
      both uniform and normal incubation period distributions. Exponential and
      nonparametric survival functions were imposed onto lognormal, uniform, and normal
      distributions to create random samples reflecting competing risk. These random
      samples were evaluated with the Shapiro-Wilk's test to determine the proportion
      for which the lognormal distribution was rejected. The simulations indicated that
      competing causes of death do not significantly alter the lognormal distribution
      of incubation periods. In only approximately 5% of the samples drawn from a
      lognormal distribution was a lognormal hypothesis rejected with a goodness-of-fit
      test when sample size varied from 20 to 500. There was generally good power (>
      80%) to reject a lognormal distribution if the random samples were generated from
      a uniform distribution of incubation times, but not when they were generated from
      a normal distribution, particularly with increasing ages at disease onset.
      Varying the standard deviation did not significantly change the simulation
      results if the random samples came from a lognormal or uniform distribution.
      These conclusions were further supported by application of Sartwell's model to
      published data on the ages of onset for several chronic diseases.

PMID- 7631639
TI  - Cost-efficient design of a diet validation study.
AB  - Validation studies of food frequency questionnaires (FFQs) describe the extent to
      which the FFQ reflects true diet and the relation between measured and true diet
      (calibration). Calibration data can be used to estimate the relation between
      disease and diet that would have been observed in the absence of error due to the
      FFQ. In this paper, the authors consider the optimal design of a validation study
      when the goal is precise calibration of an FFQ. The authors posed the following
      question: Under the constraint of a fixed total cost for a validation study, what
      is the optimal choice of number of subjects (n) and number of days (m) of diet
      records (or 24-hour recalls) per subject? The optimal n and m were found to
      depend upon 1) the ratio between the costs of the initial and subsequent 1-day
      diet records and 2) the ratio of the variance in day-to-day nutrient intake to
      the variance in true diet for a fixed FFQ value. Data for the two ratios and
      optimal values of n and m are given under a variety of realistic scenarios. The
      authors conclude that in most settings the optimal study design will rarely
      require more than four or five 1-day diet records per subject.

PMID- 7631643
TI  - Hypoparathyroidism counteracts risk factors for osteoporosis.
AB  - Although increased bone density has been reported in patients with
      hypoparathyroidism, it is not known whether hypoparathyroidism can overcome the
      influence of risk factors for osteoporosis and whether the increased bone density
      is uniform throughout the entire skeleton or greater in certain regions depending
      on the bone composition and location. In the current study, bone density was
      measured in patients with postsurgical hypoparathyroidism and risk factors for
      osteoporosis. Bone mineral density was determined in eight patients with
      postsurgical hypoparathyroidism, one with idiopathic hypoparathyroidism, and two
      with pseudohypoparathyroidism in eight different areas of the skeleton using well
      established methods: single photon absorptiometry of the radius, dual energy x
      ray absorptiometry of the spine, hip, and the whole skeleton, and quantitative
      computed tomography of the spine. Risk factors for osteoporosis were documented
      in each subject. The data showed that despite the presence of 1-4 risk factors
      for osteoporosis, patients with postsurgical hypoparathyroidism had bone mineral
      density above the normal mean in most locations. The locations with the highest
      increment were the Ward's triangle and the trochanter area of the proximal femur
      (dual energy x-ray absorptiometry) (Ward's: Z score + 1.59 +/- 0.57, P < 0.03;
      trochanter 1.31 +/- 0.42, P < 0.02). The elevation of bone density was not
      observed in one patient with idiopathic hypoparathyroidism, and variable results
      were observed in two patients with pseudohypoparathyroidism. Based on these
      findings, in postsurgical hypoparathyroidism, the bone mineral density is above
      the normal mean despite the presence of risk factors for osteoporosis, and both
      cortical and trabecular bone are affected.

PMID- 7631641
TI  - Pretreatment with 1,25(OH)2D3 protects from Cytoxan-induced alopecia without
      protecting the leukemic cells from Cytoxan.
AB  - The authors previously demonstrated that pretreatment with 1,25(OH)2D3 protects
      from Cytoxan-induced alopecia in the rat model. The current study was designed to
      investigate whether 1,25(OH)2D3 protects the transplantable rat chloroleukemia
      (C51) cells from the cytotoxic effects of Cytoxan. In vitro, 4
      hydroperoxycyclophosphamide had a dose-dependent cytotoxic effect on C51 cells.
      In separate experiments, preincubation with 1,25(OH)2D3 did not protect the C51
      cells from the cytotoxic effects of 4-hydroperoxycyclophosphamide. In vivo, 4
      groups of 10 5-day-old rats were treated as follows: Groups 1 and 2 received 0.2
      micrograms of 1,25(OH)2D3 topically in ethanol daily starting on day 5 through
      day 10. Groups 3 and 4 received ethanol topically similarly. On day 7, all rats
      received 1 x 10(5) C51 cells intraperitoneally. On day 11, groups 1 and 3
      received 35 mg/kg Cytoxan intraperitoneally. All rats in groups 2 and 4 were dead
      of leukemia by day 34. In groups 1 and 3, only 1 of 10 and 2 of 10 rats died of
      leukemia, respectively. Alopecia developed in all rats in group 3. In contrast,
      all rats in group 1 were protected from Cytoxan-induced alopecia. These results
      indicate that, in vivo, pretreatment with 1,25(OH)2D3 does not protect the rat
      chloroleukemia cells from the cytotoxic effect of Cytoxan, while protecting from
      Cytoxan-induced alopecia.

PMID- 7631642
TI  - Altered metabolism and mortality in patients with colon cancer receiving
      chemotherapy.
AB  - To identify the metabolic effects of 5-fluorouracil and hydrazine sulfate
      therapy, 22 patients with colon cancer were admitted prospectively to a Clinical
      Research Center for serial measurement of counter-regulatory hormones, fasting
      hepatic glucose production (HGP), intravenous glucose tolerance test, plasma
      leucine appearance (LA) and leucine oxidation. Combined therapy was associated
      with a significant reduction in fasting glucose level (98 +/- 2 mg/dL to 94 +/-
      2, P < 0.025) without a significant fall in fasting HGP (2.09 +/- 0.11 mg/kg/min
      versus 2.03 +/- 0.13; P > 0.05). The decreased fasting glucose value was
      associated with a mild but not statistically improved glucose disposal rate in
      response to the intravenous glucose tolerance test (1.34 +/- 0.07 %/min vs 1.47
      +/- 0.11, P = 0.15). Plasma leucine appearance was significantly reduced after 2
      months of therapy (63.3 +/- 3.0 mumol/kg/hr vs 57.1 +/- 3.9 mumol/kg/hr; P <
      0.025), but leucine oxidation (11.5 +/- 1.1 mumol/kg/hr vs 11.2 +/- 1.1
      mumol/kg/hr) was not altered. Despite the fact that plasma triiodothyronine
      concentrations significantly increased with therapy, it was not associated with
      plasma LA. Half of the patients with cancer died 14 +/- 4 months after the study,
      and the other half were alive 58 +/- 2 months later. Survival time can be
      estimated with 59% accuracy using plasma LA, HGP, carcino-embryonic antigen, and
      insulin concentration. Multiple regression analysis identified that plasma LA was
      related directly to length of survival time, and baseline HGP, carcino-embryonic
      antigen, and insulin concentration were related inversely to length of
      survival.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7631646
TI  - Pituitary apoplexy into nonadenomatous tissue: case report and review.
AB  - Pituitary apoplexy into nonadenomatous tissue is extremely rare. The authors
      describe a 20-year-old woman with symptomatic pituitary hemorrhage into an
      apparently intrasellar malignant teratoma, which caused headache, visual
      impairment, involvement of III, IV, VI, and 1st division of the V cranial nerves,
      and hypopituitarism. Diabetes insipidus had developed previously. Magnetic
      resonance scans had a high-intensity signal in the pituitary on T1- and T2
      weighted images, and lack of the signal of the posterior pituitary.
      Transsphenoidal approach, radiotherapy, and chemotherapy management did not
      preclude a fatal outcome.

PMID- 7631644
TI  - Effects of cocaine on cortisol secretion in humans.
AB  - The effects of acute cocaine administration on the pituitary adrenal axis in
      humans without a history of drug abuse are unknown. The authors studied 12 male
      volunteers twice in a double-blinded, placebo-controlled, randomized fashion.
      After intranasal administration of 2 mg/kg cocaine, cortisol levels were
      significantly higher than after placebo administration. The authors concluded
      that acute administration of cocaine to humans increases cortisol secretion.

PMID- 7631645
TI  - Case report: Langerhans cell histiocytosis associated with elevation of
      angiotensin-converting enzyme levels.
AB  - The authors describe a 22-year-old man with osteolytic mandibular and maxillary
      lesions. Biopsy substantiated the presence of Langerhans cell histiocytosis
      (eosinophilic granuloma). Levels of serum angiotensin-converting enzyme (ACE)
      were elevated repeatedly. After definitive therapy with excision and bone
      grafting, ACE levels returned to normal. The role of histiocytes in ACE
      production is discussed. Langerhans cell histiocytosis should be considered in
      the diagnosis of conditions occurring with elevation of serum ACE levels and
      clinical findings similar to sarcoidosis.

PMID- 7631647
TI  - Case report: vitamin D-mediated hypercalcemia in fungal infections.
AB  - Hypercalcemia has been well described in a variety of neoplastic and
      granulomatous diseases. One mechanism for this hypercalcemia is via the excess
      production of 1,25-dihydroxyvitamin D from extra-renal sources. The authors
      describe an AIDS patient infected with Cryptococcus neoformans who had suggestive
      evidence of vitamin D-mediated hypercalcemia. He had an elevated serum 1,25
      dihydroxyvitamin D value, a normal 25-hydroxyvitamin D value, and low values for
      parathyroid hormone and parathyroid hormone-related peptide. Most previously
      reported cases of hypercalcemia associated with fungal infections did not include
      sufficient evidence to implicate a role for excess 1,25-dihydroxyvitamin D
      production, except for two case reports involving patients with hypercalcemia
      with infections due to Pneumocystis carinii and Candida albicans. The authors'
      patient's hypercalcemia resolved during treatment of his underlying infection.
      Patients with hypercalcemia or in whom hypercalcemia develops during a
      disseminated fungal infection should have vitamin D metabolites measured as part
      of their work-up.

PMID- 7631648
TI  - Southwestern Internal Medicine Conference: prevention of hip fractures in the
      elderly.
AB  - Hip fracture is a common, morbid, and costly health problem. Because our
      population is aging, hip fractures will remain a major health concern as we enter
      the next century. It has been estimated that by the year 2040, 512,000 hip
      fractures will occur annually in people 50 years or older. A number of factors
      common in the elderly increase the risk of falling. Falls and age-related changes
      that influence bone quality increase susceptibility to fracture. In this article,
      the author focuses on studies that identified risk factors and strategies to
      reduce falls as well as pharmacologic agents that may reduce fracture risk.
      Because of the multifactorial etiology of hip fractures, their prevention will
      ultimately require a combination of pharmacologic approaches to improve bone
      strength and strategies to prevent falls and limit injury.

PMID- 7631649
TI  - Adverse effects of NSAIDs.

PMID- 7631650
TI  - Jail won't cure addiction.

PMID- 7631651
TI  - Jail won't cure addiction.

PMID- 7631653
TI  - Helping the alcoholic patient recover.
AB  - The patient may come to your unit because of any of the numerous possible health
      consequences of alcoholism. Or his dependence may surface after he's admitted for
      some unrelated problem. In either case, your challenge is to see him through
      withdrawal and set him on the path to long-term recovery.

PMID- 7631652
TI  - EMLA's safety for small infants.

PMID- 7631654
TI  - What's in a name?

PMID- 7631655
TI  - How to protect the dysphagic stroke patient.

PMID- 7631656
TI  - AJN interview. Sandy Ritz. Interview by Marietta Lee.

PMID- 7631657
TI  - Clinical snapshot: adult respiratory distress syndrome.

PMID- 7631658
TI  - What you need to know about corticosteroid therapy.

PMID- 7631659
TI  - Emergency! Status epilepticus.

PMID- 7631660
TI  - The right to refuse treatment.

PMID- 7631661
TI  - APNs: pioneers in patient care.

PMID- 7631662
TI  - Deciding on hormone replacement therapy.

PMID- 7631663
TI  - Expanding paradigms of self-care.

PMID- 7631664
TI  - Crossing the black ocean. For many AIDS patients, the journey toward death is too
      long.

PMID- 7631665
TI  - Fetal venous, intracardiac, and arterial blood flow measurements in intrauterine
      growth retardation: relationship with fetal blood gases.
AB  - OBJECTIVE: Our purpose was to investigate arterial, venous, and intracardiac
      blood flow in growth-retarded fetuses and to relate the Doppler results to blood
      gases in umbilical venous blood obtained by cordocentesis. STUDY DESIGN: A cross
      sectional, pulsed-wave color Doppler ultrasonographic study of 23 severely growth
      retarded fetuses undergoing cordocentesis and measurement of blood gases was
      performed. Blood velocity waveforms were recorded from the descending thoracic
      aorta, middle cerebral artery, inferior vena cava, ductus venosus, and
      atrioventricular valves. RESULTS: The Doppler studies demonstrated evidence of
      redistribution in the arterial system with increased impedance to flow in the
      aorta and decreased impedance in the cerebral circulation. The velocity of flow
      in the venous system and across the atrioventricular valves was decreased,
      whereas pulsatility of waveforms in the inferior vena cava and ductus venosus was
      increased. The mean umbilical venous blood PO2 and pH were decreased, and there
      were significant associations between blood gases and Doppler parameters in the
      thoracic aorta, middle cerebral artery, and ductus venosus. CONCLUSION: In severe
      intrauterine growth retardation the degree of fetal acidemia can be estimated
      from Doppler measurements of pulsatility in both the arterial system and the
      ductus venosus.

PMID- 7631666
TI  - Laparoscopic bilateral pelvic and paraaortic lymph node sampling: an evolving
      technique.
AB  - OBJECTIVE: Reports describing laparoscopic lymph node sampling in patients with
      gynecologic malignancies have yet to describe a method to sample left-sided
      aortic lymph nodes that has been successful in a large series of patients. We
      submit our experience with evolving techniques that allow for excellent
      visualization and resection of both left and right aortic and pelvic lymph nodes.
      STUDY DESIGN: Forty patients with gynecologic malignancies underwent laparoscopy
      for surgical staging. Thirty-five of the patients were completely staged
      laparoscopically with minimal blood loss. The average number of lymph nodes
      sampled was 27.7 (range 14 to 35). RESULTS: Five patients required laparotomy,
      two to control bleeding, two to remove unsuspected intraabdominal disease, and
      one because of equipment failure. Four patients were rehospitalized within 30
      days of surgery, two with small bowel obstructions resulting from herniation of
      the intestine through 12 mm trocar sites and two others with deep vein
      thromboses. CONCLUSION: These preliminary results demonstrate an ability to
      complete surgical staging in patients with gynecologic malignancies by means of
      specific endoscopic techniques. However, there remains a need for continued
      evaluation of these techniques and the associated morbidities.

PMID- 7631667
TI  - Macrophage colony-stimulating factor 1, a clinically useful tumor marker in
      endometrial adenocarcinoma: comparison with CA 125 and the aminoterminal
      propeptide of type III procollagen.
AB  - OBJECTIVE: We investigated the clinical utility of macrophage colony-stimulating
      factor 1 versus CA 125 and the aminoterminal propeptide of type III procollagen
      in endometrial carcinoma. STUDY DESIGN: Serum levels of the three substances were
      measured in 159 patients with untreated endometrial adenocarcinoma and in 24
      patients treated with cytotoxic chemotherapy for recurrent endometrial
      adenocarcinoma. RESULTS: Initial concentrations of colony-stimulating factor 1,
      CA 125, and the aminoterminal peptide of type III procollagen were above the
      normal range in 73%, 11%, and 27%, respectively, of the patients. Colony
      stimulating factor 1 levels correlated with those of the aminoterminal peptide of
      type III procollagen (r = 0.3, p = 0.002) and CA 125 (r = 0.20, p = 0.036) in the
      total group and with those of the aminoterminal peptide of type III procollagen
      in stage I and II patients (r = 0.3, p = 0.0023). Colony-stimulating factor 1
      levels correlated significantly with tumor grade, whereas those of CA 125 and the
      aminoterminal peptide of type III procollagen correlated more closely with
      clinical stage. Mean colony-stimulating factor 1 levels (9.6 vs 7.7 ng/ml, p =
      0.04) and the frequency of elevated CA 125 levels (31% vs 8%, p = 0.048) were
      higher in patients with poor prognosis than in those with good prognosis. Colony
      stimulating factor 1, the aminoterminal peptide of type III procollagen, and CA
      125 levels were useful in monitoring clinical behavior of the disease in 88%,
      79%, and 63% of the cases, respectively. Levels of all three markers rose with
      disease progression, whereas colony-stimulating factor 1 and the aminoterminal
      peptide of type III procollagen fell with clinical responses to therapy.
      CONCLUSION: Elevated serum colony-stimulating factor 1 levels were the most
      accurate indicator of the presence and activity (progression, stabilization, or
      regression) of primary or recurrent disease. Accuracy was not further enhanced by
      measurement of CA 125 or the aminoterminal peptide of type III procollagen
      levels.

PMID- 7631668
TI  - Laser vaporization of the ovarian surface in polycystic ovary disease results in
      reduced ovarian hyperstimulation and improved pregnancy rates.
AB  - OBJECTIVE: Our purpose was to examine the efficacy of laser vaporization of the
      ovarian surface in polycystic ovary disease to reduce repeated ovarian
      hyperstimulation syndrome and thereby improve pregnancy outcome. STUDY DESIGN:
      Twenty-six infertile patients with polycystic ovary disease who previously had
      ovarian hyperstimulation syndrome after stimulation with human menopausal
      gonadotropin and who failed to conceive were studied. All patients were treated
      by potassium titanyl phosphate and neodymium-yttrium-aluminum-garnet laser and
      evaluated. Patients not ovulating spontaneously after vaporization were treated
      with either clomiphene citrate or human menopausal gonadotropin. RESULTS: After
      vaporization spontaneous ovulation was confirmed in six patients. For ovulation
      induction three patients received clomiphene citrate and 17 received human
      menopausal gonadotropin. Of the patients treated with human menopausal
      gonadotropin, mild ovarian hyperstimulation syndrome was found in three patients,
      and the incidence of ovarian hyperstimulation syndrome decreased significantly.
      Pregnancy was confirmed in 19 of 26 patients. CONCLUSION: Laser vaporization is
      promising for the prevention of ovarian hyperstimulation syndrome and improving
      pregnancy outcome in patients with polycystic ovary disease who have previously
      had ovarian hyperstimulation syndrome.

PMID- 7631669
TI  - Intrapelvic injection of menstrual endometrium causes endometriosis in baboons
      (Papio cynocephalus and Papio anubis).
AB  - OBJECTIVE: The Sampson hypothesis of retrograde menstruation as a cause of
      endometriosis was tested by determining the effect of intrapelvic injection of
      menstrual versus luteal endometrium on the incidence, peritoneal involvement, and
      stage of endometriosis. STUDY DESIGN: Seventeen baboons were injected
      retroperitoneally with luteal (n = 6) or menstrual (n = 7) endometrium and
      intraperitoneally with menstrual endometrium (n = 4). Laparoscopies were
      performed after 2 months in all animals and after 5 and 12 months in six and five
      primates injected with luteal and menstrual endometrium, respectively. RESULTS:
      The peritoneal endometriosis surface area, number of implants, and incidence of
      typical and red subtle lesions were significantly higher after retroperitoneal
      injection of menstrual than of luteal endometrium. By use of menstrual
      endometrium intraperitoneal seeding was more successful in causing endometriosis
      than was retroperitoneal injection. No significant changes in number or surface
      area of endometriotic lesions induced with retroperitoneal injection of luteal
      endometrium after 5 months were observed in the six baboons. At repeat
      laparoscopy 12 months after intrapelvic injection of menstrual endometrium
      progression was recorded in three of four regularly cycling animals, whereas
      regression was evident in one baboon that had become amenorrheic after induction.
      CONCLUSION: Intrapelvic injection of menstrual endometrium can cause peritoneal
      endometriosis and offers experimental evidence supporting the Sampson hypothesis.

PMID- 7631670
TI  - Estrogenic activity of RU 486 (mifepristone) in rat uterus and cultured uterine
      myocytes.
AB  - OBJECTIVE: Our purpose was to determine whether RU 486 (mifepristone) has direct
      estrogenic activity in uterine myocytes. STUDY DESIGN: Ovariectomized adult rats
      were treated with RU 486, and its effect on uterine oxytocin receptor
      concentration, as a marker of estrogenic activity, was measured. Results were
      compared with the induction by RU 486 of an estrogen-responsive reporter gene in
      a cultured Syrian hamster uterine myocyte cell line. RESULTS: Baseline oxytocin
      receptor concentration was 58.8 +/- 7.2 fmol/mg protein (mean +/- SEM) and
      increased to 227 +/- 49 fmol/mg with 17 beta-estradiol (2.5 micrograms/kg) and to
      145 +/- 18 fmol/mg after RU 486 (5 mg/kg) treatment, an effect that was inhibited
      by the antiestrogen ICI 182,780 (1.5 mg/kg). In the cultured Syrian hamster
      uterine myocyte cell line cells RU 486 (10(-6) mol/L) caused a 2.17 +/- 0.17-fold
      increase in the expression of the reporter gene versus 113.0 +/- 7.4-fold with 17
      beta-estradiol (10(-8) mol/L). The estrogenic activity of RU 486 was dependent on
      the presence of both estrogen receptor and the promoter's estrogen response
      element. CONCLUSION: RU 486 has a weak estrogen-like activity in uterine
      myocytes. This activity may partly explain the therapeutic effects of RU 486 on
      this target organ.

PMID- 7631671
TI  - Fetal fibronectin improves the accuracy of diagnosis of preterm labor.
AB  - OBJECTIVE: Our purpose was to assess the utility of cervicovaginal expression of
      fetal fibronectin in the diagnosis of preterm labor. STUDY DESIGN: Women seen
      between 24 and 34 weeks' gestation with symptoms of preterm labor, intact
      membranes, and cervical dilatation < 3 cm were enrolled at five university
      medical centers. Cervicovaginal swabs were obtained and assayed for the presence
      of fetal fibronectin by means of a monoclonal antibody assay. Results were
      compared with cervical dilatation and uterine contraction frequency as indicators
      of interval to delivery and delivery before 37 weeks. RESULTS: A total of 192
      eligible women at a mean gestational age of 30.8 +/- 2.9 weeks were enrolled from
      a population of 418 subjects screened. The rate of preterm birth was 32.3%
      (62/192). The mean interval from presentation to delivery was 25.3 +/- 24.1 days
      in the 45 subjects with a positive fibronectin assay and 52.4 +/- 24.8 days in
      the 147 subjects with a negative assay (p = 0.0001). The sensitivity,
      specificity, and positive and negative predictive values of fetal fibronectin
      expression for delivery < 37 weeks were 44% (27/62), 86% (112/130), 60% (27/45),
      and 76% (112/147). The fetal fibronectin assay was especially useful in
      predicting risk of delivery within 7 days (sensitivity 93% [13/14], specificity
      82% [146/178], positive predictive value 29% [13/45], and negative predictive
      value 99% [146/147]) and was notably superior to both cervical dilatation > 1 cm
      and contraction frequency greater than or equal to eight per hour (sensitivities
      29% and 42%, specificities 82% and 67%, positive predictive values 11% and 9%,
      and negative predictive values 94% and 94%, respectively. CONCLUSION:
      Cervicovaginal fetal fibronectin predicts delivery within 7 days more accurately
      than do cervical dilatation and contraction frequency in a population of women
      evaluated for early preterm labor.

PMID- 7631672
TI  - Impact of increasing carbohydrate intolerance on maternal-fetal outcomes in 3637
      women without gestational diabetes. The Toronto Tri-Hospital Gestational Diabetes
      Project.
AB  - OBJECTIVE: Our purpose was to assess maternal-fetal outcomes in patients with
      increasing carbohydrate intolerance not meeting the current criteria for the
      diagnosis of gestational diabetes. STUDY DESIGN: We conducted a prospective
      analytic cohort study in which nondiabetic women aged > or = 24 years, receiving
      prenatal care in three Toronto teaching hospitals, were eligible for enrollment.
      A glucose challenge test and an oral glucose tolerance test were administered at
      26 and 28 weeks' gestation, respectively; risk factors for unfavorable maternal
      fetal outcomes were recorded. Caregivers and patients were blinded to glucose
      values except when test results met the current criteria for gestational
      diabetes. RESULTS: Of 4274 patients screened, 3836 (90%) continued to the
      diagnostic oral glucose tolerance test. The study cohort was formed by the 3637
      (95%) patients without gestational diabetes, carrying singleton fetuses.
      Increasing carbohydrate intolerance in women without overt gestational diabetes
      was associated with a significantly increased incidence of cesarean sections,
      preeclampsia, macrosomia, and need for phototherapy, as well as an increased
      length of maternal and neonatal hospital stay. Multivariate analysis showed that
      increasing carbohydrate intolerance is an independent predictor for various
      unfavorable outcomes. CONCLUSION: Increasing maternal carbohydrate intolerance in
      pregnant women without gestational diabetes is associated with a graded increase
      in adverse maternal-fetal outcomes.

PMID- 7631674
TI  - Femur/foot length ratio for detection of Down syndrome: results of a multicenter
      prospective study. The Association Francaise pour le Depistage et la Prevention
      des Handicaps de l'Enfant Study Group.
AB  - OBJECTIVE: The aim was to determine the sensitivity and specificity of a short
      femur for detection of trisomy 21 in the second trimester. STUDY DESIGN: Thirty
      six investigators in 12 centers measured biparietal diameter and femur and foot
      lengths in 3582 14- to 24-week-old fetuses in mothers undergoing amniocentesis
      for age, history of genetic disorder, or laboratory signs. RESULTS: Among the
      various ratios for evaluating femur shortening the femur/foot ratio appeared to
      be the most discriminatory. At an upper cutoff level of 0.88 a sensitivity of 35%
      was obtained for 4.6% false positives in normal infants. However, to only obtain
      2.3% false positives, the cutoff limit had to be set at 0.85, giving a
      sensitivity of no more than 15%. CONCLUSION: Determination of the femur/foot
      ratio improves ultrasonographic detection of trisomy 21 in the second trimester,
      although for systematic use it would lead to an unacceptable number of
      unnecessary amniocenteses.

PMID- 7631673
TI  - Prevention of premature birth by screening and treatment for common genital tract
      infections: results of a prospective controlled evaluation.
AB  - OBJECTIVE: Our purpose was to analyze (1) the effects of prevalent lower
      reproductive tract infections and (2) the effect of systematic diagnosis and
      treatment to reduce risks of early pregnancy loss (< 22 weeks), preterm premature
      rupture of membrances, and overall preterm birth. STUDY DESIGN: A prospective,
      controlled treatment trial was conducted on 1260 women. During the first 7 months
      of the program (observation, phase I), women were examined at initiation of
      prenatal care for a panel of lower genital tract microorganisms and bacterial
      vaginosis. Women were followed up with reexaminations at 22 to 29 weeks and after
      32 weeks' gestation. The recommended treatments of the Centers for Disease
      Control (i.e., 300 mg of clindamycin orally twice daily for 7 days for bacterial
      vaginosis) were used for infected women during the second 8 months of the study
      (treatment, phase II). Data were analyzed according to intent to treat by means
      of univariate and multivariate methods. RESULTS: Overall, presence of bacterial
      vaginosis (32.5%) at enrollment was associated with pregnancy loss at < 22 weeks'
      gestation (relative risk 3.1, 95% confidence interval 1.4 to 6.9). Among women in
      the observation phase bacterial vaginosis was associated with increased risk of
      both preterm birth (relative risk 1.9, 95% confidence interval 1.2 to 3.0) and
      preterm premature rupture of membranes (relative risk 3.5, 95% confidence
      interval 1.4 to 8.9). Within this population (phase I) 21.9% of preterm birth
      overall (43.8% premature rupture of membranes) is estimated as attributable to
      bacterial vaginosis. Among women with bacterial vaginosis phase II (treatment)
      was associated with reduced preterm birth (relative risk 0.5, 95% confidence
      interval 0.3 to 0.9); there was a similar reduction for women with preterm
      premature rupture of membranes (relative risk 0.5, 95% confidence interval 0.2 to
      1.4). Women with both bacterial vaginosis and trichomoniasis were at highest risk
      of preterm birth (28%); treatment of both conditions (phase II) reduced preterm
      birth (17%) but did not eliminate this risk. Earlier patient enrollment and oral
      antibiotic treatment were associated with reduced preterm birth. CONCLUSIONS:
      This prospective, controlled trial confirms that the presence of bacterial
      vaginosis is associated with increased risks of pregnancy loss at < 22 weeks,
      preterm premature rupture of membranes, and preterm birth. Orally administered
      clindamycin treatment is associated with a 50% reduction of bacterial vaginosis
      linked preterm birth and preterm premature rupture of membranes. Women at risk
      for preterm birth or preterm premature rupture of membranes because of bacterial
      vaginosis or common genital tract infections should be screened, treated,
      reevaluated for cure, and re-treated if necessary.

PMID- 7631675
TI  - The impact of amniotic fluid volume assessed intrapartum on perinatal outcome.
AB  - OBJECTIVE: Our purpose was to determine the value of routine intrapartum amniotic
      fluid volume assessment on perinatal outcome. STUDY DESIGN: Patients admitted for
      labor and delivery who were ultimately delivered between January 1988 and June
      1989 with a gestational age > or = 26 weeks and who had an intrapartum amniotic
      fluid index composed the study group. The amniotic fluid index was determined by
      the four-quadrant technique on admission to labor and delivery. Oligohydramnios
      was defined as an amniotic fluid index < or = 5 cm (n = 170), borderline
      oligohydramnios as an amniotic fluid index 5.1 to 8.0 cm (n = 261), and normal
      amniotic fluid volume as an amniotic fluid index 8.1 to 20 cm (n = 336). Nine
      patients with an amniotic fluid index > 20 cm were excluded from data analysis.
      The oligohydramnios and borderline oligohydramnios groups were compared with the
      normal group with regard to antenatal, intrapartum, and postpartum variables.
      RESULTS: The groups had similar maternal age, parity, gestational age at
      delivery, and antenatal complications. Meconium-stained amniotic fluid occurred
      significantly less often in the oligohydramnios group compared with the normal
      group (relative risk 0.67, 95% confidence interval 0.49 to 0.92). However,
      variable decelerations occurred significantly more often in the oligohydramnios
      group compared with the normal group (relative risk 1.44, 95% confidence interval
      1.12 to 1.87), and cesarean delivery for fetal distress also occurred
      significantly more often (relative risk 6.83, 95% confidence interval 1.55 to
      30.4). There was no difference in Apgar scores or neonatal complications between
      groups. The efficacy of intrapartum-determined oligohydramnios predicting
      cesarean delivery for fetal distress gave a sensitivity of 78%, a specificity of
      74%, a positive predictive value of 33%, and a negative predictive value of 95%.
      CONCLUSION: The amniotic fluid index for detecting intrapartum oligohydramnios is
      a valuable screening test for subsequent fetal distress requiring cesarean
      delivery.

PMID- 7631676
TI  - The effect of oral magnesium substitution on pregnancy-induced leg cramps.
AB  - OBJECTIVE: Our purpose was to determine whether women with pregnancy-related leg
      cramps would benefit from oral magnesium supplementation. STUDY DESIGN: Seventy
      three women with pregnancy-related leg cramps were interviewed about their
      symptoms in a prospective, double-blind, randomized trial. Initial serum
      magnesium levels and diurnal magnesium excretion was determined in 50% of the
      patients. Oral magnesium or placebo was given for 3 weeks, after which new
      interviews and laboratory analyses were performed. RESULTS: Serum magnesium
      levels in these patients were at or below the lower reference limit, as is also
      often the case in healthy pregnant patients. Oral magnesium substitution
      decreased leg cramp distress (p < 0.05 compared with the placebo group, p < 0.001
      compared with initial complaints), but did not significantly increase serum
      magnesium levels, excess magnesium being excreted as measured by an increase in
      urinary magnesium levels (p < 0.002). CONCLUSION: Oral magnesium supplementation
      seems to be a valuable therapeutic tool in the treatment of pregnancy-related leg
      cramps.

PMID- 7631677
TI  - Maternal serum placental alkaline phosphatase level and risk for preterm
      delivery.
AB  - OBJECTIVE: The purpose of this study was to determine whether elevated
      midtrimester serum placental alkaline phosphatase levels are predictive of
      preterm delivery. STUDY DESIGN: By use of banked serum specimens from a sample of
      women who had received maternal serum alpha-fetoprotein screening, placental
      alkaline phosphatase values for multiples of the median were obtained from 270
      mothers who had experienced a preterm delivery and from 1598 mothers of term,
      appropriate-for-gestational-age infants. Specimens were analyzed for placental
      alkaline phosphatase by means of a monoclonal antibody enzyme-linked
      immunosorbent assay. Logistic regression was used to determine whether placental
      alkaline phosphatase was associated with preterm birth, while potential
      confounders were controlled for. RESULTS: Women with placental alkaline
      phosphatase levels > or = 2.0 multiples of the median were significantly more
      likely to be delivered of a preterm infant in the current pregnancy compared with
      women with levels < 2.0 multiples of the median (odds ratio 2.9, 95% confidence
      interval 2.1 to 3.9). The likelihood of preterm birth increased significantly
      with higher multiples of the median (p < 0.001). CONCLUSION: Women with elevated
      placental alkaline phosphatase levels are at increased risk for preterm delivery.
      Additional studies are needed to evaluate the clinical utility of placental
      alkaline phosphatase testing as a means of identifying mothers at risk for
      preterm birth.

PMID- 7631678
TI  - Acute pancreatitis in pregnancy.
AB  - OBJECTIVE: Our purpose was to determine the cause and describe the natural
      history of acute pancreatitis complicating pregnancy and its effect on maternal
      and perinatal outcomes. STUDY DESIGN: Over the last decade we admitted 43
      pregnant women with acute pancreatitis to our hospital. We reviewed presentation,
      diagnosis, management, and maternal and perinatal outcomes. RESULTS: The
      incidence of acute pancreatitis was one in 3333 pregnancies. The mean age of
      these 43 women was 24 years, 31 (72%) were multiparous, and pancreatitis was
      associated with biliary disease in 29 (68%). All had a favorable response to
      supportive therapy that included bowel rest, intravenous hydration, and
      antimicrobial therapy. Cholecystectomy was performed for persistent or recurrent
      biliary or pancreatic disease ante partum in eight women and post partum in
      another 12. Of 39 women who were delivered at our hospital, 32 were at term and
      their infants did well. The other six infants were delivered preterm; two were
      stillborn and another died after birth. One woman underwent a therapeutic
      abortion. CONCLUSIONS: Most pregnant women with acute pancreatitis have
      associated biliary tract disease. With prompt hospitalization, supportive care,
      and surgical intervention when indicated, maternal and fetal morbidity and
      mortality are not prohibitive. Fetal death and preterm delivery may result from
      severe disease.

PMID- 7631679
TI  - Urinary trypsin inhibitor prevents uterine muscle contraction by inhibition of
      Ca++ influx.
AB  - OBJECTIVE: The aim of this research was to elucidate the mechanism of action of
      urinary trypsin inhibitor, a Kunitz-type protease inhibitor, in suppressing
      uterine muscle contraction. STUDY DESIGN: An isometric uterine contraction test
      was used to study this inhibitory effect of urinary trypsin inhibitor on the
      myometrium. Oxytocin, prostaglandin F2 alpha, and lipopolysaccharide were used to
      stimulate myometrial contraction. Prostaglandins F2 alpha and E2 were measured in
      the buffer solution. Influx of calcium into uterine smooth muscle cells was
      assessed by digital imaging microscopy. RESULTS: After incubation with urinary
      trypsin inhibitor or fetal urine, myometrial contractions stimulated by oxytocin,
      prostaglandin F2 alpha or lipopolysaccharide were suppressed completely. The
      concentrations of prostaglandins F2 alpha and E2 in the buffer solution during
      the isometric contraction test were significantly increased by lipopolysaccharide
      stimulation, but when urinary trypsin inhibitor was present in the buffer
      solution the concentrations of prostaglandins F2 alpha or E2 did not change
      significantly. Preincubation with urinary trypsin inhibitor also inhibited
      calcium influx, resulting in no detectable change in the intracellular free
      calcium concentration of smooth muscle cells. CONCLUSION: We proposed that
      urinary trypsin inhibitor from fetal urine inhibits uterine muscle contraction by
      regulation of intracellular Ca++.

PMID- 7631680
TI  - Prostaglandin F2 alpha output by amnion-chorion-decidua: relationship with labor
      and prostaglandin E2 concentration at the amniotic surface.
AB  - OBJECTIVE: Our purpose was to evaluate prostaglandin F2 alpha output at fetal
      membrane surfaces relative to labor and to assess amniotic prostaglandin E2
      concentration changes on prostaglandin F2 alpha output. STUDY DESIGN: Intact and
      separated fetal membranes from 10 elective cesarean sections and nine vaginal
      deliveries were incubated in double-sided perfusion chambers. Prostaglandin F2
      alpha and 13,14-dihydro-15-keto-prostaglandin F2 alpha output was measured by
      radioimmunoassay. Alterations of prostaglandin F2 alpha and 13,14-dihydro-15-keto
      prostaglandin F2 alpha output were assessed after exogenous prostaglandin E2
      addition at amniotic surfaces of intact membranes. RESULTS: Prostaglandin F2
      alpha concentration was higher at maternal surfaces of intact but not separated
      membranes after labor (p = 0.0001). Amniotic 13,14-dihydro-15-keto-prostaglandin
      F2 alpha was increased in association with preceding labor (p = 0.038). Addition
      of prostaglandin E2 at the amniotic surface did not alter prostaglandin F2 alpha
      or 13,14-dihydro-15-keto-prostaglandin F2 alpha production. CONCLUSION:
      Prostaglandin F2 alpha concentration at the maternal surface of fetal membranes
      likely plays a critical role in induction or maintenance of myometrial
      contractions associated with term labor independent of amniotic fluid
      prostaglandin E2 concentrations.

PMID- 7631681
TI  - The interaction between regular exercise and selected aspects of women's health.
AB  - The public health initiative to increase women's participation in regular
      recreational exercise to the 90% level raises multiple theoretic concerns about
      its impact on the reproductive health of women. However, at all points in a
      woman's life the overall effect of regular exercise to appetite appears to be
      beneficial rather than harmful, and in the absence of other stressors, exercise
      performance must significantly exceed usual recreational levels to have an
      adverse effect on any aspect of a woman's reproductive life. Therefore even in
      elite athletes abnormalities of any part of the reproductive process (puberty,
      menstrual cyclicity, pregnancy, lactation, and menopause) should not be
      attributed solely to exercise without complete evaluation. While generally
      beneficial, the interaction between exercise and skeletal integrity is influenced
      by hormonal status and multiple exercise variables. Thus, whereas regular
      exercise at all ages appears to provide both short- and long-term benefit, the
      characteristics of the exercise regimen need to vary at different time points.

PMID- 7631682
TI  - Fetal cardiac function and ductus arteriosus during indomethacin and sulindac
      therapy for threatened preterm labor: a randomized study.
AB  - OBJECTIVE: The purpose of this randomized study was to evaluate the effects of
      indomethacin (10 patients) and sulindac (10 patients) given for 4-days on the
      fetal cardiac function and ductus arteriosus in pregnancies complicated by
      threatened premature labor between 28 and 32 gestational weeks. STUDY DESIGN: By
      use of pulsed color Doppler techniques the pulsatility index in fetal ductus
      arteriosus was calculated. Peak systolic velocities in the fetal ascending aorta
      and pulmonary trunk were also measured. By M-mode echocardiography both
      ventricular inner end-diastolic and end-systolic diameters were measured and
      ventricular fractional shortenings were calculated. Tricuspid valve regurgitation
      was evaluated by pulsed and color Doppler techniques. The ultrasonic examinations
      were made before and 4, 24, 48, and 72 hours after the start and 24 hours after
      the end of medication. RESULTS: Indomethacin significantly decreased the mean
      pulsatility index in fetal ductus arteriosus 4 hours after the beginning of
      medication. This decrease became greater later during medication, and it was
      associated with a significant increase in both ventricular inner end-diastolic
      diameters and with a significant decrease in right ventricular fractional
      shortening. The mean pulsatility index in the fetal ductus arteriosus increased
      to control values at 24 hours after the end of medication. Sulindac significantly
      decreased the mean pulsatility index in fetal ductus arteriosus only 24 hours
      after the beginning of medication. All other mean pulsatility index values did
      not differ from control values. Other cardiac parameters remained unchanged
      during sulindac treatment. CONCLUSION: Indomethacin has a significant reversible
      constrictive effect on the fetal ductus arteriosus that is associated with
      secondary changes, especially in the right ventricle. Sulindac seems to have only
      a mild and transient constrictive effect on the fetal ductus arteriosus.

PMID- 7631683
TI  - Long-term follow-up of mothers and their infants in a randomized trial on iron
      prophylaxis during pregnancy.
AB  - OBJECTIVE: A randomized trial comparing women who were given iron only if needed
      and those given iron prophylactically showed that routine prophylaxis is not
      crucial for mothers' or infants' health up to postpartum examination. This study
      investigated these infants' and mothers' subsequent health, as available in
      routine registers in a 7-year follow-up. STUDY DESIGN: Original data (N = 2693)
      were linked to the national population, birth, and hospital inpatient registers.
      RESULTS: The outcomes in the two groups were very similar: there were no
      statistically significant differences in deaths after birth, number or timing of
      infants' or mothers' hospitalizations, reasons for mothers' first
      hospitalization, number or timing of subsequent miscarriages or births, or
      problems or outcomes in the next birth. However, infants of the prophylactically
      supplemented group were more frequently hospitalized because of convulsions.
      CONCLUSION: This study does not support routine iron prophylaxis for well
      nourished pregnant women.

PMID- 7631685
TI  - The value of routine urine dipstick screening for protein at each prenatal visit.
AB  - OBJECTIVE: Our purpose was to determine whether dipstick urinalysis for protein,
      when performed as a routine screening test at each prenatal visit, predicts
      subsequent gestational outcome. STUDY DESIGN: All 3217 low-risk obstetric
      patients had dipstick urinalysis for protein at each prenatal visit. When there
      were any objective findings of a possible hypertensive disorder, the urine
      protein test for that visit was considered an indicated diagnostic test.
      Otherwise it was considered a routine screening test. Subjects were grouped
      according to whether those urine tests considered routine screening tests were
      positive for protein. The groups were then compared with regard to relevant
      pregnancy outcomes. RESULTS: There were no significant differences in the
      measured pregnancy outcomes between the groups. CONCLUSIONS: In low-risk women
      with no objective signs of a possible hypertensive disorder, routine dipstick
      proteinuria screening at each prenatal visit did not provide any clinically
      important information regarding pregnancy outcome.

PMID- 7631684
TI  - Resistance to activated protein C as a basis for venous thromboembolism
      associated with pregnancy and oral contraceptives.
AB  - OBJECTIVE: Inherited resistance to activate protein C, which is caused by a
      single factor V gene mutation, is a frequent risk factor for thrombosis. The
      purpose of this study was to determine the prevalence of activated protein C
      resistance in women with thromboembolic complications that had occurred in
      connection with pregnancy or use of oral contraceptives. STUDY DESIGN: Activated
      protein C resistance was analyzed in women with previous thromboembolic
      complications in connection with pregnancy (n = 34) or oral contraceptives (n =
      28), in healthy fertile women (n = 57), and in women during normal pregnancy (n =
      18). Results of the activated protein C resistance test were expressed as
      activated protein C ratios, values < 2 indicating activated protein C resistance.
      RESULTS: Activated protein C resistance was found in almost 60% of women with
      thromboembolic complications during pregnancy and in around 30% of women with
      thromboembolic complications during treatment with oral contraceptives. In
      nonpregnant controls approximately 10% had activated protein C resistance. In
      normal pregnancy activated protein C ratios were similar to those of normal
      controls. CONCLUSIONS: Activated protein C resistance, which is caused by a
      genetic defect in the factor V gene, was found to be highly prevalent in women
      with a history of thromboembolic complications during pregnancy. The gene defect
      is common in the general population, and the results evoke the question whether
      it would be reasonable to perform general screening for activated protein C
      resistance early during pregnancy or before prescription of oral contraceptives.

PMID- 7631686
TI  - Ambulatory blood pressure in pregnancy: comparison of the Spacelabs 90207 and
      Accutracker II monitors with intraarterial recordings.
AB  - OBJECTIVE: Our purpose was to compare systolic and diastolic blood pressures
      obtained with the Spacelabs 90207 (Spacelabs Medical Products, Dee Why,
      Australia) or Accutracker II (Suntech Medical Instruments, Melbourne, Australia)
      ambulatory blood pressure monitoring devices with intraarterial blood pressures
      in pregnant women. STUDY DESIGN: Direct (intraarterial) and resting blood
      pressures with the ambulatory blood pressure monitoring device were compared in
      39 pregnant women (14 Accutracker II and 25 Spacelabs 90207). RESULTS: The
      Accutracker II device underestimated direct systolic pressure by -9 (-13, -3) mm
      Hg (median, interquartile range) (p = 0.028) but gave similar diastolic pressure.
      The Spacelabs 90207 device gave similar systolic pressures but overestimated
      direct diastolic pressure by 7 (2, 12) mm Hg (p < 0.001). Variability for
      systolic and diastolic blood pressures within subjects was similar with the two
      devices. Both received poor gradings by standards of the British Hypertension
      Society and did not meet criteria of the Association for the Advancement of
      Medical Instrumentation, with intraarterial recordings used as the reference.
      CONCLUSIONS: The Accutracker II device significantly underestimated resting
      direct systolic pressure, whereas the Spacelabs 90207 device significantly
      overestimated resting direct diastolic pressure in pregnant women. Although poor
      gradings were achieved for both devices when intraarterial pressures were used as
      the reference, this is similar to comparisons of routine mercury sphygmomanometry
      with intraarterial recordings and does not mean these devices are unsuitable for
      use in pregnancy.

PMID- 7631687
TI  - Clinical experience with the oxytocin challenge test. 1972.

PMID- 7631689
TI  - Ultrasonographic and magnetic resonance imaging findings of a large asymptomatic
      retroperitoneal pelvic leiomyoma.
AB  - A large, asymptomatic retroperitoneal leiomyoma, originating at the level of the
      pelvic floor and occupying the entire pelvis, was noted during routine
      gynecologic examination. Ultrasonographic and magnetic resonance imaging findings
      of this unusual tumor are discussed.

PMID- 7631688
TI  - Massive congenital intracranial teratoma with skull rupture at delivery.
AB  - The majority of case reports concerning intracerebral tumors are almost equally
      divided between teratomas and gliomas. We report a case of congenital
      intracranial teratoma with suggested management. An 18-year-old woman at 30
      weeks' gestation in active labor because of severe fetal hydrocephalus and
      polyhydramnios was delivered by cesarean section. Spontaneous rupture of the
      neonatal skull led to delivery of a stillborn infant; a congenital teratoma was
      found. Although intracranial teratoma is a well-recognized entity in the
      differential diagnosis of pediatric brain tumors, massive congenital teratoma
      replacing cerebral hemispheres of a fetus has been seldom reported. Antenatal
      diagnosis of the neoplasm and abdominal delivery may not improve outcome.

PMID- 7631690
TI  - Post-cesarean section splenic rupture.
AB  - We report a case of splenic rupture after cesarean delivery for abruptio
      placentae. The diagnosis was not suspected until a laparotomy was performed.
      Diagnosis and management were complicated by disseminated intravascular
      coagulation and renal failure. The importance of early diagnosis and management
      modalities are discussed.

PMID- 7631691
TI  - Fetal methemoglobinemia: a cause of nonimmune hydrops fetalis.
AB  - A case of nonimmune hydrops fetalis resulting from fetal methemoglobinemia is
      presented. A woman with a pregnancy at 17 weeks' gestation was admitted after
      combustion gas intoxication. Although the mother totally recovered, the fetus
      showed signs of nonimmune hydrops fetalis at follow-up. Fetal methemoglobin
      levels were very high.

PMID- 7631692
TI  - Massive fetomaternal hemorrhage treated with serial combined intravascular and
      intraperitoneal fetal transfusions.
AB  - One of the many causes of fetal hydrops is fetomaternal hemorrhage. This report
      presents a pregnancy with fetomaternal hemorrhage that was treated with serial
      combined intravascular and intraperitoneal fetal transfusions, resulting in a
      good outcome. A 26-year-old woman seen for ultrasonographic evaluation was found
      to have a fetus with hydrops fetalis. Fetal blood sampling demonstrated severe
      fetal anemia (hematocrit 16.4%). The initial Kleihauer-Betke test result on
      maternal blood was 6% fetal cells. The fetus was transfused five times over a 24
      day period by means of a combined intravascular and intraperitoneal route. The
      fetus also received one platelet transfusion for thrombocytopenia. The pregnancy
      resulted in a good fetal outcome without the need for postpartum transfusion.
      This case represents successful treatment of fetal anemia and nonimmune hydrops
      with a serial combined intravascular and intraperitoneal transfusion technique.

PMID- 7631693
TI  - A new diagnostic method to detect ectopic pregnancy at a very early stage.

PMID- 7631694
TI  - Nocturnal hyperventilation in pregnancy--reversal with nasal continuous positive
      airway pressure.
AB  - A 41-year-old mother with a twin pregnancy had disabling hyperventilation with
      severe nocturnal symptoms at 25 weeks' gestation. The nocturnal attacks were
      relieved with nasal continuous positive airway pressure, which she successfully
      used throughout the rest of the pregnancy. Nasal continuous positive airway
      pressure could be an option to control severe pregnancy-induced hyperventilation.

PMID- 7631695
TI  - The genetic implication for preceding generations of the prenatal diagnosis of
      interrupted aortic arch in association with unsuspected DiGeorge anomaly.
AB  - We present a case of prenatally diagnosed interrupted aortic arch with a
      ventricular septal defect in the presence of maternal congenital heart disease,
      which led to the detection of segmental monosomy of chromosome 22q11.2 in both
      patients. The implications of detecting a microdeletion and the importance of a
      multidisciplinary approach to prenatal diagnosis and counseling are discussed.

PMID- 7631696
TI  - Necrotizing fasciitis in the puerperium.
AB  - A case of necrotizing fasciitis in a healthy woman taking a nonsteroidal
      antiinflammatory drug in the puerperium is presented. The role of increased
      virulence of group A streptococci and the association of necrotizing fasciitis
      with nonsteroidal antiinflammatory drugs is reviewed.

PMID- 7631697
TI  - Uterine rupture in association with alkaloidal ("crack") cocaine abuse.
AB  - The use of alkaloidal ("crack") cocaine in pregnancy can result in systemic and
      focal vasoconstriction and abnormal uterine contractions forceful enough to cause
      the complete rupture of a gravid uterus along a previous vertical cesarean
      section scar. A 43-year-old woman was admitted to the emergency department with
      acute abdominal pain at 34 weeks' gestation. She had had a low vertical cesarean
      section 3 years previously for breech presentation with acute fetal distress at
      28 weeks' gestation. The patient had a history of heavy "crack" abuse and
      admitted to inhaling "crack" throughout the day until 4 hours before admission.
      Within 15 minutes after presentation a laparotomy was performed, revealing an
      infant floating in the abdominal cavity. A live baby was promptly delivered, and
      the ruptured uterus was repaired. The patient was discharged 4 days post partum.
      "Crack" cocaine, through its known effects on the vasculature and contractility
      of the myometrium, likely facilitated the uterine rupture in this patient. The
      edges of the rupture wound were surprisingly clean, with little bleeding, perhaps
      owing to the drug's vasoconstrictive effects. It was therefore feasible to repair
      the uterus as an alternative approach to hysterectomy.

PMID- 7631698
TI  - Chorioamnionitis caused by Capnocytophaga: case report.
AB  - Intraamniotic infection is a significant cause of perinatal morbidity.
      Capnocytophaga, a gram-negative anaerobe found in the oral cavity, has been
      implicated as an unusual cause of neonatal sepsis. We report a patient in whom
      this unusual organism was identified and describe the postpartum and neonatal
      courses.

PMID- 7631699
TI  - Interleukin-10 messenger ribonucleic acid in human placenta: implications of a
      role for interleukin-10 in fetal allograft protection.
AB  - OBJECTIVE: Our purpose was to determine whether interleukin-10 is expressed in
      human placental tissue, which might imply a role for it in fetal allograft
      protection. STUDY DESIGN: Detection of interleukin-10 messenger ribonucleic acid
      in human placental tissue and in human placental JAR cells by reverse
      transcription-coupled polymerase chain reaction was studied. RESULTS: Interleukin
      10 messenger ribonucleic acid was detected in human placental tissue from term
      mothers and in human placental JAR cells. Sequence analysis of the expected
      interleukin-10 complementary deoxyribonucleic acid fragment revealed 100%
      homology to authentic interleukin-10 complementary deoxyribonucleic acid.
      CONCLUSION: Our results indicated that human placental tissue from term mothers
      expressed high levels of interleukin-10 messenger ribonucleic acid, suggesting
      that cells that produce interleukin-10 and that are associated with the placenta
      may play a role in preventing rejection of the fetal allograft by the mother.

PMID- 7631700
TI  - Scientific basis and therapeutic regimens for use of antenatal glucocorticoids.

PMID- 7631701
TI  - Evidence from multicenter networks on the current use and effectiveness of
      antenatal corticosteroids in low birth weight infants.

PMID- 7631702
TI  - Antenatal corticosteroid administration and neonatal outcome in very low birth
      weight infants: the NICHD Neonatal Research Network.

PMID- 7631703
TI  - Antenatal corticosteroid treatment and neonatal outcomes for infants 501 to 1500
      gm in the Vermont-Oxford Trials Network.

PMID- 7631704
TI  - Observational evidence for the efficacy of antenatal steroids from randomized
      studies of surfactant replacement.

PMID- 7631705
TI  - Antenatal steroids and neonatal outcomes in controlled clinical trials of
      surfactant replacement. The American Exosurf Neonatal Study Group I and The
      Canadian Exosurf Neonatal Study Group.

PMID- 7631706
TI  - Associations between use of antenatal corticosteroids and neonatal outcomes
      within the Exosurf Neonatal Treatment Investigational New Drug Program.

PMID- 7631707
TI  - Practice variation in the use of corticosteroids: a comparison of eight data
      sets.

PMID- 7631708
TI  - Maternal corticosteroid and tocolytic treatment and morbidity and mortality in
      very low birth weight infants.

PMID- 7631709
TI  - Increased fetal plasma prostaglandin E2 concentrations during fetal placental
      embolization in pregnant sheep.
AB  - OBJECTIVE: The purpose of this study was to examine the effect of chronic fetal
      placental embolization on fetal plasma prostaglandin E2 concentrations. STUDY
      DESIGN: Fourteen pregnant sheep were studied (seven embolized and seven controls)
      for 10 days between 0.84 and 0.91 of gestation. Daily injections of
      nonradioactive microspheres were made to decrease fetal arterial oxygen content
      by 30% to 35% of preembolization values. RESULTS: In response to repeated
      embolization, fetal plasma prostaglandin E2 concentrations increased
      significantly on day 1, declined to near control levels on days 2 to 6, but were
      significantly elevated again after day 7. Maternal prostaglandin E2 levels
      remained unchanged throughout the study. Fetal plasma prostaglandin E2 levels
      increased significantly with decreasing fetal oxygenation when fetal arterial
      oxygen content was < 2.0 mmol/L. CONCLUSION: We conclude that there is increased
      production of prostaglandin E2 by the placenta during progressive fetal hypoxemia
      induced by fetal placental embolization. We speculate that the progressive
      increase in prostaglandin E2 may be an important hormonal adaptive mechanism to
      maintain fetal homeostasis during the development of placental insufficiency.

PMID- 7631710
TI  - Relationship between antenatal steroid administration and grades III and IV
      intracranial hemorrhage in low birth weight infants. The NICHD Neonatal Research
      Network.

PMID- 7631711
TI  - An exploration of opinion and practice patterns affecting low use of antenatal
      corticosteroids.

PMID- 7631712
TI  - Cost savings from the use of antenatal steroids to prevent respiratory distress
      syndrome and related conditions in premature infants.

PMID- 7631713
TI  - Antenatal corticosteroid therapy: a meta-analysis of the randomized trials, 1972
      to 1994.

PMID- 7631714
TI  - Meta-analysis of randomized controlled trials of antenatal corticosteroid for the
      prevention of respiratory distress syndrome: discussion.

PMID- 7631715
TI  - Vascular clamping model not new.

PMID- 7631716
TI  - Emergency cervical cerclage after the first delivery in a twin pregnancy with
      dichorionic placenta.

PMID- 7631717
TI  - Mechanism underlying phasic contractions of pregnant rat myometrium simulated by
      aluminum fluoride.

PMID- 7631718
TI  - Beat-to-beat variation.

PMID- 7631719
TI  - Japanese endometriosis progression: universally applicable?

PMID- 7631720
TI  - Managing premature ruptured membranes at term.

PMID- 7631721
TI  - Induction of labor versus expectant management: does it matter?

PMID- 7631722
TI  - The control of blood loss at cesarean section with intramyometrial prostaglandin
      F2 alpha analog versus intravenous synthetic oxytocin.

PMID- 7631723
TI  - Laminaria versus Dilapan osmotic cervical dilators for second-trimester abortion.

PMID- 7631724
TI  - The effect of low amniotic pressure without oligohydramnios on fetal lung
      development in a rabbit model.
AB  - OBJECTIVE: Our purpose was to examine fetal lung development in reduced
      intraamniotic pressure without amniotic fluid loss. STUDY DESIGN: A circular
      portion of uterine wall measuring 1 cm in diameter was excised while the
      chorionic and amniotic membranes were left intact at the twenty-third day of
      gestation in New Zealand White rabbits. The chorionic and amniotic membranes
      herniated spontaneously through the defect. RESULTS: Amniotic pressure was
      significantly reduced after herniation. Lung weight/body weight ratios at term
      were significantly reduced in experimental fetuses compared with controls.
      Residual amniotic fluid volumes at term did not differ. Histopathologic
      examination of lung specimens showed that fetal lungs had not matured in the
      experimental group as fully as in the control group. CONCLUSION: This
      experimental study demonstrated that low amniotic pressure impaired fetal lung
      development, even without oligohydramnios.

PMID- 7631725
TI  - Red blood cell vitamin E concentrations in fetuses are related to but lower than
      those in mothers during gestation. A possible association with maternal
      lipoprotein (a) plasma levels.
AB  - OBJECTIVE: The purpose was to establish which blood characteristic of vitamin E
      status were highly correlated between mothers and fetuses during gestation. STUDY
      DESIGN: Twenty-four pregnant women were selected because of suspicion of
      toxoplasmosis or other disease and malformation or intrauterine growth delay
      justifying cord blood puncture. After maternal and fetal blood was collected,
      analyses of plasma and red blood cell vitamin E contents were performed together
      with analyses of standard lipid parameters and lipoprotein (a) in maternal plasma
      and fatty acid compositions of maternal and fetal red blood cells. RESULTS: The
      maternal population was characterized by a plasma lipid-normalized vitamin E mean
      content higher (3.5 mmol/mol lipids) than usually found in nonpregnant adults.
      There was no relationship between plasma and red blood cell vitamin E contents.
      This was also true for fetuses. When the vitamin E status of mothers was compared
      with that of fetuses, we found no correlation in plasma vitamin E in the whole
      population and in the high lipoprotein (a) (> 300 mg/L) and low lipoprotein (a)
      (< 300 mg/L) groups. In contrast, statistically significant correlations appeared
      between maternal and fetal red blood cell contents and red blood cell relative
      charges in vitamin E in the whole population, whereas still higher correlations
      occurred in the high lipoprotein (a) group (r = 0.94 for the red blood cell
      content). Improved correlations were also found in the high lipoprotein (a) group
      for the interrelationship between vitamin E and plasma lipid contents
      (cholesterol and triglycerides), whereas improvement was noted in the low
      lipoprotein (a) group by positive correlation between age and vitamin E red blood
      cell content or red blood cell relative charge. CONCLUSION: Determination of red
      blood cell vitamin E and plasma lipoprotein (a) in mothers could be useful in
      antenatal blood analysis in cases of risk of prematurity at birth, to prevent
      peroxidative membrane damage in neonates, and > 85% of the mothers in the current
      population would benefit from vitamin E supplementation from the viewpoint of the
      fetal red blood cell vitamin E requirement in spite of the rather high maternal
      lipid-normalized vitamin E plasma content.

PMID- 7631726
TI  - An animal model for hemolytic disease of the fetus and newborn. I.
      Alloimmunization techniques.
AB  - OBJECTIVE: Our purpose was to establish an animal model for hemolytic disease of
      the fetus and newborn by developing red blood cell alloimmunization techniques in
      the rabbit. STUDY DESIGN: Twenty-six nonpregnant New Zealand White or Red does
      underwent blood typing to identify them as homozygous at the HgA or HgF red blood
      cell antigen locus. Alloimmunization to incompatible red blood cells was
      attempted through a series of subcutaneous injections using complete then
      incomplete Freund's adjuvant. RESULTS: Successful induction of an antibody
      response occurred in 96% of cases. The median response in FF rabbits was 2560
      (range 40 to 10,240), whereas the response in AA does was 2560 (range 320 to
      20,480). These responses were not statistically different (p = 0.77). Responses
      were categorized as poor, moderate, or good. No difference was noted between FF
      and AA does in distribution of the categories of response (p = 0.53). CONCLUSION:
      Red blood cell alloantibodies of high titer can be induced successfully in the
      rabbit.

PMID- 7631727
TI  - Immediate maternal and neonatal effects of low-forceps delivery according to the
      new criteria of The American College of Obstetricians and Gynecologists compared
      with spontaneous vaginal delivery in term pregnancies.
AB  - OBJECTIVE: Our purpose was to investigate the maternal and neonatal effects of
      elective low-forceps delivery, as currently defined by the 1988 criteria of The
      American College of Obstetricians and Gynecologists. STUDY DESIGN: During a 6
      month period we conducted a prospective study that included 50 nulliparous term
      parturients who were randomly allocated to spontaneous or elective low-forceps
      delivery. Patients with either maternal or fetal disorders that could affect the
      outcome were excluded. All deliveries were attended by three experienced
      obstetricians. RESULTS: Spontaneous and forceps delivery group were similar
      regarding maternal or gestational age, fetal scalp pH, antepartum maternal
      hemoglobin and hematocrit levels, maternal outcome, mean birth weight, and number
      of neonates with low Apgar scores or cord arterial pH < 7.20. In the spontaneous
      delivery group the time elapsed since randomization to delivery was significantly
      longer (18 vs 10.2 minutes, p < 0.001) and the mean cord arterial pH was
      significantly lower (7.23 vs 7.27, p = 0.01) than in the forceps delivery group.
      CONCLUSION: Elective low forceps delivery may be used to shorten the second stage
      of labor without immediate maternal or neonatal side effects.

PMID- 7631728
TI  - Sequential urinalysis improves evaluation of fetal renal function in obstructive
      uropathy.
AB  - OBJECTIVES: The purpose of our study was to determine whether sequential
      vesicocenteses improve the evaluation of renal damage, compared with single urine
      sampling in obstructive uropathy. STUDY DESIGN: A total of 29 fetuses with
      complete obstructive uropathy underwent a minimum of three sequential complete
      vesicocenteses at 48- to 72-hour intervals. First and last urine values were
      analyzed for multiple parameters. The ability of first versus last urine values
      to detect the presence of renal damage was compared according to postnatal or
      fetal autopsy information. RESULTS: Fetuses with minimal renal damage had
      patterns of decreasing hypertonicity and last urine values below cutoff
      thresholds indicative of favorable prognosis. Fetuses with significant renal
      damage had higher initial values and patterns of increasing hypertonicity. For
      five of six parameters, last urine samples were more predictive of renal damage
      than first urine samples. CONCLUSION: Last urine values together with pattern-of
      change trend analysis after serial vesicocenteses improve diagnostic precision in
      fetuses with complete obstructive uropathy.

PMID- 7631729
TI  - Three surgical procedures for genuine stress incontinence: five-year follow-up of
      a prospective randomized study.
AB  - OBJECTIVE: Our purpose was to evaluate and compare the long-term results of the
      Kelly plication, modified Pereyra needle suspension, and Burch urethropexy for
      the treatment of stress urinary incontinence in women. STUDY DESIGN: One hundred
      twenty-seven consecutive women underwent surgery at the gynecologic urology
      division at Women's Hospital, Los Angeles County-University of Southern
      California Medical Center between January 1986 and June 1987. The only indication
      for surgery was stress urinary incontinence. Women with previously failed
      antiincontinence procedures were excluded. Fifty-three patients were
      premenopausal and 74 postmenopausal. History, physical examination,
      urethocystoscopy, cotton swab test, filling cystometry, urethral pressure profile
      at rest and on cough, and uroflowmetry were performed preoperatively, 3 months, 1
      year, and 5 years postoperatively. The subjects and surgeons were randomly
      allocated to one of three surgical procedures: group 1 had anterior colporrhaphy
      with Kelly plication, group 2 had modified Pereyra needle urethropexy, and group
      3 had Burch urethropexy. One hundred seven women were available after 1 year, and
      93 were the subjects of the 5-year evaluation. Fisher exact text, chi 2, t test,
      and paired t test were used for statistical analysis. RESULTS: The results of the
      1-year postoperative evaluation has been previously published. The objective
      success rate for groups 1, 2, and 3 after 5 years was 37%, 43%, and 82%,
      respectively, and the difference was statistically significant. The drop in the
      success rate in 4 years was 26%, 22%, and 7% for groups 1, 2, and 3,
      respectively. Urodynamically all three procedures significantly increased the
      abdominal pressure transmission to the urethra, when successful. Ninety-one
      percent of women after the Burch procedure had a negative cotton swab test after
      5 years compared with 46% for the Pereyra and 30% for the Kelly procedures.
      CONCLUSIONS: In our hands the Burch urethropexy has a higher cure rate that holds
      over time when compared with the modified Pereyra needle suspension and the Kelly
      plication. The lower incidence of the positive cotton swab test in women after
      Burch urethropexy may be proof of a better anatomic suspension of the bladder
      neck.

PMID- 7631730
TI  - Pelvic floor electrical stimulation in the treatment of genuine stress
      incontinence: a multicenter, placebo-controlled trial.
AB  - OBJECTIVE: Our purpose was to determine the efficacy of transvaginal electrical
      stimulation in treating genuine stress incontinence. STUDY DESIGN: This was a
      multicenter, prospective, randomized, double-blind, placebo-controlled 15-week
      trial comparing the use of an active pelvic floor stimulator with a sham device.
      Thirty-five women used an active unit and 17 control subjects used sham devices.
      Weekly and daily voiding diaries were recorded throughout the trial. Urodynamic
      testing, including pad test and subtracted cystometry, was done before and at the
      end of device use. Pelvic muscle strength was measured at baseline and at the end
      of the trial. Patients scored their symptoms on visual analog scales and
      completed quality-of-life questionnaires before and after therapy. RESULTS:
      Significant improvements from baseline were found in patients using active
      devices but not in controls. Comparisons of changes from baseline between active
      device and control patients showed that active-device patients had significantly
      greater improvement in weekly (p = 0.009) and daily (p = 0.04) leakage episodes,
      pad testing (p = 0.005), and vaginal muscle strength (p = 0.02) when compared
      with control subjects. Significantly greater improvement was also found for both
      visual analog scores of urinary incontinence (p = 0.007) and stress incontinence
      (p = 0.02), as well as for subjective reporting of frequency of urine loss (p =
      0.002), and urine loss with sneezing, coughing, or laughing (p = 0.02), when
      compared with controls. Pad testing showed that stress incontinence was improved
      by at least 50% in 62% of patients using an active device compared with only 19%
      of patients using sham devices (p = 0.01). Voiding diaries showed at least 50%
      improvement in 48% of active-device patients compared with 13% of women using the
      sham device (p = 0.02). No irreversible adverse effects were noted in either
      group. CONCLUSIONS: Transvaginal pelvic floor electrical stimulation was found to
      be a safe and effective therapy for genuine stress incontinence.

PMID- 7631731
TI  - Evaluation of preoperative cardiac risk index values in patients undergoing
      vaginal surgery.
AB  - OBJECTIVE: Our purpose was to evaluate the Goldman and the New York Heart
      Association cardiac risk index values in a female surgical population and to
      evaluate age, hypertension, ischemic heart disease, glucose intolerance, cardiac
      arrhythmia, and estrogen replacement therapy as risk factors for perioperative
      cardiac morbidity in older women undergoing major vaginal surgery. STUDY DESIGN:
      A retrospective analysis was performed of perioperative cardiac morbidity in
      consecutive patients undergoing elective vaginal surgery between August 1987 and
      October 1993. RESULTS: Four hundred six patients were entered in the study. Eight
      patients had perioperative cardiac morbidity. The Goldman cardiac risk index and
      the New York Heart Association functional classification of heart disease were
      not significant indicators of perioperative cardiac morbidity in this group of
      patients. In the postmenopausal subgroup of 168 patients hypertension (p = 0.033)
      and ischemic heart disease (p = 0.004) were statistically significant risk
      factors for perioperative cardiac morbidity. Glucose intolerance, cardiac
      arrhythmia, and estrogen replacement therapy were not significant predictors.
      CONCLUSION: The Goldman cardiac risk index and the New York Heart Association
      functional classification of heart disease are of questionable utility in a
      female surgical population undergoing elective vaginal surgical procedures.
      Hypertension and ischemic heart disease are risk factors for perioperative
      cardiac morbidity in a postmenopausal subgroup of these patients.

PMID- 7631732
TI  - A prospective two-year study of progestin given alone in postmenopausal women:
      effect on lipid and metabolic parameters.
AB  - OBJECTIVE: A controlled study was conducted to assess the long-term effect of a
      progestin with very low androgenic potency given alone on serum lipoprotein
      profile, serum renin substrate, sex hormone-binding globulin levels, and serum
      antithrombin III activity in early postmenopausal women. STUDY DESIGN: Thirty
      five early postmenopausal women who had not received any form of hormonal
      treatment after menopause were randomly assigned to a 2-year regimen of 500
      micrograms of a progestin derived from 19-norprogesterone (promegestone) or a
      placebo for 21 days of a 28-day treatment cycle. Serum lipid and lipoprotein
      levels and other biochemical parameters were measured in the two groups, and
      differences were sought by statistical analysis. RESULTS: After 2 years of
      treatment the women in the two groups showed no statistically significant
      variation from baseline values in the concentrations of any of the biochemical
      parameters studied. CONCLUSIONS: The results show that a progestin with very low
      androgenic activity given alone has no influence on lipid profile and hepatic
      synthesis of several proteins in early postmenopausal women.

PMID- 7631733
TI  - Immunohistochemical studies of human uteroplacental tissues from first-trimester
      spontaneous abortion.
AB  - OBJECTIVE: Atypical expression of human leukocyte antigen histocompatibility
      molecules or complement regulatory proteins by placental trophoblast has been
      hypothesized as a mechanism for spontaneous abortion. The purpose of this study
      was to determine expression of these proteins by placental villous trophoblast
      and to identify leukocyte populations within uteroplacental tissues from women
      with their first spontaneous abortion, their fourth or more recurrent spontaneous
      abortion, and from women having elective pregnancy termination. STUDY DESIGN:
      Fresh uteroplacental tissues were obtained at 6 to 9 weeks' gestation from eight
      women with their first spontaneous abortion, 20 women experiencing their fourth
      or more unexplained recurrent spontaneous abortion, and 20 women having an
      elective pregnancy termination. These tissues were analyzed immunohistochemically
      for human leukocyte antigen histocompatibility molecules (class I and II major
      histocompatibility complexes), complement regulatory proteins (CD46, CD55), and
      leukocyte phenotypes (CD45, CD3, CD14, CD56). RESULTS: There was absence of cell
      surface expression of class I and II human leukocyte antigen molecules but strong
      trophoblast expression of complement regulatory proteins in all villous placental
      samples. Leukocyte infiltration was noted in all decidual specimens. The
      predominant decidual leukocyte population was CD3-negative, CD56-positive cells,
      except in four cases of recurrent abortion where the normal ratio (< or = 2:3) of
      CD14-positive macrophages to CD56-positive leukocytes was > 2:1. There was an
      unusual retention of maternal class II major histocompatibility complex-positive
      leukocytes within intervillous spaces attached to the apical surface of
      syncytiotrophoblast from one individual with recurrent abortion. CONCLUSION: Our
      data do not support the hypothesis that some cases of recurrent spontaneous
      abortion result from atypical expression of human leukocyte antigen
      histocompatibility molecules or lack of complement regulatory protein expression
      by placental villous trophoblast. These data suggest that occasional cases of
      recurrent spontaneous abortion could be associated with an impaired CD56-positive
      leukocyte response in the early decidualized endometrium.

PMID- 7631734
TI  - Steroid hormone effects on the proliferation of human ovarian surface epithelium
      in vitro.
AB  - OBJECTIVE: The histologically bland-appearing epithelium of the human ovary is
      responsible for approximately 90% of ovarian cancers. Capitalizing on our ability
      to propagate this tissue in vitro, we have begun to characterize the steroid
      hormone responsiveness of the human ovarian surface epithelium. STUDY DESIGN:
      Primary cultures of the human ovarian surface epithelium are characterized as
      normal epithelium on the basis of morphologic features, normal karyotype, and
      immunohistochemistry demonstrating AE1/AE3 cytokeratin positivity and factor VIII
      negativity. Estrogen and progestin receptors were quantitatively analyzed with a
      standard receptor-ligand binding assay. Cellular proliferation in response to 1 x
      10(-7) mol/L 17 beta-estradiol, progesterone, dihydrotestosterone, and
      dexamethasone were assessed by means of cell counts and a tetrazolium-based
      colorimetric assay. RESULTS: Scatchard analyses identified 8.8 x 10(3) estrogen
      receptors per cell in the premenopausal human ovarian surface epithelium cells,
      whereas the postmenopausal cells were negative for estrogen receptors. A total of
      3.2 to 13.0 x 10(3) progestin receptors per cell was identified, with variable
      progestin receptor expression in the postmenopausal cells. No significant effect
      on cell growth could be demonstrated as a result of any of the steroid hormones
      investigated under the study conditions. CONCLUSIONS: Expression of estrogen and
      progestin receptors in human ovarian surface epithelium cells may be related to
      menopausal status. Steroid hormones, however, did not influence cell
      proliferation under these experimental conditions.

PMID- 7631735
TI  - Extracellular matrix hyaluronan is a determinant of the endothelial barrier.
AB  - We measured the hydraulic conductivity (Lp) of the extracellular matrix (ECM)
      obtained after detaching bovine pulmonary microvascular endothelial (BPMVEC) and
      bovine pulmonary arterial endothelial cell (BPAEC) monolayers from the ECM at
      different days postseeding. From day 1 to day 5 in culture, the total Lp (i.e.,
      of cell monolayer + ECM) decreased from basal values of 17.1 +/- 4.0 to 8.5 +/-
      1.6 x 10(-6) cm.s-1.cmH2O-1 in BPAEC (P < 0.05) and 7.6 +/- 1.1 to 3.7 +/- 0.8 in
      BPMVEC (P < 0.05), respectively, and on day 5 the total Lp values were lower in
      BPMVEC than in BPAEC (P < 0.05). On the 5th day, ECM Lp was 55.0 +/- 8.3 in BPAEC
      and 10.7 +/- 0.9 cm.s-1.cmH2O-1 in BPMVEC (P < 0.05), indicating that the
      contribution of ECM to the total Lp was greater in BPMVEC than in BPAEC.
      Treatment of [3H]acetate-labeled ECM with Streptomyces hyaluronidase (HAse; 6
      U/ml for 10 min) released sixfold greater radioactivity in BPMVEC compared with
      untreated BPMVEC controls; a similar treatment of BPAEC did not release
      detectable radioactivity indicative of a higher hyaluronan content in the BPMVEC
      ECM. HAse treatment reduced the differences in total Lp between BPMVEC and BPAEC
      at different days postseeding. Moreover, on the 5th day after seeding, the ECM Lp
      of BPMVEC increased to a greater extent after HAse treatment than the ECM of
      BPAEC. These data indicate that the hyaluronan component of the ECM is an
      important determinant of the endothelial liquid-exchange barrier.

PMID- 7631736
TI  - Increases in [Ca2+]i mediated by the 92.5-kDa putative cell membrane receptor for
      HCMV gp86.
AB  - We determined that changes in intracellular Ca2+ concentration ([Ca2+]i) occur in
      human fibroblasts within the first hour of human cytomegalovirus (HCMV) infection
      when viral adsorption and fusion take place, and we investigated whether such
      changes also occur in response to monoclonal anti-idiotype antibodies (MAb2) that
      mimic HCMV gp86 and bind to a 92.5-kDa putative cell membrane receptor for gp86.
      Digitized image analysis of fura 2-loaded human embryonic lung fibroblasts
      indicated specific transient increases in [Ca2+]i beginning in some cells within
      the first 5 min of incubation with cross-linked MAb2 (70-750 nM, P < 0.01), which
      were similar in timing and intracellular distribution to those induced by HCMV. A
      primary source of Ca2+ appeared to be intracellular Ca2+ stores, since prior
      depletion of these stores with 30 nM thapsigargin inhibited the response (91.7 +/
      8.6%, P < 0.01); influx of Ca2+ from the extracellular medium was apparently
      necessary to maintain the intracellular Ca2+ stores. Transient increases in
      inositol trisphosphate (IP3) occurred in response to MAb2 (up to 3,329 +/- 84%, P
      < 0.001) or HCMV (92.8 +/- 19%, P < 0.01) during this same time period. These
      data suggest that the 92.5-kDa receptor for HCMV gp86 mediates an increase in IP3
      and subsequent release of Ca2+ from intracellular stores.

PMID- 7631737
TI  - Arg-Gly-Asp peptide increases endothelial hydraulic conductivity: comparison with
      thrombin response.
AB  - The contribution of integrin receptors to the regulation of endothelial
      permeability was studied using cultured bovine pulmonary microvascular
      endothelial cell (BPMVEC) monolayers by the measurement of hydraulic conductivity
      (Lp). Treatment of monolayers with a peptide containing the sequence Gly-Arg-Gly
      Asp-Ser-Pro (GRGDSP) (0.85 mM) to compete for the RGD sequence of extracellular
      matrix (ECM) proteins increased endothelial Lp threefold, whereas the control
      peptide Gly-Arg-Gly-Glu-Ser-Pro had no effect on Lp. This action of GRGDSP on Lp
      was not significantly altered by dibutyryl adenosine 3',5'-cyclic monophosphate
      (DBcAMP; 0.5 mM). Endothelial Lp increased twofold when the monolayers were
      challenged with alpha-thrombin (5 x 10(-8) M for 10 min), and this response was
      completely reversed by DBcAMP. The strength of adhesion of endothelial cells was
      estimated by evaluating the ability of endothelial cells to remain attached to
      ECM after treating the monolayers with 0.05% trypsin plus 0.5 mM EDTA. Exposure
      of the monolayers to either GRGDSP or alpha-thrombin significantly reduced the
      strength of adhesion to the ECM. DBcAMP prevented the antiadhesive effect of
      alpha-thrombin but not that of GRGDSP. Treatment of the monolayers with either
      alpha-thrombin or GRGDSP caused formation of intercellular gaps, but only the
      thrombin-induced intercellular gaps were accompanied by reorganization of actin
      filaments. These results indicate that integrin binding to ECM proteins regulates
      an important determinant of endothelial permeability and that alpha-thrombin and
      GRGDSP increase endothelial cell monolayer permeability by different mechanisms.

PMID- 7631738
TI  - TMB-8 and dibucaine induce tyrosine phosphorylation and dephosphorylation of a
      common set of proteins in platelets.
AB  - Dibucaine and 8-(N,N-diethylamino)octyl 3,4,5-trimethoxybenzoate (TMB-8), which
      are local anesthetics, affect diverse functions of many cell types. For example,
      platelet aggregation is inhibited by both, and both cause changes in platelet
      morphology and structure. Little is known of the mechanisms. We found that both
      dibucaine (0.125-0.5 mM) and TMB-8 (0.25-1.0 mM) induced rapid tyrosine
      phosphorylation of several platelet proteins (160, 70-75, and 40 kDa) and
      dephosphorylation of a 62- to 64-kDa protein detectable by a specific
      antiphosphotyrosine monoclonal antibody (4G10). Platelet aggregation induced by
      alpha-thrombin (10 nM) was inhibited by the local anesthetics in approximately
      the same dose range. Neither dibucaine nor TMB-8 induced activation of protein
      kinase C (PKC) or myosin light-chain kinase. Their activation was not essential
      for tyrosine phosphorylation induced by local anesthetics. However, an increase
      in tyrosine phosphorylation of several proteins (95-130 kDa) induced by alpha
      thrombin (10 nM) was inhibited by dibucaine (0.5 mM) or TMB-8 (0.5 mM).
      Furthermore, when dibucaine (0.5 mM) was added 1 min after addition of alpha
      thrombin (10 nM), disaggregation was paralleled to dephosphorylation of many
      proteins, including those mentioned. Tyrosine phosphorylation and
      dephosphorylation of specific proteins may account for some of the diverse
      effects of local anesthetics on platelets and other cells. Addition of TMB-8 (0.5
      mM) or dibucaine (0.5 mM) also inhibited activation of PKC, induced by alpha
      thrombin (10nM), suggesting that some of the inhibitory effects of dibucaine or
      TMB-8 may be due to inhibitory effects of local anesthetics on PKC.

PMID- 7631739
TI  - Acid incubation increases NHE-3 mRNA abundance in OKP cells.
AB  - With the use of degenerate primers based on conserved amino acid sequences in
      human, rat, and rabbit Na/H exchanger-3 (NHE-3), a polymerase chain reaction
      product was obtained from reverse-transcribed OKP (a clonal opossum kidney cell
      line) mRNA and used to screen an OKP cDNA library. The clone obtained predicted
      an amino acid sequence that was 86% identical to rat NHE-3, 33% to NHE-1, 35% to
      NHE-2, and 30% to NHE-4. Expression of the corresponding cRNA in Xenopus oocytes
      induced 22Na uptake with ethylisopropylamiloride. (EIPA) resistance similar to
      that of the OKP Na/H antiporter. On RNA blot, the cDNA labeled a 9.5-kb
      transcript whose abundance was increased 2.2-fold by 24-h incubation of OKP cells
      at pH 7.0 and 2.5-fold by 24-h incubation at pH 6.8. The acid-induced increase in
      NHE-3 mRNA was detectable at 12 h and increased further at 24 h. Incubation in
      acid media caused an increase in EIPA-resistant Na/H antiporter activity that
      preceded the increase in NHE-3 mRNA. In summary, OKP cells express an NHE-3
      transcript that encodes an EIPA-resistant Na/H antiporter and is chronically
      regulated by acid.

PMID- 7631740
TI  - Protein kinase C isoforms in rat kidney proximal tubule: acute effect of
      angiotensin II.
AB  - The present study examined the effect of phorbol esters, Ca2+, and angiotensin II
      (ANG II) on protein kinase C (PKC) isoforms in the rat proximal tubule. The
      immunoblot analysis of PKC isoforms of particulate and cytosolic fractions of
      proximal tubules revealed immunoreactive proteins when antibodies against PKC
      alpha, -delta, -epsilon, and -zeta, but not -beta and -gamma were used. Phorbol
      dibutyrate (PDBU) induced the translocation of PKC-alpha, -delta, and -epsilon,
      whereas an inactive phorbol ester had no effect. PDBU and ionomycin increased
      particulate PKC specific activity from 0.67 +/- 0.09 to 1.56 +/- 0.18 and 0.96 +/
      0.04 pmol.microgram protein-1.2 min-1, respectively. ANG II (10(-7) M) induced a
      time-dependent increase in particulate PKC-alpha immunoreactivity observed after
      2 min and maintained for 12 min. Particulate PKC-epsilon immunoreactivity
      increased after 4 min. Meanwhile, PKC-delta and -zeta were not modified by ANG
      II. Accordingly, ANG II elicited a rise in the specific activity of the
      particulate PKC, which increased to 0.89 +/- 0.09 pmol.micrograms protein-1.2 min
      1 after 2 min. This was inhibited by a preincubation in the presence of 10(-5) M
      losartan, specific inhibitor of angiotensin subtype 1 receptors. These data
      indicate that PKC-alpha and -epsilon are potential candidates to regulate the
      activity of Na+/H+ and Na(+)-HCO3- transporters because they are translocated
      with a time course fitting with that of the reported effect of ANG II on those
      transporters.

PMID- 7631741
TI  - Ca(2+)-induced mitochondrial membrane permeabilization: role of coenzyme Q redox
      state.
AB  - Rotenone-poisoned rat liver mitochondria energized by succinate addition, after a
      5-min period of preincubation in presence of 10 microM Ca2+, produce H2O2 at much
      faster rates, undergo extensive swelling, and are not able to retain the membrane
      potential and accumulated Ca2+. Similar results were obtained when a suspension
      of rat liver mitochondria preincubated in anaerobic medium for 5 min was
      reoxygenated. The addition of either ethylene glycol-bis(beta-aminoethyl ether)
      N,N,N',N'-tetraacetic acid, ruthenium red, catalase, or dithiothreitol, just
      before succinate or O2 addition, prevented mitochondrial swelling, indicating the
      involvement of Ca2+, reactive oxygen species, and oxidation of membrane protein
      thiols in this process of membrane permeabilization. Inhibition of mitochondrial
      swelling by cyclosporin A suggests that the membrane alterations observed under
      these experimental conditions are related to opening of the permeability
      transition pore. The presence of carbonyl cyanide p
      trifluoromethoxyphenylhydrazone, which prevents Ca2+ cycling across the membrane,
      did not inhibit mitochondrial swelling when Ca2+ influx into the mitochondrial
      matrix was driven by a high Ca2+ gradient. When rotenone plus antimycin A
      poisoned mitochondria were energized by N,N,N',N'-tetramethyl-p-phenylenediamine,
      which reduces respiratory chain complex IV, mitochondrial swelling did not occur,
      unless succinate, which reduces coenzyme Q, was also added. It is concluded that
      reduced coenzyme Q is the electron source for oxygen radical production during
      Ca(2+)-stimulated oxidative damage of mitochondria.

PMID- 7631742
TI  - Regulation of whole cell currents by cytosolic cAMP, Ca2+, and Cl- in rat fetal
      distal lung epithelium.
AB  - The whole cell patch-clamp technique was used to study ionic conductances in
      fetal distal lung epithelial (FDLE) cells. In unstimulated FDLE cells, K+
      conductances were detected in lowered intracellular Cl- concentration ([Cl-]i, <
      or = 50 mM). The whole cell currents of FDLE cells were increased by elevation of
      intracellular Ca2+ concentration ([Ca2+]i) or intracellular adenosine 3',5'
      cyclic monophosphate (cAMP) concentration ([cAMP]i). The elevation of [Ca2+]i
      activated the K+ currents. The amiloride-blockable whole cell currents were
      activated by [cAMP]i of 1 mM with [Cl-]i of 20 mM and were more frequently
      detected in the pipette solution without ethylene glycol-bis(beta-aminoethyl
      ether)-N,N,N',N'-tetraacetic acid (EGTA) than with it (0.5 mM). When the [Cl-]i
      was fixed at 50 or 145 mM, however, the increase in these currents was not
      detected even with cAMP and without EGTA. The amiloride-blockable currents were
      detected in both the Na+ and K+ pipette solutions. Thus the increase in amiloride
      blockable whole cell currents was due to the activation of nonselective cation
      channels. In FDLE cells treated with terbutaline, which is a beta 2-adrenergic
      receptor agonist, or forskolin, these currents were detected in the pipette
      solution containing 20 mM Cl- but were suppressed with time when the pipette
      solution contained 50 or 145 mM Cl-. It seems likely that maintenance of [Cl-]i
      at the lowered level is an important requirement for the FDLE cells to activate
      the amiloride-blockable whole cell currents. It is proposed that cellular
      mechanisms, such as cell shrinkage, exist to reduce the [Cl-]i in response to
      cAMP.

PMID- 7631743
TI  - K+ self-exchange by the Na+ pump: regulation by P(i) and metabolic perturbations.
AB  - We have previously demonstrated that the Na(+)-K+ pump on the basolateral
      membrane of the rabbit cortical collecting duct can function in the K+/K+
      exchange mode. Increasing intracellular phosphate in red blood cells inhibits the
      Na+ pump and increases K+/K+ exchange. We found that maneuvers designed to
      increase intracellular phosphate in collecting duct cells caused an increase in
      K+/K+ exchange. Subjecting the cells to a metabolic insult (cyanide) increased
      K+/K+ exchange by the pump as judged by its ouabain sensitivity and lack of
      electrogenic or conductive characteristics. The results demonstrate that the rate
      of K+/K+ exchange by the Na(+)-K+ pump can be altered by changes in intracellular
      phosphate over a range that is physiologically or pathologically achievable. The
      results also suggest a mechanism for inhibition of vectorial Na+ transport during
      metabolic stress.

PMID- 7631744
TI  - An outwardly rectifying K+ current active near resting potential in human retinal
      pigment epithelial cells.
AB  - Currents in freshly dissociated adult human retinal pigment epithelial (RPE)
      cells were studied using the perforated patch-clamp technique. The zero-current
      potential (V0) averaged -48.9 +/- 7.7 mV (n = 50). Depolarizing voltage pulses
      from -70 mV evoked an outward current that activated with first-order kinetics
      and that did not inactivate during prolonged depolarizations. Repolarizing the
      membrane potential produced tail currents that reversed near the K+ equilibrium
      potential, indicating that the sustained outward current was carried mainly by
      K+. The outwardly rectifying K+ conductance (gK) had an activation threshold
      voltage near -60 mV and was half-maximal at -37 mV. Approximately 25% of gK was
      active at the average V0. The K+ current was nearly completely blocked by 2 mM
      Ba2+ but was relatively insensitive to 20 mM tetraethylammonium. The kinetics,
      voltage dependence, and blocker sensitivity of this current clearly distinguish
      it from delayed rectifier K+ currents previously identified in RPE cells. We
      conclude that the sustained outward K+ current may help establish the resting
      potential of the apical and/or basolateral membranes and may also participate in
      K+ transport across the RPE.

PMID- 7631745
TI  - The highly selective low-conductance epithelial Na channel of Xenopus laevis A6
      kidney cells.
AB  - In Na-reabsorbing tight epithelia, the rate-limiting step for Na transport is the
      highly selective low-conductance amiloride-sensitive epithelial Na channel (type
      1 ENaC). In rat distal colon, type 1 ENaC is made of three homologous subunits.
      The aim of this study was to identify the corresponding genes of the renal
      channel from the kidney-derived A6 cell line of Xenopus laevis. Three homologous
      subunits were identified and coexpressed in the Xenopus oocyte system. The
      reconstituted channel had all the characteristics of the native type 1 ENaC
      described in A6 cells: 1) high selectivity, 2) low single-channel conductance, 3)
      slow gating kinetics, and 4) high affinity for amiloride. Transcripts for alpha-,
      beta-, and gamma-subunits of the Xenopus epithelial Na channel (xENaC) were
      detected in A6 kidney cells, Xenopus kidney, lung, and to a lesser extent in
      stomach and skin. Each subunit of the xENaC shares approximately 60% overall
      identity with the corresponding rat homologue (alpha, beta, and gamma rENaC). Our
      data suggest that the triplication of the ENaC subunits occurred before the
      divergence between mammalian and amphibian lineages.

PMID- 7631746
TI  - Cloning, tissue distribution, and functional analysis of the human Na+/N+
      exchanger isoform, NHE3.
AB  - We previously isolated a 1.4-kb partial cDNA from a human kidney cortex library.
      Using both library screening and reverse transcription-polymerase chain reaction
      of human kidney RNA, we obtained the entire coding region of the human NHE3 cDNA.
      The human NHE3 cDNA encoded a protein of 834 amino acids with a calculated
      relative molecular weight of 92,906. It exhibited 89 and 88% amino acid identity
      with rat and rabbit NHE3, respectively. The stable transfection of a composite
      human NHE3 cDNA into Na+/H+ exchanger-deficient PS120 cells established Na+/H+
      exchange. Functionally, human NHE3 was similar to the rabbit and rat NHE3
      homologues, being relatively resistant to inhibition by amiloride, half-maximal
      inhibition (IC50) = 49.0 microM, and ethylisopropylamiloride, IC50 = 6.6 microM,
      and being stimulated by fibroblast growth factor but inhibited by phorbol 12
      myristate 13-acetate. However, unlike the rabbit or rat NHE3, human NHE3 message
      was not restricted to kidney, intestine, stomach, and brain. Northern analysis of
      multiple human tissues detected NHE3 message, in descending order, as follows:
      kidney >> small intestine >> testes > ovary > colon = prostate > thymus >
      peripheral leukocyte = brain > spleen > placenta. Message in the kidney, small
      intestine, and colon was primarily of 6.7 kb, whereas both 6.7- and 8.9-kb bands
      were expressed nearly equivalently in the other tissues. No NHE3 message was
      detected in the human heart, lung, liver, skeletal muscle, or pancreas.

PMID- 7631747
TI  - Developmental regulation of membrane protein sorting in Drosophila embryos.
AB  - We have examined the process of membrane protein targeting in the polarized cells
      of the developing Drosophila melanogaster embryo. Human placental alkaline
      phosphatase (PLAP) is a glycosylphosphatidyl inositol-linked protein that
      accumulates at the apical membranes of mammalian epithelial cells. A chimeric
      construct composed of the transmembrane and cytosolic portions of the vesicular
      stomatitis virus G protein coupled to the ectodomain of PLAP, termed PLAPG, has
      been found to behave as a basolateral protein (D. A. Brown, B. Crise, and J. K.
      Rose. Science Wash. DC 232: 34-47, 1989). The subcellular distributions of these
      proteins were examined in the epithelial and neuronal tissues of transgenic
      Drosophila embryos. In the surface ectoderm, both PLAP and PLAPG were restricted
      to the basolateral membranes throughout development. Internal epithelia derived
      from the surface ectoderm accumulated PLAP at their apical surfaces, whereas
      PLAPG retained its basolateral distribution. The redistribution of PLAP from the
      basolateral to the apical plasma membrane was found to be coincident with the
      invagination of the surface epithelium to form internal structures, suggesting
      that the sorting pathways that function in the epithelium of the Drosophila
      embryo are developmentally regulated.

PMID- 7631749
TI  - Utilization and preferred metabolic pathway of ketone bodies for lipid synthesis
      by isolated rat hepatoma cells.
AB  - Morris hepatoma 7777 cells freshly isolated from highly malignant tumors grown in
      the hindlimb of buffalo rats actively convert ketone bodies to cholesterol and
      fatty acids. On the basis of results obtained with (-)-hydroxycitrate, an
      inhibitor of the ATP citrate lyase enzyme, the metabolic pathway for acetoacetate
      conversion to lipids is exclusively cytoplasmic, whereas that for 3
      hydroxybutyrate involves both extra- and intramitochondrial compartments.
      Subcellular distribution studies indicated accumulation and compartmentation of 3
      hydroxybutyryl CoA primarily in the cytoplasm of hepatoma cells incubated with
      either ketone body. In contrast, the compartmentation of acetoacetyl CoA is
      dependent on whether the substrate is acetoacetate or 3-hydroxybutyrate. With
      acetoacetate, the acetoacetyl CoA is entirely cytoplasmic, whereas with 3
      hydroxybutyrate, it is equally divided between the intra- and extramitochondrial
      compartments. The results are discussed in terms of the known and proposed
      metabolic pathways for lipid synthesis from ketone bodies, particularly that from
      3-hydroxybutyrate.

PMID- 7631748
TI  - Action of insulin on Na(+)-K(+)-ATPase and the Na(+)-K(+)-2Cl- cotransporter in
      3T3-L1 adipocytes.
AB  - The Na(+)-K(+)-ATPase presents several different isoforms of its alpha- and beta
      subunits. We detected alpha 1- and beta 1-mRNA transcripts and polypeptides in
      3T3-L1 fibroblasts; during differentiation into adipocytes, alpha 1-mRNA
      decreased, alpha 2-mRNA was induced, beta 1-mRNA dropped to undetectable levels,
      and beta 2-mRNA was never expressed, suggesting that 3T3-L1 adipocytes may
      express an unidentified Na(+)-K(+)-ATPase beta-subunit isoform. Insulin rapidly
      increased ion pump activity [ouabain-sensitive 86Rb+(K+) uptake] in 3T3-L1
      fibroblasts and adipocytes without changing the plasma membrane concentration of
      alpha 1- or alpha 2-subunits as determined by subcellular membrane fractionation
      and immunoblotting or by [3H]ouabain binding to intact cells. Monensin, which
      raises the concentration of intracellular Na+, increased Na(+)-K+ pump activity,
      and no further stimulation was achieved with insulin. The stimulation of the pump
      by insulin was reduced by bumetanide, an inhibitor of the Na(+)-K(+)-2Cl-
      cotransporter, and was prevented by omission of extracellular Cl-. Insulin
      increased both ouabain-sensitive and bumetanide-sensitive 86Rb+(K+) uptake. These
      results suggest that insulin activation of the Na(+)-K(+)-ATPase in 3T3-L1
      adipocytes is mediated by an elevation in intracellular Na+ that is likely the
      consequence of Na(+)-K(+)-2Cl- cotransporter activation.

PMID- 7631751
TI  - Role of basolateral Na(+)-K(+)-Cl- cotransport in HCl secretion by amphibian
      gastric mucosa.
AB  - In amphibians and mammals, luminal H+ secretion by the stomach requires Cl-. It
      is widely accepted that a basolateral Cl-/HCO3- exchanger in the acid-secreting
      oxyntic cell restores the Cl- deficit resulting from apical HCl secretion. In
      this study, we used reverse transcriptase-polymerase chain reaction (RT-PCR) to
      generate a 1,200-bp fragment specific to a basolateral isoform of the Na(+)-K(+)
      Cl- cotransporter in the gastric fundus of Necturus maculosus. By Northern
      analysis, we observed that gastric mucosa expresses greater than fivefold higher
      levels of mRNA encoding this cotransporter than any other tissue in the
      gastrointestinal tract. Feeding results in > 100% increases in mRNA levels in
      acid-secreting fundic mucosa but does not alter mRNA levels in the neighboring
      and non-acid-secreting antral mucosa or duodenum. Flux measurements using in
      vitro fundic mucosae indicate that acid secretion requires Na+ in the nutrient
      (i.e., serosal side) perfusate, is modulated by changes in nutrient K+ levels,
      and is inhibited by nutrient solutions containing 50 microM bumetanide, a
      recognized blocker of Na(+)-K(+)-Cl- cotransport. These findings suggest that
      this basolateral transporter plays a dominant and previously unsuspected role in
      secretion of HCl across the apical membrane.

PMID- 7631752
TI  - Effect of Prozac on whole cell ionic currents in lens and corneal epithelia.
AB  - Prozac (fluoxetine), a compound used therapeutically in humans to combat
      depression, has substantial effects on ionic conductances in rabbit corneal
      epithelial cells and in cultured human lens epithelium. In corneal epithelium, it
      reduces the current due to the large-conductance potassium channels that dominate
      this preparation. Its effects seem largely to decrease the open probability while
      leaving the single-channel current amplitude unaltered. In cultured human
      epithelium, currents from calcium-activated potassium channels and inward
      rectifiers are unaffected by Prozac. Delayed-rectifier potassium currents are
      reduced by Prozac in a complicated way that involves both gating and single
      channel current amplitude. Fast tetrodotoxin-blockable sodium currents are also
      decreased by Prozac in this preparation. For all of these ion conductance
      effects, Prozac concentrations of 10(-5) to 10(-4) M are required. Whereas these
      levels are 10- to 100-fold higher than the plasma levels achieved in therapeutic
      use in humans, they are comparable to or less than levels needed for many other
      blockers of the ionic conductances studied here.

PMID- 7631750
TI  - Glutathione removal reveals kinases as common targets for K-Cl cotransport
      stimulation in sheep erythrocytes.
AB  - K-Cl cotransport is activated by swelling, lowering of cellular free Mg (Mgi),
      and thiol modification of erythrocytes. Direct actions by thiol reagents on the K
      Cl cotransport complex were separated from indirect effects through nonoxidative
      changes in cellular glutathione (GSH). We used 1-chloro-2,4-dinitrobenzene
      (CDNB), which, conjugated to GSH, is extruded from the erythrocyte as a
      thioether. CDNB caused a small biphasic effect (inhibition and stimulation) on K
      Cl cotransport and, at 1 mM, abolished its stimulation by N-ethylmaleimide (NEM),
      diazenedicarboxylic acid bis[N,N-dimethylamide], methyl methanethiosulfonate, and
      staurosporine, a kinase inhibitor, independent of the order of treatment. Hence,
      NEM and other activating-thiol reagents, and perhaps GSH removal itself, target
      unidentified kinases involved in activation of K-Cl cotransport. CDNB also
      abrogated K-Cl cotransport stimulation by Mgi depletion independent of the order
      of treatment, indicating inhibition at a second site nearer to the transporter.
      Furthermore, CDNB treatment elevated and rendered K-Cl cotransport insensitive to
      osmotic shrinkage, suggesting uncoupling from the regulator.

PMID- 7631753
TI  - Shrinkage-induced activation of Na+/H+ exchange in primary rat astrocytes: role
      of myosin light-chain kinase.
AB  - Primary rat astrocytes exposed to hyperosmotic solutions undergo Na(+)-dependent
      amiloride-sensitive alkalinization of 0.36 U [measured with the pH-sensitive
      fluorescent dye 2',7'-bis(carboxyethyl)-5(6)-carboxy-fluorescein], suggesting
      that shrinkage-induced alkalinization is due to activation of Na+/H+ exchange
      (NHE). Alkalinization is maintained for at least 20 min, and is readily
      reversible and ATP dependent. Hyperosmotic solutions produced no increase of
      intracellular Ca2+ or adenosine 3',5'-cyclic monophosphate (cAMP). Loading cells
      with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, a Ca2+ chelator,
      or depleting cells of protein kinase C (PKC) had no effect on activation of NHE.
      Thus shrinkage-induced activation of NHE does not involve cAMP, Ca2+, or PKC.
      However, ML-7, an inhibitor of myosin light-chain kinase (MLCK), inhibited
      shrinkage-induced activation with a half-maximal inhibition of 56 microM. This
      activation was also inhibited by 500 microM N-(6-aminohexyl)-5-chloro-1
      naphthalenesulfonamide, 100 microM chlorpromazine, and 50 microM trifluoperazine,
      all calmodulin inhibitors. Shrinkage increased the phosphorylation of an 18-kDa
      protein that colocalizes with myosin light chain. Our data suggest that shrinkage
      induced activation of NHE in astrocytes occurs via a novel pathway involving
      activation of calmodulin-dependent MLCK and phosphorylation of myosin light
      chain.

PMID- 7631754
TI  - Functional coupling of Na(+)-K(+)-2Cl- cotransport and Ca(2+)-dependent K+
      channels in vascular endothelial cells.
AB  - To determine whether the activation of Na(+)-K(+)-2Cl- cotransport by Ca(2+)
      mobilizing agonists is a direct effect of Ca2+ or is secondary to activation of
      Ca(2+)-dependent K+ channels [via cell shrinkage or decreased intracellular Cl-
      concentration ([Cl-]), we measured K+ fluxes in aortic endothelial cells in
      response to ATP and bradykinin. With either agonist there was an immediate
      bumetanide-insensitive efflux inhibitable by the K+ channel blockers
      tetrabutylammonium (TBA, 23 mM) and quinidine (1 mM), followed several minutes
      later by increased bumetanide-sensitive efflux or influx (Na(+)-K(+)-2Cl-
      cotransport). ATP induced a loss of cell K+ that was prevented by TBA and
      augmented by bumetanide. Both TBA and quinidine prevented the stimulation of
      cotransport by agonists but not by hypertonic shrinkage. Raising medium [K+] to
      prevent K+ loss also blocked activation of cotransport by agonists. The results
      indicate that the stimulation of Na(+)-K(+)-2Cl- cotransport by Ca2+ is not
      direct but instead is indirect via activation of Ca(2+)-dependent K+ channels and
      a resulting decrease in cell volume and intracellular [Cl-]. This suggests that
      at least one role of Na(+)-K(+)-2Cl- cotransport in endothelial cells is to
      maintain cell volume and intracellular [Cl-] during agonist stimulation.

PMID- 7631755
TI  - Imaging real-time neurite outgrowth and cytoskeletal reorganization with an
      atomic force microscope.
AB  - An atomic force microscope was used to image the morphology and structural
      reorganization of rat NIH/3T3 fibroblasts and PC-12 cells growing in petri
      dishes. NIH/3T3 fibroblasts had a uniform morphology and an extensive
      cytoskeletal network. Cell thickness varied from approximately 2-3 microns above
      the nucleus to approximately 20-30 nm over the distal processes, and cytoskeletal
      fibers as small as 30 nm wide were observed. Imaging over an extended period of
      time showed a limited degree of cytoskeletal reorganization. Localized force
      dissection did not induce significant retraction of cellular processes and
      immediate cell death. Differentiating PC-12 cells with a neuronal phenotype had a
      nonuniform morphology, abundant cytoskeletal elements, neuritic processes, and
      growth cones. The cell thickness varied from approximately 5-8 microns over the
      nucleus to approximately 100-500 nm over the neuritic processes; growth cones
      approximately 50-700 nm wide and end structures approximately 30-150 nm wide were
      visible. Repeated imaging showed reorganization of the growth cone, especially
      the appearance and disappearance of beadlike features and fibrous organization.
      Thus an atomic force microscope can be used for high-resolution real-time studies
      of the dynamic subcellular mechanisms that drive cell behavior.

PMID- 7631756
TI  - Calcium transients in intact rat skeletal muscle fibers in agarose gel.
AB  - Intact single fibers enzymatically dissociated from rat flexor digitorum brevis
      muscle were suspended in 0.5% low-melting-temperature agarose gel to minimize
      fiber movement during action potentials or trains of action potentials. Resting
      Ca2+ concentration ([Ca2+]) and changes in [Ca2+] were monitored using the
      fluorescent calcium indicator fura 2. The time course and waveform of [Ca2+]
      transients during an action potential or trains of action potentials in fibers in
      agarose were calculated using kinetic parameters previously determined to correct
      for the calcium-fura 2 kinetic delay. Half times of the calculated calcium
      transients for single action potentials were 30-fold briefer than the original
      fura 2 signals. To confirm the time course and waveform of the calculated calcium
      transients, changes in [Ca2+] were monitored using the more rapidly equilibrating
      calcium indicator mag-fura 2. [Ca2+] transients for fibers containing fura 2 had
      very similar time courses and waveforms as mag-fura 2 signals from other fibers,
      indicating that the corrections for the calcium-fura 2 kinetic delay were
      accurate. The advantages of the agarose gel suspension are discussed.

PMID- 7631757
TI  - Dynamic micromechanical properties of cultured rat atrial myocytes measured by
      atomic force microscopy.
AB  - The atomic force microscope (AFM) was used to quantify micromechanical properties
      (i.e., localized to an area of approximately 0.015 microns 2) of cultured rat
      atrial myocytes. Quiescent cells in calcium-free solution were quite compressible
      over the nuclear region, e.g., a force of 3-4 nN produced 180-225 nm cell
      indentation. Transverse stiffness of quiescent cells increased by approximately 2
      fold after an increase in extracellular calcium from 0 to 5 mM and by
      approximately 16-fold after fixation with Formalin. There was five- to eightfold
      variation in stiffness of quiescent cells over the cell surface, such that
      stiffness was lowest over the nuclear region, and it increased toward the cell
      periphery. These regional variations correlated with the cytoskeletal
      heterogeneity as revealed by the AFM and fluorescence imaging. Localized
      contractile activity of beating cells could be monitored in terms of the surface
      deformation with high transverse spatial (approximately 1-3 nm) and temporal (60
      100 microseconds) resolutions. Alterations in cell contractile activity with
      physiological perturbations and dynamic changes in cell stiffness during a single
      contraction could be observed. These results demonstrate the feasibility of AFM
      based characterization of highly localized cellular micromechanical properties.
      Relationships among localized cell mechanical behavior and the underlying
      biochemical and/or structural environment, a crucial aspect in understanding
      cellular (dys)function, can now be directly examined.

PMID- 7631758
TI  - Osmoregulation of GPC:choline phosphodiesterase in MDCK cells: different effects
      of urea and NaCl.
AB  - The organic osmolyte, glycerophosphocholine (GPC), accumulates in renal cells in
      response to high concentrations of either NaCl or urea, despite the very
      different effects of these solutes on cell function and volume. Together, high
      levels of these solutes increase GPC amount in Madin-Darby canine kidney cells by
      inhibiting its enzymatic degradation. The present study tests the effects of NaCl
      and urea, individually, on GPC accumulation and its degradation. A technique was
      developed to determine the absolute rate of GPC degradation by measuring the
      initial rate of disappearance of [3H]GPC (pulsed into the cells by hypotonic
      shock) and the specific activity of GPC in the cells. The mass of GPC in the
      cells was measured by another newly developed method, a sensitive
      chemiluminescent assay. We find that exposure to high NaCl or urea decreases the
      absolute rate of cellular GPC degradation by approximately one-half during the
      first 20.5 h. Reductions in GPC degradation are accompanied by commensurate
      decreases in the activity of GPC:choline phosphodiesterase (GPC:PDE; EC 3.1.4.2),
      an enzyme that catalyzes degradation of GPC. Activity of GPC:PDE falls > 50% in
      cells exposed for 2 h to high osmolality. Inhibition is sustained for 7 days with
      high urea alone. In contrast, with high NaCl alone, GPC:PDE activity reverts to
      control values by 7 days, by which time synthesis of GPC is increased, accounting
      for sustained GPC accumulation. Collectively, these data suggest that GPC
      accumulation in response to either high NaCl or urea occurs initially by
      inhibition of its degradation but that the effect of NaCl on degradation differs,
      in that it is transient, while that of urea is sustained.

PMID- 7631759
TI  - PAF mediates neutrophil adhesion to thrombin or TNF-stimulated endothelial cells
      under shear stress.
AB  - Platelet-activating factor (PAF) is known to modulate polymorphonuclear leukocyte
      (PMN) adhesion to endothelial cells cultured under static conditions and
      activated by thrombin. In contrast, there are no data on the role of PAF in PMN
      adhesion to cells exposed to flow conditions and activated by stimuli other than
      thrombin. Here we used the PAF receptor antagonist L-659,989 to evaluate PMN
      adhesion to human umbilical vein endothelial cells (HUVEC) in basal conditions or
      upon challenge with thrombin or tumor necrosis factor-alpha (TNF-alpha).
      Experiments were performed under dynamic flow using a parallel-plate flow chamber
      and a computer-based image analysis system. Rolling and adhesion of PMNs to
      endothelial cells significantly increased upon stimulation with thrombin.
      Thrombin-stimulated HUVEC also synthesized higher amounts of PAF than untreated
      cells. Pretreatment of PMNs with L-659,989 significantly reduced their rolling
      and adhesion to thrombin-activated HUVEC. Stimulation of HUVEC with TNF-alpha
      significantly increased the number of rolling and adherent PMNs as compared with
      untreated cells. Adhesion of PMNs to and migration across TNF-alpha-stimulated
      HUVEC were reduced by L-659,989, whereas cell rolling was unchanged. We conclude
      that PAF mediates leukocyte interaction under flow conditions with HUVEC
      activated by inflammatory stimuli.

PMID- 7631760
TI  - Possible contribution of long open state to noninactivating Ca2+ current in
      detrusor cells.
AB  - The whole cell patch-clamp technique was used to measure Ca2+ current in isolated
      smooth muscle cells from guinea pig urinary bladder. Noniactivating Ca2+ channel
      current was modeled incorporating the long open state of the Ca2+ channel. When
      inactivation was examined over a wide voltage range, a completely U-shaped curve
      was obtained. Lack of inactivation at +80 mV could be attributed to the long open
      state induced by large depolarization as well as to minimal Ca2+ influx and
      Ca(2+)-dependent inactivation. Activation parameters were obtained by comparing
      the amplitudes of conditioned (by +80 mV, 5 s) and unconditioned test potentials.
      With the use of the activation curve and the U-shaped inactivation curve, a
      noninactivating current that peaks around +20 mV was obtained. This current is
      composed of a so-called "window" current and a persistent current brought about
      by the long open state. Differences in the voltage dependence of the development
      of the long open state in various smooth muscles, as well as differences in the
      equilibrium constant between open and inactivated states, could underlie the
      different patterns of contractile behavior that characterize smooth muscles.

PMID- 7631761
TI  - Hepatic Na(+)-K(+)-ATPase enzyme activity correlates with polarized beta-subunit
      expression.
AB  - We have examined underlying causes for observations made in hepatocytes in which
      catalytic subunits of Na(+)-K(+)-ATPase are found both in bile canalicular
      (apical) and sinusoidal (basolateral) membrane domains, whereas functional
      activity is associated preferentially with sinusoidal membrane sites. In a series
      of parallel studies, we determined by both light and electron microscopy that
      Na(+)-K(+)-ATPase alpha-subunits were localized to both membrane domains of
      hepatocytes. With the use of purified liver plasma membrane subfractions, ouabain
      inhibition curves demonstrated similar inhibition constants (inhibition constant
      10(-5) M), and immunoblots using alpha 1-, alpha 2-, and alpha 3-polyclonal and
      monoclonal antibodies demonstrated antigenic sites predominantly for alpha 1 in
      both membrane fractions. Also, Northern blot hybridization analysis revealed only
      the alpha 1-isoform in hepatocytes. In contrast to the bipolar distribution of
      the alpha 1-subunit, the beta-subunit was identified only at the sinusoidal
      surface using fluorescence labeling with a monoclonal antibody. The beta 1
      isoform was demonstrated by Northern blot analysis and was present predominantly
      at the sinusoidal domain by immunoblotting with polyclonal antibodies. In
      addition to the bipolar distribution of alpha 1, immunoblotting of liver plasma
      membrane subfractions demonstrated a symmetrical distribution of fodrin, ankyrin,
      actin, and E-cadherin at both domains. These results suggest that functionally
      competent alpha/beta-complexes form at the sinusoidal domain, whereas only alpha
      1-subunits are present at the apical pole.

PMID- 7631763
TI  - Inhibition by polyunsaturated fatty acids of cell volume regulation and osmolyte
      fluxes in astrocytes.
AB  - The polyunsaturated fatty acids, arachidonic, linoleic, and linolenic acids, were
      potent blockers of regulatory volume decrease (RVD) and of the swelling-activated
      efflux of [3H]taurine, D-[3H]aspartate, [3H]inositol, and 125I (used as marker of
      Cl) from rat cerebellar astrocytes in culture. The monounsaturated oleic and
      ricinoleic acids and saturated fatty acids were ineffective. The amino acid and
      125I fluxes were similarly inhibited by fatty acids, whereas inositol release was
      less sensitive. Polyunsaturated fatty acids appear to directly affect RVD in
      trypsinized astrocytes as the inhibition was immediate and fully reversible.
      Blockers of the arachidonic acid metabolic pathways, indomethacin
      (cyclooxygenase), esculetin (lipoxygenases), and metyrapone (P-450
      monooxygenases), did not prevent the effect of arachidonic acid, suggesting that
      further metabolism is not required for displaying the effects of arachidonic acid
      on RVD and osmolyte fluxes. Some blockers of arachidonic acid metabolic pathways,
      such as nordihydroguaiaretic acid (lipoxygenases) and naphthoflavone (P-450
      monooxygenases), also exhibited marked inhibitory effects on RVD and on osmolyte
      fluxes. The predominant arachidonic acid metabolite in astrocytes, 12
      hydroxyeicosatetraenoic acid, did not affect RVD or osmolyte fluxes. These
      results suggest that arachidonic acid and other polyunsaturated fatty acids
      directly inhibit the permeability pathways correcting cell volume after swelling
      in cultured astrocytes.

PMID- 7631762
TI  - Effect of Mg2+ and ATP on depolarization-induced Ca2+ release in isolated triads.
AB  - The effect of different free Mg2+ and ATP concentrations on depolarization
      induced Ca2+ release in isolated skeletal muscle triadic vesicles was examined by
      simultaneously monitoring direct effects on ryanodine receptors from either
      isolated or coupled terminal cisternae. Free Mg2+ was increased to concentrations
      of 11-14 microM, 81 microM, 175-181 microM, and 1 mM while total ATP
      concentration was kept constant or MgATP concentration was kept constant. We
      observed the following. 1) Increasing MgATP reduces the measurable Ca2+ release
      from isolated vesicles by stimulating the Ca(2+)-ATPase in the terminal
      cisternae. 2) Half-maximal inhibition of functionally coupled ryanodine receptors
      during depolarization-induced Ca2+ release is observed at 1 mM Mg2+, whereas half
      maximal inhibition of the nondepolarized ryanodine receptor is seen at 75 microM
      Mg2+ at the same free ATP and MgATP concentrations. 3) Two separate time
      constants for Ca2+ release were obtained for nondepolarized ryanodine receptors
      with free Mg2+ at 14 microM and free ATP at 6.1 mM; this may represent triadic
      ryanodine receptors vs. isolated terminal cisternae ryanodine receptors.

PMID- 7631764
TI  - Cortisol feedback in adrenalectomized adult sheep.
AB  - These experiments tested the sensitivity of cortisol feedback on
      adrenocorticotropic hormone (ACTH) secretion in adult sheep. In series I, five
      bilaterally adrenalectomized (ADX) adult sheep were maintained on "low" (125
      micrograms/h) or "high" (500 micrograms/h) intravenous cortisol replacement, and
      dose-response curves were obtained with corticotropin-releasing factor (CRF) and
      arginine vasopressin (AVP). CRF caused incremental increases in plasma ACTH at
      the low but not the high dose of cortisol. AVP was similarly ineffective in
      stimulating ACTH at the high dose of cortisol. However, in series II, where ADX
      animals were again maintained on low or high cortisol infusions, a combined
      infusion of CRF and AVP was able to stimulate a robust ACTH response during both
      steroid replacement regimens. These studies demonstrate that the pituitary
      represents a major site of steroid feedback in the sheep, with a relatively small
      increase in the concentration of cortisol, within the normal unstressed
      physiological range, being able to inhibit ACTH secretion in response to
      exogenous CRF and AVP. However, under these conditions, inhibition of ACTH
      release can be overcome by the combined action of CRF and AVP. Further studies in
      series III, concerned with the nature of glucocorticoid inhibition of AVP
      release, demonstrate that whereas exposure to maximal cortisol levels (5,000
      micrograms/h) completely abolishes the ACTH response to severe hemorrhage (15
      ml/kg over 15 min), AVP release is maintained, suggesting that the system
      controlling AVP release during hemorrhagic stress is less sensitive to the
      negative influences of glucocorticoids than is the system controlling ACTH
      release.

PMID- 7631765
TI  - Pituitary adenylate cyclase-activating polypeptide: occurrence and relaxant
      effect in female genital tract.
AB  - The distribution, localization, and smooth muscle effects of pituitary adenylate
      cyclase-activating polypeptide (PACAP) were studied in the human female genital
      tract. The concentrations of PACAP-38 and PACAP-27 were measured by
      radioimmunoassays, and both peptides were found throughout the genital tract. The
      highest concentrations of PACAP-38 were detected in the ovary, the upper part of
      vagina, and the perineum. The concentrations of PACAP-27 were generally low, in
      some regions below the detection limit and in other regions 1 to 5% of the PACAP
      38 concentrations. Immunocytochemistry revealed that PACAP was located in
      delicate varicose nerve fibers that were most abundant in the internal cervical
      os, where they mainly seemed to innervate blood vessels and smooth muscle cells.
      PACAP-38 and PACAP-27 (10(-10)-10(-6) M) caused a concentration-dependent
      relaxation of the spontaneous activity of the nonvascular smooth muscle strips
      from fallopian tube and myometrium in vitro. Likewise, both peptides (10(-10)-10(
      6) M) caused relaxation of nonrepinephrine (10(-6) M)-precontracted
      intramyometrial arteries. No effect of the PACAP sequences, PACAP-(6-27), PACAP
      (16-38), and PACAP-(18-27), on fallopian tube was observed. The findings suggest
      a smooth muscle regulatory role of PACAP in the human female reproductive tract.

PMID- 7631766
TI  - Central adiposity and its metabolic correlates in obese adolescent girls.
AB  - To establish whether alterations in insulin action and secretion and their
      relationship to body fat distribution occur early in the course of developing
      obesity, we studied 14 obese adolescent girls [13.2 +/- 0.7 yr, body mass index
      (BMI) 32 +/- 1.4], 16 nonobese young women (24.0 +/- 0.6 yr, BMI 21.0 +/- 0.9).
      Insulin action was assessed by a sequential two-step (8 and 40 mU,m-2.min-1)
      euglycemic insulin clamp in combination with [1-13C]glucose and indirect
      calorimetry. Insulin secretion was determined by the hyperglycemic clamp
      technique (6.9 mmol/l). Magnetic resonance imaging was used to quantify visceral
      and subcutaneous abdominal fat depots. In obese girls, an impairment in glucose
      disposal was present with both insulin doses; at the higher dose, rates of
      glucose uptake were reduced by 30% in nonobese girls (240 +/- 30 vs. 340 +/- 19
      mg.m-2.min-1, P < 0.05) and by an additional 29% (170 +/- 17 mg.m-2.min-1, P <
      0.05) in obese girls. Insulin infusion failed to stimulate glucose oxidation and
      to suppress lipid oxidation only in obese girls. Suppression of free fatty acid
      levels, but not hepatic glucose production, was decreased in obese girls compared
      with controls. Fasting and glucose-stimulated insulin responses were greater in
      obese than in nonobese adolescents, who, in turn, had greater responses than lean
      women. In obese girls, visceral fat, but neither waist-to-hip circumference ratio
      nor subcutaneous fat, was highly correlated with basal insulin secretion (r =
      0.89, P < 0.001), stimulated insulin secretion (r = 0.61, P < 0.05), and insulin
      resistance (r = -0.87, P < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7631767
TI  - A model of skeletal muscle leucine kinetics measured across the human forearm.
AB  - We propose a new six-compartment model of intracellular muscle kinetics of
      leucine and of its transamination product alpha-ketoisocaproic acid (KIC) by
      combining systemic tracer infusions of [14C]- and [15N]leucine with the arterial
      deep venous catheterization of the human forearm. Venous [14C]KIC specific
      activity (SA) is taken as representative of intracellular [14C]leucine SA,
      whereas net [15N]leucine disposal is used to calculate leucine inflow and outflow
      across forearm cell membrane(s). In post-absorptive normal subjects, model
      derived rates of intracellular leucine release from and incorporation into
      protein were approximately 32% (P = 0.03) and approximately 37% greater (P =
      0.025), respectively, than those calculated using a conventional arteriovenous
      approach. Forearm fasting proteolysis exceeded protein synthesis (P < 0.025),
      whereas leucine oxidation was greater than zero (P < 0.01), suggesting a net
      negative leucine (i.e., protein) balance. Leucine inflow from blood to cell
      represented approximately 30% of arterial leucine delivery; therefore
      approximately 70% of arterial leucine bypassed intracellular metabolism. This
      model provides a comprehensive description of regional leucine and KIC kinetics
      and new estimates of protein degradation and synthesis across the human forearm.

PMID- 7631768
TI  - Effect of somatotropin and feed restriction on body composition and adipose
      metabolism in obese Zucker rats.
AB  - The objective of the present study was to determine whether exogenous
      somatotropin (STH) administration in conjunction with feed restriction could
      alter the composition of gain in the obese rat. Five-week-old female lean and
      obese Zucker rats were assigned to the following treatments for 6 wk: ad libitum
      fed (AL), restricted (approximately 75% of AL lean), and restricted with STH (2
      mg STH/day). Growth rate was decreased in restricted groups and was normalized to
      that of the AL lean group in restricted rats treated with STH. In lean rats,
      restriction decreased protein accretion. Restriction plus STH treatment decreased
      lipid accretion but increased protein accretion and body weight gain compared
      with the AL lean group. As expected, feed restriction reduced body size in obese
      rats, but carcass lipid was maintained at 44%, a level similar to that of the AL
      obese rats. Lipid accretion rate was decreased with restriction in obese rats and
      was further reduced, to a level similar to that of the lean group, in the obese
      rats that were restricted and treated with STH. Protein accretion was decreased
      in the restricted obese group but was normalized in those treated with STH to a
      level similar to that in the AL lean group. Basal rates of lipolysis in isolated
      adipocytes were not affected by STH. However, STH treatment normalized the
      responsiveness of cells from the obese rats to stimulation of lipolysis by
      isoproterenol. The results demonstrate that a combination of caloric restriction
      and STH was effective in normalizing body weight and composition of gain in the
      obese Zucker rat.

PMID- 7631769
TI  - Placental norepinephrine clearance: in vivo measurement and physiological role.
AB  - The intrauterine clearance rate of catecholamines is higher than in newborn
      animals or in adults. The separate contributions of the fetus and placenta to
      this clearance are not known. The placenta is a site of expression of the amine
      plasma membrane transporters that mediate this process. To determine the
      physiological role of this placental transporter in vivo, we studied fetal sheep
      at 123 days with common umbilical vein (UV), fetal arterial (AO), and venous
      catheters. Tritiated norepinephrine ([3H]NE) was infused to determine the
      kinetics of placental and fetal NE appearance and clearance rates. Umbilical flow
      was determined by [3H]NE infusion. Placental and total (fetal-placental) NE
      clearance rates were determined by measurement of [3H]NE from simultaneously
      drawn UV and AO samples. Total clearance was 99 +/- 8 ml.kg-1.min-1. Placental
      fractional [3H]NE extraction was 21% and accounted for 48% of total clearance.
      Fetal plasma NE production rate was 85 +/- 20 ng.kg-1.min-1. We conclude that
      placental catecholamine clearance is an important metabolic function of the
      placenta. This mechanism for clearance of the high fetal production rate of
      catecholamines is vital for fetal homeostasis. We speculate that derangements in
      placental catecholamine clearance may explain the exaggerated adverse effects on
      the fetus of drugs like cocaine, which block catecholamine transport.

PMID- 7631770
TI  - The insulin action-fiber type relationship in humans is muscle group specific.
AB  - The purpose of the present investigation was to determine the relationship
      between skeletal muscle characteristics, adiposity, and in vivo insulin action.
      Percutaneous muscle biopsies of the vastus lateralis (VL) and gastrocnemius (G)
      muscles were obtained from twenty-two sedentary male subjects. Insulin
      sensitivity (SI) and glucose effectiveness (SG) were determined from minimal
      model analysis, and indexes of regional and overall adiposity were obtained. SI
      was positively related to the citrate synthase activity from the VL (r = 0.50, P
      < 0.01) but unrelated to the citrate synthase activity from the G (r = 0.28).
      Similarly, SI was inversely related to the percentage of type IIb fibers in the
      VL (r = -0.47, P < 0.01) but unrelated to the percentage of type IIb fibers in
      the G (r = 0.06). SG was unrelated to fiber type, oxidative capacity, or
      adiposity. These data suggest that oxidative capacity and other characteristics
      related to VL skeletal muscle fiber type are determinants of in vivo insulin
      action but that this relationship cannot be extended to all muscle groups.
      Finally, neither skeletal muscle characteristics nor adiposity appears to be a
      determinant of SG in sedentary males.

PMID- 7631771
TI  - Kinetics of glucose delivery to subcutaneous tissue in rats measured with 0.3-mm
      amperometric microsensors.
AB  - The time between intravenous injection of a glucose bolus and the time the
      glucose concentration peaked in the subcutaneous tissue was measured in
      pentobarbital-anesthetized rats with implanted 290-microns-diameter amperometric
      sensors. Boluses of 100, 200, and 400 mg/kg body wt were injected. The glucose
      concentration in the jugular vein was monitored by frequent withdrawal and
      analysis of samples. The glucose concentration in the subcutaneous tissue was
      continuously monitored with the sensors. The times required for the
      subcutaneously implanted sensor to reach its maximum current, corrected for
      sensor response times, were 7.5 +/- 3.9, 9.8 +/- 5.5, and 10.0 +/- 4.4 min for
      the smallest to the largest dose, respectively. The shorter delay in response to
      the smallest dose was statistically significant (P < 0.03). The results were
      consistent with dilution of the bolus in the cardiovascular system and transport
      of glucose by both diffusion and facilitated transport via a saturable mediator.
      An understanding of the differences in the dynamics of venous vs. subcutaneous
      response to a glucose dose is important in developing algorithms for the control
      of blood glucose based on a subcutaneous measurement.

PMID- 7631772
TI  - Regulation of alpha 2-adrenergic receptor expression and signaling in pancreatic
      beta-cells.
AB  - Activation of alpha 2-adrenergic receptors (alpha 2-AR) in pancreatic beta-cells
      inhibits insulin secretion in response to various stimuli, and acute or long-term
      regulation of alpha 2-AR receptor-mediated effects may influence the tissue
      response to glucose dishomeostasis. As an initial approach to this issue, we
      determined the effect of various metabolic and hormonal treatments on alpha 2-AR
      expression and coupling in the pancreatic beta-cell lines HIT-T15 and RIN-5AH.
      Radioligand binding studies ([3H]RX-821002) and RNA blot analysis indicate that
      both pancreatic beta-cell lines express the alpha 2A/D-AR subtype [for HIT-T15
      the maximum binding (Bmax) = 113 +/- 28; for RIN-5AH Bmax = 93 +/- 18 fmol/mg of
      cellular protein]. Treatment of HIT-T15 or RIN-5AH cells with glucocorticoids
      [dexamethasone, hydrocortisone, or prednisolone (1 microM)] increased alpha 2-AR
      mRNA level and receptor protein density three- to fivefold. The glucocorticoid
      induced increase in receptor density in HIT-T15 cells was associated with 1) an
      increase in the amount of receptors coupled to G protein as determined by
      analysis of high-affinity 5'-guanylyl imidodiphosphate-sensitive binding of
      [3H]UK-14304, a selective alpha 2-AR agonist, and 2) a greater inhibition of
      forskolin-induced elevation of cellular adenosine 3',5'-cyclic monophosphate
      after receptor activation. Receptor density in HIT-T15 cells was not altered by
      different growth conditions, insulin (1 microM), phorbol 12-myristate 13-acetate
      (1 microM), or the sex steroids testosterone and progesterone (1 microM). These
      data indicate that glucocorticoids upregulate alpha 2-AR expression and signaling
      in pancreatic beta-cells. Such regulation may operate in a cell-specific manner,
      allowing discrete modulation of tissue responses to glucose dishomeostasis.

PMID- 7631773
TI  - Estimating energy expenditure from specific activity of urine urea during lengthy
      subcutaneous NaH14CO3 infusion.
AB  - Five healthy male subjects were continuously infused subcutaneously with
      [14C]bicarbonate (12.3 microCi/day) using a mini pump for 5 days while in a whole
      body calorimeter. Energy expenditure was varied over a range of 1.35-1.75 times
      basal metabolic rate. Urine collections were obtained throughout the study and
      used to measure the specific activity of urea, from which CO2 production was
      estimated. It was assumed that the recovery of label in gaseous CO2 was 95% of
      that infused and that the specific activity of urea was 85% that of expired CO2.
      Continuous daily collections of calorimeter air revealed that 95.6 +/- 1.3% (SD)
      of infused label was recovered as gaseous CO2, with little daily variation.
      Another 1.5 +/- 0.4% was recovered as urinary urea. The estimated CO2 production,
      calculated from the specific activity of urea in 24-h urine samples corrected for
      the small effects due to changes in the size and specific activity of the urea
      pool, was found to be 100 +/- 5% of the calorimeter estimate for 1-day periods
      (20.80 +/- 1.44 mol CO2/day) and 100 +/- 2% for 4-day periods. This study
      suggests that, in healthy subjects, the labeled [14C]bicarbonate-urea method can
      provide reasonable estimates of net CO2 production over the range examined.

PMID- 7631774
TI  - A limitation in the use of mass isotopomer distributions to measure
      gluconeogenesis in fasting humans.
AB  - The use of distributions of mass isotopomers in glucose from [U-13C]glycerol to
      estimate fractional rates of gluconeogenesis was examined. [U-13C]glycerol was
      infused into normal subjects who ingested acetaminophen and fasted for 60 h.
      Isotopomer distributions were measured by mass spectrometry in blood glucose and
      in glucuronic acid from urinary acetaminophen glucuronide. The distributions are
      incompatible with glucose production solely via gluconeogenesis from a single
      pool of triose phosphates. Rather, with the assumption of a single enriched
      triose phosphate pool, the distributions indicate, despite the 60 h of fasting,
      about as much glucose formation from an unlabeled glucose source as from that
      pool. Therefore the data indicate cellular heterogeneity in glycerol's
      metabolism, so that two or more pools with significantly different enrichments
      were the source of the glucose and glucuronic acid. This heterogeneity is related
      to much greater concentrations of glycerol in periportal than in pericentral
      zones of the liver lobule. Beyond evidence for heterogeneity, the findings
      emphasize a limitation in applying analyses of mass isotopomer distributions to
      measure polymer biosynthesis in the presence of heterogeneity in the precursor
      pool.

PMID- 7631775
TI  - Bicarbonate kinetics in humans: identification and validation of a three
      compartment model.
AB  - A model of bicarbonate kinetics is crucial to a correct interpretation of
      experiments for measuring oxidation in vivo of carbon-labeled compounds. The aim
      of this study is to develop a compartmental model of bicarbonate kinetics in
      humans from tracer data by devoting particular attention to model identification
      and validation. The data base consisted of impulse-dose studies of 14C-labeled
      bicarbonate in nine normal subjects. The decay curve of specific activity of CO2
      in expired air (saRCO2) was frequently sampled for 4-7 h. In addition, endogenous
      production of CO2, VCO2, was measured by indirect calorimetry. A model of data,
      i.e., an exponential model, analysis of decay curves of saRCO2 showed first that
      three compartments are necessary and sufficient to describe bicarbonate tracer
      kinetics. Compartmental models were then used as models of system. To correctly
      describe the input-output configuration, labeled CO2 flux in the expired air, phi
      RCO2 (= saRCO2.VCO2), has been used as measurement variable in tracer model
      identification. A mammillary three-compartment model with a respiratory and a
      nonrespiratory loss has been studied. Whereas there is good evidence that
      respiratory loss takes place in the central compartment, whether nonrespiratory
      loss is taking place in the central compartment or in one of the two peripheral
      compartments is uncertain. Thus three competing tracer models were considered.
      Using a model-independent analysis of data, based on the body activity variable,
      to calculate mean residence time in the system, we have been able to validate a
      specific model structure, i.e., with the two irreversible losses taking place in
      the central compartment. This validated tracer model was then used to quantitate
      bicarbonate masses in the system. Because there is uncertainty about where
      endogenous production enters the system, lower and upper bounds of masses of
      bicarbonate in the body are derived.

PMID- 7631776
TI  - A compartmental model of 3-methylhistidine metabolism in humans.
AB  - Urinary 3-methylhistidine (3MH) excretion has been proposed as a noninvasive in
      vivo marker of muscle protein breakdown, but such analysis requires quantitative
      collection of urine and yields few details about the metabolism of 3MH. In this
      study, we propose that data from a single bolus dose of tracer and serial blood
      samples over 72 h can be described by a kinetic model that defines 3MH metabolism
      in humans. Plasma concentration of the tracer was described by a linear time
      invariant three-compartment model. The model defines masses and fluxes of 3MH
      within the subjects and, in particular, the intracellular de novo production of
      3MH. The de novo production of 3MH as calculated by the model was not different
      from that calculated via the traditional collection of urinary 3MH (3.09 vs 2.57
      mumol.kg-1.day-1, respectively; P > 0.30). These data indicate that 3MH
      production can be measured by a compartmental model that can be used to measure
      muscle proteolysis without quantitative urine collections.

PMID- 7631777
TI  - Increased concentrations of glycogen synthase protein in skeletal muscle of
      patients with NIDDM.
AB  - To examine whether changes in the glycogen synthase protein concentration
      contribute to impaired insulin-stimulated glycogen metabolism in patients with
      noninsulin-dependent diabetes mellitus (NIDDM), muscle biopsies were taken before
      and after a 4-h euglycemic hyperinsulinemic clamp to measure glycogen synthase
      activity and glycogen synthase protein concentrations in 14 patients with NIDDM
      and in 17 control subjects. Nonoxidative glucose metabolism was reduced by 64% in
      patients with NIDDM compared with control subjects and correlated with insulin
      stimulated glycogen synthase activity (r = 0.55, P < 0.05). The concentration of
      glycogen synthase protein in skeletal muscle was higher in patients with NIDDM
      than in control subjects (6.75 +/- 0.88 vs. 4.41 +/- 0.50 counts.min-1.micrograms
      protein-1, P < 0.05), whereas there was no significant difference in glycogen
      synthase mRNA concentration between the two groups. The glycogen synthase protein
      concentration correlated inversely with the rate of nonoxidative glucose
      metabolism (r = -0.63, P < 0.05). These findings indicate that the amount of
      glycogen synthase protein is increased in skeletal muscle of patients with NIDDM.
      The increase in the glycogen synthase protein may serve to compensate for a
      functional defect in the activation of the enzyme by insulin.

PMID- 7631778
TI  - Responses of immunoreactive ACTH and bioactive ACTH to large hemorrhage and
      resuscitation in conscious dogs.
AB  - We studied the effect of fluid resuscitation on immunoreactive
      adrenocorticotropic hormone (irACTH) and bioactive ACTH (bioACTH) after
      hemorrhage in conscious dogs. Animals (n = 7) were bled 30% (approximately 25
      ml/kg) over 3 min and 30 min later were either resuscitated [43.3 ml/kg 0.9% NaCl
      (1.8 times hemorrhage volume) over 10 min] or not. Blood was reinfused after 210
      min. Animals had both treatments (> 4 days apart). irACTH, bioACTH, cortisol,
      angiotensin II, and aldosterone increased rapidly after hemorrhage. Resuscitation
      increased blood volume and cardiac output to resting values, but arterial
      hypotension persisted. bioACTH and irACTH decreased 40-90 min after hemorrhage in
      both groups, but each decreased more rapidly after resuscitation. The elimination
      half-life of bioACTH was shorter than that of irACTH, but neither was affected by
      resuscitation. The ratio of bioACTH to irACTH followed the same pattern with or
      without resuscitation. Angiotensin II and aldosterone remained increased without
      resuscitation but decreased promptly after resuscitation. In conclusion, 1)
      saline infusion at 1.8 x hemorrhage volume provides effective cardiovascular
      resuscitation, with resolution of hormonal responses to hemorrhage; 2) although
      ACTH responses resolved with or without resuscitation, resuscitation produced
      more rapid resolution without changing the parameters of ACTH elimination; 3) the
      dynamics of the resolution of the ACTH response to hemorrhage are similar whether
      induced by stimulus removal or feedback inhibition.

PMID- 7631779
TI  - Arginine enhances glycogen synthesis in response to insulin in 3T3-L1 adipocytes.
AB  - The present study was undertaken to define the role of L-arginine (L-Arg) in
      glucose metabolism in differentiated 3T3-L1 adipocytes in culture. L-Arg alone
      had no effect on 2-deoxyglucose uptake or basal glycogen synthesis, but this
      amino acid increased by 153 +/- 10% (P < 0.01) the incorporation of glucose into
      glycogen in insulin-treated cells. L-Glutamate (L-Glu), a major metabolite of L
      Arg, also enhanced insulin-stimulated glycogen synthesis. The response to insulin
      was not altered by L-lysine (L-Lys), but the effect of L-Arg was markedly
      attenuated by L-Lys. Cell incubation with L-Arg markedly enhanced arginase
      mediated urea synthesis, whereas L-Lys abolished this response. The stimulatory
      effect of L-Arg on insulin-stimulated glycogen synthesis did not appear to be
      accounted for by the generation of polyamines or the production of nitric oxide,
      both potentially derived from the enzymatic conversion of L-Arg. In the presence
      of insulin, cellular ATP levels were significantly increased by L-Arg, L-Glu, and
      L-Lys as well. These data suggest that metabolic degradation of L-Arg not related
      to citric acid cycle activity is important in the mechanism by which L-Arg
      enhances insulin-stimulated glycogen synthesis.

PMID- 7631780
TI  - Model of extreme hypoglycemia in dogs made ketotic with (R,S)-1,3-butanediol
      acetoacetate esters.
AB  - The rationale behind this study is that controlled starvation of poorly
      differentiated (anaplastic) fast-growing tumor cells, but not host cells, might
      be possible in vivo. The energy metabolism of anaplastic tumor cells, but not
      host cells, is largely dependent on carbohydrate metabolism at all times.
      Therefore depleting plasma of carbohydrate fuels could place these tumor cells at
      a significant metabolic disadvantage. Hence an animal model was developed in
      which all cells would be required to oxidize fatty acids, ketoacids, and/or 1,3
      butanediol to satisfy their energy needs. To achieve this aim, one would need
      ketosis, severe hypoglycemia, and low lactatemia. Anesthetized normal dogs were
      infused with somatostatin and a mixture of (R,S)-1,3-butanediol monoacetoacetate
      and (R,S)-1,3-butanediol diacetoacetate; these latter compounds are nonionized
      precursors of ketoacids. They were infused at 90% of the dog's caloric
      requirement. After establishment of a moderate ketosis (2-3 mM) over < 100 min, a
      severe degree of hypoglycemia (close to 0.5 mM) without rebound and without
      hyperlactatemia was induced by infusing insulin and dichloroacetate. Tracer
      kinetic measurements showed 1) a 20% decrease in the rate of appearance of
      glucose, 2) 50 and 62% increases in glycerol and nonesterified fatty acid rates
      of appearance, reflecting stimulation of lipolysis, and 3) no change in the rate
      of glutamine appearance. We suggest that this model may prove useful for
      selectively starving those cancer cells that are unable to utilize fat-derived
      fuels while preserving nutrient supply to vital organs.

PMID- 7631781
TI  - Role of prolactin and gonadal steroids in regulation of oxytocin mRNA during
      lactation.
AB  - The role of suckling, prolactin, and gonadal steroids in regulating hypothalamic
      oxytocin (OT) mRNA content during the 1st and 2nd wk of lactation was evaluated.
      On day 4 of lactation, OT mRNA content decreased in rats removed from their
      litter for 24 h compared with suckled controls. Either suckling (in the absence
      of prolactin release) or prolactin (in the absence of suckling) maintained OT
      mRNA content at this stage of lactation. In contrast, at day 11 of lactation, OT
      mRNA content remained unchanged in rats deprived of pups for 24 h. Ovariectomy
      did not compromise the ability of day 11 nonsuckled rats to maintain OT mRNA
      content; however, the increased water intake, plasma prolactin, plasma
      vasopressin (VP), plasma renin concentration, and hypothalamic VP mRNA content at
      day 11 compared with day 4 suggest a role for fluid balance in determining OT
      mRNA content during the 2nd wk of lactation. Thus, at day 4, suckling is a major
      determinant of OT mRNA content as a result of both direct activation of neuronal
      afferents to the OT neurons and stimulation of prolactin release. This is in
      contrast to day 11, when fluid balance may predominate in regulation of OT mRNA.

PMID- 7631782
TI  - Melatonin inhibition of GnRH-induced LH release from neonatal rat gonadotroph:
      involvement of Ca2+ not cAMP.
AB  - Melatonin inhibits gonadotropin-releasing hormone-induced release of luteinizing
      hormone (LH) from the neonatal rat gonadotrophs. The second messenger involved is
      not known, although there are several candidates, including adenosine 3',5'
      cyclic monophosphate (cAMP) and intracellular free Ca2+. The present study
      addresses the question of which second messenger mediates melatonin inhibition of
      LH release. We found that the effect of melatonin was not prevented by cAMP
      protagonists, including 8-bromo-cAMP, dibutyryl cAMP, 3-isobutyl-1
      methylxanthine, and forskolin. However, treatments that enhanced Ca2+ influx
      masked the effects of melatonin, and treatments that blocked Ca2+ influx mimicked
      the effects of melatonin. Moreover, melatonin decreased K(+)-induced LH release,
      which is dependent on Ca2+ influx but did not block release of LH due to
      thapsigargin-induced mobilization of Ca2+ from intracellular stores. These
      findings indicate that melatonin inhibits gonadotropin-releasing hormone-induced
      LH release, primarily through an action involving inhibition of Ca2+ influx, and
      that cAMP does not seem to be involved in this effect of melatonin.

PMID- 7631783
TI  - Marked resistance of RAR gamma-deficient mice to the toxic effects of retinoic
      acid.
AB  - Excessive intake of retinol or of retinoic acid causes a syndrome of
      characteristic toxic effects known as hypervitaminosis A. To test the role of the
      nuclear retinoic acid receptor (RAR gamma) in this process we produced mice with
      a targeted disruption of the RAR gamma gene and examined toxic effects of
      repeated doses of retinoic acid and two other synthetic retinoids, Ro 15-1570 and
      Ro 40-6055. Surprisingly, homozygous mutant mice were resistant to fourfold
      higher doses of retinoic acid than wild-type mice as well as to elevated doses of
      the synthetic retinoids, indicating that RAR gamma may have a major role in
      mediating retinoid toxicity, a finding that possibly has practical implications
      for reducing the toxicity of synthetic retinoids in clinical use.

PMID- 7631784
TI  - Regulation of cholesteryl ester transfer activity in adipose tissue: comparison
      between hamster and rat species.
AB  - The present study demonstrates cholesteryl ester transfer activity (CETA) in
      cultured hamster and rat adipose tissue. Cultured hamster and rat adipose tissue
      fragments released CETA into the conditioned medium, and this was associated with
      a reciprocal decrease in adipose tissue CETA. Regional variations in adipose CETA
      were observed. The levels of CETA released from cultured hamster and rat
      adipocytes were higher than those from adipose tissue fragments. In hamsters but
      not in rats, the secretion of CETA from cultured adipose tissue was increased by
      insulin and inhibited by EDTA in a dose-dependent fashion. Monoclonal antibodies
      against human cholesteryl ester transfer protein inhibited the CETA secreted from
      hamster adipose tissue but not that from rat adipose tissue. Fasting for 24 h and
      a high-cholesterol saturated fat-rich diet increased adipose CETA in hamsters and
      rats, and this was associated with an elevation of plasma CETA only in hamsters.
      This supports the view that, in hamsters, adipose CETA has in situ and
      intravascular functions, whereas in rats the role of adipose CETA is restricted
      to tissue-specific functions. Hamster cholesteryl ester transfer protein may
      differ from rat adipose-associated CETA in the structure of the active site and
      the regulatory mechanism for its secretion.

PMID- 7631785
TI  - Mammalian Na+/H+ exchanger gene family: structure and function studies.
AB  - Na+/H+ exchangers are integral plasma membrane proteins that exchange
      extracellular Na+ for intracellular H+ with a stoichiometry of one for one. They
      are inhibitable by the diuretic amiloride and have multiple cellular functions,
      including intracellular pH homeostasis, cell volume control, and electroneutral
      NaCl absorption in epithelia. The presence of multiple forms of the exchangers
      was demonstrated by the recent cloning of four mammalian Na+/H+ exchangers, NHE1,
      NHE2, NHE3, and NHE4. All of these cloned Na+/H+ exchangers have 10-12 putative
      transmembrane helixes and a long cytoplasmic carboxyl domain. Despite the
      structural similarity, these Na+/H+ exchanger isoforms differ in their tissue
      distribution, kinetic characteristics, and response to external stimuli. The
      present review deals with the recent developments in the molecular identification
      of the Na+/H+ exchanger gene family, the functional characteristics, and the
      short-term regulation of Na+/H+ exchange at molecular and cellular levels.

PMID- 7631786
TI  - Chronic renal failure increases cytosolic Ca2+ of hepatocytes.
AB  - Chronic renal failure (CRF) is associated with increased Ca2+ content of liver
      and reduced hepatic lipase activity. This has been attributed to a rise in
      cytosolic Ca2+ ([Ca2+]i) of the hepatocytes, but data on this issue are lacking.
      We examined the [Ca2+]i and ATP content of hepatocytes as well as the activity of
      Na(+)-K(+)-adenosinetriphosphatase (Na(+)-K(+)-ATPase), Ca(2+)-ATPase, and
      Na+/Ca2+ exchanger of hepatic membrane vesicles from normal rats, animals with 6
      wk of CRF, CRF normocalcemic parathyroidectomized (CRF-PTX) rats, and CRF and
      normal animals treated with verapamil (CRF-V, normal-V). [Ca2+]i in hepatocytes
      of CRF rats was higher (281 +/- 7.4 nM) and ATP lower (6.4 +/- 1.8 nmol/mg
      protein) than in normal (209 +/- 5.3 nM; 12.5 +/- 0.89 nmol/mg protein), CRF-PTX
      (212 +/- 1.0 nM; 13.7 +/- 0.79 nmol/mg protein), normal-V (215 +/- 2.3 nM; 14.2
      +/- 0.77 nmol/mg protein), and CRF-V rats (209 +/- 7.4 nM; 14.8 +/- 0.72
      nmol/10(6) cells). The Na(+)-K(+)-ATPase, the maximal velocity of Ca(2+)-ATPase,
      and the activity of the Na+/Ca2+ exchanger were reduced, whereas the Michaelis
      constant of Ca(2+)-ATPase was increase in CRF rats compared with the other four
      groups of rats. The values in the latter groups were not different.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7631787
TI  - Somatostatin inhibits secretin-induced ductal hypercholeresis and exocytosis by
      cholangiocytes.
AB  - Previous work from our laboratory has implicated hormone-induced plasma membrane
      movement (i.e., endo- and exocytosis) in water and electrolyte transport by the
      epithelial cells that line the ducts in the liver (i.e., cholangiocytes). To
      further explore the cellular mechanisms regulating ductal bile secretion, we
      infused somatostatin and/or secretin intravenously into rats 2 wk after either
      bile duct ligation (BDL), a procedure that induces selective proliferation of
      cholangiocytes, or sham surgery and measured bile flow and biliary constituents.
      We also determined the effect of somatostatin on basal and secretin-induced
      exocytosis by purified cholangiocytes isolated from rat liver after BDL. Finally,
      we studied the expression of the somatostatin receptor gene by both ribonuclease
      (RNase) protection and nuclear run-on assays using cDNA encoding for two subtypes
      of the somatostatin receptor gene (i.e., SSTR1 and SSTR2). In vivo, somatostatin
      infusion caused a dose-dependent bicarbonate-poor decrease (57% maximal decrease
      below baseline; P < 0.05) in bile flow in BDL but not in sham-operated rats; in
      contrast, secretin caused a dose-dependent bicarbonate-rich choleresis (228%
      maximal increase above baseline; P < 0.05) in BDL but not in sham-operated rats.
      Simultaneous or prior infusion of somatostatin inhibited the secretin-induced
      hypercholeresis in BDL rats. In vitro, somatostatin had no effect on basal
      exocytosis by cholangiocytes isolated from BDL rats; however, somatostatin
      inhitibed (88% maximal inhibition; P < 0.05) secretin-induced exocytosis by
      cholangiocytes in a dose-dependent fashion. In addition, somatostatin inhibited
      secretin-induced increases in levels of adenosine 3',5'-cyclic monophosphate
      (cAMP) in cholangiocytes isolated from BDL rats.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7631788
TI  - Reactivation of hapten-induced colitis and its prevention by anti-inflammatory
      drugs.
AB  - Administration of a hapten together with a barrier breaker, such as ethanol, into
      the colon of a rat results in extensive mucosal injury and inflammation that
      bears some similarity to the colonic inflammation characterizing inflammatory
      bowel disease in humans. This inflammation and injury gradually subsides over the
      weeks after its induction. We have attempted to determine whether this colitis
      can be "reactivated" by administration of the hapten systemically weeks after its
      initial intracolonic administration. Six weeks after intracolonic administration
      of trinitrobenzene sulfonic acid (the hapten) in a vehicle of 50% ethanol, most
      of the colonic injury and inflammation had subsided. Intravenous administration
      of the hapten at 24-h intervals over 3 days resulted in reactivation of the
      colitis, with significant increases in macroscopic and histological damage scores
      (mucosal injury and inflammation) and a significant increase in granulocyte
      infiltration, as measured by tissue myeloperoxidase (MPO) infiltration, as
      measured by tissue myeloperoxidase (MPO) activity. The increase in MPO activity
      occurred only in the region previously exposed to the hapten. Intravenous
      administration of saline did not reactivate the colitis, nor did intravenous
      administration of the hapten to rats previously treated intracolonically with
      saline or the ethanol vehicle. Reactivation of colitis by hapten administration
      was not accompanied by activation of mucosal mast cells. Treatment with
      dexamethasone prevented the increase in colonic damage score and MPO activity
      elicited by intravenous hapten administration. Cyclosporin A reduced MPO
      activity, and 5-aminosalicylic acid reduced the colonic damage score, whereas
      lidocaine and two inhibitors of leukotriene synthesis did not significantly
      affect either of these parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7631789
TI  - Somatostatin excites canine ileum ex vivo: role for nitric oxide?
AB  - Isolated perfused segments of canine ileum have no spontaneous motor activity and
      release large quantities of vasoactive intestinal polypeptide (VIP) continuously.
      Somatostatin perfusion was shown to decrease VIP release, accompanied by
      increased contractions and amplification of responses to low-frequency electrical
      field stimulation. After perfusion of higher somatostatin concentrations, the VIP
      output did not recover but quiescence returned. The actions of somatostatin on
      motor activity were not modified by hexamethonium, slightly reduced by atropine,
      and markedly reduced by tetrodotoxin. Inhibition of VIP output was not the major
      determinant of motor activity in the ileum because 1) a second infusion of
      somatostatin had similar motor effects despite markedly reduced VIP output, 2)
      abolition of tonic VIP output did not prevent induction of motor activity by
      somatostatin, and 3) artificial restoration of VIP levels did not prevent or
      antagonize somatostatin-induced ileal contractions. In contrast, the increment in
      motor responses induced by somatostatin was not apparent after N omega-nitro-L
      arginine methyl ester, an inhibitor of nitric oxide (NO) synthase, but recovered
      after reversal by L-arginine. We conclude that the mode of somatostatin
      activation of intestinal motor activity involves reduced NO output, enhanced
      excitatory mediator action or release, a direct action on smooth muscle, and
      possibly inhibition of VIP output. Of these, reduced NO output plays the most
      important role.

PMID- 7631791
TI  - Dual effect of deferoxamine on free radical formation and reoxygenation injury in
      isolated hepatocytes.
AB  - The effects of low concentrations (10 and 100 microM) and high concentrations (1,
      10, and 20 mM) of deferoxamine (DFO) on superoxide (O2-.) formation, lipid
      peroxidation, and cell injury were studied in freshly isolated perfused rat
      hepatocytes during a 2-h reoxygenation period after 2.5 h of anoxia. O2-.
      production was measured by lucigenin-enhanced chemiluminescence, lipid
      peroxidation by malondialdehyde (MDA) formation, and cell injury by lactate
      dehydrogenase (LDH) release. On reoxygenation and in the absence of DFO, O2-.
      generation increased 11-fold, MDA increased 3.7-fold, and LDH release practically
      doubled. Low concentrations of DFO had no effect on O2-. generation but decreased
      MDA and LDH release from 44 to 75%. High concentrations of DFO significantly
      depressed O2-. formation, with very little additional effect on MDA or LDH
      release. These experiments illustrate in a biological system the dual effect of
      DFO: 1) at low Concentrations, DFO acts as a specific iron chelator and inhibits
      lipid peroxidation and cell injury without preventing O2-. formation, and 2) at
      high concentrations, DFO acts as a nonspecific scavenger of oxygen free radicals
      such as O2-.

PMID- 7631790
TI  - Cellular and regional expression of transcripts of the plasma membrane calcium
      pump PMCA1 in rabbit intestine.
AB  - The plasma membrane Ca(2+)-pumping adenosinetriphosphatase (PMCA) is the energy
      dependent step in the active vitamin D-dependent absorption of dietary Ca2+ by
      the enterocyte. Studies of the various PMCA genes and splicing variants in humans
      and rats have indicated that the isoform known as PMCA1b is the predominant form
      expressed in small intestine. Using an oligonucleotide probe, we have studied the
      regional and cellular distribution of PMCA1 transcripts in rabbit intestinal
      tissues by in situ hybridization. On small intestinal RNA blots, this hybridized
      to species similar in size to those detected by PMCA1-specific cDNA probes; an
      additional larger transcript was present in rabbit than in rat or human. In situ
      hybridization signals were principally in the enterocyte population of the mucosa
      and were maximal in differentiating enterocytes on the lower part of the villus,
      a pattern similar to that previously demonstrated for other nutrient
      transporters. Reflecting the capacity of the different small intestinal segments
      to transport Ca2+, much higher levels of transcript were detected by both methods
      proximally (in duodenum) than distally (in jejunum and ileum) and were also
      higher in cecum and ascending colon mucosa than in descending colon. We conclude
      that as enterocytes differentiate in regions that absorb Ca2+, they express high
      levels of mRNA for PMCA1. These results confirm the importance of transcriptional
      regulation of this gene for active Ca2+ absorption.

PMID- 7631792
TI  - Effects of cerebral TRH on intestinal water transport: role of vagal, muscarinic,
      and VIP pathways.
AB  - Thyrotropin-releasing hormone (TRH) is a central nervous system (CNS) transmitter
      that stimulates various gastrointestinal secretory and motor processes by
      increasing vagal outflow. In this study, the CNS effects of TRH on ileal and
      jejunal water transport were examined in awake rats and dogs, respectively.
      Cerebral but not intravenous TRH (0.1-5.0 nmol/kg) significantly (P < 0.01)
      reversed net water absorption from approximately 30 microliters.cm-1.h-1 in rats
      and 300 microliters.cm-1.h-1 in dogs toward net water secretion of 60 and 600
      microliters.cm-1.h-1, respectively. Truncal vagotomy and ganglionic blockade with
      chlorisondamine completely abolished this stimulatory effect of cerebral TRH,
      whereas adrenalectomy, hypophysectomy, noradrenergic and opiate blockade, and
      inhibition of prostaglandin and nitric oxide synthesis did not. Atropine
      methylnitrate significantly (P < 0.05) attenuated the stimulatory response
      produced by TRH by approximately 30%. Intravenous infusion of the vasoactive
      intestinal peptide (VIP) receptor antagonist, [4Cl-D-Phe6, Leu17]VIP (0.05-5.0
      mumol.kg-1.h-1), significantly (P < 0.01) inhibited the stimulatory response of
      TRH by approximately 60%. Pretreatment of the animals with both atropine and the
      VIP antagonist completely abolished ileal and jejunal water secretion stimulated
      by cerebral TRH. These results indicate that 1) TRH acts within the CNS to
      stimulate net ileal and jejunal water secretion in rats and dogs, respectively;
      2) these actions are mediated by vagal pathways; and 3) stimulation of intestinal
      secretion by cerebral TRH is primarily mediated by a VIP-sensitive mechanism and,
      in part, by a muscarinic mechanism.

PMID- 7631793
TI  - Role of the intestine in chylomicron remnant clearance.
AB  - When 810 mumol of [3H]glyceryl trioleate (TO) were infused intraduodenally over 6
      h into rats, 29% of the triacylglycerol (TG) acyl groups in the mucosa were not
      from the infusate. We tested the hypothesis that chylomicron remnants contribute
      to the mucosal pool of nondietary TG acyl groups, since the acyl group
      composition of the chylomicron remnants was 58% oleate, compared with 90% in
      their parent chylomicrons. Purified 3H-labeled remnants were generated from
      chylomicrons formed in rats receiving TO intraduodenally, with 95% of the remnant
      disintegrations per minute (dpm) being in TG. The 3H-remnants were infused
      intravenously into rats receiving either saline or 135 mumol/h TO
      intraduodenally. In the saline-infused rats, 32% of the infused 3H dpm were in
      the proximal and 19% in the distal intestine and 32% were in the liver. In the
      fat-infused rats, 12% of the infused 3H dpm were in the proximal and 5% were in
      the distal gut and 29% were in the liver. When [3H]cholesterol-labeled remnants
      were infused intravenously and saline was infused intraduodenally, the percentage
      uptake into the mucosa was nearly the same as with the TG label, but comparable
      uptake by the liver increased. We conclude that the intestine competes with the
      liver for chylomicron remnant TG and cholesterol.

PMID- 7631794
TI  - Effect of orthotopic transplantation of liver on systemic and splanchnic
      hemodynamics in conscious rat.
AB  - The long-term cardiovascular effects of orthotopic liver transplantation (OLT)
      were studied in conscious Lewis rats with a radioactive microsphere technique.
      Three months after OLT with an all-suture technique for graft revascularization
      (s-OLT), all hemodynamic parameters were similar to control. OLT with "cuffs"
      fitted to the portal vein and infrahepatic inferior vena cava (c-OLT) led to
      prominent hemodynamic disturbances including 1) hyperkinetic circulation with
      increased cardiac index (CI; 22%; P < 0.05) and decreased mean arterial pressure
      (15%; P < 0.05) and total peripheral resistance (TPR; 28%; P < 0.05); 2) a slight
      increase in portal pressure (11.8 +/- 0.9 vs. 9.3 +/- 1.7 mmHg in control) and
      marked portal-systemic shunting (51 +/- 11 vs. 0.05 +/- 0.04% in control; P <
      0.05); 3) increased hepatic arterial blood flow (0.49 +/- 0.06 vs. 0.27 +/- 0.04
      ml.min-1.g liver wt-1; P < 0.05); 4) splanchnic vasodilation with vascular
      resistance significantly (P < 0.05) lower in the liver, stomach, and large
      intestine; and 5) increased blood flow and decreased vascular resistance in the
      kidneys and heart. Ganglionic blockade with chlorisondamine (5 mg/kg body wt iv)
      indicated that the increase in CI seen in the c-OLT rats was probably
      sympathetically mediated, whereas the increase in renal blood flow was a
      reflection of the increase in CI. After ganglionic blocker administration, TPR
      and regional vascular resistances decreased to approximately the same extent in
      the control and c-OLT groups, indicating that vascular sympathetic tone was
      unchanged in the c-OLT rats.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7631795
TI  - Somatostatin inhibits AP-1 function via multiple protein phosphatases.
AB  - We have reported previously that the widespread inhibitory actions of
      somatostatin might be mediated by its ability to inhibit the expression of the
      immediate early genes c-fos and c-jun. The products of these genes form a
      heterodimeric transcription factor complex [activator protein 1 (AP-1)], which is
      known to be induced by treatment with phorbol esters. In the present study, we
      sought to investigate the mechanisms by which somatostatin inhibits immediate
      early gene expression. For our experiments, we used a rat pituitary adenoma cell
      line (GH3), which is known to express multiple subclasses of somatostatin
      receptors. The phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA)
      stimulated both AP-1 binding and transcriptional activity in GH3 cells and the
      somatostatin analogue octreotide inhibited this response by 40-70%. In the
      presence of two different phosphatase inhibitors, sodium orthovanadate or okadaic
      acid, the ability of somatostatin to inhibit AP-1 binding and transcriptional
      activity was abolished. This effect of octreotide, which appears to be mediated
      by the SSTR2 and SSTR5 subtypes of somatostatin receptors, was paralleled by its
      ability to inhibit TPA-stimulated GH3 cell proliferation. Pretreatment of the GH3
      cells with pertussis toxin (200 ng/ml) reversed the inhibitory effect of
      octreotide on both AP-1 function and cellular proliferation. Our observations
      lead us to conclude that somatostatin not only inhibits immediate early gene
      expression but also inhibits AP-1 binding and transcriptional activity via the
      action of several classes of protein phosphatases. This effect, which is
      pertussis toxin sensitive, might be one mechanism by which somatostatin inhibits
      cellular proliferation.

PMID- 7631796
TI  - Ca2+ waves are organized among hepatocytes in the intact organ.
AB  - Hormone-induced increases in cytosolic Ca2+ (Cai2+) begin as Cai2+ waves in cells
      isolated from most types of tissue (1, 11), but whether such waves actually occur
      in vivo is unknown. To investigate this, we examined vasopressin-induced Cai2+
      signals in hepatocytes within the perfused rat liver. Using confocal fluorescence
      video microscopy, we found that increases in Cai2+ began as waves that usually
      originated in hepatocytes near central venules, then spread opposite to the
      direction of blood flow, to hepatocytes near portal venules. We used
      immunochemistry to determine that the liver vasopressin V1a receptor is most
      concentrated among hepatocytes in the pericentral region, providing the mechanism
      by which Cai2+ waves originate there. Pericentral-to-periportal Cai2+ waves may
      direct peristaltic flow of bile, since Cai2+ induces contraction of the apical
      pole of hepatocytes and since peristaltic contractions in liver also occur in a
      pericentral-to-periportal direction. The organization of Cai2+ waves among cells
      in intact tissue may be a means by which an integrative, organ-level response is
      provided in response to hormonal stimuli.

PMID- 7631797
TI  - Mechanism of action of somatostatin on the canine ileal circular muscle.
AB  - The aim of this study was to investigate the mechanism of action of somatostatin
      on the circular muscle of the isolated canine ileum using the microelectrode
      technique. The membrane potential from circular muscle cells was recorded in two
      preparations: 1) whole thickness circular and longitudinal muscle (with intact
      myenteric and deep muscular plexuses, n = 13) and 2) isolated circular muscle
      (with only deep muscular plexus, n = 9). In this preparation, inhibitory junction
      potentials (IJPs), elicited after field stimulation, are mediated by a nitric
      oxide-related (NO-R) compound. Somatostatin (10(-6) M) transiently (2-5 min)
      depolarized the circular muscle cells in both whole thickness (3.6 +/- 1.0 mV, P
      < 0.01) and isolated circular muscle preparations (8.0 +/- 0.8 mV, P < 0.01).
      Somatostatin did not reduce either the amplitude or duration of the IJP in the
      isolated circular muscle but reduced slow-wave amplitude. In contrast, a
      reduction (20-50%) in the amplitude of the IJP was observed in the whole
      thickness preparation, and there was little effect on slow-wave amplitude.
      Somatostatin did not affect the induced slow wave observed in the whole thickness
      preparation after field stimulation. Apamin significantly reduced the amplitude
      of the IJP in both preparations. Somatostatin (10(-6) M) did not modify the
      apamin-resistant IJP. A reduction in the slow-wave amplitude was observed in the
      isolated circular muscle preparation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7631798
TI  - Hepatorenal baroreflex in cirrhotic rats.
AB  - A hepatorenal baroreflex has been described in which increases in intrahepatic
      sinusoidal pressure stimulate an intrahepatic baroreceptor, resulting in
      increases in afferent hepatic (HNA) and efferent renal sympathetic nerve activity
      (RNA). Hepatic denervation prevents the increase in RNA. This baroreflex is
      postulated to contribute to the increase in RNA found in cirrhosis in which
      intrahepatic sinusoidal pressure is increased. However, the increased fibrosis in
      the cirrhotic liver may render the intrahepatic baroreceptor less sensitive to
      increases in intrahepatic sinusoidal pressure. By use of thoracic inferior vena
      caval constriction, intrahepatic sinusoidal pressure (i.e., inferior vena caval
      pressure, IVCP) was increased in control rats and rats with cirrhosis due to
      common bile duct ligation (CBDL) while HNA and RNA were measured. With increases
      in IVCP of 5 mmHg, increases in HNA (+38 +/- 2 and +44 +/- 3%) and RNA (+25 +/- 1
      and +34 +/- 3%) were not different in control and CBDL rats, respectively. The
      slope gain, % delta HNA/delta IVCP, was +7.1 +/- 0.6 and +8.1 +/- 0.7%/mmHg in
      control and CBDL rats, respectively. Therefore the hepatorenal baroreflex is not
      desensitized in the CBDL rat, and the hepatorenal baroreflex is capable of
      contributing to the increase in RNA observed in cirrhosis.

PMID- 7631799
TI  - Excess nitric oxide does not cause cellular, vascular, or mucosal dysfunction in
      the cat small intestine.
AB  - The overproduction of nitric oxide in the small bowel has been invoked as a
      cytotoxic event in the vascular, mucosal, and whole organ dysfunction associated
      with inflammation. We assessed whether exogenous administration of nitric oxide
      in the form of nitric oxide donors (CAS 754, SIN-1) could cause microvascular and
      mucosal barrier dysfunction in vivo or epithelial and endothelial cell
      permeability alterations and cell injury in vitro. Increasing concentrations of
      CAS 754 or SIN-1 were infused locally into autoperfused segments of cat ileum at
      30-min intervals. Baseline epithelial permeability (blood-to-lumen clearance of
      51Cr-EDTA) was not affected by CAS 754, whereas vascular protein clearance was
      reduced. The latter effect could almost entirely be explained by a decrease in
      intestinal capillary hydrostatic pressure. Therefore, in some experiments venous
      pressure was elevated and the microvascular reflection coefficient for total
      proteins was estimated at filtration-independent rates. This direct measurement
      of microvascular permeability was unaffected by exogenous nitric oxide. CAS 754
      did not increase permeability across monolayers of endothelial or epithelial
      cells and did not cause cell injury. Next, we assessed the possibility that
      excess nitric oxide may be detrimental, but only in inflamed intestine, by
      infusing CAS 754 with platelet-activating factor; the latter directly increases
      microvascular and mucosal permeability. CAS 754 did not exacerbate but rather
      reduced platelet-activating factor-induced rise in microvascular and mucosal
      permeability. These results suggest that high concentrations of nitric oxide do
      not cause breakdown of mucosal or microvascular barrier integrity under normal or
      inflammatory conditions.

PMID- 7631800
TI  - Enzyme- and mineralocorticoid receptor-controlled electrogenic Na+ absorption in
      human rectum in vitro.
AB  - In vivo electrogenic Na+ absorption (JeNa) in the human rectum is controlled by
      acute variation of aldosterone in nanomolar concentration range. In this study we
      report both the induction of JeNa in human rectum epithelium by nanomolar
      aldosterone added in vitro and the enzymatic control of glucocorticoid action on
      JeNa. JeNa was measured as amiloride-sensitive short-circuit current 8 h after
      addition of the respective steroid. Aldosterone (10 nM) caused JeNa of 5.7 +/-
      1.4 mumol.h-1.cm-2. Cortisol in the same concentration did not induce significant
      JeNa. Because cortisol is readily inactivated by 11 beta-hydroxysteroid
      dehydrogenase (11 beta-HSD), the true mineralocorticoid activity of cortisol was
      evaluated after inhibition of 11 beta-HSD by carbenoxolone. Carbenoxolone alone
      did not exhibit mineralocorticoid activity. If cortisol (10 nM) was given
      together with carbenoxolone (1 microM), the resulting JeNa (4.5 +/- 0.4 mumol.h
      1.cm-2) was not significantly different from that after 10 nM aldosterone,
      indicating equal intrinsic mineralocorticoid activity of cortisol and
      aldosterone. The same mechanisms were found in rat late distal colon. Kinetic
      data of carbenoxolone at 10 nM cortisol resulted in a Michaelis constant of 0.3
      microMs, maximal absorption of 8.4 mumol.h-1.cm-2, and a Hill coefficient of 1.8.
      The effects of carbenoxolone and glycyrrhetinic acid did not differ. We conclude
      that JeNa is under complete control of mineralocorticoid action. "Spontaneous"
      JeNa in the beginning of the in vitro period can be explained by elevated steroid
      levels before tissue removal.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7631801
TI  - Preservation of peristaltic reflex in hypertrophied ileum of guinea pig.
AB  - Chronic obstruction of the guinea pig ileum leads to distension and muscular
      hypertrophy, but how this affects passive biomechanical and nerve-mediated
      contractions and clearance known as peristaltic reflex is unclear. Ileum of
      controls had a diameter of 3.0 +/- 1.1 mm and a circular muscle thickness of 37.2
      +/- 11.2 microns; 4 wk after placement of a nonconstricting Gore-Tex band, the
      ileum was distended to 10.0 +/- 0.19 mm, and its muscle had hypertrophied to
      195.0 +/- 61.2 microns. Hypertrophied segments exceeded controls in capacity
      (e.g., 5.1 +/- 1.1 vs. 1.1 +/0 0.2 ml at 6 cm), compliance, and hysteresis.
      Threshold volumes and pressures that triggered the reflex were 3.3 +/- 1.3 ml and
      3.1 +/- 0.01 mmHg in hypertrophied vs. 0.7 +/- 0.2 ml and 1.5 +/- 0.2 mmHg in
      controls. The diameter increase that triggered the reflex was 1.4 +/- 0.1 mm in
      hypertrophied segments and 0.6 +/- 0.1 mm in controls. Hypertrophied segments
      generated fewer contractions of virtually double the amplitude and failed to
      generate a pressure differential between up- and downstream sites as controls
      did. Hypertrophied segments generated larger stroke volumes and cumulative
      clearance than controls. The ratio of antegrade to retrograde clearance was
      similar in hypertrophied and control segments. The length of the occluding
      segment in hypertrophied preparations exceeded that of controls. Control
      contractions indented the antimesenteric border and propagated antegrade from
      their site of origin; bizarre writhing movements of hypertrophied segments made
      their contractions difficult to monitor. Thus distension and muscular hypertrophy
      do not interfere with the ability of the chronically obstructed guinea pig ileum
      to generate a peristaltic reflex at least as readily and as powerful and as
      effective in clearing the lumen as controls.

PMID- 7631802
TI  - Location and regulation of low-density lipoprotein receptors in intestinal
      epithelium.
AB  - The expression, distribution, and some aspects of the regulation of low-density
      lipoprotein (LDL) receptors in rat intestinal epithelial cells were examined.
      Cells prepared by a perfusion technique provided a pure preparation of epithelial
      cells and could be manipulated to produce crypt-villus units or villi alone. On a
      total protein basis, the abundance of LDL receptors in villus cell membranes was
      half that in hepatic membranes. The level of receptors in both tissues was
      reduced by feeding an atherogenic diet but was increased only in the liver by
      ethinyl estradiol-induced hypocholesterolemia. The level of LDL receptor mRNA in
      intestinal epithelial cells was somewhat lower than in liver. Regulation of LDL
      receptor mRNA was similar to that of protein. Judged by the ratio of mRNA in
      villus cells to the villus-crypt unit and nuclear run-on assay for LDL receptor
      gene transcription, we conclude that LDL receptor mRNA is produced in the villus
      cells. The effect of fat feeding was regulated at the level of transcription.
      Expression in villus cells in ileum was severalfold higher than in jejunum and
      higher than in the liver. Together the results suggest serum cholesterol level is
      not the prime determinant of LDL receptor level in intestine, but LDL degradation
      in this organ may be regulated by factors in the lumen.

PMID- 7631803
TI  - Microscope laser light-scattering spectroscopy of vesicles within canaliculi of
      rat hepatocyte couplets.
AB  - Employing microscope laser light-scattering spectroscopy, we investigated
      "primary" bile secretion into canalicular spaces of rat hepatocyte couplets in
      monolayer culture. Time-dependent scattered light intensities were fitted by bi
      exponential decays. The "slow" decay was attributed to an undulating canalicular
      membrane motion, whereas the "fast" decay was consistent with rapidly diffusing
      intracanalicular vesicles with mean hydrodynamic radii (+/- SD) of 479 +/- 53 A.
      After addition of micromolar concentrations of common bile salts, increases in
      the amplitude of the fast component facilitated a quantitative estimate of
      vesicle secretion rates. A dose-response relationship with 0.1-200 microM sodium
      taurocholate was characterized by an initial concentration-dependent increase and
      then a decrease in the amplitude of the fast canalicular component. Since these
      taurocholate concentrations are nontoxic to cultured hepatocytes, the maximum in
      vesicle-sized particles at 10 microM taurocholate suggested that its critical
      micellar concentration of approximately 5 mM was attained within the canalicular
      spaces. Sodium taurolithocholate resulted in time- and dose-dependent diminution
      in vesicle secretion rates, which after 2 h was followed by spontaneous
      canalicular recovery. This suggested that acute bicellular "cholestasis" was
      followed by oxidative metabolism and detoxification of the monohydroxy bile salt.
      Microscope laser light-scattering spectroscopy should facilitate further physical
      chemical and pathophysiological studies of bile secretion at the cellular level.

PMID- 7631804
TI  - Agonist-mediated activation of PLA2 initiates Ca2+ mobilization in intestinal
      longitudinal smooth muscle.
AB  - Recent studies have shown that Ca2+ mobilization in longitudinal muscle is
      initiated by inositol 1,4,5-trisphosphate (IP3)-independent Ca2+ influx that acts
      as a trigger for Ca(2+)-induced Ca2R release. The present study examined whether
      arachidonic acid (AA) acts as mediator of the initial Ca2+ influx.
      Cholecystokinin octapeptide caused transient concentration-dependent increase in
      AA release in dispersed intestinal longitudinal but not circular muscle cells
      followed by sustained increase in both muscle cell types. The initial increase in
      AA release coincided with the initial Ca2+ transient and muscle contraction: all
      three events were abolished by guanosine 5'-O-(2-thiodiphosphate), pertussis
      toxin (PTX), and the phospholipase A2 (PLA2) inhibitor, dimethyleicosadienoic
      acid, but were not affected by calphostin C or neomycin. Exogenous AA caused
      concentration-dependent contraction and increase in cytosolic free Ca2+ ([Ca2+]i)
      in longitudinal but not circular muscle cells; both events were abolished by Ca2+
      channel blockers. Depletion of Ca2+ stores with thapsigargin attenuated with
      thapsigargin attenuated agonist- and AA-mediated increase in [Ca2+]i and
      contraction in longitudinal muscle cells: the residual [Ca2+]i increase (35%) and
      contraction (25%) reflected the component of Ca2+ influx. We conclude that AA
      released by agonist-mediated G protein-dependent PTX-sensitive activation of PLA2
      mediates Ca2+ influx, which then triggers Ca(2+)-induced Ca2+ release. The
      process is independent of phosphatidylinositol hydrolysis and occurs exclusively
      in longitudinal smooth muscle, in which Ca2+ release channels are highly
      sensitive to Ca2+, ryanodine, and cyclic ADP-ribose and insensitive to IP3.

PMID- 7631805
TI  - Bronchoalveolar lavage fluid phospholipase A2 activities are increased in human
      adult respiratory distress syndrome.
AB  - The role of phospholipase A2 (PLA2) in lung injury in humans is unclear. Previous
      studies have failed to identify an increase in PLA2 activity in bronchoalveolar
      lavage fluids (BALF) of patients with the adult respiratory distress syndrome
      (ARDS). In this study, increased phospholipase A2 (PLA2) activity was detected in
      BALF from patients with ARDS. PLA2 levels in BALF correlated positively with lung
      injury score in patients with lung disease. BALF PLA2 activity in patients with
      ARDS was resolved into heparin binding and nonbinding activities. Both PLA2
      activities were increased in BALF of ARDS patients. The PLA2 activity that bound
      to heparin was identified as a group II PLA2 by its chromatographic
      characteristics, its inhibition by dithiothreitol, its substrate specificity, and
      its approximate molecular mass of 14 kDa. The second PLA2 activity was further
      purified and found to require Ca2+ at a concentration > 2 x 10(-4) M for
      activity. This form of PLA2 exhibited a neutral and broad pH optimum (pH 6.0-8.0)
      and hydrolyzed both phosphatidylethanolamine and phosphatidylcholine effectively.
      Its apparent molecular mass was estimated to be 80-90 kDa. Neither anti
      pancreatic PLA2 antiserum nor anti-pig spleen cytosolic 100-kDa PLA2 antiserum
      immunoprecipitated the enzymatic activity. Thus at least two forms of PLA2 are
      increased in activity in BALF of patients with ARDS, a group II PLA2 and a
      biochemically and immunochemically form distinct from group I, group II, and
      cytosolic PLA2. Increased lung PLA2 activity may be important for the
      pathophysiology of ARDS.

PMID- 7631806
TI  - Pathways for uptake of fluorescently labeled liposomes by alveolar type II cells
      in culture.
AB  - Isolated alveolar type II cells are shown in real time to internalize 1-palmitoyl
      2-[12-[(7 nitro-2-1,3-benzoxadiazol-4-yl)amino]dodecanoyl] phosphatidyl choline
      (C12-NBD-PC)-labeled liposomes in an intact manner with the use of fluorescence
      microscopy. Cells isolated from rat lungs, cultured on plastic for 24 h, are
      exposed at 37 degrees C to liposomes on the microscope stage, using a
      microperfusion system. Liposomes composed of a self-quenching concentration of
      fluorophore (25 mol% C12-NBD-PC) do not dequench at the level of the plasma
      membrane; rather, they appear to fuse with intracellular lipids primarily in
      vesicular structures consistent with lamellar bodies. Temperature and energy
      dependence of this uptake mechanism is demonstrated by the lack of uptake of
      maximally fluorescent liposomes (15 mol% C12-NBD-PC) at 4 degrees C or when
      depleted of ATP. Inhibition of the coated-pit endocytic pathway by hypertonic
      media reduces fluorescent lipid uptake by 50%, suggesting a separate, clathrin
      independent endocytic pathway for intact internalization of liposomes by type II
      cells. Uptake is inhibited by cytochalasin D by 49%, suggesting a dependence on
      action, and by 88% with combined cytochalasin D and hypertonicity, or nearly the
      same level as ATP depletion. The evidence is consistent with the existence of two
      separate endocytic pathways for lipids in type II cells: one clathrin dependent
      and the other actin dependent.

PMID- 7631807
TI  - Migration and proliferation of guinea pig and human airway epithelial cells in
      response to tachykinins.
AB  - Restoration of the epithelial lining of a damaged airway is a necessary component
      of airway repair. Tachykinins, including substance P (SP) and neurokinin A (NKA),
      are localized to sensory nerves within the airway mucosa. These tachykinins
      regulate several airway functions, but their role in the repair of the epithelium
      has not been explored. To determine whether tachykinins stimulate migration and
      proliferation of airway epithelial cells, guinea pig tracheal epithelial (GPTE)
      and human bronchial epithelial (HBE) cells were grown in primary culture for 4-5
      days. Epithelial cell migration was assessed in a blindwell chemotaxis chamber,
      and proliferation was determined by immunohistochemistry after incorporation of
      the thymidine analogue 5-bromo-2'-deoxyuridine (BrdU). Both GPTE and HBE cells
      migrated after stimulation with 10(-11) M NKA [23.0 +/- 3.6 vs. 5.4 +/- 1.2 cells
      per 10 high-power fields (hpf), P < 0.001, n = 8 for GPTE cells; 18.4 +/- 2.3 vs.
      3.8 +/- 0.5 cells per 10 hpf for control, P < 0.001, n = 4 for HBE cells].
      Migration was stimulated within 2 h, was maximal after 6 h, and was attenuated
      substantially by the neurokinin 2 (NKA)-receptor antagonist SR-48968. NKA
      stimulated migration was both chemokinetic and chemotactic, and it could be
      blocked by inhibition of protein synthesis with cyclohexamide, inhibition of
      microtubular function with colchicine, or inhibition of actin microfilament
      elongation with cytochalasin D.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7631808
TI  - Disparate cytokine regulation of ICAM-1 in rat alveolar epithelial cells and
      pulmonary endothelial cells in vitro.
AB  - Intercellular adhesion molecule-1 (ICAM-1) is expressed at high levels on type I
      alveolar epithelial cells in the normal lung and is induced in vitro as type II
      cells spread in primary culture. In contrast, in most nonhematopoetic cells ICAM
      1 expression is induced in response to inflammatory cytokines. We have formed the
      hypothesis that the signals that control ICAM-1 expression in alveolar epithelial
      cells are fundamentally different from those controlling expression in most other
      cells. To test this hypothesis, we have investigated the influence of
      inflammatory cytokines on ICAM-1 expression in isolated type II cells that have
      spread in culture and compared this response to that of rat pulmonary artery
      endothelial cells (RPAEC). ICAM-1 protein, determined both by a cell-based enzyme
      linked immunosorbent assay and by Western blot analysis, and mRNA were minimally
      expressed in unstimulated RPAEC but were significantly induced in a time- and
      dose-dependent manner by treatment with tumor necrosis factor-alpha, interleukin
      1 beta, or interferon-gamma. In contrast, these cytokines did not influence the
      constitutive high level ICAM-1 protein expression in alveolar epithelial cells
      and only minimally affected steady-state mRNA levels. ICAM-1 mRNA half-life,
      measured in the presence of actinomycin D, was relatively long at 7 h in alveolar
      epithelial cells and 4 h in RPAEC. The striking lack of response of ICAM-1
      expression by alveolar epithelial cells to inflammatory cytokines is in contrast
      to virtually all other epithelial cells studied to date and supports the
      hypothesis that ICAM-1 expression by these cells is a function of cellular
      differentiation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7631809
TI  - Inhaled nitric oxide prevents neutrophil-mediated, oxygen radical-dependent leak
      in isolated rat lungs.
AB  - We found that ventilation with nitric oxide (NO, 50 ppm) significantly (P < 0.05)
      reduced capillary leak (as reflected by weight gain and Ficoll retention) in
      isolated rat lungs perfused for 60 min with N-formyl-methionyl-leucyl
      phenylalanine (fMLP; 10(-7) M) and human neutrophils (1,300/microliters).
      Perfusion with previously heated neutrophils (48 degrees C for 10 min, which
      inactivates NADPH oxidase) did not cause weight gain or Ficoll retention,
      indicating that neutrophil-derived oxidants mediated lung leak. Although
      perfusion with fMLP and neutrophils increased mean pulmonary artery pressures
      (PAP) from 7 to 11.7 +/- 0.5 mmHg at 10 min, lungs perfused with fMLP and
      neutrophils in which PAP was maintained at 7 mmHg by reducing perfusion flow
      rates also developed significant (P < 0.05) weight gain and Ficoll retention.
      Furthermore, inhaled NO did not reduce (P > 0.05) PAP at 10 min and only modestly
      reduced PAP at 30 and 60 min of perfusion. Our results suggest that oxidative
      endothelial damage, and not increased hydrostatic pressure, was the primary cause
      of the capillary leak, and that the protection provided by inhaled NO was not
      solely a consequence of vasodilation. We conclude that inhaled NO prevents
      neutrophil-mediated, oxygen radical-dependent leak in isolated rat lungs, and
      speculate that inhaled NO has anti-inflammatory properties in addition to its
      ability to cause pulmonary vasodilation.

PMID- 7631810
TI  - Kinetic analysis of cytosolic pH regulation in alveolar macrophages: V-ATPase
      mediated responses to a weak acid.
AB  - Three different mechanisms interact to control the cytosolic pH (pHi) of alveolar
      macrophages (M phi), namely, plasmalemmal vacuolar-type H(+)-ATPase (V-ATPase),
      Na+/H+ exchange, and Na(+)-independent HCO3-/Cl- exchange. To investigate the
      activity of plasmalemmal V-ATPase in alveolar M phi, we developed a nonlinear
      mathematical model of pHi regulation that incorporates the biophysical
      determinants of pHi and the fluxes of individual acid-base equivalents. The model
      was used to analyze the acid-base responses of rabbit alveolar M phi to a weak
      acid (propionic acid) under conditions that favored V-ATPase-mediated effects
      (presence of 1 mM amiloride and nominal absence of CO2). The pHi was measured
      using the fluorescent probe, 2',7'-biscarboxethyl-5,6-carboxyfluorescein. M phi
      exposure to propionic acid caused a rapid fall in pHi. Recovery of pHi after acid
      loading varied directly with the magnitude of the acid load. Mathematical
      analyses showed that pHi recovery was hindered by persistent influx of propionic
      acid driven, in turn, by transporter-mediated H+ extrusion and propionate efflux.
      Eventually, a new steady state was established in which propionate and H+ were
      cycled out of the M phi and propionic acid was recycled into the cell. As a
      consequence, model predictions of the rate of V-ATPase-mediated H+ efflux were
      almost twice that estimated from experimental determinations of the initial rate
      of pHi recovery.

PMID- 7631812
TI  - Bradykinin stimulates bronchial epithelial cells to release neutrophil and
      monocyte chemotactic activity.
AB  - In the present investigation, we evaluated the potential of bradykinin (BK),
      histamine, and serotonin to induce the release of neutrophil and monocyte
      chemotactic activity (NCA and MCA) from bronchial epithelial cells (BEC). BK
      significantly stimulated BEC to release NCA and MCA in a dose- and time-dependent
      manner. Histamine weakly but significantly induced the release of both NCA and
      MCA in a similar fashion. Serotonin did not stimulate BEC. Checkerboard analysis
      showed that the NCA and MCA released in response to BK were chemotactic.
      Molecular-sieve column chromatography by Sephadex G-75 revealed that BK induced a
      single low-molecular-weight peak (approximately 400 Da) for both NCA and MCA. The
      releases of NCA and MCA in response to BK and histamine were inhibited by
      lipoxygenase inhibitors (P < 0.01). The released NCA was inhibited by leukotriene
      B4 (LTB4) receptor antagonist (P < 0.01) and was slightly inhibited by platelet
      activating factor receptor antagonist. LTB4 was increased in BK-stimulated BEC
      supernatant (P < 0.01). BK B2-receptor antagonist attenuated the release of NCA
      and MCA. These data suggest that BK and histamine may stimulate BEC to release
      NCA and MCA and may modulate neutrophil and monocyte recruitment into the airways
      in patients with asthma.

PMID- 7631811
TI  - Purinergic regulation of ion transport across nonciliated bronchiolar epithelial
      (Clara) cells.
AB  - Previous studies demonstrated that elevation of intracellular calcium
      concentration ([Ca2+]i) increased electrogenic anion transport by bronchiolar
      epithelia. Extracellular nucleotides were shown to elevate [Ca2+]i and
      transepithelial short-circuit current (Isc) in proximal airways epithelia. In
      this study purine and pyrimidine nucleotides were investigated for their ability
      to regulate ion transport by rabbit nonciliated bronchiolar epithelial (Clara)
      cells in culture. ATP in the apical bath induced a concentration-dependent
      transient increase in [Ca2+]i and Isc. Mean effective doses (ED50) of the
      responses were 10(-7) M and 10(-6) M, respectively. Transepithelial resistance
      (Rt) decreased. The peak changes in Isc and Rt were 7.8 +/- 1.2 microA/cm2 and 
      59 +/- 14 omega.cm2 (n = 26, basal Isc = 47.4 +/- 4.3 microA/cm2 and Rt = 428 +/-
      40 omega.cm2). Some preparations exhibited a small residual increase in Isc after
      the initial response, but the change was not statistically significant (delta Isc
      = 1.7 +/- 1.2 microA/cm2, n = 18). Addition of ATP to the basolateral bath had no
      detectable effects. Purinoceptor agonists were used to characterize the receptors
      mediating the change in Isc. UTP and ATP gamma S increased Isc and inhibited
      subsequent stimulation by ATP. ADP, ADP beta S, 2-methylthio-ATP, and alpha, beta
      methylene-ATP had negligible effects on the peak delta Isc and subsequent
      stimulation by ATP. The ionic mechanism underlying the ATP-induced increase in
      Isc was investigated with the use of specific ion-transport inhibitors and by ion
      substitution.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7631813
TI  - Optimization of cationic lipid-mediated gene transfer to airway epithelia.
AB  - The use of cationic lipids for gene transfer to airway epithelia has shown
      promise in in vitro and in vivo studies. However, previous studies have used a
      wide variety of different lipid preparations and different formulations. Few
      studies have been designed to optimize the variables involved in transfection,
      and none have been focused on airway epithelia. Therefore we examined variables
      that affect cationic lipid-mediated transfection of HeLa cells and of airway
      epithelial cells grown on permeable filter supports at the air-liquid interface.
      To quantitate expression of cDNA, we assayed expression of luciferase. We found
      that the ratio of DNA to lipid was an important variable that determined
      transfection efficiency. In both HeLa and airway epithelial cells, the optimum
      charge ratio of cationic lipid to anionic DNA was approximately 1.25, consistent
      with the notion that a positively charged complex facilitates interaction with
      the negatively charged cell membrane. After testing a series of readily available
      cationic lipids, we found that 1,2-dimyristyloxypropyl-N,N-dimethyl-hydroxyethyl
      ammonium bromide (DMRIE)/dioleoyl phosphatidylethandamine (DOPE) appeared to show
      good efficacy. The concentration of DNA and cationic lipid also played an
      important role: in HeLa cells the optimum concentration of cationic lipid was
      approximately 5 microM and in airway epithelial cells was approximately 15
      microM.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7631814
TI  - Hypoxia and reoxygenation stimulate biphasic changes in endothelial monolayer
      permeability.
AB  - Incubation of bovine pulmonary microvascular endothelial (BPMVE) cells in low O2
      content (95% N2-5% CO2) for 4 h increased monolayer permeability to dextran
      almost twofold and also increased the incidence of intercellular gaps and
      intracellular actin stress fibers. Hypoxic incubation decreased the extracellular
      matrix contents of fibronectin and vitronectin, proteins that serve as anchorage
      points for the endothelial cells. This state was reversed after 24 h of hypoxic
      incubation, and the BPMVE monolayer permeability to dextran was less than that of
      normoxic controls. The monolayer had fewer intercellular gaps and stress fibers,
      and the extracellular matrix contained increased amounts of fibronectin,
      vitronectin, and type I collagen. These alterations stimulated by 24 h of hypoxic
      incubation were resolved within 4 h of reoxygenation in room air supplemented
      with 5% CO2. These studies indicate that incubation of endothelial monolayers in
      hypoxic conditions first increases and then decreases monolayer permeability,
      through increased and decreased formation of intercellular gaps.

PMID- 7631815
TI  - Inhibition of poly(ADP-ribose) polymerase preserves surfactant synthesis after
      hydrogen peroxide exposure.
AB  - Exposure to hydrogen peroxide (H2O2) decreases phosphatidylcholine (PC) synthesis
      in rabbit type II pneumocytes. Activation of poly(ADP-ribose) polymerase (PARP)
      may play a role in this process. Exposure of type II pneumocytes to H2O2 resulted
      in a 53% decrease in the rate of incorporation of [3H]choline into PC (P <
      0.001). Cell NAD and ATP levels were decreased by 52% (P < 0.001) and 39% (P <
      0.01), respectively, without significant changes in cell viability. Exposure to
      H2O2 also resulted in a 52% (P < 0.05) increase in the activity of PARP.
      Preincubation of type II cells with inhibitors of PARP (nicotinamide; 3
      aminobenzamide) before H2O2 exposure prevented the increase in PARP activity, and
      blocked the decreases in ATP, NAD, and rate of PC synthesis. These results
      suggest that the energy depletion associated with activation of PARP contributes
      to the effects of oxidant stress on type II cell metabolic function and may be
      ameliorated by pharmacological agents in vitro.

PMID- 7631816
TI  - Genetic control of susceptibility to ozone-induced changes in mouse tracheal
      electrophysiology.
AB  - Genetic factors influence the responses of humans and rodents to ozone (O3)
      inhalation. We previously demonstrated differential O3-induced decreases of
      tracheal potential (VT) in C57BL/6J (B6) and C3H/HeJ (C3) strain mice. To
      characterize the genetic basis of this strain-specific response, we measured VT
      in progeny of B6 and C3 strain mice and in six additional inbred strains of mice
      6 h after O3 exposures (2 ppm x 3 h). First filial generation (F1) mice and
      second generation backcrosses with the resistant parent were uniformly resistant.
      The distribution of VT in second generation backcrosses with the susceptible
      parent resembled that of a population composed of resistant and susceptible mice
      in a 1:1 ratio. These data suggested simple autosomal recessive inheritance of
      susceptibility. However, overlapping distributions prevented statistical
      confirmation of that hypothesis. Strain screening revealed a susceptible
      phenotype in 129/J, A/J, B6, C3HeB/FeJ, and SJL/J and a resistant phenotype in
      AKR/J, C3, and CBA/J inbred mouse strains. Because this pattern of susceptibility
      to changes in VT differs from that of susceptibility to lung inflammation, the
      genetic factors that determine these two responses to acute O3 are not identical.

PMID- 7631817
TI  - Characterization of zinc uptake and its regulation by arachidonic acid in fetal
      type II pneumocytes.
AB  - In freshly isolated fetal guinea pig type II pneumocytes, zinc uptake is time and
      temperature dependent. Two pathways of uptake exist, resulting in a rapid phase
      that reaches a steady state within 30 s and a slower linear phase that does not
      attain a steady state within 60 min. Both processes exhibit saturation kinetics.
      The rapid phase has a maximal zinc uptake of 60.7 +/- 9.3 pmol.10(6) cells-1.30 s
      1 and an apparent affinity (Kt) of 13.7 +/- 5.4 microM. The maximum velocity of
      uptake (Vmax) of the slower phase is 24.6 +/- 1.9 pmol.10(6) cells-1.min-1 with a
      Kt of 22.0 +/- 3.6 microM. Epinephrine, terbutaline, dibutyryl adenosine 3',5'
      cyclic monophosphate, and dexamethasone have no significant effect on zinc
      uptake, while arachidonic acid (AA) stimulates. Dose-response data of AA
      stimulated zinc uptake gives an apparent K0.5 of 0.42 +/- 0.01 microM and a Hill
      coefficient of 1. The maximal uptake in the rapid phase is significantly
      increased to 146.8 +/- 12.4 pmol.10(6) cells-1.30 s-1 and in the slow phase, the
      Vmax for zinc uptake is also significantly increased to 33.0 +/- 1.8 pmol.10(6)
      cells-1.min-1 by 10 microM AA. However, the Kt values in both processes remain
      unchanged after AA stimulation. The effect is not mediated by either leukotrienes
      or prostaglandins but can be mimicked by other unsaturated fatty acids.

PMID- 7631818
TI  - Reduction of thiazine dyes by bovine pulmonary arterial endothelial cells in
      culture.
AB  - The uptake of methylene blue (MB), and toluidine blue O (TBO) by bovine pulmonary
      arterial endothelial cells grown on microcarrier beads was detected as a decrease
      in the concentration of dye in the medium after these thiazine dyes were added to
      the medium surrounding the cells. Because the reduced forms of these dyes are
      much more lipophilic than the oxidized forms, we considered the possibility that
      reduction of the dyes at the cell surface might have preceded the uptake by the
      cells. Therefore, we studied the ability of the cells to reduce a toluidine blue
      O-polyacrylamide polymer (TBOP), which was too large to enter the cells in either
      the oxidized or reduced form. The TBO moieties of the polymer were reduced by the
      cells, indicating that the dyes did not have to enter the cells to be reduced and
      that reduction can occur at, or near, the cell surface. The rate of TBOP
      reduction was about the same as the rate of uptake of the monomeric dyes,
      indicating that the cell surface reduction mechanism had a sufficient capacity to
      account for the monomer uptake by the cells. We also found that ferricyanide ion,
      which also did not permeate the cells, was reduced by the cells and that external
      ferricyanide inhibited the monomeric MB uptake. Thus the results with
      ferricyanide were also consistent with the concept that the monomeric thiazine
      dyes are reduced at the cell surface before the more lipophilic reduced forms are
      taken up by the endothelial cells.

PMID- 7631819
TI  - Airways of a hyperresponsive rat strain show decreased relaxant responses to
      sodium nitroprusside.
AB  - The aim of the current studies was to investigate the possibility that a
      decreased relaxant response to nitric oxide (NO) might contribute to strain
      related differences in airway responsiveness in the rat. Isolated tracheal rings
      from hyperresponsive. Fisher rats were confirmed to be more responsive to
      carbachol [mean effective concentration (EC50) = 2.45 x 10(-7) M] than those from
      Lewis (EC50 = 3.60 x 10(-7) M, P < 0.03) and ACI (EC50 = 3.85 x 10(-7) M, P <
      0.01) rats. Sodium nitroprusside (SNP), a NO donor, caused relaxation of the
      carbachol (10(-6) M) contracted tracheal rings, but the half-maximal inhibition
      concentration (IC50) SNP in Fisher rats (5.60 x 10(-6) M) was significantly
      higher than in Lewis (1.34 x 10(-6) M, P < 0.001) and ACI rats (1.13 x 10(-6) M,
      P < 0.0005). The inhibitory effect of SNP on airway responsiveness to inhaled
      methacholine (MCh) in vivo was also less pronounced for Fisher than Lewis rats.
      SNP induced an accumulation of guanosine 3',5'-cyclic monophosphate (cGMP) in
      cultured tracheal smooth muscle cells (TSM). Fisher TSM produced less cGMP on
      exposure to SNP compared with TSM from ACI (P < 0.01) and Lewis (P < 0.0001)
      rats. A decreased guanylyl cyclase activity may account for the impaired relaxant
      effect of SNP in Fisher rats.

PMID- 7631820
TI  - Regulation of interleukin-1 receptor antagonist by Th1 and Th2 cytokines.
AB  - Airway inflammation is an important aspect of asthma. Recent studies of airway
      inflammation in asthma have focused attention on cytokines released by T helper
      lymphocyte type 1 (Th1)- and Th2-like T cells. Interleukin (IL)-1 is also
      increased in the airways of asthmatics, and it is most likely derived from airway
      and alveolar macrophages. The effects of Th1 or Th2 cytokines on the release of
      IL-1 or its specific antagonist, IL-1ra, have not been well studied. We examined
      the response of THP-1 cells, a myelomonocytic cell line, to stimulation with
      various Th1 and Th2 cytokines and found that IL-4, IL-10, and IFN-gamma increased
      IL-1ra mRNA and protein release. The increase in mRNA was not due to an increase
      in IL-1ra mRNA stability. IL-4 (10 ng/ml) increased IL-1ra release from 9,641 +/-
      322 [from cells stimulated with lipopolysaccharide (LPS) alone] to 50,796 +/-
      1,917 pg/ml (from cells stimulated with LPS and IL-4). IL-10 (10 ng/ml) caused a
      similar upregulation of IL-1ra from LPS-stimulated cells: 87,478 +/- 7,808
      compared with 8,004 +/- 1,166 pg/ml released from the cells stimulated with LPS
      alone. Cells stimulated with IFN-gamma (100 U/ml) and LPS released 27,854 +/-
      3,626 pg/ml of IL-1ra, compared with 9,069 +/- 236 pg/ml in the presence of LPS
      alone. In addition, the Th1 cytokine, IFN-gamma, but not the Th2 cytokines, IL-4
      and IL-10, upregulated IL-1 beta mRNA and increased the release of IL-1 beta
      protein. Similar studies were performed using freshly isolated
      monocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7631821
TI  - Regulation of endothelial cell gap formation and barrier function by myosin
      associated phosphatase activities.
AB  - Thrombin-induced cultured bovine endothelial cell (EC) gap formation and albumin
      permeability is initiated by contraction, which is dependent upon myosin light
      chain kinase-mediated myosin light chain (MLC) phosphorylation. MLC are then
      rapidly dephosphorylated (J. G. N. Garcia, H. W. Davis, and C. E. Patterson, J.
      Cell. Physiol. 163: 510-522, 1995), suggesting a role for MLC dephosphorylation
      in regulation of EC barrier function. Therefore, we studied the effect of
      semiselective protein phosphatase (PPase) inhibitors, calyculin A and okadaic
      acid, on MLC phosphorylation status, myosin-associated PPase activity, and EC
      monolayer permeability. Calyculin A (0.1-10 nM), but not okadaic acid (1-100 nM)
      produced significant dose-dependent enhancement of both MLC phosphorylation
      (three- to four-fold) and EC permeability (eightfold). EC homogenates were
      utilized to assess Ser/Thr PPase activities using either [32P]phosphorylase A or
      32P-labeled skeletal MLC as substrates. Calyculin A at 5 nM (sufficient to
      inhibit type 1 and type 2A PPase) produced approximately 95% inhibition of all EC
      PPase activity against both substrates, whereas 2 nM okadaic acid (selective for
      PPase 2A) only partially inhibited EC PPase activity (40-60%). Fractionation of
      EC homogenates produced a supernatant fraction containing < 10% of total myosin
      and a pellet fraction with > 90% of total myosin. PPase activity in the myosin
      enriched pellet was insensitive to 2 nM okadaic acid (0% inhibition) but
      sensitive to 5 nM calyculin (> 95% inhibition). Immunoreactive PPase 1 was
      present in both fractions, whereas PPase 2A was present only in the myosin
      depleted fraction. We conclude that a type 1 myosin-associated PPase is involved
      in regulation of EC contractility and barrier function.

PMID- 7631822
TI  - Function and structure of H-K-ATPase in the kidney.
AB  - The present review summarizes recent functional and structural evidence
      indicating that the kidney possesses at least one and probably more than one
      isoform of a proton- and potassium-activated adenosinetriphosphatase (H-K
      ATPase). Functional studies have examined in detail the mechanism of luminal
      acidification and K/Rb absorption by the outer medullary collecting duct (OMCD)
      from the inner stripe, a high-capacity distal site of urinary acidification.
      These studies indicate that the mechanism of proton secretion in this segment is
      similar to a model proposed for gastric acid secretion. Specifically, the
      profound effect of H-K-ATPase inhibitors or luminal K removal on net bicarbonate
      (HCO3) absorption indicates a major role for an H-K pump in luminal acidification
      by the OMCD. The importance of an H-K-ATPase is further supported by the finding
      that nanomolar concentrations of bafilomycin A1, which specifically inhibit
      vacuolar-type H-ATPase, have significantly smaller effects on net HCO3 absorption
      than do H-K-ATPase inhibitors. Studies on the perfused inner medullary collecting
      duct (IMCD) and cultured IMCD cells also suggest a significant role for H-K
      ATPase in luminal acidification by the IMCD. Evidence has accrued from studies in
      the cortical CD and OMCD that the mechanism of H-K-ATPase-mediated luminal proton
      secretion differs under K-replete and K-restricted conditions. In K repletion,
      luminal K ions transported by the pump recycle back into the lumen by a Ba
      sensitive mechanism. However, in K restriction, the mechanism of the H-K-ATPase
      involves luminal proton secretion and K absorption that is insensitive to luminal
      Ba and, by inference, apical K recycling. Moreover, in K restriction, K/Rb
      absorption is inhibited by basolateral Ba, indicating that the pump operates to
      reabsorb K/Rb across the epithelium. The structural evidence reviewed here
      indicates the presence of mRNA within the mammalian kidney that is either
      identical or highly homologous to mRNAs for gastric and putative colonic H-K
      ATPase alpha-subunits and gastric H-K-ATPase beta-subunit. Localization of these
      transcripts by in situ hybridization demonstrates gastric alpha- and beta-subunit
      mRNAs in intercalated cells of both the cortical and medullary CD, principal
      cells of the CD, and IMCD cells. Additional studies in transgenic mice indicate
      that regulatory sequences upstream to the H-K-ATPase beta-subunit gene direct
      transcription in both gastric parietal cells and the renal CD.(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 7631823
TI  - Hypertonic NaCl enhances adenosine release and hormonal cAMP production in mouse
      thick ascending limb.
AB  - Adenosine 3',5'-cyclic monophosphate (cAMP), accumulated in the presence of
      adenosine, was measured in medullary portions of mouse thick ascending limbs of
      Henle's loop, suspended either in classic extracellular buffer or in the presence
      of added NaCl. Under control conditions (140 mmol/l NaCl), adenosine (< 10(-5)
      mol/l) and N6-cyclohexyladenosine, an A1 adenosine receptor agonist, inhibit the
      cAMP accumulation induced by arginine vasopressin (AVP). On the other hand, high
      concentrations of adenosine and CGS-21680, an A2 adenosine receptor agonist,
      stimulate cAMP formation. Addition of NaCl (+300 mmol/l) to extracellular buffer
      stimulates the release of endogenous adenosine. It also enhances A2 receptor
      induced cAMP accumulation but suppresses A1 receptor-mediated inhibition of
      adenylyl cyclase. This hypertonic NaCl medium also potentiates the stimulatory
      action of AVP on adenylyl cyclase. The modifications of tubular responses to both
      AVP and A1 and A2 agonists, brought about by hypertonic NaCl, were all inhibited
      by adenosine deaminase, thereby demonstrating the involvement of endogenous
      adenosine. Adenosine, the release and the effects of which are modulated by
      hypertonic NaCl, thus appears to act as an endogenous physiological modulator of
      kidney medulla function.

PMID- 7631824
TI  - Angiotensin II regulates nephrogenesis and renal vascular development.
AB  - To test the hypothesis that angiotensin II (ANG II) is necessary for normal
      embryonic and postnatal kidney development, the effect of angiotensin receptor
      blockade or angiotensin converting enzyme inhibition on nephrovascular
      development was studied in newborn Sprague-Dawley rats and in Rana catesbeiana
      tadpoles undergoing prometamorphosis. Blockade of ANG II type 1 receptor (AT1) in
      newborn rats induced an arrest in nephrovascular maturation and renal growth,
      resulting in altered kidney architecture, characterized by fewer, thicker, and
      shorter afferent arterioles, reduced glomerular size and number, and tubular
      dilatation. Inhibition of ANG II generation in tadpoles induced even more marked
      developmental renal abnormalities. Blockade of ANG II type 2 receptor (AT2) in
      newborn rats did not alter renal growth or morphology. Results indicate that ANG
      II regulates nephrovascular development, a role that is conserved across species.

PMID- 7631826
TI  - Endogenous ANP in postischemic acute renal allograft failure.
AB  - Circulating atrial natriuretic peptide (ANP) levels and glomerular binding sites
      for ANP were examined in 23 subjects undergoing renal transplantation. Subjects
      were divided into two groups, group 1 (n = 12) with prompt and group 2 (n = 11)
      with delayed allograft function. Sixty to 180 min after graft reperfusion,
      renovascular resistance was threefold higher and glomerular filtration rate (GFR)
      depressed by 79% in group 2 vs. group 1. Corresponding median plasma ANP (114 vs.
      140 pg/ml) and guanosine 3',5'-cyclic monophosphate (cGMP) levels (22 vs. 28
      pmol/ml) were similarly elevated in the two groups [P = not significant (NS)].
      Autoradiographic analysis of glomeruli in an allograft biopsy revealed the median
      density of total receptors (24 vs. 28 fmol/mm3), A receptors (15 vs. 19
      fmol/mm3), and C receptors (6 vs. 9 fmol/mm3) for ANP to also be similar in group
      2 vs. group 1, respectively (P = NS). By postoperative day 3, allograft GFR
      averaged only 6 +/- 2 in group 2 vs. 59 +/- 4 ml/min in group 1. Median plasma
      ANP levels doubled in each group to 262 and 251 pg/ml, respectively (P = NS).
      However, median values for plasma levels (38 vs. 17 pmol/ml) and the fractional
      clearance of cGMP (1.9 vs. 1.2) were significantly higher in group 2 than group
      1. We conclude that, despite an adequate density of glomerular ANP receptors and
      enhanced cGMP generation, neither renal vasoconstriction nor hypofiltration is
      alleviated by a progressive elevation of plasma ANP levels in renal transplant
      recipients with sustained postischemic injury. We infer that constricted afferent
      arterioles are unresponsive to the vasorelaxant action of endogenous ANP in this
      form of postischemic, acute renal failure.

PMID- 7631825
TI  - Luminal acidification in K-replete OMCDi: inhibition of bicarbonate absorption by
      K removal and luminal Ba.
AB  - We have previously demonstrated that significant luminal acidification in the K
      replete rabbit inner stripe of the outer medullary collecting duct (OMCDi) occurs
      via a renal H-K-adenosinetriphosphatase (H-K-ATPase) sensitive to several of the
      gastric H-K-ATPase inhibitors. To investigate further the mechanism of K
      dependent luminal acidification in K-replete OMCDi, we examined the effects of
      luminal K removal, luminal addition of Ba in the presence and absence of luminal
      5.0 nM bafilomycin A1 (BAF), and basolateral addition of Ba on net bicarbonate
      flux (JtCO2, pmol.mm-1.min-1) and transepithelial voltage (VT, mV). Removal of K
      from the perfusate inhibited JtCO2 by 74% (13.4 +/- 4.0 for control, 3.5 +/- 1.4
      pmol.mm-1.min-1 for experimental, P < 0.05) and was statistically equivalent to
      the degree of inhibition previously observed under identical experimental
      conditions by either 10 microM Sch-28080 or 10 microM A-80915A. Approximately 50%
      inhibition of JtCO2 was observed following luminal application of 2.0 mM Ba2+,
      and the degree of inhibition was statistically equivalent regardless of whether
      BAF was present (12.2 +/- 2.7 for control, 6.0 +/- 1.4 pmol.mm-1.min-1 for 2.0 mM
      Ba2+, P < 0.05; 9.6 +/- 1.2 for control with 5 nM BAF, 5.7 +/- 1.3 pmol.mm-1.min
      1 for 2.0 mM Ba2+ with 5 nM BAF, P < 0.05). Additionally, increasing the luminal
      concentration of Ba2+ from 2.0 to 4.0 mM resulted in no further inhibition of
      JtCO2 (8.5 +/- 1.7 for control, 3.9 +/- 1.3 pmol.mm-1.min-1 for 4.0 mM Ba2+, P =
      0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7631827
TI  - Role of renal nerves in natriuresis of L-NMMA infusion in SHR and WKY rats.
AB  - The purpose of this study was to determine the role of the renal nerves in the
      natriuresis and diuresis that is observed with the systemic infusion of a high
      dose of NG-monomethyl-L-arginine (L-NMMA) to inhibit nitric oxide synthesis in
      the Okamoto spontaneously hypertensive rat (SHR) and the Wistar-Kyoto (WKY) rat.
      All rats in this study underwent a unilateral nephrectomy approximately 2 wk
      prior to the acute experiment. On the day of the acute experiment, renal
      denervation of the remaining left kidney was performed in one group of SHR (n =
      6) and one group of WKY rats (n = 9). Another group of SHR (n = 6) and WKY rats
      (n = 10) had an innervated kidney. A control clearance period was taken, and then
      an L-NMMA (15 mg/kg bolus followed by 500 micrograms.kg-1.min-1 continuous
      infusion) infusion period followed in all four groups of rats. In the innervated
      SHR and WKY rats, the increases in fractional excretion of sodium (FENa) were
      5.11 +/- 0.70 and 3.58 +/- 0.38%, respectively, with the infusion of L-NMMA and
      were associated with significant increases in fractional excretions of phosphate
      (FEPi; 18.18 +/- 5.33 and 6.34 +/- 2.29%, respectively), suggesting a reduction
      in proximal tubule reabsorption. In the SHRs with acute renal denervation, FENa
      was significantly increased by L-NMMA; however, FENa was significantly reduced
      (2.03 +/- 0.70%; P < 0.05) in comparison with innervated SHRs and was associated
      with no increase in FEPi (FEPi = -0.72 +/- 1.23%).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7631828
TI  - Polarity and transport properties of rabbit kidney proximal tubule cells on
      collagen IV-coated porous membranes.
AB  - A high degree of functional polarity has been obtained in primary cultures of
      rabbit kidney proximal tubule cells grown on collagen IV-coated porous membranes.
      Tight confluency was attained 6 days after seeding and maintained for at least 6
      more days, as shown by analysis of paracellular inulin diffusion. From day 6
      onward, L-lactate, ammonia, and D-glucose concentration gradient and a pH
      difference of approximately 1 unit developed between the two nutrient medium
      compartments. Confluent monolayers expressed organic ion transport properties
      higher than those formerly reported for other cell models. Transcellular
      transport of 20 microM tetraethylammonium was directed from basal to apical
      compartment and was specifically inhibited by mepiperphenidol (1 mM).
      Unidirectional transport of 2.4 microM p-aminohippurate also occurred from basal
      to apical compartment, was saturable, and specifically inhibited by probenecid (1
      mM). These results suggest that rabbit kidney proximal tubule cells, cultured
      under the experimental conditions described here, may be a useful model for the
      in vitro study of highly polarized renal transport processes.

PMID- 7631829
TI  - Differential interaction of human renal P-glycoprotein with various metabolites
      and analogues of cyclosporin A.
AB  - Interactions of P-glycoprotein with several analogues and metabolites of
      cyclosporin A were studied to gain a better understanding of this
      immunosuppressant's mechanism of excretion and nephrotoxicity. Incorporation of
      [3H]azidopine into human renal P-glycoprotein in the presence of various
      concentrations of different cyclosporins was quantitated. Competitive
      [3H]azidopine photolabeling and 3H drug transport assays of CHRC5 multidrug
      resistant cells were also conducted to evaluate effects of cyclosporins on P
      glycoprotein function. Cyclosporins A [half-maximal inhibition constant (K0.5) =
      20 nM] and G (K0.5 = 40 nM) blocked [3H]azidopine photolabeling of renal P
      glycoprotein at very low concentrations, whereas higher concentrations of
      cyclosporin C (K0.5 = 500 nM) and metabolites 1, 17, and 21 (K0.5 = 200 nM) were
      required to inhibit photolabeling. Metabolites H and 8 were ineffective in
      inhibition of [3H]azidopine photolabeling of human renal P-glycoprotein.
      Similarly, cyclosporins A, C, and G were the best inhibitors of [3H]azidopine
      photolabeling of P-glycoprotein in multidrug-resistant C5 cells; the various
      metabolites were less effective. Cyclosporins A, C, and G also enhanced cellular
      accumulation of [3H]cyclosporin A and several other 3H-labeled compounds known to
      be transported by P-glycoprotein in multidrug-resistant C5 cells. Differential
      affinities of cyclosporin A metabolites for P-glycoprotein suggest considerable
      drug-binding site specificity. Our current hypothesis is that cyclosporin A may
      be more nephrotoxic than its metabolites by virtue of its superior ability to
      bind to and competitively inhibit urinary excretion of an endogenous P
      glycoprotein substrate. Our findings provide the basis for future design and
      testing of new cyclosporin derivatives that have immunosuppressive activity yet
      may be less nephrotoxic because of their poor interaction with renal P
      glycoprotein.

PMID- 7631830
TI  - Comparison of systemic and direct intrarenal angiotensin II blockade on sodium
      excretion in rats.
AB  - To dissociate the renal effects from the systemic effects of angiotensin II
      blockade, the present study was designed to determine the effects of systemic and
      renal interstitial infusion of the specific angiotensin II (ANG II) receptor
      antagonist, losartan, on blood pressure and sodium excretion in rats fed a low-,
      normal, or high-sodium diet. Fractional sodium excretion (FENa) and mean arterial
      pressure (MAP) were measured in rats before and during systemic infusion of
      losartan (10 mg/kg) or renal interstitial infusion of losartan (3 mg/kg) by means
      of a chronically implanted matrix. In rats fed a low- or normal sodium diet,
      systemic infusion of losartan markedly decreased MAP (delta -21 +/- 2, delta -10
      +/- 2 mmHg, respectively; P < 0.05) with an accompanying fall in FENa (delta 
      0.10 +/- 0.05, delta -0.91 +/- 0.40%, respectively; P < 0.05). In contrast,
      preferential blockade of renal ANG II with renal interstitial losartan infusion
      resulted in an increase in FENa (delta 0.13 +/- 0.04, delta 0.95 +/- 0.45%,
      respectively; P < 0.05) and no significant change in MAP. In rats fed a high
      sodium diet, both systemic and renal interstitial infusion of losartan increased
      FENa (delta 1.90 +/- 0.26, delta 1.40 +/- 0.56%, respectively; P < 0.05).
      Although systemic infusion of losartan decreased MAP (delta -4.4 +/- 0.6 mmHg, P
      < 0.05) in rats fed a high-sodium diet, the reduction in MAP was much less than
      that in rats fed a low- and normal sodium diet.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7631831
TI  - Prostaglandin E2 regulation of ion transport is absent in medullary thick
      ascending limbs from SHR.
AB  - Regulation of HCO3- and Cl- absorption by arginine vasopressin (AVP) and
      prostaglandin E2 (PGE2) was examined in isolated, perfused medullary thick
      ascending limbs (MTAL) from 4- to 7-wk-old spontaneously hypertensive (SHR) and
      Wistar-Kyoto (WKY) rats. AVP inhibited HCO3- absorption by 50% at 10(-10) M and
      by 25% at 2 x 10(-12) M in MTAL from both WKY and SHR. Cholera toxin (10(-9) M)
      or forskolin (10(-6) M) in the bath also inhibited HCO3- absorption by 50% in the
      SHR. In MTAL from WKY, PGE2 (10(-6) M in the bath) increased HCO3- absorption
      from 7.1 +/- 0.4 to 12.0 +/- 0.4 pmol.min-1.mm-1 (P < 0.005) and decreased Cl-
      absorption from 65 +/- 7 to 47 +/- 6 pmol.min-1.mm-1 (P < 0.001) in the presence
      of 10(-10) M AVP. Under the same conditions, PGE2 had no effect on HCO3- or Cl-
      absorption in MTAL from SHR. PGE2 also reversed submaximal inhibition of HCO3-
      absorption by 2 x 10(-12) M AVP in WKY but not in SHR. With 10(-10) M AVP in the
      bath, phorbol 12-myristate 13-acetate (10(-6) M in the bath) increased HCO3-
      absorption from 6.6 +/- 0.5 to 12.3 +/- 0.4 pmol.min-1.mm-1 in MTAL from WKY and
      from 7.6 +/- 0.7 to 12.6 +/- 1.2 pmol.min-1.mm-1 in MTAL from SHR (P < 0.005).
      These results demonstrate that 1) the effects of PGE2 to stimulate HCO3-
      absorption and inhibit Cl- absorption in the presence of AVP are absent in MTAL
      from SHR, 2) the defect may involve an inability of PGE2 to stimulate protein
      kinase C, and 3) regulation of HCO3- absorption by AVP via adenosine 3',5'-cyclic
      monophosphate is similar in MTAL from WKY and SHR. The lack of PGE2 inhibition of
      NaCl absorption in the MTAL may contribute to renal salt retention during the
      development of hypertension in the SHR.

PMID- 7631832
TI  - Diffusive transport of solute in the rat medullary microcirculation.
AB  - Outer medullary descending vasa recta (OMDVR) permeability to sodium (PNa) is
      much lower than to urea (Purea). Based on these findings, we hypothesized that
      sodium and urea diffuse across the OMDFR wall by separate routes. To further test
      this, we simultaneously perfused OMDVR with 22Na and 36Cl, [14C]urea,
      [3H]raffinose, or tritiated water. The permeability of OMDVR to 22Na and
      [3H]raffinose was found to increase markedly and reversibly with perfusion rate.
      PNa was highly correlated with the permeability to Cl (PCl) and to [3H]raffinose
      (Praf) (R = 0.90 and 0.95, respectively) but not with Purea (R = 0.23). Praf was
      also correlated with inulin permeability (PIn) (R = 0.93). The intercepts for the
      regressions of PNa with PCl and Praf and for Praf with PIn were zero. In
      contrast, OMDVR with low PNa retained very high diffusional water permeability
      (PD) and Purea, a finding consistent with separate routes for permeation of those
      tracers. We previously established that thiourea is a competitive inhibitor of
      OMDVR urea transport. In the presence of 100 mM thiourea, OMDVR PNa and Purea
      were correlated (R = 0.71) but retained an intercept much > 0. We conclude that
      Na, Cl, raffinose, and inulin are likely to traverse the OMDVR wall through a
      common pathway, whereas specific mechanisms exist to regulate the permeation by
      urea and water.

PMID- 7631833
TI  - Role of membrane-permeable ions in renin secretion by renal juxtaglomerular
      cells.
AB  - In this study we examine the role of membrane-permeable ions in renin secretion
      from renal juxtaglomerular (JG) cells. To this end, extracellular Cl- (100
      mmol/l) in the culture medium of isolated mouse renal JG cells was replaced by
      the permeable anion NO3- or by the membrane-impermeable anion isethionate.
      Alternatively, extracellular Na+ (100 mmol/l) was substituted by the membrane
      impermeable cation choline. The effects of these ion substitutions on basal and
      stimulated renin secretion were then examined. Renin secretion was stimulated by
      the adenylate cyclase activator forskolin (10 microM), the NO donor sodium
      nitroprusside (SNP, 100 microM), the calmodulin antagonist calmidazolium (10
      microM), by lowering extracellular Ca2+ concentration ([Ca2+]e) with ethylene
      glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) (2 mM), and
      by increasing [Ca2+]e from the normal value of 0.5 to 3 mM. Substitution of
      extracellular Cl- by isethionate, but not by NO3-, inhibited basal renin release
      over 20 h of incubation. NO3- also did not change renin secretion stimulated by
      forskolin, SNP, calmidazolium, EGTA, or by increased [Ca2+]e. Isethionate, on the
      other hand, markedly attenuated the effects of EGTA and of increased [Ca2+]e, but
      not the stimulatory effect of forskolin, calmidazolium, or SNP. Substitution of
      Na+ by choline also attenuated basal renin secretion and renin secretion
      stimulated by lowering or raising [Ca2+]e. These findings suggest that, with
      respect to the dependency on permeable ions, at least two different pathways of
      regulated renin secretion from JG cells exist: a cation- and anion-dependent
      Ca(2+)-related pathway and a less ion-sensitive pathway for renin secretion
      activated by adenosine 3',5'-cyclic monophosphate and NO.

PMID- 7631834
TI  - Oxytocin as an antidiuretic hormone. II. Role of V2 vasopressin receptor.
AB  - We conducted this study to determine what receptor mediates the effect of
      oxytocin to increase osmotic water permeability (Pf) in the rat inner medullary
      collecting duct (IMCD). Reverse transcription-polymerase chain reaction (RT-PCR)
      experiments demonstrated that mRNA for both the oxytocin receptor and the V2
      receptor is present in the rat terminal IMCD. In isolated perfused IMCD segments,
      we found that the V2 vasopressin receptor antagonist [d(CH2)5(1),D
      Ile2,Ile4,Arg8]vasopressin, but not oxytocin receptor antagonists, blocked the
      hydrosmotic response to 200 pM oxytocin. The selective oxytocin receptor agonist
      [Thr4,Gly7]oxytocin did not increase water permeability. Oxytocin also increased
      urea permeability in IMCD segments. Studies in IMCD suspensions showed that
      oxytocin increases adenosine 3',5'-cyclic monophosphate production in a dose
      dependent fashion with a half-maximal (EC50) response at 5.2 nM. The dose
      response curves were virtually identical for IMCD suspensions from Sprague-Dawley
      rats and Brattleboro rats. The oxytocin dose-response curve was displaced to the
      right of the vasopressin dose-response curve (EC50, 0.44 nM). From these results,
      we conclude that the V2 receptor mediates the hydrosmotic action of oxytocin in
      rat IMCD.

PMID- 7631835
TI  - Effect of luminal angiotensin II on ammonia production and secretion by mouse
      proximal tubules.
AB  - Angiotensin II is an important regulator of acid-base and ammonia metabolism in
      the proximal tubule. Because angiotensin II receptors exist on the apical
      membrane and because luminal fluid angiotensin II concentrations may be
      substantial, the effects of luminal angiotensin II on ammonia production rates
      and net luminal total ammonia (tNH3) secretion rates were examined in dissected
      mouse S2 proximal tubule segments. Ammonia production rates reflected the total
      release of ammonia via the basolateral and luminal aspects of the tubule, whereas
      net luminal secretion rates reflected the rates at which ammonia left the tubule
      via the luminal fluid leaving the distal end of the perfused segment. The results
      demonstrated that 1) luminal angiotensin II affected tNH3 production in a
      concentration-dependent fashion, 2) luminal angiotensin II at concentrations that
      stimulated tNH3 production could counteract the effect of inhibitory basolateral
      concentrations of angiotensin II, 3) the stimulation of tNH3 production and the
      rise in intracellular calcium concentration induced by 10(-10) M luminal
      angiotensin II were blocked by the addition of an angiotensin II receptor
      inhibitor, saralasin, or the calcium channel blocker nifedipine to the luminal
      perfusion solution, and 4) in contrast to basolateral angiotensin II, which
      inhibited net luminal tNH3 secretion, luminal angiotensin II stimulated amiloride
      sensitive net luminal tNH3 secretion in parallel with stimulation of luminal
      fluid acidification. Thus luminal angiotensin II at physiological and
      superphysiological concentrations has important effects on ammonia production and
      transport in the proximal tubule that in some ways differ from the effects of
      basolateral angiotensin II.

PMID- 7631836
TI  - Characterization of Na(+)-phosphate cotransporters in renal cortical endosomes.
AB  - To determine the role of membrane recycling in proximal tubular P(i) transport,
      we studied the transport functions of simultaneously prepared rat renal cortical
      endosomal vesicles (EV) and brush-border membrane vesicles (BBMV). Initial P(i)
      uptake was Na+ gradient-dependent in both vesicles. Kinetic studies showed a
      lower apparent maximal rate (Vmax) for P(i) uptake in EV compared with BBMV (446
      +/- 69 vs. 1493 +/- 117 pmol.mg protein-1 x 15 s-1, respectively; n = 4, P <
      0.05), with no difference in the apparent Michaelis constant (Km). Endosomal
      Na(+)-P(i) cotransport was inhibited by phosphate analogues, phosphonoformic acid
      and arsenate, but not by the anion-exchange inhibitor, 4,4'
      diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). Na(+)-P(i) cotransport was
      electroneutral in both vesicles, with a stoichiometry of 2 for BBMV and 1 for EV.
      The nonpermeant sulfhydryl reagent, 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB),
      produced a marked inhibition of Na(+)-P(i) cotransport in EV but not in BBMV,
      suggesting accessible sulfhydryl groups, an "inside-out" orientation in EV, and
      "right-side-out" orientation in BBMV. The EV and the BBMV differed significantly
      in their phospholipid composition and lipid fluidity. The Na(+)-P(i)
      cotransporter protein (NaPi-2) abundance, determined by Western blots, was five
      times lower in EV than in BBMV (0.25 +/- 0.05 vs. 1.36 +/- 0.20 arbitrary units).
      Renal cortical endosomes contain Na(+)-P(i) cotransporters, albeit at a lower
      density, suggesting involvement of membrane recycling in the regulation of
      proximal tubular P(i) transport.

PMID- 7631837
TI  - Cholesterol feeding enhances vasoconstrictor effects of products from rabbit
      polymorphonuclear leukocytes.
AB  - We have studied the vasoactive properties of products released from rabbit
      polymorphonuclear leukocytes (PMNs) before and after short-term (4 and 8 wk)
      dietary supplementation with 1% cholesterol. Plasma cholesterol levels were
      similar after 4 and 8 wk of cholesterol diet, whereas gross atherosclerotic
      lesions were present at 4 wk but significantly more extensive after 8 wk. PMN
      products from all rabbits caused endothelium-dependent contraction of isolated,
      control (nonatherosclerotic) rabbit aorta submaximally contracted with
      phenylephrine. However, both 4 and 8 wk of cholesterol feeding resulted in
      equivalent contractions by PMN products, which were significantly greater than
      contractions by control PMNs. Endothelium-dependent contraction (by PMN products)
      and relaxation (by acetylcholine) were attenuated by 8 wk of cholesterol feeding.
      PMN products attenuated acetylcholine-induced relaxation of aorta from
      cholesterol-fed rabbits and of control aorta treated with phenoxybenzamine to
      reduce muscarinic receptor reserve. We conclude that elevation of plasma
      cholesterol results in increased release of a PMN product(s) that causes
      endothelium-dependent constriction.

PMID- 7631838
TI  - Lack of a role of adenosine in activation of ischemically sensitive cardiac
      sympathetic afferents.
AB  - Adenosine has been implicated in the pathogenesis of cardiac pain through
      activation of cardiac sympathetic afferents. The present study was performed to
      assess directly the contribution of adenosine in activating ischemically
      sensitive cardiac sympathetic afferents. Single-unit activity of ischemically
      sensitive afferents located in both ventricles was recorded from the left
      thoracic sympathetic chain or rami communicantes of anesthetized cats during 5
      min of myocardial ischemia. Intracardiac injection (5 mg) or epicardial
      application (1-5 mg/ml) of adenosine onto the receptive fields failed to activate
      31 ischemically sensitive A delta- and C fiber afferents, which were responsive
      to topical application of bradykinin (10 micrograms/ml). Intracardiac injection
      (5 mg) or topical application (1-5 mg/ml) of an adenosine A1 receptor agonist, N6
      cyclopentyladenosine, also did not increase the discharge activity of 13 other
      ischemically sensitive C fiber afferents. Treatment with dipyridamole (1 mg/kg
      iv) to inhibit the cellular uptake of adenosine did not significantly potentiate
      the response of 10 separate C fiber afferents to 5 min of myocardial ischemia.
      Furthermore, blockade of adenosine receptors with aminophylline (5 mg/kg iv) did
      not significantly attenuate the response of 10 other C fiber afferents to 5 min
      of myocardial ischemia. The results of the present study demonstrate that
      exogenous and endogenous adenosine do not contribute to activation of
      ischemically sensitive cardiac sympathetic afferents. The findings of the present
      study fail to support a substantial role for adenosine and its A1 receptors in
      activation of cardiac sympathetic afferents during myocardial ischemia.

PMID- 7631839
TI  - Effects of adenosine in simulated ischemia and reperfusion in guinea pig
      ventricular myocytes.
AB  - Effects of adenosine (ADN) on cardiac cellular electrical and contractile
      activity were determined during ischemia and reperfusion. Electrical activity was
      recorded with conventional and voltage-clamp techniques. Contractions were
      monitored with a video edge detector. Myocytes were exposed to simulated ischemia
      (20 min), in the presence or absence of ADN (1-50 microM), and reperfused with
      Tyrode solution. ADN had no effects under control conditions. However, action
      potential abbreviation during ischemia was greater in the presence of ADN than
      for control, and recovery was delayed. In ischemia, Ca2+ current declined
      equally, and contractions were abolished in control and ADN-treated myocytes. In
      early reperfusion, oscillatory afterpotentials (OAP), transient inward current
      (ITI) and aftercontractions appeared, and contractions increased above
      preischemic levels. ADN abolished contractile overshoot and reduced incidence of
      OAP, ITI, and aftercontractions from 78 to 37.5%. The effects of exogenous ADN
      were inhibited by ADN A1-receptor blockade. Inhibition of endogenous ADN by 8
      phenyltheophylline only increased incidence of ITI. Thus exogenous ADN in
      ischemia may protect the myocardium in reperfusion via A1 receptors.

PMID- 7631840
TI  - Circadian aspects of apparent correlation dimension in human heart rate dynamics.
AB  - The purpose of this study was to examine changes in complexity of cardiac
      dynamics over 24 h. With use of Holter monitoring, 27 24-h electrocardiogram
      recordings were obtained from 15 healthy subjects. For each recording, the
      apparent dimension (DA) was calculated for consecutive sections of 500
      heartbeats. These were used to determine nighttime and daytime dimension (D(An)
      and D(Ad), respectively) as well as the difference between D(An) and D(Ad) (delta
      DA). Mean 24-h DA, D(An), and D(Ad) were 5.9 +/- 0.3, 6.3 +/- 0.5, and 5.6 +/-
      0.6, respectively. D(An) was significantly higher than D(Ad) (P < 0.001), with a
      mean delta DA of 0.6 +/- 0.7. Furthermore, 67% of delta DA values were
      significantly different from zero at the 0.05 level. The results show that
      dimension analysis may be applied to heart rate dynamics to reveal circadian
      differences of heart rate complexity. We suggest that the decreased complexity
      during daytime may result from the synchronization of physiological functions.
      The increase in complexity at night would then correspond to an uncoupling of
      these functions during the regenerative period.

PMID- 7631841
TI  - Central cardiovascular effects induced by intracisternal PACAP in dogs.
AB  - The cardiovascular responses to intracisternally administered pituitary adenylate
      cyclase-activating polypeptide (PACAP) were investigated and compared with those
      of vasoactive intestinal peptide (VIP) in anesthetized dogs. Intracisternal
      administration of 10 nmol of PACAP-27 increased mean arterial blood pressure
      (MABP) significantly with a simultaneous increase of plasma arginine vasopressin
      and epinephrine concentrations. Intracisternal administration of VIP increased
      plasma arginine vasopressin concentration significantly but caused no appreciable
      change in MABP. Systemic infusion of the nonpeptide vasopressin V1 receptor
      antagonist OPC-21268 did not inhibit the PACAP-27-induced increase in MABP,
      whereas phentolamine, an alpha-adrenoceptor blocker, reversed the increase.
      Intracisternal pretreatment with the vasopressin V1 receptor antagonist [Pmp1,
      Tyr(Me)2]Arg8-vasopressin also inhibited the increase. These findings suggest
      that PACAP has a central pressor action by increasing sympathetic outflow, which
      is probably mediated by the vasopressinergic neural network. PACAP seems to play
      important roles in hormonal and neural control of systemic circulation.

PMID- 7631842
TI  - 4-Hydroxynonenal, a novel indicator of lipid peroxidation for reperfusion injury
      of the myocardium.
AB  - 4-Hydroxynonenal (HNE) has been proposed as an important marker of radical
      induced lipid peroxidation (LPO) during postischemic reperfusion injury of the
      myocardium. Therefore, the liberation of HNE into the effluent of isolated
      perfused rat hearts was investigated. For the first time, the formation of the
      aldehyde is demonstrated in myocardium. During control perfusion, 1.28 +/- 0.33
      pmol HNE.min-1.mg protein-1 were formed by the hearts of 18-mo-old Wistar-Kyoto
      (WKY) rats and 2.74 +/- 1.12 pmol.min-1.mg protein-1 by those of 18-mo-old
      spontaneously hypertensive (SHR) rats, respectively. In the WKY group, HNE
      release increased to 3.35 +/- 1.13 pmol.min-1.mg protein-1 2 min after the onset
      of reperfusion following 30 min of total and global ischemia compared with the
      preischemic control period (P < 0.05). In the SHR group, HNE liberation was
      higher during reperfusion (8.66 +/- 1.33 pmol.min-1.mg protein-1, maximum at 2
      min reperfusion) compared with both the respective preischemic control and the
      respective reperfusion interval of the WKY group (P < 0.05 each). The SHR rats
      showed signs of congestive cardiac failure of a decompensated hypertrophy in
      comparison to the normotensive WKY rats. Moreover, the SHR rat hearts exhibited a
      lower release of adenine nucleotide degradation products (adenine, inosine,
      hypoxanthine plus uric acid: 48.1 +/- 10.2 nmol.30 min-1.mg protein-1; P < 0.05)
      and a diminished functional recovery (left ventricular developed pressure, 32 +/-
      16 mmHg; P < 0.05) during 30 min of reperfusion compared with the WKY group (77.9
      +/- 14.4 nmol.30 min-1.mg protein-1; 90 +/- 21 mmHg).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7631844
TI  - Effects of renal denervation on cardiovascular response to furosemide in
      conscious lambs.
AB  - The cardiovascular response to furosemide in the newborn and the role of renal
      sympathetic nerves in influencing this response have not been investigated. We
      hypothesized that in conscious lambs, furosemide would decrease blood pressure,
      the response being accentuated in the absence of renal sympathetic nerves.
      Pulsatile pressures and heart rates were measured before and after furosemide (2
      mg/kg) administration to chronically instrumented lambs with either bilateral
      renal denervation (denervated, n = 8) or renal nerves intact (intact, n = 6). In
      intact lambs, mean arterial pressure remained constant after furosemide; in
      denervated lambs there was an increase in arterial pressure 20 min after
      furosemide (P < 0.001), and control levels were reached by 100 min. Basal heart
      rate was higher in denervated than in intact lambs (P = 0.009). In both groups of
      lambs, heart rate increased 40 min after furosemide and remained elevated. These
      data provide new information that, in conscious newborn animals, renal
      sympathetic nerves influence the blood pressure response to furosemide, as well
      as basal control of heart rate.

PMID- 7631843
TI  - Timing of sympathetic innervation affects growth of myocardium in oculo.
AB  - The effects of sympathetic innervation on myocardial growth during the
      proliferative and hypertrophic phases of cardiac growth were examined with the
      use of embryonic day 12 whole hearts or ventricles cultured in the anterior eye
      chamber of adult rats for 8 wk. Sympathetic innervation of whole heart and
      ventricular grafts was prevented by removing the superior cervical ganglion 1 wk
      before grafting or was limited to the cellular proliferation phase of growth by
      superior cervical ganglionectomy after grafts had been in oculo for 4 wk. Grafts
      in sympathetically innervated eye chambers were significantly larger than grafts
      in eye chambers denervated at 4 wk and grafts in eye chambers sympathectomized 1
      wk before grafting. Innervation of grafts was delayed until 5-6 wk in oculo by
      crushing the internal carotid nerve. Delayed innervation produced grafts that
      were as large as those in innervated eye chambers. Together, these experiments
      suggest that the effects of sympathetic innervation on myocardial growth in oculo
      are most apparent during the second 4 wk in oculo (i.e., during the cellular
      enlargement phase of growth.

PMID- 7631845
TI  - Cardiac responses to induced lactate oxidation: NMR analysis of metabolic
      equilibria.
AB  - The role of lactate as a source of pyruvate oxidation in supporting cardiac work,
      energetics, and formation of oxidative metabolites was examined in normal
      myocardium. 13C- and 31P-nuclear magnetic resonance (NMR) spectra were acquired
      from isolated rabbit hearts supplied 2.5 mM [3-13C]lactate or [3-13C]pyruvate
      with or without stimulation of pyruvate dehydrogenase (PDH) by dichloroacetate
      (DCA). Similar workloads determined by rate-pressure products were noted with
      pyruvate (21,700 +/- 2,400; mean +/- SE) and lactate (18,970 +/- 1,510). Oxygen
      consumption was similar in all four groups with means between 19.0 and 22.2
      mumol.min-1.g dry weight-1 (SE = 1.6-2.0) as was the ratio of phosphocreatine to
      ATP with means between 1.8 and 2.1 (SE = 0.1-0.6). Intracellular pH, determined
      from 31P-NMR spectra, was essentially the same with pyruvate (7.06 +/- 0.02) and
      lactate (7.05 +/- 0.04). 13C enrichment of glutamate was higher with lactate
      (92%) than with pyruvate (70%). Pyruvate plus DCA induced no change in glutamate
      content at 9-10 mumol/g, but 13C enrichment increased to 83%, while lactate plus
      DCA maintained enrichment at 90%. Levels of alpha-ketoglutarate were lower with
      lactate (1.81 mumol/g) than with pyruvate (2.36 mumol/g). Lactate plus DCA
      elevated glutamate by 60% with a proportional increase in alpha-ketoglutarate.
      Thus the balance between glutamate and alpha-ketoglutarate was affected by
      substrate supply only and not by PDH activation. The results suggest that the
      equilibrium between alpha-ketoglutarate and glutamate is sensitive to cytosolic
      redox state, an important consideration for 13C-NMR analyses that rely on
      glutamate.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7631846
TI  - Mechanism of mechanical alternans in ischemia-reperfusion: role of deficient
      relaxation of the strong twitch.
AB  - We tested the hypothesis that impaired and incomplete relaxation of the strong
      twitch of mechanical alternans causes the peak force deficit (PFD) of the weak
      twitch and that, by decreasing the relaxation deficit (RD) of the strong twitch,
      dobutamine would diminish the PFD. We studied isometric twitches of the in situ
      blood-perfused canine papillary muscle (n = 8). To produce mechanical alternans,
      we paced the heart at 110-155 beats/min and decreased mean coronary perfusion
      pressure (MCPP) stepwise to produce ischemia and then increased it to produce
      reperfusion. We measured the RD and PFD and fit each curve of isometric force
      [F(t)] with the relation F(t) = F0 + C(t/A)Be1-(t/A)B, where F0 is force at
      twitch onset, to obtain the parameters A, B, and C. B is a dimensionless index of
      myocardial relaxation; it decreases with impaired (delayed) relaxation. At each
      MCPP, we averaged B for the strong and weak twitches. The PFD showed a positive
      correlation with the RD. At each MCPP, mean B was lower for the strong twitch
      than for the weak twitch, indicating impaired relaxation of the strong twitch.
      Dobutamine increased B from 1.83 +/- 0.14 to 2.12 +/- 0.16 (P = 0.00002) in the
      strong twitch and decreased B from 4.15 +/- 2.42 to 2.19 +/- 0.18 (P = 0.05) in
      the weak twitch. Dobutamine thus equalized the relaxation of the strong and weak
      twitches. Consequently it decreased the RD from 2.57 +/- 2.14 to 0.16 +/- 0.24 g
      (P = 0.01) and the PFD from 5.50 +/- 3.67 to 1.04 +/- 1.15 g (P = 0.01).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7631847
TI  - Regional epinephrine kinetics in human heart failure: evidence for extra-adrenal,
      nonneural release.
AB  - A number of neurohumoral processes are activated in heart failure, including an
      increase in the plasma concentration of epinephrine. Radiotracer methods were
      applied in 42 patients with severe heart failure and 31 healthy volunteers to
      ascertain the rate at which epinephrine is released to plasma and to evaluate the
      contribution of extra-adrenal sources. The increase in arterial plasma
      epinephrine observed in the heart failure patients was explained principally by a
      34% (P < 0.001) reduction in the whole body clearance rate of epinephrine from
      plasma. Regional venous sampling from the heart, lungs, and hepatomesenteric beds
      was performed in a subgroup of the study population, revealing a significant
      increase in the release rate of epinephrine to plasma from these organs in heart
      failure which accounted for 26% of the whole body plasma epinephrine appearance
      rate. To establish whether the cardiac epinephrine release was of neuronal
      origin, a physical (cycling) or mental (difficult mental arithmetic) stressor was
      applied as a sympathoexcitatory stimulus, given that a proportional release of
      norepinephrine and epinephrine could be expected if sympathetic nerves were the
      source. These interventions caused significant increases in the regional
      spillover of norepinephrine to plasma but not that of epinephrine. These findings
      suggest that nonadrenal tissues contribute significantly to the whole body
      epinephrine release rate in heart failure and that this may arise from a site
      other than sympathetic neurons.

PMID- 7631848
TI  - Dissociation of endothelial cell dysfunction and blood pressure in SHR.
AB  - This study was designed to examine the impairment of endothelium-dependent
      relaxation in spontaneously hypertensive rats (SHR), to determine whether
      endothelial cell function is normalized by in vivo treatment with a thromboxane
      A2-prostaglandin endoperoxide (TP)-receptor blocker, and to establish whether
      endothelial dysfunction contributes to the elevated blood pressure. In isolated
      aortic rings from SHR, endothelium-dependent relaxations caused by acetylcholine,
      adenosine diphosphate, and alpha-thrombin were markedly impaired compared with
      those from Wistar-Kyoto (WKY) normotensive rats. Arachidonic acid-induced
      contractions were significantly enhanced in aorta from SHR. In contrast,
      relaxations caused by direct smooth muscle vasodilators, nitroprusside and
      cromakalim, and contractions caused by U-46619 were not different between SHR and
      WKY rats. Treatment of SHR with the oral TP-receptor antagonist, ifetroban, at 20
      and 50 mg.kg-1.day-1 fully restored endothelium-dependent relaxation toward
      normal. However, ifetroban produced no effect on blood pressure in SHR. In vitro
      incubation of aortic rings from SHR with ifetroban also normalized relaxations to
      acetylcholine but had no effect in aorta from WKY. In contrast, the thromboxane A
      synthase inhibitor, dazoxiben, only partially improved abnormal acetylcholine
      induced relaxations in aorta from SHR. The results demonstrate that endothelial
      cell dysfunction in hypertension can be restored to normal by selective TP
      receptor blockade. Furthermore, endothelial cell dysfunction and TP-receptor
      activation may not significantly contribute to elevated systemic blood pressure
      in SHR.

PMID- 7631849
TI  - GTP requirement for isoproterenol activation of calcium channels in vascular
      myocytes.
AB  - The effects of activating the beta-adrenoceptor pathway on calcium current (ICa)
      in rabbit portal vein (PV) were studied in myocytes freshly isolated by
      collagenase and elastase treatment. ICa was measured at room temperature (20
      degrees C) using whole cell, voltage-clamp methods from a holding potential of 
      60 mV in cells dialyzed with a pipette solution containing (mM) 100 CsCl, 20
      tetraethylammonium chloride, 5 NaCl, 5 MgATP, 20 N-2-hydroxyethylpiperazine-N'-2
      ethanesulfonic acid (HEPES), and 10 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'
      tetraacetic acid (BAPTA). The cells were superfused with a solution containing
      (mM) 140 NaCl, 5 KCl, 1 MgCl2, 5 CaCl2, 10 HEPES, and 10 glucose. Only L-type ICa
      was present in these myocytes, averaging 3.5 +/- 0.3 pA/pF at +10 mV under
      control conditions. With 0.1 mM guanosine 5'-triphosphate (GTP) added to the
      pipette solution, 1 microM isoproterenol (Iso) or forskolin (Fsk) uniformly
      increased ICa: Iso by 45 +/- 5% and Fsk by 88 +/- 11%. This augmentation of ICa
      was not associated with significant changes in the voltage dependence of
      activation or inactivation but was associated with a small increase in the rate
      of inactivation of ICa. Fsk was also associated with an increased rate of ICa
      activation. The Iso effect was blocked by pretreatment with 1 microM propranolol
      and reversed by propranolol after Iso exposure. The ICa response to 10 microM Iso
      or Fsk was smaller than the response to 1 microM, with some cells showing a
      steady-state reduction in ICa. When the latter occurred, the voltage dependence
      of availability was shifted to the left by 5 +/- 0.4 mV.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7631850
TI  - Cytoskeleton modulates gating of voltage-dependent sodium channel in heart.
AB  - To investigate the role of the cytoskeleton in cardiac Na+ channel gating, the
      action of cytochalasin D (Cyto-D), an agent that interferes with actin
      polymerization, was studied by whole cell voltage clamp and cell-attached and
      inside-out patches from rat and rabbit ventricular cardiac myocytes. Cyto-D (20
      40 microM) reduced whole cell peak Na+ current by 20% within 12 min and slowed
      current decay without affecting steady-state voltage-dependent availability or
      recovery from inactivation. Brief treatments (< 10-15 min) of cell-attached
      patches by Cyto-D (20 microM) in the bath induced short bursts of Na+ channel
      openings and prolonged decays of ensemble-averaged currents. Bursting of the Na+
      channel was more pronounced when the cell suspension was pretreated with Cyto-D
      (20 microM) for 1 h before seal formation. Application of Cyto-D on the
      cytoplasmic side of inside-out patches resulted in more dramatic gating changes.
      Peak open probability was reduced by > 50% within 20 min, and long bursts of
      openings occurred. Washout of Cyto-D did not restore ensemble-averaged current
      amplitude, but burst duration decreased toward control values. Cyto-D also
      induced an additional slower component to open and closed times. These results
      suggest that Cyto-D, through effects on cytoskeleton, induced cardiac Na+
      channels to enter a mode characterized by a lower peak open probability but a
      greater persistent activity as if the inactivation rate was slowed. The
      cytoskeleton, in addition to localizing integral membrane proteins, apparently
      also plays a role in regulating specific detailed functions of integral membrane
      proteins such as the gating of Na+ channels.

PMID- 7631851
TI  - In vivo production of nitric oxide correlates with NMDA-induced cerebral
      hyperemia in newborn sheep.
AB  - Stimulation of N-methyl-D-aspartate (NMDA) receptors in brain increases nitric
      oxide production in vitro. We tested the hypothesis that nitric oxide
      participates in the increase in local cerebral blood flow (CBF) caused by
      infusion of NMDA in anesthetized newborn sheep. We used the combined hydrogen
      clearance and microdialysis technique for simultaneous measurement of local CBF,
      infusion of drugs, and measurement of interstitial levels of L-[14C]citrulline in
      the parietal cortex. Release of L-[14C]citrulline into the dialysate during
      continuous infusion of L-[14C]arginine was used as a marker of nitric oxide
      production in vivo. Citrulline recovery and CBF were measured hourly during a 4-h
      infusion of cerebrospinal fluid containing either 1) no additional drugs, 2) 1 mM
      NMDA, 3) 1 mM NG-nitro-L-arginine methyl ester (L-NAME, a nitric oxide synthase
      inhibitor), 4) 1 mM NMDA + 1 mM L-NAME, 5) 0.1 mM 2-chloroadenosine (adenosine
      receptor agonist), or 6) 0.1 mM 2-chloroadenosine + 1 mM L-NAME. At 240 min of
      perfusion, CBF (ml.min-1.100 g-1; means +/- SE) was as follows: control 52 +/- 3,
      NMDA 116 +/- 11, L-NAME 32 +/- 5, NMDA+L-NAME 40 +/- 4,2-chloroadenosine 201 +/-
      63, and 2-chloroadenosine+L-NAME 129 +/- 18. Citrulline recovery (fmol/min) at
      240 min of perfusion was as follows: control 38 +/- 12, NMDA 149 +/- 21, L-NAME 9
      +/- 1, NMDA+L-NAME 39 +/- 5, 2-chloroadenosine 13 +/- 5, and 2-chloroadenosine+L
      NAME 17 +/- 1.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7631853
TI  - Pentoxifylline inhibits FMLP-induced macromolecular leakage.
AB  - The acute inflammatory responses to the chemotactic peptide N-formyl-methionyl
      leucyl-phenylalanine (FMLP) and the effects of pentoxifylline (PTXF) on the
      responses in vivo were studied. We used intravital microscopy with rat cremaster
      muscle preparation to determine inflammatory responses of microcirculation.
      Macromolecular leakage from postcapillary venules was evaluated by quantifying
      the extravasation of fluorescein isothiocyanate conjugated to bovine serum
      albumin. FMLP induced a rapid increase in macromolecular leakage, an increase in
      leukocyte-endothelium adhesion, and a decrease in blood flow in the
      microcirculation. PTXF inhibited FMLP-induced responses in a dose-dependent
      manner but failed to block the histamine-dependent leakage induced by compound
      48/80. In addition, diphenhydramine, a histamine-receptor blocker, did not affect
      the macromolecular leakage induced by FMLP. The cell-permeable adenosine 3',5'
      cyclic monophosphate (cAMP) analogue N6,2'-O-dibutyryladenosine 3',5'-cyclic
      monophosphate mimicked PTXF's effects on the microcirculation and also inhibited
      FMLP-induced macromolecular leakage. PTXF is known to inhibit phosphodiesterase
      and increase intracellular cAMP, which modulates functions of endothelial cells,
      smooth muscle cells, and neutrophils in vitro. Our findings suggest that FMLP
      induces acute inflammatory responses through activation of neutrophils,
      independent of endogenous histamine release, and that PTXF inhibits these
      responses through elevated intracellular cAMP.

PMID- 7631852
TI  - Arginine-nitric oxide pathway and cerebrovascular regulation in cortical
      spreading depression.
AB  - Nerve cells release nitric oxide (NO) in response to activation of glutamate
      receptors of the N-methyl-D-aspartate (NMDA) subtype. We explored the hypothesis
      that NO influences the changes of cerebral blood flow (CBF) during cortical
      spreading depression (CSD), which is known to be associated with NMDA receptor
      activation. CBF was monitored in parietal cortex by laser-Doppler flowmetry in
      halothane-anesthetized rats. Under control conditions, CSD induced regular
      changes of CBF, which consisted of four phases: a brief hypoperfusion before the
      direct current (DC) shift; a marked CBF rise during the DC shift; followed by a
      smaller, but protracted increase of CBF; and a prolonged CBF reduction (the
      oligemia). NO synthase inhibition by intravenous and/or topical application of NG
      nitro-L-arginine enhanced the brief initial hypoperfusion, but the CBF increases
      and the oligemia were unchanged. L-Arginine prevented the development of the
      prolonged oligemia after CSD but had no influence on the marked rise of CBF
      during CSD. Animals treated with L-arginine recovered the reduced vascular
      reactivity to hypercapnia after CSD much faster than control rats. Functional
      denervation of cortical and pial arterioles by tetrodotoxin accentuated the pre
      CSD hypoperfusion and the oligemia but did not affect the CBF increases. The
      results suggest that NO is important for the changes of cerebrovascular
      regulation following CSD. The observations may have clinical importance, since
      CBF changes during migraine may be triggered by CSD.

PMID- 7631854
TI  - Effects of moderate repetitive ischemia on myocardial substrate utilization.
AB  - The purpose of this report was to directly measure the influence of antecedent
      ischemia or repetitive ischemia on subsequent rates of intermediary metabolism,
      specifically exogenous glucose utilization and fatty acid oxidation, with the use
      of myocardial equilibrium labeling with [U-14C]palmitate and [5-3H]glucose.
      Twenty-one intact, working, extracorporeally perfused pig hearts were prepared
      and divided into three groups. These groups included 7 control hearts and 14
      comparison hearts, which were exposed to either one cycle (cycle 1, n = 7) or
      four cycles (cycle 4, n = 7) of brief (5-10 min), moderate (70% decrease in flow
      below aerobic values) precursory ischemia to the left anterior descending (LAD)
      circulation followed by aerobic reperfusion. All groups then underwent a 40 min
      sustained LAD ischemia (60% decrease in flow below aerobic levels) and 40 min
      aerobic reperfusion. Treatment with one cycle of transient ischemia did not
      significantly modify the pattern of glycolytic flux from control values during
      sustained ischemia (over a ninefold increase in average control and cycle 1
      values above aerobic levels). However, repetitive ischemia in cycle 4 hearts
      demonstrably attenuated glycolytic flux during the same interval (-45% from
      control hearts, P < 0.046). Glucose utilization rapidly returned to near-aerobic
      values in all three groups during reperfusion but was again appreciably lower (P
      < 0.004 from control values) in cycle 4 hearts. Fatty acid oxidation averaged
      12.3 +/- 1.2 mumol.h-1.g dry wt-1 in all three groups during sustained ischemia
      and 21.3 +/- 2.0 mumol.h-1.g dry wt-1 during reperfusion (not significant among
      groups for either perfusion interval).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7631855
TI  - Inhibition of vascular nitric oxide-cGMP pathway by plasma from ischemic hindlimb
      of rats.
AB  - The hypothesis was tested that plasma from ischemic hindlimbs facilitates
      hypertension. Ischemia-induced hypertension was generated in rats by infrarenal
      aortic cross clamping for 5 h after which plasma was obtained from femoral vein
      blood. In vitro contractile activity of naive aortic rings incubated for 2 h in
      plasma collected from ischemic rats demonstrated reduced relaxation to
      acetylcholine and nitroglycerin. Methylene blue (10(-5) M) induced greater
      contraction in rings incubated in control vs. ischemic plasma, suggesting that
      endogenous guanylate cyclase activity is decreased by ischemic plasma. However, 8
      bromo-guanosine 3',5'-cyclic monophosphate (cGMP) relaxed equally strips
      incubated in ischemic or control plasma. Acetylcholine-induced nitrite release
      was significantly lower in ischemic vs. control plasma-incubated strips (8.6 +/-
      2.7 vs. 28.2 +/- 2.3 ng/10 mg tissue wt, respectively). The impaired relaxation
      to acetylcholine in ischemic plasma-incubated rings was significantly increased
      by L-arginine but not by prior treatment of ischemic plasma with heating or
      superoxide dismutase and catalase. These findings suggest the impaired relaxation
      is mediated through inhibition of the nitric oxide-cGMP pathway. Prolonged
      blunting of vasodilation by ischemic plasma may therefore contribute to
      maintenance of a sustained vasoconstriction and ischemic hypertension.

PMID- 7631856
TI  - Depressed regional deformation near anterior papillary muscle.
AB  - The role of the papillary muscle in left ventricular function has received new
      attention. We hypothesized that regional mechanics of the left ventricular wall
      near the anterior papillary muscle are influenced by the papillary muscle
      insertion. We therefore studied three-dimensional regional mechanics in and near
      the anterior papillary muscle in anesthetized, open-chest dogs, using implanted
      radiopaque markers and biplane cineradiography. In seven dogs, deformation
      differed little between an anterior papillary muscle insertion site (PMA) and a
      more basal site (PMB) overlying the anterior papillary muscle. However, local
      shortening and wall thickening were depressed in both locations relative to
      anterior free wall sites (FWA, FWB) studied in five additional dogs. A distinct
      structural border was observed at the junction between the myocardial wall and
      anterior papillary muscle, which may preclude the use of homogeneous strain in
      that region. Data from within the anterior papillary muscle indicated that
      uniaxial measurements in the papillary muscle are extremely sensitive to the
      orientation of the measurement axis, possibly explaining the variety of papillary
      muscle shortening patterns reported by previous investigators.

PMID- 7631857
TI  - Effect of exercise on coronary pressure-flow relationship in hypertrophied left
      ventricle.
AB  - Left ventricular (LV) hypertrophy (LVH) secondary to chronic pressure overload is
      associated with increased susceptibility to myocardial hypoperfusion and ischemia
      during exercise. The present study was performed to determine whether exercise
      causes alterations in minimum coronary resistance or effective back pressure
      [coronary pressure at zero flow (Pzf)] that limit maximum myocardial perfusion in
      the hypertrophied heart. Ascending aortic banding in 7 dogs increased the LV
      weight-to-body weight ratio to 7.7 +/- 0.3 g/kg compared with 4.6 +/- 0.2 g/kg in
      11 normal dogs (P < 0.01). Maximum coronary vasodilation was produced by
      intracoronary infusion of adenosine. Under resting conditions, the slope of the
      pressure-flow relationship (conductance) was significantly lower in the LVH
      animals than in the normal dogs (7.2 +/- 0.8 vs. 11.9 +/- 0.8 x 10(-2) ml.min-1.g
      1.mmHg-1; P < 0.01); the slope correlated with the degree of hypertrophy r =
      0.74; P < 0.001). The Pzf measured during total coronary artery occlusion
      (Pzf,measured) was significantly elevated in LVH compared with normal dogs (25.6
      +/- 2.2 vs. 13.0 +/- 1.2 mmHg; P < 0.01); Pzf,measured was positively correlated
      (r = 0.78, P < 0.0005) with LV end-diastolic pressure measured during total
      coronary artery occlusion (9.0 +/- 1.1 mmHg in normal dogs and 22.2 +/- 3.2 mmHg
      in LVH dogs; P < 0.01). Graded treadmill exercise to maximum heart rates of 210
      +/- 9 and 201 +/- 8 beats/min in normal and LVH animals, respectively, caused
      similar decreases in the slope of the pressure-flow relationship in LVH (from 7.7
      +/- 0.9 to 6.1 +/- 0.8 x 10(-2) ml.min-1.g-1.mmHg-1; P < 0.01) and normal dogs
      (from 11.9 +/- 0.8 to 10.0 +/- 0.7 x 10(-2) ml.min-1.g-1.mmHg-1; P < 0.01).
      However, exercise-induced increases in Pzf,measured were significantly greater in
      the LVH animals (from 25.6 +/- 2.2 to 40.8 +/- 2.1 mmHg; P < 0.01) than in normal
      animals (from 13.0 +/- 1.2 to 24 +/- 2.1 mmHg; P < 0.01) (P < 0.01 LVH vs.
      normal). The greater increase in Pzf paralleled a more pronounced increase in LV
      end-diastolic pressure in the LVH dogs from 22.2 +/- 3.2 to 39.1 +/- 2.7 mmHg)
      than in normal dogs from 9.0 +/- 1.1 to 14.2 +/- 2.0 mmHg). The results suggest
      that exaggerated increases in filling pressure during exercise in the
      hypertrophied left ventricles contributed to impairment of myocardial perfusion
      during exercise by augmenting the back pressure, which opposes coronary
      flow.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7631858
TI  - Adenosine modulates hypoxia-induced atrial natriuretic peptide release in fetal
      sheep.
AB  - The effects of adenosine on atrial natriuretic peptide (ANP) secretion were
      determined in chronically catheterized fetal sheep (> 0.8 term). Adenosine was
      infused into the the right jugular vein for 1 h at 8 +/- 0.4 (5 fetuses), 160 +/-
      8 (6 fetuses), and 344 +/- 18 micrograms.min-1.kg estimated fetal wt-1. Fetal
      arterial blood gases and pH were generally unaffected by adenosine, although mean
      arterial CO2 tension increased transiently by 2-5 Torr and pH fell progressively
      during the highest rate of infusion. During the intermediate and high infusion
      rates, fetal hemoglobin concentrations increased by 11-13% and mean fetal heart
      rate rose by 18% from a control value of approximately 167 beats/min. Mean
      arterial pressure was not affected during adenosine infusion. Adenosine
      significantly increased fetal plasma ANP levels, with maximum concentrations
      1.80, 2.36, and 2.51 times greater than control means (142-166 pg/ml) for the
      respective infusion rates of 8, 160, and 344 micrograms.min-1.kg estimated fetal
      wt-1. In seven fetuses, reducing fetal arterial O2 tension by approximately 9-10
      Torr from a control of 23 +/- 1.3 Torr increased plasma ANP concentrations
      approximately 2.4 times the control mean of 176 pg/min. Adenosine-receptor
      blockade with 8-(p-sulfophenyl)-theophylline reduced by 50% the maximum hypoxia
      induced rise in plasma ANP concentrations. It is concluded that adenosine causes
      a dose-dependent rise in fetal plasma ANP concentrations and modulates fetal ANP
      release during hypoxia.

PMID- 7631859
TI  - Noninvasive measurements of albumin flux into lung interstitium with increased
      microvascular pressure.
AB  - The purpose of this study was to determine the effect of increasing left atrial
      pressure on noninvasive measurements of radiolabeled albumin normalized slope
      index (NSI). Using portable gamma scintillation detectors, we monitored
      radioactivities of 131I-labeled albumin and 51Cr-labeled red blood cells in the
      blood and over the lung of six anesthetized sheep before and 2 h after a 9- to 14
      Torr increase in left atrial pressure. Measurements of NSI for 131I-albumin
      decreased > 50% after a step increase in left atrial pressure. We interpreted the
      data using a model that has been used to successfully describe unsteady-state
      lymph flow and protein concentrations after vascular pressure increases in sheep.
      Model predictions strongly suggest that the reduction in NSI is due to rapid
      fluid and solute removal from the interstitium via the lymphatics. The
      theoretical model was able to predict external scan data and lung lymph protein
      concentrations only when a change in lymphatic conductance (LI) or initial
      lymphatic pressure (P0) was imposed at the time of increased pressure. On
      average, model-predicted increases in LI were sevenfold, whereas predicted
      decreases in P0 were four- to fivefold. Imposed changes in LI and P0 opposed
      increases in interstitial fluid volume after increased pressure. This was
      consistent with normal-to-low postmortem measurements of bloodless wet-to-dry
      lung weight ratios. In summary, these results indicate that changes in the rate
      of fluid removal from the interstitium can significantly alter NSI, and in this
      case, NSI does not reflect pulmonary microvascular permeability. In sheep,
      increases in the lymphatics' ability to remove interstitial fluid may occur with
      relatively small increases in microvascular pressure.

PMID- 7631860
TI  - Modulation of cardiac Na(+)-K+ pump current: role of protein and nonprotein
      sulfhydryl redox status.
AB  - Oxidant stress alters protein structure and function, possibly through the
      modification of the redox status of regulatory protein sulfhydryl groups. We used
      the sulfhydryl-blocking reagent p-chloromercuriphenylsulfonic acid (pCMPSA),
      applied selectively and independently to either the intracellular or
      extracellular environment, to study the relationship between blocking protein
      sulfhydryl groups and Na(+)-K+ pump current (i.p.). In guinea pig ventricular
      myocytes voltage clamped at -30 mV, extracellular pCMPSA (50, 100, and 400
      microM) caused a concentration-dependent reduction in holding current. The
      selective intracellular administration of pCMPSA (100 microM) induced a similar
      inhibition of i.p., albeit over a longer time course. The inhibition of ip
      resulting from either the intracellular or extracellular application of pCMPSA
      (100 microM) was reversed, in part, by the extracellular application of
      dithiothreitol (3 mM). An intracellular oxidant stress was also imposed by using
      diethyl maleate to deplete the intracellular nonprotein sulfhydryl content
      [represented by reduced glutathione (GSH)]. In myocytes isolated from diethyl
      maleate-treated guinea pigs *860 mg/kg i.p., 30 min before study), intracellular
      GSH was depleted by 93% and i.p. was depressed by 38% at all membrane potentials
      tested. We propose that Na(+)-K+ pump function may be related to protein and
      nonprotein sulfhydryl status. Protein sulfhydryl oxidation and glutathione
      depletion may account, in part, for a depression in Na(+)-K+ pump activity during
      reperfusion-induced oxidant stress.

PMID- 7631861
TI  - ATP raises [Ca2+]i via different P2-receptor subtypes in freshly isolated and
      cultured aortic myocytes.
AB  - In vascular smooth muscle, extracellular ATP induces an increase in intracellular
      [Ca2+] ([Ca2+]i). Various agonists have been used to characterize P2-purinoceptor
      subtypes involved in the ATP-induced [Ca2+]i rise, measured by indo 1
      fluorescence, in both freshly isolated and cultured rat aortic smooth muscle
      cells. alpha, beta-Methylene-ATP increased [Ca2+]i via Ca2+ entry through P2x
      receptor channels in freshly isolated but not in cultured cells. 2-Methylthio-ATP
      and ADP failed to release Ca2+ via P2y-receptor activation in freshly isolated
      cells, whereas such a response was obtained in cultured cells. UTP, by
      stimulating P2u receptors, released Ca2+ from intracellular stores in both
      freshly isolated and cultured cells. These results suggest that, in the course of
      the culture process, P2x-receptor activation-induced responses were lost, whereas
      P2y-receptor activation-induced [Ca2+]i rise appeared, these two phenomena being
      independent. Responses to P2x-receptor agonist were lost in all culture
      conditions, whereas functional P2y receptors appeared only in cells that were
      stimulated with serum to induce cell cycle progression. The phenotypic modulation
      of vascular myocytes was therefore associated with a change in the functional P2
      purinoceptor subtypes.

PMID- 7631862
TI  - Effect of acidosis on hydrogen peroxide injury to the isolated perfused rat
      heart.
AB  - We observed that both low and high doses of H2O2 (100 microM and 1 mM,
      respectively) caused significant and irreversible injury to cardiac contractile
      function in the isolated perfused heart model. Using 31P-nuclear magnetic
      resonance spectroscopy, we observed marked metabolic changes following exposure
      to H2O2, especially at the 1 mM dose. Most remarkable were the increases in the
      intensity of the phosphomonoester resonance that occurred immediately after
      exposure to H2O2. The major phosphomonoester species accumulating in hearts
      exposed to 1 mM H2O2 appears to be AMP. Exposure of hearts to H2O2 in the setting
      of metabolic acidosis did not significantly alter the functional response of
      isolated hearts to H2O2. However, the increases in phosphomonoester peak
      intensity following both doses of H2O2 and the decreases in tissue ATP and total
      phosphates following 1 mM H2O2 were attenuated by metabolic acidosis.

PMID- 7631863
TI  - Antihypertensive actions of angiotensin-(1-7) in spontaneously hypertensive rats.
AB  - Observations that angiotensin-(1-7) [ANG-(1-7)] may oppose the vasoconstrictor
      actions of angiotensin II (ANG II) prompted an investigation of the effects of
      the heptapeptide on the maintenance of elevated blood pressure in spontaneously
      hypertensive rats (SHR). ANG-(1-7) (24 micrograms.kg-1.h-1) was infused into the
      jugular vein of 13-wk-old SHR (n = 64), Wistar-Kyoto (WKY, n = 50), and Sprague
      Dawley (SD, n = 18) rats for 2 wk, with the use of osmotic minipumps. Blood
      pressure, fluid and electrolyte balance, plasma vasopressin, and urinary
      excretion of prostaglandin E2 and 6-ketoprostaglandin F1 alpha (6-keto-PGF1
      alpha) were measured at days 2, 7, and 12 of the infusion. In SHR, ANG-(1-7)
      caused a sustained and significant reduction in plasma vasopressin concentration
      that was associated with an increase in urinary prostaglandin E2 and 6-keto-PGF1
      alpha excretion at day 2 after the commencement of the infusion. These changes
      were accompanied by diuresis and natriuresis during the first 3 days of infusion
      in SHR but not in WKY or SD rats. Direct measurements of arterial pressure
      confirmed the lowering effect of ANG-(1-7) on systolic pressure of SHR on day 2
      of treatment with a restoration of the pressure by days 7 and 12. These findings,
      along with our previous demonstration that ANG-(1-7) is an active depressor
      peptide in the intact animal, suggest that ANG-(1-7) may play a significant role
      as a vasodepressor system opposing the hemodynamic actions of ANG II in this
      genetic form of experimental hypertension.

PMID- 7631864
TI  - Enhanced postischemic myocardial recovery following exercise induction of HSP 72.
AB  - The inducible isoform of the 70-kDa heat shock protein (HSP) family, HSP 72, has
      been shown to protect cells from protein-damaging stressors and has been
      associated with myocardial protection. Because exercise is capable of increasing
      HSP 72 content, we determined whether exercise induction of HSP 72 also provided
      myocardial protection. Twenty-eight rats (n = 7 per group) were divided into
      control, heat-shocked (15 min at 42 degrees C), and two exercised groups.
      Exercise consisted of either one or three bouts (on 3 consecutive days) of
      treadmill running for 60 min at 30 m/min. Twenty-four hours after heat shock or
      exercise, hearts were placed on a Langendorff apparatus and subjected to 30 min
      of global ischemia followed by 30 min of reperfusion. Left ventricular developed
      pressure (LVDP), maximal rate of contraction and relaxation (+/- dP/dt,
      respectively), coronary flow, catalase activity, and HSP 72 content were
      determined. During reperfusion, hearts from heat-shocked animals and animals
      subjected to three bouts of exercise recovered a greater percentage of
      preischemic LVDP and +/- dP/dt compared with controls or animals that exercised
      only once. Compared with hearts from controls, HSP 72 content was significantly
      elevated in the hearts of heat-shocked animals and in animals subjected to three
      bouts of exercise, but not in animals that exercised only once. These results
      suggest that exercise induction of HSP 72 can confer an enhanced postischemic
      recovery and may explain, at least in part, the myocardial protection associated
      with exercise.

PMID- 7631865
TI  - Role of natriuretic peptide clearance receptor in in vivo control of C-type
      natriuretic peptide.
AB  - C-type natriuretic peptide (CNP) is a newly described 22-amino acid peptide of
      endothelial cell origin, which has selective cardiovascular actions and is
      structurally related to atrial natriuretic peptide (ANP). Recent in vitro studies
      have demonstrated that an important regulatory pathway for the clearance of
      natriuretic peptides involves binding to a common clearance receptor [natriuretic
      peptide C receptor (NPR-C)]. Although CNP has also been identified as a ligand
      for NPR-C in binding assays, no studies have defined the in vivo interaction of
      CNP with NPR-C. CNP (10 ng.kg-1.min-1) followed by C-ANP-(4-23), a specific
      ligand for NPR-C blockade, was infused intravenously in two groups (both n = 7)
      of anesthetized dogs at two different doses (0.1 or 1.0 micrograms.kg-1.min-1) to
      permit calculation of total metabolic clearance rate (TMCR). C-ANP-(4-23)
      increased circulating CNP and reduced TMCR in both groups. Pulmonary metabolic
      clearance rate was negative at baseline, suggesting a net secretion of CNP across
      the lung, which was increased during CNP infusion and was abolished with NPR-C
      blockade. Renal and femoral metabolic clearance rates were positive at baseline
      and increased with CNP infusion. A decrease in cardiac output and cardiac filling
      pressures in response to CNP administration was potentiated by NPR-C blockade. We
      conclude that 1) circulating CNP achieved by CNP infusion is regulated by NPR-C
      in vivo, 2) the pulmonary circulation is a possible site of CNP secretion, 3) the
      renal and peripheral circulations are sites of CNP clearance, and 4) NPR-C
      blockade potentiates the selective cardiovascular actions of CNP.

PMID- 7631866
TI  - Cardiac staircase and NMR-determined intracellular sodium in beating rat hearts.
AB  - Isolated, perfused rat hearts (30 degrees C, n = 13) were paced from 218 +/- 4
      beats/min to 433 +/- 4 beats/min while systolic and diastolic pressure were
      recorded and intracellular Na+ concentration ([Na+]i) was monitored by 23Na
      nuclear magnetic resonance (NMR) spectroscopy. [Na+]i increased progressively
      with increasing stimulation frequency. In seven hearts (group I) an initial,
      progressive increase in systolic pressure was observed followed by a decrease in
      pressure with further increase in frequency. From the onset, a progressive
      decrease in systolic pressure was observed in group II (n = 6) in response to
      increased frequency. In group I an [Na+]i increase of up to 134 +/- 7% of control
      (P < 0.001) was observed, whereas in group II the gain in [Na+]i with increasing
      pacing rate was attenuated, reaching a maximum of 120 +/- 3% of control (P <
      0.02). The differential pressure response between group I and group II hearts may
      reflect an enhanced sensitivity of rat hearts to the shortening of the
      restitution period of the sarcoplasmic reticulum, outweighing the positive
      inotropic effect induced by an increased [Na+]i. Only in rat hearts whose [Na+]i
      induced increase in pressure outweights the restitution deficit would a complete
      positive inotropic effect be anticipated.

PMID- 7631867
TI  - Regulation of membrane potential and diameter by voltage-dependent K+ channels in
      rabbit myogenic cerebral arteries.
AB  - The hypothesis that voltage-dependent K+ channels are involved in the regulation
      of arterial smooth muscle membrane potential and blood vessel diameter was tested
      by examining the effects of inhibitors [4-aminopyridine (4-AP) and 3,4
      diaminopyridine (3,4-DAP)] of voltage-dependent K+ channels on the membrane
      potential and diameter of pressurized small (100- to 300-microns diam) cerebral
      arteries from rabbit. In response to graded elevations in transmural pressure (20
      100 mmHg), the membrane potential of smooth muscle cells in these arteries
      depolarized and the arteries constricted. 4-AP (1 mM) and 3,4-DAP (1 mM)
      depolarized cerebral arteries by 19 and 21 mV, respectively, when they were
      subjected to a transmural pressure of 80 mmHg. 3-Aminopyridine (3-AP, 1 mM),
      which is a relatively poor inhibitor of voltage-dependent K+ channels,
      depolarized smooth muscle cells in the arteries by 1 mV. 4-AP and 3,4-DAP
      constricted pressurized (to 80 mmHg) cerebral arteries. 3-AP had little effect on
      arterial diameter. 4-AP increased the arterial constriction to transmural
      pressure over a wide range of pressures (40-90 mmHg). The effects of 4-AP and 3,4
      DAP on membrane potential and diameter were not prevented by inhibitors of
      calcium channels, calcium-activated K+ channels, ATP-sensitive K+ channels,
      inward rectifier K+ channels, blockers of adrenergic, serotonergic, muscarinic,
      and histaminergic receptors, or removal of the endothelium. These results suggest
      that voltage-dependent K+ channels are involved in the regulation of membrane
      potential and response of small cerebral arteries to changes in intravascular
      pressure.

PMID- 7631868
TI  - Regulation of PDGF-A: a possible mechanism for angiotensin II-induced vascular
      growth.
AB  - This study was designed to determine the effects of angiotensin II infusion on
      structure of conduit and resistance arteries and to see if the effects correlate
      with changes in platelet-derived growth factor A chain (PDGF-A) gene and protein
      expression. Wistar rats were subcutaneously infused by osmotic minipump with
      either angiotensin II (ANG II) at 200 ng.kg-1.min-1 or physiological saline
      (control) for 14 days. Tail-cuff systolic blood pressure was significantly higher
      in ANG II compared with control rats beginning the second day of infusion and
      continuing to the end of 2 wk. Both aorta and external spermatic artery (first
      order arteriole of the cremaster muscle) developed increased wall-to-lumen ratios
      in the ANG II rats, but this occurred by hypertrophy of the wall in the aorta and
      reduction of the lumen in the arteriole. Digoxigenin-labeled cRNA probes were
      used for in situ hybridization of vascular sections to identify PDGF-A mRNA. Gene
      expression of PDGF-A in ANG II rats was upregulated in the hypertrophied aorta
      and the nonhypertrophied arteriole. With the use of immunocytochemistry
      techniques, PDGF-A and proliferating cell nuclear antigen were increased in the
      aorta but not in the arterioles of ANG II rats compared with control rats. These
      results suggest that the difference in growth response between the aorta and the
      arteriole induced by ANG II may lie in posttranscriptional modification of PDGF-A
      mRNA, differential control of transition, or turnover of PDGF-A protein.

PMID- 7631869
TI  - Physiological relevance of T-tube model parameters with emphasis on arterial
      compliances.
AB  - The T-tube model of systemic arterial circulation was examined with respect to
      the physiological relevance of model parameters. root aortic pressure [Pao(t)]
      and flow [Qao(t)] and descending aortic flow [Qb(t)] were measured in
      anesthetized, open-chest dogs under control conditions, during inflation of a
      balloon positioned in the left external iliac artery (n = 5), and during infusion
      of vasoactive drugs nitroprusside (NTP, n = 4) and phenylephrine (PHL, n = 5).
      With Pao(t) as the input, the model accurately predicted both Qao(t) and Qb(t)
      under all conditions (r2 > 0.96). The balloon inflation data established the
      ability of the model to discriminate between proximal and distal arterial
      mechanical properties. Furthermore, proximal properties (i.e., tube
      characteristic impedances and transit times) were independent of distal
      properties such as terminal compliances and resistances (or equivalently, wave
      reflections). The effects of NTP and PHL were pharmacologically consistent and
      served to further validate this model. NTP primarily affected distal (load)
      properties, whereas PHL altered both load and tube parameters. Physiological
      interpretation of model parameters, particularly compliance, is also discussed.
      The ability of the model to correctly discriminate between proximal and distal
      arterial properties is relevant because these properties may affect
      cardiovascular function differently.

PMID- 7631870
TI  - Alteration of testicular microvascular pressures during venous pressure
      elevation.
AB  - We have addressed the hypothesis that varicocele-related infertility is caused in
      part by a pressure-induced disturbance of testicular convective transport that
      upsets the testicular hormonal environment and thus impairs spermatogenesis. The
      left testis of the hamster [pentobarbital sodium (Nembutal), 70 mg/kg ip] was
      prepared for microcirculatory observations. Testicular venous pressure was
      acutely elevated by ligating collateral routes of venous outflow and partially
      occluding, via a snare, the main venous outflow distal to the pampiniform plexus.
      Simultaneous direct pressure measurements (servo-null method) were made to
      monitor venous pressure elevation and quantify resulting pressure and diameter
      changes in the arterial feed to the testis and in postcapillary venules. The data
      show that over 90% of the venous pressure elevation (VPE) was transmitted to the
      postcapillary venules. VPE affected intravascular pressures throughout the testis
      microvasculature; on average, capsular artery pressure increased by 83% of the
      VPE, although part of this increase was due to a rise in systemic arterial
      pressure. Vasoconstriction helped to buffer the pressure rise in the capsular
      artery, probably at the expense of flow amplitude. Yet the vasoconstriction was
      ineffective in preventing a rise in exchange vessel pressure. These data suggest
      that microvascular fluid exchange may be dramatically altered in varicocele,
      upsetting the hormonal and paracrine environment of the testis, and hence,
      impairing physiological regulation of gametogenesis.

PMID- 7631871
TI  - Alterations in systemic arterial mechanical properties during septic shock: role
      of fluid resuscitation.
AB  - The effects of septic shock (endotoxin; EDTX) on arterial mechanical properties
      were studied in anesthetized rabbits, both in the absence (EDTX alone) and
      presence (EDTX + fluids) of fluid resuscitation. Aortic pressure-flow (n = 20)
      and pressure-diameter (n = 10) measurements were used to calculate systemic
      arterial and regional aortic mechanical properties. At 3 h of EDTX shock, EDTX
      alone rabbits had elevated total peripheral resistance (TPR, + 30%, P < 0.05),
      reduced cardiac output (CO, -40%, P < 0.05), and increased aortic characteristic
      impedance (Zc, +78%, P < 0.05). In contrast, the EDTX + fluids group responded
      with decreased TPR (-30%, P < 0.05), a tendency to increase CO (+23%), and
      elevated Zc (+46%, P < 0.05). A reduction in aortic diameter (-20%, P < 0.05) and
      an increase in elastic modulus (+50%, P < 0.05) and water content (+23%, P <
      0.02) of the aortic wall were observed following endotoxemia. Thus following EDTX
      1) "hyperdynamic" septic shock profile (i.e., low TPR, high CO) was observed only
      when concomitant fluid replacement was provided, 2) aortic wall stiffening was
      present due to both increased smooth muscle tone and vessel wall edema, and 3)
      fluid resuscitation resulted in discordant changes in TPR and Zc, suggesting
      differential flow-induced vasodilation between arteriolar and aortic smooth
      muscle.

PMID- 7631872
TI  - Time- and voltage-dependent modulation of a Kv1.4 channel by a beta-subunit (Kv
      beta 3) cloned from ferret ventricle.
AB  - In mammals, voltage-gated K+ channels can be made of complexes containing alpha
      subunits similar to the Shaker K+ channel and smaller cytoplasmic beta-subunits.
      Recent studies have suggested that these ancillary beta-subunits can modulate K+
      channel gating properties. We studied the effects of a K+ channel beta-subunit,
      Kv beta 3, coexpressed with a Kv1.4 alpha-subunit, FK1, on the time and voltage
      dependence of channel activation, inactivation, recovery from inactivation, and
      deactivation, using an oocyte expression system. Kv beta 3 was found to
      accelerate both the fast and the slow component of Kv1.4 inactivation. Kv beta 3
      also altered the relative contributions of the two components of inactivation by
      increasing the contribution of the slow component to the inactivation process. Kv
      beta 3 slowed recovery from inactivation for Kv1.4, but not for a Kv1.4 deletion
      mutant lacking N-type inactivation. Finally, steady-state activation and the time
      course of Kv1.4 current activation were not strongly influenced by Kv beta 3;
      however, deactivation was slowed in the presence of Kv beta 3. This study
      suggests that Kv beta 3 alters channel states which follow activation.

PMID- 7631873
TI  - Participation of hypothalamic paraventricular nucleus in locus ceruleus-induced
      baroreflex suppression in rats.
AB  - We evaluated the potential role of the paraventricular nucleus (PVN) of the
      hypothalamus in the suppression of baroreceptor reflex (BRR) response by locus
      ceruleus (LC), using adult male Sprague-Dawley rats anesthetized with
      pentobarbital sodium. Electrical stimulation of histologically verified sites in
      the LC elicited significant reduction in the BRR response. This suppressive
      effect of LC on BRR response was appreciably antagonized by bilateral
      electrolytic lesions of the PVN and reversibly blocked by bilateral
      microinjection of 2% lidocaine into similar hypothalamic loci. Local
      administration of the alpha 1-adrenoceptor antagonist, prazosin (50 pmol), or an
      antiserum directed against neuropeptide Y (NPY) (1:20) into the bilateral PVN
      also significantly attenuated the suppression elicited by LC on BRR response. In
      contrast, treatments with the alpha 2-adrenoceptor blocker, yohimbine (50 pmol),
      heat-inactivated NPY antiserum (1:20), artificial cerebrospinal fluid, or normal
      rabbit serum (1:20) produced no discernible effect. These results suggest that
      the PVN may constitute part of the efferent pathways through which LC elicits its
      inhibition on the BRR response. Furthermore, LC may activate this pathway via
      alpha 1-adrenoceptors and NPY receptors in the PVN.

PMID- 7631874
TI  - Postural vascular response vs. sympathetic vasoconstriction in human skin during
      orthostasis.
AB  - Sympathetic activation and local vascular smooth muscle reactions to vessel
      distension contribute to the increase in vascular resistance in the skin during
      orthostasis. The relative contribution of these two mechanisms to the changes of
      skin blood flow along the body axis on standing was investigated in healthy male
      subjects by laser-Doppler (LD) fluxmetry. Compared with recumbency, LD flux (LDF)
      in the standing subjects was reduced by -19.6 +/- 7.2% at the forehead and by 
      69.6 +/- 9.6% in the leg. In the absence of hydrostatic pressure changes, the LDF
      changes on standing averaged -29 +/- 13%, independent of skin region, reflecting
      the effect of vasoconstriction due to sympathetic activation. The postural
      vascular response, elicited by lowering the arm or the leg from heart level, was
      significantly attenuated in orthostasis compared with recumbency. The vessel
      reaction to local alteration of transmural pressure was studied in the skin of
      the forehead and lower leg by application of external pressure in supine
      subjects. No difference in vessel responsiveness to changes of transmural
      pressure was found between these skin sites. The findings suggest that the
      changes of skin perfusion in orthostasis result from a nonadditive interaction of
      height-dependent and -independent mechanisms.

PMID- 7631875
TI  - Hemodynamic basis of oscillations in systemic arterial pressure in conscious
      rats.
AB  - In conscious resting rats, beat-to-beat fluctuations in systemic mean arterial
      pressure (MAP) were compared with those in cardiac output and those in blood flow
      in the renal, mesenteric, and hindquarter vascular beds. Spontaneous oscillations
      (lability) in MAP were observed in frequency bands centered about 1.6 Hz (high:
      HF), 0.4 Hz (mid: MF), and 0.13 Hz (low: LF). Lability of MAP was confined within
      the LF (approximately 8 s) band. Lability of cardiac output, on the other hand,
      showed primary HF oscillations. LF oscillations in regional blood flow were most
      prominent in the mesenteric and renal vascular beds. In these beds, LF
      oscillations in blood flow showed negative phase angles with MAP, whereas those
      between MAP and hindquarter blood flow were positive. Cross correlation analysis
      indicated that approximately 2 s following a LF change in MAP, LF changes in
      mesenteric and renal blood flow occurred opposite to those of MAP. Changes in
      hindquarter flow were negatively correlated with those in MAP about zero time
      delay. Admittance gains were > or = 1 across all frequencies for all vascular
      beds, indicating the absence of autoregulation. This hemodynamic pattern suggests
      that myogenic mechanisms predominantly control mesenteric and renal blood flow in
      a nonautoregulatory but rather superregulatory manner, while autonomic mechanisms
      regulate hindquarter blood flow. Thus, in conscious resting rats, spontaneous
      fluctuations in systemic arterial pressure predominantly exhibit slow
      (approximately 8 s) oscillations, which do not arise from fluctuations in cardiac
      output, but originate from regionally specific myogenic oscillatory mechanisms
      contributing to resistance to flow.

PMID- 7631876
TI  - High correlation of fractals for regional blood flows among resting and
      exercising skeletal muscles.
AB  - The regional blood flow distributions within single skeletal muscles are markedly
      uneven both at rest and during exercise hyperemia. Fractals adequately describe
      this perfusion heterogeneity in the resting lateral head of the gastrocnemius
      muscle as well as in the myocardium. Recently, we provided evidence that the
      fractal dimension for the blood flow distributions in this resting muscle was
      strongly correlated with that of the myocardium in the same rabbit. Prompted by
      this hitherto unknown observation, we have now examined 1) whether fractals also
      describe perfusion distributions within muscles with a varying metabolic
      activity, and 2) whether the fractal dimensions for blood flow distributions to
      these muscles were correlated. We used pentobarbital-anesthetized rabbits and
      cats. The regional distributions of blood flow within various skeletal muscles
      were estimated by microsphere trapping. The data unequivocally showed that the
      perfusion distributions could be described with fractals both in resting and in
      exercising muscle in both species, the corresponding fractal dimensions ranging
      from 1.36 to 1.41. The fractal dimensions were markedly correlated (r2 ranged
      from 0.82 to 0.88) when both various resting and resting plus exercising muscles
      were compared in the same animal. This surprising finding of high correlations
      for the fractal dimensions among various muscles within one animal provides a
      novel characteristic of blood flow heterogeneity.

PMID- 7631877
TI  - Preconditioning reduces infarct size but accelerates time to ventricular
      fibrillation in ischemic pig heart.
AB  - Preconditioning protects the rat heart from ventricular arrhythmias. However, the
      mechanism of this beneficial effect and its existence in large animal models
      remain unknown. We submitted 49 pigs to 40 min of left anterior descending
      coronary occlusion and 2 h of reperfusion and assessed the incidence of
      ventricular fibrillation (VF) and time to VF. Monophasic action potential
      duration (MAPD) and ventricular fibrillation threshold (VFT) were measured
      throughout the experiment. Preconditioning significantly reduced infarct size but
      failed to reduce the incidence of VF either during the 40-min ischemic insult or
      the following reperfusion. Moreover, preconditioning accelerated the onset of VF
      during the prolonged ischemia; time to VF averaged 8 +/- 2 min in the
      preconditioned group vs. 18 +/- 2 min in the control group (P < 0.05). This
      premature peak of VF in preconditioned hearts was associated with a significant
      decrease of VFT and shortening of MAPD. This suggests that preconditioning does
      not limit the incidence of VF in the pig model. Rather, preconditioning decreases
      the time to VF in this species, likely through lowering of the VFT and shortening
      of the action potential duration.

PMID- 7631879
TI  - Morphometry and muscle gene expression in hypertrophied hearts from polyomavirus
      large T antigen transgenic mice.
AB  - Transgenic mice expressing polyomavirus large T antigen (PVLT) in cardiomyocytes
      develop a cardiac hypertrophy in adulthood. Morphometric analysis identified
      cardiomyocytes enlarged up to ninefold in cross-sectional area in the adult
      transgenic hearts compared with normal age-matched nontransgenic hearts. Most
      enlarged cardiomyocytes were found in the subendocardium, whereas normal-sized
      cardiomyocytes were localized to the midmyocardium. Transgenic hearts did not
      express detectable skeletal muscle actin mRNA or protein, or skeletal troponin I
      isoform mRNA. Some, but not all, transgenic hearts expressed an increase in the
      beta-myosin heavy chain mRNA. All five transgenic mice tested had increased
      expression of atrial natriuretic factor (ANF) mRNA. Whereas normal hearts
      expressed three myosin light chain proteins of 19, 16, and 15 kDa, we found that
      the 19-kDa myosin light chain was not observed in the transgenic hearts. We
      conclude that adult, PVLT-expressing, transgenic mice developed enlarged
      cardiomyocytes with an increase in beta-myosin heavy chain and ANF mRNA
      expression, but a widespread skeletal isoform usage was not present in these
      transgenic mice. The adult transgenic hearts thus display histological and
      molecular changes similar to those found in hypertrophy induced by a pressure
      overload in vivo.

PMID- 7631878
TI  - Paraventricular nucleus histamine increases blood pressure by adrenoreceptor
      stimulation of vasopressin release.
AB  - The role of adrenoreceptor stimulation and the peripheral mechanism mediating the
      increase in mean arterial blood pressure (MAP) and heart rate (HR) during
      administration of histamine (HA) in the paraventricular nucleus/anterior
      hypothalamus (PVN/AH) was evaluated in conscious rats. HA administered through
      microdialysis probes in the PVN/AH region increased MAP (18 +/- 1 mmHg) and HR
      (81 +/- 10 beats/min). The pressor response was abolished by simultaneous
      administration of phentolamine (alpha 1- and alpha 2-antagonist) or prazosin
      (alpha 1-antagonist) but not altered by yohimbine (alpha 2-antagonist). The
      tachycardia was not effected by any adrenergic antagonist. Furthermore,
      ganglionic blockade did not reduce the increase in MAP (21 +/- 2 mmHg) during
      PVN/AH perfusion with HA, while V1-vasopressin receptor blockade abolished the
      pressor response (4 +/- 2 mmHg). These data suggest that HA administered to the
      PVN/AH increases blood pressure by local release of norepinephrine and alpha 1
      adrenoreceptor stimulation of vasopressin secretion, while the tachycardia is not
      mediated by alpha-adrenoreceptors.

PMID- 7631880
TI  - Differential effect of 5- and 15-lipoxygenase products on ischemically sensitive
      abdominal visceral afferents.
AB  - The effects of 5- and 15-lipoxygenase products, leukotriene B4 (LTB4) and
      (8R,15S)-dihydroxyeicosa(5E-9,11,13Z)tetraenoic acid (8R,15S-diHETE), on
      ischemically sensitive abdominal visceral C fiber afferents were evaluated,
      because this system is important in sensitizing cutaneous afferents. Single-unit
      activity of abdominal visceral C fiber afferents was recorded from the right
      thoracic sympathetic chain of anesthetized cats during 5 min of ischemia.
      Inhibition of 5-lipoxygenase with WY-50295 tromethamine (5 mg/kg iv) augmented
      the impulse activity from 0.48 +/- 0.15 to 0.79 +/- 0.24 impulses/s (P < 0.05) in
      seven ischemically sensitive afferents. Conversely, topical application of LTB4
      (125 ng) directly onto the receptive field attenuated impulse activity of 10
      ischemically sensitive C fiber afferents from 0.82 +/- 0.23 to 0.42 +/- 0.10
      impulses/s (P < 0.05). In additional cats, application of 8R,15S-diHETE (125 ng)
      onto the receptive field augmented the impulse activity of nine ischemically
      sensitive C fiber afferents (from 0.48 +/- 0.15 to 0.70 +/- 0.15 impulses/s, P <
      0.05) and significantly decreased the mechanical threshold of these nine
      afferents, whereas application of 8S,15S-diHETE (125 ng), a stereoisomer of
      8R,15S-diHETE, attenuated the impulse activity from 0.77 +/- 0.48 to 0.45 +/-
      0.13 impulses/s (P < 0.05) in six additional ischemically sensitive C fiber
      afferents. In animals pretreated with aspirin (50 mg/kg iv, n = 6) or 8S,15S
      diHETE (125 ng, n = 6), WY-50295 tromethamine (5 mg/kg iv) still potentiated the
      impulse activity of ischemically sensitive C fiber afferents. These data indicate
      that 8R,15S-diHETE interacts with stereospecific receptors to sensitize, whereas
      LTB4 reduces, the response of abdominal visceral afferents to ischemia.
      Furthermore the data suggest that the augmented response of afferents to
      abdominal ischemia after inhibition of 5-lipoxygenase is, at least in part,
      independent of shunting to the cyclooxygenase or 15-lipoxygenase system.

PMID- 7631881
TI  - Serotonin enhances gastric acid response to TRH analogue in dorsal vagal complex
      through 5-HT2 receptors in rats.
AB  - The effect of serotonin (5-HT) and thyrotropin-releasing hormone (TRH) analogue,
      p-Glu-His-[3,3'-dimethyl]-Pro-NH2 (RX-77368), injected into the dorsal vagal
      complex (DVC) on gastric acid secretion was assessed in urethan-anesthetized rats
      with gastric cannula. 5-HT (0.1, 0.2, 1, or 10 nmol into the DVC) enhanced the
      acid response to RX-77368 (25 pmol, DVC) by 54, 100, 147, and 144%, respectively,
      whereas 5-HT given alone had no effect. The 5-HT2 receptor agonists (1 nmol,
      DVC), ( +/- )-1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane hydrochloride, 1
      (alpha, alpha, alpha-trifluoro-m-tolyl)-piperazine hydrochloride, and alpha
      methyl-5-HT increased the gastric acid response to coinjection of RX-77368 (25
      pmol) by 153, 108, and 96%, respectively, whereas 8-hydroxy-2-(di-n
      propylamino)tetralin (5-HT1A), 7-trifluoromethyl-4(4-methyl-1-piperazinyl)-
      pyrrolo[1,2-a]quinoxaline (5-HT1A/1B), and 3-(2-aminoethyl)-2-methyl-1-H-indol-5
      ol hydrochloride hydrate (2-methyl-5-HT3) did not. The 5-HT2 receptor antagonist,
      3-[2-(4-fluorobenzoyl)-1-piperdinyl]ethyl]-2,4(1H,3H)-quinazoli nedone tartrate
      (ketanserin; 20 nmol), injected intracisternally abolished the potentiating
      action of 5-HT injected into the DVC with RX-77368, whereas the 5-HT antagonists
      8-[4-(4-fluorophenyl)-4-oxobutyl]-1-phenyl-1,3,8-triazaspiro[4,5]- decan-4-one
      (spiperone; 5-HT2/1A) and 1,2,3,9-tetrahydro-9-methyl-3-[(2-methyl-1H-imidazol-1-
      yl)methyl]-4H-carbazol-4-one hydrochloride dihydrate (ondansetron; 5-HT3) did
      not. Ketanserin (1 nmol/site bilaterally into the DVC) decreased the acid
      response to kainic acid injected into the raphe pallidus by 62%. These data
      suggest that 5-HT acting at 5-HT2 receptors in the DVC potentiates the gastric
      acid response to exogenous and endogenous TRH.

PMID- 7631882
TI  - Mechanisms of proximal proton secretion in BBM of herbivorous, omnivorous, and
      carnivorous species.
AB  - The mechanisms of proton secretion by the proximal brush-border membrane (BBM)
      were compared in carnivorous (dog), omnivorous (human, pig, rat), and herbivorous
      (rabbit, hamster) species. The activity of the proton pump (V-type bafilomycin
      sensitive H(+)-adenosinetriphosphatase) and of the Na+/H+ exchanger (amiloride
      sensitive quenching of acridine orange fluorescence), the two major proton
      secretion mechanisms, was measured. The enzymatic activity of the H(+)
      adenosinetriphosphatase activity was measured in intact (endosomes) and
      solubilized (0.1% deoxycholate or Triton X-100) BBM vesicles isolated by
      conventional Mg2+ precipitation techniques. In all species, but not in humans,
      the fraction of the ATP turnover energizing the proton pump (bafilomycin
      sensitive respiration) was also measured in isolated proximal tubules.
      Significant differences in acid transport mechanisms were noted between species,
      with the proton pump predominating in the BBM of carnivorous species and the
      Na+/H+ exchanger predominating in the BBM of herbivorous species. The fraction of
      respiration suppressible by bafilomycin in proximal tubules was also different in
      all the species considered. This may indicate a different organization of
      proximal H+ transport related to the species-specific menace to acid-base
      balance.

PMID- 7631883
TI  - Naloxone attenuates poststimulatory respiratory depression of laryngeal origin in
      the adult cat.
AB  - Poststimulatory depression in respiratory activity induced by superior laryngeal
      nerve (SLN) stimulation was quantitatively investigated in 20 adult cats. The
      role played in this phenomenon by endogenous opioids was studied using the opiate
      antagonist naloxone. The effects of hypercapnia on the same phenomenon were also
      investigated for comparison. Experiments were performed on cats anesthetized with
      pentobarbitone or alpha-chloralose, vagotomized, paralyzed, and artificially
      ventilated with 100% O2. Some animals were also carotid sinus denervated.
      Respiratory output was monitored as integrated phrenic nerve activity. SLN
      stimulation produced apnea, which outlasted the stimulation period; when
      respiration resumed, it was markedly depressed as revealed mainly by a decrease
      in phrenic minute output, respiratory frequency, and rate of rise of inspiratory
      activity. Phrenic output recovered gradually to control levels following an
      exponential time course. These effects varied as a function of the duration of
      SLN stimulation. Naloxone administration (0.8 mg/kg iv) significantly reduced the
      duration of poststimulatory apnea and attenuated the depression of phrenic minute
      output of the first recovery breath as a result of changes in peak phrenic
      activity; it also accelerated the time course of recovery. Hypercapnia did not
      affect the duration of poststimulatory apnea, but attenuated the initial
      poststimulatory depression because of changes in respiratory frequency; the rate
      of recovery was reduced. The results provide characterization of poststimulatory
      respiratory depression of laryngeal origin in the adult cat and suggest a role of
      endogenous opioids in its genesis or modulation.

PMID- 7631884
TI  - Swim training alters sympathoadrenal and endocrine responses to hemorrhage in
      borderline hypertensive rats.
AB  - Swim training alters cardiovascular, sympathoadrenal, and endocrine responses to
      hemorrhage in borderline hypertensive rats (BHR). The effects of 10, 20, and 30%
      blood volume hemorrhages on cardiovascular, sympathoadrenal, and endocrine
      function in swim-trained (T; 2 h/day, 5 day/wk for 10-12 wk) and age-matched,
      untrained, sedentary, control (UT) borderline hypertensive rats (BHR) were
      assessed. Heart rate (HR) in UT BHR was significantly greater during the baseline
      (rest) period than T BHR. HR increased slightly from baseline in both groups
      after 10% hemorrhage but was significantly decreased in both groups after 20 and
      30% hemorrhages. The decrease was eliminated by atropine (1 mg/kg iv). Systolic
      (SBP) and diastolic (DBP) blood pressures decreased significantly after 20 and
      30% hemorrhages in both T and UT BHR but were not different between the groups at
      these times. Plasma norepinephrine levels were significantly increased above
      baseline after 20 and 30% hemorrhages in UT BHR and were significantly greater in
      UT BHR than T BHR after 30% hemorrhage. Plasma glucose levels increased
      significantly after 30% hemorrhage in both groups but were significantly greater
      in UT BHR than T BHR. Both plasma norepinephrine and plasma epinephrine levels
      showed strong positive correlations with plasma glucose. After 20 and 30%
      hemorrhages, plasma insulin levels were unchanged in T BHR but were significantly
      decreased in UT BHR. Plasma insulin levels were significantly less in UT than T
      BHR after 30% hemorrhage. These results suggest that swim training alters the
      effect that hemorrhage exerts on endocrine and sympathoadrenal function in
      BHR.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7631885
TI  - Hypothalamic sites mediating cardiovascular effects of microinjected bicuculline
      and EAAs in rats.
AB  - Microinjection of gamma-aminobutyric acidA receptor antagonist bicuculline
      methiodide (BMI) into either the dorsomedial hypothalamic nucleus (DMH) or the
      nearby paraventricular hypothalamic nucleus (PVN) has been reported to evoke
      marked tachycardia and modest pressor effects. We compared the effects of
      microinjecting BMI and excitatory amino acids (EAAs) into 1) the DMH, 2) the PVN,
      and 3) an intermediate area between the two nuclei. In conscious rats,
      microinjection of (in pmol) 10 BMI, 0.5 kainic acid, or 5 N-methyl-D-aspartate
      into the DMH markedly increased heart rate and slightly elevated arterial
      pressure, whereas injections into other regions provoked changes that
      progressively declined in magnitude with increasing distance from the nucleus. A
      similar pattern was evident in urethan-anesthetized rats, where the shortest
      latency to onset of BMI-induced increases in heart rate was seen after injection
      into the DMH. These findings demonstrate that the cardiovascular changes seen
      after microinjection of BMI or EAAs into the medial hypothalamus result from an
      action in the DMH and not from spread to the PVN.

PMID- 7631886
TI  - Chronic sodium loading augments natriuretic response to acute volume expansion in
      the preweaned rat.
AB  - Positive sodium balance is necessary for normal somatic growth of the neonate,
      and the neonatal renal response to volume expansion (VE) is attenuated compared
      with the adult. To test the hypothesis that dietary sodium modulates the
      developmental response to VE, preweaned rats were artificially reared with either
      a normal (25 meq/l)- or high-sodium (145 meq/l) diet for 7-8 days and were
      compared with adult rats receiving normal or high sodium. Serum sodium
      concentration remained normal in adults on high sodium, whereas neonates became
      hypernatremic. Glomerular filtration rate (GFR), urinary flow (V), and urinary
      sodium (UNaV) were measured before and after acute saline VE (1% body wt). While
      remaining constant in preweaned rats, GFR increased > 50% in adult rats after VE
      (P < 0.05). High sodium intake augmented V and UNaV after VE but was not
      sustained in neonates as in adults. Plasma atrial natriuretic peptide (ANP) and
      guanosine 3',5'-cyclic monophosphate excretion (UcGMPV) were measured, and
      baseline UcGMPV was lower in preweaned rats receiving normal sodium but increased
      to levels similar to adult levels after VE. Postexpansion plasma ANP was higher
      in preweaned rats than in adult rats and was not affected by dietary sodium
      regardless of age. We conclude that the attenuated postexpansion natriuresis in
      the neonate is due in part to an adaptive response to limited sodium intake.
      However, neonatal compensation to increased sodium intake is incomplete and
      independent of plasma ANP.

PMID- 7631887
TI  - Corticosterone regulates behavioral effects of lipopolysaccharide and interleukin
      1 beta in mice.
AB  - The modulatory role of endogenous corticoids in the behavioral effects of
      lipopolysaccharide (LPS) and recombinant human interleukin-1 beta (IL-1 beta) was
      studied in mice. Adrenalectomy enhanced the depression of social exploration
      induced by subcutaneous injection of 200 ng of IL-1 beta or 2 micrograms of LPS.
      This effect was mimicked by an acute injection of the progesterone antagonist RU
      38486 (0.25-1 mg). Chronic replacement with a 15-mg corticosterone pellet
      abrogated the enhanced susceptibility of adrenalectomized animals to 200 ng of IL
      1 beta but had only partial protective effects on their response to 400 ng of IL
      1 beta and LPS. These results suggest that the pituitary-adrenal response to
      cytokines exerts an inhibitory feedback on the cell targets that mediate the
      behavioral effects of LPS and IL-1 beta.

PMID- 7631888
TI  - Hypoxemia in the absence of blood loss or significant hypotension causes
      inflammatory cytokine release.
AB  - Although hemorrhagic shock causes a significant elevation of circulating levels
      of proinflammatory cytokines [tumor necrosis factor-alpha (TNF-alpha),
      interleukin (IL)-1 beta, IL-6], it remains unknown whether hypoxemia per se in
      the absence of blood loss activates macrophages (Mo) to release increased amounts
      of these mediators. To study this, hypoxemia was induced in C3H/HeN mice by
      placing them in a plastic box that was flushed with a gas mixture containing 95%
      N2-5% O2 for 60 min, followed by return of the mice to room air. For control
      animals, the plastic box was flushed with room air. At 0, 2, or 24 h thereafter,
      blood samples were obtained, plasma was separated, and then peritoneal Mo (pMo)
      and Kupffer cells (KC) were isolated and incubated at 37 degrees C for 24 h with
      lipopolysaccharide. The Mo supernatants, as well as plasma samples, were assayed
      for TNF-alpha, IL-1 beta, and IL-6 with the use of specific bioassays. Hypoxemia
      induced a significant (P < 0.05) increase in plasma TNF-alpha levels during the
      entire study period while circulating IL-6 was elevated by 313% (P < 0.01) at 24
      h after hypoxemia compared with shams. Moreover, the release of TNF-alpha, IL-1
      beta, and IL-6 by pMo and KC was markedly increased after hypoxemia compared with
      shams. Thus, hypoxemia in itself, in the absence of any blood loss or tissue
      injury, induces release of proinflammatory cytokines, which may contribute to
      systemic inflammation following hypoxemia.

PMID- 7631889
TI  - Intracisternal rat pancreatic polypeptide stimulates gastric emptying in the rat.
AB  - Pancreatic polypeptide (PP) has been shown to alter gastrointestinal functions,
      including increased gastric acid secretion and motility following brain stem
      injections of PP. The present study investigated the effect of an intracisternal
      injection of PP on the rate of gastric emptying. Additionally, the efficacy of
      the rat and bovine forms of the peptide was compared. Rats anesthetized with
      ether received an intracisternal injection of rat PP, bovine PP, or vehicle and,
      upon regaining consciousness, were fed a liquid test "meal." Intracisternal rat
      PP produced a marked enhancement in gastric emptying compared with control
      animals. Bovine PP, at doses equimolar to or three times greater than the
      effective rat PP dose, produced no change in gastric emptying. Pretreatment with
      systemic atropine prior to central injection of rat PP eliminated the stimulation
      of emptying, suggesting that PP acts through a cholinergic mechanism. When
      equimolar doses of rat or bovine PP were microinjected directly into the dorsal
      vagal complex, the region containing PP receptors, both were capable of
      stimulating antral motility. The response to bovine PP, however, was delayed and
      reduced compared with that seen following rat PP. The results suggest that rat PP
      strongly stimulates gastric emptying in rats and that bovine PP, depending on the
      route of administration, is either ineffectual or a weaker agonist for central PP
      receptors.

PMID- 7631890
TI  - Suppression of men's responses to seasonal changes in day length by modern
      artificial lighting.
AB  - We recently reported that humans have conserved mechanisms, like those that exist
      in other animals, which detect changes in day length and make corresponding
      adjustments in the duration of nocturnal periods of secretion of melatonin and of
      other functions. We detected these responses in individuals who were exposed to
      artificial "days" of different durations. The purpose of the present study was to
      determine whether men who are exposed to natural and artificial light in an urban
      environment at 39 degrees N are still able to detect and respond to seasonal
      changes in duration of the natural photoperiod. We measured profiles of circadian
      rhythms during 24-h periods of constant darkness (< 1 lx) and found no summer
      winter differences in durations of nocturnal periods of active secretion of
      melatonin, rising levels of cortisol, high levels of thyrotropin, and low levels
      of rectal temperature. The results of this and our previous study suggest that
      modern men's use of artificial light suppresses responses to seasonal changes in
      the natural photoperiod that might otherwise occur at this latitude.

PMID- 7631891
TI  - Voluntary exercise increases gonadotropin secretion in male Golden hamsters.
AB  - To determine the effect of voluntary exercise and food restriction on
      reproductive hormone secretion, 48 adult male hamsters were placed in cages with
      (EX) or without (SED) running wheels. One-half of the animals in each exercise
      group was fed ad libitum, and the other half was food restricted to reduce their
      body weight to 90 g over 4 wk. After 10 wk, the EX ad libitum-fed group had much
      larger testes and much higher serum follicle-stimulating hormone and testosterone
      levels than the other three groups, but these values in the EX food-restricted
      hamsters were similar to those in the SED food-restricted group. In experiment 2,
      20 adult male hamsters were castrated and later implanted with silicone rubber
      capsules containing testosterone. Two weeks after implantation of the capsules,
      the serum follicle-stimulating hormone levels were higher in the EX than in the
      SED group of testosterone-treated hamsters, but not in animals receiving blank
      capsules. These data suggest that exercise increases gonadotropin secretion by
      inhibiting the negative feedback of testosterone.

PMID- 7631893
TI  - Control of renal medullary blood flow by vasopressin V1 and V2 receptors.
AB  - Experiments were performed in anesthetized renal-denervated rats to determine the
      contribution of renal medullary vasopressin V1 and V2 receptor stimulation in the
      regulation of renal medullary blood flow. Renal medullary interstitial infusion
      of the selective V1 agonist [Phe2,Ile3,Orn8]vasopressin (2 ng.kg-1.min-1)
      significantly decreased outer medullary blood flow by 15% and inner medullary
      blood flow by 35%, as measured with implanted optical fibers for laser-Doppler
      flowmetry. Medullary interstitial infusion of equimolar doses of arginine
      vasopressin (AVP) also decreased outer medullary blood flow by 15% but decreased
      inner medullary blood flow by only 17%, a decrease significantly less than that
      during the infusion of the V1 agonist. These results were confirmed in
      videomicroscopy experiments on the exposed papilla, which demonstrated that the
      V1 agonist and AVP decreased descending and ascending vasa recta capillary red
      blood cell velocity and calculated blood flow, with greater decreases during
      infusion of the V1 agonist. In further laser-Doppler flowmetry studies,
      stimulation of V2 receptors by medullary interstitial infusion of 1-desamino-8-D
      arginine vasopressin (2 ng.kg-1.min-1) or AVP in rats pretreated with the
      vasopressin V1 receptor antagonist d(CH2)5[Tyr(Me)2,Ala-NH2]AVP increased renal
      medullary blood flow by 16 +/- 3 and 27 +/- 8%, respectively. The present
      experiments indicate that vasopressin V1 receptor stimulation serves to decrease
      renal medullary blood flow while V2 receptor stimulation appears to increase
      renal medullary blood flow; however, the net effect of AVP is to decrease renal
      medullary blood flow.

PMID- 7631892
TI  - Blood pressure and fluid-electrolyte balance in ANF-transgenic mice on high- and
      low-salt diets.
AB  - Transgenic mice overexpressing an atrial natriuretic factor (ANF) fusion gene
      (TTR-ANF) and their nontransgenic siblings were placed on a high- (8%) or low (<
      0.008%)-salt diet for 14 days to determine whether the lifelong elevation of ANF
      in the transgenic animals compromised their ability to maintain fluid-electrolyte
      balance. Steady-state dietary intake and urinary output of sodium and chloride
      were not statistically different between TTR-ANF and control groups on either
      diet. By contrast, water intake and urine volume were markedly elevated in the
      TTR-ANF group on either diet. Arterial blood pressure, measured in anesthetized
      mice at the end of the dietary regimen, was significantly and similarly reduced
      in the TTR-ANF compared with control groups on either diet, although high salt
      intake was associated with increased pressure in both groups. Renal excretion of
      fluid and electrolytes was studied in the anesthetized mice before and after
      acute blood volume expansion. Although the absolute increase in fluid and
      electrolyte excretion was much greater on the high- than on the low-salt diet in
      both groups, TTR-ANF mice had an exaggerated response relative to controls on
      either diet. On the basis of these results, we conclude the following. 1) When
      they are stimulated, renal salt-conserving mechanisms are sufficiently powerful
      to overcome the expected natriuretic effects of chronic elevation of plasma ANF;
      however, the natriuretic potential of ANF can be expressed in the short term when
      the counterregulatory mechanisms are inactivated. 2) ANF exerts a chronic
      hypotensive effect that is independent of changes in renal salt
      excretion.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7631894
TI  - Acclimatization to high altitude increase muscle sympathetic activity both at
      rest and during exercise.
AB  - This investigation examined the relationship between alterations in plasma
      norepinephrine associated with 21 days of high-altitude exposure and muscle
      sympathetic activity both at rest and during exercise. Healthy sea level
      residents, divided into a control group (n = 5) receiving a placebo or a drug
      group (n = 6) receiving 240 mg/day of propranolol, were studied while at sea
      level, upon arrival (acute), and after 21 days of residence (chronic) at 4,300 m.
      Arterial norepinephrine levels and net leg uptake and release of norepinephrine
      were determine both at rest and during 45 min of submaximal exercise via samples
      collected from femoral arterial and venous catheters. Arterial norepinephrine
      levels increased significantly after chronic altitude exposure both at rest (84%)
      and during exercise (174%) compared with sea level and acute values. A net uptake
      of norepinephrine was found in resting legs at sea level (0.28 +/- 0.05 nmol/min)
      and with acute exposure (0.07 +/- 0.06 nmol/min); however, a significant switch
      to net leg norepinephrine release was observed with chronic altitude exposure
      (0.51 +/- 0.11 nmol/min). With exercise, a net release of norepinephrine by the
      leg occurred across all conditions with chronic exposure, again eliciting the
      greatest values (5.3 +/- 0.6, 8.0 +/- 1.7, and 14.4 +/- 3.1 nmol/min for sea
      level, acute, and chronic exposure, respectively). It was concluded that muscle
      sympathetic activity is significantly elevated both at rest and during submaximal
      exercise as a result of chronic high-altitude exposure, and muscle is a major
      contributor to the increase in plasma norepinephrine levels associated with
      prolonged altitude exposure. The presence of dense beta-blockade did not alter
      this adaptation to altitude.

PMID- 7631895
TI  - Changes in circadian rhythms of body temperature and sleep in old rats.
AB  - We examined the relationship between circadian rhythms of body temperature (CTR)
      and sleep in adult and old female rats. Body temperature was recorded
      telemetrically for months and sleep for 24 h in a 12:12-h light-dark cycle at 23
      degrees C. Some old rats had robust CTRs (old good), and some had unstable or
      absent CTRs (old unstable). Old unstable rats had lower daily mean body
      temperatures, smaller daily amplitudes, and a more advanced CTR phase than adult
      rats and old good rats. Old good rats matched adult rats in all measures. In old
      good rats, circadian parameters of sleep were normal, whereas in old unstable
      rats the amplitudes of slow-wave and rapid eye movement sleep were decreased,
      although the amounts were equivalent. Rhythmic parameters of sleep correlate well
      with the stability or instability of the CTR, whereas homeostatic regulation of
      rapid eye movement and slow-wave sleep do not seem to be impaired during aging
      and are independent of the stability of the CTR.

PMID- 7631896
TI  - Glossopharyngeal nerve transection does not compromise the specificity of taste
      guided sodium appetite in rats.
AB  - The chorda tympani nerve (CT) has been shown to be critical in the sodium
      specific drinking behavior of sodium-depleted rats, but the role of other
      gustatory nerves and the contribution of the major salivary glands remain to be
      elucidated. In this study, rats received either bilateral section of the CT (CTX)
      or the glossopharyngeal nerve (GLX), extirpation of the sublingual and
      submaxillary salivary glands (DSAL), or sham surgery. After recovery, rats were
      sodium depleted with furosemide and tested for their licking responses to 0.05
      and 0.3 M NaCl, KCl, CaCl2, and NH4Cl, as well as distilled water in an automated
      gustometer. Rats that received GLX maintained a specific sodium appetite
      comparable to controls despite denervation of approximately 64% of the taste
      buds. In contrast, compared with control rats, CTX and DSAL rats had altered
      response profiles, showing much smaller differences in licking to NaCl relative
      to the other stimuli. This was accompanied by a substantially lower lick rate in
      DSAL rats, raising the possibility that general licking impairments contributed
      to the decreased NaCl responsiveness in these rats. These findings imply that the
      CT, but not the glossopharyngeal nerve, is necessary for the maintenance of
      normal sodium-specific, taste-guided behavior under sodium deplete conditions.

PMID- 7631897
TI  - Autonomic nervous system activity in weight gain and weight loss.
AB  - Studies in both animals and humans indicate that the autonomic nervous system
      (ANS) responds to changes in systemic energy balance. In the present study, ANS
      response to weight change was examined by sequential blockade of cardiac
      autonomic innervation with parasympathetic (atropine) and sympathetic (esmolol)
      blockers. Change in heart period (interbeat interval) from baseline after
      atropine defined the amount of parasympathetic control (PC), and the subsequent
      change after esmolol defined the amount of sympathetic control (SC). In nonobese
      subjects, weight gain to 10% above initial body weight resulted in a decrease in
      PC and an increase in SC, and conversely, weight loss to 10% below initial weight
      resulted in an increase in PC and a decrease in SC. In obese subjects, weight
      loss resulted in the same pattern of changes in PC and SC. The major changes were
      in the parasympathetic arm of the ANS. These findings support the hypothesis that
      the ANS acts to oppose weight change.

PMID- 7631898
TI  - Cellular oxygen consumption depends on body mass.
AB  - Hepatocytes were isolated from nine species of mammal of different body mass (and
      standard metabolic rate). The cells were incubated under identical conditions and
      oxygen consumption measured. The rate of oxygen consumption (per unit mass of
      cells) scaled with body mass with exponent -0.18. In general, there was a 5.5
      fold decrease in oxygen consumption rate with a 12,500-fold increase in body
      mass. The decrease in oxygen consumption rate was not due to an increase in cell
      volume with increasing body mass but to a decrease in intrinsic metabolic
      activity of the cells. This novel finding confirms and explains the decrease in
      oxygen consumption rate measured in tissue slices from larger mammals by H. A.
      Krebs (Biochim. Biophys. Acta 4: 249-269, 1950) and recently by P. Couture and A.
      J. Hulbert [Am. J. Physiol. 268 (Regulatory Integrative Comp. Physiol. 37): R641
      R650, 1995].

PMID- 7631899
TI  - TNF soluble receptor and antiserum against TNF enhance lipopolysaccharide fever
      in mice.
AB  - We tested the effects of tumor necrosis factor (TNF) soluble receptor (sTNFR) and
      anti-TNF serum (anti-TNF) administered intraperitoneally on fever induced by
      lipopolysaccharide (LPS) in mice. Both agents have been shown to block
      bioactivity of mouse TNF-alpha. Core temperature (Tb) and locomotor activity in
      unrestrained mice were measured by biotelemetry. Within 1 h from the LPS
      injection (2.5 mg/kg ip) Tb decreased below normal for 5-6 h and motor activity
      was depressed for the following 48 h. After this initial reduction, Tb increased
      and reached a peak at approximately 24 h postinjection. Anti-TNF and sTNFR
      blocked this "hypothermic phase" after LPS, and the fevers started sooner;
      however, the levels and time of peak temperature did not change markedly. In
      addition, a human recombinant TNF-alpha given intraperitoneally abolished fever
      and prolonged the fall of Tb in mice after LPS. We conclude that the reduction of
      Tb soon after injection of LPS in mice is dependent on TNF-alpha.

PMID- 7631900
TI  - Determinants of high-fat diet hyperphagia: experimental dissection of orosensory
      and postingestive effects.
AB  - High-fat diets often promote greater caloric intake and/or weight gain than high
      carbohydrate diets in both laboratory animals and humans. Because altering the
      fat content of a diet simultaneously changes both its sensory properties and
      postingestive effects, it is unclear whether high-fat hyperphagia is due to the
      diet's palatability, its postingestive effects, or both. The present studies
      isolated the independent capacity of the orosensory and postingestive effects of
      a liquid high-fat diet (High-Fat) to produce overeating relative to an isocaloric
      liquid high-carbohydrate (High-CHO) diet. Rats fed High-Fat orally ate more
      calories and gained more weight over 16 days than rats fed High-CHO orally. One
      bottle sham-feeding intake of High-Fat and High-CHO did not differ, but in two
      bottle sham-feeding tests High-Fat was clearly preferred. When orosensory
      influences on intake were equated via chronic self-regulated intragastric
      feeding, High-Fat still promoted greater intake than High-CHO, although absolute
      intake across both diets was lower during intragastric feeding relative to oral
      feeding. An analysis of short-term intake revealed that rats accustomed to
      infusion of High-CHO increased meal size immediately when switched to High-Fat.
      The present results, coupled with previous findings, suggest that the
      postingestive effects of fat enhance daily caloric intake in two ways: 1) during
      a meal, fat produces less suppression of intake per calorie than carbohydrate;
      and 2) after a meal, fat produces less suppression of intake per calorie during
      the intermeal interval than carbohydrate.

PMID- 7631902
TI  - Cardiovascular effects of serotonin in the nucleus of the solitary tract.
AB  - The cardiovascular regulatory role of serotonin [5-hydroxytryptamine (5-HT)] in
      the solitary tract nucleus (NTS) was investigated in urethan-anesthetized Wistar
      rats. Unilateral microinjection of 5-HT (5 nmol in 50 nl) into the NTS evoked
      depressions of both arterial pressure (-20 +/- 1 mmHg) and heart rate (-43 +/- 6
      beats/min). Induction of bradycardia and hypotension was repeatable and
      consistently obtained with injections into the NTS but not into neighboring
      structures. Microinjection of the nonselective 5-HT receptor antagonist
      methiothepin or the 5-HT1A/5-HT1B antagonist pindolol prevented any
      cardiovascular change by subsequent microinjection of 5-HT into the NTS. In
      contrast, microinjection of the 5-HT2-selective antagonist ketanserin or the 5
      HT1A antagonist spiroxatrine had no effect on the subsequent effects of 5-HT.
      Bilateral vagal denervation prevented the bradycardia induced by 5-HT, whereas
      the vasodepression remained intact. These data provide evidence that 5-HT in the
      NTS evokes vagal chronotropic cardioinhibition and sympathetic withdrawal and
      suggest that this action is mediated by 5-HT1 serotonergic receptors, possibly of
      the 5-HT1B subtype.

PMID- 7631901
TI  - Characterization and regulation of cold-induced heat shock protein expression in
      mouse brown adipose tissue.
AB  - The accumulation of heat shock proteins (HSPs) after the exposure of cells or
      organisms to elevated temperatures is well established. It is also known that a
      variety of other environmental and cellular metabolic stressors can induce HSP
      synthesis. However, few studies have investigated the effect of cold temperature
      on HSP expression. Here we report that exposure of Institute of Cancer Research
      (ICR) mice to cold ambient temperatures results in a tissue-selective induction
      of HSPs in brown adipose tissue (BAT) coincident with the induction of
      mitochondrial uncoupling protein synthesis. Cold-induced HSP expression is
      associated with enhanced binding of heat shock transcription factors to DNA,
      similar to that which occurs after exposure of cells or tissues to heat and other
      metabolic stresses. Adrenergic receptor antagonists were found to block cold
      induced HSP70 expression in BAT, whereas adrenergic agonists induced BAT HSP
      expression in the absence of cold exposure. These findings suggest that
      norepinephrine, released in response to cold exposure, induces HSP expression in
      BAT. Norepinephrine appears to initiate transcription of HSP genes after binding
      to BAT adrenergic receptors through, as yet, undetermined signal transduction
      pathways. Thermogenesis results from an increase in activity and synthesis of
      several metabolic enzymes in BAT of animals exposed to cold challenge. The
      concomitant increase in HSPs may function to facilitate the translocation and
      activity of the enzymes involved in this process.

PMID- 7631903
TI  - Renal response of roosters with diabetes insipidus to infusions of arginine
      vasotocin.
AB  - In a strain of white Leghorn chicken with symptoms of hereditary diabetes
      insipidus (DI) and with elevated circulating levels of the antidiuretic hormone
      arginine vasotocin (AVT), we investigated whether the defect is based on
      nonfunctional endogenous AVT or on a diminished renal response to AVT. DI
      chickens responded to hyposmotic infusions with a higher urine flow and lower
      glomerular filtration rate (GFR) than healthy control birds. Urine osmolality,
      fractional excretion, and clearance of sodium were lower in DI birds while
      potassium values were similar in both groups. Hence, the high urine flow rates of
      the DI birds were predominantly based on a water diuresis. When infused with AVT,
      the GFR and the urine flow of the control birds decreased and urine osmolality
      increased, showing both glomerular and tubular effects of AVT. During AVT
      infusion, the GFR of DI birds increased, urine flow decreased only moderately,
      and urine osmolality was half that of the control birds. In control birds, the
      clearance of sodium was unchanged, whereas that of potassium decreased. In DI
      birds, which experienced a strong natriuresis, the clearance of both sodium and
      potassium increased. These data suggest that the sensitivity of the DI birds to
      AVT is reduced at the tubular level. The AVT-induced increase in GFR may be
      related to vascular effects of high AVT doses, added to the already high basal
      AVT level of the DI birds, in combination with an imbalance in the function of V1
      and V2 receptor subtypes in these chickens.

PMID- 7631904
TI  - Development of metabolic enzyme activity in locomotor and cardiac muscles of the
      migratory barnacle goose.
AB  - Preflight development of the goslings was typified by rapid increases in the
      mitochondrial enzymes of the semimembranosus and heart ventricular muscles
      resulting in near-adult values by 3 wk of age. In contrast, aerobic capacity of
      the pectoralis muscle initially developed slowly but showed a rapid increase
      between 5 and 7 wk of age, in preparation for becoming airborne. Activities of
      glycolytic enzymes in the pectoralis muscle showed similar patterns of
      development as those found for the aerobic enzymes, except for hexokinase, which
      was low at all ages, indicating an adaptation for catabolism of both
      intracellular glycogen and plasma fatty acids in preference to plasma glucose.
      Muscle mass specific activity of citrate synthase in the pectoralis increased by
      only 33% from goslings during the first few days of flight, compared with
      premigratory geese. Activities of anaerobic glycolytic enzymes in the ventricles
      were low, but values for hexokinase, which is involved in the phosphorylation of
      plasma glucose, developed rapidly. Values for lactate dehydrogenase were also
      high, reflecting the capacity of the heart to catabolize plasma lactate.
      Substrate flux supplied by carnitine palmitoyltransferase and oxoglutarate
      dehydrogenase (OGD), in the pectoralis muscles of the premigratory geese, appears
      to have the smallest excess capacities to meet the requirements of sustained
      aerobic flight. The average maximum oxygen uptake for premigratory geese during
      flight, as indicated by values for OGD, is calculated to be 484 ml O2/min (or 208
      ml O2.min-1.kg-1).

PMID- 7631905
TI  - Effects of duodenal and distal ileal infusions of glucose and oleic acid on meal
      patterns in rats.
AB  - The mechanisms mediating the anorexic effects of nutrients in the proximal and
      distal small intestine are not clearly understood. We determined the dose
      dependent effects of duodenal and distal ileal infusions of glucose and oleic
      acid on meal patterns in ad libitum feeding rats. Rats with cannulas in both the
      duodenum and ileum received a 2-h infusion of glucose (0, 800, 1,600, 3,200,
      6,400, or 12,800 mumol/h) or oleic acid (0, 48, 240, 640, or 1,280 mumol/h) into
      the duodenum or ileum at the start of the dark period, and meal patterns were
      monitored for 4 h. Cumulative food intake was inhibited dose dependently by ileal
      as well as duodenal infusion of both glucose and oleic acid. Ileal glucose was
      more inhibitory than duodenal glucose, whereas duodenal oleic acid was more
      inhibitory than ileal oleic acid. Duodenal glucose and oleic acid inhibited
      feeding by decreasing meal frequency; ileal oleic acid decreased only meal size,
      whereas ileal glucose reduced both meal size and frequency. We interpret these
      results to suggest that ileal oleic acid and glucose suppress feeding by
      different mechanisms and that these mechanisms differ from those mediating the
      anorexic responses to oleic acid and glucose in the duodenum.

PMID- 7631906
TI  - Choroid plexus electrolytes and ultrastructure following transient forebrain
      ischemia.
AB  - A temporal profile of lateral and fourth ventricle rat choroid plexus (LVCP and
      4VCP, respectively) tissue injury and recovery was determined using alterations
      in K, Na, and H2O content and ultrastructure after 10 min of transient forebrain
      ischemia (TFI). At 0.5 h postischemia the LVCP displayed a maximum reduction in K
      content by 32% and a significant increase in Na content by 85% and H2O content by
      22%. LVCP tissue K, Na, and H2O content returned to sham values by 24 h
      postischemia. Ultrastructural changes appeared more severe between 0.5 and 12 h
      postischemia, whereas by 24 h, normal ultrastructure was restored. Elevations in
      4VCP tissue Na (P < 0.05) and H2O content, which were less than those in LVCP,
      gradually reached a maximum by 24 h compared with sham. No change in 4VCP tissue
      ultrastructure was observed. These results indicate that the LVCP tissue is more
      vulnerable than 4VCP in the bilateral carotid artery occlusion model but that it
      recovers in a timely manner after TFI. Furthermore, the ability of the LVCP
      tissue to rapidly recover suggests its functional importance in helping to
      restore brain homeostasis.

PMID- 7631907
TI  - Linoleic and linolenic acids are selectively secreted in triacylglycerol by
      hepatocytes from neonatal rats.
AB  - To determine whether specific fatty acids are metabolized differently by neonatal
      liver, hepatocyte cultures from neonatal (age: 5, 11, and 21 days) and adult rats
      were incubated with radiolabeled 18:1, 18:2, or 18:3. At each age, the rate of
      oxidation was highest for 18:3 and lowest for 18:1. Conversely, esterification
      was highest for 18:1 and lowest for 18:3. Fatty acid esterification was of the
      order: day 5 > day 11 > adult > day 21. When incubations contained each of two of
      the above fatty acids, one radiolabeled and the other not, 18:1 inhibited
      oxidation of radiolabeled 18:2 by up to 45% in neonatal hepatocytes. In addition,
      added 18:1 increased glycerolipid accumulation from 18:2 and 18:3. Under these
      conditions, the relative proportion of triacylglycerol secreted in the medium,
      compared with that accumulated in the cells, was two- to fourfold higher for day
      11 and 21 rat hepatocytes. The results suggest that a specific mechanism exists
      in the livers of neonatal rats to spare n-3 and n-6 fatty acids from oxidation
      and instead secrete them in triacylglycerol.

PMID- 7631908
TI  - Central administration of prostaglandin E2 suppresses in vitro cellular immune
      responses.
AB  - Research suggests that the regulation of the function of the immune system by the
      central nervous system (CNS) involves the integrative responses of multiple
      neural systems that affect neuroendocrine and sympathetic nervous systems. To
      determine whether prostaglandin E2 (PGE2) is involved in the modulatory
      mechanisms of immune system function, it was administered
      intracerebroventricularly (ICV) to conscious male rats. One hour later, spleen
      and peripheral blood lymphocytes were collected for culture with nonspecific
      mitogens. ICV administration of PGE2 decreased blood lymphocyte proliferative
      responses to the T-cell mitogens phytohemagglutinin and concanavalin A and
      decreased spleen lymphocyte proliferative responses to phytohemagglutinin and
      lipopolysaccharide (a B-lymphocyte mitogen). ICV administered PGE2 also
      stimulated the activity of the hypothalamic-pituitary-adrenal axis, as reflected
      by increased plasma concentrations of adrenocorticotropic hormone and
      corticosterone. Thus PGE2 may act in the CNS as a hormonal modulator of immune
      system function.

PMID- 7631909
TI  - A comparative study of voiding in rat and guinea pig: simultaneous measurement of
      flow rate and pressure.
AB  - In this study, the voiding phase of the micturition cycle in the anesthetized rat
      and guinea pig is analyzed. In both animals, voiding is characterized by an
      increase in intravesical pressure and then a decrease, which is accompanied by
      flow through the urethra and emission of urine. An ultrasonic flow probe was used
      in both species to measure the flow rate in relation to the intravesical
      pressure. In the (male) rat, so-called high-frequency oscillations are
      superimposed on the decreasing bladder pressure. These oscillations do not occur
      in the guinea pig. It is concluded that the high-frequency oscillations are
      caused by intermittent flow and not by variations in the bladder contraction. The
      intermittent flow most likely is caused by the relaxation and contraction of the
      external urethral sphincter and may have a function in territory marking. In our
      view, it is not likely that the oscillations enhance bladder emptying, as has
      been suggested in the literature.

PMID- 7631910
TI  - Noninvasive predictors of patency for infrapopliteal PTFE bypasses with combined
      arteriovenous fistula and vein interposition technique.
AB  - BACKGROUND: Despite recent increased indications for infrapopliteal prosthetic
      bypass grafts with complementary arteriovenous fistulas, objective documentation
      of improved perfusion to the foot is lacking. In addition, the value of post
      operative noninvasive testing in the prediction of bypass success remains
      unclear. PATIENTS AND METHODS: Over a 3-year period, 41 patients with limb
      threatening ischemia were treated with 41 infrapopliteal 6-mm
      polytetrafluoroethylene (PTFE) bypasses with a complementary arteriovenous
      fistula at our institution. Twenty-four patients were men and 17 were women, with
      an average age 71.3 +/- 8.6 years. Thirty-one patients (76%) had undergone at
      least 1 previous failed ipsilateral arterial bypass. Preoperative and early
      postoperative (less than 1 month) pulse-volume recordings of transmetatarsal
      amplitude (TMA) were available for analysis in 28 patients. Postoperative duplex
      evaluations of graft velocity, fistula patency, and prograde distal arterial flow
      were performed in 26 of the original 41 patients. These data were correlated to
      early graft failure in an attempt to identify specific noninvasive predictors.
      RESULTS: Cumulative primary patency rates of the original 41 patients were 79.0%,
      69.2%, and 63.8% at 1, 2, and 3 years, respectively. The early postoperative TMA
      values ranged from 3 to 50 mm with a mean of 21.6 +/- 14.8 mm (P < 0.001). Twenty
      one patients (75%) had patent grafts on follow-up of 2 to 37 months (mean 18.6).
      The early postoperative TMA in this group of patients was 26.5 +/- 12.4 mm
      compared with 3.3 +/- 2.8 mm in the 6 patients whose grafts failed within 6
      months (P < 0.001). A TMA of < 5 mm was 83% sensitive and 95% specific for the
      prediction of early graft failure. Of the graft examined by duplex
      ultrasonography, 21 (81%) remained patent during the follow-up period. The
      midgraft peak systolic velocity (PSV) of these grafts was 109 +/- 8.0 cm/s
      compared with 74.2 +/- 15.3 cm/s for the 5 initially patent bypasses that
      subsequently failed at any time during the follow-up period (P < 0.05). PSV of <
      70 cm/s was 60% sensitive and 86% specific in predicting early graft failure. The
      combination of early postoperative TMA < 5 mm and early midgraft PSV < 70 cm/s
      was 100% sensitive and 100% specific for the prediction of early graft failure.
      CONCLUSIONS: These data show that infrapopliteal PTFE arterial bypasses with
      complementary arteriovenous fistulas significantly improve arterial perfusion at
      the level of the foot in the majority of patients. Also, both the postoperative
      TMA and midgraft PSV appear to be reliable predictors of graft outcome. Further
      experience with the noninvasive surveillance of these bypasses may become as
      rewarding as it is in standard vein bypasses.

PMID- 7631911
TI  - Prospective study of the value of prebypass saphenous vein angioscopy.
AB  - BACKGROUND: The patency of a saphenous vein graft is directly related to the
      quality of the vein harvested. Thus, appropriate evaluation of the vein before
      implanting it as a bypass graft may help identify those veins at high risk for
      early failure. Accordingly, we prospectively investigated whether prebypass
      angioscopic assessment of the saphenous vein could identify those vein grafts at
      particularly high risk of early failure. PATIENTS AND METHODS: Thirty-two greater
      saphenous veins with a grossly normal appearance were evaluated angioscopically
      before their use as a bypass conduit. After modification of abnormal segments,
      all of the veins irrigated well and were used as bypass grafts. RESULTS: Twenty
      four patients were available for follow-up at 12 months. Seventeen (71%) had been
      prospectively classified as having angioscopically normal saphenous veins, while
      7 were identified as having abnormal veins. The two groups did not differ
      significantly in demographics, cardiovascular risk factors, or indications for
      operative intervention. Twelve of the 17 (70%) normal veins were patent at 1
      year; however, only 1 (14%) of the angioscopically abnormal vein grafts remained
      patent for 12 months (chi-square = 4.27; P = 0.039). CONCLUSION: Angioscopic
      inspection of the saphenous vein, before insertion as a graft, allows for
      identification of unrecognized venous disease that portends early graft
      thrombosis. Exclusion of abnormal veins, based on an abnormal angioscopic
      appearance, may lead to improved results for lower-extremity revascularization
      procedures; this supports the value of vein-graft angioscopy.

PMID- 7631912
TI  - Choice of peroneal or dorsalis pedis artery bypass for limb salvage.
AB  - BACKGROUND: Arterial bypasses performed for limb salvage have increasingly used
      peroneal and pedal arteries as outflow. However, few reports have been published
      that compare the patency of limb salvage of these alternative outflow tracts. In
      this report, we have examined our experience with peroneal and dorsalis pedis
      (DP) artery bypasses for limb salvage. METHODS AND MATERIALS: Of more than 3,000
      infrainguinal reconstructions performed for limb salvage, 732 were completed to
      the peroneal artery. During the same period, 238 bypasses were performed to the
      DP artery. Patient demographics were similar in both groups. The in situ
      technique was used in 68% of the peroneal bypasses and in 66% of the DP bypasses,
      respectively. Translocated veins were used in 28% of bypasses, and spliced veins
      were used in 32%. RESULTS: Secondary patency rates for the DP bypass at 1 and 5
      years were 89% and 67%, respectively, as compared with 89% and 78% for the
      peroneal artery bypass. Limb salvage rates for the DP bypass were 94% at 1 year
      and 86% at 5 years, as compared with 96% and 93% at 1 and 5 years, respectively,
      for the peroneal artery bypass. No statistical difference was found. Four (1.7%)
      hemodynamic failures occurred in the DP group and 10 (1.4%) in the peroneal
      group. Wound complications were seen in 9 (3%) patients in the DP group and in 11
      (1.5%) in the peroneal group. CONCLUSION: This experience indicates that both
      peroneal and DP bypasses have acceptable patency and limb salvage rates.
      Selection of one of these two outflow tracts, where a choice exists, may depend
      on the conduit limitation and adjacent tissue infection; however, both outflow
      tracts are durable and hemodynamically effective for limb salvage.

PMID- 7631913
TI  - Factors influencing limb salvage and survival after amputation and
      revascularization in patients with end-stage renal disease.
AB  - BACKGROUND: Critical lower-extremity ischemia in patients with end-stage renal
      disease is associated with high operative mortality and low rates of limb
      salvage. PATIENTS AND METHODS: The outcomes of 102 operations for lower-extremity
      ischemia in 77 patients with end-stage renal disease were analyzed to determine
      predictors of limb salvage and operative survival. RESULTS: Patients undergoing
      amputation (n = 50) and revascularization (n = 52) were similar in age, cause,
      and duration of renal failure, and prevalence of coronary artery disease.
      Operative mortality was 13% in revascularized patients and 20% in amputated
      patients, and was caused by sepsis in 12 of the 17 deaths (71%). Limb salvage in
      surviving patients was 91% at 30 days and 67% at 1 year. One-year survival was
      72% in both groups. Factors associated with limb loss included advanced
      generalized atherosclerosis, extensive tissue necrosis, failed ipsilateral
      bypass, and poor cardiac functional status. Overall, factors associated with
      mortality included failure of limb salvage procedures, hemodynamic instability,
      and poor cardiac functional status. CONCLUSIONS: More liberal use of primary
      amputation for end-stage renal disease patients with critical leg ischemia
      appears to be an important factor in improving both limb salvage rates and
      overall operative mortality.

PMID- 7631914
TI  - Early experience with a new ePTFE vascular prosthesis for hemodialysis.
AB  - BACKGROUND: An expanded polytetrafluoroethylene (ePTFE) graft for hemodialysis
      designed for immediate cannulation was tested. The graft contains a cannulation
      segment consisting of a stretch ePTFE base tube surrounded by flat and round
      ePTFE fibers that are secured by a thin, perforated ePTFE cover. This study
      reports our early experience with this new vascular prosthesis. PATIENTS AND
      METHODS: Between June 1994 and March 1995, 48 arteriovenous grafts were implanted
      in 47 patients for whom autogenous fistula construction was impossible. Mean
      patient age was 57 years (range 37 to 85), 86% of the patients were black, and
      60% were men. Twenty-two (46%) grafts were in the forearm, 19 (39%) in the upper
      arm, and 7 (15%) in the groin. Unassisted and assisted patency rates were
      calculated by the Kaplan-Meier method. The times of first hemodialysis relative
      to implantation and the times to hemostasis after first decannulation were
      recorded. Explanted grafts were histologically evaluated with hematoxylin and
      eosin and Gram's stains. RESULTS: The unassisted and assisted 6-month patency
      rate were 42% and 73%, respectively. Five of the first 10 graft were lost to
      management and technical errors, after which the respective patency rates were
      56% and 82%. Eleven of 22 thrombosed grafts were salvaged, 9 with urokinase
      thrombolysis and 2 with surgical thrombectomy. Twenty-eight grafts were
      cannulated within 7 days. The time to hemostasis was usually 2 to 4 minutes and
      always less than 15 minutes. Histologic analysis of a graft explanted at 40 days
      showed good fibrous incorporation and capillary ingrowth between the cover and
      round fibers. CONCLUSIONS: This new ePTFE vascular prosthesis can be safely
      cannulated immediately after implantation, avoiding the morbidity of temporary
      central venous catheter hemodialysis. After an initial period of familiarization,
      patency similar to that of other ePTFE arteriovenous grafts was achieved. For
      patients requiring urgent hemodialysis, this graft is an ideal alternative that
      allows immediate, safe cannulation.

PMID- 7631915
TI  - Recommendations for initial antibiotic treatment of extracavitary arterial graft
      infections.
AB  - BACKGROUND: Initial antibiotic treatment of extracavitary arterial graft
      infections is usually empiric or based on Gram's stain findings. Increasing
      virulence of bacteria causing extracavitary arterial graft infections may render
      previous choices of antibiotics obsolete. The purposes of this study were to
      correlate Gram's stain findings of gram-positive bacteria and gram-negative
      bacteria with wound cultures and provide a microbiologic basis for appropriate
      initial antibiotic therapy. METHODS: Between July 1, 1979 and June 30, 1994,
      specimens obtained on the day of admission from purulent wounds involving 113
      extracavitary arterial graft infections were retrospectively reviewed for Gram's
      stain and culture and sensitivity results. RESULTS: Gram's stain findings
      correlated with final cultures on only 28 of 113 cases (25%), including 20 of 48
      pure gram-positive, 2 of 24 pure gram-negative, and 6 of 41 mixed bacterial
      cultures. Staphylococcus aureus was the most common gram-positive bacteria
      cultured (43 isolates) and Pseudomonas species was the most common gram-negative
      bacteria (25 isolates). Bacteria were sensitive to a first-generation
      cephalosporin in only 32% (36 of 113) of infections. A combination of vancomycin
      and either ticarcillin-clavulanic acid or ceftazidime, which have minimal
      toxicity and provide excellent coverage against staphylococci, Pseudomonas, and
      other gram-negative bacteria, would have covered 96% (109) and 95% (107) of
      cultured organisms, respectively. CONCLUSIONS: Regardless of Gram's stain
      findings, current recommendations for initial treatment of extracavitary arterial
      graft infections should include vancomycin and ceftazidime or ticarcillin
      clavulanic acid until final culture and sensitivity results dictate the use of
      more selective antibiotics.

PMID- 7631916
TI  - Computerized angiographic analysis of the outcome of peripheral thrombolysis.
AB  - BACKGROUND: Catheter-directed peripheral thrombolysis is used increasingly for
      the management of acute limb ischemia. The comparison of different agents and
      techniques has proven difficult because of the variations in patient
      presentation, vessel involvement, and treatment methods. METHODS: A computerized
      database in which angiographic information is stored on computerized arterial
      maps has been designed to record details of thrombolysis. RESULTS: A total of 201
      patients who presented with rest pain were recorded on the database, and their
      angiograms were analyzed. There were 123 native-vessel and 78 graft occlusions.
      Immediate success of lysis and 30-day outcome were not dependent on the site of
      the occlusion. If an underlying stenosis was revealed, limb salvage rates were
      significantly greater than when none was found (82% versus 58%, P < 0.01). The
      presence of at least 1 run-off vessel increased limb salvage rates by 30% (P <
      0.001). If more than 5 arterial segments were occluded on the prelysis angiogram,
      limb salvage was worse than if there were fewer than 5 (57% versus 85%, P <
      0.0001). For grafts, less than 5 segments of occlusion led to limb salvage rates
      of 90%, and more than 5 segments of occlusion led to rates of 72% (P = 0.07).
      CONCLUSIONS: This simple and user-friendly system of computerized angiographic
      analysis will enable detailed examination of thrombolytic practice and assist in
      the prediction of success.

PMID- 7631917
TI  - Occluded infrainguinal grafts: when to choose lytic therapy versus a new bypass
      graft.
AB  - BACKGROUND: The published results of thrombolysis for occluded bypass grafts,
      including a prospective multicenter trial, have been disappointing, prompting
      many investigators to proceed directly to a new bypass rather than attempt graft
      salvage. Our series of 61 occluded grafts treated with lytic therapy, however,
      identified a subgroup that justified attempted graft salvage. METHOD: The grafts
      consisted of saphenous vein 59% (36/61), other vein (arm or composite vein) 21%
      (13/61), and polytetrafluoroethylene (PTFE) 29% (13/61). The data analysis was
      designed to identify the graft subgroup that would benefit from lytic therapy by
      using cumulative survival analysis techniques with the Wilcoxon (Gehan) test for
      univariate analysis and Cox proportional hazards model for multivariate analysis.
      Specific variables examined by univariate analysis were graft age (defined as the
      interval from initial bypass to graft lysis), graft material, graft type
      (femoropopliteal versus femorotibial), diabetes, symptoms (claudication versus
      salvage) and duration of occlusion prior to lysis. RESULTS: Complete lysis was
      achieved in 72% (44/61) of the grafts, and 86% (38/44) had an underlying stenosis
      that was treated by percutaneous balloon angioplasty (28/38) or surgery (7/38).
      Three stenotic outflow lesions were not treated. Cumulative 5-year patency for
      all 61 grafts was 23% +/- 0.075 (SE). Only graft age < 10 versus > 10 months was
      significant (P < 0.004) by univariate analysis, and it was also the only
      significant variable found by multivariate analysis; it indicated a 1.58 increase
      in relative risk of occlusion for the younger grafts. The combination of a
      saphenous vein graft that was also > 10 months old resulted in a 45% 5-year
      patency, compared to 21% for < 10-month-old saphenous vein grafts (P < 0.008). A
      review of 161 bypass grafts performed at our institution over the past 10 years
      revealed a 52% 5-year secondary patency in previously bypassed limbs, which
      varied with graft material (67% saphenous, 50% alternative vein, 31% prosthetic).
      Lysed graft patency was comparable to that of a second bypass using other veins
      or PTFE conduit. CONCLUSIONS: In the absence of an intact saphenous vein for a
      second bypass, thrombolytic therapy is an alternative to surgery.

PMID- 7631919
TI  - Appropriate frequency of carotid duplex testing following carotid endarterectomy.
AB  - BACKGROUND: The value of carotid duplex analysis is well proven for the diagnosis
      of carotid bifurcation occlusive disease, but its use in the postoperative
      setting is less well defined. PATIENTS AND METHODS: A series of 281 carotid
      endarterectomies were performed in 222 patients. A protocol of serial duplex
      examinations was established, with tests performed at the time of the first
      postoperative clinic visit and every 6 months thereafter. The goal of
      postoperative surveillance was to identify critical restenotic carotid lesions of
      greater than 80% diameter reduction and determine the incidence of subsequent
      carotid occlusion and neurologic events. RESULTS: Critical restenoses developed
      in 25 (8.9%) of the arteries and occlusions occurred in 12 (4%). Restenosis
      occurred with greatest frequency during the first year after operation (5%), but
      continued to develop with a frequency of approximately 2% per year thereafter.
      Postoperative carotid occlusions occurred at a rate of approximately 1% per year.
      Known restenotic lesions progressed to occlusion over a mean duration of 11
      months. Stroke was infrequent in patients with critical restenoses (4%) until the
      lesions progressed to occlusion (33%). CONCLUSIONS: These observations suggest
      that a protocol of semiannual duplex testing into the late postoperative period
      may identify critical carotid restenotic lesions prior to the development of
      carotid occlusion and stroke.

PMID- 7631918
TI  - Are one-day admissions for carotid endarterectomy feasible?
AB  - BACKGROUND: In 1990, a clinical pathway for streamlining the care of patients
      undergoing elective carotid endarterectomy was developed and tested at our
      institution. This consisted of extensive preoperative patient education in the
      surgeon's office, outpatient arteriography (now performed only on select
      patients), same-day admission, regional anesthesia when possible, selective use
      of the intensive care unit (ICU), and early discharge in the first postoperative
      day when feasible. PATIENTS AND METHODS: Between January 1, 1991 and June 30,
      1994, 186 patients were entered into the protocol. Twenty-six percent of the
      patients were asymptomatic, while 74% had either transient symptoms or a prior
      stroke; 13% were operated on under general anesthesia. RESULTS: Three (1.6%)
      patients developed neurologic complications: 1 minor stroke, 1 transient ischemic
      attack, and 1 intracerebral hematoma; and 18 (10%) patients required the ICU
      postoperatively. On the first postoperative day, 157 patients were discharged.
      Average operative time was 48 minutes (range 39 to 61). Average length of stay
      (LOS) was 1.27 days. One death occurred on the 28th postoperative day from
      cardiac causes, and there were no hospital readmissions. Cost savings were over
      $3,000/patient when compared to the diagnosis-related group reimbursement.
      Because of the distribution of the data, statistical analysis was not feasible;
      however, several trends were clear. Neurologic complications, admission to the
      ICU, and increasing LOS all diminished the cost efficiency of carotid
      endarterectomy. Type of anesthesia and the use of a shunt or patching did not
      affect cost. Clearly, increasing the length of operation would also decrease cost
      efficiency. CONCLUSIONS: Adoption of the clinical pathway presented here is
      feasible in any institution. One-day admission for patients undergoing carotid
      endarterectomy has been shown to be safe, highly cost-effective, and results in
      more efficient use of scarce resources, such as the ICU.

PMID- 7631920
TI  - Stump pressure, electroencephalographic changes, and the contralateral carotid
      artery: another look at selective shunting.
AB  - BACKGROUND: Selective shunting during carotid endarterectomy is associated with
      the lowest operative stroke rate; therefore, patient selection for carotid
      shunting is critical. Electroencephalography (EEG) can detect ischemic brain cell
      dysfunction before irreversible injury. The carotid stump back pressure (CSP) has
      been inconsistent in determining the need for shunting, and contralateral carotid
      disease has had a variable impact. The purpose of this study was to evaluate CSP
      and operative EEG changes, and to determine the effect of contralateral carotid
      artery disease on determining the need for carotid shunting. METHODS: In 140
      consecutive carotid procedures, operative EEG and CSP were monitored, and
      contralateral carotid disease was documented. The carotid stump pressure/mean
      arterial pressure index (CSP/MAP) was also calculated to determine if this was a
      better indicator of the need for shunting than the CSP alone. RESULTS: There was
      a 58% incidence of EEG changes when the CSP was < or = 25 mm Hg, 32% with a CSP
      of 26 to 50 mm Hg, and 4% with a CSP > 50 mm Hg. There was a 43% incidence of EEG
      changes and lower CSP among patients with a contralateral occlusion, both of
      which were significantly different from patients with a patent contralateral
      carotid artery. Three patients with CSP > 50 mm Hg had EEG changes, but none had
      a contralateral occlusion. Two patients had permanent neurologic deficits, and 2
      had transient deficits. Excluding combined procedures, operative stroke rate was
      0.8%. CONCLUSIONS: A CSP of < 50 mm Hg achieved a sensitivity of 89% in patients
      who developed ischemic EEG changes during carotid clamping, and a pressure > 50
      mm Hg had a negative predictive value of 96%. However, a CSP of < 50 mm Hg had a
      positive predictive value of only 36%. Neither the addition of the status of the
      contralateral carotid artery or the calculation of the CSP/MAP improved the
      sensitivity of the CSP in determining the need for shunting. Operative EEG
      monitoring remains the most sensitive guide to carotid shunting in patients
      undergoing carotid endarterectomy under general anesthesia.

PMID- 7631922
TI  - Cerebral microembolism during carotid endarterectomy.
AB  - BACKGROUND: This study was designed to assess the intraoperative risk of cerebral
      microembolism, as detected by transcranial Doppler ultrasonography, during
      carotid endarterectomy. PATIENTS AND METHODS: Thirty-six patients (37 procedures)
      with symptomatic (n = 35) or asymptomatic (n = 2) internal carotid artery origin
      stenosis(> 50%) were monitored continuously during carotid endarterectomy.
      Special instrumentation was used to detect high-intensity transient signals
      (HITS) in the middle cerebral artery on the carotid endarterectomy side. All HITS
      satisfied a priori established criteria. RESULTS: The incidence of carotid
      endarterectomies with formed-element HITS increased at clamp release (23/37, P <
      0.001) and shunt opening (7/11, P = 0.014), and during wound closure (13/22, P<
      0.005) and shunting (5/11, P = 0.046). HITS with air microbubble characteristics
      were detected at clamp release (22/37, P < 0.001) and shunt opening (5/11, P =
      0.025). CONCLUSIONS: HITS do not occur randomly during carotid endarterectomy.
      Shunting, unclamping, and wound closure are high-risk periods.

PMID- 7631921
TI  - Detection of total occlusion, string sign, and preocclusive stenosis of the
      internal carotid artery by color-flow duplex scanning.
AB  - BACKGROUND: Stroke prevention depends on the accurate differentiation of
      surgically treatable preocclusive lesions from total occlusions of the internal
      carotid artery. This prospective study was undertaken to review the accuracy of
      colorflow duplex scanning for identifying carotid string signs, focal
      preocclusive lesions (95% to 99% stenoses), and total occlusion of the internal
      carotid artery. MATERIALS AND METHODS: Over an 18-month period, 4,362 patients
      underwent color-flow duplex scanning of the carotid arteries. Angiograms of 596
      internal carotid arteries were available for comparison with the duplex scan
      findings. Total occlusion was diagnosed by the absence of flow in internal
      carotid arteries visualized on B-mode scanning. Preocclusive lesions were
      identified by a trickle of flow in the vessel lumen. RESULTS: Of 65 color-flow
      duplex scans that predicted total occlusion, 64 (98%) were confirmed by
      angiography. The negative predictive value for total occlusion was 99%. Twenty
      six (87%) of 30 string signs and focal 95% to 99% stenoses were correctly
      identified. Color-flow scanning prediction of preocclusive lesions was accurate
      in 84% of 31 cases. Low velocities in the internal carotid artery were usually
      associated with a string sign, and high velocities with a focal preocclusive
      lesion. CONCLUSIONS: Color-flow duplex scanning accurately differentiates between
      stenotic and totally occluded internal carotid arteries. Identification of
      preocclusive lesions is not as accurate but the results are promising.
      Arteriographic confirmation of duplex scan findings is necessary only when scans
      are equivocal.

PMID- 7631924
TI  - Incorporation of endovascular training into a vascular fellowship program.
AB  - BACKGROUND: Despite expanding indications for endovascular therapy of peripheral
      vascular disease, vascular surgeons have largely remained bystanders in the use
      of this form of treatment for the disease, which is the focus of their
      profession. Lack of access to training in endovascular techniques is a major
      obstacle to increasing involvement by vascular surgeons. This paper reports our
      experience in the endovascular training of vascular surgical fellows without the
      involvement of radiologists. METHODS: The results of vascular surgery fellows
      receiving instruction in endovascular diagnostic and therapeutic procedures from
      vascular surgery faculty were reviewed. RESULTS: Endovascular training of
      vascular surgery fellows exceeded the case levels recommended by all involved
      societies. A diverse case mix of 355 endovascular diagnostic procedures were
      performed with a major complication rate of 0.3% and no procedure-related deaths.
      Two hundred six endovascular interventions were performed, with an initial
      technical success rate of 96.6%, a 30-day success rate of 93%, no major
      complications, and an overall intervention-related mortality rate of less than
      1%. CONCLUSIONS: Vascular surgery fellows can receive endovascular training by
      vascular surgery faculty without the involvement of radiologists and can do so
      with acceptable success and complication rates. This experience is sufficient to
      qualify them to perform and teach endovascular therapy in their future practices.

PMID- 7631926
TI  - Transfemoral endovascular repair of iliac artery aneurysms.
AB  - PURPOSE: This report evaluates the application of transfemoral endovascular
      repair of iliac artery aneurysms. PATIENTS AND METHODS: Over a 20-month period,
      11 patients with serious comorbid illnesses and a total of 14 iliac artery
      aneurysms were treated with endovascular grafts composed of
      polytetrafluoroethylene conduits combined with balloon expandable iliac artery
      stents (Palmaz). Nine right common, 3 left common, and 2 right internal iliac
      artery aneurysms were treated. The patients were men between 58 and 89 years of
      age (mean 72). Eight patients had isolated aneurysms and 3 had multiple iliac
      artery aneurysms. RESULTS: Endovascular iliac grafts were successfully placed in
      all 11 patients. No procedural deaths occurred. Follow-up ranged from 3 to 21
      months (mean 11). No acute or late graft thromboses occurred. CONCLUSIONS:
      Transluminally placed endovascular stented grafts can be used to successfully
      exclude iliac artery aneurysms from the circulation while maintaining lower
      extremity arterial perfusion. However, longer follow-up in more patients is
      necessary to confirm the durability of this technique.

PMID- 7631923
TI  - Long-term follow-up of patients undergoing carotid endarterectomy in the presence
      of a contralateral occlusion.
AB  - BACKGROUND: Patients with stenosis of one carotid artery and occlusion of the
      contralateral carotid artery (stenosis-occlusion) who are treated medically are
      at high risk for stroke. We have recently reported that carotid endarterectomy on
      the stenotic artery has a low perioperative risk in these patients. We now
      present follow-up data to define the long-term effectiveness of this operation.
      PATIENTS AND METHODS: From 1985 to 1991, 135 patients with stenosis-occlusion
      underwent endarterectomy of the stenotic carotid artery. Selective intra-arterial
      shunting was performed based on mental status changes under regional anesthesia,
      preoperative neurologic deficit, or evidence of preoperative cerebral infarction
      on computed tomography scan. Shunting was used in 70 patients (52%). Saphenous
      vein was used for patch closure in 132 patients (98%), and
      polytetrafluoroethylene in 3 (2%). RESULTS: By life-table analysis, 92% of
      patients have remained stroke-free at 5 years. Fourteen deaths, none related to
      cerebrovascular disease, have occurred during follow-up. The life-table
      cumulative stroke-free survival rate at 5 years is 74%, and the overall survival
      rate is 82%. CONCLUSION: Carotid endarterectomy in the presence of a
      contralateral occlusion provides long-term benefit to the patient with respect to
      prevention of stroke. With lower perioperative stroke rates and proven long-term
      benefit, carotid endarterectomy of the stenotic artery should be the treatment of
      choice in the patient with stenosis-occlusion.

PMID- 7631925
TI  - Delayed rupture of aortic aneurysms following endovascular stent grafting.
AB  - BACKGROUND: Deployment of transfemoral, endovascular stent grafts for treatment
      of abdominal aortic aneurysms is appealing for several reasons: avoidance of
      abdominal incision, lack of aortic cross-clamping, potential for regional
      anesthesia, and shortened hospital stay. Concerns remain, however, regarding the
      ability of these devices to completely exclude the aneurysm and prevent aneurysm
      rupture and the long-term integrity of the device. The availability of endografts
      and the likely development of percutaneous devices have also raised the delicate
      issue of personnel training for patient selection, endograft implantation, and
      postoperative follow-up. PATIENTS AND METHODS: The cases of 2 patients are
      reported in which Dacron endovascular grafts, anchored proximally and distally by
      Palmaz stents, were deployed for treatment of infrarenal abdominal aortic
      aneurysms. RESULTS: In a patient with and absent distal cuff, choosing this
      procedure represented a clear error in patient selection. The endograft failed to
      reach the aortic bifurcation and the aneurysm ruptured, with the death of the
      patient 4 months postimplantation. In a patient with anatomy suitable for
      endograft placement, a perigraft leak persisted at the distal anastomosis
      following device placement. The aneurysm ruptured 14 days postprocedure. Although
      the patient survived emergent aneurysm repair, he developed acute renal failure.
      CONCLUSION: Careful preoperative assessment of aortic anatomy is crucial in
      selection of patients for transfemoral endovascular graft placement. Lack of a
      distal cuff of at least 1 cm precludes tube graft implantation. Patients with a
      perigraft leak are not protected by the endograft from aneurysm rupture. Vascular
      surgeons must be involved in the preoperative evaluation of these patients and
      are the only specialty group who can provide the prerequisite care in evaluation
      and management of postoperative complications.

PMID- 7631927
TI  - Selection of patients for renal artery repair using captopril testing.
AB  - BACKGROUND: Prediction of improvement following surgical or radiologic
      intervention in patients thought to have renovascular hypertension (RVH) is often
      unreliable. Use of the angiotensin-converting enzyme inhibitor captopril in
      conjunction with measurement of peripheral renin levels or radioisotope renograms
      is thought to detect patients with functionally significant renal artery
      stenosis. However, it is unclear whether these tests can identify patients whose
      hypertension will significantly improve after renal artery repair. PATIENTS AND
      METHODS: The records of 52 consecutive hypertensive patients undergoing captopril
      studies followed by renal artery repair were reviewed. All patients had either
      renal artery stenosis > 75% or renal artery occlusion. Preprocedure evaluation
      included a captopril challenge test (measurement of peripheral renin levels after
      captopril ingestion) (n = 12) or a captopril renogram (determination of renal
      blood flow and glomerular filtration rate before and after captopril
      administration) (n = 40). Either renal artery bypass/nephrectomy (n = 41) or
      balloon angioplasty (n = 11) was done in all patients (18 bilateral/34
      unilateral). No periprocedural deaths occurred. All surgically placed bypass
      grafts were shown to be patent by contrast or carbon dioxide arteriography before
      hospital discharge. RESULTS: Preprocedure captopril tests were positive
      (suggestive of RVH) in 39 patients (75%) and negative in 13 (25%). All patients
      with positive captopril tests had improvement in their RVH after intervention (17
      cured, 22 improved) while 8 of 13 patients with negative captopril tests had no
      improvement in blood pressure control. Four of five false-negative tests were
      associated with a unilateral total renal artery occlusion, making detection of a
      postcaptopril effect impossible. If these 4 patients are excluded from analysis,
      preprocedure captopril testing was 98% accurate in predicting postprocedure
      outcome. CONCLUSIONS: Preprocedure captopril testing permits extremely accurate
      selection of patients with renal artery stenosis who will benefit from renal
      artery repair.

PMID- 7631928
TI  - Limb salvage and patency after aortic reconstruction in younger patients.
AB  - PURPOSE: The purpose of this report was to compare patient characteristics,
      treatment, and outcome in younger and older patients with aortoiliac occlusive
      disease. METHODS: The medical records of 56 patients < or = 50 years of age
      (Group < or = 50) were retrospectively reviewed and compared to the records of
      128 patients > or = 60 years of age (Group > or = 60). All patients were examined
      and treated between April 1987 and April 1994. Postoperatively, they were
      enrolled in a vascular laboratory surveillance program to serially monitor the
      status of the vascular reconstruction. Follow-up averaged more than 3 years in
      both groups and was available on greater than 90% of patients. RESULTS: Patients
      in Group < or = 50 had a higher incidence of smoking (68% versus 51%) and a lower
      incidence of hypertension (29% versus 50%) than patients in group > or = 60
      (smoking P = 0.03, hypertension P = 0.007). No other significant differences were
      noted among cardiovascular risk factors. Preoperative indications for surgery
      were similar among patients in both groups. An aortoiliac endarterectomy was more
      commonly used to revascularize the lower extremities in younger patients than in
      their older counterparts (23% versus 7%, P = 0.002). Graft revisions were more
      frequently necessary after aortic reconstruction in Group < or = 50 than in Group
      > or = 60 (29% versus 8%, P = 0.0003); however patency rates computed by life
      table analysis were not significantly different. The primary patencies for Group
      < or = 50 and Group > or = 60 at 5 years were 64% and 67%, respectively; their
      secondary patency rates at 5 years were 84% and 89%, respectively. No significant
      difference was found in major limb amputation (8% in Group < or = 50 versus 5% in
      Group > or = 60, P = 0.46). We conclude that aortoiliac reconstruction for
      occlusive disease can be performed with similar secondary patency and amputation
      rates in young and old patients. However, close postoperative surveillance and
      frequent surgical revision are necessary to maintain patency and minimize
      amputation.

PMID- 7631929
TI  - Transforming growth factor-beta 1 inhibits human arterial smooth-muscle cell
      proliferation in a growth-rate-dependent manner.
AB  - BACKGROUND: Proliferation of arterial smooth-muscle cells is central in the
      development of both atherosclerosis and intimal hyperplasia. The cytokine
      transforming growth factor-beta 1 (TGF-beta 1) is known to have variable effects
      on smooth-muscle cell proliferation. Using human arterial smooth-muscle cells, we
      sought (1) to define the serum concentrations required to maintain cellular
      proliferation; and (2) to define the effects of TGF-beta 1 on smooth-muscle cell
      proliferation. METHODS: Smooth-muscle cell cultures were established from the
      normal aorta of transplant donors. Cells were grown to subconfluent and confluent
      densities, then incubated in either serum-free media, or 1% or 10% fetal bovine
      serum (FBS) enhanced media. Cellular proliferation was assayed by cell counting
      at 24, 48, and 96 hours to establish growth rate. Identical experiments with the
      addition of recombinant human TGF-beta 1 (5 ng/mliters) were also performed.
      Studies were done in triplicate for each group, and results expressed as the mean
      +/- SE. Groups were compared by analysis of variance. RESULTS: In subconfluent
      cultures, only smooth-muscle cells in 10% FBS proliferated, whereas growth arrest
      occurred in serum-free media and 1% FBS. In confluent cultures, cells in all
      media conditions proliferated. TGF-beta 1 had an inhibitory effect in actively
      proliferating cultures. There was a positive correlation between the inhibitory
      effects of TGF-beta 1 and smooth-muscle cell growth rate (r = .65; P = 0.005).
      CONCLUSIONS: When confluent, human arterial smooth-muscle cells continue to
      proliferate after serum deprivation, suggesting that these cells are capable of
      conditioning their own medium. TGF-beta 1 inhibits smooth-muscle cell
      proliferation in a growth-rate-dependent manner. These data suggest that TGF-beta
      1 may have a growth-regulatory role in vascular disease by counteracting states
      of arterial smooth-muscle cell proliferation.

PMID- 7631930
TI  - Antiphospholipid antibodies lead to increased risk in cardiovascular surgery.
AB  - BACKGROUND: Antiphospholipid (APL) antibodies are a heterogenous group of
      antibodies that have been associated with an increase in bleeding complications
      and a marked increase in thrombotic events, both of which result in significant
      patient morbidity and mortality. PATIENTS AND METHODS: A retrospective analysis
      of patients identified to be positive for APL via a university thrombosis
      registry who had cardiovascular surgery between 1989 and 1994. RESULTS: Seventy
      one patients positive for APL antibodies were identified. Of those patients, 19
      had cardiovascular surgical procedures (11 women and 8 men, mean age 58.4 years,
      range 38 to 78). A total of 48 cardiovascular surgical procedures (mean 2.5
      procedures/patient) were performed in the 19 patients. These procedures included
      13 lower-extremity reconstructions, 11 upper-extremity reconstructions/fistulas,
      8 cardiac valve replacements, 5 coronary artery bypass procedures, 5 major
      amputations, 4 infrarenal aortic reconstructions, and 2 carotid endarterectomies.
      Sixteen of the 19 patients (84.2%) suffered major postoperative complications.
      These included 16 thrombosed grafts, 5 strokes, 5 major bleeding events, 2
      pulmonary emboli, and 2 myocardial infarctions. Ultimately, 12 of the 19 patients
      (63.2%) died of complications related to surgery. CONCLUSIONS: This series of
      patients confirms that patients with circulating APL antibodies are prone to
      excessive postoperative morbidity and mortality after cardiovascular surgical
      procedures. The presence of APL antibodies may be a maker of increased risk of
      complications after cardiovascular surgery.

PMID- 7631932
TI  - A comparison of conservative therapy and early selective ligation in the
      treatment of lymphatic complications following vascular procedures.
AB  - BACKGROUND: Lymphatic leakage is a relatively uncommon but serious complication
      following vascular procedures. A conservative approach consisting of bed rest,
      leg elevation, prophylactic antibiotics, compressive dressings, and intermittent
      aspiration is the most commonly used treatment. Because of the long time it takes
      to cure this condition and the potential for infections, a more aggressive
      approach consisting of wound exploration and ligation of the leaking lymphatic
      has been proposed. We review our experience of the past 3 years treating 17 of
      these complications by using 1 of these 2 approaches. PATIENTS AND METHODS:
      Seventeen groin complications were seen over a period of 3 years. Ten (59%)
      patients were treated by selective ligation assisted with isosulfan blue dye
      injection, and the remaining 7 (41%) were treated conservatively. RESULTS: Mean
      hospital stay was 2.4 days (range 1 to 4) for the operative group versus 19 days
      (range 14 to 42) for the conservative group. One complication was seen in the
      operative group, whereas 4 (57%) patients developed groin infections following
      conservative therapy. One (10%) patient developed a recurrence following ligation
      that was treated successfully by reoperation. CONCLUSION: Our experience with the
      use of surgical ligation of leaking lymphatic assisted by isosulfan blue, when
      compared with conservative treatment, has led to a decrease in hospital stay,
      lower complication rates, and fewer recurrences. In our view, this approach
      represents the best form of treatment for postoperative groin lymphatic
      complications.

PMID- 7631931
TI  - Selective use of the duplex scan in diagnosis of deep venous thrombosis.
AB  - BACKGROUND: The introduction of managed care, with its emphasis on cost
      containment, makes it of paramount importance that all tests ordered be specific,
      selective, and appropriate. METHOD: The data concerning patients who underwent a
      duplex scan to determine the presence of deep venous thrombosis (DVT) over a 68
      month period, were reviewed in order to determine if the test was ordered
      appropriately. The symptoms that prompted the test, type of physician ordering
      the test, and demographic data for both the patients who tested positive and
      negative were tabulated. RESULTS: A total of 2,841 duplex scans were ordered over
      a 68-month period for presumptive diagnosis of DVT of an extremity. A total of
      524 (18%) scans were positive for thrombosis; however, 27% (144) of these were
      superficial or a small isolated thrombus in the calf or forearm. Thus, only 380
      studies, or 13% of the total scans ordered, were positive for a major DVT
      requiring treatment. The only symptoms consistently found in the positive group
      were pain, edema, dyspnea, and a history of DVT. Of the types of physicians
      ordering the test, emergency department physicians were least specific, with only
      12% of the scans ordered being positive for DVT; surgeons were more selective and
      had a 19% positive rate, while internal medicine physicians had a 20% positive
      rate. CONCLUSION: The duplex scan allows the physician the ability to easily
      diagnose venous thrombosis, but its indications need to be more carefully guided
      by history, physical examination, risk factors, and logic to enhance its use and
      effectiveness. This study analyzes the risk factors and symptoms involved in
      order to assist the clinician in determining when the duplex scan is indicated.

PMID- 7631933
TI  - Peripheral vascular complications of aortic dissection.
AB  - BACKGROUND: The incidence and management of peripheral vascular complications of
      aortic dissection is unsettled. PATIENTS AND METHODS: Peripheral vascular
      complications of spontaneous aortic dissection were examined in a 5-year
      retrospective review. Patients who had peripheral vascular complications were
      categorized as group A; those without as group B. RESULTS: Thirty-eight major
      vessels were affected in 18 patients. No patient underwent a peripheral vascular
      procedure for complications of the carotid, subclavian, celiac, mesenteric, or
      renal arteries. Three patients underwent femorofemoral bypass for acute
      iliofemoral occlusion due to dissection. A fourth patient had repair of an iliac
      aneurysm that developed as a complication of chronic dissection. The mortality
      rate was 17% for group A, 9% for group B, and 10% overall. Following repair of
      the aortic dissection, the majority of the peripheral vascular complications
      resolved. CONCLUSIONS: Peripheral revascularization is infrequently required in
      aortic dissection following primary dissection repair.

PMID- 7631934
TI  - Outcome and expansion rate of 57 thoracoabdominal aortic aneurysms managed
      nonoperatively.
AB  - BACKGROUND: The prognosis of thoracoabdominal aortic aneurysms (TAAAs) managed
      nonoperatively is unknown. PATIENTS AND METHODS: To determine the risk of rupture
      and survival, we retrospectively reviewed the clinical course and computed
      tomographic data of 57 patients who were evaluated for degenerative,
      nondissecting TAAAs. Nonoperative management was decided initially for all
      patients. Data of aneurysm expansion rate were available in 29 patients who
      underwent 2 or more scans. Follow-up was complete in 52 (91%) patients and
      averaged 37 months (range 1 to 82). RESULTS: Thirty-four of the 57 (60%) patients
      died during follow-up, including 3 of 15 patients who underwent subsequent repair
      of their aneurysm. Two- and 5-year survival rates for the entire group were 69%
      and 39%, with repair-free survival rates of 52% and 17%, respectively. Eight
      (14%) aneurysms ruptured, accounting for 24% (8/34) of the deaths. Two- and 4
      year risks of rupture were 12% and 32%, respectively. The median expansion rate
      was 0.2 cm/y and was greater in patients with chronic obstructive pulmonary
      disease (P < 0.05). All ruptured aneurysms were > 5 cm in diameter. Aneurysms
      with a diameter > 5 cm at diagnosis had a higher rupture rate than those with a
      diameter < or = 5 cm (P < 0.05). Expansion rate did not predict rupture.
      CONCLUSIONS: Mortality of patients with TAAAs preselected for nonoperative
      management is high, with an overall survival rate of 39% and repair-free survival
      rate of only 17% at 5 years. Expansion rate of TAAAs (0.2 cm/y) is similar to
      that of abdominal aortic aneurysms. Our data that support nonoperative management
      for patients with TAAAs < 5 cm in diameter, but confirm the increase rate of
      rupture for aneurysms > 5 cm.

PMID- 7631936
TI  - Acute peritoneal dialysis following ruptured abdominal aortic aneurysms.
AB  - BACKGROUND: Acute renal failure is common after repair of ruptured abdominal
      aortic aneurysm. Early dialysis has recently been advocated to reduce the
      mortality associated with multiorgan failure, but hemodialysis (HD) is not well
      tolerated in critically ill patients because of hemodynamic instability and risk
      of bleeding from anticoagulation therapy. Peritoneal dialysis (PD) has the
      advantage in that it causes minimal cardiopulmonary instability and does not
      require anticoagulation. The presence of a freshly-closed abdominal wound and an
      aortic graft, however, have previously been considered to be contraindications to
      PD. METHODS: Peritoneal dialysis catheters were placed in 69 of the 105 patients
      who underwent grafting for a ruptured abdominal aortic aneurysm between 1982 and
      1993. Criteria for placement included shock, perioperative oliguria, and
      preoperative renal insufficiency. All charts were reviewed retrospectively to
      evaluate the safety and efficacy of placing PD catheters and initiating early
      dialysis in patients at risk for developing acute renal failure. RESULTS: Acute
      tubular necrosis developed in 31 patients, 19 of whom required dialysis.
      Peritoneal dialysis alone provided effective dialysis in 8 patients, and it was
      combined with hemofiltration and/or HD in 9 additional patients for an overall
      efficacy of 58%. The peritoneal catheter also facilitated the early diagnosis of
      peritonitis due to colon ischemia in 5 patients, and was helpful in diagnosing
      intra-abdominal hemorrhage in 4 others. Bacterial peritonitis occurred in 3 (17%)
      patients undergoing PD with no cause noted for the infection diagnosing other
      than use of the PD catheter. A single aortic graft infection was diagnosed 4.2
      years postoperatively with an enteric organism in a patient with recurrent
      diverticulitis. Two patients with peritoneal catheters developed abdominal wound
      dehiscence, but neither had undergone PD (P > 0.2). In a multivariate analysis,
      placement of a PD catheter did not affect survival. CONCLUSIONS: Placement of a
      PD catheter at the time of resection of a ruptured abdominal aortic aneurysm in
      patients at risk for development of acute renal failure is without significant
      complications and can facilitate early and effective dialysis. The peritoneal
      dialysis catheter may also be useful in making an early diagnosis of
      intraperitoneal bleeding and infection.

PMID- 7631935
TI  - Reducing morbidity of thoracoabdominal aneurysm repair by preliminary
      axillofemoral bypass.
AB  - BACKGROUND: Thoracoabdominal aneurysm (TAA) repair continues to be associated
      with appreciable morbidity and mortality. To reduce the substantial cardiac
      afterload of thoracic aortic clamping, preserve visceral, renal, and lower
      extremity perfusion, and reduce spinal cord ischemia, a right axillofemoral
      bypass was performed before TAA resection. PATIENTS AND METHODS: Fifteen patients
      undergoing repair of their TAA had a preliminary axillofemoral bypass with an 8-
      to 10-mm externally supported polytetrafluoroethylene graft. Nine underwent
      elective repair and 6 were operated on emergently. All but 2 patients (both had
      type IV aneurysms) had spinal fluid drainage and all had moderate hypothermia
      induced (31 degrees C to 32 degrees C). All visible intercostal arteries were
      reimplanted. RESULTS: Requirements for pharmacologic afterload reduction were
      minimal. Urine output was preserved during proximal aortic and intercostal
      anastomoses, and acidosis was minimal. Anticoagulation was not necessary unless
      the aortic bifurcation was replaced, and no patient had thrombotic complications.
      One (7%) patient died after repair of a ruptured aneurysm, and 1 (7%) developed
      paraplegia and required temporary dialysis. CONCLUSION: Preliminary axillofemoral
      bypass avoids the profound hemodynamic and physiologic derangement caused by
      clamping of the thoracic aorta, and effectively reduces the morbidity of TAA
      repair.

PMID- 7631937
TI  - Simultaneous abdominal aortic aneurysm repair and nephrectomy for neoplasm.
AB  - BACKGROUND: Abdominal aortic aneurysm and renal neoplasm are occasionally
      discovered concurrently. Simultaneous operative therapy may be an effective
      alternate management strategy to a staged procedure. PATIENTS AND METHODS: The
      medical records of 10 consecutive patients undergoing abdominal aortic aneurysm
      repair and nephrectomy for renal neoplasm were reviewed. Data collected included
      mode of presentation, preoperative evaluation, renal pathology, and in-hospital
      morbidity and mortality. Long-term follow-up was obtained through office records
      and telephone contact. RESULTS: In 7 patients, the renal mass was identified
      during evaluation of abdominal aortic aneurysm. The aneurysm was identified
      during evaluation of hematuria in 2 patients. One patient was discovered to have
      both conditions simultaneously. All patients underwent successful aneurysm repair
      and nephrectomy. Pathology revealed 6 renal cell carcinomas, 2 complex cysts, 1
      hemangiopericytoma, and 1 oncocytoma. Four patients have died in the follow-up
      period: 1 of metastatic cancer and 3 of unrelated causes. There have been no
      cases of graft infection. CONCLUSION: Simultaneous abdominal aortic aneurysm
      repair and nephrectomy for neoplasm is an appropriate management strategy for
      selected patients.

PMID- 7631938
TI  - Management of synchronous renal cell carcinoma and aortic disease.
AB  - BACKGROUND: We have noted a significant incidence of renal cell carcinoma (RCC)
      detected during evaluation for aneurysmal and aortoiliac occlusive disease. The
      approach to synchronous malignancy and aortic disease (staged versus concurrent
      resection) is controversial, as is the management of incidental RCC (partial
      versus radical nephrectomy). PATIENTS AND METHODS: We reviewed our experience
      with incidental RCC in patients undergoing aortic reconstruction between 1991 and
      1994. Ninety-seven patients underwent aortic reconstruction for aneurysmal (72),
      occlusive (20), or embolic disease (5) during the time frame under review. All
      were men. Of the 80 preoperative computerized tomographic (CT) scans obtained, 7
      (9%) demonstrated renal lesions suspicious for RCC. All lesions were explored and
      excised by partial or radical nephrectomy before heparinization and completion of
      the planned aortic procedure. RESULTS: The overall mortality rate was 3%. None of
      the deaths occurred in patients undergoing combined procedures. Four partial and
      three radical nephrectomies were performed. Of the 7 renal lesions, 2 were
      complex cysts and 5 were RCC. Both patients with complex cysts were treated with
      wedge resection. One patient required surgical drainage of a wound abscess after
      partial nephrectomy. No significant differences were found between preoperative
      (1.4 +/- 0.1 mg/dL) and postoperative (1.8 +/- 0.2 mg/dL) creatinine levels
      following combined procedures. On follow-up CT scans done at 6-month intervals
      (mean follow-up 24 months), no evidence exists of recurrence, metastasis, or
      graft infection. CONCLUSIONS: This patient population demonstrated an
      unexpectedly high prevalence of incidental RCC (5 or 80 CTs, 6%). No increase in
      mortality was found when RCC and aortic disease were treated at the same
      operation. While partial nephrectomy was associated with one wound infection in
      this series, it is an effective treatment for small incidental RCC and may avoid
      unnecessary nephrectomy in patients with benign disease. Base on the high
      incidence of RCC in this population, we recommend exploration of all suspicious
      lesions. Nephrectomy can be performed safely in the same setting as aortic
      reconstruction. Because underlying renal dysfunction is not uncommon in patients
      with aneurysmal and aortoiliac occlusive disease, nephron-sparing surgery should
      be considered.

PMID- 7631939
TI  - Reduced length of stay following carotid endarterectomy under general anesthesia.
AB  - BACKGROUND: The widespread use of diagnosis-related groups has led to a
      significant reduction in the length of hospital stay following many surgical
      procedures. In light of this, an examination of early discharge following carotid
      endarterectomy under general anesthesia was undertaken. PATIENTS AND METHODS: A
      prospective study of 72 patients was conducted, in which the workup was done on
      an outpatient basis, admission took place on the same day as surgery, and
      patients were discharged home on the day after carotid endarterectomy. RESULTS:
      There were no strokes or deaths following carotid endarterectomy, and only two
      transient ischemic attacks occurred. In 88% of the cases, discharge was possible
      on the first postoperative day. CONCLUSIONS: Early discharge following carotid
      endarterectomy under general anesthesia is safe and cost effective.

PMID- 7631940
TI  - Allastair B. Karmody Award. Calf vein thrombi are not a benign finding.
AB  - BACKGROUND: Currently, there is no consensus in the literature regarding which
      patients with calf vein thrombi are at high risk for proximal propagation. This
      study examined patients with isolated calf vein thrombi with serial duplex scans
      in order to identify risk factors that would predict outcome. PATIENTS AND
      METHODS: Between May 1989 and November 1994, 288 patients were identified with
      isolated calf vein thrombi. One hundred ninety-two of them had sequential scans
      performed. RESULTS: Fifty-three (28%) of the 192 patients had propagation of
      their initial thrombi. The most proximal level of propagation was the popliteal
      vein in 11 patients, the superficial femoral vein in 5, the common femoral vein
      in 5, adjacent tibial or soleal veins in 24, adjacent soleal veins alone in 7,
      and the lesser saphenous vein in 1. Three patients whose thrombi propagated had
      free-floating thrombus tips in the large veins of their thighs. Symptoms,
      prophylaxis, and risk factor analysis comparing those patients whose thrombi
      propagated to those whose thrombi did not found no statistically significant
      prognostic value. Single or multiple calf vein thrombi did not predict
      propagation. Of the 23 patients treated with heparin, only 3 had thrombus
      propagation. None of these reached the level of the knee (including popliteal
      vein). CONCLUSIONS: The natural history of distal lower extremity thrombosis does
      not appear to be as benign as previously believed.

PMID- 7631941
TI  - Peter B. Samuels Award. Ruptured abdominal aortic aneurysm repair: the financial
      analysis.
AB  - BACKGROUND: Denial of ruptured abdominal aortic aneurysm (RAAA) repair has been
      advocated based upon historically poor surgical outcome and a perceived lack of
      cost effectiveness. Although the repair intuitively seems expensive, the actual
      cost of care, adequacy of reimbursement, and cost per additional life-year gained
      for RAAA repair are poorly defined. PATIENTS AND METHODS: Retrospective clinical
      and financial chart review of 119 consecutive patients undergoing operation for
      RAAA from 1986 to 1993. RESULTS: Overall in-hospital mortality was 45%. Mean
      institutional charge per patient in 1993 dollars was $40,763 (range $4,473 to
      $284,374), with an actual mean cost for service of $22,420 and an average
      reimbursement of $21,360, resulting in a loss of $1,060 per patient. Losses were
      higher in Medicare patients. Survivors (n = 65) had an average length of stay of
      20 days, cost $41,045 each, and incurred an institutional loss of $298,405. Mean
      cost per additional (adjusted) life-year was $3,953. One-, 3-, and 5-year
      survival rates following hospital discharge were 97%, 85%, and 77%, respectively.
      CONCLUSIONS: Emergency repair of RAAA is relatively inexpensive when compared to
      other commonly used health maintenance protocols and effectively restores
      survivors to their former health. Since no clinical or physiologic parameter can
      predict poor outcome, operative intervention should not be denied.

PMID- 7631942
TI  - The impact of gender on the results of arterial bypass with in situ greater
      saphenous vein.
AB  - BACKGROUND: This 10-year review of in situ saphenous vein bypass surgery was
      undertaken to assess the impact of gender on infrainguinal arterial
      reconstruction. PATIENTS AND METHODS: From March 1983 to March 1993, the results
      of 244 in situ saphenous vein bypasses performed in women were compared with 338
      performed in men. Women were older than men (70.9 versus 66.8 years; P < 0.001)
      and had a higher incidence of hypertension but a lower incidence of coronary
      artery disease, smoking history, and chronic obstructive pulmonary disease. The
      primary indication for surgery was limb salvage for both genders (women 70.1%,
      men 68%; P = not significant [NS]). Men had bypasses to more-distal outflow
      vessels with 52.5% to the tibial level compared with 42.2% of women (P < 0.003).
      RESULTS: Women had lower perioperative mortality rates than men (0.8% versus
      3.3%; P < 0.025) and a similar incidence of major complications (6.6% versus
      7.7%; P = NS), but a higher incidence of significant wound complications (13.5%
      versus 3.3%; P < 0.001). Life-table evaluation at 10 years after surgery showed
      no significant differences between women and men in primary graft patency rate
      (67.8% versus 58.2%; P = NS), secondary patency rate (73.5% versus 77.2%; P = NS
      ), limb salvage rate (87.9% versus 92%; P = NS) or patient survival rate (35.5%
      versus 24.4%; P = NS). For bypasses to the tibial arteries, graft patency rates
      were slightly inferior for women (69.8% versus 81.1%, 5-year secondary patency
      rate; P < 0.008). Similarly, in bypasses performed for limb salvage, women had
      lower 5-year primary patency rates than men (60.3% versus 70.3%; P < 0.002).
      Secondary patency rates in this limb salvage group however, did not differ (75.5%
      versus 82.8%; P = NS). CONCLUSIONS: Despite small gender differences in the
      results of in situ bypass grafts for limb salvage and those carried to the tibial
      level, women had the same overall patency, limb salvage, and survival rates as
      men after infrainguinal bypass surgery. Treatment of infrainguinal occlusive
      disease should not vary based on inaccurate perceptions concerning differences in
      surgical results for men and women.

PMID- 7631943
TI  - Intensive care unit neuromuscular syndrome?

PMID- 7631944
TI  - Multivariate determinants of early postoperative oxygen consumption in elderly
      patients. Effects of shivering, body temperature, and gender.
AB  - BACKGROUND: Previous investigators have proposed that postoperative shivering may
      be poorly tolerated by patients with cardiopulmonary disease because of the
      associated significant increase in total-body oxygen consumption. However, the
      often-quoted 300-400% increase in oxygen consumption with shivering was derived
      from relatively few studies performed in a small number of younger persons
      specifically selected on the basis of clinically recognizable shivering. We
      hypothesized that the average elderly postoperative patient has a shivering
      response that is associated with a relatively small increase in total-body oxygen
      consumption. METHODS: One hundred eleven elderly patients (age > 60 yr)
      undergoing surgery were studied to assess the determinants of shivering and total
      body oxygen consumption in the early postoperative period. Anesthetic technique,
      postoperative analgesia, and thermal management were controlled by protocol. The
      clinical variables associated with shivering and increased total-body oxygen
      consumption were determined by univariate and multivariate analyses. RESULTS:
      Mean total-body oxygen consumption in shivering patients was 38% greater than in
      nonshivering patients. Regardless of whether data from shivering patients were
      included in the analysis, oxygen consumption was directly proportional to mean
      body temperature. Despite similar core temperatures, men had a greater incidence
      of clinically recognizable shivering and greater total-body oxygen consumption
      than did women. CONCLUSIONS: The metabolic demands associated with postoperative
      shivering in elderly patients are less than those reported previously in younger
      persons. These findings suggest that if hypothermia predisposes to cardiovascular
      complications in the postoperative period, these complications are not likely to
      be mediated by shivering and increased metabolism.

PMID- 7631945
TI  - A cost analysis of the laryngeal mask airway for elective surgery in adult
      outpatients.
AB  - BACKGROUND: Since the introduction of the laryngeal mask airway (LMA) into the
      United States in 1991, the device has become widely used in anesthesia practice.
      The purpose of this economic analysis was to use existing data to evaluate the
      costs of the LMA relative to three other common airway management techniques and
      to identify the variables that had the greatest effect on cost efficiency.
      METHODS: We evaluated four airway management techniques for healthy adults
      receiving an isoflurane-nitrous oxide-oxygen anesthetic for elective outpatient
      surgery: (1) LMA with spontaneous ventilation; (2) face mask with spontaneous
      ventilation; (3) tracheal intubation after succinylcholine with subsequent
      spontaneous ventilation; and (4) tracheal intubation after nondepolarizing
      neuromuscular blockade and controlled ventilation. We analyzed published clinical
      studies of the LMA and obtained cost data from Stanford University Medical
      Center. The best available estimates of the independent variables were
      incorporated into a baseline case. For each airway technique we derived cost
      equations that excluded costs common to all four techniques. RESULTS: Relative to
      airway management with an LMA, calculated values for the baseline analysis
      included additional isoflurane costs for use of a face mask ($ 0.12/min) and for
      tracheal intubation with ($ 0.043/min) and without neuromuscular blockade ($
      0.06/min). With a neuromuscular blocking drug cost of $ 0.21/min and an LMA cost
      per use of $ 20, the face mask with spontaneous ventilation was the cost
      efficient airway choice for anesthetics lasting as long as 100 min. Increasing
      the LMA reuse rate from 10 to 25 made the LMA the least costly airway technique
      for cases lasting more than 70 min. CONCLUSIONS: If the LMA is reused 40 times,
      the LMA is the cost-efficient airway choice for outpatients receiving an
      isoflurane-nitrous oxide-oxygen anesthetic lasting longer than 40 min. This
      finding does not change if the cost of neuromuscular blockade or the incidence of
      airway-related complications is varied over a clinically relevant range.

PMID- 7631946
TI  - Effects of exogenous intravenous glucose on plasma glucose and lipid homeostasis
      in anesthetized infants.
AB  - BACKGROUND: Whether intravenous glucose administration to infants during
      anesthesia is necessary remains to be resolved. The current study was designed to
      investigate the effect of exogenous glucose infusion on plasma glucose and lipid
      homeostasis in infants undergoing minor surgery. METHODS: Sixty infants
      (inpatients, ASA physical status 1) between 1 and 11 months of age were divided
      randomly into three groups as follows: LR group, lactated Ringer's solution (LR)
      alone; D2LR group, 2% glucose in LR; and D5LR group, 5% glucose in LR. Anesthesia
      was induced and maintained with halothane and nitrous oxide in oxygen. All fluids
      were infused at a rate of 6 ml.kg-1.h-1 until 1 h after surgery. Plasma
      concentrations of glucose, nonesterified fatty acids, ketone bodies, insulin, and
      cortisol were determined at induction of anesthesia, at the end of surgery, and 1
      h after surgery. RESULTS: No infants in the three groups had hypoglycemia (< 50
      mg.dl-1) throughout the study. In the LR group, plasma glucose concentration
      remained unchanged perioperatively compared with the basal values (at induction),
      whereas in the D2LR group, it increased during surgery but remained
      normoglycemic. In the D5LR group, plasma glucose concentration increased markedly
      both during and after surgery. In 6 of 20 infants, plasma glucose was greater
      than 200 mg.dl-1 at the end of surgery. In 8 of 20 infants receiving glucose-free
      infusion, plasma glucose concentrations decreased at the end of surgery. In
      contrast, the plasma glucose concentration increased in infants receiving glucose
      infusion. In the LR group, plasma concentrations of nonesterified fatty acids and
      ketone bodies increased at the end of and after surgery, suggesting lipid
      mobilization. The base excess decreased in the LR groups as concentration of the
      ketone bodies increased. Plasma insulin concentrations increased in the D2LR and
      D5LR groups and decreased after surgery in infants receiving a glucose-free
      solution. No intergroup differences in plasma cortisol concentrations existed at
      any sample point. CONCLUSIONS: These data indicate that, in otherwise healthy
      infants undergoing minor surgery, intravenous infusion of 2% glucose may be
      sufficient to maintain plasma glucose concentrations within physiologic ranges
      and to prevent a compensatory increase in lipid mobilization (lipolysis) when
      fluids are infused at a rate of 6 ml.kg-1.h-1. However, there are limitations in
      extrapolating the results to neonates.

PMID- 7631947
TI  - Preanesthetic medication of children with midazolam using the Biojector jet
      injector.
AB  - BACKGROUND: A rapid, dependable, and economical technique to atraumatically
      sedate children before anesthesia that does not prolong postanesthesia care unit
      time remains elusive. The Biojector jet injection system uses carbon dioxide
      rather than a needle to deliver an intramuscular injection. The dose-response
      relationship when midazolam is administered was studied using this jet injector.
      METHODS: Forty children (2.3 +/- 1.3 yr old) undergoing elective myringotomy and
      tube placement were randomly assigned to receive 0.05, 0.1, 0.15, 0.2, or 0.3
      mg.kg-1 midazolam injected intramuscularly using the Biojector disposable syringe
      (0.006-inch orifice). Assessment of each child before, during, and 10 min after
      injection, on application of the anesthesia face mask, and every 15 min for 1 h
      after arrival to the postanesthesia care unit was made by an observer blinded to
      drug dosage. RESULTS: Face mask tolerance using doses > or = 0.1 mg.kg-1
      midazolam was acceptable and statistically different from 0.05 mg/kg. Crying on
      injection tended to increase with increasing dose. All children were awake and
      arousable, meeting discharge criteria, after 30 min from arrival in the
      postanesthesia care unit. CONCLUSIONS: Midazolam (0.1-0.15 mg.kg-1) administered
      using jet injection effectively and rapidly produces sedation, in a manner
      acceptable to parents, without delaying postanesthesia care unit discharge.

PMID- 7631948
TI  - Improved amplitude of myogenic motor evoked responses after paired transcranial
      electrical stimulation during sufentanil/nitrous oxide anesthesia.
AB  - BACKGROUND: Measurement of motor evoked responses to transcranial stimulation (tc
      MER) is a technique for intraoperative monitoring of motor pathways in the brain
      and spinal cord. However, clinical application of tc-MER monitoring is hampered
      because most anesthetic techniques severely depress the amplitude of motor evoked
      responses. Because paired electrical stimuli increase tc-MER responses in awake
      subjects, we examined their effects in anesthetized patients undergoing surgery.
      METHODS. Eleven patients whose neurologic condition was normal and who were
      undergoing spinal or aortic surgery were anesthetized with sufentanil-N20
      ketamine. Partial neuromuscular blockade (single-twitch height 25% of baseline)
      was maintained with vecuronium. Single and paired electrical stimuli were
      delivered to the scalp, and compound action potentials were recorded from the
      tibialis anterior muscle. The amplitude and latency of the tc-MERs were measured
      as the interval between paired stimuli was varied between 0 (single stimulus) and
      10 ms. All recordings were completed before spinal manipulation or aortic
      clamping. RESULTS: Median amplitude of the tc-MER after a single stimulus was 106
      microV (10th-90th percentiles: 23-1,042 microV), and the latency to onset was
      33.2 +/- 1.4 ms (SD). With paired stimuli (interstimulus interval 2-3 ms), tc-MER
      amplitudes increased to 285 (79-1,605) microV, or 269% of the single-pulse
      response (P < 0.01). Reproducibility of individual responses increased with
      paired stimulation. Onset latency decreased to 31.4 +/- 3.2 ms (P < 0.05).
      Maximum amplitude augmentation was observed with interstimulus intervals between
      2 and 5 ms and in patients with low-amplitude responses after single-pulse
      stimulation. CONCLUSIONS: Application of paired transcranial electrical stimuli
      increases amplitudes and reproducibility of tc-MERs during anesthetic-induced
      depression of the motor system. The effect may represent temporal summation of
      stimulation at cortical or spinal sites. The results of this study warrant
      further clinical evaluation of paired transcranial stimulation.

PMID- 7631950
TI  - Automated echocardiographic analysis. Examination of serial intraoperative
      measurements.
AB  - BACKGROUND: Although transesophageal echocardiography allows continuous
      intraoperative cardiac monitoring, the technique has been limited by the lack of
      a method for realtime, quantitative assessment of cardiac chamber size and
      systolic function. Automated border detection (ABD), based on an analysis of
      integrated backscatter, is a new technique that is purported to provide real
      time, quantitative assessment of left ventricular (LV) areas and fractional area
      change (FAC). A prospective investigation was designed to assess the accuracy and
      trending capability of ABD during continuous intraoperative monitoring. METHODS:
      In 16 patients monitored throughout noncardiac surgical procedures, serial real
      time estimates of LV end-diastolic area (EDA), end-systolic area (ESA), and FAC
      by ABD were compared with paired off-line manual measurements made by two
      experiences echocardiographers. RESULTS: There was a high correlation between
      real-time ABD estimates of LV ESA (r = 0.93), EDA (r = 0.89), and FAC (r = 0.90)
      to those of the off-line technique. The automated technique systematically
      underestimated both EDA and ESA, resulting in a small underestimation of FAC. The
      automated technique demonstrated an accuracy rate of 96% in tracking serial
      changes in LV area. The technique performed with an 83% sensitivity and 85%
      specificity for detecting acute changes in LV area. CONCLUSIONS: This analysis of
      serial intraoperative echocardiograms demonstrates the accuracy of ABD to
      estimate LV area in real time and to track serial changes in cardiac area during
      surgery. Although ABD is an automated technique, application by personnel
      experienced in its operation and an echocardiographic system that includes
      lateral-gain adjustment controls are recommended for its optimal performance.

PMID- 7631949
TI  - Pharmacokinetics of inhaled liposome-encapsulated fentanyl.
AB  - BACKGROUND: Pulmonary administration of fentanyl solution can provide
      satisfactory but brief postoperative pain relief. Liposomes are microscopic
      phospholipid vesicles that can entrap drug molecules. Liposomal delivery of
      fentanyl has the potential to control the uptake of fentanyl by the lungs and
      thus provide sustained drug release. To demonstrate that inhalation of a mixture
      of free and liposome-encapsulated fentanyl can provide a rapid increase and
      sustained plasma fentanyl concentrations (CfenS), this study determined the
      pharmacokinetic profiles after the inhalation of free and liposome-encapsulated
      fentanyl in healthy volunteers. METHODS: After obtaining institutional approval
      and informed consent, ten healthy volunteers (five men, five women) were studied.
      Each subject received 200 micrograms intravenous fentanyl and inhaled 2,000
      micrograms of free (50%) and liposome-encapsulated fentanyl (50%) on separate
      occasions. Frequent venous blood samples were collected, and CfenS were
      determined by radioimmunoassay. The pharmacokinetics and absorption
      characteristics of the inhaled mixture of free and liposome-encapsulated fentanyl
      were determined using moment analysis and least-squares numeric deconvolution.
      RESULTS: The mean (+/- SD) volume of distribution at steady-state and clearance
      of fentanyl after the intravenous administration were comparable to previous
      studies: 435 +/- 1821 and 0.584 +/- 0.209 l.min-1, respectively. The mean (+/-
      SD) peak Cfen was significantly greater for the intravenous administration
      compared to the aerosol mixture of free and liposome-encapsulated fentanyl (4.67
      +/- 1.87 vs. 1.15 +/- 0.36 ng.ml-1). However, CfenS at 8 and 24 h after aerosol
      administration were greater compared to intravenous (0.25 +/- 0.14 and 0.12 +/-
      0.16 ng.ml-1 for aerosol versus 0.16 +/- 0.10 and 0.05 +/- 0.06 ng.ml-1 for
      intravenous). The peak absorption rate, time to peak absorption, and
      bioavailability after inhalation were 7.02 (+/- 2.34) micrograms.min, -1(16) (+/-
      8.0) min, and 0.12 (+/- 0.11), respectively. CONCLUSIONS: The data suggest that
      this analgesic method offers a simple and noninvasive route of administration
      with a rapid increase of Cfen and a prolonged therapeutic fentanyl concentration.
      Future studies are required to determine the optimal liposome composition that
      would produce a sustained stable Cfen within analgesic therapeutic
      concentrations.

PMID- 7631952
TI  - Placental transfer and neonatal effects of epidural sufentanil and fentanyl
      administered with bupivacaine during labor.
AB  - BACKGROUND: This randomized double-blind investigation was designed to study the
      placental transfer and neonatal effects of epidural sufentanil and fentanyl
      infused with bupivacaine for labor analgesia. METHODS: Healthy parturient women
      (n = 36) received epidural bupivacaine alone (group B) or with fentanyl (group B
      F) or sufentanil (group B-S). Group B received a 12-ml bolus of 0.25% bupivacaine
      followed by a 10 ml/h infusion of 0.125% bupivacaine. Groups B-F and B-S received
      a 12-ml bolus of 0.125% bupivacaine with 75 micrograms fentanyl or 15 micrograms
      sufentanil, respectively, followed by 10 ml/h of 0.125% bupivacaine with fentanyl
      1.5 micrograms/ml or sufentanil 0.25 micrograms/ml. Maternal venous (MV) and
      umbilical arterial (UA) and umbilical venous (UV) bupivacaine and opioid plasma
      concentrations were determined. Neonatal assessment included Apgar scores,
      umbilical cord blood gas analyses, and neurobehavioral testing at delivery and at
      2 and 24 h of life using the Neurologic and Adaptive Capacity Score (NACS).
      RESULTS: The mean total dose of fentanyl was 136.6 +/- 13.1 micrograms (SEM), and
      of sufentanil, 23.8 +/- 1.8 micrograms. Although administered in a ratio of
      5.7:1, fentanyl and sufentanil MV plasma concentrations were in the ratio of
      27:1. UV/MV ratios were 0.37 for fentanyl and 0.81 for sufentanil. Fentanyl was
      detected in most UA samples, whereas sufentanil was present in only one sample.
      Neonatal condition was good and generally similar in all groups, with the
      exception of a lower NACS at 24 h in group B-F. CONCLUSIONS: Although the degree
      of placental transfer of sufentanil appeared greater than that of fentanyl, lower
      MV sufentanil concentrations resulted in less fetal exposure to sufentanil. The
      lower NACS at 24 h in group B-F may reflect the continued presence of fentanyl in
      the neonate.

PMID- 7631951
TI  - Alfentanil slightly increases the sweating threshold and markedly reduces the
      vasoconstriction and shivering thresholds.
AB  - BACKGROUND: Hypothermia is common in surgical patients and victims of major
      trauma; it also results from environmental exposure and drug abuse. In most
      cases, hypothermia results largely from drug-induced inhibition of normal
      thermoregulatory control. Although opioids are given to a variety of patients,
      the thermoregulatory effects of opioids in humans remain unknown. Accordingly,
      the hypothesis that opioid administration impairs thermoregulatory control was
      tested. METHODS: Eight volunteers were studied, each on 3 days: (1) a target
      total plasma alfentanil concentration of 100 ng/ml, (2) control (no drug), and
      (3) a target alfentanil concentration of 300 ng/ml. Each day, skin and core
      temperatures were increased sufficiently to provoke sweating. Temperatures
      subsequently were reduced to elicit peripheral vasoconstriction and shivering.
      Mathematical compensations were made for changes in skin temperature using the
      established linear cutaneous contributions to control of sweating (10%) and to
      vasoconstriction and shivering (20%). From the calculated thresholds (core
      temperatures triggering responses at a designated skin temperature of 34 degrees
      C) and unbound plasma alfentanil concentrations, the individual concentration
      response relationship was determined. The concentration-response relationship for
      all the volunteers was determined similarly using total alfentanil
      concentrations. RESULTS: In terms of unbound concentration, alfentanil increased
      the sweating threshold (slope = 0.021 +/- 0.016 degrees C.ng-1.ml; r2 = 0.92 +/-
      0.06). Alfentanil also significantly decreased the vasoconstriction (slope = 
      0.075 +/- 0.067 degrees C.ng-1.ml; r2 = 0.92 +/- 0.07) and shivering thresholds
      (slope = -0.063 +/- -0.037 degrees C.ng-1.ml; r2 = 0.98 +/- 0.04). In terms of
      total alfentanil concentration (degrees C.ng-1.ml), the sweating threshold
      increased according to the equation: threshold (degrees C) = 0.0014[alfentanil] +
      37.2 (r2 = 0.33). In contrast, alfentanil produced a linear decrease in the core
      temperature, triggering vasoconstriction: threshold (degrees C) = 
      0.0049[alfentanil] + 36.7 (r2 = 0.64). Similarly, alfentanil linearly decreased
      the shivering threshold: threshold (degrees C) = -0.0057[alfentanil] + 35.9 (r2 =
      0.70). CONCLUSIONS: The observed pattern of thermoregulatory impairment is
      similar to that produced by most general anesthetics: a slight increase in the
      sweating threshold and a substantial, linear decrease in the vasoconstriction and
      shivering thresholds.

PMID- 7631953
TI  - d-Tubocurarine accentuates the burn-induced upregulation of nicotinic
      acetylcholine receptors at the muscle membrane.
AB  - BACKGROUND: Increases in acetylcholine receptors (AChRs) at the muscle membrane,
      induced by burn injury, have been associated with a hyperkalemic response to
      succinylcholine and resistance to d-tubocurarine-like drugs. Muscle relaxants
      often are administered to burn-injured patients in the intensive care unit to
      facilitate mechanical ventilation. This study in rats tested whether continuous
      administration of d-tubocurarine in subparalytic doses exaggerates the
      upregulation of AChRs induced by burn trauma. Subparalytic doses were used to
      avoid the confounding effects of immobilization. METHODS: Three days after an
      approximate 50% body surface area burn or sham injury, the animals received an
      infusion of 3.03 +/- 0.05 micrograms/h of d-tubocurarine or equal volume of
      saline directly to the left gastrocnemius muscle via catheter connected to a
      subcutaneously implanted osmotic pump. After 7 days of d-tubocurarine or saline
      infusion, the AChRs were quantitated using 125I-alpha-bungarotoxin. The AChRs on
      the d-tubocurarine or saline-infused left gastrocnemius were compared to the
      contralateral gastrocnemius in the same group. The right or left gastrocnemius
      AChRs were compared to the ipsilateral muscles between groups. These intra- and
      intergroup comparisons allowed the delineation of the effects of catheter
      irritation, burns, or d-tubocurarine on AChRs. RESULTS: Daily examination of the
      withdrawal response to toe-pinch revealed no evidence of paralysis. Weight loss
      in the burn-injury animals receiving d-tubocurarine or saline was similar,
      confirming that the infusion of d-tubocurarine did not impair the mobility of the
      animals to move and feed. The plasma d-tubocurarine concentration after 7 days of
      infusion was 26.0 +/- 12 ng/ml (mean +/- SE). Regardless of burn or sham injury
      or of d-tubocurarine or saline infusion, the concentration of AChRs on the left
      was consistently greater than in the contralateral right gastrocnemius muscles
      within the same group, indicating that manipulation of the area alone can result
      in upregulation of AChRs. The AChRs in the right gastrocnemius of burn-injured
      animals were greater than those in the same muscle of sham-injured animals,
      regardless of saline (7.24 +/- 0.9 vs. 5.7 +/- 0.5 fmoles/mg protein, P = 0.06)
      or d-tubocurarine (7.3 +/- 0.4 vs. 5.7 +/- 0.5, P < 0.05) infusion to the burn
      injury groups. AChRs in the left gastrocnemius of burn-injury animals receiving d
      tubocurarine were significantly greater than those in burn- or sham-injury
      animals receiving saline (13.9 +/- 1.1 vs. 9.8 +/- 1.2 and 7.1 +/- 0.5 fmoles/mg
      protein, respectively, P < 0.05). CONCLUSIONS: Burn-induced upregulation of AChRs
      is accentuated by infusion of subparalytic doses of d-tubocurarine. Concomitant
      administration of d-tubocurarine to burn-injured patients may result in further
      exaggeration of the aberrant responses to neuromuscular relaxants.

PMID- 7631954
TI  - Binding of halothane to serum albumin demonstrated using tryptophan fluorescence.
AB  - BACKGROUND: The site of action of general anesthesia remains controversial, but
      evidence in favor of specific protein target(s) is accumulating. Saturable
      binding of halothane to bovine serum albumin (BSA) has recently been reported
      using photoaffinity labeling and fluorine 19 nuclear magnetic resonance
      spectroscopy. We report a new approach to study anesthetic binding to soluble
      proteins, based on native tryptophan fluorescence. METHODS: Thymol-free halothane
      and fatty acid-free BSA were equilibrated in gas-tight Hamilton syringes and
      dispensed into stoppered quartz cuvettes at predetermined dilutions. Steady-state
      fluorescence spectroscopy was used to study their interaction. RESULTS: Halothane
      quenched the tryptophan fluorescence of BSA in a concentration-dependent,
      saturable manner with a dissociation constant = 1.8 +/- 0.2 mM and a Hill number
      = 1.0 +/- 0.1. The two optical isomers of halothane bound to BSA with equal
      affinity. The ability of halothane to quench BSA tryptophan fluorescence was
      markedly decreased at pH 3.0 (which causes full uncoiling of BSA), with loss of
      saturable binding. Diethyl ether displaced a portion of halothane from its
      binding sites. Circular dichroism spectroscopy revealed no significant effect of
      halothane or diethyl ether on the secondary structure of BSA. CONCLUSIONS: The
      results suggest that halothane binds in hydrophobic domains containing tryptophan
      in BSA. This approach may prove useful for studying the interaction of volatile
      anesthetics and proteins and has the advantage that the location of halothane in
      the protein is identified.

PMID- 7631955
TI  - Temperature changes of > or = 1 degree C alter functional neurologic outcome and
      histopathology in a canine model of complete cerebral ischemia.
AB  - BACKGROUND: Changes in basal temperature of > or = 1 degree C (e.g., fever
      induced hyperthermia or anesthesia-related hypothermia) are a common occurrence
      in neurologically impaired patients. The current study tested the hypothesis that
      temperature changes as small as 1 degree C or 2 degrees C would significantly
      alter post-ischemic functional neurologic outcome and cerebral histopathology.
      The hypothesis was tested in a canine model of transient, complete cerebral
      ischemia. METHODS: After institutional approval, 21 dogs were randomly assigned
      to one of three temperature-specific groups: (1) a reference group maintained at
      37.0 +/- 0.3 degree C (target temperature +/- range); (2) a 38.0 +/- 0.3 degree C
      group; or (3) a 39.0 +/- 0.3 degree C group (n = 7 per group). Complete cerebral
      ischemia 12.5 min in duration was produced using an established model of arterial
      hypotension plus intracranial hypertension. Right atrial and cranial (beneath the
      temporalis muscles) temperatures were maintained at the target value, beginning
      20 min before ischemia and ceasing 1 h postischemia. Thereafter, temperatures
      were returned to 37.0 +/- 0.3 degree C in all dogs. After discharge from the
      intensive care environment, all dogs were placed in a temperature-controlled
      recovery area. Neurologic assessment was performed by a blinded observer at 24,
      48, and 72 h postischemia using a 100-point scoring scale. After the 72 h
      examination (with the dogs anesthetized) or at the time of ischemia-related
      death, the brains were excised and preserved. The brains subsequently were
      histologically scored by a neuropathologist who was unaware of the treatment
      groups. All 21 dogs were included in the analysis of neurologic function;
      however, only dogs that survived for > or = 24 h postischemia were included in
      the histopathology analysis. RESULTS: Dogs were well matched for systemic
      physiologic variables throughout the study, with the exception of temperature.
      During the 72 h postischemic examination, dogs maintained at 37 degrees C were
      either normal or near normal. In contrast, dogs maintained at 39 degrees C were
      either comatose or died from ischemia-related causes. Dogs maintained at 38
      degrees C were intermediate between 37 degrees C and 39 degrees C dogs. When
      compared with the reference group, both 38 degrees C and 39 degrees C dogs had
      significantly worse neurologic function scores (P < 0.01 and < 0.001,
      respectively) and histopathology scores (P < 0.01 for both). There also was a
      significant correlation between neurologic function and histopathology rank
      scores (rs = 0.96; P < 0.001). CONCLUSIONS: Small, clinically relevant changes in
      temperature (1 degree C or 2 degrees C) resulted in significant alterations in
      both postischemic neurologic function and cerebral histopathology. Assuming that
      our results are transferable to humans, the results suggest that, in patients at
      imminent risk for ischemic neurologic injury, body temperature should be closely
      monitored. Further, the clinician should aggressively treat all episodes of
      hyperthermia until the patient is no longer at risk for ischemic neurologic
      injury.

PMID- 7631956
TI  - Contrasting actions of intrathecal U50,488H, morphine, or [D-Pen2, D-Pen5]
      enkephalin or intravenous U50,488H on the visceromotor response to colorectal
      distension in the rat.
AB  - BACKGROUND: Visceral sensations are an important component of many clinical pain
      states. It is apparent that intrathecal pain relief may be more effective if
      appropriate combinations of drugs rather than a single agent can be used. The
      purpose of this study was to examine the relative contribution of opioid receptor
      subtypes to visceral antinociception using colorectal distension as a visceral
      pain model. METHODS: The minimum colorectal distending pressure necessary to
      evoke a visceromotor response (contraction of abdominal musculature) was
      determined before and after the administration of opioid agonists for the mu
      (morphine), delta ([D-Pen2, D-Pen5] enkephalin [DPDPE]), and kappa (U50,488H)
      opioid receptors. In addition to the three drugs administered intrathecally, U50,
      488H was also administered intravenously. RESULTS: Morphine and DPDPE produced a
      reversible increase in threshold for activation of the visceromotor response (50%
      maximum possible effect [MPE] at intrathecal doses of 2.2 and 16.4 micrograms,
      respectively). The maximum intrathecal dose of U50,488H (100 micrograms) produced
      only a 20% MPE. Intravenous U50,488H produced a 50% MPE at a dose of 2.6 mg/kg.
      CONCLUSIONS: The results suggest that spinal mu- and delta- but not kappa-opioid
      receptors have a significant role in the modulation of visceral nociception
      induced by colorectal distension. In addition, the results indicate that
      activation of nonspinal kappa receptors may mediate visceral antinociception.

PMID- 7631958
TI  - Interaction of halothane with inhibitory G-proteins in the human myocardium.
AB  - BACKGROUND: Halothane has been reported to possess a catecholamine-sensitizing
      effect in laboratory animals and in anesthetized patients and to enhance the
      positive inotropic effect of isoproterenol in human papillary muscle strips. The
      current study was designed to investigate further the underlying subcellular
      mechanisms on human myocardium, in particular the mechanism of action of
      halothane on G-proteins. METHODS: To investigate the effect of halothane on
      adenylyl cyclase activity, isoproterenol-, guanylylimidodiphosphate (Gpp(NH)p)-,
      and forskolin-activated enzyme activities were studied alone and in the presence
      of halothane in native and manganese-treated membranes. The mechanisms of
      halothane interaction with inhibitory G-proteins (G1) were studied in adenosine
      diphosphate-ribosylation studies with pertussis toxin and immunochemical
      techniques. RESULTS: Halothane (1%) augmented isoproterenol- and Gpp(NH)p
      stimulated adenylyl cyclase activity but had no effect on forskolin-stimulated
      enzyme activity. Manganese ions inhibited the stimulating effect of isoproterenol
      and Gpp(NH)p on adenylyl cyclase activity, but the effect of forskolin remained
      unchanged in control and halothane-treated membranes. In the presence of
      pertussis toxin, the effect of isoproterenol and Gpp(NH)p on adenylyl cyclase
      activity was enhanced, but further stimulation by halothane was abolished.
      Halothane did not influence the attachment of Gi alpha to the membrane. No effect
      of halothane on adenosine diphosphate-ribosylation of Gi alpha by pertussis toxin
      was observed. CONCLUSIONS: Halothane stimulates adenylyl cyclase activity by
      inhibiting the function of the inhibitory G-proteins by interfering with the
      effects of the alpha subunits or beta gamma subunits with the effector. Decreased
      membrane attachment of Gi alpha in the presence of halothane does not occur. The
      interaction of alpha and beta gamma subunits is not affected by halothane.
      Halothane does not impair the binding of pertussis toxin to the Gi alpha-protein.

PMID- 7631957
TI  - Visceral antinociceptive effects of spinal clonidine combined with morphine, [D
      Pen2, D-Pen5] enkephalin, or U50,488H.
AB  - BACKGROUND: Visceral pain is an important component of many clinical pain states.
      The perispinal administration of drug combinations rather than a single agent may
      reduce side effects while maximizing analgesic effectiveness. The purpose of this
      study was to examine the nature of interactions between an alpha 2-adrenergic
      agonist (clonidine) and a mu-opioid agonist (morphine), a delta-opioid agonist
      ([D-Pen2, D-Pen5] enkephalin [DPDPE]), or a kappa-opioid agonist (U50,488H).
      METHODS: Colorectal distension was used to elicit a nociceptive visceromotor
      response (contraction of abdominal musculature) in rats. The ability of
      intrathecally administered clonidine alone or in combination with morphine,
      DPDPE, or U50,488H to alter thresholds for the production of the visceromotor
      response was examined. RESULTS: Clonidine produced dose-dependent reduction in
      threshold. U50,488H, at the doses tested, showed no synergistic interaction with
      clonidine. CONCLUSIONS: Spinal combinations of alpha 2-adrenergic and mu- or
      delta- but not kappa-opioid agonists may be beneficial in the control of visceral
      pain.

PMID- 7631959
TI  - Differential effects of isoflurane and halothane on aortic input impedance
      quantified using a three-element Windkessel model.
AB  - BACKGROUND: Systemic vascular resistance (the ratio of mean aortic pressure [AP]
      and mean aortic blood flow [AQ]) does not completely describe left ventricular
      (LV) afterload because of the phasic nature of pressure and blood flow. Aortic
      input impedance (Zin) is an established experimental description of LV afterload
      that incorporates the frequency-dependent characteristics and viscoelastic
      properties of the arterial system. Zin is most often interpreted through an
      analytical model known as the three-element Windkessel. This investigation
      examined the effects of isoflurane, halothane, and sodium nitroprusside (SNP) on
      Zin. Changes in Zin were quantified using three variables derived from the
      Windkessel: characteristic aortic impedance (Zc), total arterial compliance (C),
      and total arterial resistance (R). METHODS: Sixteen experiments were conducted in
      eight dogs chronically instrumented for measurement of AP, LV pressure, maximum
      rate of change in left ventricular pressure, subendocardial segment length, and
      AQ. AP and AQ waveforms were recorded in the conscious state and after 30 min
      equilibration at 1.25, 1.5, and 1.75 minimum alveolar concentration (MAC)
      isoflurane and halothane. Zin spectra were obtained by power spectral analysis of
      AP and AQ waveforms and corrected for the phase responses of the transducers. Zc
      and R were calculated as the mean of Zin between 2 and 15 Hz and the difference
      between Zin at zero frequency and Zc, respectively. C was determined using the
      formula C = (Ad.MAP).[MAQ.(Pes-Ped)]-1, where Ad = diastolic AP area; MAP and MAQ
      = mean AP and mean AQ, respectively; and Pes and Ped = end-systolic and end
      diastolic AP, respectively. Parameters describing the net site and magnitude of
      arterial wave reflection were also calculated from Zin. Eight additional dogs
      were studied in the conscious state before and after 15 min equilibration at
      three equihypotensive infusions of SNP. RESULTS: Isoflurane decreased R (3,205 +/
      315 during control to 2,340 +/- 2.19 dyn.s.cm-5 during 1.75 MAC) and increased
      C(0.55 +/- 0.02 during control to 0.73 +/- 0.06 ml.mmHg-1 during 1.75 MAC) in a
      dose-related manner. Isoflurane also increased Zc at the highest dose. Halothane
      increased C and Zc but did not change R. Equihypotensive doses of SNP decreased R
      and produced marked increases in C without changing Zc. No changes in the net
      site or the magnitude of arterial wave reflection were observed with isoflurane
      and halothane, in contrast to the findings with SNP. CONCLUSIONS: The major
      difference between the effects of isoflurane and halothane on LV afterload
      derived from the Windkessel model of Zin was related to R, a property of
      arteriolar resistance vessels, and not to Zc or C, the mechanical characteristics
      of the aorta. No changes in arterial wave reflection patterns determined from Zin
      spectra occurred with isoflurane and halothane. These results indicate that
      isoflurane and halothane have no effect on frequency-dependent arterial
      properties.

PMID- 7631960
TI  - Inhibitory effect of lidocaine on cultured porcine aortic endothelial cell
      dependent antiaggregation of platelets.
AB  - BACKGROUND: Vascular spasm is a well-known complication during vascular surgery.
      Topical lidocaine is frequently used to prevent this spasm. However, the effects
      of lidocaine on the endothelium-dependent antiaggregation are not clear. METHODS:
      The aggregation of platelet-rich plasma (PRP) obtained from healthy volunteers
      was measured by the turbidimetric technique at 37 degrees C. (1) Cultured porcine
      aortic endothelial cells were preincubated with lidocaine (3.7 microM to 37 mM),
      NG-methyl-L-arginine (300 microM), or indomethacin (10 microM) for 30 min. The
      preincubation medium was exchanged with a medium containing +/- 1 microM
      bradykinin for 1-min stimulation of endothelial cells. One hundred microliters of
      the supernatant was then added to PRP (750 micro1) just after stimulation of PRP
      with collagen (4 micrograms/ml). (2) Authentic nitric oxide (NO) or prostacyclin
      (PGI2) was applied to collagen-stimulated PRP with or without lidocaine (100
      micrograms/ml). RESULTS: (1) The supernatant from endothelial cells without
      bradykinin stimulation showed "basal" antiaggregation (13.8 +/- 3.2%; n = 6).
      Bradykinin enhanced the antiaggregation (100 +/- 0%; n = 6). NG-methyl-L-arginine
      or indomethacin (antagonists of NO or PGI2) inhibited the bradykinin-evoked
      antiaggregation (10.3 +/- 2.1% and 13.6 +/- 3.7%, respectively; n = 6).
      Simultaneous preincubation of both agents completely blocked the effect (-4.2 +/-
      2.8%; n = 6). Lidocaine failed to influence basal antiaggregation, but it
      inhibited bradykinin-stimulated antiaggregation in a concentration-dependent
      manner (concentration causing 50% inhibition = 108 +/- 41 microM; n = 6). (2) In
      contrast, lidocaine did not shift the 50% effective concentration of NO (control,
      1.3 +/- 0.1 microM vs. lidocaine, 1.6 +/- 0.1 microM) or PGI2 (control, 405 +/-
      54 nM vs. lidocaine, 257 +/- 41 nM) for antiaggregation. CONCLUSIONS: Our results
      suggest that lidocaine has an inhibitory effect on antiaggregation derived from
      endothelial cells, caused by the inhibition of NO and PGI2 released from
      endothelial cells.

PMID- 7631962
TI  - Halothane, enflurane, and isoflurane do not affect the basal or agonist
      stimulated activity of partially isolated soluble and particulate guanylyl
      cyclases of rat brain.
AB  - BACKGROUND: Evidence suggests that inhalational anesthetics interact with the
      nitric oxide-guanylyl cyclase signaling pathway in the central nervous system and
      that the inhibitation of this pathway in brain may result in an anesthetic,
      analgesic, or sedative effect. The mechanism of the effects inhalational
      anesthetics on this signaling pathway is not clear. This study attempted to
      determine whether inhalational anesthetics directly affect soluble or particulate
      guanylyl cyclase activity in a partially isolated enzyme system. METHODS: The
      effects of halothane (0.44-4.4%), enflurane (1.34-6.7%), and isoflurane (0.6
      5.0%) on basal or stimulated soluble or particulate guanylyl cyclase activity
      were examined. Soluble guanylyl cyclase was isolated from whole rat brain and was
      stimulated by sodium nitroprusside or nitric oxide. Particulate guanylyl cyclase
      was isolated from rat olfactory bulb and was stimulated by rat atrial natriuretic
      peptide(1-28). Cyclic guanosine monophosphate content was measured by
      radiommunoassay. The concentrations of anesthetics in the incubation solution
      were confirmed by gas chromatography methods. RESULTS: None of the three
      anesthetics affected the activity of basal or stimulated soluble or particulate
      guanylyl cyclase at the concentrations examined in the current experimental
      conditions. CONCLUSIONS: These results suggest that halothane, enflurane, and
      isoflurane do not directly interact with soluble or particulate guanylyl cyclases
      of rat brain.

PMID- 7631961
TI  - Frequency-dependent effects of propofol on atrioventricular nodal conduction in
      guinea pig isolated heart. Mechanism and potential antidysrhythmic properties.
AB  - BACKGROUND: The use of propofol has been associated with episodes of
      bradycardias. The mechanism(s) underlying these phenomena are not well defined.
      Therefore we investigated (1) the chronotropic and dromotropic effects of
      propofol, (2) the frequency-dependent effects of propofol on the atrioventricular
      (AV) node, and (3) the physiologic mechanism(s) underlying propofol's effects on
      AV nodal conduction. METHODS: Guinea pig isolated, perfused hearts were
      instrumented for measurement of atrial rate and AV nodal conduction time in
      spontaneously beating hearts, or stimulus-to-His bundle (S-H) intervals in
      atrially paced hearts. In addition, the Wenckebach cycle length, effective
      refractory period and S-H interval prolongation to an abrupt increase in pacing
      rate were measured to further define propofol's dromotropic effects and frequency
      dependent behavior. RESULTS: Propofol, in a concentration-dependent manner, (1)
      slowed atrial rate and AV nodal conduction time in spontaneously beating hearts,
      (2) prolonged the S-H interval in atrially paced hearts, and (3) prolonged
      Wenckebach cycle length and effective refractory period. The negative dromotropic
      effect of propofol was greater during atrial pacing than in spontaneously beating
      hearts. Furthermore, this effect was enhanced at faster pacing rates, indicating
      frequency-dependent behavior. Atropine significantly antagonized propofol-induced
      S-H interval prolongation. The results of competition binding studies also
      supported a M2-muscarinic receptor-mediated mechanism. CONCLUSIONS: We conclude
      that in the isolated guinea pig heart, propofol slows atrial rate and depresses
      AV nodal conduction in a concentration-dependent manner. The negative dromotropic
      effect of propofol shows frequency dependence and is predominantly mediated by M2
      muscarinic receptors. Given the marked rate dependence of propofol's AV nodal
      actions, this anesthetic agent may impart antidysrhythmic protection to those
      patients susceptible to supraventricular tachycardias.

PMID- 7631964
TI  - Time-limited certification. American Board of Anesthesiology.

PMID- 7631963
TI  - Theoretical analysis of cerebral venous blood hemoglobin oxygen saturation as an
      index of cerebral oxygenation during hypothermic cardiopulmonary bypass. A
      counterproposal to the "luxury perfusion" hypothesis.
AB  - BACKGROUND: Jugular venous catheters and near-infrared spectroscopy can measure
      cerebral venous blood hemoglobin oxygen saturation (SvO2). We used computer
      simulation to characterize the relation between Sv02 and cerebral metabolic rate
      for oxygen (CMR02) during hypothermic cardiopulmonary bypass (CPB). METHODS: We
      developed a theoretical model of cerebral oxygen consumption and blood-brain
      oxygen transfer. Our model included the temperature dependence of blood and brain
      oxygen solubility; the temperature, age, and acid-base dependence of hemoglobin
      oxygen dissociation; and the temperature and age dependence of CMRO2. We
      simulated cerebral blood flow reductions that decreased Sv02 and CMR02. RESULTS:
      Our model predicts the relation between CMR02 and Sv02 to be dependent on
      temperature, because of a shift of the oxygen partial pressure at which
      hemoglobin oxygen saturation equals 0.50. For example, during normothermic CPB,
      Sv02 can decrease to 30% before CMR02 will decrease to less than 90% of normal.
      In contrast, for alpha-stat management of infants at 17 degrees C, Sv02 must be
      maintained at greater than 95% to maintain CMR02 at greater than 90% of its
      temperature appropriate value. CONCLUSIONS: High Sv02 observed during hypothermic
      CPB may indicate impaired oxygen transfer from hemoglobin to brain, not "luxury
      perfusion." The relation between Sv02 and CMR02 depends dramatically on the
      temperature of the patient. Sv02 per se may not be reliable index of normal CMR02
      during hypothermic CPB.

PMID- 7631965
TI  - Difficult intubation assisted by three-dimensional computed tomography imaging of
      the pharynx and the larynx.

PMID- 7631966
TI  - The optimal breathing tube for tracheal resection and reconstruction.

PMID- 7631967
TI  - Successful use of laryngeal mask airway in low-weight expremature infants with
      bronchopulmonary dysplasia undergoing cryotherapy for retinopathy of the
      premature.

PMID- 7631968
TI  - The stellate ganglion in magnetic resonance imaging: a quantification of the
      anatomic variability.

PMID- 7631969
TI  - Laryngoscope handle contamination.

PMID- 7631970
TI  - Preoxygenation.

PMID- 7631972
TI  - Pediatric pain services: monitoring for epidural analgesia in the non-intensive
      care unit setting.

PMID- 7631971
TI  - Insertion of a lumbar drain using a pediatric central venous catheter guidewire.

PMID- 7631973
TI  - Patient-controlled analgesia and the acute pain service in the United States:
      Health-Care Financing Administration policy is impeding optimal patient
      controlled analgesia management.

PMID- 7631974
TI  - Pharyngeal packs can cause massive swelling of the tongue after neurosurgical
      procedures.

PMID- 7631975
TI  - Missing babies.

PMID- 7631976
TI  - International workshop on anesthetic mechanisms. Takamatsu, Japan, December 12
      14, 1994.

PMID- 7631977
TI  - Molecular/cell engineering approach to autocrine ligand control of cell function.
AB  - Tissue engineering, along with other modern cell- and tissue-based health care
      technologies, depends on successful regulation of cell function by molecular
      means, including pharmacological agents, materials, and genetics. This regulation
      is generally mediated by cell receptor/ligand interactions providing primary
      targets for molecular intervention. While regulatory ligands may often be
      exogenous in nature, in the categories of endocrine and paracrine hormone
      systems, they are being increasingly appreciated as crucial in local control of
      cell and tissue function. Improvements in design of health care technologies
      involving autocrine ligand interactions with cell receptors should benefit from
      increased qualitative and quantitative understanding of the kinetic and transport
      processes governing these interactions. In this symposium paper we offer a
      concise overview of our recent efforts combining molecular cell biology and
      engineering approaches to increase the understanding of how molecular and
      cellular parameters may be manipulated for improved control of cell and tissue
      function regulated by autocrine ligands.

PMID- 7631978
TI  - An endothelial cell-smooth muscle cell co-culture model for use in the
      investigation of flow effects on vascular biology.
AB  - Flow and the associated shear stress have been shown to play an active role in
      the regulation of the structure and function of endothelial cells (EC) in vitro.
      Although cultured EC subjected to flow exhibit an elongated morphology and a
      decreased cell growth rate rather like those observed in vivo, there are
      differences in morphology and growth rate, as well as other characteristics,
      between in vitro and in vivo EC. This suggests that flow is only one of the many
      factors affecting EC differentiation in vivo. In this study, a co-culture model
      system was designed, which includes smooth muscle cells (SMC), a matrix of
      collagen type I, and a confluent monolayer of EC, and this simplified model of
      the arterial wall was subjected to a steady, laminar shear stress of 10 and 30
      dyn/cm2. Under non-flow conditions, EC exhibited an elongated shape, but with a
      random orientation. In response to flow, there was an alignment with the
      direction of flow. This alignment occurred more rapidly at 30 dyn/cm2 than at 10
      dyn/cm2. The collagen matrix was found to be primordial in the maintenance of a
      quiescent endothelium, even in the absence of SMC and flow, suggesting the
      importance of an organized extracellular matrix (ECM) in the differentiation of
      cells in vivo.

PMID- 7631979
TI  - Biomechanics of skeletal muscle capillaries: hemodynamic resistance, endothelial
      distensibility, and pseudopod formation.
AB  - The objective of this study was to investigate the structure of capillaries in
      rat skeletal muscle and their mechanical properties over a wide range of
      transmural pressures. Capillaries were fixed at controlled pressures and studied
      with intravital and electron microscopy. Capillary lumen dimensions depend on the
      local transmural pressure, with irregular and partially collapsed cross-sections
      at low transmural pressures and circular cross-sections at elevated pressures.
      The average circumferential wall stress is a nonlinear function of the
      circumferential stretch. Elevation of the transcapillary pressure serves to
      increase the endothelial surface area exposed to the lumen and to the basement
      membrane while the average endothelial thickness and cell volume decrease. The
      number of vesicles in the endothelium and their average size decrease with the
      stretching of the endothelial cell. The balance of membrane area measurements on
      the vesicles and on the cell surface show that the total membrane surface is
      conserved at all pressures, and the vesicles become unfolded during stretching of
      the endothelial cells. This suggests that the vesicle membrane serves as a
      reservoir for the increase of endothelial surface membrane area during capillary
      distension. Under normal or elevated capillary pressure, virtually no evidence
      for pseudopod formation by the endothelial cells was detected. If the capillary
      transmural pressure was reduced to zero in the presence of autologous plasma for
      periods of about 10 min, limited evidence for pseudopods in less than 10% of the
      capillary sections was seen. If the muscle capillaries were perfused with
      plasmalyte and fixed at low pressures, all capillaries exhibited pseudopod
      formation. Addition of plasma proteins prevented most pseudopod formations.
      Endothelial pseudopods are depleted of vesicles and form sheet-like projections.
      Once pseudopods are formed at low pressure, they cannot readily be unfolded by
      elevation of the capillary transmural pressure. Pseudopods appear to consist of a
      crosslinked actin matrix and may have a strong effect on the resistance to blood
      flow in capillaries. These results may be relevant with respect to capillary
      blood flow at low pressures.

PMID- 7631980
TI  - Stochasticity in membrane-localized "ligand-receptor-G protein" binding:
      consequences for leukocyte movement behavior.
AB  - The signal that governs the chemotactic response of mammalian white blood cells
      and tissue cells arises from membrane-localized binding events involving
      chemotactic factor ligands and receptors and G proteins. Fluctuations in this
      signal have been traditionally attributed to significant "noise" in receptor
      ligand binding owing to a limited number of receptors. This paper examines the
      validity and consequences of a new hypothesis which states that the noise could
      be associated with a limited number of G proteins as well as receptors. This work
      characterizes via stochastic analysis and simulation the effects of the relative
      sizes of G protein and receptor populations on the variance of fluctuations of
      receptor states and consequently on the directional persistence behavior of cells
      in uniform chemotactic factor concentrations under the assumptions of the model
      used to link a G protein-mediated receptor signal to cell turning. Our results
      suggest that there may exist an optimal number of G proteins through which
      chemotactic receptors can signal that maximizes cell orientation accuracy in a
      chemotactic factor gradient.

PMID- 7631981
TI  - Time series characterization of simulated microtubule dynamics in the nerve
      growth cone.
AB  - The process of neurite outgrowth is critically dependent on proper microtubule
      assembly. However, characterizing the dynamics of microtubule assembly and their
      quantitative relationship to neurite outgrowth is a difficult task. The
      difficulty can be reduced by using time series analysis which has broad
      application in characterizing the dynamics of stochastic, or "noisy," behaviors.
      Here we apply time series analysis to quantitatively compare simulated
      microtubule assembly and neurite outgrowth in vitro. Microtubule length life
      histories were simulated assuming constant growth and shrinkage rates coupled
      with random selection of growth and shrinkage times, a formulation based on the
      dynamic instability model of microtubule assembly. Net length displacements of
      simulated microtubules were calculated at discrete, evenly spaced times, and the
      resulting time series were characterized by both spectral and autocorrelation
      analysis. Depending on the sampling rate and the dynamic parameters, simulated
      microtubules exhibited significant autocorrelation and periodicity. To make a
      comparison to neurite outgrowth, we characterized the dynamic behavior of
      simulated microtubule populations and found it was not significantly different
      from that of single microtubules. The net displacements of rat superior cervical
      ganglion neurite tips were measured and characterized using time series methods.
      Their behavior was consistent with the microtubule dynamics for appropriate
      simulation parameters and sampling rates. Our results show that time series
      analysis can provide a useful tool for quantitative characterization of
      microtubule dynamics and neurite outgrowth and for assessing the relationship
      between them.

PMID- 7631982
TI  - Lysolipid exchange with lipid vesicle membranes.
AB  - While the aqueous solubility for bilayer phospholipids is less than 10(-10) M-
      keeping lipid membranes at essentially constant mass, single chain surfactants
      can have a significant aqueous solubility. Thus, in surfactant solutions, both
      monomer and micelles can interact with a lipid bilayer, and the mass and
      composition of the bilayer can be changed in seconds. These changes in
      composition are expected to have direct consequences on bilayer structure and
      material properties. We have found that the exchange of surfactants like
      lysolecithin can be described in terms of a kinetic model in which monomer and
      micelles are transported to the membrane from bulk solution. Molecular transport
      is considered at the membrane interfaces and across the midplane between the two
      monolayers of the bilayer. Using micropipet manipulation, single vesicles were
      transferred into lysolecithin solutions, and the measurement of vesicle area
      change gave a direct measure of lysolecithin uptake. Transfer back to
      lysolecithin-free media resulted in desorption. The rates of uptake and
      desorption could therefore be measured at controlled levels of membrane stress.
      With increasing lysolecithin concentration in the bulk phase, the amount of
      lysolecithin in the membrane reached saturation at approximately 3 mol% for
      concentrations below the critical micelle concentration (CMC) and at > 30 mol%
      for concentrations above the CMC. When convective transport was used to deliver
      lysolecithin, uptake occurred via a double exponential: initial uptake into the
      outer monolayer was fast (approximately 0.2 sec-1); transfer across the bilayer
      midplane was much slower (0.0019 sec-1).

PMID- 7631983
TI  - Monte Carlo simulations of membrane signal transduction events: effect of
      receptor blockers on G-protein activation.
AB  - Cells have evolved elaborate strategies for sensing, responding to, and
      interacting with their environment. In many systems, interaction of cell surface
      receptors with extracellular ligand can activate cellular signal transduction
      pathways leading to G-protein activation and calcium mobilization. In BC3H1
      smooth muscle-like cells, we find that the speed of calcium mobilization as well
      as the fraction of cells which mobilize calcium following phenylephrine
      stimulation is dependent upon receptor occupation. To determine whether receptor
      inactivation affects calcium mobilization, we use the receptor antagonist
      prazosin to block a fraction of cell surface receptors prior to phenylephrine
      stimulation. For cases of equal receptor occupation by agonist, cells with
      inactivated or blocked receptors show diminished calcium mobilization following
      phenylephrine stimulation as compared to cells without inactivated receptors.
      Ligand/receptor binding and two-dimensional diffusion of receptors and G-proteins
      in the cell membrane are studied using a Monte Carlo model. The model is used to
      determine if receptor inactivation affects G-protein activation and thus the
      following signaling events for cases of equal equilibrium receptor occupation by
      agonist. The model predicts that receptor inactivation by antagonist binding
      results in lower G-protein activation not only by reducing the number of
      receptors able to bind agonist but also by restricting the movement of agonist
      among free receptors. The latter process is important to increasing the access of
      bound receptors to G-proteins.

PMID- 7631984
TI  - Physical measurements of bilayer-skeletal separation forces.
AB  - Bilayer membranes are intrinsically fluid in character and require stabilization
      by association with an underlying cytoskeleton. Instability either in the
      membrane-associated cytoskeleton or in the association between the bilayer and
      the skeleton can lead to loss of membrane bilayer and premature cell death. In
      this report measurements of the physical strength of the association between
      membrane bilayer and the membrane-associated skeleton in red blood cells are
      reported. These measurements involve the mechanical formation of long, thin
      cylinders of membrane bilayer (tethers) from the red cell surface.
      Ultrastructural evidence is presented indicating that these tethers do not
      contain membrane skeleton and, furthermore, that they are deficient in at least
      some integral membrane proteins. By measuring the forces on the cell as the
      tether is formed and the dimensions of the tether, the energy associated with its
      formation can be calculated. The minimum force to form a tether was found to be
      approximately 50 pN corresponding to an energy of dissociation of 0.2-0.3 mJ/m2.
      Such measurements enable critical evaluation of potential physical mechanisms for
      the stabilization of the membrane bilayer by the underlying cytoskeleton. It is
      postulated that an important contribution to the energy of association between
      bilayer and skeleton comes from the increase in chemical potential due to the
      lateral segregation of lipids and integral proteins.

PMID- 7631986
TI  - [Ann. Dermatol. Syph., 1868;1:1].

PMID- 7631985
TI  - Kinetics of cell detachment: effect of ligand density.
AB  - Cell adhesion to substratum is often mediated by binding between cell surface
      receptors and substrate ligands. Substrates can be derivatized with different
      types and densities of ligands, but how substrate chemistry determines cellular
      function, such as adhesion strength, has not been demonstrated quantitatively. We
      employ a numerical methodology developed by Dembo and colleagues (9), who
      investigated membrane peeling under conditions of excess ligand density, to
      investigate the kinetics and strength of cell peeling from ligand coated surfaces
      for arbitrary ligand density. We show there are two asymptotic limits to peeling
      strength, as quantified by the critical tension: a high ligand density limit,
      where the critical tension is independent of ligand density and depends
      logarithmically on the receptor density; and a low ligand density limit, in which
      the critical tension depends logarithmically on the ligand density but is
      independent of receptor density. In between these limits, we numerically
      determine the critical tension. The critical tension is always a weak function of
      the dissociation constant between ligand and receptor. Furthermore, we show how
      the rate of peeling, for tensions above the critical tension, depends on ligand
      density and the mechanical properties of the receptor-ligand bonds.
      Interestingly, we illustrate when small increases in ligand density should alter
      cellular behavior, inducing a change to spreading onto a substrate from peeling
      up from a substrate. In total the predictions of this paper provide criteria for
      the design of ligand-coated substrate that provide for the proper adhesion
      strength and dynamics of detachment of cells from surfaces.

PMID- 7631987
TI  - [Cutaneous reactions to gold salts].
AB  - OBJECTIVE: Evaluate the clinical features of skin reactions to gold salts.
      INTRODUCTION: Gold dermatitis is described in the literature as a group of
      reactions non-specifically associated with these drugs. PATIENTS AND METHODS: Ten
      patients (7 males, 3 females, mean age 59.6 years [corrected] with a skin
      reaction were studied over a 6 year period. All were treated with Allochrysine
      for rheumatoid arthritis (n = 8), rhizomelic pseudopolyarthritis (n = 1) or
      arthropathic psoriasis (n = 1). RESULTS: The delay to the first signs was from 2
      weeks to 8 months. Three lichenoid eruptions (including two with buccal lesions
      and two which followed an autonomous course), 2 pityriasis rosea (one with
      eosinophilia and one with liver disease), 2 eczematoid dermatoses and one
      urticaria were observed. Pathology examinations (8/10) were in agreement with
      clinical diagnosis. Imputability was 14 (1 case), 13 (8 cases) and 12 (1 case).
      DISCUSSION: The clinical features observed were variable and in agreement with a
      particular clinical situation. They were not specific to gold salts and cannot be
      qualified as "gold dermatitis". Two autonomous and severe lichenoid eruptions
      were observed. Generalized lesions were associated with biological signs. This
      situation must be considered as a marker of severity.

PMID- 7631988
TI  - [Lichenoid eruption induced by gold salts. An autonomous eruption].
AB  - INTRODUCTION: We report a severe lichenoid drug eruption due to gold salts which
      relapsed 8 months after the cessation of chrysotherapy. CASE REPORT: A 56 year
      old man, 3 months after the beginning of a gold sodium propanol sulfonate
      therapy, developed a polymorphous eruption with violin papules on the trunk,
      eczematous lesions on the limbs and erosive stomatitis. Gold salts were
      definitively withdrawn. We saw the patient four months after gold therapy
      cessation: the eruption remained and diagnosis of severe drug cutaneo-mucous
      lichenoid eruption was done. We saw thereafter the patient again, 8 months after
      gold therapy cessation: the eruption had relapsed, more intense. DISCUSSION: We
      suggest that lichenoid eruption, first caused by gold salts, has become
      autonomous.

PMID- 7631989
TI  - [Congenital atrichia with cysts].
AB  - INTRODUCTION: Congenital atrichia with papular lesions is a rare congenital
      ectodermic dysplasia. CASE REPORT: A male child had atrichia of the scalp and
      eyebrows from birth. The atrichia was associated with epidermic cystic lesions of
      the scalp. Biopsy showed cystic piler follicles within the derma surrounded with
      an inflammatory infiltration of multinucleated giant cells. DISCUSSION: In most
      reported cases, scalp hair is present at birth and then falls within the first
      three months of life. Follicular cysts appear later. This syndrome generally
      occurs sporadically and the mode of inheritance is unknown.

PMID- 7631990
TI  - [Multicenter histiocytosis].
AB  - INTRODUCTION: Multicentric histiocytosis is a rare systemic disease with active
      episodes and prolonged periods of remission. Immunosuppressor treatment
      (alkylating agents) can be effective. CASE REPORT: A new case of multicentric
      histiocytosis was observed in a 38-year-old man who was successfully treated with
      cyclophosphamide at the dose of 100 mg/d. Treatment was withdrawn after several
      weeks due to drug-induced hepatitis and replaced with chlorambucil at the dose of
      0.1 mg/kg/day for 6 months. No relapse has occurred after a follow-up of 14
      months. DISCUSSION: This case is particularly interesting because of the
      exceptional nature of spontaneous haemarthrosis which was the inaugural sign of
      joint manifestations with mediastinal lymph nodes and initially isolated pruritus
      occurring before the typical skin manifestations. Different management protocols
      have been discussed with emphasis on the presence of acute cyclophosphamide
      induced hepatitis. This immunosuppressor is not usually hepatotoxic. CONCLUSION:
      This case demonstrates the systemic nature of the disease and emphasizes the
      beneficial effect of alkylating agents.

PMID- 7631991
TI  - [Chronic herpes resistant to acyclovir in a patient with AIDS].
AB  - INTRODUCTION: The prevalence of mucocutaneous herpetic infection is especially
      high in patients with the acquired immunodeficiency syndrome (AIDS). In these
      patients, 8 p. 100 of the chronic or recurrent herpetic lesions are due to a
      mutant strain. CASE REPORT: A case of very large (900 cm2) genital chronic
      herpetic infection is reported in a patient with AIDS (stade C3-CDC/WHO 1993). It
      was characterised by an acyclovir resistant strain which emerged after several
      anterior treatment with acyclovir. A treatment with foscarnet was administered
      and clinical improvement was observed as early as the fourth day, with complete
      reepithelialization 50 days later. DISCUSSION: We discussed essentially the
      pathogenicity of the herpetic infections due to mutant strains in
      immunocompromised patients and on the therapeutic modalities. At the present
      time, foscarnet is the treatment of choice for acyclovir-resistant mucocutaneous
      herpes simplex.

PMID- 7631992
TI  - [Cutaneous rhabdomyosarcoma].
AB  - OBJECTIVE: The occurrence of a rare alveolar rhabdomyosarcoma in a 16-year old
      girl seems worth of a case report. OBSERVATION: A large multinodular tumor
      developed on the buttocks and the external genitalia; systemic symptoms and
      metastases of lymph nodes and skin occurred very soon and the disease had a
      lethal outcome within 16 months. A temporary regression was observed after
      polychemotherapy with daunorubicine, vincritine and 5-fluoro-uracile. COMMENTS:
      In children the rhabdomyosarcoma is the most frequent sarcoma of soft tissues;
      the poor prognosis of the alveolar type is assessed by the case of this 16-year
      old girl; this tumor may progress as a systemic disease and present as a leukemia
      with rapid impairment of general health, enlargement of lymph nodes, cutaneous
      nodules and anemia.

PMID- 7631993
TI  - [Porphyria cutanea tarda induced by HMG CoA reductase inhibitors: simvastatin,
      pravastatin].
AB  - INTRODUCTION: Based on experimental data, HMG CoA reductase inhibitors are
      theoretically contraindicated in patients with porphyria. These new cholesterol
      lowering drugs are increasingly being prescribed. We report the first case of
      drug-related porphyria cutanea tarda due to HMG CoA reductase inhibitors. CASE
      REPORT: Porphyria cutanea tarda was diagnosed in a patient with chronic
      alcoholism 18 months after beginning a treatment with simvastatin followed by
      pravastatin. These drugs were given under different trade names and reintroduced
      successively leading to acute episodes. Total withdrawal of HMG CoA reductase
      inhibitors was followed by clinical normalization. COMMENTS: This case confirmed
      the theoretical contraindication for the use of HMG CoA reductase inhibitors in
      patients with porphyria. The risk of revealing porphyria with this type of
      cholesterol lowering drugs is emphasized. Since these drugs are used very
      frequently, similar cases may well be reported soon.

PMID- 7631994
TI  - [Necrotizing vasculitis induced by cytomegalovirus in a woman with acquired
      immunodeficiency syndrome].
AB  - INTRODUCTION: Skin lesions induced by cytomegalovirus are rare and usually non
      characteristic. CASE REPORT: A 32-year-old women with AIDS developed about twenty
      unpainful ulceronecrotic lesions on the extension aspect of the members and the
      trunk. Histology examination and in situ hybridization favoured cytomegalovirus
      infection of the skin. DISCUSSION: Despite the exceptional nature of this case,
      this particular clinical presentation should be recognized as it could be useful
      for early diagnosis of cytomegalovirus infection in immunodepressed subjects.

PMID- 7631995
TI  - [Cutaneous manifestations of infections caused by human Herpesvirus 6].

PMID- 7631996
TI  - [A case for diagnosis: tricholemmoma developed on a sebaceous hamartoma].

PMID- 7631997
TI  - [A case for diagnosis: bone involvement disclosing basal cell hamartoma].

PMID- 7631998
TI  - [Epidermal cytokines and cutaneous inflammation].

PMID- 7631999
TI  - [Photosensitivity, photocarcinogenesis and phototherapy in acquired
      immunodeficiency syndrome].

PMID- 7632000
TI  - [Contact allergic airborne dermatitis].

PMID- 7632001
TI  - [Cutaneous corynebacterioses].

PMID- 7632002
TI  - [Monthly question: How must surgeons wash their hands?].

PMID- 7632003
TI  - [Is it dangerous to use sunscreen agents?].

PMID- 7632004
TI  - [Progressive macular confluent hypomelanosis in mixed ethnic melanodermic
      subjects: an epidemiologic study of 511 patients].
AB  - INTRODUCTION: The pathogenesis of the recently described (1985) entity macular
      confluent progressive hypomelanosis in black subjects of mixed ethnic origin,
      also called creole dyschromia is unknown. Patients are generally black adults of
      mixed ethnic origin and present with hypopigmented maculae located asymmetrically
      in unexposed areas. The mechanism appears to be a phenotypic modification of
      produced melanosomes. The cases published to date do not provide clear
      epidemiological data. MATERIALS AND METHODS: We took histories and examined 511
      patients in the French West Indies (Martinique) during systematic screening for
      leprosy. Observations included presence or absence of creole dyschromia, the
      intensity of the depigmentation. History reports included chronology of the
      lesions and factors affecting disease course. RESULTS: One-hundred twenty-one
      cases of dyschromia were identified, often with few clinical signs. Creole
      dyschromia was found in one-third of the examined subjects between the age of 17
      and 48 years and appeared to be more exception outside this age range. More men
      than women were found to have the disease and the duration of the clinical course
      was about 25 years. Clearer skin appeared to be more sensitive and only responded
      to intermittent exposure to sun. DISCUSSION: Due to the fact that the examination
      was mandatory, it was possible to identify a large number of cases unknown to
      dermatologists and sometimes to the subject himself. The clinical description
      corresponded to those given in the literature, but the higher frequency in males,
      the duration of the clinical course and the sensitivity of clearer skin appear to
      have been unreported to date.

PMID- 7632005
TI  - [Combination of dacarbazine, vindesine and interferon alpha in the treatment of
      metastatic melanoma].
AB  - INTRODUCTION: The aim of this work was to study the effectiveness and safety of a
      combined therapy with dacarbazine, vindesine and alpha-interferon in the
      treatment of metastatic melanoma. PATIENTS AND METHODS: Thirty-one patients (20
      with visceral metastases and 11 with regional skin and lymph nodes metastases)
      were treated with dacarbazine (400 mg/m2 i.v. every 28 days), vindesine (3 mg/m2
      i.v. every 14 days) and recombinant interferon alpha 2b (Introna) 10 x 10(6) UI
      subcutaneously three times weekly. RESULTS: All patients at least received 3
      cures of chemotherapy. The response rate was 22.6 p. 100 with an average of 3.6
      months and an average deviation of 7.2 months. The responders were predominantly
      patients with lymph nodes (50 p. 100) and lung metastases (25 p. 100). Response
      was better in patients with no more than two metastatic sites. The treatment was
      well tolerated. DISCUSSION: This combined chemotherapy with 3 drugs not
      significantly increase either the response rate or its duration. However, the
      quality of life was good.

PMID- 7632006
TI  - [Iga linear bullous dermatosis in children. A series of 12 Tunisian patients].
AB  - BACKGROUND: Linear IgA bullous dermatosis (LABD) of childhood is one of the
      chronic, non-hereditary blistering diseases of childhood in which clinical,
      histologic and therapeutic findings are similar to those associated with bullous
      pemphigoid (BP) and dermatitis herpetiformis (DH). LABD, however, can be
      distinguished from BP of DH by direct immunofluorescence (IF) demonstration of
      linear IgA deposits along the basement membrane zone (BMZ). RESULTS: During the
      period 1984-1993, 12 children with LABD were studied. Their ages ranged from 2
      years to 15 years with a mean of 8.5 years. There were 7 males and 5 females. All
      children had a generalized eruption consisting of large tense blisters arising on
      normal skin. The blisters were more profuse on the lower trunk, pelvic region and
      limbs. Face and scalp were also affected. Occasionally, annular blister formation
      producing a "rosette" or "cluster of jewels" was found. Pruritus was frequent.
      Histological features of BP and DH were seen. Direct IF showed linear deposits of
      IgA at the BMZ in all cases. IgM, IgG, and complement were also seen in 8 cases.
      Four patients showed IgA BMZ antibodies by indirect IF. There were no symptoms of
      malabsorption and 3 patients had a mild bowel lesions. HLA studies showed the
      B8DR3 antigen in 7 of the 10 patients studied. Nine patients were treated with
      dapsone associated in 3 patients with prednisone. Three patients were controlled
      on oxacillin. CONCLUSION: LABD of childhood is a definite clinical entity. It is
      the most frequent chronic, non hereditary bullous disease of childhood in
      Tunisia. It is characterized by a self limiting blistering eruption which
      resembles BP or DH histologically and has a characteristic linear deposits of IgA
      at the BMZ of the skin. The treatment consisted on dapsone therapy, but 3
      patients in our study were well controlled on oxacillin.

PMID- 7632007
TI  - [Pachydermoperiostosis. An ultrastructural study].
AB  - BACKGROUND: Pachydermoperiostosis (PDP) is a rare genetically determined disease
      belonging to the group of hypertrophic osteoarthropathies. Its aetiopathogenesis
      remains unclear. Most hypotheses favour an exogenous stimulation of fibroblasts.
      METHODS: A clinically typical patient with PDP was studied by electron microscopy
      with particular reference to the dermis and its cellular constituents.
      Fibroblasts from involved skin were cultured and studied in comparison with
      control cells. RESULTS: Remarkable modifications of the structure of the dermis
      were observed, encompassing irregular caliber of collagen fibres, extracellular
      deposits of microfibrils and of amorphous granular substance corresponding to the
      Alcian blue positive deposits seen by conventional histochemistry. The in vitro
      growth of fibroblasts was normal. CONCLUSION: Authors reviewed aetiopathogenic
      hypotheses. Our data suggest a genetically determined alteration of extracellular
      matrix production by fibroblasts as a possible explanation for the development of
      PDP.

PMID- 7632008
TI  - [Multifocal epithelioid hemangioendothelioma with partial remission after
      interferon alfa-2a treatment].
AB  - INTRODUCTION: Epithelioid hemangioendothelioma (EHE) is a rare vascular tumour of
      the soft tissue having an intermediate malignancy. Cutaneous presentations have
      exceptionally been reported. OBSERVATION: A young woman, initially affected by an
      EHE with cutaneous and bone involvement, then with pulmonary and hepatic
      localizations, was in partial remission after one year of treatment with alpha 2a
      interferon. DISCUSSION: In a critical review of the literature, we describe the
      main features of this tumour and the difficulties to classify this entity in the
      vascular tumors' spectrum. Histologically, epithelioid hemangioendothelioma has a
      very characteristic appearance and is clearly different from other vascular
      tumors as angiolymphoid hyperplasia with eosinophilia and Kimura's disease. The
      assumption of a multicentric or a metastatic origin when multiple tumor deposits
      are found, is still not elucidated. Different therapeutic approaches are
      proposed: surgery, interferon, interleukin-2, retinoids. Randomized studies would
      be necessary to confirm our results with alpha 2a interferon but are probably
      difficult to realize because of the lack of cases.

PMID- 7632009
TI  - [A case for diagnosis: Kawasaki disease in the adult].

PMID- 7632010
TI  - [A case for diagnosis: anthrax of the eyelids].

PMID- 7632011
TI  - [Merkel cell].

PMID- 7632012
TI  - [Ossification and cutaneous osteoma].

PMID- 7632013
TI  - [Monthly question: swimming pools and infectious skin diseases?].

PMID- 7632014
TI  - [Exploration of the thoracic aorta. Excluding the aortic valve].
AB  - MRI has become the reference technique for the diagnosis and assessment of
      thoracic aortic aneurysms and subacute or chronic aortic dissections, and in the
      postoperative surveillance of the thoracic aorta. Several MRI techniques can now
      be used to investigate the thoracic aorta. The technique most widely used at the
      present time is Spin Echo imaging, which allows a multi-plane morphological
      approach to the thoracic aorta. It is often completed by a dynamic gradient echo
      sequence (cine-MRI) and, more recently, by ultra-rapid sequences (Turbo-Flash)
      following the injection of contrast agent. Phase-coding has also been proposed
      for the various intraluminal velocities. In the emergency situation, the
      examination of choice is less clearly defined due to the development of new
      techniques (transoesophageal ultrasonography, spiral computed tomography, MRI).
      The diagnostic strategy depends on the patient's clinical state, the respective
      advantages and limitations of each technique and the human and material resources
      available.

PMID- 7632015
TI  - [Evaluation of congenital cardiopathies].
AB  - In this article, the different MRI methods used for the evaluation of congenital
      heart diseases are described and the role of this technique in complement to the
      other classical methods such as echocardiography and cardiac catheterization.
      Description of the MRI techniques is first realized, then the contribution of MRI
      in different types of congenital heart disease is specified with emphasizing of
      the specificity of the method in each case, particularly in complex diseases.

PMID- 7632016
TI  - [MRI in cardiology: clinical applications and perspectives].
AB  - MRI is an effective tool in the evaluation of cardiovascular diseases. With
      continued improvements in MR angiography, velocity mapping, myocardial tagging,
      imaging speed and display, it is anticipated that MRI will play an ever
      increasing role in the morphological evaluation of many cardiovascular anomalies.
      The need for quantification in cardiology has led to the development of a variety
      of techniques to assess cardiac size and function. In attempting to answer these
      clinical questions, MRI provides major advantages several: extraordinary
      flexibility, powerful contrast mechanisms, sensitivity to flow and motion, and
      freedom from ionizing radiation, contrast agent and acoustic windows. Because of
      accurate initial results in quantifying cardiac chamber size, global and
      segmental function, it is likely that MRI methods will play an increasing role in
      the evaluation of cardiac structure and function. Recently, MRI has emerged as an
      important tool in the evaluation of great vessel disease, particularly in the
      evaluation of both congenital and acquired abnormalities of the aorta. Early
      evidence suggests that magnetic resonance may help in distinguishing constrictive
      pericarditis from restrictive cardiomyopathy (e.g., amyloid heart disease).
      Cardiac-MRI lends itself to assessment of intracardiac masses. Spin-echo imaging
      alone is often sufficient for diagnosis. Cine-MRI has important additive value,
      however, when a mass lesion shows dynamic motion, or when abnormal flow patterns
      in conjunction with a mass lesion require evaluation.

PMID- 7632017
TI  - [Exploration of renal arteries by angio-MRI].
AB  - Major clinical challenges are involved in applications of MR-angiography for the
      study of renal arteries, mostly for the diagnosis of renovascular hypertension.
      This technique now competes with color Doppler flow sonography and spiral CT. MR
      angiography of the renal arteries can be performed with 2D or 3D, flight-time or
      phase contrast sequences. Main and co-dominant arteries are usual by visualized
      on all sequences, but small accessory arteries are often missed. The diagnosis of
      stenosis is based on the presence of an area of signal extinction. The degree of
      extinction depends on the degree of turbulence, the type of technique, the length
      of TE and spatial resolution parameters, which is why scoring of stenoses is
      difficult and frequently overestimated. The diagnostic performance for stenosis
      is between 50 and 100% for sensitivity and between 80 and 97% for specificity.
      Detection of distal stenoses is poor because of respiratory artifacts. Multiphase
      acquisitions make it possible to measure the renal blood flow on each renal
      artery, adding hemodynamic criteria to this diagnosis.

PMID- 7632018
TI  - [Principles of magnetic resonance angiography].
AB  - Magnetic resonance angiography is a modality of functional imaging which can only
      be interpreted on the basis of a good understanding of vascular physiology and
      the physical principles of image acquisition. Magnetic resonance angiography is
      based on flow-related "artefacts". The oldest method is based on renewal of the
      image by proton flow: the flight time effect. Dephasing of the protons travelling
      in magnetic field gradients results in phase-contrast angiography. These two
      methods of angiography each have respective advantages and disadvantages: they
      are not mutually exclusive, but complementary.

PMID- 7632019
TI  - [Exploration of vessels of the lower limbs by magnetic resonance angiography
      (MRA)].
AB  - Interesting results are beginning to be published in the literature concerning
      the capacities of MRA in arterial disease and thrombophlebitis of the lower
      limbs. The acquisition techniques reported in the limited number of papers
      published in the literature are unfortunately too disparate to be applied to
      routine diagnostic activity. Most teams agree on the fact that the axial plane is
      the most suitable to visualize arteries of the lower limbs in patients with
      arterial disease, using 2D acquisition with or without intravenous injection of
      paramagnetic contrast agent. Based on the experience acquired with the use of
      multiple sequences obtained in 24 subjects (4 healthy volunteers, 12 patients
      with arterial disease and 8 cases of suspected thrombophlebitis) and a review of
      the literature, the potential applications and limits of MRA have been defined as
      a function of the capacities of current machines. MRA is able to detect venous
      thrombi and can also provide a complete assessment of arterial stenosis and
      occlusions in arterial disease of the lower limbs. The only drawback of the
      technique in arterial disease is the number of sections required, as only the
      axial plane can be used for acquisition. Consequently, MRA is tending to be
      developed in specific indications such as topography of arteries suitable for
      bypass procedures, rather than as a substitute to classical angiographic arterial
      mapping, although it appears to be superior to arteriography of the lower limbs
      in some cases in terms of the information it provides on the distal blood supply
      in the case of proximal occlusion. The problem which remain to be resolved are
      the reduction of the number of sections and the choice of the optimal field of
      view. Assuming that the technique is accepted by vascular surgeons, examinations
      composed of non-contiguous sections would appear to constitute a sufficient
      diagnostic solution. In thrombophlebitis, the problem is not so much the blood
      flow as extent of the thrombus. The diagnosis is easy in the case of fresh
      thrombus (which has a high-intensity signal, like subacute haematoma), but
      appears difficult or even impossible in the case of phlebitic sequelae.

PMID- 7632020
TI  - [Role of NMR in the diagnosis of atherosclerosis].
AB  - Diagnosis and prognosis of atherosclerosis can no longer be evaluated with
      morphological parameters only. A description of atherosclerotic plaque
      composition is necessary to study the mechanisms of plaque rupture, which depends
      on collagenous cap and lipid core thicknesses. NMR, as a biochemical imaging
      technique, allows visualization of these components using T1 contrast (mobile
      lipids), T2 contrast (cap vs. core), spin density (calcifications), diffusion
      imaging, 1H and 13C spectroscopy. Today, these imaging sequences allow to study
      in vitro the effects of interventional techniques such as angioplasty or
      atherectomy. Clinical investigations begin, which will attempt to develop in vivo
      microscopy and test the ability of NMR to predict plaque rupture.

PMID- 7632021
TI  - [Morphological and functional study of pulmonary arteries by MRI].
AB  - This article presents an exhaustive review of MRI in the assessment of the
      pulmonary arteries (sequences, normal results, clinical signs of the main
      diseases). Its current preferential indications are: the study of the main
      pulmonary artery trunks (primary tumours, proximal embolism, caliber
      abnormalities, anatomical relations with central tumours), the assessment and
      post-treatment follow-up of pulmonary arterial malformations. Angio-MRI is
      currently being developed and, in the near future, should allow the reliable
      diagnosis of pulmonary embolism and will therefore be indicated alongside spiral
      computed tomography. MRI also allows functional assessment of the right
      circulation (measurements of circulatory velocity and flow rates). It should
      rapidly become an examination of choice in the haemodynamic follow-up of patient
      with pulmonary hypertension and transplant recipients and as an evaluation tool
      for new drugs.

PMID- 7632022
TI  - [Congenital mitral insufficiency. Diagnosis, prognosis and treatment].
AB  - Between September 1973 and November 1993, 30 children with CMI underwent open
      heart surgery. The mean age at operation was 6.63 years with a range of 8 months
      to 14 years. Twenty patients underwent reconstructive mitral valvuloplasty; 3
      immediate failures and 1 case of stenosis of Carpentier's ring, occurring 7 years
      after the operation, were observed in this group. Among the 10 patients treated
      by mitral valve replacement, there were 4 deaths, including 3 from specific
      complications of the prosthesis. Conservative mitral surgery provides better
      results with far fewer complications that mechanical prostheses and must
      therefore always be attempted as the first-line procedure.

PMID- 7632023
TI  - [Vector-echocardiographic correlations in left ventricular hypertrophy of
      arterial hypertension].
AB  - In almost 200 case of left ventricular hypertrophy (LVH) secondary to
      hypertension (HT), including 75 cases with conduction disorders, 100 cases of
      normal adults and 20 cases of normal children, segmental (initial horizontal
      vector, maximal anterior and posterior vector of the QRS) and spatial vectorial
      parameters were correlated to segmental echocardiographic parameters (septum,
      anterior and posterior wall of the left ventricle) and mass parameters (left
      ventricular mass index). The only significant quantitative variables in
      hypertensive LVH are: on electrocardiography: the AQRS and Sokolow's index: on
      vectocardiography: the spatial vector: its magnitude, azimuth and elevation, the
      maximal posterior vector: its amplitude, the maximal anterior vector: its
      amplitude, the maximal width of the QRS azimuth of the efferent limb of the QRS,
      the ventricular gradient in the horizontal, frontal and sagittal planes; on
      echocardiography: the left ventricular mass index, the diastolic thickness of the
      septum and the VMNES, the diastolic thickness of the posterior wall of the left
      ventricle and its percentage thickening. The only significant correlations were
      observed between: the maximal posterior vector of QRS and the diastolic thickness
      of the posterior wall of the left ventricle: 0.01 < alpha < 0.02; the spatial
      vector and the left ventricular mass index: 0.01 < alpha < 0.001. The presence of
      a conduction disorder does not modify these last two qualitative variables but
      alters their correlation.

PMID- 7632024
TI  - [Cardiovascular manifestations caused by Mycoplasma pneumoniae. Apropos of a case
      of recurrent pericarditis complicated by tamponade].
AB  - The authors report a case of recurrent pericarditis complicated by tamponade, a
      complication rarely reported in the literature, due to Mycoplasma pneumoniae
      infection. The frequency and the characteristics of the pericarditis caused by
      this microorganism are reviewed and the diagnostic criteria and pathogenic
      mechanisms are discussed.

PMID- 7632025
TI  - [Refractory sinus tachycardia: late complication of radiotherapy].
AB  - The authors describe a case of sinus tachycardia, an unusual cardiac complication
      of mediastinal radiotherapy; occurring in two patients by the first days of
      treatment and persisting for several years. No other cause for this tachycardia
      could be detected in either case. Electrophysiological investigation of one of
      the two patients was normal. Despite the risk of a high-degree conduction
      disorder, "symptomatic" beta-blocker treatment was prescribed, but only induced a
      limited effect.

PMID- 7632026
TI  - [Association of coronary-pulmonary fistula and intercoronary fistula. Apropos of
      a case].
AB  - The authors present the case of a 30-year-old woman admitted to hospital for
      investigation of a systolodiastolic murmur. Assessment revealed a fistula between
      the trunk of the left coronary artery and the pulmonary artery, with an aneurysm
      on the left anterior descending artery (LAD), associated with an intercoronary
      anastomosis between the left conus artery and the LAD. Thallium myocardial
      scintigraphy demonstrated reversible decreased uptake in the anterolateroapical
      region. Simple coronaro-pulmonary fistulas are a rare disease. The positive
      diagnosis is suggested by echocardiography and confirmed by coronary angiography.
      The clinical course is generally favourable, except in the presence of
      complications such as aneurysm, heart failure or coronary insufficiency. This
      case raises the difficult problem of the operative indication in these young,
      usually asymptomatic patients.

PMID- 7632027
TI  - [Ablation of the bundle of His through a patent foramen ovale, by approach from
      the left side].
AB  - The authors report the case of a 60-year-old male patient in whom resection of
      the bundle of His via a right-sided approach to treat permanent very rapid atrial
      fibrillation was attempted, but failed. The bundle of His tissue was resected
      very easily on the left side due to the presence of a patent foramen ovale, which
      also avoided the risks of the left catheterism in this patient.

PMID- 7632028
TI  - [Hormone replacement therapy in postmenopausal women and cardiovascular risk].
AB  - Although the cardiovascular effects of hormone replacement therapy of menopause
      have been controversial for a long time, the benefit of this treatment currently
      appears to be well established, despite the methodological problems of most
      studies and the absence of definitive demonstration by a prospective randomized
      study. The mechanism of this favourable action appears to be multifactorial with,
      in particular, an improvement of the lipid profile. In the absence of any
      gynaecological contraindication, the combination of a natural oestrogen and a
      progestogen devoid of any androgenic effect therefore appears to be the
      preferable treatment in postmenopausal women, especially as its cardiological
      value is added to other important and clearly documented actions.

PMID- 7632029
TI  - [Value of the combination of trimetazidine (Vastarel 20 mg) with diltiazem
      (Tildiem 60 mg) in stable effort angina. A double-blind versus placebo
      multicenter study].
AB  - Trimetazidine is a cytoprotective anti-ischaemic agent whose antianginal efficacy
      has been demonstrated in monotherapy versus placebo and versus reference
      products, and in combination with beta-blockers and nifedipine. As coprescription
      with diltiazem has not been previously studied, the objective of this study was
      to evaluate the benefit of the addition of trimetazidine (60 mg/24 h) to
      diltiazem (180 mg/24 h) in the stable exertional angina insufficiently improved
      by calcium channel blocker alone. This multicentre double-blind placebo
      controlled study was conducted over a period of 6 months. The inclusion criteria
      were stable angina with electrically positive stress test, which remained
      positive despite a 15-day treatment with diltiazem (180 mg/24 h). It was
      conducted in 67 patients randomized into two groups: diltiazem-placebo (group I:
      35 patients) and diltiazem-trimetazidine (group II: 32 patients). The follow-up
      consisted of clinical assessment and a stress test on inclusion and at 6 months.
      The two groups were similar on inclusion for all ergometric parameters, excepted
      for the time to onset of the ischaemic threshold of 1 mm and the total duration
      of effort, which were significantly longer in the placebo group. Comparison of
      the stress tests performed at the sixth month and on inclusion between groups I
      and II showed that the ischaemic threshold of 1 mm was significantly delayed by 2
      minutes 41 seconds in the trimetazidine group (p < 0.001) versus 42 seconds in
      the placebo group (NS). Similarly, the work performed at this threshold was
      significantly increased by 1446 kpm in the trimetazidine group (p < 0.001) versus
      564 kpm in the placebo group (p = 0.012). The difference between the two groups
      was significant for these two parameters, p = 0.008 and p = 0.018, respectively.
      At maximum effort, the total duration and the total work also increased
      significantly in the trimetazidine group, by 50 seconds (p = 0.006) and 570 kpm
      (p = 0.004), respectively, versus 16 seconds and 221 kpm in the placebo group
      (NS). The [double product (SBP x HR)/load (in watts)] ratio at the ischaemic
      threshold of 1 mm reached at M0, decreased significantly in the trimetazidine
      group by 69.9 (p < 0.001) versus 20.3 in the placebo group (NS). The difference
      between the two groups was significant (p < 0.01).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7632030
TI  - The role of biochemical tests in the screening and monitoring of osteoporosis.

PMID- 7632031
TI  - Intra-individual factors affecting lipid, lipoprotein and apolipoprotein
      measurement: a review.

PMID- 7632032
TI  - Evaluation of human IgG subclass assays on Beckman array.
AB  - Automated immunonephelometric assays were developed to measure human IgG
      subclasses in serum, on the Beckman Array Protein System (APSR), with sheep
      antihuman IgG subclass antisera. The interassay imprecision was judged to be
      satisfactory in each case (CV: IgG1: 2.3%; IgG2: 2.9%; IgG3: 4.0% and IgG4 5.4%).
      The standard curves were found to be linear in the ranges 1.5-30.0 g/L for IgG1,
      1.5-15.0 g/L for IgG2, 0.1-1.0 g/L for IgG3 and 0.1-1.0 g/L for IgG4. The lower
      limit for quantification of the immunephelometric assays was 0.5 g/L for IgG1,
      0.04 g/L for IgG2, 0.06 g/L for IgG3 and 0.03 g/L for IgG4. We found no antigen
      excess to at least 60.0 g/L for IgG1 and IgG2, 3.5 g/L for IgG3 and 2.0 g/L for
      IgG4. Nephelometric results correlated with those of radial immunodiffusion (r =
      0.96 for IgG1, r = 0.93 for IgG2, r = 0.90 for IgG3 and r = 0.96 for IgG4). The
      reaction monitored by the Beckman Array Protein System is easy to perform, rapid
      and precise. The performance makes the immunonephelometric method suitable for
      the determination of IgG subclass concentrations in routine analysis.

PMID- 7632034
TI  - A specific radioimmunoassay for the determination of morphine-6-glucuronide in
      human plasma.
AB  - A specific antiserum for morphine-6-glucuronide (M6G) has been raised in a rabbit
      in response to immunization with a novel hapten:protein conjugate (N
      aminobutylnormorphine-6-glucuronide-thyroglobulin). Cross-reactivity with
      morphine and structurally related compounds was found to be negligible as
      expected from the nature of this immunogen. Using this antiserum, a simple, rapid
      and robust radioimmunoassay (RIA) has been developed for determination of M6G in
      samples of human plasma. The assay has a sensitivity of 0.05 ng/mL using 100
      microL sample volumes and affords complete recovery of M6G over the range 2-200
      ng/mL. The presence of morphine or morphine-3-glucuronide at concentrations up to
      100 times the levels of M6G did not result in any measurable interference. Close
      agreement was obtained between M6G results obtained using the RIA and a specific
      high-performance liquid chromatography assay. This RIA offers an attractive
      alternative to existing methods for the determination of M6G in human plasma and
      will facilitate further metabolic and pharmacokinetic studies of morphine and M6G
      in the clinical setting.

PMID- 7632033
TI  - Cerebrospinal fluid interleukin-6 and its diagnostic value in the investigation
      of meningitis.
AB  - We examined the measurement and the diagnostic value of cerebrospinal fluid
      interleukin-6 (CSF IL-6) in meningitis. The cytokine was measured by bioassay (B9
      hybridoma cell line) and by immunoassay (in-house radioimmunoassay). We compared
      the diagnostic value of CSF IL-6 determination with that of other biochemical
      markers of meningitis. Although there was significant correlation between
      bioactive and immunoactive IL-6 (r = 0.724, P < 0.001), results were frequently
      different with biological/immunological ratios ranging from 0.2 to 24.3 (mean
      4.6). Gel permeation chromatography suggested that the discrepancy in biological
      and immunological activities was not due to molecular heterogeneity, but may be
      explained by the presence of a synergistic factor. Interleukin-6 concentration
      was markedly elevated in CSF from most patients with bacterial meningitis
      compared to patients with viral meningitis and those without evidence of
      infection. However, low IL-6 levels by radioimmunoassay did not exclude bacterial
      meningitis (sensitivity 86%). CSF total protein and CSF glucose were
      significantly different between all three groups, but there was no significant
      difference in lactate concentration between virally infected and normal CSF, both
      of which had lower lactate concentrations than those in bacterial infection. CSF
      IL-6 measurement had greater sensitivity, specificity and predictive value than
      these other biochemical markers, and hence a rapid assay for IL-6 in CSF may
      contribute to the early diagnosis of bacterial infection.

PMID- 7632035
TI  - Plasma and urine sialic acid in non-insulin dependent diabetes mellitus.
AB  - Urinary excretions of albumin, glycosaminoglycans (GAGS), total sialic acid
      (TSA), and lipid associated sialic acid (LASA) were measured in 78 non-insulin
      dependent diabetic patients (NIDDM) and 28 healthy subjects. TSA excretion was
      significantly higher in normoalbuminuric and microalbuminuric diabetic subjects
      than the control subjects and TSA excretion was correlated with urinary albumin
      excretion rate (AER). In normoalbuminuric diabetics, the duration of diabetes
      correlated significantly with both sialicaciduria and albuminuria. Although serum
      TSA levels were significantly higher in both diabetic groups than the control
      subjects, there was no correlation between serum and urinary TSA levels.

PMID- 7632036
TI  - Thyroid stimulating hormone measurement using a third generation immunometric
      assay.
AB  - After an initial evaluation of the standard procedure for performance of a third
      generation TSH (thyroid stimulating hormone) assay (Amerlite TSH-30)
      modifications were made to standardize the timing of measurement of light
      emission following signal reagent addition. By adopting this optimized procedure,
      a significant improvement in assay sensitivity was achieved when compared to a
      second generation TSH assay (DAKO). Using the optimized assay the sensitivity was
      0.003 mU/L (20 replicates of zero) or 0.009 mU/L [22% CV (coefficient of
      variation) from the precision profile]. Recovery of added TSH and parallelism of
      the assay were good. A significant negative bias was detected for the Amerlite
      TSH-30 assay when compared to the DAKO assay (log y = 0.92 log x-0.33, n = 210).
      Excellent discrimination was achieved between euthyroid, hypothyroid and
      thyrotoxic subjects. A high percentage of thyrotoxic patients had undetectable
      TSH and the spread of values between thyrotoxic and euthyroid was greater with
      the third generation assay. In patients receiving thyroxine therapy a higher
      percentage had detectable TSH values. The optimized Amerlite TSH 30 assay offers
      improved assay performance when compared to a second generation assay.

PMID- 7632037
TI  - Determination of free triiodothyronine by six different methods in patients with
      non-thyroidal illness and in patients treated with amiodarone.
AB  - We performed a methodological comparison of free triiodothyronine (FT3) estimates
      in patients with liver cirrhosis and renal failure. Patients were classified in
      terms of severity of illness on the basis of their total triiodothyronine, total
      thyroxine and reverse triiodothyronine profiles. FT3 levels, measured in direct
      dialysis, microchromatography, labelled analogue and two-step immunoextraction
      assays were significantly (P < 0.01) lower than the control group in all patient
      categories. However, FT3 measured by a labelled antibody radioimmunoassay was
      significantly reduced only in the most severely ill sub-group of patients. In a
      further group of patients on long-term amiodarone therapy for cardiac disease all
      FT3 methods, with the exception of the labelled antibody radioimmunoassay and an
      analogue method, yielded significantly (P < 0.01) reduced levels. A significant
      negative association between FT3 and subject age was demonstrated for all methods
      except the labelled antibody radioimmunoassay, and a weak but significant
      negative correlation between log thyrotropin and FT3 was only seen with this
      assay. Three methods demonstrated a correlation (P < 0.02) with albumin levels in
      patients with the 'low T3 syndrome'. In this group, albumin had a predictive
      value (P < or = 0.02) for four out of six assays as determined by stepwise
      variable selection. Our findings suggest that users of FT3 assays should exercise
      caution in interpreting results in non-thyroidal illness and amiodarone treated
      patients, as there are method-related differences in the profiles obtained.

PMID- 7632038
TI  - Serendipity and glycated haemoglobin assay: discovery of a new haemoglobin
      variant.

PMID- 7632039
TI  - Immunoassay of collagen crosslinks in acidified urine.

PMID- 7632040
TI  - The Yellow Springs analyser gives lower results than other glucose oxidase
      methods of glucose measurement.

PMID- 7632041
TI  - A simple extraction procedure for the determination of carcinoembryonic antigen
      in gallbladder bile.

PMID- 7632042
TI  - Profound hypoglycaemia induced by propranolol in a patient with hepatic cirrhosis
      and severe hyperandrogenaemia.

PMID- 7632043
TI  - Stability of plasma glucose during storage.

PMID- 7632044
TI  - Interference by caffeine in theophylline measurement.

PMID- 7632045
TI  - Interference by caffeine in polarization fluoroimmunoassays for theophylline.

PMID- 7632046
TI  - Surgical patients with multiantibiotic-resistant bacteria.
AB  - Although antibiotics can cure most bacterial infections, there is an increasing
      number of bacteria that are resistant to antibiotics. Methicillin-resistant
      Staphylococcus aureus (MRSA) is becoming increasingly prevalent in US health care
      facilities. The majority of these infections are found in patients who have
      extensive burns or surgical wounds. As a result, perioperative nurses must be
      knowledgeable about MRSA and its implications for the OR. There are many theories
      on how to control the spread of MRSA but not one definitive set of control
      measures. Perioperative nurses, in cooperation with infection control
      practitioners, must develop policies that detail how patients with MRSA will be
      treated.

PMID- 7632047
TI  - Barrier protection and latex allergy associated with surgical gloves.
AB  - Latex continues to be the material of choice for surgical gloves because it is
      resealable and flexible, and it maintains the wearer's tactile sensitivity. The
      use of latex gloves for barrier protection may need to be reevaluated in light of
      the increasing number of individuals who are sensitive to latex. Hospital
      personnel can use low-allergen gloves or nonlatex gloves when caring for patients
      with known sensitivity to latex; however, only nonlatex gloves may be effectives
      at reducing or preventing anaphylactic reaction. Health care facilities must
      develop policies and procedures for dealing with latex-sensitive patients and
      health care workers.

PMID- 7632048
TI  - Reducing employee back injuries in the perioperative setting.
AB  - An ergonomic consultant conducted an evaluation of a 14-room surgical suite that
      had a high rate of employee back injuries. The consultant made five specific
      recommendations regarding moving patients, maneuvering carts and equipment, using
      gallbladder boards, walking on wet floors, and accessing power outlets. Most of
      the recommendations were implemented and well received. Eighteen months after the
      implementation of the consultant's recommendations, there was a 25% reduction in
      the number of back injuries among the OR staff members.

PMID- 7632049
TI  - Using a computerized scheduling system to predict procedure lengths.
AB  - To determine the effectiveness of our computerized OR scheduling system and
      database, we compared scheduled surgical procedure lengths to actual procedure
      lengths for a large, multispecialty sample (1,103 procedures in 14 surgical
      subspecialties). We were able to accurately predict procedure lengths, within 15
      minutes, 65% of the time. The estimated procedure lengths were more accurate in
      some surgical subspecialties than others, and four specific factors accounted for
      a large percentage (ie, 84%) of all delayed start times.

PMID- 7632050
TI  - How one chapter successfully created a nursing research committee.
AB  - Establishing a chapter nursing research committee can be a difficult task. Many
      perioperative nurses have not been exposed to research in their basic nursing
      programs or received graduate preparation in nursing research. This lack of
      exposure may result in disinterest in nursing research topics. This article
      explains how AORN of Pittsburgh established a successful nursing research
      committee. The committee's process of development and its achievements can be
      used as a guide for other local chapters that may be struggling with similar
      issues.

PMID- 7632051
TI  - Perioperative nurse practitioners.
AB  - Perioperative nursing roles are evolving in response to health care reform,
      technological developments, and changing opportunities for advanced practice
      nursing. One response to these changes is the development of the perioperative
      nurse practitioner role. The perioperative base for this new advanced practice
      role is described in this article. The advanced practice role is effective in
      other specialty settings and can be developed readily in a variety of surgical
      settings. This role requires a master's degree in nursing to provide the academic
      and practice preparation for clinical decision making and patient management in
      the perioperative setting. Future opportunities for perioperative advanced
      practice nursing are discussed.

PMID- 7632053
TI  - Recent nurse march on Washington, DC, designed to draw legislation.

PMID- 7632052
TI  - Barriers to pain management in elderly surgical patients.

PMID- 7632054
TI  - Fostering consumer demand for perioperative registered nurses is a top priority
      for AORN members.

PMID- 7632055
TI  - When health care champions become crispy, curly french fries, it's time for a
      reality check.

PMID- 7632056
TI  - Transsphenoidal adenomectomy.

PMID- 7632057
TI  - Award for Excellence in Perioperative Nursing recipient emphasizes nurses' value.

PMID- 7632058
TI  - Small bowel transplantation.
AB  - Small bowel transplantation (SBT) presents a formidable challenge to
      perioperative nurses. Patients who survive these procedures have difficult
      postoperative courses with lengthy intensive care stays. They also are at
      significant risk for graft rejection and long-term immunosuppression
      complications. The option for SBT is reserved for patients who otherwise face the
      prospect of life-long total parenteral nutrition (TPN). Advances in donor and
      recipient surgical techniques and improvements in immunosuppressive therapies
      have raised hopes that patients with intestinal failures who undergo SBT
      procedures will be allowed to resume full oral nutrition and independence from
      TPN.

PMID- 7632059
TI  - Granulocyte-macrophage colony-stimulating factor in the management of severe
      ecthyma gangrenosum related to myelodysplastic syndrome.

PMID- 7632060
TI  - Cutaneous ulceration and a new cardiac murmur in a young woman.

PMID- 7632061
TI  - Juvenile xanthogranuloma, neurofibromatosis, and juvenile chronic myelogenous
      leukemia. World statistical analysis.
AB  - BACKGROUND AND DESIGN: The concurrent finding of neurofibromatosis type 1 (NF),
      juvenile chronic myelogenous leukemia (JCML), and juvenile xanthogranuloma (JXG)
      has been repeatedly reported. Juvenile chronic myelogenous leukemia has been
      found more frequently in patients with NF and may present with various cutaneous
      manifestations, including JXG. To our knowledge, the relationship among these
      three entities has never been explored. The purpose of the present study is to
      explore this relationship by using a systematic review of the literature. We
      present five demonstrative cases of various associations among NF, JCML, and JXG.
      RESULTS: A family history of NF was found in 85% to 95% of children with NF and
      JCML (with or without JXG), as compared with that found in 47% of children with
      NF and JXG. The observed frequency of the triple association is 30-fold to 40
      fold higher than that expected. It is estimated that children with NF and JXG
      have a 20-fold to 32-fold higher risk for JCML than do patients with NF who do
      not have JXG. CONCLUSIONS: A concomitant finding of JCML and JXG in children with
      NF represents a true association, rather than a coincidence. A finding of JXG in
      an infant with NF should alert a physician to a possible development of JCML.

PMID- 7632062
TI  - bcl-2 expression in primary malignancies of the skin.
AB  - BACKGROUND AND DESIGN: Basal cell carcinoma (BCC), squamous cell carcinoma (SCC),
      and malignant melanoma (MM) are the three most common malignant neoplasms that
      arise in the skin. Deregulation of oncogene function not infrequently leads to an
      increased rate of cellular proliferation. However, the expansion of malignant
      cells can also occur if programmed cell death is inhibited. The oncogene bcl-2
      participates in the regulation of apoptosis (programmed cell death). In view of
      this, we determined the presence and possible role of bcl-2 in primary cutaneous
      malignancies. Routine paraffin sections of formalin-fixed BCCs, SCCs, MMs
      (primary and metastatic), actinic keratoses, and SCCs in situ were labeled with
      anti-bcl-2 monoclonal antibody using a biotin-avidin-immunoperoxidase procedure.
      RESULTS: Twenty-three BCCs were examined and all expressed cytoplasmic bcl-2. Two
      of 20 SCCs were positive. One of these had patchy, diffuse staining, and the
      other stained in only small foci. None of eight SCCs in situ and none of eight
      actinic keratoses expressed bcl-2. Sixteen of 18 MMs expressed bcl-2.
      CONCLUSIONS: The bcl-2 gene product has been found to inhibit apoptosis. Our
      preliminary results suggest that the expression of bcl-2 is present quite
      consistently in BCCs and MMs, but not in SCCs or precursor lesions. The
      expression (or lack thereof) of bcl-2 may reflect the difference in the
      regulation of cell turnover between these tumors, or histogenetic differences.

PMID- 7632063
TI  - bcl-2 expression in melanocytic nevi. Insights into the biology of dermal
      maturation.
AB  - BACKGROUND AND DESIGN: Recently, a new category of oncogenes has been discovered
      that regulate programmed cell death. The bcl-2 oncogene has been found to inhibit
      cellular death without affecting cellular proliferation. In the skin, bcl-2
      expression is limited to cells along the basal cell layer. However, we also
      noticed that resting melanocytes appeared to express bcl-2. We examined the
      expression of bcl-2 and its possible role in the biology of benign melanocytic
      proliferations. Routine paraffin sections of formalin-fixed tissue were labeled
      with anti-bcl-2 monoclonal antibody, and expression of bcl-2 was detected by a
      biotin-avidin-immunoperoxidase procedure. RESULTS: We examined 13 congenital, 11
      acquired, and six atypical or dysplastic nevi for expression of bcl-2. Expression
      of bcl-2 was observed in 11 of 13 congenital nevi. All 11 acquired nevi and 6
      nevi with architectural disarray and cytologic atypia expressed bcl-2. Both
      junctional and intradermal melanocytes expressed bcl-2 in a perinuclear and
      cytoplasmic pattern. Within neurotized areas, bcl-2 became significantly weaker
      and totally absent. CONCLUSIONS: In mature tissues, bcl-2 expression is quite
      limited. It appears to be restricted to pluripotential stem cells that serve as a
      reservoir for tissue that is constantly undergoing renewal, such as the
      hematopoietic cells and the intestinal mucosa. In the skin, bcl-2 expression has
      been previously reported to be limited to the epidermal basal cell layer and
      proliferation zones. Our results indicate that resting melanocytes and
      melanocytic nevi regularly express bcl-2.

PMID- 7632064
TI  - Treatment of toenail onychomycosis. A randomized, double-blind study with
      terbinafine and griseofulvin. LAGOS II Study Group.
AB  - BACKGROUND AND DESIGN: The fungicidal mode of action of terbinafine should make
      it feasible to reduce treatment duration in onychomycosis. For this reason, a
      randomized, double-blind study in 195 patients with severe dermatophyte
      infections of the toenails was performed comparing a 24-week treatment with
      terbinafine (250 mg/d) with a 48-week treatment with micronized griseofulvin
      (1000 mg/d). RESULTS: After 48 weeks, effective treatment was achieved in 67% of
      the patients treated with terbinafine and in 56% of those treated with
      griseofulvin (two-tailed P = .120). At a follow-up visit 24 weeks later, cure
      rates had decreased to 60% in the terbinafine group and to 39% in the
      griseofulvin group (two-tailed P = .006). At the same time, the mycological cure
      rate was 81% with terbinafine and 62% with griseofulvin (two-tailed P = .02).
      CONCLUSIONS: This study has demonstrated the longterm therapeutic superiority of
      terbinafine to high-dose griseofulvin in the treatment of toenail mycosis.
      Furthermore, with the new antifungal terbinafine, treatment is no longer
      necessary until all affected nail material has grown out.

PMID- 7632065
TI  - Antidepressant therapy. A possible cause of atypical cutaneous lymphoid
      hyperplasia.
AB  - BACKGROUND: Cutaneous pseudolymphomas were encountered in eight patients who were
      receiving the antidepressant (AD) medications fluoxetine hydrochloride and
      amitriptyline hydrochloride, which promote tumor growth and suppress certain
      lymphoid functions by inhibiting the binding of endogenous histamine to an
      intracellular histamine receptor designated HIC. OBSERVATIONS: Lesions appeared
      in all patients following the start of AD therapy and resolved or improved in all
      seven who discontinued AD therapy. Skin lesions were solitary in three patients
      and multiple in five. Four patients were being treated with other drugs that
      altered lymphocyte function, and three had underlying systemic diseases that were
      associated with immune dysregulation. There were four histological patterns:
      mycosis fungoides-like, lymphocytoma cutis, lymphomatoid vascular reaction, and
      follicular mucinosis. Common to the first group were histological features of
      delayed-type hypersensitivity reactions that enabled distinction from mycosis
      fungoides. More problematic was the distinction of lymphocytoma cutis lesions
      from low-grade lymphocytic neoplasms. The lymphocytoma cutis lesions were rich in
      B cells; the other cases were dominated by T lymphocytes. CONCLUSIONS: Cutaneous
      pseudolymphomas are associated with AD therapy, possibly reflecting perturbation
      of lymphoid function. Concomitant therapy with agents that have additive or
      synergistic immunomodulatory effects or an immune-dysregulating systemic disease
      may increase a patient's susceptibility to developing atypical cutaneous lymphoid
      hyperplasia while the patient is receiving AD therapy.

PMID- 7632066
TI  - Terbinafine for the treatment of pedal onychomycosis. A foot closer to the
      promised land of cured nails?
AB  - Onychomycosis of the nails includes fungal infection caused by primary nail
      pathogens that invade the healthy nail plate and secondary invasion in nails with
      preexisting disease. Onychomycosis may be due to secondary infection from tinea
      pedis and is the most common nail disease, accounting for roughly 30% of all
      cutaneous fungal infections. In a survey of 9332 British adults, 16 years of age
      and older, the prevalence of dermatophyte infection was 2.6% to 2.8%. In subjects
      55 years of age or older, the prevalence was 4.7%. In the United States, a
      similar prevalence has been reported. Onychomycosis can have a significant
      psychological effect on the subject. In a North American study, the relative
      composition of isolates from nails was dermatophytes (91%), yeasts (5%), and
      molds (4%). Candida is isolated predominantly from fingernails. Uncommonly, there
      are mixed infections. In other parts of the world, the frequency of these agents
      may vary.

PMID- 7632067
TI  - Skin, blood, nerve cells, and heritability. New lessons from neurofibromatosis
      type 1.

PMID- 7632068
TI  - Differential control of cell death in the skin.

PMID- 7632069
TI  - Amelanotic melanoma.

PMID- 7632070
TI  - Inflammatory papules on the back of a traveling businessman. Tumbu fly myiasis.

PMID- 7632071
TI  - Pruritus ani in an elderly man. Extramammary Paget's disease.

PMID- 7632072
TI  - Nail dystrophy. Systemic amyloidosis presenting with nail dystrophy.

PMID- 7632073
TI  - Leg ulcers and Klinefelter's syndrome.

PMID- 7632074
TI  - Segmental neurofibromatosis: is it uncommon or underdiagnosed?

PMID- 7632075
TI  - Severe erythema anulare centrifugum-like psoriatic drug eruption induced by
      terbinafine.

PMID- 7632076
TI  - Pilot study of topical calcitriol (1,25-dihydroxyvitamin D3) for treating
      psoriasis in children.

PMID- 7632077
TI  - Bacillary angiomatosis presenting as a malleolar ulcer.

PMID- 7632078
TI  - The significance of oral mucosal and salivary gland pathology after allogeneic
      bone marrow transplantation.

PMID- 7632079
TI  - Another sea pest.

PMID- 7632080
TI  - Omeprazole as a cause of oral candidiasis.

PMID- 7632081
TI  - High levels of soluble CD23 in blister fluid of patients with bullous pemphigoid.

PMID- 7632082
TI  - Quality of life--a measure too far?

PMID- 7632083
TI  - Retroviruses in rheumatic diseases.

PMID- 7632084
TI  - Skeletal evidence of osteoarthritis: a palaeopathological perspective.

PMID- 7632085
TI  - Beware the steroid responsive nature of a pyrexial illness.

PMID- 7632086
TI  - Work disability in early rheumatoid arthritis.
AB  - OBJECTIVE: To assess the impact of early rheumatoid arthritis (RA) on work
      status. METHODS: The employment status of 119 patients who had jobs before the
      onset of RA was examined. Patients with work disability were compared with those
      without, for several disease characteristics, therapeutic regimen, and
      educational level and age. RESULTS: Sixty two percent of the patients,
      particularly manual workers, reported some kind of work disability (7% worked
      less, 13% were on sick leave, and 42% had quit their jobs). Forty five patients
      (38%) stated that they were working without any restrictions; however, only 12 of
      this latter group (10% of the total group) had not encountered any changes at all
      within their jobs. The patients who reported work disability had a lower level of
      education and scored higher for several disease characteristics (erythrocyte
      sedimentation rate (ESR), joint tenderness, Health Assessment Questionnaire
      (HAQ), and Groningen Activity Restriction Scale) and were provided with more
      medication compared with patients without work disability, though only the
      educational level, disease duration, HAQ and ESR contributed significantly to
      work disability in logistic regression analysis. CONCLUSION: Even at an early
      stage, RA has a considerable impact on work status. This study indicates that
      work disability is dependent on disease characteristics and on the educational
      level of the patient.

PMID- 7632087
TI  - Ceiling effects of the Health Assessment Questionnaire and its modified version
      in some ambulatory rheumatoid arthritis patients.
AB  - OBJECTIVE: To examine if the reduced number of items in the modified version of
      the Health Assessment Questionnaire (MHAQ) concerning difficulty of performing
      activities of daily living may lead to a reduced ability to detect clinical
      changes compared with the original HAQ. METHODS: In 56 consecutive ambulatory
      patients with rheumatoid arthritis, we examined the mean change in clinical and
      laboratory parameters for those who recorded improved, unchanged, or worse MHAQ
      scores one year after a baseline assessment. RESULTS: At baseline, about 50% of
      the patients had an MHAQ score < 0.3 and clustered at the normal end of the
      scale. Because of a ceiling effect, the MHAQ failed to detect clinical
      improvement in 18% of the patients. Changes in clinical and laboratory parameters
      were associated with improved, unchanged, or worse scores with the HAQ but not
      the MHAQ. CONCLUSION: Although the format of the MHAQ has the advantage of
      eliciting a 'satisfaction' score, limitations in its sensitivity to detect
      clinical improvement in patients with relatively little difficulty in activities
      of daily living may not justify the use of this particular version of shorter
      questionnaire in certain clinical settings.

PMID- 7632088
TI  - Cellular immunity to cartilage link protein in patients with inflammatory
      arthritis and non-arthritic controls.
AB  - OBJECTIVES: To determine if increased T cell responses to articular cartilage
      link protein have any correlation with rheumatoid arthritis (RA), and if RA
      patients with increased responses to link protein also respond to a 17 amino acid
      peptide covering the 'arthritogenic' epitope in mycobacterial hsp65 which is
      homologous with link protein. METHODS: The reactivity of T cells from both
      peripheral blood and synovial fluid, to highly purified human cartilage link
      protein, hsp65, the 17 amino acid peptide, and bovine type II collagen was
      determined in patients with RA and nonarthritic controls, by measuring the rate
      of mononuclear cell proliferation in the presence and absence of antigen.
      RESULTS: Using peripheral blood mononuclear cells (PBMC), significant reactivity
      (stimulation index (SI) > 1.5) to link protein was found in 12 of 46 RA patients
      (26%), but in only four of 44 controls (9%). A greater proportion of RA patients
      (eight of 17:47%) were reactive to link protein when mononuclear cells from
      synovial fluid were tested. SI values, however, were generally low (0.5-3.1) and
      only one patient showed a PBMC response above a reference range of values
      calculated from the logarithmic values of the normal control population. No
      reactivity was observed against a 17 amino acid synthetic peptide including the
      arthritogenic epitope from the mycobacterial hsp65 to which T cell clones
      isolated from rats in the adjuvant arthritis model react. However, eight of nine
      RA patients and all of seven controls reacted to the intact hsp65. CONCLUSION: It
      remains unclear if T cell responses to link protein are involved in the
      pathogenesis of RA, but it is unlikely that T cells specific for the sequence
      homologous with the arthritogenic epitope in hsp65 are present in RA patients.

PMID- 7632089
TI  - Phospholipid binding specificities and idiotype expression of hybridoma derived
      monoclonal autoantibodies from splenic cells of patients with systemic lupus
      erythematosus.
AB  - OBJECTIVE: To analyse the phospholipid binding specificity, functional
      characteristics and idiotype expression of human hybridoma derived monoclonal
      autoantibodies (MAb) derived from the spleens of two patients with active
      systemic lupus erythematosus (SLE). METHODS: The IgM MAbs binding to
      phospholipids were generated from spleen cells of two patients (RSP and RT) with
      active SLE and their specificity of binding to neutral phospholipids
      (phosphatidyl ethanolamine, phosphatidyl choline, platelet activating factor,
      sphingomyelin) and negatively charged phospholipids (phosphatidyl glycerol,
      phosphatidyl serine, phosphatidic acid, phosphatidyl inositol and cardiolipin
      (CL)) analysed. Binding specificity of cross reactive antibodies (those binding
      to CL and DNA) was confirmed by fluid phase inhibition assays. Lupus
      anticoagulant activity and beta 2-glycoprotein-1 (beta 2 GP-1) requirement for
      the antigen binding of these MAbs were detected using the modified dilute
      Russell's viper venom test and modified anti-CL enzyme linked immunosorbent assay
      (ELISA), respectively. Expression of idiotypes (Id) Id RT-84 and Id H3 was
      analysed using rabbit polyclonal and murine monoclonal anti-idiotype reagents,
      respectively. RESULTS: Twelve clones from the patient RSP and eight clones from
      patient RT were reactive with phospholipids. Marked differences in phospholipid
      binding of these MAbs were noted, varying from truly polyreactive (RT-72 bound to
      most phospholipids tested) to monospecific (RT-84 bound only to CL). Furthermore,
      MAbs RT-84, RT-129, and RSP-57 had lupus anticoagulant activity and required beta
      2 GP-1 for CL binding. It was found that 75% of phospholipid binding antibodies
      from RT clones expressed RT-84 Id, but none from RSP clones did so, and that Id
      H3 was expressed only by the RT-83 antibody. CONCLUSION: These results show that
      human anti-phospholipid MAbs are heterogeneous with respect to phospholipid
      binding, functional characteristics, and Id expression.

PMID- 7632090
TI  - Appearance of calpain correlates with arthritis and cartilage destruction in
      collagen induced arthritic knee joints of mice.
AB  - OBJECTIVES: To determine the relevance of calpain in murine collagen induced
      arthritis (CIA) and to correlate the presence of m-calpain with the appearance of
      arthritis and cartilage destruction. METHODS: The immunohistochemical appearance
      and localisation of m-calpain at different stages of arthritis were analysed and
      compared with the histological changes occurring during type II CIA. The
      arthritic knee joint lavage was also examined for m-calpain by
      immunoelectrophoretic blotting. RESULTS: Immunohistochemical staining
      demonstrated a clear positive correlation between the appearance of m-calpain and
      both a histological grade of arthritis and an acute phase of cartilage
      destruction. Further development of the disease showed continual presence of m
      calpain but with reduced intensity. Intra-articular inflammatory cells (mainly
      polymorphonuclear leucocytes, synovial lining cells, and sublining fibroblasts)
      were found to be the most positively stained, but extracellular localisation of m
      calpain on the surface of cartilage and synovium, and in the articular cartilage
      matrix and chondrocyte lacunae, was also observed. In the knee joint lavage
      obtained at the most intensive stage of acute arthritis, m-calpain was detectable
      by immunoelectrophoretic blotting. CONCLUSIONS: The findings suggest that m
      calpain may act at an early phase of CIA as a matrix proteinase and take part in
      the destruction of articular cartilage or activate other destructive enzymes.

PMID- 7632092
TI  - Respiratory chain enzyme defects in patients with idiopathic inflammatory
      myopathy.
AB  - OBJECTIVE: To analyse muscle respiratory chain enzymes in idiopathic inflammatory
      myopathy. METHODS: Four consecutive female patients seen at our hospital with
      idiopathic inflammatory myopathy were studied. Muscle histochemical staining
      included NADH tetrazolium reductase and succinate dehydrogenase tests. Activity
      of rotenone sensitive NADH cytochrome c reductase (complex I and III) succinate
      dehydrogenase (complex II), succinate cytochrome c reductase (complex II and
      III), cytochrome c oxidase (complex IV), and citrate synthase (a mitochondrial
      matrix enzyme), was measured spectrophotometrically in muscle homogenates. Free
      carnitine, and short and long chain acylcarnitine esters were determined in
      muscle homogenates by a radiochemical procedure. RESULTS: Three patients had
      mitochondrial proliferation in nonregenerating muscle fibres; these patients had
      defects of respiratory chain enzyme complexes. Carnitine concentrations, measured
      in two of the four patients, revealed carnitine deficiency in one. CONCLUSION:
      Our results suggest that mitochondrial dysfunction may be present in patients
      with inflammatory myositis.

PMID- 7632091
TI  - Periarticular osteopenia in adjuvant induced arthritis: role of interleukin-1 in
      decreased osteogenic and increased resorptive potential of bone marrow cells.
AB  - OBJECTIVE: To clarify the local osteogenic and bone resorptive potential of
      periarticular bone in adjuvant induced arthritis (AIA). METHODS: Formation of
      fibroblast colony forming units (FCFU; osteogenic precursor cells) and osteoclast
      like cells in bone marrow culture was studied in AIA rats. Osteoclast-inducing
      activity in the AIA rat bone marrow was assayed by the addition of the marrow
      supernatant from rats with AIA to control cultures. Bone mineral density was
      determined by dual x ray absorptiometry. RESULTS: Marrow from AIA rats and that
      from animals receiving recombinant human interleukin-1 (IL-1) beta for seven days
      grew significantly fewer FCFU than control marrow. Formation of osteoclast-like
      cells was increased in bone marrow cultures from rats with AIA, especially when
      bone marrow cells were cultured in the presence of marrow supernatant. Formation
      of resorption lacunae on ivory slices was increased in the marrow cultures from
      rats with AIA, especially from the right (adjuvant inoculated) tibia. AIA rat
      marrow supernatant promoted osteoclast-like cell formation in control culture,
      and this was significantly suppressed by an anti-IL-1 antibody. Rats with AIA
      showed a significant decrease in the bone mineral density of the periarticular
      regions of the tibia and femur. CONCLUSION: An uncoupled state in bone resorption
      formation linkage, possibly mediated through an increase of IL-1 in the bone
      marrow, may contribute to the development of periarticular osteopenia in
      inflammatory arthritis.

PMID- 7632093
TI  - Cardiovascular functional disorder and stress among patients having neck-shoulder
      symptoms.
AB  - OBJECTIVES: To investigate if autonomic nervous system function, reflected in
      cardiovascular variables, among patients with neck-shoulder symptoms (tension
      neck group (T)) differed from that in a symptom free control group (C), and to
      establish its relation with pain and psychological stress. METHODS: Twelve women
      with tension neck and nine controls in secretarial jobs were studied. They
      underwent an orthostatic test, deep breathing test, Valsalva manoeuvre, isometric
      handgrip test, and muscular endurance test. Pain was measured using visual
      analogue scales, and psychological stress by the Modified Somatic Perception
      Questionnaire (MSPQ). Plasma endothelin-1 (ET-1) was measured using high pressure
      liquid chromatography and radioimmunoassay. RESULTS: Signs of psychological
      stress were significantly (p < 0.001) more common in group T than in group C.
      Mean resting heart rate in group T (77.8 (SE 2.9) beats/min; range 64-100) was
      significantly greater than that in group C (63.8 (3.1) beats/min; range 52-80) (p
      < 0.01). In the orthostatic test, the overall changes in R-R intervals during the
      first 40 heart beats after standing up and during seven minutes of testing
      differed significantly between the groups (p < 0.001, < 0.05, respectively). The
      increase in diastolic blood pressure in the three minute isometric handgrip test
      was significantly less in group T (19.4 (3.5) mm Hg; range -5 to 35) than in
      group C (30 (3.4) mm Hg; range 15-50) (p < 0.05). The MSPQ score in the study
      group (n = 21) correlated positively with resting heart rate (r = 0.462, p <
      0.05) and negatively with increase in diastolic blood pressure (r = -0.514, p <
      0.05). Plasma concentrations of ET-1 did not differ between the groups.
      CONCLUSION: Increased sympathetic activity was found among patients having neck
      shoulder symptoms. Local mechanisms may have influenced the cardiovascular
      changes observed during isometric testing in these patients.

PMID- 7632094
TI  - Association between human parvovirus B19 infection and arthritis.
AB  - OBJECTIVE: To gain information concerning the association between parvovirus B19
      infection and arthritis. METHODS: Blood or synovial fluid, or both, from a total
      of 77 adult patients with various arthropathies (rheumatoid arthritis 13;
      mechanical arthropathies 11; crystal induced arthritis 13; idiopathic
      mono/oligoarthritis 25; suspicion of viral arthritis 15) were tested for the
      presence of the viral genome and anti-B19 antibodies. B19 DNA in blood and
      synovial fluid was investigated by nested polymerase chain reaction, and anti-B19
      IgM and IgG antibodies were detected in blood by enzyme immunoassay. RESULTS: A
      recent parvovirus infection was documented by the presence of anti-B19 IgM
      antibodies in the blood of 13 patients. B19 DNA, together with anti-B19 IgM and
      IgG antibodies, were detected in the blood of seven patients who had an acute
      transient arthritis, putatively of viral origin. Viral DNA was detected in a
      synovial fluid sample and in the blood of one patient with monoarthritis who had
      an anti-B19 IgG response only. CONCLUSIONS: The prevalence of anti-B19 IgG
      antibody in these patients with various forms of arthritis (63%) was within the
      same range as that in the general population (blood donors). However, for the
      patients with clinical suspicion of viral arthritis, the increased seroprevalence
      of anti-B19 IgM and the presence of the B19 genome point to an association
      between human parvovirus infections and acute forms of arthritis.

PMID- 7632096
TI  - Activation of synovial fibroblasts in rheumatoid arthritis.

PMID- 7632097
TI  - Oxygen radicals, nitric oxide and human inflammatory joint disease.

PMID- 7632095
TI  - 2nd International meeting on synovium cell biology, physiology and pathology.
      Canterbury, United Kingdom, 21-23 September 1994. Proceedings and abstracts.

PMID- 7632098
TI  - Synovial membrane cellularity and vascularity.

PMID- 7632099
TI  - Synovial irritants: crystals, microbes and others--their implications for
      diagnosis, pathogenesis and therapy.

PMID- 7632101
TI  - Exposure to chemicals and systemic sclerosis.

PMID- 7632100
TI  - Therapeutic modulation of cytokines.

PMID- 7632102
TI  - Acquired sideroblastic anaemia associated with penicillamine therapy for
      rheumatoid arthritis.

PMID- 7632103
TI  - Homozygous complement factor deficiency and primary antiphospholipid syndrome: a
      clinical and serological study.

PMID- 7632104
TI  - Might patients with HLA-B27 related diseases benefit from antiandrogenic
      treatment?

PMID- 7632105
TI  - Asymmetric rheumatoid vasculitis in a hemiplegic patient.

PMID- 7632106
TI  - [Prospect of cardiac transplantation in Japan].

PMID- 7632107
TI  - [Posterior proctomucosectomy and ileal pull-through reconstruction: a new
      restorative procedure after total proctocolectomy].
AB  - We reported a new method of restorative proctocolectomy using posterior approach
      and pull-through reconstruction. This method obviated transanal manipulation, a
      major factor causing damage to the internal sphincter, thus preventing fecal
      incontinence due to sphincter dysfunction. Also, temporary ileostomy was not
      necessary because the spout of an S-pouch was pulled down below the anal verge
      and its distal free end acted as a diverting stoma while the more proximal,
      healing zone (future anastomotic line) was kept from fecal contamination. This
      method was applied to a 32-year-old woman with familial polyposis coli and a 50
      year-old woman with ulcerative colitis. Their bowel movements steadily decreased
      to three times and five times a day, respectively. There was no fecal leakage or
      perianal excoriation. The advantages as well as disadvantages of this method
      compared with the conventional techniques were discussed.

PMID- 7632108
TI  - [To avoid complications during laparoscopic cholecystectomy].
AB  - Laparoscopic cholecystectomy is now becoming a safe procedure for the benign
      cholecystic diseases. But the differences, for example in the method of access to
      peritoneal cavity, visual field, and tools, between laparoscopic surgery and open
      surgery results in different complications. The purpose of this paper is to
      discuss how to avoid complications during laparoscopic cholecystectomy. A hundred
      consecutive patients were expected to receive an elective laparoscopic
      cholecystectomy from April 1991 to November 1992 in our clinic. Two patients were
      converted to open cholecystectomy. The reasons for conversion were uncontrollable
      bleeding from cystic artery and common-bile duct injury. Two other patients were
      obliged to undergo laparotomy due to post-operative bile leakage. Arterial
      bleeding from abdominal wall caused by inserting trocar was experienced in one
      case. Improvement of the equipment and surgical technique have got rid of these
      complications. We think it is still necessary to do intra-operative examinations
      such as cholangiography or ultrasonography. The previous two cases with
      complication of biliary injury underwent laparoscopic cholecystectomy without
      intraoperative examinations. We could have avoided these complications if
      intraoperative examinations were used. To prevent the complication of bleeding
      from abdominal wall, we have been carrying out a unique method. After the
      introduction of these procedures, we have never experienced any of these
      complications.

PMID- 7632109
TI  - [Recurrent dislocation of the elbow].
AB  - A case of a recurrent dislocation of the elbow joint in a 13-year-old female is
      described. The patient sustained a medial epicondylar fracture of the humerus and
      consulted us four months later. There was no deformity but marked lateral
      instability of the elbow was recognized. It could be fully flexed and
      hyperextended ca 20 degrees. The elbow joint could be easily dislocated by
      pronation of the hyperextended elbow. Roentgenogram demonstrated an apparent non
      union of the medial epicondylar fracture. The fragment was repositioned so that
      the medial collateral ligament became taut. There was no recurrence of the
      dislocation ten months postoperatively.

PMID- 7632110
TI  - Role-relationship models for case formulation.
AB  - BACKGROUND: Personality disorders are important because they occur frequently and
      often complicate psychiatric symptom disorders. They are difficult to diagnose
      and formulate because unitary core traits and themes are hard to define for
      individual patients. A multiple-selves approach helps clinicians define core
      contradictions in belief that are frequently present. METHOD: A configurational
      system for case formulation was used with an approach of states and person
      schemas. Transactions and stories involving self and others were observed for
      recurrent elements of identity, attribution, and action. These elements were
      systematically arranged as role relationship models for each important state of
      behavior. Cyclic repetitions of maladaptive interpersonal behavior patterns were
      then explained in terms of motivations and social events that activate enduring,
      but erroneous, beliefs. RESULTS: Reliable and valid individualized formulations
      were derived by means of configurations of role relationship models. Inferring
      several levels of diverse self and other beliefs clarified the complexity usually
      found in disorders of personality. CONCLUSIONS: The role relationship models
      method of formulation is compatible with integrative approaches to treatment
      planning.

PMID- 7632111
TI  - Personality theory. Clinical practice, social development, and the biology of
      individual differences.

PMID- 7632112
TI  - Diagnosis, assessment, and individual complexity.

PMID- 7632113
TI  - Progress on case formulation.

PMID- 7632114
TI  - Between the past and the future of psychotherapy research.

PMID- 7632115
TI  - Are case formulations useful for outcomes research?

PMID- 7632116
TI  - Role-relationship models. Are they useful for research and practice?

PMID- 7632117
TI  - 'Richly complex' but needs an emotion theory.

PMID- 7632118
TI  - Personality: psychodynamic perspectives.

PMID- 7632119
TI  - Resting cerebral glucose metabolism in first-episode and previously treated
      patients with schizophrenia relates to clinical features.
AB  - BACKGROUND: Functional neuroimaging can elucidate brain dysfunction in
      schizophrenia. The frontal, temporolimbic, and diencephalic regions have been
      implicated. There is a lack of prospective samples of first-episode and
      previously treated patients followed up longitudinally. METHODS: Patients and
      controls (42 per group) were studied. Positron emission tomography with
      flurodeoxyglucose, cross-registered with magnetic resonance imaging, measured
      metabolism. Scales assessed clinical features, premorbid adjustment, and outcome.
      RESULTS: There were no differences between groups in whole-brain metabolism or
      regional ratios or in anterior-posterior gradients, but left midtemporal
      metabolism was relatively higher in patients. This was pronounced in the negative
      and Schneiderian and absent in the paranoid subtypes. Higher metabolism and lower
      relative left hemispheric values were associated with better premorbid adjustment
      and outcome. A higher subcortical-cortical gradient was noted in first-episode
      patients. CONCLUSIONS: There are no resting metabolic abnormalities in any brain
      region, but abnormal gradients are evident. These vary in subtypes, and
      laterality is associated with functioning. The results support the hypothesis of
      temporolimbic disturbance in schizophrenia that is all ready present at the onset
      of illness.

PMID- 7632121
TI  - Multiple-family groups and psychoeducation in the treatment of schizophrenia.
AB  - OBJECTIVE: To compare outcomes in psychoeducational multiple-family group
      treatment vs psychoeducational single-family treatment. METHOD: A total of 172
      acutely psychotic patients, aged 18 to 45 years, with DSM-III-R schizophrenic
      disorders were randomly assigned to single- or multiple-family psychoeducational
      treatment at six public hospitals in the state of New York. Psychotic relapse,
      symptom status, medication compliance, rehospitalization, and employment were
      assessed independently during 2 years of supervised treatment. RESULTS: The
      multiple-family groups yielded significantly lower 2-year cumulative relapse
      rates than did the single-family modality (16% vs 27%) and achieved markedly
      lower rates in patients whose conditions had not remitted at index hospital
      discharge (13% vs 33%). The relapse hazard ratio between treatments was 1:3. The
      relapse rate for both modalities was less than half the expected rate (65% to 80%
      for 2 years) for patients receiving individual treatment and medication.
      Rehospitalization rates and psychotic symptoms decreased significantly, and
      medication compliance was high, to an equal degree in both modalities.
      CONCLUSION: Psychoeducational multiple-family groups were more effective than
      single-family treatment in extending remission, especially in patients at higher
      risk for relapse, with a cost-benefit ratio of up to 1:34.

PMID- 7632120
TI  - Mitogen-stimulated interleukin-2 production in never-medicated, first-episode
      schizophrenic patients. The influence of age at onset and negative symptoms.
AB  - BACKGROUND: Decreased interleukin-2 (IL-2) production is characteristic of active
      autoimmune diseases and has previously been reported in patients with
      schizophrenia. We attempted to replicate this finding in never-medicated
      schizophrenic patients and examine the possible correlation between IL-2
      production and clinical variables. METHODS: The production of IL-2 was measured
      in equal numbers (N = 33) of DSM-III-R-diagnosed schizophrenic patients and
      controls who were matched for age, race, and gender. Patients were also assessed
      for positive, negative, and depressive symptoms. RESULTS: The production of IL-2
      was significantly lower in patients than in controls. There was a significant
      positive correlation between IL-2 production and age at onset, and significant
      negative correlation between IL-2 production and negative symptom scores. In
      multivariate analyses, the predictive power was stronger for age at onset than
      for negative symptoms. Positive or depressive symptoms were unrelated to IL-2
      production. CONCLUSIONS: Our finding of low IL-2 production in neuroleptic-native
      schizophrenic patients confirms that this finding is not confounded by
      medications. The correlation of low IL-2 production with younger age at onset
      suggests that this may be a marker for a subtype of the illness or for severity.

PMID- 7632122
TI  - Is hyperarousal essential to obsessive-compulsive disorder? Diminished
      physiologic flexibility, but not hyperarousal, characterizes patients with
      obsessive-compulsive disorder.
AB  - OBJECTIVE: To examine the hypothesis that the pathologic features of obsessive
      compulsive disorder (OCD) are facilitated by abnormal levels of arousal, we
      compared patients with OCD with controls on self-reports and psychophysiologic
      measures. METHODS: Twenty-three patients with OCD were compared with 21 controls
      on rating scales and on psychophysiologic measures (ie, heart interbeat interval,
      skin conductance, respiration, blood pressure, and electromyographic activity)
      during rest and during two psychologically stressful tasks. RESULTS: Patients
      rated themselves higher on psychic and somatic anxiety scales. Mean physiologic
      activities were not elevated at rest. During tasks, changes in electrodermal,
      cardiovascular (except blood pressure), and muscle activities were smaller in
      patients with OCD, indicating decreased physiologic flexibility. CONCLUSIONS:
      Hyperarousal, measured peripherally, is not an essential pathologic feature of
      OCD. Decreased physiologic flexibility indicates an anxiety-related, but not OCD
      specific, impairment of psychophysiologic reactivity to one's environment.

PMID- 7632123
TI  - Quality of care for depressed elderly patients hospitalized in the specialty
      psychiatric units or general medical wards.
AB  - BACKGROUND: Studies to assess quality of care have become increasingly important
      for research and policy purposes. OBJECTIVE: To evaluate the difference in
      quality of care between elderly depressed patients hospitalized in specialty
      psychiatric units and those hospitalized in general medical wards. METHODS: We
      reviewed retrospectively the medical charts of 2746 patients with depression
      hospitalized in 297 general medical hospitals in five different states. Quality
      of care was assessed by clinical review of explicit and implicit information
      contained in the medical records of patients in specialty psychiatric units (n =
      1295) and general medical wards (n = 1451). We also used other secondary data
      sources to determine postdischarge outcomes. RESULTS: We found that (1) a higher
      percentage of admissions on the psychiatric units were considered appropriate,
      (2) overall psychological assessment was better on the psychiatric unit, (3)
      patients were more likely to receive psychological services on the psychiatric
      wards but more likely to receive traditional general medical services on medical
      wards, (4) there were more inpatient general medical complications on the
      psychiatric wards, and (5) implicit measures of clinical status at discharge were
      better for those on the psychiatric unit. CONCLUSIONS: Although limited by
      reliance on medical record abstraction and a retrospective study design, our data
      indicate that the quality of care for the psychological aspects of the treatment
      of depression may be better on psychiatric units, while the quality of general
      medical components of care may be better on general medical wards.

PMID- 7632124
TI  - Functional scale discrimination at admission and discharge: Rasch analysis of the
      Level of Rehabilitation Scale-III.
AB  - OBJECTIVE: To determine the construct validity of the Level of Rehabilitation
      Scale-III (LORS-III) with a special focus on this instrument's capability to
      discriminate rehabilitation inpatient activities of daily living (ADL)/mobility
      and communication/cognition ability at admission and discharge. DESIGN: Rasch
      analysis of existing data sets in the LORS-III American Data System (LADS).
      PATIENTS: Existing admission and discharge data from 3056 rehabilitation
      inpatients (musculoskeletal injury, cerebrovascular accident, multiple
      injuries/diseases, brain injury, neuromuscular disorder, and spinal cord injury)
      entered into LADS between April 1992 and January 1993. MAIN OUTCOME MEASURE: LORS
      III consists of 17 measurement areas representing abilities in ADL, mobility,
      communication, cognition, and memory. Fourteen of the measurement areas are
      concurrently scored by a nurse and a specified rehabilitation therapist,
      resulting in a total of 31 items. RESULTS: Consistent with findings reported for
      other functional status measures, the analysis indicated that the LORS-III
      consists of two unidimensional scales, an ADL/mobility scale, and a
      communication/cognition scale. Although all scales fit the Rasch measurement
      model, the ADL/mobility scale used at admission was most appropriately targeted
      to the ability level of the sample. At discharge, the ADL scale was generally too
      easy because the ability level of the sample moved upward towards functional
      independence. The communication/cognition scale at both admission and discharge
      showed a similar "ceiling" effect. CONCLUSIONS: These findings indicate the
      importance of determining the measurement qualities of functional status measures
      for both admission and discharge ratings. Analyses, such as Rasch, can provide a
      logical direction for instrument refinement.

PMID- 7632125
TI  - Prediction of stroke volume during upper and lower body exercise in men and
      women.
AB  - In this study, regression equations were derived to predict cardiac stroke volume
      (SV, mL/beat), measured by carbon dioxide rebreathing, from oxygen pulse (O2
      pulse, mL/beat) measurements in healthy men (n = 25) and women (n = 12) during
      upper and lower body exercise at the ventilatory threshold. The equations for
      upper body exercise were as follows: men, Y = 10.21X - 1.0, SE = 13.0; r = 0.85;
      women, Y = 12.70X - 4.8, SE = 15.4, r = 0.78. The equations for lower body
      exercise were as follows: men, Y = 5.22X + 53.0, SE = 17.9, r = 0.76; women, Y =
      7.41X + 27.1, SE = 13.5, r = 0.78. No significant differences (p > .05) were
      observed between the exercise modes for the slopes and intercepts of the
      regression equations in both genders. The relationships between O2 pulse and SV
      were indirectly validated by using raw data from previous studies that had used
      the direct Fick method to determine cardiac output (Q) for each exercise mode and
      gender. Comparisons between the values of SV reported in several studies that
      used direct and indirect methods to determine Q and those predicted from the
      current equations indicated an error that was usually within 10% of the reported
      values. These observations suggest that the equations derived for predicting SV
      from O2 pulse measurements at the ventilatory threshold are quite accurate and
      can be generalized to a variety of techniques currently used to determine Q.

PMID- 7632126
TI  - Psychological measures: reliability in the assessment of stroke patients.
AB  - OBJECTIVE: To determine whether acute stroke patients can give reliable responses
      to standardized psychological measures. DESIGN: Survey design with retrospective
      review of Neurobehavioral Cognitive Status Examination (NCSE) scores. SETTING: A
      rehabilitation hospital in Philadelphia. PATIENTS: 106 consecutive admissions to
      stroke services at a rehabilitation hospital were evaluated according to the
      following inclusion criteria: Patients at least 65 years of age, English
      speaking, having a documented history of cerebrovascular accident (CVA),
      possession of receptive speech comprehension, and the ability to maintain
      attention adequate for participation in the study interview. Of the 47 eligible
      for participation, 10 patients refused participation and 13 were discharged
      before the interview could be completed. Thus 24 patients were interviewed, with
      one patient unable to complete the second half of the interview. MAIN OUTCOME
      MEASURES: In phase 1, the patient's performance on a structured interview
      (including the Multidimensional Health Locus of Control Scales (MHLC), Life
      Orientation Test (LOT), and Center for Epidemiological Studies Depression Scale
      (CES-D) scales) produced a Total Reliability Score, indicating the overall
      reliability of the patient's responses. In phase 2, NCSE scores were examined
      (retrospectively) for their ability to predict the patient's Total Reliability
      Score on the structured interview. RESULTS: Using Total Reliability Scores, 9
      patients were categorized as "passing," 9 were categorized as "uncertain," and 5
      were categorized as "failing" the interview. The NCSE was predictive for
      individuals who had a very low likelihood of being able to respond consistently.
      The NCSE failed to identify which individuals would respond in a reliable
      fashion. CONCLUSIONS: It is both possible and important to assess response
      reliability when using psychological measures soon after stroke. Future research
      will need to document other potential predictors of interview performance,
      including combinations of NCSE subscales.

PMID- 7632127
TI  - Visual tracking behavior in low functioning head-injured adults.
AB  - OBJECTIVE: To analyze visual tracking patterns of low functioning head-injured
      adults as follow-up to finding that visual tracking performance predicts
      rehabilitation-ready (RR) status. DESIGN: Case series of patients in a 4-year
      study of predictors of early cognitive improvement. SETTING: Private subacute
      care facility providing sensory stimulation and slowly paced rehabilitation.
      PATIENTS: Convenience sample of 76 subjects: 45 achieved RR status; 31 did not
      (NRR). Men = 54; Women = 22. Age at injury: 12 to 73 years (median [Md] = 27).
      Time postinjury at initial assessment: 25 to 365 days (Md = 57). Cognitive status
      at initial assessment: Western Neuro Sensory Stimulation Profile (WNSSP) Score
      below 47. INTERVENTION: Subjects assessed by WNSSP Visual Tracking subscale
      (VISTRACK) at admission and every 2 weeks thereafter for 2 to 48 months
      postinjury. MAIN OUTCOME MEASURES: VISTRACK scores for Direction (horizontal vs
      vertical) and Stimulus (mirror, individual, picture, object) analyzed
      quantitatively and qualitatively at admission and longitudinally. RESULTS: RR
      subjects showed significantly higher scores at admission when tracking face in
      mirror versus other stimuli. No differences were observed for NRR subjects. No
      statistical differences seen for direction of tracking for either group, but 48%
      of subjects showed preference for tracking in one direction versus the other at
      initial assessment. CONCLUSIONS: Visual tracking not a unitary phenomenon but
      dependent on stimulus and direction. RR subjects' ability to track their own face
      in mirror seems to be critical variable in predictive value of VISTRACK subscale.
      Potency of human face as stimulus relates to developmental and neurophysiological
      factors. Awareness of effects of stimulus and direction on tracking function
      warrants comprehensive visual tracking assessment.

PMID- 7632128
TI  - Normal concentrations of serum insulin-like growth factor-1 in late polio.
AB  - A recent study of 10 men with postpolio syndrome indicated a low secretion of
      growth hormone (GH) as reflected by serum insulin-like growth factor-I (IGF-1).
      Therefore, 87 patients were studied, 17 to 71 years after acute poliomyelitis, of
      whom 65% reported the occurrence of new or increased weakness (ie, during the
      last 2 years) in muscles previously affected by polio. Serum IGF-1 concentrations
      in the patients were compared with those found in a reference population
      comprising 392 randomly selected individuals. No differences from the reference
      population values were observed. No correlation was found between IGF-1
      concentrations and the severity of the original polio affliction, the recovery
      status, the need for ambulation aids, or the presence of new symptoms. The
      results do not indicate a need for GH substitution treatment of patients with
      postpolio syndrome.

PMID- 7632129
TI  - Prosthetic gait of unilateral transfemoral amputees: a kinematic study.
AB  - OBJECTIVE: The prosthetic gait of unilateral transfemoral amputees. DESIGN: Case
      series. SETTING: Laboratory of Gait Analysis (GIGA-system of K-lab) in the
      Department of Rehabilitation of a university hospital. PATIENTS: Eleven men with
      transfemoral amputation (mean age 35.7 years) participated. The amputation was
      performed at least 2 years ago and was caused by trauma or osteosarcoma. MAIN
      OUTCOME MEASURES: Stride parameters as well as the patterns of motion of the
      trunk, hip, and knee joint. RESULTS: The amputees walked with a 29% lower vcomf
      than normal subjects. The amputees compensate the vrapid with their stride length
      rather than with their step rate. The amputees showed an asymmetrical walking
      pattern; the amputees stood a little longer on their intact leg than on their
      prosthetic leg. Four amputees showed an extreme lateral bending of the trunk
      toward the prosthetic side during the stance phase of the prosthetic leg. The
      rebound of the hip at the amputated side at heel strike was very small or absent.
      The intact knee was flexed at heel strike and remained in a flexed position
      during the entire stance phase. CONCLUSIONS: The amount of asymmetry of the
      walking pattern is related to the stump length. The amputees with highly
      atrophied hip-stabilizing muscles walked with an extreme lateral bending of the
      trunk toward the prosthetic side. There is no correlation between stride width
      and lateral bending of the trunk. Amputees with a short and medium stump length
      showed a fast transition from hip extension to hip flexion.

PMID- 7632130
TI  - Intermittent pneumatic compression effect on eccentric exercise-induced swelling,
      stiffness, and strength loss.
AB  - OBJECTIVE: The purpose was to determine if intermittent pneumatic compression
      (IPC) affects muscle swelling, stiffness, and strength loss resulting from
      eccentric exercise-induced injury of the elbow flexors. We hypothesized that the
      compression would decrease swelling and stiffness. DESIGN: Repeated measures
      design with a before-after trial comparison within each day. SETTING: Conducted
      at a university Somatic Dysfunction Laboratory. SUBJECTS: Twenty-two college
      women students were studied. They had not been lifting weights or otherwise
      participating in regular arm exercise for the 6 months before the study. They had
      no history of upper extremity injury or cardiovascular disease. INTERVENTIONS:
      Subjects performed one bout of eccentric exercise at a high load to induce elbow
      flexor muscle injury. Uniform IPC was applied on the day of exercise and daily
      for 5 days at 60mmHg, 40 seconds inflation, 20 deflation for 20 minutes. MAIN
      OUTCOME MEASURES: Measurements of arm circumference, stiffness, and isometric
      strength were recorded before exercise, then before and after IPC for 5 days
      after exercise. Passive muscle stiffness was measured on a device that extends
      the elbow stepwise and records the torque required to hold the forearm at each
      elbow angle. RESULTS: Circumference and stiffness increased and strength
      decreased during the 5 days post-exercise (p < .05). IPC significantly decreased
      circumference and stiffness most notably on days 2 and 3 after exercise (p <
      .05). The strength loss was not affected by IPC. CONCLUSION: IPC is effective in
      temporarily decreasing the swelling and stiffness after exercise-induced muscle
      injury.

PMID- 7632131
TI  - Selective muscle activation following electrical stimulation of the collateral
      ligaments of the human knee joint.
AB  - The objective of this study was to establish the presence of a local neurosensory
      reflex are from mechanoreceptors in human collateral ligaments and joint capsule
      to knee muscles and to determine if these muscles could be selectively activated
      as varus or valgus stabilizers using randomized trials. All studies were
      performed in the research department laboratories. Eleven subjects were recruited
      from the university staff and students based on no prior history of knee
      ailments. Subjects laid supine on an experimentation table as a current-modulated
      electrical stimulation was provided through the medial (MCL) or lateral
      collateral (LCL) knee ligaments. Latency of activation was measured for seven
      muscles, four by surface electrodes (semitendinosus, biceps femoris long head,
      vastus medialis, and lateralis), and three by intramuscular electrodes
      (sartorius, gracilis, tensor fascia lata). In the protocol, selective activation
      was defined as the relative increase in the activity of four muscles with medial
      moment arms following MCL stimulation compared with corresponding activity
      following LCL stimulation. For lateral muscles, the opposite was assumed (ie,
      that more activity would follow LCL than MCL stimulation). Monte Carlo
      simulations were performed on the data to determine significant selective muscle
      activation (p < .05). Statistically significant increases in activation were
      observed, most consistently, in the vastus medialis following MCL stimulation and
      in the vastus lateralis following LCL stimulation. These results suggest that a
      neurosensory reflex are from ligament mechanoreceptors may provide varus and
      valgus stabilization and knee muscles may be selectively activated to counter
      varus or valgus loads.

PMID- 7632132
TI  - Improved quality of life and sexuality with continent urinary diversion in
      quadriplegic women with umbilical stoma.
AB  - Quality of life issues prompted us to offer continent urinary diversion to
      quadriplegic women who required cystectomy for end-stage neurogenic vesical
      dysfunction complicated by urethral destruction as a result of chronic indwelling
      catheterization. Three women with spinal cord injury (SCI) and resultant
      quadriplegia of 5 to 15 years duration underwent continent urinary diversion.
      Preoperative evaluation and urodynamic studies in each showed a bladder capacity
      of less than 150mL, bilateral vesicoureteral reflux, recurrent febrile urinary
      tract infections, an incompetent urethral sphincter, and incontinence around an
      indwelling catheter in all three patients. Although highly motivated, these women
      showed minimal dexterity and were unable to perform urethral self
      catheterization. Each was opposed to having an incontinent abdominal urinary
      stoma. The urinary reservoir was created from 30cm of detubularized right colon.
      The continence mechanism used an intussuscepted and imbricated ileocecal valve.
      The umbilicus was chosen as the urostomy site because of cosmetic appearance and
      ease of catheterization for a patient with minimal dexterity. Follow-up ranged
      from 18 to 30 months. Reservoir capacity ranged from 550 to 800mL without
      evidence of reflux or stomal leakage. The incidence of symptomatic autonomic
      dysreflexia and urinary tract infection decreased postoperatively in all
      patients. Of the two women who were sexually active, the frequency of activity
      increased from 8 to 15 episodes per month in one and 3 to 4 episodes per month in
      the other. Both reported improved sexual enjoyment. Body image and satisfaction
      with urologic management increased in all three patients. In conclusion,
      continent urinary diversion in selected quadriplegic patients is a reasonable
      alterative to incontinent intestinal urinary diversion. The umbilical stoma
      provides an excellent cosmetic result which patients with minimal dexterity are
      able to catheterize easily. Continent urinary diversion in women results in
      improved self-image, quality of life, and enables greater sexual satisfaction.

PMID- 7632133
TI  - Shoulder subluxation after stroke: a comparison of four supports.
AB  - OBJECTIVE: Shoulder subluxation is a well-known sequela of stroke. This study
      quantitatively compares the reduction of shoulder subluxation using four
      supports: the single-strap hemisling, the Bobath roll, the Rolyan humeral cuff
      sling, and the Cavalier support. DESIGN/SETTING: Anteroposterior shoulder
      radiographs of 20 consecutive first-time stroke survivors in a freestanding
      rehabilitation hospital were taken within 6 weeks of stroke onset. Vertical,
      horizontal, and total asymmetries of glenohumeral subluxation compared with the
      unaffected shoulders were measured before and after fitting of each support. MAIN
      OUTCOME MEASURES: Group means were compared to find which supports altered
      subluxation asymmetries and approximated the unaffected shoulder. Individual data
      were tallied to detect how often each support best reduced subluxation
      asymmetries. RESULTS: The single-strap hemisling eliminated the vertical
      asymmetry of subluxation over the entire study group, but each support corrected
      the vertical asymmetry best in some subjects (55%, 20%, 40%, and 5%,
      respectively). The Bobath roll and the Cavalier support produced lateral
      displacements of the humeral head of the affected shoulder (p = 0.005, 0.004,
      respectively). The Rolyan humeral cuff sling significantly reduced total
      subluxation asymmetry (p = 0.008), whereas the single-strap hemisling, Bobath
      roll, and Cavalier support did not alter total asymmetry (p = 0.091, 0.283,
      0.502, respectively). CONCLUSION: When treating shoulder subluxation, several
      different types of supports should be evaluated to optimize the function of the
      affected extremity and the reduction of the shoulder subluxation.

PMID- 7632134
TI  - A treadmill apparatus and harness support for evaluation and rehabilitation of
      gait.
AB  - This report describes a treadmill apparatus for the evaluation and rehabilitation
      of gait in disabled persons. The apparatus incorporates a body weight support
      system as well as mechanisms to change certain conditions: treadmill belt speed,
      upward-downward and lateral slopes, and provision of obstacles. The apparatus
      enables elements of a treadmill walking pattern to be visible in persons for whom
      gait evaluation or rehabilitation may not otherwise be possible. It also allows
      for exploration of factors that limit the adaptability of gait in person after
      disease or injury by changing the mechanical demand of the locomotor task.

PMID- 7632135
TI  - The reciprocating gait orthosis: long-term usage patterns.
AB  - OBJECTIVE: To investigate the frequency of nonusage of the reciprocating gait
      orthosis (RGO) in 85 patients supplied between 1986 and 1993. Reasons for
      nonusage and usage patterns were examined. DESIGN: Nonusage was determined from
      patient records and clinical knowledge. Patients were surveyed using a detailed
      questionnaire to produce information on usage patterns. SETTING: All patients had
      been treated as hospital outpatients. PATIENTS: Most patients had congenital or
      acquired spinal cord lesions. Postal questionnaires were sent to 81 patients 5 to
      55 years of age (mean 20.4 years). Thirty-five patients replied. RESULTS: At a
      mean follow-up of 5.4 years, 71% of patients were classified as nonusers. Of the
      35 respondents to the questionnaire (mean follow-up 5.5 years, range 4 to 7
      years), 20 patients were nonusers. Median usage was 27 months in patients under
      age 18 and 24 months in adult patients. Significant differences were observed
      between nonusers and users in the areas of perception of the RGO as a functional
      tool, independence, and reliability and between the adult and the under 18 groups
      in the areas of weekly usage, function, independence, and reliability.
      CONCLUSION: The high level of nonusage of the RGO has implications for
      prescription practice. Identifying reasons for nonusage and acknowledging
      differences in use between age groups will help in patient assessment.

PMID- 7632136
TI  - Statistical guidelines for the Archives of PM&R. New Hampshire-Dartmouth
      Psychiatric Research Center.

PMID- 7632137
TI  - Dysphagia screening test.

PMID- 7632138
TI  - Stroke patients and walking.

PMID- 7632139
TI  - Exploring molecular biology. An older surgeon looks at a new universe.
AB  - The rapidity and the magnitude of progress in molecular biology slipped by many
      of us practicing surgeons. Although articles about molecular medicine appear
      regularly in our surgical literature, for many of us, their content is rather
      mysterious. The articles often end with a glossary, because most readers do not
      understand the language. In November 1993, the entire issue of the Archives of
      Surgery was devoted to molecular medicine. In an editorial, Claude Organ, Jr, MD,
      a member of this association, encouraged the surgeon to "cohabit" with the
      molecular scientist. Many university departments of surgery have professors who
      are both surgeons and molecular biologists. Ed Passaro, MD, also a member of this
      association, observed in 1992 that most surgeons had overlooked this new field
      and needed to learn about it to play a role in applying it to clinical medicine.
      That means knowing what new tests and treatments are available and how to apply
      them. It means being able to counsel patients. Also, it is important for
      knowledgeable surgeons to serve on the regular hospital committees that will
      oversee these new tests and treatments, and to offer their unique judgment in
      assessing risk, reward, and ethical implications.

PMID- 7632140
TI  - Gastrointestinal and pancreatic complications associated with severe
      pancreatitis.
AB  - OBJECTIVE: To study the outcomes of gastrointestinal fistulas and pancreatic
      ductal disruption in severe pancreatitis. SETTING: University tertiary referral
      center. PATIENTS: One hundred thirty-six patients from 1982 to 1994.
      INTERVENTION: Diversion followed by resection and ostomy closure for
      gastrointestinal fistulas, pancreaticojejunostomy for pancreatic fistulas, and
      excision, external drainage, or internal drainage for pseudocysts. RESULTS: The
      incidence of infection was 24% (8/33) for peripancreatic fluid collections and
      59% (61/103) for patients with necrosis plus fluid collections or necrosis
      without fluid. Sixty-nine patients developed 25 gastrointestinal fistulas and 51
      complications caused by pancreatic ductal disruption. Necrosis and infection but
      not the open packing technique were associated with increased risk of
      gastrointestinal fistulas. In patients with pancreatic ductal disruption,
      pancreatic fistulas developed following necrosectomy and external drainage, while
      pancreatic pseudocysts evolved from undrained peripancreatic fluid collections.
      Gastrointestinal fistulas required prompt operative intervention, whereas
      pancreatic ductal disruption was treated nonoperatively initially. The mortality
      rate was 13% (3/23) in patients with gastrointestinal fistulas, similar to the
      overall mortality rate of 10.3% (14/136). There was no mortality in patients with
      pancreatic fistulas or pseudocysts. Length of hospital stay was prolonged by the
      presence of necrosis and infection, not by gastrointestinal fistulas or ductal
      disruption. Thirty-eight of the 69 patients with these complications required
      readmission for operative management of their complications. To date, only 18
      (13.2%) of 136 patients with severe pancreatitis have not required surgical
      intervention. CONCLUSIONS: Gastrointestinal fistulas and pancreatic ductal
      disruption are common in severe pancreatitis. Although these complications are
      not associated with increased mortality or prolonged initial length of stay,
      readmission for elective surgical correction is necessary in most patients.
      Severe pancreatitis is a surgical disease, requiring both acute and long-term
      surgical care.

PMID- 7632142
TI  - Bowel obstruction in cancer patients.
AB  - OBJECTIVE: To examine the efficacy of various interventions on bowel obstruction
      occurring in patients with a history of cancer. DESIGN: Retrospective case
      series. SETTING: A university comprehensive cancer center. PATIENTS: Sixty-one
      patients presenting with 81 episodes of intestinal obstruction. RESULTS: Sixty
      nine episodes of obstruction affected the small bowel, including 24 complete
      obstructions. There were 12 episodes of large-bowel obstruction, eight of which
      were complete. Five patients (8.2%) had concurrent small- and large-bowel
      obstruction. In 59 cases, the cause was established: 36 (61%) were due to
      metastatic tumor and 23 (39%) were due to benign conditions. Of the 49 episodes
      of partial bowel obstruction, 42 (86%) initially were treated medically. Nineteen
      (45%) of these 42 cases of obstruction resolved after 8.7 +/- 11.1 days (mean +/-
      SD) of conservative management. Twenty-two patients with partial obstruction were
      treated surgically, with relief of obstruction in 15 cases (68%). Of the 32
      episodes of complete obstruction, 26 (81%) were initially managed conservatively;
      in only one case (3.8%) did obstruction resolve. Surgery successfully relieved
      the obstruction in 16 (76%) of 21 patients. Twenty-six patients received
      parenteral nutrition at home as the major treatment for obstruction; 22 (85%)
      experienced relief of nausea and vomiting. Patients with malignant obstructions
      survived 0 to 24 months (median, 4.7 months); the median survival for those
      treated surgically was 5.0 months. CONCLUSIONS: In patients with a history of
      cancer, partial obstruction (but not complete obstruction) frequently resolves
      with medical management. Surgical intervention relieves most cases of partial or
      complete obstruction regardless of benign or malignant cause, but survival often
      is limited in the latter group. The entire intestinal tract should be evaluated
      in all patients, since 8.2% of patients in this series had concurrent small- and
      large-bowel obstructions. Home parenteral nutrition often provides symptomatic
      palliation in patients not amenable to surgical relief.

PMID- 7632141
TI  - Total vascular exclusion for major hepatectomy in patients with abnormal liver
      parenchyma.
AB  - BACKGROUND: Total vascular exclusion (TVE) of the liver has been used to increase
      the safety of hepatectomy and the feasibility of difficult resections. Until
      recently, however, concern about the detrimental effect of warm ischemia has
      limited the use of this technique to patients with normal liver parenchyma.
      OBJECTIVE: To compare surgical outcomes of 12 patients with abnormal livers
      (group 1) with outcomes of 48 patients with normal parenchyma (group 2), based on
      the hypothesis that uncontrolled bleeding may be more detrimental than planned
      hepatic ischemia. DESIGN AND SETTING: Retrospective analysis of 60 consecutive
      patients undergoing liver resection under TVE in a university medical center.
      PATIENTS: All 10 patients with cirrhosis had albumin levels of 30 g/L or higher
      and normal prothrombin times preoperatively; none had ascites. Two patients with
      cholestasis (one with cholangiocarcinoma and one with hepatocellular carcinoma)
      are included in group 1. INTERVENTION: All 12 group 1 patients and 44 of 48 group
      2 patients underwent total or extended lobectomy, with TVE induced by clamping
      the hilum and the vena cava above and below the liver during parenchyma division.
      MAIN OUTCOME MEASURES: Hospital survival and selected surgical and laboratory
      parameters. RESULTS: Operative times, ischemic times, and blood loss (1975 +/-
      1601 vs 1255 +/- 1291 mL) (P = .10) were comparable in both groups. Sixty-day
      operative mortality was zero in both groups. There was an increased rate of
      complications in group 1 (44% vs 17% [P = 0.06]). Transient abnormal liver
      function was observed in both groups. However, significant delay in restoration
      of normal function was observed in group 1 with respect to bilirubin levels and
      prothrombin time. CONCLUSIONS: Patients with cirrhosis can undergo successful
      resection using TVE. This conclusion must be limited to cirrhotic patients with
      good liver function. The trend toward increased blood loss may reflect greater
      difficulties in establishing hemostasis after reperfusion in group 1. While this
      group appears to have a higher risk for hepatic insufficiency, successful
      outcomes were achieved in all cases. Prospective study will be required to define
      the parameters for use of TVE in cirrhosis.

PMID- 7632143
TI  - Pylorus-preserving Whipple resection for pancreatic cancer. Is it any better?
AB  - OBJECTIVE: To compare the short- and long-term morbidity and mortality rates of
      the standard Whipple pancreatoduodenectomy (SW) and its pylorus-preserving
      modification (PPW) in patients with malignant periampullary disease. DESIGN:
      Retrospective medical record review and quality of life assessment by telephone
      interview. SETTING: University medical center. STUDY PARTICIPANTS: Sixty-seven
      patients who underwent pancreatoduodenectomy (52 SW and 15 PPW) from June 1988 to
      January 1994. INTERVENTION: The SW and PPW. MAIN OUTCOME MEASURES: Operative
      features and short- and long-term complications were analyzed with respect to the
      type and stage of cancer and the kind of pancreatic resection. Mean follow-up was
      32 months (range, 1 to 5 years). RESULTS: The operative mortality rate for all
      patients who had a pancreatic resection was 1.5%. The diagnoses in the PPW vs SW
      groups were pancreatic cancer (four vs 27 patients), ampullary cancer (six vs
      seven patients), duodenal cancer (zero vs six patients), and bile duct cancer
      (five vs one patient). Operative mortality rates (0% vs 1.55%) and operative
      times (2 minutes longer for SW) were similar. Delayed gastric emptying (61% vs
      41%) was more common in the PPW group, resulting in a longer hospitalization (24
      vs 18 days) and a greater cost in the PPW group (P = .04). In the PPW group, a
      mean of five lymph nodes was removed compared with 10 in the SW group (P = .04).
      CONCLUSIONS: The data provided no evidence of any advantage for the PPW in
      patients with malignant periampullary tumors. We continue to advocate the SW for
      pancreatic cancer.

PMID- 7632144
TI  - High-risk behavior and the public burden for funding the costs of acute injury.
AB  - OBJECTIVE: To determine if high-risk behavior is associated with increased injury
      severity and cost and if public agencies bear a disproportionate burden of that
      cost. DESIGN: Case comparison study utilizing patient data collected over a 10
      year period. SETTING: Five level 1 and 2 trauma centers in an urban-suburban
      community with a population of 2.4 million. PARTICIPANTS: Trauma registry data
      from 37,304 consecutive hospitalized adult patients with trauma. Financial data
      were reported and analyzed on 28,842 of these. MAIN OUTCOME MEASURES: Incidence
      of alcohol intoxication, other drug use, use of vehicular protective devices, and
      firearm violence injuries in patients with private vs public health care
      sponsorship. Length of hospital stay, injury severity, and hospital unit charges
      were assessed for high-risk behavior. RESULTS: High-risk behavior was more
      prevalent among trauma patients relying on public funding to cover the costs of
      their injuries (P < .001). Total hospital unit charges were 28% and 35% higher
      for motorists not wearing seat belts and motorcyclists not wearing helmets,
      respectively. Injury severity and length of stay were also higher (P < .001).
      CONCLUSIONS: High-risk behavior is associated with increased injury severity and
      cost. Trauma victims exhibiting high-risk behavior more often depend on public
      agencies to cover the cost of acute injury. Failure to establish and enforce laws
      and policies designed to reduce or prevent injury may generate enormous trauma
      care costs, borne to a large extent by public agencies. Further restriction of
      certain types of high-risk behavior and the institution of "users' fees," taxes,
      or penalties may be necessary to reduce the disproportionate public agency cost
      generated by this activity.

PMID- 7632145
TI  - Blunt cardiac rupture. The Emanuel Trauma Center experience.
AB  - OBJECTIVE: To analyze the factors affecting outcome in patients with blunt
      cardiac rupture, including anatomical cardiac injury, associated injury, clinical
      presentation, age, mechanism of injury, diagnostic method, surgical intervention,
      and presence of vital signs in the field and on arrival. DESIGN: Retrospective
      review. SETTING: A community-based level I trauma center. PATIENTS: A consecutive
      series of 27 patients seen between 1984 and 1993. MAIN OUTCOME MEASURE: Survival
      with return to preinjury activity. RESULTS: Eleven patients (41%) survived
      resuscitation, surgery, and initial hospital care. Survivors had a lower mean
      Injury Severity Score (38) than nonsurvivors (62) (P < .05). Three (33%) of nine
      patients who arrived with no blood pressure or viable electrical heart rhythm
      survived. No patient survived rupture of two cardiac chambers. CONCLUSIONS:
      Patients with blunt cardiac rupture who present with cardiac arrest can survive.
      Nonsurvivors tend to have more associated injuries, as indicated by higher Injury
      Severity Scores. Our institution's overall survival rate of 41% (11/27) compares
      favorably with rates at other trauma centers.

PMID- 7632146
TI  - Arterial anatomic considerations in colon interposition for esophageal
      replacement.
AB  - BACKGROUND: Little has been written regarding the arterial anatomy predictive of
      success following esophagectomy and colon interposition. DESIGN: Retrospective
      review. SETTING: University teaching hospital. PATIENTS: Twenty-five patients
      undergoing planned left colon interposition. INTERVENTION: Colon interposition
      was performed via an isoperistaltic left colon graft based on the ascending
      branch of the left colic artery. MAIN OUTCOME MEASURES: Five angiographic
      features were considered important to successful use of the left colon: (1) a
      patient inferior mesenteric artery, (2) a visible ascending branch of the left
      colic artery, (3) a well-defined anastomosis between the middle colic and left
      colic systems, (4) a single middle colic trunk prior to its division into right
      and left branches, and (5) a separate origin of the right colic artery. Venous
      drainage via a patent marginal vein, inferior mesenteric vein, and superior
      hemorrhoidal veins was preserved in all patients. RESULTS: Left colon
      interposition could be performed in 21 (84%) of 25 patients. Eighty percent of
      the patients (20/25) had at least four of the five criteria thought necessary for
      optimal graft perfusion. Three or fewer criteria were present in five patients,
      three of whom underwent gastric interposition. The inferior mesenteric artery was
      patent in all patients except one who required a right colon interposition.
      Ninety-two percent (23/25) demonstrated an adequate ascending left colic artery.
      The superior-inferior mesenteric artery anastomosis was seen in 52% (13/25). A
      single-trunked middle colic artery was present 80% (20/25) of the time. A single
      incidence of graft necrosis occurred secondary to venous insufficiency. Ninety
      six percent of patients (24/25) were able to swallow without difficulty at the
      time of discharge from the hospital. CONCLUSIONS: Replacement of the esophagus
      with colon can be successful in over 80% of patients screened by angiographic
      criteria. Patients with an occluded or stenotic inferior mesenteric artery or
      variant middle colic arterial anatomy should undergo an alternate reconstruction.

PMID- 7632147
TI  - Effect of dopamine on renal blood flow and cardiac output.
AB  - OBJECTIVE: To characterize the relationship between changes in renal blood flow
      and cardiac output induced by dopamine, hypothesizing that at low doses renal
      blood flow changes more than cardiac output. DESIGN: Anesthetized swine had renal
      blood flow and cardiac output measured during either continuous dopamine
      infusions (2 to 8 micrograms/kg per minute) or bolus dosing (1 to 16
      micrograms/kg), and increases in both were compared. Two different fluid
      protocols were compared using constant dopamine infusions. In the constant
      pulmonary capillary wedge pressure protocol, intravenous fluids were titrated to
      keep this parameter constant. In the other protocol, fluid therapy was held
      constant at 10 mL/kg per hour. RESULTS: With infusions, mean increases in renal
      blood flow and cardiac output were relatively equal. The maximum increase was 35%
      at 8 micrograms/kg per minute under the constant pulmonary capillary wedge
      pressure protocol, with no significant differences (P > .1) found between the
      change in renal blood flow and cardiac output at any dose in either protocol.
      With bolus dosing, renal blood flow increased significantly more than cardiac
      output at 1, 4, and 8 micrograms/kg (P < .05). CONCLUSION: Disproportionate
      increases in renal blood flow compared with cardiac output at low bolus doses
      show initial renal responses to be independent of cardiac output. The infusion
      data suggest that renal responses exhibit tachyphylaxis or that cardiac output
      slowly accommodates to decreased total peripheral resistance.

PMID- 7632148
TI  - Reducing perioperative myocardial infarction following vascular surgery. The
      potential role of beta-blockade.
AB  - OBJECTIVE: To determine which perioperative variables may influence the
      occurrence of perioperative myocardial infarction (PMI) following vascular
      surgery. DESIGN: Case-control study. SETTING: Combined Veterans Affairs Medical
      Center-university hospital vascular service. PATIENTS: During a 4-year period,
      all major vascular surgical operations (N = 2088) were evaluated with serial
      postoperative electrocardiography and cardiac enzyme measurements. Patients with
      PMI following nonemergent vascular surgery (N = 53) were matched with randomly
      selected control patients without PMI (N = 106) for age, gender, type of
      operation, hypertension, and symptoms of coronary artery disease. MAIN OUTCOME
      MEASURES: The two groups were compared for operative blood loss, blood pressure,
      and heart rate as well as length of operation, type of anesthetic, and use of
      perioperative beta-blockers, nitroglycerine, calcium channel blockers,
      vasopressors, and angiotensin-converting enzyme inhibitors. RESULTS: beta
      Blockers were used less frequently in patients with PMI than in control patients
      without PMI (30% vs 50%; P = .01). Overall beta-blockade was associated with a
      50% reduction in PMI (P = .03). Perioperative myocardial infarction was not
      associated with length of operation, type of anesthetic, blood pressure, or use
      of other medications. CONCLUSIONS: beta-Blockade is associated with a decreased
      incidence of PMI in patients undergoing vascular surgery. Prophylactic
      perioperative use of beta-blockers may decrease PMI in patients requiring major
      vascular surgery. A prospective randomized trial of beta-blockers in these
      patients appears to be warranted.

PMID- 7632149
TI  - Laparoscopic splenectomy. The initial experience at University of California, San
      Francisco.
AB  - OBJECTIVE: To evaluate the outcomes of patients undergoing laparoscopic
      splenectomy (LS) at a single institution. DESIGN: Case control. SETTING:
      University teaching hospital. PATIENTS: The medical records of the initial 25
      consecutive patients who underwent LS at a single institution were reviewed. For
      comparison, a control group of 25 patients undergoing open splenectomy (OS)
      matched for age, diagnosis, and splenic weight were also reviewed. MAIN OUTCOME
      MEASURES: Data regarding operative time, blood loss, pathologic findings,
      complications, postoperative hospital stay, ileus duration, preoperative and
      postoperative hematocrit and platelet counts, blood and platelet transfusions,
      and hospital costs were collected. RESULTS: Twenty-five patients underwent
      attempted LS. Four procedures (16%) were converted to OS. Operative time averaged
      3.3 +/- 0.2 hours for LS and 2.6 +/- 0.1 hours for OS (P = .001). In the LS
      group, a regular diet was tolerated 2.1 +/- 0.3 days after surgery (P < .001),
      and mean postoperative hospital stay was 5.1 +/- 0.6 days (P = .037), compared
      with 4.3 +/- 0.3 and 6.7 +/- 0.5 days, respectively, in the OS group. No
      differences were observed in blood loss, complication rate, transfusion
      requirement, or hospital cost. CONCLUSIONS: Compared with OS, LS requires more
      operative time, is comparable in blood loss, transfusion requirement,
      complication rate, and cost, and appears to be superior in terms of return of
      bowel function and hospital stay.

PMID- 7632150
TI  - Bile duct stones in the laparoscopic era. Is preoperative sphincterotomy
      necessary?
AB  - OBJECTIVE: To evaluate treatments for common bile duct stones (CBDS). DESIGN:
      Retrospective review of authors' case series. SETTING: Large private metropolitan
      teaching hospital. PATIENTS: All patients with CBDS (N = 145) from a series of
      1231 patients who underwent laparoscopic cholecystectomy, 99% with intraoperative
      fluorocholangiography. INTERVENTIONS: Treatments for CBDS included one or more of
      the following: laparoscopic transcystic duct exploration (n = 123), laparoscopic
      choledochotomy (n = 10), open choledochotomy (n = 7), preoperative endoscopic
      sphincterotomy (ES) (n = 9), intraoperative ES (n = 2), post-operative ES (n =
      11), or observation (n = 10). MAIN OUTCOME MEASURES: Success of various
      interventions for CBDS, morbidity and mortality, frequency of retained stones,
      operative time, and length of postoperative hospitalization. RESULTS:
      Laparoscopic transcystic duct exploration was successful in 91% of attempts and
      resulted in the shortest postoperative stay (3.4 days), least morbidity (5%), and
      fewest retained stones (5%). Endoscopic sphincterotomy was successful in 56% of
      preoperative attempts, 50% of intraoperative attempts, and 91% of postoperative
      attempts. There were no reoperations and one death. CONCLUSIONS: For patients
      requiring cholecystectomy, laparoscopic transcystic duct exploration is safe and
      effective, treats CBDS in one session, and if unsuccessful still allows for open
      choledochotomy or postoperative ES. Preoperative endoscopic retrograde
      cholangiography and ES should be reserved for patients with serious illness or
      possible malignant disease.

PMID- 7632151
TI  - Carotid endarterectomy with shortened hospital stay.
AB  - OBJECTIVE: To review the outcome of a consecutive series of patients undergoing
      carotid endarterectomy with a focus on length of stay. DESIGN: Retrospective case
      review. SETTING: Six hundred-bed community hospital. PATIENTS: During a 40-month
      period, we performed 266 carotid endarterectomies. Ages of patients ranged from
      49 to 91 years (mean, 71.2 years). Seventy-two percent were hypertensive, 55%
      were smokers, 24% were diabetic, and 22% had symptomatic heart disease.
      Indications for operation included asymptomatic stenosis in 48% of patients,
      transient ischemia attack in 23%, stroke in 24%, and nonhemispheric symptoms in
      5%. OUTCOME MEASURES: Perioperative complications and conditions precluding early
      hospital discharge were noted. In patients discharged within 48 hours of
      operation, problems requiring readmission within 30 days were recorded. RESULTS:
      Five patients (1.9%) experienced perioperative strokes, of which three were
      permanent and two temporary. There was one perioperative death. Hospital stays
      ranged from 1 to 9 days (mean 1.7 days). Sixty-three percent of the patients were
      discharged within 24 hours and 88% within 48 hours of operation. Patients staying
      in the hospital more than 48 hours were significantly older (P = .008). Other
      factors did not correlate with length of stay. Readmission was required in five
      patients. CONCLUSIONS: Patients having an uneventful course following carotid
      endarterectomy may be safely discharged within 48 hours of operation.
      Complications occurring after this time are infrequent and often unpredictable.
      It is unlikely that lengthening patient stay would decrease or eliminate these
      complications.

PMID- 7632153
TI  - Prevalence of asymptomatic carotid stenosis in patients undergoing infrainguinal
      bypass surgery.
AB  - BACKGROUND: The prevalence of asymptomatic carotid stenosis in patients with
      lower-extremity ischemia is unknown. This report represents the largest carotid
      screening program to date of patients undergoing leg bypass. DESIGN: Patients
      undergoing infrainguinal bypass from 1987 through 1993 on the vascular surgery
      service at Oregon Health Sciences University, Portland, underwent routine carotid
      duplex examinations to detect the presence of asymptomatic carotid stenosis.
      PATIENTS: During the study period, 352 patients underwent infrainguinal
      revascularization for ischemia, of whom 225 (64%) had no prior carotid surgery,
      carotid arteriography, or cerebrovascular symptoms. There were 117 men and 108
      women, with a mean age of 67 years. The indication for surgery was limb salvage
      in 67% and claudication in 33% of patients. RESULTS: Sixty-four patients (28.4%)
      who required lower-extremity revascularization had hemodynamically significant
      asymptomatic carotid artery stenosis or occlusion; 12.4% had stenosis of 60% or
      greater, the qualifying level for randomization in the Asymptomatic Carotid
      Atherosclerosis Study. Based on these findings, eight patients with carotid
      stenosis of 80% or greater underwent elective carotid endarterectomy. There were
      no postoperative neurologic events in the 225 leg bypass patients. By
      multivariate logistic regression analysis, the presence of carotid bruit (P <
      .001) and the presence of rest pain (P = .006) were associated with carotid
      stenosis of 50% or greater. Limiting screening to patients with carotid bruit,
      limb salvage indications for surgery, and/or advanced age excluded significant
      numbers of patients with stenosis; thus, these were not effective screening
      strategies. CONCLUSION: Screening carotid duplex scanning is indicated in
      patients who require lower-extremity revascularization.

PMID- 7632152
TI  - Familial nonmedullary thyroid cancer. An emerging entity that warrants aggressive
      treatment.
AB  - OBJECTIVE: To determine whether familial nonmedullary thyroid carcinoma behaves
      like sporadic carcinoma of follicular cell origin. DESIGN: Retrospective review.
      SETTING: University medical center. PATIENTS: Fourteen patients were treated for
      familial nonmedullary thyroid carcinoma between 1980 and 1994. Thirteen families
      were identified, with 30 affected individuals. INTERVENTIONS: Patients were
      treated with total or completion total thyroidectomy. Thirteen additional
      operations were performed to control recurrent disease. MAIN OUTCOME MEASURES:
      Stage, recurrence, and survival. Patients were followed up for a mean of 6.5
      years. RESULTS: In our 14 patients, 13 tumors were multifocal, and six of these
      were bilateral. The incidences of lymph node metastasis and local invasion were
      both 57% (n = 8). Seven patients (50%) had recurrences during follow-up.
      CONCLUSIONS: Familial nonmedullary thyroid carcinoma has a high incidence of
      multifocality and invasion and a high rate of local recurrence. Aggressive
      initial treatment and careful follow-up seem to be indicated.

PMID- 7632154
TI  - Ultrasonic resection of neuroblastomas. Long-term local tumor control.
AB  - OBJECTIVE: To evaluate the effectiveness of ultrasonic aspiration in achieving
      local tumor control of bulky neutroblastomas that are considered unresectable by
      conventional means. DESIGN: A retrospective review of 12 patients undergoing
      ultrasonic aspiration as part of multimodal treatment protocols. SETTING: A
      pediatric oncology referral center. PATIENTS: Twelve children with large
      neuroblastomas located in the abdomen (n = 5), chest (n = 5), and neck (n = 2).
      Follow-up was 1.5 to 7.5 years. INTERVENTIONS: Ultrasonic aspiration of the tumor
      was primary therapy (n = 7) or followed initial chemotherapy (n = 5). All
      patients underwent subsequent chemotherapy or autologous bone marrow
      transplantation. MAIN OUTCOME MEASURES: The incidences of residual disease and
      local recurrence were examined. RESULTS: Tumor-related symptoms were effectively
      relieved in all 12 patients. Recurrent local disease led to death in two. One
      patient died of distant metastases. CONCLUSIONS: Ultrasonic aspiration minimized
      blood loss and did not cause damage to adjacent organs. It provided nearly
      complete tumor resection, enhanced the effectiveness of chemotherapy protocols,
      and decreased the need for supportive care. Ultrasonic aspiration is a safe and
      effective method for obtaining local control of large neuroblastomas.

PMID- 7632155
TI  - Axillary lymphadenectomy for breast cancer without axillary drainage.
AB  - OBJECTIVE: To evaluate axillary lymph node dissection done without closed
      drainage in conjunction with breast conservation cancer surgery. DESIGN:
      Prospective clinical study. SETTING: Two university hospitals. PATIENTS: Eighty
      one women undergoing wide local excision of breast cancer with simultaneous or
      subsequent axillary lymph node dissection. INTERVENTIONS: No axillary drain was
      placed following axillary lymphadenectomy. MAIN OUTCOME MEASURES: The development
      and resorption of axillary seroma fluid as measured by clinical aspiration and
      serial sonographic examination. RESULTS: Thirty-four (42%) of the 81 women
      required axillary seroma aspiration even though axillary fluid was present in 92%
      (22/24) of those studied sonographically. The seromas accumulated over the first
      2 weeks following axillary dissection and resorbed over the next 2 weeks, as
      assessed by both clinical and sonographic examination. The complication rate was
      2% (2/81). The surgery was performed safely on an outpatient or short-stay basis
      in 99% (80/81) of patients. All patients except one were discharged within 23
      hours of surgery, and 56 patients were discharged directly after anesthesia.
      CONCLUSION: Axillary lymph node dissection done in conjunction with breast
      conservation surgery can be performed in an ambulatory or short-stay setting
      without axillary drainage. Postoperative seromas will resolve within 1 month, and
      fewer than half will require aspiration. Lymphadenectomy without drainage reduces
      morbidity and allows the patient greater personal comfort.

PMID- 7632156
TI  - [An experiment on drinking using breath alcohol monitor (Alcomed 3010) by an
      electrochemical method].
AB  - A drinking experiment was performed to evaluate the efficiency of a breath
      alcohol monitor, Alcomed 3010. The ethanol concentrations in blood and breath
      were determined by gas chromatography, and in particular the breath ethanol
      concentration was determined with the breath alcohol monitor and by gas
      chromatography. The results obtained by two methods were compared. Based on the
      blood and breath ethanol concentrations, the following conclusions were drawn
      reading the breath alcohol monitor. The monitor has practical merit for
      determination of the breath ethanol level. It is small, usable anywhere, with
      little error in determination. In measuring principle, tobacco and acetone did
      not affected levels with the meter, but methanol, n-propanol and n-butanol
      affected determinations with the alcohol monitor. The breath (AM)/blood (GC)
      ethanol ratio was 1:2555. Comparison of the values determined with the alcohol
      monitor and gas chromatography yielded the equation: y = 0.998 x +/- 0.012 (r =
      0.994). When determinations were made on the pure ethanol gas by the meter and
      gas chromatograph, the equation was: y = 0.974 x +/- 0.021 (r = 0.994). It may be
      said therefore that the alcohol monitor is both practically and functionally
      excellent.

PMID- 7632157
TI  - [Alcohol drinking patterns among policemen in Shiga, Kyoto, Yamaguchi and Okinawa
      prefectures].
AB  - Alcohol drinking patterns among policemen in Shiga, Kyoto, Yamaguchi and Okinawa
      prefectures were surveyed using a questionnaire on alcohol drinking during 1987
      88. The responses from 1812 (male) subjects (average age of 36) were compared to
      a similar survey in 1975-79. Drinkers accounted for 91.3% of all subjects, of
      which 6.6% drank daily, 65.6% drank more than once a week, 6.5% usually did not
      drink at all and 2.1% were abstainers. The percentage of daily drinkers decreased
      during the 10 years (13.5%) though the total number of drinkers slightly
      increased nationwide. Preferred beverages were, beer 39.9%, whisky 21.4% Japanese
      sake 17.9%, Japanese shochu 11.0%. The percentage of beer and Japanese shochu
      drinkers increased and that of Japanese sake decreased during the ten-year
      period. However, Japanese sake was the second most popular beverage in Shiga,
      Kyoto and Yamaguchi prefectures. In Okinawa, awamori (a strong kind of shochu)
      was the favorite. Especially, drinkers aged over 50 in Okinawa preferred awamori
      rather than beer. Though drinking frequency at home (banshaku) and parties
      (enkai) did not change, the consumption volume decreased during the ten-year
      period. In In particular, young drinkers drank less frequently at home. Intake
      increased with age. Our results indicate that drinking frequency and volume
      decreased during the ten-year period. In general, drinking frequency and volume
      is reported to have increased. This difference might be related to the character
      of a policeman's occupation.

PMID- 7632158
TI  - Induction mechanisms of cytochrome P450 2E1 in liver: interplay between ethanol
      treatment and starvation.
AB  - Chronic ethanol exposure causes marked induction of the ethanol-inducible
      cytochrome P450 (CYP) 2E1 isozyme in the centrilobular liver region, where
      alcoholic damage commonly is initiated. In contrast to most other CYP forms,
      which are ligand-activated at the transcriptional level, ethanol induction of
      CYP2E1 has been found to be post-translational. However, transcriptional
      activation of the CYP2E1 gene was recently described in fed animals maintained at
      very high ethanol levels. To further evaluate mechanisms of ethanol-mediated
      CYP2E1 induction we compared the effect of short-term heavy-ethanol treatment and
      fasting on CYP2E1 mRNA, protein and catalytic activity. High blood-ethanol levels
      (20-70 mM) were maintained for 3 days by regular alcohol intubations to fed or
      fasted rats. During this period, the amount of liver CYP2E1 apoprotein increased
      a maximum of 20-fold and catalytic activity 16-fold, both in fed and fasted
      animals, whereas starvation alone caused only a 4- to 5-fold increase. By
      comparison, the amount of CYP2E1 mRNA, as assayed both by Northern blot and slot
      blot, was significantly increased (5- to 6-fold) by ethanol only in fasted rats;
      this increase was smaller than that observed after fasting alone (8- to 9-fold).
      Analysis of cell lysates isolated from the periportal and perivenous region
      revealed that the increase in CYP2E1 mRNA by fasting occurred in the perivenous
      region. Thus no evidence was obtained for an increased pretranslational CYP2E1
      gene expression as a consequence of the continuous presence of ethanol at
      intoxicating levels for 3 days. CYP2E1 mRNA elevation seems to be strongly
      associated with starvation while alcohol treatment increases the amount of
      enzyme, primarily by ligand-dependent stabilization of the synthesized protein.
      Our results indicate that transcriptional activation of CYP2E1 requires the long
      term presence of highly intoxicating ethanol levels. It is conceivable that such
      activation occurs via indirect physiological responses related to those triggered
      by starvation.

PMID- 7632159
TI  - Differences in kinetic properties of pure recombinant human and mouse
      deoxycytidine kinase.
AB  - Human and mouse deoxycytidine kinase (dCK) (EC 2.7.1.74) were cloned and
      expressed in Escherichia coli. Michaelis-Menten kinetics were determined for the
      purified enzymes with 2'-deoxycytidine (dCyd), 2'-deoxyadenosine (dAdo), 2-chloro
      2'-deoxyadenosine (CdA), 2',3'-dideoxycytidine (ddCyd) and 9-beta-D
      arabinofuranosylguanine (araG) as substrates and ATP and UTP as phosphate donors.
      Both human and mouse dCK showed highest affinity to dCyd with Km values of 0.05
      0.2 microM. The anti-leukaemic compound CdA was the superior substrate of the
      nucleoside analogues tested. Both enzymes were able to efficiently utilize ATP
      and UTP as phosphate donors. However, the use of UTP instead of ATP as phosphate
      donor decreased Km values for all substrates investigated. The kinetic properties
      of mouse and human dCK differed in that the human enzyme showed higher affinity
      for the substrates dAdo, CdA, ddCyd and araG. The human enzyme also showed higher
      affinity for ATP and UTP. The ability to phosphorylate dCyd was, however, similar
      for both human and mouse dCK. At physiological concentration of the feedback
      inhibitor dCTP, mouse dCK showed lower activity than human dCK for all substrates
      investigated.

PMID- 7632160
TI  - Azelastine and flezelastine as reversing agents of multidrug resistance:
      pharmacological and molecular studies.
AB  - The effects of two new phthalazinone derivatives, azelastine (AZ) and
      flezelastine (FZ), on the reversal of resistance to doxorubicin (dox) were
      studied using two variants of the rat C6 glioblastoma cell line, selected with
      dox (C6 0.5) or with vincristine (C6 1V). Both lines presented a multidrug
      resistant phenotype which was, in the case of C6 0.5 cells, likely to be
      accompanied by an additional mechanism leading to intracellular tolerance of the
      drug. Both AZ and FZ reversed dox resistance in a concentration-dependent manner,
      and FZ was shown to be at least three times more potent than AZ. FZ was able, at
      a relatively high concentration (30 microM), to completely restore dox
      sensitivity in both cell lines. Both drugs were able to virtually restore dox
      accumulation to the level reached in sensitive cells, and, interestingly, this
      complete restoration occurred at lower concentrations of modulator than required
      for complete reversal of resistance. FZ was able to reverse dox intracellular
      tolerance of C6 0.5 cells and to restore dox accumulation at the IC50 to the
      level observed in sensitive cells. AZ and FZ both inhibited azidopine binding to
      membrane preparations of C6 0.5 and C6 1V cells, although FZ was more potent.
      Both drugs more successfully inhibited azidopine binding to membranes prepared
      from C6 1V cells (which express the mdr1b gene product) than to membranes from C6
      0.5 cells (which express the mdr1a gene product). In view of its potent activity
      on MDR, further preclinical evaluation of FZ is warranted.

PMID- 7632161
TI  - Genistein resistance in human leukaemic CCRF-CEM cells: selection of a diploid
      cell line with reduced DNA topoisomerase II beta isoform.
AB  - Genistein, an isoflavonoid derivative initially described as an in vitro protein
      tyrosine kinase inhibitor, also inhibits mammalian DNA topoisomerase II both in
      vitro and in vivo. From a human leukaemic T cell line (CCRF-CEM), two genistein
      resistant cell lines, which grow in the presence of 50 and 150 microM genistein,
      respectively, were selected and designated CEM/GN50 and CEM/GN150. Flow cytometry
      and karyotype analyses revealed that more than 95% of the parental cells were
      tetraploid whereas both resistant sublines were essentially diploid and were
      likely derived from the diploid fraction in the initial population. The CEM/GN
      cells were 3- to 4-fold resistant to genistein, and highly cross-resistant to
      certain metabolic inhibitors such as cytosine-arabinoside (50-fold) and 5-fluoro
      2'-deoxyuridine (5000-fold). This resistance was associated with a markedly
      decreased uptake of thymidine and a 10-fold reduction in thymidine kinase
      activity. The CEM/GM cells were also 15- to 30-fold cross-resistant to
      topoisomerase inhibitors (etoposide, m-AMSA, 2-Me-9-OH-ellipticinium). Comparison
      of topoisomerase II activities in the sensitive and resistant cells showed: (i)
      an approximately 2-fold reduced decatenation activity in nuclear extracts from
      the resistant cells; (ii) an approximate 30% reduction in DNA-protein cross-links
      in etoposide-treated resistant cells; and (iii) a markedly reduced expression of
      the topoisomerase II beta isoform. These data, consistent with our previous
      results, indicate that the cytotoxicity of genistein is at least in part related
      to its capacity to inhibit DNA topoisomerase II.

PMID- 7632162
TI  - Novel dithiane analogues of tiapamil with high activity to overcome multidrug
      resistance in vitro.
AB  - Dithiane analogues of tiapamil are highly active as modifiers of P-glycoprotein
      mediated multidrug resistance (MDR) in vitro. In an assay using the P
      glycoprotein over-expressing cell line KB-8-5, the most active analogues for
      decreasing vincristine resistance were the racemate Ro 11-5160 and its two
      enantiomers, Ro 44-5911 (R) and Ro 44-5912 (S). In the KB-8-5 assay, the
      resistance modification index (RMI) of Ro 11-5160 was approximately 12-fold
      higher than those of the most active reference compounds tested, dipyridamole,
      cepharanthine, reserpine and cyclosporin A, when compared at concentrations equal
      to one-tenth of the IC50 of each compound (RMI0.1). The enantiomers have similar
      resistance modifying activities, but the (S) enantiomer Ro 44-5912 is somewhat
      more active, fully reverting the vincristine sensitivity of KB-8-5 cells to the
      level of the parental KB-3-1 cells at a concentration of 2 microM. The (R)
      enantiomer attained this level of modification at a concentration of 3.5 microM.
      These concentrations are both well below their IC50 values for KB-8-5 cells (150
      microM). The enantiomers appear to interact with P-glycoprotein because they
      inhibited [3H]azidopine and [3H]-vinblastine binding to plasma membrane fractions
      prepared from resistant K562/ADR cells. However, in addition to their resistance
      modifying activities with KB-8-5 cells, these compounds also decreased the IC50
      values of vincristine and doxorubicin with KB-3-1 cells that do not express
      detectable levels of P-glycoprotein. Ro 44-5911 overcame doxorubicin and
      vincristine resistance in three colorectal cancer cell lines (DLD-1, WiDr and
      COLO 201) that express P-glycoprotein. No effect was seen with the 3 colorectal
      cell lines on the IC50 values of three drugs not related to the MDR phenotype, 5
      fluorouracil, 5'-deoxy-5-fluorouridine and cis-diaminodichloroplatinum (II). The
      in vitro vasodilatory activity of these dithianes, measured with strips of rat
      aorta contracted with KCl, was about 5% of that of verapamil. These results
      suggest that diathianes could be useful agents for MDR modification in vivo.

PMID- 7632163
TI  - Pharmacological control of human polymorphonuclear leukocyte degranulation by
      fenamates and inhibitors of receptor-mediated calcium entry and protein kinase C.
AB  - The present work was designed to study the mechanism of inhibitory action of
      flufenamic and tolfenamic acids on the degranulation response of human
      polymorphonuclear leukocytes (PMNs). We have recently shown that fenamates
      inhibit PMN degranulation as well as other PMN functions at micromolar drug
      concentrations. However, the mechanism of their action remains unknown. To
      clarify this mechanism, the degranulation response was induced by agents known to
      activate different steps in the activation cascade in PMNs: the receptor-mediated
      activator fMLP (N-formyl-L-methionyl-L-leucyl-L-phenylalanine); a calcium
      ionophore (A23187); an inhibitor of calcium-ATPase (thapsigargin); and an
      activator of protein kinase C (phorbol myristate acetate, PMA). For comparison,
      SK&F 96365 (an inhibitor of receptor-mediated calcium entry), Ro 31-8220 (an
      inhibitor of protein kinase C) and ketoprofen (another cyclooxygenase inhibitor)
      were used. Flufenamic and tolfenamic acids inhibited A23187- and fMLP-induced
      degranulation in a dose-dependent manner. The thapsigargin-triggered response was
      reduced only slightly and that induced by PMA remained unaltered. The pattern of
      the inhibitory action of fenamates differed from those of Ro 31-8220 and
      ketoprofen. The action of fenamates resembled that of the inhibitor of receptor
      mediated calcium entry, SK&F 96365, especially when A23187, fMLP or PMA were used
      to stimulate the cells. This prompted us to measure the effects of flufenamic and
      tolfenamic acids on receptor-mediated calcium entry. The two fenamates inhibited
      the fMLP-induced increase in intracellular free calcium in fura-2 loaded PMNs in
      the presence but not in the absence of extracellular calcium. The results suggest
      that the suppressive actions of fenamates on PMN degranulation are neither
      related to the activity of cyclooxygenase nor PMA-activated protein kinase C. In
      contrast, fenamates resemble the antagonist of receptor-mediated calcium entry,
      SK&F 96365, in their antagonistic action on PMN degranulation.

PMID- 7632164
TI  - Characterization of human cytochromes P450 involved in theophylline 8
      hydroxylation.
AB  - Studies were undertaken to determine which human P450 enzymes catalyze the
      metabolism of theophylline to 1,3-dimethyluric acid (1,3-DU), to facilitate
      predictions of theophylline drug-drug interactions, and to develop a noninvasive
      test for human P4501A2. Microsomes from a human cell line transfected
      individually with human P450 cDNAs for P4501A1, 1A2, 2A6, 2B6, 2C9, 2D6, 2E1, or
      3A4 were used to demonstrate that only P4501A2 exhibited catalytic activity for
      theophylline metabolism to 1,3-DU with high affinity and low capacity (Km = 0.6
      mM, Vmax = 37.8, pmol/min/mg), while P4502D6, 2E1, and 3A4 (Km = 14.4, 19.9, and
      25.1 mM, respectively, and Vmax = 219.8, 646.4, and 20.8 pmol/min/mg,
      respectively) exhibited activities with low affinity and variable capacities.
      Correlations of rates of theophylline 8-hydroxylation to 1,3-DU with other P450
      form-specific activities, in a series of ten human liver microsomal preparations,
      at 5 and 40 mM theophylline concentrations, revealed that at low concentrations
      the metabolism was catalyzed primarily by P4501A2, while at high substrate
      concentrations P4502E1 was primarily responsible for catalysis. The results with
      individually expressed P450s and hepatic microsomal preparations were consistent,
      indicating that the former system provides a qualitatively accurate reflection of
      the function of the heterogeneously expressed liver P450s. At pharmacologic
      theophylline concentrations achieved in vivo, its metabolism must thus be
      catalyzed primarily by P4501A2.

PMID- 7632165
TI  - Dissociation of the genotoxic and growth inhibitory effects of selenium.
AB  - The effects of forms of selenium compounds that enter the cellular selenium
      metabolic pathway at different points were investigated in a mouse mammary
      carcinoma cell line. The goal of these experiments was to determine if the
      genotoxicity of selenium, defined as its ability to induce DNA single-strand
      breaks, could be dissociated from activities proposed to account for its cancer
      inhibitory activity. The results demonstrated that growth inhibition, measured as
      inhibition of cell proliferation and induction of cell death, was induced by all
      the forms of selenium evaluated. However, sodium selenite and sodium selenide,
      which are metabolized predominantly to hydrogen selenide, caused the rapid
      induction of DNA single-strand breaks as an early event that preceded growth
      inhibition. Interestingly methylselenocyanate and Se-methylselenocysteine, which
      are initially metabolized predominantly to methylselenol, induced growth
      inhibition in the absence of DNA single-strand breakage. Differences in the time
      course of selenium retention, in the occurrence of membrane damage, and in the
      induction of morphological changes by selenite versus methylselenocyanate were
      noted. Collectively, these data indicate that different pathways affecting cell
      proliferation and cell death are induced depending on whether selenium undergoes
      metabolism predominantly to hydrogen selenide or to methylselenol.

PMID- 7632166
TI  - Reduction of drug ketones by dihydrodiol dehydrogenases, carbonyl reductase and
      aldehyde reductase of human liver.
AB  - In this study, we compared the enzymatic reduction of 10 drugs with a ketone
      group by homogeneous carbonyl reductase, aldehyde reductase and three dihydrodiol
      dehydrogenases of human liver cytosol. At least one and in some cases all of the
      three dihydrodiol dehydrogenases reduced each of the ten drugs. Among these
      naloxone, naltrexone, befunolol, ethacrynic acid and ketoprofen were substrates
      specific for the dehydrogenases. The other drugs--haloperidol, metyrapone,
      loxoprofen, daunorubicin and acetohexamide--were highly reduced by carbonyl
      reductase and/or aldehyde reductase. The dihydrodiol dehydrogenases also showed
      lower Km values for haloperidol and loxoprofen than did carbonyl reductase. The
      results indicate that the three dihydrodiol dehydrogenases, as well as the two
      reductases, are implicated in the reduction of ketone-containing drugs in human
      liver cytosol.

PMID- 7632167
TI  - Buthionine sulfoximine-induced glutathione depletion. Its effect on antioxidants,
      lipid peroxidation and calcium homeostasis in the lung.
AB  - The administration of buthionine sulfoximine (BSO), an irreversible inhibitor of
      gamma-glutamylcysteine synthetase, produces glutathione (GSH) depletion in
      tumors, making them sensitive to drugs and radiation. During the process, it also
      depletes GSH from normal tissues. Certain tumors require frequent doses of BSO
      for several days to produce GSH depletion. In this study, we determined that this
      chronic GSH-deficient condition lowers the antioxidant defense of the lung by
      diminishing the activities of superoxide dismutase, catalase, and glutathione
      peroxidase and the levels of ascorbic acid and alpha-tocopherol. Impaired
      antioxidant defense leads to enhanced lipid peroxidation, as indicated by
      increased levels of thiobarbituric acid reactive substances and conjugated
      dienes. The alteration of protein thiols by lipid peroxidation, is responsible
      for altered Ca2+ homeostasis, which, in turn, leads to cell injury. Cell injury
      was confirmed by elevated activities of angiotensin converting enzyme and lactate
      dehydrogenase, increased levels of protein and lactate, and histopathological
      changes.

PMID- 7632168
TI  - Inhibition of diacylglycerol kinase by the antitumor agent calphostin C. Evidence
      for similarity between the active site of diacylglycerol kinase and the
      regulatory site of protein kinase C.
AB  - Calphostin C is an anti-tumor agent that binds to the regulatory domain of
      protein kinase C and inhibits the binding of phorbol dibutyrate. Recent studies
      suggest that there may be structural similarities between protein kinase C (PKC)
      and diacylglycerol kinase (DGK). Both enzymes bind diacylglycerol and
      phosphatidylserine, and sequencing of the 80 kDa diacylglycerol kinase shows that
      it contains zinc finger-like sequences, similar to those occurring in PKC.
      Similarities in some enzymatic properties of PKC and DGK led us to examine
      whether regulatory-site inhibitors of PKC also might inhibit DGK. For these
      studies, the membrane-bound DGK was partially purified from porcine testis
      membranes. Calphostin C inhibited DGK with an IC50 in the micromolar range. The
      inhibition of DGK by calphostin C was competitive with respect to diacylglycerol
      and was not affected by the presence or absence of phosphatidylserine. Other
      inhibitors of protein kinase C were without effect, with the exception of
      Adriamycin, which inhibited at millimolar concentrations. Staurosporine, which
      binds to the catalytic domain of protein kinase C, did not inhibit DGK. The
      results suggest that there are functional similarities between the substrate
      binding site of DGK and the regulatory site of protein kinase C.

PMID- 7632169
TI  - Ozone-induced tissue injury and changes in antioxidant homeostasis in normal and
      ascorbate-deficient guinea pigs.
AB  - It has been reported previously that ozone (O3) toxicity from acute (4 hr)
      exposure is enhanced by ascorbate (AH2) deficiency in guinea pigs. We
      hypothesized that lung injury from continuous 1-week O3 exposure would also be
      increased under conditions of AH2 deficiency because of (1) a diminished
      antioxidant pool to counteract the oxidant challenge, (2) impaired reparation of
      tissue injury, and/or (3) altered antioxidant redox homeostasis. Female Hartley
      guinea pigs (260-330 g) were made AH2 deficient by providing a diet similar to
      guinea pig chow, but having no AH2. The dietary regimen was started 1 week prior
      to exposure and was continued during exposure to O3 (0, 0.2, 0.4, or 0.8 ppm, 23
      hr/day, 7 days) as well as 1 week post-exposure. Bronchoalveolar lavage (BAL) and
      tissue AH2 were measured in subgroups at the beginning of exposure (1 week on the
      AH2-deficient diet), at its termination and 1 week post-exposure. AH2 measured in
      ear tissue punches proved to be an easy and effective monitor for AH2 deficiency.
      One week on the AH2-deficient diet caused a 70-80% drop in ear, lung and liver
      AH2, while AH2 in BAL was decreased by 90%. Immediately after the exposure, total
      BAL protein and albumin (markers of lung permeability) were increased
      (approximately 50%) at 0.8 ppm with no difference between the dietary groups. O3
      caused an increase in total BAL cells and neutrophils in a concentration
      dependent manner with only a slight augmentation due to diet. Exposure to O3
      caused an increase in lung and BAL AH2 in normal guinea pigs. Glutathione and
      uric acid were also increased in the lung and BAL after O3 exposure (40-570%) in
      both dietary groups, and the levels remained elevated during the recovery period.
      Lung alpha-tocopherol was not changed due to O3. A significant overall diet
      related decrease was seen in AH2-deficient guinea pigs, immediately after the
      exposure and recovery. In summary, lung injury/inflammation following 1 week O3
      exposure and recovery were minimally affected by AH2 deficiency. Antioxidants
      also appeared to increase in response to O3 exposure despite the deficiency in
      AH2.

PMID- 7632171
TI  - The influence of brain acetaldehyde on oxidative status, dopamine metabolism and
      visual discrimination task.
AB  - The toxic effect of acetaldehyde on brain oxidative capacity and dopamine
      metabolism has been investigated in rat brains after a single intraperitoneal
      injection of acetaldehyde (5 mmol/kg) and the results compared with those from
      chronically ethanol fed rats. Acetaldehyde was present in rat brain 120 hr after
      a single dose of acetaldehyde, confirming that it is able to cross the blood
      brain barrier. Brain catalase increased significantly after acetaldehyde or
      chronic ethanol administration although there were no other significant changes
      in the total brain activity of superoxide dismutase, glutathione peroxidase or
      glutathione reductase. Dopamine turnover was increased in both experimental
      groups. The acute dose of acetaldehyde reduced the ability of the rats to relearn
      a computer visual discrimination task.

PMID- 7632170
TI  - Reduction and transport of lipoic acid by human erythrocytes.
AB  - Reduction of exogenous lipoic acid to dihydrolipoate is known to occur in several
      mammalian cells and tissues. Dihydrolipoate is a potent radical scavenger, and
      may provide significant antioxidant protection. Because lipoic acid appears in
      the bloodstream after oral administration, we have examined the reduction of
      exogenous lipoate by human erythrocytes. Normal human erythrocytes reduced
      lipoate to dihydrolipoate only in the presence of glucose; deoxyglucose did not
      substitute for glucose, indicating that the reduction of lipoate requires glucose
      metabolism. Furthermore, the reduction was shown to be NADPH dependent.
      Erythrocytes isolated from a human subject with a genetic deficiency of glucose-6
      phosphate dehydrogenase (and, therefore, deficient in the formation of NADPH) did
      not reduce lipoate. Dehydroepiandrosterone, a specific inhibitor of glucose-6
      phosphate dehydrogenase, inhibited lipoate reduction. Our findings imply that
      some of the reduction of exogenous lipoic acid is catalysed by glutathione
      reductase, a flavoprotein dehydrogenase; mitomycin C, an inhibitor of FAD
      dependent reductases, inhibited lipoate reduction by erythrocytes, and
      glutathione reductase purified from human erythrocytes was observed to reduce
      lipoic acid in a cell-free system. We further explored these findings with
      erythrocyte ghosts and liposomes. Our results indicate that a transport system
      exists for alpha-lipoic acid and dihydrolipoate; resealed erythrocyte ghosts,
      containing trapped lipoamide dehydrogenase and pyridine nucleotides, reduced
      externally added lipoate. By contrast, liposomes prepared with enzyme and
      pyridine nucleotides did not catalyze reduction of lipoate. This work indicates
      that uptake of exogenous lipoate and reduction to dihydrolipoate by normal human
      erythrocytes may contribute to oxidant protection in the human bloodstream.

PMID- 7632172
TI  - High-density lipoprotein and cerebral endothelial cells in vitro: interactions
      and transport.
AB  - Primary cultures of bovine cerebral endothelial cells were used as an in vitro
      model for the blood-brain barrier to study the transport and interactions of high
      density lipoprotein (HDL) across monolayers of these cells. Transport of 125I
      apoE free HDL across a monolayer of bovine cerebral endothelial cells occurred in
      a linear fashion up to a concentration of 70 micrograms/mL, suggesting
      paracellular transport of HDL. Bovine cerebral endothelial cells possess a high
      affinity binding site for HDL with a mean dissociation constant (KD) of 10.8 +/-
      2.6 micrograms/mL (N = 4). Maximal binding of apoE free HDL to cerebral
      endothelial cells proved to be temperature-dependent: at 4 degrees a Bmax value
      of 42 +/- 9.3 ng/mg cell protein was found, while at 37 degrees this value was
      177 +/- 70.4 ng/mg cell protein. Cell association of 125I-HDL could be
      effectively displaced by HDL, not by low-density lipoprotein or acetylated low
      density lipoprotein, and association was not coupled to degradation. The in vitro
      blood-brain barrier cell system possesses high affinity binding sites for HDL,
      which are probably not involved in the transport of HDL across cerebral
      endothelial cells.

PMID- 7632173
TI  - Enhancement by hydroxyurea of the anti-human immunodeficiency virus type 1
      potency of 2'-beta-fluoro-2',3'-dideoxyadenosine in peripheral blood mononuclear
      cells.
AB  - Ribonucleotide reductase inhibitors such as hydroxyurea (HU) and related
      compounds, at low, non-toxic doses, enhance the anti-human immunodeficiency virus
      type 1 (HIV-1) potency of both purine and pyrimidine 2',3'-dideoxynucleosides
      (ddNs) in human lymphocytes and macrophages. The most marked enhancement of
      inhibition of HIV-1 replication reported to date has been seen with the purine
      ddN 2',3'-dideoxyinosine (ddIno): a low level of HU (0.1 mM) permitted a 4.5-fold
      reduction in optimal ddIno dosage with no decrease in therapeutic effect or
      increase in toxicity. We report here even more marked enhancement by HU of the
      potency of the purine ddN 2'-beta-fluoro-2',3'-dideoxyadenosine (2'-beta-F
      ddAdo), where the addition of 0.1 mM HU permitted a 7.1-fold reduction in the
      optimal dose of 2'-beta-F-ddAdo in the phytohemagglutinin-activated peripheral
      blood mononuclear cell HIV-1 test system.

PMID- 7632174
TI  - The effect of cyclopentenyl cytosine on human SK-N-BE(2)-C neuroblastoma cells.
AB  - Human neuroblastoma SK-N-BE(2)-C cell-line cells were cultured in the presence of
      various concentrations of cyclopentenyl cytosine (CPEC). In the absence of
      cytidine, the IC50 value of CPEC for SK-N-BE(2)-C cells was 100 nM after 72 hr
      drug exposure. The IC20 value was 1 microM after 24 hr of exposure to CPEC in the
      presence of 10 microM cytidine, whereas in the absence of cytidine, CPEC at 1
      microM resulted in an IC40 value after 24 hr. Therefore, cytidine partially
      prevented the cytostatic effect of CPEC. Cells cultured with 1 microM CPEC for 72
      hr were enriched by approximately 410% with mono- and oligonucleosomes in
      comparison with cells cultured without CPEC. This enrichment was partially
      prevented with 10 microM deoxycytidine and completely prevented with 10 microM
      cytidine.

PMID- 7632175
TI  - Report on the international workshop on the use of human in vitro liver
      preparations to study drug metabolism in drug development. Held at Utrecht, The
      Netherlands, 6-8 September 1994.

PMID- 7632177
TI  - [Septic shock (I). Physiopathology, monitoring].

PMID- 7632176
TI  - Multiple biochemical blood testing as a case-finding tool in ambulatory medical
      patients.
AB  - PURPOSE: The usefulness and costs of multiple biochemical blood tests as a case
      finding tool in ambulatory medical patients are not well known. Recommendations
      are lacking or based upon results of screening asymptomatic persons. We designed
      a study to determine prospectively the yield, potential disadvantages, and
      patient charges of routine biochemical testing at our medical outpatient clinic.
      PATIENTS AND METHODS: Twenty-three biochemical parameters were evaluated in 493
      consecutive patients. Parameters not considered indicated for diagnostic or
      management purposes by the staff physicians at the first visit were classified as
      routine tests. The main outcome measures were the number and the nature of new
      diagnoses leading to a new management, the number of additional tests and visits,
      and patient charges. RESULTS: New diagnoses resulting in new management were
      found in 25 patients (5%). They were mainly lipid disorders. Seven additional
      visits and 74 further tests were caused by abnormal results of routine tests. The
      net charges for the detection of the new diagnoses leading to new management were
      $12,682. Secondary analysis revealed that the determination of only three routine
      tests (cholesterol, glucose, alanine aminotransferase) would have detected all
      clinically important diagnoses and would have reduced the charges by 30%.
      CONCLUSIONS: Routine biochemical testing is a useful case-finding tool with
      acceptable costs in middle-aged medical outpatients of a university teaching
      setting. However, the spectrum of newly detected disorders leading to changes in
      patient management is small. The results suggest that a reduced routine battery
      consisting of cholesterol, glucose, and alanine aminotransferase might be
      preferable because it will detect the clinically important diagnoses and lead to
      a substantial reduction of patient charges.

PMID- 7632178
TI  - [Candida albicans spondylodiscitis].
AB  - Infections by Candida sp. have increased notably and cause not only local but
      also systemic infections. It is rarely mentioned as an etiologic agent of
      osteomyelitis. Two cases of candidiasic spondylodiscitis are presented with the
      first being in a 33 year old intravenous drug using male who consulted for
      mechanical lumbar pain. Spondylodiscitis L2-L3 was observed upon radiological
      study. Aspiration puncture was carried out and the cultures were negative.
      Surgical biopsy was performed with spondylodiscitis and an abscess in the spine
      being observed. C. albicans was isolated in the culture. Pathological study
      confirmed the diagnosis. Cutaneous and sternocostal involvement was also
      concommitantly presented. The patient was treated with amphotericin B with a
      favorable evolution. The second case was in a 35 year old male with burns over
      65% of his body due to a laboral accident. Three months after admission the
      patient presented lumbar pain irradiating to the groin and thigh. Bone
      destruction of the second lumbar vertebra and an abscess of the right psoas were
      observed upon CT scan. Puncture biopsy was performed and C. albicans was
      isolated. Histopathologic study demonstrated osteomyelitis by Candida sp.
      Treatment with amphotericin B was started. Posteriorly urea and creatinine was
      raised. Treatment was continued with fluconazole with good therapeutic response.

PMID- 7632179
TI  - Spindling artifact of urothelial cells in post-laser treatment urinary cytology.
AB  - We reviewed 22 post-laser (Nd:YAG laser) coagulation bladder washes collected
      immediately after treatment. All washes demonstrated a striking artifact of
      cellular spindling. These spindled cells occurred singly, in loose clusters, and
      in lamellar stacks and had elongated nuclei with dense chromatin and bipolar
      cytoplasm that was fused in the stacks. Concurrent biopsies demonstrated similar
      cytologic changes. The spindling is a nonspecific epithelial response to heat.
      Conventionally electrocauterized epithelia show this artifact in biopsies, but
      since only the base of the lesion and surrounding urothelium are subjected to
      heat with electrocautery, the relatively few spindled epithelial cells created
      presumably go undetected in cytology specimens. With laser treatment, however,
      the whole urothelial surface of the lesion is coagulated, producing a much
      greater number of spindled cells. It is important to avoid misinterpreting the
      spindled cells as cells from a mesenchymal neoplasm or a sarcomatoid carcinoma,
      mistakes that were made in some of our initial cases. Malignancy cannot be
      evaluated when cells exhibit spindling artifact; this judgement should be made on
      undistorted cells. Thus, pre-laser and post-laser washes should be submitted for
      evaluation of malignancy.

PMID- 7632180
TI  - [Neoplasms associated with human immunodeficiency virus infection. Study of the
      clinical course of 70 patients].
AB  - BACKGROUND: A different epidemiologic pattern of the neoplasms associated to the
      human immunodeficiency virus (HIV) has been described in the Mediterranean area.
      The aim of the present study was to analyze the epidemiologic, clinical and
      evolutive characteristics of these patients. METHODS: A retrospective study of 74
      neoplasms in 70 patients (15% of AIDS cases) was carried out. The following
      variables were analyzed: risk group, state of the infection (HIV), stage and type
      of tumor, immunohematologic data, opportunistic infections (OI), response to
      treatment, evolution and prognostic factors. RESULTS: Thirty-four Kaposi's
      sarcomas (SK) were diagnosed, 32 non Hodgkin's lymphomas (NHL), 4 Hodgkin's
      disease (HD), 2 seminomas, 1 cutaneous carcinoma and one undifferentiated tumor.
      Sixty-eight patients were males with a mean age of 32 years. The risk group was:
      homosexual (52%), drug abuse (24%), hemophilia (14%), and heterosexual contact
      (10%). The neoplasm was the first manifestation of HIV infection in 60% of the
      patients. Sixteen patients with SK were treated with chemotherapy (CMT),
      radiotherapy (RT) or interferon and stabilization of the disease was achieved in
      50% of the cases. Twenty-six patients with NHL received treatment: 26 with CMT, 9
      with RT and 4 with surgery. Complete remission was achieved in 27% and partial in
      61% of the cases. Overall mortality was 56% and median survival 13 months. Most
      of the patients died due to progression of the tumor or infection. The prognostic
      factors associated to shortened survival were: advanced stage of AIDS, OI at the
      time of diagnosis of the tumor and a decrease in hemoglobin, total lymphocytes
      and CD4. CONCLUSIONS: The lower incidence of neoplasms among patients with
      acquired immunodeficiency disease and the differences in the distribution of the
      histologic types may be related with the demographic features of the risk groups
      in Spain. Survival is determined more by opportunistic infections than by the
      tumor itself.

PMID- 7632181
TI  - [Ethical principles of medical research].

PMID- 7632182
TI  - [Anaphylactic shock caused by food hypersensitivity: fatal outcome despite
      immediate injection of adrenaline].

PMID- 7632183
TI  - [Eosinophilic ileitis and peritonitis].

PMID- 7632184
TI  - [Adjuvant chemotherapy in gastric cancer].

PMID- 7632185
TI  - [Current treatment of bronchial asthma].

PMID- 7632186
TI  - [White or ischemic infarction: between redundancy and precision].

PMID- 7632187
TI  - [Let the threadworm live!].

PMID- 7632188
TI  - [Acute appendicitis in children].
AB  - From January 1st, 1987 to December 31st, 1989, 267 patients were operated upon
      for acute appendicitis representing 97% of emergency laparotomies at the
      Pediatric Surgery Department of Santa Maria Hospital (HSM); of these, 207 records
      were analysed using a retrospective protocol and the results were as follows:
      most frequent symptoms were abdominal pain (99% of cases) and anorexia (86%).
      Referral for surgical evaluation was made in 35.8% of cases 48 hours after the
      onset of symptoms; surgery was performed in 129 patients (62.4%) in advanced
      stages of disease, with histopathological examinations of necrotic, perforated
      and gangrenous appendices. 15 patients (7.2%) had no appendicitis-11 were found
      to have follicular hyperplasia and 4 normal histology; of these, luminal
      distention by parasitic eggs was found in 4. Antibiotic therapy was used in 89
      patients preoperatively and in 200 patients postoperatively; cefoxitin was the
      most commonly used in 89.9% and 83.0% respectively. There were 19 complications
      (9.2%): 8 parietal, 5 pelvic and 1 subphrenic abscesses, 4 total or partial
      obstructions and 1 lost drain; 4 patients (1.9%) were reoperated and there was no
      mortality.

PMID- 7632189
TI  - [Candida spondylodiscitis].

PMID- 7632190
TI  - Deafness, dysesthesia, depression, diarrhea, dropsy, and death: the case for
      sarcoidosis in Ludwig van Beethoven.

PMID- 7632191
TI  - [Dying in April?: comments on a partial reflection on the reality of Spanish
      health care].

PMID- 7632192
TI  - [The relation of biliary lithiasis to lipoproteins isolated by
      ultracentrifugation].

PMID- 7632193
TI  - [Multiple cavernous malformations of familial origin].

PMID- 7632194
TI  - Cholesterol metabolism in the RSH/Smith-Lemli-Opitz syndrome: summary of an NICHD
      conference.
AB  - During the evolution of multicellularity and attendant processes of development,
      cholesterol played a key role in the formation of the plasma membrane and outer
      mitochondrial membrane of every cell in the organism. Later functions include
      pivotal involvement in steroid, bile acid, and vitamin D metabolism and
      myelination of the nervous system. In the CNS myelination does not begin until
      the third trimester, and subcortical myelination not until after birth. The
      cholesterol of the cell membrane of the ovum is maternally derived. It is not
      known when the zygote begins making its own cholesterol during morphogenesis and
      histogenesis, but it must occur early to keep up with the dramatic rate of cell
      division in the embryo. Thus, it is a startling surprise that human embryos and
      fetuses apparently able to synthesize little cholesterol (because of a presumed
      defect of the delta 5,7-sterol, delta 7-reductase that converts 7
      dehydrocholesterol (7-DHC) into cholesterol) frequently live to term and, rarely,
      may be so mildly affected as to attend school with only mild MR. The discovery by
      G. Stephen Tint and his co-workers of the apparent 7-DHC reductase deficiency
      makes the RSH (Smith-Lemli-Opitz) syndrome the first true metabolic malformation
      syndrome. A teratological animal model which has been known for 30 years now
      appears applicable to the RSH/SLO syndrome. A multidisciplinary NICHD conference
      held on September 20-21, 1993 reviewed the numerous implications of this
      discovery and agreed unanimously that research in this field be given highest
      priority in order to better understand cholesterol synthesis in the mammalian
      brain, cholesterol transport from mother to embryo and fetus, pre- and postnatal
      metabolic compensation in structure and function for a profound block in
      cholesterol synthesis, the nature of the blood-brain barrier for cholesterol,
      treatment of affected infants, children, and adults, structure and genetic
      specification of a 7-DHC reductase enzyme (which has never been purified!) and
      its evolution, the variability of the syndrome and whether it is genetically homo
      or heterogeneous, the population genetics of the RSH syndrome, possible
      selective advantages (or disadvantages) of heterozygotes, and means of newborn
      screening, carrier detection, and prenatal diagnosis.

PMID- 7632195
TI  - Junior doctors' hours: what do they really think?
AB  - Junior doctors' hours are one of the most controversial topics under debate in
      the health service today. We undertook a detailed postal questionnaire of
      hospital doctors in training within a major teaching unit in order to assess the
      awareness and perceived implications of the incipient changes and to elucidate
      how it was felt these changes would affect both the doctors and patients. The
      questionnaire focused specifically on the effect of the changes on quality and
      continuity of patient care, junior training and socio-economic factors relating
      to the medical staff. The questionnaire was entirely anonymous and carried only
      the first author name but provision was made to determine current grade,
      specialty, age, sex and career plans of the respondents. Importantly, space was
      included at the end for pertinent comments. All junior staff in training in all
      specialties in the Cardiff area were circulated. Three hundred and twenty-six
      questionnaires were sent out and 202 were returned of which 192 were properly
      completed (59%). Almost everyone was au fait with the proposed changes. There was
      a surprisingly high level of support for changes among non-surgical trainees, and
      half felt that quality of care would improve, though the more senior the trainee,
      the less enthusiastic they were in all aspects. Many felt that far too little
      consultation with junior staff had taken place and there was generalized
      criticism of general practitioner trainees by their specializing counterparts,
      partly because of a perceived lack of commitment and partly because of blame of
      this group for the inception of the changes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7632196
TI  - Chronic penile ulceration--a further case of Crohn's disease.

PMID- 7632197
TI  - The art of being a GIA.

PMID- 7632198
TI  - Depressive personality disorder: clinical implications.
AB  - Although the concept of a depressive personality has a long and rich tradition in
      psychiatry, it has only recently been included in any official nomenclature.
      Those afflicted with depressive personality have been subsumed under a variety of
      mood disorders and other personality disorders. This article presents criteria
      for depressive personality disorder that were developed for the DSM-IV Task
      Force. A framework for validating a personality disorder, including that of
      depressive personality disorder, is presented. Results of the DSM-IV Mood
      Disorders Field Trial relevant to this issue are reported in the article. Results
      show that DSM-IV depressive personality disorder identifies a group of patients
      whose diagnosis does not overlap substantially with major depression, dysthymia,
      or early-onset dysthymia; the patients have significant social and occupational
      morbidity. These results provide significant evidence to justify the validity of
      depressive personality disorder.

PMID- 7632199
TI  - Ten years of prospective Clostridium difficile-associated disease surveillance
      and treatment at the Minneapolis VA Medical Center, 1982-1991.
AB  - OBJECTIVES: To understand the epidemiology, risks, and management of Clostridium
      difficile-associated disease (CDAD) and to establish and evaluate reliable
      methods of surveillance. DESIGN: Case finding was done by daily ward and
      laboratory rounds. The criteria for CDAD diagnosis were: at least four unformed
      stools per day for 2 days and a positive culture or cytotoxin for C difficile, or
      positive endoscopy or autopsy for pseudomembranes. SETTING: The surveillance
      covered all patients from 1982 through 1991 in the 820-bed Minneapolis Veterans
      Affairs Medical Center. PARTICIPANTS: The criteria were met by 908 patients.
      Medical service patients numbered 488; surgical patients, 420. Frequencies ranged
      from a high of 149 cases in 1982 to a low of 50 cases in 1989. RESULTS: Stool
      specimens were obtained on 898 (99%) of the 908 CDAD patients. Stools were
      culture-positive in 864 (96%) of 898, cytotoxin-positive in 569 (63%) of 898.
      Endoscopy was performed on 196 (22%) of the 908 patients, and 80 (41%) of 196
      patients had pseudomembranes. Ten (1%) of the 908 patients were diagnosed by
      endoscopy without a stool specimen, or at autopsy. No treatment was needed for
      135 (15%) of the 908 CDAD patients, and 19 (2%) of the 908 died before treatment
      was started. Oral metronidazole was the treatment for 632 (70%) of 908 patients
      (1% intolerance, 2% failure, 7% relapse) and oral vancomycin was given to 122
      (13%) of 908 patients (1% intolerance, 1% failure, 10% relapse). Twelve patients
      had pseudomembranous colitis at autopsy, and it was the primary cause of death in
      5 (0.6%) of 908. CONCLUSIONS: CDAD usually responds to oral metronidazole or
      vancomycin but is nonetheless responsible for a high morbidity and occasional
      mortality in patients even when the diagnosis and treatment are pursued
      aggressively.

PMID- 7632200
TI  - Behavior problems in 5- to 11-year-old children from low-income families.
AB  - OBJECTIVE: The aims of the present study were to survey the Child Behavior
      Checklist (CBCL) scores (behavioral section) in a nonclinical population of US
      urban children from low-income families and to compare the distribution and
      pattern of scores with the normative data in the CBCL manual (1991). METHOD: The
      sample consisted of 890 low-income children and a mother or female guardian
      selected randomly from among Seattle public school students aged 5 to 11 years.
      RESULTS: In this sample the total CBCL score as well as all subscale scores were
      significantly higher than the norms. The proportion of children who scored in the
      clinical/borderline range was also higher than the norm. CONCLUSIONS: These
      findings support previous work showing that poverty is a risk factor for mental
      distress in children. They also raise questions about the validity of the CBCL
      norms for screening or research purpose for low-income families.

PMID- 7632201
TI  - Isolated choroid plexus cysts--the need for routine offer of karyotyping.
AB  - The management of isolated fetal choroid plexus cysts remains controversial. We
      have prospectively studied 15,565 pregnancies at two large obstetric units for
      the presence of choroid plexus cysts. In all cases where cysts were present at 19
      weeks' gestation or greater, and were multiple, bilateral or solitary and greater
      than 5 mm maximum diameter, women were offered amniocentesis or placental biopsy,
      irrespective of the presence or absence of other abnormalities. Choroid plexus
      cysts were present in 152 (0.98 per cent) of cases. Four cases (2.6 per cent) of
      autosomal trisomy (three of trisomy 18, one of trisomy 21) were detected on
      prenatal karyotyping. In all cases, choroid plexus cysts were the only detectable
      prenatal anomaly. This study and a review of other large studies do not support
      the view that isolated choroid plexus cysts are a benign variant, the risk of
      trisomy being 1 in 82. Until further evidence is available, we recommend that
      cases of isolated fetal choroid plexus cysts at 19 weeks' gestation or greater
      should be offered prenatal karyotyping.

PMID- 7632202
TI  - Clinical laboratory test findings in patients with chronic fatigue syndrome.
AB  - BACKGROUND: Results of readily available clinical laboratory tests in patients
      with chronic fatigue syndrome were compared with results in healthy control
      subjects. METHODS: Cases consisted of all 579 patients who met either the Centers
      for Disease Control and Prevention, Atlanta, Ga, British, or Australian case
      definition for chronic fatigue syndrome. They were from chronic fatigue clinics
      in Boston, Mass, and Seattle, Wash. Control subjects consisted of 147 blood
      donors who denied chronic fatigue. Outcome measures were the results of 18
      clinical laboratory tests. RESULTS: Age- and sex-adjusted odds ratios of abnormal
      results, comparing cases with control subjects, were as follows: circulating
      immune complexes, 26.5 (95% confidence interval [CI] 3.4-206), atypical
      lymphocytosis, 11.4 (95% CI, 1.4-94); elevated immunoglobulin G, 8.5 (95% CI, 2.0
      37); elevated alkaline phosphatase, 4.2 (95% CI, 1.6-11); elevated total
      cholesterol, 2.1 (95% CI, 1.2-3.4); and elevated lactic dehydrogenase, 0.30 (95%
      CI, 0.16-0.56). Also, antinuclear antibodies were detected in 15% of cases vs 0%
      in the control subjects. The results of these tests were generally comparable for
      the cases from Seattle and Boston. Although these tests served to discriminate
      the population of patients from healthy control subjects, at the individual level
      they were not as useful. CONCLUSIONS: Patients with chronic fatigue syndrome who
      were located in two geographically distant areas had abnormalities in the results
      of several readily available clinical laboratory tests compared with healthy
      control subjects. The immunologic abnormalities are in accord with a growing body
      of evidence suggesting chronic, low-level activation of the immune system in
      chronic fatigue syndrome. While each of these laboratory findings supports the
      diagnosis of chronic fatigue syndrome, each lacks sufficient sensitivity to be a
      diagnostic test. Furthermore, the specificity of these findings relative to other
      organic and psychiatric conditions that can produce fatigue remains to be
      established.

PMID- 7632203
TI  - Neointimal proliferation in canine coronary arteries. A model of restenosis
      permitting local and continuous drug delivery.
AB  - BACKGROUND: A number of experimental preparations have been used to elucidate the
      pathophysiology of restenosis after percutaneous transluminal coronary
      angioplasty; however, few models have been advanced that address restenosis in
      coronary arteries, and none provides an effective means of continuous local drug
      delivery. In this report, we describe a model of restenosis in coronary arteries
      with the provision for local, continuous delivery of cytotoxic and/or anti
      proliferative agents. EXPERIMENTAL DESIGN: An ameroid constrictor was placed on
      the left circumflex coronary artery of 17 normocholesterolemic dogs. One month
      later, after substantial collateral development had ensued, a segment of the left
      circumflex coronary artery distal to the ameroid was mechanically compressed
      using surgical forceps for 10 (N = 4), 15 (N = 4), 20 (N = 2), or 30 minutes (N =
      5). In two dogs, an indwelling left circumflex catheter and implanted pump
      maintained a continuous infusion of saline at the injury site. In addition, the
      pump side port provided transcutaneous access for serial, selective coronary
      arteriography. The animals were maintained on a normal diet, without cholesterol
      or fat supplementation. RESULTS: Three weeks after vascular injury, significant
      neointimal proliferation was observed in all dogs that was morphologically
      similar to the proliferation seen after percutaneous transluminal coronary
      angioplasty in human coronary arteries. The extent of neointimal formation was
      linearly related to the duration of injury: neointimal/medial area ratios were
      0.35 +/- 0.10, 0.46 +/- 0.10, 0.58 +/- 0.03, and 1.16 +/- 0.26 (mean +/- SE)
      after 10, 15, 20, and 30 minutes of mechanical compression injury, respectively.
      CONCLUSIONS: This model produces striking neointimal proliferation in the
      coronary arteries of normocholesterolemic dogs, morphologically similar to that
      seen in human coronary restenosis specimens. The model appears suitable to test
      the efficacy of agents with the potential to inhibit neointimal formation,
      providing continuous intracoronary drug delivery, as well as transcutaneous
      access for serial, selective arteriography.

PMID- 7632204
TI  - Setting priorities for children's health: viewpoints of family physicians and
      pediatricians.
AB  - BACKGROUND: In this study family physicians and pediatricians were asked to rank
      public health goals for children for the year 2000 and to assign responsibility
      for implementing these goals. METHODS: All members of the New Jersey chapters of
      the American Academy of Pediatrics and the American Academy of Family Physicians
      were sent a one-time mail questionnaire. Statistical analysis of responses, a
      review of written comments, and follow-up telephone interviews completed the
      study. RESULTS: About 500 physicians returned the surveys (25 percent response
      rate). The highest ranked public health goals were reducing tobacco, alcohol, and
      other drug abuse; improving physical activity and fitness; immunizing against and
      controlling infectious diseases; and improving maternal and infant health.
      Physicians assigned prevention efforts to the federal government, the family, and
      the individual. CONCLUSIONS: Family physicians and pediatricians routinely
      interact with two of the parties to whom they assign prevention responsibility-
      the individual and the family. The ability of physicians to influence these
      parties will increase if universal access to primary care and preventive services
      becomes law. This means they will also be in a unique position to influence high
      priority public health goals for children.

PMID- 7632205
TI  - Alveolar-arterial oxygen gradient in the assessment of acute pulmonary embolism.
AB  - PURPOSE: The purpose of this investigation is to evaluate the utility of the
      alveolar-arterial (A-a) oxygen gradient in the diagnosis of acute pulmonary
      embolism (PE) among patients who participated in the Prospective Investigation of
      Pulmonary Embolism Diagnosis (PIO-PED). METHODS: Pulmonary embolism was diagnosed
      (n = 280) or excluded (n = 499) by angiography in all patients. Patients were
      then categorized as (1) the entire cohort, (2) no prior cardiopulmonary disease
      and no prior PE, and (3) no prior PE or deep venous thrombosis. Normal values of
      the A-a gradient were defined in three ways: (1) values < or = 20 mm Hg; (2)
      values < or = age/4 + 4; and (3) values based on age from the literature.
      RESULTS: When a normal A-a gradient was defined as < or = 20 mmHg, 11 to 14% of
      patients with PE in the three categories of patients had a normal A-a gradient.
      When the equation age/4 + 4 was used, 8% to 10% of patients with PE in the three
      categories of patients had a normal A-a gradient. With age-related values from
      the literature, 20 to 23% of patients with PE in the three categories of patients
      had a normal A-a gradient. The A-a gradient was normal in comparable percentages
      of patients who did not have PE. CONCLUSION: Normal values of the A-a gradient
      did not exclude the diagnosis of acute PE.

PMID- 7632206
TI  - Has HRT come of age?

PMID- 7632207
TI  - Ondansetron for prevention of postoperative nausea and vomiting following minor
      oral surgery: a double-blind randomized study.
AB  - The efficacy and safety of ondansetron in preventing postoperative nausea and
      vomiting following minor oral surgery was evaluated in a prospective randomized
      double-blind study. Of a total of seventy-seven patients, randomly 38 had 4 mg of
      ondansetron and 39 had normal saline as placebo intravenously immediately prior
      to induction of anaesthesia. A standard general anaesthetic with thiopentone,
      suxamethonium, fentanyl, nitrous oxide and isoflurane was employed.
      Postoperatively nausea was assessed verbally and on a visual analog scale at 1, 4
      and 24 hours from the time of awakening. Episodes of vomiting were recorded.
      Eight patients (21.1%) in the ondansetron group compared to 19 (48.7%) in the
      placebo group had nausea (P < 0.05) and 1 (2.6%) in the ondansetron group
      compared with 9 (23.1%) in the placebo group vomited (P < 0.05). Patients who
      vomited twice or more and the number who required a rescue antiemetic were
      significantly fewer in the ondansetron group (P < 0.05). Cardiovascular
      parameters were stable and showed no significant difference in the two groups.
      There were no significant adverse effects that could be directly attributable to
      ondansetron.

PMID- 7632208
TI  - Physician-assisted death.
AB  - Physician-assisted death includes both euthanasia and assistance in suicide. The
      CMA urges its members to adhere to the principles of palliative care. It does not
      support euthanasia and assisted suicide. The following policy summary includes
      definitions of euthanasia and assisted suicide, background information, basic
      ethical principles and physician concerns about legalization of physician
      assisted death.

PMID- 7632209
TI  - Abortion: one Romania is enough.

PMID- 7632210
TI  - Cord-blood-cell transplantation--a real sleeper?

PMID- 7632211
TI  - Abuse and neglect of elderly persons.

PMID- 7632212
TI  - Changes in energy expenditure resulting from altered body weight.
AB  - BACKGROUND: No current treatment for obesity reliably sustains weight loss,
      perhaps because compensatory metabolic processes resist the maintenance of the
      altered body weight. We examined the effects of experimental perturbations of
      body weight on energy expenditure to determine whether they lead to metabolic
      changes and whether obese subjects and those who have never been obese respond
      similarly. METHODS: We repeatedly measured 24-hour total energy expenditure,
      resting and nonresting energy expenditure, and the thermic effect of feeding in
      18 obese subjects and 23 subjects who had never been obese. The subjects were
      studied at their usual body weight and after losing 10 to 20 percent of their
      body weight by underfeeding or gaining 10 percent by overfeeding. RESULTS:
      Maintenance of a body weight at a level 10 percent or more below the initial
      weight was associated with a mean (+/- SD) reduction in total energy expenditure
      of 6 +/- 3 kcal per kilogram of fat-free mass per day in the subjects who had
      never been obese (P < 0.001) and 8 +/- 5 kcal per kilogram per day in the obese
      subjects (P < 0.001). Resting energy expenditure and nonresting energy
      expenditure each decreased 3 to 4 kcal per kilogram of fat-free mass per day in
      both groups of subjects. Maintenance of body weight at a level 10 percent above
      the usual weight was associated with an increase in total energy expenditure of 9
      +/- 7 kcal per kilogram of fat-free mass per day in the subjects who had never
      been obese (P < 0.001) and 8 +/- 4 kcal per kilogram per day in the obese
      subjects (P < 0.001). The thermic effect of feeding and nonresting energy
      expenditure increased by approximately 1 to 2 and 8 to 9 kcal per kilogram of fat
      free mass per day, respectively, after weight gain. These changes in energy
      expenditure were not related to the degree of adiposity or the sex of the
      subjects. CONCLUSIONS: Maintenance of a reduced or elevated body weight is
      associated with compensatory changes in energy expenditure, which oppose the
      maintenance of a body weight that is different from the usual weight. These
      compensatory changes may account for the poor long-term efficacy of treatments
      for obesity.

PMID- 7632213
TI  - Family practice maternity care in America: ruminations on reproducing an
      endangered species--family physicians who deliver babies.
AB  - BACKGROUND: The majority of family physicians do not deliver babies. One reason
      might be the family physician's intrinsic comfort with person- or patient
      centered care compared with the common obstetric approach of disease or physician
      centered maternity care. Another reason might be the uncritical intrusion of
      technology into maternity care. In addition, family physicians often are made to
      feel unwelcome in many maternity care systems. METHODS: The medical literature
      from 1984 to 1994 was searched for the topics of obstetrics, maternity care,
      family-centered birthing, and family practice education. Reasons to argue whether
      family physicians should provide maternity care were selected, and articles were
      chosen that described the self-reported reasons students, residents, or
      physicians give whether to provide maternity care. RESULTS AND CONCLUSIONS: There
      is no scientifically supportable reason for excluding family physicians from
      maternity care in any setting, and the current maternity care system, in many
      locations, creates an attitude of taught helplessness among family physicians. In
      addition, family practice educators must for a variety of reasons be the primary
      role models and teachers of family-centered birthing for family practice
      learners. Generally, the groups that should be involved in providing maternity
      care in the future should include (1) better informed and more independent
      pregnant patients, (2) maternity care nurses, (3) doulas, (4) midwives, (5)
      family physicians, and (6) specialized physicians. Specifically, family
      physicians and midwives have a historic and philosophic similarity that would
      argue for a much closer working and practicing relationship between these two
      professionals. Family-centered birthing provides excellent outcomes. Birthing is
      both foundational and intrinsic to family practice. Conversely, without family
      physicians maternity care in America might not be able to reach its full
      potential.

PMID- 7632214
TI  - To be or not to be? Nurse? Researcher? Or both?

PMID- 7632215
TI  - Prison policies put inmates at risk.

PMID- 7632216
TI  - Why do so few patients appeal against detention under Section 2 of the Mental
      Health Act?
AB  - OBJECTIVE: To determine why most patients do not exercise their right of appeal
      against detention under section 2 of the Mental Health Act 1983. DESIGN: Part one
      -retrospective analysis of the clinical notes of patients detained under section
      2 of the Mental Health Act. Part two-interviews with patients on the penultimate
      day before the deadline for lodging an appeal. SETTING: In part one, five
      districts in the Oxfordshire Regional Health Authority. In part two, six
      hospitals from three districts in the region. SUBJECTS: In part one all patients
      detained under section 2 in the five districts in 1993 (n = 418). In part two
      interviews with 40 patients detained under section 2 in the six hospitals.
      RESULTS: Patients were more likely to appeal if they were educated to A level
      standard (odds = 2.26; P = 0.0014) or had had a previous admission (2.19, P =
      0.0029). Patients with a diagnosis of depression (0.31; P = 0.0.15) or dementia
      (0.0003, P = 0.0001) were less likely to appeal. Compared with those who appealed
      (n = 12) those who did not (n = 28) showed less understanding of their rights (P
      = 0.034) and poorer comprehension of sentences from the booklet describing
      patients' rights (P = 0.057). The main reasons given for not appealing were not
      being aware of the appeals process and being deterred by having to appeal in
      writing. After they received a full explanation of their rights 12 of those who
      did not appeal said that they wished to appeal and four did so within the time
      remaining before the deadline. Of 40 patients, 39 said there should be an
      automatic right of appeal. CONCLUSIONS: The appeals procedure against detention
      under section 2 of the Mental Health Act is not a satisfactory way of protecting
      the civil liberties of patients. If patients were fully informed of their rights
      they would probably be much more likely to appeal.

PMID- 7632217
TI  - A second locus for Marfan syndrome maps to chromosome 3p24.2-p25.
AB  - Marfan syndrome (MFS) is an autosomal dominant connective-tissue disorder
      characterized by skeletal, ocular and cardiovascular defects of highly variable
      expressivity. The diagnosis relies solely on clinical criteria requiring
      anomalies in at least two systems. By excluding the chromosome 15 disease locus,
      fibrillin 1 (FBN1), in a large French family with typical cardiovascular and
      skeletal anomalies, we raised the issue of genetic heterogeneity in MFS and the
      implication of a second locus (MFS2). Linkage analyses, performed in this family,
      have localized MFS2 to a region of 9 centiMorgans between D3S1293 and D3S1283, at
      3p24.2-p25. In this region, the highest lod score was found with D3S2336, of 4.89
      (theta = 0.05). By LINKMAP analyses, the most probable position for the second
      locus in MFS was at D3S2335.

PMID- 7632218
TI  - Fatal intracranial haematomas in two patients with Brown snake envenomation.

PMID- 7632219
TI  - Risk factors for breast cancer.

PMID- 7632220
TI  - De la Chapelle dysplasia (atelosteogenesis type II): case report and review of
      the literature [corrected].
AB  - We report a male infant with de la Chapelle dysplasia (atelosteogenesis type II),
      a skeletal dysplasia characterized by severe shortening of the long bones,
      deficient ossification of distinct parts of the skeleton, cleft palate and
      neonatal death from asphyxia. This is a rare condition with only 10 patients
      described in the literature. We report the clinical, radiographical and
      histopathological data and summarize the data on the total of 11 patients.
      Differential diagnosis with diastrophic dysplasia and atelosteogenesis (type I)
      is discussed. On clinical and histological grounds we hypothesize that de la
      Chapelle dysplasia and diastrophic dysplasia are closely related. The mode of
      inheritance is autosomal recessive.

PMID- 7632221
TI  - Health is a fundamental right.

PMID- 7632222
TI  - Same bed, different dreams.

PMID- 7632223
TI  - Arabians bring Roses to Egypt.

PMID- 7632224
TI  - Increased consumption of polyunsaturated oils may be a cause of increased
      prevalence of childhood asthma.

PMID- 7632226
TI  - Regarding judging and abstract selection guidelines.

PMID- 7632225
TI  - Prenatal diagnosis of the two-vessel cord: implications for patient counselling
      and obstetric management.
AB  - The study was designed to investigate the implications of the sonographic
      diagnosis of the two-vessel umbilical cord for patient counselling and pregnancy
      management. Retrospective analysis was carried out of prenatal findings and
      pregnancy outcomes when a two-vessel cord was diagnosed in utero. Eighty-two
      fetuses each with a single umbilical artery were diagnosed by ultrasound. Ten
      were aneuploid, including nine with visible structural defects and one with early
      onset intrauterine growth retardation. Of the remaining 72, 31 had other
      anomalies diagnosed postnatally; 27 of these had structural defects detected on
      ultrasound examination. However, in nine of these 27 sonographically abnormal
      fetuses, one or more major structural defects were missed by ultrasound
      examination. Among the 45 chromosomally normal fetuses with no visible defects on
      scan, four had anomalies diagnosed after birth. Among the chromosomally normal
      singletons, six of 22 with other anomalies seen on scan and seven of 38 with no
      other visible defects on scan had intrauterine growth retardation. Among
      chromosomally normal twins, one of two with other anomalies seen and two of five
      appearing otherwise normal had intrauterine growth retardation; one twin set was
      delivered at 23 weeks after the demise of both twins. Karyotyping is recommended
      whenever a two-vessel cord is seen in association with symmetric intrauterine
      growth retardation or any other defect. The fetus diagnosed with a two-vessel
      cord and any other anomaly by ultrasound often has additional structural defects
      not seen on scan. The fetus with an isolated two-vessel cord on scan seldom has
      unrecognized major anomalies, but is at risk for intrauterine growth retardation.

PMID- 7632227
TI  - Mismatch repair deficiency in phenotypically normal human cells.
AB  - Tumor cells in patients with hereditary nonpolyposis colorectal cancer (HNPCC)
      are characterized by a genetic hypermutability caused by defects in DNA mismatch
      repair. A subset of HNPCC patients was found to have widespread mutations not
      only in their tumors, but also in their non-neoplastic cells. Although these
      patients had numerous mutations in all tissues examined, they had very few
      tumors. The hypermutability was associated with a profound defect in mismatch
      repair at the biochemical level. These results have implications for the relation
      between mutagenesis and carcinogenesis, and they suggest that mismatch repair
      deficiency is compatible with normal human development.

PMID- 7632228
TI  - Detection of excretory-secretory circulating antigens in sheep infected with
      Fasciola hepatica and with Schistosoma mansoni and F. hepatica.
AB  - Two groups of sheep were exposed to Fasciola hepatica and Schistosoma mansoni/F.
      hepatica infections, respectively, to determine the time of appearance of F.
      hepatica circulating excretory-secretory (FhES) antigens. Five sheep were
      infected orally with 400 F. hepatica metacercariae. Five additional sheep were
      infected first percutaneously with 5000 S. mansoni cercariae, and 10 weeks later
      orally with 400 F. hepatica metacercariae. Antigen detection was performed in the
      two groups by a double antibody microELISA. In the group infected with F.
      hepatica, circulating FhES antigens were detected in all five animals. In the
      group infected first with S. mansoni none of the sera had positive optical
      density values for FhES antigens throughout the 10 week period following
      infection. After F. hepatica challenge, FhES antigens were detected in all
      animals. Thus, sheep infected with S. mansoni did not develop detectable F.
      hepatica circulating antigens during the 10 week period following Schistosoma
      infection. Anti-FhES antibodies were detected by FAST-ELISA, and all animals
      infected with F. hepatica were positive. In the group infected with S. mansoni,
      cross-reactive antibodies to F. hepatica were detected by 4-6 weeks post
      infection. All sheep with double infections showed high antibody levels by 2
      weeks after infection with F. hepatica.

PMID- 7632229
TI  - [Euthanasia].

PMID- 7632230
TI  - Indigestion of late pregnancy in a cow.

PMID- 7632231
TI  - Problem-based learning: is it worth it?

PMID- 7632232
TI  - [Aspirin yes, but how much?].

PMID- 7632233
TI  - [The risks of delay in steroid therapy for confirming by biopsy a clinical
      diagnosis of temporal arteritis. A case of sudden blindness].

PMID- 7632234
TI  - Assessment for medical clearance.

PMID- 7632235
TI  - TMD series.

PMID- 7632236
TI  - Rethinking sexual health clinics. Trainees need integrated training programme.

PMID- 7632237
TI  - Why do so few patients appeal against detention under section 2 of the Mental
      Health Act? Intellectually elite are more likely to appeal.

PMID- 7632238
TI  - Preventing crime and violence. A population approach is needed.

PMID- 7632239
TI  - Interpreting hospital death rates.

PMID- 7632240
TI  - HIV infection in prisons. What about the WHO guidelines?

PMID- 7632241
TI  - Management of ventricular fibrillation by doctors in cardiac arrest teams. Local
      training also has major impact.

PMID- 7632242
TI  - Problem solving treatment for major depression in primary care. There is a place
      for a combined treatment approach.

PMID- 7632243
TI  - Number needed to treat. Risk measures expressed as frequencies may have a more
      rational response.

PMID- 7632244
TI  - Animal health care in Egypt.

PMID- 7632245
TI  - Guaranteed safe meat?

PMID- 7632246
TI  - Microbiologic evaluation of carcasses before and after washing in a beef
      slaughter plant.
AB  - The effect of washing on the bacterial contamination of beef carcasses in a
      modern abattoir was evaluated. Twenty-six carcasses were evaluated at the end of
      the slaughter process before and after washing, and 13 other carcasses were
      evaluated only after being washed. An excision sample (5 x 5 x 0.5 cm) was
      collected from 10 sites on each carcass immediately before washing and at an
      adjacent site immediately after washing. Aerobic bacterial colonies were
      enumerated, using hydrophobic grid membrane filter technology. After washing, the
      log10 of the most probable number of growth units/cm2 decreased (P < 0.01) at the
      lateral rump site, increased (P < 0.01) at the thorax and neck sites, but was
      unchanged at the other 7 sites, compared with before washing. The sample size
      required to estimate, within 0.5 log10 units, the mean log10 most probable number
      of growth units/cm2 at a site for use in future group-carcass evaluations was
      determined and compared with a previously used sample size definition. It was
      concluded that the washing process described did not result in a major change in
      the bacterial contamination of carcasses.

PMID- 7632247
TI  - Bull selection methods.

PMID- 7632248
TI  - Autopsy and medical education.

PMID- 7632249
TI  - Nutrition and hydration for the terminally ill.

PMID- 7632250
TI  - Translocation (8;21) in acute myeloid leukemia: when to treat? That is the
      question!!

PMID- 7632251
TI  - Anaemia in lambs.

PMID- 7632252
TI  - Otitis media.

PMID- 7632253
TI  - Continuous use of neuromuscular relaxants in the management of head injured
      patients.

PMID- 7632254
TI  - Aid to diagnosis of melanoma in primary medical care. Doubling of excisions of
      genuine disease is the important issue.

PMID- 7632255
TI  - GPs' attitudes to a self diagnosis of myalgic encephalomyelitis. Sufferers
      continue to be misrepresented.

PMID- 7632256
TI  - Medical profession in US speaks out over abortion.

PMID- 7632257
TI  - Success of NHS and Community Care Act 1990 for elderly people.

PMID- 7632258
TI  - Is laparoscopic cholecystectomy without intraoperative cholangiography a safe
      operation?

PMID- 7632259
TI  - Residency choice blocked for IMG.

PMID- 7632260
TI  - TNF and pneumonia.

PMID- 7632261
TI  - Increased frequency of obstructive airway abnormalities with long-term
      tracheostomy.

PMID- 7632262
TI  - Staging bronchoscopy in the preoperative assessment of a solitary nodule.

PMID- 7632263
TI  - Late maternal mortality due to paroxysmal nocturnal hemoglobinuria and pregnancy.

PMID- 7632264
TI  - Food safety considerations.

PMID- 7632265
TI  - Possible mechanism of bacterial invasion based on the concept of percolation in
      porous media (in this particular case, periodontal tissues)

PMID- 7632266
TI  - Mandatory reporting of loss of consciousness or confusion due to alcohol.

PMID- 7632267
TI  - The clinical benefit of the bicaval technique for cardiac transplantation.

PMID- 7632268
TI  - Sweet's syndrome.

PMID- 7632269
TI  - Lost opportunity cost of surrogate markers in post-transfusion hepatitis.

PMID- 7632270
TI  - Tuberculosis in Australia.

PMID- 7632271
TI  - Intramuscular injections and vaccine-associated poliomyelitis.

PMID- 7632272
TI  - Transplantation of cord-blood cells.

PMID- 7632273
TI  - Case 5-1995: arteritis with multiple cerebral infarcts.

PMID- 7632275
TI  - Other people's money.

PMID- 7632274
TI  - Povidone-iodine to prevent ophthalmia neonatorum.

PMID- 7632276
TI  - UW Medical School faculty are dedicated to patients' needs.

PMID- 7632277
TI  - Multiple biochemical blood testing.

PMID- 7632278
TI  - Prenatal diagnosis of SLO syndrome.

PMID- 7632279
TI  - First trimester versus term trophoblast cultures: can we learn about implantation
      from both?

PMID- 7632280
TI  - Fetal gender and fetal growth retardation: fact or artifact?

PMID- 7632281
TI  - Depth of the rabbit epidural space.

PMID- 7632282
TI  - Clarithromycin therapy for Mycobacterium avium complex bacteremia.

PMID- 7632283
TI  - The distinction between active and passive euthanasia.

PMID- 7632284
TI  - Arranging emergency hospital admission.

PMID- 7632285
TI  - Vitamin A derivatives and HPV balanitis.

PMID- 7632286
TI  - Renal transplantation--a fundamental right?

PMID- 7632287
TI  - Elaborate decision criteria for media fill tests.

PMID- 7632288
TI  - Measuring continuous Fick cardiac output.

PMID- 7632289
TI  - Nicotine skin patch treatment and adverse reactions: skin irritation, skin
      sensitization, and nicotine as a hapten.

PMID- 7632290
TI  - The tilt test: effect of diabetes mellitus and antihypertensive medication on
      normal values.

PMID- 7632291
TI  - Seasonal rupture of aneurysms.

PMID- 7632292
TI  - Binge drinking in college.

PMID- 7632293
TI  - Neuropsychological effects of exposure to sheep dip.

PMID- 7632294
TI  - Thrombocytopenia reported in association with hepatitis B and A vaccines.

PMID- 7632295
TI  - Helicobacter pylori eradication and reinfection.

PMID- 7632296
TI  - Cabergoline in Parkinson's disease.

PMID- 7632297
TI  - Hard-palate mucosa graft in Stevens-Johnson syndrome.

PMID- 7632298
TI  - Oral imipramine and acute angle-closure glaucoma.

PMID- 7632299
TI  - Arthroscopic assessment of Kienbock's disease.
AB  - Arthroscopic examination was performed on 32 wrists of 32 patients with
      Kienbock's disease to relate the appearance of the intraarticular structures,
      particularly the articular cartilage, to the radiographic stage. The articular
      cartilage showed osteoarthritic changes in stage III, although this was not
      evident on plain radiographs. Cracking in the distal facet and flapping at the
      proximal facet of the lunate were identified as features of Kienbock's disease.
      The incidence of interosseous ligament tears was correlated with radiographically
      determined stage, whereas changes in triangular fibrocartilage were correlated
      with age and ulnar variance. Wrist arthroscopy is a useful staging tool for
      Kienbock's disease, supplying helpful information about the intraarticular
      pathoanatomy which can be used to guide patient management.

PMID- 7632300
TI  - Influence of various irrigation fluids on articular cartilage.
AB  - When bovine articular cartilage was incubated in Ringer's solution, considerable
      amounts of proteoglycan were washed out of the cartilage. Thus, 4% of the
      proteoglycan was lost into the medium during an incubation of 4 hours.
      Subsequently, it was found that ionic aqueous media like saline or Ringer's
      solution extracted much more proteoglycan than ion-free media like distilled
      water or a variety of carbohydrate containing solutions. In separate experiments,
      it could be shown that solutions of 20% sorbitol and 2% mannitol exhibited
      particularly low proteoglycan extracting properties. It was found that the
      extraction of proteoglycan was dependent on the ion concentration in the aqueous
      media. The extraction of proteoglycan by sodium chloride was negligible at NaCl
      concentrations of 0.1% and lower. Proteoglycan loss from cartilage was only
      induced at 0.9% NaCl. Using intact rat femoral heads it could be shown that the
      elution of proteoglycan from cartilage occurred as well when the cartilage was
      intact. Here, the elution occurred at a slower rate but the differences between
      ionic and ion-free solutions were greater. By electronmicroscopic examination of
      bovine cartilage incubated in different media, it was observed that Ringer's
      solution induced a more uneven and rougher appearance of the cartilage surface
      than did 10% mannitol solution, indicating that probably a denudation of collagen
      fibers occurs on the loss of proteoglycan from the cartilage. Because the
      observed proteoglycan washout occurred within rather short periods of contact of
      the cartilage with the medium, it is concluded that this may be of relevance for
      the clinical situation during arthroscopic procedures. The use of preferably
      isotonic carbohydrate solutions like 5% mannitol is suggested to prevent
      unnecessary loss of proteoglycan from hyaline cartilage.

PMID- 7632301
TI  - The popliteus as a retractor of the lateral meniscus of the knee.
AB  - Because of inconsistencies in the literature regarding popliteus and its relation
      to the lateral meniscus, it was decided to investigate the influence on the
      behavior of the lateral meniscus of contraction of the popliteus muscle via
      arthroscopy. A series of 50 knees from 44 patients who underwent elective
      arthroscopic surgery were examined. During arthroscopy, popliteus was stimulated
      to contract using surface electrodes. Any resultant meniscal retraction was
      observed and recorded. Thirty-one knees showed such retraction, and no retraction
      was observed in the remaining 19 knees. The clinical implications of this study
      are limited, but the results may support a number of proposed theories. It may be
      concluded that in a population exhibiting normal, intact lateral menisci,
      popliteus variably acts as a retractor of the lateral meniscus.

PMID- 7632302
TI  - Definitive landmarks for reproducible tibial tunnel placement in anterior
      cruciate ligament reconstruction.
AB  - The purpose of this prospective study was to define constant anatomic
      intraarticular and extraarticular landmarks that can be used as definitive
      reference points to reproducibly create a tibial tunnel for anterior cruciate
      ligament (ACL) reconstruction that (1) results in an impingement-free graft in
      full extension without an intercondylar roofplasty; (2) positions the tibial
      tunnel's intraarticular orafice sagittally central in the original ACL insertion
      without visually guessing; (3) positions the tibial tunnel such that the sagittal
      tunnel-plateau angle is parallel with the sagittal intercondylar roof-plateau
      angle in full extension to minimize shear seen by the graft at the tibial tunnel
      inlet, and by doing so; (4) maximizes tunnel length to avoid patellar tendon
      graft-tunnel length mismatch allowing for endosteal interference screw fixation
      on both sides of the joint. Anatomic dissections in 50 knees showed the ACL
      sagittal central insertion point on the intercondylar floor averages 7 mm (range
      7 to 8 mm) sagittally anterior to the anterior margin of the posterior cruciate
      ligament (PCL) with the knee flexed 90 degrees such that the PCL may be used as a
      reliable reference landmark for locating the ACL sagittal central insertion. This
      constant relationship was found to be independent of knee size. Extraarticularly,
      beginning the tibial tunnel sagittally 1 cm above the superior (sartorial) border
      of the pes anserinus insertion and coronally 1.5 cm posteromedial from the medial
      margin of the tibial tubercle along the superior surface of the pes, directed
      toward the sagittal central ACL insertion, led to a sagittal tunnel-plateau angle
      that averaged 68 degrees (range 64 degrees to 72 degrees) with a corresponding
      tunnel length that averaged 58 mm (range 50 to 65 mm) in 23 knees. This data
      correlated well with data obtained clinically in a series of 50 consecutive ACL
      reconstructions using intraarticular PCL and extraarticular pes anserine-medial
      tibial tubercle referenced tibial tunnels in which postoperative full extension
      lateral radiographs confirmed a sagittal tunnel-plateau angle parallel or near
      parallel with the intercondylar roof-plateau angle in all cases averaging 68
      degrees +/- 3.8 degrees. Tibial tunnel length averaged 60 mm (range 52 to 66 mm)
      and in no case was there a patellar tendon autograft-tunnel length mismatch.

PMID- 7632303
TI  - Tibial interference screw removal following anterior cruciate ligament
      reconstruction.
AB  - A small number of patients developed pain and tenderness at the tibial tunnel
      following anterior cruciate ligament reconstruction. Twenty-three knees in 22
      patients underwent removal of the tibial interference screw. Ten knees had a
      preoperative flexion contracture and underwent a concomitant procedure to address
      the loss of motion at the time of hardware removal. In the 13 knees with full
      extension, the interval between ligament reconstruction and screw removal
      averaged 16 months. Eleven of these knees also underwent arthroscopy, but no
      intra-articular causes of pain were identified. Roentgenographic analysis showed
      protrusion of the interference screw above the tibial cortex in three cases.
      Follow-up after hardware removal averaged 2 years. Tibial tunnel tenderness
      resolved in 21 of 23 knees, including those of the two patients who underwent
      hardware removal alone. Although it cannot be stated with certainty that tibial
      interferences screws may cause pain, this review suggests an association. This is
      an uncommon problem and it is estimated to be a factor in less than 3% of the
      author's anterior cruciate ligament reconstructions. More common causes of knee
      pain should be sought before electing to remove the tibial interference screw.

PMID- 7632304
TI  - Tibial chondral fissures associated with the lateral meniscus.
AB  - This article describes a relatively common lesion of the lateral tibial plateau
      that has not been reported in the literature. This lesion is a fissure of the
      articular cartilage parallel to the lateral meniscal rim. Sometimes asymptomatic,
      this articular fissure was noted in 10 of 61 consecutive patients (16%)
      undergoing knee arthroscopy in an outpatient surgery unit. This chondral fissure
      often demarcates an abrupt transition between firm and healthy articular
      cartilage, which is covered by the lateral meniscus, and exposed articular
      cartilage, which is soft and fibrillated. Progressive articular degeneration of
      knees with this lesion has not been documented; therefore, the clinical
      significance of these chondral fissure is not yet known.

PMID- 7632305
TI  - Specificity and sensitivity of the anterior slide test in throwing athletes with
      superior glenoid labral tears.
AB  - This study documents the sensitivity and specificity of a clinical test to aid in
      the diagnosis of superior glenoid labral lesions. The anterior slide test, a
      method of applying an anteriorly and superiorly directed force to the
      glenohumeral joint, was performed on several groups of athletes. These included
      symptomatic athletes with isolated superior labral tears, rotator cuff tears, and
      instabilities, and asymptomatic athletes with rotational deficits. In addition,
      non-throwing athletes were tested. The sensitivity of the test was 78.4%, and the
      specificity was 91.5%. This study shows that the anterior slide test can be used
      in the clinical examination, in that it has high specificity for superior labral
      lesions, but not enough sensitivity to be the sole diagnostic criterion for these
      lesions.

PMID- 7632306
TI  - Arthroscopic subacromial decompression: two- to seven-year follow-up.
AB  - Arthroscopic subacromial decompression (ASD) was performed in 88 patients (90
      shoulders) with stage II or early III impingement syndrome of the shoulder
      unresponsive to nonoperative treatment. The purpose of this retrospective study
      was to evaluate the follow-up an average of 41 months (range 24 to 82 months)
      after surgery. We wished to compare results in (1) patients with and without
      rotator cuff tears, (2) in athletes and nonathletes, and (3) in throwers and
      nonthrowers. Patients were evaluated by (1) Neer's Criteria for Satisfactory
      Result, (2) the UCLA Shoulder RAting Scale, (3) the Shoulder and Elbow Surgeons
      Rating Scale, (4) a detailed questionnaire, and (5) patient satisfaction. In the
      follow-up group (n = 90), 80% met Neer's criteria for satisfactory result; 94%
      had satisfactory results by the UCLA Shoulder Scale; 95% had a satisfactory
      result by the Shoulder and Elbow Society Scale; and 93% of shoulder patients
      expressed satisfaction at follow-up. There were no statistically significant
      differences in function between the group without rotator cuff tear (n = 47) and
      the group with rotator cuff tear (n = 43). Satisfactory results were obtained in
      68% of throwing athletes and in 90% of nonthrowing athletes (P < .05) by the Neer
      Rating, whereas only 50% of competitive baseball and softball pitchers had
      satisfactory results. Out impression is that ASD is an acceptable alternative to
      open anterior acromioplasty with comparable results for the treatment of the
      impingement lesion. There were no differences in result in patients who had a
      partial rotator cuff tear and those who had no tear.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7632307
TI  - Effects of tourniquet use in anterior cruciate ligament reconstruction.
AB  - Although tourniquets are used commonly during anterior cruciate ligament (ACL)
      surgery, little data are available regarding their effects on postoperative
      function. This retrospective study evaluated 94 patients who had an
      arthroscopically assisted, autogenous bone-patellar ligament-bone ACL
      reconstruction between 1988 and 1991 at the San Diego Kaiser Hospital. A
      tourniquet was used in 48 patients (T+ group). No tourniquet was used in 46
      patients (T- group). The surgical and postoperative protocols were identical for
      the two groups. There were no bleeding complications. There was no significant
      difference in anesthesia time between the two groups. This study has shown that
      ACL surgery can be performed expeditiously without a pneumatic tourniquet.
      Quadriceps strength recovery after surgery was less in the T+ group at 12 weeks
      after surgery, but there was no significant difference between the groups 52
      weeks after surgery. Difference in thigh girth was greater in T+ group 6 and 12
      weeks after surgery, but there was no significant difference between the groups
      52 weeks after surgery.

PMID- 7632308
TI  - Graft failure in intra-articular anterior cruciate ligament reconstructions: a
      review of the literature.
AB  - There exists a substantial group of patients with unsatisfactory results
      following anterior cruciate ligament (ACL) reconstructions. This may be
      attributable to graft failure. Revision surgery, for the correction of abnormal
      anterior translation of laxity, requires a careful analysis of the causes of
      failure to ensure the success of the salvage procedure. This review attempts to
      present an overview of some of the important studies in the literature pertaining
      to the intraoperative and postoperative factors that probably cause graft
      failure. It was done by initial identification of the articles from a Medline
      database followed by the use of cross references. It shows that failures can be
      minimised by adhering to the correct operative and post-operative techniques
      wherein proper attention to the factors, such as: adequate notchplasty, proper
      tunnel placements, proper tensioning, adequate fixation, optimal selection and
      harvest of the graft, and rehabilitation, are ensured.

PMID- 7632309
TI  - Late rupture of extensor pollicis longus after wrist arthroscopy.
AB  - The first cases of impending rupture of the extensor pollicis longus after wrist
      arthroscopy are reported and the etiology is compared with extensor pollicis
      longus ruptures after nondisplaced or minimally displaced Colles fractures. Both
      cases were treated with extensor indices proprius to extensor pollicis longus
      transfer with good clinical results.

PMID- 7632310
TI  - Risk factors for arthroscopic popliteal artery laceration.
AB  - A case report is presented in which a patient with well-documented pigmented
      villonodular synovitis sustained a disruption of the popliteal artery without
      evidence of penetration of the posterior capsule. The patient had had several
      extensive open synovectomies in the prior 20 years. These included popliteal
      space exposure and dissection. At the time of open arterial repair, multiple
      nodules of pigmented scar were noted densely binding the popliteal artery to the
      surrounding muscle and fascial tissues. The arthroscopist should be aware that
      distension and instrumentation of the knee joint in such patients should be
      performed with extreme care to avoid arterial disruption.

PMID- 7632311
TI  - Pediatric tibial eminence fractures: arthroscopic cannulated screw fixation.
AB  - Two pediatric tibial eminence fractures were arthroscopically reduced and fixed
      with cannulated screws. At 2-year follow-up, anterior tibial translatory laxity
      was normal and the pivot shift test was negative. In one case, the screw
      transgressed the proximal tibial physis; however, neither case showed evidence of
      proximal tibial growth arrest.

PMID- 7632312
TI  - Preparation of an exogenous fibrin clot.
AB  - Exogenous fibrin clot has been proposed to promote the healing of meniscal tears
      in areas of compromised vascularity. We present a method to reproducibly prepare
      a tightly wound exogenous fibrin clot using 5 to 10 mL of blood obtained by
      sterile venipuncture. The technique produces a clot of increased consistency and
      high fibrin content that is adaptable in preparation as a longer, thinner clot or
      a shorter, thicker clot. Clots prepared in this manner will hold suture or can be
      morselized for extrusion through a syringe.

PMID- 7632313
TI  - Removal of the instrument Makar shoulder staple.
AB  - When confronted with the challenge of hardware removal during revision shoulder
      stabilization procedures, specialized instrumentation such as the Instrument
      Makar staple driver/extractor may become necessary. The Synthes DHS/DCS coupler
      screw may be more readily available, and can effectively substitute for the
      Instrument Makar staple driver/extractor.

PMID- 7632314
TI  - Endobutton button endoscopic fixation technique in anterior cruciate ligament
      reconstruction.
AB  - The surgical technique of Endobutton (Acufex Microsurgical, Inc, Mansfield, MA)
      button fixation for anterior cruciate ligament reconstruction is described. This
      technique avoids the potential pitfalls of interference screw fixation, avoids a
      second incision, and is adaptable to a variety of graft materials (autograft or
      allograft bone-patellar tendon-bond and hamstring).

PMID- 7632315
TI  - Condition of graft harvest site.

PMID- 7632316
TI  - Amelioration of hypoxic and hypoglycemic damage to cerebral endothelial cells.
      Effects of heat shock pretreatment.
AB  - Induction of the 70 kDa heat shock protein (HSP70) by hypoxia and/or hypoglycemia
      and the effects of prior heat shock on injury owing to hypoxia and/or
      hypoglycemia were studied in rat cerebral endothelial cells. Hypoxia and/or
      hypoglycemia treatment resulted in increased expression of HSP70 only when such
      treatment was sufficient to cause detectable injury and when the initial
      treatment was followed by exposure of the cells to 24 h of normoxia and
      normoglycemia. Heat shock induced 24 h prior to treatment with 48 h of hypoxia
      slightly reduced endothelial cell damage as measured by fraction of lactate
      dehydrogenase release (10% decrease in injury). There was a more dramatic effect
      of prior heat shock on the moderate damage produced by 12 h of combined hypoxia
      and hypoglycemia (45% decrease), whereas the severe damage produced by 24 h of
      hypoxia and hypoglycemia was decreased by prior heat shock by only 16%. These
      results indicate that the hypoxia and hypoglycemia occurring in conjunction with
      ischemia are more likely to result in heat shock protein expression when there is
      injury to the tissue. Furthermore, heat shock protects cerebral endothelial cells
      from hypoxia and hypoglycemia either by slowing the initial development of injury
      or by delaying the onset of injury.

PMID- 7632317
TI  - Gangliosides modulate proliferation, migration, and invasiveness of human brain
      tumor cells in vitro.
AB  - Gliomas, the most common form of intrinsic brain tumor, are characterized by
      diffuse local invasion of the normal brain structures, irrespective of their
      histological grade of malignancy; a feature that is a major obstacle to
      successful therapy. They generally infiltrate the central nervous system (CNS) as
      individual tumor cells several centimeters beyond the macroscopic tumor margin
      and consequently often recur, after subtotal surgical resection. Factors involved
      in the control of both their proliferation and invasiveness are poorly
      documented. In this work, the role of gangliosides on proliferation of both human
      fetal human brain cells and five cell lines derived from human gliomas with
      different grades of malignancy was investigated. In addition, 8 microns-porosity
      polycarbonate filters were used to study cell motility. In addition, these
      filters were coated with the reconstituted extracellular matrix (ECM) composite,
      Matrigel, to assess invasiveness. The results presented show that gangliosides
      generally exert a proliferation inhibitory effect on fetal brain cells and glioma
      cell lines in vitro and play an important role in promoting glioma cell motility
      and invasiveness. The molecular mechanisms involved in the action of gangliosides
      may prove useful in identifying new targets for an anti-invasion therapy.

PMID- 7632318
TI  - Efficacy of competitive vs noncompetitive blockade of the NMDA channel following
      traumatic brain injury.
AB  - N-methyl-D-aspartate (NMDA) receptor antagonists have been demonstrated widely to
      be neuroprotective in cerebral ischemia, hypoxia, and traumatic brain injury.
      However, although noncompetitive NMDA antagonists have typically proven
      efficacious under all of these conditions, competitive antagonists have not been
      shown to be beneficial following moderate traumatic brain injury. The present
      study has used phosphorus magnetic resonance spectroscopy ([31P]MRS) to examine
      the effects of the competitive antagonist cis-4-(phosphonomethyl) piperidine-2
      carboxylic acid (CGS-19755) and the noncompetitive antagonist dextromethorphan on
      biochemical outcome following fluid percussion-induced traumatic brain injury in
      rats. Five minutes prior to induction of moderate (2.8 +/- 0.2 atm) fluid
      percussion brain injury, animals received either CGS-19755 (10 mg/kg iv),
      dextromethorphan (10 mg/kg iv), or equal volume saline vehicle. [31P]MRS spectra
      were then acquired for 4 h post-trauma and intracellular pH, free magnesium
      concentration, cytosolic phosphorylation potential, and oxidative capacity
      determined. Both CGS-19755-treated animals and saline treated controls
      demonstrated significant and sustained declines in intracellular free magnesium
      concentration and bioenergetic status following trauma. In contrast,
      administration of dextromethorphan significantly attenuated free magnesium
      decline and improved bioenergetic state during the post-traumatic monitoring
      period. These results suggest that the neuroprotective actions of NMDA
      antagonists following traumatic brain injury are associated with attenuation of
      free magnesium decline and that such actions seem to be preferentially mediated
      by noncompetitive blockers.

PMID- 7632319
TI  - Calcium modulates aluminum neurotoxicity and interaction with neurofilaments.
AB  - We examined the influence of calcium on neurotoxicity of AlCl3 and Al-lactate
      toward differentiated NB2a/d1 cells. Apart from induction of perikaryal
      neurofibrillary inclusions, AlCl3 at 1 mM induced no obvious additional signs of
      toxicity when added to culture medium in the presence of the normal medium CaCl2
      content of 1.8 mM, nor when extracellular calcium was decreased by the addition
      to the medium of 0.9 mM EDTA. Increasing the extracellular CaCl2 concentration by
      fivefold was only marginally toxic, but in the presence of AlCl3, reduced viable
      cell numbers by well over 50% as compared to control cultures, and by
      approximately 50% vs fivefold CaCl2 alone. A twofold increase in extracellular
      CaCl2 did not increase the percentage of cells exhibiting Bielschowsky-positive
      perikarya, but induced a near doubling in the percentage of cells exhibiting
      accumulations in the presence of 1 mM Al-lactate. AlCl3 (1 mM) retards the
      electrophoretic migration of NF subunits on SDS-gels. This effect was eliminated
      by withholding CaCl2 from the incubation mixture and including 5 mM EDTA during
      incubation of cytoskeletons with AlCl3. The presence of CaCl2 alone did not alter
      NF migration. These findings underscore the possibility that multiple factors,
      including those that compromise general neuronal homeostasis, may contribute to
      neurofibrillary pathology.

PMID- 7632320
TI  - Ganglioside GM1 prevents N-methyl-D-aspartate neurotoxicity in rabbit hippocampus
      in vivo. Effects on calcium homeostasis.
AB  - Microdialysis was used to apply 1 mM N-methyl-D-aspartate (NMDA) for 20 min to
      the hippocampus of rabbits, control and pre-treated with GM1 ganglioside (im
      injections of 30 mg/kg for 3 d, twice a day). Concentrations of ionized Ca2+ and
      6-keto prostaglandin F1 alpha (6-keto PGF1 alpha)-immunoreactive material in the
      dialyzates and 45Ca and [14C]sucrose efflux from the prelabeled hippocampus were
      determined. After 24 h, the morphology of the hippocampal neurons was examined.
      In control animals, the application of NMDA resulted in 25% decrease in Ca2+
      concentration and in 1000% increase in 6-keto PGF 1 alpha concentration in the
      dialyzates. A 30% decrease in 45Ca efflux was accompanied by 20% increase in
      [14C]sucrose efflux, reflecting a corresponding reduction of the extracellular
      space volume. A degeneration of CA1 pyramidal neurons in the vicinity of a
      microdialysis probe was observed. In GM1-treated rabbits the NMDA-induced
      decrease in Ca2+ concentrations in the dialyzates was not reduced significantly,
      whereas a 70% stimulation of 45Ca efflux was noted, with a concomitant 40%
      reduction of 6-keto-PG F1 alpha release. NMDA-evoked increase in [14C]sucrose
      efflux did not differ from the control. In these animals CA1 neurons were well
      preserved. These results indicate that the pretreatment with GM1 results in
      activation of calcium extrusion from the NMDA-stimulated rabbit hippocampal
      neurons that alleviates destabilization of calcium homeostasis and reduces NMDA
      evoked neuronal injury.

PMID- 7632321
TI  - A biochemical and ultrastructural evaluation of the type 2 Gaucher mouse.
AB  - Gaucher mice, created by targeted disruption of the glucocerebrosidase gene, are
      totally deficient in glucocerebrosidase and have a rapidly deteriorating clinical
      course analogous to the most severely affected type 2 human patients. An
      ultrastructural study of tissues from these mice revealed glucocerebroside
      accumulation in bone marrow, liver, spleen, and brain. This glycolipid had a
      characteristic elongated tubular structure and was contained in lysosomes, as
      demonstrated by colocalization with both ingested carbon particles and cathepsin
      D. In the central nervous system (CNS), glucocerebroside was diffusely stored in
      microglia cells and in brainstem and spinal cord neurons, but not in neurons of
      the cerebellum or cerebral cortex. This rostralcaudal pattern of neuronal lipid
      storage in these Gaucher mice replicates the pattern seen in type 2 human Gaucher
      patients and clearly demonstrates that glycosphingolipid catabolism and/or
      accumulation varies within different brain regions. Surprisingly, the cellular
      pathology of tissue from these Gaucher mice was relatively mild, and suggests
      that the early and rapid demise of both Gaucher mice and severely affected type 2
      human neonates may be the result of both a neurotoxic metabolite, such as
      glucosylsphingosine, and other factors, such as skin water barrier dysfunction
      secondary to the absence of glucocerebrosidase activity.

PMID- 7632323
TI  - Tumor necrosis factor alpha (TNF-alpha) is involved in the pathogenesis of the
      panencephalopathic type of Creutzfeldt-Jakob disease.

PMID- 7632324
TI  - Ultrastructural localization of heme oxygenase-1 to the neurofibrillary pathology
      of Alzheimer disease.

PMID- 7632322
TI  - Decrease of D-loop frequency in heart and cerebral hemispheres mitochondrial DNA
      of aged rat.
AB  - A quantitative analysis of the frequency of the supercoiled mitochondrial DNA
      molecules containing the D-loop in rat heart and cerebral hemispheres, at
      different ages, is presented. Both tissues of aged animals exhibit a remarkable
      reduction in the content of super-coiled D-loop containing molecules compared to
      the adults. This alteration could be responsible for the age-dependent reduction
      of mitochondrial DNA transcription previously observed in rat brain and heart.

PMID- 7632325
TI  - Evolutive levels of NGF in neurodegenerative disorders.

PMID- 7632326
TI  - Long-term adrenalectomy. Effect on cognitive behavior.

PMID- 7632327
TI  - Neurorestorative techniques as experimental approach to Alzheimer disease
      treatment.

PMID- 7632328
TI  - Early loss of neurons and axon terminals in scrapie-affected mice revealed by
      morphometry and immunocytochemistry.

PMID- 7632329
TI  - Neuronal plasticity and Parkinson disease.

PMID- 7632330
TI  - Pathological and mineral status investigations in quadriplegic lambs.

PMID- 7632331
TI  - Immune response in Cuban epidemic neuropathy.

PMID- 7632332
TI  - Platelet-activating factor production by human fetal microglia. Effect of
      lipopolysaccharides and tumor necrosis factor-alpha.
AB  - Since platelet-activating factor (PAF) exerts neurotoxic effects on brain cells,
      we explored the possibility of PAF production by human fetal microglial cells in
      vitro. PAF content in pure cultures was assayed and characterized in basic
      conditions, and after stimulation with growth factors and cytokines. Results
      showed that microglia cells synthesized PAF when challenged with tumor necrosis
      factor-alpha and lipopolysaccharides, whereas other molecules, such as gamma
      interferon or basic fibroblast growth factor, were ineffective. The induced PAF
      production was concentration- and time-dependent. These results are in line with
      the hypothesis that microglia can start a cascade of events leading to tissue
      damage, thus playing a central role in the pathogenesis of several central
      nervous system diseases.

PMID- 7632333
TI  - Neurodegenerative Disorders, Common Molecular Mechanisms. Ocho Rios, Jamaica,
      April 10-15, 1994. Proceedings and abstracts.

PMID- 7632334
TI  - Procamallanus diacanthum n. sp. (Nematoda: Camallanidae) from the intestine of
      marine fish Johnius diacanthus (Lacepede), India.
AB  - The present paper describes a new species of a nematode of the family
      Camallanidae Railliet et Henry, 1915 from the intestine of marine fish Johnius
      diacanthus (Lacepede) from Kalingapatnam coast. These specimens do not agree with
      the description of the hitherto described species of the genus. Hence a detailed
      description and status of the specimens are given in this paper. The new species
      is characterized by body measurements, structure of spiral thickenings, nerve
      ring and excretory pore position, absence of gubernaculum, number and arrangement
      of caudal papillae, length of spicules and shape of tail end. Thus it could be
      considered as a new species. Procamallanus diacanthum.

PMID- 7632335
TI  - Description of a new species of the genus Camallanus Railliet et Henry, 1915
      (Nematoda: Camallanidae) from freshwater fish, Barbus (Puntius) ticto (Gunther)
      from Krishna River, Andhra Pradesh, India.
AB  - A new species of a nematode of the family Camallanidae Railliet et Henry, 1915
      from the ovary of freshwater fish, Barbus (Puntius) ticto (Gunther) caught off
      the Krishna River at Vijayawada (Andhra Pradesh) is described. Description is
      based on two male and two female specimens from a large number of hosts examined.
      The specimens do not agree with descriptions of known species of the genus
      Camallanus, hence a new species Camallanus praveeni has been erected to
      accommodate the present specimens. The new species could be distinguished by body
      measurements, in the nature of tridents, position of nerve ring and excretory
      pore, position and length of spicules, number and arrangement of caudal papillae,
      vulva position and shape of tail end.

PMID- 7632336
TI  - [Evaluation of ELISA-IgG test using a purified antigen in the diagnosis of human
      hydatidosis].
AB  - An enzyme-linked immunosorbent assay (ELISA) was developed for the detection of
      IgG antibodies to purified sheep hydatic cyst fluid antigen in 56 sera of
      confirmed cases of hydatidosis. The cut-off value was determined using serum
      samples from 80 healthy persons, employing two serum dilutions (1:100 and 1:500)
      with two and three standard deviations (SD). This assay was compared with the
      indirect hemagglutination test (IHAT). The sensitivity of ELISA-IgG was 94.3% for
      hepatic cysts and 92.9% for pulmonary cysts, whereas the values for IHAT were
      77.1 and 64.3% respectively. According to Mac Nemar test, both method presented
      statistical significance (p < 0.05). In order to find out the specificity,
      additional 70 serum samples from individuals with other parasitoses, such as
      cysticercosis (30), trichinosis (26) and fascioliasis (14) were also tested. IHAT
      presented a specificity of 92.7% and for ELISA-IgG the specificity using a cut
      off of mean + 3 SD was 99.3 and 100.0% with sera dilution of 1:100 and 1:500
      respectively when a cut-off of mean + 2 SD was considered, we found a specificity
      of 91.3 and 97.3% for 1:100 and 1:500 dilutions. The use of ELISA-IgG and
      purified antigen in the diagnosis of human hydatidosis is discussed.

PMID- 7632337
TI  - [Chronic Chagas cardiomyopathy. Serologic and anatomopathologic study].
AB  - In order to contribute to a better knowledge of the chronic chagasic
      myocardiopathy, a post-mortem serological and anatomopathological study of
      Chagas' disease was carried out in 40 corpses. Between november 1987 and august
      1988, autopsies were performed at the Pathological Anatomy Service of Antofagasta
      Regional Hospital and the Legal Medicine Section of the Ministry of Justice in
      Antofagasta. Positive postmortem chagasic serology, by using an indirect
      immunofluorescence test in pericardial fluid, was confirmed in three cases, among
      which the study of the histopathology of the cardiac muscle showed "Trypanosoma
      cruzi type" elements of the damage. The macroscopic morphological study did not
      show relevant findings. Results reveal the need to implement anatomopathological
      study systems for routines which contribute to evaluate the chagasic etiology as
      a cause of death among population of the endemic Chilean area.

PMID- 7632338
TI  - [Human hydatidosis in Valdivia, Chile: retrospective survey at the Valdivia
      Regional Hospital. 1987-1991].
AB  - A retrospective hospital survey of surgically confirmed cases of hydatidosis in
      the province of Valdivia was carried out. Data were provided by the Valdivia
      Regional Hospital and a five year (1987-1991) period was covered. Morbidity,
      mortality and case fatality rates were calculated. Descriptive epidemiological
      characteristics of the disease were determined. In the period studied, 137 new
      cases were registered. The incidence rate for the period was 9.1 per 100,000
      inhabitants. The mortality rate was 0.2 per 100,000 inhabitants and the average
      fatality rate was 2.2%. The over-all sex distribution was 51.8% for females and
      48.2% for males. The age group 10-19 years was the most affected by the disease
      (30.7%). The distribution according to activity revealed a higher proportion of
      house-wives (29.2%) and students (23.2%) with the disease. Hydatidosis was more
      frequent in Valdivia (23.4%), Panguipulli (17.5%) and La Union (15.5%) and in
      patients from rural areas (73.7%).

PMID- 7632339
TI  - [Trichinosis outbreak in Purranque County, X Region, Chile. October-November,
      1992].
AB  - An outbreak of trichinosis occurred in Purranque County, X Region, Chile, between
      october and november of 1992, which involved 36 persons. The incubation period,
      determined by the clinical picture and laboratory assays, fluctuated between 10
      and 12 days. Myalgias (88.9%) and palpebral oedema (86.1%), were the most
      important symptoms, followed by fever (44.4%) and headache (33.3%). Eosinophils
      count ranged from two to 42% the first week, and this value raised to 55% the
      second week of the outbreak. Anti-Trichinella spiralis antibodies were determined
      by some serological tests such as: precipitin test (PT), bentonite flocculation
      test (BFT) and indirect hemagglutination test (IHAT) in sera from 28 patients at
      the beginning of the outbreak. PT was positive in 46.4% of the cases, followed by
      IHAT (21.4%) and BFT (3.6%). After 15 days, the three tests were performed in
      sera from 12 patients. At that time, the positivity was elevated in all of them:
      PT (100.0%), BFT (66.7%) and IHAT (91.7%). It is believed that the outbreak had
      its origin in infected pork meat that was consumed raw or insufficiently cooked
      without a previous veterinary inspection.

PMID- 7632340
TI  - [Seroepidemiological investigation of various tissue helminthiasis, by means of
      indirect hemagglutination test, in Lonquimay County, Chile].
AB  - In order to have a present perspective on the prevalence on the epidemiology of
      some tissue helminthiasis in Lonquimay County, southern Chile, in 1993 a
      seroepidemiological survey, by means of an indirect hemagglutination test (IHAT)
      for hydatidosis, cysticercosis and trichinosis was undertaken. In 11 (1.2%), 10
      (1.1%) and 6 (0.6%) out of 945 examined persons, most of them from rural areas,
      the corresponding IHAT resulted positive. Additionally, radiographic and
      ecotomographical studies for thorax and abdomen respectively were performed to
      the 11 individuals with serology positive for hydatidosis: whereas all the
      thoracic radiographies resulted negative, liver hydatic cysts were detected in
      five persons, who latter on were submitted to surgery. Prevalence rates of
      hydatidosis in Lonquimay are among the highest regional and national values.

PMID- 7632342
TI  - Field homogeneity of bevelled intraoperative electron beam cones: the influence
      of virtual focus surface distance.
AB  - Field flatness of bevelled intraoperative electron therapy cones were evaluated
      from dose profiles, taken at dmax, both in the longitudinal plane (long axis
      direction) and the transversal plane (short axis direction), and were found to
      depend strongly on the setting of the x-ray collimators. Dose gradients in the
      longitudinal plane of 10-12% were found for collimator settings of 5 mm larger
      than the cone diameter for low energies, while the dose gradient were smaller for
      higher energies, both decreasing with larger collimator setting. The dose
      increase, relative to the central dose, of the hot spots observed in the profile
      of the transversal plane were in the range of 5-10% for high energies and large
      collimator settings, decreasing to less than 3% for low electron beam energies
      and smaller collimator setting. A decrease in virtual focus to surface distance
      (VFSD) was found to accompany the increasing dose gradient in the longitudinal
      plane with decreasing collimator setting, this due to increased scatter of
      electrons at collimator level. Increasing scatter with smaller collimator setting
      is also indicated by the increase in photon contamination ranging from 1-2.5% for
      low energies and 3.5-5% for high energies.

PMID- 7632341
TI  - [Frequency of intestinal protozoosis in the Mexican Republic].
AB  - The reports about the frequency of intestinal protozooses found in humans who
      live in different localities of the Mexican Republic, are in general uncertain
      and not trustworthy, possibly because very few and poor epidemiological surveys
      have been undertaken in the country. However, with the few trustful studies
      carried out (1981 to 1991), it is possible in Mexico, to verify that amibiasis,
      giardiasis and criptosporidiosis are present with significant percentages of
      infection: 30.6, 22.3 and 39.3% respectively. With the summary of the researches
      analyzed in this article, one can conclude that human infections by intestinal
      protozoa in the Mexican Republic, at the present time, are almost as frequent as
      in past decades. This occurs because still remain the factors that contribute to
      the persistence and spreading of intestinal parasites, such as fecalism, poor
      hygienic and alimentary habits, within a deficient environmental sanitation.

PMID- 7632343
TI  - A CT-based simulation for head and neck tumors in centers without CT-simulator
      and 3D-planning system.
AB  - We present a special CT-based simulation technique to optimize the radiotherapy
      treatments in head and neck tumors. On an immobilization device, some CT
      hyperdense markers are placed. Real-size CT slices are performed every 5 mm with
      the patient in the treatment position with the immobilization system. This study
      permits a more accurate knowledge of the gross tumoral volume and an optimization
      of the planning treatment.

PMID- 7632344
TI  - Comparison of treatment plans for irradiating adenocarcinoma of the prostate.
AB  - In a clinic with multiple megavoltage beams (Co-60, 6 MV, 10 MV, 18 MV)
      available, the optimal dose distributions depends on the radiation technique,
      patient size, and beam energy. To determine optimal dose distributions for
      external beam irradiation for patients with localized adenocarcinoma of the
      prostate, we investigated the dependence of beam energy, treatment technique, and
      patient size. Various radiation isodose plans were prepared at the central plane
      of the treatment field using computerized tomography scans of the pelvis for
      small, medium, and large patients. The dose uniformity in the target volume, the
      dose received by sensitive tissues such as bladder, rectum, and femoral heads,
      and the irradiated volume of these normal tissues were used as the criteria for
      comparing the plans. In all cases, the target volume was within the 95% isodose
      line with good dose uniformity (+/- 5%, of the prescribed dose). The volume of
      the rectum and bladder enclosed within the 90% isodose curve depended on the
      choice of the beam energy and the treatment technique for different patient
      sizes. For the small size patient the optimal dose distribution was achieved by
      using 10 MV box and arc or oblique boost. For the medium size patient, using 18
      MV X-rays with box technique and oblique boost gave the optimal treatment plan.
      For the large size patient, using 18 MV or 10 MV X-rays box technique with arc
      boost were both acceptable.

PMID- 7632345
TI  - A simple manual method of repositioning small bowel during pelvic irradiation.
AB  - Small intestine is often unnecessarily irradiated during radiotherapy because it
      lies near tumor volumes and thus may be dose limiting. Repositioning of normal
      tissues can sometimes be accomplished by mechanical rather than invasive surgical
      techniques. At our institution, physical displacement of small bowel tissues was
      carried out on a population of patients with good result. Patients suffering from
      prostatic, cervical, and rectal carcinoma were treated using a custom built and
      padded block composed of rigid Styrofoam. The block, in most cases, successfully
      displaced significant amounts of healthy tissues from treatment fields. Maximum
      displacement of bowel was accomplished at the time of simulation using
      fluoroscopy and manual positioning of the device. The optimum displacement
      position and location of the Small Bowel Displacement Device (SBDD) were recorded
      by means of orthogonal radiographs. The device was affixed to a piece of mylar
      that had been previously scribed with an X and Y coordinate system, which could
      be used to permanently anchor the SBDD to its position of maximum displacement.
      Displacements of as much as 4.0 to 5.0 cm were noted on most patients. Patients
      generally tolerated the device well as long as they were able to lie prone.
      Patients with recent abdominal surgery were less likely to tolerate the SBDD, and
      omental slings or meshes generally precluded movement of the small bowel.

PMID- 7632346
TI  - A simple device for prostate and rectal localization in radiation therapy.
AB  - A simple device for prostate and rectum localization in radiation therapy may be
      constructed as follows: first, dental wax is used to make up a shape of the
      rectal probe. Second, dental stone is used to make a two-piece mold by molding
      the dental wax probe. Third, using the mold, the rectal probe is made from a
      mixture of silicone and barium. The final step involves the attachment of the
      "plug," which is made of aluminum. From the simulation films for the prostate
      setup, the location of the anterior wall of the rectum, anal sphincter, and anal
      verge can easily be identified, such that the appropriate regions are shielded
      accordingly. A CT scan with the probe in the rectum did not give too much
      artifacts from the barium/silicone mixture. The rectal probe with the plug is
      useful for localizing the prostate more accurately, compared with using the other
      rectal localization techniques such as barium injection or some rectal markers.

PMID- 7632347
TI  - Proposed semi-analytical formulae for the determination of (L/rho)medair and
      Prepl for electron beams as used in radiotherapy.
AB  - To convert an ionization measurement to absorbed dose, the TG-21, the IAEA, and
      the TG-25 protocols for the calibration of high energy electron therapy machines
      demand an accurate knowledge of the mean restricted collision mass stopping power
      ratio, (L/rho)medair, and the electron fluence correction factor, Prepl. This
      paper presents a semi-analytical expression to calculate (L/rho)medair at depths
      in the range of 0 to 30 g/cm2 and for any energy in the range of 4-60 MeV, for
      water, polystyrene, and acrylic relative to air, and another expression to
      calculate Prepl for any cylindrical ionization chamber with an inner diameter in
      the range of 3 to 7 mm. The published values for (L/rho)medair were fitted to a
      single analytical expression with 10 coefficients using a nonlinear least square
      routine. Another expression with 4 coefficients was used to fit the electron
      fluence correction factor, Prepl, for cylindrical ionization chambers, as a
      function of chamber diameter and the mean electron energy at depth of
      measurement. In the electron energy range of 4-60 MeV, and for all published
      depths, the calculated (L/rho)medair values agree with the published values
      within +/- 1% in 99% of the cases. The calculated Prepl values agree with the
      tabulated values within +/- 1% in all of the cases. The proposed equations now
      allow one to use a computer to calculate the values of (L/rho)medair and Prepl
      accurately, doing away with the time-consuming procedure of interpolating between
      values from tables during the routine calibration of high energy electron therapy
      machines.

PMID- 7632348
TI  - Application of the "bioeffects" algorithm of a treatment planning system.
AB  - In this study, both a four-field box and two-field AP/PA treatment plan are
      combined with two insertions of Cs-137 in a tandem and ovoids setup, to evaluate
      the bioeffects program of a treatment planning system. External beam energies
      studied are 18 and 6 MV. It is shown that there is a slight difference in the 50
      70 time dose fractionation (TDF) isolines when comparing 6 MV and 18 MV, for the
      AP/PA setup. There is practically no difference for TDF isoline values larger
      than 80 for both energies with either the four-field or the two-field setup. This
      is because the brachytherapy contributed the majority of the dose to the regions
      near the applicator and the TDF values reflect the higher dose delivered by the
      brachytherapy relative to the external beams in that region. For this simple
      evaluation of the bioeffects program, the combination of the external beam plan
      and the brachytherapy plan does not give us enhanced information on the
      effectiveness of the plan.

PMID- 7632349
TI  - A simple technique for fabrication of transmission block for concomitant
      treatment of bilateral anterior inguinal lymphatics and pelvic/perineal
      structures.
AB  - The efficacy of transmission block technique with contiguous photon irradiation
      of inguinal as well as pelvic and perineal structures has been reported in
      literature. In this paper, a simple and accurate method for the proper
      fabrication of transmission block has been described and also demonstrated to be
      effective and useful. The procedures for a precise geometrical alignment and dose
      verification are also detailed.

PMID- 7632350
TI  - Use of a lucite beam spoiler for high-energy breast irradiation.
AB  - Treatment planning for breast cancer is a challenge for bridge separations
      greater than 24 cm. protocols require dose homogeneity to the breast parenchyma
      to 10% while maintaining good cosmesis (skin sparing). Low-energy beams (6 MV or
      lower) may not achieve protocol specifications because of lateral or medial hot
      spots. The buildup region for high-energy beams (i.e., 18 MV) may lead to
      underdosing in the superficial regions. Adding bolus will pull the isodoses to
      surface, surrendering skin sparing. A spoiler will increase the contribution of
      scattered medium energy electrons and photons, thereby increasing superficial
      dosing and maintaining skin sparing due to displacement of the spoiler from the
      skin. We chose Lucite as the spoiler material for our 18-MV beam. Buildup
      measurements were performed with a parallel-plate ionization chamber to find the
      optimal spoiler thickness of 18 mm at a spoiler-to-skin distance of 22 cm. A
      breast phantom was designed allowing thermoluminescent dosimeter measurements.
      The spoiler has increased the percent depth dose from the depths of 0.5 cm to 3.0
      cm to mimic those delivered by a 6 MV beam, while the relative skin dose was held
      to 50%. Our treatment schema is typically 6-MV photons with customized
      compensation for half or more of the fractions and uncompensated 18-MV photons
      with the spoiler for the remaining fractions. The spoiler may be used in
      conjunction with thin bolus (1.0 cm) for therapeutic dosing to the skin (scars,
      inflammatory disease, etc.). The treatment plans have maintained dose homogeneity
      for large patients, without consequence of skin reaction.

PMID- 7632351
TI  - Applications of asymmetric collimation on linear accelerators.
AB  - Frequency of use of asymmetric collimation (AC) at an academic radiation oncology
      center equipped with AC-capable linear accelerators was determined, and the type
      of use was cataloged. Records of patients beginning radiation treatment at U.C.
      Davis Cancer Center within a 3-month period (3/1/92 to 5/31/92) were reviewed.
      Forty-seven percent of 102 patients and 56% of 123 courses of treatment involved
      AC. Six common uses of AC were identified: beam-split field matching, planned
      boosts, other field size changes, adjustments to match divergent fields,
      matchline feathering, and opposed tangential fields. This study demonstrates that
      asymmetric collimation is a useful and powerful clinical treatment tool with
      widespread applications to radiation therapy.

PMID- 7632352
TI  - Implementation of total skin electron therapy using an optional high dose rate
      mode on a conventional linear accelerator.
AB  - A technique for total skin electron therapy (TSET) has been implemented using a
      standard accelerator that has been equipped with an optional special procedures
      mode to permit high dose-rate therapy with a 6-MeV electron beam. Patients are
      treated in a standing position using dual angled fields at a source to skin
      distance of 3.6 m. Dosimetric characteristics of the dual field technique were
      investigated for the 6-MeV beam as well as for a lower energy beam produced by
      the introduction of an acrylic beam degrader. A treatment stand, which
      incorporates the degrader in addition to devices used for patient support and
      shielding, is described. Acceptable beam uniformity and depth dose have been
      achieved while maintaining a low level of x-ray contamination. Treatment times
      are reasonably short since the output of the machine in the high-dose-rate mode
      is 25 Gy/min at the isocenter. Beam uniformity, dose rate, and x-ray
      contamination are relatively unaffected by the presence of the beam degrader if
      it is positioned near the treatment plane. The high dose-rate electron option is
      a useful treatment mode that provides the advantage of reduced treatment times
      while retaining proper functioning of all accelerator dosimetry systems and
      interlocks. Use of a dual field technique permits TSET in a treatment room of
      standard dimensions. The machine is easily set up for treatment, and patient
      setup is simplified through use of a customized support system.

PMID- 7632354
TI  - Huitlacoche (Ustilago maydis) as a food source--biology, composition, and
      production.
AB  - Huitlacoche is the ethnic name applied to the young fruiting bodies (galls) of
      the fungus Ustilago maydis, which causes common smut of maize (Zea mays L).
      Biologists and agronomists have historically used U. maydis as a model to study a
      wide array of genetic, physiological, ecological, and phytopathological
      phenomena. In Mexico and other Latin American countries, huitlacoche has been
      used traditionally as human food, being highly regarded as an interesting dish or
      condiment. The food potential of huitlacoche is described here in terms of its
      chemical composition, which includes carbohydrates, proteins, fats, vitamins, and
      minerals. In addition, essential amino acids (especially lysine) and fatty acids
      (linoleate) are present in huitlacoche in considerable levels, adding to its
      nutritional attributes. The feasibility of growing U. maydis in submerged
      agitated culture has yielded a variety of fermentation products, including
      essential amino acids, proteins, vitamins, and flavorings, among others. Recent
      interest in developing huitlacoche as a cash crop has come from increasing
      acceptance by the North American public, who prize it as a new delicacy. However,
      research efforts are still needed to determine the biological factors involved in
      the establishment of U. maydis as a pathogen on the maize plant. This review
      deals with the role of huitlacoche as a food source, implicating the biological
      components that will determine the development of technologies for large scale
      production.

PMID- 7632355
TI  - Evaluation of the integrated time-temperature effect in thermal processing of
      foods.
AB  - In this review, current methods used to evaluate the integrated impact of time
      and temperature upon preserving a food product by a heat treatment are
      considered. After identifying the basic premise any preservation scheme shall
      meet, the central role of a feasible description for the heat activation kinetics
      of microorganisms, their spores, and other quality attributes are stressed.
      Common concepts to quantify a thermal process are presented. Shortcomings of the
      prevalent evaluation methods are highlighted and attention is given to the
      development, restrictions, and possibilities of time-temperature-integrators as
      "new" evaluation tools to measure the impact of a "classical" in-pack heat
      treatment and more modern heating techniques such as continuous processing of
      solid/liquid mixtures on foods.

PMID- 7632353
TI  - Nutritional factors and colon cancer.
AB  - During the last 2 decades, substantial progress has been made in understanding
      the relationship between dietary constituents and the development of colon cancer
      in man. Unlike studies of cancer among smokers and nonsmokers, nutritional
      epidemiologic studies are confronted with the inherent difficulty of assessing
      reasonably precise exposures. The lack of consistency between international
      correlation studies and case-control studies does not necessarily negate a
      dietary etiology of colon cancer because these inconsistencies may have arisen,
      at least in part, from methodological limitations. Some of these deficiencies in
      epidemiological studies of diet and cancer have been corrected; recent case
      control studies demonstrated that high dietary fat is a risk factor for colon
      cancer development and that an overall increase in intake of foods high in fiber
      might decrease the risk for colon cancer. The results of epidemiologic studies
      may be assumed to present conservative estimates of the true risk for cancer
      associated with diet. The populations with high incidences of colon cancer are
      characterized by high consumption of dietary fat, which may be a risk factor in
      the absence of factors that are protective, such as whole-grain cereals and of
      other high fiber. Laboratory-animal model studies have shown that certain dietary
      lipids and fibers influence tumorigenesis in the colon. The data of metabolic
      epidemiological and laboratory-animal model studies are sufficiently convincing
      with respect to the enhancement of colon cancer by type of fat and protection by
      certain dietary fibers.

PMID- 7632356
TI  - Radiosurgery for brain tumours: is there a proven benefit?

PMID- 7632357
TI  - Haemangiopericytoma: a clinical and radiological comparison with atypical
      meningiomas.
AB  - A small number of haemangiopericytomas (HPCs) are compared with a group of cases
      labelled as atypical meningiomas (AMs) extracted from our records over a 10-year
      period. There was close convergence between the two groups in terms of clinical
      presentation. Radiologically, they were quite different. HPCs subjected to
      angiography demonstrated a major vascular supply from branches of the internal
      carotid or vertebral arteries, whereas this was not a feature of the meningioma
      group. Half the HPCs arose from the lateral petrosal attachment of the tentorium;
      all the meningiomas were parasagittal. The HPCs did not prove to be more
      formidable technical challenges than the meningiomas: the operative blood loss
      was much the same in both. The same number of recurrences and deaths occurred in
      the two groups at approximately the same interval during the follow-up period,
      making both conditions equally grave in terms of prognosis.

PMID- 7632358
TI  - Results of surgery in children with cerebral cavernous angiomas causing epilepsy.
AB  - Epilepsy is the most frequent presenting symptom of cerebral cavernous angiomas
      or cavernomas, and surgical removal of these vascular malformations is considered
      the treatment of choice in patients with intractable or long-standing seizures,
      or in those with poor compliance to medical therapy. In this paper the results of
      surgical treatment in 11 children with seizures from cerebral cavernomas are
      reported. Surgery for deep-seated cavernomas was aided in 3 cases by a
      stereotactic localization technique, that allowed a limited approach with minimal
      brain damage. Major morbidity and mortality were absent; follow-up ranged between
      1 to 16 years. Improved seizure control was seen in all the patients: eight (72%)
      became seizure-free with the same preoperative therapy; one became seizure-free
      with a lower drug dosage, and two (18%) were seizure-free without medical
      therapy. The removal of cavernomas prevented the risk of haemorrhages or further
      deficits from growth and, above all, avoided spreading and autonomization of the
      epileptogenic area induced by the cavernoma.

PMID- 7632359
TI  - p53 immunoreactivity in astrocytomas and its relationship to survival.
AB  - p53 is a putative tumour suppressor gene implicated in a wide range of human
      malignancies. Mutation of p53 gene results in a more stable product and increased
      quantities of p53 protein in the cell. Thus, unlike the normal situation, mutated
      p53 is detectable by immunohistochemistry. We stained frozen sections of 74
      astrocytomas with two antibodies to p53, PAb 1801 and PAb 421. Overall 18/74
      (24%) of astrocytomas showed p53 immunoreactivity. Fifteen of 47 (32%) grade IV
      were p53 immunopositive, as were 3/16 (19%) grade III, 0/7 (0%) grade II and 0/4
      (0%) grade I astrocytomas. These findings are in agreement with previous studies
      in showing relatively greater numbers of high grade than low grade p53
      immunopositive tumours. Although we found an expected difference in survival
      according to grade, there was no significant difference in survival (p > 0.1)
      between p53 immunopositive and immunonegative tumours. We conclude that, whilst
      p53 undoubtedly plays an important role in the molecular 'chain' leading to
      malignancy in some astrocytomas, within tumours of comparable grade it does not
      appear to influence survival.

PMID- 7632360
TI  - Visual outcome after transsphenoidal surgery for pituitary adenomas.
AB  - We have reviewed the records of 53 patients with visual impairment secondary to
      pituitary macroadenomas and studied the visual outcome after surgery. After
      transsphenoidal procedures visual field defects improved in 89% of the patients
      and visual acuity improved in 82%. There were 13 cases of acute symptomatic
      intratumoural haemorrhage (pituitary apoplexy) in this series. After surgery,
      visual defects improved in all these cases even when the delay between the onset
      of symptoms and surgery was long.

PMID- 7632361
TI  - Prophylaxis against thromboembolism in neurosurgical patients: a survey of
      current practice in the United Kingdom.
AB  - Venous thromboembolism is a life threatening, but preventable complication of
      major surgery. Many neurosurgical patients are at high risk of developing
      thromboembolic disease. A postal survey was undertaken of 44 UK neurosurgical
      centres to assess the use of physical and pharmacological methods of prophylaxis
      against thromboembolism. Thirty-five replies were received from 31 centres.
      Seventy-seven per cent of units used antiembolism stockings (TEDs) for elective
      surgery and 37% for emergency surgery; in approximately two-thirds of these units
      TEDs constituted the sole method of prophylaxis used during both elective and
      emergency surgery. Intermittent pneumatic compression (IPC) was utilized in 37
      and 11% of units for elective and emergency surgery, respectively. Subcutaneous
      heparin was used in 32% of units perioperatively including 6% of emergency cases.
      These findings suggest that neurosurgical patients, who are at moderate to high
      risk of developing thromboembolic complications, may not receive effective
      prophylaxis; those undergoing emergency neurosurgery are less likely to receive
      any form of prophylaxis.

PMID- 7632362
TI  - Glycerol versus radiofrequency rhizotomy--a comparison of their efficacy in the
      treatment of trigeminal neuralgia.
AB  - Ever since the anatomical basis of trigeminal neuralgia has been postulated to be
      vascular compression, microvascular decompression has been gaining acceptance as
      the definitive treatment of the condition. However, the majority of patients are
      over 50 years of age, and posterior fossa procedures carry significant risk in
      terms of morbidity and mortality. Radiofrequency and glycerol rhizotomy are the
      two procedures commonly performed in patients considered unsuitable for posterior
      fossa craniectomy. This study attempts to assess the relative merits and demerits
      of these two procedures and seeks to establish indications for each. It is felt
      that glycerol rhizotomy is better as the first line treatment.

PMID- 7632363
TI  - Primary cerebral gliosarcoma: report of 17 cases.
AB  - A retrospective study of 17 cases of primary cerebral gliosarcoma is presented.
      These uncommon highly aggressive intracranial neoplasms were seen at the Royal
      Preston Hospital, between 1973 and 1992. The patients' ages ranged from 21 to 73
      years (mean 52), nine were males and eight were females. They presented with
      signs and symptoms of a rapidly expanding brain tumour. The diagnosis was
      suspected on radiological findings and confirmed by histological examination.
      Treatment involved surgical excision in 15 cases and biopsy in two followed by
      radiotherapy. Chemotherapy was given in three cases. Despite active management,
      median survival was only 9 months. The clinical, radiological and pathological
      features of these lesions are highlighted with emphasis on combined
      histochemistry and immunohistochemistry. The features of gliosarcoma and
      glioblastoma are compared and contrasted.

PMID- 7632364
TI  - The Apache II scoring system in neurosurgical patients: a comparison with simple
      Glasgow coma scoring.
AB  - In order to compare the predictive value of the Apache II, the Glasgow Coma Scale
      and Revised Trauma Scoring systems in relation to outcome in a neurosurgical
      department high dependency unit (HDU), all 109 patients entering the unit under
      the care of one consultant were studied. All patients in the HDU were self
      ventilating, so that motor responses were not suppressed by muscle relaxants or
      sedation. Initial Minimum and Maximum Glasgow Coma Scale Scores, Revised Trauma
      Score, Apache II and the Apache minus neurological weighting (Apache-NW) scores,
      were compared as predictors of outcome (as assessed by the Glasgow Outcome Score
      at 6 months). Twenty-eight patients had a bad outcome, i.e. Glasgow Outcome
      Scores 1-3, and 72 individuals a good outcome, i.e. scores 4 or 5. Statistical
      analysis was by the Spearman Ranked Correlation Test, and comparison of Receiver
      Operational Characteristics Curves. Data were complete on 100 patients (91.7%)
      and show the Maximum Glasgow Coma Score, followed by the Apache II score, as the
      best predictors of outcome analysed. This was also true if all patients except
      those with head injury were analysed as a group. All scoring systems were
      significantly better predictors of outcome in the head injured patient. For this
      group, Apache II had an outcome predictive value of 97% compared with 93% for
      initial and 95% for minimum GCS. Removing the neurological weighting from Apache
      II weakened its predictive ability in all patients, emphasizing that it is the
      neurological status of the patient which best predicts overall functional
      outcome. Apache II data are also much more time-consuming to collect than GCS
      data.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7632365
TI  - Preoperative shunts in suprasellar tumours.
AB  - A series of 22 cases of large suprasellar tumours was studied retrospectively.
      These patients had undergone a preoperative shunt to facilitate surgical exposure
      of the tumour and to reduce intracranial pressure in critically ill patients. Our
      observations on the clinical progress of these patients following the shunt is
      analysed. Nine patients worsened to a varying degree following insertion of the
      shunt. Seven patients became drowsy, one developed worsening of vision and a
      hemiparesis, and one became an akinetic mute. The worsening was probably related
      to alteration of intracranial pressure dynamics and resultant compression in the
      hypothalamic region by subtle superior migration of the tumour. Operative
      difficulties were encountered during the dissection of the tumour from the neural
      structures in these cases. We conclude that with the availability of modern
      decongestive measures and basal surgical exposures, preoperative shunting is
      rarely indicated and can be occasionally dangerous. In the absence of actual
      proof, it is postulated that the secondary ventricular enlargement appears to be
      a protective mechanism of the brain helping to reduce tumour pressure on the
      basal forebrain structures.

PMID- 7632366
TI  - CT-guided stereotactic antero-medial pulvinotomy and centromedian-parafascicular
      thalamotomy for intractable malignant pain.
AB  - A quick and safe CT image-guided stereotactic thalamotomy technique that has
      proved ideal for alleviating medically refractory intractable pain due to
      malignant disease is described. A simple method of deriving cartesian coordinates
      for target points that facilitates functional neurosurgery using CT images and
      the Brown-Roberts-Wells stereotactic system is also described.

PMID- 7632367
TI  - "I've torn it: how to repair it".

PMID- 7632368
TI  - Tuberculoma of the cavernous sinus--a case report.
AB  - Although tuberculosis among Asian immigrants in Britain is not uncommon,
      intracranial tuberculomas are rare. An unusual case of a tuberculoma located in
      the left cavernous sinus is reported.

PMID- 7632369
TI  - Extrusion of peritoneal catheter of ventriculoperitoneal shunt through the
      urethra.

PMID- 7632370
TI  - Intracranial metastases from pituitary adenoma.
AB  - Two patients with histologically benign pituitary adenomas subsequently underwent
      resections of a frontal and a cerebellar tumour each of which had histological
      appearances identical to those of classic pituitary adenomas. The frontal tumour
      was immunoreactive for prolactin, and the cerebellar metastasis was
      immunoreactive for thyrotropin and gonadotrophins. There was no evidence of
      residual or recurrent intrasellar pituitary adenoma, nor was there a connection
      between the frontal or cerebellar masses and the sella turcica. Extracranial
      tumours have not developed. Both tumours fulfil criteria for diagnosis of
      pituitary carcinoma. These rare tumours are reviewed with emphasis on diagnosis
      and management.

PMID- 7632372
TI  - Stroke-induced cardiovascular changes: a rare cause of death from polyarteritis
      nodosa.
AB  - Polyarteritis nodosa (PAN) is an uncommon but well documented cause of
      subarachnoid haemorrhage (SAH). We report a case of SAH in a patient with PAN
      causing death indirectly from the effects of resultant cardiovascular changes
      upon other manifestations of PAN. Clinicians should be aware of the systemic
      effects of SAH in patients with known vasculitides.

PMID- 7632371
TI  - Spontaneous haemorrhage in acoustic neurinomas.
AB  - Gross intratumoural haemorrhage in acoustic neurinoma is rare. The authors
      describe seven patients, out of a consecutive 99 cases of acoustic neurinoma
      operated by the first author, who presented with haemorrhage. Risk factors for
      haemorrhage appear to be large size, mixed Antoni type and secondary vascular
      changes.

PMID- 7632373
TI  - The effect of radicular arteries ligation on the spinal cord blood supply in
      cats.
AB  - In order to study the contribution of the radicular arteries to the blood supply
      of the spinal cord, we performed experimental occlusion of these arteries in
      cats. In 43 cats, under thiopental anaesthesia, unilateral, bilateral, single or
      multiple ligations of dorsal radicular arteries were carried out. The animals
      were killed at the 1st, 2nd and 7th postoperative day. The spinal cords were
      removed and preserved in formalin solution for 1 month and then examined, using
      light microscopy. We conclude that bilateral or multiple ligations are capable of
      producing ischaemic lesions in the spinal cord, more profound by the seventh
      postoperative day, while single ligations do not produce such lesions, unless a
      medullary artery is involved. The ischaemic lesions which were observed were
      associated with clinical neurological deficits.

PMID- 7632374
TI  - Juvenile xanthogranuloma of nerve root origin.
AB  - A case of juvenile xanthogranuloma arising from the first sacral nerve root is
      reported together with a review of the literature. The patient presented with
      symptoms of low back pain and sciatica, and with S1 nerve root tensions signs.
      Computed tomography and magnetic resonance imaging revealed a mass arising from
      the right S1 nerve root. The tumour was resected, and the morphological and
      immunocytochemical appearances of the lesion confirmed the diagnosis of juvenile
      xanthogranuloma. Soft tissue juvenile xanthogranulomas have been described but
      are extremely rare. However, we believe this is the first reported case of such a
      tumour affecting a spinal nerve root.

PMID- 7632375
TI  - Comment on Page & Miles' "Validation of CT targeting for functional stereotaxis
      with postoperative magnetic resonance imaging".

PMID- 7632376
TI  - A modified frontal approach for anterior circle of Willis aneurysms.

PMID- 7632377
TI  - Comment on "A modified frontal approach for anterior circle of Willis aneurysm".

PMID- 7632378
TI  - Re: Glasgow Outcome Scale in assessments of subarachnoid haemorrhage results.

PMID- 7632379
TI  - Hexamethylenetetramine: extinction and thermal vibrations from neutron
      diffraction at six temperatures.
AB  - Neutron diffraction data have been collected for hexamethylenetetramine (HMT) at
      15, 50, 80, 120, 160 and 200K using a single crystal (mass 8.1 mg). The structure
      refinement at each temperature included two extinction parameters and third-order
      thermal parameters for the H nuclei. Extinction effects are very severe with
      extinction factors as small as 0.2Fkin2 for three reflections (800, 110 and 440).
      Application of the Sabine extinction theory indicates that the crystal domain
      size decreases from 115 microns at 200 K to 85 microns at 15 K. The half-width in
      the mosaic spread (7" of arc) is almost independent of temperature. An extinction
      model without phase correlations between mosaic blocks gives a slightly better
      fit to the diffraction data. The nuclear mean square thermal displacements have
      been analysed assuming no coupling between the external (rigid body) and internal
      vibrations. This gives mean square displacements for rigid-body vibration in
      which zero-point vibrational effects are apparent. The methylene H nuclei have
      internal vibrations approximately independent of temperature. At 200 K, the H
      nuclear vibrations have a small anharmonic component, but at temperatures below
      160 K this becomes insignificant in terms of the experimental error.

PMID- 7632381
TI  - Efficient methods for the linearization and solution of phase-invariant
      equations.
AB  - This paper describes a linear least-squares procedure, whereby, through
      quadrupole relationships, the 2 pi integers that linearize sets of unique phase
      invariant estimates can be determined. It is subsequently shown that the phase
      solutions for these linear equations can be obtained, even for basis sets of
      thousands of phases, without having to either build or invert the full least
      squares matrix. The final r.m.s. phase errors achieved by this method can
      typically be less that 5 or 10 degrees.

PMID- 7632380
TI  - TDSIR phasing: direct use of phase-invariant distributions in macromolecular
      crystallography.
AB  - A new strategy for employing three phase triples invariant estimates from
      Hauptman's single isomorphous replacement (SIR) and anomalous dispersion (SAS)
      joint probability distribution formulae is outlined which produces a single
      unique phase-invariant solution in the case where the positions of the heavy-atom
      scatterers is known. A similar but non-identical result is obtained for the phase
      invariants of a structure for which a molecular-replacement solution has been
      obtained. It is important to note that the values of the individual
      native/derivative phases can be determined directly from the probability
      distribution formulae without having to utilize the phase-invariant estimates in
      an active way. Elimination of the multisolution aspect of utilizing phase
      invariant estimates should have important repercussions with regard to phasing
      macromolecular sets of derivatized data. Trial calculations based on
      experimentally measured 2.5 A data for three derivatives of cytochrome c550 are
      encouraging. The average of the three SIR maps resolves a number of structural
      ambiguities seen in the published multiple isomorphous replacement (MIR) map
      obtained from eight derivatives.

PMID- 7632382
TI  - Factors influencing the specialty choice of the physical medicine and
      rehabilitation graduating class of 1994 and the entering class of 1995.
AB  - To understand better how career choices are made by physiatrists, a 16-item, 7
      page questionnaire was sent to all 1994 graduating physical medicine and
      rehabilitation (PM&R) resident physicians in the United States. Of the 343 senior
      residents, 202 completed the questionnaire for a response rate of 59%. The
      questionnaire focused on the following areas: timing of the decision to enter
      PM&R; and how the medical school curriculum, certain groups of people, and
      certain specific factors influenced their choices. There were 130 factors modeled
      after the American Association of Medical Colleges (AAMC) annual medical student
      questionnaire that the recipients were asked to grade on a numerical scale: 1 =
      unimportant to 5 = very important. Of the graduating residents, 60.1% (119/198)
      made the decision to enter PM&R in their 3rd or 4th yr of medical school, 13.1%
      (26/198) in the first 2 yr, and 11.1% (22/198) after starting another residency.
      The five factors ranked most important in the decision were (mean rank score):
      sufficient time/flexibility for family obligations (4.60); opportunity to make a
      difference in peoples lives (4.57); interest in helping people (4.55); types of
      patient problems encountered (4.50); and consistency with personality (4.49). We
      also obtained the AAMC's 1993 annual data on medical students choosing PM&R.
      Their top five factors were the same as those listed by the graduating residents,
      but in a slightly different rank order. Profiles have also been derived on those
      graduating PM&R residents who chose an academic career (n = 68) v nonacademic (n
      = 133) and fellowship (n = 34) v nonfellowship (n = 163).

PMID- 7632383
TI  - Curriculum needs in physical medicine and rehabilitation for primary care
      physicians. Results of a survey.
AB  - A 45-item survey assessing the need for knowledge and skills in clinical problems
      commonly encountered in physical medicine and rehabilitation was sent to 300
      randomly selected family practitioners in the state of Indiana. The purpose of
      this survey was to determine the clinical needs self-perception of these
      physicians to help design a physical medicine and rehabilitation curriculum that
      would be the most relevant to medical students in light of today's emphasis on
      primary care. Another purpose of the study was to compare the responses with
      those of a similar survey done among Ohio general practitioners in 1974. The
      family physicians gave the highest scores in terms of overall need to those items
      most frequently encountered in practice, especially musculoskeletal problems.
      They tended to rank much lower those clinical problems that they typically refer
      to other specialists for care. This survey and the one in 1974 showed remarkably
      similar results. Only a few items showed considerable change in their overall
      rank or need. Carpal tunnel syndrome and prescription of wheelchairs, canes, and
      assistive devices both rose in importance in this survey. Items that were ranked
      lower in importance on this survey than in 1974 included juvenile rheumatoid
      arthritis; the use of modalities, such as ultrasound, diathermy, and paraffin;
      cardiac rehabilitation; stroke rehabilitation; and chronic lung rehabilitation.
      Although this self-assessment tool provides pertinent and very useful information
      regarding curricular needs, it cannot be the only source of information in this
      regard.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7632384
TI  - Assessing handicap of stroke survivors. A validation study of the Craig Handicap
      Assessment and Reporting Technique.
AB  - Proxy agreement and internal structure of the Craig Handicap Assessment and
      Reporting Technique are documented, and the measure is compared with the
      Functional Independence Measure for a sample of stroke survivors. Thirty-eight
      former rehabilitation patients were assessed at follow-up (average time post
      stroke was 6 mo) with the Craig Handicap Assessment, which was also answered
      separately under proxy instructions by caregivers (relatives or friends) who
      accompanied patients to the interview. Proxy instructions were for caregivers to
      answer as if they were the stroke survivor. Proxy agreement for the Craig
      Handicap total score was good (intraclass correlation was 0.77) and adequate for
      most of its scales. The physical independence, mobility, and occupation scales
      were highly intercorrelated, with low intercorrelations for social integration
      and economic self-sufficiency. Correlation between the handicap and Functional
      Independence Measure disability scores was around 0.50; when the handicap
      economic self-sufficiency scale was removed, this increased to 0.70. These
      findings are discussed within the context of the interrelationships among the
      educational level of the patients and both measures. With some modification, the
      Craig Handicap Assessment and Reporting Technique appears to be a useful tool for
      assessing outcomes in terms of the handicap status of stroke survivors.

PMID- 7632385
TI  - Outcomes and problems in pediatric pulmonary rehabilitation.
AB  - OBJECTIVE: To provide baseline information on the state of pediatric pulmonary
      rehabilitation, including data regarding diagnosis, age, gender, race,
      gestational age, disposition, medications, complications, procedures,
      consultations, pulmonary status, and outcomes. DESIGN: Retrospective review.
      SETTING: Pediatric pulmonary rehabilitation unit of a pediatric rehabilitation
      hospital that is free-standing, but that receives most of its referrals from a
      tertiary care pediatric hospital. PATIENTS: All patients (70 subjects) who had
      completed a course of inpatient rehabilitation over the 5-yr life of the
      hospital. MAIN OUTCOME MEASURES: Descriptive data were collected in regard to the
      objectives. In addition, outcome measures were developed for this study. They
      include measurements of developmental equivalence at admission and discharge and
      the changes in these scores, both actual and expected. RESULTS: Descriptive
      characteristics are listed in the text. Forty-six patients had bronchopulmonary
      dysplasia (BPD). The success rate of weaning those with BPD who were admitted
      with a goal of ventilator weaning was 81% (24% for those without BPD). On
      admission, 36 of those with BPD required three pulmonary aids (O2, continuous
      positive airway pressure, ventilator, and tracheostomy); at discharge, 28
      required three aids. Of those without BPD, 16 required three aids at admission
      and 14 did so at discharge. CONCLUSIONS: Basic descriptive data are provided. The
      characteristics are similar to those in previous studies, although with a larger
      sample size and more detail. The outcome measures described cannot be compared
      with a criterion standard, but do offer a starting point in this underdeveloped
      field and will assist in future research directions.

PMID- 7632386
TI  - Predicting discharge outcome after elective hip and knee arthroplasty.
AB  - The objective of this prospective study was to determine if differences exist
      between individuals who require an inpatient rehabilitation program after
      elective hip and knee arthroplasty from those patients who can be discharged
      directly home. Multiple variables consisting of baseline demographics, social
      status, insurance status, medical history, pain level, quantitative strength,
      range of motion, and functional ability were examined. The primary outcome
      measure was the discharge destination from the orthopedic service and consisted
      of either a discharge to home or a discharge to an inpatient rehabilitation unit.
      Of the 162 patients followed, 65 (40%) were discharged to an inpatient
      rehabilitation unit, whereas 97 were discharged to home. The patients discharged
      to inpatient rehabilitation tended to live alone, were significantly older (mean
      difference = 6.3 yr), and had increased comorbid conditions (p < 0.001 for all
      variables). Patients discharged to a rehabilitation unit reported significantly
      greater pain levels than those discharged to home (P < 0.001). The attainment of
      a supervision level of function demonstrated greater differences between groups
      than the attainment of independent function for all functional measures. A
      logistic regression model was developed that predicted 76% of the discharges to
      rehabilitation by the third physical therapy session postsurgery. In conclusion,
      predictive markers do exist that differentiate individuals who require further
      inpatient therapy services after joint replacement surgery.

PMID- 7632387
TI  - Kinesiology of the empty can test.
AB  - The "empty can test" has been described to isolate supraspinatus muscle activity
      from the activity of other rotator cuff muscles. The shoulder is positioned in 90
      degrees of abduction, with full internal rotation, and 30 degrees of forward
      flexion and maintained against resistance. The purpose of this study was to
      determine if the supraspinatus muscle is isolated by the empty can test. Ten
      normal male subjects were studied (age 25-43/mean 32) with fine-wire
      electromyography recording from their nondominant arm middle deltoid,
      supraspinatus, infraspinatus, and teres minor. During the maneuver electromyogram
      activity was seen not only in the supraspinatus, but also in the infraspinatus
      and the middle head of the deltoid. Teres minor was inactive throughout the test;
      however, this is interesting because the teres minor and infraspinatus have
      previously been described as a functional unit. Our study found that the empty
      can test does not allow selective activation of the supraspinatus muscle.

PMID- 7632388
TI  - Medial femoral cutaneous nerve conduction.
AB  - Medial femoral cutaneous nerve (MFCN), a sensory branch of the femoral nerve,
      supplies the skin on the anterior medial aspect of the thigh and knee. A
      conduction study for this nerve is described. A recording electrode was placed
      anterior-medially in the thigh and 14 cm distal to the stimulating cathode that
      was placed immediately lateral to the femoral artery just below the inguinal
      ligament. Sixty-four nerves of 32 adults with a mean age of 40 yr (range, 21-56)
      were tested. The latencies to the onset and peak were 2.4 +/- 0.2 and 2.9 +/- 0.2
      ms, respectively. The amplitude of baseline to negative peak was 4.9 +/- 1.0
      microV. The conduction velocity calculated by the distance divided by the onset
      latency was 60 +/- 5 m/s. We conclude that the MFCN is accessible for
      electrophysiologic evaluation, which may help in diagnosing the MFCN or femoral
      neuropathy.

PMID- 7632390
TI  - Vision rehabilitation: an overlooked subject in physiatric training and practice.
      Commentary.

PMID- 7632389
TI  - Wheelchair safety--adverse reports to the United States Food and Drug
      Administration.
AB  - Evidence has been accumulating that injuries related to wheelchair use are common
      and sometimes serious. The object of this study was to evaluate the databases of
      the Food and Drug Administration (FDA) for insights to the nature and causes of
      such problems. We analyzed 651 records that were received by the FDA between 1975
      and 1993. There were 368 injuries, 21 of which were fatal, affecting 334
      wheelchair users. Fractures were the most common (45.5%), with lacerations
      (22.3%) and contusions/abrasions (20.1%) accounting for most of the remainder.
      The proportion of incidents related to the use of scooters, powered wheelchairs,
      and manual wheelchairs were 52.8%, 24.6%, and 22.6%, respectively. Four broad
      classes of contributing factors, often acting in combination, were implicated:
      engineering (60.5%), environmental (25.4%), occupant (9.6%), and system (4.6%).
      Of the tips and falls, those in the forward direction were most common in
      incidents affecting manual or powered wheelchairs, but the sideways direction was
      most common in scooters. The FDA database provides a unique perspective on
      wheelchair safety, with implications for clinicians, users, manufacturers, and
      regulatory bodies.

PMID- 7632391
TI  - Functional status and therapeutic intensity during inpatient rehabilitation.
AB  - The objective of this study was to describe the relationships between functional
      status at discharge and intensity of therapies received during inpatient medical
      rehabilitation. The sample was comprised of 140 patients with traumatic brain
      injury and 106 patients with spinal cord injury at eight hospitals that subscribe
      to the Uniform Data System for Medical Rehabilitation. Data included linear
      measures of motor and cognitive ability derived from the Functional Independence
      Measure at admission to and discharge from rehabilitation. Multiple regression
      was used to predict intensity of therapies, discharge motor and cognitive
      function, the extent to which potential functional gains were achieved, and the
      efficiency of gains. Intensities of occupational, physical, and speech therapies
      were not significant predictors of outcomes for either group, controlling
      linearly for admission function, psychology intensity, length of stay, onset to
      admission interval, age, and interrupted stays. Only intensity of psychology
      services seemed to have any relation to functional gain (in cognition for
      patients with traumatic brain injury). The apparent lack of benefit related to
      intensity of therapies may be due to factors such as spontaneous recovery, goals
      not measured by the Functional Independence Measure, limited modulation of
      therapy intensity according to likely patient responsiveness, or therapies
      focused on impairment or other goals rather than disability. We suggest that
      efficiently staged rehabilitation should vary the intensity and nature of
      services according to patients' functional status, impairments, comorbid
      conditions, and other clinical factors.

PMID- 7632392
TI  - Construction and heterologous expression of a synthetic copy of the cutinase cDNA
      from Fusarium solani pisi.
AB  - A copy of the cutinase cDNA from Fusarium solani pisi was constructed starting
      from synthetic oligonucleotides. For this construction three separate cassettes
      were made, which were subsequently assembled to form the cutinase gene.
      Heterologous expression of the synthetic cutinase gene and the subsequent
      secretion of the recombinant enzyme was achieved in Saccharomyces cerevisiae and
      Aspergillus awamori.

PMID- 7632393
TI  - The effect of various introns and transcription terminators on the efficiency of
      expression vectors in various cultured cell lines and in the mammary gland of
      transgenic mice.
AB  - Various combinations of promoters, introns and transcription terminators were
      used to drive the expression of bovine growth hormone (bGH) cDNA in different
      cell types. In constructs containing the human cytomegalovirus (hCMV) promoter
      and the SV40 late genes terminator, the intron from SV40 genes (VP1) was much
      more efficient, than the intron from the early genes (t). The synthetic intron
      SIS generated by the association of an adenovirus splice donor and an
      immunoglobulin G splice acceptor showed the highest activity. The respective
      potency of these introns was similar in several mammalian (CHO, HC11 and COS) and
      fish (TO2 and EPC) cells. The rabbit whey acidic protein (WAP) gene promoter was
      highly efficient to drive the expression of bGH gene in the HC11 mammary cell
      lines. In contrast, the bGH cDNA under the control of the same promoter was much
      less efficiently expressed when the SV40 VP1 intron and transcription terminator
      were used. The rabbit WAP gene and the human GH gene terminators did not or only
      moderately enhanced the expression of the construct WAP bGH cDNA. Introduction of
      a promoter sequence from the mouse mammary tumor virus (MMTV) LTR in the VP1
      intron increased very significantly the expression of the WAP bGH cDNA. Although
      several of these vectors showed high potency when expressed stably in HC11 cells,
      all of them were only moderately efficient in transgenic mice. These data
      indicate that the VP1 and the SIS introns may be used to express foreign cDNAs
      with good efficiency in different cell types. The addition of an enhancer within
      an intron may still reinforce its efficiency. However, transfection experiments,
      even when stable expression is carried out, are poorly predictive of the
      potential efficiency of a vector in transgenic animals.

PMID- 7632394
TI  - Novel bioemulsifiers from microorganisms for use in foods.
AB  - The main objective of this study was to test the range of microorganisms for
      production of extracellular, high molecular weight emulsifiers for potential use
      in foods. A standard emulsification assay developed specifically for assessing
      food emulsifiers was used to examine 24 extracellular microbial products from
      bacteria, yeasts and algae. Of the 24 products tested, nine had emulsification
      ability that was as good as and eight had emulsifying properties that were better
      than those of the commonly used food emulsifiers gum arabic and
      carboxymethylcellulose. The eight good producer organisms included the yeasts
      Candida utilis, Candida valida, Hansenula anomala, Rhodospiridium diobovatum and
      Rhodotorula graminis, the red alga Porphiridium cruentum, and the bacteria
      Klebsiella spp. and Acinetobacter calcoaceticus. Of these, C. utilis was selected
      for further study due to the excellent emulsification properties of its
      extracellular products and food-grade status of the organism. Crude preparations
      of the bioemulsifier from C. utilis exhibited low viscosity and had a
      carbohydrate content of over 80%. Preliminary trials showed that the
      bioemulsifier from this organism had potential for use in salad cream.

PMID- 7632395
TI  - Safe biotechnology. Part 6. Safety assessment, in respect of human health, of
      microorganisms used in biotechnology.
AB  - The assessment of microorganisms in respect to human health is an important step
      for the introduction of new natural and genetically modified production strains
      to biotechnology. This report outlines the potential hazards posed by industrial
      microorganisms, important considerations related to pathogenicity, such as routes
      and portals of entry into the human body, mechanisms of spread of biological
      material and a definition of pathogenicity. Furthermore the most important steps
      in the assessment of pathogenicity of unknown strains are described. A short
      overview on characterization and in vitro and in vivo tests is presented. The
      hazard related to allergens and toxic metabolites is reviewed and the choice of
      methods and the handling of strains with unknown potential are discussed.

PMID- 7632396
TI  - Efficient production of anti-(hepatitis B virus) antibodies and their
      neutralizing activity in chimpanzees.
AB  - For industrial production of human monoclonal antibodies (hmAb) against hepatitis
      B virus surface antigen (HBsAg), we scaled-up a short-term perfusion culture in
      serum-free medium, which was chosen as the most suitable culture method, to a 50
      1 fermentor equipped with a rotating shear filter. Using hydrophobic
      chromatography as the initial step of hmAb purification, the mAb HBW4, HBW6 and
      W471 were isolated in good quality from the respective culture broths in yields
      of approximately 75%. Each of the three purified hmAb alone, and a cocktail of
      the three, protected chimpanzees against HB virus, when injected intravenously 3
      h after viral challenge, as long as the serum antibody levels were significant. A
      pharmacokinetic study using cynomolgus monkeys demonstrated that the hmAb have a
      long plasma half-life and bioavailability of approximately 76% upon intramuscular
      injection in primates. Thus, anti-HBsAg hmAb produced by an industrial process
      are expected to be successfully used in clinical fields.

PMID- 7632397
TI  - Purification and properties of an alkaline protease from alkalophilic Bacillus
      sp. KSM-K16.
AB  - Alkaline protease (EC 3.4.21.14) activity, suitable for use in detergents, was
      detected in the alkaline culture medium of Bacillus sp. KSM-K16, which was
      originally isolated from soil. The enzyme, designated M protease, was purified to
      homogeneity from the culture broth by column chromatographies. The N-terminal
      amino acid sequence was Ala-Gln-Ser-Val-Pro-Trp-Gly-Ile-Ser-Arg- Val-Gln-Ala-Pro
      Ala-Ala-His-Asn-Arg-Gly-Leu-Thr-Gly. The molecular mass of the protease was 28
      kDa, and its isoelectric point was close to pH 10.6. Maximum activity toward
      casein was observed at 55 degrees C and at pH 12.3 in 50 mM phosphate/NaOH
      buffer. The activity was inhibited by phenylmethylsulfonyl fluoride and
      chymostatin. The enzyme was very stable in long-term incubation with liquid
      detergents at 40 degrees C. The enzyme cleaved the oxidized insulin B chain
      initially at Leu15-Tyr16 and efficiently at ten more sites. Among various
      oligopeptidyl p-nitro-anilides (pNA) tested, N-succinyl-Ala-Ala-Pro-Phe-pNA was
      efficiently hydrolyzed by M protease. M protease was precipitated in (NH4)2SO4
      saturated acetate buffer (pH 5.0) as plank-like crystals.

PMID- 7632398
TI  - Production of isoleucine by overexpression of ilvA in a Corynebacterium
      lactofermentum threonine producer.
AB  - Overproduction of isoleucine, an essential amino acid, was achieved by
      amplification of the gene encoding threonine dehydratase, the first enzyme in the
      threonine to isoleucine pathway, in a Corynebacterium lactofermentum threonine
      producer. Threonine overproduction was previously achieved with C. lactofermentum
      ATCC 21799, a lysine-hyperproducing strain, by introduction of plasmid pGC42
      containing the Corynebacterium homdr and thrB genes (encoding homoserine
      dehydrogenase and homoserine kinase respectively) under separate promoters. The
      pGC42 derivative, pGC77, also contains ilvA, which encodes threonine dehydratase.
      In a shake-flask fermentation, strain 21799(pGC77) produced 15 g/l isoleucine,
      along with small amounts of lysine and glycine. A molar carbon balance indicates
      that most of the carbon previously converted to threonine, lysine, glycine and
      isolecine was incorporated into isoleucine by the new strain. Thus, in our
      system, simple overexpression of wild-type ilvA sufficed to overcome the effects
      of feedback inhibition of threonine dehydratase by the end-product, isoleucine.

PMID- 7632399
TI  - A novel promoter, derived from the isocitrate lyase gene of Candida tropicalis,
      inducible with acetate in Saccharomyces cerevisiae.
AB  - When the isocitrate lyase gene, containing 5'-upstream and 3'-flanking regions,
      of an n-alkane-assimilating yeast Candida tropicalis was introduced into
      Saccharomyces cerevisiae, the enzyme was functionally overexpressed in the cells
      grown on acetate. The amount of the recombinant isocitrate lyase expressed in S.
      cerevisiae was as much as 30% of the total soluble proteins in the cells, being
      comparable to that with GAL7 functional under the control of galactose. The
      expression was also observed when the cells were grown on glycerol, lactate,
      ethanol or oleate. These facts indicate that the isocitrate lyase gene upstream
      region (UPR-ICL) contains a strong promoter functional in S. cerevisiae. UPR-ICL
      is active as a promoter on cheap carbon sources such as acetate and
      nonconventional carbon sources such as oleate, whereas many conventional strong
      promoters demand relatively expensive sugars or sugar derivatives. Therefore, it
      is promising to construct an economical recombinant protein production system by
      using UPR-ICL.

PMID- 7632400
TI  - A target-specific chimeric toxin composed of epidermal growth factor and
      Pseudomonas exotoxin A with a deletion in its toxin-binding domain.
AB  - We have fused the epidermal growth factor (EGF) to the amino terminus of
      Pseudomonas exotoxin A (PE) to create a cytotoxic agent, designated EGF-PE, which
      preferentially kills EGF-receptor-bearing cells. In this study, we analyzed the
      effect of the Ia domain, the binding domain of PE on the cytotoxicity of EGF-PE
      towards EGF-receptor-bearing cells and tried to develop a more potent EGF
      receptor-targeting toxin. EGF-PE molecules with sequential deletions at the amino
      terminus of PE were constructed and expressed in E. coli strain BL21(DE3). The
      cytotoxicity of these chimeric toxins was then examined. Our results show that
      the amino-terminal and carboxy-terminal regions of the Ia domain of PE are
      important for the cytotoxicity of a PE-based targeting toxin. To design a more
      potent PE-based EGF-receptor-targeting toxin, a chimeric toxin, named EGF
      PE(delta 34-220), which had most of the Ia domain deleted but retained amino acid
      residues 1-33 and 221-252 of this domain, was constructed. EGF-PE(delta 34-220)
      has EGF-receptor-binding activity but does not show PE-receptor-binding activity
      and is mildly cytotoxic to EGF-receptor-deficient NR6 cells. As expected, EGF
      PE(delta 34-220) is a more potent cytotoxic agent towards EGF-receptor-bearing
      cells than EGF-PE(delta 1-252), where the entire Ia domain of PE was deleted. In
      addition, EGF-PE(delta 34-220) was shown to be extremely cytotoxic to EGF
      receptor-bearing cancer cells, such as A431, CE81T/VGH, and KB-3-1 cells. We also
      found that EGF-PE(delta 34-220) was highly expressed in BL21(DE3) and could be
      easily purified by urea extraction. Thus, EGF-PE(delta 34-220) can be a useful
      cytotoxic agent towards EGF-receptor-bearing cells.

PMID- 7632401
TI  - Screening and characterization of microorganisms with glutaryl-7ADCA acylase
      activity.
AB  - A screening of microorganisms producing glutaryl-7ADCA acylase, an enzyme able to
      hydrolyse glutaric acid selectively from glutaryl-3-deacetoxy-7
      aminocephalosporanic acid (glutaryl-7ADCA), has been carried out in soil samples.
      Five microorganisms expressing acylase activity were isolated and classified as
      Bacillus cereus, Achromobacter xylosooxidans, Bacillus sp., Pseudomonas sp. and
      Pseudomonas paucimobilis. The screening was carried out by preparing enrichment
      cultures containing glutaryl-7-ADCA or cephalosporin C as the selective carbon
      source. Four model compounds (adipoyl-, glutamyl- and glutaryl-p-nitroanilide and
      glutarylcoumarin), mimicking the glutaryl-7ADCA beta-lactam moiety, were
      synthesized as substrates suitable for the rapid screening of the microorganisms
      (2500) isolated from the enrichment cultures. A total of 300 strains were active
      on the model substrates and only 5 displayed acylase activity on glutaryl-7ADCA.
      The fermentation parameters, such as pH and inducer concentration, for the
      optimal acylase expression and acylase specificity towards the model substrates
      were different for each strain.

PMID- 7632403
TI  - Use of surfactants and slurrying to enhance the biodegradation in soil of
      compounds initially dissolved in nonaqueous-phase liquids.
AB  - A study was conducted to find means of enhancing the biodegradation of
      hydrophobic organic compounds in nonaqueous-phase liquids (NAPLs). The effects of
      surfactants, identity of the NAPL and agitation was investigated. When present in
      NAPLs, phenanthrene, di-(2-ethylhexyl) phthalate (DEHP) and biphenyl were
      mineralized slowly in soil. Addition of Triton X-100 or Alfonic 810-60 did not
      enhance the degradation of phenanthrene initially in hexadecane or dibutyl
      phthalate. Slurrying the soil increased the rate and extent of mineralization of
      phenanthrene initially in hexadecane but not in dibutyl phthalate. Addition of
      either of the two surfactants to the slurries did not promote the transformation.
      Triton X-100, Alfonic 810-60 and Tergitol 15-S-9 below their critical micelle
      concentrations increased the rate and sometimes the extent of mineralization in
      soil slurries of phenanthrene initially in 2,2,4,4,6,8,8-heptamethylnonane, but
      other surfactants were not stimulatory. Slurrying the soil promoted the initial
      mineralization of DEHP initially in dibutyl phthalate, and Alfonic 810-60 and
      Triton X-100 further stimulated the rate and extent of degradation in the
      slurries. Alfonic 810-60 increased the extent of mineralization in slurries of
      biphenyl in hexadecane but not in dibutyl phthalate, cyclohexane, kerosene or two
      oils. Little mineralization of biphenyl or DEHP initially in dibutyl phthalate
      occurred in soil slurries, but Tween 80, Tergitol 15-S-40 and Tergitol 15-S-9
      increased the extent of mineralization. However, vigorous agitation of the
      slurries of soil acclimated to DEHP or the use of small volumes of the NAPL
      resulted in marked enhancement of the degradation.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7632402
TI  - Glyphosate-degrading isolates from environmental samples: occurrence and pathways
      of degradation.
AB  - The metabolism of the organophosphonate herbicide glyphosate was investigated in
      163 environmental bacterial strains, obtained by a variety of isolation
      strategies from sites with or without prior exposure to the compound. Isolates
      able to use glyphosate as sole phosphorus source were more common at a treated
      site, but much less abundant than those capable of using the glyphosate
      metabolite aminomethylphosphonic acid (AMPA). Nevertheless, all 26 strains found
      to metabolise the herbicide did so via an initial cleavage of its carbon
      phosphorus bond to yield sarcosine; no evidence for its metabolism or co
      metabolism to AMPA was obtained.

PMID- 7632404
TI  - Studies on the capacity of the cellulase of the anaerobic rumen fungus Piromonas
      communis P to degrade hydrogen bond-ordered cellulose.
AB  - The anaerobic rumen fungus Piromonas communis, when cultured on cotton fibre as
      the carbon source, produces an extracellular cellulase that is capable of
      solubilizing "crystalline" hydrogen-bond-ordered cellulose, in the form of the
      cotton fibre, at a rate that is greater than that of any other cellulases
      reported in the literature hitherto. The cell-free culture fluid is also very
      rich in xylan-degrading enzymes. The activity towards crystalline cellulose
      resides in a high-molecular-mass (approximately 700-1000 kDa) component (so
      called crystalline-cellulose-solubilizing component, CCSC) that comprises endo (1
      ->4)-beta-D-glucanase (carboxymethylcellulase), beta-D-glucosidase and another
      enzyme that appears to be important for the breakdown of hydrogen-bond-ordered
      cellulose. The CCSC is associated with only a small amount of the endo(1-->4)
      beta-D-glucanase (1.9%), beta-D-glucosidase (0.7%) and protein (0.5%) found in
      the crude cell-free cellulase preparation. The CCSC, unlike the bulk of the
      endo(1-->4)-beta-D-glucanase and beta-D-glucosidase, is very strongly absorbed on
      the microcrystalline cellulose, Avicel.

PMID- 7632405
TI  - Cholesterol concentrations and depression in elderly people.

PMID- 7632406
TI  - Depression and suicide.

PMID- 7632407
TI  - Postmenopausal hormone-replacement therapy and cardiovascular risk.
AB  - Case-control and cohort studies support the hypothesis that postmenopausal
      oestrogen-replacement therapy reduces the risk of atherosclerotic disease
      manifestations. The evidence for a cardioprotective effect of such a therapy is,
      however, incomplete because randomized prospective studies are missing. Because
      it may be almost impossible to conduct placebo-controlled trials in the future,
      other study designs will be needed to minimize selection bias. Further work is
      required to define the optimal dose and administration schedule of oestrogen and
      to determine whether addition of progestogens alters the beneficial effect of
      oestrogen on the cardiovascular system. Such studies may also provide mechanistic
      insight into the interaction between lipoprotein metabolism and haemostasis and
      its relation to the atherosclerotic disease process.

PMID- 7632408
TI  - The genetic basis of resistance to cancer chemotherapy.
AB  - The Goldie-Coldman hypothesis of how tumours develop resistance to chemotherapy
      predicts that random mutations occur within a tumour cell population that bestows
      cytotoxic resistance. These resistance mechanisms may be specific to a certain
      class of cytotoxic drug, such as changes the enzymes topoisomerase II and
      dihydrofolate reductase, or may affect many drugs simultaneously, such as
      increased expression of P-glycoprotein. Knowledge of the genetic basis of these
      resistance mechanisms will have fundamental clinical importance in individual
      cases by allowing cytotoxic regimes that are unaffected to be chosen. Moreover,
      it will allow the development of more effective modulators of resistance.

PMID- 7632409
TI  - The autoimmune basis of dilated cardiomyopathy.
AB  - Dilated cardiomyopathy is a form of heart disease characterized by ventricular
      dilatation and reduced systolic function. In most patients, dilated
      cardiomyopathy is a sporadic disease. However, 20% of dilated cardiomyopathy
      patients may have a familial form of the disease. The aetiologies of both the
      sporadic and familial forms of dilated cardiomyopathy are unknown in most cases.
      Dilated cardiomyopathy has a spectrum of clinical and subclinical presentations.
      During the last 10 years, there have been many investigations concerning the
      possible aetiologic role of immune factors in dilated cardiomyopathy. It is
      plausible that an antecedent viral infection initiates an immunological cascade
      which in turn leads to production of autoimmune antibodies resulting in dilated
      cardiomyopathy. However, in most dilated cardiomyopathy patients, an antecedent
      viral infection cannot be identified. Similarly, the trail of immunological
      research has diverged as different groups have identified distinct autoantibodies
      or other immune factors in heterogeneous subsets of dilated cardiomyopathy and
      control patients. In this manuscript, we review the studies which have
      contributed supportive and confounding evidence to the theoretical autoimmune
      basis of dilated cardiomyopathy.

PMID- 7632410
TI  - Diagnosis and treatment of vulvodynia.
AB  - Vulvodynia is a complex multifactorial and multidisciplinary clinical syndrome of
      unexplained vulvar pain, sexual dysfunction, and psychological disability.
      Because of the absence of abnormal physical findings among such patients,
      vulvodynia was long thought to be solely a psychosomatic syndrome. The incidence
      or prevalence of vulvodynia has not been well studied. The recognition of
      specific subtypes of vulvodynia is important in the management of patients with
      vulvodynia. The most common subtypes are vulvar vestibulitis syndrome, cyclic
      vulvovaginitis and dysesthetic vulvodynia. Simple practice guidelines can be
      developed to facilitate the evaluation and management of such patients.
      Systematic epidemiological, etiological and therapeutic studies of vulvodynia are
      urgently needed.

PMID- 7632411
TI  - Genetic locus for psoriasis identified.

PMID- 7632412
TI  - Molecular genetics of venous thromboembolism.
AB  - Venous thrombosis is often familial, but until recently well-defined genetic
      defects were only found in a minority of patients. The situation changed with the
      discovery of inherited resistance to activated protein C (APC) as a novel
      mechanism for familial thrombophilia. It is caused by a single point mutation in
      the factor V gene, which predicts replacement of Arg506 in the APC-cleavage site
      with a Gln. APC resistance is found in a majority of patients with familial
      thrombosis as well as in 3-7% of the general population. It afflicts affected
      individuals with a life-long increased risk of thrombosis. The factor V gene
      mutation is the most prevalent single gene defect associated with thromboembolic
      disease so far described.

PMID- 7632413
TI  - Influence of oral contraceptive use on lipoprotein (a) and other coronary heart
      disease risk factors.
AB  - We have studied the influence of oral contraceptive use on lipoprotein (a) levels
      in a cohort of women aged 18, 21 and 24 years (n = 559). Data was available on
      oral contraceptive formulation and dosage, anthropometric variables, exercise,
      serum lipoprotein (a), insulin, lipid and apolipoprotein levels. Lipoprotein (a)
      was determined by radioimmunoassay. Differences were assessed with non-parametric
      statistical methods. Forty per cent of the study women used oral contraceptives.
      The use of desogestrel-containing monophasic preparations was associated with
      lower levels of lipoprotein (a) compared to triphasic/levonorgestrel formulations
      or to non-users (P = 0.005). This effect was seen only in non-smoking women. Oral
      contraceptive users had higher levels of serum apolipoprotein B, HDL3
      cholesterol, apolipoprotein A-I, triglycerides and systolic blood pressure, and
      lower serum lecithin:cholesterol acyltransferase activity. Lifestyle factors
      (smoking, exercise) showed no significant influence on lipoprotein levels. In
      conclusion, the use of desogestrel-containing oral contraceptives has a marked
      lowering effect on lipoprotein levels. Prospective studies will be needed to
      assess the net influence of oral contraceptive use on cardiovascular health.

PMID- 7632414
TI  - Two antireflux operations: floppy versus standard Nissen fundoplication.
AB  - The effects of fundic mobilization in Nissen fundoplication on belching ability,
      abdominal gas volume, bloating and flatus were assessed in a prospective,
      randomized study of 25 patients with refractory gastro-oesophageal reflux
      disease. Reflux was cured regardless of fundic mobilization. Subjective ability
      to belch was restored to preoperative in 73% of the patients with fundic
      mobilization, compared to 50% without. About 10% in both groups totally lost
      their ability to belch. Disturbance from flatus increased postoperatively
      slightly in both groups, but from bloating it remained the same or even
      diminished. The residual intra-abdominal radioactivity (median (interquartile
      range)) after provoked belching was preoperatively 8.9% (4.4-12.0) with and 13.2%
      (6.8-15.2) without fundic mobilization, compared to 36.7% (31.1-40.9) of the
      controls (P < 0.05). After fundoplication this residual activity was normalized
      in both study groups. Disturbance from postoperative bloating or flatus were not
      related to the ability of belching. Preoperatively symptomatic patients tended to
      have more complaints postoperatively. In conclusion, fundic mobilization restored
      belching ability slightly more effectively without compromising antireflux
      efficacy, but there did not seem to be any advantage regarding flatus or
      bloating.

PMID- 7632415
TI  - Modern trends in postoperative pain control. Symposium.

PMID- 7632416
TI  - Peripheral acute pain mechanisms.
AB  - Many studies in several species, including humans, have identified a subset of
      primary afferent nerve fibres that are activated by potential or actual tissue
      damaging stimuli. Discharge patterns of these nociceptive afferents faithfully
      reproduce some aspects of the applied stimuli (e.g. shape of the stimulus
      response function) but not others (e.g. time-course of a sustained stimulus).
      Since primary nociceptive afferents provide the input to the central nervous
      system, their encoding properties have to be considered when studying central
      processing. On the other hand, pain perception correlates with some aspects of
      nociceptor discharges (e.g. fatigue with repetition of brief heat pulses), but
      not with others (e.g. absolute thresholds). Therefore, the painfulness of a
      stimulus cannot be deduced from nociceptor discharges alone; central processing
      needs to be taken into account, particularly central summation. In addition to
      the immediate responses of nociceptive afferents to external stimulation, acute
      pain mechanisms also comprise the short-term plasticity of the nociceptive system
      as a consequence of prolonged noxious stimulation.

PMID- 7632417
TI  - Peripheral opioid receptors.
AB  - Recent experimental and clinical research has demonstrated that opioids can
      produce potent and receptor-specific analgesic effects outside the central
      nervous system. Opioid receptors are localized on peripheral terminals of sensory
      nerves and their endogenous ligands, opioid peptides, have been discovered in
      immune cells within inflamed tissue. Many controlled clinical studies confirm the
      experimental data. These findings open up the exciting perspective of the
      development of an entirely novel generation of peripherally active opioid
      analgesics devoid of centrally mediated side effects.

PMID- 7632418
TI  - Central acute pain mechanisms.
AB  - This account will consider the events occurring in the spinal cord that give rise
      to acute pain. The transmission and control of acute pain is not immutable but
      subject to plasticity so that the dividing line between acute and chronic pain is
      difficult to draw. Very brief acute pain is transmitted in a simple way and
      rarely produces difficulties in treatment. The situation within the spinal cord
      changes if the stimulus continues. After only seconds of C-fibre stimulation,
      additional peptides are released from C fibres, and spinal N-methyl-D-aspartate
      (NMDA) receptor activation and nitric oxide production occur. Soon after, genes
      are induced in central neurones, and increases and decreases in diverse
      pharmacological systems involved in pain transmission and modulation occur over
      periods of only a few hours. This rapid plasticity has important implications for
      the pharmacological treatment of acute because both the level of pain
      transmission and pain modulation will be altering over time.

PMID- 7632419
TI  - Intervention with spinal NMDA, adenosine, and NO systems for pain modulation.
AB  - Understanding of the complex pharmacology of the spinal cord may lead to rational
      advances in pain treatment. It appears that a number of specific neurochemical
      mechanisms exist, by which spinally administered receptor selective agents may
      modify nociceptive transmission. Spinal administration of pure competitive N
      methyl-D-aspartate (NMDA) antagonists affects only hyperpathic pain components,
      i.e. with signs of central sensitization, and most probably has a very limited
      role in postoperative pain treatment. On the other hand, it is well established
      that the non-competitive NMDA-antagonist ketamine gives good postoperative
      analgesia, probably by cerebral mechanisms also affecting other sensory
      modalities. Pure adenosine A1-receptor agonism at the spinal level mainly affects
      sensory allodynia to vibration, and is probably no alternative for postoperative
      pain treatment. In contrast, i.v. infusions of the non-selective A1/A2-receptor
      agonist adenosine given during a surgical procedure seem to decrease
      postoperative pain and requirements for postoperative analgesia. This apparent
      contradiction must be analysed further. Several drugs commonly used to treat
      postoperative pain, such as opioids, NSAIDs, ketamine and paracetamol, are linked
      to nitric oxide (NO) in their mechanism of action. The biosynthesis of NO in the
      central nervous system (CNS) is tonically involved in the nociceptive processing.

PMID- 7632420
TI  - Visceral pain: mechanisms of peripheral and central sensitization.
AB  - This paper describes the responses of peripheral and central visceral nociceptive
      systems to acute injury and discusses these observations in relation to the
      concept of 'pre-emptive analgesia'. Visceral nociceptors are known to respond to
      injury but are also known to become sensitized to non-noxious stimuli during the
      inflammatory process that follows intense noxious stimulation. The afferent
      barrages triggered in visceral nociceptors by the acute injury and the enhanced
      responses evoked in sensitized nociceptors during the repair process can, in
      turn, increase the excitability of central nociceptive systems. The maintenance
      of central hypersensitivity is, however, dependant on the continuing presence of
      afferent volleys from sensitized nociceptors because the central changes cannot
      be sustained in the absence of a peripheral drive. Therefore it is proposed that
      the concept of 'pre-emptive analgesia', as such, has no neurophysiological basis.
      Any analgesic procedure aimed at reducing postoperative pain must not only
      prevent the arrival in the CNS of the initial afferent barrage evoked in
      nociceptive endings but also reduce or eliminate the persistent discharges of
      sensitized nociceptors during the inflammatory repair process that are critically
      important for the maintenance of the central pain state.

PMID- 7632421
TI  - Role of the sympathetic nervous system in acute pain and inflammation.
AB  - The sympathetic nervous system serves not only to regulate involuntary functions,
      but also appears to play an important part in modulating sensory processing.
      While studies in animal models of neuropathic pain and clinical observations
      point to a role of the sympathetic nervous system in certain chronic pain states,
      the function of the sympathetics in postoperative pain and inflammation is
      debatable. Behavioural studies in rats point to a contribution of the sympathetic
      postganglionic terminal in the hyperalgesia of cutaneous inflammation and the
      severity of arthritis. An indirect effect of noradrenaline and inflammatory
      mediators via the release of prostaglandins has been postulated.
      Neurophysiological studies of nociceptors in rats and psychophysical studies in
      humans have failed to provide confirmatory evidence for the role of the
      sympathetic efferents in inflammatory pain and hyperalgesia. The clinical
      significance of the potential interaction of the sympathetic nervous system and
      the somatic afferent system needs further investigation.

PMID- 7632422
TI  - Pre-emptive analgesia: a systematic review of clinical studies.
AB  - Basic scientific evidence suggests that an analgesic intervention made before
      surgery will produce a better outcome than the same intervention made after
      surgery. The evidence from randomized controlled trials (RCTs) which tested this
      hypothesis in patients is reviewed. Four studies with paracetamol or NSAIDs did
      not show any pre-emptive effect. Of seven studies with local anaesthetic six did
      not show a pre-emptive effect. In the four studies with opioids there was weak
      evidence of a pre-emptive effect in three. There are few perfect RCTs, and
      unfortunately this rule applies in the pre-emptive analgesia field. Many of the
      studies which did not show a pre-emptive effect lacked power. The opioid studies
      which did show a pre-emptive effect had other technical weaknesses. One way to
      combat lack of power would be to combine data (meta-analysis). This is very
      difficult in this field because of the outcome measures which investigators are
      using.

PMID- 7632423
TI  - Synergism between analgesics.
AB  - The concept and value of 'multimodal' or 'balanced' analgesia in the treatment of
      postoperative pain is reviewed. Based upon the relatively few multimodal studies
      compared to unimodal studies, it is concluded that a combination of analgesics
      will improve pain relief including movement-associated pain. Since analgesic
      combination therapy is rational, further studies are needed to evaluate the
      optimal combination for each surgical procedure, as well as to assess the risk of
      side effects and need for surveillance in large-scale studies.

PMID- 7632424
TI  - Spinal antinociception: clinical aspects.
AB  - Recent research has demonstrated the increasing importance of the spinal cord in
      processing and modulating nociceptive input. Different groups of drugs, each
      acting by a unique mechanism, have been shown to block nociceptive afferent
      transmission. None of the currently available spinally administered local
      anesthetics, opioids or non-opioids produce analgesia without side effects. Non
      opioids such as alpha-2-adrenergic agonists may be more suited as adjuvants
      rather than sole analgesic agents and their main role lies in reducing the dose
      requirements of other analgesics. Spinal somatostatin and ketamine may have
      neurotoxic potential. The role of these drugs and of midazolam in pain management
      appears to be limited. Preliminary results suggest that the neuropeptide
      octreotide has potent analgesic effects. 'Balanced spinal analgesia' using a
      combination of low doses of drugs, with separate but synergistic mechanisms of
      analgesia, may produce the best results. The optimal drug combinations and
      dosages remain to be determined. It is essential that animal neurotoxicity
      studies followed by controlled clinical trials are performed before widespread
      spinal administration of new drugs.

PMID- 7632425
TI  - New developments in patient-controlled postoperative analgesia.
AB  - Patient-controlled analgesia (PCA) is a newer technique for pain management.
      Patients are allowed to self-administer small analgesic bolus doses into a
      running intravenous infusion, intramuscularly, subcutaneously or even into the
      epidural space. Demands are usually controlled by computer-driven infusion pumps,
      but can also be delivered by disposable devices. Clinical experience demonstrates
      that individual variability in pain sensitivity and analgesic needs are of utmost
      importance. In contrast to earlier expectations, opioid consumption is usually
      higher than with restrictive conventional dosing regimes, but without an increase
      in serious side effects. Patients' acceptance is generally enthusiastic because
      of the possibility of self-control. PCA has proved its importance for pain
      studies, e.g. for algesimetry, to determine predictors of postoperative pain, to
      describe drug interactions, to evaluate the concept of pre-emptive analgesia or
      for pharmacokinetic designs. It is concluded that PCA results have been urgently
      required in order to change the mind of physicians and nursing staff with respect
      to individual pain management strategies. Once this goal is achieved, PCA
      concepts should also be used for the improvement of more conventional techniques.

PMID- 7632426
TI  - Anaerobic infections in children with neurological impairments.
AB  - Children with neurological impairments are prone to develop serious infection due
      to anaerobic bacteria. They often are predisposed to develop infections caused by
      their own indigenous bacterial flora caused by impairments of their mechanical
      and immunological defenses, the change in their oral flora due to poor hygiene,
      and the delay in recognition of acute infection. The most common anaerobic
      infections are decubitus ulcers, gastrectomy site wound infections, pulmonary
      infections (aspiration pneumonia, lung abscesses, and tracheitis), and chronic
      suppurative otitis media. The unique microbiology of each of the infections and
      their medical and surgical management were discussed in this review.

PMID- 7632427
TI  - Medical disorders of adults with mental retardation: a population study.
AB  - This study was conducted to determine the frequency of medical disorders in
      people with mental retardation. The prevalence of mental retardation among
      adults, ages 20 to 50 years, living in Northern Sydney, was determined, and 202
      persons were randomly selected for medical examination. Compared to the local
      population, the study group had significantly increased cardiovascular risk
      factors, rate of medical consultation, rate of hospitalization, and mortality.
      The research sample had an average 5.4 medical disorders per person, half of
      which had not been detected previously. We concluded that the provision of health
      care to adults with mental retardation needs to be improved.

PMID- 7632428
TI  - Cerebral specialization for spatial processing in adults with Down syndrome.
AB  - Cerebral specialization for spatial processing in adults with Down syndrome was
      examined. In the first experiment, both control and right-handed subjects with
      Down syndrome exhibited no lateral advantage in a dihaptic shape-matching task,
      whereas left-handed subjects with Down syndrome displayed an expected left-hand
      advantage. In a visual field dot enumeration task in the second experiment, all
      groups exhibited left-field superiority. Thus, atypical cerebral organization of
      function in adults with Down syndrome appears to be confined to speech perception
      (Elliott & Weeks, 1993).

PMID- 7632429
TI  - Detection of Alzheimer disease in individuals with Down syndrome.
AB  - A comprehensive baseline of emotional functioning was established for adults with
      Down syndrome. Five emotional factors were studied using groups of (a) adults
      with Down syndrome (n = 30), (b) clinical control subjects with dementia of the
      Alzheimer type (n = 18), and (c) elderly control subjects without mental
      retardation (n = 25). Results of planned statistical comparisons showed
      indifference, pragnosia, and inappropriateness as primary emotional factors
      separating Down syndrome and Alzheimer disease groups from elderly control
      subjects without mental retardation. Indifference was also shown to covary with
      cognitive mental state, whereby increased levels of indifference were associated
      with decreased levels of cognitive functioning. The possibility of noncognitive
      variables signalling dementia of the Alzheimer type in individuals with Down
      syndrome was discussed.

PMID- 7632430
TI  - Quality of life in applied research: a review and analysis of empirical measures.
AB  - A consensus list of 15 dimensions and corresponding components of quality of life
      was derived from the literature and proposed as a conceptual model. Eighty-seven
      empirical studies found in the applied research then were analyzed, and the
      proposed model was found to be supported by 1,243 empirical measures. In
      addition, studies were analyzed with respect to (a) demographic variables, (b)
      type of investigation, (c) method of assessment, (d) psychometric properties of
      assessments used, and (e) common dimensions of measures investigated and their
      frequency of measurement. Based upon findings, issues regarding methodology,
      implications for policy and practice in the field, and recommendations for future
      research were discussed.

PMID- 7632431
TI  - Attractor dimensions of behavior state changes among individuals with profound
      disabilities.
AB  - Accumulating evidence indicates that many physiological and psychological
      processes behave in nonlinear ways, and some developmental researchers have
      recommended that behavior states should also be investigated within this
      framework. We examined state transitions for evidence of nonlinearity among 66
      subjects with profound disabilities. States were observed during continuous
      periods of 5 hours for each subject. Data were analyzed as percentage time
      subjects spent in various states, influence of environmental variables, and
      evidence of nonlinear state transitions. Twenty of three subjects demonstrated
      chaotic state trajectories, but there appeared to be no observed characteristics
      that differentiated them from other participants. Findings suggest complex
      behavioral processes in the levels of alertness and responsiveness associated
      with some individuals with profound disabilities. Implications for other
      populations and physiological measures were discussed.

PMID- 7632432
TI  - The United Kingdom population with Down syndrome: present and future projections.
AB  - The prevalence of Down syndrome by age and sex was established from
      questionnaires sent to heads of 30 registers in the United Kingdom covering a
      general population of over 7 million. Possible underascertainment and factors
      affecting prevalence were discussed. The overall prevalence of Down syndrome in
      the United Kingdom was 6.7 per 10,000 general population, representing
      approximately 30,000 affected individuals. Prevalence was also presented in 5
      year age bands. We used two methods of projection and found no significant
      difference in their results. There was no indication of a sizable reduction in
      the future Down syndrome population. An incidence- and mortality-based projection
      method provided evidence that recent reductions in prevalence among the youngest
      age bands may be explained by changes in the maternal population.

PMID- 7632433
TI  - Modelling of drug penetration into human skin using a multilayer membrane system.
AB  - In this article, a new in vitro model system is presented with a multilayer
      membrane system serving as acceptor. Matrix-stabilized membranes are applied with
      dodecanol as lipid and collodion as matrix. Using the drug dithranol it was shown
      that the acceptor system can be varied over a wide range by changing the
      dodecanol content of the membranes and by addition of the hydrophilic substance
      propylene glycol to the membranes. It was demonstrated that the variability of
      the acceptor system can be used to adapt the penetration profiles of dithranol in
      a six-layer membrane system to those in excised human skin. It is shown that it
      is possible to study the penetration of dithranol from different semisolid
      formulations using the 'adapted' model system.

PMID- 7632434
TI  - Effect of benzoyl peroxide on protein kinase C in cultured human epidermal
      keratinocytes.
AB  - Benzoyl peroxide (BzPO) has been the most widely used topical agent for acne
      since the 1960s. This is true despite numerous reports that BzPO can enhance the
      development of carcinomas from murine epidermal papillomas. Because activation of
      protein kinase C (PKC) is considered to mediate cellular responses to other
      epidermal tumor promotors, we wished to investigate the relationship between BzPO
      and PKC in cultured human epidermal keratinocytes (NHEK). We assayed (a) direct
      effects of BzPO on PKC activity in a cell-free system using semipurified human
      keratinocyte PKC, (b) BzPO effects on the subcellular distribution of PKC, and
      (c) BzPO modulation of NHEK proliferation and phorbol ester-induced
      differentiation. NHEK maintained in serum-free media (0.15 mM Ca2+) were treated
      with concentrations of BzPO in acetone from 100 nM to 500 microM, with
      concentrations of acetone not exceeding 0.1%. No short-term translocation of PKC
      from cytosol to membrane was observed at any BzPO concentration. BzPO did not
      downregulate subcellular levels of PKC activity after 24 h of exposure. BzPO did
      not significantly antagonize phorbol ester-induced inhibition of proliferation or
      differentiation but did weakly antagonize Ca(2+)-induced differentiation.
      Consistent with a PKC-mediated mechanism for Ca(2+)-induced differentiation, BzPO
      inhibited both human and murine PKC in a cell-free system. These results suggest
      that BzPO does not promote malignant conversion through a PKC-dependent
      mechanism, and in fact, inhibits PKC activity in vitro.

PMID- 7632435
TI  - Effects of selenium on UVA-induced lipid peroxidation in cultured human skin
      fibroblasts.
AB  - The effect of selenium on the lethal action of ultraviolet radiations and on the
      lipid peroxidation induced by exposures to ultraviolet A (320-400 nm; 360 kJ.m-2)
      and ultraviolet B (290-320 nm; 2 kJ.m-2) have been measured in cultured human
      skin fibroblasts. The experiments have been performed with either pure selenium
      or a spring water containing selenium and other trace elements (zinc and
      strontium). For cells cultured in a standard medium containing 10% fetal calf
      serum, no effect of selenium or spring water addition to the culture medium was
      observed on the lethality or on the peroxidative process induced by ultraviolet A
      and B radiations. Concurrently, there was no detectable increase of the seleno
      dependent glutathione peroxidase activity. For cells previously depleted in
      selenium by a culture in a medium containing only 2% serum, a protective effect
      of selenium can be detected. Depending on the fibroblast donor, we observed (1) a
      protective effect on lethality of dividing fibroblasts induced by ultraviolet A
      radiations, (2) a protective effect on lipid peroxidation induced by ultraviolet
      A radiations on dividing or quiescent fibroblasts and (3) an increase in
      glutathione peroxidase activity in fibroblasts.

PMID- 7632436
TI  - Inhibition of cytokine gene expression in mouse skin by subcutaneous injection of
      cyclosporine.
AB  - Cyclosporine A (CsA) has been shown to be an effective therapeutic agent for a
      wide variety of cutaneous diseases yet its exact mechanism of action is still
      unclear, although one well-defined effect of CsA is the inhibition of T-cell
      derived cytokine expression. We recently demonstrated in vitro that CsA inhibits
      cell proliferation and suppresses cytokine gene expression in keratinocytes. In
      this study, we report the in vivo effects of CsA on skin cytokine gene expression
      as determined by reverse-transcriptase polymerase chain reaction. C57BL6 mice
      (female, 8-10 weeks old) were subcutaneously injected with CsA in olive oil (0, 5
      and 10 mg/kg) every other day for 3 weeks. Treatment with 5 mg/kg CsA inhibited
      both interleukin (IL)-1 alpha and tumor necrosis factor alpha gene expression by
      about 70 and 90%, respectively, relative to vehicle control levels. However, IL-6
      gene expression did not significantly change. Injection of 10 mg/kg CsA inhibited
      expression of all three genes by 80-90% relative to control levels. These data
      show that CsA can inhibit constitutive cytokine gene expression in mouse skin.

PMID- 7632437
TI  - Treatment of porphyria cutanea tarda by the effect of chloroquine on the liver.
AB  - Porphyria cutanea tarda (PCT) is characterized by cutaneous symptoms in
      association with hepatic accumulation and urinary excretion of mainly uro- and
      heptacarboxyporphyrins. 24 PCT patients excreting urinary porphyrins between 1.9
      and 5.8 mumol/24 h (normal < 0.2) were treated with chloroquine at a dose of 125
      mg twice a week. During the first phase of therapy urinary porphyrin excretion
      transiently increased 1.1- to 2.9-fold indicating a phase of mobilization. A
      slight initial elevation was also found regarding the activities of serum
      aminotransferases reflecting the hepatotoxic effect of chloroquine. The clinical
      symptoms disappeared after a period ranging from 2 to 6 months, and after an
      average of 12 months the porphyrin excretion in all patients had returned to
      nearly normal values.

PMID- 7632439
TI  - Reproductive isolation between Drosophila lini and its siblings.
AB  - Courtship behavior and reproductive isolation between nine strains of Drosophila
      lini and its siblings from Taiwan (TWN), Dinghushan (DHS) and Nankunshan (NKS) in
      China, and Pyinoolwin (MMY) and Yangon (RGN) in Myanmar were investigated. No
      premating and postmating isolation between the Taiwan and mainland China strains
      were found. Crosses between mainland China (DHS and NKS) or the TWN strain and
      the MMY or RGN strain produced fertile F1 hybrid females and sterile F1 hybrid
      males. Crosses between MMY strains and RGN strains which showed strong premating
      isolation produced either no F1 hybrids, or fertile F1 hybrid females and sterile
      males in some cases. These results suggest the existence of at least three
      genetically distinct sibling species of D. lini.

PMID- 7632438
TI  - Effects of human recombinant interferon-alpha 2b on P450-dependent isozymes in
      rat liver and skin.
AB  - Adult female Wistar rats divided into two groups (6 animals each) were
      subcutaneously treated with 10(5) units/day recombinant human interferon-alpha 2b
      (hrIFN-alpha 2b) and corresponding quantities of the vehicle, respectively, over
      a period of 7 days. Microsomal protein, P450 content, and the activities of
      aminopyrine-N-demethylase (ADM), 7-ethoxyresofurin-O-deethylase (7-ERO-D) and of
      erythromycin-N-demethylase (EMDM) were determined in the liver microsomes.
      Moreover, 7-ERO-D and EMDM activities were determined in the skin microsomes of
      the treated animals. In the liver microsomes hrIFN-alpha 2b caused a
      statistically significant increase in ADM activity and a statistically
      significant decrease in 7-ERO-D and EMDM activities, as compared to the controls.
      However, in the pooled skin microsomes 7-ERO-D activity showed a trend to
      increase under the administration of hrIFN-alpha 2b, whereas EMDM activity could
      not be detected in the treated or the control animals. The results of the present
      study indicate that hrIFN-alpha 2b is capable of affecting the activities of P450
      dependent isozymes in the rat liver and skin in a different manner. Our findings
      support the hypothesis that clinically relevant interactions may occur during the
      concomitant administration of hrIFN-alpha 2b and other compounds that are
      metabolized by hepatic and cutaneous P450 monooxygenases.

PMID- 7632440
TI  - Genetic variation and geographic distribution on the mitochondrial DNA in local
      populations of the musk shrew, Suncus murinus.
AB  - The musk shrew (Suncus Murinus) is widely distributed throughout Asia and East
      Africa. The mitochondrial DNA (mtDNA) of this species was analyzed in individuals
      from 31 local populations in nine Asian countries and Mauritius, using 17
      restriction endonucleases. Although fourteen and nine mtDNA haplotypes were
      detected from Bangladesh and Nepal, respectively, one to four haplotypes were
      found in each Southeast Asian country, and one common haplotype existed in Japan,
      Philippines, Vietnam, Thailand and Indonesia. Clustering analysis of mtDNA
      haplotypes classified shrew populations to three groups--continental group
      (Bangladesh and Nepal), islands' group (insular countries and Vietnam) and Malay
      group. The average nucleotide diversity among these three groups was calculated
      to be about 3.5%. These results indicate that the origin of feral populations in
      this species might be old and their population sizes are extremely large in the
      continent, and suggest a rapid spread of this animal throughout the islands.
      Although we have not shown yet an evidence of close relationships between
      islands' and continental mtDNA haplotypes, it is likely that the musk shrew had
      migrated from the continent in South Asia to the islands in Southeast Asia
      recently.

PMID- 7632441
TI  - Genetic studies on premating isolation in Drosophila simulans. I.AD. simulans
      line highly crossable with D. melanogaster.
AB  - The S2 line of Drosophila simulans, an isofemale line from a natural population
      at Mishima, Japan, was found to have high crossability with D. melanogaster. Over
      80% of the S2 females mated with D. melanogaster males, while only 2.4- 14.2% of
      control females from other D. simulans lines mated. The reciprocal mating (D.
      melanogaster female x S2 males) was in normal range (35-50%). The crossability of
      the F1 females between the S2 and other normal simulans lines was slightly higher
      than the control females. The high crossability is caused by at least two genes,
      one on the second and the other on the third chromosome which act additively.

PMID- 7632442
TI  - Nucleotide substitution type dependence of generation time effect of molecular
      evolution.
AB  - Using DNA sequence data of 18 genes from 14 mammals, we analyzed how the average
      molecular evolution rate per year per site (Vy) depends on the generation time
      (g). (I) Assuming the relation Vy varies; is directly proportional to g(-alpha),
      the index of generation time effect, (alpha) was estimated to be about 0.14 for
      amino acid replacement substitutions (A), and about 0.32 for synonymous
      substitutions (S). (II) Assuming the relation Vy = V(m)g g-1 + V(e)y, where V(m)g
      and V(e)y are constant independent of g, the fraction, r(e) = V(e)y/Vy, of the
      mutation rate independent part (V(e)y) in the total evolution rate (Vy) was
      estimated under the assumptions of the star phylogeny and the constancy of the
      mutation rate per generation. r(e) was smallest for mouse with the shortest
      generation time among our analyzed species, and it was estimated to be about 0.57
      for A and 0.31 for S. Both results do not support the view that Vy is equal to
      the neutral mutation rate per site both for A and for S. They are in line with
      the thesis that, at least for A and probably even for S, the molecular evolution
      rate is influenced by some causes other than the mutation rate, such as changing
      environment.

PMID- 7632443
TI  - A conditional negative selection for Arabidopsis expressing a bacterial cytosine
      deaminase gene.
AB  - The enzyme activity for cytosine deaminase, which converts cytosine to uracil in
      bacterial, is usually undetected in higher plants and animals. The enzyme also
      catalyzes conversion of non-toxic 5-fluorocytosine (5-FC) to 5- fluorouracil (5
      FU), a toxic compound for plant growth. The gene encoding cytosine deaminase
      (codA) from Escherichia coli was fused to cauliflower mosaic virus (CaMV) 35S
      promoter (P35S), and cloned into a binary vector pLABR101. The resulting plasmid
      pLABR102 contained two marker genes for plants: a positive marker gene, bialaphos
      resistance (bar) gene driven by the promoter from nopaline synthase gene (Pnos)
      and a negative one, P35S-codA. The binary vector pLABR102 was transformed into
      Arabidopsis thaliana via Agrobacterium-mediated transformation. In transgenic
      progenies (T3) of the second (T2) generation heterozygous for a single T-DNA
      insertion, a 3:1 segregation ratio was observed on both bialaphos (resistance to
      sensitive) and 5-FC (sensitive to unaffected). From T2 plants homozygous for the
      T-DNA insert, on the other hand, no segregation was detected: all the T3
      seedlings were resistant to bialaphos and sensitive to 5-FC. PCR and Northern
      analyses showed that the 5-FC sensitivity in transgenic descendants was caused by
      the integration and expression of the chimeric codA gene in the Arabidopsis
      genome. The results indicated that cytosine deaminase from E. coli is functional
      and useful for negative selection in Arabidopsis, and that sensitivity to 5-FC as
      well as the positive bialaphos resistance are dominant traits in Arabidopsis.

PMID- 7632444
TI  - Cloning and characterization of cDNAs for 70-kDa heat-shock proteins (Hsp70) from
      two fish species of the genus Oryzias.
AB  - cDNA corresponding to two hsp70-related genes (OLHSC70 and CEHSC70) were isolated
      from two lines of cultured fish cells derived from the genus Oryzias. OLHSC70 was
      2,261 bp in length and encoded a protein of 686 amino acids with a predicted
      molecular mass of 76,120 daltons. CEHSC70 was 2,114 bp in length and it lacked
      the 5' region found in OLHSC70. Two-dimensional electrophoresis revealed that
      Oryzias latipes has at least three heat-inducible proteins with molecular masses
      of about 70,000 daltons. One of these proteins (Hsp70.1) was barely expressed
      under normal conditions but its high-level expression was induced by
      hyperthermia. The other two proteins (Hsc70.1, and Hsc70.2) were constitutively
      expressed under normal conditions and only slightly enhanced levels were induced
      by hyperthermia. Transfection with the cloned sequence, RNA dot-blot analysis and
      the two-dimensional electrophoresis of proteins showed that OLHSC70 encoded
      Hsc70.1.

PMID- 7632445
TI  - Drug use prevalence in a rural school-age population: the New Hampshire survey.
AB  - Pre-adolescent and adolescent drug use is a major public health concern in the
      United States. Although we have good prevalence data on some adolescents, we have
      little information on pre-adolescents, young adolescents, and rural children. We
      conducted a survey of 4,406 children in grades 4-12 in rural New Hampshire in
      1990. Students completed annual self-report surveys on demographic
      characteristics, drug use, and psychosocial risk factors. These children are
      initiating drug use in elementary school. Alcohol is the preferred drug for both
      genders at all grade levels, followed by cigarettes, marijuana, and spitting
      tobacco. Current use of these drugs escalates in the sixth through ninth grades.
      Lifetime prevalence and 30-day prevalence increase slowly through high school.
      Most children who are going to use drugs have begun by the tenth grade. In this
      rural state, children's drug preferences are similar to those of other pre
      adolescents and adolescents. Rural students have equal, and in some cases higher,
      lifetime and current use prevalence of alcohol, marijuana, and tobacco in
      comparison with national samples.

PMID- 7632446
TI  - Characteristics of persons with late AIDS diagnosis in the United States.
AB  - To describe characteristics of persons with late (at or after death) acquired
      immunodeficiency syndrome (AIDS) diagnosis, we analyzed national surveillance
      data among all persons with AIDS diagnosed through December 1991 under the pre
      1993 AIDS case definition and with a known date of death. Late diagnosis was
      present in 15.8% of 163,202 decreased persons with AIDS and in 15.3% of decreased
      men with AIDS, 20.6% of women, 12.1% of whites, 20.0% of blacks, 21.1% of
      Hispanics, 12.3% of men who have sex with men (MSM), 21.9% of injecting drug
      users (IDU), and 19.6% of persons exposed to human immunodeficiency virus (HIV)
      through heterosexual contact. When age, race/ethnicity, sex, geographic region,
      and transmission mode were included in logistic regression analyses, among
      adults/adolescents, late diagnosis was more likely among persons 40 years or
      older than among those 13-39 years old, among blacks and Hispanics than among
      whites, and among IDU and persons exposed to HIV through heterosexual contact
      than among MSM. Although children (less than 13 years of age) were more likely to
      have late diagnosis than adults and adolescents, late diagnoses among children
      did not differ significantly by race/ethnicity, sex, geographic region, or
      transmission mode. Late AIDS diagnosis, especially among ethnic minorities and
      IDU and their sex partners, may represent delays in HIV diagnosis and care. In
      addition to not receiving early clinical intervention, persons who are diagnosed
      later in the course of HIV disease represent missed opportunities for receiving
      prevention efforts such as education, counseling, and substance abuse
      treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7632447
TI  - A randomized trial of the IMPACT worksite cholesterol reduction program.
AB  - To evaluate the incremental effectiveness of a worksite cholesterol control
      management program when added to an established, comprehensive health promotion
      program at the worksite, we conducted a randomized, controlled trial including
      both blue- and white-collar employees at four geographically dispersed worksites.
      One hundred twenty-seven employees with serum cholesterol levels of 240 mg/dL or
      greater were assigned to receive an enhanced intervention program (the IMPACT
      program) while 125 were assigned to a regular screening and referral group, which
      included a comprehensive worksite health promotion program. One hundred eighteen
      program and 116 control subjects had one-year follow-up measures recorded. We
      used venipuncture specimens to obtain standardized baseline and follow-up
      cholesterol measures. Program subjects experienced a mean decline of 16.6 mg/dL
      as compared to a decline of 10.0 mg/dL in control subjects. The crude intergroup
      difference was 6.6 mg/dL (95% confidence internal [CI] = 1.1, 14.3), while the
      adjusted difference was 6.9 mg/dL (95% CI = 0.5, 14.3). Neither difference was
      significant at the .05 level. The percentage of program subjects who reduced
      their cholesterol level to below 240 mg/dL (36%) was significantly greater than
      the corresponding percentage among control subjects (21%). The enhanced worksite
      cholesterol control program provided incremental benefit in the percentage of
      individuals with elevated cholesterol in a population already exposed to a
      comprehensive worksite health promotion program that includes regular cholesterol
      screening, referral, and education activities.

PMID- 7632448
TI  - California's "5 a day--for better health!" campaign: an innovative population
      based effort to effect large-scale dietary change.
AB  - The annual toll of diet-related diseases in the United States is similar to that
      taken by tobacco, but less progress has been achieved in reaching the Public
      Health Service's Healthy People 2000 objectives for improving food consumption
      than for reducing tobacco use. In 1988, the California Department of Health
      Services embarked upon an innovative multi-year social marketing program to
      increase fruit and vegetable consumption. The 5 a Day--for Better Health!
      Campaign had several distinctive features, including its simple, positive,
      behavior-specific message to eat 5 servings of fruits and vegetables every day as
      part of a low-fat, high fiber diet; its use of mass media; its partnership
      between the state health department and the produce and supermarket industries;
      and its extensive use of point-of-purchase messages. Over its nearly three years
      of operation in California, the 5 a Day Campaign appears to have raised public
      awareness that fruits and vegetables help reduce cancer risk, increased fruit and
      vegetable consumption in major population segments, and created an ongoing
      partnership between public health and agribusiness that has allowed extension of
      the campaign to other population segments, namely children and Latino adults. In
      1991 the campaign was adopted as a national initiative by the National Cancer
      Institute and the Produce for Better Health Foundation. By 1994, over 700
      industry organizations and 48 states, territories, and the District of Columbia
      were licensed to participate. Preventive medicine practitioners and others
      involved in health promotion may build upon the 5 a Day Campaign experience in
      developing and implementing efforts to reach the nation's dietary goals.

PMID- 7632449
TI  - The information age confronts an age-old problem.

PMID- 7632450
TI  - It is time to get serious about childhood injury surveillance in the United
      States.

PMID- 7632451
TI  - View from Washington: victories in a lost war-lessons for prevention from the
      103rd Congress.

PMID- 7632452
TI  - A change of venue.

PMID- 7632453
TI  - Monitoring maternal mortality using vital records linkage.
AB  - We developed a method to identify maternal deaths (deaths to women within 365
      days of delivery) by linking Tennessee vital records. A computerized algorithm
      compared personal identifiers from the death certificates of reproductive-aged
      women to maternal identifiers on birth and fetal death certificates. For each
      decedent record which met the study criteria, the algorithm calculated a "match
      score" by comparing common elements in both files. The algorithm awarded full
      credit for data elements that agree exactly, partial credit for elements in
      partial agreement, and subtracted credit for information that mismatched. Match
      scores ranged from 0 to 35 for the 9,009 deaths in women 10-55 years of age
      during the three study years, with the majority of scores (96.3%) being 0 for "no
      match." Match scores of 1 to 8 were obtained by 153 (1.7%) of decedent records,
      while scores greater than 9 were obtained by 184 (2.0%) of decedent records. We
      used nurse-abstracted hospital, autopsy, and coroner records as our standard to
      verify the linkages. Manual review of personal identifiers showed that scores of
      12 or less were not a match while scores of 13 or more indicated "true" matches.
      Based on this cutoff, the linkage algorithm yielded 130 maternal deaths. Of
      these, 32 (25%) were classified as truly pregnancy-related upon medical record
      review by an obstetrician. The remaining 98 deaths were associated only
      temporally with pregnancy. During the same time period, 16 individuals were
      identified to the State Health Department on their death certificates as dying
      from pregnancy-related causes, including one not identified by the linkage
      process.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7632454
TI  - Determinants of prenatal care use in Hawaii: implications for health promotion.
AB  - This study examines the association between maternal sociodemographic
      characteristics and the receipt of different levels of prenatal care use (no
      care, inadequate, intermediate, adequate) in order to determine different
      patterns in the relationships between maternal characteristics and these distinct
      categories of prenatal care use. Using the 1979-1992 Hawaii live birth vital
      record file, single live births to Hawaii resident mothers of white,
      Hawaiian/part-Hawaiian, Filipino, or Japanese ethnicity, who did not indicate on
      the birth certificate that either parent was active duty military, were selected.
      Over one quarter of this study population did not initiate prenatal care in the
      first trimester. Given the high level of insurance coverage found in Hawaii, this
      finding is disconcerting, particularly in relation to the U.S. Year 2000
      Objective of 90% initiation in the first trimester. Overall, the factors that
      predicted receipt of any prenatal care predicted more adequate use of prenatal
      care as well. Noteworthy exceptions were maternal age and ethnicity. Identifying
      these exceptions is important for the development of a more detailed
      understanding of risk factors related to use of prenatal care to better target
      program responses aimed at improving prenatal care use. In addition, these data
      suggest that removing financial barriers to access to care does not guarantee
      universal use of disease prevention and health promotion services.

PMID- 7632455
TI  - Smoking relapse prevention counseling during prenatal and early postnatal care.
AB  - Our objective was to examine the efficacy of the added effect of individualized
      smoking relapse prevention counseling on obstetricians' and nurse midwives' usual
      advice during prenatal care. One hundred and seventy-five pregnant women who were
      smoking early in their pregnancy, but had quit by first prenatal visit, were
      randomly assigned to receive the usual advice from their obstetrician or nurse
      midwife, or usual advice plus individual relapse prevention counseling. Smoking
      status was measured by self-report, by urinary cotinine/creatinine ratio at the
      36-week visit, and by self-report at long-term postpartum follow-up. We found
      that a smaller percentage of women in the intervention group (8.8%) reported
      smoking at the thirty-sixth-week visit than those in the usual care group
      (16.9%), a nonsignificant difference. No significant difference in relapse rates
      during pregnancy was observed based on urinary cotinine/creatinine ratios, but
      these rates, 29.5% and 27.9% respectively, were substantially higher than those
      based on self-report. The average number of days abstinent reported by women in
      the intervention group was significantly longer than that in the usual care
      group, 199 days versus 166 days respectively (P < .01). Logistic regression
      analysis indicated that longest time abstaining before first visit, level of
      belief in smoking's harm to the fetus, and motivation to smoke were independently
      related to the probability of relapsing to smoking by the 36-week visit. Long
      term relapse rates were not significantly different: intervention group, 50.9%,
      usual care group, 50.0%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7632456
TI  - Validity of Pap smear and mammogram self-reports in a low-income Hispanic
      population.
AB  - This study measures the validity of self-reported mammography and Pap smear usage
      in Mexican-American women. We compared Pap smear and mammography reports in
      medical records to self-reports obtained in a household survey of 450 women in El
      Paso, Texas. The women were generally low-income, older, and Spanish-speaking.
      Forty-six percent of self-reported Pap smears in the previous year were verified
      (60.8% within previous two years, 67.1% within previous three years). Forty-nine
      percent of self-reported mammograms within the previous year were verified (74.7%
      within previous two years). For both Pap smears and mammograms, twice as many
      tests in the past five years were reported as were documented. Self-reports of
      Pap smears at a public health clinic were more valid than those at other sites.
      Denials of mammography within the past five years were more accurate (97.5%) than
      denials of Pap smears (81.8%). We conclude that self-reports of mammograms and
      Pap smears in Mexican-American women greatly overestimate the prevalence of
      screening. Intensive cancer prevention activities in this population are needed
      to approach the Year 2000 Objectives set by the U.S. Department of Health and
      Human Services.

PMID- 7632457
TI  - Medically attended nonfatal injuries among preschool-age children: national
      estimates.
AB  - We used data from the 1991 Longitudinal Follow-up to the National Maternal and
      Infant Health Survey to examine cumulative risk of injury among children from
      birth to three years old and to provide national-level cause-specific estimates
      of medically attended nonfatal injuries for this age group. Almost 25% of the
      8,145 children reportedly received care for an injury between birth and three
      years old. Among the children with injuries, 25.4% reportedly had more than one
      medically attended injury. Risk of reported injury was higher for boys and upper
      level socioeconomic groups. Falls were the most frequently reported injury (51%),
      followed by burns (11.7%), striking or cutting injuries (9.8%), poisonings
      (9.8%), and injuries from devices not intended for the child's use (7.9%).
      Nonfatal injuries for preschool-age children present a pattern strikingly
      different from that of fatal injuries among this age group, and the need for this
      data is important in targeting prevention strategies.

PMID- 7632458
TI  - Sequence similarities between latent membrane protein LMP-1 of Epstein-Barr
      virus, integral membrane protein p12I of human T cell leukemia/lymphotropic virus
      type 1, E5 transformation protein of bovine papillomavirus, and the transmembrane
      proteins of slowly transforming retroviruses.

PMID- 7632459
TI  - Phagocytosis of individual CD4+ T cells by HIV-induced T cell syncytia.
AB  - Transmission electron microscopic analysis of HIV-induced syncytia of the CD4+
      SupT1 cell line has revealed profiles of whole T cells in the syncytium
      cytoplasm. Serial sections demonstrate that these T cells are completely
      enveloped by a second membrane in the syncytium cytoplasm and represent
      phagosomes. Pycnosis of engulfed T cell nuclei, vacuolation of the cytoplasm of
      engulfed T cells, and the association of engulfed T cells with dense vesicular
      clusters in the syncytium cytoplasm support the conclusion that they represent
      phagosomes. In addition, transmission electron micrographs of the syncytium
      surface reveal giant pseudopodial extensions wrapping around T cells, in a
      fashion similar to bacterial and yeast phagocytosis by professional phagocytes.
      These results suggest that phagocytosis is a characteristic acquired during HIV
      induced syncytium formation, and that it may represent an avenue of T cell death
      in addition to fusion in HIV-infected SupT1 cell cultures.

PMID- 7632460
TI  - HIV type 1 Tat protein induces apoptosis and death in Jurkat cells.
AB  - Jurkat cells stably expressing high levels of the HIV-1 Tat protein were
      generated after transfection with an Epstein-Barr virus-based episomal replicon
      and selection in hygromycin B. The Jurkat Tat transfectants exhibited a longer
      doubling time when compared to Jurkat cells or Jurkat cells transfected with the
      control parent plasmid. Cell cycle analysis revealed comparable durations of each
      phase of the cell cycle in the Tat and control transfectants. Flow cytometric
      analysis using Hoechst 33342 and propidium iodide staining revealed that the Tat
      transfectants exhibited a higher percentage of apoptotic cells when compared to
      the control transfectants (29.1 +/- 3.1 vs. 11.43 +/- 3.1%). Incubation of Jurkat
      cells with recombinant HIV-1 Tat protein resulted in induction of apoptosis. The
      HIV-1 Tat protein induces apoptosis in a CD4-positive T cell line. Tat-induced
      programmed cell death may contribute to the lymphocyte depletion seen in persons
      infected with HIV-1.

PMID- 7632461
TI  - Cystamine inhibits HIV type 1 replication in cells of monocyte/macrophage and T
      cell lineages.
AB  - The effects of cysteamine (2-aminoethanethiol, MEA) and its disulfide, cystamine,
      on the human immunodeficiency virus (HIV-1) expression in chronically infected
      promonocytic cells (U1), T cell line (ACH-2), and peripheral blood monocyte
      derived macrophages (MDM) were investigated. U1 and ACH-2 cells constitutively
      express low levels of virus, which is increased by the addition of tumor necrosis
      factor (TNF-alpha), interleukin 6 (IL-6), granulocyte-macrophage-colony
      stimulating factor (GM-CSF), and other inducers. Cystamine, in noncytotoxic
      doses, suppressed in a concentration-dependent fashion the induction of HIV-1
      expression mediated by TNF-alpha, IL-6, GM-CSF, and monokine-enriched monocyte
      culture supernatants in both U1 and ACH-2 cells as determined by HIV-1 reverse
      transcriptase (RT) activity. Similarly, HIV-1 expression was substantially
      reduced in the cystamine-treated primary MDM cultures compared with the untreated
      control cultures. The addition of cystamine into HIV-1 chronically infected MDM
      (12 days after infection was established) also suppressed 80-90% of RT activity
      in comparison to the untreated controls. HIV-1 (Bal) infected MDM cultures
      (without cystamine treatment) demonstrated giant syncytium formation, whereas
      cystamine-treated cultures lacked the giant syncytia induced by HIV-1 infection.
      Cystamine also inhibited LPS-induced TNF production in MDM. In contrast to
      cystamine, cysteamine showed no significant effects on either the monokine
      induced HIV-1 expression in U1 or ACH-2 or acute and chronic HIV-1 infection in
      MDM.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7632462
TI  - Distinct changes in HIV type 1 RNA versus p24 antigen levels in serum during
      short-term zidovudine therapy in asymptomatic individuals with and without
      progression to AIDS.
AB  - Serum HIV-1 RNA and p24 antigen levels were examined in 28 seropositive
      asymptomatic individuals participating in a trial on the efficacy of zidovudine.
      Sixteen individuals remained asymptomatic until 4 years after the onset of the
      trial, whereas 12 individuals were diagnosed with an AIDS-defining event. The
      serum HIV-1 RNA load and p24 antigen levels were determined before the onset of
      therapy and during the first 8 weeks of therapy to establish whether the patterns
      of change were predictive of clinical outcome. Among the 28 participants 43% had
      measurable pretreatment concentrations of p24 antigen. Initiation of zidovudine
      therapy was followed by a similar decline of p24 antigen levels in nonprogressors
      as well as progressors and, therefore, these groups could not be distinguished on
      the basis of this parameter. HIV-1 RNA was detected in the pretreatment samples
      of 82% of the individuals and could be detected in p24 antigen-positive as well
      as p24 antigen-negative individuals. Similar changes in HIV-1 RNA load during
      zidovudine therapy were observed in p24 antigen-positive and -negative
      individuals. Analysis of the HIV-1 RNA response according to clinical outcome
      demonstrated that HIV-1 RNA copy numbers had declined significantly after 4 weeks
      of therapy in both nonprogressors and progressors, but the decline in RNA load
      was much stronger in the nonprogressors. Our data show that the HIV-1 RNA load in
      serum can be used to monitor the response to antiviral therapy in p24 antigen
      positive as well as -negative individuals. Posttreatment changes in p24 antigen
      levels are not indicative for clinical outcome, whereas RNA copy numbers
      are.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7632463
TI  - Anti-HIV type 1 cytotoxic T lymphocyte effector activity and disease progression
      in the first 8 years of HIV type 1 infection of homosexual men.
AB  - Cytotoxic T lymphocytes (CTL) may play an important role in host defense against
      HIV-1 infection. In this study, we examined the responses of circulating effector
      CTL (CTLe) specific for Gag, Pol, Env, and Tat in 57 HIV-1-infected men, 49 of
      whom were asymptomatic and had documented time since seroconversion of < 8 years.
      CTLe responses to at least one of the four HIV-1 gene products were detected in
      83% of the subjects. The magnitude and prevalence of the anti-Tat responses were
      significantly less than the responses to Gag, Pol, and Env. Cell depletion
      studies indicated that the lytic activity against the HIV-1 structural proteins
      was mediated by CD8+ T cells, although 30% of Env-specific lysis was mediated by
      CD16+ natural killer cells. Anti-HIV-1 CTLe responses against Gag and Pol were
      significantly less in subjects infected for over 6 years as compared to those
      infected for shorter periods of time. We found no correlation, however, between
      anti-HIV-1 CTLe responses and either CD4+ or CD8+ T cell counts, rates of CD4+ T
      cell loss, HIV-1 infectious viral load, use of antiviral medications, or
      subsequent progression to AIDS. Our results indicate that anti-HIV-1 CTLe
      activity is relatively stable in asymptomatic subjects infected < 6 years, and is
      not an early marker for risk of disease progression.

PMID- 7632464
TI  - Neutralizing monoclonal antibody against a external envelope glycoprotein (gp110)
      of SIVmac251.
AB  - Three monoclonal antibodies (M318T, M56S and M815) against an external envelope
      glycoprotein (gp110) of simian immunodeficiency virus (SIV) mac251 were obtained
      by immunizing BALB/c mice with recombinant gp110 (rgp110). All three monoclonal
      antibodies reacted with the surface of cells infected with SIVmac251 but not with
      that of uninfected counterparts. The binding activity of these monoclonal
      antibodies against native gp110 was confirmed by means of Western blotting. One
      of them, M318T neutralized SIVmac251 infection both by cell-free and cell
      associated viruses. M318T cross-reacted with human immunodeficiency virus type 2
      strains (HIV-2 GH1 and ROD isolates) and SIVmac239 isolates. However, the
      antibody did not cross-neutralize these viral strains. Epitope mapping revealed
      that the neutralizing epitope recognized by M318T was localized at 8 residues
      between amino acids 178 and 185 (KRDKTKEY) in gp110, corresponding to the V2
      region of human immunodeficiency virus type 1 (HIV-1). Because some antibodies
      against the V2 region of HIV-1 reportedly neutralize virus infection by
      interfering with CD4-gp120 interaction, we tested the activity of M318T against
      the binding of CD4-gp110. However, M318T did not inhibit CD4-gp110 interaction,
      suggesting the involvement of another unknown mechanism of M318T-mediated
      neutralization. In analogy with the V2 region of HIV-1, the V2 region of SIV
      contains a type specific neutralizing epitope recognized by M318T. Although some
      amino acid sequence in the epitope was conserved for the isolates of SIV and HIV
      2 and there was cross-reactivity of the antibody against the strains,
      neutralization by M318T was associated with a single amino acid (182 T) in the
      epitope.

PMID- 7632465
TI  - Production of a human anti-CD4 monoclonal antibody with antiidiotype to anti-HIV
      type 1 glycoprotein 120.
AB  - Human anti-CD4 IgG antibodies from 3 HIV-1-infected patients were affinity
      purified and shown to inhibit HIV-1 binding and infection of HBP-T cells.
      Lymphocytes from patient A, whose anti-CD4 inhibited HIV-1 binding by 68% and
      infection by 72%, were cultured and transformed with EBV. A human monoclonal
      antiidiotype antibody against anti-HIV-1 gp120 (2B) was produced, which inhibited
      infection of HBP-T cells by 68% at 1 microgram/ml. Mice were immunized with 2B to
      determine whether this anti-CD4 could be an internal image antiidiotype against
      anti-HIV-1 gp 120 (Ab1). Two mice produced antisera reactive with rgp120 on
      ELISA, whereas immunization with normal IgG produced minimal reactivity compared
      to unreactive normal mouse sera. However, immunoblot competition studies in which
      affinity-purified anti-HIV-1 gp120 (Ab1) bound to the gp120 band on
      nitrocellulose strips in the presence of 2B demonstrated enhancement of signal
      (i.e., binding of Ab2 to Ab1), rather than inhibition of Ab1 binding. Thus 2B is
      not an internal image of the paratope of anti-HIV-1 gp120 but yet it is capable
      of inducing an antibody against rgp120. This indicates that the anti-CD4 (Ab2)
      does bind to the binding site of Ab1, but not as a complete internal image. These
      data indicate the production of a human monoclonal antiidiotype antibody that
      inhibits binding of HIV-1 to CD4 and induces the production of antibody against
      HIV-1 gp120, without being an internal image antiidiotype (Ab2 beta).

PMID- 7632466
TI  - In vivo administration of CD4-specific monoclonal antibody: effect on provirus
      load in rhesus monkeys chronically infected with the simian immunodeficiency
      virus of macaques.
AB  - Since monoclonal antibodies (MAb) specific for CD4 are potent inhibitors of HIV
      and SIV replication in vitro, we explored their potential usefulness in vivo as
      an AIDS therapy. The anti-CD4 MAb 5A8 binds to domain 2 of the CD4 molecule and
      inhibits virus replication and virus-induced cell fusion at a postvirus binding
      step. Administration of this MAb to normal rhesus monkeys coats all circulating
      and lymph node CD4 cells and induces neither CD4 cell clearance nor measurable
      immunosuppression. In the present study, monkeys chronically infected with the
      simian immunodeficiency virus of macaques (SIVmac) had stable levels of SIVmac
      provirus in PBMC prior to treatment as measured by a quantitative polymerase
      chain reaction technique. Six infected monkeys treated with anti-CD4 MAb
      demonstrated a significant decrease in SIVmac provirus level after 9 days. Of
      these monkeys, 3 had > 800 CD4 cells/microliter and developed strong antimouse Ig
      responses that prevented further treatment. The remaining 3 monkeys had < 800 CD4
      cell/microliter and failed to develop antimouse Ig antibody responses. When
      treatment was continued for 12-21 days in these monkeys, a sustained or further
      decrease in SIVmac provirus load occurred over the extended treatment period.
      Four monkeys that received a control MAb of irrelevant specificity for 9-22 days
      showed either no significant change or a transient increase in SIVmac provirus.
      Thus, the passive administration of anti-CD4 MAb may exert a specific antiviral
      effect in controlling immunodeficiency virus infection in vivo.

PMID- 7632467
TI  - An expanded search for human infection with simian type D retrovirus.

PMID- 7632468
TI  - Analysis of a feline immunodeficiency virus provirus reveals patterns of gene
      sequence conservation distinct from human immunodeficiency virus type 1.

PMID- 7632469
TI  - Student debt.

PMID- 7632470
TI  - Sticks and stones may hurt ... but words also hurt.

PMID- 7632471
TI  - Mercury levels in dentists of reproductive age.

PMID- 7632472
TI  - HIV awareness and needlestick injuries.

PMID- 7632473
TI  - HIV awareness and needlestick injuries.

PMID- 7632474
TI  - Immunisation of Brazilian dentists against hepatitis B.

PMID- 7632475
TI  - Impacted third molars.

PMID- 7632476
TI  - Orthodontics and infective endocarditis prophylaxis.

PMID- 7632477
TI  - Clinically essential.

PMID- 7632478
TI  - Hepatitis B vaccination: knowledge among clinical dental staff and students in
      Dundee.

PMID- 7632479
TI  - Inadequately trained dental surgeons.

PMID- 7632480
TI  - Long cone v short cone in radiology.

PMID- 7632481
TI  - The qualitative assessment of complete dentures produced by commercial dental
      laboratories.
AB  - Comprehensive criteria and simple methods of assessment have been developed for
      the evaluation of complete dentures supplied by commercial dental laboratories.
      One hundred laboratories in England and Wales were selected by random sampling. A
      single identical complete denture case was sent from general practice addresses
      to each of the selected laboratories and each of the laboratory stages evaluated
      according to specific criteria. This paper is concerned only with the evaluation
      of the finished dentures. Half of the cases were treated as NHS cases and half as
      'private' cases. The private cases were further subdivided into those where
      details were left to the laboratory and those where detailed instructions were
      given for all stages of denture construction. Wide variations were found in both
      the quality and cost of complete denture laboratory work. Evaluation of some key
      features of finished dentures suggests that the quality of work was superior for
      the private cases in which detailed instructions were given to the laboratory.
      Even for the private (specified) cases, however, important faults were found in a
      number of cases.

PMID- 7632482
TI  - The dentine-bonded ceramic crown: an ideal restoration?
AB  - The principles used in the bonding of porcelain veneers may also be applied to
      full-coverage restorations, with such crowns luted using resin-based materials.
      For these full coverage restorations, dentine bonding agents, preferably of low
      film thickness, may be used to treat areas of exposed dentine prior to placement.
      These 'dentine-bonded' all-ceramic crowns may exhibit many favourable
      characteristics, including those of good aesthetics and peripheral blend with
      gingival tissues and the potential for placement on conservative preparations
      which may minimise the risk of pulpal damage. Indications include cases in which
      conventional crowns require replacement, those in which minimal preparation
      techniques are appropriate, and those in which there has been tooth surface loss.
      Contraindications include subgingival margins, extreme occlusal interferences and
      insufficient tooth substance for bonding. However, the longevity of these
      restorations is, as yet, unknown, in the absence of long-term clinical data.

PMID- 7632483
TI  - Chronic sinusitis and zinc-containing endodontic obturating pastes.
AB  - Several researchers have reported a link between the development of a solitary
      antral aspergillus sinusitis and the presence of zinc-containing root canal
      obturating paste within the antrum. If diagnosed correctly, it is generally
      accepted that this type of sinusitis can be treated effectively using surgical
      techniques alone. However, previous reports have shown that this is not always
      the case and may result in prolonged and inappropriate treatment of the
      condition. It is hoped that the reported case and literature review will assist
      both dental and medical practitioners in identifying affected patients and in the
      subsequent instigation of correct treatment regimes.

PMID- 7632484
TI  - Abducent nerve palsy following dental local analgesia.
AB  - A case of temporary abducent nerve palsy, following posterior superior alveolar
      nerve block during removal of an upper third molar tooth is presented. The
      relevant anatomy and other causes of sixth nerve palsy are considered, together
      with guidelines for the management of such an occurrence.

PMID- 7632485
TI  - The patient's view of minor oral surgery in dental practice.
AB  - A recent audit of patients who underwent minor oral surgery within their own
      general dental practice confirms that treatment performed in this environment can
      have a high level of patient satisfaction. This article reports the results of
      the audit and explores the reasons why the patients chose to receive treatment in
      this way.

PMID- 7632486
TI  - Personal experiences as a volunteer dentist in Bosnia.
AB  - 'Tasovcici Refugee Camp, Capljina, Bosnia-Herzegovina.' So read our luggage
      labels as Ruth Bardsley (a dental nurse, whom I had met for only an hour some
      weeks previously) and I set out on November 2, 1994 on our journey from
      Manchester via London, Zagreb and Split. We were not quite sure what to expect,
      but we knew it was going to be one of the most interesting, unusual and
      stimulating experiences of our lives.

PMID- 7632487
TI  - Trials and tabulations.

PMID- 7632488
TI  - A multicenter, multiple dose, open label study of the initiation of sustained
      release morphine sulfate (SRMS) in chronic pain.

PMID- 7632489
TI  - Hospice and managed care: the new frontier.

PMID- 7632490
TI  - Characteristics of hospice programs, directors, and selected staff in one western
      state.
AB  - This article presents results from a study of all hospice programs in one western
      state conducted in 1992. Personal interviews and questionnaires were utilized to
      collect data about hospice programs, hospice directors, hospice nurses, social
      workers, and chaplains. Hospice programs were identified by type, affiliation,
      size, and Medicare certification status. Eighty-seven percent of hospice
      directors in the state were female, and nurses were the directors of 58 percent
      of the state's hospice programs. Approximately half of the hospice nurses, social
      workers, and chaplains, and 42 percent of the directors had no prior hospice
      experience before assuming their present positions.

PMID- 7632491
TI  - Antidepressants in hospice care.

PMID- 7632492
TI  - Quandary at the crossroads: paternalism versus advocacy surrounding end-of
      treatment decisions.
AB  - The moral and ethical basis for promoting the patient as ultimate decision-maker
      regarding his or her treatment plan is advanced. The practice implications of
      differing educational and historical backgrounds of physicians and nurses is
      addressed. Paternalism and maternalism are examined. These traditional roles are
      contrasted with the emerging provider role as patient advocate. Recommendations
      are suggested for improved physician/ nurse/patient interaction in the resolution
      of ethical dilemmas in a highly complex health care arena.

PMID- 7632493
TI  - "The art of dying in America" and "patient refusal of nutrition and hydration:
      walking the ever-finer line".

PMID- 7632494
TI  - The effect of intravenous fluid infusion on blood and urine parameters of
      hydration and on state of consciousness in terminal cancer patients.

PMID- 7632495
TI  - Citizen Ambassador Program of People to People International's hospice delegation
      to Russia and Poland.

PMID- 7632496
TI  - The Russian way of hospice.

PMID- 7632497
TI  - [The chronically painful hand].
AB  - The usual concept of pain, constituting a warning signal corresponding to an
      identifiable peripheral lesion, is very different from that of chronic pain, a
      real pathological syndrome with a dual aspect, an organic component and a
      psychological component, with no obvious relationship to the original cause. The
      authors distinguish pain due to excessive nociception, which can be cured by
      treatment of the cause, from disafferentation pain due to a defect of
      transmission of nerve impulses to processing centres and which is refractory to
      surgical treatment. The approach to pain must be multidisciplinary: surgery,
      drugs, percutaneous neurostimulation, physiotherapy and psychotherapeutic
      management ensure a "therapeutic alliance" in difficult chronic pain patients.

PMID- 7632498
TI  - [Long-term results of proximal interphalangeal resection-arthroplasty using the
      Swanson silastic implant].
AB  - 238 PIP joint arthroplasties with "Silastic" implant were performed between 1969
      and 1990. Their results were evaluated after 12 to 24 months. We reviewed 25
      patients operated between 1971 and 1988 with a follow-up of 4 to 23 years. The
      results are evaluated in terms of joint mobility, pain, stability, strength,
      radiological appearance and patient satisfaction. These results are identical to
      those observed at short follow-up indicating the absence of any significant
      deterioration. The result obtained at 12 months postoperatively will therefore be
      maintained at 12 years. Our conclusion is that unless an ideal arthroplasty with
      joint prosthesis can be shown to be effective, joint resection-arthroplasty
      remains a valuable and durable solution for the treatment of PIP joint stiffness.

PMID- 7632499
TI  - [Tendinitis of the long palmar muscle tendon. Physiopathology and results of
      surgical treatment. Apropos of 28 cases].
AB  - The results of a 27 cases of flexor carpi radialis tenosynovitis, operated
      between 1984 and 1992 and followed for an average of 30 months, are reported.
      This study confirms the female predominance of this disease (25 women for two
      men) and its development mainly after the age of fifty. Pain along the course of
      the tendon is a constant sign, frequently associated with dysaesthesia in the
      territory of the palmaris brevis branch of the median nerve as well as synovial
      swelling. Surgery was indicated because of failure of apparently correctly
      conducted medical treatment. The technique consists of synovectomy and resection
      of all sources of irritation of the tendon in its sheath. The development of
      trapezium or scaphoid osteophytes is a common cause of irritation. The functional
      result obtained was good or excellent in 22 cases. This study confirmed the
      existence of a close relationship between the development of flexor carpi
      radialis tenosynovitis and the presence of external osteoarthritis of the carpus,
      as this combination of lesions was observed in 20 of the 27 cases. Carpal
      osteoarthritic lesions appear to be responsible for the great majority of cases
      of flexor carpi radialis tendinitis observed in women over the age of 50 years.
      Following failure of medical treatment, surgical treatment is effective provided
      it includes treatment of any osteoarthritic lesions present.

PMID- 7632500
TI  - [Osteosynthesis using intra-focal pins of anteriorly dislocated fractures of the
      inferior radial epiphysis].
AB  - The authors describe two anterior approaches to intra-focal pinning of distal
      radius fractures, with anterior tilt, Smith type and anterior margin type. They
      demonstrate that this fixation mode is as reliable as anterior plate
      osteosynthesis, with less anatomic cost. It allows immediate mobilization and
      affords good functional results. Performed with regular K. Wire or better with
      "Arum" Pins, this procedure was used in ten Smith's fractures, six anterior
      margin fractures, one two-margins fractures, and twelve multi-fragment fractures.
      Anterior pins are also used when excessive anterior reduction is feared in
      Colle's fractures. Secondary displacements are rare, except radius shortening
      which is possible with all types of fracture and treatment. As cast is
      prohibited, early rehabilitation provides good and excellent functional results.
      Complications are exceptional, occurring at the beginning of the authors'
      experience. Thanks to some precaution, such as the "open approach" and protecting
      the pin ends, this technique is simple, reliable, economic and effective.

PMID- 7632501
TI  - [An unusual variation of luxation of the wrist: external vertical luxation.
      Apropos of a case. Review of the literature].
AB  - A case of lateral dislocation of the carpal scaphoid associated with a fracture
      of the triquetral and carpo-metacarpal dislocation of the ring and little finger
      is described. A thorough search of the literature failed to reveal any previous
      report of this combination of injuries. The dislocation was reduced by
      manipulation, but the scapholunate ligament required surgical repair. The results
      after two year was good.

PMID- 7632502
TI  - [A simple and efficient pin guide].
AB  - The authors propose the use of the metallic trocar used for venous catheter
      introduction as a pin guide and protector. These trocars are available in several
      internal diameters, allowing the use of 8/10 mm to 15/10 mm Kirschner pins. This
      technique has the following advantages: easy guiding of the pins and protection
      of subcutaneous neurovascular structures. The disadvantages are related to
      overheating and its consequences due to metal-on-metal friction.

PMID- 7632503
TI  - [A reverse vascular autograft finger island flap. A review of 15 cases and of the
      literature].
AB  - The authors discuss the indications for homodigital island flap with a reverse
      vascular pedicle. This flap is based on the anastomoses between the radial and
      ulnar digital arteries. These anastomotic branches lie between the posterior wall
      of the tendon sheath and the periosteum to form an arch and are named the
      "digitopalmar arches". The vascularization of the reverse homodigital island flap
      is derived by using the middle transverse palmar arch. This flap was performed
      successfully in 14 patients involving 15 fingers to resurface amputation of the
      distal phalanx. In 6 cases the flap was used as an "artery" flap, and in 9 cases
      as a "sensitive" homodigital island flap. The pedicle in these cases was
      neurovascular also containing the digital nerve. The sensitivity of the flap was
      obtained by neurorraphy between the transposed digital nerve of the flap and the
      receiving digital nerve of the recipient finger. This technique achieves cover of
      the tactile pad in one operative stage and provides well vascularized skin
      allowing early mobilization. Sensation of the flap can be restored rapidly when
      neurorraphy of the transposed digital nerve is performed.

PMID- 7632504
TI  - [Somesthetic evoked potentials and serial motor evoked potentials in the study of
      proximal peripheral nerve conduction. Apropos of 7 cases].
AB  - The study of proximal motor and sensory nerve conduction in the thoracic outlet
      syndrome is still difficult and laborious in 1994. However, these conductions can
      be measured at different levels by means of somaesthetic evoked potentials and
      motor evoked potentials, when one takes the time to perform them. The study in
      normal subjects demonstrates that the proximal sensory and motor conduction
      delays are approximately 3.2 ms and are therefore comparable to that of the
      median nerve at the wrist. The study of 7 cases related to various diseases shows
      that these techniques, performed after electromyogram of both upper limbs, an
      essential prerequisite to their interpretation, are able to clearly demonstrate
      abnormalities of proximal conduction in patients suffering from of a scalene
      syndrome, a cervical epiduritis, radiation plexopathy, hereditary sensible to
      pressure neuropathy, motor neuropathy with persistent multifocal conduction
      blocks, or, on the contrary, may confirm the normality of conduction, for example
      in anterior horn disease.

PMID- 7632506
TI  - New equipment--why? How?

PMID- 7632505
TI  - Seniors and self-care hemodialysis.
AB  - The expansion of a central renal unit's facilities by the establishment of a self
      care satellite unit provided an opportunity for significant savings in travel
      time for patients. It was decided to offer self-care training to a number of
      older patients who might not otherwise have been considered for this modality. An
      effective training program was developed for these older patients, designed to
      meet their specific needs. They were able to learn at their own pace, thus
      reducing stress and the fear of failure.

PMID- 7632507
TI  - Evaluation and management of bilateral renal artery stenosis in children: a case
      series and review.
AB  - This report describes the clinical course, diagnostic evaluation and management
      of six children with bilateral renal artery stenosis (RAS) and concurrent
      narrowing of the abdominal aorta. Except for one child with active arteritis, the
      others were asymptomatic. There were no clinical or laboratory features
      suggesting the etiology of hypertension in four of six patients, and diagnostic
      procedures, including Doppler duplex ultrasound and captopril scintigraphy, were
      unreliable in screening for such hypertension. Abdominal aortography and
      selective renal angiography confirmed the diagnosis of bilateral RAS and
      associated anatomical alterations of the aorta and its branches. The hypertension
      was severe and minimally responsive to antihypertensive agents. It was cured or
      improved after percutaneous transluminal angioplasty (PTA) of three vessels in
      two children with mid-vessel stenoses, while hypertension persisted after PTA of
      two mid-vessel stenoses in a third child and one vessel with ostium stenosis in a
      fourth child. Autotransplantation of seven kidneys in four children resulted in
      cure of significant improvement of the hypertension. Renal function was preserved
      in all children during a mean follow-up time of 41 months. Based on illustrative
      data from these six children, as well as information from a review of the
      literature, this report discusses the key diagnostic issues and stresses the
      potential advantages of renal autotransplantation in selected children with this
      disorder.

PMID- 7632508
TI  - Response of type I membranoproliferative glomerulonephritis to pulse
      methylprednisolone and alternate-day prednisone therapy.
AB  - Sixteen children with biopsy-confirmed type I membranoproliferative
      glomerulonephritis (MPGN) were treated with six alternate-day intravenous pulses
      of methylprednisolone followed by single-dose alternate-day prednisone for 12-66
      months (mean 37 months). The average length of follow-up was 52 months (range 12
      127 months). Compared with pretreatment values, the frequency of hematuria (13/16
      vs. 8/16, P < 0.05) and the levels of serum albumin (2.66 +/- 0.69 vs. 3.76 +/-
      0.39 g/dl, P < 0.001), creatinine clearance (97 +/- 37 vs. 129 +/- 26 ml/min/1.73
      m2, P < 0.001), and proteinuria (5.2 +/- 5.1 vs. 1.0 +/- 0.8 g/day, P < 0.001)
      were significantly improved after 3 months of therapy. Improvement has persisted
      through the end of the follow-up period. Repeat kidney biopsies showed a
      significant reduction in acute changes but an increase in chronic changes.
      Thirteen patients have been off therapy from 1 to 74 months (mean 20.8 months).
      Nine have a normal urinalysis, creatinine clearance, and protein excretion. The
      remainder have normal renal function but proteinuria ranging from 3.2 to 4.3
      g/day. The data support the evidence of other investigators that corticosteroid
      therapy is beneficial in type I MPGN and suggest that initiation with pulse
      methylprednisolone may promote early stabilization of the disease.

PMID- 7632509
TI  - Idiopathic membranoproliferative glomerulonephritis in Japanese children.
AB  - The course of idiopathic membranoproliferative glomerulonephritis (MPGN) in 41
      Japanese children (21 boys, 20 girls) is reported. The mean follow-up period was
      8 years, 9 months; 29 children with MPGN (71%) were identified by school urinary
      screening; 32 patients had type I MPGN, 2 type II and 7 type III; 10 patients
      were treated with multiple low-dose cocktail therapy (MLD), 8 with MLD followed
      by high-dose alternate-day (ALD) prednisolone and 21 with high-dose ALD
      prednisolone alone. In 1 patient, MPGN progressed to end-stage renal failure. The
      serum creatinine level in all of the remaining 40 patients was < or = 1.3 mg/dl
      at the last follow-up. Urinalysis was normal in 24 (59%). Of the 17 patients who
      still had urinary abnormalities, 4 had nephrotic syndrome. The incidence of
      remission of urinary abnormalities was highest in the patients treated with high
      dose ALD prednisolone. Rebiopsy was performed in 33 patients, and revealed slight
      histological improvement in 11 (33%) patients, moderate improvement in 8 (24%),
      marked improvement in 5 (15%) and deterioration or no improvement in 9 patients
      (27%). Relatively few side effects of treatment were observed. The superior
      outcome of the MPGN patients in this compared with other studies may be the
      result of earlier detection and treatment.

PMID- 7632510
TI  - Vitamin D metabolites in childhood nephrotic syndrome.
AB  - We measured serum levels of total and ionised calcium, phosphate, intact
      parathyroid hormone, 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D
      [1,25(OH)2D] and the vitamin D binding protein (DBP) in 14 children with
      idiopathic nephrotic syndrome and 10 healthy, age-matched controls. In all
      nephrotics serum DBP levels were below the normal range. Serum 25(OH)D was below
      7 ng/ml in 10 of 14 nephrotic children and in the low normal range in the
      remaining 4 patients. The average serum 1,25(OH)2D levels were lower in the
      nephrotic patients than in the controls. However, free 1,25(OH)2D levels were
      normal in the nephrotic patients. Both serum 25(OH)D and 1,25(OH)2D correlated
      positively with the concentration of DBP. There was a significant negative
      correlation between serum DBP levels and the urinary protein excretion and a
      significant positive correlation between the urinary excretions of DBP and
      albumin. From this study it can be concluded that the nephrotic child is capable
      of maintaining appropriate serum concentrations of free calcitriol despite
      important urinary losses of both substrate and bound calcitriol.

PMID- 7632511
TI  - Ambulatory blood pressure monitoring in healthy schoolchildren.
AB  - Ambulatory blood pressure monitoring (ABPM) was performed in 564 healthy
      schoolchildren during normal circadian activities. The data of two cohorts (155
      boys and 139 girls aged 9-13 years and 184 boys and 168 girls with a body height
      between 120 and 155 cm) are presented. From the age of 9 to 13 years the mean 24
      h systolic/diastolic blood pressure (SBP/DBP) increases from 107 +/- 9/66 +/- 7
      mmHg to 115 +/- 13/68 +/- 9 mmHg in boys and from 104 +/- 5/64 +/- 6 mmHg to 109
      +/- 8/65 +/- 9 mmHg in girls. When related to body height the values rise from
      105 +/- 6/64 +/- 6 mmHg at 120 cm to 113 +/- 8/67 +/- 7 mmHg at 155 cm in boys
      and from 100 +/- 7/65 +/- 7 mmHg to 112 +/- 9/66 +/- 9 mmHg in girls. In
      comparison with the causal blood pressure data obtained from European studies,
      the presented ABPM values (daytime BP) are higher throughout, which may be
      explained by the increased activity during daytime with ABPM. There is a mean
      difference of 4.4 mmHg in boys and of 3.0 mmHg in girls for SBP and of 10.8 mmHg
      in boys and of 9.0 mmHg in girls for DBP when related to age. In relation to body
      height, there is a mean difference of 4.4 mmHg in boys and of 3.5 mmHg in girls
      for SBP and of 10.9 mmHg in boys and of 10.5 mmHg in girls for DBP. We conclude
      that standards derived from causal blood pressure measurements should not be used
      for the evaluation of ABPM data.

PMID- 7632512
TI  - Diabetes-like renal glomerular disease in Fanconi-Bickel syndrome.
AB  - The Fanconi-Bickel syndrome is a rare inherited disorder of metabolism
      characterized by hepatic glyconeogenesis, galactose intolerance, renal Fanconi
      syndrome with nephromegaly, and glycogen accumulation in proximal renal tubular
      cells. An 8-year-old patient with this disease and severe rickets due to
      medically resistant hypophosphatemia was found to have the previously
      unrecognized complication of renal glomerular hyperfiltration, microalbuminuria,
      and diffuse glomerular mesangial expansion. Similar to patients with glucose-6
      phosphatase deficiency, the glomerular disease in this patient resembles
      incipient diabetic nephropathy. The Fanconi syndrome may be due to the defective
      transport of glucose at the proximal tubular basolateral membrane, which results
      in accumulation of glucose and secondarily glycogen within tubular cells. Since
      the metabolic defect, as evidenced by glycogen accumulation, selectively involves
      proximal renal tubular cells in the kidney of patients with Fanconi-Bickel
      syndrome and glucose-6-phosphatase deficiency, the abnormalities in renal
      glomerular hemodynamics and mesangial construct in these rare diseases are likely
      due to renal tubular factors, if the mechanism originates in the kidney. A
      delineation of these phenomena may further our understanding of the pathogenesis
      of diabetic nephropathy.

PMID- 7632513
TI  - Serum proteins in the haemolytic uraemic syndrome.
AB  - In 122 patients with the haemolytic uraemic syndrome (HUS), serum proteins were
      analysed in the acute phase of the disease (n = 122) and 6 weeks (n = 57) and 6
      months (n = 84) later. Total serum protein levels were significantly lower on
      admission than 6 weeks and 6 months later (P < 0.0001). The same was true for
      median values of serum albumin (P < 0.0001), alpha 2-globulins (P < 0.0001) and
      gamma-globulins (P < 0.001). There was no difference in beta-globulins, whereas
      the alpha 1-globulins were significantly higher in the acute phase (P < 0.0001).
      There was a significant positive correlation between age and total protein and
      gamma-globulin levels. Serum total protein and albumin levels displayed a
      significant positive correlation with serum sodium levels and a significant
      negative correlation with urinary protein excretion. Patients with oligoanuria
      had significantly lower serum albumin and significantly higher alpha 1-globulin
      levels than those with preserved urine production. Marked differences were
      observed between patients with (D+) and patients without (D-) prodromal
      diarrhoea. In D(-) HUS, only albumin and total protein levels were lower on
      admission, but to a lesser degree than in D(+) HUS. Serum alpha 1-globulin levels
      were significantly higher and alpha 2-globulin levels significantly lower in D(+)
      HUS than D(-) HUS. In the D(+) subgroup of patients, by far the largest, there
      was a significant positive correlation between serum albumin and total protein on
      the one hand and the duration of the prodrome on the other.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7632514
TI  - Precise determination of the absorptive component of urinary calcium excretion
      using stable isotopes.
AB  - Some patients with hypercalciuria are thought to have enhanced enteric calcium
      absorption, with a major component of recent diet contributing to urinary
      calcium. This mechanism has been difficult to test with the usual calcium loading
      procedures. We employed dual stable calcium isotope tracers to quantitate the
      components of urinary calcium excretion in 38 healthy female children. The mean
      urinary calcium excretion in these girls was 2.4 mg/kg per day. The contribution
      of recent diet to this total was a mean of 0.2 mg/kg per day. The maximum dietary
      contribution to urinary calcium excretion was 0.86 mg/kg per day. Recent diet
      contributes a mean of 8% to total dietary calcium excretion. This novel method
      permits precise quantitation of the contributions of recent diet and tissue
      stores to urinary calcium excretion. In these healthy girls, the fraction of
      urinary calcium derived from diet is trivial.

PMID- 7632515
TI  - Validity of measurements of calcium absorption.

PMID- 7632516
TI  - Urinary excretion of retinol-binding protein in healthy children and adolescents.
AB  - Retinol-binding protein (RBP) is a marker of tubular reabsorption in the kidneys.
      The aim of our study was to investigate urinary RBP excretion in healthy children
      to obtain reference values related to age and pubertal stage. Overnight samples
      from 143 subjects (73 girls, 70 boys) aged 10-18 years were investigated. RBP was
      quantified by a solid-phase sandwich enzyme immunoassay. Both the RBP excretion
      rate and the RBP/creatinine ratio (RBP/Cr) showed a skewed distribution. The
      medians and the 5th-95th percentiles were 38 ng/min (15-127) and 9
      micrograms/mmol (4-23), respectively. The RBP excretion rate and RBP/Cr ratio
      were similar in both sexes, and linear multiple regression analysis showed no
      association with age or pubertal stage, although a weak relationship (r = 0.27)
      was found between RBP excretion rate and age in boys and RBP/Cr ratio and age (r
      = -0.28) in girls by simple correlation analysis. The correlation between RBP
      excretion rate and RBP/Cr ratio was 0.76; the RBP excretion rate and RBP/Cr ratio
      measured on 2 consecutive days, showed a correlation coefficient of 0.84 and
      0.88, respectively. We conclude that overnight RBP excretion in children over 10
      years shows a low day-to-day variation and, in practical terms, is independent of
      age, gender and pubertal stage.

PMID- 7632517
TI  - What causes the electrocardiographic changes in hyperkalemia?

PMID- 7632519
TI  - What causes the electrocardiographic changes in hypokalemia?

PMID- 7632520
TI  - Are there any long-term risks to levamisole therapy?

PMID- 7632518
TI  - Deleterious effects of inhibition of the renin-angiotensin system in neonatal
      rats.
AB  - The angiotensin I converting enzyme inhibitor (ACEI) perindopril (2 mg/kg body
      weight), the peripheral vasodilator dihydralazine (DHL) (25 mg/kg body weight) or
      distilled water was given daily from birth to day 14 to neonatal rats. Blood
      pressure, plasma creatinine, plasma renin activity (PRA), substrate (PRS) and
      concentration (PRC) and renin content of kidney tissue sections were evaluated on
      days 14 and 28. By day 14, a high mortality in the ACEI group was observed. ACEI,
      but not DHL, led to a significant fall (P < 0.01) in blood pressure, 57 +/- 11
      versus 89 +/- 25 in the DHL group and 103 +/- 24 mmHg in controls, and to a
      dramatic increase in plasma creatinine. PRA and PRS were undetectable in ACEI
      treated rats; in contrast, PRC and renal staining with anti-renin antibody were
      significantly increased in ACEI rats. On day 28, the blood pressure was normal in
      all groups and plasma creatinine returned to the normal range in ACEI rats. PRA,
      PRS and PRC were not significantly different in the ACEI group and controls.
      These results suggest that the renin-angiotensin system (RAS) plays a major
      postnatal role in the neonatal rat. Inhibition of the RAS during the first 2
      weeks of life leads to high mortality, severe hypotension, reversible renal
      failure and a defect in circulating angiotensinogen.

PMID- 7632521
TI  - The effect of lymphocytes from renal transplant patients on glomerular basement
      membrane sulfate uptake.
AB  - We have studied the effect of peripheral blood mononuclear cells (PBMC) from
      renal transplant patients on 35sulfate uptake by rat glomerular basement membrane
      (GBM). Nine patients were included in the study; six were studied during an
      episode of acute allograft rejection and seven while not undergoing acute
      rejection. The sulfate uptake index, calculated as the ratio between uptake by
      GBM from rat glomeruli cocultured with PBMC and 35sulfate incorporation by GBM
      from glomeruli cultured alone, was significantly higher when glomeruli were
      cocultured with PBMC from patients undergoing an acute rejection (3.26 +/- 1.18,
      mean +/- SEM) than it when glomeruli were cocultured with PBMC from nonrejecting
      transplant patients not showing proteinuria (0.81 +/- 0.11) (P = 0.0053). After
      reversing the acute allograft rejection with resolution of proteinuria, the
      sulfate uptake index returned to normal in four of five patients. The fifth
      patient had persistent nephrotic syndrome and his sulfate uptake index remained
      elevated. These findings are similar to those observed in idiopathic minimal
      lesion nephrotic syndrome patients in relapse. Because the GBM sulfated compounds
      may play a role in glomerular permeability to plasma proteins, by acting on these
      compounds PBMC may be a common mechanism for proteinuria.

PMID- 7632522
TI  - Acute post-streptococcal glomerulonephritis in a renal allograft.
AB  - We report a 12-year-old male with acute post-streptococcal glomerulonephritis
      (APSGN) occurring 1 year after a cadaveric renal transplant. Although recurrent
      and de novo renal transplant glomerulonephritides have been well described in
      large series of adult and pediatric renal transplant recipients, post-infectious
      glomerulonephritis has been rarely reported, and APSGN has never been reported in
      either adult or pediatric transplant series. We speculate on the reasons for the
      lack of occurrence of APSGN in renal transplant recipients.

PMID- 7632523
TI  - "Low-dose" growth hormone therapy during peritoneal dialysis or following renal
      transplantation.
AB  - The minimal effective dose of growth hormone (GH) to promote growth in children
      on dialysis or following renal transplantation remains unsettled. In order to
      study the issue, "low-dose" GH was administered to children with end-stage renal
      disease (ESRD) receiving chronic automated peritoneal dialysis (APD, n = 6, 4
      males, 2 females) or following renal transplantation (T, n = 9, 8 males, 1
      female). No APD patient was GH deficient, while 1 T patient (no. 2) had data
      consistent with GH deficiency, although he was obese (body mass index = 34
      kg/m2). The mean dose of GH after 6 and 12 months of treatment was 0.16 +/- 0.02
      and 0.22 +/- 0.07 versus 0.16 +/- 0.03 and 0.27 +/- 0.21 mg/kg per week for APD
      and T patients, respectively. When analyzing all patients, there were no
      significant differences before or after 6 and 12 months of GH therapy within or
      between the two groups, in terms of height velocity, bone age, renal function (in
      the T group) and height Z-scores (Z-Ht). However, the height velocity Z-score (Z
      HV) increased significantly at 6 and 12 months compared with baseline in the APD
      patients only (P < 0.05). When the 2 T patients with the most impaired renal
      function were excluded from the analysis, Z-HV also increased significantly in
      the T patients after 12 months of GH (P < 0.02). We conclude that following "low
      dose" GH therapy, children with ESRD treated with APD or T have similar increases
      in HV, allowing maintenance of Z-Ht but not "catch-up" growth.

PMID- 7632524
TI  - Evoked potentials in children with chronic renal failure, treated conservatively
      or by continuous ambulatory peritoneal dialysis.
AB  - Children with chronic renal failure (CRF) show developmental, intellectual and
      motor disturbances. It is questionable if an early start of renal replacement
      therapy may prevent or delay these disturbances. We studied the neurological and
      intellectual development of children < 5 years suffering from CRF (creatinine
      clearance < 20% of normal) prospectively, over a period of 3 years. As part of
      the neurological study, brainstem auditory evoked potentials (BAEP) and
      somatosensory evoked potentials (SSEP) were recorded. Measurements were performed
      in a group of 22 children every 6 months. In 18 of these children CRF was present
      from birth. Sufficient data were available for analysis in 19 (BAEP) and 22
      (SSEP), respectively. A delay of peak I of BAEP gave indications for peripheral
      conduction disturbances, possibly due to cochlear dysfunction. Brainstem
      conduction was normal. There were no differences between the children treated
      conservatively (n = 9) and those treated with continuous ambulatory peritoneal
      dialysis (CAPD) (n = 10). In children < 2.5 years SSEP showed a delayed
      thalamocortical conduction, which was not observed in older children. This might
      indicate a delayed myelination in young children with CRF. No differences were
      found between the children treated conservatively (n = 10) and those treated with
      CAPD (n = 12).

PMID- 7632525
TI  - Dialysis delivery in children on nightly intermittent and tidal peritoneal
      dialysis.
AB  - To achieve more adequate dialysis in a shorter treatment time, seven children,
      characterized as high/high average (H/HA, 5 patients) and low/low average (L/LA,
      2 patients) transporters according to the peritoneal equilibration test, were
      treated with tidal peritoneal dialysis (TPD) for 13.7 +/- 5.7 months, after being
      treated with nightly intermittent peritoneal dialysis (NIPD) for a similar
      period. We determined the TPD prescription necessary to provide improved
      clearances compared with NIPD within the same or less treatment time. Dialysis
      flow rate was significantly higher in TPD than NIPD, due to a reduction of dwell
      time and an increase in the number of exchanges. Peritoneal and total clearances
      of urea and creatinine were higher, whereas serum creatinine and urea nitrogen
      levels were lower and treatment duration shorter during TPD than NIPD,
      notwithstanding a decrease of residual renal function. Moreover, a mean time
      averaged blood urea nitrogen level as low as 48.5 +/- 11.6 mg/dl was achieved
      during TPD. The improvement was more significant in H/HA than in L/LA patients.

PMID- 7632526
TI  - Cytokine production by peripheral blood mononuclear cells from pediatric chronic
      peritoneal dialysis patients.
AB  - Previous reports have documented impaired cytokine production by peritoneal
      macrophages in chronic peritoneal dialysis (CPD) patients. To determine if this
      observed defect was a reflection of systemic mononuclear cell dysfunction, the
      function of peripheral blood mononuclear cells obtained from pediatric patients
      on CPD was assessed after stimulation with lipopolysaccharide (LPS). Levels of
      interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) mRNA
      and protein were measured before and after stimulation with LPS. There was no
      significant difference in the response of mononuclear cells from CPD patients and
      normal controls in terms of increase in TNF-alpha mRNA [median stimulation index
      (SI) = 6.6 vs. 3.7, P = 0.35] or IL-1 beta mRNA (median SI = 6.2 vs. 6.5, P =
      1.0). There was also no significant difference between the median increase in TNF
      alpha protein secretion (median 372 pg/ml vs. 373 pg/ml, P = 0.60). These results
      suggest that systemic mononuclear cell function may be intact in CPD patients,
      and therefore this does not account for the dysfunction of peritoneal macrophages
      that has been previously reported.

PMID- 7632527
TI  - Assessment of the sensitivity of bioimpedance to volume changes in body water.
AB  - The sensitivity of whole-body electrical impedance measurements to changes in the
      volume of total body water in 12 children undergoing haemodialysis has been
      assessed. The impedance (I) of each child was measured at 20-min intervals during
      dialysis using the standard four-electrode technique to apply a constant current
      (800 microA, 50 kHz) between the wrist and ankle on the non-fistula side of the
      patient. The ultrafiltration volume (U) was also recorded. A simple electrical
      model suggests that U = aHt2 ((1/I0)-(1/I)), where I0 is the whole body impedance
      at the start of dialysis, a is a constant and Ht is patient height. No
      significant changes in I were measured on 4 patients undergoing dialysis without
      ultrafiltration, whereas in 8 patients undergoing ultrafiltration and dialysis I
      increased. Linear regression analysis and the above equation gave a mean value
      for a = 0.566 1 Ohm/cm2 (coefficient of variation = 3%), (mean r = 0.97), values
      comparable to those values obtained from isotope dilution studies. Predicted
      fluid loss in 8 patients following a single dialysis session gave a mean
      overestimate of 4.3% (limits of agreement 27.3% and -19.7%), although in 6 of the
      patients agreement was to within 6%. Changes in impedance reflect changes in
      total body water in children undergoing haemodialysis and are relatively
      insensitive to factors such as the possible differences in electrolyte levels
      between these patients.

PMID- 7632528
TI  - Use of a modified peritoneal equilibration test to optimize solute and water
      clearance.
AB  - The standard peritoneal equilibration test (PET) characterizes the peritoneal
      transport of fluid, creatinine and urea. However, the applicability of the
      standard PET may be limited in patients on cycling peritoneal dialysis due to the
      choice of 2- and 4-h sampling times which exceed the usual dwell time of most
      patients on cycling peritoneal dialysis. We have performed a modified PET on
      seven pediatric dialysis patients in an effort to optimize dwell time to achieve
      maximal clearance of solutes and fluid. When compared with the standard PET,
      values obtained for dialysate/plasma urea and dialysate/plasma creatinine with
      the modified PET are significantly different. This resulted in an increased
      estimated creatinine clearance in five of seven and increased estimated urea
      clearance in six of seven patients. The modified PET is a more appropriate method
      for evaluation of peritoneal clearances in children as well as older patients who
      may require cycling peritoneal dialysis.

PMID- 7632529
TI  - Acute renal failure in a child associated with acyclovir.
AB  - A 9-year-old boy developed acute renal failure following intravenous acyclovir
      (30 mg/kg per day) administered for 6 days to treat herpetic encephalitis.
      Physical findings and urine output were normal, except for increasing blood urea
      nitrogen (BUN), serum creatinine and mild proteinuria. Acyclovir was
      discontinued. However BUN and serum creatinine continued to increase and peaked
      on the following day at 8.6 mmol/l of urea (24 mg/dl) and 194 mumol/l (2.2
      mg/ml), respectively. Conservative treatment and hydration were carried out. The
      kidney function returned to normal within 1 week. The use of acyclovir when
      necessary in renal failure patients is discussed.

PMID- 7632530
TI  - Spurious rise in total carbon dioxide and chloride with negative anion gap after
      cystogram.
AB  - We report a case of spurious hyperchloraemia, elevated total carbon dioxide and
      negative anion gap 9 days following a voiding cystourethrogram (VCU) in a patient
      with bladder exstrophy and obstructive uropathy. We believe that the spurious
      laboratory results were due to analytical interference of the absorbed iodine
      with the method of bicarbonate and chloride measurement. The absorbed iodine was
      retained in the circulation for an extended period because of associated renal
      impairment. Our patient was also on piperacillin which might have interfered with
      iodine clearance. Physicians and laboratory pathologists should be aware of this
      effect when interpreting laboratory results of patients who have undergone a VCU
      in association with obstructive uropathy and impaired renal function.

PMID- 7632531
TI  - Ultrasonographic evaluation of bladder volume in young children.
AB  - We investigated by ultrasonography the bladders of 30 young children (26 boys, 4
      girls) without established bladder control immediately before voiding
      cystourethrography. The anterior/posterior (D), superior/inferior (H) and
      transverse dimension (W) of the bladder were determined. The small children had a
      significantly greater H value compared with D and W than older children in our
      previous study in 1993. The regression equation for D x H x W and actual bladder
      volume in 30 infants was calculated as y = 0.49 x + 3 (Eq. 1). When bladder
      volume of the 30 infants was estimated from D x H x W, the mean percentage error
      was much lower with Eq. 1 than with Eq. 2 (y = 0.68 x + 4), which had been
      determined for older children (mean +/- SD 16.8% +/- 10.7% vs. 44.7% +/- 26.2%)
      (P < 0.01). Thus, infants have a different bladder shape than older children and
      their bladder volume should be estimated using a specific formula designed for
      them.

PMID- 7632532
TI  - A case of craniomandibular dermatodysostosis associated with focal
      glomerulosclerosis.
AB  - This paper reports an isolated case of the exceedingly rare cutaneo-skeletal
      condition craniomandibular dermatodysostosis, in which focal glomerular sclerosis
      and end-stage renal failure developed and renal transplantation was required.

PMID- 7632533
TI  - Paediatric experience with acetate-free biofiltration.
AB  - We describe our preliminary experience with five children who received acetate
      free biofiltration, a modification of haemodiafiltration without buffer in the
      dialysate and simultaneous infusion of bicarbonate through a venous port.
      Adequacy of haemodialysis (HD) was achieved with 3 h treatments three times per
      week (mean Kt/v 1.35 +/- 0.29, mean protein catabolic rate (PCR) 1.4 +/- 0.3
      mg/dl). During the session, pH increased from 7.4 pre HD to 7.5 post HD. The mean
      bicarbonate infused as a 0.166 M solution averaged 235 +/- 35 mEq/h. Hypertension
      did not occur. There were no cramps, hypotension or vomiting. Bicarbonate
      requirements correlated significantly with dialyser surface area and body weight
      (r = 0.76, P < 0.001).

PMID- 7632534
TI  - Intraperitoneal erythropoietin treatment of children with chronic renal failure.
AB  - Intraperitoneal erythropoietin was given to three children on chronic peritoneal
      dialysis. Doses between 100 and 150 units/kg were given undiluted into a dry
      cavity twice weekly and left for 10-12 h before resuming dialysis. Satisfactory
      haemoglobin levels were seen over a 6-month period and there were no
      complications. Intraperitoneal administration of erythropoietin is cost-effective
      and avoids the local pain of subcutaneous injections.

PMID- 7632535
TI  - Dialytic management of childhood acute renal failure: a survey of North American
      pediatric nephrologists.
AB  - A 35-question survey was mailed to 19 pediatric nephrologists regarding dialytic
      management of acute renal failure (ARF). Fifteen surveys were returned (79%). The
      purpose of the survey was to determine which renal replacement therapies (RRT)
      are most frequently used in the management of children with ARF in North America.
      Nephrologists were also questioned about clinical factors that influence the
      decisions to initiate RRT and choice of a particular modality. Survey results
      showed that hemofiltration was the initial choice for RRT among nephrologists
      (median value 40%, range 0%-100%) more often in their patients in the past 12
      months than peritoneal dialysis (median value 30%, range 0%-85%) or hemodialysis
      (median value 20%, range 0%-50%). Factors considered most important in the
      decision to initiate dialysis include abnormalities in serum potassium, fluid
      balance, blood pressure and nutritional needs. Patient size and dialysis access
      were additional factors considered important in the choice of RRT modality.

PMID- 7632536
TI  - Potassium homeostasis and its disturbances in children.
AB  - Although only 2% of the body potassium is present in the extracellular space, its
      concentration is finely regulated by the internal balance, or distribution of
      potassium between the intracellular and extracellular compartments, and by the
      external balance, or difference between intake and output of potassium. Internal
      balance is modulated by a host of factors, including insulin, epinephrine,
      extracellular pH and plasma tonicity. Potassium output from the body is mainly
      determined by renal excretion. Renal secretion of potassium takes place
      predominantly in the principal cells of late distal and cortical collecting
      tubules, by a process involving the accumulation of potassium in the cell by the
      activity of the basolateral Na+,K(+)-ATPase and its exit through luminal
      conductive channels. The factors regulating renal potassium secretion are
      potassium intake, rate of tubular fluid flow, distal sodium delivery, acid-base
      status and aldosterone. Hypokalaemia may result from a low potassium intake,
      excessive gastrointestinal, cutaneous or renal losses and altered body
      distribution. Aetiological diagnosis and therapy are best accomplished when the
      acid-base status is assessed at the same time. Before establishing the diagnosis
      of hyperkalaemia, spurious hyperkalaemia due to haemolysis or release of
      potassium from cells during clot retraction (pseudohyperkalaemia) should be ruled
      out. Hyperkalaemia may result from exogenous or endogenous loading, decreased
      renal output and altered body distribution. Acute hyperkalaemia represents an
      emergency situation which requires immediate therapy.

PMID- 7632537
TI  - The syndrome of inappropriate secretion of antidiuretic hormone.
AB  - The physiology of the release of antidiuretic hormone (ADH) from the posterior
      pituitary is briefly reviewed. The importance of both osmolar and non-osmolar
      stimuli is emphasised. Osmolar and non-osmolar factors usually reinforce each
      other; for example, hydropenia leads to hyperosmolality and hypovolaemia, both
      promoting ADH release, while hydration has the opposite effect. In disease,
      osmolar and non-osmolar factors may become dissociated leading to baroreceptor
      mediated ADH release in the presence of hyponatraemia and hypo-osmolality.
      Examples include heart failure, glucocorticoid or thyroxine deficiency, hepatic
      cirrhosis and nephrotic syndrome with or without the superimposed effect of
      diuretics, i.e. conditions in which circulatory, and in particular effective
      arterial, volume is reduced. It is dangerous to label such conditions as
      'inappropriate' secretion of ADH since the maintenance of circulating volume is
      at least as important a physiological requirement as the defence of tonicity. The
      syndrome of inappropriate secretion of ADH (SIADH) is uncommon in childhood and
      should only be diagnosed when physiological release of ADH in response to non
      osmolar as well as osmolar factors has been excluded. Criteria for the correct
      identification of SIADH are discussed; the presence of continuing urinary sodium
      excretion in the presence of hyponatraemia and hypo-osmolality is essential to
      the diagnosis. SIADH in children is usually due to intracranial disease or
      injury. The mainstay of treatment is water restriction which reverses all the
      physiological abnormalities of the condition. Hypertonic saline is rarely
      indicated for the short-term control of neurological manifestations such as
      seizures. Drugs have little or no place in the treatment of SIADH in
      children.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7632538
TI  - Recognition and management of angiotensin converting enzyme inhibitor fetopathy.
AB  - Angiotensin converting enzyme (ACE) inhibitors are extensively used for the
      treatment of hypertension, to decrease proteinuria, and to mitigate
      hyperfiltration. These drugs now have been shown to be fetotoxic causing profound
      fetal hypotension, renal tubular dysplasia, anuria-oligohydramnios, growth
      restriction, hypocalvaria, and death when used in the second and third trimesters
      of pregnancy. We recommend that ACE inhibitors not be used in pregnancy. However,
      if a child is born with ACE inhibitor fetopathy, aggressive therapy with dialysis
      to remove the inhibitor may mitigate the profound hypotensive effects. Therapy
      will depend on the specific ACE inhibitor, and care recommendations cannot be
      generalized for the entire class of drugs as their protein binding and volume of
      distribution differ substantially.

PMID- 7632539
TI  - Contemporary approaches to renovascular hypertension in children.

PMID- 7632540
TI  - A boy with acute renal failure.

PMID- 7632541
TI  - Clinical quiz. Cerebral salt wasting syndrome.

PMID- 7632542
TI  - Obesity and genitourinary anomalies in Bardet-Biedl syndrome after renal
      transplantation.

PMID- 7632543
TI  - Successful living-related renal transplantation in an adolescent with Down
      syndrome.

PMID- 7632544
TI  - Interleukin-1 beta in intravenous albumin preparations.

PMID- 7632545
TI  - Angiotensin converting enzyme inhibitor does not reduce proteinuria in an infant
      with congenital nephrotic syndrome of the Finnish type.

PMID- 7632546
TI  - Racial incidence of hemolytic-uremic syndrome.

PMID- 7632547
TI  - Distinguishing between Bartter's syndrome and Gitelman's syndrome.

PMID- 7632548
TI  - Nocturnal enuresis.
AB  - Nocturnal enuresis is a very common pediatric problem which often has strong
      genetic roots. In the vast majority of children it resolves spontaneously, with
      time, therefore research and treatment of bedwetting cannot carry any risk to the
      child. The research on the etiology of bedwetting has been focused on sleep
      disturbances, nocturnal urine production and functional bladder capacity. So far
      it has not provided conclusive evidence of the pathophysiology of the phenomenon.
      It is possible that different factors may be predominant in different age groups.
      Although bedwetters are basically mentally healthy, several studies have shown
      that the problem may cause secondary emotional and social problems which can be
      alleviated with successful intervention. Of the treatment modalities currently
      available to the pediatrician, the most effective is the moisture alarm. Combined
      with its safety and low cost it should become the treatment of choice in most
      cases.

PMID- 7632549
TI  - Selective use of the intensive care unit following carotid endarterectomy.
AB  - The purpose of this study was to develop criteria by which selected patients can
      be observed solely on the ward following carotid endarterectomy (CEA). One
      hundred consecutive CEA patients were retrospectively reviewed. Preoperative
      medical conditions were identified, and the postanesthesia recovery room course
      was reviewed in an attempt to predict the need for intensive care unit (ICU)
      level care. Forty-four of our 100 patients developed perioperative complications
      or conditions that required some intervention. Conditions included hypertension
      in 23, hypotension in nine, arrhythmias in six, and myocardial ischemia in two.
      Complications included nonfatal cerebrovascular accident (CVA) in one, fatal CVA
      in one, and postoperative bleeding in two. Sixteen patients required ICU level
      intervention (hypertension in five, hypotension in five, arrhythmias in two,
      nonfatal CVA in one, fatal CVA in one, and postoperative bleeding in two. Fifteen
      of the 16 were identified in the recovery room. Fifty-three patients had a
      medical history of significant hypertension (42), cardiac disease (27), and/or
      recent CVA (seven). Thirty-six (68%) of these patients required perioperative
      intervention in some form; 12 (23%) required ICU level therapy. Eight of 47 (17%)
      patients without a significant medical history required intervention; only four
      (9%) required ICU level care. All eight patients were identified in recovery.
      Only 16 of 100 CEA patients required ICU level care. Fifteen of 16 were
      identified in recovery. Certain patients identified in the recovery room can be
      followed safely in a less intense and costly setting.

PMID- 7632550
TI  - Intraoperative assessment of carotid endarterectomy: a comparison of techniques.
AB  - Routine intraoperative imaging of the carotid artery following carotid
      endarterectomy can detect defects at the site of endarterectomy that may lead to
      neurologic morbidity. A number of methods have been used to evaluate the
      completed endarterectomy. In this prospective study we compared subjective
      methods of assessment (hand-held, continuous-wave Doppler imaging with audible
      interpretation of signals) and objective methods of assessment (duplex
      ultrasonography with color flow and digital subtraction arteriography) with
      respect to their ability to detect operative abnormalities. Fifty-three carotid
      endarterectomies were evaluated by means of all methods of assessment. Six
      patients had significant abnormalities in which the vessel was reopened and the
      abnormality confirmed. The sensitivity and specificity for detecting
      abnormalities for each method are, respectively: duplex ultrasonography with
      color flow, 100% and 100%; digital subtraction arteriography, 66% and 95.7%; and
      continuous-wave Doppler imaging with audible interpretation of signals, 16% and
      97.8%. There was one (1.8%) operative carotid neurologic complication during the
      postoperative period and follow-up (stroke due to vein patch rupture on
      postoperative day 2). These data suggest that an objective rather than a
      subjective method of assessing carotid endarterectomy is more useful in detecting
      operative abnormalities and that duplex ultrasonography with color flow is as
      useful as digital subtraction arteriography.

PMID- 7632551
TI  - Eversion endarterectomy of the internal carotid artery: midterm results of a new
      technique.
AB  - A new eversion endarterectomy technique was used in 65 internal carotid artery
      reconstructions in 56 patients. The original features of the technique include a
      complete oblique transection of the internal carotid artery distal to the lesion
      and eversion endarterectomy through a longitudinal incision of the common carotid
      and external carotid arteries. The mean age of the patients was 68.2 +/- 7.8
      years. Seventy-three percent of the patients had hypertension and 45.5% had
      coronary heart disease. Fifty-four percent experienced neurologic symptoms
      (transient in 36%, reversible in 6%, and permanent in 11%). Operations were
      performed under general anesthesia. An indwelling shunt was inserted whenever
      routine stump pressure was < 50 mmHg. There were no neurologic complications but
      one patient died of a compression hematoma of the neck, for a combined mortality
      and morbidity rate of 1.5%. Arteriograms were obtained from all patients on day 5
      and showed complete restoration of normal anatomy in all cases and thrombosis of
      the external carotid artery in one. During a mean follow-up of 27 +/- 4.7 months
      no strokes were observed. Follow-up duplex scans showed no hemodynamically
      significant restenoses. Eversion endarterectomy is a reliable alternative to
      other reconstruction procedures of the internal carotid artery.

PMID- 7632552
TI  - The role of intraoperative transcranial Doppler monitoring in carotid artery
      surgery.
AB  - Of 135 carotid artery reconstructions performed under general anesthesia in 127
      patients (mean age 68 years), 119 were performed with continuous intraoperative
      Doppler recording of the middle cerebral artery. This investigation was
      impossible in nine (6.7%) cases because of the absence of a visible temporal
      window, and results were deemed uninterpretable in six (4.5%) additional cases.
      The goals of this study were to test the feasibility and reliability of
      transcranial Doppler monitoring in the evaluation of intracranial perfusion and
      to determine the risk of cerebral ischemia during carotid artery clamping. The
      two outcome parameters measured were mean velocity and percentage of decreased
      flow in the middle cerebral artery during clamping. Patients were divided into
      four groups based on variations in these parameters. Groups I and IIA (low risk)
      represented 69.7% of cases, group IIB (significant risk) represented 21.9%, and
      group III (major risk) represented 8.4%. Transcranial Doppler monitoring appears
      to be a reliable means of observing middle cerebral artery flow during carotid
      surgery and in our opinion provides objective criteria for determining the need
      for an indwelling shunt. Accordingly, in this study no neurologic complications
      imputable to clamping were observed. Transcranial Doppler monitoring can also be
      used to ensure correct functioning of the shunt and to detect intraoperative
      embolic complications.

PMID- 7632553
TI  - Transesophageal echocardiography in the detection of cardiovascular sources of
      peripheral vascular embolism.
AB  - The purpose of this study was to determine the impact of transesophageal
      echocardiography (TEE) on the management of patients with peripheral vascular
      emboli. We prospectively evaluated the role of TEE in 15 patients with documented
      peripheral emboli and no evidence of occlusive peripheral vascular disease. The
      patients were divided in two groups for analysis: group 1 (n = 8) had no clinical
      evidence of heart disease and group 2 (n = 7) had clinically significant heart
      disease. TEE provided information regarding the source of embolism in four (50%)
      patients in group 1, and these findings significantly affected the management of
      all. Three patients underwent thoracic surgery to remove the source of embolism
      (aortic valve mass in one and a thrombus in the descending thoracic aorta in
      two); the other patients was treated with thrombolytic agents. TEE findings had
      high diagnostic value in all patients in group 2, but the results had a possible
      effect on clinical management in only two of these patients. TEE provides
      diagnostic information in most patients with peripheral vascular emboli and this
      information has a significant influence on management, particularly in those
      without clinically evident heart disease. TEE should be performed in all patients
      with documented peripheral embolism.

PMID- 7632554
TI  - No contralateral neutrophil (PMN) stimulation after rabbit hindlimb
      ischemia/reperfusion.
AB  - Polymorphonuclear neutrophils (PMNs) have been implicated as mediators of the
      reperfusion injury that occurs in skeletal muscle after ischemia. Our laboratory
      has previously shown that the venous effluent from rabbit hindlimbs that have
      undergone 2 or 3 hours of ischemia followed by 1 hour of reperfusion contains
      PMNs that demonstrate increased phagocytosis and chemotaxis when assayed. It was
      the purpose of this study to evaluate PMNs from the contralateral rabbit hindlimb
      utilizing the same periods of ischemia and reperfusion to determine whether this
      PMN-induced effect is localized to the ischemic limb. Rabbit hindlimbs were
      rendered ischemic by clamping the iliac and femoral arteries for 2 or 3 hours
      after ligating all pelvic collateral vessels. The ischemic limb was then allowed
      to reperfuse for 1 hour following removal of the clamps. Preischemia blood
      samples were obtained from an ear artery prior to placement of the clamps. A
      venous effluent sample was obtained to study PMNs from the contralateral limb
      after an ischemic period of either 2 or 3 hours and again after 1 hour of
      reperfusion. Phagocytosis and chemotaxis were measured and results were compared.
      No differences in phagocytosis or chemotaxis were observed in PMNs isolated from
      the contralateral limb after 2 and 3 hours of ischemia alone or ischemia followed
      by 1 hour of reperfusion in comparison with preischemia values. There were no
      significant alterations in phagocytosis or chemotaxis in PMNs obtained from the
      contralateral limb following ischemia/reperfusion.

PMID- 7632555
TI  - Behavior of cryopreserved endothelial cells in different phases: their
      application in the seeding of vascular prostheses.
AB  - Various methods of cryopreservation of human endothelial cells (EC) were studied
      to determine their viability and behavior when seeded onto vascular prostheses
      made of polytetrafluoroethylene (PTFE). Three different protocols were used: (1)
      cyropreservation of whole umbilical vein, (2) cyropreservation of freshly
      extracted umbilical EC in suspension, and (3) cryopreservation of EC derived from
      a first subculture. Fresh EC and EC from a first subculture were used as
      controls. The viability and growth of these cells in culture media were studied,
      and basal prostacyclin levels were determined. The cells were assessed
      morphologically after they were seeded onto PTFE discs. Our results showed that
      the cryopreservation method that maintained the greatest viability was that in
      which previously cultured EC were used. Basal prostacyclin levels were
      significantly different following cyropreservation. However, when these cells
      were seeded onto PTFE discs their behavior was similar to that of fresh EC.

PMID- 7632556
TI  - Chronic venous insufficiency in a Chinese population: an anatomic and functional
      study by continuous-wave Doppler and photoplethysmography.
AB  - A total of 1583 limbs in 878 patients who presented with symptoms of chronic
      venous insufficiency of the lower limbs were examined in the vascular laboratory.
      The anatomic distribution of valvular insufficiency was determined by continuous
      wave Doppler ultrasound and functional severity was determined by the venous
      refilling time (VRT) using photoplethysmography. Severity of reflux was assessed
      using a four-class grading scale (classes 0 to 3) based on clinical and VRT
      criteria. A mixed incompetence of the valves in the superficial system and the
      perforators was encountered in the majority of patients (44% in class 0 and 85%
      in class 3). Deep vein incompetence was less common and usually consisted of
      isolated proximal incompetence of the common femoral vein (up to 32% in class 3)
      or was of a mixed type (21% in class 3). Isolated distal deep vein incompetence
      was uncommon. Proximal femoral vein incompetence and superficial system
      incompetence at the saphenofemoral junction were associated with severe reflux.
      There was significant improvement in the VRT in patients with more severe reflux
      (class 2 or 3) after application of an ankle tourniquet. Symptoms of moderate to
      severe chronic venous insufficiency and ankle ulceration may be a result of long
      standing superficial system incompetence rather than deep venous disease and may
      thus be amendable to simple saphenofemoral ligation and interruption of
      perforators.

PMID- 7632557
TI  - Retrograde aortic dissection after bilateral iliac artery stenting: a case report
      and review of the literature.
AB  - We report a case of retrograde aortic dissection after bilateral iliac artery
      stenting. A 63-year-old black woman underwent aortography with balloon
      angioplasty of bilateral common iliac artery lesions and subsequent vascular
      stent placement. The patient developed an acute aortic dissection from the level
      of the aortic bifurcation to the left subclavian artery. This case is presented
      to call attention to the previously unreported complication of retrograde aortic
      dissection after bilateral iliac artery angioplasty and stent placement
      presenting as acute chest pain.

PMID- 7632558
TI  - Management options for hepatic artery aneurysms.
AB  - A 70-year-old woman underwent an elective sigmoid resection for chronic
      diverticulitis. On the third postoperative day she suddenly developed abdominal
      pain and hypotension after a coughing episode. Radiologic evaluation demonstrated
      the presence of a hemoperitoneum. A celiac arteriogram was obtained in an effort
      to determine the cause of the hemorrhage. Four aneurysms of the intrahepatic
      portions of the left and right hepatic arteries were found. These aneurysms were
      successfully treated using steel coil embolization. Surgery has traditionally
      been the "gold standard" treatment of this rare entity. Recent reports have
      demonstrated the utility of embolization in treating aneurysms of the hepatic
      arteries. This report reviews the current treatment options available in the
      management of hepatic artery aneurysms. Embolization of the aneurysms is
      recommended.

PMID- 7632559
TI  - Preoperative control of a ruptured anastomotic femoral "pseudoaneurysm" by
      balloon catheter: a combined radiologic and surgical approach.
AB  - Inflow control of a rapidly expanding or ruptured femoral anastomotic
      "pseudoaneurysm" can be fraught with hazard. Occlusion of an anastomotic femoral
      aneurysm with a balloon catheter offers the surgeon a simple method of gaining
      inflow control prior to surgery. After achieving inflow control with the balloon
      catheter, the surgeon can incise the anastomotic aneurysm without significant
      blood loss, control back bleeding with balloon occlusion catheters, and with
      relative ease and safety repair or replace the anastomotic aneurysm as indicated.
      An illustrative case is presented.

PMID- 7632560
TI  - Transaortic renal and visceral endarterectomy.

PMID- 7632561
TI  - Aortic dissection.

PMID- 7632563
TI  - HIV rate up as young gay men ignore safe sex advice.

PMID- 7632562
TI  - Enhanced patency of venous Dacron grafts by endothelial cell sodding.

PMID- 7632565
TI  - New system for special hospitals.

PMID- 7632564
TI  - More security needed.

PMID- 7632567
TI  - The making of memories?

PMID- 7632566
TI  - New age problems.

PMID- 7632569
TI  - The blurring of boundaries in the nursing role and function.

PMID- 7632568
TI  - Advising travellers on health abroad: Part 2.
AB  - In the second of two articles looking at health when travelling abroad, the
      author explores the hazards of leisure time, the management of illness abroad and
      looks at communicable diseases and how to prevent them. With malaria prophylaxis
      and reimbursement of travel vaccines currently under debate, the information in
      these articles should be of assistance to all nurses when giving advice to those
      travelling abroad.

PMID- 7632570
TI  - Stroke care and rehabilitation.

PMID- 7632573
TI  - It's a sell-out.

PMID- 7632572
TI  - Carers in conflict.

PMID- 7632571
TI  - Exploring men's health in a men-only group.
AB  - This article looks at one attempt to allow a particularly vulnerable group of
      men, those in contact with mental health services, to explore men's health issues
      in a men-only group environment. Based on an examination of current literature on
      men's health issues and feedback from participants in the group sessions, the
      authors suggest that nursing should rethink its position on the issue of men's
      health.

PMID- 7632574
TI  - Wish you were there.

PMID- 7632575
TI  - Beware people quoting figures.

PMID- 7632577
TI  - K is for knowledge.

PMID- 7632576
TI  - Labour--fudge or future?

PMID- 7632579
TI  - How safe are our children?

PMID- 7632578
TI  - Early shift in A&E.

PMID- 7632580
TI  - All right on the day?

PMID- 7632582
TI  - How to share the care.

PMID- 7632583
TI  - Hidden meanings.

PMID- 7632581
TI  - Getting a yellow card.

PMID- 7632584
TI  - Vote of confidence for breast care nurses.

PMID- 7632585
TI  - Sex education video to fill the gap.

PMID- 7632586
TI  - Tonsillitis on the tall ships.

PMID- 7632587
TI  - Palliative care. Spreading the word.

PMID- 7632588
TI  - The management and treatment of eczema.
AB  - This article outlines the principles of the treatment and management of eczema
      including the practical aspects of nursing patients with eczema. Awareness of
      basic dermatological nursing skills is important for all nurses as is an
      understanding of how to provide support and advice to patients and their
      families.

PMID- 7632589
TI  - Research issues in case management.
AB  - Case management and managed care are strategies for co-ordinating the services
      and care required by groups of patients in a variety of clinical areas. These
      systems have been described and discussed in a previous issue of Nursing Standard
      (1) which highlighted the fact that evidence used to support the effectiveness of
      these systems is currently very weak. The purpose of this article is to discuss
      some of the research and evaluation issues.

PMID- 7632590
TI  - The separatist movement within midwifery.

PMID- 7632591
TI  - Developing a new deal for nurses.
AB  - Boundaries between different healthcare professionals are rapidly being eroded by
      documents such as the New Deal and the Scope of Professional Practice. In this
      article, the author outlines the progress being made in one trust and calls for a
      'new deal' for nurses, whereby those who have proved themselves competent should
      have little or no limits to the boundaries of their practice.

PMID- 7632592
TI  - Orthopaedic nursing: a study of its specialty status.
AB  - This study attempts to clarify the distinction between orthopaedic and general
      nursing in response to criticism that orthopaedic nursing did not merit specialty
      status. The questionnaire survey asked nurses to assess a range of 76 nursing
      activities in terms of professional function. The results showed 36 out of the 76
      activities were identified as 'highly orthopaedic'. The author emphasises that
      the holistic nature of nursing also applies to orthopaedic nursing and that this
      requires both generic and specialist skills. The implication for nurse education
      is that the necessary skills may need to be taught to a higher level to match a
      specialty status.

PMID- 7632593
TI  - Out of chaos....

PMID- 7632594
TI  - Doubts and dilemmas.

PMID- 7632595
TI  - Quality at the bank.

PMID- 7632596
TI  - A better sort of training.

PMID- 7632597
TI  - Time to shape the agenda.

PMID- 7632599
TI  - Sex determination and DNA competition in the analysis of forensic mixed stains by
      PCR.
AB  - Sex determination of pure and mixed blood samples and stains was performed by
      amplification of the X-specific and Y-specific alphoid sequences by PCR (XY-PCR).
      From mixed blood samples with female DNA present in large excess of male DNA, the
      Y-specific sequence still amplified efficiently. In the analysis of vaginal
      secretions in a case of sexual assault, XY-PCR was performed to test the
      efficiency of the selective lysis procedure in order to investigate whether
      alleles found with other PCR systems were of male or female origin. Our studies
      with mixed blood samples revealed pronounced DNA competition in the HLA-DQ alpha
      and D1S80 PCR systems: the alleles from a minor DNA component could not be
      detected in the presence of a large excess of DNA from a second person.

PMID- 7632598
TI  - Odontological identification of fire victims--potentialities and limitations.
AB  - A retrospective study was performed to analyse the power of odontological
      evidence in burn victims. The material comprised 292 single fire cases registered
      at 4 centers of forensic odontology in Scandinavia (DK: Aarhus, Copenhagen; N:
      Oslo; S: Goteborg) covering a 10-year period. Filed antemortem (am) and
      postmortem (pm) data were critically reviewed and registered. New systems for
      classification of the degree of injuries to the teeth and jaws and of the quality
      of dental records were developed. Matching dental am-pm units/features were
      recorded using the tooth as unit. Units were scored as either ordinary or
      extraordinary if the frequency of occurrence in a Danish reference population was
      > or = 10% or < 10%, respectively. The ID conclusion of a single case was
      classified into one of the categories: no conclusion, ID possible, ID probable or
      ID established, depending on the number of ordinary/extraordinary matching units.
      All age groups were represented. Most fatal burns occurred in house fires (62%)
      and there was a preponderance of males (71%). Detailed written records supplied
      by single or by systematic radiographs were available in 71% of cases. About 50%
      of burn victims were classified into the no-injury group and approximately 25% of
      cases showed injuries to the anterior teeth only. The number and complexity of
      dental restorations increased with age. The dental examination was a powerful
      tool in identification of burn victims. Thus, dental identity (ID) was
      established in 61% of burn victims and dental evidence assisted the
      identification in another 31% (ID possible 19%; ID probable 12%).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7632600
TI  - Population study of 3 STR loci in the Basque Country (northern Spain).
AB  - The tetrameric STRs, HUMTH01, HUMVWA31A and HUMFES/FPS, were studied in a
      population from the Basque Country (northern Spain) for their frequency
      distribution and applicability to identity and paternity testing. All systems
      conformed to Hardy-Weinberg equilibrium; pairwise comparisons demonstrated the
      allelic independence between loci, and furthermore, all systems seemed to be in
      agreement with expectations from the Stepwise Mutation Model (SMM) of the
      mutation-drift theory, which indicates the homogeneity of the population and
      suggests a replication slippage mechanism as a possible model for generating
      alleles. A comparison with other population groups appeared to indicate that
      frequencies are well conserved in Caucasians, but differ from other racial
      groups. The calculated parameters "a priori probability of exclusion" (PEX) and
      "index of discrimination" (ID), show the informativeness of these loci for the
      determination of identity and relatedness of individuals.

PMID- 7632601
TI  - Swiss population data and forensic efficiency values on 3 tetrameric short tandem
      repeat loci-HUMTH01, TPOX, and CSF1PO-derived using a STR multiplex system.
AB  - Allele and genotype frequencies for 3 tetrameric short tandem repeat loci were
      determined in a Swiss population sample (n = 100) using the GenePrint STR
      Multiplex System, electrophoresis of the PCR products in DNA sequencing gels and
      subsequent detection of allelic fragments by silver staining. The loci are
      HUMTH01, TPOX, and CSF1PO. The observed heterozygosities are 83.0%, 60.0%, and
      72.0%, respectively. The discrimination power determined for the individual loci
      is 0.914, 0.780, and 0.860, respectively, and the combined discrimination power
      for the triplex is 0.997. All loci meet Hardy-Weinberg expectations and after
      Bonferroni correction there was no evidence that the population sample deviates
      from expectations of independence. Moreover, independence of alleles at these STR
      loci with other PCR-based loci derived from the same Swiss population sample,
      previously reported, were considered. These loci were DQA1, LDLR, GYPA, HBGG,
      D7S8, GC and D1S80. Again, after Bonferroni correction there was no evidence that
      the population sample deviates from expectations of independence among alleles at
      the 10 different PCR-based loci. Thus, the allelic frequency data can be used in
      human identity testing to estimate the frequency of a multiple PCR-based DNA
      profile in the Swiss population.

PMID- 7632602
TI  - "Terminal burrowing behaviour"--a phenomenon of lethal hypothermia.
AB  - Between 1978 and 1994, 69 cases of death due to lethal hypothermia were examined
      in our Institute. In addition to the common findings associated with hypothermia
      we especially wanted to examine the so-called paradox reaction which refers to
      the undressing of persons in a state of severe (lethal) hypothermia. This is
      obviously the result of a peripheral vasodilatation effecting a feeling of
      warmth. In our material this paradoxical undressing occurred in 25% of the cases
      and nearly all exhibited an additional phenomenon which has not yet been
      described in the literature. Nearly all bodies with partial or complete
      disrobement were found in a position which indicated a final mechanism of
      protection i.e. under a bed, behind a wardrobe, in a shelf etc.. This is
      obviously an autonomous process of the brain stem, which is triggered in the
      final state of hypothermia and produces a primitive and burrowing-like behaviour
      of protection, as seen in (hibernating) animals. This phenomenon, which we refer
      to as "terminal burrowing behaviour", occurred predominantly with slow decreases
      in temperature and moderately cold conditions.

PMID- 7632603
TI  - Temporal course of intravital and postmortem proliferation of epidermal cells
      after mechanical injury. An immunohistochemical study using bromodeoxyuridine in
      rats.
AB  - The temporal course of epidermal basal cell proliferation in the wound of the
      pinna of rats was studied using bromodeoxyuridine (BrdU) immunohistochemistry.
      Following incisional wounding, the animals were sacrificed at intervals ranging
      from 0 hours to 32 days. Two biopsies were taken from each animal, one
      intravitally and one postmortem after 24 hours storage at 8 degrees C. Specimens
      were incubated in a solution containing BrdU and embedded in paraffin. BrdU
      expression was demonstrated by a monoclonal antibody against BrdU. In both
      intravital and postmortem biopsies, the labelling indices increased significantly
      in the period from 32 to 60 hours post-injury. This suggests that DNS synthesis
      induced during life continues after death. Applied to forensic practice, the
      present findings point to the possibility of determining the vitality of a wound
      in postmortem tissue.

PMID- 7632604
TI  - Unsuspected (clinically silent) multiple sclerosis. Quantitative investigations
      in one autoptic case.
AB  - The incidental retrieval of a few, well-circumscribed, chronic multiple sclerosis
      plaques in a 49-year-old female who died from myocardial infarct is reported. In
      serial gallocyanin stained frontal sections of the brain one plaque in the left
      and four plaques in the right hemisphere were encountered. A total of 1.25 cm3 or
      0.24% of the right hemispheric volume and a total of 0.93 cm3 or 0.2% of the left
      hemispheric volume was afflicted. The size as well as the topography of the
      plaques could explain the absence of clinical symptoms. Methodological issues
      concerning in vivo and post mortem diagnosis of multiple sclerosis and their
      impact on the epidemiology of this disease are discussed.

PMID- 7632605
TI  - Fatal zipeprol intoxication.
AB  - A fatality resulting from ingestion of zipeprol is described. Capillary gas
      chromatography coupled to mass spectrometry was employed to quantify the drug in
      biological fluids and tissues. The femoral blood concentration of the drug was
      2.85 mg/L. Hair analysis clearly indicated chronic drug abuse with a
      concentration of 7.34 ng/mg. Results are discussed in the light of the existing
      literature.

PMID- 7632606
TI  - Characterization of dextromoramide (Palfium) abuse by hair analysis in a denied
      case.
AB  - By providing information on exposure to drugs over time, hair analysis is useful
      in verifying the history of drug use. In a clinical case, where drug abuse was
      denied, it was possible to identify dextromoramide in the hair of the subject.
      After acid hydrolysis of the hair with 0.1 M HCl, in the presence of SKF 525A as
      an internal standard, the drug was extracted at pH 8.4 with chloroform
      isopropanol-n-heptane (50:17:33 v/v) and quantified by gas chromatography/mass
      spectrometry. The hair strands were cut into 3 sections of 2.5 cm, corresponding
      to a growth period of 2 months. Concentrations were 1.09, 1.93 and 1.48 ng/mg
      from the root to the end, respectively. This is the first report on
      dextromoramide testing in human hair.

PMID- 7632607
TI  - AMPFLP analysis of the VNTR loci D1S80 and ApoB in Hungary.
AB  - Population data studies for D1S80 and ApoB were carried out on a caucasian
      population sample from Hungary of 229 and 222 unrelated individuals,
      respectively. We observed 26 different alleles for D1S80 and 13 for ApoB. The
      allele frequencies found are similar to those reported in the literature for
      European caucasians. No evidence of significant deviations from Hardy-Weinberg
      equilibrium were observed for both AMPFLP systems.

PMID- 7632608
TI  - Molecular mechanism of androgen-dependent growth in transformed cells. Pathway
      from basic science to clinical application.
AB  - Shionogi carcinoma 115 (SC 115) has been extensively used to analyze the
      mechanism of androgen-dependent cancer growth. This tumor exhibits marked
      androgen-dependent growth in vivo and one cell line whose growth is markedly
      stimulated by androgen in serum-free culture condition is isolated from SC 115
      tumor. This androgen-dependent growth is mediated through an induction of heparin
      binding growth factor termed as androgen-induced growth factor (AIGF). In
      addition, fibroblast growth factor receptor 1 (FGFR 1) is identified as a
      receptor for AIGF. The expression of FGFR 1 mRNA is up-regulated by androgen in
      SC 115 cells, indicating that this androgen-inducible autocrine loop is
      potentiated at two sites by androgen. An androgen-independent cell line is also
      established from this androgen-dependent SC 115 tumor. The growth of these
      androgen-independent cells is stimulated by AIGF, indicating that AIGF acts not
      only as an autocrine growth factor to androgen-dependent cells but also as a
      paracrine growth factor to androgen-independent cells. In addition, transfection
      of AIGF expression vector into androgen-dependent cells results in a facilitation
      of conversion from androgen-dependent to -independent phenotype. Thus, AIGF might
      play a role from tumor progression. These results indicate that a blockade of
      AIGF activity is an important therapeutic target. Actually, some compounds such
      as heparin and suramin are found to inhibit this androgen-induced autocrine loop.
      These basic observations will be discussed in relation to their possible clinical
      application.

PMID- 7632609
TI  - Crystallization and X-ray investigation of vitamin D-binding protein from human
      serum. Identification of the crystal content.
AB  - Vitamin D-binding protein (DBP), a multifunctional, highly polymorphic
      glycoprotein responsible for the transport of vitamin D and for sequestering
      extracellular actin, was isolated from human serum and crystallized using vapour
      diffusion methods. The crystals were grown from 7.5% v/v polyethylene glycol 400
      and 0.1 M acetate buffer at pH 4.6. These crystals show diffraction patterns
      consistent with the tetragonal space groups P4(1) and P4(3) with unit cell
      dimensions a = b = 135.5(4) A and c = 75.9(4) A. They diffract to 2.3 A. Using
      polyacrylamide gel electrophoresis it was shown that according to their
      electrophoretic mobility the O-glycosylated isoforms, with a terminal sialic acid
      residue, are absent in the crystals.

PMID- 7632610
TI  - Estrogen increases the density of 5-hydroxytryptamine(2A) receptors in cerebral
      cortex and nucleus accumbens in the female rat.
AB  - Estrogen exerts a profound effect on mood and mental function in man. Based on
      our finding that estradiol selectively stimulates the expression of 5
      hydroxytryptamine(2A) (5-HT2A) receptor mRNA in the dorsal raphe nucleus of the
      female rat, we investigated the effects of estradiol on the density of 5-HT2A
      receptors in brain. The distribution and density of 5-HT2A receptors were
      determined by in vitro binding of [3H]ketanserin in the presence of prazosin to
      exclude binding to alpha 1-adrenoreceptors. Brains were collected, processed and
      analysed in pairs from six estradiol- and six vehicle-treated animals. Our
      results show that a single pulse of estradiol induces a significant increase in
      the density of 5-HT2A receptors in female rat forebrain, particularly the
      anterior frontal, anterior cingulate and primary olfactory cortex and the nucleus
      accumbens. Since these brain regions play a pivotal role in cognition and
      emotion, as well as neuroendocrine and motor control, our findings provide the
      first experimental evidence for the fact that estrogen could alter mood and
      mental state by increasing the density of 5-HT2A receptors in cerebral cortex and
      nucleus accumbens.

PMID- 7632611
TI  - Progression to steroid autonomy is accompanied by altered sensitivity to growth
      factors in S115 mouse mammary tumour cells.
AB  - Progression to steroid autonomy is a major clinical problem in the treatment of
      steroid-sensitive tumours. Molecular mechanisms remain unknown but recent
      hypotheses imply a role for growth factors in this progression. Since S115 + A
      androgen-responsive mouse mammary tumour cells provide a model system to study
      this phenomenon in vitro, we have used this model to investigate growth factor
      gene expression and sensitivity during progression from a steroid sensitive to
      insensitive state. S115 + A androgen-responsive cells showed a positive
      proliferative response, morphological response and increased saturation density
      to various forms of fibroblast growth factor (FGF) and transforming growth factor
      beta (TGF beta) in both monolayer and suspension culture. A marked synergy was
      noted, however, between FGF and TGF beta in promoting growth in suspension
      culture. S115 + A cells possessed mRNA for both acidic FGF (aFGF) and TGF beta 1,
      both of which were increased by testosterone. Progression to androgen
      insensitivity was associated with a reversal of growth factor response such that
      all growth factor responses became generally inhibitory on growth of the
      unresponsive cells but with a particularly striking synergistic action between
      FGF and TGF beta 1 on inhibition of both monolayer and suspension growth. Levels
      of aFGF and TGF beta 1 mRNAs remained low in steroid-insensitive S115-A cells,
      indicating that loss of response was not associated with any constitutive
      upregulation of endogenous production of one of these growth factors. The
      scientific and clinical implications are discussed.

PMID- 7632612
TI  - Regulation of guinea pig adrenal P450c21 messenger RNA, protein and activity by
      RU486.
AB  - The role of ACTH, forskolin and 8Br-cAMP on the regulation of mRNA abundance,
      protein levels and enzymatic activity of cytochrome P450 21-hydroxylase (P450c21,
      CYP21) were investigated in guinea pig adrenal cell cultures. In untreated cells,
      21-hydroxylase activity was diminished throughout a 48 h period of incubation.
      Although incubation with forskolin and 8Br-cAMP restored 21-hydroxylase activity
      to normal levels, the addition of ACTH did not prevent the decrease of 21
      hydroxylase activity. Treatment of cells with RU486 for 24 h inhibited 21
      hydroxylase activity by 93%; however, after removal of the drug a slight increase
      of enzyme activity was observed; this rise was enhanced by the addition of ACTH.
      Forskolin and 8Br-cAMP increased the levels of 21-hydroxylase activity to the
      same range as seen in untreated cells. In cells that were not pretreated with
      RU486, incubation with cycloheximide for 1 h had no effect on 21-hydroxylase
      activity and could not prevent the modest increase of 21-hydroxylase activity
      induced by forskolin or 8Br-cAMP after 48 h of incubation. In RU486-treated
      cells, cycloheximide blocks the stimulation of enzyme activity induced by ACTH,
      forskolin and 8Br-cAMP. Our findings indicate that 21-hydroxylase activity can be
      stimulated by ACTH, forskolin or 8Br-cAMP solely in the presence of reduced
      enzymatic activity. Western immunoblot analysis of P450c21 protein levels in
      untreated or RU486-treated adrenal cells indicate that P450c21 protein levels
      were in the same range and further incubation with ACTH caused a similar
      elevation of P450c21 protein levels in both the untreated and RU486-treated
      cells. Northern blot analysis on RNA isolated from adrenal cells showed that
      RU486 did not alter the basal steady state levels of P450c21 mRNA. As well,
      incubation with ACTH or 8Br-cAMP increased the levels of P450c21 transcript to
      the same extent in both untreated and RU486-treated cells. These results taken
      together provide additional evidence for the presence of an adrenal specific
      protein factor(s) modulating 21-hydroxylase activity.

PMID- 7632613
TI  - A one minute pulse of estradiol to MCF-7 breast cancer cells changes estrogen
      receptor binding properties and commits cells to induce estrogenic responses.
AB  - Changes in estradiol (E2)-binding parameters can be detected within minutes,
      while the estrogenic responses are manifested after several hours or days of
      continuous exposure to the steroid. The goal of this study was to determine the
      time of commitment for the induction of transcription-dependent responses in the
      human breast cancer cell line MCF-7. In cultures grown in steroid-deprived serum,
      a pulse of 1 nM E2 as short as 1 min was sufficient to maximally increase the
      level of the progesterone receptor, as determined by binding of the progestin
      [3H]ORG.2058 after 2 days, and to partially stimulate cell proliferation for 5
      days. From uptake experiments it was calculated that after 1 min about 7000 E2
      molecules were bound per cell, enough to occupy 5% of the approx. 150,000
      estrogen receptors per cell. Preincubating cells with unlabelled E2 for 1 min
      lead to a loss of [3H]E2-binding capacity. As analysed by Scatchard plot, this
      loss was due to a decrease in the number of exchangeable binding sites and, to a
      lesser extent, to an increase in the dissociation constant. For up to 30 min of
      E2-incubation the level of receptor protein remained constant as determined by
      immunoassay with the anti-ER monoclonal antibodies D547 and H222. The
      dissociation kinetics of [3H]E2 bound by MCF-7 cells after a 5 min pulse were
      biphasic, with the slower phase having a rate of 2.3 x 10(-3) min. This rate is
      characteristic of the activated ER. The estrogenic response is thus committed by
      E2 within less than 1 min and evoked by the activation of a small fraction of
      estrogen receptors.

PMID- 7632614
TI  - Chemoprevention by dietary dehydroepiandrosterone against promotion/progression
      phase of radiation-induced mammary tumorigenesis in rats.
AB  - When pregnant rats received whole body irradiations with 260 cGy gamma-ray at day
      20 of pregnancy, and were then implanted with a diethylstilbestrol (DES) pellet
      for an experimental period of 1 year under feeding of a control diet, a high
      incidence (96.2%) of mammary tumors was observed. Administration of dietary 0.6%
      dehydroepiandrosterone (DHEA) together with DES implantation significantly
      decreased the incidence (35.0%) of mammary tumors. The first appearance of
      palpable tumors in the DHEA-fed group was 4.5 months later than that in the
      control group. For clarification of the mechanism of the chemopreventive action,
      we measured hormone levels in the serum of DHEA-fed rats. In the DHEA diet rats,
      the concentration of estradiol-17 beta exceeded, by approximately 6-fold, that in
      the control rats, while the levels of progesterone and prolactin were decreased
      by 30 and 45%, respectively. Interestingly, DHEA feeding prevented DES-induced
      hypertrophy of pituitary glands and DES-induced high level of prolactin in
      pituitary glands detected by immunohistochemical studies, but stimulated the
      development of mammary glands more than that in control rats treated with DES
      alone. These findings suggest that DHEA has a potent preventive activity against
      the promotion/progression phase of radiation-induced mammary tumorigenesis. The
      mechanism of chemoprevention by change of endocrinological environment is
      discussed.

PMID- 7632615
TI  - A role for protein tyrosine kinase in the steroidogenic pathway of angiotensin II
      in bovine zona glomerulosa cells.
AB  - Stimulation of aldosterone synthesis in bovine adrenal zona glomerulosa (ZGB)
      cells by angiotensin II (AngII) is believed to be mediated by the phospholipase C
      (PLC) pathway that results in the increase of cytosolic free calcium
      concentration and in the activation of protein kinase C (PKC). However, the cell
      proliferation and contraction associated with AngII action are known to be
      mediated in part by protein tyrosine kinases (PTK). To assess the potential role
      of PTK in the stimulatory effect of AngII on adrenal steroidogenesis, the actions
      of a series of PTK inhibitors on this metabolic pathway were examined in isolated
      ZGB cells. Tyrphostin 23 (TP23) caused a dose-dependent inhibition of AngII
      stimulated aldosterone production with an IC50 of 15 microM and reached complete
      inhibition at 100 microM. Genistein (GS) was more potent with an IC50 of 35 nM
      and complete inhibition at 10 microM. The stimulation of aldosterone production
      by the calcium-mobilizing agent thapsigargin (Thaps) was also dose-dependently
      inhibited by TP and GS with the same potency. A specific PKC inhibitor,
      calphostin C (0.1 microM) caused only a 51.7% inhibition of AngII-stimulated
      aldosterone production. In the same way, a specific Ca2+/calmodulin-dependent
      protein kinase inhibitor, KN-62 (1 microM), reduced aldosterone production
      stimulated by AngII by 64%. As expected, thapsigargin-stimulated aldosterone
      biosynthesis was not affected by calphostin C, but was completely inhibited by KN
      62. These results demonstrate for the first time that protein tyrosine kinase
      activity is part of the angiotensin II signalling pathway in bovine zona
      glomerulosa cells. The activation of this PTK occurs subsequently to the
      mobilization of intracellular calcium. This calcium-dependent protein tyrosine
      kinase pathway is essential for the steroidogenic response to AngII in bovine
      zona glomerulosa cells.

PMID- 7632616
TI  - Specific interactions of progestins and anti-progestins with progesterone
      antibodies, plasma binding proteins and the human recombinant receptor.
AB  - This structure-activity study compares the affinity of a series of progestins,
      progesterone metabolites and anti-progestins for a panel of monoclonal antibodies
      to progesterone, coypu (Myocastor coypus) or guinea pig plasma progesterone
      binding proteins (PPBPs) and the human recombinant progesterone receptor A form
      (PR-A). The compounds tested were progesterone, Promegestone (R5020),
      Mifepristone (RU486), ZK98,734, Onapristone (ZK98,299), 11 alpha
      hydroxyprogesterone, 11 alpha-progesterone hemisuccinate, androsterone,
      etiocholanolone, 5 alpha- and 5 beta-pregnane-3,20-diones, and 20 alpha- and 20
      beta-hydroxyprogesterones. The Ki values for these ligands were determined by
      competitive binding assays using radiolabelled progesterone as the binding site
      ligand. For anti-progesterone antibodies (e.g. DB3 and 11/32), only progesterone
      (3.6-8.8 nM), the 11 alpha-derivatives (1.0-5.5 nM) used to prepare the immunogen
      and the two 5-pregnanediones (20.9-45.1 nM) were bound with high affinity. For PR
      A, high affinity binding was found with receptor agonists (Ki = 1.1-6.2 nM), both
      5- and 20-reduced metabolites, and antagonists (0.6-28.0 nM), but not with the 11
      alpha-derivatives (950 nM-1.0 microM). In contrast, the PPBPs displayed high
      affinity interactions with progesterone (3.5-4.2 nM) and both 5 alpha- and 20
      alpha-reduced metabolites (2.4-3.4 nM). Binding with the beta-isomers and R5020
      was less pronounced (22-170 nM) and there was no evidence of high affinity
      binding with PR antagonists (> 1.0 microM). Analogs with the 17-keto group did
      not bind to any of the binders studied. Thus, commonalities among the three types
      of protein binders were their comparable binding affinities for progesterone (3.5
      8.8 nM) and 5-pregnanedione isomers (2.4-330 nM), and a lack of binding for two
      C17-keto steroids (androsterone and etiocholanolone). The results imply that the
      tertiary features of the binding domain of these three types of proteins are
      sufficiently different to result in unique binding structures.

PMID- 7632617
TI  - Oestrogenic activity of an environmentally persistent alkylphenol in the
      reproductive tract but not the brain of rodents.
AB  - Compounds with oestrogenic actions present in the environment as a result of
      human activity may represent a threat to health and reproductive efficiency in
      human and wildlife populations. We show here that parenteral administration of
      octylphenol, a recently described environmental oestrogen derived from one group
      of non-ionic surfactants, is active in stimulating oestrogen-dependent uterine
      growth in prepubertal rats, but has no influence on perinatal sexual
      differentiation of the rat brain. These results extend previous in vitro findings
      to show that alkylphenols exert weak oestrogenic activity in vivo in mammals.

PMID- 7632618
TI  - The cecum does not participate in the stimulation of intestinal calcium
      absorption by calcitriol.
AB  - Intestinal Ca absorption from the diet consumed during one night was measured in
      male rats fed a normal (0.5%) Ca, low fiber (3% cellulose) diet by determining
      the decrease in 47Ca/47Sc ratio between diet and feces. One-half of the rats had
      been cecectomized 9 weeks previously at 14 weeks of age. Calcitriol injections,
      given intraperitoneally the morning of the experiment, stimulated fractional
      intestinal Ca absorption 2.5-fold in intact rats (16.9 +/- 2.0% to 42.2 +/- 1.8%)
      and 2.3-fold in cecectomized rats (20.1 +/- 1.4% to 46.8 +/- 1.2%). Similar
      results were obtained when the data were calculated in terms of total Ca
      absorption expressed as mg/day. Thus, although the cecum can absorb Ca when diets
      contain large amounts of digestible fiber, cecectomy does not influence the
      stimulation of intestinal Ca absorption induced by calcitriol in vitamin D
      replete rats fed a low fiber diet.

PMID- 7632619
TI  - Effects of dexamethasone on steroidogenesis in Leydig cells from rats of
      different ages.
AB  - The effects of 0.1 microM dexamethasone on cytochrome P450 content, 3 beta
      hydroxysteroid dehydrogenase (3 beta-HSD) activity, and basal and LH-induced
      testosterone production of Leydig cells from rats 3, 5, 7 and 10 weeks old were
      examined. The cytochrome P450 content of Leydig cells from rats 3 weeks old was
      increased by treatment with dexamethasone for 22 h, while 3 beta-HSD activity was
      decreased. The cytochrome P450 content of Leydig cells from rats 5 weeks old was
      increased after 3 and 22 h of culture, while 3 beta-HSD activity was decreased
      after 22 and 44 h of treatment. The cytochrome P450 content of rats 7 weeks old
      was increased after 3 h of culture, while 3 beta-HSD activity was decreased after
      22 and 44 h of culture. Leydig cells from rats 10 weeks old showed increased
      cytochrome P450 content upon dexamethasone treatment after 3 h. The activity of 3
      beta-HSD was decreased after 44 h of treatment. In Leydig cells from rats 3 and 5
      weeks old, dexamethasone decreased basal testosterone production after 22 h of
      treatment, but not after 44 h, and did not affect LH-induced testosterone
      production. Leydig cells from rats 7 weeks old showed decreased basal and LH
      induced testosterone production, when treated with dexamethasone for 22 and 44 h.
      Basal testosterone production was unaffected by dexamethasone in rats 10 weeks
      old, while LH-induced testosterone production was decreased after 44 h of
      treatment. The effect of dexamethasone on testosterone secretion changed during
      development, as a transient, early effect on basal testosterone secretion was
      observed in Leydig cells from prepubertal and pubertal rats. These data suggest
      that dexamethasone affects Leydig cells differently, depending on the age of the
      rat, the older rats being more sensitive than the younger rats.

PMID- 7632620
TI  - Chemometric evaluation of urinary steroid profiles in doping control.
AB  - Ten endogenous steroid hormones and metabolites were determined according to the
      screening procedure for anabolic steroids in spot urine samples from 105 healthy
      young male athletes (control samples) and 23 males that tested positive for
      anabolic steroids in the doping control (positive samples). The GC-MS peak areas
      for each sample were normalized to total area. Multivariate data analysis by
      Partial Least Square Regression (PLSR) and using a coded Y-variable (positive
      samples: +1 and control samples -1) allows projection of the most systematic
      profile structures into a 2D plot revealing a clear distinction between the
      control and misuser groups. The most important determinants of the location in
      the loading plot were the ratios of testosterone to epitestosterone and
      androsterone to etiocholanolone. The ratio between 11-beta-hydroxyandrosterone
      and 11-beta-hydroxy-etiocholanolone was less important, in accordance with the
      fact that anabolic-androgenic steroid intake primarily affects the excretion of
      testosterone from the testis and to a much lesser degree adrenal steroid genesis.
      We present a preliminary validation of this model (PLS1-DISCRIM) for analysing
      steroid profiles in doping control samples from several categories of athletes,
      some of which are suspected for drug misuse, and results from a one dose
      excretion study in healthy volunteers. Our findings suggest that use of
      multivariate PLS-regression may give valuable information about anabolic
      androgenic steroid misuse in sport. When appropriately calibrated, this
      methodology may delineate drug misusers directly from the screening procedure for
      anabolic steroids in spot urine tests.

PMID- 7632621
TI  - Language and thought disorder in schizophrenia: brain morphological correlates.
AB  - In this magnetic resonance imaging study, the authors analyzed the relationships
      between frontal and temporal lobe volumes, volumes of ventricular system
      subdivisions and clinical and neuropsychological aspects of language and thought
      disorder in a group of 19 young schizophrenic patients. Schizophrenics showed
      enlargement of lateral ventricles, especially of the central and occipital
      segments compared with 15 age and sex matched healthy controls but no differences
      were present in prefrontal, temporal lobe and superior temporal gyrus volumes.
      Prefrontal volume was inversely correlated with Thought, Language and
      Communication (TLC) scale total scores; left superior temporal gyral (STG) volume
      was positively correlated with verbal fluency test performance; higher total
      ventricular volume was significantly correlated with poor performance to a
      sentence generation test; STG laterality index was correlated with global TLC
      scores, the more severe the thought and language disorders, the relatively
      smaller the left and larger the right STG. These results suggest a complex
      neuroanatomical substrate for thought and language disorders in schizophrenia.

PMID- 7632622
TI  - Differences in qualitative brain morphology findings in schizophrenia, major
      depression, bipolar disorder, and normal volunteers.
AB  - This study examined the frequency and type of qualitative brain morphologic
      anomaly as a function of sex and diagnosis. Magnetic resonance imaging brain
      scans were evaluated by an experienced neuroradiologist blind to diagnosis. The
      scans of 325 individuals (108 schizophrenic, 20 schizoaffective, 27 major
      depressive, 20 bipolar and 150 healthy volunteers) were categorized into one of
      five groups: normal, hyperintensity signals, volume loss, ventricular anomaly or
      "other" abnormality. Schizophrenic men had significantly more morphologic
      anomalies, especially of the lateral ventricles than healthy male volunteers.
      Schizophrenic women did not differ from healthy women. Schizoaffective patients
      of both sexes, male depressive and female bipolar patients were also
      characterized by higher rates of brain anomalies. Independent of diagnosis, women
      were more likely than men to have hyperintensity signals among individuals with
      positive scan findings. The overall rate of brain morphologic anomalies is
      significantly higher among male schizophrenic patients than healthy volunteers;
      this is not specific to male schizophrenics, however, suggesting a global sex
      effect. Type of anomaly may differ by sex and give us clues about sex differences
      in the pathophysiology of psychopathology.

PMID- 7632624
TI  - Methodological aspects of onset assessment in schizophrenia.
AB  - Psychiatric disorders in general and schizophrenia in particular often begin with
      a prodromal phase progressing into more specific syndromes long before the first
      treatment contact. More longitudinal studies on course and outcome of
      schizophrenia begin with first hospital admission not taking into account the
      preceding early course. The reason for this is the unsurmountable difficulties in
      observing and assessing real onsets with unspecific symptomatology directly and
      collecting a sufficient number of 'precontact' cases of rare diseases in the
      general population. There are in principle two practical ways of assessing time
      and type of onset and the early course of schizophrenia: the application of a
      screening procedure for establishing a prospective approach, e.g. the study of
      individuals at high risk for schizophrenia, and the retrospective assessment of
      the preceding course carried out at first treatment contact. Methodologically
      both strategies share the same problems, especially recall bias. In a
      comprehensive discussion of methodological issues ways are described to reduce
      and even control recall deficits by using appropriate techniques (standardised
      assessment with the IRAOS, the 'Interview for the Retrospective Assessment of the
      Onset of Schizophrenia'; time grids; interval assessment, comparison of
      independent sources of information etc.). A representative sample of 232 patients
      with a first episode of schizophrenia were selected from the 276 first admissions
      of the ABC schizophrenia study taken from a German population of 1.5 million.
      Results are represented for the crucial questions: when, how and with what
      symptoms does schizophrenia begin and how does the disorder develop up to the
      first admission? For example, the gender-specific mean age at different points in
      time during the development of the disease is presented, and the sequence and
      cumulation of symptoms in the early course examined. Additionally, the
      consecutive fulfillment of DSM-III criteria sets for schizophrenic and
      schizophreniform disorders are presented along with the frequency of different
      types of onset in schizophrenia.

PMID- 7632623
TI  - Are there patients with late-onset schizophrenia in state hospitals?
AB  - Diagnoses of all individuals admitted between 1989 and 1991 to a State of
      Illinois Hospital were examined to determine the prevalence of patients meeting
      DSM-III-R criteria for late-onset schizophrenia. Four prevalence rates were
      determined for each year based on the frequency of late-onset patients in (1)
      total psychiatric admissions, (2) total admissions over age 45, (3) admissions
      with diagnoses of schizophrenia, and (4) admissions over age 45 and diagnosed
      schizophrenia. Results showed that the mean (across the three years) of the four
      prevalence rates of late-onset schizophrenia ranged from 0.24% to 4.1%. This
      range is far below prevalence rates on hospitalized patients previously reported
      in the literature (6 to 34%). Reasons for discrepancy are discussed.

PMID- 7632625
TI  - Morbid risk of schizophrenia for relatives of patients with cannabis-associated
      psychosis.
AB  - Twenty-three patients admitted with acute psychosis who were cannabis positive on
      urinary screening were each matched, with respect to sex, with two psychotic
      controls who screened negatively for all substances. The lifetime morbid risk of
      psychiatric disorder was estimated among the first degree relatives of cases and
      controls, using RDC-FH criteria to define diagnoses, and Weinberg's shorter
      method of age correction. The cases had a significantly greater familial morbid
      risk of schizophrenia (7.1%) than the controls (0.7%), while the risks of other
      psychoses, and of non-psychotic conditions were similar. The same pattern of
      familial risk was evident when the analysis was restricted to patients with DSM
      III schizophrenia. The data suggest that the development or recurrence of acute
      psychosis in the context of cannabis use may be associated with a genetic
      predisposition to schizophrenia.

PMID- 7632626
TI  - Comparison of indices of premorbid function in schizophrenia.
AB  - There has been a resurgence of interest in the area of premorbid functioning in
      schizophrenia as it provides clues to onset and etiology. Most studies rely on
      retrospective estimates of premorbid status that are incomplete, such as the
      Premorbid Adjustment Scale (PAS). Even prospective high-risk studies are hampered
      by the narrow range of premorbid functions assessed and are thus unable to answer
      crucial questions related to onset of illness. This study was undertaken to
      assess the relationship between several indices of premorbid functioning. Sixty
      four in-patients with schizophrenia were assessed at medication-free baseline and
      post-treatment with BPRS and SANS. PAS scores were derived from all available
      sources. Premorbid cognitive ability was estimated by the mean of WAIS-R
      Vocabulary and Information subscale scores. Estimated premorbid IQ was obtained
      using a demographic regression formula. Years of education and predicted VIQ,
      PIQ, and FSIQ were found to correlate with estimated premorbid cognitive ability.
      Predicted VIQ, PIQ, and FSIQ were associated with years of education and PAS
      childhood, early and late adolescence, and general scores. Each estimate of
      premorbid ability demonstrated a different pattern of association with clinical
      ratings, symptom change, and outcome. The results suggest that education, PAS,
      predicted IQ, and WAIS-R estimates of premorbid cognitive ability assess
      different but overlapping areas of pre-morbid functioning.

PMID- 7632627
TI  - Affect processing in chronically psychotic patients: development of a reliable
      assessment tool.
AB  - We developed an economical clinical tool for assessing affect processing deficits
      in patients with chronic schizophrenia and schizoaffective disorder. Using
      trained raters, we assessed spontaneous prosody, prosodic comprehension, prosodic
      repetition, and recognition of facial affect. High interrater reliability and
      good separation between subscales was demonstrated. Our tool discriminated
      between the performance of subjects versus controls on measures of spontaneous
      prosody and prosodic comprehension, suggesting the presence of prosodic deficits
      in psychiatric patients. These findings underscore the need for reliable and
      valid testing tools which will allow greater understanding of affective prosodic
      processing deficits in psychiatric populations.

PMID- 7632628
TI  - Associative learning in acutely ill and recovered schizophrenic patients.
AB  - Eight acutely ill deluded schizophrenic patients were compared with eight matched
      recovered patients on an associative learning task. Ten word pair associations
      were presented over five trials. Subsequently the subjects were presented with
      ten novel pairings over three trials, one word from the first pair associated
      with a new partner. Recovered patients performed better than acutely ill patients
      on both stages of the task. This result does not support the neuropsychological
      model of Gray et al. (1991) which predicts that acute schizophrenia is
      characterised by a weakening of the effect of previous experience on new
      learning.

PMID- 7632629
TI  - A quantitative sleep-EEG study on the effects of benzodiazepine and zopiclone in
      schizophrenic patients.
AB  - Polysomnographic examinations (PSG) were performed on 6 male schizophrenic
      outpatients who were being treated with benzodiazepine (BZD) hypnotics in
      combination with neuroleptics and 6 healthy male volunteers. In schizophrenic
      subjects, zopiclone (ZPC), 15 mg/day, was substituted for the BZD hypnotics, and
      PSGs were recorded again during ZPC therapy. All-night sleep stage scoring was
      carried out by visual analysis, and computerized period-amplitude analysis of
      sleep EEG was also performed. The schizophrenics showed marked reduction in the
      amount of slow-wave sleep (SWS) and in the number of delta half-waves during all
      night sleep, especially those with higher amplitude, as compared to the normals.
      The number of delta half-waves in the patients was markedly reduced during the
      first sleep cycle. The average amplitude of delta half-waves during all-night
      sleep in the schizophrenics was significantly lower than that in the normals. The
      half-wave count of total delta waves in the schizophrenics was higher during
      treatment with ZPC than with BZDs, although no significant differences were
      observed in the amount of SWS between the two treatments. Soundness of sleep in
      the subjective sleep assessment was better evaluated during treatment with ZPC
      than BZDs. These results suggest that reduction of SWS in schizophrenia may be
      attributable mainly to the decrease in the number of delta waves with higher
      amplitude and that ZPC may induce deeper sleep in schizophrenics than BZDs.

PMID- 7632630
TI  - Is third trimester abortion justified?

PMID- 7632631
TI  - After Cairo.

PMID- 7632632
TI  - Reducing the risk of blood borne infection in surgical practice.

PMID- 7632633
TI  - Historical representations of the pelvis.

PMID- 7632634
TI  - Down's syndrome births and pregnancy terminations in 1989 to 1993: preliminary
      findings.
AB  - OBJECTIVE: To investigate changes in the numbers of Down's syndrome births and
      terminations of pregnancies from 1989 to 1993. DESIGN: Data from a national
      register of cytogenetic diagnoses of karyotypes associated with Down's syndrome
      were analysed to obtain observed numbers of births and terminations of
      pregnancies known to be affected. Allowance was made for those cases diagnosed
      prenatally for whom the eventual outcome of the pregnancies had not yet been
      ascertained. RESULTS: There has been an increase over the study years in the
      number of cytogenetic diagnoses of Down's syndrome from 1063 in 1989 to 1137 in
      1993, despite an overall fall in births in England and Wales. This is largely due
      to the increase in antenatal screening and diagnosis, but in part also due to the
      rise in numbers of pregnancies at increased maternal ages. The rise in prenatally
      diagnosed cases, of which 92% end in termination, has been accompanied by a fall
      in both the estimated numbers of affected live births, from 764 in 1989 to 615 in
      1993, and the rate per 1000 total live births in the same years from 1.1 to 0.9.
      CONCLUSIONS: Better and speedier information on the outcome of prenatally
      diagnosed cases of congenital anomalies such as Down's syndrome would improve the
      quality of information available for those auditing genetic services or those
      planning for the care of survivors.

PMID- 7632635
TI  - The effect of maternal pushing on fetal cerebral oxygenation and blood volume
      during the second stage of labour.
AB  - OBJECTIVE: To measure the effect of maternal pushing during the second stage of
      labour on fetal cerebral oxygenation and blood volume. DESIGN: A prospective
      study comparing changes in the fetal cerebral concentrations of oxyhaemoglobin,
      deoxyhaemoglobin and cerebral blood volume, before and during maternal pushing in
      the second stage of labour. SETTING: Teaching hospital obstetric unit. SUBJECTS:
      Ten term fetuses during labour. RESULTS: Following the onset of maternal pushing,
      mean cerebral deoxyhaemoglobin concentration increased by a mean of 0.79 (SD
      0.59) mumol.100 g-1, (P < 0.01) without any consistent change in the
      oxyhaemoglobin concentration. These changes were associated with a significant
      decrease in the calculated mean cerebral oxygen saturation from a mean of 46.8%
      (SD 8.6) to 38.1% (SD 5.2) (P < 0.01). Pushing was also associated with a
      significant increase in the mean cerebral blood volume, which rose by a mean of
      0.33 ml.100 g-1 (SD 0.37) (P < 0.05). CONCLUSION: Maternal pushing during the
      second stage of labour leads to a significant decrease in fetal cerebral
      oxygenation, together with an increase in cerebral blood volume.

PMID- 7632636
TI  - The prediction of fetal acidosis at birth by computerised analysis of intrapartum
      cardiotocography.
AB  - OBJECTIVE: To assess the capability of a computer software interpretation
      program, using intrapartum fetal heart rate and intrauterine pressure as recorded
      in a cardiotocogram to predict fetal acidosis at birth. DESIGN AND SUBJECTS: A
      retrospective analysis of digitised fetal heart rate and uterine activity values
      obtained from 73 high risk women in labour. SETTING: Two university teaching
      hospitals. METHODS: A computer software program was constructed to analyse the
      digitised data and predict acidosis. The results of the analysis were compared
      with actual umbilical arterial blood pH and base excess at delivery. RESULTS: The
      software cardiotocogram interpreter was able to predict a pH of less than 7.15
      with an accuracy of 77%, a sensitivity of 88% and specificity of 75% in this set
      of data. It was able to predict a base excess of less than -8 mmol/l with an
      accuracy of 81%, a sensitivity of 76% and specificity of 82%. CONCLUSIONS: A
      computerised method of analysing fetal heart rate and uterine activity using a
      simple algorithm has demonstrated a capability to predict fetal acidosis at the
      time of delivery. Further research in this area is warranted.

PMID- 7632637
TI  - Evaluation of flexible senior registrar training in obstetrics and gynaecology.
AB  - OBJECTIVE: To evaluate part-time senior registrar training in obstetrics and
      gynaecology from the perspective of the trainees. DESIGN: Postal questionnaire.
      SUBJECTS: Past and present senior registrar trainees on the PM(79)3 scheme.
      RESULTS: Thirty-two questionnaires were returned (86% response rate) from 20
      current trainees (100% response) and 12 (71% response) past trainees. Family
      commitments were the main reason for training part-time. Of these, 84% were
      satisfied with their training and most (81%) thought the quality as good or
      better than full time training. Personalised timetables were seen to be of
      particular benefit. Negative attitudes towards part-time training and
      discrimination in favour of full time trainees were seen as some of the biggest
      difficulties associated with part-time training. Other problems included
      administrative delays in organising part-time posts, time restriction, and the
      length of training. CONCLUSIONS: Part-time senior registrar training is effective
      in retaining trainees with domestic commitments within the speciality. It is
      regarded as being of high quality but with attendant problems, particularly those
      related to the negative attitudes of others. Recommendations for improvements
      have been made.

PMID- 7632638
TI  - Fertility and pregnancy outcome following large loop excision of the cervical
      transformation zone.
AB  - OBJECTIVE: To determine if large loop excision of the transformation zone affects
      subsequent fertility and pregnancy outcome. DESIGN: A case-control study.
      SETTING: A teaching hospital serving a regional population. SUBJECTS: One
      thousand women who had undergone large loop excision of the transformation zone
      (LLETZ) for the treatment of cervical intraepithelial neoplasia (CIN) between
      1989 and 1991. Two controls were matched for each of the 149 women who had a
      singleton pregnancy progressing beyond 20 weeks of gestation following treatment,
      with regard to age, parity, height, husband's or partner's social class and
      smoking habits to account for common independent risk factors for adverse
      obstetric outcome and cervical intraepithelial neoplasia. MAIN OUTCOME MEASURES:
      Intention to conceive, number of pregnancies, gestation, low birthweight, mean
      birthweight, mode of delivery, and duration of labour. RESULTS: Out of a cohort
      of 1000 women who underwent LLETZ for the treatment of CIN, 653 women replied to
      a postal questionnaire. When asked up to 54 months after treatment, 130 women
      (19.9%) had become pregnant and 47 (7.2%) had tried to become pregnant. A total
      of 199 pregnancies from 178 women was identified from the cohort of women. For
      the 149 women from the case cohort, the mean birthweight was 3380 g compared with
      3373 g in the control group (P = 0.88). The incidence of low birthweights in
      pregnancies progressing to at least 37 weeks of gestation was 3.1% in the treated
      group, compared with 3.2% in the control group (P = 0.98). Following LLETZ, 9.4%
      of deliveries were preterm (< 37 weeks of gestation), compared with 5.0% in the
      control group (p = 0.12). There was no significant difference in mean gestation,
      mode of delivery, indication for caesarean section or duration of labour between
      the women who had undergone LLETZ and the controls. CONCLUSION: When socio
      epidemiological factors associated with the development of cervical
      intraepithelial neoplasia are controlled for, LLETZ does not appear to exert an
      independent adverse effect on subsequent pregnancy outcome.

PMID- 7632639
TI  - Endovaginal ultrasonography in the diagnosis of adenomyosis uteri: identifying
      the predictive characteristics.
AB  - OBJECTIVE: To evaluate prospectively the role of endovaginal ultrasonography in
      the diagnosis of adenomyosis and to identify predictive characteristics. SETTING:
      In Vitro Fertilisation Unit, Hammersmith Hospital. SUBJECTS: Fifty-six women with
      menorrhagia and dysmenorrhea. DESIGN: Endovaginal sonography was performed and
      uterine body morphometry and myometrial echogenicity were assessed. The
      sonographic suspicion of adenomyosis was scored high or low depending on the
      degree of uterine enlargement, uterine asymmetry not due to fibroids and
      heterogenicity of myometrial echoes. The sonographic diagnosis was compared
      either with the histological findings after hysterectomy (n = 34) or to the
      appearances on magnetic resonance imaging (n = 22). RESULTS: Adenomyosis was
      diagnosed in 28 patients: 15 by histology and 13 by magnetic resonance imaging.
      Endovaginal ultrasound demonstrated a sensitivity of 86%, a specificity of 50%, a
      positive predictive value of 86%, and a negative predictive value of 77%. Uterine
      morphometry alone did not predict adenomyosis: although the mean length of the
      longitudinal, anteroposterior and transverse axis was larger in uteri with,
      compared with those without, adenomyosis, this did not reach statistical
      significance. The uterine asymmetry ratio was 1.43 (SD 0.6) and 1.34 (SD 0.4) (P
      = 0.26) in uteri with and without adenomyosis, respectively, but in the presence
      of adenomyosis the mean posterior wall was significantly thicker than the mean
      anterior wall: 25.6 (SD 6.6) mm compared with 21.8 (SD 5.0) mm, P = 0.02.
      Therefore, adenomyosis was best predicted on the basis of ill-defined myometrial
      heterogeneity. However, leiomyomas and various echogenic shadows and artefacts
      often complicate subjective assessment of the myometrial echogenicity.
      CONCLUSION: Endovaginal sonography in symptomatic patients can be a sensitive but
      not a specific procedure for the diagnosis of adenomyosis.

PMID- 7632640
TI  - A randomised comparison over 8 months of 100 micrograms and 200 micrograms twice
      weekly doses of transdermal oestradiol in the treatment of severe premenstrual
      syndrome.
AB  - OBJECTIVE: To determine the efficacy of a 100 micrograms twice weekly dose of
      Estraderm TTS compared with a 200 micrograms dose in the treatment of severe PMS,
      and to determine the overall acceptability of the treatment. To determine the
      serum oestradiol levels produced by the two doses of Estraderm and to discover
      whether the lower dose suppresses ovulation. DESIGN: Main: randomised,
      prospective, comparative study. Subsidiary: cross-sectional and prospective.
      SETTING: Premenstrual syndrome clinic in teaching hospital. SUBJECTS: Women with
      severe PMS confirmed by prospective daily symptom recording. INTERVENTIONS:
      Estraderm TTS at a dose of either 100 or 200 micrograms twice weekly continuously
      with either dydrogesterone 10 mg or medroxyprogesterone acetate 5 mg, from day 17
      to day 26 of each cycle. MAIN OUTCOME MEASURES: Main: change in total,
      exponentially smoothed, average maximum score (total-ESAmax) of 10 common
      premenstrual syndrome symptoms derived from Trigg's trend analysis and patient
      satisfaction. Subsidiary: plasma oestradiol and day 21 progesterone levels.
      RESULTS: Main: no difference in change in total-ESAmax between Estraderm 100
      micrograms and 200 micrograms groups. Greater drop-out rate and greater incidence
      of side effects attributed to oestrogen in higher dosage group. Satisfaction rate
      of 45% to 57% at eight months. Subsidiary: 1. Mean (95% CI) oestradiol level of
      300 pmol/l (255 to 345) with Estraderm 100 micrograms and 573 (494 to 693) with
      Estraderm 200 micrograms; 2. Estraderm 100 micrograms suppresses mid-luteal
      progesterone from a mean (95% CI) of 35.5 (28.4 to 42.7) to 3.4 (2.4 to 4.5).
      CONCLUSIONS: Estraderm TTS 100 micrograms twice weekly is as effective as 200
      micrograms twice weekly in reducing symptom levels in severe premenstrual
      syndrome but is better tolerated. Estraderm 100 micrograms suppresses ovulation
      and results in a mean plasma oestradiol level similar to that observed in a
      spontaneous cycle.

PMID- 7632641
TI  - Working alongside a midwife-led care unit: what do obstetricians think?

PMID- 7632642
TI  - Outpatient vulval biopsy--a note of caution.

PMID- 7632643
TI  - Pre-eclampsia and the angiotensinogen gene.

PMID- 7632644
TI  - Echogenic foci in the fetal heart: a marker of chromosomal abnormality.

PMID- 7632645
TI  - Evaluation of Solcogyn: a paint-on preparation for the local treatment of
      cervical ectopy.

PMID- 7632646
TI  - Simple equipment to facilitate operative laparoscopic surgery (or how to avoid a
      spaghetti junction).

PMID- 7632647
TI  - Mallory-Weiss syndrome complicating pregnancy in a patient with scleroderma:
      diagnosis and management.

PMID- 7632648
TI  - Carbon dioxide embolism following diagnostic hysteroscopy.

PMID- 7632649
TI  - Misuse of lasers in gynaecology.

PMID- 7632650
TI  - Clustering of perinatal markers of birth asphyxia and outcome at age five years.

PMID- 7632651
TI  - Early abortion induction by a combination of mifepristone and oral misoprostol.

PMID- 7632653
TI  - Complications of the use of corticosteroids for the treatment of hyperemesis
      gravidarum.

PMID- 7632654
TI  - Complications of the use of corticosteroids for the treatment of hyperemesis
      gravidarum.

PMID- 7632652
TI  - The interpretation of midstream urine microscopy and culture results in women who
      present acutely to the labour ward.

PMID- 7632655
TI  - Complications of the use of corticosteroids for the treatment of hyperemesis
      gravidarum.

PMID- 7632656
TI  - Intravenous immunoglobulin in the prevention of recurrent miscarriage.

PMID- 7632657
TI  - Intravenous immunoglobulin in the prevention of recurrent miscarriage.

PMID- 7632658
TI  - Laparoscopic vaginal hysterectomy versus abdominal hysterectomy.

PMID- 7632659
TI  - Laparoscopic vaginal hysterectomy versus abdominal hysterectomy.

PMID- 7632660
TI  - Failure of laparoscopic uterine suspension to provide a lasting cure for
      uterovaginal prolapse.

PMID- 7632661
TI  - Models based on variable fractional digestion rates to describe ruminal in situ
      digestion.
AB  - Using a first-order model to describe ruminal in situ digestion implies that the
      rate of digestion is affected only by the quantity of potentially digestible
      substrate remaining. Other factors, like the microbial efficacy for digesting
      substrate, are assumed to be constant. However, microbes are not only the cause
      but also the result of digestion, being one of the digestion end-products. Two
      sigmoidal models (a logistic and a Gompertz-like model) were derived from a
      general digestion function in which the rate of digestion equals the product of
      the quantity of potentially digestible substrate remaining and a non-constant
      fractional rate of digestion (microbial efficacy function). The models were
      compared with a first-order model with a discrete lag time. The logistic model
      specifically accounted for the conversion of substrate mass to microbial mass,
      but did not describe microbial migration between the substrate and the ruminal
      fluid. In contrast, the Gompertz-like model assumed that the change in microbial
      efficacy was only time-dependent. There was little difference between models in
      estimates of scale parameters, but the asymptotic microbial efficacy was
      consistently higher for the logistic model than for the other models. Estimates
      of discrete lag time in the first-order model were biased towards obtaining
      values identical to the independent variable. Scale estimators appeared to be
      more robust than kinetic estimators. Lack-of-fit was present for most model-data
      set combinations. The similar patterns of residuals between models suggested that
      a four-parameter model may be insufficient to describe the data. It was concluded
      that if a four-parameter model is to be used, the model with a discrete lag time
      would be the least biologically appropriate.

PMID- 7632662
TI  - Responses to homeostatic signals in ractopamine-treated pigs.
AB  - The beta-agonist ractopamine (RAC) promotes protein deposition with little effect
      on fat deposition in the pig. To assess whether the lack of effect on fat
      deposition was due to changes in response to homeostatic signals, eight crossbred
      gilts (73 kg body weight (BW)) with venous catheters were used to examine plasma
      metabolite and hormone concentrations before and after intravenous injections of
      insulin and the beta 2-agonist fenoterol during dietary RAC (0 or 20 mg/kg)
      treatment. Pigs received intravenous challenges of insulin (1 microgram/kg BW) on
      days 3, 9 and 23 and fenoterol (2 micrograms/kg BW) on days 4, 10 and 24 of
      treatment. RAC was then withdrawn from the diet and insulin and fenoterol
      challenges were repeated 6 and 7 d later respectively. Blood samples for the
      determination of metabolite and hormone concentrations were taken at -30, -20, 
      10, -1, 2.5, 5, 10, 20, 30, 45, 60 and 120 min relative to the challenges.
      Dietary RAC decreased basal plasma insulin concentrations but had no effect on
      plasma glucose or non-esterified fatty acids (NEFA). Hypoglycaemic responses to
      insulin were not affected by RAC while the anti-lipolytic effects of insulin
      tended to be augmented. Dietary RAC decreased the lipolytic response to
      fenoterol, this being evident after 4 d treatment. Hypoglycaemic response to
      fenoterol was not changed whereas the hyperinsulinaemic response to fenoterol was
      attenuated by dietary RAC. Previous treatment with RAC did not influence basal
      hormone and metabolite concentrations or responses to homeostatic signals during
      the withdrawal period. While these results suggest little change in glucose
      metabolism, the de-sensitization of adipose tissue beta-adrenergic receptors is
      consistent with the observations that dietary RAC has little effect on the rate
      of fat deposition in the growing pig.

PMID- 7632663
TI  - The importance of dietary polyamines in cell regeneration and growth.
AB  - The polyamines putrescine, spermidine and spermine are essential for cell renewal
      and, therefore, are needed to keep the body healthy. It was previously believed
      that polyamines are synthesized by every cell in the body when required. However,
      in the present paper evidence is provided to show that, as in the case of the
      essential amino acids, the diet can supply sufficient amounts of polyamines to
      support cell renewal and growth. Systematic analysis of different foods was
      carried out and from the data obtained, the average daily polyamine consumption
      of British adults was calculated to be in the range 350-500 mumol/person per d.
      The major sources of putrescine were fruit, cheese and non-green vegetables. All
      foods contributed similar amounts of spermidine to the diet, although levels were
      generally higher in green vegetables. Meat was the richest source of spermine.
      However, only a part of the polyamines supplied by the diet is available for use
      by the body. Based on experiments with rats it was established that polyamines
      were readily taken up from the gut lumen, probably by passive diffusion, and were
      partly metabolized during the process of absorption. More than 80% of the
      putrescine was converted to other polyamines and non-polyamine metabolites,
      mostly to amino acids. The enzyme responsible for controlling the bioavailability
      of putrescine was diamine oxidase (EC 1.4.3.6). For spermidine and spermine,
      however, about 70-80% of the intragastrically intubated dose remained in the
      original form. Considering the limitations on bioavailability (metabolism and
      conversion), the amounts of polyamines supplied by the average daily diet in
      Britain should satisfy metabolic requirements.

PMID- 7632664
TI  - Effects of long-term protein excess or deficiency on whole-body protein turnover
      in sheep nourished by intragastric infusion of nutrients.
AB  - The effect of long-term dietary protein excess and deficit on whole-body protein
      N turnover (WBPNT) was examined in lambs nourished by intragastric infusions of
      nutrients. Ten sheep were given 500 mg N/kg metabolic weight (W0.75) per d from
      casein for 2 weeks and then either 50 (L), 500 (M) or 1500 (H) mg N/kgW0.75 per d
      for 6 weeks. Volatile fatty acids were infused at 500 kJ/kgW0.75 per d. Daily
      WBPNT was measured by continuous intravenous infusion of [1-13C]leucine 3 d
      before, and on days 2, 21 and 42 after the alteration in protein intake. Whole
      body protein-N synthesis (WBPNS) was calculated as the difference between WBPNT
      and the protein-N losses as urinary NH3 and urea. Whole-body protein-N
      degradation (WBPND) was then estimated from WBPNS minus protein gain determined
      from N balance. Fractional rates of WBPNS and WBPND were calculated against
      fleece-free body N content. WBPNS rates at the L, M and H intakes were
      respectively 35.1, 41.5 and 63.7 g/d (P < 0.001) on average over the 6 weeks and
      WBPND rates were 39.5, 41.1 and 56.8 g/d (P < 0.001). The fractional rates of
      WBPNS were 5.01, 6.37 and 7.73% per d (P < 0.001) while those of WBPND were 5.64,
      6.29 and 6.81% per d (P < 0.005) respectively. On days 2, 21 and 42, WBPNS rates
      at intake H were 54.0, 61.8 and 75.4 g/d (P = 0.03) respectively, and WBPND rates
      were 43.2, 56.4 and 70.9 g/d (P = 0.03); at intake L the amounts were 38.2, 34.2
      and 32.8 g/d for WBPNS (P = 0.003) and for WBPND were 43.4, 38.0 and 36.9 g/d (P
      = 0.016) respectively. There were no significant (P > 0.05) differences in
      fractional rates of WBPNS and WBPND with time at either the L or H intake. We
      concluded that absolute protein turnover was affected both by dietary protein
      intake and body condition while the fractional rate of turnover was predominantly
      influenced by intake.

PMID- 7632665
TI  - Modulation of oxidative stress by beta-carotene in chicken embryo fibroblasts.
AB  - The ability of beta-carotene to protect against oxidative stress in vitro was
      assessed. Primary cultures of chicken embryo fibroblasts (CEF) were oxidatively
      stressed by exposure to paraquat (PQ). Activities of the antioxidant enzymes
      superoxide dismutase (SOD; EC 1.15.1.1), catalase (CAT; EC 1.11.1.6) and
      glutathione peroxidase (GSH-Px; EC 1.11.19) were measured as indices of oxidative
      stress. CEF incubated with 0.25 mM-PQ for 18 h exhibited increased SOD and CAT
      activities and decreased GSH-Px activity compared with the control (P < 0.001).
      Incorporation of added beta-carotene (0.1 microM) into 0.25 mM-PQ-treated CEF
      returned SOD activity to that seen in non-PQ-treated cells. beta-Carotene (0.1
      microM) reduced the CAT activity from that seen in PQ-treated cells and returned
      the GSH-Px activity to its control value thus protecting the cells against PQ
      induced oxidative stress. However, at higher concentrations of beta-carotene (10
      microM), SOD and CAT activities increased significantly (P < 0.001) relative to
      non-PQ-treated cells and GSH-Px activity decreased relative to its control value.
      Similar trends were observed when CEF grown in beta-carotene-enriched media (0.1
      10 microM) were oxidatively stressed by exposure to 0.25 mM-PQ for 18 h.

PMID- 7632666
TI  - Effect of the lipase inhibitor orlistat and of dietary lipid on the absorption of
      radiolabelled triolein, tri-gamma-linolenin and tripalmitin in mice.
AB  - Orlistat, a selective inhibitor of gastrointestinal lipases, was used to
      investigate triacylglycerol absorption. Using mice and a variety of emulsified
      dietary lipids we found that the absorption of radiolabelled tripalmitin
      (containing the fatty acid 16:0), but not of triolein (18:1n-9) or tri-gamma
      linolenin (18:3n-6), was incomplete from meals rich in esterified palmitate.
      Further, the absorption of radiolabelled tri-gamma-linolenin, from both saturated
      and unsaturated dietary triacylglycerols, was 1.3- to 2-fold more potently
      inhibited by orlistat than that of triolein and tripalmitin. These radiolabelled
      triacylglycerols, which have the same fatty acid in all three positions, may not
      always be accurate markers of the absorption of dietary triacylglycerols.
      Orlistat was more effective at inhibiting the absorption of radiolabelled
      triacylglycerols with which it was codissolved than those added separately, which
      indicates that equilibration between lipid phases in the stomach may not always
      be complete. The saturation of the dietary lipid had little or no effect on the
      potency of orlistat. Orlistat provides a novel approach for studying the role of
      triacylglycerol hydrolysis in the overall process of triacylglycerol absorption.

PMID- 7632667
TI  - High tin intake reduces copper status in rats through inhibition of copper
      absorption.
AB  - The mechanism underlying the reduced Cu status in rats fed on a high-Sn diet was
      investigated. Male rats aged 4 weeks were fed ad lib. on purified diets
      containing either 1 or 100 mg Sn/kg and demineralized water for a period of 4
      weeks. The high-Sn diet had no effect on feed intake, body-weight gain or weight
      of liver and kidney but significantly reduced Cu concentrations in plasma, liver
      and kidney. Biliary Cu excretion was decreased significantly in rats fed on the
      high-Sn diet. Apparent Cu absorption (Cu intake-faecal Cu) was not affected by
      the high-Sn diet, but the estimate of true Cu absorption (Cu intake-(faecal Cu
      biliary Cu)) was significantly reduced. We conclude that high Sn intake reduces
      Cu status in rats through inhibition of Cu absorption. The decreased biliary Cu
      excretion observed on the high-Sn diet is a result of the reduced Cu absorption.

PMID- 7632668
TI  - Effects of intestinal resection, cholecalciferol and ascorbic acid on iron
      metabolism in rats.
AB  - The effect of dietary supplementation with ascorbic acid or cholecalciferol on Fe
      utilization was studied using the metabolic balance technique, in rats in which
      50% of the distal small intestine was removed, or in which the mid small
      intestine was transected and reanastomosed (controls). Three different diets were
      used. The first (basal diet) contained (g/kg dry wt): protein (casein + 50 mg D,L
      methionine/g) 120 and fat (medium-chain triacylglycerols, olive oil and sunflower
      oil, in equal parts) 40. The other diets were obtained by adding ascorbic acid
      (150 mg/kg diet) or cholecalciferol (0.4 mg/kg diet) to the basal diet. Apparent
      digestibility coefficient (ADC) and Fe retention were significantly lower in
      resected animals than in their respective control groups (transected rats).
      However, the addition of ascorbic acid or cholecalciferol to the basal diet
      increased the ADC and Fe retention in both transected and resected rats. Five
      weeks after surgery, resection also resulted in a reduced concentration of Fe in
      the sternum, but did not reduce the concentration of haemoglobin or serum Fe
      total Fe-binding capacity or the concentration of Fe in liver, testes, femur or
      muscle (longissimus dorsi). Supplementation with ascorbic acid increased serum Fe
      concentration, while the concentration of Fe in muscle was reduced by
      supplementation with both ascorbic acid and cholecalciferol. Neither
      supplementation had any effect on the Fe concentration in other tissues, on
      haemoglobin concentration or plasma total Fe-binding capacity. Thus,
      supplementation with ascorbic acid or with cholecalciferol increased Fe
      absorption and reduced the concentration of Fe in muscle.

PMID- 7632669
TI  - Vitamin D deficiency: a concern in pregnant Asian women.
AB  - Vitamin D status of Asian mothers in Cardiff was investigated during early
      pregnancy and at the time of the birth of their babies, using serum parathyroid
      hormone (PTH). Median values in Asian (n 32) and Caucasian (n 63) mothers in
      early pregnancy were 1.56 and 0.81 pmol/l respectively. PTH levels from a
      separate sample of nineteen Asian and twenty-five Caucasian mothers at the time
      of birth were 3.0 and 2.20 pmol/l respectively. Altogether twelve Asian and two
      Caucasian women had elevated PTH. All Asian women who had high PTH values also
      had a very low serum 25-hydroxycholecalciferol level (25OHD). All samples were
      taken from women with no significant medical history and normal obstetric
      history. These findings suggest that subclinical vitamin D deficiency is still a
      cause for concern in Asian women. More active measures need to be taken to
      implement current recommendations to improve their vitamin D intake in pregnancy.

PMID- 7632670
TI  - Retinoid metabolism in human leucocytes.
AB  - Leucocytes from subjects from 0 to 80 years old were separated into mononuclear
      and granulocyte fractions and the retinoids and retinoid-binding fractions were
      examined. Both leucocyte fractions were found to contain retinol, retinoic acid
      and an additional retinoid; retinoic acid comprised 40% of retinoids in some
      samples. The protein fractions containing retinoids included a 200 kDa protein
      and several 14-18 kDa proteins. Plasma concentrations of retinol changed little
      with increasing age. In contrast, leucocyte concentrations of retinoids and
      retinoid-binding proteins increased quadratically with age. However, in
      granulocytes from young children retinoids were almost undetectable.

PMID- 7632671
TI  - Formation of complexes between polyvinyl pyrrolidones or polyethylene glycols and
      tannins, and their implication in gas production and true digestibility in in
      vitro techniques.
AB  - Various tannin-complexing agents have been used to study the potential adverse
      effects of tannins on rumen metabolism. Using a method based on turbidity
      formation, the binding of various tannin-complexing agents (polyvinyl
      polypyrrolidone (PVPP), polyethylene glycol (PEG) of molecular weights 2000 to
      35,000, and polyvinyl pyrrolidone (PVP) of molecular weight 10,000, 40,000 and
      360,000) to tannins (tannic acid, purified tannins from quebracho (Aspidosperma
      quebracho) and leaves of trees and shrubs (Acioa barteri, Dichostachys cinerea,
      Guiera senegalensis, Piliostigma reticulatum)) was investigated at different pH
      values. The binding of all the tannins with PVPP was highest at pH 3-4 and lowest
      at pH 7. For all the pH range (3-7) studied, the binding of PEG was higher than
      that of PVP. For all the tannins except tannic acid, the binding to PVP was the
      same from pH 4.7 to 7. Similar results were observed for the PEG of molecular
      weight 6000 or higher for all the tannins except quebracho tannins for which the
      binding increased as the pH increased from 3 to 7. The binding with PEG 2000
      decreased to a greater extent as the pH reached near neutral and for PEG 4000
      this decrease was slightly lower. Addition of these tannin-complexing agents to
      the in vitro gas system resulted in higher gas production from tannin-rich feeds
      (increase varied from 0 to 135%). The PEG were the most effective followed by PVP
      and PVPP. The PEG 35,000 was least effective. The efficiency of other PEG was
      similar. The PEG 6000 was preferred to PEG 2000 or 4000 as its binding to tannins
      was higher at near neutral pH values. The gas production increased with an
      increase in the amount of PEG 6000 up to 0.6 g/40 ml rumen-fluid-containing
      medium containing 0.5 g tannin-rich feed, beyond which no increase was observed.
      The percentage increase in gas value at 24 h fermentation correlated
      significantly with tannin values, the highest correlation (r 0.95) being with
      protein precipitation capacity of tannins. The increase in gas production was
      associated with higher production of short-chain fatty acids with little change
      in their molar proportions, suggesting an increase in organic matter
      digestibility by inclusion of the PEG in tannin-rich feeds. However, apparent and
      true digestibilities were lower on addition of the PEG, due to the presence of
      PEG-tannin complexes in the residues. The use of this bioassay (percentage
      increase in gas production in the presence of PEG 6000) along with other tannin
      assays would provide a better insight into the nutritional significance of
      tannins.

PMID- 7632672
TI  - Cytochrome c oxidase: biphasic kinetics result from incomplete reduction of
      cytochrome a by cytochrome c bound to the high-affinity site.
AB  - The electron-transfer kinetics of cytochrome c oxidase were probed by measuring
      the reduction levels of bound cytochrome c, cytochrome a, and cytochrome a3
      during steady-state turnover. Our experimental approach was to measure these
      reduction levels as a function of (1) the rate of electron input into tightly
      bound cytochrome c by varying the concentration of TMPD (N,N,N',N'-tetramethyl-p
      phenylenediamine) and/or cytochrome c and (2) the rate of electron efflux out of
      cytochrome a (true Kcat) by changing the detergent surrounding cytochrome c
      oxidase. In most detergent environments, the rate of electron input into
      cytochrome c is not faster than the rate of electron efflux from cytochrome a.
      The relatively slow rate of electron input results in incomplete reduction of
      both cytochrome a and cytochrome c bound a the high-affinity site unless Kcat is
      very slow. When the high-affinity site is saturated with cytochrome c, the steady
      state reduction level of cytochrome a defines Vmax,1, which is the maximum
      velocity of the high-affinity phase. The remaining fractional oxidation level of
      cytochrome a determines Vmax,2, the maximum velocity of the low-affinity phase.
      Therefore, it is the sum Vmax,1 + Vmax,2 which defines the maximum rate of
      electron transfer between cytochrome a and the bimetallic center, i.e., Kcat. We
      also were able to evaluate the true Kcat of cytochrome c oxidase in each
      detergent environment directly from the steady-state reduction levels without any
      of the complications introduced by the analysis of the polarographic kinetic
      data.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7632673
TI  - Kinetics and mechanism for the binding of HCN to cytochrome c oxidase.
AB  - The kinetics of cyanide binding to cytochrome c oxidase were systematically
      studied as a function of [HCN], [oxidase], pH, ionic strength, temperature, type
      and concentration of solubilizing detergent, and monomer-dimer content of
      oxidase. On the basis of these results a minimum reaction mechanism is proposed
      in which the spectrally visible rapid and slow cyanide binding reactions are two
      consecutive first-order reactions, not parallel reactions with different
      conformers of cytochrome c oxidase. The fast reaction (k'obs) follows saturation
      type kinetics to form an HCN complex that subsequently undergoes a slow reaction
      (k'obs). The fast k'obs reaction is independent of ionic strength but is strongly
      dependent upon pH. Two pK values were evaluated from the bell-shaped rate versus
      pH profile; one is due to an ionizable group on the protein (pKa = 7.45), while
      the other is that of HCN (pKHCN = 9.15). Therefore, oxidase is reactive toward
      HCN only when the group on the protein is unprotonated. The slow k'obs reaction
      is not a reaction of oxidase with either CN- or HCN; in fact, the product formed
      by the fast k'obs reaction, the oxidase-HCN complex, still undergoes the slow k"
      process even if all of the excess KCN is removed. The apparent rate constant of
      the slower phase (k"obs) is independent of all the variations done in this study,
      and it probably corresponds to either a slow conformational change in the protein
      or a change in ligand coordination at one of the metal centers after HCN binds to
      the bimetallic center of oxidase. Based upon the bell-shaped pH dependence of the
      fast phase and the pH independence of the slow phase, the mechanism also predicts
      that a single conformer of cytochrome c oxidase can exhibit either monophasic or
      biphasic cyanide binding kinetics depending upon the pH. At either very low or
      very high pH, the two rates become comparable in magnitude, which makes the
      reaction appear to be monophasic even though both reactions still occur. The
      amount of monomeric or dimeric oxidase only slightly affects the magnitude of
      k'obs and k"obs values, and both processes are clearly present in both types of
      oxidase.

PMID- 7632674
TI  - Specific degradation of the D1 protein of photosystem II by treatment with
      hydrogen peroxide in darkness: implications for the mechanism of degradation of
      the D1 protein under illumination.
AB  - The D1 protein of the photosystem II (PSII) reaction center has a rapid turnover
      and is specifically degraded under illumination in vivo. When isolated PSII
      membranes were treated in darkness with 10 mM hydrogen peroxide (H2O2), an active
      form of oxygen that is generated at the acceptor side of PSII under illumination,
      proteins of the PSII reaction center were specifically damaged in almost the same
      way as observed under illumination with strong light. The D1 protein and, to a
      lesser extent, the D2 protein were degraded to specific fragments, and cross
      linked products (the covalently linked adduct of the D1 protein and the alpha
      subunit of cytochrome b559 and the heterodimer of the D1 and D2 proteins) were
      generated concomitantly. The site of cleavage of the D1 protein that gave rise to
      a major fragment of 22 kDa was located in the loop that connects membrane
      spanning helixes IV and V. Treatment with H2O2 caused the same damage to proteins
      in isolated thylakoids and in core complexes that contained the non-heme iron at
      the acceptor side, but not in isolated reaction centers depleted of the iron.
      From these observations and the effects of reagents that are known to interact
      with the non-heme iron, it is suggested that the damage to proteins is caused by
      oxygen radicals generated by the non-heme iron in the Fe(II) state in a reaction
      with H2O2. It is proposed, moreover, that a similar mechanism is operative during
      the selective and specific degradation of the D1 protein under illumination.

PMID- 7632675
TI  - Distribution and dynamics of mouse sperm surface galactosyltransferase:
      implications for mammalian fertilization.
AB  - It has been proposed that a mouse sperm surface beta-1,4-galactosyltransferase
      functions as a receptor for the zona pellucida during fertilization. In this
      paper we used two monovalent fluorescent probes specific for
      galactosyltransferase: a trinitrophenylated derivative of UDP-galactose and
      rhodaminated alpha-lactalbumin. We found that galactosyltransferase was initially
      present over the posterior head of acrosome-intact sperm but became progressively
      localized to the plasma membrane overlying the acrosomal region after it was
      cross-linked with an anti-galactosyltransferase polyclonal antibody. Labeled
      mouse sperm that were treated with the calcium ionophore A23187 revealed that
      galactosyltransferase remained on the posterior head after acrosomal exocytosis.
      However, if galactosyltransferase was first cross-linked and redistributed with
      antibody and then acrosome reacted with A23187, all head fluorescence was lost.
      In addition, although anti-galactosyltransferase antibody induced a surface
      redistribution, it did not, by itself, lead to the release of acrosin, the
      endpoint of the acrosome reaction. Finally, using the technique of fluorescence
      recovery after photobleaching, we found that, in the absence of bivalent
      antibody, mouse sperm surface galactosyltransferase exhibited 40-50% recovery
      with a high diffusion coefficient on the anterior head (5-8 x 10(-9) cm2/s)
      approximately 2 times greater than on the posterior head (2-4 x 10(-9) cm2/s).
      When galactosyltransferase was cross-linked and redistributed to the anterior
      head using the bivalent antibody, the mobile fraction decreased to 20-30% with no
      significant change in the diffusion coefficient.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7632676
TI  - Role of gpFI protein in DNA packaging by bacteriophage lambda.
AB  - One of the final steps in the assembly of bacteriophage lambda is the excision of
      a single genome from a concatemeric DNA precursor and insertion of this monomer
      into a preformed capsid. Terminase enzymes are common to all of the double
      stranded DNA phages, and in lambda this enzyme is responsible for both excision
      of a genome monomer from the concatemer and its insertion into the pro-capsid. We
      have previously demonstrated that the endonuclease activity of lambda terminase
      (cos-cleavage) was stoichiometric with enzyme and postulated that this was due to
      formation of a stable, postcleavage enzyme.DNA intermediate (complex I) (Tomka &
      Catalano, 1993b). Bacteriophage lambda gpFI protein is required for efficient
      assembly of the virus, and current models suggest that this protein increases the
      rate of pro-capsid binding to complex I. We show here that gpFI markedly
      stimulates cos-cleavage by lambda terminase, even in the absence of viral pro
      capsids. Importantly, the observed increase in nicking activity did not result
      from an increase in the rate of cos-cleavage, but rather by an increase in
      turnover by the enzyme. These data suggest that gpFI destabilizes complex I, thus
      allowing terminase release from cos and catalytic turnover by the enzyme. The
      implications of these results with respect to terminase assembly onto viral DNA,
      nicking of the duplex, and subsequent translocation during packaging are
      discussed.

PMID- 7632677
TI  - Role of calcium(II) ions in the recognition of coagulation factors IX and X by
      IX/X-bp, an anticoagulant from snake venom.
AB  - IX/X-bp, an anticoagulant protein isolated from the venom of the habu snake
      Trimeresurus flavoviridis, has a structure homologous to the carbohydrate
      recognition domains of C-type (Ca(2+)-dependent) animal lectins, and it binds to
      the gamma-carboxyglutamic acid (Gla) domains of coagulation factors IX and X in a
      Ca(2+)-dependent fashion. In the present study, we elucidated the role of Ca2+
      ions in this binding. The binding of 125I-labeled IX/X-bp to both coagulation
      factors required about 1 mM Ca2+ ions in this at pH 7.5. A decrease in the pH to
      6.5 had a striking negative effect on the binding, and the Ca(2+)-requirement
      curve was shifted rightward. We investigated the binding of Ca2+ ions to IX/X-bp
      directly by equilibrium dialysis and identified two independent binding sites
      with different affinities. At pH 7.5, the apparent Kd values for these sites were
      25 and 200 microM, respectively. When the pH was decreased to 6.5, the affinity
      of the high-affinity binding site was reduced only slightly but that of the low
      affinity site was reduced considerably. Moreover, it was evident from
      observations of Ca(2+)-induced changes in the intrinsic fluorescence that IX/X-bp
      underwent a conformational change upon binding of Ca2+ ions.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7632678
TI  - Oligonucleotides containing G.A pairs: effect of flanking sequences on structure
      and stability.
AB  - Sixteen oligodeoxyribonucleotides, 5'd(GXGAYC)3', X and Y = G, A, C, or T, have
      been synthesized and studied by UV melting and 1H and 31P NMR methods. By varying
      X and Y, the sixteen resulting oligonucleotides can theoretically form 10
      duplexes with all possible Watson-Crick base pairs flanking the center two G.A
      base pairs. Two-dimensional 1H NMR data on 5'd(GCGAGC)3' revealed that the center
      bases G and A pair through G amino hydrogen bonding and that the two consecutive
      G.A pairs form excellent purine-purine stacks. The concurrent appearance of one
      or more upfield-shifted imino proton peaks (approximately 10.5 ppm) and both
      upfield- and downfield- shifted 31P signals (approximately -2 and approximately 
      5.1 ppm) was a unique characteristic in imino 1H and 31P NMR spectra and was used
      as a conformational probe for this type of G.A pairs. Using this probe, seven out
      of 10 duplexes of 5'GXGAYC3' were found to adopt the G.A base pairing with G
      amino proton bonding and G to G and A to A base stacking. Three were in the group
      comprising 5'pyrimidine-GA-purine3', and four were in the group comprising
      5'purine-GA-purine3'/5'pyrimidine-GA-pyrimidine3'. The G.A pairs in 5'purine-GA
      pyrimidine3' adopted a totally different conformation. Thermodynamic analysis
      indicated that duplexes in the 5'pyrimidine-GA-purine3' group were more stable
      than the duplexes in the 5'purine-GA-pyrimidine3' group. Overall, G.C base pairs
      were preferred as neighbors to this type of G.A pairs.

PMID- 7632680
TI  - Pulsed electron paramagnetic resonance studies of the lysine 2,3-aminomutase
      substrate radical: evidence for participation of pyridoxal 5'-phosphate in a
      radical rearrangement.
AB  - The role of pyridoxal 5'-phosphate (PLP) in the radical-mediated amino group
      migration catalyzed by lysine 2,3-aminomutase from Clostridia SB4 has been
      investigated by electron spin echo envelope modulation (ESEEM) spectroscopy. This
      pulsed electron paramagnetic resonance (EPR) method was used to estimate the
      distance between the unpaired electron in the alpha-radical of beta-lysine, a
      steady-state intermediate in the reaction, and deuterium at the C4' position of
      the cofactor, PLP. [4'-2H]PLP was synthesized and exchanged into the enzyme. The
      steady-state radical was generated in the labeled samples and in samples with
      unlabeled PLP by addition of L-lysine.H2SO4 to activated enzyme. ESEEM spectra of
      the samples prepared with [4'-2H]PLP exhibited distinctive low-frequency
      modulations that were not present in spectra of matched samples with unlabeled
      PLP. Fourier transformation of the modulations yielded a prominent doublet signal
      centered about the Larmor frequency of deuterium. The magnitude of the doublet
      splitting of the 2H ESEEM signal exhibited angle selection across the CW EPR
      powder pattern. The observed angle selection, as well as simulation of the time
      domain spectra, indicated that the doublet splitting was due to the combined
      effects of the 2H hyperfine and nuclear quadrupole interactions. The influences
      of the quadrupole interaction and of isotropic and dipolar hyperfine interactions
      were explored by simulations of the ESEEM spectra. The analysis indicates a
      distance of < 3.5 A between the 2H at C4' of PLP and the radical center at C
      alpha lysine. The data are most compatible with an aldimine linkage between PLP
      and the beta-nitrogen of beta-lysine.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7632679
TI  - Gene cloning, expression, and characterization of the Sac7 proteins from the
      hyperthermophile Sulfolobus acidocaldarius.
AB  - The genes for two Sac7 DNA-binding proteins, Sac7d and Sac7e, from the extremely
      thermophilic archaeon Sulfolobus acidocaldarius have been cloned into Escherichia
      coli and sequenced. The sac7d and sac7e open reading frames encode 66 amino acid
      (7608 Da) and 65 amino acid (7469 Da) proteins, respectively. Southern blots
      indicate that these are the only two Sac7 protein genes in S. acidocaldarius,
      each present as a single copy. Sac7a, b, and c proteins appear to be carboxy
      terminal modified Sac7d species. The transcription initiation and termination
      regions of the sac7d and sac7e genes have been identified along with the promoter
      elements. Potential ribosome binding sites have been identified downstream of the
      initiator codons. The sac7d gene has been expressed in E. coli, and various
      physical properties of the recombinant protein have been compared with those of
      native Sac7. The UV absorbance spectra and extinction coefficients, the
      fluorescence excitation and emission spectra, the circular dichroism, and the two
      dimensional double-quantum filtered 1H NMR spectra of the native and recombinant
      species are essentially identical, indicating essentially identical local and
      global folds. The recombinant and native proteins bind and stabilize double
      stranded DNA with a site size of 3.5 base pairs and an intrinsic binding constant
      of 2 x 10(7) M-1 for poly[dGdC].poly[dGdC] in 0.01 M KH2PO4 at pH 7.0. The
      availability of the recombinant protein permits a direct comparison of the
      thermal stabilities of the methylated and unmethylated forms of the protein.
      Differential scanning calorimetry demonstrates that the native protein is
      extremely thermostable and unfolds reversibly at pH 6.0 with a Tm of
      approximately 100 degrees C, while the recombinant protein unfolds at 92.7
      degrees C.

PMID- 7632681
TI  - Characterization of metal binding by a designed protein: single ligand
      substitutions at a tetrahedral Cys2His2 site.
AB  - The tetrahedral Cys2His2 Zn(II)-binding site in the de novo designed protein Z
      alpha 4 [Regan, L., & Clarke, N. D. (1990) Biochemistry 29, 10878] has been
      studied by independently mutating each of the metal-binding ligands to alanine.
      The contribution of each ligand to the geometry and affinity of metal binding has
      been characterized using Co(II), Zn(II), and Cd(II). The results indicate that
      all four ligands contribute to high-affinity metal binding in Z alpha 4. Two of
      the four metal-site mutants retain the tetrahedral Zn(II)-binding geometry of Z
      alpha 4, with one water molecule presumed to bind in the vacant ligand position.
      These mutants provide the first examples of a demonstrated de novo tetrahedral
      three-coordinate site designed into a protein and as such are a first step toward
      the design of catalytic rather than structural Zn(II) sites. One of the metal
      site mutants binds Zn(II) with either tetrahedral four-coordinate or five
      coordinate geometry, while the last ligand-to-alanine substitution abolishes
      tetrahedral binding. The importance of ligand type for metal-binding in Z alpha 4
      was investigated by characterizing two ligand-swap mutants in which a cysteine
      residue was replaced with a histidine. In both cases, tetrahedral metal binding
      was lost. Collectively, these results affirm the strategy used to design Z alpha
      4 by showing that all designed liganding residues are participating in metal
      binding, and by suggesting that the tetrahedral geometry of the binding site is
      perturbed when the designed side chain ligands are replaced with alternate
      ligands.

PMID- 7632682
TI  - Two conformations of the catalytic site in the aa3-type cytochrome c oxidase from
      Rhodobacter sphaeroides.
AB  - Resonance Raman spectra of the carbon monoxy derivative of the aa3-type
      cytochrome c oxidase from Rhodobacter sphaeroides show two distinct Fe-CO
      stretching modes (519 and 493 cm-1) at room temperature. The frequency of the
      mode at 519 cm-1 coincides with that of other terminal oxidases at neutral pH.
      Two C-O stretching modes, one at 1966 cm-1 and one at 1955 cm-1, are also found.
      The splitting of the C-O stretching mode is consistent with the FTIR spectra of
      cytochrome c oxidases at cryogenic temperatures in which two different
      conformations (alpha and beta) of the catalytic site of the enzyme are present.
      The splitting of both the Fe-CO and C-O stretching modes under our conditions
      indicates that these two forms of the enzyme are also present at room
      temperature, and with the additional information on the Fe-CO modes provided
      here, a structural origin for the two forms may be postulated. The alpha-form has
      the same general structure of the active site as mammalian oxidase, a structure
      in which the copper atom that is the part of the Fe-CuB binuclear site interacts
      strongly with the bound CO. We postulate that the copper atom exerts a strong
      polar or steric effect on the heme-bound CO, resulting in either compression of
      the Fe-CO bond or distortion of the Fe-CO moiety.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7632684
TI  - X-ray structure of two complexes of the Y143F flavocytochrome b2 mutant
      crystallized in the presence of lactate or phenyl lactate.
AB  - Flavocytochrome b2 is a flavohemo enzyme localized in the intermembrane space of
      yeast mitochondria, where it catalyzes the electron transfer from its substrate,
      L-lactate, to cytochrome c. We have obtained crystals of a flavocytochrome b2
      mutant, Y143F, which are isostructural with those of the native recombinant
      enzyme [Tegoni, M., & Cambillau, C. (1994) Protein Sci.3, 303-314]. These
      crystals were grown under similar conditions to those used to obtain the
      recombinant enzyme, but in the presence of phenyl lactate or lactate. We report
      here on the structural analysis of the two complexes of flavocytochrome b2 with
      the reaction products at 2.9 A resolution. In both structures, the Phe143 phenyl
      ring keeps the same position as that of the phenolic ring of Tyr143 in both the
      native recombinant and in the native wild-type enzymes. The product of the
      reaction, phenyl pyruvate or pyruvate, is present at the active site of both
      subunits, and not only in subunit 2 as observed in the wild-type structure [Xia,
      Z.-X., & Mathews, F.S. (1990) J. Mol. Biol. 212, 837-863]. The number of
      interactions between the FMN and the heme domain is considerably lower in the
      Y143F mutant than in the native proteins. The latter finding strongly supports
      the hypothesis that the main role of Tyr143 in the native proteins. The latter
      findings strongly supports the hypothesis that the main role of Tyr143 in the
      native protein probably consists in establishing a hydrogen bond with the heme
      [Xia, Z.-X., & Mathews, F.S. (1990) J. Mol. Biol. 212, 837-863]. This interaction
      appears to be essential for the two domains to approach each other suitably so
      that the intramolecular electron transfer can occur.

PMID- 7632683
TI  - Solution structure of the DNA binding domain of HIV-1 integrase.
AB  - The solution structure of the DNA binding domain of HIV-1 integrase (residues 220
      270) has been determined by multidimensional NMR spectroscopy. The protein is a
      dimer in solution, and each subunit is composed of a five-stranded beta-barrel
      with a topology very similar to that of the SH3 domain. The dimer is formed by a
      stacked beta-interface comprising strands 2, 3, and 4, with the two triple
      stranded antiparallel beta-sheets, one from each subunit, oriented antiparallel
      to each other. One surface of the dimer, bounded by the loop between strands beta
      1 and beta 2, forms a saddle-shaped groove with dimensions of approximately 24 x
      23 x 12 A in cross section. Lys264, which has been shown from mutational data to
      be involved in DNA binding, protrudes from this surface, implicating the saddle
      shaped groove as the potential DNA binding site.

PMID- 7632685
TI  - Three-dimensional solution structure of the oxidized high potential iron-sulfur
      protein from Chromatium vinosum through NMR. Comparative analysis with the
      solution structure of the reduced species.
AB  - The NMR solution structure of the oxidized HiPIP from Chromatium vinosum has been
      solved. Despite the fact that the protein is paramagnetic, 85% of the 1H and 80%
      of the 15N signals have been assigned. Through 1537 NOEs, out of which 1142 were
      found to be relevant for the structure determination, a family of structures has
      been obtained by distance geometry calculations. These structures have then been
      subjected to restrained energy minimization (REM) and restrained molecular
      dynamics (RMD) calculations in vacuum. Finally, the mean structure of the RMD
      family has been treated through RMD in water. The RMSD values for the backbone
      and heavy atoms within the RMD family are 0.57 +/- 0.14 and 1.08 +/- 0.16 A,
      respectively. These values together with other parameters indicate that the
      structure is of good quality and as good as the structure of the reduced protein.
      The RMDw structures of the reduced and oxidized proteins are different beyond the
      experimental indetermination. The set of constraints for the reduced and oxidized
      forms have been used to treat the available X-ray structure by RMD in water. The
      two structures generated in this way are quite similar to their respective
      solution structures, thus confirming that the experimental constraints are
      capable of yielding two different structures from the same starting structural
      model. This is the first time that independently determined solution structures
      of two redox states of a paramagnetic protein are available. Differences between
      them and the X-ray structure are discussed.

PMID- 7632686
TI  - Structural characterization of the interaction between a pleckstrin homology
      domain and phosphatidylinositol 4,5-bisphosphate.
AB  - The pleckstrin homology (PH) domain is a protein module of approximately 100
      amino acids that is found in several proteins involved in signal transduction
      [for a recent review, see Gibson et al. (1994) Trends Biochem. Sci. 19, 349-353].
      Although the specific function of the PH domain has not yet been elucidated, many
      of the proteins which contain this domain associate with phospholipid membranes,
      and PH domains have been shown to bind to phosphatidylinositol 4,5-bisphosphate
      (PIP2) [Harlan et al. (1994) Nature 371, 168-170] and the beta gamma subunits of
      G-proteins [Touhara et al. (1994) J. Biol. Chem. 269, 10217-10220]. We have
      postulated that pleckstrin homology domains may be important for the
      translocation of proteins to the membrane by an interaction with the negatively
      charged head group of phospholipids. Here we show the importance of three
      conserved lysine residues for binding to PIP2 by site-directed mutagenesis. These
      results should aid future site-directed mutagenesis studies in probing the
      function of PIP2-PH domain interactions in the various proteins containing this
      module. In addition, we examine the specificity of this binding and illustrate
      the importance of charge--charge interactions in PIP2-PH domain complex formation
      from binding experiments involving PIP2 analogs.

PMID- 7632687
TI  - Response of rubredoxin from Pyrococcus furiosus to environmental changes:
      implications for the origin of hyperthermostability.
AB  - The bases of the hyperthermostability of rubredoxin from Pyrococcus furiosus
      (RdPf) have been probed by structural perturbations induced by solution pH and
      ionic strength changes. Comparison of the solution behavior at pH 7 and pH 2, as
      probed by far- and near-UV circular dichroism, Trp fluorescence emission, 1
      anilinonaphthalene-8-sulfonate (ANS) binding, and NMR spectroscopy, reveals the
      presence of only minimal structural variations at room temperature. At pH 2, the
      protein displays a surprising nearly native-like behavior at high ionic strength
      while, at low ionic strength, it is capable of strongly binding the hydrophobic
      probe ANS. All the secondary and tertiary structural features, including the
      environment of the hydrophobic core, appear to be intact regardless of pH and
      ionic strength. The apparent "melting" or denaturation temperature at pH 2,
      however, is 42 degrees C lower than at pH 7. This is attributed to the
      perturbation of many electrostatic interactions, including the disruption of all
      the ion pairs, which is complete at pH 2, as indicated by electrometric pH
      titrations. The implications of these findings for the origins of the
      hyperthermostability of rubredoxin are discussed.

PMID- 7632688
TI  - Na,K-ATPase inhibitors from bovine hypothalamus and human plasma are different
      from ouabain: nanogram scale CD structural analysis.
AB  - The specific, high affinity binding of plant-derived digitalis glycosides by the
      mammalian sodium and potassium transporting adenosine triphosphatase (Na,K
      ATPase, or sodium pump), a plasma membrane enzyme with critical physiological
      importance in mammalian tissues, has raised the possibility that a mammalian
      analog of digitalis might exist. We previously isolated and structurally
      characterized from bovine hypothalamus a novel isomer of the plant glycoside,
      ouabain, which differs structurally only in the attachment site and/or the
      stereochemistry of the steroid moiety [Tymiak et al. (1993) Proc. Natl. Acad.
      Sci. U.S.A. 90, 8189-8193]. Hamlyn and co-workers reported a molecule purified
      from human plasma which by mass spectrometry could not be distinguished from
      plant ouabain [Hamlyn et al. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 6259-6263].
      Since rhamnoside cardiotonic steroids are not known as natural products from
      mammalian sources, it became important to compare these two pure isolates to
      determine if the same or structurally distinct compounds has been found. Our
      results indicate that the human and bovine Na,K-ATPase-inhibitors are identical,
      but different from plant ouabain. This supports the notion that the human sodium
      pump may be under specific physiological regulation by a mammalian analog of the
      digitalis glycosides.

PMID- 7632690
TI  - Physical and conformational properties of synthetic idealized signal sequences
      parallel their biological function.
AB  - Transported proteins often contain an extension sequence called the signal
      peptide. The alkaline phosphatase (PhoA) signal sequence represents a typical
      signal peptide for comparison to idealized sequences both in vivo and in vitro.
      We have designed a series of idealized signal sequences which vary in amino
      terminal charge and core region hydrophobicity with minimal variation in amino
      acid composition. The idealized core regions contain different proportions of
      leucine and alanine residues, effectively producing hydrophobicities above and
      below the threshold level required for efficient secretion. The flanking amino
      and carboxyl termini were designed to maintain the general features and relative
      hydrophobicity of their counterparts in the wild-type PhoA signal sequence. Using
      the phoA gene, the signal peptide region was modified to generate mutants
      corresponding to the model sequences. Transport studies in Escherichia coli
      confirmed that completely idealized signal sequences, which lack a helix-breaking
      proline or glycine residue, can be functional if the core region is sufficiently
      hydrophobic and that one positively charged residue in the amino terminus is
      adequate for efficient transport. The corresponding peptides were chemically
      synthesized and exhibited HPLC retention times that reflect the relative
      hydrophobicities of the sequences. Structural analyses of the isolated peptides
      by circular dichroism demonstrate solvent dependence and exceptionally stable
      alpha-helix formation by the functional signal peptides in trifluoroethanol.
      Although leucine and alanine residues are often predicted to have similar
      propensities for forming an alpha-helix, considerably higher alpha-helical
      content is observed in the signal peptides which contain predominantly
      polyleucine core regions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7632689
TI  - Comparison of the enzymatic properties of the Na,K-ATPase alpha 3 beta 1 and
      alpha 3 beta 2 isozymes.
AB  - The coexpression of multiple isoforms of the alpha and beta subunits of the Na,K
      ATPase in mammalian tissues gives rise to the complex molecular heterogeneity
      that characterizes the Na pump. The expression of the different Na,K-ATPase
      isoforms in insect cells using recombinant baculoviruses represents a useful
      system for the analysis of Na,K-ATPase isoform function. In the present study, we
      use this system to direct the expression of the rat Na,K-ATPase alpha 3 beta 1
      and alpha 3 beta 2 in sf-9 cells, a cell line derived from the ovary of the fall
      armyworm, Spodoptera frugiperda. The association of alpha 3 with either beta 1 or
      beta 2 results in catalytically competent Na,K-ATPase isozymes. Analysis of the
      kinetic characteristics of these enzymes demonstrates that the accompanying beta
      subunit isoform does not drastically affect the properties of the alpha 3
      polypeptide. This is evidenced by the similar turnover numbers, apparent
      affinities for K+ and ATP, and the comparable high sensitivity to ouabain
      exhibited by both isozymes. The kinetic dependence on Na+, however, is different
      for both isozymes, with alpha 3 beta 2 displaying a 1.6-fold higher apparent
      affinity for the cation than alpha 3 beta 1. Comparison with other Na,K-ATPase
      isozymes shows that the apparent Na+ affinity of alpha 3 beta 2 is similar to
      that of the alpha 1 beta 1 Na pump widely expressed in every tissue;
      nevertheless, its reactivity toward K+, ATP, and ouabain are characteristic of
      the alpha 3 isoform. The most pronounced kinetic differences in Na,K-ATPase
      function are a result of variations in alpha isoform composition.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7632691
TI  - Kinetic stabilization of microtubule dynamics at steady state in vitro by
      substoichiometric concentrations of tubulin-colchicine complex.
AB  - We have analyzed the effects of tubulin-colchicine (TC)-complex on the dynamic
      instability behavior of bovine brain microtubules at steady state in vitro using
      video microscopy. Incorporation of low numbers of TC-complexes per microtubule
      strongly suppressed dynamics at the plus ends by reducing the rate and extent of
      growing and shortening and by increasing the time microtubules spent in an
      attenuated state, neither growing nor shortening detectably. In addition, TC
      complex strongly suppressed the catastrophe frequency and increased the rescue
      frequency. At low concentrations (0.02-0.05 microM), TC-complex suppressed
      dynamics without reducing the polymer mass or the mean microtubule length. Such
      strong suppression of microtubule dynamics by low TC-complex concentrations in
      the absence of polymer mass changes demonstrates that microtubule dynamics are
      more sensitive to the actions of TC-complex than the polymer mass. Significant
      reduction of polymer mass occurred at relatively high TC-complex concentration (>
      0.05 microM). However, the surviving microtubules were extremely stable. Thus, TC
      complex stabilizes microtubules even though the microtubules can transiently
      depolymerize when TC-complex is added. The data also directly establish that
      kinetic suppression of dynamics by colchicine at low concentrations is effected
      by a low number of TC-complexes at the microtubule ends.

PMID- 7632692
TI  - Pseudomonas mevalonii 3-hydroxy-3-methylglutaryl-CoA lyase: testing the function
      of the active site cysteine by site-directed mutagenesis.
AB  - Pseudomonas mevalonii 3-hydroxy-3-methylglutaryl-CoA lyase is affinity labeled by
      2-butynoyl-CoA; peptide sequence analysis demonstrates C237 to be the site of
      modification [Hruz et al. (1992) Biochemistry 31, 6842-6847]. In order to
      evaluate whether C237 functions in the chemistry of hydroxymethylglutaryl-CoA
      cleavage, cassette mutagenesis has been employed to alter wild-type DNA to encode
      serine or alanine at residue 237. ESR measurements indicate that the purified
      mutant enzymes bind stoichiometric amounts of the spin-labeled substrate analog,
      R.CoA, which has been established as a competitive inhibitor. Binding affinities
      measured with C237S (Kd = 92 microM) and C237A (Kd = 97 microM) lyases are
      comparable to that observed with wild-type lyase. The rotational dynamics of
      R.CoA bound to mutant enzymes are also very similar to those for R.CoA bound to
      wild-type lyase. These observations suggest that the mutant enzymes are
      structurally intact. In view of this demonstrated structural integrity, it is
      significant that the VmaxS of C237A and C237S are approximately 4 x 10(4)- and
      approximately 725-fold lower, respectively, than the value measured for wild-type
      hydroxymethylglutaryl-CoA lyase. The C237S enzyme exhibits a Km = 53 microM for
      substrate; this value is only 2-fold higher than the Km of the wild-type enzyme.
      Additionally, we report that the residual activity in C237S hydroxymethylglutaryl
      CoA lyase is unaffected by 2-butynoyl-CoA under conditions which support
      inactivation of wild-type enzyme. These results are consistent with an active
      site assignment to C237, confirming the prediction based on the affinity
      labeling/peptide mapping data.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7632693
TI  - Sequence preference for strand cleavage of gapped duplexes by dynemicin A:
      possible mechanism of sequence-dependent double-stranded breaks.
AB  - A double-stranded DNA cleavage mechanism by a novel enediyne type antitumor
      antibiotic, dynemicin A, has been investigated through sequence-dependent strand
      breakage of a series of duplexes containing a single nucleotide gap. We found
      that (1) dynemicin A breaks specifically at the 3'-shifted position by one base
      opposite the gap, (2) the strong cleavage is detected at 5'-Pu_Pu/3'-PyPuPy
      sequences, and (3) dynemicin H (aromatized form of dynemicin A) gives only a
      small inhibition effect (20%) on the cleavage of gapped duplex by dynemicin A.
      The long half-life of aromatization of dynemicin A (118 min, in the presence of
      DNA) obtained from HPLC analysis provides enough time for the second cleavage.
      The present results strongly indicate a two-step mechanism for the double
      stranded DNA scission of dynemicin A. Namely, this double-stranded break is
      caused by two drug molecules, each of which cuts one DNA strand.

PMID- 7632694
TI  - Structural and functional analysis of the human KB cell folate receptor gene P4
      promoter: cooperation of three clustered Sp1-binding sites with initiator region
      for basal promoter activity.
AB  - The human folate receptors (hFRs) are important in the cellular accumulation of
      folates and antifolates. We described the structure of the human KB cell FR (hFR
      KB) gene and identified two discrete promoter regions (P1 and P4) upstream from
      exons 1 and 4, respectively (Elwood et al., 1993). To further understand the
      molecular basis of hFR expression, we have now analyzed the basal transcription
      of the P4 promoter localized upstream of a major transcription start site. The
      sequence upstream from exon 4 contains several potential transcriptional factor
      binding sites and a consensus initiator region sequence at the transcription
      start site but does not contain canonical TATA or CAAT boxes. While deletion of a
      5' flanking sequence from nt -1023 to nt -605 of P4 promoter region decreases the
      luciferase reporter gene expression in KB cells to 54-70% of control construct,
      the removal of the sequence between nt -292 and nt -46 markedly decreases the
      activity to 3%. DNase I footprints and competitive mobility shift and supershift
      mobility assays indicate that Sp1 or Sp1-related nuclear protein(s) bind to three
      clustered GC-rich regions within the sequence between nt -292 and nt -46 of the
      hFR-KB P4 promoter. Both in vitro and in vivo analyses of the expression of
      promoter constructs containing site-specific mutation(s) of these three Sp1
      binding sites and initiator sequence demonstrate that each of three Sp1 sites and
      the initiator sequence are required for optimum promoter activity and that they
      interact cooperatively in this P4 promoter of the hFR-KB gene.

PMID- 7632695
TI  - Berenil [1,3-bis(4'-amidinophenyl)triazene] binding to DNA duplexes and to a RNA
      duplex: evidence for both intercalative and minor groove binding properties.
AB  - Berenil is an antitrypanosomal agent that binds to nucleic acid duplexes. The
      generally accepted mode of berenil binding is via complexation into the minor
      groove of AT-rich domains of DNA double helices. We find that berenil can bind to
      RNA as well as DNA duplexes, while exhibiting properties characteristic of both
      intercalation as well as minor groove binding. More specifically, we use
      spectroscopic, calorimetric, and hydrodynamic techniques to characterize berenil
      binding to four DNA duplexes and to one RNA duplex. Our results reveal the
      following features: (i) Berenil binding to the poly[d(A-T)]2, poly(dA).poly(dT),
      poly[d(I-C)]2, poly[d(G-C)]2, and poly(rA).poly(rU) duplexes exhibits
      intercalative as well as minor groove binding characteristics. (ii) The apparent
      "site sizes" associated with berenil binding to these five duplexes range from 1
      to 13 base pairs per bound berenil and depend, in part, on the host duplex. One
      of the site sizes common to all five duplexes is consistent with berenil binding
      to the minor groove. (iii) The apparent berenil binding affinity follows the
      hierarchy: poly(dA).poly(dT) > poly-[d(A-T)]2 approximately poly[d(I-C)]2 >>
      poly(rA).poly(rU) > poly[d(G-C)]2. (iv) Viscometric data reveal properties
      characteristic of a significant contribution from an intercalative mode of
      binding when berenil interacts with the poly[d(A-T)]2, poly[d(I-C)]2, poly[d(G
      C)]2, and poly(rA).poly(rU) duplexes, while revealing an apparent
      nonintercalative mode when the drug binds to the poly(dA).poly(dT) duplex. (v)
      Berenil binding unwinds negative supercoils in the pBR322 plasmid, an observation
      consistent with an intercalative mode of binding to duplex DNA. (vi) Salt
      dependent melting data suggest that both positively charged amidino groups of
      berenil participate in the complexation of the drug to the poly[d(I-C)]2,
      poly[d(A-T)]2, poly(dA).poly(dT), and poly(rA).poly(rU) duplexes, while also
      suggesting that the binding event is site-specific. In the aggregate, our results
      suggest that, in contrast to the conventional wisdom, berenil can exhibit
      intercalative as well as minor groove binding properties when it binds to both
      DNA and RNA duplexes, while also exhibiting a preference for DNA duplexes with
      unobstructed minor grooves. We comment on the potential correlation between
      drugs, such as berenil, that exhibit "mixed" binding motifs and those that
      express anticancer activity via inhibition of topoisomerase I activity.

PMID- 7632696
TI  - Thermodynamic and kinetic characterization of the binding of the TATA binding
      protein to the adenovirus E4 promoter.
AB  - A thermodynamic analysis of the binding of the TATA binding protein (TBP) from
      Saccharomyces cerevisiae to the adenovirus E4 promoter was conducted using
      quantitative DNase I "footprint" titration techniques. These studies were
      conducted to provide a foundation for studies of TBP structure-function relations
      and its assembly into transcription preinitiation complexes. The binding of TBP
      to the E4 promoter is well described by the Langmuir binding polynomial,
      suggesting that no linked equilibria contribute to the binding reaction under the
      conditions examined. Van't Hoff analysis yielded a nonlinear dependence on
      temperature with the TBP-E4 promoter interaction displaying maximal affinity at
      30 degrees C. An unusually negative value of the apparent standard heat capacity
      change, delta Cp degrees = -3.5 +/- 0.5 kcal/mol.K, was determined from these
      data. The dependence of the TBP-E4 promoter interaction on [KCl] indicates that
      3.6 +/- 0.3 K+ ions are displaced upon complex formation. Within experimental
      error, no linkage of proton binding with the TBP-E4 promoter interaction is
      detectable between pH 5.9 and 8.7. Rates of association of TBP for the E4
      promoter were obtained using a novel implementation of a quench-flow device and
      DNase I "footprinting" techniques. The value determined for the second-order rate
      constant at pH 7.4, 100 mM KCl, 5 mM MgCl2, 1 mM CaCl2, 30 degrees C (ka = 5.2 +/
      0.5) x 10(5) M-1 s-1) confirms the results obtained by Hawley and co-workers
      [Hoopes, B.C., LeBlanc, J.F., & Hawley, D.K. (1992) J. Biol. Chem. 267, 11539
      11547] and extends them through TBP concentrations of 636 nM.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7632697
TI  - Cytochrome c peroxidase-catalyzed oxidation of yeast iso-1 ferrocytochrome c by
      hydrogen peroxide. Ionic strength dependence of the steady-state parameters.
AB  - The cytochrome c peroxidase-catalyzed oxidation of yeast iso-1 ferrocytochrome c
      by hydrogen peroxide can be understood on the basis of a mechanism involving two
      cytochrome c-binding sites on cytochrome c peroxidase. Values of the equilibrium
      dissociation constants for both the high- and low-affinity binding sites
      determined from the steady-state kinetic measurements agree well with published
      values obtained by vastly different techniques, providing strong support for the
      two-binding site mechanism. Maximum enzyme turnover via oxidation of cytochrome c
      bound at the high-affinity site increases from 2 to 860 s-1 as the ionic strength
      is increased from 0.010 to 0.20 M. Oxidation of yeast iso-1 ferrocytochrome c is
      faster in the 2:1 complexes of cytochrome c peroxidase compounds I and II in
      comparison to the 1:1 complexes. The oxidation rates in the 2:1 complex are
      macroscopic rate constants equal to the sum of the oxidation rates via both the
      high- and low-affinity sites. The maximum enzyme turnover via the 2:1 complex
      increases from 1100 to 2700 s-1 over the ionic strength range 0.010-0.070 M.

PMID- 7632698
TI  - Oxidation of yeast iso-1 ferrocytochrome c by yeast cytochrome c peroxidase
      compounds I and II. Dependence upon ionic strength.
AB  - The reduction of cytochrome c peroxidase compound I by excess yeast iso-1
      ferrocytochrome c is biphasic. Two pseudo-first-order rate constants can be
      measured by stopped-flow techniques. The fastest rate process is the reduction of
      cytochrome c peroxidase compound I to compound II, and the slower process is the
      reduction of II to the native enzyme. The yeast iso-1 ferrocytochrome c
      concentration dependence of the reduction of cytochrome c peroxidase compound I
      to compound II is consistent with a mechanism involving two binding sites for
      cytochrome c on cytochrome c peroxidase. Electron transfer from cytochrome c
      bound at the high-affinity binding site to the Fe(IV) site in cytochrome c
      peroxidase compound I is dependent upon ionic strength, increasing from 15 +/- 6
      to 2000 +/- 100 s-1 over the ionic strength range 0.01-0.20 M. The reduction rate
      of the Fe(IV) site in the 2:1 yeast iso-1 ferrocytochrome c/cytochrome c
      peroxidase compound I complex is essentially independent of ionic strength with a
      value of 3800 +/- 300 s-1. The Fe(IV) site in cytochrome c peroxidase compound I
      is preferentially reduced by yeast ferrocytochrome c between 0.01 and 0.20 M
      ionic strength while the Trp-191 radical is preferentially reduced above 0.30 M
      ionic strength. The association rate constant for the binding of yeast iso-1
      ferrocytochrome c to cytochrome c peroxidase compound I can be evaluated and
      varies from a remarkable 1 x 10(10) M-1 s-1 at 0.01 M ionic strength to 1.2 x
      10(5) M-1 s-1 at 1.0 M ionic strength. Between 0.01 and 0.20 M ionic strength,
      the reduction of cytochrome c peroxidase compound II to the native enzyme is
      anomalous. The reaction is independent of the cytochrome c concentration and
      directly proportional to the initial cytochrome c peroxidase compound I
      concentration.

PMID- 7632700
TI  - Myths about leadership.

PMID- 7632699
TI  - In pursuit of leadership.

PMID- 7632701
TI  - Leadership development.

PMID- 7632702
TI  - Liposomal entrapment of the neutrophil-derived peptide indolicidin endows it with
      in vivo antifungal activity.
AB  - Indolicidin, a cationic tridecapeptide amide isolated from the granules of bovine
      neutrophils, has been found to possess potent antimicrobial activity in vitro but
      its nonselective toxicity could restrict its therapeutic utility. We found that
      the concentration at which indolicidin disrupts washed human red blood cell
      membranes coincided with the concentration at which indolicidin self associates.
      Because of a preponderance of hydrophobic residues, we believed that indolicidin
      would partition into liposomes which would restrict its exchange with biological
      tissues and consequently reduce its toxicity. Fluorescence spectroscopy of
      indolicidin added to 100 nm liposomes comprised of POPC, POPC/cholesterol (60:40
      mol%), DPPC, or DPPC/cholesterol (60:40) revealed a large blue-shift and an
      increase in intensity of the emission profile indicating insertion into the
      bilayer. Of the lipids tested, POPC exhibited the highest degree of indolicidin
      binding as determined by fluorescence and encapsulation efficiency. By
      sequestering indolicidin within the lipid bilayer of 100 nm POPC liposomes we
      significantly reduced its toxicity to CHO/K1 cells. Likewise, the systemic
      toxicity of liposomal indolicidin in Balb/c mice was decreased dramatically
      relative to aqueous solutions; the maximum dose at which no deaths occurred was
      0.4 mg/kg for free indolicidin versus 40 mg/kg for indolicidin-POPC. Because of
      this decrease in toxicity, we were able to administer liposomally encapsulated
      material at significantly higher concentrations than unencapsulated aqueous
      material and achieve efficacy in treating animals systemically infected with
      Aspergillus fumigatus. Liposomal but not free indolicidin was found to be
      effective in obtaining cures. This report is the first description of the in vivo
      therapeutic activity of a neutrophil-derived antimicrobial peptide and suggests
      that liposomal treatment modalities will provide effective strategies for
      endowing this class of compounds with pharmacological utility.

PMID- 7632703
TI  - An anion channel from transverse tubular membranes incorporated into planar
      bilayers.
AB  - Transverse tubular (TT) vesicles from rabbit skeletal muscle were incorporated
      into planar lipid bilayers to characterize the chloride channel. The single
      channel conductance of the channel was 40 pS in choline-Cl solution (cis, 300
      mM/100 mM, trans). The gating rate of the channel does not depend on membrane
      voltage. The channel was blocked by stilbene derivatives (DIDS and SITS), which
      are known as inhibitors of voltage-dependent Cl- channels of the Torpedo electric
      organ, from both sides of the membrane. An inhibitor of voltage-dependent Cl-
      channels of skeletal muscles, 9-anthracene carboxylic acid (9-AC) inhibited the
      channel from the cis side of the membranes, which corresponded to the cytoplasmic
      space. Ethacrynic acid (EA), which is reported to inhibit Cl- conductance of the
      kidney and trachea, decreased the open probability of the TT Cl- channel
      concentration dependently. Indanyloxyacetic acid (IAA), which is also reported to
      be an inhibitor of kidney and trachea Cl- channels, decreased the single channel
      current without affecting open probability of the TT Cl- channel.

PMID- 7632704
TI  - Membrane potential-driven translocation of a lipid-conjugated rhodamine.
AB  - The present study demonstrates that the permanently positively charged, lipid
      conjugated rhodamine, R18, can be transported from the outer to the inner leaflet
      of lipid bilayers in response of a transmembrane potential (negative inside).
      This conclusion was based on the following observations. (i) A fast decrease of
      the R18 fluorescence, when present at self-quenching concentrations in DOPC large
      unilamellar vesicles, was revealed upon induction of a valinomycin-induced K(+)
      diffusion potential. (ii) Iodide quenching experiments demonstrated that R18 was
      no longer accessible to externally added aqueous quencher after application of a
      transmembrane potential. (iii) 2H-NMR measurements, using DOPC, specifically
      deuterated at the alpha-position of the phosphocholine head group, revealed a
      massive transbilayer movement of R18 upon induction of a membrane potential. The
      extent of the fluorescence changes were found to be dependent on the magnitude of
      the applied transmembrane potential, which opens possibilities for novel
      applications of R18 as an internal lipid-conjugated membrane potential probe.

PMID- 7632705
TI  - Effect of sterol structure on molecular interactions and lateral domain formation
      in monolayers containing dipalmitoyl phosphatidylcholine.
AB  - Molecular associations between different sterols and dipalmitoyl
      phosphatidylcholine (DPPC) were examined in monolayers at the air/water
      interface. The sterols examined included cholesterol, 5-cholesten-3- one, 4
      cholesten-3 beta-ol, 4-cholesten-3-one, cholesteryl acetate, and cholesteryl
      methyl-and ethyl ether. Information about the long-range order in pure sterol
      monolayers, as well as lateral domain-formation in mixed sterol/DPPC monolayers
      was obtained from the lateral miscibility or distribution of NBD-cholesterol
      (present at 0.5 mol%), as determined by monolayer epifluorescence microscopy. It
      was observed that the miscibility of NBD-cholesterol with the host sterol was
      limited in all monolayers except those of 5-cholesten-3-one and 4-cholesten-3
      one, suggesting that only these monolayers lacked a long-range order present in
      the other sterol monolayers. Note that the term long-range order does not
      necessarily imply that the monolayer is solid. In mixed monolayers containing 3
      beta-OH sterols and DPPC, cholesterol formed laterally condensed domains whereas
      4-cholesten-3 beta-ol did not. This finding suggest that the sterols/DPPC
      interaction is sensitive to the position of the double-bond of the sterol
      molecule (delta 5 versus delta 4). Neither of the 3-keto sterols formed laterally
      condensed domains with DPPC. Cholesteryl acetate, however, formed lateral domains
      with DPPC which were in part similar to those seen in the cholesterol/DPPC
      system. The domains formed were circular, indicating their fluid nature. Mixed
      monolayers containing either of the ether sterol derivatives failed to produce
      clearly defined condensed domains with DPPC, although both mixed monolayers had a
      surface texture which suggested some degree of nonuniform distribution of the
      fluorescent probe. In summary, these novel results directly demonstrate the
      selective importance of both the delta 5 double bond, as well as of specific
      functional groups at the 3-position, for the molecular association with DPPC, and
      consequently for the formation of sterol/phospholipid-rich lateral domains.

PMID- 7632706
TI  - Phase behaviour of distearoylphosphatidylethanolamine in glycerol--a thermal and
      X-ray diffraction study.
AB  - The phase behaviour of 1,2-distearoylphosphatidylethanolamine in glycerol has
      been examined using differential scanning calorimetry and real-time synchrotron X
      ray diffraction methods. Dry phospholipid and phospholipid dispersed in glycerol
      over the concentration range 2.4%-90% (w/w) was equilibrated for 30 min at 20
      degrees C and thermal and structural parameters on the temperature range 60
      degrees C to 110 degrees C recorded during an initial heating and subsequent
      reheating. The characteristic feature of the initial heating scan was a direct
      lamellar crystalline to inverted hexagonal phase transition. In the subsequent
      cooling scan a lamellar gel structure was formed from the non-lamellar phase
      which transformed, on reheating, to a lamellar crystalline phase in which the
      acyl chain packing was titled with respect to the bilayer plane. The mechanism of
      the formation of the two crystalline phases was examined in the context of a
      relaxation model, where the liquid-crystal phase below the transition temperature
      from lamellar crystalline phase is metastable. A binary phase diagram over the
      temperature range 60 degrees C to 110 degrees C has been constructed.

PMID- 7632707
TI  - Alterations in the properties and isoform ratios of brain Na+/K(+)-ATPase in
      streptozotocin diabetic rats.
AB  - In this study we analysed the changes in the properties of rat cerebral cortex
      Na+K(+)-ATPase in streptozotocin induced diabetes (STZ-diabetes). Special attempt
      was made to determine whether insulin treatment of diabetic animals could restore
      the altered parameters of this enzyme. Na+/K(+)-ATPase activity was found to be
      decreased by 15% after 2 weeks, and by 37% after 4 weeks in diabetic rat brains
      with a parallel decrease in maximal capacity of low affinity ouabain binding
      sites. There was no significant change in the high affinity ouabain binding
      sites. The Kd values did not change significantly. Western blot analysis of brain
      Na+/K(+)-ATPase isoforms indicated a 61 +/- 5.8% and 20 +/- 2.8% decrease of the
      alpha 1 and alpha 3 isoforms, respectively in 4 weeks diabetic animals. Change in
      the amount of the alpha 2 isoform proved to be less characteristic. Both types of
      beta subunit isoform showed a significant decrease in four weeks diabetic rats.
      Our data indicate a good correlation in diabetic rats between changes in Na-/K(+)
      ATPase activity, low affinity ouabain binding capacity and the level of alpha 1
      isoform. While insulin treatment of diabetic animals restored the blood glucose
      level to normal, a complete reversal of diabetes induced changes in Na+/K(+)
      ATPase activity, ouabain binding capacity and Na+/K(+)-ATPase isoform composition
      could not be achieved.

PMID- 7632708
TI  - Cross-linking of the ryanodine receptor/Ca2+ release channel from skeletal
      muscle.
AB  - The relationship between the tetrameric organization of the ryanodine receptor
      (RyR) and its activity in binding of ryanodine was approached through cross
      linking studies using several bifunctional reagents, differing in their linear
      dimensions and flexibility, as well as in the reactivity of the active groups.
      Cross-linking with: 1,5-difluoro-2,4-dinitrobenzene (DFDNB); di(fluoro-3
      nitrophenyl)sulfone (DFNPS), 1-ethyl-3-(3-dimethylamino)propyl)carbodiimide
      (EDC); dimethyl suberimidate (DMS); ethylene glycol bis(succinimidylsuccinate)
      (EGS); and glutaraldehyde resulted in the disappearance of the, 470 kDa, RyR
      monomer protein band with concomitant appearance of additional bands of molecular
      masses higher than the monomer. At the relatively low concentrations of the
      reagents and the conditions used, RyR is the only cross-linked protein of SR
      membranes. The 'new' protein bands cross-react with antibodies against the RyR
      and correspond to dimers and tetramers of the RyR subunits while trimers were not
      detectable. DFDNB and DFNPS produced also a 560 kDa protein band which probably
      represents an intramolecular cross-linked monomer. The SDS-electrophoretic
      patterns of the cross-linked purified RyR resemble those of the membrane-bound
      receptor. Ryanodine binding to the high-affinity site was inhibited by
      modification of SR membranes with DFDNB and DFNPS, but not with DMS, EDC, EGS and
      glutaraldehyde, although RyR was completely cross-linked. The inhibition by DFDNB
      and DFNPS is due to modification of a specific lysyl residue which is also
      involved in the control of Ca2+ release. On the other hand, cross linking of the
      RyR with glutaraldehyde or EGS resulted in inhibition of ryanodine binding to the
      low-affinity, but not to the high-affinity binding sites. Thus, the cross-linking
      of two or more sites in each monomer (which lead to fixation of dimers or
      tetramers) did not prevent the conformational changes involved in the binding and
      occlusion of ryanodine at the high-affinity site, but inhibited its binding to
      the low-affinity sites.

PMID- 7632709
TI  - Insertion of an uncharged polypeptide into the mitochondrial inner membrane does
      not require a trans-bilayer electrochemical potential: effects of positive
      charges.
AB  - Mitochondria with a ruptured outer membrane exhibited impaired import into this
      membrane of an outer membrane fusion protein containing the signal-anchor
      sequence of Mas70p. However, the Mas70p signal-anchor efficiently targeted and
      inserted the protein directly into exposed regions of the inner membrane. Import
      into the inner membrane was dependent on delta psi and this dependence was due to
      the presence of the positively-charged amino acids located at positions 2, 7, and
      9 of the signal-anchor. In contrast to wild-type signal-anchor, mutants lacking
      the positively-charged residues mediated import into the inner membrane in both
      the presence and absence of delta psi. The results suggest two conclusions: (1)
      delta psi-dependent import of the signal-anchor sequence was due exclusively to
      an effect of delta psi on the positively-charged domain of the signal-anchor,
      rather than to an effect of delta psi on a property of the inner membrane import
      machinery; (2) in the absence of delta psi, the positively-charged domain of the
      signal-anchor prevented the otherwise import-competent signal-anchor from
      inserting into the membrane. This suggests that the positively-charged domain
      leads import across the inner membrane, and that delta psi is required to
      vectorially clear this domain in order to allow the distal region of the signal
      anchor to enter the translocation pathway. The implications of these findings on
      the mechanism of import into the mitochondrial inner membrane and matrix are
      discussed.

PMID- 7632710
TI  - Increased permeability of phase-separated liposomal membranes with mixtures of
      ethanol-induced interdigitated and non-interdigitated structures.
AB  - It has been suggested by many workers using model membranes that the
      interdigitated structure formation, in which the acyl chains fully interpenetrate
      the hydrocarbon chains of the opposing monolayer, plays an important role in
      regulating many functions of biomembranes. In the present study the control of
      permeability was focused on as one of the biomembrane functions, and the effects
      of ethanol on the permeability of large unilamellar vesicles made by the
      extrusion technique (LUVET) (average diameter: about 250 nm), composed of
      dipalmitoyl or egg yolk phosphatidylcholines, were studied by monitoring the
      leakage of fluorescent dye, calcein, entrapped in the inner aqueous phase of the
      LUVET. The permeability was estimated from the apparent rate constant of calcein
      leakage at 25 degrees C. Large permeabilities were observed in the region of 0.6
      M to 1.3 M ethanol, with a concentration dependence. In this range of ethanol
      concentrations the normal bilayer and interdigitated structure coexist and the
      membrane is in a phase-separated state. The large permeability is due to the
      instability of the boundary regions, the interdigitated membrane being
      characterized by a thinner structure and more rigid hydrocarbon regions in the
      layer than its non-interdigitated counter part. These results suggest the
      possibility of biomembrane-permeability regulation by interdigitated membrane
      formation.

PMID- 7632711
TI  - Interaction of phosphatidylcholine liposomes with the human stratum corneum.
AB  - The interaction of dimyristoylphosphatidylcholine liposomes with the human
      stratum corneum was investigated by confocal laser scanning microscopy and
      differential scanning calorimetry. Human skin is characterized by a high
      autofluorescence. By introducing appropriate optical filters the autofluorescence
      of the skin was depressed and the penetration profile of fluorescence labelled
      vesicles was investigated. From optical sectioning it was obvious that neither
      the vesicles nor the fluorophore N-(lissamine rhodamine B
      sulfonyl)diacylphophatidylethanolamine (Rho-PE) penetrates in detectable amounts
      into the human skin. Differential scanning calorimetry of human stratum corneum
      revealed, that the peak positions of the human stratum corneum specific
      endothermic transitions at 10 degrees C, 35 degrees C, 50 degrees C, 62 degrees
      C, 73 degrees C and 81 degrees C did not change significantly after 18 h of non
      occlusive vesicle application. However, the enthalpy of the transitions at 35
      degrees C, 50 degrees C, 62 degrees C and 73 degrees C, estimated through peak
      heights increased, relative to the protein related peak at 81 degrees C. A novel
      transition at 10 degrees C was observed. From these data we conclude that DMPC
      liposomes do not penetrate intact into the human skin. We deduce, however, that
      the vesicles disintegrate at the surface of stratum corneum after non-occlusive
      application. The individual lipid molecules then interact with the lipid barrier
      of the stratum corneum and penetrate into the latter, which results in an
      increase of the enthalpy, related to the lipid components of the SC.

PMID- 7632712
TI  - Small angle X-ray diffraction and differential scanning calorimetric studies on O
      methyl-(-)-delta 8-tetrahydrocannabinol and its 5' iodinated derivative in
      membrane bilayers.
AB  - We have previously studied and compared the location of (-)-delta 8
      tetrahydrocannabinol (delta 8-THC) with that of O-methyl-delta 8-THC (Me delta 8
      THC) in the membrane using partially hydrated dimyristoylphosphatidylcholine
      (DMPC) bilayers ((Mavromoustakos et al. (1990) Biophys. Acta 1024, 336-344; Yang
      et al. (1993) Life Sci. 53, 117-122). delta 8-THC was found to be located near
      the membrane interface with its phenolic hydroxyl group anchored near the
      carbonyl groups of DMPC while the more lipophilic Me-delta 8-THC is located
      deeper in the membrane bilayer. Parallel experiments using Me-delta 8-THC and its
      5'-iodo analog (5'-I-Me-delta 8-THC) allowed us to determine the topography of
      these two molecules in the bilayer. Our results from small angle X-ray
      diffraction and differential scanning calorimetry (DSC) combined with previous
      data on the orientation of Me-delta 8-THC in model membranes, led us to the
      conclusion that these molecules intercalate between contiguous acyl chains in the
      lipophilic moiety of the membrane bilayer. The terminal iodo group in 5'-I-Me
      delta 8-THC was found to reside in a region extending approx. +/- 5 A from the
      center of the bilayers. The location of Me-delta 8-THC in the membranes as well
      as its orientation may explain its inability to effectively perturb the bilayer
      lipid chains.

PMID- 7632713
TI  - A Synechococcus gene encoding a putative pore-forming intrinsic membrane protein.
AB  - A cyanobacterium, Synechococcus species PCC7942, has a gene encoding a copper
      transporting P-type ATPase, which is located in the thylakoid membrane. At the 5'
      upstream of this ATPase gene, we identified another gene, which was supposed to
      be implicated in a copper-transport process. This novel gene was found to encode
      a putative pore-forming membrane protein that belongs to a growing family of
      homologous intrinsic membrane proteins (the MIP family of proteins), which
      include the major intrinsic protein (MIP) from animal lens fibre junction
      membranes, the tonoplast intrinsic protein (TIP) from vacuolar membranes of
      higher plants, and the Escherichia coli glycerol facilitator (GlpF) in the
      cytoplasmic membrane. The deduced product, named SmpX (Synechococcus membrane
      protein), is highly homologous throughout its entire sequence to these intrinsic
      membrane proteins which were postulated to be pore-forming proteins involved in a
      variety of transport processes. The primary amino acid sequence of SmpX shares
      all properties characteristic for members of the MIP family. SmpX is more similar
      to the eukaryotic members (e.g., nodulin-26 from soybean) than to the prokaryotic
      ones.

PMID- 7632714
TI  - A new strategy for attachment of antibodies to sterically stabilized liposomes
      resulting in efficient targeting to cancer cells.
AB  - The development of long-circulating formulations of liposomes (S-liposomes),
      sterically stabilized with lipid derivatives of poly(ethylene glycol) (PEG), has
      increased the likelihood that these liposomes, coupled to targeting ligands such
      as antibodies, could be used as drug carriers to deliver therapeutic drugs to
      specific target cell populations in vivo. We have developed a new methodology for
      attaching monoclonal antibodies to the terminus of PEG on S-liposomes. A new end
      group functionalized PEG-lipid derivative pyridylthiopropionoylamino-PEG-
      distearoylphosphatidylethanolamine (PDP-PEG-DSPE) was synthesized for this
      purpose. Incorporation of PDP-PEG-DSPE into S-liposomes followed by mild
      thiolysis of the PDP groups resulted in formation of reactive thiol groups at the
      periphery of the lipid vesicles. Efficient attachment of maleimide-derivatized
      antibodies took place under mild conditions even when the content of the
      functionalized PEG-lipid in S-liposomes was below 1% of total lipid. The
      resulting S-immunoliposomes showed efficient drug remote loading, slow drug
      release rates and increased survival times in circulation compared to liposomes
      lacking PEG. When antibodies recognizing several different tumor-associated
      antigens were coupled to the PEG terminus of S-liposomes a significant increase
      in the in vitro binding of liposomes to the target cells was observed. The
      binding of S-immunoliposomes containing entrapped doxorubicin to their target
      cell population resulted in increased cytotoxicity compared to liposomes lacking
      the targeting antibody.

PMID- 7632715
TI  - Entrapment of enzymes using organo-functionalized polysiloxane copolymers.
AB  - The present study expands previous work [(1984) Biochim. Biophys. Acta. 797, 343
      347] by showing that organo-functionalized polysiloxane copolymers could entrap
      two of the most frequently immobilized enzymes, i.e. urease and invertase with
      retention of biological activity. Urease was solidly entrapped in the polymer
      formed from a 1:3 mixture of 3-aminopropyltriethoxysilane and
      tetraethylorthosilicate. The entrapment yield and the activity of the entrapped
      enzyme are significantly greater than with other techniques reported to date.
      Significantly, the entrapped enzyme possessed greater activity than its solution
      counterpart (36% at higher amounts of enzyme entrapped). The entrapment process
      also rendered the enzyme more stable toward pH and temperature, and less
      susceptible toward the action of urea at high concentrations. In addition, the
      entrapment process significantly increased the stability, both operational and
      storage, of the urease enzyme. When invertase was entrapped in the same
      copolymer, it retained two thirds of its solution activity, but the entrapment
      yield was lower than that of urease. Results obtained during this study also
      suggested that the protein may be influencing polymer development in these
      systems and that the resultant polymer in turn may be affecting the enzyme's
      activity (see following paper for further discussion).

PMID- 7632717
TI  - Characterisation of a purified phospholipase A2 from the venom of the Papuan
      black snake (Pseudechis papuanus).
AB  - A neutral phospholipase A2 (PLA2) was separated from Pseudechis papuanus venom by
      a two-stage FPLC procedure of cation exhange and phenyl-Superose chromatography.
      It had a molecular mass of 15 kDa and a lower LD50 value than a co-separated
      haemorrhagic fraction, indicating a higher lethal potency. In vitro tests
      confirmed the powerful inhibition of platelet aggregation by the PLA2 and strong
      anticoagulant activity initially observed with whole venom. Ultrastructural
      studies showed that platelets lost their discoid shape and developed membranous
      projections with a general decrease in electron-density of the cytosol and
      disruption of the microfilaments following incubation with the enzyme. Amino acid
      sequence analysis of the N-terminus and some internal peptides demonstrated a
      high degree of homology with PLA2s from other Pseudechis venoms. Our results
      indicate that this fraction is the main agent responsible for the haemostatic
      disorders in envenomed patients.

PMID- 7632716
TI  - Influence of protein on polysiloxane polymer formation: evidence for induction of
      complementary protein-polymer interactions.
AB  - Results presented in the companion paper suggested that the protein itself might
      be actively involved in the polymerization process while being entrapped in
      polysiloxane polymers. It was speculated that the organo-functional side chains
      on the silanol monomers (or small oligomers) tended to associate with
      complementary residues on the protein surface during the polymerization process.
      This phenomenon might lead to complementary binding pockets for the protein on
      the polymer. To investigate this possibility, polysiloxane polymers were prepared
      from 3-aminopropyltriethoxysilane and tetraethylorthosilicate (1:3) in the
      presence of two proteins: urease and BSA. The entrapped proteins were removed by
      pronase digestion and washing and the resulting polymers evaluated for their
      ability to again bind the two proteins. It was found that urease preferentially
      bound to the polymer made in the presence of urease, and BSA preferentially bound
      to the polymer made in the presence of BSA. The absolute preferential binding
      excess was greater (30%) for urease binding relative to that observed for BSA
      (3%). However, in both cases the same relative binding ratio of 1.5 or 50% excess
      was found. A similar study using the closely related hemoglobin and myoglobin
      proteins failed to show comparable excess binding in the presence of the
      predetermined protein. In the latter case, it was demonstrated that the rebound
      proteins did not equilibrate with labeled solution proteins, indicating a very
      tight association with the polymer surface possibly masking any specificity which
      existed. However, it was possible to show that urea release of rebound hemoglobin
      from the polymer made in the presence of hemoglobin was less than for myoglobin
      bound to the same polymer and visa versa, again suggesting induced properties
      unique to the polymer prepared with the predetermined protein. To the extent that
      this notion of induced complementary order is correct, it may have implications
      in the development of protein specific adsorbants and in our understanding of
      polymer surface adhesion and the molding of template fine structure.

PMID- 7632718
TI  - Purification and characterization of alpha-D-mannosidase from Aspergillus sp.
AB  - alpha-D-Mannosidase from Aspergillus sp. was purified to homogeneity by
      preparative polyacrylamide gel electrophoresis (PAGE). The native enzyme of
      molecular mass 412 kDa (gel filtration) is made up of six identical subunits of
      molecular mass 69.2 kDa (SDS-PAGE) The enzyme is acidic (pI 4.5) and a
      glycoprotein with a carbohydrate content of 3.8%. The pH and temperature optima
      of the enzyme were in the range 6.0-6.5 and 50-55 degrees C, respectively. At pH
      6.0 the enzyme was stable for 30 min at 50 degrees C. The Km and Vmax for p
      nitrophenyl-alpha-D-mannopyranoside were 83 microM and 0.2 mumol/min per mg of
      the enzyme, respectively. The enzyme was strongly inhibited by 1 mM Hg2+ and Cu2+
      and partially by 30 mM glucose and mannose. The enzyme hydrolysed Man-alpha-(1
      3)Man at a very high rate followed by Man-alpha-(1-2)Man, while the rate of
      hydrolysis was low for Man-alpha-(1-6)Man. The rate of hydrolysis for high
      mannose oligosaccharide Man-6 was higher than for Man-9 and yeast mannan was not
      hydrolysed at all.

PMID- 7632719
TI  - A catalytic triad is required by the non-heme haloperoxidases to perform
      halogenation.
AB  - The bacterial non-heme haloperoxidases are highly related to an esterase from
      Pseudomonas fluorescens, at structural and functional levels. Both types of
      enzymes displayed brominating activity and esterase activity. The presence of the
      serine-hydrolase motif Gly-X-Ser-X-Gly, in the esterase as well as in all aligned
      haloperoxidase sequences, strongly suggested that they belong to the serine
      hydrolase family. Sequence alignment with several serine-hydrolases and secondary
      structure superimposition revealed the striking conservation of structural
      features characterising the alpha/beta-hydrolase fold structure in all
      haloperoxidases. These structural predictions allowed us to identify a potential
      catalytic triad in haloperoxidases, perfectly matching the triad of all aligned
      serine-hydrolases. The structurally equivalent triad in the chloroperoxidase CPO
      P comprised the amino acids Serine 97, Aspartic acid 229 and Histidine 258. The
      involvement of this catalytic triad in halogenation was further assessed by
      inhibition studies and site-directed mutagenesis. Inactivation of CPO-P by PMSF
      and DEPC strongly suggested that the serine residue from the serine-hydrolase
      motif and an histidine residue are essential for halogenation, similar to that
      demonstrated for typical serine-hydrolases. By site-directed mutagenesis of CPO
      P, Ser-97 was exchanged against alanine or cysteine, Asp-229 against alanine and
      His-258 against glutamine. Western blot analysis indicated that each mutant gene
      was efficiently expressed. Whereas the mutant S97C conserved a very low residual
      activity, each other mutant S97A, D229A or H258Q was totally inactive. This study
      gives the direct demonstration of the requirement of a catalytic triad in the
      halogenation mechanism.

PMID- 7632720
TI  - Different affinity of the two forms of human cytosolic thymidine kinase towards
      pyrimidine analogs.
AB  - Recent results showed that ATP enables a kinetically slow shift from a low
      affinity form to a high affinity form of human cytosolic thymidine kinase (TK1),
      as reflected by the respective apparent Km values for thymidine of 15 microM and
      0.7 microM. The shift is dependent on the concentration of enzyme protein, and
      calculations indicate that the low affinity form is predominant in G1 cells, and
      the high affinity form is predominant in S-phase cells. Here, we report that the
      two forms of TK1 differ manyfold in affinity to the substrate ATP, to the
      inhibitor dTTP and to various analogs of thymidine substituted in the pyrimidine
      or sugar. Furthermore, the kinetic reaction mechanisms suggest that the
      nucleoside analog. 3'-azidothymidine, used for treatment of infections with human
      immune deficiency virus (HIV), is not a substrate for the low affinity form of
      TK1.

PMID- 7632721
TI  - CD and NMR determination of the solution structure of a peptide corresponding to
      T4 lysozyme residues 38-51.
AB  - Solid phase methods have been used to synthesise a peptide corresponding to
      residues 38-51 of T4 lysozyme. The peptide, LYS(38-51), encompasses helix B in
      the crystal structure of T4 lysozyme. CD and 1H-NMR analysis showed that the
      peptide was unstructured in aqueous solution but adopted a helical conformation
      in the more hydrophobic environment provided by 50% TFE and SDS micelles. The
      solution structure derived from the NMR data was similar to that of the helix in
      the X-ray structure, although there was some fraying at the N-terminus.

PMID- 7632722
TI  - Development of surrogate substrates for neuropathy target esterase.
AB  - Seventeen substrates were synthesized and their activities as surrogate
      substrates for Neuropathy Target Esterase were tested. Substrates investigated
      are carbon analogs of phenylvalerate (1) with oxygen and sulfur substituted at
      the alpha, beta and gamma positions. Phenol and thiophenol esters of these
      analogs constitute two series of compounds tested. The ratio of catalytic
      hydrolysis to background hydrolysis increased at lower pH values with all
      substrates tested including phenylvalerate (1). There was more than a 2.5-fold
      increase in specific activity with phenylthiopropylethanoate (6) at pH of 6.75
      compared to phenylvalerate (1). Furthermore, a 19-fold decrease in Km is reported
      with compound 6. This and related compounds can be used as the basis of more
      sensitive assays for neuropathy target esterase. Thiophenyl esters in this series
      are sufficiently good substrates to hold promise in continuous assays.

PMID- 7632723
TI  - A complex of microperoxidase with a synthetic peptide: structural and functional
      characterization.
AB  - This paper reports the kinetic and thermodynamic characterization of the complex
      obtained by binding to microperoxidase (the heme-containing undecapeptide derived
      from peptic hydrolysis of cytochrome c) a 13 residues synthetic peptide with some
      propensity to acquire alpha-helical secondary structure (P13). Our results
      indicate that P13 binds to the sixth coordination position of the Fe(III) of
      microperoxidase (Keq = 4.8 x 10(4) M-1 at pH 7.0 and 25 degrees C) via the
      imidazole of His-12, forming a stable complex. The kinetics of complex formation,
      its secondary structure and its electrochemical activity are reported. This is a
      first step towards engineering a miniature-heme complex, for a better
      understanding of the mechanisms governing electron transfer in hemes and heme
      proteins, and possibly for novel biotechnological applications.

PMID- 7632724
TI  - Comparative studies of the conformation of the N-terminal fragments of
      staphylococcal nuclease R in solution.
AB  - In order to elucidate the folding of nascent peptide, five peptide fragments of
      staphylococcal nuclease R starting from N-terminal end and of different chain
      lengths are made by deletion of 47, 39, 28, 14 and 8 amino-acid residues from its
      C-terminal end, respectively. Changes in conformation of the N-terminal fragments
      have been compared by using Fourier-transform infrared spectra, far-ultraviolet
      circular dichroism spectra and analysis of surface hydrophobicity. The
      experiments indicate that all the five fragments have certain amounts of residual
      structure; in general, with increasing the peptide chain, the contents of
      secondary structure and the enzyme's activity of the peptide increase, and the
      exposed hydrophobic side chains brought about by the deletion of C-terminal
      residues are gradually buried in the interior of the nuclease. However, the
      ordered secondary structures do not always increase with increasing the peptide
      chain. Further growth of the length of the peptide chain could have an important
      effect on the conformation of the peptide fragment already synthesized,
      suggesting some structural adjustments should be necessary in order for the newly
      synthesized polypeptide to attain its final native conformation. These results
      support Tsou's nascent peptide folding hypothesis (Tsou, C.-L. (1988)
      Biochemistry 27, 1809-1812).

PMID- 7632725
TI  - Identification of two specific lysines responsible for the inhibition of
      phospholipase A2 by manoalide.
AB  - Manoalide, a natural product of sponge, irreversibly inhibits phospholipase A2
      (PLA2) by reacting with lysine residues. Cobra venom PLA2 mutants were
      constructed in which four of the six lysine residues were independently replaced
      by arginine or methionine, which cannot react with manoalide. The mutants were
      overexpressed in Escherichia coli, renatured, and purified. The enzyme mutants
      lacking Lys-6 (K6R and K6M) or Lys-79 (K79R) were inhibited only 40% by manoalide
      while the native cobra venom PLA2 was inhibited 80% under the same conditions.
      This means that the manoalide modification of either Lys-6 or Lys-79 accounted
      for only half of the manoalide inhibition. The double mutant (K6R79R) was not
      inhibited by manoalide at all. Lys-56 (K56R) and Lys-65 (K65R) mutants were
      inhibited to the same extent as the native enzyme which indicates that these
      residues are not responsible for any of the inhibitory effects produced by
      manoalide. These results demonstrate that the reaction of manoalide with both Lys
      6 and Lys-79 can account for all of its inhibition of cobra venom PLA2. The
      inhibition of PLA2 and its mutants with manoalide did not affect the activity of
      the enzyme toward monomeric substrate, which suggests that manoalide does not
      modify the catalytic site residues, that it does not block access to this site,
      and that its inhibition requires an interface. Furthermore, as with native PLA2,
      the activation of phosphatidylethanolamine hydrolysis by phosphorylcholine
      containing compounds was exhibited by all of the mutants suggesting that none of
      the lysines examined are essential for this activation.

PMID- 7632726
TI  - Cloning of the human 1 alpha,25-dihydroxyvitamin D-3 24-hydroxylase gene promoter
      and identification of two vitamin D-responsive elements.
AB  - A genomic DNA clone for 1 alpha,25-dihydroxyvitamin D-3 (1,25-(OH)2D3) 24
      hydroxylase was isolated from a human chromosome 20 library. It spans 2.42 kb,
      containing the first two exons, the first and part of the second introns, and a
      1.26 kb 5'-flanking region. Putative transcription cis-elements were revealed
      throughout the 5'-flanking region, including TATA box, CAAT box, GC boxes,
      vitamin D-responsive elements (VDRE), AP1, and AP2 sites. In a CAT reporter gene
      expression assay, the 24-hydroxylase promoter with its 1.2 kb 5'-flanking
      sequence elicits a 1,25-(OH)2D3-induced transactivation activity. Gel mobility
      shift assays of those putative DREs have identified that two different elements
      can form specific complexes with porcine intestinal nuclear extract (PINE). The
      specificity of VDRE-PINE complexes was verified by supershift assay with VDR
      specific monoclonal antibody VXIE10B6. The proximal element VDREp (-172/-143)
      consists of three direct repeat half-sites, GAGTCAgcgAGGTGAgcgAGGGCG, in anti
      sense orientation. The distal element VDREd (-293/-273) consists of two direct
      repeat half-sites, GCGTTCaccGGGTGT, also in anti-sense orientation. Both VDREs
      can direct a reporter gene expression using a heterologous herpes simplex virus
      thymidine kinase (TK) promoter in a 1,25-(OH)2D3-dependent fashion. Further
      characterization of these VDREs in various constructs with either a native or TK
      promoter suggests that both VDREs are required for the optimal induction of 24
      hydroxylase expression by 1,25-(OH)2D3.

PMID- 7632728
TI  - Corrigendum to "Cloning, sequence and structural features of a lipase from the
      antarctic facultative psychrophile Psychrobacter immobilis B10" [Biochim.
      Biophys. Acta 1171 (1993) 331-333].

PMID- 7632727
TI  - Different developmental pattern of N-ras and unr gene expression in mouse
      gametogenic and somatic tissues.
AB  - Accumulation of transcripts from N-ras and unr genes was comparatively analyzed
      during the development of germline and somatic tissues. Northern blots on fetal
      and postnatal samples from somatic tissues, including brain, skeletal muscle,
      liver, kidney, small intestine and heart were studied together with ovaries and
      testis. While the expression of N-ras was rather stable all along the development
      of the different tissues analyzed, the expression of unr exhibited a specific
      pattern in some tissues. Specifically, in testis, there is a developmental
      regulation of the relative accumulation of the three alternative transcripts. Unr
      has a relative high expression in testes and heart but the accumulation seems to
      be different for the different size transcripts in each case. However, the
      expression in small intestine is practically absent in adults. From the
      comparative analysis of the expression of both genes, N-ras and unr, we propose
      that the regulation of N-ras is not directly coordinated with unr expression
      during the development. However, the expression of unr and its alternative
      transcripts is developmentally and differentially regulated in small intestine,
      heart and testis. The change in the pattern of accumulation during testis
      development from long to small alternative transcripts, could be interpreted in
      terms of possible alleviation of transcription interference of N-ras.

PMID- 7632729
TI  - Methylene blue-mediated photooxidation of 7,8-dihydro-8-oxo-2'-deoxyguanosine.
AB  - One well known product of the methylene blue-mediated photosensitization of 2'
      deoxyguanosine (dG) in oxygen saturated aqueous solution is 7,8-dihydro-8-oxo-2'
      deoxyguanosine (8-oxodG). We observed that the rate of 8-oxodG photodecomposition
      by methylene blue-mediated photosensitization is approx. 3-times faster than for
      dG. The primary products of the methylene blue-mediated photosensitization of 8
      oxodG are 2-amino-5-((2-deoxy-beta-D-erythro-pentofuranosyl)amino)-4H-imidazol-4
      o ne (dIz), 2,2-diamino-4-((2-deoxy-beta-D-erythro-pentofuranosyl)amino)-5(2H)
      oxazo lone (dZ), the 4R* and 4S* diastereoisomers of 4,8-dihydro-4-hydroxy-8-oxo
      2'-deoxyguanosine (dO), and an as yet unidentified product with a molecular
      weight of 287 (dX). Except for the latter product, these compounds have all been
      identified following the methylene blue-mediated photooxidation of dG. Methylene
      blue-mediated photooxidation of 8-oxodG in D2O instead of H2O leads to a 4-fold
      increase in the rate of 8-oxodG photodecomposition while the addition of sodium
      azide retards the reaction, observations which imply that the reaction occurs via
      a type II (singlet oxygen mediated) mechanism. Like 8-oxodG, dIz and dZ are
      sensitive to hot piperidine and likely contribute to strand breaks observed in
      double stranded DNA exposed to methylene blue plus light followed by hot
      piperidine. Because 8-oxodG generates predominately G-->T transversions, the
      photooxidation of 8-oxodG to dIz, dO, and dX may explain the predominance of G-
      >C transversions in single-stranded M13mp2 bacteriophage DNA exposed to methylene
      blue plus light and then transfected into SOS-induced Escherichia coli.

PMID- 7632730
TI  - Multiple protein complexes, including AP2 and Sp1, interact with a specific site
      within the rat preprotachykinin-A promoter.
AB  - We demonstrate that there is a unique AP2 binding site in the rat
      preprotachykinin-A promoter (rPPT) spanning -865 to -47. AP2 is a transcription
      factor whose expression in sensory neurons has been correlated with rPPT
      expression in these cells. This binding site is adjacent to an element we
      previously identified as binding a single stranded DNA binding protein which was
      also present in sensory neurons. These two complexes encompass a region which we
      had proposed might form a stem-loop structure, allowing binding of the single
      stranded DNA binding protein to the DNA. Here using electrophoretic mobility
      shift analysis we demonstrate that the DNA region corresponding to the putative
      stem-loop structure is bound by a variety of transcription factors, including in
      addition to AP2 the ubiquitous Sp1. DNase 1 footprint analysis demonstrates that
      binding to this domain by the proteins recognising the double-stranded form of
      the cis acting element is mutually exclusive. A promoter fragment containing this
      domain demonstrated a DNase 1 footprint over the 5' region of the stem-loop
      structure. Competition of the binding for this element by an oligonucleotide
      corresponding to the stem-loop structure removed the 5' footprint and exposed a
      new footprint over the 3' region of the stem-loop structure and extending for
      several base pairs. This change in protection observed with DNase 1 digestion
      also correlated with changes of the DNase 1 pattern at specific locations 3' of
      the proposed stem-loop structure. These changes correlated with two DNA sequences
      which were homologous to one another and to a region within the proposed stem
      loop structure. Our results indicate that AP2 could regulate rPPT gene expression
      by a variety of mechanisms.

PMID- 7632731
TI  - Mutational analysis of human U6 RNA: stabilizing the intramolecular helix blocks
      the spliceosomal assembly pathway.
AB  - U6 RNA undergoes several conformational transitions during the spliceosome cycle:
      after the interaction with U4, the singular form of U6 is converted into the U4
      U6 base-paired form, and within the spliceosome, the U4-U6 duplex isomerizes into
      the active U6-U2 conformation. The secondary structure of the singular form
      contains an extended 3' stem-loop, the upper part of which (intramolecular helix)
      most likely reforms in the spliceosome. We have previously shown in the mammalian
      splicing complementation system that the loop and the three adjacent, highly
      conserved base pairs of the intramolecular helix function during both the U4-U6
      interaction and the first step of splicing. Here we demonstrate that the balanced
      stability of the lower, less conserved part of the 3' stem-loop is also critical
      for U4-U6 interaction; however, no specific splicing function could be detected
      in this region. The analysis of the heterologous interaction between mammalian U4
      snRNP and yeast U6 RNA derivatives suggests that there are--in addition to the 3'
      loop and the stability of the intramolecular helix--specific sequence
      determinants in the 3' terminal domain of U6 that are important for efficient
      U4/U6 snRNP assembly.

PMID- 7632732
TI  - Heterologous expression of the highly conserved acidic ribosomal phosphoproteins
      from Dictyostelium (changed from Dictyosteliumm) discoideum in Saccharomyces
      cerevisiae.
AB  - The genes encoding the acidic ribosomal phosphoproteins DdP1 and DdP2 from
      Dictyostelium discoideum have been cloned into yeast plasmid vectors under the
      control of the inducible GAL1 promoter. These constructions have been used to
      transform S. cerevisiae strains D45 and D67 lacking the equivalent ribosomal
      components. The D. discoideum genes are properly transcribed when cells are grown
      in the presence of the inducer galactose and the mRNAs incorporated into
      polysomes. However, the heterologous ribosomal proteins are not able to rescue
      the growth deficiency in S. cerevisiae caused by the absence of their own
      ribosomal proteins. When the heterologous proteins are analyzed using specific
      antibodies, only protein DdP1 is found in the ribosomes of the transformed S.
      cerevisiae D67 strain. No other heterologous protein is found in any other
      transformed strain, suggesting that the heterologous acidic ribosomal components
      are rapidly degraded when they are not bound to the ribosomes. The results
      indicate that D. discoideum DdP1 protein is able to interact with the yeast
      ribosome, though the interaction is functionally inefficient. Protein DdP2, in
      spite of having a higher sequence similarity to its yeast counterparts, is
      completely inactive in S. cerevisiae. Since the P proteins from both organisms
      have extensive amino acid sequence similarity ranging from 60% to 70%, these
      results warns about establishing a direct relationship between the extent of
      amino acid sequence similarity and the capacity of heterologous proteins to be
      functional in host species. Moreover, our data suggest that evolution affected
      the interaction of the acidic proteins with the ribosome rather than the
      structural features responsible for their primary functions.

PMID- 7632733
TI  - Analysis of the linkage between fibronectin alternative spliced sites during
      ageing in rat tissues.
AB  - The modulation of fibronectin (FN) functions in cell-cell and cell-substrate
      interactions in a variety of physiological situations is achieved by the
      selective expression of different isoforms, which in the rat are generated by
      alternatively splicing of at least three regions of the molecule: EIIIA, EIIIB
      and V. Extensive information has been collected on the regulation of the
      differential processing of the single alternatively spliced regions but up to now
      there was scant knowledge about a possible coordinated expression of the three
      regions in the same transcript. Using a long range RT-PCR system we have shown
      that most of the splicing regulation is autonomous for each individual region but
      we have also observed a preferential expression of the EIIIA+ form linked to the
      EIIIB- variant that is age independent. Furthermore the analysis of the single
      regions showed interesting variations occurring in brain during the ageing. There
      is a decrease in the V120 form between the 6- and the 24-month-old rat brain
      (from 57% to 39%), whereas despite a constant prevalence of the EIIIA- form in
      the young rats (65%) there is a random individual variation of this form in the
      old animals. Noteworthy no variations have been detected in the EIIIB region (90%
      EIIIB-). These data suggest a role for the V and EIIIA regions, but not for the
      EIIIB, during the ageing process at least in brain, since no variations were
      detected in kidney between the 6- and 24-month-old animals.

PMID- 7632734
TI  - Close similarity among streptavidin-like, biotin-binding proteins from
      Streptomyces.
AB  - Two strains of Streptomyces venezuelae were found to produce high-affinity,
      biotin-binding proteins, termed streptavidin v1 and v2, respectively. Both
      proteins were isolated to purity, and their corresponding genes were cloned and
      sequenced. Compared to streptavidin from S. avidinii, streptavidin v1 had only a
      single amino acid substitution and streptavidin v2 showed 9 such differences. The
      substitutions were remarkably conservative, none of which affected the amino acid
      residues known to be important to the biotin-binding properties or to the
      structure of the tetrameric protein. The results also indicate that the
      biosynthesis of such biotin-binding proteins is not simply a curious anomaly in a
      single species of Streptomyces. It is suggested that the classification of S.
      avidinii as a unique species should be reconsidered. The occurrence of these
      proteins appears to be linked to the production of an unusual synergistic
      antibiotic complex.

PMID- 7632735
TI  - Two cDNA clones encoding 14-3-3 homologs from tomato fruit.
AB  - Two tomato cDNA clones with homology to the 14-3-3 family of proteins were
      identified through immunoscreening a ripening tomato fruit library (Clontech).
      These two clones share approx. 71% identity at the nucleotide level and 84%
      identity at the deduced amino acid level, with radical amino acid substitutions
      clustering at the acidic carboxy-terminus. Southern hybridization data indicate
      that each clone represents a unique gene. Distinct transcript accumulation
      patterns during tomato fruit ripening together with the homology to brain
      regulatory proteins suggest potential involvement in fruit development.

PMID- 7632736
TI  - The gene from the white-rot fungus Trametes versicolor encoding the lignin
      peroxidase isozyme LP7.
AB  - The structural gene LPGVI (1463 bp including 6 introns), characterized from the
      white-rot basidiomycete Trametes versicolor (PRL 572), encodes a 342-residue
      mature polypeptide of 36.7 kDa, preceded by a 26-residue signal/propeptide. LPGVI
      is identified as the gene encoding the 43 kDa lignin peroxidase isozyme LP7 as
      based on the partial amino acid sequence information available. The polypeptide
      deduced shares 72-74% identity in sequence with other lignin peroxidases and 70%
      with a manganese (II) peroxidase from T. versicolor.

PMID- 7632737
TI  - Cloning and characterisation of a fish aldolase B gene.
AB  - A full length cDNA clone representing an aldolase mRNA was isolated from a sea
      bream (Sparus aurata) liver cDNA library. Sequencing of this clone revealed it to
      encode a 364 amino acid protein with 74% amino acid identity to human aldolase B
      and slightly lower similarity to human aldolase A and C. In view of the sequence
      data and of Northern blot analysis showing strong expression of a 1.6 kb
      transcript in liver it was concluded that the cloned gene represents aldolase B.
      This clone represents the first aldolase gene to be sequenced from any fish
      species thus providing new data on the evolution of the vertebrate aldolase gene
      family.

PMID- 7632738
TI  - A Chlamydomonas homologue to the 14-3-3 proteins: cDNA and deduced amino acid
      sequence.
AB  - We have isolated and sequenced a 1464 bp cDNA from the unicellular green alga
      Chlamydomonas reinhardtii encoding an acidic polypeptide (259 aa) with
      considerable homologies to the 14-3-3 proteins of animals, yeasts and higher
      plants. Like the other members of this highly conserved protein kinase regulatory
      protein family, the deduced amino acid sequence of the Chlamydomonas 14-3-3
      protein includes two putative phosphorylation sites within the N-terminal region
      (positions 62 and 67). Furthermore, an EF hand motif characteristic for Ca(2+)
      binding sites is located within the C-terminal part of this polypeptide
      (positions 208-219). EF hand motifs are also present in the 14-3-3 proteins of
      some higher plants but not in those of animals and yeasts.

PMID- 7632739
TI  - The first nucleotide sequence of an archaeal elongation factor 1 beta gene.
AB  - An archaeal elongation factor 1 beta gene has been isolated for the first time
      from a Sulfolobus solfataricus genomic library. The sequenced clone (869 bp)
      contained two open reading frames, one coding for a protein made of 91 amino acid
      residues (SsEF-1 beta), the other one encoding a nonidentified product (ORF 115).
      The amino acid sequences of segments at the N- and C-terminal of the translated
      SsEF-1 beta were identical to those determined for the native protein. Northern
      and Southern analyses showed that the SsEF-1 beta gene is represented in S.
      solfataricus by a unique sequence. Compared to eubacterial or eukaryal
      corresponding genes the SsEF-1 beta is much shorter.

PMID- 7632740
TI  - Structure of the int-5, a novel MMTV integration genomic locus containing mouse
      early transposon LTR homology region.
AB  - Previous studies have reported the cloning and identification of the int-5, a
      novel mouse mammary tumor virus (MMTV) integration locus involved in mammary
      tumorigenesis. Here we report the characterization of the 5.5 kb region from this
      novel MMTV integration site. Our results show that the region after the MMTV
      integration site, a 258 bp sequence is homologous (100%) to the mouse early
      transposon (mETn) long-terminal repeat and other sequences of the this transposon
      are not present in the 5.5 kb region. Our results also show for the first time
      the tumor specific expression of mETn and expression of the region downstream of
      the MMTV integration site that is homologous to mETn-LTR in D2 mammary tumors.

PMID- 7632741
TI  - Structure of the promoter for the human macrophage stimulating protein receptor
      gene.
AB  - The macrophage stimulating protein receptor is a receptor protein tyrosine kinase
      of the met/hepatocyte growth factor receptor family. Binding of the macrophage
      stimulating protein to its receptor provokes changes in cell morphology and
      motility. Here we report the structure of the promoter of the gene coding for
      this receptor. The major transcription start sites have been identified. The 5'
      flanking region has characteristics of other receptor tyrosine kinase gene
      promoters, namely several GC boxes but the absence of a TATA box. Deletion
      analysis shows that multiple elements are needed for full promoter activity.

PMID- 7632742
TI  - Activity of the promoter of the hsp70 gene of the parasitic helminth Schistosoma
      mansoni in the mammalian CHO cell-line.
AB  - Functional assay of schistosome promoters is problematic because parasite cell
      lines are not available. We found that the hsp70 promoters of S. mansoni and of
      other eukaryotes reveal similarities in the sequence and organization of the
      regulatory elements. Therefore, a construct of the schistosome hsp70 promoter
      linked to the CAT reporter gene was prepared and used to transfect CHO cells. The
      transfected cells showed heat shock dependent activation of CAT. These findings
      indicate that functional evaluation of schistosome promoters can be done, in
      part, in foster cell-lines.

PMID- 7632743
TI  - Identification and analysis of a 'young' polymorphic Alu element.
AB  - A polymorphic Alu element belonging to a young subfamily of Alu repeats has been
      identified. Sequence analysis showed that this Alu element is flanked by perfect
      direct repeats and a 3' oligo(dA)-rich tail. The Alu element, designated A25, is
      deleted by 34 nucleotides at the 5' end and has a single CpG mutation compared to
      the human-specific consensus sequence. Using a PCR-based assay, we demonstrated
      that the A25 Alu repeat is localized to human chromosome 8 and is polymorphic in
      humans.

PMID- 7632744
TI  - Efficacy of smoking cessation strategies in a treatment program.
AB  - Efficacy of a total smoking ban on an inpatient drug and alcohol rehab program
      was assessed by urine cotinine levels and indicated a continued smoking rate of
      70%. In spite of these results, however, some staff were concerned that removal
      of the smoking ban would lead to a dramatic increase in patients' smoking.
      However, other staff were concerned over the apparent dishonesty undermining the
      objectives of the program. Therefore, a change in policy was initiated. Under
      this new approach, where smoking was no longer punished, cotinine levels were 60%
      positive. Although this was not a statistically significant reduction, it was
      clinically significant. Patients were openly encouraged to discuss their smoking,
      and therapies were designed to match patients' level of motivation. A significant
      reduction in number of cigarettes smoked (mean = 26 pretreatment, mean = 17
      posttreatment; p < 0.01), increased interest to stop smoking (on a linear scale
      from 1 to 5, mean = 1.86 pretreatment and mean = 2.61 posttreatment; p < 0.01),
      and increased patient satisfaction was noted in a subsequent sample.
      Nonprohibitive counseling approaches were just as effective as prohibition of
      smoking. Change in smoking behavior and motivation were demonstrable with
      programming that emphasized behavior change and motivational counseling.
      Relationships between nicotine dependence, depression and other substance use
      disorders are discussed.

PMID- 7632745
TI  - Pharmacotherapy in alcoholism.
AB  - This review categorizes five main uses of pharmacologic agents in the treatment
      of alcoholism: reversing the active pharmacologic effects of alcohol; controlling
      withdrawal symptoms; blocking the desire for alcohol use; treating psychiatric
      symptoms induced by alcohol and other drugs; and treating independent, but
      concurrent, psychopathologic conditions. No medication, including stimulants such
      as caffeine, has been found to actually reverse the action of alcohol. Because of
      their cross-tolerance and dependence with alcohol, benzodiazepines--especially
      intermediate acting preparations such as chlordiazepoxide and diazepam--are the
      mainstay in treating alcohol withdrawal, including convulsions and delirium
      tremens. Studies suggest that serotonin uptake inhibitors such as zimelidine,
      citalopram, viqualine, and fluoxetine may reduce alcohol consumption and that is
      not an antidepressant effect. Naltrexone, an opioid antagonist, also may be
      effective in reducing the urge to drink. The major aversive agent to alcohol in
      clinical use is disulfiram. When an independent psychiatric disorder accompanies
      alcoholism or drug addiction, it may require treatment, including
      pharmacotherapy, as the addiction is also being treated with nonpharmacologic
      methods such as abstinence-based treatment programs.

PMID- 7632746
TI  - Alcohol use and injury severity in trauma patients.
AB  - Trauma is one of the leading causes of morbidity and mortality in the U.S. and
      alcohol makes a significant contribution to this problem. Alcohol has been
      demonstrated to increase the incidence of trauma through its ability to alter
      behavior and impair motor performance. Its effect on the severity of trauma has
      been more controversial. This study examines the impact of acute intoxication on
      injury severity by retrospectively reviewing 12 months of trauma admissions (n =
      1957) to a Level I trauma center for Injury Severity Score, mortality rate,
      discharge destination and length of hospital stay. When intoxicated versus non
      intoxicated patients were compared, no differences were found in ISS, mortality,
      or incidence of being discharged to home. However, length of stay was
      significantly shorter for intoxicated patients. This study supports the concept
      that acutely intoxicated trauma victims suffer as many consequences as non
      intoxicated patients, with the exception of length of stay. A discussion of these
      findings along with other reports on injury severity and alcohol use is included
      at the end of the paper.

PMID- 7632748
TI  - Cocaine abuse in methadone maintenance patients is associated with low serum
      methadone concentrations.
AB  - Cocaine abuse in methadone maintenance patients has emerged as a significant
      clinical problem. To determine if raising the daily methadone dosage is an
      effective way to eliminate cocaine abuse, 74 methadone maintenance patients
      maintained at daily dosages between 30 and 80 mg and who chronically abused
      cocaine were studied by a standard protocol. A total of 21 (28.4%) subjects
      ceased cocaine abuse when their methadone dosage was progressively raised to a
      maximal daily dose of 160 mg. Cocaine abuse appeared to accelerate elimination of
      methadone, since inadequate methadone serum concentrations (below 100 ng/ml) were
      found in 48 of 67 (71.6%) subjects tested 24 hours after a 100 mg oral methadone
      dose. Although cocaine abuse in methadone maintenance patients may respond to
      raising the daily methadone dosage, alternative treatments for cocaine abuse in
      methadone maintenance patients must be identified since cocaine abuse may lower
      serum methadone concentrations.

PMID- 7632747
TI  - Tuberculosis surveillance in a therapeutic community.
AB  - Tuberculosis, a chronic communicable bacterial infection of epidemic proportions
      in the United States, is more common among debilitated and immunocompromised
      persons, for example, alcoholics, drug abusers, and HIV/AIDS patients, than among
      the general population. Daytop Village Inc., a drug free therapeutic community
      for chemical dependency treatment, initiated a program of tuberculosis (TB)
      surveillance and prevention education with grant support. Continuous educational
      sessions for staff and residents have raised awareness of the threat of TB. From
      March 1991 until September 1992, 2,932 clients screened for TB found 272 (9.2%)
      PPD positive. Of these 272, 125 also tested for HIV found 28 (22.4%) HIV
      positive. The TB screening program had no negative impact on the retention rate
      of Daytop residents. With sufficient fiscal and personnel support, tuberculosis
      education, screening, and treatment has been naturally integrated into the
      primary care agenda within the therapeutic community model of drug abuse
      rehabilitation.

PMID- 7632750
TI  - Utilization of plasma and urine methadone concentration measurements to limit
      narcotics use in methadone maintenance patients: II. Generation of plasma
      concentration response curves.
AB  - Controversy exists still concerning the proper daily dose of methadone required
      to eliminate illicit narcotics use. To address this, urine methadone and opioid
      concentrations were measured prospectively (150 maintenance patients, 18 month
      period, 9250 urine samples) using fluorescence polarization immunoassay. Results
      demonstrate that current thresholds (EMIT uses 300 micrograms/L) defining opiate
      positive urines are overly high (FPIA can go as low as 25 micrograms/L), causing
      severe underestimation of opioid use in the typical clinic. Using this data,
      plasma methadone concentration and dose response probability curves were
      generated for illicit opiate use. Results demonstrate a S-shaped, 24 hr trough
      plasma methadone concentration response curve with effective concentrations, EC90
      = 80 micrograms/L, EC98 = 600 micrograms/L. Plotting mean plasma methadone
      concentration versus dose gives a monotonically increasing function: Conc =
      5.367*dose0.858, raw R-squared = 0.967, corrected R-squared = 0.802.
      Unfortunately, coefficients of variation for plasma concentrations at each
      prescribed dose are unacceptably large, explaining poor dose response
      relationships for some patients.

PMID- 7632751
TI  - 8th International Symposium on Radiopharmacology. Proceedings. Ghent, Belgium,
      September 5-9, 1993.

PMID- 7632749
TI  - Addiction severity, psychopathology and treatment compliance in cocaine-dependent
      mothers.
AB  - A retrospective chart review of clinical assessments encompassing psychiatric
      diagnosis, addiction severity and psychosocial functioning of cocaine-dependent
      pregnant or postpartum women during inpatient treatment was obtained. Predictive
      value of the elements of the assessment battery on aftercare compliance was
      determined. METHODS: The charts of forty-one cocaine-dependent pregnant or
      postpartum women treated for substance abuse were reviewed for addiction severity
      and aftercare compliance. Thirty of these patients were administered the
      Structured Clinical Interview for DSM-III-R (SCID I and II) and screened for
      history of victimization during inpatient treatment. All women were divided into
      two groups, aftercare treatment compliers (TCs) and aftercare treatment
      noncompliers (TNCs). TCs were those patients who attended at least one-half of
      the aftercare sessions. RESULTS: TCs had significantly lower scores on the
      psychiatric (p < or = .05) and employment (p < or = .01) subscales of the ASI,
      indicating lesser problem severity. The total composite mean ASI score, although
      not statistically significant, was also lower for TCs. Of the thirty subjects
      that were administered the SCID-I and II, sixty-seven percent had an Axis I
      disorder. TNCs were significantly more likely to have an anxiety disorder (p < or
      = 0.05). Eighty percent of subjects had at least one Axis II disorder. TNCs were
      also significantly more likely to have any Axis II disorder (p < or = 0.05), and
      to have Cluster B and Cluster C personality disorders (p < or = 0.05). In
      addition, seventy-three percent of subjects reported victimization, with TNCs
      significantly more likely (p < or = 0.05) to have experienced childhood abuse.
      CONCLUSIONS: In this sample of pregnant cocaine using women, the majority of
      women had current Axis I and II disorders as well as history of victimization.
      The results suggest that the ASI employment and psychiatric subscales may be
      predictive of aftercare compliance. The presence of certain Axis I and/or Axis II
      disorders also appear to be predictors of poor compliance. Treatment of pregnant
      substance using women must be designed to address issues of victimization as well
      as psychiatric disorders.

PMID- 7632752
TI  - Scintigraphic determination of the biodistribution of an 111In-labelled poly(L
      lysine) backbone branched polypeptide drug carrier in tumour-bearing mice.
AB  - A branched polypeptide drug carrier, with a poly(L-lysine) backbone, has been
      labelled with 111In and its biodistribution imaged in mice with transplanted B16
      melanoma. Levels of tracer in tumours were not great enough for tumours to be
      discerned on gamma-camera images, and this was confirmed by subsequent dissection
      analysis. Tumour levels of 111In from labelled polymer were about 3% of the dose
      g-1 two days after injection. Similar levels of tracer were found in tumour
      tissue of mice injected with mouse immunoglobulin or serum albumin labelled with
      111In by DTPA chelation, or injected with free 111In-chloride to label serum
      transferrin. There was rapid excretion of a sub-component of the 111In-labelled
      polymer visible in the images. Gel permeation chromatography suggested that the
      polymer was heterogeneous, some components having Stoke's radii below that
      allowing renal clearance. Gel permeation chromatography was used to separate
      labelled polymer into fractions having high, intermediate and low renal
      clearance. The low-excretion fraction showed a two-fold increase in tumour
      levels, compared with native polymer, although as this fraction showed greater
      survival in the blood and body as a whole, discrimination between tumour and
      normal tissue was not increased.

PMID- 7632753
TI  - Oxamniquine: a labeling procedure with technetium-99m and a biodistribution study
      in mice.
AB  - Oxamniquine (OXY), a tetrahydroquinoline derivative, is used as an
      antischistosomal drug and generally has been labeled with carbon-14 and tritium.
      We decided instead to label it with technetium-99 (99mTc). In order to determine
      the optimal conditions, different concentrations of this drug were incubated with
      various stannous chloride solutions. We then added 99mTc, and chromatography was
      performed using 0.9% NaCl solution, acetone and 1.2N HCl as the mobile phase.
      Using a solution of 1.0 mg/mL stannous chloride and 0.5 mg/mL oxamniquine, over
      94% of the radioactivity bound to oxamniquine (99mTc-OXY). In the biodistribution
      study, 99mTc-OXY was administered in mice intramuscularly, orally and
      intravenously. When the intramuscular route was used, the main uptake (after 30
      minutes) of the labeled drug was in the kidneys, liver and intestines; after 240
      minutes the labeled drug was still found in the liver and kidneys, but at
      increased levels in the intestines. It was also present in the faeces. When the
      oral route was employed, labeled OXY was mainly found in the stomach after 30
      minutes, but there was a decrease after 240 minutes. During this period
      radioactivity increased in the intestines. When the intravenous route was
      employed the labeled OXY was found in the liver and spleen. The radioactivity
      decreased with time in these organs. Using infected animals, radioactivity was
      found in isolated worms.

PMID- 7632754
TI  - Gamma scintigraphy in the delivery, biodistribution and targeting of therapeutic
      agents.
AB  - The established clinical role of radionuclide imaging includes the diagnosis and
      monitoring of a wide range of clinical conditions. The therapeutic use of
      radionuclides has centred on a relatively small number of pathological
      conditions, particularly within the field of oncology. More recently there has
      been growing interest in the use of radionuclide imaging in drug evaluation and
      research (RIDER). Studies have been undertaken in order to increase the
      understanding of the in in vivo behaviour of pharmaceutical dosage forms in
      addition to the in vivo behaviour of molecular and cellular anti-tumour agents.
      The imaging facilities required for such undertakings are available in most
      nuclear medicine departments, although the expertise for radiolabelling and the
      requirements for the production of drug conjugates and pharmaceutical
      formulations are limited to a small number of centres. This paper discusses the
      application of radionuclide imaging in drug research with particular reference to
      the role of gamma-scintigraphy in monitoring the biodistribution and
      pharmacokinetics of immune mediated drug conjugates intended for the treatment of
      malignant disease. Examples described include the evaluation of oral and inhaled
      drug delivery systems and the biodistribution and in vivo kinetics of parenteral
      administrations.

PMID- 7632755
TI  - The role of nuclear medicine procedures in the functional characterization of
      patients: exclusive, complementary or alternative to other technologies?

PMID- 7632757
TI  - Therapeutic drug monitoring can avoid iatrogenic alterations caused by 99mTc
      methylene diphosphonate (MDP)-gentamicin interaction.
AB  - Gentamicin is an aminoglycoside antibiotic used to treat a wide variety of
      infections caused by gram-negative organisms, but it is potentially toxic to the
      kidneys. Due to its nephrotoxicity, gentamicin may cause abnormal renal uptake to
      be seen on 99mTc-MDP bone scintigraphy. The presence of the radiopharmaceutical
      in the kidneys, along with an increase in renal retention, tend to produce
      scintigraphic results that falsely identify characteristics related to diseases
      such as renal vascular, or urinary tract obstruction, and even renal cancer. An
      altered biodistribution may provide misleading information that can either mask
      or mimic certain disease symptoms. A method to maximize the therapeutic benefit
      of gentamicin while minimizing the risk of nephrotoxicity and the appearance of a
      hot kidney on scintigraphy is desirable. Serial pharmacokinetic dosing has been
      proposed as a method to accomplish this goal. Therapeutic drug monitoring (TDM)
      of gentamicin therapy, and bone scintigraphy employing 99mTc-MDP as the
      radiopharmaceutical was carried out in 22 patients. The data presented here
      demonstrate that with serial pharmacokinetic dosing of gentamicin, the iatrogenic
      alteration caused by gentamicin therapy can be avoided.

PMID- 7632756
TI  - [123I] beta-CIT, a tracer for dopamine and serotonin re-uptake sites: preparation
      and preliminary SPECT studies in humans.
AB  - beta-CIT (2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane) is a new ligand that
      has a high affinity to dopamine and serotonin re-uptake sites. [123I] beta-CIT
      was prepared by reacting the corresponding trimethylstannyl precursor with no
      carrier-added 123I. Iodogen was used as an oxidizing agent. The labeling mixture
      was purified by filtration through a mini-column. The purity of the product was
      confirmed by analytical HPLC. The total radiochemical yield was 67 +/- 5%. The
      radiochemical purity was > 95% and the specific activity was > 107 GBq/mol (>
      2900 Ci/mmol). The final product was confirmed to be free of endotoxins before
      intravenous administration. Two healthy male volunteers were injected iv with 120
      160 MBq of [123I] beta-CIT and scanned with a 3-head gamma-camera (Siemens
      MultiSPECT3). Dynamic SPECT scans were performed for up to 2 hours. There was a
      high accumulation of radioactivity in the striatum and in the thalamus, and some
      in the medial prefrontal area. Thus, we have developed an easy method to prepare
      [123I] beta-CIT with a high specific radioactivity and in a sufficient
      radiochemical yield. Specific [123I] beta-CIT binding in striatal and thalamic
      regions was demonstrated in humans. [123I] beta-CIT is a potential marker of the
      dopamine and serotonin transporters and can be used to study the pathophysiology
      of Parkinson's disease, as well as neuropsychiatric disorders.

PMID- 7632758
TI  - A pharmacokinetic comparison of murine and chimeric forms of the 99mTc-labelled
      174H.64 monoclonal antibody.
AB  - The monoclonal antibody (MoAb) 174H.64 (Truscint SQ, Biomira Inc.) is a murine
      derived MoAb reacting with an extracellular surface component of the cytoskeletal
      matrix ectopically expressed on squamous-cell carcinoma cell-surface membranes. A
      chimeric form of this MoAb has also been produced by genetically modifying the Fc
      portion of the MoAb by the insertion of a human Fc fragment. During this process
      the isotype was altered from an IgG1 (murine) to an IgG3 (chimeric). Pilot and
      phase I/II clinical trials of the murine and chimeric 99mTc-labelled 174H.64
      MoAbs have been undertaken at selected European and North American sites. As part
      of this evaluation serum, urine and image data were collected at specific time
      intervals and used to obtain a kinetic model to describe the in vivo distribution
      of the MoAbs. A two-compartment model of the form: C(t) = C1 e-lambda 1t + Cz e
      lambda zt was found to best describe the serum distribution of radioactivity of
      both the murine and chimeric MoAbs. The initial distribution half-lives were 2.9
      +/- 0.7 hours and 2.7 +/- 0.2 hours, and the terminal elimination half-lives were
      17.6 +/- 3.8 hours and 22.5 +/- 1.3 hours for the murine and chimeric MoAbs,
      respectively. No significant difference was found between the kinetic model
      parameters of two MoAbs at the 95% level. Assuming a similar clinical efficacy,
      these MoAbs could then be used interchangeably, with the chimeric MoAb offering
      potential advantages in reducing HAMA response.

PMID- 7632759
TI  - Biodistribution and pharmacokinetic screening in humans of monoclonal antibody AR
      3 as a possible immunoscintigraphy agent in patients with pancreatic cancer.
AB  - This pharmacokinetic study was performed in order to assess the potential
      usefulness of the murine monoclonal antibody (MoAb) AR-3-IgG1 as an
      immunoscintigraphy agent for pancreatic cancer. This MoAb, which defines a mucin
      like antigen (CAR-3) expressed by a large fraction of pancreatic cancers, shows
      in fact favourable in vivo localizing properties in the experimental animal model
      of human tumor xenograft. 131I-AR-3-IgG1 was injected i.v. into 5 patients with
      suspected pancreatic cancer. Whole-body maps and spot views of the abdominal area
      were recorded with a computerized gamma-camera, and specific regions of interest
      drawn over the liver and spleen helped to define the kinetics of activity in
      these organs. Blood samples taken from 0.1-144 hours post-injection and daily
      urine collections over the same interval served to define the kinetics of plama
      distribution and removal of activity from the body. Different multicompartmental
      models were tested to fit the experimental data, assuming as the starting
      hypothesis that there was to be significant nonspecific tracer accumulation in
      the liver, spleen and bone marrow, as already observed for the majority of
      radioiodinated murine MoAbs injected into humans. Surgery confirmed pancreatic
      cancer in 3 out of the 5 patients (chronic pancreatitis and periampullary cancer
      in one each); in all these 3 patients immunostaining with the MoAb AR-3
      demonstrated the presence of the CAR-3 antigen (with a cytoplasmic and
      endoluminal/secretory pattern of distribution). Nonspecific radioactivity
      accumulation in the liver, spleen and bone marrow was extremely low, linked
      essentially to the blood pool effect of circulating activity in these
      organs.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7632760
TI  - A new method for site-specific labelling of the oligosaccharide chain of
      antibodies: preliminary results.
AB  - There are various approaches for improving endoradiotherapy and diagnosis with
      monoclonal antibodies in nuclear medicine. The known methods of site-specific
      labelling of biomolecules based either on reactions with sulfhydryl groups or on
      reactions with aldehyde groups of the oligosaccharide chains effect unwanted
      alterations of the biomolecules. We present a new method to introduce radioactive
      halogens into the oligosaccharide chains of an antibody, based on the enzymatic
      transfer of the labelled synthetic sialic acid derivative CMP-9-deoxy-9-salizoyl
      NeuAc. It was first labelled by the iodogen-method (iodine) in yields of more
      than 90%. Under selected conditions it was possible to obtain di- and
      trihalogenated products. Then the radioactive sialic acid derivatives were
      transferred during 90 minutes at room temperature with 2.6-sialyltransferase from
      rat liver into the oligosaccharide chains of antibodies. It is necessary to use
      neuraminidase pretreated antibodies with an increased number of binding sites for
      sialic acid derivatives. Yields of about 55% were obtained for the monoiodinated
      sialic acid derivative. With this method we present a reasonable alternative
      reaction of labelled compounds with biomolecules. Studies of the immunoreactivity
      are now in progress.

PMID- 7632762
TI  - Nickel-57-doxorubicin, a potential radiotracer for pharmacokinetic studies using
      PET: production and radiolabelling.
AB  - The clinical use of anthracyclines, such as doxorubicin (DXR), is hampered by
      tumour development of multidrug resistance (MDR). The drug efflux associated with
      MDR could be characterised in vivo using Positron Emission Tomography (PET) in
      conjunction with a suitable radiolabelled drug. We are investigating DXR labelled
      with the positron emitter 57Ni as a potential analogue of the parent drug.
      Essential to this work is the production of a high purity radionuclide in a
      suitable chemical form for the preparation of radiolabelled DXR. To optimise
      production parameters, excitation functions (reaction cross section as a function
      of beam energy) for proton induced reactions in cobalt were measured up to 60
      MeV. The excitation function for the 59Co(p,3n)57Ni reaction shows a maximum
      cross section of 13.8 +/- 1.5 mb at 38 MeV. The optimum energy range for
      production of 57Ni was found to be 41-->26 MeV resulting in an experimental thick
      target yield of 17.8 MBq/muAh. The level of the 56Ni impurity is only 0.21% at
      the end of bombardment. A radiochemical procedure, based on cation-exchange
      chromatography, has been developed for the separation of radionickel from the
      cobalt target and other radiochemical and chemical impurities. The 57Ni activity
      was eluted, using 2M HCl, from a Dowex-50Wx8(H+) column, in a 95% radiochemical
      yield. Optimum labelling of DXR has been investigated in terms of pH, reaction
      time and temperature, achieving radiochemical yields > 94%. DXR labelled with
      57Ni therefore shows promise as a radiotracer for pharmacokinetic studies using
      PET.

PMID- 7632763
TI  - Is technetium-99m the radioisotope of choice for radioimmunoscintigraphy?

PMID- 7632761
TI  - In vivo behavior of 111In-labeled monoclonal anti-prostatic acid phosphatase
      antibody after intraprostatic and intravenous injections.
AB  - The 111In-labeled monoclonal anti-prostatic acid phosphatase (PAP) monoclonal
      antibody F(ab')2 fragment was used for the radioimmunodetection of prostate
      cancer in two different patient groups: 15 patients with surgically verified T1-2
      prostate cancer were imaged prior to staging lymphadenectomy and total
      prostatectomy using lymphatic administration (intraprostatic (ipr) injection),
      and 15 patients with verified metastatic prostatic cancer were imaged after
      intravenous (i.v.) injection. The patients were studied on several occasions (at
      0-180 hours) after injecting a 1 mg MoAb fragment labeled with 75-150 MBq111In
      (DTPA-chelation). The extirpated tissues were counted for radioactivity, and
      studied immunohistochemically (IHC) and histologically. The anti-PAP MoAb was
      labeled with high efficiency (87-99%) and it demonstrated good immunoreactivity
      (90-95%) and a high affinity to the target antigen. In the excised prostates, cut
      into 12-18 smaller pieces, there was a clear correlation between the PAP content
      (as detected by IHC) and absolute radioactivity (% ID of 111In anti-PAP/g
      prostate). However, there was no correlation between radioactivity and the amount
      of cancer tissue (% of histological slices) inside the removed prostate tissue.
      In the pharmacokinetic studies, maximum activity in the serum was obtained within
      3-5 hours after ipr injection; after that the kinetic behavior was similar to
      that after i.v. injection. After i.v. injection, two components could be
      distinguished the pharmacokinetic curves; the half-lives for mean distribution
      and elimination were 0.62 and 35.6 hours, respectively. The mean distribution
      half-life as well as the AUC from the pharmacokinetic curves correlated
      significantly with serum PAP (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7632764
TI  - Radiopharmacokinetics: methods and prospect.

PMID- 7632765
TI  - Direct labeling of monoclonal antibodies with 99mTc and radioimmunodetection of a
      murine mammary carcinoma with 99mTc-B2C114.
AB  - Two anti-CEA antibodies, B2C114 and IORCEA1, were radiolabeled with 99mTc by two
      direct methods (mercaptoethanol and ascorbic acid reduction), and the radio
      immunoimaging properties of B2C114 were assessed in mice bearing an M3-reactive
      tumor. The labeling efficiency was greater than 90% as measured by ITLC in
      saline, methylethylketone and with serum albumin impregnated sheets using
      ethanol: water: NH4OH (2:5:1). The label was stable to challenge with excess
      DTPA, and in the case of ascorbic acid reduction, serum analysis showed that 10
      15% of the radioactivity was lost during incubation. In vitro studies
      demonstrated that the radiolabeled antibodies retained their immunoreactivity.
      Biodistribution studies in normal Balb/c mice showed that the pattern of uptake
      was quite similar for both antibodies. Biodistribution of the 99mTc-B2C114 and
      image studies in the animal model showed that the tumor was clearly visualized
      and that B2C114 labeled with 99mTc is a possible candidate for human
      radioimmunodetection of CEA-expressing tumors.

PMID- 7632766
TI  - Comparison of the radiochemical behaviour and biological efficacy of three 99mTc
      HIG preparations.
AB  - The aim of the present study was to evaluate whether the different methodologies
      used for human polyclonal immunoglobulin (HIG) preparation can affect the
      radiochemical purity of 99mTc-HIG and its binding affinity to infection sites.
      Three intravenous immunoglobulin preparations, beta-propiolactone treated,
      hydrochloric acid/pepsin treated, and an unmodified HIG molecule were studied.
      The HIG preparations were analysed by size-esclusion HPLC. The UV chromatogram
      profiles obtained showed some percentage of polymeric and dimeric fractions in
      all of them. The three HIG studied were directly radiolabelled via 2
      mercaptoethanol reduction. Lyophilized kits containing 1 mg of HIG and a small
      amount of MDP(Sn) solution were prepared and then radiolabelled by adding
      pertechnetate-99m. The radiolabelled products, evaluated by ITLC, showed high
      radiochemical purity and in vitro stability. Biodistribution studies were
      performed in mice with an infection in the right thigh induced by the im
      administration of a single isolate of S. aureus, in order to compare the ability
      of 99mTc-HIG to detect an infectious focus. This study suggests that any damage
      during immunoglobulin treatment can influence the in vivo behaviour of 99mTc-HIG.

PMID- 7632768
TI  - Influence of radiolabel on the in vivo processing of intact and fragmented anti
      tumour monoclonal antibody.
AB  - The anti-colon carcinoma MoAb35 and its F(ab')2 fragment were labelled with 131I
      or 67Cu and their biodistributions compared in nude mice bearing human tumour
      xenografts. Two-fold higher levels of 67Cu were found in the xenografts than
      131I, with no significant difference in whole-body distribution. For the F(ab')2
      fragment tumour levels were not significantly different between 131I and 67Cu. A
      very high accumulation of 67Cu was found in the kidney (36.7% ID/g). Whether
      deiodination in the kidney could account for the difference in nuclide
      accumulation was checked by repeating the study with 131I, linked to the F(ab')2
      by a method known to resist deiodination. The results showed a slight increase in
      tumour accumulation of 131I but kidney levels remained low at 3.1% ID/g 24 hours
      post-injection compared to 42.4% ID/g for 67Cu, suggesting that deiodination does
      not play a role in the observed low levels of 131I in the kidney. Ongoing studies
      on the distribution and processing of radioimmunoconjugates will hopefully assist
      in their application in clinical studies.

PMID- 7632767
TI  - Evaluation of a 99mTc-antimyosin kit for myocardial infarct imaging.
AB  - The Fab fragment of a mouse monoclonal antibody AM(3-48) that recognizes alpha
      and beta-heavy chains of human atrial and ventricular myosin and beta-heavy chain
      of human slow skeletal muscle myosin [CardioVisionTM] was labeled with 99mTc
      using stannous reductant in a simple, instant kit method. The infarcted heart
      uptake in dogs of 99mTc-AM(3-48)Fab' was compared with that of established
      radiopharmaceuticals routinely used for cardiac imaging in humans. The dog
      infarct was induced by bringing a catheter from the femoral artery to the
      coronary artery where an artificial blood clot was generated. The 99mTc-AM(3
      48)Fab' preparation was selectively taken up by infarcted myocardium, resulting
      in diagnostic quality images of the infarcted area as early as 6 hour post
      injection, rendering CardioVisionTM particularly useful for SPECT imaging. Good
      agreement was found between the images obtained with 99mTc-Pyrophosphate and
      those obtained with 99mTc-AM(3-48)Fab', while the infarcted area was clearly
      delineated as a cold spot with 99mTc-MIBI or 201 Tl-thallous chloride. The
      biodistribution of 99mTc-AM(3-48)Fab' was also studied in healthy and
      isoproterenol-infarcted rats, from which dosimetry values in man were
      extrapolated. The data indicate that the kidneys will receive the highest
      radiation dose and that they will be the main contributors to the total radiation
      burden, which was estimated at 0.005 rad/mCi.

PMID- 7632769
TI  - Biodistribution and estimated radiation burden for a new 123I-labelled monoamine
      oxidase-B inhibitor, Ro 43-0463: a preliminary report.
AB  - The selective, reversible inhibitor of monoamine oxidase B (MAO-B), Ro 19-6327
      (Lazabamide) N-aminoethyl-5-chloro-picolinamide, inhibits the enzyme with an
      initial competitive phase, followed by a time-dependent inhibition of MAO-B; i.e.
      Ro 19-6327 is a substrate for MAO-B, and after its oxidation it is activated into
      an intermediate form which remains tightly bound to the enzyme's active site. Our
      radiopharmaceutical is a new 123I-labelled derivative of Ro 19-6327, N-aminoethyl
      5-[123I]iodo-picolinamide, which seems to be a potentially useful SPECT tracer
      for the imaging of the MAO-B enzyme distributions. The first biodistribution of
      this compound was measured in rats at 6 different points in time (10, 25, 40, 60,
      180 and 900 minutes post-injection). For each point the average from three
      animals was taken. In the brain there was an activity plateau over the first
      hour. In the first hour post-injection the brain-to-blood ratio was over 1, with
      a maximum ratio of 1.24 at 25 minutes post-injection. Because MAO-B is abundant
      in the ependyma, pineal and cerebellar Bergmann glia cells, this ratio of 1.24
      over the whole brain is encouraging. At first, radioactivity was principally and
      rapidly accumulated in the liver. After 1 hour, about 37% of the injected
      activity is accumulated there. The elimination of the compound seemed to take
      place mainly through the hepatobiliary system (about 75%), but also via the
      kidneys (about 25%). Fifteen hours post-injection, only 4% (corrected for decay)
      of the injected radioactivity was left in the body.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7632771
TI  - Synthesis and biological evaluation of the four isomers of 99mTc
      cysteinyltriglycine, an amino substituted derivative of 99mTc-MAG3.
AB  - Cysteinyltriglycine (CYSG3) is a derivative of MAG3 in which the mercaptoacetyl
      group is replaced by a cysteinyl moiety. This implies the presence of a primary
      amino group on the ligand, as in case of p-amino-hippuric acid, the compound with
      the highest renal tubular secretion known. The present study was undertaken to
      investigate the influence of this amino group on the biological behaviour of
      complexes of 99mTc with MAG3-like molecules. The L- and D-isomers of
      cysteinyltriglycine were synthesized as S-benzyl N1-CBO protected precursors.
      After removal of the protective groups with Na/NH3, the isomers were labelled
      with 99mTc. This resulted in the formation of two diastereomeric complexes (A and
      B in the order of HPLC-elution) for each of them. The biodistribution of the four
      HPLC-purified isomers was tested in mice. Isomers DA and LB showed slightly
      superior or similar renal excretion characteristics compared to 99mTc-MAG3,
      whereas the two other isomers were cleared at a lower rate by the kidneys and
      more through the liver and the intestines. The results indicate that substitution
      of 99mTc-MAG3 with an amino function may somewhat improve the rate of renal
      excretion, but the configuration of the 99mTc-labelled complexes appears to be
      more important to its biological behaviour.

PMID- 7632770
TI  - Kinetics of a new iodolabeled MAO-B inhibitor in the rat brain and in cultured
      astrocytes.
AB  - 3-Bromobenzyloxy phenyloxy hydroxymethyl propanol was labelled with iodine-125.
      Labeling yield was approximately 92%. Using HPLC and an RP18 column, Iodo*MD (MW
      = 412) was obtained at no-carrier-added conditions (specific activity 125
      Ci/mmole). Biochemical experiments were carried out in vitro and showed a Ki for
      MAO-B of 5.4 nM and of 5000 for MAO-A (RA/B = 926). Using ex vivo kinetic
      inhibition in rat (dose: 5 mg/kg p.o.), the results demonstrated a strong
      similarity of action with BromoMD and IodoMD, with an inhibition percentage that
      decreased with time (91% at 1 hour, 48% at 8 hours, 2% at 24 hours). The rat
      brain Iodo*MD concentration was maximal after the first pass and inhibition
      decreased slowly with time (T1/2 = 1.8 hours). Uptake and wash-out of Iodo*MD was
      studied on two-day-old rat astrocytes in culture. Half-times of uptake and efflux
      were respectively 2.5 minutes and 7.5 minutes. The use of metabolic inhibitors
      (KCN and Digoxin) suggested the absence of any active transport. Binding studies
      with various concentration of cold MD 360194 showed that at 10(-8) M the uptake
      decreased significantly. Rats were dissected at different times post i.v.
      injection (0-2 hours), and the principal organs and brain were obtained (the
      brain was separated into 7 pieces). Radioactivity was concentrated mainly in the
      liver (24.6 +/- 4%), fat (12.4 +/- 3.4%) and muscles (18.4 +/- 3%). In the brain
      the concentration was approximately 1.2 +/- 0.3% within 30 minutes post i.v.
      injection and 0.84 +/- 0.15% thereafter. The hypothalamus and striatum were two
      fold more active than the cortex.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7632772
TI  - Labelling of poly-L-lysine with 99mTc and evaluation as a possible tracer agent
      for ventriculography.
AB  - A stable 99mTc-labelled compound that is easy to prepare and that is retained for
      a long period of time in the blood would constitute an ideal replacement for
      99mTc-HSA (limited by its rapid diffusion) and 99mTc-erythrocytes (lengthy and
      risky in vitro labelling) as tracer agent for ventriculography. We investigated
      whether 99mTc-labelled polymers would be suitable for this purpose. Four types of
      poly-L-lysine (PL) (Mw 41,000 to 377,000) were used either in underivatized form
      labelled at pH 12, or derivatized with a varying number of mercaptoacetyl (MA)
      substituents by reaction with N-hydroxysuccinimidyl-S-acetylmercaptoacetate
      followed by deprotection with hydroxylamine and labelling at pH 7.5. A high
      labelling yield was obtained in all cases. HPLC-purified 99mTc-PLs and 99mTc-MA
      PLs were evaluated in mice, with 125I-HSA as an internal biological standard. The
      retention in the blood at 10 minutes and 60 minutes p.i. was not higher than
      about 30% for any of the tested compounds versus 84% for 125I-HSA, and was only
      10% for the smallest 99mTc-labelled PL and MA-PL. Liver uptake was high for the
      99mTc-PLs, whereas the 99mTc-MA-PL's were excreted in significant amounts to the
      urine. It is concluded that 99mTc-labelled poly-L-lysines or polymercaptoacetyl
      poly-L-lysines are not suitable as blood pool tracer agents.

PMID- 7632773
TI  - Radiopharmacological evaluation in dogs of a new renal function agent.
AB  - The hydrophilic penta-anionic complex [Technetium (Carboxymethylisocyanide)6]-5,
      [Tc(CNCH2COO-)6]-5 (Tc-CAMI) was synthesized to evaluate its potential as a renal
      function imaging agent. The compound contains six distally arranged carboxyl
      groups that can act as substrates for the organic acid receptor of the renal cell
      to effect tubular secretion of this agent. Dynamic gamma-camera imaging of 99mTc
      CAMI was performed in normal dogs to compare its bio-distribution and
      pharmacokinetics with those of proven tubular secretion (99mTc-MAG3) and globular
      filtration (99mTc-DTPA) agents. The relative difference between the observed mean
      renal transit times (MRTT) of 99mTc-CAMI and 99mTc-MAG3 was 0.15 compared with
      1.24 for 99mTc-CAMI and 99mTc-DTPA. Pathological models of obstructive uropathy,
      renal arterial stenosis and renal denervation were produced in the same animals
      to demonstrate the diagnostic potential of the agent. These experiments and data
      showing that probenecid competes with 99mTc-CAMI for renal transport indicate
      that this compound functions as a tubular secretion agent and may be useful for
      monitoring renal function in various disease states.

PMID- 7632775
TI  - Tissue blood flow estimation with copper(II)-pyruvaldehyde bis (N-4
      methylthiosemicarbazone) and PET.
AB  - Copper (II)-pyruvaldehyde bis (N-4-methylthiosemicarbazone) (Cu-PTSM) labelled
      with 62Cu or 64Cu is currently under investigation as a radiotracer for imaging
      the distribution of blood flow with positron emission tomography (PET). The
      application of a simple trapped tracer model in conjunction with tissue uptake
      and continuous arterial sampling to estimate blood flow has been compared with
      the 57Co-microsphere method in the rat. After intraventricular injection the
      cumulative arterial function for 64Cu increased progressively due to the presence
      of circulating non lipophilic complexes. The cumulative function for lipophilic
      64Cu-PTSM extracted in n-octanol plateaued at levels corresponding to those
      reached by 57Co-microspheres. No consistent disagreement was found between
      cardiac output and blood flow estimated by 64Cu-PTSM and 57Co-microspheres in low
      to moderate flow tissues: muscle (0.08, 0.07 mL/min/g; 64Cu mean, 57Co mean),
      brain (0.52, 0.43 mL/min/g) and kidney (2.29, 2.45 mL/min/g). However, 64Cu-PTSM
      underestimated blood flow measured by 57Co-microspheres in myocardium (4.09, 6.55
      mL/min/g). A simple tissue trapping model may therefore be suitable for the
      derivation of blood flow estimates in low to moderate flow tissues using 62,64Cu
      PTSM, PET imaging and continuous arterial sampling with n-octanol extraction.

PMID- 7632774
TI  - 191Os/191mIr-generator for studying arterial blood flow in experimental animal
      models.
AB  - Iridium-191m (191mIr, t1/2 = 4.96 sec), an ultra-short lived tracer, has turned
      out to be suitable for gamma imaging. It can be obtained in high yields from an
      191Os/191mIr-generator with a low 191Os breakthrough. In this study the blood
      flow in the carotid and kidney arteries was studied in rabbits by radionuclide
      arteriograms. In addition, the whole body retention and biodistribution of 191Os
      was studied in rats. 191mIr was obtained from an activated carbon system, in a
      modification of the procedure described in the literature. The kidney regions
      (study I) of rabbits were imaged dynamically (5 frames/second) for up to 40
      seconds, and the investigations were repeated 4-7 times in the same animal.
      Similarly, the carotid arteries were studied (study II) and from the curves flow
      parameters were calculated. In order to study the 191Os breakthrough two groups
      of rats (n = 5) were sacrificed one day and four days after injecting five
      diagnostic doses into the tail vein (study III). In study III the Os-retention
      was highest in the kidneys and spleen, followed by the muscles and liver: 0.11
      0.12% ID/g tissues were obtained at 1 day and 0.10-0.13% ID/g at 4 days,
      respectively. These values indicate that the breakthrough values are by no means
      toxic and that investigations can be repeated immediately with a negligible
      radiation exposure. The investigations performed with the same animals (I-II)
      could be easily repeated and were reproducible. All of this indicates that 191mIr
      is suitable for radionuclide angiography and the generator system is simple and
      safe to use (191Os is beta-emitter).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7632776
TI  - Uptake of radiolabelled tyrosine and iodo-methyl tyrosine in experimental rat
      tumours: influence of blood flow and tumour growth rate.
AB  - Radiolabelled amino acids combined with Positron Emission Tomography (PET) may be
      useful for delineation of the extent of viable tumour and may also provide a
      rapid and sensitive indicator of response to therapy. Promising early clinical
      reports led us to investigate the potential use of the amino acid analogue L-3
      iodo-alpha-methyl tyrosine (IMT), which may be radioiodinated with isotopes
      suitable for PET or conventional single photon imaging. We have studied the
      biodistribution and kinetics of [125I]IMT using two transplantable tumour systems
      in hooded rats, and have compared the findings with those using the natural amino
      acid L-tyrosine (TYR) radiolabelled with tritium. Similar levels of IMT and TYR
      uptake were found in HSN and OES.HR1 tumours during tumour growth. Following
      arrest of OES.HR1 tumour growth by oestrogen ablation, reduced IMT and TYR uptake
      was found to be closely matched by a fall in tumour blood flow. Unlike IMT, a
      substantial proportion of TYR uptake in tumours was found to be protein
      incorporated, even following tumour growth arrest. Quantitative autoradiography
      revealed sharp delineation of tumour boundary using either radiotracer. We
      conclude that IMT and TYR kinetics are strongly influenced by blood flow and
      diffusion, and that tumour growth status may not be closely associated with amino
      acid uptake.

PMID- 7632777
TI  - Biodistribution and kinetics of radiolabelled pyrrolidino-4-iodo-tamoxifen:
      prospects for pharmacokinetic studies using PET.
AB  - With a view to evaluating the role of PET imaging in early clinical studies of
      new anticancer drugs, we are investigating the recently developed antiestrogen
      compound pyrrolidino-4-iodo-tamoxifen (idoxifene). Preliminary experimental
      studies have been undertaken using [125,131I]idoxifene, following synthesis of a
      tributyl-stannyl-idoxifene precursor to facilitate radioiodination. We have
      investigated the tissue biodistribution and kinetics of [125I]idoxifene following
      i.v. infusion in hooded rats bearing the hormone-dependent transplantable mammary
      tumour OES.HR1. Clearance of idoxifene from the circulation is accompanied by an
      increase in uptake by tumour and uterus, to peak levels after 24 hours (0.33 +/-
      0.037% dose/g (mean +/- 1 SD) and 0.40 +/- 0.033% dose/g, respectively). Highest
      uptake of idoxifene was found in the liver (11.0 +/- 0.8% dose/g), with a
      progressive fall after 24 hours consistent with hepatobiliary excretion of the
      radiotracer. No evidence of idoxifene metabolism was found in tissue extracts
      taken up to 48 hours. Whole body clearance of [131I]idoxifene was characterised
      by a single exponential decay (t1/2 = 140 hours) up to 350 hours post
      administration. We conclude that 124I-labelled idoxifene combined with PET
      imaging would facilitate human in vivo pharmacokinetic studies of this new
      anticancer drug and provide an opportunity to investigate relationships between
      drug uptake and tumour response.

PMID- 7632779
TI  - AIDS' impact. 2nd International Conference on Biopsychological Aspects of HIV and
      AIDS. Brighton, UK, 7-10 July 1994. Proceedings.

PMID- 7632778
TI  - 99mTc-ADP: a potential agent for in vivo tumor detection.
AB  - The possibility of using 99mTc-labelled nucleotides as tumour seeking agents has
      been proposed by different research groups. We have recently reported the
      preparation of a 99mTc-ADP complex with a high radiochemical purity (> 95%), good
      in vitro and in vivo stability and promising biodistribution results when
      injected in mice bearing spontaneous mammary adenocarcinomas. Here we report the
      results of further investigations in animals with spontaneous neoplastic
      processes, including whole-body autoradiography in mice (20 minutes and 60
      minutes post injection) and gamma-camera imaging studies in Wistar rats. Dynamic
      studies (up to 45 minutes) and static images (up to 18 hours) were acquired to
      determine the pharmacokinetics of 99mTc-ADP and the tumour/muscle and
      tumour/blood ratios. Blood-pool studies were also performed as a control. Tumours
      were visualized by autoradiography as was to be expected from the biodistribution
      studies. Dynamic studies showed a rapid blood clearance and a behaviour that
      fitted to a tricompartimental model. Radioactivity was rapidly taken up by the
      kidneys and excreted in the urine. No evidence of in vivo instability of the
      complex was observed. Tumour uptake reached the maximum values after 20 minutes
      post-injection. Tumour/blood and tumour/muscle ratios improved over time,
      enhancing tumour visualization. The best images were obtained after 3 hours post
      injection. In summary, our studies suggest that 99mTc-ADP is a promising
      radiopharmaceutical for tumour diagnosis.

PMID- 7632780
TI  - Why we need to rethink AIDS education for gay men.
AB  - This paper examines critically the issue of prevention of HIV infection for gay
      men. Evidence for the persistence of unsafe sexual behaviour in gay men is
      provided, followed by discussion of obstacles to the development of effective
      interventions to initiate and maintain safer sex behaviour.

PMID- 7632781
TI  - Reaching male clients of female prostitutes: the challenge for HIV prevention.
AB  - Male clients of prostitutes have proved to be a very difficult group to access
      for the purposes of HIV research and education. Prevention initiatives to date
      have placed less emphasis on HIV awareness with this potential target group and
      more on empowering prostitutes to control the sexual transaction with clients.
      Data is presented from a study of male clients of prostitutes, conducted as part
      of a wider study of drug using and nondrug using prostitutes in the Greater
      Manchester area during 1991-92. The study focuses on sexual activities and risk
      behaviours of male clients with female prostitutes, and with regular and casual
      partners. The data provides evidence of high levels of risk-taking, particularly
      by bisexual clients. Implications for research and HIV prevention are discussed.
      It is concluded that placing the major burden for behaviour change on prostitutes
      themselves may have only a limited effect and that other involved persons
      (including clients) should be more actively targeted in the development and
      implementation of STD/HIV prevention.

PMID- 7632782
TI  - Gender differences in HIV-related psychological distress in heterosexual couples.
AB  - In order to determine the effect of family support on the psychological well
      being of heterosexual couples with at least one HIV-seropositive, family support
      data were obtained from couples, who were separately interviewed. Two hundred
      heterosexuals were interviewed (97 males, 103 females). 182 were partners in HIV
      serodiscordant couples (18 members were in 10 couples concordant for HIV
      seropositivity). Overall, there were 76 HIV+ males and 30 HIV+ females. The Brief
      Symptom Inventory (BSI) was used to measure psychological distress. Sixty-five
      per cent of the subjects had family members aware of partners' HIV infection, but
      only 50% of aware families were reported as supportive. Family support was not a
      significant predictor of distress. Gender was the most significant predictor of
      psychological distress as measured by the BSI subscales. Both HIV positive and
      HIV negative females had more distress than their male counterparts on several
      dimensions (somatization, obsessive-compulsive, interpersonal sensitivity,
      depression, anxiety, phobic anxiety and paranoia), and on the General Severity
      Index (GSI) of the BSI (HIV-positives: p = 0.003; HIV-negatives: p = 0.01).
      Despite the general lack of association of family support with psychological
      distress, women in couples affected by HIV had more distress than men. The mental
      health needs of women clearly differ from men, and continued gender comparisons
      should be done to develop appropriate and effective interventions for these
      groups.

PMID- 7632783
TI  - Differences in HIV testing, knowledge and attitudes in pregnant women who deliver
      and those who terminate: Prevagest 1992--France.
AB  - The object of this study supported by the French Agency for AIDs Research (ANRS)
      was to assess knowledge and attitudes of pregnant women towards HIV infection and
      testing, and to compare them according to the outcome of the pregnancy (elective
      abortion vs delivery). Between March 22 and April 26, 1992, all women ending
      their pregnancy and attending one of the 72 medical centres located in South
      Eastern France were asked to complete an anonymous questionnaire (n = 4303).
      3,854 (89.6%) responded: 2,825 women at delivery (WD) and 764 who chose an
      elective abortion (WA). 61.7% of WD and 24.1% of WA declared having been tested
      for HIV during pregnancy (p < 0.001). Among women who reported not having been
      HIV tested, very few did so because they refused the test (1.7% among WD and 1.4%
      among WA-NS). Prior HIV testing was less frequent among WA than among WD (45.8%
      vs 58.8%--p < 0.001). 2.8% of women tested during prenatal care and 20% in the
      context of abortion did not know the result of their test (p < 0.001). Knowledge
      about HIV transmission declared by WD did not differ significantly from that
      declared by WA. However, risky behaviours were more frequent among WA than among
      WD (38.9% vs 17.7%--p < 0.001). This research shows that French screening HIV
      policy in the context of pregnancy remains mainly motivated by foetal concerns.
      Although women who abort voluntarily report risky behaviours more frequently, the
      opportunity of information and counselling towards them is relatively neglected
      in comparison with women who deliver.

PMID- 7632784
TI  - 'Life' for a non-progressor.
AB  - A "non-progressor" with HIV, diagnosed in 1984, comments from a personal
      perspective on how people with HIV are affected by social and professional
      attitudes. The failure of some professionals to develop an understanding of HIV
      beyond their own particular field of expertise contributes to the disempowerment
      experienced by those infected and can result in broader social and and
      psychosocial aspects of HIV, such as discrimination, being inadequately
      addressed.

PMID- 7632785
TI  - Orphans of the HIV epidemic: unmet needs in six US cities.
AB  - In the United States, an estimated 72,000-125,000 children and adolescents will
      lose their mothers to AIDS by the year 2000. Six cities have been particularly
      hard hit: New York City, Newark, Miami, San Juan, Los Angeles, and Washington,
      DC. The most urgent unmet needs for children, their families and new guardians
      are for mental health services, including bereavement counselling; transitional
      services to help overcome the loss of AIDS-related benefits following the
      parent's death; legal services; housing supports, and appropriate evaluations and
      referrals by juvenile justice and school staff to community-based services.
      Professional staff need additional training and support. Public policies and
      legal standards should stress a preference for maintaining children in their
      extended families, broadly defined, whenever possible. Much more needs to be done
      to improve the lives and futures of these youth.

PMID- 7632786
TI  - Caring for people with AIDS in a Nigerian teaching hospital: staff attitudes and
      knowledge.
AB  - Health workers (HWs) play a pivotal role in preventative programmes being
      implemented to combat the steady increase in the prevalence of HIV infection and
      AIDS in Nigeria. We report on a questionnaire survey conducted in October, 1993
      among 111 doctors, 92 nurses and 53 non-health workers at the University of
      Ilorin Teaching Hospital, Ilorin, Nigeria. The aim was to assess their knowledge
      of AIDS (for all groups) and the attitude of the HWs only towards the care of
      patients with AIDS (PWAs). Although important gaps in knowledge were found in all
      groups, doctors performed significantly better than non-health workers on 22 out
      of 23 knowledge items, and more than nurses on 8 of such items. Nurses scored
      significantly higher than non-health workers on 18 of the knowledge items and
      more than doctors on one knowledge item. About one in three nurses would hesitate
      to nurse a PWA, while half would not participate in birth delivery. Also, about a
      quarter of doctors would hesitate to treat a PWA while one in three would not
      carry out surgery despite adequate precautions. The findings compare favourably
      with those reported from other countries. However, they still indicate the need
      for a comprehensive AIDS education package to improve the knowledge base and
      allay fears for all groups and to prepare HWs for the important task of caring
      for PWAs.

PMID- 7632787
TI  - Analysis of psychiatric consultations in patients with HIV infection and related
      syndromes.
AB  - Patients referred to the consultation-liaison psychiatry department of the
      University of Ferrara over a 12 month period were studied. About 13% of referrals
      concerned HIV patients. Comparison of HIV infected with non-HIV infected
      referrals revealed differences in the reasons for psychiatric consultation and
      the diagnosis made after assessment, as well as in the number of follow-up
      consultations. The implications of the findings are discussed.

PMID- 7632788
TI  - Commitment, value conflicts and role strains among French GPs in care for HIV
      positive patients.
AB  - A survey was carried out on a random sample of GPs in the city of Marseille.
      18.5% had been involved during the past year in a regular follow-up of HIV
      patients. They were in charge with 79.8% of all ambulatory care of HIV+ patients.
      Those informally 'specialized' professionals were connected to health networks
      (not only hospital structures but also associations dealing with commitment in
      care). Socio-biographical factors, training and environmental opportunities and
      ideological orientations would positively relate with commitment in care. GPs who
      were not involved with care, would worry more about personal risk of
      contamination; would not believe that wearing gloves could be a sufficient
      protection when doing invasive procedures; would feel less at ease with HIV
      patients, would be more strongly in favor of coercive measures with IVDU's. Most
      GP's would agree to avoid drug users HIV+ patients. They would attribute to them
      more guilt and responsibility than to other patients. Uncertainty concerning
      relevant knowledge, negative attitudes towards some patients like IVDU's and
      anticipated difficulties to deal with ethical and relational dilemmas keep
      limiting GPs interest and positive motivation in care for HIV patients.

PMID- 7632789
TI  - Relationship between safe sex and acculturation into the gay subculture.
AB  - There is some evidence, although conflicting, to suggest that socialization or
      acculturation into the gay community is associated with lower levels of unsafe
      sex. We attempted to determine the relationship between acculturation and sexual
      safety. We examined data from 282 men (from the Dallas AIDS Community
      Demonstration Project) who had sex with men and were not in a monogamous
      relationship to determine the associations between safer sex and indices of
      acculturation. The indices of acculturation included regular reading of local and
      national gay newspapers and magazines, and belonging to an organization for gay
      men. The data indicated that there were significant relationships between
      acculturation, talking to sexual partners about HIV risk reduction and sexual
      identity, and the dependent variable of frequency of condom use for anal sex. A
      regression equation indicated that 21% of the variance of anal condom use was
      predicted by these variables. These data suggest that acculturation into the gay
      community is associated with safer sexual behaviour, and we discuss the
      implications of these data for using role models and normative beliefs in HIV
      prevention programmes.

PMID- 7632790
TI  - Risk behaviours of inmates in south-eastern France.
AB  - This study was set up to compare risk behaviours between IDU and no-IDU inmates
      and among IDUs and to elicit the differences of preventive and risk behaviours
      according to sex. It was carried out in the Baumettes Prison, France, from
      November 16 to December 21, 1992; 295 male and 137 female inmates were
      interviewed using a self-questionnaire checked by the medical staff. Twenty per
      cent of participants (85/432) declared to be IDU (heroin); half of them reported
      needle sharing. After adjustment for age and sex, the number of sexual partners
      during the last year was significantly higher among IDU inmates (more than two
      partners: 19% vs 9.5%); similarly, sexual intercourse with an IDU during the last
      five years was reported more frequently by IDUs (47% vs 5%). After adjustment for
      the number of sexual partners, the proportion of IDUs who declared using always
      condoms was higher than that of non-IDUs (30.5% vs 13%). IDUs reported a prior
      HIV testing more often than no-IDUs (93% vs 49%). Multidimensional analysis
      showed that IDU female inmates reported having been HIV tested (100% vs 88%), had
      sexual intercourse with an IDU (73.5% vs 25.5%) and practised needle sharing (62%
      vs 43%) more often than male IDU inmates. This survey shows that, beyond drug
      taking which is the main risk factor for HIV infection in the carceral
      population, sexual behaviours could be an additional risk factor among IDU
      inmates, especially among women.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7632791
TI  - Health care personnel's critique on the Philippines' first movie on AIDS.
AB  - The "Dolzura Cortez Story" was the Philippines' first movie on AIDS that provided
      'a name and a face' among the 50 recorded lives that were lost to AIDS in 1992.
      This movie was utilized as a focus of discussion by some health care personnel to
      express their thoughts, opinions and recommendations regarding the use of cinema
      as a powerful tool for AIDS information dissemination.

PMID- 7632792
TI  - An assessment of self-esteem in HIV-positive patients.
AB  - The objective of this research is to assess how self-esteem levels differ in HIV
      infected subjects in three different risk behaviours: drug addicts, homosexuals,
      heterosexuals. The sample (n = 104) consisted of: drug addicts (n = 46);
      homosexual (n = 26); heterosexuals (n = 32). The Rosenberg Self-Esteem Scale
      (RSES) and the Eysenck Personality Inventory (EPI) were used. A covariance
      analysis was used to assess the effect of the different personality traits on the
      'self-esteem variable' and to eliminate the variance caused by the personality
      variables. Bonferroni's T-test was used to assess which group contributed to
      confute the hypothesis of equivalence between the RSES means of the groups. A
      significant association between the HIV-infection risk behaviour and the level of
      self-esteem was shown; this association was assessed by eliminating the effect of
      personality traits. The risk behaviour as well as the personality traits were
      both indicative of the level of self-esteem. The assessment of each group
      revealed that the drug addicts had a relatively lower self-esteem level (mean =
      35.251) than the homosexuals (mean = 38.698) and the heterosexuals (mean =
      38.227). In conclusion the RSES enables clinicians to identify subjects with low
      levels of self-esteem who need to be psychologically assessed within a vast
      population of HIV-infected patients.

PMID- 7632793
TI  - Syntheses and properties of luminescent lanthanide chelate labels and labeled
      haptenic antigens for homogeneous immunoassays.
AB  - Lanthanide chelate labels containing substituted 4-(arylethynyl)pyridine as the
      chromogenic moiety and iminobis(acetic acid) groups as the chelating part were
      synthesized. N-Succinimidyl esters of the carboxy derivatives of thyroxine and
      progesterone were prepared and coupled to the aliphatic amino groups of the
      synthesized lanthanide chelates. The luminescence properties of the chelates and
      labeled haptenic antigens were measured in ethanol and in an aqueous buffer
      containing either albumin or detergents as luminescence-modulating compounds. The
      energy transfer enhanced ion luminescence of the derivatives containing a para
      amino-substituted phenyl ring showed particularly strong dependence on
      environmental changes, which makes these derivatives well suited for homogeneous
      time-resolved fluoroimmunoassay based on the use of external luminescence
      modulators.

PMID- 7632795
TI  - Synthesis and characterization of superoxide dismutase-deferoxamine conjugate via
      polyoxyethylene: a new molecular device for removal of a variety of reactive
      oxygen species.
AB  - A conjugate of Cu,Zn-superoxide dismutase (SOD) with a strong iron chelating
      agent, deferoxamine (DFO), was synthesized (SOD-POE-DFO) via polyoxyethylene
      (POE) as a linking agent. N-terminal amino groups of lysine residues in SOD are
      modified with 1:1 binding products of polyoxyethylene and deferoxamine (POE-DFO)
      through a covalent amido bond. The mean number of the POE-DFO bound per one SOD
      molecule is calculated to be 3.3 by determining the C/N ratio after elemental
      analysis. The half-life of the SOD-POE-DFO is about 1.2 h in rats, whereas that
      of free SOD is about 5-10 min. POE plays the part not only of the linking agent
      but also of expanding the lifetime in the circulation. The SOD-POE-DFO possesses
      both the metal chelating ability (for DFO) and the ability of scavenging
      superoxide radicals (for SOD). Therefore, the SOD-POE-DFO of the present study
      can eliminate the superoxide radical and free iron simultaneously and in the same
      location, and thus, it would be a molecular device with multiple functions which
      prevents the damage to tissues by scavenging the variety of reactive oxygen
      species.

PMID- 7632794
TI  - Synthesis and applications of a new poly(ethylene glycol) derivative for the
      crosslinking of amines with thiols.
AB  - A heterobifunctional crosslinker was synthesized from a diamine derivative of
      poly(ethylene glycol) (PEG, average molecular weight 800 Da), with the functional
      groups 2-(pyridyldithio)propionyl (PDP) and N-hydroxysuccinimide ester (NHS). The
      crosslinker can be used for linkage of two different proteins for which a
      suitable protocol is presented, explified by crosslinking of two antibodies with
      50% yield. In a second application the crosslinker is used to generate
      immunoliposomes. The NHS group was reacted with an aminolipid for liposome
      anchorage, and antibodies were bound to the PDP group via disulfide bonds.
      Loading of liposomes with antibodies was easily adjustable, even down to only a
      few per liposome. This crosslinker with its particular length appears especially
      suited for the flexible anchorage of biomembranes, opening new perspectives in
      membrane research as discussed.

PMID- 7632796
TI  - "Cleavable trifunctional" approach to receptor affinity labeling: chemical
      regeneration of binding to A1-adenosine receptors.
AB  - A general approach for reversible affinity labeling of receptors has been
      developed. The objective is to carry out a series of chemical modifications
      resulting in a covalently-modified, yet functionally-regenerated, receptor
      protein that also may contain a reporter group. The ligand recognition site of A1
      adenosine receptors in bovine brain membranes was probed to demonstrated the
      feasibility of this approach. Use of disulfide or ester linkages, intended for
      cleavage by exposure of the labeled receptor to either reducing reagents or
      hydroxylamine, respectively, was considered. Binding of the antagonist
      radioligand [3H]CPX was preserved following incubation of the native receptor
      with 3 M hydroxylamine, while binding was inhibited by the reducing reagent
      dithiothreitol (DTT) with an IC50 of 0.29 M. Hydroxylamine displaced specific
      agonist ([3H]PIA) binding in a noncovalent manner. Specific affinity labels
      containing reactive isothiocyanate groups were synthesized from XCC (8-[4
      ](carboxymethyl)-oxy]phenyl]-1,3-dipropylxanthine) and shown to bind irreversibly
      to A1-receptors. The ligands were structurally similar to previously reported
      xanthine inhibitors (e.g., DITC-XAC: (1989) J. Med. Chem. 32, 1043) except that
      either a disulfide linkage or an ester linkage was incorporated in the chain
      between the pharmacophore and the isothiocyanate-substituted ring. These groups
      were intended for chemical cleavage by thiols or hydroxylamine, respectively.
      Radioligand binding to A1-receptors was inhibited by these reactive xanthines in
      a manner that was not reversed by repeated washing. Hydroxylamine or DTT restored
      a significant fraction of the binding of [3H]CPX in A1-receptors inhibited by the
      appropriate cleavable xanthine isothiocyanate derivative.

PMID- 7632797
TI  - Calcium responsive two-dimensional molecular assembling of lipid-conjugated
      calmodulin.
AB  - Calmodulin (CaM), a calcium ion sensitive protein, was conjugated with
      dioctadecyldimethylammonium bromide and subsequently assembled into a monolayer
      at the air-water interface using the LB method. The lipid-conjugated calmodulin
      (LCC) retains its calcium sensitivity, determined from the changes in the area
      pressure isotherm of the monolayer obtained at the air-water interface. The
      functionality of this protein assembly was characterized by the activation of
      phosphodiesterase (PDE), a CaM responsive enzyme. The enzyme activity of PDE
      coupled with LCC at the air-water interface was measured by using the enzymatic
      method. It was found that LCC retained its enzyme activity modulating function of
      calmodulin, which is triggered by calcium ions. This characteristic plays an
      important role in fabricating molecular assembly of proteins which have a
      cooperative interaction at the molecular level.

PMID- 7632798
TI  - Synthesis and use of a new bromoacetyl-derivatized heterotrifunctional amino acid
      for conjugation of cyclic RGD-containing peptides derived from human bone
      sialoprotein.
AB  - A new amino acid derivative, N alpha-(tert-butyloxycarbonyl)-N beta
      (bromoacetyl)diaminopropionic acid (BBDap), has been synthesized as a reagent for
      introducing side-chain bromaocetyl groups into any position of a peptide sequence
      during solid-phase peptide synthesis. By using minor modifications to the
      protocol of the automated peptide synthesizer and a two-step in situ
      neutralization procedure, the syntheses of (bromoacetyl)diaminopropionic acid
      (BDap) in Arg-Gly-Asp-containing peptides from human bone sialoprotein were
      optimized and completed. Following HPLC purification, the BDap-derivatized
      peptides were cyclized or/and conjugated to carrier protein or to glass cover
      slips. In addition, a new procedure for site-specific conjugation of cyclic
      peptides to protein carriers or to glass was developed. The cell attachment
      activity of the peptide derivatives and conjugates was tested in cell adhesion
      assays with human osteoblasts, and the specificity of the binding was confirmed
      by competition with linear and/or cyclic forms of GRGDS. The results show that
      conjugates containing the linear and cyclic derivatives of the peptide EPRGDNYR
      supported cell attachment and spreading in a dose-dependent manner when the
      peptides were immobilized as described. Cell attachment to the intact bone
      sialoprotein and to conjugates containing the linear peptides was abolished by
      competition with linear and cyclic RGD-containing peptides, whereas the
      attachment to conjugates containing the cyclic peptide was inhibited only
      partially, and the cell spreading was preserved even in the presence of RGD
      peptides.

PMID- 7632800
TI  - Targeted gene delivery with a low molecular weight glycopeptide carrier.
AB  - A low molecular weight glycopeptide carrier was prepared by coupling a
      tyrosinamide-triantennary oligosaccharide to dp19 poly-L-lysine resulting in a
      1:1 conjugate. The glycopeptide carrier complexed with plasmid DNA as evidenced
      by displacement of intercalated dye, light scattering by condensed DNA, and
      immobility of complexed DNA upon agarose gel electrophoresis. DNA-carrier
      complexes were endocytosed into HepG2 cells via the asialoglycoprotein receptor
      due to recognition of terminal galactose residues on the oligosaccharide. The
      resulting luciferase reporter gene expression was dramatically influenced by the
      solubility of complexes, the extent of complexation, and the presence of the
      lysosomotropic agent chloroquine. The results suggest that low molecular weight
      glycopeptides may be suitable for further development as well-defined DNA
      carriers for receptor-mediated gene delivery in vivo.

PMID- 7632799
TI  - Selective binding of pyrido[2,3-d]pyrimidine 2'-deoxyribonucleoside to AT base
      pairs in antiparallel triple helices.
AB  - Triple helix-forming oligonucleotides (TFOs) offer the potential to specifically
      modulate expression of gene in a sequence dependent manner. TFOs containing G and
      T residues that bind to duplex DNA, forming a series of GGC and TAT base
      triplets, have been well studied. It has been observed that T is relatively
      nonspecific in that it binds with similar affinity to AT, GC, and CG base pairs.
      This may significantly reduce the specificity of a given TFO, leading to
      undesired effects on the expression of genes unrelated to the intended target. We
      have now prepared 3-(2-deoxy-beta-D-erythro-pentofuranosyl)-pyrido[2,3
      d]pyrimidine-2,7(8H )- dione (P) and incorporated it into TFOs using the solid
      support, phosphoramidite chemistry. It has been demonstrated that a limited
      substitution of P for T in a G-rich 26-mer TFO can improve binding specificity
      for AT base pairs in antiparallel motif under certain conditions. The specificity
      exhibited by P is suggestive of base pair specific interactions that influence
      the binding strength and consequently enhance the potential therapeutic
      application of TFOs. However, the effect of substitution of P for T is dependent
      on the binding conditions, as well as the number of position of substitutions.

PMID- 7632801
TI  - Dual-specificity interaction of HIV-1 TAR RNA with Tat peptide-oligonucleotide
      conjugates.
AB  - An oligonucleotide-peptide conjugate, having dual binding capability for a
      designated RNA, was designed. The peptide portion of the conjugate interacts with
      a folded domain in the RNA, whereas the oligonucleotide portion hybridizes with a
      nearby single-stranded region in the RNA. The dual specificity was proven in a
      model HIV-1 TAR RNA system using an RNase H cleavage assay to assess antisense
      binding to this RNA. The peptide portion of the conjugate was shown to confer
      increased specificity on the oligonucleotide.

PMID- 7632805
TI  - Strategies for the synthesis and screening of glycoconjugates. 1. A library of
      glycosylamines.
AB  - A simple one-step procedure is found to be highly effective for the
      "functionalization" of glycodiversity. This study encompasses 50 unprotected mono
      and oligosaccharides, which are subjected to Kochetkov aminations in saturated
      aqueous ammonium carbonate. The reaction allows for the stereo- and
      regioselective introduction of an amino group into all oligosaccharides tested,
      as well as into a great variety of monosaccharides including charged species. The
      resulting unprotected glycosylamines are stable compounds, and the inherent amino
      group provides a convenient site for chemoselective conjugation and modification
      as described in the following paper in this issue.

PMID- 7632803
TI  - Construction of coordinatively saturated rhodium complexes containing appended
      peptides.
AB  - Phenanthrenequinone diimine (phi) complexes of rhodium(III) bearing appended
      peptides have been prepared using two complementary solid phase synthetic
      strategies. The first method involves the direct coupling of the coordinatively
      saturated rhodium complex containing a pendant carboxylate to the N-terminus of a
      resin-bound peptide, in a manner analogous to the chain-elongation step in solid
      phase peptide synthesis. The second involves coupling a bidentate chelator
      containing the pendant carboxylate to the resin-bound peptide, followed by
      coordination of [Rh(phi)2]3+ to the bidentate chelator attached to the peptide.
      Peptides of length 5-30 residues have been covalently attached to rhodium
      complexes in 5-18% yield using both methods. Despite the low overall yields, the
      regioselective modification of the peptide chain afforded by these strategies is
      a distinct advantage over solution phase methods. With coordination complexes
      which are stable to peptide deprotection and cleavage conditions from the resin,
      the solid phase synthetic strategies are convenient to apply. Amino acid
      analysis, electronic spectroscopy, and circular dichroism confirm the presence of
      the two components in the metal-peptide chimeras; the metal-peptide complexes
      exhibit the combined spectral properties of the parent metal complex and the
      appended peptide. Significantly, plasma desorption mass spectrometry reveals a
      novel pattern of peptide fragmentation for the metal-peptide chimeras that is not
      observed in the absence of the tethered metal complex; this fragmentation
      facilitates the sequence analysis of the appended peptide. Thus, metal-peptide
      chimeras may be conveniently prepared using solid phase methodologies, and
      features of coordination chemistry may be exploited for new peptide design and
      analysis.

PMID- 7632802
TI  - Improved synthesis of 6-[p-(bromoacetamido)benzyl]-1,4,8,11
      tetraazacyclotetradecane- N,N',N",N"-tetraacetic acid and development of a thin
      layer assay for thiol-reactive bifunctional chelating agents.
AB  - Monoclonal antibodies labeled with radiometals such as copper-67 have
      applications in radioimmunodiagnosis and radioimmunotherapy. Moi et al. [(1985)
      Anal. Biochem. 148, 249-253] showed that 6-[p-(bromoacetamido)benzyl]-1,4,8,11
      tetraazacyclotetradecane- N,N',N",N"-tetraacetic acid (BAT) is an effective
      reagent for linking copper to proteins, and antibodies labeled with copper
      radionuclides are currently undergoing clinical trials. Here we describe
      improvements in the original synthesis that increase the overall yield of BAT to
      23%. We also describe a new assay useful to determine the activity of
      bifunctional chelating agents with thiol-reactive functional groups.

PMID- 7632804
TI  - Electrophoretic method for the quantitative determination of a benzyl-DTPA ligand
      in DTPA monoclonal antibody conjugates.
AB  - A simple electrophoretic IEF procedure was developed for the quantitation of
      bifunctional DTPA ligand molecules in DTPA-protein conjugates. From a calibration
      plot of pI versus substitution ratios of reference conjugates, the concentrations
      of DTPA conjugated to protein were determined. Molar ratios of DTPA to protein
      agreed satisfactorily with the ratios obtained by a spectrophotometric technique
      using a colored yttrium(III) complex of arsenazo III. The IEF method was
      successfully applied on preparations of benzyl-DTPA to mAbs MOPC-21, SC-20
      (aCEA), and human serum albumin.

PMID- 7632806
TI  - Strategies for the synthesis and screening of glycoconjugates. 2. Covalent
      immobilization for flow cytometry.
AB  - Glycosylamines are readily available carbohydrate derivatives that undergo
      acylation reactions with homobifunctional N-hydroxysuccinimidyl esters. The
      product glycosylamides carry a spacer group equipped with one active ester
      functionality. This route provides well-defined glycoconjugates, which may be
      cross-linked to various amino-functionalized resins. Carbohydrate recognition of
      the resulting sugar-bead conjugates is probed by lectin immunostaining or flow
      cytometry using a fluorescently labeled lectin.

PMID- 7632807
TI  - A convenient route to thiol terminated peptides for conjugation and surface
      functionalization strategies.
AB  - The derivatization of poly(p-(chloromethyl)styrene-co-divinylbenzene) (Merrifield
      resin) with N-(tert-butoxycarbonyl)-2-aminoethanethiol is presented as a
      convenient route for the generation of thiol terminated peptides using a solid
      phase methodology. Maximum resin substitution reached 92% (773 mumol/g) after 24
      h. However, at 30 min, yields exceeded 400 mumol/g, above which the resin is
      suitable for solid phase peptide synthesis. Thiol terminated peptides are well
      suited for subsequent chemical conjugation reactions or for the formation of
      organic monolayers on metal substrates.

PMID- 7632808
TI  - AML-MO: clinical entity or waste basket for immature blastic leukemias? A
      description of 14 patients. Dutch Slide Review Committee of Leukemias in Adults.
AB  - In the period from August 1991 to August 1994, the Dutch Slide Review Committee
      of Adult Leukemias classified 14 leukemias as AML-M0. We reviewed the clinical
      characteristics and response to therapy of these patients. Eight patients were
      male. Patients' age ranged from 7 to 77 years (medium age 62 years). There was a
      striking homogeneity in morphological appearance of the blasts, being small to
      medium-sized round cells with often an eccentric nucleus with fine chromatin,
      several distinct nucleoli, and a high nucleo-cytoplasmic ratio. In addition to
      myeloid-associated markers such as CD13 and CD33, the blasts of all patients were
      positive for CD34 and HLA-DR, pointing to their immature differentiation stage.
      TdT was present in the blasts of 71%, CD7 was positive in the blasts of 42% of
      the patients. No consistent cytogenetic abnormalities were found. With respect to
      the treatment outcome, four patients achieved a complete remission after
      remission-induction treatment. The median survival was 4.5 months. Our present
      study shows AML-M0 to be an immature leukemia, uniform in morphology and
      immunological phenotype, with no consistent cytogenetic phenotype and with a poor
      clinical outcome.

PMID- 7632809
TI  - Comparison of scoring systems in primary myelodysplastic syndromes.
AB  - To compare the prognostic value of scoring systems in primary myelodysplastic
      syndromes (pMDS), four clinicohematological systems (Rennes, Bournemouth,
      Dusseldorf, Pavia) and the histopathological Hannover Scoring System were applied
      to 415 MDS patients from the Bone Marrow Registry of Hannover Medical School.
      According to the FAB classification, 180 patients (43%) were diagnosed as RA, 33
      (8%) as RARS, 99 (24%) as RAEB, 36 (9%) as RAEBt, and 48 (12%) as CMMOL; 19
      patients (4%) were not further classified (MDS.UC). All scoring systems revealed
      three or four groups of patients with significantly different survival times. The
      ranges and standard deviations in these groups were similar but high in all
      scoring systems. A good differentiation between short-term survivors (< 1 year
      survival time) and intermediate-term survivors (1-4 years) was possible with all
      tested scoring systems, but the differentiation between intermediate- and long
      term survivors (> 4 years) was not distinctive enough. The problem of risk
      assessment in the single patient is furthermore elucidated by the values of
      specificity and sensitivity, which were relatively low in all scoring systems
      tested. Best results were yielded by the Bournemouth Score for long-term
      survivors and the Dusseldorf and Hannover Score for intermediate- and short-term
      survivors. Multivariate analysis of all parameters used in the scoring systems
      showed the highest negative impact on survival for increase of myeloblasts,
      anemia, myelofibrosis, high age of the patient, and abnormal localization of
      immature precursors (ALIPs). Therefore, the histopathological Hannover Scoring
      System is not only equal to clinicohematological risk assessment in pMDS, but
      also includes important independent prognostic parameters. Risk assessment for
      the individual low-risk MDS patient using only initial parameters may be rendered
      impossible due to the biological nature of pMDS. Therefore, sequential analysis
      is needed to elucidate random events which alter the prognosis.

PMID- 7632810
TI  - Interleukin-6 (IL-6) levels in febrile children during maximal aplasia after bone
      marrow transplantation (BMT) are similar to those in children with normal
      hematopoiesis.
AB  - Interleukin-6 (IL-6) has been shown to be an inducer of the acute-phase response
      (APR) and to be involved in the pathogenesis of several disease states, including
      graft-versus-host disease (GvHD) following allogeneic bone marrow transplantation
      (BMT). As blood cells of the monocyte lineage are known to be major producers of
      this cytokine, we wondered whether extreme peripheral leukopenia following total
      ablation of hematopoiesis could compromise IL-6 production during the first days
      after allogeneic or autologous BMT. In the absence of detectable circulating
      leukocytes we measured elevated IL-6 levels in six children having fever (> or =
      38 degrees C) of presumed infectious origin with an average of 74 +/- 60 units/ml
      (range 19-309 units/ml). IL-6 levels in febrile children having a normal
      hematopoiesis (118 +/- 254 units/ml, range 17-1213 units/ml) were not
      significantly higher than those found in the febrile BMT group (p > 0.05).
      Moreover, there was a clear association between elevated IL-6 levels and the
      presence of fever. C-reactive protein (CRP) was also elevated (> or = 1 mg/dl),
      whereas tumor-necrosis factor alpha (TNF) was undetectable (< 1 pg/ml). Two
      transplanted patients without fever during the period of total aplasia had
      neither detectable CRP nor IL-6, thus demonstrating that the transplant procedure
      itself does not induce an APR. Our data obtained during maximal leukopenia
      following BMT show that a functional hematopoietic system is not necessary for
      regular production of IL-6, which is associated with fever. Cells of
      nonhematopoietic origin may contribute to this production.

PMID- 7632811
TI  - Long-term therapy with recombinant human erythropoietin (rHu-EPO) in progressing
      multiple myeloma.
AB  - Recombinant human erythropoietin (rHu-EPO) is an effective growth factor for
      erythroid progenitor cells in anemia provoked by several conditions, including
      bone marrow tumors such as multiple myeloma (MM). We studied a group of 54
      patients with MM undergoing second-induction chemotherapy. Thirty of them were
      randomly assigned to receive rHu-EPO at an initial dosage of 150 units/kg body
      weight three times a week, increased to 300 units/kg from the sixth week to the
      end of the 24-week study. Hemoglobin (Hb) levels increased in 77.7% of these
      patients by the eighth week. In addition, five transfusion-dependent patients in
      treatment with the VMCP protocol completed the trial without requiring blood
      supplement after the third month, whereas seven control patients required
      frequent supplements. Monthly assessment of hematologic parameters demonstrated
      the ability of rHu-EPO to increase reticulocyte counts, whereas five patients
      became resistant to the second-induction chemotherapy in apparent concurrence
      with their rHu-EPO therapy. The response to rHu-EPO in four of the five MM
      patients receiving cytotoxic protocols combined with alpha-interferon (alpha-IFN)
      included an increase of serum IgM after the third month. This effect was not
      demonstrable in any other group, including three rHu-EPO-untreated patients
      undergoing alpha-IFN + VMCP combined therapy, as well as rHu-EPO-treated patients
      not receiving alpha-IFN. Our data suggest that alpha-IFN plus rHu-EPO treatment
      in MM patients is effective in restoring normal B cell function. These results
      may reflect in vivo the modulation of normal human B cells and lymphoblasts by
      rHu-EPO observed in vitro.

PMID- 7632813
TI  - A 37-year-old man with cholestatic jaundice and a prior history of Hodgkin's
      disease.

PMID- 7632812
TI  - Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome: a multivariate
      analysis of factors predicting the response to plasma exchange.
AB  - The aim of this study was to investigate pretreatment prognostic factors that
      could be useful in predicting the response to plasma exchange in thrombotic
      thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS). Thirty-two patients
      with TTP/HUS, treated with plasma exchange at our institution from 1980 to 1994,
      were studied. The main clinical and laboratory data at the beginning of plasma
      exchanges were analyzed by the Cox stepwise logistic regression, applied to
      either treatment failure or death. Seventeen (53%) patients attained a complete
      remission and 22 (69%) survived (five in advanced renal failure and long-term
      hemodialysis). Longer delay in initiating plasma exchanges, presence of stupor or
      coma, and higher creatinine levels at the beginning of plasma exchanges were
      independent predictors of treatment failure. Stupor or coma at the beginning of
      plasma exchanges was the only predictor of mortality from unremitted TTP/HUS.
      Hemoglobin levels, platelet count, and LDH activity, traditionally envisaged as
      markers of disease activity, neither correlated with previous duration of TTP/HUS
      nor had any prognostic value. Early diagnosis of TTP/HUS and prompt initiation of
      intensive plasma exchange emerged from this study as the most effective
      interventions for improving the prognosis of TTP/HUS patients.

PMID- 7632815
TI  - An update on peripheral blood progenitor cell transplantation.
AB  - High-dose therapy with stem cell rescue is increasingly being used as a salvage
      or consolidation therapy for patients with poor-risk malignant disease. The
      availability of peripheral blood progenitor cells (PBPC) has opened new
      therapeutic perspectives to alleviate the severe toxicity related to prolonged
      myelo-suppression. The preferred method of collection is still a matter of much
      debate. PBPC can be collected in steady state and after chemotherapeutic
      conditioning, growth factor priming, or both. Usually a heterogeneous population
      containing both committed progenitors and pluripotent stem cells can be
      harvested. Studies comparing engraftment after mobilized PBPC with recovery after
      autologous bone marrow transplantation confirm the beneficial effect on
      neutrophil and platelet engraftment. The accelerated hematological recovery can
      be associated with a number of clinical benefits including a reduction of
      platelet transfusions and shorter hospital stay. Only a few randomized studies
      are currently available on the long-term outcome after PBPC transplantation.
      Recent findings on tumor cell mobilization stimulated the development of
      techniques for tumor cell reduction, based on negative selection ("purging") of
      tumor cells or positive selection of CD34-positive progenitor cells. Positive
      CD34 selection is also imperative for successful ex vivo expansion of progenitor
      cells and gene transfer experiments. The value of PBPC in the field of allogeneic
      transplantation is currently being examined.

PMID- 7632816
TI  - FAB classification of myelodysplastic syndromes: merits and controversies.
AB  - Guidelines for the definition and diagnosis of myelodysplasia were set out by the
      French-American-British Cooperative group (FAB), and the resulting framework has
      greatly helped the now very large number of workers in many scientific
      disciplines who are actively investigating the myelodysplastic syndromes (MDS).
      Most patients with MDS can be readily classified into clinically relevant
      subgroups by correlation of clinical findings with the findings from well
      prepared peripheral blood and bone marrow specimens. However, there are several
      areas where the standard morphological features are insensitive, but integration
      of these parameters with histology and cytogenetic and molecular techniques may
      help us in understanding this fascinating disease.

PMID- 7632818
TI  - Rapid progression of fibrosing alveolitis and thyrotoxicosis after antithymocyte
      globulin therapy for aplastic anemia.
AB  - Antithymocyte globulin (ATG) therapy is an established form of treatment for
      aplastic anaemia and has also been used as prophylaxis against graft rejection of
      bone marrow and renal allografts. Administration of ATG preparations has been
      associated with many mild clinical reactions, as have other forms of
      immunomodulatory therapy. However, serious adverse effects appear to be rare. We
      report a case of rapidly progressive fibrosing alveolitis and thyrotoxicosis in
      relation to ATG therapy, highlighting its potential toxicity and emphasising that
      its administration should be undertaken by experienced physicians in specialised
      centres.

PMID- 7632817
TI  - Mitoxantrone and cytosine arabinoside as treatment for acute myeloblastic
      leukemia in older patients.
AB  - The majority of patients with acute myeloid leukemia (AML) are elderly, and their
      response to chemotherapy is poorer than that of younger patients. The combination
      of mitoxantrone (MTN) and cytosine arabinoside (Ara-C) is a possible alternative
      to an anthracycline/Ara-C combination for the treatment of AML in these patients.
      Of 52 older patients (> 59 years) referred over a 3.5-year period, 33 patients
      (age range 60-78 years, median 67 years) received MTN and Ara-C as therapy for
      newly diagnosed AML. MTN was administered at a dose of 12 mg/m2/day,
      intravenously, for 3 days (23 patients), or 10 mg/m2/day for 5 days (10
      patients), and Ara-C at a dose of 100 mg/m2 twice daily, intravenously, for 7
      days. Complete remission (CR) was achieved in 16/33 patients (48%). The median
      remission duration was 6 months (range 1-37 months). The median survival was 14
      months for those who achieved CR compared with 9 months for those with resistant
      disease. Two patients remain in first CR after 13 and 37 months, but three
      patients died whilst receiving consolidation therapy. In selected elderly
      patients with AML, the combination of MTN and Ara-C provides an acceptable
      alternative to an anthracycline/Ara-C regimen, with a higher CR rate than
      historical controls. However, the CR rate and remission duration remain low
      compared with those of younger patients, supporting the need to investigate new
      approaches to treatment in this population.

PMID- 7632814
TI  - Contribution of immunophenotypic and genotypic analyses to the diagnosis of acute
      leukemia.
AB  - Diagnostic accuracy in acute leukemia (AL) can be improved if traditional
      morphology and cytochemistry are supplemented with immunophenotypic and genotypic
      analyses. This multiparameter approach is of crucial importance for the
      management of patients, as it enables the identification of leukemic syndromes
      with distinct biological features and response to treatment. Immunophenotyping
      using monoclonal antibodies has been universally accepted as a useful adjunct to
      morphological criteria. This technique is particularly valuable in diagnosing and
      subclassifying acute lymphoblastic leukemia and is also essential in certain
      types of acute myeloid leukemia (AML), such as AML with minimal differentiation
      or acute megakaryoblastic leukemia. Cytogenetic findings can be quite helpful in
      establishing the correct diagnosis and can add information of prognostic
      significance. A number of specific chromosomal abnormalities have been recognized
      that are very closely, and sometimes uniquely, associated with morphologically
      and clinically distinct subsets of leukemia. An even more basic understanding of
      normal and malignant hematopoietic cells has begun to evolve as molecular biology
      begins to unravel gene misprogramming by Southern and Northern blot analysis, the
      polymerase chain reaction, and fluorescence in situ hybridization. With the
      extensive use of these techniques it has become apparent that a proportion of
      leukemias exhibit the biologically relevant molecular defect in the absence of a
      karyotypic equivalent. On the other hand, apparently uniform chromosomal
      abnormalities such as the t(1;19) (q23;p13), t(9;22) (q33;q11), t(8;14)
      (q24;q32), or t(15;17) (q21;q21) may differ at the molecular level. Data
      collected from these modern technologies have introduced a greater complexity,
      which needs to be taken into consideration to improve both the diagnostic
      precision and the reproducibility of current classifications.

PMID- 7632821
TI  - Evaluation of the Abbott automated random, immediate and continuous access
      immunoassay analyser, the AxSYM.
AB  - The new Abbott automated immunoassay analyser called AxSYM was evaluated in our
      laboratories. The AxSYM is a completely automated system that allows random
      access in combination with immediate and continuous access. Here we describe the
      evaluation of the AxSYM on three panels of analytes, thyroid, fertility and
      tumour markers. We observed good within-run reproducibility (ranging from %CV =
      3.15 to 11.37 for low assay control to %CV = 1.18 to 6.38 for high controls) as
      well as between-day and between-laboratory precision (low controls 3.44 to 14.6%
      CV and high controls 2.56 to 8.9% CV). The analytical sensitivity of the assays
      ranged from very sensitive to acceptable, but always better than claimed by the
      manufacturer. The throughput of the AxSYM in our hands was 68 tests per hour.
      Correlation between the AxSYM assays and other Abbott assays (IMx) was excellent
      (slopes ranging from 0.965 to 1.071, correlation, r = 0.964 to 0.999). Compared
      to the Tosoh AIA 1200, good correlation was observed (slopes ranging from 0.964
      to 1.111, correlation, r = 0.740 to 1.000), except for thyrotropin (slope =
      0.689, r = 0.998) and carcinoembryonic antigen (slope = 0.737, r = 0.949). We
      concluded that the AxSYM represents a new generation of random access automated
      immuno analysers with very good performance in a daily routine use. We also
      concluded that the AxSYM was very technician friendly compared to the Tosoh AIA
      1200.

PMID- 7632819
TI  - Extramedullary hematopoiesis encasing the pelvicalyceal system: CT findings.
AB  - A rare case of symmetric renal extramedullary hematopoiesis is hypothesized in a
      patient with long-standing Vaquez' disease and myelofibrosis. At CT, soft tissue
      densities were found in the renal hilar area encasing the pelvicalyceal system.
      Although there is nothing specific about the CT findings, the diagnosis can be
      suggested in the proper clinical setting. The association with generalized
      osteosclerosis is another diagnostic clue.

PMID- 7632820
TI  - Defibrination essential in the assay of ionized magnesium in mononuclear cells.
AB  - Intracellular free (ionized) magnesium concentration was measured in mononuclear
      cells isolated from healthy volunteers by use of dual wavelength fluorescence
      (indicator: mag-fura-2). We found a free Mg2+ concentration of 1.28 +/- 0.08
      mmol/l in mononuclear cells isolated from heparinized blood. When we defibrinated
      blood samples prior to the isolation step we measured 0.78 +/- 0.05 mmol/l of
      free Mg2+ in these cells. We conclude that this difference is caused by the
      platelets present in the heparinized specimens.

PMID- 7632822
TI  - Expression pattern of matrix metalloproteinases in human liver.
AB  - Antibodies were raised against seven major matrix metalloproteinases: stromelysin
      1 (MMP-3), stromelysin-2 (MMP-10), stromelysin-3 (MMP-11), interstitial
      collagenase (MMP-1), M(r) 72,000 type IV collagenase (72 kDa type IV collagenase,
      MMP-2), M(r) 92,000 type IV collagenase (92 kDa type IV collagenase, MMP-9) and
      matrilysin (PUMP, MMP-7) as well as against prolyl 4-hydroxylase, to study the
      expression of these collagenolytic enzymes in normal liver in relation to the
      activity of collagen synthesis. Tissue samples of four normal human livers, three
      hepatocellular carcinomas and one cholangiocellular carcinoma were analysed. In
      normal liver we found expression of stromelysin-1, stromelysin-3, interstitial
      collagenase, M(r) 72,000 and M(r) 92,000 type IV collagenases and varying
      expression of prolyl 4-hydroxylase. Stromelysin-2 was inconsistently detectable;
      matrilysin was not found. In hepatocellular carcinoma the expression pattern of
      matrix metalloproteinases showed only minor changes compared with the normal
      tissue; stronger signals than in normal tissue were seen for stromelysin-1, and
      stromelysin-2 was also strongly positive. M(r) 72,000 and M(r) 92,000 type IV
      collagenases and interstitial collagenase were less strongly expressed;
      stromelysin-3 was unchanged. Expression of prolyl 4-hydroxylase was also
      increased compared with normal liver. Matrilysin was only seen in
      cholangiocellular carcinoma, which showed a completely different pattern of
      matrix metalloproteinase expression. Our results show that metalloproteinases are
      expressed in human liver with much greater abundance than previously described.
      Their expression pattern is not changed fundamentally in hepatocellular carcinoma
      but is completely different from that of other tumour tissues such as
      cholangiocellular carcinoma.

PMID- 7632823
TI  - Cryopreservation and long-term storage of human low density lipoproteins.
AB  - A simple and effective technique of long-term storage of human low density
      lipoproteins (LDL) has been developed. The technique involves the addition of 1.4
      mol/l (or 10% by volume) dimethyl sulphoxide directly to a solution of the
      freshly isolated LDL in high salt buffer, and subsequent freezing and storage for
      up to 2 years at -70 degrees C. We have shown that freshly isolated LDL,
      "preserved" as described above, are able to keep their native properties for a
      long period, i.e.: a) electrophoretic behaviour in non-denaturing (or with sodium
      dodecyl sulphate, 1 milligram) polyacrylamide 2-16% gradient gel electrophoresis;
      b) immunoreactivity of apolipoprotein B (analyzed by radial immunodiffusion,
      electroimmunoassay and immunoturbidimetric assay); c) immunogeneity of
      apolipoprotein B; d) an average size of LDL particles (analyzed by electron
      microscopy); e) ability to bind with B,E-receptors of human skin fibroblasts. The
      technique can also be applied to radiolabelled LDL samples. Taking into
      consideration the labour- and time-consuming procedure of obtaining and
      characterizing LDL, and the preferred use of single well-characterized LDL
      preparation, we recommend that the above technique of LDL long-term storage be
      applied in various clinical and biomedical studies.

PMID- 7632825
TI  - A competitive polymerase chain reaction assay for reliable identification of
      Bordetella pertussis in nasopharyngeal swabs.
AB  - In order to optimize the identification of clinically relevant quantities of
      Bordetella pertussis in nasopharyngeal swabs, an automated assay introducing
      competitive polymerase chain reaction was established. A 183 base pair DNA
      fragment from a repetitive region of the Bordetella pertussis genome was
      amplified in a polymerase chain reaction. An internal control DNA with nine base
      substitutions was coamplified in the same reaction. The differentiation between
      the amplified B. pertussis DNA and the internal control was based on
      hybridisation against two different probes using Enzymun Test DNA Detection
      (Boehringer Mannheim). Nasopharyngeal swabs from serologically positive patients,
      clinically diagnosed with whooping cough, serologically negative patients after
      contact with B. pertussis and a negative group were compared. The advantages of
      competitive PCR are a reduced risk of false-positive and false-negative results
      and the possibility to differentiate between the different PCR positive groups.

PMID- 7632824
TI  - Determination of faecal fat by near-infrared spectroscopy.
AB  - The applicability of near-infrared spectroscopy to determine the amount of fat in
      faeces has been investigated. Near-infrared spectroscopy was favourably compared
      with the well known titrimetric method (Van de Kamer et al., J Biol Chem 1948;
      177:347-55). A good correlation between near-infrared spectroscopy and the
      titrimetric method was found. The measurement of faecal fat by near-infrared
      spectroscopy is found to be more precise than the manual method. Moreover, near
      infrared spectroscopy is shown to be a very simple and rapid method for measuring
      fat in faeces. However, it was shown that performing one's own calibration curve
      is necessary. Due to this necessity and the costs of the apparatus application of
      near-infrared spectroscopy is especially advantageous in laboratories with a
      substantial amount of samples to be analysed.

PMID- 7632827
TI  - State of the art of preanalysis in laboratories in Italy performing
      endocrinological tests.
AB  - We conducted an inquiry among Italian laboratories regarding the preanalytical
      phase for endocrinological tests. The form presented two questions: number of
      analyses per year and use of closed or open system for blood drawing. The
      laboratories were asked to insert the hormones' names in some boxes representing
      different materials for endocrinological tests, namely serum from plain tubes and
      from gel separator tubes, plasma from K3EDTA, Na2EDTA, lithium heparin with or
      without gel separator, sodium citrate, sodium fluoride and potassium oxalate, and
      citric acid-citrate-dextrose (ACD), and also the particular mode of storage of
      specimen, as addition of antiproteolytic substances and use of iced water. The
      analytes' list included the most common endocrinological assays. The data
      collected indicate that traditional, syringe-based systems are still widely used
      in Italy, particularly in private and small and medium-sized public laboratories.
      Serum is the most often used material for endocrinological tests. A very
      important finding was the use of gel separator tubes, wider than plan tubes, for
      obtaining serum. Finally, the laboratories demonstrated very good attention to
      the preanalytical phase, as judged from particular storage for some delicate
      analytes.

PMID- 7632828
TI  - Immunosuppressive effect induced by intraperitoneal and rectal administration of
      boar seminal immunosuppressive factor.
AB  - The immunosuppressive component was isolated from boar seminal vesicle secretion
      and administered i.p. or rectally to male mice. By means of the immunofluorescent
      method, the seminal immunosuppressive component was found on the membranes of 50
      70% of white blood cells of treated mice the first day after i.p. and the third
      day after rectal administration. The immunosuppressive component was observed on
      the membranes of 10-20% of white cells even at the 17th day after treatment.
      Intraperitoneal or rectal administration of the immunosuppressive component led
      to a decrease in the white cell concentration in blood of treated mice. These
      findings indicate that rectal deposition of semen may compromise some aspects of
      the immune system and may be an important cofactor in the development of viral or
      bacterial infections among homosexual men.

PMID- 7632826
TI  - Distinction between homozygous and heterozygous subjects with hereditary
      haemochromatosis using iron status markers and receiver operating characteristic
      (ROC) analysis.
AB  - The purpose of the present study was: 1) to evaluate which of the four iron
      status markers (serum iron, serum transferrin, serum transferrin saturation,
      serum ferritin) displayed the highest discriminatory potential in the distinction
      between homozygous patients with hereditary haemochromatosis and heterozygous
      relatives, 2) to suggest optimum cut-off values for these iron status markers,
      and 3) to demonstrate how these cut-off values change if the expected utility
      from a correct diagnosis is incorporated into the analysis. The patients and
      relatives were found by a nation-wide epidemiological survey. The study
      population consisted of 162 patients with clinically overt hereditary
      haemochromatosis and 84 asymptomatic heterozygous relatives. The statistical
      evaluation was performed using receiver operating characteristic (ROC) curve
      analysis. The diagnostic power of the iron markers is expressed as the area under
      the ROC curve. The optimum cut-off value is at the point where the slope of the
      ROC curve is equal to one. Changes in the optimum cut-off value at varying
      expected utility from a correct classification was estimated by changing the
      scaling of the ROC diagram. Serum iron and serum transferrin had the smallest
      area under the ROC curve, and were both unsuitable as discriminators. Near
      complete discrimination was obtained with serum transferrin saturation and serum
      ferritin concentrations, displaying the largest area under the ROC curve (0.991
      and 0.998). The optimum threshold value for transferrin saturation was 61%, and
      for serum ferritin concentration 800 micrograms/l. The transferrin saturation
      level reflects the presence of the haemochromatosis allele, whereas the serum
      ferritin concentration indicates the degree of iron overload.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7632829
TI  - Expression of immediate early genes in tubular cells of rat testis.
AB  - In this study we investigated the expression of the immediate early genes (IEGs)
      c-fos, c-jun, and junD on mRNA and protein levels during the spermatogenic cycle
      of the rat using Northern blotting, in situ hybridization, and
      immunocytochemistry. The expression of these IEG mRNAs and proteins exhibited
      stage-specific variations. The results suggest that IEGs take part in
      transcriptional events that are involved in regulating the proliferation and
      differentiation of spermatogenic cells during specific stages of the cycle of the
      seminiferous epithelium.

PMID- 7632830
TI  - Mouse sperm adenylyl cyclase: general properties and regulation by the zona
      pellucida.
AB  - It has been shown that the cAMP concentrations in capacitated mouse sperm can be
      increased in response to the egg's extracellular matrix, the zona pellucida (ZP),
      during the acrosome reaction. However, it is not known whether this cAMP
      elevation is caused by a stimulation of adenylyl cyclase (AC) activity or a
      decrease in cyclic nucleotide phosphodiesterase activity. In the present study
      using capacitated mouse spermatozoa, 20% and 30% of the total AC activity in the
      presence of Mg2+ and Mn2+, respectively, was measured in the sperm membrane
      fraction that contained the highest specific AC activity. As reported in other
      studies of sperm AC, Mn(2+)-supported AC activity was 15-30 times higher than
      Mg(2+)-supported AC activity. Interestingly, when the membrane fraction was
      solubilized with Lubrol-PX, an increase in specific and total Mg(2+)-supported AC
      activity was obtained while a decrease in both the specific and total Mn(2+)
      supported AC activity was observed. In the absence of detergent, the ZP
      stimulates the membrane AC in a concentration-dependent manner, but this
      stimulation is observed only when the enzyme activity is measured in the presence
      of Mg2+. Forskolin also stimulates the Mg(2+)-but not the Mn(2+)-supported AC
      activity, and this effects is not additive to or synergistic with the ZP
      stimulation of the membrane AC. Results reported in this study suggest that ZP
      mediated stimulation of membrane-associated AC may represent a mechanism by which
      the ZP affects sperm functions.

PMID- 7632831
TI  - Meiotic competence of marmoset monkey oocytes is related to follicle size and
      oocyte-somatic cell associations.
AB  - This study was conducted to investigate the relationships between oocyte meiotic
      competence, follicle size, and occyte-somatic cell associations in the marmoset
      monkey (Callithrix jacchus). Follicles were excised from ovaries of nonstimulated
      adult cyclic females (n = 6) collected on Day 7 of the follicular phase.
      Follicles were separated into size groups: large preantral (260-400 microns),
      periantral (420-640 microns), small antral (660-1000 microns), large antral (1020
      2000 microns), and preovulatory (> 2000 microns). Partially naked and
      cumulus/granulosa-enclosed oocytes (n = 473) were released from follicles and
      cultured in Waymouth's medium with 10% fetal calf serum, 1 microgram/ml human (h)
      FSH, and 10 micrograms/ml hLH. Somatic cells remaining after 46 h were removed,
      and oocytes were fixed after 48 h and mounted for viewing. Chromatin staining and
      microtubulin fluorescence labeling were used to assess progression of meiotic
      maturation and spindle normality. The follicle size distribution and
      oocytesomatic cell associations are reported. Competencies of oocytes to achieve
      germinal vesicle breakdown (GVBD) and metaphase II (MII) increased significantly
      (p < 0.001) with follicular size but not with the association of somatic cells.
      Marmoset oocytes from antral follicles resumed (GVBD) and completed (MII) meiotic
      maturation with high frequencies (98% and 72%, respectively), with no significant
      differences among size groups of antral follicles. GVBD competence was virtually
      absent in oocytes from preantral follicles (2%) and was acquired coincidentally
      with antrum formation (60%), although MII competence was attained after the
      completion of antrum formation. Partially naked oocytes from small antral
      follicles matured with a high incidence of spindle and meiotic abnormalities
      (44%). Marmoset oocyte meiotic competencies are notably higher than in any other
      nonhuman primate species studied, and a possible explanation for this phenomenon
      in relation to the stage of antrum formation is offered.

PMID- 7632832
TI  - Effect of purinergic stimulation on intracellular calcium concentration and
      transepithelial potential difference in cultured bovine oviduct cells.
AB  - Epithelial cells were removed from bovine oviducts by enzyme digestion and either
      cultured on laminin-coated coverslips (for determination of [Ca2+]i) or on
      collagen filters (for determination of transepithelial potential difference
      [pd]). Cells on coverslips were loaded with Fura-2 to monitor [Ca2+]i.
      Application of extracellular ATP induced a transient increase in [Ca2+]i in a
      dose-dependent manner. This response was abolished by thapsigargin, indicating
      that the rise in [Ca2+]i was derived from intracellular stores. The order of
      potency of the nucleotide-induced rise in [Ca2+]i was uridine triphosphate
      (UTP)>ATP>ADP. Epithelial cells were grown on collagen filters, and when mounted
      in a modified Ussing chamber exhibited an electrical pd of 1.00 +/- 0.36 mV with
      the apical side negative with respect to the basal. Application of UTP, ATP, and
      ADP to the basal side induced transient increases in pd of 1.15 +/- 0.21, 0.77 +/
      0.16, and 0.26 +/- 0.06 mV, respectively. The order of potency of the
      nucleotides in eliciting transient increases in [Ca2+]i and pd suggests the
      presence of a P2u purinergic receptor in the bovine oviduct epithelium that could
      play a role in transepithelial ion movements and hence the control of oviductal
      fluid formation.

PMID- 7632834
TI  - Local initiation of spermatogenesis in the horse.
AB  - Gross observation of testicular parenchyma of 1.5- to 2-yr-old horses reveals
      both light and dark regions. If this gross, differential shading reflects
      quantitative differences in the development of spermatogenesis and interstitial
      cell populations, the horse may prove to be a useful model for study of the
      paracrine relationships associated with initiation of spermatogenesis. The
      objective of this study was to characterize seminiferous tubules and interstitium
      of testes with gross, differential shading. Testes with both light and dark
      regions of parenchyma were obtained from horses 1.5-2 yr old and compared to
      parenchyma of fetal, 2-yr-old, or 5-yr-old horses. Stereology was used on tubular
      and interstitial components, and luminal development of seminiferous tubules was
      scored. Volume density of seminiferous tubules, percentage of tubules with large
      vacuoles or a complete lumen, and number of primary spermatocytes per gram were
      greater (p < 0.05) in light parenchyma than in dark parenchyma. The percentage of
      tubules with no lumen and the percentage of parenchyma occupied by interstitial
      space were greater (p < 0.05) in fetal and dark parenchyma than in light
      parenchyma. The number of Leydig cells per gram parenchyma was similar (p > 0.05)
      in both light parenchyma and dark parenchyma. A greater percentage (p < 0.05) of
      other (nonvascular, non-Leydig, nonmacrophage) cells was found in the dark
      parenchyma than in light parenchyma or in testes of 2- or 5-yr-old horses. The
      volume density of macrophages was notably greater (p < 0.05) in fetal and dark
      parenchyma than in light parenchyma or in testes from older horses. Variation in
      development of seminiferous tubules was not associated with the volume density of
      blood vessels. In conclusion, the gross, differential shading of equine
      testicular parenchyma with its corresponding differences in seminiferous tubular
      development is a clear example of the effect of local factors leading to the
      local initiation of spermatogenesis.

PMID- 7632833
TI  - Reproductive senescence in female Japanese monkeys (Macaca fuscata): age- and
      season-related changes in hypothalamic-pituitary-ovarian functions and fecundity
      rates.
AB  - Age- and season-related changes in gonadotropin-gonadal functions were studied in
      captive female Japanese monkeys (Macaca fuscata fuscata), with special reference
      to reproductive senescence. In experiment 1, a total of 57 nonlactating females
      at ages 3-32 yr were used. Blood samples were collected for at least one breeding
      season (September through March), and changes in plasma concentrations of LH,
      estradiol, and progesterone were examined. In experiment 2, two groups of females
      (older females, n = 5, over 21 yr old; mature females, n = 5, aged 8-12 yr)
      received s.c. injections of 50 micrograms/kg of estradiol benzoate during the mid
      breeding season. In experiment 1, ovarian functions as well as fecundity rates
      were maintained in the animals aged 5-20 yr. A decline in ovarian activity became
      apparent at 21-25 yr of age, when animals exhibited a slight increase in plasma
      LH during the breeding season. Onset of menopause occurred at around 27 yr of
      age, near the end of the life span. Menopausal females exhibited a marked
      seasonal difference in plasma LH concentrations, with high levels during the
      breeding season. In experiment 2, estradiol treatment elicited an LH surge in
      both old and mature females. The marked seasonal difference in plasma LH, as well
      as the maintenance of LH response to estradiol in menopausal females, suggests a
      possibility that biannual changes in sensitivity of the hypothalamo-hypophysial
      axis to the negative feedback action of estradiol are maintained even after
      menopause.

PMID- 7632835
TI  - Effect of oxytocin on testosterone production by isolated rat Leydig cells is
      mediated via a specific oxytocin receptor.
AB  - The effect of the neurohypophysial hormones oxytocin and arginine vasopressin
      (AVP) on testicular steroidogenesis was reevaluated by use of short-term (< 10 h)
      cultures of isolated adult rat Leydig cells. Oxytocin at 10(-9), 10(-7), and 10(
      5) M concentrations significantly increased basal testosterone production in a
      dose-dependent manner but had no effect on LH-stimulated testosterone production.
      The specificity of the effect was determined by use of the specific oxytocin
      receptor antagonist (OTA). OTA from 10(-9) to 10(-5) M concentrations inhibited
      the oxytocin-stimulated increase in testosterone production. Furthermore, the
      oxytocin agonist Thr4 Gly7 oxytocin also induced a dose-dependent increase in
      basal testosterone production. In contrast, AVP from 10(-9) to 10(-5) M
      concentrations did not consistently affect basal testosterone production by
      isolated Leydig cells, but significantly decreased LH-stimulated testosterone
      production. Inclusion of 10(-7) and 10(-5) M OTA with 10(-7) M AVP did not alter
      the inhibitory effect of the AVP. These data show that oxytocin and AVP have
      different effects on testosterone production by Leydig cells in vitro and support
      the hypothesis that oxytocin acts in the testis through a specific oxytocin
      receptor.

PMID- 7632836
TI  - Prolactin receptor expression in rat spermatogenic cells.
AB  - To identify target cells of prolactin (PRL) in the male gonad, the expression of
      prolactin receptor (PRL-R) mRNA in adult rat testes was investigated by in situ
      hybridization using a digoxigenin-labeled cRNA probe. We also investigated PRL
      binding to testicular cells in vitro. Signals for PRL-R mRNA were detected not
      only in interstitial cells but also in spermatogenic cells. Although the reaction
      was positive in all phases of spermatogonia and spermatocytes, it disappeared in
      early round spermatids. No signals were detected in elongated spermatids or
      spermatozoa. The signal intensity varied among each phase of spermatogenic cells.
      PRL-R mRNA was expressed in all stages of the cycle of the seminiferous
      epithelium. PRL-R were detected on the surface of Leydig cells, Sertoli cells,
      all phases of spermatogonia and spermatocytes, elongated spermatids, and
      spermatozoa. Ovine PRL. did not bind to round spermatids. In Leydig cells,
      pachytene spermatocytes, and spermatozoa, PRL-R were observed in relatively large
      numbers. There were fewer receptors in other phases of spermatogenic cells. These
      results indicate that PRL-R mRNA expression is almost consistent with PRL binding
      sites except for elongated spermatids and spermatozoa, and suggest that PRL may
      have direct effects on spermatogenic cells.

PMID- 7632837
TI  - Failure of the estrous cycle and spermatogenesis to respond to day length in a
      subtropical African rodent, the pouched mouse (Saccostomus campestris).
AB  - Little is known about the role of photoperiod in the control of reproduction in
      mammals from the tropics in general and, in particular, from the Afrotropics. The
      present study examined the reproductive photosensitivity of the pouched mouse
      (Saccostomus campestris: Cricetidae), a small, seasonally breeding rodent that
      occurs from about 12 degrees S to 33 degrees S in Africa. Groups of 10 laboratory
      bred male pouched mice were exposed to either long-day (16L:8D) or short-day
      (8L:16D) conditions for 14 wk, after which they were killed and the spermatogenic
      activity of the testes was assessed histologically. A group of 10 adult,
      multiparous females were exposed to long-day conditions for 3 mo, after which the
      lengths of five consecutive estrous cycles were measured. Thereafter, day length
      was reduced to 10L:14D, and after 16 days acclimation, the lengths of five
      estrous cycles were measured. Finally, day length was reduced to 8L:16D, and
      after 33 days, the lengths of five estrous cycles were measured. Day length had
      no influence on body size, testis size, or the histology of the testis, and all
      specimens were actively producing spermatozoa. The length of the estrous cycle
      (4.0 +/- 0.3 days under long-day conditions) did not change significantly with
      the decrease in photoperiod. In a third experiment, 14 multiparous and six
      nulliparous females that had been maintained under short-day conditions for 33
      days were mated and successfully reared litters.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7632838
TI  - Evidence that glutathione is involved in thermotolerance of preimplantation
      murine embryos.
AB  - Experiments were conducted to determine whether or not glutathione (GSH) is
      involved in thermotolerance responses of murine morulae. In the first experiment,
      morulae were exposed to either homeothermic temperature (37 degrees C), mild heat
      shock (40 degrees C for 1 h), severe heat shock (43 degrees C for 2 h), or a mild
      heat shock followed by severe heat shock (to induce thermotolerance). Exposure to
      mild heat shock did not affect viability and development, but severe heat shock
      reduced viability (i.e., live/dead staining) and the proportion of morulae that
      developed to blastocysts. This effect of 43 degrees C was reduced if embryos were
      first exposed to a mild heat shock of 40 degrees C. In the presence of DL
      buthionine-[S,R]-sulfoximine (BSO), an inhibitor of GSH synthesis, the ability of
      40 degrees C to confer thermotolerance was reduced. BSO decreased embryonic GSH
      content but did not decrease overall protein synthesis. In another experiment,
      administration of S-adenosyl-L-methionine, an inducer of GSH synthesis, decreased
      the deleterious effects of heat shock of 43 degrees C for 2 h on viability and
      percentage of embryos that became blastocysts. Addition of 5 microM GSH or GSH
      ester reduced the effect of 42 degrees C for 2 h on viability but not on
      continued development. The results suggest a role for GSH-dependent mechanisms in
      the processes by which murine embryos limit deleterious effects of heat shock.

PMID- 7632839
TI  - Possible role of platelet-activating factor in embryonic signaling during
      oviductal transport in the hamster.
AB  - Hamster embryos enter the uterus in pregnant females nearly one day earlier than
      unfertilized eggs in cycling females. The hypothesis that a substance derived
      from eicosanoids is released by the embryos, but not by oocytes, to hasten their
      transport to the uterus was tested by examining the effects of indomethacin,
      nordihydroguaiaretic acid (NDGA), platelet-activating factor (PAF), and PAF
      antagonists on egg transport in the hamster. Administration of indomethacin had
      no effect on embryo transport, whereas administration of NDGA delayed the
      transport of eggs to the uterus in pregnant but not in cycling hamsters. The PAF
      antagonists TCV-309 and BN-52021 delayed significantly the transport of eggs to
      the uterus in pregnant animals, but not in cycling animals; i.e., they retarded
      the passage of embryos but not of oocytes to the uterus. Administration of PAF to
      cycling hamsters hastened the oviductal transport of ova. These data suggest
      that, in the hamster, the earlier passage of embryos to the uterus as compared to
      oocytes is mediated by PAF. Thrombocytopenia was detected in early-pregnant
      hamsters, and PAF-like activity was detected in spent media of two-cell through
      morula stage hamster embryos. These results suggest that preimplantation hamster
      embryos produce PAF-like activity that mediates embryonic signaling to the
      oviduct as well as pregnancy-associated thrombocytopenia.

PMID- 7632840
TI  - Distribution and metabolism of maternal progesterone in the uterus, placenta, and
      fetus during rat pregnancy.
AB  - This study examined the in vivo distribution and metabolism of maternal
      progesterone (P4) in the rat uterus at Day 16 of pregnancy, i.e., the time of
      maximal P4 secretion, and at Day 22, one day prior to parturition. Arterial and
      uterine venous blood samples were collected at 20-min intervals from rats (n = 5
      per group) infused with [3H]-P4 for 2 h. Placentas, fetuses, and uterine tissue
      (myometrium and decidua) were obtained just prior to the end of the infusion; and
      total tritium, [3H]-P4, and lipid-soluble and water-soluble metabolite
      concentrations were determined in all blood and tissue samples. Irreversible
      extraction of P4 by the uterus and its contents was 54.2 +/- 6.0% (mean +/- SEM)
      on Day 16, and this was at least maintained to Day 22 (64.7 +/- 7.4%). Because
      uterine blood flow increases dramatically over this period, the maintenance of
      high uterine P4 extraction is likely to have contributed partly to the 41% rise
      in the metabolic clearance rate of P4 between Day 16 (147 +/- 16 ml/min per kg)
      and Day 22 (207 +/- 13 ml/min per kg). Uterine tissue levels of [3H]-P4 exceeded
      (1.6-fold) those in arterial blood on Day 16, but this difference was not evident
      at Day 22. In contrast, the concentration of [3H]-P4 in the placenta was lower
      than that in arterial blood at Day 16 (66% lower) and Day 22 (25% lower), even
      though total tritium concentrations were similar at these sites. [3H]-P4 was also
      lower in fetal tissue compared with maternal arterial blood on both days of
      pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7632842
TI  - Expression of carbonic anhydrase isoenzymes IV and II in rat epididymal duct.
AB  - Acidic epididymal fluid mainly accounts for sperm quiescence during storage in
      the epididymis. Carbonic anhydrase (CA) is an enzyme involved in proton and
      bicarbonate secretion in various epithelia. Therefore, we elucidated the
      distribution of the cytoplasmic (CA II) and membrane-associated (CA IV)
      isoenzymes in rat epididymis using polyclonal rabbit antisera to these isoenzymes
      in conjunction with immunohistochemical and immunoblotting techniques. CA IV was
      localized in the apical plasma membrane of principal epithelial cells in the
      distal caput, corpus, and proximal cauda epididymides, the staining intensity
      being most intense in the corpus segment. The epithelium of the ductus deferens,
      seminal vesicle, and ventral prostate was devoid of staining. CA II was present
      in the narrow cells of the initial segment and in the epithelial cells of the
      distal caput, corpus, and proximal cauda epididymides. Immunoblotting of
      different epididymal segments for CA IV and II revealed with anti-CA IV serum a
      distinct 39-kDa polypeptide band in the corpus segment and with anti-CA II serum
      a 29-kDa polypeptide band in all segments, with the band most intense, however,
      in the corpus segment. Our results imply that in rat epididymis both bicarbonate
      reabsorption and proton secretion are involved in epididymal fluid acidification.
      By analogy with the kidney proximal tubule, we suggest that CA IV is involved in
      bicarbonate reabsorption mainly occurring in the corpus epididymidis. The
      presence of CA II in epididymal epithelial cells is probably involved in the
      supply of protons for secretion mediated by various ion transport mediators.

PMID- 7632841
TI  - Low and high concentrations of gonadotropins differentially regulate hormone
      production by theca interna and granulosa cells from bovine preovulatory
      follicles.
AB  - Mammalian preovulatory follicles produce primarily estradiol and androgens before
      the preovulatory gonadotropin surge. In cattle, the LH/FSH surge triggers a rapid
      decrease in estradiol and androgen production and a dramatic increase in
      progesterone and oxytocin biosynthesis. It is unclear how changes in gonadotropin
      concentrations in vivo regulate this follicular/luteal phase shift in hormone
      production. To address this question, theca interna and granulosa cells were
      isolated from preovulatory follicles of Holstein heifers approximately 24 h
      before the expected time of the LH/FSH surge and cultured in defined medium
      containing insulin (1 microgram/ml), with varying doses of LH or FSH (0, 1, 2, 4,
      8, 16, 32, 64, or 128 ng/ml). Media were collected and replaced every 24 h for 3
      days, and assayed for androstenedione and progesterone in theca interna cultures,
      and for estradiol, progesterone and oxytocin in granulosa cell cultures. After
      the first day of culture (24-72 h), only very low doses of LH (2 or 4 ng/ml)
      enhanced (p < 0.05) androstenedione secretion by theca interna cultures above
      control levels, whereas progesterone secretion was increased by a wide range of
      LH concentrations (p < 0.05), with maximal progesterone secretion at high doses
      of LH. Likewise, after the first day of culture (24-72 h), estradiol secretion by
      granulosa cells was stimulated only by low doses of FSH and was inhibited at
      higher concentrations relative to control cultures (p < 0.05), whereas the
      production of oxytocin and progesterone was enhanced maximally by high
      concentrations of FSH (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7632843
TI  - Differential effects of a steroidal antiestrogen, EM-139, on prostaglandin and
      cyclic adenosine 3',5'-monophosphate production in the circular and longitudinal
      layers of bovine myometrium.
AB  - The regulation of prostaglandin (PG) production and cAMP generation was studied
      in vitro in cultured smooth muscle cells isolated specifically from the circular
      or longitudinal layers of the bovine myometrium. We found that prostacyclin
      (PGI2) was the principal PG produced by the myometrium, especially in the
      longitudinal layer, followed closely by PGE2 and marginally by PGF2 alpha. The PG
      production (fg/ml, mean +/- SD) in the circular and longitudinal layers was,
      respectively, PGE2 (424.4 +/- 162.0) > PGI2 (189.5 +/- 19.0) > PGF2 alpha (9.5 +/
      3.0) versus PGI2 (751 +/- 36) > PGE2 (515.7 +/- 94.0) > PGF2 alpha (16.3 +/-
      3.0); production was stimulated up to 15-fold 24 h after addition of phorbol 12
      myristate (PMA; 100 nM). Hormonal control of PG production was assessed by use of
      a steroidal antiestrogen, EM-139. PG production was inhibited in a concentration
      dependent manner by EM-139 in both circular and longitudinal layers, with maximal
      inhibition at 1 microM. In parallel studies, chronic treatment with EM-139
      resulted in significant increases in isoproterenol-induced cAMP production in
      both muscle layers, but more especially in the circular layer. This
      antiestrogenic effect was reversed by addition of 17 beta-estradiol. These
      results indicate that the two smooth muscle layers of the bovine myometrium have
      distinct patterns of PG production and that the adenylate cyclase/cAMP response
      of the circular layer is more sensitive to estrogen modulation. Our findings with
      a cell culture model of separated myometrial layers provide strategic information
      for a better understanding of the regulation of uterine contractility during
      pregnancy.

PMID- 7632844
TI  - Developmental and hormonal regulation of DNA methyltransferase in the rat testis.
AB  - Changes in DNA methylation patterns during gametogenesis have been implicated in
      the regulation of germ cell development and genomic imprinting. Cytosine
      methylation is catalyzed by the enzyme DNA (cytosine-5)-methyltransferase (DNA
      MTase). The objective of this study was to determine the presence and study the
      developmental and hormonal regulation of DNA MTase expression in the rat testis.
      Northern blots of RNA isolated from 10 different adult rat tissues were used to
      determine tissue-specific differences in transcript size and abundance of DNA
      MTase. The developmental regulation of DNA MTase in the rat testis was examined
      by use of Northern blots of testicular and isolated germ cell RNA from rats
      ranging in age from 7 to 91 days. For a better understanding of the hormonal
      regulation of DNA MTase in the rat testis, adult rats were hypophysectomized and
      4 wk later (Day 0) received 24-cm testosterone silastic implants; controls were
      sham hypophysectomized. At Days 0, 3, 7, 14, 28, and 56, one testis from each rat
      (n = 4/group) was used to prepare total RNA. Examination of DNA MTase mRNA
      expression in different rat tissues demonstrated the existence of a single 5.2-kb
      transcript; up to 5-fold tissue-specific variations in the levels of DNA MTase
      mRNA between the tissue with the highest expression, spleen, and that with the
      lowest expression, prostate; and significant levels of expression in the testis
      (three times prostate levels). During testicular development, DNA MTase mRNA
      levels were highest at 7-21 days of age and decreased by 45% by Day 28; mRNA
      levels decreased further to reach steady adult levels by Day 42.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7632845
TI  - Phosphatidylcholine-binding proteins of bovine seminal plasma modulate
      capacitation of spermatozoa by heparin.
AB  - Bovine seminal plasma (BSP) contains four similar acidic proteins, previously
      designated as BSP-A1, BSP-A2, BSP-A3, and BSP-30-kDa. These proteins are secreted
      by the seminal vesicles and coat the surface of the spermatozoa after
      ejaculation. The binding site of BSP proteins on the sperm surface has been
      identified as choline phospholipids on the plasma membrane. This study was
      undertaken to determine whether BSP proteins modulate capacitation of bovine
      spermatozoa induced by heparin. Bovine epididymal spermatozoa were washed and
      incubated in buffer containing BSP proteins and then washed and incubated with
      heparin. The percentage of capacitated spermatozoa was determined under the
      microscope after the acrosome reaction has been initiated with the addition of
      lysophosphatidylcholine. The results demonstrated that epididymal sperm undergo
      the acrosome reaction only in the presence of BSP proteins. This effect was
      concentration-dependent and reached a maximum level of a 3-5-fold increase at 20
      40 micrograms/ml BSP protein concentrations. In contrast, ribonuclease (purified
      from bovine seminal fluid) or seminal fluid proteins depleted of BSP proteins (by
      sequential absorption of BSP proteins on gelatin-Agarose and DEAE-Sephadex
      columns) showed no significant potentiating activity. The purified BSP proteins
      were more active than crude alcohol precipitates of bovine seminal plasma. These
      results indicate that BSP proteins are regulatory factors of capacitation.

PMID- 7632846
TI  - Characterization of murine pregnancy decidua transforming growth factor beta. I.
      Transforming growth factor beta 2-like molecules of unusual molecular size
      released in bioactive form.
AB  - A novel type of bioactive transforming growth factor beta 2 (TGF beta 2)-related
      immunosuppressive activity, lower in molecular mass (20-23 kDa) than a
      conventional TGF beta 2 standard (25 kDa), has been shown to be released by non-T
      non-B suppressor cells of murine decidua into fetal bovine serum (FBS)-containing
      tissue culture medium during a 48-h incubation at 37 degrees C. Substitution of a
      serum-free medium has allowed direct PAGE-Western blotting and the demonstration
      in supernatant (prior to incubation at 37 degrees C) of a TGF beta 2
      immunoreactive doublet at a higher molecular mass (26 and 27 kDa) than the
      standard but with apparent immunosuppressive activity. When decidua were
      incubated in serum-free medium at 37 degrees C, immunosuppressive activity in the
      supernatant increased to peak at 18 h in association with the appearance of the
      previously described lower molecular mass species of molecule. The doublet did
      not appear to be the result of glycosylation of a conventional 25-kDa TGF beta 2
      and could be converted into the lower molecular mass form by incubation for 18 h
      at 37 degrees C, with pH 4.5 but not with pH 7.5 buffer; this incubation in the
      absence of decidual cells was not accompanied by increased immunosuppressive
      activity. This transformation could be blocked by a brief heating of the
      supernatant to 80 degrees C for 10 min to destroy enzymes present in supernatant
      prior to mixing with the acidic buffer, but biologic activity neutralizable by
      anti-TGF beta 2 was retained.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7632847
TI  - Effects of relaxin administration in early gestation or prior to mating on
      uterine length and fetal survival in gilts.
AB  - The objective of this research was to determine the effect of administration of
      porcine relaxin to gilts during early gestation, or during the follicular phase
      of the estrous cycle immediately preceding mating, on the length of the uterus
      and consequently the number of surviving fetuses. Experiment 1 determined the
      individual and combined effects of 10 days of administration of relaxin (0.5 mg,
      4 times daily), estradiol benzoate (1 mg, 2 times daily), and progesterone (50
      mg, 2 times daily) on uterine wet weight and length in 58 ovariectomized 8-mo-old
      pubertal gilts. Relaxin alone had no effect on either uterine length or wet
      weight. Estrogen increased uterine wet weight, and this effect was augmented by
      relaxin. Progesterone increased uterine length, and this effect was augmented by
      estrogen. Combined treatment with progesterone, estrogen, and relaxin increased
      both uterine length and wet weight maximally. Experiment 2 determined the effects
      of relaxin administration in early gestation or prior to mating on uterine length
      and fetal survival in 75 unilaterally ovariectomized-hysterectomized gilts.
      Relaxin (0.5 mg, 4 times daily) was administered during three treatment periods,
      and uteri were collected on Day 40 of gestation. In this study, relaxin
      administration from Days 11 to 20 of gestation reduced the number of live fetuses
      (p = 0.01) and percentage survival (p = 0.01) and resulted in shorter uterine
      length (p = 0.01) and lower uterine wet weight (p = 0.03) than in controls, but
      did not affect length of uterus or uterine dry weight. Relaxin administration
      from Days 22 to 31 of gestation did not influence fetal survival, uterine length,
      uterine length per fetus, uterine wet weight, or uterine dry weight.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7632848
TI  - Functional maturation of the pituitary-gonadal axis in the neonatal female rat.
AB  - The development onset of the pituitary feedback response to LH/hCG-stimulated
      ovarian activity was studied in the neonatal rat. A single injection of hCG (600
      IU/kg BW) was administered to groups of rats between 1 and 10 days of age, and
      the responses, i.e., ovarian estradiol (E2), progesterone (P), and testosterone
      (T) production as well as serum LH were monitored 3 days later. The first
      significant increase in ovarian T and E2 contents occurred in rats treated on Day
      8 of life, and the first significant increase in P content occurred when hCG was
      administered at the age of 9 days. A significant decrease in serum LH, 3 days
      after hCG injection, was observed for the first time in animals treated on Day 7,
      but not in those aged 1-6 days. To study whether the appearance of the ovarian
      response to LH is dependent on FSH, rats received combined treatment with
      recombinant human (rec)FSH on Days 3-8 (0.3 IU s.c. twice daily) and a single
      injection of hCG (600 IU/kg BW s.c.) on Day 6. The elevated FSH levels from Day 3
      onward advanced the suppression of the serum LH level after hCG injection,
      suggesting that enhanced action of FSH promotes the appearance of functional LH
      receptors neonatally. It was concluded that 1) the negative feedback of ovarian
      activity on pituitary LH secretion is functional in the neonatal rat from Day 10
      of life; 2) increased intraovarian T levels reflect the androgenic dominance of
      this early feedback action; and 3) elevated postnatal levels of FSH may advance
      the onset of the ovarian response to LH/hCG stimulation.

PMID- 7632849
TI  - Production of viable bovine blastocysts in defined in vitro conditions.
AB  - Our purpose was to obtain viable blastocysts via in vitro maturation,
      fertilization, and culture (IVMFC) in serum- and BSA-free media (defined
      conditions) and to document viability by pregnancy initiation following embryo
      transfer (ET). Oocytes were matured in modified TCM 199 (mTCM 199) with 100
      micrograms/ml ovine (o)LH, inseminated in TALP- or defined medium (DM)-based
      media, and cultured up to 9 days in synthetic oviductal fluid (SOF) prepared with
      6 mg/ml polyvinyl alcohol (PVA) instead of BSA and buffered with 25 mM HEPES with
      experimental modifications. Modifications for embryo culture included
      supplementation with Minimum Essential Medium amino acids (MEM), Minimum
      Essential Medium nonessential amino acids (NEA), the combination of MEM and NEA,
      citrate (c; 0.5 mM), glutamine (1 mM), or combinations of these. Proportions of
      immature oocytes selected for IVM that cleaved (IVF) and that reached the
      blastocyst stage in SOF were 66.3% and 10.9%, respectively. Supplementation of
      SOF with citrate and nonessential amino acids (i.e., c-SOF + NEA) enabled 85.1%
      cleavage and 42.6% blastocyst development of oocytes selected for IVM. In
      conjunction with IVM in mTCM 199 plus 100 micrograms/ml oLH and IVC in c-SOF +
      NEA, efforts to eliminate protein from the fertilization medium revealed modified
      DM (mDM) prepared with PVA instead of BSA to be superior to TALP prepared with
      PVA; IVMFC data for blastocyst development were 27.4% vs. 18.2% (p < 0.05),
      respectively. The use of mDM for sperm preparation and IVF yielded comparable
      blastocyst development when either BSA or PVA was included.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7632850
TI  - Effect of protein kinase C stimulators on zona pellucida binding and the acrosome
      reaction of macaque sperm.
AB  - Macaque sperm require treatment with dibutyryl cAMP (dbcAMP) and caffeine (termed
      activators; ACT) to fully capacitate in vitro. Previous studies have shown that
      treatment with ACT also increases sperm binding to the macaque zona pellucida and
      enhances the induction of acrosome reactions of the bound sperm. This study
      investigated whether phorbol 12-myristate 13-acetate (PMA) and 1,2-dioctanoyl-sn
      glycerol (DOG), which stimulate protein kinase C (PKC), can also increase sperm
      binding to the zona pellucida and/or enhance induction of the acrosome reaction
      of bound sperm. Cynomolgus macaque sperm were centrifuged through 60% Percoll and
      then were washed with modified Biggers, Whitten and Whittingham (BWW) medium and
      incubated for 2.5 h at 37 degrees C with 5% CO2, ACT, PMA, or DOG was added to
      sperm during the last 15-30 min of incubation. Sperm were evaluated immediately
      after incubation for motility and acrosomal status. Macaque oocytes were
      coincubated with stimulated sperm suspensions in BWW medium for 30 sec (pulse).
      Half of the oocytes were removed to sperm-free medium and further incubated for 1
      h (chase). When assessed after the pulse period, sperm-zona binding increased
      significantly after ACT treatment compared to that in untreated controls. DOG but
      not PMA treatment had a similar effect on sperm binding PMA, DOG, and ACT
      treatment increased the percentage of acrosome reactions in sperm bound to the
      zona following the 30-sec pulse compared to the percentage in controls. Inactive
      analogs of PMA and DOG had no effect on sperm-zona binding or the percentage of
      acrosome reactions (% AR) of bound sperm.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7632851
TI  - Evaluation of extracellular matrices and the plasminogen activator system in
      sheep inner cell mass and trophectodermal outgrowth in vitro.
AB  - Effects of extracellular matrices (ECM) and the plasminogen activator (PA) system
      on outgrowth of sheep inner cell masses (ICM) and trophectoderm in vitro were
      investigated. Experiment 1 evaluated the effects of plasminogen and ECM type on
      ICM and trophectodermal outgrowth, on glass Lab-Tek chamber slides coated with
      collagen IV, fibronectin, or laminin. ICM outgrowth areas were reduced (p < 0.05)
      by plasminogen and were greatest (p < 0.05) on fibronectin. Trophectodermal
      outgrowth was not supported in this system. Experiment 2 evaluated the effects of
      PA inhibitor-2 (PAI-2) or antiserum to urokinase-type PA (anti-uPA) on ICM
      outgrowth on fibronectin. Numbers of cells in the outgrowths were increased (p <
      0.05) with PAI-2, and anti-uPA had no effect (p > 0.10). Experiment 3 evaluated
      the relationship between PA production and ECM type on ICM and trophectodermal
      outgrowth in microdrop cultures. PA production by ICM was greatest (p < 0.05) on
      fibronectin, but no differences (p > 0.10) were observed for trophectoderm. PA
      production was not correlated with ICM outgrowth areas (r = -0.12; p = 0.72) or
      numbers of cells in the ICM outgrowths (r = 0.09; p = 0.74) but was correlated
      with ICM areas (r = 0.75; p < 0.01) and numbers of cells in trophectodermal
      outgrowths (r = 0.57; p = 0.01). These results suggest that type of ECM, culture
      system, and alterations in the PA system influence cellular outgrowths by ICM and
      trophectoderm.

PMID- 7632852
TI  - Effects of endothelins on mechanical activity and inositol phosphate production
      in pregnant rat myometrium.
AB  - Endothelins (ETs) caused concentration-dependent contraction in pregnant rat
      myometrium. ET-2 was as potent as ET-1 in affecting contractile responses,
      whereas ET-3 was considerably less potent than ET-1 or ET-2. ETs also increased
      inositol phosphate (IP) production in a dose-dependent manner, with IP production
      paralleling the contractile response. The rank order of potency for both the
      contractile responses and IP production was ET-1 = ET-2 > ET-3. When we compared
      the important oxytocic agent oxytocin, we found that oxytocin (10(-7) M) strongly
      increased contractility and IP production, and the responses were comparable to
      those elicited by ET-1 (10(-7) M) and ET-2 (10(-7) M). These results suggest that
      ET-induced myometrial contraction involves phospholipase C activation, and that a
      subtype of endothelin receptor existing in pregnant rat myometrium could be
      classified as ETA.

PMID- 7632854
TI  - [Hygienic aspects of emergency care: principles, requirements and reality].
AB  - In preclinical emergency and rescue medicine, on-target and often improvised and
      smooth work is essential. Thus, some reductions of clinical standards must be
      accepted but cannot excuse fundamental mistakes. Hygienic protection of patients
      and medical staff are both equally important; however, preserving the vital
      functions of patients deserves top priority. In Germany, official guidelines
      govern the hygienic equipment of ambulance cars and hygienic management during
      and after transport both in routine and special cases. Disinfection of skin,
      hands and surfaces and hygienic protection of the medical staff predominate in
      daily work. Standard hygienic procedures during application of venous leads,
      intubation and artificial ventilation and correct handling of sterile materials
      should also be considered. The main goal of teaching is routine establishment of
      basic hygienic procedures, and, in addition, creation of sufficient hygienic
      basic knowledge for assessment and control of unusual situations.

PMID- 7632853
TI  - [Microcirculation and inhalation anesthetics].

PMID- 7632855
TI  - [Clinical randomized controlled studies in anesthesiology according to quality
      guidelines of good clinical practice. 2: Principles of implementation, analysis,
      publication and evaluation].
AB  - This article was written to give researchers and clinicians a short synopsis of
      ethical and thorough design, conduct, analysis, publication, and interpretation
      of randomised controlled clinical trials according to the European quality
      standards of Good Clinical Practice (GCP). The paper consists of two parts. In
      the first part we introduce important elements of study design, especially study
      hypothesis, criteria of inclusion and study population, sample size calculation,
      validity considerations, bias and confounding, randomisation, stratification, and
      masking of treatment assignment. Different treatment allocation like multiple
      parallel groups, factorial experiment, cross-over, and sequential design are
      presented. Requirements of ethical standards according to the Declaration of
      Helsinki are discussed for their necessity in any experimentation in humans.
      Principles of informed consent are demonstrated with emphasis on special
      conditions in anaesthesia, emergency medicine, and intensive care research. In
      the second part of this article we explain issues of baseline assessment,
      experimental intervention, data recording, and data monitoring, particularly of
      negative or hazardous treatment effects. Topics of data analysis and reporting of
      trial results in publications are illustrated with regard to their influence on
      subsequent interpretation.

PMID- 7632856
TI  - [Effects of desflurane on liver microcirculation in comparison with isoflurane
      and pentobarbital. An intravital microscopy study in the rat].
AB  - OBJECTIVE: It is well known that the volatile anaesthetics halothane, enflurane
      and isoflurane alter hepatic blood flow in a dose-dependent manner. However,
      there are only a few studies investigating the effect of the new anaesthetic
      desflurane on the hepatic blood flow. In particular no information is available
      about the influence of desflurane on liver microcirculation. Therefore, the aim
      of this study was to evaluate the effects of desflurane in comparison to
      isoflurane and pentobarbital on microcirculation of the liver in vivo using
      intravital fluorescence microscopy. MATERIALS: 18 female Sprague-Dawley rats were
      anaesthetised with pentobarbital sodium, tracheotomised and mechanically
      ventilated using a rodent ventilator. A midline laparotomy was performed for
      later intravital microscopy of the liver. At the beginning of the one-hour
      ventilation period the animals were assigned to one of the following groups:
      isoflurane 0.75 MAC, desflurane 0.75 MAC and pentobarbital group. Animals of the
      pentobarbital group received additionally 25 mg/kg pentobarbital intravenously.
      After 60 min of ventilation and continuous monitoring of the systemic circulation
      the hepatic microcirculation was investigated by intravital fluorscence
      microscopy. RESULTS: Mean arterial blood pressure decreased slightly in the
      isoflurane and the desflurane groups compared to the pentobarbital group. Neither
      isoflurane nor desflurane did affect the sinusoidal diameters or the sinusoidal
      blood flow compared to the pentobarbital group. CONCLUSION: Hepatic
      microcirculation is not affected by one-hour anaesthesia with 0.75 MAC isoflurane
      or desflurane in comparison to pentobarbital.

PMID- 7632857
TI  - Statistical modelling in analysis of outcome after trauma Glasgow-Coma-Scale and
      Innsbruck-Coma-Scale.
AB  - AIM OF THE STUDY: The current study investigated the Glasgow-Coma-Scale (GCS) and
      the Innsbruck-Coma-Scale (ICS) for accuracy and reliability of prehospital
      prediction of non-survival. METHODS: 254 patients were scored immediately after
      trauma. RESULTS: Both scales equally predicted non-survival with low scores (p <
      0.001). The ICS was slightly better in overall prediction of patient outcome
      (ICS: 84.98%; GCS: 82.68%), but more importantly, statistical analysis (logistic
      regression model) showed a greater distance between the median scores of
      survivors and non-survivors, when scored with the ICS (survival: 12; non
      survival: 3) than when scored with the GCS (survival: 7; non-survival: 4).
      CONCLUSION: The results of the present study not only suggest that it is possible
      to predict mortality prior to therapy for any individual GCS and ICS coma score,
      but also indicated the ICS to be safer to use than the GCS because of the greater
      distance of the median scores for survivors and non survivors.

PMID- 7632859
TI  - [Alfred Kirstein (1863-1922)--pioneer in direct laryngoscopy].
AB  - On April 23rd 1895, in Berlin, Alfred Kirstein performed the first direct
      examination of the interior of the larynx. 23 days after his first view of
      larynx, he gave a comprehensive demonstration of autoscopy to the Berlin Medical
      Association. Until then laryngologists had been content with the technique of
      indirect laryngoscopy using mirrors, a method popularised by Garcia, Turck and
      Czermak. Kirstein named the combination of the electroscope and the
      oesophagoscope "The autoscope" and direct examination of the larynx he termed
      "autoscopy". Despite the infancy of autoscopy and the autoscope, Kirstein already
      recognised the potential of his new discovery. He reported that the removal of
      foreign bodies from the trachea must be easier through an autoscope then by means
      of a tracheostomy; furthermore, catheterisation of the bronchi should now present
      no great difficulties. The similarity between the blades he used and those
      described in the 1940s by Macintosh and Miller is remarkable.

PMID- 7632858
TI  - [Education of the medical student in first aid, emergency and disaster medicine-
      the Graz model].
AB  - In Austria emergency and disaster medicine is a young interdisciplinary subject.
      It is only a borderline discipline encompassing different medical subjects and
      was subdivided into emergency medicine for medical doctors only and first-aid for
      lay people and emergency technicians. In fact, since emergency medicine without
      first-aid can't be successful, the Department of Anaesthesiology at the
      University of Graz let all students of the medical faculty have a comprehensive
      education in the treatment of injured of acutely ill patients. According to the
      three steps of the study lectures and practices, all parts of first-aid,
      emergency and disaster medicine were offered. In spite of the short time since
      this has been running, we found a good acceptance and we hope to increase the
      interest evinced by medical students in our training programme.

PMID- 7632861
TI  - [Tricyclic antidepressive drugs should be discontinued preoperatively: contra].

PMID- 7632860
TI  - [Tricyclic antidepressive drugs should be discontinued preoperatively: pro].

PMID- 7632862
TI  - [Severe legionellosis after abuse of anti-inflammatory drugs--diagnostic and
      intensive care aspects based on a case report].
AB  - Legionella infections are getting increasingly important as causes of severe
      pneumonias or of acute respiratory insufficiency. Consumptive or
      immunosuppressive underlying diseases such as diabetes mellitus, cardiac
      insufficiency, alcohol-induced liver damage, malignant tumours or drug-induced
      immunosuppression after organ transplantation, are among the risk factors.
      Diagnosis is based on direct identification of the pathogen from body secretions
      by means of direct immunofluorescence. The serological immunoresponse often takes
      place long after outbreak of the disease or fails entirely to appear and is
      therefore only suitable for retrospective confirmation. Therapy of choice is an
      intravenous administration of erythromycin. There are now increasing pointers to
      the efficiency of fluoroquinolone antibiotics, such as ciprofloxacin. We report
      on the course of a severe case of legionnaire's disease with multiple organ
      failure occurring in a patient after bone marrow depression induced by anti
      inflammatory drugs. Treatment erythromycin resulted in a marked cholestasis, so
      that antibiotic treatment was changed to ciprofloxacin. This therapy as well as
      the supportive intensive-care treatment eventually led to the patient's complete
      recovery. Based on the case report, fundamental aspects of diagnostics,
      antibiotic treatment, intensive-care treatment and prognosis of severe cases of
      legionellosis are discussed.

PMID- 7632863
TI  - [Apnoeic oxygenation in Boerhaave syndrome].
AB  - Boerhaave's syndrome (Hermann Boerhaave, 1724 [5]) stands for the atraumatic
      spontaneous rupture of the oesophagus, and still represents a life-threatening
      situation. Contrary to the surgical approach, the anaesthesiological management
      has been largely neglected so far. CASE REPORT: The present case report
      introduces a patient requiring surgical therapy due to a belatedly diagnosed
      rupture of the oesophagus. In agreement with the surgeon, endotracheal intubation
      was performed using a single-lumen oral Woodbridge tube. During left thoracotomy,
      artificial ventilation sometimes obstructed the surgeons. Following a life
      threatening intrathoracic venous bleeding (after additional right thoracotomy),
      the situation became almost adverse, since the surgeon could not stop the
      bleeding due to the movement of the lungs. Ventilation was therefore stopped. The
      oxygen supply was provided 20 min by application of the so-called apnoeic
      oxygenation, first described in 1908 by the German surgeon Franz Volhard (15).
      Using the filled 2.5l reservoir bag of the circle circuit as the oxygen source
      (CPAP 10 cm H2O), oxygenation was maintained by refilling the bag after its
      volume had been decreased due to the patient's ongoing O2 consumption. Starting
      with an initial paO2 value of only 400mmHg (despite pAO2 approximately 670 mmHg,
      i.e. intrapulmonary right-left shunt of approx. 10-15%), the paO2 declined to 100
      mmHg during the 20 min of apnoeic oxygenation (i.e. a drop by 15 mmHg per
      minute), whereas arterial pCO2 increased by 50 mmHg to a value of 90 mmHg, as
      stated recently in literature [18]). No relevant changes of ECG, heart rate,
      blood pressure and partial arterial oxygen saturation (pulse oxymeter) occurred.
      CONCLUSION: During thoracic operations adverse situations may arise from the two
      antipodes artificial ventilation and acceptable surgical access. Alternative
      respiratory techniques, e.g. one-lung anaesthesia and/or high-frequency jet
      ventilation, are not always applicable, although the present case report
      indicates that a double lumen tube should be recommended. However, the clinical
      use of oxygenation by apnoeic oxygenation is a useful measure that can be
      realised in a simple and safe manner. The present case report may help to
      consider this particular alternative also during thoracic surgery (no influence
      of FRC size on pAO2 decrease). If applied correctly, apnoeic oxygenation
      obviously increases both the flexibility of the anaesthesist and patient safety,
      and additionally provides the ability of safe acting in clinical routine settings
      as well as during emergencies. In summary, knowledge of this technique of
      oxygenation seems to be an integral part of serious anaesthesiological education
      and clinical management.

PMID- 7632864
TI  - The incidence of aspiration with the laryngeal mask for ambulatory surgery.

PMID- 7632865
TI  - Nerve regeneration: basic and applied aspects.
AB  - Increased knowledge is shedding new light on our understanding of central and
      peripheral nerve anatomy and molecular biology and function. New tools and
      methods provide important methods for the study of the behavior of cells, axons,
      and receptors. This review discusses the current state of that knowledge, with
      particular regard to the efficacy of the Seddon classification of nerve injury.
      The correlation of that new information to damage and repair of the peripheral
      sensory nerve, especially the inferior alveolar and lingual nerves, serves to
      highlight the progress and problems that exist.

PMID- 7632867
TI  - Bionutrition and oral cancer in humans.
AB  - Tobacco (smoking and smokeless) use and excessive consumption of alcohol are
      considered the main risk factors for oral cancer (ICD9 140-149). Conspicuous
      national and international variations in oral cancer incidence and mortality
      rates, as well as observations in migrant populations, raise the possibility that
      diet and nutritional status could be an important etiologic factor in oral
      carcinogenesis. As shown in this report, abuse of alcohol and tobacco has serious
      nutritional implications for the host, and generates increased production of
      reactive free radicals as well as eliciting immunosuppression. Maintenance of
      optimal competence of the immune system is critical for cancer surveillance.
      Active oxygen species and other reactive free radicals mediate phenotypic and
      genotypic alterations that lead from mutation to neoplasia. Consequently, the
      most widely used chemopreventive agents against oral cancer (e.g., vitamins A, E,
      C, and beta-carotene) are anti-oxidants/free radical scavengers. These anti
      oxidants, both natural and synthetic, neutralize metabolic products (including
      reactive oxygen species), interfere with activation of procarcinogens, prevent
      binding of carcinogens to DNA, inhibit chromosome aberrations, restrain
      replication of the transformed cell, suppress actions of cancer promoters, and
      may even induce regression of precancerous oral lesions such as leukoplakia and
      erythroplakia. Malnutrition is characterized by marked tissue depletion of anti
      oxidant nutrients, including GSH (gamma-glutamyl-cysteinyl-glycine), a key
      cellular anti-oxidant as well as a modulator of T-cell activation. GSH or its
      precursor cysteine inhibits activation of the nuclear transcription factor
      kB(NFkB), and has been shown to be protective against chemically induced oral
      cancer and leukoplakia. Alcohol-, tobacco-, and/or malnutrition-induced
      immunosuppression promotes impaired salivary gland function and oral mucosal
      immunity, a prominent reduction in the number of helper CD4 cells with less
      marked changes in number of suppressor T-cells, and depressed NK cell activity,
      among others. These suggest a breakdown in capacity or the malnourished to mount
      effective tumor surveillance. This review article underscores the compounding but
      important roles of nutritional/dietary factors in the long-established causal
      link between abuse of alcohol and tobacco (smoking and smokeless) and oral
      cancer.

PMID- 7632866
TI  - Prenatal craniofacial development: new insights on normal and abnormal
      mechanisms.
AB  - Technical advances are radically altering our concepts of normal prenatal
      craniofacial development. These include concepts of germ layer formation, the
      establishment of the initial head plan in the neural plate, and the manner in
      which head segmentation is controlled by regulatory (homeobox) gene activity in
      neuromeres and their derived neural crest cells. There is also a much better
      appreciation of ways in which new cell associations are established. For example,
      the associations are achieved by neural crest cells primarily through cell
      migration and subsequent cell interactions that regulate induction, growth,
      programmed cell death, etc. These interactions are mediated primarily by two
      groups of regulatory molecules: "growth factors" (e.g., FGF and TGFalpha) and the
      so-called steroid/thyroid/retinoic acid superfamily. Considerable advances have
      been made with respect to our understanding of mechanisms involved in primary and
      secondary palate formation, such as growth, morphogenetic movements, and the
      fusion/merging phenomenon. Much progress has been made on the mechanisms involved
      in the final differentiation of skeletal tissues. Molecular genetics and animal
      models for human malformations are providing many insights into abnormal
      development. A mouse model for the fetal alcohol syndrome(FAS), a mild form of
      holoprosencephaly, demonstrates a mid-line anterior neural plate deficiency which
      leads to olfactory placodes being positioned too close to the mid-line, and other
      secondary changes. Work on animal models for the retinoic acid syndrome (RAS)
      shows that there is major involvement of neural crest cells. There is also major
      crest cell involvement in similar syndromes, apparently including hemifacial
      microsomia. Later administration of retinoic acid prematurely and excessively
      kills ganglionic placodal cells and leads to a malformation complex virtually
      identical to the Treacher Collins syndrome. Most clefts of the lip and/or palate
      appear to have a multifactorial etiology. Genetic variations in TGF alpha s, RAR
      alpha s, NADH dehydrogenase, an enzyme involved in oxidative metabolism, and
      cytochrome P-450, a detoxifying enzyme, have been implicated as contributing
      genetic factors. Cigarette smoking, with the attendant hypoxia, is a probable
      contributing environmental factor. It seems likely that few clefts involve single
      major genes. In most cases, the pathogenesis appears to involve inadequate
      contact and/or fusion of the facial prominences or palatal shelves. Specific
      mutations in genes for different FGF receptor molecules have been identified for
      achondroplasia and Crouzon's syndrome, and in a regulatory gene (Msx2) for one
      type of craniosynostosis.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7632868
TI  - [Measurement and analysis of monophasic action potentials using fractally coated
      electrodes--I].
AB  - The monophasic action potential (MAP) contains a wealth of information about the
      stat of the myocardium, which makes it very useful for numerous diagnostic and
      therapeutic applications in patients with heart disease. The silver-silver
      chloride electrodes which are currently used for the measurement of MAP have poor
      long-term stability in contact with biological tissue. This study was therefore
      undertaken with the aim of investigating the electrochemical behaviour of
      fractally coated leads in terms of their signal-detection performance. Experience
      gained with these leads in cardiac pacemakers has already demonstrated the long
      term stability and biocompatibility of the fractally coated leads. Present
      results show that, due to their large electrochemically active surface area,
      fractally coated leads have a very low impedance over a wide frequency range. The
      negligible polarization artifact of these leads permits the measurement of
      cardiac potentials immediately after a stimulus. Fractally coated leads are thus
      highly suitable for the measurement of MAP, and have clear advantages over
      Ag/AgCl electrodes. The second part of this study reports on the results of MAP
      measurements using fractally coated leads.

PMID- 7632869
TI  - [Measurement and analysis of monophasic action potentials using fractally coated
      electrodes--II].
AB  - The monophasic action potential (MAP) represents a summed signal formed by
      overlapping action potentials of myocardial cells close to the tip of the lead.
      Analysis of the MAP therefore provides detailed information about the
      electrophysiological effects of autonomous nervous and pharmacological influences
      on the myocardium, for example adrenergic or cholinergic stimulation of the
      heart. All known MAP recordings were obtained with Ag/AgCl electrodes, which,
      thanks to their low polarization properties, ensure reliable MAP measurement.
      Owing to their toxicity and inadequate long-term stability, however, Ag/AgCl
      electrodes cannot be implanted. With the aim of making MAP measurement available
      for implantable devices, fractally coated leads were therefore developed. The aim
      of the present study was to evaluate the in vivo measurement of fractally coated
      leads which are characterized by negligible polarization, low impedance over a
      wide frequency range, high biocompatibility and good long-term stability. In
      addition, as a result of their extremely high Helmholtz capacities (up to 50
      mF/cm2), fractally coated leads permit stimulation and virtually undisturbed
      recording of MAP with the same pair of electrodes. For the evaluation of MAP
      measurements with fractally coated leads, a quadrupolar catheter enabling
      simultaneous MAP recordings with 2 Ag/AgCl electrodes and 2 fractally coated
      leads was devised. The stimulation pulses were always applied via the fractally
      coated leads. With both types of electrode, with spontaneous excitation and
      stimulation, the well-known MAP morphology, with amplitudes of between 10 and 25
      mV in the ventricle, and between 5 and 10 mV in the atrium, was seen.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7632870
TI  - A simulation study on magnetic source imaging with a realistic model of the
      entire human heart.
AB  - A computer model study on magnetic source imaging from magnetocardiographic data
      is presented using a cellular automaton model of the entire human heart in the so
      called forward problem. A homogeneous boundary element (BE) torso is built up
      from real magnetic resonance imaging (MRI) cross-sections. The heart model, which
      has a realistic anatomical shape, is positioned inside the BE torso. In the
      forward problem the spread of excitation is simulated by applying a modified
      Huygen's propagation principle. The magnetocardiogram (MCG) and electrocardiogram
      (ECG) can then be computed following the bidomain theory. From the simulated MCG
      data, pseudo primary current dipole (PPCD) estimation within the electrically
      active tissue is performed. The reconstruction space is defined as a surface in
      the middle of the atrial and ventricular myocardium and septum. The observation
      space consists of two mutually perpendicular planes closely above the torso
      surface on the frontal and the left lateral side, respectively. An iterative
      minimum-norm approach is applied in order to reconstruct PPCD distributions. The
      errors in PPCD estimation arising from noisy data and regularization algorithms
      are investigated in more detail.

PMID- 7632871
TI  - [Use of voxel-oriented femur models for stress analysis. Generation, calculation
      and validation of CT-based FEM models].
AB  - A means of interfacing computed tomography with the finite element method for the
      analysis of stress distribution in human femurs is described. With the aid of
      data transfer and image processing programs, three-dimensional voxel models of
      four macerated and a fresh-frozen cadaveric femur were generated from CT data
      sets. The underlying basic principle is direct generation of model elements from
      one or more adjacent CT-voxels, which are characterised by their coordinates and
      local absorption coefficients. A new algorithm was used for smoothing the edges
      of the model. All the models were analysed with respect to their stress
      distribution under different load situations, and the results were compared with
      the data of a parallel study utilizing the strain-gauge technique. Using the
      method of linear regression, a high correlation (coefficient of determination r2:
      0.80-0.91) was found between the calculated and experimentally measured principal
      stresses at the surface of the bones.

PMID- 7632872
TI  - On the molecular origins of thermal noise in vertebrate and invertebrate
      photoreceptors.
AB  - Retinal photoreceptors generate discrete electrical events in the dark
      indistinguishable from those evoked by light and the resulting dark signals limit
      visual sensitivity at low levels of illumination. The random spontaneous events
      are strongly temperature dependent and in both vertebrate and invertebrate
      photoreceptors require activation energies usually in the range of 23 to 28 kcal
      mol-1. Recent molecular orbital studies and pH experiments on horseshoe crabs
      (Limulus) suggest that the thermal isomerization of a relatively unstable form of
      rhodopsin, one in which the Schiff-base linkage between the chromophore and
      protein is unprotonated, is responsible for thermal noise. This mechanism is
      examined in detail and compared to other literature models for photoreceptor
      noise. We conclude that this two-step process is likely to be the principal
      source of noise in all vertebrate and invertebrate photoreceptors. This model
      predicts that the rate of photoreceptor noise will scale in proportion to 10- xi,
      where xi is the pKa of the Schiff base proton on the retinyl chromophore. Nature
      minimizes photoreceptor noise by selecting a binding site geometry which shifts
      the pKa of the Schiff base proton to > 16, a value significantly larger than the
      pKa of the chromophore in bacteriorhodopsin (pKa approximately 13) or model
      protonated Schiff bases in solution (pKa approximately 7).

PMID- 7632873
TI  - Alpha-helix formation by peptides of defined sequence.
AB  - The factors controlling alpha-helix formation in water by peptides of defined
      sequence are beginning to be understood. The field is close to the point where
      the extent of helix formation can be predicted for peptides of any sequence. Our
      own approach to the problem, and the main results obtained by following this
      approach, are summarized below. The chief reason for studying alpha-helix
      formation by peptides is to understand precisely and in detail one part of the
      protein folding problem. Questions about peptide helix formation can be answered
      at a fundamental level, in terms of the physico-chemical mechanisms involved.

PMID- 7632874
TI  - Bacteriorhodopsin: the mechanism of 2D-array formation and the structure of
      retinal in the protein.
AB  - Bacteriorhodopsin, the light driven proton pump of the extreme halophilic
      bacterium H. salinarium, is an integral membrane protein (M(r) ca. 26000) which
      forms 2D arrays in the purple membrane of the bacterium. It is this feature which
      has permitted the use of electron diffraction methods to resolve the protein
      structure to some degree of atomic detail, although the prosthetic group has not
      been fully resolved. However, the features which induce the protein to form these
      arrays have not been previously clarified. We have now shown that the protein
      array formation is driven by specific interaction of the protein with the charged
      phospholipid, phosphatidyl glycerol phosphate (or the sulphate derivative), a
      major (ca. 60%) lipid of the bacterial host membrane. In addition, in an effort
      to provide further structural information about the chromophore, retinal, of this
      protein, the orientation of the individual methyl groups of retinal have been
      determined from solid state deuterium NMR studies of the deuterated chromophore
      when in the protein binding site. This approach to structural resolution of the
      prosthetic group is ab initio, agrees with other studies on the chromophore and
      resolves new features of the bound retinal to a high degree (+/- 2 degrees) of
      precision. Here, these two studies on this integral membrane protein will be
      reviewed.

PMID- 7632875
TI  - Energy, control and DNA structure in the living cell.
AB  - Maintenance (let alone growth) of the highly ordered living cell is only possible
      through the continuous input of free energy. Coupling of energetically downhill
      processes (such as catabolic reactions) to uphill processes is essential to
      provide this free energy and is catalyzed by enzymes either directly or via
      "storage" in an intermediate high energy form, i.e., high ATP/ADP ratio or H+ ion
      gradient. Although maintenance of a sufficiently high ATP/ADP ratio is essential
      to overcome the thermodynamic burden of uphill processes, it is not clear to what
      degree enzymes that control this ratio also control cell physiology. Indeed, in
      the living cell homeostatic control mechanisms might exist for the free-energy
      transduction pathways so as to prevent perturbation of cellular function when the
      Gibbs energy supply is compromised. This presentation addresses the extent to
      which the intracellular ATP level is involved in the control of cell physiology,
      how the elaborate control of cell function may be analyzed theoretically and
      quantitatively, and if this can be utilized selectively to affect certain cell
      types.

PMID- 7632876
TI  - The alpha-helix as seen from the protein tertiary structure: a 3-D structural
      classification.
AB  - Helices are selected from globular protein structures defined at high resolution
      by X-ray analysis. We cluster alpha-helices in two ways: according to their
      position in the tertiary structure by considering patterns of solvent
      inaccessible residues and according to the arc of the solvent inaccessible face.
      For each class of helices we have defined propensities for amino acids at each
      position; these can be used to calculate templates for recognition of a member of
      that class. The analysis provides a basis for the prediction of alpha-helices and
      estimation of their approximate position in a protein tertiary structure. It also
      provides an approach to estimating the probability of finding amino acid
      sequences as helices in solution and in a folded protein, thus indicating those
      helices that might be involved in nucleation of protein folding.

PMID- 7632877
TI  - Crystallography of ribosomes: attempts at decorating the ribosomal surface.
AB  - Crystals of various ribosomal particles, diffracting best to 2.9 A resolution
      were grown. Crystallographic data were collected from shock frozen crystals with
      intense synchrotron radiation at cryo temperature. For obtaining phase
      information, monofunctional reagents were prepared from an undecagold and a
      tetrairidium cluster, by attaching to them chemically reactive handles, specific
      for sulfhydryl moieties. Heavy-atom derivatives were prepared by a specific and
      quantitative binding of the undecagold cluster to an exposed sulfhydryl prior to
      the crystallization. To create potential binding sites on the halophilic and
      thermophilic ribosomal particles, which yield our best and most interesting
      crystals, exposed reactive moieties were inserted, using genetic and chemical
      procedures. In order to choose the appropriate locations for these insertions,
      the surfaces of the ribosomal particles were mapped by direct chemical
      determination of exposed amino and sulfhydryl groups.

PMID- 7632878
TI  - Flexing and folding double helical DNA.
AB  - DNA base sequence, once thought to be interesting only as a carrier of the
      genetic blueprint, is now recognized as playing a structural role in modulating
      the biological activity of genes. Primary sequences of nucleic acid bases
      describe real three-dimensional structures with properties reflecting those
      structures. Moreover, the structures are base sequence dependent with individual
      residues adopting characteristic spatial forms. As a consequence, the double
      helix can fold into tertiary arrangements, although the deformation is much more
      gradual and spread over a larger molecular scale than in proteins. As part of an
      effort to understand how local structural irregularities are translated at the
      macromolecular level in DNA and recognized by proteins, a series of calculations
      probing the structure and properties of the double helix have been performed. By
      combining several computational techniques, complementary information as well as
      a series of built-in checks and balances for assessing the significance of the
      findings are obtained. The known sequence dependent bending, twisting, and
      translation of simple dimeric fragments have been incorporated into computer
      models of long open DNAs of varying length and chemical composition as well as in
      closed double helical circles and loops. The extent to which the double helix can
      be forced to bend and twist is monitored with newly parameterized base sequence
      dependent elastic energy potentials based on the observed configurations of
      adjacent base pairs in the B-DNA crystallographic literature.

PMID- 7632879
TI  - Static contributions to the persistence length of DNA and dynamic contributions
      to DNA curvature.
AB  - Long molecules of DNA have the statistical properties of a worm-like coil.
      Deviations from linearity occur both because of small dynamic bends induced by
      thermal motion and from a random distribution of static bends. The latter
      originate in the different conformations of each of the possible base pair
      sequences. In this paper a statistical theory of the persistence length of DNA is
      developed which includes both static and dynamic effects for each base pair
      sequence, as well as the sequence-dependent correlations of bending angles. The
      result applies to a generic DNA, i.e., the average over an ensemble of all
      possible sequences. The theory is also applied to the generation of the average
      properties of curved DNAs by an analytic method that includes dynamic averaging
      as well as correlated bends. These results provide information which supplements
      that obtained by others using Monte Carlo methods. The additivity relation 1/P =
      1/P(S) + 1/P(d) proposed by Trifonov et al., where P is the persistence length
      and P(S) and P(d) are the persistence lengths arising from purely static and
      dynamic effects, respectively, has been verified to be accurate to better than
      0.5%. This is true for both a simplified model and one that includes a complete
      set of static bends at all base pair sequences.

PMID- 7632880
TI  - Peptides in membranes: helicity and hydrophobicity.
AB  - Synthetic model membrane-interactive peptides--both of natural and designed
      sequence--have become convenient and systematic tools for determination of how
      the membrane-spanning segments within integral membrane proteins confer protein
      structure and biology. Conformational studies on these peptides demonstrate that
      the alpha-helix is the natural choice of conformation for a peptide segment in a
      membrane, and that a helical conformation will arise "automatically" in a peptide
      above a threshold hydrophobicity that allows it to associate stably with the
      membrane. Environmental and sequential contexts thus impart conformational
      versatility to many of the amino acids, thereby providing a mechanism for
      producing the diverse structural and functional properties of proteins.

PMID- 7632881
TI  - Mechanisms for the modulation of membrane bilayer properties by amphipathic
      helical peptides.
AB  - The amphipathic helix, in which hydrophobic and hydrophilic residues are grouped
      on opposing faces, is a structural motif found in many peptides and proteins that
      bind to membranes. One of the physical properties of membranes that can be
      altered by the binding of amphipathic helices is membrane monolayer curvature
      strain. Class A amphipathic helices, which are present in exchangeable plasma
      lipoproteins, can stabilize membranes by reducing negative monolayer curvature
      strain; proline-punctuated class A amphipathic helical segments are particularly
      effective in this regard. This property is suggested to be associated with some
      of the beneficial biological effects of this protein. On the other hand, lytic
      amphipathic helical peptides can act by increasing negative curvature strain or
      by forming pores composed of helical clusters. Thus, different amphipathic
      helical peptides can be membrane stabilizing or be lytic to membranes, depending
      on the structural motif of the helix, which in turn determines the nature of its
      association with membranes. Features of these peptides that are responsible for
      their specific properties are discussed.

PMID- 7632882
TI  - Corpus callosum and brain volume in women and men.
AB  - Using high-resolution in vivo magnetic resonance morphometry we measured the
      midsagittal area of the corpus callosum and total forebrain volume in 120 healthy
      young adults (mean age (+/- s.d.) 25.7 +/- 4.7 years). The forebrain volume
      adjusted size of the corpus callosum was larger in women than in men (32 mm2 mean
      difference; p = 0.011). Handedness had no effect in this measurement. The
      morphometric data confirm a gender difference in cerebral structural
      organization.

PMID- 7632883
TI  - Calcium signal prolongation in sensory neurones of mice with experimental
      diabetes.
AB  - Depolarization-induced Ca2+ transients were studied in dorsal root ganglion
      neurones of different size (large, 30-45 microns; small, 18-25 microns in
      diameter) from normal and diabetic mice. Whereas in large neurones no definite
      changes in the amplitude and time course of the transients were observed, in
      small neurones the decay of transient became substantially prolonged during
      streptozotocin-induced and spontaneously occurring diabetes. As small and large
      neurones differ substantially in their mechanisms of Ca2+ transient termination,
      we conclude that the prolongation of Ca2+ transients, probably induced by chronic
      hyperglycaemia, is specific only for small sensory neurones (transmitting mostly
      nociceptive signals) and may be a cause of the increased pain sensitivity often
      accompanying this disease.

PMID- 7632884
TI  - Neuronal activity of primate putamen during categorical perception of
      somaesthetic stimuli.
AB  - We have studied neuronal activity in the putamen of two monkeys trained to
      discriminate the speed of moving tactile stimuli. Animals pressed one of two
      target switches to indicate whether the speed of the probe across the skin was
      low or high. The activity of single neurones was recorded in the putamen
      ipsilateral to the glabrous skin of the stimulated hand and contralateral to the
      responding arm. During the task, we recorded neurones in the putamen that showed
      responses confined exclusively to the stimulus period of all speeds. A second
      class of putamen neurones responded during the stimulus period but continued
      discharging during the reaction and movement time period. None of these two
      classes of putamen neurones discharged when the same set of stimuli were
      delivered passively. A third class of putamen neurones responded differentially
      in the discrimination task and predicted whether the speed of the stimulus was
      low or high. A number of these neurones, which responded differentially during
      the categorization task, were tested in a light instruction task. This tested the
      possibility that these differential responses were associated with the intention
      to move the arm to one of the two target switches. Few neurones responded in this
      situation. These results indicate that the putamen, in addition to its role in
      motor regulation, is also involved in higher order aspects of sensory-motor
      behaviour and in the sensory decision process in this learned somaesthetic task.

PMID- 7632885
TI  - Interleukin 2 suppresses afferent sensory transmission in the primary
      somatosensory cortex.
AB  - The effect of topical application of interleukin 2 (IL-2) on afferent sensory
      transmission to the neurones in the primary somatosensory (SI) cortex was
      determined quantitatively in anaesthetized rats. IL-2 (0.1, 1.0, 5.0 units)
      significantly suppressed afferent sensory transmission in SI cortical neurones (n
      = 19) in a dose-dependent manner. IL-2-induced suppression fully recovered by 60
      min after drug. In control experiments, saline solution containing 0.2% bovine
      serum albumin, used as a vehicle, did not affect afferent sensory transmission.
      Our results suggest that IL-2 and its receptor present in the SI cortex may be
      involved in the processing of afferent sensory information.

PMID- 7632886
TI  - Poststimulus afterdischarges of spinal WDR and NS units in rats with chronic
      nerve constriction.
AB  - Forty pairs of wide dynamic range (WDR) and nociceptive specific (NS) neurones
      were simultaneously recorded in the dorsal horn of rats with chronic constriction
      injury (CCI) of the sciatic nerve. The responses to noxious mechanical
      stimulation were analysed and the afterdischarges were compared in the two
      neuronal populations. The number of neurones presenting an afterdischarge was
      higher in WDR than in NS population. Furthermore afterdischarges had
      significantly longer duration and greater magnitude with slower time course
      decays in WDR than in NS neurones. Given the role that afterdischarge may have in
      the prolonged transmission of nociceptive information, the possibility that WDR
      neurones could give a major contribute to the abnormal processing of noxious
      signals in CCI rats is proposed.

PMID- 7632887
TI  - Immunohistochemical localization of delta- and mu-opioid receptors in primate
      spinal cord.
AB  - Immunofluorescent techniques were used to examine the distribution of delta- and
      mu-opioid receptor-like immunoreactivity (ir) in primate spinal cord. At every
      segmental level examined, opioid receptor-ir formed a dense plexus of small
      profiles within the superficial dorsal horn. delta-Opioid receptor-ir was found
      in laminae I and II, whereas mu-opioid receptor-ir was confined mostly to lamina
      II. The distribution of opioid receptors within the superficial dorsal horn is
      appropriate for a localization to the central terminals of thinly myelinated and
      unmyelinated sensory neurons. Differences in the distribution of the delta- and
      mu-opioid receptors may reflect the presence of these two opioid receptor types
      on different functional classes of afferent neurons, or they may relate to
      differences in presynaptic and postsynaptic localization within the spinal gray
      matter.

PMID- 7632888
TI  - Neurones and glial cells of the mouse sciatic nerve undergo apoptosis after
      injury in vivo and in vitro.
AB  - Analogous to the death of developing neurones deprived of trophic factors, nerve
      injury in adult life could lead to nerve cell death by apoptosis. Here the
      occurrence of apoptotic mouse sciatic sensory neurones after injury was
      investigated by nick-labelling DNA breaks. A small proportion of the neurones
      reliably became apoptotic after injury in vivo. The response was strongly
      amplified when the nerves were injured in vitro, where Ca(2+)-chelation and
      protein synthesis inhibition were effective in inhibiting apoptosis. In addition
      to nerve cells, both Schwann cells and satellite cells became apoptotic after
      injury. Apoptosis in cultured mouse sciatic nerves appears advantageous for the
      identification of survival factors acting on adult peripheral neurones.

PMID- 7632889
TI  - Striatal dopamine participates in glutamate-induced hydroxyl radical generation.
AB  - Using a microdialysis technique we showed that the exposure of the rat striatum
      to glutamate yields hydroxyl radicals and results in striatal damage. We
      postulated that dopamine release is enhanced by glutamate perfusion and that the
      enzymatic metabolism of dopamine may account for this hydroxyl radical formation.
      The inhibition of monoamine oxidases by i.p. co-administration of clorgy-line and
      deprenyl reduced hydroxyl radical production induced by glutamate perfusion, but
      significantly increased the striatal damage. Our results suggest that the
      enzymatic metabolism of dopamine participates in glutamate-induced hydroxyl
      radical generation but that other by-products of dopamine may be responsible for
      the aggravation of the striatal injury.

PMID- 7632890
TI  - Action of argiotoxin636 on N-methyl-D-aspartate channels in cerebellar cells.
AB  - We investigated the mode of action of argiotoxin636 on isolated N-methyl-D
      aspartate (NMDA) receptor channels in cultured cerebellar granule cells. We found
      that the toxin blocks NMDA channels by decreasing their opening probability and
      by inducing a flickering activity, in a voltage-dependent manner. Our results
      indicate that argiotoxin636 acts as an open-channel blocker and might therefore
      be a useful tool for studying the structure of glutamate-gated channels.

PMID- 7632891
TI  - Endogenous histamine induces c-fos expression within paraventricular and
      supraoptic nuclei.
AB  - Thioperamide, an H3-receptor antagonist that enhances endogenous histamine
      release, induced c-fos mRNA expression and Fos-like immunoreactivity in
      magnocellular neurones of rat supraoptic and paraventricular nuclei. This
      response was prevented as a result of blockade of the H1 receptor, indicating
      that endogenous histamine is able to activate these magnocellular neurones via
      stimulation of this receptor.

PMID- 7632892
TI  - Human muscle macrophages express beta-amyloid precursor and prion proteins and
      their mRNAs.
AB  - Well-characterized antibodies against beta-amyloid precursor protein (beta APP)
      and prion protein (PrP), and specific cRNA probes, were used to localize beta APP
      and PrP and their mRNAs in human muscle macrophages. Macrophages present in
      muscle biopsies of 51 patients with various neuromuscular disorders showed
      accumulation of beta APP and PrP, and strongly expressed beta APP and PrP mRNAs.
      These were present in all muscle macrophages unrelated to their localization
      within the muscle tissue or diagnosis. Our study provides the first demonstration
      that human muscle resident macrophages synthesize and accumulate beta APP and
      PrP. We suggest that those proteins play a role in biology of muscle macrophages,
      including their participation in inflammatory and immune responses.

PMID- 7632894
TI  - In situ evidence for DNA fragmentation in Huntington's disease striatum and
      Alzheimer's disease temporal lobes.
AB  - To test the hypothesis that apoptosis is involved in human brain
      neurodegenerative disorders, we investigated whether DNA fragmentation occurs in
      Alzheimer's disease (AD). Huntington's disease (HD) and Parkinson's disease, as
      well as in temporal lobe epilepsy, using neurologically normal post-mortem human
      brain tissue as a control. Using in situ end labelling of DNA, we found evidence
      of DNA fragmentation in cells in temporal cortex and hippocampus from patients
      with AD and in striatum from those with HD. In contrast, only scattered DNA
      fragmentation positive cells were detected in the pial surfaces of some of the
      neurologically normal human brains. Thus, cells in the HD striatum and AD
      temporal cortex exhibited DNA fragmentation, suggesting that apoptosis may be
      involved in these disorders.

PMID- 7632893
TI  - Up-regulation of PKA RI alpha subunit mRNA in rat skeletal muscle after nerve
      injury.
AB  - Localization of all subunits of cAMP dependent protein kinase (PKA) mRNAs and
      their changes of expression after denervation were examined in rat tongue
      skeletal muscle by in situ hybridization histochemistry. Among all PKA subunits
      only RI alpha subunit mRNA was detected in the skeletal muscle, whereas positive
      signal of all subunits mRNA were observed in some haematocytes or lymphocytes
      within the tongue tissue. The RI alpha mRNA was distributed in a restricted area
      near the endplate. The mRNA level was substantially induced by the hypoglossal
      nerve transection, suggesting that the up-regulation of RI alpha mRNA leading to
      the down-regulation of PKA activity may contribute to some intracellular
      signalling modulation or to muscle specific gene transcription after the
      denervation.

PMID- 7632895
TI  - Agonist action of (RS)-alpha-methyl-4-carboxyphenylglycine (MCPG) in the
      amygdala.
AB  - Glutamatergic excitatory postsynaptic potentials (EPSPs) in the basolateral
      amygdala (BLA) are reduced in amplitude following agonist activation of
      presynaptic metabotropic glutamate receptors (mGluR). In this study, the effect
      of a presumed mGluR antagonist, (RS)-alpha-methyl-4-carboxyphenylglycine (MCPG),
      was investigated on the EPSP recorded intracellularly in BLA neurons. Superfusion
      of MCPG (500 microM) significantly reduced the amplitude of evoked EPSPs. In the
      presence of MCPG, postsynaptic responses to alpha-amino-3-hydroxy-5-methyl-4
      isoxazoleproprionic acid (AMPA, 1 microM) were unaltered while responses to N
      methyl-D-aspartate (NMDA, 3-5 microM) were potentiated. These data suggest that
      the MCPG-induced reduction of EPSP amplitude is due to a mGluR agonist action at
      a presynaptic mGluR 'autoreceptor'.

PMID- 7632896
TI  - Nerve growth factor in Alzheimer's disease: defective retrograde transport to
      nucleus basalis.
AB  - NGF immunohistochemistry was combined with quantitative optical densitometry to
      evaluate whether retrogradely transported NGF is altered within cholinergic basal
      forebrain (CBF) neurons in Alzheimer's disease (AD). In normal aged humans,
      almost all CBF neurons stained for NGF. Although fewer in total number, remaining
      CBF perikarya in AD displayed diminished (32%) or undetectable NGF
      immunoreactivity. Based upon these data we hypothesize that there is a defect in
      retrograde transport of NGF in AD which may be due to a abnormal production
      and/or utilization of the trk receptor. This defect may be a primary event
      mediating the degeneration of CBF neurons in AD.

PMID- 7632897
TI  - Behavioural assessment of endothelin-1 induced middle cerebral artery occlusion
      in the rat.
AB  - The behavioural effects of unilateral middle cerebral artery occlusion (MCAO)
      induced by perivascular injection of endothelin, and a unilateral excitotoxic
      lesion of the striatum, were explored using the staircase test of skilled paw
      reaching in the rat. A profound bilateral impairment in pellet recovery, with a
      concomitant increase in pellet displacement, was observed in the MCAO group. By
      contrast the striatal lesion group exhibited a primarily contralateral
      impairment. The findings provide both further insight into the control of
      unilateral motor function and a reliable behavioural endpoint for the assessment
      of experimental stroke.

PMID- 7632898
TI  - Peptidergic delineations of nucleus interface reveal a sex difference in volume.
AB  - Nucleus interface (Nif) is a song bird vocal control nucleus located in the
      neostriatum. In zebra finches (Taeniopygia guttata), high densities of fibers
      immunoreactive for the vasoactive intestinal polypeptide (VIP) and methionine
      enkephalin (ENK) define the boundaries of this nucleus. The volume of Nif
      measured using this pattern of peptidergic immunoreactivity was greater in males
      than in females. This difference was also found in gonadectomized, testosterone
      treated birds that had similar levels of circulating steroids, suggesting that it
      is organizational in nature. These data show that Nif may form part of the neural
      substrate underlying sex differences in song behavior. They also provide further
      evidence that VIP and ENK may play a role in the activation of bird song.

PMID- 7632899
TI  - Abrupt unilateral deafness modifies function of human auditory pathways.
AB  - We studied nine patients with unilateral abrupt deafness caused by acoustic
      neuroma surgery. Cortical responses to tones delivered to the intact ear were
      recorded postoperatively with a 122-channel whole-scalp neuromagnetometer. In
      three patients, followed for 12 months with 2-4 measurements, evoked responses
      originating in the auditory cortices were weak and delayed one month after the
      operation in both hemispheres. During the follow-up, the amplitudes reached the
      control level. No response abnormalities were found in patients who were studied
      1.5-4.5 years after the operation. Our findings suggest that abrupt unilateral
      deafness causes immediate changes in the function of auditory pathways of adult
      humans and that reorganization takes place within 1 year.

PMID- 7632900
TI  - Coordinate expression of vesicular acetylcholine transporter and choline
      acetyltransferase in sympathetic superior cervical neurones.
AB  - The neurotransmitter acetylcholine is synthesized by choline acetyltransferase
      (ChAT) and transported into synaptic vesicles by the vesicular acetylcholine
      transporter (VAChT). Recently it has been reported that the entire coding region
      of VAChT mRNA is located in the first intron of the ChAT gene. In this study,
      ChAT and VAChT mRNAs were analysed in cultured sympathetic neurones. Cholinergic
      differentiation factor/leukaemia inhibitory factor and ciliary neurotrophic
      factor induced strong expression of ChAT and VAChT mRNAs in parallel. RT-PCR
      analysis of ChAT mRNAs revealed that five types of ChAT transcripts which
      differed in the 5' non coding regions were increased. RT-PCR analysis of VAChT
      mRNA indicated that the cytokines induced only VAChT mRNA species which did not
      contain the R-exon, and not those containing the R-exon. The results indicate
      that ChAT and VAChT expressions are coordinately but differentially regulated in
      cultured sympathetic neurones.

PMID- 7632903
TI  - Descending efferent connections of the sub-pallidal areas in the cat: projections
      to the lateral habenula.
AB  - The descending efferent connections of the sub-pallidal areas to the lateral
      habenula were investigated in the cat using Phaseolus vulgaris leucoagglutinin
      (PHA-L) as an anterograde tracer. Several injections of PHA-L were made in
      various regions of the feline sub-pallidal regions. Subsequently, the
      distribution of anterogradely labelled fibres in the lateral habenula was
      charted. PHA-L injections into the rostral part of the sub-pallidal regions
      resulted in a limited number of labelled fibres in the lateral habenula, while
      PHA-L injections into the caudal regions of the sub-pallidum resulted in an
      extensive distribution of anterogradely labelled fibres in this area. Thus, the
      lateral habenula is an important output structure of the sub-pallidal areas in
      the cat.

PMID- 7632902
TI  - Differential localization of heme oxygenase and NADPH-diaphorase in spinal cord
      neurons.
AB  - Western blot analysis using several antibodies showed that rat spinal cord
      contained abundant immunostainable heme oxygenase-2 (HO-2) and barely detectable
      levels of heme oxygenase-1 (HO-1). Anti-HO-2 antibody stained large anterior horn
      motoneurones and numerous smaller neurons throughout spinal cord gray matter
      including the dorsal root entry zone. HO-2+ astrocytes were not evident in gray
      matter although their presence cannot be ruled out. The distribution of HO-2+
      neurons was compared with the distribution of cells containing NADPH-diaphorase
      (NADPH-d) activity, a marker for nitric oxide synthase. NADPH-d activity was
      restricted to far fewer neurons, many of which were close to the central canal
      and dorsal root entry zone.

PMID- 7632901
TI  - N-terminal cysteines essential for Golgi sorting of B-50 (GAP-43) in PC12 cells.
AB  - We have examined the subcellular distribution of the growth-associated protein B
      50 (GAP-43) in pheochromocytoma (PC12) cells, using confocal microscopy.
      Proliferating PC12 cells contained very low levels of B-50 in the cytosol.
      Enhanced expression of B-50 in these cells, evoked by either nerve growth factor
      (NGF) treatment or transient transfection with rat B-50 cDNA, led to Golgi
      sorting and membrane targeting of the B-50 protein. Site directed mutagenesis of
      Cys3Cys4 to Ser3Gly4 in B-50 resulted in a cytosolic distribution. We conclude
      that Cys3, and Cys4 are essential for accumulation of B-50 both at the plasma
      membrane and in the Golgi apparatus of PC12 cells.

PMID- 7632904
TI  - Supporting cells in isolated sensory epithelia of avian utricles proliferate in
      serum-free culture.
AB  - Sheets of sensory epithelia were isolated from the utricles of chicks and
      cultured in serum-free media and in media that contained serum. The proliferation
      of epithelial supporting cells was assayed using the mitotic tracer
      bromodeoxyuridine. Similar levels of supporting cell proliferation were observed
      in epithelia maintained in serum-free and serum-containing media. The results
      suggest that the vestibular epithelia of birds contain whatever mitogens are
      necessary for the continued proliferation of epithelial supporting cells.

PMID- 7632906
TI  - Topographical reinnervation of the toad glutaeus muscle by axons of only one
      spinal nerve.
AB  - The toad glutaeus muscle is innervated by axons from two spinal nerves. Following
      regeneration from nerve lesion, axonal reinnervation from both spinal nerves
      remains topographically selective. The aim of the present experiments was to
      determine whether axons from one spinal nerve (nerve 9) would topographically
      reinnervate the glutaeus muscle in the absence of innervation from the other
      spinal nerve (nerve 8). Glycogen depletion of single motor units showed that
      nerve 9 axons are topographically selective when reinnervating the muscle alone.
      The synapses formed are stronger in topographically correct locations even in the
      absence of nerve 8 innervation. The distinction between the territory innervated
      by rostral and caudal nerve 9 axons arises independently of the presence of nerve
      8 axons.

PMID- 7632907
TI  - Congruent unilateral impairments for real and imagined hand movements.
AB  - The chronometry of imagined and actual movements was investigated in a patient
      with a unilateral lesion of the motor cortex. Motor imagery generated highly
      accurate estimates of motor performance in a variety of situations, reflecting
      the hypokinesia of the contralesional hand. There were parallel increases in
      mental and actual movement times from proximal to distal limb segments. Bimanual
      movements adopted the slower speed of the impaired hand in both conditions.
      Imagined motor sequences to the beat of a metronome predicted the maximum speed
      reached in actual performance. Finally, visually guided pointing showed the same
      target-size effects in the imagery and movement conditions. The results are in
      agreement with the hypothesis that common cerebral motor representations are
      activated when imaging and planning voluntary movements.

PMID- 7632905
TI  - Cerebellar interpositus nucleus modulates neuronal activity of lateral
      hypothalamic area.
AB  - Effects of stimulating the cerebellar interpositus nucleus (IN) on the neuronal
      activity of lateral hypothalamic area (LHA) were first observed in the cat. The
      results showed that (1) IN stimulation could elicit inhibitory, excitatory,
      inhibitory-excitatory and excitatory-inhibitory responses from LHA neurones, with
      a majority of inhibitory responses (46.9%); (2) the responsive latencies of LHA
      neurones to IN stimulation ranged from 5 to 45 ms, while most (83.6%) showed a
      short latency of < 15 ms; (3) of 67 LHA neurones which responded to the IN
      stimulation, 42 (62.7%) cells were identified to be glucose-sensitive neurones.
      These results suggest that IN may be involved in the role of LHA modulating food
      intake behaviour, as well as other non-somatic functions.

PMID- 7632908
TI  - Molecular cloning of the cDNA encoding a stress-inducible protein phosphatase 1
      (PP1) catalytic subunit from French bean (Phaseolus vulgaris L.).
AB  - A cDNA showing high sequence similarity (> 70%) to plant protein phosphatase 1
      catalytic subunit variants from other species has been isolated from a cDNA
      library derived from mRNAs expressed in elicitor-treated suspension-cultured
      cells. The clone appears to be a near full-length 1431 bp with a 172 bp 5'
      untranslated region and a 317 bp 3'-untranslated region. The open reading frame,
      determined by sequence similarity, codes for a protein with predicted M(r) of
      35,552. Alternatively an ATG situated to the 5' end of the putative start site
      would increase the protein size by 6 amino acids. The mRNA for Pvpp1 was shown to
      be rapidly induced by elicitor treatment of suspension-cultured cells of French
      bean. The cloned cDNA represents one of the few examples of a gene product that
      is probably involved in dephosphorylation events arising after the initial
      responses to biotic stress.

PMID- 7632911
TI  - Characterisation of two tomato fruit-expressed cDNAs encoding xyloglucan endo
      transglycosylase.
AB  - Xyloglucan endo-transglycosylase (XET) catalyses the cleavage and concomitant
      transfer of one xyloglucan molecule to another. It is thought to be an important
      component of cell wall metabolism, particularly in expanding tissue and ripening
      fruits. The recently reported cloning of a cDNA encoding a seed-expressed XET
      from nasturtium [9] has enabled two XET-encoding cDNAs to be isolated from a
      tomato fruit (breaker stage) cDNA library. Their deduced amino acid sequences
      exhibit ca. 40% identity to nasturtium XET. One of the tomato cDNA clones (tXET
      B2) was over-expressed in Escherichia coli; following purification and refolding,
      the recombinant protein was shown to have XET activity, with no detectable
      hydrolytic activity. Southern hybridisation analysis suggests that these clones
      are members of a small multi-gene family encoding tomato XET. Ribonuclease
      protection assays show that transcripts protected by one of the clones (tXET-B1)
      are most abundant in pink fruit pericarp and were also detected in stems.

PMID- 7632909
TI  - Isolation and characterisation of cDNA clones representing the genes encoding the
      major tuber storage protein (dioscorin) of yam (Dioscorea cayenensis Lam.).
AB  - cDNA clones encoding dioscorins, the major tuber storage proteins (M(r) 32,000)
      of yam (Dioscorea cayenesis) have been isolated. Two classes of clone (A and B,
      based on hybrid release translation product sizes and nucleotide sequence
      differences) which are 84.1% similar in their protein coding regions, were
      identified. The protein encoded by the open reading frame of the class A cDNA
      insert is of M(r) 30,015. The difference in observed and calculated molecular
      mass might be attributed to glycosylation. Nucleotide sequencing and in vitro
      transcription/translation suggest that the class A dioscorin proteins are
      synthesised with signal peptides of 18 amino acid residues which are cleaved from
      the mature peptide. The class A and class B proteins are 69.6% similar with
      respect to each other, but show no sequence identity with other plant proteins or
      with the major tuber storage proteins of potato (patatin) or sweet potato
      (sporamin). Storage protein gene expression was restricted to developing tubers
      and was not induced by growth conditions known to induce expression of tuber
      storage protein genes in other plant species. The codon usage of the dioscorin
      genes suggests that the Dioscoreaceae are more closely related to dicotyledonous
      than to monocotyledonous plants.

PMID- 7632910
TI  - A novel stress-inducible metallothionein-like gene from rice.
AB  - A novel rice genomic sequence encoding coding segments homologous to other
      metallothionein-like genes was isolated from Oryza sativa genomic library. This
      sequence, hereby designated as rgMT (rice genomic metallothionein-like gene),
      consists of two exons and one intron. From the coding sequence, it is predicted
      that rgMT encodes one protein of 74 amino acids. Differential expression of rgMT
      in rice plants was observed as mature transcripts were more abundant in roots
      than in leaves and sheaths. Under different stress conditions, such as excess
      heavy metals and heat shock, expression of rgMT was significantly elevated. This
      was especially noticeable with 250 microM CuCl2 for 16 h, 40 degrees C heat for 2
      h and 0.06% DMSO for 1 h. Under sucrose starvation, rgMT transcripts also
      increased with time up to 72 h. During recovery from sucrose starvation, the
      transcripts declined slightly within 12 h of recovery. rgMT transcripts were also
      seen to have increased expression in senescent leaves. These results support the
      notion that rgMT is a stress-inducible gene in rice heretofore unreported.

PMID- 7632912
TI  - The nodule-specific VfENOD-GRP3 gene encoding a glycine-rich early nodulin is
      located on chromosome I of Vicia faba L. and is predominantly expressed in the
      interzone II-III of root nodules.
AB  - A nodule-specific cDNA was isolated from a Vicia faba L. nodule cDNA library.
      Since time course experiments revealed an early expression of this transcript in
      the nodule, this cDNA coded for an early nodulin and was designated VfENOD-GRP3.
      Based on tissue print hybridizations, we found a predominant expression of VfENOD
      GRP3 transcripts in the interzone II-III region of broad bean root nodules. The
      encoded early nodulin ENOD-GRP3 was characterized by an N-terminal signal peptide
      and a C-terminal domain displaying a glycine content of 31%. Sequence analysis of
      a genomic VfENOD-GRP3 clone revealed that the signal peptide and the glycine-rich
      domain were specified by two separate exons. Primer extension experiments
      identified two adjacent transcription start sites for VfENOD-GRP3 transcripts.
      The common nodulin sequences 'AAAGAT' and 'CTCTT' were present five and three
      times on both DNA strands of the putative VfENOD-GRP3 promoter, respectively.
      Additionally, three sequence motifs resembling organ-specific elements of the
      soybean lbc3 gene promoter and a sequence similar to the binding site 1 for the
      nodule trans-acting factor Nat2 were identified. From Southern blot data and from
      sequence analysis of genomic PCR fragments, the presence of a VfENOD-GRP3 gene
      family was inferred. By PCR experiments using sequence-specific primers and DNA
      of microisolated chromosomes as a template, this family was located on the long
      arm of chromosome I.

PMID- 7632913
TI  - High levels of ripening-specific reporter gene expression directed by tomato
      fruit polygalacturonase gene-flanking regions.
AB  - The 1.4 kb 5' polygalacturonase (PG) gene-flanking region has previously been
      demonstrated to direct ripening-specific chloramphenicol acetyl transferase (CAT)
      expression in transgenic tomato plants. The steady state level of CAT mRNA in
      these plants was estimated to be less than 1% of the endogenous PG mRNA. Further
      constructs containing larger PG gene-flanking regions were generated and tested
      for their ability to direct higher levels of reporter gene expression. A 4.8 kb
      5'-flanking region greatly increased levels of ripening-specific reporter gene
      activity, while a 1.8 kb 3' region was only shown to have a positive regulatory
      role in the presence of the extended 5' region. Transgenic plants containing the
      CAT gene flanked by both of these regions showed the same temporal pattern of
      accumulation of CAT and PG mRNA, and steady-state levels of the transgene mRNA
      were equivalent to 60% of the endogenous PG mRNA on a per gene basis. The
      proximal 150 bp of the PG promoter gave no detectable CAT activity. However, the
      distal 3.4 kb of the 4.8 kb 5' PG promoter was shown to confer high levels of
      ripening-specific gene expression when placed in either orientation upstream of
      the 150 bp minimal promoter. The DNA sequence of the 3.4 kb region revealed a 400
      bp imperfect reverse repeat, and sequences which showed similarity to
      functionally significant sequences from the ripening-related, ethylene-regulated
      tomato E8 and E4 gene promoters. The possible roles of the flanking regions in
      regulating PG gene expression are discussed.

PMID- 7632914
TI  - A transposon-like sequence with short terminal inverted repeats in the nuclear
      genome of Chlamydomonas reinhardtii.
AB  - A 1.2 kb DNA sequence, flanked by a potential seven base target-site duplication,
      was found inserted into a TOC1 transposable element from Chlamydomonas
      reinhardtii. The insertion sequence, named TOC2, is a member of a family of
      repeated DNA sequences that is present in all the C. reinhardtii strains tested.
      It resembles class II transposable elements: it possesses short 14 bp imperfect
      terminal repeats that begin AGGAGGGT, and sub-terminal direct repeats located
      within 250 bp of the termini. No large open reading frames were found. The
      terminal bases and length of target-site duplication are important in classifying
      transposable elements. On this basis TOC2 does not fall readily into existing
      families of class II transposable elements found in plants.

PMID- 7632915
TI  - Characterization of a Chlamydomonas reinhardtii gene encoding a protein of the
      DNA photolyase/blue light photoreceptor family.
AB  - The organization and nucleotide sequence of a gene from Chlamydomonas reinhardtii
      encoding a member of the DNA photolyase/blue light photoreceptor protein family
      is reported. A region of over 7 kb encompassing the gene was sequenced. Northern
      analysis detected a single 4.2 kb mRNA. The gene consists of eight exons and
      seven introns, and encodes a predicted protein of 867 amino acids. The first 500
      amino acids exhibit significant homology with previously sequenced DNA
      photolyases, showing the closest relationship to mustard (Sinapis alba)
      photolyase (43% identity). An even higher identity, 49%, is obtained when the
      Chlamydomonas gene product is compared to the putative blue-light photoreceptor
      (HY4) from Arabidopsis thaliana. Both the Chlamydomonas and the Arabidopsis
      proteins differ from the well characterized DNA photolyases in that they contain
      a carboxyl terminal extension of 367 and 181 amino acids, respectively. However,
      there is very little homology between the carboxyl terminal domains of the two
      proteins. A previously isolated Chlamydomonas mutant, phr1, which is deficient in
      DNA photolyase activity, especially in the nucleus, was shown by RFLP analysis
      not to be linked to the gene we have isolated. We propose this gene encodes a
      candidate Chlamydomonas blue light photoreceptor.

PMID- 7632917
TI  - Molecular cloning and characterization of six cDNAs expressed during glucose
      starvation in excised maize (Zea mays L.) root tips.
AB  - In order to isolate glucose-starvation-related cDNAs in maize (Zea mays L.) root
      tips, a cDNA library was constructed with poly(A)+ mRNA from 24 h starved root
      tips. After differential screening of the library, we isolated six different
      cDNAs (named pZSS2 and pZSS7) which were expressed during glucose starvation.
      Time course analysis revealed that maximum expression of five of these genes
      occurs 30 h after the onset of the starvation treatment. On the contrary, the
      expression of mRNAs corresponding to pZSS4 was maximal at an early stage of
      starvation and then dramatically decreased. The expression of this gene did not
      seem to be specific for glucose starvation. The pattern of induction of the genes
      corresponding to pZSS2, pZSS3, pZSS5, pZSS6 and pZSS7 revealed that non
      metabolizable sugars such as L-glucose and mannitol induce mRNA transcription
      similarly to glucose starvation. When D-glucose or any other metabolizable sugar
      was supplied, the level of transcripts was reduced. Nucleotide sequence analyses
      of the six cDNAs allowed identification of five of them by comparison with
      sequence data bases. The protein encoded by clone pZSS2 is analogous to a wound
      induced protein from barley. Clones pZSS4 to pZSS7 encode, respectively, a
      transmembrane protein, a cysteine protease, a metallothionein-like protein and a
      chymotrypsin/subtilisin-like protease inhibitor. Clone pZSS3 shares no
      significant homology with any known sequence.

PMID- 7632916
TI  - Expression of the rice Osgrp1 promoter-Gus reporter gene is specifically
      associated with cell elongation/expansion and differentiation.
AB  - To study the expression and regulation of a rice glycine-rich cell wall protein
      gene, Osgrp1, transgenic rice plants were regenerated that contain the Osgrp1
      promoter or its 5' deletions fused with the bacterial beta-glucuronidase (GUS)
      reporter gene. We report here a detailed histochemical analysis of the Osgrp1-Gus
      expression patterns in transgenic rice plants. In roots of transgenic rice
      plants, GUS expression was specifically located in cell elongation and
      differentiation regions, and no GUS expression was detectable in the apical
      meristem and the mature region. In shoots, GUS activity was expressed only in
      young leaves or in the growing basal parts of developing leaves, and little GUS
      activity was expressed in mature leaves or mature parts of developing leaves. In
      shoot apices, GUS activity was detected only in those leaf cells which were
      starting to expand and differentiate, and GUS expression was not detected in the
      apical meristem and the young meristematic leaf primordia. GUS activity was
      highly expressed in the young stem tissue, particularly in the developing
      vascular bundles and epidermis. Thus, the expression of the Osgrp1 gene is
      closely associated with cell elongation/expansion during the post-mitotic cell
      differentiation process. The Osgrp1-Gus gene was also expressed in response to
      wounding and down-regulated by water-stress conditions in the elongation region
      of roots. Promoter deletion analysis indicates that both positive and negative
      mechanisms are involved in regulating the specific expression patterns. We
      propose a simple model for the developmental regulation of the Osgrp1 gene
      expression.

PMID- 7632918
TI  - Chlamydomonas reinhardtii thioredoxins: structure of the genes coding for the
      chloroplastic m and cytosolic h isoforms; expression in Escherichia coli of the
      recombinant proteins, purification and biochemical properties.
AB  - Based on known amino acid sequences, probes have been generated by PCR and used
      for the subsequent isolation of cDNAs and genes coding for two thioredoxins (m
      and h) of Chlamydomonas reinhardtii. Thioredoxin m, a chloroplastic protein, is
      encoded as a preprotein of 140 amino acids (15,101 Da) containing a transit
      peptide of 34 amino acids with a very high content of Ala and Arg residues. The
      sequence for thioredoxin h codes for a 113 amino acid protein with a molecular
      mass of 11,817 Da and no signal sequence. The thioredoxin m gene contains a
      single intron and seems to be more archaic in structure than the thioredoxin h
      gene, which is split into 4 exons. The cDNA sequences encoding C. reinhardtii
      thioredoxins m and h have been integrated into the pET-3d expression vector,
      which permits efficient production of proteins in Escherichia coli cells. A high
      expression level of recombinant thioredoxins was obtained (up to 50 mg/l
      culture). This has allowed us to study the biochemical/biophysical properties of
      the two recombinant proteins. Interestingly, while the m-type thioredoxin was
      found to have characteristics very close to the ones of prokaryotic thioredoxins,
      the h-type thioredoxin was quite different with respect to its kinetic behaviour
      and, most strikingly, its heat denaturation properties.

PMID- 7632919
TI  - Ethylene-regulated expression of a carnation cysteine proteinase during flower
      petal senescence.
AB  - The senescence of carnation (Dianthus caryophyllus L.) flower petals is regulated
      by the phytohormone ethylene and is associated with considerable catabolic
      activity including the loss of protein. In this paper we present the molecular
      cloning of a cysteine proteinase and show that its expression is regulated by
      ethylene and associated with petal senescence. A 1600 bp cDNA was amplified by
      polymerase chain reaction using a 5'-specific primer and 3'-nonspecific primer
      designed to amplify a 1-aminocyclopropane-1-carboxylate synthase cDNA from
      reverse-transcribed stylar RNA. The nucleotide sequence of the cloned product
      (pDCCP1) was found to share significant homology to several cysteine proteinases
      rather than ACC synthase. A single open reading frame of 428 amino acids was
      shown to share significant homology with other plant cysteine proteinases
      including greater than 70% identity with a cysteine proteinase from Arabidopsis
      thaliana. Amino acids in the active site of cysteine proteinases were conserved
      in the pDCCP1 peptide. RNA gel blot analysis revealed that the expression of
      pDCCP1 increased substantially with the onset of ethylene production and
      senescence of petals. Increased pDCCP1 expression was also associated with
      ethylene production in other senescing floral organs including ovaries and
      styles. The pDCCP1 transcript accumulated in petals treated with exogenous
      ethylene within 3 h and treatment of flowers with 2,5-norbornadiene, an inhibitor
      of ethylene action, prevented the increase in pDCCP1 expression in petals. The
      temporal and spatial patterns of pDCCP1 expression suggests a role for cysteine
      proteinase in the loss of protein during floral senescence.

PMID- 7632920
TI  - cry IA(b) transcript formation in tobacco is inefficient.
AB  - Chimaeric PCaMV35Scry genes direct in tobacco mesophyll protoplasts mRNA levels
      of less than one transcript per cell. We provide evidence that this low
      cytoplasmic cry IA(b) mRNA level is not due to a rapid turnover but rather
      results from a marginal import flow of cry messenger into the cytoplasm. Run-on
      assays indicate that the frequency of transcription initiation is not limiting.
      However, the cry precursor mRNA carries at least three regions that are
      recognized as introns. The absence of high cytoplasmic levels of spliced cry
      mRNAs suggests that these mRNAs are unstable and/or not efficiently made. Point
      mutations in the 5' splice site of the most distal intron allows high
      accumulation levels of the full-length mRNA. This implies that the inefficient
      formation of full-size mRNA is a major cause of the low expression level of
      chimaeric cry IA(b) genes in tobacco.

PMID- 7632921
TI  - Peculiar properties of the PsaF photosystem I protein from the green alga
      Chlamydomonas reinhardtii: presequence independent import of the PsaF protein
      into both chloroplasts and mitochondria.
AB  - It has previously been shown that presequences of nuclear-encoded chloroplast
      proteins from the green alga Chlamydomonas reinhardtii contain a region that may
      form an amphiphilic alpha-helix, a structure characteristic of mitochondrial
      presequences. We have tested two precursors of chloroplast proteins (the PsaF and
      PsaK photosystem I subunits) from C. reinhardtii for the ability to be imported
      into spinach leaf mitochondria in vitro. Both precursors bound to spinach
      mitochondria. The PsaF protein was converted into a protease-protected form with
      high efficiency in a membrane potential-dependent manner, indicating that the
      protein had been imported, whereas the PsaK protein was not protease protected.
      The protease protection of PsaF was not inhibited by a synthetic peptide derived
      from the presequence of the N. plumbaginifolia mitochondrial F1 beta subunit.
      Furthermore, if the presequence of PsaF was truncated or deleted by in vitro
      mutagenesis, the protein was still protease-protected with approximately the same
      efficiency as the full-length precursor. These results indicate that PsaF can be
      imported by spinach mitochondria in a presequence-independent manner. However,
      even in the absence of the presequence, this process was membrane potential
      dependent. Interestingly, the presequence-truncated PsaF proteins were also
      protease-protected upon incubation with C. reinhardtii chloroplasts. Our results
      indicate that the C. reinhardtii chloroplast PsaF protein has peculiar properties
      and may be imported not only into chloroplasts but also into higher-plant
      mitochondria. This finding indicates that additional control mechanisms in the
      cytosol that are independent of the presequence are required to achieve sorting
      between chloroplasts and mitochondria in vivo.

PMID- 7632922
TI  - Dark induction and subcellular localization of the pathogenesis-related PRB-1b
      protein.
AB  - The PRB-1b gene codes for a basic-type pathogenesis-related protein of the PR-1
      family of tobacco. PRB-1b mRNA accumulation is induced in response to biotic and
      abiotic elicitors, such as TMV, ethylene, salicylic acid, alpha-amino butyric
      acid and darkness. In order to determine the location of elements that control
      dark-regulated PRB-1b gene expression, we tested promoter, transcribed regions
      and 3'-downstream regions of the gene for their ability to respond to dark
      induction in transgenic tobacco plants. An ethylene-inducible promoter region of
      863 bp was not able to confer dark induction to a beta-glucuronidase reporter
      gene, while a construct containing the transcribed region of the gene and 3'
      downstream sequences, driven by the cauliflower mosaic virus 35S promoter, was
      correctly dark-regulated. The results indicate that dark-induction of the PRB-1b
      gene can be controlled by 3'-downstream elements at the transcriptional level or
      by transcribed sequences at the post-transcriptional level. A circadian clock
      regulation of the PRB-1b gene was excluded, as fluctuations of PRB-1b transcript
      levels were not observed in plants placed in constant light or darkness.
      Subcellular localization of the PRB-1b protein was also determined, in tobacco
      protoplasts preparations and in cell cultures. The PRB-1b polypeptide was
      predominantly detected in protoplast vacuoles and was not secreted to the media
      in cell cultures. These results support an intracellular localization for the PRB
      1b protein, as reported for other basic-type components of the pathogenesis
      related proteins family.

PMID- 7632923
TI  - The Arabidopsis MADS-box gene AGL3 is widely expressed and encodes a sequence
      specific DNA-binding protein.
AB  - The Arabidopsis AGL3 gene was previously identified on the basis of sequence
      similarity to the floral homeotic gene AGAMOUS (AG), which encodes a protein with
      a conserved MADS domain that is also found in human and yeast transcription
      factors (SRF and MCM1, respectively). Analysis of newly isolated full-length cDNA
      clones as well as genomic clones indicates that AGL3 is indeed a MADS-box gene
      with a general intron-exon structure similar to other plant MADS-box genes.
      However, unlike the others, which are expressed specifically in flowers, AGL3 is
      expressed in all above-ground vegetative organs, as well as in flowers, but not
      in roots. Furthermore, since AGL3 is MADS-domain protein, it is likely that it is
      also a DNA-binding protein regulating transcription. To characterize AGL3 as a
      DNA-binding protein in vitro, we expressed the AGL3 protein in Escherichia coli,
      and characterized its DNA-binding properties. We show that AGL3 binds to
      sequences which resemble the target sequences of SRF and MCM1, and have
      determined the consensus sequence to which AGL3 binds using random
      oligonucleotides. These results suggest that AGL3 is a widely distributed DNA
      binding protein, which may be involved the transcriptional regulation of genes in
      many cells.

PMID- 7632924
TI  - Extreme heterogeneity of polyadenylation sites in mRNAs encoding chloroplast RNA
      binding proteins in Nicotiana plumbaginifolia.
AB  - We have previously characterized nuclear cDNA clones encoding two RNA binding
      proteins, CP-RBP30 and CP-RBP-31, which are targeted to chloroplasts in Nicotiana
      plumbaginifolia. In this report we describe the analysis of the 3'-untranslated
      regions (3'-UTRs) in 22 CP-RBP30 and 8 CP-RBP31 clones which reveals that mRNAs
      encoding both proteins have a very complex polyadenylation pattern. Fourteen
      distinct poly(A) sites were identified among CP-RBP30 clones and four sites among
      the CP-RBP31 clones. The authenticity of the sites was confirmed by RNase A/T1
      mapping of N. plumbaginifolia RNA. CP-RBP30 provides an extreme example of the
      heterogeneity known to be a feature of mRNA polyadenylation in higher plants.
      Using PCR we have demonstrated that CP-RBP genes in N. plumbaginifolia and N.
      sylvestris, in addition to the previously described introns interrupting the
      coding region, contain an intron located in the 3' non-coding part of the gene.
      In the case of the CP-RBP31, we have identified one polyadenylation event
      occurring in this intron.

PMID- 7632925
TI  - Up-regulation of a cysteine protease accompanies the ethylene-insensitive
      senescence of daylily (Hemerocallis) flowers.
AB  - The flowers of daylily (Hemerocallis x hybrida cv. Cradle Song) open at midnight,
      start to senesce 12 h later, and are completely senescent by the following
      midnight. Differential screening of a cDNA library constructed from tepals of
      flowers showing incipient senescence revealed 25 clones that were strongly up
      regulated in senescent tepals. Re-screening and interactive Southern analysis of
      these clones revealed 3 families of up-regulated clones. Transcripts of one
      clone, SEN10, were not detectable at midnight, but increased dramatically as
      senescence proceeded. The derived amino acid sequence of the full-length cDNA
      (SEN102) has strong homology with cysteine proteases that have been reported from
      other plant tissues. The sequence contains a secretory signal peptide and a
      probable prosequence upstream of the mature protein. Amino acids critical to the
      active site and structure of cysteine proteases are conserved, and the C-terminus
      of the polypeptide has a unique putative endoplasmic reticulum retention signal 
      RDEL.

PMID- 7632926
TI  - The transcripts encoding two oleosin isoforms are both present in the aleurone
      and in the embryo of barley (Hordeum vulgare L.) seeds.
AB  - Two transcripts (Ole-1 and Ole-2) encoding two oleosin isoforms homologous to the
      18 and 16 kDa oleosins of maize, respectively, have been isolated from developing
      barley embryos and aleurone layers where lipid bodies are highly abundant
      organelles. For each of the isoforms the aleurone and embryo transcripts are
      identical, indicating that the same genes are expressed in both tissues. The
      temporal accumulation of the two transcripts during seed development is similar.
      At a low frequency, lipid bodies are found also in starchy endosperm cells of
      barley. Accordingly, a low transcript level is observed for both oleosins during
      starchy endosperm development.

PMID- 7632927
TI  - Identification of a gibberellin-induced gene in deepwater rice using differential
      display of mRNA.
AB  - Differential display of mRNA was employed to identify gibberellin (GA)-regulated
      genes in deepwater rice. One of the first differentially displayed products
      identified was shown to be ten-fold induced after start of GA treatment. The
      sequence of the clone shows complete amino acid identity with histone H3, and its
      increased mRNA level correlates with the onset of DNA synthesis. We also
      identified a gene whose expression pattern did not change over the course of
      treatment with GA and can be used as standard to correct for loading differences
      on northern blots.

PMID- 7632928
TI  - Interleukin-6 family of cytokines and gp130.

PMID- 7632929
TI  - Peripheral T-cell lymphoma in lckpr-bcl-2 transgenic mice.
AB  - t(14;18) is the most common translocation in human lymphoid malignancy and
      results in bcl-2 overexpression. Bcl-2 blocks apoptosis and constitutes the
      initial member of a new category of oncogenes, ie, regulators of cell death. Bcl
      2-Ig transgenic mice develop follicular hyperplasia and progress to malignant B
      cell lymphoma. To assess the oncogenic potential of bcl-2 in the T-cell lineage,
      a cohort of 68 lckpr-bcl-2 transgenic mice and 56 control littermates were
      monitored for signs of malignancy over a 24-month period. Eighteen (26%) lckpr
      bcl-2 mice developed diffuse, predominantly large-cell lymphomas at a mean age of
      18 months. In contrast, only one nontransgenic control mouse developed lymphoma.
      CD3 surface expression and clonal T-cell receptor beta rearrangements support the
      T-lineage classification of these neoplasms. lckpr-bcl-2-enforced lymphomas are
      predominantly CD4+CD8-, consistent with a mature peripheral T-cell phenotype.
      These data provide support for the thesis that violation of homeostasis through
      the repression of cell death can be a primary mechanism of tumorigenesis in
      multiple lineages.

PMID- 7632930
TI  - Adoptive immunotherapy evaluating escalating doses of donor leukocytes for
      relapse of chronic myeloid leukemia after bone marrow transplantation: separation
      of graft-versus-leukemia responses from graft-versus-host disease.
AB  - Infusions of large numbers (> 10(8)/kg) of donor leukocytes can induce remissions
      in patients with chronic myeloid leukemia (CML) who relapse after marrow
      transplantation. We wanted to determine if substantially lower numbers of donor
      leukocytes could induce remissions and, if so, whether this would reduce the 90%
      incidence of graft-versus-host disease (GVHD) associated with this therapy.
      Twenty-two patients with relapsed CML were studied: 2 in molecular relapse, 6 in
      cytogenetic relapse, 10 in chronic phase, and 4 in accelerated phase. Each
      patient received escalating doses of donor leukocytes at 4- to 33-week intervals.
      Leukocyte doses were calculated as T cells per kilogram of recipient weight.
      There were 8 dose levels between 1 x 10(5) and 5 x 10(8). Lineage-specific
      chimerism and residual leukemia detection were assessed using sensitive
      polymerase chain reaction (PCR) methodologies. Nineteen of the 22 patients
      achieved remission. Remissions were achieved at the following T-cell doses: 1 x
      10(7) (n = 8), 5 x 10(7) (n = 4), 1 x 10(8) (n = 3), and 5 x 10(8) (n = 4). To
      date, 15 of the 17 evaluable patients have become BCR-ABL negative by PCR. The
      incidence of GVHD was correlated with the dose of T cells administered. Only 1 of
      the 8 patients who achieved remission at a T-cell dose of 1 x 10(7)/kg developed
      GVHD, whereas this complication developed in 8 of the 11 responders who received
      a T-cell dose of > or = 5 x 10(7)/kg. Three patients died in remission, 1
      secondary to marrow aplasia, 1 of respiratory failure and 1 of complications of
      chronic GVHD. Sixteen patients who were mixed T-cell chimeras before treatment
      became full donor T-cell chimeras at the time of remission. Donor leukocytes with
      a T-cell content as low as 1 x 10(7)/kg can result in complete donor chimerism
      together with a potent graft-versus-leukemia (GVL) effect. The dose of donor
      leukocytes or T cells used may be important in determining both the GVL response
      and the incidence of GVHD. In many patients, this potent GVL effect can occur in
      the absence of clinical GVHD.

PMID- 7632931
TI  - Homozygous deletions of p16/MTS1 gene are frequent but mutations are infrequent
      in childhood T-cell acute lymphoblastic leukemia.
AB  - Fifty-six primary childhood T-cell acute lymphoblastic leukemia (T-ALL) samples
      and 17 T-ALL cell lines were examined for mutations and homozygous deletions of
      the p16/MTS1 gene using polymerase chain reaction single-strand conformation
      polymorphism and Southern blot analysis. Homozygous deletions were found in 22
      primary samples (39%) and in 10 cell lines (59%). In contrast, mutations
      including small deletions and/or insertions were identified in only 4 primary
      samples (7%) and in 2 cell lines (12%). Mutations included samples (7%) and in 2
      cell lines (12%). Mutations included one nonsense mutation at codon 72, one
      missense mutation at codon 58, one deletion (29 bp from codon 52-61), one
      insertion (7 bp into codon 50), and two deletion/insertions (codon 63 and intron
      1). Four of the six mutations caused subsequent stop codon and presumably
      produced truncated p16 protein. Our results suggest that p16 gene alterations are
      involved in the development of T-ALLs and that the inactivation of the p16 gene
      occurs mainly through homozygous deletions rather than mutations.

PMID- 7632932
TI  - Kaposi's sarcoma-associated herpesvirus-like DNA sequences in multicentric
      Castleman's disease.
AB  - Multicentric Castleman's disease (MCD) is an atypical lymphoproliferative
      disorder defined using clinical and pathologic criteria. A characteristic of the
      MCD is a close association with Kaposi's sarcoma (KS), which occurs during the
      clinical course of most human immunodeficiency virus (HIV)-associated MCD cases
      and also, but less frequently, in HIV-negative patients. Recently, sequences of a
      putative new Herpesvirus (KSHV) have been isolated and further detected in almost
      all the acquired immunodeficiency syndrome (AIDS) KS and in most of the non-AIDS
      KS samples. In this study, we searched for these Herpesvirus-like sequences in
      MCD samples of 31 patients. KSHV sequences were detected in 14 of 14 cases of HIV
      associated MCD, including 5 cases without detectable KS. Moreover, KSHV was
      detected in 7 of 17 MCD cases in HIV-negative patients, including 1 case
      associated with a cutaneous KS. In 34 non-MCD reactive lymph nodes (follicular
      and/or interfollicular hyperplasia) in HIV-negative patients, KSHV was detected
      in only 1 case. In 1 HIV-negative case of MCD, KSHV was found in both the lymph
      node and peripheral blood samples. These data suggest that KSHV could play a role
      in the pathogenesis of MCD, especially in HIV-infected patients.

PMID- 7632933
TI  - Inhibition of productive human immunodeficiency virus-1 infection by cobalamins.
AB  - Various cobalamins act as important enzyme cofactors and modulate cellular
      function. We investigated cobalamins for their abilities to modify productive
      human immunodeficiency virus-1 (HIV-1) infection of hematopoietic cells in vitro.
      We show that hydroxocobalamin (OH-Cbl), methylcobalamin (Me-Cbl), and
      adenosylcobalamin Ado-Cbl (Ado-Cbl) inhibit HIV-1 infection of normal human blood
      monocytes and lymphocytes. The inhibitory effects were noted when analyzing the
      monocytotropic strains HIV-1-BaL and HIV-1-ADA as well as the lymphocytotropic
      strain HIV-1-LAI. Cobalamins did not modify binding of gp120 to CD4 or block
      early steps in viral life cycle, inhibit reverse transcriptase, inhibit induction
      of HIV-1 expression from cells with established or latent infection, or modify
      monocyte interferon-alpha production. Because of the ability to achieve high
      blood and tissue levels of cobalamins in vivo and the general lack of toxicity,
      cobalamins should be considered as potentially useful agents for the treatment of
      HIV-1 infection.

PMID- 7632934
TI  - Interleukin-6-associated anemia: determination of the underlying mechanism.
AB  - Recombinant human interleukin-6 (rhIL-6) is a pluripotent cytokine with
      proinflammatory, antitumor, and growth factor effects. Clinical investigations of
      rhIL-6 either alone as immunotherapy or as a colony-stimulating factor in
      conjunction with chemotherapy have shown a dose-dependent, rapid onset, and
      largely reversible decrease in venous hematocrit levels. In an effort to
      determine the mechanism for the rhIL-6-associated anemia, we measured red blood
      cell volume serially in patients receiving rhIL-6 at either 30 micrograms/kg/day
      as a 120-hour continuous intravenous infusion (renal cell carcinoma) or 100
      micrograms/kg/d intravenously over 1 hour for 5 days (melanoma) as part of two
      separate phase II trials. Radioisotope dilution assays with 51Cr-labeled
      autologous red blood cells and hemolysis screens were performed on day 1 before
      the initiation of therapy and on day 5 shortly before the end of therapy. In the
      6 patients studied, the mean decrease in hemoglobin concentration was 1.9 +/-
      0.94 g/dL. The mean decrease in the hematocrit level was 6% +/- 2% and the mean
      increase in total blood volume was 731 +/- 337 mL. These changes were explained
      by a mean decrease in red blood mass of 106 +/- 109 mL and a mean increase in
      plasma volume of 743 +/- 289 mL. The decrease in red blood cell mass was largely
      explained by phlebotomy during the hospitalization, but was not statistically
      significant (paired t-test, P = .06). All other changes were statistically
      significant (P < .05). Simple regression analysis indicated that the decrease in
      hematocrit level and increase in plasma volume were related (y = -1.78 - .0066X;
      R = -.74). Measurements of lactate dehydrogenase, bilirubin, haptoglobin, and
      reticulocyte counts and serial stool hemoccults did not indicate hemolysis or
      blood loss. We conclude that the anemia caused by IL-6 is caused by an increase
      in plasma volume.

PMID- 7632935
TI  - Persistence of circulating blasts after 1 week of multiagent chemotherapy confers
      a poor prognosis in childhood acute lymphoblastic leukemia.
AB  - Early response to therapy, typically assessed by bone marrow status, is
      predictive of outcome in childhood acute lymphoblastic leukemia (ALL). Less is
      known about the significance of early clearance of blast cells in peripheral
      blood. We reviewed medical records of all patients with ALL enrolled on St Jude
      Total Therapy Study XI (February 1984 to September 1988) to determine the
      presence of blast cells in peripheral blood at diagnosis and after 1 week of
      intensive induction therapy. Of the 358 patients, 59 lacked evidence of
      circulating blast cells at diagnosis, and data were unavailable for 2 patients.
      The prognostic significance of persistent circulating blast cells in the
      remaining 297 patients was assessed in a multivariate analysis that included
      known adverse prognostic factors. Persistent circulating leukemic blasts were
      present at day 8 in 41 patients (14%). Compared with the "blast-negative" group,
      these patients had a significantly higher frequency of several adverse clinical
      features (leukocyte count > 50 x 10(9)/L, mediastinal mass, central nervous
      system leukemia, T-cell phenotype, lack of CD10 expression, and L2 morphology)
      and a significantly poorer 5-year event-free survival (34% +/- 8% [SE] v 77% +/-
      3%, P < .01). By multivariate analysis, blast cell persistence at week 1 was the
      most significant adverse feature in the overall cohort (relative risk, 2.9; 95%
      confidence interval, 1.8 to 4.8) and in an analysis limited to B-lineage cases
      (relative risk, 3.6; 95% confidence interval, 1.9 to 7.1). Patients identified by
      this simple, noninvasive measure may benefit from early modification of therapy.

PMID- 7632936
TI  - Interferon maintenance therapy for patients with chronic lymphocytic leukemia in
      remission after fludarabine therapy.
AB  - Many patients with chronic lymphocytic leukemia (CLL) achieve remission after
      treatment with fludarabine chemotherapy. Most of these patients, however, later
      experience relapse. In addition, immunologic deficits may persist even in
      patients in complete remission; lymphopenia, predominantly involving the CD4
      population, is universal after fludarabine therapy. We used recombinant alpha
      interferon (IFN-alpha) maintenance therapy in patients with CLL who achieved
      remission in response to fludarabine therapy to determine its effect on residual
      disease, assessed by either bone marrow biopsy or flow cytometry, and on immune
      restoration. Thirty-one patients were treated with IFN-alpha (3 x 10(6) U by
      subcutaneous injection three times weekly). Twenty-two patients (71%) were in
      complete remission (CR) and nine (29%) were in partial remission (PR). Of the 22
      patients in CR, 21 (95%) had evidence of residual disease at the start of IFN
      alpha therapy. Low CD4 levels were noted in 93% of patients, low IgG levels in
      45%, and anergy or hypoergy in 52%. Only one patient in PR achieved a CR on IFN
      alpha therapy: the only patient who had had no prior fludarabine but had been
      treated with chlorambucil and prednisone. All patients in CR with minimal
      residual disease had persistent disease after IFN-alpha treatment. There were no
      increases in CD4 counts or IgG levels; three patients with borderline responses
      to skin testing had an increase in the number of positive tests while on IFN
      alpha. The time to progression was no different in patients treated with IFN
      alpha than in a historical control group of patients who had received no further
      therapy after fludarabine. In summary, the use of IFN-alpha maintenance did not
      eradicate residual disease, restore immune function, or prolong remissions in
      patients with CLL responsive to fludarabine.

PMID- 7632937
TI  - Thrombocytopoietic properties of oncostatin M.
AB  - Oncostatin M (OM) is a 28-kD glycoprotein that exhibits a panoply of biologic
      effects. Based on histologic observations of increased splenic megakaryocytes in
      nude mice implanted with an OM-secreting cell line, the thrombocytopoietic
      properties of OM in mice were investigated in culture and in vivo. Alone, OM did
      not induce megakaryocytic colony formation, but in combination with murine
      interleukin-3 (IL-3), OM markedly enhanced colony formation. The effects of OM on
      colony formation were similar to those of IL-6. OM alone augmented
      acetylcholinesterase in short-term marrow cultures. In normal mice, the
      administration of OM augmented platelet counts without increasing other
      circulating blood cell counts. The increment in counts exceeded that observed
      with IL-6. The kinetics of the OM response suggested that maximal increases in
      platelets occurred 3 days after the cessation of OM administration, irrespective
      of the duration of administration. In irradiated mice, OM administration
      accelerated platelet recovery and prevented the decrease in red blood cells
      observed in irradiated control animals. The data show that OM behaves as a
      megakaryocytic maturation factor in vitro and augments platelet production in
      vivo. Based on these animal data, OM may have potential clinical utility as a
      thrombocytopoietic agent.

PMID- 7632938
TI  - Murine embryonic yolk sac cells promote in vitro proliferation of bone marrow
      high proliferative potential colony-forming cells.
AB  - To examine the influence of the hematopoietic microenvironment on hematopoietic
      cell proliferation and differentiation during the yolk sac phase of
      hematopoiesis, we have recently established cell lines from embryonic yolk sac
      visceral endoderm (YSE) and mesoderm (YSM). In the present experiments, we
      compared in vitro growth of adult murine bone marrow high proliferative potential
      colony-forming cells (HPP-CFC) in coculture with YSE- and YSM-derived or adult
      bone marrow stromal cell lines. Whereas both yolk sac-derived and adult stromal
      cell lines supported the proliferation of HPP-CFC during coculture, YSE- and YSM
      derived cells stimulated a significant increase in total HPP-CFC compared with
      adult bone marrow stromal cell lines. Conditioned media from both YSE- and YSM
      derived cell lines also stimulated the growth of HPP-CFC in vitro, but only in
      combination with exogenous recombinant hematopoietic growth factors. Although
      multiple hematopoietic growth factor mRNAs were detected in the yolk sac-derived
      cells by polymerase chain reaction, only macrophage colony-stimulating factor (M
      CSF) activity was detected in conditioned media using an enzyme-linked
      immunosorbent assay. A neutralizing polyclonal antibody against M-CSF did not
      diminish the YSE- or YSM-derived cell line conditioned media promotion of HPP-CFC
      colony formation. These results suggest that murine yolk sac-derived cell lines
      produce a novel soluble factor(s) that recruits primitive bone marrow
      hematopoietic cells to grow in vitro in response to a combination of
      hematopoietic growth factors.

PMID- 7632939
TI  - Modulation of megakaryocytopoiesis by thrombopoietin: the c-Mpl ligand.
AB  - We have further characterized the biological activities, mechanism of action, and
      target cell populations of recombinant human and murine thrombopoietin (rhTPO and
      rmTPO) in in vitro human and murine model systems. Alone, hTPO or mTPO stimulated
      the maturation of immature murine megakaryoblasts as measured in a single cell
      assay. The combination of hTPO or mTPO and interleukin-6 (IL-6) resulted in a
      further increase in megakaryocyte differentiation in this system. Murine TPO
      stimulated mouse megakaryocyte progenitor development. Human megakaryocyte
      progenitor development was potentiated by hTPO alone and further augmented in the
      presence of the early-acting cytokines (IL-3) or kit ligand/stem cell factor
      (KL/SCF). To further define the mechanism of action of TPO, neutralization
      studies were performed with antisera to IL-3, granulocyte-macrophage colony
      stimulating factor (GM-CSF), IL-1 beta, and IL-11. No diminution in TPO activity
      was observed in the presence of these antisera. Moreover, because adhesive
      interactions are known to modulate hematopoiesis, we studied whether hTPO might
      alter such interactions between human bone marrow (BM) megakaryocytes and human
      BM stromal fibroblasts. No changes were observed in either megakaryocyte
      expression of the surface molecules lymphocyte function-associated antigen-1,
      very late activation antigen-4, or intercellular adhesion molecule-1 or the
      adhesion of megakaryocytes to stromal fibroblasts after treatment with the growth
      factor. Furthermore, no induction of secretion of the cytokines IL-1 alpha, IL-1
      beta, GM-CSF, IL-6, granulocyte-CSF, tumor necrosis factor-alpha, transforming
      growth factor-beta 1, or transforming growth factor-beta 2 by primary human BM
      megakaryocytes was noted after treatment of the cells with hTPO. To address
      whether TPO affects very primitive hematopoietic progenitors, we studied the
      residual cells from the BMs of mice treated with high doses of 5-fluorouracil.
      Although no effect of mTPO alone was noted on the viability or replication of
      such primitive murine progenitor populations, the triple combination of IL-3 +
      KL/SCF + TPO stimulated growth of megakaryocyte progenitors. These results
      indicate that TPO is a highly lineage-specific growth factor whose primary
      biological effects are likely to be direct modulation of the growth and
      maturation of committed megakaryocyte precursors and immature megakaryoblasts.

PMID- 7632940
TI  - Characterization and purification of a primitive hematopoietic cell type in adult
      mouse marrow capable of lymphomyeloid differentiation in long-term marrow
      "switch" cultures.
AB  - In this report, we describe a modification of the assay for long-term culture
      initiating cells (LTC-IC) that allows a subset of murine LTC-IC (designated as
      LTC-ICML) to express both their myeloid (M) and lymphoid (L) differentiative
      potentials in vitro. The modified assay involves culturing test cells at limiting
      dilutions on irradiated mouse marrow feeder layers for an initial 4 weeks under
      conditions that support myelopoiesis and then for an additional week under
      conditions permissive for B-lymphopoiesis. All of the clonogenic pre-B
      progenitors (colony-forming unit [CFU] pre-B) detected in such postswitch LTC
      appear to be the progeny of uncommitted cells present in the original cell
      suspension because exposure of lymphoid-restricted progenitors to myeloid LTC
      conditions for > or = 7 days was found to irreversibly terminate CFU-pre-B
      production and, in cultures initiated with limiting numbers of input cells (no
      progenitors of any type detected in > 70% of cultures 1 week after the switch),
      the presence of CFU-pre-B was tightly associated with the presence of myeloid
      clonogenic cells, regardless of the purity of the input population. Limiting
      dilution analysis of the proportion of negative cultures measured for different
      numbers of input cells showed the frequency of LTC-ICML in normal adult mouse
      marrow to be 1 per 5 x 10(5) cells with an enrichment of approximately 500-fold
      in the Sca-1+ Lin-WGA+ fraction, as was also found for competitive in vivo
      repopulating units (CRU) and conventionally defined LTC-IC. LTC-ICML also
      exhibited the same resistance to treatment in vivo with 5-fluorouracil (5-FU) as
      CRU and LTC-IC, thereby distinguishing these three populations from the great
      majority of both in vitro clonogenic cells and day 12 CFU-S. The ability to
      quantitate cells with dual lymphoid and myeloid differentiation potentials in
      vitro, without the need for their prior purification, should facilitate studies
      of totipotent hematopoietic stem cell regulation.

PMID- 7632941
TI  - Molecular cloning of cDNA encoding a novel platelet-endothelial cell tetra-span
      antigen, PETA-3.
AB  - Platelet-endothelial cell tetra-span antigen (PETA-3) was originally identified
      as a novel human platelet surface glycoprotein, gp27, which was detected by a
      monoclonal antibody (MoAb), 14A2.H1. Although this glycoprotein is present in low
      abundance on the platelet surface, MoAb 14A2.H1 stimulates platelet aggregation
      and mediator release. We now report isolation of a cDNA clone encoding PETA-3
      from a library derived from the megakaryoblastic leukemia cell line MO7e. The
      clone encodes an open reading frame of 253 amino acids that displays 25% to 30%
      amino acid sequence identity with several members of the newly defined Tetraspan,
      or Transmembrane 4 superfamily. These proteins consist of four conserved putative
      transmembrane domains with a large divergent extracellular loop between the third
      and fourth membrane-spanning regions. PETA-3 has a single consensus sequence for
      N-linked glycosylation located in this extracellular loop. A single PETA-3 RNA
      transcript (1.6 kb) was detected in RNA isolated from MO7e cells, bone marrow
      stromal cells, the C11 endothelial cell line, and several myeloid leukemia cell
      lines. No transcript was detected in the lymphoblastoid cell lines MOLT-4 and
      BALM-1. This pattern correlates well with previous protein expression data.
      Northern blot analysis of RNA from a range of human tissues indicated that the
      transcript was present in most tissues, the notable exception being brain.

PMID- 7632942
TI  - The largest variant of platelet glycoprotein Ib alpha has four tandem repeats of
      13 amino acids in the macroglycopeptide region and a genetic linkage with
      methionine145.
AB  - Platelet membrane glycoprotein Ib alpha (GPIb alpha) bears the human platelet
      alloantigen (HPA)-2 and molecular weight (MW) polymorphisms on sodium dodecyl
      sulfate-polyacrylamide gels. HPA-2 arises from a threonine/methionine dimorphism
      at residue 145 of the GPIb alpha sequence, whereas different numbers of tandem
      repeats of a 39-bp sequence encoding 13-amino acids corresponding to a region
      between serine399 and threonine411 of the GPIb alpha account for the latter. To
      identify the genetic basis of the MW polymorphism among Japanese, we counted the
      tandem repeats in 103 individuals. In addition to the reported three variants
      with one, two, or three tandem repeats, we identified a new variant with four
      perfect tandem repeats of the 39-bp sequence that corresponded to the largest
      phenotype. Phenotypic analysis of the MW polymorphism on 12 individuals including
      all four phenotypes completely accorded in the genotype. We also determined the
      genotype of HPA-2 and found that methionine145 was in complete linkage
      disequilibrium, with the larger variants containing three or four tandem repeats.
      These results imply a model of evolutionary steps in the gene encoding GPIb
      alpha.

PMID- 7632943
TI  - Human platelet glycoprotein V: its role in enhancing expression of the
      glycoprotein Ib receptor.
AB  - Platelet adhesion to an injured blood vessel wall is a critical initiating step
      in hemostasis mediated by a four member receptor complex (glycoprotein Ib/V/IX)
      interacting with plasma von Willebrand factor (vWF). The function of the GPV
      subunit within this complex is presently undefined. To study the role of
      glycoprotein (GP) V within the GPIb receptor complex, we transfected the GPV
      subunit gene into a hematopoietic cell line that constitutively expresses the
      other three subunits (human erythroleukemia [HEL] cells). Using flow cytometry,
      we found transfected GPV was surface expressed in HEL cells; this, in turn, led
      to increased surface expression of the ligand-binding GPIb alpha and GPIX
      subunits. Radioligand binding assays showed that GPV-transfected HEL cells bound
      more vWF than their non- or mock-transfected counterparts. We employed confocal
      microscopy of GPV-transfected HEL cells to show that GPV colocalizes with GPIb
      alpha on the cell surface. These findings suggest that the GPV subunit plays a
      role within the GPIb receptor complex by enhancing Ib alpha surface expression.

PMID- 7632944
TI  - The effects of low molecular weight and standard heparin on calcium loss from
      fetal rat calvaria.
AB  - Osteoporosis is a well-recognized complication of long-term heparin use. However,
      the mechanisms by which heparin can influence bone metabolism are unclear. We
      report here that unfractionated heparin stimulates the process of bone resorption
      and that the low molecular weight heparins (LMWHs), enoxaparin, fragmin,
      logiparin, and ardeparin produce significantly less calcium loss than
      unfractionated heparin. To assess calcium loss from bone, we quantified the
      release of 45Ca into the culture medium of fetal rat calvaria. 45Ca release was
      increased in a dose-dependent manner by the addition of either unfractionated
      heparin or the LMWHs; but more than 50-fold higher LMWH concentrations were
      required to obtain an equivalent effect to unfractionated heparin. Thus, at
      concentration > or = 2 micrograms/mL (0.35 anti-Xa units/mL), unfractionated
      heparin stimulated 45Ca release 1.53 +/- 0.06 fold. 45Ca release was increased to
      a similar extent by the addition of either 10(-7) mol/L parathyroid hormone (PTH)
      or 10(-6) mol/L 1,25 dihydroxyvitamin D3 (1,25 Vit D3). In contrast to
      unfractionated heparin, LMWH concentrations > or = 100 micrograms/mL (> or = 14.0
      anti-Xa units/mL) were required before maximum isotope release was observed. At
      concentrations well above therapeutic levels, the LMWHs stimulated 45Ca release
      by only 1.25 /+- 0.01-fold. Heparins with high and low antithrombin III
      affinities stimulated 45Ca release equally well. Both size and sulfation were
      found to be major determinants of heparin's ability to promote isotope release.
      Thus, the ability of defined heparin fragments to stimulate 45Ca release
      correlated with their molecular weight, and after N-desulfation the ability of
      heparin to induce isotope release was greatly diminished. Dermatan sulfate had no
      effect on 45Ca release. We conclude that size and sulfation are major
      determinants of heparin's ability to promote bone resorption and that the risk of
      heparin-induced osteoporosis may be reduced by the use of LMWH preparations.

PMID- 7632945
TI  - CD3- large granular lymphocytes recognize a heat-inducible immunogenic
      determinant associated with the 72-kD heat shock protein on human sarcoma cells.
AB  - Traditionally, heat shock proteins (HSPs) are believed to be located
      intracellularly, where they perform a variety of chaperoning functions. Recently,
      evidence has accumulated that some tumor cells express HSPs on the cell surface.
      The present study confirms this finding and correlates HSP72 cell surface
      expression, induced by nonlethal heat shock, with an increased sensitivity to
      interleukin-2-stimulated CD3-natural killer (NK) cells. After nonlethal heat
      shock, a monoclonal antibody directed against the major heat-inducible 72-kD HSP
      (HSP72) stains the cell surface of sarcoma cells (ie, Ewing's sarcoma cells or
      osteosarcoma cells) but not that of normal cells (ie, peripheral blood
      lymphocytes, fibroblasts, phytohemagglutin-stimulated blasts, B-lymphoblastoid
      cell lines) or of mammary carcinoma cell line MX-1 carcinoma cells. In this
      study, we show for the first time a correlation of HSP72 cell surface expression
      with an increased susceptibility to lysis by NK effector cells. This finding is
      supported by the following points: (1) HLA-disparate effector cells show similar,
      elevated lysis of HSP72+ heat-treated sarcoma cells; (2) CD(3-) NK cells, but not
      CD3+ cytotoxic T lymphocytes, are responsible for the recognition of heat-shocked
      sarcoma cells; (3) by antibody-blocking studies, an immunogenic HSP72
      determinant, which is expressed selectively on the cell surface of heat-treated
      sarcoma cells could be correlated with NK recognition; (4) the reported
      phenomenon is independent of a heat-induced, transient downregulation of major
      histocompatibility complex (MHC) class-I expression; and (5) blocking of MHC
      class-I-restricted recognition, using either MHC class-I-specific monoclonal
      antibody W6/32 on the target cells or alpha/beta T-cell receptor monoclonal
      antibody WT31 on effector cells, also has no inhibitory effect on the lysis of
      HSP72+ tumor cells. Finally, our in vitro data might have further clinical
      implications with respect to HSP72 as a stress-inducible, sarcoma-specific NK
      recognition structure.

PMID- 7632946
TI  - Decreased levels of total and reduced glutathione in CD4+ lymphocytes in common
      variable immunodeficiency are associated with activation of the tumor necrosis
      factor system: possible immunopathogenic role of oxidative stress.
AB  - We have previously shown chronic immune activation and enhanced generation of
      reactive oxygen species in common variable immunodeficiency (CVI). In the present
      study, we examined levels of glutathione, the dominant intracellular thiol, that
      play an important protective role against oxidative and inflammatory stress in
      plasma and in monocytes and lymphocyte subsets in 20 CVI patients and in 16
      healthy controls. CD4+ lymphocytes from CVI patients had significantly lower
      levels of both total and reduced glutathione as well as a lower ratio of reduced
      to total glutathione compared with healthy controls. This decrease in glutathione
      levels in CD4+ lymphocytes was most pronounced in the CD45RA+ subset. Plasma
      levels of total glutathione were also significantly decreased in CVI. In
      contrast, monocytes from CVI patients exhibited increased levels of both total
      and reduced glutathione compared with blood donor monocytes. CVI patients had
      significantly raised serum levels of tumor necrosis factor alpha (TNF alpha) and
      TNF alpha concentration was strongly associated with glutathione depletion in
      CD4+ lymphocytes. Furthermore, the lowest levels of both total and reduced
      glutathione were found in a subgroup of CVI patients characterized by persistent
      immune activation in vivo, decreased numbers of CD4+ lymphocytes in peripheral
      blood, and splenomegaly. Finally, supplementation of cell cultures with
      glutathione-monoethyl ester did significantly enhance interleukin-2 production
      from peripheral blood mononuclear cells in CVI patients. These glutathione
      abnormalities in CVI indicate increased oxidative stress, particularly in CD4+
      lymphocytes, and intracellular depletion of reduced glutathione of the
      demonstrated magnitude may have profound implications for CD4+ lymphocyte
      function and the immunodeficiency in CVI.

PMID- 7632947
TI  - Delineation of an immunodominant and human T-cell lymphotropic virus (HTLV)
      specific epitope within the HTLV-I transmembrane glycoprotein.
AB  - Antibody reactivity to the transmembrane region of human T-cell lymphotropic
      virus type I (HTLV-I) envelope, gp21, is observed in virtually all individuals
      infected with HTLV-I or HTLV-II. Recombinant proteins encoding selected portions
      of gp21 are described and used to define two immunogenic regions. The first
      epitope (designated GD21-I) contains amino acids 361 to 404 of the HTLV-I
      envelope and reacted with all of 54 sera from HTLV-I- and HTLV-II-infected
      individuals. The second epitope (designated BA21) expresses amino acids 397 to
      430 of the HTLV-I envelope and was recognized by 33 of 54 HTLV antisera. To
      determine the specificity of GD21-I and BA21, sera from 17 HTLV-negative
      individuals with nonspecific reactivity to p21E were tested. None of these sera
      reacted with GD21-I, but 16 of 17 sera reacted with BA21. With virtually complete
      reactivity to sera from HTLV-infected individuals and no reactivity to sera from
      p21E-reactive uninfected individuals, GD21-I will be useful in immunoassays for
      the detection of HTLV infection.

PMID- 7632948
TI  - T-cell death by apoptosis in vertically human immunodeficiency virus-infected
      children coincides with expansion of CD8+/interleukin-2 receptor-/HLA-DR+ T
      cells: sign of a possible role for herpes viruses as cofactors?
AB  - One mechanism proposed to play a role in T-cell depletion in human
      immunodeficiency virus (HIV) infection is apoptosis (activation-induced cell
      death). We assessed whether apoptosis is related to activation of T cells in vivo
      and its possible triggers. DNA was extracted from peripheral blood mononuclear
      cells (PBMC) taken from 16 vertically HIV-infected children and 9 HIV-negative
      children born to HIV-positive mothers (controls) and tested by agarose gel
      electrophoresis for the presence of DNA fragments specific for apoptosis. Signs
      of apoptosis were found on in vitro culture of PBMC from 12 of 16 HIV-infected
      children, but not in PBMC from the nine controls. Eleven of the 12 HIV-infected
      children with apoptosis showed an elevated (> 15%) proportion of CD3+/HLA-DR+
      cells. This was due to an increased proportion of CD8+/HLA-DR+ cells, as shown in
      7 of 7 further tested patients. In none of the probands an increased (> 5%)
      proportion of IL-2 receptor expressing CD3+ cells was found. T cells undergoing
      apoptosis were preferentially of the CD8+ phenotype. Expansion of circulating
      CD8+/interleukin-2 receptor (IL-2R)-/HLA-DR+ T cells is known to occur during
      active infection with herpes viruses. To investigate the possible role of herpes
      viral coinfections for apoptosis in HIV infection, we focused on Epstein-Barr
      virus (EBV) as an example for a herpes virus usually acquired during childhood.
      In 10 of 12 patients with apoptosis, we found increased levels of EBV genome in
      PBMC and/or tissues, indicating active EBV replication. By contrast, no increased
      burden of EBV was found in the four HIV-infected patients without apoptosis or in
      the controls. Our data indicate that in children the occurrence of apoptosis in
      HIV infection is closely related to activation of CD8+ T cells. Furthermore,
      primoinfection with or reactivation of herpes viruses, such as EBV, may
      substantially contribute to such T-cell activation and the ensuing apoptosis.
      Additional studies are warranted to evaluate the contribution of herpes virus
      triggered apoptosis to the T-cell loss leading to the acquired immunodeficiency
      syndrome.

PMID- 7632949
TI  - Direct demonstration of cytokine synthesis heterogeneity among human
      memory/effector T cells by flow cytometry.
AB  - The array of cytokines produced by T cells in effector sites is a primary means
      by which these cells mediate host defense. It is well recognized that cloned T
      cells are heterogeneous with regard to cytokine synthesis and, thus, in their
      ability to mediate specific immune responses, but the extent to which the
      patterns of cytokine secretion observed in cloned cells reflect actual
      populations of memory/effector T cells existing in vivo is largely unknown. Here,
      we report our findings using a multiparameter flow cytometric assay that allows
      simultaneous determination of an individual T-cell's ability to produce multiple
      cytokines and its phenotype after only short (4 to 8 hours) in vitro incubation
      with an activating stimulus and the secretion inhibitor Brefeldin A. This assay
      shows a rapid accumulation of interleukin-2 (IL-2), IL-4, and gamma-interferon
      (gamma-IFN) in the cytoplasm of CD4+ cells after stimulation with either
      accessory cell-independent (phorbol 12-myristate 13-acetate [PMA] + ionomycin
      [I]) or accessory cell-dependent (staphylococcal enterotoxins [SE] A and B) T
      cell-activating stimuli. Further analysis showed that production of gamma-IFN and
      IL-4 is predominantly, if not exclusively, restricted to the CD45ROhigh
      memory/effector T-cell subset, whereas IL-2 may be produced by both the
      CD45ROhigh and CD45ROlow subsets. Simultaneous determination of IL-2 and gamma
      IFN production among CD45ROhigh/CD4+ T cells showed distinct subsets that produce
      each of these cytokines alone (an average of 30% for IL-2 alone, 8% for gamma-IFN
      alone), both (16%), or neither (46%). Similar analyses with the small IL-4
      producing memory/effector T-cell subset (only 4.3% of total CD4+/CD45ROhigh T
      cells) showed that an average of 51% of these IL-4-producing cells also
      synthesize average of 51% of these IL-4-producing cells also synthesize IL-2, 23%
      synthesize only IL-4, 16% synthesize all three cytokines, and 9.6% synthesize IL
      4 and gamma-IFN. These patterns of cytokine synthesis were found to be similar
      with both PMA + I and SEA/SEB stimulation and were observed in both peripheral
      blood memory/effector CD4+ T cells and in T cells of similar phenotype obtained
      from cutaneous delayed-type hypersensitivity sites. Taken together, these data
      strongly support the in vivo existence of human memory/effector T-cell subsets
      with "preprogrammed" cytokine synthesis potential, although they suggest that
      these subsets may be more complex than originally proposed in the TH1/TH2
      hypothesis.

PMID- 7632950
TI  - Characterization of B-cell lines established from two X-linked severe combined
      immunodeficiency patients: interleukin-15 binds to the B cells but is not
      internalized efficiently.
AB  - X-linked severe combined immunodeficiency (XSCID) is characterized by absent or
      profoundly reduced numbers of T cells and normal numbers of B cells in the
      circulation. Affected patients have mutations of the interleukin-2 (IL-2)
      receptor gamma chain gene. Using Epstein-Barr virus-transformed B-lymphoblastoid
      cell lines (B-LCLs) established from two unrelated XSCID patients, we could show
      that neither expressed the IL-2 receptor gamma chain on the cell surface. A novel
      cytokine IL-15, which has biologic activities similar to those of IL-2, could
      bind to the XSCID B-LCLs in the absence of the gamma chain, although both the
      beta and gamma chains of the human IL-2 receptor were previously shown to be
      required for IL-15 binding by transfected COS cells. Furthermore, a significant
      reduction and delay of IL-15 internalization by B lymphoblasts from XSCID
      patients was observed when compared with that of normal control B-LCLs. These
      results show the existence of a novel IL-15-specific receptor component that
      contributes to IL-15 binding but is insufficient for IL-15 internalization in the
      absence of the IL-2 receptor gamma chain.

PMID- 7632951
TI  - Human immature thymocytes as target cells of the leukemogenic activity of human T
      cell leukemia virus type I.
AB  - The risk of developing adult T-cell leukemia (ATL) associated with neonatal
      infection by human T-cell leukemia virus type I (HTLV-I) suggests that early
      events triggered by HTLV-I might be of crucial importance in initiating the
      multistep lymphoproliferative process leading several decades later to the
      development of leukemic disease. Thus, infection of thymocytes early in life
      might be directly correlated with the development of ATL. In the present study,
      we show that in vitro infection of mature (CD2+CD3+) or immature (CD2+CD3-)
      thymocytes resulted in the exogenous interleukin (IL)-2-dependent proliferation
      of HTLV-I-positive thymocytes, most of them displaying a CD2+CD3-CD4+ phenotype
      and expressing the CD25 molecule, the alpha chain of the IL-2 receptor.
      Furthermore, the CD80 and CD54 antigens, normally expressed by thymic stromal
      cells, were detected on these transformed thymocytes, indicating that HTLV-I
      infection may disturb the cooperation between thymocytes and their thymic
      environment. These HTLV-I-positive thymocytes were producing significant amounts
      of IL-6, which was found to be implicated in their proliferation and in the
      expression of CD25, as demonstrated by blocking experiments using a monoclonal
      antibody to IL-6. The present study suggests that immature thymocytes may provide
      an environment favorable to the unfolding of events leading to leukemia.

PMID- 7632953
TI  - International Prognostic Index for aggressive non-Hodgkin's lymphoma is valid for
      all malignancy grades.
AB  - An International Prognostic Index (IPI) for patients with aggressive non
      Hodgkin's lymphoma (NHL) has recently been published. The IPI is based on
      pretreatment clinical characteristics and developed on clinical trial patients,
      classified as intermediate grade according to the Working Formulation (WF). We
      applied this IPI in a population-based registry of NHL patients. This registry
      does not have the restrictions that usually hold for patients in clinical trials,
      eg, with respect to age and performance status. Moreover, it covers all the three
      WF classes (low, intermediate, and high). The IPI turned out to be of prognostic
      value for response rate and survival in our unselected cohort of 744 patients, as
      well. In each of the three WF classes separately, the four IPI classes showed
      going from low to high substantially decreasing response rates and survival
      percentages. For our cohort of WF intermediate grade patients 5-year survival
      levels were lower in all four IPI classes (59%, 34%, 14%, and 10%, respectively),
      probably reflecting the selection of clinical trial patients in the original
      study (73%, 51%, 43%, and 26%).

PMID- 7632952
TI  - CD79a: a novel marker for B-cell neoplasms in routinely processed tissue samples.
AB  - The CD79 molecule, comprising two polypeptide chains, mb-1 (CD79a) and B29
      (CD79b), is physically associated in the B-cell membrane with immunoglobulin. It
      transmits a signal after antigen binding and may, therefore, be considered the B
      cell equivalent of CD3. It appears before the pre-B-cell stage, and the mb-1
      (CD79a) chain can still be present at the plasma cell stage. In this report, we
      describe a new anti-CD79a monoclonal antibody, JCB117, which reacts with human B
      cells in paraffin embedded tissue sections, including decalcified bone marrow
      trephines. When tested on a total of 454 paraffin embedded tissue biopsies,
      gathered from a number of different institutions, it reacted with the great
      majority (97%) of B-cell neoplasms, covering the full range of B-cell maturation,
      including 10 of 20 cases of myeloma/plasmacytoma. It is of interest that the
      antibody labels precursor B-cell acute lymphoblastic leukemia samples, making it
      the most reliable B-cell marker detectable in paraffin-embedded specimens in this
      disorder. All neoplasms of T cell or nonlymphoid origin were negative, indicating
      that antibody JCB117 may be of value to diagnostic histopathologists for the
      identification of B-cell neoplasms of all maturation stages.

PMID- 7632954
TI  - Numerical chromosome aberrations are present within the CD30+ Hodgkin and Reed
      Sternberg cells in 100% of analyzed cases of Hodgkin's disease.
AB  - In Hodgkin's disease, cytogenetically aberrant clones have been demonstrated in a
      minority of cases studied. In the remaining cases, only normal metaphases have
      been found, but it is questionable whether normal karyotypes actually correspond
      to the pathognomonic Hodgkin and Reed-Sternberg (HRS) cells. Numerical
      aberrations could be studied by fluorescence in situ hybridization (FISH).
      However, in Hodgkin's disease, the percentage of tumor cells is mostly below the
      detection limit of FISH, which is near 1%. With the technique of simultaneous
      fluorescence immunophenotyping and interphase cytogenetic analysis (FICTION),
      this problem can be overcome. By FICTION, hybridization signals can selectively
      be evaluated within the CD30a+ cell population. We have studied 30
      cytogenetically analyzed cases of Hodgkin's disease by means of FICTION. In all
      cases, we found numerical chromosome aberrations within the majority of CD30+ HRS
      cells. In cases with complex and hyperdiploid karyotypes, the cytogenetic results
      agreed with the FICTION data. There was considerable variability in the
      chromosome numbers, demonstrating that karyotype instability is an in vivo
      phenomenon of HRS cells. Lymphocytes never displayed numerical chromosome
      changes. Our results indicate that HRS cells regularly exhibit numerical
      chromosome aberrations and that the chromosome numbers are always in the
      hyperploid range.

PMID- 7632955
TI  - Translocations and amplification of the BCL2 gene are detected in interphase
      nuclei of non-Hodgkin's lymphoma by in situ hybridization with yeast artificial
      chromosome clones.
AB  - Translocation of the BCL2 gene in B-cell malignancies carrying t(14;18) and
      amplification of the BCL2 gene in a cell line (HBL-2) derived from a non
      Hodgkin's lymphoma (NHL) were detected specifically in both metaphase spreads and
      interphase nuclei by fluorescence in situ hybridization (FISH) using yeast
      artificial chromosomes (YACs). A YAC clone containing the BCL2 gene yA153A6, a
      360-kb clone spanning from approximately 60 kb upstream of BCL2 exon 1 to
      approximately 60 kb 3' of the minor breakpoint cluster region, was used for
      single-color FISH analysis. Seven patients with NHL and one patient with acute
      lymphoblastic leukemia were analyzed for BCL2 translocations. Interphase nuclei
      of NHL patients showed three signals when hybridized with the yA153A6 probe. This
      was expected because the YAC clone spans the BCL2 breakpoint regions on 18q21.3.
      In a patient with acute lymphoblastic leukemia, a positive signal for BCL2 was
      detected on der(14) at band 14q32.33 by single-color FISH with the yA153A6 probe,
      whereas no signals were detected on der(18). The amplification of BCL2 in the HBL
      2 cell line was observed on a characteristic abnormal chromosome 18,
      add(18)(q23); the periodic pattern of the fluorescent signal of this region was
      suggestive of an amplicon. Using double-color FISH with YAC clones containing the
      more centromeric 18q21.3 gene gastrin-releasing peptide (y302F10) and the
      14q32.33 gene (IgH; Y6), we detected t(14;18) by showing the juxtaposition of the
      18q21.3 and 14q32.33 bands on the derivative chromosome 18. Interphase FISH with
      these YAC clones provided a rapid procedure for the diagnosis of B-cell
      malignancies carrying t(14;18). In addition, we showed that translocations and
      amplification of the BCL2 gene can be detected at the single-cell level.

PMID- 7632956
TI  - Emergence of CD52-, phosphatidylinositolglycan-anchor-deficient T lymphocytes
      after in vivo application of Campath-1H for refractory B-cell non-Hodgkin
      lymphoma.
AB  - CD52 is a phosphatidylinositolglycan (PIG)-anchored glycoprotein (PIG-AP)
      expressed on normal T and B lymphocytes, monocytes, and the majority of B-cell
      non-Hodgkin lymphomas. We observed the emergence of CD52- T cells in 3 patients
      after intravenous treatment with the humanized anti-CD52 monoclonal antibody
      Campath-1H for refractory B-cell lymphoma and could identify the underlaying
      mechanism. In addition to the absence of CD52, the PIG-AP CD48 and CD59 were not
      detectable on the CD52- T cells in 2 patients. PIG-AP-deficient T-cell clones
      from both patients were established. Analysis of the mRNA of the PIG-A gene
      showed an abnormal size in the T-cell clones from 1 of these patients, suggesting
      that a mutation in the PIG-A gene was the cause of the expression defect of PIG
      AP. An escape from an immune attack directed against PIG-AP+ hematopoiesis has
      been hypothesized as the cause of the occurrence of PIG-AP-deficient cells in
      paroxysmal nocturnal hemoglobinuria (PNH) and aplastic anemia. Our results
      support the hypothesis that an attack against the PIG-AP CD52 might lead to the
      expansion of a PIG-anchor-deficient cell population with the phenotypic and
      molecular characteristics of PNH cells.

PMID- 7632957
TI  - Local suppression of Epstein-Barr virus (EBV)-specific cytotoxicity in biopsies
      of EBV-positive Hodgkin's disease.
AB  - Epstein-Barr virus (EBV)-positive Hodgkin's and Reed-Sternberg (HRS) cells
      express the virus-encoded latent membrane proteins LMP1 and LMP2 that could serve
      as rejection targets in Hodgkin's disease (HD). To examine whether EBV-triggered
      reactivities can be detected in the tumor, we have compared cytokine mRNA
      expression, cell phenotype, and cytotoxic activity in biopsies from 8 EBV
      carrying and 6 EBV-HD patients. Neither the pattern of lymphokine production nor
      the cell phenotype of the in vivo-activated interleukin-2-responding populations
      provided a clear discrimination between EBV+ and EBV- cases. HLA class I
      restricted EBV-specific cytotoxicity was shown in interleukin-2-dependent
      cultures from 3 of 3 EBV- tumors, whereas cultures from 6 of 6 EBV+ tumors were
      either noncytotoxic or exerted LAK-type cytotoxicity. EBV-specific cytotoxic T
      lymphocyte precursors were present in the blood of 1 patient carrying an EBV+
      tumor. The results suggest that a tumor-associated suppression of EBV-specific T
      cell responses may play an important role in the pathogenesis of EBV+ HD.

PMID- 7632958
TI  - Lineage-restricted regulation of the murine SCL/TAL-1 promoter.
AB  - The SCL/TAL-1 gene encodes a basic helix-loop-helix transcription factor that is
      expressed in multipotent hematopoietic progenitors before lineage commitment. Its
      expression is maintained during differentiation along erythroid, mast, and
      megakaryocytic lineages, but is repressed after commitment to nonexpressing
      lineages. To begin to address the molecular mechanisms underlying this complex
      pattern of expression, we have studied the regulation of the murine SCL promoter
      in erythroid and T-cell lines. Analysis of the methylation and chromatin
      structure of the SCL promoter region showed that SCL mRNA expression correlated
      with DNase hypersensitive sites and methylation status of the promoter. Transient
      reporter assays showed that promoter 1a was active in erythroid cells but not in
      T cells. Sequences between -187 and +26 were sufficient for lineage-restricted
      activity of promoter 1a. A joint promoter construct containing both promoter 1a
      and promoter 1b also exhibited lineage-restricted activity. Conserved GATA (-37),
      MAZ (+242), and ETS (+264) motifs were all shown to contribute to SCL promoter
      activity in erythroid cells, but several other motifs were not required for full
      promoter activity. The pattern of complexes binding to the +242 MAZ and +264 ETS
      sites were the same in erythroid and T cells. However, GATA-1 bound the -37 GATA
      site in erythroid cells, whereas in T cells GATA-3 was only able to bind weakly,
      if at all. Moreover, GATA-1 but not GATA-2 or GATA-3 was able to transactivate
      SCL promoter 1a in a T-cell environment. These results suggest that inactivity of
      SCL promoter 1a in T cells reflected the absence of GATA-1 rather than the
      presence of trans-dominant negative regulators.

PMID- 7632959
TI  - Expression of mdr-1 in refractory lymphoma: quantitation by polymerase chain
      reaction and validation of the assay.
AB  - Measurement of P-glycoprotein and the gene that encodes it, mdr-1, is an
      important tool for assessing the impact of multidrug resistance in clinical
      cancer. We evaluated mdr-1 expression by a quantitative polymerase chain reaction
      (PCR) assay in 78 biopsy samples from 48 patients with refractory lymphoma
      enrolled on a trial of infusional chemotherapy (EPOCH) in which R-verapamil was
      added as an antagonist of P-glycoprotein in a subset of patients whose tumors
      were unresponsive to treatment. Expression of mdr-1 was detectable in all
      biopsies at the time of enrollment on study, and a fourfold or greater increase
      in mdr-1 expression was noted in 42% of patients at the time of treatment
      failure. Expression of mdr-1 was also detectable in biopsies from patients at the
      time of diagnosis of lymphoma. An endogenous control gene, beta 2-microglobulin,
      was quantitated for normalization of the mdr-1 values. The use of beta 2
      microglobulin expression for normalization was validated in a subset of samples
      by comparing Northern blots detecting beta 2-microglobulin, beta actin, and GAPDH
      gene expression. Immunoblot analysis suggested that no major discrepancy was
      present between mRNA expression and protein level. Immunophenotyping of
      lymphomatous lymph nodes showed that infiltration of tumor cells ranged from 8%
      to 95% and of normal T cells from 1% to 83%. Expression of mdr-1 in normal T
      cells and monocytes was also shown to be low. The mdr-1 levels in patient samples
      were independent of T-cell contamination, suggesting that the presence of normal
      cells has at best a small impact on mdr-1 measurements. Expression of mdr-1 in
      lymphoma can be quantitated by PCR, and wide variations in expression can be
      observed. Increased expression in patients with refractory disease supports an
      important role for Pgp in drug resistance in lymphoma. These studies will aid in
      the design and interpretation of clinical trials in lymphoma.

PMID- 7632960
TI  - TEL and KIP1 define the smallest region of deletions on 12p13 in hematopoietic
      malignancies.
AB  - Unbalanced translocations as well as interstitial deletions of the short arm of
      chromosome 12 [del(12p)] are found as recurring chromosomal changes in a broad
      spectrum of hematopoietic malignancies. These changes result in the hemizygous
      deletion of genetic material from 12p. We mapped a yeast artificial chromosome
      containing the TEL gene, a cosmid contig containing part of TEL and a P1 contig
      containing the KIP1 gene to 12p13. These probes were used for fluorescence in
      situ hybridization to analyze samples from 47 patients with various hematologic
      malignancies who had unbalanced translocations (25 patients) leading to loss of
      12p or deletions (22 patients) involving 12p13. The patients had acute
      lymphoblastic leukemia (8 cases), myelodysplastic syndrome (MDS; 11 cases), acute
      myeloid leukemia (AML; 10 cases), myeloproliferative disorders (4 cases), therapy
      related MDS or AML (7 cases), non-Hodgkin's lymphoma (2 cases), and other
      hematopoietic malignancies (5 cases). All three probes were hemizygously detected
      in 26 cases and were completely retained in only 9 cases. In 12 cases probes for
      one of the two genes were deleted, allowing us to map the smallest region of
      overlap of these deletions to a small genomic region that is bordered on the
      telomeric side by the TEL gene and on the centromeric side by KIP1. The genomic
      distance between TEL and KIP1 is estimated to be about 1 to 2 Mbp.

PMID- 7632961
TI  - Deletions of the cyclin-dependent kinase inhibitor genes p16INK4A and p15INK4B in
      non-Hodgkin's lymphomas.
AB  - The tumor suppressor genes p16INK4A and p15INK4B map to the 9p21 chromosomal
      locus and are either homozygously deleted or mutated in a wide range of human
      cancer cell lines and tumors. Although chromosome 9 abnormalities have been
      described in non-Hodgkin's lymphomas (NHLs), to date, the mutational status of
      these genes has not been determined for these malignancies. A total of five cell
      lines and 75 NHLs were examined for homozygous deletions or point mutations in
      the coding regions of both the p15 and p16 genes using Southern blot and/or
      polymerase chain reaction-single-strand conformation polymorphism analyses.
      Homozygous deletions of either the p16 gene or both the p15 and p16 genes were
      observed in one diffuse large B-cell lymphoma cell line and two uncultured
      lymphomas consisting of one large B-cell and one mixed T-cell lymphoma. In
      contrast, point mutations were not detected in either the cell lines or
      lymphomas. These results indicate that the rate of alterations in the p15 and p16
      genes is low for lymphomas, but loss of p16 and/or p15 may be involved in the
      development of some lymphomas.

PMID- 7632964
TI  - Cell-free transmission of Fv-4 resistance gene product controlling Friend
      leukemia virus-induced leukemogenesis: a unique mechanism for interference with
      viral infection.
AB  - Fv-4 is a mouse gene that dominantly confers resistance to infection by ecotropic
      murine leukemia virus (MuLV). We previously demonstrated that mixed radiation
      bone marrow chimeras containing Fv-4r-bearing BALB/c-Fv-4Wr (C4W) bone marrow and
      Fv-4r-bearing C3H/He (C3H) bone marrow grafted into C3H recipient mice (C4W+C3H-
      >C3H) were resistant to Friend leukemia virus (FLV)-induced leukemogenesis, even
      when they contained as high as 70% C3H-derived cells. This indicates that FLV
      sensitive C3H-derived cells are rendered refractory to infection and/or
      transformation with FLV when they coexist in mice with Fv-4r-bearing cells. To
      investigate the mechanism of Fv-4 resistance to FLV-induced leukemogenesis, we
      first examined the expression of Fv-4r env antigen in the peripheral blood
      mononuclear cells (PBMC) of these chimeras. The Fv-4r env antigen was present not
      only on C4W-derived cells, but also on Fv-4r-bearing C3H-derived cells in C4W+C3H
      ->C3H mixed bone marrow chimeras. The Fv-4r env antigen that binds to the cells
      surface of C3H cells was found in sera from normal C4W mice, C4W-->C3H chimeras,
      and C4W+C3H-->C3H mixed chimeras. The serum Fv-4r env antigen binds to ecotropic
      MuLV receptors, shown by specific binding to transfectant mink cells expressing
      ecotropic MuLV receptor, but not to parental mink cells. To determine whether the
      binding of Fv-4r env antigen to the putative MuLV receptors would block FLV
      infection, C3H thymocytes or spleen cells that had been preincubated with C4W
      serum were mixed with FLV and the subsequent production of MuLV specific antigens
      was examined. C3H thymocytes or spleen cells treated with C4W serum became
      refractory to binding by FLV. These results provide evidence that the Fv-4r env
      antigen is released from C4W-derived cells in vivo and binds to cells expressing
      surface receptors for ecotropic MuLV, thereby protecting them from infection with
      FLV. The implication of these findings for gene therapy of retrovirus-induced
      disease such as acquired immune deficiency syndrome (AIDS) is discussed.

PMID- 7632962
TI  - Characterization of acute promyelocytic leukemia cases with PML-RAR alpha
      break/fusion sites in PML exon 6: identification of a subgroup with decreased in
      vitro responsiveness to all-trans retinoic acid.
AB  - Of 113 acute promyelocytic leukemia cases documented to have diagnostic PML-RAR
      alpha hybrid mRNA, 10 cases (8.8%) had fusion sites in PML gene exon 6 (V-forms)
      rather than in the two common hybrid mRNA configurations resulting from
      breaksites in either PML gene intron 6 (L-forms) or intron 3 (S-forms). In 4 V
      form cases, a common break/fusion site was discovered at PML gene nucleotide (nt)
      1685, abutting a 3' cryptic splice donor sequence. The fusion site was proximal
      to the common site in 1 case and more distal in 5 cases. The open reading frame
      encoding a PML-RAR alpha gene was consistently preserved, either by an in-frame
      fusion site or by the insertion of 3 to 127 unidentified nts. In 2 V-form cases,
      hybridization analysis of the reverse transcriptase-polymerase chain reaction
      products with a PML-RAR alpha juction probe was required for discrimination from
      L-form cases. Two V-form subgroups were defined by in vitro sensitivity to all
      trans retinoic acid (tRA)-induced differentiation: 4 of 4 cases tested with
      fusion sites at or 5' to nt 1685 (subgroup E6S) had reduced sensitivity (EC50 >
      or = 10(-7) mol/L), whereas 4 of 4 cases with fusion sites at or 3' to nt 1709
      (subgroup E6L) had high sensitivity (EC50 < 10(-8) mol/L) indistinguishable from
      that of L-form and S-form cases. These results provide the first link between PML
      RAR alpha configuration and tRA sensitivity in vitro and support the importance
      of subclassifying APL cases according to PML-RAR alpha transcript type.

PMID- 7632963
TI  - Loss of the cyclin-dependent kinase 4-inhibitor (p16; MTS1) gene is frequent in
      and highly specific to lymphoid tumors in primary human hematopoietic
      malignancies.
AB  - The cyclin-dependent kinase 4-inhibitor (CDK41; p16; or MTS1) gene has been
      proposed as a candidate for a tumor-suppressor gene located in chromosome 9p21, a
      frequently deleted region in a wide spectrum of human cancers, including
      leukemias. Recent studies disclosed that it was frequently deleted or mutated in
      a variety of primary human cancers, including acute lymphoblastic leukemia. The
      purpose of this study is to figure out the precise manners and frequencies of p16
      gene inactivation in diverse hematopoietic tumor types and thus to clarify its
      significance in development of human hematopoietic malignancies. A total of 410
      tumor specimens from patients with primary hematopoietic malignancies were
      examined for deletions of the p16 gene as well as the neighboring p15 gene and
      the nearby interferon alpha gene by Southern blot analysis. Tumor-specific
      mutations or small deletions of the p16 gene were also studied in 74 patients
      using single-strand conformation polymorphism analysis and direct sequencing.
      Loss of the p16 gene was most frequently observed among the three genes examined
      and was found in 59 of the 410 patients: 2 of 134 with acute myelocytic leukemia,
      41 of 105 with acute lymphocytic leukemia, 2 of 15 with chronic lymphocytic
      leukemia, 5 of 14 with adult T-cell leukemia, 4 of 33 with non-Hodgkin's
      lymphoma, 3 of 8 with mixed-lineage leukemia, and 2 of 61 with chronic myelocytic
      leukemia. In 16 of the 59 patients, the p16 deletions occurred due to
      rearrangements within the small region between the p15 exon 2 and the p16 exon 2.
      Tumor-specific mutations or small deletions of the p16 gene were not detected in
      the 74 patients examined, including 12 of 14 patients with hemizygous deletions
      of the gene. Loss of the p16 gene is frequent in and highly specific to lymphoid
      malignancies (54 of 183 [30%] in lymphoid tumor v2 of 219 [1%] in myeloid tumors;
      P < .0001). The deletion analyses strongly suggest that the p16 gene is a tumor
      suppressor gene located in chromosome 9p21 that is involved in development of
      human lymphoid tumors. Gene deletions but not minute mutations should be the
      predominant mechanism of p16 gene inactivation in these types of tumors.

PMID- 7632965
TI  - Influence of glutamine on the phenotype and function of human monocytes.
AB  - Reduced concentrations of glutamine (GLN) in plasma and skeletal muscle,
      defective host defense systems, and a diminished expression of the HLA-DR antigen
      on monocytes are important diagnostic parameters for late post-injury sepsis. In
      this in vitro study, we investigated whether blood monocyte-derived macrophage
      antigen expression and function from healthy donors is influenced by GLN.
      Lowering the GLN concentration in culture medium from 2 mmol/L to 200 mumol/L
      reduced the expression of HLA-DR by 40% (P < .001) on monocyte-derived
      macrophages, and decreased tetanus toxoid-induced antigen presentation. In
      addition, low GLN levels downregulated the expression of intercellular adhesion
      molecule-1 (ICAM-1/CD54), Fc receptor for IgG (Fc gamma RI/CD64), and complement
      receptors type 3 (CR3; CD11b/CD18) and type 4 (CR4; CD11c/CD18). A correlation
      was found between the phagocytosis of IgG-sensitized ox erythrocytes or opsonized
      Escherichia coli and the decreased expression of Fc gamma RI and CR3. Monocyte
      expression of CD14, CD71, and Fc gamma RIII/CD16 and capacity to phagocytose
      latex beads were not affected by altering the level of GLN. Depletion of GLN was
      associated with a significant reduction in cellular adenosine triphosphate (ATP),
      which may have influenced cell surface marker expression and phagocytosis. It
      remains to be seen whether these in vitro findings are of clinical significance
      in the treatment of sepsis.

PMID- 7632966
TI  - Regulation of ferritin H-chain expression in differentiating Friend leukemia
      cells.
AB  - The mechanisms that regulate the expression of ferritin, the iron storage
      protein, have been investigated in Friend erythroleukemia cells (FLCs) induced to
      differentiate by several chemical compounds. In differentiating FLCs,
      administration of hemin increases the steady-state level of ferritin mRNA about
      15-fold and the ferritin content about 20- to 25-fold. Conversely, iron salts
      have only mild stimulatory effects on these parameters and iron chelators only
      slightly inhibited the stimulatory effect of hemin. Transient transfection
      experiments with a construct in which the human ferritin H-chain promoter drives
      the expression of the indicator chloramphenicol acetyltransferase (CAT) gene show
      that the increase in mRNA content is mainly due to enhanced transcription. In
      addition to transcriptional effects, translational regulation resulting in the
      further increase in ferritin synthesis is shown by CAT assays from cells
      transiently transfected with a construct containing the coding region for the
      indicator CAT mRNA under the translational control of the mRNA ferritin iron
      responsive element. We conclude that, in FLCs induced to differentiate, hemin
      acts synergistically with the differentiation inducers, increasing ferritin
      expression. Both transcriptional and translational mechanisms are responsible for
      this synergistic effect, which appears to be characteristic of differentiated
      erythroid cells because it is not observed in other cell types (ie, fibroblastic
      cell lines).

PMID- 7632967
TI  - Reverse dot-blot detection of the African-American beta-thalassemia mutations.
AB  - DNA-based diagnosis of the beta thalassemias provides accuracy to newborn
      screening genetic counseling, and prenatal diagnosis. However, the use of
      polymerase chain reaction (PCR)-based methods is challenged by the great number
      of different-beta-thalassemia mutations that exist even within defined ethnic
      groups. In this regard, the reverse dot-blot method offers a means of screening
      for several mutations with a single hybridization reaction. We have applied the
      reverse dot-blot method to the detection of the beta-thalassemia mutations of
      African-Americans. We used two biotin-labeled primer pairs in a duplex reaction
      to amplify and label two beta-globin target DNA fragments that encompass all
      known African-American beta-thalassemia mutations. The PCR products were
      denatured and hybridized to polyT-tailed, membrane-fixed, allele-specific probe
      pairs for the hemoglobin (Hb) S, Hb C, and 14 beta-thalassemia mutations and
      their corresponding wild-type sequences. Seven common mutations plus Hb S and Hb
      C were included on one diagnostic strip, and seven less common beta-thalassemia
      mutations were included on another strip. Carefully controlled, high stringency
      hybridization allowed accurate distinction of these alleles. Reverse dot-blot
      diagnosis of the less common beta-thalassemia mutations precludes the need for
      alternative, more technically challenging methods. This method provides a rapid,
      accurate method for diagnosis of beta thalassemia among African-Americans and
      other ethnic groups in which beta thalassemia occurs.

PMID- 7632969
TI  - Shape response of human erythrocytes to altered cell pH.
AB  - Alteration of red blood cell (RBC) pH produces stomatocytosis (at low pH) and
      echinocytosis (at high pH). Cell shrinkage potentiates high pH echinocytosis, but
      shrinkage alone does not cause echinocytosis. Mechanisms for these shape changes
      have not been described. In this study, measured dependence of RBC shape on cell
      pH was nonlinear, with a broad pH range in which normal discoid shape was
      maintained. Transbilayer distribution of phosphatidylcholine and
      phosphatidylserine, measured by back-extraction of radiolabeled lipid, was the
      same in control and altered pH cells. Possible roles of pH-titratable inner
      monolayer phospholipids were examined by assessing pH-dependent shape in cells in
      which their levels had been perturbed. In metabolically depleted cells and
      calcium-treated cells, which have altered levels of phosphatidic acid,
      phosphatidylinositol-4-phosphate, and/or phosphatidylinositol-4,5-bisphosphate,
      low cell pH was stomatocytogenic and high cell pH was echinocytogenic, as in
      control cells. Thus, neither change in membrane lipid asymmetry nor normal levels
      of the pH-titratable inner monolayer lipids is necessary for cell pH-mediated
      shape change.

PMID- 7632970
TI  - The significance of HLA-DRB1 matching on clinical outcome after HLA-A, B, DR
      identical unrelated donor marrow transplantation.
AB  - Despite matching for serologically defined HLA-A, B, DR antigens, acute graft
      versus-host disease (GVHD) is a major complication contributing to increased
      morbidity and mortality in patients who undergo marrow transplantation from
      unrelated donors. The extent to which unrecognized mismatching for alleles that
      encode DR1-DR18 contribute to the increased risk of acute GVHD and overall
      survival is unknown. We analyzed 364 patients and their HLA-A, B, DR
      serologically matched donors to determine whether molecular typing of DRB1
      alleles can allow more accurate donor/recipient matching and thereby improve
      clinical outcome after marrow transplantation. DRB1 alleles were typed by
      sequence-specific oligonucleotide probe hybridization methods. Selected alleles
      were confirmed by DNA sequencing. Of the 364 pairs, 305 were matched and 59 were
      mismatched for DRB1. The probability of moderate to severe acute GVHD was .48 for
      the matched and .70 for the mismatched patients. Compared with mismatched
      patients, the estimated relative risk (RR) of GVHD for matched patients was .58
      (95% confidence interval [CI], .40 to .85). DRB1 matching decreased the risk of
      transplant-related mortality (RR, .66; 95% CI, .44 to .97) and was associated
      with decreased overall mortality (RR, .71; 95% CI, .51 to 1.0). Therefore,
      matching DRB1 alleles of the donor and recipient decreases the risk of acute GVHD
      and improves survival after unrelated marrow transplantation. These results
      indicate that prospective matching of patients and donors for DRB1 alleles is
      warranted.

PMID- 7632968
TI  - Molecular basis and expression of the LWa/LWb blood group polymorphism.
AB  - The Landsteiner-Wiener (LW) blood group antigens reside on a 42-kD erythrocyte
      membrane glycoprotein that has recently been cloned. Here, we found that the
      molecular basis for the LWa/LWb polymorphism is determined by a single base pair
      mutation (A308G) that correlates with a Pvu II restriction site and results in a
      Gln70Arg amino acid substitution. COS-7 cells transfected with LWa or LWb cDNAs
      reacted with human anti-LWa and anti-LWb sera, respectively, as well as with a
      murine monoclonal anti-LWab antibody, as shown by flow cytometry analysis.
      Moreover, a 42-kD protein was immunoprecipitated from the transfected cells with
      the monoclonal anti-LWab antibody. These findings indicate that LWa and LWb are
      alleles of the LW blood group locus as defined also by a monoclonal anti-LWab of
      nonhuman origin. In addition, the LW locus has been assigned to chromosome
      19p13.3 by in situ hybridization. Study by Southern blot analysis indicated also
      that the LW locus is composed of a single gene that was not grossly rearranged in
      rare LW(a-b-) and Rhnull individuals deficient for LW antigens. In addition, Pvu
      II restriction fragment-length polymorphism analysis indicated that these
      variants were all homozygous for a phenotypically silent LWa allele.

PMID- 7632971
TI  - Long-term effects of hepatitis C virus infection in allogeneic bone marrow
      transplant recipients.
AB  - A total of 161 patients transplanted between 1978 and 1991 and who had survived
      at least 2 years after allogeneic bone marrow transplantation (BMT) were studied.
      Of 161 surviving patients, 28 (17.4%) were positive for hepatitis C virus (HCV)
      either by serology or polymerase chain reaction (PCR). Twenty-five patients were
      positive for HCV RNA by PCR, and 26 of the 28 patients had HCV antibodies
      detected by enzyme-linked immunosorbent assay (ELISA). The median follow-up time
      of HCV-positive patients was 6.1 years (range, 2.8 to 14.0 years). There was no
      difference in the frequency or degree of liver dysfunction between patients who
      were PCR-positive or -negative before BMT. Six patients developed severe liver
      dysfunction after BMT, and five of these patients did so after discontinuation or
      tapering of immunosuppression. No patient has developed liver failure. Serum
      transaminases were abnormal at the time of last follow up in 19 of 28 (68%)
      patients. Fifteen patients have had liver biopsies. No biopsy showed development
      of cirrhosis. We conclude that HCV is not a major contributing factor to
      morbidity and mortality during the first 5 to 10 years after allogeneic BMT.

PMID- 7632972
TI  - Consolidation treatment of adult acute lymphoblastic leukemia: a prospective,
      randomized trial comparing allogeneic versus autologous bone marrow
      transplantation and testing the impact of recombinant interleukin-2 after
      autologous bone marrow transplantation. BGMT Group.
AB  - A prospective, randomized trial was initiated in adult acute lymphoblastic
      leukemia (ALL) to compare (1) disease-free survival (DFS) after allogeneic or
      autologous bone marrow transplantation (BMT) and (2) the relapse rate of patients
      treated with or without interleukin-2 (IL-2) after autologous BMT. A total of 135
      previously untreated patients, aged under 55 years, received the Berlin-Frankfurt
      Muster (BFM) induction regimen: 126 patients (93%), of which 120 were HLA-typed,
      achieved complete remission (CR). According to this genetic randomization,
      patients with (n = 43) or without an HLA-identical sibling (n = 77) were to
      receive allogeneic or autologous BMT, respectively. The 3-year post-CR
      probability of DFS was significantly higher in the HLA-identical sibling group
      than in the non-HLA-identical sibling group (68% v 26%; P < .001). Eligible
      patients were randomized to receive (n = 30) or not to receive (n = 30) IL-2
      after autologous BMT: the 3-year post-BMT probability of continuous CR was
      similar in both groups (29% v 27%, respectively). We conclude that, in ALL, early
      allogeneic BMT after the BFM induction regimen is an effective consolidation
      treatment and that IL-2 does not decrease the high relapse rate observed after
      autologous BMT.

PMID- 7632973
TI  - Results of allogeneic bone marrow transplantation in patients with leukocyte
      adhesion deficiency.
AB  - We have retrospectively analyzed the outcome of bone marrow transplantation (BMT)
      in 14 patients with leukocyte adhesion deficiency (LAD) performed in two centers
      between 1981 and 1993. Five patients received BMT from HLA-identical donors. Nine
      received T-depleted marrow from two HLA antigen- or haplotype-incompatible
      parents. Conditioning regimen consisted of chemotherapy exclusively in 13
      patients and associated with total body irradiation (TBI) in one patient. In five
      cases, failure of engraftment occurred as a result of either insufficient
      myeloablation (n = 3) or, possibly, graft rejection in two cases of moderate
      phenotype of LAD. The second conditioning regimen consisted of TBI and
      chemotherapy with the use of anti-lymphocyte function-associated antigen 1 (LFA
      1) and anti-CD2 monoclonal antibodies for patients with the moderate phenotype of
      LAD. These patients were successfully retransplanted. Eight patients developed
      acute graft-versus-host disease (GVHD). Chronic GVHD occurred in five cases. GVHD
      led to the death of three patients. Ten patients are alive and well 12 months to
      12 years after BMT. Chimerism is full in six of these patients and mixed but
      stable in four with variable proportion of donor leukocytes. One patient with
      less than 15% donor leukocytes has mild gingivitis, while the others are well.
      Sequelae from BMT are limited in two cases to growth retardation caused by TBI.
      Success of BMT in cases of LAD including seven of nine recipients of HLA
      nonidentical marrow indicates that this procedure can be proposed as a curative
      approach to LAD regardless of an available HLA-identical donor. Great care should
      be taken in GVHD prophylaxis and treatment.

PMID- 7632975
TI  - Thrombopoietin and neurotrophins share a common domain.

PMID- 7632974
TI  - Unrelated donor bone marrow transplantation: influence of HLA A and B
      incompatibility on outcome.
AB  - We have studied the outcome of 211 consecutive unrelated donor (URD) bone marrow
      transplants (BMT) performed at the University of Minnesota (Minneapolis, MN)
      between May 1985 and December 1992. Ninety patients (43%) received marrow matched
      serologically at HLA A, B, and DR loci; 86 (41%) received marrow with a major and
      32 (15%) marrow with a minor serologic mismatch at the HLA A or B locus.
      Multivariate analysis revealed that older age had an adverse effect on survival.
      In younger (age less than 18 years) recipients, survival after fully matched (A,
      B, and DR sub-type) or major mismatched (A or B locus), DR subtype-matched donor
      BMT was not significantly different (P = .4; survival: 53% v 41%, respectively,
      at 3 years). For adults, survival after matched donor BMT was significantly
      better than that with mismatched donors (P < .01; survival: 30% v 10%,
      respectively, at 3 years). Formal quality of life assessment by telephone
      interview demonstrated similar functional status in survivors of URD and related
      donor (RD) BMT at least 2 years post-BMT. URD BMT provides effective therapy for
      a variety of lethal hematopoietic diseases that rivals outcome of RD transplant
      in some cases. Use of URD marrow with a major mismatch at one HLA A or B locus is
      well tolerated in young, but not in older, recipients. These observations should
      be used to improve donor selection and counseling for URD BMT candidates.

PMID- 7632976
TI  - All-trans retinoic acid for the treatment of newly diagnosed acute promyelocytic
      leukemia.

PMID- 7632977
TI  - Does unusual entrainment of the circadian system under T36h photocycles reduce
      the critical daylength for photoperiodic induction in Japanese quail?
AB  - In photoperiodic species, short daylength resonance cycles of modulo t + 1/2 (t =
      24 h) behave like long days because they entrain the circadian system so that
      alternate light pulses coincide with the photoinducible phase (Oi) in castrated
      quail. However, while a long-day response after exposure to a single long
      daylength is readily detected by a rise in plasma LH (photoinduction), long-term
      exposure to LD 6:30 is ineffective in this respect. To discover whether this
      occurs because of unusual entrainment, circadian rhythms in quail and starlings
      were investigated. Whereas starlings entrained in the expected way with alternate
      pulses falling at different circadian phases, activity bouts in quail appeared to
      follow 24 h after successive light pulses. Because of this, activity was examined
      in free-running conditions to confirm that the pacemaker in quail was indeed
      being reset to a constant phase (reset to circadian time [CT] 0) by successive
      pulses. Examination of the circadian rhythms of plasma melatonin secretion under
      LD 6:30 also showed a resetting to CT 0. The positioning of all light pulses at
      the same circadian phase in the early subjective day explains the lack of
      photoinduction in quail since Oi in the early subjective night phase remains
      unilluminated. A second feature in quail is that when the length of the
      photophase is gradually increased within T36h cycles, there is a progressive
      increase in the degree of photoinduction although the photophase length remains
      well below the critical daylength for induction in normal T24h cycles. We
      therefore tested whether Oi is reset to a constant phase by successive pulses in
      LD 6:30, and that this phase is also advanced relative to light onset so that
      photophases shorter than the critical daylength can interact with Oi to cause
      induction. Such a reduction in critical daylength relative to successive LD 6:30
      pulses was confirmed by transferring quail to various types of long day and
      measuring the change in LH secretion. When the long-day test was replaced with
      continuous light, stimulation of LH secretion occurred 5-7 h earlier in quail
      pretreated with LD 6:30 and LD 6:54 compared to quail pretreated with LD 6:18 or
      LD 6:42, implying that Oi had been markedly phase advanced under resonance cycle.

PMID- 7632978
TI  - Long-term reproductive effects of a single long day in the Siberian hamster
      (Phodopus sungorus).
AB  - Testicular regression was prevented or attenuated in Siberian hamsters exposed to
      a single 1- to 4-h extension of the 16-h photophase at 18 days of age and
      subsequently maintained in a short photoperiod (8L:16D) through Day 35.
      Testicular weights on Day 35 were not correlated with the duration of the active
      phase of wheel running or with the time of activity onset after transfer to the
      8L:16D photoperiod. Wheel-running activity was not stably entrained to the light
      dark cycle by 35 days of age. Progonadal effects of a single 33-h light pulse
      were greatest at 18 days of age, still evident at 30 days, but undetectable in
      older hamsters. In female hamsters, a single longer day at weaning was associated
      with increased fecundity several weeks later. Long photoperiods accelerated
      development of antral ovarian follicles, but exposure to males was necessary to
      induce ovulation before 60 days of age. The interval beginning shortly after
      weaning is one of heightened responsiveness to changes in day length (DL);
      exposure to increasing DL at this time may prolong the breeding season when DL
      decreases after the summer solstice. We suggest that the long-term effects of
      acute light treatments on reproduction are mediated by sustained changes in
      melatonin secretion induced by reprogramming of circadian oscillators.

PMID- 7632979
TI  - Light-induced phase shifts in onset and offset of running-wheel activity in the
      Syrian hamster.
AB  - The effects of light pulses on activity onset and offset were assessed in
      intergeniculate leaflet- and ventral lateral geniculate nucleus-lesioned Syrian
      hamsters with a precise onset and offset of circadian wheel-running activity.
      Light pulses applied to animals in constant darkness during the early subjective
      night induced phase delays in both activity onset and offset, while light pulses
      during the late subjective night induced phase advances in the onset and offset
      of activity. Despite the fact that the direction of onset and offset shifts were
      similar, differences were found in the magnitude of light-induced phase shifts.
      Steady state phase delays were larger in the activity onset, while steady state
      phase advances were largest in the offset of activity. We found phase delays and
      phase advances within one cycle after the presentation of a light pulse in both
      activity onset and offset. Differences in magnitude of these immediate phase
      shifts in activity onset and offset resulted in a compression of activity time
      for a number of cycles following a light pulse. Similar results were obtained in
      a selected group of intact animals indicating that intergeniculate leaflet- and
      ventral lateral geniculate nucleus-lesioned hamsters provide a good model to
      investigate the effects of light on circadian onset and offset of running-wheel
      activity.

PMID- 7632980
TI  - Circannual alterations in the circadian rhythm of melatonin secretion.
AB  - To determine if a circadian rhythm known to be functionally related to the
      reproductive axis varies on a circannual basis, we monitored the circadian
      secretion of melatonin at monthly intervals for 2 years in four ovariectomized,
      estradiol-implanted ewes held in a constant short-day photoperiod. Prior to the
      study, ewes had been housed in a short-day (8L:16D) photoperiod for 4 years and
      were exhibiting circannual reproductive rhythms as assessed by serum luteinizing
      hormone (LH) levels. Three of the four sheep showed unambiguous deviations from
      the expected nocturnal melatonin secretion at two different times approximately 1
      year apart. Nocturnal rises in melatonin, which usually last the duration of the
      dark phase, were delayed by 3-14 h or were missing. Altogether, five of the seven
      melatonin alterations observed in these three ewes occurred during the nadir of
      the circannual LH cycle. In the remaining ewe, we did not observe an altered
      melatonin secretory pattern during this period, and this ewe also failed to show
      a high amplitude circannual cycle of LH. The results provide evidence for a
      circannual change in the circadian rhythm of melatonin secretion. This alteration
      in melatonin secretion may serve as a "functional" change in daylength, and
      thereby may influence the expression of the circannual reproductive rhythm of
      sheep held in a fixed photoperiod for an extended time.

PMID- 7632981
TI  - Light control of the duration of the daily melatonin signal under long and short
      days in the Soay ram. Role of inhibition and entrainment.
AB  - Light acts in two ways to control the duration of the nocturnal melatonin rhythm.
      It inhibits the production of melatonin from the pineal gland and it entrains the
      underlying circadian rhythm generators located in the suprachiasmatic nuclei. To
      investigate the role of these two mechanisms under long and short days, four
      experiments were carried out using groups of adult Soay rams (n = 6-8). The
      animals were housed in individual pens in light-controlled rooms and entrained to
      long (LD 16:8) or short (LD 8:16) days for at least 8 wk. The treatments were as
      follows: (i) dark period extended by 4 h under long days (L dark-delay), (ii)
      dark period advanced by 4 h under long days (L dark-advance), (iii) dark period
      extended by 4 h under short days (S dark-delay), and (iv) dark period advanced by
      4 h under short days (S dark-advance). Each treatment was given on a single day
      and the animals were subsequently maintained in, or transferred to, constant dim
      red light (DD) for 24 h. A control group (C) was run in parallel with each
      treatment group. Blood samples were collected every 30 min for 6-9 h during the
      dark-shift to monitor the light-induced changes in the secretion of melatonin,
      and during DD to monitor any phase shift in the endogenous rhythm (phase markers
      provided by onset or offset of melatonin secretion). L dark-delay resulted in a
      significantly (p < 0.01, ANOVA) later offset of the melatonin peak (3.4-h delay)
      with no phase shift of the onset of the rhythm under DD.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7632983
TI  - Tryptophan loading modulates light-induced responses in the mammalian circadian
      system.
AB  - Enhanced endogenous serotonergic activity, stimulated by L-tryptophan (TRYPT)
      loading, was found to have a substantial impact on neurochemical and behavioral
      aspects of the circadian response to light in the male Syrian hamster. An
      intraperitoneal (i.p.) injection of 150 mg/kg TRYPT significantly stimulated
      serotonin (5-HT) release in the suprachiasmatic nuclear (SCN) region, as
      reflected by a 205 +/- 30% maximal increase in the extracellular concentration of
      5-HT assessed using microdialysis. Administration of TRYPT 1 h before exposure to
      a light pulse (30 min, 40 lux) delivered during late subjective night dose
      dependently suppressed the number of SCN cells expressing light-induced Fos-like
      immunoreactivity (Fos-LI; maximal suppression @200 mg/kg was 77 +/- 4%, p <
      0.001). This action of TRYPT was attenuated by pretreatment with the 5-HT1a
      antagonist, NAN-190, and was abolished by the 5-HT2/5-HT7 antagonist, ritanserin,
      or the nonselective 5-HT antagonist, metergoline (all 10 mg/kg). These
      antagonists alone had no effect on light-induced Fos. In a second experiment,
      pretreatment of free-running hamsters housed under constant darkness with 150
      mg/kg TRYPT 45-60 min prior to light exposure (10 min, 20 lux) during late
      subjective night (CT 19) significantly attenuated the light-induced phase
      advances of the circadian activity rhythm (66 +/- 7 min vs. 100 +/- 6 min for
      vehicle controls; p < 0.001). The same dose of TRYPT given 1 h before lights-on
      for 5 consecutive days in hamsters maintained under 14L:10D altered the phase
      angle of entrainment such that activity onsets were delayed by 36 +/- 8 min
      relative to controls (p < 0.05). The same dose of TRYPT administered during late
      subjective night also suppressed the extracellular concentration of glutamate in
      the SCN region assessed using microdialysis (55 +/- 8% suppression; p < 0.05 vs.
      baseline). These results support the hypothesis that the ascending serotonergic
      projection to the SCN modulates photic entrainment processes within the circadian
      oscillator.

PMID- 7632982
TI  - The pineal gland: photoreception and coupling of behavioral, metabolic, and
      cardiovascular circadian outputs.
AB  - Although removal of the pineal gland has been shown to have very little effect on
      the mammalian circadian system in constant darkness (DD), several recent reports
      have suggested that the mammalian pineal gland may be more important for
      circadian organization in nocturnal rodents than was previously believed. Removal
      of the pineal gland (PINX) facilitates the disruptive effects of constant bright
      light on wheel-running rhythmicity. This suggests at least two possibilities for
      the role of the pineal gland in the mammalian circadian system. First,
      pinealectomized rats may perceive ambient light intensity to be brighter than do
      sham-operated (SHAM) rats. Second, the pineal gland, probably via its secretion
      of melatonin, may also be involved in coupling components of the circadian
      system. Coupling, as we see it, may occur at several levels of organization: (1)
      between retinohypothalamic afferents and suprachiasmatic nuclei (SCN) oscillatory
      neurons, (2) among multiple SCN oscillators, (3) between the SCN and their
      multiple outputs, and/or (4) among the multiple circadian outputs themselves. In
      this study we show that PINX rats free-run with a longer period in four different
      light intensities than do SHAM rats. Moreover, the rate of increase of tau is
      greater among PINX rats than among SHAM rats. This supports the first hypothesis.
      We also show that in PINX rats the circadian rhythms of wheel running, general
      activity, body temperature, and heart rate are all more disrupted in constant
      bright light than are those of SHAM rats, and each rhythmic output is disrupted
      in parallel. This supports the second hypothesis. Melatonin is probably not
      involved in coupling presynaptic elements of SCN afferents in the
      retinohypothalamic tract to pacemaking cells within the SCN, since enucleation
      has no effect on SCN 2-[125I]iodomelatonin (IMEL) binding. Together the data do
      not discount either of the two hypotheses but do restrict the possible levels at
      which the pineal gland is involved in coupling. These data also further support a
      growing body of literature indicating that the pineal gland and its hormone
      melatonin play a role in mammalian circadian organization.

PMID- 7632984
TI  - Light treatment for sleep disorders: consensus report. I. Chronology of seminal
      studies in humans.
AB  - Examination of the influence of the light-dark cycle on circadian rhythmicity has
      been a fundamental aspect of chronobiology since its inception as a scientific
      discipline. Beginning with Bunning's hypothetical phase response curve in 1936,
      the impact of timed light exposure on circadian rhythms of literally hundreds of
      species has been described. The view that the light-dark cycle was an important
      zeitgeber for the human circadian system, as well, seemed to be supported by
      early studies of blind and sighted subjects. Yet, by the early 1970s, based
      primarily on a series of studies conducted at Erling-Andechs, Germany, the notion
      became widely accepted that the light-dark cycle had only a weak influence on the
      human circadian system and that social cues played a more important role in
      entrainment. In 1980, investigators at the National Institute of Mental Health
      reported that bright light could suppress melatonin production in humans, thereby
      demonstrating unequivocally the powerful effects of light on the human central
      nervous system. This finding led directly to the use of timed bright light
      exposure as a tool for the study and treatment of human circadian rhythms
      disorders.

PMID- 7632985
TI  - Light treatment for sleep disorders: consensus report. II. Basic properties of
      circadian physiology and sleep regulation.
AB  - The rationale for the treatment of sleep disorders by scheduled exposure to
      bright light in seasonal affective disorder, jet lag, shift work, delayed sleep
      phase syndrome, and the elderly is, in part, based on a conceptual framework
      developed by nonclinical circadian rhythm researchers working with humans and
      other species. Some of the behavioral and physiological data that contributed to
      these concepts are reviewed, and some pitfalls related to their application to
      bright light treatment of sleep disorders are discussed. In humans and other
      mammals the daily light-dark (LD) cycle is a major synchronizer responsible for
      entrainment of circadian rhythms to the 24-h day, and phase response curves
      (PRCs) to light have been obtained. In humans, phase delays can be induced by
      light exposure scheduled before the minimum of the endogenous circadian rhythm of
      core body temperature (CBT), whereas phase advances are induced when light
      exposure is scheduled after the minimum of CBT. Since in healthy young subjects
      the minimum of CBT is located approximately 1 to 2 h before the habitual time of
      awakening, the most sensitive phase of the PRC to light coincides with sleep, and
      the timing of the monophasic sleep-wake cycle itself is a major determinant of
      light input to the pacemaker. The effects of light are mediated by the
      retinohypothalamic tract, and excitatory amino acids play a key role in the
      transduction of light information to the suprachiasmatic nuclei. LD cycles have
      direct "masking" effects on many variables, including sleep, which complicates
      the assessment of endogenous circadian phase and the interpretation of the
      effects of light treatment on sleep disorders. In some rodents motor activity has
      been shown to affect circadian phase, but in humans the evidence for such a
      feedback of activity on the pacemaker is still preliminary. The endogenous
      circadian pacemaker is a major determinant of sleep propensity and sleep
      structure; these, however, are also strongly influenced by the prior history of
      sleep and wakefulness. In healthy young subjects, light exposure schedules that
      do not curtail sleep but induce moderate shifts of endogenous circadian phase
      have been shown to influence the timing of sleep and wakefulness without markedly
      affecting sleep structure.

PMID- 7632986
TI  - Light treatment for sleep disorders: consensus report. III. Alerting and
      activating effects.
AB  - In addition to the well-established phase-shifting properties of timed exposure
      to bright light, some investigators have reported an acute alerting, or
      activating, effect of bright light exposure. To the extent that bright light
      interventions for sleep disturbance may cause subjective and/or central nervous
      system activation, such a property may adversely affect the efficacy of
      treatment. Data obtained from patient samples and from healthy subjects generally
      support the notion that exposure to bright light may be associated with enhanced
      subjective alertness, and there is limited evidence of objective changes (EEG,
      skin conductance levels) that are consistent with true physiological arousal.
      Such activation appears to be quite transient, and there is little evidence to
      suggest that bright light-induced activation interferes with subsequent sleep
      onset. Some depressed patients, however, have experienced insomnia and hypomanic
      activation following bright-light exposure.

PMID- 7632987
TI  - Light treatment for sleep disorders: consensus report. IV. Sleep phase and
      duration disturbances.
AB  - Advanced and delayed sleep phase disorders, and the hypersomnia that can
      accompany winter depression, have been treated successfully by appropriately
      timed artificial bright light exposure. Under entrainment to the 24-h day-night
      cycle, the sleep-wake pattern may assume various phase relationships to the
      circadian pacemaker, as indexed, for example, by abnormally long or short
      intervals between the onset of melatonin production or the core body temperature
      minimum and wake-up time. Advanced and delayed sleep phase syndromes and non-24-h
      sleep-wake syndrome have been variously ascribed to abnormal intrinsic circadian
      periodicity, deficiency of the entrainment mechanism, or--most simply--patterns
      of daily light exposure insufficient for adequate phase resetting. The timing of
      sleep is influenced by underlying circadian phase, but psychosocial constraints
      also play a major role. Exposure to light early or late in the subjective night
      has been used therapeutically to produce corrective phase delays or advances,
      respectively, in both the sleep pattern and circadian rhythms. Supplemental light
      exposure in fall and winter can reduce the hypersomnia of winter depression,
      although the therapeutic effect may be less dependent on timing.

PMID- 7632988
TI  - Light treatment for sleep disorders: consensus report. V. Age-related
      disturbances.
AB  - Sleep maintenance insomnia is a major complaint among the elderly. As a result,
      an inordinate proportion of sleeping pill prescriptions go to individuals over 65
      y of age. Because of the substantial problems associated with use of hypnotics in
      older populations, efforts have been made to develop nondrug treatments for age
      related sleep disturbance, including timed exposure to bright light. Such bright
      light treatments are based on the assumption that age-related sleep disturbance
      is the consequence of alterations in the usual temporal relationship between body
      temperature and sleep. Although studies are limited, results strongly suggest
      that evening bright light exposure is beneficial in alleviating sleep maintenance
      insomnia in healthy elderly subjects. Less consistent, but generally positive,
      findings have been reported with regard to bright light treatment of sleep and
      behavioral disturbance in demented patients. For both groups, it is likely that
      homeostatic factors also contribute to sleep disturbance, and these may be less
      influenced by bright light interventions.

PMID- 7632989
TI  - Light treatment for sleep disorders: consensus report. VI. Shift work.
AB  - The unhealthy symptoms and many deleterious consequences of shift work can be
      explained by a mismatch between the work-sleep schedule and the internal
      circadian rhythms. This mismatch occurs because the 24-h zeitgebers, such as the
      natural light-dark cycle, keep the circadian rhythms from phase shifting to align
      with the night-work, day-sleep schedule. This is a review of studies in which the
      sleep schedule is shifted several hours, as in shift work, and bright light is
      used to try to phase shift circadian rhythms. Phase shifts can be produced in
      laboratory studies, when subjects are kept indoors, and faster phase shifting
      occurs with appropriately timed bright light than with ordinary indoor (dim)
      light. Bright light field studies, in which subjects live at home, show that the
      use of artificial nocturnal bright light combined with enforced daytime dark
      (sleep) periods can phase shift circadian rhythms despite exposure to the
      conflicting 24-h zeitgebers. So far, the only studies on the use of bright light
      for real shift workers have been conducted at National Aeronautics and Space
      Administration (NASA). In general, the bright light studies support the idea that
      the control of light and dark can be used to overcome many of the problems of
      shift work. However, despite ongoing practical applications (such as at NASA),
      much basic research is still needed.

PMID- 7632990
TI  - Light treatment for sleep disorders: consensus report. VII. Jet lag.
AB  - Sleep disturbances are an all-too-familiar symptom of jet lag and a prime source
      of complaints for transmeridian travelers and flight crews alike. They are the
      result of a temporary loss of synchrony between an abruptly shifted sleep period,
      timed in accordance with the new local day-night cycle, and a gradually
      reentraining circadian system. Scheduled exposure to bright light can, in
      principle, alleviate the symptoms of jet lag by accelerating circadian
      reentrainment to new time zones. Laboratory simulations, in which sleep time is
      advanced by 6 to 8 h and the subjects exposed to bright light for 3 to 4 h during
      late subjective night on 2 to 4 successive days, have not all been successful.
      The few field studies conducted to date have had encouraging results, but their
      applicability to the population at large remains uncertain due to very limited
      sample sizes. Unresolved issues include optimal times for light exposure on the
      first as well as on subsequent treatment days, whether a given, fixed, light
      exposure time is likely to benefit a majority of travelers or whether light
      treatment should be scheduled instead according to some individual circadian
      phase marker, and if so, can such a phase marker be found that is both practical
      and reliable.

PMID- 7632991
TI  - Should people do unto others as they would not want done unto themselves?

PMID- 7632992
TI  - The best-interest standard: surrogate decision making and quality of life.

PMID- 7632993
TI  - Impossible choices: when patients and careproviders face impossible decisions.

PMID- 7632994
TI  - Revising the substituted judgment standard.

PMID- 7632995
TI  - Time and language in bioethics: when patient and proxy appear to disagree.

PMID- 7632996
TI  - Futility and bargaining power.

PMID- 7632997
TI  - Pain relief for dying persons: dealing with physicians' fears and concerns.

PMID- 7632998
TI  - Physician aid in dying and the relief of patients' suffering: physicians'
      attitudes regarding patients' suffering and end-of-life decisions.

PMID- 7632999
TI  - Physicians' ethical responsibilities under co-pay insurance: should potential
      fiscal liability become part of informed consent?

PMID- 7633000
TI  - Religion, race, and reason: the case of LJ.

PMID- 7633001
TI  - LJ's religous craziness.

PMID- 7633002
TI  - The fiction of neutrality.

PMID- 7633003
TI  - An algorithm for determining best interest?

PMID- 7633004
TI  - Recognizing and respecting family judgment.

PMID- 7633005
TI  - The hermeneutical process and clinical ethics.

PMID- 7633006
TI  - Some thoughts on AIDS and death.

PMID- 7633007
TI  - Legal trends in bioethics.

PMID- 7633008
TI  - Attitudes of seriously ill patients toward treatment that involves high costs and
      burdens on others.

PMID- 7633010
TI  - Relationship between the administration of selected medications and falls in
      hospitalized elderly patients.
AB  - OBJECTIVE: To examine the relationship between administration of selected
      medications and falls experienced by hospitalized elderly patients.
      Benzodiazepines and other medications previously associated with falls in elderly
      patients residing in the community and nursing homes were the primary focus.
      DESIGN: Retrospective case control. SETTING: Private, not-for-profit, 575-bed
      acute care hospital. PARTICIPANTS: A total of 100 patients who had fallen and 100
      control patients, aged at least 70 years, admitted during the same 17-month time
      period. MAIN OUTCOME MEASURES: We examined the relationship between falls and
      patient demographics, underlying disease states, number of concurrent disease
      states, and length of hospitalization. Possible associations between the
      administration of narcotics, benzodiazepines, antidepressants, antipsychotics,
      other sedating agents, antihypertensives, diuretics, nitrates, and digoxin 48
      hours prior to the fall or reference day were explored. The relationships between
      benzodiazepine half-life, dosage, administration frequency, cumulative dose, and
      falls were also examined. RESULTS: Demographically the groups were similar except
      that patients who had fallen were hospitalized significantly longer (mean 18.8 vs
      12.2 d; p < 0.00001) than control patients. Benzodiazepines were received by more
      (40% vs 20%, odds ratio = 2.67) patients who had fallen than control patients.
      The use of long (> 24 h) half-life benzodiazepines was similar in patients who
      had fallen (48%) and control patients (45%). Long half-life benzodiazepines were
      commonly administered (65%) to patients who had fallen in doses greater than that
      recommended for the elderly. Benzodiazepine use, expressed as milligrams of
      diazepam equivalents received during the 48-hour study, was higher in patients
      who had fallen than in control patients (15.00 +/- 17.80 vs 9.73 +/- 6.58 mg),
      but this was not statistically significant (p = 0.1030). Congestive heart failure
      (37% vs 24%), digoxin therapy (35% vs 22%), or administration of 3 or more
      psychoactive agents (17% vs 4%) were all more common in patients who had fallen
      than in control patients. CONCLUSIONS: Falls experienced by the elderly patients
      in our acute care institution were associated with the presence of congestive
      heart failure along with digoxin therapy, benzodiazepine use, or the use of at
      least 3 psychoactive agents.

PMID- 7633011
TI  - Medication taking behaviors in the high- and low-functioning elderly: MacArthur
      field studies of successful aging.
AB  - OBJECTIVE: To describe and compare medication-taking behaviors in the high- and
      low-functioning elderly living in the community. DESIGN: A cross-sectional design
      with data collected by interview. SETTING: The study included 5 counties in the
      southern Piedmont area of North Carolina. PARTICIPANTS: Respondents included 242
      elderly aged 70-79 years selected from the Piedmont Health Survey of the Elderly
      and the MacArthur Research Program on Successful Aging. MAIN OUTCOME MEASURES:
      Outcome measures included strategies used to remember to take drugs, reasons
      given for skipping medications, factors associated with understanding of drugs,
      the number of over-the-counter and prescribed drugs used, and the number of drugs
      used in therapeutic categories. RESULTS: Low-functioning elderly white
      respondents took greater numbers of prescribed drugs than did blacks or high
      functioning whites. Respondents had a better understanding of prescribed than of
      over-the-counter drugs, with the poorest understanding of nutritional
      supplements. Men and blacks had poorer understanding of drugs than women and
      whites. The strategies subjects used to remember to take drugs included (from
      most to least frequently used): making it a routine activity, reading labels, a
      self-devised memory aid, a habit, being reminded by someone else, sorting, and
      noticing symptoms. CONCLUSIONS: Clinicians should provide their patients with
      information about over-the-counter agents as well as prescribed drugs, be alert
      to cues that blacks and men give indicating their need for additional explanation
      about a drug's purposes, and be sensitive to differential prescribing patterns
      with respect to race. When planning a regimen for multiple doses of a drug,
      clinicians should account for their patients' tendencies to use routine
      activities as memory prompts.

PMID- 7633009
TI  - Effects of intravenous famotidine on gastric acid secretion in patients
      undergoing cardiac surgery.
AB  - OBJECTIVE: To determine the effects of cardiopulmonary bypass and famotidine on
      gastric acid secretion in adults undergoing cardiac surgery. DESIGN: Prospective,
      randomized, double-blind, placebo-controlled study. SETTING: University teaching
      hospital. PARTICIPANTS: Eighteen patients undergoing elective cardiac surgery
      with cardiopulmonary bypass. MAIN OUTCOME MEASURES: Famotidine 20 mg or NaCl 0.9%
      placebo was administered intravenously following induction of anesthesia and
      placement of a nasogastric pH probe. A second dose was given 12 hours after
      surgery in the intensive care unit. Gastric pH was measured continuously and
      gastric volume was measured every 4 hours for up to 24 hours after
      cardiopulmonary bypass. RESULTS: Following famotidine administration, pH
      increased by 43% within 45 minutes and remained above 5.5 throughout the study
      period (p < 0.05 vs placebo and baseline). The gastric pH did not increase, but
      remained above 4.0 in most patients in the placebo group for up to 12 hours after
      cardiopulmonary bypass. Gastric volumes were on average 24% lower in the
      famotidine group (p > 0.05). CONCLUSIONS: Gastric acid secretion is decreased
      during and for 12 hours after cardiopulmonary bypass. Perioperative
      administration of famotidine suppresses gastric secretion in cardiac surgery
      patients.

PMID- 7633012
TI  - Knowledge of and attitudes about adverse drug reaction reporting among Rhode
      Island pharmacists.
AB  - OBJECTIVE: To survey pharmacists' knowledge of the adverse drug reaction (ADR)
      reporting process, as well as the nature and seriousness of ADRs observed by
      pharmacists, and to determine how pharmacists perceive their role in monitoring
      and reporting suspected reactions. DESIGN: A survey was mailed to 793 Rhode
      Island pharmacists with a 40% (318) response rate. RESULTS: Two hundred and
      thirty-five surveys were reviewed for final analysis. Pharmacists in retail
      settings were more likely than hospital pharmacists to be aware of ADRs relating
      to therapeutic inequivalence and over-the-counter products, and more likely to
      ask the patient about ADRs (40% vs 16%). Hospital pharmacists were more likely to
      receive ADR information from physicians (40% vs 15%). Almost all pharmacists
      (97%) believed that action should be taken when a serious ADR is suspected.
      Younger pharmacists (< 45 y) were more willing to contact the physician and refer
      the patient to medical attention. CONCLUSIONS: Our results show that fewer than
      half of the respondents (41%) claimed to have observed a serious ADR (potentially
      life-threatening or requiring hospitalization), although almost all (97%)
      believed that pharmacists should take some action when a serious ADR is
      suspected. The influence of the practice setting, the number of years in
      practice, and the number of hours worked per week influenced the reporting
      practices and attitudes.

PMID- 7633013
TI  - Acute pulmonary edema associated with ocular metipranolol use.
AB  - OBJECTIVE: To report a case of pulmonary edema associated with the use of ocular
      metipranolol, a nonselective beta-blocker. CASE SUMMARY: A 72-year-old woman with
      no history of pulmonary or cardiac disease presented to the emergency room with
      signs and symptoms consistent with cardiogenic pulmonary edema. The patient had
      used metipranolol eyedrops approximately 1 hour before becoming symptomatic. When
      rechallenged inadvertently while hospitalized, the patient again became
      symptomatic. The patient's metipranolol eyedrops then were substituted with
      betaxolol eyedrops. She continued to be free of symptoms of pulmonary edema at
      subsequent clinic visits 1, 4, and 6 weeks following discharge. DISCUSSION: This
      is the first reported case of pulmonary edema associated with metipranolol. There
      was a reasonable temporal association between use of the eyedrops and the onset
      of symptoms. Beta-blockers may cause cardiogenic pulmonary edema secondary to
      their negative inotropic and negative chronotropic effects. The drug's lipid
      solubility or a deficiency in the enzyme responsible for its metabolism may have
      allowed the drug to accumulate to a critical concentration over the 6-week period
      of use. CONCLUSIONS: Ocular beta-blockers must be used with caution in patients
      with relative contraindications to beta-blockade. This case illustrates that
      these agents must be used prudently even in patients with no history of
      symptomatic congestive heart failure.

PMID- 7633014
TI  - Cyclosporine and vancomycin disposition during continuous venovenous
      hemodiafiltration.
AB  - OBJECTIVE: To report cyclosporine and vancomycin disposition during continuous
      venovenous hemodiafiltration (CVVHD) in a 41-year-old heart transplant patient
      while in the intensive care unit at a primary and tertiary care teaching
      hospital. CASE SUMMARY: The patient received a 60-mg infusion of cyclosporine
      over 24 hours and vancomycin 1 g over 1 hour. Blood samples subsequently were
      collected and analyzed using whole blood monoclonal radioimmunoassay and
      fluorescence polarization immunoassay, respectively. Blood samples were measured
      every hour from the arterial and venous lines of the apparatus, as were
      ultrafiltrate drug concentrations. Drug clearance rates into the ultrafiltrate
      subsequently were calculated. DISCUSSION: Measurements of ultrafiltrate detected
      no cyclosporine. A slight variation existed between arterial and venous drug
      concentrations, which was not statistically significant (p > 0.05, paired
      Student's t-test). Analysis of vancomycin samples revealed a steady decline of
      drug concentration, with 4.75% of the dose eliminated in the ultrafiltrate.
      Vancomycin arterial and venous concentrations decreased from 24.4 and 23.3 mg/L
      to 15.7 and 12.3 mg/L, respectively. CONCLUSIONS: Vancomycin is eliminated by
      CVVHD and it may be necessary for these patients to receive the drug more
      frequently. In contrast, cyclosporine is not removed effectively by CVVHD;
      therefore, replacement doses are not warranted.

PMID- 7633016
TI  - Sinus arrest after administration of intravenous metoclopramide.
AB  - BACKGROUND: Sinus arrest is a rare complication of metoclopramide administration.
      CASE DESCRIPTION: A 51-year-old woman developed Guillain-Barre syndrome and
      severe dysautonomia. Metoclopramide was administered for the treatment of
      gastroparesis. Sinus arrest followed drug administration on several occasions and
      on rechallenge. CONCLUSIONS: After reviewing the literature and discussing
      possible etiologies for this unusual adverse drug reaction in this setting, we
      recommend that metoclopramide be used with caution in patients prone to develop
      bradyarrythmias, particularly those with dysautonomias and Guillain-Barre
      syndrome.

PMID- 7633015
TI  - Clinafloxacin-theophylline drug interaction.
AB  - OBJECTIVE: To report an apparent pharmacokinetic interaction between
      clinafloxacin and theophylline in a patient with chronic obstructive pulmonary
      disease (COPD). CASE SUMMARY: A patient with a history of COPD was admitted for a
      fracture of the right femoral neck. Admission medications included extended
      release theophylline 400 mg bid. The initial serum theophylline concentration was
      81.03 mumol/L (normal 55-110). A subsequent concentration was subtherapeutic
      (46.62 mumol/L) and the theophylline dosage was increased to 300 mg tid.
      Therapeutic steady-state concentrations were achieved. The patient later
      developed pneumonia and was enrolled in a study of nosocomial acquired pneumonia
      involving clinafloxacin versus ceftazidime. He was randomized to receive
      clinafloxacin 200 mg iv q12h. After clinafloxacin therapy was initiated, the
      serum theophylline concentration increased into the toxic range (155.96 mumol/L).
      Theophylline administration was held for 2 doses and the dosage then reduced to
      200 mg tid. Serum concentrations decreased to within the therapeutic range.
      DISCUSSION: The fluoroquinolones have been shown to interact with the hepatic
      metabolism of theophylline and increase serum theophylline concentrations. The
      quinolone metabolite, 4-oxoquinolone, inhibits the N-demethylation of
      theophylline, leading to a decrease in the clearance of theophylline. The
      resultant rise in theophylline concentrations corresponds with the decrease in
      clearance and possible toxicity. In our patient, careful monitoring of
      theophylline concentrations and dosage adjustments resulted in the restoration of
      therapeutic serum concentrations. CONCLUSIONS: The observation of this drug
      interaction between clinafloxacin and theophylline suggests a need for prudent
      monitoring of theophylline concentrations. Dosage adjustments may be warranted
      when this combination of medications is used. Such action may prevent significant
      toxicities and prolonged hospitalization. Further controlled clinical trials in
      healthy volunteers are needed to substantiate the interaction between
      clinafloxacin and theophylline.

PMID- 7633017
TI  - Multiorgan failure associated with lomustine overdose.
AB  - OBJECTIVE: To report a lomustine overdose in a patient with anaplastic
      astrocytoma. CASE SUMMARY: A 28-year-old woman with anaplastic astrocytoma was
      treated with partial resection and radiation therapy followed by a lomustine
      containing regimen. The patient took lomustine 1400 mg po over a week, her
      regular dose being 200 mg on day 1 of the regimen. Pancytopenia developed within
      a week after the last dose of lomustine and the patient was admitted to the bone
      marrow transplant unit for supportive care. About 3 weeks later, the patient
      gradually developed a multiorgan dysfunction, including liver, brain, and lungs
      without evidence of infection or tumor progression, and died on day 45 of
      hospitalization. DISCUSSION: This is the third reported case of lomustine
      overdose that resulted from supplying the patient with more tablets than needed
      for 1 dose. Although late hematopoietic recovery may be possible after such a
      high dose of lomustine, other organ toxicities might be detrimental. CONCLUSIONS:
      Physicians and pharmacists should avoid supplying more tablets than needed for 1
      lomustine dose. High doses of lomustine may cause irreversible multiorgan
      toxicities.

PMID- 7633018
TI  - Venlafaxine: a structurally unique and novel antidepressant.
AB  - OBJECTIVE: To introduce the new antidepressant venlafaxine. Basic pharmacokinetic
      data and clinical trials are reviewed, as well as adverse reactions, drug
      interactions, dosing guidelines, and therapeutic considerations. The article also
      discusses several pharmacotherapy issues and how venlafaxine compares with other
      available antidepressants. DATA SOURCES: A MEDLINE search was used to identify
      pertinent literature, including reviews. STUDY SELECTION: As this is a relatively
      new agent, all available clinical trials were reviewed. DATA EXTRACTION: All
      clinical trials that were available prior to submission for publication were
      reviewed. Preliminary trials and unpublished reports were not reviewed. DATA
      SYNTHESIS: Venlafaxine hydrochloride is a structurally novel agent that has
      recently been approved in the US for the treatment of depression. This unique
      antidepressant blocks neuronal reuptake of norepinephrine, serotonin, and, to a
      lesser extent, dopamine. Venlafaxine and its major active metabolite, O
      desmethylvenlafaxine, exhibit linear kinetics with an elimination half-life of 5
      and 11 hours, respectively. Venlafaxine has been evaluated in 7 clinical trials
      for the treatment of depression. These have consisted of 2 open trials, 3 double
      blind, placebo-controlled trials, and 2 double-blind trials where venlafaxine was
      compared with trazodone and imipramine. All 7 trials have established efficacy
      for venlafaxine using standard psychiatric rating scales to measure change of
      depressive symptoms. The usual daily dosage ranges from 75 to 225 mg/d in 2 to 3
      divided doses, with a maximum daily dosage of 375 mg/d. The drug's adverse effect
      profile differs somewhat from other more specific serotonin reuptake inhibitors
      in that it appears to cause dry mouth, somnolence, and elevated blood pressure as
      well as nausea, headache, and dizziness. CONCLUSIONS: Although venlafaxine has
      recently become available for use as an antidepressant in the US, few clinical
      trials have been conducted to help the practitioner evaluate its place in the
      treatment of depression. There are no comparative trials of venlafaxine with the
      serotonin specific reuptake inhibitor antidepressants, which are rapidly becoming
      the newest comparative standard. The clinical place for venlafaxine in the
      treatment of depression has yet to be determined.

PMID- 7633019
TI  - Torsemide: a pyridine-sulfonylurea loop diuretic.
AB  - OBJECTIVE: To review the clinical pharmacology of torsemide and to compare it
      with currently available loop diuretics, particularly furosemide. DATA SOURCES:
      An English-language MEDLINE search, 1985 to October 1994, was used to identify
      pertinent literature, including review articles. DATA EXTRACTION: Data from
      scientific literature were extracted, evaluated, and summarized for presentation.
      Pivotal and representative studies are discussed relating to the pharmacology,
      pharmacokinetics, and use of torsemide in patients with congestive heart failure,
      renal disease, hepatic disease, and hypertension. DATA SYNTHESIS: Torsemide is a
      loop diuretic of the pyridine-sulfonylurea class. The bioavailability of
      torsemide is approximately 80%, with little first-pass metabolism, and torsemide
      can be given without regard to meals. The serum concentration reaches its peak
      within 1 hour after oral administration and diuresis lasts approximately 6-8
      hours. Torsemide is eliminated both hepatically (80%) and renally (20%) as
      unchanged drug with an elimination half-life of about 3.5 hours. Because of the
      high bioavailability, oral and intravenous doses are therapeutically equivalent.
      Torsemide, and other loop diuretics such as furosemide, are indicated for the
      treatment of edema associated with congestive heart failure, renal disease, and
      hepatic disease. They also are indicated for the treatment of hypertension alone
      or in combination with other antihypertensive agents. Depending on the
      indication, the recommended initial adult dosage of torsemide is between 5 and 20
      mg once daily orally or intravenously. Special dosage adjustments in the elderly
      are not necessary. CONCLUSIONS: Torsemide is a loop diuretic similar to
      furosemide, with similar indications. Torsemide is characterized by good
      bioavailability and once-daily dosing and, compared with furosemide, provides
      generally equivalent therapeutic efficacy.

PMID- 7633020
TI  - Bisoprolol: is this just another beta-blocker for hypertension or angina?
AB  - OBJECTIVE: To review the pharmacology, pharmacokinetics, and clinical experience
      with bisoprolol and make recommendations regarding its potential clinical
      usefulness, as well as considerations for formulary inclusion. DATA SOURCES:
      Reference citations were sought from Index Medicus and Science Citation Index.
      Data were collected from abstracts and articles describing experimental studies
      or blind clinical trials. STUDY SELECTION: Studies designed in a randomized,
      blind, and placebo-controlled manner were emphasized. Studies also were included
      if bisoprolol was evaluated comparatively with other agents in a randomized,
      blind fashion. DATA EXTRACTION: Data from human studies published in English were
      evaluated. Studies were assessed by sample size and the clarity of descriptions
      of methods and results. DATA SYNTHESIS: Bisoprolol reduces systolic and diastolic
      blood pressures in patients with hypertension for a 24-hour dosing interval and
      is associated with beneficial hemodynamic effects in patients with myocardial
      ischemia. It is devoid of intrinsic sympathomimetic activity and membrane
      stabilizing effects at therapeutic dosages. In patients with hypertension,
      bisoprolol diminishes plasma renin activity, platelet aggregation, effective
      renal plasma flow, and creatinine clearance. Bisoprolol has minimal effects on
      glucose tolerance and plasma lipid profiles. Monotherapy with bisoprolol is as
      effective as with atenolol, nitrendipine, or nifedipine. Low-dose combination
      therapy with hydrochlorothiazide is at least as effective as either bisoprolol or
      hydrochlorothiazide alone. Preliminary experience in the management of angina
      pectoris suggests that bisoprolol is at least as efficacious as atenolol or
      verapamil. Thus far, reported adverse effects are similar to those of other beta
      blockers. No clinically important drug interactions have been reported at this
      time.

PMID- 7633021
TI  - Beta-lactam antibiotics: is continuous infusion the preferred method of
      administration?
AB  - OBJECTIVE: To examine the pharmacodynamic properties of the beta-lactam class of
      antibiotics and the rationale for their continuous infusion (CI), and to explore
      reasons that this mode of administration has not replaced intermittent infusion
      as the standard of practice. DATA SOURCES: A Medline search of the English
      language literature evaluating CI administration of beta-lactam antibiotics was
      conducted. Bibliographic searches of these articles also were performed. STUDY
      SELECTION: Because there were few human trials, all available trials were
      considered for review. A cross section of clinical trials, animal studies, and in
      vitro studies examining the impact of the route of antibiotic administration was
      selected for each pharmacodynamic variable addressed. DATA SYNTHESIS: The support
      for CI as the preferred method of beta-lactam administration comes primarily from
      in vitro and animal data. Most beta-lactam antibiotics do not demonstrate
      concentration-dependent killing and have an appreciable postantibiotic effect
      only against gram-positive cocci. Their efficacy appears to be optimized by
      maintaining suprainhibitory concentrations throughout the dosing interval.
      Therefore, CI of beta-lactams could potentially enhance the efficacy of treatment
      or allow less drug to be used on a daily basis. This has yet to be demonstrated
      convincingly in human clinical trials. Comparative trials need to continue to
      explore the impact of the method of administration on patient outcomes such as
      duration and cost of therapy, as well as morbidity and mortality. CONCLUSIONS:
      Results of many animal and in vitro studies suggest that CI may be the optimal
      method of beta-lactam administration. Clinical trials need to further document
      the impact of the method of beta-lactam administration on the incidence of
      adverse effects, emergence of bacterial resistance, and patient outcome.
      Pharmacodynamic studies defining target beta-lactam concentrations, the
      practicality of CI in patients requiring multiple intravenous fluids and
      medications, and the pertinence of this issue when beta-lactam antibiotics are
      used as sole agents or in combination with other antimicrobials require further
      exploration.

PMID- 7633022
TI  - Xanthine interference with dipyridamole-thallium-201 myocardial imaging.
AB  - Both theophylline and caffeine have been shown to antagonize adenosine and are
      associated with false-negative test results with dipyridamole-T1-201 imaging.
      This has led to recommendations for theophylline and caffeine abstinence for at
      least 24 hours prior to dipyridamole-T1-201 imaging. Because pentoxifylline and
      its metabolites are structurally similar to theophylline and caffeine, and
      pentoxifylline has adenosine antagonistic properties, one might presume that
      pentoxifylline may also attenuate the diagnostic yield of dipyridamole-T1-201
      imaging. To the best of our knowledge, the pharmacodynamic interaction between
      pentoxifylline and dipyridamole and its effects on dipyridamole-T1-201 imaging in
      patients have never been studied adequately. However, a single study in 7 dogs
      does suggest that there may be no significant interaction. In addition, we must
      also consider the nonacute nature of the clinical use of pentoxifylline in
      peripheral vascular disease and the critical need for accurate dipyridamole-T1
      201 imaging results and the cost associated with this procedure. Until such
      information is available in humans, it would be prudent to discontinue
      pentoxifylline, in addition to caffeinated foods, caffeine-containing drug
      products, and theophylline, at least 24 hours prior to dipyridamole-T1-201
      imaging.

PMID- 7633023
TI  - Hyperkalemia and high-dose trimethoprim/sulfamethoxazole.
AB  - Evidence from the literature strongly supports that high doses of TMP, as used in
      the treatment of PCP in AIDS patients, have the propensity to cause hyperkalemia
      by inhibiting sodium channels in the distal nephron, thereby impairing potassium
      secretion. The mechanism of TMP-induced hyperkalemia is believed to be similar to
      that of triamterene and amiloride because of the structural similarity of these
      agents. It is also possible that declining renal function, which is a natural
      progression of HIV disease, may contribute to the hyperkalemia seen in this
      patient population. In addition, patients with AIDS also may exhibit a defect in
      adrenal function, potentiating the hyperkalemic effect of TMP therapy. Therefore,
      it is crucial for clinicians to monitor closely the serum potassium concentration
      in this patient population, especially during therapy with high doses of TMP.

PMID- 7633024
TI  - Felbamate-induced delayed anaphylaxis.

PMID- 7633025
TI  - Optimal gentamicin dosing in neonates.

PMID- 7633026
TI  - Angioedema caused by ramipril.

PMID- 7633027
TI  - Flaws in multicenter, placebo-controlled studies with anxiolytics in Japan.

PMID- 7633028
TI  - Beneficial effects of low-dose dopamine in cirrhosis and renal insufficiency.

PMID- 7633029
TI  - Changes in the staffing mix in operating departments.

PMID- 7633030
TI  - Scaling the patient's temperature--Part 2.

PMID- 7633032
TI  - Surgery under siege.
AB  - In September of last year I accompanied a team of orthopaedic surgeons to
      Sarajevo in Bosnia. This followed an appeal from the doctors there, and was made
      through World Orthopaedic Concern. The purpose of our visit was two-fold. Firstly
      to write a detailed medical report highlighting the needs of the hospitals, and
      secondly to give support to the surgical and nursing staff.

PMID- 7633031
TI  - Angioscopy in femoral popliteal bypass graft.
AB  - Angioscopy is part of a new armoury of minimally invasive 'keyhole' surgery. Like
      other 'scopes' it enables the surgeon to have a direct view of the interior of
      the body with greatly reduced surgical intervention. An angioscope is an ultra
      thin multi-bundle fibre scope which has manual flexibility. Its tiny diameter
      (1.4mm at smallest) enables the scope to be introduced into the distal vessels of
      the lower leg. As with other scopes the view is seen on a video screen monitor.
      So, angioscopy enables surgeons to access the interior of body vessels for the
      first time, providing vital information on vessel condition during operative
      procedures.

PMID- 7633033
TI  - Reflections--scope for improvement.

PMID- 7633034
TI  - Law workshop for theatre nurses.

PMID- 7633035
TI  - Minimally invasive surgery.

PMID- 7633036
TI  - Is this the way forward?

PMID- 7633038
TI  - Professional and managerial issues in day surgery.

PMID- 7633037
TI  - No more babies--a patient's eye view.

PMID- 7633039
TI  - Men behind the instruments (1). Volkmann, Richard Von (1830-1889).

PMID- 7633040
TI  - Working together.

PMID- 7633041
TI  - Operating from a distance--new directions in perioperative nursing education.
AB  - Australia is home to only 17 million people, most of whom live in the coastal
      areas around the State capital cities. But there are numerous smaller cities,
      towns and communities scattered in the inland rural areas. Communicating between
      these centres has proved to be quite a challenge since early settlers arrived and
      remains so today. Providing education to the population who live away from the
      capital cities and university centres continues to be a challenge. Many
      universities, in an attempt to overcome the distance factor, offer external
      studies courses--the old correspondence courses. Providing a specialty nursing
      course via external studies had never been attempted in Australia until the NSW
      College of Nursing took the plunge in 1990 and pioneered a certificate course in
      perioperative nursing. We were encouraged by the success of a similar venture in
      Canada some years before.

PMID- 7633042
TI  - A third career.

PMID- 7633043
TI  - Is day surgery for you?

PMID- 7633044
TI  - Day surgery in Wales.

PMID- 7633045
TI  - The concept of advocacy.
AB  - In safeguarding the patient, the nurse supports and thereby advocates the
      patient's interests in teh restoration of the patient's health and well-being.
      This article explores the concept of advocacy, discusses some of its complex
      issues and highlights its implications for nursing practice with some reference
      to the theatre setting. An advocate is one who pleads the cause of another.
      According to Tschudin, advocacy is a fundamental aspect of an ethic of caring in
      that with courage born of compassion one is able to respond in a caring way to
      the needs and rights of another. An advocate must take positive steps to restore
      another person's autonomy when it is threatened or diminished, otherwise all talk
      of advocacy is simply lip-service. In theatre nursing the scope for acting as the
      patient's advocate is a reality because most surgery necessitates the use of
      general anaesthesia resulting in the patients' loss of consciousness and they are
      therefore unable to maintain their own interests. The anaesthetised patient who
      has entrusted his life into the hands of the theatre team relies on this duty of
      care to maintain his dignity and safety. As Bandman and Bandman purport, the
      nurse recognises that his or her first duty is to protect and care for the
      patient's health and safety.

PMID- 7633046
TI  - Preoperative patient fasting regimes.
AB  - Twenty years ago, Hamilton Smith undertook an extensive research study into the
      practice of patient fasting times. Data was collected by interviewing nurses and
      anaesthetists in four hospitals, to ascertain whether individual regimes were
      planned for patients. The large study looked at a wide range of issues and it was
      found that 'blanket' fasting was the general practice. Hamilton Smith discovered
      that, despite research showing that safe fasting times ranged from four to six
      hours, patients' prepared for surgery in the morning were all fasted from
      midnight. This sometimes resulted in a starvation period of up to twelve hours.
      Fasting patients irrespective of individualised time of surgery, does not reflect
      individual care.

PMID- 7633047
TI  - Meniscal suturing.
AB  - There is a popular misconception that the meniscus is avascular and that tears of
      the meniscus do not heal. Over the years this notion has gradually been dispelled
      as being incorrect and the fact that the periphery of the meniscus is in fact
      vascular has been accepted. Attempts to resuture this particular structure in the
      knee have, in some cases, proved to be very successful.

PMID- 7633049
TI  - Fears for the future.

PMID- 7633048
TI  - Man behind the instrument (2). Halstead, William Stewart (1852-1922).

PMID- 7633050
TI  - Accountability--its implications for theatre nurses.
AB  - The United Kingdom Central Council for Nursing, Midwifery and Health Visiting
      (UKCC), in its revised Code of Professional Conduct (June 1992) states that, 'As
      a registered nurse ... you are personally accountable for your practice', and
      goes on to identify sixteen clauses which define how we are now obliged to
      exercise that accountability. The inclusion of the word 'personally' in the
      revised text places the responsibility for professional development and standards
      of care firmly in the hands of the individual practitioner. The aim of this paper
      is to explore the relevance of professional accountability to the nurse
      practitioner in the operating department, and how the care she gives, the skills
      she uses and her relationships with other members of the theatre team, are
      affected by its implications.

PMID- 7633051
TI  - 'Nursing should become a research-based profession'--has it?
AB  - I decided to write this article to promote discussion among my colleagues after
      my experience of doing clinical research of my own. I did a small clinical trial
      on the use of Sea-Bands (wrist sweat bands) to put pressure on an acupuncture
      site to relieve postoperative nausea. This has been published in the Nursing
      Times. I am a theatre sister and have a reasonably academic background having
      obtained both an Open University BA and a teaching certificate plus a number of
      nursing courses. Therefore, I had good access to staff and patients and enough
      confidence to embark on the project. However, I had no experience in research
      work, and perhaps it is not surprising to find that there is no back-up within
      'the system' to sustain this type of work. I went to everyone that I could think
      of for help and advice to formulate my data collection protocol. I gleaned small
      nuggets of advice from the local college of nursing, from the community research
      liaison doctor, and from the ethical committee chairman but it was a long hard
      slog which would have deterred me from starting had I realised at the outset how
      many hours of my own time it would take me.

PMID- 7633052
TI  - Healthcare and the environment.
AB  - There are many reasons why you should be concerned about the environment,
      particularly if you are a healthcare professional. Every environmental pollutant
      is also associated with a human health risk. So improving the environment will
      mean better healthcare. In addition we should make sure all our actions are such
      as not to impair the development of future generations. National governments and,
      in particular, the European Commission have recognised this public concern and
      have generated a large amount of environmental legislation in order to change the
      way we behave. A summary of this legislation is provided along with more detailed
      discussions on waste legislation.

PMID- 7633053
TI  - Star performer?

PMID- 7633054
TI  - African Diary. Mozambique maternity matters.

PMID- 7633055
TI  - PREP. Further insights.
AB  - Now that the UKCC has made final decisions about the implementation of the
      proposals for post registration education and practice, it is perhaps time to
      take a long look at what has been happening in the nursing profession during the
      ten years since the first Project 2000 paper was published.

PMID- 7633056
TI  - Man behind the instrument (3). Lane, William Arbuthnot (1856-1943).

PMID- 7633057
TI  - NHS plastic surgery--is it what you think it is?
AB  - Many people who do not come into contact with plastic surgery in their hospitals
      may be under the popular misconception that plastic surgeons spend their time
      fixing noses and altering the size of breasts. Well, yes they do, but only
      occasionally in the NHS: they are more likely to do this type of surgery in their
      private practice. I would like to try to alter perceptions of plastic surgery,
      partly because I am Sister in Charge of a busy Regional Plastic, Burns and
      Reconstructive Theatre Unit and, partly, because I firmly believe that the
      psychology of the small number of patients who do have rhinoplasties and breast
      or cosmetic surgery in the NHS needs to be accepted and understood by busy health
      care workers. I hope to show that cosmetic or aesthetic surgery is a very small
      part of what happens in plastic surgery today. To do this I have used Plastic
      Surgery in the British Isles, a plan for the rest of the 1990s and my own
      hospital consultant episodes for the year 1992/93 as my background information.

PMID- 7633059
TI  - Changes in practice result in deterioration in patient care and undue pressure on
      staff.

PMID- 7633058
TI  - Rediscovering theatre nursing.
AB  - I must begin by saying that I am not a theatre nurse. My professional background
      is very much in medical nursing and I did not begin to think about theatres until
      I became a nurse teacher. It was then I found myself helping to prepare nurses
      for their alloction to theatres and, later, listening to their accounts of their
      experiences. I have to say that theatres were not, and are still not, a highspot
      in pre-registration courses as far as the majority of students are concerned. As
      a tutor, particularly as I became more involved in the development of Project
      2000, I began to ask myself why this was. What were the implications and did
      theatre experience really matter. During the last year I have been talking to
      theatre nurses in different hospitals about how they see their work and whether
      tutors should still be sending them students. These talks have been very informal
      but my objective was to tease out the nursing element of theatre work. I very
      much support the view that theatre nursing exists and that it can be made
      explicit. I must emphasise at this stage that this work is very much in its
      infancy and, as yet, lacks strong theoretical dimensions. Comments and
      contributions from readers will be very welcome.

PMID- 7633060
TI  - What cost ritual?
AB  - Following the 1991 Nuffield Theatre Nurses Award, I was encouraged to pursue
      further research into the scrub procedure. My interest had originally started
      when looking at the possibility of installing electronic eye taps into the
      theatres. I reasoned that by reducing the amounts of heated water flowing unused
      during the scrub procedure I would be able to justify the cost of these taps. A
      pilot survey I undertook showed that on costs alone this was not proven. A more
      logical and research based approach to the subject was required. My main
      objectives were to ascertain costs and timings of the traditional scrub; compare
      the costs with other acceptable alternatives; explore 'costs' relating to wider
      environmental concerns; examine the effectiveness of current practice. I looked
      at the Government statistics for England during 1990/91. It showed an annual
      total of 741,393 operating sessions with a total of 3,353,797 operations
      performed. The total of cases in orthopaedic, opthalmic, general and
      gynaecological operations totalled 2,301,272 cases. These four categories were
      the ones I chose to research.

PMID- 7633061
TI  - Preceptorship.
AB  - The Health Service, nursing and education have witnessed some wide-ranging
      changes over the last few years. Education and 'keeping up to date' is playing an
      ever increasing role within nursing. There is no exception within theatres. Over
      the last 10 years we have seen the introduction of 'Project 2000' meaning fewer
      nurses coming to theatres after they have qualified and more recently we have
      seen the government introduce the National Vocational Qualification. We have also
      heard numerous terms such as role model, mentors, facilitators, assessors,
      supervisors and more recently the term preceptor and preceptorship.

PMID- 7633063
TI  - Writing for publication.
AB  - Getting published can be a very rewarding experience. Seeing your work in print
      with the knowledge that many colleagues and other health care professionals are
      reading it can do your self-esteem no end of good. Having your work published
      also enables you to communicate information to an audience that you otherwise
      would not reach.

PMID- 7633062
TI  - The patient's charter--its implications for surgery.
AB  - In recent years charters have become fashionable; we now have charters issued by
      the Water Board, London Electricity, British Rail, a Patient's Charter from April
      '94, a Childbirth Charter, and many more. They all promise to give a better all
      round quality of service to the public and the Patient's Charter is no exception.
      This document is a central part of the government's programme to improve and
      modernise the delivery of the NHS service to the public while continuing to
      reaffirm the fundamental principles of the NHS. Aneurin Bevan's dream of free
      health care for all citizens of this country became a reality in 1948 and, for
      over 30 years, it was the envy of the world. Patients had good reason to be
      grateful for the speed with which they were admitted to hospital and the high
      standard of care they received.

PMID- 7633064
TI  - Man behind the instrument. Moynihan, Berkeley George Andrew (1865-1936).

PMID- 7633065
TI  - The perioperative care of the paediatric neurosurgical patient.
AB  - The Queen's Medical Centre, University of Nottingham, is one of the largest neuro
      science centres in Britain and serves a population of five million people. Its
      catchment area covers the counties of Nottinghamshire, Leicestershire, Derbyshire
      and Lincolnshire though patients are often referred from other parts of Britain
      and from abroad. The total number of neuro-paediatric beds is 20 plus access to
      12 beds in the paediatric intensive care unit and 18 beds of the neonatal unit.
      In the year 1992 the total number of operations was 300, a number which increased
      by 25% the following year and included such operations as craniostenosis,
      craniotomies, spinal surgery, repair of meningocele, shunts, implanting and
      endoscopic and stereotactic procedures.

PMID- 7633066
TI  - Foreveroscopy. How to survive laparoscopic surgery.

PMID- 7633067
TI  - Theatre nursing (Part 1).
AB  - Whilst discussing the need to increase the number of theatre nurses, Professor
      Roger Dyson claimed that nurses overtly tended to devalue theatre work as not
      being 'real nursing'. Many nurses who work outside theatre may support this.
      Sadly, this may be further supported by theatre nurses themselves. Such
      statements as 'I know I'm a good nurse because I can scrub for anything' is a
      comment which has been made to this author on more than one occasion. As Casey
      states, the conventional image of nurses in theatre is less about nursing and
      more about technical assistance with operating procedures.

PMID- 7633068
TI  - Theatre nursing in the video age.

PMID- 7633069
TI  - Models, marketing and market forces.

PMID- 7633070
TI  - African diary.

PMID- 7633071
TI  - Twenty years on.

PMID- 7633072
TI  - Right person: right time: right place. A report on the NATN manpower planning
      workshop, Keele University, July 1994.

PMID- 7633073
TI  - Just a glove?
AB  - Surgical gloves were introduced in the early years of this century, initially to
      protect nurses' and surgeons' hands from the strong antiseptic chemicals used
      during surgery. William Stewart Halstead is generally credited with introducing
      gloves to protect his scrub nurse (who later became his wife) from the carbolic
      acid in which the instruments were immersed. They soon became an essential
      requirement for asepsis and today, along with procedure gloves, are seen to
      protect both staff and patients from blood borne infections such as Hepatitis B
      and HIV. But, how many of us question the dangers posed to patients and staff
      through gloves? Most of us have read about the dangers of starch, but gloves may
      pose other significant risks to all who come into contact with them. 'With an
      ever increasing number of workers who don gloves as a means of personal
      protection, increased incidents of dermatitis, anaphylactic reactions, and
      respiratory problems from airborne antigens from glove powders have raised new
      concerns about allergies.'

PMID- 7633074
TI  - The importance of risk management.

PMID- 7633075
TI  - EORNA meeting. Stockholm--May 1994.

PMID- 7633076
TI  - The 4th World Congress for Nurse Anaesthetists. Paris, May 12-15 1994.

PMID- 7633077
TI  - The complacent operator.

PMID- 7633078
TI  - Ball and socket inc. Orthopaedics as a business.

PMID- 7633079
TI  - On the receiving end.
AB  - Four years ago I was a tired and angry parent when I put pen to paper to record
      my experiences which are now printed in the ensuing article. Today I can look
      back without being so influenced by the protective instincts of parenthood and
      communicate objectively to all nurses who work in the paediatric field.

PMID- 7633080
TI  - Supping with the devil.

PMID- 7633081
TI  - Sarajevo UK Med Tour 1994.
AB  - At the beginning of July a team of seven left the UK to go to Sarajevo to help in
      the reconstruction of plastic surgical services in the city. The team consisted
      of one plastic surgeon, two SR anaesthetists, a scrub nurse, Lesley Fudge, and
      anaesthetic nurse, Dina Plowers, a ward sister and a hand therapist.

PMID- 7633083
TI  - An interview with Professor Bevan. Interview by Ann-Carol Carrington.

PMID- 7633082
TI  - An interview with Baroness Cox.

PMID- 7633084
TI  - Perspectives on clinical negligence in the operating theatre.
AB  - John Tingle looks at clinical negligence in his continuing analysis of how the
      law affects nurses and other clinical staff in the operating theatre. Everybody
      makes mistakes or errors at sometime or other in their careers. Some mistakes
      will not cause any injury and will be easily corrected whilst others may go
      unnoticed and may never be picked up by the patient or healthcarer. In recent
      years, however, patients do seem increasingly prepared to complain and in some
      cases to take legal action for compensation when their healthcarers' mistakes
      have caused them injury. It is important to stress that not every mistake can be
      categorised as negligence. A number of principles of negligence law have to be
      applied and satisfied before such a claim can be made.

PMID- 7633086
TI  - Damp dusting in the operating theatre: implications for bacteria counts.
AB  - This paper describes a research study replicating and expanding on Pickering's
      paper on damp dusting and its effect on bacteria counts, which concluded that
      there had been little difference in the counts for both the damp dusting and non
      damp dusting period. However there were unexplained fluctuations in levels of
      bacteria that the author could not explain. A recommendation of the study was to
      try to ascertain whether damp dusting alters airborne concentrations or whether
      it is a combination of other variables. This study hoped to explain this.

PMID- 7633085
TI  - Prevention of hypothermia during anaesthesia.
AB  - A study of the hypothermic effects of general anaesthesia during breast surgery
      and its amelioration by the use of a thermal drape to most of the body exclusive
      of the operating site. Two groups of patients are compared, using a constant
      anaesthetic technique, a single surgeon and the same operating conditions except
      for the omission or inclusion of thermal drapes. A review of the homeostatic
      mechanisms of temperature control and other methods of maintaining body
      temperature are included.

PMID- 7633087
TI  - Ignorance is not bliss. Informed consent.

PMID- 7633088
TI  - African diary: our first visit to the bush.
AB  - We have, at last, received further despatches from Diana Rigby. She has been at
      her mission station in Mozambique, now, for some three years. Those of you who
      have followed her diary notes will have realised that these three years have not
      been uneventful. Following her knee surgery Diana is now back in the bush putting
      a fair amount of stress on that knee, by the sound of it. The civil war is over
      in Mozambique and these letters give some idea of the immense amount of work
      needed to pull together a country which has suffered in this way.

PMID- 7633089
TI  - Man behind the instrument (9). McIndoe, Archibald Hector (1900-1960).

PMID- 7633090
TI  - Caring for health and safety counts.

PMID- 7633091
TI  - The nurse as surgeons assistant.

PMID- 7633092
TI  - Anaesthesia for neurosurgery--essentials of anaesthesia.
AB  - Paul Rooney continues his series of articles on anaesthetics. In approaching the
      topic of anaesthesia for neurosurgery he is aware of the need for a clear
      understanding of basic anatomy and physiology of the central nervous system.

PMID- 7633093
TI  - Safe practices in neurosurgery?
AB  - Having worked in and visited a number of neurosurgical theatres, I was surprised
      at how greatly the practice of accounting for swabs, patties and other such items
      differs from one hospital to another. I intended to revise the swab policy within
      my own theatre, and felt that it was necessary to establish what safety measures
      were being taken in other neurosurgical theatres throughout the country. This
      small study was not intended as a formal piece of research but to assist in
      identifying safe practices common to neurosurgical theatres. The results show
      that practices in many neurosurgical theatres are varied, and fall short of the
      safeguards laid down by our nursing and medical professional bodies. This is
      particularly worrying when claims involving retained swabs and instruments are
      brought more often than for any other surgical damage. Guidelines and
      recommendations for safe practices in the operating room have been widely
      accepted for decades and are often referred to in a court of law when a case for
      damages is brought. This small study looks at the practice of accounting for
      swabs, needles and other 'countable' items in neurosurgical theatres throughout
      England, Scotland and Wales.

PMID- 7633095
TI  - African diary.

PMID- 7633094
TI  - Duty of care--(1).
AB  - This series of articles seeks to examine three issues of current importance to
      nurses: Firstly the duty of care which nurses are legally bound to observe.
      Secondly the ways in which nurses may enhance their confidence in their ability
      to advocate on behalf of their patients/clients, thus attaining competence.
      Thirdly, the effects upon individuals who do speak out in obedience to the code
      of practice as laid down by the United Kingdom Central Council for Nurses, Health
      Visitors, and Midwives. The articles are adapted from a lecture given by the
      writer at the annual NATN conference in Harrogate in October 1994, entitled "Are
      Nurses the Patients' Advocates?".

PMID- 7633096
TI  - Theatre nurses' political agenda for the future.

PMID- 7633097
TI  - Change: the OR challenge.

PMID- 7633098
TI  - Nursing management of the patient undergoing stereotactic surgery.

PMID- 7633099
TI  - Clinical reviews: the denouement of investigations in medicine.

PMID- 7633100
TI  - Endometriosis: appearance and detection with conventional and contrast-enhanced
      fat-suppressed spin-echo techniques.
AB  - Suspected pelvic endometriosis was prospectively evaluated in 31 women with T1-
      and T2-weighted conventional spin-echo (CSE) magnetic resonance imaging alone and
      in combination with T1-weighted fat-suppressed (T1FS) and gadolinium-enhanced
      T1FS (Gd-T1FS) spin-echo techniques. Images were grouped for interpretation and
      comparison as follows: (a) CSE alone, (b) CSE/T1FS, and (c) CSE/T1FS/Gd-T1FS. All
      patients underwent surgery within 3 months of imaging, and 21 patients were found
      to have endometriosis: 59 endometriomas (26 large and 33 small) and 51 sites of
      implants were seen. With CSE images, 23 large and six small endometriomas were
      detected. With CSE/T1FS images, 25 large and 14 small endometriomas were
      identified. With CSE/T1FS/Gd-T1FS images, 24 large and 14 small endometriomas
      were detected and ill-defined areas of enhancement were noted in 22 sites
      throughout the pelvis. These corresponded to endometriotic implants seen at
      surgery in 14 sites. The sensitivity, specificity, and accuracy, respectively,
      for the detection of endometriosis were 76%, 60%, and 71% for CSE, 86%, 50%, and
      74% for CSE/T1FS, and 81%, 50%, and 71% for CSE/T1FS/Gd-T1FS images. No
      significant differences (P > .1) between image combinations for correctly
      identifying patients with and without endometriosis were seen. The difference in
      sensitivity between CSE and CSE/T1FS and between CSE and CSE/T1FS/Gd-T1FS images
      for detecting small endometriomas was significant (P = .03).

PMID- 7633101
TI  - MR monitoring of focused ultrasonic surgery of renal cortex: experimental and
      simulation studies.
AB  - The aim of the study was to test the hypothesis that magnetic resonance (MR)
      imaging-guided and -monitored noninvasive ultrasonic surgery can be performed in
      highly perfused tissues from outside the body. A simulation study was performed
      to evaluate the optimal sonication parameters. An MR-compatible positioning
      device was then used to manipulate a focused ultrasound transducer in an MR
      imager, which was used to sonicate kidneys of five rabbits at various power
      levels and different durations. Temperature elevation during sonication was
      monitored with a T1-weighted spoiled gradient-echo sequence. The simulation study
      demonstrated that a sharply focused transducer and relatively short sonication
      times (30 seconds or less) are necessary to prevent damage to the overlying skin
      and muscle tissue, which have a much lower blood perfusion rate than kidney. The
      experiments showed that the imaging sequence was sensitive enough to show
      temperature elevation during sonication, thereby indicating the location of the
      beam focus. Histologic evaluations showed that kidney necrosis could be
      consistently induced without damage to overlying skin and muscle. The study
      demonstrated that highly perfused tissues such as the renal cortex can be
      coagulated from outside the body with focused ultrasound and that MR imaging can
      be used to guide and monitor this surgery.

PMID- 7633102
TI  - Pancreatic signal intensity on T1-weighted fat saturation MR images: clinical
      correlation.
AB  - To determine whether signal intensity (SI) of the pancreas that was less than
      that of liver on T1-weighted fat-suppressed (T1FS) magnetic resonance (MR) images
      could be used to help predict the presence of pancreatic disease, three blinded
      independent observers graded pancreatic SI relative to liver and/or renal cortex
      in 89 patients on T1FS images. Results were correlated with patient age and
      diagnosis. Among the 47 patients with a clinically normal pancreas, pancreatic SI
      was higher than that of liver in 42 and equal to that of liver in the rest, none
      of whom had evidence of fatty pancreas. These five patients had a mean age of 71
      years, compared with 55 years for patients whose pancreas was more intense than
      liver (P = .02). Of the 42 patients with a clinically abnormal pancreas, only
      eight had pancreatic SI higher than that of liver. The positive predictive value
      for normal pancreas of an SI higher than that of liver was 84% and the positive
      predictive value for abnormal pancreas of an SI less than or equal to that of
      liver was 88%, with an overall accuracy of 86%. If normal pancreatic SI is
      defined as higher than that of liver for patients younger than 60 years and as
      equal to or higher than that of liver for patients older than 60 years, the
      positive predictive value of normal SI becomes 76%, the positive predictive value
      of decreased SI becomes 100%, and the overall accuracy becomes 83%.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7633103
TI  - Hepatic tumors: magnetization transfer MR imaging with gadolinium enhancement.
AB  - Thirty patients with 15 hepatocellular carcinomas, 10 metastases, four
      hemangiomas, and one cholangiocarcinoma underwent magnetic resonance imaging at
      1.5 T with T1-weighted, T2-weighted spin-echo (SE) images, gradient-echo (GRE)
      magnetization transfer (MT) images, and gadolinium-enhanced T1-weighted SE and MT
      GRE images. The MT effect and lesion-liver contrast-to-noise ratio (C/N) were
      calculated and visual assessment (qualitative analysis) performed for unenhanced
      and enhanced MT-GRE images and enhanced T1-weighted SE images. The C/N values for
      hepatic adenocarcinomas (seven metastases and one cholangiocarcinoma) and
      hemangiomas were larger for enhanced MT-GRE images (adenocarcinoma, 8.4 +/- 2.3
      [P < .01]; hemangioma 24 +/- 2.1 [P < .05]) than for enhanced GRE images (5.0 +/-
      1.9 and 18 +/- 2.7, respectively). These enhancing tumors had the highest scores
      in the qualitative analysis. Enhanced MT-GRE images showed no advantage for
      depiction of hepatocellular carcinomas relative to the other images.

PMID- 7633104
TI  - Proton MR spectroscopy in quantitative in vivo determination of fat content in
      human liver steatosis.
AB  - To demonstrate that the lipid volume fraction in liver steatosis can be
      accurately estimated with in vivo hydrogen-1 magnetic resonance (MR)
      spectroscopy, the authors developed a calibration procedure based on in vitro MR
      spectroscopy of lipid extracts from steatotic liver specimens. The lipid volume
      fractions determined with the calibration procedure were compared with the
      results of histomorphometry and with calibrated computed tomographic (CT) data.
      The volume fraction of fat determined with MR spectroscopy was in good agreement
      with the CT results, whereas histomorphometry underestimated the amount of
      hepatic fat. The results indicate that determination of the fat volume fraction
      in steatotic liver can be achieved noninvasively with MR spectroscopy.

PMID- 7633105
TI  - MR imaging of myositis ossificans: variable patterns at different stages.
AB  - Five patients with a palpable mass at presentation underwent magnetic resonance
      (MR) imaging. The final diagnosis was myositis ossificans (MO). MR imaging
      features, particularly after injection of gadopentetate dimeglumine, mimicked
      those of an inflammatory mass or neoplasm. The lesions were excised in three
      patients, and the images were correlated with histologic findings. Three
      different appearances were noted on MR images, corresponding to the stages of
      maturation of MO. Two cases involved early-stage lesions, and T1-weighted MR
      images showed a mass with homogeneous intermediate signal intensity. Both lesions
      showed rim enhancement after contrast agent injection and high signal intensity
      on T2-weighted images. Pathologic specimens demonstrated stroma with masses of
      spindle cells in which osteoid production was interspersed. The enhanced rim of
      the lesion mimicked the expected MR appearance of an abscess or necrotic tumor.
      Areas of enhancement in adjacent muscle were also seen on postcontrast T1
      weighted images. Intermediate-stage MO was present in one case; there was
      evidence of a thin rim of calcification on plain radiographs and fatty changes in
      the lesion on T1-weighted images, corresponding with histologic findings. One
      case of a mature lesion showed a considerable degree of peripheral calcification
      both on MR images and at histology. MR imaging is nonspecific in the diagnosis of
      early-stage MO.

PMID- 7633106
TI  - Fast spin-echo imaging of the temporomandibular joint.
AB  - The applicability of a fast spin-echo (FSE) technique for magnetic resonance
      imaging of the temporomandibular joint (TMJ) was studied, and the technique
      compared with a conventional spin-echo (CSE) technique. Sagittal T1-weighted CSE
      and dual-echo FSE images of 50 TMJs in 25 patients with symptoms of internal TMJ
      derangement were compared. CSE and FSE images were diagnostically comparable in
      22 TMJs (44%). The FSE technique was rated better than CSE imaging for
      delineation of the disk in 26 joints (52%), whereas the CSE technique was rated
      better in only two joints (4%). The FSE technique was preferred overall in 54% of
      the joints. Mild to moderate joint effusion was detected in 17 joints because
      additional T2-weighted data were provided with the dual-echo FSE technique. The
      study showed that FSE imaging is an effective technique for evaluation of the
      TMJ. It is faster and diagnostically comparable to or better than CSE imaging,
      with the added advantage of providing T2-weighted data.

PMID- 7633107
TI  - Cardiac-gated MR angiography of pulsatile flow: k-space strategies.
AB  - Signal strength in time-of-flight magnetic resonance (MR) angiography of
      pulsatile flow is modulated by the time-varying intraluminal magnetization
      strength. The specific appearance of MR angiographic images therefore depends on
      the relationship of different phase-encoding steps to the pulsatile flow
      waveform. Cardiac-phase gating can be applied with phase-encoding reordering to
      acquire different regions of k-space during the desired phases of the cardiac
      cycle. The authors have developed a simulation program for evaluating the merits
      of different encoding strategies for pulsatile flow. The model was validated with
      phantom studies. High signal intensity relative to that in conventional MR
      angiographic studies can be attained with strategies that impose relatively small
      penalties in total acquisition time.

PMID- 7633108
TI  - Multislab three-dimensional T2-weighted fast spin-echo imaging of the
      hippocampus: sequence optimization.
AB  - Three-dimensional (3D) fast spin-echo (FSE) imaging can produce contiguous thin
      sections for high-quality multiplanar reconstructions. Such reformatted images
      may be useful in the evaluation of three-dimensionally complex, curvilinear
      anatomic structures such as the hippocampus. The authors describe a 3D FSE
      protocol for T2-weighted imaging of the hippocampus. The protocol uses an
      overlapping-multiple-slab imaging strategy to decrease imaging times and a
      modified refocusing radio-frequency pulse train to improve the reformatted
      images. The authors describe their parameter optimization, discuss the benefits
      and limitations of the new sequence, and present representative images of healthy
      volunteers.

PMID- 7633109
TI  - Fast three-dimensional time-of-flight MR angiography of the intra-cranial
      vasculature.
AB  - Magnetic resonance angiography is most commonly performed with the three
      dimensional (3D) time-of-flight (TOF) technique. As currently practiced, this
      requires long image acquisition times (5-10 minutes). The authors show that the
      acquisition time of 3D TOF images can be reduced to less than 1 minute by using a
      very short TR (< 10 msec). Under normal flow conditions, the major vessels of the
      circle of Willis were consistently well demonstrated on these fast 3D TOF images.
      Signal saturation was observed in studies of patients with abnormal blood flow.
      In those cases, it was demonstrated that serial acquisition of fast 3D TOF data
      during and after contrast agent administration could be used to overcome the
      saturation effects. Time-resolved fast 3D TOF imaging during and after contrast
      agent administration can also provide qualitative assessment of flow and may
      depict other features that cannot be observed in TOF studies with long imaging
      times.

PMID- 7633110
TI  - T2-weighted MR imaging of the chest: comparison of electrocardiograph-triggered
      conventional and turbo spin-echo and nontriggered turbo spin-echo sequences.
AB  - In 22 patients with a diverse range of thoracic abnormalities, T2-weighted
      magnetic resonance (MR) images of the chest were obtained with electrocardiograph
      (ECG)-triggered turbo spin-echo (TSE), ECG-triggered conventional spin-echo
      (CSE), and nontriggered TSE sequences, and the images were compared. A 5-point
      rating scale was used by three radiologists experienced in MR imaging of the
      chest to independently evaluate the images for (a) freedom from ghosting, (b)
      clarity of heart wall and cardiac chambers, (c) clarity of mediastinal
      structures, (d) conspicuity of abnormalities, and (e) overall image quality.
      Evaluations were analyzed with statistical methods. For freedom from ghosting,
      clarity of heart wall and cardiac chambers, clarity of mediastinal structures,
      and overall image quality, the ECG-triggered TSE images were rated higher than
      the TSE images, which, in turn, were rated higher than the ECG-triggered CSE
      images at the P = .05 level of significance. No significant differences were seen
      between the pulse sequences in the conspicuity of abnormalities, although some
      differences were observed in individual cases. Our results suggest that ECG
      triggered TSE imaging provides improved, time-efficient T2-weighted images of the
      chest.

PMID- 7633111
TI  - Validation of cine phase-contrast MR imaging for motion analysis.
AB  - The accuracy of cine phase-contrast magnetic resonance (MR) imaging for motion
      analysis was evaluated. By using a rotating phantom and postprocessing algorithm
      for phase tracking, errors arising during data acquisition were identified and
      compensation methods were developed. A spatially varying background phase offset
      in the velocity images was found to be due to eddy current-induced fields. The
      magnitude of the offset was in the range of 0-20 cm/sec, which is of the same
      order of magnitude as cardiac contractile velocities. Background offset is thus
      an important source of error in tracking cardiac motion. Study of different
      tracking algorithms revealed the need for an integration scheme using motion
      terms higher than velocity. Also, considerable improvement in the accuracy and
      stability of the predicted trajectories was obtained by averaging the
      trajectories proceeding both forward and backward in time from the starting
      point. With the algorithm developed, the motion of the phantom was tracked
      through a complete rotation of the phantom to an accuracy of 2 pixels.

PMID- 7633112
TI  - Tracking of cyclic motion with phase-contrast cine MR velocity data.
AB  - A method of computing trajectories of objects by using velocity data,
      particularly as acquired with phase-contrast magnetic resonance (MR) imaging, is
      presented. Starting from a specified location at one time point, the method
      recursively estimates the trajectory. The effects of measurement noise and eddy
      current-induced velocity offsets are analyzed. When the motion is periodic,
      trajectories can be computed by integrating in both the forward and backward
      temporal directions, and a linear combination of these trajectories minimizes the
      effect of velocity offsets and maximizes the precision of the combined
      trajectory. For representative acquisition parameters and signal-to-noise ratios,
      the limitations due to measurement noise are acceptable. In a phantom with
      reciprocal rotation, the measured and true trajectories agreed to within 3.3%.
      Sample trajectory estimates of human myocardial regions are encouraging.

PMID- 7633113
TI  - Segmentation of small structures in MR images: semiautomated tissue hydration
      measurement.
AB  - Segmentation of small anatomic structures in noisy magnetic resonance (MR) images
      is inherently challenging because the edge information is contained in the same
      high-frequency image component as the noise. The authors overcame this obstacle
      in the analysis of the sural nerve in the ankle by processing images to reduce
      noise and extracting edges with an edge detection algorithm less sensitive to
      noise. Anatomic accuracy of the segmentation was confirmed by a neuroradiologist.
      A nerve hydration coefficient was determined from the signal intensity of the
      nerve in these segmented images. These semiautomated measurements of hydration
      agreed closely with those obtained with a previously described manual method (n =
      44, P = .76). Each image in the study was analyzed identically, with no
      modification of the computer algorithm parameters. The data suggest that this
      robust method may be useful in a multicenter evaluation of diabetes treatment
      protocols.

PMID- 7633115
TI  - Errors in quantitative dynamic three-dimensional keyhole MR imaging of the
      breast.
AB  - Three-dimensional (3D) keyhole magnetic resonance (MR) imaging has been proposed
      as a means of providing dynamic monitoring of contrast agent uptake by breast
      lesions, with complete breast coverage and high spatial and temporal resolution.
      The 3D keyhole technique dynamically samples the central regions of k-space in
      both phase-encoding directions and provides high-frequency data from a
      precontrast acquisition. Errors due to data truncation with two-dimensional and
      3D region-of-interest measurements are estimated from a numerical simulation of
      various implementations of the 3D keyhole technique. Errors were found to
      increase with increasing temporal resolution and reduced object size. Errors of
      75% are possible for objects with a diameter approaching 1 pixel when a 3D
      keyhole implementation that samples 50% of phase-encoding data in each direction
      is used. Preliminary clinical images with this approach illustrate artifacts
      consistent with inadequate k-space sampling.

PMID- 7633114
TI  - Vessel enhancement filtering in three-dimensional MR angiography.
AB  - For a variety of reasons, small vessels have low signal intensity in magnetic
      resonance angiography. When the vessel signal intensity is lower than the signal
      intensity of background tissues, these vessels tend not to be visible on maximum
      intensity-projection images. The authors developed a nonlinear second-difference
      spatial filtering technique that enhances the details of small vessels while
      suppressing both noise and uniform background tissue. Two similar nonlinear
      second-difference filters are presented and compared with the linear Laplacian
      second-difference filter. To evaluate the performance of these filters, they were
      applied to intracranial three-dimensional time-of-flight MR angiographic data and
      the results compared with the vessel enhancement obtained with a simple second
      difference Laplacian filter and with magnetization transfer contrast (MTC)
      techniques. The comparisons demonstrated that nonlinear filtering and MTC
      techniques result in similar improvement in small-vessel visibility and apparent
      continuity. A quantitative comparison demonstrated that the improvement in the
      contrast-to-noise ratio is much greater with the nonlinear filters than the
      Laplacian filter.

PMID- 7633116
TI  - Intracavitary birdcage resonator: applications to the human prostate.
AB  - Twenty-five patients with prostatic cancer were prospectively examined with a
      prototype endorectal surface coil featuring a birdcage resonator circuit design.
      The purpose was to determine the safety of an intracavitary probe for magnetic
      resonance (MR) imaging of the pelvis that incorporates the "inside-out"
      characteristics of a volume coil design and allows high-resolution MR imaging of
      the prostate and potentially serves as an alternative to single-loop
      intracavitary surface coils. Clinically useful images supplementing images
      obtained with the body or external surface coils were obtained with the prototype
      probe. It was tolerated by all patients enrolled in the study, and none
      experienced side effects. The cylindrically symmetric sensitivity profile of the
      probe allowed identification of prostate tumors and pelvic lymph node and bone
      metastases. Volume-type coils may improve endopelvic MR imaging when used alone
      or in combination with external coil systems.

PMID- 7633117
TI  - Biopsy needles and devices: assessment of ferromagnetism and artifacts during
      exposure to a 1.5-T MR system.
AB  - Forty-eight biopsy devices (needles, stylets, guide wires, biopsy guns, etc) were
      evaluated for ferromagnetism (n = 48) and artifacts (n = 43) in a 1.5-T magnetic
      resonance (MR) system, with previously described techniques. Forty-five of the 48
      devices were found to be ferromagnetic. Artifacts varied, depending on the type
      and size of the component material(s) of the device. Most of the commercially
      available biopsy devices are not useful for MR imaging-guided biopsy procedures
      because of the presence of ferromagnetism and associated artifacts.

PMID- 7633118
TI  - On MR imaging of atheromatous lipids in human arteries.

PMID- 7633119
TI  - Late graft failure of autologous vein grafts for arterial occlusive disease:
      clinical and experimental studies.
AB  - Late graft failure following arterial reconstructive surgery, especially after
      infrainguinal reconstruction, remains a major concern for vascular surgeons. To
      more effectively predict the outcome of reconstructed arteries, we herein propose
      an intraoperative flow waveform analysis which correlates well with the long-term
      patency rate of grafts. According to this flow waveform analysis, late graft
      failure was occasionally seen in grafts with type II waveforms when poor distal
      runoff vessels had been shown by the preoperative arteriogram. Next, to
      investigate which events occurring in autologous vein grafts under abnormal
      hemodynamics may contribute to late graft failure, a distal poor-runoff model was
      made in the canine femoral artery. In this review, we present the results of our
      investigation on autologous vein grafts using this poor-runoff model. We also
      relate our recent findings on the function of regenerated endothelium in
      autologous vein grafts.

PMID- 7633120
TI  - Factors related to impaired bactericidal activity in patients with esophageal
      cancer.
AB  - We examined the possible factors that could contribute to the impairment of
      polymorphonuclear neutrophil (PMN) bactericidal activities in patients with
      esophageal cancer, based on the discovery that a depression of the intracellular
      killing (KI) activity, with an elevation of the superoxide anion-producing
      capacity (SOP), of PMN is associated with the occurrence of infectious
      complications following surgery for esophageal cancer. KI, SOP, and
      myeloperoxidase (MPO) activity were measured in 30 patients with esophageal
      cancer and 33 patients with gastric cancer. Sex, age, and cancer stage were not
      significantly associated with impaired bactericidal activities; however,
      malnutrition was significantly correlated with both a depression in KI (r = 0.58,
      P < 0.001) and an elevation in SOP (r = -.36, P < 0.05) in the patients with
      esophageal cancer, but not in those with gastric cancer. The incidence of chronic
      obstructive pulmonary disease (COPD) was significantly higher in the esophageal
      cancer patients whose SOP was elevated, at 39% versus 0% (P < 0.05). These
      results suggest that malnutrition and probably also latent infections associated
      with COPD contribute to the impaired bactericidal activities of PMN in patients
      with esophageal cancer.

PMID- 7633121
TI  - Lymph flow and lymph node metastasis in esophageal cancer.
AB  - This paper delineates which lymph nodes should be dissected due to the high
      frequency of metastasis associated with different types of primarily lesions of
      the thoracic esophagus. In cancer involving the upper third of the esophagus
      (Iu), lymph flow was found to be primary from the superior mediastinal area to
      the cervical area; in that involving the middle third (Im), it was broadly
      distributed from the superior, middle, and inferior mediastinal region to the
      cervical and abdominal regions; and in that involving the lower third (Ei), it
      tended to extend from the inferior mediastinal region to the abdominal region,
      with single primary metastatic nodes also being noted in this area. The
      significance of the "top" nodes, namely, the nodes located along the right
      recurrent laryngeal nerve in the upper portion of the thorax, was also
      investigated, and it was confirmed that the prognosis for patients with
      metastases to both the top nodes and other nodes was unfavorable. An
      immunohistochemical study on mediastinal lymph flow using the anti-Su-Ps antibody
      demonstrated interactions between top nodes and cervical and/or thoracic nodes.

PMID- 7633122
TI  - Changes in surgical strategies for peptic ulcers before and after the
      introduction of H2-receptor antagonists and endoscopic hemostasis.
AB  - A total of 902 surgical patients with peptic ulcer disease were evaluated to
      clarify the effects of H2-receptor antagonists and endoscopic hemostasis on
      surgical treatment. Following the introduction of these treatments to our
      institute in 1982, the number of operations performed annually decreased by 40%,
      or 36 cases per year. However, a remarkable increase in the frequency of surgical
      emergency intervention since 1982 was concurrently observed, with the ratio of
      emergency procedures to the total number of operated cases increasing to 72.5% in
      the last 5 years of the study. Moreover, intractability as an indication for
      surgery decreased to 34.1%, compared with an increase in the number of patients
      with bleeding and perforated ulcers requiring operation. There were 13
      postoperative deaths recorded (1.4%). All of the deaths were in patients who had
      undergone emergency surgery in poor health. Of these 13 patients, 10 had bleeding
      ulcers. A study of bleeding ulcers for which endoscopic hemostasis had been
      unsuccessful revealed that shock on admission and a concomitant medical condition
      had been evident in all the patients who died, and in 52.2% and 30.4% of the
      survivors, respectively. The current study suggests that the frequency of high
      risk patients requiring surgery is increasing since the introduction of H2
      receptor antagonists and endoscopic hemostasis, and thus, prompt surgical
      treatment and intensive management for such patients is essential.

PMID- 7633123
TI  - Metastases to the regional lymph nodes, lymph node recurrence, and distant
      metastases in nonadvanced papillary thyroid carcinoma.
AB  - To investigate the biological characteristics of papillary thyroid carcinoma from
      the perspectives of lymph node metastasis, lymph node recurrence, and distant
      metastasis, 746 patients with nonadvanced papillary thyroid carcinoma were
      retrospectively studied. There were 76 men and 670 women with a mean age of 42.7
      years. The rate of lymph node metastasis was significantly higher in young
      patients (aged less than 30 years). Lymph node recurrence was observed in 80
      patients and distant metastasis in 13, being seen with significant frequency in
      the young and elderly (aged over 50 years) patients and in the men. The frequency
      of distant metastasis was significantly greater in the elderly patients and in
      those with lymph node recurrence. These findings indicate that the role of
      regional lymph nodes and the clinical meaning of lymph node recurrence differ
      between young and elderly patients.

PMID- 7633124
TI  - Histopathological study of local residual carcinoma after simulated lumpectomy.
AB  - From 1989 to 1991, 24 patients with invasive ductal carcinoma underwent simulated
      lumpectomy at Tokyo Women's Medical College Daini Hospital. The mastectomy
      specimens were then examined histopathologically in serial sections for the
      presence of residual tumors or multicentricity. Lumpectomy specimens from cancer
      foci at resected margins were also examined. In this study, 23 of 24 patients
      demonstrated positive resection margins (95.8%). Residual tumors were found in
      mastectomy specimens from 16 patients (66.7%); unilateral multifocal carcinomas
      were found in 2 of these patients (8.3%). The incidence and severity of residual
      tumors did not correlate with primary tumor size or the distance between the
      nipple and the primary tumor but directly correlated with the severity of
      intraductal spread of the primary tumor. Tumors with central necrosis were
      associated with a higher incidence of residual tumors. Our study thus indicates
      that there is a high risk that some residual tumor will be left in the conserved
      breast when lumpectomy is performed. Multifocal carcinoma and tumors showing
      severe intraductal spread and central necrosis are thus associated with extensive
      residual tumors and are likely to cause local recurrence.

PMID- 7633125
TI  - Flow cytometric analysis of the DNA content of thymomas.
AB  - In this study, the prognostic value of determining the nuclear DNA content of
      thymomas by flow cytometry was evaluated. Of a total 31 resected thymomas, 10
      (32%) showed DNA aneuploidy, the presence of which was significantly correlated
      with an advanced clinical stage of disease. The patients with an aneuploid tumor
      had a poorer prognosis than those with a diploid tumor, demonstrating a survival
      rate of 50% at 7 postoperative years, which was considerably less favorable than
      that of the patients with a diploid tumor, being 100% in the same period (p <
      0.05). Moreover, patients with a high DNA index (DI), i.e., a DI >or= 1.5, tended
      to have a poorer prognosis than those with a low DI. These findings indicated
      that the DNA content can be an important prognostic index in patients with
      thymomas.

PMID- 7633126
TI  - The kinetics of copper-zinc superoxide dismutase in experimentally induced
      ischemia-reperfusion injury of the canine jejunum.
AB  - In this study, the kinetics of copper-zinc superoxide dismutase (CuZn-SOD) in
      experimentally induced ischemia-reperfusion injury of the canine jejunum were
      examined using immunohistochemical procedures, and evaluated as an index for the
      viability of transplants. A pedicled jejunal graft was subjected to arterial
      reperfusion after clamping the supplying blood vessels for 30 min. Under
      nonischemic conditions, some of the goblets in the goblet cells and the mucin
      covering the surface of the villi were stained positively with luxol fast blue,
      von Kossa, and immunohistochemistry for CuZn-SOD. Between 5 and 30 min after
      reperfusion, the appearance of goblets with positive immunoreaction for CuZn-SOD
      in the intestinal glands and the disappearance of these goblets in the villi were
      observed in the grafts of animals that received arterial reperfusion after 30 min
      of clamping of the arteries and veins at room temperature. Thereafter, the former
      disappeared gradually and the latter returned toward the nonischemic condition.
      The administration of allopurinol led to a decrease in tissue damage and a
      significantly higher number of goblets with positive immunoreaction for CuZn-SOD
      than in untreated animals. Furthermore, the goblets in the intestinal glands
      showed a negative reaction for CuZn-SOD 5 to 30 min after reperfusion.
      Preservation at 4 degrees C during ischemia revealed similar results to those
      observed in the animals given allopurinol. Thus, the distribution and intensity
      of CuZn-SOD positive goblets seems to be a useful indicator for the evaluation of
      tissue damage induced by free radicals mediating ischemia-reperfusion injury.

PMID- 7633127
TI  - The platelet activating factor as a pivotal mediator of shock after liver
      ischemia.
AB  - Liver failure is often accompanied by shock, which is usually refractory to
      conventional vasopressive therapy, and it is believed that some potent chemical
      mediators are involved in this process. The platelet activating factor (PAF) is a
      newly discovered inflammatory mediator that has a remarkable hypotensive action.
      In the present study, the possible role of PAF in shock after ischemic liver
      failure was investigated. Partial hepatic ischemia was induced in Wistar rats by
      clamping the hepatic afferent vessels to almost 70% of the whole liver for 90
      min. One group of rats was pretreated with 10 micrograms/kg of TCV-309, a PAF
      antagonist. Pretreatment with TCV-309 inhibited the shock that ultimately
      occurred in the untreated rats; the survival rate 16 h after hepatic ischemia was
      20% in the untreated control group but 100% in the group pretreated with TCV-309.
      The level of PAF in the plasma after hepatic ischemia was 2,939 +/- 2,412 pg/ml,
      which was significantly higher than that of the surgical control (920 +/- 188
      pg/ml). These findings strongly suggest that anoxical disintegration of the liver
      derives PAF which causes shock. Thus, a PAF antagonist is expected to be an
      effective prophylactic treatment for patients who are at risk of developing shock
      from an ischemic liver.

PMID- 7633128
TI  - Effective treatment of liver metastases from colon cancer with a combination of
      gamma-interferon and cisplatin chemotherapy: report of a case.
AB  - We report herein the case of a 63-year-old man with cancer of the sigmoid colon
      and metastatic nodules in the liver who was effectively treated with a
      combination of cisplatin regional chemotherapy, given through the hepatic artery,
      in conjunction with a 3-week course of intravenous gamma-interferon (INF-gamma),
      following palliative sigmoidectomy and dissection of the regional lymph nodes.
      This was followed-up by a 3-month course of oral 5-fluorouracil. Hepatic imaging
      performed 6 months postoperatively showed no masses in the right hepatic lobe and
      an apparent decrease in the size of the tumor in the left lobe. A second-look
      operation with resection performed at this time confirmed the efficacy of the
      chemotherapy. The patient survived in excess of 30 months following his initial
      surgery before succumbing to hepatic failure.

PMID- 7633129
TI  - Gas-forming liver abscess following transcatheter hepatic arterial embolization
      for an iatrogenic intrahepatic pseudoaneurysm: report of a case.
AB  - We herein describe a case of gas-forming pyogenic liver abscess following
      transcatheter hepatic arterial embolization (THAE) for an iatrogenic intrahepatic
      pseudoaneurysm in a 74-year-old woman. Hemobilia developed 19 days after
      percutaneous transhepatic cholangio-drainage was performed for the purpose of
      percutaneous cholangioscopic lithotripsy for the treatment of post-gastrectomy
      choledocholithiasis. Celiac arteriography disclosed a saccular aneurysm in the
      right hepatic artery. The pseudoaneurysm was successfully occluded by THAE with
      gelatin powder and a stainless steel coil of the Gianturco type. Ten days after
      successful THAE, abdominal computed tomography revealed a gas-containing cavity,
      which suggested the presence of a gas-forming abscess, in the posterior hepatic
      segment, and percutaneous transhepatic abscess drainage was performed. Thus,
      impaired hepatic perfusion following effective THAE and coexisting cholangitis
      may play an important role in the development of a gas-forming pyogenic liver
      abscess.

PMID- 7633130
TI  - Abdominal tuberculoma mimicking a pancreatic neoplasm: report of a case.
AB  - We report herein a case of clinically solitary abdominal tuberculoma. A 28-year
      old woman was admitted to hospital for treatment of an abdominal tumor shown to
      be located in the head of the pancreas and compressing the superior mesenteric
      vein by echosonography and computed tomography (CT). There were no clinical signs
      or symptoms of tuberculosis in the lungs or abdomen. Thus, under the diagnosis of
      a neoplasm of the pancreas, an exploratory laparotomy was performed which
      revealed tuberculosis. The patient made an excellent recovery on anti-tuberculous
      treatment, and no evidence of a tumor was seen on a CT scan performed 6 months
      after the initiation of treatment. Abdominal tuberculoma is often mistaken for a
      malignant neoplasm and the nonsurgical diagnosis of this entity continues to be a
      challenge.

PMID- 7633131
TI  - A case of encapsulated noninvasive thymoma (stage I) with myasthenia gravis
      showing metastasis after a 2-year dormancy.
AB  - We herein describe a case of thymoma in which metastasis to the left lower
      visceral and parietal pleura was noticed after a 2-year dormancy. A closer
      examination revealed no evidence that the metastatic tumors were of lymph node
      origin. The initial thymoma was well encapsulated, and thus it was thought that
      the development of metastasis might have reflected a sudden rapid growth of the
      thymoma cells after a 2-year period of inactivity.

PMID- 7633132
TI  - Treatment of a giant coronary artery aneurysm in an adult with a history of
      Kawasaki disease by resection and bypass grafting: report of a case.
AB  - We report herein the case of a 22-year-old man with a history of Kawasaki disease
      who developed a giant calcified aneurysm of the left main coronary artery. The
      aneurysm was successfully resected and coronary bypass surgery was performed
      using the bilateral internal thoracic arteries. The resected aneurysm, the
      maximal diameter of which was 27 mm, showed heavy calcification of the inner
      layer and extended into the adjacent coronary arteries, producing a significant
      narrowing of the lumen of both the left main trunk (50%) and the anterior
      descending branch (50%). Extensive intimal calcification presumably prevented
      normal luminal development and produced a significant narrowing as the patient
      grew into adulthood. A cause for stenotic lesions developing in the coronary
      artery adjacent to a coronary aneurysm in adults with a history of Kawasaki
      disease is suggested here by the resected aneurysm seen in this patient. Thus,
      adult patients with giant coronary artery aneurysms and significant stenotic
      lesions of the coronary artery associated with Kawasaki disease may require
      aneurysmectomy in addition to bypass surgery.

PMID- 7633133
TI  - Portal vein reconstruction using an internal jugular vein as a graft: report of a
      case.
AB  - We report the case of a 41-year-old man with pancreatic carcinoma invading the
      portal vein who was successfully treated by portal vein resection combined with
      pancreatoduodenectomy and reconstruction using an autointernal jugular vein. The
      internal jugular vein is an ideal graft for portal vein replacement because it
      has sufficient length, a well-matched diameter, and there is no venous
      insufficiency after unilateral resection. Nevertheless, this is the first report
      of portal vein reconstruction using the internal jugular vein as a graft.

PMID- 7633134
TI  - Esophagoaortic fistula caused by esophageal tuberculosis: report of a case.
AB  - We report herein the case of a 73-year-old woman who was urgently admitted to
      hospital with severe hematemesis. An emergency endoscopy revealed a protruding
      lesion 36 cm from the incisors; however, respiratory insufficiency precluded
      surgery and despite aggressive medical treatment, the patient's respiratory
      status continued to deteriorate, leading to death on the 36th hospital day. An
      autopsy revealed the source of the hemorrhage to be a fistula connecting the
      esophagus and the descending aorta. Histopathologic studies showed that this
      fistula was caused by esophageal tuberculosis.

PMID- 7633135
TI  - Left atrial plication combined with mitral valve surgery in patients with a giant
      left atrium.
AB  - The benefits of performing left atrial plication during mitral valve surgery for
      patients with a giant left atrium were evaluated by analyzing the short- and long
      term surgical results and changes in the left atrial dimension (LAD) and
      respiratory function of 30 patients. Of the 30 patients, 2 (7%) died of multiple
      organ failure on postoperative days 26 and 117, but no other deaths occurred
      during the mean follow-up of 5.9 +/- 2.1 years. Valve thrombosis was observed in
      one patient and cerebral complications with no residual deficit were observed in
      two patients, with a 9-year event-free rate of 87 +/- 7%. The LAD decreased
      significantly from 69.0 +/- 8.5 mm to 53.7 +/- 9.1 mm (P < 0.01) shortly after
      surgery, and this decreased was maintained even 5 years after surgery (53.3 +/-
      11.4 mm). The cardiothoracic ratio decreased from 74.8 +/- 8.3% to 62.8 +/- 9.0%
      (P < 0.01) and the vital capacity of the lungs increased from 71.1 +/- 18.0% to
      82.9 +/- 22.2% (P < 0.01). Thus, we conclude that performing left atrial
      plication during mitral valve surgery is safe and effective for patients with
      giant left atrium.

PMID- 7633136
TI  - Examining breast feeding performance: forgotten influencing factors.

PMID- 7633137
TI  - Separation distress call in the human neonate in the absence of maternal body
      contact.
AB  - Few studies have used the baby's cry as a means of evaluating the quality of
      neonatal care. In this randomized trial the newborn's cry was registered during
      the first 90 min after birth when infants were cared for either: (a) skin-to-skin
      with the mother; (b) in a cot; or (c) in a cot for the first 45 min of the 90-min
      observation period and then skin-to-skin with the mother. The results suggested
      that human infants recognize physical separation from their mothers and start to
      cry in pulses. Crying stops at reunion. The observed postnatal cry may be a human
      counterpart to the "separation distress call" which is a general phenomenon among
      several mammalian species, and serves to restore proximity to the mother. Our
      results suggest that in human newborns this cry is not dependent on earlier
      social experience and may be a genetically encoded reaction to separation. The
      findings are compatible with the opinion that the most appropriate position of
      the healthy full-term newborn baby after birth is in close body contact with the
      mother.

PMID- 7633138
TI  - Effect of body tilting on physiological functions in healthy term neonates.
AB  - The effect of body tilting on physiological functions was studied in 32 healthy,
      full-term neonates at 2 and 24 h of age. The neonates were placed in the supine
      position and the physiological functions were measured in the sequence of -30
      degrees (head-down), 0 degree and 30 degrees (head-up) tilts. Arterial oxygen
      saturation and respiratory rate were comparable in the vaginal delivery and
      caesarean section groups. The baroreceptor responses were similar in the neonates
      delivered vaginally and by caesarean section. Mean heart rate increased on 30
      degrees up tilting and the responses tended to be larger at 24 h compared with
      those at 2 h of age, but these differences were not significant. At 2 h of age,
      mean systolic and diastolic blood pressures decreased on 30 degrees up tilting.
      At 24 h of age, mean systolic and diastolic pressures decreased on up tilting
      (from -30 degrees to 0 degree) and the values were sustained on further up
      tilting (from -0 degree to 30 degrees). The present results indicate that
      baroreceptor reflexes are present from birth and the responses tend to be less
      developed at 2 h than those at 24 h of age.

PMID- 7633139
TI  - Subsequent pregnancy affects nutritional status of previous child: a study from
      Bhutan.
AB  - In a rural area of Bhutan, anthropometric measurements of 113 children and
      interviews with their mothers were carried out monthly for 32 months. The purpose
      of the study was to investigate the effect of a mother's subsequent pregnancy on
      growth in weight of her last-born child. The children whose mothers had a
      subsequent birth interval of 18-30 months were matched for date of birth with
      children whose mothers did not become pregnant. Growth of the children during the
      subsequent pregnancy was compared with growth during the same period of children
      whose mothers were not pregnant. A statistically significant reduction of 28% was
      found (p < 0.05), which was most pronounced in early pregnancy. A similar trend
      was found for change in mid-upper-arm circumference (p < 0.05). The study
      provides evidence of a causal relationship between a moderate subsequent
      pregnancy interval and a concurrent reduction in growth rate for the previous
      child.

PMID- 7633140
TI  - Development of sleep-wakefulness rhythm in premature babies.
AB  - The aims of this study were: (1) to investigate the evolution of the sleep
      pattern in preterm newborns during their first month of life; (2) to assess the
      influence of light-dark on the sleep pattern; and (3) to compare this pattern
      with that of full-term newborns. The population consisted of 60 healthy, preterm
      newborns and 63 full-term newborns, divided into four age groups, 1 week apart,
      throughout the first month of life. Preterm newborns were further divided into
      five groups according to conceptional (corrected) age. An observer took note
      every 30 min, for 24 h, of sleep or wakefulness in every case. The average
      sleeping time in preterm groups according to postnatal age remained unchanged
      during the first month of life: 17.57 h on day 1 and 17.15 h on day 28. When the
      preterm infants were re-grouped according to conceptional age, average daily
      sleep was 17.86 h at 32 weeks and 15.22 h at 37 weeks. The full-term newborns had
      an average daily sleep of 14.78 h on day 1 and 11.94 h on day 28, with a decrease
      throughout week 4 of life (p < 0.001). The decrease in daily sleeping time in the
      full-term groups, took place at the expense of the daylight span, where there was
      a decrease throughout the first month of life (p < 0.01). There were no
      differences in preterm newborns during the light and dark phases. A progressive
      synchronization of sleep to the light-dark was seen in the control
      group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7633141
TI  - Urinary excretion of aldosterone, arginine vasopressin and cortisol in premature
      infants with maximum renal acid stimulation.
AB  - Of 452 low-birth-weight infants who were routinely screened for maximum renal
      acid stimulation (MRAS) (urine pH < 5.4), 149 episodes of incipient late
      metabolic acidosis (urine pH < 5.4 on 2 consecutive days) were randomly allocated
      to either a control group or treatment with NaHCO3 or NaCl (2 mmol/kg/day each)
      for 7 days. Urinary excretion of aldosterone-18-glucuronide (Aldo), arginine
      vasopressin (AVP) and cortisol was determined in timed urine samples. On day 1,
      patients with MRAS showed a tendency towards increased urinary excretion of Aldo
      compared with infants without MRAS. In patients who received alkali therapy,
      urinary excretion of Aldo, AVP and cortisol decreased or showed a trend to lower
      values from day 1 to day 7, whereas in patients with MRAS but no specific
      therapy, Aldo and AVP showed a tendency to increase. We concluded that persistent
      MRAS is not only characterized by a reduced rate of weight gain and a tendency to
      decreased nitrogen assimilation, but also increased secretion of Aldo and AVP.

PMID- 7633142
TI  - Brain lactate in preterm and growth-retarded neonates.
AB  - Glucose is the predominant cerebral energy source under physiological conditions,
      although other substrates may support cerebral metabolism. The present study was
      undertaken to determine if lactate is present in the immature human brain, and if
      so, whether or not concentrations of lactate differ between small-for-gestational
      age and appropriate-for-gestational-age infants. Thirty stable, healthy infants
      with normal brains were investigated. As the only nutrient, all received milk
      enterally prior to the investigation, which was carried out without sedation.
      Mean gestational age was 35 completed weeks (range 28-41 weeks) and mean birth
      weight was 2170 g (range 855-4100 g). Proton nuclear magnetic resonance spectra
      from the striatal region were obtained while the infants were sleeping quietly.
      Lactate was present in all 10 preterm small-for-gestational-age and 10 of 13
      preterm appropriate-for-gestational-age infants, and the concentration was
      inversely related to postmenstrual age (p < 0.002). In addition, lactate
      increased with the degree of growth retardation (p < 0.01). At present the
      significance of lactate is unclear. Lactate may be produced locally or in
      peripheral tissues, and may support brain metabolism.

PMID- 7633143
TI  - Extremely low-birth-weight infants less than 901 g: development and behaviour
      after 4 years of life.
AB  - In a long-term, prospective, control study, 20 extremely low-birth-weight (ELBW)
      infants with birth weights between 500 and 900 g (mean 755 (SD 109) g) and
      gestational ages between 24 and 30 weeks (mean 26.2 (SD 1.8) weeks) were compared
      with 20 full-term infants at 4 years of age for growth, health, development and
      quality of life. Four of 20 (20%) ELBW children had major neurological disorders,
      which were all identified at the 1-year assessment. Seventeen (85%) ELBW children
      had cognitive development, assessed with the Griffiths mental development scale,
      within the normal range for age but lower than for full-term controls. The
      greatest deviations between ELBW and full-term children were found in locomotor
      and visual-motor integration functions. Eight ELBW children in all (40%), four
      with recurrent respiratory tract infections after neonatal mechanical ventilation
      and the four children with major neurological disorders had a higher rate of
      visits to physicians and hospital admissions. The behavioural symptom interview
      showed an increased rate of hyperactivity and difficulties in concentrating but
      not of general behavioural deviations in the ELBW group. Only by school age can
      all aspects of an extremely early birth be evaluated, but at 4 years of age, 85%
      of the ELBW children in our group had a good quality of life according to
      Scheffzek's categorizations.

PMID- 7633144
TI  - Release of xanthine oxidase to the systemic circulation during resuscitation from
      severe hypoxemia in newborn pigs.
AB  - Xanthine oxidase may contribute to oxygen free radical formation during
      reoxygenation after hypoxia, but in humans the enzyme is present in substantial
      amounts only in the liver and intestine. We developed a sensitive assay for
      xanthine oxidase using 14C-xanthine as substrate and investigated whether
      xanthine oxidase was released into the systemic circulation when 19 newborn pigs
      were resuscitated after severe hypoxemia. In five piglets plasma xanthine oxidase
      concentrations increased from undetectable levels to a median value of 8 (range 4
      18) microU/ml after 30 min of reoxygenation. In these pigs serum aspartate
      aminotransferase increased from 45 to 148 U/l, while alanine aminotransferase was
      unchanged (28-31 U/l). The release of xanthine oxidase did not seem to correlate
      with the severity of the histological brain damage after 4 days. We conclude that
      only low levels of xanthine oxidase are released to the systemic circulation
      after severe hypoxemia in newborn pigs.

PMID- 7633145
TI  - Healthy eating for infants--mothers' attitudes.
AB  - Mothers' perceptions of desirable nutritional practices in infant feeding were
      examined using a questionnaire consisting of open and closed questions. A total
      of 1004 mother-infant pairs were recruited from a mixture of urban and rural
      areas in England. The sample represented a cross-section of socioeconomic groups
      and educational backgrounds. Mothers' attitudes to healthy eating for infants
      revealed some misconceptions; 83% felt that a high fibre intake was important or
      very important and 87% that a low fat intake was important or very important,
      while 20% considered that plenty of calories was not important. Other health
      guidelines were appropriately applied and most mothers considered a wide variety
      of foods, plenty to drink and a low sugar and salt intake to be important. These
      beliefs were representative of the sample population, irrespective of the
      socioeconomic group, location, age and education of the mother.

PMID- 7633146
TI  - Polyunsaturated fatty acids in erythrocyte and plasma lipids of children with
      severe protein-energy malnutrition.
AB  - The fatty acid composition of plasma cholesterol esters, plasma phospholipids,
      erythrocyte phosphatidylcholine and erythrocyte phosphatidylethanolamine was
      investigated in severely malnourished Nigerian children with kwashiorkor (n = 12)
      and marasmus (n = 32). Normally nourished children from the same area (n = 23)
      served as controls. The malnourished children showed a significant reduction of
      highly polyunsaturated fatty acids in cholesterol esters, phospholipids and
      phosphatidylcholine. No differences between the groups were found in erythrocyte
      phosphatidylethanolamine. Children with kwashiorkor had lower levels of linoleic
      acid metabolites and docosahexaenoic acid than marasmic children. The results
      suggest that the kwashiorkor syndrome is associated with impaired desaturation
      and elongation of PUFA and/or increased lipid peroxidation.

PMID- 7633147
TI  - Comparison of different indices of dietary control in phenylketonuria.
AB  - Ten different indices of dietary control (IDCs) applied frequently to investigate
      compliance of phenylketonuric patients were calculated for a set of blood
      phenylalanine levels for 98 patients in the German Collaborative Study of
      Children Treated for Phenylketonuria during their first 9 years of life. The
      results were compared for similarities and differences. Cluster analysis of
      longitudinal phenylalanine data was introduced to analyse phenylalanine blood
      levels independent of a priori defined criteria of classification. Three groups
      of good, intermediate and poor long-term dietary control were identified.
      Internal validation of the IDCs was corroborated by the high inter-correlations
      of the indices. External validity was determined by the inter-relations of the
      WISC-R IQ and the IDCs. The different algorithms of IDCs suggest different
      clinical conclusions. To facilitate comparisons of results of future research,
      IDCs should be standardized.

PMID- 7633148
TI  - The nutritional response to home enteral nutrition in childhood.
AB  - The nutritional response to home enteral nutrition (HEN) was evaluated in a
      prospective study of 44 consecutive children (median age 48 months) who received
      HEN for more than 1 month (median duration 6 months). Three groups were studied:
      17 children were stunted, 14 were wasted and 13 were adequately nourished but
      unlikely to maintain oral intake during anticipated nutritional stress. In the
      stunted group (median duration of HEN 15 months) there was a significant
      correlation between improvements in height-for-age z scores and duration of feeds
      (r = 0.63; p = 0.006). In the wasted group (median duration of HEN 4 months) all
      anthropometric indices improved significantly (p < 0.05). HEN was also successful
      in maintaining nutritional status in the third group. Thus, supplementary HEN is
      an effective method of nutritional support for a variety of indications, provided
      concurrent advice from a nutritional care team is available.

PMID- 7633149
TI  - Relationship between height, sitting height and subischial leg length in Dutch
      children: presentation of normal values.
AB  - A widely used method of judging body proportions is to consider the ratio of
      sitting height to height (SH/H) related to age. A drawback of this method is that
      only one derived variable is used. A pairwise consideration of the original
      measurements provides more information. In this study data from the cross
      sectional Oosterwolde I growth study are used to present normal values for the
      ratio SH/H for age, as well as values for sitting height related to height and
      subischial leg length. A comparison is made with other studies.

PMID- 7633150
TI  - Pelvic ultrasound measurements in normal girls.
AB  - Pelvic ultrasound scans were carried out in 153 normal girls aged between 3 days
      and 14.9 years, in order to obtain reference data for ovarian volume, uterine
      length and uterine configuration. The right ovary was significantly larger than
      the left (by about 17%). Ovarian volume increased exponentially with age, over
      this age range. No relationship with pubertal stage (independent of age) could be
      demonstrated. Uterine length decreased from birth to 4 years, before steadily
      increasing. The fundal-cervical ratio (FCR) decreased initially then increased to
      lie above 1.0 by 15 years of age. A midline endometrial echo was seen in half of
      the subjects aged less than 6 months, but otherwise it was not seen before 11.8
      years of age or at Tanner stage B2. Smoothed reference centile curves for uterine
      length, right and left ovarian volume were produced, allowing z scores (or SD
      scores) to be calculated for each measurement.

PMID- 7633151
TI  - Pelvic ultrasound findings in different forms of sexual precocity.
AB  - Recently produced reference curves for various ultrasound dimensions were used to
      retrospectively assess 67 pelvic ultrasound scans carried out at the initial
      presentation in girls with sexual precocity. At presentation the group with
      precocious puberty had significantly increased uterine lengths and ovarian
      volumes compared with the normal population, and a significantly increased fundal
      cervical ratio. Ovarian volume was also significantly increased in therlarche and
      thelarche variant. The fundal-cervical ratio was significantly increased in
      thelarche variant. There was considerable overlap between individuals with sexual
      precocity and normal subjects. The ultrasound findings that best discriminated
      early or precocious puberty from other forms of sexual precocity were the
      presence of a midline endometrial echo, and a uterine length above the 97th
      centile for age. An entirely normal pelvic ultrasound at presentation did not
      rule out the possibility of precocious puberty.

PMID- 7633152
TI  - Final height of girls with Turner's syndrome: correlation with karyotype and
      parental height.
AB  - Final height of 75 adults with Turner's syndrome (45 Israeli, 30 Italian), never
      treated with GH, was examined to see if a relationship with karyotype patterns
      and parental height existed. Patients were divided into five groups according to
      their chromosome pattern, as follows: group A = 45, X karyotype (34 patients);
      group B = mosaicism (11 with karyotype 45,X/46,XX and 7 with karyotype
      45,X/46,XY); group C = deletion of all or part of Xp (19 patients); subgroup C1 =
      6 with complete deletion of Xp; subgroup C2 = 9 with mosaicism 45,X/46,X,i(Xq);
      subgroup C3 = 4 with 45,X/46,X,ring(X); group D = deletion of Xq (4 patients);
      pure gonadal dysgenesis (PGD) group = 9 patients with pure 46,XX gonadal
      dysgenesis. No statistical difference was noted between the mean height of the
      two national populations studied (Italian 142.2 +/- 5.7 and Israeli 143.0 +/- 7.2
      cm). The mean heights of group D (148.9 cm; range 147-166.2) and the PGD group
      (156.0 cm; 141-171.5) were found to be significantly higher than those observed
      in groups A, B and C (p < 0.03, p < 0.02 and p < 0.02, respectively), even though
      gonadal distinction existed in all five groups. Subgroup C1, where a deletion of
      the entire Xp segment [46,X,i(Xq)] was present, was found to be the shortest
      group (median height 134.5; range 131.9-138 cm).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7633154
TI  - Auxological, clinical and neuroradiological findings in infants with early onset
      growth hormone deficiency.
AB  - Sixteen infants less than 2 years of age with apparently idiopathic
      hypopituitarism were studied. At birth, 11 of 16 patients (69%) had subnormal
      length associated with relative adiposity and 10 of 16 (62%) showed significant
      deterioration in length deficiency from birth onwards. These findings suggest
      that: (a) growth hormone deficiency, in a number of patients, had started well
      before delivery; (b) growth hormones may play a role in intrauterine growth; and
      (c) growth hormone may also be involved in early postnatal growth. Magnetic
      resonance imaging in these patients was very similar to that described in
      hypopituitarism of later onset. This suggests that even in the latter case,
      hypopituitarism may have a prenatal onset. Finally, the severity of growth
      failure and the coexistence of other hypopituitary symptoms at the time of
      diagnosis in 31% of our patients indicate that early clinical screening of
      hypopituitarism is possible.

PMID- 7633153
TI  - Safety of ciprofloxacin therapy in children: magnetic resonance images, body
      fluid levels of fluoride and linear growth.
AB  - We evaluated the safety of ciprofloxacin administered in a dose of 15-25 mg/kg
      for 9-16 days, in a case series of 58 children who were between 8 months and 13
      years of age. No arthropathy was observed during therapy and follow-up. Blinded
      evaluation of 22 pairs of nuclear magnetic resonance scans obtained before and
      between day 10 and 15 of therapy did not reveal any cartilage damage. After the
      first dose of ciprofloxacin (10 mg/kg), serum fluoride levels increased at 12 h
      in 15 of 19 (79%) patients; 24-h urinary fluoride excretion was higher on day 7
      compared with basal values in 16 of 18 (88.9%) patients. Height z scores of 53
      patients at a mean of 22.5 months of follow-up were not significantly different
      from basal scores (p = 0.12). In conclusion, ciprofloxacin may be recommended for
      use in children for short duration when effective alternative antibacterials are
      unavailable. However, there is a need for further studies to evaluate the tissue
      accumulation of fluoride and its potential to cause toxic effects.

PMID- 7633155
TI  - Bacterial colonization of the larynx and trachea in healthy children.
AB  - Fifty healthy children were included in the study; tracheal and laryngeal
      aspirations were performed after oral endotracheal intubation during minor
      surgery. The aspirates were evaluated and examined in the same way as aspirates
      from children suspected of pneumonia; 31 samples were accepted for the final
      analysis. After culturing, specimens from 30 children exhibited growth of
      potential pathogenic bacteria either from the larynx, the trachea or both. Prior
      to culture, bacteria were seen by microscopy in 24 samples from 30 children.
      These results indicate that the majority of healthy children carry potential
      pathogenic bacteria, not only in the larynx but also to a certain extent in the
      trachea. We conclude that aspirates from the larynx and the trachea are of
      limited value in the diagnosis of bacterial pneumonia in children.

PMID- 7633156
TI  - Cardiac arrhythmias mimicking primary neurological disorders: a difficult
      diagnostic situation.
AB  - Cardiac arrhythmias can present with the signs and symptoms of a seizure
      disorder. This potentially life-threatening underlying cause of non-febrile
      seizures should be recognized early, since successful specific treatment is
      possible. The purpose of this retrospective study was to examine common features
      in such patients. Over a period of 25 years, eight patients were initially
      treated for up to 5 years at our institution for a seizure disorder until
      dysrhythmia as the underlying cause of the seizures was disclosed. The main
      symptom was drop attacks coinciding with physical activity or emotional stress.
      Convulsions were only rarely observed. In five of the eight patients the
      underlying disorder was the long-QT-syndrome (Romano-Ward syndrome). In one
      patient intermittent complete atrioventricular block was found, another patient
      showed ventricular tachydysrhythmia of unknown etiology and the last patient
      suffered from hypertrophic cardiomyopathy.

PMID- 7633157
TI  - Playground accidents.
AB  - To study the causes and sequelae of playground accidents we analysed, in a
      retrospective study, 374 playground accidents. Questionnaires were sent to the
      parents and 103 parents (28%) provided detailed information on the playground
      accidents of their children. Thirty-one percent of the children injured in
      playground accidents sustained fractures of the extremities or concussion of the
      brain. Swings, slides, climbing frames, metal bars and merry-go-round accidents
      accounted for 71% of the 338 playground equipment-related accidents, whereas 36
      accidents (10%) occurred without the use of playground equipment. The majority of
      these accidents were caused by children fighting. Rope-plank-type swings were
      frequently involved in backward falling accidents and 86% of the slide accidents
      were fall accidents. Climbing frames should not be taller than 1.6 m. Further
      efforts are mandatory to create and maintain playgrounds which help children
      develop their skills with a minimal risk to injury.

PMID- 7633158
TI  - Cystic fibrosis, pancreatic sufficiency and distal intestinal obstruction
      syndrome: a report of four cases.
AB  - Distal intestinal obstruction syndrome (DIOS), formerly termed meconium ileus
      equivalent, is usually considered to be unique to cystic fibrosis (CF) patients
      who have steatorrhoea. We report four CF patients without steatorrhoea
      ("pancreatic sufficient") who have had repeated episodes of faecal loading
      indistinguishable from DIOS.

PMID- 7633159
TI  - Thyroid complications, including overt hypothyroidism, related to the use of non
      radiopaque silastic catheters for parenteral feeding in prematures requiring
      injection of small amounts of an iodinated contrast medium.

PMID- 7633160
TI  - Fetal pseudohypoaldosteronism: another cause of hydramnios.
AB  - Pseudohypoaldosteronism (PHA) is a rare hereditary salt-wasting syndrome which is
      caused by decreased renal tubular responsiveness to aldosterone. The syndrome
      consists of hyponatremia, hyperkalemia, dehydration, failure to thrive and
      increased urinary salt loss. A case of PHA was previously described where fetal
      polyuria was the probable cause of hydramnios. We present four new cases of PHA,
      from two families, who were born after pregnancies complicated by severe
      hydramnios and premature labor. We suggest that PHA should be included in the
      differential diagnosis of hydramnios, since appropriate investigations might lead
      to the early diagnosis and treatment of a life-threatening disease.

PMID- 7633161
TI  - Multiple brain abscesses in a premature infant: complication of Staphylococcus
      aureus sepsis.
AB  - We report a premature infant with Staphylococcus aureus sepsis, most probably
      originating from an infected peripheral iv site, and complicated by multiple
      brain abscesses. Diagnosis was made by cranial ultrasonography and computed
      tomography. Since systemic antibiotic treatment failed, surgical drainage was
      performed. The same organism that caused the initial sepsis grew from the
      pyogenic material obtained. The child is currently severely handicapped.

PMID- 7633162
TI  - A managed care provider's approach toward mandated infertility coverage: the
      Illinois Family Building Act.

PMID- 7633163
TI  - Assisted reproduction in Latin America.

PMID- 7633164
TI  - Chromosome investigation in in vitro fertilization failure.
AB  - PURPOSE: A chromosomal complement of 227 human oocytes was studied to provide
      information on the frequency and type of chromosomal abnormalities in oocytes
      failing in vitro fertilization. RESULTS: Normal haploid chromosome complement was
      found in 54.6%; chromosomal abnormalities consisting of diploid sets were
      identified in 16.7% and aneuploidy was observed in 26%. Premature condensation of
      sperm chromosomes of the GI-phase was observed in 22.9% oocytes. Male infertility
      was correlated with an increase in the rate of aneuploidy when compared with
      tubal infertility. The rate of chromosome abnormalities for the oocytes recovered
      from women who had no fertilized oocytes was significantly higher compared to
      those with at least one oocyte fertilized. CONCLUSION: A high frequency of
      chromosome abnormalities in unfertilized oocytes suggests that natural selection
      against chromosome abnormalities may occur even prior to fertilization.

PMID- 7633165
TI  - Successful in vitro fertilization and pregnancy by micromanipulation with
      epididymal sperm.
AB  - PURPOSE: To examine the effectiveness of micromanipulation on the treatment of
      the patients with obstructive azoospermia, subzonal insemination or partial zona
      dissection was performed using epididymal sperm of the 23 patients, and the in
      vitro fertilization and embryo transfer (IVF-ET) outcomes were analyzed. RESULTS:
      Fertilized oocytes were obtained in 11 cycles of the 25 treated cycles, and six
      pregnancies were established by the subsequent ET. Through the analysis of 13
      cycles in which both the micromanipulation and usual IVF insemination were
      performed, the fertilization rate per oocyte with the micromanipulation [25%
      (28/113)] was significantly higher than that with the usual insemination method
      [4% (4/102)]. The micromanipulation was most useful for the treatment of the
      patients with congenital absence of the vas deferens. Moreover, there was no need
      to aspirate a large volume of the epididymal fluid, but it was essential to
      prepare more than 10 mature oocytes retrieved. CONCLUSIONS: These results
      indicate that micromanipulation with epididymal sperm is an effective treatment
      for obstructive azoospermia, and careful preparations of sperm and well
      controlled ovarian hyperstimulation are necessary for successful IVF-ET.

PMID- 7633166
TI  - Perinatal outcome of triplet pregnancies following assisted reproduction.
AB  - PURPOSE: This collaborative work was undertaken to assess perinatal outcome of in
      vivo conceived triplets to those following in vitro fertilization and assisted
      reproductive technologies (ART). METHODS: 151 triplets were examined; 56
      delivered following ART, 55 following ovulation induction by gonadotropins (GN),
      27 following clomiphene citrate (CC), and 13 conceived spontaneously. RESULTS:
      Mean gestational length of triplets following ART (33.2 wks) was not different
      from those conceived following GN (33.4 wks) or CC (34.2 wks), but was
      significantly shorter compared to triplets following spontaneous conception (35.3
      wks). Mean fetal birthweight following ART (1743 g) did not differ significantly
      from that following GN (1683 g) or CC (1863 g) but was significantly lower
      compared to those delivered after spontaneous conception (1963 g). Although no
      difference was found in the incidence of low birthweight infants between the
      groups studied, the incidence of very low birthweight newborns (<1500 g)
      following ART or GN was significantly higher than following spontaneous
      conceptions (30.6%, 30.3% vs 10.3%). Differences in perinatal mortality were not
      significantly different between the groups examined (77.9, 60.6, 111.0, 25.6/1000
      for ART, GN, CC, and spontaneous conceptions respectively). CONCLUSION: In
      conclusion, a similar perinatal outcome was shown for triplets conceived
      following ART and those following ovulation induction by GN, suggesting that the
      in vitro conditions as such were not the main contributing factor influencing the
      clinical outcome but rather the GN treatment. Triplets conceived spontaneously
      have a better outcome compared to those following ovulation induction or ART in
      terms of gestational length and birthweight.

PMID- 7633167
TI  - Characterization and prediction of IVF cycles generating "slow-cleaving" embryos.
AB  - PURPOSE: To characterize and predict cycles generating open quote slow-cleaving
      closed quote embryos in in vitro fertilization, 86 cycles were retrospectively
      divided into two groups (open quote slow, closed quote n=41, and open quote fast,
      closed quote n=45) according to whether the number of blastomeres per embryo on
      day 3 was < or = or > than the mean of the distribution, respectively. RESULTS:
      Cycles generating open quote slow-cleaving closed quote embryos were treated with
      luteinizing hormone-releasing hormone agonist before ovarian stimulation for a
      shorter period (12.1 +/- 0.5 versus 15.6 +/- 1.1 days; P < or = 0.01) and had
      higher immaturity grade of oocyte-corona-cumulus complexes which resulted in
      embryos (1.6 +/- 0.1 vs 1.3 +/- 0.1; P < or = 0.05) when compared to cycles
      producing "fast-cleaving" embryos. Both variables entered in a logistic
      regression model applied in order to predict the probability of a cycle
      generating "slow-cleaving" embryos (goodness-of-fit chi-square = 180.0, degrees
      of freedom (df) = 80, P = 0.4786). This model predicted correctly 86.7% (13 of
      15) of cycles generating "slow-cleaving" embryos and 83.3% (10 of 12) of cycles
      producing "fast-cleaving" embryos when the estimated probability of a cycle
      producing "slow-cleaving embryos" was > or = 0.7 or < or = 0.3, respectively.
      CONCLUSION: Shorter treatment with hormone-releasing hormone agonist before
      ovarian stimulation and higher immaturity grade of oocyte- corona-cumulus
      complexes which result in embryos are predictive characteristics of in vitro
      fertilization cycles generating "slow-cleaving" embryos.

PMID- 7633168
TI  - Induced acrosome reactions as fertility predictor.
AB  - PURPOSE: This study was conducted to determine the fertility predictive value of
      acrosome reaction rates and indices (induced minus control) of human spermatozoa.
      By comparison these outcomes with in vitro fertilization success. The effect of
      oocyte-cumulus complex exposure on the induction of the acrosome reaction was
      also analyzed. Patients attending our assisted reproduction unit for infertility
      treatment were included in the study. Acrosome reactions were determined on
      ethanol-permeabilized smears using FITC-conjugated Pisum sativum agglutinin. The
      acrosome reaction inducing agent used was calcium ionophore A23187 (10
      microM/ml). RESULTS: Poor correlations were found between all the acrosome
      reaction rates and indices and in vitro fertilization. The presence of oocyte
      cumulus complexes had no effect on the spontaneous acrosome reactions, but had a
      significant effect on the inducibility of the acrosome reaction. Exposure to
      oocyte-cumulus complexes resulted in the mean percentage sperm induced to be 7.8%
      (SE = 3.1%) higher compared to the control samples. CONCLUSIONS: Acrosome
      reaction rates and indices were therefore found to have no significant value in
      the prediction of male fertility and/or in vitro fertilization success. This
      study did, however, show that exposure to oocyte-cumulus complexes significantly
      increases the inducible sperm population.

PMID- 7633169
TI  - Selection of ovarian stimulation protocol is related to IVF treatment outcome in
      women 35 years of age and older.
AB  - PURPOSE: The aim of this study was to assess if the woman's age influenced IVF
      treatment outcome when a long GnRHa-hMG or a CC-hMG ovarian stimulation protocol
      was used. Two hundred women were included in the study, 100 women under the age
      of 35 and 100 women 35 years of age and older (mean 31.8 years and 36.7 years
      respectively). In the younger group as well as in the older group 50 women were
      stimulated according to a GnRHa-hMG protocol and 50 women received a CC-hMG
      regimen. RESULTS: Significant differences between stimulation protocols were
      found in the older group for the mean numbers of oocytes recovered (4.7 vs 3.0),
      preembryos obtained (3.2 vs 2.0) and replaced (2.3 vs 1.7), as well as pregnancy
      (30% vs 10%) and delivery (24% vs 4%) rates per replacement. CONCLUSION: It is
      concluded that women over 35 years of age seem to have a more favorable outcome
      of IVF treatment when using a long GnRHa-hMG protocol compared with CC-hMG, while
      this difference was not as obvious and lacking statistical significance under the
      age of 35.

PMID- 7633170
TI  - Study of the optimum time for human chorionic gonadotropin-ovum pickup interval
      in in vitro fertilization.
AB  - OBJECTIVE: To study the optimum time for ovum pickup after human chorionic
      gonadotropin (hCG) injection in in vitro fertilization. DESIGN: Prospective
      randomized study. SETTING: The Egyptian IVF-ET center. PATIENTS: Ninety couples
      with male factor infertility enrolled for intracytoplasmic sperm injection,
      divided into three groups. Ovum pickup was performed at 35 hr (group A), 36 hr
      (group B), and 37 hr (group C) after hCG injection. RESULTS: Number of metaphase
      II oocytes was significantly higher in group B compared to group A. There was no
      significant difference between group B and C. Fertilization rate was equal in all
      groups. The number of fertilized oocytes was significantly higher in group B as
      compared to group A, and there was no significant difference between groups B and
      C. CONCLUSION: Oocyte maturity in gonadotropin releasing hormone analogue
      agonist/human menopausal gonadotropin stimulated cycles is attained 36 hr after
      hCG injection. Oocyte retrieval should not be performed before 36 hr, and there
      is no risk of spontaneous ovulation between 36 and 37 hr.

PMID- 7633172
TI  - Serum C-reactive protein measurement in the detection of intercurrent infection
      in patients with sarcoidosis.
AB  - Patients with active sarcoidosis show minor or no elevation of serum C-reactive
      protein. During the research of the significance of measurement of this acute
      reactant in patients with active sarcoidosis, we noticed that during the
      intercurrent infection the levels of CRP rise significantly. This report shows
      that this observation is not an accidental event, but a rule. With this purpose
      in mind, we compared the values of serum CRP in 9 patients with active
      sarcoidosis during intercurrent infection and 17 with active sarcoidosis only.
      The difference was statistically significant; high levels were found in the sera
      of patients with intercurrent infection. Therefore, we consider this simple test
      a helpful means in the diagnosis of intercurrent infection in patients with
      active sarcoidosis.

PMID- 7633171
TI  - Developmental blockage of mouse embryos caused by fatty acids.
AB  - PURPOSE: It has been shown that lipid peroxides derived from polyunsaturated
      fatty acids (PUFAs) inhibit the proliferation of various cells. In the meantime,
      it has been suggested that oxidative stress is closely related to the
      developmental blockage of mammalian embryos cultured in vitro. In this study, we
      investigated the effects by various fatty acids on mouse embryo development in
      vitro, and the reversal of these effects by various antioxidants such as
      superoxide dismutase, ascorbic acid, alpha-tocopherol, uric acid, and
      ethylenediaminetetraacetic acid. METHODS: Pronuclear and two-cell stage mouse
      (ICR) embryos were cultured in Biggers-Whitten-Whittingham medium with 0.3%
      bovine serum albumin alone or complexed with one of the following fatty acids:
      palmitic, stearic, oleic, linoleic, linolenic, or arachidonic acid. We also
      measured the fluorescence emission of embryos in media containing various fatty
      acids in order to investigate the involvement of H2O2 or lipid peroxidation in
      embryo development. RESULTS: Palmitic acid and PUFAs including linoleic acid
      inhibited the embryo development. The inhibitory effect of PUFAs was attenuated
      by adding antioxidants into the media, while the inhibitory effect of palmitic
      acid was not. Both pronuclear and two-cell stage embryos with PUFAs showed
      markedly more intensive emissions than those under other conditions. CONCLUSIONS:
      These results suggest that lipid radicals can easily be generated in early stage
      embryos and that blastomeres are among the cells vulnerable to the damage by
      lipid peroxidation.

PMID- 7633173
TI  - Effect of neuroleptanaesthesia on VA/Q distribution and pulmonary shunt.
AB  - The authors studied changes in the ventilation-perfusion ratio and pulmonary
      shunt in the course of pulmonary surgery in relation to their presurgery values.
      The study was conducted at the Jordanovac University Department for Thoracal
      Surgery in Zagreb, examining 35 patients in whom, owing to pulmonary carcinoma,
      thoracotomy and pulmonary resection were performed. Relevant data were obtained
      concerning hypoxemia, its incidence, and its intensity in the patients examined.
      The results obtained have shown that in the presurgery period all the patients
      had an elevation of pulmonary shunt and an increased ratio of ventilation and
      blood flow, leading to mild hypoxemia. During the operation, the fall of the
      pulmonary shunt amounted to 8%; it was smaller after the ligature (bronchi,
      artery, and vein of the respective lung or its part) than at the end of the
      surgery (P < 0.001), whereas the ventilation-perfusion ratio fell more markedly
      after ligature (P < 0.001) than at the end of the operation. The authors conclude
      that, by knowing the ventilation-perfusion ratio and pulmonary shunt in the
      presurgical period, it is not possible to predict the changes of these parameters
      in the course of surgery. This is of special importance, because hypoxemia,
      occurring as a result of changes in the ventilation-perfusion ratio and pulmonary
      shunt, seriously endangers the patient's fate during surgery.

PMID- 7633174
TI  - Biomechanical features of axial injuries to the lower limbs and to the pelvic
      ring by motor car collisions.
AB  - By frontal car collision, passengers are exposed, commonly, by dynamic
      deceleration force, applied to the lower limb and acting in the direction of the
      femoral shaft axis. This force could be transmitted from the foot, or from the
      knee to the hip joint, resulting in typical fractures of the femoral shaft, upper
      part of the femur as of the acetabulum. The authors have described radiological
      feature and three dimensional definition of these fractures as well as their
      ergonomic characteristics. The purpose of this study was to explain biomechanical
      etiology of acetabular and proximal fractures of the femur. This analysis may be
      useful in prevention of these fractures.

PMID- 7633175
TI  - Institutional paranoia.
AB  - Taken separately, the concepts of institution and paranoia have no bearing on
      this work. They acquire their full new meaning as "institutional paranoia" only
      when they are taken together. Institutional paranoia is not a mental illness in
      the ordinary sense. It is a state, a condition, which exists in all associations
      and communities which have the same goal and concurrent intentions. The author's
      analysis of the problem is based on observation and monitoring of circumstances,
      discussions and content analysis, as well as on the use of questionnaires in
      several health institutions over a long period of time. He focuses his attention
      primarily on health, political, and economic institutions. The results of
      observation and analysis point to some interesting phenomena which require
      further study, regardless of their positive or negative outcome. With additional
      interventions, the content and dynamics of this process in institutions can
      contribute to the gradual diminishing of institutional paranoia, and sometimes
      its complete disappearance over a long time.

PMID- 7633176
TI  - Laryngeal war injuries.
AB  - During the war in Croatia in the region of Brodska Posavina at the Medical Center
      in Slavonski Brod, 7,043 wounded were treated. The Otolaryngology and Oral
      Surgery Service treated 728 wounded, of whom 20 had laryngeal injuries. Most of
      the injuries were caused by shrapnel from shells, mines, and hand grenades.
      Nineteen wounded had associated injuries of the neck, head, and the neck and/or
      other parts of the body. The authors performed in 8 surgical explorations and
      immediate reconstruction with the median layer of the deep cervical fascia
      (MLDCF). Upon termination of the treatment, the nineteen wounded had good
      respiration without signs of stenosis of the larynx. Twelve had good phonation,
      five satisfactory phonation, and two bad. None had swallowing difficulties. Among
      the eight wounded on whom the reconstruction of the larynx was done with cervical
      fascia, four had very good phonation, three satisfactory, and the eight died on
      the sixth postoperative day because of associated injuries to the cervical spine.
      The cervical fascia proved itself to be a suitable material in the immediate
      reconstruction of exogenous war injuries of the larynx.

PMID- 7633177
TI  - Plasmapheresis and hemodialysis in the treatment of acute renal failure in
      multiple myeloma.
AB  - Two patients with multiple myeloma (IgA-kappa and IgG-lambda) and severe acute
      renal failure were treated by combined plasmapheresis and hemodialysis. In both
      patients renal function was restored to normal. The pathogenetic role of M
      proteins and the possible mechanisms responsible for renal damage were discussed.
      While the addition of plasmapheresis has not been shown to extend survival, a
      reduction in the need for long-term dialysis appears to result from this
      intervention. It is concluded that the removal of M-proteins by plasmapheresis
      may be of therapeutic value in multiple myeloma patients.

PMID- 7633178
TI  - The effect of intravenous nitroglycerin therapy on infarct size in patients with
      acute myocardial infarction.
AB  - The authors investigated the influence of glyceryl-trinitrate (NTG) given
      intravenously to the reduction of infarction size in 95 patients (71 men and 24
      women) aged 36 to 75, with acute myocardial infarction (AIM) admitted to the
      Intensive Care Unit within six hours of the onset of pain. Infarction mass was
      calculated by mathematical model from the serial changes of CK and CK MB serum
      activities during 72 hours and expressed in CK and CK MB gEq. CK and CK MB were
      determined every four hours. The patients were divided into four groups according
      to the therapy they were receiving: I--NTG i.v. (n = 29); II SK + NTG i.v. (n =
      29); III SK i.v. (n = 17) and IV ISDN per os (n = 20). Each group was divided
      into subgroups regarding the time interval from the onset of pain to the
      beginning of the therapy (within three hours and after three hours). Application
      of NTG i.v. in the early phase of AIM, 0-3 hours from the onset of pain, led to
      the significant reduction of infarction mass CK gEq and CK MB gEq (0-3 hours;
      middle rank = 11.35; 3-6 hours: middle rank = 17.7) (P < 0.05) and 0-3 hours:
      middle rank = 10.31; 3-6 hours: middle rank = 18.81 (P < 0.01). It was
      established that the "timing" factor was very important in the preservation of
      myocardial mass in AIM. It affirms the efficacy of NTG i.v., i.e., its direct
      effects on the coronary arteries and systemic effects that cause salvation of the
      myocardium. The influence of NTG iv to myocardial infarction size CK gEq did not
      depend on ECG localization. But it influenced the ECG localization when the
      infarction size was calculated from CK MB isoenzyme and expressed in CK MB gEq.
      Infarction mass CK MB gEq was statistically significantly smaller in the inferior
      than in the anterior localization (P < 0.05).

PMID- 7633179
TI  - Neuromuscular disorders: gene location.

PMID- 7633180
TI  - Mitochondrial encephalomyopathies: gene mutation.

PMID- 7633181
TI  - Muscle imaging in health and disease.
AB  - Muscle imaging has been used largely as an adjunct in the assessment of patients
      with muscle disease and has been reported in descriptive terms only. Developments
      in computer-based image analysis techniques applied to muscle have enabled the
      quantification of muscle images using ultrasonography, computed tomography and
      magnetic resonance techniques. In conjunction with physiological measurements of
      muscle force, accurate determinations of muscle section area have allowed the
      determination of force per unit of cross-sectional area. This important
      measurement is essential if therapeutic approaches in muscle disease are to be
      adequately assessed. In this review the uses and merits of different imaging
      techniques are described with reference to new developments in quantitative
      analysis of muscle images and the possible utilisation of these techniques in
      neuromuscular disease is discussed.

PMID- 7633182
TI  - Motor activity patterns in rat soleus muscle after neonatal partial denervation.
AB  - In normal rats the development of organized patterns of hind limb movements takes
      place during the first three weeks of life. After removal of a part of the rat
      soleus muscle's innervation in 5-day-old animals, the remaining motoneurones
      occupy a large peripheral field. The possibility that the development of the
      normal activity patterns of these motor units may be altered was studied. The EMG
      activity of the soleus muscles partially denervated at five days was compared to
      that of the contralateral unoperated muscles during spontaneous locomotion and
      induced reflex activity in animals at various ages. Like a normal soleus the
      partially denervated soleus developed with age a tonic activity pattern but the
      aggregate activity recorded from the partially denervated soleus was less than
      that in the control muscle. However, the amount of activity per motor unit was
      higher in the operated than in the control muscles, since these had only one
      third to half of their normal complement of motor units. During locomotion both
      soleus muscles were activated like typical ankle extensors during the stance
      phase of the step cycle, but the burst duration of the operated muscle was
      significantly shorter. We conclude that partial denervation shortly after birth
      leads to an overall increase in activity of the remaining soleus motor units but
      does not drastically alter their temporal pattern of use during locomotion.

PMID- 7633183
TI  - TTR exon scanning in peripheral neuropathies.
AB  - Transthyretin (TTR) is a plasma protein in which most of the coding region is
      constituted of three exons, each one of approximately 200 bp. Several TTR
      variants have been reported in association with familial amyloid polyneuropathy
      (FAP) and the characterization of the mutations is crucial for understanding the
      process of amyloidogenesis. In order to simplify mutation screening and DNA
      sequencing studies, a method of exon scanning was developed employing duplex
      amplification of exon 2/3 and individual amplification of exon 4 followed by
      single strand conformation polymorphism analysis (SSCPs) on acrylamide gels and
      silver staining. In this work, 22 different known TTR mutations were
      discriminated and studies on 210 samples from patients with peripheral
      neuropathies detected one polymorphic mutation (TTR Ser 6), TTR Asn 90, found
      previously in the normal Portuguese and German populations, and three other
      mutations, one of them TTR Ala 60.

PMID- 7633184
TI  - Phospholipase A2 activity in dystrophinopathies.
AB  - Phospholipase A2 activity in human muscle with or without dystrophin abnormality
      was studied. The results showed an increased phospholipase A2 activity in
      Duchenne muscular dystrophy (DMD) patients (1160 +/- 160, P < 0.01) compared to
      controls (< 200 U mg-1). DMD fetal muscle showed normal levels, but levels then
      increased dramatically postnatally. Highest levels were found at 5 yr of age (10
      times normal) and then declined to 1.5-2 times normal by age 10. Steroid
      treatment did not change the phospholipase A2 levels significantly. In patients
      with abnormal dystrophin, i.e. Becker muscular dystrophy, phospholipase A2
      activity was increased in the age group 3-15 (920 +/- 230 U mg-1, P < 0.01),
      while older patients (17-49) showed a non-significant (220 +/- 60 U mg-1)
      increase. The lack of phospholipase A2 activation in fetuses with DMD, indicates
      that activation is not a direct consequence of dystrophin deficiency.
      Phospholipase A2 activity has been shown to be connected to the formation of
      several inflammatory mediators such as prostaglandins, leukotriens, platelet
      activating factor and lysophospholipids. Phospholipase A2 activation may
      therefore play an important role in the development of inflammation and necrosis,
      with subsequent fibrosis and massive loss of muscle function, which develops in
      Duchenne and Becker muscular dystrophy.

PMID- 7633185
TI  - DNA rearrangements in Japanese facioscapulohumeral muscular dystrophy patients:
      clinical correlations.
AB  - Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant muscular
      disorder in which the disease locus has been mapped to chromosome 4q35-qter. In
      most patients, the DNA rearrangements associated with FSHD have been found in the
      EcoRI fragment detected by the p13E-11 probe, and deletions of the 3.2 kb repeat
      units within the fragment are thought to cause the disease. To examine FSHD
      associated DNA rearrangements in the Japanese population, we performed Southern
      blot analysis of the genomic DNA, using the p13E-11 and pFR-1 probes, in 158
      Japanese individuals, including 38 FSHD patients from 19 families. We found that
      all but one (a possible affected recombinant) of the Japanese FSHD patients
      (97.4%) had specific smaller (< 28 kb) EcoRI fragments which cosegregated with
      the disease; this included four patients who had severe inflammatory changes in
      the muscle and eight patients with de novo DNA rearrangements. We found no FSHD
      patient who had a fragment larger than 28 kb. By contrast, only two of 35
      Japanese controls (5.7%) had EcoRI fragments smaller than 28 kb. Our patients
      showed anticipation, i.e. decreased size of the EcoRI fragment in parallel with
      earlier onset of the disease (r = 0.531, P = 0.003, with younger age at onset in
      children (17.8 +/- 7.0) than their affected parents (31.5 +/- 14.8) (P = 0.019).
      However, since each family had a specific small EcoRI fragment associated with
      the disease, the differing clinical severity within a family cannot be explained
      by the size of the fragment alone.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7633186
TI  - Muscle X-inactivation patterns and dystrophin expression in Duchenne muscular
      dystrophy carriers.
AB  - Muscle pathology, dystrophin expression and X-inactivation patterns were studied
      in the muscle of five asymptomatic females heterozygous for deletions in the
      dystrophin gene (non-manifesting carriers) and five symptomatic carriers
      (manifesting carriers). Muscle from the non-manifesting carriers showed an
      increase in the population of centrally nucleated fibres (9.0 +/- 2.8%; controls,
      1.4 +/- 0.3%), frequent fibers with abnormally interrupted dystrophin staining
      (38 +/- 5%), and, in sections from three individuals, small numbers of dystrophin
      negative fibers (1-4%). The amount of dystrophin measured by immunoblotting was
      reduced to 64 +/- 5% (P < 0.001 n = 5) of normal. The pattern of X-inactivation
      in muscle DNA was non-biased (50: 50-60: 40) in all cases. In the manifesting
      carriers both highly biased (90: 10) and non-biased patterns of X-inactivation
      were found, but no consistent relationship was apparent between the patterns of X
      inactivation and the proportions of dystrophin-negative fibers. We conclude from
      studies of the non-manifesting carriers that the proportion of residual
      dystrophin is similar to the relative activation in muscle of the X-chromosome
      carrying the wild-type allele. Extreme bias of X-inactivation can be associated
      with early clinical symptoms and severe pathology. However, as non-manifesting
      and some manifesting adult carriers had identical patterns of X-inactivation,
      abnormalities in the distribution of dystrophin, as well as overall levels of
      expression, may be important for the development of myopathic pathology.

PMID- 7633187
TI  - Muscle-eye-brain disease and Fukuyama type congenital muscular dystrophy are not
      allelic.
AB  - Muscle-Eye-Brain disease (MEB) and Fukuyama type congenital muscular dystrophy
      (FCMD) are clinically similar autosomal recessive diseases, characterized by
      congenital muscular dystrophy and severe mental retardation, raising the
      possibility that they might be caused by mutations of the same gene. Recently
      FCMD was localized to chromosome 9q31-33 by linkage. We performed a linkage study
      in seven Finnish MEB families with 12 affected patients using markers D9S53,
      D9S58, D9S59 and HXB. The MEB phenotype was not linked to any of the markers. A
      multipoint linkage analysis excluded the entire region harboring FCMD. We thus
      conclude that MEB and FCMD are not allelic.

PMID- 7633188
TI  - Familial concordance of brain magnetic resonance imaging changes in congenital
      muscular dystrophy.
AB  - Cerebral white matter changes have been described in a significant number of
      individual patients with "pure" congenital muscular dystrophy without clinical
      evidence of central nervous system involvement. The cause for the imaging changes
      is unknown but it is possible that they are the result of abnormal expression in
      the brain of the gene also responsible for the muscular dystrophy. In this study
      magnetic resonance imaging of the brain was performed on seven sibling pairs with
      congenital muscular dystrophy and normal intelligence to establish whether
      imaging changes are consistent within families. Diagnosis of congenital muscular
      dystrophy was based on clinical and muscle biopsy findings. Children from two
      families had normal scans; the remaining five sibling pairs showed white matter
      changes and within each family the changes were virtually identical in severity
      and distribution. Our data indicate that the central nervous system changes are
      consistent within individual families, suggesting that they probably relate to
      the mutation in the congenital muscular dystrophy genes involved in the
      respective families.

PMID- 7633189
TI  - Low-dose prednisolone treatment in Duchenne and Becker muscular dystrophy.
AB  - Forty-one boys, aged 4.0-19.4 yr, with Duchenne or Becker muscular dystrophy,
      took part in a 12-month randomized, double-blind cross-over trial in which the
      patients received 0.35 mg kg-1 day-1 prednisolone for six months and placebo for
      six months. One patient stopped the treatment because of excessive weight gain.
      The boys were assessed every third month with a comprehensive test battery of
      muscle force and function. The results support earlier reports that prednisolone
      treatment can either improve muscle force and function or diminish the
      deterioration of muscle function in both Becker and Duchenne muscular dystrophy.

PMID- 7633190
TI  - Peter Emil Becker--a short biography on the occasion of his 85th birthday.

PMID- 7633191
TI  - Human immunodeficiency virus infection in Taiwan, 1984 to 1994.
AB  - From 1984 to September 1994, a total of 9,099,734 serum samples from six
      population groups were tested for the antibody to human immunodeficiency virus
      type 1 (HIV). Mandatory testing was carried out for blood donors, military
      recruits, immigrants and prisoners; other population groups were tested
      anonymously with consent. A total of 695 samples were seropositive and, of these
      HIV carriers, 142 developed acquired immunodeficiency syndrome (AIDS). Although
      the prevalence of HIV infection and AIDS has remained low, there has been a rapid
      increase since 1991. Of the 142 AIDS cases, 68 were in homosexuals/bisexuals, 6
      were in hemophiliacs, 7 were in prisoners/intravenous drug users, 49 were in
      heterosexuals and for 12 cases, the risk factors were unknown. Before 1987, 69
      (90.8%) of the 76 HIV-infected persons were homosexuals or hemophiliacs.
      Thereafter, the risk groups diversified, with the main group shifting from
      hemophiliacs to intravenous drug users, and the number of heterosexuals
      surpassing that of homosexuals. Among the 142 cases of AIDS, 135 were males and
      only 7 were females. Despite the short period of follow-up, 114 have died
      (including 3 suicides).

PMID- 7633192
TI  - Diagnosis of coronary artery disease using dipyridamole thallium-201 imaging.
AB  - Dipyridamole thallium-201 imaging, using single-photon emission computed
      tomography, was evaluated for its safety and diagnostic efficacy in 109 patients
      with angiographically documented coronary artery disease and 35 normal subjects.
      The most common side effects after the intravenous administration of dipyridamole
      thallium-201 (0.56 mg/kg) included chest pain in 41 patients, dizziness in 20
      patients, headache in 16 patients, and ST segment depression > or = 1 mm in 15
      patients. Aminophylline was required to reverse the side-effects in 46 patients,
      and 45 of the 46 patients experienced complete relief of symptoms. Of the 109
      patients with coronary artery disease, 104 had abnormal dipyridamole thallium
      images. The per patient sensitivity was 95%. Of the 35 normal subjects, 27 had
      normal thallium images. The per patient specificity was 77%. The sensitivity and
      specificity for the individual vessels were 84% and 87% for the left anterior
      descending artery, 67% and 97% for the left circumflex artery, and 89% and 85%
      for the right coronary artery, respectively. Dipyridamole thallium-201 imaging is
      a relatively safe noninvasive method and is an effective alternative to exercise
      thallium-201 scintigraphy for the diagnosis of coronary artery disease.

PMID- 7633193
TI  - Effect of pentoxifylline on intraperitoneal adhesions after intestinal resection
      in rats.
AB  - Pentoxifylline, an analogue of the methylxanthine theobromine, inhibits
      glycosaminoglycan and collagen synthesis by dermal fibroblasts in vitro and also
      inhibits the proliferation of dermal fibroblasts. It may have the same effect on
      fibroblasts derived from postoperative adhesion bands, thus preventing
      postoperative adhesion formation. An animal model was developed to evaluate the
      effect of pentoxifylline. Twenty-four male Wistar rats were divided into four
      groups, and all underwent laparotomy with a 15 cm intestinal resection and
      reanastomosis. The intestinal serosa was scratched to induce adhesion formation.
      No medication was given in group 1 rats, group 2 rats received 6 mL normal saline
      by intraoperative peritoneal irrigation, group 3 rats received 6 mL
      pentoxifylline solution (1 mg/mL) by intraperitoneal irrigation and group 4 rats
      received both 6 mL intraoperative pentoxifylline solution (1 mg/mL) irrigation
      and 50 mg/kg pentoxifylline by intramuscular injection, twice a day for 14 days.
      All rats were sacrificed 2 weeks later. The numbers of fibrous bands at and away
      from the anastomotic site were recorded and scored. The score for each rat was
      calculated as the sum of the scores for each band. The strength and the extent of
      the fibrous bands were also measured and compared. The scores of adhesion bands
      at the anastomotic site were significantly reduced in group 3 and group 4 rats
      when compared with group 1 rats. However, there were no significant differences
      among the 4 groups in the extent and strength of adhesions at sites other than
      the anastomosis site.

PMID- 7633194
TI  - Measurement of human chorionic gonadotropin by carboxyl terminal peptide assay in
      patients with cervical neoplasm.
AB  - The aim of this study was to investigate whether human chorionic gonadotropin
      (hCG) is produced by preinvasive cancer and the early stages of invasive cancer.
      One hundred and fifty-two patients with either various grades of preinvasive
      cervical carcinoma or microinvasive carcinoma, and 46 normal women used as
      controls, were enrolled in this study. A carboxyl terminal peptide beta-hCG (CTP
      beta-hCG) assay with a sensitivity of 0.2 mIU/mL was used to measure serum
      levels. The results showed that the serum beta-hCG levels among normal control,
      preinvasive carcinoma and microinvasive carcinoma patients were not statistically
      different. Among the factors tested, including the interval since the last
      menstrual period, age, menopausal status, contraception method and diagnosis,
      serum hCG levels only correlated with the first factor. Preinvasive cervical
      carcinoma and microinvasive carcinoma did not result in significantly increased
      hCG secretion. At present, the CTP-beta-hCG assay is of limited value in the
      diagnosis of these diseases.

PMID- 7633195
TI  - Fibronectin levels in normal pregnancy and preeclampsia.
AB  - Vascular endothelial damage is reported to be the prime cause of preeclampsia,
      and elevated levels of fibronectin have been found before clinical signs of
      preeclampsia were manifested. The total plasma fibronectin concentrations in 212
      blood samples from 173 normotensive healthy pregnant women at various gestational
      ages were measured. Fibronectin levels were also determined for 20 blood samples
      from 20 preeclamptic patients obtained at the time of clinical manifestation of
      preeclampsia. Blood samples from 46 non pregnant women of reproductive age were
      used as controls. The results showed that the total plasma fibronectin
      concentration during reproductive age was independent of age and the average
      level during pregnancy decreased with gestational age. Preeclamptic patients had
      a significantly elevated level of total fibronectin compared with healthy
      pregnant women. The total fibronectin concentration is a promising biochemical
      marker for preeclampsia, but a more specific endothelial method of measurement is
      needed before it is put to clinical use.

PMID- 7633196
TI  - Increased insulin-like growth factor-1 receptors in thyroid tissues of Graves'
      disease.
AB  - Insulin-like growth factor-1 (IGF-1) plays an important role in thyroid cell
      growth and human thyroid diseases. In order to investigate the involvement of IGF
      1 in abnormal thyroid growth in Graves' disease, 20 patients with Graves' disease
      were enrolled in this study. Thirty euthyroid subjects were used as normal
      controls for the radioimmunoassay study of circulating IGF-1. Seven normal
      thyroid tissue fragments from 3 patients with papillary carcinoma and 4 patients
      with benign thyroid nodule were used as controls in the radioligand binding
      assay. The concentration of serum IGF-1 in the diseased group was not
      significantly different from normal controls. In the radioligand study,
      competitive binding studies with thyroid membrane showed that [125I]IGF-1 was
      dose-dependently displaced by unlabeled IGF-1, and its potency was 630 times
      higher than insulin. The Scatchard plot of 6 saturation studies revealed similar
      Kd in the Graves' group and the control group. In contrast, there was a
      significantly higher specific binding ratio and higher binding capacity in the
      Graves' group than in the control group. These results suggest that higher IGF-1
      receptor numbers rather than higher circulating IGF-1 may be a contributing
      factor to goiter formation in Graves' disease.

PMID- 7633197
TI  - Ultrasonographic findings of papillary thyroid carcinoma and their relation to
      pathologic changes.
AB  - To elucidate the ultrasonographic findings in papillary thyroid carcinoma and
      their relation to pathologic changes, 47 patients on whom thyroid ultrasonography
      had been performed and whose thyroid tissues were pathologically proven to be
      papillary thyroid carcinoma were studied. The ultrasonographic findings were
      reviewed and correlated with the pathologic changes. Fifty-three out of 94
      thyroid lobes had papillary carcinoma. The ultrasonographic features of the
      affected thyroid lobes were hypoechoic in 46, isoechoic in 6 and hyperechoic in
      1. The ultrasonographic texture of all 53 lesions was heterogeneous. The margin
      was clear in 11 lesions and unclear in 42. Cystic degeneration was found in 15
      lesions. Discrete particles representative of microcalcifications were found in
      25 lesions. Halo signs were found in 7 lesions. Lymph node enlargement was
      detected in 4 cases. The sensitivity and specificity of each ultrasonic finding
      in predicting the respective pathologic feature were: unclear margin for tumor
      invasion, 84% and 31%; cystic degeneration for cysts, 42% and 79%; discrete
      particles for microcalcification, 50% and 52%; halo sign for total encapsulation,
      42% and 88%; and lymph node enlargement for lymph node metastasis, 18% and 100%,
      respectively. These data suggest that ultrasonographic findings in papillary
      carcinoma were usually hypoechoic and heterogeneous. An unclear margin in
      sonography is fairly sensitive for the prediction of tumor invasion.

PMID- 7633198
TI  - Effects of fluid retention on the measurement of body composition using
      bioelectric impedance.
AB  - Body composition measurements using bioelectrical impedance analysis (BIA) were
      performed on 50 uremic patients immediately before and after hemodialysis (HD)
      therapy, on 10 uremic patients under continuous ambulatory peritoneal dialysis
      (CAPD) therapy before and after the fluid was drained out of the peritoneal
      cavity and on 3 cirrhotic patients before and after abdominal paracentesis.
      Thirty-two pairs of measurements were performed on the CAPD patients and 3 pairs
      on the cirrhotic patients. Significant increases in both resistance and reactance
      were noted after HD. However, resistance and reactance before and after
      peritoneal fluid had been drained were not significantly different. In HD, body
      fluid loss as estimated by BIA (LBIA) was higher than that from the body weight
      method (LBW). The relationship between the two is described by the equation LBW =
      0.841LBIA + 0.588. The total body fat estimated before HD was significantly lower
      than after HD, and it was significantly higher when measured with peritoneal
      fluid retention than with fluid drained. Generalized edema caused an increase in
      resistance and reactance, while local peritoneal fluid retention did not cause
      any significant changes. When total body fluid is measured by the BIA method, it
      is often overestimated in the case of generalized edema and underestimated in
      case of peritoneal fluid retention. Therefore, total body fat is underestimated
      by BIA in generalized edema before HD and overestimated in peritoneal fluid
      retention.

PMID- 7633199
TI  - Defecographic evaluation of patients with defecation difficulties.
AB  - Defecographic studies were carried out in 36 females and 19 males with specific
      complaints of straining with defecation, incomplete rectal emptying and perineal
      descent. Of these, 91% had abnormal defecographic findings. Abnormalities were
      more common in females than in males. The female patients mean anorectal angles
      were 111.3 degrees (resting), 102.2 degrees (squeezing) and 124.7 degrees
      (straining). Their mean anterior rectocele size was 1.8 cm and the mean
      difference between the pelvic floor and the anorectal junction at rest and during
      maximal straining, the mean Ds-R, was also 1.8 cm. Ninety-one percent of the
      females had anterior rectoceles, 33% had internal rectal intussusception, 25% had
      hypertonic puborectalis slings and 22% had a Ds-R > 3 cm. The mean anorectal
      angles of the males were 116.3 degrees (resting), 102.0 degrees (squeezing) and
      132.9 degrees (straining) and the mean Ds-R was 2.0 cm. Sixty-eight percent of
      the males had hypertonic puborectalis slings, 58% had internal rectal
      intussusception, and 42% had a Ds-R > 3 cm. All patients with hypertonic
      puborectalis slings had smaller, more acute straining angles. Males with abnormal
      perineal descent had a greater Ds-R than patients without perineal descent.

PMID- 7633200
TI  - Mixed cellular population in primary and metastatic periampullary adenocarcinoma
      of the duodenum: report of a case.
AB  - There are numerous reports on the mixed cellular population of primary tumors,
      especially in the gastrointestinal tract. However, reports of mixed cellular
      population in metastatic foci are rare. This is a report of a case of
      periampullary papillary adenocarcinoma of the duodenum with 4 types of cellular
      population. Metastases to the regional lymph nodes also contained 4 different
      cell types. The histogenesis of the mixed cellular population in the primary
      tumor and theories proposed to explain the pathophysiologic mechanisms of mixed
      cellular population in the metastatic foci are discussed.

PMID- 7633201
TI  - Hormonal studies and Doppler flow imaging of ovarian lipoid cell tumors: report
      of two cases.
AB  - Ovarian lipoid cell tumors are very rare. We report two cases with abnormal
      menstruation, hirsutism, clitoromegaly and marked elevations of serum
      testosterone. Sonography revealed unilateral adnexal solid tumors. Flow velocity
      wave form study showed apparent flow within the tumor with the resistance index
      ranging from 0.42 to 0.49 in both cases. Unilateral oophorectomy and
      contralateral ovarian biopsy were performed. Frozen sections showed lipoid cell
      tumors without malignant change. During surgery, direct ovarian venipuncture
      showed a discrepancy in testosterone level in the bilateral ovaries of both
      patients and large ovarian-peripheral venous gradients in case 2. The
      testosterone concentration returned to normal postoperatively in both cases. Flow
      velocity wave form study and direct ovarian venipuncture are useful tools for
      evaluation of androgen-secreting tumors preoperatively and intraoperatively.

PMID- 7633202
TI  - Cytogenetic investigations in trisomy 21 with reciprocal 4/9 translocation:
      report of a case.
AB  - A 3-month-old male infant with Down's syndrome resulting from de novo trisomy 21
      had an additional reciprocal translocation between the long arms of chromosomes 4
      and 9: 47,XY,+21,rcp t(4;9)(q35;q22.3). Both C- and Ag-NOR bandings showed that
      the extra chromosome 21 was maternal in origin, but that the translocated
      chromosome 9 was from the father. To evaluate the nature of the translocation,
      fluorescence in situ hybridization (FISH) with whole chromosome painting probes
      (Coatasomes 4 & 9), followed by an enzymatic precipitation (HRP-DAB) assay was
      used. Whole chromosome FISH demonstrated the origin of the translocated region
      and clarified the karyotype. Enzymatic methods achieved the same result and were
      kept as a permanent record.

PMID- 7633203
TI  - Hemimegalencephaly treated by hemispherectomy: report of two cases.
AB  - Hemimegalencephaly is a rare congenital anomaly of the brain characterized by
      unilateral hypertrophy, usually with an abnormal gyri pattern and derangement of
      the cortical architecture. We report 2 patients with hemimegalencephaly who
      presented with early-onset seizures, hemiparesis and developmental delay. An
      electroencephalogram showed hemispheric continuous spikes and spike-and-waves in
      one patient and repetitive spike-and-waves in the other. Magnetic resonance
      imaging showed left hemimegalencephaly in both cases and in case 1 pachygyria and
      heterotopia. A functional hemispherectomy was done on case 1 at the age of 33
      months and on case 2 at 7 months due to difficulty in seizure control with
      antiepileptic drugs. The frequency of seizure dramatically decreased and there
      was an obvious improvement in neurologic development after surgical intervention.
      Pathology revealed disorganized lamination of the cortical layers with increased
      neuron size and bizarre-shaped neurons in both cases. Heterotopia of neurons and
      glia in the subarachnoid space was noted in case 1. Hemispherectomy should be
      performed as soon as possible when medical treatment fails to control seizures.

PMID- 7633204
TI  - Prenatal diagnosis of Dandy-Walker malformation: report of a case.
AB  - Dandy-Walker malformation is one of the major causes of congenital hydrocephalus.
      We report on a case that was diagnosed by sonography in a fetus at 34 weeks'
      gestation. The diagnosis was confirmed by postnatal computed tomographic (CT)
      brain scan and magnetic resonance imaging (MRI). The prenatal sonographic
      findings were a large posterior fossa in communication with the fourth ventricle,
      a small and splayed cerebellar hemisphere and marked degrees of ventriculomegaly.
      The postnatal CT scan images were similar to the prenatal sonography. The
      hypoplasia of the cerebellar vermis and the associated hypogenesis of the corpus
      callosum can only be clearly delineated by MRI. Dandy-Walker malformation is one
      form of the Dandy-Walker complex and cystic malformations of the posterior fossa.
      It should be differentiated from Dandy-Walker variant, or mega-cisterna magna,
      and arachnoid cyst. Dandy-Walker complex may be associated with chromosomal,
      intracranial and extracranial abnormalities. Early in utero detection is useful
      for detailed evaluation of associated anomalies. Obstetric management depends on
      gestational age, karyotype abnormality and associated intracranial and
      extracranial anomalies. In the present report, the infant presented no
      progressive ventriculomegaly and no surgery was required. The infant developed
      normally.

PMID- 7633205
TI  - Double-orifice mitral valve: report of two cases.
AB  - Two cases of double-orifice mitral valve are reported. The first case was
      associated with coarctation of the aorta and a large perimembranous ventricular
      septal defect, and the second case had an associated large patent ductus
      arteriosus. A bridge-type defect created two equal-sized openings in the mitral
      valve in case 1. In case 2, a small accessary opening was located in the
      posteromedial leaflet of the mitral valve. Double-orifice mitral valve is a rare
      anomaly associated with coarctation of the aorta, ventricular septal defect, and
      patent ductus arteriosus. The morphology of a double-orifice mitral valve can be
      clearly delineated by 2-D echocardiography.

PMID- 7633206
TI  - Intrathoracic migration of Kirschner wires.
AB  - Two cases of intrathoracic migration of Kirschner wires are reported. Two wires
      were used to fix a left clavicle fracture in case 1. Two months later, a chest
      film showed a broken wire migrating into the mediastinum. A chest computed
      tomogram revealed the Kirschner wire penetrating into the main pulmonary artery.
      The broken wire was removed through sternothoracotomy after a pericardiotomy. In
      case 2, repeated blood-tinged sputum was experienced 5 years and 6 months after
      Kirschner wire fixation of 2 left clavicle fractures. Chest film showed the
      migrated wire located in the right thorax. The wire was removed through right
      thoracotomy. In both cases, the foreign bodies were successfully removed and
      vascular and pulmonary repair were performed without morbidity.

PMID- 7633207
TI  - Portrait of a Virginia Henderson fellow: Rozella M. Schlotfeldt.

PMID- 7633208
TI  - Advancing scholarship and leadership. Interview by Judy A Beal and Hussein Tahan.

PMID- 7633209
TI  - Astronaut aids health research. Interview by Marilyn Rubin and Sarah Gueldner.

PMID- 7633210
TI  - Computer networks advance traditional nursing. Interview by Sharon Decker.

PMID- 7633211
TI  - Nurse guiding nurse, mentoring. Interview by Barbara Robinette.

PMID- 7633212
TI  - Folklore and nursing. An account of use in reminiscence groups.

PMID- 7633214
TI  - Profiles of nursing excellence. Fostering healthier nations. Interview by Pamela
      C Levi.

PMID- 7633213
TI  - Leadership externs: interactions, involvement, interpersonal rewards.

PMID- 7633215
TI  - Judith Longworth, RN, PhD, CS, FNP. Urban health care. Interview by Barbara
      Given.

PMID- 7633216
TI  - Breaking the barrier of not caring: urban nursing.

PMID- 7633217
TI  - Left ventricular hypertrophy.

PMID- 7633218
TI  - What's happening to nursing?

PMID- 7633219
TI  - Science and Technology Committee's report on genetics.

PMID- 7633220
TI  - CS gas injury to the eye.

PMID- 7633221
TI  - Hundreds die in US as temperatures reach 41 degrees C.

PMID- 7633222
TI  - BUPA limits intensive care.

PMID- 7633223
TI  - Britain is getting fatter, says government.

PMID- 7633225
TI  - Abortion in France still under attack.

PMID- 7633224
TI  - South African surgeon breaks transplant ban.

PMID- 7633226
TI  - British road traffic deaths fall but casualties rise.

PMID- 7633227
TI  - New ambulance targets could save 3000 lives a year.

PMID- 7633229
TI  - How the Eurocrats affect our health.

PMID- 7633228
TI  - Belgian doctor wins fight for training certificate.

PMID- 7633230
TI  - Risk factors for HIV infection in people attending clinics for sexually
      transmitted diseases in India.
AB  - OBJECTIVE: To investigate the risk factors for HIV infection in patients
      attending clinics for sexually transmitted diseases in India. DESIGN: Descriptive
      study of HIV serology, risk behaviour, and findings on physical examination.
      SUBJECTS: 2800 patients presenting to outpatient clinics between 13 May 1993 and
      15 July 1994. SETTING: Two clinics and the National AIDS Research Institute, in
      Pune, Maharashtra State, India. MAIN OUTCOME MEASURE: HIV status, presence of
      sexually transmitted diseases, and sexual behaviour. RESULTS: The overall
      proportion of patients infected with HIV was 23.4% (655/2800); 34% (184) of the
      women and 21% (459) of the men were positive for HIV infection. Of the 560 women
      screened, 338 (60%) had a reported history of sex working, of whom 153 (45%) were
      infected with HIV-1. The prevalence of HIV-1 infection in the 222 women who were
      not sex workers was 14%. The significant independent characteristics associated
      with HIV infection based on a logistic regression analysis included being a
      female sex worker, sexual contact with a sex worker, lack of formal education,
      receptive anal sex in the previous three months, lack of condom use in the
      previous three months, current or previous genital ulcer or genital discharge,
      and a positive result of a Venereal Disease Research Laboratory test.
      CONCLUSIONS: In India the prevalence of HIV infection is alarmingly high among
      female sex workers and men attending clinics for sexually transmitted diseases,
      particularly in those who had recently had contact with sex workers. A high
      prevalence of HIV infection was also found in monogamous, married women
      presenting to the clinics who denied any history of sex working. The HIV epidemic
      in India is primarily due to heterosexual transmission of HIV-1 and, as in other
      countries, HIV infection is associated with ulcerative and non-ulcerative
      sexually transmitted diseases.

PMID- 7633231
TI  - Complications with shunts in adults with spina bifida.
AB  - OBJECTIVE: To assess the incidence of malfunction of shunts in adults with spina
      bifida who have shunts to control hydrocephalus. DESIGN: A retrospective review
      of the medical notes and contact by questionnaire of adults with spina bifida to
      assess symptoms, function of shunts, frequency of operative procedures, and
      follow-up. SUBJECTS: 110 patients with shunts who attended Lord Mayor Treloar
      College for the physically disabled between 1978 and 1993. RESULTS: The average
      (range) number of revisions of shunts per person was 3.6 (0-28). Although 37
      patients underwent an emergency operation for revision in their first year of
      life, there was a continuing low incidence, increasing in the early teenage
      years, which persisted into the third decade. Intervals between emergency
      revisions varied: 202/320 occurred within one year of the last shunt operation,
      56 occurred after five years, 24 after 10 years, and 15 after 15 or more years.
      Fifteen patients had chronic intermittent headaches, of whom four died and three
      suffered severe morbidity. Thirteen died; three had raised intracranial pressure,
      and four died suddenly; these deaths were presumed to be related to their shunts.
      Up to the age of 16 there was 100% hospital follow up, but after that only 40% of
      young adults underwent review, including review of their shunt function.
      CONCLUSION: Shunts to control hydrocephalus may fail after many years without
      symptoms. This is difficult to diagnose and if missed may lead to chronic
      morbidity and death. As hospital follow up of this group is falling, both general
      practitioners and hospital doctors must be aware that a shunt may malfunction
      after prolonged quiescent periods.

PMID- 7633232
TI  - Emergency psychiatric services in England and Wales.

PMID- 7633234
TI  - Health promotion by encouraged use of stairs.

PMID- 7633233
TI  - Subarachnoid haemorrhage in first and second degree relatives of patients with
      subarachnoid haemorrhage.

PMID- 7633235
TI  - Combined clinical and virological surveillance of influenza in winters of 1992
      and 1993-4.

PMID- 7633236
TI  - Fulminant hepatic failure induced by lamotrigine.

PMID- 7633237
TI  - Water intoxication after low dose cyclophosphamide.

PMID- 7633238
TI  - Discontinuation of and changes in treatment after start of new courses of
      antihypertensive drugs: a study of a United Kingdom population.
AB  - OBJECTIVE: To evaluate the incidence of discontinuation of and changes in
      treatment after newly prescribed courses of antihypertensive drugs of the four
      primary therapeutic classes: beta blocker, calcium channel blocker, and
      angiotensin converting enzyme inhibitor. DESIGN: A retrospective analysis of
      patients on an automated database of 1.2 million patients was conducted on visits
      between 1 October 1992 and 30 September 1993. SETTING: General practices in the
      United Kingdom. SUBJECTS: 37,643 patients with hypertension receiving a relevant
      drug in the time period were identified. A new course of treatment in at least
      one of the four therapeutic classes, defined as a drug not prescribed in the
      previous four months, was observed in 10,222 patients aged > or = 40 years. MAIN
      OUTCOME MEASURES: Patients changing to other treatment or discontinuing after
      initiating a new course of treatment, defined as the absence of a refill
      prescription for the new drug or another in its category within a six month
      observation period. RESULTS: Changes in or discontinuation of treatment were
      frequently observed, and by month six continuation rates ranged between 40% to
      50% for all four classes of drugs. CONCLUSION: Low rates of continuation with a
      newly prescribed antihypertensive drug exist regardless of which drug is
      prescribed.

PMID- 7633239
TI  - Variations in medical attitudes to postoperative recovery period.

PMID- 7633240
TI  - Harmonisation of specialist training in Europe: is it a mirage?
AB  - For the past 18 years there has been a proliferation of European committees,
      boards, associations, colleges, and working groups set up to promote the
      harmonisation of specialist training in Europe. It has been taken as read that
      this objective is desirable. The fact that these bodies have achieved remarkably
      little is telling, and it is time to question their activity. There are good
      practical reasons behind the evolution of Europe's disparate training schemes,
      and the arguments for retaining diversity rather than continuing to strive for
      homogeneity are persuasive.

PMID- 7633241
TI  - Qualitative research. Introducing focus groups.
AB  - This paper introduces focus group methodology, gives advice on group composition,
      running the groups, and analysing the results. Focus groups have advantages for
      researchers in the field of health and medicine: they do not discriminate against
      people who cannot read or write and they can encourage participation from people
      reluctant to be interviewed on their own or who feel they have nothing to say.

PMID- 7633242
TI  - Has nursing lost its way? Dual perspective.

PMID- 7633243
TI  - Has nursing lost its way? Nursing and medicine: cooperation or conflict?

PMID- 7633244
TI  - Has nursing lost its way? Towards an ethos of interdisciplinary practice.

PMID- 7633245
TI  - Has nursing lost its way? Nursing: no regrets.

PMID- 7633246
TI  - With nurse practitioners, who needs house officers?
AB  - The boundaries between the work of doctors and that of nurses are changing, with
      nurses taking over important parts of junior hospital doctors' clinical work. In
      1993 an exploratory study was carried out to identify the professional,
      educational, and management issues that such developments raise. Interviews were
      carried out with a range of stakeholders in three innovatory posts in which
      nurses were doing much of the clinical work of house officers. A complex picture
      of perceived benefits and problems for patients, junior doctors, and nurses
      emerged. These seemed to be associated with (a) the extent to which the
      contribution of professional nursing was valued in the new role and (b) the
      amount of clinical discretion which the postholder was allowed, this depending on
      the type of preparatory education provided and the management of the post. The
      study points to the need for strategic issues--such as the development of
      appropriate education and the professional recognition of these new clinical
      roles--to be addressed at a national and regional level.

PMID- 7633247
TI  - Use of Read codes in development of a standard data set.
AB  - General practice has a wealth of data that could be used for purposes such as
      assessing health needs, planning, and audit. If this potential is to be realised
      appropriate data must be easily accessible and of high quality. This article
      describes the experience of an information project team in developing and coding
      a standard data set, with the aim of meeting the needs of commissioners, public
      health, and general practitioners. The Read coding classification seemed the
      logical choice for the standard data set because Read codes are the basis of a
      standard classification of general practice data. However, the coding structure
      has several weaknesses that were difficult to resolve, and the standard data set
      had to be changed to match available codes. This paper may prove helpful to
      similar project teams attempting to develop and use a standard data set.

PMID- 7633248
TI  - Use facilitated case discussions for significant event auditing.
AB  - An important type of review undertaken routinely in health care teams is analysis
      of individual cases. This informal process can be turned into a structured and
      effective form of audit by using an adaptation of the "critical incident"
      technique in facilitated case discussions. Participants are asked to recall
      personal situations that they feel represent either effective or ineffective
      practice. From such review of individual cases arise general standards to improve
      the quality of care. On the basis of a study of audit of deaths in general
      practice, we describe how to implement such a system, including forming and
      maintaining the discussion group, methodology, and guidelines for facilitators.
      Problems that may arise during the case discussions are outlined and their
      management discussed, including problems within the team and with the process of
      the discussions.

PMID- 7633249
TI  - A nurse's place is at the bedside.

PMID- 7633250
TI  - Open access echocardiography. General practitioners use echocardiography
      approximately.

PMID- 7633251
TI  - Open access echocardiography. General practitioners also use open access computed
      tomography wisely.

PMID- 7633252
TI  - Open access echocardiography. Hospital patients need open access
      echocardiography.

PMID- 7633253
TI  - Open access echocardiography. Service is valuable for evaluating murmurs too.

PMID- 7633254
TI  - Open access echocardiography. Open access to specialist opinion is preferable.

PMID- 7633255
TI  - Open access echocardiography. Service should be reserved for equivocal cases.

PMID- 7633256
TI  - Open access echocardiography. Single assessment may be dangerous.

PMID- 7633257
TI  - Open access echocardiography. Study's design leaves cost effectiveness and
      "therapeutic impact" in doubt.

PMID- 7633258
TI  - Generalists neglect psychiatry.

PMID- 7633259
TI  - Unsuspected HIV infection in first year of life. Obstetric and perinatal staff
      should provide sound, unbiased information on HIV tests.

PMID- 7633260
TI  - Patients with a self diagnosis of myalgic encephalomyelitis.

PMID- 7633261
TI  - Guidelines to reduce x ray examinations in accident departments. Radiology
      guidelines could be improved.

PMID- 7633262
TI  - Genetic testing in the classroom.

PMID- 7633264
TI  - Anaesthetists in training do not want new deal.

PMID- 7633263
TI  - Haemophilus influenzae vaccines for infants in Spain.

PMID- 7633265
TI  - Orthopaedic and trauma surgery. Best method of anterior cruciate ligament
      reconstruction is debated.

PMID- 7633266
TI  - Orthopaedic and trauma surgery. Review by Thromboembolic Risk Factors Consensus
      Group was misquoted.

PMID- 7633267
TI  - Anaesthetics training in the United States.

PMID- 7633268
TI  - Doctors are promoting expansion in non-consultant career grades.

PMID- 7633270
TI  - Hospitals pay value added tax on drugs.

PMID- 7633269
TI  - The changing role of hospital consultants.

PMID- 7633271
TI  - Postgraduate training in Italy.

PMID- 7633272
TI  - Feeding anxieties.

PMID- 7633273
TI  - Transesophageal echocardiographic study of decompression-induced venous gas
      emboli.
AB  - Transesophageal echocardiography was used to evaluate venous bubbles produced in
      nine anesthetized dogs following decompression from 2.84 bar after 120 min at
      pressure. In five dogs a pulsed Doppler cuff probe was placed around the inferior
      vena cava for bubble grade determination. The transesophageal echo images
      demonstrated several novel or less defined events. In each case where the
      pulmonary artery was clearly visualized, the venous bubbles were seen to
      oscillate back and forth several times, bringing into question the effect of
      coincidental counting in routine bubble grade analysis using precordial Doppler.
      A second finding was that in all cases, extensive bubbling occurred in the portal
      veins with complete extraction by the liver sinusoids, with one exception where a
      portal-to-hepatic venous anastomosis was observed. Compression of the bowel
      released copious numbers of bubbles into the portal veins, sometimes more than
      were released into the inferior vena cava. Finally, large masses of foam were
      routinely observed in the non-dependent regions of the inferior vena cava that
      not only delayed the appearance of bubbles in the pulmonary artery but also
      allowed additional opportunity for further reaction with blood products and for
      coalescence to occur before reaching the pulmonary microcirculation. These novel
      observations are discussed in relation to the decompression process.

PMID- 7633274
TI  - Transcranial Doppler ultrasound in commercial air divers: a field study including
      cases with right-to-left shunting.
AB  - Many cases of decompression illness occur in divers using recommended
      decompression tables. Doppler ultrasound has been used for over 20 yr and has
      shown the presence of venous bubbles in asymptomatic divers working well within
      decompression limits. Previous studies have demonstrated an increased prevalence
      of patent foramen ovale in divers who have suffered neurologic decompression
      illness. It has been postulated that right-to-left shunting through a patent
      foramen ovale could allow arterialization of these bubbles, causing symptoms and
      signs of acute decompression illness and possibly chronic subclinical neurologic
      impairment. We set out to determine the incidence of bubbles in the cerebral
      circulation of commercial divers decompressing from air dives. Using transcranial
      Doppler ultrasound (TCD), the middle cerebral arteries of 17 divers were
      monitored after surfacing from depths ranging between 3 and 50 m. Peripheral
      contrast injection with simultaneous transthoracic echocardiography and TCD was
      used to screen for right-to-left shunting. Right-to-left shunting was detected in
      four divers by TCD (one at rest, two after a Valsalva maneuver, and one only
      after coughing); however, echocardiography was positive in only one of these
      subjects after a Valsalva maneuver (TCD was positive at rest in this subject).
      Seventy-three TCD recordings were performed in four settings: 41 after underwater
      decompression, 18 after surface decompression, 10 in the interval between
      surfacing and entering the decompression chamber, and 4 after a chamber dive.
      Twenty-three of these recordings were in four subjects with right-to-left
      shunting; no bubbles were detected in any of these recordings.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7633275
TI  - Diving patterns of ama divers of Hegura Island, Japan.
AB  - Daily diving patterns, especially depth-time profiles, were continuously recorded
      during the entire work shift in four cachido and four funado divers of Hegura
      Island, Japan. All Hegura divers (cachido and funado alike) were female and
      habitually wore wet suits. Cachidos dive free and unassisted from a boat or
      float, whereas funado divers are assisted by weighted descent and during the
      ascent by being pulled by a partner into a boat on the water surface. Both funado
      and cachido divers spent 250-280 min/day on the sea at their diving locations;
      the actual diving time was 100-120 min. The divers made 90-120 dives/day to a
      depth of 13-22 m, each dive lasting approximately 60 s, considerably longer and
      deeper than those observed and recorded previously in ama divers in the Chiba and
      Miura regions. These dive profiles are similar to those reported by Paulev in
      which he observed apparent signs of decompression sickness when the subject dived
      to a depth of 15-20 m 100 times in 5 h. The average bottom time for each dive of
      Hegura funados was 23.6 s which is approximately 10 s longer than that of Korean
      female ama. The rate of ascent in the funado divers was 1.5 m/s, which is nearly
      twice that of the cachido divers (0.8 m/s). The dive frequency of Hegura funados
      (109 dives/day) was greater than the Chiba male funados (23 dives/day).
      Accordingly, cumulative bottom time of Hegura funado was 48 min/day, whereas that
      of Chiba funado was 17 min/day.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7633276
TI  - Effects of the submarine environment on renal-stone risk factors and vitamin D
      metabolism.
AB  - The effects of total sunlight deprivation on urinary risk factors for
      nephrolithiasis and vitamin D metabolism were studied in 20 healthy male
      subjects. Blood and 24-h urine samples were collected before submarine deployment
      and 68 days later while still at sea. No subject received sunlight exposure
      during the test interval. Significant decreases in daily urinary excretion of
      calcium, uric acid, sodium, sulfate, and phosphorus were found. The relative
      supersaturation ratio of monosodium urate also fell. There was no change in
      urinary citrate or urine volume. Mean serum levels of 25-hydroxyvitamin D
      [25(OH)D] declined from 31 to 19 pg/ml (P < 0.0001), parathyroid hormone
      increased from 22 to 30 pg/ml (P < 0.0001), and osteocalcin (GLA) increased from
      2.7 to 3.3 ng/ml (P = 0.005). Mean serum levels of 1,25 dihydroxy-vitamin D were
      unchanged. Four subjects had 25(OH)D levels below 10 ng/ml by the end of the
      submarine patrol. These findings suggest that exposure to the submarine
      environment produces physiologic changes that decrease the risk for renal stone
      formation. The data are consistent with the role of vitamin D metabolism in
      sunlight deprivation and demonstrate that compensatory mechanisms are well
      established within 68 days.

PMID- 7633277
TI  - Effects of hyperbaric oxygen on S-180 sarcoma in mice.
AB  - The contents of oxygen free radicals (OFRs) and malondialdehyde (MDA) in S-180
      sarcoma tissues were measured in four groups of mice: an untreated normoxic
      group, a normoxic hyperbaric group, a hyperbaric oxygen group, and an HBO group
      treated with superoxide dismutase (SOD). Measurements were done by electron
      resonance and spectrophotometry, and observations were made on the volume,
      weight, necrosis incidence rate of sarcoma tissues, and mortality in all groups.
      The OFR and MDA content in sarcoma tissues in the HBO group was significantly
      higher than those of the control groups (P < 0.001); necrosis incidence of
      sarcoma tissues and the survival rate of mice were higher; the time required for
      necrosis was shorter, and the volume and weight of sarcoma tissues were smaller
      and lighter than those of the control groups (P < 0.01). The results suggest that
      SOD cannot completely eliminate OFRs produced by hyperbaric exposure, although
      the role of HBO in producing more OFRs can be counterbalanced by SOD to a certain
      degree. Apparently HBO can check the growth rate of sarcoma and accelerate the
      necrosis of S-180 sarcoma cells.

PMID- 7633278
TI  - A modified protocol to treat early osteoradionecrosis of the mandible.
AB  - Hyperbaric oxygen (HBO) increases oxygen availability to hypoxic tissues thereby
      inducing fibroblastic proliferation and capillary formation in bone and soft
      tissue. From 1981 to 1991 we used a monoplace hyperbaric chamber, and since 1992
      a multiplace chamber, for HBO treatments. HBO was given at 2.5-2.8 atm abs for 90
      120 min, once per day. We used five to seven preoperative and five to seven
      postoperative sessions. Altogether, 17 patients with osteoradionecrosis (ORN) of
      the mandible or maxilla were treated with surgery and HBO. Surgical therapy
      consisted of decortication of the affected bone that was subsequently covered
      with a free periosteal transplant from the tibia. The shortest follow-up time is
      18 mo. Sixteen patients have remained symptom free after the first treatment
      period. One case was a failure in the early protocol but was successfully treated
      using a free microvascular flap. It is concluded that HBO is a promising adjunct
      to surgery in treating mandibular or maxillary ORN.

PMID- 7633279
TI  - An optical pressure chamber designed for high numerical aperture studies on
      adherent living cells.
AB  - We have developed an optical pressure chamber designed for use with high
      numerical aperture oil immersion microscope objectives at working pressures up to
      1,000 psi (67 atm abs). The chamber is optimized for studies of living, adherent,
      cultured mammalian cells using high resolution epifluorescence and phase contrast
      microscopy, and biophysical techniques such as fluorescence redistribution after
      photobleaching and optical trapping. The primary optical window assembly of the
      chamber can be removed and placed into a standard 35-mm tissue culture dish,
      allowing for culture, microinjection, and micromanipulation of adherent cells
      before they are loaded into the chamber. The chamber is designed to fit into a
      commercially available stage heater for temperature control, and we used a
      computer-controlled high pressure liquid chromatography pump for pressure
      control. A graphic software interface allows the user to program "dive" profiles
      and to link temperature and pressure data with digital image files of specimens
      under study. A minor modification of the present design will allow perfusion at
      high pressure.

PMID- 7633280
TI  - An alternative oxygen supply technique for the difficult patient.
AB  - A modified oxygen delivery system was developed for a patient too claustrophobic
      for the monoplace chamber or the hood in the multiplace chamber. The adaptation
      delivered O2 through the patient's tracheostomy by means of a soft cervical
      collar, a pediatric tracheostomy cuff, and a T-tube.

PMID- 7633281
TI  - A clinicopathological and immunohistochemical analysis of primary oral mucosal
      melanoma.
AB  - Nine cases of primary oral mucosal melanoma in Caucasian patients were reviewed
      and the tumours analysed for expression of S100, HMB45, NKI/C3, HLA-DR, PCNA,
      cytokeratin and von Willebrand factor. The clinical, histopathological and
      immunohistochemical features were quite distinctive and our findings support
      previous suggestions that oral melanoma should be classified as a separate entity
      rather than as a sub-type of cutaneous melanoma.

PMID- 7633282
TI  - Malignant oral tumours in Sweden 1960-1989--an epidemiological study.
AB  - Epidemiological data from the Swedish Cancer Registry of new cases of malignant
      oral tumours in Sweden 1960-1989 are presented, including the total number and
      the age-standardised incidence rate per 1 million population, by site and sex,
      (I(s)). An analysis of the various histopathological types of malignant oral
      tumours in the different sublocations is also given. A comparison is made between
      the three 10-year periods 1960-1969, 1970-1979 and 1980-1989 regarding total
      number and I(s). The total number of cases, 17,158, represented 1.8% of all newly
      diagnosed cancers in Sweden. The following relative frequencies were noted for
      the respective sites: intra-oral region 0.7%, lip 0.6% and pharynx 0.5%. The
      results indicated an increase in total number and a statistically significant
      increase of I(s) for malignant lip tumours in females over the whole period. A
      corresponding increase in total number during the periods 1960-1969 and 1980-1989
      and a decrease in I(s) during the periods 1970-1979 and 1980-1989 in lip tumours
      for males was observed. For males there was an increase in total number and a
      statistically significant increase in I(s) for malignant tongue tumours, while
      the corresponding figures for females remained constant. For malignant floor of
      the mouth tumours there was an increase in total number and a statistically
      significant increase in I(s) for both men and women. In the intra-oral region,
      including the sublocations oral cavity-other sites, tongue and floor of the
      mouth, the male:female ratio was 1.8:1 and I(s) changed from 22.8 (1960-1969) to
      29.6 (1980-1989).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7633283
TI  - Trends in oral cancer by subsite in New Zealand.
AB  - A significant increase in incidence rates for all subsites of oral cancer in men
      and all but cancer of the salivary glands in women has occurred in New Zealand
      over the past 35 years. However, only male mortality rates of cancers of the
      nasopharynx and pharynx (excluding the nasopharynx) have significantly increased
      during this time period. Significant birth-cohort effects existed in the trends
      in incidence and mortality for cancers of the tongue, mouth, pharynx (excluding
      the nasopharynx), and nasopharynx among men. For cancers of the mouth and pharynx
      (excluding the nasopharynx) an increased risk for men born 1912-1932 existed,
      while an increased risk of cancer of the tongue occurred for men born 1922
      onwards. For nasopharyngeal cancer, men born around 1912 and those born from
      about 1932 onwards were found to have an increased risk. For women, no consistent
      trends by birth-cohort were found for any oral subsite of cancer.

PMID- 7633284
TI  - Histological differentiation of oral squamous cell cancer in relation to tobacco
      smoking.
AB  - The aim of this study was to assess the potential effect of tobacco and alcohol
      consumption on the histological differentiation of oral squamous cell carcinomas
      in 161 consecutive patients. The patients were included in a prospective study to
      secure valid data on tobacco and alcohol consumption. The histopathological
      grading system included eight morphological qualities describing both the tumour
      cell population and the interaction between tumour and host. A mean histological
      score was calculated as the arithmetic mean of the scored individual
      morphological parameters. Tobacco consumption, as opposed to alcohol consumption,
      was shown to be significantly correlated with the mean histological score (P =
      0.0009), and with the four morphological qualities describing the tumour cell
      population: pattern (P = 0.0044), cytoplasmic differentiation (P = 0.0008),
      nuclear differentiation (P = 0.0054) and mitosis (P = 0.0001). Thus, tobacco
      consumption seems to cause the tumour cells of oral squamous cell carcinomas to
      undergo a more pronounced dedifferentiation which makes them more aggressive.
      This effect is enhanced with increasing exposure to tobacco smoke.

PMID- 7633285
TI  - Roles of p53 mutation in cell line establishment and identification of the
      minimum transactivation and transform suppression domains.
AB  - The mutation of the p53 tumour suppressor gene is the most frequently recognised
      genetic alteration in human cancer. We recently showed that the frequency of p53
      gene mutations in oral squamous cell carcinomas (SCCs) from which cell lines were
      established (group A) did not significantly differ from that in SCCs from which
      cell lines could not be established (group B), suggesting that the presence of a
      p53 mutation by itself is not sufficient. To assess the relevance of p53
      mutations to cell line establishment, we determined sequences of the mutated
      genes, constructed the expression plasmids, and compared biological and
      biochemical activities. Both groups contained typical mutant type mutations at a
      similar frequency. However, two mutations in group A had strong transforming
      activity. One of the mutants, codon 306 Stop mutant with C-terminal truncation,
      was found to have the transactivation and transform suppression activities
      similar to wild type. The minimum transactivation and transform suppression
      domains of p53 were thus determined based on analysis of various C-terminal
      deletions. Activity disappeared between codons 300 and 282, an interval which
      contains the C-terminal end of the sequence-specific DNA binding domain, which
      suggests that the DNA binding domain is essential for the above activities.

PMID- 7633286
TI  - Presence of human papillomavirus sequences in tumour-derived human oral
      keratinocytes expressing mutant p53.
AB  - A series of eight oral epithelial cell lines derived from untreated human oral
      squamous cell carcinomas, which had arisen in patients with different tobacco
      histories, were examined for the presence of human papillomavirus (HPV) DNA,
      expression of stable p53 protein and p53 point mutation. Polymerase chain
      reaction (PCR)-based screening, but not Southern blot analysis, showed HPV-16
      early region sequences to be present at low copy number (< 1 copy per cell) in
      two cell lines at early passage (3-5) in vitro (H400, T45), implying that only
      subpopulations of cells harboured viral DNA. HPV sequences were undetectable in
      cells at later passage (12-15), suggesting that viral sequences had been lost
      during growth in vitro, or that negative selection of HPV-containing cells had
      occurred. High levels of p53 were detected in the two HPV-positive cell lines and
      in three others (H103, H314, H357) by Western blotting, suggesting expression of
      mutant (stable) p53 molecules. A sixth cell line (H157) expressed a truncated
      p53. Sequence analysis of exons 2-11 of the p53 gene revealed missense mutations
      in six cell lines, one of which (H413) did not result in high levels of protein,
      and nonsense mutations in the remaining two cell lines (H157, H376). The results
      suggest that p53 mutation is a frequent genetic event in oral cancer. In
      addition, the expression of mutant p53 in oral cancer cells does not preclude a
      papillomaviral aetiology for these tumours. Analysis of p53 expression alone may
      result in underestimation of the frequency of p53 mutations in human
      cancers.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7633287
TI  - Influence of aging and chemoradiotherapy on leucocyte function in oral cancer
      patients.
AB  - Leucocyte functions and the influence of chemoradiotherapy were examined in three
      age groups of patients with oral cancer. The groups consisted of 66 patients
      below 65 years old (group A): 40 patients between 65 and 80 years old (group B);
      20 patients over 80 years old (group C). 20 healthy individuals (45.8 +/- 9.6
      years old) were chosen as controls. Originally, no significant differences in
      leucocyte count, CD3 population, CD4/CD8 ratio, natural killer activity or
      phagocytosis of polymorphonuclear leucocytes (PMNL) were found in the patients.
      However, T cell blastogenesis, lymphokine-activated killer cell activity and
      superoxide production of PMNL were all suppressed. These functions were further
      suppressed by cancer therapy, the greatest suppression being seen in group C.
      Compared to controls and group A, the generation of interleukin-1, interleukin-6,
      tumour necrosis factor-alpha and granulocyte-macrophage colony-stimulating factor
      were markedly suppressed in group C. These results show that very old cancer
      patients are already in an immunologically suppressed condition and that the
      leucocyte functions of these patients are further impaired by cancer therapy.

PMID- 7633288
TI  - Phase II study of cystemustine in advanced head and neck cancer. A trial of the
      EORTC Clinical Screening Group.

PMID- 7633289
TI  - Oral cancer prevention and dentists' attitude towards smoking.

PMID- 7633290
TI  - European School of Oncology Advisory report to the European Commission for the
      Europe Against Cancer Programme: oral carcinogenesis in Europe.
AB  - A European School of Oncology Advisory Group has reviewed current knowledge on
      the epidemiology, treatment and prevention of cancer of the oral cavity. While
      the major factors in the aetiology of such cancers are thought to be well
      understood, i.e. tobacco and alcohol consumption, current increases in the
      occurrence of the disease, especially in young adults throughout Europe, are
      cause for concern. The reasons for such increases are not clearly evident and the
      Advisory Group has suggested further work which is required to be carried out to
      understand the aetiology. In treatment of the disease there have been no major
      improvements in survival for patients in recent decades and the importance of
      examining new radiotherapy modalities and defining the role of chemotherapy is
      emphasized. Primary prevention of oral cancer could be achieved by stopping
      smoking tobacco, limiting alcohol consumption to a minimum (2-3 drinks per day)
      and increasing intake of fruits and vegetables. To supplement these actions,
      while neither population screening programmes nor screening trials could be
      recommended by the Advisory Group, initial chemoprevention trials have produced
      some promising results and this represents an interesting area which is the focus
      of much current research.

PMID- 7633291
TI  - Ameloblastoma: biological profile of 3677 cases.
AB  - Available literature on ameloblastoma of the jaw was reviewed, including
      publications from 1960 to 1993, and compared to the latest larger review,
      published by Small and Waldron in 1955. The average age of patients with
      ameloblastoma is 36 years. In developing countries ameloblastomas occur in
      younger patients. Men and women are equally affected. Women are 4 years younger
      than men when ameloblastomas first occur, and the tumours appear to be larger in
      females. Dominant clinical symptoms such as painless swelling and slow growth are
      non-characteristic. The ratio of ameloblastoma of the mandible to maxilla is 5 to
      1. Ameloblastomas of the mandible occur 12 years earlier than those of the
      maxilla. Ameloblastomas occur most frequently in the molar region of the
      mandible. In Blacks, ameloblastomas occur more frequently in the anterior region
      of the jaws. Radiologically, 50% of ameloblastomas appear as multilocular
      radiolucent lesions with sharp delineation. Histologically, one-third are
      plexiform, one-third follicular; other variants such as acanthomatous
      ameloblastoma occur in older patients. Two percent of ameloblastomas are
      peripheral tumours. Unicystic ameloblastomas occurring in younger patients have
      been found in 6%. Detailed data on 345 patients with ameloblastoma were evaluated
      for clarification of therapeutic approaches. Chemotherapy and radiation seem to
      be contraindicated. Ameloblastomas of the maxilla should be treated as radically
      as possible, ameloblastomas of the mandible should also be treated radically.
      However, ameloblastomas which radiologically appear as unilocular lesions may be
      treated conservatively (enucleation, curettage), whenever all areas of the cystic
      lumen are controllable intraoperatively. Unicystic ameloblastomas occurring in
      patients 15 years younger than those with multisystic ameloblastoma may be
      treated conservatively except in cases with invasion of epithelium into the cyst
      wall. Different recurrence rates have been found for histological variants of the
      ameloblastoma. Follicular ameloblastomas appear to recur more often than the
      plexiform type. Unicystic ameloblastomas reveal lower recurrence rates than "non
      unicystic" ameloblastomas. The peripheral type of ameloblastoma may be excised,
      since conservative therapy results in low recurrence rates. Postoperative follow
      up is most important in the therapy of ameloblastoma, because more than 50% of
      all recurrences occur within 5 years postoperatively.

PMID- 7633292
TI  - Quantitative and qualitative research in the addictions: an unhelpful divide.

PMID- 7633293
TI  - An investigation of self-efficacy, partner support and daily stresses as
      predictors of relapse to smoking in self-quitters.
AB  - Six hundred and thirty smokers who intended to quit smoking themselves completed
      pre-cessation measures of self-efficacy, partner support, daily stresses and
      demographics. Subjects were contacted at 2, 7, 14, 30, 90 and 180 days post
      cessation to determine smoking status and to re-administer the measures at 7, 14
      and 30 days post-cessation. A series of logistic regression examined which
      prospective factors best predicted relapse between 0-2 days, 3-7 days, 8-14 days,
      15-30 days, 31-90 days and 91-180 days. Relapse was predicted by different
      variables at different times; however, self-efficacy was a consistent predictor
      of relapse over time.

PMID- 7633294
TI  - Alcohol licensing system changes and alcohol consumption: introduction of wine
      into New Zealand grocery stores.
AB  - New Zealand permitted grocery stores to sell table wine products beginning April
      1990 with the implementation of a new Sale of Liquor Act. The number of licensed
      outlets for retail sales of wine for consumption off-premises increased
      substantially. Using an interrupted multiple time-series design with nation-wide
      quarterly alcohol sales data from 1983 to 1993, we assessed the effects of the
      policy change on sales of wine. Results from Box-Jenkins time-series models
      revealed a 17% increase in wine sales associated with the introduction of wine
      grocery stores. Increased sales were limited to the specific category of
      alcoholic beverages permitted in grocery stores--table wine. Sales of fortified
      wine, distilled spirits and beer did not increase. We conclude that expansion in
      retail availability of wine is associated with increased sales and consumption.

PMID- 7633295
TI  - Intoxication and hazardous use of alcohol: results from the 1992 Finnish Drinking
      Habits Study.
AB  - The harmful or risky use of alcohol among the Finnish population is studied on
      the basis of data gathered in a national survey. Harms are examined in relation
      to different styles of drinking, and they are measured using both the Alcohol Use
      Disorders Identification Test (AUDIT) and the 1992 Drinking Habits Study of the
      Finnish Foundation for Alcohol Studies. Using an alcohol score of 11 as the cut
      off point, 22% of men and 5% of women can be classified as risky drinkers. Young
      age and family relations are related positively to the prevalence of risky
      drinking. High scores in the youngest age group (15-19 years) are related to the
      intoxication-seeking drinking style. Those who drink often and large amounts on
      individual occasions experience the most harm related to drinking. However, those
      who drink seldom but more than seven units on a single occasion also experience
      harmful consequences fairly often and, thus can have high AUDIT scores.
      Significant others commonly criticize or give advice to the hazardous drinkers.
      Doctors or employers had paid less attention to the intoxication seeking or heavy
      drinking than the police or the significant others.

PMID- 7633296
TI  - Drunkenness among police detainees.
AB  - All detainees at seven police stations within the Metropolitan Police Area were
      observed by the authors. Continuous 24-hour cover was provided at each station
      for periods of 3 weeks. The number of people arrested for offences of drunkenness
      was noted, as was the apparent degree of drunkenness of all detainees,
      irrespective of arrest offence. Arrest for drunkenness in London was strongly
      associated with being white and with having been born in Scotland or Ireland.
      Within the confines of the station, being drunk was associated with
      aggressiveness, with the need for medical examination and with delays in
      implementing interview procedures. The physical condition of many chronically
      drunk people was very poor and evidence of long-term self neglect was common.
      Formal cautioning of drunkenness offenders has effectively removed such people
      from the courts; in the present study only 5% of those arrested for drunkenness
      alone were subsequently charged. Despite this the police in London must continue
      to arrest and detain the drunk and incapable for want of suitable alternatives.

PMID- 7633297
TI  - Predictors of help-seeking and the temporal relationship of help to recovery
      among treated and untreated recovered problem drinkers.
AB  - This study investigated variables predicting different help-seeking patterns (no
      treatment, AA participation only, or treatment plus AA participation) by problem
      drinkers who had maintained stable abstinence (n = 57). Collaterals verified
      subjects' help-seeking and drinking status. Help-seeking was predicted by greater
      alcohol-related psycho-social problems, especially in interpersonal
      relationships, but was not associated with heavier drinking practices or
      demographic characteristics. Subjects' belief that they could solve their own
      problem deterred help-seeking, whereas relationship problems and being unable to
      quit on one's own facilitated help-seeking. Additional incentives specific to AA
      were its privacy, anonymity, spiritual aspects, opportunities to help other
      problem drinkers, and the convenient meetings held at times typically spent
      drinking. Many subjects became abstinent before they sought help, especially from
      treatment programs. These findings implicate interpersonal factors as primary
      incentives for help-seeking and suggest that interventions often consolidate,
      rather than initiate, positive changes in drinking practices.

PMID- 7633298
TI  - Prompting alcoholics to be referred to an alcohol clinic: the effectiveness of a
      simple letter.
AB  - Many patients received in emergency units (EU) of hospitals present alcohol
      related problems. Most are alcohol dependent or abusers and enter for
      drunkenness, stay a few hours and return home. To assess the effectiveness of a
      letter referring these patients to an outpatient alcoholism treatment clinic, we
      performed a randomized study. For 6 months, all the patients who had been
      diagnosed as alcoholic, who had an address and who had not consulted a physician
      for alcoholism in the 6 previous months were selected from the records of the EU
      of a French university hospital. At least 2 days after their stay in the EU, we
      sent a letter to 181 patients of an experimental group (group E) suggesting they
      make an appointment with a physician specializing in alcoholism. No letter was
      sent to 181 patients in a control group (group C). Six months later, 21 patients
      (11.2%) of group E had called the outpatient alcoholism treatment clinic to make
      an appointment and came to a consultation. Two of the 181 patients of group C
      came to the consultation. The effectiveness of this method for referring
      alcoholics to a clinic had been controlled by another prospective study. We
      concluded that sending a letter 2 days after the passage of an alcoholic to an EU
      for drunkenness is a useful method of referral to an outpatient alcoholism
      treatment clinic.

PMID- 7633299
TI  - The introduction of a methadone prescribing programme to a drug-free treatment
      service: implications for harm reduction.
AB  - In 1990, a National Health drug treatment service with a non-opiate prescribing
      policy introduced an oral methadone treatment programme for problem opiate users,
      in addition to existing counselling services. The present study aimed to evaluate
      the implications of this policy change by comparing two client groups in terms of
      defined harm reduction variables. The groups consisted of 39 clients presenting
      to the service prior to methadone prescribing (pre-methadone group), and 41
      clients who attended for treatment after methadone prescribing had commenced
      (post-methadone group). Data analysis revealed that 83% of the post-methadone
      group remained in treatment for longer than 6 months, in comparison with 13% of
      clients in the pre-methadone group (p < 0.00001). Other significant differences
      were noted in treatment outcome, where findings indicated that clients in the
      post-methadone group were more likely to report cessation of injecting behaviour
      and continued illicit drug use. Detected crime in the post-methadone group was
      reduced, and greater positive change in terms of personal relationships was
      reported. The study concludes that the introduction of a methadone treatment
      programme appears to have improved treatment outcome significantly for problem
      opiate users presenting in the service.

PMID- 7633300
TI  - Investigating the influence of treatment philosophy on outcome of methadone
      maintenance.
AB  - This study is based on a 'natural experiment' in which a cohort of heroin users
      was assessed at one unit, then referred on geographic grounds for treatment to
      one of two clinics--one orientated to long-term maintenance (Clinic 2, with 61
      subjects), the other to time-limited treatment aimed at achieving abstinence from
      all drugs including methadone (Clinic 1, 141 subjects). The outcome measure was
      heroin use as measured by urine testing performed regularly at both clinics.
      Overall, 25% of urine tests from Clinic 1 were positive for heroin compared to
      18% in Clinic 2. This difference reflected in part a high rate of heroin use
      during the period of mandatory withdrawal from treatment in clinic 1. Statistical
      models were developed to identify factors associated with heroin use. There was a
      strong association between methadone dose and heroin use; relative to a daily
      dose of 40 mg, a dose of 80 mg/day of methadone was less likely to be associated
      with a heroin-positive urine (OR 0.55, 95% CI [0.45, 0.68]). Average doses
      prescribed in Clinic 1 were lower, reflecting the clinic's orientation to
      abstinence. Adjusting for dose, and for the fact that certain individuals tend to
      use heroin heavily while others do not, there was no difference between the
      clinics in risk of heroin use during maintenance treatment. The higher rates of
      heroin use in the abstinence-orientated clinic were attributable to time-limited
      treatment and the use of lower doses of methadone. This finding confirms that in
      investigating the effects of treatment factors, the powerful influence of
      methadone dose needs to be taken into account.

PMID- 7633301
TI  - The apomorphine test in heroin addicts.
AB  - Chronic administration of opiates to laboratory animals induces supersensitivity
      of the dopamine receptors in the cerebral areas innervated by the
      mesotelencephalic dopamine pathways. In humans, the in vivo study of the
      sensitivity of the dopamine neurotransmitter system in Parkinson's patients can
      be done by means of the apomorphine test, which consists of measuring the number
      of yawns induced by the subcutaneous administration of low doses of apomorphine
      (0.005 mg/kg). If chronic opiate use in humans, as in experimental animals,
      results in supersensitivity of the dopamine systems, the apomorphine test could
      differentiate between heroin addicts and healthy volunteers, with the former
      showing greater number of yawns. In order to test this hypothesis we carried out
      the apomorphine test in two groups of subjects: a group of male heroin addicts
      attending our Addiction Treatment Centre for detoxification and the other group
      consisting of healthy volunteer male university students. Results showed that
      subcutaneous apomorphine administration induced a greater number of yawns (p <
      0.05) in the group of heroin addicts as compared with the group of healthy
      volunteers, suggesting that heroin addicts present an enhanced sensitivity of the
      dopamine nuerotransmitter system.

PMID- 7633302
TI  - Factors that characterize street injectors.
AB  - Injecting drugs in the streets and other public places is increasingly common in
      many cities and large towns in the United Kingdom. It is a practice rarely open
      to view, but the evidence is there in the used needles and syringes left in
      stairwells of flats, shop doorways, public toilets and other areas where exposure
      can be avoided. Although it is a development with serious implications for public
      health, it has received little research attention. This paper reports the factors
      associated with street injecting from 56 polydrug users who regularly injected in
      public places. It reveals that they were more likely to be severely drug
      dependent with associated health problems. A high proportion were homeless. Their
      drug-related and sexual risk behaviour have implications for the acquisition and
      transmission of disease.

PMID- 7633303
TI  - Organization of the treatment and supervision of heroin addiction.

PMID- 7633304
TI  - Alternative religion and outcome of alcohol dependence in Brazil.

PMID- 7633305
TI  - Comment on 'US alcohol consumption, abuse and dependence'.

PMID- 7633307
TI  - Minimal residual disease in leukaemia.

PMID- 7633306
TI  - Expenditure analysis for planning health services in developing countries.

PMID- 7633308
TI  - The familial breast cancer genes--the end or the beginning?

PMID- 7633309
TI  - Cost of health services provided at a primary health centre.
AB  - BACKGROUND: Information on the cost of health services is essential for good
      planning and management and leads to an efficient use of resources. Very little
      information on this is available in India. We estimated the distribution of costs
      incurred on the Primary Health Centre, Chhainsa, Haryana by the type of service
      provided and their average unit costs. METHODS: We calculated the total costs
      incurred in running the primary health centre for one year using standard costing
      methods. This cost was apportioned under different heads on the basis of time and
      space utilization. The number of activities carried out, between April 1991 and
      March 1992, was obtained from the monthly reports of the centre maintained by the
      health assistant and supervised by the medical officer. RESULTS: The total cost
      incurred for one year was Rs 777,020 (US$ 24,250). Curative care accounted for
      32% of the total costs followed by communicable disease control (17%), child care
      (17%), maternal care (11%) and family welfare (10%). An expenditure of Rs 24 was
      incurred on each outpatient. The cost of giving full primary immunization to a
      child was estimated at Rs 131, while Rs 127 was incurred on providing antenatal,
      natal and postnatal care to each pregnant woman. Tuberculosis-related activities
      in the community cost Rs 3 per head per year and malaria-related activities Rs 2
      per head per year. The cost incurred annually on family welfare services to an
      eligible couple was Rs 19. CONCLUSIONS: Our findings suggest that the cost
      estimates from this primary health centre are comparable with the estimates from
      other developing countries. These cost estimates may be used to determine user
      fees by health agencies or for premiums for community health insurance schemes.

PMID- 7633310
TI  - Potential years of life lost by major childhood cancer deaths in Bombay.
AB  - BACKGROUND: Over the last two decades mortality from childhood cancers has
      declined in the West, possibly due to advances in chemotherapy. Unfortunately,
      poor countries cannot afford these drugs as they are costly and scarce. We
      undertook this study in Bombay to help us make rational choices in this area.
      METHODS: We studied the mortality, incidence and years of potential life lost by
      premature death from specific cancers in children under 15 years of age. RESULTS:
      Leukaemia accounted for 30% to 50% of premature life lost by death from cancers
      regardless of gender or age, i.e. if such loss was avoided by timely diagnosis
      and therapy, up to 50% gain of person-life would occur. It constituted nearly one
      third of the childhood cancers, with age-adjusted rates comparable with American
      blacks and whites in boys, but less in girls. Incidence and decline of mortality
      due to leukaemia from 1964 was lower in girls than in boys. CONCLUSIONS: A focus
      on leukaemia treatment would increase productive person-life by nearly 50%. A
      triaging system might be the best method for allocating treatment till data on
      cost of such therapy are available. There is a need to increase morphological
      diagnoses in girls. Concentrating on treating girls with leukaemia older than 5
      might contribute most in terms of gain in human potential and would be a cost
      effective use of scarce resources.

PMID- 7633311
TI  - Postal follow up of patients with epilepsy.
AB  - BACKGROUND: Epilepsy services in India are mostly located in urban areas and are
      often overcrowded. It is difficult, therefore, to organize long term management
      programmes. We report our experience at a tertiary referral centre on follow up
      of patients with epilepsy through regular postal review. METHODS: One hundred
      consecutive patients with epilepsy (63 men, 37 women, mean age 17 years) who had
      only seizures were followed up by post using a questionnaire, instead of
      reviewing them in a clinic. The safety, utility and efficiency of this system
      were evaluated. RESULTS: Sixty patients had generalized seizures, 30 had complex
      partial seizures and 10 had other types of seizures. The indication for shifting
      to postal review was good control of seizures in 87 cases and economic reasons in
      the remaining. Postal review constituted 60% of the total follow up period in 55
      cases. Sixty-six patients could be maintained on postal review which was
      suspended or discontinued in 34 patients. Of these 34, 16 were returned to it
      after being seen in the clinic on a further occasion. Poor control of seizures,
      fresh medical or social problems, lack of confidence or a combination of these
      were the reasons for discontinuing the postal review. The economic benefit to a
      patient by way of savings in travel, incidental expenses and lost wages was
      estimated to be Rs 750 per annum. The work load in the epilepsy clinic was
      decreased by 40%. No serious medical problems or mortality were reported in the
      study population. CONCLUSION: Systematic postal review is a cost-effective
      alternative to clinic review in the long term follow up of a certain group of
      patients with epilepsy.

PMID- 7633312
TI  - Insulin treatment in non-insulin dependent diabetes mellitus.
AB  - Non-insulin dependent diabetes mellitus (NIDDM) is an important cause of
      morbidity and mortality, both in developed as well as in developing countries.
      The eyes, kidneys, and cardiovascular and neurological systems are predominantly
      affected by this chronic disease, leading to loss of employment and sometimes
      life. The most common setting is uncontrolled glycaemia after dietary
      restriction, exercise and oral hypoglycaemic drug therapy. Insulin may be needed
      for treating NIDDM some time during the course of the disease. Insulin therapy
      results in improved beta-cell function, a decrease in the hepatic glucose output
      and an improvement of the lipoprotein profile. Some of these beneficial effects
      are due to nullification of 'glucose toxicity'. Objective evidence of a link
      between tight metabolic control and chronic complications of NIDDM is still not
      established, despite the results of recent trials. Many insulin regimes have been
      tried. Recently, attention has been focused on combination therapy with
      sulphonylureas and insulin, using long-acting insulin at bedtime only. This
      regime improves the glycaemic profile (due to a reduction of hepatic glucose
      output), using lower doses of insulin and sulphonylureas. However, experience
      with this regime suggests that it is only suitable for a subset of NIDDM
      patients. Adverse effects of insulin therapy include weight gain and
      hypoglycaemia, which can usually be easily managed. It is hyperinsulinaemia, with
      its complex array of adverse metabolic effects, that has recently concerned
      physicians. Acceleration of atherosclerosis, hypertension and worsening of the
      lipoprotein profile have been cited as possible adverse effects. The presence of
      such dysregulation is included in the recently described syndrome X.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7633313
TI  - Keyhole surgery in India.

PMID- 7633314
TI  - PCR for the detection of Mycobacterium tuberculosis DNA.

PMID- 7633315
TI  - HIV and prisons.

PMID- 7633316
TI  - HIV-control programme in Thailand.

PMID- 7633317
TI  - Conservative management of chronic renal failure.

PMID- 7633318
TI  - Management of Rhesus isoimmunization.

PMID- 7633320
TI  - Selection and management of the brain dead donor.

PMID- 7633319
TI  - The GATT-TRIPS agreement.

PMID- 7633321
TI  - Basal cell carcinoma of the scrotum.

PMID- 7633322
TI  - Resident doctors' strike at AIIMS.

PMID- 7633323
TI  - Pitfalls in the way of today's physician.

PMID- 7633324
TI  - Was it actually plague?

PMID- 7633325
TI  - Neurotransmitter and neuromodulatory mechanisms involved in alcohol abuse and
      alcoholism.
AB  - Acute or chronic consumption of alcohol interferes differentially with
      transmission processes in the CNS, affecting many--if not all--of the known
      neurotransmitter systems. Conversely, selective pharmacological manipulations of
      some of these neurotransmitter systems have been shown to reduce ethanol intake
      and preference as well as the severity of the ethanol withdrawal syndrome in
      animal models, certain compounds having even been employed successfully in the
      clinic. This review examines the studies which have attempted to elucidate the
      roles of these neurotransmitter systems in the mechanisms involved in the various
      aspects of alcohol abuse and alcoholism, with an emphasis on recent developments.
      The brain's major amino acid transmitter systems--inhibitory gamma-aminobutyric
      acid (GABA) and excitatory glutamate--have been widely studied over the past
      decade, with the general consensus that acute ethanol facilitates GABAergic
      transmission (by enhancing chloride conductance through the GABAA receptor) and
      inhibits glutamatergic function (by decreasing cationic conductance through the
      NMDA receptor). Conversely, the development of tolerance associated with chronic
      ethanol consumption leads to a reduced GABAergic and increased glutamatergic
      function. Interactions between ethanol and the monoaminergic transmitter systems
      are complex. Dopaminergic and noradrenergic mechanisms, along with the endogenous
      opioid systems of the brain, seem to be implicated in the rewarding effects of
      ethanol via activation of positive reinforcement pathways, while the serotonergic
      system mediates negative reinforcement. A number of ligands of the dopaminergic,
      serotonergic and opioidergic receptors involved in ethanol consumption-related
      behaviors have been recognized for their effects in reducing ethanol preference
      and/or alleviating symptoms of the ethanol withdrawal syndrome in various animal
      models. Several of these substances are being used with success clinically.
      Studies of the central cholinergic system in alcoholics have provided clues to
      the mechanisms underlying the deleterious effects of ethanol on learning and
      memory, and evidence of a reduced central cholinergic activity has been reported
      in alcohol-dependent patients. Interestingly, acetylcholine-rich grafts and
      cholinomimetic drugs have been found to ameliorate ethanol-induced behavioral
      deficits in alcoholized rats. More generally, basic studies on alcohol's effects
      on central neurotransmission certainly hold the key to the development of new
      strategies for the treatment of alcoholism.

PMID- 7633326
TI  - Critique. The involvement of neuromediation in alcohol abuse and alcoholism.

PMID- 7633327
TI  - Differential reactivation by HI-6 in vivo of paraoxon-inhibited rat brain
      acetylcholinesterase molecular forms.
AB  - The effects of the cholinesterase reactivator HI-6, [1-(((4-(aminocarbonyl)
      piridinio)methoxy)methyl-2-(hydroxy- imino)methyl pyridinium dichloride], on
      paraoxon-inhibited brain acetylcholinesterase (AChE) and its molecular forms were
      studied in rats. Treatment with paraoxon (0.25 mg/kg s.c.) caused approx. 60%
      inhibition of total AChE from frontal cerebral cortex, while that including HI-6
      (140 mg/kg i.m.) and atropine (50 mg/kg i.m.) reduced such inhibition to only
      25%. Two molecular forms of the enzyme, 10S and 4S, corresponding to globular
      tetrameric (G4) and monomeric (G1), were detected by sucrose gradient
      sedimentation. In paraoxon treated rats the G4 form was inhibited by approx. 65%
      while G1 only by 35%. The G4 form was considerably and selectively reactivated by
      HI-6 while the G1 form was not reactivated at all. The data show that HI-6
      penetrates the blood-brain barrier and reactivates the molecular forms
      preferentially inhibited by paraoxon and involved in synaptic neurotransmission.

PMID- 7633328
TI  - Chronic parenteral antidepressant treatment in rats: unaltered levels and
      processing of neuropeptide Y (NPY) and corticotropin-releasing hormone (CRH).
AB  - We have previously reported elevated brain tissue contents of neuropeptide Y-like
      immunoreactivity (NPY-LI) following 3 weeks of oral treatment with the
      antidepressants zimelidine and imipramine. Other studies have not reproduced this
      finding. To eliminate the possibility that this has been due to insufficient
      treatment duration, dosage, or differences in route of administration or assay
      specificity, we have administered the selective serotonin reuptake inhibitor
      citalopram and the preferential noradrenaline reuptake inhibitor
      desmethylimipramine parenterally for 6 weeks. NPY-LI was assayed using both the
      assay employed in the original study, and an assay based on a different antiserum
      which has been extensively examined for cross-reactivity. To exclude the
      possibility that differential processing rather than altered synthesis rate is
      responsible for apparent changes in NPY-LI, HPLC analysis of immunoreactive
      fragment profiles was used. No differences in NPY-LI levels were seen in the
      brain regions examined, and no differences in HPLC profiles of NPY-LI were
      present with either drug. We conclude that chronic parenteral administration of
      antidepressant drugs in naive (non-depressed) animals does not affect the
      synthesis or processing of NPY. Another neuropeptide implicated in mechanisms of
      depression, corticotropin-releasing hormone (CRH) was also found to be unaffected
      by a similar analysis.

PMID- 7633329
TI  - In vivo modification of GABAA receptor with a high dose of pyridoxal phosphate
      induces tonic-clonic convulsion in immature mice.
AB  - The biologic cofactor, pyridoxal-5'-phosphate (PLP), is responsible for tonic
      clonic convulsion in immature mice. The mechanisms underlying such convulsive
      fits induced by administration of a single high dose of PLP were studied. The
      administration of PLP resulted in a 13% increase of PLP in the P2 fraction
      compared to control P2, and the calculated data suggested that membrane bound PLP
      increased over 31% (approximately 1 microM). The P2 fraction of administered mice
      was treated with [3H]NaBH4 and analyzed by SDS-polyacrylamide gel
      electrophoresis. The radioactivity was mainly incorporated into a 52 kDa protein
      which corresponded to a GABAA receptor subunit. The addition of PLP in vitro
      competitively inhibited [3H]GABA binding as well as [3H]flunitrazepam binding to
      synaptic membranes in a concentration-dependent manner, and 50% inhibition was
      achieved with 1 mM PLP. The results obtained in the present study demonstrate
      that PLP was rapidly permeable into the brain through the immature blood-brain
      barrier and then bound directly to GABAA receptor. It is probable that specific
      amino groups of lysine residues on the GABAA receptor react in vivo with PLP to
      form Schiff bases, and that the in vivo modification of the receptor produces a
      degeneration of GABAergic neurotransmission leading to the onset of a convulsive
      fit.

PMID- 7633330
TI  - Transient coupling of NMDA receptor with ip3 production in cultured cells of the
      avian retina.
AB  - The mobilization of inositol triphosphate ip3 by N-methyl D-aspartate (NMDA) and
      kainate, two excitatory amino acid EAA receptor agonists, was studied in cultured
      chick retina cells as a function of culture differentiation. Kainate (EC50 = 30
      microM) stimulated from 6 to 9-fold the production of [3H]ip3 between E8C3
      (embryonic day 8 plus 3 days in vitro) and E8C13. The kainate response was
      blocked by CNQX (100 microM) by more than 80% until stage E8C9. MK-801, however,
      was totally ineffective in preventing the kainate induced ip3 generation. [3H]ip3
      production evoked by NMDA was increased 4-fold above basal levels at E8C3. As
      cultures differentiated, [3H]ip3 production promoted by NMDA decreased to 2.5
      fold at E8C6 to 1.6-fold the basal levels in cultures at later stages of
      differentiation. The removal of Mg2+ from the incubating medium at E8C3 increased
      the NMDA mediated [3H]ip3 production by 80%. However, at more differentiated
      stages of the cultures, when cells were not responsive to NMDA, removal of Mg2+
      plus the addition of 1 mM glycine did not change the pattern of the response.
      Although NMDA mediated ip3 production is almost absent in more differentiated
      cultures, NMDA is able to induce [3H]GABA release in E8C3 and E8C13 cultures with
      characteristics that reflect typical NMDA receptor activation: it is highly
      potentiated by the absence of Mg2+ and by the presence of glycine. The NMDA
      induced production of [3H]ip3 at E8C3 was entirely blocked by MK-801 (100 microM)
      and APV (100 microM) but not by CNQX.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7633331
TI  - Effect of phenylalanine and alpha-methylphenylalanine on in vitro incorporation
      of 32P into cytoskeletal cerebral proteins.
AB  - We studied the effects of L-phenylalanine and alpha-methylphenylalanine on 32P in
      vitro incorporation into cytoskeletal proteins from cerebral cortex of 17-day-old
      rats. Slices of cerebral cortex were incubated in the absence or presence of
      increasing concentrations of L-phenylalanine, alpha-methylphenylalanine or L
      phenylalanine plus alpha-methylphenylalanine for 1 h. The cytoskeletal fraction
      obtained from slices was incubated in the presence of the same drugs and the 32P
      in vitro incorporation into cytoskeletal proteins was measured. Addition of alpha
      methylphenylalanine did not change 32P in vitro incorporation into the
      cytoskeletal proteins, but phenylalanine decreased the in vitro phosphorylation
      of beta tubulin. Furthermore, addition of L-phenylalanine plus alpha
      methylphenylalanine decreased the in vitro phosphorylation of both 160 kDa
      neurofilaments and alpha-tubulin.

PMID- 7633333
TI  - Regional and age-dependent differences in the affinity of dopamine D2 agonist
      binding in the rat brain.
AB  - In sagittal brain sections of newborn male rats (1-day-old) there were no
      regional differences in the IC50 values of dopamine at [125I]iodosulpride binding
      sites. In contrast, in 20- and 60-day-old rats, there was a selective increase in
      the IC50 values of dopamine in the nucleus accumbens, caudate-putamen, and
      olfactory tubercule. The IC50 values of these regions decreased in 262-day-old
      rats. Some of the other brain areas appeared to behave in a similar, but much
      less pronounced, fashion. Thus, there were significant regional differences in
      the IC50 values of young, adult, and old rats. In addition, there was a rapid
      increase in [125I]iodosulpride binding between the newborn and the 20-day-old
      rats, which leveled off thereafter, and selectively decreased in the substantia
      nigra of the 262-day-old rats. In conclusion, these results indicate that a
      biphasic decrease-increase in the affinity of D2 agonist binding sites occurs
      selectively in the basal ganglia. These findings may be of relevance for
      developmental diseases in which dopaminergic mechanisms have been implicated,
      such as schizophrenia and Parkinson's disease.

PMID- 7633332
TI  - Involvement of adenosine deaminase and adenosine kinase in regulating
      extracellular adenosine concentration in rat hippocampal slices.
AB  - In this study the relative importance of adenosine deaminase and adenosine kinase
      in regulating extracellular adenosine concentration was investigated in rat
      hippocampal slices labelled with [3H]-adenine. The release of [3H]-purines evoked
      by electrical stimulation or energy depletion (oxygen and glucose deprivation)
      was measured and, using high-performance liquid chromatography (HPLC), the
      proportion of [3H]-label in the form of [3H]-adenosine, [3H]-inosine and [3H]
      hypoxanthine was determined. In addition, endogenous purine release was measured
      by HPLC with UV detection. 10 microM 5-iodotubericidin (5-IT), an inhibitor of
      adenosine kinase, significantly increased endogenous adenosine release and
      altered the pattern of [3H]-purine release by increasing the proportion released
      as [3H]-adenosine, under basal conditions and after electrical stimulation or
      energy depletion. 5 microM erythro-9-(2-hydroxy-3-nonyl) adenosine (EHNA), an
      inhibitor of adenosine deaminase, also increased endogenous adenosine release and
      altered the pattern of [3H]-purine release evoked by energy depletion by
      decreasing the proportion of [3H]-label released as [3H]-hypoxanthine and [3H]
      inosine, whilst approximately doubling that of [3H]-adenosine. In contrast,
      adenosine release was not altered by EHNA under basal conditions or electrical
      stimulation. It is concluded that under conditions which provide adequate oxygen
      and glucose, adenosine kinase plays a much greater role than adenosine deaminase
      in regulating the extracellular concentration of adenosine. However, adenosine
      deaminase becomes important in regulating extracellular adenosine concentration
      when adenosine formation is increased by energy depletion.

PMID- 7633334
TI  - Biochemical and pharmacological evidence for the presence of A1 but not A2a
      adenosine receptors in the brain of the low vertebrate teleost Carassius auratus
      (goldfish).
AB  - In whole brain membranes of goldfish, 3H-chlorocyclopentyladenosine bound to
      adenosine A1 receptors. The A1 receptors were ubiquitously distributed in the
      brain with a maximum in the hypothalamus and a minimum in the spinal cord. In
      superfused goldfish cerebellar slices, cyclohexyladenosine inhibited the cyclic
      AMP accumulation stimulated by forskolin and the selective adenosine A1 receptor
      antagonist, 8-cyclopentyltheophylline, reversed this effect. In the same brain
      preparation, 30 mM K+ stimulated the release of glutamate, glutamine, glycine and
      GABA in a Ca(2+)-dependent manner, whereas the aspartate and taurine release was
      Ca(2+)-independent. Cyclohexyladenosine, in a dose-dependent manner, inhibited
      the 30 mM K(+)-evoked release of glutamate whereas that of aspartate was
      unaffected. The CHA inhibition of glutamate-evoked release was reversed by 8
      cyclopentyltheophylline. The adenosine A2a receptors were not detectable in whole
      brain membranes of goldfish either using the specific agonist 3H-CGS 21680 or 3H
      5'-N-ethylcarboxamidoadenosine. The presence of A2b seems to be suggested by the
      NECA stimulation of cyclic AMP accumulation, which was reversed by 8
      cyclopentyltheophylline. The results, taken together, indicate that adenosine has
      a neuromodulatory function in the nervous system of lower vertebrates which is
      comparable to that described in mammalian brain.

PMID- 7633335
TI  - The importance of research to society.

PMID- 7633336
TI  - Sleep during the week before labor: relationships to labor outcomes.
AB  - This correlational study was conducted to examine the relationship between
      maternal sleep during the nights prior to the onset of labor and labor outcomes
      of length, type of delivery, and maternal perceptions of labor. Subjects (N = 99)
      were drawn from childbirth education classes at a women's hospital in the
      southeastern United States. Subjects completed the Visual Analog Sleep Scale each
      morning, beginning two weeks prior to their due dates. Following delivery,
      subjects completed the Perception of Labor and Delivery Scale, and researchers
      gathered data about their labors. These women reported poor sleep effectiveness
      coupled with high sleep disturbance; however, there were no significant
      correlations between sleep quality and length of labor or maternal perceptions of
      labor for either the night, or the week, prior to the onset of labor. This
      finding leads us to question the view that disturbed prenatal sleep will
      interfere with the progress of labor and lead to more cesarean sections.

PMID- 7633337
TI  - The effect of pain on infant behaviors.
AB  - Facial, body, and cry behaviors, heart rate, palmar sweating, and acoustic cry
      measures were compared across differing levels of infant pain. Eighty-eight
      infants were placed in a 16-cell matrix of 4 ages (0 to 3 mo., 4 to 6 mo., 7 to 9
      mo., and 10 to 12 mo.) and levels of pain (LOP) (none, mild, moderate, severe)
      with 5 to 6 infants occupying each cell. Matrix placement was determined by
      agreement of > 75% among five pediatric clinical nurse specialists who viewed
      videotapes and read information about the infant's history, diagnosis, medical
      and/or surgical status, medications, and nutritional/fluid status. Coded infant
      behaviors and acoustic cry parameters were compared using a 2-level (LOP, age)
      MANOVA. Behaviors that differed across LOP were influenced by infant development.
      Facial expressions were clinically useful LOP indicators only for 0- to 3-month
      old infants. Facial and body behaviors and cry measures that differed across LOP
      in younger infants did not differ in older infants due to the development of
      intentionality. Cry orientation and consolability may be useful clinical
      indicators of pain with older infants.

PMID- 7633338
TI  - Chemical dependency and adolescent self-esteem.
AB  - The purpose of this descriptive study is to determine whether self-esteem differs
      between chemically dependent adolescents and adolescents from the general high
      school population. The Self-Esteem Inventory (Coopersmith, 1987) was completed by
      119 adolescents (31 inpatient, 31 aftercare, and 57 general high school students)
      aged 13 to 18. Findings suggest that inpatient, chemically dependent adolescents
      have lower self-esteem than the other two groups. For the chemically dependent
      adolescent, nursing case management with communication among and between health
      care providers, school professionals, and family may facilitate successful, long
      term recovery. For adolescents at risk for development of chemical dependence,
      nursing health promotion behaviors, such as early assessment and implementation
      of self-esteem-building activities, may assist in prevention of chemical
      dependency.

PMID- 7633339
TI  - A nursing survey to determine the characteristics of medication administration
      through enteral feeding catheters.
AB  - A statewide survey was designed to develop a better understanding of the current
      practices and problems encountered with medication administration through enteral
      feeding catheters (EFCs). The sample of 223 registered nurses and licensed
      practical nurses estimated that a median of 10% of patients received medications
      through an EFC. EFC obstruction was estimated to have occurred a median of 1.5
      times per week, with 50% of obstructions estimated to be due to medication
      administration. Nine of 14 specific medications reported as "most frequently
      contributing to" feeding catheter obstruction available in liquid form, yet
      tablets were crushed and given. When nurses perceived the pharmacy department as
      helping them insure that liquid dosage form was used, there was greater use of
      liquid forms, less use of crushed forms, and less medication-associated catheter
      obstruction. In this sample, the majority of nurses did not follow consistently
      the few recommendations available.

PMID- 7633340
TI  - Fruitlax: management of constipation in children with disabilities.
AB  - Seven children, with a variety of disabilities, who had experienced chronic
      constipation, participated in a study of the use of Fruitlax, a natural laxative.
      Using an AB single-subject design, data were collected for each child for a
      baseline period A (2 weeks) and for an intervention period B (minimum of 3
      weeks), which included the addition of Fruitlax to the subjects' diets. Whereas
      each child experienced some change in bowel pattern (consistency, effort required
      to have a bowel movement, color, amount, frequency, and number of bowel movements
      per day), the particular change was different for each child. Fruitlax does
      appear to be a useful natural laxative for some children; however, additional
      research with a larger sample is required. The Glenrose Stool Consistency Tool
      was developed for use in this study. Further work is needed in the use of the
      tool by clients, their families, and health care workers.

PMID- 7633341
TI  - Coprolite assessment in nursing research and practice.
AB  - A reliable assessment of stools without the use of metabolic assays of stool
      content has not previously existed. The Wanger Stool Assessment Instrument (WSAI)
      was initially conceived as an efficacy outcome measure for a clinical
      investigation of enteral feedings. The WSAI is a descriptive tool that has three
      scales: a seven-category color scale, an ordinal scale that describes amount, and
      an ordinal scale that ranks consistency of stools. Instrument testing and
      development were conducted in stages. Nursing staff using the instrument reported
      that its use improved data collection as well as the patient information
      communicated among health care staff.

PMID- 7633342
TI  - Hmong cultural practices and beliefs: the postpartum period.
AB  - The purpose of this study was to explore the cultural practices and beliefs of
      the Hmong in the postpartum period. Using the qualitative research method of in
      depth interviewing, data were collected through semistructured interviews. A
      convenience sample of 52 childbearing Hmong women was interviewed with the help
      of Hmong interpreters. The interviews were audiotaped and transcribed for
      analysis. Data analysis revealed cultural practices and beliefs categories
      related to diet, rest period, appropriate clothing, breast feeding, and sex
      practices in the postpartum period. Implications for nursing include both
      cultural sensitivity and an understanding of such traditional practices, before
      suggesting or implementing any health-promotion activities.

PMID- 7633343
TI  - Anesthetic drug interactions.

PMID- 7633344
TI  - Evolution of safety in anesthesia.
AB  - The evolution of anesthesia safety has paralleled the evolution of anesthesia
      over the last several hundred years. This article describes the introduction of
      safer practices of anesthesia and the impetus for these changes in practice that
      improved patient safety. It discusses both the role of technology in the
      advancement of safety and the policies developed by professional organizations of
      anesthesia care providers.

PMID- 7633345
TI  - Informed consent: an essential element of safe anesthesia practice.
AB  - Generally, health care providers have viewed safety in terms of prevention of
      patient accidents. However, with the growth of patient consumerism and stress on
      quality improvement, the concept of "safety" has been expanded. This article
      examines the legal concept of informed consent and offers practical suggestions
      on increasing both patient and provider safety and improving quality of care. For
      reasons dictated by statute, case law, and professional ethics, informed consent
      should be part of the practice of every CRNA. With proper informed consent,
      misinformation, dissatisfaction, and subsequent legal action can be diminished.
      Information should be offered to the patient and family and reinforced with
      written educational materials and instructions. These procedures should be
      documented in the medical record to provide verification that the patient was
      informed of the risks and benefits and agreed to the procedure contemplated.
      Failure to do so could expose the CRNA to legal actions under legal theories that
      include not only negligence, but battery, and contract as well.

PMID- 7633346
TI  - Regional anesthesia: is it safer?
AB  - This article provides an overview of the current status of general anesthesia and
      regional anesthesia techniques including complications occurring after using
      these techniques. The advantages, disadvantages, mortality, and morbidity are
      described for these two techniques.

PMID- 7633347
TI  - Orotracheal tube intracuff pressure initially and during anesthesia including
      nitrous oxide.
AB  - Certified Registered Nurse Anesthetists (CRNA) have an ethical obligation to
      assure the safety of the anesthetized patient. Maintenance of orotracheal tube
      intra-cuff pressure (IcP) in a range preventing aspiration and avoiding tracheal
      ischemia is one way to enhance patient safety. Currently, no standardized method
      of cuff inflation and IcP maintenance is used in anesthesia practice. In
      addition, nitrous oxide (N2O) has the ability to diffuse into and inflate a cuff.
      Rate of N2O induced cuff inflation in vivo, has not been clearly delineated in
      the current literature. This study measured IcP initially, and over time during
      an anesthetic including 50% to 70% N2O. The sample consisted of 44 adult subjects
      intubated orally. Cuff inflation technique was identified and initial IcPs were
      recorded. IcP was then adjusted to 19 mm Hg and was continuously monitored until
      increasing to 25 mm Hg. A variety of cuff inflation methods were observed none of
      which consistently achieved an initial IcP within the target range of 19 to 25 mm
      Hg. IcP rose from 19 to 25 mm Hg in all cases during N2O administration. Elapsed
      time for the IcP increase ranged from 2 to 52 minutes (mean = 12.34, median = 8
      minutes). During anesthesia with 50% to 70% N2O, IcP will increase from initial
      safe levels to ischemia producing levels. Devices and approaches designed to
      limit N2O induced IcP increase have been described, however only direct IcP
      monitoring has been shown to assure safe initial and ongoing IcP.

PMID- 7633348
TI  - The safe use of disposable syringes in anesthesia: cost effective or costly?
AB  - Many anesthesia practitioners reuse disposable syringes and multidose drug vials
      from case to case despite the known hazards of blood-borne disease transmission.
      This practice may be hazardous to both patients and practitioners. Microscopic
      amounts of blood in the intravenous tubing can cause contamination of syringes,
      needles, and drug vials. Contaminated multidose vials have been associated with
      the transmission of both hepatitis B and bacterial infections. This article
      examines the potential risks of contamination from the reuse of disposable
      syringes and the myth about the cost savings of this practice.

PMID- 7633349
TI  - The safe practice of anesthesia in developing countries.
AB  - Nurse anesthetists providing services in developing countries must be aware of
      the hazards inherent in such a mission. Proper planning and preparation are
      essential to insure safe, quality anesthesia care. Working conditions are
      austere; electrical supplies may be erratic, oxygen sources inconsistent, and up
      to-date monitoring systems nonexistent. Medications and supplies will be limited,
      mandating conservation, reuse, and strict adherence to infection control
      procedures. Safe, reliable anesthesia delivery systems, preferably with the
      ability to scavenge waste anesthetics are required. Patients frequently have
      diseases endemic to the area and language barriers cause confusion and
      misunderstandings. The nurse anesthetist's role in these situations is
      multifaceted. This article describes how the nurse anesthetist must be creative,
      adaptable, and self-reliant to provide a high standard of anesthetic care and
      prevent mishaps in austere environments.

PMID- 7633350
TI  - Vigilance: a concept and a reality.
AB  - Vigilance is a word that is underused in current anesthesia practice. Attention
      is turning from the patient to the machine and monitor. Vigilance has a definite
      role in anesthesia safety and the high technology anesthesia environment only
      enhances the need for vigilance. This article analyzes the concept of vigilance
      and its implication on nurse anesthesia practice.

PMID- 7633351
TI  - Malignant hyperthermia.

PMID- 7633352
TI  - [Mts1 protein in the cytoplasm of metastasizing tumors].

PMID- 7633353
TI  - [Increase in sensitivity of tumor cells to cyclophosphamide as a result of
      exposure to shock waves].

PMID- 7633354
TI  - [Morphometric identification of immunohistochemically stained mammalian brain
      glial cells].

PMID- 7633355
TI  - [Asymmetry of peripheral effects of unilateral intranasal administration of
      oxytocin to male white rats].

PMID- 7633356
TI  - [Change in the equilibrium binding parameters of (3H)-quinuclidinylbenzilate in
      rabbit atrial membranes exposed to lysophosphatidylcholine].

PMID- 7633357
TI  - [Thermal and radiation stability of populations of Lymnaea stagnalis (Gastropoda,
      pulmonata) from bodies of water with various forms of anthropogenic loads].

PMID- 7633358
TI  - [Peripheral bronchial carcinoid: bibliography and case report].

PMID- 7633359
TI  - [Chronic sputum positive tuberculosis--an epidemiologic problem].

PMID- 7633360
TI  - [Patients with chronic sputum positive tuberculosis-a therapeutic problem].

PMID- 7633361
TI  - [Drugs used in systemic fungal infections].

PMID- 7633362
TI  - [Nobel prize in physiology and medicine in the year 1994].

PMID- 7633363
TI  - [Drug resistance in patients with tuberculosis in Poland in the years 1966-1992.
      A test for evaluating the scale of the problem].
AB  - The study analysed the incidence of subjects with tuberculosis who were sputum
      positive and with at least one drug resistance of the bacilli was observed. The
      number of such cases in the total population of sputum positive cases in the
      years 1966-1992. In this period a marked decrease of patients with drug
      resistance was noticed, from 68/100,000 in 1966 to 1.1/100,000 in 1992. The rate
      of decline was observed to be decreasing in the last years. Patients with drug
      resistance comprised 32.5% of all sputum positive patients in 1966 and 4.4% in
      1992. The decrease in the number and the percentage of drug resistant cases was
      observed parallelly to the general trend of better mass chemotherapy efficacy.

PMID- 7633364
TI  - [Characterization of patients with treatment failure in the Central Tuberculosis
      Registry].
AB  - An analysis was carried out in order to explain the reason of treatment failure
      in patients with bacteriology confirmed active tuberculosis registered in the
      Central Tuberculosis Register in the years 1988-1991. The population of patients
      is whom failure of treatment was observed is older compared with the population
      of patients in whom the treatment did not fail. The regimens in both groups were
      similar although the duration of the regimens was shorter in the group in whom
      tuberculosis was not eradicated (less than 3 months or the treatment duration
      could not be established). In the chronic sputum positive patients severer cases
      of tuberculosis were observed more often. Tuberculosis coexistent with other
      diseases was seen twice more often. The result of therapy in patients with
      bacteriologically confirmed tuberculosis can be effected by coexistency of
      tuberculosis and alcoholism.

PMID- 7633365
TI  - [The role of bronchoscopy and bronchoalveolar lavage in diagnosis of pulmonary
      tuberculosis in AIDS].
AB  - Bronchoscopy was carried out in 32 HIV seropositive patients, most with AIDS
      during the period between January 1992 and August 1993. In 14 patients
      tuberculosis was diagnosed, in 13 it was bacteriologically confirmed. The mean
      age of the examined patients was 35.5 years (range 22-49 years). In 50% of the
      BAL samples bacterioscopy was positive. Bacteriological examination of the sputum
      and BAL fluid (bacterioscopy and culture) produced a confirmation of tuberculosis
      in 99.9% of the cases.

PMID- 7633366
TI  - [Incidence of tuberculosis in patients with hematologic malignancies].
AB  - The analysis of the incidence of tuberculosis in patients with hematological
      malignancies was performed in 2,025 patients hospitalized in internal clinic.
      Only in 42 cases tuberculosis was noticed.

PMID- 7633367
TI  - [Occupational exposure and histologic differentiation of lung cancer.
      Retrospective assessment in Cracow].
AB  - A population-based case-control study was performed in Cracow, Poland. Male cases
      and controls were identified from the Cracow Death Register. Information were
      obtained by mailed questionnaire from next-of-kin on smoking, occupational
      branch, occupational exposures and other pertinent variables. Response rates were
      73.5% in cases and 72.0% in controls. For cases that underwent a bronchial biopsy
      or surgical excision the histological diagnosis of the tumor was obtained from
      clinical records. The case group contained 343 subjects with squamous cell
      carcinomas, 151 small cell carcinomas and 106 adenocarcinomas. 27 cases showed
      other histological types (large cell carcinoma and not classifiable). Analysis
      was performed separately by histological type for occupational exposure variables
      adjusted for smoking. Long-term exposure to mineral dust and metal dust (20 years
      or more) was found to be a significant risk factor for small cell and squamous
      cell carcinoma. The effect was more pronounced if the analysis was restricted to
      the age groups "less than 70 years". The highest relative risk due to
      occupational exposures was found for squamous cell carcinoma and mineral dust
      exposure for more than 20 years (RR = 2.45, 95% CI 1.43-4.19). The estimated
      effect of mineral dust on small cell carcinoma and adenocarcinoma was slightly
      lower (RR = 2.29, 95% CI 1.16-4.53 and RR = 2.04, 95% CI 0.89-4.64,
      respectively). The effect of metal dust and fumes appeared to be about the same
      for squamous and small cell carcinoma.

PMID- 7633368
TI  - [Effect of tobacco smoke on serum antioxidant activity].
AB  - Oxidants of cigarette smoke and those released from phagocytes in smoker's lungs
      may inactivate alpha-1-antiproteinase. Thus, the "elastase-antielastase"
      imbalance may lead to lung tissue destruction and emphysema. Insufficient
      antioxidant protection, postulated by some authors might be an additional factor
      contributing to this process. The presented data on the influence of acute in
      vitro exposure to cigarette smoke in humans did not show difference in serum
      antioxidant activity (AOA) before and after the exposure. Attempts were made to
      evaluate the effect of whole cigarette smoke, its gas-phase and water-soluble
      phase on serum AOA in vitro. The results show that gas-phase leads to the
      depletion of serum AOA, whereas water-soluble phase exerts protective effect.
      Thus, at least part of oxidants might be inactivated in the stream of inhaled
      smoke. In conclusion, we doubt that serum AOA is influenced as a result of
      smoking and that the depletion of serum AOA is a decisive factor in the
      development of pulmonary emphysema.

PMID- 7633369
TI  - [Hyperreactivity and immunity in tuberculosis].

PMID- 7633371
TI  - [Use of video-thoracoscopy for diagnostic and small surgical procedures in the
      chest].
AB  - The report introduces videothoracoscopy as a new diagnostic and therapeutical
      method in chest surgery. The main indications for thoracoscopic procedures were
      described. Also, 37 videothoracoscopic procedures performed on 35 patients were
      presented. In 5 cases procedure was therapeutical, in the rest of them
      diagnostic. In all diagnostic cases, thoracoscopic procedures allowed to
      determine accurate diagnosis. No significant complications were observed.

PMID- 7633370
TI  - [Initial experience with a new type of high energy neodymium laser in correcting
      stenosis of the airway].
AB  - The aim of the study was to assess the use of a new Nd:YAG laser--mediLas
      fibertom--in correcting malignant and benign stenoses of the airways. Eighteen
      patients were included in the study. In 9 these were caused by malignant tumors,
      in 3 by nonmalignant tumors, in 6 by post-inflammatory stenoses of the airways.
      Altogether 99 laser sessions were carried out. In patients with malignant
      diseases complete recanalization was achieved in 6 patients, in 2 partial. One
      patients did not benefit form the laser procedure. In patients with benign tumors
      complete recanalization was achieved in all of the patients. In 5 out of 6
      patients the post inflammatory stenosis was corrected. Satisfactory results
      observed after the second, fourth and one year after the initial laser procedure
      encourage to use this from of therapy in cases of malignant and nonmalignant
      narrowing of the airways.

PMID- 7633372
TI  - [A case of bronchial carcinoid diagnosed after 21 years of recurrent lung
      infections].
AB  - A case of 59 year old woman with a 21 year history of recurrent pneumonias of the
      upper left lobe is presented. When she at last agreed for the diagnosis her chest
      X-rays revealed atelectasis and cirrhosis with bronchiectases of the left lung.
      Tumor of the left main bronchus and severe inflammation of the surrounding mucosa
      with purulent secretion were found during bronchofiberoscopy. The patient
      underwent left pneumonectomy. Histological examination of the specimen revealed
      presence of carcinoid in the main left bronchus without involvement of the
      regional lymphnodes, with signs of irreversible damage of other bronchi and
      pulmonary tissue. The very long period of observation since the first symptoms,
      no metastases in the bronchopulmonary lymphonodes and no distant metastases
      indicate the low-grade malignancy of the carcinoid in the presented case.

PMID- 7633373
TI  - [Recurrent atypical bronchial tumor diagnosed as small cell lung cancer].
AB  - The case of atypical carcinoid was presented. 5 years after resection of
      mediastinal mass, the tumor in main left bronchus developed and the diagnosis of
      small cell lung cancer was established. The pathological analysis of previous
      slides from resected tumour and bronchial biopsy showed the same atypical
      carcinoid. The patient was successfully treated using chemotherapy.

PMID- 7633375
TI  - [Diagnosis of Mycobacterium tuberculosis infections using PCR methods].
AB  - This study is the first application of molecular-genetic methods for diagnosis of
      Mycobacterium tuberculosis in Poland. Polymerase chain reaction (PCR) with
      primers targeted to insertion sequence-like element 6110 (IS6110) was used in the
      examination of sputum from 60 patients (30 with tuberculosis and 30 with other
      respiratory tract diseases). Results obtained by PCR were compared to
      microbiological methods (fast-acid staining, culture) and clinical examination.
      We found a 100% specificity of PCR.

PMID- 7633374
TI  - [Lung carcinoids diagnosed as small cell lung cancers--important diagnostic
      problem].
AB  - The four cases of bronchial carcinoids were presented. Based on bronchoscopic
      biopsies the initial diagnosis of small cell lung cancer was established in them.
      The analysis of medical history was strongly suggested for carcinoid but not for
      small cell carcinoma. In each of them thoracotomy was performed and correct
      diagnosis of carcinoid was estimated based on resected tumour. The diagnostic
      criteria for bronchial carcinoid were discussed.

PMID- 7633376
TI  - [Indications for lung transplantation].

PMID- 7633377
TI  - [Transbronchial biopsy of a lung transplant].

PMID- 7633378
TI  - [Directing patients after lung transplantation with regard to complications].

PMID- 7633379
TI  - [Neuroendocrine cells of the respiratory system and neuroendocrine cancers of the
      lung].

PMID- 7633380
TI  - Toxicology; in vivo x-ray fluorescence for the assessment of heavy metal
      concentrations in man.
AB  - x-Ray fluorescence (XRF) analysis and neutron activation analysis (NAA) are the
      two main methods for non-invasive in vivo determination of heavy metal
      concentrations in man. This paper describes various XRF-techniques developed for
      the measurements of cadmium, mercury and lead, primarily in occupationally
      exposed persons. Measurements have revealed cadmium concentrations close to 400
      micrograms/g in the kidneys of exposed workers. Today, the technique can also be
      used for measuring kidney cadmium levels in the general population. Significantly
      different cadmium concentrations between groups of smokers and non-smokers have
      been observed. For workers with current lead exposure, there is no correlation
      between lead in finger bone and lead in blood. However, for retired lead workers,
      there is a relation between these levels, due to the endogenous excretion of lead
      from the skeleton. From a longitudinal study of retired lead workers, the
      biological half-time for bone lead was estimated to about 16 yr. Recently, the
      XRF-technique was shown to be capable of measuring mercury in vivo. On a group of
      chloralkali workers, we found kidney mercury concentrations ranging from non
      detectable to over 50 micrograms/g.

PMID- 7633382
TI  - X-ray fluorescence analysis of Cd and tissue characterization via scattered
      radiation evaluation: a feasibility study for in vivo applications.

PMID- 7633381
TI  - Measurements of radon activity in indoor air in dwellings and enclosed work areas
      in Morocco.

PMID- 7633383
TI  - Radioactivity in foodstuffs in Egypt.

PMID- 7633384
TI  - A feasibility study: in vivo x-ray fluorescence of iron using 109Cd.

PMID- 7633385
TI  - Treatment of data in the study of elemental concentration of biological
      materials.

PMID- 7633386
TI  - Long-term effects of gamma-sterilization on degradation of implant materials.

PMID- 7633387
TI  - Scattering of photons and influence in diagnostic radiology.

PMID- 7633388
TI  - Use of normalised axial distance function in semiempirical calculation of isodose
      curves for 60Co teletherapy.

PMID- 7633389
TI  - Features of the measurement of fat in meat using the neutron/gamma transmission
      (NEUGAT) method.
AB  - Practical requirements for the non-invasive measurement of the composition by
      weight of fat in boneless meat are discussed including taking into account the
      effects of variation in product thickness, and illustrating the importance of the
      dual beam approach in making measurements for production-line meat boxes.
      Insensitivity to the fat distribution and product temperature, and the agreement
      between the theoretical and experimental values of the statistical spread are
      shown. A comparison is made of measurement using an 241Am-Be and a 252Cf source.

PMID- 7633390
TI  - Design of gas targets for the production of medically used radionuclides with the
      help of Monte-Carlo simulation of small angle multiple scattering of charged
      particles.
AB  - Due to scattering of protons or deuterons in the target gas the radius of beams
      increases with increasing penetration depth of the particles. The increase
      depends on the kind of beam particle, the energy, the target gas and its
      temperature and pressure. A Monte-Carlo program was developed for stimulation of
      multiple scattering. The initial beam has a particle distribution of variable
      sinusoidal shape behind the entrance window and may be cut off by the simulation
      of a collimator. The beam distribution is calculated for up to 14 planes
      representing energy values of the particles due to a predefined range from one
      plane to the next. The energy loss is calculated with the help of an integrated
      Bethe-Bloch routine. The distribution of the particles within the plane may be
      rearranged into profiles and transferred to a spreadsheet for further
      manipulation and graphical printout. Simulations are carried out for radionuclide
      production routes, commonly used for position emission tomography (PET).

PMID- 7633391
TI  - [166Dy]dysprosium/[166Ho]holmium in vivo generator.
AB  - A novel approach for the delivery of 166Ho (t1/2 = 26.6 h) to tissue is via the
      in vivo decay of its 81.5 h parent, 166Dy-an in vivo generator system. A critical
      question for the in vivo 166Dy/166Ho generator system is whether translocation of
      the daughter nucleus occurs. The in vitro and in vivo integrity of the
      [166Dy]Dy/166Ho-DTPA complex was investigated and results indicated that no
      translocation of the daughter nucleus occurs subsequent to beta- decay of 166Dy.
      Biodistribution studies of [166Dy]Dy-DTPA showed that the ratio of 166Dy/166Ho in
      bone remains constant (+/- 7%) over a 20 h period, indicating no significant in
      vivo loss of 166Ho from the complex. Increasing the in vivo residence time of
      [166Dy]Dy-DTPA complex attached to HSA gave similar results.

PMID- 7633392
TI  - Synthesis of two radiofluorinated cocaine analogues using distilled 2
      [18F]fluoroethyl bromide.
AB  - Two fluorinated congeners of cocaine, 2'-fluoroethyl (1R-2-exo-3-exo)-8-methyl-3
      (4-methylphenyl)-8-azabicyclo[3.2.1]octane- 2-carboxylate (FETT) and its 4
      chlorophenyl analogue (FECT) were synthesized. Radiolabelling with 18F was
      achieved by O-[18F]fluoroalkylation of the corresponding carboxylic acid salts
      with distilled 2-[18F]fluoroethyl bromide in DMF. After HPLC purification, yields
      of radiochemically pure, formulated products were 22-30% (not corrected for
      decay) in a synthesis time of 60-70 min. The use of distilled 2-[18F]fluoroethyl
      bromide was indispensable for the reliable production of pure products.

PMID- 7633393
TI  - Low energy photon attenuation measurements of hydrophilic materials for tissue
      equivalent phantoms.
AB  - The object of the study was to measure the linear attenuation coefficients of
      hydrophilic materials with the aim of investigating their suitability as tissue
      equivalent materials. Hydrophilic materials are used in the ophthalmic industry
      for the manufacture of soft contact lenses. Hydrophilic materials have the trade
      name "Biogel" and are commonly known as hydrogels. Two types of hydrophilic
      material were tested, ED4C (72% water uptake by weight) and EDIS (60% water
      uptake by weight). The measurements were obtained using gamma-ray photons of
      energy 59.5 keV, and x-ray photons of energies 44.23 and 17.44 keV. Measurements
      were made for material types ED4C and EDIS in both the dry and fully hydrated
      state. Measurements were also made on powdered samples of ED4C at different
      hydration levels using a photon energy of 17.44 keV and powdered samples of EDIS
      at different hydration levels using a photon energy of 59.5 keV. The precision of
      the measurements was approx. 1%. It was found that material ED4C has linear
      attenuation coefficients that closely match those of the calculated values for
      soft tissue across the range of energies used.

PMID- 7633394
TI  - ESR of sugar as a personnel monitor for radiation emergencies.
AB  - In the case of radiation emergency, a sugar method, with readout by electron spin
      resonance analysis as personnel monitor for the affected population, is proposed.
      Critical characteristics of the method are economics, universal availability and
      portability, with superior quantitative monitoring characteristics for ionizing
      radiation and relatively simplicity of the procedure for evaluating dose to
      individuals or to households after irradiation and readout using this widely
      available, compact monitor. The dose linearity of the sugar/ESR monitor is
      experimentally verified from about 3 cGy to 6 x 10(5) cGy and the dose detection
      limit is 0.5 mGy, with the limit of error of about 80% at the confidence level of
      95%. A decrease in the number of the radiation-induced paramagnetic centers (free
      radicals) is not observed for irradiated sugar held at temperature up to 100
      degrees C over about 90 min. It is observed that the free radicals cannot be
      detected from water solutions of the irradiated sugar. The sugar/ESR method is
      proposed as one of the most useful regional personal monitors for major radiation
      emergencies.

PMID- 7633395
TI  - Complex disease genetics gets more complex.

PMID- 7633396
TI  - Regulation of insulin gene expression by the IDDM associated, insulin locus
      haplotype.
AB  - A 4.1 kb genomic region, spanning the insulin (INS) gene, confers genetic
      susceptibility to Type 1 or insulin-dependent diabetes mellitus (IDDM). Ten
      polymorphisms within this region form two predominant, complementary haplotypes.
      We have been studying the effects of these polymorphisms on the levels of insulin
      mRNA. Cloned genomic DNA fragments representing these two separate haplotypes
      were transiently transfected into a rodent pancreatic beta cell line, HIT-T15.
      These studies revealed that insulin mRNA levels were consistently higher in the
      transfectants expressing the diabetic haplotype. Over-expression of insulin mRNA
      may provide the basic mechanism for the diabetic susceptibility encoded at the
      INS locus.

PMID- 7633397
TI  - The D5 dopamine receptor gene in schizophrenia: identification of a nonsense
      change and multiple missense changes but lack of association with disease.
AB  - To determine whether mutations in the D5 dopamine receptor gene (DRD5) are
      associated with schizophrenia, the gene was examined in 78 unrelated
      schizophrenic individuals (156 DRD5 alleles). After amplification by the
      polymerase chain reaction, products were examined by dideoxy fingerprinting
      (ddF), a screening method related to single strand conformational polymorphism
      analysis that detects essentially 100% of mutations. All samples with abnormal
      ddF patterns were sequenced. Nine different sequence changes were identified.
      Five of these were sequence changes that would result in protein alterations; of
      these, one was a nonsense change (C335X), one was a missense change in an amino
      acid conserved in all dopamine receptors (N351D), two were missense changes in
      amino acids that are identical in only some dopamine receptors and in only some
      species (A269V; S453C), and one was a missense change in a non-conserved amino
      acid (P330Q). To investigate whether the nonsense change (C335X), predicted to
      prematurely truncate the receptor protein and result in a 50% diminution of
      functional protein, was associated with schizophrenia, other neuropsychiatric
      diseases, or specific neuropsychological, psychophysiological, or personality
      traits, both case-control and family analyses were performed. No statistically
      significant associations were detected with schizophrenia or other
      neuropsychiatric disease. There also were no significant associations between any
      one measure of neuropsychological function. However, a post-hoc analysis of
      combined measures of frontal lobe function hinted that heterozygotes for C335X
      may have a vulnerability to mild impairment, but these findings must be
      interpreted with caution.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7633398
TI  - Characterization of alternative amino acid substitutions at arginine 830 of the
      androgen receptor that cause complete androgen insensitivity in three families.
AB  - We have studied two different missense mutations at arginine-830 in exon 7 of the
      human androgen receptor (hAR) gene that cause complete androgen insensitivity
      (CAIS) in three families. These substitutions result from point mutations at
      nucleotide 2489: a G-->T transversion causes Arg830Leu and a G-->A transition
      causes Arg830Gln. Genital skin fibroblasts of the patients have negligible
      androgen-binding capacity. The mutations were recreated in an hAR cDNA expression
      vector that was transiently transfected into COS-1 cells. Both mutant androgen
      receptors have increased dissociation rate constants and apparent equilibrium
      rate constants when measured with 5 alpha-dihydrotestosterone or the synthetic,
      nonmetabolizable androgens, mibolerone or methyltrienolone. The mutant androgen
      binding activities share a distinctive thermal misbehavior. At 37 degrees C R830Q
      and R830L are about 40% and 10% of normal, respectively. At 22 degrees C both
      mutants gain androgen binding while the normal decreases by 20%; for R830Q the
      augmented value approaches 60% of the normal. During prolonged 18 h incubation at
      37 degrees C, androgen binding of the normal AR is stable while that of both
      mutants decreases by at least 85%. Both mutants have a very reduced ability to
      transactivate a cotransfected androgen-responsive reporter gene, but R830Q is
      better than R830L. We conclude that arginine-830 is important for A-R complex
      stability, and that its replacement by glutamine or leucine yields distinctive
      functional aberrations.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7633399
TI  - Evidence for a repressive function of the long polyglutamine tract in the human
      androgen receptor: possible pathogenetic relevance for the (CAG)n-expanded
      neuronopathies.
AB  - We have reported that polyglutamine (polyGln)-expanded human androgen receptors
      (hAR) have reduced transactivational competence in transfected cells. We presumed
      that maximal hAR transactivation requires a normal-size polyGln tract. Here we
      report, however, that hAR transactivity and polyGln-tract length are related
      inversely: n = 0 > 12 > 20 > 40 > 50. Thus, a normal-size polyGln tract represses
      the transactivational competence of a polyGln-free hAR, and polyGln expansion
      increases that negative effect. This observation has pathogenetic implications
      for X-linked spinobular muscular atrophy (Kennedy syndrome), and possibly for the
      autosomal dominant central neuronopathies associated with (CAG)n expansion in the
      translated portion of four different genes.

PMID- 7633400
TI  - Ultra-sensitive FISH using peroxidase-mediated deposition of biotin- or
      fluorochrome tyramides.
AB  - We describe a detection principle for indirect fluorescence in situ hybridization
      (FISH) methods that with only one or two antibody layers dramatically improves
      FISH signal intensities. The method uses as a first layer an anti-hapten
      immunoglobulin [or (strept)avidin] conjugated to peroxidase. The quintessence of
      the method is the use of fluorochrome- or biotin labelled tyramides as peroxidase
      substrates to generate and deposit many fluorochrome or biotin molecules close to
      the in situ bound peroxidase. These may either be directly evaluated under the
      fluorescence microscope or after another incubation with fluorochrome-labelled
      (strept)avidin.

PMID- 7633401
TI  - Evidence for two tumour suppressor loci on chromosomal bands 1p35-36 involved in
      neuroblastoma: one probably imprinted, another associated with N-myc
      amplification.
AB  - Previous reports on possible genomic imprinting of the neuroblastoma tumour
      suppressor gene on chromosome 1p36 have been conflicting. Here we report on the
      parental origin of 1p36 alleles lost in 47 neuroblastomas and on a detailed
      Southern blot analysis of the extent of the 1p deletions in 38 cases. The results
      are remarkably different for tumours with and without N-myc amplification. In the
      N-myc single copy tumours we show that the lost 1p36 alleles are of preferential
      maternal origin (16 of 17 cases) and that the commonly deleted region maps to
      1p36.2-3. In contrast, all N-myc amplified neuroblastomas have larger 1p
      deletions, extending from the telomere to at least 1p35-36.1. These deletions are
      of random parental origin (18 of 30 maternal LOH). This strongly suggests that
      different suppressor genes on 1p are inactivated in these two types of
      neuroblastoma. Deletion of a more proximal suppressor gene is associated with N
      myc amplification, while a distal, probably imprinted, suppressor can be deleted
      in N-myc single copy cases.

PMID- 7633402
TI  - Isolation and characterization of a novel gene deleted in DiGeorge syndrome.
AB  - The region commonly deleted in DiGeorge syndrome (DGS) has been localized at
      22q11.1-q11.2 with the aid of a high resolution banding technique. A 22q11
      specific plasmid library was constructed with a microdissection and microcloning
      method. Dosage analysis proved three of 144 randomly selected microclones to
      detect hemizygosity in two patients with DGS. Two of the clones were found to
      contain independent low-copy-number repetitive sequences, all of which were
      included in the region deleted in the DGS patients. Screening of the cosmid
      library and subsequent cosmid walking allowed us to obtain two cosmid contigs
      corresponding to the microclones within the deletion (contig 1 and contig 2),
      whose order fluorescence in situ hybridization identified as centromere-contig 1
      contig 2-telomere on 22q. By direct selection strategy using one of the cosmids
      of contig 1, a 4.3 kb cDNA was obtained from fetal brain cDNA library. Sequence
      analysis of the cDNA revealed an open reading frame encoding 552 amino acids
      which had several characteristics of DNA-binding proteins. The gene, designated
      LZTR-1, which was transcribed in several essential fetal organs, proved to be
      hemizygously deleted in seven of eight DGS patients or its variants, but not in
      one DGS patient and GM00980. Although LZTR-1 does not locate in the shortest
      region of overlap, several of its structural characteristics identifying it as
      transcriptional regulator suggest that it plays a crucial role in embryogenesis
      and that haploinsufficiency of this gene may be partly related to the development
      of DGS.

PMID- 7633403
TI  - Cloning of a balanced translocation breakpoint in the DiGeorge syndrome critical
      region and isolation of a novel potential adhesion receptor gene in its vicinity.
AB  - Deletions of the 22q11.2 have been associated with a wide range of developmental
      defects (notably DiGeorge syndrome, velocardiofacial syndrome, conotruncal
      anomaly face syndrome and isolated conotruncal cardiac defects) classified under
      the acronym CATCH 22. A DiGeorge syndrome patient bearing a balanced
      translocation whose breakpoint maps within the critical region has been
      previously described. We report the construction of a cosmid contig spanning the
      translocation breakpoint and the isolation of a gene mapping 10 kb telomeric to
      the breakpoint. This gene encodes a novel putative adhesion receptor protein,
      which could play a role in neural crest cells migration, a process which has been
      proposed to be altered in DiGeorge syndrome.

PMID- 7633404
TI  - Characterization of the human homologue of the mouse Tg737 candidate polycystic
      kidney disease gene.
AB  - We previously identified a gene from the mutant locus in a new mouse mutation
      that causes recessive polycystic kidney disease. Here we describe the cloning,
      characterization and mapping of the homologous human gene. The human and mouse
      genes are 95% identical at the predicted amino acid sequence level, and both
      genes encode a putative protein that contains a tetratricopeptide repeat motif.
      The human gene, called hTg737, is expressed with a broad tissue distribution that
      includes the the kidney and liver, and gives rise to a 2.9 kb mRNA. The gene
      contains 26 exons and spans a genomic region greater than 100 kb. Chromosome
      mapping experiments revealed that the hTg737 gene maps near the centromere on the
      long arm of human chromosome 13, at position 13q12.1. While this gene does not
      map to the primary locus that has been identified for ARPKD in humans, it may
      represent a candidate gene for other recessive renal disorders that have yet to
      be mapped.

PMID- 7633405
TI  - Splicing mutations of the polycystic kidney disease 1 (PKD1) gene induced by
      intronic deletion.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic disease
      which frequently results in renal failure. The major ADPKD gene, polycystic
      kidney disease 1 (PKD1), has recently been identified. In an attempt to
      understand better the aetiology of this disorder we have searched for mutations
      in the PKD1 gene. Analysis of three regions in the 3' part of the gene has
      revealed two mutations that occur by a novel mechanism. Both mutations are
      deletions (of 18 or 20 bp) within the same 75 bp intron and although these
      deletions do not disrupt the splice donor or acceptor sites at the boundary of
      the intron, they nevertheless result in aberrant splicing. Two different
      transcripts are produced in each case; one includes the deleted intron while the
      other has a 66 bp deletion due to activation of a cryptic 5' splice site. No
      normal product is generated from the deleted gene. Aberrant splicing probably
      occurs because the deleted intron is too small for spliceosome assembly using the
      authentic splice sites; this mechanism has previously only been described from in
      vitro studies of vertebrate genes. A 9 bp direct repeat has been identified
      within the intron, which probably facilitated deletion by promoting misalignment
      of sequence. The possible phenotypic implications of producing more than one
      aberrant PKD1 transcript in these cases are discussed.

PMID- 7633406
TI  - Analysis of the genomic sequence for the autosomal dominant polycystic kidney
      disease (PKD1) gene predicts the presence of a leucine-rich repeat. The American
      PKD1 Consortium (APKD1 Consortium).
AB  - The complete genomic sequence of the gene responsible for the predominant form of
      polycystic kidney disease, PKD1, was determined to provide a framework for
      understanding the biology and evolution of the gene, and to aid in the
      development of molecular diagnostics. The DNA sequence of a 54 kb interval
      immediately upstream of the poly(A) addition signal sequence of the PKD1
      transcript was determined, and then analyzed using computer methods. A leucine
      rich repeat (LRR) motif was identified within the resulting predicted protein
      sequence of the PKD1 gene. By analogy with other LRR-containing proteins, this
      may explain some of the disease-related renal alterations such as mislocalization
      of membrane protein constituents and changes in the extracellular matrix
      organization. Finally, comparison of the genomic sequence and the published
      partial cDNA sequence showed several differences between the two sequences. The
      most significant difference detected predicts a novel carboxy-terminus for the
      PKD1 gene product.

PMID- 7633407
TI  - Uniparental disomy 7 in Silver-Russell syndrome and primordial growth
      retardation.
AB  - Maternal uniparental disomy for the entire chromosome 7 has so far been reported
      in three patients with intrauterine and postnatal growth retardation. Two were
      detected because they were homozygous for a cystic fibrosis mutation for which
      only the mother was heterozygous, and one because he was homozygous for a rare
      COL1A2 mutation. We investigated 35 patients with either the Silver-Russell
      syndrome or primordial growth retardation and their parents with PCR markers to
      search for uniparental disomy 7. Four of 35 patients were found to have maternal
      disomy, including three with isodisomy and one with heterodisomy. The data
      confirm the hypothetical localization of a maternally imprinted gene (or more
      than one such gene) on chromosome 7. It is suggested to search for UPD 7 in
      families with an offspring with sporadic Silver-Russell syndrome or primordial
      growth retardation.

PMID- 7633409
TI  - Recurrent mis-splicing of fibrillin exon 32 in two patients with neonatal Marfan
      syndrome.
AB  - The Marfan syndrome (MFS) is an autosomal dominant heritable disorder of
      connective tissue. Variable and pleiotropic clinical features are observed in the
      skeletal, ocular, and cardiovascular systems. The most severe end of the
      phenotypic spectrum of this disorder comprises a group of patients usually
      diagnosed at birth, who have a life expectancy of little more than a year. To
      distinguish this group of patients from those with classical MFS, we refer to
      them as neonatal Marfan syndrome (nMFS). These infants usually die of congestive
      heart failure rather than aortic aneurysmal disease, the most frequent cause of
      morbidity and mortality in classical MFS. Defects in fibrillin, an elastin
      associated microfibrillar glycoprotein, are now known to cause both the classical
      and neonatal forms of MFS. Here we report the recurrent mis-splicing of fibrillin
      (FBN1) exon 32, a precursor EGF-like calcium binding domain, in two unrelated
      infants with nMFS. The mis-splicing, in one patient, was due to an A-->T
      transversion at the -2 position of the consensus acceptor splice site; while that
      in the second patient was caused by a G-->A transition at the +1 position of the
      donor splice site. Characterization of FBN1 mutations in individuals at the most
      severe end of the Marfan syndrome spectrum should provide greater understanding
      of the multiple domains and regions of fibrillin.

PMID- 7633408
TI  - The gene for a human microfibril-associated glycoprotein is commonly deleted in
      Smith-Magenis syndrome patients.
AB  - Smith-Magenis syndrome (SMS) is a clinically recognizable multiple congenital
      anomaly/mental retardation syndrome associated with deletion of chromosome
      17p11.2. Here we report the identification of a novel gene encoding a human
      microfibril-associated glycoprotein (MFAP4), which has been mapped to the SMS
      region. A full-length cDNA corresponding to this gene has been sequenced, and
      reveals a coding region of 255 amino acids. MFAP4 has a fibrinogen-like domain
      and shares a high level of sequence homology to a fragment of a bovine 36 kDa
      microfibril-associated glycoprotein. The N-terminus of the protein bears an Arg
      Gly-Asp sequence that serves as the ligand motif for cell surface receptor
      integrin. These structural features of MFAP4 suggest that it is an extracellular
      matrix protein involved in cell adhesion or intercellular interactions. Deletion
      analysis has been conducted on 31 SMS patients by polymerase chain reaction and
      Southern analysis of somatic cell hybrids retaining the del(17)(p11.2) chromosome
      or by fluorescence in situ hybridization. The MFAP4 locus is deleted in 30 of 31
      SMS patients. Thus, the function of this gene must be considered in the
      pathogenesis of SMS. Given our previous hypothesis that SMS is a contiguous gene
      syndrome, complete and exhaustive definition of the critical deletion interval
      and a thorough phenotype-genotype correlation is required to demonstrate the role
      and importance of the MFAP4 gene in SMS.

PMID- 7633410
TI  - Inversion of the IDS gene resulting from recombination with IDS-related sequences
      is a common cause of the Hunter syndrome.
AB  - We have recently described the identification of a second IDS locus (IDS-2)
      located within 90 kb telomeric of the IDS gene (Bondeson et al. submitted). Here,
      we show that this region is involved in a recombination event with the IDS gene
      in about 13% of patients with the Hunter syndrome. Analysis of the resulting
      rearrangement at the molecular level showed that these patients have suffered a
      recombination event that results in a disruption of the IDS gene in intron 7 with
      an inversion of the intervening DNA. Interestingly, all of the six cases with a
      similar type of rearrangement showed recombination between intron 7 of the IDS
      gene and sequences close to exon 3 at the IDS-2 locus implying that these regions
      are hot spots for recombination. Analysis by nucleotide sequencing showed that
      the inversion is caused by recombination between homologous sequences present in
      the IDS gene and the IDS-2 locus. No detectable deletions or insertions were
      observed as a result of the recombination event. The results in this study have
      practical implications for diagnosis of the Hunter syndrome.

PMID- 7633411
TI  - Hyperhomocysteinemia in premature arterial disease: examination of cystathionine
      beta-synthase alleles at the molecular level.
AB  - Hyperhomocysteinemia occurs in approximately 30% of the patients with premature
      occlusive arterial disease (POAD). Some of these exhibit significantly reduced
      fibroblast cystathionine beta-synthase (CBS) activities, suggesting that they may
      be heterozygous for CBS deficiency. To test this possibility, we studied cDNA
      derived from four well characterized patients with POAD, exhibiting
      hyperhomocysteinemia and reduced CBS activities, from four normal controls, and
      from four obligatory heterozygotes for CBS deficiency. Lysates of individual
      colonies of E.coli, containing full-length PCR-amplification products in the
      expression vector, pKK388.1, were tested for CBS activity. cDNA from at least
      seven of the eight possible independent POAD alleles encoded catalytically
      active, stable CBS which exhibited normal response to both PLP and AdoMet. The
      sequences of all 3'-untranslated regions of all seven isolated POAD alleles were
      identical to the normal, 'wild-type' CBS sequences. The results of the expression
      studies were confirmed for one POAD patient by determining the full-length cDNA
      sequences for both alleles; these were entirely normal over the complete length
      of the cDNA. In contrast, the screening method correctly distinguished mutant
      from normal alleles in all four obligatory heterozygotes studied. We conclude
      that CBS mRNAs from POAD individuals are free from inactivating mutations,
      including all 33 previously identified in heterozygous carriers and
      homocystinuric patients.

PMID- 7633412
TI  - Deletions in the survival motor neuron gene on 5q13 in autosomal recessive spinal
      muscular atrophy.
AB  - Autosomal recessive spinal muscular atrophy is a motor neuron disease which
      affects about 1 in 10,000 births. Recent evidence shows that the candidate region
      contains multiple copies of genes and pseudogenes and is characterised by genome
      instability. We have analysed the frequency of deletions in a recently
      characterised candidate survival motor neuron (SMN) gene. Our data confirm
      previous analyses and show that this gene is disrupted by deletion in SMA
      patients. The same deletion frequency is observed in the milder variants of the
      disease as in patients with the severe form. In addition, we observed one case of
      a new mutation in a family previously thought not to be segregating for a
      chromosome 5 linked form of SMA. This assay is a very good diagnostic for SMA
      although no direct correlation between phenotype and genotype is apparent and
      carrier status cannot be determined. The implications for the identification of
      the gene or genes causing the disease are discussed.

PMID- 7633413
TI  - Molecular characterization of the human gene encoding an abundant 61 kDa protein
      specific to the retinal pigment epithelium.
AB  - The retinal pigment epithelium (RPE) of the eye expresses an abundant 61 kDa
      protein (RPE65), that is developmentally regulated and tissue-specific. In our
      efforts toward understanding the specialized functions and development of the
      RPE, and the origins of inherited retinal degenerations, we have characterized
      the human gene encoding the 61 kDa protein. This is the first structural
      characterization of a gene transcribed specifically in the RPE. The gene maps to
      human chromosome 1p31. The sequence encoding the transcript spans over 20 kb, and
      is interrupted by 13 introns. A putative transcription start site lies 54 bp
      upstream of the initiation codon. A single transcript of approximately 2.9 kb is
      present in human RPE, and is not detected in other tissues. The deduced 533 amino
      acid sequence of the human protein is 98.7% identical to the bovine, but shows no
      significant similarity to any other entry in the databases. Expression of the 61
      kDa protein appears to depend on the presence of environmental cues, since the
      corresponding transcripts are rapidly lost from RPE cells established in culture.
      Down regulation may occur post-transcriptionally, since AU-rich elements proposed
      to target RNA for rapid degradation are present throughout the 3'-untranslated
      region. The tissue-specific expression, high abundance, evolutionary
      conservation, developmental regulation, and sequence of the 3'-untranslated
      region suggest that the 61 kDa protein is the product of a functionally important
      gene whose expression is tightly regulated.

PMID- 7633414
TI  - Four novel mutations in mucopolysaccharidosis type VII including a unique base
      substitution in exon 10 of the beta-glucuronidase gene that creates a novel 5'
      splice site.
AB  - Mucopolysaccharidosis type VII (MPS VII), or Sly syndrome, is a lysosomal storage
      disorder caused by a deficiency in the enzyme beta-glucuronidase. Various
      clinical phenotypes of this autosomal recessively inherited disease have been
      described. Recent isolation and characterization of human beta-glucuronidase cDNA
      and the genomic sequences facilitate analysis of molecular defects underlying the
      different phenotypes, and eight mutations in the beta-glucuronidase gene have
      been described. This report summarizes studies characterizing four new mutations
      in two Caucasian patients with a severe form of MPS VII. Three are point
      mutations, resulting in two missense and one nonsense change, and one is a 38 bp
      deletion. The first patient was a compound heterozygote having P148S and Y495C
      alleles. The second patient was a compound heterozygote of W507X and a 38 bp
      deletion at position 1642-1679 in exon 10(1642 delta 38nt). The 38 bp deletion
      was caused by a single base change mutation in exon 10 that generates a new,
      premature 5' splice site. Expression of mutant cDNAs encoding each of the four
      mutations showed that all four resulted in a severe reduction of beta
      glucuronidase activity, indicating that these mutations are responsible for the
      reduced enzyme activity in patient cells. These four previously undescribed
      mutations provide further evidence for the broad molecular heterogeneity in Sly
      syndrome.

PMID- 7633415
TI  - Somatic mosaicism of CAG repeat in dentatorubral-pallidoluysian atrophy (DRPLA).
AB  - An unstable expansion of CAG repeat in the coding region of the DRPLA gene on
      chromosome 12p is the mutation specific for hereditary dentatorubral
      pallidoluysian atrophy (DRPLA). We studied the CAG expansion in brain and other
      tissues from six unrelated DRPLA patients. The CAG repeat lengths showed distinct
      differences between tissues. The sizes of the CAG expansion in various regions of
      the brain except the cerebellum were generally larger by several repeats than in
      other peripheral tissues. Brain samples showed greater variation of the expansion
      compared with other tissues, but neither the size of the CAG expansion nor the
      degree of CAG repeat variation parallels the detailed findings of
      neuropathological involvement. We conclude that somatic instabilities of the CAG
      repeat cause tissue variability of the CAG repeat size in DRPLA but other region
      or cell type-specific factors would be involved to explain the selectivity of
      cell damage in DRPLA.

PMID- 7633416
TI  - Identification of a novel phospholipase C family gene at chromosome 2q33 that is
      homozygously deleted in human small cell lung carcinoma.
AB  - Since a considerably high incidence of allelic loss on chromosome 2q was detected
      in lung carcinoma and a homozygous deletion at chromosome 2q33 was detected in a
      small cell lung carcinoma cell line, NCI-H82, a novel tumor suppressor gene has
      been suggested to be present in this chromosomal region. In the present study, we
      constructed a cosmid contig map covering the homozygous deleted region, which was
      estimated as being 220 kbp in size, and identified a gene from the deleted
      region. All of the coding exons of this gene were homozygously deleted in this
      cell line, while a 5'-non-coding exons was retained. Since the gene encodes a
      protein with striking similarity to several members of a family of phospholipase
      C, we designated this gene as PLC-L (phospholipase C-deleted in lung carcinoma).
      The PLC-L gene was expressed in a variety of fetal and adult organs including the
      lung. However, its expression was greatly reduced in seven of 13 (53.8%) of small
      cell lung carcinoma and 13 of 15 (86.7%) of non-small cell lung carcinoma cell
      lines. Since its homology to phospholipase C genes suggests the involvement of
      the PLC-L gene in inositol phospholipid-based intracellular signaling cascade, it
      is possible that aberrant expression of the PLC-L gene contributes to the genesis
      or progression of human lung carcinoma.

PMID- 7633417
TI  - Splice-mediated insertion of an Alu sequence in the COL4A3 mRNA causing autosomal
      recessive Alport syndrome.
AB  - Alport syndrome is a mainly X-linked hereditary disease of basement membranes
      characterized by progressive renal failure, deafness, and ocular lesions. The
      alpha 3(IV) and alpha 4(IV) collagen genes have been recently shown to be
      involved in the less frequent autosomal recessive form. When screening lymphocyte
      COL4A3 mRNAs from Alport patients, we found a mutant whose transcripts were
      disrupted by a 74 bp insertion at the junction of exons IV or V and VI. The
      insertion derives from an antisense Alu element in COL4A3 intron V, which has
      been spliced into the alpha 3(IV) mRNA due to a G to T transversion activating a
      cryptic acceptor splice site in this Alu element. There is complete segregation
      of this mutation with the disease in the family. Our findings provide the first
      evidence for the pathogenic role of abnormal splicing of COL4A3. Moreover, we
      demonstrate the superiority of mutation screening at the mRNA level to detect a
      hitherto poorly recognized mutation mechanism in humans, splice-mediated
      insertion of an Alu fragment into a coding sequence.

PMID- 7633418
TI  - Localization of craniosynostosis Adelaide type to 4p16.
AB  - Craniosynostosis Adelaide type is a rare autosomal dominant syndrome associated
      with digital abnormalities. Linkage mapping was carried out excluding allelism to
      Saethre-Chotzen syndrome at 7p21, craniosynostosis Boston type at 5q34-q35,
      Jackson-Weiss and Crouzon syndromes at 10q24-q25 and Pfeiffer syndrome mapping
      near 8cen. Exclusion mapping was extended to the entire genome until linkage to
      chromosome 4 was detected. A maximum two-point lod score of 6.2 (theta = 0.0) was
      obtained with D4S412. The gene responsible for craniosynostosis Adelaide type was
      localized to 4p16, telomeric to D4S394. This region contains two plausible
      candidate genes, the MSX1 (HOX7) homeobox gene and the FGFR3 fibroblast growth
      factor receptor gene.

PMID- 7633419
TI  - Rapid isolation and characterization of 118 novel C2H2-type zinc finger cDNAs
      expressed in human brain.
AB  - C2H2-type zinc finger genes comprise one of the largest gene families in the
      human genome. These proteins are involved in genetic regulation and development
      and are quite conserved throughout evolution. The finger domains commonly contain
      the small linker peptide TGEKP between some finger units. Here, we report the
      isolation of 133 human zinc finger cDNAs, of which 118 are novel. These clones
      were isolated from human brain cDNA libraries using oligonucleotide hybridization
      followed by expressed sequence tag (EST) analysis, sequencing from the conserved
      linker region using degenerate oligonucleotide primers. This directed partial
      sequencing approach to cDNA isolation and characterization, signature sequencing,
      combines the speed of EST automatic sequencing with the focus of specific cDNA
      family analysis. Signature sequencing minimizes the generation of less
      informative random EST sequences and provides a unique relative position for
      sequence comparison. We also show that there is an even distribution of these
      RNAs from this brain cDNA library, and that these cDNAs contain N-terminal
      domains found in other zinc finger genes. This rapid focused sequencing approach
      should be applicable to any family of cDNAs containing short conserved signature
      peptide sequences.

PMID- 7633420
TI  - Identification of Btk mutations in 20 unrelated patients with X-linked
      agammaglobulinaemia (XLA).
AB  - X-linked agammaglobulinaemia (XLA) is an inherited immunodeficiency resulting
      from mutations in the gene for a cytoplasmic protein tyrosine kinase (Btk). We
      have utilised reverse-transcription-based PCR in combination with the chemical
      cleavage and mismatch technique (CCM) to screen for Btk mutations in 42 unrelated
      patients having classical XLA or 'leaky' XLA-like phenotypes. A variety of
      mutations, including point mutations, large deletions and splicing defects were
      detected using this strategy. In total, 20 mutations were found in these
      patients. All the mutations were different with the exception of three unrelated
      patients who all showed the same Arg-->His amino acid substitution (R641H) at a
      highly-conserved residue in the kinase domain. We have also used structural
      modelling of the Btk kinase domain to predict how two different amino acid
      substitution mutations at highly-conserved residues are likely to affect the Btk
      kinase activity.

PMID- 7633421
TI  - Isolation and characterization of a candidate gene for progressive myoclonus
      epilepsy on 21q22.3.
AB  - The Unverricht-Lundborg type of progressive myoclonus epilepsy (EPM1) and
      autoimmune polyglandular disease type I (APECED) have been mapped to human
      chromosome 21q22.3 by genetic linkage analysis and/or linkage disequilibrium
      studies. In order to isolate the genes for these disorders, we have constructed
      BAC contigs in this region and a 14 week trisomy 21 fetal brain cDNA library. A
      direct cDNA selection technique, modified to permit the recovery 5' and 3' ends
      of cDNA, was applied to gene identification using the BAC contigs. We have
      isolated and characterized a novel gene defined by three overlapping but distinct
      cDNAs of 5, 3, and 3 kb in size all named EHOC-1 (Epilepsy, HOloprosencephaly
      Candidate-1). This gene maps less than 45 kb centromeric of D21S25, and spans at
      least 56 kb of genomic DNA. Northern analysis of the 5 kb cDNA revealed that 8,
      7.5 and 5.3 kb transcripts are ubiquitously expressed in adult tissues. DNA
      sequence analysis of the 5 kb cDNA showed a complete coding sequence of 3570 bp
      that has multiple putative transmembrane domains and has partial homologies to
      transmembrane proteins including sodium channel proteins. This gene (EHOC-1) is a
      good candidate for APECED, and particularly for EPM1 because of the location,
      size, structure and homologies.

PMID- 7633422
TI  - A primary expression map of the chromosome 15q15 region containing the recessive
      form of limb-girdle muscular dystrophy (LGMD2A) gene.
AB  - Previous genetic and physical studies of LGMD2A, an autosomal recessive form of
      limb-girdle muscular dystrophy, have led to the establishment of a 10-12 Mb YAC
      contig encompassing the morbid locus. In order to progress toward the
      identification of the gene involved in LGMD2A, a primary transcription map of
      this genomic region was generated. The direct cDNA selection strategy was used
      with three YACs covering the candidate region and two different muscle cDNA
      libraries. Seventeen transcription units were identified among 171 cDNA fragments
      analysed. Five sequences corresponded to known genes, and twelve to new ones.
      They were characterized for their sequences, physical positions within the YAC
      contig, and expression patterns. Among those specifically transcribed in muscle,
      the calpain gene is a good positional and functional candidate for LGMD2A.

PMID- 7633423
TI  - Sequence variability of a prolonged tetranucleotide repeat.
AB  - A tetranucleotide repeat located in intron 20 of the RB gene consists of 16-26
      CTTT(+/- T) repeats in 99% of the alleles. In the remaining 1% of alleles the
      segment is extended to a length of > 60 repeats. Sequence analysis revealed that
      the prolonged alleles either consisted of perfect CTTT(+/- T) repeats or
      irregular repeat sequences with variable combinations of C and T. The data
      provide clues to the mechanisms causing unstable expansions of repeats.

PMID- 7633424
TI  - Three genes that escape X chromosome inactivation are clustered within a 6 Mb YAC
      contig and STS map in Xp11.21-p11.22.
AB  - In order to study the distribution of genes that escape X chromosome
      inactivation, a high density yeast artificial chromosome (YAC) contig and STS map
      spanning approximately 6 Mb has been constructed in Xp11.21-p11.22. The contig
      contains 113 YACs mapped with 53 markers, including 10 genes. Four genes have
      been assayed for their expression status on both the active and inactive human X
      chromosomes, and these data have been combined with previous results on two other
      genes in the contig. Three of these genes escape X inactivation and have been
      localized to a single YAC clone of approximately 1075 kb. The other three genes
      are subject to inactivation, with two of them lying among the genes that escape
      inactivation. These results suggest that there are both regional control signals
      as well as gene-specific elements that determine the X inactivation status of
      genes on the proximal short arm of the human X chromosome.

PMID- 7633425
TI  - Mucopolysaccharidosis type IVA: identification of six novel mutations among non
      Japanese patients.

PMID- 7633426
TI  - A novel missense mutation in the type II 3 beta-hydroxysteroid dehydrogenase gene
      in a family with classical salt-wasting congenital adrenal hyperplasia due to 3
      beta-hydroxysteroid dehydrogenase deficiency.

PMID- 7633428
TI  - Unusual pattern of mitochondrial DNA deletions in skeletal muscle of an adult
      human with chronic fatigue syndrome.

PMID- 7633427
TI  - Medium chain acyl-CoA dehydrogenase deficiency caused by a deletion of exons 11
      and 12.

PMID- 7633431
TI  - Characterisation of a novel splice donor mutation affecting position +1 in intron
      18 of the NF-1 gene.

PMID- 7633430
TI  - Identification of a patient with Bernard-Soulier syndrome and a deletion in the
      DiGeorge/velo-cardio-facial chromosomal region in 22q11.2.

PMID- 7633429
TI  - Mutation analysis in Bruton's tyrosine kinase, the X-linked agammaglobulinaemia
      gene, including identification of an insertional hotspot.

PMID- 7633432
TI  - Two novel factor IX promoter mutations: incremental progress towards 'saturation
      in vivo mutagenesis' of a human promoter region.

PMID- 7633433
TI  - Frame-shift mutation and reduced transcript of p53 gene in a renal cell carcinoma
      cell line, RCC23.

PMID- 7633434
TI  - Rhodopsin mutation proline347-to-alanine in a family with autosomal dominant
      retinitis pigmentosa indicates an important role for proline at position 347.

PMID- 7633435
TI  - A second, large deletion in the HEXB gene in a patient with infantile Sandhoff
      disease.

PMID- 7633436
TI  - A heterogeneous set of FMR1 proteins is widely distributed in mouse tissues and
      is modulated in cell culture.
AB  - The fragile X syndrome is an X-linked inherited disease and is the result of
      transcriptional inactivation of the FMR1 gene and the absence of its encoded FMR
      protein (FMRP). Using a specific monoclonal antibody directed against human FMRP,
      we have studied the steady-state levels of its murine homolog in several tissues
      and organs of adult and young mice. In immunoblot analyses, the antibody
      recognizes a heterogeneous subset of proteins with apparent molecular weights
      ranging from 80 to 70 kDa. These proteins are detected in all the 27 tissues
      tested; however, the relative proportion of each polypeptide recognized varies
      between tissues, and a significantly higher expression is observed in young
      animals. Northern blot analysis of RNA extracted from selected tissues from adult
      mouse shows that these tissues express the major 4.8 kb mRNA, although at
      different levels, and contain several additional shorter transcripts,
      particularly in muscular tissues. We also report that expression of the FMR1 gene
      is modulated in proliferating and quiescent primary mouse kidney cell cultures
      with an inverse relationship between levels of FMR1 mRNA and of its encoded
      proteins. This suggests that FMRPs are highly stable in quiescent cells and that
      FMR1 expression is likely post-transcriptionally controlled. Our results document
      the widespread expression of the FMR1 gene, and suggest that it is controlled by
      different mechanisms implicated in cell growth and differentiation.

PMID- 7633438
TI  - Sex-specific meiotic recombination in the Prader--Willi/Angelman syndrome
      imprinted region.
AB  - Meiotic recombination is a specifically timed and regulated process which does
      not occur randomly throughout the genome, but tends to be clustered in
      'hotspots'. There is extensive evidence that recombination rate is influenced by
      chromatin conformation and that events are primarily initiated at gene promoter
      regions. In an effort to determine the pattern of chromatin condensation and
      recombination at meiosis in an imprinted region, fine scale genetic mapping in
      the approximately 4 Mb Prader-Willi/Angelman syndrome deletion region was
      undertaken. The results indicate that the male-female recombination ratio can
      vary significantly over short regions. A male recombination hotspot is localized
      to between the 3' end of GABRA5 and D15S156, which is adjacent to but outside the
      putative AS/PWS imprinted regions. In addition, a region of relatively high
      recombination in females is observed between D15S128 and D15S97, which spans a
      domain of paternal allele-specific transcription implicated in the Prader-Willi
      syndrome. It is inferred that the inactivation and relative condensation of this
      latter region on the maternal chromosome occurs as a post-meiotic modification.

PMID- 7633439
TI  - Molecular features of the CAG repeats and clinical manifestation of Machado
      Joseph disease.
AB  - Machado--Joseph disease (MJD) is an autosomal dominant spinocerebellar
      degeneration mapped to chromosome 14q32.1. The CAG expansions of the MJD1 gene
      was identified as the cause of the disease. We have analyzed 90 MJD individuals
      from 62 independent MJD families and found that the MJD1 repeat length is
      inversely correlated with the age of onset (r = -0.87). The MJD chromosomes
      contained 61-84 repeat units, whereas normal chromosomes displayed 14-34 repeats.
      In the normal chromosomes, 14 repeat units were the most common and the shortest.
      In association with the clinical anticipation of the disease, a parent--child
      analysis showed the unidirectional expansion of CAG repeats and no case of
      diminution in the affected family. The differences in CAG repeat length between
      parent and child and between siblings are greater in paternal transmission than
      in maternal transmission. Detailed analysis revealed that a large degree of
      expansion was associated with a shorter length of MJD1 gene in paternal
      transmission. On the other hand, the increments of increase were similar for
      shorter and longer expansion in maternal transmission. Among the three clinical
      subtypes, type I of MJD, with dystonia, showed a larger degree of expansion in
      CAG repeats of the gene and younger ages of onset than the other types.

PMID- 7633440
TI  - Reverse replication timing for the XIST gene in human fibroblasts.
AB  - The timing of DNA replication appears to be an important epigenetic regulator of
      gene expression during development. Replication of active genes in expressing
      tissues occurs earlier than does replication of their inactive counterparts in
      nonexpressing tissues. This pattern is also observed for active and inactive
      alleles present in the same cell, as exemplified by genes subject to X chromosome
      inactivation in females. We find that the replication timing of the X-linked XIST
      gene in normal human fibroblasts provides a striking exception to this well
      established pattern. Within the same cell, the expressed allele of XIST
      replicates late in S phase and the silent allele replicates early. This 'reverse'
      replication timing may have functional significance with respect to XIST or could
      be a passive consequence of the replication timing requirements of neighboring
      genes that are subject to X chromosome inactivation. Our finding of early
      replication for XIST in male fibroblasts contrasts with a report of late
      replication in such cells as determined by an in situ hybridization method
      [Torchia et al., (1994) Am. J. Hum. Genet. 55, 96-104]. We propose that our data
      and those obtained by the in situ method can be accommodated by the existence of
      structural features that differ between the silent and expressed alleles of XIST.
      Similar features may be important determinants of the replication asynchrony
      found by the in situ method for other genes subject to monoallelic expression.

PMID- 7633437
TI  - A human homolog of the S. cerevisiae HIR1 and HIR2 transcriptional repressors
      cloned from the DiGeorge syndrome critical region.
AB  - The DiGeorge syndrome (DGS) is a developmental disorder affecting derivatives of
      the third and fourth pharyngeal pouches. DGS patients present an interstitial
      deletion in one of their two chromosomes 22. Cosmid DAC30 was mapped to the DGS
      smallest critical region. Iterative cDNA library screening initiated with a DAC30
      gene fragment candidate yielded a cDNA contig whose assembled nucleotide sequence
      is consistent with the widely transcribed, 4.2-4.4 kb long, messengers detected
      by northern analysis. The deduced protein sequence, 1017 amino acids in length,
      entirely encompasses the 766 amino acids previously designated as TUPLE1. The
      completed protein has been renamed HIRA because it contains various features
      matching those found in HIR1 and HIR2, two repressors of histone gene
      transcription characterized in the yeast Saccharomyces cerevisiae. Strikingly
      alike in their N-terminal third, HIRA and HIR1 contain seven copies of the WD
      repeat, a motif implicated in protein-protein interactions, suggesting that they
      might define a new subfamily of functionally homologous proteins. The remainder
      of the human polypeptide highly resembles a corresponding fragment in HIR2. We
      propose that HIRA, alone, could have a part in mechanisms of transcriptional
      regulation similar to that played by HIR1 and HIR2 together. The presence of a
      single copy of the HIRA gene in DGS patients possibly accounts for some of the
      abnormalities associated with this syndrome.

PMID- 7633441
TI  - Mutation analysis of the RET receptor tyrosine kinase in Hirschsprung disease.
AB  - Hirschsprung disease (HSCR), or congenital aganglionic megacolon, is the most
      common cause of congenital bowel obstruction with an incidence of 1 in 5000 live
      births. Recently, linkage of an incompletely penetrant, dominant form of HSCR was
      reported, followed by identification of mutations in the RET receptor tyrosine
      kinase. To determine the frequency of RET mutations in HSCR and correlate
      genotype with phenotype, we have screened for mutations among 80 HSCR probands
      representing a wide range of phenotypes and family structures. Polymerase chain
      reaction (PCR) and single-strand conformation polymorphism (SSCP) analysis of
      RET's 20 exons for mutations among probands revealed eight putative mutations
      (10%). Sequence changes, which included missense, frameshift and complex
      mutations, were detected in both familial and isolated cases, among patients with
      both long- and short-segment HSCR and in three kindreds with other phenotypes
      (maternal deafness, talipes and malrotation of the gut, respectively). Two
      mutations (C609Y and C620R) we identified have previously been associated with
      multiple endocrine neoplasia type 2A (MEN2A), medullary thyroid carcinoma (MTC)
      and, on rare occasions, HSCR. Thus, while HSCR family members may be at risk for
      developing neuroendocrine tumors, it follows that identical mutations in RET may
      be able to participate in the pathogenesis of distinct phenotypes. Our data
      suggest that: (i) the overall frequency of RET mutations in HSCR patients is low
      and therefore, other genetic and/or environmental determinants contribute to the
      majority of HSCR susceptibility, and (ii) at present, there is no obvious
      relationship between RET genotype and HSCR phenotype.

PMID- 7633442
TI  - High-resolution DNA Fiber-FISH for genomic DNA mapping and colour bar-coding of
      large genes.
AB  - We have applied two-colour fluorescence in situ hybridization (FISH) to DNA
      fibers and combined it with digital imaging microscopy for the mapping of large
      cosmid contigs. The technique was validated using a set of unique plasmids and a
      cosmid contig both originating from the thyroglobulin (Tg) gene and previously
      mapped by restriction analysis. The resolution proved to be close to the
      theoretical lower limit of approximately 1 kb, ranging > or = 400 kb.
      Subsequently a 400 kb cosmid contig derived from a DMD-YAC was directly mapped by
      Fiber-FISH. The resulting map is in full agreement with the restriction map. Two
      colour Fiber-FISH mapping thus showed to be capable for accurately sizing gaps
      and overlaps, and to identify chimeric or repeat sequence containing cosmids
      across a 400 kb region at once. The generated 400 kb 'colour bar-code' was
      subsequently used to map two DMD deletion breakpoints in patient DNA with an
      accuracy of 1-2 kb. The results underscore the value of this method for the
      delineation of chromosomal rearrangements for positional cloning and single
      patient clinical studies.

PMID- 7633443
TI  - A novel dystrophin isoform is required for normal retinal electrophysiology.
AB  - Dystrophin is present in the outer plexiform layer of the retina and is required
      for normal retinal function as measured by electroretinography. We describe the
      identification of a novel isoform of dystrophin (Dp260) present in the mouse
      retina. The unique 5' terminus of the mRNA originates from a newly identified
      exon and is spliced in frame to exon 30 of the Duchenne muscular dystrophy (DMD)
      gene. The retinal isoform of dystrophin has 13 novel amino acids as its N
      terminus followed by most of the dystrophin rod domain and the cysteine-rich C
      terminal domains. Analysis of mouse tissues indicated this isoform of dystrophin
      is expressed in retina, brain and cardiac tissue. Comparison of retinal
      electrophysiology in mdx and mdxCv3 mouse suggests that Dp260 is required for
      normal retinal function.

PMID- 7633444
TI  - Structural organization and developmental expression pattern of the mouse WD
      repeat gene DMR-N9 immediately upstream of the myotonic dystrophy locus.
AB  - The diverse biological consequences of size-expansion of the unstable (CTG)n
      repeat in the myotonic dystrophy protein kinase (DM-PK) gene at chromosome region
      19q13.3, are still poorly understood. Abnormal (CTG)n length may affect either DM
      PK mRNA fate or function, or alternatively, compromise gene transcription by
      distortion of chromatin configuration. In the latter model involvement of
      neighbouring genes in DM upon extreme expansion of the repeat cannot be discarded
      as a possibility and should be studied further. Here we report on the elucidation
      of the complete genomic structure and expression pattern of the mouse DMR-N9 gene
      (called 59 gene in humans), which is at 1.1 kbp upstream of the DM-PK gene. This
      gene contains five exons spanning 7 kbp and codes for a protein of 650 amino
      acids. Two regions of the predicted protein show significant homology to WD
      repeats, highly conserved amino acid sequences found in a family of proteins
      engaged in signal transduction or cell regulatory functions. The start site of
      transcription has been determined and we have identified putative transcription
      factor binding sequences in a 400 bp putative promoter area immediately upstream
      of the transcribed unit. Northern blotting analysis and RNA in situ hybridization
      revealed ubiquitous low expression in all tissues of the mouse embryo and
      enhanced expression in adult brain and testis. The onset of transcription is
      phased early in mouse embryogenesis, before or at day 9.5 of gestation. From day
      14.5 onwards DMR-N9 mRNAs were detected in all neural tissues, especially in the
      telencephalon and mesencephalon. Later, mRNA presence is evident in distinct
      tubules of the mature testis, restricted to secondary spermatocytes of stages
      VIII to XII of the spermatogenic proliferation cycle. We conclude that the DMR-N9
      gene is a candidate for being involved in the manifestation of mental and
      testicular symptoms in severe cases of DM.

PMID- 7633445
TI  - No evidence that common allelic variation in the Amyloid Precursor Protein (APP)
      gene confers susceptibility to Alzheimer's disease.
AB  - In order to test the hypothesis that allelic variation within the Amyloid
      Precursor Protein (APP) gene influences susceptibility to common forms of
      Alzheimer's disease (AD) we screened the entire coding, promoter and 3'
      untranslated sequences of the APP gene for DNA variations in 30 unrelated
      patients and eight controls with probable AD by a combination of RT-PCR PCR and
      chemical cleavage mismatch analysis. Although we were unable to detect commonly
      occurring allelic variants, we were able to detect a novel mutation within the
      APP gene in one individual with late-onset AD. This mutation resulted in the
      substitution of a tryptophan residue for an arginine residue at codon 328 within
      exon 7 which encodes the so-called protease inhibitor domain of the 751 residue
      APP isoform. However, the pathological significance of this mutation is uncertain
      as neither this, nor any other mutation occurring within exon 7 of the APP gene
      was found in any of a further 102 AD patients and 86 age-matched controls. In
      conclusion, it is unlikely that susceptibility to AD results from commonly
      occurring allelic variants of the APP gene and it is even less probable that
      mutations within exon 7 of the APP gene are important risk factors for late-onset
      AD.

PMID- 7633447
TI  - The human protein kinase gene PKX1 on Xp22.3 displays Xp/Yp homology and is a
      site of chromosomal instability.
AB  - We have isolated a gene, PKX1, by virtue of its position within the candidate
      region for chondrodysplasia punctata in Xp22.3. Although data from one patient
      render it unlikely that PKX1 is the CDPX gene, this gene shows several
      interesting features. First, PKX1 appears to encode a novel type of human protein
      kinase that is related to the catalytic subunit of cAMP-dependent protein kinases
      and has striking homology to the DC2 protein kinase from Drosophila melanogaster.
      Second, PKX1 is part of a family of at least four genes or pseudogenes, of which
      three map to the human sex chromosomes. In contrast to all other genes from the X
      specific region of Xp22.3, PKX1 has a homologue on Yp rather than Yq. This is
      intriguing as it indicates that the single pericentric inversion event
      hypothesized to have occurred during primate evolution is not sufficient to
      explain the present X/Y-homology pattern of Xp22.3. Third, we have characterized
      patients with different chromosomal rearrangements in Xp22.3 or Yp and show that
      a high proportion of these have occurred within the PKX1 locus. This suggests
      that the PKX1 gene, besides harbouring a previously described hot-spot for
      illegitimate Xp/Yp-recombination, contains additional sequences predisposing to
      chromosomal breakage events.

PMID- 7633446
TI  - The human Y chromosome homologue of XG: transcription of a naturally truncated
      gene.
AB  - The XG blood group gene spans PABX1, the pseudoautosomal boundary on the X
      chromosome. The first three exons are pseudoautosomal and the remaining seven are
      X-specific. On the Y chromosome SRY and RPS4Y are located in Y-specific sequences
      within 70 kb of the boundary. Transcription from the XG promoter on the Y
      chromosome has been detected by cDNA cloning and PCR-based methods. Splicing of
      the pseudoautosomal exon 3 of XG occurs to multiple sites in Y-specific
      sequences. Transcripts detected include antisense SRY sequences and XG
      approximately RPS4Y hybrid transcripts. The heterogeneity and low abundance of
      transcripts as well as the lack of maintenance of the XG open reading frame in
      all but one transcript argue against a specific Y-chromosome gene product. An
      expressed pseudogene of XG, XGPY, has been mapped to interval Yq11.21. XGPY is
      transcribed and subject to alternative splicing. Sequence comparison suggests
      that XGPY originated from XG by a gene duplication event in the primate lineage.

PMID- 7633448
TI  - Recombinant mapping of the familial hyperinsulinism gene to an 0.8 cM region on
      chromosome 11p15.1 and demonstration of a founder effect in Ashkenazi Jews.
AB  - A gene for autosomal recessive familial hyperinsulinism (HI) (OMIM: 256450), a
      neonatal metabolic disease characterized by inappropriate insulin secretion in
      the presence of severe hypoglycemia, was recently mapped to a 6.6 cM interval
      between the markers D11S926 and D11S928 on chromosome 11p in 15 families (1). In
      the current study we evaluated six additional families and five new markers, and
      further localized the gene between D11S419 and D11S1310. Using genotype data from
      CEPH Version 7 and data generated from this study, this region was estimated to
      be 0.8 cM in length. Significant linkage disequilibrium between markers and the
      HI gene was observed over a region of 10.3 cM (11 pter-D11S926-D11S1308-11pcen)
      for Ashkenazi Jewish chromosomes. Haplotype analysis showed that 12 of 36 HI
      chromosomes, versus one of 36 non-HI chromosomes, bore a specific haplotype for
      D11S419-D11S902-D11S921 (p < 0.0007), strongly suggesting a founder effect in
      this ethnic group.

PMID- 7633449
TI  - The distribution of linkage disequilibrium over anonymous genome regions.
AB  - Linkage disequilibrium (LD), the association of alleles at different loci, is a
      powerful tool for genetic mapping and for investigating, at the population level,
      processes such as recombination, selection, mutation and admixture. Little is
      known about the distribution of LD across mammalian genomes. Therefore, a survey
      was undertaken, using microsatellite loci, to evaluate the distribution of LD
      over several regions of human chromosome 4. Radiation hybrid (RH) and linkage
      maps provided information on physical and genetic distances between these loci. A
      Finnish population sample was genotyped using 32 microsatellite loci, and partial
      marker haplotypes were determined. Assessment of LD was performed, between all
      pairs of loci, using the Fisher's exact test. LD was detected between several
      loci that were separated by more than 1 Mb or 1 cM. Detection of LD was strongly
      associated with small physical distance; its relation to genetic distance was
      more equivocal. This result may support the hypothesis that linkage maps are
      relatively inaccurate over small distances. Our results suggest that LD is widely
      distributed in anonymous regions of the human genome and its use may allow more
      accurate measurement of small genetic distances than does standard linkage
      analysis. Alternative explanations are considered for comparisons in which LD is
      not detected between tightly linked loci.

PMID- 7633450
TI  - Characterization of FMR1 proteins isolated from different tissues.
AB  - FMR1 protein expression was studied in different tissues. In human, monkey and
      murine tissues, high molecular mass FMR1 proteins (67-80 kDa) are found, as shown
      in lymphoblastoid cells lines. The identity of these proteins was confirmed by
      their absence in tissues from patients with the fragile X syndrome and a FMR1
      knock-out mouse. An Ile367Asn substitution in the FMR1 protein did not alter the
      translation, processing and localization of FMR1 proteins in lymphoblastoid cells
      from a patient carrying this mutation. All the high molecular mass FMR1 proteins
      isolated from normal lymphoblastoid cells and cells from the patient with the
      Ile367Asn substitution were able to bind RNA. However, the FMR1 proteins of the
      patient had reduced affinity for RNA binding at high salt concentrations. In some
      human, monkey and murine tissues low molecular mass FMR1 proteins (39-41 kDa)
      were found, which had the same N terminus as the 67-90 kDa isoforms, but differ
      in their C terminus and are therefore most likely the result of carboxy-terminal
      proteolytic cleavage. These low molecular mass FMR1 proteins did not bind RNA, in
      contrast with the high molecular mass FMR1 proteins. The significance of these
      low molecular mass proteins remains to be studied.

PMID- 7633451
TI  - Human cell mutants with very low mitochondrial DNA copy number (rho d).
AB  - Mutants of human Namalwa cells are described, denoted rho d (mtDNA-depleted),
      which contain a very low mtDNA copy number. Three isolates, denoted FV02, FV03
      and FV05, each selected on the basis of their pyruvate-dependent phenotype, were
      shown to have severely reduced mitochondrial respiratory functions consistent
      with results of histochemical and cytochrome analysis. Analyses of mtDNA by the
      polymerase chain reaction (PCR) and Southern blotting indicated that FV02, FV03
      and FV05 each contained a full complement of mtDNA sequences, 16.6 kb in length,
      in circular form but at a greatly reduced level compared with that of parent rho
      + cells. Quantitative PCR tests showed first, that the parent Namalwa rho + cells
      contain about 1800 molecules of mtDNA and second, that cells of each of FV02,
      FV03 and FV05 contain between 100- and 1000-fold less mtDNA than rho + cells.
      Subclones of each of FV02, FV03 and FV05 all contained detectable mtDNA, thus
      eliminating the possibility that these isolates are mixtures of rho o (devoid of
      mtDNA) and rho + cells. Each of the rho d cell lines FV02, FV03 and FV05 had a
      more rapid growth rate than the corresponding rho o cells but less than that of
      the parent Namalwa rho + cells. The experimentally induced rho d cells described
      here may represent a useful model for human diseases in which severe depletion of
      cellular mtDNA levels in tissues is encountered.

PMID- 7633452
TI  - Neurofibromatosis 1 (NF1) mRNAs expressed in the central nervous system are
      differentially spliced in the 5' part of the gene.
AB  - The neurofibromatosis 1 gene seems to play essential roles at several different
      stages of life. During embryogenesis, it is involved in cardiac development while
      in the adult, neurofibromin (the corresponding protein) is mainly expressed in
      the nervous system, and therein, essentially in neurons, non-myelinating Schwann
      cells and oligodendrocytes. In addition, the NF1 gene is considered a tumor
      suppressor gene, since mutations have been associated with the occurrence of
      benign and malignant tumors in neuralcrest-derived tissues. Using reverse
      transcription-polymerase chain reaction (RT-PCR) analyses with primers located in
      exons 7 and 13, we have identified evidence of alternative splicing in this
      region of the NF1 gene. Cloning and sequencing of cDNA allowed the
      characterization of an isoform bearing an extra 30 bp sequence between exons 9
      and 10a, leading to the insertion of 10 amino acids between residues 420 and 421
      of neurofibromin. The insertion is conserved in the mouse. Examination of the
      pattern of expression of this isoform demonstrated a high level of expression in
      the central nervous system and an absence of expression in all the other normal
      tissues tested including peripheral nervous tissues derived from the neural
      crest. Analysis of brain tumors indicated a reduced expression of the alternative
      exon in medulloblastomas and oligodendrogliomas. The results presented here are
      consistent with tissue-specific expression of this alternative exon which we
      propose to call exon 9br.

PMID- 7633453
TI  - Mitochondrial DNA diversity in the Kuna Amerinds of Panama.
AB  - Mitochondrial DNA (mtDNA) haplotype diversity was determined for 63 Chibcha
      speaking Kuna Amerinds sampled widely across their geographic range in eastern
      Panama. The Kuna data were compared with mtDNA control region I sequences from
      two neighboring Chibchan groups, the Ngobe and the Huetar; two Amerind groups
      located at the northern and southern extremes of Amerind distribution, the Nuu
      Chah-Nulth of the Pacific Northwest and the Chilean Mapuche; and with a single Na
      Dene group, the Haida of the Pacific Northwest. The Kuna exhibited low levels of
      mitochondrial diversity as had been reported for the other two Chibchan groups
      and, furthermore, carried only two of the four Amerind founding lineages first
      reported by Schurr and coworkers (Am. J. Hum. Genet. 1990; 46: 613-623). We posit
      that speakers of modern Chibchan languages (henceforth referred to as the
      Chibcha) passed through a population bottleneck caused either by ethnogenesis
      from a small founding population and/or subsequent European conquest and
      colonization. Using the approach of Harpending et al. (Curr. Anthropol. 1993; 34:
      483-496), we estimated a Chibchan population bottleneck and subsequent expansion
      approximately 10,000 years before present, a date consistent with a bottleneck at
      the time of Chibchan ethnogenesis. The low mtDNA diversity of Kuna Amerinds, as
      opposed to the generally high levels of mtDNA variation detected in other Amerind
      groups, demonstrates the need for adequate sampling of cultural or racial groups
      when attempting to genetically characterize human populations.

PMID- 7633454
TI  - Localization of a novel X-linked congenital stationary night blindness locus:
      close linkage to the RP3 type retinitis pigmentosa gene region.
AB  - X-linked congenital stationary night blindness (CSNBX) is a non-progressive
      retinal disorder characterized by decreased visual acuity and loss of night
      vision. CSNBX is clinically heterogeneous with respect to the involvement of
      retinal rods and/or cones in the disease. In this study, we localize a new locus
      for CSNBX to Xp21.1, thus providing evidence that CSNBX is also genetically
      heterogeneous. A clear correlation between different genotypes and phenotypes
      cannot be found yet. The new CSNBX gene described here is closely linked to the X
      linked retinitis pigmentosa type 3 gene region, which supports the hypothesis
      that there may be a functional relationship between congenital stationary night
      blindness and retinitis pigmentosa.

PMID- 7633455
TI  - Nucleotide sequence analysis of the apolipoprotein B 3' VNTR.
AB  - Variable number of tandem repeat (VNTR) loci typically exhibit high rates of
      germline mutations that alter allele length and thus are ideal models for
      examining processes governing repeat sequence instability. We have characterized
      by nucleotide sequencing the internal structure of the apolipoprotein B (Apo B)
      3' VNTR in a sample of same- and different-sized alleles previously associated
      with flanking marker haplotypes. Significant linkage disequilibrium between
      flanking polymorphisms and minisatellite alleles excludes unequal recombination
      as the predominant mechanism of mutation at the Apo B VNTR and is consistent with
      intra-allelic mutational processes such as replication slippage and/or unequal
      sister chromatid exchange. Diversity among different length alleles was
      distinctly polar and was usually attributable to changes in copy number at one
      particular repeat sequence. Analysis of predicted secondary structures for the
      dimeric repeats demonstrated a relationship between variability and the potential
      to form self-complementary intermediates. Preferential instability of the
      variable repeat: (i) was a function of its location within the tandem array; (ii)
      was not solely dependent on copy number; and (iii) may be related to the base
      composition of the VNTR and the degree of self-complementarity between the
      dimeric repeat sequences. The data suggest that polarized variability may be
      independent of the mutational process(es) generating length variation at
      minisatellite loci and suggest a possible alternative mechanism of mutation that
      involves the formation of secondary structures.

PMID- 7633456
TI  - A third locus for hereditary haemorrhagic telangiectasia maps to chromosome 12q.
AB  - Hereditary haemorrhagic telangiectasia (HHT) or Rendu-Osler-Weber disease is an
      autosomal dominant vascular disorder which associates epistaxis, mucocutaneous
      and visceral telangiectases, and recurrent haemorrhage with chronic anaemia and
      visceral shuntings. Recently, the tumour growth factor (TGF)-beta binding protein
      endoglin localized to 9q33-34 was identified as responsible for HHT in several
      large kindreds with pulmonary arteriovenous malformations (PAVMs). Additional
      linkage studies demonstrated that HHT is a genetically heterogeneous disorder
      with families unlinked to this region of 9q. In the families in which HHT was not
      linked to chromosome 9, less PAVMs were present. Furthermore, in one of these
      families, HHT was found linked to 3p22, where the TGF-beta II receptor is
      located. In this linkage study, we have analysed DNA from two families, in which
      HHT was unlinked to chromosome 9q and 3p, and PAVMs were absent, with a series of
      genetic markers on the centromeric region of chromosome 12. Using two-point
      linkage analysis, a significant lod score of Zmax = 7.86 at theta = 0.05 was
      obtained with the D12S85 microsatellite marker.

PMID- 7633457
TI  - Correlation between fragment size at D4F104S1 and age at onset or at wheelchair
      use, with a possible generational effect, accounts for much phenotypic variation
      in 4q35-facioscapulohumeral muscular dystrophy (FSHD)
AB  - In facioscapulohumeral muscular dystrophy (FSHD), the wide range of clinical
      severity observed both within and between families has obscured past attempts to
      identify any phenotypic differences between families from which phenotype
      genotype correlation could proposed, although it is noted that age at onset is
      youngest and severity greatest in isolated cases. From 14/16 large 4q35-linked
      FSHD families, and 25/34 isolated cases exhibiting a de novo D4F104S1 DNA
      fragment, we find a significant correlation between proband age at onset and FSHD
      associated D4F104S1 fragment size (r = 0.56; p < 0.001), with the smallest
      fragments occurring in isolated cases. A similar correlation (r = 0.70; p < 0.01)
      with fragment size is observed for age to loss of ambulation in 16 subjects using
      a wheelchair. We find also that age at onset appears younger with successive
      generations in the 4q35 families. We propose that fragment size at D4F104S1,
      together with a possible generational effect, accounts for a significant part of
      the wide phenotypic variation in FSHD. Our results predict a more limited range
      for severity within families, and in one family with a 4q35-linked 38kb fragment
      support scapulohumeral presentation without facial involvement as a late onset
      variant of FSHD. We propose that in FSHD, quantitative variation in a uniform
      mutation mechanism influences age at onset, but by deletion rather than expansion
      of DNA.

PMID- 7633458
TI  - A homozygous nonsense mutation in the alpha 3 chain gene of laminin 5 (LAMA3) in
      lethal (Herlitz) junctional epidermolysis bullosa.
AB  - The inherited mechanobullous disorder, junctional epidermolysis bullosa (JEB), is
      characterized by extensive blistering and erosions of the skin and mucous
      membranes. The diagnostic hallmarks of JEB include ultrastructural abnormalities
      in the hemidesmosomes of the cutaneous basement membrane zone, as well as an
      absence of staining with antibodies against the anchoring filament protein,
      laminin 5. Therefore, the three genes encoding alpha 3, beta 3 and gamma 2 chains
      of laminin 5, known as LAMA3, LAMB3 and LAMC2, are candidate genes for JEB. We
      have previously demonstrated mutations in the LAMB3 and LAMC2 genes in several
      families with JEB. We initiated mutation analysis from an affected child by PCR
      amplification of individual LAMA3 exons, followed by heteroduplex analysis.
      Nucleotide sequencing of heteroduplexes identified a homozygous nonsense mutation
      within domain I/II of the alpha 3 chain. These findings provide the first
      evidence that nonsense mutations within the LAMA3 gene are also involved in the
      pathogenesis of JEB, and indicate that mutations of all three genes of laminin 5
      can result in the JEB phenotype.

PMID- 7633459
TI  - Definition of the blepharophimosis, ptosis, epicanthus inversus syndrome critical
      region at chromosome 3q23 based on the analysis of chromosomal anomalies.
AB  - Blepharophimosis syndrome (BPES) is an autosomal dominant disorder of
      craniofacial development, the features of which are small palpebral fissures
      (blepharophimosis), drooping eyelids (ptosis) and a skin fold arising from the
      lower eyelid (epicanthus inversus). The chromosomal localization and identity of
      the BPES locus is not known with certainty. In the current paper, DNA samples
      from three individuals with a clinical history of BPES, two with interstitial
      deletions (cases 1 and 2) and one with a balanced translocation (case 3) all
      involving chromosome 3q23, were analyzed. Allele loss studies using short tandem
      repeat markers in cases 1 and 2 suggested that the region between the markers
      D3S1292 and D3S1306 was deleted in both cases. Subsequently, the derived
      chromosomes resulting from the translocation in case 3 were segregated in
      interspecific somatic cell hybrids. Analysis of the resultant hybrids showed that
      D3S1615 was retained in the derived chromosome 3, whereas D3S1316 was retained in
      the derived chromosome 4. In neither case was the marker present in the
      reciprocal hybrid. These results indicate that the BPES critical region lies in
      the D3S1615-D3S1316 interval.

PMID- 7633460
TI  - Molecular analysis of type II 3 beta-hydroxysteroid dehydrogenase gene in
      Japanese patients with classical 3 beta-hydroxysteroid dehydrogenase deficiency.

PMID- 7633461
TI  - PCR analysis of the Y chromosome long arm in azoospermic patients: evidence for a
      second locus required for spermatogenesis.

PMID- 7633462
TI  - SSC polymorphisms in interleukin genes.

PMID- 7633463
TI  - Isolation and characterization of apolipophorin-III from the giant water bug
      (Lethocerus medius).
AB  - Upon injection of synthetic adipokinetic hormone, lipophorin from Lethocerus
      medius decreased in density and became associated with apolipophorin-III (apoLp
      III). ApoLp-III isolated from hemolymph of Lethocerus medius had a M(r) = 19,000
      and an amino acid composition high in methionine, in comparison with other apoLp
      IIIs. Its circular dichroism spectrum was consistent with a protein with
      secondary structure of predominantly alpha-helix. NH2-terminal sequence alignment
      with apoLp-III sequences from other species showed a conservation of the
      hydrophobic or hydrophilic properties of residues at each position rather than of
      specific amino acids. ApoLp-III from Lethocerus medius has the potential to form
      amphipathic alpha-helices, similar to those found in the three-dimensional
      structure of Locusta migratoria apoLp-III. A portion of the apoLp-III molecules
      that are not associated with lipophorin contained the blue chromophore,
      biliverdin.

PMID- 7633465
TI  - The use of a juvenile hormone binding protein for the quantitative assay of
      juvenile hormone.
AB  - The suitability of the haemolymph juvenile hormone binding protein (JHBP) of
      Locusta migratoria for use in a competition assay for juvenile hormone (JH) III
      has been investigated, and a simple quantitative assay procedure using this
      protein has been developed. JHBP partially purified from haemolymph of precocene
      treated adult locusts gives rapid and stable binding of [3H]10R-JH III, and can
      be separated from the unbound hormone with hydroxylapatite (HAP). The sensitivity
      of the method is such that 0.15 pmol (40 pg) 10R-JH III gives 50% displacement of
      [3H]10R-JH III from the binding protein. Competition by JH II is about 5 times
      less and JH I about 10 times less than that by JH III, JH III diol and acid
      compete at least 1000 times less strongly. A procedure for extraction and assay
      of JH from 50 microliters haemolymph samples is described, the interference by
      non-specific haemolymph components is shown to be relatively small, and some data
      on JH III titres in maturing adult locusts are presented.

PMID- 7633464
TI  - Purification, characterization and cDNA sequence of an alkaline chymotrypsin from
      the midgut of Manduca sexta.
AB  - The chymotrypsin in the midgut of Manduca sexta has been purified, characterized
      and the cDNA encoding the protein has been cloned. The enzyme exists as a monomer
      of approx. 24 kDa and shows maximal activity between pH 10.5 and 11.0. Kinetic
      studies reveal that the Michaelis constant (Km) for the synthetic substrate N
      succinyl-Ala-Ala-Pro-Phe p-nitroanilide varies only slightly between pH 7.5 and
      11.5 and the Dixon plot shows a kinetically significant pKa at 9.2. The
      specificity of the purified enzyme was determined to be the peptide bond on the
      carboxyl side of tyrosine, phenylalanine, tryptophan, histidine, leucine,
      threonine and glycine. The protease is inhibited by TPCK, PMSF, chymostatin and
      DFP. A 1 kilobase chymotrypsin cDNA clone was isolated and sequenced. The cDNA
      sequence encodes a preproenzyme with a putative 17 amino acid signal sequence, a
      41 amino acid activation peptide and a mature enzyme of 235 amino acids. The
      isolated clone encodes the highly conserved active site residues (His, Asp, Ser)
      and specificity pocket residues present in bovine chymotrypsinogen B. Northern
      analysis localizes the mRNA for the chymotrypsin to the anterior and middle third
      of the midgut.

PMID- 7633466
TI  - The separation and identification of glutathione S-transferase subunits from
      Orthosia gothica.
AB  - Four subunits of the cytosolic glutathione S-transferase (GST) in Orthosia
      gothica fed on willow leaves and a semisynthetic bean diet were purified as
      separate peaks (subunits 1-4) by a two-step gradient elution from a reverse-phase
      HPLC column after an initial purification by glutathione-Sepharose 1-chloro-2,4
      dinitro-benzene (CDNB). Subunit 1 with a molecular weight of 26.0 kDa
      reconstituted into a GST homodimer with an isoelectric point of 4.8 and the N
      terminal amino acid sequence (27 steps) indicated a relationship to the class
      theta GST of Musca domestica in the first 10 steps (50% homology), but also to
      the GST class pi of Caenohrabditis elegans (50% between steps 10 and 20). The
      three subunits 2-4 all had a molecular weight of 23.5 kDa and the isoelectric
      points of the reconstituted homodimers were > 9.0. The N-terminal amino acid
      sequence was determined (24 steps) and was identical for the three subunits. A
      high identity of sequence to the GST in C. elegans (70% between steps 1 and 17),
      and a low homology (25%) to the O. gothica subunit 1 was observed. Thus, we
      suggest the O. gothica subunit 1 belong to a different class (O. gothica GST
      class 1) of GST than subunits 2-4 (O. gothica GST class 2). When the larvae
      hatched and fed on a semisynthetic bean diet, subunits 3 and 4 were not present
      in the HPLC eluate, and the subunit 2/subunit 1 ratio increased compared to the
      corresponding ratio in the larvae which hatched and fed on willow leaves until
      the third instar.

PMID- 7633468
TI  - Mosquito vitellogenin receptor: purification, developmental and biochemical
      characterization.
AB  - Vitellogenin receptors (VgRs) play a critical role in egg development of
      oviparous animals by mediating endocytosis of the major yolk protein precursor,
      vitellogenin. A modification of the method for extracting the mosquito (Aedes
      aegypti) VgR from ovary membranes resulted in an 11-fold higher yield and 56-fold
      increase in relative purity of the VgR, in turn permitting purification, antibody
      production, and microsequencing. A Kd of 15 nM was estimated from binding assays
      for the enriched VgR, indicating a very high affinity for its ligand.
      Immunoprecipitation of [14C]VgR using anti-VgR polyclonal antibodies followed by
      SDS-PAGE under reducing conditions and fluorography demonstrated that the 205 kDa
      VgR does not consist of subunits held together with disulfide bonds. However, an
      immunoblot of the native VgR suggests that it exists as an approximately 390 kDa
      noncovalent homodimer in its native state. Immunoblot assays confirmed that the
      VgR is present only in ovarian tissue. A quantitative immunoassay of VgR extracts
      showed that VgR was present in previtellogenic ovaries on the day of emergence,
      increasing from 2 ng to more than 10 ng per ovary by day 5. After initiation of
      vitellogenesis and onset of Vg uptake, VgR quantity increased rapidly between 8
      and 24 h after a blood meal, then began to decline between 24 and 36 h.
      Immunocytochemistry confirmed the presence of substantial amounts of the VgR in 4
      day-old previtellogenic oocytes. In both previtellogenic and vitellogenic
      ovaries, the VgR was present only in the oocyte, primarily in the cortex.

PMID- 7633467
TI  - Molecular analysis of a Drosophila melanogaster sn-glycerol-3-phosphate
      dehydrogenase allozyme variant that has cold labile activity.
AB  - A rare naturally occurring allele, GpdhACb62, at the sn-glycerol-3-phosphate
      dehydrogenase locus in Drosophila melanogaster, encodes an enzyme with an
      electrophoretic mobility that is more cathodal than that produced by the common
      slow electrophoretic allele. After electrophoresis and staining of extracts of
      single adult flies there is a single band of activity corresponding in position
      to GPDH-1, but, using highly concentrated extracts, a faint band corresponding to
      GPDH-3 is observed. In GpdhACb62 homozygotes there is about 26% of the normal
      level of activity in adults, and less than 6% in third instar larvae. The
      reduction in activity is significantly greater than the decrease in GPDH
      immunologically cross-reacting material (CRM). Northern analyses, and rapid
      amplification of the cDNA ends (RACE) of the 3' regions of the transcripts, show
      that the levels and structures of the poly(A)+RNAs are similar in homozygotes for
      GpdhACb62 and for a normal activity allele GpdhAC8. Hybridization to
      oligonucleotide probes specific for the GPDH-1 and GPDH-3 transcripts was of a
      similar intensity in GpdhACb62 and GpdhAC8 adult flies. In third instar larvae
      the main transcript is for GPDH-3 and again the hybridization signals were
      similar in each line. The activity of the enzyme produced by GpdhACb62 was
      unstable both at 50 degrees C and at 0 degrees C. The activity lost at 0 degrees
      C was recovered by incubation at 20 degrees C. The complete GpdhACb62 gene, and
      the partial Gpdh tandem duplication 3' to this gene, were cloned and sequenced.
      Comparisons with two normal activity GpdhF genes revealed 31 unique changes in
      the first copy of GpdhACb62. In exon 4, a T to G substitution changes cysteine to
      glycine and may disrupt a disulphide bond and be responsible for the distinctive
      properties of GPDH-ACb62.

PMID- 7633469
TI  - Cloning of an ecdysone receptor homolog from Manduca sexta and the developmental
      profile of its mRNA in wings.
AB  - Using the Drosophila melanogaster ecdysone receptor (DmEcR) B1 cDNA clone, we
      isolated three genomic clones for EcR from the tobacco hornworm, Manduca sexta.
      Subsequent isolation and sequencing of several cDNAs yielded a homolog of the B1
      isoform with 50, 95 and 70% amino acid identities with DmEcR in the N-terminal
      A/B, the DNA binding and the ligand binding domains respectively. Unlike
      Drosophila, an intron occurs between the exons encoding the two zinc fingers of
      Manduca EcR (MsEcR). A 6.0 kb mRNA encoding MsEcR was found in both larval wing
      discs and prothoracic glands and in pupal wings. During the final larval instar,
      the mRNA was maximal in the wing discs at one day after wandering (W1), whereas
      in the prothoracic gland EcR mRNA increased rapidly to high levels on day 2 and
      remained high thereafter. During the onset of adult development, two peaks of EcR
      mRNA were observed in wings from day 3 to 5 and on day 8 after pupal ecdysis.
      These two peaks correlated with the time of increasing titers of ecdysone (E) and
      20-hydroxyecdysone (20E), respectively. The EcR mRNA peaks always preceded the
      large ecdysteroid peak, suggesting that the transcription of the EcR gene is
      induced by a low concentration of ecdysteroid in vivo.

PMID- 7633472
TI  - Endoscope modifications for laser prostatectomy.
AB  - Prior to the development of the technique of laser prostatectomy, contemporary
      modifications to resectoscope design for transurethral prostatectomy had been
      scant. With the introduction of laser prostatectomy and the characterization of
      the "mini-TURP" technique, a new demand for improved continuous-flow cystoscopes
      and resectoscopes has developed. The ideal cystoscope design for laser
      prostatectomy would require the following: (1) continuous irrigant flow for
      optimum cooling of the laser element; (2) a large inflow port so that flow is not
      impaired by the presence of the fiber in the working channel; (3) a large outflow
      port to maximize irrigant flow; and (4) a fiber stabilizer to enable easy
      manipulation of the fiber in the center of the viewing field. The ideal
      resectoscope design for laser prostatectomy would require the following: (1)
      continuous flow of irrigant for cooling of the laser fiber; (2) stabilization of
      the laser fiber in the center of the field of view; (3) the ability to
      interchange electrocautery loops with laser fibers without changing the sheath;
      and (4) the ability to apply laser energy to tissue with the same Iglesias action
      used in transurethral resection of the prostate (TURP). This review analyzes the
      features of the new continuous-flow cystoscopes and resectoscopes manufactured
      specifically for use in laser prostatectomy. All manufacturers were requested to
      submit their most up-to-date literature and photographs of the specific
      instruments they manufacture. The technical specifications, advantages, and
      disadvantages of each instrument are discussed.

PMID- 7633470
TI  - The silkmoth homolog of the Drosophila ecdysone receptor (B1 isoform): cloning
      and analysis of expression during follicular cell differentiation.
AB  - To understand the role that 20-hydroxy-ecdysone (20E) plays during ovarian
      development in Bombyx mori, we have undertaken the cloning of the silkworm
      ecdysone receptor (EcR) and a study of its expression during follicular cell
      differentiation. We have cloned a cDNA that contains a complete open reading
      frame for a 68.1 kDa polypeptide that shares extensive similarities with the B1
      isoform of the Drosophila EcR. The presumed silkmoth EcR (BmEcR) is encoded by a
      single copy gene whose length is in excess of 23 kb. A portion of this gene
      encompassing seven exons that constitute the cloned BmEcR cDNA was also
      characterized. Employment of monoclonal antibodies, directed against the DNA
      binding domain of the Drosophila EcR, in Western blot analyses revealed the
      presence of a major 70 kDa polypeptide in extracts of follicular cells and other
      silkmoth tissues. The mRNA and protein encoded by BmEcR are present in constant
      amounts in follicular cells throughout vitellogenesis but disappear transiently
      at the onset of choriogenesis and reappear during the later stages of
      choriogenesis. The down-regulation of BmEcR in follicular cells during oogenesis
      suggest a complex relationship between 20E, the induction of the program of
      chorion gene expression in follicular cells during mid-vitellogenesis and the
      execution of this program at the end of vitellogenesis.

PMID- 7633471
TI  - Insect immunity: isolation of three novel inducible antibacterial defensins from
      the vector mosquito, Aedes aegypti.
AB  - The injection of Escherichia coli and Micrococcus luteus into the hemocoel of
      Aedes aegypti induces a potent antibacterial activity in the hemolymph. We have
      purified and fully characterized three 40-residue antibacterial peptides from the
      hemolymph of bacteria-challenged mosquitoes that are absent in naive mosquitoes.
      The peptides are potently active against Gram-positive bacteria and against one
      of the Gram-negative bacteria that were tested. The amino acid sequences clearly
      show that the three peptides are novel isoforms of the insect defensin family of
      antibacterial peptides. They differ from each other by one or two amino acid
      residues. We present here the complete amino acid sequences of the three isoforms
      and the activity spectrum of the predominant Aedes defensin.

PMID- 7633473
TI  - Noncontact sidefire laser ablation of the prostate.
AB  - Continuing experience with Nd:YAG noncontact sidefiring laser fibers over the
      past 4 years has shown encouraging results. Thus far, of the 198 patients treated
      with the 60 W/60 seconds technique since October 1990, a total of 74 were
      available for long-term evaluation (69 at 12 months and 29 at 24 months). The AUA
      Symptom Scores, Qmax (peak uroflow rates), and postvoiding residual urine volumes
      demonstrated marked improvement. The complications included 16 instances of
      recurrent obstructive symptoms necessitating revision. Three patients suffered
      urinary tract infections, two patients developed bladder neck stenosis, four
      anticoagulated patients with clot retention required blood transfusions, and
      three patients had epididymoorchitis. Follow-up at 12 and 24 months showed
      sustained reduction in AUA Symptom Scores and maintained improvement of the peak
      flow rates and residual volumes. These results demonstrate the safety and
      clinical applicability of laser ablation of the prostate and its potential
      usefulness as a less invasive therapy for benign hyperplasia.

PMID- 7633474
TI  - Contact laser vaporization of the prostate: sidefire technique.
AB  - With the development of contact sidefiring fibers, urologists have gained a
      valuable tool to deliver laser energy more precisely into prostatic tissue.
      Contact laser prostatectomy can now be viewed as a well-established procedure
      that offers several distinct advantages over conventional methods such as
      transurethral resection of the prostate. The results of experimental and clinical
      studies are presented, supporting the value of this new modality.

PMID- 7633475
TI  - Gold-tip laser sleeve for a bare fiber.
AB  - A gold-tip laser sleeve for a bare laser fiber has been used for Nd:YAG laser
      irradiation of the prostate in both the canine model and a pilot clinical series.
      In the animal model, irradiation was undertaken using the Ablaser catheter
      through an open suprapubic cystotomy, and the procedure was monitored by video
      endoscopy via a perineal urethrostomy. Intraprostatic heating profiles were
      determined using real-time interstitial thermometry. As long as no carbonization
      occurred, irradiation with higher wattage resulted in higher intraprostatic
      temperatures. The "popcorn effect" caused a superficial temperature reduction but
      did not alter the ability of thermal conduction to heat deeper in the prostate. A
      small series of patients has been treated, with good results.

PMID- 7633477
TI  - Effect of temperature and flow rate of irrigant on coagulation necrosis in canine
      prostate treated with neodymium:YAG laser.
AB  - We studied the effect of the irrigant temperature (5 degrees-38 degrees C) and
      flow rate (100-500 mL/min) on the extent of coagulation necrosis induced during
      Nd:YAG laser irradiation in the canine prostate model. The tissue response was
      quantified based on histopathologic evaluation of the lesions. Changing the
      irrigant temperature or the flow rate within the ranges studied did not
      significantly affect the size of the thermal lesions. The intraprostatic
      temperature distribution during laser irradiation is mainly governed by blood
      perfusion rather than by irrigant variables.

PMID- 7633476
TI  - Combination holmium and Nd:YAG laser ablation of the prostate: initial clinical
      experience.
AB  - The holmium laser is a recent addition to the urologist's armamentarium, being
      used primarily for the destruction of urinary calculi. Its use as a tool for
      ablation of the prostate has not been previously described. Our initial
      experience with 110 patients who have undergone a combination procedure using the
      Nd:YAG laser for standard circumferential coagulation followed by holmium laser
      ablation is reported. A further 32 patients who have had a holmium-only technique
      are described. In the patients who had the combination technique, the AUA Symptom
      Score improved from a mean value of 19.8 preoperatively to 7.8 at 3 months. The
      peak urine flow rate likewise improved, from a mean of 8.9 mL/sec preoperatively
      to 15.1 mL/sec at 3 months. Only one patient who had the holmium-only technique
      required recatheterization, compared with nine patients who had the combination
      procedure. The combination Ho/Nd:YAG laser ablation technique is evolving. The
      early results of the holmium-only technique suggest an advantage over the
      combination with regard to catheterization time and degree of irritative
      symptoms. The longer-term results must be assessed to confirm this impression.

PMID- 7633478
TI  - Nursing management of the laser prostatectomy patient.
AB  - The focus of nursing management for the patient having a laser prostatectomy is
      preoperative preparation and education. Patients often equate an ambulatory
      procedure with rapid symptom relief and may be discouraged and distressed
      postoperatively if they have unrealistic expectations. Training in clean
      intermittent self-catheterization will enable the patient to be catheter free
      while minimizing postvoiding residual volumes.

PMID- 7633479
TI  - Laser prostatectomy: where are we now, and where should we be going?
AB  - Sidefire coagulation of the prostate has been a very successful introduction of
      laser technology to the treatment of prostate disease. Although bleeding has been
      reduced, the delayed relief of urinary obstruction and the postoperative dysuria
      are of concern. Laser vaporization, on the other hand, is probably as good as
      electrical incision of the bladder neck and is less likely to produce bleeding.
      The hybrid technique, a combination of vaporization of the gland substance with
      laser prostatotomies and coagulation, provides early disobstruction with later
      bulk removal of prostatic tissue. Interstitial coagulation seems to be effective
      in treating a greater bulk of gland tissue. Urologists need to subdivide
      prostates according to their size and configuration for a series of clinical
      trials of various types of laser prostatectomy and comparison with established
      treatments.

PMID- 7633480
TI  - Laser prostatectomy devices and their tissue effects.
AB  - Laser systems used for prostatectomy may be right-angle (sidefiring) devices,
      which are either refractive or reflective, or contact devices. The tissue physics
      of these systems differ, and as a result, there are very real differences in the
      optimal exposure techniques. An understanding of the device being used is
      essential for producing a satisfactory result.

PMID- 7633481
TI  - Laser effects on prostatic tissue: review of experimental data.
AB  - Laser-tissue interaction is a highly dynamic event affected by many features of
      the laser, the tissue, and the operative procedure. The continuous-wave lasers
      used in urology produce lesions in three basic phases: initial heating, protein
      denaturation, and evaporation with charring. There are three components of these
      lesions: a central cavity, a zone of char, and a coagulation zone. The
      configuration of the lesion differs depending on the method of laser ablation
      (noncontact coagulation, contact tip incision, contact free-beam evaporation).
      Understanding of these differences will enable the endourologist to choose
      rationally among the various techniques of laser prostate ablation.

PMID- 7633482
TI  - Monitoring program of biological status of human populations related to
      environmental changes.
AB  - The paper aims at a synthesis of research carried out hitherto which might serve
      to evaluate the diagnostic value of human biological traits related to natural,
      economic and socio-cultural properties of the environment. The development of a
      monitoring program is the object of research of the Department of Human Ecology,
      the Polish Academy of Sciences, in the years 1986-1990 in Poland, and also of
      recommendations of the IUAES Human Ecology Commission for the last decade of the
      20th century in various countries over the world. Generally, the stages of
      ontogenesis that are appropriate for monitoring are those which involve an
      intense proliferation of cells and a rapid growth. The appropriate subjects are
      the more ecosensitive individuals, that is the heterozygous ones as well as men.
      The more ecosensitive traits are those developed after birth in over 50 per cent
      of their adult value. Traits of the highest diagnostic (discriminant) value with
      respect to environmental conditions were selected. The results are based on the
      analysis of: 35 somatic traits in 1034 newborns from Bialystok and Zambrow in
      relation to the traits of their families and parents; 21 somatic traits in 2461
      of 11 year-old children from Lublin; 40 somatic, physiological and psychomotor
      traits in 1186 children, 6-19 years old from Poland; 26 morphological and
      physiological traits in 4771 subjects of 5-90 years of age in Poland; 9 somatic
      and 17 motor traits in 127,489 children, 7-19 years old, in relation to economic
      and demographic conditions in 98 regions of Poland; and 27 somatic, physiological
      and psychomotor traits in children and their parents from the ages of 3-80 years,
      from 3995 families from Poland. The age particularly important to the study
      includes: foetal growth effects recorded as newborn status, child development
      from about half a year (since weaning) to about 3 years of age, development at
      the early period of puberty, the period at adolescence, age at the peak value
      (maximal size, best results) of the main morphological and functional traits
      (usually between the age of 12 and 30), and finally, the rate of involution of
      these main traits in older age. For the "minimum program" (for public health and
      environmental conservation services) among somatic traits, 3 were selected for a
      minimum program: stature, Kaup index, and cephalic index. Among physiological
      traits, 2 were selected: forced respiratory volume per second and hemoglobin
      concentration. Among motor traits, 3 were selected for the minimum program:
      distant movement accuracy, grip strength, and standing long jump.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7633484
TI  - The concept of hierarchy in general systems theory.
AB  - The paper reviews main ideas related to the concept of hierarchy as they are
      discussed in contemporary general systems theory. After presenting a dictionary
      definition of the concept, the author examines the intuitive idea of hierarchy
      quoting Mario Bunge's notion of level structure. Then relationship between two
      other concepts: a system and a hierarchy is characterised on the bases of
      Bowler's, Bunge's again, Klir's, and the author's studies. Finally, the paper is
      concluded that hierarchy is not an otological concept but epistemological one.

PMID- 7633483
TI  - Family characteristics and offspring growth in various countries. II. Stature of
      offsprings in various families in Japan and Korea.
AB  - The stature of 1219 offspring was examined in 578 families in Japan, and of 672
      offspring in 265 families in Republic of Korea. Several traits of parents were
      investigated, on which using factor analysis four latent factors were extracted.
      In Japan they consisted of parent's age at child birth (F1), culture level and
      income (F2), family and apartment size (F3), and genetic factor (F4). The same
      factors were identified in Korea, but the first two in reverse order. The value
      of each factor was coded as one when below the median and as 2 when above the
      median. Using this code, 16 family types were distinguished ranging from 1111 to
      2222. The stature of offspring was recalculated in age-independent T-scores. In
      Japan, family types "maximizing" the stature of offspring were 1122 for boys and
      1222 for girls, whereas in Korea 1222 for both sexes, opposite were "minimizing".
      In the rich populations representing the civilization of the Far East, the
      factors promoting tall stature of offspring included the low culture-income
      factor and large family, thus the factors promoting short stature in poor Polish
      populations belonging to the Western civilization. It is not clear whether this
      could have been related to the economic status or to different civilization
      systems.

PMID- 7633486
TI  - Remarks on the mechanism of demographic behaviour.
AB  - The main idea, on which discussion presented in this work is concentred cosists
      in the conviction, that the observed demographic regularities are the result of
      individual struggle with the daily difficulties of the units constituting
      populations, and the belief, that the essence of human existence is rooted in the
      permanent process of adaptations. On the base of above, it has been assumed that
      demographic transformations are result of two forces. First of them is formed by
      biological determinants, forcing human sociates to function in the environment in
      a way which would maximize both--ability to survive and multioly, and the result
      of these strifes in expressed by the guarantees of population existence.
      Resistance of environment is another force influencing demographic
      transformations.

PMID- 7633488
TI  - Territorial evolution in an Italian rural village through historical
      documentation.

PMID- 7633485
TI  - Computer modelling of processes in ecosystems--general principles.
AB  - Concept of the mathematical modelling of ecosystems is presented, starting with a
      set of variables and a set of relations. Examples are given for the models of
      plant populations in terrestrial ecosystems. The differences between well
      structured and ill-structured problems are shown with some methodological
      consequences for strategy of applications of computer models.

PMID- 7633487
TI  - Seasonal rhythm of menarche as a sensitive index of living conditions.
AB  - The paper is focused on the seasonal pattern of birth and occurrence of menarche
      in different populations. The material collected in 1988/89 consists of 522 girls
      and their 249 mothers from schools of Merida, and of 135 girls and their 66
      mothers from Progreso (Yucatan, Mexico). Occurrence of a biorhythm due to which
      girls matured in the month of their birth more frequently than by chance, was
      found. A shift of the maturation to an earlier or later month is caused by stress
      acceleration up or delaying maturation. Seasonal differences in menarche occur in
      different climates, but they depend on seasonal differences in the life style,
      occupation, and the like, rather than on climate itself. Typically menarche
      occurs in the extreme periods in terms of climate, diet, hard work, stress, etc.,
      that is, in summer and/or in winter. The age of mother's maturation is correlated
      with that of daughter's. Month of daughter's maturation is correlated with that
      of mother's. Correlation exists between the month of woman's birth and the month
      of her maturation. No correlation exists between the month of daughter's birth
      and that of mother's, and between the month of daughter's maturation and the
      month of mother's birth.

PMID- 7633489
TI  - Family characteristics and offspring growth in various countries. III. Regression
      of offspring's stature in relation to parent's and family's factors in Japan and
      Korea.
AB  - 1219 offspring 2-48 years old were examined in 578 Japanese and in 672 Korean
      families. To obtain age-independent values, we used 100-point T-scores. A
      multiple regression analysis, shows that the (tall) stature of Japanese offspring
      dependent on the genetic factor (tall stature of parents) in about 13%, on
      (large) family and apartment size in 0.4-1.5%, for sons also on (good) education
      and income of parents in 0.72%, and for daughters on (young) age of parents at
      child birth. In Korea, the (tall) stature of offspring was significantly related
      to the genetic factor (tall parents), which explained 1.8% of the variance for
      sons and 13% for daughters, and also to the (large) family apartment size, which
      explained 2.6% of the variance for sons and 0.84% for daughters. These results
      show in a different light the results obtained from the analysis of family types,
      and they provide evidence for the importance of the analysis of sets of traits in
      the form of family types, going beyond the importance of other multivariate
      techniques.

PMID- 7633490
TI  - Potential independent factors of variability of biological status and
      reproductive history of Yucatecan women.
AB  - In this paper, we report the results of the application of principal component
      analysis (PCA) in a study of the human ecology of rural-to-urban migrantion in
      Yucatan, Mexico. Socioeconomic, reproductive and anthropometric data from 216
      women 32 years of age or older, were obtained in 1989-1990. Seventeen
      socioeconomic, demographic and environmental properties of the families of such
      women, plus migrant status, were employed in a PCA, which yielded five
      independent factors, explaining 57.1% of the total variance of such properties.
      These factors were employed to made a multiple regression analysis on 19
      anthropometric and 21 reproductive traits, age adjusted. According to the
      multiple regression of women's biological status to independent factors, we found
      that in better living conditions (Factor 3), women are heavier, taller, with more
      body surface and subcutaneous fat in the trunk and in the upper extremity, than
      in worse living conditions. Better educational level of wife and husband (Factor
      2) is associated with lower number of pregnancies and alive born children, as
      well as less reproductive losses. Women living in families with higher income
      (Factor 4), have a younger age at the first pregnancy, older age at the last
      pregnancy, greater number of pregnancies, alive born children and alive offspring
      at the interview, and they experience less reproductive losses in relation to the
      number of pregnancies. This fact suggests that for the families in this sample,
      big families are a strategy to cope with poverty and uncertainty in employment
      and income. Our results are discussed against the reports in the literature.

PMID- 7633491
TI  - Family characteristics and offspring growth in various countries. I. Frequency of
      various family types in Bulgaria, Japan, Korea, Mexico and Poland.
AB  - 9936 families were analyzed from Bulgaria, Japan, Korea, Mexico, and Poland. A
      factor analysis revealed four factors: culture (F1), income (F2), genetics (F3),
      and family and apartment size (F4). Family types we coded as 1 if below the
      median and 2 if above the median. The most frequent types were represented by
      1122, 2221, and 2211 (frequency 8.7-8.0%), and the least frequent by 1221 and
      2111 (frequency 4.2-4.3%). Some similarity with respect to family types were
      found between populations: from Polish regions with heavy industry and seaside
      regions; from Polish towns under industrialization and from Mexico; from the
      Polish medium-size town of Lublin and Bulgarian towns; from Polish villages; from
      Polish mountain areas and north-eastern towns; from Korea; from Japan; from
      Polish cities.

PMID- 7633493
TI  - Assortative mating in somatic traits and its consequences.
AB  - The problem of assortative mating embraces non-random mating of spouses. However,
      it is often discussed together with its consequences, which results from the fact
      that when we study similarities between spouses at various stages of their
      acquaintance and/or living together we must take into consideration not only the
      criteria of mating but also the consequences like, for instance, "resembling"
      (synchronous changes in husband and wife) and perhaps compensation of one's
      traits. This problem has not been sufficiently examined so far and further
      studies are necessary (Wolaanski 1970c, Nikityuk and Filipov 1975, Kasprzak and
      Wolanski 1977, Thiessen and Gregg 1980, James 1989). The problem of assortative
      mating involves both the reasons principally genetic-evolutionary problems
      (Pearson 1896, Wolanski and Siniarska 1983, 1984)--and the consequences as well,
      like, for instance homosis, that is transmitting to the offspring similar genes
      from defined loci, and heterosis, that is transmitting the different genes. Thus
      problem constitutes genetic foundations of auxology. Also an ecological problem
      is added, namely a synchronous resemble changes of spouses connected with similar
      living conditions and life style. Assortative mating seems to be a simple problem
      but in fact it is a scientific problem in which genetic, ecological and
      auxological approaches are combined. Below we will discuss assortative mating
      from these angles with reference to some anthropological traits. As a matter of
      fact, assortative mating is concerned with such a fundamental problem in the
      biomedical and social sciences as development the traits of the offspring
      (organism level) and of the whole future generations (population level). This is
      a problem of great importance by no means theoretical only. In our studies the
      main emphasis has been on spouses similarities in the morphological,
      physiological and psychomotor traits and also on some changes in the successive
      generations (which was connected with the lasting of marriage before the moment
      of investigations). The variations of traits of the populations were also taken
      into consideration as well as the effects of assortative mating of spouses on the
      development of their children. The above mentioned problems will constitute the
      contents of the present chapter. Studies on assortative mating have had a long
      tradition in Poland and most probably are one of the earliest in the world, apart
      from those conducted by Pearson (1896) in Great Britain and the Anonymous ones
      from 1903. This pertains mostly to B. Rosinski's (1923, 1925, 1926, 1929)
      investigations conducted in Poland in 1918 and on Polish immigrants to Brazil in
      1931 and USA in 1929-30 (Stolyhwo 1931, Rosinski 1934).

PMID- 7633492
TI  - Biodemographic and sociocultural factors in two generations of families from six
      Polish rural and urban populations.
AB  - There were investigated 6967 families from 6 rural regions, under
      industrialization, and industrialized urban regions. In the grandparents
      generation there were taken into account 10 traits (an education level, a mating
      radius, and a stature) and in parents generation 17 traits (the mentioned-above
      ones and a number of family members, a flat size, incomes, an employees No., a
      life mode, smoking etc. Numerical characteristics of traits have been calculated
      jointly and separately in six populations, matrices of correlation have been
      constructed and moreover factorial analysis have been carried out, as a result of
      which 8 rotated factors have been obtained. The highest cultural mobility
      (increase in the level of education) from generation to generation occurs in the
      population of textile industry town Lodz. The highest improvement of biological
      status, the increase in mating radius and high incomes are characteristic for
      this regions, too. On the other side are villages with low culture mobility (not
      large increase in education level), slight improvement of biological status,
      almost no migrations, overcrowded flats and low income per family member. The
      relations between pairs of traits appear to vary largely in several populations.
      Generally is a high correlation between the education level of the same family
      members in both generations. The has been stated negative correlation between
      grandfather stature both of the mother and the father lines, with occurring of
      positive assortative mating in the couples of two generations. In both
      investigated generations there is the positive assortative mating, but the
      negative correlation in the stature between grandfathers of the mother and the
      father lines. The grandparents education level is correlated with their and their
      offsprings stature. The duration of holidays is one of the best (closely
      correlated with others) indicators of life mode, and partially of a given family
      living conditions, too. 8 hidden factors have been separated: a consciousness,
      mode of life, a number of family members, a genetic factor (stature), migrations,
      living conditions, incomes. This 8 factors have different ranks (evaluated as a
      position in sequence expressing in % the share in being explained variance) in
      six investigated rural and urban populations, explaining together 54-55% of the
      total variance of analyzed family traits. The consciousness occurs generally as a
      first factor. As far, as the mode of life is concerned, the rank of its factor is
      less in villages than in towns, and reciprocally the ranks of such factors as a
      number of family members, migrations and living conditions, are greater in
      villages than in towns.

PMID- 7633495
TI  - [Video assisted thoracic surgery: reflexions].

PMID- 7633494
TI  - [How far should AIDS treatment go].

PMID- 7633496
TI  - [The curriculum of the clinician].

PMID- 7633497
TI  - [Usefulness of paraffin embedding as complementary technic in the diagnosis of
      thyroid aspirates].
AB  - PURPOSE: To compare the diagnostic value of conventional direct cytologic smears
      and paraffin embedding in the preparation of samples obtained by fine needle
      aspiration (FNA) biopsy. METHODS: Direct smears and paraffin embedding
      preparations were examined from 100 thyroid lesions. In 9 cases, the FNA smears
      and paraffin embedding blocks were, in addition, compared with surgical thyroid
      specimens. RESULTS: The FNA samples were adequate for diagnosis in the great
      majority of cases (93/100). In 72 aspirates, both smears and paraffin embedding
      preparations were adequate. In 17 cases only he latter preparations and in 4
      specimens only the smears were considered adequate. When both smears and paraffin
      blocks were available (72 aspirates), there was diagnostic agreement in 63 cases.
      Overall the diagnostic percentage of FNA/paraffin-block preparations was 95.7%
      and of FNA/conventional smears was 81.7%. Statistical analysis demonstrated that
      paraffin blocks increased the diagnostic accuracy of thyroid FNA (p < 0.01).
      CONCLUSION: Our data point out to the value of complementing conventional FNA
      smears with paraffin embedding preparations for the diagnosis of thyroid lesions.

PMID- 7633499
TI  - [Second Brazilian consensus on the treatment of arterial hypertension].

PMID- 7633500
TI  - [Benzodiazepines: prescription study in a primary health care unit].
AB  - PURPOSE: The objective of this survey was to study the prescription rate of
      benzodiazepinics in a Primary Health Care Unit, in the city of Pelotas, RS,
      Brazil. METHOD: Every consultation during a 12 month period was recorded,
      including the prescription of drugs. In order to analyze the prescription of
      benzodiazepinics we considered only the 3,368 consultations of patients above 25
      years. RESULTS: Patients whose age ranged from 45-64 years experienced the
      highest prescription rates, benzodiazepinics being the third most prescribed drug
      for males and the fourth for females. CONCLUSION: The results show that
      benzodiazepinics are among the most prescribed drugs.

PMID- 7633501
TI  - [Benzodiazepine consumption in Porto Alegre].
AB  - Benzodiazepines has been largely used to control anxiety and other clinical
      pictures since it began to be traded in the 60's. In recent years, many studies
      have shown that they are used indiscriminately, contributing to increase
      associated morbidity, and to search for other more accessible tranquilizers.
      PURPOSE--To estimate the prevalence of benzoadiazepine and over-the-counter
      tranquilizers use in adults living in Porto Alergre-RS, Brazil. METHODS--480
      inhabitants of Porto Alegre, aged 18 or older, selected through a random cluster
      sampling procedure (sectors of the Brazilian Census), were interviewed in their
      homes during June, 1991. RESULTS--The prevalence for BDZ use during life, in the
      past year and in the past month was, respectively, 46.7%, 21.3% and 13.11%.
      Prevalence was significantly higher among women and widowers or divorced. The
      majority of those who used BDZ during the past month did so at least 2 or 3 days
      per week. More than 40% reported frequent over-the-counter substances use to
      "tranquilize", with a 28.8% prevalence for past month use. CONCLUSION--Chemical
      substance use to alleviate anxiety and other symptoms is generally spread.
      Legislation, not always respected, has been insufficient to discipline its use.
      Understanding the complexity of reasons for the situation to be unchanged is
      needed. Also necessary is the investment in education on adequate use of BDZ,
      both for physicians and population, and the search for legal measures that should
      be more efficient.

PMID- 7633498
TI  - [Transoperative anatomopathologic examinations: quality control].
AB  - Frozen sections (FS) are usually performed in a General Hospital and are very
      useful for the surgical procedure orientation. PURPOSE--To verify the accuracy of
      the FS performed at the Hospital de Clinicas de Porto Alegre (HCPA), RS, Brazil.
      METHOD--2,152 FS were carried out between March 1986-September 1991, in a
      prospective study. RESULTS--3.7% of the conventional pathologic examinations
      (58,127), performed in the same period, correspond to the FS examined. When the
      FS diagnosis differed from the definitive one (in paraffin) it was classified as
      False Positive (0.4%), False Negative (1.8%) or inconclusive (2.8%). The organs
      more frequently examined were lymph nodes (19.3%), ovary (17.21%), breast (16.6%)
      and thyroid gland (12.4%). We observed accuracy indices in 95% of the FS
      examined, and in 97.8% when excluding the inconclusive ones. CONCLUSION--The
      accuracy indices of FS performed in HCPA were similar to the ones found in the
      literature, which vary from 90.4% to 98.5%.

PMID- 7633502
TI  - [Postgraduate studies in the medical field].
AB  - Considerations on a few aspects of postgraduate education in medicine are made:
      1) Concept of stricto sensu of postgraduate study of the physician (who is an MD
      and seeks a second degree of doctor, that is, the PhD); 2) Importance of
      scientific initiation (to shorten stricto sensu postgraduation); 3) Features of
      the postgraduate program (that, having the objective of preparing a scientific
      investigator, has different characteristics of the graduation courses, of
      specialization or advanced courses, of the advisor (who must have a consistent
      line of research), of the doctor-to-be (who must develop his potential of
      creativity) and of the thesis to be prepared (which should generate a paper
      publishable in an indexed international journal).

PMID- 7633503
TI  - [Pancreatitis].

PMID- 7633504
TI  - [Renal transplantation].

PMID- 7633505
TI  - [Hereditary pancreatitis].
AB  - Hereditary pancreatitis (HP) is a rare cause of chronic pancreatitis. Recurrent
      abdominal pain is the most common clinical manifestation, with onset in childhood
      or adolescence. PURPOSE--Report of a case of HP with atypical presentation and a
      review of the literature. METHODS--A non-alcoholic patient, without history of
      abdominal pain, with steatorrhea and malnutrition was investigated. The
      diagnostic evaluation revealed severe chronic pancreatitis. Two close relatives
      with early onset calcifying pancreatitis were detected. Epidemiologic and
      clinical features of HP were reviewed. CONCLUSION--Although uncommon, HP should
      be regarded in the differential diagnosis of chronic pancreatitis. Familial
      screening of suspected cases should be routinely performed.

PMID- 7633506
TI  - [Hepatocarcinoma: analysis of 14 cases].
AB  - In Brazil, hepatocellular carcinoma (HCC) is not a common tumour. Virus B
      hepatitis and cirrhosis play an important role in the development of HCC. The
      authors described 14 cases of HCC registered in our service during the last 33
      months. PURPOSE--Evaluate clinical and laboratory aspects of the hepatocarcinoma
      treated in our service. MATERIAL--Fourteen patients evaluated between 1990 and
      1993 were described. Ten were men the median age was 53 years. RESULTS--The main
      symptoms were: abdominal pain, weight loss and jaundice. Among the fourteen
      patients, 42% percent were positive for HBsAg, 0.7% for anti HCV and 57% were
      cirrhotic. Eighty percent had an advanced disease and serum alphafeto-protein was
      elevated in 92%. The patients underwent different kinds of treatment. Systemic
      chemotherapy was started in 5 patients, however without any response. Surgery was
      done in three patients, one underwent partial resection of the tumour and in the
      others a total resection was carried out. CONCLUSION--The hepatocarcinoma is rare
      in our service, eighty percent had advanced disease and 42% were positive for
      HBsAg.

PMID- 7633507
TI  - [Etiologic diagnosis in allergic diseases].

PMID- 7633509
TI  - The direct perforant path input to CA1: excitatory or inhibitory?

PMID- 7633510
TI  - Perforant path connections to area CA1 are predominantly inhibitory in the rat
      hippocampal-entorhinal cortex combined slice preparation.

PMID- 7633511
TI  - Monosynaptic excitation of hippocampal CA1 pyramidal cells by afferents from the
      entorhinal cortex.

PMID- 7633512
TI  - Intracellular study of direct entorhinal inputs to field CA1 in the isolated
      guinea pig brain in vitro.

PMID- 7633513
TI  - Brief history of cortico-hippocampal time with a special reference to the direct
      entorhinal input to CA1.

PMID- 7633514
TI  - Frequency-dependent alterations in synaptic transmission in entorhinal
      hippocampal pathways.

PMID- 7633508
TI  - [Vasoplegic syndrome: a new dilemma].

PMID- 7633515
TI  - Simulation of perforant path evoked field and intracellular potentials in
      hippocampal CA1 area.

PMID- 7633516
TI  - Another network model bites the dust: entorhinal inputs are no more than weakly
      excitatory in the hippocampal CA1 region.

PMID- 7633519
TI  - Circular dichroism.

PMID- 7633517
TI  - Possible physiological role of the perforant path-CA1 projection.

PMID- 7633518
TI  - Noncovalent forces important to the conformational stability of protein
      structures.

PMID- 7633520
TI  - Infrared spectroscopy.

PMID- 7633521
TI  - Identifying sites of posttranslational modifications in proteins via HPLC peptide
      mapping.

PMID- 7633522
TI  - Urea and guanidine hydrochloride denaturation curves.

PMID- 7633524
TI  - Disulfide bonds in protein folding and stability.

PMID- 7633523
TI  - Differential scanning calorimetry.

PMID- 7633525
TI  - Solvent stabilization of protein structure.

PMID- 7633526
TI  - Site-directed mutagenesis to study protein folding and stability.

PMID- 7633527
TI  - Hydrogen exchange techniques.

PMID- 7633529
TI  - Molten globules.

PMID- 7633530
TI  - Degradative covalent reactions important to protein stability.

PMID- 7633528
TI  - Protein folding kinetics.

PMID- 7633531
TI  - Chaperonin-assisted protein folding of the enzyme rhodanese by GroEL/GroES.

PMID- 7633532
TI  - Fluorescence spectroscopy.
AB  - Although providing extensive detail, the time-resolved experiments described here
      can be quite complex and the instrumentation is not always readily available.
      However, a number of national fluorescence user facilities funded by the National
      Institutes of Health or the National Science Foundation are currently in
      operation and are dedicated to the use of fluorescence spectroscopy in the
      biomedical and biophysical sciences. These centers include the Laboratory for
      Fluorescence Dynamics at the University of Illinois and the Center for
      Fluorescence Spectroscopy at the University of Maryland. Even in the absence of
      the sophisticated equipment necessary for carrying out the time-resolved
      experiments, a great deal of information can be obtained from steady-state
      fluorescence profiles if one is careful to monitor all of the available
      fluorescence observables, namely intensity, wavelength or color, and
      polarization. Steady-state measurements of ANS binding are also quite
      informative. The combination of kinetic as well as equilibrium approaches, as
      with folding studies using any technique, will provide further insight into the
      pathways and stable and transient intermediates in the folding and unfolding
      reactions. Fluorescence spectroscopy offers a very sensitive window into the
      structural and dynamic characteristics of macromolecules. Recent advances in data
      acquisition and analysis combined with available structure information from NMR
      and crystallographic studies have led to increasingly greater insight into the
      structural and dynamic determinants of fluorescence decay parameters in the
      native states of proteins. As our understanding of the fluorescence properties of
      native proteins has grown, fluorescence spectroscopists have begun to investigate
      what fluorescence can tell us about the denatured states of proteins as well as
      the folding/unfolding transitions and pathways. A great deal of progress has been
      made in the characterization and interpretation of the response of the various
      fluorescence parameters to protein folding and denaturation. There remain,
      however, a number of unanswered questions, particularly concerning the structural
      and dynamic determinants of the fluorescence properties of the denatured states
      of proteins. Future studies will undoubtedly be aimed toward this goal, and
      progress in this area will certainly result from systematic comparisons of
      fluorescence studies with a number of other biophysical and biochemical
      approaches.

PMID- 7633533
TI  - Ultraviolet absorption spectroscopy.

PMID- 7633534
TI  - Is it time for a pediatric health maintenance organization?

PMID- 7633535
TI  - Practice variations among pediatricians and family physicians in the management
      of otitis media.
AB  - OBJECTIVES: To determine theoretical practice patterns and Medicaid practices in
      the management of persistent and recurrent otitis media by family physicians and
      pediatricians in Colorado. METHODS: Members of the Colorado chapters of the
      American Academy of Pediatrics and the Colorado Academy of Family Medicine were
      surveyed with the use of two hypothetical case management scenarios for which
      they were asked to indicate which International Classification of Diseases, Ninth
      Revision, Medicaid codes they would use. Physicians were presented with two case
      scenarios (one involving a persistent asymptomatic middle ear effusion and the
      second involving recurrent otitis media) and were asked to choose from a variety
      of management options, including observation, antibiotic therapy, decongestants,
      corticosteroids, antibiotic prophylaxis, and referral for ventilation tube
      surgery. RESULTS: Family physicians would have prescribed high-cost antibiotics
      (amoxicillin plus clavulanate potassium, cefaclor, or cefixime) to treat
      persistent middle ear effusions twice as often as pediatricians would have (P <
      .002). At the 6-week visit, 50 family physicians (43%) would administer an oral
      decongestant either alone or in combination with other therapy as compared with
      16 (14%) of pediatricians (P < .001). Family physicians would refer patients for
      ventilating tube surgery three times more often than pediatricians at the 9-week
      visits (P < .001). Recurrent episodes of acute otitis media would be managed
      similarly by both physician groups. Respondents reported a wide variety of
      International Classification of Diseases, Ninth Revision, coding, often coding
      persistent effusions as acute otitis or as unspecified otitis media. CONCLUSIONS:
      The findings of this survey document the wide variation in practice patterns for
      treating children with persistent otitis media and children with recurrent otitis
      media in Colorado.

PMID- 7633536
TI  - Physician and parent opinions. Are children becoming pincushions from
      immunizations?
AB  - OBJECTIVE: To determine parent and physician opinions regarding the
      administration of multiple childhood immunizations by injection. DESIGN:
      Confidential mailed survey to physicians and residents; interview of parents
      during office visits for immunizations. PARTICIPANTS: Physicians and parents from
      Rochester, NY. RESULTS: The survey included 215 practicing physicians and 74
      residents; response rate was 82%. Of the 197 parents interviewed, 93% were
      mothers, 68% were white; the mean (+/- SD) age was 25.8 +/- 5.2 years, with 12.8
      +/- 1.8 years of education; 59% had private insurance, and 35% had Medicaid
      coverage. Of the parents, 31% had strong concerns about their child receiving a
      single injection; an additional 10% (total, 41% vs 31%; chi 2 = 4.05, P = .04)
      had the same concerns about their child receiving three injections. More
      practicing physicians than parents had strong concerns about children 7 months
      old or younger receiving three injections (60% vs 41%; chi 2 = 7.71, P < or =
      .01). Physician concern increased further when physicians were asked about
      administration of four injections (80% vs 60%; chi 2 = 18.77, P < .001). Of the
      parents, 64% preferred one rather than two visits to have three injections
      administered, if their physician recommended it; 58% still preferred one visit
      even if four injections were needed. CONCLUSIONS: Physicians have more concerns
      than parents about the administration of multiple injections at a single visit.
      Pain for the child was the main concern of all respondents. While most physicians
      have strong concerns about administering three or more injections at one visit,
      most parents prefer this practice. Continued education and reassurance of parents
      and physicians is needed to address concerns about children becoming
      "pincushions" from immunizations.

PMID- 7633538
TI  - Comparative neonatal morbidity of abdominal and vaginal deliveries after
      uncomplicated pregnancies.
AB  - OBJECTIVE: To determine whether the risk of cesarean section following
      uncomplicated pregnancies has been reduced by current obstetric practices by
      comparing the neonatal risk of vaginal deliveries with the risk incurred
      following abdominal delivery in otherwise uncomplicated pregnancies. DESIGN:
      Observational, cohort study. A subpopulation of 11,702 women without
      complications of pregnancy was identified from a perinatal database, classified
      by subsequent mode of delivery, and compared for neonatal morbidity. This
      analysis was repeated after the cesarean section group was further narrowed to
      include only "repeated elective" deliveries. SETTING: Low-risk inborn setting.
      Tertiary care (level III nursery) referral center and a community (level II
      nursery) hospital. INTERVENTION: Cesarean section performed electively, for
      cephalopelvic disproportion, or for failure to progress. OUTCOME VARIABLES:
      Chosen prior to data analysis: neonatal mortality and morbidity. RESULTS: Groups
      differed with regard to ethnicity and sex. Infants who were delivered by cesarean
      section were more likely to have 1-minute Apgar scores less than 4, require
      intermediate or intensive nursery care at admission (6.3% vs 1.3% [P < .001]),
      and require greater respiratory support (mechanical ventilation, 1.6% vs 0.3%;
      oxygen therapy, 4.9% vs 1.4%; or room air, 93.5% vs 98.4% [P < .001]) than
      infants who were delivered vaginally. Similar results were found when patients
      who were delivered vaginally and by repeated elective cesarean section were
      compared. CONCLUSION: Although reports have recently emerged suggesting
      otherwise, abdominal delivery following an uncomplicated pregnancy remains a risk
      factor for adverse neonatal outcome despite current obstetric practices.

PMID- 7633537
TI  - Sleep disturbances in children with atopic dermatitis.
AB  - OBJECTIVES: To test hypotheses based on clinical impressions that children with
      atopic dermatitis (AD) have frequent sleep-related problems, including difficulty
      falling asleep, night waking due to itching and scratching, and daytime symptoms
      of tiredness and irritability. DESIGN: Sleep habits and behaviors were assessed
      using the Child Sleep Behavior Scale (a 22-item Likert-type questionnaire for
      parents) in children with AD compared with normative data for age. Twelve
      questions were added to the questionnaire to address sleep-related habits
      relevant to night time pruritus, and to assess daytime behavioral symptoms of
      inadequate sleep. SETTING: Tertiary care center. PATIENTS: Fifty-nine children
      between ages 5 and 12 years meeting criteria for AD representing a referral
      population to a regional center. RESULTS: Compared with normative data, children
      with AD showed notable differences for nine of the 22 items on the sleep
      questionnaire, including the following: greater difficulty falling asleep,
      frequent night waking, less total sleep, and greater difficulty awakening for
      school. The children with AD also reported frequent daytime tiredness and
      irritability, and the severity of AD symptoms showed moderate correlations with
      sleep problems and with daytime behaviors suggestive of inadequate sleep.
      Difficulty falling asleep and night waking correlated with daytime behavior and
      discipline problems. CONCLUSIONS: Children with AD often have disrupted sleep and
      daytime behavioral difficulties associated with insufficient sleep. Improved
      sleep may be an important treatment focus in the clinical management of children
      with AD.

PMID- 7633539
TI  - Social support of inner-city fathers and mothers.
AB  - OBJECTIVE: To examine mutual support of inner-city parents and how it relates to
      the father's expected role as a parent. DESIGN: Cross-sectional study. SETTING:
      An urban teaching hospital in inner-city Baltimore, Md. PATIENTS OR OTHER
      PARTICIPANTS: Inner-city-dwelling parents whose neonates were born at an urban
      teaching hospital between March and May 1992. INTERVENTION: Data were collected
      through structured independent interviews with each parent during the neonate's
      hospitalization. MAIN OUTCOME MEASURES: General social support was assessed by
      Sarason's Social Support Questionnaire. Paternal involvement was defined as the
      father's expected accessibility, engagement in child-rearing tasks, and decision
      making responsibility during infancy. RESULTS: Most mothers and fathers cited the
      other parent as a source of general support. Most believed that the other parent
      would help and would not hinder them in their role as parent. For mothers, the
      father's expected accessibility, engagement, and decision-making responsibility
      was positively correlated with his general support. For the fathers, expected
      accessibility was positively related to general support from the mother. As
      parents' mutual support increased, so did concordance in their expectations of
      the father's role. CONCLUSIONS: Many inner-city parents do rely on each other.
      Pediatricians can promote shared parenting by recognizing and building on this
      mutual support.

PMID- 7633540
TI  - Resolution of middle ear effusion in newborns.
AB  - OBJECTIVES: To determine the natural history of middle ear effusion (MEE) in
      newborns and compare the results of pneumatic otoscopy with tympanometry and
      acoustic reflex measurements in the evaluation of the middle ear of neonates.
      DESIGN: A descriptive natural history study with comparison of three evaluation
      methods for MEE. SETTING: County hospital nursery and pediatric clinic.
      PARTICIPANTS: Sixty-eight full-term, healthy neonates were studied on day 1 of
      life; 65 on day 2; and 24 on day 3. Thirty-eight infants returned at 2 weeks of
      age, and from this group, 23 returned at 2 months of age. INTERVENTIONS: Two
      independent observers performed otoscopy. An audiologist performed tympanometry
      and ipsilateral acoustic reflex measurements. Infants were evaluated daily from
      birth by all three methods for up to 3 days. MAIN OUTCOME MEASURE: The time to
      resolution of MEE as determined by three methods. RESULTS: In the first 3 hours
      of life, all babies examined had MEE diagnosed in both ears. By the third day,
      MEE apparently had resolved in 73% of ears by otoscopy, 88% by acoustic reflex
      measurements, and 92% by tympanometry. At 2 weeks, MEE was present by otoscopy in
      13% (10/75 of ears). These were primarily newly acquired MEEs. Interobserver
      agreement by otoscopy as determined by kappa scores was moderate on days 1 and 3,
      poor on day 2, and excellent at 2 weeks and 2 months. CONCLUSIONS: Middle ear
      effusion diagnosed by otoscopy apparently resolves in 72 hours in most neonates.
      Interobserver agreement of otoscopists was excellent after babies were discharged
      from the nursery, suggesting that pneumatic otoscopy can be used to diagnose MEE
      in neonates this age. Most MEEs that are diagnosed 2 weeks and 2 months after
      birth are new and asymptomatic.

PMID- 7633541
TI  - Elevated environmental lead levels in a day care setting.
AB  - OBJECTIVE: To determine the risk of lead poisoning among children enrolled in day
      care centers with elevated environmental lead burdens. DESIGN: Survey. SETTING:
      Six day care centers on properties owned by a major state-supported university.
      PATIENTS AND OTHER PARTICIPANTS: One hundred fifty-five of 234 eligible children
      (mean age, 4.8 years) enrolled in these centers were screened by questionnaire
      for risk factors of lead exposures. Blood samples for lead levels were also
      obtained. Observations of day care activities relative to lead exposure risks
      were recorded. Analyses of lead levels in paint, dust, and/or soil samples at the
      six centers were obtained. MAIN OUTCOME MEASURES: Prevalence of elevated blood
      lead levels and associated behavioral risk factors for lead exposure in children
      attending day care centers. RESULTS: Elevated levels of lead in paint (2.4% to
      40% lead) were present in all day care facilities. Three day care centers had
      elevated lead levels in windowsill dust (62,000 to 180,000 micrograms [corrected]
      of lead per square meter) or soil (530 to 1100 mg of lead per kilogram):
      Questionnaires documented low risk for lead exposure to children in the home
      environments. Direct observations in the day care setting revealed optimal
      supervision and hygiene of the children. Blood lead levels were less than 0.5
      mumol/L (10 micrograms/dL) in all but one of the 155 children screened.
      CONCLUSIONS: Children attending day care centers with high environmental lead
      burdens need further documentation of blood lead levels, at-risk behaviors, and
      lead exposure risks in the home environments as an adjunct to the instigation of
      lead abatement procedures at the day care centers.

PMID- 7633543
TI  - Health status of pediatric refugees in Buffalo, NY.
AB  - OBJECTIVE: To characterize the health status of recent pediatric refugees.
      RESEARCH DESIGN: Medical records of 107 pediatric refugees who underwent
      screening during a recent 24-month period were reviewed. SETTING: A county
      hospital pediatric clinic in a metropolitan area with a population of 1,189,000.
      The majority of pediatric refugees who come to the Buffalo, NY, area receive a
      health screening in this clinic. RESULTS: Most of the children were from Vietnam
      (67%), the Soviet Republics (19%), or Africa (14%). The median age was 8 years 2
      months (range, 1 to 18 years). Only 39% of the children had evidence of adequate
      immunizations for age (39 of the children from Vietnam, two children from Africa,
      and one from the Soviet Republics). In 30%, physical examinations exposed
      conditions that required follow-up or referral to a medical or surgical
      specialist. Forty-two percent of the children required dental referral. Seven
      children were anemic; three had microcytic anemia. Of 81 children who underwent
      screening for hepatitis B, six (7%) were carriers, 35 (43%) were positive for
      hepatitis B surface antibody, and only four (5%) related a history of hepatitis
      exposure. Stool specimens were examined for ova and parasites in 87 children; 19
      had pathogenic parasites with multiple organisms in two. Thirteen (24%) of 55
      children who were tested from Vietnam, five (36%) of 14 children who were tested
      from Africa, and one (5%) of 18 children who were tested from the Soviet
      Republics had pathogenic parasites. Parasites included Ascaris lumbricoides (n =
      8), Necator americanus or Ancylostoma duodenale (n = 5), Giardia lamblia (n = 3),
      Trichuris trichiura (n = 2), Dientamoeba fragilis (n = 2), and Entamoeba
      histolytica (n = 1). Skin testing for tuberculosis with purified protein
      derivative (tuberculin) was completed in 83 children, and 17 (20%) had reactive
      tests (21% [12/58] from Vietnam, 11% [1/9] from Africa, and 25% [4/16] from the
      Soviet Republics). CONCLUSIONS: Refugee children who come to the United States
      frequently have conditions that put them at risk of future morbidity and may
      require utilization of substantial health care resources. Some of these
      conditions represent public health concerns.

PMID- 7633542
TI  - Sources of health care and health needs among children in kinship care.
AB  - OBJECTIVES: To determine the characteristics of children in kinship care and
      their caregivers who have access to health care (a single source of health care
      or a single provider), and to determine the relation between indicators of access
      and health needs. DESIGN: Cross-sectional. SETTING: A large eastern city.
      SUBJECTS: Two hundred ten children selected from households with children in
      kinship care in April 1989. METHODS: Data were obtained from medical records,
      access and demographic questionnaires, and a medical and psychologic evaluation.
      RESULTS: A single facility for health care was reported by 93% of the sample; two
      thirds of those identified one health care provider. One source of care or one
      provider was associated with variables such as young age at placement and medical
      assistance insurance. Children who did not have a single source of care were more
      likely to have unmet health needs (87% vs 61%, P < .05), especially unmet mental
      health needs (60% vs 31%, P < .05). CONCLUSIONS: Children in kinship care had
      good access to health care, but the level of unmet health needs was high.
      Children who did not have a single source of health care were more likely to have
      unmet health needs, especially unmet mental health needs. These findings have
      implications for future health care planning for children in out-of-home care.

PMID- 7633544
TI  - Pediatric asthma care in US emergency departments. Current practice in the
      context of the National Institutes of Health guidelines.
AB  - OBJECTIVES: To determine whether US emergency department care for pediatric
      asthma conforms to the National Institutes of Health guidelines and whether the
      guidelines are likely to be adopted in clinical practice. DESIGN: Mail survey
      conducted from January to April 1992, and stratified by hospital type
      (children's, public and community). SETTINGS: Emergency departments of US
      hospitals. PARTICIPANTS: Simple stratified random sample of emergency department
      directors from 376 sampled hospitals. MEASUREMENTS: Self-reported data on
      emergency department pediatric asthma care, and knowledge and attitudes about the
      National Institutes of Health guidelines. Data are reported as mean (+/- SE).
      RESULTS: Sixty-eight percent of the surveyed emergency department directors
      responded. During 1991, there were an estimated 1.6 million visits for pediatric
      asthma care. Asthma accounted for 16.9% (+/- 9.0%) of all pediatric emergency
      department visits. Only 2.1% (+/- 1.0%) reported the use of written protocols or
      guidelines, with significant variation by hospital type. Sixty-seven percent (+/-
      3.0%) reported the use of pulse oximetry. Eighty percent reported the use of beta
      agonists by inhalation as the initial treatment. Only 44.7% (+/- 2.9%) reported
      the use of steroids if there was a poor response to the initial treatment. An
      estimated 45.5% (+/- 3.9%) of respondents had heard of the guidelines at the time
      of this survey; approximately 24% reported that they had read the guidelines.
      Most respondents reported that the guidelines were credible, clear and concise,
      and likely to be adopted in their emergency department. CONCLUSIONS: These data
      suggest that reported pediatric asthma care in US emergency departments differs
      substantially from the National Institutes of Health guidelines, with
      considerable variation by hospital type. The guidelines appear to provide an
      acceptable tool for emergency departments to use in assessing their pediatric
      asthma care. However, in light of the lack of evidence that the guidelines will
      improve outcomes, the impact of national guideline adoption remains unclear.

PMID- 7633545
TI  - Effectiveness of computer-generated telephone messages in increasing clinic
      visits.
AB  - OBJECTIVE: To evaluate the effectiveness of computer-generated telephone reminder
      calls in increasing kept appointment rates in a public health setting. DESIGN:
      Randomized controlled trial. SETTING: Public health clinic, Georgia. PATIENTS:
      Five hundred seventeen clients with scheduled appointments during a 4-week period
      at immunization, women, infant, and children; well-child; or family-planning
      programs. INTERVENTION: A single computer-generated telephone reminder 1 day
      before each client's scheduled appointment. MAIN OUTCOME MEASURE: Rates of kept
      appointments. RESULTS: Of the 277 clients assigned to receive the intervention,
      144 (52%) kept their appointments, compared with only 78 (32.5%) of 240 who were
      not assigned to receive a message (P < .05). Improvement in kept appointment
      rates associated with receiving the message was highest for the immunization
      program (183% increase, P < .05), with increases of 64%, 53%, and 44% for the
      well-child; women, infant, and children; and family-planning programs,
      respectively. CONCLUSIONS: These results suggest a simple and effective method to
      increase kept appointment rates in a variety of public health programs.

PMID- 7633546
TI  - Injuries from falls on playgrounds. Effects of day care center regulation and
      enforcement.
AB  - OBJECTIVES: To measure the incidence of playground fall injuries among children
      attending licensed US day care centers and to evaluate how injury incidence
      varies with center characteristics and with the regulatory and enforcement
      climate in which centers operate. DESIGN: Telephone surveys of directors of day
      care centers and enforcement agencies and review of written day care regulations.
      SETTING: Probability sample of licensed day care centers in 50 states and the
      District of Columbia. PARTICIPANTS: Children attending day care centers with
      playgrounds. MAIN OUTCOME MEASURES: Medically attended playground fall injuries.
      RESULTS: Among the 1740 day care centers studied, a weighted total of 89.2
      injuries occurred during the 2-month study period (0.25/100,000 child-hours in
      day care). The most important risk factor for injury was height of the tallest
      piece of climbing equipment on the playground in both bivariate (P = .01) and
      multivariate (P = .02) analyses. Neither regulations addressing playground safety
      or playground surfaces nor enforcement patterns were associated with lower injury
      rates. CONCLUSIONS: Additional effort is needed to develop and evaluate
      regulations and enforcement that reduce injury risks for children while
      minimizing burden on day care centers. In the meantime, limiting climbing
      equipment heights may reduce playground injury rates.

PMID- 7633547
TI  - Teenage childbearing. An adaptive strategy for the socioeconomically
      disadvantaged or a strategy for adapting to socioeconomic disadvantage?
AB  - OBJECTIVE: To examine the relation between childbearing and educational and
      vocational achievements of American females high school students. DATA SOURCE:
      Articles published in English during the past decade about the educational,
      vocational, and socioeconomic sequelae of childbearing among female high school
      students. DATA SELECTION: Articles that did not contain data about the relation
      between adolescent childbearing and educational and vocational achievement were
      excluded. DATA SYNTHESIS: Most females who begin childbearing during adolescence
      obtain less schooling and poorer-paying jobs than do females who postpone
      childbearing. The reasons for this are elusive. Differences in the family and
      cultural backgrounds of early (high school-age) and later (18 years and older)
      childbearers explain some but not all of the association between early
      childbearing and educational and vocational underachievement. The effect of
      childbearing preferences on the educational and vocational achievements of
      teenagers has not been studied adequately. Lack of concrete information could
      result in underestimation of the effect of early childbearing on the
      socioeconomic well-being of young Americans, and create the impression that
      adolescent pregnancy is an adaptive response to urban poverty. CONCLUSIONS: As
      much as the long-term socioeconomic sequelae of adolescent childbearing reflect
      factors that influence the judgments young people make about the costs and
      benefits of contraception and parenthood, adolescent childbearing is a means of
      adapting to urban poverty. Thus postponing adolescent conceptions and parenthood
      may have a less important effect on the socioeconomic well-being of young
      Americans than expected.

PMID- 7633548
TI  - The pediatric clerkship director. Support systems, professional development, and
      academic credentials.
AB  - Since the advent of the clerkship at The Johns Hopkins Medical School in the late
      19th century, this model has been the backbone of clinical training for medical
      students throughout the world. Despite the pervasiveness of clerkships, little
      information exists about the faculty that oversees them administratively. We
      documented the reported academic credentials, professional development, and
      support systems for pediatric clerkship directors in the United States and
      Canada. Our findings should be useful to clerkship directors and department
      chairpersons across disciplines.

PMID- 7633549
TI  - Radiological case of the month. Coarctation of the aorta.

PMID- 7633551
TI  - Pathological case of the month. Fatal hemorrhagic staphylococcal pneumonia.

PMID- 7633550
TI  - Picture of the month. Juvenile pityriasis rubra pilaris.

PMID- 7633552
TI  - Physicians' attitudes toward a pediatric notification program of transfusion
      related human immunodeficiency virus risk.

PMID- 7633553
TI  - Corticosteroid therapy for Pneumocystis carinii pneumonia in children with human
      immunodeficiency virus infection.

PMID- 7633554
TI  - [Use of ipratropium bromide by inhalation in the treatment of acute asthma in
      children. Clinical experience].
AB  - Clinical experience. Anticholinergic drugs, notably atropine, have long been
      known to be potent bronchodilators, but their use was limited by systemic
      absorption and significant side effects. Ipratropium bromide has no systemic
      anticholinergic action, but maintains the local anticholinergic action on the
      tracheobronchial tree. In 1984, we observed that in children with acute asthma,
      treated aggressively with frequent doses of nebulized beta 2 adrenergics, a
      significant degree of airway obstruction remained, and did not improve with
      further doses of beta 2 agonists. We postulated that vagal bronchomotor tone
      might contribute to this problem and that further improvement could be obtained
      with the use of ipratropium bromide. Ipratropium was shown to be useful in
      pediatric asthma in the early 1980s. There appeared to be an age difference in
      the response to the medication. A dose-response curve for nebulized ipratropium
      was determined. The optimal dose was found to be > 75 micrograms. Repeated
      studies and extensive experience demonstrated safety and few side effects. In
      1984 we studied the effect of adding ipratropium after one hour of treatment with
      a regimen of frequent nebulized salbutamol in children with acute asthma. We
      found a slight but significant further improvement in FEV1, beginning one hour
      after administration of ipratropium. Further studies confirmed these findings,
      when using two doses of combined ipratropium/fenoterol an hour apart or every 40
      minutes for three doses. One study using ipratropium every eight hours failed to
      show a change, confirming the need to use the medication more frequently. For the
      past six years, we have been using a protocol that incorporates ipratropium in
      the treatment of acute asthma in children. (ABSTRACT TRINCATED AT 250 WORDS)

PMID- 7633555
TI  - [Role of Bronchodual in the long-term treatment of asthma in children].
AB  - Bronchodual is a combination of two bronchodilators, a beta-2 adrenergic
      substance (fenoterol, 50 micrograms per dose), and an anticholinergic substance
      (ipratropium bromide, 20 micrograms per dose), administered by metered aerosol.
      According to different studies carried out with adults and children, the
      bronchodilating action of this combination is greatly superior to that obtained
      with each substance individually; the beta-2 adrenergic substance can be spared;
      its action is longer and involves a decrease in the number of drug intake and
      lastly its tolerance is excellent. A French multicentre study was performed with
      74 children (7 to 15 years old, mean: 11.8 +/- 2.6 years), 53 boys and 21 girls
      with allergic or non-allergic asthma: 41 children presented a moderate asthma
      (one crisis per month) and 33 children moderately severe asthma (one crisis per
      week). These children had been given no corticosteroid therapy (per os or
      inhaled) for at least 15 days, their usual long-term treatment (cromoglycate,
      anti H1, theophylline LP, antibiotics) was given as normal. Their FVC was > or =
      80% of predicted values and they presented an intercritical airway obstruction.
      Hypoxemia was noted in 41.2% of the children. A reversibility test was performed
      with Bronchodual: 68 of 74 children (i.e. 91.9%) were responders, ie after two
      doses of Bronchodual at least one of the FEFs had increased by at least 15% when
      compared with the initial values. The responders were given a 2 month treatment
      with two inhalations 3 times/day with a spacer. Fifty-seven patients were
      considered for the final evaluation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7633556
TI  - [Role of anticholinergic agents in the treatment of cystic fibrosis].
AB  - A significant proportion of patients with cystic fibrosis (CF) demonstrate
      increased airways hyperreactivity, a feature that has been well documented by
      several authors. This bronchial lability is more pronounced in those with more
      severe and advanced lung disease. Several mechanisms for this increased airways
      responsiveness have been proposed such as chronic inflammation with impairment of
      mucosal permeability, increase in amount of bronchial secretions, systemic
      autonomic abnormality, increase in incidence of atopy and airway narrowing and
      changes in airway geometry induced by chronic inflammation. Several studies have
      assessed the change in FEV1 after beta-agonist or anticholinergic therapy in CF
      patients and there are studies in which the effect of the combination of drugs
      was tested. In a group of young CF patients, we found on average a 7% increase in
      FEV1 after salbutamol and a 10% improvement after ipratropium bromide (IB). After
      inhaling both drugs, there was a 17% increase in FEV1 from baseline. There were
      also significant changes in static volumes and airway-resistance measurements
      when salbutamol and IB were administered in combination. The influence of
      pretreatment of either normal saline, salbutamol or ipratropium bromide with
      methacholine was evaluated by Avital and co-workers in a double-blind crossover
      study. They found an increase in PC20 without a change in baseline FEV1 following
      salbutamol and an even greater change after IB. These results suggest that the
      adrenergic agent altered the smooth muscle contractile mechanism, and that
      muscarinic pathway appears to be important in the pathogenesis of expiratory
      airflow obstruction in some CF patients. The mechanisms of this cholinergic
      sensitivity are unclear.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7633557
TI  - [Role of anticholinergic agents in acute bronchiolitis in infants].
AB  - There is almost universal agreement that neither beta 2-agonists, theophyllin nor
      steroids, given either by inhalation or systemically, have any effect on lung
      function in acute bronchiolitis of infancy. As ipratropium bromide appears to be
      a more effective bronchodilator drug than beta 2-stimulants in the first year of
      life, a study was set up to investigate its possible role in bronchiolitis.
      Diagnostic requirements for inclusion in the study were tachypnoea,
      hyperinflation recession, and the presence of fine crepitations on auscultation
      with a chest X-ray which excluded either heart failure or gross pneumonia. Twenty
      five infants were recruited in the preliminary study. A respiratory jacket and
      water filled oesophageal catheter (feeding tube) were used to measure the work of
      breathing per minute and per litre of expired gases. After baseline readings the
      infants received salbutamol (2.5 mg), ipratropium bromide (250 micrograms) or
      placebo in 2 ml volumes using a standard nebuliser. The salbutamol and water were
      associated with an increase in the work of breathing of 4% and 22% respectively.
      The ipratropium therapy led to a fall of 18% with a significant response in 6 of
      15 infants studied. Following these encouraging results, a double blind study was
      set up assessing the effects of nebulised ipratropium bromide (250 micrograms)
      and nebulised saline given every 6 hours to 66 infants admitted to the ward with
      acute bronchiolitis. Response to therapy was determined using symptom scores and
      need for nebulised therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7633558
TI  - [Physiological basis for the use of muscarine antagonists in bronchopulmonary
      dysplasia].
AB  - The rationale for the use of muscarinic antagonists in bronchopulmonary dysplasia
      (BPD) is based on the physiology and pharmacology of airway smooth muscle, the
      pathology of BPD, and the response of infants with BPD to bronchodilators, in
      vivo and in vitro studies of airway smooth muscle of newborn animals and humans
      indicate that vagal efferent airway innervation and/or muscarinic receptors are
      functional at birth, as well as early in gestation. Current concepts regarding
      muscarinic receptor subtypes suggest that M3 receptors mediate airway smooth
      muscle contraction, M2 receptors are autoinhibitory and limit vagally-mediated
      bronchoconstriction, and M1 receptors may play a facilitatory role in ganglionic
      transmission. Muscarinic receptor subtypes appear to be functionally expressed at
      birth but may undergo developmental regulation. Infants with BPD have an elevated
      pulmonary resistance that is accompanied by hypertrophy of airway smooth muscle,
      b2-agonists cause bronchodilation in BPD as does atropine in infants recovering
      from severe BPD. The synthetic congener of atropine, ipratropium bromide (IPB)
      causes bronchodilation in ventilator-dependent infants with BPD in a dose
      dependent fashion. Nebulized IPB causes a decrease in respiratory resistance that
      reaches a maximum of 20% at 175 mg. The bronchodilation seen with muscarinic
      antagonists suggests that part of the elevated resistance associated with BPD is
      due to increased muscarinic tone, presumably vagal in origin. When IPB is
      combined with salbutamol (0.04 mg) the response is increased in magnitude and
      duration; reaching a slightly larger decreases in resistance (26%) that is now
      accompanied by an increase in compliance (20%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7633559
TI  - Inhibitory effect of a hydrophilic alpha-tocopherol analogue, MDL 74,405, on
      generation of free radicals in stunned myocardium in dogs.
AB  - A previous study has demonstrated that the hydrophilic (alpha-tocopherol
      analogue, MDL 74,405, attenuates postischemic myocardial dysfunction ("stunning")
      in dogs. The present study was undertaken to determine directly whether the
      salutary effect of this drug on myocardial stunning results from inhibition of
      the generation of oxygen-derived free radicals. Open-chest dogs undergoing a 15
      min coronary artery occlusion and 3 h of reperfusion received an intravenous
      infusion of either saline (controls, n = 7) or MDL 74,405 (n = 6) starting 30 min
      before coronary occlusion and ending 60 min after reflow at a dose of 0.3
      mg/kg/h. To measure free radical production, all dogs received an intravenous
      infusion of the spin trap alpha-phenyl N-tert-butyl nitrone (PBN) and local
      coronary venous plasma was analyzed by electron paramagnetic resonance (EPR). In
      control dogs, the myocardial production of PBN adducts exhibited an initial burst
      immediately after the onset of reflow and remained elevated until 10 min after
      reperfusion. Dogs treated with MDL 74,405 demonstrated a marked decrease in PBN
      adduct production. This effect of MDL 74,405 could not be attributed to
      nonspecific factors such as differences in ischemic zone size, collateral flow,
      arterial pressure, heart rate, coronary flow or other hemodynamic variables.
      These results demonstrate that the hydrophilic vitamin E analogue, MDL 74,405,
      inhibits free radical generation after myocardial ischemia-reperfusion in vivo.
      This finding provides direct evidence that the salutary effects of MDL 74,405 on
      myocardial stunning are due to attenuation of oxidative stress.

PMID- 7633560
TI  - Status of antioxidants in brain microvessels of monkey and rat.
AB  - Levels of certain antioxidants namely reduced glutathione (GSH), ascorbic acid
      (Vit C), alpha-tocopherol (Vit E) and antioxidant enzymes, superoxide dismutase
      (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase
      (GR) were compared in monkey and rat brain microvessels which constitute the
      blood-brain barrier (BBB). The BBB of both the species contains appreciable
      amounts of the antioxidants to protect against oxidative damage. The level of
      protection in rat seems to be more efficient than monkey since rat microvessels
      contain higher concentrations of some of the bio-antioxidants. The comparative
      status of enzymatic and non-enzymatic protective system against oxidation in the
      brain microvessels has been discussed.

PMID- 7633561
TI  - Antioxidant properties of phenyl styryl ketones.
AB  - Phenolic and non phenolic derivatives of phenyl styryl ketones were synthesized
      and evaluated as in vitro inhibitors of iron and cumene hydroperoxide dependent
      lipid peroxidation in rat brain homogenates. The compounds were also tested for
      antioxidant activity in phosphatidylcholine liposomes. Phenyl 3,5-di-tert-butyl-4
      hydroxystyryl ketone was found to be the most potent inhibitor of peroxidation
      among all the compounds tested. It was found to be more active than vitamin E. It
      also reduced the stable free radical 1,1-diphenyl-2-picrylhydrazyl to an
      appreciable extent.

PMID- 7633562
TI  - NADPH-cytochrome-P450 reductase promotes hydroxyl radical production by the iron
      complex of ADR-925, the hydrolysis product of ICRF-187 (dexrazoxane).
AB  - ICRF-187 (dexrazoxane) is currently in clinical trials as a cardioprotective
      agent for the prevention of doxorubicin-induced cardiotoxicity. ICRF-187 likely
      acts through its strongly metal ion-binding rings-opened hydrolysis product ADR
      925 by removing iron from its complex with doxorubicin or by chelating free iron.
      The ability of NADPH-cytochrome-P450 reductase to promote hydroxyl radical
      formation by iron complexes of ADR-925 and EDTA was compared by EPR spin
      trapping. The iron-EDTA complex produced hydroxyl radicals at six times the rate
      that the iron-ADR-925 complex did. The aerobic oxidation of ferrous complexes of
      ADR-925, its tetraacid analog, EDTA and DTPA was followed spectrophotometrically.
      The iron(II)-ADR-925 complex was aerobically oxidized 700 times slower than was
      the EDTA complex. It is concluded that even though ADR-925 does not completely
      eliminate iron-based hydroxyl radical production, it likely protects by
      preventing site-specific hydroxyl radical damage by the iron-doxorubicin complex.

PMID- 7633563
TI  - Oxidatively modified plasma phospholipids containing reactive carbonyl functions
      measured by HPLC: evidence for phosphatidylcholine-bound aldehydes in plasma of
      burn patients.
AB  - A HPLC method has been developed to measure phosphatidylcholine (PC) containing
      reactive carbonyl functions in the sn-acyl residue in order to study processes in
      which such reactive carbonyls can be formed due to e.g. oxidative fragmentation.
      The method has been applied to determine PC-bound carbonyls as 2,4
      dinitrophenylhydrazones (DNPH) in plasma of burn patients. Plasma from healthy
      volunteers served as controls. Additionally, in vitro oxidation experiments (A:
      plasma, buffer diluted; B: plasma + iron-EDTA complex and C: plasma + iron-EDTA
      complex + H2O2) have been performed to obtain and to identify 2,4
      dinitrophenylhydrazine derivatizable carbonyl functions in plasma PC. Both, the
      PC-aldehydes and PC-aldehyde DNPH derivatives were cleavable with phospholipase
      C. Quantification was based on thin-layer chromatography purified soybean
      phosphatidylcholine, which was identically oxidized and derivatized as the plasma
      lipids in vitro.

PMID- 7633564
TI  - The use of quantified maximum entropy methods for optimising information from
      electron paramagnetic resonance spectroscopy.
AB  - A quantified maximum entropy method is applied to the optimisation of analytical
      information from EPR spectra of free radicals. Statistically meaningful errors
      are produced for the positions and intensities of all spectral peaks and
      considerable improvements in sensitivity compared with conventional spectral
      enhancement procedures are obtained with measurements of the intensities of
      spectra of known radicals.

PMID- 7633565
TI  - The oxidation of phenol by ferrate(VI) and ferrate(V). A pulse radiolysis and
      stopped-flow study.
AB  - Potassium ferrate, K2FeO4, is found to oxidize phenol in aqueous solution (5.5 <
      or = pH < or = 10) by a process which is second order in both reactants; 
      d[FeVI]/dt=k1[FeVI][phenol], k1 = 10(7)M-1s-1. Product analysis by HPLC showed a
      mixture of hydroxylated products, principally paraquinone, and biphenols that
      indicate that oxidation of phenol occurs by both one-electron and two-electron
      pathways. The two-electron oxidant, producing both para- and ortho-hydroxylated
      phenols is considered to be ferrate(V) which is itself produced by the initial
      one-electron reduction of ferrate(VI). The rate of ferrate(V) reaction with
      phenol was determined by pre-mix stopped flow pulse-radiolysis and found to be k7
      = (3.8 +/- 0.4) x 10(5)M-1s-1.

PMID- 7633566
TI  - Mutual contact of adherent polymorphonuclear leukocytes inhibits their generation
      of superoxide.
AB  - Superoxide generation by polymorphonuclear leukocytes (PMNs) in suspension, or
      adherent to glass or plastic, after stimulation with N-formylmethionyl-leucyl
      phenylalanine or phorbol myristate acetate was measured by cytochrome c reduction
      and spin trapping. Amounts of superoxide generated by adherent PMNs were
      inversely related to cell density. The generation of hydrogen peroxide was also
      inhibited at higher cell densities. In contrast to adherent cells, superoxide
      released by PMNs in suspension linearly increased with respect to cell number
      over a wider range. Microscopic observation indicated that the number of cells in
      mutual contact increased rapidly at cell densities higher than 4 x 10(4)
      cells/cm2, and inhibition of superoxide became apparent at higher cell densities.
      Mediators which could be released by PMNs, such as NO and adenosine, were not the
      cause of inhibition. These data suggest that mutual contact of PMNs suppresses
      their generation of superoxide. Survival rates of PMNs after stimulation
      increased at higher densities, indicating that the mutual contact-induced
      inhibition of superoxide generation by PMNs may be physiologically relevant at
      sites of inflammation.

PMID- 7633567
TI  - The relative antioxidant activities of plant-derived polyphenolic flavonoids.
AB  - The relative antioxidant activities, against radicals generated in the aqueous
      phase, of a range of plant-derived polyphenolic flavonoids, constituents of
      fruit, vegetables, tea and wine, have been assessed. The results show that
      compounds such as quercetin and cyanidin, with 3',4' dihydroxy substituents in
      the B ring and conjugation between the A and B rings, have antioxidant potentials
      four times that of Trolox, the vitamin E analogue. Removing the ortho-dihydroxy
      substitution, as in kaempferol, or the potential for electron delocalisation by
      reducing the 2,3 double bond in the C ring, as in catechin and epicatechin,
      decreases the antioxidant activity by more than 50%, but these structures are
      still more effective than alpha-tocopherol or ascorbate. The relative
      significance of the positions and extents of hydroxylation of the A and B rings
      to the total antioxidant activity of these plant polyphenolics is demonstrated.

PMID- 7633568
TI  - Redox regulation of programmed cell death in lymphocytes.
AB  - A redox imbalance caused by an over-production of prooxidants or a decrease in
      antioxidants seems to play a role in the programmed cell death that occurs in
      various developmental programs. Such a physiological function for oxidative
      stress is particularly applicable to the immune system, wherein individual
      lymphocytes undergo continuous scrutiny to determine if they should be preserved
      or programmed to die. Following activation, lymphocytes produced increased levels
      of reactive oxygen species (ROS) which may serve as intracellular signaling
      molecules. The ultimate outcome of this increased ROS formation, i.e., lymphocyte
      proliferation versus programmed cell death, may be dictated by macrophage-derived
      costimulatory molecules that bolster or diminish lymphocyte antioxidant defenses.
      HIV-1-infected individuals display multiple symptoms of redox imbalance
      consistent with their being in oxidative stress, and lymphocytes from such
      individuals are more prone to undergo apoptosis in vitro. It is suggested that
      oxidative stress, and lymphocytes from such individuals are more prone to undergo
      apoptosis in vitro. It is suggested that oxidative stress is a physiological
      mediator of programmed cell death in lymphoid cells, and that HIV disease
      represents an extreme case of what can happen when regulatory safeguards are
      compromised.

PMID- 7633570
TI  - Peroxyl radical scavenging activities of hamamelitannin in chemical and
      biological systems.
AB  - The antioxidative activities of hamamelitannin (2',5-di-O-galloyl-hamamelose),
      gallic acid and dl-alpha-tocopherol against lipid peroxyl radicals were evaluated
      in chemical and biological systems. The peroxyl radical scavenging activity was
      evaluated by electron spin resonance (ESR) method in which both spin-trapping and
      direct reaction methods were used. In the spin-trapping method, as evaluated by
      50% inhibition concentration (IC50) of peroxyl radicals generated in a t
      butylhydroperoxide-methemoglobin system, hamamelitannin (IC50 = 95.3 +/- 2.7
      microM) showed the highest activity, followed by gallic acid (IC50 = 152.8 +/-
      14.6 microM) and dl-alpha-tocopherol (IC50 = 221.5 +/- 4.6 microM) as a positive
      control. When estimating by the direct method, IC50 values of hamamelitannin,
      gallic acid and dl-alpha-tocopherol were 93.5 +/- 2.1 microM, 141.6 +/- 2.0
      microM and 1590.0 +/- 330.0 microM, respectively. On peroxidation of lipid
      bilayers induced by 2,2'-azobis-(2-amidinopropane) dihydrochloride (AAPH) in
      terms of inhibition period (tinh), hamamelitannin showed the longest tinh time
      (1107.0 +/- 38.18 sec), followed by those of dl-alpha-tocopherol (877.5 +/- 31.8
      sec) and gallic acid (771.0 +/- 4.2 sec). The kinetic chain length, defined as
      the propagation numbers of a lipid peroxyl radical, and calculated from the ratio
      (Rp/Ri) of the rate of lipid peroxidation to that of inhibition by dl-alpha
      tocopherol, hamamelitannin and gallic acid were 27.23, 7.86 and 7.09,
      respectively. The effects of hamamelitannin, gallic acid and dl-alpha-tocopherol
      were evaluated on murine fibroblasts exposed to t-butylhydroperoxide (BHP) in
      terms of the cell survivals. In the protection, hamamelitannin induced the
      highest survival of 27.6 +/- 0.6% at 50 microM, while both gallic acid and dl
      alpha-tocopherol were less active at the same concentrations. On the basis of the
      results, hamamelitannin was concluded to have a high protective activity on cell
      damage induced by peroxides.

PMID- 7633569
TI  - EDTA differentially and incompletely inhibits components of prolonged cell
      mediated oxidation of low-density lipoprotein.
AB  - The extent to which cells can oxidize LDL may be underestimated because of the
      use of standard and arbitrary 24 hour in vitro incubations of cells with LDL.
      Such incubations have resulted in inconsistent results regarding the ability of
      cell-mediated LDL oxidation to generate relatively advanced oxidation products
      such as 7-ketocholesterol (7-KC). We studied prolonged oxidation of low density
      lipoprotein (LDL) by mouse peritoneal macrophages using HPLC measurement of
      cholesterol, cholesteryl esters and their oxidation products 7-KC and cholesteryl
      linoleate hydroperoxide (CL-OOH). Cell-mediated oxidation in Ham's F10
      consistently followed the successive stages previously described during 24 hour
      10 microM copper-mediated LDL oxidation, always generating 7-KC if allowed to
      proceed for sufficient time. The degree of inhibition of LDL oxidation achieved
      by metal chelators EDTA and DTPA at more advanced stages of cell-mediated LDL
      oxidation was not predictable from the published effects of such chelators upon
      early stages of metal-mediated and cell-mediated LDL oxidation. EDTA and DTPA
      only incompletely prevented the consumption of cholesteryl esters and the loss of
      performed CL-OOH when added after cell-mediated LDL oxidation was established,
      while effectively concurrently inhibiting the generation of 7-KC. These data
      indicate that progressive cell-mediated peroxidation of LDL cholesteryl esters
      and decomposition of CL-OOH may be less dependent upon a continuing supply of
      redox active metals than is the generation of 7-KC. In addition, they confirm the
      plausibility of prolonged cell-mediated oxidation of LDL as a source of
      oxysterols found in human atherosclerotic plaque, and imply that active redox
      cycling of metals is particularly important for their generation in vivo.

PMID- 7633571
TI  - Inhibition of stimulus-specific neutrophil superoxide generation by alpha
      tocopherol.
AB  - Alpha-tocopherol but not 2-carboxy-2,5,7,8-tetramethyl-6-chromanol (trolox or
      CTMC) and 2,2,5,7,8 pentamethyl-6-hydroxy chromane (PMC), derivatives of alpha
      tocopherol, inhibited the superoxide (O2-.) generation of rat peritoneal
      neutrophils (RPMN) induced by phorbol 12-myrisate 13-acetate (PMA). ID50 for
      neutrophils obtained from the peritoneal cavity of rat and guinea pig was about
      1microM. This concentration, however, was much lower than that for the inhibition
      of PMA-activated phospholipid-dependent protein kinase (PKC) (ID50 = 30 microM).
      The alpha-tocopherol sensitive O2-. generation was also observed in neutrophils
      induced by dioctanoylglycerol (diC8) and calcium ionophore A23187 but not by
      formylmethionyl-leucyl-phenylalanine (FMLP), opsonized zymosan (OZ) and sodium
      dodecyl sulfate (SDS). The pattern of inhibition by alpha-tocopherol was quite
      similar to that of staurosporine, a specific inhibitor of PKC. The alpha
      tocopherol content of RPMN was 12 ng/10(6) cells and a linear increase to 200
      ng/10(6) cells by addition of alpha-tocopherol to the cell suspension
      corresponded with an increased inhibition of O2-. generation. These results
      indicate that both the chemical structure and the content of alpha-tocopherol
      might be important factors in O2-. generation by neutrophils.

PMID- 7633572
TI  - Detection of aldehydes and their conjugated hydroperoxydiene precursors in
      thermally-stressed culinary oils and fats: investigations using high resolution
      proton NMR spectroscopy.
AB  - High field (400 and 600 MHz) proton NMR spectroscopy has been employed to
      investigate the thermally-induced autoxidation of glycerol-bound polyunsaturated
      fatty acids present in intact culinary frying oils and fats. Heating of these
      materials at 180 degrees C for periods of 30, 60 and 90 min. generated a variety
      of peroxidation products, notably aldehydes (alkanals, trans-2-alkenals and alka
      2,4-dienals) and their conjugated hydroperoxydiene precursors. Since such
      aldehydes appear to be absorbed into the systemic circulation from the gut in
      vivo, the toxicological significance of their production during standard frying
      practices is discussed.

PMID- 7633574
TI  - Purification, N-terminal amino acid sequence and partial characterization of a
      Cu,Zn superoxide dismutase from the pathogenic fungus Aspergillus fumigatus.
AB  - A superoxide dismutase (SOD) has been purified to homogeneity from the fungal
      pathogen Aspergillus fumigatus using a combination of cell homogenization,
      isoelectric focusing and gel filtration FPLC. The N-terminal amino acid sequence
      of the purified enzyme demonstrated substantial homology to known Cu,Zn
      superoxide dismutases for a range of organisms, including Neurospora crassa and
      Saccharomyces cerevisiae. The enzyme subunit has a pI of 5.9, a relative
      molecular mass of 19 kDa and a spectral absorbance maximum of 550nm. The non
      reduced enzyme has a relative molecular mass of 95 kDa. The enzyme remained
      active after prolonged incubation at 70 degrees C and was pH insensitive in the
      range 7-11. Potassium cyanide and diethyldithiocarbamate, known Cu,Zn SOD
      inhibitors, caused inhibition of the purified enzyme at working concentrations of
      0.25 mM, whilst sodium azide and o-phenanthroline demonstrated inhibition at
      higher concentrations (10-30 mM). SOD activity was also detectable in culture
      filtrate of A. fumigatus. This enzyme may have a potential role as a virulence
      factor in the avoidance of neutrophil and phagocyte oxidative burst killing
      mechanisms.

PMID- 7633573
TI  - Cell damage in inflammatory and infectious sites might involve a coordinated
      "cross-talk" among oxidants, microbial haemolysins and ampiphiles, cationic
      proteins, phospholipases, fatty acids, proteinases and cytokines (an overview).

PMID- 7633575
TI  - Upregulation of respiratory burst of polymorphonuclear leukocytes by a bleomycin
      derivative, peplomycin.
AB  - The influence of peplomycin (PLM) on the respiratory burst of peripheral blood
      polymorphonuclear leukocytes (PMN) was investigated. Short-term (5 min) treatment
      of human PMN with 0.1mu g/ml to 100mu g/ml of PLM increased phorbol myristate
      acetate (PMA)- and formyl-methionyl-leucyl-phenylalanine (FMLP)-induced luminol
      dependent chemiluminescence. PMN, as well as alveolar macrophages from rabbits
      treated with 0.5 to 1.0 mg/kg of peplomycin per day for 5 days, generated more
      superoxide (O2-) than the cells from untreated rabbits. In both PLM-treated and
      untreated PMN, chemiluminescence induced by FMLP and PMA was decreased to less
      than 50% of the control by staurosporine, superoxide dismutase (SOD) and
      catalase. However, the peak intensity in PLM-untreated PMN was decreased to about
      30% of the control by genistein, while this agent induced a slight decrease in
      peak intensity in the PLM-treated PMN. Inositol triphosphate and diacyl glycerol
      levels were not clearly increased by PLM, but an increase of intracellular Ca++
      and a shift of protein kinase C (PKC) to the membrane occurred in PMN within 1
      min after PLM treatment. Western blotting revealed that the tyrosine
      phosphorylation of a 115 kDa protein was upregulated by 5 to 50mu g/ml of PLM.
      While, PLM suppressed SOD activity in alveolar macrophages and PMN. These results
      seem to indicate that PLM increases the respiratory burst of PMN and macrophages
      both by way of direct PKC activation and by the upregulation of protein tyrosine
      phosphorylation. This increased reactive oxygen generation, together with the
      suppression of SOD activity seems to be tissue-impairing.

PMID- 7633576
TI  - Effect of parenteral antioxidants on adrenal pathobiology and leukocytes in
      hyperammonaemic toxaemia.
AB  - Infestation of sheep by L. cuprina larvae produces extensive skin wounds, severe
      dermatitis, hyperammonaemia and stress with adrenal necrosis and haemmorhage. In
      infested sheep, intramuscular (im) injections of Dl-Alpha tocopherol induced wool
      shedding and Desferrioxamine im prevented declines in white blood cells (WBC). In
      further trials, daily im injections of sodium ascorbate with Dl-alpha tocopherol,
      desferrioxamine and oral butylated-hydroxyanisole prevented adrenal damage and
      induced adrenocortical hypertrophy of the zona fasciculata. The treatment boosted
      the levels of mature and juvenile neutrophils, and blood glucose. Increases in
      toxic ammonia levels were correlated with increased toxic and band neutrophils,
      and globulin levels in treated sheep and toxic neutrophils in non-treated sheep.
      Decreases in serum zinc were correlated with declining lymphocytes and globulin
      levels. The results suggested that antioxidants protect and enhance adrenal
      activation in hyperammonaemic toxaemia. The changes in WBC, globulins and glucose
      were consistent with protected adrenocortical activation.

PMID- 7633577
TI  - Ibuprofen protects rat livers from oxygen-derived free radical-mediated injury
      after tourniquet shock.
AB  - Rats subjected to tourniquet shock suffer a severe form of circulatory shock,
      tissue and organ oxidative stress, and final multiple system organ failure (MSOF)
      and death of the animals within 24 h of tourniquet release. The oxidative damage
      observed in hind-limb muscle tissue after reperfusion does not by itself account
      for the final systemic and lethal MSOF. We have postulated that organ failure has
      its genesis in a primary perfusion abnormality, e.g. the hind limbs, which is
      followed by secondary hypoperfusion of other organs, such as the liver, as has
      been shown to be the case in several septic shock models. It has also been shown
      that injured or necrotic tissue can activate neutrophils, Kupffer cells,
      platelets, and both the complement and coagulation cascades. In turn, complement
      activation also leads to neutrophil and Kupffer cell activation as assessed by
      their capacity to generate oxyradicals. Herein we have evaluated the potential
      protective effect of ibuprofen on hepatic oxygen-derived free radical production,
      as well as its effects on both polymorphonuclear leucocyte (PMN) activation and
      liver infiltration. The protective effect of ibuprofen on hepatic oxidative
      injury was assessed by determining total thiol groups (SH), thiobarbituric acid
      reactive substances (TBARS), and by the release of aspartic acid (AsT) and
      alanine (AIT) aminotransferases in control animals, in animals subjected to 5 h
      of tourniquets, and in animals after 2 h of hind-limb reperfusion. Liver
      infiltration by PMNs was determined by histology after staining with eosin
      hematoxylin, and PMN activation by their capacity to reduce nitro blue
      tetrazolium (NBT).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7633578
TI  - The oxidation of amino acids by ferrate(V). A pre-mix pulse radiolysis study.
AB  - The forms of ferrate(V) which are derived from the one-electron reduction of
      potassium ferrate (K2FeO4) by ethanol radicals react with representative amino
      acids (glycine, methionine, phenylalanine and serine) at rates that are greater
      than 10(5)M-1s-1 near pH 10. The predominant interaction in the alkaline pH range
      is between the protonated ferrate(V) species, HFeO4(2-), and the amino acid
      anion. Fe(V) + amino acid-->Fe(III) + NH3 + alpha-keto acid The rate-determining
      process is the two electron reduction of ferrate(V) to iron(III) with oxidation
      and subsequent deamination of the amino acid. The reaction appears to involve an
      entry of the amino acid into the inner coordination sphere of ferrate(V). In all
      cases, ferrate(V) exhibits preferred attack on the amino group in contrast to the
      OH radical which attacks the thioether site of methionine and the phenyl ring of
      phenylalanine.

PMID- 7633579
TI  - Peroneus longus tendon tears: acute and chronic.
AB  - Tear of the peroneus longus tendon can be difficult to diagnose and treat.
      Fourteen cases of clinically proven tears are reported. Patients ranged in age
      from 31 to 63 years. There were 10 men and four women. The onset of symptoms was
      acute in eight cases. Chronic onset with slowly increasing pain occurred in six
      cases. Despite acute onset of symptoms, only one patient was diagnosed within 2
      weeks of his injury. The others had symptom duration ranging from 7 to 48 months.
      Twelve tears were located distally as the tendon turned into the cuboid groove.
      As os peroneum visible on x-ray was present in six cases, absent in seven cases,
      and cartilaginous in one case. The os peroneum was involved in the tear in three
      cases. Excision of part or all of the os peroneum was performed in four cases
      with a bridging tendon graft required in one case. A plantaris tendon graft was
      required in one case in which an os peroneum was absent. Patients with acute
      onset of symptoms tended to fare better than those with chronic onset of
      symptoms, regardless of the length of time from onset to time of surgery.
      Associated pathology in the peroneus brevis tendon was common, occurring in nine
      cases. These patients seemed to have a better surgical outcome than those with
      only a tear of the peroneus longus tendon. Associated findings affected diagnosis
      by masking symptoms but did not alter the outcome of treatment.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7633580
TI  - Histology and histomorphometric analysis of the normal and atrophic heel fat pad.
AB  - Light and electron microscopy was used for a histologic examination of normal
      heel fat pads and atrophic heel fat pads from patients with peripheral
      neuropathies. Histomorphometric analysis revealed an average 30% smaller mean
      cell area and 16% smaller mean cell diameters in the atrophic pads compared with
      the normal heel fat pads. Septal walls in the atrophic fat pads were often
      fragmented and approximately 75% wider than normal. Perineural fibrosis was also
      found in the atrophic heel fat pads. The Verhoeff elastic staining technique was
      used to determine the relative percentage of collagen to elastic tissue within
      the septae. No significant differences were noted between the normal and atrophic
      heels. The ultrastructure of the adipocytes from the normal and atrophic heel
      pads was similar to those found in abdominal subcutaneous fat. Lipid droplets of
      variable size and density thin the center of the adipocyte were surrounded by a
      thin border of cytoplasm. The interphase between adipocytes contained fine
      collagen and elastic fibers.

PMID- 7633581
TI  - A modified Chrisman-Snook procedure for reconstruction of the lateral ligaments
      of the ankle: review of 18 cases.
AB  - The outcome of 18 ankles of 16 patients who underwent a modification of the
      Chrisman-Snook lateral ligamentous reconstruction was analyzed. The modification
      described herein attempts a more anatomic reconstruction of the calcaneofibular
      ligament, while the anterior talofibular ligamentous reconstruction remains
      unchanged. All patients were evaluated before and after surgery by physical
      examinations and stress inversion radiographs were taken to measure the degree of
      talar tilt. Additional postoperative assessment consisted of a questionnaire,
      inversion and eversion isokinetic strength measurements, subtalar joint inversion
      stress radiographs (stress Broden's views), and a hop test to assess ankle
      confidence. An average preoperative talar tilt of 13.7 degrees was reduced to an
      average of 2.3 degrees after surgery. Post-operative subtalar stress radiographs
      revealed an average of 2.8 degrees of subtalar tilt compared with the "normal"
      average of 7.2 degrees in the nonoperative ankles. While no ankles were found
      before surgery to have a 3+ anterior drawer sign, 11 ankles had 3+ inversion
      laxity. Excessive inversion laxity, which can occur through both the ankle and
      subtalar joints, more than anterior drawer laxity, may appear to be the primary
      determinant of functional ankle instability in the chronic setting. We recommend
      subtalar stress radiographs, in addition to routine talar stress radiographs, to
      quantify the relative contributions of each of these joints to inversion laxity
      in a symptomatic patient to guide appropriate treatment. The described procedure
      will anatomically stabilize both joints to inversion stress.

PMID- 7633585
TI  - Symptomatic ossification of the tibiofibular syndesmosis in professional football
      players: a sequela of the syndesmotic ankle sprain.
AB  - Ankle syndesmosis sprains are common injuries in collegiate and professional
      football. Several reports have documented that patients with syndesmosis injuries
      require a longer time to return to full athletic participation than patients with
      lateral ankle sprains. Here we present the cases of two professional football
      players with ankle pain secondary to syndesmosis ossification following
      documented syndesmosis ankle sprains. Both patients eventually required resection
      of the heterotopic ossification to allow a pain-free return to football. We
      conclude that syndesmosis ossification may be symptomatic in some patients, and
      surgical excision of the ossification may be required to allow an asymptomatic
      return to sports.

PMID- 7633586
TI  - Bone scintigraphy in the assessment of the hallucal sesamoids.
AB  - Bone scintigraphy is frequently used to evaluate suspected hallucal sesamoid
      pathology. Increased scintigraphic activity of the hallucal sesamoid is assumed
      to corroborate clinical suspicion of pathology, but the incidence of such
      increased uptake has not been studied in an asymptomatic population. Using a 0 to
      2 bone scintigraphic rating system, 25 of 86 (29%) asymptomatic infantry recruits
      and 7 of 27 (26%) asymptomatic sedentary adults were found to have grade 1 or
      grade 2 activity. When using scintigraphy to evaluate hallucal sesamoid
      pathology, caution should be used in interpreting the meaning of increased
      scintigraphic activity.

PMID- 7633583
TI  - Measurement of the forefoot with roentgen stereophotogrammetry in hallux valgus
      surgery.
AB  - Eight hallux valgus patients were marked with tantalum markers in conjunction
      with hallux valgus surgery (seven proximal osteotomies and one chevron
      osteotomy). Changes on weightbearing before surgery as well as corrective changes
      after surgery were analyzed with roentgen stereophotogrammetry (RSA) and with
      standard x-rays. RSA is accurate to 0.6 degrees in rotational changes and 0.3 mm
      in translation. Weightbearing changes were inconsistent, and minimal with both
      standard x-rays and RSA. It was possible to analyze the correction at the
      osteotomy site with RSA. In half the cases, the correction measured by RSA
      corresponded with that measured with standard x-rays, within measurement error;
      in the other cases, RSA showed that the correction was of a different size or
      direction than that measured on standard x-rays. Corrective changes in hallux
      valgus surgery are complex, including angular and translational changes at
      several levels and in several joints in order to produce a clinical resultant.
      Rotational changes can be evaluated with RSA. Although RSA in an optimal
      situation is very accurate, it is still limited to a laboratory setting.

PMID- 7633584
TI  - First ray joint limitation, pressure, and ulceration of the first metatarsal head
      in diabetes mellitus.
AB  - Measurements of first ray mobility, pressure, and other variables were made on 19
      diabetic patients with a history of ulceration at the first metatarsal head, 20
      diabetic patients with a history of ulceration at other locations of the
      forefoot, 19 matched diabetic controls, and 19 matched nondiabetic controls.
      Patients with a history of first metatarsal head ulceration had significantly
      less first ray mobility and significantly higher pressure at the first metatarsal
      head compared with the other groups. Regression analysis found a moderate inverse
      linear relationship between first ray dorsiflexion and peak pressure at the first
      metatarsal head (R2 = 0.46, P < .0001). Results showed that sensory loss,
      duration of diabetes, and limited range of motion at the hip, ankle, and foot
      were related to ulcerations at all forefoot locations, Limited first ray mobility
      and high pressure at the first metatarsal head were related to ulcerations only
      at the first metatarsal head location.

PMID- 7633582
TI  - Measuring hallux valgus: a comparison of conventional radiography and clinical
      parameters with regard to measurement accuracy.
AB  - To assess the repeatability and error of conventional x-ray measurements, intra-
      and interobserver evaluations of measurement accuracy were done on 20
      preoperative and 40 postoperative (20 chevron and 20 proximal osteotomy) x-rays
      of hallux valgus patients. Standard x-rays showed an average interobserver error
      of measurement of 6.4 degrees for the hallux valgus angle, 5.4 degrees for the
      intermetatarsal angle, and 2.0 mm for the intermetatarsal distance. The
      intraobserver error did not differ greatly. The repeatability and error of two
      clinical measurements, ball circumference, and dorsal to plantar range of motion
      of the first metatarsophalangeal joint were evaluated for 20 healthy volunteers.
      The ball circumference had an average measurement error of 1.1 cm, whereas the
      dorsal and plantar range of motion of the great toe had an average measurement
      error of 12 degrees in dorsiflexion and 16 degrees in plantarflexion. In both
      clinical and radiographic parameters, linear measurements were more accurate than
      angular measurements. Although x-rays are of value in hallux valgus surgery,
      standard x-rays are less accurate than previously assumed. Small changes produced
      by osteotomies may be hidden by the postoperative measurement error. The results
      of hallux valgus surgery should primarily be evaluated clinically. When clinical
      and radiological evaluations are made, linear measurements may be preferable.

PMID- 7633587
TI  - Calcific bursitis in a three-year-old boy: a case report.
AB  - This is a case report of calcific bursitis adjacent to the first
      metatarsophalangeal (MP) joint in a 3-year-old boy. The patient had two attacks
      of pain on the medial side of the first MP joint, resembling an acute gouty
      attack. Roentgenograms showed calcified opacity adjacent to the medial side of
      the first MP joint. Surgical removal of the calcified bursa was performed. X-ray
      analyses revealed that this calcified deposit was hydroxyapatite.

PMID- 7633588
TI  - Plantar medial subluxation of the medial cuneiform: case report of an uncommon
      variant of the Lisfranc injury.
AB  - An uncommon injury of plantar medial subluxation of the medial cuneiform as a
      variant of the Lisfranc fracture subluxation is presented. The mechanism of
      injury is discussed and a comparison is made to previous case reports of variants
      of medial cuneiform injury.

PMID- 7633589
TI  - The ball-and-socket ankle: a case history and literature review.
AB  - The ball-and-socket ankle is a rare clinical condition that has a deformity of
      the talotibial articulation. Assorted anomalies frequently exist. Treatment is
      usually based on clinical presentation of a foot problem.

PMID- 7633590
TI  - Second metatarsophalangeal joint instability.

PMID- 7633591
TI  - Deltoid ligament forces after tibialis posterior tendon rupture: effects of
      triple arthrodesis and calcaneal displacement osteotomies.

PMID- 7633592
TI  - Preparative chromatographic separations in pharmaceutical, diagnostic, and
      biotechnology industries: current and future trends.
AB  - Chromatography is widely employed in industry for the purification of
      biotherapeutics and diagnostics. Regulatory requirements dictate that the
      chromatographic process be reproducible and provide the necessary product purity.
      Current trends in designing and implementing purification strategies take into
      consideration the requirements for both chromatography media and equipment.
      Future trends will require that cost containment is considered. New
      chromatography materials, new methods for equipment design analysis, and new
      technologies to ensure regulatory compliance will provide the biotechnology
      industry with tools to provide tomorrow's products.

PMID- 7633593
TI  - Current trends in molecular recognition and bioseparation.
AB  - Molecular recognition guides the selective interaction of macromolecules with
      each other in essentially all biological processes. Perhaps the most impactful
      use of biomolecular recognition in separation science has been in affinity
      chromatography. The results of the last 26 years, since Cuatrecases, Wilchek and
      Anfinsen first reported the purification of staphylococcal nuclease, have
      validated the power of biomolecular specificity for purification. This power has
      stimulated an explosion of solid-phase ligand designs and affinity
      chromatographic applications. An ongoing case in point is the purification of
      recombinant proteins, which has been aided by engineering the proteins to contain
      Affinity-Tag sequences, such as hexa-histidine for metal-chelate separation and
      epitope sequence for separation by an immobilized monoclonal antibody. Tag
      technology can be adapted for plate assays and other solid-phase techniques. The
      advance of affinity chromatography also has stimulated immobilized ligand-based
      methods to characterize macromolecular recognition, including both
      chromatographic and optical biosensor methods. And, new methods such as phage
      display and other diversity library approaches continue to emerge to identify new
      recognition molecules of potential use as affinity ligands. Overall, it is
      tantalizing to envision a continued evolution of new affinity technologies which
      use the selectivity built into biomolecular recognition as a vehicle for
      purification, analysis, screening and other applications in separation sciences.

PMID- 7633594
TI  - Peptide chiral purity determination: hydrolysis in deuterated acid,
      derivatization with Marfey's reagent and analysis using high-performance liquid
      chromatography-electrospray ionization-mass spectrometry.
AB  - A high-performance liquid chromatography-electrospray ionization-mass
      spectrometric (LC-ESI-MS) method is presented that allows rapid and accurate
      determination of amino acid chiral purity in a peptide. Peptides are hydrolyzed
      in hydrochloric acid-d1/acetic acid-d4 and then converted to diastereomers by
      derivatization with 1-fluoro-2,4-dinitrophenyl-5-L-alanine amide (FDAA, Marfey's
      reagent). Mixtures of D- and L-amino acid diastereomeric pairs are resolved in
      one chromatographic separation using conventional reversed-phase high-performance
      liquid chromatography. Hydrolysis in a deuterated solvent is necessary because
      the original ratio of D-/L-amino acids present in a peptide changes during acid
      hydrolysis due to racemization. Peptide hydrolysis in deuterated acids
      circumvents this problem by labeling each amino acid that racemizes with one
      deuterium at the alpha-carbon. An increase in molecular mass of one atomic mass
      unit allows racemized amino acids to be distinguished from non-racemized amino
      acids by mass spectrometry. This procedure was used to determine the chiral
      purity of each amino acid in a purified, hexapeptide by-product (Arg-Lys-Lys-Asp
      Val-Tyr) present in a kilogram batch of the synthetic pentapeptide, thymopentin
      (Arg-Lys-Asp-Val-Tyr).

PMID- 7633596
TI  - Purification and characterization of insulin-like growth factor II (IGF II) and
      an IGF II variant from human placenta.
AB  - In order to purify variant IGF II peptides from human placenta, we have developed
      a purification procedure combining heparin affinity chromatography and cation
      exchange, reversed-phase and size-exclusion HPLC. Two peptides were purified,
      both having apparent M(r) values of ca. 7300 Da as evaluated by SDS-PAGE. N
      Terminal sequencing revealed IGF II and an IGF II variant in which Ser29 was
      replaced by the tetrapeptide Arg-Leu-Pro-Gly. The final yield of variant IGF II
      was about eight-fold lower than that of IGF II. Both pure peptides were
      functionally active as they bound to type I and type II IGF receptors from ovine
      and human placental membranes, as determined by crosslinking experiments and
      displacement curve studies.

PMID- 7633595
TI  - High-performance liquid chromatography-thermospray mass spectrometry of omega
      carboxyleukotriene B4 and omega-hydroxyleukotriene B4 from an incubation mixture
      of human colonic well-differentiated adenocarcinoma homogenate.
AB  - A method for the analysis of omega-carboxyleukotriene B4 and omega
      hydroxyleukotriene B4 in human colonic carcinoma homogenate is described. The
      hydroxy groups of the leukotriene metabolite were acetylated by acetic anhydride,
      and the mixture was partially purified on a Sep-Pak C18 cartridge and analysed by
      reversed-phase HPLC-thermospray MS. Generally, the base ion, [MH-2(60)]+, is
      produced through elimination of two acetic acid (60 mass units) molecules from
      the protonated molecular ion. On selected-ion monitoring, standard curves for
      omega-carboxy- or omega-hydroxyleukotriene B4 showed a linear relationship over
      the range 72-1500 pmol. The assay based on selected-ion monitoring was applied to
      an extract from human colonic carcinoma homogenate. When a homogenate of human
      colonic well-differentiated adenocarcinoma was incubated with NADPH and
      leukotriene B4 (60.6 nmol) as a substrate, the conversion of precursor
      leukotriene B4 to omega-carboxyleukotriene B4 or omega-hydroxyleukotriene B4 was
      0.33 or 3.17%, respectively. Based on these results, it is suggested that
      carcinoma cells themselves or leukocytes at the hostsite in a region of human
      colonic well-differentiated adenocarcinoma are performing omega-oxidation through
      NADPH-dependent omega-hydroxylation of leukotriene B4.

PMID- 7633597
TI  - DNA-immobilized polyhydroxyethylmethacrylate microbeads for affinity sorption of
      human immunoglobulin G and anti-DNA antibodies.
AB  - Polyhydroxymethacrylate (PHEMA) microbeads were prepared by a suspension
      polymerization technique and activated by CNBr in an alkaline medium (pH 11.5).
      DNA molecules were immobilized onto CNBr-activated PHEMA beads. The amount of
      immobilized DNA was controlled by changing the medium pH and the initial
      concentrations of CNBr and DNA. The maximum DNA immobilization was observed at pH
      5.0. Non-specific adsorption on the plain PHEMA microbeads was less than 0.1
      mg/g. Much higher values, up to 2.75 mg/g, were achieved with the CNBr-activated
      PHEMA microbeads. Human immunoglobulin G (HIgG) adsorption onto PHEMA microbeads
      containing different amounts of DNA on their surfaces from aqueous solutions
      containing different amounts of HIgG at different pH values was investigated. The
      maximum HIgG adsorption was observed at pH 7.0. Non-specific HIgG adsorption onto
      the plain PHEMA microbeads was low (about 0.167 mg/g). Higher adsorption values,
      up to 7.5 mg/g, were obtained with the DNA-PHEMA beads. HIgG and anti-DNA
      antibody removal from the blood plasma obtained from a healthy donor and a
      patient with systemic lupus erythematosus (SLE) were also investigated. The
      maximum amounts of HIgG adsorbed from aqueous solution and human plasma onto the
      DNA-PHEMA microbeads were 7.35 and 23.46 mg/g, respectively. Anti-DNA antibody
      adsorption value was 40 mg/g.

PMID- 7633598
TI  - Assay of neopterin in serum by means of two-dimensional high-performance liquid
      chromatography with automated column switching using three retention mechanisms.
AB  - An automated two-dimensional HPLC method for the determination of neopterin in
      serum is described. Neopterin is separated from proteins on a short
      octadecylsilica column by size exclusion and from the majority of the other serum
      components by adsorption. The fraction containing neopterin is transferred by
      column switching to a solvent-generated cation-exchange column using
      dodecylsulfonic acid as surface activator. Parameters influencing the separation
      performance and sensitivity of the fluorescence detection are discussed. The
      efficiency of the cleaning of the first column was optimized. The method was
      validated. It achieves a precision of 1% (R.S.D.) and a detection limit of about
      0.3 nmol/l. The accuracy is nearly 100%. The method allows a high sample
      throughput, requiring 15 min per sample.

PMID- 7633599
TI  - Selective separation of human peripheral platelets, granulocytes and lymphocytes
      by surface affinity chromatography.
AB  - Selective separation of human peripheral platelets, granulocytes and lymphocytes
      was investigated by column liquid chromatography using methoxyethoxymethyl (MEM)
      bonded-phase columns (25 x 0.9 cm I.D.). Isotonic solutions containing mono- and
      disaccharides, methyl-alpha-D-pyranosides and a physiological saline at pH 7.4
      were used as the mobile phase. Granulocytes and lymphocytes were separated on the
      MEM-Cellulofine GH-25 column by elution with 0.3 M D-mannose solution. The
      isolation of platelets and lymphocytes from human leukocyte-rich plasma was
      performed with a MEM-Sephadex G25 column and elution with 0.27 M sucrose
      solution. On the same column platelets could also be collected selectively by
      elution with 0.31 M methyl-alpha-D-mannoside at the high recovery of 100%. The
      isolated cells were viable for more than 90%.

PMID- 7633600
TI  - Determination of d-amphetamine in biological samples using high-performance
      liquid chromatography after precolumn derivatization with o-phthaldialdehyde and
      3-mercaptopropionic acid.
AB  - An HPLC method is described for the determination of amphetamine using
      fluorometric detection after derivatization with o-phthaldialdehyde and 3
      mercaptopropionic acid. This procedure is more sensitive (detection limit 370
      fmol in microdialysate buffer standards, 1.5 pmol in extracted plasma and tissue
      samples) than most of the previous methods described for the determination of
      amphetamine with HPLC-fluorescence detection. Due to the stability of the
      derivative it is also suitable for autosampling after manual derivatization.
      Investigators currently using o-phthaldialdehyde derivatization and fluorometric
      detection for amino acid determination should be able to rapidly implement this
      method.

PMID- 7633602
TI  - Determination of felodipine, its enantiomers, and a pyridine metabolite in human
      plasma by capillary gas chromatography with mass spectrometric detection.
AB  - Sensitive methods based on capillary gas chromatography (GC) with mass
      spectrometric (MS) detection in a selected-ion monitoring mode (SIM) for the
      determination of racemic felodipine, its enantiomers, and a pyridine metabolite
      in human plasma are described. Following liquid-liquid extraction from plasma,
      enantiomers of felodipine were separated on a chiral HPLC column (Chiralcel OJ)
      and fractions containing each isomer were collected on a continuous basis using a
      fraction collector. These fractions were later analyzed by GC-MS-SIM. A similar
      method based on GC-MS-SIM detection was developed for the determination of
      racemic felodipine and its pyridine metabolite with a minor modification of
      sample preparation. The limits of quantitation in plasma were 0.1 ng/ml for both
      the R(+)- and S(-)-enantiomers of felodipine and 0.5 ng/ml for both racemic
      felodipine and its pyridine metabolite. The stereoselective assay was used to
      support a clinical study with racemic felodipine, and was capable of analyzing
      more than 30 plasma samples per day.

PMID- 7633601
TI  - Direct injection for high sample throughput capillary gas chromatographic-mass
      spectrometric bioanalysis.
AB  - Because of the drawback of the relatively long analysis times inherent to
      temperature-programmed splitless injection capillary GC-MS, isothermal direct
      injection capillary GC-MS was investigated for quantitative bioanalysis. Using
      extracts from spiked plasma samples, we showed that high quality chromatography
      with a run time much shorter than that achievable with splitless injection can be
      achieved with direct injection. Sensitivity and other performance parameters were
      as good as or better than those of the splitless method. Since sample throughput
      is of great importance in laboratories that analyze thousands of biological
      samples, it is recommended that, when possible, splitless injection, which has
      traditionally been used in trace level GC-MS bioanalytical methods, be replaced
      by direct injection.

PMID- 7633604
TI  - Comparison of the carbohydrate biological response modifiers Krestin,
      schizophyllan and glucan phosphate by aqueous size exclusion chromatography with
      in-line argon-ion multi-angle laser light scattering photometry and differential
      viscometry detectors.
AB  - A major barrier to the development, preclinical and clinical application of
      natural carbohydrate biological response modifiers has been the difficulty
      involved in accurately characterizing carbohydrate polymers with molecular masses
      ranging from 10(4) to 10(7) g/mol. Herein, we employed size exclusion
      chromatography with multi-angle laser light scattering and differential
      viscometry to compare and contrast structural properties of the biological
      response modifiers Krestin, schizophyllan and glucan phosphate. Krestin,
      schizophyllan and glucan phosphate exhibit significant differences in molecular
      mass moments, molecular mass distribution, polymer sizes, intrinsic viscosity and
      perhaps their solution behaviour. This knowledge of precise physicochemical data
      is required for a better understanding of the properties and higher structure of
      complex carbohydrate biological response modifiers.

PMID- 7633603
TI  - Determination of valproic acid and its metabolites using gas chromatography with
      mass-selective detection: application to serum and urine samples from sheep.
AB  - An improved method for the quantitative determination of valproic acid (VPA) and
      sixteen of its metabolites has been developed using gas chromatography-mass
      spectrometry with selected-ion monitoring. The method is applicable to serum or
      urine and all metabolites are measured in a single chromatographic run of 29.5
      min. Ions selected for quantitative purposes were the characteristic [M-57]+ ions
      of the tert.-butyldimethylsilyl (tBDMS) derivatives. The method utilizes
      heptadeuterated VPA as well as six heptadeuterated metabolites as internal
      standards [i.e. 2-[2H7]propyl-2-pentenoic acid (2-ene[2H7]VPA), 2-[2H7]propyl-4
      pentenoic acid (4-ene[2H7]VPA), 2-[2H7]propyl-3-oxopentanoic acid (3
      keto[2H7]VPA), 2-[2H7]propyl-4-oxopentanoic acid (4-keto[2H7]VPA), 2-[2H7]propyl
      3-hydroxypentanoic acid (3-OH[2H7]VPA), 2-[2H7]propyl-5-hydroxypentanoic acid (5
      OH[2H7]VPA)]. The method demonstrates very good accuracy and precision over a
      large range of concentrations for VPA and all metabolites measured in both human
      and sheep biological fluids. The assay was applied to the analysis of VPA and
      metabolites in serum and urine samples collected from three non-pregnant ewes
      following intravenous bolus administration of a mixture of VPA and [13C4]VPA.
      Sheep were observed to produce measurable quantities of the majority of
      metabolites found in humans, with the notable exception of the di-unsaturated
      compounds (i.e. 2,3'-diene VPA and 2,4-diene VPA). The pharmacokinetics and
      metabolism of VPA and [13C4]VPA appear to be equivalent in the sheep model. The
      elimination half-life of VPA and [13C4]VPA in the ewe were estimated to be
      approximately 3.5 +/- 0.4 and 3.2 +/- 0.4 h, respectively.

PMID- 7633605
TI  - Enantioselective determination of pazinaclone, a new isoindoline anxiolytic, and
      its active metabolite in rat plasma by high-performance liquid chromatography.
AB  - A sensitive and specific high-performance liquid chromatographic method has been
      developed for the simultaneous determination of the enantiomers of pazinaclone
      (DN-2327), a new anxiolytic agent, and those of its active metabolite, M-II, in
      rat plasma. Organic solvent extraction of pazinaclone, M-II, and internal
      standard (I.S.) in plasma was followed by separation of the analytes from other
      metabolites using an achiral reversed-phase column. Fluorescence detection was
      employed with excitation and emission wavelengths of 328 and 367 nm,
      respectively. Separation of all the enantiomers and I.S. was then accomplished
      with normal- and chiral-phase columns connected in series. For each analyte, the
      lower quantitation limit was 0.5 ng/ml. The assay has been applied to a chiral
      inversion study in rats. Chiral conversion from one enantiomer of pazinaclone to
      the other hardly occurred. This method is suitable for enantioselective
      pharmacokinetic and toxicokinetic studies in animals.

PMID- 7633607
TI  - High-performance liquid chromatographic method for the determination of AG-331, a
      novel anti-cancer agent, in human serum and urine using solid-phase extraction
      and photodiode-array detection.
AB  - A reversed-phase isocratic high-performance liquid chromatographic method has
      been developed for the determination of AG-331, a novel thymidylate synthase
      inhibitor, in human serum and urine. The method involves a solid-phase extraction
      from C18 cartridges without addition of an internal standard. The methanol eluent
      is evaporated under nitrogen at 40 degrees C, and reconstituted in mobile phase,
      acetonitrile-water (35:65, v/v) containing 25 mM ammonium phosphate. Separation
      of AG-331 was obtained on a C18 column at a flow-rate of 1 ml/min.
      Chromatographic signals were monitored by a photodiode-array detector at a
      primary wavelength of 457 nm with a bandwidth of 4.8 nm. Standard curves are
      linear in the range of 22-2175 ng/ml in plasma and 44-2175 ng/ml in urine,
      respectively. The extraction recovery ranged from 92.9-102.4%. Intra-day
      coefficient of variation was less than 9.5%, and inter-day coefficient of
      variation was less than 14.3% for an AG-331 concentration of 44 ng/ml. This
      method has been used to characterize the pharmacokinetics of AG-331 in cancer
      patients as part of ongoing Phase I trials.

PMID- 7633606
TI  - Determination of anticancer drug vitamin K3 in plasma by high-performance liquid
      chromatography.
AB  - Synthetic vitamin K3 (VK3, 2-methyl-1,4-naphthoquinone, or menadione) has been
      found to exhibit antitumor activity against various human cancer cells at
      relative high dose. Parallel to our study on the mechanism of VK3 action and for
      future clinical trials in Taiwan, we developed a simple, sensitive and accurate
      high-performance liquid chromatographic method for the determination of VK3 in
      biological fluids. VK3 was extracted from the plasma samples with n-hexane. The
      chromatographic separation employed an ODS analytical column (5 microns, 250 x
      4.6 mm I.D.) with a mobile phase of methanol-water (70:30, v/v) and UV detection
      at 265 nm. On completely drying of the extraction solution, n-hexane, by a stream
      of nitrogen, menadione was lost to a great extent. Methanol (70%, 200
      microliters) was added to the extraction solvent after extraction and
      centrifugation to prevent the loss of menadione. The absolute recovery was 82.4
      +/- 7.69% (n = 7). The within-day and between-day calibration curves of VK3 in
      plasma in the ranges of interest (0.01-10.00 micrograms/ml; 0.01-5.00
      micrograms/ml) showed good linearity (r > 0.999) and acceptable precision. The
      limit of quantitation of VK3 was 10 ng/ml in plasma. This method has been
      successfully applied to a pilot pharmacokinetic study of VK3 in rabbits receiving
      an intravenous high-dose bolus injection of 75 mg menadiol sodium diphosphate
      (Synkayvite). The pharmacokinetic properties of menadione could be described
      adequately by an open two-compartment model. The mean half-life of menadiol
      (transformation to menadione) was 2.60 +/- 0.12 min.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7633608
TI  - Evaluation and routine application of the novel restricted-access precolumn
      packing material Alkyl-Diol Silica: coupled-column high-performance liquid
      chromatographic analysis of the photoreactive drug 8-methoxypsoralen in plasma.
AB  - A fully automated coupled-column HPLC method for on-line sample processing and
      determination of the photoreactive drug 8-methoxypsoralen (8-MOP) in plasma has
      been developed. The method is based on the novel internal-surface reversed-phase
      precolumn packing materials Alkyl-Diol Silica (ADS). This new family of
      restricted-access materials has a hydrophilic, electroneutral outer particle
      surface and a hydrophobic internal pore surface. The supports tolerate the direct
      and repetitive injection of proteinaceous fluids such as plasma and allow a
      classical C18-, C8- or C4-reversed-phase partitioning at the internal (pore)
      surface. The total protein load, i.e. the lifetime of the precolumn used in this
      study (C8-Alkyl-Diol Silica, 25 microns, 25 x 4 mm I.D.), exceeds more than 100
      ml of plasma. 8-MOP was detected by its native fluorescence (excitation 312 nm,
      emission 540 nm). Validation of the method revealed a quantitative and matrix
      independent recovery (99.5-101.3% measured at five concentrations between 21.3
      and 625.2 ng of 8-MOP per milliliter of plasma), linearity over a wide range of 8
      MOP concentrations (1.2-3070 ng of 8-MOP/ml, r = 0.999), low limits of detection
      (0.39 ng of 8-MOP/ml) and quantitation (0.79 ng of 8-MOP/ml) and a high between
      run (C.V. 1.47%, n = 10) and within-run (C.V. 1.33%, n = 10) reproducibility.
      This paper introduces coupled-column HPLC as a suitable method for on-site
      analysis of drug plasma profiles (bedside-monitoring).

PMID- 7633609
TI  - Enantioselective high-performance liquid chromatographic determination of
      omeprazole in human plasma.
AB  - A new stereoselective HPLC assay was developed to isolate omeprazole enantiomers
      from human plasma using C2 solid-phase extraction cartridges and an analogue was
      used as internal standard. Recoveries of the (+)-isomer were 83.4 and 89.7% at
      100 and 250 ng/ml, respectively. Recoveries of the (-)-isomer were 78.4 and
      82.8%, respectively. Recovery of the internal standard averaged 77.2%. Direct
      chiral separation of the enantiomers is achieved on a Resolvosil BSA-7 chiral
      column (15 cm x 4 mm I.D.) and a matching guard column. The mobile phase is a
      variable amount of n-propanol (0.05-1.0%) in 0.05 M ammonium phosphate buffer (pH
      7.0) and the flow-rate is 1.5 ml/min. Drug absorbance is monitored at 302 nm.
      Standard curves are linear from 15 to 250 ng/ml for each enantiomer. The
      coefficients of variation for intra-day precision at each concentration over the
      range of the standard curve were between 0.98 and 10.87%. The coefficients of
      variation for inter-day precision for the analyses of omeprazole enantiomers in
      plasma (30 and 175 ng/ml) were less than 10% over a four month interval.

PMID- 7633610
TI  - Rapid high-performance liquid chromatographic method for the quantitation of
      polyamines as their dansyl derivatives: application to plant and animal tissues.
AB  - A rapid high-performance liquid chromatographic method for the separation of
      polyamines as their dansyl derivative has been developed. The chromatographic
      system used consisted of a reversed-phase column and a mobile phase of
      acetonitrile and water. The separation of 1,3-diaminopropane, putrescine,
      cadaverine, spermidine and spermine takes only 9 min. This method provides a good
      resolution between 1,3-diaminopropane and putrescine. It has been applied to
      quantify polyamines from seeds of wheat, petals of Phalaenopsis hybrids and
      various rat tissues.

PMID- 7633611
TI  - High-performance liquid chromatographic analysis of beta-phenylethylamine for the
      estimation of in vivo protein synthesis.
AB  - A rapid, sensitive, and automated reversed-phase liquid chromatographic method
      was developed for the analysis of phenylalanine as beta-phenylethylamine, for the
      measurement of in vivo protein synthesis. beta-Phenylethylamine was derivatized
      with o-phthaldialdehyde (OPA) to form a fluorescent derivative that was
      successfully measured in tissue cell fluids and hydrolysates as the
      decarboxylation product of phenylalanine. The system was extremely sensitive
      enabling the accurate determination of 0.5 pmol in biological samples. Analysis
      time was less than 11 min, so that 130 samples can be analysed per day. The
      method eliminates the need for time-consuming column extraction procedures. This
      method offers substantial advantages over existing methods for the isolation and
      determination of beta-phenylethylamine.

PMID- 7633612
TI  - Determination of serum retinol by reversed-phase high-performance liquid
      chromatography.
AB  - A rapid, sensitive and specific high-performance liquid chromatographic method
      was developed for the determination of serum levels of retinol in humans. A
      direct serum injection technique after deproteinisation was used to avoid lengthy
      pretreatment steps which can result in degradation of retinol during analysis.
      The column used was CLC-ODS, the mobile phase was acetonitrile-water and
      detection wavelength was 328 nm. Deterioration in column performance was not
      observed even after injection of 300 samples. The lower detection limit was 10
      micrograms/l. On analyzing a serum pool six times, a C.V. of 0.7% was obtained.
      The method is quantitative, reproducible, rapid and highly accurate for routine
      analysis.

PMID- 7633613
TI  - Simple and specific reversed-phase liquid chromatographic method with diode-array
      detection for simultaneous determination of serum hydroxychloroquine, chloroquine
      and some corticosteroids.
AB  - This paper describes a simple, specific, and sensitive high-performance liquid
      chromatographic (HPLC) method using ion-pair reversed-phase chromatography with
      photodiode-array detection for the simultaneous determination of
      hydroxychloroquine (HCQ) and chloroquine (CQ) in serum samples from rheumatoid
      arthritis patients receiving either HCQ sulphate or CQ diphosphate. The assay is
      also applicable to the simultaneous determination of corticosteroids. The method
      consisted of two diethyl ether extractions of 1.0 ml of serum, to which two
      internal standards (2,3-diaminonaphthalene and 18-hydroxy-11-deoxycorticosterone)
      and 1.0 ml of 0.25 M sodium hydroxide had been added. After the organic phase was
      evaporated to dryness at 30-40 degrees C under a stream of nitrogen, the extract
      was reconstituted with a 1:1 mixture of 0.1 M perchloric acid and methanol, an
      aliquot of which was injected on to the system. Peak-height ratios at different
      wavelengths (A245/343, A245/256, A245/265 and A245/275) were utilized as a method
      of assessing peak homogeneity. Some anti-inflammatory drugs which may be used for
      rheumatic disorders were shown not to interfere with the assay. The method
      provides selectivity by using diode-array detection at several wavelengths. The
      use of two internal standards not only compensates for losses during the sample
      manipulation but also prevents erroneous results in case of interference.

PMID- 7633617
TI  - Outpatient instruction for individuals with COPD.
AB  - Educating individuals with COPD is an important part of their overall medical and
      nursing management. Due to the debilitating nature of the disease, care must be
      exercised to offer programs that meet the participants' individual needs. Classes
      should be offered at a convenient time and place. To facilitate discussion, class
      size should be kept small. Family members and significant others should be
      encouraged to attend the classes to reinforce what is taught in class and to
      provide support and encouragement. Finally, measuring outcomes is important in
      order to demonstrate the overall effectiveness of the program; however,
      instruments used to measure effectiveness must be simple, easy to administer, and
      complete. Helping individuals manage their COPD presents a real challenge to
      nurses. A well-designed educational program is one cost-effective measure that
      can meet this challenge.

PMID- 7633616
TI  - Determination of a novel xanthine derivative, MKS 213-492, in plasma by high
      performance liquid chromatography with electrochemical detection.
AB  - A reversed-phase liquid chromatographic method with coulometric detection has
      been developed for the determination of free MKS 213-492 (a novel xanthine
      derivative) in plasma. This method is based on a simple and rapid plasma
      extraction procedure using precolumn-switching. The oxidation of this
      pharmacologically active xanthine derivative was optimized with respect to
      applied potential, pH of mobile and rinsing phase and rinsing time. The detection
      limit for MKS 213-492 was found to be 54 pg/injection.

PMID- 7633615
TI  - Determination of quinapril and quinaprilat by high-performance liquid
      chromatography with radiochemical detection, coupled to liquid scintillation
      counting spectrometry.
AB  - Quinapril and quinaprilat concentrations were determined in perfusate, urine, and
      perfusate ultrafiltrate using a specific and sensitive reversed-phase high
      performance liquid chromatographic procedure with radiochemical detection,
      coupled to liquid scintillation counting spectrometry. Quinapril and quinaprilat
      were measured in perfusate and urine after pretreatment with acetonitrile and
      subsequent centrifugation. Perfusate ultrafiltrate was used as collected. Two
      quinapril diketopiperazine metabolites, PD 109488 and PD 113413, were separated
      chromatographically from quinapril, quinaprilat, and from each other. Assay
      performance for quinapril and quinaprilat was assessed by examining precision and
      accuracy of the assay over four days. Using a 100-microliters sample volume, the
      limit of quantitation for both 3H-quinapril and 3H-quinaprilat (sp. act.
      approximately 2.0 muCi/micrograms) was 1 ng/ml.

PMID- 7633614
TI  - Determination of fumagillin in muscle tissue of rainbow trout using automated ion
      pairing liquid chromatography.
AB  - A high-performance liquid chromatographic assay is described as a routine
      analytical method for the determination of fumagillin in rainbow trout muscle
      tissue. Muscle tissue samples (1 g) containing fumagillin were deproteinized with
      8 ml of an acetonitrile-water mixture (2:6, v/v). The extracts were purified with
      a Bond Elut Octyl C8 cartridge column, washed with a water-methanol mixture
      (95:5, v/v; 4 ml) and fumagillin was eluted with acetonitrile (1 ml). Analytical
      separations were performed by reversed-phase HPLC with UV detection at 351 nm
      under gradient conditions. The mobile phase was acetonitrile-0.005 M tetrabutyl
      ammonium phosphate in water (pH 7.8). The assay is specific and reproducible
      within the fumagillin range of 20-1000 ng/g and recovery at 20 ng/g was 69.2%.
      Sample preparation involves the use of a robotic sample preparation system.
      Gravimetric validation of all operations enabled Good Laboratory Practices to be
      observed.

PMID- 7633620
TI  - An examination of patients' experiences with mechanical ventilation.

PMID- 7633618
TI  - Karen Mitchell, BSN RN.

PMID- 7633619
TI  - RNS president's message: 'simple does' is not 'as simple is'.

PMID- 7633622
TI  - [Miotics and occlusion in the treatment of accommodative strabismus].
AB  - Antisuppressive occlusion is an intermittent occlusion prescribed in order to
      eliminate suppression. This way, the system of vergences is reactivated which
      results in a stabilisation of the position of the eyes and reduces asthenopic
      complaints. Miotics are used to treat a recent or intermittent convergent squint.
      Miotics can equally be used to remove positive glasses and to reduce a visible
      postoperative recurrence.

PMID- 7633623
TI  - [Surgical treatment of accommodative esotropia].
AB  - Since Donders 1862 the treatment of accommodative esotropia is optical: without
      an hypermetropic correction, the accommodation needed for vision at distance
      induces a convergence and an accommodative convergence excess at near. But since
      130 years, new clinical and physiological research enables us to propose in
      specific cases a surgical treatment as an alternative to optical treatment. One
      of the clinical arguments is the low incidence of strabismus in hypermetropic
      patients: they can see clear at near and at distance without squinting. One of
      the physiological arguments is the research by J. Semmlow concerning the near
      triad: his model demonstrates that the system of accommodation and vergence are
      interconnected: the accommodative system participates to vergence but also the
      vergence system participates to accommodation, this is less known. The
      indications, the technique and surgical treatment are exposed. The analysis of
      the results by G. Gauthier and J.L. Vercher of the "Laboratoire de Controles
      Sensorimoteurs" at Marseille of the measures of the AC/A ratio confirms the model
      of Semmlow. The vertical syndrome observed in the accommodative squint is
      supposed to be the most frequent cause of putting the loop of the vergence system
      open.

PMID- 7633621
TI  - Clinical exemplars: sharing profiles of excellence in practice.

PMID- 7633624
TI  - [Surgical complications in accommodative esotropia].
AB  - The most important causes of surgical failure of accommodative strabismus are
      discussed and treatment is proposed. Limitations of duction are the most frequent
      causes and are to be carefully searched for. Postoperative diplopia is most often
      transitory and will be treated if it causes an obstacle to fusion. The prevention
      of surgical complications results in the long experience in motility examination
      and the system of combined horizontal and cyclovertical surgery.

PMID- 7633625
TI  - [Development of the AC/A ratio following surgery of accommodative esotropia].
AB  - Whether surgery should be used to correct for accommodative esotropia is still
      largely debated among strabologists. Fincham's theory (Fincham and Walton, 1957),
      describing the interaction between accommodation and vergence control systems
      (accommodative vergence and vergence accommodation), has been extensively
      studied. Models suggest that weakening of the accommodative vergence should
      correct esotropia. To test the model proposed by Semmlow (1981), we compared AC/A
      ratios in esotropic children and age-related normals (orthophoric) and monitored
      AC/A ratios for immediate (first week) and long term (1-2 months) changes in
      esotropic children following surgical correction. The AC/A ratio was determined
      at near and far. The accommodation stimulus was modified using lenses. The slope
      of the regression line between accommodation stimulus and disparity provided a
      measurement of AC/A ratio. Preliminary results show a normalisation of AC/A ratio
      occurring during the first month after surgery, supporting Semmlow's model and
      validating surgery as a means to correct for accommodative esotropia.

PMID- 7633626
TI  - [History of accommodative strabismus].
AB  - Starting with the ideas of Donders, a method has been developed of non-surgical
      treatment of the so-called accommodative esotropia (glasses, bifocals, prisms,
      miotics), surgery being only considered if insufficient results are obtained:
      these results are analyzed. The method of Gobin is in opposition with this method
      by not admitting the role of hypermetropia and by doing systematically a "four
      muscles surgery" (on two medial recti and on two oblique muscles).

PMID- 7633627
TI  - The interactive processes of accommodation and vergence.
AB  - A near target generates two different, though related stimuli: image disparity
      and image blur. Fixation of that near target evokes three motor responses: the so
      called oculomotor "near triad". It has long been known that both disparity and
      blur stimuli are each capable of independently generating all three responses,
      and a recent theory of near triad control (the Dual Interactive Theory) describes
      how these stimulus components normally work together in the aid of near vision.
      However, this theory also indicates that when the system becomes unbalanced, as
      in high AC/A ratios of some accommodative esotropes, the two components will
      become antagonistic. In this situation, the interaction between the blur and
      disparity driven components exaggerates the imbalance created in the vergence
      motor output. Conversely, there is enhanced restoration when the AC/A ratio is
      effectively reduced surgically.

PMID- 7633628
TI  - [Donders' school--conservative treatment].
AB  - Physiopathological and clinical characteristics of accommodative strabismus are
      described. Medical treatment consists in correcting full cycloplegic refractive
      error. Bifocal lenses are useful in accommodative non refractive esotropia.
      Surgery aims to correct the residual esotropia with full optical correction.

PMID- 7633629
TI  - [Arguments against surgical correction of pure accommodative strabismus].
AB  - Studies have shown recently that the occurrence of a pure accommodative
      strabismus has to be treated immediately with a full optical correction to
      preserve the stereoscopy. The use of little prisms can be very useful to complete
      the medical treatment. The dysfunction of the oblique muscles is not frequent and
      often without clinical signification. The interest of a surgical overcorrection,
      specially if it is cyclo-horizontal, to suppress the spectacle is not proven.

PMID- 7633630
TI  - Emmetropisation and accommodation in hypermetropic children before they show
      signs of squint--a preliminary analysis.
AB  - 1119 hypermetropic children have been followed from the age of 6 months to 3 1/2
      years. Observations are reported on (i) the changes in their refraction and (ii)
      their accommodation. Children who eventually had either a convergent squint or a
      microtropia were significantly (i) less likely to have spontaneously reduced
      their hypermetropia, and (ii) more likely to have problems with their
      accommodation, than those who had no squint. These abnormalities were
      demonstrated in both the fixing and the non-fixing eyes. There was no obvious
      difference between the findings for children who had microtropia and squint. We
      suggest that there was a basic defect in the function, and/or the development, of
      the visual systems relating to both fixing and non-fixing eyes of children who
      had squint or microtropia; and that this defect was present before squint or
      microtropia were diagnosed. The question of whether this defect had a congenital
      or an acquired (form vision deprivation) cause is discussed.

PMID- 7633631
TI  - [Psychological impact of eyeglasses].
AB  - Children with a strabismus feel often derided. Wearing spectacles is considered
      by them as an additional burden. The resulting emotional problems were apparent
      in a study of their drawings and accompanying interviews 12 years ago. Although
      interviews showed a year ago that the spectacles were better accepted, they still
      do not seem to be "interiorised". Therefore parents should emphasize the positive
      aspect of wearing spectacles, which should be considered as an ornament.

PMID- 7633632
TI  - Deteriorated accommodative esotropia.
AB  - Deteriorated accommodative esotropia is a residual esotropia with treatment in
      previously controlled esotropia. Hypothesized etiologies include occlusion,
      undercorrected hyperopia, increased AC/A ratio, increased or undetected
      hyperopia, microtropia, delay in treatment and poor compliance.

PMID- 7633633
TI  - [Vertical deviation in strabismus in children].
AB  - Cyclovertical deviations represent a major diagnostic and therapeutic problem in
      strabology. In this paper 4 topics are discussed. Long term evolution of
      strabismus after surgery shows that the patient's residual threshold for a
      residual vertical factor is very weak; its correction is of the utmost
      importance. Indeed, if some degree of binocular vision is to be recovered, the
      residual vertical factor should not be greater than 4 D in esotropia. There are
      many different varieties of vertical deviation but 3 are particularly common:
      oblique muscles overactions, DVD and alphabetical syndromes. There are several
      arguments against sagittalization during oblique muscles development. The author
      then presents an epidemiological survey of vertical factors based on a randomized
      study of 1500 consecutive cases of strabismus. In the last section, the problem
      of vertical factors in accommodative strabismus is discussed; there are many
      arguments against Gobin and Berard's ideas on the role and management of optical
      correction in accommodative squint.

PMID- 7633635
TI  - [Photoscreening].
AB  - Photoscreening is a photographic method to determine whether a child's eyes focus
      properly or not. This method can be used from the moment the child is able to
      fix, which is around six months. Photoscreening allows us to detect a
      hypoaccommodation and to determine the minimal optical correction to prescribe.
      It is used to evaluate the postoperative position of the eyes and shows the
      dominant eye. This eye should be occluded intermittently in order to prevent
      amblyopia and/or a relapse of the squint.

PMID- 7633634
TI  - [The Leiden school].
AB  - Simultaneous horizontal and cyclovertical surgery gives better results than pure
      horizontal surgery; not only binocular vision reappears immediately and
      spontaneously but the accommodative component of the squint disappears as well.
      The question is to know why simultaneous surgery gives such good results. We
      think that the reduction of the vertical deviations associated with horizontal
      strabismus may give an explanation. In our experience, a vertical deviation is
      often present in accommodative strabismus and can disrupt fusion. The hemiretinal
      suppression which follows, puts the vergence system into open loop. The
      accommodative vergence caused by hypermetropia becomes manifest so that the
      correction needs to be reinforced frequently. In a young child this may impede
      the emmetropisation process. In addition, the spectacles being associated with
      strabismus, may be the source of psychological complexes. The fact that the
      squint is not cured and the deviation reappears without spectacles gives us the
      right to look for a more adequate remedy. The good results we obtained with
      simultaneous horizontal and cyclovertical surgery and especially the
      disappearance of the accommodative element encouraged us to operate accommodative
      strabismus.

PMID- 7633637
TI  - Membrane bilayer instability as a pathogenetic mechanism for neurological
      disease.

PMID- 7633638
TI  - Microencapsulation and the grafting of genetically transformed cells as
      therapeutic strategies to rescue degenerating neurons of the CNS.
AB  - A number of approaches have been developed to deliver growth factors within the
      central nervous system of adult mammals. Initially a variety of neurotrophic
      factors were administered either by single intracerebroventricular or local
      injections directly into brain tissues or via permanently installed cannulae for
      chronic administrations. More recently delivery systems including conjugates,
      biodegradable and non-biodegradable implants and microspheres as well as
      genetically engineered cells have been introduced in order to provide a prolonged
      supply of neurotrophic factors and to prevent their enzymatic degradation. In
      this review we examine a variety of means of delivering neurotrophic factors
      (mainly nerve growth factor) with the primary focus upon the use of
      microencapsulated neurotrophins and cells genetically modified to produce them.
      In addition, this review highlights some difficulties and future trends in the
      development of novel delivery systems hopefully more suitable for investigations
      in different areas of neuroscience.

PMID- 7633636
TI  - [Amblyopia due to ametropia].
AB  - The cause of amblyopia by ametropia is evaluated, hypoaccommodation plays an
      important role and also astigmatism. The treatment of hypermetropia by full
      spectacle correction is contested and the tests used to detect amblyopia and
      hypoaccommodation are described. The use of videorefraction and photoscreening is
      important in the follow-up of our patients.

PMID- 7633639
TI  - Aging and motor learning: a possible role for norepinephrine in cerebellar
      plasticity.
AB  - Norepinephrine is known to act as a neuromodulator in the cerebellar cortex
      because it can increase the effect of neurotransmitters such as GABA. This
      neuromodulatory effect of NE is a possible substrate for an effect of NE on
      cerebellar plasticity. Cerebellar plasticity can be examined by studying the
      learning of motor skills. A rod walking paradigm is used in our laboratory for
      such investigations. Learning of this rod walking task is impaired in rats that
      are depleted of central stores of NE and in rats that have received the beta
      adrenergic antagonist propranolol. In addition, in aged rats there is a
      correlation between the loss of beta-adrenergic receptor mediated neuromodulatory
      actions of NE in the cerebellum with a decreased ability to learn the rod walking
      task. Taken together this information supports a role for NE in cerebellar
      plasticity and suggest that the beta-adrenergic receptor is important for this
      plasticity.

PMID- 7633640
TI  - Neurotransmitters regulating feline aggressive behavior.
AB  - The experiments described in this review reveal that the expression and
      modulation of aggressive responses in the cat are organized by two distinct sets
      of pathways. One set of pathways is associated with the elicitation of a specific
      form of attack behavior. It includes the medial hypothalamus and its projections
      to the PAG for the expression of defensive rage behavior and the lateral
      hypothalamus and its descending projections for the expression of predatory
      attack behavior. The primary focus of the present review is upon the analysis of
      defensive rage behavior. It was demonstrated that the pathway from the medial
      hypothalamus to the PAG, which appears to be essential for elicitation of
      defensive rage, is powerfully excitatory and utilizes excitatory amino acids that
      act upon NMDA receptors within the PAG. The other pathways examined in this
      review arise from different nuclei of the amygdala and are modulatory in nature.
      Here, two facilitatory systems have been identified. The first involves a
      projection system from the basal complex of amygdala that projects directly to
      the PAG. Its excitatory effects are manifest through excitatory amino acids that
      act upon NMDA receptors within the PAG. The second facilitatory pathway arises
      from the medial nucleus of the amygdala. However, its projection system is
      directed to the medial hypothalamus rather than the PAG. Its neurotransmitter
      appears to be substance P that acts upon NK1 receptors within the medial
      hypothalamus (see Figure 10). It has yet to be determined whether substance P
      acts upon any of the other neurokinin receptor subtypes. It should also be
      pointed out that the substance P pathway from the medial amygdala to the medial
      hypothalamus functions to suppress predatory attack behavior elicited from the
      lateral hypothalamus. In this network, it is likely that the modulatory effects
      of the medial amygdala require the presence of a second, inhibitory pathway from
      the medial hypothalamus that innervates the lateral hypothalamus. At the present
      time, the neurochemical nature of this second pathway remains unknown, although
      it is suggested that such neurons may be GABAergic. One major inhibitory pathway
      was also identified. It arises principally from the central nucleus of the
      amygdala and projects to the PAG. Its powerful suppressive effects upon PAG
      elicited defensive rage behavior are mediated through opioid peptides that act
      upon mu receptors within the PAG. While the present series of studies have begun
      to define the structural and functional nature of the neural systems that
      regulate aggressive behavior, our understanding of the overall mechanisms
      regulating different forms of aggressive behavior remains incomplete.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7633641
TI  - Neural basis of saccade target selection.
AB  - Saccade target selection must be understood in relation to the obvious fact that
      vision naturally occurs in a continuous cycle of fixations interrupted by gaze
      shifts. The guidance of eye movements requires information about what is where in
      the visual field. The identities of objects are derived from their visible
      features. Single neurons in the visual system represent the presence of specific
      features by the level of activation; the reliability of the discriminating signal
      from single neurons varies over time. Each point in the visual field is
      represented by many populations of neurons activated by all types of features.
      Topographic representations are found throughout the visual and oculomotor
      systems; neighboring neurons tend to represent similar visual field locations or
      saccades. Selecting one out of many stimuli to which to direct gaze requires
      comparing stimulus attributes across the visual field. The existence of
      retinotopic maps of the visual field makes possible local interactions to
      implement such comparisons /41/. For example, a lateral inhibition network can
      extract the location of the most conspicuous stimulus in the visual field
      /30,40,81/. Coordinated with this parallel visual processing is activation in
      structures responsible for producing the movement such as FEF and the superior
      colliculus. A saccade is produced when the neurons at one location within the
      motor maps become sufficiently active. One job of visual processing, then, is to
      ensure that only one site within a movement map becomes activated. This is done
      when the neurons signalling the location of the desired target develop enhanced
      activation while the neurons responding to other locations are attenuated.
      Saccade target selection often converts an initially ambiguous pattern of neural
      activation into a pattern that reliably signals one target location. The
      ambiguity may be reduced through prior knowledge of the likely target location or
      identity, and extraretinal signals reflecting such expectations can modulate the
      responsiveness of afferent visual neurons. Specifying the metrics of a saccade
      and triggering the movement are coordinated but dissociable processes. Speed
      accuracy trade-offs can thereby be produced allowing the visuomotor system to
      produce a saccade that is inaccurate because it is premature relative to the
      target selection process. While there are many gaps in our knowledge, the
      questions to ask seem reasonably clear. Because saccade target selection involves
      visual processing and eye movement programming combined with mnemonic influences,
      only continued experimental ingenuity will disentangle the various and variable
      contributions of individual neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7633642
TI  - Laparoscopic sonography in screening metastases from gastrointestinal cancer:
      comparative accuracy with traditional procedures.
AB  - The wide use of operative and diagnostic laparoscopy has led to a greater use of
      the laparoscopic ultrasound (LUS) as a complementary procedure. A preliminary
      study was performed to evaluate the efficacy of LUS using a linear array
      laparoscopic probe characterized by double frequency, mechanical flexibility, and
      availability of Doppler analysis. LUS was performed in 36 patients with
      gastrointestinal neoplasms and compared with preoperative sonography, computed
      tomography, and with laparoscopy alone. LUS identified liver metastases with a
      sensitivity of 100% versus 60% for preoperative diagnostic means and laparoscopy.
      Nodal metastases were identified with a sensitivity of 96.1% and a specificity of
      66.6%. Therapeutic planning was modified as result of LUS in 8 of 35 cases
      (22.9%). In patients with abdominal malignancy, LUS improves staging (cancer
      spread, nodal metastases, liver metastases), modifying therapeutic decisions. LUS
      represents a complementary, indispensable diagnostic method during laparoscopic
      surgery.

PMID- 7633643
TI  - Extensive subcutaneous emphysema and hypercapnia during laparoscopic
      cholecystectomy: two case reports.
AB  - We report two cases of marked hypercapnia of more than 60 mm Hg (PaCO2) and
      extensive subcutaneous emphysema noted during laparoscopic cholecystectomy. The
      first case, a 55-year-old man was diagnosed as having cholecystolithiasis and had
      hypercapnia up to 83.5 mm Hg (PaCO2) during laparoscopic cholecystectomy. The
      patient resumed spontaneous respiration under controlled ventilation accompanied
      by persistent bigeminal pulse. Soon after deflation, CO2 returned to normal
      range, and extensive subcutaneous emphysema was detected in the recovery room.
      The second patient, a 53-year-old woman, had cholecystolithiasis and also
      underwent laparoscopic cholecystectomy. Both hypercapnia rising to 61.1 mm Hg
      (PaCO2) and extensive subcutaneous emphysema appeared just before completion of
      resection of the gallbladder. Mild hypercapnia during pneumoperitoneum of about
      50 mm Hg (PaCO2) has been reported previously. As compared with cases in the
      literature, the present cases suggest that hypercapnia is due to extensive
      subcutaneous emphysema. The large absorption surface area in the subcutaneous
      tissue and the large difference in the partial pressure cause the extensive
      gaseous interchange of CO2 between subcutaneous tissue and blood perfusing into
      it at the moment between peritoneal cavity and blood perfused the peritoneum.

PMID- 7633644
TI  - Intravenous cholangiography and the management of choledocholithiasis prior to
      laparoscopic cholecystectomy.
AB  - The preoperative diagnosis of choledocholithiasis simplifies the laparoscopic
      management of biliary tract disease. Slow infusion intravenous cholangiography
      (SI-IVC) may be an accurate and cost-effective screening test for
      choledocholithiasis, and it is safer than traditional intravenous
      cholangiography. Forty-nine patients underwent SI-IVCs for suspected
      choledocholithiasis. These patients subsequently had endoscopic retrograde
      cholangiograms (ERC) or intraoperative cholangiograms (IOC) during laparoscopic
      cholecystectomies. Sixteen SI-IVCs demonstrated choledocholithiasis; 13 were
      confirmed by ERCs or by IOCs. The remaining 33 patients with negative SI-IVCs had
      negative ERCs or IOCs. The sensitivity, specificity, and accuracy of detecting
      choledocholithiasis by SI-IVC were 100%, 92%, and 94%. Only one patient had a
      mild reaction to the contrast agent. In our hospital the cost of an SI-IVC is
      $324, the cost of an IOC is $393 (including operating room and anesthesia costs),
      and the cost of an ERC is $1,085. SI-IVC is an accurate method of preoperative
      screening for choledocholithiasis. It is safe and cost-effective.

PMID- 7633647
TI  - Thoracoscopic pericardiectomy.
AB  - A new technique for pericardial resection is described using thoracoscopy. With
      the advent of newer videolaparoscopic techniques allowing better visualization
      and the use of new endoscopic staplers, a whole spectrum of surgical procedures
      can now be performed through the thoracoscope.

PMID- 7633648
TI  - An alternative technique to create the pneumoperitoneum for laparoscopic surgery.
AB  - A method for creating the pneumoperitoneum for laparoscopic surgery in 200
      patients used the Lazarus-Nelson technique. A needle half the diameter of the
      Veress needle was used. A guide wire followed by a catheter with multiple side
      ports allowed for rapid infusion of CO2. A technique used safely in hundreds of
      thousands of peritoneal lavages gives the surgeon a safe and rapid technique to
      create a pneumoperitoneum.

PMID- 7633646
TI  - Laparoscopic cholecystectomy in obese patients compared with nonobese patients.
AB  - Obese patients treated by laparoscopic cholecystectomy currently appear to be the
      largest risk subgroup amenable to consistent scientific evaluation. Here we
      report our experience and compare the results in obese patients with those
      obtained in nonobese patients undergoing the laparoscopic procedure. Laparoscopic
      cholecystectomy in obese patients was technically more difficult with
      significantly longer operating time (p < 0.01), but intraoperative and
      postoperative technical complications were not significant in the groups
      analyzed. Obese patients present significant anesthesiological complications (p <
      or = 0.001). The results of this experience and the literature review indicate
      that the therapeutic advantages proved in nonobese patients can be extended to
      the obese population.

PMID- 7633645
TI  - Balloon dissection in extended retroperitoneoscopy.
AB  - The anatomy of the retroperitoneum, including the high retroperitoneum, was
      studied as it appears with balloon dissecting techniques. We used fresh cadavers
      in this study. A relatively unknown fascia that is located between the lateral
      aspect of the perirenal fascia and the posterior parietal peritoneum, called the
      paraconal fascia, was a constant finding. This structure is important because it
      protects delicate retroperitoneal organs: the duodenum, pancreas, celiac axis,
      and superior mesenteric artery. Locating this fascia is an important step in the
      dissection of the high retroperitoneum, which is of interest in advanced
      videoendoscopic procedures involving retroperitoneal organs.

PMID- 7633649
TI  - Laparoscopic Billroth I gastrectomy for gastric ulcer: technique and case report.
AB  - A laparoscopic distal gastrectomy with gastroduodenostomy (Billroth I) was
      performed on a patient with intractable gastric ulcer. The patient was a 56-year
      old man, complaining of severe epigastralgia, who had a 10-year history of peptic
      ulcer. Gastroscopy had revealed a UL-IV gastric ulcer on the lesser curvature at
      the angle of the stomach and a deformity of the bulbus. A diagnosis of
      intractable gastric ulcer was made, and the patient underwent laparoscopic distal
      gastrectomy and gastroduodenostomy. On postoperative day 1, he was able to walk.
      On postoperative day 4, he started on a clear liquid diet and was discharged on
      postoperative day 14.

PMID- 7633650
TI  - Intestinal obstruction--a procedure-related complication of laparoscopic inguinal
      hernia repair.

PMID- 7633651
TI  - Laparoscopic-assisted perineal rectosigmoidectomy for rectal prolapse.
AB  - One of the important surgical principles in perineal rectosigmoidectomy
      (Altemeier's procedure) for full-thickness rectal prolapse is to ensure the
      complete resection of the redundant rectosigmoid colon to avoid recurrence of the
      prolapse. We present a new technique of laparoscopic assistance during this
      procedure, which helps achieve maximal mobilization and resection of the
      prolapsed portion.

PMID- 7633652
TI  - Perforation of the gallbladder and spilled gallstones during laparoscopic
      cholecystectomy.

PMID- 7633653
TI  - Estimation of the proliferative activity of human breast cancer tissue by means
      of the Ki-67 and MIB-1 antibodies--comparative studies on frozen and paraffin
      sections.
AB  - The estimation of the Ki-67 index in human breast cancer tissue has been proven
      to be a useful prognostic tool. The examination can be performed, however, only
      on frozen sections (FS). The development of an antibody directed against parts of
      the Ki-67 antigen (MIB-1) has opened a new route to determine the proliferative
      activity on paraffin sections (PS). MIB-1 immunohistochemistry is used instead of
      Ki-67 immunohistochemistry if a tumour is delivered to the pathologist after
      formalin fixation or if that part of the tissue suspicious for breast cancer must
      be totally embedded in order to confirm the diagnosis. The present study compares
      the findings of Ki-67 (FS) and MIB-1 (FS and PS) immunohistochemistry in a total
      of 544 cases of human breast cancer. The findings confirm a good statistical
      correlation between the Ki-67 and the MIB-1 findings. The MIB-1 results are 2-2.5
      times higher in FS than in PS. Good agreement exists between the Ki-67 indices
      determined on FS and the MIB-1 indices determined on PS. If the cut-off value for
      the separation of Ki-67 negative and positive cases is defined as 10%-20%, a MIB
      1 index in PS of 10% permits the correct prediction of a negative Ki-67 index in
      97% of the cases, and a MIB-1 index of 30% or more correctly predicts a positive
      Ki-67 index in 90% or more of the cases. Hence, the determination of the MIB-1
      index on PS may replace the determination of the Ki-67 index on FS with a high
      degree of probability.

PMID- 7633654
TI  - Frequent loss of heterozygosity at the deleted in colorectal carcinoma gene locus
      and its association with histologic phenotypes in breast carcinoma.
AB  - Loss of heterozygosity (LOH) at the deleted in colorectal carcinoma gene (DCC), a
      tumour suppressor gene that encodes a protein with high homology to the neural
      cell adhesion molecule, was investigated in 42 surgical specimens of primary
      breast carcinoma. LOH was analysed in breast carcinoma by amplifying the DNA,
      spanning a variable number of tandem repeats site and a restriction fragment
      length polymorphism site within DCC, using the polymerase chain reaction (PCR).
      Cell sorting was used to enrich carcinoma cells. The expression of the DCC gene
      was also investigated using a reverse transcription-PCR method followed by
      Southern blot hybridization. LOH at the DCC locus was detected in 15 (51.7%) of
      29 informative cases and 10 of 13 cases having DCC-LOH showed distinct reduction
      or loss of DCC expression. The DCC-LOH was closely associated with certain
      histological phenotypes: DCC-LOH was more frequent in scirrhous carcinomas than
      in solid-tubular ones (P < 0.05), and was also more frequent in carcinomas with
      infiltration into fat tissue over the mammary gland than in those without
      infiltration (P < 0.05). DCC-LOH was detected in invasive lobular carcinomas
      (2/2), but in none of the noninvasive ductal carcinomas (0/2). These observations
      suggest that malignant histological phenotypes are associated with DCC-LOH.

PMID- 7633656
TI  - Immunohistochemical expression of C-myc oncogene, heat shock protein 70 and HLA
      DR molecules in malignant cutaneous melanoma.
AB  - The clinical course of malignant melanomas is frequently unpredictable, although
      a number of prognostically useful variables can be identified. There is a need
      for additional markers of prognostic value. In a series of 60 malignant cutaneous
      melanomas, we analysed the immunohistochemical expression of c-myc proto
      oncogene, heat shock protein 70 (HSP70) and HLA-DR molecules in order to
      investigate their prognostic significance. C-myc, HSP70 and HLA-DR were expressed
      in 43.3%, 56.6% and 38.3% of all melanoma cases, respectively. Advanced Clark
      levels (Clark III-V) were significantly associated with c-myc expression rate (P
      < 0.05), HSP70 detection (P < 0.01) and HLA-DR positivity (P < 0.01). Increased
      Breslow thickness (> 1.5 mm) was related to HLA-DR expression (P < 0.05). High
      mitotic rate was closely associated with c-myc positivity (P < 0.05), while HSP70
      and HLA-DR expression separately correlated to clinical stage of the disease (P <
      0.05). The evaluation of these variables may be of immunological and prognostic
      significance. They were found to be associated with melanocyte subpopulations of
      the vertical growth phase which are arguably characterized by an increased
      invasive potential.

PMID- 7633657
TI  - Culturing of cells from giant cell tumour of bone on natural and synthetic
      calcified substrata: the effect of leukaemia inhibitory factor and vitamin D3 on
      the resorbing activity of osteoclast-like cells.
AB  - Osteoclastic cells from giant cell tumour of bone (GCT) of bone provide a rich
      source for investigation of cellular mechanisms leading to formation of
      multinucleated cells, the resorption process and involvement of hormones and
      cytokines in these events. In the present study we investigated the effect of
      1,25-dihydroxyvitamin D3 (VD3) and leukaemia inhibitory factor (LIF) on the
      resorbing potential of osteoclast of GCT origin using quantitative image-analysis
      of resorption lacunae in an in vitro dentine model. While VD3 unsignificantly
      increased the number of resorption pits and implicated surface after 7 days of
      GCT cell culturing, the stimulative effect of LIF was statistically significant.
      In cultures supplemented with LIF (5000 U/ml) the number of lacunae and
      resorption surface increased by 38% and 55%, respectively, when compared with
      control cultures. We suggest that both osteotropic agents increased osteoclastic
      activity, as the number of multinucleated cells was similar in control and
      experimental cultures. Seeding of GCT cells on biphasic calcium phosphate
      substratum revealed the relative inability of osteoclastic cells to resorb this
      synthetic material.

PMID- 7633655
TI  - Frequency and spectrum of p53 mutations in gastric cancer--a molecular genetic
      and immunohistochemical study.
AB  - The p53 tumour-suppressor gene plays an important role in gastric carcinogenesis.
      In an analysis of the spectrum of mutations of the p53 gene seen in 56 primary
      gastric carcinomas of various types and grades of differentiation, the entire
      coding sequence (exons 2-11) of the p53 gene was screened by single-strand
      conformation polymorphism analysis and direct genomic sequencing of polymerase
      chain reaction products. Intragenic restriction site polymorphisms and the probe
      YNZ22 were used for the detection of loss of heterozygosity (LOH) of the p53 gene
      locus on chromosome 17p. p53 overexpression was studied with the anti-p53
      antibody CM-1. A total of 21 somatic alterations of the p53 gene were found.
      Twenty were base-pair substitutions, and one was an eight base-pair deletion. Six
      tumours with p53 mutations revealed LOH. Abnormalities in p53 expression were
      found in 17 tumour samples, of which 16 had gene mutations. The spectrum of
      mutations observed was consistent with the predicted spectrum for dietary
      mutagens associated with the metabolism of nitrogenous compounds, resulting in
      deamination of nucleic acids. Our findings suggest that p53 could be a primary
      target for mutations associated with dietary carcinogens in gastric
      carcinogenesis.

PMID- 7633658
TI  - Morphology of cardiac muscle in septic shock. Observations with a porcine septic
      shock model.
AB  - The morphology of cardiac muscle was investigated in a porcine model of septic
      shock, created by intermitted application of Escherichia coli-endotoxin. The
      earliest lesions, found after 18 h of septic shock, were endothelial cell
      swelling, marked leucostasis and slight ischaemic alterations of the muscle
      fibres. At the end point of the experiments, after 48 h, some fibrin thrombi were
      found associated with more pronounced ischaemic alterations of cardiac muscle
      cells and some necrotic fibres. Comparing these findings with the severe
      endothelial and muscle fibre lesions found in skeletal muscle, the endothelial
      cells of the heart microvasculature, are clearly more resistant to the attack of
      the endotoxins and mediators liberated in septic shock.

PMID- 7633659
TI  - A histological study on experimental autoimmune myocarditis with special
      reference to initiation of the disease and cardiac dendritic cells.
AB  - The precise mechanism of myosin-induced autoimmune myocarditis is unknown. The
      purpose of the present study was to define the immunohistological and
      ultrastructural characteristics of the infiltrating cells, especially in the
      initial phase of the myocarditis. It was demonstrated that OX6-positive dendritic
      cells first infiltrated the cardiocytes on day 13 after immunization. After day
      17, OX6-positive cells, which possessed elongated irregular-shaped processes on
      the cell surface but contained few phago-lysosomes in the cytoplasm, were located
      at the margin of an inflammatory field and inserted their processes into the
      sarcoplasm of cardiocytes. The central portion of the inflammatory field was
      occupied by ED1-positive inflammatory macrophages, which were rich in phagosomes
      and which were in contact with degenerating cardiocytes. No evidence was obtained
      which suggested that lymphocytes directly injured the cardiocytes. These results
      demonstrated ultrastructural evidence that the type of infiltrating cell that
      first injures cardiocytes is the cardiac dendritic cell. Inflammatory macrophages
      thereafter serve as scavengers of degenerating cardiocytes.

PMID- 7633660
TI  - The small intestine in experimental diabetes: cellular adaptation in crypts and
      villi at different longitudinal sites.
AB  - Intestinal adaptation at the cellular level was examined in groups of
      streptozotocin-diabetic and age-matched control rats. Small intestines were
      removed and divided into four segments of roughly equal length. For each segment,
      epithelial volume, villous and microvillous surface areas and the mean volumes of
      epithelial cells in crypts and villi were estimated. From these data, we were
      able to estimate total numbers of epithelial cells in crypts and villi, assess
      adaptation at the level of the average cell and explore variation along the crypt
      villus axis, between segments and between groups. Whilst the villus:crypt cell
      ratio did not change, diabetic animals contained about 80% more epithelial cells
      than control rats. The morphophenotype of villous epithelial cells (represented
      by nuclear volume, cell height, area and volume, and number and surface area of
      microvilli) was basically the same as that in controls. By contrast, crypt cells
      and their nuclei were 40-50% bigger in diabetic rats. Significant differences
      between segments were confined to the numbers and sizes of crypt cells and their
      nuclei. We conclude that experimental diabetes leads to both proliferative and
      hypertrophic responses within crypts. Crypt cells become fatter but not taller.
      Crypt hyperplasia is accompanied by an equiproportionate increase in villous
      epithelial cells, but these are of essentially normal morphophenotype.

PMID- 7633662
TI  - A case report of synovial sarcoma with translocation (X;18). Application of
      fluorescence in situ hybridization to paraffin-embedded tissue.
AB  - A 57-year-old female patient with synovial sarcoma in her right foot had a
      chromosome abnormality defined as translocation (X;18). The tumour was located in
      the subcutis, and histological investigation showed monophasic proliferation of
      oval to spindle-shaped cells with a fascicular arrangement lacking an epithelial
      component. Immunostaining disclosed no cytokeratin or epithelial membrane antigen
      in tumour cells. Karyotypic analysis revealed translocation (X;18) in addition to
      other nonspecific aberrations. Fluorescence in situ hybridization was carried out
      on paraffin-embedded tissue, using DNA probes for the centromeres of chromosomes
      X and 18 with whole chromosome painting probes for X and 18. The free nuclei
      showed two signals at a rate of 83-85% with the X and 18 centromeric probes, in
      contrast to three signals at a rate of 68-70% with the X and 18 painting probes.

PMID- 7633663
TI  - Von Hippel-Lindau disease presenting as pancreatic neuroendocrine tumour.
AB  - A 21-year-old woman with a family history of von Hippel-Lindau disease presented
      with a mass in the head of the pancreas. Light microscopic features of the tumour
      suggested neuroendocrine differentiation and although it displayed positive
      immunostaining for the antigens expected in a neuroendocrine neoplasm, S-100
      staining was also present. This unusual feature prompted further evaluation by
      routine and post-embedding protein-A gold immunoelectron microscopy, which
      demonstrated the presence of neuroendocrine granules. Tumour cell DNA content was
      normal by flow cytometry. Although this patient exhibited no other signs of von
      Hippel-Lindau disease, the presence of a pancreatic tumour with neuroendocrine
      differentiation demonstrated that she was affected. Future surveillance and
      genetic counselling will be influenced by this diagnosis.

PMID- 7633661
TI  - Glomerular hypertrophy after subtotal nephrectomy: relationship to early
      glomerular injury.
AB  - Structural adaptations in response to approx. 70% nephrectomy were studied in
      male Sprague-Dawley rats. Rats developed systemic hypertension as well as
      progressive albuminuria after nephrectomy. At 18-26 weeks after nephrectomy (n =
      6) or sham treatment (n = 6) kidneys were perfusion-fixed and examined by light
      and electron microscopy. Glomerular tuft volume (+140%), capillary volume (+151%)
      and length (+77%), mesangial volume (+115%), podocyte volume (+96%), glomerular
      basement membrane surface area (+107%) and filtration slit length (+85%) were all
      significantly greater in nephrectomized rats. The incidence of segmental
      glomerular sclerosis was low and variable among these rats, but was significantly
      higher than in controls (P = 0.037). Urinary albumin excretion was elevated in
      the nephrectomized rats (89 +/- 72 SD mg/day vs 11 +/- 11 mg/day in control rats,
      P = 0.01) and correlated significantly with the incidence of sclerosis (r =
      +0.8311, P < 0.05). The relationships of the level of albuminuria and the
      sclerosis rate to various morphometric parameters were examined by regression
      analysis for the nephrectomy group. A significant negative correlation was found
      between albuminuria and average tuft volume (r = -0.8136) and glomerular basement
      membrane surface area (r = -0.8168). Both sclerosis rate and albuminuria showed
      negative correlations with filtration slit length (r = -0.8180 and r = -0.8598).
      These findings suggest that under some circumstances, glomerular hypertrophy may
      prevent or ameliorate the early stages of glomerular injury after subtotal
      nephrectomy.

PMID- 7633664
TI  - Urachal adenocarcinoma metastatic to the ovary simulating primary mucinous
      cystadenocarcinoma of the ovary: report of a case.
AB  - A 56-year-old woman had a large multicystic ovarian tumour 4 years after
      undergoing partial cystectomy for a deeply invasive urachal adenocarcinoma. On
      microscopic examination the ovarian tumour was a moderately differentiated
      mucinous cystadenocarcinoma similar to the urachal tumour. Several peritoneal
      biopsies and the omentum were positive for metastatic adenocarcinoma. Although
      initially interpreted as representing primary mucinous adenocarcinoma of the
      ovary with peritoneal spread, subsequent comparison with the previous urachal
      adenocarcinoma led to re-interpretation of the ovarian tumour as metastatic
      urachal carcinoma. Metastatic mucinous adenocarcinomas involving the ovary may be
      misinterpreted as primary ovarian carcinomas and the urinary bladder is a
      potential source of these neoplasms.

PMID- 7633667
TI  - Simplified cryopreservation of mammalian cell lines.

PMID- 7633665
TI  - Ovarian sertoliform endometrioid carcinoma.
AB  - Sertoliform endometrioid carcinoma (SEC) is a rare ovarian neoplasm occurring
      almost exclusively in post-menopausal patients. We studied a 71-year-old patient
      who underwent a total hysterectomy with bilateral salpingo-oophorectomy for a
      right ovarian mass measuring 25 cm in its maximal dimension. Histology revealed
      an SEC, featuring foci of typical endometrioid carcinoma and areas of clear cell
      differentiation. This particular type of ovarian neoplasm, already described in
      21 reported cases in the literature, must be distinguished from Sertoli cell
      tumours and Sertoli-Leydig cell tumours which are encountered at a younger age.
      We discuss the elements of the differential diagnosis and insist upon the value
      of anti-epithelial membrane antigen in identifying an SEC.

PMID- 7633666
TI  - Aurintricarboxylic acid prevents vascular endothelial cell death.

PMID- 7633668
TI  - Retinal pigment epithelial cell support of photoreceptor survival in vitro.

PMID- 7633669
TI  - Isotonic sucrose improves cryopreservation of cultured mammalian cells.

PMID- 7633670
TI  - Culture of human esophageal endoscopic biopsies.

PMID- 7633671
TI  - Extended liver-specific functions of porcine hepatocyte spheroids entrapped in
      collagen gel.
AB  - The potential use of porcine hepatocytes in a bioartificial liver device requires
      large quantities of viable and highly active cells. To facilitate the scaling up
      of the system, liver specific activities of hepatocytes should be maximized. One
      way of enhancing the specific activities is to cultivate hepatocytes as
      multicellular spheroids. Freshly isolated porcine hepatocytes form spheroids when
      cultivated in suspended cultures. These spheroids exhibit higher activities for a
      number of liver specific functions compared to hepatocytes cultivated as
      monolayers. However, these activities decreased in a few days in culture.
      Entrappment of spheroids in collagen gel sustained their metabolic activities at
      a stable level over 21 days. Production of albumin and urea by spheroid
      hepatocytes entrapped in collagen gels were 2 to 3 times higher than those by
      freshly isolated single cells. P-450 activity was demonstrated by metabolism of
      lidocaine to its main metabolite, monoethylglycinexylidide. Phase II drug
      metabolism was demonstrated by glucuronidation of 4-methylumbelliferone. This
      work shows that porcine hepatocyte spheroids entrapped in collagen maintain
      differentiated functions for an extended time period. Such hepatocyte spheroid
      entrappment system may facilitate the development of a bioartificial liver
      support device.

PMID- 7633672
TI  - Efficient lipid-mediated transfection of DNA into primary rat hepatocytes.
AB  - Cationic lipids are an effective means for transfecting nucleic acids into a
      variety of cell types. Very few of these lipids, however, have been reported to
      be effective with primary cells. We report on the efficacy of several
      commercially available cationic lipid reagents to transfect plasmid DNA into
      primary rat hepatocytes in culture. The reagents tested in this study include
      TransfectAce, LipofectAmine, Lipofectin, N-[1-(2,3-dioleyloxy)propyl]-n,n,n
      trimethylammoniumchloride (DOTMA), (N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethyl
      ammonium methylsulfate (DOTAP), and cetyltrimethyl-ammonium
      bromide/dioleoylphosphatidylethanol-amine (CTAB/DOPE). Electron micrographic (EM)
      studies indicate that similar size Lipofectin and DOTAP vesicles contain DNA-like
      material internally and that these vesicles attach to the cell membrane. DOTAP
      vesicles are multilamellar, appear as clusters, and have a high DNA-to-lipid
      ratio. Lipofectin vesicles appear to attach to the cell surface as individual
      vesicles. The EM observations are consistent with current theories on the
      mechanism of transfection by cationic lipids. While Lipofectin has proven to be
      effective in transfection studies of primary cells in culture, we have found
      DOTAP to be a viable alternative. DOTAP yields transfection rates in hepatocytes
      comparable to DOTMA and Lipofectin, however, at lower concentrations of reagent
      and at considerably less cost. Optimal conditions for transfecting 5 micrograms
      of plasmid DNA with DOTAP were achieved by utilizing multilamellar (vortexed)
      vesicles at a concentration of 15 micrograms DOTAP per 2 ml media in 60-mm plates
      for 2 h transfection time. In this study, DOTAP has proven to be economical, easy
      to prepare, and very effective in transfecting DNA into primary rat hepatocytes.

PMID- 7633674
TI  - Extracellular matrix interactions. 1: Production of extracellular matrix with
      attachment and growth-sustaining functions by UWOV2 ovarian cancer cells growing
      in protein-free conditions.
AB  - Constitutive production of extracellular matrix with attachment and growth
      promoting effects by an ovarian cancer cell line (UWOV2 (Pf)) growing in entirely
      protein-free conditions is described. This extracellular matrix has an ordered
      fibrillar, network structure consisting mainly of type IV collagen and laminin,
      as well as containing hyaluronan, glycoproteins, and proteoglycans. Type IV
      collagen appears to provide mainly structural support while other matrix
      components are responsible for the attachment and growth-promoting effects. This
      culture system provides an ideal model for studying the effects of extracellular
      matrix on cell attachment and growth. This system is also important in studying
      the concept of autonomous growth because the production of extracellular matrix
      by these cells appears to be growth regulatory even in an entirely protein-free
      culture system.

PMID- 7633675
TI  - Extracellular matrix interactions. 2: Extracellular matrix structure is important
      for growth factor localization and function.
AB  - The influence of extracellular matrix components and of extracellular matrix
      structure on in vitro cell growth was investigated in the UWOV2 (Pf), protein
      free cell culture model. This cell line constitutively produces an ordered
      extracellular matrix in the absence of any exogenous protein or growth factor.
      Extracellular matrix from UWOV2 (Pf) cells was found to contain both transforming
      growth factor beta (TGF beta) and platelet-derived growth factor (PDGF), which
      were shown to have an autostimulatory role for UWOV2 (Pf) cell growth. Matrix
      structure was shown to be important for allowing expression of the functional
      activity of these two growth factors. In addition, a nonuniform distribution of
      PDGF, embedded within the matrix structure, was demonstrated by
      immunoelectronmicroscopy. Apart from these two well-defined growth factors,
      additional but as yet unidentified growth stimulatory factor(s) were extractable
      from UWOV2 (Pf) extracellular matrix. These investigations indicate the potential
      role of extracellular matrix both as a mechanism for concentrating as well as
      modulating the function of cellular growth factors.

PMID- 7633673
TI  - Expression of airway secretory epithelial functions by lung carcinoma cells.
AB  - We examined 12 non-small cell lung carcinoma cell lines for expression of airway
      goblet, serous, and mucous cell characteristics. The cells expressed some
      ultrastructural traits of secretory epithelial cells but none contained secretory
      granules typical of the airway secretory cells. Using immunocytochemistry and
      cell-specific monoclonal antibodies, we identified heterogeneous expression of
      goblet, mucous, and serous cell markers among the cell lines. After metabolic
      radiolabeling, cells incorporated isotope into high molecular weight material.
      Incubation of pulse-radiolabeled cells with a number of known mucus secretogogues
      revealed that 5 of the 12 cell lines released radiolabeled material in response
      to the agonists. However, in each cell line only one of the receptor-activated
      pathways tested was intact. Although we did not identify a single cell line
      expressing a phenotype similar to normal airway secretory cells, particular
      functions retained by some of these cell lines may make them useful for specific
      studies of mucus production or secretion.

PMID- 7633678
TI  - [Answering the demand for continuing education].

PMID- 7633677
TI  - [Can one develop within the hospital?].

PMID- 7633679
TI  - [Adaptation to the work place. Proposal of a system of education].

PMID- 7633681
TI  - [The teacher from outside the hospital: mediator and connector].

PMID- 7633680
TI  - [From the executive organism to the partnership organism. Considerations on the
      ties between the continuing education organism and its client].

PMID- 7633676
TI  - Insulinlike growth factor-1 (IGF-1)-induced stimulation of porcine preadipocyte
      replication.
AB  - Insulinlike growth factor-1 (IGF-1) is both adipogenic and mitogenic to
      preadipose cell lines as well as primary stromalvascular (SV) cells. The precise
      effect of IGF-1 on primary preadipocytes per se, however, has not been elucidated
      directly. In this study, primary porcine preadipocytes were exposed to IGF-1
      while at three culture densities. The proportion of replicating preadipocytes was
      determined by labeling cells with an antiadipocyte/preadipocyte monoclonal
      antibody (MAb) concomitant with DNA measurement with propidium iodide. Flow
      cytometric analysis revealed that different seeding densities did not affect the
      relative proportion of preadipocytes (AD-1 positive) in cultures. However, IGF-1
      treatment increased the proportion of preadipocytes at all densities but to a
      greater extent in more dense cultures. The resultant number of fat cell clusters
      formed was greater at higher densities and on IGF-1 treatment. The proportion of
      replicating cells in cultures decreased with increasing density. IGF-1
      significantly increased replication at all densities and increased the number of
      replicating preadipocytes to the same extent independent of density. These
      results provide direct evidence of hormonal regulation of primary preadipocyte
      replication.

PMID- 7633682
TI  - [The IFSI and continuing education].

PMID- 7633683
TI  - [Nursing research?].

PMID- 7633684
TI  - [What memories of nursing school for what nursing research?].

PMID- 7633686
TI  - [Supporting students at the IFSI].

PMID- 7633685
TI  - [Continuing education. Some reference points].

PMID- 7633687
TI  - [Malaise in a predominantly feminine profession. The threshold and the flaw].

PMID- 7633688
TI  - [Letter of a patient to her physician].

PMID- 7633689
TI  - [Education and taming].

PMID- 7633690
TI  - [Policies for continuing education at the Senlis Hospital Center].

PMID- 7633691
TI  - Local nasal immunotherapy. Has the time come?

PMID- 7633692
TI  - Critical care in the pregnant patient.

PMID- 7633693
TI  - Nasal immunotherapy to Parietaria: evidence of reduction of local allergic
      inflammation.
AB  - Studies over 10 yr have demonstrated local nasal immunotherapy (LNIT) to be an
      effective treatment for rhinitis due to pollens and mites. The aim of our work
      was to investigate the effects of LNIT on the local inflammatory phenomena,
      employing the model of nasal allergenic challenge, since no evidence has been yet
      provided about LNIT effects on the events due to allergic reactions. We
      evaluated, in addition, the possible effects of LNIT on some systemic immunologic
      parameters and its clinical efficacy. The study involved a double-blind, placebo
      controlled trial of preseasonal immunotherapy with Parietaria in 20 adults. A
      significant reduction of symptoms, inflammatory infiltration, and intercellular
      adhesion molecule-1 (ICAM-1) expression on epithelial cells after nasal challenge
      was evidence as long-lasting effect. No changes in serum allergen-specific IgE,
      IgG, and soluble eosinophil cationic protein were detected, whereas an unexpected
      increase of soluble ICAM-1 was found in the placebo group only. The treatment was
      well tolerated and a significant clinical improvement under natural allergenic
      exposure was observed in the active group. The present study provides, for the
      first time, evidence that LNIT is able to modulate the nasal allergic
      inflammation.

PMID- 7633694
TI  - Effects of an antibody to interleukin-5 in a monkey model of asthma.
AB  - To investigate the role of interleukin-5 (IL-5) on airway hyperreactivity and
      pulmonary inflammation in nonhuman primate airways, the effect of a neutralizing
      monoclonal antibody to murine IL-5 (TRFK-5) was investigated in a cynomolgus
      monkey model of allergic asthma. Anesthetized Ascaris-sensitive monkeys underwent
      bronchoalveolar lavage (BAL) to assess the granulocyte content of this fluid
      before and 24 h after aerosolized Ascaris suum extract inhalation. Airway
      reactivity was assessed by the concentration of inhaled histamine required to
      produce a 40% reduction in dynamic lung compliance (Cdyn40). Exposure to A. suum
      extract produced an increase in airway reactivity (Cdyn40 = 0.065 +/- 0.024%
      before Ascaris; Cdyn40 = 0.014 +/- 0.004% after Ascaris) and an inflammatory
      reaction in the airways characterized by an increase in BAL eosinophils (0.05 +/-
      0.03 x 10(3) cells/ml before Ascaris; 176 +/- 76 x 10(3) cells/ml after Ascaris)
      and neutrophils (3 +/- 1 x 10(3) cells/ml before Ascaris; 406 +/- 211 x 10(3)
      cells/ml after Ascaris). In contrast, only small nonsignificant changes in airway
      reactivity and granulocyte influx into the BAL occurred after aerosolized saline
      as a sham challenge. When the monkeys were treated 1 h before Ascaris challenge
      with the TRFK-5 antibody (0.3 mg/kg, intravenously), there was no increase in
      airway reactivity after Ascaris challenge (Cdyn40 = 0.032 +/- 0.016% before
      Ascaris; Cdyn40 = 0.217 +/- 0.196% after Ascaris) and there were only small
      increases in the number of eosinophils and neutrophils in the BAL after Ascaris
      challenge. The inhibition of this pulmonary eosinophilia and bronchial
      hyperresponsiveness by TRFK-5 was seen for up to 3 mo after treatment.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7633695
TI  - Effects of nasal CPAP on sympathetic activity in patients with heart failure and
      central sleep apnea.
AB  - We hypothesized that (1) patients with congestive heart failure (CHF) and Cheyne
      Stokes respiration with central sleep apnea (CSR-CSA) would have greater
      nocturnal urinary and daytime plasma norepinephrine concentrations (UNE and PNE,
      respectively) than those without CSR-CSA because of apneas, hypoxia and arousals
      from sleep and (2) attenuation of CSR-CSA by nasal continuous positive airway
      pressure (NCPAP) would reduce UNE and PNE concentrations. Eighteen patients with
      and 17 without CSR-CSA (Non-CSR-CSA group) were studied. Left ventricular
      ejection fraction was similar in the two groups, but overnight UNE and awake PNE
      concentrations were greater in the CSR-CSA group (30.2 +/- 2.5 nmol/mmol
      creatinine and 3.32 +/- 0.29 nmol/L) than in the Non-CSR-CSA group (15.8 +/- 2.1
      nmol/mmol creatinine, p < 0.005, and 2.06 +/- 0.56 nmol/L, p < 0.05,
      respectively). Patients with CSR-CSA were randomized to a control group or to
      nightly NCPAP for 1 mo. CSR-CSA was attenuated in the NCPAP but not in the
      control group. The NCPAP group experienced greater reductions in UNE and PNE
      concentrations (-12.5 +/- 3.3 nmol/mmol creatinine and -0.74 +/- 0.40 nmol/L)
      than did the control group (-1.3 +/- 2.8 nmol/mmol creatinine, p < 0.025 and 1.16
      +/- 0.66 nmol/L, p < 0.025, respectively). In conclusion, in patients with CHF,
      CSR-CSA is associated with elevated sympathoneural activity, which can be reduced
      by NCPAP.

PMID- 7633696
TI  - Anti-tumor necrosis factor-alpha prevents decreased ventricular contractility in
      endotoxemic pigs.
AB  - It is not known how the decrease in left ventricular contractility following
      endotoxin exposure is mediated, or whether this decrease is preventable by
      antibodies to tumor necrosis factor-alpha (TNF alpha). Four groups of six
      anesthetized and instrumented pigs were pretreated with ovine polyclonal antibody
      to human TNF alpha (anti-TNF alpha), nonspecific IgG, or saline, and then treated
      with either endotoxin or saline. We measured hemodynamics and left ventricular
      pressures (Millar catheter) and volumes (conductance catheter). Left ventricular
      contractility was assessed using the slope (Emax) of the end-systolic pressure
      volume relationship. Four hours after the start of endotoxin infusion in the
      nonspecific IgG pretreated group, Emax had decreased by 44 +/- 6% (p < 0.05),
      mean arterial pressure had decreased from 115 +/- 7 mm Hg to 70 +/- 10 mm Hg (p <
      0.05), and cardiac output was rapidly decreasing after an initial increase (p <
      0.05). Anti-TNF alpha significantly reduced the decrease in Emax (11 +/- 9%, p <
      0.05), and the systemic hypotension (108 +/- 15 mm Hg to 99 +/- 6 mm Hg, p <
      0.05), at 4 h, and prevented the late decrease in cardiac output. This suggests
      that TNF alpha is an important early mediator in sepsis leading to decreased left
      ventricular contractility.

PMID- 7633697
TI  - Efficacy of expiratory tracheal gas insufflation in a canine model of lung
      injury.
AB  - Tracheal gas insufflation (TGI) improves the efficiency of CO2 elimination by
      reducing the CO2-laden dead space of the airways. The effect of TGI on PaCO2
      diminishes in the setting of acute lung injury (ALI) because an increased
      alveolar component dominates the total physiologic dead space. Nevertheless,
      adopting a strategy of permissive hypercapnia should partially offset the
      decreased efficacy of TGI by increasing CO2 concentration in the proximal
      airways. To examine these issues we studied the CO2 removal efficacy of
      expiratory TGI as an adjunct to conventional mechanical ventilation (CMV) before
      and after oleic acid-induced lung injury (OAI). We first examined the effect of
      TGI before and after OAI, keeping tidal volume (VT) and frequency constant, and
      allowing PaCO2 to increase after OAI. We then tested TGI efficiency after
      matching PaCO2 after OAI to its pre-OAI level by increasing VT (post-OA/VT
      stage). PaCO2 was 53 +/- 3, 79 +/- 21, and 52 +/- 4 mm Hg in the pre-OAI, post
      OAI, and post-OA/VT stages of CMV, respectively. The corresponding decrements in
      PaCO2 produced by TGI at a flow rate of 10 L/min were 16 +/- 3, 24 +/- 10, and 10
      +/- 2 mm Hg, respectively. TGI decreased total physiologic dead space per breath
      (VD) by 56, 31, and 28 ml during the pre-OAI, post-OAI, and post-OA/VT stages,
      respectively. Despite a smaller reduction in VD during the post-OAI stage, the
      effect of TGI on PaCO2 was preserved because of the relatively high PaCO2 prior
      to its initiation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7633698
TI  - Amrinone increases ventricular contractility and diastolic compliance in
      endotoxemia.
AB  - Systolic and diastolic dysfunction occur during human septic shock, and
      sensitivity to beta-adrenergic agents is reduced. We sought to determine whether
      amrinone, an inotropic agent independent of beta-receptors, increases left
      ventricular contractility or diastolic compliance after endotoxin infusion. We
      measured left-ventricular volume (using a conductance catheter) and pressure
      (using a Millar catheter) before and after administering amrinone (4.5 mg/kg
      i.v., then 10 micrograms/kg/min) to six endotoxemic and seven control pigs. The
      slope of the end-systolic pressure-volume relationship, Ees, was used as the
      primary measure of contractility. Diastolic stiffness was characterized using
      stiffness parameters taken from pressure-volume relationships (k) and from
      pressure-volume strain relationships. Amrinone increased Ees from a median of
      10.4 mm Hg/ml (interquartile range, 7.2 to 12.3) to 16.4 (13.7 to 18.6) (p <
      0.05) in the endotoxin group (p < 0.05). Amrinone decreased diastolic stiffness
      (k) in the endotoxin group by 35 +/- 18% (p < 0.05). Amrinone did not
      significantly change Ees or k in the control group. Mean arterial pressure
      decreased after endotoxin infusion from 117 +/- 23 mm Hg to 76.5 +/- 14.9 mm Hg
      (p < 0.05), and decreased further after amrinone to 62.0 +/- 14.8 mm Hg (p <
      0.05). We conclude that in this model of sepsis, amrinone may beneficially
      increase systolic contractility and diastolic compliance, but may dangerously
      decrease an already low mean arterial pressure.

PMID- 7633700
TI  - Regional control of venous return: liver blood flow.
AB  - The aim of the study was to determine whether closing pressures or vascular
      distensibility can be used to describe liver venous hemodynamics when right
      atrial pressure is raised. The study was performed using a vascularly isolated
      pig liver preparation that allowed the independent control of portal vein and
      hepatic artery inflows and of outflow pressure (Pout). Pressure-flow (P-Q)
      relationships of both liver vessels were generated at multiple levels of Pout. At
      Pout of 0 mm Hg, the portal vein P-Q relationship was linear, with a convexity
      toward the pressure axis at low flows (5 to 10 ml/min/kg). The zero flow pressure
      was 1.5 +/- 0.2 mm Hg, greater than Pout (p < 0.05). On raising Pout from 0 to 15
      mm Hg, the shape of the portal vein P-Q relationships became progressively more
      linear, with a decrease in slope; no difference between zero flow pressure and
      Pout was observed. At Pout of 0 mm Hg, the hepatic artery presented a zero flow
      pressure > Pout. Raising Pout from 0 to 15 and 30 mm Hg resulted in a zero flow
      pressure always > Pout (p < 0.05). The behavior of the liver vein system is
      characterized by a zero flow pressure mimicking a classic vascular waterfall and
      by distensibility, once the waterfall is exceeded. Both factors act to minimize
      the reduction in venous return with an increased central venous pressure. Flow
      through the hepatic artery is affected by an increase in backpressure occurring
      upstream from the sinusoids, reducing arterial inflow for a constant perfusion
      pressure.

PMID- 7633699
TI  - Effects of PEEP on liver arterial and venous blood flows.
AB  - Total venous return decreases with positive end-expiratory pressure (PEEP). It is
      likely that the liver plays an important role in this response, either through
      the development of an increase in venous resistance or through an increase in the
      venous backpressure at the outflow end of the liver. In addition, hepatic
      arterial flow is reported to be selectively decreased by the application of PEEP.
      Therefore, to clarify the effects of PEEP on liver hemodynamics, we generated
      pressure-flow (P-Q) relationships in both liver vascular beds of anesthetized,
      mechanically ventilated pigs at PEEP of 0, 5, 10, and 15 cm H2O to obtain values
      of backpressure (Pback, mm Hg) from linear extrapolation of the P-Q relationships
      and resistance (mm Hg/ml/min/kg) from its slope. PEEP decreased portal vein flow
      (Qpv) and caused an increase in the liver venous resistance (from 0.08 +/- 0.01
      to 0.16 +/- 0.02 mm Hg/ml/min/kg; p < 0.05). Ppvback and right atrial pressure
      (Pra) increased equally (from 5.1 +/- 0.3 to 9.9 +/- 0.4 mm Hg, p < 0.05, and
      from 4.0 +/- 0.2 to 8.6 +/- 0.5 mm Hg, p < 0.05, respectively, at PEEP 15). The
      reduction in portal venous flow was related to an increase in the backpressure to
      flow (as a result of an increase in Pra) and to an increase in liver venous
      resistances that may cause blood pooling in the splanchnic compartment and
      decrease venous return through the liver. PEEP increased Phaback (from 11.2 +/-
      0.9 to 14.5 +/- 0.7 mm Hg at PEEP 15, p < 0.05) but did not change hepatic
      arterial resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7633701
TI  - A randomized, double-blind comparison of methoxamine and epinephrine in human
      cardiopulmonary arrest.
AB  - The beneficial effect of epinephrine has been attributed to its alpha-adrenergic
      properties. The present study was designed to compare the effects of epinephrine
      and methoxamine in witnessed cardiac arrests. Consecutive, witnessed cardiac
      arrest victims presenting to the emergency room or from the inpatient population
      of our institution were enrolled in this study. Patients were randomized to
      receive either epinephrine (2 mg bolus followed by 2 mg every 4 min) or
      methoxamine (40 mg bolus followed after 4 min by 40 mg) in a blind design.
      Patients were followed prospectively for survival and neurologic outcome. A total
      of 199 patients were randomized into the study, but 54 had to be retrospectively
      dropped from analysis for failure to comply with the study protocol. Of the 145
      patients remaining, 77 received methoxamine (M) and 68 epinephrine (E). There was
      no difference in rate of successful resuscitation (42% versus 53%, M versus E,
      respectively), or in neurologic outcome as measured by the Glasgow-Pittsburgh
      Coma Score (GPCS). This study failed to demonstrate any difference in the rate of
      initial resuscitation, survival to discharge from the hospital, or neurologic
      status with methoxamine as opposed to epinephrine in the setting of cardiac
      arrest.

PMID- 7633702
TI  - Should mechanical ventilation be optimized to blood gases, lung mechanics, or
      thoracic CT scan?
AB  - This study was aimed at providing data for optimization of mechanical ventilation
      in patients with acute respiratory distress syndrome (ARDS). The effects of
      ventilation with positive end-expiratory pressure (PEEP) titrated to blood gases
      were studied by thoracic computed tomographic (CT) scans and lung mechanics
      measurements in eight patients. CT density histograms at end-expiration were used
      to investigate the effects of PEEP on three differently aerated zones. Static
      pressure-volume (P-V) curves were used to determine the deflection point above
      which baro-volotrauma (a combination of barotrauma and volotrauma) may occur.
      Peak pressures, plateau pressures, and lung volumes measured by Respitrace were
      compared with the deflection point. CT scan showed that PEEP increased "normally
      aerated" areas, decreased "nonaerated" areas, and did not change "poorly aerated"
      zones. No correlations were found between CT scan and either PaO2 or mechanical
      data. Pressure at the deflection point was lower than the usually recommended 35
      to 40 cm H2O for peak pressure in four patients (range, 28 to 32 cm H2O). With
      regard to plateau pressures, only one patient was ventilated above the deflection
      point. However, monitoring of volumes showed that these four patients had an end
      inspiratory volume above this point. We conclude that mechanical ventilation may
      be initially adjusted on the basis of blood gas values and then optimized on the
      basis of lung mechanics to limit the risk of baro-volotrauma.

PMID- 7633703
TI  - Alterations of lung and chest wall mechanics in patients with acute lung injury:
      effects of positive end-expiratory pressure.
AB  - In 16 mechanically ventilated patients with acute lung injury (ALI) (eight
      patients with moderate ALI [moderate group], eight patients with severe ALI
      [adult respiratory distress syndrome, ARDS group]) and in eight normal
      anesthetized-paralyzed subjects (control group), we partitioned the total
      respiratory system mechanics into the lung (L) and chest wall (w) mechanics using
      the esophageal balloon technique together with the airway occlusion technique
      during constant flow inflation. We measured lung elastance (Est,L), chest wall
      elastance (Est,w), and total lung (Rmax, L) and chest wall (Rmax,w) resistance.
      Rmax,L includes airway (Rmin,L) and "additional" lung resistance (DR,L). DR,L
      represents the "additional" component due to the viscoelastic phenomena of the
      lung tissues and time-constant inequalities (pendelluft). Measurements were
      repeated at 0, 5, and 10 cm H2O of positive end-expiratory pressure (PEEP) in the
      control group and at 0, 5, 10, and 15 cm H2O PEEP in patients with ALI. The end
      expiratory lung volume (EELV) was measured at each level of PEEP. Specific total
      lung (sRmax,L), airway (sRmin,L), and "additional" lung (sDR,L) resistances were
      obtained as Rmax,L x EELV, Rmin,L x EELV, and DR,L x EELV, respectively. At PEEP
      0 cm H2O, we found that both Est,L (23.7 +/- 5.5 and 13.8 +/- 3.3 versus 9.3 +/-
      1.7 cm H2O/L; p < 0.01) and Est,w (13.2 +/- 5.4 and 9.9 +/- 2.1 versus 5.6 +/-
      2.3 cm H2O/L; p < 0.01) were markedly increased in patients with ARDS and
      moderate ALI compared with control subjects, with a significant (p < 0.01) effect
      of the severity of the disease on Est,L (p < 0.01).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7633705
TI  - Etiology of extubation failure and the predictive value of the rapid shallow
      breathing index.
AB  - Failure of weaning from mechanical ventilation is thought to result from an
      imbalance between respiratory muscle capacity and respiratory demand. The ratio
      of respiratory rate to tidal volume (f/VT, rapid shallow breathing index) during
      spontaneous unsupported respiration increases when this imbalance exists, and may
      predict the success or failure of weaning from mechanical ventilation. Using
      f/VT, Yang and Tobin demonstrated a positive predictive value (PPV) of 0.78 (f/VT
      < or = 105 and weaning success) (1). To define the etiology of the 20% false
      positive rate (FPR, f/VT < or = 105 and weaning failure), 94 patients who had an
      f/VT determined prior to extubation were studied prospectively. Of 84 patients
      with an f/VT < 100, 14 required reintubation within 72 h of extubation (FPR =
      0.17, PPV = 0.83). Extubation in 13 of these 14 cases failed because of
      congestive heart failure, upper airway obstruction, aspiration, encephalopathy,
      or the development of a new pulmonary process. Only one patient needed
      reintubation solely because of the original respiratory process. Of 10 patients
      extubated with an f/VT > or = 100, four required reintubation, all because of the
      underlying respiratory process. This study confirms the high PPV for an f/VT <
      100. The FPR of approximately 0.20 is best explained by extubation failure caused
      by processes for which f/VT is physiologically or temporally unlikely to predict
      success or failure. The negative predictive value (f/VT > or = 100 but extubation
      success) for f/VT may be lower than previously reported.

PMID- 7633704
TI  - Nasal pressure support ventilation plus oxygen compared with oxygen therapy alone
      in hypercapnic COPD.
AB  - Non-invasive ventilation has been used in chronic respiratory failure due to
      chronic obstructive pulmonary disease (COPD), but the effect of the addition of
      nasal positive-pressure ventilation to long-term oxygen therapy (LTOT) has not
      been determined. We report a randomized crossover study of the effect of the
      combination of nasal pressure support ventilation (NPSV) and domiciliary LTOT as
      compared with LTOT alone in stable hypercapnic COPD. Fourteen patients were
      studied, with values (mean +/- SD) of Pao2 of 45.3 +/- 5.7 mm Hg, PaCO2 of 55.8
      +/- 3.6 mm Hg, and FEV1 of 0.86 +/- 0.32 L. A 4 wk run-in period (on usual
      therapy) was followed by consecutive 3-mo periods of: (1) oxygen therapy alone,
      and (2) oxygen plus NPSV in randomized order. Assessments were made during run-in
      and at the end of each study period. There were significant improvements in
      daytime arterial PaO2 and PaCO2, total sleep time, sleep efficiency, and
      overnight PaCO2 following 3 mo of oxygen plus NPSV as compared with run-in and
      oxygen alone. Quality of life with oxygen plus NPSV was significantly better than
      with oxygen alone. The degree of improvement in daytime PaCO2 was correlated with
      the improvement in mean overnight PaCO2. Nasal positive-pressure ventilation may
      be a useful addition to LTOT in stable hypercapnic COPD.

PMID- 7633706
TI  - Pulmonary infection during the acute respiratory distress syndrome.
AB  - Pulmonary infection is thought to be a common complication of ARDS. We undertook
      this prospective study to determine the incidence of pulmonary infection in
      patients with ARDS, and to evaluate the impact of nosocomial pneumonia on
      severity of ARDS and on survival. Two hundred one bronchoscopies were performed
      in 105 patients with ARDS with retrieval of distal airway secretions by
      bronchoalveolar lavage (BAL) and protected specimen brush (PSB). Whenever
      possible, bronchoscopy was performed at predetermined times: Day 3, Day 7, Day
      14, and Day 21 after the onset of ARDS. The majority of patients were receiving
      antibiotics at the time of study. Changes in bacterial flora over time were
      determined by quantitative cultures of BAL and PSB. Bacterial growth was common,
      but usually at small concentrations. Only 16 patients met quantitative culture
      criteria for pneumonia (PSB > or = 10(3) cfu/ml or BAL > or = 10(4) cfu/ml).
      Correlation was poor between clinical evidence of pneumonia and pneumonia by
      quantitative culture criteria: clinical criteria had a very low sensitivity (24%)
      for predicting positive quantitative culture results, and a low specificity (77%)
      for predicting negative quantitative culture results. There was no correlation
      between total colony counts on BAL or PSB and severity of ARDS as judged by
      Pao2/FIo2 ratios, days receiving ventilation, or compliance. Furthermore, there
      was no correlation between bacterial growth and survival. We conclude that
      pneumonia defined by quantitative bacteriology is uncommon in ARDS. The
      potentially confounding role of broad-spectrum antibiotics should be studied
      further.

PMID- 7633708
TI  - Racial differences in the association between maternal smoking during pregnancy
      and lung function in children.
AB  - We recently reported that suburban white schoolchildren whose mothers smoked
      during pregnancy have significantly reduced lung function. Because inner-city and
      minority children may be at greater risk for respiratory morbidity, we evaluated
      the relationship between maternal smoking during pregnancy and lung function in
      493 white and 383 black schoolchildren 9 to 11 yr of age in three areas of
      Philadelphia. The child's passive smoking history was determined from reports by
      the mother. Spirometry was performed at school. After adjusting for height,
      weight, age, sex, area of city, race, socioeconomic status, and current exposure
      to environmental tobacco smoke at home, maternal smoking during pregnancy was
      associated with significant deficits in FEF25-75 (-8.1%) and FEV1/FVC (-2.0%).
      The observed deficits were larger for black children than for white children, and
      they were larger for boys than for girls. These results provide additional
      evidence of an association between maternal smoking during pregnancy and reduced
      pulmonary function in children, and they suggest that the association may be
      modified by race and/or sex.

PMID- 7633707
TI  - "The sarcoidosis map": a joint survey of clinical and immunogenetic findings in
      two European countries.
AB  - We pooled immunogenetic data obtained in independent studies in two European
      populations (Italian and Czech) of patients affected by sarcoidosis.
      Correspondence analysis was used to investigate the associations between clinical
      and immunogenetic data. Two hundred and thirty-three patients were enrolled in
      the study, of which 126 were from the Czech Republic and 107 from Italy. Using a
      common protocol, we examined each patient for sex, age of disease onset,
      roentgenologic stage, extrapulmonary spread, and clinical course. One thousand
      and ten healthy individuals, HLA typed for class I and II serologic
      polymorphisms, served as controls. Findings that were essentially in agreement in
      both populations were: (1) a positive association of sarcoidosis with HLA-A1, B8,
      and DR3 markers, and a negative association with HLA-B12 and DR4; (2) a
      prevalence of HLA-DR3 and DR4 among females and of DR5 among males; (3) a
      relationship of B13 and B35 with early onset and of A30, B8, DR3, and DR4 with
      late onset of disease; (4) an association of B27 with sarcoidosis restricted to
      the lungs; (5) a relationship of A1, B8, B27, and DR3 to roentgenologic stage I
      and of B12 and DR4 to stage III; and (6) an association of HLA-DR3 with a good
      outcome. Population-restricted findings essentially concerned the alleles HLA-B13
      and B22, the former being associated with the disease, male sex, early onset,
      extrapulmonary localization and relapse only in Czechs, and the latter to disease
      spread only in Italians. Our results seem to support the concept that
      immunogenetic background may at least partly account for the clinical
      heterogeneity of sarcoidosis.

PMID- 7633709
TI  - Socioeconomic status and indicators of asthma in children.
AB  - Differential access and utilization of medical care by the poor and rich may
      contribute to differences in asthma prevalence. We therefore studied the
      relationship of socioeconomic status (SES) to various indicators of asthma in the
      Canadian context of universal access to medical care. Information on respiratory
      symptoms, demographics, and home exposures of 1,111 primary school children was
      collected by questionnaire. Parental occupation was used to establish SES.
      Exercise-induced bronchospasm (EIB) after a 6-min free-running test was our
      measure of airways responsiveness and was available for 989 children. As compared
      with children from the most advantaged homes, children from the least advantaged
      homes were more likely to present EIB (OR: 2.26, 95% CI: 1.12 to 4.58) and to
      report night cough (OR: 2.30, 95% CI: 1.04 to 5.06) and cough with mucus (OR:
      3.15, 95% CI: 1.06 to 9.33), while there was no significant excess of the report
      of wheeze or diagnosed asthma. Among factors potentially linked to SES, the
      presence of a cat at home (OR: 1.63, 95% CI: 1.02 to 2.61) and lower respiratory
      infection before 2 yr of age were associated with an excess of EIB (OR: 1.71, 95%
      CI: 1.16 to 2.52). Our results suggest that unidentified environmental factors
      contribute to the excess asthma morbidity in poor children.

PMID- 7633710
TI  - The effect of size and age of subject on airway responsiveness in children.
AB  - Methodologies used to assess airway responsiveness (AR) in children administer
      the same dosage schedule to all children despite the great range in the size of
      subjects. The aim of this study was to examine the hypothesis that the level of
      AR is size dependent within same-age cohorts and between different ages. Among a
      birth cohort of 1,037 New Zealand children participating in a longitudinal study,
      818 had at least two measurements of airway responsiveness between ages 9 and 15
      yr. Each child performed spirometry and a four-dose methacholine inhalation test.
      A continuous slope index of methacholine responsiveness was computed. AR slope
      indexes were analyzed using longitudinal methods, which included an indicator
      variable for subjects who reported having any wheeze. AR was lowest in both males
      and females in the upper quartile for height than those in the lower quartile,
      independently of age. AR tended to be higher (responded to lower concentrations
      of methacholine) in boys than girls and to decline with age among wheezers. The
      greater level of responsiveness in smaller or younger children could be explained
      by these individuals having received a dose of methacholine that was relatively
      large for their size.

PMID- 7633711
TI  - Long-term metered-dose inhaler adherence in a clinical trial. The Lung Health
      Study Research Group.
AB  - Poor adherence to medication regimens is a well-documented phenomenon in clinical
      practice and an ever-present concern in clinical trials. Little is known about
      adherence to inhaled medication regimens over extended periods. The present paper
      describes the 2-yr results of the Lung Health Study (LHS) program, which was
      developed to maintain long-term adherence to an inhaled medication regimen in
      3,923 special intervention participants (as measured by self-report and
      medication canister weight). The LHS is a double-blind, multicenter, randomized
      controlled clinical trial of smoking intervention and bronchodilator therapy
      (ipratropium bromide or placebo) for early intervention in chronic obstructive
      pulmonary disease (COPD). At the first 4-mo follow-up visit, nearly 70% of
      participants reported satisfactory or better adherence. Over the next 18 mo, self
      reported satisfactory or better adherence declined to about 60%. Canister weight
      classified adherence as satisfactory or better in 72% of participants returning
      all canisters at 1 yr, and in 70% of the participants returning all canisters at
      the 2-yr follow-up. Self-reporting confirmed by canister weight classified 48% of
      participants at 1 yr as showing satisfactory or better adherence. Overusers were
      50% more likely than others to misrepresent their true smoking status, suggesting
      that canister weights indicating overuse may be deceptive. Results of multiple
      logistic regression analysis indicate that the best compliance was found in
      participants who were married, older, white, had more severe airways obstruction,
      less shortness of breath, and fewer hospitalizations, and who had not been
      confined to bed for respiratory illnesses.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7633712
TI  - Proportion of moderately exercising individuals responding to low-level, multi
      hour ozone exposure.
AB  - The purpose of this study was to describe the proportion of moderately exercising
      individuals experiencing significant respiratory responses to low-level, multi
      hour ozone exposure as a function of ozone concentration and exposure duration.
      Sixty-eight healthy, nonsmoking adults, ages 18 to 34 yr, underwent two or more
      6.6-h exposures to 0.0, 0.08, 0.10, or 0.12 ppm ozone. Five hours of exercise was
      performed during exposure, and lung function was measured before exposure and
      following each hour of exposure. For each combination of concentration and
      duration, each individual was determined to either have or not have experienced a
      10% or greater decrement in FEV1. A logistic function was used to model the
      proportion of individuals experiencing such a decrement as a function of
      concentration and exposure duration. Bootstrap 90% confidence intervals (CIs)
      were calculated around the predictions. The model was found to give predictions
      that were in good agreement with observed data. The lowest level of exposure (C x
      T) for which the 90% CI excluded zero was approximately 0.2 ppm-h. For exposure
      to 0.12 ppm ozone for 6.6 h, 47% (90% CI = 30 to 65%) of exposed individuals were
      predicted to experience a 10% decrement in FEV1. A greater proportion of younger
      adults than of older adults were found to experience a given effect for a given
      exposure.

PMID- 7633713
TI  - Comparison of exogenous surfactants in the treatment of wood smoke inhalation.
AB  - The goal of this study was to compare the effectiveness of the exogenous
      surfactants Infasurf and Exosurf in reestablishing surfactant function inhibited
      by severe smoke inhalation. Mongrel dogs (n = 17) were anesthetized, placed on a
      ventilator (40% O2), and surgically prepared for hemodynamic and blood gas
      measurements; venous admixture (QVA/QT) and static lung compliance (Cstat) were
      calculated. At the conclusion of the experiment, lung samples were taken for lung
      water and dynamic surface tension (DST, Wilhelmy balance) measurements. Following
      baseline measurements, dogs were randomly separated into four groups: Group I,
      smoke+sham instillation; Group II, smoke+saline instillation: Group III,
      smoke+Exosurf instillation; and Group IV, smoke+Infasurf instillation. The
      surfactants (Infasurf and Exosurf, 100 mg/kg) or saline (same volume as
      surfactants) were instilled into the lungs via suction catheter immediately
      following smoke exposure. Smoke inhalation caused a similar increase in QVA/QT
      and fall in PaO2 and Cstat in all groups that improved only with Infasurf
      instillation (Group IV). DST was significantly improved by Infasurf compared with
      all other groups. We conclude that Infasurf restores normal DST, inhibited by
      wood smoke, improving lung function. Exosurf was ineffective in the treatment of
      wood smoke inhalation.

PMID- 7633714
TI  - The role of endotoxin in grain dust-induced lung disease.
AB  - To identify the role of endotoxin in grain dust-induced lung disease, we
      conducted a population-based, cross-sectional investigation among grain handlers
      and postal workers. The study subjects were selected by randomly sampling all
      grain facilities and post offices within 100 miles of Iowa City. Our study
      population consisted of 410 grain workers and 201 postal workers. Grain workers
      were found to be exposed to higher concentrations of airborne dust (p = 0.0001)
      and endotoxin (p = 0.0001) when compared with postal workers. Grain workers had a
      significantly higher prevalence of work-related (cough, phlegm, wheezing, chest
      tightness, and dyspnea) and chronic (usual cough or phlegm production)
      respiratory symptoms than postal workers. Moreover, after controlling for age,
      gender, and cigarette smoking status, work-related respiratory symptoms were
      strongly associated with the concentration of endotoxin in the bioaerosol in the
      work setting. The concentration of total dust in the bioaerosol was marginally
      related to these respiratory problems. After controlling for age, gender, and
      cigarette smoking status, grain workers were found to have reduced spirometric
      measures of airflow (FEV1, FEV1/FVC, and FEF25-75) and enhanced airway reactivity
      to inhaled histamine when compared with postal workers. Although the total dust
      concentration in the work environment appeared to have little effect on these
      measures of airflow obstruction, higher concentrations of endotoxin in the
      bioaerosol were associated with diminished measures of airflow and enhanced
      bronchial reactivity. Our results indicate that the concentration of endotoxin in
      the bioaerosol may be particularly important in the development of grain dust
      induced lung disease.

PMID- 7633716
TI  - Acute stress affects cytokines and nitric oxide production by alveolar
      macrophages differently.
AB  - The production of cytokines by alveolar macrophages was studied after exposure of
      rats to an acute stress paradigm (mild inescapable footshocks). When alveolar
      macrophages from nonstressed animals were isolated and cultured, they readily
      produced interleukin-1 beta (IL-1 beta), IL-6, and tumor necrosis factor-alpha
      (TNF-alpha) after stimulation with lipopolysaccharides (LPS). For these cytokines
      the dose response relationship for LPS was clearly biphasic. Nitric oxide (NO)
      production could only be detected upon LPS stimulation and seemed to be
      monophasic. However, when the animals were exposed to the acute stress paradigm,
      isolated alveolar macrophages (AM) showed a marked increase of IL-1 beta and TNF
      alpha secretion upon LPS stimulation in vitro, but no changes in the production
      of IL-6 were detected. In contrast, exposure to the stress paradigm resulted in a
      strong decrease in NO production. The results indicate that emotional stress can
      rapidly induce altered behavior of AM, which is discussed in view of the
      important role these cells play in the regulation of the local immune responses
      in the lungs and the possible contribution to asthma.

PMID- 7633715
TI  - Increase in activated CD8+ cells in bronchoalveolar lavage fluid in patients with
      diffuse panbronchiolitis.
AB  - To study the role of T cells in diffuse panbronchiolitis (DPB), we investigated T
      cell subsets in bronchoalveolar lavage fluid (BALF) or 33 patients with DPB, nine
      patients with bronchiectasis, and 20 healthy volunteers. BALF from DPB patients
      contained a higher percentage of neutrophils than that from patients with
      bronchiectasis or healthy volunteers, whereas the percentage of lymphocytes was
      similar in the three groups. DPB patients, however, had a higher number of
      lymphocytes and a reduced CD4/CD8 ratio compared with the other subjects. A two
      color analysis of T-cell subsets in peripheral blood and BALF revealed a
      significant increase in the percentage and number of CD8+HLA-DR+ cells and in the
      number of CD4+HLA-DR+ cells in BALF of DPB patients. The expression of the
      adhesion molecules CD 11a and CD18 on lung CD3+ cells was enhanced over that on
      blood CD3+ cells in DPB patients. However, there was no significant difference in
      the expression of these antigens in peripheral blood or BALF among the groups.
      There was no significant relationship between BALF interleukin (IL)-8 and
      lymphocyte accumulation in the lungs of the DPB patients, whereas a significant
      correlation between the percentage of neutrophils and IL-8 levels in BALF of DPB
      patients was observed. After treatment with macrolide antibiotics, a significant
      reduction in the number of lymphocytes and activated CD8+ cells and an elevation
      in the CD4/CD8 ratio in BALF of DPB patients was observed. Our findings suggest
      an activation of CD8+ cells in the airway lumen of DPB patients, supporting the
      hypothesis that lymphocytes are important cellular components of bronchial
      inflammation in DPB.

PMID- 7633717
TI  - Inhaled indomethacin prevents bronchoconstrictive response to distilled water but
      not to histamine in children with asthma.
AB  - We evaluated the effect of inhaled indomethacin, a nonsteroidal antiinflammatory
      drug (NSAID), against bronchoconstriction induced by ultrasonically nebulized
      distilled water (UNDW) in children with asthma. Ten children with asthma (eight
      males and two females, with a mean +/- SEM age of 10.7 +/- 0.7 yr), who had a
      decrease in FEV1 of at least 20% after UNDW inhalation, were enrolled in this
      study. These subjects were pretreated with inhaled indomethacin (3 mg/m2 body
      surface area) or placebo (0.9% saline) according to a single-blind, randomized,
      crossover design, and underwent a UNDW challenge test 15 min after the
      pretreatment. Furthermore, to study the possibility that indomethacin has a
      direct effect on airway smooth muscle, bronchial provocation with histamine was
      performed in seven subjects on two further days after pretreatment with
      indomethacin or placebo. Inhaled indomethacin had no effect on baseline pulmonary
      function, but did prevent the UNDW-induced decline in FEV1 (p < 0.01). Inhaled
      indomethacin did not modify the bronchoconstrictor response to histamine,
      indicating that a direct effect of this agent on airway smooth muscle is
      unlikely. The inhibition of local prostaglandin synthesis in the airways may be
      involved in the effect of indomethacin.

PMID- 7633718
TI  - Increased degranulation of eosinophil and neutrophil granulocytes in cystic
      fibrosis.
AB  - Increased serum and sputum concentrations of eosinophil cationic protein (ECP)
      and of neutrophil myeloperoxidase (MPO) have been described in patients with
      cystic fibrosis. Because numbers of eosinophils are normal in both peripheral
      blood and in the lung of patients with cystic fibrosis, we investigated whether
      eosinophils presented with an increased propensity to release their granule
      proteins. We investigated 20 patients with cystic fibrosis, 19 individuals with
      bronchial asthma, and 21 healthy nonatopic subjects. Isolated granulocytes were
      stimulated with serum-opsonized Sephadex G15 particles and the released amounts
      of ECP and MPO were measured by using radioimmunoassays. Eosinophils of patients
      with cystic fibrosis released significantly higher amounts of ECP than control
      subjects (p < 0.0001) and individuals with bronchial asthma (p < 0.0001). The
      release of MPO from neutrophils was also higher (p < 0.0001 and p < 0.005,
      respectively). Furthermore, a significant relationship between clinical variables
      and secretory activity of eosinophils was found in cystic fibrosis. We conclude
      that eosinophils as well as neutrophils obtained from patients with cystic
      fibrosis have an increased propensity to release their granule proteins which may
      be due to priming mechanisms. These findings would support anti-inflammatory
      treatment modalities in cystic fibrosis.

PMID- 7633719
TI  - Identification of allergic bronchopulmonary aspergillosis in cystic fibrosis
      patients by recombinant Aspergillus fumigatus I/a-specific serology.
AB  - Before specific therapy, such as oral corticosteroids, can be commenced it is
      essential to distinguish full-blown allergic bronchopulmonary aspergillosis
      (ABPA) from allergy to A. fumigatus in patients with cystic fibrosis (CF). For
      this purpose we have evaluated the diagnostic value of recombinant A. fumigatus
      allergen I/a (rAsp f I/a)-specific serology in 55 patients with CF. Based on
      clinical presentation and laboratory data, 10 CF patients had ABPA, 27 had
      Aspergillus allergy, and 18 were not allergic to A. fumigatus (CF control group).
      The serologic assays revealed a 10-fold increase in rAsp fI/a-specific IgE, a 5
      fold increase in rAsp fI/a-specific IgG1, and a 4-fold increase in rAsp fI/a
      specific IgG4 antibodies in ABPA patients compared with the Aspergillus allergy
      and CF control groups. Sera from 11 CF patients were analyzed without knowledge
      of their clinical state or diagnosis of ABPA. All ABPA patients (4 of 11) were
      accurately identified. We conclude that rAsp fI/a-specific serology is a highly
      sensitive and specific test that can be used to identify ABPA reliably in CF
      patients.

PMID- 7633720
TI  - Decreased alveolarization in baboon survivors with bronchopulmonary dysplasia.
AB  - In this study, 12 male baboons were delivered by hysterotomy at 75% of gestation.
      The development of a nonlethal baboon model permitted a study of lung growth and
      development in long-term survivors. Control animals were ventilated with
      clinically appropriate oxygen for the 21 d study period. BPD animals were
      ventilated with PPV and an FIO2 of 1.0 for 7 d, followed by an FIO2 of 0.8 for 14
      d. They survived for 33 wk, at which time a right lower lobe lobectomy was
      performed. Controls showed normal well-alveolated lungs, whereas BPD lungs showed
      enlarged airspaces focally, nonclassifiable as alveoli, alveolar ducts, or
      respiratory bronchioles. Volume densities of alveoli were decreased significantly
      (p = 0.0009), and enlarged airspaces were significantly increased (p = 0.0003) in
      the BPD group compared with controls. Alveolar counts verified a significant
      decrease in alveoli (p = 0.004), and the internal surface area was significantly
      decreased (p = 0.05) in BPD treated animals compared with controls. These data
      document that a mild to moderate BPD lesion results in a significant and
      permanent loss of alveoli and a significant increase in enlarged, unclassifiable
      airspaces, which together result in a decreased total internal surface area in
      baboons that survive with their disease.

PMID- 7633721
TI  - Muscle energy metabolism and nutritional status in patients with chronic
      obstructive pulmonary disease. A 31P magnetic resonance study.
AB  - We investigated the relationship between nutritional status and muscle energy
      metabolism during exercise in 18 male patients with chronic obstructive pulmonary
      disease (COPD) and 15 male control subjects using 31P nuclear magnetic resonance
      spectroscopy (31P-MRS). The patients and control subjects were further
      categorized as in either a well-nourished (% ideal body weight, % IBW > or = 90)
      or malnourished (% IBW < 90) state. Muscle energy metabolism was evaluated by
      determining the ratios PCr/(PCr + Pi) (PCr, phosphocreatine; Pi, inorganic
      phosphate), and ATP/(PCr + Pi + ATP). The exercise consisted of repetitive hand
      grips performed against a load. The work rate was normalized for the individual's
      lean muscle mass by dividing work performed by the forearm fat-free cross
      sectional area, which was calculated using 1H-MRS. The PCr/(PCr + Pi) values
      during exercise did not correlate with the % IBW in any of the groups of control
      subjects or COPD patients. Furthermore, the PCr/(PCr + Pi) did not correlate with
      the normalized work rate in either the well-nourished or malnourished subject
      groups. However, there were correlations within the groups of control subjects
      and COPD patients. The PCr/(PCr + Pi) values for the normalized work rate were
      consistently lower in the COPD patients than in the control subjects. These
      findings suggest that the altered muscle metabolism in COPD patients is not
      affected by their nutritional status.

PMID- 7633723
TI  - Reference values of pulmonary diffusing capacity during exercise by a rebreathing
      technique.
AB  - Normal reference values of the pulmonary diffusing capacity for carbon monoxide
      (DLCO), diffusing capacity of the membrane (DMCO), and pulmonary capillary blood
      volume (VC) were derived by a rebreathing technique in 44 normal, healthy,
      nonsmoking individuals ranging from 17 to 68 yr of age. Simultaneous measurements
      of DLCO, lung volumes, pulmonary blood flow, and septal tissue volume were
      determined at rest and during steady-state exercise of 25, 50, and 80% of maximal
      workload and at two levels of alveolar O2 tension. DMCO and VC were calculated
      using the Roughton-Forster relationship. Using stepwise regression analysis, DLCO
      and DMCO (in ml CO/min/mm Hg) were found to be significantly related to pulmonary
      blood flow (Qc in L/min), age (in years), and body surface area (BSA in square
      meters). VC (in ml) was found to be significantly related to QC and BSA.
      Normalization of measured data with respect to these variables largely eliminated
      male versus female differences. We conclude that QC is the most important
      determinant of the recruitment of diffusing capacity. From rest to near-maximal
      exercise, DLCO, DMCO, and VC increase linearly with respect to QC without
      evidence of reaching a plateau.

PMID- 7633722
TI  - Comparison of computed density and macroscopic morphometry in pulmonary
      emphysema.
AB  - High-resolution computed tomography (HRCT) scans were obtained at 1 cm intervals
      in 63 subjects referred for surgical resection of a cancer or for transplantation
      to find out whether the relative area of lung occupied by attenuation values
      lower than a threshold would be a measurement of macroscopic emphysema. Using a
      semiautomatic procedure, the relative areas occupied by attenuation values lower
      than eight thresholds ranging from -900 to -970 HU were calculated on the set of
      scans obtained through the lobe or the lung to be resected. The extent of
      emphysema was quantified by a computer-assisted method on horizontal paper
      mounted lung sections obtained every 1 to 2 cm. The only level for which no
      statistically significant difference was found between the HRCT and the
      morphometric data was -950 HU. To determine the number of scans sufficient for an
      accurate quantification, we recalculated the relative area occupied by
      attenuation values lower than -950 HU on progressively fewer numbers of scans and
      investigated the departure from the results obtained with 1 cm intervals. Because
      of wide variations in this departure from patient to patient, a standard cannot
      be recommended as the optimal distance between scans.

PMID- 7633725
TI  - Comparison of diaphragm strength between healthy adult elderly and young men.
AB  - To test the hypothesis that aging is associated with a reduction in the
      diaphragm's force-generating capacity, we compared the maximum transdiaphragmatic
      pressure (Pdimax) obtained during voluntary maximal inspiratory efforts in nine
      young (19-28 yr) and ten elderly (65-75 yr) subjects. The relationship between
      Pdi and lung volume was compared in the two groups by having subjects make
      maximal inspiratory maneuvers at specified lung volumes (i.e., 20, 40, and 80%
      vital capacity). Subjects underwent symptom-limited exercise tests to
      characterize their aerobic capacities and evaluate the relationship between
      aerobic capacity and Pdimax. The average Pdimax of the elderly subjects (128 +/-
      9 cm H2O) was significantly lower (p < 0.003) than the average Pdimax of the
      younger subjects (171 +/- 8 cm H2O). In the elderly, Pdi was lower across the
      range of lung volumes tested (p < 0.001), and Pdimax occurred at similar relative
      lung volumes (elderly, at 47% total lung capacity [TLC]; young, at 50% TLC) in
      both groups. The elderly subjects were quite fit based on their VO2max, and there
      was no significant relationship between Pdimax and VO2max. This study suggests
      that diaphragm strength is reduced in elderly individuals. This age-related
      decrease in diaphragm strength may predispose elderly patients to diaphragm
      fatigue in the presence of conditions that impair inspiratory muscle function or
      increase ventilatory load.

PMID- 7633724
TI  - Effect of chronic resistive loading on ventilatory control in a rat model.
AB  - Acute resistive loading of the airway has been shown to activate the endogenous
      opioid system, with subsequent depression of ventilation. The present
      investigation was designed to assess the effect of chronic airway loading on
      ventilation and CO2 sensitivity, and to determine whether the endogenous opioid
      system contributes to long-term modulation of ventilatory control in this
      setting. A flow-resistive ventilatory load was imposed in 2-mo-old rats by
      surgical implantation of a circumferential tracheal band that approximately
      tripled tracheal resistance. Respiration and CO2 sensitivity were serially and
      noninvasively assessed by barometric plethysmography over a period of 21 wk.
      Ventilatory output was assessed as minute inspiratory effort, which was defined
      as the product of plethysmograph signal amplitude, inspiratory time, and
      respiratory rate (RR). CO2 sensitivity was calculated as the percent change in
      minute inspiratory effort from room air to CO2 exposure. The effect of naloxone
      administration on these parameters was also determine. Arterial blood gases
      demonstrated hypercapnia with maintenance of normoxia in loaded rats; these
      findings persisted for the duration of the study. Two days after surgery, rats
      with tracheal obstruction demonstrated a lower RR than controls during room air
      breathing and during CO2 stimulation. CO2 sensitivity was significantly depressed
      in obstructed animals at this time. Escape from suppression of RR and CO2
      sensitivity was evident by 14 to 21 d after obstruction; however, suppression of
      these parameters reappeared and was maintained from 56 to 147 d after
      obstruction. Naloxone augmented minute inspiratory effort during CO2 stimulation
      at 2 d after obstruction but not thereafter; naloxone had no effect in control
      rats. These data indicate that chronic airway loading suppresses RR and CO2
      sensitivity in a triphasic manner. The early suppression is partially reversible
      by naloxone; late-appearing suppression is unaffected by naloxone and is
      presumably mediated by mechanisms that do not involve endogenous opioids.

PMID- 7633726
TI  - Role of nitric oxide in endotoxin-induced metabolic and vascular dysregulation of
      the canine diaphragm.
AB  - We assessed the role of nitric oxide (NO) in the regulation of diaphragmatic O2
      uptake (Vo2di) and phrenic vascular resistance during endotoxemia in
      anesthetized, mechanically ventilated dogs. Left diaphragmatic vasculature was
      isolated and briefly pump perfused with arterial blood at a normal flow rate, at
      a high rate (50% higher than normal), and at low rat (60 to 70% lower than
      normal). At each rate, Vo2di and phrenic perfusion pressure (Pphr) were measured.
      Escherichia coli endotoxin (100 mg) was infused intravenously over 90 min in
      several groups of animals, whereas normal saline was infused into the other.
      Endotoxin infusion increased Vo2di and reduced Pphr at a given flow rate. These
      parameters remained unchanged in the saline-infused animals. Infusion of NG-nitro
      L-arginine methyl ester (LNAME 6 x 10(-4) M) into the phrenic artery of the
      endotoxin group reversed the decline in Pphr with no effect on Vo2di. LNAME
      infusion in the saline group increased Pphr at normal and high flow rates only.
      Single intravenous injections of LNAME increased arterial pressure and reduced
      cardiac output in endotoxemic animals, whereas only an increase in arterial
      pressure was observed in saline-infused animals. Serum arterial and phrenic
      venous NO concentrations measured in separate groups of animals increased
      significantly after endotoxin infusion, whereas saline infusion had no effect on
      these parameters. These results indicate that enhanced NO release plays a
      significant role in endotoxin-induced phrenic and systemic vasodilation. However,
      the increase in Vo2di in the endotoxin group does not seem to be mediated by NO
      release.

PMID- 7633727
TI  - Abnormalities of pulmonary function tests after marrow transplantation predict
      nonrelapse mortality.
AB  - To determine whether pulmonary function test (PFT) results after marrow
      transplantation were predictive of nonrelapse mortality, a review was made of
      prospective, nonrandomized PFT results for association with nonrelapse mortality
      by log-rank test and Cox proportional hazards modeling. The setting was a
      tertiary referral center. The patients were all marrow recipients who performed
      PFT between Days 60 and 120 after marrow transplantation between July 1, 1983 and
      December 31, 1990 (n = 906). At 3 mo after transplantation, the mean values for
      total lung capacity (TLC) and diffusing capacity decreased, and restrictive
      ventilatory defects (TLC < 80% of predicted) were noted in 34% of the cohort.
      Airflow rates (FEV1/FVC) were unchanged. A restrictive lung defect at 3 mo after
      transplant or a significant decline (> or = 15%) in TLC from baseline despite
      remaining within the normal range was associated with a twofold increased risk of
      nonrelapse mortality. Neither airflow obstruction nor impairment in diffusing
      capacity was associated with an increased risk. Abnormalities of the TLC at 3 mo
      after transplant were associated with death with respiratory failure, but not
      with an increased risk of chronic graft-versus-host disease (GVHD). There is an
      increase in the nonrelapse mortality rate associated with either the presence of
      a restrictive defect 3 mo after marrow transplantation or a significant decline
      in lung volume compared with baseline. This effect is most pronounced more than 1
      yr after marrow transplant and appears to be a result of an increase in the rate
      of death with respiratory failure, not chronic GVHD.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7633728
TI  - Standard flow-time waveforms for testing of PEF meters.
AB  - The American Thoracic Society (ATS) has recommended the use of 24 volume-time
      waveforms for the testing of spirometers. Although these waveforms include values
      of peak expiratory flow (PEF), they were not originally intended to test PEF
      meters, but, rather, volume parameters for spirometers. In addition, the practice
      of using ATS volume-time Waveform 24 with varying multiplying factors does not
      provide the range of flow-time waveform shapes (rise times) needed to evaluate
      PEF meters. Accordingly, we have developed a set of 26 flow-time waveforms
      specifically selected to evaluate PEF meters. PEF and other flow parameters (rise
      time and time to PEF) can be directly measured from these flow-time waveforms.
      When PEF determined directly from the flow-time curve was compared with PEF
      determined indirectly from a volume-time curve (ATS-recommended algorithm with an
      80 ms time segment), as much as a 10.7% difference between the two methods was
      observed using a waveform with a fast rise time. In contrast, there was very
      little difference between the various methods of deriving PEF for waveforms with
      slower rise times. These 26 flow-time waveforms provide a means of defining PEF
      for the testing of software algorithms and the testing of PEF meters with
      computer-driven mechanical pumps.

PMID- 7633729
TI  - Frequency response of portable PEF meters.
AB  - Peak expiratory flow (PEF) is a dynamic parameter and therefore requires a
      measuring device with a high-frequency response. This study evaluated the
      frequency-response characteristics of eight commercially available PEF meters,
      using simulated forced-expiratory maneuvers with a computer-controlled mechanical
      pump. Three different PEF levels were used (200, 400, and 600 L/min) at six
      levels of harmonic-frequency content similar to those observed in human subjects.
      For waveforms with higher frequency content (at the high end or above the
      physiologic range), the Assess, Vitalograph, Pocket Peak, and Spir-O-Flow PEF
      meters all overread PEF (greater than 15% difference from target values) at all
      three PEF levels. These results suggest that the frequency response of PEF meters
      is an important consideration in the selection of such meters and should be
      included in device requirements. The current practice of using various levels of
      American Thoracic Society (ATS) waveform 24 with its low-frequency content may
      not adequately evaluate the frequency characteristics of PEF meters. An upper
      range (5% of the fundamental frequency) of 12 Hz, within the range observed in
      normal subjects, appears to be more practical than an upper limit of 20 Hz.

PMID- 7633730
TI  - A community study of snoring and sleep-disordered breathing. Symptoms.
AB  - Four hundred forty-one subjects 34 to 69 yr of age were recruited from a random
      sample of the community. The sample was biased in favor of men, snorers, and
      subjects with subjective sleep complaints. They answered a questionnaire and were
      monitored in their homes for sleep-disordered breathing (SDB). This report
      concerns the presence of symptoms associated with the obstructive sleep apnea
      (OSA) syndrome in the subjects with SDB detected in this community sample. Most
      of the symptoms commonly recognized as occurring in OSA were associated with SDB
      in our sample: snoring that disturbed the sleep of other persons, reports of
      apnea, reports of gasping or choking sounds during sleep, and finding the
      bedclothes in disarray in the mornings had significant univariate associations
      with SDB. Nocturnal choking and morning headache were negatively associated with
      SDB. Excessive daytime somnolence (EDS) was reported by 41% of those with SDB,
      but it was also reported by 37% of snorers without SDB and by 37% of nonsnorers.
      We conclude that the symptoms seen in clinic patients with OSA also occur in
      subjects with SDB who have not presented for medical attention. Enumeration of
      these symptoms by questionnaire, however, is a poor test for OSA in the
      community. EDS was reported by a higher than expected proportion of subjects not
      affected by SDB, suggesting that causes of self-reported EDS other than SDB may
      be common.

PMID- 7633731
TI  - A community study of snoring and sleep-disordered breathing. Prevalence.
AB  - We conducted a study of the prevalence of sleep-disordered breathing in subjects
      derived from a random sample of the population. A total of 2,202 subjects 35 to
      69 yr of age were approached. Four hundred forty-one answered a questionnaire
      concerning their sleep symptoms, general health, and habits such as alcohol
      consumption, and they were monitored for sleep-disordered breathing (SDB). The
      sample was biased in favor of snorers and those with other subjective sleep
      complaints. Fifty-six percent of the subjects were men. Of the 441 subjects 79
      (17.9%) had SDB (more than 15 episodes of apnea or hypopnea per hour: respiratory
      distress index [RDI] > or = 15), 289 were snorers but had RDI < 15, and 73 were
      nonsnorers. The prevalence of SDB in this sample was therefore at least 3.6% (79
      of 2,204). The minimum prevalence in men was 5.7%, and in women it was 1.2%.
      Logistic regression identified only male sex as an independent predictor of
      snoring without SDB (adjusted odds ratio [OR], 3.24; 95% CI, 1.33 to 7.82), body
      mass index (adjusted OR for an increase of 5 kg/m2, 0.95; 95% CI, 0.85 to 1.05),
      and alcohol consumption (adjusted OR for an increase of 10 g/day, 1.05; 95% CI,
      0.84 to 1.37) were not significant predictors of snoring. The independent
      predictors of SDB among snorers were age (adjusted OR for an increase of 5 yr,
      1.26; 95% CI, 1.08 to 1.47) and neck circumference (adjusted OR for an increase
      of 2 cm, 1.53; 95% CI, 1.16 to 2.00).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7633732
TI  - A community study of snoring and sleep-disordered breathing. Health outcomes.
AB  - Four hundred forty-one subjects 34 to 69 yr of age were recruited from a random
      sample of the community. They answered a questionnaire and were monitored in
      their homes for sleep-disordered breathing (SDB). This report concerns the
      association between observed SDB and arterial hypertension and vascular disease.
      Hypertension was defined as self-report of a diagnosis of hypertension made by a
      physician, current treatment for hypertension, or a systolic pressure greater
      than 150 mm Hg or a diastolic pressure greater than 90 mm Hg. Coronary artery
      disease was defined by self-report of angina or myocardial infarction of "heart
      attack." There were few cases of stroke or claudication, and a category of
      "occlusive vascular disease" was defined by self-report of coronary artery
      disease or of "blocked arteries" or stroke. Subjects were classified as snorers
      (n = 289) or nonsnorers (n = 73) by self-report of regular snoring, and as having
      SDB (n = 79) if more than 15 abnormal respiratory events were recorded per hour
      of recording. There were significant increases in the prevalence of hypertension,
      coronary artery disease, and occlusive vascular disease from nonsnorers (26, 7,
      and 10%, respectively) through snorers (39, 12, and 17%) to subjects with SDB
      (57, 20, and 28%). The crude odds ratio for SDB versus nonsnorers was 3.8 (95%
      CI, 1.9 to 7.5) for hypertension, 3.5 (1.2 to 10.0) for coronary artery disease,
      and 3.7 (1.5 to 9.1) for occlusive vascular disease.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7633733
TI  - The effect of posture on airway caliber with the sleep-apnea/hypopnea syndrome.
AB  - Snoring and sleep apnea are more common in the supine than seated position. We
      therefore studied the effect of posture on upper-airway caliber in normal
      subjects, snorers, and subjects with the sleep-apnea/hypopnea syndrome (SAHS). We
      measured upper-airway cross-sectional area by acoustic reflection in 110 SAHS
      patients (apnea/hypopnea index [AHI] > 15), 70 snorers without SAHS (AHI < 15),
      and 40 male controls matched for body-mass index (BMI) to the 40 SAHS patients.
      SAHS patients in the seated position had smaller upper-airway areas at the
      orophyngeal junction (OPJ) than either the snorers (p < 0.01) or the normal
      subjects (p < 0.02), but there were no differences between groups in airway cross
      sectional areas in the supine or lateral recumbent positions. SAHS patients had
      significantly smaller decreases in OPJ area from the seated to either the supine
      (p < 0.001) or lateral recumbent (p < 0.001) positions than did the snorers. SAHS
      patients also had smaller (p < 0.05) decreases in OPJ area upon lying down than
      did the BMI-matched normal subjects. These data are compatible with SAHS patients
      defending their upper airway more upon lying down than do snorers or normal
      subjects.

PMID- 7633734
TI  - Influence of gender on waking genioglossal electromyogram and upper airway
      resistance.
AB  - Obstructive sleep apnea is generally recognized as more common in men than in
      women. This could relate to gender differences in either ventilatory control
      mechanisms or the structure and function of the pharyngeal airway. Most studies
      suggest that women have a structurally smaller pharyngeal airway than men, which
      would likely predispose rather than protect them from airway collapse. However,
      pharyngeal airway patency is actually a dynamic interaction between anatomy and
      pharyngeal muscle activity. We therefore hypothesized that females may have
      increased pharyngeal dilator muscle activity, thereby protecting them from airway
      collapse during sleep. To test this hypothesis, we compared genioglossal EMG (GG
      EMG, measured as a percentage of maximal muscle activity) and upper airway
      resistance in 22 healthy subjects, 11 males and 11 females, during wakefulness.
      No significant difference in pharyngeal resistance could be found between the
      genders. However, inspiratory peak phasic and expiratory tonic GG-EMG activity
      were both significantly greater in females (GG-EMG peak phasic; 24.3 +/- 3.8
      versus 13.1 +/- 4.5% of maximum, p < 0.02; GG-EMG tonic; 12.2 +/- 2.8 versus 4.7
      +/- 1.2% of maximum, p < 0.01). In addition, females demonstrated a significant
      EMG response to inspiratory loading that was not observed in men. We conclude
      that women have, under basal conditions during wakefulness, augmented
      genioglossal muscle activity compared with men. To the extent that this augmented
      muscle activity is maintained across states, the female airway may be more stable
      and less collapsible.

PMID- 7633735
TI  - Active expiratory glottic closure during permeability pulmonary edema in
      nonsedated lambs.
AB  - It has long been claimed that the active expiratory glottic closure observed in
      newborns, especially during hyaline membrane disease, is related to hypoxia.
      However, we recently showed that hypoxia does not lead to active expiratory
      glottic closure in nonsedated lambs. In this study, we test the hypothesis that
      glottic closure is related to an excess of lung water present at birth. We
      studied 17 nonsedated lambs after inducing a permeability pulmonary edema via
      intravenous of either oleic acid (8 lambs) or halothane (9 lambs). We recorded
      airflow via a facial mask and pneumotachograph, as well as the electromyographic
      activity (EMG) of the thyroarytenoid muscle (TA), a glottic adductor. Blood gases
      were measured in 8 lambs via a brachial artery catheter. We identified laryngeal
      expiratory airflow braking on the breath-by-breath computed flow-volume loop and
      TA expiratory EMG as evidence of active expiratory glottic adduction. After the
      injection of oleic acid or halothane, an active expiratory glottic closure was
      recorded in all lambs but 1, usually throughout the recording period (60 to 300
      min). The active expiratory glottic closure was not inhibited after correction of
      the hypoxia. We conclude that, in nonsedated lambs, a permeability pulmonary
      edema induces an active expiratory glottic closure. We hypothesize that the
      expiratory glottic closure commonly observed in newborns could help to ameliorate
      the alveolocapillary gas exchange by reopening the flooded alveoli.

PMID- 7633736
TI  - Pulmonary function tests in HIV-infected patients without AIDS. Pulmonary
      Complications of HIV Infection Study Group.
AB  - To determine the prevalence, incidence, and types of lung diseases that occur in
      association with HIV infection, 1,353 subjects, including HIV-seropositive
      homosexual men, injection drug users, female sexual partners of HIV-positive men,
      and HIV-seronegative control subjects from the first two transmission categories
      were evaluated prospectively in a multicenter study. Patients with AIDS at the
      time of initial evaluation were excluded. One thousand two-hundred ninety-four
      subjects who had no AIDS-defining diagnosis within 3 mo of enrollment had
      measurements of FVC, FEV1 and DLCO at the time of enrollment. As a group, all
      subjects had mean values of FVC and FEV1 close to 100% predicted. Those with CD4
      counts below 200/mm3 had slightly reduced DLCO compared with the others. Subjects
      with a history of HIV-associated symptoms (thrush, weight loss, herpes zoster)
      also had a reduced DLCO compared with those without symptoms. Injection drug
      users had reduced FVC, FEV1 and DLCO compared with homosexual men and female
      sexual partners of HIV-infected men, with DLCO more substantially reduced. Part
      of the reduction in DLCO in drug users was attributable to factors other than HIV
      infection, especially cigarette smoking and race. Using predicted values that
      take cigarette smoking into account, the prevalence of abnormality in DLCO was
      higher among injection drug users (33.3%) than among homosexual men (11.2%) and
      female sexual partners (12.7%). These results show that advanced HIV infection,
      characterized by CD4 count < 200/mm3 or HIV-associated symptoms, and factors
      unrelated to HIV infection, including race, cigarette smoking, and injection drug
      use, are all associated with reductions in DLCO measurements.

PMID- 7633737
TI  - Protein 1 (Clara cell protein) serum levels in healthy subjects and patients with
      bacterial pneumonia.
AB  - Serum levels of protein 1 (P1), a Clara cell secretory protein, were studied in
      942 healthy subjects in relation to sex, age, and smoking habits and in 117
      patients with bacterial pneumonia in relation to prognosis. P1 values in
      bacterial pneumonia patients at disease onset were compared with those in 234
      healthy control subjects matched by sex and age. P1 values in healthy males were
      highest in those 30 to 39 yr of age and highest in healthy females > or = 70 yr
      of age but lowest in those 30 to 49 yr of age. P1 values in healthy males were
      significantly higher than those in females in the 30- to 39-yr age group (p <
      0.05). Male smokers showed higher P1 values than nonsmokers, but without a
      significant difference. P1 values in patients with pneumonia were significantly
      lower than in control subjects (p < 0.0001). P1 values were significantly lower
      in patients treated with a respirator than in in patients treated without a
      respirator (p < 0.05). In 59 patients, whose P1 values could be followed up until
      the outcome of pneumonia, all 37 recovered patients showed significantly
      increased P1 values after recovery (p < 0.001), and all 22 who died of their
      illness showed significantly decreased P1 values just before death (p < 0.01). We
      thus conclude that P1 serum levels were significantly affected by sex and by the
      degree of seriousness in bacterial pneumonia.

PMID- 7633738
TI  - Surfactant protein A predicts survival in idiopathic pulmonary fibrosis.
AB  - The purpose of this study was to determine if the measurement of surfactant
      protein A (SP-A) in bronchoalveolar lavage (BAL) fluid predicts survival in
      patients with idiopathic pulmonary fibrosis (IPF). We performed BAL on 44
      patients with IPF and 33 healthy volunteers. SP-A and total phospholipid (PL)
      were measured in the surfactant pelleted by centrifugation and expressed as a
      ratio to account for differences in the alveolar surface area sampled. The mean
      SP-A/PL was lower in patients with IPF than in healthy volunteers (31.8 +/- 2.8
      versus 63.9 +/- 6.4 micrograms/mumol, p = 0.006) and in patients who died within
      2 yr than in those who survived (23.4 +/- 2.6 versus 37.5 +/- 4.2
      micrograms/mumol, p = 0.015). Using Cox's proportional hazard model, we found
      that SP-A/PL modeled continuously was associated with survival time (p = 0.002).
      The 5-yr survival of patients with SP-A/PL above the median level for all
      patients with IPF (29.7 micrograms/mumol) was more than twice that of patients
      below the median (68 versus 30%, p = 0.007). SP-A/PL improved upon prediction of
      survival modeled by most routine physiologic variables with the exception of
      percent predicted TLC or the multifarious clinical-radiographic-physiologic score
      (CRP). Cellular analysis of lavage did not predict survival in this cohort of
      patients. We conclude that SP-A/PL is a biochemical marker in lavage that
      predicts survival in patients with IPF.

PMID- 7633741
TI  - Diagnosis of obstructive sleep apnea using a portable transducer catheter.
AB  - As an initial step in simplifying the diagnosis of sleep apnea with a view toward
      using portable equipment in the home setting, we examined the efficacy of a
      portable transducer catheter that measures intrathoracic pressure. This catheter,
      connected to a miniature data-logger, can be introduced nasally into the airway,
      and the data so collected can be acquired, stored, and analyzed off-line. We
      tested this catheter against standard nocturnal polysomnography in 10 patients
      suffering from obstructive sleep apnea. We found that by using a combination of
      the raw pressure signal and an envelope pressure signal, we accurately identified
      apneas and hypopneas, and classified them as obstructive, central, and mixed. For
      the 10 subjects studied, the polysomnographic apnea/hypopnea index was 34 + 30,
      versus 32 + 28 obtained by analysis of the pressure tracings. Analysis of 200
      respiratory events identified one-by-one from polysomnograms and pressure
      tracings revealed close correspondence between the two methods. The average
      duration of apneas was 22.1 + 6.7 s as measured by polysomnography, versus 21.9 +
      6.6 s as measured from pressure tracings. Furthermore, there was excellent
      agreement between the two methods (kappa = 0.89, 95% confidence limits = 0.84 to
      0.94). We conclude that our technique for identifying apnea based on measurements
      of intrathoracic pressure using a thin, portable transducer catheter is a
      promising method for simplifying the diagnosis of this disorder.

PMID- 7633739
TI  - Carboxypeptidase M activity is increased in bronchoalveolar lavage in human lung
      disease.
AB  - Carboxypeptidase M (CPM) cleaves the C-terminal arginine and lysine of peptides;
      it is expressed in the lung, especially on the plasma membrane of alveolar type I
      cells. Here, we report on CPM in human bronchoalveolar lavage (BAL) collected
      from 69 patients and analyzed for activity, cell number and type, and protein
      level. Seventy-six percent of CPM activity, measured at pH 7.5 with 5
      dimethylamino-naphthalene-1-sulfonyl-alanyl-arginine (Dansyl-Ala-Arg) substrate,
      was immunoprecipitated with polyclonal antibody to purified human enzyme. In
      patients without active lung disease, CPM activity in BAL was 7.69 (+/- 2.12)
      nmol/h/mg protein, but in patients with acute pneumonia, it was 29.25 (+/- 4.06)
      (p < 0.01). In patients with Pneumocystis carinii pneumonia, CPM activity was
      elevated to 26.00 (+/- 4.85) (p < 0.01) and in patients with lung cancer, to
      30.95 (+/- 4.12) (p < 0.01). The activity was not associated with the cellular
      elements of BAL. The highest specific activity was in the large aggregate
      fraction of surfactant, which also contained the highest concentration of
      phosphorus. Transmission electron microscopy of this fraction revealed the
      presence of typical lamellar bodies and tubular myelin structures. The high CPM
      activity may stem from its induction and release in acute lung disease. In
      addition, CPM may be a marker of infection with certain pathogens and an
      indicator of type I cell injury in parenchymal lung diseases.

PMID- 7633742
TI  - Obstructive sleep apnea: the use of nasal CPAP in 80 children.
AB  - This is a retrospective review of children 15 years of age or younger, who
      underwent overnight sleep studies between 1980 and 1993. All were diagnosed and
      treated for obstructive sleep apnea (OSA). Overnight studies were performed for
      OSA in 413 children. One hundred seventy-five (42.4%) children were treated with
      adenotonsillectomy and 80 (19.4%) with nasal mask continuous positive airway
      pressure (nCPAP). The proportion of male children was greater than expected in
      both the entire study group (69%, p < 0.001) and in those treated with nCPAP for
      OSA (71% p < 0.001). There was no significant difference between the mean age of
      the children treated with nCPAP (5.7 +/- 0.5 yr) and the entire group studied
      (5.04 +/- 0.21 yr). A greater proportion of the children who received nCPAP
      therapy had a congenital syndrome or malformation than in the group with OSA as a
      whole; 27.7% of children assessed for OSA were affected, and 53% of those
      children with OSA who received treatment with nCPAP (p < 0.001). Therapy with
      nCPAP (mean duration 15 +/- 3 mo, mean pressure 7.9 cm H2O) eliminated the signs
      of OSA in 72 children (90%). Respiratory disturbance index fell from a mean of
      27.3 +/- 20.2 to 2.55 +/- 2.74 (p < 0.001). Eight of 32 children who underwent
      pressure determination studies could not tolerate nCPAP above an upper limit
      because of hypoventilation or frequent central apneas. Nevertheless, we conclude
      that nCPAP is an effective and generally well-tolerated therapy for treatment of
      OSA in infants and children.

PMID- 7633744
TI  - Radiographic abnormalities in tuberculosis and risk of coexisting human
      immunodeficiency virus infection. Methods and preliminary results from Bujumbura,
      Burundi.
AB  - We evaluated the age profile and chest radiographic abnormalities in 158 patients
      from Bujumbura, Burundi, with new-onset intrathoracic tuberculosis (pulmonary,
      pleural, or hilar/mediastinal adenopathy), to identify features that were
      associated with and would allow prediction of HIV seropositivity or
      seronegativity. Using agreed-upon criteria and prepared reporting forms, initial
      chest radiographs were reviewed by three readers, first independently and then at
      a consensus conference. Of the 158 patients, 105 (66%) were HIV seropositive and
      53 patients were seronegative. Seropositive subjects (mean age, 35.8 yr) were
      older (p = 0.001) than seronegative subjects (mean age, 29.4 yr). Significant or
      borderline differences between HIV-seropositive and -seronegative patients
      included the frequency of small nodular lesions (p = 0.03), upper lobe cavitation
      (p = 0.05), and lymphadenopathy (p = 0.12), and the location of parenchymal
      abnormalities (p = 0.0006). Stepwise logistic regression revealed four important
      variables: age, small lesions, location, and lymphadenopathy; these were then
      used to derive an equation to calculate the probability that a given tuberculosis
      patient was HIV seropositive. Our mathematical model fit the observed data and
      the equation predicted serologic findings reasonably well. We conclude that it is
      possible to determine with useful probability a Burundian tuberculosis patient's
      HIV serologic status.

PMID- 7633743
TI  - Radiographic abnormalities in tuberculosis and risk of coexisting human
      immunodeficiency virus infection. Results from Dar-es-Salaam, Tanzania, and
      scoring system.
AB  - First, we evaluated the age profile and chest radiographic abnormalities in 146
      patients from Dar-es-Salaam, Tanzania, with new-onset intrathoracic tuberculosis
      (pulmonary, pleural, or hilar/mediastinal adenopathy), to identify features that
      were associated with human immunodeficiency virus (HIV) seropositivity or
      seronegativity; then, we combined these data with those from a companion
      investigation in Burundi to develop a simple scoring system to predict HIV
      serologic status. Using agreed-upon criteria and simplified reporting forms,
      initial chest radiographs were reviewed by three readers, first independently and
      then at a consensus conference. Of the 146 patients, 80 (55%) were HIV
      seropositive and 66 were seronegative. More seropositive than seronegative
      subjects were 31 to 40 yr old (p = 0.03). Because the radiographic
      characteristics of the two serologic groups were similar in Tanzania and Burundi,
      we combined the data for stepwise logistic regression that revealed four highly
      significant variables: age, small lesions, location, and lymphadenopathy. From
      these, we obtained an equation to calculate the probability that a given
      tuberculosis patients was HIV seropositive and then we derived a scoring system
      that in its simplest form (threshold) predicted serologic status correctly in
      68.1% of patients; a graded scale was even more accurate in the high (89.1%) and
      low (82.6%) ranges. This scoring system should be useful when serologic testing
      is unavailable or refused.

PMID- 7633745
TI  - Expired nitric oxide levels during treatment of acute asthma.
AB  - Nitric oxide (NO) is known to be present in measurable quantities in the exhaled
      air of normal subjects and at higher concentrations in asthmatic subjects not
      treated with glucocorticoids. We confirmed these findings by analyzing the mean
      mixed expired NO concentrations of 43 stable asthmatics and 90 normal subjects;
      NO levels were higher in the asthmatic population (13.9 parts per billion [ppb]
      versus 6.2 ppb, p < 0.001). Although the effects of glucocorticoids on the NO
      content of mixed expired air are known, it is not known if beginning systemic
      glucocorticoid therapy reduces exhaled NO levels in a given individual. To
      examine this question, seven patients needing emergency therapy for asthma
      underwent repeated measurements of mixed expired NO levels during their course of
      treatment with glucocorticoids. All patients had a reduction in mixed expired NO
      concentration (p = 0.002) and an accompanying improvement in airway obstruction.
      The decrease in exhaled NO was evident as early as 48 h after the initiation of
      therapy (p = 0.05). These data suggest mixed expired NO concentrations may prove
      useful as an index of asthma severity and treatment efficacy for an individual
      patient.

PMID- 7633746
TI  - Effect of preinspiratory maneuver on the single-breath DLCO.
AB  - We have observed in some patients with pulmonary disease and normal subjects that
      the difference between two successive measurements for single-breath DLCO
      amounted to 10%. By scrutinizing data from these subjects, we observed that they
      spontaneously changed their preinspiratory maneuver just before inhaling the test
      gas mixture. The purpose of the present work is to assess the influence of five
      different preinspiratory maneuvers on DLCO. Nine healthy males were investigated.
      They performed at random the five following maneuvers: (A) rapid exhalation from
      functional residual capacity (FRC) to residual volume (RV), (B) rapid exhalation
      from FRC to RV and long apnea at RV, (C) rapid exhalation from FRC to RV and
      short apnea at RV, (D) slow exhalation at a constant speed from FRC to RV, and
      (E) curvilinear exhalation from FRC to RV. The DLCO values after maneuver B were
      higher than those after the four other maneuvers; there was a significant
      relationship between DLCO and the duration of the preinspiratory maneuver. The
      data are best explained by an alteration in the distribution of the inspired gas
      mixture to areas with different diffusing capacities. In conclusion, the
      preinspiratory maneuvers must be standardized in order to improve the
      reproducibility of the single-breath DLCO measurements.

PMID- 7633740
TI  - Imbalance between 95 kDa type IV collagenase and tissue inhibitor of
      metalloproteinases in sputum of patients with cystic fibrosis.
AB  - A growing body of evidence suggests that neutrophil-derived proteinases play a
      major role in lung tissue damage in cystic fibrosis (CF). Most previous studies
      have focused on serine proteinases such as neutrophil elastase, providing no
      information on the extent to which metalloproteinases participate in proteolytic
      processes in CF. To address this issue, we evaluated the contribution of one of
      the major neutrophil metalloproteinases, i.e., 95 kDa gelatinase (type IV
      collagenase), to the total gelatinolytic activity measured in sputum specimens
      from 27 patients with CF. Compared with asthmatic children (n = 9), CF patients
      had a 6.7 times greater level of total gelatinase activity in sputum revealed by
      zymography. The 95 kDa gelatinase was increased 3.7-fold in the CF subjects
      (2,441 +/- 411 [SEM] arbitrary units [AU] x 10(6) per ml of sputum versus 665 +/-
      201 in asthmatics) and the 88-kDa active form 23.2-fold (2,272 +/- 372 AU x 10(6)
      per ml of sputum versus 98 +/- 43, respectively). Using radiolabeled 3H-gelatin
      as the substrate, we demonstrated uninhibited gelatinolytic activity in all CF
      patients; this activity was significantly correlated to disease severity as
      assessed by pulmonary function tests. Western blotting using anti-tissue
      inhibitor of metalloproteinase (anti-TIMP) and anti-95/88-kDa gelatinase
      antibodies demonstrated a more than 10-fold excess of 95/88 kDa gelatinase over
      TIMP. Bacterial proteinases from Pseudomonas aeruginosa were shown to contribute
      little to the gelatinolytic activity measured in sputum supernatants from
      patients with CF, although culture supernatants from various P. aeruginosa
      strains expressed gelatinolytic activity in vitro. Finally, lung damage, as
      assessed by increased type IV collagen degradation products in sputum, was
      significantly correlated to concentrations of active 88 kDa gelatinase. These
      data argue for a significant role of 95/88 kDa gelatinase in airway damage in CF.

PMID- 7633747
TI  - Tuberculosis outbreak among healthcare workers in a community hospital.
AB  - Twenty-nine healthcare workers (HCW) were exposed to an active case of
      unrecognized drug-susceptible pulmonary tuberculosis in a community hospital for
      as long as 2 h in the emergency room and 10 h in a medical intensive care unit.
      Twelve of the 29 exposed HCW could not be evaluated for tuberculosis infection
      because 10 of them had a previously positive tuberculin skin test and two were
      lost to follow-up. Of the remaining 17 tuberculin skin test negative HCW, 13
      (76%) either converted their skin test to positive (10 HCW) or developed active
      disease (three HCW) after exposure to the index case. The Mycobacterium
      tuberculosis isolates from the three HCW had identical DNA restriction fragment
      length polymorphism (RFLP) patterns when studied by pulsed field gel
      electrophoresis. This case of drug-susceptible tuberculosis was associated with
      unusually high rates of tuberculosis infection and disease in HCW. Prevention of
      similar occurrences in HCW may be difficult because of the short exposure time
      required for transmission of tuberculosis and the absence of consensus on optimal
      respiratory protective measures.

PMID- 7633748
TI  - Systemic gas embolism complicating pulmonary contusion. Diagnosis and management
      using transesophageal echocardiography.
AB  - Systemic air embolism has been frequently reported after penetrating thoracic
      trauma. In blunt thoracic trauma, systemic air embolism has been rarely
      diagnosed, and then only after an invasive procedure such as thoracotomy.
      Transesophageal echocardiography has been recently introduced for the early
      assessment of trauma patients and is considered a sensitive noninvasive procedure
      to diagnose air embolism. We report three cases of systemic air embolism in
      patients with pulmonary contusion secondary to a blunt thoracic trauma requiring
      controlled ventilation. Transesophageal echocardiography was performed for
      evaluation of hemodynamic instability, and it showed air bubbles in the left
      atrium and left ventricle during the insufflation phase, which disappeared during
      apnea. A decrease in airway pressure (release of PEEP, low tidal volume, high
      frequency jet ventilation) significantly reduced the systemic air embolism. We
      concluded that systemic air embolism can occur after blunt thoracic trauma, and
      transesophageal echocardiography enables a rapid and accurate diagnosis that may
      be useful for therapeutic management.

PMID- 7633749
TI  - Fungal infection in HIV-infected persons. American Thoracic Society.

PMID- 7633751
TI  - A flexible pressure pump for cardiovascular studies.
AB  - Pressure pumps are useful in cardiovascular studies and in the evaluation of many
      circulatory devices. Currently available pumps are, however, far from perfect in
      their methods of syncrhonization, flexibility, and frequency response. To
      overcome these disadvantages, this study reports the design of a new pressure
      pump based on a linear motor. The pump can accurately synchronize with an
      animal's heart beats by using a phase-lock loop (PLL) technique. It has great
      flexibility and the ability to generate both arbitrary pressure waves and pure
      sinusoidal waves. The pressure pump has a frequency response of up to 50 Hz which
      is suitable for cardiovascular studies on rats, rabbits, cats and dogs.

PMID- 7633750
TI  - Routine use of beta-adrenergic agonists in asthma.

PMID- 7633752
TI  - Reduction of evoked potential measurement time by a TMS320 based adaptive matched
      filter.
AB  - In some clinical centres, somatosensory evoked potentials are used for the
      assessment of neurological function during surgical procedures on the spine. As
      these potentials are heavily contaminated in background noise, ensemble averaging
      coupled with invasive instrumentation is routinely used to enhance the signal.
      However, this procedure is very time consuming, often taking several minutes. In
      this paper, an adaptive matched filter has been used to dramatically reduce this
      measurement time to around 20 seconds, even when employing non-invasive surface
      electrodes. This filter has been implemented in real-time by using a TMS320C25
      digital signal processor and results are presented for signal acquisition both at
      the L1-T12 and T5-T6 spinal levels. In addition, the adaptive nature of this
      filter allows the tracking of slowly changing parameters within the evoked
      potential with time.

PMID- 7633753
TI  - Preliminary experimental evaluation of an inverse source imaging procedure using
      a decoupled coil detector array in magnetic resonance imaging.
AB  - Recently, we have discussed several of the aspects involved in the detector array
      concept in magnetic resonance imaging where an image is obtained by applying
      inverse source procedures to the data assembled by an array of coil detectors
      surrounding the object. In this work we describe an experimental setup, where a
      detector array was constructed of 9 coils, that gives a coarse resolution of 3 x
      3 pixels. By measuring the induced current signals over this array of coils, a
      relationship is established between the set of signals and the structure of the
      body under investigation. Through matrix inversion, reconstruction of the
      original source from the detected signals is possible. In this preliminary
      experimental setup, we did not use an actual nuclear magnetic resonance signal.
      Instead, a miniature solenoid was used as a source, to simulate a precessing
      magnetic moment.

PMID- 7633754
TI  - Investigation of the arterial and venous upper arm vascular bed.
AB  - Studies concerning vascular changes in hypertension and exercise have shown an
      increasing need to investigate the properties of a complete vascular bed in vivo.
      In this study, the repeatability of a non-invasive method for quantifying
      properties of the vascular bed of an upper arm segment, was investigated in two
      groups of volunteers (age 22-55 years). One group of subjects (n = 9) were
      measured twice at a 15 min interval. The other group (n = 8) were measured 4
      times with each subject measured daily at the same time. The estimated quantities
      included the arterial and venous blood volume, the static arterial compliance,
      the myogenic response of the arm veins and the extravascular fluid volume of the
      tissue under an occluding cuff at the upper arm. They not only describe
      properties of the arterial vascular bed as a whole but also of different sized
      arteries functioning at different intra-arterial pressure. They were derived from
      the fluid shifts under the occluding cuff that arise when cuff pressure changes,
      as determined by electrical impedance and blood pressure measurements. The
      repeatability of the method was well within the physiologically acceptable range
      and of the same order of magnitude as that of established methods. Established
      methods however, provide less information about the properties of a vascular bed
      and result in controversial estimates of the dynamic arterial compliance.
      Furthermore, the method eliminates the need to match subjects in comparative
      studies for arterial blood pressure. These features and the sensitivity of the
      method for (patho)physiological changes, offer the possibility to investigate in
      vivo many still unknown aspects of the peripheral circulation.

PMID- 7633755
TI  - Dynamic characteristics of prosthetic heart valves.
AB  - The relation between flow rate (Q) and transvalvular pressure-drop (DP) is of
      fundamental importance for a prosthetic heart valve tested in steady flow
      conditions. The Q-DP plot can thus be called the static characteristic of the
      valve. While in pulsatile flow, with time (t) as a parameter, the instantaneous
      Q(t)-DP(t) relation can also be obtained. The Q-DP relation forms a phase graph
      on an X-Y plane during a whole cardiac cycle, and can be regarded as the dynamic
      characteristic, which to our knowledge has never been systematically explored
      before. With in vitro experiment the Q(t)-DP(t) relations are presented for five
      different aortic valves. Properly modelling the characteristics of heart valves
      is a key link in modelling the interactions between the ventricle and arterial
      system. Treatments for valves, such as diode analogue and orifice area assumption
      governed by the Gorlin formula, are found unsatisfactory. A simple one
      dimensional flow equation is used to further examine the Q-DP graph, and both the
      dynamic resistance characteristic and the dynamic flow characteristic can be
      obtained. It is found that the dynamic characteristic differs from the static one
      not only in the inertance effect but also in the transient process, which can be
      quite energy-consuming and therefore important. Geometric relations of these
      phase graphs with the transvalvular power loss are discussed. The method of
      dynamic characteristics provides a new way to evaluate the performance of a
      tested valve.

PMID- 7633756
TI  - Reduction of ocular artefacts in source current density brain mappings by ARX2
      filtering.
AB  - Sweep by sweep analysis of event-related potentials (ERP) of the human scalp
      represents a reliable tool for both the diagnosis of neurologic diseases and the
      study of the central nervous system during cognitive tasks. The off-line
      procedure based on stochastic parametric identification and filtering herewith
      described, allows an accurate analysis of single-sweep ERP and a drastic
      reduction of ocular artefacts variously propagating through the skull. Moreover,
      the spatial distribution of the recorded ERP in bidimensional form was enhanced
      by using the Laplacian operator in order to get an estimate of the source current
      density (SCD) flow from the skull into the scalp. Complete single-trial signals
      were filtered according to an autoregressive model of signal generation with 2
      exogenous inputs (ARX2). The ARX2 procedure models the recorded signal as the sum
      of three signals: (a) the background EEG activity, modelled as an autoregressive
      process driven by a white noise; (b) a filtered version of a reference signal
      carrying the average information contained in each sweep; (c) a signal due to the
      ocular artefact propagation. The evaluation of the effect of artefact suppression
      on those channels close to the eyes was compared with standard ordinary least
      squares method (OLS) based on a linear model of the influence of EOG on ERP.
      Finally, the better results obtainable through ARX filtering on sweep-by-sweep
      brain mappings are also presented.

PMID- 7633757
TI  - Is stem length important in uncemented endoprostheses?
AB  - In an uncemented total hip replacement where the femoral stem is thinner than the
      medullary canal it may be hypothesized that the distal portion of the stem has no
      mechanical function. In this study an uncemented total hip replacement has been
      modelled mathematically using finite element analysis and mechanical tests of a
      similar system have been carried out loading implants in cadaveric proximal
      femora. Two implants have been tested mechanically; one with a full length stem
      and the second with the stem shortened, but three implants have been modelled
      with an additional intermediate length stem analysed. Additionally the finite
      element analysis has been done with a high neck resection and a standard level
      resection. The finite element model showed that the full length stem produced
      lower interface contact stress levels under the proximal neck, particularly when
      the nec was resected, and this was borne out by the mechanical testing.

PMID- 7633758
TI  - A virtual five-link model of the thumb.
AB  - Most researchers have modelled the thumb as three rigid links with connections of
      two universal joints (carpometacarpal joint and metacarpo-phalangeal joint), and
      a hinge joint (interphalangeal joint). Although this produces the required number
      of degrees of freedom, the resulting motion is not anatomically accurate. In this
      work, the thumb is modelled as a five-link manipulator with the virtual links
      connected by hinge joints-one for each degree of freedom of the thumb. The axes
      of the hinges are not orthogonal to one another, in the long axis of the bones or
      to the anatomic planes. Four static positions of hand function were analysed-key
      pinch, screwdriver hold, tip pinch, and wide grasp. The virtual five-link model
      of the thumb predicted similar muscle recruitment patterns to published EMG data.
      The force at the distal surface of the trapezium is between 6 and 24 times the
      applied load depending on the posture.

PMID- 7633759
TI  - Two-dimensional elastic properties of human skin in terms of an incremental model
      at the in vivo configuration.
AB  - The two-dimensional biomechanical behaviour and the collagen content of human
      skin samples from different anatomical sites was examined. The axes of minimum
      and maximum shrinkage after excision were determined and correlated with the
      'Langer' cleavage lines. Test equipment was developed to restore the original
      geometry and to measure the loads acting perpendicular to the circumference of
      the skin specimens. These loads were normalized with respect to the thickness and
      collagen content and considered as the in vivo tension generated by the
      surrounding skin area. Using the in vivo geometry of the specimen as reference a
      set of incremental strains was applied. After stress relaxation was completed the
      final values of stresses were recorded and related to the incremental strains.
      The two-dimensional stress-strain relationship was the basis for the evaluation
      of the incremental elastic moduli. Orthotropic mechanical behaviour was found
      mainly in regions of reduced in vivo tension. The relationship between the degree
      of anisotropy at the in vivo configuration and the morphological structure is
      discussed.

PMID- 7633761
TI  - Comment on: The use of strain energy as a convergence criterion in the finite
      element modelling of bone and the effect of model geometry on stress convergence.

PMID- 7633760
TI  - A robust transcutaneous electro-muscle stimulator (RTES): a multi-modality tool.
AB  - This paper introduces a transcutaneous electro-muscle stimulator design that has
      a wide range of output capabilities. Because of this, the unit is referred to as
      a robust transcutaneous electro-muscle stimulator (RTES). The RTES is a constant
      current stimulator that is designed to be capable of generating significant
      tetanic contractions from large muscle groups, such as the quadriceps. It is
      capable of generating complex current pulse profiles and has been tested at pulse
      frequencies greater than 7500 Hz. It is routinely used to generate rectangular,
      bi-phasic pulses in muscle-modelling studies in ranges of widths from 3 to 1000
      microseconds, amplitudes from -50 to +50 mA and frequencies from 10 to 60 Hz. The
      design extrema on pulse width and amplitude, are 1000 microseconds and +/- 100 mA
      respectively. Because of the stimulator's robust output characteristics, it is
      suitable for many types of electro-stimulation studies including pain management,
      edema reduction and more.

PMID- 7633762
TI  - Island inner canthal and glabellar flaps for nasal tip reconstruction.
AB  - A series of inner canthal and glabellar island flaps for nasal tip reconstruction
      based on the angular artery and vein is presented. These flaps have the
      advantages of providing well vascularised tissue of the appropriate colour,
      texture and thickness for external skin and vestibular lining, with a wide arc of
      rotation and satisfactory donor site defect, in a single stage procedure.

PMID- 7633763
TI  - Efficacy of flashlamp-pumped pulsed dye laser therapy for port wine stains:
      clinical assessment and histopathological characteristics.
AB  - Clinicopathological evaluation of flashlamp-pumped dye laser therapy for port
      wine stains was conducted on 474 subjects (135 male and 339 female) ranging in
      age from less than a year to 85 years (median = 17; lower quartile = 7 and upper
      quartile = 28). There was a significant variation in the rate of favourable
      response among lesion sites but the variation in relation to sex, age and
      radiation dose was not significant. Histological investigations of skin biopsy
      specimens from 23 subjects indicated that the mean depth of vessels is the main
      prognostic factor. The critical value (standard error) of the mean depth for a
      favourable response was estimated as 930(50) microns. Applications of this
      estimate to clinical prognosis are discussed.

PMID- 7633764
TI  - Perfusion imaging of skin island flap blood flow by a scanning laser-Doppler
      technique.
AB  - Conventional laser-Doppler perfusion measurements can only obtain information
      from a single site. Since superficial blood flow is heterogeneous, this is a
      serious limitation, particularly in studies of methods to improve skin flap
      survival. A scanning laser-Doppler instrument has been developed which provides
      both an image and quantitative information about perfusion of the superficial
      tissue. We have evaluated this instrument in a circumflex iliac artery island
      flap model in the pig. The validity of the model was demonstrated by fluorescein
      dye injection and histology. Elevation of flaps was found to increase proximal
      flap blood flow but to decrease it in the distal portion. In flaps subjected to
      arterial ischaemia (9 h) and reperfusion we found an early increase in proximal
      flow, which gradually extended distally over the first 40 to 60 min. 16 h later,
      flow had declined, compatible with reperfusion damage to the vasculature. We
      suggest that perfusion imaging may be a valuable technique for investigating the
      mechanisms and extent of reperfusion injury.

PMID- 7633765
TI  - Serial fluorometric assessments of skin perfusion in isolated perfused human skin
      flaps.
AB  - The applicability of serial skin surface fluorometry for repeated assessments of
      skin flap perfusion was investigated using the isolated perfused human transverse
      paraumbilical (TP) skin flap model. The flow rate, perfusion pressure and skin
      surface temperature were kept constant in seven human TP skin flaps and a low
      dose of fluorescein (3 x 10(-5) M) was used for each assessment. It was observed
      that the mean values for total dye fluorescence measured by a fluorometer and the
      maximum distance of perfusion estimated by dye fluorescein index remained
      consistent in five repeated assessments at 15 min interval. The variation in the
      maximum distance of perfusion within each TP skin flap over 5 repeated
      assessments was also relatively small, as judged by the mean coefficient of
      variation (6.1%; SEM 0.4%). Furthermore, a highly significant correlation between
      microsphere (15 microns) radioactivity index and dye fluorescence index was
      observed at corresponding locations in these seven TP skin flaps (r = 0.81; p <
      0.001, n = 75). Taken together, these observations indicate that serial skin
      surface fluorometry provided consistent repeated assessments of skin perfusion in
      human skin flaps in vitro and the dye fluorescence index provided a consistent
      assessment of skin perfusion distance along the length of the TP skin flap. These
      observations lead us to speculate that critical (threshold) dye fluorescence
      index determined at various postoperative time points should be useful for
      prediction of skin viability in clinical skin flaps; thus, a clinical
      investigation is recommended.

PMID- 7633766
TI  - Upper eyelid reconstruction with mucosa-lined bipedicled myocutaneous flaps.
AB  - We present a method for morphodynamic reconstruction of the upper eyelid for
      large full thickness defects. The main features of this single-stage operation
      are: reconstruction of the conjunctiva by free mucosal graft from the oral
      cavity; mobilisation of a bipedicled myocutaneous flap from the preseptal (or
      orbital) portion of the lid, anchoring of the levator to this flap and
      transposition of a temporofrontal flap to reconstruct the donor site of the
      bipedicled flap. This method is simpler and above all less invasive than other
      techniques used at present and at the same time allows for a good functional and
      aesthetic reconstruction.

PMID- 7633767
TI  - Clinical study of symbrachydactyly of the foot.
AB  - Seventeen patients with symbrachydactyly of the foot are described. Patient
      characteristics including sex, the side of the affected foot, age at first
      medical examination, and condition of the nails were recorded. Compared with the
      unaffected side, the lengths of the proximal phalangeal and metatarsal bones were
      significantly shorter. The abnormalities of the feet were classified into four
      types: typical axial, atypical axial, medial ray, and rudimentary. The anomaly
      progresses from hypoplasia of the central rays to a deformity of the great toe,
      but rarely involves the fifth toe. The fact that this differs from
      symbrachydactyly of the hand is of considerable interest.

PMID- 7633768
TI  - A new operation for syndactyly and polysyndactyly of the foot without skin
      grafts.
AB  - A new surgical technique is described for the treatment of polysyndactyly and
      syndactyly of the toes. The lateral aspects of the toes are covered by only the
      interdigital skin without any skin grafts. A subcutaneous pedicled pentagon flap
      designed on the plantar skin is used for the repair of the base of the
      interdigital space. 12 interdigital spaces involved in polysyndactyly of the 4th,
      5th and 6th toes and 6 interdigital spaces involved in incomplete syndactyly of
      the toes have been treated. Good aesthetic and functional results were achieved.

PMID- 7633769
TI  - Free snuff-box flap for reconstruction of the wrap-around flap donor site.
AB  - The big toe donor site of the wrap-around flap has been reconstructed immediately
      after elevation of the flap with a snuff-box flap from the dorsum of the
      recipient hand in 6 patients. Rapid wound healing and a satisfactory appearance
      were achieved.

PMID- 7633770
TI  - Shave excision of benign papular naevocytic naevi.
AB  - Patients frequently request removal of benign papular naevi for cosmetic or
      functional reasons. Shave excision plus electrocautery is probably the most
      widely used method of removal, but this method is said to result in retained hair
      or pigment if deeply pigmented or hairy naevi are treated. In a prospective
      study, 82 benign papular naevi of all types were treated by shave excision using
      hot-wire electrocautery for haemostasis. Details of the naevi were accurately
      recorded before treatment and reassessment of shave sites carried out at 6-8
      months. At review, a scar was visible at only 63% (52/82) of shave sites and all
      of these were cosmetically acceptable. Only 27% (15/55) of the initially
      pigmented naevi retained pigment and only 24% (5/21) of the initially hairy naevi
      regrew hair. Shave excision and electrocautery of benign naevi, including hairy
      and deeply pigmented ones, produce excellent cosmetic results. The patient must
      be warned that there is a potential risk of a scar or pigment remaining after
      shave excision of any naevus and for hair regrowth after shave excision of hairy
      naevi.

PMID- 7633772
TI  - Repair of alar clefts, associated with nasal skin lumps and median clefts of the
      upper lip and alveolus.

PMID- 7633771
TI  - A bolster suture technique for ear reconstruction for microtia without skin
      necrosis.
AB  - A new bolster suture technique to prevent skin necrosis in microtia ear
      reconstruction is presented. An outer series of bolsters is placed distant from
      the ear framework in a zigzag fashion, the temporal skin being gathered on the
      framework. In this way, the skin flap overlying the framework is relaxed and has
      sufficient blood flow. Therefore the skin flap can be thinned with little risk of
      necrosis. Furthermore, the contour of the reconstructed auricle is accentuated
      because of the thin relaxed overlying skin. Seven ears with microtia were
      reconstructed using this method. The results were satisfactory, except for one
      auricle which became slightly congested at the conchal portion due to excessive
      thinning. There were no haematomas or skin necrosis.

PMID- 7633773
TI  - Heterotopic brain tissue in the scalp.
AB  - A posterior midline cutaneous lesion in the scalp of a 15-month-old child was
      excised. Clinical examination, extensive investigations and finally surgery
      revealed no intracranial connection. Histologically, the lesion was composed of
      well differentiated meningeal, glial and cerebral tissues, establishing it to be
      heterotopic brain tissue. Even when all preoperative procedures exclude the
      diagnosis of cephaloceles, surgeons should keep in mind the possibility of an
      intracranial connection of any midline scalp lesion in a child and the subsequent
      risk of meningitis.

PMID- 7633774
TI  - John Turner Hueston.

PMID- 7633775
TI  - Multiple uses of the hypodermic needle.

PMID- 7633776
TI  - Day care surgery for prominent ears.

PMID- 7633777
TI  - The sacral anterior root stimulator as a means of managing the bladder in
      patients with spinal cord lesions.

PMID- 7633779
TI  - Cochlear implants.

PMID- 7633780
TI  - Visual prostheses based on direct interfaces with the visual system.

PMID- 7633778
TI  - Implants for tremor.
AB  - Chronic or contingent electrical stimulation at various sites in the region of
      the ventrolateral nucleus of the thalamus can suppress contralateral intention
      tremor and the resting tremor seen in Parkinson's disease and idiopathic tremor.
      The procedure appears to carry less risk, in producing physical or cognitive
      impairment, than stereotactic ablation. However, the procedure has been tried in
      few centres to date and long term follow-up studies are needed to place this
      treatment in its true clinical perspective. It is important to assess patients'
      needs very carefully to ensure that their functional objectives will be best met
      by treatments of this kind, and that the requirement for regular monitoring and
      periodic reassessment can be fully met during long term follow-up.

PMID- 7633781
TI  - Neuroprostheses used to restore male sexual or reproductive function.

PMID- 7633782
TI  - Neuromodulation for pain and epilepsy.

PMID- 7633783
TI  - Development of an electrically-stimulated skeletal muscle neoanal sphincter.

PMID- 7633784
TI  - Lower limb functional neurostimulation.

PMID- 7633785
TI  - Upper extremity neuroprostheses using functional electrical stimulation.

PMID- 7633786
TI  - Neuroprostheses for ventilatory support.

PMID- 7633787
TI  - Implants for spasticity.
AB  - In carefully selected groups of patients, intrathecal baclofen therapy offers
      well-proven benefits in reducing spasticity, notably in cases of spinal injury
      and multiple sclerosis. The initial costs of implantation are high, and there
      must be a long-term commitment by both patient and medical personnel to careful
      and proper management. Nevertheless, in suitable cases, the techniques should
      generally be properly considered before proceeding to any irreversible
      destructive neurosurgical procedure.

PMID- 7633788
TI  - Hughes syndrome: antiphospholipid antibodies move closer to thrombosis in 1994.

PMID- 7633789
TI  - Rheumatology in general practice.

PMID- 7633790
TI  - Lack of temporal association of iridocyclitis with IgG reactivities to core
      histones and nucleosome subparticles in pauciarticular juvenile chronic
      arthritis.
AB  - This study aimed to measure IgG reactivities to DNA-free nucleosome subparticles
      (H2AH2B, H3H4) and nucleosome subparticles (H2AH2B-DNA, H3H4-DNA) and to evaluate
      the temporal relation of these reactivities, as well as those to single core
      histones, with iridocyclitis (IC) in patients with antinuclear antibody positive
      (ANA+) pauciarticular juvenile chronic arthritis (JCA). Reactivities to nuclear
      substrates were determined by enzymatic immunoassays in 120 sera from 45 children
      with ANA+ pauciarticular JCA. Significantly elevated IgG levels to H3 and H4, to
      DNA-free nucleosome subparticles, and to the nucleosome subparticle H3H4-DNA were
      present in patients with ANA+ pauciarticular JCA; no evidence of recognition of
      conformational epitopes was found. In both horizontal and follow-up studies, no
      relation between the reactivities studied and the development, presence, or
      history of IC was found. Our results show the absence of a relation of antibodies
      to histone molecules or to nucleosome subparticles with IC in patients with ANA+
      pauciarticular JCA.

PMID- 7633791
TI  - Abnormal collagen cross-linking in the cartilage of a diastrophic dysplasia
      patient.
AB  - The abnormal organization of the cartilage collagen in diastrophic dysplasia is
      not generally reflected in the levels of the major stabilizing cross-link,
      hydroxylysyl-pyridinoline. However, in one case there was a marked decrease in
      the pyridinoline concomitant with the appearance of two unknown components in the
      cross-link region of the chromatogram. A decrease in cross-linking of this
      magnitude could lead to mechanically weakened cartilage. Insufficient material
      was available to characterize these unknown components. The disorganization of
      cartilage in some cases of diastrophic dysplasia could therefore be due to post
      translational modifications, including defective cross-linking.

PMID- 7633792
TI  - Assessment of bone mineral density in women with Marfan syndrome.
AB  - Although radiological studies suggest that Marfan syndrome is associated with
      osteopenia, investigations utilizing measurements of bone mass have yielded
      conflicting results. To address this question further, we measured bone mineral
      density (BMD) in 14 women with Marfan syndrome at the right hip and lumbar spine
      by dual energy X-ray absorptiometry (DXA). Results were compared with the age-
      and weight-matched reference population supplied by the DXA manufacturer, and
      with our own control population of normal women, the latter being matched for
      height, in addition to age and weight. We found that BMD was very similar in our
      Marfan women as compared with the two reference populations, at the lumbar spine
      and femoral neck, while trochanteric BMD was reduced. However, the relationship
      between an isolated reduction in trochanteric BMD and future fracture risk is
      unclear, and, on the basis of our results, we conclude that Marfan syndrome is
      not associated with a clinically significant increase in the risk of osteoporotic
      fracture.

PMID- 7633793
TI  - OM-89 modulation of chronic inflammation: relevance to clinical use.
AB  - The modulatory effects of a glycoprotein-rich endotoxin-free extract of
      Escherichia coli (OM-89) have been studied using the cotton pellet model of
      chronic inflammation in the male Wistar rat. OM-89 had a suppressive effect on
      the size of granuloma surrounding implanted cotton pellets at both 4 and 40 mg/kg
      given three times weekly. The lower dosage of 4 mg was effective throughout and
      there was little to be gained by increasing the dose as further reduction of
      granuloma size was not obtained. Whether given prior to, at the same time as, or
      after an inflammatory stimulus, OM-89 had suppressive effects. However, if given
      before, animals at first went through a phase of 'sensitization' before
      suppressive effects were seen on further exposure to OM-89 antigens, a phenomenon
      which might have bearing on clinical findings in rheumatoid arthritis. In animals
      presensitized to a cotton pellet, OM-89 was statistically as effective as
      indomethacin in suppressing a second granuloma. OM-89 combined with indomethacin
      showed additive effects and was highly effective. The results indicate that OM-89
      could be efficacious in the treatment of chronic inflammatory conditions and
      there is the possibility that in appropriate circumstances OM-89 might replace
      some drugs currently used and in others reduce their dosage.

PMID- 7633794
TI  - Prognostic factors in rheumatoid arthritis. Comparative study of two subsets of
      patients according to severity of articular damage.
AB  - Clinical and biological profiles at the onset of the disease, obtained
      retrospectively, and human leucocyte antigen typing were studied in 47 rheumatoid
      arthritis (RA) patients with severe articular damage (group 1) and in 47 patients
      with limited radiological abnormalities (group 2). The two groups were matched
      according to disease duration (mean: 8.1 yr). Systemic manifestations were more
      frequent in group 1. Erythrocyte sedimentation rate (ESR), platelet counts, C
      reactive protein (CRP), rheumatoid factor and IgG titres were higher and
      haemoglobin level lower in group 1. HLA class II genotyping demonstrated that
      95.7% of patients in group 1 were Dw4, Dw14 or DR1 as compared to 55.3% in group
      2 and 37.1% in normal controls. Two RA-linked DRB1 genes were detected in 34.1%
      of patients in group 1, vs 8.5% in group 2 and 7.9% in controls. Multiple
      logistic regression analysis demonstrated that ESR, CRP and genetic markers were
      the most relevant independent variables and when combined could indicate the
      outcome in early RA. These data confirmed that different RA subtypes with
      different prognoses could be associated with particular clinical, biological and
      genetic profiles. Moreover, some of these factors could serve as predictive
      markers for outcome at the onset of RA.

PMID- 7633795
TI  - Ultrasound measurement of skin thickness in systemic sclerosis.
AB  - Sclerotic skin change in systemic sclerosis (SSc) usually accompanies increased
      skin thickness. In order to quantify the cutaneous changes and to clarify the
      changes in the 'uninvolved' skin in systemic sclerosis (SSc), we measured the
      skin thickness on the chest, the forearms and the hands of 79 patients with SSc
      and 81 healthy controls with a B-mode ultrasound (30 MHz) apparatus. The
      thickness of the 'uninvolved', as well as the 'involved' skin in patients with
      SSc was significantly greater than that of healthy controls. Increased skin
      thickness on the forearms and/or the hands showed a 64.6% sensitivity and a 100%
      specificity for SSc. These results indicated that the skin which appears to be
      'uninvolved' in patients with SSc is already pathologic, as shown by increased
      thickness. Moreover, measurement of skin thickness may be beneficial in the
      diagnosis of this disease at an early stage.

PMID- 7633796
TI  - Does mixed connective tissue disease exist in India?
AB  - One thousand consecutive patients with systemic connective tissue diseases were
      screened clinically and serologically to determine the existence of mixed
      connective tissue disease (MCTD) in the Indian population. After completion only
      three patients could be diagnosed as having MCTD using the standard diagnostic
      criteria. The results of this study point to MCTD existing but it appears to be a
      rare entity in the Indian population.

PMID- 7633797
TI  - Breast feeding, other reproductive factors and rheumatoid arthritis. A
      prospective study.
AB  - The evidence regarding reproductive events as risk factors for rheumatoid
      arthritis (RA) is not conclusive. In the present study a population-based cohort
      consisting of 63,090 women were followed from 1961 to 1989. Detailed data on
      reproductive factors were collected through personal interviews in the period
      1956-9. The endpoint used was mention of RA on the death certificate. Mortality
      rate ratios were estimated by Poisson regression, controlling for various
      demographic variables. During 1,485,400 person-yr of observation, a total of 355
      cases with RA mentioned on the death certificate were identified. Total time of
      lactation was associated with a decreased mortality of RA, with an approximate
      dose-response relationship. The results did not support a role of parity, age at
      first and last birth, or age at menarche and menopause in the development of RA.
      This protective effect of lactation on the development of RA has not previously
      been described, and since a definite biological explanation is lacking, the
      association should be confirmed in other populations.

PMID- 7633799
TI  - Massive pericardial effusion in scleroderma: a review of five cases.
AB  - Medical records of five patients with scleroderma (SSc), each of whom had
      pericardial effusion with an estimated volume of more than 200 ml, were reviewed
      to study the clinical and immunological significance of massive pericardial
      effusion in SSc. Diffuse SSc (4/5), with a wide area of pigmentation (4/5),
      flexion contracture (4/5), oesophageal hypomotility (5/5), pulmonary fibrosis
      (4/5) and autoantibodies to topoisomerase I (3/5) were the common features in
      this group. High protein, lactate dehydrogenase and low white blood cell count
      were the characteristics of pericardial fluid. None of the patients had signs of
      acute pericarditis. Four of the five cases died within 9 months of the diagnosis
      of pericarditis; two with renal failure, one with cardiac tamponade and another
      with sudden death. The pericarditis in diffuse SSc, especially in cases with anti
      topoisomerase I, may be characterized by a chronic form of pericarditis with poor
      prognosis, often complicated by renal failure.

PMID- 7633798
TI  - Rheumatoid arthritis patients cannot accurately report signs of inflammatory
      activity.
AB  - If patients with rheumatoid arthritis (RA) could self-report symptoms in a manner
      which correlated with laboratory measures of inflammation this would be a
      valuable research or clinical tool. Developing such a tool means ensuring that
      the questions are understood and a variety of combinations of signs, symptoms and
      joints explored. Preliminary studies in two groups of 20 RA out-patients
      established an acceptable self-report questionnaire format by which patients
      could identify their joints. Fifty RA out-patients completed these self-report
      forms on four grades of each of four symptoms (pain, heat, stiffness, swelling)
      in each of 64 joints, as well as visual analogue scales (VAS) on overall pain and
      perceived disease activity. A clinical research assistant recorded the Thompson
      Kirwan articular index (TKAI) and plasma viscosity (PV) was measured. The data
      were analysed in a variety of ways in an attempt to construct a self-report
      articular index (SRAI) which correlated with PV. The strongest models were then
      tested in 11 in-patients undergoing a flare of their disease. No adequate SRAI
      could be constructed which correlated with PV and in addition neither VAS score
      correlated with PV. There was a moderate correlation between the TKAI and a
      patient SRAI using the same joints, symptoms and weightings (r = 0.6, P < 0.01).
      Patients can clearly report different grades of multiple symptoms in multiple
      joints, but such reports cannot be shown to be a reliable indicator of
      inflammatory activity.

PMID- 7633800
TI  - Salmonella pyomyositis in patients with the human immunodeficiency virus.
AB  - Pyomyositis is a common disease in the tropics, mostly due to Staphylococcus
      aureus. We report two patients infected with the human immunodeficiency virus
      (HIV) who presented with fever and unilateral limb swelling and in whom
      pyomyositis was diagnosed in quadriceps and gluteus major, respectively.
      Salmonella enteritidis was isolated in both, with recurrent episodes of muscle
      involvement and secondary osteomyelitis in one case. Non-typhi Salmonella
      pyomyositis may occur in HIV + patients with a relapsing and aggressive clinical
      course in some cases.

PMID- 7633801
TI  - Cerebral venous thrombosis and acquired protein S deficiency: an uncommon cause
      of headache in systemic lupus erythematosus.
AB  - A 42-yr-old woman with hypertension and renal involvement due to systemic lupus
      erythematosus (SLE) developed unilateral headache followed by the sudden onset of
      confusion and a grand mal convulsion. Cerebral computed tomography was normal. A
      magnetic resonance imaging angiogram revealed cerebral venous thrombosis and a
      venous infarct. Nephrotic syndrome had resulted in an acquired protein S
      deficiency. A review of previous cases suggests that either renal disease with
      proteinuria or features of the antiphospholipid syndrome are prerequisites for
      the development of cerebral venous thrombosis in SLE. Low free-protein S levels
      may be an additional risk factor. Furthermore it is likely that this condition is
      underdiagnosed.

PMID- 7633802
TI  - Diltiazem induces remission of calcinosis in scleroderma.
AB  - There is no widely accepted treatment for the calcinosis which occurs in
      scleroderma and dermatomyositis. We report a case of a 62-yr-old woman with
      active scleroderma complicated by tuberose calcinosis. The calcinosis, which had
      previously been unchanged for several years, regressed over a 2-yr period during
      which diltiazem was used to treat hypertension. This effect could not be
      explained by altered disease activity or renal function but, we suggest, may be
      due to inhibition of calcium influx into cells. This treatment merits further
      evaluation.

PMID- 7633803
TI  - Symptomatic splenic infarction complicating adult Kawasaki disease.

PMID- 7633804
TI  - Combination therapy in rheumatoid arthritis.

PMID- 7633805
TI  - How does neurophysiological assessment influence the management and outcome of
      patients with carpal tunnel syndrome?

PMID- 7633806
TI  - Autoimmune phenomena associated with cutaneous aseptic necrosis during interferon
      alpha treatment for chronic myelogenous leukaemia.

PMID- 7633807
TI  - Fluoroquinolone-induced tenosynovitis of the wrist mimicking de Quervain's
      disease.

PMID- 7633808
TI  - Lupus-like syndrome in patients treated for acne.

PMID- 7633809
TI  - Discitis caused by Corynebacterium pseudodiphtheriticum following ear, nose and
      throat surgery.

PMID- 7633810
TI  - Scalp reductions.

PMID- 7633811
TI  - Merkel cell carcinoma. Diagnosis and treatment.
AB  - BACKGROUND: Merkel cell carcinoma is an uncommon malignancy of the skin that
      often portends a poor prognosis. Since its first description by Toker in 1972, a
      plethora of case reports and articles regarding the etiopathogenesis and
      treatment have been published spanning multiple medical and surgical disciplines.
      Much confusion still exists regarding the diagnosis and treatment of this ominous
      tumor. OBJECT: Through extensive review of the medical, surgical, and
      pathological literature, to collate the observations of multiple investigators
      and summarize these findings. METHODS: Articles from journals of multiple
      subspecialties were carefully reviewed with particular emphasis placed on
      epidemiology, prognosis, histology, immunohistochemistry, electron microscopy,
      tumor origin, treatment, and work-up of Merkel cell carcinoma. RESULTS: Merkel
      cell carcinoma is an aggressive malignant neoplasm. Local recurrence develops in
      26-44% of patients despite therapy. Up to three-fourths of patients eventually
      develop regional nodal metastases with distant metastases occurring in one-third
      of all patients. Reported overall 5-year survival rates range from 30% to 64%.
      CONCLUSION: Treatment recommendations unfortunately are based more on anecdotal
      than scientific data because of the rarity of the tumor and its recognized high
      risk. Most authors recommend wide local excision of the primary lesion and
      regional lymph node resection if lymph nodes are palpable followed by x
      irradiation of both the postsurgical bed and lymph node basin. The role of
      elective lymph node resection in the absence of clinically positive nodes remains
      controversial.

PMID- 7633812
TI  - Laser treatment of scars.
AB  - BACKGROUND: Erythematous and hypertrophic scars may occur after surgical
      procedures. This paper describes a novel technique for their resolution.
      OBJECTIVE: The purpose of this paper is to describe long-term results of treating
      erythematous, hypertrophic scars with the flashlamp-pumped pulsed dye laser
      (FLPDL). METHODS: Forty-eight patients who presented with
      erythematous/hypertrophic scars were treated with the FLPDL with or without
      intralesional triamcinolone. Patients were evaluated by physicians on a 25%
      increment of objective improvement. RESULTS: Seventy-three percent of scars
      appearing on the face for less than 1 year totally resolved in an average of 2.3
      treatments. Twenty percent of scars on the face for greater than 1 year had a
      total resolution in 4.4 treatments with an average improvement of 88%. Scars on
      nonfacial areas for less than 1 year had a 25% incidence of total resolution over
      an average of 2.5 treatments with an average improvement of 81%. Scars in
      nonfacial distributions over 1 year of age had a 12% total resolution with an
      average 62% improvement over 2.2 treatments. CONCLUSION: The FLPDL is a useful
      adjuvant in the treatment of erythematous, hypertrophic scars.

PMID- 7633814
TI  - Endoscopic surgical correction of glabellar creases.
AB  - BACKGROUND: A number of alternatives exist for the temporary correction of
      glabellar creases and frown lines. The traditional "open" operative procedure has
      often involved a large incision to gain access to the depressor muscles that are
      responsible for the deformity. While useful for patients with multiple or more
      significant deformities, patients with isolated glabellar creases and frown lines
      have been reluctant to consider an extensive surgical procedure, with its
      attendant morbidity, for an isolated problem. OBJECTIVE: The purpose of this
      report is to describe a new technique of endoscopic corrugator muscle resection,
      without the need for the traditional lengthy scalp incision. METHODS: Traditional
      criteria for patient selection was employed. A series of 10 consecutive patients
      with vertical mid-forehead glabellar-eyebrow frown lines were treated by
      endoscopic corrugator muscle resection and evaluated. RESULTS: The procedure was
      efficacious in reducing the frown-muscle complex prominence and rhytids in the
      mid-forehead area. Circumstances of heavy folds, hyperactive muscle function, or
      premature furrows in patients with good skin tone appear to be most suitable for
      this technique. CONCLUSION: With the introduction of a more acceptable, less
      problematic surgical solution, deformities in the forehead-eyebrow area can be
      readily addressed surgically. The procedure is a cost-effective alternative to
      temporary techniques improving aesthetic problems in the forehead-eyebrow area.

PMID- 7633813
TI  - Lymphoepithelioma-like carcinoma of the skin treated by Mohs micrographic
      surgery.
AB  - BACKGROUND: Lymphoepithelioma-like carcinoma of the skin (LELCS) is a rare
      malignant tumor thought to be of adnexal origin. Because of its rarity, treatment
      parameters have not been defined. OBJECTIVE: To examine the role and success of
      Mohs micrographic surgery in the treatment of LELCS versus other forms of
      treatment previously documented in the literature. METHODS/RESULTS: A review of
      the previous reported cases and their treatment outcomes was compared with the
      present case. Three of the 12 previously reported cases were incompletely treated
      with initial surgical management, with one patient subsequently dying of
      metastatic tumor. The present case was treated with Mohs micrographic surgery for
      recurrent LELCS, following initial treatment with electrodessication and
      curettage, and is without evidence of disease 20 months postoperatively.
      CONCLUSION: LELCS may be successfully treated by Mohs micrographic surgery.

PMID- 7633816
TI  - The Burow's triangle scalp reduction. A new and improved technique for paramedian
      scalp reduction.
AB  - BACKGROUND: The paramedian incision for scalp reduction has many advantages over
      the median (midline-sagittal) incision. OBJECTIVE: This report describes a method
      by which the paramedian incision may be modified to provide even more advantages.
      METHODS: In 20 patients with male pattern alopecia, an anterior and posterior
      paramedian incision was performed along contralateral borders of the bald scalp.
      The two incisions were joined in the central scalp by a trans-coronal incision.
      The tissue movement that followed was similar to that of a Burow's triangle
      advancement flap. RESULTS: The new configuration provided maximal visual access
      with improved tissue mobilization and ease of handling. Because the tension
      bearing vector was directed parallel to the transcoronal incision, there was
      little tendency for the scar to widen. Because posterior "slots" or "troughs"
      were not created, additional corrective procedures were not necessary.
      CONCLUSION: The Burow's triangle scalp reduction design is cosmetically and
      mechanically more advantageous than traditional median and unilateral paramedian
      designs of equivalent length.

PMID- 7633815
TI  - Split-thickness skin grafting of leg ulcers. The University of Miami Department
      of Dermatology's experience (1990-1993).
AB  - BACKGROUND: Skin grafting for large and recalcitrant lower extremity ulcers is a
      commonly used therapy. However, the success rate for grafts performed by
      dermatologists is largely unknown. OBJECTIVE: To analyze our experience with
      meshed split-thickness skin grafts for leg ulcers. METHODS: We retrospectively
      analyzed all hospitalized dermatology patients who underwent meshed split
      thickness skin grafting for lower extremity ulceration due to a variety of causes
      performed by the Department of Dermatology at the University of Miami over a 3
      year period (1990-1993). RESULTS: Twenty-nine patients with 36 ulcers were
      grafted. Greater than 90% of ulcers had initial graft take. At long-term follow
      up, 52% of ulcers were healed, 26% were partially healed, and 22% recurred.
      CONCLUSION: We conclude that meshed split-thickness skin grafting is a safe and
      effective therapy for recalcitrant lower extremity ulcers.

PMID- 7633817
TI  - Vitiligo: surgical repigmentation of leukotrichia.
AB  - BACKGROUND: Patients with vitiligo frequently have premature gray hair. Until
      recently the literature was silent about its management. While surgically
      treating vitiligo, we incidentally observed repigmentation of gray hair.
      OBJECTIVE: Based on our observations we undertook this study to see the effect of
      surgical treatment of vitiligo on repigmentation of leukotrichia, as well as to
      evaluate the percentage of repigmentation, if any, in the different hair-bearing
      areas, and the time taken for it. METHODS: A case series of eight patients with
      nine patches of localized, stable, and refractory vitiligo with leukotrichia of 3
      12 years duration is presented. The patients were followed up for 2-6 years. One
      patient was lost from follow-up after 2 months. The vitiligo was treated by
      dermabrasion and thin split-thickness skin grafting under local anesthesia, as
      outpatients. RESULTS: Repigmentation of the hair occurred in all the areas but it
      was seen earlier (3 months) and was more complete in the eyebrows (70-95%). In
      the scalp and the beard areas it started later (6-9 months) and was around 50-60%
      only. The degree of pigmentation increased until about 3 years after surgery. No
      complications in the form of graft loss or alopecia were observed. CONCLUSIONS:
      Partial to near-total repigmentation of leukotrichia can be achieved surgically.
      Contrary to the present theory, we hypothesize that melanocytes also migrate from
      the repigmented epidermis to the hair follicle, resulting in repigmentation of
      the hair.

PMID- 7633818
TI  - Ischemic complications of tubular gauze dressings.
AB  - BACKGROUND: Ischemic pressure complications associated with tubular gauze digital
      dressings have been occasionally reported in the medical literature. Previous
      authors have implicated specific mechanisms. We report a 10th case of this type
      of complication and hypothesize that a "Chinese finger trap" mechanism was
      responsible. OBJECTIVE: To compare pressures generated using different
      application techniques of tubular gauze digital dressings. METHODS: A simple
      device to measure dressing pressure was constructed. Comparative pressure
      measurements using different application techniques were obtained. RESULTS: Too
      many layers, excess longitudinal traction during application, using more than a
      90 degrees twist during application, and rolled proximal dressing edges all
      increased measured pressures significantly. CONCLUSIONS: Physicians and other
      health care providers involved in the application of these dressings should be
      aware of their correct application and the mechanisms that may produce
      complications.

PMID- 7633819
TI  - Shave excision and phenol peeling of generalized verrucous epidermal nevus.
AB  - BACKGROUND: Generalized verrucous epidermal nevus is a disorder characterized by
      papulokeratotic and verrucous plaques involving a large area of the skin. This
      disease has been associated with a number of malformations including osseous,
      neurological, and ophthalmologic anomalies. OBJECTIVE: To report clinical and
      histologic features of verrucous epidermal nevus that developed in association
      with osseous anomalies, and the surgical technique employed. METHODS: Treatment
      consisted of razor blade shaving using a dermatome, followed by phenol peeling on
      the pigmented areas of the face. RESULTS: The described procedure resulted in a
      cure of the verrucous epidermal nevus with good cosmetic outcome. CONCLUSION:
      Generalized verrucous epidermal nevus can be successfully managed by surgical
      excision using a razor blade mounted on a dermatome.

PMID- 7633820
TI  - Acne keloidalis nuchae. Tissue expansion treatment.
AB  - BACKGROUND: Acne keloidalis nuchae (AKN) is a chronic idiopathic reaction
      responsible for a great deal of discomfort in patients, and requires radical
      treatment to be eradicated. OBJECTIVE: To analyze the technique used for and the
      results of a case of AKN treated with tissue expansion, which was tracked for 2
      years after the initial study. METHODS: A patient with AKN was treated with
      chronic tissue expansion, total resection, and reconstruction of the injured area
      by advancing the flap of the expanded scalp. Local radiotherapy was applied to
      the resultant scar. RESULTS: After 2 years' follow-up we did not observe a
      recurrence of AKN, and a good cosmetic result was achieved. CONCLUSION: Tissue
      expansion has a role in surgical management of AKN. Staged excision, skin
      grafting, and nonsurgical treatments are also options, however they must be
      individualized to the case at hand.

PMID- 7633822
TI  - Extensive head burns corrected by scalp extension.
AB  - BACKGROUND: Scalp extension has been revealed as a good corrective method for
      androgenetic alopecia and it is possible to foresee its other probable
      applications in the field of increasing hair-bearing areas. OBJECTIVE: The
      performance of Frechet's scalp extender in selected head burn cases allows the
      possibility of maintaining a high degree of social presentability during the
      patient's entire treatment period, on condition that this procedure or others are
      repeated. METHODS: The author discusses his experience in correcting an extensive
      head burn and the performance of Frechet's extender. CONCLUSION: In our
      experience scalp extension showed itself to be a valid method for the correction
      of a burned area, reducing it considerably and reducing total treatment time
      compared with traditional techniques. Also the patient has the advantage of
      normal social presentability during the entire treatment period.

PMID- 7633821
TI  - Inflammatory cutaneous metastases from cloacogenic carcinoma of the anus.
AB  - BACKGROUND: There are a few tumors that exhibit inflammatory cutaneous
      metastases. This pattern is particularly difficult to diagnose since it can mimic
      erysipelas or lymphangitis. OBJECTIVE: This is a presentation of a 69-year-old
      woman diagnosed with poorly differentiated cloacogenic carcinoma who
      simultaneously was noted to have an abdominal rash. A biopsy confirmed cutaneous
      metastasis of her carcinoma. METHODS: Previously published literature on
      cutaneous metastases were reviewed and summarized. RESULTS: This is the first
      reported case of an inflammatory cutaneous metastasis arising from cloacogenic
      carcinoma. CONCLUSION: Cutaneous metastases can present in various forms,
      including the inflammatory pattern. Because this form mimics other conditions, it
      is prudent to biopsy any suspicious skin lesion in cancer patients, as it may
      considerably affect prognosis.

PMID- 7633823
TI  - An unusual case of early malignant transformation in a spiradenoma.
AB  - BACKGROUND: Review of the literature reveals that malignant spiradenomas are rare
      and may be fatal, and typically manifest as rapid enlargement in long-standing
      spiradenomas. OBJECTIVE: The present tumor was removed 2 months after it was
      first noted by the patient. A case of what we believe is the earliest stage of
      malignant transformation within spiradenoma is reported. METHODS: Case report and
      literature review. RESULTS: The region with malignant transformation was
      characterized by nuclear pleomorphism, loss of two cell types, and increased
      mitotic activity with atypical mitoses. Small infiltrating duct-like structures
      were seen. The large aggregates and sheets of malignant cells described in long
      standing tumors were not seen. CONCLUSION: We ascribe the early detection of this
      tumor to increased public awareness of the importance in seeking early treatment
      of skin lesions. Histologic examination of this stage may eventually outnumber
      the now more commonly described latter stages.

PMID- 7633824
TI  - Direct access bill.

PMID- 7633825
TI  - Cutaneous and subcutaneous endometriosis.

PMID- 7633827
TI  - Dermoplaning "necrotic" full thickness grafts to improve their temporary cosmesis
      and permanent contouring.

PMID- 7633826
TI  - Tumescent dermabrasion.

PMID- 7633828
TI  - EMLA for effective pain relief following chemical peeling.

PMID- 7633829
TI  - Lipoproteins in hypoxic tumor cells as traps of free radicals.
AB  - We examined the role of main cell protective mechanisms in retaining the high
      resistance of ascitic cells (EAC, ZAH) to lipid peroxidation with respect to
      different stages of tumor-organism metabolic interactions. The following
      mechanisms were studied: (1) the activity of main EAC enzymatic antioxidants (GSH
      Px, SOD); (2) changes in lipid metabolism, especially the content of the main
      PUFA (linoleic and arachidonic fatty acids) in EAC cells; (3) comparison of
      intracellular resistance between EAC/ZAH cytoplasmic sections (containing LP
      granules or not) to lipid peroxidation (initialized directly by UV-light). We
      found that the high resistance to lipid peroxidation was typical for cytoplasma
      sections (without LP-granules) on all stages of tumor development in vivo. The
      intracellular LP-granules become the main sensitive targets for FR-action, but
      only in the chronic hypoxia state of EAC/ZAH tumor cells. The latter effect
      developed in close correlation with the following metabolic interactions: (1)
      increasing the proportion of PUFA (especially, arachidonic and linoleic acids)
      transported to EAC tumor cells from host organs and accumulated mainly in tumor
      LP-granules, and (2) decreasing the alpha-tocopherol content of these hypoxic EAC
      cells while no activation of the main cell antioxidative enzymes (GSH-Px, SOD)
      took place. The vitality and high resistance of EAC stationary cells were
      accompanied by the 'paradoxical' state with great differences between the
      resistance of the intracellular PUFA-rich granules and other cytoplasmic
      sections. A similar state was found in stationary ZAH cells. The cell state is in
      good agreement with the Dormandy's suggestion that PUFA-rich granules can trap
      reactive radical species preventing their interaction with 'critical' PUFA
      membranes.

PMID- 7633831
TI  - Adjuvant radiotherapy for breast cancer as a risk factor for the development of
      lung cancer.
AB  - Women diagnosed with primary breast or lung cancer and recorded between 1972 and
      1989 in our tumor registry were identified. Of 4,123 lung cancer patients and
      3,537 breast cancer patients, 42 patients with both diagnoses were identified.
      The two malignancies were diagnosed simultaneously in five patients, lung cancer
      was diagnosed first in six patients and breast cancer was diagnosed first in 31
      (p < 0.001). Nineteen of those 31 patients received adjuvant radiotherapy for
      breast cancer and developed lung cancer a median of 17 years later. Of the 19
      irradiated patients who subsequently developed lung cancer, 15 did so in the
      ipsilateral lung and only four had lung cancer contralateral to the previously
      irradiated site (p < 0.001). Adjuvant radiotherapy for breast cancer as delivered
      decades ago may be an etiologic factor for lung cancer.

PMID- 7633830
TI  - Carboplatin-liposomes (CPL) in immunodeficient mice: improved antitumor activity
      for breast carcinomas and stimulation of hematopoiesis.
AB  - Carboplatin-liposomes (CPL) have been shown to possess a strong stimulatory
      activity on the hematopoiesis in immunocompetent mice. As we were interested in
      studying this pharmacological characteristic in parallel with any antitumour
      effects which might be expected for the encapsulated cytostatic, we used a panel
      of six human breast carcinomas xenotransplanted to nude mice. The antitumor
      activity as well as the hematopoietic effects of the vesicles were studied in
      comparison to, and in combination with, the free drug. Carboplatin was
      encapsulated into reverse phase evaporation vesicles (REV) and injected i.p. as a
      single dose of 75 mg kg-1 into tumor-free and breast-carcinoma-bearing animals,
      respectively. Following a single application of CPL in nude mice, a significant
      increase of the WBC numbers to about three times for that of the normal level
      could be observed over a period of at least 28 days. The elevation was due to an
      increase in both circulating granulocytes and lymphocytes. The peripheral effect
      was accompanied by a relative decrease of spleen cellularity, while the number of
      bone marrow cells was hardly affected. There was no influence detectable on
      circulating blood cells in SCID mice. However, a rather high toxicity of CPL for
      this immunodeficient mouse strain was noticed. In the panel of breast carcinomas
      used, free carboplatin and CPL displayed a different pattern of therapeutic
      efficiencies. In four of the five tumor models tested, a combination of the free
      with the liposomal drug showed a significant inhibition of tumor growth while
      effectively preventing a drug-induced leukopenia.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7633832
TI  - Cytomegalovirus pneumonia prior to engraftment following T-cell depleted bone
      marrow transplantation.
AB  - CMV pneumonia is a frequent complication of allogeneic bone marrow
      transplantation (BMT). It usually appears 23 months following transplantation and
      is associated with a high mortality rate. The incidence of CMV pneumonia in our T
      lymphocyte depleted allogeneic BMT recipients, transplanted between 1987-1991,
      was 18 out of 197 (9.2%) patients. In 3 patients (1.5% of allogenic BMT
      recipients), pneumonia occurred prior to marrow engraftment, on days 12-16 post
      BMT. These patients did not develop acute GVHD in contrast to 9/11 patients who
      had acute GVHD in addition to developing CMV pneumonia between engraftment and
      day +100 (p < 0.03). Furthermore, these three patients did not receive steroid
      therapy as opposed to 14/15 patients who were treated with steroids and
      eventually contracted CMV pneumonia post-engraftment (p < 0.01). The three
      patients did not have two additional risk factors known for the development of
      CMV pneumonia: increasing age and a diagnosis of acute myeloblastic leukemia
      (AML) as the primary disease. Despite prompt diagnosis and therapy with
      ganciclovir and high doses of intravenous immunoglobulin (IVIG), two of the
      patients died. Tcell depleted BMT may be a risk factor for development of CMV
      pneumonia occurring prior to engraftment. In the era of post-BMT anti CMV
      prophylaxis, one should be aware that life-threatening CMV pneumonia may appear
      prior to engraftment and consider aggressive CMV prophylaxis.

PMID- 7633834
TI  - Mitomycin C directly augments the expression of HLA-DR antigen in a gastric
      carcinoma cell line.

PMID- 7633833
TI  - Mafosfamide enhances interleukin-2-generated human effector cell cytotoxic
      activity against K562 myeloid leukaemia cells.

PMID- 7633835
TI  - Involvement of plasma copper, zinc and cadmium in human carcinoma of uterine
      cervix.

PMID- 7633836
TI  - Effects of human papillomavirus type-specific antisense oligonucleotides on
      cervical cancer cells containing papillomavirus type 16.

PMID- 7633838
TI  - [Nilvadipin for nifedipine induced calf edema. Results of a double blind
      randomized comparative study].

PMID- 7633839
TI  - [Early recognition and management of polyneuropathies. Report from the media
      workshop Diagnostic and Therapeutic Recommendations for the Management of
      Polyneuropathies. Hamburg, December 11, 1993].

PMID- 7633840
TI  - [New dimensions in the therapy of chronic polyarthritis. Diagnosis and therapy
      from an immunologic viewpoint. 11th Rheuma conference. Rottach-Egern, 26 November
      1994].

PMID- 7633837
TI  - Neuroblastoma stage IV-S.
AB  - A review of stage IV-S neuroblastoma is provided. The possible uses of prognostic
      features to guide treatment options in this group of infants with neuroblastoma
      are suggested. The biologic basis for the spontaneous regression of widespread
      tumor involvement in some infants with stage IV-S neuroblastoma is discussed. The
      reasons that some infants with IV-S disease progress to a fatal outcome, while
      most undergo maturation or involution and eventual long term cure are suggested.
      The influence of such factors as age at diagnosis, clinical staging, and tumor
      biology on eventual outcome are covered. Biological variables and markers
      discussed include: genetic (cytogenetics (1p deletions), nuclear genomic
      content), molecular biologic (N-myc oncogene amplification, mdr-1, ras, and trk,
      gene expression), immunological (major histocompatibility antigen density,
      cellular and humoral immunity), and biochemical (creatine kinase isoenzyme
      profile, neuron specific enolase, ferritin, chromatograffin, lactic acid
      dehydrogenase and catecholamine levels).

PMID- 7633842
TI  - Role of high-dose therapy with peripheral blood progenitor cell support in
      multiple myeloma.

PMID- 7633841
TI  - Recombinant interleukin-2 treatment before and after autologous stem cell
      transplantation in hematologic malignancies: clinical and immunologic effects.
AB  - Autologous bone marrow transplantation (ABMT) for hematologic malignancies is
      associated with a high relapse rate. Interleukin-2 (IL-2) administration is a
      therapy that may prevent relapse if used when the tumor burden is minimal. In
      this study we administered recombinant IL-2 (rIL-2) therapy to 12 patients
      affected by hematologic malignancies either before or after autologous stem cell
      transplantation (ASCT). rIL-2 was given by a 6 day continuous intravenous
      infusion with escalating doses, up to 18 x 10(6)/m2/day, depending on patient
      tolerance. The functional immune responses of the patients were assessed as
      natural killer (NK) and lymphokine-activated killer (LAK) cytotoxic activities
      and in vitro interferon-gamma (IFN-gamma) and tumor necrosis factor alpha (TNF
      alpha) synthesis. During rIL-2 treatment, the expected side effects occurred;
      only 3 patients, who showed severe cardiovascular toxicity, required suspension
      of the treatment. All toxicities reversed after the end of the therapy.
      Immunologic monitoring was carried out the day before starting rIL-2 infusion and
      then repeated on days 3, 7, and 14 after rIL-2 was discontinued. Following every
      rIL-2 course, a pronounced increase in CD3+, CD8+, CD56+ cells was found, with a
      peak value on day 3. The NK and LAK activities showed a significant increase on
      day 3 (p < 0.001) over pretherapy values; the increase lasted until day 14,
      although the difference at later time points was not significant. Before
      transplant the synthesis of both IFN-gamma and TNF-alpha decreased following rIL
      2 therapy, whereas higher levels of these lymphokines were found after
      posttransplant rIL-2 courses.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7633843
TI  - Metastatic proliferation of meetings.

PMID- 7633844
TI  - Production of genetically modified Epstein-Barr virus-specific cytotoxic T cells
      for adoptive transfer to patients at high risk of EBV-associated
      lymphoproliferative disease.
AB  - EBV-induced lymphoproliferative disease (EBV-LPD) is a disorder most commonly
      associated with the immunocompromise that follows allogeneic organ
      transplantation. In patients receiving T cell-depleted bone marrow from HLA
      mismatched or HLA-matched unrelated donors, the incidence of EBV-LPD is
      particularly high, ranging from 5 to 30%. Administration of EBV-specific
      cytotoxic T lymphocytes may be one means of preventing and treating this disease.
      We now describe a method that allows the routine and timely preparation of large
      numbers of such cells to allow their safe administration to bone marrow
      transplant recipients. We also describe how these cells may be genetically marked
      before infusion, to determine their fate and disposition in vivo.

PMID- 7633845
TI  - Complications of peripheral blood stem cell harvesting: review of 554 PBSC
      leukaphereses.
AB  - The collection of PBSC for transplantation requires repetitive leukapheresis,
      typically via central venous catheters (CVC). To assess the complications of this
      procedure, we reviewed 75 consecutive PBSC transplant candidates requiring 554
      leukapheresis on a Haemonetics V50 Plus apheresis system. CVC occlusion
      necessitating thrombolytic therapy or cancellation of the procedure was the most
      commonly observed complication, occurring among 37 patients on 86 occasions
      (15.9% of CVC-aided collections). Thrombolytic therapy was successful in 85%. Of
      the patients, 16% experienced an infectious complication during the PBSC
      harvesting; chemotherapy mobilization significantly increased this risk, whereas
      growth factor mobilization was protective (p < 0.02). Hematologic complications
      including anemia (median postapheresis nadir hemoglobin 8.8 g/dl) and transient
      thrombocytopenia (median postapheresis nadir 64,000/microliters) required
      transfusional support among 30.7% and 14.7% of patients, respectively. The use of
      chemotherapy mobilization was correlated with increased need for support of both
      red cells and platelets (p < 0.001). Additional complications included catheter
      placement problems, symptomatic citrate-related hypocalcemia, transient
      hypotension, and machine-related malfunctions. Although the complications of the
      PBSC harvests were manageable, given their frequency the decision to pursue this
      form of hematopoietic rescue in preference to traditional operative bone marrow
      harvesting must address these risks.

PMID- 7633846
TI  - Retroviral vector for gene therapy of X-linked severe combined immunodeficiency
      syndrome.
AB  - X-linked severe combined immunodeficiency syndrome (X-SCID) is a genetic disorder
      characterized by profound impairment of cell-mediated and humoral immunity.
      Affected children die of recurrent infections within 2 years of birth unless
      rescued by allogeneic transplantation from a suitable donor. Recently, the
      genetic defect responsible for X-linked SCID has been identified as a mutation in
      the gamma chain of the IL-2 receptor, a protein also shared by the IL-4 and IL-7
      receptors and therefore now denoted the common gamma chain (gamma c). We report
      here the development of a high-titer amphotropic retroviral vector for transfer
      of gamma c. This vector was used to transfer a copy of the gamma c cDNA to murine
      3T3 fibroblasts, CD34-enriched hematopoietic progenitor cells obtained from bone
      marrow and umbilical cord blood of normal donors, and to transplanted murine bone
      marrow progenitors. Murine 3T3 cells transduced by the retroviral vector were
      analyzed by Southern blot hybridization and Western transfer. Southern analysis
      confirmed the integration of unrearranged proviral DNA, and Western blot analysis
      demonstrated the expression of gamma c protein. CD34-enriched cells were infected
      with viral vectors bearing gamma c and grown in methylcellulose media. Individual
      colonies and pools of cells were analyzed 2 weeks later by polymerase chain
      reaction assay, which confirmed the proviral marking. The vector was also used to
      transfer a copy of the gamma c cDNA to murine bone marrow cells in a
      transplantation model. Infected marrow was transplanted into syngeneic Balb/c
      mice.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7633847
TI  - Recombinant human deoxyribonuclease for hematopoietic stem cell processing.
AB  - Numerous reagents are used in the collection processing and storage of
      hematopoietic progenitor cells for transplantation. To decrease potential
      variations in the final component for transplantation, these reagents should be
      uniform in safety, potency, and efficacy. Pharmaceutical-grade reagents are ideal
      but often are not available. Recently, recombinant human deoxyribonuclease
      (DNase) was approved for the treatment of patients suffering from the pulmonary
      complications of cystic fibrosis. We tested this pharmaceutical for toxicity to
      hematopoietic progenitor cells. These cells were exposed to a range of incubation
      concentrations for both the recombinant enzyme and bovine DNase previously used
      in this laboratory. No loss of nucleated cells or hematopoietic progenitors was
      observed after short-term incubation (1 h) or with direct addition to the culture
      medium. No incremental toxicity was observed in using recombinant enzyme with
      murine anti-B cell antibodies and rabbit complement in an immunologic purge
      technique. A variable effect on cell recovery after thawing of cryopreserved bone
      marrow cells was observed for both enzyme sources. These data suggest that the
      pharmaceutical-grade, recombinant human DNase may substitute for previously used
      reagent-grade protein from animal sources.

PMID- 7633849
TI  - Thoracic injuries.
AB  - Thoracic injury is the second leading cause of death in pediatric trauma, second
      only to head injury in lethal potential. With the exception of lung contusion,
      serious injuries to vital thoracic structures are associated with mortality rates
      in excess of 50%. With blunt chest trauma, approximately 15% of the deaths result
      directly from intrathoracic injury, but with penetrating chest trauma, nearly
      100% of the deaths result from intrathoracic injury. Facility with management of
      thoracic injuries is therefore vital to optimal outcome in childhood trauma.

PMID- 7633850
TI  - Controversies in abdominal trauma.
AB  - The treatment of children who have major abdominal injuries has changed
      significantly during the past 2 decades. Surgical restraint has been the theme,
      and increased awareness of anatomic patterns and physiological responses has
      prompted successful nonoperative care of many solid organ injuries in children.
      The contributions of interventional radiologists and endoscopists in the
      treatment of injured children continue to increase. Injuries to the biliary tree
      and pancreatic ductal system are now treated with a multidisciplinary approach
      combining percutaneous, open, and endoscopic procedures. Trauma surgeons
      unfamiliar with a nonoperative approach often raise questions about the benefits
      of such treatment. Their concerns include the potential for increased transfusion
      requirements, increased length of hospital stay, and missed associated injuries;
      some even question the involvement of pediatric surgeons in nonoperative
      treatment protocols. The experience that has settled most such controversies is
      reviewed in this article.

PMID- 7633848
TI  - Diagnostic imaging in pediatric trauma.
AB  - In the management of the critically injured pediatric trauma patient, the
      diagnostic armamentarium of the clinician includes a number of radiographic
      procedures to assist in determining the life-threatening and disabling injuries
      of the young patient. This article reviews the emergent and definitive systems
      radiographs helpful in diagnosing blunt and penetrating injuries. The clinician
      is provided a stepwise systematic process of evaluating life-threatening and
      complicated injuries of the head, thorax, abdomen, pelvis, and extremities.

PMID- 7633852
TI  - The pediatric trauma center.
AB  - The types of facilities providing care to injured children vary greatly. Some
      have organized, planned, and functioning Pediatric Trauma Units with all the
      appropriate personnel, equipment, and facilities needed to provide whatever is
      needed. Other institutions have done no planning, have no trained personnel, and
      are, in short, ill prepared to provide any type of care. The resources needed to
      provide optimum care to the injured child are described for two types of
      facilities--the Regional Pediatric Trauma Center (RPTC), which provides the most
      comprehensive of pediatric trauma services, and the Trauma Center with Pediatric
      Commitment (TCPC), which is the type of institution at which the majority of
      pediatric trauma care is rendered.

PMID- 7633851
TI  - Critical care of the injured child.
AB  - Critical care of the injured child should be an effective extension of aggressive
      resuscitation, stabilization, and definitive care. In the hours and days after
      acute injury, initially unnoticed lesions may emerge, secondary organ dysfunction
      may develop, and complications of primary injury or initial management may occur.
      We approach critical care of the severely injured child as a continuation of care
      begun in the trauma center. We follow an organ system, problem oriented protocol,
      and attempt to anticipate problems before they occur. This article defines our
      approach in general terms, with specific emphasis on the more common problems
      encountered in caring for seriously injured children.

PMID- 7633853
TI  - The immune response to trauma.
AB  - The response to trauma begins in the immune system at the moment of injury. The
      loci are the wound, with activation of macrophages and production of
      proinflammatory mediators, and the microcirculation with activation of
      endothelial cells, blood elements, and a capillary leak. These processes are
      potentiated by ischemia and impaired oxygen delivery and by the presence of
      necrotic tissue, each exacerbating the inflammatory response. Hemorrhage alone
      may be a sufficient stimulus. Inflammation once was considered to be a host
      reaction to bacteria or other irritants. This concept was expanded by the
      discovery of autoimmune diseases, and we are now aware that some illnesses are
      the result of the body's response to an invader rather than the direct effect of
      the invader itself. The discoveries about the response to trauma described here
      add another dimension, showing inflammation to be a fundamental life process that
      begins at the molecular level at the moment of injury and that, depending on the
      severity of the stimulus and the effectiveness of initial treatment, may spread
      to include every cell, tissue, and organ in the body, for good or ill. An
      important part of these expanding concepts is the notion that all noxious stimuli
      activate the cytokine system as a final common pathway. Sepsis, hemorrhage,
      ischemia, ischemia-reperfusion, and soft tissue trauma all share an ability to
      activate macrophages and produce proinflammatory cytokines that may initiate the
      SIRS. Second-message compounds and effector molecules mediate the observed
      clinical phenomena.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7633854
TI  - The real incidence of pediatric trauma.
AB  - Trauma care is one of the major components of modern surgery. This is especially
      true of pediatric surgery, because injuries are by far the leading cause of death
      for children from early childhood through adolescence. Recently, the
      epidemiological model of host, agent, and environment has been applied to the
      study of childhood injuries to increase understanding of their causes and to
      provide a basis for primary and secondary prevention strategies. We now know that
      injury patterns vary with age, sex, race, place of residence, and family income,
      and that the rates of fatal injury from violence, whether interpersonal or self
      inflicted, are increasing. We also know that firearms are involved in an ever
      increasing proportion of cases. As trauma care has improved, the key to further
      reductions in the toll of injuries on our children is prevention.

PMID- 7633855
TI  - Transport of the injured child.
AB  - This article summarizes current recommendations regarding prehospital
      stabilization and transport of the injured child. Transportation alternatives are
      described, as well as indications for interhospital transport. A checklist for
      troubleshooting common problems is included, which anticipates events likely to
      cause morbidity en route. Proper communication is essential to a successful
      transport, as is a quality review of each completed transport. Emergency Medical
      Services for Children (EMSC) grants have enabled many states to enhance pediatric
      prehospital education for providers.

PMID- 7633857
TI  - The Future of Children. A selected bibliography.

PMID- 7633856
TI  - Resuscitation of the injured child.
AB  - Unintentional injury is the leading cause of death for children less than 14
      years of age. Optimal injury control includes prevention, acute care, and
      rehabilitation. When prevention efforts fail, a dedicated well-trained team must
      be prepared to resuscitate and treat the injured child. This article presents an
      approach to resuscitation that emphasizes the primary and secondary survey. Early
      and aggressive airway control with cervical spine protection is stressed,
      followed by a rapid assessment of ventilatory mechanics and circulatory status.
      Clinical indicators of inadequate tissue perfusion are described, with priorities
      concerning intravenous access highlighted. Initial resuscitation steps,
      complemented by laboratory and radiological assessment, occur before the
      secondary survey. The secondary survey completes the early resuscitation phase
      and consists of a systematic and complete physical examination. Resuscitation
      priorities specific to the multiply-injured child are also discussed. Finally,
      the importance of rehabilitation and prevention efforts are included.

PMID- 7633858
TI  - The role of prenatal care in preventing low birth weight.
AB  - Prenatal care has long been endorsed as a means to identify mothers at risk of
      delivering a preterm or growth-retarded infant and to provide an array of
      available medical, nutritional, and educational interventions intended to reduce
      the determinants and incidence of low birth weight and other adverse pregnancy
      conditions and outcomes. Although the general notion that prenatal care is of
      value to both mother and child became widely accepted in this century, the
      empirical evidence supporting the association between prenatal care and reduced
      rates of low birth weight emerged slowly and has been equivocal. Much of the
      controversy over the effectiveness of prenatal care in preventing low birth
      weight stems from difficulties in defining what constitutes prenatal care and
      adequate prenatal care use. While the collective evidence regarding the efficacy
      of prenatal care to prevent low birth weight continues to be mixed, the
      literature indicates that the most likely known targets for prenatal
      interventions to prevent low birth weight rates are (1) psychosocial (aimed at
      smoking); (2) nutritional (aimed at low prepregnancy weight and inadequate weight
      gain); and (3) medical (aimed at general morbidity). System level approaches to
      impact the accessibility and the appropriateness of prenatal health care services
      to entire groups of women and population-wide health promotion, social service,
      and case management approaches may also offer potential benefits. However, data
      on the effectiveness of these services are lacking, and whether interventions
      focused on building cohesive, functional communities can do as much or more to
      improve low birth weight rates as individualized treatments has yet to be
      explored. The ultimate success of prenatal care in substantially reducing current
      low birth weight percentages in the United States may hinge on the development of
      a much broader and more unified conception of prenatal care than currently
      prevails. Recommendations for actions to maximize the impact of prenatal care on
      reducing low birth weight are proposed both for the public and for the
      biomedical, public health, and research communities.

PMID- 7633859
TI  - The role of lifestyle in preventing low birth weight.
AB  - Lifestyle behaviors such as cigarette smoking, weight gain during pregnancy, and
      use of other drugs play an important role in determining fetal growth. The
      relationship between lifestyle risk factors and low birth weight is complex and
      is affected by psychosocial, economic, and biological factors. Cigarette smoking
      is the largest known risk factor for low birth weight. Approximately 20% of all
      low birth weight could be avoided if women did not smoke during pregnancy.
      Reducing heavy use of alcohol and other drugs during pregnancy could also reduce
      the rate of low birth weight births. Pregnancy and the prospect of pregnancy
      provide an important window of opportunity to improve women's health and the
      health of children. The adoption before or during pregnancy of more healthful
      lifestyle behaviors, such as ceasing to smoke, eating an adequate diet and
      gaining enough weight during pregnancy, and ceasing heavy drug use, can
      positively affect the long-term health of women and the health of their infants.
      Detrimental lifestyles can be modified, but successful modification will require
      large-scale societal changes. In the United States, these societal changes should
      include a focus on preventive health, family-centered workplace policies, and
      changes in social norms.

PMID- 7633860
TI  - Evaluation of neonatal intensive care technologies.
AB  - The development and dissemination of neonatal intensive care technology has been
      associated with improved survival for critically ill newborn infants,
      particularly those with birth weights of less than 1,500 grams (3 pounds, 5
      ounces). Despite these advances, there are concerns about the long-term health
      status of surviving infants and the costs of their initial and subsequent care.
      In this article, the authors review current evidence for the effectiveness of
      neonatal intensive care and discuss several approaches to evaluating neonatal
      intensive care technology. They discuss a four-step process originally proposed
      by Roper for assessing and improving neonatal intensive care practices which
      includes (1) monitoring of practices, outcomes, and costs; (2) analysis of
      variation in practices, outcomes, and costs; (3) assessment of the efficacy of
      individual interventions, and (4) feedback and education to alter clinical
      behavior. The authors conclude that organized networks of neonatal intensive care
      units can play a crucial role in this process.

PMID- 7633861
TI  - Access to neonatal intensive care.
AB  - The birth of a high-risk infant is still a relatively rare, not totally
      predictable event; and the management of high-risk newborns requires highly
      skilled personnel and sophisticated technology. In the early days of neonatal
      intensive care, scarce resources led to regionalized systems of neonatal and,
      later, perinatal services, generally based on voluntary agreements but sometimes
      reinforced by planning legislation. At present, a vastly increased pool of
      skilled professionals and technical resources is available in the context of a
      rapidly changing medical care system characterized by intense competition,
      coalescence of services under large managed care plans, and substantial cost
      pressures. The evidence suggests that, in many areas, these forces have led to
      the dismantling of regional networks; however, the full potential for these
      changes to hinder or facilitate access to neonatal intensive care remains to be
      assessed.

PMID- 7633862
TI  - The problem of low birth weight.
AB  - Low birth weight is a major public health problem in the United States,
      contributing substantially both to infant mortality and to childhood handicap.
      The principal determinant of low birth weight in the United States is preterm
      delivery, a phenomenon of largely unknown etiology. Preterm delivery is more
      common in the United States than in many other industrialized nations, and is the
      factor most responsible for the relatively high infant mortality rate in the
      United States. Within the United States, Asian populations experience the lowest
      preterm delivery rates, while Hispanic and Native American populations experience
      slightly higher preterm delivery rates than the white population. African
      Americans, however, have much higher rates of preterm delivery than any of the
      other major ethnic groups. Poverty is strongly and consistently associated with
      low birth weight, but the precise social and environmental conditions that
      produce preterm delivery have not been elucidated. Although it is popular to link
      illicit drug use to low birth weight, a high low birth weight rate was
      characteristic of the United States for decades before the cocaine epidemic of
      the 1980s. Neither the low birth rate nor the preterm delivery rate has improved
      in the United States in the past quarter century. Most efforts to prevent
      prematurity or low birth weight, when carefully evaluated, have not proven
      effective. A major goal of biomedical research ought to be better understanding
      of the causes of this important public health problem.

PMID- 7633864
TI  - Unintentional injuries.

PMID- 7633863
TI  - Evidence-based ethics and the care of premature infants.
AB  - Despite the success of newborn intensive care, a vexing ethical question remains:
      Which preterm infants are so malformed, sick or immature that newborn intensive
      care should not be administered? In an attempt to answer this question, this
      article examines current clinical practices and the persisting effects of the
      controversial Baby Doe regulations. The scientific evidence for current practices
      is critically analyzed in relation to fundamental ethical issues for marginally
      viable patients of any age. A variety of strategies--some highly provocative--is
      proposed and discussed to facilitate better-informed, better-justified, more
      broadly acceptable, and more fiscally responsible ethical decisions in the care
      of preterm infants.

PMID- 7633866
TI  - The direct cost of low birth weight.
AB  - Medical and technological advances in the care of infants with low birth weight
      (less than 2,500 grams, or 5 pounds, 8 ounces) and very low birth weight (less
      than 1,500 grams, or 3 pounds, 5 ounces) have substantially increased the
      survival rate for these infants and have led to concerns about the demands their
      care places upon their families and society. The dollar cost of the resources
      used disproportionately to care for low birth weight children is one measure of
      the burden of low birth weight. Using analyses of national survey data for 1988
      for children ages 0 to 15, this article presents estimates of the direct
      incremental costs of low birth weight--costs of the resources used to care for
      low birth weight infants above and beyond those used for infants of normal birth
      weight. In 1988, health care, education, and child care for the 3.5 to 4 million
      children ages 0 to 15 born low birth weight between $5.5 and $6 billion more than
      they would have if those children had been born normal birth weight. Low birth
      weight accounts for 10% of all health care costs for children, and the
      incremental direct costs of low birth cost weight are of similar magnitude to
      those of unintentional injuries among children and in 1988 were substantially
      greater than the direct costs of AIDS among Americans of all ages in that year.

PMID- 7633865
TI  - State initiatives to provide medical coverage for uninsured children.

PMID- 7633867
TI  - Low birth weight: analysis and recommendations.

PMID- 7633868
TI  - The role of basic science in preventing low birth weight.
AB  - Recent experimental studies in a wide range of animal species have shown that the
      fetus determines the duration of pregnancy. The mechanism by which the birth
      process is initiated is closely linked to the normal maturation of vital fetal
      organs, such as the lungs. Thus, under normal circumstances, the fetus should be
      adequately prepared for the challenges of an independent life after birth. The
      fetal endocrine changes that lead to birth result in increased maternal estrogen
      production and stimulation of effective uterine contractility and dilation of the
      cervix. Preterm delivery can occur as a result of several different pathological
      processes, including infection and various forms of stress. Successful strategies
      for preventing the preterm delivery of low birth weight infants will depend upon
      an improved ability to diagnose which of the many components of the normal birth
      process has been prematurely activated in each pregnant patient undergoing
      premature labor.

PMID- 7633869
TI  - The role of obstetrical medical technology in preventing low birth weight.
AB  - Technology plays an important role in the practice of medicine, and it is
      essential that controlled clinical trials be conducted before new technologies
      are widely disseminated. In this article, information from the medical literature
      is summarized and critiqued for several common obstetric technologies which are
      aimed at reducing the incidence or sequelae of low birth weight and preterm
      birth. These technologies include home uterine activity monitoring, tocolytic
      drugs to suppress uterine contractions, corticosteriods to accelerate fetal lung
      maturity, bed rest to prevent preterm delivery, delivery methods, multifetal
      pregnancy reduction, and cervical cerclage. A major challenge to the practice of
      medicine is to find effective ways to modify physician behavior to encourage the
      use of proven, effective technologies, and discourage the use of unproven,
      ineffective technologies. Despite widespread use, most obstetrical technologies
      appear to have had little impact on reducing the incidence of low birth weight or
      preterm births, as rates of low birth weight and preterm birth have not decreased
      appreciably in the past 25 years. Uncovering the basic mechanisms responsible for
      the onset of preterm labor will undoubtedly facilitate the discovery of new
      technologies to prevent low birth weight and preterm births.

PMID- 7633870
TI  - The role of social change in preventing low birth weight.
AB  - The authors of this article examine the relationship between social factors and
      low birth weight and the ways in which disparities in socioeconomic status have
      been addressed over time. The evidence regarding the effectiveness of various
      efforts to influence birth weight by mitigating the consequences of disadvantage
      are also assessed. Low socioeconomic status has been shown to influence low birth
      weight through its various correlates. Historically and today, most programs and
      policies directed at low birth weight prevention attempt to address the
      individual health consequences of economic and social disadvantage. By and large,
      these efforts have produced mixed results. Efforts to affect low birth weight by
      addressing the underlying causes of social and economic disadvantage have been
      similarly inconclusive, reflecting the paucity of research on the subject, as
      well as the historical and ongoing failure to make the research link between
      health and social policy. The authors argue that reducing persistent disparities
      in low birth weight requires several steps, including embracing a broader
      definition of health which incorporates social dimensions, recasting the focus of
      research and interventions from pregnancy outcomes and infant health exclusively
      to include the notion of women's health more globally, expanding the research
      agenda to unravel the paradox of socioeconomic factors and health, and pursuing a
      dedicated, national commitment to assuring adequate support to individuals and
      families, including both adequate income and health care.

PMID- 7633871
TI  - Irritable bowel syndrome.

PMID- 7633872
TI  - Steroid resistance in asthma.
AB  - Resistance to the anti-inflammatory effects of glucocorticoids in asthma and
      other inflammatory and immune diseases is uncommon, but presents a management
      problem. Understanding the mechanisms of steroid resistance provides new insights
      into the mechanism of steroid action as well as the underlying chronic disease
      process. In patients with primary steroid-resistant (SR) asthma there is no
      abnormality in the pharmacokinetics of the exogenous steroid and no significant
      defect in steroid binding to the glucocorticoid receptor (GR). Recent studies
      have demonstrated a marked reduction in the binding of GR to DNA; this appears to
      be due to increased binding of GR to the transcription factor activator protein-1
      (AP-1). Secondary steroid resistance in asthma may arise in response to the
      release of cytokines that activate AP-1 and other transcription factors that bind
      directly to GR. A similar effect may also be seen with high concentrations of
      beta 2-agonists that activate another GR binding transcription factor, CREB.
      Several existing and novel treatment strategies are possible in the management of
      SR asthma.

PMID- 7633873
TI  - Autres pays, autres coeurs? Dietary patterns, risk factors and ischaemic heart
      disease in Belfast and Toulouse.
AB  - The WHO MONICA project monitors trends and determinants in cardiovascular disease
      to relate classical risk factor changes to trends in incidence rates. The Belfast
      and Toulouse MONICA centres have also collaborated in dietary studies. Both
      centres have validated incidence and attack rates for ischaemic heart disease
      using coronary event registration. These data confirm that the disease in middle
      aged men is between three and four times as common in Belfast as in Toulouse.
      Risk factor surveys show some differences between the centres, but the overall
      risks assessed by two multiple logistic function scoring systems were identical.
      A weighed dietary survey revealed no important difference in macronutrient
      intake, although carbohydrate and saturated fat intake in Belfast was
      significantly higher. Protein, dietary cholesterol and polyunsaturated fat,
      particularly linoleic acid intake, was significantly higher in Toulouse, as was
      consumption of wine, cheese, fruit and vegetables, but not potatoes. The Northern
      Irish diet is typically Northern European, but although the diet in Toulouse has
      some features of the Mediterranean diet, it is not appreciably different from
      that in Belfast in terms of total fat intake. Major differences are present for
      several food items, and in general these differences add support to the
      antioxidant hypothesis.

PMID- 7633874
TI  - The Edinburgh City Hospital cohort: analysis of enrollment, progression and
      mortality by baseline covariates.
AB  - We describe baseline characteristics, enrollment, progression and mortality of
      the Edinburgh City Hospital HIV cohort. There were 431 men and 191 (31%) women;
      439 (71%) infected via injection drug use (IDU); 92 (15%) via homosexual
      intercourse; 84 (13%) via heterosexual intercourse and 7 from blood products.
      Median annual rate of CD4 cell loss was 49 (90% range: 15-146); Both homosexual
      men and patients aged > 40 years at enrollment lost CD4 cells significantly more
      quickly. In multifactorial analysis controlled for baseline CD4 count and IgA,
      there was no gender effect, but young patients (< 25 years) progressed
      significantly more slowly to AIDS (RR 0.4, p = 0.00). Homosexual men progressed
      significantly more quickly than IDUs, with adjusted relative risks (RR) of 2.9 (p
      = 0.00), 2.5 (p = 0.01) and 1.5 (p = 0.1) for progression to CDC stage IV, AIDS
      and death, respectively. The three-year survival rate post-AIDS was 25% (SE 4.3)
      and there was no gender effect on survival. There was, however, an age effect
      whereby individuals diagnosed with AIDS in their 40s or later showed poorer
      survival (RR 1.9, p = 0.04). Zidovudine treatment after an AIDS diagnosis
      significantly lengthened post-AIDS survival (RR 0.5, p = 0.08).

PMID- 7633875
TI  - Long-term treatment of chronic inflammatory demyelinating polyradiculoneuropathy
      with plasma exchange or intravenous immunoglobulin.
AB  - To assess long-term treatment of chronic idiopathic demyelinating
      polyradiculoneuropathy (CIDP) with plasma exchange (PE) and intravenous
      immunoglobulin (IVIg), we studied 105 patients retrospectively by case-notes and
      follow-up. Thirty-three were treated with PE; 23 responded well. Twenty-two were
      treated with IVIg; 14 responded well and one had a hypotensive reaction during
      the first infusion. For both treatments, responders were more likely to be female
      and younger, and to have a shorter duration of symptoms. Most patients required
      only one course of treatment. Seven patients received repeated courses of PE for
      8.1-59.7 months; seven received repeated courses of IVIg for 6-51 months.
      Transient complications occurred with PE: hypotension in three, difficulty in
      gaining venous access in three, and haematoma, bleeding diathesis, hypocalcaemia,
      and septicaemia in one patient each. Four patients transferred from long-term PE
      to IVIg, but the fifth responded to PE only. Two patients who were transferred
      from PE to IVIg were eventually able to stop all treatments. Long-term use of
      IVIg was free of any significant complications. Both PE and IVIg are possible
      long-term treatments for CIDP, but both are expensive, and PE had more side
      effects.

PMID- 7633876
TI  - Smoking habits and lipoproteins in British women.
AB  - The incidence of coronary heart disease is increasing in women. Some of this may
      be related to increased smoking in women over the past decades. However, the
      mechanism mediating the smoking-coronary heart disease link is unclear. We
      therefore assessed the relationship of smoking habits to fasting plasma insulin,
      total and low-density lipoprotein (LDL) cholesterol, triglyceride, high-density
      lipoprotein (HDL) cholesterol, including its subfractions HDL2 and HDL3, body
      mass index, and waist:hip circumference ratio in 1048 women aged 25-69 years.
      Compared with non-smokers, current smokers had higher plasma concentrations of
      LDL cholesterol by 0.2 mmol/l or 6%, total/HDL cholesterol ratio by 0.5 or 13%,
      triglyceride by 0.14 mmol/l or 13% and waist:hip ratio by 0.02 or 3%, but lower
      HDL cholesterol by 0.13 mmol/l or 9% and HDL2 cholesterol by 0.07 mmol/l or 13%,
      while ex-smokers had higher waist hip ratio by 0.01 or 1% but lower HDL
      cholesterol by 0.06 mmol/l or 4% and HDL2 cholesterol by 0.09 mmol/l or 16%. Ex
      smokers for up to 5 years, compared with non-smokers, had higher plasma
      concentrations of total/HDL cholesterol ratio by 0.4 mmol/l or 11%, triglyceride
      by 0.22 mmol/l or 21% and waist hip ratio by 0.01 or 1%, but lower levels of HDL
      cholesterol by 0.12 mmol/l or 9% and HDL2 cholesterol by 0.14 mmol/l or 26%.
      Cigarette smoking is associated with adverse changes in lipoprotein levels; these
      changes decrease slowly after quitting.

PMID- 7633877
TI  - Management of systemic vasculitis: contribution of scintigraphic imaging to
      evaluation of disease activity and classification.
AB  - The use of radio-isotope-labelled leucocyte scans has become established as a non
      invasive and accurate means of diagnosing a variety of inflammatory conditions.
      We report a retrospective study on leucocyte imaging in the management of 50
      patients with systemic vasculitis. Leucocyte imaging was useful for detecting
      unsuspected sites of disease and monitoring disease activity. Scintigraphy was
      superior to conventional radiography or CT scanning for detecting and monitoring
      vasculitic involvement of the respiratory tract. The scans were useful for
      differentiating between Wegener's granulomatosis (WG) and microscopic
      polyangiitis (MPA). There was a close and statistically significant relationship
      between the clinical diagnosis of WG and nasal uptake on leucocyte scans (p <
      0.01), whereas in patients with MPA it was rare. Anti-proteinase 3 autoantibody
      specificity correlated significantly with nasal uptake of labelled leucocytes (p
      < 0.03). Leucocyte imaging is a useful non-invasive investigation in patients
      with systemic vasculitis.

PMID- 7633879
TI  - End-stage renal failure in Indo-Asians.

PMID- 7633880
TI  - Spinal NMDA receptor--nitric oxide mediation of the expression of morphine
      withdrawal symptoms in the rat.
AB  - Previous studies in this laboratory have demonstrated that cholinergic receptors
      within the spinal cord play an important role in the expression of naloxone
      precipitated withdrawal symptoms in the morphine-dependent rat. Related
      cardiovascular studies in non-dependent animals have demonstrated that this
      spinal cholinergic system is linked to a glutamatergic, NMDA pressor pathway
      which also involves the participation of a nitric oxide (NO) generating system.
      The purpose of this study was to determine whether spinal NMDA receptors and/or
      NO are involved in the expression of morphine withdrawal symptoms. Rats bearing
      previously implanted intrathecal (IT) catheters were dependent on morphine
      following chronic i.a. infusion of increasing doses over 5 days. Naloxone (0.5
      mg/kg) was administered via the i.a. line to precipitate withdrawal; and both
      cardiovascular and behavioral symptoms were recorded over 60 min. Pretreatment 20
      min before naloxone with IT injection of either of the NMDA receptor antagonists,
      MK-801 or AP-7 (100-200 nmol), produced a significant reduction in the expression
      of both the cardiovascular and behavioral symptoms of up to about 60%. IT
      pretreatment with the NO synthase inhibitor L-NAME--a methyl ester derivative of
      L-arginine, also produced a dose-dependent, L-arginine reversible inhibition of
      the cardiovascular (mainly the pressor) component of withdrawal, but had no
      significant effect on the expression of behavioral signs. In contrast, IT
      pretreatment with L-NOARG and L-NMMA, non-ester analogs of L-arginine,
      significantly inhibited the expression of the behavioral signs of withdrawal but
      did not alter the pressor component. A combined pretreatment with L-NAME and L
      NOARG resulted in suppression of both pressor and behavioral components of
      withdrawal. The anti-withdrawal actions of either class of NO synthase inhibitor
      could not be attributed to blockade of local muscarinic receptors. These findings
      are consistent with a role for both spinal NMDA receptors and a NO generating
      system in the expression of both the behavioral and autonomic components of
      naloxone-precipitated withdrawal. They also suggest that different structural
      analogs of L-arginine have different profiles of activity in this regard--opening
      the possibility that different isozymes of NO synthase located within the same
      spinal region mediate different physiological or behavioral functions.

PMID- 7633878
TI  - Economics in sample size determination for clinical trials.
AB  - In the design of clinical trials, sample size determination is usually undertaken
      by statisticians and clinicians. It is rare for health economists to be involved
      in this aspect of trial design. However, there are a number of outcome changes
      that are of 'economic significance', and it is important for trial designers and
      funders to be aware of these before planning, funding and mounting a trial. In
      this paper we demonstrate through the use of three examples (prevention of
      osteoporosis, management of infertility, and endometriosis) how economics can be
      used to influence the size of a clinical trial. Trials that are too small or too
      large waste research resources; health economics can lead to more efficient trial
      designs.

PMID- 7633881
TI  - Parvalbumin- and calretinin-immunoreactive trigeminal neurons innervating the rat
      molar tooth pulp.
AB  - Calcium-binding proteins and neuropeptides were examined in trigeminal neuronal
      cell bodies retrogradely labeled with Fast blue (FB) from the maxillary molar
      tooth pulp of the rat. FB-labeled cells were located in the maxillary division of
      the trigeminal ganglion. Approximately 30 and 50% of the labeled cells were
      immunoreactive for parvalbumin and calcitonin gene-related peptide (CGRP),
      respectively. The coexpression of these substances was observed in 9.5% of FB
      labeled cells. On the other hand, 2.4% of FB-labeled cells exhibited calretinin
      immunoreactivity (CR-ir) and 20% tachykinin (TK)-ir. The coexpression of CR and
      TK was observed in 1.9% of FB-labeled cells, i.e., most of CR-ir FB-labeled
      neurons coexpressed TK-ir. An immuno-EM method revealed that all parvalbumin-ir
      nerve fibers in the root pulp were myelinated and that CGRP-ir nerve fibers were
      both myelinated (15%) and unmyelinated (85%). The present study indicated that
      primary nociceptors innervating the rat molar tooth pulp contained parvalbumin
      and CR and coexpressed these calcium-binding proteins and neuropeptides. It was
      suggested that peripheral axons of parvalbumin-ir tooth pulp primary neurons are
      all myelinated. Most peripheral CR-ir axons are probably unmyelinated because TK
      ir myelinated axons have never been demonstrated in any peripheral organ.

PMID- 7633883
TI  - Aversive taste stimuli facilitate extracellular acetylcholine release in the
      insular gustatory cortex of the rat: a microdialysis study.
AB  - The release of extracellular acetylcholine (ACh) in the insular gustatory cortex
      of conscious rats during taste stimulation was measured using the microdialysis
      technique. The mean basal release of ACh before stimulation was 273 +/- 21
      fmol/10 microliters (mean +/- S.E.M., n = 25). Intraorally applied taste stimuli
      or distilled water significantly increased the release of ACh. Among them,
      infusion of 0.001 M quinine HCl produced a marked increase in the release of ACh
      up to 355% of baseline levels. Infusion of 0.01 M saccharin to the subjects that
      had acquired an aversion to this taste also caused a prominent increase in ACh up
      to 343% of basal levels. In contrast, saccharin infusion to the naive subjects
      moderately increased ACh up to 243% of baseline. Water infusion resulted in the
      smallest increase in ACh up to 175% of baseline. Although intraoral infusions of
      quinine or distilled water caused a significant increase in ACh in the parietal
      cortex, the magnitude of increased ACh was smaller than that in the gustatory
      cortex. These results suggest that ACh release in the insular gustatory cortex is
      related to behavioral expression to aversive taste stimuli.

PMID- 7633882
TI  - Long-lasting increase in protein kinase C activity in the hippocampus of amygdala
      kindled rat.
AB  - Previous studies have demonstrated that membrane-associated protein kinase C
      (PKC) activities in the right and left hippocampus of rats kindled from the left
      hippocampus increased significantly at 4 weeks [9] and 4 months [22] after the
      last seizure compared with those in matched control rats. In this study, we
      investigated the effect of kindling from the left amygdala on PKC activities in
      the amygdala/pyriform cortex and hippocampus at long seizure-free intervals (4
      and 16 weeks) from the last amygdala-kindled seizure. Membrane-associated PKC
      activity of the kindled group increased significantly only in the left
      hippocampus compared with the left side control (the left hippocampus of rats
      subjected to a sham operation) at 4 weeks (by 34%, P < 0.03) and 16 weeks (by
      24%, P < 0.05) after the last seizure. There was no significant alteration in the
      membrane-associated PKC activity of the kindled group in the right hippocampus or
      amygdala/pyriform cortex in any seizure-free interval after the last amygdala
      seizure. Cytosolic PKC activity did not differ between the kindled and control
      groups in any brain region examined in any seizure-free interval. At 16 weeks
      after the last seizure, the PKC activity in the P1 fraction of the kindled group
      increased significantly only in the left hippocampus (by 49%, P < 0.005), but not
      in the right hippocampus. Neither PKC activity in the P2 fraction nor that in the
      cytosolic fraction was altered in the kindled group after this seizure-free
      interval.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7633886
TI  - Localization of NADPH-diaphorase in the goldfish brain.
AB  - The distribution of NADPH-diaphorase positive neurons was studied by using the
      enzyme histochemical method. Numerous neurons were labeled in different brain
      areas of the goldfish and their distribution showed some differences in
      comparison with other studied teleosts, indicating a species-specific pattern of
      NADPH-diaphorase distribution as observed in mammals. The localization of NADPH
      diaphorase in the thalamic nuclei, in the paraventricular organ, in the inferior
      hypothalamic lobe, in the periventricular neurons of the optic tectum, in the
      nucleus isthmi and in the mesencephalic reticular formation was comparable to the
      one observed in other teleosts. In addition in the goldfish the telencephalic
      neurons of the pars centralis and lateralis of the area dorsalis, the habenular
      neurons, the bipolar neurons of the central grey layer of the optic tectum and
      the motor neurons of the hypertrophied vagal lobe were labeled. The localization
      of NADPH-diaphorase positive neurons, compared to the distribution of cholinergic
      neurons described in fish, indicated that the production of nitric oxide was
      prevailing in the brain areas where cholinergic circuits are active.

PMID- 7633885
TI  - Mechanisms within the human spinal cord suppress fast reflexes to control the
      movement of the legs.
AB  - Passive locomotor-like movement induces depression of the gain of a fast
      conducting spinal sensorimotor path in humans. It was hypothesized that this gain
      control is mediated through a spinal circuit. In the first experiment, passive
      pedalling motion was rapidly initiated in eight able bodied subjects. Soleus H
      reflexes (used to reveal the gain of the short latency stretch reflex) were
      recorded over the first 250 ms after the movement started. Significant depression
      in H-reflex magnitude was observed by 50 ms after the onset of movement. On the
      basis of the timing, this gain attenuation was likely mediated through a spinal
      circuit. In a second experiment we tested chronic quadriplegics with clinically
      complete lesions of the spinal cord. Of five subjects tested, three expressed the
      reflex and all three showed significant inhibition with passive pedalling
      movement (mean depression was to 39% of controls). Both the rapid onset of the
      gain change (Expt. 1) and the presence of movement-induced inhibition in
      individuals with spinal lesions (Expt. 2) provide evidence that this component of
      human locomotor control is located in the spinal cord. The initiating source is
      probably somatosensory receptor discharge due to the movement.

PMID- 7633884
TI  - In vivo detection of immunoreactive neurokinin A release within rat substantia
      nigra and its dependency on a dopaminergic input.
AB  - In the striatum, the tachykinin peptide neurokinin A (NKA) is thought to coexist
      with substance P in the gamma-aminobutyric acid-containing spiny neurones which
      project to the substantia nigra. We have used in vivo antibody-coated microprobes
      to directly monitor the release of NKA-like immunoreactivity (NKA-LI) within
      substantia nigra during various pharmacological manipulations. The data clearly
      illustrates a basal or resting extracellular presence of NKA-LI restricted to
      substantia nigra reticulata which was found to be largely dependent on a
      dopaminergic input. Acute administration of haloperidol (0.1-0.2 mg/kg i.p.)
      considerably reduced this basal NKA-LI whereas depot administration (14 mg/kg
      i.m. released over 2 weeks) produced a less substantial reduction. Lesion of
      nigro-striatal dopamine neurones with the neurotoxic agent 6-hydroxydopamine
      produced significant reductions in the nigral NKA-LI detected. However, d
      amphetamine administration (4 mg/kg i.p.) did not alter the pattern of NKA-LI
      release for up to 4 h posttreatment. These results indicate that changes in
      peptide mRNA levels do not necessarily reflect changes in peptide release and
      suggest that NKA may be the more physiologically relevant tachykinin within the
      substantia nigra of the rat.

PMID- 7633887
TI  - Inhibition of withdrawal responses by pelvic nerve electrical stimulation.
AB  - In urethane-anesthetized rats, the compound action potential of the pelvic nerve
      was found to consist of three different waves, two in the A delta fiber and one
      in the C-fiber range of conduction velocity. Electrical stimulation of the pelvic
      nerve produced a complete inhibition of the withdrawal response to noxious foot
      pinch or foot compression. The electromyographic (EMG) activity of the
      contralateral posterior biceps muscle was used to record the withdrawal response.
      The withdrawal response inhibition was related to the duration and the frequency
      of electrical stimulation. Low (5-10 Hz) and high (100-300 Hz) frequencies were
      ineffective in inhibiting the withdrawal response, whereas intermediate
      frequencies (20-80 Hz) produced a complete inhibition of the withdrawal response.
      Short (300 ms) trains of stimulation inhibited the withdrawal response only
      during the stimulation period. Longer trains of stimulation (500 ms-10 s)
      produced long-lasting inhibition of the response to noxious stimulation. The
      inhibition persisted for up to 20 s after the end of electrical stimulation of
      the pelvic nerve. A delta fiber stimulation was adequate to inhibit the
      withdrawal response in most (15 out of 17) of the animals. However, A delta plus
      C-fiber stimulation was needed to inhibit the response to noxious stimulation in
      two animals. In addition to inhibiting the response to noxious stimulation,
      pelvic nerve electrical stimulation reflexively activated abdominal muscles. On
      the basis of present findings using electrical stimulation, it can be suggested
      that, in the rat, A delta and C-visceral afferents of the pelvic nerve mediate
      the analgesic effect of vaginocervical probing pelvic and A delta afferents the
      contraction of abdominal muscles in the fetus-expulsion reflex.

PMID- 7633888
TI  - Prevention of macrophage invasion impairs regeneration in nerve grafts.
AB  - The importance of cell invasion for regeneration in nerve segments was
      investigated in rats. The regeneration distance of axons in predegenerated nerve
      segments was compared to the outgrowth in nerve segments where cell invasion had
      been prevented. A 10 mm long nerve segment, which was predegenerated (preserved
      or impaired blood circulation) or kept in a Millipore chamber (pore size 0.22
      microns), was sutured as a nerve graft at the contralateral side three days or
      two weeks after the initial procedure. At two weeks immunocytochemical staining
      and routine histologic analysis revealed pronounced myelin breakdown and presence
      of ED1 and ED2 positive macrophages in the predegenerated nerve segment. Nerve
      segments, which were kept in the Millipore chamber, showed no invasion of
      macrophages and the myelin sheaths were preserved. The regeneration distances of
      axons in the nerve segments, evaluated with the pinch reflex test, were
      significantly longer in the predegenerated nerve segments compared to the nerve
      segments kept in Millipore chambers. Nerve grafts, which were taken from
      predegenerated nerves with intact blood circulation, showed the longest
      regeneration distances. It is suggested that the regeneration process can be
      impaired in nerve segments where cell and macrophage invasion as well as myelin
      breakdown are prevented and that preservation of the blood circulation during the
      degeneration process is important.

PMID- 7633889
TI  - PKA activity in the antennal lobe of honeybees is regulated by chemosensory
      stimulation in vivo.
AB  - The involvement of cyclic nucleotide cascades has been suggested for chemosensory
      signal processing as well as synaptic plasticity. Cyclic AMP-dependent protein
      kinase (PKA) is a major mediator for transient changes in these second
      messengers. The objective of this study was to examine the role of PKA in the
      central processing of chemosensory information by the honeybee. Effects of
      chemosensory stimulation in vivo were detected in the first chemosensory neuropil
      of the honeybee brain, the antennal lobe (AL), by using a combination of shock
      freezing and specific determination of PKA activity. Mechanosensory or odor
      stimulation of the antennae had no effect on PKA activity. Brief application of
      aqueous solutions (pure water or sucrose solution) to an antenna caused a rapid
      and transient elevation of PKA activity in the ipsilateral AL. A series of such
      stimuli led to a graded increase in PKA activity followed by a rapid decrease
      during the first 10 s after the end of stimulation, but elevated levels of PKA
      activity were observed for as long as 1 min. These results suggest that PKA
      activity and its regulation contribute to central processing of chemosensory
      signals.

PMID- 7633890
TI  - Complex changes of GABAA and GABAB receptor binding in the spinal cord dorsal
      horn following peripheral inflammation or neurectomy.
AB  - Chronic peripheral inflammation or peripheral neurectomy cause changes in GABA
      levels and GABA immunoreactivity in the spinal cord dorsal horn. The present
      study aimed to investigate if such changes are accompanied by alterations in GABA
      receptor binding. Neurectomy of the sciatic nerve caused an ipsilateral down
      regulation of GABAB receptor binding in lamina II of the spinal cord 2-4 weeks
      after the nerve injury. Since approximately 50% of GABAB receptor binding in that
      region is located on primary afferent endings, degenerative changes of such
      endings caused by the nerve lesion can explain the observed reduction. In
      contrast, GABAA binding was substantially enhanced following neurectomy, which
      may be due to an up-regulation of the receptors issued by the concomitant
      decrease of endogenous GABA. In rats bearing unilateral chronic peripheral
      inflammation induced by intraarticular injection of complete Freund's adjuvant we
      found a reduction of GABAB binding in the superficial dorsal horn. This effect,
      which was maximal at 3-4 weeks after adjuvant injection, was attributed to an
      enhanced release of GABA by spinal interneurons. GABAA receptor binding was not
      changed in this experimental model. Together, these results suggest that the two
      receptor types may be located at different loci and are differently affected by
      variations in sensory input.

PMID- 7633891
TI  - Vasopressin and oxytocin gene expression in intact rats and under catecholamine
      deficiency during ontogenesis.
AB  - The development of the hypothalamic vasopressin (VP) and oxytocin (OT) systems
      has been studied in rats from the 16th embryonic day (E16) until the 11th
      postnatal day (P11). The VP and OT mRNA-producing neurons were identified on
      cryostat sections by in situ hybridization using oligonucleotide probes labeled
      by [35S], [3H] or digoxigenin. Moreover, VP and OT gene expressions were
      evaluated either at E21 or at P11 following chronic depletion of catecholamines
      (CA). For this purpose, pregnant rats were daily injected with alpha-methyl-m(p)
      tyrosine from gestational day 13 to 20 while neonates were daily injected with
      alpha-methyl-m(p)-tyrosine and neurotoxin 6-hydroxydopamine from postnatal day 2
      to 10. No VP mRNA- or OT mRNA-expressing cells were observed in the hypothalamus
      of intact fetuses at E16, while 2 days later rather numerous VP and OT neurons
      occupied the anterior hypothalamus. One major bilateral group of VP and OT
      neurons was located in the supraoptic nucleus (SON). Less numerous labeled cells
      were found in the developing paraventricular nucleus (PVN). Some VP and OT
      neurons were also spread along the ventrolateral surface of the hypothalamus from
      the level of the median eminence, caudally, to the level of the optic nerves,
      rostrally. From E18 until birth, the OT neurons were localized in the dorsal
      portion of the SON, while its ventral portion was occupied by the VP neurons. The
      VP mRNA- and OT mRNA-expressing cells seemed to increase both in size and in
      number over the perinatal period. Frequent relatively long neuronal processes
      contained VP and OT mRNAs in fetuses and in newborns. When performed during the
      second half of the fetal life, the chronic depletion of CA did not cause any
      change in the VP and OT mRNA concentrations in the SON and PVN of fetuses. By
      contrast, similar treatment of neonates resulted in a significant increase of
      both mRNA levels in the SON. These data suggest that at least in the SON VP and
      OT gene expression might be under the inhibitory control of CA during the
      neonatal period.

PMID- 7633892
TI  - Immunoreactivity for beta/A4 protein, but not for its precursor, in human
      chromaffin cells.
AB  - The present study was designed to establish a) whether chromaffin cells of the
      human adrenal medulla express immunoreactivity for beta-amyloid precursor protein
      (beta APP) and/or beta-amyloid protein (beta/A4); and b) whether cells expressing
      one or both of the above-mentioned proteins display immunoreactivity for the low-
      (gp75) and/or the high-affinity (gp140-trkA) nerve growth factor receptor. To
      identify chromaffin cells and their supporting cells, chromogranin A,
      neurofilament proteins, and S-100 protein were studied in parallel. Beta APP and
      beta/A4 immunoreactivity (IR) was observed primarily labeling two different cell
      populations, without colocalization: Beta APP IR was found in the adrenal
      cortical cells, which were mainly localized in the reticulate layer and in the
      blood vessel walls, whereas beta/A4 IR was observed in the chromaffin cells.
      Furthermore, supporting cells were also immunoreactive for beta/A4, and
      sympathetic ganglionic cells were immunoreactive for both beta APP and beta/A4.
      Interestingly, clusters of cells expressing beta/A4 IR also displayed gp 75 IR
      and/or gp140-trkA IR. Finally, all chromaffin cells (identified by chromogranin A
      IR) were immunolabeled for the 200 kDa neurofilament subunit, but not for a
      phosphorylated epitope of this protein. These results demonstrate the occurrence
      of beta/A4 IR, but not of beta APP, in the chromaffin cells of the human adrenal
      gland. The complementary distribution of amyloid-related proteins, and the
      possible involvement of neurotrophins in beta/A4 metabolism are discussed.

PMID- 7633893
TI  - Evidence against a hemodynamic role for serotonin in the dorsal motor nucleus of
      the vagus.
AB  - This study was performed to investigate the potential role of serotonin (5-HT) in
      the dorsal motor nucleus of the vagus (dmnX) in regulating peripheral
      hemodynamics. Microinjections (5 or 25 nmol in 50 nl) of the monoaminergic
      neurotransmitter were made into the dorsomedial medulla of the
      urethaneanesthetized rat during continuous recording of femoral arterial blood
      pressure. Heart rate was extracted electronically from the pressure waveform.
      Discrete injections of 5-HT placed directly in the dmnX were found to be entirely
      without effect on peripheral hemodynamics. In contrast, injections placed in the
      solitary tract nucleus, lying immediately above the dmnX, were found to have
      profound depressor and bradycardic effects, while the immediately subjacent
      hypoglossal nucleus appeared to contain both depressor and unresponsive sites.
      These findings cast doubt on the involvement of serotonin in the dmnX in the
      regulation of cardiovascular hemodynamics.

PMID- 7633894
TI  - Role of cholinergic and adrenergic pathways of the medial septal area in the
      water intake and pressor response to central angiotensin II and carbachol in
      rats.
AB  - In the present study, we investigated the effect of previous injection of either
      prazosin (alpha 1-adrenergic antagonist) or atropine (muscarinic cholinergic
      antagonist) into the medial septal area (MSA) on the pressor and dipsogenic
      response induced by intracerebroventricular (ICV) injection of carbachol
      (cholinergic agonist) and angiotensin II (ANGII) in rats. The pressor and
      dipsogenic responses to ICV carbachol (7 nmol) were reduced after previous
      treatment of the MSA with atropine (0.5 to 5 nmol), but not prazosin (20 and 40
      nmol). The dipsogenic response to ICA ANGII (25 ng) was reduced after prazosin
      (40 nmol) into the MSA. The pressor response to ICV ANGII was not changed either
      by previous treatment of the MSA with prazosin or atropine. The present results
      suggest a dissociation among the pathways subserving the control of dipsogenic
      and pressor responses to central cholinergic or angiotensinergic activation.

PMID- 7633895
TI  - Temporal modulation of antinociception by reciprocal connections between the
      dorsomedial medulla and parabrachial region.
AB  - Microinjection of carbachol into the dorsal parabrachial regio (PBRd) of guinea
      pigs induces analgesia from the 5th to the 15th min postinjection, as evaluated
      by the reduction of the vocalization in response to an electric shock applied to
      one paw. When reversible blockade of the dorsomedial medulla or specifically of
      the nucleus tractus solitarius (NTS) is performed with xylocaine 5 min after
      microinjection of carbachol into the PBRd, the analgesic effect continues up to
      the 45th and to the 60th min, respectively. Blockade of the dorsomedial medulla
      is achieved by topical application of xylocaine to the area postrema (AP) or
      microinjection of the drug into the NTS. A prolongation of the duration of the
      analgesic effect also occurs after the inverse procedure, i.e., after reversible
      blockade of the PBRd 5 min after topical application of carbachol (1
      microgram/microliter)to the AP or microinjection of carbachol into the NTS. In
      this case, the analgesic action, which lasted up to 30 min when carbachol was
      applied to the AP and 60 min when microinjected into the NTS, was prolonged up to
      60 min and to 80 min, respectively, after reversible blockade of PBR. The present
      data suggest that the reciprocal connections between the different regions of the
      dorsomedial medulla and the PBR play an important role in the modulation of the
      duration of the analgesic effect, and that this fact may be of adaptive
      importance in the defensive analgesia that occurs in the confrontation between
      prey and predator.

PMID- 7633897
TI  - Immunolocalization of putative neurotransmitters innervating autonomic regulating
      neurons (correction of neurones) of cat ventral medulla.
AB  - This study investigated possible sites of contact of nerve fibers containing a
      range of putative neurotransmitter substances onto neurons in the cat ventral
      medulla oblongata concerned with autonomic, particularly cardiovascular,
      regulation. The parasympathetic preganglionic neurons of the nucleus ambiguous
      (correction of ambiguus) were identified by retrograde horseradish peroxidase
      tracing from the vagus nerve, and the groups of neurons in the A1 and C1 cell
      areas and the raphe nucleus by catecholamine enzyme or 5-hydroxytryptamine (5-HT)
      immunohistochemistry, respectively. Immunoreactive (-ir)nerve fibers and
      terminals in the vicinity if these neurons were visualized by subjecting the
      sections to a dual-staining technique using a brown peroxidase-diaminobenzidine
      reaction product and a blue alkaline phosphatase-Fast blue reaction product. By
      employing monochrome photography with combinations of blue and orange-red
      filters, it was possible to discriminate neural elements displaying one or the
      other reaction product, or colocalization of reaction products. The results
      revealed the presence of calcitonin gene-related peptide (CGRP) and galanin (GAL)
      ir in some motoneurons of the nucleus ambiguus, but not in those innervating the
      heart via the cardiac vagus nerve. The latter group of parasympathetic efferent
      neurons were found to be densely innervated by fibers immunoreactive for dopamine
      beta-hydroxylase (DBH, indicating noradrenaline), glycine (GLY), gamma
      aminobutyric acid (GABA), 5-HT, enkephalin (ENK), neuropeptide Y (NPY), substance
      P (SP), and thyrotropin-releasing hormone (TRH), and, to a lesser extent, by
      other neuropeptide-ir fibers. The catecholamine cells of the rostral C1 and
      caudal A1 groups showed a broadly similar pattern of innervation, most noticeably
      by fibers immunoreactive for DBH, GABA, 5-HT, cholecystokinin (CCK), CGRP, ENK,
      GAL, NPY, and SP. The 5-HT-ir neurons of the raphe nucleus, some also containing
      SP, TRH, ENK, or corticotropin-releasing factor (CRF)-ir, were most prominently
      innervated by terminals containing DBH, GABA, CCK, ENK, NPY, TRH, somatostatin
      (SRIF), and vasoactive intestinal polypeptide (VIP)-ir. Although the proof that
      these groups of neurons receive functional synaptic contacts from the
      immunoreactive fibers awaits further ultrastructural studies, the results do
      suggest that a wide range of putative transmitters may influence the activity of
      efferent neurons in the cat medulla controlling autonomic functions.

PMID- 7633898
TI  - Nucleus basalis of Meynert cell responses in awake monkeys.
AB  - Extracellular cell activity was recorded in the intermediate and posterior
      subdivisions of the nucleus basalis of Meynert (NBM) of awake monkeys to
      determine cell characteristics and the motor and sensory participation. Animals
      were trained to move a lever by elbow flexion-extensions to receive a reward.
      Cell activity was recorded when the animal was at rest and executing the task.
      The electromyogram of the upper limb, contralateral to the recording site, was
      recorded simultaneously with NBM neuron activity. The effect of visual, auditory,
      and tactile stimuli were also studied after performance of the learned task. A
      moderate number of cells responded to the reward (16%), while a higher percentage
      of them was associated with unexpected, unspecific stimuli (22%). Firing rates
      correlated positively with limb movement (30%). Visual (34%) and auditory (15%)
      responses were also found. No NBM cell responded to tactile stimulation.
      Considering these findings and the anatomical projections over the cortex, the
      NBM role ion complex integrative processes in discussed.

PMID- 7633896
TI  - Electrophysiology of ventromedial striatal neurons during movement.
AB  - The firing rate of ventromedial striatal cells was studied in rats trained to run
      in place on a rotating turntable treadmill. Animals were trained to run clockwise
      and counter-clockwise as they propelled a turntable for a water reward. After a
      period of training, Parylene C coated stainless steel wire electrodes were
      chronically implanted for single unit recording. Nearly all ventromedial striatal
      cells increased their firing rate concomitant with locomotion in the treadmill
      (32 of 36 cells). The magnitude of this response was influenced by the order of
      testing and by the direction of circling relative to the side of brain being
      recorded. The increase in firing rate was greater during the first test of the
      day and was greater when animals circled contralateral to the side of the
      recording electrode than when they circled ipsilateral to the recorded side.

PMID- 7633899
TI  - Blockade of L-glutamate receptors in the rostral ventrolateral medulla
      contributes to ethanol-evoked impairment of baroreflexes in conscious rats.
AB  - This study investigated the effect of ethanol microinjected into the rostral
      ventrolateral medulla on the cardiovascular responses to intrarostral
      ventrolateral medulla administration of the excitatory amino acids L-glutamate
      and N-methyl-D-aspartate (NMDA) and on baroreflex-mediated heart rate responses
      (baroreflex sensitivity) in conscious freely moving Sprague-Dawley rats. L
      Glutamate (5 nmol) or NMDA (25, 50, and 100 pmol) microinjected into the rostral
      ventrolateral medulla elicited pressor and bradycardiac responses. The
      cardiovascular responses elicited by both L-glutamate and NMDA were significantly
      (p < 0.05) attenuated by intrarostral ventrolateral medulla ethanol (10
      micrograms) or 2-amino-5-phosphonopentanoic (2 nmol), a selective NMDA receptor
      antagonist, but not by ACSF. Enhancement of the cardiovascular responses to L
      glutamate by intrarostral ventrolateral medulla p-chloromercuriphenylsulfonic
      acid (0.1 nmol), a glutamate uptake inhibitor, was reversed by subsequent
      ethanol, but not ACSF, microinjection. None of the treatments influenced baseline
      blood pressure or heart rate. Ethanol or 2-amino-5-phosphonopentanoic acid
      microinjected into the rostral ventrolateral medulla significantly (p < 0.05)
      attenuated baroreflex sensitivity tested by phenylephrine. In contrast, p
      chloromercuriphenylsulfonic acid significantly (p < 0.05) enhanced baroreflex
      sensitivity (-2.14 +/- 0.09 vs. -3.08 +/- 0.18); subsequent ethanol
      microinjection reversed this enhancement (-2.90 +/- 0.21 vs. -1.86 +/- 0.24).
      Equal volume of ACSF had no effect on baroreflex sensitivity of pretreated rats (
      3.22 +/- 0.31 vs. -2.98 +/- 0.34). These results suggest that ethanol exerts a
      marked inhibitory action on glutamatergic pathways within the rostral
      ventrolateral medulla that act to enhance baroreflex sensitivity.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7633900
TI  - Short-term cocaine self administration alters striatal gene expression.
AB  - Rats self-administered cocaine or received saline during 3 daily 5 h sessions and
      were euthanized 1 h after the final session. Quantitative in situ hybridization
      revealed that cocaine self-administration increased levels of preprodynorphin,
      but not preproenkephalin, c-fos, or zif/268 mRNAs in a patchy pattern in the
      dorsal striatum. These data demonstrate that the regulation of preprodynorphin
      gene expression is dissociable from that of c-fos and zif/268 in dorsal striatum
      following short-term cocaine self-administration.

PMID- 7633901
TI  - Differential effects of angiotensin II on the activities of suprachiasmatic
      neurons in rat brain slices.
AB  - The effects of angiotensin II (AII) on the firing rates of suprachiasmatic
      neurons were determined in rat brain slices. AII in pmol ranges stimulated 25%
      and inhibited another 25% of 52 irregular firing neurons, while it stimulated 23%
      and inhibited 4% of 30 regular firing neurons. Three "oscillating" neurons whose
      firing rates oscillated with rather constant amplitudes and periods were
      recorded. AII induced the occurrence of oscillation in one unit and modulated the
      oscillation amplitude of the other two. Pretreatment with saralasin, an AII
      antagonist, effectively blocked (100%) the actions of AII (n = 5). The present
      findings suggest that AII may act as an important mediator in the suprachiasmatic
      nucleus and its mode of action may be variable in different neurons.

PMID- 7633902
TI  - Diabetes impairs DRG neuronal attachment to extracellular matrix proteins in
      vitro.
AB  - Attachments of dorsal root ganglion (DRG) neurons from streptozotocin (STZ)
      induced diabetic and normal C57BL mice to the following substrates were evaluated
      in vitro: a) poly L-lysine (PL), b) PL + type I collagen (CL-I), c) PL + type IV
      collagen (CL-IV), d) PL + laminin (LM) and e) PL + fibronectin (FN). After 6 h in
      culture, there was no significant difference in the average ratio of cells
      adhesive to PL between the diabetic (74.9%) and normal group of mice (75.6%). In
      the normal group, the addition of extracellular matrix (ECM) proteins such as CL
      I, CL-IV, LM and FN to PL increased the ratios of cell attachment from 75.6% to
      nearly 90%. In the diabetic group, however, none of these proteins improved the
      attachment (the ratio changed from 74.9% to nearly 70%). Survival and neurite
      extension of attached cells after 48 h in culture were not different between the
      two groups. These results suggest that the cell-surface receptors, which enable
      DRG neurons to bind to the extracellular matrix proteins, are impaired by
      diabetes, resulting in being one of the causes of diabetic neuropathy.

PMID- 7633903
TI  - Contribution of NMDA and nonNMDA glutamate receptors to synchronized excitation
      and cortical output in the primary motor cortex of the rat.
AB  - Application of a GABA (gamma-aminobutyric acid) type A receptor antagonist
      through a microdialysis probe into the forelimb primary motor cortex (MI) of
      ketamine anesthetized rats induced the appearance of paroxysmal field potentials
      recorded in the supragranular layers of the MI and concomitant electromyographic
      (EMG) activity in the contralateral forelimb. Application of a nonNMDA (N-methyl
      D-aspartate) glutamate receptor antagonist in conjunction with the GABA type A
      receptor antagonist completely blocked the paroxysmal field potentials and the
      EMG activity of the contralateral forelimb, while a NMDA receptor antagonist had
      no effect. The results indicate that the spread of activity within the primary
      motor cortex and the motor cortex output are mediated by nonNMDA receptors.

PMID- 7633904
TI  - Effect of decerebration on blood pressure during paradoxical sleep in cats.
AB  - We investigated the effects of decerebration on long-term variations in arterial
      blood pressure during paradoxical sleep (PS) in cats. In normal cats, the blood
      pressure decreased during the transition from slow wave sleep to PS and
      maintained its lower level throughout PS for several days after surgery. After
      this early postoperative stage, however, the arterial hypotension was replaced by
      tonic and phasic rises in blood pressure during PS. Such long-term changes in
      blood pressure were completely abolished when the brain stem was transected at
      the ponto-mesencephalic junction, and the cats consistently exhibited a sustained
      fall in blood pressure throughout the survival periods of 1 month or more.

PMID- 7633905
TI  - A miniaturized cuff electrode for electrical stimulation of peripheral nerves in
      the freely moving rat.
AB  - A bipolar cuff electrode for electrical stimulation of small diameter peripheral
      nerves is described. The cuff is made of a highly flexible rubber-impression
      material, and the electrode assembly is suited for chronic implantation. Its
      manual construction is easy and reliable, utilizing only simple tools. The cuff
      completely envelopes nerves of varying diameter and requires a minimal amount of
      manipulations of the nerve, thereby reducing the chance of surgical trauma. The
      snug envelope prevents the nerve from drying, and minimizes shunting between the
      two leads by extracellular fluids. Small outer dimensions were achieved: 1.4 x
      1.1 x 2.3 mm (width x height x length) when used with nerves of 1 mm diameter,
      which minimizes pressure and damage to surrounding tissues. Morphometric analysis
      of nerves enclosed in cuffs for 28-30 h revealed a small decrease in the number
      of large-diameter fibers. Stimulation thresholds remained, however, constant
      throughout the experiments.

PMID- 7633906
TI  - [Free oxygen radicals in atherosclerosis and diabetes mellitus].
AB  - Recent research suggests that reactive oxygen species (including free radicals)
      may be involved in the initiation and development of vascular complication in
      diabetics. Free radicals meet many of the criteria required for a role in the
      pathogenesis of diabetic vascular disease: they are present in tissues affected
      by the diabetic process, they have a direct toxic effect on tissues, under
      certain condition glucose molecules can induce free radicals production. Diabetes
      mellitus represents a state of increased oxidative stress which is based on
      evidence of increased peroxidation, glycoxidation and reduced antioxidant
      reserve. Glycative stress can be modified by reducing glycemia, maintaining good
      diabetic control, and identifying the patients in whom diabetes or impaired
      glucose tolerance has not been diagnosed. Strategies for reducing the oxidative
      stress may include the supplementation of antioxidant micronutrients (vitamins E
      and C, beta-carotene). At present the most appropriate dose, form, method and
      site of administration of antioxidants are not known. One interesting therapeutic
      approach for the future will be to make apo-B particles more resistant to
      oxidative modification or to reduce the prooxidant activity in general.

PMID- 7633907
TI  - [Endoscopic ultrasonography in the gastrointestinal tract].
AB  - Endoscopic ultrasonography is a combination of endoscopy and ultrasonography.
      This method facilitates an accurate evaluation of singular layers of the gut
      walls and adjacent structures. Great gain is represented by the possibility to
      analyze submucosal tumors, to diagnose vascular anomalies and especially the
      staging of both gastrointestinal malignancies and tumors in the pancreato-biliary
      area. The method is also suitable for the monitoring of treatment of these
      malignancies (chemotherapy, radiotherapy and laser therapy) as well as for an
      early diagnosis of tumor recurrences. The paper enumerates the possibilities,
      limits, some differential-diagnostic problems, complications, as well as
      perspectives of this modern method.

PMID- 7633908
TI  - [Clinical utilization of late ventricular potentials].
AB  - The risk of ventricular arrhythmias may recently be analyzed by late ventricular
      potentials (LVP). The presented paper reviews the pathophysiology of LVP. The
      author describes some methodological and technical problems of LVP registration
      and examination in clinical practice. The main aim of the paper is to bring some
      information on clinical usefulness of LVP. The situations, when the examination
      of LVP is accepted diagnostic method is presented. The author concludes, that
      examination of LVP is highly informative, non-invasive, economically acceptable
      and available from clinical practical point of view. It is helpful for
      stratification of cardiological patients who need more intensive diagnostics and
      therapy.

PMID- 7633909
TI  - [Cardiologic management in patients on a long-term dialysis program].
AB  - Cardiovascular complications are the main cause of mortality in patients with
      chronic renal failure. Hypertension and lipid abnormalities which often lead to
      left ventricular hypertrophy and accelerated atherosclerosis as well as coronary
      artery disease are a common cause of death. On the other hand uremia often causes
      pericarditis and thereby may lead to cardiac tamponade and constrictive
      pericarditis. Renal failure can also cause secondary hyperparathyroidism,
      amyloidosis, hemosiderosis and oxalosis which can produce visceral infiltrations
      and lead to a variety of disturbances of cardiovascular functions. Life
      threatening arrhythmias are one of the major cardiovascular complications during
      maintenance dialysis as their occurrence might result in sudden death. The aim of
      cardiologic management which includes the complex of preventive and therapeutic
      measures is to reduce the morbidity and mortality and to improve the quality of
      life.

PMID- 7633910
TI  - [Scientific and professional publications or informative non-reviewed articles?
      Thoughts at the beginning of 1995].

PMID- 7633911
TI  - [The basis of non-receptor effects of drugs and biologically active substances].
AB  - Most of the cationic amphiphilic drugs (CAD) exert their pharmacological effect
      through specific receptors which are of protein origin. These interactions result
      from a sufficiently tight and time dependent binding of CAD to the cell surface
      transmitting chemical signals into biological effects. For such events each cell
      is equipped with a wide variety of second messengers. Yet the chemical structure
      of CAD and biophysical composition of biological membranes enable interactions
      with corresponding structures without primarily activating the receptor. As a
      rule such interactions bring about a response characterised as side effect of the
      individual drug, which might not be equal to the adverse reaction. Nevertheless,
      these interactions may result also in adverse and toxic responses to the drugs
      administered. The nonreceptor interactions between CAD, cells, tissues, organs
      and the whole organism depend on the physico-chemical nature of these drugs and
      their ability to enter and pass through the plasma membrane on the one side, and
      on the biological properties of membrane phospholipids and their integral
      components, on the other. The structure, synthesis, turnover and metabolism of
      membrane phospholipids play an important role in these processes. Along with A2
      and C phospholipases, membrane phospholipids are also donators of the most
      important second messengers participating in the control of cell functions, such
      as signal transmission, contraction and relaxation of muscles, cell aggregation,
      secretion, phagocytosis. CAD are capable to initiate a biological response
      bypassing specific receptors, interfering thus with the functional structure of
      membrane phospholipids. This effect is time-dependent and dose-dependent and
      besides the above mentioned changes in cell functions, CAD can initiate induction
      of phospholipidoses and nonspecific toxic effects. Further detailed experimental
      and clinical studies are required to provide full understanding of the
      interactions between CAD and changes induced in the lipid, protein and
      carbohydrate cell structures of individual cells and tissues.

PMID- 7633912
TI  - [What is the value of clinical symptoms in the diagnosis of nonspecific
      inflammatory bowel disease?].
AB  - Due to controversial evaluation of the contribution of clinical signs for the
      diagnosing of non-specific inflammatory bowel disease, as well as due to the lack
      of similar data, we tried to find our own answer to the question as to whether
      the clinical signs of ulcerative colitis (UC) and Crohn's disease (MC) are
      helpful, unhelpful, or even confusing for the diagnosis. A group of patients with
      MC and UC was analyzed from this aspect. Individuals in their twenties and
      thirties prevailed in the sample, mostly intellectual workers, the number of
      males and females was equal. Our attempt to analyze all the available diagnostic
      methods originated in an observation that a long period of health problems
      precedes the diagnosis of MC, namely 1.5 y in males and as long as 4 y in
      females. Other striking information was that surgery represented the initial
      treatment in 66% of cases and the correct diagnosis was made peroperatively only
      in 56% of cases. We compared our results with those of the OMGE study, one of the
      largest projects which evaluated positively the contribution of clinical signs to
      the diagnosing of MC and UC. We found that the main signs of CU have not changed
      in the last century, and some additional signs occur rather due to complications
      than due to the disease per se. Frequency of pain increased by 25% in our
      patients, and approximately 1/3 of it represented intermittent pain caused by
      tenesms. Pain in MC must be properly analyzed in order to discriminate acute
      appendicitis. Other indicators did not differ from the OMGE study. In accordance
      with its results, we confirmed the importance of correct evaluation of clinical
      signs for the diagnosis and differential diagnosis of UC and MC. The number of
      diagnostic methods still increases. Their validity must be continuously re
      evaluated, however the clinical examination in the dynamic process stays to be of
      crucial value.

PMID- 7633913
TI  - [Single-dose therapy of infections of the lower urinary tract].
AB  - The authors analyze two clinical studies in the frame of single-dose treatment of
      uncomplicated infection of the lower urinary tract. The first study deals with
      comparison of the effect of netilmicin, ciprofloxacine and aztreonam. The second
      study deals with pefloxacine and cefuroxim-axetil. As the results implied, both
      long-term and short-term effectiveness of therapy comparable with other verified
      regimes was accomplished in female patients who were not pregnant and
      irrespective of their age. It is necessary to respect the contraindications of
      therapy. Chemotherapeutics which are appropriate for single-dose therapy of
      uncomplicated infections of the lower urinary duct include quinolones
      (pefloxacine, ciprofloxacine), phosphomycin-trometamol, co-trimoxozole a
      netilmicin. The majority of oral beta-lactam antibiotics cannot be recommended
      for a single-dose therapy of uroinfections. The authors summarize the advantages
      of a single-dose therapy of uroinfections and analyze the criteria of significant
      bacteriuria.

PMID- 7633914
TI  - [Problems with the limitations of medicine].
AB  - BACKGROUND: Dissatisfaction with the exclusively biomedical approach to the
      etiology, manifestations, treatment and prevention of disease has manifested
      itself by the broadening of the limits of medicine from the inside in the form of
      bio-psycho-social model of diseases. From the outside, there has been an effort
      to enter medicine by various approaches and methods of the so-called alternative
      medicine. OBJECTIVES: Critical evaluation of positives and negatives of the bio
      psycho-social model diseases as well as of the approaches of alternative
      medicine. Particular attention is paid to the so-called psychotronics and
      psychotronics-based natural medicine. METHODS: Analysis of the problem under
      study using world wide publications that are cited in the Current Contents in the
      part dealing with Life Sciences. MAIN RESULTS: Multi-factorial bio-psycho-social
      model of diseases has stimulated the complex interdisciplinary and
      multidisciplinary research of the influence of psychological and psychosocial
      factors upon the human health and diseases respectively. There is, however, a
      lack of concrete directions for the application of the model in clinical
      practice. The main disadvantage of alternative medicine is that its methods have
      no scientifically based conceptions and their effects remain unproved. The main
      risk of the use of these methods are faulty diagnoses and the neglect of the most
      effective treatment. CONCLUSIONS: Medicine is not merely a science, it is an art
      as well. The indispensable part of this are should reside in the most effective
      use of the non-specific positive effects of the interaction between physicians
      and patients.

PMID- 7633915
TI  - Paracrine modulation of coronary vasomotor tone and myocardial performance by
      vascular and endocardial endothelium.
AB  - Over the last years it has become evident that endothelium is one of the most
      active paracrine organs releasing a number of vasoactive substances. These
      mediators, by acting on subjacent vascular smooth muscle, play and important role
      in control of vasomotor tone and of platelets aggregation. The relations between
      vascular endothelium and cardiovascular risk factors are complex. Functional
      abnormalities of vascular endothelium are probably segmental and may differ in
      individual cases. Experimental and clinical study has demonstrated that all
      cardiac endothelial cells, coronary vascular and endocardial, modulate the
      performance of underlying myocardium. Modulation of the left ventricular function
      by endothelial cells constitutes an important autoregulation of muscle-pump
      performance of the heart by altering the duration of contraction and diastolic
      function. It is likely that cardiac endothelial cells take part in extrinsic and
      intrinsic cardiac compensatory mechanisms and, although there is still no direct
      evidence, they may be closely involved in pathophysiology of heart failure in
      humans.

PMID- 7633916
TI  - [Analysis of risk factors for perioperative myocardial infarct in aortocoronary
      bypass].
AB  - BACKGROUND: Perioperative myocardial infarction (PMI) belongs to the main
      complications of revascularization surgery of the heart. Perioperative analysis
      of PIM risk factors can aid the cardiosurgeons, anestesiologists and
      cardiologists to stratify the group exposed to the risk of PIM origin and to
      prepare the most appropriate complex peroperative procedure for this group of
      patients. AIM: The particular aim is to evaluate and analyze some PIM risk
      factors prior to and during surgery. METHODS: The paper represents a
      retrospective study which analyzes two period (1984-1986 and 1992). The total
      number of patients in the investigated group is 277. The group afflicted with PIM
      is constituted of 29 patients. The following clinical, hemodynamic, angiographic
      risk factors are analyzed prior to surgery: age, sex, precedence of infarction of
      myocardium, arterial hypertension, instabile angina pectoris, end-diastolic
      pressure and left ventricular ejection fraction, affliction of the main trunk of
      the left coronary artery and some peroperattive factors (number of grafts,
      sequence bypass, endarterectomy, completion of revascularization, a. mammaria
      interna graft, duration of the artificial vascular circuit and clamping of the
      aorta). RESULTS: Significant relation for the pIM origin was found in arterial
      hypertension (p<0.05), affliction of the main trunk (p<0.05), prolonged period of
      clamping of the aorta (p<0.05 in 1984-86, p<0.01 in 1992) and artificial vascular
      circuit (p<0.001). CONCLUSION: The basic PIM risk factors include the following:
      arterial hypertension prior to surgery, affliction of the main trunk of the left
      coronary artery, prolonged duration of the artificial vascular circuit and
      clamping of the aorta. MEANING FOR PRACTICE: 1. The analyzed problem represents a
      positive feedback for cardiosurgeons, anestesiologists and cardiologists. 2. The
      analysis of the risk factors can be utilized also by future surgical workplaces
      in the Slovak Republic.

PMID- 7633917
TI  - [Personal experience with determination of endogenous, digoxin-like substances in
      patients with myocardial infarct and other cardiopathies].
AB  - A group of 65 patients with acute infarction of myocardium (IM) who were not
      treated with digitalis preparations were subdued to examination to the presence
      of digitalis-like substances in their urine by means of radioimmuno-analytic
      method with use of anti-digoxin antibodies. The control group was constituted of
      69 healthy subjects. Patients afflicted with IM had significantly increased
      concentrations of DLS in serum in comparison with health subjects. No significant
      relations of DLS to the activity of creatinkinase, IM localisation, occurrence of
      dysrhythmias, heart insufficiency and IM mortality were discovered. An increase
      in DLS in the blood of patients with acute IM probably coincides with a decreased
      cardiac output, with the activation of the stress axis and retention of sodium
      and fluids. The second examined group of patients was constituted of 20 subjects
      with other severe cardiopathies (inborn and acquired heart defects, chronic
      ischemic heart disease, inflammatory and degenerative diseases of the heart, and
      hypertension), who were subdued to catheter examinations. The authors discovered
      no significant differences of DLS concentrations in the blood during
      catheterization of individual compartments of inferior vena cava, superior vena
      cava, and the right ventricle. They were not successful in defining the
      particular site of DLS secretion on the basis of this examination. The authors
      pay attention to interaction of DLS during the radioimmuno-analytic examination
      of the digoxin serum concentration.

PMID- 7633918
TI  - [Radiofrequency catheter ablation of atrial tachycardia].
AB  - BACKGROUND AND OBJECTIVE: Radiofrequency catheter ablation has proved to be
      highly effective for the treatment of supraventricular tachycardia originating in
      the AV node or related to atrioventricular accessory pathways. However,
      experience with ablation of atrial tachycardia is more limited. The purpose of
      our study was to analyse the success and safety of radiofrequency ablation of
      atrial tachycardias. STUDY POPULATION: Ten symptomatic patients with drug
      refractory atrial tachycardia. Symptoms included palpitations, dizziness, chest
      pains, shortness of breath, syncope. Five patients had reduced left ventricular
      ejection fraction (tachycardiomyopathy). METHODS: Radiofrequency device -
      Medtronic ATAKRR with temperature monitoring. Temperature ranges from 50 degrees
      C to 70 degrees C were considered optimal to ablation. Ablation catheter - 7 F
      CardiorhythmR with a 4 mm2 deflectable tip. Heparin was given intravenously
      during the procedure (5000 IU bolus + 1000 IU/h). Acetylsalicylic acid 160 mg/day
      for 1 month after the procedure. Antiarrhythmic drugs were discontinued after the
      procedure. The sites for ablation were defined during tachycardia by the earliest
      endocardial atrial activation as compared to the onset of the surface P wave.
      Criteria of success: Abolition of the tachycardia followed by the inability to
      reinduce the tachycardia. FOLLOW-UP: Clinical, ECG and 2D ECHO evaluation in the
      outpatient's clinic. No complications occurred during the procedure. No
      reccurrences of the tachycardia were observed during the follow-up. All 5
      patients with reduced ejection fraction before ablation had normal left
      ventricular function during follow-up. CONCLUSION: Radiofrequency catheter
      ablation is a safe and effective treatment for drug refractory atrial
      tachycardia.

PMID- 7633919
TI  - [The present and future problems of resistance in staphylococci, streptococci and
      M. tuberculosis].
AB  - Mechanisms of resistance of strains of Staphylococcus aureus, Staphylococcus
      epidermidis, Streptococcus pneumoniae, Enterococcus faecalis, Enterococcus
      faecium, Neisseria meningitidis and Mycobacterium tuberculosis to antibiotics are
      presented and discussed. The resistance to methicillin-oxacillin in S. aureus and
      S. epidermidis is chromosomally-mediated by sequence of DNA, namely by gene mecA.
      This gene codes altered PBP-2A protein. Strains of S.pneumoniae contain PBP-1A,
      PBP-2B and PBP-2X proteins. They cause resistance to many beta-lactam
      antibiotics. Resistance to vankomycin, respectively to teikoplanin in strains of
      E. faecalis and E. faecium is coded by transferable vanA and vanB genes. Strains
      of N. meningitidis produce mostly the altered PBP-2 protein. The increase of
      resistance in strains of M. tuberculosis is also significant.

PMID- 7633920
TI  - [Treatment of acute myocardial infarct].
AB  - On the basis of the development of therapeutical procedures in acute myocardial
      infarction (AIM) the author offers the current standpoint to the standard
      medicamentous therapy of this disease. As AIM is caused by thrombotic occlusion
      of the coronary artery, the main therapeutical position is ascribed to the
      thrombolytic therapy. An important position is ascribed to acetylsalicylic acid
      and betablockers. The optimal application is intravenous administration at an
      early stage of the disease. The ISIS-4 study displayed a beneficial impact on
      mortality including ACE inhibitors. The symptomatic therapy includes analgetics
      administered at an early stage of the disease, nitrates and magnesium.
      Antiarrhythmics are not to be applied in a routine pattern. Cardiogenic shock can
      be treated exclusively by invasive therapeutical intervention (e.g. direct PTCA
      or emergent bypass).

PMID- 7633921
TI  - [Lyme borreliosis--diagnosis, clinical aspects and therapy of the cutaneous
      form].
AB  - Occurrence of Lyme borreliosis and namely its skin forms have a rising tendency.
      Thick population of ticks and their relatively high contamination with borrelia
      (app. 9% in Slovakia), increased presence of man in nature and frequent
      professional exposition create good conditions for the spreading of the disease.
      During the period of 20 months in 1993-1994 19 cases of borreliosis were recorded
      among 2,187 patients hospitalized at the Bratislava Dermatologic Clinic--17 cases
      of erythema chronicum migrans and two cases of acrodermatitis chronica
      atrophicans. All patients stated that they came into contact with ticks 24 hours-
      12 months prior to the origin of dermatologic alterations. 14 cases of erythema
      chronicum migrans being IFT examined by means of B. burgdorferi antigen included
      10 patients who yielded the titre of antibodies higher than 1:256; 6 patients
      being examined by means of ELISA test included 2 positive findings. The IFT
      values varied also in cases of classical clinical picture of erythema chronicum
      migrans and a discrepancy was observed between IFT and ELISA results. Two cases
      of acrodermatitis chronica atrophica had positive serologic test. The serologic
      tests were performed also in 4 cases of scleroderma with positive results. Into
      their analysis the authors included also other studies on the basis of which they
      present schemes of diagnostic examination and therapeutic interventions in Lyme
      borreliosis. (Tab. 2, Ref. 4.)

PMID- 7633922
TI  - [Mycotic infections in childhood].
AB  - The occurrence of mycotic infections has a rising tendency. Epidemiologic studies
      investigate this problem in adults. The problem is still insufficiently analyzed
      in children. The study is aimed at gaining information about the occurrence of
      mycoses evoked by dermatophytes and yeasts in children living in Slovakia, namely
      on the basis of the analysis of results for the mycological laboratory. From 1992
      to 1993 6,511 samples which included 556 samples from children were processed on
      the basis of suspective dermatophytoses, the children being at the age of 1 to 15
      years. 6,896 samples suspective of yeast infections included 3,620 mycologically
      positive samples. 279 samples were taken from 265 children at the age of 3 months
      to 15 years. 556 children with dermatophytosis included 116 mycologically
      positive cases, 64 boys and 52 girls. Microscopic examination was positive in 90
      children and cultivation examination was positive in 85 children. Trichophytosis
      was confirmed in 38 children (32.8%) microsporiasis in 9 (7.8%), epidermophytosis
      in 50 (43.1%) and onychomycosis in 19 children (16.3%). Isolated antropophilic
      dermatophytes were represented most frequently by Trichophyton rubrum, 26 times,
      isolated zoophylic species included T. verrucosum, 15 times and T. mentagrophytes
      var. granulosum 13 times. 29 children (25%) had epidermophytosis and
      onychomycosis of feet. The group of 265 children with yeast infections included
      123 with primary skin disease and 134 with internal disease. The most frequently
      monitored materials were stools, 147 times, and scrapings of the oral cavity, 78
      times. The total number of isolated species of yeasts was 17. Candida albicans
      was isolated 218 times (78.2%). The total number of examinations included 7.1
      8.5% of samples from children.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7633924
TI  - [Psoriasis vulgaris and its relation to atopy].
AB  - Psoriasis vulgaris and atopic dermatitis are considered as frequent dermatoses.
      There are descriptions of possible combination of both diseases when patients
      with psoriasis vulgaris display signs of atopy or clinical manifestations of
      atopic dermatitis. We have analysed 9 patients with psoriasis vulgaris and
      increased levels of IgE. In each case we have found signs of atopy and in one
      patient also clinical manifestation of atopic dermatitis. Other most frequent
      immunological markers were represented by increased levels of FW, IgA and C3
      component of complement. The combination of psoriasis vulgaris and atopy is
      possible in one patient but there are many unsolved questions as to the
      conclusion whether such a case represents a random coincidence or association of
      both disease. (tab. 1, Ref. 14.)

PMID- 7633925
TI  - [Study of malignant melanoma using 1H-nuclear magnetic resonance spectroscopy].
AB  - 1H-nuclear magnetic resonance spectroscopy was used to study malignant melanoma
      extract. The aim of this work was to study low molecular weight metabolites
      soluble in water, which can be helpful for a more detailed understanding of tumor
      metabolism with a view to using this knowledge for diagnosis. The authors found
      in a well distinguished spectrum the presence of numerous low molecular weight
      metabolites such as glutamate, glutamine, choline, inositol, creatine,
      phosphocreatine, phosphocholine, glucose, acetate, alanine, lactate. It is
      necessary to correlate these in-vitro findings with a study of the above
      mentioned metabolites in-vivo. Malignant melanoma is appropriate for this
      investigative and diagnostic technique because of its superficial localization.
      (Fig. 1, Ref. 18.)

PMID- 7633923
TI  - [Sclerotherapy of vascular ectasias of the lower extremities].
AB  - The authors treated a group of 138 female patients with injection solutions of
      Aethoxysklerol Fy Kreussler (SRN). They performed both the direct method of
      sclerotherapy by intravascular administration of the concentrations of 0.5 and
      1%, and indirect method of sclerotherapy by intracutaneous administration of the
      concentration of 0.5%. The majority of patients were treated by both methods in
      the presented concentrations. The intravascular method has proved to be the most
      effective. This method yielded a very good homogenous result without recurrences
      in the site of sclerotization. The intracutaneous method yielded a less
      homogenous result and the recurrences occurred most frequently in the site of
      sclerotization in the focus. The therapeutic effect was evaluated after 1 year.
      After this period a good therapeutic effect was achieved in 57.97% out of 138
      patients. In the third year a good therapeutical effect was achieved in 46.77%
      out of 62 patients. In the fifth year a good therapeutical effect was achieved in
      50% out of 14 patients. Three patients were treated for the period of 10 years
      with a satisfactory effect. Significant side effects included focal
      hyperpigmentation of the skin (12 times), urticarial allergic reactions (3
      times), and necrosis of the skin in two cases. Sclerotization of vascular
      cutaneous ectasies by means of the preparation Aethoxysklerol Fy Kreussler (SRN)
      is an appropriate and effective supplementary cosmetologic therapeutic method.
      (Tab. 1, Ref. 20.)

PMID- 7633926
TI  - [The effect of methotrexate on activity of T-lymphocyte marker enzymes in
      patients with psoriasis vulgaris].
AB  - Radiochromatographic methods were used in order to ascertain the activity of
      adenosinedeaminase and purinnucleoside phosphorylase in lymphocytes isolated from
      the venous blood of 32 patients with psoriasis vulgaris in comparison with enzyme
      activities in 28 clinically healthy subjects. 11 selected patients with a severe
      form of psoriasis were subdued to therapy by means of methotrexate and its effect
      on the activity of these enzymes was investigated. Untreated patients yielded a
      statistically significant increase in the activities of adenosinedeaminase and
      purinnucleoside phosphorylase in comparison to the control group of healthy
      subjects. The increase rate of enzymatic activities abruptly reflexed the degree
      of affliction and spreading of the pathological process. Methotrexate
      significantly decreased the activity of both investigated enzymes in lymphocytes
      in patients with psoriasis. On the basis of the achieved results it is possible
      to justify the therapy of psoriasis by means of drugs which influence the
      metabolism of purines and at the same time they interfere the function of T
      lymphocytes.

PMID- 7633928
TI  - [Alopecia areata--an autoimmune disorder?].
AB  - The authors indicated examinations of actual immune states in 42 patients with
      alopecia areata in whom no cause of the disease was stated. The examination
      revealed a deficit in the cellular component of immunity and an increased level
      of immunoglobulin M and C3 component of complement. The examination of these
      patients included also the direct immunofluorescence examination of a skin
      excision from the alopetic focus. Out of 43 examined patients 30 had positive
      immunocomplex findings. Immunocomplexes were most frequently constituted of M
      immunoglobulin, C3 component of complement, as well as of A and G
      immunoglobulins. Immunocomplexes were localized in the lower and sometimes in the
      medium part of the folicle or perifolicullary, the intensity of fluorescence
      depended on the severeness of the disease. The deficit in the cellular component
      of immunity, dysimmunoglobulinemia in the peripheral blood and a positive
      immunocomplex findings in hair folicles at the examination of skin excisions from
      the alopetic focus by means of direct immunofluorescent method enables to include
      the disease of alopecia areata among autoimmune disease. The conclusion deals
      with the possibilities of utilization of local and general immunomodulation
      therapy. (Tab. 2, Fig. 1, Ref. 20.)

PMID- 7633929
TI  - [Pathologic interpretation and clinical aspects of invasive basalioma].
AB  - Bioptic evaluations of basaliomas require from pathologists to perform
      histogenetic classification, type ascertainment, TNM system classification, as
      well as detection of the presence or absence of tumor elements on the margins and
      base of excisions. The systems of histologic type classification of basaliomas
      utilized by pathologists are inconsistent with the terminology used by
      clinicians. The presented work is aimed at correlation of the current terminology
      of invasive basaliomas from the view of dermatologists and pathologists. The
      method of retrospective study was used, namely in a 100 cases of histologically
      verified basaliomas followed by comparisons with clinical diagnoses and
      catamnestic data. Average age in male patients was 66.4 year, and 67.6 year in
      female patients. 11 cases of histologically ascertained types of basaliomas
      included two cases of invasive biological characteristics detected at control
      examinations after 3 months, while the margins and base of the former excisions
      were without tumor elements. In none of the 9 cases of clinically judged invasive
      basaliomas the histologic picture yielded signs of tumor invasiveness. The
      results imply that the clinical diagnosis of a variant of basalioma may represent
      information of its presupposed characteristics. An important task of a
      pathologist is however to notify by means of accurate ascertainment of the
      histologic variant in cases of morpheaphorm and fibroepithelial basalioma the
      possible invasive character of the particular tumor. (Tab. 4, Ref. 14.)

PMID- 7633927
TI  - [Treatment of mycotic skin infections].
AB  - Mycotic infections of the skin remain still to represent a therapeutic problem.
      The development of new antimycotics widens the possibilities of therapy. One of
      them is oxiconasolnitrate which is a derivate of of imadazole. It is available on
      our market as Myfungar cream. The clinical postregistration study verified the
      effectivity of this preperation. The examined group was constituted of 30
      patients. 24 patients were afflicted with epidermophytia inguinalis, 1 patient
      with epidermophytia cruris, 1 patient with epidermophytia manuum, 1 patient with
      trichophytia corporis and 2 with candidosis submammaris. Cultivation examination
      revealed 20 time Trichophyton rubrum, one time Trichophyton mentagrophytes var.
      interdigitale, one time Trichophyton mentagrophytes var. granulosum, one time
      Epidermophyton floccosum, and 2 time Candida albicans. Therapy lasted 21-42 days.
      All patients were treated for a period of 6 weeks. 24 treated cases after the
      therapy included 10 wit persistent squamming, 4 cases with erythema, 3 cases with
      infiltration, and 1 case with persistent vesiculation. 4 patients suffered from
      itch irritation, and 1 from pain. 4 patients were not evaluated for their therapy
      was interrupted. Cultivation examinations in 5 cases revealed the presence of T.
      rubrum. Microscopic examinations were positive in 10 patients. Following 6 weeks
      of therapy 20% of patients remained to yield positive cultivation findings and
      40% of patients were microscopically positive. 2 patients with candidosis were
      clinically cured and their laboratory findings were negative in 5-6 weeks.
      Myfungar creme is a preparation which had in 80% of patients a ver y good or good
      therapeutic effect. Its low sensibilization abilities and application once per
      day are advantageous. (tab. 6, Ref. 6.)

PMID- 7633931
TI  - [Immunostimulation therapy in patients with alopecia areata].
AB  - The authors recorded decreased values of active and total E rosettes and
      increased values of IgM and C3 components of complement in 13 patients with
      alopecia areata. Direct immunofluorescence examination of skin excisions from the
      alopetic foci revealed immunocomplexes in hair follicles. On the basis of these
      examinations, excluding other causes of the disease of alopecia areata, the
      authors indicated the general immunostimulation therapy. (Decabris tbl., Transfer
      faktor inj.). This therapy resulted in an increase in active and total E rosettes
      and a decrease in IgM, and thus in the recovery of cellular and indirectly in the
      humoral component of immunity in the peripheral blood under the circumstances of
      a favourable clinical therapeutic effect.

PMID- 7633932
TI  - [Treatment of chlamydia infections and a brief review of the problems].
AB  - The authors treated 35 patients (17 males, 18 females) with chlamydial infection
      of the urogenital system by means of azithromycin dosed 1.0 g for the first day,
      500 mg from the second till the fifth day of treatment with 82.9% effectivity.

PMID- 7633933
TI  - [Results of mycologic examinations of sputum in patients with pulmonary diseases
      during a 10-year period (1984-1993)].
AB  - The study of present results of mycologic examinations of samples of sputums
      taken during the period from 1984 to 1993 from patients with pulmonary diseases.
      The examined group was constituted of 2,452 subjects, out of which 2/3 were male
      and 1/3 were female patients. The risk age category was discovered to be that
      over 61 years of age (32%). 70% of mycologic cultivations were positive. 1.640
      etiologic agents were isolated from the positive samples. The most frequently
      isolated yeast species were Candida albicans (61.7%), Candida tropicalis (8.2%),
      Torulopsis sp. (4.9%), the most frequent fibrous microscopic fungi findings
      included Penicillium sp. (4.5%) and Aspergillus sp. (2.9%). The most frequent
      diagnoses included bronchitis ac. chr. 15%), pneumonia 13%, TBC of the lungs
      11.7%, asthma bronchiale 10.6%, and bronchopneumonia 7%. Repeatedly C. albicans
      was the most frequently isolated species, namely in the range 52-80%.

PMID- 7633930
TI  - [Morphologic study of mastocytes from skin biopsies in patients with non-systemic
      and systemic mastocytosis].
AB  - The authors describe morphologic changes in mastocytes in the picture of
      transmission electron microscopy (TEM) and skin changes in patients with
      urticaria pigmentosa (7 causes) and systemic mastocytosis (2 causes). The
      presented study analyzes the changes in the cellular membrane and cytoplasmic
      processes, intracytoplasmic membrane structures, mitochondria, granules, and
      nuclei of mastocytes in patients with systemic mastocytosis. The authors evaluate
      these cells as being atypical, respectively immature. The study discusses the
      malignization of these states. (Tab. 2, Fig. 8, Ref. 16.)

PMID- 7633934
TI  - [History of the founding and development of the Dermato-venereology Clinic in
      Bratislava].

PMID- 7633935
TI  - Repeatability of replicate breath alcohol measurements collected in short time
      intervals.
AB  - The effect of short time interval sampling between replicate breath alcohol
      samples has been investigated. The results from 10 samples, which were collected
      approximately one minute apart from eight individuals and approximately 20
      seconds apart from one individual, were evaluated by simple linear regression.
      The regression coefficient (slope) and its standard error were evaluated for the
      presence of any trend in alcohol depletion. Other statistical analyses were also
      included in this assessment. All nine subjects had linear regression coefficients
      for the end-expiratory results that were not significantly different from zero (P
      > 0.05). In view of the respiratory physiology, there does not appear to be any
      measurable depletion of breath alcohol concentration due to sampling intervals as
      short as one minute.

PMID- 7633936
TI  - Prior convictions of child molesters.
AB  - Both the stereotypes held by investigating officers and the clinical literature
      assume that child molesters have distinct characteristics. these are generally
      expected to be reflected in a prior offence history of assaults on children and
      sexually deviant behaviour. A further assumption is that there is an escalation
      of offending, less serious crimes being precursors to more serious ones. To test
      these assumptions the criminal convictions, if any, prior to the offence were
      examined for all 416 detected offenders who had committed sexual offences upon
      children aged between 5 and 12 years, in the Lancashire Police area, during 1987,
      1988 and 1989. Of the 183 (44%) of offenders who had previous convictions, 72
      involved indecency, 17% of the total sample. Only 9 (2%) of offenders had an
      exclusive conviction history in respect of indecency. Previous convictions for
      theft, burglary and violence were all much more frequent. The results also do not
      generally support the hypothesis that serious offenders have progressed from less
      serious offences against children. A criminal opportunist model is proposed as of
      more value for guiding investigations than the existing stereotypes.

PMID- 7633937
TI  - The Journal of Molecular Medicine: tradition, continuity, and renaissance.

PMID- 7633939
TI  - Nitric oxide production by mononuclear leukocytes in alcoholic cirrhosis.
AB  - Nitric oxide is now established as a biological mediator of clinical relevance.
      The present study investigated the production of nitric oxide by lympho
      mononuclear leukocytes from alcoholic patients with either hepatitis or
      cirrhosis. The study included 42 patients, 12 without any liver disease and 30
      alcoholic patients, 13 of whom had histologically confirmed cirrhosis and 17
      alcoholic hepatitis. Cells were obtained from peripheral blood by density
      gradient and incubated in sterile conditions in RPMI 1640 for 6 h at 37 degrees
      C. Culture supernatants were assayed for nitrite concentration using the Griess
      reaction. Cells from cirrhotic but not from hepatopathic patients showed
      significantly higher nitrite production than controls (cirrhotic, 0.36 +/- 0.07;
      hepatopathic, 0.13 +/- 0.02; control: 0.25 +/- 0.05 nmol/10(6) cells/6 h). In
      cirrhotic patients L-Nitro-arginine methylester inhibited nitrite production
      (0.18 +/- 0.05). These data suggest that alcoholic cirrhotic but nonhepatopathic
      patients show an increased nitric oxide production by blood lymphomononuclear
      cells. This production could be involved in the systemic vasodilation in
      cirrhotic patients.

PMID- 7633940
TI  - C1840-T mutation in the human skeletal muscle ryanodine receptor gene: frequency
      in northern German families susceptible to malignant hyperthermia and the
      relationship to in vitro contracture response.
AB  - In swine, a point mutation in the ryanodine receptor gene can account for all
      cases of malignant hyperthermia (MH). The frequency of a corresponding mutation
      in humans (C1840-T) and its relationship to the in vitro contracture profile is
      unknown. We screened 192 patients from 28 unrelated northern German families for
      the C1840-T mutation in the human ryanodine receptor gene and tested for MH
      susceptibility using the in vitro contracture test (IVCT) according to the
      European MH Protocol. In our patients 106 revealed MH susceptible (MHS), 56 MH
      nonsusceptible and 30 MH equivocal status following IVCT. In each family one or
      two individuals had developed clinical signs of MH or a MH crisis. All of these
      patients were classified MHS. The C1840-T mutation was found in 2 of 28 families
      (7.1%). All eight individuals of the two families characterized by this mutation
      revealed MHS status following IVCT. The thresholds for halothane- and caffeine
      induced contractures as well as the contracture profiles following cumulative
      (0.4-10.0 mumol/l every 3 min) and bolus (10 mumol/l) administration of ryanodine
      were found to be similar in MHS patients with and without the C1840-T mutation.
      In conclusion, the C1840-T mutation in the human ryanodine receptor gene is a
      rare abnormality in MHS families. Similar contracture profiles in the presence
      and absence of this mutation might imply no major functional role with respect to
      the contracture response. At present, molecular genetic analysis cannot replace
      IVCT to discover MH susceptibility in humans.

PMID- 7633938
TI  - Immunoprinting: various genes are associated with increased risk to develop
      rheumatoid arthritis in different groups of adult patients.
AB  - To identify genes that contribute to the manifestation of rheumatoid arthritis we
      performed association studies via microsatellite analyses of immunorelevant loci
      (HLA-DRB, 5 T cell receptor loci, TNFa IL1, IL2, IL5R and CD40L). A total of 183
      patients and 275 healthy controls were typed in terms of HLA and grouped
      according to the known predisposing HLA-DRB1 genes (DRB1*04; relative risk
      approx. 5; DRB1*01, relative risk approx. 2; a third group carried neither
      allele). Microsatellite polymorphisms characterizing the TCRBV6S3, CD3D, IL1A,
      IL2, and IL5R genes did not show significant associations with rheumatoid
      arthritis, whereas TCRBV6S1, TCRBV6S7, TNFa, and CD40L genes may influence
      relative protection or risk in certain groups of patients. Analysis of a
      microsatellite marker adjacent to the transcription element alpha (TEA) in the T
      cell receptor alpha delta complex indicates that in the cohort carrying neither
      the DRB1*04 nor the DRB1*01 allele the relative risk to acquire rheumatoid
      arthritis is increased (> 13) or decreased (< 0.07), depending on the inherited
      microsatellite allele adjacent to the TEA locus. Sequence analysis of the closely
      linked TEA region from patients and controls revealed a novel dimorphism. Only
      the newly identified TEA allele leads to binding of a nuclear protein that may be
      involved in the regulated expression of the TCRDA genes. Subsequent typing of
      rheumatoid arthritis patients and controls revealed, however, that the
      association of the microsatellite marker is largely independent of the TEA
      allele, confirming incomplete linkage in the 2 kb region of the TCRDA locus.
      These results are discussed in the context of hot spots of recombination in this
      genomic region and other linked candidate sequences that predispose to develop
      rheumatoid arthritis.

PMID- 7633941
TI  - Apolipoprotein(a) phenotypes and lipoprotein(a) concentrations in patients with
      hyperthyroidism.
AB  - Lipoprotein(a) [Lp(a)] is a low-density lipoprotein (LDL) particle in which
      apolipoprotein B-100 (apoB) is attached to a glycoprotein called
      apolipoprotein(a) [apo(a)]. Apo(a) has several genetically determined phenotypes
      differing in molecular weight, to which Lp(a) concentrations in plasma are
      inversely correlated. High plasma levels of Lp(a) are associated with
      atherosclerotic diseases. It is therefore of interest to study whether factors
      other than the apo(a) gene locus are involved in the regulation of Lp(a)
      concentrations. We measured plasma concentrations of Lp(a) and other lipoproteins
      and determined apo(a) phenotypes in 31 patients with hyperthyroidism, before and
      after the patients had become euthyroid by treatment. The mean concentration of
      LDL cholesterol rose from 2.67 to 3.88 mmol/l (P < 0.01), apoB rose from 0.79 to
      1.03 g/l (P < 0.01), and the median Lp(a) concentration increased from 9.74 to
      18.97 mg/dl (P < 0.01) on treatment. Lp(a) concentrations were inversely
      associated to the size of the apo(a) molecule both before (P < 0.01) and after
      treatment (P < 0.01). The increase in Lp(a) was significant in patients with high
      molecular weight apo(a) phenotypes (n = 9; P < 0.01) and in patients with low
      molecular weight apo(a) phenotypes (n = 16; P < 0.01), but not in those with
      apo(a) "null types" (n = 6; P = 0.5). The low levels LDL cholesterol and apoB in
      untreated hyperthyroidism may result from increased LDL receptor activity. The
      increase in Lp(a) levels were not correlated with the increase in LDL cholesterol
      or apoB.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7633942
TI  - Increased induction of apoptosis in mononuclear cells of a glucose-6-phosphate
      dehydrogenase deficient patient.
AB  - Glucose-6-phosphate dehydrogenase (G6PD) deficiency belongs to the most common
      human disorders of metabolism. In affected patients generation of free radicals
      causes life-threatening hemolytic crises, for example, after consumption of
      certain drugs and foods or after infections. Rather than erythrocytes we analyzed
      mononuclear white blood cells of a patient suffering from G6PD deficiency with
      respect to their ability to enter apoptosis after treatment with daunorubicin,
      ionizing radiation, or dexamethasone. The induction of apoptosis was increased in
      G6PD-deficient cells compared to cells from eight normal donors. In parallel, the
      glutathione content of mononuclear cells from the G6PD-deficient patient was
      significantly decreased. While in affected patients decreased life span of
      erythrocytes damaged by oxidative stress has long been recognized as the
      mechanism underlying hemolysis, peripheral leukocytes have not received similar
      attention. Induction of apoptosis is a relatively complex process that has been
      linked to cellular glutathione content. This is the first report investigating
      G6PD deficiency and apoptosis.

PMID- 7633943
TI  - Gesellschaft Deutscher Naturforscher und Arzte: the tradition of integrating
      basic science with medicine.

PMID- 7633945
TI  - Gene transfer by viral vectors for gene therapy.

PMID- 7633946
TI  - Retroviral transfer of HSV1-TK gene into human lung cancer cell line.
AB  - We used a recombinant retrovirus as one of the potential vectors for human gene
      therapy to transfer a drug sensitivity gene into human lung cancer cells. The
      gene encoding the thymidine kinase (TK) of herpes simplex virus type 1 (HSV1) was
      used as the drug sensitivity gene. The antiherpes drugs acyclovir (ACV) and
      ganciclovir (GCV) were chosen to test the HSV1-TK activity transferred into the
      human lung cancer cell lines. The rationale for this approach was that ACV and
      GCV are nucleoside analogs specifically converted by HSV1-TK to a toxic form
      capable of inhibiting DNA synthesis or disrupting cellular DNA replication. The
      results obtained from our experiments demonstrate that the retroviral vector
      mediated HSV1-TK gene transfer leads to ACV- and GCV-dependent cytotoxicity in
      human lung cancer cell lines, including both small-cell carcinoma and non-small
      cell carcinoma. Although the gene transfer of HSV1-TK gene into tumor cells would
      be one model for gene therapy to control lung cancer, further investigations are
      necessary for the proper choice of the therapeutic gene and vector targeting such
      as tumor cell specific delivery of the gene or tumor cell specific expression of
      the transduced gene.

PMID- 7633944
TI  - The role of vitamin E in normal and damaged skin.
AB  - The generation of free oxygen radicals is believed to play an important
      pathogenic role in the development of various disorders. More than other tissues,
      the skin is exposed to numerous environmental chemical and physical agents such
      as ultraviolet light causing oxidative stress. In the skin this results in
      several short- and long-term adverse effects such as erythema, edema, skin
      thickening, wrinkling, and an increased incidence of skin cancer or precursor
      lesions. However, accelerated cutaneous aging under the influence of ultraviolet
      light, usually termed photoaging, is only one of the harmful effects of continual
      oxygen radical production in the skin. Others include cutaneous inflammation,
      autoimmunological processes, keratinization disturbances, and vasculitis. Vitamin
      E is the major naturally occurring lipid-soluble non-enzymatic antioxidant
      protecting skin from the adverse effects of oxidative stress including
      photoaging. Its chemistry and its physiological function as a major antioxidative
      and anti-inflammatory agent, in particular with respect to its photoprotective,
      antiphotoaging properties, are described by summarizing animal studies, in vivo
      tests on human skin and biochemical in vitro investigations. The possible
      therapeutic use in different cutaneous disorders, and pharmacological and
      toxicological aspects are discussed. Many studies document that vitamin E
      occupies a central position as a highly efficient antioxidant, thereby providing
      possibilities to decrease the frequency and severity of pathological events in
      the skin. For this purpose increased efforts in developing appropriate systemic
      and local pharmacological preparations of vitamin E are required.

PMID- 7633948
TI  - Nobel Prize 1994 for medicine/physiology.

PMID- 7633947
TI  - Amplified and tissue-directed expression of retroviral vectors using ping-pong
      techniques.
AB  - Ping-pong amplification is an efficient process by which helper-free retrovirions
      replicate in cocultures of cell lines that package retroviruses into distinct
      host-range envelopes [11]. Transfection of a retroviral vector DNA into these
      cocultures results in massive virus production, with potentially endless cross
      infection between different types of packaging cells. Because the helper-free
      virus spreads efficiently throughout the coculture, it is unnecessary to use
      dominant selectable marker genes, and the retroviral vectors can be simplified
      and optimized for expressing a single gene of interest. The most efficient ping
      pong vector, pSFF, derived from the Friend erythroleukemia virus, has been used
      for high-level expression of several genes that could not be expressed with
      commonly employed two-gene retroviral vectors. Contrary to previous claims,
      problems of vector recombination are not inherent to ping-pong methods. Indeed,
      the pSFF vector has not formed replication-competent recombinants as shown by
      stringent assays. Here we review these methods, characterize the ping-pong
      process using the human erythropoietin gene as a model, and describe a new vector
      (pSFY) designed for enhanced expression in T lymphocytes. Factors that limit
      tissue-specific expression are reviewed.

PMID- 7633950
TI  - Novel experimental approaches in the study of the immunopathology in inflammatory
      bowel disease.

PMID- 7633952
TI  - Fluconazole is removed by continuous venovenous hemofiltration in a liver
      transplant patient.
AB  - Fluconazole is effective for the treatment of fungal infections. A continuous
      venovenous hemofiltration (CVVH) was necessary in a liver transplant patient with
      anuria. Fluconazole treatment was started after the diagnosis of systemic
      candidiasis. There was no adverse effect on liver function, and the
      immunosuppression with cyclosporine was not affected. It is shown for the first
      time that CVVH effectively removes fluconazole from the blood circulation by a
      clearance into the hemofiltrate of approximately 21 ml/min. These data suggest
      that the treatment of fungal infections with fluconazole does not necessitate a
      reduction of the dosage during CVVH.

PMID- 7633953
TI  - Profound vagal reactions to brain natriuretic peptide.

PMID- 7633949
TI  - Receptors and G proteins as primary components of transmembrane signal
      transduction. Part 2. G proteins: structure and function.
AB  - Seven-transmembrane receptors signal through nucleotide-binding proteins (G
      proteins) into the cell. G proteins are membrane-associated proteins composed of
      three subunits termed alpha, beta and gamma, of which the G alpha subunit
      classifies the heterotrimer. So far, 23 different mammalian G alpha subunits are
      known, which are grouped in four subfamilies (Gs, Gi, Gq, G12) on the basis of
      their amino acid similarity. They carry an endogenous GTPase activity allowing
      reversible functional coupling between ligand-bound receptors and effectors such
      as enzymes and ion channels. In addition, five G beta and seven G gamma subunits
      have been identified which form tightly associated beta gamma heterodimers. Upon
      activation by a ligand-bound receptor the G protein dissociates into G alpha and
      G beta gamma, which both transmit signal by interacting with effectors. On the G
      protein level, specificity and selectivity of the incoming signal is accomplished
      by G protein trimers composed of distinct subunits. On the other hand, many
      receptors have been shown to activate different G proteins, thereby regulating
      diverse signal transduction pathways.

PMID- 7633951
TI  - Human leukocyte interferon-alpha in cream for the management of genital herpes in
      Asian women: a placebo-controlled, double-blind study.
AB  - This double-blind, placebo-controlled study examined the clinical efficacy and
      tolerance of human leukocyte interferon-alpha (2 x 10(6) IU/g) in hydrophilic
      cream to cure patients afflicted with first episodes of genital herpes. Sixty
      patients aged 18-40 years (mean 24.5) with culture-confirmed herpes simplex
      genitalis, bearing 755 lesions (mean 12.6) were randomized to active and placebo
      groups. Patients joined the study within 7 days (mean 4.1) of the manifestation
      of lesions. Each patient was given a precoded 40-g tube containing placebo/active
      preparation with instructions on self-application of the trial medication to
      their lesions three times daily for 5 consecutive days (max. 15 topical
      applications per week). Patients were examined three times a week to evaluate
      clinical efficacy and other beneficial effects. A reepithelialized lesion with
      some residual erythema was recorded as healed. Patients resolved during the
      active treatment period (1-4 weeks) were spared further therapy and were
      requested to visit us as scheduled for posttreatment control after 16 weeks. From
      the remaining patients empty tubes were collected, and similarly coded
      replacement tubes were given to continue the treatment (in total 160 tubes were
      used). Patients treated with leukocyte interferon-alpha cream had significantly
      shorter mean duration of viral shedding/healing than placebo recipients, (6.2
      days vs. 15 days; P < 0.01); thus the number of healed patients was 25/30 (83.3%)
      vs. 5/30 (17%; P < 0.001. Of the 60 patients 49 (81.6%) complained no drug
      related side effects.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7633956
TI  - Conventional versus endovascular surgical procedures: a no choice option.
AB  - The on-going debates on the competitiveness of endovascular and conventional
      surgery in the treatment of peripheral occlusive vascular diseases are justified
      by the fact that endovascular procedures are associated with a lower mortality
      and morbidity, require a shorter hospital stay, and are less costly than
      conventional surgery. However, scientific and economic comparisons between the
      two techniques are difficult because they cannot strictly be applied to the same
      patients. Patients who may benefit from endovascular surgery are generally at an
      earlier stage of the disease, they have claudication and short stenoses or
      occlusion. On the other hand, patients who present with severe claudication or
      critical ischaemia, in most cases, have long occlusions, multiple segmental
      disease and often require conventional surgery.

PMID- 7633955
TI  - The thirteenth meeting of the European Association for Cancer Research, Berlin,
      Germany, 25-28 September 1994.

PMID- 7633954
TI  - Industrialists set up first school of molecular medicine.

PMID- 7633957
TI  - Immunomodulation of cultured vascular endothelial cells by serial cell passage.
AB  - Endothelial cell seeding has been successful in reducing the thrombogenecity of
      prosthetic vascular grafts in animal models, but results from clinical trials
      have been largely disappointing. These poor results have been associated with
      poor graft coverage in immediate seeding trials, and failure of cell culture in
      staged procedures. These problems could be largely overcome by utilising a bank
      of allogeneic endothelial cells, providing an ever ready supply. However, one
      potential pitfall with this technique would be the possibility of a rejection
      response following transplantation. AIM: To study the effects of prolonged tissue
      culture, on the ability of endothelial cells to generate an immune response.
      METHODS AND RESULTS: The immunogenecity of human umbilical vein endothelial cells
      was measured using the mixed lymphocyte endothelial reaction. It was demonstrated
      that prolonged tissue culture significantly reduced the immunogenecity of the
      cells, from a mean of 7261 cpm (S.E. +/- 243, n = 3) for cells of subculture 3,
      to 5478 cpm (+/- 156, p = 0.04) for cells of subculture 7 (p = 0.04, Wilcoxon
      paired rank test), but did not significantly impair morphology or antithrombotic
      function. CONCLUSION: This study provides evidence that prolonged tissue culture
      provides morphologically and functionally intact, immunomodified endothelial
      cells which may potentially be used in seeding prosthetic vascular grafts.

PMID- 7633958
TI  - Critical limb ischaemia: management and outcome. Report of a national survey. The
      Vascular Surgical Society of Great Britain and Ireland.
AB  - AIM: A prospective national survey of patients with critical lower limb ischaemia
      was carried out to estimate the prevalence of critical lower limb ischaemia in
      Britain and Ireland; and to assess the average national outcome following
      treatment. METHOD: The surgeons were selected randomly but stratified according
      to the number of vascular surgical operations performed annually to match the
      profile of the vascular surgical population of the country as a whole. OUTCOME
      MEASURES: The main outcome measures were the primary treatment intention; final
      treatment undertaken; duration of hospital stay; final outcome in terms of
      mortality and limb salvage rates and destination on discharge. RESULTS: The data
      reveal that the extrapolated incidence of critical lower limb ischaemia in Great
      Britain and Ireland was 21,450 limbs in 20,000 patients, equating to a prevalence
      of 1 in 2500 of the population annually. Thirty per cent of the patients were
      diabetic. The overall mortality and amputation rates were 13.5% and 21.5%
      respectively. The mean duration of hospital stay was 25 days. Nearly 70% of
      patients were offered some form of revascularisation as the primary treatment
      option with a 75% chance of successful limb salvage. Amputation was associated
      with a significantly higher mortality (Chi square = 10.79, p = 0.001), longer
      hospital stay (t = 4.589, p < 0.0001) and a greater proportion of patients
      requiring long-term institutional support, than revascularisation. The ratio of
      revascularisation to amputation was 4:1. Surgeons with a lower annual experience
      of patients with vascular disease tended to undertake fewer revascularisations
      (Chi square = 6.737, p = 0.0094) and more amputations (Chi square = 10.445, p =
      0.0012) than those treating larger numbers. The mean limb salvage rate achieved
      by surgeons with a lower throughput of vascular operations was significantly
      lower that achieved by other groups of surgeons (Chi square = 7.544, p = 0.0045).

PMID- 7633959
TI  - Intraluminal aortic graft/stent combination for the treatment of life-threatening
      congenital arteriovenous malformation.

PMID- 7633961
TI  - Peripheral arterial embolism due to a renal sarcoma.

PMID- 7633960
TI  - Non-aneurysmal suppurative aortic rupture.

PMID- 7633962
TI  - Recanalisation of the native artery following failure of a bypass graft.

PMID- 7633963
TI  - Extrinsic compression of the external iliac vein following total hip
      arthroplasty.

PMID- 7633965
TI  - Carotid artery plaque composition--relationship to clinical presentation and
      ultrasound B-mode imaging. European Carotid Plaque Study Group.
AB  - OBJECTIVE: To correlate B-mode ultrasound findings to carotid plaque histology.
      DESIGN: European multicentre study (nine centres). MATERIAL AND METHODS: Clinical
      presentation and risk factors were recorded and preoperative ultrasound Duplex
      scanning with special emphasis on B-mode imaging studies was performed in 270
      patients undergoing carotid endarterectomy. Perioperatively, macroscopic plaque
      features were evaluated and the removed specimens were analysed histologically
      for fibrous tissue, calcification and 'soft tissue' (primarily haemorrhage and
      lipid). RESULTS: Males had more soft tissue than females (p = 0.0006),
      hypertensive patients less soft tissue than normotensive (p = 0.01) and patients
      with recent symptoms more soft tissue than patients with earlier symptoms (p =
      0.004). There was no correlation between surface description on ultrasound images
      compared to the surface judged intraoperatively by the surgeon. Echogenicity on B
      mode images was inversely related to soft tissue (p = 0.005) and calcification
      was directly related to echogenicity (p < 0.0001). Heterogeneous plaques
      contained more calcification than homogeneous (p = 0.003), however, there was no
      difference in content of soft tissue. CONCLUSION: Ultrasound B-mode
      characteristics are related to the histological composition of carotid artery
      plaques and to patient's history. These results may imply that patients with
      distant symptoms may be regarded and treated as asymptomatic patients whereas
      asymptomatic patients with echolucent plaques should be considered for carotid
      endarterectomy.

PMID- 7633964
TI  - Carotid endarterectomy contralateral to an occluded carotid artery: a
      retrospective case-control study.
AB  - OBJECTIVES: To analyse whether contralateral occlusion represents an additional
      perioperative risk factor in carotid endarterectomy (CEA), and whether long-term
      survival after surgery in patients with contralateral occlusion differs from that
      of patients without. DESIGN: Retrospective clinical study. SETTING: Vascular
      Surgery Unit, Department of Surgery, University of Perugia, Perugia, Italy.
      MATERIALS: Fifty-five patients with carotid stenosis and contralateral occlusion
      undergoing CEA (Group 1) were compared with 110 patients (Group II), without
      contralateral occlusion selected from a cohort of 367 patients with a patent
      contralateral artery, matched for gender, age and ipsilateral symptoms. CHIEF
      OUTCOME MEASURES: Perioperative stroke/death rate at 30 days and minor
      complications in Group I vs. Group II over a mean follow-up of 38 months. MAIN
      RESULTS: The perioperative stroke/death rate at 30 days was 0% in Group I and
      2.7% in Group II (p = 0.6) while minor complications amounted to 11% in Group I
      and 5% in Group II (p = 0.2). Survival rates of patients free from stroke, using
      Kaplan Meier curves, were 79.4% in Group I and 83.3% in Group II (p = 0.4);
      stroke free rates were 92.8% and 94.3% in Groups I and II, respectively. The
      incidence of late stroke, fatal or not, in patients who had undergone CEA with
      contralateral obstruction was the same as in similarly operated patients without
      contralateral obstruction (7% vs. 6%). However, the incidence of late vascular
      death, exemplified by a crude rate of 14% vs. 6% (p = 0.1; O.R. = 2.50; C.I. =
      0.77-8.25) was greater in patients with contralateral occlusion. CONCLUSIONS: In
      this study, CEA in patients with contralateral occlusion was not associated with
      an increased perioperative morbidity/mortality rate. The higher incidence of
      vascular death in the late follow-up of patients with contralateral carotid
      occlusion, although not statistically significant, could indicate the presence of
      more severe systemic vascular disease.

PMID- 7633966
TI  - Thromboxane and neutrophil changes following intermittent claudication suggest
      ischaemia-reperfusion injury.
AB  - OBJECTIVES: It has been postulated that ischaemia-reperfusion occurs in
      intermittent claudication resulting in neutrophil activation and release of
      soluble mediators, increasing systemic vascular permeability and enhancing
      atherogenesis. METHODS: We measured neutrophil deformability, plasma thromboxane
      levels, and urinary microalbumin excretion in 30 male claudicants, and 10 age-
      and sex-matched controls, before and after exercise to maximum walking distance.
      Blood was taken from an antecubital vein. RESULTS: There was an increase in
      urinary microalbumin excretion after exercise in claudicants. Statistically
      significant increases in the median and 90th percentile transit times (markers of
      neutrophil deformability) for isolated neutrophils from blood drawn 5 min after
      exercise in the claudicants were observed with no change in control subjects.
      Plasma thromboxane concentrations in claudicants increased within 10 min post
      exercise. Plasma concentrations in controls were significantly lower throughout
      the study period. In the claudicant group, a positive correlation between the
      percentage change in the median transit time for neutrophils, and the percentage
      change in plasma thromboxane at 60 min post-exercise was found. CONCLUSIONS: The
      results lend further support to the concept of ischaemia-reperfusion events in
      patients with intermittent claudication, leading to a systemic increase in
      vascular permeability as a result of endothelial injury or dysfunction (a crucial
      step in atherogenesis), associated with thromboxane production and neutrophil
      activation. We suggest that the above changes may contribute to the increased
      mortality seen in such patients.

PMID- 7633967
TI  - Alterations in intracranial volume following cross-clamping of the descending
      thoracic aorta in pigs--an experimental study using MRI.
AB  - OBJECTIVES: To determine whether alterations in intracranial volume occurred
      following cross-clamping of the descending thoracic aorta in pigs. DESIGN AND
      SETTING: Laboratory animal study. MATERIALS: Eight pigs undergoing cross-clamping
      of the descending thoracic aorta for 30 min. CHIEF OUTCOME MEASURES: A Philips
      Gyroscan T5-II Release 3 (0.5 T) was used to obtain intracranial images before
      cross-clamping, during cross-clamping and after declamping. The ventricular
      volume was measured on Spin Echo T1-weighted images. The signal intensity of the
      cerebral tissue was measured on Spin Echo T2-weighted images. Increased signal
      intensity of the cerebral tissue relative to an external reference was used as an
      indicator of cerebral oedema. MAIN RESULTS: The ventricular volume decreased to
      89% (p < 0.01) of the baseline value after 5 min of cross-clamping. At 5 min
      after declamping the ventricular volume decreased further to 71% (p < 0.01). At
      25 min after declamping the ventricular volume had returned to the baseline
      value. The signal intensity of the cerebral tissue did not differ from baseline
      values following aortic cross-clamping. CONCLUSIONS: In this study, ventricular
      volume decreased following cross-clamping of the descending thoracic aorta. Since
      no cerebral oedema was observed, the decrease of ventricular volume was most
      likely due to increased intracranial blood volume.

PMID- 7633968
TI  - Risk factors leading to arterial occlusion following diagnostic arteriography.
AB  - OBJECTIVES: Arteriography may precipitate occlusive complications in stenotic
      vessels by a toxic effect on the vascular endothelium, leading to intra-arterial
      thrombosis. The aim of this retrospective study was to determine the incidence of
      arterial occlusion following arteriography. METHODS: We studied 101 consecutive
      patients (71 male, 30 female; median age 72 years) undergoing percutaneous
      transluminal angioplasty (PTA) of stenotic lesions, which had been identified on
      diagnostic arteriograms performed a median of 109 days (range 6-519) previously.
      One hundred and thirty-one arterial stenoses suitable for PTA were identified in
      the patient cohort. RESULTS: Seventeen patients (17%) progressed to occlusion in
      the period between diagnostic arteriography and PTA. Stenoses in the femoro
      popliteal segment (21%) progressed to occlusion more frequently than lesions of
      the iliac arteries (3%). Independent risk factors were analysed to determine the
      risk factors predisposing to arterial occlusion following diagnostic
      arteriography. Both groups were well matched for age and sex. The mode of
      presentation, the presence of ischaemic heart disease, hypertension, diabetes or
      current smoking habits did not predict progression of disease to arterial
      occlusion. However, the rate of occlusion appeared to be influenced by the
      proportion of patients taking anti-platelet medication (51% in non-occluders as
      compared to 11% in patients who occluded, 95% CI 0.1 to 10), and to the length of
      time between arteriography and PTA (median of 92 days in non-occluders as
      compared to 125 days in patients who occluded, 95% CI 21 to 57). CONCLUSIONS:
      These data demonstrate that occlusion of pre-existing arterial stenoses following
      diagnostic arteriography is significantly more frequent in patients not taking
      anti-platelet medication and when the time interval between arteriography and PTA
      exceeds 92 days. To minimise thrombotic arterial occlusion both diagnostic and
      therapeutic procedures should be performed simultaneously, but if a delay is
      unavoidable, patients should be treated with anti-platelet medication, which
      reduces the incidence of arterial occlusion.

PMID- 7633969
TI  - The cost-effectiveness of treatment of short occlusive lesions in the
      femoropopliteal artery: balloon angioplasty versus endarterectomy.
AB  - OBJECTIVE: To compare the short- and long-term outcome and the costs involved in
      balloon angioplasty (BA) and thromboendarterectomy (EA) of short femoropopliteal
      occlusions. DESIGN: Retrospective study. PATIENTS AND METHODS: Forty-one lower
      limbs underwent EA from 1980 until 1988 and BA was performed in 62 limbs between
      1988 and 1993. The two groups of patients were well matched for age, gender,
      cardiovascular risk-factors and the length of the femoropopliteal occlusions. In
      addition to clinical follow-up colour-Duplex scanning and intraarterial DSA were
      performed. Complete occlusions or significant restenoses were considered failure
      of the reconstruction. Actual costs were calculated by the hospital economic
      administration. RESULTS: The 3-year primary patency in EA patients was 87% and in
      the BA group 44% (p = 0.0002). Redo procedures were required in seven (17%)
      patients with EA and in 24 (39%) with BA. Patency after redo procedures, i.e.
      tertiary patency, was 94% and 74% after 3 years in the EA and BA group
      respectively (p = 0.14). The mean cost of the primary treatment was higher in EA
      than in BA patients (p < 0.0001). Mean total treatment costs including the
      expenses involved with redo procedures were also higher in the group with EA than
      with BA (p < 0.001). However, the cost-effectiveness expressed as the total costs
      per month tertiary patency, was not significantly different for the two treatment
      groups; in patients with EA the ratio of total treatment costs and tertiary
      patency was NFl 309, and in patients with BA NFl 287. CONCLUSION: Contrary to the
      general view the expenses associated with surgical treatment are comparable with
      those of an endovascular procedure, if the costs are expressed as a cost-to
      patency ratio.

PMID- 7633970
TI  - Surgical management of complications following endoluminal grafting of abdominal
      aortic aneurysms.
AB  - OBJECTIVE: The aim of this study was to report the outcome of endoluminal
      grafting of abdominal aortic aneurysms (AAA) with special reference to
      complications. METHODS: Between May 1992 and August 1994 endoluminal repair of
      aneurysms was undertaken in 61 patients. In 53 the aneurysm was aortic and these
      are the basis of this report. In patients with AAA all procedures were elective
      and were performed in the operating room with the patient draped for an open
      repair in the event of failed endoluminal repair. The configuration of the
      endografts was tubular 36, tapered aortoiliac/aortofemoral 12 and bifurcated 5.
      Radiographic guidance was used to pass the endografts into the aorta via a
      delivery sheath introduced through the femoral or iliac arteries. RESULTS:
      Successful endoluminal repair of AAA was achieved in 43 of 53(81%) patients. In
      the remaining 10 patients, endoluminal repair was abandoned in favour of an open
      repair. There were 17(32%) local/vascular and 13(25%) systemic/remote remote
      complications. The sum of these complications occurring in successful endoluminal
      repairs and those complications leading to failure of endoluminal repair was
      40(75%). There were two cardiac deaths within 30 days in patients undergoing
      endoluminal repair (both procedure related) and four late deaths (unrelated to
      aneurysm repair). Three of the late deaths were in patients undergoing
      endoluminal repair and one endoluminal converted to open repair. CONCLUSION:
      Endoluminal repair of AAA in our experience has a low perioperative (< 30 days)
      mortality rate (3.7%) but a high morbidity rate (75%). It is recommended that
      complications be classified into three groups: systemic/remote and local/vascular
      (following successful endoluminal repair) plus those complications leading to
      failure of endoluminal repair. The first group is composed of medical
      complications while the latter two groups comprise those surgical complications
      directly related to the endoluminal technique.

PMID- 7633971
TI  - Topographical evaluation of skin perfusion patterns in peripheral arterial
      occlusive disease by means of computer-assisted fluorescein perfusography.
AB  - OBJECTIVE: To evaluate the clinical impact of computer-assisted fluorescein
      perfusography in peripheral arterial occlusive disease (PAOD). DESIGN: Foot and
      calf skin perfusion was visualised by intravenous fluorescein injection.
      Fluorescein influx was recorded photographically and converted into functional
      images of fluorescein appearance times (AT) by means of digital film processing.
      SETTING: Vascular Laboratory of Clinic for Vascular Disease. MATERIALS: 249
      patients with PAOD. Among 481 limbs studied, 83 legs presented with patent
      arteries, 70 with asymptomatic obstructions (Stage I), 170 with claudication
      (Stage II) and 158 with rest pain and skin lesions (Stage III/IV). CHIEF OUTCOME
      MEASURES: Forefoot and calf mean ATs and standard deviations (SD) served as
      arbitrary measures of regional skin perfusion rates and their homogeneity,
      respectively. MAIN RESULTS: In the control legs, a homogeneous and fast
      fluorescence appearance was observed (medians at the foot: AT33.4 s, SD 3.6). In
      stage II disease, AT (39.9 s, SD 5.6) were slightly impaired as compared to limbs
      with patent arteries or stage I disease (p < 0.01). Ninety-seven out of the 158
      legs in stage III/IV could be managed by conservative therapy. According to
      fluorescein-perfusography, they did not differ from stage II disease (AT 38.8 s,
      SD 6.1). Sixty-one limbs were clinically affected by critical ischaemia. They
      exhibited a markedly delayed and heterogenous fluorescein influx at the foot (AT
      77.3 s, SD 26.5, p < 0.01 vs all other groups). Non-fluorescent areas occurred in
      53% compared to only 1% of limbs with and without critical ischaemia,
      respectively. Retrospectively, predictive values of fluorescein perfusography in
      identifying a critical limb ischaemia (accuracy 93%) were superior to the ankle
      systolic arterial pressure determination (accuracy 80%). CONCLUSIONS: Fluorescein
      perfusography seems to be of diagnostic and prognostic use in PAOD in stage
      III/IV where inflammatory and ischaemic patterns of dye appearance can be
      distinguished.

PMID- 7633972
TI  - Reduction of requirement for leg vascular surgery during long-term treatment of
      claudicant patients with ticlopidine: results from the Swedish Ticlopidine
      Multicentre Study (STIMS).
AB  - OBJECTIVE: To study the effect of long-term treatment of the platelet inhibitor
      ticlopidine as secondary prevention against the need of vascular surgery in
      patients with intermittent claudication. DESIGN: The Swedish Ticlopidine
      Multicentre Study (STIMS), was conducted in six medical and surgical clinics of
      university hospitals in Sweden. METHODS: 687 claudicants were randomised to
      ticlopidine 250 mg bd or placebo and vascular surgery events were recorded
      prospectively over a 7-year period. Cox proportional hazards models of risk for
      leg vascular surgery were constructed using drug treatment and 11 putative risk
      factors for vascular disease as covariates. Surgical event-free survivals were
      compared by Kaplan-Meier analysis. RESULTS: The overall rate of first operations
      was 2.4% per annum. More than half of these operations were in the aortoiliac
      region. One-quarter of patients operated during the period required further
      operations but amputation was rare. Ticlopidine treatment reduced the need for
      vascular reconstructive surgery by about half, both in intention-to-treat and on
      treatment analyses (unadjusted relative risks 0.486, 95% CI 0.317-0.745; p <
      0.001; 0.493, 95% CI 0.290-0.841: p < 0.01, respectively). In Cox model analysis
      only male sex was confirmed as a risk factor for surgery. Previous peripheral
      arterial surgery was the strongest predictor of the need for surgery. None of the
      risk factors examined interacted statistically with the effect of treatment with
      ticlopidine. CONCLUSION: In patients with intermittent claudication it seems
      possible to prevent the need for future vascular surgery by the use of platelet
      inhibition with ticlopidine.

PMID- 7633973
TI  - Carotid artery duplex scanning: does plaque echogenicity correlate with patient
      symptoms?
AB  - In this study we have investigated the relationship between plaque sonolucency
      and ipsilateral hemispheric symptoms in 116 patients at risk of cerebrovascular
      disease (75 symptomatic patients, 41 asymptomatic patients). Our results indicate
      that plaque sonolucency is significantly associated with the incidence of patient
      symptoms at presentation. Twice as many symptomatic vessels contained the
      predominantly sonolucent plaque types (types 1 and 2) compared to contralateral
      asymptomatic vessels (p = 0.039, odds ratio = 2.9). Vessel stenosis also had a
      significant association with patient symptoms. No significant interaction was
      shown between vessel stenosis and plaque sonolucency (p = 0.15, odds ratio =
      1.0). A model using vessel stenosis and plaque echogenicity as independent
      variables showed that degree of vessel stenosis had a closer association with
      incidence of symptoms (p = 0.03, odds ratio = 1.04) than plaque type (p = 0.13,
      odds ratio = 0.51).

PMID- 7633975
TI  - Endovascular femoropopliteal bypass: a cadaveric study.
AB  - OBJECTIVE: Patency rates of standard femoropopliteal bypass in infra-inguinal
      occlusive disease have yet to be matched by minimally invasive percutaneous
      procedures. We report a feasibility study of a less invasive endovascular
      femoropopliteal bypass technique. METHODS: (1) groin exposure of femoral artery,
      (2) guidewire passage and mechanical dilatation of superficial femoral artery
      (SFA), (3) expandable helical cutter endarterectomy of SFA, (4) transluminal
      placement of PTFE graft, (5) graft balloon dilatation to shape and set distal
      interface and (6) end-to-end anastomosis of proximal graft to femoral artery.
      Development and testing was undertaken in 48 limbs of 26 fresh human cadavers.
      Limbs with no demonstrable SFA disease were excluded. Seventeen limbs had mild,
      diffuse disease. Three limbs had a single, short, tight stenosis. Seventeen limbs
      had multiple, high grade stenotic lesions 12-40 cm long (mean 24 cm). Eleven
      limbs had occlusive lesions, 8-38 cm long (mean 24 cm). RESULTS: We successfully
      completed the procedure in 39 (81%) limbs. We failed to complete the procedure in
      nine limbs; four from failed guidewire passage, four from vessel avulsion, and
      one from graft deployment failure. Histology confirmed endarterectomy cleavage in
      the standard plane. Angiography and explants demonstrated a patent graft and
      popliteal artery, and smooth distal graft/arterial interface with no obvious
      defects in 24 (62%) cases. Defects included combinations of: contrast
      extravasation/reflux, graft malpositioned/incorrectly sized, distal graft fold,
      and distal intimal flap. CONCLUSION: Endovascular femoropopliteal bypass is
      feasible and warrants further studies for possible clinical application.

PMID- 7633974
TI  - A randomised, clinical study of the effect of low-dose dopamine on central and
      renal haemodynamics in infrarenal aortic surgery.
AB  - OBJECTIVE: To determine whether dopamine prevents deterioration of central
      haemodynamics and renal function in aortoiliac surgery. DESIGN: Prospective,
      randomised and placebo-controlled. SETTING: University hospital. MATERIALS:
      Thirty patients for elective vascular surgery with implantation of an
      aortobifemoral or an aortobiiliac graft due to aortoiliac arteriosclerosis had
      infusion of dopamine 3 micrograms/kg/min or placebo during the operation and 24 h
      postoperatively. Thoracic epidural analgesia and general anaesthesia were used.
      CHIEF OUTCOME MEASURES: Central haemodynamic measurements were registered. The
      effective renal plasma flow (ERPF), the glomerular filtration rate (GFR),
      angiotensin II, aldosterone, arginine vasopressin (AVP), atrial natriuretic
      peptide (ANP), endothelin and excretion of water and electrolytes were measured
      preoperatively, 1 h postoperatively and 24 h postoperatively. MAIN RESULTS:
      During the operation the dopamine group had higher cardiac index and heart rate
      together with lower pulmonary artery wedge blood pressure. ERPF and GFR did not
      differ between the groups. In the dopamine group ERPF was increased in all
      patients at the first postoperative clearance. The fractional excretion of
      sodium, the per- and postoperative diuresis and AVP were increased in the
      dopamine group as compared to the placebo group. Postoperatively, ANP in the
      placebo group was raised as compared to the preoperative level. CONCLUSIONS:
      Peroperatively, dopamine counteracted depression of left ventricular function.
      The increased ERPF at the first postoperative clearance in the dopamine group
      indicates either improved peroperative haemodynamics or a synergistic effect
      between dopamine and epidural sympathetic blockade. Dopamine also improved
      diuresis and natriuresis.

PMID- 7633976
TI  - Fibrin sealant reduces suture line bleeding during carotid endarterectomy: a
      randomised trial.
AB  - OBJECTIVES: To determine whether topical fibrin sealant reduced suture line
      bleeding during carotid endarterectomy with polytetrafluoroethylene (PTFE) patch
      closure. DESIGN: Prospective randomised non-blinded control trial. SETTING:
      Regional vascular surgery unit. MATERIALS: Seventeen patients undergoing carotid
      endarterectomy were randomised either to receive fibrin sealant as a topical
      haemostatic agent at the arteriotomy suture line or to act as control. OUTCOME
      MEASURES: Time taken to achieve haemostasis at the suture line. Intraoperative
      blood loss. Total operative time. RESULTS: The median time to achieve haemostasis
      was 5.5 min (range 4-31 min) in the treatment group and 19 min (range 10-47 min)
      in the control group. This difference was statistically significant p < 0.005 by
      Mann-Whitney test. There was no statistical difference in total operative time.
      Operative blood loss was lower in the treatment group (median 420ml, range 300
      500ml) than in the control group (median 550ml, range 350-1200ml) but this
      difference was not statistically significant. One patient in the control group
      suffered a perioperative thrombo-embolic event. CONCLUSION: Fibrin sealant is an
      effective topical haemostatic agent for arteriotomy suture lines involving PTFE
      material.

PMID- 7633977
TI  - The abnormal aorta: a statistical definition and strategy for monitoring change.
AB  - OBJECTIVES: This study defines a protocol for monitoring the growth of small
      abdominal aortic aneurysms based on age-related abnormality thresholds, observed
      aortic growth patterns and the limits of precision of the measurement technique.
      DESIGN: 13000 men aged 60 - 75 years were invited to their GP's surgery for
      measurement of the maximum diameter of the infrarenal aorta. Seventy-six percent
      responded and measurement was possible in 97.1% of the respondents. The AP
      diameter of the aorta was measured according to a strict protocol, with a
      portable ultrasound scanner. SETTING: Cases were recruited from the conurbation
      of Birmingham and Solihull, U.K. CHIEF OUTCOME MEASURE: A statistical description
      of the differences in distributions of aortic diameters of four age groups of
      males. MAIN RESULT: The aorta expands in diameter during the seventh and eighth
      decade for up to 25% of all those screened. The order of magnitude of this change
      is similar to that previously attributed to the growth of small aneurysms. Age
      related thresholds for abnormality should range from 24 mm for a 60 year old to
      37 mm for a 75 year old. CONCLUSIONS: Using data on the expected maximum rate of
      change of the dilated aorta and statistically derived thresholds from this
      analysis a monitoring strategy is suggested for those with an abnormal aorta.

PMID- 7633978
TI  - The post-carotid endarterectomy hyperperfusion syndrome.

PMID- 7633979
TI  - Carotid plaque morphology: a review.
AB  - The recent North American Symptomatic Carotid Endarterectomy Trial has answered
      fairly conclusively the questions concerning the optimal management of patients
      with symptoms who have a > 70% stenosis of the internal carotid artery. It has
      also had the effect of refocusing attention on carotid pathology. The main
      question still to be answered is whether surgical management is the optimum
      treatment for other groups of patients with carotid disease. From various studies
      done on the natural history of carotid plaques it is apparent that there are
      subgroups who may benefit from surgery, namely those who will progress to stroke
      if not treated. The problem comes in identifying these subgroups by the factors
      which cause them to progress. This paper aims to review the role that plaque
      morphology has in the development of symptoms and whether it should be included
      with degree of stenosis in assessing the risk of a carotid plaque. The non
      invasive assessment of plaque morphology is also reviewed. The evidence from this
      review does not support the use of plaque morphology as a discriminating factor
      for carotid endarterectomy at present.

PMID- 7633980
TI  - Intraoperative determinants of infrainguinal bypass graft patency: a prospective
      study.
AB  - OBJECTIVES: To evaluate a number of currently available methods for
      intraoperative assessment of infrainguinal bypass grafts (IBG) in terms of
      detecting technical errors and predicting graft failure. DESIGN: Prospective open
      clinical study. METHODS: Forty-nine patients undergoing 54 consecutive IBG were
      studied. Intraoperatively, the following measurements were performed: distal
      pulse palpation (DPP), continuous wave Doppler (CWD), pulse volume recording
      (PVR), and ultrasonic volume flowmetry (UVF), followed by intraoperative
      angiography of the entire graft and runoff vessels. The outflow resistance was
      graded according to the guidelines of the Society for Vascular Surgery and
      International Society for Cardiovascular Surgery (SVS/ISCVS runoff score). Graft
      patency was determined noninvasively (PVR, colour Duplex) up to 12 months
      following surgery. Predictive values and likelihood ratios for the intraoperative
      tests in detecting a technical problem during the bypass procedure and in
      predicting early graft failure were calculated. RESULTS: There were five
      immediate revisions for problems detected intraoperatively. Angiography did not
      identify any additional problems but assisted in the correct location of the
      problems detected by the other tests. DPP and CWD were highly significant
      indicators of the need for revision with likelihood ratios for a positive test of
      14.7 (p < 0.01) and 12.3 (p < 0.01) respectively. PVR did not achieve statistical
      significance in this respect. None of the intraoperative tests was a
      statistically significant predictor of early graft failure. The SVS/ISCVS runoff
      score, on the other hand, predicted early failure with a PPV of 33% (likelihood
      ratio for a positive test of 4.9, p < 0.05). None of the grafts with a perfect
      SVS/ISCVS runoff score (n = 39) failed in the first postoperative month.
      CONCLUSIONS: Simple CWD insonation of graft and anastomoses is the best
      intraoperative indicator for technical inadequacies after IBG. Routine
      intraoperative angiography is not necessary and intraoperative anatomical imaging
      may be reserved for situations in which noninvasive documentation of technical
      success is absent. Contrary to the intraoperative haemodynamic test results, the
      SVS/ISCVS runoff score is a good predictor of early graft failure.

PMID- 7633981
TI  - Dynamic quantification, visualisation and animation of blood velocities and flows
      in infrarenal aortic aneurysms in vivo by three-dimensional MR phase velocity
      encoding.
AB  - OBJECTIVES: Nuclear magnetic resonance (MR) phase velocity encoding techniques
      were developed for assessment of three-dimensional blood flow patterns and
      regional blood flows in infrarenal aortic aneurysms in vivo. METHODS: Twenty
      patients with abdominal aortic aneurysms were investigated before elective
      surgery with a 1.5 Tesla MR-scanner. Standard multislice spin-echo sequences were
      used for aneurysm imaging. A flow-adjusted gradients sequence (FLAG) provided
      three-dimensional vector plots depicting local blood flow velocities as functions
      of time and anatomical position. Computer-generated animated presentations of the
      vectors were developed to ease data analysis and interpretation. RESULTS: The
      blood flow patterns in infrarenal aortic aneurysms were much more complex than
      previously believed. Their main characteristics were simultaneous breakdown of
      the antegrade flow and creation of major retrograde flow components. Major
      pattern determinants included inlet geometry and lumen morphology, especially
      presence or absence of a thrombus. CONCLUSIONS: The frictional forces generated
      within the lumen as a result of the breakdown of laminar flows are probably
      translated to the aneurysm wall and contribute to thrombus formation, aneurysm
      growth and risk of rupture.

PMID- 7633982
TI  - Computer-assisted carotid plaque characterisation.
AB  - OBJECTIVE: To determine the relationship between plaque echogenicity as measured
      by computer and the incidence of cerebral brain infarction. PATIENTS AND METHODS:
      Eighty-seven patients with 148 plaques producing more than 50% internal carotid
      artery stenosis were studied. Sixty-nine plaques were in asymptomatic patients,
      35 were associated with amaurosis fugax, 19 with transient ischaemic attacks and
      25 with stroke. All patients had a CT brain scan and the presence of ipsilateral
      cerebral infarction was noted. Images of the plaques obtained with an ATL
      Ultramark-4 Duplex scanner (7.5 MHz high resolution probe) were transferred to a
      computer. Using an image analysis program a histogram for each plaque was
      obtained with the number of pixels plotted against the grey scale (0-225). The
      median of the grey scale was used as a measure of echogenicity. RESULTS: Fifty
      three (36%) of the 148 plaques were associated with ipsilateral CT brain
      infarction. Plaques with a grey scale median more than 32 (echogenic) were
      associated with an incidence of 11% (7/64) CT infarction. In contrast, plaques
      with grey scale median below or equal to 32 (echolucent) were associated with 55%
      (46/84) incidence of CT infarction (chi 2 = 30.35, p < 0.001, relative risk = 22,
      95% confidence interval from 4.7 to 108). CONCLUSION: This study indicates that
      computer analysis of carotid plaque can identify high-risk carotid plaques. The
      potential of such analysis in the identification of asymptomatic high-risk
      patients should be explored in further studies.

PMID- 7633983
TI  - Femorodistal venous bypass evaluated with intravascular ultrasound.
AB  - OBJECTIVE: To evaluate the feasibility of intravascular ultrasound imaging during
      femorodistal venous bypass procedures to assess qualitative and quantitative
      parameters of the greater saphenous vein and to detect potential causes for
      (re)stenosis and/or occlusion. METHODS: Intravascular ultrasound data obtained
      from 15 patients were reviewed and compared with angiographic data. RESULTS:
      Intravascular ultrasound enabled differentiation between normal and thickened
      vein wall. Venous side-branches could be located. Intact valves could be
      differentiated from valves disrupted by valve cutting. Patent anastomoses could
      be distinguished from anastomoses with some degree of obstruction. Intravascular
      ultrasound imaging of the inflow and outflow tracts revealed obstructive lesions,
      not evidenced angiographically. Quantitative analysis revealed that the median
      normal vein wall thickness (tunica intima and tunica media) was 0.25 mm (range
      0.17-0.40 mm). The distinct vein wall thickening encountered in three patients
      measured 0.82, 0.95 and 1.06 mm, respectively, and was associated with narrowing
      in two patients. In five of 15 patients intravascular ultrasound findings altered
      surgical management. CONCLUSION: Intravascular ultrasound is able to assess
      qualitative and quantitative parameters of the venous bypass and has the
      potential to influence surgical management based on morphologic and quantitative
      data.

PMID- 7633984
TI  - In vitro evaluation of endovascular stents to assess suitability for endovascular
      graft fixation.
AB  - OBJECTIVE: To compare and ascertain the suitability for endovascular aortic graft
      fixation of the Palmaz stent, the Strecker stent, the modified Gianturco-Z stent,
      the Wallstent and a new stent made of the shape memory alloy nitinol. DESIGN,
      SETTING AND MATERIALS: In vitro studies using a simple tensiometer to assess the
      forces required to distract each stent from porcine aorta; and using a high
      pressure, pulsatile-flow pump to measure flow rates required to dislodge stents
      holding grafts within porcine aortas, with assessment using endovascular
      ultrasound. RESULTS: The Palmaz, the modified Gianturco-Z and the nitinol stents
      resisted significantly greater distraction forces than the Wallstent, but
      endovascular ultrasound examination revealed that the modified Gianturco-Z stent
      was seen to move away from the aortic wall at high flow rates precluding adequate
      fixation. The Strecker stent could not be assessed using these techniques.
      CONCLUSIONS: A nitinol stent may be suitable for aortic graft fixation, has
      characteristics similar to the Palmaz stent and has shape memory effect which may
      overcome the difficulties of introduction of wider diameter stents through narrow
      arteries.

PMID- 7633985
TI  - An infection-resistant PTFE vascular graft; spiral coiling of the graft with
      ofloxacin-bonded PTFE thread.
AB  - OBJECTIVE: To develop an infection-resistant polytetrafluoroethylene (PTFE)
      vascular graft for potential clinical use in grafting in sites of bacterial
      contamination and in replacement of the infected grafts. SETTING: Experimental
      study in rabbits. MATERIALS AND METHODS: An antibiotic ofloxacin (OFLX) was
      bonded to a sheet of PTFE by impregnation, which was cut and twisted into fine
      threads. The in-vitro antibacterial activity of OFLX-PTFE thread was determined
      by measuring the zone of growth inhibition against Escherichia coli. The thread
      was spirally coiled around a ridged outerwall PTFE to make the OFLX-PTFE graft.
      OFLX-PTFE graft or control graft was interposed in the inferior vena cava (IVC)
      of rabbits and the entire graft was covered with fibrin containing a fixed number
      of E. coli. Three or 7 days after the grafting, the grafts with perigraft tissue
      were harvested and subjected to bacteriological studies. RESULTS: In spite of
      early phase rapid elution of OFLX, a significant antibacterial activity was
      retained for more than 2 weeks. The antibacterial activity of OFLX-PTFE threads
      implanted in the subcutaneous space of rabbits decreased to 48% after 24 h and to
      approximately 1% after a week. The swab culture of all the control grafts was
      positive, while only one of 13 PTFE-OFLX grafts was positive. The number of
      viable bacteria in the perigraft tissue of OFLX-PTFE grafts was remarkably low in
      comparison with that of control grafts. Thus, the OFLX-PTFE grafts exhibited a
      marked in-vivo antibacterial activity. CONCLUSION: By a unique method, it was
      possible to furnish PTFE graft with an excellent infection-resistant property,
      without affecting the original biological behaviour.

PMID- 7633986
TI  - The influence of fibrinogen concentration on the development of vein graft
      stenoses.
AB  - OBJECTIVE: The aim of this study was to identify factors associated with the
      development of graft stenoses in the first year after bypass. DESIGN AND SETTING:
      Between January 1992 and April 1993, 75 consecutive patients undergoing distal
      vein bypass surgery were entered into a graft surveillance programme at Charing
      Cross Hospital. The grafts (n = 79) were surveyed by colour flow Doppler
      ultrasonography at 7 days, 3, 6, 9 and 12 months and the site of stenoses (> 50%)
      recorded. Position of the distal anastomosis, graft type (in situ or reverse) and
      clinical history were recorded. At the 3-month surveillance a blood sample was
      taken for the estimation of smoking markers, lipids and fibrinogen. RESULTS: The
      site of the distal anastomosis was to the suprageniculate popliteal in nine,
      infrageniculate popliteal in 32 and tibio/peroneal vessels in 38 cases. In the
      first month following bypass there were six deaths, giving a 30 day mortality of
      7.5%, three patients were lost to follow up, seven grafts occluded, three were
      replaced by PTFE, four patients underwent amputation and one patient had a redo
      vein graft. In the remaining grafts 20/63 (32%) developed stenoses within the
      first year after bypass. The development of a graft stenosis was not associated
      with sex, diabetic status, site of distal anastomosis, graft type or serum
      lipids. Multiple regression analysis identified only one factor associated
      significantly with the development of vein graft stenosis: fibrinogen
      concentration (p = 0.003). Life table analysis showed that after 1 year only 46%
      of grafts remained free of stenoses in patients with above median fibrinogen
      concentrations compared with 84% of grafts in patients with below median
      fibrinogen concentrations, p = 0.009. CONCLUSIONS: Increased plasma fibrinogen
      concentration is a potent risk factor for the development of vein graft stenosis.
      These results prompt consideration of the role of fibrinogen in stimulating
      smooth muscle cell proliferation in the stenotic lesion.

PMID- 7633987
TI  - Effects of spinal cord stimulation (SCS) in patients with inoperable severe lower
      limb ischaemia: a prospective randomised controlled study.
AB  - OBJECTIVES: This study was designed to test the hypothesis that spinal cord
      stimulation (SCS) improves limb salvage in patients with inoperable severe leg
      ischaemia. DESIGN: Prospective randomised controlled study with 18 months follow
      up. SETTING: Vascular surgical units in two university hospitals. MATERIALS:
      Atherosclerotic (n = 41) and diabetic (n = 10) patients having chronic leg
      ischaemia with rest pain and/or ischaemic ulcerations due to technically
      inoperable arterial occlusions. CHIEF OUTCOME MEASURES: Limb salvage and amount
      of tissue loss within 18 months, pain relief. MAIN RESULTS: Twenty-five patients
      were randomized to SCS and 26 to analgesic (control) treatment. Macrocirculatory
      parameters were not different in the two groups during follow-up. Long-term pain
      relief was observed only in the SCS group. At 18 months, limb salvage rates in
      the SCS and control groups were 62% and 45% (N.S.). Tissue loss was less (p =
      0.05) in the SCS group. A subgroup analysis of patients without arterial
      hypertension showed a significantly lower amputation rate in the SCS vs the
      control group. CONCLUSIONS: SCS provided long-term pain relief but limb salvage
      at 18 months was not significantly improved by SCS in this rather small study.
      The results suggest that SCS may reduce amputation levels in patients with severe
      inoperable leg ischaemia and be most effective in patients without arterial
      hypertension.

PMID- 7633988
TI  - Intravenous pentoxifylline for the treatment of chronic critical limb ischaemia.
      The European Study Group.
AB  - OBJECTIVES: To investigate the safety and efficacy of intravenous pentoxifylline
      infusion therapy, 600 mg twice daily for up to 21 days, for the management of
      patients with chronic critical limb ischaemia (CLI). DESIGN: A prospective,
      randomised, double-blind, placebo-controlled, parallel-group, multicentre trial.
      SETTING: County and university hospitals in six European countries. MATERIALS: A
      total of 314 patients suffering from CLI were enrolled: 157 patients were
      allocated to each treatment. OUTCOME MEASURES: Patients were reviewed after 7
      days of treatment and continued in the study for up to a further 14 days if their
      condition had not deteriorated. Rest pain (assessed by pain score and visual
      analogue scale), sleep disturbances and analgesic consumption were measured.
      RESULTS: Both intention-to-treat and per protocol analyses showed significantly
      positive results in favour of pentoxifylline over placebo. Severity of rest pain
      was consistently and significantly lower as shown by the results of the pre
      infusion pain scores (p = 0.007), pain visual analogue scales (p < 0.001) and
      scores describing rest pain-related sleep disturbances (p = 0.003). Treatment
      response was not influenced by the presence of diabetes mellitus or by
      eligibility for surgery. CONCLUSION: These results justify the use of intravenous
      pentoxifylline infusion therapy for the management of rest pain in patients with
      CLI.

PMID- 7633989
TI  - Colour Doppler ultrasound in diagnosing venous insufficiency. A comparison to
      descending phlebography.
AB  - OBJECTIVE: To evaluate the technique of ultrasound colour Doppler in diagnosing
      venous valvular incompetence in the lower leg. DESIGN: Prospective clinical
      study. SETTING: Department of clinical physiology. MATERIALS: 44 patients (56
      legs) referred with a clinical diagnosis of deep venous insufficiency. CHIEF
      OUTCOME MEASURES: Colour Doppler and descending phlebography. MAIN RESULTS: Using
      phlebography as a "gold standard" the accuracy of the colour Doppler technique
      varied between 93% and 55% for the different veins. For the superficial and deep
      femoral veins, the popliteal vein and the long and short saphenous veins the
      accuracy was between 90% and 70%. The lowest correlation was found for the deep
      calf veins (55-66% accuracy). CONCLUSIONS: Colour Doppler was found to be a
      suitable technique for non-invasive investigation of patients with suspected
      venous insufficiency. Since the colour Doppler technique is non-invasive it is
      well suited for follow-up studies. Descending phlebography should be reserved as
      an adjunct technique in patients scheduled for valve reconstructive surgery.

PMID- 7633990
TI  - Assessment of stenoses in the aortoiliac tract by calculation of a vascular
      resistance change ratio before and after exercise.
AB  - OBJECTIVES: Intraarterial pressure measurement is the most reliable method to
      assess haemodynamically significant stenoses in the aortoiliac tract. We have
      tried to develop a simple and quick, non-invasive method to assess stenoses of
      this type. DESIGN: Prospective semi-blinded clinical study. METHODS: It was
      postulated that a haemodynamically significant aortoiliac tract stenosis would
      result in a lesser degree of vascular resistance decrease after vasodilatation,
      compared to patients only suffering from femorodistal stenoses. We approximated
      vascular resistance by: (brachial pressure-ankle pressure)/femoral artery mean
      Doppler velocity. By dividing vascular resistance at rest by vascular resistance
      after exercise, we calculated the Resistance Change Ratio (RCR). PATIENTS AND
      RESULTS: In 34 patients (50 legs) with arterial stenoses, the pressure gradient
      over the aortoiliac segment was compared to the RCR. Legs were divided in three
      groups: group 1 consisted of 22 legs that showed a pressure gradient > 10 mmHg at
      rest; group 2 showed a pressure gradient > 10 mmHg after papaverine; group 3
      showed a pressure gradient of 10 mmHg or less. The median RCR was: 0.74 (range:
      0.23-4.04) for group 1, 0.71 (range: 0.36-1.80) for group 2 and 0.93 (range 0.36
      2.06) for group 3. There was no significant difference between the groups (p =
      0.19). CONCLUSION: The RCR could not be used to accurately detect stenoses in the
      aortoiliac.

PMID- 7633991
TI  - When is urgent revascularization unnecessary for acute lower limb ischaemia?
AB  - OBJECTIVES: To predict the risk of gangrene by the use of simple clinical
      parameters available on admission. DESIGN: Retrospective comparison using
      logistic regression and chi2 analyses of prospectively registered data from two
      patients series. METHODS: One group of patients with acute lower limb ischaemia,
      (n = 61) was managed by selective initial non-operative treatment (NO) in a
      university hospital. The other group (n = 173) contained patients managed by
      early revascularisation in a multicentre (MC) study from 10 university, county
      and district hospitals. Gangrene and death within one month were recorded.
      RESULTS: 57% of patients in the NO group were initially managed by intravenous
      heparin followed by surgery when necessary. Impaired motor function and skin
      cyanosis in the ischaemic limb predicted gangrene. Patients without this
      combination were low risk (LR) patients and constituted 62% (NO) and 67% (MC).
      Non-operatively managed LR patients did not develop gangrene, whereas 14% of
      those undergoing early revascularisation in the two series did (p < 0.05).
      CONCLUSIONS: The results suggest that patients without motor disturbance and
      cyanosis are at low risk of gangrene and may benefit from initial non-operative
      treatment, irrespective of the presumed aetiology.

PMID- 7633993
TI  - The role of thrombolysis in the management of thromboembolic disorders: a four
      year review.
AB  - OBJECTIVE: To examine the role of thrombolysis alone, or in conjunction with
      surgery and angioplasty, in the treatment of thromboembolic disorders. DESIGN: A
      retrospective review of 70 patients, who received thrombolysis on 73 occasions
      between 1990 and 1993. PATIENTS AND METHODS: Four groups were defined: (1)
      thrombolysis alone (40%); (2) thrombolysis followed by angioplasty (23%); (3)
      thrombolysis followed by surgery (13%) and (4) thrombolysis after failed
      angioplasty (24%). RESULTS: Twenty-eight patients (40%) received thrombolysis
      alone of which 13 were successful. In 25 cases (36%) thrombolysis was initially
      successful in that it permitted further angioplasty or surgical reconstruction.
      This adjunctive treatment was successful in 16 cases. Overall, when used as a
      first-line treatment, thrombolysis was successful in 72% of cases. Success in
      this context includes those in which a further procedure was possible after
      thrombolysis. These groups included 20 occluded grafts in which thrombolysis
      played an important part in unblocking 13 (65%) of them. In a separate group of
      17 patients (24%) thrombolysis was given after failed angioplasty and was
      successful on 15 (88%) occasions. Local complications occurred in 17 patients.
      There were three deaths. There were no intra-cerebral haemorrhages. CONCLUSIONS:
      Thrombolysis alone can be used successfully. There is a large group in which
      thrombolysis can help to increase the success rate of interventional radiology.

PMID- 7633992
TI  - Arterial reconstruction for subclavian obstructive disease: a comparison of
      extrathoracic procedures.
AB  - OBJECTIVES: Comparison of the immediate and long-term results of three different
      extrathoracic arterial reconstruction procedures for subclavian obstructive
      disease. DESIGN: Retrospective analysis of 51 extrathoracic subclavian artery
      reconstructions in 49 patients performed in a single centre over an 18-year
      period (mean follow-up 64 months, range 3-192). METHODS: Carotid-subclavian
      bypass (CSB, n = 21), subclavian-carotid transposition (SCT, n = 21) and
      subclavian-subclavian or axillo-axillary cross-over bypass (COB, n = 9) was
      performed. Upper extremity ischaemic complaints were present in 45/49 patients
      (92%) and vertebrobasilar insufficiency in 25/49 patients (51%). Symptom relief,
      improvement of haemodynamic parameters and graft patency were compared. RESULTS:
      Operation time was significantly shorter (p < 0.001, t-test) in SCT (80 +/- 5
      min) compared to CSB (112 +/- 7 min) and COB (116 +/- 6 min). Symptom relief and
      improvement of haemodynamic parameters were similar for all groups. There were no
      differences in morbidity rate and there was no mortality. The cumulative patency
      of SCT was significantly better with 100% at 2, 5 and 10 years postoperatively
      compared to CSB (75.6%, 62.6% and 52.2%, respectively) (p < 0.005, log-rank test)
      and COB (76.5%, 63.7% and 63.7%, respectively) (p < 0.02, log-rank test). There
      was a tendency for a better patency in prosthetic grafts as compared to
      autologous vein grafts in CSB (NS, log-rank test). CONCLUSIONS: Satisfactory
      immediate and long-term results were obtained with all of the above techniques.
      When technically feasible, SCT is the procedure of choice for extrathoracic
      arterial reconstruction in subclavian obstructive disease.

PMID- 7633994
TI  - Photodynamic therapy in a cell culture model of human intimal hyperplasia.
AB  - OBJECTIVE: To investigate the effectiveness of photodynamic therapy (PDT) in
      eliminating proliferating vascular smooth muscle cells (VSMCs). This may have a
      potential role in reducing restenosis rates clinically. MATERIALS AND METHODS:
      Human VSMCs were successfully cultured from 15 long saphenous veins (SV) and
      seven restenotic lesions (RL) removed during revision coronary and peripheral
      vein graft surgery. Cultured VSMCs were incubated with photofrin at doses of 0-5
      micrograms/ml for 48 h, and then exposed to 4 J/cm2 of polychromatic light. Cell
      destruction was quantified by a colorimetric assay using 3-(4,5-dimethylthiazol-2
      yl)-2,5-diphenyltetrazolium bromide. RESULTS: Results are expressed as a mean
      percentage survival +/- standard error. Cells were minimally affected by either
      photofrin alone (SV: 95.5% +/- 5.3; RL: 119.8 +/- 4.8) or light alone (SV: 75.38%
      +/- 3.99; RL: 100.1 +/- 11.0). The combination of 2 micrograms/ml of photofrin
      and 4 J/cm2 of polychromatic light energy, i.e. PDT, was severely toxic to cells
      derived from saphenous veins (5.52% +/- 0.85) as well as cells derived from
      restenotic lesions (9.6 +/- 2.3). These doses are comparable to doses that can be
      achieved in vivo. CONCLUSION: PDT in the appropriate drug and light doses can
      eliminate human VSMCs, including those responsible for vascular restenosis.

PMID- 7633995
TI  - Impact of intermittent claudication on quality of life. The Scottish Vascular
      Audit Group.
AB  - OBJECTIVES: Surgical treatment of intermittent claudication is aimed primarily at
      improving quality of life, rather than survival. The aim of this study was to
      examine the impact of claudication on quality of life and the ability of surgeons
      to judge this. DESIGN AND MATERIALS: 201 claudicants rated their quality of life
      and completed an SF36 health status questionnaire prior to their first
      consultation. Following the consultation, the surgeons rated their perceptions of
      the patients' quality of life. CHIEF OUTCOME MEASURES: SF36 scores were compared
      with population norms. Multiple linear regression analysis determined the factors
      influencing quality of life. Agreement between surgeon and patient ratings of
      quality of life was expressed as a kappa coefficient. MAIN RESULTS: Compared to
      population norms, claudicants had significantly reduced quality of life in all
      respects. The severity of disease, as measured by stopping distance, was a
      significant predictor of general health, pain, vitality and physical and social
      parameters. Mental and emotional wellbeing were also reduced, but were not
      related to disease severity. The agreement between patient and surgeon
      assessments of quality of life was not high (k = 0.4). Patients had a higher
      perception of their quality of life than their surgeons. CONCLUSIONS:
      Intermittent claudication impairs quality of life in all respects. The type of
      treatment offered to patients should reflect their quality of life at
      presentation, but subjective assessments by surgeons may not be sufficiently
      accurate. Health status questionnaires have been used almost exclusively in
      research, but they may also be of use in clinical settings as an objective
      measure of quality of life.

PMID- 7633996
TI  - Current reflections of the vascular surgeon on the assessment and treatment of
      critical limb ischaemia.

PMID- 7633997
TI  - Percutaneous stenting of proximal subclavian artery occlusion.

PMID- 7633998
TI  - Acute infrarenal abdominal aortic dissection with secondary aneurysm formation in
      pregnancy.

PMID- 7633999
TI  - Isolated aneurysm of the dorsalis pedis artery.

PMID- 7634002
TI  - Infected false aneurysm at the site of peripheral balloon angioplasty.

PMID- 7634000
TI  - Primary sarcoma of an iliac artery aneurysm.

PMID- 7634001
TI  - Thigh embolisation in association with bilateral profunda femoris aneurysms.

PMID- 7634003
TI  - Inflammatory aneurysm of the abdominal aorta infected by Salmonella dublin.

PMID- 7634004
TI  - Occlusion of the femoral artery secondary to osteochondroma.

PMID- 7634005
TI  - Percutaneous treatment of anastomotic leak following elective aortic aneurysm
      repair.

PMID- 7634006
TI  - Mesenteric revascularisation.

PMID- 7634007
TI  - Fibrodysplasia.

PMID- 7634008
TI  - False aneurysms.

PMID- 7634009
TI  - Endothelial cells.

PMID- 7634011
TI  - Heterotopic ossification following TKA.

PMID- 7634012
TI  - The pullout strength and use of tibial interference screws during endoscopic ACL
      reconstruction surgery.
AB  - This article retrospectively reviews the last 89 ACL reconstructions done over
      the past 24 months by the senior author and also investigates the pullout
      strength of a 15-mm long interference screw in cadaveric knees. Results revealed
      that interference screw fixation at the tibial tunnel during endoscopic ACL
      reconstruction should almost always be possible by ensuring a tibial tunnel with
      adequate length, taking additional bone on the graft from the proximal tibia,
      twisting the graft, and possibly using a 15-mm interference screw.

PMID- 7634014
TI  - Meniscal repair using a flap of synovium. An experimental study in the dog.
AB  - The healing process of longitudinal lesions in the avascular region of the
      meniscus was investigated in 42 menisci from 21 dogs. A longitudinal incision was
      made in the avascular portion of the medial menisci of 21 dogs. In one knee, a
      flap of synovium was sutured into the wound, and in the other, the wound was
      sutured as a control. Animals were killed after 1 to 12 weeks, and the menisci
      were removed and examined by gross inspection, light microscopy, and
      microangiography. In the control knees, no healing had occurred. In 19 of 21
      knees in which a synovial pedicle was used, the suture site did not open at any
      of the postoperative weeks. The longitudinal lesion was repaired with
      fibrovascular tissue at 6 weeks, and the vessels over the femoral surface of the
      menisci and an inner portion of the menisci had reached the suture site. The
      healing of meniscal lesion occurred due to the use of the vascularized synovial
      pedicle flap and the neovascularization from the parameniscal area.

PMID- 7634013
TI  - Supracondylar femoral osteotomies for the correction of angular deformity about
      the knee in children. A follow-up study.
AB  - The results of 18 supracondylar osteotomies of the femur performed for angular
      deformity about the knee joint on 14 patients under the age of 18 years were
      reviewed. The mean follow-up was 46 months. Twelve of 18 osteotomies had a
      successful outcome. Six were considered failures due to recurrence of angular
      deformity despite bony union at the osteotomy site. Four of the six failures
      occurred in patients with metabolic bone disease. Special care needs to be taken
      when planning supracondylar osteotomies in patients with metabolic disease.

PMID- 7634015
TI  - Knee arthrodesis using a short locked intramedullary nail. A new technique.
AB  - This article reports on the use of a new intramedullary nail designed
      specifically for fixation of knee fusions. The nail is a short locked stainless
      steel nail that is inserted through a single anterior knee incision and uses an
      outrigger targeting rod to guide the insertion of the locking screws. The
      successful use of this technique is illustrated in two cases. The advantages of
      this nail compared with previously reported techniques of fixation for knee
      fusions are that the short locked nail avoids the second incision required for
      the insertion of long knee fusion nails, the bulkiness of the double plating
      technique in the relatively subcutaneous anterior knee area, and the difficulties
      inherent with the prolonged use of pins for external fixation.

PMID- 7634017
TI  - Bilateral discoid medial menisci. Case report.

PMID- 7634016
TI  - Indirect forces and patella fracture after anterior cruciate ligament
      reconstruction with the patellar ligament. Case report.
AB  - Patella fracture is either an infrequent or underreported complication after
      anterior cruciate ligament (ACL) reconstruction using a portion of the patellar
      ligament. Patella fracture pattern has been related to the mechanism of injury.
      Direct fractures resulting from impaction forces delivered to the patella are
      typically stellate or comminuted. Indirect fractures resulting from tensile
      stresses applied across the extensor mechanism typically are displaced transverse
      disruptions. After ACL reconstruction using a portion of the patellar ligament, Y
      shaped stellate fractures can occur. Fracture pattern seems related to the time
      elapsed since the harvest; stellate fractures occur following stumbles or slips
      without direct injury early in the postoperative period while transverse
      fractures occur late. This article describes two cases of patella stellate
      fractures that occurred in patients who underwent ACL reconstruction using
      patellar graft.

PMID- 7634018
TI  - Treatment of failed Hauser procedures via modified Maquet osteotomy. Case report.
AB  - Four cases of failed Hauser procedures were treated with an osteotomy of the
      patellar tendon insertion and distal realignment. The patellar tendon insertion
      site was moved as a large bond block and positioned in neutral alignment as well
      as anterior to its previous position, effectively creating a "modified Maquet
      effect." Proximal realignment was performed in one patient. Intraoperative
      assessment of patellar tracking enabled accurate determination of optimal
      position. The clinical findings and the operative approach are described. All
      four patients experienced significant improvement from ther preoperative status.

PMID- 7634019
TI  - Exercise-induced acute compartment syndrome of the thigh. Case report.

PMID- 7634020
TI  - Reflections.

PMID- 7634021
TI  - The "sagging rope sign" in avascular necrosis in children's hip diseases-
      confirmation by 3D CT studies.
AB  - Growth disturbance of the proximal femoral epiphysis and physis secondary to
      avascular necrosis (AVN) in a variety of children's hip disorders produces
      changes in the femoral head and neck that make radiographic interpretation
      difficult. The enlarged overhanging femoral head produces radiographic markings
      on the femoral neck which are sometimes confusing. These have sometimes been
      misinterpreted as growth arrest lines. Apley and Wientroub reintroduced Perkins'
      description of the "sagging rope" sign in AVN of the femoral head, and Clarke
      clarified that this puzzling radiographic transverse metaphyseal line overlying
      the femoral neck in fact represents the margin of the femoral head rather than a
      growth arrest line. Their report was made after studying plain and stereoscopic
      radiographs alone. Our review of 23 cases of femoral head AVN in children,
      documented by 3 dimensional computerized tomographic (3D CT) radiographs of the
      femoral head and pelvis, confirms Clarke's view of the nature of the "sagging
      rope" sign. These sophisticated radiographic studies provide new detail and
      understanding of head-neck relationship in AVN which allows better planning for
      surgical correction of hip disorders in children.

PMID- 7634022
TI  - Techniques for cell and tissue culture mechanostimulation: historical and
      contemporary design considerations.

PMID- 7634024
TI  - Differences in ligamenta flava among some mammals.
AB  - The ligamenta flava of the thoracolumbar spine of mammals with great spinal
      mobility have a larger content of elastin than in animals with little spinal
      motion. The elastin content is also higher in the ligamenta flava of mammals with
      arched backs and prolonged sitting posture than in nonsitting mammals with the
      vertebral column in the shape of a flat bow. The ligamentum flavum appears to be
      important; a) in the control of intervertebra movements, b) in providing
      intrinsic stability to the spine in the sitting and standing postures and c) in
      maintaining a smooth surface in the posterior wall of the spinal canal and neural
      foraminae.

PMID- 7634025
TI  - Mechanoreceptor endings of the cervical, thoracic, and lumbar spine.

PMID- 7634026
TI  - Proprioception in the anteriorly unstable knee.

PMID- 7634027
TI  - Morphological and biochemical effects of strenuous exercise on immature long
      bones.
AB  - To determine the effects of intense exercise on the growth of long bones in
      immature animals, young male white leghorn chickens were run five days per week
      starting at four weeks of age on motor-driven treadmills. Work intensity was
      determined on the basis of maximal oxygen consumption (VO2 max) with the exercise
      intensity maintained at 70-80 percent VO2 max. Young animals ran continuously for
      30 minutes, older animals 45 to 60 minutes each day. Runners and controls (10
      animals per group) were sacrificed at 8, 12, 14 and 20 weeks of age. The lengths
      of the femurs and tibiotarsus were significantly stunted at 8-, 12- and 14 weeks
      in the runners but had nearly recovered at 20 weeks of age. Both bones also
      demonstrated significantly decreased total cross-sectional areas in 8-, 12- and
      14 week-old runners as well as decreased cortical cross-sectional areas. The
      tibiotarsus also remained significantly smaller in the 20-week-old runners, but
      the femur had recovered in terms of radial growth. Intermolecular pyridinoline
      collagen crosslinks were identical in amount in the two groups with the femur
      collagen significantly less cross-linked than the tibiotarsus. The delayed growth
      of the exercised avian young bone is consistent with data obtained from children
      and young mammalian models. The osteogenic response to exercise that produces an
      increased bone mass in adult tissue appears either suppressed or overcome in
      young avian bone indicating that it may be erroneous to assume that data obtained
      from adult tissue are also applicable to young growing bone.

PMID- 7634028
TI  - The sensitivity of joint afferents to knee translation.
AB  - The cruciate ligaments contain mechanoreceptors which putatively contribute to
      knee function and dysfunction. However, the interpretation of studies showing
      neural responses to traction loads applied to the cat cranial cruciate ligament
      (CCL-analogous to the anterior cruciate ligament in humans) depends upon
      demonstrating that non-CCL periarticular receptors are not stimulated. We
      assessed the capability to rigidly fix the knee against traction loads applied to
      the feline CCL. The tibia and femur were fixed either with clamps or Steinmann
      pins. Motion of the bones was monitored with liquid metal strain gauges (LMSG)
      and the activity of the posterior articular nerve (PAN) was recorded while
      traction loads of up to 20-30 N were applied to the CCL. Joint afferents recorded
      from the PAN were insensitive to the CCL loads in the rigidly fixed preparation.
      Motion of the proximal tibia and distal femur was less than 100 micrometers for
      both methods of fixation, with neither method demonstrating more rigid fixation.
      In contrast, we observed vigorous discharges with focused light pressure on the
      capsule and under conditions allowing 200-500 micrometers of tibial displacement
      on the femur. This suggests that clinically undetectable instability may give
      rise to aberrant mechanoreceptor activity contributing to dysfunction.

PMID- 7634030
TI  - Rationale for classification of flexion vs extension strain in acute low back
      pain.

PMID- 7634029
TI  - Current status of walking orthoses for thoracic paraplegics.

PMID- 7634023
TI  - Development of the osteoblast phenotype: molecular mechanisms mediating
      osteoblast growth and differentiation.
AB  - The formation of bone tissue involves multiple activities of the osteoblast. The
      combined application of molecular, biochemical, histochemical and ultrastructural
      approaches has defined stages in the development of the osteoblast phenotype with
      each subpopulation of cells exhibiting unique morphologic and functional
      properties in relation to the ordered deposition of the mineralized bone
      extracellular matrix (ECM). Peak levels of expressed genes reflect a maturational
      sequence of osteoblast growth and differentiation characterized by three
      principal periods: proliferation, ECM maturation and mineralization. A plethora
      of new information in the past several years provides the basis for insight into
      molecular mechanisms regulating the development and activities of differentiating
      osteoblasts. These new concepts will be discussed within the context of
      understanding cellular responses of bone tissue. To be considered are the
      following: 1) maturational stages of the osteoblast reflected by the selective
      expression of transcription factors (e.g., oncogenes, cyclins, homeodomain
      proteins) and phenotypic genes that provide signals for differentiation through
      the osteoblast lineage; 2) role of the extracellular matrix in mediating
      osteoblast growth and differentiation; 3) osteoblast stage specific responses to
      physiologic mediators (e.g., growth factors and hormones); 4) the developmentally
      regulated expression and selective responses of osteoblast phenotypic genes are
      supported by cooperative, synergistic and/or antagonistic activities at multiple
      basal and enhancer or suppressor sequences in gene promoters; and 5) deregulation
      of these control mechanisms in transformed osteoblasts and osteosarcoma cells.

PMID- 7634031
TI  - Acetabular fractures classification of Letournel and Judet--a systematic
      approach.
AB  - After a background understanding of the classification of Judet and Letournel and
      the radiographic anatomy of the pelvis, the majority of acetabular fractures are
      readily classified by utilizing the steps as outlined above. We feel that a
      systematic, stepwise approach to classifying acetabular fractures into larger
      groups and then subclassifying these groups will help simplify the application of
      the Letournel and Judet classification. Try using this method, and your ability
      to classify these fractures will improve.

PMID- 7634032
TI  - Rehabilitation following anterior cruciate ligament reconstruction: what do we
      really know?

PMID- 7634033
TI  - An articulated ankle external fixation system that can be aligned with the ankle
      axis.
AB  - Aligning an articulated ankle external fixator with the ankle axis located using
      a mechanical axis finder has been shown to preserve normal ankle joint kinematics
      while the fixed hinge device is attached. However, several problems exist
      preventing the clinical application of this finding for fractures of the tibial
      plafond. We initiated a series of studies to resolve these issues. First, the
      accuracy of the mechanical axis finder in biological systems was quantified by
      comparing it to that of a computationally derived helical axis. Second, a
      prototype fixator design was developed in the biomechanics lab to increase the
      versatility of intraoperative fixator placement. Finally, a radiographic method
      of locating the ankle axis was developed which is based on talar morphology
      independent of the fractured tibia. The prototype fixator has been accurately
      aligned along the ankle axis in cadaveric specimens using this method. Open
      reduction and internal fixation (ORIF) is the accepted method of treatment for
      tibial plafond fractures. It holds the advantage of sufficient fracture fixation
      to permit early joint motion. Good results have been reported using this method,
      but some authors have reported complication rates up to 50%. The wide surgical
      approaches required, in conjunction with preexisting soft tissue injury, are
      thought to significantly increase the risk of soft tissue complications. In
      response to these problems, many investigators are beginning to utilize external
      fixation as an alternate treatment modality. One external fixation system which
      has shown particularly good results is a monolateral cross-ankle articulated
      fixator (Orthofix SRL., Verona, Italy) which allows motion at the ankle joint as
      the plafond fracture is healing (Figure 1).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7634034
TI  - The leather ankle lacer.
AB  - The purpose of this study was to evaluate the efficacy of a leather ankle lacer
      for treating painful problems of the ankle and hindfoot. The evaluation involved
      patient self assessment, clinical examination and radiographic determination of
      the effectiveness of the ankle lacer. Overall, patients had moderate pain relief
      with significant but not complete restriction of motion. Based on this study and
      our clinical experience, we find the leather ankle lacer to be a compliant and
      comfortable treatment strategy for patients with painful ankle and hindfoot
      problems who desire some retained motion.

PMID- 7634037
TI  - Regional lidocaine anesthesia without exsanguination for outpatient management of
      upper extremity fractures.
AB  - The use of small dose intravenous lidocaine without exsanguination for upper
      extremity fractures in children and adults is described. A twenty-plus year
      experience with this technique in the outpatient setting has shown it to be
      effective and safe. Attention to detail is essential and inadvertent tourniquet
      release must be avoided.

PMID- 7634035
TI  - The management of severe avascular necrosis following slipped capital femoral
      epiphysis by transtrochanteric rotational osteotomy. Results of successful
      treatment in two cases with longterm follow-up.
AB  - We present two cases of unstable slipped capital femoral epiphysis complicated by
      avascular necrosis that were successfully treated with transtrochanteric anterior
      rotational osteotomy. These two cases both had severe avascular necrosis and were
      felt to be unsalvageable. We recommend this surgical technique as a viable
      alternative to other forms of treatment in this selected patient population.

PMID- 7634036
TI  - Septic knee from Ilizarov transfixation tibial pin.

PMID- 7634038
TI  - Spontaneous rupture of ulnar-sided digital flexor tendons: don't forget the
      hamate.

PMID- 7634039
TI  - A stress fracture of the scapular body in a child.

PMID- 7634041
TI  - The response of the flexion-relaxation phenomenon in the low back to loading.
AB  - Fick hypothesized in 1911 that the erector spinae muscles are not active when the
      trunk is in the fully flexed position. This effect was later called the flexion
      relaxation phenomenon (FRP) and is believed to be the result of the ligaments and
      other passive elements of the spine taking over the load of the muscles. This
      study examined the effect of loading on the EMG activity of five males and five
      females during postures of standing at 45 degrees, 90 degrees, and full flexion.
      The results showed major differences in the relationship between the
      electromyographic signal (EMG) of the erector spinae and loading for the four
      postures. The erector spinae muscles did not activate in positions of full
      flexion (or even 90 degrees for some subjects) for loading as high as 50% of
      their maximum voluntary contraction, suggesting that alternative muscles are
      being activated and that the passive tissues may be put under higher loads than
      originally thought in these positions. The results suggested that the FRP could
      be used as a biofeedback tool to illustrate to workers that their muscles are not
      turning on in the fully flexed positions, and therefore, these positions should
      be avoided.

PMID- 7634040
TI  - The fates of illustrious bones.

PMID- 7634044
TI  - Primary cemented total hip arthroplasty: five to twelve year clinical and
      radiographic follow-up.
AB  - A retrospective clinical and roentgenographic study was completed on 131 primary
      cemented total hip arthroplasties with a minimum of five years follow-up (mean,
      seven years; range, five to twelve years). Second generation cement technique
      including plugging of the medullary canal, cement gun filling, and pressurization
      of the canal was used. Acetabular cement was also pressurized. The total
      mechanical failure rate of the acetabular components was 18.4% compared to that
      of the femoral components which was 3.1%. There was a significantly higher
      incidence of acetabular component failure in rheumatoid arthritis patients
      (38.9%) compared to a preoperative diagnosis of primary osteoarthritis (14.1%) (p
      = 0.013). Yet there were no rheumatoid arthritis patients in the femoral
      component revision group. There were no differences in revision rates for metal
      backed versus nonmetal-backed cups (p = 0.113). The average thickness of the
      proximal medial cement mantle was 2.8 millimeters in the loosening group and 5.4
      millimeters in the nonloosening group (p = 0.333). All failures occurred in those
      patients whose proximal medial cement mantle was less than five millimeters. The
      authors strongly endorse the use of hybrid total hip arthroplasty and emphasize
      the need for meticulous surgical technique especially in obtaining a cement
      mantle of sufficient thickness in the proximal medial aspect of the femur.

PMID- 7634045
TI  - The surgical approach to total hip arthroplasty: complications and utility of a
      modified direct lateral approach.

PMID- 7634042
TI  - Activity vs. rest in the treatment of bone, soft tissue and joint injuries.
AB  - One of the most important advances in the treatment of musculoskeletal injuries
      has come from understanding that controlled early resumption of activity can
      promote restoration of function, and that treatment of injuries with prolonged
      rest may delay recovery and adversely affect normal tissues. In the last decade
      of the nineteenth century two widely respected orthopaedists with extensive
      clinical experience strongly advocated opposing treatments of musculoskeletal
      injuries. Hugh Owen Thomas in Liverpool believed that enforced, uninterrupted
      prolonged rest produced the best results. He noted that movement of injured
      tissues increased inflammation, and that, "It would indeed be as reasonable to
      attempt to cure a fever patient by kicking him out of bed, as to benefit joint
      disease by a wriggling at the articulation." Just Lucas-Championnier in Paris
      took the opposite position. He argued that early controlled active motion
      accelerated restoration of function, although he noted that mobility had to be
      given in limited doses. In general, Thomas' views met with greater acceptance in
      the early part of this century, but experimental studies of the last several
      decades generally support Lucas-Championneir. They confirm and help explain the
      deleterious effects of prolonged rest and the beneficial effects of activity on
      the musculoskeletal tissues. They have shown that maintenance of normal bone,
      tendon and ligament, articular cartilage and muscle structure and composition
      require repetitive use, and that changes in the patterns of tissue loading can
      strengthen or weaken normal tissues. Although all the musculoskeletal tissues can
      respond to repetitive loading, they vary in the magnitude and type of response to
      specific patterns of activity. Furthermore, their responsiveness may decline with
      increasing age. Skeletal muscle and bone demonstrate the most apparent response
      to changes in activity in individuals of any age. Cartilage and dense fibrous
      tissues also can respond to loading, but the responses are more difficult to
      measure. The effects of loading on injured tissues have been less extensively
      studied, but the available evidence indicates that repair tissues respond to
      loading and, like immature normal tissues, may be more sensitive to cyclic
      loading and motion than mature normal tissues. However, early motion and loading
      of injured tissues is not without risks. Premature or excessive loading and
      motion of repair tissue can inhibit or stop repair. Unfortunately, the optimal
      methods of facilitating healing by early application of loading and motion have
      not been defined.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7634046
TI  - Our experience with dual energy X-ray absorptiometry (DEXA) and the Wisconsin
      Hip.

PMID- 7634043
TI  - Computer-aided preoperative planning in knee osteotomy.
AB  - It has been demonstrated that osteoarthritis (OA) is activity related and may
      worsen when joint contact stress becomes excessive due to overloading. Hence,
      joint alignment and loading are considered to be the key biomechanical
      determinants for OA. The initiation of pathologic changes in the knee has been
      described by the mechanism termed, "vicious cycle" in which joint axial
      malalignment creates excessive stresses to the localized joint
      cartilage/subchondral bone regions and the surrounding soft tissue which in turn
      produces more laxity and joint deformity and thus repeats the cyclic degradation
      mechanism. If this degenerative cycle can be broken with joint alignment surgery
      such as osteotomy, a procedure to realign the knee joint and thus redistribute
      joint forces applied to each compartment, performed properly and at the
      appropriate time, the osteoarthritic disease process can be decelerated and even
      reversed. The main goals of this paper are to emphasize the importance of
      accurate preoperative planning for osteotomy in order to properly correct joint
      alignment, and to justify the application of an existing computer program, OASIS
      (Osteotomy Analysis and Simulation Software) using plain radiographs to perform
      appropriate surgical planning. Normal subjects and knee osteotomy patients were
      studied to establish a database for the purpose of establishing the utility and
      efficacy of the presently proposed concept. We wish to rationalize knee osteotomy
      as a preferred and cost-effective treatment for patients with early symptoms of
      OA in the knee. This paper presents a new concept of preoperative planning for
      knee osteotomy based on the underlying etiology of the disease and biomechanical
      viewpoint with strong emphasis on surgical treatment rationales. The established
      principles in this paper can be applied to other joints of the body and will help
      implement preventive measures and other non-surgical means to manage patients
      with axial malalignment or early degenerative changes.

PMID- 7634047
TI  - Multiple drug resistance in osteosarcoma.

PMID- 7634048
TI  - The Registry of Bone Sarcoma. A history.

PMID- 7634049
TI  - The surgical treatment of congenital spine deformity: general principles and
      helpful hints.

PMID- 7634050
TI  - Chiropractic manipulation: an historical perspective.

PMID- 7634052
TI  - A dermatosis resembling juvenile cellulitis in an adult dog.
AB  - A two-year-old, female Lhasa apso presented with an acute onset of fever,
      anorexia, lethargy, prescapular and mandibular lymphadenopathy, otitis externa,
      and a dermatitis involving the perioral and auricular skin. Histopathological
      examination of affected skin and a mandibular lymph node was diagnostic for
      juvenile cellulitis. Extensive hematological, serological, urine, skin, and fecal
      testing together with special staining, immunofluorescence, and electron
      microscopic examination of skin and lymph node biopsies failed to reveal an
      underlying etiology. After 15 weeks the condition resolved completely. This
      represents the first adult case of a dermatosis fitting the clinical,
      histological, and clinicopathological description ascribed to juvenile
      cellulitis.

PMID- 7634051
TI  - Symmetrical lupoid onychodystrophy in dogs: a retrospective analysis of 18 cases
      (1989-1993).
AB  - A unique, symmetrical onychodystrophy is described in 18 dogs. A rather sudden
      onset of onychomadesis is followed by chronic onychodystrophy affecting all
      claws. Pain and lameness are recognized in half of the patients, but the dogs are
      healthy otherwise. Histopathologically, this disorder is characterized by
      hydropic and lichenoid interface dermatitis. Nine dogs were treated with a
      commercial, fatty-acid supplement and had good-to-excellent responses. Due to the
      clinicopathological characteristics of this disorder, the authors propose the
      name "symmetrical lupoid onychodystrophy."

PMID- 7634053
TI  - Microphakia associated with lens luxation in the cat.
AB  - Congenital defects of the lens are rare in the cat. In this report, two unrelated
      Siamese kittens, a four-month-old male and a six-month-old female, with
      microphakia are presented. Abnormally small lenses were associated with
      elongation and rupture of the ciliary processes, leading to lens subluxations and
      subsequent anterior luxations. To the authors' knowledge, this condition has been
      reported only once previously.

PMID- 7634054
TI  - Disseminated Mycobacterium avium--intracellulare complex infection in a miniature
      schnauzer.
AB  - A two-year-old, spayed female, miniature schnauzer was evaluated for respiratory
      distress associated with a compressive cervical mass. Generalized mycobacterial
      infection was diagnosed from aspirates of several enlarged lymph nodes. Tissue
      specimens further identified Mycobacterium avium--intracellulare using polymerase
      chain reaction followed by nucleic acid hybridization. Treatment with
      enrofloxacin, clofazamine, rifampin, and interferon did not result in long-term
      success.

PMID- 7634055
TI  - Traumatic hemoperitoneum in 28 cases: a retrospective review.
AB  - This study was conducted to evaluate and describe presenting clinical signs,
      course, management, and outcome of small animal patients that suffered severe
      traumatic hemoperitoneum. The medical records of 28 blunt trauma patients
      diagnosed as having hemoperitoneum and requiring the transfusion of blood
      products for stabilization were analyzed. The survival rate was 16/28 (57%). Six
      patients died from natural causes, and six patients were euthanized. Euthanized
      patients were not considered for the analysis of outcome. The survival rates for
      six animals that had surgical intervention and 16 animals that were treated
      medically were 67% and 75%, respectively. Statistically, larger animals had a
      better prognosis (p less than 0.05, unpaired t-test) for survival. Presenting
      clinical signs, packed cell volume (PCV), peripheral pulse rate, effusion PCV,
      site of intra-abdominal hemorrhage, and age were not found to correlate
      statistically with survival nor with the decision to perform an abdominal
      exploratory.

PMID- 7634056
TI  - Canine distemper infection in pet dogs: I. Surveillance in Indiana during a
      suspected outbreak.
AB  - A mail survey of 613 private veterinary practices in Indiana was conducted to
      determine the prevalence of canine distemper infection in Indiana during 1991 and
      1992 and to compare the prevalence in three geographic regions. Of the practices
      that were contacted, 223 (37%) responded. Canine distemper had been diagnosed by
      150 (67%) of the 223 practices. The period prevalence increased significantly
      from 11.1 to 16.9 cases per 10,000 dog visits. Surveillance of private veterinary
      practices may be useful to confirm suspected outbreaks of diseases in companion
      animals.

PMID- 7634057
TI  - Canine distemper infection in pet dogs: II. A case-control study of risk factors
      during a suspected outbreak in Indiana.
AB  - The epidemiologic features of an outbreak of canine distemper during 1992 and
      1993 in pet dogs in Indiana are described. Risk factors for disease were
      characterized using hospital records of private veterinary practitioners. The
      risk of disease for purebred dogs was 85% lower than the risk of disease for
      mixed-breed dogs. Lack of vaccination was associated with a 350-fold increase in
      the risk of canine distemper, and 93.8% of all cases could be attributed to the
      lack of vaccination. For many of the owners, the cost of medical treatment
      exceeded the cost of a vaccination program.

PMID- 7634058
TI  - A quantitative study of the effects of Tribrissen on canine tear production.
AB  - The effect of trimethoprim-sulfadiazinea on Schirmer tear test (STT) values was
      studied in a population of dogs treated with the drug for a variety of medical
      and postsurgical conditions. The objectives of the study were to determine the
      incidence of keratoconjunctivitis sicca (KCS) secondary to trimethoprim
      sulfadiazine therapy; to determine if such incidence was related to dose,
      duration, or both; and to identify any other factors that increased patient risk.
      The package insert accompanying Tribrissen states that "Dogs can tolerate up to
      ten times the recommended therapeutic dose without exhibiting ill effects." The
      results of this study indicated a 15.2% (5/33) incidence of KCS in the population
      of treated dogs.

PMID- 7634059
TI  - Central amaurosis induced by an intraocular, posttraumatic fibrosarcoma in a cat.
AB  - A 12-year-old, castrated male, domestic shorthair cat with a previous penetrating
      trauma to the left globe which progressed to a phthisical eye presented for acute
      blindness. Ophthalmic examination and electroretinography of the right eye were
      found to be normal. Following euthanasia, gross and microscopic examinations were
      completed. A left intraocular, posttraumatic fibrosarcoma with extension to the
      optic nerve and chiasm and induced right optic nerve fiber degeneration at the
      optic chiasm with necrosis leading to central amaurosis were diagnosed.

PMID- 7634060
TI  - Efficacy of daily amitraz therapy for refractory, generalized demodicosis in
      dogs: two independent studies.
AB  - In two independent studies, 0.125% amitraz solution applied half-body daily was
      found 73% effective in curing dogs with demodicosis previously refractory to
      biweekly or weekly amitraz treatments. Thirteen of the 16 cases that resolved did
      so after one course of treatment which ranged from four weeks to five months in
      duration. The other three cases initially relapsed but then were cured after they
      were re-treated. All cases deemed cured, including those that initially relapsed,
      were followed for at least one year after their last treatment.

PMID- 7634062
TI  - Virucidal efficacy of the newer quaternary ammonium compounds.
AB  - The virucidal activity of several disinfectants containing newer generation
      quaternary ammonium compounds (QACs) as their active ingredients was evaluated.
      Disinfectants were used at the manufacturers' recommended dilutions with isolates
      of feline herpesvirus, feline calicivirus, and canine parvovirus, and a contact
      time of 10 minutes at room temperature. Detoxification of virus/disinfectant
      solutions was done by dialysis prior to virus assay in cell cultures. Two of four
      disinfectants completely inactivated feline herpesvirus, and two significantly
      reduced the titer of this virus. None of the disinfectants that were tested
      completely inactivated feline calicivirus. Canine parvovirus was not inactivated
      significantly by any of the QAC disinfectants. Sodium hypochlorite completely
      inactivated all viruses.

PMID- 7634061
TI  - Evaluation of topical therapies for the treatment of dermatophyte-infected hairs
      from dogs and cats.
AB  - Seven commonly used, topical antifungal products (i.e., lime sulfur,
      chlorhexidine, captan, povidone-iodine, sodium hypochlorite, and enilconazole
      solutions, and ketoconazole shampoo) were evaluated for their antifungal activity
      on Microsporum canis-infected hairs from dogs and cats in an in vitro study.
      Hairs were soaked or shampooed in each product for five minutes twice a week for
      four weeks. Of the seven products used in this study, lime sulfur and
      enilconazole solutions were superior in inhibiting fungal growth; no growth
      occurred on fungal cultures after two treatments with either product.
      Chlorhexidine and povidone iodine solutions were effective after four treatments,
      and sodium hypochlorite solution and ketoconazole shampoo inhibited fungal growth
      after eight treatments. Captan did not inhibit fungal growth during the test
      period.

PMID- 7634063
TI  - Control by protein phosphorylation.

PMID- 7634064
TI  - F1-ATPase in a spin.

PMID- 7634065
TI  - Advancing in a dynamic field.

PMID- 7634066
TI  - Linus Pauling. 1901-1994.

PMID- 7634067
TI  - Antagonist design through forced electrostatic mismatch.

PMID- 7634069
TI  - Picture story. Being direct.

PMID- 7634068
TI  - Nucleotide binding in beta alpha beta--beta alpha beta topologies.

PMID- 7634070
TI  - Picture story. Helping along peptide production.

PMID- 7634071
TI  - Parallel evolution in two homologues of phosphorylase.
AB  - The structure of the unphosphorylated, inactive form of yeast glycogen
      phosphorylase has been determined to a resolution of 2.6 A. The structure is
      similar to the phosphorylated, active form of muscle phosphorylase in the
      orientations of the subunits and catalytic residues, but resembles the inactive
      muscle enzyme in the closed, or substrate excluding, orientation of the two
      domains. Part of the unique yeast amino-terminal extension of 40 residues binds
      near the catalytic site of the second subunit in the homodimer, preventing the
      domain movement required for substrate access. Phosphorylation may displace the
      amino terminus from the active site, allowing the domains to separate.

PMID- 7634072
TI  - Crystallographic observation of a trapped tetrahedral intermediate in a
      metalloenzyme.
AB  - Formation of tetrahedral transition intermediates is a key step in many enzyme
      catalyzed reactions. Much of our understanding of these and other intermediates,
      at the atomic level, has come from crystallographic studies of very few enzymes
      with bound, synthetic, transition-state analogues. Here we present the structure
      of adenosine deaminase, a zinc-metalloenzyme critical in both purine metabolism
      and development of the lymphoid system, having performed a stereospecific
      hydroxide addition to the C6 of inosine. This addition causes the O6 oxygen of
      inosine to assume an orientation analogous to the position of the amino leaving
      group of the tetrahedral intermediate in the enzyme-catalyzed hydrolytic
      deamination of adenosine to inosine.

PMID- 7634073
TI  - Crystal structure of trichosanthin-NADPH complex at 1.7 A resolution reveals
      active-site architecture.
AB  - We describe here the crystal structure of the trichosanthin-NADPH complex
      determined at a resolution of 1.7 A. The adenine base stacks between Tyr 70 and
      Tyr 111. Arg 163, Glu 160 and Tyr 70 form hydrogen bonds to N(3), O(3') and,
      through a water molecule, to N(9) of adenosine, respectively. This is the first
      high resolution structure of a complex between a ribosome-inactivating protein
      and a substrate analogue, in which the electron density of the N-glycosidic bond
      is well defined and the preassociated water, thought to be responsible for
      hydrolyzing the N-C bond, is also explicitly elucidated.

PMID- 7634074
TI  - Photolysis-induced structural changes in single crystals of carbonmonoxy
      myoglobin at 40 K.
AB  - Myoglobin's reversible binding of oxygen is a model for studies of protein
      control of ligand binding and discrimination. Protein relaxation and geminate
      ligand rebinding subsequent to ligand photodissociation have been studied
      extensively by a variety of techniques. The ps to ns time scales for these
      processes are still much shorter than the ms time resolution of X-ray diffraction
      experiments, but it may be possible to trap these intermediates at low
      temperatures. We report here an X-ray diffraction investigation of structural
      changes induced by photolysis of carbonmonoxy myoglobin crystals at 40 K. Our
      results provide a structural basis for the interpretation of ambient and low
      temperature spectroscopic observations and molecular dynamics simulations of the
      ligand photodissociation and binding processes in haem proteins.

PMID- 7634075
TI  - Restored heptad pattern continuity does not alter the folding of a four-alpha
      helix bundle.
AB  - The sequences of alpha-helical coiled-coils and bundles are characterized by a
      specific pattern of hydrophobic and hydrophilic residues which is repeated every
      seven residues. Highly conserved breaks in this pattern frequently occur in
      segments of otherwise continuous heptad substructures. The hairpin bend of the
      ROP protein coincides with such a break and provides a model system for the study
      of the structural effects induced by heptad discontinuities. The structure of a
      ROP mutant which re-establishes a continuous heptad pattern, shows insignificant
      changes relative to the wild-type protein, as is also reflected in its
      conformational stability, spectroscopic properties and unfolding behaviour. Thus,
      formation of alpha-alpha-hairpin bends may occur both in the presence and absence
      of heptad breaks.

PMID- 7634076
TI  - The structure of Bacillus subtilis pectate lyase in complex with calcium.
AB  - We have solved the structure of the Bacillus subtilis pectate lyase (BsPel) in
      complex with calcium. The structure consists of a parallel beta-helix domain and
      a loop region. The alpha L-bounded beta-strand seen in BsPel is a new element of
      protein structure and its frequent occurrence suggests it is an important
      characteristic of the parallel beta-helix. A pronounced cleft is formed between
      the loops and the parallel beta-helix domain and we propose that this is the
      active site cleft. Calcium, essential for the activity of the enzyme, binds at
      the bottom of this cleft and an arginine residue close to the calcium, which is
      conserved across all pectin and pectate lyases, may be involved in catalysis.

PMID- 7634077
TI  - The structure of avian eye lens delta-crystallin reveals a new fold for a
      superfamily of oligomeric enzymes.
AB  - The crystal structure of turkey delta-crystallin, a principal soluble components
      of the avian lens, has been determined to a resolution of 2.5 A. It is a
      tetramer, of 200,000 M(r), with 222 symmetry. The subunit has a new fold composed
      of three mainly alpha-helical domains. One domain is a bundle of five long
      helices which forms a 20-helix bundle at the core of the tetramer. delta
      crystallin shares approximately 90% sequence identity with the enzyme
      argininosuccinate lyase (EC 4.3.2.1), indicating that it is an example of a
      'hijacked' enzyme. It is also distantly related to the class II fumarases,
      aspartases, adenylosuccinases and 3-carboxy-cis,cis-muconate lactonising enzyme.
      The structure reveals a putative active-site cleft which is located on the
      boundary between three subunits of the tetramer. This is the first three
      dimensional structure of a representative of this superfamily of enzymes.

PMID- 7634078
TI  - Prediction of new serine proteinase inhibitors.
AB  - We describe here the use of a rapid computational method to predict the relative
      binding strengths of a series of small-molecule ligands for the serine proteinase
      trypsin. Flexible molecular models of the ligands were docked to the proteinase
      using an all-atom potential set, without cutoff limits for the non-bonded and
      electrostatic energies. The binding-strength calculation is done directly in
      terms of a molecular mechanics potential. The binding of eighteen different
      compounds, including non-binding controls, has been successfully predicted. The
      measured Ki is correlated with the predicted energy. The correctness of the
      theoretical calculations is demonstrated with both kinetics measurements and X
      ray structure determination of six enzyme-inhibitor complexes.

PMID- 7634079
TI  - Mediating intracellular communication.

PMID- 7634080
TI  - Casting a cold eye over myoglobin.

PMID- 7634081
TI  - Probing G-protein function.

PMID- 7634082
TI  - More meanders and sandwiches.

PMID- 7634083
TI  - A tale of two synthetases.

PMID- 7634084
TI  - Role of linker histones in extended chromatin fibre structure.

PMID- 7634086
TI  - Critical elements in proteasome assembly.
AB  - Coexpression of both subunits of the Thermoplasma proteasome in Escherichia coli
      yields fully assembled and proteolytically active proteasomes. Post-translational
      processing of the beta-subunit occurs in E. coli as it does in Thermoplasma.
      Coexpression of the alpha-subunit and the beta delta pro-subunit, a mutant beta
      subunit lacking the propeptide, also yields fully assembled and active
      proteasomes. This indicates that the beta-propeptide is not essential for the
      folding and assembly of Thermoplasma proteasomes. Separately expressed alpha
      subunits assemble into heptameric rings indistinguishable from the terminal rings
      of a proteasome. Mutational analysis shows that the amino terminus, which is
      highly conserved in all proteasomal alpha-type proteins, is essential for
      assembly. In the absence of alpha-subunits the beta-subunits are monomeric and
      post-translational processing of the beta-propeptide does not occur.

PMID- 7634087
TI  - Biochemical analysis of the transducin-phosphodiesterase interaction.
AB  - In vertebrate rod cells, the activated alpha-subunit of rod transducin interacts
      with the gamma (regulatory) subunits of phosphodiesterase to disinhibit the
      catalytic subunits. A 22-amino acid long region of rod transducin involved in
      phosphodiesterase activation has recently been identified. We have used peptides
      from this region of rod transducin and from several other G protein alpha
      subunits to study the nature and specificity of the G protein alpha-effector
      interaction. Although peptides derived from rod transducin, cone transducin and
      gustducin are similar, only the rod peptide is capable of activating rod
      phosphodiesterase. Using substituted peptides we have identified five residues on
      one exposed face of rod transducin as important to phosphodiesterase activation.
      These results disagree with previous models which propose that loop regions of
      rod transducin interact with phosphodiesterase gamma.

PMID- 7634085
TI  - Picture story. If the coat fits....

PMID- 7634088
TI  - Crystal structure of the pleckstrin homology domain from dynamin.
AB  - The pleckstrin homology (PH) domain is a conserved module present in many signal
      transducing and cytoskeletal proteins. Here we report the 2.8 A crystal structure
      of the PH domain from dynamin. This domain consists of seven beta-strands forming
      two roughly orthogonal antiparallel beta-sheets terminating with an amphipathic
      alpha-helix. The structure also reveals a non-covalent dimeric association of the
      PH domain and a hydrophobic pocket surrounded by a charged rim. The dynamin PH
      domain structure is discussed in relation to its potential role in mediating
      interactions between proteins.

PMID- 7634089
TI  - Human mannose-binding protein carbohydrate recognition domain trimerizes through
      a triple alpha-helical coiled-coil.
AB  - Human mannose-binding protein is a hexamer of trimers with each subunit
      consisting of an amino-terminal region rich in cysteine, 19 collagen repeats, a
      'neck', and a carbohydrate recognition domain that requires calcium to bind
      ligand. A 148-residue peptide, consisting of the 'neck' and carbohydrate
      recognition domains forms trimers in solution and in crystals. The structure of
      this trimeric peptide has been determined in two different crystal forms. The
      'neck' forms a triple alpha-helical coiled-coil. Each alpha-helix interacts with
      a neighbouring carbohydrate recognition domain. The spatial arrangement of the
      carbohydrate recognition domains suggest how MBP trimers form the basic
      recognition unit for branched oligosaccharides on microorganisms.

PMID- 7634090
TI  - Trifluoperazine-induced conformational change in Ca(2+)-calmodulin.
AB  - Here we show that, as a consequence of binding the drug trifluoperazine, a major
      conformational movement occurs in Ca(2+)-calmodulin (CaM). The tertiary structure
      changes from an elongated dumb-bell, with exposed hydrophobic surfaces, to a
      compact globular form which can no longer interact with its target enzymes. It is
      likely that inactivation of Ca(2+)-CaM by trifluoperazine is due to this major
      tertiary-structural alteration in Ca(2+)-CaM, which is initiated and stabilized
      by drug binding. This conformational change is similar to that which occurs on
      the binding of Ca(2+)-CaM to target peptides. Two hydrophobic binding pockets,
      created by amino acid residues adjacent to Ca(2+)-coordinating residues, form the
      key recognition sites on Ca(2+)-CaM for both inhibitors and target enzymes.

PMID- 7634091
TI  - Three-dimensional structure of the RGD-containing neurotoxin homologue
      dendroaspin.
AB  - Dendroaspin is a short chain neurotoxin homologue from the venom of Elapidae
      snakes, which lacks neurotoxicity. Unlike neurotoxins, it contains an Arg-Gly-Asp
      (RGD)-motif and functions as an inhibitor of platelet aggregation and platelet
      adhesion with comparable potency to the disintegrins from the venoms of
      Viperidae. We have determined the structure of dendroaspin in solution using NMR
      spectroscopy. The structure contains a core similar to that of short chain
      neurotoxins, but with a novel arrangement of loops and a solvent-exposed RGD
      motif. Dendroaspin is thus an integrin antagonist with a well defined fold
      different from that of the disintegrins, based on the neurotoxin scaffold.

PMID- 7634092
TI  - Solution structure and DNA-binding properties of a thermostable protein from the
      archaeon Sulfolobus solfataricus.
AB  - The archaeon Sulfolobus solfataricus expresses large amounts of a small basic
      protein, Sso7d, which was previously identified as a DNA-binding protein possibly
      involved in compaction of DNA. We have determined the solution structure of
      Sso7d. The protein consists of a triple-stranded anti-parallel beta-sheet onto
      which an orthogonal double-stranded beta-sheet is packed. This topology is very
      similar to that found in eukaryotic Src homology-3 (SH3) domains. Sso7d binds
      strongly (Kd < 10 microM) to double-stranded DNA and protects it from thermal
      denaturation. In addition, we note that epsilon-mono-methylation of lysine side
      chains of Sso7d is governed by cell growth temperatures, suggesting that
      methylation is related to the heat-shock response.

PMID- 7634093
TI  - Some like it hot.

PMID- 7634094
TI  - Grease pit chemistry exposed.

PMID- 7634095
TI  - Professor Dorothy Hodgkin, OM, FRS. 1910-1994.

PMID- 7634096
TI  - A single methyl group prevents the mischarging of a tRNA.

PMID- 7634097
TI  - Picture story. The results of thought and resolution.

PMID- 7634098
TI  - A short linear peptide that folds into a native stable beta-hairpin in aqueous
      solution.
AB  - The conformational properties of a 16 residue peptide, corresponding to the
      second beta-hairpin of the B1 domain of protein G, have been studied by nuclear
      magnetic resonance spectroscopy (NMR). This fragment is monomeric under our
      experimental conditions and in pure water adopts a population containing up to
      40% native-like beta-hairpin structure. The detection by NMR of a native-like
      beta-hairpin in aqueous solution, reported here for the first time, indicates
      that these structural elements may have an important role in the early steps of
      protein folding. It also provides a good model to study in detail the sequence
      determinants of beta-hairpin structure stability, as has been done with alpha
      helices.

PMID- 7634099
TI  - Structure of a pertussis toxin-sugar complex as a model for receptor binding.
AB  - Pertussis toxin is an exotoxin from the bacterium Bordetella pertussis which is
      important the pathogenesis of whooping cough and the generation of a protective
      immune response. The diverse biological activities of the toxin depend on its
      ability to recognize carbohydrate-containing receptors on a wide variety of
      eukaryotic cells. We present here the crystal structure of pertussis toxin
      complexed with a soluble oligosaccharide from transferrin. Binding sites for the
      terminal sialic acid-galactose moiety are revealed on both subunits S2 and S3 of
      the B-oligomer. Identification of amino acid residues involved in receptor
      binding will improve the design of genetically inactivated toxins for use in new
      acellular whooping cough vaccines.

PMID- 7634100
TI  - Solution structure of the DNA-binding domain of Drosophila heat shock
      transcription factor.
AB  - The solution structure of the DNA-binding domain of the Drosophila heat shock
      transcription factor, as determined by multidimensional multinuclear NMR,
      resembles that of the helix-turn-helix class of DNA-binding proteins. The domain
      comprises a four-stranded antiparallel beta-sheet, packed against a three-helix
      bundle. The second helix is significantly distorted and is separated from the
      third helix by an extended turn which is subject to conformational averaging on
      an intermediate time scale. Helix 3 forms a classical amphipathic helix with
      polar and charged residues exposed to the solvent. Upon titration with DNA,
      resonance shifts in the backbone and Asn and Gln side-chain amides indicate that
      helix 3 acts as the recognition helix of the heat shock transcription factor.

PMID- 7634101
TI  - Mutational analysis of the DNA-binding domain of yeast heat shock transcription
      factor.
AB  - Both randomized oligonucleotide cassette mutagenesis and site-directed
      mutagenesis have been used in combination with a yeast genetic screen to identify
      critical residues in the DNA-binding domain of heat shock transcription factor
      from Saccharomyces cerevisiae. Most of the surface residues in this highly
      conserved domain can be changed to alanine with no observable effect on function.
      Of nine critical residues identified in this screen, five are within helix alpha
      3, previously designated as the probable DNA recognition helix in the crystal
      structure of the Kluyveromyces lactis protein. The other four residues may be
      involved in DNA-binding or protein-protein interactions.

PMID- 7634102
TI  - 2.1 A resolution refined structure of a TATA box-binding protein (TBP).
AB  - The three-dimensional structure of a TATA box-binding protein (TBP2) from
      Arabidopsis thaliana has been refined at 2.1 A resolution. TBPs are general
      eukaryotic transcription factors that participate in initiation of RNA synthesis
      by all three eukaryotic RNA polymerases. The carboxy-terminal portion of TBP is a
      unique DNA-binding motif/protein fold, adopting a highly symmetric alpha/beta
      structure that resembles a molecular saddle with two stirrup-like loops. A ten
      stranded, antiparallel beta-sheet provides a concave surface for recognizing
      class II nuclear gene promoters, while the four amphipathic alpha-helices on the
      convex surface are available for interaction with other transcription factors.
      The myriad interactions of TBP2 with components of the transcription machinery
      are discussed.

PMID- 7634103
TI  - 1.9 A resolution refined structure of TBP recognizing the minor groove of
      TATAAAAG.
AB  - The three-dimensional structure of a TATA box-binding protein (TBP) from
      Arabidopsis thaliana complexed with a fourteen base pair oligonucleotide bearing
      the Adenovirus major late promoter TATA element has been refined at 1.9 A
      resolution, giving a final crystallographic R-factor of 19.4%. Binding of the
      monomeric, saddle-shaped alpha/beta protein induces an unprecedented
      conformational change in the DNA. A detailed structural and functional analysis
      of this unusual protein-DNA complex is presented, with particular emphasis on the
      mechanisms of DNA deformation, TATA element recognition, and preinitiation
      complex assembly.

PMID- 7634105
TI  - Naltrexone gains alcoholism indication.

PMID- 7634104
TI  - Frequency of sickle cell crises cut by hydroxyurea use.

PMID- 7634106
TI  - Minnesota pharmaceutical care institute receives $1 million.

PMID- 7634107
TI  - Labor department figures show smaller increases in consumer prices for medical
      care, wholesale prices for prescription drugs.

PMID- 7634108
TI  - Report rates needlestick prevention devices for i.v. therapy.

PMID- 7634109
TI  - Employer health benefit costs drop in 1994.

PMID- 7634110
TI  - HMO enrollment continues fast growth.

PMID- 7634111
TI  - Zeneca agreement marks drug companies' foray into patient care.

PMID- 7634112
TI  - Henry Ford Hospital, Detroit, takes first prize in Abbott competition.

PMID- 7634113
TI  - Choosing sites for ASHP meetings.

PMID- 7634114
TI  - Are Proventil Repetabs and Volmax therapeutically equivalent?

PMID- 7634115
TI  - Intravenous immune globulin for prevention of bacterial infections in pediatric
      AIDS patients.
AB  - The immunologic and clinical abnormalities associated with pediatric human
      immunodeficiency virus (HIV) infection are reviewed, the rationale for using
      intravenous immune globulin (IVIG) to prevent serious bacterial infections is
      described, and clinical experience with IVIG for this indication is summarized.
      Immunologic and clinical abnormalities seen in pediatric HIV-infected patients
      differ from those seen in adult HIV-infected patients. In pediatric patients,
      impaired B-cell activity is an early and prominent manifestation of HIV
      infection. Infants infected with HIV do not develop the antigen-specific B- and T
      cell clones required for immunologic memory, amplification, and production of
      specific antibodies. B-cell defects and lack of memory B cells result in a high
      rate of serious bacterial infections in HIV-infected children compared with
      adults. Natural killer cell dysfunction may also increase HIV-infected children's
      susceptibility to secondary infections. IVIG therapy in HIV-infected pediatric
      patients is based on evidence of impaired antibody function in these patients,
      although this use remains controversial. Case reports and one unblinded
      comparative study published during the 1980s suggest that IVIG may decrease
      morbidity and improve cellular and humoral immune response. One recent large
      scale, double-blind, placebo-controlled study showed that IVIG 400 mg/kg every 28
      days can decrease the morbidity associated with serious bacterial infections in
      HIV-infected children with CD4 cell counts of > 200 cells/cu mm. Another study
      involving HIV-infected children receiving concurrent zidovudine demonstrated that
      IVIG helped prevent serious bacterial infections in children who were not
      concurrently receiving trimethoprim-sulfamethoxazole but not in those who were.
      Although IVIG has not been shown to alter mortality in HIV-infected children,
      regular use may decrease the morbidity associated with serious bacterial
      infections.

PMID- 7634116
TI  - Effect of production environment on labor demand in Veterans Affairs medical
      center pharmacies.
AB  - The relationship between pharmacy production environment and labor-time
      requirements was estimated by using data from Veterans Affairs medical center
      (VAMC) pharmacies. Economic theory was used to derive equations for estimating
      labor-time requirements for pharmacy services that take into account differences
      in production environment (factors that cannot be controlled by the pharmacy
      manager within a given observation period, such as pharmacy service mix and
      distance to patient care wards). The equations were estimated by using
      information obtained from the Department of Veterans Affairs (VA) and from a mail
      survey of VAMC pharmacy chiefs. The resulting estimates of labor-time
      requirements were compared with pharmacy labor-time requirements produced by the
      VA in 1989. Labor-time requirements varied dramatically with production
      environment, and the labor-time requirements calculated in this study generally
      exceeded those used by the VA. Accurate forecasts of required pharmacist and
      technician labor time must take into account the production environment within
      each pharmacy.

PMID- 7634117
TI  - Implementation and evaluation of an automated dispensing system.
AB  - An institution's experience in replacing a traditional unit dose cassette
      exchange system with an automated dispensing system is described. A 24-hour unit
      dose cassette-exchange system was replaced with an automated dispensing system
      (Pyxis's Medstation Rx) on a 36-bed cardiovascular surgery unit and an 8-bed
      cardiovascular intensive care unit. Significantly fewer missing doses were
      reported after Medstation Rx was implemented. No conclusions could be made about
      the impact of the system on the reporting of medication errors. The time savings
      for pharmacy associated with the filling, checking, and delivery of new
      medication orders equated to about 0.5 full-time equivalent (FTE). Medstation Rx
      also saved substantial nursing time for acquisition of controlled substances and
      for controlled-substance inventory taking at shift changes. A financial analysis
      showed that Medstation Rx could save the institution about $1 million over five
      years if all personnel time savings could be translated into FTE reductions. The
      automated system was given high marks by the nurses in a survey; 80% wanted to
      keep the system on their unit. Pilot implementation of an automated dispensing
      system improved the efficiency of drug distribution over that of the traditional
      unit dose cassette-exchange system.

PMID- 7634119
TI  - Invisible care.

PMID- 7634118
TI  - Recommendation of treatment that would allow parole.

PMID- 7634120
TI  - Stability of ticarcillin disodium in polypropylene syringes.

PMID- 7634121
TI  - Fluoroquinolone bioavailability in patients receiving nutritional supplements.

PMID- 7634122
TI  - Use of total nutrient admixtures should not be limited.

PMID- 7634123
TI  - Use of total nutrient admixtures should not be limited.

PMID- 7634124
TI  - Personal and fixed-site ozone measurements with a passive sampler.
AB  - Personal exposures to ozone were measured in the summers of 1992 and 1993 in the
      Fraser Valley, a suburban and rural river valley bordering the metropolitan
      region of Vancouver, British Columbia (population approximately 1.8 million). In
      1992, two groups of 25 healthy individuals were selected for 14 consecutive days
      of 24-hour personal monitoring, based on prior expectations of their activity
      patterns. The first group, composed of adult healthcare workers, was expected to
      spend most of the work day indoors or commuting. The second group, teenage camp
      counselors, was expected to spend more time outdoors. Time-activity data were
      collected to investigate the association between activity patterns and ozone
      exposures. In 1993, 15 adult farmworkers wore personal ozone samplers during
      their workday, which was spent entirely outdoors. Personal monitoring was
      conducted with a nitrite-coated filter passive ozone sampler described by
      Koutrakis and colleagues. Ozone collection rates were determined empirically by
      collocation of the passive samplers with continuous ozone analyzers at fixed
      sampling sites. Sampler performance was assessed by collecting several duplicate
      personal samples. Although ozone levels were low (< 35 ppb 24-hour average)
      during both summer sampling periods, the passive ozone samplers agreed well with
      collocated UV absorption ozone measurements. Based on replicate personal samples,
      we estimated that personal measurements differing by more than 35% were
      associated with true differences in exposure. Within the two groups with varying
      time activities, differences in ozone exposures were associated with the fraction
      of time spent outdoors. Similarly, differences in ozone exposures were observed
      between the three sampling populations, with higher exposures recorded in the
      group that spent more time outdoors.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7634125
TI  - The sensitivity of probabilistic risk assessment results to alternative model
      structures: a case study of municipal waste incineration.
AB  - In this analysis, human health risk due to exposure to municipal waste
      incinerator emissions is assessed as an example of the application of
      probabilistic techniques (e.g., Monte Carlo or Latin Hypercube simulations).
      Incinerator risk assessments are characterized by the dominance of indirect
      exposure, thus this analysis focuses on exposure via the ingestion of locally
      grown foods. In addition, since exposure to 2,3,7,8-TCDD drives most incinerator
      risk assessments, this compound is the subject of the illustrative calculations.
      An important part of probabilistic risk assessment is determining the relative
      influence of the input parameters on the magnitude of the variance in the output
      distribution. This constitutes an important step toward prioritizing data needs
      for additional research. However, under various possible model forms reflecting
      incompletely understood aspects of contaminant transport, differences may be
      observed in estimates of risk, variance in risk, and the relative contributions
      of individual uncertain and variable inputs to the variance. In this analysis, a
      sequential structural decomposition of the relationships between the input
      variables is used to partition the variance in the output (i.e., risk) to
      identify the most influential contributors to overall variance among them. For
      comparison, the partitioning of variance is repeated, using techniques of
      multivariate regression. In summary, this study considers the degree to which
      results of a probabilistic assessment are contingent on critical model
      assumptions about the representation of deposition velocity. Specifically, this
      analysis assesses the impact on the results of uncertainty about the best model
      of the vapor/particle partitioning behavior of semi-volatile airborne pollutants.

PMID- 7634126
TI  - Determination of VOC emission rates and compositions for offset printing.
AB  - The release rates of volatile organic compounds (VOC) as fugitive emissions from
      offset printing are difficult to quantify, and the compositions are usually not
      known. Tests were conducted at three offset printing shops that varied in size
      and by process. In each case, the building shell served as the test "enclosure,"
      and air flow and concentration measurements were made at each air entry and exit
      point. Emission rates and VOC composition were determined during production for
      (1) a small shop containing three sheetfed presses and two spirit duplicators
      (36,700 sheets, 47,240 envelopes and letterheads), (2) a medium-size industrial
      in-house shop with two webfed and three sheetfed presses, and one spirit
      duplicator (315,130 total sheets), and (3) one print room of a large commercial
      concern containing three webfed, heatset operations (1.16 x 10(6) ft) served by
      catalytic air pollution control devices. Each test consisted of 12 one-hour
      periods over two days. Air samples were collected simultaneously during each
      period at 7-14 specified locations within each space. The samples were analyzed
      by gas chromatography (GC) for total VOC and for 13-19 individual organics.
      Samples of solvents used at each shop were also analyzed by GC. Average VOC
      emission rates were 4.7-6.1 kg/day for the small sheetfed printing shop, 0.4-0.9
      kg/day for the industrial shop, and 79-82 kg/day for the commercial print room.
      Emission compositions were similar and included benzene, toluene, xylenes,
      ethylbenzene, and hexane. Comparison of the emission rates with mass balance
      estimates based on solvent usage and composition were quite consistent.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7634127
TI  - Effect of masticatory muscle fatigue on cranio-vertical head posture and rest
      position of the mandible.
AB  - The aim of this study was to investigate whether induced fatigue of the
      masticatory muscles had any influence on the head posture, and whether this
      influence is related to the rest position and the movement characteristics of the
      mandible. The sample consisted of 13 female individuals, aged 23-34 yr. For the
      evaluation of possible changes in the natural cranio-vertical head posture,
      standardized facial profile photographs were used. Photographs were also used for
      the study of the facial characteristics. The freeway space and the opening and
      closing velocity of the mandibular displacement, as well as the duration of the
      masticatory cycles, were monitored with an optoelectronic method. A controlled
      dynamic fatigue was induced by a specially constructed spring-loaded device
      placed in the premolar region. No significant changes in the mean cranio-vertical
      postural position of the head were found during the various recording stages,
      while the freeway space was found to increase significantly after the fatigue
      test. No significant differences were observed concerning the average values of
      the mandibular movement characteristics. The analysis of the association between
      the individual changes showed an increase in the freeway space after the fatigue
      test in the subjects which exhibited an increase in the duration of the
      masticatory cycle in that period. No significant associations could be found
      between the changes in the head posture and the mandibular movement
      characteristics. Also, no significant correlation could be found between the
      facial type of the subjects and the variables studied.

PMID- 7634128
TI  - Localization of S-adenosylmethionine decarboxylase in murine tissues by
      immunohistochemistry.
AB  - S-adenosylmethionine decarboxylase (AdoMetDC), one of three key enzymes in
      polyamine biosynthesis, is present in minute concentrations in adult tissues,
      whereas increased AdoMetDC activity occurs in conjunction with differentiation
      and growth. The occurrence of AdoMetDC in tissues has earlier been studied by
      biochemical technique only. In this work, an antiserum against recombinant human
      AdoMetDC was used to investigate the localization of the enzyme in different
      mouse tissues. In all tissues studied, immunolabeling was seen in cytoplasm,
      while cell nuclei were negative. In the kidney, AdoMetDC immunoreactivity was
      confined to the inner part of the cortex; the outer part of the cortex and the
      medulla displayed only a weak AdoMetDC immunoreaction. In the cortex, renal
      tubules were strongly reactive, while renal corpuscules were weakly
      immunolabeled. In developing teeth, AdoMetDC immunoreactivity displayed a
      gradient of distribution, the immunolabeling intensity being increased from the
      cervical region to the tip of the cusps. In the incisor, post-secretory
      ameloblasts were strongly labeled. In the oral mucosa, epithelial cells
      demonstrated stronger immunolabeling than did cells of the subjacent connective
      tissue. As for muscle cells, immunoreactive material was confined to the
      periphery of the fibers. In vitro, treatment with DL-alpha
      difluoromethylornithine (DFMO) or methylglyoxal bis-(guanylhydrazone) (MGBG) led
      to an increase in AdoMetDC. It can be concluded that antibodies to recombinant
      human AdoMetDC provide a tool for the immunohistochemical localization of
      AdoMetDC, and that the distribution of the enzyme in the tissues studied gives
      further support to the importance of polyamines in the development and functions
      of these organs.

PMID- 7634129
TI  - Characterization of interstitial collagenases in jaw cyst wall.
AB  - Neutral salt extracts of 14 specimens of jaw cysts were prepared.
      Histopathological analysis showed that the specimens consisted of 6 radicular
      cysts, 6 dentigerous cysts, 1 residual cyst, and 1 odontogenic keratocyst. One
      periapical granuloma, 1 dental follicle and a sample of clinically healthy oral
      mucosa were similarly processed and used as controls. Measurement of collagenase
      activity by monitoring the formation of specific degradation products of type I
      and II collagen in solution by SDS-PAGE demonstrated that all the cyst extracts
      contained collagenase, some of which was endogenously activated. Cyst wall
      collagenase preferably degraded type I over type II collagen, which suggests that
      the degradation was due to MMP-1 (matrix metalloproteinase-1) rather than the MMP
      8 type. This was further supported by the doxycycline-inhibition profile of cyst
      collagenase, which was similar to that of MMP-1. Part of the cyst wall
      collagenase was in latent proenzyme form and probably derived, at least in part,
      from the newly synthesized intracellular collagenase pool. Latent cyst
      collagenase was efficiently activated with phenylmercuric chloride and to a
      lesser extent by gold (I) thioglucose and NaOCl. Western-blotting, using specific
      antibodies against collagenase from human polymorphonuclear neutrophilic
      leukocytes (MMP-8) and from fibroblasts (MMP-1), revealed a typical 55/45 kDa
      doublet; also MMP-8 in the latent 80 kDa form and fragmented to 65 kDa active
      species were found. These results suggest the presence of MMP-1 and, to a lesser
      extent, MMP-8 type collagenase in the cyst wall.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7634130
TI  - pH effects on experimental wound healing of human fibroblasts in vitro.
AB  - The aim of the present study was to examine to what extent pH affects human
      fibroblast repopulation of an experimental wound in vitro laying special emphasis
      on cell migration, DNA synthesis, and alterations in cell morphology. Wounds were
      simulated in vitro by partially scraping off monolayers of human embryonic
      diploid lung fibroblast and human periodontal ligament fibroblast-like cells
      respectively. The wounded monolayers were cultured at pHs ranging from 7.2 to
      8.4. The experiments were evaluated by autoradiography as well as light and
      scanning electron microscopic techniques. A significant, approximately linear,
      decrease was noted both in cell migration into and DNA synthesis in the
      experimental wounds as a result of pH increase. The surviving cells in the wounds
      showed cytoplasmatic vacuoles and blebbing at pH levels above 7.8. Clinical
      implications of these results for endodontic calcium hydroxide treatment are that
      hydroxyl ions, diffusing through root dentin, may interfere with vital cell
      functions necessary for healing on the root surface.

PMID- 7634131
TI  - Effect of doxycycline on surgically induced osteoclast recruitment in the rat.
AB  - The influence of systemic doxycycline on the number of surgically induced
      osteoclasts was studied in young albino rats. Forty Wistar rats, aged 50 d at the
      start of the experiments, were randomly assigned to two groups. The experimental
      group (20 animals) received 0.5 mg/ml doxycycline added to the drinking water.
      Mucoperiosteal flaps were raised on the palatal aspect of left maxillary molars
      in all animals. Two rats from each group were killed daily during a post
      operative period of 10 d, and specimens were prepared for light microscopy.
      Cellular counts in serial sections of crestal bone indicated a delay of initial
      surface colonization of 2 d. Statistical analysis revealed a smaller number of
      osteoclasts in doxycycline-treated animals as compared to control rats. In
      conclusion, systemic doxycycline suppresses recruitment of osteoclasts following
      surgery.

PMID- 7634132
TI  - Effect of sucrose and xylitol diets on dentin formation and caries in rat molars.
AB  - To investigate the effects of a high sucrose diet and xylitol on secondary
      dentinogenesis and dentinal caries, a part of the sucrose in a high-cariogenic
      diet was replaced by xylitol. Fifty-four 3-wk-old Wistar rats were labeled with
      tetracycline and divided into groups. One group received a high sucrose diet (43%
      sucrose). In two other groups 5% and 20% of the sucrose was replaced by xylitol.
      A control group received non-cariogenic food. Six weeks later the mandibles were
      sectioned sagittally. Schiff staining was used to classify the caries, and the
      areas of dentin formed during the experiment and dentinal caries in first and
      second molars were measured planimetrically. The high sucrose diet reduced dentin
      formation of the molars, and this reduction was further increased by xylitol.
      Caries initiation and dentinal caries progression were significantly reduced by
      20% xylitol, whereas only a slight reduction in caries progression was observed
      with 5% xylitol. Also, a negative correlation between the dentin formation and
      dentinal caries progression was observed in the high sucrose and 5% xylitol
      groups. In conclusion, xylitol together with high sucrose reduced dentin
      formation and dentinal caries progression, and the effect was dose-dependent.

PMID- 7634133
TI  - Development of plaque and gingivitis after mouthrinsing with 0.2% delmopinol
      hydrochloride.
AB  - A double-blind, randomized, 2-wk experimental gingivitis clinical trial with
      cross-over design in 14 dental students was conducted in order to study the
      efficacy and safety of delmopinol hydrochloride solution (2 mg/ml), used with no
      other oral hygiene procedures, in comparison with placebo. Plaque formation was
      measured by the Quigley & Hein Plaque Index and gingivitis was assessed by
      bleeding on probing according to Muhlemann & Son. Rinsing with delmopinol
      resulted in lower plaque scores compared to placebo. The development of
      gingivitis was weak during the 2-wk test periods, and thus no conclusive results
      were obtained. As in previous studies, the most frequent adverse event when
      rinsing with delmopinol was a transient anaesthetic sensation in the oral mucosa.
      The results showed that rinsing with delmopinol hydrochloride solution (2 mg/ml)
      for 60 s twice daily with no other oral hygiene procedures led to less plaque
      formation than rinsing with placebo. This study also showed good tolerance and
      acceptability of mouthrinsing with delmopinol.

PMID- 7634134
TI  - Experiments with two-phase plaque-inhibiting mouthrinses.
AB  - Reports indicate that oil/water mouthrinses with an aqueous phase containing an
      antibacterial agent, reduce the amount of volatile bacterial products in
      expiration air compared with aqueous mouthrinses. These systems have not,
      however, been tested concerning antiplaque activity. The aim of the present study
      was to examine the plaque-inhibiting effect of a mouthrinse with an aqueous phase
      containing 0.2% chlorhexidine (CHX) and an oily phase (soya oil) containing 0.3%
      triclosan. A test panel rinsed with the mouthrinses twice daily for 4 d. The
      mouthrinse containing CHX and triclosan in two phases was significantly better
      than the negative control (water). However, it was not as effective as the rinse
      consisting of an aqueous phase with chlorhexidine combined with an oily phase
      without triclosan. A two-phase mouthrinse with soya oil containing 0.3% triclosan
      was not superior to soya oil alone, and the combination of CHX and triclosan in a
      two-phase rinse was not as effective as 0.1% CHX alone in water. No beneficial
      effect on plaque inhibition could thus be found by using a two-phase system with
      two different antibacterial agents (one water soluble and one lipid soluble).
      Soya oil without triclosan rendered higher plaque inhibition than the control,
      presumably due to formation of a hydrophobic layer on the tooth surfaces.

PMID- 7634136
TI  - Ceramic inlay movement during polymerization of resin luting cements.
AB  - In cavities with no support for inlays, polymerization contraction of the resin
      cement may move the ceramic inlay axially. The purpose of this study was to
      determine the velocity and extent of such movement. Cylindrical ceramic inlays
      were placed in dentin cavities filled with one of four commercially available
      resin composite cements. An initial standardized 200-microns-thick cement film
      was created. The movement of the ceramic inlay during polymerization of one of
      the resin cements was measured by a dial gauge. The velocity of the inlay
      movement decreased exponentially with time and with a velocity constant of 0.09
      min-1. The majority of the movement occurred within the first 12 min after
      photopolymerization and probably continued for several days, reaching an
      estimated value of 5.8 microns. After 1-2 d of water storage, 1-2-microns
      contraction gaps at the cavity floors were observed microscopically for every
      cement used. It is concluded that in cavities without support for the inlay,
      about 2/3 of the resin cement contraction results in movement of the inlay and
      about 1/3 results in formation of gaps at the cavity floors.

PMID- 7634135
TI  - Inhibitory effect on S. mutans by fluoride-treated conventional and resin
      reinforced glass ionomer cements.
AB  - The aim of the present study was to study the effect of fluoride gel treatment on
      fluoride release and inhibition of acid production of Streptococcus mutans by
      different glass ionomer cements. Test slabs of four glass ionomer materials were
      fitted into the bottom of a test tube. A layer of S. mutans cells was centrifuged
      onto the test slabs, and the specimens were incubated for 4 h in 1.7% sucrose
      solution. Incubations were made using fresh, aged (29 d), aged and F-treated
      (1.25% F-gel), and aged, F-treated and aged samples (n = 15 per group). After
      each incubation, pH and F contents of the fluid phase were determined. The
      freshly mixed glass ionomer samples released large amounts of fluoride, and the
      pH fall in the fluid phase was significantly inhibited. For aged samples, the
      fluoride release decreased strongly and no inhibitory effect on acid production
      by S. mutans was seen. After application of fluoride gel, fluoride release and
      inhibitory effect were significantly higher than initially for all glass ionomer
      cements. In conclusion, all glass ionomer cements were able to take up fluoride
      and subsequently release it, which resulted in reestablishment of their
      antibacterial effect. The patterns of fluoride release and antibacterial action
      were virtually the same for conventional and resin-reinforced glass ionomer
      cements.

PMID- 7634137
TI  - Intermediate filament proteins.

PMID- 7634138
TI  - Refractive index of the human corneal epithelium and stroma.
AB  - BACKGROUND: The refractive index of the cornea must be determined to optically
      perfect keratorefractive procedures. There are very few empirical measurements of
      the human corneal refractive index described in the literature. Throughout its
      depth, the cornea demonstrates regional variations in physiological properties
      such as swelling/de-swelling characteristics. These properties suggest there may
      be a difference in the refractive index between the anterior and posterior
      corneal surfaces. METHODS: The refractive index of the human corneal epithelium
      of 10 eyes was measured, in vivo, using a modified hand-held refractometer. The
      refractive indices of the anterior and posterior surfaces of the bare stroma of
      fresh human corneas were measured using a bench model Abbe refractometer.
      RESULTS: The mean refractive index of the epithelium, stromal anterior and
      posterior surfaces were 1.401 (SD +/- 0.005), 1.380 (SD +/- 0.005), and 1.373 (SD
      +/- 0.001) respectively. CONCLUSIONS: The refractive index of the cornea is not
      uniform. The calculated dioptric power of the corneal epithelium is approximately
      -1.40 diopters (D). The varying refractive index does not significantly affect
      the total dioptric power of the cornea. The varying refractive index of the
      cornea has the potential to significantly contribute to the overall optical
      performance of the eye in relation to refractive surgery. The results should be
      incorporated into mathematical models, comparing and contrasting the optical
      performance of the eye before and after surgery.

PMID- 7634139
TI  - Tear fluid cellular fibronectin levels after photorefractive keratectomy.
AB  - BACKGROUND: Fibronectin is supposed to have an important role in wound healing.
      The extradomain A-containing cellular fibronectin (EDAcFn) refers to fibronectin,
      which instead of being a hepatocyte derived component of blood plasma or body
      fluids, is produced locally. The present study was undertaken to clarify the
      possible changes in excretion of EDAcFn in tears following excimer laser
      photorefractive keratectomy (PRK). METHODS: An immunoassay was used to determine
      EDAcFn concentrations in human tear fluid samples of 11 eyes after PRK. Tear
      fluids were collected with scaled microcapillaries preoperatively as well as 1,
      2, and 7 days after PRK. The time used to collect a known volume of tears was
      registered. This was done to estimate the dilution effect related to the
      hypersecretion of tears after PRK. RESULTS: The mean preoperative tear fluid
      EDAcFn concentration was 0.28 +/- 0.07 ng/microliter with a wide range (0.05 to
      0.63). The tear fluid flow-corrected excretion of EDAcFn was 1.36 +/- 0.35 ng/min
      (range, 0.145 to 3.50). There was a significant increase in both postoperative
      tear fluid flow and excretion of EDAcFn on days 1 and 2. The elevation of the
      mean EDAcFn concentration did not decrease in spite of reflex tearing. The mean
      excretion of EDAcFn in tears was 28-fold on the first and 17-fold on the second
      postoperative day. Normal level was reached by day 7. CONCLUSION: There is a
      rapid increase in excretion of EDAcFn in tears following PRK. This seems to last
      only as long as an epithelial defect persists. The epithelium of all eyes healed
      in 3 to 4 days in spite of wide interindividual variations in both tear fluid
      flow and EDAcFn excretion.

PMID- 7634140
TI  - Epithelial alterations following photorefractive keratectomy for myopia.
AB  - BACKGROUND: A retrospective observational study was conducted to test the
      hypothesis that there is clinically measurable epithelial hyperplasia after
      photorefractive keratectomy (PRK), and to determine its effect on the epithelial
      oxygen uptake rate. METHODS: One hundred myopic eyes who had been previously
      treated unilaterally with PRK were examined. Fifty eyes were treated with the
      Summit excimer laser (Summit Technology, Waltham, Mass) 27 +/- 7 months
      previously with ablation zone diameters of 4.1, 4.3, 4.5, or 5.0 mm. Fifty eyes
      were treated with the VISX excimer laser (VISX Inc, Sunnyvale, Calif) 5 +/- 4
      months previously with one ablation zone diameter of 6.0 mm. The untreated eyes
      served as controls. Epithelial thickness was measured at a standardized central
      area within the ablation zone with a modified optical pachometer. Oxygen uptake
      rate was measured in a subgroup of 30 eyes (20 Summit and 10 VISX). RESULTS: The
      epithelium after PRK was 24% thicker than in the control eye in the Summit group
      (mean difference 13 +/- 10 microns; p < .01) and 7% thinner in the VISX group
      (mean difference -4 +/- 10 microns; p < .01). A higher oxygen uptake rate
      correlated with a thicker epithelium (r = 0.42; p < .05). CONCLUSIONS: The
      epithelium was significantly thicker after PRK between 13 and 37 months after
      treatment with the Summit excimer laser using ablation zone diameters of 4.1 to
      5.0 mm. The epithelium was thinner between 1 and 15 months after treatment with
      the VISX laser using an ablation zone diameter of 6.0 mm. An increase in oxygen
      uptake rate reflected the metabolic rate of a greater number of cells in the
      hyperplastic layer.

PMID- 7634141
TI  - Repeatability of corneal topography: the "corneal field".
AB  - BACKGROUND: The purpose of this study was to determine the interoccasion
      repeatability of keratometry, photokeratography, and videokeratography and to
      describe the "corneal field," a scheme for explaining videokeratography results.
      METHODS: A single examiner obtained corneal curvature measurements with a
      keratometer, a photokeratoscope, and the TMS-1 in 29 adult patients on two
      occasions. RESULTS: Estimates for the repeatability of keratometry were +/- 0.49
      and +/- 0.65 diopters (D) for the horizontal and vertical meridians respectively.
      The repeatability of photokeratography was +/- 0.90 and +/- 1.21 D. We presented
      a rational method for presenting numeric videokeratographic data by temporally
      and spatially averaging corneal curvature values and grouping them into 24
      regions. The repeatability of videokeratography with the TMS-1 was +/- 0.50 D
      centrally, +/- 0.65 D paracentrally, and +/- 0.80 to +/- 1.00 D in the
      midperiphery. CONCLUSIONS: Repeatability of the photokeratoscope for central
      measurements is considerably worse than the keratometer. The repeatability of
      videokeratography is worse toward the periphery. Refractive surgeons and contact
      lens investigators need to be aware of these limitations so that true change can
      be distinguished from measurement error.

PMID- 7634142
TI  - Release of calcitonin gene-related peptide in tears after excimer laser
      photorefractive keratectomy.
AB  - BACKGROUND: Sensory nerves known to affect corneal healing are damaged to a
      variable degree after photorefractive keratectomy (PRK). To search for nerve
      bound factors involved in corneal healing, we monitored tear fluid calcitonin
      gene-related peptide (CGRP) levels of six human eyes undergoing PRK. METHODS:
      CGRP concentrations were determined using an immunoassay. RESULTS: Normal human
      tear fluid contains CGRP. The mean CGRP concentration was slightly increased
      postoperatively, despite a marked tear fluid hypersecretion. Consequently, an
      almost ten-fold increase in release of CGRP in tears was observed on days 1 and 2
      after PRK. Values measured on day 7 had returned to a normal level. CONCLUSION:
      The observed postoperative increase in release of CGRP in tears may have an
      impact on the healing of PRK wounds. Extensive neural damage following deep
      photoablations may impair healing and should probably be avoided.

PMID- 7634143
TI  - Thermal collateral damage in porcine corneas after photoablation with free
      electron laser.
AB  - BACKGROUND: The study describes a quantitative and systematic investigation of
      the collateral thermal damage during infrared photoablation as a function of
      wavelength between 2.7 and 6.7 microns. METHODS: Using the tunable Free Electron
      Laser at Vanderbilt University, Nashville, Tenn, 60 freshly removed porcine
      cadaver eyes were irradiated at wavelengths between 2.7 and 6.7 microns, at a
      fluence of 1.3 J/cm2. For wavelengths where no photoablation occurred, fluence
      was increased to 3.5 J/cm2; pulse length (macropulse) was 4 microseconds,
      consisting of a train of micropulses (pulse duration 2 ps at a 2.9 GHz repetition
      rate). The corneal buttons were removed and stained with hematoxylin and eosin
      (H&E) and analyzed by histologic micrometry. RESULTS: Two thermal damage zones in
      the remaining tissue were observed: zone 1 showed superficial carbonization and
      measured between 2 and 4 microns; beyond, the eosinophilic zone 2 measured
      between 10 and 100 microns. The extent of zone 2 was inversely related to the
      absorption spectra of the cornea; it was minimal at the 3- and 6-micrometer water
      absorption bands and maximal at minimal target absorption. CONCLUSION: The
      results correlated well with a model of the ablation process. The study provides
      a systematic and predictive element for the determination of collateral thermal
      adverse effects; it does not yet include pulse length variation as a determining
      factor.

PMID- 7634144
TI  - Refractive surgery centers proliferate globally.

PMID- 7634145
TI  - LASIK--the future is now.

PMID- 7634147
TI  - Comparison of polycarbonate and steel test surfaces for videokeratography.
AB  - BACKGROUND: Assessing video imaging systems for measuring corneal topography
      often requires test surfaces. Steel bearings have been employed, but
      manufacturers caution that high reflectance (> 90%) relative to the eye (< 10%)
      may compromise test findings. The differences between steel and polycarbonate
      test surfaces are quantified in this study. METHODS: Images of a steel and a
      polycarbonate sphere of known radius of curvature were obtained with the
      Tomey/Computed Anatomy Topographic Modeling System (TMS, Cambridge, Mass).
      Analysis was performed on the raw video data files and the resultant surface
      curvature estimates. RESULTS: The raw video images differed sufficiently to
      affect image processing. Polycarbonate yielded consistently better images. Many
      steel images (approximately 25%) contained data points that could not be
      processed; calculated surface contour was more variable for these. Differences
      were less obvious when these images were removed from the pool. CONCLUSIONS:
      Results support the manufacturer's caution against the use of steel surfaces for
      testing or calibration of the TMS instrument. Problems appear due to the
      fundamental differences in the intensity distributions of video images captured
      from high- and low-reflectance surfaces.

PMID- 7634146
TI  - Forward light scatter at one month after photorefractive keratectomy.
AB  - BACKGROUND: Although it is known that backward light scatter increases
      transiently following most excimer laser photorefractive keratectomies (PRKs), it
      is not clear that there is a significant increase in forward light scatter, which
      is of primary concern for the patient. The object of this study was to determine
      if there is a significant change of forward light scatter at 1 month after (PRK)
      with an ablation zone diameter of 6 mm. METHODS: Overlapping subsets of 24 normal
      myopic eyes were tested before (on the day of surgery) and 1 month after PRK,
      using three instruments: a Stray Light Meter (16 eyes); a Computerized Stray
      Light Meter (14 eyes); and a mesopic Increment Threshold-Glare Paradigm (six
      eyes). Differences between the two eyes before PRK were compared with the
      differences between the same eye before and after PRK, using repeated measured
      analysis of variance. In addition, increment threshold data obtained from 22 eyes
      after PRK were compared with those of 60 controls of the same age range and
      distribution by a t test. RESULTS: None of the statistical comparisons approached
      significance at the alpha = 0.05 level. Changes in light scatter as small as a
      factor of 1.95 (Stray Light Meter) and 1.55 (Increment Threshold-Glare Paradigm)
      could be detected as significant with a high power (0.8). Changes larger than a
      factor of 21 could be detected with a power of 0.8 for the Computerized Stray
      Light Meter. CONCLUSIONS: In these data, there is no support for the hypothesis
      that forward light scatter increases significantly 1 month after PRK with an
      ablation zone of 6 mm. Any increases in forward light scatter are unlikely to be
      greater than a factor of 1.5 to 2 under daytime or nighttime illumination
      conditions.

PMID- 7634148
TI  - Corneal topographic changes induced by pterygia.
AB  - BACKGROUND: This study characterizes the topographic changes induced by pterygia.
      METHODS: Using data obtained from a videokeratoscope (TMS-1), we assessed the
      topographic changes of corneas from 24 consecutive eyes with pterygia. RESULTS:
      Each pterygium induced a localized area of flattening central to its apex of
      38.00 +/- 2.80 diopter (D) which was significantly flatter (p < .0001) than the
      mean corneal power (43.70 +/- 1.70), minimum corneal power (MinK, 42.70 +/-
      2.10), and the power of the flattest corneal meridian (42.90 +/- 1.90).
      CONCLUSIONS: Our topographic findings characterize an area of localized corneal
      flattening central to the apex of pterygia. It is not known if this pterygium
      associated corneal flattening influences the centripetal growth of pterygia or
      their tendency not to cross the visual axis.

PMID- 7634149
TI  - Corneal perforation in a premature infant.
AB  - BACKGROUND: Few cases of corneal perforation in a premature infant have been
      described in the literature. METHODS: Identical twins were born at 30-weeks
      gestation. One twin developed a corneal epithelial defect, infiltration, and
      perforation with extrusion of intraocular contents, requiring an emergency
      penetrating keratoplasty. The second twin developed a progressive corneal
      opacity, requiring a lamellar keratectomy. RESULTS: After penetrating
      keratoplasty, the patient developed absolute glaucoma with buphthalmos, leading
      to enucleation. The twin's lamellar keratectomy specimen proved to be a dermoid.
      CONCLUSIONS: One must be aware of the danger of the development of spontaneous
      corneal perforation with extrusion of intraocular contents in premature infants
      presenting at birth with an epithelial defect.

PMID- 7634151
TI  - Proliferation of pituitary corticotrophs following adrenalectomy as revealed by
      immunohistochemistry combined with bromodeoxyuridine-labeling.
AB  - Proliferation of corticotrophs following adrenalectomy (ADX) was studied by a
      combination of bromodeoxyuridine (BrdU)-labeling and immunohistochemistry. Rats
      were adrenalectomized, allowed to survive for 1, 3, 7, and 14 days and given 100
      mg/kg body wt BrdU 3 h before sacrifice. BrdU and adrenocorticotropic hormone
      (ACTH) were detected in the same sections of the anterior pituitary using double
      labeling immunohistochemistry. BrdU-labeled cells in the pituitary showed a
      tendency to increase until 1 week after ADX and slightly decreased at 2 weeks.
      Corticotrophs were increased to about 1.5 times of the control level 1-2 weeks
      after ADX. The number of cells double-labeled with both BrdU and ACTH increased
      markedly after ADX, suggesting active mitosis of existing corticotrophs. On the
      other hand, the ratios of these double-stained cells to all BrdU-labeled cells
      and to all corticotrophs were 5-7% and 0.9-1.3%, respectively, even after ADX,
      suggesting that the majority of corticotrophs which were increased after ADX were
      recruited from some other type of immature cells. The extent to which the two
      mechanisms are involved in hyperplasia of corticotrophs after ADX remains to be
      elucidated.

PMID- 7634150
TI  - Immunocytochemical localization of elastase 1 in human pancreas.
AB  - By light and electron microscopic immunocytochemistry the distribution is
      described of human pancreatic elastase 1 (E1) during ontogenesis, in adults, in
      cases of acute and chronic pancreatitis, acute pancreatic ischaemia as well as
      pancreatic tumours. E1-positive cells were first detected in ductal sprouts in
      the 14th gestational week. Complete acini expressing E1 could be found from the
      17th to the 20th week of gestation onwards. Scattered distinct E1-positive
      epithelia could be found in the ducts of fetal and adult pancreas. By
      immunoelectron microscopy, E1 was localized in rough endoplasmic reticulum,
      condensing vacuoles, zymogen granules of acinar epithelia and in acinar lumina.
      E1 appeared to be distributed homogeneously in zymogen granules. As specific
      markers of acinar cells, both monoclonal antibodies under study identified
      heterotopic pancreatic acini in peribiliar glands of the liver and also helped to
      visualize different damage patterns in pancreatitis. The acinar epithelia
      surrounding acute lipolytic necroses initially reacted more intensely with the E1
      antibodies than undamaged pancreatic tissue. In acute ischaemia, acinar cells
      which are dissociated from intercalated ducts lost their immunocytochemical
      reactivity for E1. Pancreatic parenchyma involved in advanced acute pancreatitis
      as well as in chronic inflammation was detected only weakly by both E1
      antibodies. However, atrophic lobules in post-inflammatory scars were stained
      more intensely by the E1-antibodies than normal parenchyma. Pancreatic tumours
      (adenomas, adenocarcinomas, solid-cystic tumours and islet cell tumours) were not
      labelled by these antibodies.

PMID- 7634152
TI  - Enterocytes in the follicle-associated epithelia of rabbit small intestine
      display distinctive lectin-binding properties.
AB  - Glycoconjugate expression in follicle-associated epithelia has been examined by
      application of a panel of lectins to fixed preparations of rabbit small
      intestine, including Peyer's patches. Each of the lectins examined (wheat germ
      agglutinin, peanut agglutinin, Ulex europaeus agglutinin I and Bandeiraea
      simplicifolia agglutinin II) exhibited a lower affinity for the apical surface of
      the specialised M cells than to columnar enterocytes within the Peyer's patch
      follicle-associated epithelium. Peanut agglutinin differed from the other lectins
      examined in that it displayed a markedly higher affinity for enterocytes within
      the follicle-associated epithelium than the neighbouring villi. This observation
      reveals that the specialised development of the follicle-associated epithelium
      involves expression of distinctive surface properties within the enterocyte
      population in addition to the more widely documented heterogeneous development of
      enterocytes and the specialised M cells.

PMID- 7634153
TI  - Modifications of S100-protein immunoreactivity in rat brain induced by tissue
      preparation.
AB  - Immunocytochemistry using antibodies against various molecular forms of the Ca++
      and Zn(++)-binding S100 proteins predominantly labelled astrocytes. However,
      especially in the neocortex the staining pattern is variable. Methods of tissue
      preparation have been evaluated with the aim to preserve as much S100
      immunoreactivity as possible. Optimal results were obtained after perfusion
      fixation with 4-5% aldehydes, 0.1 M sodium cacodylate, 0.1% CaCl2, pH 7.3. In
      such preparations, astrocytes were completely labelled including their lamellar
      compartments in large parts of the central nervous system. Ca(++)-withdrawal had
      adverse affects on S100 immunoreactivity. Cryostat sections treated with EDTA
      containing solutions before fixation showed that Ca(++)-free S100 can apparently
      not be fixed to the tissue. Perfusion fixatives containing EDTA resulted in
      inhomogeneous loss of S100 staining, indicating a differential susceptibility of
      astrocytic subpopulations. A different type of reduction in S100 immunoreactivity
      occurred around large neocortical blood vessels. Perivascular defects in
      immunostaining occasionally appeared even after optimal fixation, but could be
      regularly provoked by mildly acidic fixation (pH 6.6) or prolonged barbiturate
      anaesthesia. These defects might be based on S100 release into the cerebrospinal
      fluid. Presumably under none of the conditions studied can the immunoreactivity
      of all S100-forms and -fractions be completely preserved in the tissue. However,
      recommendations are presented for optimizing tissue preparation, to the extent
      that premortal modifications affecting the stainability of astrocytes may be
      detected by S100 immunohistochemistry in fixed brain tissue.

PMID- 7634154
TI  - Histochemical localization of heart-type fatty-acid binding protein in human and
      murine tissues.
AB  - Cellular fatty acid-binding proteins (FABP) are a highly conserved family of
      proteins consisting of several subtypes, among them the mammary-derived growth
      inhibitor (MDGI) which is quite homologous to or even identical with the heart
      type FABP (H-FABP). The FABPs and MDGI have been suggested to be involved in
      intracellular fatty acid metabolism and trafficking. Recently, evidence for
      growth and differentiation regulating properties of MDGI and H-FABP was provided.
      Using four affinity-purified polyclonal antibodies against bovine and human
      antigen preparations, the cellular localization of MDGI/H-FABP in human and mouse
      tissues and organs was studied. The antibodies were weakly cross-reactive with
      adipose tissue extracts known to lack H-FABP, but failed to react by Western blot
      analysis with liver-type FABP (L-FABP) and intestinal-type FABP (I-FABP). MDGI/H
      FABP protein was mainly detected in myocardium, skeletal and smooth muscle
      fibres, lipid and/or steroid synthesising cells (adrenals, Leydig cells,
      sebaceous glands, lactating mammary gland) and terminally differentiated
      epithelia of the respiratory, intestinal and urogenital tracts. The results
      provide evidence that expression of H-FABP is associated with an irreversibly
      postmitotic and terminally differentiated status of cells. Since all the antisera
      employed showed spatially identical and qualitatively equal immunostaining, it is
      suggested that human, bovine and mouse MDGI/H-FABP proteins share highly
      homologous epitopes.

PMID- 7634155
TI  - Microwave irradiation of paraffin-embedded tissue sensitizes the TUNEL method for
      in situ detection of apoptotic cells.
AB  - Apoptosis is a morphologically distinct form of programmed cell death that plays
      an important role in the growth regulation of a variety of tissues and also in
      the elimination of self-reacting immunocompetent cells. Several techniques for
      the qualitative and quantitative detection of this process have been established;
      recently, an in situ nick end-labelling technique based on the detection of DNA
      fragmentation, which is a molecular characteristic of apoptotic cell death, was
      described. Applying this method to paraffin sections of human tissues,
      sensitivity was observed to be inconsistently low with regard to the expected
      number of apoptotic cells. In the present study we show that irradiation of the
      tissue sections in 10 mM citrate buffer, pH 6.0, by microwaves at 750 W
      considerably enhances the sensitivity of this nick end-labelling technique.

PMID- 7634159
TI  - Update on four unusual equine dermatoses.
AB  - This article discusses some new thoughts on the pathogenesis of four unusual
      equine dermatoses: reticulated leukotrichia, hyper-esthetic leukotrichia, mane
      and tail dystrophy, and linear alopecia of the Quarter Horse. Although many of
      the thoughts contained herein are speculative, it is hoped that they stimulate
      discussion among those of us interested in the wonderful world of equine
      dermatology. More importantly, it is hoped that they stimulate further
      investigation and research. These diseases represent only the tip of the iceberg
      pf what we don't know about equine skin diseases!

PMID- 7634158
TI  - Overview of equine pruritus.
AB  - Pruritus is a common complaint associated with equine dermatoses. Self-mutilation
      results in alopecia, excoriations, scaling, and crusting; the aesthetic
      appearance of the horse is often ruined and the horse may be unfit for riding or
      showing. This article specifically addresses those pruritic dermatoses caused by
      allergies, including food allergy/intolerance, atopy and contact allergy, as well
      as by two ectoparasites, stick-tight fleas and rhabditic mange. The clinical
      signs, diagnostic tests, and treatment recommendations are discussed for each
      disorder. Insect hypersensitivity and pruritus associated with the other more
      common ectoparasites are covered in depth elsewhere in this issue.

PMID- 7634156
TI  - Zonation of metabolism and gene expression in liver.

PMID- 7634160
TI  - Parasitic dermatoses that cause pruritus in horses.
AB  - Insect hypersensitivity is the most common cause of equine pruritus. It is a
      seasonal, highly pruritic dermatosis that is caused by the salivary antigens of
      biting insects. The most common insects are discussed in terms of the area of the
      horse affected, clinical signs, therapy, and preventative strategies.

PMID- 7634161
TI  - Internal diseases that have skin lesions.
AB  - Skin lesions can be associated with many internal diseases. Most organ systems
      seem to have conditions in which skin lesions can develop. Treatment of the skin
      lesions in such a situation is palliative. The underlying internal disease must
      be addressed for resolution of the skin lesions to occur. It is important to view
      the skin as an integral communicating part of the body and not just as the skin.

PMID- 7634162
TI  - Systemic/topical therapy.
AB  - Hopefully, the practitioner has obtained a basic broader knowledge of the options
      available for topical and systemic equine dermatologic therapy. There are many
      topical and systemic agents that can aid in the treatment of specific skin
      disease and there are safer alternatives to glucocorticoid therapy. Because
      equine dermatology is still in its infancy, there is still much to be learned.
      The practitioner is encouraged to pay close attention to this specialty because
      it will continue to evolve rapidly.

PMID- 7634163
TI  - Entomologic evaluation of insect hypersensitivity in horses.
AB  - Potential methods of incriminating insects as the cause of insect
      hypersensitivity are presented. A listing of the biting midges known to attack
      horses in North America is presented also. An example of how species may be
      determined to be the cause of the hypersensitivity is given using data from a
      recent study in Florida. Light trap collections indicated the temporal and
      geographic distribution of potential contributing species and collections made by
      vacuuming horses further delineated species by proving they feed on horses and
      the correct locations on the horses to match lesion distribution. Culicoides
      hypersensitivity in horses in Florida seems to be caused by a series of species
      active and feeding on the horses at different times of the year.

PMID- 7634164
TI  - An overview of equine dermatoses characterized by scaling and crusting.
AB  - Scaling and/or crusting are common clinical findings associated with equine skin
      diseases. Scaling and crusting may be associated with pruritic or nonpruritic
      dermatoses. This article focuses on those conditions that are usually nonpruritic
      in horses. They include the infectious dermatoses, the keratinization/seborrheic
      disorders, photosensitization, and the immunologic/inflammatory disorders,
      including pemphigus foliaceus, equine exfoliative eosinophilic dermatitis and
      stomatitis, and equine histiocytic dermatitis (sarcoidosis). Clinical signs that
      help differentiate the various disorders are given, and diagnostic and
      therapeutic options are discussed.

PMID- 7634165
TI  - Infectious crusting dermatoses.
AB  - Although there are numerous dermatoses in the horse in which the formation of
      crusts occurs, there are two relatively common and important infectious crusting
      dermatoses, namely, dermatophytosis and dermatophilosis. This article reviews the
      current concepts regarding the etiology and pathogenesis of each disease, as well
      as the more common clinical presentations, methods of diagnosis, and treatment.

PMID- 7634157
TI  - Heterogeneity of kinetic parameters of enzymes in situ in rat liver lobules.
AB  - In the present review, metabolic compartmentation in liver lobules is discussed
      as being dynamic and more complex than thus far assumed on the basis of numbers
      of mRNA or protein molecules or the capacity (zero-order activity) of enzymes.
      Isoenzyme distribution patterns and local kinetic parameters of enzymes may vary
      over the different zones of liver lobules. As a consequence, metabolic fluxes in
      vivo at physiological substrate concentrations may be completely different from
      those that are assumed on the basis of the number of molecules or the capacity of
      enzymes present in zones of liver lobules. For a more correct estimation of the
      levels of metabolic processes in the different compartments of liver tissue,
      local kinetic parameters and substrate concentrations have to be determined to
      calculate local metabolic fluxes. Direct measurements of metabolic fluxes in vivo
      with the use of noninvasive techniques is a promising alternative and the
      techniques will become increasingly important in future metabolic research.

PMID- 7634166
TI  - Overview of equine papular and nodular dermatoses.
AB  - Papules and nodules are common lesions on horses and have a variety of underlying
      causes. This article addresses inflammatory and congenital nodules primarily,
      including urticaria, erythema multiforme, those nodules caused by infectious
      agents, epidermoid and dermoid cysts, and the uniquely equine skin tumor, the
      sarcoid. The eosinophilic nodules and other tumors are covered elsewhere in this
      issue. Diagnostic and therapeutic approaches to each of the diseases are
      emphasized.

PMID- 7634167
TI  - Eosinophilic nodular dermatoses.
AB  - This article describes the etiology, clinical signs, diagnosis, and treatment of
      various equine nodular diseases. Although of different etiologies, this group of
      diseases shares a common histologic reaction pattern characterized by
      infiltration of eosinophils and collagen degeneration. Collagenolytic granuloma,
      axillary nodular necrosis, unilateral papular dermatosis/eosinophilic
      folliculitis, amyloidosis, habronemiasis, and mast cell tumors are discussed.

PMID- 7634168
TI  - Cutaneous pythiosis in the horse.
AB  - Pythiosis of horses in an invasive, ulcerative, proliferative, pyogranulomatous
      disease of the skin and subcutis caused by Pythium insidiosum, a fungus-like
      oomycete in the order Peronosporales of the kingdom Protista. Pythiosis is a form
      of "phycomycosis," which is a complex of pyogranulomatous diseases that also
      includes conidiobolomysosis, basidiobolobysosis, and disorders caused by members
      of the order Mucorales.

PMID- 7634169
TI  - Larry Scheving and cancer chronotherapy.

PMID- 7634170
TI  - Cytokinetic circadian patterns in human host and tumor.

PMID- 7634171
TI  - Circadian optimization of treatment time using DNA replication-dependent cell
      cycle-specific halogenated pyrimidines.

PMID- 7634172
TI  - Chronotherapy of growth factors.
AB  - Circadian coordination of the components of the hematopoietic system, immune
      system, and host-tumor balance in animals and humans have been demonstrated.
      Preclinical studies provide evidence that when within-the-day exogenous protein
      growth modulators such as EPO, G-CSF, IL-1, IL-2, TNF, or IFN are administered to
      animals, they determine to a large extent the magnitude of the hematopoietic,
      immunologic, toxic, and antitumor response. Optimal circadian timing of
      therapeutic proteins with minimal toxicity (e.g. EPO, CSF) should be further
      explored to investigate whether lower doses could be used or intervals prolonged
      with equal or greater drug efficacy. For antitumor efficacy, optimal circadian
      timing of growth factors may lower host toxicity, which may allow higher doses to
      be more safely utilized to more reliably induce significant anticancer activity.

PMID- 7634173
TI  - Time of day versus internal circadian timing references.

PMID- 7634174
TI  - Experimental basis for ciradian cancer chemotherapy.

PMID- 7634175
TI  - Clinical cancer chronotherapy trials: a review.
AB  - Experimental studies have documented that both toxicity and antitumor activity of
      cancer drugs are time dependent. The mechanism behind this observation is at
      least in part related to circadian changes in pharmacokinetics, pharmacodynamics,
      and DNA synthesis in both normal organs and tumors. The results of published
      studies designed to test chronotherapy in cancer patients are reviewed. The
      possible mechanisms behind the circadian-stage-dependent pharmacokinetics and
      pharmacodynamics are reviewed briefly for all drug classes but in detail for the
      fluoropyrimidines. Clinical trials have confirmed that both toxicity and
      achievable dose intensity for several cancer drugs are time dependent. Ongoing
      prospective randomized studies will determine whether this scheduling method
      impacts on response rate and overall survival in cancer patients.

PMID- 7634176
TI  - Cancer chronotherapy: is there a right time in the day to treat?
AB  - Cicadian variation in drug metabolism and tissue sensitivity to drugs impacts
      their activity and toxicity. A growing body of data suggests that therapy may be
      improved and toxicity reduced, by administering antineoplastic agents at
      carefully selected times of the day. This article gives background information
      that supports the predictable and exploitable nonlinear dynamic relationship
      between dose and effect that occurs each day, explores the ways in which clinical
      research must determine when to treat, wrestles with the question of the
      stability of circadian time structure in chronically ill cancer patients, and
      discusses the implications of the principles outlined to anticancer drug
      development.

PMID- 7634177
TI  - Theoretical and practical aspects of circadian coordination of host and tumor.

PMID- 7634178
TI  - Power spectral analysis of systemic arterial pressure signals during open heart
      surgery.
AB  - BACKGROUND: The close relationship between the balance of sympathetic and
      parasympathetic tones and the results of power spectral analysis (PSA) of
      systemic arterial pressure (SAP) has been suggested recently. The purpose of this
      study was to further describe the changes of balance between the two autonomic
      nervous components during open heart surgery for coronary arterial disease (CAD)
      or valvular heart disease (VHD) with the PSA technique of SAP. METHODS: By
      relaying the SAP signals to a personal computer utilizing a power spectral
      analysis algorithm, radial arterial pressure signals of 27 patients (11 with CAD
      for coronary artrial bypass graft, as CAD groups; 16 with VHD, as VHD group,
      including 8 for aortic valve replacement and 8 for mitral valve replacement)
      during open heart surgery were monitored in a continuous, on-line and real-time
      manner. On-line power spectral analysis was performed according to the five
      different stages of the operation. RESULTS: Power density tended to increase in
      the high frequency (HF) band during the ventilator-supported stages of the open
      heart procedures, i.e., the pre-cardiopulmonary bypass (CPB) and the off-CPB
      periods. The power density in other frequency bands during the whole course of
      general anesthesia otherwise decreased significantly, with the lowest values
      occurring during CPB. The power density in very low frequency (VLF) band was much
      higher than in other bands during CPB, and became the major component of total
      power density in this period. CONCLUSIONS: The balance between sympathetic and
      parasympathetic components of autonomic nervous system changes rapidly during
      open heart surgery and needs careful monitoring. By utilizing PSA of SAP,
      mathematical error might be an obstacle of using LF:HF ratio as an index of
      autonomic balance during the CPB period when the HF density approaches zero.

PMID- 7634179
TI  - Evaluation of a rapid microfiltration test for detection of HIV-1 antibody in
      serum.
AB  - BACKGROUND: Since the number of asymptomatic Human Immunodeficiency Virus Type 1
      (HIV-1) infections has increased rapidly recently, to detect HIV-1 antibody
      rapidly becomes very critical when a quick mass survey is required or especially
      badly injured persons need blood transfusions immediately. This study evaluated
      sensitivity and specificity of a 10-minute qualitative assay (Single Used
      Diagnosis System; SUDS HIV-1 test) which is performed in a plastic cartridge
      using a modified enzyme immunoassay and to compare the results so obtained with
      more conventional HIV-1 antibody detection systems. METHODS: A total number of
      248 human serum samples collected at several local hospitals and health stations
      were delivered to this Institute from June 1993 to April 1994 for confirmation
      were used to compare results obtained by either particle agglutination (PA),
      Western blot, or the SUDS HIV-1 tests. RESULTS: High sensitivity and specificity
      of SUDS were achieved using the conjugation of a specific gag antigen of HIV-1
      and a synthetic HIV-1 envelop peptide. There was good correlation to one another
      among results from all the three tests. CONCLUSIONS: Data from those three tests
      employed in this study revealed no significant differences in sensitivity and
      specificity. The simplicity and rapidity of the SUDS make it more suitable for
      use than the others, especially when an emergency room screening test or a blood
      bank test is required where urgent situations need urgent answers.

PMID- 7634180
TI  - Comparison and correlation of measurements of glomerular filtration rates by Tc
      99m DTPA and 24-hour creatinine clearance.
AB  - BACKGROUND: The measurement of 24-hour creatinine clearance (CCr) is most
      commonly used to estimate glomerular filtration rate (GFR). A new rapid method
      for determining GFR by radionuclide compound Tc-99m diethylenetriamine
      pentaacetic acid (DTPA) has been developed and widely used in the last decade.
      The purpose of this study is to compare and correlate the measurements of GFR by
      the two method. METHODS: The present series included 6 normal volunteer
      outpatients and 49 hospitalized patients with various degrees of renal
      dysfunction who were studied at Taichung Veterans General Hospital from June 1985
      to June 1986. All patients underwent both Tc-99m DTPA GFR and 24-hour CCr. Tc-99m
      DTPA computed GFR was calculated using the formula of Gates. RESULTS: The
      radionuclide computed GFR for each subject was compared with his or her 24-hour
      CCr. The correlation coefficient (r) was 0.89 with p < 0.001. The subjects were
      divided into two groups. Group A consisted of 6 normal volunteers and 14 patients
      with serum creatinine less than 1.4 mg/dl (creatinine: normal range 0.7 to 1.4
      mg/dl). Group B consisted of 35 patients with serum creatinine greater than 1.4
      mg/dl. Group B was further divided into Subgroup 1 with serum creatainine from
      1.4 to 10 mg/dl, and Subgroup 2 with serum creatinine above 10 mg/dl. There was
      good correlation and less absolute error between DTPA-GFR and CCr in Group A and
      Subgroup 1. The results suggest that, when serum creatinine is less than 10
      mg/dl, either DTPA or CCr is a good method for detection of GFR. CONCLUSIONS:
      DTPA-GFR measurement using this radionuclide technique has shown good correlation
      with CCr when serum creatinine is under 10 mg/dl. In patients with renal
      impairment and with serum creatinine above 10 mg/dl, neither examination is
      reliable. A more sensitive test to evaluate GFR in severe renal impairment is
      required for further investigation.

PMID- 7634181
TI  - Clinical values of CA19-9, CA125 and CEA in malignant obstructive jaundice.
AB  - BACKGROUND: Serum CA19-9, CA125 and CEA are glycoproteic tumor markers and they
      have been used for detecting patients with pancreatobiliary diseases in whom
      obstructive jaundice is common. This study was designed to investigate whether
      cholestasis may interfere with the clinical application of these tumor markers or
      not. METHODS: Radioimmunoassay for serum CA19-9, CA125 and carcinoembryonic
      antigen (CEA) was obtained from 86 patients with hyperbilirubinemia, including 50
      patients with malignant jaundice (pancreatic carcinoma 20, biliary tract
      carcinoma 30) and 36 patients with benign jaundice (choledocholithiasis 33, acute
      cholangitis 3). Clinical follow-up for the utility of these markers on the
      patients with obstructive jaundice was conducted. RESULTS: In patients with
      malignant jaundice, higher positive rates of CA19-9 (94% vs 56%, p < 0.01), CA125
      (52% vs 17%, p < 0.01) and CEA (42% vs 6%, p < 0.01) than in those with benign
      jaundice were found. In diagnosis of malignant tumors, sensitivity was superior
      in CA19-9 (94%) than in CA125 (52%) and CEA (42%), but the latter two had higher
      specificities (83% and 95%). In malignant jaundice, elevated serum bilirubin
      levels were correlated with CA125 (r = 0.34, p < 0.05) but not with CA19-9
      levels. In benign jaundice, serum bilirubin were correlated with CA19-9 (r =
      0.58, p < 0.001) and CA125 (r = 0.45, p < 0.01) levels. The correlation between
      serum bilirubin and CEA levels was not significant in either group. After
      effective drainage, all markers decreased significantly in patients with benign
      jaundice but not in those with malignant diseases. CONCLUSIONS: Elevated serum
      CA19-9, CA125 and CEA levels were observed in both benign and malignant
      pancreatobiliary diseases with obstructive jaundice. Longitudinal follow-up of
      these markers and other complementary studies are essential for diagnosis of
      malignant tumors when cholestasis is present.

PMID- 7634182
TI  - Effect of oral erythromycin on patients with diabetic gastroparesis.
AB  - BACKGROUND: Abnormal gastrointestinal motility is a well recognized complication
      of diabetes mellitus, and disordered gastric emptying may hamper glycemic
      control. The objects of this study were to investigate the effect of oral
      erythromycin on gastric emptying and to evaluate the effect of corrected gastric
      emptying on glycemic control in patients with diabetic gastroparesis. METHODS:
      Twenty patients of Type II (non-insulin-dependent) diabetes mellitus with typical
      symptoms of gastroparesis and delayed solid phase gastric emptying were studied.
      There were 18 males and 2 females, aged 49 to 72 years. Erythromycin
      (erythromycin estolate) was given orally at a dose of 250 mg, 3 times daily, 30
      minutes before each meal. Radionuclide-labelled solid phase gastric emptying and
      fasting blood sugar (FBS) were studied after one day of erythromycin therapy, and
      again after 2 weeks of the therapy. The half time of gastric emptying (GETt1/2)
      represented the time needed for 50 percent of the initial radioactivity to leave
      the stomach, and was used to express the gastric emptying status. RESULTS: The
      GETt1/2 decreased from 198.0 +/- 58.9 minutes at baseline to 139.1 +/- 67.6
      minutes following one day of erythromycin therapy (p < 0.01), and to 137.1 +/-
      71.2 minutes after two weeks of treatment (vs. baseline p < 0.01). The FBS
      decreased from 159.0 +/- 40.2 mg/dl at baseline to 149.0 +/- 38.5 mg/dl following
      one day of therapy (p = 0.12, NS), and to 139.2 +/- 39.8 mg/dl after two weeks of
      treatment (vs. baseline p < 0.02). CONCLUSIONS: It was concluded that
      erythromycin is an effective prokinetic agent for diabetic gastroparesis, and
      that corrected gastric emptying may improve glycemic control.

PMID- 7634183
TI  - Comparison of human menopausal gonadotropin and follicle-stimulating hormone with
      gonadotropin-releasing hormone agonist desensitization for controlled ovarian
      hyperstimulation in in vitro fertilization.
AB  - BACKGROUND: A pregnancy in patients treated with gonadotropin-releasing hormone
      agonists (GnRHa) using follicle-stimulating hormone (FSH) alone was first
      reported by Shaw et al. in 1991. Recently, several comparative trials have shown
      that FSH is as effective as human menopausal gonadotropin (hMG) in this
      indication. In other words, the residual endogenous levels of luteinizing hormone
      (LH) in GnRHa treated cycles may be generally sufficient to support FSH-induced
      follicular development to exempt from the co-administration of exogenous LH.
      METHODS: A total of 42 consecutive candidates for in vitro fertilization (IVF)
      participated in a prospective randomized study. In this study, the efficacy of
      two different gonadotropins (Pergonal and Metrodin, Serono, Italy) in inducing
      ovulation was investigated. All treated women were less than 40 years of age and
      had received a long desensitized protocol by a GnRHa (Leuprolide acetate, Takeda
      or Decapeptyl, Ferring). Ovarian inactivity was monitored by plasma estradiol and
      LH concentration. After the pituitary gland was down-regulated, all patients were
      given either hMG (n = 25) or FSH (n = 17) for controlled ovarian hyperstimulation
      (COH). RESULTS: The mean number of gonadotropin ampoules and the peak estradiol
      level were significantly higher in hMG group than in the FSH group. No
      significant differences were found between both groups in the incidence of
      cancelled cycles, failed oocyte recovery, mean number of oocytes recovered per
      patient, the fertilization and embryo cleavage-rate. However, the hMG group
      demonstrated a higher pregnancy and abortion rate. CONCLUSIONS: There is no
      significant difference between hMG and FSH stimulation when used following GnRHa
      desensitization for COH, so the cost should be considered.

PMID- 7634184
TI  - A 12-year survey of 681 ectopic pregnancies.
AB  - BACKGROUND: Since 1970, incidence of ectopic pregnancy has increased nearly three
      fold worldwide. Ectopic gestation is the most common cause of mortality
      associated with pregnancy in the first trimester, and may adversely affect
      subsequent fertility. METHODS: A total of 681 patients with ectopic pregnancies
      seen during a 12-year span were analyzed for clinical evaluations including
      etiology, diagnosis and therapy. RESULTS: The ratio of ectopic pregnancies to
      deliveries was 1:52. The largest figure occurring in multiparous patients was in
      the 26 to 30 year age bracket. A previous abdominal operation or previous
      antibiotic therapy substantiating antecedent pelvic inflammatory disease is a
      prime etiologic factor in ectopic pregnancy. The most significant physical
      finding was abdominal or rebounding tenderness associated with adnexal or cul-de
      sac fullness. The diagnosis was initiated by urine beta-hCG (ELISA) or serum beta
      hCG (RIA) and ultrasonography in the majority of patients. Nighty-three percent
      of ectopic pregnancies were tubal pregnancies, and therapy consisted primarily of
      total salpingectomy. There were no maternal deaths in this series. CONCLUSIONS:
      Although newer diagnostic modalities are becoming more common, a correct
      diagnosis of ectopic pregnancy still relies heavily on clinical signs and
      symptoms. After a correct diagnosis is made, conservative surgical treatment or
      chemotherapy with preservation of the tube is the first choice for treatment.
      Thus to achieve a higher potential for a later pregnancy in the future for these
      women, routine salpingectomy should be the last resort.

PMID- 7634186
TI  - Cutaneous manifestation of Kikuchi's disease: a case report.
AB  - A 22-year-old male was admitted with a 1-month history of chills, fever, multiple
      skin eruption and painless lymphadenopathy. He has later been confirmed by
      typical histopathological findings to be a case of Kikuchi's histiocytic
      necrotizing lymphadenitis. Extranodal involvement with skin manifestation in
      Kikuchi's disease has rarely been reported; herein this unusual case is
      described.

PMID- 7634185
TI  - Primary uncommon malignant tumors of the esophagus: an analysis of 30 cases.
AB  - BACKGROUND: Uncommon malignant tumors of the esophagus are defined as any
      histological type of malignant esophageal tumors other than the typical squamous
      cell carcinoma. Their biological characteristics remain obscure because of their
      rarity. Thus, this is a retrospective review of patients here with uncommon
      esophageal cancers in an attempt to evaluate their prognostic factors and proper
      therapeutic modalities. METHODS: Among 1,674 patients with esophageal cancers,
      only 30 (1.8%) with uncommon esophageal cancers were collected between 1977 and
      1992. The clinical parameters for evaluation consisted of age, sex, histological
      type, location, staging and a variety of therapeutic management techniques and
      their results. RESULTS: Histologically, there were 10 adenocarcinomas, 7 small
      cell carcinomas, 6 adenosquamous carcinomas, 3 carcinosarcomas, 1 mucoepidermoid
      carcinoma, 1 adenoid cystic carcinoma, 1 fibrosarcoma, and 1 basal cell
      carcinoma. The mean age was 65.8 years, ranging from 46 to 85 years. Upon
      admission to hospital, the most common clinical symptoms included dysphagia, body
      weight loss and substernal pain. The tumor staging, according to TNM
      classification was evaluated as follows: Stage I: 13.3%, Stage II: 46.7%, Stage
      III: 16.9%, Stage IV: 23.3%. The middle third thoracic esophagus was the most
      common location of tumor occurrence. Overall one-year, two-year, and five-year
      survival rates were 39.3%, 21.4%, and 10.7% respectively. These results were as
      poor as those of squamous cell carcinoma. However, the patients with Stage I and
      Stage II tumors (mean, 23.8 months) had significantly better survivals than those
      with Stage III and Stage IV (mean, 3.9 months). Furthermore, if the tumor was
      resectable, the patients undergoing esophagectomy had much better one-year and
      two-year survival rates than those without esophagectomy (p < 0.01). In addition,
      patients with small cell carcinoma seemed to have worse treatment outcome than
      those with other histological types of tumors. CONCLUSIONS: These results
      suggested that key factors contributing to prognosis included tumor staging as
      well as respectability. Thus, it is recommended that, with early detection and
      diagnosis, esophagectomy might be the treatment-of-choice in managing these
      uncommon esophageal malignancies. Adjuvant therapy including irradiation and
      chemotherapy may be helpful, particular for small cell carcinoma.

PMID- 7634187
TI  - Pulmonary gangrene: a case report.
AB  - Pulmonary gangrene is a rare complication of severe pulmonary infection in which
      a pulmonary segment or lobe is sloughed. In the English literature, pulmonary
      gangrene secondary to bacterial infection is uncommon, and fewer to other
      etiologies. Characteristic roentgen patterns of a mass within a cavity is the
      hallmark of this disease, which differentiates from a lung abscess. Some authors
      have emphasized that surgical resection of the infected lobe is the principal
      option of treatment. In contrast, some have advocated that patients with
      pulmonary gangrene can be managed with medical therapy. Recently we successfully
      treated a case of pulmonary gangrene with appropriate antibiotics and
      percutaneous small bore catheter drainage, even though the complication of
      bronchopleural fistula was encountered, which led to prolonged hospitalization.
      The serial roentgenograms and the pictures of computed tomography (CT) will be
      demonstrated.

PMID- 7634188
TI  - Isolated resection of proper caudate lobe for hepatocellular carcinoma in
      cirrhotic liver: a case report.
AB  - The caudate lobe of the liver is located between the hepatic hilum and the
      inferior vena cava. Resection of the caudate lobe alone, without sacrificing
      other parts of the liver, is a surgical challenge. An isolated resection of
      proper caudate lobe was accomplished here in a 64-year-old man with
      hepatocellular carcinoma complicated by liver cirrhosis. The post-operative
      course was uneventful. The patient remains free of disease two years after
      operation. The technique used is described to advocate isolated caudate lobectomy
      for a patient with cirrhosis with a caudate lobe hepatocellular carcinoma.

PMID- 7634189
TI  - Posterior urethral valves: a report of five cases.
AB  - From 1985 to 1993, five male patients with posterior urethral valves were treated
      at our hospital; they included three newborns, a 32-month-old and a 10-year-old
      child. On initial examination, all patients showed severe bilateral
      hydronephrosis and hydroureter on sonographic findings, dilatation of the
      prostate urethra and trabeculation of the bladder wall in the voiding
      cystourethrogram; only one patient showed vesicoureteral reflux. Type I urethral
      valves were present in all patients. Retrograde transurethral ablation of the
      valves was performed in four patients with good preoperative renal function. The
      postoperative courses were smooth except for vesicoureteral reflux in one patient
      and systemic fungus infection in another. Reimplantation of the ureter was done
      for the vesicoureteral reflux, and the fungus infection was treated by
      amphotericin B. Cutaneous vesicostomy was performed for a newborn since the
      urethral orifice was small. He presented with poor renal function and ascites.
      Delayed antegrade ablation of the valves per vesicostomy and closure of the
      vesicostomy were done three months later after restoration of the renal function.
      Renal function returned to normal after operation in all patients, but the
      function of the upper urinary tract and bladder continence need long-term follow
      up.

PMID- 7634190
TI  - Cerebral phaeohyphomycosis complicated with brain abscess: a case report.
AB  - Cerebral phaeohyphomycosis is used to describe the rare clinical syndrome of
      cerebral infection caused by dematiaceous (i.e. pigmented olivaceous-brown)
      fungi. It usually presents as brain abscess. In view of the rarity of this fungal
      infection and its clinical importance, we report a case of cerebral
      phaeohyphomycosis caused by Xylohypha bantiana. The patient presented with a
      seizure attack. The MRI study revealed a ring-enhancing lesion with marked
      perifocal edema in right high frontoparietal junction of the brain. He underwent
      an initial craniotomy for removal of the lesion and a second craniotomy for
      recurrence of the lesion 3 months later. The diagnosis was based on successful
      cultivation of X. bantiana from the surgical specimen and on histopathology. The
      patient received antifungal drug therapy of 5-flucytosine and itraconazole. He
      has done well without any symptoms. We think complete surgical removal of the
      brain abscess combined with antifungal drug therapy is the best management for
      this rare fungal disease.

PMID- 7634191
TI  - Vertebral artery dissection complicated by cervical manipulation: a case report.
AB  - A 32-year-old healthy man developed vomiting, blurred vision, and consciousness
      disturbance following cervical manipulation. Physical examination showed
      stuporous consciousness and spontaneous horizontal nystagmus. Computed tomography
      (CT) and magnetic resonance (MR) imaging of the brain revealed infarction in the
      territory of the basilar artery. Studies of MR angiography and vertebral
      angiography disclosed dissection of the right vertebral artery at the
      atlantoaxial segment. Antiedematous drugs were prescribed and the patient
      gradually improved. Neurologic examination six months later demonstrated mild
      cerebellar ataxia. Physicians and patients should be aware that vertebro-basilar
      dissection may follow cervical manipulation, and, more importantly, should
      attempt to prevent progressive infarction.

PMID- 7634192
TI  - Fractures of the tibial diaphysis: is closed locked intramedullary nailing the
      right answer?

PMID- 7634193
TI  - Plus ca change, plus c'est la meme chose: Canadian medical officers in Bosnia and
      the Second World War.

PMID- 7634194
TI  - Diagnostic manoeuvres in patients with respiratory failure.

PMID- 7634195
TI  - Radiology for the surgeon. Case 4. Thorotrast-induced malignancy of liver.

PMID- 7634196
TI  - Routine predeposit of autologous blood is not warranted before breast reduction
      surgery.
AB  - OBJECTIVE: To assess perioperative blood losses and transfusion requirements in
      patients who undergo breast reduction surgery and to gauge the impact of an
      autologous blood program on homologous transfusion requirements. DESIGN: A chart
      review of patients who underwent breast reduction surgery between 1988 and 1992.
      SETTING: The Ottawa General Hospital, a teaching hospital with a surgical
      training program but with no plastic surgery program. PATIENTS: Included in the
      review were all 153 patients who had breast reduction surgery during the study
      period. Twenty patients were excluded because either the predonation or the final
      hemoglobin concentration was not available. The remaining 133 patients were
      divided into three groups: group 1--patients who had not predonated blood (63);
      group 2--patients who predonated blood and received a transfusion (55); and group
      3--patients who had predonated blood but did not receive a transfusion (15). MAIN
      OUTCOME MEASURES: The mean final hemoglobin concentrations, the number of
      patients who lost more than 30 g/L of hemoglobin and the requirements for
      homologous transfusions. RESULTS: The rate of homologous transfusion was 1%
      whether the patients had predonated blood or not. If a more restricted pattern of
      transfusion been used this rate would have been lower. The final hemoglobin
      concentration was similar in all three groups. More patients in group 3 (60%)
      lost more than 30 g/L of hemoglobin compared with the initial hemoglobin value
      than either group 1 (23%) or group 2 (20%) (p < 0.01). CONCLUSION: The routine
      inclusion in autologous blood programs of patients scheduled to undergo breast
      reduction surgery is not warranted.

PMID- 7634197
TI  - Benefit of open lung biopsy in patients with respiratory failure.
AB  - OBJECTIVE: To determine the benefit of open lung biopsy (OLB) in patients with
      respiratory failure in whom medical therapy is unsuccessful. DESIGN: A
      retrospective case series. SETTING: A tertiary care centre. PATIENTS: Thirty-one
      patients (20 men, 11 women, mean age 55 years) without the human immunodeficiency
      virus or AIDS who were suffering from respiratory failure. INTERVENTION: OLB
      through a limited anterior thoracotomy. MAIN OUTCOME MEASURES: Diagnosis, change
      in therapy, timing of OLB, immune status, survival. RESULTS: A specific diagnosis
      was made in 68% of patients, and nonspecific pulmonary fibrosis was found in 32%.
      Eighteen patients (59%) had a change in therapy: 11 had new therapy and 7 had
      medical therapy withdrawn because of irreversible disease. There was a
      significant (p = 0.012) improvement in survival in those who had OLB early
      compared with those who had OLB later in the course of the disease (70% versus
      14%). There was a significant (p = 0.026) difference in the proportion of
      specific diagnoses made among those who had OLB early compared with those who had
      it later (100% versus 52%). A significant (p = 0.18) improvement in survival was
      noted in those who had new therapy instituted as a result of early OLB compared
      with late OLB (86% versus 25%). Patients not immunocompromised before OLB had a
      significantly (p = 0.02) better survival rate than those who were
      immunocompromised. CONCLUSIONS: The duration of respiratory failure before OLB
      and the immune status were associated with improved survival in patients with
      respiratory failure and unsuccessful medical therapy. This was not directly
      attributable to changes in therapy after OLB. However, five survived as a direct
      result of therapy instituted after OLB and seven were spared needless therapy
      when irreversible disease was found. Overall survival may not be altered by OLB,
      but individual clinical benefit may be seen in nearly 40% of patients.

PMID- 7634198
TI  - The gelweave polyester arterial prosthesis.
AB  - OBJECTIVE: To determine the effect of the gelatin coating on the efficacy of
      Gelweave, a new gelatin-sealed woven polyester graft material, as an arterial
      prosthesis. DESIGN: In-vitro and in-vivo studies of the prosthesis. SETTING: A
      laboratory of experimental surgery in a university teaching institution.
      SUBJECTS: After in-vitro testing of the material, eight dogs were subjected to a
      series of in-vivo tests to evaluate the properties of Gelweave in comparison with
      its unsealed precursor and a commerically available collagen-coated woven
      polyester prosthesis. INTERVENTION: Implantation of the prosthesis as a
      thoracoabdominal bypass for prescheduled periods ranging from 4 hours to 6
      months. MAIN OUTCOME MEASURES: Physical and chemical properties of the virgin
      prosthesis compared with the other two prostheses, effects of the gelatin-sealed
      prosthesis on healing, the hematologic characteristics of the dogs before
      operation and at sacrifice, microscopic studies, fibrin and platelet uptakes,
      prostaglandin secretion, and properties of the Gelweave grafts removed at varying
      periods after implantation. RESULTS: The gelatin sealant in the Gelweave
      prosthesis effectively reduced the water permeability of the new prototype to
      zero. Neither blood loss at implantation nor infection during the
      postimplantation period was observed. The gelatin impregnation did not cause any
      adverse response in the dogs and was completely lysed within 2 weeks, thus
      allowing encapsulation and graft healing to progress satisfactorily. After 2
      weeks, the prostacyclin:thromboxane ratio was greater than 1.0, whereas the
      fibrin and platelet uptakes on the luminal surface of the Gelweave grafts
      remained low, regardless of the period of implantation. Analysis of the explanted
      grafts confirmed that this gelatin-sealed prototype prosthesis healed
      satisfactorily and no adverse biologic response occurred as a result of the
      gelatin coating. It maintained its biostability during 6 months in situ.
      CONCLUSION: The new Gelweave arterial prosthesis is ready for clinical use as a
      thoracic and abdominal vascular substitute.

PMID- 7634199
TI  - Educating tomorrow's cardiac and thoracic surgeons: a Canadian initiative.
AB  - Societal, technologic, organizational and educational developments during the
      past 10 years have brought about increasing promises for change in the graduate
      medical education of cardiac and thoracic surgeons. These changes effectively
      lengthened training to 8'years and created a double standard for the education of
      a thoracic surgeon. A task force mandated by the Royal College of Physicians and
      Surgeons of Canada nucleus committees in both cardiac and thoracic surgery and
      with the support of the Canadian Society of Cardiovascular and Thoracic Surgeons
      studied the problem and made the following recommendation: cardiac surgery and
      thoracic surgery should each become a primary specialty with its own nucleus
      committee. Each specialty would require 6'years' training, with the possibility
      of obtaining certification in both specialties after an additional 18'months
      training. Each specialty could also be entered after completion of full training
      in general surgery. The task force also urged the development of a curriculum to
      guide educational objectives in each specialty. These changes will produce a
      flexible, shorter, more focused program for cardiac and thoracic surgeons for
      both university and community settings.

PMID- 7634200
TI  - Modern war surgery: the experience of Bosnia. 2: The clinical experience.
AB  - A Canadian field surgical hospital was deployed in the former Yugoslavia to
      support the medical needs of Canadian and other United Nations troops. Over a 6
      month period, 5661 patients were seen and 50 surgical procedures performed.
      Gunshot, shrapnel and other blast injuries were responsible for the injury in
      only 10 patients seen at the hospital. Strict adherence to the concepts of
      hygiene, safety and trauma prevention is essential for the proper health care of
      large groups of peacekeepers abroad. Civilian involvement was limited by
      political restrictions, but a few civilians were helped. The ability to provide
      modern medicine in the field of battle boosted the morale of the Canadian troops.

PMID- 7634201
TI  - Management of cystic lesions of the tail of the pancreas.
AB  - OBJECTIVE: To emphasize that although cystic pancreatic neoplasms are stated to
      make up only 10% of pancreatic cysts, this number may be significantly higher if
      patients who are misdiagnosed with pseudocysts are considered. DESIGN: A small
      case series. SETTING: A tertiary-care centre. PATIENTS: A consecutive sample of
      three patients with cystic lesions of the tail of the pancreas seen between 1992
      and 1994. All three were women ranging in age from 28 to 42 years. Two had been
      treated previously for pancreatic pseudocysts by cystenterostomy. None had a
      history of pancreatitis or alcohol abuse, and gallstones were not present on
      ultrasonography. INTERVENTIONS: Distal pancreactectomy and splenectomy. RESULTS:
      The excised specimens from the two patients treated initially elsewhere revealed
      mucinous cystadenoma with atypia in one and mucinous cystadenocarcinoma with
      invasion into stomach in the other. In the third patient, a cystic neuroendocrine
      tumour and two other intrapancreatic nodules of neuroendocrine tumour were found
      on pathological examination. CONCLUSIONS: Pancreatic neoplasms may be
      misdiagnosed as pancreatic pseudocysts. In patients without a history or risk
      factors for pancreatitis, a cystic pancreatic mass is not necessarily a
      pseudocyst, and such patients should be considered for pancreatic resection.

PMID- 7634202
TI  - Clinical abnormalities in adults with pancreaticobiliary maljunction with and
      without bile-duct dilatation.
AB  - OBJECTIVE: To study clinical diseases associated with pancreaticobiliary
      maljunction with or without bile-duct dilatation. DESIGN: A retrospective study
      over 16 years. SETTING: A single university surgical service in Japan. PATIENTS:
      Thirty-three patients with pancreaticobiliary maljunction. MAIN OUTCOME MEASURES:
      Gallstones and cancer in patients with and without bile-duct dilatation. RESULTS:
      Twenty-five patients had dilatation of the bile duct, 8 did not. Seven (28%) of
      the 25 patients with bile-duct dilatation had gallstones compared with 1 (12%) of
      the 8 patients with no dilatation. Seven (88%) of the 8 patients with no
      dilatation had carcinoma (all of the gallbladder), but only 3 (12%) of the 25
      patients with bile-duct dilatation had carcinoma (1 of the gallbladder, 2 of the
      bile duct). CONCLUSION: Prophylactic cholecystectomy is recommended for patients
      with pancreaticobiliary maljunction and no dilatation of the bile duct because of
      the high incidence of gallbladder cancer.

PMID- 7634203
TI  - [Closed intramedullary nailing of tibial shaft fractures].
AB  - OBJECTIVE: To assess patient outcome after nailing of the tibial shaft with the
      unreamed AO/ASIF nail. DESIGN: A retrospective study of 54 nailed fractures of
      the tibial shaft treated between 1990 and 1994. Follow-up was done at the
      outpatient clinic and included measurements of the lower limbs and x-rays.
      SETTING: The study was conducted at the Hopital de l'Enfant-Jesus, Quebec, a
      centre specializing in trauma care. PATIENTS: Fifty-four acute displaced
      fractures of the tibial shaft occurring in 52 patients were studied.
      INTERVENTION: Nailing with the Synthes AO/ASIF unreamed locked nails. MAIN
      OUTCOME MEASURES: Time to bone fusion, rate of infection, incidence of deformity
      and failure rate of the implants, especially the lock screws. RESULTS: The
      majority of fractures were associated with a high-speed trauma (40/54 or 74% of
      cases) and 18 (33%) were open fractures. Osteitis developed in one (1.8%) open
      type IIIA fracture. Bone fusion was observed clinically and radiologically after
      29 weeks on average; none of the fractures presented residual deformity on
      rotation of more than 5 degrees or a difference in length of more than 1 cm or a
      frontal or sagittal displacement of more than 10 degrees. A single case of
      pseudoarthrosis was noted. One or more lock screws became deformed or broke in 16
      (34%) tibias; however, this did not lead to any reduction loss. Four compartment
      syndromes were diagnosed. CONCLUSIONS: Excellent results were obtained with
      respect to limb alignment and length. Loss of joint mobility was minimal. The
      number of lock screw failures indicates that a delayed weight bearing could
      prevent this complication, especially when an interfragment space remains after
      the nail placement.

PMID- 7634204
TI  - Emergency embolization of a ruptured aneurysm of the pancreaticoduodenal arcade.
AB  - Inferior pancreaticoduodenal aneurysms are uncommon. A 77-year-old woman was seen
      with a 1-week history of sharp pain in the right lower abdominal quadrant
      radiating to the back, associated with malaise, anorexia, vomiting and nonbloody
      diarrhea. Appendicitis was diagnosed, but at laparotomy a large retroperitoneal
      hematoma was found; no aneurysm was identified. The abdomen was closed and
      aortography was done. An aneurysm of the inferior pancreaticoduodenal artery
      arcade was demonstrated, with occlusion of the celiac artery at its origin. The
      arc of Buehler was patent and enlarged and supplied the hepatic and splenic
      arteries. Embolization with Gianturco coils placed proximal to the aneurysm was
      successful.

PMID- 7634205
TI  - Giant synovial cyst of the hip: an unusual presentation with compression of the
      femoral vessels.
AB  - A case of synovial cyst of the hip with symptomatic compression of the femoral
      vessels is described. A 75-year-old woman with severe unilateral osteoarthritis
      of the right hip was referred because of an intermittent, unpleasant sensation of
      coolness in the right foot and hip pain. A large mass was palpable in the femoral
      triangle. Computed tomography and arthrography revealed a large cyst
      communicating with the hip joint and compressing the femoral vessels ventrally.
      Total hip arthroplasty was carried out, and the stalk communicating with the cyst
      was ligated and divided. The unpleasant sensation of coolness in the right foot
      disappeared postoperatively. The authors concluded that iliopsoas bursitis should
      be considered in the evaluation of a patient with nonspecific pelvic or groin
      pain. As demonstrated in this rare case, the main symptom may be misleading and
      the typical syndrome of a tender groin mass with an underlying history of
      rheumatoid arthritis may be absent. Treatment should be directed to the
      underlying joint disease.

PMID- 7634206
TI  - Tarsal tunnel syndrome: an unusual case resulting from an intraneural
      degenerative cyst.
AB  - Multiple local and systemic entities have been implicated as causes of tarsal
      tunnel syndrome. In this report, a 31-year-old man presented with medial plantar
      nerve compression caused by an intraneural degenerative cyst of the posterior
      tibial nerve. Removal of the cyst and decompression of the nerve relieved his
      symptoms. This is the first time that such an entity has been reported as a cause
      of tarsal tunnel syndrome.

PMID- 7634207
TI  - Trans-scrotal intra-abdominal injuries: two case reports.
AB  - Penetrating injury to the scrotum is uncommon. Usually not serious in itself it
      may be associated with other more serious conditions. A 15-year-old boy was
      involved in a tobogganing accident, and a shard of wood penetrated the left
      scrotum, the anterior abdominal wall and the rectus sheath one-third of the way
      from umbilicus to xiphisternum. There was also a liver laceration. Removal of the
      piece of wood and closure of the wounds with drainage resulted in successful
      recovery. A 45-year-old man, sustained a penetrating straddle-type injury from a
      broom handle. The handle penetrated Dartos fascia but there was no testicular
      injury. It also perforated the rectus sheath 6 cm inferior to the costal margin,
      and both anterior and posterior gastric walls. The tract of the handle extended
      along the base of the transverse mesocolon and posterior to the pancreas. The
      perforations were debrided and repaired. The patient received a 5-day course of
      broad-spectrum antibiotics and recovered fully. As a result of their experience
      with these two patients the authors recommend that when there is penetration of
      Dartos fascia, the testicle and cord should be inspected, lavage and debridement
      should be carried out, and any foreign bodies should be removed and the injuries
      repaired. Antibiotics should be given perioperatively. In all cases the entire
      tract should be explored to its terminus to search for other injuries. Even upper
      abdominal injuries can occur with penetrating scrotal injuries.

PMID- 7634208
TI  - Thoughts of a second world war medical officer: a memoir.

PMID- 7634210
TI  - Giant peritoneal mouse.

PMID- 7634209
TI  - Total hip replacement in a limb severely affected by paralytic poliomyelitis.

PMID- 7634211
TI  - 64th Annual meeting of the Royal College of Physicians and Surgeons of Canada.
      Montreal, Quebec, September 13-18, 1995. Abstracts.

PMID- 7634212
TI  - Blood lead levels in children: conclusions questioned.

PMID- 7634213
TI  - Scepticism about Irlen filters to treat learning disabilities.

PMID- 7634215
TI  - New meanings for old quotation.

PMID- 7634214
TI  - Physician mobility: not black and white.

PMID- 7634216
TI  - Interaction between physicians and the pharmaceutical industry.

PMID- 7634218
TI  - Vaccination status of infants discharged from a neonatal intensive care unit.
AB  - OBJECTIVE: To determine the vaccination rate among infants discharged from a
      neonatal intensive care unit (NICU) and factors affecting that rate. DESIGN:
      Cross-sectional survey conducted when the children were 12 to 18 months of age.
      SETTING: NICU at the Royal University Hospital, Saskatoon, Sask. PARTICIPANTS:
      All 395 infants discharged from the NICU between Jan. 1 and June 30, 1992. MAIN
      OUTCOME MEASURES: Vaccination rate, ethnic background (native or non-native),
      place of residence (urban or rural), health status (number of days spent in the
      NICU), reasons for delay in or incomplete vaccinations (those involving parents'
      responsibility, infant illness or contraindications). RESULTS: Of the 395
      infants, 20 (5.0%) had died and incomplete information was available for 30
      (7.6%). Complete data were available for 345 (87.3%). Of the infants for whom
      data were available, 8 (2.3%) had never been vaccinated and 142 (41.2%) had a
      delayed vaccination schedule or had not completed their scheduled vaccinations.
      Only 195 (56.6%) of the infants had received a full vaccination series. Non
      native ethnic background was a predictor of completed vaccinations (odds ratio
      [OR] 5.40, 95% confidence interval [CI] 3.05 to 9.52). In a univariate model,
      urban area of residence was not a significant predictor of vaccination status,
      but when ethnic background was controlled for in a multivariate logistic
      regression analysis, urban area of residence was found to be inversely associated
      with completed vaccinations (OR 0.34, 95% CI 0.15 to 0.79). The number of days
      the child had spent in the NICU was not a significant predictor of vaccination
      status. CONCLUSION: The vaccination rate of infants discharged from the NICU is
      not optimal. Urban native children appears to be at risk of not being vaccinated.
      Non-native infants are five times more likely than native infants to have
      completed all of their scheduled vaccinations. Methods to improve the rate of
      completed vaccinations, especially for native children, must be sought and
      tested.

PMID- 7634217
TI  - Does the community want devolved authority? Results of deliberative polling in
      Ontario.
AB  - OBJECTIVE: To obtain and contrast the informed opinions of people in five
      decision-making groups that could have a role in devolved governance of health
      care and social services. DESIGN: Deliberative polling. SETTING: Three rural and
      three urban communities selected from the 32 areas covered by a district health
      council in Ontario. PARTICIPANTS: A total of 280 citizens from five potential
      decision-making groups: randomly selected citizens, attendees at town-hall
      meetings, appointees to district health councils, elected officials and experts
      in health care and social services. INTERVENTION: Participants' opinions were
      polled during 29 structured 2-hour meetings. MAIN OUTCOME MEASURES: Participants'
      opinions on their personal willingness and their group's suitability to be
      involved in devolved decision making, desired type of decision-making
      involvement, information preferences, preferred areas of decision-making
      involvement and preferred composition of decision-making bodies. RESULTS: Mean
      attendance at each meeting was 9.6 citizens. Although there were some significant
      differences in opinion among the five potential decision-making groups, there
      were few differences among citizens from different geographic areas. A total of
      189 (72%) of people polled were personally willing to take on a role involving
      responsibility for overall decision-making, but far fewer thought that their
      group was suited to taking on responsibility (30%) or a consulting role (55%).
      Elected officials were the most willing (85% personally willing, 50% thought
      their group was suitable) and randomly selected citizens the least willing (60%
      personally willing, 17% thought their group was suitable) to take responsibility
      for overall decision making. Most citizens polled indicated less interest in
      involvement in specific types of decisions, except for planning and setting
      priorities, than in overall decision making. Only 24 participants (9%) rated
      their own group as suitable to take responsibility for raising revenue, 91 (33%)
      deemed their group suited to distribution of funds and 108 (39%) felt their group
      was suitable for management of services. People in all five groups ranked health
      care needs (mean rank 1.5 out of four options) as the most important and
      preferences (mean rank 3.6) as the least important information. They rated a
      combination body involving several community groups as the most suitable overall
      decision-making body (8.8 on 10-point scale). Participants favoured the
      representation of elected officials, the provincial government and experts on
      combination bodies responsible for the specific types of decisions. Overall, as
      the complexity of devolved decision making became clear, participants tended to
      assign authority to traditional decision makers such as elected officials,
      experts and the provincial government, but also favoured a consulting role for
      attendees at town-hall meetings (i.e., interested citizens). CONCLUSION: There
      are significant differences among groups in the community in their willingness to
      be involved, desired roles and representation in devolved decision making on
      health care and social services in Ontario.

PMID- 7634219
TI  - Community participation in health care decision making: is it feasible?
AB  - Health care reform strategies proposed by provincial governments include
      decentralized funding and increased public participation in decision making.
      These proposals do not give details as to the public participation process, and a
      number of questions have been raised by the experience of some communities. Which
      citizens should form the decision-making group? What information do they need?
      What kinds of decisions should they make? What level of participation should they
      have? The results of a survey by Abelson and associates (see pages 403 to 412 of
      this issue) challenge the assumption that "communities" are willing to
      participate in health-care and social-service decision making. Willingness varied
      according to the composition of the groups polled, and participants' support for
      traditional decision makers increased after the complexities of the decision
      making process were discussed. However, whereas their study measured willingness
      to participate at one point in time only, experience gained from Ontario's Better
      Beginnings, Better Futures project indicates that, given sufficient time,
      "ordinary" citizens are willing and can acquire the skills needed to decide how
      resources should be allocated for social services.

PMID- 7634220
TI  - Harvesting blood proteins from grain.
AB  - A multidisciplinary team of researchers at the University of Ottawa has expressed
      a human blood protein, granulocyte-macrophage colony stimulating factor, in
      tobacco seeds as part of a series of experiments whose ultimate goal is to
      express human blood proteins in cereal crops. Success in these experiments may
      lead to the development of a new, relatively inexpensive and ready supply of
      these proteins from a biologic source that is generally recognized as safe. The
      team is also studying the possibility of expressing in seeds proteins that may be
      used as vaccines against infectious diseases.

PMID- 7634221
TI  - University acknowledges special risks, introduces drug program for anesthetists.
AB  - Anesthetists are at special risk for becoming addicted to some of the drugs they
      work with. The problem was highlighted by the recent death of a physician in
      Comox, BC, and a doctor's brush with death at a hospital near Ottawa. The
      University of Ottawa has responded with a program, the professional Assistance
      Program for the Impaired or Disabled Physician, that is in the final stages of
      approval. Although it will be aimed initially at anesthetists and anesthesia
      residents in the university's teaching hospitals, there are hopes the program
      will spread eventually to other medical departments.

PMID- 7634222
TI  - Canadian military physician one of many who tried to help Rwandans cope with a
      "world of hurt".
AB  - Lieutenant-Commander Colin Harwood was part of a team from the Canadian Forces
      Medical Service (CFMS) that was sent to Rwanda in the wake of that country's
      bloody civil war. The Ottawa-based officer says the CFMS personnel helped ease
      many serious medical problems during the 10 weeks they spent there, although the
      sheer numbers of wounded, diseased and orphaned people sometimes seemed
      overwhelming. The Canadian personnel helped more than 22,000 patients during
      their stay.

PMID- 7634223
TI  - A voice among the lemmings to the sea.

PMID- 7634225
TI  - Change: the rule rather than the exception.

PMID- 7634224
TI  - Community health CNSs and health care in the year 2000.
AB  - As our nation addresses health care reform and the need for programs at the
      community level that deal with preventable health problems, there is an
      increasing need for the community health clinical nurse specialist (CHCNS). In
      this article, the CHCNS's role, as defined by the profession, is discussed and
      ideas for implementing this role in the community, home health care and public
      health are proposed. Standards of Community Health Nursing Practice and Healthy
      People 2000 are resources the CHCNS can use to guide practice at the community
      level.

PMID- 7634226
TI  - The CNS in multidisciplinary pulmonary rehabilitation: a nursing science
      perspective.
AB  - Although nursing has been described as having an important role to play in the
      process of pulmonary rehabilitation, the extant literature on multidisciplinary
      pulmonary rehabilitation has not included a clear articulation of that role or
      its unique scientific base. The meaning of nursing science-based advanced
      practice to the team-oriented process of pulmonary rehabilitation is explored
      from the perspective of Parse's theory of human becoming. Philosophical notions
      informing practice from this perspective, as well as theory-based advanced
      nursing practice in pulmonary rehabilitation, are examined. CNS subroles of
      practice and research are discussed as essential avenues to development of this
      human science-based approach to advanced practice.

PMID- 7634227
TI  - The positive influence of animals: animal-assisted therapy in acute care.
AB  - Animal-assisted therapy is a therapeutic nursing intervention that brings animals
      together with persons with physical and/or emotional needs as a way of meeting
      those needs. It is based on the growing knowledge of benefits that animals
      provide to the sick, elderly, and isolated. A model for a responsible and outcome
      oriented program in animal-assisted therapy in acute care settings is described
      in this article. Special areas include: types of therapy, specific treatment
      goals, patient and animal suitability, environmental considerations, and
      evaluation methods.

PMID- 7634228
TI  - CNS research: variables of interest and reasons for being.

PMID- 7634229
TI  - Cost effectiveness: designing research for product evaluation.
AB  - The focus of this paper is planning of research to evaluate products or
      interventions used by nurses in the acute care setting. Research designs that can
      be used are presented with a discussion of problems encountered when implementing
      the designs in a hospital setting. Techniques to standardize care delivered to
      treatment and control groups are presented. Outcome measures, analytic
      techniques, and funding sources for this type of research are discussed.

PMID- 7634230
TI  - Help seeking in high risk pregnancy: the role of the CNS.
AB  - This study was designed to examine the type and amount of help sought from CNSs
      in a population of women who were experiencing a high risk pregnancy
      (specifically, gestational diabetes mellitus). The amount of subjective distress
      (perceived impact) experienced by the women was also explored as a predictor of
      help seeking behavior. Through the use of logs kept of each contact with
      subjects, episodes of help seeking were identified and classified. A total of 290
      episodes of help seeking were identified in the logs of 10 subjects representing
      199 contacts with subjects over 567 days of follow-up. The majority of help
      seeking episodes were classified as seeking knowledge (45.9%). Significant
      positive correlation was noted between the perceived impact of gestational
      diabetes mellitus and help seeking. Strong positive correlations were noted
      between help sought in the psychological, social, and economic categories and
      perceived impact. This data provide support for a CNS to care for this high risk
      population of women. Nurses in advanced practice have the ability to analyze
      clinical situations as well as to assess and address nonclinical variables that
      influence health.

PMID- 7634231
TI  - Responsible parenting: creating healthy families.

PMID- 7634232
TI  - Writing partnerships: a CNS and staff nurses write for publication.
AB  - Writing for publication with staff nurses can provide CNSs with flexible and
      creative approaches to the challenges facing nurses in the restructuring health
      care environment. CNSs experience many rewards and satisfactions from writing and
      measurable outcomes for practice evaluation. Staff nurses gain clinical
      knowledge, professional and career development, and the excitement that
      accompanies completion of a scholarly endeavor. Being in the clinical arena gives
      the CNS unique opportunities to work with and mentor staff nurses and observe
      their special capabilities, including those of a potential writing partner. How
      one CNS selected writing partners and supported these staff nurse colleagues
      through the writing-for-publication process is described in this article.

PMID- 7634233
TI  - Building healthy families: a program for single mothers.
AB  - With the ever-increasing number of single-parent families, innovative and
      creative strategies aimed to improve family health must be developed. The stress
      producing lifestyle of single-parent families offers great challenges to family
      CNSs. In this article, a project designed to teach positive health behaviors and
      life skills to female-headed single-parent families is described. The project,
      development and implementation of an education/support group, combines health
      education and small group discussion for an effective therapeutic intervention
      for single-parent female participants.

PMID- 7634234
TI  - Adult nurse practitioner/clinical nurse specialist: roles in health care reform.

PMID- 7634235
TI  - The new frontier in community health nursing.

PMID- 7634236
TI  - Inside looking out: innovations in community health nursing.
AB  - The Portland Veterans Affairs Medical Center provides a range of health care
      services for an aging population. The chronic, multiple health problems of
      veterans and the complexity of the health care delivery system often lead to
      fragmented and discontinuous care. The innovative model of advanced practice
      nursing described here involves using hospital-based community health CNSs in the
      role of community health coordinators. The three CNSs described here each have
      unique and overlapping responsibilities. Based primarily in the medical center,
      they are able to facilitate a smooth patient transition from the hospital to the
      community using knowledge and experience to assess, plan, implement, and evaluate
      care needs of three defined populations. In this article, responsibilities of the
      community health CNS are defined and the Portland VA Medical Center and
      population served are described. The history of the community health coordinator
      role is outlined, followed by the current role description and targeted
      populations, and role impacts to date.

PMID- 7634237
TI  - A perfect clinical example.

PMID- 7634238
TI  - Nursing consultation to reduce restraints in a nursing home.
AB  - Consultation is an important function of advanced practice nurses. Within nursing
      practice, the process of providing consultation has been studied primarily in
      acute care settings. A CNS in a 180-bed, nonprofit nursing home implemented the
      intervention for a controlled clinical trial of nursing interventions to reduce
      physical restraint use. The consulting process undertaken by the CNS is
      described, and conclusions are offered regarding the most effective approaches to
      consultation by advanced practice nurses in nursing homes.

PMID- 7634239
TI  - Chromophore-enhanced in vivo tumor cell destruction using an 808-nm diode laser.
AB  - Rat mammary tumors were treated using an 808-nm diode laser in a power range of 3
      15 W. Photothermolysis was selectively enhanced by the chromophore indocyanine
      green (ICG), which has an absorption peak corresponding to the laser wavelength.
      ICG, injected into neoplastic tissues 24 h before laser exposure, was retained in
      sufficient quantity to produce a strong photothermal reaction. With appropriate
      laser power and adequate irradiation duration, laser energy could inflict severe
      photothermal damage to the entire targeted tumor tissue while leaving the skin
      and other interdicted tissue undamaged. Higher laser powers (10-15 W) produced
      more surface damage that limited light transmission and as a result gave rise to
      reduced regions of thermal destruction. Post-treatment observation revealed the
      survival of numerous tumor cells. This finding questions the long term efficacy
      of the photothermal effect of a single treatment using the combination of the ICG
      and the diode laser, particularly in the absence of other modalities.

PMID- 7634240
TI  - P-glycoprotein expression by human colonic tumor cells influences the growth of
      tumor cells in vitro.
AB  - The stability of P-glycoprotein expression by high and low expressing cells
      obtained by flow sorting from two cell lines established from colonic tumors was
      assessed. Low expressing cells rapidly recovered expression to a level that was
      comparable to that determined for uncloned cells. High expressing cells
      maintained a high level of expression relative to the parental uncloned lines,
      although there was continuous reversion to a level of expression determined for
      the parental line with time. The population growth rates for high expressing
      cells was greater than that of parental and low expressing cells when assessed
      immediately following plating of sorted cells. The data suggest that high
      expression of P-glycoprotein confers a growth advantage which may increase
      repopulation and dissemination of tumor cells following drug therapy.

PMID- 7634241
TI  - Inhibitory effects of quassinoids on Epstein-Barr virus activation.
AB  - Short-term in vitro assays for tumor promoters and anti-tumor promoters (Epstein
      Barr virus activation test) were carried out for 45 quassinoids. As a result,
      some quassinoids showed potent activity, more than 50% inhibition at a molar
      ratio of 1:1 (TPA/quassinoids). These results led to the following structure
      activity relationships: (1) a methyleneoxy bridge and side chain enhance the
      activity and (2) a sugar moiety reduces the activity.

PMID- 7634242
TI  - Local application of gamma-linolenic acid in the treatment of human gliomas.
AB  - gamma-Linolenic acid (GLA) has been shown to have selective tumoricidal action
      both in vitro and in vivo. Earlier, in a limited clinical study, we have
      demonstrated that intra-tumoral administration of GLA can induce regression of
      human gliomas. In an extension of this study, we evaluated the effect of intra
      cerebral injection of GLA on normal dog brain and in 15 patients with malignant
      gliomas. Histopathological examination revealed that GLA is not cytotoxic to the
      normal dog brain cells. Administration of 10 mg of GLA via a cerebral reservoir
      placed in the tumour bed, at the rate of 1 mg/day over a period of 10 days,
      revealed that GLA is not only safe and non-toxic but can also regress cerebral
      gliomas as evaluated by computerised tomography and increased survival of the
      patients by 1.5-2 years. Based on these results and our earlier in vitro study,
      we suggest that GLA is a safe anti-tumour agent and recommend its use in the
      management of human gliomas.

PMID- 7634243
TI  - Insulin-like growth factor-I is an autocrine regulator for the brain metastatic
      variant of a human non-small cell lung cell line.
AB  - Insulin-like growth factor (IGF-I) is associated with autocrine and paracrine
      stimulation for cell growth and development of brain tumor cells. The function of
      IGF-I in the brain metastatic variant of human lung cancer cells is investigated.
      The cells used here were derived in vivo with intracarotid injection of human non
      small cell lung carcinoma NCI-H226. The tumor was developed as a cultured cell
      line, H226Br. Unlike the parental cells, H226Br was tumorigenic in nu/nu nude
      mice. Reverse transcriptase-polymerase chain reaction showed that IGF-I
      transcript of H226Br is increased compared to that of parental cells. The amount
      of IGF-I secreted in cultured medium of H226Br is higher than that of cultured
      parental cells. The IGF-I receptor-specific antibody, alpha IR3, inhibits H226Br
      growth in serum-free culture. The results established that IGF-I is an autocrine
      growth regulator for human non-small cell lung cancer cells that progressed to
      brain.

PMID- 7634244
TI  - Neoplastic alterations in subcellular distribution of type 1 alpha protein
      phosphatase in rat ascites hepatoma cells.
AB  - Neoplastic alterations of type 1 alpha protein phosphatase (PP1 alpha) have been
      studied in rat ascites hepatoma cells, using regenerating liver after partial
      hepatectomy and normal rat liver as controls. In the particulate fraction of
      hepatomas, potential PP1 activity and the amount of PP1 alpha were remarkably
      increased compared with either regenerating or normal livers. In the nuclear
      fraction, PP1 activity and the amount of PP1 alpha were increased in hepatoma
      compared with the controls. The nuclear PP1 activity in hepatomas was activated
      by treatment with CO2+/trypsin, whereas that of normal or regenerating liver was
      not activated. These characteristic alterations of PP1 alpha in its amount and
      subcellular distribution may be implicated in malignant phenotype(s) such as
      uncontrolled cell growth.

PMID- 7634245
TI  - Effects of an antibiotic protease inhibitor, actinonin on the growth within
      collagen gels of non-metastatic and metastatic mouse mammary tumors of the same
      origin.
AB  - Of five autonomous sublines established independently from the transplantable
      hormone-dependent mouse mammary tumor, TPDMT-4, three but not two acquired
      metastatic potential. In in vitro culture using collagen gels, actinonin, an
      antibiotic protease inhibitor exerted a stronger growth-inhibiting effect on the
      metastatic than on the parent and non-metastatic tumors. Zymographic analysis
      demonstrated the active forms of gelatinases in the metastatic but not in the non
      metastatic sublines and the complete inhibition of the enzyme activities by
      actinonin. Gelatinases/type IV collagenases might play an important role in tumor
      progression towards metastatic phenotype and actinonin may suppress tumor growth
      through inhibiting collagenase.

PMID- 7634246
TI  - Effects of dietary fish oil (MaxEPA) on N-nitrosobis(2-oxopropyl)amine (BOP)
      induced pancreatic carcinogenesis in hamsters.
AB  - In the present study the chemopreventive potential of 25% fat (HF) diets
      containing 2 wt% linoleic acid (LA) and including 0.0, 1.2, 2.4, 4.7, 7.1 or 9.4
      wt% dietary fish oil (MaxEPA) has been investigated using the N-nitrosobis(2
      oxopropyl)amine (BOP)-hamster model for pancreatic cancer. The number of
      pancreatic borderline lesions (BLL) was significantly higher (P < 0.05) in the HF
      groups containing 1.2, 2.4 or 9.4 wt% MaxEPA in comparison with the HF group
      without MaxEPA. MaxEPA inhibited the metabolism of LA to arachidonic acid (AA)
      and of AA to prostaglandins (PGs) in both blood plasma and pancreatic microsomes.
      The pancreatic levels of PGE2 (P < 0.05), 6-keto-PGF1 alpha (P < 0.01) and PGF2
      alpha (P < 0.05) decreased significantly with increasing dietary MaxEPA. The
      levels of PGE2 (P < 0.001), 6-keto-PGF1 alpha (P < 0.05), PGF2 alpha (P < 0.001)
      and thromboxane (TX) B2 (P < 0.001) in pancreatic adenocarcinomas were higher
      than in non-tumorous pancreas. The MaxEPA had no significant effect on the BrdU
      labeling index (LI) in acinar, ductular or centroacinar cells, nor on the LI in
      BOP-induced pancreatic lesions. It is concluded that (i) dietary fish oil has a
      slight enhancing effect on BOP-induced pancreatic carcinogenesis in hamsters and
      (ii) dietary fish oil dose-dependently inhibits the conversion of LA to AA and of
      AA to certain PGs and (iii) dietary fish oil does not influence the cell
      proliferation in hamster pancreas.

PMID- 7634247
TI  - Interferon-alpha-induced protection of renal cell cancer cell line from lysis by
      natural killer cells and increase of susceptibility by treatment with 5
      fluorouracil.
AB  - We have shown previously that interferon (IFN)-alpha reduces the sensitivity of
      renal cell cancer (RCC) cell lines ACHN and KRC/Y to lysis by lymphokine
      activated killer (LAK) cells. The close relationship between natural killer (NK)
      cells and LAK cells prompted us to investigate whether IFN-alpha pretreatment
      also affects the sensitivity of ACHN cells to lysis by NK cells or IFN-alpha
      activated NK cells. A 51Cr-release cytotoxicity assay demonstrated that
      pretreatment of ACHN with IFN-alpha decreased their susceptibility to NK cells
      and IFN-alpha-activated NK cells in a dose-dependent manner. Moreover, to
      investigate the usefulness of 5-fluorouracil (5FU) for combination with IFN-alpha
      therapy, we examined the effect of preincubation with 5FU on the susceptibility
      of ACHN. IFN-alpha-induced protection of ACHN from lysis by IFN-alpha-activated
      NK cells weakened in the presence of 5FU at 0.2 microgram/ml. An adhesion assay
      showed that preincubation of ACHN with 5FU and IFN-alpha did not alter the
      adhesion of IFN-alpha-activated NK cells. A cold target competition analysis did
      not show any difference between untreated and 5FU and/or IFN-alpha-treated
      competitors. These results suggest that one of the mechanisms of 5FU for
      combination with IFN-alpha therapy might depend on changes of RCC cells in
      intrinsic lysability involving a post-binding stage of the lytic cycle to NK
      cells.

PMID- 7634248
TI  - Effects of Viscum album L. on cyclophosphamide-treated peripheral blood
      mononuclear cells in vitro: sister chromatid exchanges and
      activation/proliferation marker expression.
AB  - Based on recently published data, Viscum album L. (VAL) extracts have been shown
      to provide a DNA stabilizing effect which seems to be restricted to the
      peripheral blood mononuclear cells (PBMC). We have now investigated whether VAL
      exerts effects of cellular protection for phytohemagglutinin-activated PBMC
      treated with cyclophosphamdie (CP) in vitro. The addition of VAL resulted in a
      slight reduction of CP-induced sister chromatid exchanges of cultured PBMC from
      healthy individuals. The incubation with CP significantly reduced the expression
      of the low affinity interleukin-2 receptor (IL-2R alpha chain) and of transferrin
      receptor (TfR) on PHA-stimulated T lymphocytes. The addition of 10 micrograms/ml
      VAL was protective against the CP-induced depression of IL-2R alpha chain and TfR
      expression on these cells. The simultaneous addition of CP and purified VAL
      components, such as ML I, ML II/III, and viscotoxins did not significantly change
      expression of IL-2R alpha chain and TfR on T cells. Thus, so far undefined VAL
      components might be responsible for the observed protection effects of the whole
      plant extract. The results presented here should encourage investigation of this
      drug, which might become an interesting adjuvant in cancer therapy.

PMID- 7634249
TI  - Serum concentrations of 5-fluorouracil achieved with nocturnal constant-rate
      infusion in patients with disseminated cancer.
AB  - Nocturnal infusion of 5-fluorouracil (FUra) was performed in nine patients with
      disseminated cancer. Three gastric, three colon and three breast cancer patients
      were administered 300 mg/m2 FUra continuously for 10 h per day from 2100 h to
      0700 h for more than 20 consecutive days. In the first three patients, who were
      treated by drip infusion without the use of a volumetric pump, serum FUra
      concentrations ranged widely, from 27 to 130 ng/ml, even though the rate of
      administration was re-adjusted four times during the night. The last six patients
      were treated using a volumetric pump, and FUra concentrations in serum ranged
      from 175 to 378 ng/ml, and displayed no circadian rhythm. Although the dose
      intensity and area under the curve of FUra in these patients were high, neither
      myelosuppression nor other side effects were observed.

PMID- 7634251
TI  - 8-Hydroxydeoxyguanosine levels in DNA of human breast cancers are not
      significantly different from those of non-cancerous breast tissues by the HPLC
      ECD method. Cancer Letters 90, 157-162.

PMID- 7634250
TI  - Serum evaluation of basic fibroblast growth factor in cervical cancer patients.
AB  - We present the data of 105 serum samples from 20 patients suffering from cervical
      cancer. Mean serum levels of basic fibroblast growth factor (bFGF) in patients
      with or without tumor present were 31.3 +/- 32.1 (minimum 0, maximum 156.7) pg/ml
      and 4.8 +/- 6.8 (minimum 0, maximum 29.6) pg/ml, respectively (P = 0.0001). bFGF
      reached a sensitivity of 65.7% at a specificity of 91.5% when applying a cut-off
      level of 15 pg/ml. Four patients relapsed after complete remission. A continuous
      increase of bFGF serum levels before the clinical detection of relapse (lead
      time) was seen in two cases with a mean lead time of 4 months. Preoperative serum
      levels were not of prognostic value and showed no correlation with pelvic lymph
      node metastasis. These preliminary results indicate that in cervical cancer
      patients soluble bFGF may be useful in early detection of primary tumors,
      recurrences and monitoring of therapy.

PMID- 7634252
TI  - [Role of transesophageal echocardiography in aortic dissection].
AB  - Aortic dissection, especially type A, is a life-threatening condition, that
      requires a prompt and accurate diagnosis to ensure a rapid and precise
      therapeutic approach. Transesophageal echocardiography (TEE) is a highly reliable
      technique because of its sensitivity and specificity (near 100%; almost similar
      to nuclear magnetic resonance), and because it is a very low risk, rapid and easy
      diagnostic tool. Two hundred sixty-one patients were admitted at our institution
      in a 6-year period (1988-1994), because of a suspicion of aortic dissection. Two
      hundred forty-seven of them were submitted to TEE and the diagnosis was compared
      with surgical data in 124. There was only one false positive by TEE. Sensitivity
      of TEE vs surgery was 100%, specificity 93.7%, diagnostic accuracy 99%. Agreement
      between TEE and surgery in the setting of intimal tear was 69.2%. These data
      confirm the usefulness of TEE in the diagnostic approach to aortic dissection and
      the therapeutic decision, without using other methods.

PMID- 7634253
TI  - [Assessment of viable myocardium after infarction with transesophageal
      echocardiography and myocardial echocontrastography].
AB  - Left ventricular recovery of dysfunctioning but viable myocardium can occur only
      in tissue in which both myocardial contractile reserve and microvascular
      integrity are preserved. Recent studies have demonstrated that both inotropic
      stimulating echo tests and myocardial contrast echocardiography can be used to
      assess myocardial viability in post-myocardial infarction patients. Therefore we
      performed a transesophageal and myocardial contrast echocardiographic evaluation
      of post-myocardial infarction patients to assess: the respective accuracy of post
      extrasystolic potentiation and low-dose dobutamine (5 and 10 mcg) during
      transesophageal echocardiography in eliciting contractile reserve, and the
      potential of myocardial contrast echocardiography in predicting later functional
      recovery. Results of our studies showed comparable effects of low-dose dobutamine
      (5 mcg) and post-extrasystolic potentiation in increasing myocardial thickening
      while low-dose dobutamine (10 mcg) had a greater potential in eliciting residual
      contractility. Lastly, myocardial contrast echocardiography provided a clear
      spectrum of intramyocardial perfusion patterns in dysfunctioning areas but did
      not accurately correlate with later functional recovery as better predicted by
      low-dose dobutamine in the same segments. In conclusion, these methods represent
      the preferred choice of studying the perfusion-contraction match in viable
      myocardium thus playing an important role in prognostic and therapeutic
      strategies in myocardial infarction patients.

PMID- 7634254
TI  - [Transesophageal stress echocardiography].
AB  - The Authors analyze the literature data on transesophageal stress
      echocardiography and personal experience with dipyridamole echocardiography.
      Advantages and limitations for the clinical application of this method are
      discussed taking into account computer-aided echocardiographic images.
      Transesophageal stress echocardiographic results are compared with those obtained
      by other stress test imaging techniques.

PMID- 7634255
TI  - [The cardiac tissue renin-angiotensin system].
AB  - In the last years molecular biological studies proved the presence of mRNA for
      the various components of the renin-angiotensin system (RAS) in animal and, more
      recently, in human myocytes. Moreover, higher mRNA levels for the various
      components of cardiac RAS were demonstrated in different experimental conditions
      such as myocardial hypertrophy, infarction and heart failure. These experimental
      evidences suggest the existence of a cardiac RAS, even if up to now direct
      evidence is lacking of a cardiac functioning RAS autonomous from the plasmatic
      system.

PMID- 7634256
TI  - [ACE-inhibitors and water metabolism in heart failure].
AB  - At least theoretically, ACE-inhibitors may influence each of the factors involved
      in the regulation of salt and water metabolism. Angiotensin II exerts an
      antidiuretic and antinatriuretic action on the kidney through influences on the
      glomerular filtration coefficient, glomerular filtration rate, mesangial tone,
      filtration fraction, proximal and distal tubule. Angiotensin II and renin also
      regulate the input of water and salt through an unequivocal dipsogenic effect. In
      congestive heart failure angiotensin II participates in the preservation of the
      glomerular filtration rate through its vasoconstrictor properties on the systemic
      vessels (maintenance of the perfusion and filtration pressure) as well as on the
      efferent arteriole (maintenance of the filtration pressure). ACE-inhibition
      weakens or abolishes these influences. However, two favorable mechanisms may also
      come into action: rise of cardiac output and improvement in renal blood flow;
      widening of the filtration surface and increment of the filtration coefficient.
      The efficacy of these factors depends on renal function, age, functional recovery
      of the heart, treatment with diuretics, duration of treatment with ACE
      inhibitors, duration of action of the ACe-inhibitor used, blockade of the
      facilitating action on the adrenergic vasoconstriction, formation of vasodilating
      prostaglandins, reduced degradation of kinins. All these effects may account for
      the variable and often contradictory clinical results, in particular as concerns
      the relationship between ACE-inhibition and use of diuretics in congestive heart
      failure. This also explains the variability of efficacy (from the development of
      pulmonary edema and requirement of diuretics to diuretic withdrawal and clinical
      improvement) of the ACE-inhibitors as monotherapy in mild to moderate heart
      failure.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7634257
TI  - [ACE-inhibitors and cardiovascular protection].
AB  - Aim of recent experimental and clinical studies has been to evaluate the
      important role of the renin-angiotensin system in the development of cardiac
      hypertrophy, of vascular hypertrophy and of left ventricular fibrosis and
      remodelling in essential hypertension and ischemic heart disease. It has been
      suggested that ACE-inhibitors are the class of antihypertensive drugs more
      effective in reducing left ventricular hypertrophy (LVH) in hypertensive
      patients. The possible mechanisms are, beyond the decrease in blood pressure, the
      possibility of interfering not only with the renin-angiotensin system activity,
      but also with the sympathetic nervous system activity as well as with aortic
      distensibility, all factors that can influence the development of LVH. Vascular
      changes in essential hypertension are complex and depend not only on the severity
      of blood pressure levels, but are related to diameter and structure of the
      vessels and to the presence of other atherosclerosis risk factors. ACE-inhibitors
      are effective in inducing the regression of structural changes in resistance
      arterioles and furthermore can increase arterial compliance in large arteries;
      new studies are undergoing in order to assess the effects of these drugs on
      atherosclerotic plaque progression/regression. The results of large clinical
      trials have shown the efficacy of ACE-inhibitors in the treatment of heart
      failure, in addition, after it has been demonstrated that ACE-inhibitors can
      influence the structural remodelling process after myocardial infarction, their
      use has been extended to patients with ischaemic heart disease.

PMID- 7634258
TI  - [Trials with ACE-inhibitors in acute myocardial infarction].
AB  - In acute myocardial infarction, the results of the trials with ACE-inhibitors
      have not been always good, in contrast with what has been observed in chronic
      heart failure. The comparison of these compounds with the placebo has
      demonstrated lack of reduction of mortality in the study CONSENSUS II, favorable
      results on the survival as first endpoint and on the secondary endpoints, as
      reinfarction, heart failure and stroke in the studies SOLVD, AIRE, GISSI 3, ISIS
      4, and uncertain (interim report) results in the Chinese study. Nevertheless, the
      analysis of the recruitment of the patients with acute infarction and the way
      these patients have been treated seem to be the most important cause of the
      conflicting results. ACE-inhibitors have proved no efficacy in acute myocardial
      infarction without signs of left ventricular failure (CONSENSUS II), have
      worsened the clinical picture and the mortality in patients in shock or with
      severe heart failure in the acute phase. On the reverse, in presence of mild to
      moderate left ventricular dysfunction and failure, the use of ACE-inhibitors has
      been followed by reduction of mortality in the early (AIRE, GISSI 3, ISIS 4),
      medium term (GISSI 3) and long-term follow-up (up to 4 years in the AIRE study).
      In parallel with the reduction of the primary endpoint, also secondary endpoints
      have been favorably influenced by the different ACE-inhibitors. No differences
      have been observed among the different class of compounds. ACE-inhibitors seem,
      therefore, to have a clear indication in acute myocardial infarction with mild or
      moderate signs and symptoms of heart failure.

PMID- 7634259
TI  - [Low-dose aspirin in the long-term treatment of the patient with ischemic heart
      disease].
AB  - Coronary atherosclerosis is the process underlying virtually all the clinical
      manifestations of ischemic heart disease. When ulcer or fissure in the fibrous
      cap of the atheroma occur, platelet adhesion to subendothelium, aggregation and
      further platelet recruitment culminate in thrombus formation. These mechanisms
      are known to be responsible for most cases of acute events in patients with
      ischemic heart disease. Inside platelets, aspirin blocks the synthesis of
      thromboxane A2 by irreversibly inhibiting cyclooxygenase. Aspirin is recommended
      not only for treatment of patients with acute coronary syndromes (unstable
      angina, acute myocardial infarction), but also for secondary prevention of
      vascular events in chronic coronary syndromes. Aspirin prevents myocardial
      infarction in patients with chronic stable angina and reduces mortality,
      reinfarction and stroke in survivors of an acute myocardial infarction. Aspirin,
      alone or in combination with dipyridamole, prevents early and late occlusion of
      aortocoronary vein grafts. It is useful also in patients undergoing coronary
      angioplasty. Such benefits extend to all patients regardless of age, sex, history
      of hypertension or diabetes. Higher daily doses (900-1500 mg) are not more
      effective than lower doses (75-325 mg). Other antiplatelet drugs are not more
      effective than aspirin, which has the best risk-to-benefit and cost-to-benefit
      ratios. Ticlopidine is a reasonable alternative for use in preventing vascular
      events among patients intolerant to aspirin. Warfarin is an effective
      antithrombotic alternative to aspirin for secondary prevention after a myocardial
      infarction. However aspirin is easier to administer and follow-up when compared
      with warfarin. Warfarin should be preferred in high risk patients with left
      ventricular dysfunction with or without a mural thrombus, and those with
      associated atrial fibrillation.

PMID- 7634260
TI  - [Microalbuminuria, hypertension, and cardiovascular risk].
AB  - A growing interest in the study of microalbuminuria (Mi) in essential
      hypertension (EH) has recently emerged. While clinical proteinuria is found with
      a low frequence (between 4 and 16%) in patients with EH, a variable but generally
      higher prevalence (10-40%) of Mi has been reported, even in the absence of
      diabetes and nephropathy. Mi is defined as an abnormal urinary excretion of
      albumin (20-200 micrograms/min), undetectable by conventional tests. Variations
      in the prevalence of Mi in different studies may be attributed to different
      selection criteria, techniques for detection of albuminuria, the severity of
      hypertension, age, race, coexistence of renal disease as well as the number of
      patients studied and the presence or absence of antihypertensive treatment. It is
      unknown whether the predictive value of albuminuria reflects its association with
      more severe hypertension and target organ damage, or whether albuminuria serves
      as an indicator of capillary leakiness which causes detectable abnormalities in
      the renal microcirculation but reflects more generalized endothelial barrier
      dysfunction predisposing to accelerated atherogenesis. Mi has been associated
      with higher blood pressure levels, a worse lipid profile as well as the presence
      of target organ damage, namely peripheral artery disease and left ventricular
      hypertrophy in patients with EH. Several studies have shown a correlation between
      Mi and/or proteinuria and cardiovascular diseases independently of other risk
      factors and cardiovascular mortality to be ten times higher in patients with Mi
      than in normoalbuminuric patients. Long-term prospective studies are needed in
      order to clarify the exact prevalence of Mi, its predictive value for the
      development of clinical proteinuria and renal function deterioration as well as
      the effect of different antihypertensive drugs.

PMID- 7634261
TI  - [Hyperinsulinemia and cardiovascular risk].
AB  - A large body of evidence has been accumulating that insulin plays a role in
      coronary heart disease (CHD). Hyperinsulinemia has been considered a risk factor
      for CHD according to prospective studies. Cross-sectional studies found an
      association between hyperinsulinemia and prevalence of CHD, while population
      studies have shown that populations at increased risk for CHD are
      hyperinsulinemic. Strong relations between hyperinsulinemia and atherosclerotic
      coronary lesions have been demonstrated by angiographic studies. It has recently
      been observed that also patients with microvascular angina are hyperinsulinemic.
      Several mechanisms have been proposed to explain the role of hyperinsulinemia in
      the development of atherothrombosis. Hyperinsulinemia is the consequence of
      insulin resistance, a defect in insulin-mediated glucose uptake. Experimental
      evidence suggests that insulin has actions that may promote atherosclerosis,
      which clinical studies suggest the existence of a metabolic syndrome
      characterized by the presence of major coronary risk factors in which insulin
      resistance is the common link.

PMID- 7634262
TI  - Lipids and plasma fibrinogen: early and late composition of the atherosclerotic
      plaque.
AB  - Raised levels of plasma low density lipoprotein, lipoprotein (a), and fibrinogen
      have emerged as major risk factors for myocardial infarction and atherosclerosis.
      In this brief review some of their interactions with arterial intima are
      discussed. All the plasma macro-molecules appear to be present even in normal
      intima, and to cross the endothelium in healthy, young experimental animals by
      vesicular transport. The precursor of large fibrous plaques appears to be the
      gelatinous lesion, which is characterized by oedema, accumulation of large
      amounts of low density lipoproteins and fibrinogen in the expanded interstitial
      fluid space, deposition of fibrin, and smooth muscle cell proliferation. It is
      postulated that deposition of fibrin may be a key event, stimulating smooth
      muscle cell proliferation by providing a scaffold for migration, a source of
      fibrin degradation products which are mitogenic, and binding thrombin. Fibrin may
      also be a factor in lipid accumulation because it binds lipoprotein (a) with high
      affinity, and may also bind low density lipoprotein.

PMID- 7634263
TI  - [Interactions between atherosclerosis and ischemic stimuli in the pathogenesis of
      acute coronary syndromes].
AB  - Until a few years ago coronary atherosclerosis was thought to be a slowly
      progressive disease eventually leading to total coronary occlusion and myocardial
      infarction. Recent angiographic studies have shown, instead, that mild or
      moderate coronary stenoses have the highest risk of causing acute coronary
      syndromes when complicated by thrombus formation which, in turn, appears to be
      due to a complex interaction between the atherosclerotic background and acute
      ischemic stimuli. The tendency of the atherosclerotic background to develop
      thrombosis may be different in different patients, as indicated by the
      observation that the risk factor profile of patients who present with chronic
      coronary syndromes is different from that of patients who present with acute
      syndromes. The acute ischemic stimuli so far identified are: a sudden local
      thrombogenic stimulus; a transient systemic increase in systemic pro-coagulant
      activity; a transient increase in proximal and/or distal coronary tone. The
      recent observation of inflammatory cells activation, including T-lymphocytes, in
      patients with acute ischemic syndromes raises the intriguing possibility that a
      specific antigenic stimulus may play an important pathogenetic role.

PMID- 7634264
TI  - [Elements conditioning the severity of myocardial infarction damage].
AB  - The severity of myocardial damage following acute myocardial infarction (AMI) is
      essentially influenced by the duration of coronary flow interruption during the
      acute episode. Furthermore the duration and severity of "culprit" lesion before
      AMI, as well as the presence of adequate collaterals to the culprit vessel
      represent important factors able to influence the severity of myocardial
      dysfunction after AMI. Left ventricular damage might evolve progressively
      depending on the infarct size, the presence of diffuse and severe coronary artery
      disease and concomitant systemic disease, such as diabetes and systemic
      hypertension. From a therapeutic point of view, in the presence of irreversible
      myocardial damage (scar tissue) following AMI medical therapy must be addressed
      to reduce myocardial consumption and to prevent ventricular dilatation. However
      myocardial dysfunction following AMI might be reversible (hibernated myocardium).
      It is of remarkable value the recognition of the hibernated but viable tissue
      because restoration of normal blood flow, which is the gold standard therapy in
      these patients, improves myocardial function and clinical outcome in AMI
      patients. In the presence of hibernated tissue following AMI, pharmacological
      therapy might temporarily protect the hibernated areas; however, when restoration
      of normal blood flow (myocardial revascularization) is not performed early,
      myocardial dysfunction might worsen and progressively evolve becoming
      irreversible event with restoration of normal coronary flow.

PMID- 7634265
TI  - [Myocardial viability in acute myocardial infarction and verapamil].
AB  - Following prolonged ischemia, if not adequately reperfused, myocardium undergoes
      necrosis, scarring and thinning. The myocardium tends to dilate in the
      noninfarcted ventricular area, giving rise to ventricular remodelling. If the
      ischemic myocardium is adequately reperfused it can be saved and its temporarily
      depressed functions eventually be recuperated (viable myocardium). The extent of
      recovery of the postinfarction viable myocardium seems to affect ventricular
      remodelling. The integrity of the microcirculation of the non-contractile
      myocardium following prolonged ischemia is fundamental in maintaining a
      contractile reserve adequate enough for a functional recovery (myocardial
      viability). Protection of the microcirculation during ischemia-reperfusion is
      therefore of great importance for the role that the microcirculation plays in
      ensuring myocardial viability. Experimental studies and initial clinical
      observations showed that calcium-antagonists exert a beneficial effect in this
      respect. VAMI is a multicentre, randomized double-blind, placebo-controlled study
      whose aim is to ascertain the potentiality of verapamil in limiting regional
      functional damage in patients with acute myocardial infarction and undergoing
      early thrombolysis.

PMID- 7634267
TI  - [Microcirculation and remodelling].
AB  - Acute myocardial infarction can produce alterations in the topography of the left
      ventricle both in the infarcted and remote areas. These changes as a whole, have
      been termed ventricular remodelling. Attention has been focused on myocyte
      alterations due to the remodelling process, but the myocardial wall also contains
      fibroblasts, which produce collagen and elastin fibers, and endothelial and
      smooth muscle cells which are the main constituents of the vascular wall. In left
      ventricular hypertrophy, a form of myocardial remodelling, structural changes of
      myocytes, cardiac interstitium as well as the coronary microcirculation have been
      found (vascular remodelling). In vivo, the function of coronary microcirculation
      can be evaluated by measuring myocardial blood flow and coronary reserve. In fact
      the study of coronary reserve in patients with left ventricular hypertrophy
      disclosed microcirculatory dysfunction which probably represents the functional
      counterpart of the structural changes already described. Positron emission
      tomography (PET) can noninvasively quantitate myocardial blood flow and coronary
      reserve in humans. Recently studies with PET disclosed microcirculatory
      alterations also in patients with coronary artery disease (CAD) in the absence of
      gross myocardial hypertrophy. In particular, after myocardial infarction,
      coronary vasodilator capacity has been shown to be impaired not only in the
      infarcted areas but also in the remote ones subtended by angiographically normal
      vessels. A blunted coronary reserve has been identified with PET also in remote
      regions from ischemia in patients with stable angina and single vessel CAD.

PMID- 7634266
TI  - [ACE-inhibitors after infarction: current knowledge and future prospects].
AB  - Experimental and clinical findings showing a beneficial effect on ventricular
      remodelling have led to a widespread use of ACE-inhibitors in myocardial
      infarction. Recent trials (SAVE, AIRE, GISSI 3, ISIS 4) have clearly demonstrated
      that in patients with left ventricular dysfunction and/or heart failure the
      treatment with ACE-inhibitors is mandatory, although several questions remain
      unanswered. Recent experimental observations on the relationship between ACE and
      endothelial function, and between ACE and intimal proliferation have gone forward
      leading to new perspectives on the potential use of ACE-inhibitors in all
      patients with acute myocardial infarction.

PMID- 7634269
TI  - [Methods for assessing the autonomic nervous system in man].
AB  - Assessment of baroreflex sensitivity and spectral analysis of heart rate
      variability are two methods capable of providing relevant information on neural
      mechanisms controlling heart period and on their alterations during several
      pathophysiological conditions such as coronary artery disease and cardiac
      insufficiency. These techniques provide complementary information: the former is
      based on a stimulus-response model which has in the activation of vagal fibers
      directed to the heart its main efferent component; the latter, by quantifying the
      spontaneous harmonic oscillations of heart period, furnishes indices of
      sympathetic and vagal modulation of sinus node.

PMID- 7634270
TI  - [Acute ischemia, autonomic reflexes, and ventricular fibrillation].
AB  - The effects of the autonomic nervous system on malignant arrhythmias,
      particularly in the setting of ischemic heart disease, have been widely
      investigated and described. Specifically, while sympathetic hyperactivity is
      arrhythmogenic, an increased vagal activity often exerts a beneficial effect. New
      insights on the relationship between autonomic activity and sudden cardiac death
      have been obtained in conscious dogs in which a healed myocardial infarction,
      acute myocardial ischemia and exercise are combined. In this chronic animal model
      myocardial infarction reduces baroreflex sensitivity and heart rate variability
      (markers of vagal reflex and tonic activity to the heart) and a depressed
      baroreflex sensitivity or a reduced heart rate variability after myocardial
      infarction indicates an increased risk for ventricular fibrillation. The clinical
      relevance of these experimental observations was confirmed in studies in patients
      with myocardial infarction. Exercise training increases vagal control of heart
      rate and concomitantly prevents recurrence of ventricular fibrillation during
      acute ischemia in dogs susceptible to sudden death. The protective effect of
      vagal activity is further confirmed by the experimental evidence that electrical
      stimulation of the vagus is able to prevent ventricular fibrillation during acute
      myocardial ischemia. The possibility of modulating the autonomic control of
      cardiac activity by means of pharmacologic and non pharmacologic interventions
      able to increase cardiac vagal activity represents a rational and promising
      approach to reduce risk for lethal events after myocardial infarction.

PMID- 7634268
TI  - [Evolution of myocardial ischemia therapy: calcium antagonists and ACE
      inhibitors].
AB  - We have considered the possibility that the association between Ca(2+)
      antagonists and ACE-inhibitors may be useful to treat patients with myocardial
      infarction. The two classes of drugs have synergic and complementary effects in
      terms of mechanism and site of action and of cardioprotective properties. In
      clinical trials Ca(2+)-antagonists failed to improve prognosis of patients with
      myocardial infarction, except verapamil which reduces mortality in patients with
      myocardial infarction and without pulmonary congestion. ACE-inhibitors are
      effective only in patients with myocardial infarction and congestive heart
      failure. Thus the two classes of drugs could be useful to treat patients with
      myocardial infarction but this hypothesis has to be confirmed with properly
      designed clinical trials.

PMID- 7634271
TI  - [Assessment of the autonomic nervous system in the acute phase of myocardial
      infarction].
AB  - The aim of this study was to evaluate how heart rate variability changes during
      acute myocardial infarction (AMI) and whether this change is different in
      anterior and inferior AMI. For this purpose 10 patients with anterior (mean age
      53 +/- 11 years) and 11 patients with inferior (mean age 55 +/- 11 years) AMI
      underwent 2 consecutive 24-hour Holter recordings (H1, H2) which started, at
      most, 6 hours after the onset of symptoms and a further two H at the 10th (H3),
      and 28th day (H4) of AMI. None of the patients suffered from diabetes or was
      taking beta-blockers. The standard deviation of the RR intervals (SDRR) for a 24
      hour period was evaluated for each H in the group of patients with anterior and
      inferior AMI. In H1, SDRR was statistically lower in anterior compared to
      inferior AMI (64 +/- 20 versus 106 +/- 27; p < 0.0001). No statistically
      significant differences were found in H2 between the anterior and inferior AMI
      (72 +/- 19 versus 76 +/- 14), due to a reduction in SDRR in inferior AMI: from
      106 +/- 27 in H1 to 76 +/- 14 in H2; p < 0.002. No statistically significant
      changes were present in anterior AMI patients between H1 and H2 (64 +/- 20 versus
      72 +/- 19). SDRR recovers at H3 increasing in both groups (anterior: 101 +/- 28,
      p < 0.001; inferior: 108 +/- 29, p < 0.004). No further significant changes in
      SDRR were present at H4 for either group (anterior 117 +/- 30; inferior: 118 +/-
      31).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7634272
TI  - [Assessment of the autonomic nervous system after infarction and its prognostic
      significance].
AB  - Recently there has been increased interest in the analysis of heart rate
      variability (HRV) and baroreflex sensitivity (BRS) for postinfarction risk
      stratification. HRV and BRS are decreased in patients following myocardial
      infarction and both a reduced HRV and a depressed BRS identify a subgroup at
      higher risk of cardiac mortality and arrhythmic events. In a large trial of post
      myocardial infarction patients the relative risk of mortality was 5.3 times
      higher in the group with depressed HRV (standard deviation of normal RR intervals
      over 24 hour recordings < 50 ms) than in the group with preserved HRV. These
      findings were later confirmed by both time domain and power spectral analysis of
      HRV. The predictive value of depressed HRV was found to be independent of other
      established risk predictors including other Holter features and left ventricular
      ejection fraction. By testing reflex vagal activity, in a series of 78 patients
      recovering from a first myocardial infarction, the risk of death increased more
      than 15 times in the presence of a markedly depressed BRS (< or = 3 ms/mmHg). In
      a subsequent study BRS was found to be the most significant predictor of
      induction of sustained monomorphic ventricular tachycardia at programmed
      electrical stimulation. BRS seems to be more valuable than HRV in the prediction
      of arrhythmic events by providing a relative risk four times greater than HRV to
      accurately predict inducibility to ventricular tachycardia. Additional data have
      shown that BRS but not HRV did clearly separate postinfarction patients with
      aborted sudden death from similar patients without ventricular tachycardia or
      fibrillation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7634273
TI  - [Isolated systolic hypertension: epidemiologic aspects, prevention, and risk].
AB  - Epidemiological studies have shown since long that around 20% of elderly people
      suffer from isolated systolic hypertension. More recently it was calculated that
      this condition implies a 3 fold increase in the incidence of cerebrovascular
      accidents and a 2.2 fold increase in the incidence of myocardial infarction. This
      is why more attention is now dedicated to this condition by both clinicians and
      research workers, especially since the recent demonstration that its treatment
      may lead to a reduction in morbidity and mortality from cerebrovascular causes.
      Unfortunately it was also shown that antihypertensive drugs are more likely to be
      not so well tolerated in elderly hypertensives as in adults and often worsen the
      quality of life. For this reason a careful selection of the patients to be
      submitted to treatment and a close evaluation of the hypotensive response once
      therapy has been started seem in order. To this end 24-hour blood pressure
      monitoring would seem useful as it gives more reliable information on the usual
      blood pressure of an individual and furthermore it allows the detection of
      orthostatic hypotension and of possible excessive blood pressure falls at night
      which are frequent causes of untoward side effects on one hand and of ischemic
      events on the other.

PMID- 7634274
TI  - [The heart in systolic hypertension].
AB  - Among the various forms of systolic hypertension, the primary hyperkinetic heart
      syndrome (overactivity of the cardiac beta-receptors) and the systolic
      hypertension in the elderly are the more interesting ones. The former, although
      involving subjects in the second or third decade of life, is a separate entity
      from the hyperdynamic phase of primary hypertension. Beta-adrenergic blockade,
      even at very long-term, is able to normalize all the major features of the
      syndrome (systolic hypertension, high cardiac output and systolic ejection rate,
      and variability of the repolarization phase of the electrocardiogram related to
      changes in the cardiac adrenergic tone). Beta-blockade is not curative and the
      syndrome reappears as soon as treatment is interrupted. It is a sort of clinical
      experimental model allowing the following deductions: high cardiac output is able
      to cause systolic hypertension; its persistence does not promote the development
      of an elevated systemic vascular resistance; although exposed to some of the
      stimuli that promote cardiac hypertrophy, such as increased stress of the
      ventricular wall, very prolonged adrenergic stimulation, activation of the renin
      system, the syndrome does not evolve towards ventricular hypertrophy. Regarding
      isolated systolic hypertension in the elderly, the so called de novo and "burned
      out" hypertension, are currently indicated as the two forms that characterize
      patients in the seventh and eighth decades of life. Both are interpreted as due
      to a loss of capacitance of the arterial system. It follows that the great
      vessels do not propel blood during diastole, thus increasing the hemodynamic
      burden on the left ventricle, prolonging diastole and delaying
      relaxation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7634275
TI  - [Hemodynamics and pressure variability in isolated systolic hypertension].
AB  - Isolated systolic hypertension is a common feature in aged individuals and it has
      been associated with an increased cardiovascular mortality and morbidity. More
      recently it has been shown that this condition is characterized by peculiar
      abnormalities of arterial vessels. For example isolated systolic hypertension is
      associated with a reduction in arterial compliance evident both in muscle
      arteries, like the radial one, and in elastic arteries, like the carotid one. On
      the other side cardiovascular homeostasis is markedly deranged and blood pressure
      variability more marked than in age matched normotensive subjects. Finally, 24
      hour blood pressure monitoring has allowed to exclude that isolated systolic
      hypertension might be merely linked to an exaggerated alarm reaction, showing
      that blood pressure is elevated along the whole 24-hour blood pressure profile.

PMID- 7634277
TI  - Treatment of isolated systolic hypertension.

PMID- 7634276
TI  - Left ventricular remodeling following myocardial infarction.

PMID- 7634278
TI  - [Changed etiopathogenic and clinical features of infective endocarditis].
AB  - The authors report their experience on etiological and clinical aspects of
      infective endocarditis (IE). A series of 182 consecutive patients, including 83
      cases of medical IE, 73 cases of IE in intravenous drug abusers (DA), 22 cases of
      IE on late prosthetic valves and 4 cases of IE on early prosthetic valves were
      evaluated since 1976. Medical IE occurred frequently in the elderly patients and
      in most of the cases (80%) involved natural valves with underlying abnormalities,
      either rheumatic (42%) or degenerative (33%) or malphormative (25%). Pre-existing
      valvular pathology was not needed for IE in DA, occurring in 13%, mainly due to a
      previous IE. In most of the cases IE in DA was a staphylococcal IE (80%) and a
      right-sided IE (77%). Streptococci were frequent agent both in medical and late
      prosthetic valves IE (55%): however, a wide pattern of microorganisms, including
      "unusual" pathogens like nutritionally variant Streptococci, Haemophylus
      parainfluenzae, Haemophylus paraphrophylus, Coxiella burnetii and the so-called
      "non pathogen microorganisms" (e.g. Neisseria sicca) was identified as
      etiological agent. As regards the clinical approach and diagnosis, the Authors
      underline some atypical clinical presentations of IE: the pulmonary presentation,
      occurring in right-sided IE, mainly in DA; the neurological presentation,
      suggesting staphylococcal etiology and left-sided IE; the vasculitis
      presentation, miming connective tissue diseases; the cardiac presentation,
      observed in aortic localization (1 case). One or more severe complications
      occurred in 65% of the patients, contributing to adverse outcomes.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7634280
TI  - [Therapy and prevention of infective endocarditis].
AB  - Antibiotic therapy has improved infective endocarditis prognosis. The observance
      of general rules to choose the more suitable antibiotic drugs, as regard to their
      effectiveness, pharmacodynamic peculiarities and use, is mandatory. If the
      infection is due to antibiotic resistant microorganisms, microbiological analyses
      to estimate the bactericidal effect of the antibiotics, must be carried out.
      Resistance to penicillins, oligopeptides and aminoglycosides makes endocarditis
      produced by Enterococcus spp difficult to treat. The identification of patients
      at risk for infective endocarditis after surgical and invasive instrumental
      procedures, allows to introduce antibiotic prophylaxis regimens which can reduce
      the probability of acquiring the disease.

PMID- 7634281
TI  - Prevention of post-infarction left ventricular remodeling by ACE-inhibitors.
AB  - Left ventricular remodeling post-infarction occurs in at least a third of
      patients post-infarction and is associated with diminished survival and an
      increased incidence of adverse cardiovascular events. This process, which has
      been well described in recent years, can be largely attenuated with the use of
      ACE-inhibitors and with it survival improved and adverse events minimized. Since
      it is currently not possible to identify people at risk from left ventricular
      remodeling, ACE-inhibitors should be administered to all patients within the
      first 48 hours of infarction.

PMID- 7634279
TI  - [Current cardiologic diagnosis of infective endocarditis].
AB  - This report shows the importance of non-invasive techniques in infective
      endocarditis (IE) diagnosis. ECG is quite specific in identifying perivalvular
      extension of infection when conduction system disease is demonstrated but has a
      low degree of sensitivity overall. Our casuistry (76 patients with IE) confirms
      the literature data about the great importance and the utility of transthoracic
      and transesophageal echocardiography to detect vegetation presence or
      complications as abscesses or valvular leaflet perforations. Therefore, these
      techniques are widely applied to predict major clinical events as embolism and
      death or to suggest a surgical therapy. Nuclear medicine studies play a minimal
      role. Magnetic resonance imaging appears to be an effective tool in this setting;
      however, because of a paucity of clinical data, its precise utility has not yet
      been determined.

PMID- 7634282
TI  - [Infective endocarditis today; heart surgery in its treatment: how and when].
AB  - The authors report the experience of 161 surgical cases operated between 1980 and
      1992 because of valve endocarditis. Two hundred and two surgical procedures were
      performed. Patients were divided into two groups: Group I (EN) considered 117
      patients with endocarditis on the native valve; Group II (EP) included 64
      patients with prosthetic endocarditis. In 23 patients the prosthesis was
      implanted for previous endocarditis on the native valve (EP1); in 41 patients the
      prosthesis was implanted for other valve diseases (EP2). Each group was described
      according to sex, age, site of endocarditis, previous cardiac diseases, socio
      economical level, hemodynamic and infective conditions at surgery, etiology of
      endocarditis, surgical indication, pathology report, surgical procedure and
      results. The results were evaluated considering surgical mortality, late
      mortality and recurrence of endocarditis. The main risk factors were correlated
      to overall survival and recurrency. Hospital mortality was 7.6% in EN, 13% in
      EP1, 36.5% in EP2; endocarditis recurrency was 20.3% in EN, 65% in EP1, 19.2% in
      EP2. Sixteen patients with prosthetic endocarditis were submitted to a second
      reoperation with 50% mortality; 4 patients to a third reoperation with 50%
      mortality; 1 patient to a fourth reoperation with no mortality. Actuarial overall
      survival was 40.3% at 12 years in Group EN, 33.3% at 12 years in Group EP1, 73.4%
      at 12 years in Group EP2. Finally the Authors report the experience of 12
      stentless grafts (autologous, homologous and eterologous) implanted between March
      1991 and July 1994 in patients with valve or prosthetic endocarditis with no
      recurrency at 42 months of follow-up.

PMID- 7634283
TI  - [Which is the optimal pressure level to be obtained with antihypertensive
      treatment?].
AB  - To what level blood pressure should be brought by antihypertensive treatment is a
      question with relevant clinical bearing that hypertensiologists have regrettably
      not yet investigated in a direct way. As a consequence of the lack of direct data
      on this problem, a dispute has been going on for some time as to whether a
      decrease in blood pressure below 85 mmHg increases, rather than further
      decreasing, the coronary risk of the hypertensive patients (the "J-curve"
      hypothesis). The problem has been finally approached through the design and the
      initiation of an appropriate large controlled trial, the Hypertension Optimal
      Treatment (HOT) study.

PMID- 7634284
TI  - [Cardiovascular risk in arterial hypertension: role of family history].
AB  - This is a short and non-comprehensive review of clinical, epidemiological and
      experimental observations that support the importance of the genetic background
      in the susceptibility to vascular injury and acute cardiovascular accidents in
      hypertension. In particular, previous observations suggesting the predictive role
      of positive family history are discussed. In addition, we introduce data obtained
      in our laboratory through an experiment based on rat strain crossing. This novel
      approach may provide a well characterized phenotype that allows gene dissection
      in hypertension with specific regard to cosegregation with vascular accidents.

PMID- 7634285
TI  - [Physiopathologic and clinical features of hypertensive cardiopathy].
AB  - Several studies, performed during the past 20 years in different experimental
      animal models of hypertension and in men, have allowed to clarify important
      pathophysiological and clinical aspects of the hypertensive cardiovascular
      disease, i.e. the pathological condition characterized by marked structural and
      functional alterations of the heart induced by arterial hypertension.
      Epidemiological studies have indeed clearly shown that the prevalence of left
      ventricular hypertrophy in large hypertensive population samples is markedly high
      (40-50%) and that the electrocardiographic evidence of cardiac hypertrophy
      adversely affects patient's prognosis, by significantly increasing cardiovascular
      morbidity (myocardial infarction, congestive heart failure and cardiac
      arrhythmias) and mortality (sudden death). It has also been shown that cardiac
      hypertrophy is characterized by profound functional alterations in myocardial
      contractility and impairs neural reflex responses to beta-adrenergic stimulation
      and to deactivation of cardiopulmonary volume receptors, which are involved in
      physiological conditions in blood volume homeostasis control. Finally, several
      interventional studies have unequivocally shown that antihypertensive drugs may
      allow to obtain, even following 3-6 months of treatment, along with a blood
      pressure reduction, a clearcut regression of cardiac hypertrophy. By improving
      cardiovascular hemodynamics and neural control of circulation, regression of
      cardiac structural alterations is associated with a significant reduction in the
      patient's cardiovascular risk profile.

PMID- 7634286
TI  - [Non-hemodynamic mechanisms of cardiovascular risk in the hypertensive patient:
      insulin resistance].
AB  - Insulin resistance is a condition which is present in many different diseases all
      characterized by an increased risk of cardiovascular morbidity and mortality.
      Generally, the contribution of insulin resistance to the development of
      cardiovascular pathology is considered to be due to its metabolic consequences.
      However, recent findings suggest alternative mechanisms by which insulin
      resistance could exert its role of cardiovascular risk factor. In fact, it has
      been demonstrated that insulin resistant hypertensive patients have a sympathetic
      response to euglycemic hyperinsulinemia which is three-fold greater than in
      normal subjects. This phenomenon could represent an important link between
      sympathetic nervous system and arterial hypertension. Furthermore, in normal
      subjects it has been demonstrated that hyperinsulinemia modulates the sympathetic
      induced vascular response and that this effect is lost in insulin resistant
      hypertensives. This latter phenomenon could further worsen the consequences of
      sympathetic overactivity.

PMID- 7634287
TI  - [Non-hemodynamic vascular risk in the patient with arterial hypertension. The
      effects of medical therapy].
AB  - Systemic hypertension is associated with an increased risk of cerebrovascular and
      coronary events. The exact role of antihypertensive therapy in reversing or
      reducing the incremental risk is still a matter of debate. Stroke in hypertension
      can be large vessel disease (atherothrombotic ischemic stroke), or small vessel
      disease resulting in lacunar lesions or an intracerebral haemorrhage. In the
      major trials evaluating the benefits of antihypertensive therapy the entire
      excess risk of stroke (35 to 45%) can be reversed in 3-5 years. Data on coronary
      events are less clearcut but the most recent metanalyses including data from
      trials in elderly patients show that the reduction in coronary events is larger
      and more significant than in previous metanalyses (approximately 16%). ACE
      inhibitors and calcium channel blockers have many potential advantages over
      diuretics and beta-blockers. Their role is under investigation in ongoing
      clinical trials.

PMID- 7634288
TI  - [Physiopathology of recanalization].
AB  - Clinical benefit from coronary recanalization in acute myocardial infarction is
      linked to the restoration of optimal reperfusion. Experimental and clinical data
      demonstrate that the positive effect of coronary recanalization in terms of
      myocardial salvage, functional improvement and reduction in mortality depends on
      the ability to obtain early and complete reperfusion. Phenomena like no reflow,
      intermittent coronary patency, coronary reocclusion, reperfusion damage, residual
      coronary stenosis may reduce the benefit of recanalization.

PMID- 7634289
TI  - [Prevention of post-infarction remodelling with L-carnitine: multicenter study
      CEDIM (L-Carnitine digital echocardiography myocardial infarction)].
AB  - Prevention of post-infarction ventricular remodeling is an important therapeutic
      aim since left ventricular dilatation is one of the most important prognostic
      post-infarction determinants. Early reperfusion and chronic treatment with ACE
      inhibitors are able to limit remodeling by means of two distinct mechanisms.
      Early reperfusion limits the extent of the infarcted area by salvaging a part of
      the myocardial area at risk of necrosis. ACE-inhibition, on the other hand, by
      reducing afterload, facilitates cardiac ejection and therefore tends to reduce
      left ventricular volume. Remodeling could be limited also by drugs which, like L
      carnitine, act, as has been demonstrated by experimental studies, on the use of
      energy substrates both in the area at risk of necrosis and in the area subjected
      to a greater wall stress because of remodeling and which will progressively
      dilate over time. The CEDIM study is a double-blind, randomized, placebo
      controlled, multicentre trial which has involved 36 Heart Divisions. The CEDIM
      study aims at evaluating the effects of L-carnitine on left ventricular function,
      as assessed by echocardiography, in patients with acute anterior myocardial
      infarction.

PMID- 7634290
TI  - [Non-invasive assessment of coronary reperfusion].
AB  - The patency of the infarct-related coronary artery seems to be an important
      prognostic factor after an acute myocardial infarction. Coronary angiography has
      been used until now to assess coronary patency. However, as it is an invasive
      procedure and its optimal timing after fibrinolytic treatment has not been
      established, a noninvasive marker is most desirable. There are a number of
      methods currently used to document coronary reperfusion non-invasively. This
      review discusses the advantages and disadvantages of the classic non-invasive
      methods, like resolution of chest pain, reperfusion arrhythmias, normalization of
      ST segment elevation, and enzymatic determinations. The imaging methods,
      especially echocardiography but also magnetic resonance imaging, offer
      interesting possibilities for the future.

PMID- 7634291
TI  - [Coronary recanalization in acute myocardial infarction: early coronary
      angiography].
AB  - In acute myocardial infarction the early patency of the infarct-related artery is
      positively correlated with improved left ventricular function and survival.
      Coronary artery reperfusion is commonly achieved by intravenous administration of
      thrombolytic agents. Methods of mechanical recanalization, mainly percutaneous
      transluminal coronary angioplasty (PTCA), have been proposed and tested as
      alternative or adjunctive ways to thrombolysis. Early coronary angiography
      provides reliable and irreplaceable information concerning mechanical
      intervention utility and feasibility. Therefore, it is incorporated in the
      mechanical revascularization strategies at various stages in the setting of acute
      myocardial infarction. In the primary, direct PTCA strategy early coronary
      arteriography is done for planning and carrying out mechanical revascularization
      as an alternative to intravenous thrombolytic therapy. This strategy may be
      particularly effective in patients presenting with cardiogenic shock, large
      infarctions, contraindications to thrombolytic therapy, and prior bypass surgery.
      Coronary angiography in evolving myocardial infarction has also been proposed to
      set the stage for rescue PTCA when thrombolysis has proved to be ineffective.
      Nevertheless, there are currently no unequivocal data to judge the value of the
      rescue PTCA strategy. After unsuccessful thrombolysis, this approach should be
      considered in patients with a large infarction, with cardiogenic shock, with left
      ventricular dysfunction and with refractory ischemia. Early, routine coronary
      angiography after lytic recanalization is not recommended. In fact, the strategy
      of immediate arteriography plus PTCA after thrombolytic therapy does not improve
      outcome but leads to several deleterious effects.

PMID- 7634292
TI  - [Prognostic value of early coronary patency].
AB  - According the early-open artery hypothesis, a prompt reperfusion of the ischemic
      zone in evolving acute myocardial infarction leads to a relevant myocardial
      salvage with consequent reduction in mortality. This conception has been shaken
      by the results of GISSI-2 and ISIS-3 trials, in which the same survival was
      observed in patients treated with either streptokinase or rt-PA, in spite of the
      well known superiority of rt-PA over streptokinase in reopening the culprit
      artery. Recently the results of the GUSTO trial have restored the validity of the
      early-open artery hypothesis. This study shows that a better arterial patency
      does in fact produce a better survival, provided that thrombolysis is
      administered very early and reperfusion is fast (with "accelerated" rt-PA) and
      quite complete (TIMI grade 3), goals not achieved in GISSI-2 and ISIS-3 because
      in these studies rt-PA was administered in the traditional, not accelerated, way.

PMID- 7634293
TI  - [Valvular prosthesis: indications and updated protocols for thrombosis
      prophylaxis].
AB  - Anticoagulants of the dicumarol group are the antithrombotic drugs more widely
      employed in patients with prosthetic valves: they have demonstrated a favorable
      activity in the protection from the thromboembolic complications, which depend on
      the lack of biocompatibility between the valvar surfaces and the blood. The lack
      of biocompatibility is temporary in the biological valves, while is permanent in
      the mechanical, therefore requiring an anticoagulation lasting all the life. The
      treatment, on the other hand, can induce side effects, of which the most severe
      is the possibility of hemorrhagic complications, seldom very severe or leading to
      death. The way the patients are treated and the precision of the laboratory
      control, as the INR test, have proved to be the most important factors affecting
      the fate of the valves and of the patients. With a well conducted laboratory
      control a pregnancy has proved possible in female patients with a mechanical
      valve, judiciously alternating heparin, antivitamin K drugs and again heparin
      during pregnancy.

PMID- 7634294
TI  - [Prevention and treatment of deep venous thrombosis: prevention of pulmonary
      embolism].
AB  - Deep vein thrombosis (DVT), if not properly treated, may be complicated by
      pulmonary embolism in about 50% of the cases within 3 months. Therefore,
      effective prevention of pulmonary embolism relies on three cornerstones: correct
      prophylaxis, early diagnosis, and correct treatment of DVT. In prophylaxis of
      DVT, low-dose heparin is effective in preventing postoperatory DVT and pulmonary
      embolism in medium risk operations, and also in "medical" DVT. In high risk
      operations and patients, personalized low-dose heparin, oral anticoagulants and
      especially low-molecular weight heparins have been used. The available controlled
      trials demonstrate that the low-molecular weight heparins are especially
      efficacious and also cost-effective in high risk situations as elective hip
      surgery. Validated techniques for early diagnosis of DVT are phlebography and, in
      symptomatic proximal DVT, also venous echotomography. Therapy of overt DVT is
      usually performed with infusional or subcutaneous heparin at therapeutic doses,
      followed by moderate range oral anticoagulants. In the initial treatment, low
      molecular weight heparins at single subcutaneous daily dosing can substitute for
      standard heparin. Indication to thrombolytic therapy should be restricted to
      selected cases; thrombectomy has limited application. Caval filters may be useful
      in strictly selected indications, especially in presence of contraindications or
      resistance to anticoagulant treatments.

PMID- 7634295
TI  - [Chronic ischemic cardiopathy: antiplatelet agents and anticoagulants, new
      protocols for prevention and treatment].
AB  - The atherosclerotic process is negatively affected by all the components of the
      haemostatic system (vascular, platelets, blood coagulation, fibrinolysis). The
      diseased coronary tree is a high shear rate flow system which, in turn, implies a
      high number of platelet collisions at sites of vascular injury. This a
      distinctive feature of coronary thrombosis and illustrates the relevance of blood
      rheology in thrombosis development. It is appalling how the clinical benefit
      derived from a conceptually simple intervention such as the partial inhibition of
      platelet function or blood coagulation is actually discernible by a crude tool
      such as a clinical trial. Almost all the subgroups take advantage from the
      treatment and coronary as well as non-coronary events are prevented. Although
      strong arguments exist for the chronic use of oral anticoagulants in patients
      with previous myocardial infarction, antiplatelet regimens are more attractive
      because they do not require any particular skill and are unlikely to determine
      haemorrhagic complications. New strategies in the chronic antithrombotic
      treatment of patients with coronary atherosclerosis may involve the pharmacologic
      manipulation of GpIIb/IIIa (or other platelet integrins) as well as the direct
      blockade of thrombin. However it is the combination of different antithrombotic
      agents that appears most promising presently. The combined use of antiplatelet
      and anticoagulant drugs has already been shown to be effective in acute coronary
      syndromes and in patients with prosthetic heart valves. It is hoped that the same
      pattern will be confirmed also in the chronic phase of coronary artery disease by
      ongoing clinical trials.

PMID- 7634296
TI  - [Heart failure and arrhythmia: modalities and indications of prevention of
      thromboembolism].
AB  - Patients with atrial fibrillation are at risk for peripheral embolism. Congestive
      heart failure, a history of hypertension, previous arterial embolism or
      myocardial infarction are related to an increased risk for thromboembolism. Left
      ventricular enlargement and dysfunction, focal akinesia, protruding and mobile
      thrombi, spontaneous echo contrast are echocardiographic predictors of
      thromboembolism in patients with atrial fibrillation. Clinical trials have shown
      that antithrombotic therapy can reduce the rate of embolic events. In patients
      with heart failure the efficacy of antithrombotic therapy has not been tested in
      randomized, prospective trials. However in these patients oral anticoagulants are
      recommendable in the following conditions: atrial fibrillation; rheumatic mitral
      valve disease; previous thromboembolism; left ventricular enlargement and
      dysfunction; mobile and/or protruding thrombi; spontaneous echo contrast. The
      target INR in treated patients should be maintained within a range of 2 to 3
      times the control. A more intense range of intensity of anticoagulation is
      indicated for patients with mechanical prosthetic valves or with relapsing
      thromboembolism. Current estimates of the effects of aspirin vary too much to
      allow any conclusions.

PMID- 7634298
TI  - [Anatomical and functional characteristics of the myocardial interstitial space].
AB  - The extracellular matrix plays an important role in biological processes, for
      example cellular adhesion, proliferation, migration and differentiation. Many of
      the cell-cell and cell-matrix interactions are mediated by extracellular matrix
      components and by their respective membrane receptors. Important
      pathophysiological processes occur through these interactions of which
      ontogenesis tissue differentiation and reconstruction, many inflammatory and
      immunological events and metastatic processes and invasion. The myocardium is
      made of muscular, vascular and connective components that exist in a state of
      equilibrium based on their relative proportions, integral structures, and on
      their physical and chemical characteristics. The Authors have described molecular
      events that lead to the organization of the cardiac tissue in physiological
      conditions and to its reorganization in pathological situation. Furthermore they
      have evaluated the role of fibronectin, a glycoprotein of the extracellular
      matrix in the initial phase of cardiac ischemia.

PMID- 7634297
TI  - [Antithrombotic agents in pregnancy].
AB  - The need for antithrombotic therapy during pregnancy is a challenging problem for
      the clinician. Pregnancy per se is associated with a prothrombotic state, and
      some conditions definitely require anticoagulant treatment. However, all three
      main antithrombotic agents (coumarins, heparin and aspirin) have potential
      serious adverse effects for the mother and fetus. The aim of this review was to
      discuss the modifications of the coagulation system during pregnancy, and try to
      properly state the indications and the best schedule of antithrombotic treatment
      during pregnancy. Presently heparin is considered the anticoagulant of choice for
      the treatment and prevention of venous thromboembolic disorders and in patients
      with congenital or acquired thrombophilic conditions. The use of oral
      anticoagulants is still preferred in women with prosthetic heart valves or atrial
      fibrillation, but they cannot be administered between the sixth and twelfth week
      and in the last month of gestation because of the teratogenic and hemorrhagic
      risks related to their use. Low-dose aspirin is useful for the prevention of pre
      eclampsia, intrauterin growth retardation, and in association with heparin or
      prednisone, for the prevention of abortion in patients with antiphospholipid
      antibodies.

PMID- 7634299
TI  - [Interstitial changes and ventricular hypertrophy in man].
AB  - Left ventricular hypertrophy is accompanied by the remodeling of the collagen
      network. We have studied collagen network in left ventricular hypertrophy
      secondary to aortic stenosis by cardiac catheterization and endomyocardial
      biopsies. We have demonstrated that collagen architecture is abnormal in 2/3 of
      patients with aortic stenosis and is more important than collagen concentration
      in influencing myocardial stiffness and ejection fraction. Furthermore, we
      observed that relaxation and asynchrony were influenced by the degree of
      hypertrophy instead of by the collagen network. The postoperative regression of
      left ventricular hypertrophy and the changes in interstitial tissue after valve
      replacement have been studied in a subgroup of patients. The major finding is
      that the regression of myocardial hypertrophy is a process that occurs over many
      years after correction of primary hemodynamic abnormality. Six to 7 years after
      valve replacement we observed, together with the normalization of diastolic
      stiffness, the complete normalization of interstitial fibrosis that was primarily
      increased (both pre and early postoperatively).

PMID- 7634300
TI  - [Role of interstitial myocardium in ischemia-reperfusion injury: experimental
      data and clinical implications].
AB  - Myocardial interstitium plays an important role in the regulation of cardiac
      function compared with myocytes and it is actively involved in ischemia
      reperfusion damage and in the acute and chronic remodelling during ischemic heart
      diseases. Myocardial post-ischemic oedema seems to interfere in this process.
      Myocardial oedema is able to induce structural alterations, to reduce myocardial
      function and to activate the renin-angiotensin-aldosterone system. Angiotensin II
      and aldosterone seem to be the cause of myocardial fibrosis that is detected
      during ischemic heart disease. Post-ischemic vascular permeability alterations
      have a similar role. In clinical conditions, ACE-inhibitors have important
      effects on cardioreparation and are able to improve cardiac function and reduce
      early and late mortality. The effects of myocardial oedema reduction (i.e.
      hypertonic reperfusion) on ischemia-reperfusion damage and myocardial fibrosis
      are still to clarify. A reduction in myocardial fibrosis may improve
      cardioreparation and prevent congestive heart failure, following ischemic heart
      disease.

PMID- 7634301
TI  - Myocardial collagen matrix remodeling and congestive heart failure.
AB  - In chronic heart failure, the inter-relationship of the renin-angiotensin
      aldosterone system (RAAS) and cardiac growth is of primary clinical interest. In
      the pressure or volume overloaded heart, hypertrophic growth of the myocardium
      includes the enlargement of cardiac myocytes--an adaptation governed by
      ventricular loading. Nonmyocyte cell growth involving cardiac fibroblast may also
      occur but not primarily regulated by the hemodynamic load. Cardiac fibroblast
      activation is responsible for the accumulation of fibrillar type I and type III
      collagens within the interstitium and adventitia of intramyocardial coronary
      arteries. In addition to relaxation abnormalities due to impairment of
      sarcoplasmic Ca(2+)-ATPase activity, this remodeling of the cardiac interstitium
      represents a major determinant of pathological hypertrophy in that it accounts
      for abnormal myocardial stiffness, leading to ventricular diastolic and systolic
      dysfunction and ultimately the appearance of symptomatic heart failure. In vivo
      and in vitro studies suggest that the effector hormones, angiotensin II and
      aldosterone, of the RAAS are primarily involved in regulating the structural
      remodeling of the myocardial collagen matrix. In cultured adult cardiac
      fibroblasts, angiotensin II and aldosterone have been shown to stimulate collagen
      synthesis while angiotensin II additionally inhibits matrix metalloproteinase 1
      activity, which is the key enzyme for interstitial collagen degradation in the
      myocardium. These observations may serve as rationale why angiotensin converting
      enzyme inhibition or blockade of the RAAS represents such remedial therapy in
      congestive heart failure in patients with hypertensive heart disease, post
      myocardial infarction or with dilated cardiomyopathy.

PMID- 7634302
TI  - [Mechanisms of transluminal mechanical coronary recanalization].
AB  - Coronary angioplasty (PTCA) represents one of the most diffuse technique for
      myocardial revascularization in coronary artery disease patients. The principal
      mechanisms, responsible for the luminal increment after successful balloon
      dilatation are stretching of the vessel wall and splitting of the plaque and its
      rearrangement in an increased cross section of the vessel. Soon after balloon
      deflation elastic recoil of the vessel wall might occur at different grades which
      result in a partial loss of the result achieved by balloon PTCA. This phenomenon
      seems to be one of the major factors influencing the acute and long-term results
      of PTCA. Balloon inflation is also followed by endothelial denudation and
      intramural hemorrhage and intramural thrombus apposition. Then, a proliferative
      process takes place which is characterised by intimal and smooth muscle
      proliferation and migration. This process, beside the elastic recoil of the
      vessel wall, might also contribute to restenosis following balloon PTCA. Other
      devices for myocardial revascularization were introduced in the clinical practice
      based on different mechanisms from that of conventional PTCA. Transluminal
      atherectomy (directional, rotational and rotational-ablation) is based on the
      removal of plaque material from the vessel, increasing the lumen and creating a
      smooth surface. By this mechanism of action, plaque splitting and vessel wall
      stretching might be avoided, thus acute and long-term results are supposed to be
      improved as compared to balloon angioplasty. Another device for the removal of
      plaque material is represented by laser angioplasty which utilizes laser energy
      for the evaporation of the atherosclerotic material and the increase of vessel
      lumen without vessel wall stretching and plaque splitting.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7634303
TI  - A new class of therapeutic agents: the angiotensin II receptor antagonists.
AB  - Angiotensin II (Ang II) is the primary mediator of the renin-angiotensin system
      (RAS). Inappropriate control of the RAS is critically involved in the development
      and maintenance of hypertension and congestive heart failure. The actions of Ang
      II are thought to be mediated by specific surface receptors on the various target
      organs. At present, two receptors for Ang II have been firmly established in
      mammals, including man. According to current nomenclature, losartan represents
      the prototype antagonist of the Ang II type 1 (AT1) receptor and does not possess
      significant affinity for the so-called AT2 receptor. Losartan is the first of a
      new class of orally active, nonpeptide Ang II receptor antagonists able to very
      specifically and selectively inhibit the RAS while lacking the agonistic effects
      of the peptide receptor antagonists, e.g. sarlasin, or the bradykinin
      potentiating effects of the angiotensin converting enzyme (ACE) inhibitors.
      Virtually all of the known actions of Ang II, e.g. those defined by Ang II
      itself, saralasin, ACE or renin-inhibitors are blocked by losartan, emphasizing
      the major role of this distinct Ang II receptor subtype in mediating the
      responses of Ang II. The functional correlate of the AT2 receptor remains poorly
      understood. In several models of experimental and genetic hypertension, AT1
      receptor antagonists are effective antihypertensive agents with similar efficacy
      to that of ACE and renin-inhibitors. In animal models of renal disease, AT1
      receptor antagonists significantly decrease proteinuria, protect against diabetic
      glomerulopathy and increase survival in stroke-prone spontaneously hypertensive
      rats.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7634304
TI  - [Clinical pharmacology of angiotensin II antagonists].
AB  - The renin-angiotensin system (RAS) participates in both cardiovascular
      homeostasis and diseases. Angiotensin converting enzyme (ACE) inhibitors have
      been used very successfully in the treatment of hypertension and heart failure.
      The therapeutic effectiveness of these drugs has been ascribed to their action in
      limiting the activity of the RAS and suggests that other pharmacological
      mechanisms that block this system, such as angiotensin II receptor inhibitors,
      could also be of benefit. Some properties of angiotensin II receptor inhibitors
      offer potential advantages over ACE-inhibitors. ACE acts on other substrates in
      addition to angiotensin I (i.e. bradykinin) so that more specific inhibition of
      the RAS can be achieved with selective angiotensin II antagonists. Data on the
      existence of both circulating and tissue RAS have been reported, and non-ACE
      pathways for angiotensin II production have also been described. So, by
      inhibiting the interaction of the biological active peptide at its receptor
      level, an angiotensin II receptor antagonist will inhibit the RAS independently
      of the source or route of angiotensin II synthesis. Peptide angiotensin II
      antagonists were first reported 20 years ago and the best studied was saralasine;
      they are potent and selective blockers of angiotensin II responses, but their
      lack of oral activity, short duration of action and the concomitant partial
      agonistic activity limited their clinical use. Now are available nonpeptide
      angiotensin II antagonists with attributes appropriate for clinical development.
      The preliminary evaluation of these new selective nonpeptide angiotensin II
      antagonists show their potential therapeutic role in many cardiovascular diseases
      in which the RAS is involved.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7634306
TI  - Theoretical basis for the use of angiotensin II antagonists in the treatment of
      heart failure.
AB  - Angiotensin converting enzyme (ACE) inhibitors have been shown to improve
      morbidity and mortality in patients with heart failure. However, despite the
      demonstrated clinical benefits many physicians are reluctant to prescribe ACE
      inhibitors to the mostly elderly heart failure patients due to concern for side
      effects which may be related to ACE-inhibitor-induced bradykinin accumulation.
      Angiotensin II receptor antagonists may provide more effective blockade of the
      renin-angiotensin-aldosterone system without causing bradykinin accumulation and
      thus associated side effects. The potential benefits of treating heart failure
      patients with an angiotensin II receptor antagonist instead of or in addition to
      an ACE-inhibitor are discussed.

PMID- 7634305
TI  - [Clinical experience with angiotensin II antagonists in arterial hypertension].
AB  - Theoretical considerations and experimental data suggest that AT1-antagonists can
      offer the same advantages as ACE-inhibitors in the treatment of hypertensive
      patients without causing side effects such as angioedema and cough. The
      pharmacokinetic properties of these drugs suggest that AT1-antagonists can be
      given once-daily. Preliminary data obtained with losartan indicate that this
      drug, given once daily, significantly reduced blood pressure with a favourable
      trough to peak ratio. Moreover the hypotensive effect of this drug was similar to
      that exerted by other hypotensive drugs currently employed in the treatment of
      hypertensive patients. Losartan can be usefully combined with a thiazide diuretic
      inducing an additive antihypertensive effect. No negative effect on lipid and
      glucose profiles was recorded. Furthermore, losartan exerted an uricosuric
      action, thus reducing serum uric acid. Preliminary data suggest that the
      incidence of cough in patients treated with losartan was similar to that observed
      in patients receiving placebo or a thiazide diuretic. Although these data need to
      be confirmed by ongoing and future studies, it is tempting to hypothesize that
      this new class of antihypertensive drugs can offer a further useful tool in the
      treatment of hypertensive patients.

PMID- 7634309
TI  - [Primary percutaneous transluminal coronary angioplasty in acute myocardial
      infarction: immediate and short-term results. National experience].
AB  - Direct percutaneous transluminal coronary angioplasty (PTCA) in the early phase
      of acute myocardial infarction (AMI) has till now a relatively limited use,
      mainly because of logistic problems, in comparison with systemic thrombolysis.
      The aim of this paper was to discuss the role direct PTCA during AMI, based on
      the most recent international experience. In brief, the major benefits of direct
      PTCA are the high percentage of recanalization (90%), optimal recanalization
      quality, the absence of contraindications in most cases; in patients with
      cardiogenic shock the mortality is lowered from 80% to 40-45%; absence of
      haemorrhagic stroke and lower incidence of cardiac ischemic events and urgent
      coronary artery bypass grafting (CABG) are seen in short-term follow-up. We also
      present the whole series of 22 Italian centers, all of which has wide experience
      of PTCA, but not performing it on a routine bases in AMI. It concerns of 721
      patients, 389 with single-vessel disease, 198 with double-vessel disease and 105
      with triple-vessel disease. Twenty patients presented left main disease and 147
      patients were in cardiogenic shock. Palmaz-Schatz stent was implanted in 31
      cases; 3 Simpson atherectomy were performed. In 24 cases the PTCA was carried out
      as a "bridge" to emergency CABG, in the presence of triple-vessel disease. Among
      the group without cardiogenic shock 400 procedures were direct, 164 were rescue
      PTCA (within 12 hours). Angiographic success (residual stenosis < or = 50%) was
      obtained in 92 e 89% of cases respectively. In 147 patients with cardiogenic
      shock success was 74%. Mortality was 2.8% in patients without shock and 48% in
      patients with shock.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7634307
TI  - [Stable angina: long-term results].
AB  - We report on 345 patients who underwent percutaneous transluminal coronary
      angioplasty (PTCA) for stable angina in a 5-year period, with an average follow
      up of 34 months (range 12-72). The primary success rate was 94.5%. The late
      mortality and incidence of myocardial infarction were 1.5% and 2.1% respectively.
      The rate of recurrence of angina was 34.5% and required PTCA (28.5%) and/or
      coronary artery bypass grafting (7%). At the end of follow-up 79.5% of patients
      were free from angina and a further 10% had improved. Our data confirm the
      importance of PTCA in stable angina.

PMID- 7634308
TI  - [Unstable angina: immediate and mid-term results].
AB  - Coronary angioplasty (PTCA) for unstable angina is a procedure having good
      anatomical and clinical success. Best immediate results are achieved after a
      clinical "cooling" of the unstable phase, by means of intravenous heparin and
      acetylsalicylic acid. Coronary thrombolysis has no role in improving results of
      PTCA in unstable angina. Incomplete revascularization is safe and clinically
      effective in the acute phase, and staged procedures are recommended if two or
      more vessels are to be treated. Restenosis rate seems to be higher in unstable
      patients, especially in those who are on refractory phase.

PMID- 7634310
TI  - [Percutaneous transluminal coronary angioplasty for postinfarction residual
      ischemia: mid- and long-term results].
AB  - Aim of this study was to assess the long-term results of PTCA in patients with a
      recent myocardial infarction. The study population consisted of 244 consecutive
      patients who underwent a PTCA < or = 30 days after myocardial infarction either
      because of angina (116 patients), or because of provoked ischemia (62 patients),
      or in the absence of both (66 patients). "Simple" balloon angioplasty, without
      adjunctive devices, was performed. Most of the patients were seen at 1 year
      intervals at the outpatient clinic; otherwise information was gathered either
      from the family physician or by telephone. The following events were noted during
      a follow-up of 6-102 months (median 39 months): death, myocardial infarction,
      need for re-PTCA or surgical revascularization, recurrence of angina. Survival
      and event-free curves were calculated according to the method of Kaplan and
      Meier; statistical comparisons between the curves were obtained by the log-rank
      test. Periprocedural deaths, infarctions and surgical revascularizations are
      included in the actuarial curves. Differences were examined between patients with
      Q and non-Q wave infarctions, single vessel versus multivessel disease, left
      ventricular ejection fraction > or 50% versus < 50%. A clinical success was
      achieved in 85% of the procedures. Sixteen patients were lost at follow-up.
      Overall, within the first 30 days and during follow-up, 12 (4.9%) patients died,
      19 (7.7%) suffered from myocardial infarction, 34 (13.9%) required re-PTCA or
      surgical revascularization, and 63 (25.8%) experienced angina again.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7634313
TI  - [Histopathological features of balloon coronary angioplasty].
AB  - Balloon coronary angioplasty revascularization is accomplished through a
      remodelling of the atherosclerotic stenotic wall. Increase in lumen diameter is
      achieved by plaque cracking with intimal dissection, plaque compression and
      medial stretching. Acute complications are frequent (3-8%) and mostly consist of
      occlusive thrombosis occurring upon fissuring of atheromasic plaque, intimal flap
      with invagination, medio-adventitial dissection in the case of tearing of the
      tunica media, and atheromatous embolism. Healing process may be so exuberant as
      to lead to restenosis within a few months.

PMID- 7634311
TI  - [Coronary angioplasty for the recovery of myocardial function after acute
      myocardial infarction: mid- and long-term results].
AB  - Sixty-three patients with previous myocardial infarction and documented
      hypoperfused reversibly dysfunctional myocardium after 201thallium tomography
      and/or echo-dobutamine were candidates to coronary angioplasty. Patients were
      enrolled at four hospitals (Naples, Milan, Pisa and Varese) and evaluated by
      different study protocols, while endpoint (presence of myocardial viability and
      efficacy of coronary angioplasty to improve dysfunctional myocardium) was
      similar. Sixty-two patients underwent successful angioplasty, and early
      evaluation (between 1 and 3 months after procedure) showed the ability of either
      201thallium tomography and/or dobutamine echocardiography, to identify
      hypoperfused reversibly dysfunctional myocardium. Ten patients underwent late
      (after 8 +/- 2 months) evaluation of both wall motion and myocardial perfusion
      showing a sustained improvement in 25/32 hypoakinetic myocardial segments. Our
      data confirm the efficacy of revascularization of hypoperfused dysfunctional
      myocardial segments by coronary angioplasty. Further studies are warranted to
      obtain a better patient stratification and to evaluate the long-term results.

PMID- 7634312
TI  - [Angioplasty in patients already treated with aortocoronary bypass: immediate and
      short-term results].
AB  - Percutaneous transluminal coronary angioplasty (PTCA) is performed in patients
      with prior aortocoronary bypass grafting (CABG) with good results in native
      vessels and in the coronary graft anastomoses, but with high percentage of
      restenosis in the body and in the proximal portion of the grafts. The use of
      intracoronary stents is now spreading, their implantation can improve the
      immediate outcome and may decrease the incidence of restenosis, mostly in the
      body of the graft. In order to evaluate PTCA in CABG patients as to numbers and
      short-term results, the data regarding the year 1993 of 10 Italian Centers are
      presented. In these Centers 3,519 PTCA were performed, 233 (6.6%) of which on
      CABG patients. PTCA has been performed in native vessels in 136 patients and in
      CABG in 126 patients, with 29 patients treated in native vessels as well as in
      CABG. An angiographic and clinical success was obtained in 215 patients (92%). A
      major complication occurred in 11 (4.7%) patients with 8 (3.4%) myocardial
      infarctions, and 3 (1.3%) deaths. Forty-five (19.3%) stents were implanted with
      considerable differences among the Centers. One hundred seventy-three patients
      were followed up for 6 months: 110 (63.6%) were asymptomatic and 57 (32.9%) had
      complained angina; 27 (15.6%) had a second PTCA and 6 (3.5%) had CABG surgery; 1
      patient (0.6%) suffered a myocardial infarction and 7 (4%) died (3 due to CABG
      reinterventions). To evaluate the long-term follow-up, data regarding 58 patients
      submitted to PTCA in the Institute of Cardiology of Bologna since 1985 to 1993
      are showed, with a 3-year follow-up (36 +/- 26 months).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7634314
TI  - [Coronary recanalization: rationale for stents].
AB  - Coronary stenting is a technique complementary to coronary angioplasty, because
      it is successful in the management of the two major limitations of conventional
      balloon dilation, i.e. the acute or threatened closure and the restenosis. The
      currently available intracoronary stents are far from being ideal, mainly for
      their thrombogenicity. During abrupt closure, the bailout stenting has, in most
      of the cases, offered a valuable alternative to emergency coronary artery bypass
      surgery. The major complications after stent insertion are the result of an
      inadequate stent placement, of persistence of intra and/or poststent obstruction
      and of the ineffective anticoagulant therapy. The mechanical support
      (scaffolding) provided by the stent after dilation significantly reduces the
      amount of elastic recoil, and, improving laminar flow, eliminates arterial wall
      shear stress that may contribute to an increase in intimal thickening. Moreover,
      the reduction of arterial cyclical stretching may reduce the rate of neointimal
      proliferation. By sealing the exposed subintimal spaces, stents may minimise the
      formation of local thrombi, and thus also limit their later organization and
      fibrous conversion into part of the restenotic lesion: two recently completed
      randomized trials (STRESS and BENESTENT) confirm the lower rate of restenosis in
      patients treated with single stent placement in de-novo lesions as compared with
      standard balloon angioplasty. The mechanism of stent benefit in reducing
      restenosis rate seems to be the wider initial lumen, which can accommodate a
      greater degree of intimal hyperplasia. In the near future, the improvements of
      the blood and tissue compatibility of the stents, may allow easier
      management.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7634315
TI  - [Rationale for coronary recanalization using transluminal atherectomy].
AB  - Although balloon angioplasty represented a significant advance in the treatment
      of coronary artery disease, this procedure is limited by acute occlusion and late
      restenosis. Among the new devices proposed to overcome the limitations of balloon
      catheters, Simpson's atherocath has the unique property of removing the
      atherosclerotic plaques from the coronary wall. Size and stiffness of the
      terminal portion limit the use of the atherocath to the proximal, non tortuous
      portion of coronary vessels more than 2.5 mm in size. Studies comparing
      atherectomy with balloon angioplasty have demonstrated a greater acute luminal
      gain with atherectomy but have failed to prove a clinical advantage from this
      better initial results. Atherectomy however is a rapidly evolving technology:
      better devices and more aggressive dilating strategies could significantly modify
      the conclusions of the earlier studies. In the meantime atherectomy is providing
      a unique opportunity to study vascular wall pathology.

PMID- 7634316
TI  - [Diagnostic and research potential of directional atherectomy].
AB  - Directional coronary atherectomy (DCA) is the sole technique for the in vivo
      study of coronary artery plaques which are responsible for myocardial ischemia.
      The technique confers the following advantages to the pathologic study of plaque
      samples: the brevity, in general, of the interval between acute myocardial
      ischemia and sampling of the guilty plaque; the absence in samples of autolytic
      phenomena (such as those that affect autopsy samples), an effect that enables the
      use of conventional histopathology, immunohistochemistry and molecular biology;
      the certainty with which the researcher can identify, and thus sample, the truly
      guilty lesions. The drawbacks of the technique are: the fragmentation of the
      plaque; the difficulty the pathologist has in correctly orientating the samples
      in the embedding phase, in distinguishing pre- from post-procedural lesions, and
      in providing a detailed description of the findings. Given the foregoing, the
      diagnostic information to which DCA sampling enables access is as follows: plaque
      derivation--the recognition of whether tissue removed with DCA originates from
      eccentric or concentric, atheromatous of fibrosclerotic, calcified or not
      calcified plaques; histopathology of coronary lesions that cause ischemia with
      regard to: evidence of acute events, such as thrombosis, ulceration and
      hemorrhage, thrombus composition, when it occurs, and definition of its age and
      presence of material deriving from the vascular wall that lies beyond the plaque;
      identification and immunophenotypical characterization of inflammatory
      infiltrates. As regards research, the main implications of DCA are for the study
      of the pathogenetic mechanisms that lead to plaque instability in acute ischemic
      syndromes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7634317
TI  - [Antithrombin therapy in acute coronary syndromes].
AB  - Intracoronary thrombosis is fundamental in the pathogenesis of acute coronary
      syndromes, although the causes of thrombosis are still unclear. As thrombin
      generation is crucial for thrombus formation, the inhibition of thrombin is a
      primary aim to prevent the evolution of an initial repair process into a
      pathological thrombus. Thrombin inhibition can be achieved by several drugs.
      Heparin is the principal antithrombin drug currently used in acute syndromes; it
      acts mainly by binding to antithrombin III and increasing its inhibitory effect
      on thrombin and other coagulation factors. The heparin-antithrombin III complex,
      however, does not inhibit thrombus-bound thrombin; moreover, iv heparin requires
      frequent laboratory monitoring and dose adjustments. Despite these limitations,
      continuous infusion of i.v. heparin has been found to be effective in unstable
      angina and in myocardial infarction, especially when treated with accelerated rt
      PA. New antithrombin drugs that selectively and directly inhibit thrombin are
      hirudin, its synthetic derivate hirulog, and argatroban. These drugs have several
      theoretical advantages over heparin: greater stability of the aPTT--with the need
      for less laboratory monitoring--and greater efficacy--associated mainly with its
      capacity to inhibit clot-bound thrombin. Clinical pilot studies seem to indicate
      a greater antithrombotic efficacy compared with heparin, but a greater number of
      hemorrhagic events in patients with acute myocardial infarction receiving
      thrombolysis. In conclusion, the use of heparin is certainly indicated in
      patients with unstable angina and persistent ischemia and in acute myocardial
      infarction treated with accelerated rt-PA. The use of new antithrombin drugs,
      although promising, requires further clinical evaluation.

PMID- 7634318
TI  - [Assessment of the results during and after coronary recanalization procedures].
AB  - PTCA and new-device angioplasty have dramatically altered the management of
      patients with symptomatic coronary artery disease. Concurrent with the technical
      improvement in coronary angioplasty, the methods used to evaluate procedural
      outcome during and after revascularization have also become more sophisticated.
      Quantitative coronary angiography, angioscopy, and intravascular ultrasound are
      the most important methods for decision making, monitoring the procedure and
      document the final results. However despite their overall research value, these
      qualitative and quantitative techniques may be of limited value to the clinical
      interventional cardiologist and are often complementary or redundant. If a choice
      of these techniques is necessary, on-line quantitative coronary angiography, and
      intravascular ultrasound are certainly the most helpful methods in a Cath Lab to
      evaluate procedural outcome.

PMID- 7634319
TI  - [Role of transesophageal echocardiography in mitral valve repair].
AB  - This study was designed to prove the utility of intraoperative echocardiography
      in the mitral valve repair, that offers many advantages over valve replacement.
      We have assessed 21 consecutive patients, 12 with mitral incompetence and 9 with
      mitral stenosis, undergoing mitral valve surgery over a period of 6 months.
      Preoperative transthoracic and intraoperative transesophageal or epicardial
      echocardiography were performed in all patients. We have assessed, before and
      after repair, the valve morphology, the presence and the severity of mitral
      regurgitation, the pulmonary venous flow, the presence of left ventricular
      outflow tract obstruction. The intraoperative echocardiographic examination
      revealed a successful mitral repair in all patients except one in whom, for the
      persistence of severe mitral regurgitation after repair, valve replacement was
      performed. In none patient systolic anterior motion of mitral apparatus was
      observed. Intraoperative echocardiography seems to be a useful technique to
      assess the adequacy of mitral valve repair before chest closure and, in the case
      of failure, the need for further surgery (valve reconstruction or replacement).

PMID- 7634320
TI  - [Role of transesophageal echocardiography in tricuspid valve repair].
AB  - This paper reviews the role of echocardiography in tricuspid valve repair by
      analyzing the results of three clinical studies. The first investigation was
      performed for assessing the outcome of two surgical techniques in two groups of
      patients who underwent De Vega's suture annuloplasty or Carpentier ring
      implantation. The patients were studied by color Doppler echocardiography after a
      mean follow-up of 28.7 +/- 11.1 months. The results showed lower degree of
      tricuspid valve regurgitation in the group of patients who underwent De Vega
      annuloplasty. The second study demonstrates a new application of transesophageal
      echocardiography (TEE) for optimizing tricuspid valve annuloplasty. Twenty-three
      patients with moderate to severe tricuspid regurgitation underwent De Vega's
      annuloplasty. After cardiopulmonary bypass the tension on the suture was adjusted
      until the surgeon could not feel any regurgitant jet by the intraatrial
      palpation; subsequently, the tension was further adjusted under guidance of TEE.
      The data obtained by the traditional palpation were compared with the data
      obtained by TEE. A significant reduction of residual tricuspid regurgitation was
      obtained by TEE when compared to the data obtained by intraatrial palpation. The
      results showed that the use of TEE was able to optimize the De Vega's
      annuloplasty by reducing residual tricuspid regurgitation. The third study
      investigated tricuspid valve regurgitation commonly observed after orthotopic
      cardiac transplantation (HTX). Aim of the study was to assess the degree of
      regurgitation and its etiology. Twenty-five patients undergoing HTX were studied
      intraoperatively by TEE. The results showed that tricuspid regurgitation occurs
      in most patients immediately after HTX; it is correlated to the ratio recipient
      donor right atrium; surgical techniques which reduce the recipient atrium may
      decrease the occurrence and the degree of tricuspid regurgitation. The above
      mentioned clinical investigations showed a many-sided role of TEE in tricuspid
      valve repair. It provides not only a useful diagnostic tool for evaluating
      residual regurgitation, but it may actively guide the surgical procedures and
      contribute to improve the surgical technique.

PMID- 7634321
TI  - Nuclear export signals and the fast track to the cytoplasm.

PMID- 7634322
TI  - Eph receptor tyrosine kinases, axon repulsion, and the development of topographic
      maps.

PMID- 7634323
TI  - Protease activation during apoptosis: death by a thousand cuts?

PMID- 7634324
TI  - The novel components of the Arabidopsis light signaling pathway may define a
      group of general developmental regulators shared by both animal and plant
      kingdoms.

PMID- 7634325
TI  - Reevaluation of the roles of protein S and Gas6 as ligands for the receptor
      tyrosine kinase Rse/Tyro 3.

PMID- 7634326
TI  - In vitro guidance of retinal ganglion cell axons by RAGS, a 25 kDa tectal protein
      related to ligands for Eph receptor tyrosine kinases.
AB  - The results of previous in vitro experiments indicate that a
      glycosylphosphatidylinositol (GPI)-anchored protein may play an important role in
      the guidance of temporal retinal axons during the formation of the
      topographically ordered retinotectal projection. We have purified and cloned a
      GPI-anchored, 25 kDa glycoprotein that is a good candidate for a molecule
      involved in this process. During the time of innervation by retinal ganglion
      cells, this protein is gradedly expressed in the posterior part of the developing
      tectum. In two different in vitro assay systems, the recombinant protein induces
      growth cone collapse and repulsion of retinal ganglion cell axons. These
      phenomena are observed for axons of temporal as well as nasal origin, indicating
      that an additional activity may be necessary to confer the nasotemporal
      specificity observed in previous assays. We named the protein RAGS (for repulsive
      axon guidance signal). The sequence of RAGS shows significant homology to
      recently identified ligands for receptor tyrosine kinases of the Eph subfamily.

PMID- 7634327
TI  - Complementary gradients in expression and binding of ELF-1 and Mek4 in
      development of the topographic retinotectal projection map.
AB  - Topographic maps with a defined spatial ordering of neuronal connections are a
      key feature of brain organization. Such maps are believed to develop in response
      to complementary position-specific labels in presynaptic and postsynaptic fields.
      However, the complementary labeling molecules are not known. In the well-studied
      visual map of retinal axons projecting to the tectum, the labels are hypothesized
      to be in gradients, without needing large numbers of cell-specific molecules. We
      recently cloned ELF-1 as a ligand for Eph family receptors. Here, RNA
      hybridization shows matching expression gradients for ELF-1 in the tectum and its
      receptor Mek4 in the retina. Binding activity detected with alkaline phosphatase
      fusions of ELF-1 and Mek4 also reveals gradients and provides direct evidence for
      molecular complementarity of gradients in reciprocal fields. ELF-1 and Mek4 may
      therefore play roles in retinotectal development and have properties predicted of
      topographic mapping labels.

PMID- 7634328
TI  - A floral transmitting tissue-specific glycoprotein attracts pollen tubes and
      stimulates their growth.
AB  - Pollen tubes elongate directionally in the extracellular matrix of pistil tissues
      to transport the male gametes from the apically located stigma to the basally
      located ovary for fertilization. The molecular mechanisms underlying directional
      pollen tube growth in the pistil are poorly understood. We have purified a
      glycoprotein, TTS, from tobacco stylar transmitting tissue, which supports pollen
      tube growth between the stigma and the ovary. TTS proteins belong to the
      arabinogalactan protein family, and they polymerize readily in vitro in a head-to
      tail fashion into oligomeric forms. TTS proteins stimulate pollen tube growth in
      vitro and attract pollen tubes grown in a semi-in vivo culture system. In vivo,
      the pollen tube growth rate is reduced in transgenic plants that have
      significantly reduced levels of TTS proteins as a result of either antisense
      suppression or sense cosuppression. These results identify TTS protein as a
      pistil component that positively contributes to pollen tube growth.

PMID- 7634329
TI  - A pollen tube growth stimulatory glycoprotein is deglycosylated by pollen tubes
      and displays a glycosylation gradient in the flower.
AB  - In plant sexual reproduction, pollen tubes elongate from the stigma, through the
      stylar transmitting tissue, to the ovary of the pistil to deliver the male
      gametes for fertilization. TTS protein is a tobacco transmitting tissue
      glycoprotein shown to attract pollen tubes and promote their growth. Here, we
      show TTS proteins adhere to the pollen tube surface and tips, suggesting that
      they may serve as adhesive substrates for pollen tube growth. TTS proteins are
      also incorporated into pollen tube walls and are deglycosylated by pollen tubes,
      suggesting that they may provide nutrients to this process. Within the
      transmitting tissue, TTS proteins display a gradient of increasing glycosylation
      from the stigmatic end to the ovarian end of the style, coincident with the
      direction of pollen tube growth. These results together suggest that the TTS
      protein-bound sugar gradient may contribute to guiding pollen tubes from the
      stigma to the ovary.

PMID- 7634330
TI  - Ceramide synthase mediates daunorubicin-induced apoptosis: an alternative
      mechanism for generating death signals.
AB  - The sphingomyelin pathway, which is initiated by sphingomyelin hydrolysis to
      generate the second messenger ceramide, signals apoptosis for tumor necrosis
      factor alpha, Fas, and ionizing radiation. In the present studies, the anticancer
      drug daunorubicin also stimulated ceramide elevation and apoptosis in P388 and
      U937 cells. Cell-permeable analogs of ceramide, but not other lipid second
      messengers, mimicked daunorubicin in inducing apoptosis. Daunorubicin-stimulated
      ceramide elevation, however, did not result from sphingomyelin hydrolysis, but
      rather from de novo synthesis via activation of the enzyme ceramide synthase. An
      obligatory role for ceramide synthase was defined, since its natural specific
      inhibitor, fumonisin B1, blocked daunorubicin-induced ceramide elevation and
      apoptosis. These studies demonstrate that ceramide synthase activity can be
      regulated in eukaryotes and constitute definitive evidence for a requirement for
      ceramide elevation in the induction of apoptosis.

PMID- 7634331
TI  - Decoding of cytosolic calcium oscillations in the mitochondria.
AB  - Frequency-modulated oscillations of cytosolic Ca2+ ([Ca2+]c) are believed to be
      important in signal transduction, but it has been difficult to correlate [Ca2+]c
      oscillations directly with the activity of Ca(2+)-regulated targets. We have
      studied the control of Ca(2+)-sensitive mitochondrial dehydrogenases (CSMDHs) by
      monitoring mitochondrial Ca2+ ([Ca2+]m) and the redox state of flavoproteins and
      pyridine nucleotides simultaneously with [Ca2+]c in single hepatocytes.
      Oscillations of [Ca2+]c induced by IP3-dependent hormones were efficiently
      transmitted to the mitochondria as [Ca2+]m oscillations. Each [Ca2+]m spike was
      sufficient to cause a maximal transient activation of the CSMDHs and [Ca2+]m
      oscillations at frequencies above 0.5 per minute caused a sustained activation of
      mitochondrial metabolism. By contrast, sustained [Ca2+]c increases yielded only
      transient CSMDH activation, and slow or partial [Ca2+]c elevations were
      ineffective in increasing [Ca2+]m or stimulating CSMDHs. We conclude that the
      mitochondria are tuned to oscillating [Ca2+]c signals, the frequency of which can
      control the CSMDHs over the full range of potential activities.

PMID- 7634333
TI  - The S. pombe cdc15 gene is a key element in the reorganization of F-actin at
      mitosis.
AB  - The S. pombe cdc15 gene is essential for cell division. cdc15ts mutants do not
      form a septum, but growth and nuclear division continue, leading to formation of
      multinucleate cells. The earliest step in septum formation and cytokinesis,
      rearrangement of actin to the center of the cell, is associated with appearance
      of hypophosphorylated cdc15p and formation of a cdc15p ring, which colocalizes
      with actin. Loss of cdc15p function impairs formation of the actin ring. The
      abundance of cdc15 mRNA varies through the cell division cycle, peaking in early
      mitosis before septation. Expression of cdc15 in G2-arrested cells induces actin
      rearrangement to the center of the cell. These data implicate cdc15p as a key
      element in mediating the cytoskeletal rearrangements required for cytokinesis.

PMID- 7634332
TI  - Rbl2p, a yeast protein that binds to beta-tubulin and participates in microtubule
      function in vivo.
AB  - Genetic configurations resulting in high ratios of beta-tubulin to alpha-tubulin
      are toxic in S. cerevisiae, causing microtubule disassembly and cell death. We
      identified three non-tubulin yeast genes that, when overexpressed, rescue cells
      from excess beta-tubulin. One, RBL2, rescues beta-tubulin lethality as
      efficiently as does alpha-tubulin. Rbl2p binds to beta-tubulin in vivo.
      Deficiencies or excesses of either Rbl2p or alpha-tubulin affect microtubule
      dependent functions in a parallel fashion. Rbl2p has functional homology with
      murine cofactor A, a protein important for in vitro assays of beta-tubulin
      folding. The results suggest that Rbl2p participates in microtubule morphogenesis
      but not in the assembled polymer.

PMID- 7634334
TI  - Long-range interaction between two promoters: activation of the leu-500 promoter
      by a distant upstream promoter.
AB  - The leu-500 mutation can be suppressed in S. typhimurium topA. Previous studies
      have demonstrated that the plasmid-borne leu-500 minimal promoter cannot be
      activated in topA mutants unless adjacent (< 250 bp) transcription occurs away
      from the leu-500 promoter (short-range promoter interaction). To search for a
      potential upstream promoter responsible for activation of leu-500 in the
      chromosomal context, we have identified the ilvlH promoter, located 1.9 kb
      upstream of leu-500 (long-range promoter interaction). Different from short-range
      promoter interaction, which is abolished by DNA sequence insertions, the long
      range promoter interaction is mediated by the intervening DNA sequence. These
      studies suggest that the long-range interaction between a pair of divergently
      arrayed promoters is probably mediated by a complex process involving relay of
      DNA supercoiling by the DNA sequence located between the two promoters.

PMID- 7634335
TI  - DNA strand exchange mediated by a RAD51-ssDNA nucleoprotein filament with
      polarity opposite to that of RecA.
AB  - Yeast RAD51 gene functions in genetic recombination and DNA double-strand break
      repair. In vitro, in the presence of ATP and replication protein A, RAD51 protein
      pairs single-stranded DNA (ssDNA) with homologous double-stranded DNA (dsDNA) and
      catalyzes strand exchange between the synapsed DNA partners. Electron microscopic
      analyses show that RAD51 forms helical filaments on both ssDNA and dsDNA, in
      which the DNA is highly extended. However, results presented here indicate that
      only the RAD51-ssDNA nucleoprotein filament is functionally relevant. Strand
      exchange is arrested when heterology is encountered in the duplex partner, and
      analysis of the configuration of the terminal joint thus formed reveals that
      pairing and strand exchange initiate at the 5' end of the complementary strand in
      the linear duplex, a reaction polarity opposite to that of the bacterial
      prototype RecA.

PMID- 7634336
TI  - Identification of a signal for rapid export of proteins from the nucleus.
AB  - Active nuclear import of protein is controlled by nuclear localization signals
      (NLSs), but nuclear export is not understood well. Nuclear trafficking of the
      catalytic (C) subunit of cAMP-dependent protein kinase (cAPK) is critical for
      regulation of gene expression. The heat-stable inhibitor (PKl) of cAPK contains a
      nuclear export signal (NES) that triggers rapid, active net extrusion of the C
      PKl complex from the nucleus. This NES (residues 35-49), fused or conjugated to
      heterologous proteins, was sufficient for rapid nuclear export. Hydrophobic
      residues were critical. The NES is a slightly weaker signal than the SV40 NLS. A
      sequence containing only residues 37-46, LALKLAGLDI, is also sufficient for
      nuclear export. This is an example of a protein-based NES having no obvious
      association with RNA. A similar sequence, LQLPPLERLTL, from Rev, an RNA-binding
      protein of HIV-1, also is an NES.

PMID- 7634337
TI  - Identification of a novel cellular cofactor for the Rev/Rex class of retroviral
      regulatory proteins.
AB  - HIV-1 Rev is the prototype of a class of retroviral regulatory proteins that
      induce the sequence-specific nuclear export of target RNAs. This function
      requires the Rev activation domain, which is believed to bind an essential
      cellular cofactor. We report the identification of a novel human gene product
      that binds to not only the HIV-1 Rev activation domain in vitro and in vivo but
      also to functionally equivalent domains in other Rev and Rex proteins. The
      Rev/Rex activation domain-binding (Rab) protein occupies a binding site on HIV-1
      Rev that precisely matches that predicted by genetic analysis. Rab binds the Rev
      activation domain when Rev is assembled onto its RNA target and can significantly
      enhance Rev activity when overexpressed. We conclude that Rab is the predicted
      activation domain-specific cofactor for the Rev/Rex class of RNA export factors.

PMID- 7634338
TI  - Identification of a novel nuclear pore-associated protein as a functional target
      of the HIV-1 Rev protein in yeast.
AB  - The HIV-1 Rev protein increases the cytoplasmic levels of unspliced and singly
      spliced target transcripts in metazoan systems. Based on experiments that
      indicate a similar function of Rev in the yeast S. cerevisiae, we have identified
      a yeast protein that interacts with the effector domain of Rev. The protein,
      Rip1p, is a novel small nucleoporin-like protein, some of which is associated
      with nuclear pores. Its closest known yeast relative is a nuclear pore component
      also implicated in mRNA transport from nucleus to cytoplasm. Analysis of strains
      that overexpress Rip1p or that are deleted for the RIP1 gene show that Rip1p is
      important for the effect of Rev on gene expression, indicating that the physical
      interaction is of functional significance in vivo. The results suggest that Rev
      directly promotes the cytoplasmic transport of suitable transcripts by targeting
      them to the nuclear pore.

PMID- 7634339
TI  - The host response in graft versus host disease. III. The in vitro induction of
      regulatory cells in chronic murine graft versus host disease.
AB  - Murine graft versus host (GVH) disease takes two forms depending upon the
      parental/F1 strain combination employed. Acute lethal GVH disease is
      characterized by anemia, lymphopenia, hypogammaglobulinemia, profound anti-F1
      cytotoxicity, and the loss of cytotoxic potential against third-party
      alloantigen. In contrast to this, chronic GVH disease is characterized by
      polyclonal B cell activation, autoantibody production, no anti-F1 cytotoxicity,
      and retained cytotoxicity against allotargets. We have previously reported that
      this marked disparity in disease expression results from a radiosensitive host
      cell which protects the F1 mouse from parental anti-F1 CTX in mice undergoing
      CGVH disease. Using an in vitro system to induce the host protective cell, we now
      demonstrate that two distinct Thy-1+ cells emerge which regulate CTX against the
      host. One cell is of host origin, radiation sensitive, and functionally resembles
      a veto cell. The second regulatory cell, of parental origin, is radiation
      resistant and restricted in its ability to suppress anti-F1 CTX. We further
      demonstrate that the emergence of these cells is modulated by competitive
      immunoregulatory influences mediated by T contrasuppressor and I-J+ cells.

PMID- 7634340
TI  - The induction and augmentation of macrophage tumoricidal responses by platelet
      activating factor.
AB  - Platelet-activating factor (PAF) has previously been shown to stimulate
      intracellular signal transductional events similar to the macrophage tumoricidal
      activators interferon-gamma (IFN-gamma) and lipopolysaccharide (LPS). Macrophages
      stimulated with IFN-gamma and LPS utilize various cytolytic mediators in order to
      kill tumor cells. However, PAF has been shown to only induce and enhance tumor
      necrosis factor-alpha (TNF alpha)-mediated cytolysis by macrophages. Therefore,
      the purpose of this study was to determine whether PAF, in comparison with IFN
      gamma and LPS, could stimulate macrophages for both TNF alpha- and non-TNF alpha
      mediated tumoricidal activity. For this, the activation of macrophages for a
      cytolytic response was characterized by the production of TNF alpha and nitric
      oxide (NO2-), as well as, their ability to kill select tumor cells. PAF together
      with IFN-gamma stimulated macrophage secretion of NO2-. In addition, PAF enhanced
      IFN-gamma- and LPS-stimulated NO2- production. PAF, together with IFN-gamma, also
      activated macrophages for tumoricidal activity against TNF alpha-resistant tumor
      cells. In assays to determine the temporal sequence of activation, increased
      tumor cell cytolysis was observed only when macrophages were first treated with
      IFN-gamma. Moreover, PAF enhanced macrophage tumoricidal activity when added with
      LPS and IFN-gamma. With respect to TNF alpha production, macrophages activated
      with high concentrations of PAF stimulated significant levels of TNF alpha
      compared to macrophages without PAF. A similar level was observed following
      multiple additions of a lower concentration of PAF. Also, PAF induced macrophage
      cytolytic activity against a TNF alpha-sensitive tumor cell. In addition, PAF
      significantly enhanced LPS-induced TNF alpha production. Thus, PAF can play a
      modulatory role in the activation for non-TNF alpha-mediated tumoricidal activity
      of macrophages.

PMID- 7634342
TI  - Macrophage colony-stimulating factor (M-CSF) induction of enhanced
      anticryptococcal activity in human monocyte-derived macrophages: synergy with
      fluconazole for killing.
AB  - Induction of enhanced anticryptococcal activity in human monocyte-derived
      macrophages (HMM) by macrophage colony-stimulating factor (M-CSF) and possible
      synergy with fluconazole (FCZ) for killing of Cryptococcus neoformans (CN) was
      studied. Fungistasis by HMM cultured in medium for 3, 5, or 7 days was minimal, 0
      17%. The fungistasis of HMM cocultured with M-CSF at 1000, 5000, or 20,000 U/ml
      for 3, 5, or 7 days was increased significantly (P < 0.02) at all study times and
      by all concentrations. The optimal M-CSF concentration for HMM treatment for
      enhanced fungistasis was 5000 U/ml for Day 3 (84%), whereas 1000 U/ml was
      sufficient with more prolonged HMM culture and M-CSF treatment (Days 5-7). The
      enhancement by M-CSF was seen with four different donors and three patient
      isolates of CN. FCZ at 5 micrograms/ml was fungicidal, 28 +/- 17% (n = 8).
      Killing by FCZ was enhanced by HMM treated with M-CSF 5000 or 20,000 U/ml for 5
      days compared to control HMM, 58% (P = 0.001) and 60% (P = 0.002) vs 48%,
      respectively. This was also seen with HMM cultured with 1000 U/ml M-CSF for 7
      days (P < 0.05). M-CSF also induced in HMM enhancement of fungistasis by lower,
      fungistatic, concentrations of FCZ. These results demonstrate enhancement of
      anticryptococcal activity by HMM treated with M-CSF and synergy with FCZ for
      inhibition and killing. These findings may provide a rationale for combined
      treatment of FCZ and M-CSF against cryptococcosis.

PMID- 7634341
TI  - Regulation of signal transduction and DNA fragmentation in thymocytes by ethanol.
AB  - We demonstrated previously that ethanol enhances apoptosis of murine thymocytes.
      In this report, we determined intracellular cAMP and cytosolic free calcium
      ([Ca2+]i) levels in mouse thymocytes following acute exposure to ethanol and
      investigated the involvement of cAMP, [Ca2+]i, protein kinase A (PKA), and
      protein kinase C (PKC) in thymocyte apoptotic death induced by ethanol. It was
      found that ethanol did not alter basal cAMP levels, but produced a dose
      dependent, prolonged small [Ca2+]i increase within thymocytes. This dose
      dependence of [Ca2+]i increase was paralleled by the magnitude of DNA
      fragmentation induced by ethanol at various concentrations. Additionally, the
      ethanol-enhanced DNA fragmentation was blocked by H7, a PKC inhibitor, but not by
      potent PKA inhibitors having little or no effect on PKC. These data suggest that
      both [Ca2+]i increase and PKC activation triggered by ethanol may belong to the
      signal pathway(s) leading to thymocyte programmed death.

PMID- 7634343
TI  - Membrane-associated lymphotoxin-expressing lymphokine-activated killer cells up
      regulate intercellular adhesion molecule-1 expression on target tumor cells in
      vitro.
AB  - Human lymphokine-activated killer (LAK) cells cultured with interleukin-2 express
      membrane-associated lymphotoxin (mLT) on the cell surface. mLT-lacking (mLT-) LAK
      cells, which are generated by culturing without IL-2 for 24 hr, fully retained
      natural killer (NK) and LAK activity. However, they partially lost their killing
      activity against various tumor cells when compared to mLT-expressing (mLT+) LAK
      cells. An anti-LT but not anti-tumor necrosis factor (TNF) antibody somewhat
      suppressed the killing activity of mLT+ LAK cells against these tumor cells.
      However, an anti-LT antibody did not alter NK or LAK activity of mLT+ LAK cells.
      Anti-CD18 (beta chain of LFA-1) and anti-CD54 (ICAM-1) monoclonal antibodies, by
      inhibiting LAK cell binding to targets, suppressed the killing activity of mLT+
      LAK cells. During the process in the cytotoxic assay, mLT+ but not mLT- LAK cells
      up-regulated ICAM-1 expression on target tumor cells, the effect of which was
      marginally inhibited by anti-TNF and anti-IFN-gamma but not by anti-LT
      antibodies. The up-regulation of ICAM-1 expression elicited by LAK cells on
      target tumor cells was not simply caused by diffused soluble factors but required
      membrane contact of LAK and target cells. Paraformaldehyde-fixed mLT+ but not mLT
      LAK cells up-regulated ICAM-1 expression on target cells. These findings
      indicate that mLT+ but not mLT- LAK cells up-regulate ICAM-1 expression on target
      tumor cells via undetermined membrane factor(s), and this effect appears to be at
      least partially responsible for the higher killing activity of mLT+ LAK cells
      than that of those lacking mLT in vitro.

PMID- 7634344
TI  - Mice with the xid mutation lack the regulatory antibodies that are necessary for
      the induction of contrasuppression.
AB  - We present evidence that mice with X-linked immunodeficiency (xid) lack
      circulating regulatory immunoglobulin (reg Ig) necessary for control of antigen
      specific suppressor T cells (Ts). Previous work demonstrated that reg Ig is one
      component of a serum factor that blocks Ts activity, thereby allowing appropriate
      antibody responses invivo and in vitro. These factors are referred to as
      contrasuppressor factors (CSF). CSF are detected in the serum of mice 3-6 hr
      after immunization with SRBC or can be generated in vitro by combining normal
      mouse serum with supernatants of macrophage-T cell cocultures (M phi-T sup). Data
      presented here demonstrate that CSF were not detectable in the serum of immunized
      xid mice. Serum from xid mice or affinity-purified serum IgG and IgA failed to
      generate CSF in vitro, indicating a lack of reg Ig in xid serum. However, xid T
      cells could block suppression of isotype-specific antibody responses in vitro
      when incubated with functional CSF containing M phi-T sup and CBA/J reg IgG or
      IgA. Similarly, xid macrophages showed no defect in generation of functional M
      phi-T sup in vitro. Finally, CBA/J Vicia villosa adherent (Vv) T cells that were
      incubated with in vitro generated CSF allowed anti-SRBC responses in vivo, when
      adoptively transferred into xid mice, prior to SRBC immunization. These responses
      were comparable to those of normal CBA/J mice immunized with SRBC. Similarly, xid
      mice that received xid T cells treated with CSF and were immunized with SRBC
      generated good anti-SRBC PFC responses. These studies provide strong evidence
      that xid mice lack circulating reg Ig resulting in defective CSF and consequently
      low antibody responses to SRBC, due to dominant Ts activity.

PMID- 7634346
TI  - Defective antigen-receptor-mediated regulation of immunoglobulin production in B
      cells from autoimmune strains of mice.
AB  - B cells are stimulated by antigens or by polyclonal activators such as bacterial
      lipopolysaccharide (LPS) to produce antibody. In nonautoimmune strains of mice,
      LPS-stimulated antibody responses are inhibited by crosslinking the B cell
      antigen-receptor (BCR), while antigen-driven responses are shut down by co
      crosslinking the BCR and the receptor for the Fc portion of IgG (Fc gamma R). BCR
      signals are poor at shutting off LPS-induced antibody production, including anti
      ssDNA antibody production, in B cells from NZB, NZB/WF1, and BXSB lupus-prone
      mice but not MRL/lpr or NZW mice. In the current studies, the defect in NZB B
      cells was shown to be independent of T cells and macrophages. The inheritance
      pattern of resistance to BCR ligation of LPS-induced Ig production in BXSB mice
      could not be assigned to either founding strain. In New Zealand mixed (NZM)
      recombinant inbred mice, slightly but significantly more resistance was found in
      a line (NZM2410) that demonstrates a greater degree of clinical autoimmunity than
      another line (NZM64) with fewer autoimmune problems. The autoimmune defect is
      specific to BCR signals because inhibition of LPS activation by ligation of MHC
      class II occurs normally in NZB B cells. Bypassing the BCR by direct stimulation
      of second messengers with phorbol esters or ionomycin did not overcome the
      defect, suggesting that defects in downstream signaling events, rather than in
      the BCR mechanism itself, are responsible for the reduced ability to inhibit the
      LPS response in NZB B cells. The inability of the BCR signaling pathway to
      control LPS-induced Ig production in NZB mice was apparent at the level of H mu
      chain mRNA for secreted IgM. These results suggest that autoimmunity-associated B
      cell defects in BCR signaling and subsequent regulation of LPS-driven antibody
      responses have a number of inheritance patterns and involve downstream events in
      signaling pathways in B cells. The defect can result in aberrant regulation of H
      mu-chain mRNA levels for secreted IgM production, and may be a predisposing
      factor in murine systemic autoimmune disease.

PMID- 7634345
TI  - The kinetics of cytokine mRNA expression in the retina during experimental
      autoimmune uveoretinitis.
AB  - Experimental autoimmune uveoretinitis (EAU) was induced in Lewis rats and the
      inflamed retinas were examined for IFN-gamma, IL-2, IL-4, and IL-10 mRNA
      production at serial time points using the reverse transcriptase-polymerase chain
      reaction. IFN-gamma, IL-2, IL-4, and IL-10 mRNAs were all detected 24 hr before
      the earliest time point at which histological changes have previously been
      detected. IFN-gamma, IL-2, and IL-4 mRNA expression peaked during the active
      phase of the disease and declined in parallel with lymphocyte numbers as the
      inflammation resolved. IL-10 mRNA levels increased more slowly, reaching a
      maximum at later stages of disease. The observed pattern of cytokine mRNA
      expression in the retina in EAU is similar to that reported in experimental
      autoimmune encephalomyelitis (EAE). The increase in IL-10 mRNA expression in late
      disease may reflect a role in disease resolution as previously proposed in EAE.

PMID- 7634348
TI  - Adhesion molecule expression and adhesion properties of murine intestinal
      intraepithelial lymphocyte hybridomas.
AB  - We used mouse intraepithelial lymphocyte hybridomas (IELH) to study the role of
      adhesion molecules, especially beta 7 integrins, in the adherence of IELH to
      intestinal epithelial cells. Unstimulated 9.1 gamma delta IELH cells expressed
      high levels of CD11a, CD11a/CD18, CD44, and CD45; medium levels of CD45RB and
      integrin alpha 4; low levels of alpha M290, beta 7, and 33D1; and very low levels
      of ICAM-1 and VCAM-1. PHA and TGF-beta stimulated IELH cells--but not control
      BW5147 cells (alpha 4/beta 7 integrin negative fusion partner)--to bind to IEC-18
      and CMT-93 intestinal epithelial cells, but not to renal mesangial cells. The
      binding was partially blocked by mAbs to integrin alpha 4 and/or alpha M290. The
      two mAbs in combination did not completely block the binding, suggesting that
      epitopes not recognized by these two mAbs are also involved in binding. The
      adhesion of 9.1 gamma delta cells to IEC-18 cells was also partially inhibited by
      mAbs to VCAM-1, LFA-1, and CD44, but not by mAbs CD45 and a control rat IgG.
      Thus, IELH may be a useful model system with which to study the role of adhesion
      molecules in the interaction between IEL and intestinal epithelial cells.

PMID- 7634347
TI  - Expression of beta 7 integrins and other cell adhesion molecules on mouse
      lymphocytes and their modulation by a new cytokine, IL-2 receptor-inducing
      factor.
AB  - We explored the role of a new cytokine, IL-2 receptor-inducing factor (IL-2RIF),
      in intestinal mucosal immunity and in the regulation of integrin beta 7 receptors
      on intestinal lymphocytes. Most SIEL (small intestine intraepithelial
      lymphocytes) were M290 (alpha M290 beta 7) positive, while only 10 to 15% of SIEL
      were R1-2 (alpha 4) positive. The expression of alpha 4 (R1-2) and beta 7 (M293)
      but not alpha M290 beta 7 integrin on SIEL was up-regulated by IL-2RIF.
      Incubating SIEL with IL-2RIF resulted in the up-regulation of CD45RB and down
      regulation of CD44. About 50% of LPL (lamina propria lymphocytes) were alpha M290
      beta 7 positive, while only 20% of LPL were alpha 4 positive. The expression of
      alpha M290 beta 7 integrin on LPL was down-regulated and alpha 4 and beta 7
      integrin was up-regulated by IL-2RIF. Incubating LPL with IL-2RIF resulted in the
      up-regulation of CD44 and no significant change of CD11a, CD45, CD45RB, and ICAM
      1. These results suggested that SIEL and LPL may play a different role in
      intestinal mucosal immunity and that IL-2RIF may play an important role in
      regulating the functions of integrins beta 7 on IEL and LPL.

PMID- 7634349
TI  - Crosslinking of CD27 in the presence of CD28 costimulation results in T cell
      proliferation and cytokine production.
AB  - Monoclonal antibodies recognizing CD27, a member of the nerve growth factor
      receptor family, have been observed to enhance or inhibit PHA- or CD3 mAb
      stimulated T cell proliferation. In this study, we investigate the effects of
      CD27 stimulation on the proliferation and cytokine production of T cells
      stimulated simultaneously through CD3, CD2, or CD28. Here we report that
      simultaneous crosslinking of CD27 plus CD28 results in T cell proliferation and
      in the production of IL-2, IL-4, IL-10, and IFN-gamma. CD27 plus CD28 stimulation
      thus introduces a novel Ag-independent pathway of T cell activation. We further
      show that all major T cell subsets (CD4+, CD8+, CD4+CD45RA+, or CD4+CD45RO+ T
      cells) respond to CD27 plus CD28-mediated costimulation. Synergistic effects on T
      cell stimulation are also found when CD27 is crosslinked on cells stimulated
      simultaneously through CD3 or CD2. In further experiments we show that
      crosslinking of CD27 elevates cytoplasmic free Ca2+ levels. Finally, both the CD3
      plus CD27 and the CD28 plus CD27-stimulated T cell proliferation is sensitive to
      inhibition by CsA. Taken together, these data emphasize the importance of CD27
      stimulation in the context of simultaneously received signals through CD3, CD2
      or, most importantly, through CD28. Furthermore, signaling through CD27 appears
      to involve Ca(2+)-dependent mechanisms sensitive to CsA.

PMID- 7634350
TI  - Phenotypic properties and cytokine production of skin-infiltrating cells obtained
      from guinea pig delayed-type hypersensitivity reaction sites.
AB  - In this study, skin-infiltrating cells were prepared from guinea pig delayed-type
      hypersensitivity reaction sites, and their phenotypic properties and cytokine
      production were examined. Our cell preparations contained around 45% nonspecific
      esterase-positive cells and a few skin-derived cells. Skin-infiltrating cells
      produced TNF activity and macrophage chemotactic activity (MCA), whereas resident
      skin cells produced much lower activity. The highest TNF activity was produced by
      skin-infiltrating cells at 2 hr after antigen injection. In contrast, a larger
      amount of MCA was produced by skin-infiltrating cells at 24 and 48 hr than at 2
      hr after antigen injection. These kinetics were in good agreement with our
      previous results regarding cytokine activity in skin extracts. Gel filtration
      analysis and neutralization assay with a monoclonal antibody against human
      macrophage chemotactic factor with a molecular weight of 1 kDa (MCF-1) indicated
      that a guinea pig homologue of human MCF-1 was partially responsible for the MCA.

PMID- 7634352
TI  - In vitro effects of ultraviolet B radiation on human Langerhans cell antigen
      presenting function.
AB  - The effects of ultraviolet B radiation (UBV) on the immune function of human
      epidermal Langerhans cells (LC) were studied by using the mixed epidermal cell
      lymphocyte reaction (MELR). Exposure of both enriched LC suspensions (eLC, 8-20%
      LC) and purified LC suspensions (pLC, 70-90% LC) to increasing doses of UVB
      radiation (25 to 200 J/m2) decreased the proliferative T cell response in a very
      similar dose-dependent way, suggesting that keratinocytes did not play a major
      role in the UVB-induced inhibition of MELR. Supernatants from irradiated cultured
      eLC or pLC failed to inhibit T cell proliferation induced by untreated pLC.
      Furthermore, addition of irradiated eLC to untreated pLC did not affec the
      allogeneic T cell response. Taken together, these results provide evidence that
      in vitro UVB-induced immunosuppression was not mediated by inhibitory soluble
      factors that could affect either LC allostimulatory property or T cell
      proliferative response. UVB irradiation of human LC inhibited the capacity of
      these cells to induce CD4+ as well as CD8+ T cell proliferation. UVB-irradiated
      LC also induced a decreased T cell response to recall antigen or mitogen.
      Moreover, addition of exogeneous cytokines such as IL-1 beta, IL-1 alpha, or IL-2
      did not reverse the defective function of UVB-irradiated LC in MELR. The
      inhibitory effect of UVB radiation on human LC was not related to a decreased HLA
      DR expression. Because cultured LC appeared to be less sensitive than freshly
      isolated LC to UVB-induced suppressive effects, the deleterious effects of UVB
      radiation on human LC allostimulatory properties may be associated with an
      impaired development of LC accessory function.

PMID- 7634351
TI  - Induction of human T cells that coexpress CD4 and CD8 by an immunomodulatory
      protein produced by Actinobacillus actinomycetemcomitans.
AB  - Actinobacillus actinomycetemcomitans, a gram-negative, capnophilic bacterium, is
      associated with several human diseases and is the suspected etiologic agent in
      certain forms of periodontal disease. We have previously shown that this organism
      produces an immunosuppressive factor (ISF) which is capable of inhibiting both T-
      and B-cell activation. Furthermore, these effects appear to be associated with
      the activation of a population of suppressor cells. We now report that the ISF
      induces a unique population of CD4+CD8+ dual-positive T-cells. By utilizing
      multiparameter flow cytometric analysis, we were able to detect the presence of
      dual-positive cells in cultures of human T-cells treated with PHA and ISF. The
      cells appeared within 48 hr and their induction was dependent upon the presence
      of both CD4 and CD8 cells in the culture. Dual expression of CD4 and CD8 was
      stable in that the cells continued to express both surface proteins after being
      sorted and cultured for an additional 24 hr. Phenotypic analysis indicates that
      these cells are also CD3+, CD2+, CD5+, TCR alpha beta+, CD45RA+ (and RO+), and
      CD29+. The dual-positive cells express surface markers associated with T-cell
      activation: CD25+, CD69+, CD71+, and HLA-DR+. In contrast, the cells were
      negative for CD34, CD57, CD56, and CD16. Cell cycle analysis indicates that > 80%
      of the dual-positive cells were in the S phase. Finally, functional analysis of
      these cells indicates that they are capable of suppressing the proliferative
      response of autologous T-cells to PHA.

PMID- 7634354
TI  - [The physiology of activity and research on higher brain functions].

PMID- 7634353
TI  - Dissection of cross-reactivities using a panel of H-2Ld alloreactive T cell
      hybridomas.
AB  - In order to explore the role which class I structure plays in alloreactivity, we
      have generated Ld-reactive T cell hybridomas by fusion of a dm2 anti-BALB/cJ MLR
      with the BW5147 cell line and examined their stimulation by the following class I
      molecules (alpha 1/alpha 2/alpha 3): Lq, Dq, dm1, Ld/Ld/Dd, Lq/Dq/Ld, and
      Q10/Q10/Ld. We found that their specificities differed in their patterns of cross
      reactions and were reasonably representative of those present in the bulk
      population of MLR-generated CTLs. Ld/Ld/Dd and Q10/Q10/Ld stimulated the majority
      of the hybridomas, Lq and dm1 were recognized by over half of the panel, and
      Lq/Dq/Ld stimulated only modestly, while Dq was not recognized by any hybridoma.
      Correlation of these observed reactivities with class I structure suggests that
      putative TCR contact residues may play a significant role in recognition when
      compared to the polymorphic amino acid residues which control pocket specificity
      and peptide binding. Specifically, Lq and Dq possess very similar or identical
      pockets, in contrast to those of dm1 and Q10. However, Q10 has identical TCR
      contact residues to Ld, both on the alpha 1 and alpha 2 alpha helices, unlike Dq
      which is mismatched on both helices. Lq and dm1 are mismatched compared to Ld on
      only one helix. Thus, a molecular rationale for the cross-reactions observed in
      this study involves the direct participation of residues of class I molecules in
      allorecognition.

PMID- 7634355
TI  - [The role of the dopaminergic system in gastrointestinal tract injury].

PMID- 7634356
TI  - [Thoracic electric bioimpedance. Basic principles and physiologic relationships].

PMID- 7634357
TI  - [Troponin as a marker of myocardial injury].

PMID- 7634358
TI  - [Immunity and nutrition].

PMID- 7634359
TI  - [Edward Babak--on the 120th anniversary of his birth].

PMID- 7634360
TI  - [Physiology of activity].

PMID- 7634361
TI  - [The effect of food intake on cardiovascular function. Changes in the blood
      pressure and pulse frequency in neonates and infants during suckling].

PMID- 7634363
TI  - The synthesis of 1-O-(2-N-stearoyl-D-erythro-sphinganine-1-phosphoryl)-2-O-
      (alpha-D-mannopyranosyl-D-myo-inositol: a fragment of the naturally occurring
      inositol-containing glycophosphosphingolipids.
AB  - Chiral mannosylinositol containing sphingophospholipid was synthesized from D
      erythro ceramide and optically active mannosyl-myo-inositol with the use of
      phosphite triester coupling procedure. The optical resolution of racemic 3,4,5,6
      tetra-O-benzyl-myo-inositol to enantiomers was accomplished via diastereomeric
      menthoxyacetic esters. Iodonium ion-promoted glycosylation has been used for the
      preparation of chiral mannosyl-myo-inositol. Bis(diisopropylamino)-2
      cyanoethylphosphine has been applied to the introduction of the phosphodiester
      bond between the primary hydroxyl function of D-erythro-3-O-benzoylceramide and
      the secondary hydroxyl group of optically active and partially benzylated 1-O-(2
      O-alpha-D-mannopyranosyl)- D-myo-inositol.

PMID- 7634362
TI  - Effect of propensity of hexagonal II phase formation on the activity of
      mitochondrial ubiquinol-cytochrome c reductase and H(+)-ATPase.
AB  - The propensity of hexagonal II phase formation plays an important role in the
      activity of mitochondrial ubiquinol-cytochrome c reductase or H(+)-ATPase. The
      respiratory control ratio of reconstituted ubiquinol-cytochrome c reductase or
      the ATP-induced membrane potential of reconstituted H(+)-ATPase became higher as
      the non-bilayer phospholipid phosphatidylethanolamine content of proteoliposomes
      increased. The highest respiratory control ratio or ATP-induced membrane
      potential was obtained in the case of 60-80% phosphatidylethanolamine-containing
      proteoliposomes. Dioleoylphosphatidylethanolamine could significantly enhance the
      respiratory control ratio of ubiquinol-cytochrome c reductase and ATP-induced
      membrane potential of H(+)-ATPase, while no obvious change could be observed when
      dielaidoylphosphatidylethanolamine was used. The bilayer to hexagonal II phase
      transition temperature of ubiquinol-cytochrome c reductase-containing
      proteoliposomes reconstituted with phosphatidylcholine+phosphatidylethanolamine
      increases with decreasing content of phosphatidylethanolamine. Several additives
      such as the bilayer stabilizers, cholesterol 3-sulfate and carbobenzoxy-D-Phe-L
      PheGly, or hexagonal II phase-forming promoters, such as diolein or eicosane, can
      decrease or increase the activity of these two enzyme complexes.

PMID- 7634364
TI  - Plasmalogen oxidation in human serum lipoproteins.
AB  - The content of plasmalogens in lipoproteins--very low density lipoprotein (VLDL),
      low density lipoprotein (LDL) and high density lipoprotein (HDL)--in human serum
      was determined and compared with that after oxidation of the lipoproteins.
      Similarly, the content of alpha-hydroxyaldehydes produced from plasmalogens via
      their epoxids during lipidperoxidation (LPO) was studied. Incubation with Fe+
      +/ascorbate results in a dramatic decrease in plasmalogens that correlates with
      an appropriate increase in alpha-hydroxyaldehydes. VLDL and LDL plasmalogens were
      oxidized to a greater extend (99% decrease) compared to HDL plasmalogens (35%).
      This finding is discussed with respect to atherogenesis and the recently
      postulated protective qualities of plasmalogens.

PMID- 7634365
TI  - Nursing research in South Africa.

PMID- 7634366
TI  - Noise in a neonatal unit: guidelines for the reduction or prevention of noise.
AB  - Advances in medical technology have led to major technological developments in
      the field of neonatal care. Over the past three decades there has been increasing
      concern about noise levels in neonatal intensive care units. The experience of
      working in a neonatal intensive care unit (NICU) and exposure to high noise
      levels of such a unit prompted the researcher to investigate the sources of noise
      further and to explore ways of reducing or preventing the occurrence of such
      noise. The environment of one NICU consisting of a critical care area and a
      "grower type" nursery was surveyed with the aim of establishing noise levels in
      such a unit. A GR (General Radio) 1565-B sound level meter was used to measure
      the noise levels in the NICU and recordings of noise levels were made. Data were
      entered into the checklist each time a sound level was recorded and later
      analysed. In the critical care area sound levels ranged from 64-66 dB (A) (A
      weighted decibel scale) and in the grower nursery from 50-60 dB (A). Recent
      British and American Standards require that the mean noise levels inside the
      incubator should not exceed 60 dB (A) which is safe for the adult human ear
      (Wolke 1987). When compared with the in utero environment the noise levels of the
      neonatal unit are high and potentially hazardous because of the large numbers of
      staff and the amount of equipment present. The main findings of the study were
      that: There is a considerable level of noise in the NICU and this noise persists
      throughout day and night.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7634367
TI  - [Evaluation of selected management skills of senior students in a four-year
      program].
AB  - Due to the composition of the curriculum it is not possible to allocate final
      year students in the four year course to hospital wards where they can practise
      management tasks. In order to overcome this difficulty to a limited degree, a
      plan was devised to give these students the opportunity of practising selected
      management tasks in their free time and an instrument was developed to evaluate
      their knowledge of and insight into these tasks. The instrument was used to
      evaluate the selected management skills of 60 fourth year students. The method
      and results of the project are described in this article.

PMID- 7634368
TI  - [Nursing leadership in perspective].
AB  - South Africa is currently in the process of political change, which places great
      demands on all service sectors. To meet these demands effectively, will require
      dynamic leadership on all levels of service industries. The nursing profession in
      South Africa has produced several significant leaders, of whom Sister Henrietta
      Stockdale and Professor Charlotte Searle are prime examples. However, research
      reports indicate that the profession is currently undergoing a crisis with regard
      to nursing service management. It is assumed that the nursing profession of South
      Africa is experiencing a leadership crisis. It seems as if there are not
      sufficient new leaders to replace those who retire from the profession--which
      means that leadership development is inadequate in the profession. Only a few
      South African research projects have been undertaken with regard to leadership in
      the nursing profession. However, the process of leadership practice in nursing
      has never been researched in South Africa. In this paper a provisional model is
      presented for leadership practice in nursing, which is developed and based on a
      Judeo-Christian-philosophical approach. The dimensions and assumptions of nursing
      leadership practice will be discussed, whereafter the dynamics of nursing
      leadership will be highlighted. Finally the process of leadership will be
      described by suggesting four leadership actions, each with its own principles,
      prerequisites and assumptions. It is recommended that this provisional model be
      exposed to reliability and validity control measures, to develop a final model
      for nursing leadership.

PMID- 7634369
TI  - A case study of primary health care practice in a selected urban area in South
      Africa.
AB  - This paper describes a study where a case study approach using reflective
      critical social theory was adopted to describe the role and function of a urban
      PHC practitioner and to explore the praxis (ie. the underlying personal beliefs,
      values and philosophy) of the practitioner. The analytic interpretation was to
      reflect what it is like (and why this is so), to be an urban PHCP in a rapidly
      changing country. The study used qualitative measures and reflective strategies
      to explore with the PHCP the underlying philosophies, values and beliefs that
      guide her practice. The aim was to provide the practitioner with the opportunity
      to reflect on practice by focussing on day to day experience. The results of this
      study suggest that the practitioner is using a PHC framework during practice and
      participates in community development.

PMID- 7634370
TI  - [Analysis of the perceptions of the frail elderly living in institutions].
AB  - The perception of their nursing care by the aged who resides permanently in
      institutions for the frail-aged, was investigated in this study. An attempt was
      made to investigate, explain and describe the perceptions of the debilitated
      institutionalized elderly person over a broad spectrum of their experiences. A
      clear picture of the experiences of the institutionalized frail-aged person came
      to the fore and a variety of recommendations were made to address the identified
      shortcomings of care.

PMID- 7634371
TI  - Knowledge, attitude and beliefs amongst inhabitants of high density informal
      settlements with regard to sexuality and AIDS in Alexandra township.
AB  - OBJECTIVE: The main purpose of this study was to gain information on the
      knowledge that people living in squatter conditions have about AIDS, their
      attitude towards this disease and their sexual practices. METHOD: The study had
      two parts, in-depth interviews and a survey. The in-depth interviews were held
      with 68 male informal settlement dwellers to obtain information on the type of
      questions to ask in the quantitative part of the study, taking into account the
      sensitivity of the information we were seeking, and how best to phrase these
      questions. For the survey, the 300 male informal settlement residents who were
      interviewed, were located by means of systematic sampling techniques. RESULTS:
      The results of the survey showed that most of the respondents were living in
      squalid conditions, without recreation facilities. They were also likely to have
      had more than one partner (54%). Most of the respondents (90%) had heard about
      AIDS as a disease. Even though they were aware of AIDS as an epidemic in the
      country as a whole, they were not convinced that the disease exists in their
      community, the main reason being that they have never heard about nor seen a
      person with AIDS in the township. CONCLUSION: There is an urgent need for AIDS
      education. But this education cannot take place as a separate activity from other
      upliftment activities in squatter areas.

PMID- 7634372
TI  - [Doctor-patient--patient -doctor relationship: an ethical perspective].
AB  - In this article the author analyses the doctor-patient and patient-doctor
      relationship seen from two ethical viewpoints, namely the question of what is the
      meaning of privacy in the relationship between the doctor and his patient and
      whether the truth should always be told. The author comes to the conclusion that
      privacy in the doctor-patient and patient-doctor relationship is no absolute
      value. Situations do occur when it is in the public interest to make certain
      information known. Aids is only one example in this context. The author also
      emphasises that truth is not a dogma, but a Person. Once again it is stated that
      truth is no absolute value and in some situations it is better not to tell the
      truth- or what people determine the truth to be.

PMID- 7634373
TI  - Differences between the practice of nurses and midwives.
AB  - It is often claimed by midwives that they have an unique role which is
      complementary to but different from the roles of other health care professionals.
      Most of the studies done in midwifery so far lack clarity of definition and
      distinction with regard to process as well as contents. It is important to
      describe the functions of a midwife clearly, because the absence of a clearly
      defined sphere of practice creates problems in the development of an appropriate
      curriculum. The aim of this study is to describe the unique functional activities
      of midwives and compare it with those of the nurse.

PMID- 7634374
TI  - An investigation into competence of families of patients who are nursed at home
      after a stroke with emphasis on their education by the nursing staff.

PMID- 7634375
TI  - [An orientation program for nurses in a private hospital. Phase III].
AB  - An exploratory, descriptive and contextual research study was executed in the
      description of an orientation programme for registered nurses in a private
      hospital. The data for the orientation programme were inferenced from phase 1
      (experience of the registered nurse in a private hospital), and the conceptual
      framework and phase 2 (the expectations of doctors regarding the nursing duties
      of a registered nurse in a private hospital). These data therefore represent the
      population. Data-analysis was done through utilization of the three sets of
      premises as supportive data for the orientation programme. The result is the
      description of the orientation programme, as well as the description of
      guidelines in the operationalization of the programme.

PMID- 7634377
TI  - Effect of tamoxifen on mitoxantrone cytotoxicity in drug-sensitive and multidrug
      resistant MCF-7 cells.
AB  - The influence of the antiestrogen tamoxifen (TAM) on the activity of mitoxantrone
      (MXN), was evaluated against wild-type MCF-7/WT and their multidrug-resistant
      variant MCF-7/ADR cells. Multidrug resistance (MDR) in this cell line which was
      selected for resistance to Adriamycin (ADR), is associated with increased
      expression of P-glycoprotein (P-gp). In a clonogenic assay it was observed that
      TAM (1-10 microM) significantly enhanced the activity of MXN in the MCF-7/ADR but
      not in the drug-sensitive cell line. Isobologram analysis indicated that the
      effect of the combination was additive in the parental MCF-7/WT cells and
      strongly synergistic in the MDR MCF-7/ADR cells. Also, TAM (10 microM) caused a
      three-fold increase in the steady-state levels (Css) of MXN in MCF-7/ADR cells
      but did not modulate MXN levels in MCF-7/WT cells. The observed synergism in MCF
      7/ADR cells was perhaps due to the increase in Css of MXN that may involve
      interaction of TAM with P-gp. The combination of MXN and TAM may be useful in the
      treatment of drug-sensitive and drug-resistant breast cancer.

PMID- 7634376
TI  - Relationship between multidrug resistant gene expression and multidrug resistant
      reversing effect of MS-209 in various tumor cells.
AB  - MS-209 is a novel quinoline compound which can overcome multidrug resistance
      (MDR) both in vitro and in vivo, while having a low level of side effects, and is
      now being evaluated in a clinical phase II study. Reverse transcription
      polymerase chain reaction (RT-PCR) was used to quantitate the expression levels
      of MDR genes in various mouse and human tumor cell lines. The MDR gene and the
      beta actin gene, as the internal reference standard, were coamplified separately,
      and the relative expression of the MDR gene was represented by the MDR/beta actin
      ratio. The in vitro MDR-reversing effect of MS-209 was then compared with the MDR
      gene expression (MDR/beta actin ratio). We found a significant correlation
      between these two parameters. Moreover, a significant correlation was also
      observed between the level of expression of the MDR1 gene and that of P
      glycoprotein in human cell lines. Therefore, the efficacy of MS-209 seems to
      specifically depend on the level of MDR gene expression (P-glycoprotein). From
      these observations, it is suggested that RT-PCR assays of MDR1 gene in tumor
      biopsy specimens might be an effective means to predict the response of tumor
      cells to combination therapy with MS-209.

PMID- 7634378
TI  - Biochemical modulation of 5-fluorouracil with brequinar: results of a phase I
      study.
AB  - Biochemical modulation can increase the efficacy of 5-fluorouracil (5-FU).
      Pizzorno et al. have previously shown that brequinar, a de novo pyrimidine
      synthesis inhibitor, enhances the antitumor effect of 5-FU in vivo [Cancer Res
      52: 1660-1665, 1992]. On the basis of their data, we conducted a phase I study of
      brequinar in combination with 5-FU in patients with refractory solid tumors. The
      initial dose (100 mg/m2) of brequinar was raised in 100-mg/m2 increments in
      cohorts of three assessable patients. The initial dose of 5-FU was 500 mg/m2, but
      escalation was allowed in patients who showed no significant toxic reaction.
      Brequinar was administered over 1 h and 5-FU over 2 h starting 18-20 h after the
      initiation of infusion of brequinar. Treatments were repeated weekly. Responses
      were evaluated after 4 weeks (one course) and then every 8 weeks thereafter.
      Pharmacokinetics of brequinar and determination of plasma uridine levels were
      performed in at least three patients at each dose level. Of the 25 patients
      registered in the study, 21 were assessable for toxicity studies. The dose of
      brequinar was escalated up to 600 mg/m2. In addition, the dose of 5-FU was
      increased to 600 mg/m2 as a result of a lack of a significant toxic reaction in
      the first nine patients. No objective responses were observed. One patient
      developed grade 3 stomatitis, and one developed grade 3 esophagitis at the 400
      and 600 mg/m2 dose of brequinar, respectively. Brequinar produced a dose
      dependent decrease in plasma uridine levels at doses up to 500 mg/m2. No
      additional decrease in plasma uridine occurred with higher doses of brequinar,
      thus suggesting a plateau effect. This observation prompted us to terminate the
      study before reaching the maximum tolerated dose of brequinar. Our data indicate
      that brequinar in doses > or = 400 mg/m2 results in significant biochemical
      modulation. The lack of toxicity seen at these doses of brequinar suggests that
      the initial dose of the effector agent 5-FU should be increased in future
      studies.

PMID- 7634379
TI  - The effect of L-amino acid oxidase on activity of melphalan against an
      intracranial xenograft.
AB  - We have previously shown that diet restriction-induced depletion of large neutral
      amino acids (LNAAs) in murine plasma to 46% of control significantly enhances
      intracranial delivery of melphalan without enhancing delivery to other organs.
      Studies have now been conducted to determine whether more substantial LNAA
      depletion could further enhance intracranial delivery of melphalan. Treatment
      with L-amino acid oxidase (LOX) significantly depleted murine plasma LNAAs:
      phenylalanine, leucine, and tyrosine (> 95%); methionine (83%); isoleucine (70%);
      and valine (46%). Experiments evaluating the intracellular uptake of melphalan
      and high-pressure liquid chromatography quantitation of melphalan metabolites
      revealed, however, that melphalan is rapidly degraded in the presence of LOX, and
      that the timing of the administration of melphalan following the use of LOX to
      deplete LNAAs is crucial. Conditions were found under which LOX-mediated
      degradation of melphalan was minimized and LNAA depletion was maximized,
      resulting in a potentiation of the antitumor effect of melphalan on human glioma
      xenografts in nude mice. Such potentiation could not be obtained using diet
      restriction alone.

PMID- 7634380
TI  - Taxol cytotoxicity on human leukemia cell lines is a function of their
      susceptibility to programmed cell death.
AB  - Taxol is the prototype of a class of antineoplastic drugs that target
      microtubules. It enhances tubulin-monomer polymerization and stabilizes tubulin
      polymers, increasing the fraction of cells in the G2 or M phase of the cell
      cycle. We report that treatment of HL-60 and U937 myeloid cell lines with 1-10
      microM taxol induces DNA fragmentation and the appearance of morphological
      features consistent with the process of apoptosis. Taxol-induced apoptosis is
      inhibited neither by cycloheximide nor by actinomycin D and therefore appears to
      be independent of new protein synthesis. Taxol causes arrest in the G2 phase of
      the cell cycle and affects cell viability but does not induce DNA fragmentation
      in the K562 erythromyeloid cell line. Protein-synthesis inhibitors, colcemid,
      ionomycin, and starvation, known to trigger apoptosis, proved ineffective as
      well. These results suggest that the antineoplastic effect of taxol is mediated
      in susceptible cell lines by induction of the apoptotic machinery and that K562
      partial resistance may depend upon the intrinsic inability of these tumor cells
      to undergo apoptosis.

PMID- 7634381
TI  - Efficacy of topoisomerase I inhibitors, topotecan and irinotecan, administered at
      low dose levels in protracted schedules to mice bearing xenografts of human
      tumors.
AB  - The efficacy of protracted schedules of therapy of the topoisomerase I inhibitors
      9-dimethyl-aminomethyl-10-hydroxycamptothecin (topotecan) and 7-ethyl-10-[4-(1
      piperidino)-1-piperidino]-carbonyloxycamptothecin (irinotecan; CPT-11) were
      evaluated against a panel of 21 human tumor xenografts derived from adult and
      pediatric malignancies. Tumors included eight colon adenocarcinomas, representing
      an intrinsically chemorefractory malignancy, six lines derived from childhood
      rhabdomyosarcoma (three embryonal, three alveolar) representing a chemoresponsive
      histiotype, sublines of rhabdomyosarcomas selected in vivo for resistance to
      vincristine and melphalan, and three pediatric brain tumors. All tumors were
      grown at the subcutaneous site. Topotecan was administered by oral gavage 5 days
      per week for 12 consecutive weeks. The maximum tolerated dose (MTD) was 1.5 mg/kg
      per dose. Irinotecan was given by i.v. administration daily for 5 days each week
      for 2 weeks [(d x 5)2](one cycle of therapy), repeated every 21 days. The MTD for
      three cycles was 10 mg/kg per dose. Treatment was started against advanced
      tumors. Topotecan caused a high frequency of objective regressions in one of
      eight colon tumor lines, whereas irinotecan caused complete regressions (CR) of
      all tumors in three colon lines and a high frequency of CRs in three additional
      lines. Both drugs demonstrated similar activity against rhabdomyosarcoma
      xenografts. Topotecan caused CR of all tumors in four of six lines, and
      irinotecan in five of six lines evaluated. Both agents retained full activity
      against tumors selected for primary resistance to vincristine, but only
      irinotecan retained activity against a tumor selected for primary resistance to
      melphalan. Both agents demonstrated good activity against brain tumor xenografts
      with irinotecan causing CR in two of three lines and topotecan inducing CR in one
      of three lines. Results indicate that low-dose protracted schedules of daily
      administration of these topoisomerase I inhibitors is either equi-effective or
      more efficacious than more intense shorter schedules of administration reported
      previously.

PMID- 7634382
TI  - Effects of sodium thiosulfate on the pharmacokinetics of unchanged cisplatin and
      on the distribution of platinum species in rat kidney: protective mechanism
      against cisplatin nephrotoxicity.
AB  - To investigate the mechanism underlying the protective effect against cisplatin
      (CDDP) nephrotoxicity of its antidote, sodium thiosulfate (STS), the effects of
      STS on the pharmacokinetics of unchanged CDDP and on the distribution of
      unchanged CDDP and high and low molecular mass metabolites (fixed and mobile
      metabolites) in the kidney 1 min after a bolus injection of CDDP (5 mg/kg) to
      rats were studied. A decrease in the plasma concentration of unchanged CDDP and
      an increase in the plasma concentration of mobile metabolites were observed in
      the rats after the bolus injection of CDDP in combination with STS infusion for
      30 min (1200 mg/kg). Although STS accelerated platinum excretion during the first
      10 min after CDDP injection, unchanged CDDP was not excreted in the urine in the
      STS-treated rats. Total kidney platinum 1 min after the bolus injection of CDDP
      was detected mainly as unchanged CDDP (86% of the total platinum) in the rats
      given CDDP alone. However, in the STS-treated rats, the total kidney platinum was
      decreased to 62% of the level in the rats given CDDP alone, and the platinum
      species detected in the kidney were mainly mobile metabolites. Only 24% of the
      total kidney platinum was detected as unchanged CDDP in the STS-treated rats. The
      loss of body weight and increases in BUN and serum creatinine levels usually
      observed after a bolus injection of CDDP were completely prevented by STS
      coadministration. The present study provides information about unchanged CDDP
      pharmacokinetics and the distribution of unchanged CDDP and some of its generic
      metabolites in the kidney when STS is coadministered as an antidote. These
      results show that the protective effect of STS against CDDP nephrotoxicity can be
      attributed to the formation of inactive mobile metabolites by a direct reaction
      between unchanged CDDP and STS in the systemic circulation, resulting in a
      reduction in the amount of unchanged CDDP in the kidney.

PMID- 7634383
TI  - Two polyamine analogs (BE-4-4-4 and BE-4-4-4-4) directly affect growth, survival,
      and cell cycle progression in two human brain tumor cell lines.
AB  - 1,14-Bis-(ethyl)-amino-5,10-diazatetradecane N1,N11-bis(ethyl)norspermine (BE-4-4
      4) and 1,19-bis-(ethylamino)-5,10,15 triazanonadecane (BE-4-4-4-4) are two
      relatively new polyamine analogs synthesized for use as antineoplastic agents. In
      human brain tumor cell lines U-251 MG and SF-767, both agents inhibited cell
      growth, were cytotoxic, induced a variable G1/S block, and depleted intracellular
      polyamines. Since intracellular polyamine depletion did not always correlate with
      growth inhibition, cell survival, or cell cycle progression, it cannot completely
      explain the effects of these agents on growth, survival, and cell cycle
      progression in U-251 MG and SF-767 cells.

PMID- 7634384
TI  - Clinical pharmacology of cytarabine in patients with acute myeloid leukemia: a
      cancer and leukemia group B study.
AB  - The pharmacokinetics of cytarabine (ara-C) were determined in 265 patients with
      acute myeloid leukemia (AML) receiving ara-C (200 mg/m2 per day for 7 days as a
      continuous infusion) and daunorubicin during induction therapy. The mean
      (standard deviation) ara-C concentration at steady-state (Css) and systemic
      clearance (Cl) were 0.30 (0.13) microM and 134 (71) l/h per m2 respectively.
      Males had a significantly faster ara-C Cl (139 vs 131 l/h per m2, P = 0.025) than
      females. Significant correlations were noted between ara-C Cl and the
      pretreatment, peripheral white blood cell count (P = 0.005) and pretreatment
      blast count (P = 0.020). No significant differences in ara-C Css or Cl were noted
      in patients achieving complete remission compared with those failing therapy (P =
      0.315, P = 0.344, respectively). No significant correlations were observed
      between ara-C pharmacokinetic parameters and several indices of patient toxicity.
      Our findings indicate that variability in ara-C disposition in plasma at this
      dosage level does not correlate with remission status or toxicity in patients
      with AML receiving initial induction therapy with ara-C and daunorubicin.

PMID- 7634385
TI  - Cytotoxicity of antitumor platinum complexes with L-buthionine-(R,S)-sulfoximine
      and/or etanidazole in human carcinoma cell lines sensitive and resistant to
      cisplatin.
AB  - Human 2008 ovarian carcinoma cells and the C13 CDDP-resistant subline and human
      MCF-7 breast carcinoma cells and the MCF-7/CDDP CDDP-resistant subline were
      exposed to L-buthionine-(S,R)-sulfoximine (50 microM) for 48 h prior to and
      during exposure for 1 h to the antitumor platinum complexes, cis
      diamminedichloroplatinum(II), carboplatin or D,L-tetraplatin and/or to
      etanidazole (1 mM) for 2 h prior to and during exposure for 1 to the antitumor
      platinum complexes. These modulators alone did not significantly alter the
      cytotoxicity of CDDP toward either parental line. A twofold enhancement in
      cytotoxicity was observed with carboplatin in the 2008 cells and with D,L
      tetraplatin in both parental lines with the single modulators. The modulator
      combination (buthionine sulfoximine/etanidazole) was very effective along with
      D,L-tetraplatin in both the MCF-7 parent and MCF-7/CDDP cell lines where at the
      higher platinum complex concentrations there was 1.5 to 3 logs increased killing
      of cells by the drug plus the modulators compared with the drug alone. Similarly,
      when C13 cells were exposed to CDDP (100 microM) or D,L-tetraplatin (100 microM)
      along with buthionine sulfoximine and etanidazole there was a 2-log increase in
      cell killing compared with exposure to the platinum complex alone. Treatment of
      each of the four cell lines with buthionine sulfoximine decreased both the non
      protein and total sulfhydryl content of the cells. Treatment with the combination
      of modulators did not produce a further decrease in cellular sulfhydryl content
      compared with buthionine sulfoximine alone. The total sulfhydryl content in MCF-7
      cells and 2008 cells exposed to buthionine sulfoximine and etanidazole was 58%
      and 31% of normal and the total sulfhydryl content of MCF-7/CDDP cells and C13
      cells treated the same way was 54% and 23% of normal, respectively. DNA alkaline
      elution was used to assess the impact of exposure to the modulators, buthionine
      sulfoximine and etanidazole, alone and in combination on the cross linking of DNA
      by the antitumor platinum complexes in the MCF-7 and MCF-7/CDDP cell lines.
      Overall, the increases in DNA cross linking factors were greater in the MCF-7
      cells than in the MCF-7/CDDP cells. These results indicate a possible clinical
      potential for this modulator combination.

PMID- 7634387
TI  - Quercetin not only inhibits P-glycoprotein efflux activity but also inhibits
      CYP3A isozymes.

PMID- 7634388
TI  - Glutamine synthetase and hepatocarcinogenesis.

PMID- 7634386
TI  - Organ-specific biotransformation of ormaplatin in the Fischer 344 rat.
AB  - We examined the intracellular biotransformation products of ormaplatin [(d,l
      trans)1,2-diaminocyclohexanetetrachloroplatinum(IV)] (formerly called
      tetraplatin) in liver, kidney, spleen, small intestine, and plasma of the adult
      male Fischer 344 rat. Previous studies have established that the rank order of
      ormaplatin toxicity in Fischer 344 rats is spleen approximately gastrointestinal
      tract > kidney >> liver. Animals were given tritium-labelled drug i.v. at 12.5
      mg/kg, and tissues were harvested 30 min later. The kidney was found to
      concentrate total and cytosolic platinum to a greater extent than any of the
      other tissues. The absolute amount of cytosolic platinum, in micrograms per gram
      tissue, that was irreversibly bound to protein and/or other macromolecules was
      also greatest in the kidney. However, when the amount bound was expressed as a
      percentage of the total cytosolic platinum, the kidney was significantly lower
      than any other tissue. Of the various low molecular mass platinum
      biotransformation species characterized, by far the most abundant were complexes
      of platinum with the sulfur-containing molecules cysteine, methionine, and
      glutathione (GSH). There was more of the methionine complex in the blood plasma
      than in any of the tissues except for the spleen. No significant differences
      among the tissues were detected for the dichloro, cysteine, methionine, or the
      GSH complexes. The tritium-labelled diaminocyclohexane (DACH) carrier ligand
      appeared to remain stably bound to the platinum while in the plasma, as there was
      less free DACH ligand detected in plasma ultrafiltrate than in any tissue
      ultrafiltrate. Among the tissues, the free DACH levels were in the range of 20%
      of the radioactivity recovered from the HPLC column and were not significantly
      different. Consequently, neither biodistribution nor tissue-specific
      biotransformation of ormaplatin provides a ready explanation for the tissue
      specificity of ormaplatin toxicity in Fischer 344 rats. However, in kidney there
      was much less of the reactive PtCl2(DACH) species than has previously been
      reported for the corresponding Pt(NH3)2Cl2 species in cisplatin-treated rats.
      Thus, these data suggest a possible explanation for differences in nephrotoxicity
      induced by cisplatin versus that by ormaplatin.

PMID- 7634389
TI  - GST-P-positive hepatocytes isolated from rats bearing enzyme-altered foci show no
      signs of p53 protein induction and replicate even when their DNA contains strand
      breaks.
AB  - Hepatocytes were isolated from rats with enzyme-altered foci (EAF) in their
      livers and were studied in primary cultures. Cultures were treated with two doses
      of 0.6 mM diethylnitrosamine (DEN) at 1.5 and 24 h. At 48 h the cultures were
      double stained with antibodies against glutathione S-transferase P (GST-P) and
      p53 protein. Ten percent of the GST-P-immunonegative cells were p53
      immunopositive. Thymidine incorporation was blocked in these cells. Both p53
      expression and the block in thymidine incorporation could be eliminated by p53
      antisense oligonucleotides. Less than 1% of the GST-P-positive cells in the same
      cultures were p53-immunopositive. Thymidine incorporation was less affected than
      in GST-P-negative cells. DNA strand breaks were also monitored by an
      immunological technique. Twenty-three percent of the GST-P-negative cells and 7%
      of the GST-P-positive cells were positive for this marker. Seven percent of the
      GST-P-positive cells with DNA strand breaks incorporated thymidine. Virtually
      none of the GST-P-negative cells with DNA strand breaks demonstrated thymidine
      incorporation. We suggest that GST-P-positive cells lack functional p53 protein
      and that this permits cells with damaged DNA to replicate.

PMID- 7634390
TI  - Mutations in the Ada O6-alkylguanine-DNA alkyltransferase conferring sensitivity
      to inactivation by O6-benzylguanine and 2,4-diamino-6-benzyloxy-5
      nitrosopyrimidine.
AB  - Although the human O6-alkylguanine-DNA alkyltransferase (AGT) is very sensitive
      to inactivation by O6-benzylguanine (BG) or 2,4-diamino-6-benzyloxy-5
      nitrosopyrimidine (5-nitroso-BP), the equivalent protein formed by the carboxyl
      terminal domain of the product of the Escherichia coli ada gene (Ada-C) is
      unaffected by these inhibitors. This difference is remarkable in view of the
      substantial similarity between these proteins (33% of the residues in the common
      sequence are identical) and is potentially very important since these inhibitors
      are under development as drugs to enhance the anti-tumor activity of alkylating
      agents. In order to understand the reason for the resistance of the Ada-C
      protein, we have made chimeras between Ada-C and AGT sequences and mutations in
      the Ada-C protein, expressed the altered proteins in an E. coli strain lacking
      endogenous alkyltransferase activity and tested the inactivation of the resulting
      proteins by BG or 5-nitroso-BP. Chimeric alkyltransferase proteins were made in
      which the residues on the amino side of the cysteine acceptor site came from Ada
      C and the residues on the carboxyl side came from AGT and vice versa but these
      did not show sensitivity to BG suggesting that resistance is produced by residues
      in both segments of the protein. Analysis of the Ada-C mutant proteins revealed
      two sites for mutations that confer sensitivity to these inhibitors. One of these
      was tryptophan-336 and the other was residues lysine-314 and alanine-316. Thus,
      when the combined mutations of A316P/W336A were made in the Ada-C sequence, the
      protein was sensitive to inactivation by BG. This A316P/W336A mutant protein was
      even more sensitive to 5-nitroso-BP and the mutant proteins W336A, K314P/A316P
      and A316P could also be inhibited by this drug (in decreasing order of
      sensitivity) although the control Ada-C and a mutant R335S were not inhibited.
      These results provide strong support for the hypothesis that the resistance of
      the Ada-C alkyl-transferase is due to a steric effect limiting access to the
      active site. Insertion of proline residues at positions 314 and 316 and removal
      of the bulky tryptophan residue at position 336 increases the space available at
      the active site and permits these inhibitors to be effective.

PMID- 7634391
TI  - Non-genotoxic hepatocarcinogens stimulate DNA synthesis and their withdrawal
      induces apoptosis, but in different hepatocyte populations.
AB  - Non-genotoxic hepatocarcinogenesis may involve suppression of the hepatocyte
      apoptosis that would normally remove damaged or initiated cells. These protected
      hepatocytes could then remain as preferential targets for promotion by this class
      of compounds. Here we demonstrate clearly that the non-genotoxic liver
      carcinogens and hepatomitogens cyproterone acetate (CPA) and nafenopin, a
      peroxisome proliferator, both suppress the basal level of rat liver apoptosis in
      vivo. After 10 days of dosing with CPA (120 mg/kg/day) or nafenopin (25
      mg/kg/day) there were 0.005 +/- 0.010 and 0.002 +/- 0.021 apoptotic bodies/100
      hepatocytes respectively, compared with 0.031 +/- 0.008 per 100 in controls.
      Concomitant with this suppression of apoptosis, bromodeoxyuridine (BrdU)
      labelling indices and mitotic figures rose, confirming a perturbation of both
      sides of the growth equation between cell death and replication. Withdrawal of
      CPA or nafenopin resulted in a 100- to 200-fold elevation in apoptosis. This was
      inhibited by the re-administration of either compound. To investigate if cells
      protected from apoptosis by non-genotoxic carcinogens are targets for
      replication, we examined the replicative history of the apoptotic bodies
      generated upon withdrawal of CPA or nafenopin. Rats were administered BrdU during
      the hyperplastic phase of compound administration (0-10 days). Livers were
      examined 5 days after compound withdrawal. With both CPA and nafenopin, apoptotic
      bodies and S phase were predominantly in the periportal region. However, despite
      this zonal co-localization, very few (< 10%) of the apoptotic bodies were
      labelled with BrdU. Overall, our data provide in vivo evidence to support the
      hypothesis that non-genotoxic hepatocarcinogens such as CPA and the peroxisome
      proliferators suppress apoptosis. Surprisingly, the majority of the hepatocytes
      generated during compound-induced hyperplasia were protected from apoptosis
      during liver regression. These data contribute to our understanding of clonal
      selection and promotion during non-genotoxic hepatocarcinogenesis.

PMID- 7634392
TI  - Decreased expression of glutathione S-transferases and increased fatty change in
      peroxisomal enzyme-negative foci induced by clofibrate in rat livers.
AB  - Alteration in glutathione S-transferase (GST) isoenzymes was compared with that
      of a peroxisomal enzyme, enoyl-CoA hydratase (ECH), during hepatocarcinogenesis
      caused by clofibrate (CF) administration in male Sprague-Dawley rats. The amount
      of alpha class GST forms, determined by single radial immunodiffusion using anti
      GST 1-2 antibody, was inversely correlated with that of ECH and was decreased at
      week 2 of CF administration to approximately 50% of the value prior to treatment
      and then slightly increased to 70% of the control value by week 15, without
      change thereafter up to 93 weeks. Resolution of GST subunits by high performance
      liquid chromatography revealed an approximately 60% decrease in the amounts of
      subunits 1 and 3 at week 93 and a 25% decrease in the amounts of subunits 2 and
      4. Immunohistochemical staining of rat livers revealed hepatic foci and minifoci
      negative for ECH at week 60 and thereafter. Almost all ECH-negative foci (95.1
      97.9%) were clear cell in character, along with a somewhat lower proportion (68.0
      73.8%) of ECH-negative minifoci. Numerous fat-positive granules were detected in
      78.3% of those lesions exhibiting a clear cell change. Although the amounts of
      GST and ECH exhibited contrasting patterns of alteration in whole livers
      following CF administration, the expression of both alpha and mu class GST forms
      was decreased in the majority of ECH-negative foci at week 93, but were not
      altered in minifoci. The repression of GST forms appeared to be a later event
      than the loss of ECH or the clear cell change in CF-associated hepatic lesions
      and was in clear contrast to the enhanced expression reported for preneoplastic
      lesions induced by mutagenic carcinogens.

PMID- 7634393
TI  - H-ras oncogene mutation spectra in B6C3F1 and C57BL/6 mouse liver tumors provide
      evidence for TCDD promotion of spontaneous and vinyl carbamate-initiated liver
      cells.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent environmental toxin which
      has been found to be non-genotoxic in short term in vitro tests but strongly
      carcinogenic in two stage models of hepatocellular carcinogenesis in female rats.
      Many recent studies have shown that after treatment of mice with various
      genotoxic or non-genotoxic compounds, the H-ras oncogene mutational patterns
      exhibited by hepatocellular tumors appear to vary specifically with the chemical.
      To gain insight into the mechanism of TCDD-associated carcinogenesis, susceptible
      B6C3F1 mice and resistant C57BL/6 mice were treated with a single dose of vinyl
      carbamate (VC) or vehicle, and TCDD was administered once every 2 weeks for 1
      year to half of the animals in each group. Liver tumor prevalence was assessed
      and found to be highest in the VC + TCDD treatment groups, reaching nearly 100%
      at 600 days in both sexes and both strains of mice. DNA was isolated from 20 or
      more frozen liver tumors (if available) from each exposure group and analyzed for
      H-ras mutations in codon 61 by sequencing after PCR amplification of exon 2.
      Fifty-one percent of tumors analyzed from B6C3F1 mice treated with TCDD alone had
      H-ras codon 61 mutations with a pattern similar to that detected in spontaneous
      tumors. Seventy-eight percent of tumors from B6C3F1 mice treated with both VC and
      TCDD had codon 61 mutations, and most mutations were A-->T transversions in the
      second base as observed similarly with VC alone. In the C57BL/6 strain comparable
      results were found in the respective exposure groups. These data suggest that
      TCDD is acting as a promoter of lesions previously initiated either spontaneously
      or by VC. Moreover, the intrinsic resistance of both male and female C57BL/6 mice
      to liver tumor formation seemed to disappear after treatment with TCDD.

PMID- 7634394
TI  - The consequences of fruit and vegetable fibre fermentation on their binding
      capacity for MeIQx and the effects of soluble fibre sources on the binding
      affinity of wheat bran preparations.
AB  - Fruits and vegetables provide dietary fibre some of which is partly soluble in
      the upper gut; in the colon it is highly fermentable. Using alcohol-insoluble
      residues prepared from a range of fruits and vegetables the effects of
      fermentation on the changes in composition and binding capacity have been
      assessed for the hydrophobic mutagen 2-amino-3,8-dimethylimidazo[4,5
      f]quinoxaline (MeIQx). Fermentation was extensive and resulted in destruction of
      most of the pectic polysaccharides. Of the unfermented vegetable fibre only
      cabbage had a measurable hydrophobic binding capacity. The binding capacities of
      unfermented apple, carrot and sugar beet were negligible. After fermentation,
      binding capacities, (per mg of fermented residue), increased. Although fermented
      cabbage was found to have the highest capacity of the fruit and vegetable fibres
      this remained less than the least effective of unfermented wheat bran samples
      which had a relatively high affinity for MeIQx. Mucin inhibited the binding of
      MeIQx to wheat bran fibre but apple fibre did not. The results show that the
      contribution of fruit and vegetable fibre to a hydrophobic binding matrix in the
      colon is insignificant and the suggested harmful effect of fruit and vegetable
      fibre, maintaining hydrophobic mutagens in solution, can be prevented by the
      presence of wheat bran fibre.

PMID- 7634396
TI  - Disposition of butadiene monoepoxide and butadiene diepoxide in various tissues
      of rats and mice following a low-level inhalation exposure to 1,3-butadiene.
AB  - 1,3-Butadiene (BD), a chemical used extensively in the production of styrene
      butadiene rubber, is carcinogenic in Sprague-Dawley rats and B6C3F1 mice. Chronic
      inhalation studies revealed profound species differences in the potency and organ
      site specificity of BD carcinogenesis between rats and mice. BD is a potent
      carcinogen in mice and a weak carcinogen in rats. Previous studies from our
      laboratory and others have shown marked differences between rats and mice in the
      metabolism of BD, which may account for species differences in carcinogenicity.
      The purpose of the present study was to examine the production and disposition of
      two mutagenic BD metabolites, butadiene monoepoxide (BDO) and butadiene diepoxide
      (BDO2), in blood and other tissues of rats and mice during and following
      inhalation exposures to a target concentration of 62.5 p.p.m. BD. BDO was
      increased above background in blood, bone marrow, heart, lung, fat, spleen and
      thymus tissues of mice after 2 h and 4 h exposures to BD. In rats, levels of BDO
      were increased in blood, fat, spleen and thymus tissues. No increases in BDO were
      observed in rat lungs. BDO2, the more mutagenic of the two epoxides, was
      increased in the blood of rats and mice at 2 and 4 h after initiation of exposure
      to BD. In mice, BDO2 was detected in all tissues examined immediately following
      the 4 h exposure. This metabolite was detected in heart, lung, fat, spleen and
      thymus of rats, but at levels 40- to 160-fold lower than those seen in mice.
      Immediately after the 4 h exposure, blood levels of BDO2 were 204 +/- 15 pmol/g
      for mice but were 41-fold lower for rats. In the sensitive mouse target organs,
      heart and lungs, levels of BDO2 exceeded BDO levels immediately after the
      exposure. This study shows that the levels of BD epoxides are markedly greater in
      the mouse BD target organs. The high concentrations of BDO2 in these organs
      suggest that this compound may be particularly important in BD-induced
      carcinogenesis. Thus, although BD is oxidatively metabolized by similar metabolic
      pathways in rats and mice, the substantial quantitative differences in tissue
      levels of mutagenic epoxides between species may be responsible for the increased
      sensitivity of mice to BD-induced carcinogenicity.

PMID- 7634395
TI  - Recombinagenic activity of the phorbol ester 12-O-tetradecanoylphorbol-13-acetate
      in human lymphoblastoid cells.
AB  - The potent mouse skin tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA)
      was examined for its mutagenic and recombinagenic activity at the heterozygous
      thymidine kinase (tk +/-) locus and the hemizygous hypoxanthine
      phosphoribosyltransferase (hprt +/0) locus in the TK6 human lymphoblastoid cell
      line. TPA at concentrations of 0.01-1.0 micrograms/ml induced a low frequency of
      tk mutants showing the slow growth phenotype in a dose-dependent manner, but few
      normal growth tk mutants or hprt mutants. Concentrations of 1.0-10 micrograms/ml
      TPA induced all three types of mutants. The molecular structure of tk mutants
      arising spontaneously or induced by 1.0 and 10 micrograms/ml TPA was investigated
      by Southern hybridization with a human tk cDNA probe: 86% of all mutants arising
      after incubation with 10 micrograms/ml TPA lost the entire active tk allele,
      resulting in loss of heterozygosity (LOH), while 71% of spontaneously arising
      mutants showed LOH. Densitometric analysis indicated that the majority of LOH
      mutants induced by TPA were homozygous at the tk locus (retained two copies of
      the mutant allele), consistent with the occurrence of interchromosomal homologous
      recombination. These results support the hypothesis that tumor promoters such as
      TPA may increase the rate of chromosomal mitotic recombination and hence
      facilitate the segregation of recessive mutations. TPA may thus induce a type of
      genetic instability during the process of tumor promotion that involves enhanced
      recombinagenic activity.

PMID- 7634397
TI  - Intestinal metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in rats:
      Sex difference, inducibility and inhibition by phenethylisothiocyanate.
AB  - The intestinal metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)
      was investigated in male and female Sprague-Dawley (SD) rats and male F344 rats,
      using isolated perfused intestinal segments. [1(-14)C]-NNK at 1 microM was
      metabolized by alpha-hydroxylation, pyridine N-oxidation and carbonyl reduction.
      Jejunal segments from control female rats metabolized 26.2% of the NNK during
      transepithelial transfer to 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL,
      12.2%), 4-(methylnitrosamino)-1-3-pyridyl-N-oxide)-1-butanone (NNK-N-oxide,
      7.7%), 4-oxo-4-(3-pyridyl)-butanol (KAlc, 2.7%), 4-(methylnitrosamino)-1-(3
      pyridyl-N-oxide)-1-butanol (NNAL-N-oxide, 1.8%), 4-oxo-4-(3-pyridyl)butyric acid
      (KA, 1.1%) and 4-hydroxy-4-(3-pyridyl)butyric acid (HA, 0.7%). Ileal segments
      metabolized 20.8% of the NNK during absorption, with no difference in metabolite
      distribution as compared to jejunal segments. In control male SD and F344 rats,
      jejunal presystemic metabolism was 2.3-fold higher (56.4% and 60.8%
      respectively), mainly because of a 4-fold increase in NNAL formation (44.1% and
      48.5%)> total NNK metabolism was also induced in female rats by starvation (84.4%
      metabolites), acetone (89.3%), phenobarbital PB, 75.3%) and Clophen A50 (61%). PB
      and Clophen A50 induced N-oxidation to 38.9% (4 x) and 27.8% (3 x), and to a
      lesser extent NNAL formation and alpha-hydroxylation (2 x), Starvation mainly
      increased N-oxidation with a time-dependent increase from 1 day to 3 days of
      starvation (4 x and 8 x versus controls), whereas alpha-hydroxylation and NNAL
      formation was elevated only after 1 day starvation. Acetone pretreatment (3 days)
      stimulated all three pathways (NNAL 2 x, N-oxidation 4 x, alpha-hydroxylation 4
      x). In male F344 rats, starvation and acetone induced N-oxidation (5 x and 7 x)
      and alpha-hydroxylation (3 x and 5 x), and decreased NNAL formation by 40%,
      probably due to substrate competition or further metabolism of NNAL. In acetone
      induced female SD rats, NNK metabolism was inhibited by in vivo pretreatment with
      phenethylisothiocyanate (PEITC) or in vitro addition of 1% ethanol to the
      perfusate. Both inhibition experiments reduced total metabolism by 20%; N
      oxidation and alpha-dhyroxylation were reduced to values found in control rats,
      whereas NNAL formation increased from 31% to 51%.Inhibition of NNK metabolism by
      PEITC im male F344 rats was less pronounced compared to female SD rats; again a
      decrease in alpha-hydroxylation (6.7% to 3.3%) and N-oxidation (73.6% to 35.3)
      was accompanied by increased NNAL formation (9.8% to 41.0%).(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 7634398
TI  - Inhibition of ligand-induced activation of epidermal growth factor receptor
      tyrosine phosphorylation by curcumin.
AB  - We explored the regulation of epidermal growth factor (EGF)-mediated activation
      of EGF receptor (EGF-R) phosphorylation by curcumin (diferuloyl-methane), a
      recently identified kinase inhibitor, in cultured NIH 3T3 cells expressing human
      EGF-R. Treatment of cells with a saturating concentration of EGF for 5-15 min
      induced increased EGF-R tyrosine phosphorylation by 4- to 11-fold and this was
      inhibited in a dose- and time-dependent manner by up to 90% by curcumin, which
      also inhibited the growth of EGF-stimulated cells. There was no effect of
      curcumin treatment on the amount of surface expression of labeled EGF-R and
      inhibition of EGF-mediated tyrosine phosphorylation of EGF-R by curcumin was
      mediated by a reversible mechanism. In addition, curcumin also inhibited EGF
      induced, but not bradykinin-induced, calcium release. These findings demonstrate
      that curcumin is a potent inhibitor of a growth stimulatory pathway, the ligand
      induced activation of EGF-R, and may potentially be useful in developing anti
      proliferative strategies to control tumor cell growth.

PMID- 7634399
TI  - Pathogenesis of adenocarcinoma induced by gastrojejunostomy in Wistar rats: role
      of duodenogastric reflux.
AB  - The pathogenetic effect of duodenogastric reflux of the development of gastric
      stump carcinoma was studied experimentally. In this animal model, 95 male Wistar
      rats were subjected to a specially designed gastrojejunostomy to divert the
      duodenal contents into the resected stomach through the afferent and efferent
      loop. The rats were fed normally without any carcinogen administration. The
      incidence of adenocarcinomas around the anastomosis of afferent loop was 0% at 10
      weeks, 18.8% at 20 weeks and 34.4% at 40 weeks, so the incidence was apt to rise
      in parallel with passing of the weeks. At 40 weeks, the rats had a significantly
      higher incidence of adenocarcinoma in the gastric mucosa around the afferent loop
      than around the efferent loop (P < 0.05). Of particular interest is that invasive
      growth of the cancerous tissue into the liver was observed in one animal.
      Polypoid lesions called 'atypical hyperplasia' in the present study were similar
      to gastritis cystica polyposa of humans. The development of adenocarcinoma was
      found to be intimately connected with atypical hyperplasia, which might be
      promoted by repeated destruction and regeneration by duodenogastric reflux. These
      results suggest that the direct contact of the duodenal juice with the gastric
      mucosa induces carcinoma in the anastomotic lesion. From the clinical
      perspective, our findings suggest that a surgical technique that minimizes the
      duodenogastric reflux should be chosen.

PMID- 7634401
TI  - Bcl-2 protects murine erythroleukemia cells from p53-dependent and -independent
      radiation-induced cell death.
AB  - To better understand the molecular basis of radiation-induced cell death, we
      studied the role of the bcl-2 oncogene and the p53 tumor suppressor gene in this
      process. A temperature-sensitive mutant of murine p53 (p53Val-135) and/or bcl-2
      was transfected into murine erythroleukemia cells (MEL, DP16-1, which are null in
      p53). We demonstrate that radiation-induced cell death occurs by both p53
      dependent and -independent pathways and overexpression of bcl-2 modulates both
      pathways. When viability was measured 24 h post-radiation, cells that had been
      briefly exposed to wtp53 immediately after X-ray irradiation had decreased
      survival as compared to unirradiated cells expressing wtp53 or X-ray irradiated
      DP16-1 cells. However, at later times X-ray irradiated parental DP16-1 cells also
      had decreased survival compared to the unirradiated control. This decrease in
      survival began 48 h following radiation. Bcl-2 prevented radiation-induced cell
      death in DP16-1 cells expressing wtp53 and delayed radiation-induced cell death
      in DP16-1 cells without wtp53. X-ray irradiated cells expressing wtp53 displayed
      microscopic and biochemical characteristics consistent with cell death due to
      apoptosis. DP16-1 cells which were untransfected or co-transfected with wtp53 and
      bcl-2 displayed characteristics of cells undergoing necrosis. These results
      suggest that radiation-induced cell death occurs by both p53-dependent and p53
      independent pathways. The p53-dependent pathway results in cell death via
      apoptosis and occurs approximately 24 h following radiation. The p53-independent
      pathway does not appear to involve apoptosis and occurs at a later time, starting
      48 h after X-ray exposure. Thus, bcl-2 protects cells from p53-dependent
      radiation-induced apoptotic cell death and attenuates p53-independent radiation
      induced cell death.

PMID- 7634400
TI  - Heterochromatic proteins specifically enhance nickel-induced 8-oxo-dG formation.
AB  - 7,8-Dihydro-8-oxo-2'-deoxyguanosine (8-oxo-dG) was measured as an indicator of
      nickel-induced oxidative base damage in the presence of H2O2. Heterochromatic
      proteins isolated from Chinese hamster liver cells enhanced the formation of 8
      oxo-dG induced by NiCl2 and H2O2 in vitro, whereas euchromatic proteins inhibited
      this reaction. The inhibitory effect of euchromatic proteins on dG oxidation may
      be due to the oxygen radical scavenging effects of low molecular weight protein
      rich fractions. Gel electrophoresis confirmed that histone H1 was present at a
      higher concentration in heterochromatin than in euchromatin. It is believed that
      the presence of nickel-protein complexes in cells is crucial for the formation of
      reactive oxygen species (ROS). We found that Ni2+ binds to histone H1 and core
      histones as determined by 63Ni autoradiography of proteins on nitrocellulose
      membranes. In vitro studies showed that commercially purified histone H1, and to
      a considerably lesser extent core histones, enhanced the NiCl2 and H2O2 catalyzed
      formation of 8-oxo-dG in a reaction containing free dG base. Since histone H1 is
      a lysine- and alanine-rich protein, the levels of 8-oxo-dG induced by NiCl2 and
      H2O2 were studied in the presence of these amino acids and found to be enhanced
      by them. These results suggest that nickel may specifically produce oxidative DNA
      damage in heterochromatin because of the nature of its binding to histone H1 and
      core histones. This selective oxidation of genetically inactive heterochromatin
      may explain why nickel compounds which generate oxygen radicals and oxidize DNA
      bases are inactive in most gene mutation assays.

PMID- 7634402
TI  - Levels of aflatoxin-albumin biomarkers in rat plasma are modulated by both long
      term and transient interventions with oltipraz.
AB  - The validation process for biomarkers to be used for monitoring the efficacy of
      preventive interventions in humans includes assessments of whether levels of the
      biomarker can be modulated in experimental models. From this perspective, the
      influence of two intervention protocols with the chemopreventive agent oltipraz
      on rates of formation and disappearance of aflatoxin-albumin adducts has been
      evaluated in rats chronically exposed to aflatoxin B1. Male F344 rats were
      treated daily with 20 micrograms aflatoxin B1, p.o. for 35 days. The first
      strategy employed a standard, long-term intervention in which basal AIN-76A diet
      was supplemented with 0.05% oltipraz beginning one week before AFB1 treatment and
      continuing throughout the period of carcinogen exposure. In this setting,
      treatment with oltipraz reduced the rate of formation of aflatoxin-albumin
      adducts such that steady-state levels were lowered by > 50% from control values
      of 400 pmol aflatoxin adducts/mg albumin. The time-course for reaching respective
      steady-state levels was unchanged, with or without oltipraz intervention. The
      second intervention strategy utilized a delayed, transient protocol in which
      oltipraz was fed for 2 weeks beginning 1 week after AFB1 dosing began and ending
      2 weeks before AFB1 dosing was completed. This second strategy, which models
      clinical interventions in chronically exposed individuals, produced a steady
      decline in aflatoxin-albumin adduct levels that approached a 50% reduction by the
      end of the AFB1 exposure period. Development of smooth curve functions allowed
      for the estimation of the ratio of effects between the non-intervention and
      intervention groups as well as the simultaneous 90% confidence intervals for the
      aflatoxin-albumin adduct levels. These analyses indicated that long-term
      intervention with oltipraz produced a statistically significant reduction in
      levels of the aflatoxin-albumin biomarker at all times throughout aflatoxin
      exposure. By contrast, a statistically significant decrease in biomarker levels
      was not seen in the delayed, transient intervention protocol until the ninth day
      of the intervention. However, once achieved, significant differences from the
      control group were maintained for the remainder of the aflatoxin exposure period.
      These changes in aflatoxin biomarker levels are consistent with the cancer
      chemopreventive outcomes of these intervention protocols in rats. Collectively,
      these results support the utility of measuring this biomarker as a means for
      assessing the efficacy or chemopreventive interventions in individuals at high
      risk for aflatoxin exposure and development of hepatocellular carcinoma.

PMID- 7634403
TI  - O6-methylguanine-induced replication blocks.
AB  - The ability of Klenow polymerase I, phage T7 polymerase (Sequenase), human
      polymerase alpha, and human polymerase beta to synthesize past (bypass) O6
      methylguanine (O6-meG) lesions was studied in the presence of MgCl2 and MnCl2. An
      end-labeled 16-mer primer was annealed to the 3' end of gel-purified
      oligodeoxyribonucleotide templates (45-mers), each containing a single O6-meG in
      place of one G in the sequence -G1G2CG3G4T-. Extension products were analyzed by
      denaturing polyacrylamide gel electrophoresis and autoradiography. A fraction of
      the products extended by Klenow fragment terminated either opposite or one base
      before O6-meG located at sites 1 and 3. Termination occurred primarily one base
      before O6-meG located at sites 2 and 4. The remaining fractions that bypassed the
      lesions represented full-length product. In control reactions, the O6-meG
      containing templates were annealed with complementary 45-mers, repaired with O6
      alkylguanine DNA-alkyltransferase, annealed with an excess of labeled primer, and
      extended by Klenow fragment. Full-length extension of > 90% was observed with
      each template. Primer extension past O6-meG by DNA polymerase alpha and Sequenase
      was partially blocked in a manner which varied with the site of O6-meG in the
      template while primer extension by DNA polymerase beta was completely blocked (<
      2% full length extension) with O6-meG at sites 1-4. Substitution of MnCl2 for
      MgCl2 in the reaction mixture greatly increased the bypass of O6-meG by Klenow
      fragment and DNA polymerase alpha but not Sequenase or DNA polymerase beta. The
      increased ability of Klenow fragment to bypass O6-meG in the presence of MnCl2
      was found to result from an increased incorporation of G (O6-meG at sites 1 and
      2) and A (O6-meG at sites 1, 2, and 3) opposite the lesion. The results indicate
      that O6-meG can block in vitro polymerization by several DNA polymerases and are
      consistent with the observed cytotoxic effects of methylating agents on mammalian
      cells.

PMID- 7634404
TI  - Exercise intensity dependent inhibition of 1-methyl-1-nitrosourea induced mammary
      carcinogenesis in female F-344 rats.
AB  - The objective of this experiment was to evaluate the effects of treadmill
      exercise on tumor induction in an experimental model for breast cancer. Female F
      344 rats were injected i.p. with 50 mg MNU/kg body wt at 50 and 57 days of age.
      Animals were assigned to one of five groups: sham exercise or 35% or 70% maximal
      treadmill running intensity for 20 or 40 min/day, 5 days per week. These work
      rates represent an exercise intensity level generally considered insufficient to
      improve cardiovascular fitness (35% maximal intensity) or an aerobic level of
      exercise sufficient to improve cardiovascular fitness in humans (70% maximal
      intensity). Rats were exercised for 3 months following carcinogen administration
      at which time the experiment was terminated. Mammary cancer incidence was reduced
      by as much as 37% and cancer multiplicity by < 60% at the highest exercise
      intensity. Unexpectedly, the degree of protection against cancer was proportional
      to the intensity but not to the duration of exercise.

PMID- 7634405
TI  - Treatment with chemopreventive agents, difluoromethylornithine and retinyl
      acetate, results in altered mammary extracellular matrix.
AB  - The effect of treatment with D-L-2-difluoromethylornithine (DFMO) plus retinyl
      acetate (RA) on the promotion stage of 1-methyl-1-nitrosourea (MNU)-induced
      mammary carcinogenesis was evaluated in female Sprague-Dawley rats. Combined
      treatment was more effective than single agent treatment in decreasing cancer
      incidence and multiplicity and in prolonging cancer latency. Increased efficacy
      was associated with reduced morphological complexity of the gland and increased
      mammary extracellular matrix. Using ovarian hormones to model mitogen stimulation
      in the mammary gland, DFMO plus RA treatment reduced mammary gland complexity in
      the absence of an effect on bromodeoxyuridine (BrDU) labeling index measured
      immunohistochemically. Morphological and biochemical evaluation of these glands
      revealed increased levels of extracellular matrix in rats treated with
      chemopreventive agents. Tenascin expression and fibronectin levels were elevated
      and laminin levels were decreased. The fact that matrix degrading proteinase
      activity was also increased indicated that tissue remodeling was modulated by
      these chemopreventive agents. These data provide evidence of alterations in
      epithelial cell-extracellular matrix interactions that could account in part for
      the chemopreventive effects of DFMO plus RA.

PMID- 7634406
TI  - Elevated 8-hydroxydeoxyguanosine in hepatic DNA of rats following exposure to
      peroxisome proliferators: relationship to mitochondrial alterations.
AB  - Recent studies have indicated a lack of correlation between hepatic 8-hydroxy-2'
      deoxyguanosine (8-OHdG) levels and the carcinogenicity of peroxisome
      proliferators (PP) and suggested that DNA in intact hepatic nuclei may be
      insensitive to increases in 8-OHdG resulting from PP exposure. The possibility
      that PP-induced elevations in acyl CoA oxidase (ACO) activity might result in
      oxidative damage to mitochondrial DNA (mtDNA) was therefore investigated by
      feeding male F344 rats the hepatocarcinogenic PP Wy-14,643 (Wy, 0.1% in the diet)
      for 3, 6, 11, or 22 weeks, or clofibric acid (CA, 0.5% in the diet) for 22 weeks.
      Following the respective PP exposures, hepatic peroxisomal acyl CoA oxidase
      activity was determined and DNA isolated from either mitochondria or
      unfractionated liver homogenates and analysed for the presence of 8-OHdG. PP
      treatment caused an increase in ACO activity (10- to 15-fold) at all time points
      examined and an increase of 8-OHdG (1.5- to 2-fold) in DNA isolated from
      unfractionated liver homogenates following PP treatment for 11 or 22 weeks. No
      increase of 8-OHdG in mtDNA was detected. However, quantitation of a PCR
      amplified region from the D-loop of mtDNA demonstrated a 2- to 3-fold increase in
      the relative amount of mtDNA in DNA isolated from unfractionated liver
      homogenates following 3, 11, and 22 weeks exposure to Wy or CA (22 weeks only).
      In addition, a slight increase in the mitochondrial volume density (1.4-fold) was
      observed in electron micrographs of liver samples from rats exposed to Wy for 22
      weeks. These results (i) demonstrate that PP treatment, at levels which cause an
      increase in ACO activity, does not cause oxidative damage to mtDNA, and (ii)
      suggest that one reason for the observed increase of 8-OHdG in DNA from
      unfractionated liver homogenates may be an increase in the amount of mtDNA
      present in these samples. Furthermore, these studies provide additional evidence
      against a role of oxidative DNA damage, measured as 8-OHdG, in PP-induced rodent
      hepatocarcinogenesis and suggest that alterations in mitochondria or other
      effects may be more pertinent to PP-related carcinogenesis.

PMID- 7634407
TI  - DNA adduct formation in the bone marrow of B6C3F1 mice treated with benzene.
AB  - We used P1-enhanced 32P-postlabeling to investigate DNA adduct formation in the
      bone marrow of B6C3F1 mice treated intraperitoneally with benzene (BZ). No
      adducts were detected in the bone marrow of controls or mice treated with various
      doses of BZ once a day. After twice-daily treatment with BZ, 440 mg/kg, for 1 to
      7 days, one major and two minor DNA adducts were detected. The relative adduct
      levels ranged from 0.06-1.46 x 10(-7). In vitro treatment of bone marrow from
      B6C3F1 mice with various doses of hydroquinone (HQ) for 24 h also produced three
      DNA adducts. These adducts were the same as those formed after in vivo treatment
      of bone marrow with BZ. Co-chromatography experiments indicated that the
      principal DNA adduct detected in the bone marrow of B6C3F1 mice was the same as
      that detected in HL-60 cells treated with HQ. This finding suggests that HQ may
      be the principal metabolite of BZ leading to DNA adduct formation in vivo. DNA
      adduct 2 corresponds to the DNA adduct formed in HL-60 cells treated with 1,2,4
      benzenetriol. DNA adduct 3 remains unidentified. After a 7-day treatment with BZ,
      440 mg/kg twice a day, the number of cells per femur decreased from 1.6 x 10(7)
      to 0.85 x 10(7), indicating myelotoxicity. In contrast, administration of BZ once
      a day produced only a small decrease in bone marrow cellularity. These studies
      demonstrate that metabolic activation of BZ leads to the formation of DNA adducts
      in the bone marrow. Further investigation is required to determine the role of
      DNA adducts and other forms of DNA damage in the myelotoxic effects of exposure
      to BZ.

PMID- 7634408
TI  - Butadiene monoxide and deoxyguanosine alkylation products at the N7-position.
AB  - 3,4-Epoxy-1-butene, an active metabolite of 1,3-butadiene, was reacted with
      guanosine, deoxyguanosine and calf thymus DNA. The products were isolated and
      positively identified using various spectroscopic techniques. Treatment of calf
      thymus-DNA with 3,4-epoxy-1-butene yielded two N7-guanine adducts of equal
      stability. Depurination by neutral hydrolysis showed that 7-(2-hydroxy-3-buten-1
      yl)guanine (compound I) was formed in greater quantities compared to its
      regioisomer 7-(1-hydroxy-3-buten-2-yl)guanine (compound II); spontaneous
      depurination experiments showed that compound I was released in the highest
      proportion. The circular dichroism spectral studies with R and S 3,4-epoxy-1
      butene revealed that the reaction mechanism at aqueous neutral pH media is more
      similar to SN2-type rather than SN1-type. The HPLC-electrochemical detection
      method used to carry out the DNA alkylation study provides a rapid and sensitive
      quantitation of N7 guanine adducts in biological fluids. This serves as a useful
      tool for further human biomonitoring experiments.

PMID- 7634409
TI  - Redox-active chalcogen-containing glutathione peroxidase mimetics and
      antioxidants inhibit tumour promoter-induced downregulation of gap junctional
      intercellular communication between WB-F344 liver epithelial cells.
AB  - Evidence is mounting supporting a role for oxidative stress in the mechanism of
      tumour promotion in response to agents such as 12-O-tetradecanoylphorbol-13
      acetate (TPA). In this paper we demonstrate that glutathione peroxidase-mimetic
      xenobiotics, ebselen, ebselen-glutathione, alpha-(phenylselenenyl) acetophenone
      and bis-(4-aminophenyl) telluride (at concentrations between 10 microM and 50
      microM) all demonstrate protective effects on TPA-induced downregulation of gap
      junctional intercellular communication (GJIC) between WB-F344 rat liver
      epithelial cells. These effects were, in each case, diminished if the cells were
      depleted of their intracellular glutathione, and potentiated if glutathione was
      supplemented into the incubations. Additionally, bis-(4-aminophenyl) selenide and
      several N-substituted analogues, possessing potent antioxidant activity but being
      devoid of GSH peroxidase-mimetic activity, demonstrated remedial activity against
      TPA-induced downregulation of GJIC. Structure-activity relationships between
      these molecules showed a strong correlation to the oxidation potential of the
      selenium atom in the compound as the bis-(4-nitrophenyl)- and bis-(4-cyanophenyl)
      derivatives, which possess poor antioxidant capacity and a half-wave redox
      potential well above +1.0 V, did not affect TPA-induced effects on GJIC.
      Examination of the mechanism of action of these redox-active compounds
      demonstrated correlations between their abilities to (i) prevent TPA-induced
      downregulation of GJIC, (ii) abolish the accumulation of intracellular oxidants
      and (iii) prevent the hyper-phosphorylation and internalization of connexin 43 in
      the cells. The active compounds were also able to prevent the rapid, TPA-induced
      translocation of protein kinase C to the particulate fraction of the cells,
      without affecting phorbol ester binding. These data support a synergistic role
      for oxidants and other TPA-dependent responses within the cell in mediating the
      downregulation of GJIC. Such oxidative metabolism may play a role in the control
      of translocation of protein kinase C from the cytosol to membranes in response to
      TPA within these cells. Despite the nature of the in vitro test system studied,
      the data also clarify the molecular basis for a potential anti-tumour promotive
      effect of antioxidants, based on established redox chemistries of several series
      of structurally-related molecules.

PMID- 7634410
TI  - Identification of clastogenic and/or aneugenic events during the preneoplastic
      stages of experimental rat hepatocarcinogenesis by fluorescence in situ
      hybridization.
AB  - A growing body of evidence from human and animal cancer cytogenetics studies
      indicates that aneuploidy is an important chromosome change in carcinogenesis. To
      understand the role of this genetic phenomenon during the first steps of an
      experimental cancer model, molecular and cellular techniques were combined. A
      sequential cytogenetic study of a modified Solt-Farber liver cancer model in the
      rat was performed to identify the importance of chromosome versus genome
      mutations. Male Wistar rats were initiated with diethylnitrosamine (DENA),
      followed by a 2-acetylaminofluorene exposure to select resistant hepatocytes.
      Chronic phenobarbital (PB) treatment was used to induce promotion. Cell
      proliferation was induced by a necrogenic dose of CCl4, administered during the
      selection period (Gerlans protocol) or 3 days before hepatocyte isolation
      (experimental protocol). In order to discriminate between genetic events causing
      chromosome breakage (clastogenic) and those that induce chromosome loss
      (aneugenic), isolated micronucleated hepatocytes (MNH) were analysed for the
      presence of a centromere in the micronucleus (MN). Non-radioactive in situ
      hybridization with a rat centromere satellite 1 DNA probe was applied. Our
      results show that the majority of the observed genetic changes, expressed as MN
      during different preneoplastic stages, were of clastogenic origin. However, the
      number of induced aneugenic hepatocytes increased markedly during the promotion
      period of the Gerlans protocol (approximately 7-fold above control) and during PB
      exposure in the experimental protocol (approximately 4-fold above control).
      Additionally, these stages were also characterized by an increased level of MN
      expression (20.3 < % MNH < 32.8), in comparison with the initiation stage after
      DENA exposure (13.5 < % MNH < 17.1). Although it is not yet clear if these
      genetic alterations have a causative nature in neoplastic liver transformation,
      the use of interphase cytogenetics certainly might lead to a better understanding
      of the genomic changes which occur during experimental hepatocarcinogenesis.

PMID- 7634411
TI  - Identification of 3 alpha-hydroxy-cyproterone acetate as a metabolite of
      cyproterone acetate in the bile of female rats and the potential of this and
      other already known or putative metabolites to form DNA adducts in vitro.
AB  - Cyproterone acetate (CPA) is a synthetic steroid hormone used in the therapy of
      prostate cancer in men and different forms of acne and hirsutism in women. CPA
      has been shown by 32P-postlabeling analysis to bind covalently to hepatic DNA of
      rats in vivo and in vitro. A prerequisite for DNA adduct formation of CPA is
      metabolic activation of the drug to a reactive intermediate. In the present study
      bile was collected from [3H]CPA-treated female rats and, following
      chromatographic separation of bile extracts, fractions of the eluate were
      examined for the presence of reactive metabolites which were able to form adducts
      with calf thymus DNA in vitro. The formation of adducts was detected by 32P
      postlabeling analysis. One major metabolite of CPA present in the bile extracts
      was isolated and, following a thorough structural elucidation by mass
      spectrometry and 1H-NMR, this metabolite was identified as 3 alpha-hydroxy
      cyproterone acetate (3 alpha-OH-CPA). This metabolite was able to form the same
      major adduct in vitro which has been observed before in CPA-treated rats in vivo
      and in rat hepatocytes in vitro. A number of already known or putative
      metabolites of CPA were available as authentic standards and these were also
      examined for their propensity to form adducts in vitro. A positive result was
      obtained for 3-O-acetyl-cyproterone acetate, which formed the same major adduct
      as 3 alpha-OH-CPA. However, the presence of this putative metabolite in rat bile
      could not be demonstrated. Besides 3 alpha-OH-CPA, additional reactive
      metabolites of CPA were present in the bile extracts, however, since these were
      only minor components, their chemical structures could not be elucidated.

PMID- 7634412
TI  - Inhibition of benzopyrene-induced forestomach tumors by field bean protease
      inhibitor(s).
AB  - Protease inhibitors (PIs), particularly the soybean-derived Bowman-Birk
      inhibitor, have proved to be powerful blockers of carcinogenesis in many in vitro
      and animal model systems. However, so far an ability of PIs to suppress gastric
      carcinogenesis has not been demonstrated, because of the anticipated 'hostile'
      acidic gastric environment for the PI to exert its action. We therefore examined
      the ability of a purified PI from the Indian legume the field bean (FBPI), when
      administered by gavage, to subdue benzopyrene (BP)-induced neoplasia of the
      forestomach of mice. Forestomach tumors were produced in female Swiss albino mice
      by oral administration of BP at a dose of 1 mg twice weekly for 4 weeks. Groups
      of mice were treated per os with an aqueous solution of FBPI for 3 months or more
      at a dose of 20 mg/kg once daily, six times a week, either from the initiation of
      carcinogenesis or after completion of the carcinogen treatment. Another group was
      treated likewise with autoclaved inactive FBPI. Mice of both the FBPI-treated
      groups showed statistically significant (P < 0.001) reductions in the
      multiplicity of gastric tumors, with the tumor incidence being unaffected.
      However, the suppression of tumor multiplicity was appreciably (P < 0.01) more in
      the group that received FBPI treatment concomitantly with the carcinogen. The
      mice that were treated with heat-inactivated FBPI showed similar tumor
      multiplicity to the BP-treated group, indicating that the oncopreventive activity
      of FBPI is related to its protease inhibitory capacity. These observations point
      to the potential of PIs as effective chemoprotectors against gastric cancer in
      animals and, possibly, in humans as well.

PMID- 7634414
TI  - Inhibition of c-Fos expression in the UV-irradiated epidermis by topical
      application of antisense oligodeoxynucleotides suppresses activation of
      proliferating cell nuclear antigen.
AB  - Induction of c-fos protooncogene expression following exposure of mammalian skin
      to UV irradiation suggests an involvement in UV-induced alterations of epidermal
      cell proliferation and viability. In the present study we have investigated
      whether topically administered c-fos antisense oligodeoxynucleotides (ODNs)
      inhibit c-fos activation in the UV-exposed rat skin and thereby modulate the
      delayed increase in cellular proliferative activity. The accumulation of c-Fos
      immunolabeled nuclei in the epidermis was almost completely blocked 18 h post
      irradiation by topical treatment with the c-fos antisense ODN. The co-expression
      of c-Jun was not affected and a random sequence control ODN was ineffective.
      Epicutaneous application of fluorescein-labeled ODNs revealed penetration into
      the underlying epidermis. The appearance of nuclear immunoreactivity for
      proliferating cell nuclear antigen (PCNA) 18 h after UV exposure was
      significantly suppressed in the epidermis treated with c-fos antisense ODNs. In
      vitro PCNA is involved in both DNA repair synthesis and DNA replication, and the
      expression of PCNA mRNA is increased after UV irradiation. Thus, it may be
      speculated that UV-induced c-Fos transcription factor may be linked to repair of
      photodamaged DNA and/or cell cycle progression by trans-activating PCNA gene
      expression.

PMID- 7634413
TI  - 32P-postlabelling determination of DNA adducts of malonaldehyde in humans: total
      white blood cells and breast tissue.
AB  - DNA adducts of malonaldehyde (MA) were measured in total white blood cells (TWBC)
      of healthy individuals from both sexes and different ages, as well as in breast
      tissue (BT) samples obtained from healthy females undergoing reduction
      mammaplasty. A large interindividual variation in adduct levels was observed. The
      average adduct level found in TWBC, considering both sexes and all ages was 2.6
      +/- 1.2 adducts/10(7) nucleotides (n = 26). A similar average DNA adduct
      concentration was found in BT and amounted to 3.0 +/- 1.3 (n = 7) adducts/10(7)
      nucleotides. Our results show that DNA adducts of MA can be measured in humans
      using 32P-postlabelling in combination with nuclease P1 and reversed-phase HPLC
      as adduct enrichment procedures, and further validate these adducts as suitable
      biomarkers for the measurement of DNA damage inflicted by endogenously induced
      oxidative processes such as lipid peroxidation.

PMID- 7634415
TI  - The methylation status of the gene for O6-methylguanine-DNA methyltransferase in
      human Mer+ and Mer- cells.
AB  - O6-Methylguanine-DNA methyltransferase (MGMT) plays an important role in
      protecting cells from the mutagenic potency of alkylating agents. This study
      addresses the role of DNA methylation in the expression of the human MGMT gene.
      Southern blot analysis of DNA from human Mer+ (MGMT proficient) and Mer- (MGMT
      deficient) cell lines demonstrated that the methylation state of a unique SmaI
      site in the MGMT gene promoter, previously shown by others to be invariably
      unmethylated in Mer+ cells and methylated in Mer- cells, did not correlate with
      the Mer phenotype. Neither was there any significant difference in the density of
      CpG methylation in the MGMT gene 5'-flanking sequences between Mer+ and Mer-
      cells. On the other hand, the body of the MGMT gene was less methylated in most
      Mer- cells relative to Mer+ cells, and in three of six Mer- cell lines the gene
      was essentially methylation-free. Interestingly, the Mer- cells that were
      hypomethylated in the MGMT gene also tended to be less methylated at other loci.
      Widespread hypomethylation is a frequent trait in carcinogenesis, and may be
      involved in development of the frequently found Mer- phenotype.

PMID- 7634417
TI  - Estradiol-17 beta as an initiation modifier for radiation-induced mammary
      tumorigenesis of rats ovariectomized before puberty.
AB  - This investigation evaluated the roles of estradiol-17 beta, progesterone and
      prolactin in the initiation of mammary tumorigenesis by irradiation. Sixty day
      old Wistar-MS rats ovariectomized bilaterally at 23 days of age were injected
      daily with olive oil, estradiol-3-benzoate (E2B), progesterone or haloperidol for
      14 days, and were then irradiated with gamma-rays (260 cGy) on the morning
      following the last injection. Diethylstilbestrol pellets were administered by
      implantation 30 days after the irradiation. Following treatment with E2B, the
      incidence of mammary tumors was increased 2.2-fold, in comparison with that in
      the corresponding control rats. Bilateral ovariectomy before puberty caused the
      mammary glands of adult rats to atrophy, and a low degree of differentiation with
      long narrow ducts was observed in whole mounts. The DNA synthesis in the mammary
      glands and serum prolactin level of E2B-treated rats were markedly increased and
      the terminal ducts showed distinctly increased differentiation into terminal end
      buds and alveolar buds with prolactin receptors. When progesterone, another
      ovarian hormone, or haloperidol, a dopamine antagonist in adenohypophysis, was
      injected into the rats under estrogen-free conditions, neither expression of
      prolactin receptors nor stimulation of DNA synthesis was observed in the mammary
      glands, and the incidence of mammary tumors induced by irradiation was lower than
      that observed in rats treated with E2B. Combined treatment with E2B and
      progesterone resulted in a reduction in the incidence of mammary tumors and in
      serum prolactin levels compared with those in E2B alone, in spite of the
      synergistic effects on prolactin receptor concentration and DNA synthesis by the
      two hormones. On the other hand, concurrent administration of haloperidol did not
      reduce the E2B-induced tumor incidence or prolactin concentration in serum. Many
      of the mammary tumors which developed in the ovariectomized rats were of the ER(
      )PgR(-) type. The incidence of development of ER(+)PgR(+) tumors was increased by
      treatment with E2B before the irradiation, and no ER(-)PgR(-) tumors were
      observed in this group. Our results suggest that estrogen is a direct or indirect
      sensitizer for tumor initiation by radiation, and is also one of the regulatory
      factors for hormone dependence of radiation-induced mammary tumors.

PMID- 7634416
TI  - The enhancing effect of fasting/refeeding on the growth of nodules selectable by
      the resistant hepatocyte model in rat liver.
AB  - Caloric restriction causes a generalized decrease in growth rate and has been
      shown to delay the development of both spontaneous and induced neoplasia. In
      contrast to chronic food restriction, the extreme condition of fasting/refeeding
      is associated with an overall increase in cell turnover in several organs,
      including liver, compared with regular feeding. The present study was therefore
      designed to investigate the effect of complete food withdrawal followed by
      refeeding on the growth of hepatocyte nodules in initiated rat liver. Male
      Fischer 344 rats were given a single dose of diethylnitrosamine (DEN, 200 mg/kg
      i.p.) and then, starting 1 wk later, they were exposed to one or three cycles of
      fasting (3 days) followed by refeeding (11 days). The control group was fed
      continuously. Seven weeks after DEN administration all rats were subjected to the
      resistant hepatocyte model (2-acetylaminofluorene coupled with CCl4) and 2 weeks
      later 2/3 partial hepatectomy (PH) was performed. All animals were killed 2 weeks
      after surgery. At PH rats given one cycle of fasting/refeeding had significantly
      larger glutathione S-transferase 7-7-positive hepatic lesions compared with
      controls (mean area 0.73 +/- 0.04 versus 0.50 +/- 0.05 mm2, P < 0.025; mean
      percent area 25.6 +/- 3.2 versus 12.4 +/- 0.9, P < 0.005), while no significant
      change was observed in their number. The observed differences were more
      pronounced with three cycles of fasting/refeeding. A similar pattern of results
      was obtained at the time of killing. It is concluded that fasting/refeeding can
      exert a positive effect on the growth of rat hepatocyte foci and nodules, in
      contrast to the general inhibitory effect on carcinogenesis caused by food
      restriction.

PMID- 7634418
TI  - Characterization of macromolecular lignins as Epstein-Barr virus inducer in
      foodstuff associated with nasopharyngeal carcinoma risk.
AB  - Epstein-Barr virus (EBV)-inducing activity was previously demonstrated to occur
      in various foodstuffs, including dried salted fish in southern China and
      'harissa', a homemade spice mixture in Tunisia, whose consumption is
      epidemiologically associated with an increased risk for developing nasopharyngeal
      carcinoma (NPC). For the isolation and the characterization of active ingredients
      in harissa, we used as a rapid screening assay the induction of the
      chloramphenicol acetyltransferase (CAT) activity through the EBV-DR promoter in
      DR-CAT Raji cells. After fractionation of harissa and column chromatography on
      Sepharose-CL4B, the major inducing activity was associated with a macromolecular
      fraction which was chemically characterized as liginin-containing complexes. The
      active material enhanced EBV-DR induction with an activity comparable to the
      tumor promoter and strong EBV inducer, 12-O-tetradecanoylphorbol-13-acetate.
      Experiments with inhibitors of protein kinase C-related pathways suggested that
      the EBV-inducing activity of lignin fractions operates through a different
      pathway. Our results on the presence of specific lignin fractions in high-risk
      food items that can induce important cellular functions linked to tumor promotion
      are discussed in relation to NPC genesis and etiology.

PMID- 7634419
TI  - Improvement in the efficiency of the in vitro transformation assay method using
      BALB/3T3 A31-1-1 cells.
AB  - In order to improve the in vitro transformation assay using BALB/3T3 cells, which
      is routinely conducted with minimal essential medium (MEM) containing 10% fetal
      calf serum (FCS), we examined the effect of a new medium after the cells had been
      treated with carcinogens. Preliminary experiments suggested that the use of T
      medium (modified DME/F-12) supplemented with insulin, transferrin, ethanolamine
      and sodium selenite plus 2% FCS resulted in a high transformation frequency. The
      present study confirmed that this medium was very efficient at inducing
      transformation foci. Transformation frequency was highest when 12-O
      tetradecanoylphorbol-13-acetate (TPA) was started from 1 week after the
      carcinogen treatment. According to the new protocol using this medium, the
      transformation frequency was five times higher and transformation foci appeared
      much earlier than with the protocol using usual MEM plus 10% FCS medium. In
      addition, we tested several typical carcinogens and a promoter in order to
      confirm the applicability of the new protocol to the two-stage transformation
      assay. N-Methyl-N'-nitro-N-nitro-soguanidine (MNNG) and benzo[a]pyrene, but not
      noncarcinogenic benzo[e]pyrene, induced transformation foci. In the metabolic
      activation system dimethylnitrosamine gave a highly positive transformation.
      Okadaic acid, a non-TPA-type tumor promoter, enhanced transformation of MNNG
      initiated cells. These studies demonstrate that the use of the proposed medium
      drastically improves transformation frequency in the two-stage in vitro
      transformation assay.

PMID- 7634420
TI  - A monoclonal antibody that recognizes alkali-stabilized melphalan-DNA adducts and
      its application in immunofluorescence microscopy.
AB  - Monoclonal antibodies were produced that recognized alkali-stabilized
      modifications of DNA formed by the anticancer drug melphalan in order to permit
      measurement of melphalan-DNA adducts in individual cells by immunofluorescent
      staining. Antibody Amp4/42 did not bind to alkali-treated control DNA or to DNA
      that had been alkylated with melphalan but not exposed to alkali. In a
      competitive enzyme-linked immunoadsorbent assay using DNA that had been reacted
      with radioactive melphalan in simple solution a 50% reduction in assay signal was
      caused by approximately 100 fmol total melphalan-DNA adducts/assay well. This
      sensitivity was only slightly influenced by heat denaturation of the DNA before
      alkylation or by the frequency of alkylated sites on DNA. The heat stability of
      the adducts recognized by Amp4/42 was greatly increased by the alkali-induced
      change which, in 0.1 M NaOH at 37 degrees C, was complete by 30 min. Amp4/42
      appears to recognize a ring-opened structure resulting from alkaline hydrolysis
      of 7-alkyldeoxyguanosine. Melphalan-DNA adducts formed in mammalian cells showed
      an alkali-induced increase in immunoreactivity which occurred at a similar rate
      to that seen in DNA that had been alkylated in simple solution, but their maximum
      overall immunoreactivity was approximately 10-fold lower. This indicated that in
      cells the adducts recognized by Amp4/42 were formed or persisted as a smaller
      proportion of total adducts compared with alkylation of pre-purified DNA in
      simple solution. This antibody permitted immunofluorescent detection of melphalan
      DNA adducts in single cells.

PMID- 7634421
TI  - Inhibition of oral carcinogenesis by the arotinoid mofarotene (Ro 40-8757) in
      male F344 rats.
AB  - The chemopreventive effect of dietary administration of a new arotinoid,
      mofarotene (Ro 40-8757), which contains a morpholine structure in the polar end
      group, during the initiation phase of 4-nitroquinoline 1-oxide (4-NQO)-induced
      oral carcinogenesis was investigated in male F344 rats. Also, modulatory effects
      of this compound on polyamine levels (biomarkers of proliferation), the 5
      bromodeoxyuridine-labeling index and the number of silver stained nucleolar
      organizer region proteins (AgNORs)/nucleus were assessed in the target
      epithelium. Rats were fed Ro 40-8757 at concentrations of 250 and 500 p.p.m. for
      10 weeks. One week after the commencement of the diets, 4-NQO (20 p.p.m.) was
      administered in the drinking water for 8 weeks. Feeding of Ro 40-8757 at both
      doses caused a 78% reduction in the incidence of tongue neoplasms (squamous cell
      papilloma and carcinoma) by 32 weeks when compared with rats treated with 4-NQO
      alone (P < 0.05). Similarly, in rats treated with 4-NQO together with Ro 40-8757
      the incidence of preneoplastic lesions (hyperplasia and dysplasia) was
      significantly less than the 4-NQO alone group (P < 0.05). Expression of three
      biomarkers was also decreased significantly by dietary treatment with Ro 40-8757.
      Thus a new arotinoid, Ro 40-8757, inhibited the oral carcinogenesis induced by 4
      NQO when it was administered concurrently with the carcinogen. These results
      might suggest the possible application of Ro 40-8757 for cancer chemoprevention
      in the oral cavity, in addition to the breast.

PMID- 7634422
TI  - Methylene chloride-induced DNA damage: an interspecies comparison.
AB  - DNA single-strand (ss) breaks were detected in the livers of B6C3F1 mice
      immediately following exposure to 4000-8000 p.p.m. methylene chloride (MC) for 6
      h. This damage was undetectable 2 h after exposure, suggesting an active DNA
      repair process. Similarly, DNA ss breaks were detected in whole lung homogenates
      taken from mice exposed to 2000-6000 p.p.m. MC. The DNA of mouse Clara cells
      incubated in vitro with MC was also damaged at concentrations of 5 mM MC and
      above. Pre-treatment of mice with the glutathione depletor buthionine
      sulphoximine (BSO) caused a decrease in the amount of DNA damage detected,
      suggesting a GST-mediated mechanism. DNA damage was also reduced in Clara cells
      when incubated in vitro with MC in the presence of BSO. In CHO cells induction of
      DNA damage was dependent upon exogenous MC metabolism by mouse liver S100
      fraction (but not microsomes) in the presence of GSH. DNA ss breaks were not
      induced by MC in hamster hepatocytes in vitro at concentrations from 5 to 90 mM
      MC, nor in eight individual samples of normal human hepatocytes exposed to MC at
      similar concentrations. The ability of MC to induce DNA ss breaks in the four
      species studied is entirely compatible with the known carcinogenicity of this
      chemical in animals and offers experimental evidence to suggest that humans would
      not be susceptible to MC-induced liver cancer. The DNA ss breaks correlate with
      the metabolism of MC by the GST pathway and provide an explanation for the lack
      of sensitivity of hamsters and rats to MC-induced liver cancer.

PMID- 7634423
TI  - Effect of Helicobacter mustelae infection on ferret gastric epithelial cell
      proliferation.
AB  - The effect of Helicobacter mustelae infection on gastric epithelial proliferation
      was studied in ferrets colonized with H.mustelae and specific pathogen-free (SPF)
      ferrets not infected with H.mustelae. Thirteen H. mustelae-infected ferrets
      between the ages of 13 and 32 months and 16 SPF ferrets between 6 and 18 months
      were analyzed. Bacterial cultures, urease tests and Warthin-Starry stains were
      used to identify H.mustelae. Tissues obtained from the antrum and the body
      regions of the stomach were assayed by proliferating cell nuclear antigen (PCNA)
      immunohistochemistry and measured using a computerized color image analysis
      system. PCNA-expressing gastric epithelia in the antrum and the body regions were
      significantly increased in the H.mustelae-infected ferrets versus the SPF ferrets
      (P < 0.001). PCNA positivity in the antrum regions of both the H.mustelae
      infected ferrets and SPF ferrets was significantly higher than that of the body
      regions (P < 0.001). Comparison of the histopathology of infected ferrets
      indicated that PCNA positivity correlated with the histological severity of
      gastritis. This study suggests that cell proliferation in ferret gastric mucosa
      increases with H.mustelae infection and provides evidence that PCNA is a useful
      biomarker for studying the changes in cell kinetics in the ferret stomach. The
      data also further support the use of the H.mustelae-infected ferret as an animal
      model for studying the pathogenesis of Helicobacter pylori-induced gastric
      diseases of humans.

PMID- 7634424
TI  - DNA mismatch repair mutants do not increase N-methyl-N'-nitro-N-nitrosoguanidine
      tolerance in O6-methylguanine DNA methyltransferase-deficient yeast cells.
AB  - Treatment of cells with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) produces,
      among other lesions, mutagenic and carcinogenic lesions such as O6-methylguanine
      (O6MeG) and O4-methylthymine in DNA. An O6MeG DNA methyl-transferase (MTase)
      specifically and efficiently repairs such lesions. MTase-deficient bacterial,
      yeast and mammalian cells exhibit increased sensitivity not only to MNNG-induced
      mutagenesis, but also to MNNG-induced killing, suggesting that O6MeG-type lesions
      are also lethal to the cells. The lethal effect caused by O6MeG is not clear.
      Results from several recent experiments indicate that some MNNG-tolerant cell
      lines exhibit a loss of DNA mismatch binding/repair activity, suggesting that
      functional mismatch repair is probably responsible for the cellular sensitivity
      to DNA methylating agents. We tested this abortive O6MeG-T mismatch repair
      hypothesis in a well-defined lower eukaryote, Saccharomyces cerevisiae. We found
      that while mgt1-deleted MTase-deficient yeast strains are hypersensitive to MNNG
      induced killing, combination of this mutation with any of the mlh1, msh2 or pms1
      mutations did not render cells more tolerant to killing. msh3 mutation also did
      not rescue MNNG-induced genotoxicity. Furthermore, through the isolation and
      characterization of MNNG-tolerant cell lines from the MTase-deficient mutants we
      demonstrated that a DNA mismatch repair defect is neither sufficient nor required
      for this process. Since both DNA repair MTases and mismatch repair proteins are
      highly conserved between yeast and mammalian cells, our results could suggest
      alternative mechanisms in the cellular tolerance to O6MeG-induced killing.

PMID- 7634425
TI  - Induction by estrogens of lipid peroxidation and lipid peroxide-derived
      malonaldehyde-DNA adducts in male Syrian hamsters: role of lipid peroxidation in
      estrogen-induced kidney carcinogenesis.
AB  - Estrogen-induced kidney carcinogenesis in male Syrian hamsters has previously
      been postulated to be mediated by free radicals generated by redox cycling of
      catecholestrogen metabolites. As part of our examination of this hypothesis, we
      have studied the induction of lipid peroxidation and lipid peroxide-derived
      malondialdehyde (MDA)-DNA adducts in kidney and liver of hamsters treated with
      single injections of diethylstilbestrol (DES) or with estradiol (E2) implants for
      various lengths of time. Treatment of hamsters with 50 and 100 mg/kg DES
      increased concentrations of both lipid hydroperoxides and of MDA-DNA adducts. In
      hamsters treated with E2 implants for up to 50 days, lipid peroxide levels in
      liver were double control values 3 h after hormone implantation, and then
      decreased to plateau values of 30% over controls. Those in kidney rose to 2- to 3
      fold above controls 3 days after hormone implantation and then decreased to
      plateau values of 51% above controls. MDA-DNA adduct levels were two or three
      times higher than those of controls in liver and kidney of hamsters treated with
      hormone implants for 3 and 7 days. Renal lipid peroxide concentrations were
      raised by chronic treatment with E2, but not by weakly carcinogenic estrogens
      ethinylestradiol or 2-fluoroestradiol. In contrast, MDA-DNA adduct levels were
      raised by all three steroidal estrogens 3 days after estrogen implantation. The
      increases in lipid peroxides and in MDA-DNA adducts in estrogen-treated hamsters
      support a mechanism of carcinogenesis by free radical generation via redox
      cycling of catcholestrogen metabolites. Lipid peroxides are postulated to play a
      dual role in estrogen-induced carcinogenesis, (i) as cofactors for cytochrome
      P450-mediated formation of catecholestrogen metabolites and their redox cycling,
      and (ii) as precursors of MDA, a DNA adduct-forming endogenous electrophile.

PMID- 7634426
TI  - Genetic susceptibility to papilloma progression in SENCAR mice.
AB  - Previous results showed that in an inbred line (SSIN) derived from outbred SENCAR
      mice there is a dissociation between susceptibility to papilloma development and
      the malignant conversion of these into squamous cell carcinomas (SCC). To extend
      this conclusion, we designed an interstrain breeding experiment using the two
      step carcinogenesis protocol in order to study the susceptibility to tumor
      progression of F1 offspring. The strains used were SSIN, BALB/c, both known for
      their resistance to papilloma progression, and SENCAR. Both the SSIN X SENCAR and
      SENCAR X SSIN F1s showed a promotion sensitivity similar to that of the SSIN
      mice. This behavior was also seen in the SSIN X (SSIN X SENCAR) and SSIN X
      (SENCAR X SSIN) backcrossed animals, suggesting that susceptibility to 12-O
      tetradecanoylphorbol-13-acetate promotion under these protocol conditions is
      inherited as a dominant trait. The BALB/c X SENCAR F1s showed an average response
      that was intermediate between the two parental strains/stocks. Regarding the
      progression, all F1s showed a cumulative number of SCCs similar to the SENCAR
      progenitor. We also investigated the previously described switch of keratin 1 to
      13 as a marker of premalignant progression, which is significatively delayed in
      SSIN mice compared with SENCAR mice. The SSIN X SENCAR F1s expressed this switch
      in a way similar to the SENCAR mice. These findings suggest that susceptibility
      to tumor progression is inherited as a dominant autosomal trait. The putative
      gene(s) that confers susceptibility is present in the SENCAR stock and was
      probably lost in the selection and inbreeding of the SSIN mice.

PMID- 7634427
TI  - Estrone-induced cell proliferation and differentiation in the mammary gland of
      the female Noble rat.
AB  - In this study we examined the influence of estrone on proliferation and
      differentiation in the mammary gland of female Noble rats. Estrone treatment
      increased proliferation in mammary epithelial cells at days 3 and 7, and peaked
      by day 11 of estrone exposure. In addition, estrone exposure altered cell cycle
      kinetics. Animals exposed to estrone for 11 days demonstrated a 9-fold increase
      in the cells in G1 phase and a 48-fold increase in the cells in S phase, compared
      to those of controls. Differentiation, measured by the degree of lobular
      maturation, was significantly increased in the treatment group by day 7 and
      continued to mature through day 21 post estrone implant. The appearance of the
      mammary glands in these animals approached the morphology normally found during
      pregnancy and lactation. In a subset of animals we examined the effects of a
      concurrent treatment with luteolin, a bioflavonoid which has been shown to
      inhibit estrone binding to type II estrogen receptors. Luteolin significantly
      reversed the effects of estrone treatment on both proliferation and
      differentiation in these animals. Changes in proliferation and cell cycle
      kinetics have been shown to lead to genetic instability, ultimately resulting in
      cell transformation. Our results indicated an increase in proliferative cells by
      > 2-fold and a perturbation in cell cycle kinetics from estrone exposure. These
      changes may play a role in the induction of estrone-induced mammary cancer in the
      Noble rat model. In addition, the anti-proliferative action of luteolin suggests
      that it may play a protective role in estrone-induced mammary carcinogenesis.

PMID- 7634428
TI  - Mammary carcinogenicity in female CD rats of fjord region diol epoxides of
      benzo[c]phenanthrene, benzo[g]chrysene and dibenzo[a,l]pyrene.
AB  - We compared the mammary carcinogenicity in female CD rats of three fjord region
      diol epoxides to test our hypothesis that such sterically hindered molecules
      would be potent carcinogens. The diol epoxides tested were racemic anti-3,4
      dihydroxy-1,2-epoxy-1,2,3,4-tetrahydrobenzo[c]phenanthrene (BcPDE), anti-11,12
      dihydroxy-13,14-epoxy-11,12,13,14-tetrahydrobenzo[g]chrysene (BgCDE) and anti
      11,12-dihydroxy-13,14-epoxy-11,12,13,14-tetrahydrodibenzo[a,l ]pyrene
      (DB[a,l]PDE). Each diol epoxide was dissolved in dimethylsulfoxide (DMSO) and
      injected under the six nipples on the left side of the rat, with DMSO only being
      injected under the nipples on the right side. The total dose of each diol epoxide
      was 1.2 mumol/rat and there were 20 rats/group. The experiment was terminated 41
      weeks after treatment. All three diol epoxides were potent mammary carcinogens,
      with activity greater than previously observed for a bay region diol epoxide,
      anti-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE).
      DB[a,l]PDE induced tumors most rapidly, followed by BcPDE and BgCDE. However,
      different types of tumors were induced. For induction of adenomas and
      adenocarcinomas, BcPDE and BgCDE had comparable potency; both were more active
      than DB[a,l]PDE. In contrast, for induction of sarcomas, DB[a,l]PDE was
      significantly more active than BcPDE and BgCDE. The results of this study support
      our hypothesis that sterically hindered fjord region diol epoxides are potent
      mammary carcinogens in the rat.

PMID- 7634429
TI  - Inositol hexaphosphate inhibits growth and induces differentiation of PC-3 human
      prostate cancer cells.
AB  - We investigated the effects of inositol hexaphosphate (InsP6) on growth
      inhibition and differentiation of human prostate cancer cells PC-3 in vitro. A
      significant dose- and time-dependent growth inhibition was observed as tested by
      the MTT-incorporation assay (P < 0.05 at 1 mM InsP6 after 24 h treatment, P <
      0.01 at 0.1 mM after 3 days). DNA synthesis as determined by [3H]thymidine
      incorporation assay was also suppressed by InsP6 in a dose-dependent manner,
      occurring as early as 3 h after treatment and continuing up to 48 h (P < 0.01 at
      1 mM InsP6). A 9- to 10-fold increase (P < 0.01) in expression of HLA class I
      molecule associated with tumor immunosurveillance and cell differentiation was
      induced by InsP6. The marker for prostatic cell differentiation, prostate acid
      phosphatase, was significantly (P < 0.05) increased after 48 h treatment at 0.5-5
      mM InsP6. Since InsP6 strongly inhibits growth and induces differentiation in
      human prostate cancer cells in vitro, in vivo studies using a tumor xenograft
      model and a prostate carcinogenesis model are warranted to validate the efficacy
      of InsP6 in the treatment and prevention of prostate cancer.

PMID- 7634430
TI  - Non-random deletions at the dihydrofolate reductase locus of Chinese hamster
      ovary cells induced by alpha-particles simulating radon.
AB  - This study presents the physical characterization of mutants induced in mammalian
      cells by high linear energy transfer alpha-particle radiation that simulates
      exposure to radon daughters. Alpha-Particles from accelerated 4He at 150
      keV/microns were used to induce 20 Chinese hamster ovary mutants that are
      deficient in dihydrofolate reductase (DHFR) activity. Parental cells were the
      hemizygous UA21 line. Cell survival decreased exponentially in response to
      radiation dose from 0.25 to 1.75 Gy. Mutants were obtained at 1.0 (17/20) and
      1.25 Gy (3/20); treatments at 1.50 Gy failed to yield mutants. The induced
      frequency of mutation was 2.3 x 10(-6) at the 1.0 Gy dose, approximately 18-fold
      greater than the spontaneous mutation rate at this locus. DNA of the 20 confirmed
      null mutants were examined for alterations in the 25 kb DHFR gene by Southern
      blotting using a mixed probe that scans a continuous 34 kb of sequence. Deletions
      were the most prevalent induced change (18/20). Of the two point mutants, DNA
      sequencing showed that one carries a T:A-->G:C base substitution that changed
      Val135 to Gly in exon 5; carcinogen-induced reversion to a DHFR+ phenotype at a
      frequency of 3 x 10(-6) confirmed that the other also carried a single base
      change. The distribution of deletion break sites in the DHFR locus was non
      random. In half of the mutants deletion break sites were clustered within a
      single 9.4 kb DHFR intron. Fine mapping within the gene of 14 mutants by Southern
      blotting localized 10 distinct break sites to small restriction fragments (< 2
      kb). Results of this mapping indicated that three unequivocally independent
      mutants apparently arose by the same deletion and that others shared single break
      sites. Deletion sizes in these mutants were determined by Southern analysis using
      six cosmids and two plasmid probes that together span approximately 500 kb of
      sequence in the region of the DHFR locus. Probing blots with the cosmids defined
      a maximal deletion size in 15/17 mutants and confirmed that deletions extended <
      150 kb in 11, a qualitatively different result from that previously obtained
      after a similar analysis of gamma-ray-induced DHFR- mutants. Since deletions were
      non-randomly distributed, typically less than replicon size and spared regions
      containing matrix attachment sites, the results suggest a model whereby alpha
      particles induce double-strand breaks in accessible chromatin loops.

PMID- 7634431
TI  - The Hcr (hepatocarcinogen resistance) loci of DBA/2J mice partially suppress
      phenotypic expression of the Hcs (hepatocarcinogen sensitivity) loci of C3H/HeJ
      mice.
AB  - Both male DBA/2J and C3H/HeJ mice are highly susceptible to hepatocarcinogenesis
      induced by experimental treatment with N,N-diethylnitrosamine (DEN) relative to
      male C57BL/6J mice. While C3H/HeJ mice carry multiple sensitivity loci,
      designated Hcs (hepatocarcinogen sensitivity), our previous study indicated that
      the susceptibility of DBA/2J mice results from the combined effects of multiple
      sensitivity loci and two major resistance loci, Hcr-1 and -2 (hepatocarcinogen
      resistance). We proposed that BXD-15 recombinant inbred mice, which are extremely
      resistant to DEN-induced hepatocarcinogenesis, may carry the Hcr loci from the
      parental DBA/2J mice, but few, if any, of the multiple sensitivity loci.
      Conversely, the extremely sensitive BXD-11 recombinant inbred mice may carry most
      of the multiple sensitivity loci of the DBA/2J parents, but neither of the major
      resistance loci. In order to confirm our genetic model for hepatocarcinogenesis
      in DBA/2J mice and to evaluate the phenotypic effects of the Hcr loci on the Hcs
      loci of C3H/HeJ mice, we characterized hepatocarcinogen sensitivities of F1 mice
      generated from the crosses involving BXD-11, BXD-15, C3H/HeJ and C57BL/6J
      strains. When male mice were initiated with DEN at 12 days of age and liver
      tumors were enumerated at 32 weeks of age, (BXD-15 x BXD-11)F1 mice had one sixth
      the number of liver tumors observed in (C57BL/6J x BXD-11)F1 mice, consistent
      with our previous conclusion that DBA/2J mice possess hepatocarcinogen resistance
      genes in spite of their high susceptibility to DEN. Significantly, (C57BL/6J x
      C3H/HeJ)F1 mice also had a 2.3-fold greater number of liver tumors and 5.5-fold
      higher total volume of initiated lesions per liver as compared with (BXD-15 x
      C3H/HeJ)F1 mice, indicating that the hepatocarcinogen resistance genes inherited
      by BXD-15 mice are capable of suppressing the Hcs phenotype. Thus the Hcr loci
      may influence a wide variety of hepatocarcinogen sensitivity loci and be able to
      act as general resistance loci for chemical hepatocarcinogenesis. Stereological
      analysis of initiated hepatocellular lesions with glucose 6-phosphatase
      deficiency revealed that the resistance genes largely influence the promotion
      stage of hepatocarcinogenesis.

PMID- 7634432
TI  - The synergism between bovine papillomavirus type 4 and quercetin is dependent on
      the timing of exposure.
AB  - Exposure to the flavonoid quercetin and transfection with bovine papillomavirus
      type 4 (BPV-4) DNA lead to oncogenic transformation of primary bovine cells. Here
      we show that the synergism between quercetin and BPV-4 (or its E7 oncogene) is
      stronger the shorter the interval between the two treatments. Quercetin
      immortalizes transformed cells, confers anchorage-independent growth and induces
      tumorigenicity in cells transfected only with the E7 oncogene.

PMID- 7634433
TI  - Glutathione S-transferase GSTM1 null genotype is not overrepresented in
      Australian patients with nevoid basal cell carcinoma syndrome or sporadic
      melanoma.
AB  - The GSTM1 gene on chromosome 1p encodes the carcinogen-detoxification enzyme,
      glutathione S-transferase (mu subclass). The homozygous null genotype at this
      locus has been associated with increased susceptibility to malignancy, including
      some skin cancers. One hundred and twenty-four Australian patients with sporadic
      melanoma and 62 with familial basal cell carcinomas (a feature of nevoid basal
      cell carcinoma syndrome, NBCCS) were examined for germline homozygous deletions
      of GSTM1 using multiplex polymerase chain reactions. The homozygous null genotype
      was not overrepresented in either those with a single melanoma or in the NBCCS
      cases. Nor did it significantly accelerate tumorigenesis in either group.
      Analyses of much larger sample sizes will be required to investigate the
      representation of the null genotype in patients with multiple melanoma primaries
      and in those with melanoma co-existing with other non-cutaneous malignancies.

PMID- 7634434
TI  - Cardiac function in mice overexpressing the beta-adrenergic receptor kinase or a
      beta ARK inhibitor.

PMID- 7634435
TI  - Increased NIH funding no longer sacrosanct.

PMID- 7634436
TI  - Enhancing minority participation in research. The NHLBI experience.

PMID- 7634437
TI  - T-cells and T-cell clones in rheumatic fever valvulitis. Getting to the heart of
      the matter?

PMID- 7634438
TI  - Congenital AV block. Pace me now or pace me later?

PMID- 7634439
TI  - Elevation of circulating and ventricular adrenomedullin in human congestive heart
      failure.
AB  - BACKGROUND: Adrenomedullin (ADM) is a newly discovered vasodilating and
      natriuretic peptide that may play an important role in cardiorenal regulation.
      Although ADM was originally isolated from human pheochromocytoma, ADM-like
      immunoreactivity has also been widely detected in various tissues, including the
      cardiovascular system. METHODS AND RESULTS: In view of reports that ADM
      circulates in the body and that ADM gene and ADM-like immunoreactivity are
      present in the heart, the present study was designed to determine the plasma
      concentration of ADM in healthy subjects and in patients with congestive heart
      failure (CHF) and to investigate the immunohistochemical presence and
      localization of ADM in normal and failing human hearts. Plasma ADM concentration
      was 13.2 +/- 2.3 pg/mL in healthy subjects (n = 11) and increased to 47.3 +/- 6.7
      pg/mL in patients with CHF (n = 11 P < .05 versus normal). Human cardiac tissues
      were obtained from five patients with end-stage CHF undergoing cardiac
      transplantation. Five normal donor hearts that were used for cardiac
      transplantation served as sources for normal atrial tissues. Normal ventricular
      myocardium was also obtained by endomyocardial biopsy from the right ventricles
      of these donor hearts immediately before cardiac transplantation. Positive
      immunostaining was detected within the myocardia in both atria and ventricles of
      healthy and severely failing human transplanted hearts and was more intense in
      the atria than in the ventricles. Although there were no significant differences
      in the intensity of immunoreactivity between normal and failing atria, ADM
      immunoreactivity was significantly more intense in the ventricular myocytes from
      failing hearts compared with normal hearts. CONCLUSIONS: The present study
      demonstrates that plasma concentration of ADM is increased in patients with CHF
      and that ADM is present in the human heart. ADM immunoreactivity is markedly
      increased in the failing human ventricle, suggesting that ventricular ADM
      expression may be influenced by the circumstances associated with CHF. This
      supports a potential role for this newly identified vasoactive and natriuretic
      peptide, ADM, in the neurohumoral activation that characterizes human CHF.

PMID- 7634440
TI  - Coronary artery disease in heterozygous familial hypercholesterolemia patients
      with the same LDL receptor gene mutation.
AB  - BACKGROUND: Familial hypercholesterolemia (FH), an autosomal codominant disease,
      is characterized by high levels of LDL cholesterol and a high incidence of
      coronary artery disease (CAD). To date, genetic heterogeneity has hindered the
      proper assessment of the relation between risk factors and CAD in FH patients.
      METHODS AND RESULTS: We studied the association between CAD and common risk
      factors in a sample of 263 French Canadian FH patients (147 women, 116 men)
      carrying the same > 10-kb deletion of the LDL receptor gene. Thirty-five women
      and 54 men had CAD. The mean age of onset of CAD was 45.6 +/- 12.7 years in women
      and 38.8 +/- 9.4 years in men. Multiple logistic regression analyses were
      performed to test the association between CAD and age, tendon xanthomas,
      cigarette smoking, hypertension, diabetes mellitus, apolipoprotein E
      polymorphism, total plasma cholesterol, triglycerides, VLDL cholesterol, LDL
      cholesterol, HDL cholesterol, and lipoprotein(a) [Lp(a)]. In FH women,
      significant multivariate predictors were age (odds ratio, 1.10 for 1 year; P <
      .0001), VLDL cholesterol (odds ratio, 3.85 for 1 natural log unit; P < .002), and
      LDL cholesterol (odds ratio, 1.42 for 1 mmol/L; P < .02). In FH men, age (odds
      ratio, 1.08 for 1 year; P < .0001) and HDL cholesterol (odds ratio, 0.14 for 1
      mmol/L; P = .05) were significant predictors of disease. Lp(a) was not a
      significant predictor in univariate or multivariate analyses. CONCLUSIONS: This
      study suggests that increased risk of CAD in FH is not solely due to elevated LDL
      cholesterol levels and demonstrates a sex-specific lipoprotein influence on CAD
      in a large sample of FH patients carrying the same LDL receptor gene defect.

PMID- 7634441
TI  - Relation between the deletion polymorphism of the angiotensin-converting enzyme
      gene and late luminal narrowing after coronary angioplasty.
AB  - BACKGROUND: The insertion/deletion (I/D) polymorphism of the angiotensin
      converting enzyme (ACE) gene has been implicated in the pathogenesis of coronary
      artery disease. The deletion allele is strongly associated with the level of
      circulating ACE and is a potent risk factor for myocardial infarction. Recently,
      the deletion allele was also associated with the occurrence of visually diagnosed
      restenosis after percutaneous transluminal coronary angioplasty (PTCA) in a
      selected population of patients with acute myocardial infarction. METHODS AND
      RESULTS: We investigated the influence of the ACE I/D polymorphism on the
      occurrence of restenosis after PTCA with the use of quantitative coronary
      angiography. ACE I/D genotypes were characterized in 118 consecutive patients who
      had one-vessel disease and were undergoing systematic angiographic follow-up.
      Coronary angiograms were analyzed before and after PTCA and at follow-up (7.4 +/-
      3.0 months). Before PTCA, there were no clinical or angiographic differences
      among the three groups of genotypes (DD, n = 39; ID, n = 62; II, n = 17). After
      PTCA, the mean differences in minimal luminal diameter between post-PTCA and pre
      PTCA angiograms (acute gain) were identical in the three groups, as was the mean
      percent residual stenosis. At follow-up angiography, the mean difference in
      minimal coronary luminal diameter between post-PTCA and follow-up angiograms
      (late loss) was not significantly different in the three groups of genotypes. The
      percentage of patients with restenosis defined as a > 50% stenosis was identical
      in the three groups. CONCLUSIONS: In this quantitative study, the I/D
      polymorphism of the ACE gene had no influence on the occurrence of restenosis
      after coronary angioplasty.

PMID- 7634442
TI  - Association of left ventricular remodeling and nonuniform electrical recovery
      expressed by nondipolar QRST integral map patterns in survivors of a first
      anterior myocardial infarction. Captopril and Thrombolysis Study Investigators.
AB  - BACKGROUND: Progressive left ventricular dilatation after myocardial infarction
      is associated with a high mortality rate, the majority of which is arrhythmogenic
      in origin. The underlying mechanism of this relation remains unknown. It has been
      suggested, however, that left ventricular dilatation is accompanied by changes in
      repolarization characteristics that may facilitate the occurrence of life
      threatening ventricular arrhythmias. METHODS AND RESULTS: We examined 62-lead
      body surface QRST integral maps during sinus rhythm in 78 patients at 349 +/- 141
      days after thrombolysis for a first anterior myocardial infarction. Visual map
      analysis was directed at discriminating dipolar (uniform repolarization) from
      nondipolar (nonuniform repolarization) patterns. In addition, the nondipolar
      content of each map was assessed quantitatively with the use of eigenvector
      analysis. Nondipolar map patterns were present in almost one third of the
      patients (32%). Left ventricular end-systolic and end-diastolic volumes were
      assessed echocardiographically before discharge and after 3 and 12 months with
      the use of the modified biplane Simpson rule. The increase in left ventricular
      end-systolic volume 1 year after myocardial infarction was more pronounced in
      patients with nondipolar QRST integral map patterns (14.47 +/- 14.10 versus 4.22
      +/- 8.44 mL/m2, P = .017). In patients with an increase in end-systolic volume of
      more than 16 mL/m2 (upper quartile), the prevalence of nondipolar maps was 89%
      compared with 29% in patients with dilatation of less than 16 mL/m2. In addition,
      the nondipolar content of maps in patients in the upper quartile was
      significantly increased compared with the lower quartiles (49 +/- 14% versus 37
      +/- 12%, P = .013). Logistic regression analysis revealed that an end-systolic
      volume of more than 42 mL/m2 after 1 year contributed independently to the
      appearance of nondipolar maps. Patients with high-grade ventricular arrhythmias
      showed a higher nondipolar content (49 +/- 17% versus 39 +/- 10%, P = .013). QTc
      dispersion did not discriminate between patients with and those without high
      grade ventricular arrhythmias. Also, the association between left ventricular
      remodeling and nondipolar map patterns was confirmed prospectively in an
      additional group of 15 patients. CONCLUSIONS: Nondipolar map patterns are present
      in 32% of patients after thrombolysis for a first anterior myocardial infarction
      and are associated with increased left ventricular dilatation. These data support
      the hypothesis that left ventricular dilatation after myocardial infarction leads
      to changes in repolarization characteristics that may facilitate the occurrence
      of life-threatening ventricular arrhythmias.

PMID- 7634443
TI  - Length of hospital stay and complications after percutaneous transluminal
      coronary angioplasty. Clinical and procedural predictors. Heparin Registry
      Investigators.
AB  - BACKGROUND: Although several studies have established that the complications of
      percutaneous transluminal coronary angioplasty (PTCA) are related to clinical and
      angiographic variables such as advanced age and lesion complexity, it is
      uncertain whether the use of hospital resources after PTCA also depends on the
      same baseline variables. The purpose of this study was to identify the factors
      responsible for prolonged hospital stay after PTCA. METHODS AND RESULTS: The
      study cohort included 591 consecutive patients undergoing conventional balloon
      angioplasty at nine medical centers in North America. Major or minor
      complications occurred in 91 patients (15.4%) and were observed to be related to
      several baseline characteristics, including unstable angina, multivessel coronary
      artery disease, patient age, and lesion complexity. Compared with a median length
      of hospital stay of 2.0 days after PTCA (25th, 75th percentiles: 2.0, 4.0) for
      the entire cohort of patients, the length of stay was increased in patients with
      unstable angina (3.0 days [2.0, 5.0]; P = .002), multivessel coronary artery
      disease (3.0 [2.0, 5.5]; P = .001), age > 65 years (3.0 [2.0, 5.5]; P = .02),
      complex lesions (3.0 [2.0, 6.0]; P = .001), and filling defects (6.0 [2.0, 11.0];
      P < .001). The length of stay was more strikingly increased, however, in patients
      who experienced major or minor PTCA complications, such as emergency bypass
      surgery (9.0 days [8.0, 18.0]; P < .001), Q-wave or non-Q-wave myocardial
      infarction (8.0 [6.0, 15.5]; P < .001), transfusion unrelated to bypass surgery
      (8.0 [4.0, 12.0]; P < .001), or abrupt vessel closure (6.0 [3.0, 10.5]; P <
      .001). On stepwise multiple linear regression, PTCA complications appeared to be
      the strongest predictors of length of hospital stay (all P < .001) and
      overwhelmed the weaker relation between length of stay and several individual
      baseline variables. Inclusion of a composite clinical risk score (reflecting the
      presence of unstable angina, multivessel disease, advanced age, complex lesions,
      or filling defects) in the regression model confirmed that patients with several
      high-risk baseline variables had a significant increase in length of stay after
      PTCA (P = .003), but PTCA complications remained the strongest predictors of
      length of stay. CONCLUSIONS: Although PTCA complications were correlated with
      baseline variables such as unstable angina, multivessel disease, advanced age,
      complex lesions, and filling defects, excess length of stay after PTCA was most
      strongly influenced by the development of minor and major PTCA complications.
      Because patients with several baseline risk factors experienced significantly
      prolonged hospitalizations, improved selection of patients may contribute to
      reductions in length of stay after PTCA. A greater reduction in resource use
      after PTCA, however, would be expected from developing new treatments to decrease
      PTCA complications rather than limiting the access of patients with unstable
      angina, advanced age, or complex lesions to PTCA.

PMID- 7634444
TI  - Contribution of nitric oxide to metabolic coronary vasodilation in the human
      heart.
AB  - BACKGROUND: The vascular endothelium contributes to smooth muscle relaxation by
      tonic release of nitric oxide. To investigate the contribution of nitric oxide to
      human coronary epicardial and microvascular dilation during conditions of
      increasing myocardial oxygen requirements, we studied the effect of inhibiting
      nitric oxide synthesis with NG-monomethyl-L-arginine (L-NMMA) on the coronary
      vasodilation during cardiac pacing in patients with angiographically normal
      coronary arteries with and without multiple risk factors for coronary
      atherosclerosis. METHODS AND RESULTS: In 26 patients with angiographically normal
      or near-normal epicardial coronary arteries, metabolic vasodilation was assessed
      as a change in coronary vascular resistance and diameter during cardiac pacing
      (mean heart rate, 141 beats per minute). Endothelium-dependent vasodilation was
      estimated with intracoronary acetylcholine and endothelium-independent dilation
      with intracoronary sodium nitroprusside and adenosine. These measurements were
      repeated after 64 mumol/min intracoronary L-NMMA. At rest, L-NMMA produced a 16
      +/- 25% (mean +/- SD) increase in coronary vascular resistance (P < .05) and an
      11% reduction in distal epicardial coronary artery diameter (P < .01), indicating
      tonic basal release of nitric oxide from human coronary epicardial vessels and
      microvessels. Significant inhibition of pacing-induced metabolic coronary
      vascular dilation occurred with L-NMMA, coronary vascular resistance was 38 +/-
      56% higher (P < .03), and epicardial coronary dilation during control pacing (9
      +/- 13%) was converted to constriction after L-NMMA and pacing (-6 +/- 9%, P <
      .04). L-NMMA specifically inhibited endothelium-dependent vasodilation with
      acetylcholine (coronary vascular resistance was 72% higher [P < .01]) but did not
      alter endothelium-independent dilation with sodium nitroprusside and adenosine.
      Nine patients had no major risk factors for atherosclerosis, defined as serum
      cholesterol > 240 mg/dL, hypertension, or diabetes. The remaining 17 patients
      with one or more of these risk factors had depressed microvascular vasodilation
      during cardiac pacing (coronary vascular resistance decreased by 13% versus 36%
      in those without risk factors, P < .05). The inhibitory effect of L-NMMA on
      pacing-induced coronary epicardial and microvascular vasodilation was observed
      only in patients without risk factors, whereas those with risk factors had an
      insignificant change, indicating that nitric oxide contributes significantly to
      pacing-induced coronary vasodilation in patients free of risk factors and without
      endothelial dysfunction. Patients with risk factors also had reduced vasodilation
      with acetylcholine (40 +/- 28% versus 68 +/- 8% decrease in coronary vascular
      resistance, P < .01), but the responses to sodium nitroprusside were similar in
      both groups. CONCLUSIONS: During metabolic stimulation of the human heart, nitric
      oxide release contributes significantly to microvascular vasodilation and is
      almost entirely responsible for the epicardial vasodilation. This contribution of
      nitric oxide is reduced in patients exposed to risk factors for coronary
      atherosclerosis and leads to a net reduction in vasodilation during stress. An
      important implication of these findings is that reduced nitric oxide
      bioavailability during stress in patients with atherosclerosis or risk factors
      for atherosclerosis may contribute to myocardial ischemia by limiting epicardial
      and microvascular coronary vasodilation.

PMID- 7634446
TI  - Infarct size after acute myocardial infarction measured by quantitative
      tomographic 99mTc sestamibi imaging predicts subsequent mortality.
AB  - BACKGROUND: 99mTc sestamibi is a recently developed radioisotope that has been
      used to measure myocardium at risk and infarct size. The relation between these
      measurements and subsequent patient outcome has not yet been demonstrated.
      METHODS AND RESULTS: Two hundred seventy-four consecutive patients with acute
      myocardial infarction underwent tomographic 99mTc sestamibi imaging on arrival at
      the hospital (to measure myocardium at risk before reperfusion therapy) and at
      hospital discharge (to measure the amount of salvaged myocardium and final
      infarct size). Defect size on the sestamibi images was quantified using a
      threshold value of 60% of peak counts from the circumferential count profile
      curves generated for five representative slices of the left ventricle. Patients
      were followed after hospital discharge to evaluate the association between final
      infarct size and subsequent mortality. The median defect size measured was 27% of
      the left ventricle at presentation to the hospital (range, 0% to 77%) and was 12%
      of the left ventricle at hospital discharge (range, 0% to 68%). Almost one half
      of the patients had a final infarct size of < or = 10%. The median amount of
      myocardium salvaged was 9% (range, -31% to 75%). During a median duration of
      follow-up of 12 months, there were 10 deaths (7 cardiac and 3 noncardiac) and 1
      resuscitated out-of-hospital cardiac arrest. There was a significant association
      between infarct size and overall mortality (chi 2 = 8.66, P = .003) and cardiac
      mortality (chi 2 = 11.89, P < .001). Two-year mortality was 7% for patients whose
      infarct size was > or = 12% versus 0% for patients whose infarct size was < 12%.
      There also was a significant association between myocardium at risk and cardiac
      mortality (chi 2 = 6.87, P = .009). There was no association between myocardium
      at risk and overall mortality or between amount of myocardium salvaged and either
      overall mortality or cardiac mortality. CONCLUSIONS: Larger infarct size measured
      by 99mTc sestamibi imaging after acute myocardial infarction is associated with
      increased mortality risk during short-term follow-up.

PMID- 7634445
TI  - Job strain and the prevalence and outcome of coronary artery disease.
AB  - BACKGROUND: It has been hypothesized that jobs that have both high psychological
      demands and low decision latitude ("job strain") can lead to coronary disease.
      The objective of this study was to test whether job strain was correlated with
      the presence of coronary disease at angiography or with long-term outcome in
      patients with angiographic coronary disease. METHODS AND RESULTS: Employed
      patients under the age of 65 years undergoing diagnostic coronary angiography
      completed a self-administered questionnaire about their job duties and work
      environment. Job strain was measured by the method of Karasek. Patients were
      separated into three groups, based on extent of coronary disease: significant
      disease (> or = 75% stenosis), insignificant disease (> 0% but < 75% stenosis),
      and normal coronary arteries. Statistical analyses were performed using logistic
      regression and the Cox proportional hazards model. The 1489 patients enrolled had
      a median age of 52 years; 76% were male and 88% were white. By design, all
      patients were employed, 60% in white-collar jobs and only 16% in jobs requiring
      heavy labor. Traditional cardiac risk factors were most prevalent in the 922
      patients with significant coronary artery disease, at intermediate levels in the
      204 patients with insignificant disease, and least prevalent in the 363 patients
      with normal coronary arteries (all P < .01). Job strain was actually more common
      in patients with normal coronary arteries (35%) than in patients with
      insignificant (26%) or significant disease (25%, P < .002). In a multivariate
      analysis, job strain was not significantly correlated with the presence of
      coronary disease. Job strain was not correlated with angina frequency at the time
      of angiography. Job strain was not a predictor of cardiac events (cardiac death
      or nonfatal myocardial infarction) during follow-up. CONCLUSIONS: Job strain was
      not correlated with the prevalence or severity of coronary artery disease in a
      cohort of patients undergoing coronary angiography. The outcome of patients with
      angiographically defined coronary disease was not affected by the level of job
      strain as measured by the method of Karasek.

PMID- 7634447
TI  - Relation between diastolic perfusion time and coronary artery stenosis during
      stress-induced myocardial ischemia.
AB  - BACKGROUND: Experimental studies have demonstrated that during stress-induced
      myocardial ischemia, coronary obstruction and diastolic perfusion time are
      factors that limit subendocardial perfusion and correlate to degree of myocardial
      dysfunction. The relation between these two factors has not yet been investigated
      in humans. The aim of the present study was to assess the relation between
      diastolic perfusion time and degree of coronary stenosis during different types
      of stress tests. METHODS AND RESULTS: Nine patients with isolated and proximal
      stenosis of the left anterior descending coronary artery were selected. Patients
      underwent three different randomized stress tests (upright, supine bicycle stress
      test, and transesophageal atrial pacing). Diastolic perfusion time, heart rate
      (RR interval), and systolic and diastolic pressures were measured during the test
      and at the ischemic threshold (0.1-mV ST-segment depression). Angiographic
      measurements of coronary stenosis were evaluated by quantitative coronary
      angiography. At the ischemic threshold, significant differences among tests were
      found in heart rate (P < .05), systolic pressure (P < .001), and diastolic
      pressure (P < .05). In each stress test, diastolic perfusion time at the ischemic
      threshold was closely correlated with minimal stenosis diameter (r = .97; P <
      .001) and percent diameter stenosis (r = .92; P < .001) with no difference among
      the tests. In contrast, heart rate, rate-pressure product, and time to ischemic
      threshold were not significantly correlated with percent diameter stenosis and
      minimal stenosis diameter. No significant correlation was observed at the
      ischemic threshold between diastolic perfusion time and corresponding values of
      heart rate, despite the close correlation at rest (r = .95; P < .001).
      CONCLUSIONS: Despite differences in associated hemodynamic responses to various
      stress tests, a close relation exists between stenosis severity and diastolic
      perfusion time at the onset of stress-induced myocardial ischemia. Therefore,
      diastolic perfusion time at the ischemic threshold may be an indirect estimate of
      the hemodynamic significance of coronary stenosis.

PMID- 7634448
TI  - Early and late quantitative angiographic results of vein graft lesions treated by
      excimer laser with adjunctive balloon angioplasty.
AB  - BACKGROUND: Percutaneous excimer laser coronary angioplasty (PELCA) has been
      approved for treatment of diseased saphenous vein bypass grafts. However,
      detailed and complete quantitative angiographic analysis of immediate procedural
      and late follow-up results has not been performed. METHODS AND RESULTS: PELCA
      using the CVX-300 excimer laser system was performed in 125 bypass lesions (mean
      graft age, 96 +/- 53 months; range, 2 to 240 months) in 106 consecutive patients
      at eight centers. Quantitative analyses of the procedural and follow-up
      angiograms were done with the Cardiac Measurement System. Stand-alone PELCA was
      done in 21 lesions (17%). Lesions were located at the ostium (20%), body (67%),
      or distal anastomosis (13%). The graft reference diameter was 3.26 +/- 0.79 mm
      (mean +/- SD). Minimal lumen diameter increased from 1.09 +/- 0.52 mm before
      treatment to 1.61 +/- 0.69 mm after laser and 2.18 +/- 0.63 mm after adjunctive
      balloon dilation (P < .001) but had declined at follow-up to 1.40 +/- 1.17 mm.
      Dissections were evident in 45% of lesions after laser treatment (types A and B,
      27%; types C through F, 18%), including 7% occlusions. Angiographic success (< or
      = 50% diameter stenosis [% DS]) was 54% after laser and 91% after adjunctive
      PTCA, with an overall clinical success rate of 89%. In-hospital complications
      were death, 0.9%; myocardial infarction (Q-wave and non-Q-wave), 4.5%; and bypass
      surgery, 0.9%. Independent predictors of % DS after laser were reference
      diameter, lesion length, and minimal lumen diameter before laser. At angiographic
      follow-up in 83% of eligible patients, the restenosis rate per lesion (DS > 50%)
      was 52%, including 23 occlusions (24%). The only independent predictor of
      increased % DS at follow-up was lesion symmetry. Logistic regression indicated
      that smaller reference diameter was an independent predictor of late occlusion.
      Overall 1-year mortality was 8.6%. Actuarial event-free survival (freedom from
      death, myocardial infarction, bypass surgery, or target vessel percutaneous
      transluminal coronary angioplasty) was 48.2% at 1 year. CONCLUSIONS: Excimer
      laser angioplasty with adjunctive balloon angioplasty can be safely and
      successfully performed in diseased, old saphenous vein bypass graft lesions
      considered at high risk for reintervention. The extent of laser ablation remains
      limited by the diameter and effectiveness of the catheters. Late restenosis and,
      in particular, total occlusion mitigate the early benefits of the procedure.
      Other approaches such as the routine use of additional anticoagulation (eg,
      warfarin) should be considered to reduce the risk of late occlusions and
      restenosis after laser angioplasty of bypass grafts.

PMID- 7634449
TI  - Endothelin ETA and ETB receptors cause vasoconstriction of human resistance and
      capacitance vessels in vivo.
AB  - BACKGROUND: The role of endothelin ETB receptors in mediating vasoconstriction in
      humans is unclear. As yet, there have been no in vivo studies in resistance
      vessels, and in vitro data have been contradictory. We therefore investigated the
      function of ETB receptors in vivo in human forearm resistance and hand
      capacitance vessels using endothelin-1 as a nonselective agonist at ETA and ETB
      receptors and endothelin-3 and sarafotoxin S6c as selective agonists at the ETB
      receptor. METHODS AND RESULTS: A series of single-blind studies were performed,
      each in six healthy men. Brachial artery infusion of endothelin-1 and endothelin
      3 caused slow-onset dose-dependent forearm vasoconstriction. Although endothelin
      3 caused significantly less forearm vasoconstriction than endothelin-1 at low
      doses, vasoconstriction was similar to the two isopeptides at the highest dose
      (60 pmol/min). Endothelin-3 caused transient forearm vasodilatation at this dose,
      whereas endothelin-1 showed only a nonsignificant trend toward causing early
      vasodilatation. Intra-arterial sarafotoxin S6c caused a progressive reduction in
      forearm blood flow, although less than that to endothelin-1 (P = .04). Dorsal
      hand vein infusion of sarafotoxin S6c caused local venoconstriction that was also
      less than that to endothelin-1 (P = .002). CONCLUSIONS: Selective ETB receptor
      agonists cause constriction of forearm resistance and hand capacitance vessels in
      vivo in humans, suggesting that both ETA and ETB receptors mediate
      vasoconstriction. Hence, antagonists at both ETA and ETB receptors, or inhibitors
      of the generation of endothelin-1, may be necessary to completely prevent
      vasoconstriction to endogenously generated endothelin-1.

PMID- 7634450
TI  - HDLs containing apolipoproteins A-I and A-II (LpA-I:A-II) as markers of coronary
      artery disease in men with non-insulin-dependent diabetes mellitus.
AB  - BACKGROUND: Abnormalities in HDL and an increased risk of coronary artery disease
      (CAD) coexist in non-insulin-dependent diabetes mellitus (NIDDM). HDLs can be
      separated by their apolipoprotein (apo) content into particles containing apoA-I
      but not apoA-II (LpA-I) and those containing both apoA-I and apoA-II (LpA-I:A
      II). The LpA-I particles have been suggested to be more effective in conferring
      protection against CAD than the LpA-I:A-II particles. However, data are sparse,
      and no studies have defined the role of these two classes of particles in NIDDM.
      METHODS AND RESULTS: LpA-I and LpA-I:A-II particles were quantified by a
      differential electroimmunoassay in four groups of men with similar age and body
      mass index (BMI) distributions. Group 1 consisted of 50 patients with NIDDM and
      angiographically verified CAD; group 2, 50 men with CAD but no diabetes; group 3,
      50 men with NIDDM but no CAD; and group 4, 31 healthy men. Serum apoA-I and apoA
      II concentrations were measured by immunoturbidimetry, and HDL2 and HDL3 were
      separated by ultracentrifugation. Concentrations of LpA-I:A-II particles in group
      1 were 13.8%, 18.3%, and 26.9% lower than in groups 2 through 4, respectively. In
      a two-by-two factorial ANOVA, adjusted for age and BMI, the differences were
      significant for both CAD (P < .001) and NIDDM (P < .001), with no interaction
      between the factors. These results were confirmed by comparable differences in
      the serum concentrations of apoA-I and apoA-II. LpA-I particles were related to
      the presence or absence of CAD (P = .013), but the difference was lost in a
      multivariate analysis. A low HDL3 cholesterol concentration characterized both
      CAD (P = .002) and NIDDM (P = .024). HDL2 cholesterol differed significantly with
      regard to the presence of NIDDM (P = .033) but only borderline with respect to
      CAD (P = .073). CONCLUSIONS: ApoA-II-containing lipoproteins and HDL3 cholesterol
      are powerful markers of CAD in men with NIDDM.

PMID- 7634451
TI  - Mechanism of adenosine-induced elevation of pulmonary capillary wedge pressure in
      humans.
AB  - BACKGROUND: Continuous intravenous administration of adenosine to humans often
      results in a paradoxical rise in pulmonary capillary wedge pressure (PCWP),
      whereas arterial resistance is lowered and cardiac output and heart rate
      increase. This is believed to be due to diastolic stiffening of the ventricle or
      to a negative inotropic effect. In the present study, we tested these and other
      mechanisms by using pressure-volume (PV) analysis and echocardiography. METHODS
      AND RESULTS: Fifteen patients with normal rest left ventricular function
      underwent cardiac catheterization and received adenosine at a rate of 140
      micrograms/kg per minute IV for 6 to 10 minutes. PV relations were measured in 9
      patients (without coronary artery disease) using the conductance catheter method.
      In 6 additional patients with coronary artery disease, echocardiograms were used
      to assess wall thickness and function, and aortic and coronary sinus blood,
      lactate, oxygen, and adenosine levels were measured. Adenosine increased PCWP by
      19% (+2.6 mm Hg) in both patient groups while lowering arterial load by 30% and
      increasing cardiac output by 45% (all P < .001). There was no significant effect
      of adenosine on mean linear chamber compliance or monoexponential elastic
      stiffness, as the diastolic PV relation was unchanged in most patients. Diastolic
      wall thickness also was unaltered. Thus, the PCWP rise did not appear to be due
      to diastolic stiffening. Adenosine induced a rightward shift of the end-systolic
      PV relation (ESPVR) (+12.7 +/- 3.7 mL) without a slope change. This shift likely
      reflected effects of afterload reduction, as other indexes (stroke work-end
      diastolic volume relation and dP/dtmax at matched preload) were either unchanged
      or increased. Furthermore, this modest shift in ESPVR was more than compensated
      for by vasodilation and tachycardia, so reduced systolic function could not
      explain the increase in PCWP. There also was no net lactate production to suggest
      ischemia. Rather than arising from direct myocardial effects, PCWP elevation was
      most easily explained by a change in vascular loading, as both left ventricular
      end-diastolic volume and right atrial pressure increased (P < .05). This suggests
      that adenosine induced a redistribution of blood volume toward the central
      thorax. CONCLUSIONS: PCWP elevation in response to adenosine primarily results
      from changes in vascular loading rather than from direct effects on cardiac
      diastolic or systolic function.

PMID- 7634452
TI  - Relationship of cardiovascular risk factors to echocardiographic left ventricular
      mass in healthy young black and white adult men and women. The CARDIA study.
      Coronary Artery Risk Development in Young Adults.
AB  - BACKGROUND: The objective of this study was to describe the distribution of echo
      left ventricular (LV) mass and its association with demographic and
      cardiovascular risk factors in a large race- and sex-balanced cohort of young
      adults. Recent epidemiological data have suggested that M-mode
      echocardiographically determined LV hypertrophy is an independent predictor of
      mortality and morbidity from coronary heart disease (CHD) in older adults.
      Echocardiographic LV mass has been associated in middle-aged and older adults
      with multiple factors including age, arterial blood pressure, body mass, and sex.
      However, there are few data describing the distribution of echo LV mass among
      black and white young adult men and women and relating LV mass to cardiovascular
      disease risk factors within race-sex subgroups. METHODS AND RESULTS: CARDIA
      (Coronary Artery Risk Development in Young Adults) is a multicenter study of
      young adults, including approximately equal proportions of black and white men
      and women aged 23 to 35 years at the time of echo examination (1990 through
      1991). Two-dimensionally guided M-mode echocardiograms were attempted in 4243
      participants with recordings deemed acceptable for calculation of LV mass, that
      is, of at least fair quality score, obtained in 3840 (90.5% of the 1990-1991
      cohort). M-mode LV mass was calculated from the formula of Devereux and Reicheck,
      adapted for use with measurements made according to the American Society of
      Echocardiography Standards. LV mass was greater in men than in women and greater
      in blacks than in whites (P < .001) (mean +/- SD): black men, 176 +/- 42 g; white
      men, 169 +/- 40 g; black women, 135 +/- 38 g; and white women, 125 +/- 33 g. In
      all race-sex groups, LV mass was positively correlated (P < .0001) in bivariate
      analyses with body weight, subcapular skinfold thickness, height, and systolic
      blood pressure. In multivariate analyses, LV mass remained independently and
      positively related to body weight and systolic blood pressure and, when body
      weight was not considered, with subcapular skinfold thickness and height. In
      addition, the multivariate models allowed us to infer a direct relation between
      LV mass and both fatness and lean body mass. Weaker positive associations were
      noted of LV mass with pulse pressure in white participants and with physical
      activity in men. After adjustment for subscapular skinfold thickness, height,
      systolic and diastolic blood pressures, alcohol consumption, pulmonary function,
      smoking history, physical activity, total serum cholesterol, and family history
      of hypertension, LV mass remained higher in men than in women (P < .0001), in
      black men (167 +/- 43 g) than in white men (156 +/- 50 g, P < .0001), and in
      black women (142 +/- 49 g) than in white women (137 +/- 43 g, P < .002).
      CONCLUSIONS: In the healthy young adults of the CARDIA cohort, LV mass was highly
      correlated with body weight, subscapular skinfold thickness, height, and systolic
      blood pressure across race and sex subgroups. Furthermore, after adjustment for
      anthropometric, blood pressure, and other covariates, LV mass remained higher in
      men than in women and in blacks than in whites. Longitudinal studies are
      necessary to delineate the possible roles of these factors in the genesis of LV
      hypertrophy.

PMID- 7634453
TI  - Relationship of the third heart sound to transmitral flow velocity deceleration.
AB  - BACKGROUND: The third heart sound (S3) occurs shortly after the early (E-wave)
      peak of the transmitral diastolic Doppler velocity profile (DVP). It is thought
      to be due to cardiohemic vibrations powered by rapid deceleration of transmitral
      blood flow. Although the presence, timing, and clinical correlates of the S3 have
      been extensively characterized, derivation and validation of a causal,
      mathematical relation between transmitral flow velocity and the S3 are lacking.
      METHODS AND RESULTS: To characterize the kinematics and physiological mechanisms
      of S3 production, we modeled the cardiohemic system as a forced, damped,
      nonlinear harmonic oscillator. The forcing term used a closed-form mathematical
      expression for the deceleration portion of the DVP. We tested the hypothesis that
      our model's predictions for amplitude, timing, and frequency of S3 accurately
      predict the transthoracic phonocardiogram, using the simultaneously recorded
      transmitral Doppler E wave as input, in three subject groups: those with audible
      pathological S3, those with audible physiological S3, and those with inaudible
      S3. CONCLUSIONS: We found excellent agreement between model prediction and the
      observed data for all three subject groups. We conclude that, in the presence of
      a normal mitral valve, the kinematics of filling requires that all hearts have
      oscillations of the cardiohemic system during E-wave deceleration. However, the
      oscillations may not have high enough amplitude or frequency to be heard as an S3
      unless there is sufficiently rapid fluid deceleration (of the Doppler E-wave
      contour) with sufficient cardiohemic coupling.

PMID- 7634454
TI  - Evidence for preserved cardiopulmonary baroreflex control of renal cortical blood
      flow in humans with advanced heart failure. A positron emission tomography study.
AB  - BACKGROUND: The effect of cardiopulmonary baroreflexes on the renal circulation
      in healthy humans and patients with heart failure is unknown because of the
      technical limitations of studying the renal circulation. Positron emission
      tomography (PET) imaging is a new method to measure renal cortical blood flow in
      humans that is precise, rapid, reproducible, and noninvasive. The purpose of this
      study was to compare the effect of acute cardiopulmonary baroreceptor unloading
      by phlebotomy on regional blood flow in healthy humans and humans with advanced
      heart failure. METHODS AND RESULTS: We compared renal cortical blood flow and
      forearm blood flow in 10 healthy volunteers and 8 patients with heart failure
      (left ventricular ejection fraction, 0.24 +/- 0.02) during cardiopulmonary
      baroreceptor unloading with phlebotomy (450 mL). The major findings of this study
      are: (1) At rest, renal cortical blood flow is markedly diminished in humans with
      heart failure compared with healthy humans (heart failure, 2.4 +/- 0.1 versus
      healthy, 4.3 +/- 0.2 mL.min-1.g-1, P < .001). (2) In healthy humans, during
      phlebotomy, forearm blood flow decreased substantially (basal, 3.3 +/- 0.4 versus
      phlebotomy, 2.6 +/- 0.3 mL.min-1.100 mL-1, P = .02) and renal cortical blood flow
      decreased slightly but significantly (basal, 4.3 +/- 0.2 versus phlebotomy, 4.0
      +/- 0.3 mL.min-1.g-1, P = .01). (3) The small magnitude of reflex renal
      vasoconstriction is not explained by the inability of the renal circulation to
      vasoconstrict, since the cold pressor stimulus induced substantial decreases in
      renal cortical blood flow in healthy subjects (basal, 4.4 +/- 0.1 versus cold
      pressor, 3.7 +/- 0.1 mL.min-1.g-1, P = .003). (4) In humans with heart failure,
      during phlebotomy, forearm blood flow did not change (basal, 2.6 +/- 0.3 versus
      phlebotomy, 2.7 +/- 0.2 mL.min-1.100 mL-1, P = NS), but renal cortical blood flow
      decreased slightly but significantly (basal, 2.4 +/- 0.1 versus phlebotomy, 2.1
      +/- 0.1 mL.min-1.g-1, P = .01). (5) The cold pressor stimulus induced substantial
      decreases in renal cortical blood flow in patients with heart failure (basal, 2.9
      +/- 0.1 versus cold pressor, 2.3 +/- 0.1 mL.min-1.g-1, P = .008). Thus, in
      patients with heart failure, there is an abnormality in cardiopulmonary
      baroreflex control of the forearm circulation but not the renal circulation.
      CONCLUSIONS: This study demonstrates the power of PET imaging to study normal
      physiological and pathophysiological reflex control of the renal circulation in
      humans and describes the novel finding of selective dysfunction of
      cardiopulmonary baroreflex control of one vascular region but its preservation in
      another in patients with heart failure.

PMID- 7634455
TI  - Evidence against reinnervation of cardiac vagal afferents after human orthotopic
      cardiac transplantation.
AB  - BACKGROUND: Orthotopic cardiac transplantation results in total cardiac
      denervation. Recent studies in humans suggest that reinnervation of cardiac
      sympathetic nerves (cardiac efferents) may occur after cardiac transplantation.
      We hypothesized that reinnervation of cardiac afferents may occur as well. To
      test this hypothesis, we investigated reflex responses produced by stimulation of
      ventricular chemosensory endings subserved by vagal afferents (cardiac depressor
      reflex). METHODS AND RESULTS: Two cardiac transplant groups were studied: an
      "early" group (n = 18, < 24 months after transplant) and a "late" group (n = 18,
      > 43 months after transplant); these groups were compared with a control group
      with intact innervation (n = 18). The reflex response of the recipient sinus node
      (RSN) in the remnant right atrium, which remains innervated after
      transplantation, was observed during selective right coronary artery (RCA) and
      left coronary artery (LCA) injection of the radiographic contrast agent meglumine
      diatrizoate, which is known to stimulate ventricular chemosensory endings. A
      decrease in the rate of the RSN was expected if reinnervation of chemosensory
      endings had occurred and the afferent limb of the cardiac depressor reflex was
      intact. With injection, the RSN rate of both transplant groups did not decrease
      but increased (early: LCA, 7.2 +/- 1.4 beats per minute; RCA, 6.3 +/- 1.3 beats
      per minute; late: LCA, 5.9 +/- 1.0 beats per minute; RCA, 6.0 +/- 0.9 beats per
      minute) compared with the expected decrease in control patients (LCA, -20.8 +/-
      2.5 beats per minute; RCA, -18.0 +/- 4.0 beats per minute; P < .001 versus
      transplants). Decreases in mean arterial pressure in the transplant groups
      (early: LCA, -11.3 +/- 1.4 mm Hg; RCA, -10.0 +/- 1.6 mm Hg; late: LCA, -13.0 +/-
      1.6 mm Hg; RCA, -9.1 +/- 1.5 mm Hg) were less than those observed in the control
      group (LCA, -19.8 +/- 2.2 mm Hg; RCA, -18.7 +/- 4.0 mm Hg; P < .05 versus
      transplants). CONCLUSIONS: The results suggest that reinnervation of ventricular
      chemosensory endings subserved by vagal afferents in cardiac transplant patients
      does not occur up to 74 months after transplantation.

PMID- 7634456
TI  - Circulating cardiac troponin T in potential heart transplant donors.
AB  - BACKGROUND: Brain death may induce myocardial dysfunction, the mechanisms of
      which are not yet fully understood. Circulating cardiac troponin T is considered
      a highly sensitive and specific marker of myocardial cell injury. METHODS AND
      RESULTS: We prospectively measured circulating cardiac troponin T in 100 brain
      dead patients and measured the left ventricular ejection fraction area (LVEFa),
      using transesophageal echocardiography. Sixty-one patients had normal LVEFa, 25
      had moderate decrease in LVEFa (30% to 50%), and 14 had severe decrease in LVEFa
      (< or = 30%). Circulating cardiac troponin T concentrations were significantly
      higher (1.68 +/- 1.03 micrograms/L-1, P < .01) in patients with a severe decrease
      in LVEFa than in the two other groups (0.42 +/- 0.43 and 0.12 +/- 0.16
      microgram/L-1, respectively), and there was a significant correlation between
      LVEFa and cardiac troponin T concentration (p = -0.59, P < .0001). An elevated
      circulating cardiac troponin T concentration (> or = 0.5 microgram/L-1) was more
      accurate (sensitivity, 1.00; specificity, 0.84) in predicting a severe decrease
      in LVEFa than an elevated CKMB value or an increased CKMB/CK ratio. CONCLUSIONS:
      An elevated circulating cardiac troponin T was associated with a severe decrease
      in LVEFa in brain-dead patients, suggesting that severe and potentially
      irreversible myocardial cell damage occurred. In contrast, CKMB determination was
      not useful. Since the quality of the donor's heart is considered an important
      prognosis factor in heart transplantation, the determination of circulating
      cardiac troponin T concentration could be useful to the heart transplantation
      team.

PMID- 7634457
TI  - Human heart-infiltrating T-cell clones from rheumatic heart disease patients
      recognize both streptococcal and cardiac proteins.
AB  - BACKGROUND: beta-Hemolytic streptococcal infection in developing countries still
      causes thousands of causes of rheumatic heart disease, demanding surgical valve
      correction. Antigenic mimicry between self and streptococcal components has been
      proposed as the triggering factor leading to autoimmunity in individuals with
      genetic susceptibility. Although heart streptococcal-M protein cross-reactive
      antibodies have been demonstrated, heart tissue damage seems to be T lymphocyte
      dependent. We studied the infiltrating T lymphocytes in rheumatic heart lesions
      with the aim of understanding the role of cellular immune response at the site of
      the lesions. METHODS AND RESULTS: We obtained 107 T-cell clones from surgical
      fragments of cardiac tissue from four rheumatic heart disease patients. We tested
      their capacity to recognize streptococcal M protein-derived synthetic peptides
      and heart proteins. We found eight infiltrating T-cell clones from all four
      patients that simultaneously recognize streptococcal M and heart proteins. Among
      the M-protein sequences tested, only synthetic peptides corresponding to regions
      1 through 25, 81 through 103, and 163 through 177 were simultaneously recognized
      with heart protein fractions. Interestingly, regions 81 through 103 and 163
      through 177 have been known to bear heart cross-reactive epitopes at the antibody
      level. Five of these clones are CD4+, and one is CD8+. CONCLUSIONS: The presence
      of heart-M protein cross-reactive T-cell clones in rheumatic heart lesions
      suggests their direct involvement in the pathogenesis of this disease. The
      dissection of protective and pathogenic epitopes of streptococcal M protein is an
      important step in allowing the development of a safe anti-streptococcal synthetic
      vaccine.

PMID- 7634459
TI  - The risk of atrial fibrillation following radiofrequency catheter ablation of
      atrial flutter.
AB  - BACKGROUND: Although radiofrequency catheter ablation of atrial flutter is
      associated with a high rate of initial success, several clinical issues regarding
      this therapy remain to be defined. For example, the risks of recurrent atrial
      flutter and of developing atrial fibrillation after flutter ablation are unknown.
      In addition, it is not known whether elimination of atrial flutter will modify
      the natural history of atrial fibrillation in patients who experience both of
      these arrhythmias. The purpose of the present study was to determine the
      actuarial freedom from recurrent or new atrial arrhythmias in patients with
      atrial flutter undergoing catheter ablation. METHODS AND RESULTS: The study
      population consisted of 59 consecutive patients (mean age, 61.9 +/- 12.6 years)
      with typical atrial flutter who underwent catheter ablation of the reentrant
      circuit. Catheter ablation was not advised for patients in whom paroxysmal atrial
      fibrillation had been a major clinical problem. The inducibility of atrial
      fibrillation and atrial flutter was assessed after successful atrial flutter
      ablation with programmed atrial stimulation and rapid atrial pacing to a cycle
      length of 180 ms or 2:1 atrial capture. Atrial flutter was successfully ablated
      and rendered noninducible in 53 of 59 patients (90%). Over a mean follow-up
      period of 13.2 +/- 6.6 months, atrial flutter recurred in 5 patients (9.4%).
      Atrial fibrillation occurred in 14 of 53 patients after successful ablation
      (26.4%). Four clinical variables were associated by univariate analysis with the
      late occurrence of atrial fibrillation: (1) the presence of structural heart
      disease, (2) a history of atrial fibrillation before ablation of atrial flutter,
      (3) inducible sustained atrial fibrillation after ablation, and (4) a greater
      number of failed antiarrhythmic drugs. By multivariate analysis, only the
      persistent inducibility of sustained atrial fibrillation predicted the later
      development of atrial fibrillation. CONCLUSIONS: Although atrial flutter ablation
      is highly effective and associated with a low risk of recurrent atrial flutter,
      atrial fibrillation continues to be a long-term risk for individuals undergoing
      this procedure. The risk of later atrial fibrillation is especially high for
      patients in whom sustained atrial fibrillation remains inducible after ablation
      of atrial flutter.

PMID- 7634458
TI  - Mechanism of repetitive monomorphic ventricular tachycardia.
AB  - BACKGROUND: The most common form of idiopathic ventricular tachycardia (VT) is
      repetitive monomorphic VT (RMVT), which is characterized by frequent ventricular
      ectopy and salvos of nonsustained VT with intervening sinus rhythm. Unlike most
      other forms of idiopathic VT, this tachycardia typically occurs at rest and is
      nonsustained. The mechanism of RMVT is undefined. Because of a common site of
      origin, the right ventricular outflow tract (RVOT), we hypothesized that RMVT is
      mechanistically related to paroxysmal sustained, exercise-induced VT, which has
      been shown to be consistent with cAMP-mediated triggered activity. Therefore, in
      this study, we sought to identify (1) the mechanism of RMVT at the cellular level
      by using electropharmacological probes known to activate either stimulatory or
      inhibitory G proteins and thereby modify intracellular cAMP levels, (2) potential
      autonomic triggers of RMVT through analysis of heart rate variability, and (3)
      whether well-characterized somatic activating mutations in the stimulatory G
      protein, G alpha s, underlie RMVT. METHODS AND RESULTS: Twelve patients with RMVT
      underwent electrophysiological study. Sustained monomorphic VT was reproducibly
      initiated and terminated with programmed stimulation and/or isoproterenol
      infusion in 11 of the 12 patients (the other patient had incessant RMVT).
      Induction of VT demonstrated cycle length dependence and was facilitated by rapid
      atrial or ventricular pacing. Termination of VT occurred in response to
      interventions that either lowered stimulated levels of intracellular cAMP (and
      thus decreased intracellular Ca2+)--ie, adenosine (12 of 12), vagal maneuvers or
      edrophonium (8 of 9), and beta-blockade (3 of 5)--or directly decreased the slow
      inward calcium current--ie, verapamil (10 of 12). Analysis of heart rate
      variability during 24-hour ambulatory monitoring in 7 patients showed that the
      sinus heart rate is increased and accelerates before nonsustained VT (P < .05),
      whereas high-frequency heart rate variability is unchanged. These findings are
      consistent with transient increases in sympathetic tone preceding nonsustained
      VT. Finally, myocardial biopsy samples were obtained from the site of origin of
      the VT (typically the RVOT) and from the right ventricular apex from 9 patients.
      Genomic DNA was extracted from each biopsy sample, and three exons of G alpha s
      in which activating mutations have previously been described were amplified by
      polymerase chain reaction. All sequences from these regions were found to be
      identical to that of control. CONCLUSIONS: Although the arrhythmia occurs at
      rest, the constellation of findings in idiopathic VT that is characterized by
      RMVT is consistent with the mechanism of cAMP-mediated triggered activity.
      Therefore, the spectrum of VT resulting from this mechanism includes not only
      paroxysmal exercise-induced VT but also RMVT.

PMID- 7634460
TI  - Coronary sinus morphology in patients with atrioventricular junctional reentry
      tachycardia and other supraventricular tachyarrhythmias.
AB  - BACKGROUND: Coronary sinus access by electrode catheters is easier in patients
      with atrioventricular junctional reentry tachycardia (AVJRT) than in patients
      with other supraventricular tachyarrhythmias. The reason for this has not been
      addressed. METHODS AND RESULTS: The size and shape of the proximal coronary sinus
      were measured in 15 patients with AVJRT and 14 control subjects after
      angiographic visualization. Coronary sinus dimensions, morphology, and angle of
      origin from the right atrium were measured. The proximal coronary sinus in
      patients with AVJRT was larger than in the control population. The mean ostium
      diameter was 12.2 +/- 2 mm compared with control dimensions of 8.5 +/- 1.5 mm, P
      = .00001. At a distance of 5 mm from the ostium, the coronary sinus measured 10.2
      +/- 1.8 mm compared with 8.1 +/- 1.9 mm, P = .007. The dilatation persisted 10 mm
      into the coronary sinus, with a measurement of 9 +/- 1.4 mm compared with 7.6 +/-
      2 mm, P = .04. In 73% of AVJRT patients, the proximal coronary sinus had the
      appearance of a wind sock. This morphology was seen only in 7% of control
      patients, in whom the coronary sinus was tubular (in 93%). There was considerable
      interindividual variability in the angle of origin. CONCLUSIONS: The proximal
      coronary sinus in patients with AVJRT was significantly different from a control
      population. The ostium was 44% larger and remained more dilated to at least 10 mm
      from the ostium. The appearance was like a wind sock in AVJRT patients and
      tubular in the control patients. These findings may have important implications
      for arrhythmia pathogenesis in such patients.

PMID- 7634461
TI  - Isolated congenital complete atrioventricular block in adult life. A prospective
      study.
AB  - BACKGROUND: The prognosis of congenital complete atrioventricular block (CCHB) is
      usually considered favorable in adults. This belief is based on studies
      comprising a limited number of patients and with rather short observation times.
      In the present study, the natural history of the disease was investigated by a
      prospective follow-up through decades of adult life of patients with a large
      group having well-defined CCHB without structural heart disease. METHODS AND
      RESULTS: The diagnostic criteria of CCHB proposed by Yater were applied. Patients
      registered as having CCHB in 1964, supplemented by younger patients all without
      symptoms during their first 15 years of life, were selected. The study was
      limited to patients with isolated, complete, permanent block. An interview was
      conducted with all patients and clinical follow-up data obtained. There were
      finally 102 patients, 61 women and 41 men. In November 1994, the time of
      observation, after the age of 15 years in survivors, was between 7 and 30 years.
      The mean age at follow-up or at death was 38 years, median age 37 years, and
      range 16 to 66 years. Stokes-Adams (SA) attacks occurred in 27 patients, in 8
      with a fatal outcome. The first attack was fatal in 6 of these 8 patients.
      Nineteen survived and a pacemaker (PM) was implanted thereafter. Another 8
      patients received a PM because of repeated fainting spells, and 27 others have
      had a PM implanted for other reasons such as fatigue, effort dyspnea, dizziness,
      ectopies during exercise tests, mitral regurgitation, and a low ventricular rate
      (VR). VR decreased with age, with a mean rate at 15 years of 46 beats per minute
      (bpm), at 16 to 20 years of 43 bpm, at 21 to 30 years of 41 bpm, at 31 to 40
      years of 40 bpm, and after 40 years of age of 39 bpm. SA attacks occurred in all
      7 patients with prolonged QTc time. Low VR at rest or at work, presence of bundle
      branch block pattern, low working capacity, and ectopies at rest and/or during
      effort were not statistically significant risk factors. SA attacks occurred in 6
      patients without any of these signs. Mitral regurgitation developed in 16
      patients and 4 died. A PM reduced the risk of death. A change to a lower degree
      of block occurred in 6 patients. CONCLUSIONS: Prophylactic PM treatment is
      recommended even for symptom-free adults with CCHB because of the high incidence
      of unpredictable SA attacks with considerable mortality from first attacks, a
      gradually decreasing VR, significant morbidity, and a high incidence of
      "acquired" mitral insufficiency.

PMID- 7634462
TI  - Transient outward currents in subendocardial Purkinje myocytes surviving in the
      infarcted heart.
AB  - BACKGROUND: Altered electrical activity of subendocardial Purkinje fibers
      contributes to arrhythmias in the 48-hour infarcted canine heart. Changes in the
      transmembrane action potentials of these fibers include marked action potential
      prolongation. The ionic basis for these changes is unknown. METHODS AND RESULTS:
      We used whole-cell voltage-clamp techniques to study 4-aminopyridine (4-AP)
      sensitive voltage-dependent transient outward currents (Ito1) in Purkinje
      myocytes isolated from LV subendocardial (n = 14) and free-running (n = 15)
      bundles of the normal canine heart. Ito1 in these two groups of control cells
      (normal-zone Purkinje cells [NZPCS]) did not differ. NZPCS Ito1 was then compared
      with Ito1 of Purkinje myocytes dispersed from subendocardium of infarcted hearts
      48 hours after total coronary artery occlusion (IZPC48, n = 14). Ito1 amplitude
      and current density were significantly reduced (P < .01) in IZPC48s (1650 +/- 389
      pA, 9 +/- 2 pA/pF) compared with NZPCS (2917 +/- 267 pA, 20.2 +/- 2 pA/pF) at Vt
      = +55 mV, Vh = -60 mV, where Vt is test potential and Vh is holding potential.
      Decay of Ito1 was biexponential in all NZPCS but monoexponential in 71% of
      IZPC48s. Both NZPCS and IZPC48s have a sustained 4-AP-sensitive component (at 250
      ms, Vt = +55 mV: 4 +/- 1 pA/pF, 3 +/- 1 pA/pF, respectively). Ito1 voltage
      dependence of inactivation did not differ between groups. In IZPC48s, recovery of
      Ito1 from inactivation was slowed significantly. Furthermore, significantly more
      Ito1 was seen with rapid pacing in NZPCS (cycle length [CL] 5000 ms = 100%, CL
      1300 ms = 73%, CL 330 ms = 46%) than in IZPC48s (CL 5000 ms = 100%, CL 1300 ms =
      58%, CL 330 ms = 31%). In three IZPC48s, no Ito1 was seen at CL 330 ms.
      CONCLUSIONS: Ito1 plays a major role in normal Purkinje myocyte
      electrophysiology, contributing both a large transient and a sustained component
      that are 4-AP-sensitive. In subendocardial Purkinje myocytes that survive in the
      48-hour infarcted heart, density of Ito1 is markedly reduced and the remaining
      Ito1 showed specific changes in kinetics. The alterations observed in both Ito1
      density and function could contribute to abnormally long transmembrane action
      potentials of these arrhythmogenic Purkinje myocytes of the infarcted heart.

PMID- 7634463
TI  - Noninvasive localization of experimental atherosclerotic lesions with mouse/human
      chimeric Z2D3 F(ab')2 specific for the proliferating smooth muscle cells of human
      atheroma. Imaging with conventional and negative charge-modified antibody
      fragments.
AB  - BACKGROUND: A murine monoclonal antibody designated Z2D3 (IgM) generated against
      homogenized human atherosclerotic plaques was demonstrated to be highly specific
      for proliferating smooth muscle cells. The primary clone subsequently was
      genetically engineered to provide a mouse/human chimeric antibody with human IgG1
      constant region expressed in a rat myeloma cell line. The resulting Z2D3-73.30
      chimeric retained the immunoreactivity relative to the parent Z2D3-IgM and was
      pepsin-digested to yield F(ab')2. 111In-labeled chimeric Z2D3 F(ab')2 was then
      used for noninvasive imaging of experimental atherosclerotic lesions. To improve
      the imaging characteristics, we modified chimeric Z2D3 F(ab')2 fragments to carry
      a high negative charge. Improved visualization of targets with 111In-labeled,
      negatively charged, polymer-modified antibodies most probably is the result of
      faster blood clearance and a decrease in nontarget background activity. METHODS
      AND RESULTS: Experimental atherosclerotic lesions were induced in rabbits by
      deendothelialization of the infradiaphragmatic aorta followed by a 6% peanut oil
      2% cholesterol diet. After 12 weeks, localization of the conventionally labeled
      111In-Z2D3 F(ab')2 (24 Mbq [650 microCi]/500 to 750 micrograms) (n = 4) was
      compared with 111In-labeled, negatively charged, polymer-modified Z2D3 F(ab')2
      (24 Mbq [650 microCi]/25 to 50 micrograms) in eight atherosclerotic rabbits.
      Three control rabbits also received radiolabeled polymer-modified Z2D3. Ten
      rabbits with atherosclerotic lesions received 111In-labeled nonspecific human
      IgG1 F(ab')2 with (n = 6) or without (n = 4) negative charge modification.
      Atherosclerotic lesions were visualized in all rabbits with the conventional Z2D3
      F(ab')2 at 48 hours. However, unequivocal lesion visualization was possible at 24
      hours only with negatively charged, polymer-modified Z2D3 F(ab')2. Quantitative
      uptake of F(ab')2 fragments was essentially determined by the presence of
      atherosclerotic lesions (F1.37 = 69.8; P < .0001) and the specificity of the
      antibody (F1.37 = 36.6; P < .0001). Uptake of the conventional Z2D3 in
      atherosclerotic lesions (mean +/- SEM percent injected dose per gram, 0.112 +/-
      0.024%) was six times higher than background activity in the normal aortic
      segments (nondenuded thoracic aorta; mean percent injected dose per gram, 0.019
      +/- 0.003%). Uptake of the conventional Z2D3 was also significantly higher than
      that of nonspecific human IgG1 F(ab')2 (0.027 +/- 0.004%). Specific uptake of the
      conventional Z2D3 in the lesions was comparable to the charge-modified Z2D3
      uptake (0.084 +/- 0.017; P = .20). Uptake of negative charge-modified Z2D3 in the
      lesions was significantly higher than in the corresponding background activity in
      normal thoracic aorta (0.021 +/- 0.002). Uptake of negative charge-modified Z2D3
      F(ab')2 in the lesions was higher than the uptake of negative charge-modified
      nonspecific IgG1 F(ab')2 (0.020 +/- 0.002) in the lesions. Uptake of charge
      modified Z2D3 in the atherosclerotic lesions was also significantly higher than
      the corresponding regions of the aorta of the control rabbits (0.017 +/- 0.002;
      F1.18 = 27.9; P = .0001). There was, however, no difference in the specific
      lesion uptake of negative charge-modified Z2D3 at 24 hours (0.079 +/- 0.014) and
      48 hours (0.084 +/- 0.0017; P = .99) after intravenous administration. Nontarget
      organ activities were lower with negative charge-modified 111In-labeled Z2D3
      F(ab')2 than with the conventional Z2D3 F(ab')2. Mean kidney activity was
      fourfold less with the modified (0.45 +/- 0.06) than with the conventionally
      radiolabeled (1.67 +/- 0.264; P = .001) Z2D3 F(ab')2.

PMID- 7634464
TI  - Antithrombotic effects of orally active synthetic antagonist of activated factor
      X in nonhuman primates.
AB  - BACKGROUND: Since activated factor X (FXa) has a central role in hemostasis and
      thrombosis, it is an attractive target for antithrombotic strategies.
      Accordingly, we evaluated the relative antihemostatic and antithrombotic effects
      of an orally active amidinoaryl propanoic acid inhibitor of FXa, APAP, in
      baboons. METHODS AND RESULTS: With a two-component thrombogenic device that
      induced the concurrent formation of both arterial-type platelet-rich and venous
      type fibrin-rich thrombus when interposed in chronic exteriorized arteriovenous
      (AV) femoral shunts flowing at 40 mL/min, thrombus formation was compared for
      oral versus parenteral APAP by measurement of 111In-platelet deposition, 125I
      fibrin accumulation, thrombotic obstruction of flow, and circulating levels of
      blood biochemical markers of thrombosis. The direct infusion of APAP (120
      micrograms/min) into AV shunts proximal to thrombogenic devices for 1 hour
      achieved local drug levels of 4.3 +/- 0.4 mg/L and substantially reduced the
      accumulation of platelets and fibrin in the formation of venous-type fibrin-rich
      thrombus (P < .01) but not in the formation of platelet-rich arterial-type
      thrombus (P > .1). APAP was subsequently removed from plasma with plasma
      clearance rates of T50 alpha of 6.3 minutes and T50 beta of 99 minutes. The oral
      administration of APAP (50 mg/kg) produced peak plasma levels of 3.7 +/- 1.4
      micrograms/mL at 30 minutes and gradually declining plasma levels over about 6 to
      8 hours, with bioavailability estimated to be approximately 5% to 12%. Oral APAP
      decreased platelet deposition (P < .01) and fibrin accumulation (P < .05) in
      venous-type thrombus but failed to decrease platelet or fibrin accumulation in
      arterial-type thrombus (P > .1 in both cases). Oral and infused APAP prolonged
      the activated partial thromboplastin time and prevented thrombus-dependent
      elevations in plasma fibrinopeptide A, thrombin-antithrombin III complex, beta
      thromboglobulin, and platelet factor 4 levels. Additionally, APAP produced dose
      dependent inhibition of FXa bound to thrombus on segments of vascular graft
      interposed in exteriorized AV shunts for 15 minutes. CONCLUSIONS: An oral
      synthetic antagonist of FXa, APAP, inhibits the formation of venous-type fibrin
      rich thrombus by inactivating bound and soluble FXa without impairing platelet
      hemostatic function.

PMID- 7634465
TI  - Deleterious effects of a systemic lytic state on reperfused myocardium.
      Minimization of reperfusion injury and enhanced recovery of myocardial function
      by direct angioplasty.
AB  - BACKGROUND: The beneficial effects of flow restoration and the deleterious impact
      of reperfusion injury on ischemic myocardium are well known. However, most
      experimental studies have induced reperfusion by mechanical release of
      nonthrombotic occlusions, only occasionally in the presence of a systemic lytic
      state. Conditions differ markedly in patients undergoing pharmacological or
      mechanical recanalization of thrombotically occluded coronary arteries.
      Accordingly, this study was designed to determine whether the method of coronary
      occlusion and mode of recanalization influence the response of the heart to
      reperfusion. METHODS AND RESULTS: The acute effects of reperfusion on right
      ventricular (RV) function and histology were studied in open-chest dogs subjected
      to right coronary artery (RCA) balloon occlusion and deflation alone (group 1),
      pharmacological lysis of thrombotic occlusions (group 2), balloon occlusion with
      reperfusion induced by balloon deflation in the presence of a systemic lytic
      state (group 3), and recanalization of thrombotically occluded vessels by direct
      angioplasty (group 4). In all groups, 1 hour of RCA occlusion led to RV free wall
      (FW) dyskinesis. In group 1, reperfusion promptly improved RVFW function, with
      normal RVFW thickness and only minimal edema by microscopy. In contrast, in group
      2, clot lysis led to acute RVFW swelling and impaired recovery of RVFW
      contraction associated with striking interstitial edema, contraction band
      necrosis, and hemorrhage by microscopy. In group 3, balloon deflation in the
      presence of a lytic state led to a similar but less severe pattern of abrupt RVFW
      swelling and impaired recovery of RVFW function but lesser histological
      alterations than in group 2. However, mechanical recanalization of thrombotically
      occluded vessels (group 4) led to prompt recovery of RVFW function without
      significant RVFW swelling or histological abnormalities. CONCLUSIONS: Our
      observations indicate that the responses of ischemic myocardium to reperfusion
      are influenced by factors beyond those effects attributable to ischemia and
      reperfusion per se. Pharmacological lysis of coronary thrombi results in
      alterations characteristic of reperfusion injury and associated with impaired
      functional recovery. Such changes are also evident, although to a lesser extent,
      when reperfusion of northrombotic occlusions is induced by mechanical
      recanalization in the presence of a systemic lytic state but not in its absence.
      However, such effects were not seen with direct mechanical recanalization of
      thrombotically occluded vessels. In aggregate, these findings indicate that
      induction of a systemic lytic state, together with products released by lysis of
      intracoronary thrombi, generates an inurious milieu that exerts adverse effects
      on reperfused myocardium.

PMID- 7634466
TI  - Glibenclamide, a selective inhibitor of ATP-sensitive K+ channels, attenuates
      metabolic coronary vasodilatation induced by pacing tachycardia in dogs.
AB  - BACKGROUND: We previously reported that glibenclamide (a selective inhibitor of
      ATP-sensitive K+ channels [K+ATP channels]) inhibited metabolic coronary
      vasodilatation induced by beta 1-adrenoceptor stimulation. However, the role of
      K+ATP channels in metabolic coronary vasodilatation induced by tachycardia is
      still unknown. This study aimed to determine whether glibenclamide attenuates
      metabolic coronary vasodilatation induced by pacing-induced tachycardia. METHODS
      AND RESULTS: In anesthetized dogs, increasing heart rate from 103 +/- 1 to 160
      beats per minute with atrial pacing increased coronary blood flow without
      altering arterial pressure and left ventricular pressure. Intracoronary infusion
      of glibenclamide at 1.5 and 5.0 micrograms.kg-1.min-1 did not alter basal
      coronary blood flow but significantly attenuated (P < .01) the tachycardia
      induced coronary vasodilatation without altering the tachycardia-induced increase
      in myocardial oxygen consumption (MVO2). In conscious dogs, intracoronary
      glibenclamide at 5.0 micrograms.kg-1.min-1 attenuated (P < .05) coronary
      vasodilatation induced by ventricular pacing from 85 +/- 6 to 150 beats per
      minute. Glibenclamide markedly attenuated coronary vasodilation evoked with the
      K+ATP channel opener pinacidil. CONCLUSIONS: These data indicate that blockade of
      coronary vascular K+ATP channels with glibenclamide inhibited metabolic coronary
      vasodilatation induced by pacing tachycardia in dogs, suggesting that K+ATP
      channels are involved in the mechanism mediating metabolic coronary
      vasodilatation associated with pacing tachycardia.

PMID- 7634467
TI  - Dynamics of early postischemic myocardial functional recovery. Evidence of
      reperfusion-induced injury?
AB  - BACKGROUND: The present study was designed to explore the relation between the
      duration of ischemia and the rate and extent of myocardial functional recovery
      after reperfusion. METHODS AND RESULTS: Isolated rat hearts were perfused with
      blood from a support animal for 15 minutes (flow rate, 2.5 mL/min; perfusion
      pressure, 60.1 +/- 1.3 mm Hg). Control left ventricular developed pressure (LVDP)
      was measured, and the hearts (six per group) were subjected to 10, 20, 30, 40,
      50, 60, 70, or 80 minutes of global ischemia (37 degrees C) and 60 minutes of
      reperfusion. Pacing (320 beats per minute) was instituted before and after
      ischemia. In all groups, transient arrhythmias occurred at the onset of
      reperfusion, to be followed by an early phase of recovery that peaked after 2 to
      3 minutes of reperfusion. The relation between the extent of this initial
      recovery and the duration of preceding ischemia was described by a bell-shaped
      curve. Thus, the maximum initial mean recovery after 10, 20, 30, 40, 50, 60, 70,
      or 80 minutes of ischemia was 97%, 108%, 145%, 154%, 118%, 34%, 41%, and 24%,
      respectively, of preischemic LVDP. Possibly indicative of reperfusion-induced
      injury, LVDP then declined in all groups so that after 20 minutes of reperfusion,
      the mean recovery was 63%, 53%, 48%, 50%, 56%, 12%, 9%, and 5%, respectively. In
      the 10-, 20-, 30-, and 40-minute ischemia groups, there then was a secondary
      increase in LVDP, possibly indicating the start of recovery from stunning. After
      60 minutes of reperfusion, the mean recovery of LVDP was 82%, 65%, 59%, 54%, 47%,
      9%, 7%, and 4%, respectively; this second phase of recovery was inversely
      proportional to the duration of ischemia. To define the early phase of recovery
      that had been obscured by reperfusion-induced arrhythmias, we repeated the
      experiments with the inclusion of a cardioplegic infusion (St Thomas' solution
      for 2 minutes before ischemia). This significantly reduced the incidence of
      ventricular fibrillation during early reperfusion. The extent of the initial
      postischemic recovery of LVDP was similar to that observed without cardioplegia;
      however, the mean secondary recovery was greater in all groups. Again, the
      relation of early transient (2 to 5 minutes) recovery to the duration of ischemia
      was represented by a bell-shaped curve, whereas the secondary recovery was
      inversely related. CONCLUSIONS: Although the results of the present study confirm
      the protective properties of cardioplegia, they also shed some light on the
      nature of reperfusion-induced injury and myocardial stunning and their complex
      relation to the severity of the preceding ischemia.

PMID- 7634468
TI  - Electrical activation during ventricular fibrillation in the subacute and chronic
      phases of healing canine myocardial infarction.
AB  - BACKGROUND: Little information is available regarding the effects of myocardial
      infarction on the characteristics of ventricular fibrillation (VF). Epicardial
      activation during VF can be characterized by the cycle length and by the
      characteristics of activation wave fronts. METHODS AND RESULTS: VF was induced by
      programmed stimulation in 6 dogs with subacute healing (1 week) myocardial
      infarction (MI), 5 dogs with chronic (8 week) healing MI, and 6 dogs without MI.
      Using a plaque electrode array with a 2.5-mm interelectrode distance, 112
      electrograms were recorded and 91 vector loops were created for each cycle of VF
      from either the anterior (infarcted) or lateral (noninfarcted) wall. Direction of
      maximum epicardial activation was determined at each site for the first 10 cycles
      of VF (early) and for 10 cycles after 5 seconds of VF (late). Wave front size was
      determined based on a similarity in epicardial activation directions within a
      given area and by a statistical analysis that determined the degree of spatial
      linking at varying distances over the recording plaque. VF cycle length was
      defined as the mean interval of 10 consecutive local activation times.
      Differences among groups and differences between the anterior and posterolateral
      walls were determined by ANOVA. The mean wave front area was significantly larger
      in the presence of subacute MI (97 +/- 4 mm2, early; 78 +/- 3 mm2, late) or
      chronic MI (94 +/- 5 mm2, early; 78 +/- 5 mm2, late) than in noninfarcted animals
      (73 +/- 5 mm2, early; 61 +/- 3 mm2, late). The degree of linking of epicardial
      activation directions was similar in the three groups at distances of 2.5 and 5.0
      mm but was lower at a distance of 7.5 mm among animals without infarction,
      confirming a smaller wave front size and suggesting less organization of
      activation. VF cycle length was significantly longer in the presence of
      infarction (98 +/- 5 ms, normal control animals; 121 +/- 13 ms, subacute MI; 127
      +/- 13 ms, chronic MI). VF cycle length was significantly longer over the
      anterior than the lateral wall in the presence of subacute MI (131 +/- 8 ms,
      anterior; 109 +/- 5 ms, lateral) or chronic MI (136 +/- 9 ms, anterior; 119 +/- 6
      ms, lateral) but not in noninfarcted animals (99 +/- ms, anterior; 97 +/- 5 ms,
      lateral). The prolongation of VF cycle length among animals with infarction was
      associated with slower estimated conduction velocities during VF. CONCLUSIONS:
      During VF, in animals with subacute or chronic healing MI, (1) the size of
      activation wave fronts is larger, (2) the cycle length of VF is longer, (3) the
      conduction velocities are slower, and (4) the degree of organization is greater
      than in control animals. Thus, the characteristics of VF throughout the heart are
      altered by the presence of regional myocardial infarction. The implications of
      these findings for the initiation and maintenance of VF in the presence of
      different underlying myocardial substrates require further study.

PMID- 7634469
TI  - Effects of aortic constriction during experimental acute right ventricular
      pressure loading. Further insights into diastolic and systolic ventricular
      interaction.
AB  - BACKGROUND: Acute right ventricular (RV) hypertension may result in hemodynamic
      collapse. The associated reduction in left ventricular (LV) end-diastolic volume
      is thought to result from reduced RV output (secondary to RV ischemia) and
      adverse direct ventricular interaction. Aortic constriction improves cardiac
      function in these circumstances; this has been attributed to a reversal of the RV
      ischemia caused by an increased coronary perfusion pressure. We hypothesized that
      altered ventricular interaction, potentially via altered septal mechanics, may
      also contribute to the beneficial effects of aortic constriction. METHODS AND
      RESULTS: We instrumented nine dogs with ultrasonic dimension crystals to measure
      RV segment length, septum-to-RV free wall and septum-to-LV free wall diameters,
      and LV anterioposterior diameter. Catheter-tipped manometers were used to measure
      LV and RV pressures. Pericardial pressure was measured with flat, liquid
      containing balloon transducers. Inflatable cuff constrictors were placed on the
      pulmonary artery (PA) and aorta, and a flow probe was placed on the PA. The right
      coronary artery (RCA) was perfused independently by a roller pump calibrated for
      flow. During moderate PA constriction, while RCA pressure was maintained at
      control level, RCA flow did not change significantly (15.8 +/- 6.2 to 16.9 +/-
      11.5 mL/min) and was similar during severe PA constriction (18.6 +/- 9.8 mL/min).
      During severe PA constriction, RV stroke volume decreased from a control value of
      10.3 +/- 4.9 to 2.3 +/- 1.4 mL/beat (P < .05). When aortic constriction was added
      while RCA pressure was maintained at control level, there was an increase in RV
      stroke volume to 4.5 +/- 2.0 mL/beat (P < .05) with no associated change in RCA
      flow (17.8 +/- 9.5 mL/min). However, pressure-dimension loops clearly
      demonstrated changes in diastolic and systolic ventricular interaction; with
      aortic constriction, there was a large increase in the transeptal pressure
      gradient associated with a rightward septal shift. During either isolated severe
      PA constriction or simultaneous severe PA and aortic constriction, RCA flow was
      increased until RCA pressure was approximately equal to that in the aorta. This
      produced an increase in RCA flow of 50% (P < .05); however, this increase in
      coronary flow was ineffective in improving any measure of RV function.
      CONCLUSIONS: In this model of acute RV hypertension, aortic constriction improves
      cardiac function, at least in part, by altering ventricular interaction
      independent of changes in RCA flow. Changes in RCA flow do not appear to have a
      significant impact on cardiac function in this model in which coronary artery
      pressure was maintained at normal or increased levels.

PMID- 7634470
TI  - Early left ventricular dysfunction elicits activation of sympathetic drive and
      attenuation of parasympathetic tone in the paced canine model of congestive heart
      failure.
AB  - BACKGROUND: Although autonomic imbalance is known to be characteristics of
      patients with clinically overt symptomatic congestive heart failure, it is
      currently unknown whether this autonomic response arises early in the course of
      left ventricular dysfunction or is restricted to the later stages of circulatory
      failure. METHODS AND RESULTS: This investigation utilized the technique of
      spectral analysis of heart rate variability in a paced canine model of congestive
      heart failure that permits an examination of autonomic activity at the earliest
      stages of ventricular dysfunction to determine whether early systolic dysfunction
      in congestive heart failure is characterized by autonomic imbalance, which may
      contribute to subsequent myocardial and vascular dysfunction. The results
      indicate that autonomic imbalance as reflected in an abnormal pattern of heart
      rate variability evolves early in the course of ventricular systolic dysfunction
      consisting of both a significant increase in sympathetically influenced low
      frequency heart rate variability and a significant reduction of
      parasympathetically mediated high-frequency variability. This was quantified by a
      marked and significant increase in the area under the low-frequency region from
      0.053 +/- 0.037 (beats per minute)2 at baseline to 0.182 +/- 0.143 (beats per
      minute)2 at 48 hours to 0.253 +/- 0.202 (beats per minute)2 after 7 days of
      pacing (ANOVA, P < .04). The area under the high-frequency region of the curve
      showed a decrease from a baseline value of 0.945 +/- 0.037 (beats per minute)2 to
      0.811 +/- 0.152 (beats per minute)2 at 48 hours to 0.733 +/- 0.197 (beats per
      minute)2 after 7 days of pacing (ANOVA, P < .03). This resulted in a shift in
      autonomic balance away from parasympathetic tone and toward augmented sympathetic
      drive as reflected by the ratio of high- to low-frequency areas from a baseline
      value of 15.2 +/- 9.6 to 10.1 +/- 6.89 at 48 hours and 0.004 +/- 0.001 at 7 days
      (ANOVA, P < .01). CONCLUSIONS: The results indicate that autonomic imbalance as
      reflected in an abnormal pattern of heart rate variability evolves early in the
      course of ventricular systolic dysfunction consisting of both a significant
      increase in sympathetically influenced low-frequency heart rate variability and a
      significant reduction of parasympathetically mediated high-frequency variability.
      The early appearance of these autonomic abnormalities suggests that autonomic
      imbalance plays a significant role in promoting the progression of circulatory
      failure.

PMID- 7634471
TI  - Angiotensin-converting enzyme inhibition and the progression of congestive
      cardiomyopathy. Effects on left ventricular and myocyte structure and function.
AB  - BACKGROUND: Clinical trials have demonstrated that angiotensin-converting enzyme
      inhibition (ACEI) improves survival in patients with long-term left ventricular
      (LV) dysfunction. However, it remained unclear from these clinical reports
      whether the beneficial effects of ACEI were due to direct improvements in LV
      myocardial structure and function. Accordingly, the overall objective of the
      present study was to examine the direct effects of ACEI on both LV and myocyte
      structure and function in the setting of cardiomyopathic disease. METHODS AND
      RESULTS: LV and isolated myocyte function and structure were examined in control
      dogs (n = 6), in dogs after the development of dilated cardiomyopathy caused by
      rapid ventricular pacing (RVP, 216 beats per minute, 4 weeks, n = 6), and in dogs
      with RVP and concomitant ACEI (RVP/ACEI, fosinopril 30 mg/kg BID, n = 6). LV
      ejection fraction fell with RVP compared with control values (35 +/- 3 versus 73
      +/- 2%, P < .05) and was higher with RVP/ACEI compared with RVP values (41 +/-
      4%, P = .048). LV end-diastolic volume increased with RVP compared with control
      values (78 +/- 7 versus 101 +/- 7 cm3, P < .05) and was lower with RVP/ACEI (82
      +/- 3 cm3, P < .05). Isolated myocyte length increased with RVP (182 +- 1 versus
      149 +/- 1 micron), and the velocity of shortening decreased (36 +/- 1 versus 57
      +/- 1 micron/s) compared with control values (P < .05). With RVP/ACEI, myocyte
      length was reduced (169 +/- 1 micron) and velocity of shortening was increased
      (45 +/- 1 micron/s) compared with RVP values (P < .05). Myocyte velocity of
      shortening after beta-adrenergic receptor stimulation with 25 nmol/L
      isoproterenol was reduced with RVP compared with control values (142 +/- 5 versus
      193 +/- 8 micron/s, P < .05) and significantly improved with RVP/ACEI (166 +/- 6
      micron/s, P < .05). In the RVP group, beta-adrenergic receptor density fell 26%,
      and cAMP production with beta-adrenergic receptor stimulation was reduced 48%
      from control values. RVP/ACEI resulted in a normalization of beta-adrenergic
      receptor density and cAMP production. LV myosin heavy-chain content when
      normalized to dry weight of myocardium was unchanged with RVP (149 +/- 11 mg per
      gram dry weight of myocardium [gdwt]) and RVP/ACEI (150 +/- 4 mg/gdwt) compared
      with control values (165 +/- 4 mg/gdwt). LV collagen content decreased with RVP
      compared with control values (7.6 +/- 0.4 versus 9.6 +/- 0.8 mg per gram wet
      weight of myocardium [gwwt], P < .05) but was increased with RVP/ACEI (14.4 +/-
      1.3 mg/gwwt, P < .05). CONCLUSIONS: Concomitant ACEI with chronic tachycardia
      reduced LV chamber dilation and improved myocyte contractile function and beta
      adrenergic responsiveness. Contributory cellular and extracellular mechanisms for
      the beneficial effects of ACEI in this model of dilated cardiomyopathy included a
      normalization of beta-adrenergic receptor function and enhanced myocardial
      collagen support. The results from this study provide evidence that ACEI during
      the development of cardiomyopathic disease provided beneficial effects on LV
      myocyte contractile processes and myocardial structure.

PMID- 7634473
TI  - Electrical resistances of interstitial and microvascular space as determinants of
      the extracellular electrical field and velocity of propagation in ventricular
      myocardium.
AB  - BACKGROUND: In myocardial ventricular tissue, extracellular electrical resistance
      (ro) is an important determinant of propagation velocity (theta) and the
      magnitude of the extracellular bipolar electrogram (delta Vo). The extracellular
      space is composed of two compartments, the vascular space and the interstitial
      space. To assess the electrical equivalent of this compartmentation in the
      ventricular myocardium and its effect on ro, theta, and delta Vo, electrical
      cable analysis was performed in an arterially perfused rabbit papillary muscle.
      METHODS AND RESULTS: Vascular resistivity was changed from 75 to 86 to 143 and to
      221 omega/cm by variation of hematocrit in the perfusate from 0% to 10% to 40%
      and to 60%. As a means to vary the volume of the interstitial space and with this
      as its resistivity, colloid osmotic pressure (COP) in the perfusate was changed
      from 9 to 36 and to 94 mm Hg by altering the dextran concentration in the
      perfusate from 10 to 40 to 80 g/L. Decreasing COP had a marked effect on ro (56%
      decrease), delta Vo (decrease from 61 to 42 mV), theta (increase from 48 to 59
      cm/s), and the diameter of the muscle fiber (increase of 12%). If COP was
      increased from 36 to 94 mm Hg, ro (by 35%) and delta Vo (from 62 to 75 mV)
      increased; theta and diameter showed no significant changes. In contrast,
      alterations of intravascular electrical resistivity in a range from 75 to 221
      omega/cm did not induce any significant changes in ro, delta Vo, theta, and
      diameter of the preparations. CONCLUSIONS: We conclude from our data that (1) the
      microvascular tree in ventricular myocardium is electrically insulated to a large
      degree from the interstitial space and that (2) electrical current flow in the
      extracellular space during excitation is confined to the narrow, anisotropic
      interstitial space.

PMID- 7634472
TI  - A new control volume method for calculating valvular regurgitation.
AB  - BACKGROUND: The purpose of the present study was to develop a new method of
      measuring heart valvular regurgitation based on control volume theory and to
      verify its accuracy in vitro and in vivo. Current methods of quantifying valvular
      regurgitation rely too much on assumptions about the flow field and therefore are
      difficult to apply in vivo. In particular, the proximal isovelocity surface area
      (PISA) method oversimplifies the proximal velocity field by assuming
      hemispherical isovelocity contours proximal to the orifice. This severely limits
      the applicability of the PISA method. Use of the basic control volume theory,
      however, removes the need to assume the manner in which the proximal flow
      accelerates toward the regurgitant orifice, the shape and size of the orifice,
      the shape of the orifice plate, and the non-newtonian behavior of the fluid.
      Apart from a correction that is necessary if the orifice plate is moving, the
      control volume method assumes only the incompressibility of the fluid and
      therefore is a potentially more accurate approach. In addition, the use of
      magnetic resonance imaging (MRI) precludes the need for an acoustic window.
      METHODS AND RESULTS: MRI has been used to measure the three-dimensional velocity
      field proximal to regurgitant orifices, including single and multiple orifices
      and a cone-shaped orifice plate. Both steady (0 to 7.5 L/min) and pulsatile (2
      and 3 L/min) flows were used. By intergrating this velocity over a control volume
      surrounding the orifice, we calculated the flow rate through the orifice. As a
      validation, the cardiac output of a 50-kg pig also was measured and was compared
      with thermodilution measurements. It was found that MRI could be used to measure
      the three-dimensional flow proximal to regurgitant orifices. This enabled the
      calculation of the flow rate through the orifice by integrating the velocity over
      the surface of a control volume covering the orifice. This flow rate correlated
      well with the actual rate (0.992; correlation line slope, 1.01). Care had to be
      taken, however, to exclude from the integration regions of aliased velocity. The
      cardiac output of the pig measured using MRI was in close agreement with the
      themodilution measurements. CONCLUSIONS: Our new method of measuring valvular
      regurgitation has been shown to be very accurate in vitro and in vivo and
      therefore is a potentially accurate way to quantify valvular regurgitation.

PMID- 7634474
TI  - Proarrhythmic response to potassium channel blockade. Numerical studies of
      polymorphic tachyarrhythmias.
AB  - BACKGROUND: Prompted by the results of CAST results, attention has shifted from
      class I agents that primarily block sodium channels to class III agents that
      primarily block potassium channels for pharmacological management of certain
      cardiac arrhythmias. Recent studies demonstrated that sodium channel blockade,
      while antiarrhythmic at the cellular level, was inherently proarrhythmic in the
      setting of a propagating wave front as a result of prolongation of the vulnerable
      period during which premature stimulation can initiate reentrant activation. From
      a theoretical perspective, sodium (depolarizing) and potassium (repolarizing)
      currents are complementary so that if antiarrhythmic and proarrhythmic properties
      are coupled to modulation of sodium currents, then antiarrhythmic and
      proarrhythmic properties might similarly be coupled to modulation of potassium
      currents. The purpose of the present study was to explore the role of
      repolarization currents during reentrant excitation. METHODS AND RESULTS: To
      assess the generic role of repolarizing currents during reentry, we studied the
      responses of a two-dimensional array of identical excitable cells based on the
      FitzHugh-Nagumo model, consisting of a single excitation (sodium-like) current
      and a single recovery (potassium-like) current. Spiral wave reentry was initiated
      by use of S1S2 stimulation, with the delay timed to occur within the vulnerable
      period (VP). While holding the sodium conductance constant, the potassium
      conductance (gK) was reduced from 1.13 to 0.70 (arbitrary units), producing a
      prolongation of the action potential duration (APD). When gK was 1.13, the tip of
      the spiral wave rotated around a small, stationary, unexcited region and the
      computed ECG was monomorphic. As gK was reduced, the APD was prolonged and the
      unexcited region became mobile (nonstationary), such that the tip of the spiral
      wave inscribed an outline similar to a multipetaled flower; concomitantly, the
      computed ECG became progressively more polymorphic. The degree of polymorphism
      was related to the APD and the configuration of the nonstationary spiral core.
      CONCLUSIONS: Torsadelike (polymorphic) ECGs can be derived from spiral wave
      reentry in a medium of identical cells. Under normal conditions, the spiral core
      around which a reentrant wave front rotates is stationary. As the balance of
      repolarizing currents becomes less outward (eg, secondary to potassium channel
      blockade), the APD is prolonged. When the wavelength (APD.velocity) exceeds the
      perimeter of the stationary unexcited core, the core will become unstable,
      causing spiral core drift. Large repolarizing currents shorten the APD and result
      in a monomorphic reentrant process (stationary core), whereas smaller currents
      prolong the APD and amplify spiral core instability, resulting in a polymorphic
      process. We conclude that, similar to sodium channel blockade, the proarrhythmic
      potential of potassium channel blockade in the setting of propagation may be
      directly linked to its cellular antiarrhythmic potential, ie, arrhythmia
      suppression resulting from a prolonged APD may, on initiation of a reentrant wave
      front, destabilize the core of a rotating spiral, resulting in complex motion
      (precession) of the spiral tip around a nonstationary region of unexcited cells.
      In tissue with inhomogeneities, core instability alters the activation sequence
      from one reentry cycle to the next and can lead to spiral wave fractination as
      the wave front collides with inhomogeneous regions. Depending on the nature of
      the inhomogeneities, wave front fragments may annihilate one another, producing a
      nonsustained arrhythmia, or may spawn new spirals (multiple wavelets), producing
      fibrillation and sudden cardiac death.

PMID- 7634475
TI  - In utero placement of aortopulmonary shunts. A model of postnatal pulmonary
      hypertension with increased pulmonary blood flow in lambs.
AB  - BACKGROUND: The development of pulmonary hypertension and its associated
      increased vascular reactivity is a common accompaniment of congenital heart
      disease with increased pulmonary blood flow. Although the morphology of the
      pulmonary vascular changes is well described, the mechanisms of vascular
      remodeling and increased reactivity remain incompletely understood. METHODS AND
      RESULTS: To elucidate these mechanisms, we established an accurate and reliable
      experimental model of pulmonary hypertension with increased pulmonary blood flow.
      An aortopulmonary shunt was created with an 8.0-mm expanded
      polytetrafluoroethylene vascular graft in 11 late-gestation fetal lambs. At 1
      month of age, shunted lambs had a pulmonary-to-systemic blood flow ratio of 2.2
      +/- 1.2. Compared with 11 age-matched control lambs, mean pulmonary arterial
      pressure (44.8 +/- 11.7 versus 16.2 +/- 2.9 mm Hg) and the ratio of pulmonary to
      systemic arterial pressure were significantly increased (P < .05). Pulmonary
      vascular resistance was not significantly increased. The pulmonary
      vasoconstricting response to the infusion of U46619 (a thromboxane A2 mimic) or
      acute alveolar hypoxia also was augmented in the shunted lambs. Morphometric
      analysis of the barium-filled pulmonary artery bed revealed medial hypertrophy,
      abnormal extension of muscle distally into the walls of the intra-acinar
      arteries, and increased numbers of barium-filled intra-acinar arteries.
      CONCLUSIONS: In utero placement of aortopulmonary shunts reproduces the aberrant
      hemodynamic state of children with cogenital heart disease with left-to-right
      shunts; postnatal pulmonary hypertension, increased pulmonary blood flow, and
      vascular remodeling. In addition, the lambs have a unique paradoxical increase in
      pulmonary vascular volume that attenuates an increase in pulmonary vascular
      resistance. This experimental preparation provides a useful and consistent model
      for the study of the pathogenesis of pulmonary hypertension.

PMID- 7634476
TI  - Clinical trials for claudication. Assessment of exercise performance, functional
      status, and clinical end points. Vascular Clinical Trialists.

PMID- 7634477
TI  - Vulnerability of pulmonary capillaries in heart disease.
AB  - The pulmonary blood-gas barrier presents a dilemma. It must be extremely thin for
      efficient gas exchange. However, it also needs to be immensely strong because the
      stresses in the pulmonary capillary wall become extremely high when the capillary
      pressure rises. Stress failure of the capillaries occurs in several pathological
      conditions. It causes high-permeability edema as in neurogenic pulmonary edema or
      high-altitude pulmonary edema; alveolar hemorrhage, which occurs in all galloping
      racehorses; or a combination of the two as in severe congestive heart failure.
      The vulnerability of the capillary wall to increased mechanical stress has not
      previously been sufficiently appreciated.

PMID- 7634478
TI  - Coronary artery screening by electron beam computed tomography. Facts,
      controversy, and future.
AB  - Coronary calcium as detected by electron beam computed tomography always
      signifies at least some atherosclerosis, appears to be correlated with coronary
      risk factors, cardiac history, and overall angiographic severity of disease, but
      is inconsistently related to degree of atherosclerotic lesion stenosis in a given
      artery. Increasing evidence, however, suggests an association between coronary
      artery calcium, atherosclerosis, and coronary risk. But atherosclerosis is a very
      common condition, its prevalence increasing with age. No fully validated method
      for determining the quantity of coronary calcium is available, and we do not know
      whether the amount of calcium is a consistently accurate reflection of the amount
      of atherosclerosis or whether the amount of atherosclerosis reflects the degree
      of risk. Furthermore, the prognostic significance of coronary calcium in any
      given atherosclerotic lesion is not yet established. What is clear from cohort
      studies, however, is that at least three quarters of asymptomatic individuals, at
      least half of whom would have "positive" coronary calcium electron beam computed
      tomographic scans, will live for at least 10 years without cardiac problems of
      any kind. Investigation is needed to determine whether medical intervention may
      impact the clinical outcome of the rest of those identified with a positive scan
      but destined to suffer future clinical events. Despite lack of validation, this
      test has widespread appeal, both to the public as a means of being able to find
      out the condition of their coronary arteries "without injections or dye" and to
      hospitals and private medical groups who view this both as an innovation in
      cardiovascular diagnosis and as a potentially profitable diagnostic
      procedure.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7634479
TI  - Emergence of scientific explanations of nature in ancient Greece. The only
      scientific discovery?

PMID- 7634480
TI  - Lipid lowering, regression, and coronary events. A review of the
      Interdisciplinary Council on Lipids and Cardiovascular Risk Intervention, Seventh
      Council meeting.

PMID- 7634482
TI  - Images in cardiovascular medicine. Circumflex artery aneurysm.

PMID- 7634481
TI  - Coronary plaque disruption.

PMID- 7634483
TI  - Guidelines for Clinical Intracardiac Electrophysiological and Catheter Ablation
      Procedures. A report of the American College of Cardiology/American Heart
      Association Task Force on practice guidelines. (Committee on Clinical
      Intracardiac Electrophysiologic and Catheter Ablation Procedures). Developed in
      collaboration with the North American Society of Pacing and Electrophysiology.

PMID- 7634484
TI  - A scheme for the interpretation of primary and secondary disturbances of plasma
      and urinary amino acid profiles. A possible way to an expert system.
AB  - A general scheme for the interpretation of primary and secondary abnormalities of
      plasma and urine amino acid concentrations is described. The key steps of this
      scheme are: analytical assessment of the measurements, comparison of results
      obtained with the reference values expressed in absolute and/or relative
      concentrations and identification of abnormally increased ninhydrin-positive
      compounds. The interpretation of results takes account of the various
      abnormalities induced by drugs or diet. The origins of these abnormalities are
      ordered by their frequency. A part of the proposed scheme is now computerized as
      the first step in the development of an expert system.

PMID- 7634485
TI  - CSF acetylcholinesterase in Parkinson disease: decreased enzyme activity and
      immunoreactivity in demented patients.

PMID- 7634486
TI  - Cholinesterase activities in cerebrospinal fluid of patients with idiopathic
      convulsive disorders.

PMID- 7634487
TI  - Active and acid-activatable TGF-beta in human sera, platelets and plasma.
AB  - Assays which measure active and latent forms of transforming growth factor beta
      (TGF-beta) separately in human serum and plasma are required to investigate the
      biological role of TGF-beta in a variety of human diseases. We have developed an
      enzyme-linked immunosorbent assay (ELISA) using two polyclonal antibodies against
      TGF-beta which rapidly determines the amount of active plus acid-activatable,
      latent TGF-beta forms ((a+l)TGF-beta) present in human serum and plasma in the
      range 4 pmol/l to 2000 pmol/l. To measure active TGF-beta alone, we have
      developed a second ELISA using the extracellular domain of the TGF-beta type II
      receptor as the capture reagent which detects active TGF-beta in serum and plasma
      samples in the range 20 pmol/l to 4000 pmol/l. Both assays detect TGF-beta 1 and
      TGF-beta 3 with similar sensitivity, are > 10-fold less sensitive to TGF-beta 2
      and are not affected by a range of other peptide growth factors. The mean
      (a+l)TGF-beta present in human serum was 330 pmol/l but the range was very large
      (< 4 pmol/l to 1400 pmol/l). The mean active TGF-beta present was 230 pmol/l
      (range < 20 pmol/l to 1400 pmol/l) and the proportion of the (a+l)TGF-beta
      present which was active [a/(a+l)] varied from < 10% to 100%. The concentration
      of (a+l)TGF-beta and the proportion of TGF-beta which was active were very
      similar in the serum and platelet-poor plasma prepared from the same whole blood
      sample. The clot formed during serum preparation retained all of the TGF-beta
      which was detected by the (a+l)TGF-beta ELISA in the corresponding platelet
      releasate, although the PDGF in platelets was released into the serum. In
      contrast, platelet-poor plasma contained no detectable PDGF demonstrating that
      the (a+l)TGF-beta assayed in the plasma was not due to platelet degranulation
      after bleeding. Serum active TGF-beta and (a+l)TGF-beta concentrations therefore
      provide a reliable estimate of these forms of TGF-beta present in plasma.

PMID- 7634488
TI  - Urinary excretion of N-acetyl-beta-D-glucosaminidase during normal pregnancy.

PMID- 7634489
TI  - Primary focal segmental glomerulosclerosis is associated with increased
      intraglomerular type IV collagen synthesis.

PMID- 7634490
TI  - Serum pyridinolines as specific markers of bone resorption in hemodialyzed
      patients.
AB  - Serum levels of hydroxylysyl pyridinoline and lysyl pyridinoline were quantified
      in uremic patients undergoing maintenance hemodialysis and in healthy subjects.
      Pre-hemodialysis serum levels of hydroxylysyl pyridinoline and lysyl pyridinoline
      in the hemodialyzed patients were significantly higher than those in healthy
      subjects. Serum levels of hydroxylysyl pyridinoline and lysyl pyridinoline
      decreased significantly after hemodialysis with reduction rates of about 40%. Pre
      hemodialysis serum levels of hydroxylysyl pyridinoline and lysyl pyridinoline
      correlated significantly with intact parathyroid hormone, osteocalcin and bone
      specific alkaline phosphatase. Lysyl pyridinoline showed better correlations with
      these parameters than hydroxylysyl pyridinoline. Parathyroidectomy markedly
      decreased serum levels of hydroxylysyl pyridinoline and lysyl pyridinoline. These
      results indicate that serum pyridinolines, especially lysyl pyridinoline, may be
      used as specific biochemical markers of bone resorption in hemodialyzed patients.

PMID- 7634491
TI  - Genetic basis of the silent phenotype of serum butyrylcholinesterase in three
      compound heterozygotes.
AB  - Three Japanese patients showed very low butyrylcholinesterase activity in their
      sera and appeared to be homozygous for silent genes for butyrylcholinesterase.
      From DNA analysis, all three patients were compound heterozygotes: GGA(Gly) to
      CGA(Arg) at codon 365 (G365R) and TTC(Phe) to TCC(Ser) at codon 418 (F418S) in
      patient 1, G365R and CGT(Arg) to TGT(Cys) at codon 515 (R515C) in patient 2 and
      ACT(Thr) to CCT(Pro) at codon 250 (T250P) and AGA(Arg) to TGA(Stop) at codon 465
      (R465X) in patient 3. The K-variant, GCA(Ala) to ACA(Thr) at codon 539, was also
      found in patients 1 and 2. Simple identification methods for all the mutations
      were developed and applied to family analysis and control individuals. The mutant
      alleles (with silent gene and K-variant) were segregated as predicted by theory
      in pedigrees of patients 1 and 2. Four of the mutations, F418S, R515C, T250P and
      R465X, were initially discovered in Japan and genetic heterogeneity among the
      human population for the butyrylcholinesterase gene was suggested.

PMID- 7634493
TI  - A simple and automated HPLC method for determination of total hydroxyproline in
      urine. Comparison with excretion of pyridinolines.
AB  - An HPLC method for measuring total hydroxyproline in human urine was validated.
      Hydroxyproline derivatization was achieved with 9-fluorenylmethyl chloroformate
      after blocking primary amino acids with orthophthaldialdehyde. The derivatives
      (hydroxyproline and internal standard) were separated by reversed phase high
      performance liquid chromatography and detected by absorbance at 254 nm. Duplicate
      measurements of hydroxyproline have a coefficient of variation of 3.9% and the
      recovery in spiked urine samples is between 99.5 and 100.8%. We have compared the
      HPLC procedure with a commercial colorimetric assay. Analytical criteria of these
      methods are identical. Regression analysis, involving 50 samples, shows an
      excellent correlation between hydroxyproline chromatographic (y) and colorimetric
      (x) procedures: y = 0.989x + 2.99 (r = 0.976). Hydroxyproline excretion was
      determined in urine samples from 76 women more than 5 years post-menopause. The
      mean hydroxyproline/creatinine ratio in this group was 19.3 +/- 5.6 mumol/mmol
      (range 10.6-34.7). Finally, we compared in the same urinary samples
      hydroxyproline excretion with pyridinoline excretion (hydroxylysylpyridinoline
      and lysylpyridinoline), a new marker of bone resorption. The values show a
      significant correlation, with r = 0.417 for hydroxylysylpyridinoline and r =
      0.443 for lysylpyridinoline.

PMID- 7634492
TI  - Immunoturbidimetric determination of lipoprotein(a): improvement in the
      measurement of turbid and triglyceride-rich samples.
AB  - Immunoturbidimetry (IT), a widely used method in clinical chemical laboratories,
      was checked for its suitability for lipoprotein(a) (Lp(a)) quantification. When
      the conventional sample diluents were used, turbidimetry gave false results
      particularly with frozen or lipemic sera which correlated poorly with
      electroimmunodiffusion (EID). L-Proline which is known to dissociate Lp(a) from
      other apo B-containing lipoproteins improved the results considerably. One
      hundred frozen sera were investigated in IT with and without the addition of L
      proline to the sample diluent. EID served as a comparison method. In a method
      comparison (IT vs. EID) linear regression analysis improved from r = 0.793: y =
      0.89x - 9.4 (without L-proline) to r = 0.949: y = 0.98x + 4.8 (with L-proline).
      The improvement of the correlation of the two methods was most pronounced in sera
      with triglyceride values exceeding 5.5 mmol/l. The IT assay described here was
      linear between 50 and 1100 mg/l. Total imprecision (coefficient of variation) was
      below 10%. The assay was not affected by the addition of LDL or plasminogen to
      the samples. The Lp(a) concentration of the calibrator, i.e. a secondary standard
      serum, was compared with that of a purified primary Lp(a) standard which
      consisted of a mixture of four apo(a) isoforms. Total Lp(a) mass (lipids,
      protein, carbohydrates) was determined chemically and was compared with the Lp(a)
      mass determined immunochemically by IT and EID. Recovery of the purified Lp(a)
      was 106% (range 90-116%) in IT and 102% (range 91-115%) in EID. Dose response
      curves from pure single isoforms (S1 and S4), calibrator and serum samples were
      parallel. We consider IT to be a simple and rapid method for Lp(a) quantification
      which is not biased by different apo(a) isoforms.

PMID- 7634494
TI  - Comparison of micro-enzymatic and high-performance liquid chromatographic methods
      for the assay of serum 1,5-anhydroglucitol.
AB  - Serum 1,5-anhydro-D-glucitol (AG) has been proposed as a marker of glycaemic
      control in diabetic patients. Two methods have been developed which could be
      applied to routine clinical monitoring of serum AG. We have compared the assay
      characteristics of an adapted enzyme assay, based on the enzyme pyranose oxidase,
      with a high-performance anion-exchange chromatographic method using pulsed
      amperometric detection (HPAEC-PAD). Linearity and minimum detectable
      concentrations were practically identical (to at least 400 mumol/l and 4 mumol/l
      AG, respectively), though intra- and inter-assay precision was better with the
      HPAEC PAD system at a clinically relevant concentration of 40 mumol/l AG (9.8%
      vs. 11.8% and 9.2% vs. 13.0%, respectively). The recovery of added AG to serum
      samples was lower with the micro-enzyme assay than the HPAEC-PAD assay (74 +/-
      15% vs. 102 +/- 8%). Despite good agreement by linear regression (r = 0.974, P <
      0.005), the assay methods did not demonstrate satisfactory agreement when using a
      difference plot (limits of agreement -16.1 to 18.7 mumol/l). We conclude that
      although both assay methods are applicable to routine analyses, the HPAEC-PAD is
      more precise and is more specific for AG than the enzyme based assay.

PMID- 7634495
TI  - Current evidence for and against the TSH receptor being the common antigen in
      Graves' disease and thyroid associated ophthalmopathy.

PMID- 7634496
TI  - Somatostatin receptor scintigraphy and octreotide treatment in patients with
      thyroid eye disease.
AB  - OBJECTIVE: Octreotide, a potent long-acting synthetic somatostatin analogue, has
      been reported to have a beneficial effect in thyroid eye disease (TED), but the
      precise mechanism of action remains unexplained. 111In-DTPA-D-Phe1-octreotide
      (Octreoscan-111) has been used to localize a number of endocrine tumours and
      visualize somatostatin receptors in the retrobulbar tissue of patients with TED.
      Furthermore, this technique can predict the inhibitory effect of octreotide on
      hormone secretion by endocrine tumours, as there is a close relation between the
      clinically observed inhibition and visualization of the tumour using Octreoscan
      111. The aims of the present study were to confirm the beneficial effect of
      octreotide in patients with TED, to investigate the presence of somatostatin
      receptors in the orbital area and also, if possible, to ascertain whether this
      technique could select those patients with TED who might benefit from treatment
      with octreotide. DESIGN: A prospective study. SETTING: An endocrine clinic of a
      national hospital. PATIENTS: Twenty treated thyrotoxic patients with TED, 5
      treated thyrotoxic patients without TED and 5 normal individuals were studied. In
      12 patients with TED, 5 without TED and 5 normal individuals, Octreoscan-111
      scintigraphy of the orbits was performed. The remaining 8 patients with
      ophthalmopathy served as controls. In patients with TED who were investigated
      with Octreoscan-111, 300 micrograms octreotide daily was given for 12 weeks.
      RESULTS: Six patients in both eyes and one patient in one eye showed an
      improvement in ocular manifestations as assessed by clinical criteria and changes
      in the NOSPECS score, while the rest showed no improvement. The patients who
      showed an improvement had a high number of somatostatin receptors and positive
      orbital scans, while with one exception the patients who did not respond had a
      low number of receptors and negative orbital scans (P < 0.02). None of the 5
      patients without TED nor the normal individuals had a positive orbital scan.
      Seven out of 8 control patients with TED showed no change in the disease during
      the trial, while 1 deteriorated. CONCLUSIONS: We conclude that octreotide has a
      beneficial effect in thyroid eye disease and that Octreoscan-111 could predict
      those patients with thyroid eye disease who might benefit from this treatment.

PMID- 7634497
TI  - Multicentre study on prevalence of endocrine complications in thalassaemia major.
      Italian Working Group on Endocrine Complications in Non-endocrine Diseases.
AB  - OBJECTIVE: Thalassaemia major is a common and serious medical problem, worldwide.
      However, there are few data concerning the various endocrine disorders which
      occur in this condition. We have surveyed 25 Italian centres in order to
      establish the prevalences and times of onset of endocrine disorders in patients
      with beta-thalassaemia major. PROJECT AND PATIENTS: A questionnaire specifically
      designed to investigate the prevalences of endocrinopathies was sent to 25
      paediatric and haematology departments. The following data were recorded in the
      questionnaire: sex, age, height and weight, pubertal status according to Tanner's
      classification, history of secondary amenorrhoea, type of endocrinopathy and
      hormone levels at diagnosis, associated complications, serum ferritin level,
      liver enzymes (ALT) and compliance with treatment. RESULTS: An analysis of data
      from 1861 patients showed that failure of puberty was the major clinical
      endocrine problem and was present in 51% of boys and 47% of girls, all over the
      age of 15 years. Secondary amenorrhoea was recorded in 23% of patients (mean age
      18.3 years), primary hypothyroidism in 6.2% (mean age 15.8 years), insulin
      dependent diabetes mellitus in 4.9% (mean age 18.1 years) and hypoparathyroidism
      in 3.6% of the patients (mean age 18.7 years). At present, the majority are in
      the second or third decades of life. The prevalences of hypothyroidism, insulin
      dependent diabetes mellitus and hypoparathyroidism differed in the various
      centres, whereas the frequency of pubertal disorders was very similar.
      CONCLUSIONS: Our study has demonstrated several points. Endocrine evaluation in
      thalassaemic patients must be carried out regularly, especially in those patients
      over the age of 10 years with iron overload and poor compliance with chelation
      therapy. The prevalences of some complications, such as insulin dependent
      diabetes and hypothyroidism, were lower than previously recorded. Hence, it is to
      be hoped endocrine complications will be less common in the future, for patients
      who have started chelation therapy during the first years of life. Because of the
      improved survival of thalassaemic patients with insulin dependent diabetes, and
      the high incidence of multiple endocrine complications, it is important to carry
      out careful follow-up studies for the early detection of any other associated
      complications to facilitate correct treatment.

PMID- 7634498
TI  - Short stature in homozygous beta-thalassaemia is due to disproportionate truncal
      shortening.
AB  - BACKGROUND AND OBJECTIVE: Growth failure in homozygous beta-thalassaemia has been
      recognized for many years, and has persisted despite major treatment advances. In
      this cross-sectional study, sitting and standing height were measured to
      determine whether growth failure was disproportionate. DESIGN: Patient data were
      analysed in three age groups, 2-10 years, 11-18 years and 19 and over. Sitting
      height and subischial leg length were also determined in a cohort of parents (n =
      19) and normal Greek adolescents (n = 32). PATIENTS AND MEASUREMENTS: Of the
      known 156 patients with homozygous beta-thalassaemia in the State of Victoria,
      154 (98.7%) attend our institution. Sitting and standing heights were measured,
      using Harpenden stadiometers, in 57 of 60 (95%) patients aged 2-18 years and in a
      random selection of 51 of 89 patients aged 19 and over (57%). Measurements are
      expressed as mean +/- SDS. Other data analysed included serum concentrations of
      ferritin, zinc, copper, FSH, LH, oestradiol and testosterone, according to
      standard laboratory assays, together with pubertal status and bone age in
      patients aged less than 19 years. RESULTS: Standing height standard deviation
      scores in the 2-10 age group were -0.687 +/- 0.861 (n = 9), in the 11-18 age
      group were -1.838 +/- 1.413 (n = 48) and in the age group 19 and over were -1.175
      +/- 1.126. In individuals aged 2-10 years, sitting height standard deviation
      scores (SDS) were -1.56 +/- 1.02, in individuals 11-18 years were -3.76 +/- 1.51
      (n = 48), and in individuals 19 years and over were -2.77 +/- 1.20 (n = 51),
      compared with subischial leg length SDS which were, in individuals aged 2-10
      years 0.214 +/- 0.91; in 11-18 years, -0.063 +/- 1.347, and in individuals 19 and
      over, 0.37 +/- 1.18. These data show that the reduction in standing height was
      the result of truncal shortening. Mean sitting height SDS was significantly lower
      in children with homozygous beta-thalassaemia, compared with their parents (P <
      0.001), and in a subgroup of Greek adolescents with homozygous beta-thalassaemia
      compared with age and sex matched normal Greek adolescents (P < 0.001). No
      correlation was found between truncal shortening and other clinical and
      biochemical variables measured. CONCLUSIONS: Short stature in our patients with
      homozygous beta-thalassaemia is due to disproportionate truncal shortening. The
      aetiology of truncal shortening in this patient group is likely to be
      multifactorial, although hypogonadism and chelation therapy may be contributory
      factors.

PMID- 7634499
TI  - Effectiveness of a long-acting injectable form of bromocriptine in patients with
      prolactin and growth hormone secreting macroadenomas.
AB  - OBJECTIVE: With the development of new long-acting depot preparations of
      bromocriptine (bromocriptine LAR), we investigated the effectiveness of
      intramuscular injections of long-acting bromocriptine in patients with prolactin
      and GH secreting macroadenomas. STUDY DESIGN AND PATIENTS: Fourteen patients with
      PRL secreting (8 patients) and GH secreting (6 patients) macroadenomas were
      treated with monthly intramuscular injections of a long-acting and repeatable
      form of bromocriptine for 3-6 months. A 50-mg monthly dose was administered in
      the majority of patients with PRL secreting macroadenomas. A 100-mg monthly dose
      was administered in all patients with GH secreting macroadenomas. MEASUREMENTS:
      Plasma PRL and/or GH levels were measured 6 and 12 hours after the first
      injection and then on days 1, 2, 14 and 28 after each injection, up to a maximum
      period of 6 months. Patients were hospitalized for 48 hours after each injection
      and were specifically questioned with respect to side-effects. Pituitary imaging
      with MRI or CT scans was performed in all patients before commencing treatment
      and was subsequently repeated in 5/8 patients with macroprolactinomas and 5/6
      patients with GH secreting macroadenomas after the completion of a 6-month course
      of treatment. RESULTS: In all patients with macroprolactinomas, serum PRL levels
      decreased significantly after their first 50-mg injection with nadir levels
      obtained by 24-48 hours post injection (12815 +/- 8704 vs 1480 +/- 1859 mU/l;
      mean +/- SD, P < 0.01). At their latest follow-up, on a 50-mg monthly dose, 4
      patients developed normoprolactinaemia (PRL levels < 360 mU/l) while two patients
      demonstrated a significant reduction in serum PRL levels (70 and 87% or
      pretreatment values). In two patients, although a substantial decrement of serum
      PRL levels was achieved 12-24 hours post injection, serum PRL levels increased to
      pretreatment values by day 14 post injection. Both patients received a higher
      (100 mg) monthly dose which was partially effective in one patient. In two
      patients with GH secreting macroadenomas, a sustained decrease of elevated GH
      levels was observed; in two patients, while a substantial reduction of the
      elevated serum GH levels was achieved 12-24 hours after the first and subsequent
      injections, serum GH levels increased to pretreatment values by day 14 post
      injection; in two patients there was no effect on the elevated serum GH levels.
      Significant tumour shrinkage (24-50%) was observed in 5/5 patients with PRL
      secreting macroadenomas assessed at completion of a 6-month course of treatment.
      Significant tumour shrinkage was also documented in 2/5 acromegalics tested (29
      and 46% respectively). CONCLUSION: It is concluded that bromocriptine LAR is an
      effective treatment in the majority of patients with macroprolactinomas; it is
      also partially effective in some patients with GH secreting macroadenomas.

PMID- 7634500
TI  - The prevalence of polycystic ovaries in the hepatic glycogen storage diseases:
      its association with hyperinsulinism.
AB  - OBJECTIVE: There has been much debate concerning the relative contribution of
      insulin resistance to the development of polycystic ovaries (PCO). We therefore
      aimed to assess ovarian morphology and insulin/androgen status in females with
      the hepatic glycogen storage diseases types Ia (GSD-Ia) and III (GSD-III),
      disorders associated with abnormalities of insulin secretion. DESIGN: A cross
      sectional study of ovarian ultrasonography, oral glucose tolerance tests (oGTTs)
      and single measurements of gonadotrophins and androgens were performed. PATIENTS:
      Twenty-seven patients were evaluated: 13 with GSD-Ia, median age 11.2 years
      (range, 3.3-26.7) and 14 with GSD-III, aged 13.2 years (4.2-31.3). None had
      clinical signs of hyperandrogenism and only two of the 13 adults (15%) had
      menstrual irregularities. They were compared to 9 normal adult female controls,
      aged 21-28 years. MEASUREMENTS: Ovarian morphology and volume were measured.
      Blood glucose and plasma insulin concentrations were measured at the beginning
      and end of a 2-hour oGTT. Single measures of LH, FSH, testosterone,
      dehydroepiandrosterone sulphate, androstenedione, IGF-I and SHBG were made on
      samples taken at the beginning of the oGTT. RESULTS: In both GSD-Ia and III, all
      those older than 4.8 years of age had a polycystic ovarian appearance. Pre
      pubertal GSD-Ia patients had lower basal and 2-hour blood glucose and plasma
      insulin concentrations than pre-pubertal GSD-III patients. In adults with GSD-Ia
      and GSD-III, although basal and 2-hour blood glucose concentrations did not
      differ, both basal and 2-hour plasma insulin concentrations were significantly
      higher than controls. Serum gonadotrophins, androgens, IGF-I and SHBG were mostly
      normal. CONCLUSIONS: A polycystic ovarian appearance is a common finding in
      patients with glycogen storage disease even before puberty. In GSD-III and adults
      with GSD-Ia, this ovarian appearance was associated with hyperinsulinism,
      suggesting an aetiological link, but this was not the case in pre-pubertal
      children with GDS-Ia. Inborn errors of carbohydrate metabolism may act as useful
      models for examining control mechanisms of ovarian physiology and development.

PMID- 7634501
TI  - Urinary pyridinoline and deoxypyridinoline excretion in children.
AB  - OBJECTIVE: There are few data on urinary markers of collagen breakdown in
      children. We have determined a normal range for urinary pyridinoline and
      deoxypyridinoline in children, assessed the variability in excretion in
      individual children and examined the effect of GH treatment on the excretion of
      these collagen cross-links. DESIGN: A cross-sectional study of a group of healthy
      children and sequential samples from children receiving GH treatment. PATIENTS:
      One hundred and nine healthy children aged 2-15 years, 8 healthy children aged 4
      11 years and 4 children receiving GH treatment. MEASUREMENTS: Total pyridinoline
      and deoxypyridinoline excretion were measured by high performance liquid
      chromatography after initial acid hydrolysis and cellulose extraction steps.
      Serum parathyroid hormone was measured using a two-site immunoradiometric assay
      and urinary hydroxyproline by Ehrlich's reaction using a colorimetric assay.
      Pyridinoline and deoxypyridinoline excretion were expressed as a ratio against
      urine creatinine. RESULTS: High excretion of pyridinoline (Pyr) and
      deoxypyridinoline (DPyr) was seen at all ages with no apparent relation to age
      (mean Pyr/Cr 115 nmol/mmol and DPyr/Cr 31 nmol/mmol). No correlation was found
      with serum parathyroid hormone or urinary hydroxyproline excretion. Marked day to
      day variation was seen in individual children. A progressive rise in excretion
      was seen in children receiving GH treatment with no significant correlation to
      height velocity. CONCLUSIONS: There is a high excretion of the pyridinium cross
      linking amino acids in children of all ages compared to adults. However, a high
      variability exists in single morning urine samples which will limit the
      usefulness of these markers in growing children.

PMID- 7634502
TI  - Characteristics of adults who wish to enter a trial of growth hormone
      replacement.
AB  - OBJECTIVE: It is possible that the degree of perceived well-being may influence
      the decision of an adult with GH deficiency to receive GH replacement. We have
      therefore sought factors which influenced whether or not such a patient wished to
      enter a study of GH replacement. DESIGN: Biochemical, anthropometric and
      demographic characteristics, and well-being, of patients who chose to enter a 12
      month study of GH replacement at Christie Hospital NHS Trust were compared with
      those of patients who declined to enter the study. PATIENTS: Sixty-five adults
      with GH deficiency who entered a study of GH replacement and 33 adults with GH
      deficiency who were approached but who declined to enter the study. MEASUREMENTS:
      The two groups of patients were compared according to sex, age, height, weight,
      body mass index, peak serum GH response to provocative testing, estimated
      duration of GH deficiency, whether GH deficiency was of childhood or adult onset,
      presence or absence of additional pituitary hormone deficiencies, aetiology of GH
      deficiency, previous therapeutic interventions, employment status, marital status
      and living arrangement (65 entered vs 33 declined to enter). Well-being or
      distress was measured using the Nottingham Health Profile (NHP) (65 entered vs 20
      declined to enter) and the Psychological General Well-being Schedule (PGWBS) (33
      entered vs 19 declined to enter). RESULTS: Those who entered the study had
      significantly higher scores on the energy (P = 0.03) and emotional reaction (P =
      0.02) subsections and on the total score (P = 0.04) of the NHP, indicating
      greater distress, and had a significantly lower score (P = 0.009) on the vitality
      subsection of the PGWBS, again indicating greater distress. Those who entered the
      study had a significantly lower prevalence of non-functioning pituitary adenoma
      (P = 0.02) but there was no other difference in biochemical, anthropometric or
      demographic characteristics between the two groups. CONCLUSION: Adults who enter
      a study of GH replacement exhibit greater distress on questionnaire assessment
      than those who decline to enter such a study. This bias must be considered when
      interpreting studies of the effect of GH replacement on well-being in adults.

PMID- 7634504
TI  - Effect of growth hormone replacement on bone mass in adults with adult onset
      growth hormone deficiency.
AB  - OBJECTIVE: Previous studies of the effect of GH replacement on bone mass in
      adults with GH deficiency have produced conflicting results. We have studied the
      effect of 6 and 12 months of GH replacement on bone mass in adults with adult
      onset GH deficiency. DESIGN: Double blind placebo controlled study of GH
      replacement (0.125 IU/kg/week for the first month and 0.25 IU/kg/week thereafter)
      for 6 months and an open study for a further 6 or 12 months. PATIENTS: Twenty-two
      adults (10 men, 12 women), aged 41.5 +/- 2.1 years (mean +/- SE, range 23.6
      59.5), with adult onset GH deficiency. MEASUREMENTS: Single-energy quantitative
      computed tomography was used to measure vertebral trabecular bone mineral density
      (BMD), single-photon absorptiometry (SPA) was used to measure forearm cortical
      and integral bone mineral content and BMD and dual-energy X-ray absorptiometry
      (DXA) was used to measure lumbar spine, femoral neck, trochanteric and Ward's
      triangle integral BMD. RESULTS: After 6 months of GH replacement (n = 21) there
      was a significant decrease in forearm cortical BMD (SPA: median change -0.009
      g/cm2, P = 0.01), forearm integral BMD (SPA: median change -0.016 g/cm2, P =
      0.03), lumbar spine BMD (DXA: median change -0.22 g/cm2; P = 0.003) and femoral
      neck BMD (DXA: median change -0.029 g/cm2, P = 0.006). After 12 months of GH
      replacement (n = 13) there was a significant decrease in lumbar spine BMD (DXA:
      median change -0.035 g/cm2, P = 0.002) from baseline. There was no significant
      increase in bone mass at any site after 6 or 12 months of GH replacement. Change
      in bone mass was not influenced by sex of the patient or by presence or absence
      of additional pituitary hormone deficiencies. CONCLUSION: The response of bone
      mass to 6 and 12 months of GH replacement in adults with adult onset GH
      deficiency is disappointing. Longer-term studies are required to determine
      whether prolonged GH replacement has a beneficial effect on bone mass.

PMID- 7634503
TI  - The growth and cardiovascular effects of high dose growth hormone therapy in
      idiopathic short stature.
AB  - OBJECTIVE: It is possible that high dose GH treatment may have beneficial effects
      on growth but important adverse effects on cardiac function. We have therefore
      investigated the efficacy and cardiovascular effects of high dose biosynthetic
      human GH (r-hGH) treatment in children with idiopathic short stature and a normal
      pretreatment height velocity. STUDY DESIGN: Randomized controlled study.
      PATIENTS: Twenty-nine short (height SDS < 1.5), normally growing (height velocity
      SDS > -1.5), prepubertal children referred to two specialist growth clinics.
      INTERVENTIONS: Children were randomly assigned to an observation group or to
      receive 'standard' (20 IU/m2/week) or 'high' (40 IU/m2/week) dose r-hGH by daily
      subcutaneous injection. At the end of 1 year the observation group were randomly
      assigned to 'standard' or 'high' dose r-hGH therapy for the second year of the
      study. Regular growth, biochemical and echocardiographic monitoring were
      performed throughout the study period. MAIN OUTCOME MEASURES: Changes in height
      velocity, HtSDS for bone age (HtSDSBA), left ventricular mass index (LVMI) and
      left ventricular function (fractional shortening) during 2 years treatment.
      RESULTS: Twenty-seven children completed the study. Ht velocity SDS increased
      with r-hGH therapy in a dose dependent fashion. First-year height velocity SDS
      was +5.7 in the high dose r-hGH group compared with +2.7 in the standard dose r
      hGH group and -0.5 in the observation group (P < 0.001). In those children
      treated for 2 years HtSDSBA was -0.5 in the high dose group but had not changed
      significantly in the standard dose group (-1.7) (P = 0.01). After one year r-hGH
      treatment LVMI was 71 g/m2 (observation group), 73 g/m2 (20 IU/m2/week group) and
      74 g/m2 (40 IU/m2/week group) (P = 0.77). LVMI increased significantly from
      baseline to 76 g/m2 after 2 years therapy with 40 IU/m2/week r-hGH (P = 0.04) but
      nevertheless remained within the normal range. Fractional shortening did not
      change significantly over 2 years of r-hGH therapy. CONCLUSIONS: High dose (40
      IU/m2/week) r-hGH treatment of children with idiopathic short stature resulted in
      a greater short-term acceleration in growth rate than 'standard' dose therapy
      without an excessive advance in skeletal maturity and probably represents the
      optimal growth promoting dose for short, normally growing children. Whether
      continued high dose r-hGH therapy increases final height requires further study.
      Left ventricular morphology and function remained within the normal range during
      r-hGH therapy but regular monitoring of cardiovascular status should continue in
      non-GHD children receiving r-hGH in high doses over a longer time period.

PMID- 7634505
TI  - Dysfunction of the growth hormone/insulin-like growth factor-I axis in women with
      polycystic ovarian syndrome.
AB  - OBJECTIVE: Although a defect in GH regulation has been suggested in women with
      polycystic ovarian syndrome (PCOS), the data are limited and mechanism obscure.
      We have assessed the function of the GH/IGF-I axis in women with PCOS by
      measuring basal IGF-I levels and the ability of the pituitary to secrete GH
      following dopamine and GHRH. DESIGN: For each woman the complete study lasted 3
      days. On the 1st and 2nd days, saline (0.9%, 5 ml/h for 3 h) and dopamine (4
      micrograms/kg/min for 3 h) infusion tests were performed, respectively, in all
      PCOS and control women. Blood samples for GH measurement were obtained before and
      at 20-minute intervals for 3 hours. On the 3rd day a GHRH test (100 micrograms,
      i.v. bolus) was performed in 9 of the women with PCOS and in 9 controls. Blood
      samples for GH measurements were obtained before and at 20-minute intervals for 3
      hours. Basal IGF-I levels were measured in the basal blood samples from the
      saline infusion test in all patients studied. SUBJECTS: Thirteen women with PCOS
      and 11 normally menstruating women (control group), aged 18-35 years, were
      studied. All women with PCOS had hirsutism and oligomenorrhoea since menarche,
      elevated serum values of at least one ovarian androgen and the typical ultrasound
      appearance of PCOS. RESULTS: Growth hormone releasing hormone (GHRH) induced a
      significant increase in GH secretion in both control and PCOS groups. However,
      the GH response to GHRH was found to be significantly lower in women with PCOS.
      The 3-hour infusion of dopamine induced a significant increase in GH levels only
      in the control group, while it failed to stimulate GH release in the women with
      PCOS. Although both dopamine and GHRH failed to induce a normal GH response in
      women with PCOS, their IGF-I levels did not differ significantly from those
      observed in control women. CONCLUSIONS: The diminished GH responses to both GHRH
      and dopamine in women with PCOS, in the presence of normal circulating IGF-I
      levels, suggests a dysregulation in GH secretion. Although the data are
      suggestive of a hypothalamic defect, further studies are required to clarify the
      underlying mechanism and the role, if any, of GH in the pathogenesis of
      polycyctic ovarian syndrome.

PMID- 7634506
TI  - A simplified gonadotrophin-releasing hormone test for precocious puberty.
AB  - BACKGROUND AND OBJECTIVE: The gonadotrophin-releasing hormone (GnRH) test is
      important for the evaluation of children with disorders of puberty.
      Traditionally, the test determines the peak LH and the peak FSH responses from 5
      to 8 blood samples, which makes it cumbersome and costly. We suspected that the
      test could be simplified to require fewer hormonal measurements. DESIGN: A
      retrospective clinical study. PATIENTS: Subjects were 44 girls and 7 boys with
      signs of precocious puberty, of whom 39 were diagnosed as definite central
      precocious puberty. Fifty-five diagnostic tests and 39 tests for suppression
      during GnRH-analogue treatment were reviewed. MEASUREMENTS: LH and FSH were
      measured in serum samples obtained during a standard GnRH test. PARAMETERS: LH
      and FSH responses and the LH:FSH ratio at 30, 45 and 60 minutes, and the
      respective peak levels. For each parameter, the sensitivities and specificities
      were estimated and the receiver operating characteristic curve was constructed.
      RESULTS: The receiver operating characteristic curves for the LH responses at 30,
      45 and 60 minutes and peak, were similar and showed high specificities and
      sensitivities for the diagnosis of central precocious puberty. A single LH cut
      off (15 IU/I) had diagnostic sensitivity > 90% and specificity > 80% for LH
      concentrations at 30, 45 or 60 minutes and peak, and sensitivity > 90% to detect
      suppression. Calculations of the LH:FSH ratio did not improve the diagnostic
      accuracy of the GnRH test achieved by LH alone. CONCLUSIONS: A single LH
      determination 30 minutes after GnRH administration is as useful as the peak LH;
      FSH measurements are unnecessary for the differential diagnosis of central
      precocious puberty. We propose that for the diagnosis of central precocious
      puberty and for treatment monitoring, the GnRH test to be simplified to LH
      measurement in a single blood sample at 30 minutes.

PMID- 7634507
TI  - Precocious puberty.

PMID- 7634509
TI  - Acute pre-tibial myxoedema following radioiodine therapy for thyrotoxic Graves'
      disease.
AB  - A 54-year-old woman was treated with an oral dose of 555MBq of 131I radioiodine
      for thyrotoxicosis. She had no clinically detectable extrathyroidal
      manifestations of Graves' disease at the time, but within two months developed
      moderately severe ophthalmopathy and very extensive thyroid dermopathy affecting
      her face, arms, hands and feet, in addition to the classic pre-tibial area.
      Although she developed mild post radioiodine hypothyroidism, this was detected at
      an early stage and its treatment had no effect on the extrathyroidal signs.
      Thyrotrophin receptor antibodies (TRAb) were positive before treatment (22%
      inhibition of TSH binding in neat serum), rose to very high levels following
      radioiodine (97.6% inhibition), and fell progressively over the following year
      during treatment with prednisolone. Thyroglobulin autoantibodies became
      detectable following radioiodine but thyroid peroxidase antibodies were
      undetectable throughout. Serum and purified IgG from blood samples obtained prior
      to steroid therapy and over the subsequent year were tested on a dermal
      fibroblast cell line in vitro for the stimulation of synthesis of
      glycosaminoglycans, protein and DNA, but no increase in radiolabel incorporation
      was apparent for any sample when compared to controls. The temporal relation
      between the radioiodine and the acute onset of dermopathy and ophthalmopathy,
      together with the abrupt rise in TRAbs, indicates a probable causal association.
      However, the absence of in-vitro fibroblast stimulation would suggest that the
      pathogenesis of Graves' dermopathy is not dependent solely on any simple humoral
      factor.

PMID- 7634508
TI  - Thyroid cancer management.
AB  - OBJECTIVE: Thyroid cancer is the commonest endocrine malignancy, yet management
      remains controversial. Many endocrinologists advocate diagnosis by fine needle
      aspiration (FNA), treatment by thyroidectomy, ablative radioiodine (131I) and TSH
      suppression, together with follow-up with 131I scans or thyroglobulin (Tg)
      measurements. 131I (therapy or diagnosis) is given only when TSH is > 30 mIU/I.
      With this strategy in mind, the aim of the present study was to audit existing
      clinical practice in a large Edinburgh teaching hospital to establish whether a
      need existed for local guidelines for the management of thyroid cancer. DESIGN
      AND PATIENTS: Retrospective case-note audit of 46 patients, aged 55 (range 26-86)
      years, admitted between 1988 and 1993 with a diagnosis of thyroid cancer.
      RESULTS:  DIAGNOSIS: Our FNA false negative rate was high (13%), aspiration
      technique varied considerably, and cytological reporting was not standardized.
      TREATMENT: Three (11%) patients received 131I despite suboptimal TSH levels
      because of poorly developed mechanisms to prevent this, and 7 (25%) patients had
      inadequate suppression of TSH as a result of poor interspecialty communication.
      FOLLOW-UP: Three (11%) patients were scanned despite TSH levels < 30 mIU/I, and
      in 5 (18%) Tg checks were incomplete. CONCLUSIONS: This audit identifies several
      shortcomings from what might be considered optimum management of thyroid cancer;
      practice was far from uniform even among the endocrinologists within a single
      hospital and interdisciplinary communication was poor. A locally agreed and
      implemented protocol should address most of these problems and improve the care
      of thyroid cancer patients.

PMID- 7634512
TI  - Should prophylactic antibiotics be used in the management of cerebrospinal fluid
      rhinorrhoea following endoscopic sinus surgery? A review of the literature.
AB  - This review article investigates whether prophylactic antibiotics should be used
      in the management of cerebrospinal fluid rhinorrhoea following endoscopic sinus
      surgery. A medline database was used to retrieve all English articles from 1970
      to the present, cross-indexing cerebrospinal rhinorrhoea, antibiotics and
      endoscopic sinus surgery. All relevant articles retrieved were reviewed together
      with their bibliographies. The use of prophylactic antibiotics is neither
      recommended nor condemned by evidence of efficacy. However, their use is
      cautioned against by evidence of a subsequent change in nasopharyngeal flora to
      potentially more invasive organisms. The review concludes that, at present, it is
      usually justifiable to withhold prophylactic antibiotics and to observe for the
      symptoms and signs of meningitis instituting antibiotic therapy when this
      complication develops.

PMID- 7634510
TI  - Clinical and genetic changes in a case of a Cushing's carcinoma.
AB  - A 30-year-old presented in 1984 with a clinically nonfunctional tumour which
      subsequently developed into a metastatic corticotrophinoma from which he died
      despite surgery in 1984, 1986 and 1991 and external radiotherapy in 1986.
      Molecular genetic analysis of tumour and metastatic tissue revealed loss of
      heterozygosity at loci on the autosomes 1p, 3p, 10q26, 11q13 and 22q12. Tissue
      taken at surgery in 1986 also revealed positive cytoplasmic immunostaining for
      p53 protein. No such staining was evident in tissue taken at first surgery in
      1984. Further analysis of invasive pituitary adenomas may reveal loci associated
      with such behaviour, enabling better prediction of subsequent clinical outcome
      than is possible using standard histological techniques, and delivery of early,
      aggressive treatment to those tumours which show molecular markers associated
      with a poor prognosis.

PMID- 7634511
TI  - Recombinant human insulin-like growth factor-I decreases serum lipoprotein(a)
      concentrations in normal adult men.
AB  - OBJECTIVE: Lipoprotein(a) is a lipoprotein fraction associated with
      atherosclerosis. The serum concentration of lipoprotein(a) has been shown to be
      mainly genetically determined but recently evidence for hormonal regulation has
      been presented. The aim of the present study was to investigate the effects of
      insulin-like growth factor-I on serum lipoproteins, especially lipoprotein(a).
      DESIGN: The effects of one week of IGF-I treatment were studied in an open trial.
      SUBJECTS: Ten healthy men, who participated in a pharmacokinetic study, were
      given recombinant human insulin-like growth factor-I (40 micrograms/kg/day) as
      daily subcutaneous injections. MEASUREMENTS: Serum samples for measurements of
      lipoproteins were taken after an overnight fast before and after 7 days of
      treatment. RESULTS: There was decrease in serum lipoprotein(a) concentration
      (18.5 +/- 5.5%) in nine of the subjects, and a slight increase in one of the
      subjects with the lowest concentrations. Also serum apolipoprotein (b) (6.3 +/-
      2.2%), serum cholesterol (10.6 +/- 1.8%) and serum triglyceride (14.8 +/- 4.8%)
      concentrations decreased. An unexpected finding was that fasting serum glucose
      concentrations increased (13 +/- 4%). CONCLUSION: Insulin-like growth factor-I is
      involved in the regulation of lipoprotein(a) concentrations, which might have
      novel therapeutic implications.

PMID- 7634513
TI  - Fibromatosis of the head and neck.
AB  - Fibromatosis is a locally infiltrative fibrous tissue proliferation with a
      tendency to recur locally. From a large series of head and neck patients treated
      between 1977 and 1994 in our institute, we retrieved the records of nine adult
      patients diagnosed with this disease. They serve as examples to demonstrate this
      rare entity in the head and neck. Five out of nine lesions were localized in
      level V (posterior triangle of the neck). The majority of patients were treated
      by surgery in combination with radiotherapy. None of the patients died of the
      disease.

PMID- 7634514
TI  - Re-innervation of facial nerve territory using a composite hypoglossal nerve-
      muscle autograft--facial nerve bridge. An experimental model in sheep.
AB  - The hypoglossal nerve has been used both entirely and in part to repair the
      facial nerve. Using the partial technique it may be difficult to obtain
      sufficient length and a free interposed graft is then required to extend the
      hypoglossal element. In six sheep the facial nerve was excised between its
      emergence from the stylomastoid foramen and its bifurcation in the parotid gland.
      The hypoglossal nerve was exposed and split longitudinally producing a limb which
      was reflected towards the distal stump of the facial nerve. This left a gap of 4
      5 cm which was bridged with a freeze-thawed coaxially aligned skeletal muscle
      autograft. The sheep were examined at 8 months. Laser doppler blood-flow studies
      showed the blood-flow distal to the graft to be about 25% of that at an
      equivalent site on the normal side. Peak nerve conduction velocities were also
      reduced on the repaired side but stimulation of the proximal hypoglossal nerve
      was nevertheless capable of causing adequate contraction of both facial and
      tongue muscles. Histological comparison of the repaired facial nerves with
      equivalent sites on the normal side showed a reduction in mean axon and fibre
      diameters with normal myelin sheath thickness for the regenerated axon sizes. All
      of these features are to be expected in a regenerated nerve and are consistent
      with a good level of recovery of function.

PMID- 7634516
TI  - Thyroplasty to improve the voice in patients with a unilateral vocal fold
      paralysis.
AB  - Unilateral vocal fold paralysis may cause incomplete closure of the glottis and a
      poor voice. Thyroplasty is a relative new operation to improve the voice by
      'medialization' of the paralysed vocal fold. In our series of 29 patients 24
      (83%) were satisfied and 26 (90%) had a better voice. After the operation the
      voice was louder, clearer and easier to understand. The dynamic and melodic
      ranges on the phonetogram were wider; maximum loudness and maximum phonation time
      were improved. There were no complications during the follow-up of 4 months to 5
      years. In the three patients whose voice was not improved, the vocal fold
      paralysis was due to local trauma and scarring.

PMID- 7634515
TI  - Ototoxicity and nephrotoxicity of gentamicin vs netilmicin in patients with
      serious infections. A randomized clinical trial.
AB  - In the treatment of serious infection by aminoglycoside antibiotics multiple
      daily treatment with netilmicin is considered to be the least toxic. Studies
      comparing netilmicin with gentamicin using the less toxic once-daily schedule are
      lacking. A randomized prospective study was designed to evaluate the efficacy and
      toxicity of once-daily netilmicin with gentamicin treatment in patients with
      serious infections. Consecutive patients with serious infections were randomized
      between gentamicin 4 mg/kg q24h iv or netilmicin 5.5 mg/kg q24h iv. Exclusion
      criteria were neutropenia or severe renal failure. A good clinical response was
      observed in 50 of the 54 evaluable patients (92.6%) treated with gentamicin and
      in 48/52 (92.3%) netilmicin treated patients. Nephrotoxicity developed in 5/72
      (6.9%) gentamicin patients and in 10/69 (14.5%) treated with netilmicin.
      Audiometry was performed with high-frequency audiometry when possible; no
      significant differences were found between the two aminoglycosides. We conclude
      that with once-daily treatment no benefit of netilmicin over gentamicin regarding
      nephro- or ototoxicity could be demonstrated.

PMID- 7634517
TI  - Tonsillar fossa obliteration and post-operative pain.
AB  - Fifty consecutive patients over the age of 15 years undergoing tonsillectomy had
      one tonsillar fossa obliterated by 2/0 Polydioxanone (PDS II) suture. The
      opposite side was used as a control. Pain was assessed on a visual analogue scale
      from the first to tenth post-operative day. Although on the initial post
      operative days the pain was more on the sutured side, 41 patients subsequently
      experienced significant pain relief on that side (P = 0.0001). No complications
      were encountered due to the tonsillar fossa obliteration. On the 10 day review,
      the 41 patients indicated in their questionnaire that tonsillar fossa
      obliteration is a useful procedure to reduce the post-operative pain and would
      have preferred both sides to be obliterated rather than left to heal by secondary
      intention.

PMID- 7634518
TI  - Diabetes mellitus and hearing loss.
AB  - A prospective hearing survey was performed in a sample of 102 diabetic patients.
      The hearing data were compared with the hearing thresholds of three control
      population groups. A significant difference was found in the average hearing
      thresholds between the diabetic patients and all of the three control
      populations. Diabetic patients have worse hearing threshold levels especially at
      low and mid frequencies (P < 0.001). There was also a correlation between the
      duration of diabetes and hearing loss. No significant correlation was found
      between the different stages of diabetic retinopathy and the degree of hearing
      loss.

PMID- 7634520
TI  - Lymphoma presenting to a head and neck clinic.
AB  - Lymphomas generally have a good prognosis compared with squamous carcinomas. The
      present study investigates a series of 185 lymphomas of the head and neck seen
      over a 30-year-period. The records of 236 patients were examined and the
      histology slides reviewed. The lymphomas were classified according to the working
      formulation method and staged using the Ann Arbor system. A total of 185 patients
      had a non-Hodgkin's lymphoma, of those 43 were low grade, nine intermediate and
      103 high grade. The histology slides of 30 patients were not available for
      review. In addition, 51 patients had Hodgkin's disease. One hundred and fifty
      patients were stage 1 or 2 and 74 stage 3 or 4. In 12 patients insufficient data
      was available for staging; 152 were extranodal and 84 nodal. The 5-year survival
      of those patients with Hodgkin's disease was 73%. For the patients with non
      Hodgkin's lymphoma the 5-year survival was 43% for low grade and 48% for high
      grade lesions. The survival of patients with Hodgkin's disease was significantly
      better than for non-Hodgkin's lymphoma (P < 0.01). The 5-year survival of
      patients with extranodal disease was 54% and for patients with nodal disease 65%
      (P = NS). Treatment was by irradiation for localized lesions and by chemotherapy
      or a combination for more advanced lesions. Lymphomas have a relatively good
      prognosis in the head and neck as elsewhere in the body and every effort should
      be made to provide adequate diagnosis and treatment in combined clinics.

PMID- 7634519
TI  - Auditory brain-stem response audiometry in patients with Bell's palsy.
AB  - To evaluate the hypothesis of central nervous system involvement in Bell's palsy,
      the auditory brain-stem responses (ABR) of 32 patients were studied. In 14
      (43.7%) of these patients ABR abnormalities were found. In each case the ABR
      deviation suggested prolonged brain-stem conduction time, independent of the side
      or severity of the paralysis. Site of lesion tests in this sample failed to
      demonstrate eighth nerve dysfunction and, thus, does not support a theory of a
      polyneuropathy that involves the auditory nerve.

PMID- 7634521
TI  - Thyroidectomy during laryngectomy for advanced laryngeal carcinoma--whole organ
      section study with long-term functional evaluation.
AB  - Whole organ step-serial section of laryngectomy specimens was carried out in 16
      patients with a T3 and T4 laryngeal carcinoma to study the involvement of the
      thyroid gland. Three patients (19%) were found to have tumour invasion into the
      thyroid gland, and two patients (16%) were found to have tumour on the thyroid
      capsule. Of the 12 patients who had tumour involving the subglottic region, five
      patients were found to have involvement of the thyroid gland. Of the remaining
      four patients without subglottic tumour extension, none had tumour involvement of
      the thyroid gland. Of the five patients who had long-term survival of 10 years,
      two patients had subclinical hypothyroidism and one patient had clinical
      hypothyroidism. We recommend routine hemithyroidectomy when the subglottic region
      is involved by tumour. The whole thyroid gland should be preserved when the
      laryngeal tumour is confined to the supraglottic and glottic regions without
      clinical evidence of thyroid gland involvement.

PMID- 7634522
TI  - A canalplasty technique for the surgical treatment of chronic otitis externa.
AB  - This article describes a surgical technique for the treatment of chronic
      stenosing otitis externa. A retrospective survey of the post-operative course in
      eight patients (10 ears) showed this to be a satisfactory treatment with no
      recurrence of symptoms.

PMID- 7634523
TI  - The effect of recurrent tonsillitis and tonsillectomy on growth in childhood.
AB  - The aim of this study was to determine if children with recurrent tonsillitis are
      smaller than expected before tonsillectomy and if they have an altered height or
      weight gain 1 year post-operatively. All (204) children attending the hospital
      for tonsillectomy with or without adenoidectomy had their height and weight
      measured pre-operatively and 1 year after operation. The results of 2204 children
      in local schools were used as a control population. Analysis was by comparison of
      each population with the Tanner charts. This study suggests that our population
      of children listed for tonsillectomy were not lighter or smaller than expected
      before operation but that one year after tonsillectomy, there was an increase in
      their weight gain. The height gain was no different than expected after
      operation. Overweight seems to be a medium term complication of tonsillectomy. It
      may be necessary to redefine the indications for tonsillectomy in children who
      are already obese.

PMID- 7634524
TI  - Alport's syndrome: can carriers be identified by audiometry?
AB  - Alport's syndrome is characterized by familial nephropathy with haematuria,
      sensorineural hearing loss and ocular abnormalities. It is transmitted as an X
      linked dominant condition. In the affected males the symptoms are severe compared
      with females who show a more variable clinical picture due to the effect of
      lyonization of the X-chromosome. The diagnosis of carriers of genetic disease is
      extremely valuable for the purpose of counselling the patients as well as their
      relatives. A number of attempts have been made in the past to diagnose these
      carriers. Some studies have shown that it is possible to diagnose carriers of
      conditions where hearing loss is a symptom, by sensitive audiometric techniques.
      In this study we examined obligate and possible carriers of Alport's syndrome
      with pure-tone audiometry (PTA) and the audioscan method. We found that all
      obligate carriers and a predictable proportion of possible carriers had either a
      hearing loss on PTA or a mid frequency notch in the audioscan.

PMID- 7634525
TI  - A prospective study of day case adenoidectomy.
AB  - Adenoidectomy in this country is typically performed as an in-patient procedure
      requiring an overnight stay in hospital but experience from other countries shows
      that adenoidectomy can be safely performed as a day case procedure. In Leicester,
      a prospective study of day case adenoidectomy was initiated in 1991 under
      carefully monitored conditions. We report on 721 patients entered in the first 3
      years. We have so far found day case adenoidectomy to be a safe procedure.

PMID- 7634526
TI  - Partial vertical laryngectomy for recurrent glottic carcinoma.
AB  - Partial vertical laryngectomy for recurrent glottic carcinoma was performed in 61
      patients according to stringent criteria. The great majority of the recurrent
      tumours appeared within 2 years of radiotherapy (80%). The mean follow-up after
      surgery was 79 months. At 5 years 85% of the patients were free of local
      recurrence. Nine patients (15%) developed a local recurrence; eight of them
      underwent total laryngectomy; one patient refused the operation and died. Seven
      patients died of other causes. The actuarial overall survival rate was 88% at 5
      years. Post-operative complications were seen in 12 patients (20%); nine of these
      patients developed airway problems. One patient underwent total laryngectomy for
      severe aspiration, the others finally were decannulated. The results of this
      study indicate that partial vertical hemilaryngectomy for irradiation failures is
      a safe procedure with good results without undue morbidity.

PMID- 7634527
TI  - Human papillomavirus (HPV) is rarely present in normal oral and nasal mucosa.
AB  - The association between human papillomavirus (HPV) and cervical carcinomas is
      well known. HPV has been found in oral carcinomas and paranasal papillomas, and
      the question of a causal role of HPV has yet to be answered. Reports on the
      frequency of HPV in oral and paranasal sinus tumours should be considered in
      relation to the frequency of HPV in normal oral and nasal mucosa. In the present
      study 61 normal individual had oral smears taken and 48 had nasal smears. These
      were examined for HPV by DNA amplification with HPV consensus primers. HPV was
      not found in the oral mucosa, while a single individual harboured HPV in the
      nasal mucosa. It is concluded that HPV is rarely present in normal oral and nasal
      mucosa.

PMID- 7634528
TI  - Idiopathic epistaxis, haemostasis and alcohol.
AB  - Recent studies have suggested a link between antiplatelet medications and alcohol
      in the aetiology of acute adult epistaxis. The possibility that adult epistaxis
      may be associated with alcohol induced platelet dysfunction has not previously
      been investigated. This study evaluated primary haemostasis in 50 adult patients
      with idiopathic epistaxis. A detailed alcohol history was recorded and the
      Simplate bleeding time device was used to test haemostatic function. Forty-six
      per cent of patients were found to have an abnormality of primary haemostasis.
      Prolongation of the bleeding time was significantly associated with a history of
      alcohol use. The effect of alcohol on the bleeding time duration was significant
      (P < 0.001) even at low levels of intake of between 1 and 10 units per week.
      Although prevalent in the study group (42%) the use of non-steroidal anti
      inflammatory drugs did not confer a significant additional risk of increased
      bleeding time. These findings support the importance of alcohol induced
      haemostatic abnormalities in the aetiology of adult epistaxis.

PMID- 7634529
TI  - The effect of temperature on nasal ciliary beat frequency.
AB  - Using a photometric method of measuring ciliary beat frequency, the effect of
      temperature on ciliary activity was investigated. A linear increase in ciliary
      beat frequency between 19 degrees and 32 degrees C was found. Between 32 degrees
      and 40 degrees a plateau was reached in which temperature did not significantly
      affect frequency and above 40 degrees C the frequency began to decline. It is
      concluded that nasal cilia are not critically dependent upon temperature in the
      range 32 degrees and 40 degrees C, the temperature range in which this tissue
      normally operates.

PMID- 7634530
TI  - Is it appropriate to perform adenoidectomy tonsillectomy or adenotonsillectomy on
      a day case basis?

PMID- 7634531
TI  - Nasal airflow sensation.

PMID- 7634532
TI  - Correlation between magnitude of CAG repeat length alterations and length of the
      paternal repeat in paternally inherited Huntington's disease.
AB  - An increasing number of diseases are being found to be due to elongation of
      specific trinucleotide repeat sequences. Inverse correlation between the age at
      onset and the length of the repeat has been found in most of these. The elongated
      CAG repeat causing Huntington's disease is highly unstable when inherited from an
      affected father. In this study we found an average parent-to-offspring difference
      of +0.08 repeat units in maternally inherited repeats, significantly less than
      the average difference of +2.92 repeat units with paternal transmission. Large
      repeat expansions, of more than 5 repeat units, were seen only in paternally
      inherited cases. With paternal transmission the magnitude of repeat length
      alterations was directly correlated to increasing paternal repeat length.
      Increasing variation in repeat length among siblings was correlated to increasing
      average repeat length in the sibship in both maternally and paternally inherited
      HD. Comparison of the magnitude of repeat length alterations to parental age at
      the time of birth of the offspring showed no correlation.

PMID- 7634534
TI  - Autosomal recessive retinitis pigmentosa locus maps on chromosome 1q in a large
      consanguineous family from Pakistan.
AB  - A large Pakistani family with several consanguineous marriages is described, in
      which autosomal recessive retinitis pigmentosa is segregating. Linkage studies
      revealed close linkage between the disease locus and six loci on chromosome 1q
      (D1S158, F13B, D1S422, D1S412, D1S413, and D1S53) with maximum lod scores ranging
      from 0.988-4.657 at theta = 0.065-0.235. However, the analysis of individual
      nuclear families showed very close linkage without recombination in three
      branches and several recombinants and negative lod scores throughout in the
      fourth branch. These results strongly suggest that mutations of two different
      genes are responsible for the disease in the 'linked' and 'unlinked' branches.
      Parallel to the linkage heterogeneity, clear phenotypic differences have been
      observed among the 'linked' and 'unlinked' parts. Our findings demonstrate that
      in case of recessive disorders the possibility of non-allelic genetic
      heterogeneity should always be considered, even within the same kindred and in
      genetic isolates if a largely extended pedigree is analysed.

PMID- 7634533
TI  - Association of HincII RFLP of low density lipoprotein receptor gene with obesity
      in essential hypertensives.
AB  - Obese (BMI > or = 26 kg/m2; n = 51) and lean (BMI < 26 kg/m2; n = 61) Caucasian
      patients with severe, familial essential hypertension, were compared with respect
      to genotype and allele frequencies of a HincII RFLP of the low density
      lipoprotein receptor gene (LDLR). A similar analysis was performed in obese (n =
      28) and lean (n = 68) normotensives. A significant association of the C allele of
      the T-->C variant responsible for this RFLP was seen with obesity (chi 2 = 4.6, P
      = 0.029) in the hypertensive, but not in the normotensive, group (odds ratio =
      3.0 for the CC genotype and 2.7 for CT). Furthermore, BMI tracked with genotypes
      of this allele in the hypertensives (P = 0.046). No significant genotypic
      relationship was apparent for plasma lipids. Significant linkage disequilibrium
      was, moreover, noted between the HincII RFLP and an ApaLI RFLP (chi 2 = 33, P <
      0.0005) that has previously shown even stronger association with obesity (odds
      ratio 19.6 for cases homozygous for the susceptibility allele and 15.2 for
      heterozygotes). The present study therefore adds to our previous evidence
      implicating LDLR as a locus for obesity in patients with essential hypertension.

PMID- 7634535
TI  - Exclusion mapping of the benign hereditary chorea gene from the Huntington's
      disease locus: report of a family.
AB  - A Greek family is presented in which seven members suffered from benign
      hereditary chorea (a rare autosomal dominant non-progressive chorea without
      dementia). All patients and three informative healthy relatives were submitted to
      DNA analysis using probes from loci linked to Huntington's disease. The results
      confirm one previous suggestion that these two disorders are not allelic and that
      they should be considered as two distinct genetic entities.

PMID- 7634536
TI  - A family with unusual Waardenburg syndrome type I (WSI), cleft lip (palate), and
      Hirschsprung disease is not linked to PAX 3.
AB  - An unusual family with Waardenburg syndrome type 1 (WSI), cleft lip (palate), and
      Hirschsprung disease is not linked to the PAX 3 gene since there is an obligate
      crossover which has occurred between PAX 3 DNA markers and the disorder in this
      family. This family may also have anticipation of the WSI traits as the proband's
      grandmother is nonpenetrant, his mother has dystopia canthorum, and severe cleft
      lip (palate), while the proband has dystopia canthorum, severe cleft lip
      (palate), and Hirschsprung disease. Thus, a locus other than PAX 3 is implicated
      in this Waardenburg-like syndrome with Hirschsprung disease and cleft lip
      (palate).

PMID- 7634537
TI  - Quantitation of fibrillin immunofluorescence in fibroblast cultures in the Marfan
      syndrome.
AB  - The Marfan syndrome (MFS) is a heritable connective tissue disorder manifested by
      defects in the skeletal, ocular, and cardiovascular systems. Diagnosis of MFS is
      based on clinical findings. At present there are no laboratory tests for specific
      determination of this disorder. Defects in fibrillin, an elastin-associated
      microfibrillar glycoprotein, are now known to cause the variable and pleiotropic
      manifestations of MFS. Immunofluorescence studies of skin sections and dermal
      fibroblast cultures were the first to show this association. Most unequivocal
      cases of the Marfan syndrome exhibited an apparent reduction in fibrillin
      immunofluorescence. The prospect of examining patients whose clinical findings
      suggest a possible diagnosis of the Marfan syndrome has stimulated us to attempt
      quantitation of immunofluorescence. In the study described here we used computer
      enhanced image analysis to establish "normal" and "abnormal" (Marfan) parameters
      of fibrillin immunofluorescence in dermal fibroblast cultures. Quantitation of
      fluorescence from control individuals showed a median of 21%, while the median
      fibrillin fluorescence in MFS patients was 6% with a confidence interval of < or
      = 15%. These findings were statistically significant to p < 0.01. It is hoped
      that these analyses may become a useful adjunct in the clinical diagnosis of MFS.

PMID- 7634538
TI  - Event-related potentials (ERPs) and intelligence in neonatally identified 47,XXY
      males.
AB  - The event-related potentials (ERPs) of 18 extra X males (mean age 18.1 years)
      were recorded during the course of phonemic and orthographic discrimination
      tasks. The N2 and P3 latencies and amplitudes of subjects were examined in
      relation to their verbal and nonverbal intelligence test scores based on
      assessments at three ages: prior to puberty, during puberty and at sexual
      maturity. The results indicated that verbal abilities at most test occasions were
      significantly related to P3 latencies. Nonverbal abilities were largely
      uncorrelated with ERPs. The findings suggest that the verbal deficits of extra X
      males are the result of unlateralized individual differences in neural cognitive
      processing.

PMID- 7634539
TI  - Confidentiality in counseling for X-linked conditions.
AB  - Genetic counseling in a synthetic fragile-X family is used to illustrate some
      dilemmas which may arise from the genetic counselor's wish to respect the
      patient's confidence. What is the counselor's obligation towards family members
      who are unaware that they are carriers? Should the counselor try to avoid
      disclosing information concerning such family members to the patient, and if so
      how? May the future father of an affected fetus be prevented from participating
      in the reproductive decisions concerning that fetus, out of respect for the
      mother's wishes?

PMID- 7634540
TI  - Cytogenetic analysis of 23 Japanese patients with amyotrophic lateral sclerosis.
AB  - The cytogenetic analysis of 23 Japanese patients with amyotrophic lateral
      sclerosis is reported. G-banded chromosomes of cultured peripheral blood
      lymphocytes of one subject had a constitutional chromosomal translocation,
      t(7;13)(p22;q21). No constitutional chromosome abnormality was found in any of
      the other 22 Japanese patients with amyotrophic lateral sclerosis tested.

PMID- 7634542
TI  - Familial benign setting-sun phenomenon in healthy newborns.

PMID- 7634541
TI  - Clinical and molecular genetic findings in five patients with Miller-Dieker
      syndrome.
AB  - Five patients with type 1 lissencephaly, typical features of Miller-Dieker
      syndrome and apparently normal karyotypes were investigated for microdeletions in
      chromosome 17p13.3. Analysis of loci D17S5 and D17S379 by polymerase chain
      reaction and fluorescence in situ hybridization revealed a deletion in three
      cases. No deletion was observed in the remaining two cases. Given the almost
      identical clinical picture of the five patients, the great variation in the
      molecular findings argues against Miller-Dieker syndrome being a contiguous gene
      syndrome.

PMID- 7634543
TI  - Renal disease and patient survival in light chain deposition disease.
AB  - We evaluated retrospectively the presenting clinical features, response to
      treatment and clinical course of 19 patients with LCDD, 11 of whom had multiple
      myeloma. At presentation, renal insufficiency was present in 18 patients and
      proteinuria in 16. Renal biopsy revealed typical LCDD in 16 patients, while in
      the remaining three LCDD was associated with other abnormal tissue deposits.
      Extrarenal signs were observed in 12 patients (63%), with the liver, heart and
      peripheral nerves being the most frequently involved organs. After diagnosis, 18
      patients underwent therapy: 2 received steroids alone and 16 were treated with
      steroids and cytotoxic drugs; 7 patients also underwent plasma exchange. At the
      end of the first month of treatment renal function improved in 5 patients,
      worsened in 5 and remained unchanged in 8. All but 3 of the patients continued
      treatment beyond the first month: 7 patients developed end-stage renal disease, 5
      an improvement and 4 a worsening in renal function. No effect on proteinuria was
      observed. Extrarenal symptoms developed in 4 previously unaffected patients and
      in 3 others they extended to more organs. Sixteen patients died: 12 during the
      first year of the follow-up, and 4 at 21st, 34th, 37th and 82nd month of
      observation. Five patients died from neoplastic cachexia, 4 from hypokinetic
      cardiopathy, 3 from hemorrhagic complications, 2 from pneumonia and one from
      unknown cause. Mean patient survival after presentation was 18.1 +/- 20.7
      months.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7634544
TI  - Evaluation of complications due to percutaneous renal biopsy in allografts and
      native kidneys with color-coded Doppler sonography.
AB  - We studied 142 consecutive percutaneous renal biopsies (puncturing on 73
      allografts and 69 native kidneys) which were performed under continuous
      ultrasonic guidance, on 133 adult patients. The patients were monitored, at
      least, during the next 24 hours. We compared the complication rate for biopsies
      recording clinical and biochemical data and, the day after the biopsy, the kidney
      was examined with a color-coded Doppler sonography (CCDS): in real-time survey of
      the kidney and with spectral wave form analysis. The diagnosis of arteriovenous
      (AV) fistula was achieved detecting increased color saturation toward white, high
      peak systolic flow velocity and low resistive index in the supplying artery.
      Three procedures were excluded of the analyses because of incomplete data
      recorded, although none of them showed any remarkable complication. There was a
      94.3% rate of successful biopsies. The mean +/- SEM number of glomeruli under
      light microscopic examination was 8.5 +/- 0.6. Complications occurred 64 times in
      relation to 55 patients with a higher incidence in allografts (61%) than in
      native kidneys (31%). Renal transplant patients showed higher serum creatinine
      values (5.8 +/- 0.8 vs. 3.2 +/- 0.4; p > 0.0001) and lower hematocrit (31.3 +/-
      1.1 vs. 34.4 +/- 0.9; p = 0.025) than the native-kidney patients at the time of
      biopsy. De novo hematuria occurred in 30% of the procedures. In transplant
      patients, the gross hematuria incidence (9.9%) more than doubled that showed by
      native-kidney patients. The incidence of serious complications (hematoma,
      hemoperitoneum and AV fistula) was 16.5% and these were more frequent in
      transplant than in native kidneys.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7634545
TI  - Percutaneous renal biopsy of ventilated intensive care unit patients.
AB  - The etiology of acute renal failure in ventilated intensive care unit patients
      can be determined non-invasively in more than 80% of cases. When a pulmonary
      renal syndrome is suspected however it is important to obtain histological
      confirmation of the diagnosis prior to initiating therapy. Most text books and
      review articles have advocated the use of open surgical biopsy in this situation.
      Seven years ago we began to perform percutaneous renal biopsies on medical
      intensive care unit ventilated patients when a pulmonary renal syndrome was
      suspected as an alternative to an open surgical procedure. During this period we
      performed the technique on 7 patients. Adequate renal tissue was obtained in all
      cases. We compare the complication rate with that achieved using open surgical
      biopsy during the same time period. The complication rate using a percutaneous
      technique was similar to open renal biopsy. We believe that the previously held
      recommendation that percutaneous renal biopsy should not be performed on
      ventilated patients should be re-examined.

PMID- 7634546
TI  - Effects of posture on creatinine clearance and urinary protein excretion in
      patients with various renal diseases.
AB  - To investigate the effects of a change in posture on renal function, we measured
      Ccr and the urinary excretion of protein, albumin, immunoglobulin G (IgG) and
      transferrin in 80 patients with renal disease and in 9 healthy controls. Patients
      and controls were studied serially while supine for 60 min; then after standing
      upright for 60 min. Almost all subjects showed a drop in the Ccr with standing (p
      < 0.01). The percent change in Ccr after standing was more remarkable in patients
      with glomerulonephritis vs the healthy subjects (74.0 +/- 21.9% vs 89.9 +/-
      12.3%, p < 0.01). The change in urinary excretion of protein and albumin after
      standing in patients with membranous nephropathy (MN-N) significantly exceeded
      that in patients with IgA nephropathy (IgA-N) (182.1 +/- 89.3% vs 108.1 +/- 59.2%
      in urinary protein and 181.7 +/- 98.7% vs 113.3 +/- 40.9% in urinary albumin, p <
      0.01). Urinary excretion of IgG and transferrin tended to increase after standing
      in those two groups, but not significantly. Results indicate that posture affects
      urinary protein excretion, probably via an increase of glomerulocapillary
      hydrostatic pressure and/or change in the permeability of the glomerular
      capillary walls. We recommend that comparable postures should be used when
      protein excretion is used as a diagnostic tool and in monitoring structural
      damage to glomeruli, particularly in patients with membranous nephropathy.

PMID- 7634547
TI  - Renal hemodynamic effects of chronic ketorolac tromethamine treatment in aged
      lean and obese Zucker rats.
AB  - Ketorolac tromethamine is a relatively new non-steroidal anti-inflammatory drug
      (NSAID), with potent analgesic activity. Similar to other NSAIDs, ketorolac has
      the potential to impair renal function. To assess the renal hemodynamic impact of
      the ketorolac in aged lean and obese rats, ketorolac was orally administered to
      46-week-old lean and obese Zucker rats for two weeks. Ketorolac was mixed with
      rat chow in a manner to provide a dose equivalent to 15 mg/kg body weight/day.
      Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were
      measured under anesthesia by standard inulin and p-aminohippuric acid clearance
      method, respectively. Urinary prostaglandin (PG) E2 excretion was measured before
      and after ketorolac treatment. Ketorolac treatment significantly reduced obese
      rat GFR (0.47 +/- 0.08 vs 0.78 +/- 0.03 ml/min/g, p < 0.002) and ERPF (1.12 +/-
      0.14 vs 2.36 +/- 0.26 ml/min/g, p < 0.001) relative to obese control rats. In
      comparison, ketorolac did not significantly alter lean rats GFR (0.77 +/- 0.04 vs
      0.91 +/- 0.06 ml/min/g) or ERPF (1.92 +/- 0.20 vs 2.48 +/- 0.15 ml/min/g)
      relative to lean control rats. Chronic ketorolac treatment significantly reduced
      hematocrit by 20 and 30 percent in lean and obese rats relative to controls,
      respectively. The renal vascular resistance was significantly increased with
      ketorolac treatment in obese rats (36 +/- 4 vs 79 +/- 14 mmHg/ml/min, p < 0.001)
      but not lean rats (28 +/- 3 vs 38 +/- 5 mmHg/ml/min, NS) relative to
      corresponding controls.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7634548
TI  - Long-term high dose intravenous calcitriol therapy in end-stage renal disease
      patients with severe secondary hyperparathyroidism.
AB  - We prospectively studied the long-term effects of intravenous calcitriol in 17
      hemodialysis patients with severe secondary hyperparathyroidism (HPT) for 25.7 +/
      3.4 (+/- SE) months. Calcitriol was given thrice weekly after dialysis.
      Subsequently, changes were made every 3-4 weeks based upon serum chemistries.
      Total calcium and inorganic phosphorus were measured weekly; alkaline phosphatase
      (AP) and IRMA-PTH were measured monthly. Inorganic phosphate was controlled with
      calcium supplements. With calcitriol therapy both IRMA-PTH and AP decreased from
      876 +/- 113 to 65 +/- 13 pg/ml (p < or = 0.001) and 432 +/- 106 to 103 +/- 15
      U/ml (p < or = 0.001), respectively. Each patient had a reduction in IRMA-PTH and
      AP. Nadir IRMA-PTH occurred at 55.4 +/- 7.3 weeks. The maximum and mean maximum
      doses of calcitriol were 8.0 and 4.1 +/- 0.4 micrograms thrice weekly,
      respectively. Hypercalcemia tended to occur in those patients who were
      hypercalcemic prior to the initiation of intravenous calcitriol therapy. All
      hypercalcemic episodes were asymptomatic and reversed either by temporary
      withdrawal or lowering of the calcitriol dose. Hyperphosphatemia developed in
      those patients with a history of elevated serum phosphates and was mostly related
      to dietary and medication noncompliance. We conclude that intravenous calcitriol
      was uniformly effective and safe for the long-term therapy of severe HPT in ESRD.
      Careful attention to serum phosphate control is required.

PMID- 7634549
TI  - Calcium in patients on hemodialysis.
AB  - Analyzing 415 measurements from 33 patients on chronic maintenance hemodialysis
      we confirm that 50% of total calcium in the range 1.59 to 3.33 mmol/l gives a
      valuable approximation to ionized calcium in the range 0.79 to 1.62 mmol/l.
      However, a small but significant effect of albumin and phosphate on ionized
      calcium can also be demonstrated. Conventional albumin correction of total
      calcium using the formula: total calcium + (43 g/l-Albumin g/l).0.017 mmol/g is
      of poor value in these patients on maintenance hemodialysis.

PMID- 7634550
TI  - Hyperviscosity syndrome: efficacy and comparison of plasma exchange by plasma
      separation and cascade filtration in patients with immunocytoma of Waldenstrom's
      type.
AB  - The hyperviscosity syndrome is a common problem in patients suffering from IgM
      paraproteinemia. In this situation cytotoxic chemotherapy alone is insufficient
      and additional plasma therapy is required. Until recently, conventional plasma
      exchange was the only plasma therapy available. While this method has proven its
      efficacy, it eliminates proteins unselectively. Cascade filtration, on the other
      hand, has been established to remove proteins as a function of their size
      offering the prospect of a highly selective withdrawal of macromolecules. In the
      work presented, the efficacy of conventional plasma exchange and cascade
      filtration was evaluated performing both techniques at random in cases of
      hyperviscosity syndrome due to immunocytoma of Waldenstrom's type (n = 11/group).
      In these patients, conventional plasma exchange decreased plasma viscosity by
      48%; cascade filtration was less effective (26%), correlating with a smaller
      decrease of IgM (conventional plasma exchange 42% vs cascade filtration 27%). The
      profile of other plasma proteins studied did not change significantly with either
      treatment. Furthermore, we observed no differences regarding serious side
      effects. In conclusion, we could not demonstrate a superior effect of cascade
      filtration as compared to conventional plasma exchange in the treatment of
      hyperviscosity syndrome.

PMID- 7634551
TI  - Pulmonary hemosiderosis and immune complex glomerulonephritis.
AB  - Two children with a syndrome of pulmonary hemorrhage and immune complex nephritis
      are reported. Clinical history suggests that pulmonary lesions precede renal
      abnormalities. Necrotizing glomerulonephritis with granular immune deposits along
      the glomerular basement membrane was found. Although the etiology of this disease
      complex is still unknown, the clinical and pathological findings in these
      patients suggest that immune complex glomerulonephritis is an unusual
      complication of idiopathic pulmonary hemosiderosis.

PMID- 7634552
TI  - Renal involvement in POEMS syndrome.
AB  - We describe a patient with POEMS syndrome (polyneuropathy, organomegaly,
      endocrinopathy, monoclonal gammopathy and skin changes) who was found to have
      renal involvement with particular renal pathological findings. So far, 17 other
      cases, most of them from Japan, of POEMS syndrome with renal involvement, have
      been published. Clinical features are variable: acute renal failure with anasarca
      or moderate chronic renal insufficiency with mild proteinuria. This latter
      presentation often passes unnoticed. There is no severe hypertension, no
      microangiopathic hemolytic anemia. Renal biopsy shows prominent glomerular
      changes which are unusual and distinct from membranoproliferative
      glomerulonephritis (MPGN) and from glomerular thrombotic microangiopathy (TMA).
      Mesangial proliferation and thickening of the capillary wall with double contour
      on light microscopy suggest an MPGN. By immunofluorescent microscopy, no
      immunoglobulins or complement deposits were found. The occurrence of
      mesangiolytic lesions has led to the term of "mesangiolytic glomerulonephritis".
      The presence, on electron microscopy, of lucent subendothelial spaces could
      indicate TMA. But there are neither thrombi nor arteriolar changes. We are
      inclined to consider that the microangiopathic lesions are due to chronic injury
      of glomerular endothelial cells, exacerbated at outbreaks of the disease.
      Increased production of IL 6 could support the efficacy of corticosteroid
      therapy, particularly in acute clinical situations.

PMID- 7634553
TI  - Spontaneous remission of paracetamol induced acute renal failure.

PMID- 7634554
TI  - Empiric therapy of bacteremia with teicoplanin in hemodialysis patients.

PMID- 7634555
TI  - Schoenlein-Henoch purpura with necrotizing vasculitis after cocaine snorting.

PMID- 7634556
TI  - Nephrotic syndrome after recombinant hepatitis B vaccine.

PMID- 7634557
TI  - Granulomatous interstitial nephritis secondary to allopurinol treatment.

PMID- 7634558
TI  - Maintaining long-term control of blood pressure: the role of improved compliance.
AB  - Mild-to-moderate essential hypertension is a major risk factor for stroke and
      cardiovascular mortality and morbidity. Morbidity can be reduced significantly by
      lowering high blood pressure, and with the effective antihypertensive drugs now
      available, it is ever more important to identify and treat the estimated 50 to 60
      million hypertensive persons in the United States. Yet a high percentage of
      persons being treated stop taking their medication and refuse to comply with
      their therapeutic regimen. Many problems relate to maintaining long-term therapy
      in the hypertensive population. They include the cost of medication, a lack of
      written instructions, unclear instructions, noninvolvement of the patient in
      designing the treatment plan, lack of patient education about the disease, side
      effects, and inconvenient dosing schedules. Numerous studies have found that
      compliance increases as drug-dosage frequency decreases, as with the use of once
      daily or sustained-release drug preparations. Other contributors to compliance
      include prescription-refill reminders, appointment reminders, simple written
      instructions about drug use, and patient education about the need for treatment
      and the consequences of noncompliance. Many classes of antihypertensive drugs are
      available, and more are in development. With such an extensive armamentarium
      available, all patients, regardless of coexisting medical conditions, should be
      able to be given effective, individualized antihypertensive therapy.

PMID- 7634559
TI  - Physiologic effects of long-term hypertension control.
AB  - Various antihypertensive agents may reduce blood pressure to a similar degree,
      yet they produce different outcomes with respect to long-term end-organ damage.
      Effective antihypertensive therapy can prevent or even reverse established left
      ventricular hypertrophy. The most rapid and extensive regression occurs with
      agents that block the reninangiotensin system or reduce entry of calcium into the
      cells. Other classes of drugs that reliably reverse left ventricular hypertrophy
      are centrally acting adrenergic inhibitors and beta blockers. The effect of
      antihypertensive agents on atherosclerosis appears to differ widely with regard
      to lipid metabolism, insulin sensitivity, and the biology of endothelium and
      vascular smooth muscle. Hypertension and chronic renal failure (diabetic and
      nondiabetic) are closely allied, but available antihypertensive agents are not
      equally potent in reducing intraglomerular pressure.

PMID- 7634560
TI  - Antihypertensive therapy targeted to the needs of the patient: focus on the renin
      angiotensin system; older and newer agents.
AB  - Antihypertensive drug therapy can lower blood pressure and prolong life, but many
      hypertensive patients continue to develop further risk factors and to die
      prematurely of heart disease. Antihypertensive drugs can also interfere with the
      patient's quality of life, and many are not compatible with the concomitant
      medical conditions of the patient and the medications taken to treat them. For
      these reasons, the antihypertensive therapy selected should meet the specific and
      complete needs of each patient, not just treat the high blood pressure. An
      analysis of the drugs that inhibit the renin-angiotensin system suggests that
      several of these drugs have a more favorable therapeutic profile than other
      classes of hypotensive agents. The newly developed receptor-site-specific
      blockers are expected to be tolerated better by hypertensive patients and,
      consequently, to enhance their quality of life. The first of the new class of
      nonpeptide blockers of the AT1 receptor, losartan--which has no partial agonist
      activity--is likely to have the advantages of the angiotensin-converting enzyme
      inhibitors without their adverse effects, notably cough. In selected patients,
      the AT1-receptor blockers could become the drugs of first choice for the
      management of hypertension.

PMID- 7634561
TI  - Angiotensin receptors: physiology and pharmacology.
AB  - The renin-angiotensin system is critical for regulating extracellular fluid
      volume and blood pressure. Angiotensin II, the active peptide hormone produced by
      the renin enzymatic cascade, sustains vascular volume and blood pressure by
      constricting vessels, stimulating adrenal aldosterone secretion, increasing renal
      tubular sodium absorption, activating the sympathetic nervous system, and
      increasing cardiac contractility. These actions are a disability in the
      pathophysiologic states of hypertension and congestive heart failure (CHF),
      however, since reactive increases in renal renin and angiotensin II stimulate
      sympathetic activity and renal sodium retention, leading consequently to
      circulatory volume over-load. The actions of angiotensin II are mediated by its
      interactions with specific cell-surface angiotensin II receptors, namely, AT1 and
      AT2; most cardiovascular actions of angiotensin II come from its interaction with
      the AT1 receptor. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin
      II-receptor blockers antagonize the actions of the renin-angiotensin axis,
      neutralizing its effects on hypertension and heart failure. Losartan is the first
      oral, nonpeptide, selective AT1-receptor blocker to be approved. Clinical trials
      show it to be effective and well tolerated as therapy for hypertension and CHF.
      Data obtained thus far suggest ACE inhibitors and AT1-receptor blockers have
      similar efficacy for treating these conditions, but the receptor blockers appear
      to produce fewer adverse effects. Whether the sustained increase in angiotensin
      II concentrations after AT1-receptor antagonism produces deleterious effects is
      not known. The concern is that these high levels may stimulate unblocked AT2
      receptor; the effect of that stimulation may not be important, however.

PMID- 7634562
TI  - Evolving concepts in the management of hypertension.
AB  - Currently, a plethora of antihypertensive medications exists. One concern about
      the long-term use of many of these agents is that adverse effects may offset
      their benefits. Despite the availability of many newer agents, blood pressure
      continues to be inadequately controlled in the majority of treated hypertensive
      patients, and many still remain at higher risk of premature death than the
      general population. More than 60% of treated hypertensive patients fail to attain
      blood pressures of < 140/90 mmHg. The major factors that permit a rational choice
      of medication include demographic considerations such as race and age, coexisting
      disease, safety, patient acceptance (quality of life), potential drug
      interactions, and additional salutary effects. The role of nondiuretic
      monotherapy is an integral component of this discussion. Preliminary data
      indicate that the use of calcium-channel blockers, converting-enzyme inhibitors,
      and AII-receptor antagonists constitutes excellent therapy in many patients. The
      effects of medication on the metabolic and lipid profiles are also considered.

PMID- 7634563
TI  - Economic considerations in total hip arthroplasty and implant standardization.
AB  - During the 1980s, the hospital cost for total hip arthroplasty was controlled,
      but the implant cost for total hip arthroplasty was not controlled. With the
      introduction and acceptance of case price payment systems, hip implant cost
      consumed a greater portion of the hospital payment each year during the 1980s.
      Cost control for total hip arthroplasty during the 1990s will require control of
      implant costs. One objective method for controlling implant costs in total hip
      arthroplasty is implant standardization.

PMID- 7634564
TI  - Generic total hip arthroplasty.
AB  - To decrease implant costs for total hip arthroplasty, a number of different
      options are available, including the use of remaindered implants, older designs,
      discounted stock, or specifically designed implants manufactured and sold at low
      cost. To determine the prevalence of these practices, 80 questionnaires were
      mailed to members of the Hip Society; 55 (79%) were completed and returned. In
      addition, 32 questionnaires were mailed to a representative group of orthopaedic
      surgeons in Canada; 29 (90%) were completed and returned. Analysis of these
      returns revealed that 73% of the respondents used a low-cost prosthesis for
      certain indications in total hip arthroplasty. No uniform policy with regard to
      cost containment or to the definition of low cost was apparent. In a parallel
      study, the results of a clinical trial with a generic hip implant in 150 patients
      observed for 2 years or longer revealed the general improvement in hip scores and
      the rate of complication to be compatible with those of other, more-expensive hip
      prostheses. Control of prosthetic costs as a means of influencing the cost of
      arthroplasty appears to be a wide-spread practice.

PMID- 7634565
TI  - Cost awareness and cost containment at the Hospital for Special Surgery.
      Strategies and total hip replacement cost centers.
AB  - To help balance the operating budget of The Hospital for Special Surgery, which
      was encountering an annual major deficit of $4 million in 1989, a program of cost
      awareness leading to cost containment was instituted in 1990. Costs of supplies,
      implants, and equipment were identified and reviewed by the hospital staff,
      including orthopaedic surgeons, orthopaedic residents, health care personnel, and
      administration, for cost effectiveness. Methods to accomplish the goals included
      structuring committees for information; workshops organized by different services
      to affect change; feedback to health care professionals through posters and
      newsletters; and statistical identification for continued education. Major cost
      savings resulted from recycling wasted implants, reduction of costly implants,
      and reduction of unnecessary supplies. As a result, vendors had been challenged,
      leading to more competitive prices. This program has opened new avenues of cost
      reduction without sacrificing quality of medical care and has contributed to a
      breakdown of barriers between medical staff, administration, and finance, leading
      to a strong hospital-team commitment. The price of health care in the United
      States in 1993 exceeded $900 billion. Health care expenditures now account for
      approximately 14% of the gross domestic product. Health care costs have been
      rising faster than the inflation rate for more than a decade. The result is the
      current national focus on containment of health care expenditures.

PMID- 7634566
TI  - Painful olecranon physeal nonunion in an adult weight lifter. A case report.
AB  - Only 3 cases of persistent olecranon physes in adults have been reported
      previously in literature. In each case, physeal nonunion was present bilaterally
      and either unilateral, bipartite, or tripartite patellae were present. A case of
      painful unilateral physeal nonunion in an adult weight lifter is presented. The
      patient had begun competitive weight lifting when he was 14 years old.
      Radiographs of the contralateral olecranon and patellae were normal. After
      failure of conservative treatment, surgical union was achieved, using tension
      band wiring augmented with autologous iliac crest bone graft. The author proposes
      that unilateral olecranon physeal nonunion has a mechanical etiology as opposed
      to a genetic etiology in individuals with bilateral physeal persistence. Surgical
      treatment in the former group is best delayed until after age 19, to allow
      adequate time for spontaneous union.

PMID- 7634567
TI  - Epidemiology of hip fractures among the elderly. Risk factors for fracture type.
AB  - A study was undertaken in September 1988 of 169 patients who were > 50 years of
      age receiving care for hip fractures at 4 university-affiliated hospitals during
      a 2-year period. Demographics, medical history, cognitive function, mobility, and
      environmental factors surrounding the hip fractures were ascertained by patient
      or proxy interview and review of medical records. These were then related to the
      type and severity of hip fracture. Eighty-three (49%) patients had
      intertrochanteric fractures, 23 (14%) had subtrochanteric fractures, and 63 (37%)
      had intracapsular fractures. Walking versus standing, sitting, or getting up at
      the time of fracture (relative odds = 3.2, p = .041), and no mobility difficulty
      versus some mobility difficulty (relative odds = 5.2, p = .047) were associated
      with increased comminution in intertrochanteric or subtrochanteric fractures. The
      location of the fracture occurrence (indoor versus outdoors) was associated with
      greater displacement in intracapsular fractures (relative odds = 6.7, p = 0.021).
      Only 2 of 169 patients had spontaneous hip fractures, defined as hip pain that
      preceded the fall. Because spontaneous fractures are rare, efforts directed
      toward preventing falls would be expected to decrease the incidence of hip
      fractures. Future possibilities include the development of protective garments
      that can reduce impact loading to the hip during a fall.

PMID- 7634568
TI  - Revision and primary hip and knee arthroplasty. A cost analysis.
AB  - The cost of health care in the United States has been rising steadily during the
      past 10 years. Total joint arthroplasty, a commonly performed orthopaedic
      procedure, accounts for approximately $10 billion dollars per year. The objective
      of this study was to perform a clinician-oriented cost analysis of primary and
      revision hip and knee arthroplasty. Twenty-five consecutive cases each of total
      knee arthroplasty, total hip arthroplasty, revision total knee arthroplasty, and
      revision total hip arthroplasty were analyzed. The length of stay and number of
      minutes spent in the operating room were significantly higher for the patients
      with revision hip surgery than for the other groups. The total charges for the
      prosthesis in the 4 groups exceeded 40% of the total charges for the procedure.
      Primary hip and knee surgery had similar billed costs, and work for revision hip
      surgery has a significantly higher billed cost than physician's work. The implant
      selection process by an orthopaedic surgeon performing arthroplasty of the hip
      and knee needs to include economic aspects.

PMID- 7634569
TI  - Anterior cruciate ligament reconstruction. A comparison of 2 techniques.
AB  - This work compares the results of 2 different techniques of anterior cruciate
      reconstruction performed by 2 surgeons with the same rehabilitation program and
      same criteria of results evaluation. Forty-five patients were operated on using
      semitendinous tendon autograft, (average followup, 8 years 4 months), and 30
      patients using bone patellar tendon bone autograft (average followup, 7 years 5
      months). Functional results were evaluated using the Lysholm and Tegner rating
      systems, and clinical laxity or stability were evaluated using the Lachmann and
      Jerk tests. Articular stability and function were significantly better in the
      patients operated on using bone patellar tendon bone autograft.

PMID- 7634570
TI  - Computed tomography analysis of proximal tibial coverage.
AB  - Researchers of this study used computed tomographic studies of the proximal tibia
      for patients undergoing total knee arthroplasty to determine basic morphologic
      data of size, shape, and area of varying levels from the articular surface. Five
      off-the-shelf tibial component shapes (4 symmetric, 1 asymmetric) were templated
      to determine the fit of the components at the various resection levels. Seventy
      two knees were assessed at 2-mm, 68 at 5-mm, 40 at 8-mm, and 17 at 11-mm
      resection levels. Significant differences in fit and percentage of total area of
      coverage were identified. Fit was significantly better for asymmetric as compared
      with the symmetric components (p = 0.001) at all levels of resection. Fit was
      significantly worse for each component as the resection depth increased. This
      information can serve as a bridge to clinical and laboratory data in identifying
      the importance of tibial component fit to the overall performance of a total knee
      arthroplasty design.

PMID- 7634571
TI  - The treatment of aneurysmal bone cyst.
AB  - Forty-four patients with aneurysmal bone cysts were treated with curettage with
      or without bone grafting, and in 26 (59%) recurrence developed. Of 11 patients
      treated with radiation, in only 1 (9%) the disease was not controlled. In 1
      patient, radiation-induced sarcoma developed. Since the introduction of
      cryosurgery 27 years ago, 51 patients have been treated with cryosurgery. The
      patients had an average age of 13 years (range, 2-32 years). Thirty-four primary
      aneurysmal bone cysts and 17 secondary aneurysmal bone cysts occurred in
      association with 7 giant-cell tumors, 5 chondroblastomas, 2 fibromyxomas, 2
      nonossifying fibromas, and 1 unicameral bone cyst. The tumors were classified as
      inactive in 9 patients, active in 31, and aggressive in 11. Treatment consisted
      of local intralesional excision followed by application of liquid nitrogen. The
      defect was either allowed to heal spontaneously (n = 26) or was reconstructed
      using an intramedullary rod (n = 2), bone grafts (n = 5), fibular strut grafts (n
      = 14), or polymethylmethacrylate with Steinmann pins (n = 4). At median followup
      of 85 months (range, 24-311 months), the overall cure rate was 82%. This was
      increased to 96% after a second, or repeat, cryosurgery. The disease in all
      patients eventually was controlled by cryosurgery. The mean functional rating was
      90% (range, 63%-100%). Intralesional excision with adjunctive cryosurgery is an
      effective method for the treatment of aneurysmal bone cyst.

PMID- 7634573
TI  - Effect of anterior cruciate ligament reconstruction with patellar tendon or
      prosthetic ligament on the morphology of the other ligaments of the knee joint.
      An experimental study in dogs.
AB  - The effect of anterior cruciate ligament replacement on the other ligaments of
      the knee, including the medial or lateral collateral and posterior cruciate
      ligaments, was studied histologically in the canine knee. The anterior cruciate
      ligament was replaced either with the medial third of the patellar tendon or with
      a prosthetic ligament. Histologic analysis was performed 3 months after
      prosthetic ligament implantation and 1 year after patellar ligament
      reconstruction. In all ligaments, numerous pathologic alterations were found.
      Degenerative changes such as glycosaminoglycan accumulation, metachromasia,
      collagenolysis, collagen necrosis, and lipomatosis were similar after 3 months
      and after 1 year. Granulation tissue, a sign that characterizes tissue repair,
      was seen only in those ligaments taken 3 months after anterior cruciate ligament
      surgery. Similar degenerative changes also were found in the ligaments of the
      knees with only a large medial arthrotomy (sham). In the contralateral control
      knees, the pathologic alterations were rare. Thus, open arthrotomy alone or with
      anterior cruciate ligament reconstruction seems to result in longstanding
      degenerative changes in all ligaments of the canine knee joint.

PMID- 7634572
TI  - Proximal humeral reconstruction after excision of a primary sarcoma.
AB  - From 1978 to 1991, 19 patients underwent wide resection of the proximal humerus
      for a primary bone tumor. Reconstructions included intercalary autoclaved
      autograft and Neer prosthesis composites in 11 patients, intercalary allograft
      and Neer prosthesis composites in 4 patients, and a Neer prosthesis with
      methylmethacrylate in 4 patients. All patients were observed for at least 2 years
      or until death. The functional results and complications of the 19 procedures
      were evaluated. Function was rated as excellent for 17 patients and good for 2
      patients. There were no failures of fixation. Local recurrence occurred in 2
      patients. There were 2 cases of recurrent anterior subluxation and 1 of
      dislocation. Two superficial wound infections were treated successfully with
      local debridement and antibiotics. The authors conclude that autoclaved autograft
      or allograft when combined with a long-stem cemented Neer prosthesis offers an
      excellent composite for proximal humeral reconstruction.

PMID- 7634574
TI  - The intramedullary hydraulic pressure tolerance of the human femur.
AB  - A new range of clinically used, biodegradable, bone-bonding copolymers has
      hydrogel properties. With intramedullary press fit, these polymers generate
      considerable pressure through swelling caused by water absorption. In total hip
      arthroplasty, high intramedullary pressures can be attained by insertion of the
      prosthesis into femora by using methylmethacrylate cement and a cement plug.
      Because the effects of such intramedullary pressures are not fully known, 10-cm
      long segments of the proximal diaphysis of fresh femoral bones from 22 human
      cadavers were tested for their intramedullary pressure resistance. The
      intramedullary pressure resistance, calculated burst forces, and stress on the
      bone were correlated to age, gender, bone mineral content per unit length, and
      bone mineral density. In most bone segments, a burst fracture occurred just
      opposite the linea aspera. The hydraulic bursting pressures ranged from 2.3 to
      13.4 MPa (age adjusted gender effect [male-female], 2.2 MPa [p = 0.05]). The
      forces at fracture were calculated to be between 265 and 1361 N (regression
      coefficient: 247/unit bone mineral content per unit length). The tangential
      stress appeared to be between 7.54 and 27.54 MPa (regression coefficient:
      11.6/unit bone mineral density; bone mineral density adjusted gender difference
      [male-female], 4.5 MPa [p < 0.05]). Biochemical examination of the bones did not
      show any abnormalities. The results of this study show that the human femora can
      resist mechanically an intramedullary pressure of at least 2 MPa. From a
      mechanical point of view, intramedullary pressures generated by swelling polymers
      should remain below 2 MPa for safe use.

PMID- 7634575
TI  - Effect of disc lesion on microdamage accumulation in lumbar vertebrae under
      cyclic compression loading.
AB  - A relationship between disc lesion and microdamage accumulation in adjacent
      vertebrae during fatigue loading was investigated in a canine model. Eighteen
      functional spinal units obtained from 6 skeletally mature mongrel dogs were
      divided into 3 groups: I, control (without loading) (n = 6); II, loading with
      normal disc (n = 6); and III, loading with disc lesion created by nucleotomy (n =
      6). Physiologic cyclic compression was performed for 10(5) cycles, and fractional
      trabecular bone area and microcrack density in the vertebrae were measured. There
      was a significant difference in microcrack density among groups and regions (p <
      0.0001) with significantly more microdamage in functional spinal units with disc
      lesions than in the other 2 groups (p < 0.0001). The microcracks were distributed
      predominantly in the vertebral region adjacent to the nucleotomized disc (p <
      0.005). There was a negative association of microcrack density with fractional
      trabecular bone area (R2 = 0.236, p < 0.02). These results support the hypothesis
      that disc degeneration contributes to vertebral fragility by causing microdamage
      accumulation, especially in vertebrae with low bone mass.

PMID- 7634576
TI  - BMP-1 sublocalization on human chromosome 8. Molecular anatomy and orthopaedic
      implications.
AB  - Bone morphogenetic proteins are capable of inducing mesenchymal tissue to form
      mature bone. Bone morphogenetic protein 1 (BMP-1) has a structure unique from the
      other bone morphogenetic proteins and may be involved in activation of other bone
      morphogenetic proteins. Localization of the human BMP-1 gene to chromosome 8 led
      to its consideration as a candidate gene for Langer-Giedion syndrome. Individuals
      with Langer-Giedion syndrome (also known as trichorhinophalangeal syndrome Type
      II) exhibit several skeletal abnormalities, including multiple exostoses and cone
      shaped epiphyses of the hands and feet. The genetic locus responsible for this
      disease has been localized to the long arm of human chromosome 8 at 8q24.1.
      Somatic-cell hybrid and molecular biology techniques were used to sublocalize the
      BMP-1 gene to the short arm of chromosome 8 within the 8p22-cen region. Although
      this locus falls outside the Langer-Giedion syndrome region, and therefore
      excludes BMP-1 as a candidate gene for this disorder, BMP-1 gene sublocalization
      establishes a chromosomal landmark for evaluating other possible disease
      associations with BMP-1.

PMID- 7634577
TI  - The susceptibility of smooth implant surfaces to periimplant fibrosis and
      migration of polyethylene wear debris.
AB  - The purpose of this investigation was to establish whether the tissue response
      and migration of polyethylene debris differed at noncemented smooth and porous
      implant surfaces. This was accomplished through 3 separate but closely related
      studies: (1) a canine cylindrical implant model with smooth and porous surfaces
      exposed to polyethylene debris; (2) a canine total hip arthroplasty model
      analyzing the interface between bone and femoral implants with various porous
      coating configurations; and (3) a histologic analysis of autopsy-retrieved,
      human, noncemented hip prostheses with noncircumferential porous coating. The
      cylindrical implant model involved the placement of split cylinders, 1/2 porous
      and 1/2 smooth, into the distal femur and proximal tibia of 4 dogs. Four control
      implants and 10 test implants (chronically exposed to simulated polyethylene
      debris with a mean size of 4.7 microns) were examined histologically as long as
      30 weeks after surgery. The canine hip study involved the study of 54 noncemented
      hip prostheses at periods of 1, 6, and 24 months. The prostheses possessed 4
      different porous surface configurations: 1 with circumferential porous coating, 2
      with noncircumferential coating, and 1 without porous coating. The human
      retrieval analysis involved the study of 7 cadaveric femora (age, 6 months-5
      years) implanted with a straight titanium-alloy prosthesis possessing proximal
      pads of titanium fiber metal on the anterior, posterior, and medial aspects. With
      all implants in all 3 studies, there was the common finding of bone ingrowth at
      the porous implant surface and a fibrous interface or periprosthetic cavity
      around the portion of the implant that was smooth surfaced. The periprosthetic
      cavity typically was encapsulated by a thin continuous shell of trabecular bone.
      In addition, polyethylene debris was found to have preferentially migrated along
      the smooth implant surfaces. In the longer-term canine and human hip retrievals,
      polyethylene particles in the micron size range were present within histiocytes,
      whereas larger particles as much as 100 microns were found within foreign-body
      giant cells. Of importance for the implants from all 3 studies, with the
      exception of some pronounced cavities on the lateral aspect of the human hip
      prostheses, the periimplant cavities around the smooth surfaces were not
      detectable radiographically. This study clearly established a fundamental
      principle of relative barriers to particulate debris migration. Smooth implant
      surfaces are more susceptible than porous surfaces to the development of a
      fibrous tissue filled periimplant cavity and the subsequent migration of
      polyethylene wear debris.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7634579
TI  - Biomechanical analysis of canine bone lengthened by the callotasis method.
AB  - The mechanical integrity of tibial bone treated by distraction osteogenesis
      (callotasis) using an Orthofix external fixator was evaluated in a group of 6
      dogs. Diaphyseal corticotomies were performed on Day 0. Distraction was begun on
      Day 8, at a rate of 0.33 mm every 8 hours. On Day 34, the Orthofix frame was
      locked. On Day 56, the frames were removed and the dogs were euthanized.
      Radiographs were taken weekly to assess regenerate bone formation and extent of
      tibial bone lengthening, which averaged 12 mm (range, 5-20 mm). One dog showed
      incomplete bony union that was attributed to pin loosening. Torsional testing of
      lengthened and contralateral control tibiae resulted in spiral diaphyseal
      fractures. Five of 6 lengthened tibiae bones fractured within the diaphysis, but
      outside the regenerate area, suggesting that the strength of the lengthened
      segment exceeded that of the original diaphysis which was exposed to stress
      shielding by the external fixator. These observations have led to a method to
      test and evaluate lengthened bone at the time of frame removal and to monitor the
      effectiveness of this type of technique.

PMID- 7634578
TI  - Reaming technique of the femoral diaphysis in cementless total hip arthroplasty.
AB  - Distal fixation enhances initial torsional stability of cementless femoral
      components in primary and revision total hip arthroplasty. Surgical technique
      affects the quality of distal fixation, and too aggressive a technique can cause
      femoral fracture during insertion of the stem. Thirty-five adult human cadaveric
      femoral specimens were implanted with either a standard or long femoral stem.
      Control specimens were reamed 0.5 mm less than the diameter of the distal
      cylindrical portion of the stem and were broached line to line proximally. The
      proximal femur was removed from the remaining specimens to allow assessment of
      distal fixation. The controls outperformed the distal-only fixation groups in all
      testing modes, illustrating that proximal and distal fixation work in concert to
      resist torsional load. The average failure torque in underreamed specimens with
      only distal fixation was 23.6 Nm for standard length stem specimens and 41.3 Nm
      for long stem specimens, whereas the average failure torque for specimens with
      only distal fixation prepared by a line-to-line reaming technique was only 6 Nm.
      The estimated length of tight distal fit should be 10 to 40 mm to obtain
      sufficient initial torsional stability of the stem and still avoid intraoperative
      femoral fracture.

PMID- 7634580
TI  - Effect of elevated temperature on experimental swarm rat chondrosarcoma.
AB  - The effect of hyperthermia on Swarm rat chondrosarcoma viability was investigated
      in Sprague-Dawley rats. The tumor blocks (0.33 g per block) were heated to 40
      degrees C, 50 degrees C, 60 degrees C, 70 degrees C, and 80 degrees C,
      respectively. Blocks that were not heat treated served as controls. Three heating
      sessions (10, 20, and 30 minutes) were performed for each heating group. The
      tumor blocks were transplanted into 4-week-old Sprague-Dawley rats to observe
      tumor growth. The tumor cells of the control, 40 degrees C (3 time sessions), and
      50 degrees C (10 minutes) groups showed little difference from each other
      microscopically before and 5 weeks after transplantation. Microscopic evidence of
      cell destruction was observed immediately after hyperthermia in the groups
      treated at 50 degrees C (20 minutes) and higher. No tumor growth was found in
      these groups 35 weeks after implantation. Type II collagen, the specific collagen
      produced by the tumor, was analyzed with the Northern blot hybridization method.
      The mRNA could not be identified in the groups treated at > 50 degrees C (20
      minutes) at 5 weeks after implantation. This study indicates that the growth of
      Swarm rat chondrosarcoma was retarded at temperatures > 50 degrees C (20
      minutes). The Swarm rat chondrosarcoma is a useful model for studying the effects
      of hyperthermia on malignant tumor growth.

PMID- 7634581
TI  - Lipid extracted bank bone. Bone conductive and mechanical properties.
AB  - Lipid extraction by chloroform methanol previously has been found to increase the
      incorporation of frozen bone allografts. This effect may be because of a
      decreased immunologic response. In the present study, the ingrowth capacity into
      a grafted bone defect was investigated by using the bone harvest chamber model in
      rabbits. In a series of experiments, defatted and frozen allografts were compared
      at 1, 2, and 3 weeks; defatted allografts and defatted autografts were compared
      at 3 weeks; and frozen or defatted allografts and nongrafted defects were
      compared at 3 weeks. Evaluation was performed through histology,
      histomorphometry, and 99mTc-MDP scintimetry. The incorporation was better with
      defatted grafts: by histology at 1 week, mesenchymal tissue filled the
      intertrabecular space in defatted specimens and new bone formation started to
      occur. In contrast, frozen specimens showed a central soft tissue necrosis
      surrounded by inflammatory cells. Histomorphometry showed more new bone and more
      graft resorption in defatted allografts. At 2 and 3 weeks, there was no
      significant difference in new bone area, but at 3 weeks the scintimetric activity
      was higher in defatted allografts, probably caused by an increased remodeling
      rate. Since defatting did not cause increased scintimetric activity in previous
      autograft studies, these findings could indicate that there is a detrimental
      immunologic influence on frozen allografts. There were no differences between
      defatted autografts and allografts. In a second experiment, the biomechanical
      properties of defatted bone were investigated with a compression test on defatted
      and frozen bone cylinders taken from the calf femoral neck. No difference in
      biomechanical properties was found. It was concluded that lipid extraction
      produced a graft that was better incorporated than a nondefatted graft, with no
      loss of mechanical function.

PMID- 7634582
TI  - Effect of sciatic nerve section on neural ingrowth into the rat tibial fracture
      callus.
AB  - Neural influences have been associated with fracture healing through clinical
      observations and experimental procedures. This work was intended to study the
      reliability of sciatic nerve section as a model of denervation of tibial
      fracture. Rats were subjected to a standardized fracture with or without
      simultaneous nerve resection. The fractures were fixed by intramedullary nails,
      and the legs were immobilized to prevent differential loading. On Day 25
      posttrauma, nerve fibers were found in the periosteum, fracture callus, and bone
      marrow space. Most fibers expressed growth-associated protein 43 (GAP-43/B-50),
      suggesting actively ongoing neural regeneration. Additional characterization of
      the type of innervation revealed an extensive distribution of sensory fibers
      containing calcitonin gene-related peptide, a neuropeptide with potent
      vasodilatory actions. Sciatic nerve section reduced all free and some
      perivascular calcitonin gene-related peptide-containing fibers, although
      regenerating nerve fibers still were evident in the bone marrow. Radiographs
      showed an increased callus formation in rats with sciatic nerve section,
      suggesting involvement of neural factors in the healing process. The results show
      that sciatic nerve section is not a reliable model for a total denervation of
      tibial fracture. Hard tissue injury induces proliferation of nerves, probably by
      production of chemotactic factors to attract neural targeting and regeneration of
      injured nerves.

PMID- 7634583
TI  - Long-term results of free vascularized fibular graft. A clinical and radiographic
      evaluation.
AB  - Seven patients who had free vascularized fibular grafts for bone defects > 6 cm
      (mean, 16.6 cm) were studied retrospectively. There were 5 cases of tumor, 1
      pseudoarthrosis, and 1 chronic osteomyelitis. The average followup period was 9.2
      years (range, 5.2-11.3 years). Of the 5 patients with grafts to the lower limb, 1
      showed a 30% reduction in bone width as seen on anteroposterior radiographs,
      whereas 4 patients had increases ranging from 44% to 100% (average, 66%). There
      were 4 graft stress fractures, of which 1 developed eventual shortening of 2.5
      cm. One graft had pseudoarthrosis involving the proximal graft-host junction that
      required secondary procedures with autogenous cancellous bone grafting, with
      eventual limb-length shortening of 5 cm. All other graft-recipient junctions
      healed primarily. The Functional Evaluation Score ranged from 60% to 100% of
      normal function (mean, 85%). Three patients were able to return to sports
      participation. Mild weakness of the extensor hallucis longus in the donor limb
      was observed in 5 patients. Two patients had mild loss of plantar flexion, and 4
      had limitation of dorsiflexion affecting the ankle of the donor limb.

PMID- 7634584
TI  - Gait asymmetry following successful surgical treatment of ankle fractures in
      young adults.
AB  - Forty patients (mean age, 22.8 years) admitted for displaced ankle fracture were
      observed retrospectively to determine by clinical examination and measurement of
      plantar pressure distribution whether successful surgical treatment of ankle
      fractures led to gait symmetry, and whether intraindividual differences were
      related to fracture type and clinical outcome. The mean followup was 18.5 months
      (range, 12-36 months). The deviation of gait was quantified using a symmetry
      index of the total impulse. Using a clinical score, 6 patients had unsatisfactory
      results, and the remaining 34 had satisfactory results. The symmetry index of the
      good (-1.1%) and the poor results (-2.3%) decreased in the range of a healthy
      control group (-0.31%, n = 90), indicating that overall gait symmetry was
      achieved after trauma. The plantar pressure distribution showed significant load
      asymmetries. There was increased loading in the lateral forefoot of the injured
      leg in patients with good results and decreased pressure under the metatarsal
      heads of patients with bad results. Although those asymmetries were related
      neither to fracture type nor clinical outcome, the findings may illustrate
      compensation mechanisms that are used to regain gait symmetry after ankle
      alteration by trauma.

PMID- 7634585
TI  - Natural history of muscle weakness in Friedreich's Ataxia and its relation to
      loss of ambulation.
AB  - From 1979 to 1992, 170 muscular assessments performed on 33 patients with
      Friedreich's Ataxia were reviewed. The average followup was 6 years. All muscle
      evaluations were done by the same team. It was possible to delineate a fairly
      regular and statistically significant pattern of slowly progressive and
      symmetrical loss of strength affecting mainly the lower limbs, and more
      specifically the pelvic girdle muscles. The first significant weakness was
      observed in the hip extensor group, followed in a variable fashion by other
      muscle groups of the lower limb. Upper limb and trunk muscles remained relatively
      spared until late in the disease process, with an overall strength approximately
      80% of normal. Use of a wheelchair began at a mean age of 18.2 years, at which
      time the lower-limb strength averaged 70% of normal. Patients became totally
      unable to walk at a mean of age 20.5 years old, with a further decline in lower
      limb strength to 56% of normal. Weakness does not appear to be the primary cause
      for loss of ambulation in patients with Friedreich's ataxia.

PMID- 7634586
TI  - Hip pain in a 21-year-old man.

PMID- 7634587
TI  - Androgenic regulation of bone mass in women. A review.
AB  - In men and women, androgens and estrogens circulate at levels consistent with
      biologic activity. However, the effects of these steroid hormones on bone
      metabolism were thought to depend on the gender of the individual; that is,
      estrogens were thought to regulate bone mass in women, whereas androgens were
      thought to regulate bone mass in men. It now appears that both of these sex
      steroids influence bone and mineral metabolism in women. Although a number of
      clinical studies have indicated that androgen levels are correlated with bone
      mass measurements in women, it was speculated that androgenic hormones acted on
      bone tissue indirectly. It now has become apparent that androgens act on bone
      tissue through a direct receptor-mediated mechanism that may involve growth
      factor synthesis. The purpose of this review is to examine clinical and basic
      research aimed at elucidating the mechanism of androgen action on bone tissue in
      women.

PMID- 7634588
TI  - The origin of submicron polyethylene wear debris in total hip arthroplasty.
AB  - The microscopic morphology of worn polyethylene surfaces was compared with that
      of the associated polyethylene particles for acetabular cups tested in a wear
      simulator and for cups worn in vivo, using scanning electron microscopy. In the
      absence of significant third-body abrasive damage, the articulation of the ball
      in the cup produced a visually polished surface on the polyethylene. On a micron
      scale, the morphology of the worn polyethylene from in vitro and in vivo wear
      included nodules and fibrils consistent with adhesive, abrasive, and microfatigue
      wear mechanisms. Larger wear features, such as deep scratches or pits measuring
      in 10s of microns, that were seen in the in vivo cups were attributed to third
      body wear. The polyethylene particles isolated from the serum lubricants of the
      wear tests and from the periprosthetic tissues were primarily submicron in size,
      were either rounded or elongated, and were consistent with the submicron wear
      features seen on the cup surfaces. It is the submicron particles that are
      associated with inflammatory periprosthetic bone loss in total hip replacement.
      Although the mean dimensions of the particles generated in vitro were slightly
      smaller than those of the in vivo particles, the overall morphologies were very
      comparable, suggesting that the same lubrication and wear processes were acting
      in the simulator as in vivo.

PMID- 7634589
TI  - Total hip replacement for developmental dysplasia of the hip.
AB  - Total hip arthroplasty relieves pain and improves function for many patients with
      endstage arthritis secondary to developmental dysplasia of the hip. Acetabular
      dysplasia, however, presents a special problem for total hip reconstruction in
      these patients. Structural bone grafting with femoral head autografting to the
      dysplastic acetabulum and cementing acetabular components into the graft provides
      satisfactory short-term results, but longer-term followup data show high
      acetabular component failure rates. At a mean followup period of 7 years, 20% of
      components were loose, and at a mean followup period of 12 years, 46% were loose.
      Noncemented porous-coated hemispherical acetabular components have considerably
      expanded the success of total hip replacement without the need for structural
      bone grafting in such patients. At a mean followup period of almost 7 years, none
      of the acetabular components were reported to be loose in 1 series. For most
      patients, the acetabular dysplasia can be managed by techniques such as reaming
      deeper, using small-diameter porous-coated acetabular components, using screws to
      provide rigid initial stability for the components, increasing the height of the
      prosthetic hip center, and covering small portions of the components with bone
      graft chips if necessary.

PMID- 7634590
TI  - The problem is osteolysis.
AB  - Recent studies have generated considerable information that reveals substantial
      support for major change in the understanding of total hip arthroplasty and its
      current state. Although some of these observations appear unrelated at first
      glance, they can be drawn together to support the thesis that osteolysis is the
      dominant problem in total hip arthroplasty. These observations are as follows:
      (1) Five-year followup data are required for a minimum assessment of a new
      concept in total hip design and material because osteolysis is uncommon before
      that time. (2) Excellent fixation can be achieved on the femoral side with good
      cementing and good cementless techniques. Thus, femoral component loosening is
      less of an issue currently. (3) Many acetabular components become loose because
      of the ingress of particulate debris that leads to linear bone loss at the
      interface with the pelvis, a process that is biologically akin to the more florid
      forms of osteolysis. Thus, much acetabular component loosening represents a form
      of osteolysis. (4) Many cementless femoral reconstructions have developed a high
      incidence of femoral osteolysis. (5) Many cementless sockets have developed a
      high incidence of pelvic osteolysis. Taken in conjunction, these observations
      suggest that periprosthetic osteolysis is the leading problem in contemporary
      total hip replacement.

PMID- 7634591
TI  - The benefits of metal-on-metal total hip replacements.
AB  - The Muller's cast prosthesis with a concentric metal-on-metal articulation and 3
      sliding bearings was used in Switzerland from 1965 to 1967. During the next 10 to
      15 years, a number of hips in which the metal-to-metal systems were implanted
      were revised. Rather than osteoporosis and cranial migration occurring, the
      acetabular roofs were often sclerotic and the components showed no or only minor
      migration. At surgery, the capsule was almost normal and without signs of
      inflammation. Histologically, the capsule did not show the usual masses of giant
      cells associated with polyethylene particles. In the mid-1980s, different designs
      of metal-on-metal articulations were tested. From 1987 to 1990, this author
      developed, together with the biomaterial division of Sulzer Medical Technology, a
      pure titanium shell with a polyethylene-backed 28-mm forged cobalt-chromium liner
      insert. This combination has been successful, with no revisions required to date.
      In summary, with the present metal-on-metal articulations it is now possible to
      stop using the polyethylene. The successful long-term results of the cast cobalt
      chromium metal-on-metal articulations of 1966 hold much promise for the future of
      the new-forged, more-precise, metallic socket.

PMID- 7634592
TI  - Acetabular labrum tears. Diagnosis and treatment.
AB  - An acetabular labrum tear was diagnosed and treated in 56 hips in 55 patients.
      Mechanical hip pain after a relatively minor injury with an associated click
      characterized the history. The tear of the labrum was shown with arthrography in
      88% of the patients. Overall, 89% of the patients were improved by the diagnosis
      and treatment of an acetabular labrum tear: all 7 patients treated nonsurgically
      and 42 of 46 patients treated surgically. In recent years, it has been possible
      to arthroscopically confirm the diagnosis and treat some of these patients.

PMID- 7634593
TI  - The cemented acetabular component of a total hip replacement. All polyethylene
      versus metal backing.
AB  - The increasing use of a cementless acetabular component with a total hip
      replacement requires the need for metal backing, but metal backing with cement in
      the author's use has been less than optimal. The intention, therefore, was to
      evaluate all cemented acetabular components, with and without metal backing, used
      by the author, to offer a standard by which other acetabular components can be
      compared. From 1969 to 1983, 238 Charnley, 141 Mueller, 555 T-28, 100 Miami
      Orthopaedic Surgical Clinic total hip replacements with cemented all-polyethylene
      acetabula, and 134 Miami Orthopaedic Surgical Clinic total hip replacements with
      a cemented metal-backed acetabula were performed and followed from 1 to 22 years.
      The cemented acetabular component failure rates for the Charnley, T-28, and all
      polyethylene Miami Orthopaedic Surgical Clinic were 14%, 10%, and 9%,
      respectively. There was a 20% failure rate in the Mueller and metal-backed Miami
      Orthopaedic Surgical Clinic acetabular components. The Charnley (p < 0.0001), T
      28 (p < 0.0001), all-polyethylene Miami Orthopaedic Surgical Clinic (p < 0.0001),
      and Mueller (p < 0.012) total hip replacements demonstrated statistically
      improved survival rates as compared with the metal-backed Miami Orthopaedic
      Surgical Clinic acetabular components. The Charnley (p < 0.0001) and T-28 (p <
      0.0003) sockets survived statistically better than the Mueller sockets.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7634594
TI  - Concerns and improvements with cementless metal-backed acetabular components.
AB  - The relatively high incidence of acetabular component failure shown in long-term
      followup studies of cemented total hip replacement has led to the use of
      noncemented fixation on the acetabular side of the total hip arthroplasty. In the
      first generation of noncemented acetabular devices, large-size femoral heads
      requiring thinner polyethylene were used with many of the popular designs. These
      components were also modular, but the design considerations involved in
      minimizing polyethylene debris were not fully appreciated. The newer designs of
      noncemented acetabular components are addressing the need to minimize wear and
      the production of particulate debris at the bearing surface and metal
      polyethylene interface. Newer techniques also have been developed to provide
      initial component stability and bone-prosthesis contact. With these improvements,
      the results of noncemented acetabular fixation may outperform the results with
      cemented fixation. This may be especially true when considering the ease of
      insertion and versatility of noncemented acetabular components.

PMID- 7634595
TI  - Titanium as the material of choice for cementless femoral components in total hip
      arthroplasty.
AB  - Modern total hip arthroplasty has been performed using femoral stems manufactured
      from stainless steel, cobalt-chrome molybdenum alloy (CoCrMb), titanium aluminum
      vanadium alloy (TiAlV), and, on a limited basis, low-elastic modulus composites.
      Today, only CoCrMb and TiAlV are used in significant numbers. There is ample
      theoretical, experimental, and clinical evidence to support Ti-AlV as the
      material of choice for cementless femoral stems, based on superior mechanical
      compatibility and biocompatibility. The primary advantage of TiAlV over CoCrMb is
      a lower modulus of elasticity. This results in decreased stress shielding and
      subsequent favorable femoral remodeling. This effect is more significant with the
      smaller stem sizes used in primary surgery but persists even with larger stem
      sizes used in revision surgery. The second advantage of TiAlV is its
      biocompatibility. Titanium aluminum vanadium alloy is of relatively low toxicity
      in concentrations found clinically, and TiAlV is inert in the physiologic
      environment. With regard to fixation in cementless total hip arthroplasty, TiAlV
      has been shown to achieve excellent bone ingrowth into porous surfaces. In
      addition, there is evidence of superior bony ingrowth into TiAlV as compared with
      CoCrMb. Titanium aluminum vanadium alloy is presently the material of choice to
      be used in conjunction with hydroxyapatite coating. Prosthetic design, stem
      diameter, and porous-coating applications play significant roles in bony response
      regardless of metal composition.

PMID- 7634596
TI  - The tradeoffs associated with modular hip prostheses.
AB  - In an effort to gain greater insight into the tradeoffs associated with modular
      hip prostheses, 2 approaches were taken. A questionnaire was sent to each of the
      orthopaedic implant manufacturing companies asking specific questions regarding
      modular components, and a series of retrieved prostheses, both modular and
      nonmodular, were examined to determine the potential sources of problems
      associated with modular connections. The respondents to the questionnaire
      generally agreed that it was more expensive to produce modular prostheses due to
      the required tolerances at the modular connections, and that the increased
      flexibility provided by the modularity was important to surgical outcome. There
      was less consensus on whether inventories were reduced and little data to support
      any improvement in surgical outcome caused by modularity. The most frequent
      problems associated with modular connections were fretting and corrosion. Easily
      observable significant fretting occurred in 4% of 701 head/neck tapers. Corrosion
      was observed in > 30% of the mixed-alloy head/stem combinations, in < 10% of all
      titanium-alloy modular components, and in < 6% of all-cobalt-alloy devices. In 1
      series of retrieved modular femoral components (15 titanium alloy and 15 cobalt
      alloy) with both sets having approximately the same duration of implantation, 7%
      of the all-cobalt-alloy components had corrosion, whereas 33% of the mixed-alloy
      components had corrosion.

PMID- 7634597
TI  - Predicting pathologic fracture risk in the management of metastatic bone defects.
AB  - Guidelines for the prediction of pathologic fracture would facilitate the
      management of patients with metastatic bone defects. Unfortunately, existing
      clinical guidelines have not been validated, often run counter to engineering
      practice, and do not accurately predict the risk of fracture for many patients.
      To serve as a basis for improved guidelines, a factor of risk for a pathologic
      fracture is defined as the load applied to a bone divided by the load at which
      the bone fails. Failure loads for bones with metastatic defects have been
      measured in vitro, and depend on defect geometry, bone properties, and the type
      of loading. For a diaphyseal defect that destroys 50% of the cortex, strength
      reductions of between 60% and 90% can occur. The load-bearing capacity of a long
      bone with a diaphyseal defect also can be predicted using computer models if the
      geometry of the defect and properties of surrounding bone are known. Similarly,
      new methods that apply basic engineering principles to computed tomography data
      allow prediction of the load-bearing capacity of vertebrae with simulated
      defects. By contrast, the data presented here suggest that by using plane
      radiographs or computed tomographic (CT) examinations, experienced orthopaedic
      surgeons cannot accurately estimate the strength reductions or load-bearing
      capacity for proximal femurs with intertrochanteric defects. By combining new
      methods to predict the load-bearing capacity with estimated loads for activities
      of daily living, it is possible to calculate a factor of risk for pathologic
      fractures.

PMID- 7634598
TI  - Orthopaedic management of extremity and pelvic lesions.
AB  - Bony metastases are ubiquitous in patients with advanced cancer, and pathologic
      fractures may occur within either lytic or blastic foci. Approximately 90% of
      such fractures that require surgical intervention occur in the femur, humerus, or
      periacetabular pelvis. Techniques for internal fixation or prosthetic replacement
      have been designed with the realization that destructive bony lysis often extends
      well proximal and distal to the actual fracture site, and bony union will not
      occur after irradiation unless absolutely rigid fixation is achieved.
      Intramedullary fixation using some type of interlocking device, either proximally
      or distally, is preferable to extramedullary fixation of fractures. The mean
      postfracture survival for most patients is approximately 2 years.

PMID- 7634599
TI  - Orthopaedic management of spinal metastases.
AB  - Spinal metastases result in severe spinal pain, neurologic deficits, or both.
      These symptoms usually are caused by spinal instability, in which conservative
      therapy can have no effect, and surgical treatment is required to restabilize the
      destroyed spinal segments. Surgical indications are instability of the spine,
      pain and/or paresis resistant to radiation therapy, acute progressing paresis,
      and unknown histologic diagnosis. There are 2 surgical approaches for vertebral
      metastases: prosthetic replacement and posterior stabilization. Single or 2
      consecutive diseased vertebrae should be treated with replacement surgery. In
      this series, excellent surgical outcome was attained with this procedure, and
      surgical benefit was maintained until the terminal stage of each patient.
      Multiple vertebral metastases are treated with posterior stabilization using
      various instrumentation systems that provide rigid stabilization. To choose the
      most appropriate procedure for each patient, the local condition of the lesion
      and general status of the patient, including prediction of life expectancy,
      should be evaluated fully. Spinal metastases develop early and are not terminal
      events. Therefore, not only palliative treatment but also surgical intervention
      should be considered for spinal metastases when indicated.

PMID- 7634600
TI  - Orthopaedic management using new devices and prostheses.
AB  - The goals of treatment for patients with metastatic disease are control of pain
      and maintenance of function. Prosthetic arthroplasty is a useful technique for
      selected indications. Specific indications include (1) reconstruction of large
      destructive areas that are not amenable to internal fixation, (2) salvage of
      failed internal fixation devices, and (3) salvage of lesions in which there are
      no radiotherapy options to prevent disease progression. Custom modular devices
      allow resection of varying segments of the skeleton. Immediate rigid fixation is
      achieved with cemented intramedullary stems. Patients are allowed to bear full
      weight as tolerated immediately postoperatively. A custom modular diaphyseal
      segmental replacement system allows resection of large diaphyseal lesions and
      immediate fixation. The complication rate is low after arthroplasty.

PMID- 7634601
TI  - Methotrexate loaded acrylic cement in the management of skeletal metastases.
      Biomechanical, biological, and systemic effect.
AB  - Skeletal metastases occur commonly, and frequently are complicated by the
      development of an impending or pathologic fracture. In the majority of instances,
      these patients are best treated by internal stabilization, frequently
      supplemented by methylmethacrylate, to relieve pain and maintain the patient's
      mobility. The underlying tumor may continue to grow, and if this occurs the
      progressive lysis may result in loosening and subsequent failure of the implant.
      To prevent additional local growth, postoperative radiotherapy is recommended,
      and many patients also receive endocrine or chemotherapy, but the adjuvant
      therapy is not always successful in preventing progressive local tumor induced
      osteolysis. It is possible that the addition of chemotherapeutic agents to the
      methylmethacrylate may inhibit local growth. This study was performed to
      determine the biomechanical, biologic, and systemic effects of adding
      methotrexate to methylmethacrylate. The results show that the addition of
      methotrexate in as much as a concentration of 2 g methotrexate per 40 g cement
      did not significantly alter the biomechanical characteristics of the bone cement.
      The incorporated methotrexate was released continuously from the loaded bone
      cement, and in the amount and concentration used did not have any toxic effects
      on the host animal. The methotrexate did not appear to be affected by the heat of
      polymerization and had a significant systemic effect. There was a significant
      reduction in pulmonary metastases with methotrexate loaded cement as compared
      with unloaded cement, the effect being dependent on the concentration of
      methotrexate in the cement. The results of these studies indicate that
      methotrexate loaded cement may have an important role to play as part of the
      orthopaedic management of impending and pathologic fractures.

PMID- 7634602
TI  - Tumor-bone interactions in skeletal metastasis.
AB  - Bone metastases are a frequent clinical problem in patients with breast,
      prostate, and other cancers. Formation of these lesions is a site-specific
      process determined by multiple cellular and molecular interactions between the
      cancer cells and the bone microenvironment. Clinical studies, and in vivo and in
      vitro experimental approaches, have been useful to dissect different stages of
      this process. Mechanisms identified as relevant to cancer spreading and tumoral
      growth in the bones include (a) early vascular spread of cancer cells to bones;
      (b) adhesion of cancer cells to the bone microvasculature and matrix components;
      (c) presence of growth factors and chemo-attractants in bone; (d) osteolysis by
      osteoclasts, tumor associated macrophages, and cancer cells; and (e) tumor
      induced local osteoblastic proliferation. Although none of these mechanisms alone
      are responsible for the development of bone metastases, their investigation may
      lead to novel therapeutic approaches that specifically block these stages and,
      thus, may hinder development of bone metastasis. The use of bisphosphonates and
      other experimental strategies already is being tested in clinical trials.

PMID- 7634603
TI  - Rehabilitation of cancer patients with skeletal metastases.
AB  - Complications of cancer that are amenable to treatment with rehabilitation
      techniques will develop in many patients with skeletal metastases. This treatment
      can be given safely, with a low prevalence of pathologic fracture. Many patients
      with skeletal metastases and pathologic fracture have been shown to be good
      candidates for intensive rehabilitation programs if they do not have
      hypercalcemia caused by lytic metastases or pain severe enough to require
      parenteral narcotics.

PMID- 7634604
TI  - Skeletal metastases.

PMID- 7634605
TI  - Use of distraction arthroplasty in unstable fracture dislocations of the elbow.
AB  - Patients with persistent instability after experiencing posterior dislocation of
      the ulnohumeral joint associated with large unstable fractures of the coronoid
      process of the ulna can be challenging to manage. To date, no reports have
      documented an effective treatment program for this injury. Joint stiffness or
      persistent instability results in most cases. Seven patients are discussed who
      were treated with a joint distraction device. Six (86%) of the 7 patients had
      successful outcomes at a minimum followup of 2 years. The mean arc of flexion
      before surgery was 33 degrees; after surgery, the arc increased to 88 degrees.
      The joint distraction device provides immobilization of periarticular fractures
      and simultaneously allows for joint movement, which results in a stable and
      mobile joint. Without this device, a 20% satisfactory result for this injury was
      reported; this percentage improved to 86% by rendering the joint stable with
      adequate motion.

PMID- 7634606
TI  - Hydroxyapatite-coated hip prostheses. Early results from an international study.
AB  - A hydroxyapatite-coated hip prosthesis designed to stimulate proximal femoral
      stress transfer was studied in 222 patients undergoing primary total hip
      arthroplasty with a minimum followup of 2 years. The femoral component was a
      roughened titanium alloy with a 50-mu coating of hydroxyapatite applied to the
      proximal third. A proximal press-fit technique was applied with distal femoral
      over-reaming as standard procedure. The hydroxyapatite-coated acetabulum was of
      hemispherical design. Analysis of the clinical results showed a mean Merle
      D'Aubigne score of 16.7 points at 6 months and 17.4 points at 2 years. Mild
      residual thigh pain of unknown origin was reported in 3.6% of patients at 2
      years. Radiographic evaluation showed complete acetabular and proximal femoral
      osseointegration without any loosening. No radiolucency or reactive line
      formation was observed around the hydroxyapatite-coated areas of the prostheses.
      Femoral bone densification occurred at the coated-uncoated transition zone (54%);
      4% to 6% of cases showed cortical hypertrophy at the uncoated area of the stem.
      Reactive lines were seen around the distal stem in 52% of patients after 2 years.
      The clinical outcome was excellent, and the radiographic data pointed mainly to
      proximal femoral stress transfer.

PMID- 7634608
TI  - Median nerve entrapment after dislocation of the elbow in children. A report of 2
      cases and review of literature.
AB  - Median nerve injury after elbow dislocation is uncommon. Reported are 2 cases of
      median nerve paralysis caused by entrapment within the elbow joint. For both
      patients, the diagnosis was made several months after the injury at surgical
      exploration. This complication occurs almost exclusively in the skeletally
      immature. A median nerve deficit after reduction of an elbow dislocation in
      children, especially when associated with a medial epicondylar fracture, should
      be an indication for surgical exploration and release of the entrapped nerve.

PMID- 7634609
TI  - Hip fractures in adults younger than 50 years of age. Epidemiology and results.
AB  - A review of the records of 3147 patients with hip fractures admitted to the
      authors' institution during a 5-year period revealed that 95 (3%) patients were
      aged 50 years or less at the time of fracture. Of patients between the ages of 20
      and 40 years, hip fracture most commonly occurred in men after high-energy
      injuries. These injuries commonly occurred in the subtrochanteric and
      basicervical regions, or as a vertical transcervical fracture. In contrast, most
      patients between 40 and 50 years of age were medically frail and sustained
      osteoporotic-type fractures during simple falls. A treatment protocol of early
      reduction followed by internal fixation was evaluated in 75 nonpathologic
      fractures. At a mean of 25 months, fracture union with a good or satisfactory
      functional outcome was found in 57 (76%) patients, and 5 (7%) patients died of
      unrelated medical problems. Complications of primary treatment developed in 16
      (21%) patients, but only 13 (17%) revision procedures were required. A
      satisfactory functional outcome was found in 10 patients who had uncomplicated
      revision surgery, but there were poor functional results in the 3 who required
      tertiary surgery. Despite the previously reported poor results of treatment of
      hip fracture in young adults, these results demonstrate that satisfactory results
      can be achieved with early, accurate fracture reduction followed by rigid
      internal fixation.

PMID- 7634607
TI  - A case of steroid-induced osteonecrosis of femoral condyle treated surgically.
AB  - The clinical course and the established treatment for steroid-induced
      osteonecrosis of the femoral condyle have not been clarified yet, mainly because
      of the limited number of reports. Conservative treatment for steroid-induced
      osteonecrosis of the femoral condyle has been advocated, because the underlying
      disease tends to be serious and multiple joints are usually involved.
      Conservative treatment usually is continued until osteonecrosis becomes extensive
      and osteoarthritis has progressed enough to justify total knee arthroplasty.
      Reported here is a case of steroid-induced osteonecrosis of the lateral femoral
      condyle that, according to preliminary results, was treated successfully with a
      vascularized bone and periosteal graft.

PMID- 7634610
TI  - Bone mineral density changes in distracted callus stimulated by pulsed direct
      electrical current.
AB  - To evaluate the effect of application of pulsed direct current electrical
      stimulation to callus tissue, a 1-cm bone-lengthening model using an external
      lengthener was applied to rabbit tibia. Twenty-microampere pulsed direct current
      was applied 12 hours daily from the day of osteotomy until 40 days after the
      completion of lengthening. The area, bone mineral content, and bone mineral
      density of the distracted callus and of the proximal and distal segments of the
      tibia were evaluated using dual-energy xray absorptiometry. The absolute and
      relative values of bone mineral density of the electrically stimulated callus
      were significantly increased as compared with those in the control group. Pulsed
      direct current electrical stimulation may be indicated in bone lengthening to
      stimulate the poorly mineralized callus, and may shorten the overall time course
      of leg lengthening.

PMID- 7634611
TI  - Effect of age on bone formation around orthopaedic implants.
AB  - Bone and mineral metabolism are known to change with age, but studies of biologic
      fixation have traditionally ignored or poorly documented the effect of age on the
      quality and quantity of bone about implants. This study documents the effect of
      age on quality and quantity of biologic fixation about hydroxyapatite-coated and
      uncoated implants in young and old sheep. Mechanical and histologic tests
      demonstrate comparable fixation of implants in young and old sheep, indicating
      that age is not a dominant factor in the development or failure of implant
      osseointegration.

PMID- 7634612
TI  - Cement penetration with pulsed lavage versus syringe irrigation in total knee
      arthroplasty.
AB  - Twelve total knee arthroplasties were performed on 12 patients who had
      osteoarthritis. The freshly resected tibial plateaus and femoral condyles were
      divided in 2, and each half was subjected to different methods of preparation.
      One half of the specimen was irrigated with saline with a standard bulb syringe,
      while the other half was irrigated with pulsed lavage. Cement then was
      pressurized into the cut surfaces. Sections were analyzed using the Image
      Analysis Software Morphometry System. A significant increase in cement
      penetration and decrease in bone debris were found in pulsed lavage specimens as
      compared with controls (p < 0.05). The penetration of cement in total knee
      components can be significantly increased by using pulsed lavage of the
      cancellous surfaces.

PMID- 7634613
TI  - A cadaveric and radiologic assessment of catheter placement for the measurement
      of forearm compartment pressures.
AB  - The diagnosis of compartment syndrome is essentially a clinical one. In recent
      years, much interest and research has focused on the development of
      intracompartmental pressure monitoring devices to help in the diagnosis of this
      condition. Proper placement of the catheter is essential for accurate monitoring,
      because an incorrect result is potentially more dangerous than no reading at all.
      In the forearm, measurement in the flexor digitorum profundus is thought to be a
      more sensitive way of assessing rising pressure. One of the risks of catheter
      placement is inadvertent damage to a neurovascular structure, particularly when
      monitoring pressures in deeper muscle bellies. Standard anatomic texts and
      outpatient magnetic resonance scans of the forearm were studied to define a safe
      pathway for the introduction of a catheter into the volar forearm. An approach
      from the midline to the ulna, between the tendons of the flexor carpi radialis
      and palmaris longus, seemed the safest. Ten cadaveric forearms had 100 cc of
      gastrograffin injected into the deep forearm through a dorsal approach. The
      median and ulnar nerves were cannulated with a fine wire from the elbow to the
      wrist. Two cannulae were passed, using the suggested approach, at 2 locations
      between the wrist and the mid forearm. All limbs then were scanned with computed
      tomography, and the images were reviewed. In all forearms, the cannulae passed
      between the median and ulnar nerves into the belly of the flexor digitorum
      profundus and posed no risk to the neurovascular structures.

PMID- 7634614
TI  - Hip pain in a 24-year-old woman.

PMID- 7634616
TI  - The function of the vertebral veins and their role in the spread of metastases.
      1940.

PMID- 7634615
TI  - Facilitation and suppression of bone metastasis.
AB  - Most patients with cancer die because the cancer metastasizes to other organs.
      Bone is 1 of the 3 most common sites of tumor metastasis, and is a catastrophic
      complication of cancer, because it is associated not only with intractable pain,
      but also with other morbidity that usually hastens an uncomfortable death.
      Despite its importance, to date no specific therapies to prevent this
      complication of cancer or treat it once it occurs have been demonstrated. In this
      article, current understanding of the processes involved in the pathophysiology
      of bone metastasis will be reviewed, and approaches aimed at preventing the
      development of a bone metastasis and treating bone metastasis once it has
      occurred will be discussed.

PMID- 7634617
TI  - Development of skeletal metastases.
AB  - Skeletal metastases result from a series of complex steps including activation of
      osteoclasts and interaction between adhesion molecules on cancer cells and bone
      matrices. Researchers of this study used pathologic specimens of breast cancer
      cells from primary and metastatic sites obtained at surgery or autopsy to
      demonstrate the expression of parathyroid hormone-related protein by
      immunohistochemistry and beta 3 integrin by in situ hybridization to clarify the
      role of tumor-derived osteoclast activating factors and adhesion molecules in the
      development of skeletal metastases. The results of this retrospective study
      showed a significant difference of parathyroid hormone-related protein and beta 3
      integrin expression in cases with and without skeletal metastases. These
      expressions were enhanced or clonally selected or both in skeletal metastatic
      sites. Because activation of osteoclastic bone resorption by parathyroid hormone
      related protein could facilitate tumor cells to attach to the eroded bone surface
      through cell adhesion molecules, these 2 factors could make it easier for tumor
      cells to grow in bone.

PMID- 7634618
TI  - Hypercalcemia and bone resorption in malignancy.
AB  - Hypercalcemia is the most common paraneoplastic syndrome associated with cancer.
      This paper addresses the etiology and pathogenesis of hypercalcemia of malignancy
      and discusses the relative contributions of local and humoral effects on bone and
      renal calcium homeostasis. The roles of parathyroid hormone-related protein and
      other osteolytic cytokines are outlined. New biochemical markers that enable more
      specific monitoring of the response of bone metastases to treatment are
      introduced, including urinary excretion of the collagen crosslinks pyridinoline
      and deoxypyridinoline. The clinical management and prevention of hypercalcemia is
      systemically outlined, including indications for bisphosphonate, glucocorticoid,
      and calcitonin therapy. The results of recent trials of bisphosphonate therapy
      for the prevention of tumor progression and its subsequent problems such as bone
      pain, fracture, and hypercalcemia also are discussed.

PMID- 7634619
TI  - Diagnosis of skeletal metastases and assessment of response to treatment.
AB  - Skeletal metastases occur commonly, and it is important to diagnose them early if
      the patient is to receive optimum treatment. The diagnosis of the lesion should
      include not only the site of the lesion and the degree and site of dissemination,
      but also the presence of any complications; the extent of soft tissue
      involvement, particularly with spinal metastases; and the vascularity of the
      lesion. The staging of the cancer may be important before starting treatment.
      Response to treatment should be assessed objectively, and as early as possible,
      so that if a patient has failed to respond, treatment can be altered. Many
      methods are available for the diagnosis of skeletal metastases and the assessment
      of their response to treatment. These methods are discussed in this article.

PMID- 7634620
TI  - Magnetic resonance imaging of metastatic bone disease.
AB  - Traditional imaging methods used in the detection and evaluation of metastatic
      bone disease lack either sensitivity (plain radiography) or specificity (bone
      scintigraphy). Magnetic resonance imaging now has been shown to be the most
      sensitive imaging technique available for the detection of bone metastases. On T1
      weighted images bone metastases tend to stand out as focal or diffuse hypointense
      (dark) lesions against a background of higher-signal-intensity marrow. Use of fat
      suppression techniques may further increase the conspicuity of metastatic
      lesions. Magnetic resonance imaging is unlikely to replace bone scintigraphy as
      an initial screening technique for bone metastases because scintigraphy can image
      the whole skeleton quickly and at relatively low cost. Magnetic resonance is
      particularly useful for imaging the spine because vertebral bodies, paraspinal,
      and intraspinal soft tissues can be evaluated, providing a noninvasive method of
      detection of spinal cord compression. Magnetic resonance imaging also is useful
      in discriminating between benign and malignant vertebral collapse.

PMID- 7634621
TI  - Prognostic significance of bone metastasis from breast cancer.
AB  - There is no established method for assessing the prognosis of patients with
      breast cancer and metastasis confined initially to bone. The medical records of
      82 patients with breast cancer nad metastasis confined initially to bone were
      reviewed. The following variables were analyzed at the time when bone metastasis
      was first diagnosed, to determine their relationship to length of survival:
      distribution of metastatic bone lesions on bone scan, presence of radiographic
      osteosclerosis in metastatic bone lesions, menstrual status, and disease-free
      interval. Univariate and multivariate analyses revealed that the distribution of
      metastatic bone lesions and the presence of radiographic osteosclerosis in these
      lesions were significant predictors of survival. Premenopausal or late
      postmenopausal status, and longer disease-free intervals (> or = 24 months) or no
      disease-free intervals (Stage IV breast cancer and metastasis confined to bone at
      the time of cancer diagnosis) showed a trend, although not statistically
      significant, toward longer survival. Distribution of metastatic bone lesions on
      bone scan and the presence of radiographic osteosclerosis in metastatic bone
      lesions should be considered prognostic variables for patients with breast cancer
      and metastasis confined initially to bone.

PMID- 7634622
TI  - Functioning free muscle transplantation for brachial plexus injury.
AB  - Sixty-four cases of functioning free muscle transplantation to reconstruct
      brachial plexus injuries were reviewed for the years 1986 to 1991. Results were
      assessed using the Medical Research Council grading system, and success was
      defined as a muscle strength rating of 4 (ability to lift at least 1 kg).
      Functioning free muscle transplantation for shoulder abduction was ineffective
      because of its complex requirements. Functioning free muscle transplantation for
      biceps replacement using 2 or 3 intercostal nerves for innervation is a
      recommended procedure (success rate, to 80%). For function below the elbow, an
      intercostal nerve or spinal accessory (XI) nerve to innervate the functioning
      free muscle transplantation in flexor digitorum profundus replacement was
      inadequate. A new strategy for functions below the elbow was developed as a
      staged operation. The first operative stage involved either transfer of the
      ipsilateral upper trunk (in cases with lower plexus avulsion injury associated
      with upper trunk rupture) or contralateral C7 spinal nerve (in cases with total
      root avulsion injury) to the selected paralytic nerve. The second stage involved
      functioning free muscle transplantation, such as biceps or flexor digitorum
      profundus replacement for special function. No functioning free muscle
      transplantation for triceps or intrinsic hand function was tried.

PMID- 7634623
TI  - Microsurgery in children.
AB  - Advances in microsurgical techniques have permitted replantation and
      reconstructive procedures to restore amputated or injured parts with a high
      degree of success in children. Despite this progress, some technical concerns
      remain. During a 15-year period, replantations were done in 53 children with
      major limb (18), hand (10), or digit (25) amputations. Even in patients with
      crush or avulsion injuries, the results suggest that replantation procedures are
      justified considering the superior recuperative ability in children. Free tissue
      transfer was used for reconstructive procedures in 26 children, including free
      flaps, vascularized bone transfers, nerve grafts, and toe-to-thumb transfers. The
      microsurgical success rate was 86.8% for replantation procedures and 96% for
      reconstructive procedures. Although the technical aspects and outcome of
      replantation attempts still differ between adults and children, there appears to
      be little difference in free tissue transfer. Thus, most replantation and
      reconstructive procedures can be attempted with a high possibility of success in
      children.

PMID- 7634624
TI  - Pathophysiology and related studies of the no reflow phenomenon in skeletal
      muscle.
AB  - Although the success rate of microvascular replantation and revascularization
      procedures has increased steadily since the 1960s, some replanted tissues do not
      reperfuse despite technically adequate arterial anastomoses. This failure of
      microvascular perfusion is termed no reflow. Much research has been directed
      toward discovering the etiology of no reflow since it was first described 25
      years ago. Three pathophysiologic processes have been identified as playing a
      central role in the development of no reflow: intracellular calcium overload,
      oxygen-free radical medicated damage, and altered arachidonic acid metabolism.
      The first tissue believed to be injured irreversibly by these processes is the
      endothelium, which leads to dysfunction of the parenchymal cells. All 3 pathways
      are interrelated extensively, which allows for pharmacologic intervention at many
      different steps. Agents that have been shown to be beneficial in preventing no
      reflow include calcium channel blockers, prostaglandin analogs, thromboxane
      synthesis inhibitors, vasodilators, thrombolytics, and many antioxidants.
      Although they have been shown to be effective in various laboratory models,
      additional investigation is necessary before these treatments can be established
      in clinical use.

PMID- 7634625
TI  - Free gracilis muscle transplantation for hand reconstruction.
AB  - Free muscle transplantation with motor innervation is the only way to add
      contractile elements to upper extremities with extensive loss of musculature due
      to direct trauma or untreated compartment syndrome (Volkmann's contracture). The
      functional cross-sectional area and the mean resting fiber length determine the
      maximum power and the contracting amplitude of the donor muscle, respectively.
      Although considerably weaker than the finger flexors to be replaced, the gracilis
      muscle was the preferred donor muscle because of the consistent anatomy of its
      neurovascular pedicle and the minimal donor site morbidity. In a series of 15
      gracilis transplantations, all 13 muscles that survived regained function. Finger
      motion was dependent on the preoperative condition of tendons and joints. Even
      after complete loss of the flexor and extensor compartment after direct trauma or
      infection, a useful upper extremity could be restored, which was preferable to
      the only alternative--amputation.

PMID- 7634626
TI  - Repair of complete acromioclavicular separations using the acromioclavicular-hook
      plate.
AB  - Complete Tossy III acromioclavicular separations in 21 male patients (according
      to the Rockwood classification: 7 Type III and 14 Type V lesions) with a mean age
      of 31 years were treated by surgical repair with the acromicroclavicular-hook
      plate within a period of 6 years. The population consisted of 18 patients with
      acute injuries and 3 with old injuries. Six patients experienced infections and
      delayed wound healing; osteitis did not occur. In 1 case, delayed wound healing
      was combined with dislocation of the hook. Bending of the implant occurred in
      another patient. Sixteen patients underwent clinical and radiographic followup at
      a mean of 38 months. Four patients who had no complications and free mobility of
      the shoulder joint at the end of treatment after removal of the implant did not
      appear for followup. One patient died of a malignant brain tumor. According to a
      modified evaluation system by Poigenfurst et al, clinical and radiographic
      findings showed 8 excellent, 7 good, and 1 poor result. A secondary widening of
      the hook hole in the acromion was seen in 13 patients; this was related to the
      large range of motion of the acromioclavicular joint. Calcifications and
      ossifications in the coracoclavicular ligaments, diastases in the
      acromioclavicular joint, and redislocations were not significantly different when
      this method was compared with other surgical techniques as reported in the
      literature. Use of the acromioclavicular-hook plate permits retention in the
      transverse plane without impairing the joint itself, but the technique is
      challenging.

PMID- 7634628
TI  - The effect of wrist deviation on grip and pinch strength.
AB  - The effect of wrist deviation on grip and pinch strength was evaluated in 12
      normal right-handed adults. Wrist positions of neutral, maximal ulnar (average,
      41 degrees), and maximal radial deviation (average, 26 degrees) were held in
      short-arm casts while grip and key and tip pinch were measured. Wrist position
      was neutral with respect to flexion and extension. A highly significant effect of
      wrist deviation on grip strength was found (p < 0.0001). The effect on pinch
      strength was not statistically significant. Wrist deviation deformities arise in
      several clinical situations, such as radial clubhand and malunions of the distal
      radius. A loss of grip strength was found in radial deviation in this study. This
      would support 1 of the premises for surgical correction of such deviation by
      centralization or osteotomy.

PMID- 7634627
TI  - Electromyographic recordings in shoulder muscles during eccentric movements.
AB  - The purpose of the present study was to investigate shoulder muscle activity
      during eccentric muscle movements, and to determine whether electromyograms in
      patients with joint laxity differed from those in normal subjects. Five normal
      subjects and 6 patients with generalized joint laxity and shoulder instability
      were studied. Both shoulders were investigated. Normalized electromyograms were
      recorded during eccentric loaded movements from 8 shoulder muscles in parallel.
      Intra-muscular fine wire electrodes were used for 3 muscles of the rotator cuff:
      subscapularis, supraspinatus, and infraspinatus. Surface electrodes were used for
      superficially located muscles: the anterior, middle, and posterior parts of the
      deltoid, pectoralis major, and latissimus dorsi. A general trend was an
      activation of several muscles rather than a single muscle during all movements
      investigated. Patients with generalized joint laxity activated their
      supraspinatus and subscapularis muscles to a higher level during flexion and
      adduction movements than normal subjects did. This might indicate a greater
      necessity for muscular activity to provide anterior shoulder stability in lax
      joints. Compared with concentric movements previously studied, results from this
      study showed that the magnitude of activation was significantly lower during
      eccentric movements in normal subjects and in patients with joint laxity.

PMID- 7634629
TI  - Femoral bone loss following hip replacement. A comparative study.
AB  - Fifty femoral stems of 5 different types were compared with respect to bone
      retention in the proximal femur at least 3 years after implantation. Dual energy
      x-ray absorptiometry scans were used to compare bone mineral density in the
      medial neck of the replaced hip with that of the other hip where surgery had not
      been performed. Bone mineral density declined on average of 57% with the cemented
      straight stem Mueller prosthesis and 34% for the uncemented Anatomic Medullary
      Locking prosthesis. For the cemented Harris Precoat prosthesis, the decline in
      bone mineral density was 43%. Two uncemented implants with horizontal platform
      type collars showed an average decline in bone mineral density of 8% and 14%.
      Clinically, all the stems functioned well, and excellent implant insertion
      technique had been used. The decline in bone mineral density was evident on plain
      radiographs. The decrease in bone mineral density paralleled the known decrease
      in the medial neck strain. This study suggests that more proximal bone will be
      maintained by implants that load the proximal femur in as physiologic a fashion
      as possible.

PMID- 7634630
TI  - Ketorolac prophylaxis against heterotopic ossification after hip replacement.
AB  - Three hundred three patients undergoing total hip replacement were enrolled in a
      prospective, randomized, double-blind clinical study of heterotopic bone
      formation. All the procedures were primary arthroplasties done for osteoarthritis
      using an anterolateral approach. Patients with spondyloarthropathy, previous
      surgery, or previous head or pelvic trauma were excluded. A total of 152 patients
      received 60 mg of ketorolac intraoperatively and 30 mg every 8 hours for 5 doses
      postoperatively; another 151 patients received no prophylaxis for heterotopic
      bone formation. Patients in each group had similar postoperative courses. No
      complications related to ketorolac use were seen. There was significantly less
      heterotopic bone formation in the ketorolac-treated group. Severe heterotopic
      bone formation did not develop in any treated patient, as compared with 11
      untreated patients. It is concluded that ketorolac is useful as prophylaxis to
      prevent heterotopic bone formation. Treatment with ketorolac is completed during
      hospitalization; therefore, compliance is ensured. This treatment is convenient,
      but not necessarily more effective than other treatments.

PMID- 7634631
TI  - Naproxen for 8 days can prevent heterotopic ossification after hip arthroplasty.
AB  - The effect of 1 week of treatment with naproxen on the formation of heterotopic
      ossification after cemented total hip arthroplasty was studied in a prospective
      trial. Twenty-seven patients received 500 mg naproxen twice daily for 7 days
      postoperatively. The medication was started on the morning of the operation. The
      results were compared with a control group of 23 patients from a previous study
      who had not received any type of non-steroidal antiinflammatory drug. All
      radiographs were mixed randomly, and patient identification was blinded. Three
      months after the operation, heterotopic ossification had developed in 12 (52%)
      patients in the control group and in 3 (11%) patients in the naproxen-treated
      group. One year after the operation, 4 (17%) patients in the naproxen-treated
      group and 12 (52%) in the control group had heterotopic ossification (p < 0.05).
      Severe ossification developed in 3 patients in the control group and in none in
      the naproxen-treated group. The authors conclude that naproxen given for 1 week
      can decrease the incidence of heterotopic ossification after total hip
      arthroplasty.

PMID- 7634632
TI  - Acetabular reconstruction using bipolar endoprosthesis and bone grafting in
      patients with severe bone deficiency.
AB  - Eighty-one patients who had hip reconstruction with bone grafting and bipolar
      endoprosthesis for severe acetabular deficiency were reviewed retrospectively at
      3 to 8 years postoperatively. Failed total hip arthroplasty was the most common
      indication for operation. Bone grafts were fixed bone blocks, morselized
      cancellous bone, and wafer-type grafts used singly or in combination. The average
      Harris hip rating score was 49.9 points preoperatively, 81.4 points at 1 year,
      and 70.8 points at latest followup examination. The 35 unsuccessful procedures
      included 25 reoperations for implant removal (resection arthroplasty or revision)
      and 10 cases pending revision. At latest followup examination, 54.7% of patients
      considered themselves improved and 62.7% had no or mild pain. Eighty-five percent
      of cases had radiographic evidence of component migration that was superior and
      medial in direction. Overall probability of implant survival was 96% at 1 year,
      but only 47% at 6.5 years postoperatively. Because of the high failure rate, this
      procedure has a limited role in hip reconstruction, but may be a reasonable part
      of a staged reconstruction for patients with massive bone loss or in certain
      revision cases where instability is a concern.

PMID- 7634633
TI  - Second look arthroscopy after meniscal repair. Factors affecting the healing
      rate.
AB  - Second look arthroscopy was performed on 46 of 137 consecutive patients who
      underwent arthroscopic meniscal repair. All tears were of the vertical type.
      Thirty-two tears were located in avascularized areas. Thirty-one patients had
      associated anterior cruciate ligament insufficiencies. Anterior cruciate ligament
      reconstructions were performed simultaneously on 26 patients. The double-needle
      cannula method was used in all the patients. An additional transplantation of a
      vascularized synovial pedicle flap to the suture site was performed on 7 tears in
      avascularized areas. Second look arthroscopy showed no healing in 8 patients and
      healing in 38. Four of the 8 unhealed tears were located in avascularized areas,
      and 4 had unreconstructed anterior cruciate ligament injuries respectively. All 7
      patients with synovial pedicle flaps showed healing. All patients with anterior
      cruciate ligament reconstructions showed healing, and the healing rate was
      significantly higher than that of the other patients (p < 0.005). Patients with
      anterior cruciate ligament insufficiencies showed a significantly lower healing
      rate than the others (p < 0.005). In patients with tears in avascularized areas,
      the conventional meniscal repairs showed a lower healing rate than did the
      repairs with a synovial pedicle transplantation or an anterior cruciate ligament
      reconstruction (p < 0.005). These results suggest that the most important factors
      influencing meniscal healing are the presence of anterior cruciate ligament
      tears, ligamentous reconstruction, and vascularity of the tear site.

PMID- 7634634
TI  - Degloving injuries of the hand and fingers.
AB  - Wound coverage after a complete degloving injury of the hand and fingers is 1 of
      the most difficult problems in hand surgery. Important structures such as
      tendons, nerves, and bones are exposed and will necrose if not covered
      adequately. The goal of treatment should be coverage with a pliable, sensitive,
      and cosmetically similar tissue that will allow early mobilization. The authors'
      experience has led them to adopt the following general guidelines: replantation
      of the avulsed structures whenever possible; early transfer of a free composite
      flap from the foot for a complete and irreparable degloving injury of the thumb;
      and selection of the radial forearm flap for multiple finger lesions. Between
      1981 and 1993, 13 patients were treated for degloving injuries of the hand and
      fingers. Revascularization of the avulsed structures was possible in only 4
      patients. In 6 patients with degloving injuries of the thumb in whom replantation
      was not possible, the thumb was reconstructed using a free wraparound flap from
      the big toe. In 3 patients with degloving injuries of the fingers, coverage was
      obtained as an emergency measure using an island radial forearm flap. In
      conclusion, replantation should be attempted when the degloved skin is available
      and the vessels are not damaged; secondary reconstruction should be done as early
      as possible to limit the time of tendon, bone, and joint exposure.

PMID- 7634635
TI  - Meniscal detachment to approach lateral tibial plateau fractures.
AB  - This retrospective study evaluated 18 patients in whom an extensile approach to
      the lateral tibial plateau involving anterior detachment and retraction of the
      lateral meniscus was used to improve visualization of the tibial articular
      surface. All patients in this study had a significantly comminuted tibial plateau
      fracture with a minimum articular depression of 10 mm. Four of the 18 patients
      had peripheral meniscal tears that were repaired at the time of tibial fixation.
      All patients had a minimum followup of 13 months. The average range of motion was
      0 degrees to 117 degrees. None of the patients had evidence of meniscal symptoms.
      Functional evaluation revealed that 13 of the patients had an excellent result, 5
      had a good result, and 1 a poor result. Five patients evaluated with arthroscopy
      showed complete healing of the anteromedial detachment site of the meniscus. Two
      of the 5 patients also had a meniscal repair that healed. For patients in whom
      there is significant comminution and depression of the lateral tibial plateau,
      this is a safe and effective method of treatment that provides excellent exposure
      of the articular surface to allow an accurate reduction.

PMID- 7634636
TI  - Correction of foot deformity by the Ilizarov method in a patient with Segawa
      disease.
AB  - Hereditary progressive dystonia, or Segawa disease, is rare. Diagnosis depends on
      typical clinical features with normal laboratory findings. It responds well to
      levodopa treatment. This article contains a case report of a patient with Segawa
      disease with a fixed equinovarus foot. A 21-year-old woman was diagnosed with
      Segawa disease since she was 8 years old; she became wheelchair dependent at the
      age of 15. The dystonia responded well to levodopa, except for the fixed-foot
      deformity. The deformity was corrected successfully by the Ilizarov method. The
      patient returned to independent ambulation after surgery. Because similar types
      of foot deformities appeared in several progressive degenerative neurologic
      diseases, the treatable Segawa disease should be added to the list of
      differential diagnoses of progressive degenerative neurological diseases with
      talipes equinovarus.

PMID- 7634637
TI  - Reconstruction using the saddle prosthesis following excision of primary and
      metastatic periacetabular tumors.
AB  - From 1988 to 1991, 17 patients with malignant periacetabular tumors underwent
      limb-sparing surgery and reconstruction using the saddle prosthesis. There were 8
      patients with primary malignant lesions (Group 1), and 9 patients with metastatic
      or systemic tumor involving the periacetabular pelvis (Group 2). All resections
      included excision of the acetabulum. Patients ranged in age from 24 to 76 years
      (average, 59.8 years). Local control was achieved in all patients. Wide margins
      were obtained in all patients with primary pelvic tumors. Functional outcomes
      were rated as follows excellent (10), good (2), fair (1), and poor (4). Three
      patients, all of whom had pulmonary metastasis before surgery, died within 8
      months of surgery. Of the remaining 14 patients, 5 patients died between 6 and 28
      months after the index procedure. At the end of the followup period, 9 patients
      were still alive (6 in Group 1 and 3 in Group 2), with a followup period ranging
      from 15 to 62 months (average, 33.4 months). The overall results for surviving
      patients were 7 excellent and 2 good results, with no fair or poor results.

PMID- 7634638
TI  - Hip reconstruction for femoral head loss from septic arthritis in children. A
      preliminary report.
AB  - Seven children (8 hips) with Choi's Type IV-B sequelae of septic arthritis of the
      hip underwent an unconventional reconstruction technique using a vascular
      pedicled iliac crest graft to replace the destroyed femoral head and neck. The
      average age at surgery was 3.5 years, and the mean followup 7 years. Graft
      incorporation was observed in all patients; however, severe graft resorption was
      found in 1 hip, and mild resorption in 4 hips. The method of internal fixation of
      the iliac crest graft was not ideal and will require modification. Excellent
      femoral head-neck substitution with graft hypertrophy and remodeling was seen in
      3 hips. In 7 hips (88%), vertical hip stability was achieved and a good range of
      hip motion was maintained. All children adapted very well to the operative
      procedures. At the final followup, the symptoms were those of limb-length
      discrepancy; pain was not a symptom.

PMID- 7634639
TI  - An evaluation of various methods of treatment for Legg-Calve-Perthes disease.
AB  - An analysis of 5 methods of treatment for Legg-Calve-Perthes disease was done on
      124 patients with 141 affected hips. Before treatment, all groups were
      statistically similar concerning initial Mose measurement, age at onset of the
      disease, gender, and Catterall class. Treatments included the Scottish Rite
      orthosis (41 hips), nonweight bearing and exercises (41 hips), Petrie cast (29
      hips), femoral varus osteotomy (15 hips), or Salter osteotomy (15 hips). Hips
      treated by the Scottish Rite orthosis had a significantly worse Mose measurement
      across time interaction (repeated measures analysis of variance, post hoc
      analyses, p < 0.05). For the other 4 treatment methods, there was no
      statistically different change. At followup, the Mose measurements for hips
      treated with the Scottish Rite orthosis were significantly worse than those for
      hips treated by nonweight bearing and exercises, Petrie cast, varus osteotomy, or
      Salter osteotomy (repeated measures analysis of variance, post hoc analyses, p <
      0.05). There was, however, no significant difference in the distribution of hips
      according to the Stulberg et al classification at the last followup.

PMID- 7634640
TI  - The acetabular T-type fracture. A biomechanical evaluation of internal fixation.
AB  - The purpose of this study was to evaluate the stability of different types of
      internal fixation requiring anterior, posterior, or combined surgical approaches
      for the T-type acetabular fracture. Eight specimens were loaded 25 times in a
      cyclic manner to 150 N for each type of fixation construct evaluated. The model
      attempted to range the hip through an arc of motion anticipated in the limited
      activities expected after surgery. Strain gauges were placed on the 3 fracture
      planes of the T-type fracture. These gauges measured displacements. Internal
      fixation consisted of a single anterior column plate, compared with a single
      posterior column plate, compared with simultaneous placement of both anterior
      column and posterior column plates. The differences in displacements measured
      between the 3 types of fixation at each of the 3 fracture sites were not
      statistically significant. In evaluating motion at the anterior fracture line,
      the anterior plate made the largest contribution to stability, although this
      result was not statistically significant. The posterior plate similarly
      contributed most to posterior fracture stability, although again not
      statistically significant. Each of the 3 fixations controlled the inferior
      fracture line motions in a comparable manner.

PMID- 7634641
TI  - Microvascular fibular grafts in skeleton reconstruction.
AB  - Extensive bone defects from any cause require large bone grafts. Such large
      defects usually cannot be repaired by conventional, nonvascularized cancellous
      grafts. Before the advent of  microsurgery, many of these lesions could not be
      cured, and amputation was often the only solution. The bone may be transferred
      alone or in combination with skin or muscle or both. Idiopathic femoral head
      necrosis is 1 of the main indications for free microvascular (fibular) transfer.
      The authors propose a new classification for idiopathic femoral head necrosis. A
      technique that has been used for the past 14 years, on providing mechanical
      support and improved blood supply to the femoral head, is described. The fibula
      is favored for its mechanical properties and its vascular pedicle, and because it
      is easier to harvest.

PMID- 7634642
TI  - The glenohumeral-biceps reflex in the feline.
AB  - The existence of a reflex arc from the anterior aspects of the glenohumeral
      capsule to the long head of the biceps was determined in a feline. A single
      articular branch of the musculocutaneous nerve terminating in the capsule was
      identified and stimulated with 100 microseconds supramaximal pulse train at 10
      pulses per second. It was shown tht stimulation of the musculocutaneous articular
      nerve elicited myoelectric discharge in the biceps muscle. Transection of the
      articular nerve just distal to its emergence from the main trunk of the
      musculocutaneous nerve abolished the myoelectric discharge in the biceps,
      confirming the afferent nature of this articular nerve. The mean (+/- standard
      deviation) time delay from the application of the stimulus to the articular nerve
      to the recording of the corresponding myoelectric discharge in the biceps was 2.7
      (+/- 0.3) milliseconds. The existence of a reflex arc from the capsule to the
      biceps confirms and extends the concept of passive (ligaments) and active
      (muscles) restraints of a joint and the synergy between them toward maintaining
      shoulder stability. If demonstrated in the human, such a reflex may have
      significant implications in modification of surgical procedures and the design of
      new rehabilitation modalities for treatment of shoulder defects.

PMID- 7634643
TI  - Remodeling of articular step-offs. Is osteoarthrosis dependent on defect size?
AB  - One of the major unresolved questions in trauma repair concerns the degree of
      step-off that can be accepted in a joint surface. In answer to this question, a
      new rabbit model of femoral step-off was developed. Osteoarthrotic changes in
      cartilage and bone and the failure of repair responses were seen at 20 weeks in
      the presence of a 3-mm wide sagittal defect displaced 5 mm from the joint surface
      and spanning the anteroposterior extent of the medial femoral condyle. This study
      examined the effects of a similar defect, displaced 2 mm from the joint surface,
      to determine whether the development of osteoarthrosis is dependent on the size
      of the step-off. Defects were created in 18 New Zealand white rabbits. In a
      second group, the medial joint surface was osteotomized, but was not displaced.
      In contrast to th first study, cartilaginous and bony repair resulted in closure
      of the surgical defect and restoration of femoral congruity. Histologic and
      biochemical parameters did not differ significantly between groups. The results
      indicate that cartilage and bone possess the ability to remodel small articular
      step-offs and to restore joint congruity. Furthermore, the combined data suggest
      that the development of osteoarthrosis requires significant articular
      incongruity.

PMID- 7634644
TI  - Free vascularized soft tissue flaps for coverage of the foot and ankle.
AB  - Microsurgical procedures for coverage of foot and ankle defects now are
      undertaken with a better understanding of biomechanical requirements, and concern
      for durability, aesthetics, donor site morbidity, and shoe fit. Well-contoured
      muscle flaps including the latissimus dorsi, rectus abdominis, and gracilis
      muscles frequently are used along with thin cutaneous flaps, especially from the
      lateral arm. When good local options are absent and exposed nerves, tendons, and
      bone, and surgical hardware are present, acute free flaps and delayed primary
      procedures are done frequently with excellent success rates (> 90%). Surgical
      adjuncts and pedorthic devices are used readily to enhance functional outcomes
      and to resolve shoe fitting and tissue breakdown problems. Free tissue transfers
      for foot and ankle coverage defects have reached state-of-the-art status, having
      been refined significantly to resolve many earlier problems.

PMID- 7634645
TI  - Molecular biology of matrix vesicles.
AB  - Matrix vesicles are extracellular 100-nanometer-diameter membrane-invested
      particles selectively located within the matrix of bone, cartilage, and
      predentin. They serve as the initial site of calcification in all skeletal
      tissues. Matrix vesicle biogenesis occurs by polarized budding and pinching off
      of vesicles from specific regions of the outer plasma membrane of chondrocytes,
      osteoblasts, and odontoblasts. Seeding of selected areas of matrix with matrix
      vesicles explains the localized distribution of subsequent zones of
      mineralization. Matrix vesicle biogenesis in the growth plate is linked to the
      chondrocyte cell cycle and reflects a stage in programmed cell death (apoptosis).
      Generation of initial hydroxyapatite mineral crystals occurs within the matrix
      vesicle membrane during Phase 1 of biologic mineralization. Phase 1 is controlled
      by phosphatases (including alkaline phosphatase) and Ca-binding molecules with
      which the matrix vesicles are well endowed. Phase 2 of biologic mineralization
      begins with breakdown of matrix vesicle membranes, exposing preformed
      hydroxyapatite to the extracellular fluid after which mineral crystal
      proliferation is governed by extracellular conditions. Phase 1 and Phase 2 of
      mineralization are under cellular control. Phase 1 is initiated by cells
      generating calcifiable matrix vesicles and releasing them into sites of intended
      calcification. Phase 2 is controlled by cells regulating extracellular ionic
      conditions and matrix composition.

PMID- 7634646
TI  - Ankle pain and swelling in a 30-year-old man.

PMID- 7634647
TI  - While early amputation is not recommended, others may be encouraged to follow
      this course on the basis that amputation is 'inevitable'.

PMID- 7634648
TI  - Molecular biology for the clinician.

PMID- 7634649
TI  - Congenital pseudarthrosis of the tibia. Long-term followup of 29 cases treated by
      microvascular bone transfer.
AB  - The authors show that vascularized fibular transplantation is the safest
      technique to treat congenital pseudarthrosis of the tibia. Results of
      transplantation in 29 patients reveal that the rate and speed of healing were
      superior to those of any other published method, and the final outcome at
      maturity was generally acceptable. In addition, the technique allows secondary
      lengthening procedures to be done. Various factors, such as age at first
      fracture, age at operation, gender, and type of fixation, did not appear to
      influence the outcome significantly.

PMID- 7634650
TI  - Microsurgical technic in repair of the traumatized extremity. 1963.

PMID- 7634651
TI  - Advances in microsurgical reconstruction of the congenitally adactylous hand.
AB  - A series of 18 microsurgical toe transfers for congenitally adactylous hands was
      done from 1983 to 1994. The functional results achieved depended on the approach
      and technical features applied to hand reconstruction in congenital amputations.
      Function was improved significantly by using 3-jointed second toes, including the
      metatarsophalangeal joint, and by performing meticulous intrinsic repair. The use
      of donor arteries changed during the 11-year study period toward the goal of
      perfect revascularization with a minimized ischemic time. Abundant nerve supply
      was found to be important for achieving near normal growth of the transferred
      digit. The results showed improvement in the use of the defective extremities.
      The ability to pinch was restored successfully in 14 of 17 congenitally defective
      extremities. Growth measurements were obtained from 11 transfers at followup,
      which ranged from 1.5 to 6 years (mean, 4 years). Linear growth was observed at
      the phalangeal epiphyses, whereas the metatarsal head epiphyses showed clear
      disturbances in at least 2 patients.

PMID- 7634652
TI  - Open type IIIB and IIIC fractures treated by an orthopaedic microsurgical team.
AB  - An orthopaedic team with an extensive microsurgical background treated 46
      patients with open fractures, 22 Type IIIB and 24 IIIC, of the upper and lower
      extremities during the past 10 years. All 24 patients with Type IIIC fractures
      and 12 with IIIB fractures had associated arterial injuries. In all patients from
      both categories, an effort was made to revascularize the limbs using
      microsurgical techniques and to stabilize the fractures as early as possible. Of
      the Type IIIC fractures, 16 were in the lower extremity and 8 in the upper
      extremity. Of the Type IIIB injuries, 8 were in the lower and 14 in the upper
      extremity. Of the limbs with Type IIIC fractures, 13 (54.2%) were salvaged and 11
      (45.8%) were amputated. The latter was related to the proportionally high number
      of tibial fractures (13 of 24), 8 of which were amputated. None of the patients
      with Type IIIB injuries underwent amputation. These results suggest that limb
      salvage in Type IIIB and, particularly, Type IIIC injuries was associated with
      the application of microsurgical techniques to restore complete (Type IIIC) and
      incomplete (Type IIIB) ischemia. The number of amputations in Type IIIC fractures
      was attributed to the open tibial injuries, which are reported to have an
      amputation rate ranging from 60% to 100%.

PMID- 7634654
TI  - Mechanical properties of peripheral nerves.
AB  - Peripheral nerve trunks are viscoelastic tissues with unique mechanical
      characteristics. Tensile strength, which includes elastic limit and mechanical
      failure, concerns surgeons. This study shows that measurements of the load
      necessary to achieve certain elongations on specimens outside the body do not
      correspond with in situ measurements. The necessary load is influenced by the
      presence or absence of branches and by the amount of fibrosis. Because of
      transverse contraction, elongation beyond a certain limit substantially decreases
      intrafascicular volume, leading to increased intrafascicular pressure. Stress
      relaxation is effective only if the nerve repair site is maintained under
      constant tension. Its beneficial effect disappears after 10 minutes if the
      repaired nerve is returned to a relaxed state. Therefore, tension at the repair
      site should be minimized.

PMID- 7634653
TI  - Osteonecrosis of the femoral head. Hip salvaging with implantation of a
      vascularized fibular graft.
AB  - The authors tried to save the hip joint by implanting a vascularized fibular
      graft, augmented with cancellous bone, into the curetted core of the femoral head
      that was affected by aseptic necrosis. Forty of 66 hips were observed for a
      minimum of 20 months and for as long as 66 months (average, 32 months). Clinical
      assessment according to the cause and severity of the disease was done using the
      Harris Hip Score. Twenty-eight hips (70%) were rated excellent, 7 (17.5%) were
      good, 2 (5%) were fair, and 3 (7.5%) failed and were replaced with an artificial
      joint. Clinically satisfactory results, including good and excellent, were
      obtained in 35 hips (87.5%). Radiographic evaluation showed improved appearance
      of the femoral head core in all 15 patients (37.5%) operated on at a precollapse
      stage of the disease. In 20 hips, the deformity of the femoral head was unchanged
      (50%), 2 (5%) became worse, and 3 (7.5%) failed. The number of hips with improved
      appearance as shown on radiographs and those in which the process was unchanged
      equaled the number of hips with satisfactory clinical results. These data show
      that the procedure can induce new bone formation that fuses with the affected
      subchondral bone, thus preventing the articular surface from collapse. This
      suggests that vascularized fibular grafting is an excellent alternative for hip
      salvaging when treating femoral head osteonecrosis.

PMID- 7634655
TI  - Second toe-to-finger transfer in hand mutilations.
AB  - A series of 68 second toe-to-long finger transfers in 55 patients, including 52
      transfers in 41 patients with mutilating injuries and 16 transfers in 14 patients
      with congenital deformities, was reviewed. Mean followup was 6.7 years. The
      failure rate was 6%, and secondary procedures were done in 18% of the patients.
      In the group with traumatic injuries, mean flexion was 36 degrees, with a mean
      extension lag of 33 degrees. Two-point discrimination was an average of 11 mm.
      Grasp was 47% of that for the normal contralateral side, and pinch was 38%. Of
      the manual workers, 62.5% returned to the same job. Analysis of the congenital
      series was more difficult. Although mobility was not significantly better in
      these patients, discrimination was a mean 5 mm (10 patients were tested). Growth
      plates remained open in 86% of the patients. All patients were able to use their
      finger to pinch.

PMID- 7634656
TI  - Nerve expansion. The optimal answer for the short nerve gap. Behavioral analysis.
AB  - Treatment of the short nerve gap remains a challenge for the reconstructive
      surgeon, but it is a clinical problem that can be addressed by nerve expansion.
      In the present study, the effects of slow nerve expansion on the walking behavior
      of the rat were examined. When expansion was applied on a normal sciatic nerve or
      on a transected nerve at either the proximal or the distal segments, permanent
      30% elongation could be achieved. The recovered function from the expanded nerve
      stumps was compared with such classical methods of nerve reconstruction as nerve
      graft, coaptation under moderate tension, and tensionless repair. The results
      compared favorably between the expanded groups and the time-honored methods of
      nerve repair. Analysis of the behavioral data indicated that any amount of
      expansion affected the functional capabilities of the involved nerve. However,
      expansion of a normal nerve and/or proximal segment of a transected nerve was
      better tolerated than distal segment expansion, which suggests that the presence
      of an axon may have a beneficial effect in minimizing the deforming mechanical
      insult. Slow nerve expansion appears to have a definite role in the microsurgical
      management of the short nerve gap.

PMID- 7634657
TI  - The restoration of elbow flexion with intercostal nerve transfers.
AB  - Seventeen patients with absent elbow flexion secondary to brachial plexus
      avulsion injury underwent intercostal neurotization of the biceps muscle.
      Followup was performed at an average of 5 years. The average age in this series
      was 21.8 years; the mean time interval from injury to the surgical procedure was
      6 months. Eight of the 17 patients (47%) obtained good or excellent results as
      defined by Nagano et al. Five patients had muscle function ratings of M2 but were
      unable to power the elbow against gravity. The overall success rate theoretically
      may be increased by (1) decreasing the time interval from injury to neurotization
      to < 5 months; (2) selecting patients < 50 years of age; and (3) using adjuvant
      surgical procedures after neurotization, including tendon transfers and shoulder
      arthrodesis, which may improve results from good to excellent.

PMID- 7634658
TI  - Nonreamed interlocked intramedullary tibial nailing. One community's experience.
AB  - Forty-nine acute displaced tibial fractures (31 closed, 18 open: 5 Grade I, 7
      Grade II, 4 Grade IIIA, and 2 Grade IIIB) were treated in 1 community with a
      standard operative protocol using a distractor without a fracture table, and an
      unreamed interlocked tibial nail. Forty-six fractures healed (94%). Complications
      included 3 nonunions (6%), 2 deep infections (4%), 9 delayed unions (18%), 4
      angular malunions (8%), 2 rotatory malunions (4%), and 12 interlocking screws
      bent or broke (24%). Twenty-eight patients (57%) required at least 1 additional
      operation to obtain union, most commonly dynamization of a statically locked
      nail. The authors conclude that unreamed tibial nails provide adequate
      stabilization of displaced tibial fractures and can be used in the management of
      most open or closed tibial fractures. However, static locking is required in
      axially unstable fractures. Early dynamization or exchange nailing and bone
      grafting should be considered to hasten union and avoid screw failure. The
      distractor is an excellent adjunctive technique for reduction and alignment of
      tibial shaft fractures during intramedullary nailing.

PMID- 7634659
TI  - Open tibial diaphyseal fractures. Results of unreamed locked intramedullary
      nailing.
AB  - Forty-three high energy open tibial diaphyseal fractures were treated with
      unreamed locked intramedullary nails from 1989 to 1992, and were reviewed at a
      minimum of 1 year from injury. There were 6 Grade I, 2 Grade II, 16 Grade IIIA, 9
      Grade IIIB, and 1 Grade IIIC open fractures. Ninety-eight percent of the
      fractures united in an average time of 6.1 months. However, 47% of the fractures
      required an additional procedure before union. Complications included 49% of
      fractures with malunions, 12% deep infections, 41% locking screw breakages, and
      20% compartment syndromes. These results are similar to those achieved with
      external fixation of open tibial fractures. The unreamed locked intramedullary
      nail has not improved the outcome of open tibial diaphyseal fractures because the
      biologic consequences of the injury are of greater significance than the methods
      or techniques of fracture stabilization.

PMID- 7634660
TI  - Fatigue failure in small diameter tibial nails.
AB  - The prevalence of implant failure in small diameter tibial nails has not been
      well characterized. In a series of 130 tibial fractures stabilized with 8-mm and
      9-mm nails, implant failure occurred in 18 fractures (13.8%): 4 nails (3%) broke
      and 16 (12.3%) screws failed. All nail failures occurred in open, unstable
      fractures with delayed union, and all of the nails that broke were dynamically
      locked during the failure. Of the 130 fractures, 128 (98.5%) eventually united.
      Delayed union, degree of comminution, metaphyseal location, and dynamic locking
      of unstable fractures contribute to hardware failure. Based on these findings,
      dynamization could be used to treat delayed union only in axially stable
      diaphyseal fractures. Exchange nailing is recommended to treat delayed union in
      comminuted or metaphyseal fractures to prevent hardware failure. Bone grafting
      should be performed at 6 to 12 weeks for fractures with > 50% bone loss.

PMID- 7634661
TI  - Mechanical failures of intramedullary tibial nails applied without reaming.
AB  - The clinical mechanical failures of small diameter intramedullary interlocking
      nails were evaluated to determine the relationship of failure modes to the type
      or location of tibial fractures. Methods were developed to duplicate failure
      modes in vitro in standardized tests to simulate the clinical situations. Where
      standard test methods were inadequate, new methods were developed to provide
      quantifiable, reliable methods of evaluating potential clinical performance. The
      modes and rates of mechanical failure in the clinical series were consistent
      among participating centers: (1) In diaphyseal fractures with secondary trauma,
      the intramedullary nail bent at the fracture site where the working length was
      unsupported; (2) failures that occurred several weeks after nailing were the
      result of fatigue fractures of the locking screws, usually at the distal end; and
      (3) nail and screw failures occurred most commonly in proximal and distal tibial
      fractures. The strength of the 8- and 9-mm sizes of Synthes and Russell-Taylor
      nails were comparable.

PMID- 7634663
TI  - Diagnosis and management of infection after tibial intramedullary nailing.
AB  - A series of 20 patients with infection after intramedullary nailing of the tibia
      is discussed. The most common pathogen was Staphylococcus aureus, which was found
      in 14 patients (64%). Eleven nails were originally inserted without reaming, and
      9 were reamed. Treatment protocols were based on the time of onset of infection
      (acute, subacute, and chronic) and the status of bone healing. In eight patients,
      the fractures (6) and nonunions (2) were healed at diagnosis of infection and
      were treated by debridement, nail removal, and antibiotics. Twelve patients had
      fractures (8) and nonunions (4) that were not healed. Four were treated with
      debridement, nail removal, and external fixation, and four with debridement and
      nail retention. The overall success rate for eradicating infection was 90%.
      Infection after unreamed nailing had fewer complications and a higher success
      rate for infection control than did reamed nailing. Risk factors identified in
      this study for infection are previous external fixation, severe open fracture,
      and substance abuse.

PMID- 7634662
TI  - Management strategies for bone loss in tibial shaft fractures.
AB  - Fifty open tibial fractures with circumferential cortical bone loss were
      reviewed. Prospective treatment protocols included fracture stabilization with
      repeated irrigation and debridement followed by wound coverage. Bony
      stabilization was accomplished using external fixators, small diameter unreamed
      interlocking nails, and, in rare instances, plate fixation. Bone graft procedures
      included posterolateral bone graft, elevation of the free flap or direct
      anterolateral grafting, bone transport techniques, and free vascularized fibula
      transfer. Average followup was 18 months (range, 9-40 months). The index graft
      procedure was used in 30 patients (60%) for fracture healing. The rate of union
      was 98%, with an average total treatment time of 42.4 weeks (range, 23-80 weeks).
      Malunion was more likely to develop in patients treated with external fixation
      and posterolateral bone graft (p = 0.007). Intramedullary nails with direct bone
      grafting had shorter times to union and shorter total treatment times. The use of
      free vascular fibular transfers in acute injuries was not successful. Good
      results were obtained with bone transport techniques. Developing a healthy soft
      tissue envelope before reconstruction of these injuries is important. Techniques
      of reconstruction had no correlation to the development of nonunion or infection.
      They were valuable in determining malunion and total treatment time. These data
      confirm that carefully staged reconstruction leads to successful outcomes.

PMID- 7634664
TI  - Skeletal stabilization for tibial fractures associated with acute compartment
      syndrome.
AB  - To determine the possible relationship between outcome and fixation method for
      tibial fractures associated with compartment syndrome, the authors
      retrospectively reviewed the records of 96 patients (average age, 31.8 years)
      with this injury. Seventy-eight patients had multiple injuries (average Injury
      Severity Score, 22.37). There were 68 closed and 28 open fractures, including 3
      gunshot wounds. Compartment syndrome was diagnosed by direct measurement or by
      clinical findings. The attending surgeon selected the type of fixation based on
      fracture pattern and associated injuries. Time to healing for the 96 fractures
      averaged 31.6 weeks. There was no significant difference in healing times between
      open and closed fractures or between methods of treatment. Healing time for
      closed fractures was significantly different from that reported for closed
      fractures not associated with compartment syndrome (30.2 compared with 17.3
      weeks, respectively; open fracture healing times were not significantly different
      (35 compared with 29.3 weeks, respectively). The authors conclude that (1)
      compartment syndrome significantly lengthens the time to healing for closed
      tibial fractures but does not significantly affect the time to healing for open
      tibial fractures; (2) closed tibial fractures with compartment syndrome appear to
      act as open fractures; and (3) the method of fixation does not appear to affect
      time to healing for closed or open fractures associated with compartment
      syndrome.

PMID- 7634665
TI  - Exchange reamed intramedullary nailing for delayed union and nonunion of the
      tibia.
AB  - Twenty-eight tibial fractures, initially treated with nonreamed interlocking
      nails, were exchanged to reamed intramedullary nails to promote union. Initially,
      there were 8 closed fractures with compartment syndromes; 5 Type 2 open
      fractures; 6 Type 3 A injuries; and 6 Type 3B injuries. Exchange nailing was
      performed if followup radiographs did not show callus formation between 3 and 5
      months after injury. Originally, 16 of the 28 nailings were statistically locked.
      Twenty-five of 27 fractures united after exchange nailing. In 2 patients with
      bone loss, additional bone grafting was required. Infection developed in 3
      patients after exchange nailing (11%). Exchange nailing is a useful method to
      promote union of tibial fractures when slow consolidation occurs after initial
      treatment with a nonreamed nail. This method should be combined with autogenous
      bone grafting in patients with bone loss. The procedure is safe and effective in
      closed and minor open fractures; however, caution should be exercised in patients
      with prior Grade 3B open fractures because of the risk of infection.

PMID- 7634666
TI  - The infected nonunion of the tibia.
AB  - Ununited fracture of the tibia complicated by infection is not only a complex
      surgical problem but also a chronic and at times debilitating condition. The
      principle methods used to diagnose and stage posttraumatic tibial osteomyelitis
      are described. Infected nonunions of the tibia are characterized by the extent of
      bony loss and the presence of a functional ipsilateral fibula. Using this tibial
      staging criteria, a series of 37 infected nonunions of the tibia are reviewed.
      Twenty patients were male and 16 were female, with an average age of 33 years.
      The distal third of the tibia was involved in 19 patients, the middle third in
      11, and proximal third in 7. Twenty three of the tibia were infected with > 1
      organism. Thirty were Type 3 (tibial defect of 6 cm or less with a long and
      usable fibula), 4 Type 4 (tibial defect > 6 cm without usable fibula), and 3 Type
      5 (tibial defect > 6 cm without usable fibula). The patients were evaluated at an
      average of 61 months after treatment. Union and eradication of infection were
      achieved in 35 of 37 patients. The results of the Health Impact Analysis suggest
      that the infected nonunion of the tibia represented a chronic and debilitating
      disorder with a lasting impact.

PMID- 7634667
TI  - Results of bone grafting for infected tibial nonunion.
AB  - Thirty-two patients with infected tibial nonunions were treated, including 24 men
      and 8 women whose ages ranged from 21 to 72 years (mean, 40 years). Thirty of 32
      patients had bone defects < 3 cm. Using the Cierney-Mader classification of
      osteomyelitis, 11 of 32 (35%) patients were Stage 4A, and 21 of 32 (65%) patients
      were Stage 4B. All patients had irrigation, debridement, and stabilization using
      an external fixation device. Twenty-seven (84%) patients had muscle transfers.
      The time between initial debridement and muscle transfer ranged from 3 to 24 days
      (mean, 4 days). Bone grafting was performed between 6 weeks and 8 months (mean, 8
      weeks) after soft tissue coverage. Patients received intravenous antibiotics for
      2 to 6 weeks (mean, 6 weeks). Twenty patients received anterior grafting, 10
      received posterolateral grafting, and 2 received both. Followup times ranged from
      12 to 49 months (mean, 28 months). Twenty-nine of the 32 (91%) patients had
      tibial unions between 3 to 10 months (mean, 5.5 months) after bone grafting. The
      3 failed tibias united after posterolateral grafting. Infection was controlled in
      all 32 patients. Autogenous cancellous bone grafting using infection control
      principles is an effective means to treat infected tibial nonunions.

PMID- 7634668
TI  - Vulnerability of the posterior interosseous nerve during proximal radius
      exposures.
AB  - This study describes the anatomy of the posterior interosseous nerve and proposes
      how to protect it during the different approaches to the proximal radius. Based
      on the findings presented here, the choice of the approach and the pitfalls that
      might cause posterior interosseous nerve injury were defined. Three surgical
      approaches were used on 30 cadaveric upper limbs: modified Henry's anterior
      approach, Thompson's posterior approach, and a modified Gordon-Boyd's approach.
      Important anatomic structures were localized, marked, and shown on radiographs.
      Plates and screws were applied through the different approaches to determine the
      relationship of the hardware to the posterior interosseous nerve. Measurements
      were taken between the humeroradial joint, as a reference point, and different
      important anatomic structures. It was concluded that the anterior approach to the
      proximal radius is relatively safe and offers the possibility of proximal and
      distal extension. Caution should be taken while applying screws, however, to
      avoid posterior interosseous nerve injury. The radius is superficial posteriorly,
      and many surgeons favor Thompson's approach for exposure of the proximal radius;
      nonetheless, it carries the risk of posterior interosseous nerve injury with
      exposure of the most proximal portion of the radius. The modified Gordon-Boyd's
      approach offers the advantage of exposing both the radius and the ulna, but
      necessitates excessive muscle stripping.

PMID- 7634669
TI  - Sequential levels of ceftriaxone in intervertebral disc removed as part of
      scoliosis surgery.
AB  - A single intravenous loading dose of 1 g ceftriaxone was injected at different
      intervals before surgery for correction of spinal scoliosis. Serum and
      concomitant disc samples were obtained and assay was performed using high
      pressure liquid chromatography. Data showed that the antibiotic levels in
      intervertebral disc space reached 3.5 mcg/mg, which is above the minimum
      inhibitory concentration for most of the relevant pathogens, as early as 1 hour
      after intravenous administration. These therapeutic levels were maintained for
      more than 5 hours, an accepted period for most spinal surgical procedures.

PMID- 7634670
TI  - Cost effectiveness of intraoperative autotransfusion in total hip arthroplasty
      surgery.
AB  - The purpose of this study was to analyze the cost effectiveness of the cell saver
      in reducing homologous blood transfusion requirements in patients undergoing
      primary total hip arthroplasties. In patients who had predonated autologous
      blood, the addition of the cell saver neither reduced the homologous blood
      requirements nor the percentage of patients exposed to banked blood. In patients
      without predonated autologous blood, the cell saver decreased the percentage of
      patients exposed to banked blood by 40% and decreased the mean homologous
      transfusion requirement from 2.6 to 1.5 units per patient (p < 0.05). The cell
      saver became cost effective when 3 units of blood were salvaged. Because the cell
      saver reclaimed a mean of 453 ml (approximately 2 units), it was not cost
      effective. This analysis is confounded by the risk of exposure to blood borne
      potentially life-threatening pathogens. In patients undergoing elective primary
      hip arthroplasty, the availability of predonated autologous blood obviates the
      need for expensive intraoperative blood salvage techniques. If an adequate volume
      of autologous blood cannot be procured preoperatively, or if the clinician
      suspects excessive intraoperative bleeding, then using the cell saver may be
      justified.

PMID- 7634671
TI  - Hydroxyapatite-coated proximal ingrowth femoral stems. A matched pair control
      study.
AB  - A matched pair study of 2 groups of 42 uncemented total hip replacements were
      compared retrospectively after a minimum 3-year followup. Forty-two hips were
      implanted with a hydroxyapatite coating on the proximal femoral patched porous
      surfaces; 42 hips had patched porous-coated stems without hydroxyapatite. There
      were no clinical differences between the matched groups by any criteria of
      measurement. There was no statistically significant difference between the
      matched groups for femoral stem fixation at all followup intervals. At the 3-year
      followup, 90% of the femoral stems in the hydroxyapatite porous group, and 83% in
      the porous control group achieved stable bony fixation. Hydroxyapatite-coated
      femoral stems demonstrated accelerated bone remodeling characterized by proximal
      cancellous hypertrophy. The percentage of femoral stems exhibiting cancellous
      hypertrophy was significantly greater at all followup intervals. This study did
      not demonstrate any clinical advantage of hydroxyapatite being added to a porous
      coated surface. The radiographic changes of bone remodeling seen with
      hydroxyapatite are not known to improve durability of the hip arthroplasty. This
      study again condemns the use of patched porous-coating and titanium-bearing
      surfaces.

PMID- 7634672
TI  - Early flexion routine. An alternative method of continuous passive motion.
AB  - One hundred knees that underwent primary total knee arthroplasties were divided
      into 2 groups: the first 50 consecutive knees were assigned retrospectively to
      Group I (control), and the following 50 knees were assigned prospectively to
      Group II (early flexion). All procedures were cementless meniscal-bearing total
      knee arthroplasties and were performed by the same surgeon. Maximum early flexion
      (Group II) resulted in decreased length of stay, decreased hospital costs, and
      increased range of motion at 1 year. In light of current government interest in
      hospital cost reduction, this method should be considered as an attractive
      alternative to continuous passive motion.

PMID- 7634673
TI  - Discoid lateral meniscus associated with anomalous insertion of the medial
      meniscus.
AB  - Discoid lateral meniscus in the knee joint is common. From July 1990 through
      September 1992, the authors performed arthroscopy on 534 symptomatic knee joints.
      Seventy-seven knees of 72 patients had discoid lateral meniscus. Of the 77 knees
      treated, 4 (5.5%) had discoid lateral meniscus associated with anomalous
      insertion of the anterior horn of the medial meniscus into the anterior cruciate
      ligament. The discoid lateral meniscus was reshaped in the 4 knees, and followup
      was done from 12 to 24 months (average, 20 months) after surgery. The results
      were satisfactory, except for 1 patient who damaged his knee in a traffic
      accident. The authors concluded that this anatomic variant of the medial meniscus
      was not related to the patients' symptoms, but that reshaping the discoid lateral
      meniscus did relieve their symptoms.

PMID- 7634675
TI  - Congenital pseudarthrosis of the clavicle. Histologic examination for the
      etiology of the disease.
AB  - The etiology of congenital pseudarthrosis of the clavicle remains obscure. The
      authors treated a 5-year-old boy with this rare disease. Clinical history and
      radiographs confirmed the diagnosis. Surgical treatment of resection of the
      pseudarthrosis, autologous bone graft, and internal fixation with a small AO
      plate led to successful bone union. Histologic analysis of the pseudarthrosis
      showed that there were cartilaginous caps on the proximal and distal bony ends.
      The appearance of the cartilaginous caps were equivalent to that of developing
      physes. They were adding new bone to the bony ends, which also was confirmed by
      preoperative tetracycline labeling. These observations support the hypothesis
      that the pseudarthrosis is caused by failure of 2 ossification centers to fuse,
      as was previously proposed by others.

PMID- 7634674
TI  - Fractures of the fifth metatarsal. Analysis of a fracture registry.
AB  - To understand better the natural history of fractures of the fifth metatarsal, a
      fracture registry was established consisting of patients who had acute fractures
      of the fifth metatarsal. The first 100 patients were studied to develop data on
      the natural history of injuries to this bone, and on the results of standard
      treatment for those injuries. In this study, 3 fracture subtypes were identified:
      avulsion, true Jones' fracture, and shaft/neck fracture. Avulsion fractures
      healed without immobilization, usually in 4 weeks. Shaft/neck fractures healed in
      plaster casts with weight bearing as tolerated in 4 to 6 weeks. True Jones'
      fractures required a prolonged time to heal when treated with 8 weeks of
      nonweight bearing and then weight bearing as tolerated in a cast. This method
      was, however, successful in 72% of patients (average time until union, 21.2
      weeks). For the 7 patients in whom conservative treatment failed, surgical
      fixation at an average of 25 weeks after injury reliably achieved bony union in
      half the time required with cast treatment. This low-risk procedure met with
      higher patient satisfaction than prolonged casting.

PMID- 7634676
TI  - Delayed high median neuropathy after supracondylar humeral fracture. A case
      report and review of the literature.
AB  - Compression neuropathy of the median nerve around the elbow is an uncommon yet
      well-recognized clinical entity. Acute compression can occur after trauma to the
      elbow, whereas prolonged compression neuropathy usually involves compression
      under a normal or aberrant anatomic structure. The authors present a case of
      severe median nerve compression neuropathy above the elbow that occurred several
      months after a supracondylar humeral fracture in a previously asymptomatic
      adolescent with aberrant soft tissue anatomy.

PMID- 7634677
TI  - Radiographic analysis of tibial fracture malalignment following intramedullary
      nailing.
AB  - Intramedullary nailing of the tibia was performed on 145 tibiae (137 patients)
      for fracture or nonunion from 1985 to 1992. There were 133 cases available for
      radiographic analysis of postoperative tibial alignment. Of the 133 nailings, 16
      (12%) were malaligned (12 acute fractures and 4 nonunion-malunions). Malalignment
      was defined as 5 degrees angulatory deformity in any plane. Malalignment was seen
      in 58% of proximal third fractures, 7% of middle third fractures, and 8% of
      distal third fractures. Of the malaligned fractures, 83% were either segmental or
      comminuted. Thirteen percent of the reamed tibiae were malaligned as compared
      with 9% of the unreamed tibiae. There was no relationship between nail insertion
      site and degree of angulation. The medial entrance angle averaged 9.5 degrees and
      contributed to a valgus deformity in 4 proximal third tibial fractures. The
      average anterior bow deformity of 5 proximal third fractures was 7 degrees
      (range, 5 degrees-12 degrees). Careful attention to operative technique and
      entrance angle, particularly with proximal third or comminuted fractures, is
      recommended to prevent angular deformity and malunion after tibial nailing.
      Proximal third tibial fractures may require a neutral or slightly lateral
      entrance angle to ensure a more anatomic reduction and centromedullary nail
      orientation to offset the tendency for valgus angulation.

PMID- 7634678
TI  - Metastatic retinoblastoma. Recent progress of interest to orthopaedic surgeons.
AB  - Retinoblastoma is the most common malignant intraocular neoplasm of childhood.
      Distant metastases to bone and bone marrow occur. The authors report on a
      retinoblastoma patient with metastases to the extraaxial skeleton. Implications
      for the orthopaedic surgeon and alternative diagnostic modalities are discussed.
      The case presented here exemplifies the potential role for the orthopaedic
      surgeon in making such a diagnosis in a child previously treated for
      retinoblastoma. Secondary nonocular malignant tumors should be considered in the
      differential diagnosis of patients with a history of retinoblastoma who have a
      painful extremity. Radiation treatment of the primary tumor increases the risk
      for nonocular secondary neoplasms. The structural alterations in the
      retinoblastoma gene in patients with osteosarcomas and the possible role of the
      retinoblastoma gene in the origin of osteosarcomas are also discussed.

PMID- 7634679
TI  - Extraskeletal chondroma with chondroblastic and granuloma-like elements.
AB  - A unique case of extraskeletal chondroma occurring in the right ring finger of a
      51-year-old man is reported. The tumor, measuring 4.0 x 2.2 x 1.5 cm, consisted
      of chondroid, granuloma-like, and chondroblastic cell zones associated with fine
      calcification. Immunohistochemically, most of the tumor cells except for
      multinucleated giant cells were positive for vimentin. Cells positive for S-100
      protein were scattered throughout the tumor, and cells positive for alpha-1
      antichymotrypsin were observed in the chondroblastic cell zone and in the
      granuloma-like area. Ultrastructurally, the chondroblastic cells had a
      characteristic microvillous cell border.

PMID- 7634680
TI  - Biodegradable plate fixation of rabbit femoral shaft osteotomies. A comparative
      study.
AB  - Femoral shaft transverse osteotomies in 58 rabbits were fixed with ultrahigh
      strength poly-L-lactic acid plates made by a drawing technique. Similar
      osteotomies in another 35 rabbits were fixed using stainless steel plates. The
      union rate, the mechanical strength of the united bones, bone mineral content and
      density in the area beneath the plate using dual energy x-ray absorptiometry, and
      the cortical thickness beneath and opposite the plate using a digitizer was
      compared between the poly-L-lactic acid and stainless steel groups after
      postoperative periods of 8, 25, and 40 weeks. The poly-L-lactic acid and
      stainless steel groups showed union rates of 67% (39 of 58) and 80% (28 of 35)
      without displacement, respectively. In the poly-L-lactic acid group, plate
      failure occurred in 14% (8 of 58). The mechanical strength of the specimen was
      restored to a level equal to that on the untreated side by 25 weeks, and cortical
      thickness and bone mineral content and density were maintained almost normal for
      40 weeks in the poly-L-lactic acid group. The stainless steel group showed
      significantly lower mechanical strength and led to osteopenia because of stress
      shielding after 25 weeks.

PMID- 7634682
TI  - Knee pain in a 7-year-old boy.

PMID- 7634681
TI  - In vitro degradation and release characteristics of biodegradable implants
      containing trypsin inhibitor.
AB  - The use of a biodegradable implant system that provides a steady, controlled
      release of drugs or bioactive factors can be an attractive delivery vehicle of
      substances that can enhance repair processes in the musculoskeletal system. The
      present in vitro study examined the degradative characteristics and release
      kinetics of a 50 to 50 polylactic acid/polyglycolic acid implant, used as a
      carrier of trypsin inhibitor, during a 10-week period. Morphological and scanning
      electron microscopic examinations demonstrated that the implant degraded in a
      gradual, extended fashion such that by 10 weeks the implant was completely
      dissolved. It also was shown that the protein was released from the implant in a
      sigmoidal fashion with increased release between 3 and 7 weeks. More than 95% of
      the trypsin inhibitor originally incorporated in the implants was released during
      the 10-week test period. To describe further the degradation process of the
      implant, temporal changes in its molecular weight and surface axial strain were
      determined also. It was shown that in the initial 4 weeks, there was a marked
      decrease in molecular weight of the implants. Axial strain decreased and then
      increased over time, suggesting an initial period of stiffening followed by a
      period of degradative softening.

PMID- 7634683
TI  - Functional and anatomical results after rotator cuff repair.

PMID- 7634685
TI  - The treatment of closed, unstable tibial shaft fractures with unreamed
      interlocking nails.
AB  - Forty-seven closed, unstable tibial shaft fractures were treated with locked
      intramedullary nailing without reaming at the authors' institution. Fifty-three
      percent of the fractures were in polytraumatized patients. Followup was possible
      for 38 (81%) fractures. Thirty-three fractures healed within 6 months (87%). All
      patients had unlimited ambulation without assistive devices, and the ability to
      climb stairs in a normal fashion. Range of motion of the knee, ankle, and
      subtalar joints at final followup was normal, except in those patients who had
      concomitant joint injuries. There were 2 delayed unions (5%) and 3 nonunions
      (8%). Three patients had angular deformities. There were no broken nails in this
      series (0%), but 12 of 80 screws were bent or broken. There was 1 (2.6%)
      superficial infection, and 1 (2.6%) case of osteomyelitis. Interlocked,
      intramedullary nailing inserted in an unreamed manner has become the treatment of
      choice for the closed, unstable tibial shaft fracture in the polytraumatized
      patient in the authors' institution. A high union rate, coupled with a lack of
      compartment syndromes or peroneal palsy, makes this procedure an attractive
      alternative to reamed nailing. This study was not able to prove any superiority
      over reamed nail insertion in closed, isolated, unstable tibial shaft fractures.

PMID- 7634684
TI  - Nonreamed interlocking nailing of closed tibial fractures with severe soft tissue
      injury.
AB  - Closed tibial shaft fractures with severe soft tissue trauma require urgent
      surgical treatment to minimize complications such as soft tissue necrosis,
      infection, compartment syndrome, and nonunion. Although time to union and
      complications are similar to open tibial fractures, these injuries often are
      treated as low energy closed fractures. The method of internal fixation depends
      not only on the fracture pattern, but also on the condition of the soft tissues.
      Unlike plate osteosynthesis, the authors believe that virtually all complex
      closed tibial fractures may be treated with an unreamed tibial nail if proximal
      and distal interlocking is possible. With severe closed soft tissue trauma
      (Grades 2 and 3), an unreamed nail may have biologic and mechanical advantages.
      In a prospective study, 21 closed tibial shaft fractures with severe soft tissue
      trauma (Grades 2 and 3) were treated with an unreamed nail. The mean followup was
      29 months. All fractures healed in an average time of 23 weeks. However, 3
      patients required a bone graft, and in 3 patients the fixation was revised. One
      infection occurred after an exchange reamed nailing. Because of the low infection
      and low nonunion rate, the authors recommend unreamed interlocking tibial nails
      for closed tibial shaft fractures with severe soft tissue trauma.

PMID- 7634686
TI  - Primary treatment of a fracture of the leg bones. 1956.

PMID- 7634687
TI  - Unstable fractures of the tibia treated with a reamed intramedullary interlocking
      nail.
AB  - One hundred thirty-four acute unstable fractures of the tibia were treated with a
      reamed intramedullary nail with locking capabilities. There were 101 closed and
      33 open fractures (20 Grade 1 fractures, 12 Grade 2 fractures, and 1 fracture
      from a gunshot wound). Patients were seen in followup for an average of 16 months
      after nailing. The time to fracture union averaged 28 weeks in closed fractures
      and 39 weeks in open fractures. Delayed union (> 6 months) developed in 14
      fractures (8%): 11 closed (11%) and 3 open (9%) fractures. Eleven of the 14
      delayed unions healed spontaneously, or after dynamization of statistically
      locked nails. Seven fractures (5%) were not healed by 9 months and were
      classified as nonunion (2 closed, 5 open). All fractures required major
      additional procedures to obtain union. Infection developed in 13 fractures (10%).
      In closed fractures, there were 2 superficial (2%) and 3 deep (3%) infections; in
      open fractures there was 1 superficial (3%) and 7 deep (21%) infections. The
      authors conclude that reamed intramedullary nails should be restricted to
      unstable, closed tibial shaft fractures. Its use in open fractures even on a
      delayed basis cannot be recommended because of unacceptably high infection rates.

PMID- 7634688
TI  - Proximal third tibial shaft fractures. Should they be nailed?
AB  - Thirty-two extraarticular fractures of the proximal third of the tibia were
      treated with locked intramedullary nails. There were 10 closed and 22 open
      injuries. Treatment consisted of a reamed nail in each of the 5 closed fractures,
      and an unreamed nail in the remaining 27 fractures. Thirty of the 32 fractures
      eventually healed; however, 9 (28%) underwent exchange nailing and 4 (13%)
      required bone grafting. At final followup, 27 of 32 fractures (84%) had
      angulation of 5 degrees or greater in the frontal or sagittal plane. Nineteen of
      the 32 fractures (59%) had 1 cm or more of displacement at the fracture site. In
      8 fractures (25%), there was loss of fixation, most commonly associated with
      placement of a single proximal locking screw. Fractures of the proximal third of
      the tibial shaft do not appear to respond as favorably to intramedullary nailing
      as do fractures in the distal 2/3 of the tibia. Valgus, apex anterior angulation,
      and residual displacement at the fracture site are common after nailing. Surgical
      errors of a medialized nail entry point and a posteriorly and laterally directed
      nail insertion angle contributed to malalignment. Based on their findings, the
      authors have limited the use of intramedullary nailing for proximal third tibial
      shaft fracture and consider alternate forms of fixation (plate or external
      fixation).

PMID- 7634689
TI  - Indirect reduction and composite fixation of extraarticular proximal tibial
      fractures.
AB  - Forty-one extraarticular comminuted proximal tibial fractures were treated during
      a 7-year period. The fractures were proximal tibial metaphyseal injuries or
      metaphyseal-diaphyseal junction injuries with extension proximally and distally
      but not involving the knee joint. All fractures were treated surgically with open
      reduction and internal fixation using an indirect reduction technique with a
      lateral plate, and a medial substitution external fixator concomitantly. All
      fractures were seen for followup until they healed (average healing time, 12.1
      weeks). The timing of internal fixation was based on the status of the soft
      tissue (average time to surgery, 8.5 days after injury). A temporary spanning
      external fixator was used in 17 (41.5%) fractures to allow for further
      assessment, demarcation, and improvement of the anterior soft tissues. There were
      3 (7%) delayed unions, 1 (2%) malunion, and no nonunions. There were 2 (5%) wound
      infections and 5 (12%) pin track problems. One postsurgical soft tissue problem
      was encountered. Through this technique, reliable healing and alignment were
      achieved in this often difficult fracture pattern, particularly for fractures
      that were difficult or impossible to treat with an intermedullary nail.

PMID- 7634690
TI  - Factors influencing the outcome of closed tibial fractures treated with
      functional bracing.
AB  - One thousand consecutive closed diaphyseal tibial fractures, treated with
      prefabricated functional below-knee braces, were analyzed by statistical methods
      to determine factors predictive of final fracture outcome. Neither the age of the
      patient nor the location of the fracture influenced the speed of healing. In 95%
      of the fractures, the final shortening was < or = 12 mm. The mean final
      shortening was 4.28 mm, compared with mean initial shortening of 4.25 mm. This
      confirmed the authors' long-held hypothesis, that, in general, for closed,
      diaphyseal tibial fractures treated with functional bracing and graduated
      weightbearing ambulation, the final shortening does not increase beyond the
      initial one. Final angulatory deformity in any plane was < or = 6 degrees in 90%
      of patients. The presence of an intact fibula was a relative contraindication for
      functional fracture bracing because angulatory deformity was more likely to
      develop. The incidence of nonunion was 1.1%. The high union rate and low
      morbidity associated with functional bracing of closed tibial fractures suggest
      that the routine use of more expensive surgical treatments is difficult to
      justify. A clear understanding of the rationale of functional bracing, its
      indications and contradictions, and its clinical application protocol are
      essential for the attainment of satisfactory results.

PMID- 7634691
TI  - A sequential protocol for management of severe open tibial fractures.
AB  - Fifty consecutive open fractures of the tibia, including 22 Grade IIIB and 4
      Grade IIIC, were treated using a protocol of debridement, immediate wound
      coverage, and intramedullary nailing. Fasciocutaneous flaps were used extensively
      to cover areas of exposed bone. The severity of the soft tissue injury dictated
      the timing of definitive fixation. Fracture location determined implant selection
      and nailing technique. Patients were observed for an average of 21 months. Ninety
      eight percent of the fractures united < 6 months postoperatively. There was 1
      infection (2%), 2 malunions (4%), and 1 case of partial flap necrosis. Locking
      screws broke in 1 patient (2%); the fracture united with < 5 mm of shortening.
      Immediate postdebridement wound coverage, and intramedullary nailing after
      reconstruction of the soft tissue envelope facilitate fracture healing in these
      complex open injuries. Intramedullary nailing can be performed safely to include
      all grades of open tibial fractures from the proximal to distal metaphysis.

PMID- 7634692
TI  - Osteoporosis and aging. Current update.
AB  - Osteoporosis is 1 of the most prevalent musculoskeletal disorders afflicting the
      elderly population today. Together with a propensity for falls, it can lead to a
      life-threatening condition such as a hip fracture, making prevention a key
      concept. In this article, the pathophysiology of bone loss in the elderly is
      reviewed and current methods for diagnosis and treatment are summarized. In
      recently postmenopausal women with significant bone loss, estrogen therapy is the
      preferred treatment. In the older population, adequate nutrition, calcium
      supplementation, and weightbearing exercise are the mainstays of treatment. With
      the development of newer pharmaceutical agents, eventually it may be possible to
      reduce significantly, and even reverse, bone loss in older postmenopausal women.

PMID- 7634693
TI  - Measurement of acetabular version on the axiolateral radiograph.
AB  - There are 3 definitions of acetabular version: true (anatomic) version, planar
      (radiographic) version, and operative version. Although planar version can be
      measured on standard radiographs, the measurement may be inaccurate when applied
      to metal-backed acetabular components. However, another version angle is depicted
      clearly on an angled, cross-table lateral radiograph of the hip--the axiolateral
      view, and this angle readily distinguishes anteversion from retroversion. If the
      angle of the xray beam is known or is standardized, version measured on the
      axiolateral view can be converted to the other version angles. Nomograms for
      these conversions are presented. In most cases, acetabular version measured on
      the axiolateral radiograph closely approximates planar version.

PMID- 7634694
TI  - Bipolar cup design may lead to osteolysis around the uncemented femoral
      component.
AB  - Thirty-eight patients with a total of 45 primary uncemented bipolar
      hemiarthroplasties with smooth femoral components were observed for an average
      period of 5 years. Clinical results were excellent in 17, good in 15, fair in 10,
      and poor in 3 hips. Radiographs showed stem loosening and bipolar head migration
      in 12 and 2 hips, respectively. Endocortical femoral osteolysis developed in 26
      hips (58%). Eight hips required revision surgery. All the revised hips showed
      circumferential wear of the polyethylene insert rims without substantial wear of
      the bearing surface. Histologic examination of the fibrous membrane around the
      stem showed many polyethylene particles that had been phagocytized by macrophages
      or surrounded by foreign body giant cells. No metal particles were observed at
      this site. The intrinsic functional mechanism of the bipolar endoprosthesis leads
      to persistent cyclic impingement of the stem neck on the rim of the bipolar head,
      producing polyethylene particles and frequent stem loosening by periprosthetic
      osteolysis. Unless this structural problem can be corrected and the durability of
      the prosthesis increased, the bipolar system should not be used for
      hemiarthroplastic surgery.

PMID- 7634695
TI  - Cemented revision of failed total hip arthroplasty. Survivorship analysis.
AB  - A review of 107 total hip arthroplasties performed with acrylic cement in 89
      patients at Columbia-Presbyterian Medical Center by 1 surgeon from 1971 to 1990
      revealed a clinical survivorship of 97% at 5 years and 76% at 10 years. The
      average followup was 7.7 years. Analysis of radiographs revealed a 94% success
      rate at 5 years and 62% at 10 years. A transtrochanteric approach was used in 99%
      of procedures. The 13 definite failures (12.1%) included 8 rerevisions (7.5%) and
      5 failures (4.6%) pending revision. Modified Merle d'Aubigne and Postel
      postoperative scores increased significantly from preoperative values (pain, 2.8
      5.3 points; movement, 3.2-5.2 points; function, 2.6-5.4 points). Bone grafting
      was required in 33% of procedures and did not affect survivorship: 24% of
      procedures required acetabular bone grafts; 4% femoral bone grafts; and 5%
      acetabular and femoral grafts. In 46% of hips, removal of the original well-fixed
      femoral cement and plug was deliberately incomplete. Stems of standard length
      were used for these partially rechannelized femurs because the old distal cement
      column served as a plug for the canal. Old osseointegrated polymethylmethacrylate
      was left behind to bond with the new cement column. Cement fracture, complete
      demarcation, and young age were negatively correlated with survivorship.

PMID- 7634696
TI  - Compression of the common peroneal nerve by a cyst of the lateral meniscus. A
      case report.
AB  - Ganglion cysts that compress the common peroneal nerve frequently arise from the
      proximal tibiofibular joint. In a 60-year-old man, the nerve was compressed by a
      cyst that arose from the lateral meniscus and extended around the posterolateral
      aspect of the fibular neck. The origin and extent of the lesion, which could not
      be determined by clinical examination, was seen through magnetic resonance
      imaging. Cysts arising from the lateral meniscus should be considered in the
      differential diagnosis of compression of the common peroneal nerve.

PMID- 7634697
TI  - Single plane and biplane external fixators for knee arthrodesis.
AB  - Thirty-six knee arthrodeses performed using an external fixator with an average
      followup of 48 months were reviewed retrospectively. A single plane fixator was
      used in 19 cases and a biplane fixator in 17 cases. The reasons for fusion
      included an infected total knee arthroplasty (21 cases), aseptic loosening of a
      total knee arthroplasty (9 cases), posttraumatic osteoarthritis (3 cases), and a
      neuropathic joint, an infected unicondylar knee arthroplasty, and a tuberculous
      joint (1 case each). A fusion was obtained after the initial procedure in 22
      patients (61%). With additional procedures, a fusion was obtained eventually in
      27 patients (75%). The fusion rate decreased with an increasing number of prior
      knee procedures. Single and biplane external fixator designs had similar initial
      fusion rates (single 58%, biplane 65%). Complications included 14 nonunions (5
      fused with additional procedures), 6 pin tract infections, 5 delayed unions, 1
      stress fracture through a pin site, and 1 persistent infection resulting in an
      above-knee amputation. Despite biomechanical advances in external fixator design,
      knee arthrodesis remains difficult to achieve in patients who have had multiple
      previous procedures, a failed total knee arthroplasty, or an infected total knee
      arthroplasty with significant bone loss.

PMID- 7634698
TI  - Partial denervation for persistent neuroma pain after total knee arthroplasty.
AB  - Despite the high percentage of patients who are satisfied completely with the
      results of total knee arthroplasty, there is a small group who remain disabled
      because of persistent neuroma pain. Recently, a better understanding of the
      innervation of the skin and capsule around the human knee joint has provided a
      theoretical basis for denervation in this group of patients. Fifteen patients
      were identified who had persistent or worse knee pain for > 6 months after total
      knee arthroplasty. In each patient, component loosening, malalignment, knee
      instability, and infection had been excluded systematically as a source of pain.
      Pain was evaluated preoperatively with the Knee Society Functional Score
      Questionnaire and a visual analog scale. To be selected for surgery, each patient
      must have had a reduction by 5 points on the visual analogue scale for pain after
      undergoing selective nerve blocks. Postoperative assessment was done by a team
      that did not include the surgeon who did the denervation. The technique for
      selective knee denervation is described in detail. All 15 patients had at least 1
      of the nerves to the knee selectively denervated (45 nerves in 15 patients). All
      patients reported subjective improvement in the immediate postoperative period.
      This improvement was maintained at a mean followup of 12 months (range, 6-16
      months). Selective knee denervation is indicated in the management of intractable
      knee pain of neuroma origin after total knee arthroplasty.

PMID- 7634699
TI  - Chronic Achilles tendinopathy. A survey of surgical and histopathologic findings.
AB  - The surgical findings and the histopathology are reported for 163 patients (134
      males, 29 females; mean age, 38 years; range, 13-72 years; 75% athletes) with
      chronic Achilles tendinopathy. Biopsy specimens from symptomatic (155 cases) and
      nonsymptomatic (90 cases) parts of the tendon and from the paratenon (97 cases)
      were obtained. Surgical reports were reviewed and histopathology was evaluated
      according to a standardized protocol. Eighteen tendons also were analyzed by
      immunofluorescence for fibrinogen, immunoglobulins, and complement. Degenerative
      changes (tendinosis) characterized by abnormal fiber structure, focal
      hypercellularity, and vascular proliferation were noted in 90% of biopsy
      specimens from symptomatic parts of the tendons and, to a lesser degree, in 20%
      from nonsymptomatic parts. Fibrinogen could be identified in most lesion biopsy
      specimens. Partial tendon ruptures were present in 19% of the patients and always
      occurred in areas afflicted with tendinosis. The paratenon was mostly normal or
      revealed only slight changes. Increasing age and male gender were associated with
      more pronounced histopathologic changes. Tendinosis, sometimes complicated by
      partial rupture, appears to be the major lesion in chronic Achilles tendinopathy;
      the paratenon is rarely involved. Important features are a lack of inflammatory
      cells and a poor healing response.

PMID- 7634700
TI  - Dynamic support of the human longitudinal arch. A biomechanical evaluation.
AB  - This study was designed to evaluate the dynamic support provided to the human
      longitudinal arch by the leg muscles active in the stance phase of gait and by
      the plantar aponeurosis. Ten fresh adult cadaveric specimens were mounted in a
      materials testing machine. The tendons of the posterior tibialis, flexor
      digitorum longus, flexor hallucis longus, peroneus longus, peroneus brevis, and
      Achilles tendon were attached to force transducers. Plantar loads of 0, 350 and
      700 N were applied, and the tendons were tensioned individually. The Achilles
      tendon was tensioned an amount equal to the plantar load; the posterior tibialis,
      flexor digitorum longus, flexor hallucis longus, peroneus longus, and peroneus
      brevis were tensioned a fractional amount (depending on the proportion of the
      cross-sectional area to the gastrocsoleus complex). The angular relationships
      between the first metatarsal, navicular, and talus were recorded using a 3
      dimensional movement analysis system. An additional series of measurements was
      obtained by positioning the ankle plantarflexed 10 degrees under a plantar load
      of 350 N. Dorsiflexing the toes with the ankle in a neutral position and loading
      the foot to 350 N and 700 N permitted an evaluation of the effect of the plantar
      aponeurosis. The plantar aponeurosis, via dorsiflexion of the toes, contributed
      the most significant arch support in the sagittal plane with a 3.6 degrees
      increase between the first metatarsal and talus at 350 N and a 2.3 degrees
      increase at 700 N. The posterior tibialis tendon consistently provided arch
      support at plantar loads of 350 N and 700 N. The peroneus longus consistently
      abducted the forefoot in the transverse plane at 350-N and 700-N load levels. The
      study provides further insight into the dynamic supporting and deforming forces
      of the longitudinal arch.

PMID- 7634701
TI  - The use of grommets for flexible hinge toe implants. A case report.
AB  - The postmortem examination of bilateral first metatarsophalangeal flexible hinge
      toe implants in a 66-year-old woman with rheumatoid arthritis is reported. The
      prosthesis had been inserted with grommets in 1 joint and without grommets in the
      other 2.5 years before her death. The implants were removed, and the bone/implant
      interfaces were examined microscopically by hematoxylin eosin stains and an
      electron probe microanalyzer. Surfaces of the implants were examined by scanning
      electron microscopy. Silicone particles within the fibrous tissue at the
      bone/implant interface, and a tear and significant scuffing of the implant
      surface, were detected in the joint without grommets. Such changes were not
      detected in the joint with grommets. These findings suggest that grommets may
      improve implant durability and preventing silicone synovitis.

PMID- 7634702
TI  - Gluteoperineal gangrene and sciatic nerve palsy after umbilical vessel injection.
AB  - Thirteen patients with gluteoperineal necrosis of the skin and subcutaneous
      tissue without muscle involvement associated with palsy of the peroneal branch of
      the sciatic nerve were examined at the authors' institution. This syndrome was a
      complication after umbilical vessel catheterization for injection of medications
      mainly for respiratory distress and apnea. Skin and subcutaneous damaged tissues
      required debridement without sedation or anesthesia. Local antibiotic application
      and ultraviolet rays helped heal the lesions, leaving a star-like scar that did
      not cause cosmetic disfigurement or fistulae formation. For the residual peroneal
      nerve palsy with involvement of peroneal, toe extensor, and anterior tibialis
      musculature, the therapeutic approach initially consisted of physical therapy to
      the involved muscles of the foot. Surgery was required only to correct the
      deformity of the foot secondary to muscular deficits. In this series, the final
      results of the muscles involved secondary to nerve palsy were good in 4 patients,
      fair in 6, and poor in 3. No excellent result was noted.

PMID- 7634703
TI  - Kasabach-Merritt syndrome complicating treatment of a closed femoral fracture.
AB  - The Kasabach-Merritt syndrome of consumptive coagulopathy associated with massive
      hemangiomas is a potentially life-threatening problem in patients who sustain
      long bone fractures of the involved extremities. In this syndrome, platelet
      consumption is caused by their sequestration in the sinusoids and epitheloid
      chambers of large hemangiomas. Secondary fibrinolysis then occurs with resulting
      thrombocytopenia, hypofibrinogenemia, and increased fibrin degradation products
      that can lead to disseminated intravascular coagulation. This can result in
      massive bleeding even after minor trauma. In such patients, operative management
      of long bone fractures, including the placement of cutaneous pins for skeletal
      traction, may be contraindicated; nonoperative management may be necessary.
      Kasabach-Merritt syndrome must be suspected in patients with large hemangiomas
      and associated long bone fractures, and appropriate coagulation studies should be
      obtained before operative management or placement of percutaneous skeletal pins.
      Decreased hematocrit and fibrinogen levels associated with thrombocytopenia and
      prolonged prothrombin time and partial thromboplastin time should alert the
      orthopaedist to the possibility of Kasabach-Merritt syndrome, and prompt
      hematologic consultation should be obtained. If surgical treatment is deemed too
      dangerous because of the possibility of uncontrollable disseminated intravascular
      coagulation, the only prudent option may be a closed reduction and cast
      application after appropriate medical management of coagulation parameters.

PMID- 7634704
TI  - Subcutaneous involvement after a metacarpal chondrosarcoma. Case report and
      review of literature.
AB  - The relatively high probability of local recurrence after excision of
      chondrosarcomas has been attributed to the avascularity of the cartilage tumor
      matrix, making the neoplastic cells less dependent on an extrinsic blood supply.
      This report is of a case of subcutaneous involvement by chondrosarcoma from a
      metacarpal to a site on the ipsilateral forearm several centimeters remote from
      the resection incision in the absence of local recurrence or pulmonary
      metastases. The pertinent literature regarding cutaneous involvement, local
      recurrence, and transplantation of cartilage neoplasms is reviewed.

PMID- 7634705
TI  - Total femoral endoprosthetic reconstruction.
AB  - Twenty-one consecutive total femoral replacements performed at 2 institutions
      were reviewed. The surgical indications varied and included bone loss caused by
      tumor resections (12 patients), failed prior massive partial femoral
      endoprostheses (6 patients, 5 of whom had prior tumor resections), or difficult
      to treat fractures and nonunions (3 patients, 2 of whom had prior
      endoprostheses). Two patients with tumors died within 2 months. The results in
      the 19 longer-term survivors were satisfactory in 16 patients (good in 7, fair in
      9) and poor in 3. Although not commonly used, when this method was indicated it
      provided an option to hip disarticulation, which often was the only other viable
      option. Age was the prime determinant of clinical outcome. Average active hip and
      knee range of motion was better in younger patients (< 60 years old, 66 degrees
      and 81 degrees, respectively) than in older patients (> or = 60 years old, 43
      degrees and 49 degrees, respectively). All household ambulators required walkers
      and had a mean age of 81 years; community ambulators requiring 1 cane had a mean
      age of 46 years; and community ambulators using no walking aids had a mean age of
      22 years.

PMID- 7634706
TI  - Iatrogenic femoral neck fracture in transient osteoporosis of the hip. A case
      report.
AB  - The diagnostic evaluation of suspected cases of transient osteoporosis of the hip
      does not typically include biopsy. Presented herein is a case in which an open
      biopsy procedure was undertaken in the presence of severe osteopenia. An
      iatrogenic fracture occurred during the surgical exposure. The fracture healed
      and the condition subsequently resolved. This complication suggests the
      importance of noninvasive diagnostic modalities in the assessment of this
      condition. The fragility of the proximal femur also suggests a potential role for
      a period of protected weight bearing in the management of transient osteoporosis
      of the hip.

PMID- 7634707
TI  - Supracondylar femoral fractures in the frail elderly. Fractures in need of
      treatment.
AB  - The investigators of this study reviewed 112 consecutive frail elderly patients
      with supracondylar femoral fractures to evaluate primarily functional outcomes to
      optimize initial treatment of these challenging patients. A high 1-year mortality
      rate (22%) and significant decrease in function and quality of life occurred in
      frail elderly patients who sustained supracondylar femoral fractures. No
      statistical relationship could be found among preinjury function, age, cognitive
      function, type of fracture, treatment, and overall results. Nine percent of
      patients required late above-knee amputation in the involved extremity because of
      displacement of the fracture or infection or both. Optimal treatment for this
      type of patient remains elusive. Primary above-knee amputation may be the
      preferred treatment in patients who are this severely affected.

PMID- 7634708
TI  - Delayed diagnosis of a peroneal artery false aneurysm at a concomitant tibial
      fracture. A case report.
AB  - A 49-year-old man had posttraumatic persistent calf swelling and a tibial and
      fibular fracture. Despite the intramedullary nailing of the fracture, the
      swelling did not improve, and at the 6th postoperative week it was misdiagnosed
      (using venogram) as deep vein thrombosis. Therefore, it was mistreated with
      anticoagulants, which led to great deterioration of the local signs. An
      arteriogram revealed an initially missed false peroneal artery aneurysm. Surgical
      treatment was performed immediately. The 6-week delay had led to some atrophy of
      the posterior compartment muscles, fortunately without any permanent disability.
      The importance of proper and early diagnosis of posttraumatic persistent calf
      swelling is stressed.

PMID- 7634709
TI  - The huckstep nail. Stable fixation of mechanically deficient femoral bone.
AB  - A Huckstep intramedullary nail was used to treat 23 fractures in which the femur
      was mechanically deficient due to pathologic fracture, nonunion, or complex
      fracture in osteoporotic bone. All nailings were performed by open surgery, and
      in some cases this was augmented by corticocancellous bone grafting. The Huckstep
      nail allows the use of multiple cross screws at 15-mm intervals, providing
      immediate and adequate stability with successful early postoperative
      weightbearing. The results at followup were good in functional and radiologic
      terms, with no cases of fixation failure or infection. The quality of
      instrumentation allowed the nail and screws to be inserted without difficulty;
      however, the straight profile of the nail may cause problems in the distal femur,
      as seen in 1 patient. The authors conclude that this device offers significant
      mechanical and practical advantages over most other forms of fixation, where
      early weightbearing is desired in the presence of deficient bone. It is not ideal
      for distal femoral fractures, particularly in the presence of excessive femoral
      bowing.

PMID- 7634710
TI  - Obturator internus pyomyositis. A case report.
AB  - Pyomyositis appears to be increasing in prevalence in temperate climates, and
      often the orthopaedist is integral in the decision making and care of these
      patients. This is the first reported case of spontaneous bacterial pyomyositis
      involving the obturator internus muscle. Deep pelvic infections involving the
      psoas, iliacus, piriformis, and obturator internus can be a significant cause of
      morbidity and mortality. The infection subsequently may exit the pelvis, and
      conceivably may progress to a septic hip, bursitis, or lower extremity
      cellulitis. Improvements in noninvasive imaging such as ultrasound, computed
      tomography, and magnetic resonance imaging have produced finer resolution of
      tissue planes. Because of the pathology's deep location within the pelvis of the
      patient described here, all 3 tests were integral in the surgical planning,
      exposure, and proper diagnosis. Although 95% of pyomyositis cases are caused by
      Staphylococcus aureus, cases of pyomyositis with negative cultures have been
      described. Consideration should be made of disseminated Neisseria gonorrhoeae in
      sexually active individuals, and cultures should include Thayer-Martin agar to
      decrease the likelihood of a false-negative culture result.

PMID- 7634711
TI  - Acute hematogenous osteomyelitis of the epiphysis.
AB  - Acute primary infection of the epiphysis is uncommon. This article presents 2
      cases. An acute osteomyelitis of the distal femoral epiphysis, which was not
      diagnosed until 2 weeks after the onset of symptoms, developed in a 4-year-old
      boy. The epiphyseal infection spread into the knee joint, necessitating surgical
      debridement. An acute osteomyelitis of the proximal tibial epiphysis developed in
      a 23-month-old girl. Although the diagnosis was not confirmed until 1 week after
      the onset of symptoms, she responded well to a course of intravenous antibiotics
      followed by oral antibiotics. The epiphysis is a potential site for acute
      hematogenous osteomyelitis. Prompt diagnosis and early treatment may prevent
      spread of the infection into the adjacent joint.

PMID- 7634712
TI  - Corticosteroid enhances the experimental induction of osteonecrosis in rabbits
      with Shwartzman reaction.
AB  - Bacterial endotoxic reactions can cause osteonecrosis in humans by disseminated
      intravascular coagulation. The authors first used a combination of the Shwartzman
      reaction and corticoid injections in rabbits to develop a new animal model of
      osteonecrosis. This model showed a significantly higher incidence and wider area
      of osteonecrosis in the femur and humerus than that found in rabbits with either
      Shwartzman reaction or steroid injection alone. Osteonecrosis was observed in
      several foci that were distributed from the diaphysis to the epiphysis in both
      bones. Histologically, the bone marrow cells underwent necrosis, whereas the bone
      trabeculae demonstrated either empty lacunae or pycnotic nuclei of osteocytes.
      Exogenous steroids appeared to potentiate the Shwartzman reaction and the
      magnitude of osteonecrosis, perhaps by increasing endothelial damage and
      hypercoagulability of those intraosseous and extraosseous vessels that
      subsequently thrombosed. This model may not only be useful in clarifying the
      etiology and early pathogenesis of human osteonecrosis after corticoid therapy,
      but also in designing pharmaceuticals for prevention and early treatment.

PMID- 7634713
TI  - Freezing influences the healing of rabbit medial collateral ligament autografts.
AB  - Connective tissue allografts are treated commonly with deep freezing to
      facilitate their storage in tissue banks and to reduce their immunogenicity. The
      influence of freezing on the healing of these grafts is unknown. The effect of an
      aggressive freezing protocol on ligament graft healing in a nonimmunogenic
      autograft model was investigated. The femoral-medial collateral ligament-tibial
      complex of the rabbit knee was transplanted orthotopically into the site from
      which it had just been harvested. The fresh group had their grafts rinsed in
      normal saline, and the frozen-thawed group had their grafts repetitively frozen
      thawed in liquid nitrogen immediately before reimplantation. The healing of the
      ligament complexes were evaluated mechanically at intervals as long as 1 year
      after transplantation. Repeated freezing had little effect on the initial
      mechanical behavior of the graft complexes but was found to be detrimental to
      subsequent graft incorporation. The frozen-thawed grafts were weaker than the
      fresh grafts overall, and this effect persisted over time. The failure load and
      stress of the frozen-thawed grafts reached only 87% and 75% of that of the fresh
      grafts after 48 weeks. Because the initial mechanical effects of freezing were
      minimal, subsequent effects on graft healing must be attributed to factors other
      than gross structural injury. Despite showing almost no signs of damage to bone
      ligament-bone grafts initially, freezing procedures may have important subsequent
      biologic consequences that may influence the clinical success of stored
      connective tissue grafts used in ligament reconstruction.

PMID- 7634714
TI  - Outcome and long-term results following total hip replacement in elderly
      patients.
AB  - The authors reviewed the preoperative and postoperative charts and radiographs of
      100 patients who were at least 80 years old when they underwent total hip
      arthroplasty. Seventy-six of these patients were available for further
      reexamination and evaluation. The average patient age was 85.2 years old (range,
      80-97 years). The average followup period was 59.4 months (range, 26-146 months).
      The female to male ratio was 4 to 1. Osteoarthritis was the most common
      diagnosis. Hospital stay ranged from 12 to 39 days. Preoperative Charnley pain
      and walking scores averaged 5.1 points of a possible 12 points, and postoperative
      scores averaged 10.6 points. Eighty-eight percent of patients remained community
      walkers, and 60% used a cane. Four percent of the patients had 1 dislocation.
      There were no instances of mechanical loosening and no deaths. Subjective
      satisfaction was high. The level of independent living was maintained in 96% of
      patients at long-term followup. A satisfactory and cost-effective health outcome
      can be anticipated after total hip arthroplasty in octogenarian and nonagenarian
      patients.

PMID- 7634715
TI  - Biomechanical properties of hip cartilage in experimental animal models.
AB  - The material properties of normal adult articular cartilage were determined in
      the femoral head and acetabulum of baboons, dogs, and bovines, and were compared
      with those of normal human hip cartilage. In situ creep and recovery indentation
      experiments were performed using an automated creep indentation apparatus. To
      curvefit the entire creep curve, a numerical algorithm based on biphasic finite
      element methods and nonlinear optimization was developed. This effort represents
      the first successful use of 100% of the creep indentation curve to obtain the
      mechanical properties of normal articular cartilage. The results show that
      material properties of articular cartilage exhibit significant topographical
      variations in the femoral head and acetabulum, and between these two bone
      structures. Furthermore, significant differences exist in the mechanical
      properties of hip cartilage among the 4 species. Specifically, in all species the
      smallest aggregate modulus is found in the inferior aspect of the femoral head.
      Among all species, human hip cartilage is the stiffest in all test sites; bovine
      tissue is the softest. Human tissue has the smallest Poisson's ratio and
      permeability in all test sites. The aggregate modulus of human hip cartilage is
      closely resembled by that of baboon hip cartilage. Anatomically, canine and
      baboon hips exhibit similar characteristics to the human hip joint; the bovine
      hip joint is distinctly different. Based on this study's data, the baboon
      represents the most appropriate animal model of normal human hip articular
      cartilage.

PMID- 7634716
TI  - Sensitivity of osteoinductive activity of demineralized and defatted rat femur to
      temperature and duration of heating.
AB  - For autogenous and allogeneic bone grafts, heat treatment has been thought to
      kill malignant cells and viruses such as human immunodeficiency virus. It is
      unclear whether heat treatment could preserve bone-inductive activity. Cortical
      bones from 6-week-old rat femurs were heated in a water bath at a temperature of
      50 degrees-100 degrees C for periods of 15 minutes to 10 hours. After treatment,
      they were defatted and decalcified. Each sample was transplanted into the
      hamstring muscle of 3-week-old rats. Eleven days after transplantation, the
      samples were removed and messenger ribonucleic acids (mRNAs) were determined for
      alkaline phosphatase and collagens in the transplant. Twenty-one days after
      transplantation, actual bone formation was studied by histologic analysis and
      measurement of calcium content. Heat treatment at 60 degrees C for 10 hours and
      at 70 degrees C for 1 hour preserved bone-inductive activity, as indicated by the
      induction of mRNAs for alkaline phosphatase and Type I and Type II collagens.
      Significant decreased in Type II collagen mRNA and calcium content were observed
      at 70 degrees C when the transplants were heated for 10 hours, suggesting the
      importance of evaluating the duration of heat treatment.

PMID- 7634717
TI  - Arthroscopic management of the acromioclavicular joint disorder. A review.
AB  - Acromioclavicular joint symptoms may originate from either osteolysis or
      osteoarthritis. Initial treatment consists of 6 to 12 months of physical therapy,
      nonsteroidal antiinflammatory drugs, avoidance of exacerbating activities, and
      other conservative modalities. The majority of patients respond well, but a few
      remain unable to return to their previous or desired activity levels. Previously
      this group of patients underwent open resection of the distal clavicle. [The
      approach violates the deltotrapezial fascia, weakening the surgically treated
      extremity, which has caused controversy in the literature.] Even without
      complications, the recovery and time away from work is prolonged. With advances
      in arthroscopic techniques, resection of the distal clavicle and medial aspect of
      the acromion has become possible with minimal invasiveness. The arthroscopic
      technique offers the advantages of rapid rehabilitation with excellent functional
      results. Several different modifications of 2 basic approaches, the bursal and
      direct superior, have been described by various authors. The authors sought to
      examine critically and review the data supporting the choice of arthroscopic
      surgery rather than an open technique, as well as the advantages of 1
      arthroscopic approach over the other.

PMID- 7634718
TI  - Knee pain in a 34-year-old woman.

PMID- 7634719
TI  - A case of acromioclavicular dislocation with epiphyseal separation of the
      coracoid process.

PMID- 7634720
TI  - Deep venous thrombosis is the most common complication after hip surgery.

PMID- 7634721
TI  - The effect of aging on the shape of the proximal femur.
AB  - The design of cementless femoral prostheses is based on the assumption that age
      and gender do not affect the shape of the proximal femur. To test this
      hypothesis, standard anteroposterior and lateral radiographs were prepared of 4
      sets of 20 femora, obtained from young (range, 40-60 years) and elderly (range,
      60-90 years) donors of both genders. The intracortical and extracortical borders
      of each femur were digitized electronically, and key parameters were measured to
      define the shape and dimensions of the medullary canal and the position of the
      femoral head. Systematic differences were observed between the size and shape of
      male and female femora. Extracortical dimensions were larger in the male femora
      by 14% to 19%, and endosteal dimensions by 11% to 24%. However, there were no
      significant differences between the canal shape of young male and young female
      femora in the coronal, sagittal, or transverse planes. The male femora displayed
      no significant differences in canal shape or endosteal width as a function of
      age. Profound differences were observed in the endosteal shape and diaphyseal
      dimensions of the young and old female femora. The older female femora had wider
      canals at the level of the isthmus, with a significant reduction in the canal
      flare index (the ratio between the canal width proximal to the lesser trochanter
      and at the isthmus). This study demonstrates that cementless femoral prostheses
      of 1 standard shape cannot provide a close fit to the endosteal contours of young
      and elderly women.

PMID- 7634722
TI  - Total knee arthroplasty in the very aged.
AB  - Twenty-six total knee arthroplasties were performed on 20 patients who were 85
      years or older (mean, 87 years). Only those patients with a minimum of 3 years'
      followup are reported here. One patient died approximately 1 year after surgery,
      and 4 patients (5 knees) were lost to followup, leaving 20 total knee
      arthroplasties in 15 patients to be reported. Postoperative results were based on
      a 100-point scoring system that is a modification of the Knee Society scoring
      system. Eleven knees received an excellent rating, 4 good, 2 fair, and 3 poor.
      The primary indication for surgery in this patient population was pain control.
      Most patients required the continued use of ambulatory assistive devices such as
      a cane after surgery, but pain relief was good or excellent in 19 of 20 knees and
      quality of life improved. All patients tolerated the procedure well, with few
      postoperative complications noted. There was no perioperative mortality, and all
      wounds healed normally. Total knee arthroplasty is a safe and reliable procedure
      in the very aged patient for management of pain and deformity secondary to
      arthritis of the knee.

PMID- 7634723
TI  - The physiology of the aging process in the musculoskeletal apparatus. 1955.

PMID- 7634724
TI  - Arthroscopic surgery of the knee in the geriatric patient.
AB  - There remains some controversy and confusion regarding arthroscopic surgery of
      the knee in the elderly population, particularly for patients with
      osteoarthritis. A retrospective review was undertaken of 105 knees in patients 60
      years or older who had arthroscopy during a 4-year period. The surgical outcomes
      were evaluated using a postoperative knee scoring system at a mean followup
      period of 11.7 months. Good and excellent results were obtained in 65% of knees.
      The most significant predictors of good outcome were preoperative mechanical
      symptoms, such as those resulting from loose bodies or flap tears of the
      meniscus, and only mild articular degeneration seen at arthroscopy. A review of
      the literature reflects similar success rates. Although the results are equivocal
      by orthopaedic standards, in selected patients arthroscopic surgery can offer
      significant relief of acute symptoms and defer more extensive surgical procedures
      with minimal risk.

PMID- 7634726
TI  - Decision making in upper extremity problems in the elderly.
AB  - As life expectancy continues to increase, orthopaedists must become more
      knowledgeable about upper extremity problems common to geriatric patients.
      Alternatives to direct repair of certain soft tissue injuries must be considered,
      because of their diminished healing ability and the morbidity associated with
      prolonged immobilization. Osteoporosis present in these patients affects surgical
      management of difficult fractures. Acquired soft tissue disorders such as nerve
      compression and Dupuytren's contractures often will require operative
      intervention to improve hand function. Osteoarthritis and rheumatoid arthritis
      disproportionately affect this age group. A variety of conservative and operative
      treatments are available to improve quality of life in these patients.

PMID- 7634725
TI  - Foot problems in the geriatric patient.
AB  - Foot disorders are 1 of the most common problems of the elderly population. Most
      of these disorders are acquired and can be managed easily with shoe modifications
      and pads. Surgery should be reserved for those with severe fixed deformities.
      Determination of adequate arterial supply is mandatory before beginning any
      surgical correction. In most cases, the simplest procedure leads to the best
      result to avoid prolonged immobilization and wound problems.

PMID- 7634727
TI  - Spinal disease in the aged.
AB  - Treatment of the diseased spine in the elderly is a difficult challenge for the
      practitioner. Spinal surgery for this population requires specialized surgical
      skills. Patient evaluation, nonoperative treatment, surgical indications,
      surgical techniques, and postoperative management involve unique considerations.
      The patient's functional expectations, general medical condition, and proposed
      benefits from surgery must be addressed before any surgical intervention. Spinal
      surgery for the aged requires the orthopaedic surgeon to consider this patient as
      more than just an older individual and demands that the entire perioperative
      milieu be examined and its issues resolved. The projected data on aging of the
      United States population make this issue increasingly important.

PMID- 7634728
TI  - Rehabilitation of the geriatric orthopaedic patient.
AB  - Older patients who are referred for rehabilitation after undergoing orthopaedic
      procedures have numerous age-related conditions that may interfere with physical
      performance and safety. The general rehabilitation goals are to return each
      patient to the premorbid functional level of mobility and self-care, teach the
      exercises that are to be performed after hospital discharge, reduce the risk of
      falls, and ensure that the patient is discharged to a safe environment. Before
      elective surgery, the elderly orthopaedic patient should be instructed to perform
      breathing exercises to prevent pulmonary complications and active lower limb
      exercises to maintain good circulation and joint mobility, and be instructed in
      functional activities for mobilization in and out of bed. Postoperatively, the
      interdisciplinary rehabilitation team must facilitate early resumption of active
      exercises and self-care tasks and discourage prolonged bed rest and dependency on
      nursing staff and family members. Physical and occupational therapy should be
      provided to restore mobility and self-care functions. If discharge to home is
      planned, the home environment should be assessed and modifications recommended to
      reduce the risk of falls and ensure independent functioning to the extent
      possible. When the rehabilitation goals have been obtained, the patient should be
      discharged from the hospital, but additional therapy may be required, either at
      home or at an outpatient facility.

PMID- 7634729
TI  - Ethical aspects of care of the geriatric orthopaedic patient.
AB  - Ethical aspects of care of the geriatric orthopaedic patient include respecting
      patient self-determination as the primary standard of decision making; using
      advance directives or appropriate surrogate decision makers when patient
      decisional capacity is lost; and balancing the benefits and burdens of any
      intervention and its alternatives in arriving at a treatment decision. With an
      increase in managed care plans, questions of justice in care of the elderly will
      be raised. Physicians face fiscal incentives that encourage fewer surgical
      procedures and lower levels of health care particularly in the elderly, a group
      that notably has benefited from the functional enhancement permitted by modern
      orthopaedic techniques. Professional vigilance is required of physicians to
      ensure that appropriate health care services continue to be available to
      patients.

PMID- 7634730
TI  - Cortisone injection with anesthetic additives for radial epicondylalgia (tennis
      elbow).
AB  - In a prospective, randomized, double-blind study of radial epicondylalgia (tennis
      elbow), 109 patients with an average symptom duration of 8 months were considered
      for treatment with a single 1-mL injection of the steroid triamcinolone combined
      with either lidocaine or bupivacaine. The patients received clinical examinations
      at regular intervals for 1 year, and followup included visual analog pain scale
      and questionnaires. The 2 groups were comparable and for many factors distributed
      completely evenly with respect to gender, age, symptom duration, side dominance,
      type of pain onset, earlier treatment, and occupational loading. The only
      difference between the groups receiving lidocaine or bupivacaine was found at 2
      weeks, when the bupivacaine additive yielded a better outcome for patients who
      had not been treated in any way before, for those with a short history of
      epicondylalgia, or both. The steroid injection treatment, regardless of which
      local anesthetic was given, presented a typical pattern, with symptoms relieved
      quickly by 2 weeks and then deterioration for many patients at 3 months,
      indicating a tendency to recurrence. A considerable loss of patients to other
      treatments at the 1-year followup indicated an equivocal long-term result.
      Patients who had not been treated earlier in any way had a more favorable
      prognosis, as did those with a history of epicondylalgia to 3 months.

PMID- 7634731
TI  - Surgery of the midface and nasolabial fold. Introduction.

PMID- 7634732
TI  - An historical glimpse of the evolution of rhytidectomy.
AB  - Obviously there is much more to be written about the facelift operation than this
      very brief history. Although it was not intended to be definitive in character,
      its modest intention was to provide the reader with some of the evolution of the
      operation and to describe clinical and cadaveric work done over the last two
      decades as it relates to the aging midface.

PMID- 7634733
TI  - Changes of the midface with age.
AB  - To understand how to re-create the youthful look, one must understand which
      tissues change with age, the direction of that change, and the amount of that
      change. This article discusses the subjective and objective results of a study of
      the evolution of the midface with aging.

PMID- 7634734
TI  - Anatomy of the midface.
AB  - Surgical procedures for the midface and nasolabial fold demand that the surgeon
      possess a magnified knowledge of the facial anatomy and its structural
      relationships. With this knowledge, the surgeon limits complications while
      achieving better results. This article reviews the anatomy of the midfacial
      subcutaneous soft tissues.

PMID- 7634735
TI  - Surgical anatomy of the facial nerve.
AB  - (1) The temporal branch of the facial nerve emerges within the parotid gland to
      cross the zygomatic arch at the deep surface of the temporoparietal fascia. The
      nerve is separated from the deep temporal fascia immediately above the zygomatic
      arch by a loose areolar plane; this plane may be obliterated when previous
      surgical procedures have been performed in this region. (2) The temporal branch
      can be found within a trajectory that has been described relating the lower
      portion of the auricle to the lateral aspect of the eyebrow. However, one must be
      aware that these surface landmarks may vary with respect to the underlying
      skeleton and from one individual to the next. (3) Recent studies indicate that
      the temporal branch consists of not one, but multiple rami that cross the
      zygomatic arch. Because there are multiple rami to the temporal branch of the
      facial nerve, any single trajectory can describe only a portion and not the
      entirety of the temporal branch. (4) The zygomatic, buccal, and marginal
      mandibular branches of the facial nerve innervate the mimetic muscles of the face
      from either their superficial or deep surfaces. Several mimetic muscles are
      innervated by two or more branches of the facial nerve. (5) Interconnections
      between the zygomatic and buccal branches are noted in over 70% of cases, whereas
      interconnections between the temporal or marginal mandibular branches to other
      facial nerve branches occur in less than 15% of cases. (6) The zygomatic, buccal,
      and marginal mandibular branches lie in intimate relationship with the retaining
      ligaments of the face. Surgical dissection for release of the zygomatic ligament,
      the masseteric cutaneous ligament, or the mandibular ligament should be performed
      meticulously and with extreme caution.

PMID- 7634736
TI  - The armamentarium to battle the recalcitrant nasolabial fold.
AB  - The nasolabial fold is the consequence of thinning of the skin, ptosis or
      deposition of fat laterally, and presence of excess skin. The ideal procedure for
      combatting this defiant and undesirable aging change would be to eliminate the
      excess skin, add to the thickness of the skin under the crease, and shield the
      bands from adherence to the dermis, with or without repositioning or resection of
      the fat laterally. However, under particular conditions, the patient or physician
      may choose alternative techniques. These include injection of fat, addition of
      fat graft, or direct excision. Patients with extremely thin skin are better
      candidates for direct excision, whereas those with thicker skin may more suitably
      benefit from fat injection or fat graft.

PMID- 7634737
TI  - Strategies for nasolabial levitation.
AB  - A facelift strategy that has proved useful follows certain steps: (1) incision
      lines and excision lines are drawn preoperatively with the patient seated,
      providing a pattern for skin excision. (2) The skin/soft-tissue flap is elevated
      from the surface of the SMAS, platysma, and frontalis (SMA plane). (3) The
      retaining ligaments of the cheek are released. (4) The zygomaticus major muscle
      is plicated. (5) Advancement of the zygomatic ligament is emulated by sutures
      from the modiolar retinacular tissue to the zygomatic periosteum/masseteric
      aponeurosis. (6) Closure of the patterned skin excision takes up the intrinsic
      nasolabial redundancy and also the nasolabial redundancy resulting from steps 4
      and 5.

PMID- 7634738
TI  - Elevation of the malar fat pad superficial to the orbicularis oculi muscle for
      correction of prominent nasolabial folds.
AB  - The technique of elevation of the midface malar fat pad for correction of
      prominent nasolabial folds is described as part of the multiple vector facelift
      operation. Facial anatomy of aging, indications for operation, patient selection,
      postoperative follow-up, and complications are reviewed. Early postoperative and
      3-year follow-up photographs of representative younger, middle-aged, and older
      patients are shown.

PMID- 7634739
TI  - Extended SMAS dissection as an approach to midface rejuvenation.
AB  - The objective in rhytidectomy is to rejuvenate and improve facial appearance. To
      obtain consistent results, facelifting should be approached not just as a
      tightening or lifting procedure but also as a reconstructive procedure, reversing
      the anatomic changes that occur in aging. The ability to bring aesthetic harmony
      back into the aging face requires the blending of surgical technique, anatomic
      knowledge, and artistic sensitivity to individualize the surgical approach for a
      given patient. To obtain surgical rejuvenation while minimizing signs of surgical
      distortion remains the ultimate goal of our facelifting procedures.

PMID- 7634740
TI  - Composite rhytidectomy and the nasolabial fold.
AB  - In composite rhytidectomy, all of the deep aging anatomic components of the
      midface are elevated in the skin flap. The platysma muscle, cheek fat, and
      orbicularis oculi muscle are repositioned in this bipedicled musculocutaneous
      flap, which very effectively improves the nasolabial fold. Repositioning of all
      of the deep elements of the aging face and forehead is obligatory in creating a
      harmonious rejuvenation.

PMID- 7634741
TI  - Extended sub-SMAS dissection and cheek elevation.
AB  - The extended SMAS facelift techniques gave plastic surgeons the ability to
      correct the nasolabial fold and medial cheek. Retensioning the SMAS transmits the
      benefit through the multilinked fibrous support system of the facial soft
      tissues. The effect is to provide a recontouring of the ptotic soft tissues,
      which fills out the cheeks as it reduces nasolabial fullness. Indirectly, dermal
      tightening occurs to a lesser but more natural degree than with traditional
      facelift surgery. Although details of current techniques may be superseded, the
      emerging surgical principles are becoming more clearly defined. This article
      presents these principles and describes the author's current surgical technique.

PMID- 7634742
TI  - The subperiosteal approach for the correction of the deep nasolabial fold and the
      central third of the face.
AB  - The nasolabial fold is one of the most difficult problems to correct with the
      traditional skin-SMAS rhytidectomy. This article presents a technique for the
      correction of the deep nasolabial fold and the central third of the face. Key
      steps of the operation include (1) a wide subperiosteal dissection with extension
      under the intermediate temporal fascia and the fascia of the masseter muscle, (2)
      subperiosteal release of the lower margins of the malar and maxillary areas, and
      (3) upward lifting and fixation of the deep structures in an almost vertical
      orientation. These surgical principles can be applied to the open, pure
      endoscopic, or endoscopic-assisted biplanar facelift.

PMID- 7634743
TI  - Postprandial protein utilization and protein quality assessment in man.

PMID- 7634744
TI  - Adriamycin-related hypertension in pregnant rats: response to a thromboxane
      receptor antagonist.
AB  - 1. In previous works we have described the development of hypertension and
      aggravation of proteinuria in rats who became pregnant after the administration
      of Adriamycin. This was associated with an increase in the glomerular thromboxane
      B2-prostaglandin E2 ratio. 2. To assess the pathogenetic role of thromboxane in
      this model, female Wistar rats were mated 2 weeks after receiving Adriamycin (3.5
      mg/kg intravenously). Rats were then treated with the thromboxane-receptor
      antagonist daltroban, 60 mg day-1 kg-1 orally, beginning on day 11 of pregnancy.
      Systolic blood pressure, proteinuria and the urinary excretion of thromboxane B2,
      6-keto-prostaglandin F1 alpha and prostaglandin E2 were measured serially before
      mating, and on days 14 and 21 of pregnancy. The results were compared with those
      in Adriamycin-(treated) pregnant rats not treated with daltroban, Adriamycin
      treated virgin rats and normal virgin or pregnant rats either treated or
      untreated with daltroban. 3. In daltroban-treated pregnant and virgin rats
      treated with Adriamycin, systolic blood pressure remained normal, whereas it
      increased significantly (P < 0.05) in untreated animals. On day 14, blood
      pressure was higher in non-daltroban-treated Adriamycin-treated pregnant rats
      than in non-daltroban-treated Adriamycin-treated virgin rats. Treatment had no
      effect on blood pressure in normal virgin or pregnant rats. Proteinuria was
      higher in pregnant rats treated with Adriamycin than in Adriamycin-treated virgin
      rats, but it was not reduced by daltroban.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7634745
TI  - Microalbuminuria reflects a generalized transvascular albumin leakiness in
      clinically healthy subjects.
AB  - 1. In epidemiological studies microalbuminuria, i.e. slightly elevated urinary
      albumin excretion rate, predicts increased atherosclerotic vascular morbidity and
      mortality. This study aimed to test the hypothesis that microalbuminuria in
      clinically healthy subjects is associated with a systemic transvascular albumin
      leakiness. In animal experiments the outflux of albumin and lipids to the
      arterial wall are highly correlated, and both are elevated in atherosclerosis. 2.
      All participants were recruited at random from a population-based epidemiological
      study, where the upper decile of urinary albumin excretion rate was 6.6
      micrograms/min. Twenty-seven patients with persistent microalbuminuria (urinary
      albumin excretion rate 6.6-150 micrograms/min), and 56 age- and sex-matched
      control subjects with persistent normoalbuminuria (UAER < or = 6.6
      micrograms/min) were studied. 3. The systemic transvascular albumin leakage was
      measured as the fractional disappearance rate of 125I-labelled albumin from the
      total plasma compartment in 1 h after intravenous injection. 4. The fractional
      disappearance rate of albumin from the plasma compartment was higher in the
      microalbuminuric than in the normoalbuminuric group [5.8 (95% confidence interval
      5.3-6.2; n = 27) versus 5.0 (4.6-5.5; n = 56)%/h, P < 0.05]. The positive
      correlation between urinary albumin excretion rate on continuous scale
      (logarithmically transformed) and the fractional disappearance rate of albumin
      from the plasma compartment [slope 0.4 (95% confidence interval 0.1-0.7; n = 83),
      r = 0.29, P < 0.005] was independent of age, sex, smoking status, blood pressure,
      body size, plasma volume, plasma albumin concentration and concentrations of
      blood glucose, serum insulin and serum lipids. 5. In conclusion, microalbuminuria
      is an independent marker of systemic transvascular albumin leakiness in
      clinically healthy subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7634746
TI  - Effects of exercise and nitrates on blood flow in internal mammary artery to
      coronary artery grafts: a non-invasive study.
AB  - 1. The aim of the present study was to investigate the effects of exercise and of
      sublingual glyceryl trinitrate on the pattern of blood flow, as studied by
      Doppler ultrasound, in internal mammary artery grafts performed to relieve severe
      stenosis of the left anterior descending coronary artery. The accessibility of
      the graft to transcutaneous ultrasound examination allows the effects of exercise
      and nitrate administration on coronary blood flow to be studied non-invasively.
      2. Angina-free patients with left internal mammary to left anterior descending
      coronary artery grafts were studied using transcutaneous duplex ultrasound at
      rest, after leg exercise and after sublingual administration of 0.5 mg or 1 mg of
      glyceryl trinitrate. 3. Resting graft blood flow showed a biphasic pattern, with
      forward flow in both systole and diastole. Exercise caused an increase in time
      averaged velocity of graft blood flow from 17.3 (3.3) to 24.0 (7.2) cm/s (P =
      0.001), and of calculated volume flow from 44.7 (3.08) to 59.8 (5.89) ml/min (P =
      0.002). Diastolic peak velocity increased from 36.1 (9.9) cm/s to 46.8 (16.2)
      cm/s (P = 0.04), while peak systolic velocity was unchanged. Nitrate
      administration caused a fall in systolic and diastolic blood pressure and an
      increase in heart rate; graft flow was maintained [time-averaged velocity 18.3
      (6.2) cm/s before and 16.7 (5.7) cm/s after 500 micrograms of glyceryl
      trinitrate], but systole was shortened and the proportion of blood flow in
      diastole increased [systolic/diastolic flow ratio 0.558 (0.139) before and 0.374
      (0.156) after 500 micrograms of glyceryl trinitrate, P = 0.01].(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7634747
TI  - Comparison of arterial occlusion and ischaemic exercise for the study of
      vasodilatation in the human calf.
AB  - 1. Calf blood flow was measured by venous occlusion plethysmography to compare
      two stimuli for eliciting maximal calf vascular conductance: (i) 10 min of
      arterial occlusion and (ii) isolated exhaustive calf exercise with ischaemic
      occlusion. The subjects were semi-supine with the calf in position for immediate
      blood flow measurements after release of the occluding cuff. Three groups of
      subjects were studied: young [35 years (SD 9, n = 9)], old [57 years (SD 5, n =
      10)] and patients with congestive heart failure [63 years (SD 7, n = 7)]. 2.
      Occlusion and ischaemic exercise were equally effective in producing maximal calf
      vascular conductance in each of the subject groups. Maximal calf vascular
      conductance (ml min-1 100 ml-1 mmHg-1) was equivalent in the young [ischaemic
      exercise 0.54 (SEM 0.03), occlusion 0.54 (SEM 0.05)] and old [ischaemic exercise
      0.47 (SEM 0.05), occlusion 0.48 (SEM 0.04)] subjects. However, patients with
      congestive heart failure exhibited significantly reduced maximal calf vascular
      conductance [ischaemic exercise 0.20 (SEM 0.02), occlusion 0.20 (SEM 0.01)]. 3.
      Analysis of the curves, generated by plotting serial calf vascular conductance
      values obtained immediately and every 15 s after occlusion cuff release for 165
      s, revealed differences in the pattern of vasodilatation after occlusion and
      ischaemic exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7634748
TI  - A new non-invasive statistical method to assess the spontaneous cardiac
      baroreflex in humans.
AB  - 1. A new method was developed to evaluate cardiac baroreflex sensitivity. The
      association of a high systolic blood pressure with a low heart rate or the
      converse is considered to be under the influence of cardiac baroreflex activity.
      This method is based on the determination of the statistical dependence between
      systolic blood pressure and heart rate values obtained non-invasively by a
      Finapres device. Our computerized analysis selects the associations with the
      highest statistical dependence. A 'Z-coefficient' quantifies the strength of the
      statistical dependence. The slope of the linear regression, computed on these
      selected associations, is used to estimate baroreflex sensitivity. 2. The present
      study was carried out in 11 healthy resting male subjects. The results obtained
      by the 'Z-coefficient' method were compared with those obtained by cross-spectrum
      analysis, which has already been validated in humans. Furthermore, the
      reproducibility of both methods was checked after 1 week. 3. The results obtained
      by the two methods were significantly correlated (r = 0.78 for the first and r =
      0.76 for the second experiment, P < 0.01). When repeated after 1 week, the
      average results were not significantly different. Considering individual results,
      test-retest correlation coefficients were higher with the Z-analysis (r = 0.79, P
      < 0.01) than with the cross-spectrum analysis (r = 0.61, P < 0.05). 4. In
      conclusion, as the Z-method gives results similar to but more reproducible than
      the cross-spectrum method, it might be a powerful and reliable tool to assess
      baroreflex sensitivity in humans.

PMID- 7634749
TI  - The SA gene: predisposition to hypertension and renal function in man.
AB  - 1. The SA gene is expressed in the kidneys and is associated with hypertension in
      man and experimental animal models. Predisposition to hypertension is associated
      with renal haemodynamic abnormalities and increased renal SA gene expression. 2.
      We studied the distribution of the SA gene alleles (A1, A2), defined by the PstI
      polymorphism, in young adults with contrasting predisposition to hypertension to
      determine whether genetic variation at the SA gene locus is associated with
      variations in renal haemodynamics, electrolyte metabolism and the renin
      angiotensin system. 3. The frequency of the A2 allele was not significantly
      different between subjects with high personal and parental blood pressures and
      subjects with low personal and parental blood pressures. We detected no overall
      relationship between blood pressures and SA genotype, even after taking sodium
      intake into account. 4. Glomerular filtration rate, renal blood flow, renal
      vascular resistance, plasma volume, exchangeable sodium and total body water did
      not differ according to SA genotypes. Moreover, we detected no significant effect
      of SA genotype on circulating components of the renin-angiotensin system or
      atrial natriuretic peptide. 5. In our population, genetic variation at the SA
      gene locus defined by PstI polymorphism does not influence the renal
      characteristics that contribute to the development of hypertension.

PMID- 7634750
TI  - Down-regulation of vasopressin V1a receptor mRNA in diabetes mellitus in the rat.
AB  - 1. To investigate the mechanism of hepatic V1a vasopressin receptor down
      regulation in streptozotocin-induced diabetes mellitus in the rat, we measured
      hepatic V1a receptor mRNA by in situ hybridization histochemistry using
      oligonucleotide probes to the V1a receptor and Northern blotting. 2. Diabetes
      mellitus caused hyperglycaemia, hyperosmolality and increased plasma vasopressin
      concentrations (P < 0.01). Hepatocyte V1a receptor mRNA was reduced by 76% in
      diabetic rats (P < 0.01) and by 53% in insulin-treated diabetic rats (P < 0.01)
      versus control rats, in parallel with reduced V1a radioligand binding and
      vasopressin-stimulated inositol phosphates production. There was a similar
      decrease in hepatic V1a/18S mRNA density ratio in the diabetic and
      diabetic+insulin groups (both P < 0.05 versus control). 3. These findings suggest
      that altered V1a mRNA transcription is responsible for the reduced hepatic V1a
      receptor density in diabetes mellitus.

PMID- 7634751
TI  - Plasma semicarbazide-sensitive amine oxidase activity is elevated in diabetes
      mellitus and correlates with glycosylated haemoglobin.
AB  - 1. Semicarbazide-sensitive amine oxidase is a common name for a group of
      heterogeneous amine oxidases which are present in various mammalian tissues,
      especially in vascular smooth muscle cells, cartilage and adipose tissue, but
      also in plasma. 2. Plasma semicarbazide-sensitive amine oxidase activity was
      elevated in a group of 104 patients with insulin-dependent diabetes mellitus
      compared with normal control subjects (555 +/- 172 versus 352 +/- 102 m-units/l,
      P < 0.0005). 3. Plasma semicarbazide-sensitive amine oxidase activity was higher
      in subgroups with either retinopathy or nephropathy or both [583 +/- 116 (n =
      34), 581 +/- 229 (n = 10) and 646 +/- 249 m-units/l (n = 19), respectively] than
      in the subgroup without overt complications [486 +/- 129 m-units/l (n = 41), P <
      0.005]. 4. Plasma semicarbazide-sensitive amine oxidase activity was positively
      correlated with plasma glycosylated haemoglobin (r = 0.40; P < 0.0001) and with
      log urinary albumin excretion (r = 0.26; P < 0.025). 5. The possibility that
      semicarbazide-sensitive amine oxidase, by its conversion of endogenous amines
      like methylamine and aminoacetone into cytotoxic aldehydes, plays a role in the
      development of microvascular complications in diabetes mellitus, needs further
      investigation.

PMID- 7634752
TI  - Comparative effects of recombinant human insulin-like growth factor I and insulin
      on whole-body and forearm palmitate metabolism in man.
AB  - 1. The effects of intravenous infusions of recombinant human insulin-like growth
      factor I and insulin on palmitate kinetics, lipolysis and on serum
      triacylglycerol were compared. Overnight-fasted normal subjects received high
      doses of insulin-like growth factor I (30 micrograms h-1 kg-1) and insulin (0.23
      nmol h-1 kg-1; group 1), low doses of insulin-like growth factor I (5 micrograms
      h-1 kg-1) and insulin (0.04 nmol h-1 kg-1; group 2) or saline (control group).
      The doses of insulin-like growth factor I and insulin were equipotent with regard
      to increases in glucose uptake during 8 h euglycaemic clamping. 2. Whole-body
      palmitate flux (measured by continuous infusions of [2,2-D2]palmitate) was
      lowered dose-dependently by 68% +/- 6% during insulin-like growth factor I and by
      82% +/- 2% during insulin after 8 h of infusions of high doses (insulin-like
      growth factor I versus insulin; not significant). Plasma palmitate, glycerol and
      triacylglycerol concentrations had decreased to a similar extent at the end of
      the infusions of both peptides at either dose. 3. The present results demonstrate
      that insulin-like growth factor I and insulin infused at doses which result in
      identical increases in glucose uptake during euglycaemic clamping are equipotent
      inhibitors of lipolysis.

PMID- 7634753
TI  - Tricarboxylic acid cycle intermediates during incremental exercise in healthy
      subjects and in patients with McArdle's disease.
AB  - 1. The importance of the level of tricarboxylic acid cycle intermediates (malate,
      citrate and fumarate) for energy transduction during exercise has been
      investigated in six healthy subjects and in two patients with muscle
      phosphorylase deficiency (McArdle's disease). 2. Healthy subjects cycled for 10
      min at low (50 W), moderate [130 +/- 6 W (mean +/- SEM)] and high (226 +/- 12 W)
      work rates, corresponding to 26, 50 and 80% of their maximal O2 uptake,
      respectively. Patients with McArdle's disease cycled for 11-13 min at submaximal
      (40 W) rates, and to fatigue at maximal work rates of 60-90 W. 3. In healthy
      subjects, phosphocreatine was unchanged during low work rates, but decreased to
      79 and 32% of the initial level during moderate and high work rates. In patients
      with McArdle's disease, phosphocreatine decreased to 82 and 34% of the initial
      level during submaximal and peak exercise. Muscle lactate increased in healthy
      subjects during exercise at moderate and high work rates, but remained low in
      patients with McArdle's disease. 4. In healthy subjects, tricarboxylic acid cycle
      intermediates were similar at rest and at low work rates (0.48 +/- 0.04 mmol/kg
      dry weight), but increased to 1.6 +/- 0.2 mmol/kg dry weight and 4.0 +/- 0.3
      mmol/kg dry weight at moderate and high work rates. The tricarboxylic acid cycle
      intermediate level in patients with McArdle's disease was similar to that in
      healthy subjects at rest, but was markedly reduced during exercise when compared
      at the same relative intensity. The peak level of tricarboxylic acid cycle
      intermediates in patients with McArdle's disease was 22% of that in healthy
      subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7634754
TI  - Effect of extracellular potassium concentration on the sodium-potassium pump rate
      in human lymphocytes.
AB  - 1. The purpose of this study was to determine whether physiological changes in
      extracellular free [K+] cause significant changes in the Na(+)-K+ pump rate and
      intracellular free [Na+]. 2. The Na(+)-K+ pump rate was measured in human
      lymphocytes by determining ouabain-sensitive 86Rb+ influx at several
      concentrations of K+. The Na(+)-K+ pump rate increased within the physiological
      range of extracellular free [K+] (K1/2 = 1.5 mmol/l). 3. To test the hypothesis
      that elevation of extracellular free [K+] reduces intracellular free [Na+]
      rapidly, which in turn then slows the pump rate during experimental incubations,
      lymphocyte intracellular free [Na+] was measured using the fluorochrome sodium
      binding benzofuran isophthalate. With larger elevations of extracellular free
      [K+], intracellular free [Na+] dropped more rapidly. Thus previous discrepancies
      among determinations of K1/2 may be the result of variations in incubation times,
      which can skew the pump rates measured during incubations in various
      extracellular free [K+] values. Steady-state intracellular free [Na+] varied
      inversely with extracellular free [K+].

PMID- 7634755
TI  - Clinical significance of urinary ferritin excretion in patients with transitional
      cell carcinoma.
AB  - 1. The serum ferritin level provides a valuable index of the body iron store. An
      increase in serum ferritin has often been observed in patients with neoplastic
      disease and correlates well with the stage of cancer. A few studies have
      suggested the potential of urinary ferritin as a marker for transitional cell
      carcinoma. The rationale of the measurement, however, has not been investigated
      in detail. 2. Urinary ferritin levels were evaluated in patients with diverse
      urological diseases to investigate their potential clinical implications. 3.
      Analysis of logarithmic transformed values (ng/mg creatinine) showed that
      patients with both neoplastic and non-neoplastic urological diseases had
      significantly higher ferritin levels than normal control subjects (P = 0.02).
      There was no apparent difference between subgroups of patients with urological
      disease (P > 0.5). For patients with urothelial carcinoma, univariate analysis
      revealed a strong positive relationship between urinary ferritin levels and the
      density of lymphoid cells in tumour stroma (P = 0.0001), while no important
      association was observed with tumour grade (P = 0.32), stage (P = 0.29) or
      urinary cytology detection (P = 0.33). Patients with muscle-invasive tumour had
      significantly higher ferritin levels than those with papillary, superficial
      cancer (P < 0.05). For patients with non-neoplastic urological disease (n = 19),
      urinary ferritin levels tend to correlate with the severity of tissue
      inflammation (P = 0.03). 4. The results suggest that urinary ferritin may reflect
      the degree of local inflammatory reaction in the urinary tract.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7634756
TI  - Accuracy of breath-by-breath analysis of flow-volume loop in identifying sleep
      induced flow-limited breathing cycles in sleep apnoea-hypopnoea syndrome.
AB  - 1. Inspiratory flow limitation is involved in the pathophysiology of sleep
      related breathing disorders. Since the definition of flow-limited cycle is based
      on a dissociation between flow and respiratory efforts, identification of
      inspiratory flow limitation requires upper airway or intrathoracic pressure
      measurements. We examined the accuracy of the analysis of the flow-volume loop of
      a tidal breath in identifying inspiratory flow limitation during sleep in ten
      patients with a sleep apnoea-hypopnoea syndrome. 2. Measurements were taken
      during continuous positive airway pressure trials. After data acquisition, the
      presence of inspiratory flow limitation was identified by the presence of an
      inspiratory plateau or decrease in inspiratory flow independently of the increase
      in inspiratory efforts. The flow-volume loop was reconstructed for each breathing
      cycle by plotting the instantaneous flow and the tidal volume. The instantaneous
      inspiratory and expiratory flows were measured at 50% of the respective portion
      of the tidal volume, and a breath-by-breath analysis of the mid-tidal volume-flow
      ratio (inspiratory/expiratory ratio) was obtained. The analysis of the flow
      volume loop was compared with standard inspiratory flow limitation criteria using
      different values of the inspiratory/expiratory ratio threshold, below which
      breathing cycles were classified as flow-limited. With a lower limit of the
      normal inspiratory/expiratory ratio threshold of 0.97, the sensitivity and
      specificity of the method were both 76%. In each subject, the proportion of
      breathing cycles identified as flow-progressively decreased with an increasing
      positive pressure level.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7634757
TI  - Biosynthesis of platelet-activating factor in normal and inflamed human colon
      mucosa: evidence for the involvement of the pathway of platelet-activating factor
      synthesis de novo in inflammatory bowel disease.
AB  - 1. Platelet-activating factor can be synthesized by two distinct biochemical
      pathways and is degraded by a number of enzymes, the first step of which is
      deacetylation by a specific acetyl hydrolase. 2. The biochemical pathway of
      platelet-activating factor synthesis de novo and the first step in platelet
      activating factor degradation have been investigated for the first time in
      incubates of normal human colon mucosa and in inflamed mucosa from patients with
      inflammatory bowel disease. 3. In the presence of 100 mumol/l CDP-choline and 100
      mumol/l hexadecyl acetyl glycerol, homogenates from inflamed mucosa synthesized
      significantly greater platelet-activating factor [851 +/- 574 pmol/mg of protein
      (mean +/- SEM) in 90 min incubation] than normal mucosa [105 +/- 61 pmol/mg of
      protein in 90 min incubation] (P < 0.05). 4. Under the same conditions of assay,
      the percentage turnover to inactive lyso-platelet-activating factor was similar
      in inflamed mucosa (35.5 +/- 9.4%) and normal mucosa (42.7 +/- 8.5%) in 90 min (P
      > 0.05). 5. The identity of platelet-activating factor was confirmed by HPLC, by
      its mobility on TLC and by the ability of WEB 2170, a selective platelet
      activating factor receptor antagonist, to block its platelet-aggregatory action.
      6. These findings confirm the presence of the pathway for the synthesis de novo
      of the potently proinflammatory platelet-activating factor in human colon mucosa
      in inflammatory bowel disease.

PMID- 7634758
TI  - Long-term fructose versus corn starch feeding in the spontaneously hypertensive
      rat.
AB  - 1. Fructose feeding, as opposed to vegetable starch feeding, has been shown to
      elevate blood pressure and to decrease insulin sensitivity in normotensive rats.
      The long-term relevance of this is unclear, and data in hypertensive strains are
      scarce. 2. We studied the effects of 27 weeks of a fructose-versus a corn-starch
      enriched (69.5% w/w) diet in the spontaneously hypertensive rat. 3. In both
      dietary groups, blood pressure increased with ageing, with no apparent difference
      between the diets. The fructose-fed rats gained less weight. However, even
      selecting fructose-fed rats that matched the weight gain in the corn starch
      group, did not reveal a significant elevation of systolic blood pressure over
      time. 4. Extracellular fluid volume was comparable in fructose-fed and corn
      starch-fed rats. No effects on creatinine clearance, proteinuria or renal
      histology were found. Fasting values of plasma triacylgycerols and cholesterol
      were increased mildly after 2 weeks on the fructose diet. However, fasting
      glucose and insulin measured after 2 weeks, and the response to an
      intraperitoneal glucose load, were no different. After 23 weeks of the diets,
      fasting values of plasma glucose, insulin, triacylglycerols and cholesterol did
      not differ. There were small differences in the response of plasma glucose levels
      to the intraperitoneal glucose load, but the area under the curve was not
      different. The baseline insulin resistance present in spontaneously hypertensive
      rats possibly blunts the metabolic response to dietary fructose. 5. After 27
      weeks, the diets were switched in cross-over design, and measurements were
      continued until 39 weeks. The fructose diet did not elevate systolic blood
      pressure in this follow-up experiment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7634759
TI  - Use of a stable copper isotope (65Cu) in the differential diagnosis of Wilson's
      disease.
AB  - 1. 65Cu/63Cu stable-isotope ratios have been measured in blood serum after oral
      administration of the stable isotope 65Cu. The incorporation of the isotope into
      the plasma protein pool was followed at various times for up to 3 days. The
      resulting patterns of enrichment in healthy control subjects, in Wilson's disease
      patients and in heterozygotes for the Wilson's disease gene, were similar in
      appearance to those found by others using copper radioactive isotopes. After an
      initially high enrichment at 2 h after dosage, the Wilson's disease cases, in
      contrast to the control subjects, did not show a secondary rise in isotope
      enrichment of the plasma pool after 72 h, demonstrating a failure to incorporate
      copper into caeruloplasmin. The Wilson's disease heterozygotes had variable
      degrees of impairment of isotope incorporation, not always distinguished from
      those of control subjects. 2. The stability of the isotope also permits the
      copper tracer to be followed for a longer period. Ten healthy subjects were
      studied for over 40 days, allowing the biological half-time of an oral dose of
      copper to be determined (median 18.5 days, 95% confidence interval 14-26 days).
      Known heterozygotes for the Wilson's disease gene were found to have a
      significantly increased biological half-time for removal of copper from the
      plasma pool (median 43 days, 95% confidence interval 32-77 days). 3. The
      incorporation of 65 Cu in patients with diseases of the liver (other than
      Wilson's disease) was found to be similar to that in control subjects, aiding
      differential diagnosis.

PMID- 7634760
TI  - Resolving attachment ambiguities with multiple constraints.
AB  - Different theories of syntactic ambiguity resolution argue for different sources
      of information determining initial parsing decisions (e.g., structurally defined
      parsing principles, lexically specific biases, or referential pragmatics).
      However, a "constraint-based" approach to syntactic ambiguity resolution proposes
      that both lexically specific biases and referential pragmatics are used in
      parallel by the comprehender. Analyses of text corpora, sentence fragment
      completions, and self-paced reading experiments were conducted to demonstrate
      that both local information (lexically specific biases) and contextual
      information (referential presupposition) contribute to the on-line resolution of
      prepositional phrase attachment ambiguities. There does not appear to be a role
      for purely structurally defined parsing principles (i.e., minimal attachment).
      Present and previous evidence is consistent with a developing framework in which
      multiple constraints (bottom-up and top-down) interact immediately to determine
      initial syntactic commitments.

PMID- 7634761
TI  - Microstructural musical linguistics: composers' pulses are liked most by the best
      musicians.
AB  - Western music is a combination of notated structure plus microstructure.
      Composers' pulses, as precise microstructural functions, were tested with five
      groups of subjects of graded musical proficiency: (1) 10 famous artists including
      Vladimir Ashkenazy, Yehudi Menuhin, Paul Badura-Skoda and others; (2) 14 Julliard
      School of Music graduate students; (3) 19 Manhattan School of Music graduate
      students; (4) 51 Australian conservatory students; and (5) 41 non-music students
      (total, 135 subjects). Composers' pulses consist of combined amplitude and timing
      warps specific to each composer--the composer's pulse matrix. Each subject
      listened to and scored 40 versions of 10 short music examples (not selected by
      the author) of eight bars each, composed by Beethoven, Mozart, Haydn and
      Schubert, performed by computer, in which composers' pulses, as developed by
      Clynes (1983, 1985a,b, 1986, 1987), were incorporated in a two-level hierarchic
      pulse configuration, and interchanged. Each example was heard with the pulses of
      those four composers in turn, in quasi-random sequence, one performance thus
      incorporating the "right" pulse and three the "wrong" ones. Results show
      dramatically that the greater the musical proficiency, the more marked the
      preference for the "right" pulse (p < .0001). Non-musicians as a group showed a
      similar tendency of preference, but typically to a considerably less pronounced
      degree. Further studies suggest that longer excerpts (32 bars) and repeated
      hearing would help non-musicians also to better understand composers' pulses. A
      theory of music as a double stream is introduced. The results suggest that the
      composers' pulse matrices posited by Clynes as a first approximation are in fact
      appropriately meaningful. Brain function aspects of the meaningful discrimination
      of such tiny time differences are discussed.

PMID- 7634762
TI  - When passives are easier than actives: two case studies of aphasic comprehension.
AB  - We outline a range of previous theoretical accounts of agrammatic comprehension
      in patients with Broca's aphasia. Specific attention is paid to patterns of
      preserved and impaired understanding of reversible actives and passives. We note
      that no prior account will allow for the existence of patients who show better
      comprehension of passives than actives. In three experiments, we compare and
      contrast the performance of two patients whose syntactic comprehension ability is
      in complementary distribution. The first patient (M.H.) performs well on simple
      actives, active questions, and active existentials, but is below chance on their
      corresponding passives. The second patient (B.M.) is at chance on simple actives,
      active questions and active existentials while scoring significantly above chance
      on their respective passives. We interpret both patterns of response in terms of
      the distinction drawn by Case theory between structural and inherent Case. The
      first patient's grammar cannot assign either structural or inherent Case and she
      must accordingly apply a non-linguistic linear strategy to assign thematic roles
      in all sentences. The second patient (B.M.) has a specific impairment of
      structural Case; he can accordingly not interpret actives (where Case is assigned
      configurationally) but can interpret passives (where Case is assigned lexically).

PMID- 7634763
TI  - Syntactic cues in the acquisition of collective nouns.
AB  - One basic finding in the study of word learning is that children tend to construe
      a word describing an object as referring to the kind of whole object, rather than
      to a part of the object, one of its properties, or the substance it is made of.
      This has been taken as evidence that there exist certain special constraints on
      word meaning that guide children to favor the kind-of-object interpretation when
      exposed to a new word. There are descriptive problems with this proposal,
      however, as it cannot explain how children learn other kinds of words, such as
      names for specific people, substances, parts, events, collections, and periods of
      time. These problems motivate an alternative theory in which young children
      possess several distinct conceptual categories--including "individual", which is
      more abstract than "whole object"--and can use syntactic cues to determine the
      conceptual category that a new word belongs to. This theory is explored in two
      experiments in which we attempt to use syntactic cues to teach children and
      adults novel collective nouns--words that refer to groups of objects. The results
      indicate that children can use such cues to learn names for kinds of individuals
      that are not whole objects, although they are less able to do so than adults.
      Candidate explanations for why this developmental difference exists are discussed
      and implications are drawn for theories of word learning and conceptual
      representation.

PMID- 7634764
TI  - Making explicit 3-year-olds' implicit competence with their own false beliefs.
AB  - Three-year-olds usually fail to recall a previous false belief once they have
      discovered the true state of affairs. The failure is so dramatic that researchers
      have treated it as a case of functional retrograde amnesia. We found in a series
      of studies that the memory trace is indeed available but is inaccessible under
      traditional testing procedures. We also provided a new prediction that reminding
      children that they had briefly held a picture of an object would be a more
      powerful retrieval cue than a reminder that they had held the small object
      itself. It was further shown that an effective picture was one that reminded
      children of the content of the target belief and not one that would enable them
      to reconstruct the contextual cause of why they had held the belief--a case of
      "recall without insight". However, there was evidence that successful recall was
      associated with either (a) an insight that the recall was of a thought rather
      than of a pretence (delayed post-test technique) or (b) a readiness to attach a
      mentalistic label to the recall (immediate post-test technique). The results
      serve to narrow an assessment of the competence gap between 3- and 4-year-olds in
      recall of their own false belief. Rather than a sudden ability to preserve the
      memory in association with insight into its informational origins, it is only the
      latter that comes on stream in 4-year-olds. Alternative explanations of the
      picture facilitation effect suggest different research strategies, each of which
      aims at a gap in current formulations of false belief recall.

PMID- 7634765
TI  - Learning and morphological change.
AB  - An account is offered to change over time in English verb morphology, based on a
      connectionist approach to how morphological knowledge is acquired and used. A
      technique is first described that was developed for modeling historical change in
      connectionist networks, and that technique is applied to model English verb
      inflection as it developed from the highly complex past tense system of Old
      English towards that of the modern language, with one predominant "regular"
      inflection and a small number of irregular forms. The model relies on the fact
      that certain input-output mappings are easier than others to learn in a
      connectionist network. Highly frequent patterns, or those that share phonological
      regularities with a number of others, are learned more quickly and with lower
      error than low-frequency, highly irregular patterns. A network is taught a data
      set representative of the verb classes of Old English, but learning is stopped
      before reaching asymptote, and the output of this network is used as the teacher
      of a new net. As a result, the errors in the first network were passed on to
      become part of the data set of the second. Those patterns that are hardest to
      learn led to the most errors, and over time are "regularized" to fit a more
      dominant pattern. The results of the networks simulations were highly consistent
      with the major historical developments. These results are predicted from well
      understood aspects of network dynamics, which therefore provide a rationale for
      the shape of the attested changes.

PMID- 7634766
TI  - Community risk indicators for dental caries in school children: an ecologic
      study.
AB  - A statewide survey of NC schoolchildren found wide variation in dental caries
      prevalence among sampled classrooms. This study examined factors associated with
      this variation using classrooms as a surrogate for the larger community, in order
      to identify community risk indicators (CRI). In all, 172 classrooms (3400
      students) in Grades K-6 were available for analysis. Initially, 56
      sociodemographic, environmental, health system, and clinical factors were
      evaluated for their association with caries prevalence (K-3: average dfs + DMFS;
      4-6: average DMFS) using univariate and bivariate analyses. Of these, 21 factors
      met our criteria for evaluation using WLS multivariate regression. For Grades K-3
      (n = 108), population density, parental education, and coastal residence were
      negatively associated with caries scores, while age, and medical and dental,
      Medicaid expenditures were positive. For Grades 4--6 (n = 64), age and fs:dfs
      ratio were positively associated with caries scores while population density,
      population:dentist ratio, and years of natural fluoride exposure were negative.
      CRIs for both models, when compared to individual models, explained a substantial
      portion of the variation in caries prevalence, 31% for Grades K-3 and 51% for
      Grades 4-6. Results suggest that a risk assessment model based on community
      rather than individual variables is feasible and further refinement may reveal
      factors useful in identifying high risk communities.

PMID- 7634767
TI  - Caries experience in Latvian nursery school children.
AB  - In 1993 the dental health was assessed in 631 Latvian 3--4-yr-old nursery school
      children. Forty-eight percent of the 3-yr-olds and 26% of the 4-yr-olds were
      caries free. The mean dmft for the total sample was 3.2 (2.2 and 3.8 in the 3-and
      4-yr-olds, respectively). Molar caries, accounting for 66% of the total dmft
      score, was dominant in both age groups. Sixteen percent of the children had
      received restorations, 38% of which manifested recurrent caries. Recurrent caries
      was relatively more frequent in the younger children. Concomitant with a general
      increase in caries level, the polarization of the disease was less pronounced in
      the older children. The upper 25% of the distribution for 3- and 4-yr-olds
      contained 74% and 40% of the dmft, respectively. Daily toothbrushing was reported
      for 60% of the children. Of those, 38% used fluoride-containing dentifrice. No
      significant associations were found between caries experience and toothbrushing
      frequency, use of fluoride dentifrice or parents' education.

PMID- 7634768
TI  - Sugar consumption and caries risk in schoolchildren with low caries experience.
AB  - This paper assesses the risk from sugar consumption in a population of school
      children with low caries experience. It relates eight different measures of sugar
      consumption to the occurrence of any DMFS increment, and, separately, to
      approximal and pit-and-fissure DMFS. The data are from a 3-yr longitudinal study
      of 429 children, initially aged 11-15, residing in non-fluoridated rural
      communities in Michigan, USA. All children completed at least three dietary
      interviews, were present for baseline and final dental examinations, and had a
      parent or guardian provide questionnaire information on residence history, use of
      fluoride and dental services, and family history. Results indicated that a higher
      proportion of total energy intake from sugars increased the probability of caries
      on all surfaces, and a higher total intake of sugars was also associated with
      total caries increment. No relationship, however, was found between DMFS
      increment and the frequency of eating high sugar foods. Each additional 5 g of
      daily sugars intake was associated with a 1% increase in the probability of
      developing caries, and those whose energy intake from sugars was 1 SD above the
      mean had 2.0 times the risk of developing approximal caries than did children
      whose energy intake from sugars was 1 SD below the mean.

PMID- 7634769
TI  - Oral health in adolescents from a small French town.
AB  - In France, caries are more prevalent in rural areas than in large cities. This
      study analyzed the relationship between number of oral health indices and some
      known risk factors (toothbrushing, sugar consumption, saliva components) and
      sociodemographic factors in adolescents from a small town. The sample included
      112 children aged 12-14 in the north-east of France. School marks was found to be
      better linked with dental caries indices than the socio-occupational category of
      parents: gingival index (GI), DMFS, DMFT and caries severity (CS) significantly
      increased with decreasing school marks; oral plaque was related to socio
      occupational of parents. The analysis using the regression method showed that the
      variance explained by the various factors studied was modest (between 23 and 30%)
      for GI, initial caries sites (IS), DS, DMFS, DMFT and CS, and was small for
      plaque (5%) and calculus (3%). This would be due in part to the wide dispersion
      of these indices. The sex had a non-significant regression coefficient for all
      oral health indices investigated. For GI, only mutans streptococci (MS) and
      plaque had a significant regression coefficient. Calculus was explained by any
      factor considered. Only MS had a significant part in plaque. IS was explained by
      MS, toothbrushing and age. For DS, only toothbrushing, MS and sweet drinks during
      meals had a significant part. DMFS and DMFT were explained only by MS and age. CS
      was explained by MS, age, salivary buffer pH, salivary flow rate, and
      toothbrushing.

PMID- 7634770
TI  - Association of lifestyle with periodontal health.
AB  - All the 1012, 55-yr-old citizens of Oulu (a medium-sized Finnish town) were
      invited to a clinical examination, and 780 of them participated. The associations
      of lifestyle with periodontal health were analyzed in the 527 dentate subjects.
      Periodontal pockets deeper than 3 mm were recorded as a percentage of the
      surfaces at risk. Lifestyle was measured by questions about dietary habits,
      smoking habits, alcohol consumption and physical activity. Lifestyle had an
      independent association with periodontal health. Periodontal pocketing increased
      with an unhealthier lifestyle. Lifestyle could explain some of the social and sex
      differences in periodontal health.

PMID- 7634772
TI  - Patients' perceptions of the decision-making process leading to extraction of
      permanent teeth in Norway.
AB  - Extraction is the final step in a continuous process in which oral health-related
      factors and psycho-social processes play a role. The purpose of the present study
      was to investigate the patient's perception of the decision-making process
      leading to the extraction of permanent teeth and to determine whether and how
      patient-associated characteristics might influence who made the decision to
      extract and if the patients felt they had any influence on the dentist's
      decision. A national random sample of Norwegian dentists (n = 500) recorded
      reasons for tooth extraction during a period of 2 weeks in 1988. A total of 437
      patients responded (73%), of whom 54% were women. Nearly 33% of the respondents
      stated that it was their own decision to extract, while about two thirds said
      that the dentist had suggested extraction. Whether the dentist or the patient
      made the decision to extract teeth was significantly influenced by the patient's
      dental attendance pattern, place of residence, number of teeth and belief in
      retention of his/her own teeth for life (P < 0.05). There was no significant
      bivariate effect of patients' age, sex, educational level, or score on Corah's
      Dental Anxiety Scale on who made the decision to extract. Only 0.4% of patients
      said that family, friends or colleagues had influenced the decision to have teeth
      extracted. A logistic regression analysis with: "Was it the dentist or the
      patient who made the suggestion to extract teeth?" as the dependent variable, and
      the four bivariately significant independent variables showed for all patients
      that none had a significant effect.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7634771
TI  - Costs of periodontal and prosthodontic treatment and evaluation of oral health in
      patients after treatment of advanced periodontal disease.
AB  - Retrospective estimations of dental care costs of periodontal and prosthodontic
      treatment and evaluation of oral health in 37 patients with advanced periodontal
      disease were carried out. Measures of their subjective evaluation of oral health
      7-10 yr after the treatment are presented as a health profile and as indices in
      single numbers. The relations between oral health as an index and the dimensions
      in the health profile are analyzed. Dental care costs for treatment in the
      mandible was SEK 35 550, for the maxilla SEK 45 380 and for both jaws SEK 74 230.
      After the treatment oral health as well as general health were in excess of 75 on
      a 0 to 100 scale. Chewing ability, comfort and aesthetics were the variables
      found to significantly affect the subjective oral health. Oral health in terms of
      periodontal and prosthodontic conditions was maintained over the observation
      period.

PMID- 7634773
TI  - Dutch students' dental anxiety and occurrence of thoughts related to treatment.
AB  - The present study was intended to explore the relationship between individuals'
      level of dental anxiety and thoughts (both self-statements and mental images)
      related to dental treatment. Subjects were 210 psychology students (75 males, 135
      females). The results showed that 98% of the subjects reported one or more
      negative or catastrophic thoughts. A significant positive relationship was found
      between reported severity of anxiety (S-DAI scores) and frequency of thoughts.
      The results indicate that dental anxiety is associated with the tendency to
      experience negative or threatening thoughts concerning treatment.

PMID- 7634774
TI  - Calibration of dentists in the use of occlusal indices.
AB  - Dentists' opinions as to both need for and outcome of orthodontic treatment show
      wide variation. Within the profession there is an opportunity to reduce
      subjective bias and standardise criteria by the use of occlusal indices. The
      results of this study demonstrate that a group of dentists can easily be trained
      to record the Aesthetic and Dental Health Components of the Index of Orthodontic
      Treatment Need and the PAR index to a satisfactory level.

PMID- 7634775
TI  - Occupational health problems among dental hygienists.
AB  - A questionnaire survey on work-related health complaints was performed among
      dental hygienists. Valid information was received fom 189 hygienists,
      representing about half of all active members of the Norwegian Association of
      Dental Hygienists. Parallel information was received from similar number of
      female and male control persons in other occupations. The present report presents
      data on the nature and etiology of the chemically induced health complaints.
      About half of the hygienists had experienced one or more health problem of
      dermal, systemic, sensory (eye) or respiratory nature during the last year, as
      compared to 37% of the female and 19% of the male control group. The most
      frequent complaint was dermatoses of hands and fingers (37%), caused by different
      chemical, work-related factors. Latex gloves were responsible for 1/3 of these
      reactions. The role of immunological and irritant latex reactions were discussed
      and the prevalence of non-dermatological reactions compared with similar findings
      among women in other occupations.

PMID- 7634776
TI  - Energy intake, dental caries and periodontal disease in 11-year-old black
      children in two regions of Southern Africa: KwaZulu and Namibia.
AB  - The study examined energy intake in relation to dental caries and periodontal
      disease in 11-yr-old rural and urban black children in low fluoride areas of
      KwaZulu and Namibia (0.15 ppm F) and one higher fluoride area of Namibia (1.56
      ppm F). Twenty-four hour dietary recalls were conducted by trained interviewers
      and daily energy intake estimated using the MRC dietary analysis programme. DMFS
      was recorded according to WHO criteria: periodontal disease was measured using
      CPITN and SAS was used for statistical analysis. The prevalence of dental caries
      and periodontal disease (using CPITN), were compared within three energy
      groupings; < or = 850 kcal/day; > 850, < 1400 kcal/day and > or = 1400 kcal/day.
      The rural low fluoride Namibian children had the lowest mean energy intake (616
      kcal/day), which also was the grouping with highest healthy periodontal
      prevalence (65%). The urban groups had higher energy intakes than the rural
      communities. Statistically significant effects on caries prevalence were seen for
      country and fluoride grouping; for periodontal disease, significant effects were
      noted for country, fluoride group and environment. Energy intake had no
      statistically significant effect, so this is not a risk marker for the disease.

PMID- 7634777
TI  - Attitudes and knowledge of Indian dental professionals about HIV infection and
      AIDS.

PMID- 7634778
TI  - The prevention of nickel contact dermatitis. A review of the use of binding
      agents and barrier creams.
AB  - Chelating agents and other substances can be used to bind nickel or reduce its
      penetration through the skin, and hence to reduce the symptoms in subjects with
      nickel sensitivity. Topical usage is mostly described but, in some studies,
      chelating agents have been given systemically. The most effective ligand for
      nickel so far described is 5-chloro-7-iodoquinolin-8-ol. Although normally
      regarded as safe, its usage in some situations may be limited by concerns about
      its toxicity. Other ligands with demonstrable effect include
      ethylenediaminetetraacetic acid in various forms, diphenylglyoxime and
      dimethylglyoxime. Cation exchange resins can effectively bind nickel and work
      both in vitro and in vivo. Propylene glycol, petrolatum and lanolin reduce the
      absorption of nickel through the skin. Corticosteroids and cyclosporin work in
      nickel dermatitis by suppressing the immunological reaction rather than through
      an effect on nickel. Studies of the oral administration of ligands such as
      tetraethylthiuram disulphide have given conflicting results but the use of these
      agents is limited by hepatoxicity in any case. Some compounds offer potential for
      use in the prophylaxis of nickel dermatitis. Further work is required to develop
      the existing agents and to look at the use of novel combinations, such as that of
      a cation exchanger with a ligand.

PMID- 7634779
TI  - Testing with fragrance mix. Is the addition of sorbitan sesquioleate to the
      constituents useful?
AB  - In a multicentre study, the value of adding sorbitan sesquioleate (SSO) to the
      constituents of the 8% fragrance mix (FM) was investigated. In 7 centres, 709
      consecutive patients were tested with 2 types of FM from different sources, its 8
      constituents with 1% SSO, its 8 constituents without SSO, and 20% SSO. 5 patients
      (0.71%) reacted to the emulsifier SSO itself, read as definitely allergic on day
      3/4. 53 patients reacted to either one of the mixes with an allergic type of
      reaction. When tested with the constituents without SSO, 41.5% showed an allergic
      reaction versus 54.7% with SSO. If both types of reactions were considered
      (allergic and irritant) 38.3% of 73 patients showed a positive "breakdown" result
      without SSO, versus 54.8% with SSO. The differences were statistically
      significant. Reactivity to FM constituents was changed in a specific pattern by
      addition of SSO--irritant reactions increased, particularly for cinnamic alcohol,
      eugenol, geraniol, oak moss and hydroxycitronellal, whereas others showed only a
      slight change. Allergic reactions were also increased by SSO, but the rank order
      of the top 3 sensitizers (isoeugenol, oak moss and eugenol) did not change.
      Cinnamic alcohol was the only constituent with decreased reactivity after
      addition of SSO. A positive history of fragrance sensitivity (HFS) was clearly
      associated with a positive allergic reaction to either the mix or 1 of its
      constituents (51% versus 28.6% with a negative HFS). Irritant reactions were
      linked to a negative HFS in a high proportion (64.3%).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7634781
TI  - Contact sensitivity to menthol and peppermint in patients with intra-oral
      symptoms.
AB  - We report 12 cases of contact sensitivity to the flavouring agents menthol and
      peppermint oil in patients presenting with intra-oral symptoms in association
      with burning mouth syndrome, recurrent oral ulceration or a lichenoid reaction.
      The patients were referred from the Glasgow Dental Hospital over a 4-year period
      for assessment of the possible contribution of contact sensitivity to their
      complaints. 5 patients with burning mouth syndrome demonstrated contact
      sensitivity to menthol and/or peppermint, with 1 patient sensitive to both
      agents, 3 positive to menthol only and 1 to peppermint only. 4 cases with
      recurrent intra-oral ulceration were sensitive to both menthol and peppermint. 3
      patients with an oral lichenoid reaction were positive to menthol on patch
      testing, with 2 also sensitive to peppermint. 9 of the 12 cases demonstrated
      additional positive patch test results. After a mean follow-up of 32.7 months
      (range 9-48 months), of the 9 patients that could be contacted, 6 patients
      described clearance or improvement of their symptoms as a consequence of
      avoidance of menthol/peppermint.

PMID- 7634780
TI  - Are opera-house artistes afflicted with contact allergy to colophony and
      cosmetics?
AB  - The frequencies of cosmetics intolerance and contact allergy to colophony were
      investigated among 116 singers and dancers and 16 make-up artists. Participants
      were interviewed, examined and patch tested with a standard series and materials
      from the opera house. Common skin lesions were found in 1/3 of participants and
      more than 50% had a history of intolerance to cosmetics. Colophony gave positive
      patch test reactions in only 3 subjects. The prevalence of positive patch test
      reactions to fragrance mix and balsam of Peru was about the same as among
      dermatitis patients generally. Contact allergy to colophony did not seem to be a
      problem regarding cosmetics.

PMID- 7634782
TI  - Airborne irritant contact dermatitis from metal dust adhering to semisynthetic
      working suits.
AB  - 2 workers at an aircraft factory were employed in a plasma sparying unit. Soon
      after they were equipped with new semisynthetic working suits, they started to
      complain of pruritic eruptions after heavy exposure to metal dust. They noted
      that the dust was not as easily blown off the clothes by pressurized air as
      previously. Clinical findings consisted of discrete macular and papular lesions,
      partly follicular, on the ventral and medial thighs. Atopy score, IgE level and a
      standard series of prick tests ruled out atopic disposition. Patch tests revealed
      no reactions. A diagnosis of occupational airborne irritant contact dermatitis
      from metal dust was therefore made. To elucidate the role of the working suit,
      extensive physical investigations of the physical properties of the textile were
      performed. Microscopic pictures at low magnification showed more dust particles
      on the semisynthetic working suit, compared to the former pure cotton suit. This
      impression could not be confirmed by particle count because of too uneven
      particle distribution at higher magnification. Hairiness of the 2 textiles was
      low and ruled out irritation by the semisynthetic textile itself. No difference
      in electrostatic properties between the 2 working suits could be established
      either. Both textiles showed high static electrical propensity. When use of the
      semisynthetic overall was discontinued, the patients reported no
      recurrence.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7634783
TI  - Concomitant positive patch test results with standard screening tray in North
      America 1985-1989.
AB  - Responses to patch test substances may occur contemporaneously. Such simultaneous
      reactions may reflect concomitant sensitization to 2 dissimilar allergens to
      which concurrent exposure has taken place (e.g., ethylenediamine dihydrochloride
      and neomycin). It may occur when the individual has been exposed to only 1 of the
      substances and exhibits a response to other substances of similar chemical
      structure (i.e., cross-sensitization such as between para-phenylenediamine and
      benzocaine). Such simultaneous responses may also be chance occurrences,
      reflecting multiple sensitization or the result of altered response due to the
      "angry back syndrome". This investigation established that such concurrence of
      response is not uncommon and adds further documentation to the literature of
      these associations in patch test responses.

PMID- 7634784
TI  - Efficacy of topical corticosteroids on irritant skin reactions.
AB  - Topical corticosteroids are frequently used in the treatment of irritant contact
      dermatitis (ICD). The efficacy of this treatment has, however, not been
      thoroughly established, and experimental studies on the topic have provided
      conflicting results. The aim of the present study was to evaluate the effect of
      potent topical corticosteroids on experimentally-induced irritant skin reactions
      in a double-blind, vehicle-controlled study. 16 healthy volunteers had sodium
      lauryl sulfate patch tests symmetrically applied to the upper arms. After removal
      of patch tests, a potent topical corticosteroid (betamethasone-17-valerate) was
      applied to the irritant skin reaction on one arm, while the corresponding vehicle
      was applied to the irritant skin reaction on the opposite arm 2x daily for 7
      days. Reactions were evaluated by measurement of transepidermal water loss (TEWL)
      and erythema. After 7 days, statistically significant lower values of TEWL and
      erythema were found in corticosteroid-treated, compared to the vehicle-treated,
      skin reactions. The results indicate that topical corticosteroids improve healing
      of ICD.

PMID- 7634785
TI  - Detection of IgE antibodies to latex allergens in human serum.
AB  - Reports indicate increasing incidence of Type I allergic reactions to latex
      allergens. The proteins that act as allergens and produce such allergic reactions
      are found in the natural latex sap of Hevea brasiliensis. All those who are
      exposed to latex products, particularly healthcare workers, are potentially at
      risk. The lack of qualified allergen extracts makes it difficult to perform skin
      testing on individuals who are at high risk. Therefore, a reliable in vitro test
      system for the detection of IgE antibodies to latex would be of considerable
      utility. We have developed a serological test for the qualitative determination
      of specific IgE antibodies to latex. In our study, 75 sera from individuals with
      a history of latex allergy and 29 serum samples from healthcare workers were
      tested by both radioimmunoassay (RIA) and enzyme immunoassay (EIA). The allergen
      bound to paper discs was the same solid phase for the RIA and EIA assays. The
      allergen preparation used for coating the paper discs was a mixture of proteins
      obtained from raw latex. The data show a good correlation between the results of
      RIA and EIA methods with data obtained using an RIA assay at an independent
      laboratory and by skin prick testing. Comparing the performance of our test using
      our latex material with that of the latex material obtained from the Food and
      Drug Administration (FDA), along with results of other tests including skin
      tests, we found that the specificity and sensitivity of our assay method
      approaches 100%. The data show no significant cross-reactivity between latex and
      banana. A low level of cross-reactivity between latex and avocado was
      observed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7634786
TI  - Sensitivity to diaminodiphenylmethane.

PMID- 7634787
TI  - Contact allergy due to methyl glucose dioleate.

PMID- 7634788
TI  - Photoallergic contact dermatitis from the sunscreen ethylhexyl-p-methoxycinnamate
      (Parsol MCX).

PMID- 7634790
TI  - Occupational allergic contact dermatitis from nitrofurazone.

PMID- 7634789
TI  - Anaphylactic intraoperative reaction to latex.

PMID- 7634791
TI  - Contact dermatitis due to occupational dibutylthiourea exposure: a case of
      phonecard dermatitis.

PMID- 7634792
TI  - Occupational allergic contact dermatitis associated with curious public nickel
      dermatitis from minimal exposure.

PMID- 7634793
TI  - EPI-check: a new patch test system.

PMID- 7634794
TI  - Reading patch tests on day 7.

PMID- 7634795
TI  - Contact leukoderma secondary to para-phenylenediamine.

PMID- 7634796
TI  - Allergic contact dermatitis from orthopaedic devices.

PMID- 7634797
TI  - Airborne contact dermatitis from atranorin.

PMID- 7634799
TI  - Sepsis and controlled clinical trials: the odyssey continues.

PMID- 7634798
TI  - Allergic contact dermatitis from minoxidil.

PMID- 7634800
TI  - Results of the Multidisciplinary Critical Care Knowledge Assessment Program,
      1995.

PMID- 7634801
TI  - Contribution of tumor necrosis factor-alpha to pulmonary cytokine expression and
      lung injury after hemorrhage and resuscitation.
AB  - OBJECTIVE: To examine the role of tumor necrosis factor-alpha (TNF-alpha) in
      producing acute inflammatory lung injury after hemorrhage and resuscitation.
      DESIGN: Prospective, controlled animal study. SETTING: Research laboratory.
      SUBJECTS: Male BALB/c mice. INTERVENTIONS: Treatment with rat antimouse
      monoclonal anti-TNF-alpha antibodies or control rat immunoglobulin G 1 hr after
      30% blood volume hemorrhage and resuscitation. MEASUREMENTS AND MAIN RESULTS:
      Therapy with monoclonal anti-TNF-alpha antibodies prevented the posthemorrhage
      increases in pulmonary TNF-alpha and interferon-gamma protein levels that
      normally occur after blood loss. Administration of monoclonal anti-TNF-alpha
      antibodies also diminished the increases in interleukin-1 beta, interleukin-6,
      and interleukin-10 mRNA, but not the increases in TNF-alpha and interferon-gamma
      mRNA, which are found in the lungs following hemorrhage. In addition, therapy
      with monoclonal anti-TNF-alpha antibodies was associated with significant
      improvement in the histologic parameters of posthemorrhage lung injury,
      particularly intra-alveolar hemorrhage and pulmonary vascular congestion.
      CONCLUSIONS: These results indicate that TNF-alpha has an important role in the
      development of acute inflammatory lung injury after blood loss. Blockade of TNF
      alpha with monoclonal antibodies significantly reduces hemorrhage-induced lung
      injury.

PMID- 7634802
TI  - A comparison of severity of illness scoring systems for intensive care unit
      patients: results of a multicenter, multinational study. The European/North
      American Severity Study Group.
AB  - OBJECTIVE: To compare the performance of three severity of illness scoring
      systems used commonly for intensive care unit (ICU) patients in a large
      international data set. The systems analyzed were versions II and III of the
      Acute Physiology and Chronic Health Evaluation (APACHE) system, versions I and II
      of the Simplified Acute Physiology Score (SAPS), and versions I and II of the
      Mortality Probability Model (MPM), computed at admission and after 24 hrs in the
      ICU. DESIGN: A multicenter, multinational cohort study. SETTING: One hundred
      thirty-seven ICUs in 12 European and North American countries. PATIENTS: During a
      3-month period, 14,745 patients were consecutively admitted to 137 ICUs enrolled
      in the study. INTERVENTIONS: Collection of information necessary to compute the
      APACHE II and APACHE III scores, SAPS I and SAPS II, and MPM I and MPM II scores.
      Patients were followed until hospital discharges. Statistical comparison,
      including indices of calibration (goodness-of-fit) and discrimination (area under
      the receiver operating characteristic curve). MEASUREMENTS AND MAIN RESULTS:
      Despite having acceptable receiver operating characteristic areas, the older
      versions of the systems analyzed (APACHE II, SAPS, and MPM I computed at
      admission-MPM I computed after 24 hrs in the ICU) demonstrated poor calibration
      for the whole database. The new versions of the systems (SAPS II and MPM II) were
      superior to their older counterparts. This superiority is reflected by larger
      receiver operating characteristic areas and better fit. The APACHE III system
      improved its receiver operating characteristic area compared with the APACHE II
      system, which showed the best fit of the old systems analyzed. CONCLUSIONS: The
      new versions of the severity systems analyzed (APACHE III, SAPS II, MPM II)
      perform better than their older counterparts (APACHE II, SAPS I, and MPM I).
      APACHE II, SAPS II, and MPM II show good discrimination and calibration in this
      international database.

PMID- 7634803
TI  - A comparison of intensive care unit utilization in Alberta and western
      Massachusetts.
AB  - OBJECTIVE: To analyze differences in intensive care unit (ICU) utilization
      between a Canadian province and a U.S. area. DESIGN: Retrospective data analysis
      of hospital discharge data and existing data from an international study of
      severity of illness in ICU patients. SETTING: Administrative data for the
      province of Alberta and the four counties of western Massachusetts for the years
      1990 to 1991 were used. Detailed data on consecutive ICU admissions from two
      Alberta hospitals, one western Massachusetts hospital, and 24 other U.S.
      hospitals for 3 months in 1991 were used. MEASUREMENTS AND MAIN RESULTS: ICU use
      and hospital mortality rates were compared for 50,030 hospital admissions divided
      into 11 patient groups. ICU days per million population were two to three times
      as great in western Massachusetts as in Alberta. The primary reason was higher
      ICU incidence (percent of hospitalized patients treated in the ICU) rather than a
      difference in hospital admission rate or length of ICU stay. ICU incidence in
      western Massachusetts was significantly higher in ten of 11 patient groups--for
      the coronary bypass surgery group, there was no difference. The hospital
      mortality rate in western Massachusetts was similar to, or higher than, the
      mortality rate in Alberta. In Alberta, a much higher proportion of ICU patients
      received mechanical ventilation. For elective surgery patients, the ICU severity
      of illness was lower in western Massachusetts and in other U.S. hospitals than in
      Alberta. CONCLUSIONS: Western Massachusetts hospitalized patients are more likely
      to be treated in an ICU than are similar patients in Alberta. There is no
      evidence that the greater ICU utilization in western Massachusetts led to a lower
      hospital mortality rate.

PMID- 7634804
TI  - Concentrations of prolactin and prostaglandins during and after cardiopulmonary
      resuscitation.
AB  - OBJECTIVES: To assess differences in plasma prolactin and prostaglandin
      concentrations in resuscitated and nonresuscitated patients during
      cardiopulmonary resuscitation (CPR), and to compare changes of prostaglandin and
      prolactin concentrations with hemodynamic variables in the immediate
      postresuscitation phase. DESIGN: Prospective, descriptive study. SETTING:
      Emergency medical service at a university hospital. PATIENTS: Twenty-nine
      patients ranging in age from 39 to 87 yrs with out-of-hospital cardiac arrest.
      INTERVENTIONS: Venous blood samples were taken during CPR and at 5, 15, 30, and
      60 mins after restoration of spontaneous circulation in order to measure plasma
      concentrations of prolactin, prostaglandin F2 alpha, 15-keto-13,14-dihydro
      prostaglandin F2 alpha, 6-keto-prostaglandin F1 alpha, and thromboxane B2 by
      immunoassay. Heart rate and blood pressure were measured at 5, 15, 30, and 60
      mins after restoration of spontaneous circulation. MEASUREMENTS AND MAIN RESULTS:
      In 15 patients, restoration of spontaneous circulation was achieved; in the
      remaining 14 patients, successful resuscitation was not possible. During CPR, the
      mean plasma prolactin, prostaglandin F2 alpha, 15-keto-13,14-dihydro
      prostaglandin F2 alpha, 6-keto-prostaglandin F1 alpha, and thromboxane B2
      concentrations were 95.9 +/- 13.6 micrograms/L, 357 +/- 61 ng/L, 228 +/- 28 ng/L,
      277 +/- 66 ng/L, and 375 +/- 78 ng/L, respectively, in resuscitated patients, and
      23.9 +/- 5.6 micrograms/L (p = .0001), 192 +/- 22 ng/L (p = .005), 202 +/- 31
      ng/L (p = .528), 221 +/- 40 ng/L (p = .713), and 344 +/- 77 ng/L (p = .780),
      respectively, in nonresuscitated patients. At 60 mins after restoration of
      spontaneous circulation, the mean plasma prolactin, prostaglandin F2 alpha, 15
      keto-13,14-dihydro-prostaglandin F2 alpha, 6-keto-prostaglandin F1 alpha, and
      thromboxane B2 concentrations were 50.1 +/- 9.5 micrograms/L, 306 +/- 42 ng/L,
      503 +/- 87 ng/L, 278 +/- 55 ng/L, and 355 +/- 30 ng/L, respectively. Mean values
      of systolic arterial blood pressure were 114 +/- 12 mm Hg at 30 mins and 123 +/-
      18 mm Hg at 60 mins. No significant correlations were found between hemodynamic
      values and plasma concentrations of prolactin or prostaglandins. CONCLUSIONS:
      Prolactin and prostaglandin concentrations were increased during cardiac arrest
      and CPR. Successful initial resuscitation was associated with increased prolactin
      and prostaglandin F2 alpha concentrations during CPR. Decreased concentrations in
      non-resuscitated patients may have been a result of exhaustion of the
      neuroendocrine and eicosanoid systems, or may be due to differences in
      bioavailability at the site of blood sampling based upon differences in
      hemodynamics.

PMID- 7634805
TI  - Effect of erythromycin on gastric motility in mechanically ventilated critically
      ill patients: a double-blind, randomized, placebo-controlled study.
AB  - OBJECTIVE: To document the action of erythromycin on gastric emptying and
      motility in mechanically ventilated patients. DESIGN: Crossover, double-blind,
      randomized, placebo-controlled study. SETTING: General intensive care unit in a
      university hospital. PATIENTS: Ten patients, mechanically ventilated, in a stable
      hemodynamic condition. INTERVENTIONS: Erythromycin (200 mg i.v. over 30 mins) and
      placebo were infused at mid-morning, on two consecutive days, in a random order.
      Pressure changes in the gastric antrum were recorded by means of a multi-lumen
      manometric tube (perfused catheter technique) over a period of 300 mins,
      beginning with the institution of the erythromycin or placebo infusion. Gastric
      emptying was simultaneously assessed by the kinetics of the absorption of
      acetaminophen delivered into the stomach (1 g with 20 mL of water) immediately
      before the infusion. MEASUREMENTS AND MAIN RESULTS: Motility was quantified by
      determining the number of contractions, the amplitude of contractions, and the
      Motility Index (Motility Index = natural logarithm [sum of amplitude x number of
      contractions] + 1). Comparison between placebo and erythromycin was made for the
      first hour after the infusion and for the whole recording session. The maximal
      acetaminophen concentration, the time to reach the peak acetaminophen
      concentration, and the area under the concentration-time curve at 60 mins were
      obtained from serial determinations of plasma acetaminophen concentrations.
      Compared with placebo, the mean number of contractions (104 +/- 34 vs. 5 +/- 8; p
      = .003), the mean amplitude of contractions (52 +/- 16 vs. 20 +/- 17 mm Hg; p =
      .005), and the Motility Index (13.06 +/- 0.95 vs. 4.45 +/- 3.54; p = .004) were
      significantly increased during the first hour after erythromycin infusion
      compared with placebo. Number of contractions (p = .017) and Motility Index (p <
      .001) after erythromycin infusion remained significantly higher when values
      throughout the whole recording session were considered. The following data were
      noted after erythromycin was infused: a) the time to reach the peak acetaminophen
      concentration was shorter (32 +/- 8 vs. 171 +/- 93 mins; p = .007); b) the
      maximal acetaminophen concentration was higher (22.09 +/- 6.23 vs. 5.38 +/- 3.80
      micrograms/mL; p = .007); and c) the area under the concentration-time curve at
      60 mins increased markedly (730 +/- 269 vs. 72 +/- 42 micrograms/min/mL; p =
      .002) as compared with placebo. CONCLUSION: In mechanically ventilated patients,
      intravenous erythromycin (200 mg over 30 mins) increases indices of antral
      motility and accelerates gastric emptying as assessed by the kinetics of
      acetaminophen absorption.

PMID- 7634806
TI  - Methylene blue increases myocardial function in septic shock.
AB  - OBJECTIVE: To study whether the circulatory changes of human septic shock are
      mediated in part by nitric oxide. DESIGN: Open-label, nonrandomized clinical
      trial on the effects of methylene blue, an inhibitor of nitric oxide action.
      SETTING: Intensive care unit of a teaching hospital. PATIENTS: Nine consecutive
      patients with documented septic shock and a pulmonary artery catheter in place,
      after initial resuscitation with fluids, sympathomimetics, and mechanical
      ventilation. INTERVENTIONS: Hemodynamic and metabolic variables were measured
      before and then 15, 30, 60, and 120 mins after the start of a 20-min infusion of
      2 mg/kg of methylene blue. MEASUREMENTS AND MAIN RESULTS: Patients had a
      hyperdynamic circulation, and methylene blue increased (p < .01) mean arterial
      pressure from 84 +/- 18 to 109 +/- 31 mm Hg and cardiac index from 4.7 +/- 0.9 to
      5.6 +/- 1.2 L/min/m2, before and 30 mins after starting the methylene blue
      infusion, respectively. Cardiac filling pressures did not change. In the same
      time interval, the subnormal systemic vascular resistance index increased (p =
      .09) and arterial compliance decreased (p < .05). Oxygen delivery and oxygen
      uptake increased (p < .05) from 714 +/- 188 to 865 +/- 250 mL/min/m2 and from 160
      +/- 39 to 186 +/- 44 mL/min/m2, respectively. Except for heart rate, which
      increased by 11 +/- 8 beats/min (p < .01), variables returned to baseline values
      at time = 120 mins. CONCLUSIONS: After initial resuscitation from human septic
      shock, a single dose of methylene blue transiently increases mean arterial
      pressure and oxygen uptake, associated with a decrease in arterial compliance and
      increases in myocardial function and oxygen delivery. Hence, nitric oxide may be
      a mediator of the circulatory changes of human septic shock.

PMID- 7634807
TI  - Induction of heat shock gene expression in colonic epithelial cells after
      incubation with Escherichia coli or endotoxin.
AB  - OBJECTIVE: The universal cellular response to stress is the expression of a
      family of genes known as heat shock or stress proteins. We investigated whether
      bacteria or bacterial products (endotoxin) can induce heat shock protein
      expression in human enterocytes. DESIGN: Controlled, in vitro study. SETTING:
      Cell culture laboratory. SUBJECTS: Human Caco-2 enterocyte cell line.
      MEASUREMENTS AND MAIN RESULTS: Incubation of confluent monolayers of Caco-2 cells
      with Escherichia coli C25 (1 x 10(9) bacteria/mL) for 1 hr at 37 degrees C was
      found to induce the expression of the 72-kilodalton molecular weight heat shock
      protein gene (heat shock protein-72), the major inducible form of the 70
      kilodalton molecular weight heat shock protein family of stress proteins, as
      detected by Western blot analysis. The level of heat shock protein-72 induction
      after incubation with E. coli was similar to the response of Caco-2 cells to heat
      shock at 43 degrees C for 1 hr. The induction of heat shock protein-72 gene
      expression by E. coli was not purely due to the process of phagocytosis, since
      incubation of Caco-2 cells with latex beads (1 micron) failed to induce heat
      shock gene expression. To elucidate the possible mechanism of heat shock protein
      72 induction mediated by bacteria, Caco-2 cells were incubated with E. coli
      endotoxin (200 micrograms/mL) for 1 hr at 37 degrees C. Such treatment was also
      found to induce the synthesis of heat shock protein-72. CONCLUSIONS: These
      results demonstrate that bacteria and/or bacterial products induce the heat shock
      gene expression in Caco-2 cells. Since intestinal epithelial cells are constantly
      in contact with bacteria and bacterial products, we speculate that the heat shock
      gene expression may be part of the natural mechanism of protection for these
      cells in the potentially harmful environment that may be present in the
      intestinal tract.

PMID- 7634809
TI  - Effect of volume support, antibiotic therapy, and monoclonal antiendotoxin
      antibodies on mortality rate and blood concentrations of endothelin and other
      mediators in fulminant intra-abdominal sepsis in rats.
AB  - OBJECTIVE: To study the therapeutic effects of volume support, antibiotics, and a
      monoclonal antiendotoxin antibody on the mortality rate and blood concentrations
      of endothelin and other mediators in fulminant intra-abdominal sepsis in rats.
      DESIGN: Prospective, randomized, controlled trial. SETTING: Research laboratory
      in a university hospital. SUBJECTS: Adult male Wistar rats. INTERVENTIONS:
      Fulminant polymicrobial intra-abdominal sepsis was induced by a 4-mm cecal
      perforation. Treatment was performed with saline volume support, the antibiotic
      imipenem/cilastatin, and the monoclonal antiendotoxin antibody E5, both as
      monotherapy and as a combined regimen. Mortality rates were recorded and
      concentrations of bacteria, endotoxin, tumor necrosis factor (TNF), big
      endothelin, and endothelin-1 (21 amino acids) in blood were determined.
      MEASUREMENTS AND MAIN RESULTS: Substantial increases in circulating big
      endothelin and endothelin-1 concentrations were observed during sepsis. The
      combination of volume support with antibiotics reduced the mortality rate, but
      neither as monotherapy nor as a combined regimen did this intervention modify
      plasma endothelin-1 concentrations. This finding suggests that hypovolemia and
      bacteria per se are not important stimuli for endothelin synthesis and a high
      plasma level of endothelin-1 does not necessarily predict poor outcome in sepsis.
      The inactive big endothelin is enzymatically cleaved, leaving the biologically
      active 21-residue endothelin-1. Intervention with E5 substantially reduced the
      mortality rate and concentrations of endotoxin, TNF, and plasma endothelin-1,
      while big endothelin and total endothelin immunoreactivity did not decrease. This
      finding indicates a suppressed conversion of big endothelin to endothelin-1 after
      E5 treatment. Because E5 has no direct effect on endothelin metabolism, E5
      probably reduces the synthesis of endothelin-1 by suppressing the endothelin
      activators endotoxin and TNF. A triple combination of volume support,
      imipenem/cilastatin, and E5 was the only regimen that reduced all of the end
      points: mortality rate, hemoconcentration, bacteria, endotoxin, TNF, and
      endothelin-1. CONCLUSIONS: The concentration of plasma endothelin was increased
      during fulminant intra-abdominal sepsis in rats. Combining volume support with
      antibiotic therapy reduced the mortality rate, but did not modify concentrations
      of plasma endothelin-1. The monoclonal antiendotoxin antibody E5 reduced the
      mortality rate and concentrations of endotoxin, TNF, and endothelin-1, but not
      big endothelin. This finding indicates that E5 therapy inhibits the conversion of
      big endothelin to 21-residue endothelin-1.

PMID- 7634808
TI  - Soluble tumor necrosis factor receptors reduce bowel ischemia-induced lung
      permeability and neutrophil sequestration.
AB  - OBJECTIVES: To evaluate the possible role of tumor necrosis factor (TNF) in the
      development of lung injury after bowel ischemia, and the ability of TNF-soluble
      receptors to negate TNF toxicity, using a rat small bowel ischemia and
      reperfusion model. DESIGN: Prospective, randomized, controlled laboratory study.
      SETTING: Research laboratory. SUBJECTS: Forty adult male Sprague-Dawley rats
      weighing approximately 300 g. INTERVENTIONS: The rats were divided equally into
      four groups: a) ischemia and reperfusion alone; b) those animals receiving TNF
      antibodies (1 mL) before reperfusion; and c) those animals receiving 200
      micrograms of human recombinant TNF soluble receptors. These 30 anesthetized rats
      underwent 60 mins of superior mesenteric artery occlusion per 4 hrs of
      reperfusion. The remaining ten animals were sham operated (laparotomy), serving
      as controls. Lung permeability was measured using bovine serum albumin labeled
      with 125I, and organ injury was assessed histologically. MEASUREMENTS AND MAIN
      RESULTS: Thirty and 60 mins after declamping and reperfusion, plasma TNF
      concentrations increased to 830 +/- 66 and 173 +/- 56 pg/mL, respectively,
      compared with 10 pg/mL before ischemia (p < .001). In sham-operated control rats,
      TNF concentrations did not increase from baseline concentrations. Four hours
      after reperfusion, sequestration of neutrophils in the pulmonary microcirculation
      was noted (319 +/- 60 vs. 84 +/- 13 neutrophils/10 high-power fields in sham
      operated rats [p < .04]). Pulmonary microvascular leak also occurred, as measured
      by translocation of radiolabeled albumin into the bronchoalveolar space and
      expressed as the ratio of bronchoalveolar lavage to blood concentrations. This
      ratio was 5.3 +/- 0.8 in ischemic control animals compared with 1.1 +/- 0.3 in
      sham animals (p < .03). Treatment with antibodies to TNF before reperfusion
      attenuated the pulmonary injury (75 +/- 6 neutrophils/10 high-power fields,
      permeability index 1.6 +/- 0.1) less than in ischemic controls (p < .005). A
      similar protection was achieved with soluble TNF receptors, which prevented bowel
      ischemia-induced lung neutrophil sequestration (117 +/- 35 neutrophils/10 high
      power fields, pulmonary vascular leak ratio of 2.3 +/- 0.1, p < .05).
      CONCLUSIONS: The results of this study show that ischemia and subsequent
      reperfusion of the intestine in rats produce lung injury. This injury is
      mediated, at least in part, by TNF. Soluble TNF receptors are an effective tool
      in preventing lung TNF injury after intestinal ischemia.

PMID- 7634810
TI  - Cerebral hemodynamics and distribution of left ventricular output during
      inhalation of nitric oxide.
AB  - OBJECTIVES: Inhaled nitric oxide is being utilized as a selective pulmonary
      vasodilator in the treatment of persistent pulmonary hypertension of the newborn.
      However, the effects of inhaled nitric oxide on cerebral hemodynamics and
      distribution of left ventricular output in newborn subjects have not been
      studied. This study was designed to measure quantitatively the effect of inhaled
      nitric oxide on the distribution of left ventricular output and on cerebral
      hemodynamics in a perinatal animal model. DESIGN: Prospective, controlled,
      experimental study. SETTING: Research laboratory. SUBJECTS: Eight fetal sheep.
      INTERVENTIONS: Each animal was exposed to three separate study periods: a)
      mechanical ventilation with low FIO2 (maintaining fetal levels of PaO2); b)
      inhalation of nitric oxide (20 parts per million) during mechanical ventilation
      and low FIO2; and c) mechanical ventilation with an FIO2 of 1.0. MEASUREMENTS AND
      MAIN RESULTS: Left ventricular output and cerebral blood flow were measured with
      radiolabeled microspheres. Cerebral oxygen delivery and consumption variables
      were calculated using measurements of arterial and cerebral venous (sagittal
      sinus) oxygen content. Total left ventricular output did not differ among the
      three treatment groups: 235 +/- 16 mL/min/kg with hypoxic ventilation; 283 +/- 13
      mL/min/kg with nitric oxide inhalation; and 242 +/- 17 mL/min/kg with an FIO2 of
      1.0. Lung blood flow increased 2.7-fold with inhaled nitric oxide and 1.6-fold
      during mechanical ventilation with an FIO2 of 1.0. With a left ventricle
      microsphere injection, increased lung blood flow is indicative of increased
      systemic-to-pulmonary shunt across the ductus arteriosus. Whole brain blood flow
      did not differ between the three groups: 49.6 +/- 6.7 mL/min/100 g with hypoxic
      ventilation; 46.4 +/- 7.4 mL/min/100 g with nitric oxide inhalation; and 36.4 +/-
      3.8 mL/min/100 g with an FIO2 of 1.0. Cerebral oxygen delivery increased during
      inhalation of an FIO2 of 1.0 when compared with nitric oxide inhalation (p <
      .007); fractional extraction of oxygen decreased (p < .004 compared with hypoxic
      ventilation, p < .0005 compared with nitric oxide inhalation). Cerebral oxygen
      consumption did not differ between the three groups (1.11 +/- 0.12
      microns/min/100 g with hypoxic ventilation, 0.95 +/- 0.12 microns/min/100 g with
      nitric oxide inhalation, and 0.96 +/- 0.08 microns/min/100 g with an FIO2 of
      1.0). CONCLUSION: Acute pulmonary vasodilation caused by inhalation of nitric
      oxide does not change left ventricular output, cerebral blood flow, or cerebral
      oxygen consumption, despite an increased systemic-to-pulmonary shunt across the
      ductus arteriosus.

PMID- 7634811
TI  - Hyperbaric oxygen after global cerebral ischemia in rabbits does not promote
      brain lipid peroxidation.
AB  - OBJECTIVE: To determine whether hyperbaric oxygen administered immediately after
      global cerebral ischemia increases free radical generation and lipid peroxidation
      in the brain or alters neurophysiologic recovery. DESIGN: Prospective,
      randomized, controlled trial. SETTING: Animal research laboratory. SUBJECTS:
      Adult male New Zealand white rabbits. INTERVENTIONS: Anesthetized rabbits were
      subjected to 10 mins of global cerebral ischemia by infusing a mock cerebrospinal
      fluid into the subarachnoid space and increasing intracranial pressure equal to
      mean arterial pressure. Immediately upon reperfusion, one group of rabbits (n =
      9) was treated with hyperbaric oxygen at 2.8 atmospheres absolute for 75 mins
      while the control group (n = 9) breathed room air for an equivalent period of
      time. At the end of the reperfusion period, oxyradical brain damage was
      determined by measuring brain levels of oxidized and total glutathione and free
      malondialdehyde. Neurophysiologic brain injury was assessed with cortical
      somatosensory evoked potentials. MEASUREMENTS AND MAIN RESULTS: Both oxidized
      glutathione and the ratio of oxidized glutathione to reduced glutathione (total
      minus oxidized) were higher (p < .05) in the hyperbaric oxygen group, indicating
      that hyperbaric oxygen increased free radical generation. Nonetheless, brain
      malondialdehyde content, an index of lipid peroxidation, was similar (p > .05) in
      the two groups. Cortical somatosensory evoked potential recovery at the end of
      reperfusion was 50% higher (p < .05) in the hyperbaric oxygen-treated animals
      compared with controls. CONCLUSIONS: Treatment with hyperbaric oxygen after
      ischemia increased the amount of oxygen free radicals in the brain. However, this
      increase in free radical generation was not associated with an increase in lipid
      peroxidation or a reduction in neurophysiologic recovery when measured after 75
      mins of recirculation. These results suggest that hyperbaric oxygen administered
      immediately after global ischemia does not promote early brain injury.

PMID- 7634813
TI  - Cerebral blood flow, vascular resistance, and oxygen metabolism in acute brain
      trauma: redefining the role of cerebral perfusion pressure?
AB  - OBJECTIVES: To evaluate normal or high cerebral perfusion pressure in relation to
      cerebral blood flow and oxygen metabolism, as well as other multivariate cerebral
      hemodynamic and metabolic interrelationships, in acute brain trauma in humans.
      DESIGN: Prospective, observational study. SETTING: Neuroscience intensive care
      unit of a university hospital. PATIENTS: Adults (n = 66) with severe acute brain
      trauma (Glasgow Coma Scale scores from 4 to 8), undergoing multivariate
      physiologic studies involving cerebral perfusion pressure, cerebral blood flow,
      cerebral metabolic rate of oxygen consumption, total hemoglobin content, arterio
      jugular oxygen content difference, and cerebral vascular resistance, along with
      other routine procedures. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS:
      Statistical analysis did not demonstrate any correlation between cerebral
      perfusion pressure and cerebral blood flow, between cerebral perfusion pressure
      and arterio-jugular oxygen content difference, and between cerebral perfusion
      pressure and cerebral metabolic rate of oxygen consumption, over a broad spectrum
      of perfusion pressures ranging from 60 to 130 mm Hg. In contrast, a significant
      negative correlation was found between cerebral vascular resistance and cerebral
      blood flow, where higher values of cerebral vascular resistance were associated
      with lower blood flow levels, and vice versa. CONCLUSIONS: In severe acute brain
      trauma, cerebral hemodynamic and oxygen metabolic variables are not necessarily
      correlated with normal or even high levels of cerebral perfusion pressure. Under
      these circumstances, cerebral vascular resistance (not perfusion pressure) is
      more closely correlated with different patterns of cerebral blood flow and
      metabolism.

PMID- 7634812
TI  - Aspiration-induced lung injury: role of complement.
AB  - OBJECTIVES: To examine the role of complement in the development of acid
      aspiration-induced lung injury in the rat. It was postulated that inhibition or
      depletion of complement attenuates aspiration-induced lung injury. DESIGN:
      Controlled animal trial. SETTING: Animal Laboratory, Jefferson Medical College,
      Philadelphia, PA. SUBJECTS: Anesthetized rats. INTERVENTIONS: Aspiration was
      induced by the intratracheal administration of 0.2 mL of 0.1 N hydrochloric acid
      (n = 7) and lung injury was evaluated by determining water content,
      myeloperoxidase activity, protein concentration, and leukocyte count in
      bronchoalveolar lavage fluid. Muscle PO2 was directly measured using a thin-film
      chamber oxygen sensor and serum tumor necrosis factor-alpha was assayed by enzyme
      linked immunosorbent assay. The effect of complement inhibition by recombinant
      human soluble complement receptor type 1 (n = 8) or complement depletion by cobra
      venom factor (n = 7) on lung injury was evaluated. MEASUREMENTS AND MAIN RESULTS:
      Acid aspiration induced pulmonary leukosequestration, edema, and a microvascular
      permeability defect, along with tissue hypoxia. Pretreatment with soluble
      complement receptor type 1 (complement inhibition) or cobra venom factor
      (complement depletion) significantly reduced lung edema (-61 +/- 7%; p < .05),
      eliminated protein accumulation in bronchoalveolar lavage fluid (p < .01), and
      improved (p < .05) tissue oxygenation. In contrast, there was no effect of
      soluble complement receptor type 1 or of cobra venom factor on
      leukosequestration. CONCLUSIONS: Acid aspiration induces lung injury through a
      complement-dependent mechanism that leads to microvascular permeability defects.
      Therefore, the possibility that complement inhibitors may have a salutary effect
      in humans with aspiration-induced lung injury should be investigated.

PMID- 7634814
TI  - Pharmacokinetics of phenytoin in children with acute neurotrauma.
AB  - OBJECTIVE: To determine the pharmacokinetics of intravenous phenytoin in
      critically ill infants and children with acute neurologic injury. DESIGN: A
      prospective, descriptive study. SETTING: A pediatric intensive care unit.
      PATIENTS: Sixteen children, 0.5 to 16 yrs of age (mean 7.6), with various types
      of acute neurologic injuries, receiving intravenous phenytoin therapy.
      INTERVENTIONS: Blood samples were collected to measure total and free phenytoin
      concentrations in plasma. A 24-hr urine collection was made to determine the
      concentrations of the major metabolite of phenytoin. MEASUREMENTS AND MAIN
      RESULTS: In 12 children who survived the acute illness, a lower-than-predicted
      Michaelis-Menten constant (Km) and higher-than-predicted maximum rate of
      metabolism (Vmax) were observed. Initial free phenytoin fractions ranged between
      0.08 and 0.15. In the eight patients who had additional free fractions measured,
      six patients demonstrated an increase (9.1% to 34% increase) in free fraction,
      while two patients demonstrated a decrease (1.8% and 19.8% decrease) in free
      fraction. The ratio of amount of phenytoin to phenytoin plus 5-(p-hydroxyphenyl)
      5-phenylhydantoin excreted in the urine in a 24-hr urine collection demonstrated
      a wide inter-patient variability. There was no correlation in the difference
      between the predicted and calculated Km and Vmax values and Glasgow Coma Score,
      circulating albumin concentration, or concomitant medications. CONCLUSION: Based
      on the average Km and Vmax values of the children enrolled in our study, it
      appears that children with neurologic injury between the ages of 0.5 and 9 yrs
      may require dosages of at least 8 to 10 mg/kg/day, and children aged 10 to 16 yrs
      may require 6 to 8 mg/kg/day to attain therapeutic phenytoin concentrations.

PMID- 7634815
TI  - Physician burnout in pediatric critical care medicine.
AB  - OBJECTIVES: To determine the prevalence of, and factors associated with, burnout
      among pediatric intensivists across a variety of practice settings. DESIGN: A
      population-based survey, using a mailed questionnaire that included a previously
      validated Burnout Scale. SETTING: Private and academic pediatric critical care
      practices. PARTICIPANTS: Respondents from among all members of the Pediatric
      Section of the Society of Critical Care Medicine and all physicians certified in
      pediatric critical care medicine by the American Board of Pediatrics.
      MEASUREMENTS AND MAIN RESULTS: The questionnaire consisted of demographic items,
      variables noted in the literature as being associated with burnout (e.g., the
      individual's perception of how others valued their work, and the use of
      preventive measures such as regular exercise to relieve stress), and a validated
      Burnout Scale. The questionnaire also included questions pertaining to past
      training, practice of other primary specialties or subspecialties, practice
      settings, admission responsibilities, actual and preferred practice activities,
      total work effort, academic activities, and causes of stress at work. The Burnout
      Scale of Pines and Aronson is a self-diagnosis instrument, consisting of 21
      questions using a 7-point frequency scale. The total Burnout Score represents an
      average of the scores for the individual components. Scores of < or = 3 in our
      study were classified as "not burned out." Scores of > 3 and < or = 4 were
      classified as "at risk." Scores of > 4 were classified as "burned out." A total
      of 883 questionnaires were mailed; 474 (56%) were respondent returns and 35
      questionnaires could not be delivered. Primary analyses focused on the 389
      respondent attending physicians presently practicing pediatric critical care
      medicine at the time of the survey. The average Burnout Score of these attending
      physicians was 3.1 +/- 0.8; 36% were classified as being at risk for burnout, and
      14% were classified as burned out. There was no association between burnout
      status and the following work conditions: having fellows; having protected time
      for research and publications; frequency of being called at home; frequency of
      returning to the hospital when called at home; or call schedule. Respondents
      classified as burned out were significantly more likely than respondents who were
      classified as not burned out to feel that their work was not valued by others.
      Burned out respondents were less likely than respondents who were not burned out
      to give the following description: feeling very successful; feeling that their
      peers viewed them as very successful; feeling satisfied in their professional
      life; and routinely exercising or having some other outside interest.
      CONCLUSIONS: We found that a high degree of burnout exists in pediatric critical
      care medicine, with 50% of pediatric intensivists at risk or burned out. Overall,
      there was no association between Burnout Scores and training, practice
      specialties, or practice settings, nor was there an association with aspects of
      practice that are physically taxing. However, perceptions about the value of
      their work and feelings of success and satisfaction were highly associated with
      those respondents classified as burned out. Routine exercise (a strategy used by
      some for stress reduction) was associated with lower Burnout Scores. Further
      studies are necessary to evaluate the trends that we have reported and to
      identify causal factors.

PMID- 7634816
TI  - Corticosteroid treatment for sepsis: a critical appraisal and meta-analysis of
      the literature.
AB  - OBJECTIVE: To determine the effect of corticosteroid therapy on morbidity and
      mortality in patients with sepsis. DATA SOURCES: We searched for published and
      unpublished research using MEDLINE, EMBASE, and the Science Citation Index,
      manual searching of Index Medicus, citation review of relevant primary and review
      articles, personal files, and contact with primary investigators. STUDY
      SELECTION: From a pool of 124 potentially relevant articles, duplicate
      independent review identified nine relevant, randomized, controlled trials of
      corticosteroid therapy in sepsis and septic shock among critically ill adults.
      DATA EXTRACTION: In duplicate, independently, we abstracted key data on
      population, intervention, outcome, and methodologic quality of the randomized
      controlled trials. DATA SYNTHESIS: Corticosteroids appear to increase mortality
      in patients with overwhelming infection (relative risk 1.13, 95% confidence
      interval 0.99 to 1.29), and have no beneficial effect in the subgroup of patients
      with septic shock (relative risk 1.07, 95% confidence interval 0.91 to 1.26).
      Studies with the highest methodologic quality scores also suggest a trend toward
      increased mortality overall (relative risk 1.10, 95% confidence interval 0.94 to
      1.29). A similar trend was observed for patients with septic shock (relative risk
      1.12, 95% confidence interval 0.95 to 1.32). No difference in secondary infection
      rates was demonstrated in corticosteroid-treated patients with sepsis or septic
      shock. However, there was a trend toward increased mortality from secondary
      infections in patients receiving corticosteroids (relative risk 1.70, 95%
      confidence interval 0.70 to 4.12). The occurrence rate of gastrointestinal
      bleeding was increased slightly in the treatment group (relative risk 1.17, 95%
      confidence interval 0.79 to 1.73). CONCLUSIONS: Current evidence provides no
      support for the use of corticosteroids in patients with sepsis or septic shock,
      and suggests that their use may be harmful. These trials underscore the need for
      future methodologically rigorous trials evaluating new immune-modulating
      therapies in well-defined critically ill patients with overwhelming infection.

PMID- 7634817
TI  - Atracurium and status epilepticus?

PMID- 7634818
TI  - High-frequency ventilation versus conventional mechanical ventilation in
      pediatric respiratory failure.

PMID- 7634819
TI  - Mechanical ventilation in pediatric respiratory failure.

PMID- 7634820
TI  - Tension pneumothorax in newborn piglets.

PMID- 7634821
TI  - Critically ill obstetrical patients: outcome and predictability.

PMID- 7634822
TI  - Chest wall tumors.

PMID- 7634823
TI  - S-nitrosothiols and the bioregulatory actions of nitrogen oxides through
      reactions with thiol groups.
AB  - The reactivity of selected RS-NOs has led to the misconception that these
      compounds are uniformly unstable under physiological conditions. Moreover,
      current evidence supports the notion that biological responses elicited by RS-NOs
      may result from either liberation of nitric oxide or from NO group transfer
      chemistry involving either NO+ or NO-. Some evidence suggests that such reactions
      may be enzymatically controlled. The data supporting the potential biological
      relevance of RS-NOs include: (1) evidence that these compounds form under
      physiological conditions; (2) their identification in insects, lower mammals, and
      several human biological systems; and (3) findings that RS-NOs possess a wide
      range of biological activities, including antimicrobial effects, vasodilation,
      platelet inhibition, bronchodilation and inhibition of intestinal motility, while
      being relatively resistant to reactions with O2 and O2- associated with NO.
      toxicity. It is further noteworthy that biological activity of RS-NO is often not
      related to the propensity to liberate NO., and these adducts are generally more
      potent and selective in their action than NO. itself (Stamler et al. 1989; Cooke
      et al. 1990; Rockett et al. 1991; Jansen et al. 1991; Lipton et al. 1993). The
      data presented here support the idea that RS-NO may be involved in stabilizing
      nitric oxide-like bioactivity, in transporting and targeting the NO group to
      specific (thioregulatory) effector sites, in mitigating the cytotoxic effects of
      nitric oxide that result from reaction with oxygen species, and may serve to
      regulate protein function in a posttranslational modification akin, perhaps, to
      phosphorylation. The recently demonstrated NO group transfer reactions to plasma
      membrane proteins containing reactive sulfhydryls (Lipton et al. 1993; Stamler
      1994) also raises the possibility of signal transduction initiated through more
      traditional "agonist-receptor" mediated pathways.

PMID- 7634824
TI  - Diffusible messengers and intercellular signaling: locally distributed synaptic
      potentiation in the hippocampus.

PMID- 7634825
TI  - The role of peroxynitrite in nitric oxide-mediated toxicity.

PMID- 7634826
TI  - Bcl-2 and Bcl-2-related proteins in apoptosis regulation.
AB  - In this review we have discussed the importance of Bcl-2 and related proteins in
      the regulation of apoptotic cell death in mammalian systems. It is clear that Bcl
      2 plays a critical role in controlling many forms of PCD. Bcl-2 seems to have
      particular significance in lymphocyte development and the function of the immune
      system. We have also discussed the increasing size of the newly identified Bcl-2
      family. There are a number of Bcl-2 homologues in human, murine, avian, nematode,
      and viral systems. The evolutionary conservation of the function of the Bcl-2
      homologues, reinforces the importance of PCD in all complex organisms. Some of
      these bcl-2-like genes function as agonists and others as antagonists. Despite
      the seemingly universal importance of Bcl-2, it is unable to prevent PCD in all
      systems. In addition, we have described a role for other Bcl-2 family members in
      systems in which Bcl-2 is ineffective and supplied a potential rationale for the
      large number of genes involved in the regulation of PCD. Identification and
      functional analysis of the Bcl-2 family members reveals the complex nature of
      cell death regulation. As we begin to appreciate the significance of PCD in the
      control of development and homeostasis, its regulation at the molecular level is
      becoming better understood. Bcl-2 has long been the only known intracellular
      regulator of the PCD pathway(s), although its ability to prevent apoptosis is not
      universal. We now know that bcl-2 is only one member of an evolutionary conserved
      family of genes which display different patterns of expression as well as
      function. At least two family members, Bcl-xs and Bax, act in opposition to Bcl
      2. The discovery of these new family members, including those with Bcl-2-like
      function and antagonists, should help clear up the discrepancies seen in Bcl-2's
      ability to protect cells from PCD. In doing so, we will be able to further define
      the pathways associated with cell death signaling. The study of these family
      members, as well as the non-related genes of the PCD pathways (ced-3, ced-4, ice)
      should lead us to understanding of how cells of multicellular organisms make
      decisions to die.

PMID- 7634827
TI  - Lymphocyte death, p53, and the problem of the "undead" cell.

PMID- 7634828
TI  - Death genes in T cells.

PMID- 7634829
TI  - Molecular events in thymocyte apoptosis.

PMID- 7634830
TI  - B cell activation and apoptosis.

PMID- 7634831
TI  - Tissue transglutaminase: a candidate effector element of physiological cell
      death.

PMID- 7634832
TI  - Chronic activation of the immune system in HIV infection: contribution to T cell
      apoptosis and V beta selective T cell anergy.

PMID- 7634833
TI  - Programmed cell death and AIDS pathogenesis: significance and potential
      mechanisms.

PMID- 7634834
TI  - Programmed death of T cells in HIV infection: result of immune activation?

PMID- 7634835
TI  - Maintenance of the T lymphocyte pool by inhibition of apoptosis: a novel strategy
      of immunostimulation?

PMID- 7634836
TI  - Characterization of signals leading to clonal expansion or to cell death during
      lymphocyte B cell activation.

PMID- 7634837
TI  - Glucocorticoid-induced death of immune cells: mechanisms of action.

PMID- 7634838
TI  - Thymocyte apoptosis by glucocorticoids and cAMP.

PMID- 7634839
TI  - Regulation of apoptosis via steroid receptors.

PMID- 7634841
TI  - Contactants that produce nonimmunologic erythema or urticaria: Part I.

PMID- 7634840
TI  - Calcium and cyclosporin A in the regulation of apoptosis.

PMID- 7634843
TI  - A dermatologic diary. Portrait of a practice.

PMID- 7634842
TI  - Pyogenic granuloma.

PMID- 7634844
TI  - Botryomycosis in the acquired immunodeficiency syndrome.
AB  - Botryomycosis is a rare bacterial infection that may mimic fungal disease both
      clinically and histologically. Cutaneous botryomycosis is uncommon and usually
      appears as plaques with superficial pustules and crusts. On microscopic
      examination lesions are characterized by the presence of granules that resemble
      the sulfur granules of actinomyces with a granulomatous inflammatory response. An
      increased incidence has been reported in populations with altered immune function
      and the presentation may be atypical in patients with the acquired
      immunodeficiency syndrome. We report the successful treatment of a case of
      mucocutaneous botryomycosis in a patient with acquired immunodeficiency syndrome.
      A review of the literature is presented, with special emphasis on cutaneous
      manifestations of botryomycosis in patients with acquired immunodeficiency
      syndrome.

PMID- 7634846
TI  - Disseminated granuloma annulare in acquired immunodeficiency syndrome: case
      report and review of the literature.
AB  - The authors report the case of a 27-year-old woman who presented with
      disseminated granuloma annulare in association with acquired immunodeficiency
      syndrome. The lesions were asymptomatic, tiny, erythematous or flesh-colored
      umbilicated papules on the neck, trunk, and flexor surface of the arms and knees
      that regressed without any treatment in two months. The case reported is the
      nineteenth description of the association of granuloma annulare and acquired
      immunodeficiency syndrome but the first in a female patient. The causes and
      pathogenesis of granuloma annulare are unknown, but after reviewing the previous
      case reports we hypothesize that circulating human immunodeficiency virus
      particles may be a precipitating factor in granuloma annulare and that the CD4+
      and CD8+ cell dysfunction may be responsible for the atypically short course of
      the disease.

PMID- 7634847
TI  - Disseminated histoplasmosis in a patient with acquired immunodeficiency syndrome.
AB  - No matter how typical a cutaneous eruption may be in a patient with the acquired
      immunodeficiency syndrome, early histologic evaluation is necessary if a delay in
      diagnosis and treatment is to be avoided. We report the case of a 33-year-old man
      with acquired immunodeficiency syndrome who was clinically misdiagnosed as having
      a drug-induced eruption. Three weeks later he died with disseminated
      histoplasmosis.

PMID- 7634845
TI  - Lupus-like eruption and human immunodeficiency virus infection.
AB  - Aberrant production of antibodies has been reported in some patients infected
      with human immunodeficiency virus. However, manifestations of autoimmune disease
      are rare. A case of a human immunodeficiency virus seropositive patient with a
      high titer of antinuclear antibodies and clinical manifestations of psoriasiform
      subacute cutaneous lupus erythematosus is described.

PMID- 7634848
TI  - Pseudotumor cerebri after treatment with tetracycline and isotretinoin for acne.
AB  - Tetracyclines and isotretinoin are widely used treatments for patients with acne.
      Although generally safe, the use of these agents has been associated with
      pseudotumor cerebri and combination therapy with these agents may increase the
      risk for pseudotumor cerebri. A 14-year-old boy presented with headaches and
      bilateral visual loss secondary to papilledema. He had been treated with
      tetracycline and isotretinoin for acne for three weeks prior to presentation and
      was subsequently diagnosed as having pseudotumor cerebri. He required long-term
      medical therapy and eventually underwent bilateral optic nerve sheath
      decompression. The literature regarding pseudotumor cerebri in association with
      tetracyclines and isotretinoin treatment for acne is reviewed. Dermatologists
      should be aware of the risk of pseudotumor cerebri in patients receiving
      tetracycline or isotretinoin treatment for acne and should be particularly
      cautious about using both agents simultaneously.

PMID- 7634849
TI  - Papular mucinosis associated with acquired immunodeficiency syndrome.
AB  - Papular mucinosis, also known as lichen myxedematosus, is a rare, idiopathic
      disorder in which focal deposits of mucin accumulate in the dermis. It has been
      previously reported in two patients with human immunodeficiency virus infection;
      we describe a third such case and note the presence of a granuloma adjacent to
      the mucin deposit. We also comment on other clinical manifestations of cutaneous
      mucin deposition and granuloma formation in human immunodeficiency virus
      infection.

PMID- 7634850
TI  - "Chignon alopecia": a distinctive type of nonmarginal traction alopecia.
AB  - Localized occipital alopecia may result from traction of the hair necessary to
      form and maintain a bun (chignon) in the occipital region. Marginal alopecia in
      the patient whose hair is drawn firmly back is more familiar, although traction
      may lead to loss of hair at any site of the scalp depending on the hairdressing
      techniques used. Three women were seen with localized alopecia of the occipital
      scalp associated with the wearing of a chignon. They had previously been
      uniformly misdiagnosed as having alopecia areata. "Chignon alopecia" should be
      ruled out when the diagnosis of persistent alopecia areata at the level of the
      lambda is considered. A distinctive histopathologic finding is perifollicular
      fibrosis extending into the subcutaneous fat. Traumatic alopecia is classified
      with respect to the type of trauma, localization, and pattern within the hairy
      scalp.

PMID- 7634851
TI  - Ketoconazole 2 percent cream in the treatment of tinea pedis, tinea cruris, and
      tinea corporis.
AB  - Thirty-five dermatologists enrolled 256 patients to assess the safety and
      efficacy of ketoconazole 2 percent cream, applied once daily, in the treatment of
      tinea pedis, tinea cruris, and tinea corporis. Of these, 232 were eligible for
      efficacy evaluation based on mycologic evidence. Symptoms were assessed after
      four and eight weeks of treatment; relapse was assessed four weeks after the end
      of treatment. Total symptom scores decreased significantly during the treatment
      period. A marked or excellent response to treatment was observed in 82 percent of
      the cases. At the end of treatment 113 patients had all of their symptoms scored
      as absent or mild. Of these, three patients relapsed (2.7 percent) and had at
      least one symptom scored as moderate or severe at the follow-up visit. Only 7.2
      percent (six of eighty-three) of the patients with negative findings on potassium
      hydroxide examination at the end of treatment showed positive findings at the
      follow-up visit. Three patients reported local irritant reactions to
      ketoconazole, two of whom discontinued treatment.

PMID- 7634852
TI  - Idiopathic pulmonary fibrosis. Progress and challenge.

PMID- 7634853
TI  - Lung cancer resection. Who's inoperable?

PMID- 7634854
TI  - A new classification of parapneumonic effusions and empyema.

PMID- 7634855
TI  - The increase in asthma prevalence.

PMID- 7634856
TI  - The International Cooperative Pulmonary Embolism Registry.

PMID- 7634857
TI  - Changes in pulmonary function test results after 1 year of therapy as predictors
      of survival in patients with idiopathic pulmonary fibrosis.
AB  - The study group consisted of 58 patients with idiopathic pulmonary fibrosis (IPF)
      recognized between 1970 and 1991 who were treated for their pulmonary disease,
      survived for at least 1 year from the time of initiation of treatment, and had
      forced vital capacity (FVC) measurements at the time of diagnosis and 9 to 15
      months later. Forty-four of the patients also had a single-breath diffusing
      capacity (Dsb) measured initially and after 9 to 15 months of treatment and 33
      patients had an arterial blood gas, breathing room air at the time of diagnosis
      and 9 to 15 months into therapy. Patients' conditions were classified as
      improved, unchanged, or worse after the year of treatment based on each of the
      three pulmonary function tests. A > or = 10% increase in FVC, > or = 20% increase
      in Dsb, and > or = 5 mm Hg decrease in alveolar-arterial difference in oxygen
      partial pressure [P(A-a)O2] defined improved function. A > or = 10% decrease in
      FVC, > or = 20% decrease in Dsb, and > or = 5 mm Hg increase in P(A-a)O2 defined
      worse function. Patients with < 10% change in FVC, < 20% change in Dsb, and < 5
      mm Hg change in P(A-a)O2 were regarded as having unchanged conditions. Kaplan
      Meier survival plots and the Cox proportional hazard regression model were used
      to analyze survival time in relation to change in pulmonary function after 1 year
      of therapy. Patients with an improved or unchanged FVC at 1 year had no
      difference in survival (p = 0.75), but both showed enhanced survival compared
      with patients with a > or = 10% reduction in FVC with 1 year of treatment (p <
      0.001). Patients with an improved or unchanged Dsb at 1 year also had no
      difference in survival (p = 0.21) but again, both showed enhanced survival
      compared with patients with > or = 20% decrease in Dsb with 1 year of treatment
      (p < 0.001). Changes in gas exchange after 1 year of treatment did not correlate
      with survival in the three groups. There was a trend for longer survival in
      improved patients compared with those with worsening gas exchange, but the p
      value was not significant at 0.17. We conclude that changes in the FVC and Dsb
      after 1 year of treatment are strongly predictive of duration of survival in
      patients with IPF.

PMID- 7634858
TI  - KL-6: a serum marker for interstitial pneumonia.
AB  - KL-6 is a mucinous high-molecular weight glycoprotein, expressed on type 2
      pneumonocytes, which is reported to be elevated in the serum and bronchoalveolar
      lavage fluid of patients with interstital pneumonia. A total of 118 samples from
      112 patients were measured, including 51 samples with three classes of
      interstital lung disease and 67 samples with 6 classes of noninterstital lung
      diseases, in order to clarify whether it was a useful marker of pneumonitis
      activity. The KL-6 level was significantly higher in patients with pneumonitis
      (1,187 +/- 689 U/mL; range, 224 to 2,656 U/mL) than in patients without
      pneumonitis (309 +/- 157 U/mL; range, 123 to 855 U/mL). The KL-6 level was also
      significantly higher in patients with clinically active pneumonitis (1,497 +/-
      560) compared with inactive pneumonitis (441 +/- 276) (p < 0.001). The optimal
      criterion for separating patients with active pneumonitis from patients without
      pneumonitis was a KL-6 level of 500 to 700 U/mL according to receiver operating
      characteristic analysis. These results suggest that KL-6 is a useful marker for
      the clinical diagnosis of pneumonitis and for the evaluation of disease activity.

PMID- 7634860
TI  - Formes frustes of Churg-Strauss syndrome.
AB  - We report 4 cases of Churg-Strauss syndrome (CSS) that occurred in patients being
      treated with corticosteroids for a diagnosis of asthma. One patient had asthma,
      eosinophilia, and eosinophilic lymphadenopathy that regressed with higher doses
      of corticosteroids. The second patient had both eosinophilic tissue infiltration
      and symptoms suggestive of vasculitis, while the remaining two patients had overt
      vasculitis; in all three, vasculitis developed after tapering or discontinuation
      of corticosteroid therapy. Two patients died of their disease. We have labelled
      these cases as formes frustes CSS. Our observations suggest that some cases of
      CSS may be partially or totally suppressed by corticosteroid therapy for asthma
      for very long periods and that asthmatic subjects maintained on low-dose
      corticosteroid therapy or asthmatic subjects whose corticosteroid doses are being
      tapered should be carefully monitored for the development of CSS signs and
      symptoms.

PMID- 7634859
TI  - Pulmonary findings in patients with primary Sjogren's syndrome.
AB  - STUDY OBJECTIVE: To evaluate pulmonary findings in patients with primary
      Sjogren's syndrome (SS). DESIGN: Prospective data collection. PATIENTS: Seventeen
      consecutive nonsmoking patients with primary SS. MEASUREMENTS AND RESULTS: Mild
      radiologic parenchymal changes were seen in two patients. Pulmonary
      hyperinflation (residual volume/total lung capacity [RV/TLC] percent ratio
      measured minus [-] RV/TLC percent ratio predicted > or = 8) was observed in 9
      (53%) patients, whereas obstructive and restrictive changes were infrequently
      found in ordinary spirometry (FVC, FEV1, FEV%) (none and two cases,
      respectively). Patients with SS with hyperinflation had significantly lower
      maximal expiratory flow MEF50 (p < 0.05), MEF25 (p < 0.05), and higher total lung
      capacity (p < 0.05) and FRC (p < 0.05) values as compared with those patients
      with SS without hyperinflation. They were also more frequently dyspnoeic (six vs
      none, p < 0.02) and had higher mean serum beta 2-microglobulin levels (3.6 +/-
      1.0 mg/L vs 2.6 +/- 0.7 mg/L, p < 0.025). The levels of serum beta 2
      microglobulin correlated inversely with FVC (r = - 0.583, p < 0.01), FEV1 (r = -
      0.533, p < 0.05), diffusing capacity for carbon monoxide (r = - 0.580, p < 0.01);
      its correlation with RV/TLC percent ratio was positive and relatively significant
      (r = 0.447, 0.05 < p < 0.10). CONCLUSIONS: Pulmonary hyperinflation associated
      with diminished peripheral spirometric flow values is frequently found in
      patients with primary SS. This together with the correlation of disturbed lung
      function parameters to elevated serum beta 2-microglobulin levels suggests that
      lungs and especially small airways may be an usual target organ in primary SS.

PMID- 7634861
TI  - Thoracoscopy. A prospective study of safety and outcome.
AB  - OBJECTIVE: To assess a standard classification of adverse events and evaluate the
      safety and long-term outcome of thoracoscopy in patients with pleural disease.
      DESIGN: Prospective nonrandomized cohort study. SETTING: The Pulmonary Special
      Procedures and Nd:YAG Laser Unit of the University of California San Diego
      Medical Center, San Diego. PATIENTS: Fifty consecutive patients undergoing
      thoracoscopy for diagnosis of pleural effusion or thickening, pleurodesis, or
      empyema drainage. INTERVENTION: A list of major and minor adverse events that
      could be temporally related to thoracoscopy performed for diagnosis or treatment
      of pleural processes was established before beginning this prospective study.
      Procedures were performed using multiple point-of-entry techniques and either
      local or general anesthesia. Most procedures were performed in the operating room
      using double-lumen intubation. Patients were seen daily during hospitalization
      and at least 7, 30, and 90 days after thoracoscopy. Long-term follow-up data were
      obtained by telephone calls, clinical visits, or medical chart reviews or all of
      these, until 12 months after procedures. MEASUREMENTS: Occurrence of major and
      minor adverse events possibly related to thoracoscopy was recorded prospectively.
      Demographic and clinical data, as well as efficacy and outcome after
      thoracoscopy, were also noted. RESULTS: Fifty-two procedures were performed in 50
      patients. Median age was 60 years (range, 18 to 88 years). Thoracoscopy provided
      a diagnosis in 93% of patients with pleural disease of unclear origin.
      Pleurodesis by thoracoscopic talc insufflation was successful in 95% of cases and
      in 91% of patients with malignant pleural effusions still available for
      evaluation and follow-up examination 3 months after pleurodesis. Thoracoscopic
      drainage of empyema was successful in six of seven patients and led to referral
      for open decortication in one. There were no procedure-related deaths or
      intraoperative accidents. Open-chest surgery intervention was never required.
      Only 1 major adverse event occurred: a patient with scleroderma and trapped lung
      had recurrent pleural effusion requiring chest tube drainage 1 week after
      hospital discharge. Minor adverse events, however, were noted in ten instances
      (19%). These included fever after talc pleurodesis, asymptomatic pneumothorax
      after chest tube removal, and minor would infection in a patient with empyema.
      CONCLUSION: Using the proposed classification of major and minor adverse events,
      prospective evaluation demonstrated the safety, diagnostic utility, and long-term
      efficacy of thoracoscopy performed for diagnosis and management of pleural
      processes. Potential dangers, however, of thoracoscopy are acknowledged, and
      limitations of the procedure are addressed.

PMID- 7634862
TI  - Videothoracoscopic appearance of first and recurrent pneumothorax.
AB  - STUDY OBJECTIVE: Comparison of the videothoracoscopic appearance of first and
      recurrent pneumothorax, and assessment of a relation between endoscopic
      appearance and recurrence rate. SETTING: University hospital. PATIENTS: Eighty
      two patients, 64 men (mean age, 32.7 years) and 18 women (mean age, 31.5 years),
      were included. Patients with known underlying pulmonary disease at the time of
      hospital admission were excluded. There were 61 patients (74%) with first
      pneumothorax, and 21 patients (26%) with recurrent pneumothorax. INTERVENTIONS:
      All patients underwent videothoracoscopy under general anesthesia, with double
      lumen intubation. RESULTS: Blebs or bullae were found in 47 patients (77%) with
      first pneumothorax, and in 14 patients (67%) with recurrent pneumothorax. Bullae
      > 2 cm were found in 34 patients (56%) with first pneumothorax and 10 patients
      (48%) with recurrent pneumothorax. Patients with blebs or bullae were
      significantly older than patients with normal videothoracoscopic appearance (mean
      age, 36.5 +/- 15.7 years vs 25.3 +/- 5.8 years, p < 0.05). Adhesions were
      significantly more frequently found in patients with blebs or bullae compared
      with patients with normal thoracoscopic appearance of the lung (p < 0.05).
      Seventeen of 21 patients (81%) with normal thoracoscopic appearance were smokers.
      Of nonsmoking patients (n = 22), 82% had blebs and bullae. CONCLUSIONS: No
      significant differences in videothoracoscopic appearance were found between first
      and recurrent pneumothorax. These results suggest that recurrence after the first
      event of spontaneous pneumothorax cannot be predicted by thoracoscopic findings.
      Smoking and blebs or bullae are independent risk factors for development of
      spontaneous pneumothorax.

PMID- 7634863
TI  - Spontaneous pneumothorax. Comparison of thoracic drainage vs immediate or delayed
      needle aspiration.
AB  - In the first part of this study, 61 patients admitted for the first episode or
      the first recurrence of a spontaneous pneumothorax (SP) were randomly treated
      with thoracic drainage (TD; 28 patients) or with simple needle aspiration (NA; 33
      patients). Success rate of therapy was significantly higher with TD than with NA
      (93%, CI 84 to 100 vs 67%, CI 51 to 83; p = 0.01). Hospital stay was similar
      between the two groups (7 +/- 4.6 vs 7 +/- 5.6 days), mainly because NA was
      delayed by 72 h in 26 patients. Recurrence rates at 3 months were 29% (CI 11 to
      47%) after TD, and 14% (CI 0 to 29%) after NA (p > 0.20, NS). In the second part
      of the study, an additional population of 35 patients was treated by immediate
      NA, with a success rate of 68.5% (CI 53.5 to 83.5%), and a recurrence rate at 3
      months of 30% (CI 10 to 50%). Taken together, our results indicate that NA may be
      proposed as a first-line treatment of SP, with a successful result in two thirds
      of patients and recurrence in one fifth of patients. In patients who do not heal
      with NA, a combined risk of TD failure and short-term recurrence of 50% may be an
      incentive for undelayed surgical procedures.

PMID- 7634864
TI  - Lung scanning and exercise testing for the prediction of postoperative
      performance in lung resection candidates at increased risk for complications.
AB  - OBJECTIVE: To analyze the value of preoperative lung scanning and exercise
      testing for the prediction of postoperative complications and of the short- as
      well as long-term performance in lung resection candidates at increased risk for
      complications. DESIGN: Prospective clinical trial. SETTING: Clinical pulmonary
      function laboratory in a university teaching hospital. PATIENTS: Twenty-five
      (mean age, 63 years; 17 men) of 84 consecutive lung resection candidates were
      considered at increased risk for postoperative complications due to impaired
      pulmonary function (FEV1 < 2 L or diffusion of carbon monoxide [DCO] < 50%
      predicted, or FEV1 and DCO < or = 80% predicted combined with New York Heart
      Association dyspnea index > or = 2). INTERVENTIONS: Candidates underwent
      radionuclide ventilation/perfusion scans and exercise testing to predict
      postoperative (= ppo) values for FEV1, DCO, and maximal O2 uptake (VO2max). They
      all underwent thoracotomy for neoplastic lesions; 7 had pneumonectomies, 18
      lobectomies. Six patients had postoperative complications (within 30 days), of
      whom three died. Three and 6 months postoperatively, pulmonary function tests and
      VO2max were repeated. MEASUREMENTS AND RESULTS: In the 22 survivors, the observed
      values were then compared with the predicted values. At 3 months, there were
      excellent correlations (absolute/predicted values): for FEV1 r = 0.78 and 0.81;
      for DCO, r = 0.77 and 0.74; and for VO2max, r = 0.71 and 0.83. The means of FEV1
      and VO2max did not differ from the predicted values, whereas the predicted DCO
      was lower than the observed value (mL/min/mm Hg: 15.1 vs 17.9; percent predicted:
      59.6 vs 70.9) (p < 0.05). At 6 months, correlations remained very good for FEV1
      (r = 0.81 and 0.84) and for DCO (r = 0.76 and 0.74), but had decreased for VO2max
      to 0.56 and 0.65, respectively. All means were higher than predicted (p < 0.05)
      owing to recovery in the lobectomy group. Patients with postoperative
      complications (group B) had a lower preoperative VO2max in percent predicted
      (62.8 +/- 7.5% vs 84.6 +/- 19.7%) (p < 0.01) and also a lower VO2max-ppo (10.6 +/
      3.6 vs 14.8 +/- 3.5 mL/kg/min and 44.3 +/- 13.5 vs 68.0 +/- 20.7% predicted) (p
      < 0.05) than patients without complications (group A). A VO2max-ppo < 10
      mL/kg/min was associated with a 100% mortality. Although FEV1-ppo and DCO-ppo
      were lower in group B, the difference did not reach significance. CONCLUSIONS:
      Radionuclide-based calculations of postoperative VO2max are predictive of
      operative morbidity and mortality: a VO2max-ppo of < 10 mL/kg/min may indicate
      inoperability. Further, short-term postoperative performance is accurately
      predicted by FEV1-ppo and VO2max-ppo, but long-term function is underestimated
      after lobectomy.

PMID- 7634865
TI  - Clinical and echocardiographic correlates of symptomatic tachydysrhythmias after
      noncardiac thoracic surgery.
AB  - BACKGROUND: Supraventricular tachydysrhythmias (SVTs) following thoracic surgery
      occur with significant frequency and may be associated with increased morbidity.
      Prospective data on the etiology and importance of these dysrhythmias are sparse.
      METHODS: In 100 patients undergoing pulmonary resection without history of atrial
      dysrhythmias or previous thoracic surgery, we examined the effects of predefined
      risk factors by history, pulmonary function, and echocardiography on the
      incidence of postoperative SVT. Serial echocardiograms were performed
      preoperatively, on postoperative day 1, and again between postoperative days 2 to
      6 (median = 3) to evaluate cardiovascular function and to estimate right
      ventricular systolic pressure (RVSP) by the tricuspid regurgitation jet (TRJ)
      Doppler velocity method. RESULTS: Symptomatic postoperative SVT occurred in 18
      (18%) of the 100 patients studied at a median of 3 days after surgery and was
      disabling in 12 of 18 (67%). Digoxin loading was ineffective in controlling the
      ventricular response in 16 of 17 episodes. In the patients developing SVT,
      postoperative echocardiography revealed significant elevation of TRJ Doppler
      velocity (2.7 +/- 0.6 m/s vs 2.3 +/- 0.6 m/s, p < 0.05) but not right atrial or
      ventricular enlargement or right atrial pressure increase when compared with
      patients without SVT. Independent correlates of SVT determined in a stepwise
      logistic regression included intraoperative blood loss > or = 1 L (p = 0.0001)
      and a postoperative TRJ Doppler velocity > or = 2.7 m/s (p < 0.05). Patients who
      developed SVT had a higher rate of intensive care unit admission (p < 0.004), a
      longer hospital stay (p < 0.02), and higher 30-day mortality (p < 0.02).
      CONCLUSIONS: These prospective data suggest that increased right heart pressure
      but not fluid overload or right heart enlargement predisposes to clinically
      significant SVT after pulmonary resection. SVT may be an important marker of poor
      cardiopulmonary reserve in patients who develop significant morbidity after
      thoracic surgery. Early interventions to reduce right heart pressure may decrease
      the incidence of postoperative SVT and potentially improve overall surgical
      outcomes.

PMID- 7634866
TI  - Propafenone for conversion of recent-onset atrial fibrillation. A controlled
      comparison between oral loading dose and intravenous administration.
AB  - STUDY OBJECTIVE: To compare placebo vs two different regimens of propafenone
      administration--intravenous administration or short-term oral loading--in
      converting recent-onset atrial fibrillation to sinus rhythm. DESIGN: Single-blind
      placebo-controlled study. PATIENTS: Eighty-seven patients with atrial
      fibrillation of recent onset (< or = 7 days' duration) admitted to the hospital
      without signs of organic heart disease (n = 42) or with systemic hypertension
      without signs or symptoms of heart failure (n = 45). The patients were assigned
      randomly to treatment with intravenous propafenone (29 patients), oral
      propafenone (29 patients), or placebo (29 patients). INTERVENTIONS:
      Administration of propafenone intravenously (2-mg/kg bolus followed by 0.0078
      mg/kg/min) or as short-term oral loading (600 mg orally single dose). Patients
      were submitted to Holter monitoring and conversion to sinus rhythm was evaluated
      at 1, 3, and 8 h. RESULTS: Conversion to sinus rhythm was obtained within 1 h in
      28% with intravenous propafenone, in 3% with oral propafenone, and in 3% with
      placebo. At 3 h, the efficacy of intravenous propafenone (41%) and of oral
      propafenone (55%) were statistically superior to placebo (10% of conversions) and
      at 8 h either intravenous or oral propafenone were effective in almost two thirds
      of the patients with a statistical difference vs placebo, whose efficacy was 24%.
      No major side effects were observed. CONCLUSIONS: Propafenone as an oral loading
      dose is an efficacious and fast way of treating atrial fibrillation of recent
      onset and due to its simplicity of administration and safety can be preferred to
      the intravenous route.

PMID- 7634867
TI  - Clinical significance of fibrillatory wave amplitude. A clue to left atrial
      appendage function in nonrheumatic atrial fibrillation.
AB  - Seventy-eight patients with chronic nonrheumatic atrial fibrillation were studied
      by transesophageal echocardiography with regard to the left atrial appendage
      function and its relation to the coarseness of atrial fibrillation on
      electrocardiogram. These 78 patients (52 men and 26 women; mean age, 66 +/- 10
      years; range, 40 to 94 years) were classified into two groups according to the
      presence of coarse (group 1, n = 46; those with the greatest amplitude of
      fibrillatory wave in lead V1 > or = 1 mm) or fine (group 2, n = 32; those without
      the coarse fibrillatory wave in lead V1) atrial fibrillation on a standard 12
      lead electrocardiogram within 1 month of echocardiographic studies. There were no
      significant differences in age, sex, mean duration of atrial fibrillation, left
      ventricular end-diastolic dimension, left ventricular end-systolic dimension,
      left ventricular ejection fraction, and left atrial dimension between the two
      groups. In group 1, however, the left atrial appendage ejection fraction (24.4 +/
      14.2% vs 32.6 +/- 14.8%; p < 0.05) and the peak emptying velocity (21.7 +/- 12.6
      cm/s vs 30.4 +/- 14.3 cm/s; p < 0.01) were lower than those in group 2. There
      were higher incidences of left atrial appendage spontaneous echo contrast (26/46
      vs 7/32; p < 0.005) and thrombus (8/46 vs 0/32; p < 0.05) in group 1 patients.
      The coarse atrial fibrillation revealed a sensitivity of 80.0%, a specificity of
      58.1%, a positive predictive value of 60.9%, and a negative predictive value of
      78.1% for the presence of left atrial appendage spontaneous echo contrast and/or
      thrombus formation. In conclusion, in patients with coarse nonrheumatic atrial
      fibrillation, the left atrial appendage function is usually poor and the
      incidence of spontaneous echo contrast and thrombus formation appears to be
      higher in these patients.

PMID- 7634868
TI  - Clinical factors and angiographic features associated with premature coronary
      artery disease.
AB  - BACKGROUND: Clinical, angiographic, and biochemical features may differ in young
      patients with coronary heart disease compared with older patients. METHODS: We
      compared clinical and angiographic characteristics in 100 male patients with
      clinical onset of disease at age < or = 45 years (group 1) with those of 100
      older male patients (clinical onset of disease at > or = 60 years) (group 2). All
      patients had documented coronary artery disease. The two patient groups were
      compared in terms of the pattern of angina at disease onset, angiographic
      features, and coronary risk factors. RESULTS: Seventy-six patients in group 1 and
      49 patients in group 2 presented with acute coronary syndromes (unstable angina
      or myocardial infarction) at clinical disease onset (p < 0.001). Compared with
      patients in group 2, younger patients (group 1) showed a preponderance of single
      vessel disease (54 vs 36%; p < 0.001) and complex stenosis morphologic features
      (59 vs 36%; p < 0.01). Family history of coronary artery disease (39 vs 11%; p <
      0.001) and smoking (73 vs 46%; p < 0.001) were also more prevalent in younger
      patients. Mean plasma total cholesterol level was 6.4 +/- 1.3 mmol/L in group 1
      and 6.1 +/- 1.2 mmol/L in group 2 (p = NS). Younger patients, however, had lower
      high-density lipoprotein (HDL) cholesterol (0.9 +/- 0.2 mmol/L and 1.1 +/- 0.4
      mmol/L; p < 0.01) and higher plasma triglyceride levels compared with patients of
      group 2 (2.7 +/- 1.3 mmol/L vs 2.1 +/- 1.1 mmol/L; p < 0.001). CONCLUSIONS:
      Patients with premature coronary disease referred to coronary angiography
      commonly have unheralded acute onset of symptoms, angiographically complex
      stenosis morphologic features, and less extensive coronary artery disease. In
      addition to previously identified risk factors such as family history and
      smoking, we observed that high plasma triglyceride and low HDL cholesterol levels
      are associated with premature coronary artery disease.

PMID- 7634869
TI  - Snoring and nocturnal oxygenation. Is there a relationship?
AB  - OBJECTIVE: To test the hypothesis that snoring, independently of sleep apnea, is
      a significant determinant of nocturnal oxygen saturation. DESIGN: Prospective
      study. SETTING: Sleep disorders clinic, university teaching hospital. PATIENTS:
      Six hundred twenty-five nonapneic snorers referred to the clinic. METHODS:
      Nocturnal polysomnography, which included objective and simultaneous measurement
      of snoring and oxygen saturation, was performed in all patients. Pulmonary
      function tests and smoking history were also obtained. RESULTS: Multiple stepwise
      linear regression analysis demonstrated that age, body mass index, and pulmonary
      function were the most important determinants of nocturnal oxygen saturation,
      accounting for 20 to 30% of its variability. Snoring was a significant, although
      weak (partial r2 = 0.073, p < 0.001) determinant of lowest, but not mean,
      nocturnal oxygen saturation. When mild snorers were matched one-for-one for body
      mass index to a group of severe snorers, only the lowest, not the mean, nocturnal
      oxygen saturation was significantly different between the groups. CONCLUSIONS:
      Snoring is not associated with sustained nocturnal hypoxemia, but it is weakly
      related to lowest nocturnal oxygen saturation.

PMID- 7634870
TI  - The relationship between obesity and craniofacial structure in obstructive sleep
      apnea.
AB  - STUDY OBJECTIVE: To evaluate the interaction between craniofacial structure and
      obesity in male patients with obstructive sleep apnea (OSA). DESIGN:
      Retrospective analysis of a cohort of OSA patients. The relationships between
      neck circumference (NC), body mass index, apnea severity, and craniofacial and
      upper airway soft-tissue measurements from upright lateral cephalometry were
      examined. Patients were divided into groups; small to normal NC (group A),
      intermediate NC (group B), or large NC (group C). SETTING: A university teaching
      hospital and tertiary sleep referral center. PATIENTS: A consecutive series of
      patients with OSA who underwent polysomnography and lateral cephalometry.
      MEASUREMENTS AND RESULTS: Group A patients were less obese and had more
      craniofacial abnormalities such as a smaller mandible and maxilla and a more
      retrognathic mandible. Group B patients had both upper airway soft-tissue and
      craniofacial abnormalities. Group C patients were more obese with larger tongues
      and soft palates, and an inferiorly placed hyoid. Group C patients also had fewer
      craniofacial abnormalities than group A or B patients. There was no difference in
      airway size among the three groups. CONCLUSIONS: We conclude that there is a
      spectrum of upper airway soft-tissue and craniofacial abnormalities among OSA
      patients: obese patients with increased upper airway soft-tissue structures,
      nonobese patients with abnormal craniofacial structure, and an intermediate group
      of patients with abnormalities in both craniofacial structure and upper airway
      soft-tissue structures.

PMID- 7634871
TI  - Effects of theophylline on nocturnal sleep and daytime sleepiness/alertness.
AB  - To study the short-term effects of theophylline on sleep and wakefulness, 24
      healthy men and women, aged 21 to 35 years, received each of three doses, 0, 3,
      and 6 mg/kg, of theophylline double-blind in a Latin Square design, administered
      to 12 subjects at 9 AM and to the other 12 at 11 PM. After the daytime
      administration, sleep latency was tested at 10 AM, 12 Noon, 2 PM, and 4 PM and
      divided attention and auditory vigilance performance were tested at 10:30 AM and
      2:30 PM. After the nighttime administration, a standard 8-h polysomnogram was
      collected. On a separate day all subjects received a single 6-mg/kg dose at 9 AM
      and blood samples were drawn at 8:30 and 10:30 AM, 12:30 PM, 2:30 PM, and 4:30
      PM. The serum theophylline levels for the 6-mg/kg dose peaked at 11.0
      micrograms/mL and declined to 8.1 micrograms/mL by 4:30 PM. In the daytime
      administration, daytime mean sleep latency was increased by both doses and
      performance was improved by the high dose but not the low dose. In the nighttime
      administration, nocturnal sleep onset was delayed and total wake time was
      increased by the high dose but not the low dose. The low dose increased the
      amount of light stage 1 sleep without producing wakefulness.

PMID- 7634872
TI  - Validation of a portable sleep apnea monitoring device.
AB  - OBJECTIVE: To assess the sensitivity and specificity of a portable sleep apnea
      monitoring device (PolyG; CNS Inc; Chantassen, Minn) using standard
      polysomnography (PSG) as a gold standard. SETTING: The University of Alberta
      Hospitals Sleep Disorders Laboratory. PARTICIPANTS: One hundred and four
      consecutive patients referred for assessment of sleep complaints. MEASUREMENTS:
      Patients underwent simultaneous PSG and PolyG overnight recordings. The PSG
      included recordings of EEG, Chin electromyogram, electroculogram, ECG, oronasal
      airflow, thorax and abdomen respiratory movements, bilateral tibialis anterior
      electromyogram, and ear oximetry. The PolyG monitoring included oronasal airflow
      (thermistors), chest and abdomen pneumobelts, oximetry, ECG, and body position
      sensor. The raw data were screened and analyzed separately by two technicians
      without knowledge of results of the other system. RESULTS: The coefficient of
      correlation for apnea index (AI) was 0.94. The r value for apnea-hypopnea index
      (AHI) was 0.97. Using the criteria of AI more than 5 as diagnostic for sleep
      apnea syndrome, 23 out of the 104 patients had the disease based on PSG results.
      Twenty-six patients had AI more than 5 based on PolyG results. The sensitivity
      was 82.6% and the specificity was 91.4%. The positive predictive value was 73.1%
      and the negative predictive value was 94.9%. The overall accuracy was 89.4%.
      Using the criteria of AHI more than 15 as diagnostic for sleep apnea syndrome, 28
      of the 104 patients had the disease based on the PSG results. Twenty-four
      patients had AHI more than 15 based on PolyG results. The sensitivity was 85.7%
      and the specificity was 94.7%. The positive predictive value was 85.7% and the
      negative predictive value was 94.7%. The overall accuracy was 92.3%. CONCLUSION:
      The PolyG monitoring device is useful in identifying patients without significant
      sleep apnea.

PMID- 7634873
TI  - Predictors of patient adherence to long-term home nebulizer therapy for COPD. The
      IPPB Study Group. Intermittent Positive Pressure Breathing.
AB  - STUDY OBJECTIVE: Patients with moderate to severe COPD are frequently prescribed
      expensive and complicated therapies that require adjustments in usual activities
      of daily living. However, little is known about factors that are associated with
      adherence to such treatment. The objective of this study was to identify
      characteristics of patients who were adherent to long-term home nebulizer
      therapy. DESIGN: Patients were stratified into two adherence groups based on
      average minutes of nebulizer use each day. A logistic regression model was
      developed to predict adherence based on baseline variables. A questionnaire was
      administered to patients to assess reasons for adherence to therapy. SETTING:
      Five clinical centers in the United States and Canada. PARTICIPANTS: Nine hundred
      eighty-five patients with moderate to severe COPD enrolled in the Intermittent
      Positive Pressure Breathing (IPPB) Trial. INTERVENTIONS: Long-term home IPPB and
      nebulizer therapy. MEASUREMENTS AND RESULTS: Altogether 50.6% of patients were
      adherent, and 49.4% were nonadherent. Among baseline variables, good adherence
      was predicted by white race, married status, abstinence from cigarettes and
      alcohol, serum theophylline level > or = 9 micrograms/mL, more severe dyspnea,
      and reduced FEV1 (p < 0.05). Subjects who were adherent to nebulizer therapy were
      older, better educated, had a stable lifestyle, were more likely to report that
      the therapy made them feel better, and were more likely to keep clinic
      appointments. CONCLUSIONS: Sociodemographic, physiologic, and quality of life
      variables were associated with adherence to long-term nebulizer therapy.

PMID- 7634875
TI  - Comparing MiniWright and spirometer measurements of peak expiratory flow.
AB  - The accuracy and instrument variability of the MiniWright (Clement Clarke) peak
      expiratory flow (PEF) meter was determined with 6 of the 24 American Thoracic
      Society's (ATS) standard waveforms using a mechanical pump. Both room air and air
      heated to 37 degrees C and saturated with water vapor were used. In addition,
      MiniWright-determined PEF measurements were compared with those obtained using a
      dry rolling-seal spirometer (Ohio No. 822; Ohio Medical Products; Madison, Wis)
      from 75 subjects on 2 different days. The MiniWright average coefficient of
      variation within a waveform was found to be 2.8%. Results using heated and
      humidified air (body temperature, ambient pressure, and saturated with water:
      body conditions) were 2.5% lower than those obtained using room air. Comparisons
      with mechanically simulated PEF and with spirometry-determined peak flow in 75
      human subjects showed that MiniWright meters over-estimated flows at lower flow
      rates and slightly under-estimated flows at higher flow rates. These results
      suggest that the new "mechanical PEF" MiniWright scale should be used instead of
      the "traditional" MiniWright scale.

PMID- 7634874
TI  - Impaired bronchodilator response to albuterol in healthy elderly men and women.
AB  - BACKGROUND: Lymphocytes of normal elderly subjects and young asthmatics display
      dysfunctional beta-adrenoceptors. If beta-adrenoceptor dysfunction were found in
      senescent airways, it might help explain the pathogenesis of late onset asthma.
      METHODS: The bronchodilatory effects of albuterol after methacholine-provoked
      bronchoconstriction were compared in 17 healthy young (age 20 to 36 years) and 17
      healthy elderly (age 60 to 76 years) volunteer subjects. Albuterol was inhaled
      via dosimeter (initially 7.8 micrograms, doubling every 7.5 min) with forced
      expiratory flow at 50% vital capacity (FEF50) measured prior to each dose.
      Albuterol sensitivity was expressed as the cumulative logarithm of the area under
      the FEF50 recovery curve (AUC); a greater AUC meant lower sensitivity. On another
      study day, spontaneous recovery from methacholine was assessed similarly.
      RESULTS: There was no intergroup difference in spontaneous recovery. Despite
      lower methacholine doses provoking similar (35%) FEF50 falls in elderly subjects,
      albuterol AUC was greater in elderly subjects (6,552%.min.microgram) than young
      subjects (3,922%.min microgram; p = 0.03). Multiple regression showed that AUC
      and age were related (p = 0.02). CONCLUSION: Airway beta 2-adrenoceptor
      responsiveness is diminished in old age, suggesting that airway beta-adrenoceptor
      dysfunction may be implicated in late-onset asthma.

PMID- 7634876
TI  - Does cytomegalovirus predict a poor prognosis in Pneumocystis carinii pneumonia
      treated with corticosteroids? A note for caution.
AB  - OBJECTIVE: To examine the importance of cytomegalovirus (CMV) in bronchoalveolar
      lavage (BAL) fluid of patients with HIV-associated Pneumocystis carinii pneumonia
      (PCP) treated with adjunctive corticosteroids (CS). DESIGN: Analysis of clinical
      data during a 5-year period. SETTING: Department of infectious diseases where
      clinical and paraclinical data on patients suspected of having PCP have been
      sampled prospectively. PATIENTS: 148 consecutive patients with a first episode of
      PCP in a 5-year period. MAIN OUTCOME MEASURE: Vital status 3 months after
      diagnosis of PCP. RESULTS: Patients with PCP treated with adjunctive CS who had
      CMV cultured from BAL fluid had a two times higher mortality within 3 months from
      bronchoscopy than others (p = 0.08). This difference could not be explained by
      differences in CD4 count, PO2 or PCO2 at time of bronchoscopy. CONCLUSION: With
      the accepted usage of adjunctive CS in severe PCP, the role of CMV as a pulmonary
      copathogen may have changed. Active CMV infection may be an important cause of
      failing treatment of severe PCP in those treated with adjunctive CS.

PMID- 7634877
TI  - Serum lactate dehydrogenase (LDH) in Pneumocystis carinii pneumonia,
      tuberculosis, and bacterial pneumonia.
AB  - An increase in serum lactate dehydrogenase (LDH) activity is commonly taken to
      support the presumptive diagnosis of Pneumocystis carinii pneumonia (PCP),
      although the LDH level may also be increased in other lung infections and in a
      variety of extrapulmonary disorders. To assess its diagnostic value in patients
      with fever, lung infiltrates, and a high prevalence of HIV infection, we compared
      LDH levels in 42 hospitalized patients with PCP, 71 with disseminated
      tuberculosis (TB), 40 with pulmonary TB, and 37 with bacterial pneumonia. Peak
      LDH level was higher (p < 0.05) in patients with PCP (547 +/- 157 U/L) and
      disseminated TB (569 +/- 338 U/L) than in patients with pulmonary TB (258 +/- 66
      U/L) or bacterial pneumonia (331 +/- 139 U/L). However, substantial overlap
      between groups limited its diagnostic value for individual patients. Expressing
      LDH as its ratio to simultaneous serum aminotransferases (AST or ALT) did not
      enhance its discriminatory value. Most patients in each group had abnormalities
      in other serum enzymes (AST, ALT, alkaline phosphatase, gamma
      glutamyltransferase), making an isolated elevation of LDH level uncommon (21% of
      PCP cases). Serum LDH has a high sensitivity for PCP (100% in this series) but
      must be interpreted with caution given its lack of specificity.

PMID- 7634878
TI  - The refractory period after eucapnic voluntary hyperventilation challenge and its
      effect on challenge technique.
AB  - To evaluate whether there is a refractory period (RP) after hyperventilation
      challenge, we compared the bronchoconstrictive response to repetitive eucapnic
      voluntary hyperventilation challenge with dry, room temperature air (EVH). The
      serial challenges were identical with 11 known asthmatics hyperventilating for 6
      min at a target minute ventilation of 30 times their FEV1 measured before either
      challenge. There was a significant difference between the mean postchallenge fall
      in FEV1 to the initial EVH challenge (27.4 +/- 9.8%) and the response to the
      second EVH challenge (16.1 +/- 5.9%) (p = 0.0001), indicating refractoriness. We
      then evaluated whether 6 min of uninterrupted EVH challenge gives a similar
      bronchospastic response to that which results from an equivalent (by total minute
      ventilation) interrupted challenge of 2 min of EVH repeated three times. The mean
      post-challenge fall in FEV1 in response to this interrupted challenge was 18.9 +/
      10.6%, which was significantly different from the 27.4% fall in response to 6
      consecutive minutes of EVH (p = 0.036). This study demonstrates that there is a
      refractory period after repeated EVH challenges and this refractoriness affects
      the response to interrupted, or dosed, EVH challenge.

PMID- 7634879
TI  - Peripheral chemoreceptor function in children with myelomeningocele and Arnold
      Chiari malformation type 2.
AB  - Blunted rebreathing hyperoxic hypercapnic ventilatory and arousal responses are
      frequent in older children with myelomeningocele (MMC) and Arnold-Chiari
      malformation type 2 (ACM). In contrast, isocapnic hypoxic rebreathing ventilatory
      responses are only occasionally affected. Thus, regions mediating the hypoxic
      ventilatory response appear usually preserved in children with MMC and ACM.
      Peripheral chemoreceptor function (PCR), however, has not been critically
      assessed in these children. To study this, PCR was measured in ten children and
      adolescents with MMC and ACM with normal alveolar ventilation during wakefulness,
      and in ten sex- and age-matched controls by measuring the ventilatory responses
      induced by 100% O2 breathing, five tidal breaths of 100% N2, and vital capacity
      breaths of 15% CO2 in O2. In general, tidal breathing of 100% O2 resulted in
      smaller decreases in minute ventilation (VE) responses in patients with MMC,
      although absent VE responses to hyperoxia were found in four patients. Vital
      capacity breaths of 15% CO2 elicited similar increases in VE in five patients and
      in ten controls, but no changes in VE were found in the remaining five patients
      (p < 0.02). Acute hypoxia induced by N2 tidal breathing resulted in significant
      linear regression correlations between VE and SpO2 in five patients with MMC,
      while absent responses were measured in those same five patients with absent
      hypercapnic responses. We conclude that PCR, when assessed by acute hypoxia,
      hyperoxia, or hypercapnia is abnormal in some children with MMC and ACM,
      particularly in those demonstrating abnormal ventilation during sleep. We
      postulate that the large interindividual variability of PCR is dependent on the
      severity of brainstem involvement of PCR afferents or central respiratory
      integration sites.

PMID- 7634880
TI  - CPAP reduces inspiratory work more than dyspnea during hyperinflation with
      intrinsic PEEP.
AB  - Hyperinflation with intrinsic positive end-expiratory pressure (PEEPi) loads the
      respiratory muscles and causes dyspnea in obstructive lung disease. Continuous
      positive airway pressure (CPAP) has shown some efficacy in reducing inspiratory
      work and dyspnea. However, in obstructive lung disease, inspiratory work and
      dyspnea may be increased by additional factors that may not be affected by CPAP.
      Therefore, to study the effects of hyperinflation with intrinsic PEEP and CPAP in
      isolation, we used a mechanical analog of airway closure to increase end
      expiratory lung volume in normal subjects. In five subjects in whom inspiratory
      work was measured, increasing end-expiratory lung volume by 1 and 2 L increased
      inspiratory work per breath from 0.42 +/- 0.04 J to 1.17 +/- 0.15 J (p < 0.05
      compared with baseline) and 1.58 +/- 0.22 J (p < 0.05 compared with baseline and
      to the lesser level of hyperinflation). Although CPAP reduced work per breath and
      per minute to levels not significantly different from baseline, it had little
      effect on dyspnea. In ten subjects hyperinflated to 2.4 +/- 0.12 L above FRC,
      breathing could be sustained 19.5 +/- 4.5 min before quitting the load. This was
      increased to 26.7 +/- 5.2 min by 10 cm H2O CPAP (p = 0.052). Inspiratory dyspnea
      was modestly reduced by CPAP during these endurance trials. We conclude that CPAP
      can substantially ameliorate the respiratory work load induced by hyperinflation
      with intrinsic PEEP. However, the effects of CPAP on dyspnea and endurance are
      more limited. This suggests that the limits to breathing at high lung volumes are
      related to factors in addition to respiratory muscle work, and that CPAP may be
      of more value in reducing the work than in relieving the distress of obstructive
      lung disease.

PMID- 7634881
TI  - PET-FDG imaging and transthoracic needle lung aspiration biopsy in evaluation of
      pulmonary lesions. A comparative risk-benefit analysis.
AB  - BACKGROUND AND OBJECTIVE: Positron emission tomography (PET) utilizing 2
      [fluorine-18]-fluoro-2-deoxy-D-glucose (FDG) has been demonstrated to be highly
      accurate in differentiating benign from malignant pulmonary nodules.
      Transthoracic fine-needle aspiration biopsy (TTNA) is generally the initial
      procedure of choice in the evaluation of peripheral lesions suspected to be
      malignant. Our objective was to determine whether PET-FDG imaging, a noninvasive
      test, was equally efficacious as TTNA in the evaluation of lung lesions suspected
      to be malignant. PATIENT SELECTION: Thirty-three patients with 35 lung lesions
      who had undergone both PET-FDG imaging and TTNA were retrospectively selected
      from an ongoing prospective study of PET-FDG imaging in the evaluation of
      solitary pulmonary nodules. MEASUREMENTS: Diagnostic efficacy was determined by
      calculating sensitivity, specificity, positive and negative predictive value, and
      overall predictive accuracy for both PET-FDG imaging and TTNA in differentiating
      benign from malignant lesions. Complication rate also was documented for the two
      tests. RESULTS: The PET imaging correctly identified all 26 malignant lesions,
      including 21 lesions diagnosed by TTNA and 7 of the 9 benign lung lesions. The
      TTNA was positive for malignancy in 21 lung lesions and missed the diagnosis of
      malignancy in 5 lesions. Diagnostic sensitivity, specificity, positive and
      negative predictive value, and overall predictive accuracy was 100, 78, 93, 100,
      and 94% for PET imaging and 81, 100, 100, 64, and 86 for TTNA, respectively.
      Pneumothorax was documented in 16 patients (46%), and 9 patients (26%) required a
      chest tube. There were no complications with PET imaging. CONCLUSION: We conclude
      that PET imaging of the lung is as efficacious as TTNA, with less risk, and
      offers an alternate noninvasive option in the evaluation and management of lung
      lesions suspected to be malignant.

PMID- 7634882
TI  - Nicotine gum, 2 and 4 mg, for nicotine dependence. A double-blind placebo
      controlled trial within a behavior modification support program.
AB  - The effectiveness of nicotine gum in combination with a behavior modification
      program was studied. The nicotine dependence of participating smokers (N = 322)
      was assessed. One hundred sixty-eight smokers were labeled as high nicotine
      dependent and 154 as moderate to low dependent. In a randomized double-blind
      procedure, the high-dependent smokers were given gum containing 4 mg of nicotine
      (87) or 2 mg of nicotine (81) and the smokers with medium or low dependence were
      given gum containing 2 mg (76) or a placebo gum (78). The smokers were also
      randomized to familiarizing themselves with the medication a week before quit day
      (112) or to regular use, that is starting gum use on the quit day (122). In the
      high-dependent group, sustained and chemically verified nonsmoking rates at 6
      weeks, 1 year, and 2 years were, respectively, 60%, 39%, and 34% in the subjects
      given the 4-mg dose compared with 41%, 16%, and 16% for those using the 2-mg
      dose. In the group with medium or low dependence, the success rates at the same
      time periods were 70%, 49%, and 39% for the subjects given the 2-mg dose and 38%,
      22%, and 17% for those given placebo gum. The differences in success rates were
      significant at least at the p < 0.02% level for all comparisons. Familiarizing
      with the gum as compared with regular use gave fewer reports of side effects, 15%
      vs 34%, p < 0.001. A trend toward better success rates at 6 weeks, although not
      statistically significant, was observed for the familiarization group, 61% vs
      52%. The study shows that high nicotine-dependent smokers need higher doses of
      nicotine replacement, in this case the 4-mg dose rather than the 2-mg dose,
      whereas 2 mg is superior to placebo among less dependent smokers. These results
      compare favorably with those reported from the more recent nicotine patch
      therapy.

PMID- 7634885
TI  - Immunophenotyping of lymphocytes in bronchoalveolar lavage fluid. A new flow
      cytometric method vs standard immunoperoxidase technique.
AB  - Characterizing lymphocyte subsets in bronchoalveolar lavage fluid (BALF) by flow
      cytometry (FC) proper gating of the lymphocyte subpopulation being analyzed is
      crucial. In order to test lymphocyte gate quality for the first time we used a
      DNA-dye to evaluate plasmamembrane integrity and thus to mark off fluorescent but
      not DNA-containing particles (eg, debris). A comparative prospective study
      between this newly developed FC technique and a standard peroxidase anti
      peroxidase (PAP) method was performed. Samples of BALF from 50 patients with
      various pulmonary diseases were examined. After determination of the total cell
      yield, a differential cell count was performed. Subsequently, the immunophenotype
      of pan T lymphocyte CD3-, T-helper lymphocyte CD4-, and T-suppressor lymphocyte
      CD8-positive lymphocyte subsets was assessed with FC as well as with the PAP
      method. Both methods showed excellent correlation (CD3: r = 0.81; CD4: r = 0.97;
      CD8: r = 0.96; p < 0.05, respectively). Comparing the mean +/- SEM, FC tends to
      overestimate CD3+ cells (90.6 +/- 1.0% vs 85.8 +/- 1.3%). For CD4 (45.0 +/- 3.4%
      vs 44.4 +/- 3.4%) and CD8 (48.1 +/- 3.5% vs 46.7 +/- 3.5%), there was good
      agreement. In a clinical setting, the reliability of both methods was equivalent,
      and FC using a DNA-dye to test lymphocyte gate quality offered a rapid and
      reliable determination of lymphocyte subsets in BAL.

PMID- 7634884
TI  - Pulmonary complications associated with illicit drug use. An update.
AB  - STUDY OBJECTIVE: In earlier years, nonopportunistic infectious pulmonary
      complications of illicit drug use were most common. We designed this study to
      update the pulmonary complications associated with illicit drug use in the 1990s.
      DESIGN: Concurrent and retrospective chart review. SETTING: Inner-city municipal
      hospital. PATIENTS: All illicit drug users with pulmonary complications seen by
      the pulmonary consult service were enrolled in the study. There were 105 hospital
      admissions of 97 patients in a 14-month study period. RESULTS: Sixty percent of
      the patients had HIV infection. The most common pulmonary complications were
      Pneumocystis carinii pneumonia (30%) followed by community-acquired pneumonia
      (12%) and tuberculosis (9%). CONCLUSIONS: The spectrum of pulmonary disease in
      illicit drug users has changed since 1988. Opportunistic HIV-related disease is
      much more common. Community-acquired pneumonia and tuberculosis remain relatively
      frequent complications. Septic pulmonary embolism is now rare.

PMID- 7634883
TI  - The relationship of the 6-min walk test to maximal oxygen consumption in
      transplant candidates with end-stage lung disease.
AB  - STUDY OBJECTIVE: To assess the relationship of distance ambulated during the 6
      min walk test (6'WT) to maximal oxygen consumption (VO2 max). DESIGN:
      Multivariate analysis of patient characteristics to VO2 max. SETTING: Pre-lung
      transplant evaluation. PATIENTS: 60 patients (22 men, 38 women; mean age, 44
      years) with end-stage lung disease (mean FEV1 and forced vital capacity of 0.97
      and 1.93, respectively). MEASUREMENTS AND RESULTS: The 6'WT was performed on a
      level hallway surface, and VO2 max was obtained during maximal cycle ergometry
      exercise testing with respiratory gas analysis. Multivariate analysis of patient
      characteristics (age, sex, weight, FEV1, FVC, diffusing capacity for carbon
      monoxide (DCO), 6'WT distance ambulated, number of rests per 6'WT, and the
      maximal heart rate, blood pressure, rate-pressure product, respiratory rate,
      oxygen saturation, rating of perceived exertion, and amount of supplemental
      oxygen used during the 6'WT) was performed on two groups of 30 patients each
      (group A or B) who were randomly assigned to either group by a process of random
      selection using a computer-generated random numbers program. Distance ambulated
      was the strongest independent predictor of VO2 max (r = 0.73; p < 0.0001) in both
      groups, and adding age, weight, and pulmonary function test results (FVC, FEV1,
      and DCO) to the regression equation increased the correlation coefficient to
      0.83. Because of the significant correlation of distance ambulated during the
      6'WT to VO2 max, the prediction equation obtained from the multivariate analysis
      of group A, VO2 max = 0.006 x distance (feet) +3.38, was used to estimate the VO2
      max of the group B patients. No significant difference was observed between the
      estimated (x +/- SD = 8.9 +/- 2.4 mL/kg/min) and observed (x +/- SD = 9.4 +/- 3.8
      mL/kg/min) VO2 max (mean difference, 0.5 mL/kg/min; SD of the difference = 2.88).
      CONCLUSIONS: The distance ambulated during a 6'WT can predict VO2 max in patients
      with end-stage lung disease. The addition of several patient characteristics can
      increase the ability to predict VO2 max and account for more of the variability.
      Such information is valuable when assessing patient response to therapeutic
      intervention if respiratory gas analysis is unavailable or impractical.

PMID- 7634886
TI  - Pleural effusions in hospitalized patients receiving long-term hemodialysis.
AB  - OBJECTIVE: To determine the incidence, causes, and clinical features of pleural
      effusions in hospitalized patients receiving long-term hemodialysis. DESIGN:
      Retrospective. PARTICIPANTS: One hundred patients receiving hemodialysis for at
      least 3 months with pleural effusion hospitalized at the Medical University of
      South Carolina hospitals. RESULTS: The incidence of pleural effusions in
      hospitalized patients receiving long-term hemodialysis was 21%. The mean (+/-
      SEM) age was 55 +/- 1.4 years and the male to female and black to white ratios
      were 3:2. Pleural effusions resulted from heart failure in 46% and nonheart
      failure causes in 54%. Uremic pleurisy (n = 16), parapneumonic effusion (n = 15),
      and atelectasis (n = 11) accounted for most of the nonheart failure causes of
      pleural effusions. Three of 15 (20%) parapneumonic effusions were empyemas. The
      presence of chest pain was not different in patients with parapneumonic effusions
      than in other patients with nonheart failure effusion (all p = NS) but was more
      frequent compared to those with heart failure (p = 0.006). Patients with
      parapneumonic effusions (p = 0.0006) and atelectasis (p = 0.003) were more likely
      to have unilateral pleural effusions than patients with heart failure.
      CONCLUSIONS: Pleural effusions are common in hospitalized patients receiving
      chronic hemodialysis. Although heart failure was the most common cause, other
      diseases were responsible for most of the effusions. The presence of a unilateral
      effusion suggests a diagnosis other than heart failure, most commonly
      parapneumonic effusion or atelectasis and deserves prompt thoracentesis as these
      effusions often cannot be reliably differentiated clinically. The reduced humoral
      and cellular immunity, in addition to delay in diagnosis because of an attenuated
      clinical response, may explain the high rate of empyemas in this study
      population.

PMID- 7634887
TI  - Financial implications of noninvasive positive pressure ventilation (NPPV).
AB  - Noninvasive positive pressure ventilation (NPPV) is effective in the treatment of
      acute and chronic respiratory failure. However, the costs and financial balance
      between costs and diagnosis-related group (DRG) reimbursement for patients with
      moderate to severe respiratory failure treated with NPPV are unknown. We examined
      the costs and DRG reimbursement for 27 patients receiving Medicare referred with
      moderately severe respiratory failure for NPPV to the ventilator rehabilitation
      unit (VRU) at Temple University Hospital. This unit is one of four Health Care
      Financing Administration chronic ventilator-dependent demonstration sites that
      evaluates patients for NPPV, instructs them in home NPPV use, emphasizes
      rehabilitation, and uses strict cost accounting methods. Nineteen patients were
      treated with NPPV in the ICU and then referred to the VRU, and 8 patients were
      directly admitted for NPPV to the VRU. Patients were (mean +/- SE) 69 +/- 9 years
      age, 14 had severe COPD, and 13 had various restrictive disorders. All were
      hypercapneic at the time of hospital admission (restrictive 60 +/- 15;
      obstructive 67 +/- 3 mm Hg, PaCO2) with impaired lung mechanics and limited
      functional status. Patients averaged 8 +/- 15 days in the ICU, or 8 +/- 4.7 days
      on the medical floor prior to VRU transfer. The VRU length of stay averaged 20 +/
      18 days, for a total length of stay of 29 +/- 21 days. After implementation of
      NPPV, all patients had an improvement in gas exchange while spontaneously
      breathing and functional status that was maintained in follow-up. At 1 and 2
      years of follow-up, 74% and 63% of patients were alive, respectively. Eleven
      patients were admitted with DRG 475 (respiratory system diagnosis with ventilator
      support); however, 16 of 27 patients were admitted across five different non-475
      DRG codes with reimbursement rates ranging from $2,673 to $4,215. After DRG and
      outlier reimbursement, a total deficit of $261,948 remained (average deficit
      $9,701 per patient). However, individual patient deficits ranged from $1,113 to
      $32,892. Eighty-two percent of patients treated with NPPV incurred substantial
      financial losses that were underreimbursed across all assigned DRGs, including
      DRG 475, the highest-weighted DRG. We conclude that patients with moderate to
      severe respiratory failure receiving NPPV demonstrate an improvement in
      functional status and gas exchange that is maintained in follow-up. In addition,
      patients treated with NPPV incur high costs that are currently underreimbursed by
      the present DRG system. Newer DRG payment scales that recognize NPPV as specific
      treatment should be implemented.

PMID- 7634888
TI  - Occlusion pressure and its ratio to maximum inspiratory pressure are useful
      predictors for successful extubation following T-piece weaning trial.
AB  - STUDY OBJECTIVE: In most weaning studies, failure group patients are reventilated
      prior to extubation, thus compromising the evaluation of the applied weaning
      indices' predictive values. This study determines the usefulness of both standard
      and recent indices in predicting successful extubation following prolonged
      mechanical ventilation. DESIGN AND METHODS: Following a successful 20-min T-piece
      trial, ten traditional weaning criteria, as well as airway occlusion pressure
      (PO.1), maximal inspiratory pressure (MIP), PO.1/MIP ratio, and shallow breathing
      (F/VT) were determined in unselected patients undergoing prolonged mechanical
      ventilation. Having satisfied 8 of 10 classic weaning criteria, 67 patients were
      extubated after an additional 40 min of successful spontaneous T-piece breathing,
      and included in the study. After extubation, the tracheal tube resistive pressure
      (RP) values were measured. RESULTS: Twelve (18%) patients failed extubation. The
      failure group's average age was significantly greater (69.43 vs 48.43 years). The
      PO.1, PO.1/MIP, and F/VT values of the success (3.62 +/- 1.35 cm H2O, 0.05 +/-
      0.04, and 50 +/- 23 b.min-1.L-1) and failure (7.38 +/- 2.67 cm H2O, 0.14 +/-
      0.04, and 69 +/- 25 b.min-1.L-1) groups were significantly different (p < 0.005).
      The diagnostic accuracies of these indices were, respectively, 88%, 98%, and 73%.
      The spirometric, gas exchange, and tracheal tube RP values of the two groups
      showed no significant differences. CONCLUSION: PO.1 and PO.1/MIP ratio provide
      the best means of predicting extubation success, and they are not influenced by
      tracheal tube resistance.

PMID- 7634889
TI  - The use of risk predictions to identify candidates for intermediate care units.
      Implications for intensive care utilization and cost.
AB  - OBJECTIVE: To develop a predictive equation that estimates the probability of
      life-supporting therapy among ICU monitor admissions and to explore its potential
      for reducing cost and improving ICU utilization. DESIGN: Prospective inception
      cohort analysis. PARTICIPANTS: Forty-two ICUs in 40 US hospitals with more than
      200 beds and a consecutive sample of 17,440 ICU admissions. INTERVENTIONS: A
      multivariate equation was developed to estimate the probability of life support
      for ICU monitoring admissions during an entire ICU stay. MEASUREMENTS:
      Demographic, physiologic, and treatment information obtained during the first 24
      h in the ICU and over the first 7 ICU days. RESULTS: The most important
      determinants of subsequent risk for life-supporting (active) treatment were
      diagnosis, the acute physiology score of APACHE III, age, operative status, and
      the patient's location and hospital length of stay before ICU admission. Among
      8,040 ICU monitoring admissions, 6,180 (76.8%) had a low (< 10%) risk for
      receiving active treatment during the ICU stay; 95.6% received no subsequent
      active treatment. Review of outcomes and the type and amount of therapy received
      suggest that most low-risk ICU monitor admissions could be safely cared for in an
      intermediate care setting. CONCLUSION: Objective predictions can accurately
      identify groups of ICU admissions who are at a low risk for receiving life
      support. This capability can be used to assess ICU resource use and develop
      strategies for providing graded critical care services at a reduced cost.

PMID- 7634890
TI  - Improvement of gas exchange, pulmonary function, and lung injury with partial
      liquid ventilation. A study model in a setting of severe respiratory failure.
AB  - STUDY OBJECTIVE: To evaluate gas exchange, pulmonary function, and lung histology
      during gas ventilation of the perfluorocarbon-filled lung compared with gas
      ventilation of the gas-filled lung in severe respiratory failure. STUDY DESIGN:
      Application of gas (GV) or partial liquid (PLV) ventilation in lung-injured
      sheep. SETTING: A research laboratory at a university medical center. SUBJECTS:
      Eleven sheep 17.1 +/- 1.8 kg in weight. INTERVENTIONS: Lung injury was induced by
      intravenous administration of 0.07 mL/kg oleic acid followed by saline pulmonary
      lavage. When alveolar-arterial oxygen pressure difference (P[A-a]O2) was 600 mm
      Hg or more and PaO2 was 50 mm Hg or less with fraction of inspired oxygen of 1.0,
      bijugular venovenous extracorporeal life support (ECLS) was instituted. For the
      first 30 min on ECLS, all animals were ventilated with gas. Over the ensuing 2.5
      h, ventilation with 15 mL/kg gas was continued without intervention in the
      control group (GV, n = 6) or with the addition of 35 mL/kg of perflubron (PLV, n
      = 5). MEASUREMENTS AND RESULTS: At 3 h after initiation of ECLS, Qps/Qt was
      significantly reduced in the PLV animals when compared with the GV animals (PLV =
      41 +/- 13%; GV = 93 +/- 4%; p < 0.005). At the same time point, pulmonary
      compliance was increased in the PLV when compared with the GV group (PLV = 0.61
      +/- 0.14 mL/cm H2O/kg; GV = 0.41 +/- 0.02 mL/cm H2O/kg; p < 0.005). The ECLS flow
      rate required to maintain the PaO2 in the 50 to 80 mm Hg range was substantially
      and significantly lower in the PLV group when compared with that of the GV group
      (PLV = 25 +/- 20 mL/kg/min; GV = 87 +/- 15 mL/kg/min; p < 0.001). Light
      microscopy performed on lung biopsy specimens demonstrated a marked reduction in
      lung injury in the liquid ventilated (LV) when compared with the GV animals.
      CONCLUSION: In a model of severe respiratory failure, PLV improves pulmonary gas
      exchange and pulmonary function and is associated with a reduction in pulmonary
      pathology.

PMID- 7634891
TI  - Using tracheal pressure to trigger the ventilator and control airway pressure
      during continuous positive airway pressure decreases work of breathing.
AB  - STUDY OBJECTIVE: We evaluated the difference in work of breathing (WOB) during
      spontaneous ventilation with continuous positive airway pressure (CPAP) among
      three methods of triggering the ventilator: conventional pressure triggering,
      tracheal pressure triggering, and flow-by triggering. METHODS: In an in vitro
      model of the respiratory system consisting of a bellows (lungs) in a plastic
      canister (chest wall), spontaneous ventilation was simulated with a piston-driven
      pump (respiratory muscles). Data were recorded during CPAP of 5 cm H2O (model
      7200ae ventilator, Puritan-Bennett, Overland Park, Kan) at peak sinusoidal
      inspiratory flow rate demands of 60 and 80 L/min and airway resistances of 5 and
      20 cm H2O/L/s, with the demand flow system triggered by conventional pressure,
      tracheal pressure, or flow. Under each condition, tidal volume, pressure-time
      product (PTP), WOB, and changes in intrapleural pressure (Ppl) and airway
      pressure were recorded in real time by means of a computerized portable
      respiratory monitor (model CP-100, Bicore, Irvine, Calif). The Ppl was measured
      from within the canister, tidal volume by positioning a flow sensor between the Y
      piece of the breathing circuit and the endotracheal tube (ETT), and airway
      pressure from a catheter attached to the flow sensor. The WOB was calculated by
      the monitor in real time. RESULTS: Changes in Ppl were greatest with conventional
      pressure triggering, less with flow-by triggering, and least with tracheal
      pressure triggering. The WOB was significantly lower (approximately 50%) with
      tracheal pressure triggering than with the other two methods. With tracheal
      pressure triggering only, an effect similar to that of pressure support
      ventilation (PSV) occurred, which accounted in part for the significant decrease
      in WOB. The PTP/breath ratio correlated strongly and was a good predictor of WOB
      (r2 = 0.95). CONCLUSIONS: Compared with conventional pressure and flow-by
      methods, triggering with tracheal pressure decreased WOB significantly. This
      method of triggering may improve patient-ventilator interaction.

PMID- 7634892
TI  - Determination of vascular impedance in the peripheral circulation by
      transcutaneous pulsed Doppler ultrasound.
AB  - Instantaneous blood flow velocity characteristics and vascular impedance spectra
      derived noninvasively by pulsed Doppler ultrasound and invasively by
      electromagnetic flow probe were compared in the canine common femoral artery to
      validate the pulsed Doppler technique for determination of vascular impedance in
      the peripheral circulation. Although Doppler ultrasonography is routinely
      performed to evaluate blood flow velocity patterns in the human peripheral
      circulation; the validity of this technique to derive peripheral vascular
      impedance has yet to be investigated. Simultaneous measurements of blood flow
      velocity were determined by both noninvasive pulsed Doppler ultrasound and
      surgically implanted electromagnetic flow probe in the common femoral artery of
      eight dogs and compared in both time and frequency domains. Vascular impedance
      spectra derived from measurements of blood flow velocity determined by Doppler
      ultrasound and electromagnetic flow probe and simultaneous measurement of
      arterial pressure by a micromanometer-tipped catheter were obtained at baseline
      and after intra-arterial injection of acetylcholine in five additional dogs.
      During the first 10 to 20% of the cardiac cycle, Doppler ultrasound blood flow
      velocity was transiently greater than the simultaneously recorded electromagnetic
      blood flow velocity. During the remainder of the cardiac cycle, the two blood
      flow velocity waveforms were nearly superimposable. The frequency spectra of the
      blood flow velocity waveforms derived from Doppler ultrasound and electromagnetic
      flow probes were similar for harmonies less than 10 Hz. Vascular impedance
      spectra derived from measurements of blood flow velocity determined by Doppler
      ultrasound and electromagnetic flow probe with simultaneous measurement of
      arterial pressure by a micromanometer-tipped catheter were similar at baseline
      and after regional administration of acetylcholine. Mean vascular resistance
      (impedance at 0 Hz), characteristic impedance, and the first minima of the
      impedance modulus derived from Doppler ultrasound and electromagnetic flow probe
      blood flow velocity measurements were closely correlated at baseline and after
      dilation with acetylcholine (r > or = 0.89, p < 0.05 for all correlations).
      Doppler ultrasonography is a convenient and accurate technique for determination
      of vascular impedance in the peripheral circulation.

PMID- 7634893
TI  - Does hypoxia or hypercarbia independently affect resuscitation from cardiac
      arrest?
AB  - STUDY OBJECTIVE: In a previous cardiopulmonary resuscitation (CPR) study in
      swine, ventilation was associated with improved rate of return of spontaneous
      circulation (ROSC) compared with nonventilated animals, which had greater hypoxia
      and hypercarbic acidosis. We used the same model to determine the independent
      effect of hypoxia and hypercarbic acidosis on ROSC after cardiac arrest. DESIGN:
      Laboratory model of cardiac arrest. SETTING: University teaching hospital
      laboratory. PARTICIPANTS: Domestic swine (23 to 61 kg). INTERVENTIONS: Twenty
      four swine were randomly assigned to three groups receiving ventilation during
      CPR with 85% O2/15% N2 (control), 95% O2/5% CO2 (hypercarbia), or 10% O2/90% N2
      (hypoxia). All animals had ventricular fibrillation for 6 min without CPR, then
      CPR with one of the ventilation gases for 10 min, then defibrillation. Animals
      without ROSC received epinephrine, 85% O2, CPR for another 3 min, and
      defibrillation. MEASUREMENTS AND RESULTS: During the tenth minute of CPR, the
      hypercarbic group had more mean (SD) arterial hypercarbia than the control group
      (PCO2, 47 +/- 6, compared with 34 +/- 6; p < 0.01), and greater mixed venous
      hypercarbia (PCO2, 72 +/- 14, compared with 59 +/- 8; p < 0.05), while mean
      arterial and mixed venous PO2 was not significantly different. The hypoxic group
      had significantly less mean arterial (43 +/- 9 compared with 228 +/- 103 mm Hg)
      and mixed venous (22 +/- 5 compared with 35 +/- 7 mm Hg) PO2 when compared with
      the control group (p < 0.01), while mean arterial and mixed venous PCO2 were not
      significantly different. Thus, the model succeeded in producing isolated
      hypercarbia without hypoxia in the hypercarbic group and isolated hypoxia without
      hypercarbia in the hypoxic group. The rate of ROSC was 6/8 (75%) for the control
      group, 1/8 (13%) for the hypercarbic group, and 1/8 (13%) for the hypoxic group
      (p < 0.02). CONCLUSIONS: Both hypoxia and hypercarbia independently had an
      adverse effect on resuscitation from cardiac arrest. In this model with a
      prolonged interval of untreated cardiac arrest, adequate ventilation was
      important for resuscitation.

PMID- 7634896
TI  - Propofol as used for sedation in the ICU.

PMID- 7634895
TI  - The effect of dietary sodium on the concentrations of vasoactive intestinal
      peptide in plasma and lung.
AB  - STUDY OBJECTIVES: In this study, we sought to determine whether changes in the
      concentration of vasoactive intestinal peptide (VIP) in the lung might explain
      the increase in bronchial reactivity associated with high sodium diets. DESIGN:
      Male Sprague-Dawley rats, eight in each group, were placed on low-sodium, normal
      sodium, or high-sodium diets and distilled drinking water ad libitum for 7 days.
      On the day of study, blood was sampled to determine plasma VIP concentration and
      the lungs were harvested and snap frozen in liquid nitrogen. VIP was measured in
      plasma and tissue extracts by radioimmunoassay. RESULTS: The VIP concentrations
      in both lung and plasma varied with dietary sodium. Plasma VIP level was
      significantly higher in the rats that had received the low-sodium diet (51.45 +/-
      7.35 pmol L-1) than in the rats that had received the high-sodium diet (29.84 +/-
      6.83; p < 0.05). In the lung, VIP level was greater in the rats that had received
      the normal-sodium diet (378.13 +/- 41.68 fmol/g) than in rats that had received
      either the low-sodium diet (137.30 +/- 26.11 fmol/g; p < 0.0005) or the high
      sodium diet (182.64 +/- 28.63 fmol/g; p < 0.005). CONCLUSIONS: The lower plasma
      and pulmonary concentrations of VIP observed in rats that had received a high
      sodium diet suggest that VIP may play a role in the increased bronchial
      reactivity reported with this diet.

PMID- 7634894
TI  - Effect of YM264 on the airway hyperresponsiveness and the late asthmatic response
      in a guinea pig model of asthma.
AB  - We investigated the effects of YM264, a specific platelet-activating factor (PAF)
      antagonist, on the airway hyperresponsiveness (AH) and the late asthmatic
      response (LAR) of guinea pigs that were sensitized by exposure to aerosolized
      ovalbumin (OA). Respiratory resistance (Rrs) was determined by the oscillation
      technique. Airway responsiveness was evaluated by administering a dose of
      histamine at which the Rrs reached 200% of the baseline value (H200). Animals
      were administered 1 or 3 mg/kg of YM264 orally 30 min before and again at 3 h
      after exposure to OA. YM264 significantly suppressed AH 24 h after and 5 days
      after the exposure. YM264 also suppressed the development of the LAR and
      accumulation of eosinophils and neutrophils in the tracheal mucosa of guinea
      pigs. These observations suggest that PAF is involved in the AH and the
      development of the LAR in asthma. PAF antagonists may play a beneficial role in
      the treatment of asthma.

PMID- 7634897
TI  - Paradoxical embolism. An underrecognized problem.
AB  - Despite reports of the clinical presentations and devastating consequences of
      paradoxical embolus (PDE) for more than a century, this diagnosis continues to be
      frequently missed. Because the prevalence of patent foramen ovale (PFO) is 27 to
      35% in the normal population and the presence of deep vein thrombosis or
      pulmonary embolus may not be clinically obvious, a high suspicion for PDE is
      needed in the event of unexplained arterial occlusion. While contrast
      echocardiography and transcranial Doppler ultrasound have facilitated clinical
      recognition of PDE, the optimum approach to diagnosis requires clarification.
      Primary therapy for patients with PDE is anticoagulation, with thrombolytics
      considered in carefully selected individuals, but there is little published
      information regarding long-term treatment and outcomes. Prevention remains
      essential whenever possible. It is not yet defined whether prophylactic treatment
      of persons with recognized predispositions to PDE (eg, PFO and pulmonary
      hypertension) is beneficial.

PMID- 7634898
TI  - A 28-year-old woman with confusion and somnolence.

PMID- 7634899
TI  - Kerley B lines in AIDS.

PMID- 7634900
TI  - Muscle weakness, fatigue, and joint pain in a 52-year-old woman.

PMID- 7634901
TI  - Why is the sky blue?

PMID- 7634902
TI  - Emergency percutaneous balloon mitral valvotomy in a patient with septic shock.
AB  - We report an 18-year-old patient with severe mitral stenosis complicated by right
      lower lobe pneumonia, sepsis, and shock. Intractable low cardiac output led to an
      emergency percutaneous balloon mitral valvotomy in a patient, resulting in
      immediately improved hemodynamic parameters. We are unaware of another report of
      percutaneous balloon mitral valvotomy performed in a patient with sepsis and
      shock. This case supports previous isolated reports of the benefit from emergency
      percutaneous balloon mitral valvotomy in critical situations where thoracotomy is
      not possible due to coexisting medical problems.

PMID- 7634903
TI  - Facilitation of percutaneous dilational tracheostomy by use of a perforated
      endotracheal tube exchanger.
AB  - Endoscopic guidance during percutaneous dilational tracheostomy reduces the risk
      of paratracheal insertion of the tracheostomy tube but may impair ventilation and
      does not eliminate the possibility of premature endotracheal extubation. Use of a
      small-caliber, hollow endotracheal tube exchanger during stomal dilation in lieu
      of a fiberoptic bronchoscope allows for better ventilation and more secure airway
      control.

PMID- 7634904
TI  - Mediastinal malignant epithelioid schwannoma.
AB  - A case of mediastinal malignant epithelioid schwannoma (MES) is reported. The
      tumor probably arose in the vagal nerve, and the trachea was involved. A few
      months after excision of the primary tumor, multiple metastases appeared in lung,
      cervical spine, and neck lymph nodes. Microscopically, the tumor showed a highly
      cellular area resembling melanoma or carcinoma. Immunolabeling was done for S-100
      protein, keratin, and melanoma-associated antigen. Examination of the entire
      lesion and in situ characteristics of the tumor involving the vagal nerve were
      helpful in making the correct diagnosis. Mediastinal MES, to our knowledge, has
      not been reported to date in the English-language medical literature.

PMID- 7634905
TI  - An unusual case of lung torsion.
AB  - We report a case of complete torsion of the right lung induced by transthoracic
      needle biopsy. While a delay in diagnosis occurred, viability of the torsed lung
      was maintained, thereby allowing for effective surgical repair.

PMID- 7634906
TI  - Reflex sympathetic dystrophy following arterial blood gas sampling in the
      intensive care setting.
AB  - A 54-year-old woman developed signs and symptoms consistent with reflex
      sympathetic dystrophy in her left upper extremity following arterial puncture.
      Diagnosis was confirmed by bone scan, and sympathetic blockade with intravenous
      regional bretylium completely relieved her severe, intractable pain.

PMID- 7634907
TI  - Intractable cough associated with the supine body position. Effective therapy
      with nasal CPAP.
AB  - We describe five patients with severe nocturnal cough and daytime somnolence in
      whom the coughing attacks are triggered by assuming the supine body position.
      Quantity and quality of the nocturnal cough were evaluated in the sleep
      laboratory with and without nasal continuous positive airway pressure (N-CPAP).
      Air flow characteristics were assessed using flow volume and airway resistance
      loops. Airway anatomy was evaluated bronchoscopically. In all five patients, the
      cough had a barking quality. Flow-volume loops showed an expiratory collapse
      phenomenon in two of the patients. Endoscopically, all five patients had signs of
      airway collapse. All patients had difficulty falling asleep because of coughing
      and were awakened by it frequently. Sleep times ranged from 2.5 to 4.5 h per
      night. With N-CPAP pressures ranging from 5 to 13 cm H2O, all five patients had
      clinically significant improvement in their symptoms. Their sleep times increased
      to a range of 5 to 7.5 h per night and the daytime somnolence markedly improved
      or resolved. All five patients requested a N-CPAP unit for home use. We conclude
      that a cough that is predominantly associated with or exacerbated by the supine
      body position may be treated effectively with N-CPAP.

PMID- 7634908
TI  - Allopurinol and enalapril. Drug induced anaphylactic coronary spasm and acute
      myocardial infarction.

PMID- 7634909
TI  - Clinical trials needed for alpha 1-antitrypsin replacement therapy.

PMID- 7634910
TI  - More cases of miliary mesothelioma.

PMID- 7634911
TI  - Thoracoscopic resection of pulmonary metastases.

PMID- 7634912
TI  - Another cause of endobronchial lesions found in HIV patients.

PMID- 7634913
TI  - Use of fiberoptic bronchoscopy in the diagnosis of pleural effusions.

PMID- 7634914
TI  - Neutrophilic endotheliitis in patients with idiopathic pulmonary fibrosis.

PMID- 7634915
TI  - We need more studies on colchicine and airway reactivity.

PMID- 7634916
TI  - Regular beta-adrenergic agonists.

PMID- 7634917
TI  - Treating acute asthma.

PMID- 7634918
TI  - What respiratory abnormalities result from neuroleptics and levodopa?

PMID- 7634920
TI  - Tracheal aspirate cultures in long-term ventilated patients who have clinical
      pneumonia.

PMID- 7634919
TI  - Meditating on exhalations.

PMID- 7634921
TI  - Epidemiology of nosocomial pneumonia. New perspectives on an old disease.

PMID- 7634922
TI  - The diagnosis of pneumonia in the critically ill.

PMID- 7634923
TI  - Treatment and prevention of nosocomial pneumonia.

PMID- 7634924
TI  - Community-acquired pneumonia. Etiology, epidemiology, and treatment.

PMID- 7634925
TI  - Epidemiology and treatment of chronic bronchitis and its exacerbations.

PMID- 7634927
TI  - Tuberculosis in the 1990s. Epidemiology and therapeutic challenge.

PMID- 7634926
TI  - Outcome predictors in bronchitis.

PMID- 7634928
TI  - Social impact of respiratory infections.

PMID- 7634929
TI  - Antibiotic resistance. Do we need new therapeutic approaches?

PMID- 7634930
TI  - New therapies for ARDS.

PMID- 7634931
TI  - [Surgical approaches in the treatment of burns].
AB  - The indication for operative treatment of third-degree burns, necrectomy and the
      possibilities for closing the defects are discussed. Special problems have to be
      considered in the operative therapy of third-degree hand injuries. In cases of
      extensive burns the donor areas are mostly limited and a biological dressing must
      be used. Different kinds of wound coverage are available for the final autologous
      skin reconstruction in these patients. Last but not least, the right
      postoperative immobilisation of both the patient and the transplanted areas is
      very important for successful skin grafting.

PMID- 7634932
TI  - [Biological and molecular biology aspects of burn therapy].
AB  - Early wound closure, permanent skin replacement and management of postburn
      deformities are still unsolved problems in the treatment of burns. However,
      recent developments in biology and molecular biology provide new possibilities
      for improved therapy. This includes the enhancement of burn wound healing by
      growth factors and growth hormone, modulation of immunogenicity of skin
      allografts by gene transfer, cytokine treatment of burn sepsis and the use of
      cell membrane stabilizers in electrical injuries.

PMID- 7634933
TI  - [Homograft transplantation in severely burned patients. Principles, indications
      and possibilities].
AB  - Homologous skin transplantation has recently gained increased importance in
      treatment concepts of severely burned patients. It is used as optimal biologic
      dressing and serves as dermal matrix in autologous-homologous intermingled
      transplantations or in cultured epithelial cells (keratinocytes). The present
      clinical indications for homologous skin and the theoretical basics are
      demonstrated.

PMID- 7634934
TI  - [Keratinocyte culture and transplantation in burns].
AB  - The culture and transplantation of keratinocytes are considered an important
      progress in the treatment of severe burns. The keratinocyte grafts take best (50
      to 90%) on remaining dermal structures after deep dermal (II b) burns. Since 1988
      we culture also donor keratinocytes. They are cryopreserved in the 'skin bank' in
      large quantities. As vital wound cover they allow for a rapid and near scarless
      reepithelialization. For deep (III) burns we use composite grafts of cultured
      auto-keratinocytes on allo-dermis with increasing success (up to 75% take rate)
      without rejection.

PMID- 7634936
TI  - [Ambulatory surgery--limits and risks from the viewpoint of the established
      physician].
AB  - Within the last years day ambulatory surgery in Germany is increasing in quantity
      and quality because of the 'Gesundheitsstrukturgesetz' (GSG). This legitimates
      the claim for procedures to ensure quality. Even regarding the existing norms for
      the quality of structure and procedure day surgery is limited. In each individual
      case the surgeon and the patient have to decide whether all the conditions for an
      ambulatory operation are fulfilled.

PMID- 7634935
TI  - [Ambulatory surgery--definition, socioeconomic and legal aspects].
AB  - One of the most important intentions of GSG 1992 is the favourization of
      traditional ambulatory surgery by legislative measures. However in general
      surgery a much higher potential for a significant reduction in cases of classical
      hospitalization and thus concomitant substantial financial savings lies in short
      stay eg. one-day/one-night procedures. At present methods of laparoscopic
      cholecystectomy, thyroid surgery and herniorrhaphy-together about 50% of common
      hospital patients-are developed enough to be practiced safely under this
      strategy. In the future further suitable techniques could evolve from minor
      access surgical concepts.

PMID- 7634937
TI  - [Ambulatory surgery in trauma surgery departments].
AB  - Establishing day care and short stay surgery in trauma departments requires a
      careful estimation of the perioperative risks. Having the therapy be successful
      for each patient admitted to day care surgery should have precedence over any
      economic limitations. In day care surgery a trauma surgeon has to make sure that
      appropriate postoperative supervision is available for each patient discharged
      from the hospital. The surgeon is responsible for qualified care on an outpatient
      basis.

PMID- 7634938
TI  - [Ambulatory pediatric surgery--limits and risks from the clinical viewpoint].
AB  - Day-care surgery in childhood has to meet the same safety criteria as inpatient
      care; thus, a knowledge of the risks and limits is mandatory. The kind of
      operation, its duration, concomitant diseases, the patient's age, previous
      vaccinations, and social conditions limit the feasibility of day-care surgery.
      Premature infants under the age of 1 year should not be treated on an outpatient
      basis because of the higher incidence of early postoperative complications. Above
      all, anesthesiological problems play an important role in day-care patients;
      fortunately, most of them are minor complications. During a 14-year period 2179
      children were treated in our department on an outpatient basis, resulting in a
      total complication rate of 1.7% and unexpected inpatient care of 1.1% of the
      patients in our series. Daycare surgery can be regarded as standard treatment for
      most of the surgical routine procedures in children.

PMID- 7634939
TI  - [Ambulatory visceral surgery--limits and risks from the clinical viewpoint].
AB  - Visceral outpatient operations are well established in Dresden. Since 1978,
      13,948 cases have been operated on in general surgery. Most patients (57.8%) had
      local anesthesia; only 9.2% needed general anesthesia. A total of 9,175 patients
      (65.8%) had visceral outpatient surgery. The conditions for these operations in
      outpatients are: the patient's compliance, the cooperation of the family, an
      operating theater with complete equipment and, last but not least, a qualified
      surgical team. The pre- and postoperative management must be perfectly organized.
      Even today there are special limitation for one-day surgery. We have not yet
      introduced laparoscopy into our outpatient program. Oncological surgery can be
      performed, provided the general standards for radical tumor surgery can be
      realized. With careful selection of patients and the right indication,
      complications are rare in outpatient surgery. In only 0.7% of all cases did wound
      infections occur postoperatively. None of the patients died.

PMID- 7634940
TI  - [Morbidity and long-term survival after bronchoplastic resection of non-small
      cell bronchial carcinoma].
AB  - During the past 12 years, among 1384 operations for NSCLC, 96 (6.9%)
      bronchoplastic resections were performed. There were 68 lobectomies, 19
      bilobectomies and 9 pneumonectomies done by means of 66 sleeve resections, 28
      wedge resections and 2 resections of the tracheal bifurcation. Atelectasis and
      anastomotic dehiscence were observed in 5 and 4%, respectively. A local complete
      resection was achieved in 81%. The 30-day mortality was 4%. The results show,
      that bronchoplastic procedures represent a safe therapeutic option in the
      operative treatment of centrally located NSCLC.

PMID- 7634941
TI  - [Prognostic parameters after surgical therapy of achalasia].
AB  - For operative treatment of achalasia transabdominal myotomy combined with a
      semifundoplication was performed in 37 patients. 35 patients could be followed up
      during an average period of 41 months. 19 patients (54%) were completely and 12
      (34%) almost symptom-free. In one case a peptic esophageal stenosis developed.
      The results of operation were especially in the group of young patients under 40
      years favourable and there was no influence on results of preoperative duration
      of symptoms or number of dilatations before surgery. Transabdominal myotomy with
      semifundoplication has shown as a procedure with low complication rates and good
      long-time results for the symptomatically therapy of achalasia.

PMID- 7634942
TI  - [Should a pyloroplasty be carried out in stomach transposition after subtotal
      esophagectomy with esophago-gastric anastomosis at the neck? A prospective
      randomized study].
AB  - The effects of pyloroplasty following subtotal oesophagectomy and gastric
      substitution with cervical oesophago-gastric anastomosis were studied in a
      prospective randomized trial. 52 patients received extramucosal pyloroplasty and
      were compared to a control group of 55 patients, in whom no drainage procedure
      was performed. 6 patients died postoperatively. One of these patients died
      following the insufficiency of pyloroplasty. The other causes of death were not
      related to the performance or non-performance of pyloroplasty. Regarding to
      patients subjective self-assessment of abdominal discomfort and radiologic
      emptying of the gastric tube no statistical significant differences between both
      groups were noted 2 weeks and 6 months postoperatively. Two patients with
      pyloroplasty, but no patient of the control group, suffered 12 months
      postoperatively from severe vomiting due to fibrotic stricture of the pylorus.
      The results of this study suggest, that usually no pyloroplasty should be
      performed following subtotal oesophagectomy and interposition of a gastric tube
      with oesophagogastric anastomosis in the neck.

PMID- 7634943
TI  - [Endoscopic and surgical therapy of hemorrhagic duodenal and stomach ulcer].
AB  - The aim of this prospective clinical study was to evaluate whether a combination
      of the endoscopic hemostasis together with fibrin sealing and consecutive
      conservative therapy could reduce the frequency of recurrent bleedings, thus the
      number of operations without adversely influencing the prognosis of the disease.
      134 patients admitted to the surgical and medical hospital of the University of
      Ulm between 1/1990 and 1/1992 with bleeding gastroduodenal ulcers took part in
      this study. All patients were treated endoscopically by hypertonic saline
      solution plus epinephrine and fibrin sealant. If initial endoscopic hemostasis
      was not achieved patients were operated within 6 h after admission. Patients with
      successful initial endoscopic hemostasis were treated conservatively and
      underwent control endoscopy after 24 and 48 h. In 23 patients the initial
      endoscopic hemostasis was not successful, they had to be operated immediately. In
      111 patients endoscopic hemostasis was achieved, 20% of these patients had acute
      bleeding ulcers (Forrest Ia, b), 66% showed stigmata of fresh bleedings (Forrest
      IIa bleeding). Primary endoscopic hemostasis was achieved in 85.6% of all
      patients treated, 14.4% of patients (n = 16) developed a recurrent bleeding
      during the observation period verified by gastroscopy. Half of these patients had
      an acute bleeding at the first gastroscopy (Forrest-Ia, Forrest-Ib bleeding).
      Recurrent bleeding became apparent between day 1 and 6 after admission to the
      hospital. Two patients refused surgical intervention, the other 14 were operated
      immediately.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7634945
TI  - [Surgical quality assurance exemplified by surgical therapy of colorectal
      carcinoma].
AB  - In the period of time between September 1, 1991 and August 31, 1993 a total of
      1927 patients at 22 East German hospitals were operated for colorectal carcinoma.
      In anticipation of quality assuring aspects these surgeries were registered and
      interpreted. An application of a constant classification (pTNM, R-classification)
      at this was essential. The resection rates of 87.3% on the colon (R0-resections
      74.4%) and of 83.1% on the rectum (R0-resection 70.8%) were established in total
      patient group. Preoperative measures and technique of surgery were also
      registered. The rate of the colonic anastomosis insufficiencies was about 3.2%,
      resp. of the rectum 8.2%. Wound suppurations occurred after surgery of the colon
      in 6.5% of the cases, resp. the rectum in 9.9%. The postoperative mortality was
      7.1% in the overall patient group. The practical realization and the efficiency
      of studies for quality assurance is pointed out.

PMID- 7634944
TI  - [Is the surgeon a prognostically relevant factor after R0-resection of colorectal
      carcinoma?].
AB  - Although the principles of resection of colorectal carcinoma have been defined
      quite exactly, some studies report considerable variations in recurrence rate and
      survival between different surgeons and clinics. We have therefore evaluated
      whether this surgeon-related influence can be found within one surgical
      department if operative procedures are strictly standardized. The data of 651
      patients who underwent R0-resection of colorectal carcinoma between 1980 and 1992
      was evaluated. Since all resections were accomplished by 5 groups of surgeons who
      strictly obeyed the same principles of resection, patients were divided in 5
      groups. These 5 groups showed similar distribution of age, sex, tumor location,
      operative procedures and UICC-tumor-stages. The locoregional recurrence rate
      ranged from 1.7%-13.3% in stage I (p > 0.05), 9.3-20.6% in stage II (p > 0.05)
      and 13.6-52.4% in stage III (p < 0.05). Metachronous distant metastases occurred
      in 3.2 to 13.3% in stage I (p > 0.05), 2.9 to 16.7% in stage II (p > 0.05) and
      21.8 to 30.2% in stage III (p > 0.05). 5-year-survival-rates of the 5 groups of
      patients varied from 74.4-84.5% in stage I (p > 0.05), 61.6-76.8% in stage II (p
      > 0.05), and 38.1 to 57.7% in stage III (p < 0.05). Although the surgeon-related
      variability of these results was surprisingly high, multivariate analysis did not
      show the surgeon as a significant prognostic factor. If the same principles of
      resection are strictly obeyed within one department of surgery, the surgeon is
      not a factor of prognostic significance.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7634946
TI  - [Pancreatic function and quality of life after resection of the head of the
      pancreas in chronic pancreatitis. A prospective, randomized comparative study
      after duodenum preserving resection of the head of the pancreas versus Whipple's
      operation].
AB  - Given an indication for surgery in patients with chronic pancreatitis, such as
      distal common bile duct obstruction, duodenal stenosis, or dilated pancreatic
      duct with stones and congestion, the surgeon must decide the type of operation to
      perform. A duodenopancreatectomy, the Whipple procedure, is widely considered to
      be the gold standard. It is highly effective in relieving pain and eliminating
      the structural abnormalities noted above. Duodenum-preserving resection of the
      head of the pancreas (DPRHP) seems to be an attractive alternative to
      pancreaticoduodenectomy (PD) in the treatment of chronic pancreatitis. In a
      clinical prospective randomized trial the efficiency of both operative methods
      was investigated. Between 7/1987 and 12/1993 43 patients were randomly assigned
      to undergo either a Whipple procedure (n = 21) or DPRHP (n = 22). Data on
      postoperative course, mortality, and postoperative morbidity were compiled. As
      concerns long-term results, postoperative hormonal status (insulin, neurotensin,
      cholecystokinin, gastrin) was checked, basal and stimulated with a standardized
      meal, using standard hormonal assay kits. All patients with PD survived, whereas
      one with DPRHP died from peritonitis. Patients with DPRHP had a significant more
      rapid convalescence (16.5 vs. 21.7 days). The range for postoperative follow-up
      is from 36 months to 5.5 years. In the DPRHP group 18 patients are in good
      condition. Two had diabetes and one developed carcinoma. In the PD group one died
      from hepatic coma, 14 are in good condition and 6 developed diabetes. All gained
      body weight with an average of 6.4 vs. 4.9 kg, DPRHP vs. PD. A difference between
      DPRHP and PD was obvious for the postoperative hormonal status. Results are
      satisfactory in both groups. For patients with DPRHP however, we see a quicker
      convalescence and a significant benefit as concerns postoperative hormonal
      status.

PMID- 7634947
TI  - [The intensive care gallbladder--a transient phenomenon or a problem requiring
      therapy?].
AB  - Acute acalculous cholecystitis (AAC) is a well-known complication in
      postoperative and severely traumatized patients. Existing data of AAC originate
      from retrospective analyses and episodic case reports. In a prospective study 45
      polytraumatized patients admitted to our intensive care unit between January 1,
      1989 and June 30, 1990 were clinically and sonographically screened for this
      condition at defined time-intervals. A clinical and sonographical follow-up was
      performed annually (1991-1993). Trauma scoring was performed according to the
      Injury Severity Score (ISS) and Polytrauma Score (PTS). AAC was defined as a
      combination of hydrops of the gallbladder, an increased mural thickness (> 3.5
      mm) and the demonstration of sludge. We were able to demonstrate this diagnostic
      triad in 8 out of 45 patients (18%). As a consequence early elective
      cholecystectomy was performed in one patient. The remaining patients were treated
      conservatively. Incidence of AAC in severely traumatized patients is probably
      higher than figures so far published suggest. The systematic search for this
      condition using serial sonographic examinations and defined sonomorphological
      criteria may select individual cases for elective cholecystectomy. Ultrasound is
      a reliable method of early detection and follow-up of this complication. Trauma
      and following intensive care therapy induce a lithogenetic factor, developing
      gallstone disease in 27% of patients within an 2-3-year interval.

PMID- 7634948
TI  - [Laparoscopic cholecystectomy as standard therapy in acute cholecystitis. A
      prospective study].
AB  - Between November 1989 and May 1994 103 laparoscopic cholecystectomies were
      performed for acute cholecystitis. Conversion rate was 4.9%. Mortality was 0.
      Postoperative morbidity was 10.7% (6.8% local complications, 3.9% systemic
      complications). None of the complications lead to a reoperation, no injuries of
      the common bile duct occurred. These results compare favorably to randomized
      studies of open cholecystectomy and to published result of laparoscopic
      cholecystectomy for acute cholecystitis. Main determining factor for technical
      difficulty of the operation was the lapse of time between onset of symptoms and
      operation. This is expressed in statistically different mean operative times in
      patients with short (1-6 days) and long (7-14; 15-21 days) clinical history of
      acute cholecystitis. We therefore conclude that early surgery, in selected cases
      even emergency surgery is indicated and that in expert hands laparoscopic
      cholecystectomy can be the treatment of choice for acute cholecystitis.

PMID- 7634950
TI  - [Intersphincteric rectum resection with colosphincter pouch].
AB  - In rectal cancer the emphasis has moved towards sphincter saving resection. Tumor
      site and penetration depth decide the operative technique in low rectal cancer.
      1) Resection at the upper confinement of the anal canal. 2) Intersphincteric
      resection at the level of the dentate line. Reconstruction is achieved by a
      colonic J-pouch. From 1991 to 1994 we operated on 35 patients with an average age
      of 58.1 years. An intersphincteric resection was performed in 11 patients whose
      tumor was situated between 0 and 2 cm upwards the dentate line. 24 cancers were
      situated between 2 and 6 cm of the dentate line and were resected at the upper
      confinement of the anal canal with a linear stapler. Tumor penetration depth was
      determined endosonographically (ES). Four patients had tumor stage ES T1, 13 ES
      T2 and 18 ES T3. A J-pouch of 7-9 cm size was sutured (11) or stapled (24) to the
      anal canal. In 10 patients who underwent intersphincteric resection the pre- and
      post-operative anal pressures were determined. We did not encounter major
      complications. In three patients a leakage at the colonal anastomosis postponed
      closure of the diverting colostomy. We had no anastomotic recurrence but one
      pelvic side recurrence. Four patients developed liver metastases; in one case
      resectable. Postoperative anal sphincter pressure was reduced in all cases but
      clinically relevant only in one. This patient has frequent major soiling, three
      patients have occasional minor leak. Two patients are incontinent of gas, 26 are
      perfect continent. One patient has bowel movements every two days, 15 one per
      day, 12 two per day and 3 three per day.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7634949
TI  - [Combined liver-islet transplantation after epigastric exenteration in carcinoma
      of Vater's ampulla].
AB  - A 44 year old female underwent an upper abdominal exenteration because of an
      adenocarcinoma of the pancreas with liver metastases (T1 N1 M1). Reconstruction
      was performed by orthotopic liver transplantation and intraportal islet
      transplantation. Due to initial non function of the first liver graft, a second
      liver transplantation was performed. Thereafter, the patient received 375,000
      islet equivalents of the primary liver donor in addition to 295,400 islet
      equivalents of another donor. Six months postoperatively, the patient is off
      insulin except irregular injections of 4-6 units of insulin to protect her from
      hyperglycemia after lunch. CT scans of the liver do not show any signs of tumor
      recurrence. Upper abdominal exenteration with consecutive islet transplantation
      offers a good method of reconstruction after radical surgery in the upper
      abdomen. The oncological aspects of the procedure have to be further
      investigated.

PMID- 7634951
TI  - [Incontinence after ileo-anal pouch anastomosis--diagnostic criteria and
      therapeutic sequelae].
AB  - After ileo-pouch-anal anastomosis (IPAA) there is an increased risk of
      incontinence due to intraoperative damage of the anal sphincter. We present a new
      concept to identify a potential incontinence prior to the closure of ileostomy by
      clinical and anal manometrical examinations. In 11 of 121 (9.1%) patients we
      diagnosed a potential incontinence. By biofeedback training we could achieve in
      this way a sufficient continence after the closure of ileostomy. After an average
      of 5.0 +/- 4.3 months of training rest pressures improved from 19.3 +/- 2.1 mmHg
      to 33.0 +/- 3.5 mmHg and squeeze pressures from 60.5 +/- 27.7 mmHg to 93.5 +/-
      17.3 mmHg. Prior to IPAA patients with potential incontinence show significantly
      reduced rest pressures of 51.0 +/- 18.4 mmHg.

PMID- 7634952
TI  - [Severe impairment of peritoneal cavity muscles in intensive care patients
      (comparative anatomic studies of respiration)].
AB  - The vital function respiration is kept up by the modifiable basal activity of the
      thin muscles of the abdominal cavity. The diaphragm is an important part of the
      respiratory muscular system. The muscular system of the 'splanchnocranium'
      exhibits a normal spontaneous activity, which is mostly open in the laryngeal
      region and mostly closed in the anorectal continence organ. In animals missing an
      abdomen, e.g. turtles, we find that the complete abdominal muscle system is
      connected to the lungs functioning as respiratory muscles. The most powerful
      lungs that exist are found in birds. Their lungs, which are situated in a stiff
      thorax are only ventilated through the air compartments, mostly by the abdominal
      muscles. By this, the role of abdominal muscles for respiratory function is
      shown. We studied intensive care patients requiring ventilatory support and found
      that the electromyogram of the external abdominal oblique muscle can be impaired
      or extinguished. In some cases the cause is a polyneuropathy, which can be
      reversible. In consequence, positioning measures, as prone positioning are
      capable of preventing progressive deterioration of ventilation/perfusion
      relationship.

PMID- 7634953
TI  - [Prevention and therapy of intra-abdominal adhesions. A survey of 1,200 clinics
      in Germany].
AB  - A survey of 1200 hospitals in Germany was undertaken to estimate the current
      standards of prevention and treatment of postoperative peritoneal adhesions. The
      751 (62.2%) evaluated questionnaires showed a representative distribution
      according to postal zones and annual laparotomies. The rate of coeliotomies for
      adhesional bowel obstruction is 2.6%. Starch-powdered gloves are used in 54.2%
      and washed before operating in 69.3%. Dry swabs and towels are used in 60.7 and
      22.5%, respectively. Most of the surgeons suture the peritoneum. Adhesions are
      divided in patients with respective symptoms but without intestinal obstruction
      by 32.6% and during laparotomies for non-adhesion-related diseases by 20.4%. Long
      intestinal tubes and plication procedures are applied by 43.9 and 33.7%,
      respectively. Medication is administered for routine prophylaxis of adhesion by
      6%, for prevention of recurrencies by 17.2%. Although it has been revealed that
      adjuvant measures for prevention of adhesions are needed, as of today, no regimen
      has proofed its efficacy and gotten accepted for clinical usage.

PMID- 7634954
TI  - [Laparoscopic hernioplasty].
AB  - The laparoscopic hernioplasty is an operative technique with a biomechanical
      background. The thin-walled inguinal triangle of the abdominal wall is reinforced
      without tension. Regarding a few details this technique may repair groin hernia
      without recurrence and nearly uncomplicated.

PMID- 7634955
TI  - [The Lichtenstein plug method for repair of recurrent inguinal hernia.
      Indications, technique and results].
AB  - The Lichtenstein plug is a cylindric polypropylene prosthesis by which small
      recurrent inguinal hernias can be occluded without a formal hernia repair. In a
      series of 245 recurrent inguinal hernia repairs from 1990 to 1994, the
      Lichtenstein plug was used for 55 hernias, 22.4% of all recurrencies. Early
      postoperative complications concerned two hematomas and one sinus formation. Re
      recurrence was 3.6% (n = 2/55) after a median follow-up of 30 months. Both
      recurrencies could again be repaired under local anesthesia. For stage I and II
      recurrencies the Lichtenstein plug is the least invasive procedure and completes
      the operative armamentarium to the advantage of patients.

PMID- 7634956
TI  - [Laparoscopic transperitoneal adrenalectomy].
AB  - The laparoscopic transperitoneal adrenalectomy combines the advantages of the
      conventional transperitoneal approach with the well known advantages of minimally
      invasive surgery. The positive personal experience in 5 patients and the results
      of the literature are reported. According to these data we are dealing with a
      safe procedure requiring an acceptable operating time, little postoperative pain
      of short duration, fast recovery and a short postoperative in-hospital stay.
      Indications are benign non-hormone- as well as hormone-producing adrenal lesions.
      Until now there are no definitive size limitations. Malignant tumors should
      continue to be operated conventionally.

PMID- 7634957
TI  - [Incisional hernias after laparoscopic interventions].
AB  - The importance of the complication incisional hernia after laparoscopic surgery
      was determined by analyzing our own cases and extensive review of the literature.
      The data recorded give its incidence as 1 in 550 cases. The most frequent event
      was intestinal incarceration with a high portion of Richter's hernias. To avoid
      postlaparoscopic hernias the important step is suturing the fascia when the
      trocar diameter exceeds 5 mm. When external suturing of the fascia is impossible,
      the laparoscopic technique using the Reverdin needle is a sufficient procedure
      for fascial closure after minimally invasive surgery.

PMID- 7634958
TI  - [Laparoscopic surgery of a thoracic stomach].
AB  - We report the case of a 54-year-old patient with up-side-down-stomach with
      recurrent gastric bleeding. Reposition of the stomach, closure of the
      diaphragmatic opening with interrupted silk sutures, fundophrenicopexy and
      corpopexy to the anterior abdominal wall was done laparoscopically. Because the
      patient presented no reflux symptoms, but hypomotility of the oesophagus, no
      fundoplication was done. To prevent recurrence of the hernia a polypropylene mesh
      was fixed over the hiatus.

PMID- 7634959
TI  - [Use of an endoscopic stapler for transanal widening of anastomotic stenosis].
AB  - Postoperative anastomotic stenosis of the colorectal region are reported in 0.5
      13%. We present one patient with a benign anastomotic stenosis after resection of
      the sigmarectum who was treated using the linear cutter Endopath ELC 35.

PMID- 7634960
TI  - [Ventral hyperostosis of the cervical spine--a rare differential diagnosis of
      dysphagia].
AB  - A case of dysphagia and hoarseness due to external compression by anterior
      hyperostosis between the third and fourth cervical vertebra is reported.
      Immediate relief of the symptoms was accomplished by surgical excision of the
      hyperostosis through an antero-lateral approach. The pathogenesis of the symptoms
      with reference to literature is discussed.

PMID- 7634961
TI  - [Tracheal rupture in long-term ventilation--a rare surgical problem].
AB  - Our patient sustained a laceration of the membranous portion of the trachea with
      massive subcutaneous emphysema and pneumothorax after long-term intubation. The
      patient was successfully operated on within two hours. The importance of prompt
      diagnosis and treatment in the event of this rare complication and the different
      causative factors are outlined. The surgical and perioperative ventilation
      problems are discussed.

PMID- 7634962
TI  - [Secondary traumatic diaphragmatic hernia with incarceration--a diagnostic
      problem].
AB  - In this paper we discuss the case of a 64-year-old patient suffering from a
      traumatic rupture of the diaphragm with delayed manifestation three years after
      the trauma. The subsequent diagnostic errors gave rise to a discussion of the
      value of the physical examination, imaging methods and invasive diagnostic
      methods, particularly laparoscopy and thoracoscopy in the acute and delayed
      diagnosis of diaphragmatic injuries.

PMID- 7634963
TI  - [Ileus of the small intestine caused by a lost gallstone! A late complication of
      laparoscopic cholecystectomy].
AB  - Lost gallstones in the peritoneal cavity following laparoscopic cholecystectomy
      might cause late complications. The case presented documents a small-bowel
      obstruction caused by a lost gallstone (phi 5 cm) 3 months after laparoscopic
      cholecystectomy. Laparotomy and small-bowel resection were performed. Another 3
      months later a second laparotomy was necessary because of adhesions.

PMID- 7634964
TI  - [Successful operation of a symptomatic aneurysm of the superior mesenteric artery
      in a child with Ehlers-Danlos syndrome].
AB  - Bleeding of an aneurysm--especially of a great vessel--represents a complication
      of Ehlers-Danlos syndrome that is often lethal. A successful operation of a
      symptomatic aneurysm of the superior mesenteric artery in a 12-year old girl with
      an Ehlers-Danlos syndrome type VI is reported. The aneurysm was resected and
      replaced by a venous graft. Four years postoperatively the artery is perfectly
      patent; a new aneurysm did not develop.

PMID- 7634965
TI  - [Models of the epigastric cavity, the liver vessels and bile ducts as an anatomic
      and surgical teaching tool].
AB  - During the "Alps-Adria Hepatobiliary School" in Ljubljana a workshop was held at
      which various liver surgery techniques were performed in practice. These
      techniques required the introduction of original methods which enabled practical
      exercise on isolated liver. Plastic casts of the upper part of the abdominal
      cavity were made, as well as the corrosion models of the hepatic vessels and bile
      ducts. Isolated livers were conserved by means of freezing. The results showed
      that the freezing and thawing did not alter the consistency of livers, which made
      them useful material for surgical practice. Corrosion casts were used for
      studying three-dimensional structure of the vessels and bile ducts before the
      surgical techniques were applied. Various possibilities of further use and
      application of models and corrosion casts are discussed. The role of working on
      the models and casts for a better performance of a surgery workshop is
      emphasized.

PMID- 7634966
TI  - [From "bone suture" to modern osteosynthesis--a chronology].
AB  - The five extremely well-known principals of osteosyntheses have been developed
      since the mid 19th century. Anaesthesia and antisepsis as absolute conditions
      blossomed into the heyday of surgery. Wire was the earliest material for
      osteosyntheses, successfully applied for the first time in 1827 by Rodgers in New
      York, systematically by Lister in Glasgow since about 1870, and later used in
      form of various 'bone sutures' and cerclages. In 1963 Weber (St. Gallen)
      developed the excentric wire tension band which for the first time provided
      technical knowledge in the treatment of fractures. In 1978 Labitzke introduced
      cables instead of the rigid cerclage wire. His lateral cable tension band which
      compresses the entire fracture area by itself, clearly improves the functional
      results. 1843 after the wire came the external fixation clamp from Wutzer (Bonn),
      1886 the plate osteosynthesis from Hansmann (Hamburg), 1909 the K-wire from
      Kirschner (Greifswald) and 1939 the intramedullary nail from Kuntscher (Kiel).
      Time has changed and modernised all principals. At the moment intramedullary
      stabilizing systems are at the centre of intensive research.

PMID- 7634967
TI  - [The prepared intracutaneous suture in soft tissue defects].

PMID- 7634968
TI  - [Diagnostic score for acute abdominal pain].

PMID- 7634969
TI  - An evaluation of strategic and threshold control measures against the Karoo
      paralysis tick, Ixodes rubicundus (Acari: Ixodidae) in South Africa.
AB  - Paralysis caused by feeding female Ixodes rubicundus ticks is a major problem in
      large areas of South Africa. As the life cycle of the tick extends over a period
      of 2 years, it was hypothesized that strategic treatment of sheep with an
      acaricide over a 2 year period, timed to kill most engorging females, should
      markedly lower the biotic potential of the tick. Two flocks of sheep grazing in
      separate paddocks known to be infested with I. rubicundus were treated either
      strategically or on a threshold basis (i.e. only when tick challenge exceeded a
      predetermined critical level in terms of paralysis) for a 2 year period. The tick
      burdens of untreated control sheep running with the two flocks were monitored
      over a 4 year period and their seasonal dynamics determined. The times at which
      peak infestations occurred were similar for both flocks of sheep, but significant
      differences in mean tick burdens between the two flocks were recorded. Tick
      numbers on sheep in the strategically treated flock did not decrease during the
      third and fourth years of the trial as was expected. Possible reasons for this
      were low stocking densities, especially during times of peak abundance of adults
      and the presence of wild hosts which maintained tick populations.

PMID- 7634970
TI  - Hyalomma truncatum (Acari; Ixodidae): evidence for the inability of adult ticks
      to discriminate between colours.
AB  - Behavioural investigations into the perception and differentiation of coloured
      objects by unfed adult Hyalomma truncatum ticks revealed that silhouettes of
      blue, green, red and yellow colour, under illumination by a sun-simulating
      waveband spectrum, are perceived by the ticks and responded to equally by a
      directed response. Two green or dark grey rectangles each with a luminance
      contrast ratio of 5:1 against the white wall of the test arena in combination
      with an overlapping, equally sized dark grey or green target were consistently
      reached by ticks in a ratio of 2:1. Since the outer targets were occupied by the
      double number of ticks compared with the central silhouette this shows that the
      response is independent of the colour of the object. Investigations into target
      perception under monochromatic radiation of different wavelength ranges which
      were evenly adjusted in their irradiances revealed that ticks responded equally
      to a black target irradiated by blue, green, yellow and red light of wavelengths
      428-472, 517-563, 549-591 and 606-654 nm, respectively. These results indicate
      the lack of true colour vision in H. truncatum.

PMID- 7634971
TI  - The spatial distribution of Borrelia burgdorferi-infected Ixodes ricinus in the
      Connemara region of County Galway, Ireland.
AB  - Studies were carried out in the Connemara area of County Galway in the west of
      Ireland in order to determine the abundance and distribution of the tick, Ixodes
      ricinus and the prevalence of its infection with Borrelia burgdorferi. The tick
      was very abundant locally, in particular when associated with cattle, sheep and
      enclosed red deer. Large numbers of ticks not only occurred on the pastures, but
      also on adjacent roadside verges. No infections with B. burgdorferi could be
      demonstrated when nymphal ticks were sampled from central areas of the pastures,
      suggesting that livestock and red deer are probably not significant reservoirs of
      the spirochaete. Small numbers of infected nymphal and adult ticks were
      associated with hedges, dry stone walls, the margins of woodland adjoining
      infested pastures and in woodland from which livestock were excluded. Woodmice
      (Apodemus sylvaticus) were most numerous in such habitats and the majority were
      infected with B. burgdorferi.

PMID- 7634972
TI  - Borrelia burgdorferi sensu lato in ticks (Acari: Ixodidae) from two different
      foci in Spain.
AB  - The prevalence of Borrelia burgdorferi sensu lato in several tick species was
      studied over a 2 year period in two ecologically different areas in Spain. One
      area was an endemic area for Lyme disease, with a number of autochthonous human
      cases and supported large populations of Ixodes ricinus on cattle and birds; the
      second area was characterized by the absence of I. ricinus together with the
      presence of foxes and their associated tick species. While I. ricinus was the
      main vector of B. burgdoreri in the endemic area (with a mean prevalence of 14%
      in adults and 51% in nymphs), adults of both Ixodes canisuga and Ixodes hexagonus
      had high rates of B. burgdorferi prevalence (30 and 28%, respectively) in the
      zone where I. ricinus was absent. Immatures of Ixodes frontalis were found to be
      carriers of the spirochete only in those zones where I. ricinus is present,
      suggesting evidence for reservoir competence in a tick-bird cycle.

PMID- 7634973
TI  - Rediversion after ileal pouch-anal anastomosis. Causes of failures and predictors
      of subsequent pouch salvage.
AB  - PURPOSE: The aim of this study was to understand better the cause and
      predictability of pouch failure requiring rediversion after ileal pouch-anal
      anastomosis and to assess the ultimate outcome of patients in a large ileal pouch
      series who required rediversion. METHODS: Data from 460 patients completing ileal
      pouch-anal anastomosis at one institution were recorded from both a prospectively
      accumulated ileal pouch registry and patient medical records. RESULTS: Of 460
      patients, 21 (4.6 percent) who underwent ileal pouch-anal anastomosis required
      rediversion. Five of these patients subsequently had successful restoration of
      pouch continuity, leaving a permanent failure rate of 16 of 460 patients (3.5
      percent). The most common reasons for rediversion were pouch fistula formation
      (12) and poor functional results (5). Preoperative factors, including age,
      previous colectomy, and indication for colectomy, did not predict eventual need
      for rediversion. Patients requiring rediversion had significantly higher rates of
      postoperative complications (95 vs. 43 percent; P < 0.001). Specifically, this
      group had a higher rate of postoperative pouch fistula (57 vs. 3.4 percent; P <
      0.001). Additionally, a final diagnosis of Crohn's disease significantly
      predicted the need for rediversion. Permanent pouch failure occurred in 36.8
      percent of patients with a final diagnosis of Crohn's disease compared with 1.4
      percent of patients with a final diagnosis of ulcerative colitis (P < 0.001). All
      five salvaged patients had fistula formation in the absence of Crohn's disease.
      CONCLUSIONS: The overall rate of permanent pouch failure is low. The majority of
      failures were related to fistula formation associated with Crohn's disease or
      poor functional results. Pouches complicated by fistulas not associated with
      Crohn's disease can be salvaged with temporary rediversion.

PMID- 7634975
TI  - Coloanal anastomosis for rectal cancer. Long-term results at the Mayo and
      Cleveland Clinics.
AB  - PURPOSE: This study was designed to determine functional outcomes and rates of
      survival and recurrence of coloanal anastomosis in rectal cancer patients.
      METHODS: Between 1981 and 1991, 117 patients underwent coloanal anastomosis.
      Fifteen percent of the patients had a J-pouch; the rest had a straight coloanal
      anastomosis. Thirty-eight percent had no diverting stoma. Median distance of the
      tumor from the anal verge was 6.7 cm. RESULTS: Local recurrence rate was 7
      percent. Five-year survival was fully 69 percent. Satisfactory fecal continence
      was achieved by 78 percent of patients; no J-pouch patient had frequent
      incontinence. Sixty-two percent of the patients had major (anastomotic leak = 18
      percent) or minor complications; complications were not mitigated by a diverting
      stoma or worsened by adjuvant therapy. CONCLUSION: Although coloanal anastomosis
      is associated with a high chance of complications, the long-term outcome, in
      terms of disease-free survival and satisfactory function, is excellent.

PMID- 7634974
TI  - Anal canal inflammation after ileal pouch-anal anastomosis. The need for
      treatment.
AB  - One technique used during restorative proctocolectomy to prevent loss of
      continence involves preservation of the anal canal. This technique retains a
      small amount of colonic mucosa and transitional mucosa that may become inflamed
      or develop dysplastic or neoplastic changes. PURPOSE: This study was designed to
      determine the presence and severity of anal canal inflammation and the need for
      treatment. METHOD: Records of 217 patients with mucosal ulcerative colitis who
      underwent restorative proctocolectomy with a stapled ileal pouch-anal anastomosis
      without anal mucosectomy from 1987 through 1990 were retrospectively reviewed.
      RESULTS: Anal canal inflammation was evident on both endoscopy and biopsy in 48
      patients (22.11 percent); 18 patients (8.29 percent) had a normal ileal pouch (9
      had symptoms; 5 required topical treatment), and 30 patients (13.82 percent) had
      associated ileal pouch inflammation (23 with symptoms requiring systemic
      treatment because of pouchitis; 10 patients had concomitant topical treatment).
      CONCLUSION: Symptomatic inflammation of the retained mucosa occurred in 32 (14.7
      percent) patients. Nine (4.1 percent) patients had inflammation of the anal canal
      alone, and 23 (10.6 percent) had pouchitis in addition. The need for treatment
      occurred in 28 (12.9 percent) of the total ((2.3 percent) patients with anal
      canal inflammation and 23 (10.6 percent) with anal canal inflammation plus
      pouchitis).

PMID- 7634976
TI  - Complete reversion and prevention of rectal adenomas in colectomized patients
      with familial adenomatous polyposis by rectal low-dose sulindac maintenance
      treatment. Advantages of a low-dose nonsteroidal anti-inflammatory drug regimen
      in reversing adenomas exceeding 33 months.
AB  - PURPOSE: This nonrandomized, controlled Phase II pilot study aims at the lowest
      effective dose of rectally applied sulindac to achieve and maintain adenoma
      reversion in colectomized patients with familial adenomatous polyposis (FAP).
      METHODS: The study group (n = 15) underwent proctoscopic and laboratory follow-up
      for polyp reversion every 6 to 12 weeks. Polyp reversion was followed by dose
      reduction in predefined steps. Proliferating cell nuclear antigen/cyclin (PCNA)
      and KI-67 proliferation indices (PI) were performed by point counting.
      Prostaglandin (PG)E2 and PGF2 alpha were quantified by time-resolved competitive
      fluorescence immunoassay. RESULTS: All patients responded to therapy within 6 to
      24 weeks. Sixty and 87 percent of patients achieved complete adenoma reversion
      after 48 weeks at 53 and 67 mg of sulindac per day per patient on average,
      respectively. Reversion was evident compared with the control group. Dose
      reduction by one-sixth to one-eighth of the usual oral dose was significant
      (Mann's trend test, P < 0.05). PCNA and KI-67 PIs of adenomatous and flat mucosa
      were significantly reduced (Wilcoxon's test, P < 0.05). Correlation of PCNA and
      KI-67 PIs indicate similar reaction of different tissue structures (Spearman's
      rank correlation test, P < 0.01). Nonsteroidal anti-inflammatory drug-induced
      redifferentiation from high-grade to low-grade dysplasia occurred in all but two
      patients. Tissue-PGE2 levels were greatly reduced. Unwanted, curable side effects
      were rare (gastritis, n = 2), and laboratory controls are within detection
      limits. CONCLUSIONS: Low-dose rectal sulindac maintenance therapy is highly
      effective in achieving complete adenoma reversion without relapse in 87 percent
      of patients after 33 months. Rectal FAP phenotype should be crucial for the
      surgical decision. Colectomy with ileorectal anastomosis and regular
      chemoprevention might proceed to be a promising alternative to pouch procedures.
      Chemoprevention with lower incidence of FAP-related tumors via dysplasia
      reversion may be possible in the future.

PMID- 7634977
TI  - Cytokine production in pouchitis is similar to that in ulcerative colitis.
AB  - PURPOSE: Controversy exists as to whether pouchitis represents a reactivation of
      the immunologic mechanisms that lead to ulcerative colitis (UC). The aims of this
      study were to determine local levels of the cytokines: interleukin-1 beta (IL-1
      beta), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor
      alpha (TNF alpha) in the mucosa of patients with "asymptomatic" ileoanal pouch (n
      = 25), pouchitis (n = 9), active UC (n = 20), normal ileum (n = 15), proctitis (n
      = 10), and normal colon (n = 15). METHODS: Lamina propria mononuclear cells were
      isolated from mucosal biopsies by enzymatic dispersion and cultured for 48 hours.
      Proinflammatory cytokine levels were measured in the supernatants by enzyme
      linked immunosorbent assay. RESULTS: IL-1 beta, IL-6, IL-8, and TNF alpha
      secretions were significantly greater in pouchitis and active UC than in the
      noninflamed ileoanal pouch and normal controls (P < 0.001). There was significant
      correlation (r = 0.63, P < 0.05) between levels of cytokines expressed in
      pouchitis and active UC. CONCLUSIONS: Increased cytokine expression occurs in
      both active UC and pouchitis and to a lesser extent in the long-standing ileoanal
      pouch.

PMID- 7634978
TI  - Autogenous vaccine: the best therapy for perianal condyloma acuminata?
AB  - PURPOSE: Treatment of perianal condyloma acuminata is frustrating because most
      treatment options are fraught with high recurrence rates and patient discomfort.
      We propose that surgical excision followed by vaccination with an autogenous
      condyloma acuminata vaccine is the most effective therapy available in primary
      and recurrent perianal condyloma acuminata. METHODS: Eighty-three patients with
      perianal condyloma acuminata were treated from 1985 to 1992. Treatment was
      divided for patients as follows: surgical excision, 20; bichloroacetic acid, 10;
      podophyllin and interferon A, 5; excision followed by autogenous condyloma
      acuminata vaccination twice weekly using 0.1 ml subcutaneously for three weeks
      increasing to 1.0 ml subcutaneously for seven weeks, 43. Syphilis was diagnosed
      in seven patients; two were human immunovirus-positive. All but three patients
      were male. Of those patients treated with the vaccination protocol, 25 had
      primary and 18 had recurrent disease. RESULTS: Recurrence rates were: excision
      alone and bichloroacetic acid, 50 percent; podophyllin and interferon A, 85
      percent; whereas only 4.6 percent recurred when treated with excision and
      vaccination. Mean follow-up was 13 (range, 6-23) months. All patients treated
      with the vaccination protocol tolerated the full course of therapy. CONCLUSION:
      We believe that excision of perianal condyloma acuminata followed by autogenous
      condyloma acuminata vaccination for approximately ten weeks is the most effective
      and definitive treatment option and, moreover, should be considered in all
      patients with perianal condyloma acuminata.

PMID- 7634979
TI  - Management and prognosis of adenocarcinoma of the appendix.
AB  - PURPOSE: Adenocarcinoma of the appendix is a rare neoplasm, and controversies
      persist regarding management. The purpose of this study was to identify
      prognostic factors and define management strategies for patients with
      adenocarcinoma of the appendix. METHODS: A retrospective case series was
      conducted at three medical school teaching hospitals over a 20-year period from
      1972 to 1992. Overall survival was determined by the actuarial life table method.
      Comparisons of prognostic factors were made using exact nonparametric log-rank
      tests. RESULTS: Thirteen patients were diagnosed during the study period. Median
      age was 62 years. There were five males and eight females. The disease was not
      suspected in any patient preoperatively. Seventy-seven percent of patients had
      metastatic disease at presentation. Second primary malignancies were found in 15
      percent of patients. Thirty-eight percent of female patients had synchronous
      ovarian lesions. Median survival was 22 months, with an estimated five-year
      survival of 43 percent (95 percent confidence interval, 22-84 percent). Patients
      with colonic histology had significantly worse survival than patients with
      mucinous histology (P = 0.0093). Patients with carcinomatosis had a significantly
      worse survival than noncarcinomatosis patients (P = 0.0078). Patients who
      underwent right hemicolectomy had a better prognosis for survival than
      appendectomy patients, but the difference was not statistically significant.
      CONCLUSIONS: Carcinoma of the appendix is very difficult to diagnose
      preoperatively, and most patients are not identified until disease is advanced.
      Good prognostic factors include mucinous histology and the absence of
      carcinomatosis. Right hemicolectomy appears to be a reasonable option, although
      its superiority to appendectomy alone has not been definitively proven. High
      frequency of ovarian metastases in women suggests a role for bilateral
      oophorectomy. In addition, a complete work-up of the patient for a synchronous
      malignancy, especially in the gastrointestinal tract, should be considered.

PMID- 7634980
TI  - Chemotherapy-induced nuclear alterations of morphologic and genomic
      characteristics in a human colon cancer grafted onto nude mice.
AB  - PURPOSE: A human Dukes B colonic adenocarcinoma was grafted onto 40 nude mice.
      The mice were divided into four groups, one control and three representing
      experimental conditions. Animals in the three experimental groups received either
      adriamycin (ADR), 5-fluorouracil (5-FU), or camptothecin (CPT) over a 25-day
      period beginning 34 days after grafting. Control animals received saline on an
      identical schedule. Animals were killed 105 days after grafting. METHODS: The
      effect of therapy was assessed by three techniques: 1) tumor size was
      periodically measured during the life of the animals, 2) modifications of APC, Ki
      ras, and p53 genes were studied by polymerase chain reaction, dot-blot analysis,
      restriction analysis, and DNA sequencing, and 3) image cytometry of Feulgen
      stained material was used to characterize 15 parameters describing morphometric,
      densitometric, and textural features of tumor nuclei. RESULTS: When compared with
      controls, tumor growth (size) was maximally suppressed by treatment with CPT (P <
      or = 0.001). Growth was inhibited significantly by treatment with 5-FU (P < or =
      0.01); no statistical difference in tumor size was observed between controls and
      animals treated with ADR. Modifications of APC, Ki-ras, and p53 genes were not
      observed; however, treatment did inhibit amplification of APC and p53 genes.
      CONCLUSIONS: The 15 morphonuclear parameters were assessed to define populations
      of cell nuclei altered by chemotherapy. Although CPT maximally suppressed growth,
      it did not alter nuclear morphology when compared with controls. Treatment with
      either 5-FU or ADR resulted in nuclear morphologic alterations defined as
      distinct populations using multivariate analysis. Nonsupervised linear
      discriminant analysis was used to quantify the relative proportions of these
      populations. Four morphonuclear parameters were identified, which discriminated
      nuclei exposed to either ADR or 5-FU from controls.

PMID- 7634981
TI  - Neonatal necrotizing enterocolitis. A 12-year review at a county hospital.
AB  - PURPOSE: A retrospective, 12-year review of neonatal necrotizing enterocolitis
      was undertaken at a county hospital, with emphasis on presentation signs and
      symptoms. METHODS: Eight-two patients with presence of intramural air were
      included in the study. The following signs and symptoms were studied: evidence of
      respiratory distress, use of umbilical catheters, white blood cell count and
      temperature at presentation, time interval from birth to diagnosis and time
      interval from diagnosis to operative intervention, presence of intramural air,
      air in biliary tree or free air, changes in abdominal girth, and presence of
      occult or gross blood in stools. Comparison was done among infants who had
      surgical or medical treatment, premature and full-term infants, and infants who
      had neonatal necrotizing enterocolitis less than or more than 20 days after
      birth. RESULTS: Eleven patients had a fatal outcome, with an overall survival of
      87 percent. Sixty-four patients were treated medically and 18 had operative
      treatment. Mortality of the surgically treated group was 44 percent. Neonates who
      had surgical intervention had a left shift of the white blood cell count more
      commonly present, and all had documented abdominal distention. There were 62
      premature and 20 full-term neonates in the group. Full-term neonates developed
      neonatal necrotizing enterocolitis earlier after birth (5.3 days compared with
      15.3 days in the premature neonate group). Full-term neonates had a better
      prognosis in our series. Presentation of symptoms more than 20 days after birth
      did not change outcome. CONCLUSION: Our results reflect the experience of a
      community-based hospital. Clinical acumen remains the cornerstone of diagnosis
      and management.

PMID- 7634982
TI  - Coronary artery disease and colorectal neoplasia.
AB  - PURPOSE: This study was designed to determine whether patients with coronary
      artery disease are at elevated risk for colorectal neoplasia. METHODS: A case
      control study was conducted among consecutive patients in three colonoscopy
      practices in New York City from 1986 to 1988. All study participants completed an
      interview questionnaire covering demographics, diet, environmental and behavioral
      exposures, family and personal medical history, and other variables. For the
      present study, 298 newly diagnosed colorectal adenoma cases and 107 incident
      cancer cases were compared with 507 colonoscoped controls without colorectal
      neoplasia or other significant findings on colonoscopy. Data on history of
      coronary artery disease (angina and/or heart attack) were obtained solely from
      the study participants' questionnaire responses. RESULTS: No association was
      observed between angina, heart attack, or either and colorectal adenomas in
      males. However, prior coronary artery disease was found to be associated with
      colorectal cancer in males more than 60 years of age and with colorectal adenomas
      in females aged 50 years or younger. CONCLUSION: Men with coronary artery disease
      may be at elevated risk for subsequent colorectal cancer. Young women with
      coronary artery disease also may be at elevated risk for colorectal neoplasia.

PMID- 7634983
TI  - Neurovascular intact muscle transposition for anal sphincter repair. Experimental
      model and experience with dynamic pacing.
AB  - PURPOSE: To study muscle behavior for anal sphincter repair, radiologic,
      manometric, and histologic techniques in a dog animal model have been used.
      Special attention was given to the problem of resting length of the transposed
      muscle. METHODS: The semitendinosus muscle of the dog could be transposed
      successfully to create a new anal sphincter based on an intact neurovascular
      pedicle. The parallel-fibered muscle was split at its distal end and encircled
      around the anal canal. Manometry was performed intraoperatively and
      postoperatively. A sufficiency high basal and squeeze pressure had to be obtained
      intraoperatively to guarantee a final continent neosphincter. This could be
      realized by a progressive stretching of the muscle until maximum squeeze is
      reached. In one animal a pacemaker was implanted, and postoperatively a fixed
      sphincter stimulation protocol was started. Muscle biopsies of the normal anal
      sphincter and the neosphincter were taken. RESULTS: 1) Muscle transposition gave
      a high degree of continence in this experimental model, with a mean resting
      pressure of +/- 40 mmHg and a mean squeezing pressure of +/- 73 mmHg. 2) Electric
      stimulation of the neosphincter in one animal influenced the resting pressure but
      not the squeeze pressure. 3) Muscle fiber type composition changed toward a slow
      fiber type composition after transposition of the fast muscle and even more after
      stimulation. CONCLUSIONS: 1) Creation of a muscle cuff around the anal sphincter
      can substitute normal anal sphincter. 2) Adequate stretch of muscle fibers is
      essential for continence. 3) Electrical pacing helps preserve resting tension and
      subsequent continence.

PMID- 7634984
TI  - Effect of 5-fluorouracil and leucovorin on the integrity of colonic anastomoses
      in the rat.
AB  - PURPOSE: This study was designed to determine the effects of 5-fluorouracil and
      leucovorin on the healing of colonic anastomoses and assess the safety of
      conducting a colonic resection and anastomosis during and shortly after a course
      of this chemotherapy in a rat model. METHODS: Fifty-six male Wistar rats,
      weighing 200 to 250 gm, were divided into four groups, each consisting of 14
      animals. Animals in Group I (control group) underwent colon resection and primary
      anastomosis. Animals in Group II received 10 mg/kg intravenous 5-fluorouracil and
      10 mg/kg leucovorin once a week for four weeks and then underwent the same
      operation. Animals in Groups III and IV received the same drug dosage for six
      weeks and were operated at different intervals: Group III at one week and Group
      IV at two weeks after completion of chemotherapy. Within each group, one-half of
      the animals were sacrificed on the third postoperative day and one-half on the
      seventh postoperative day, and anastomotic bursting pressure measurements were
      performed. RESULTS: At three and seven days, mean bursting pressure of the
      anastomoses were determined: 98 mmHg and 180.7 mmHg in Group I, 95 and 197.8 in
      Group II, 85.7 and 189.2 in Group III, and 98.6 and 179.2 in Group IV,
      respectively. There was no significant difference in bursting pressure between
      treated animals and controls by the third postoperative day or by the seventh
      day. The burst occurred at the anastomosis in all specimens tested on the third
      postoperative day and in the bowel wall adjacent to the anastomosis in all
      specimens tested on the seventh postoperative day. CONCLUSION: This study
      demonstrates that the above regimen of chemotherapy has no effect on the healing
      of colonic anastomoses and that surgery can be performed safely during and
      shortly after this regimen of chemotherapy.

PMID- 7634985
TI  - Intussusception of the sigmoid colon because of an intramuscular lipoma. Report
      of a case.

PMID- 7634986
TI  - Lengthening of the mesentery using the marginal vascular arcade of the right
      colon as the blood supply to the ileal pouch.
AB  - PURPOSE: Creation of a safe ileal pouch requires a tension-free anastomosis. The
      aim of this study was to evaluate a technical procedure that increases the length
      of the mesentery while preserving the blood supply to the ileal pouch.
      HYPOTHESIS: Preservation of the marginal vascular arcade (MVA) of the right colon
      will allow ligation of more mesenteric vessels and increase the mesenteric
      length. METHODS: Six fresh cadavers were dissected. Measurement of the apex of
      the terminal ileum was done in relation to the pubic symphysis. Measurements were
      taken after 1) complete mobilization of the terminal ileum, right colon, and
      hepatic flexure; 2) vascular ligation between colon wall and the MVA, preserving
      the latter from the right branch of the middle colic artery to the ileal branch
      of the ileocolic artery (ICA); 3) ligation of the distal third of the superior
      mesenteric artery; 4) ligation of the ICA at its origin; 5) ligation of the right
      colon artery; and 6) division of the terminal ileal mesentery. RESULTS: This
      technique enabled complete division of the terminal ileal mesentery, adding a
      mean additional 3.6 (range, 2.5 - 5.0) cm (36.5 +/- 16.5 percent) in length to
      the mesentery, compared with superior mesenteric artery, ICA, and right colic
      artery ligation. CONCLUSION: Patients who have a shorter mesentery and concern of
      excessive mesenteric tension should have colectomy performed, preserving the MVA
      from the middle colic artery to the ileal branch of the ICA. The preserved MVA
      can be a reliable alternative blood supply to the pouch if more mesenteric vessel
      ligations are necessary.

PMID- 7634987
TI  - Serum erythropoietin levels in patients with severe anemia secondary to
      inflammatory bowel disease and the use of recombinant human erythropoietin in
      patients with anemia refractory to treatment.

PMID- 7634988
TI  - The UV Scenario for Senile Cataract: Fact or Fiction? Proceedings of an expert
      workshop. Rotterdam, the Netherlands, January 31-February 1, 1994.

PMID- 7634989
TI  - Cataract and UV radiation.
AB  - The idea that UV radiation causes cataract has superficial biological
      plausibility based upon studies of UV-B on lens components, whole lenses and
      experimental animals. However, epidemiological studies on man, particularly
      geographical studies, are highly confounded by socioeconomic factors and yield
      little information. Population-based exposure-cataract studies are preferable
      since UV incidence versus UV exposure can be weighted with respect to risk and
      protective factors. However, the cataractogenic potency of UV seems to be low and
      certainly lower than the cataractogenic potency of factors such as repeated
      diarrhoea so that it is doubtful whether a clear answer to the question 'Does UV
      cause cataract' will ever be provided.

PMID- 7634991
TI  - In vivo studies on the effect of UV-radiation on the eye lens in animals.
AB  - Ultraviolet light is a non-ionizing radiation that induces photochemical
      reactions in the tissue. Its spectral A and B ranges are partially absorbed by
      the cornea and/or lens thus causing damage on the cellular, cell physiological
      and molecular level. UV-A does not seem to damage the cornea permanently and its
      effects in the lens have a very prolonged latency period. Typical reactions of
      the cornea are oedema, punctuate keratitis (photoelectric keratitis) and
      neovascularization. In the lens all reactions that could be evidenced, were
      located in the epithelium and in the outer cortical fiber cells. In vivo UV-A
      induces swelling and slight vacuolation of the anterior suture system, but apart
      from these transient effects, only very limited permanent damage could be
      demonstrated. UV-B induces the formation of an anterior subcapsular cataract,
      starting also with vacuolation of the suture system. These morphological
      characteristics can be visualized at the slitlamp microscope. Histologically,
      sutural irregularities (UV-A) and epithelial hyperplasia with capsular
      multiplication (UV-B) as well as disintegration of the anterior suture system
      could be observed. Patho-physiologically, a reduction of lens fresh weight (UV-B)
      as well as changes of the equilibrium of reduced and oxidized glutathione
      (GSH/GSSG) could be demonstrated. On the protein-biochemical level, changes in
      the ratio of water-soluble versus water-insoluble protein could be evidenced, as
      well as effects on specific crystallin fractions, namely alpha-crystallin. In
      addition, the appearance of a newly synthetized 31 kDa protein could be
      demonstrated in UV-B irradiated mice.

PMID- 7634990
TI  - A review of the evidence that ultraviolet irradiation is a risk factor in
      cataractogenesis.
AB  - There are two approaches to the question of whether solar radiation contributes
      to human cataract. The first, epidemiological studies, investigates correlations
      between man's environmental UV dose and cataract frequency. The second, animal
      models, investigates the effects of varying UV strengths and spectra on lens
      opacification in vivo or in vitro. While the latter approach typically provides
      for direct evidence, the data must still be extrapolated to human lenses. Results
      of physiological studies suggest that UV photons interact with proteins of the
      epithelial cell membranes, in particular tryptophan residues, transport ATPases
      and cytoskeletal proteins. One hypothesis is that damage to ion pumps and
      channels accumulates over the years as repair processes incompletely restore
      membrane function. Peroxidative damage is likely in view of the formation of UV
      induced lipid peroxides in the lens epithelial membranes. Loss of homeostatic
      control of ions, particularly Ca++, leads to crystallin disorder in small regions
      of the underlying fiber cells. In our diabetic cataract studies, intracellular
      Ca++ electrodes detected large shifts in intracellular Ca++ before bulk-lens
      changes were apparent. Similar occurrences likely characterize UV cataract. Our
      lab is one of few studying lens physiology and how it is altered following
      transient exposures to UV-B and UV-A, both of which pass through the cornea. Some
      changes include: loss of epithelial cell GSH; elevated Ca++; loss of membrane
      voltage; impaired transport of Na+; increased permeability to ions and water;
      inhibition of critical enzymes; and a decrease in the rate of membrane synthesis.

PMID- 7634992
TI  - UV-mediated cataractogenesis: a radical perspective.
AB  - A number of epidemiologic and experimental studies indirectly support the idea
      that solar ultraviolet radiation may be cataractogenic. However, the physical and
      cellular processes which might be involved in such cataractogenesis are by no
      means clear. Because a major consequence of the UV irradiation of oxygenated
      organic matter is the production of activated oxygen species, the involvement of
      oxidants has been suspected to be of importance. However, because the lens may
      normally exist in an hypoxic or even anoxic environment, the extent of
      availability of oxygen for such reactions is presently unknown. So also are the
      possible mechanism through which putative UV damage of the lens might eventuate
      in cataract. In addition to possible rapid and direct lethal damage to lens
      epithelium, possible cumulative damage to both lenticular DNA and proteins may
      occur. Furthermore, UV radiation has the potential to photolytically destroy
      light-sensitive nutrients and to generate damaging oxidants through interaction
      with ferruginous compounds. Given that Nature has probably provided the lens with
      substantial protective devices to ward off damaging effects of UV light, it is
      still an open question as to whether solar radiation contributes to cataract
      formation and, if so, by what mechanisms.

PMID- 7634993
TI  - UV radiation ocular exposure dosimetry.
AB  - Cataractogenesis by ultraviolet radiation (UVR) has been shown convincingly by a
      host of different laboratory studies. However, crucial epidemiological evidence
      linking chronic UVR exposure of age-related cataract appears to be lacking, since
      different environmental studies have led to apparently conflicting results. This
      paper explores a possible explanation for these conflicting results: errors in
      dosimetry. Any epidemiological study depends upon good dosimetry of the subjects'
      exposures. A careful examination of the biophysical, physiological and behavioral
      factors which determine the level of UVR exposure of the lens reveals a number of
      surprises which should explain the apparently conflicting epidemiological
      results. It is shown that geometrical and behavioral factors related to sunlight
      are so important, that by overlooking these factors, past epidemiological studies
      of UVR and cataract could readily be expected to produce conflicting results.

PMID- 7634994
TI  - UV-B and early cortical and nuclear changes in the human lens.
AB  - Experimental studies in mice and rats have shown that UV (B) irradiation leads to
      specific lens changes, viz. yellowing of the nucleus and a multilayered
      epithelium in the anterior pole with disrupted cortical fibres underneath.
      Biomicroscopic and ultrastructural studies on ageing human lenses revealed
      yellowing of the lens nucleus and locally ruptured membranes and small opacities
      in the equatorial cortex. No changes in the anterior pole were ever observed.
      This discrepancy between the human and animal lens, contraindicating UV as an
      important risk factor for human cataract, is discussed and may be due to several
      factors: (1) a difference between the high level acute and low level chronic
      irradiation; (2) species differences: nocturnal animals may be unable to cope
      with bright light exposure; (3) differences in scavenger and other defense
      mechanisms between humans and animals.

PMID- 7634995
TI  - Cataract classification.
AB  - Opacifications of the eye lens--generally defined as cataracts--develop in
      various different parts of the lens. Therefore, one has to differentiate the
      types of opacities. For epidemiological studies it is prerequisite to classify
      the cataracts according to their localization within the lens as well as to the
      size and intensity of the opacified area. Two approaches have been used in the
      past: 1) subjective methods of lens observation (based on slit lamp microscopy)
      and 2) objective methods with measurements of lens transparency or lens opacity
      respectively based on slit image documentation according to the Scheimpflug
      principle combined with the retroillumination technique. With ageing, the light
      transparency of the lens is subjected to considerable changes. Even without the
      formation of an opacity the transmission of the wavelengths in the UV-B/UV-A and
      the visible range is diminished. The single lens layers are affected by this
      phenomenon to different degrees. These changes which might also indicate an early
      stage of 'cataract formation' cannot be discerned by subjective methods. The
      densitometric image analysis of Scheimpflug slit images, however, allows the
      exact measurement of the light scatter in the single lens layers and enables the
      early recognition of disturbances in transparency which is of crucial importance
      particularly in cataract epidemiology. In view of our present knowledge the
      evaluation of risk factors which might be of importance in multifactorial
      cataract processes will hardly be possible by carrying out prevalence and/or
      incidence studies involving a single examination of the population. In this case
      follow-up studies (cohort studies) with repeated examinations are prerequisite.
      The 'objective methods' for classification alone are able to ensure the necessary
      reproducibility and the possibility to measure transparency changes in the lens
      before visible (and therefore subjectively recognizable) opacifications occurred.
      The methodical procedure with respect to an epidemiological study on the
      involvement of UV-B radiation in the processes of cataract formation in man
      requires the application of objective methods for cataract classification.

PMID- 7634996
TI  - Population based cataract epidemiological surveys utilising a photodocumentation
      system.
AB  - For the past 10 years, the authors have performed cataract epidemiological
      surveys in several places. All of them were principally population based and
      applied new types of photodocumentation systems which were developed by our
      department. The survey places in Japan were Noto, our main survey field located
      in the centre of the main island of Japan, one village in the subtropical island
      of Okinawa, a village in the northern island of Hokkaido and one village
      (Bukittinggi) in West-Sumatra, Indonesia, very close to the equator. The survey
      methods applied including an interview and ophthalmological examinations, were
      almost identical in each place and the authors believe that the quality of the
      examinations was at high level. The cataract classification and grading systems
      applied were those established by the Japanese Co-operative Cataract Epidemiology
      Study Group. At present, no significant prominent difference of cataract
      prevalence and distribution of cataract types have been found in the three Japan
      survey places. The distribution of cataract types in the Indonesian subjects
      however, was different from the Japanese subjects. The lens transparency ratio in
      the Noto survey was quite similar to that of a Dutch study. From photographic
      images of both opaque and transparent lenses much objective information which be
      cannot detected through naked eye observation is obtainable. Furthermore, data
      obtained from the images are comparable because of their objectivity. Although
      the methodology seems to be rather sophisticated and is costly, the above
      advantages make it an important asset in this type of cataract research. For
      example, lens transparency changes with ageing can be indicated quantitatively
      from image analysis data.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7634998
TI  - Leisure time, sunlight exposure and cataracts.
AB  - Leisure time sunlight exposure is a small or insignificant portion of total
      sunlight exposure experienced by most people at high risk for cataract. Few
      studies have been undertaken to evaluate a possible causal relationship, and
      these have largely been in Western countries. Analyses of data from the National
      Health and Nutrition Examination Survey (1971-1972) failed to confirm a
      relationship between leisure time exposure and cataract, but suggested that total
      exposure to sunlight was significantly related to cataract. A case-control study
      of cataract in Iowa suggested that controls were more likely to have shielded
      their eyes from sunlight than cases. A study in Italy suggested a positive
      relationship between leisure time sunlight exposure and lens opacities. In the
      large population-based Beaver Dam Eye Study population, we evaluated estimates of
      sunlight exposure and cataracts. We did not find that more leisure time sunlight
      exposure was associated with lens opacities. However, in men, estimates of
      lifetime exposure to ultraviolet-B were associated with cortical cataract. In
      summary, there is evidence to suggest that sunlight exposure may be related to
      cataract in diverse populations. Leisure time sunlight exposure is probably
      responsible for a small portion of that exposure.

PMID- 7634997
TI  - Ocular effects of UV-B exposure.
AB  - Although an association between UV-B exposure and ocular damage has been long
      suspected, this relationship is still not well quantified. Cataract is the most
      significant ocular damage associated with UV-B exposure. Initial studies of the
      association between UV-B exposure and cataract were hampered by a lack of
      precision in the assessment of cataract and a failure to separate cataract types.
      With a few exceptions, most studies have not assessed individual ocular UV-B
      exposure but have used ambient levels or isolated behaviours. Ecologic studies
      show there is more cataract in sunny areas, but whereas ambient UV-B fluxes may
      change by a factor of 3 or 4 over the globe, individual behaviour can change
      ocular exposure in a given location by 20-fold or more. The Chesapeake Bay
      Watermen studies assessed individual ocular UV-B exposure and have shown a
      consistent relationship between exposure to UV-B and the risk of both cortical
      and posterior subcapsular cataract. However, further work to refine these
      findings is sorely needed.

PMID- 7634999
TI  - Cataract and latitude.
AB  - For many years, it has been suggested that exposure to sunlight, particularly its
      ultraviolet component, may be associated with an increased risk of senile
      cataract. This paper addresses 1) the physical and geographic variables that
      affect the entry of ultraviolet light in the eye; 2) the epidemiologic evidence
      that associates cataract with ultraviolet light exposure; and 3) the
      effectiveness of personal barrier protection (i.e. sunglasses and hats) in
      reducing ocular exposure to ultraviolet light. The epidemiologic evidence is
      drawn from studies in Australia, China, Tibet, and the United States. The U.S.
      evidence consists of data from the Maryland Watermen study and analyses of
      cataract surgery under the Medicare program which provides health insurance for
      nearly all Americans age 65 and over (30 million) and pays for 85% of the 1.3
      million cataract extractions performed annually in the U.S. Analysis of the
      Medicard data shown that, after controlling for age, sex, and race, and income of
      the population and also controlling for supply of ophthalmologists, optometrists,
      price of surgery and local practice costs, the strongest predictor of cataract
      surgery likelihood in a Medicare beneficiary is the person's latitude of
      residence. Latitude correlates directly with the UV-B content of sunlight,
      because the incident angle of the sun determines the atmospheric penetration of
      ultraviolet radiation. Data suggest that the probability of cataract surgery in
      the U.S. increases by 3% for each 1 degree decrease (i.e. more Southerly) in
      latitude.

PMID- 7635000
TI  - Assessment of epidemiological evidence that exposure to solar ultraviolet
      radiation causes cataract.
AB  - In this paper an assessment is made of the evidence that exposure to solar
      ultraviolet radiation is causally associated with cataract. The evidence is
      reviewed separately for cortical, nuclear and posterior subcapsular cataract. The
      assessment examines the consistency and magnitude of an association, the dose
      response relationship, supporting ecological data, and data from animal studies.
      Based on the assessment, it is concluded that there is sufficient experimental
      evidence that exposure to artificial sources of UV-B can cause cortical opacities
      in laboratory animals. However, there is only limited evidence that exposure to
      solar UV-B causes cortical opacities in humans. Similarly, there is only limited
      evidence that exposure to solar UV-B causes posterior subcapsular cataract in
      humans. The epidemiological evidence is consistent in suggesting that nuclear
      cataracts are not causally associated with exposure to solar UV-B.

PMID- 7635001
TI  - UV-B as a pro-aging and pro-cataract factor.
AB  - One of the functions of the human lens is filter light between 300-400 nm from
      reaching the retina. The lens is therefore continually under photooxidative
      stress. In the young lens the primary absorbing species is the O-beta glucoside
      of 3-hydroxykynurenine (3-HKG) which has a maximum at 365 nm. Photophysical
      studies have demonstrated that absorptions by this compound in the short term are
      relatively benign to the lens, but in the long term can lead to the photochemical
      loss of 3-HKG with the concomitant yellowing of lens proteins. It will be
      proposed that part of this yellowing is due to the photochemically induced
      attachment of 3-HKG to lens proteins. The yellowing of lens proteins leads to a
      drastic increase in the number of photons absorbed by the lens. This, along with
      the age-related losses of antioxidants such as GSH will increase the
      photooxidative stress on the lens. Considering the foregoing and various
      epidemiological, model and biochemical studies, it can be concluded that light is
      most likely one of the causative factors in cataractogenesis.

PMID- 7635003
TI  - Aspirin to prevent heart attack or stroke.
AB  - Each year in the United Kingdom about 250,000 people die from acute myocardial
      infarction, other ischaemic heart disease or stroke. Many will already have
      evidence of established vascular disease that predisposes to such an event--such
      as angina, peripheral vascular disease, atrial fibrillation, transient ischaemic
      attacks or a previous myocardial infarction or stroke. Others will have risk
      factors such as hypertension, diabetes mellitus or hyperlipidaemia, but the
      stroke or heart attack is the first evidence of established vascular disease.
      Aspirin was first discovered to have antiplatelet properties 30 years ago and
      since then many randomised clinical trials have sought to determine whether it
      (or other antiplatelet agents) can protect patients from heart attack or stroke.
      In this article we review the evidence and update our earlier conclusions on
      stroke, myocardial infarction, and unstable angina, arguing that aspirin should
      be widely used to reduce cardiovascular morbidity and mortality in certain high
      risk patients.

PMID- 7635004
TI  - Medicines without an NHS prescription.
AB  - In the UK last year approximately 4.25 billion pounds was spent on medicines.
      About 80% of this went on prescribed drugs provided on the NHS. The remainder was
      spent on medicines prescribed privately and those bought over the counter (OTC)
      without prescription. In this article we consider OTC medicines and discuss how
      doctors can advise patients about the 500 or so products that cost less than the
      prescription charge (currently 4.25 pounds per item).

PMID- 7635002
TI  - The untenability of the sunlight hypothesis of cataractogenesis.
AB  - The excess prevalence of cataract in third world countries led early this century
      to the hypothesis that sunlight causes cataract. The hypothesis, which ignored
      differences in diet, culture, poverty and prevalence of other diseases such as
      diarrhoea, received little support until about thirty years ago when biochemical
      studies were set up to explore the browning of lens proteins, which is a common
      feature of cataract on the Indian subcontinent. Initially these studies were
      encouraging in that exposure to sunlight caused some changes seen in cataractous
      lenses, but eventually the hypothesis was rejected because the first change in
      the laboratory was the destruction of tryptophan, but this was not found in brown
      cataract lenses. A brown nuclear cataract could not be produced artificially in
      the laboratory using sunlight or UV exposure. Exposure of laboratory animals has
      produced lens opacities, but in most experiments the doses required have also
      caused keratitis, conjunctivitis, iritis and inflammation. The cornea seems more
      sensitive than the lens, which is not surprising, as it gets the first chance to
      absorb damaging UV. The biochemical rejection of the hypothesis coincided with
      the re-start of the epidemiological studies. Most of these are simply latitude
      studies and are no more than a repeat of what was available sixty years ago. They
      do not help to find a cause. Two studies showed that cataract was less common at
      higher altitude in the Himalayas, but unfortunately led to opposing conclusions.
      On the basis of common knowledge that UV exposure was greater at higher altitude,
      the first altitude study led to the rejection of the sunlight
      hypothesis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7635005
TI  - Moclobemide for depression.
AB  - Moclobemide (Manerix--Roche), the first of a new class of antidepressant drugs,
      was launched in the UK last year. It is a reversible inhibitor of monoamine
      oxidase A, which the manufacturer claims is a "first line treatment for major
      depression". Is this claim justified?

PMID- 7635006
TI  - Long-term management of people with psychotic disorders in the community.
AB  - Since the 1950s the number of beds for inpatient psychiatric treatment in Britain
      has fallen by over 100,000, and many people with long-term mental illness now
      rely on community-based rather than hospital facilities. General practitioners
      have a key role to play in their care. This article discusses the organisation of
      care for adults with chronic psychotic disorders. We consider how primary care,
      community mental health teams and hospital psychiatric services need to work
      together to ensure reliable and effective care.

PMID- 7635007
TI  - Fluoroquinolones for the eye.
AB  - Two fluoroquinolone antibiotics, ciprofloxacin (Ciloxan-Alcon) and ofloxacin
      (Exocin-Allergan), are available in the UK as topical preparations for the eye.
      Ciprofloxacin eyedrops are licensed for the treatment of "corneal ulcers and
      superficial infections of the eye", and ofloxacin eyedrops for "external ocular
      infections (such as conjunctivitis and keratoconjunctivitis)". In the UK
      chloramphenicol is commonly recommended as the drug of first choice for the
      treatment of superficial bacterial eye infections. Do fluoroquinolone
      preparations offer any advantage over this or other established drugs?

PMID- 7635008
TI  - Treating hypertension in patients with diabetes mellitus.
AB  - Patients with diabetes mellitus are at increased risk of developing
      cardiovascular disease, and the risks are increased further in those who are also
      hypertensive. In patients in whom the two disorders coexist emphasis is placed on
      ensuring that blood pressure is brought down to normal (diastolic pressure below
      90mm Hg). However, the choice of antihypertensive drugs is not straightforward
      for example, some interfere with blood sugar control and others may reduce the
      risk of complications of diabetes. This article discusses the choices.

PMID- 7635009
TI  - Using medicines in school.
AB  - In most schools there will always be some children who need to take medicines
      during school hours. Usually the course of treatment lasts only days, but
      sometimes, and particularly for children at schools for those with special needs,
      treatment may be continuous. Arrangements for taking medicines during the day
      vary and in some schools have led to children being denied optimum treatment. In
      this article we discuss the problems surrounding the use of medicines in school
      and consider ways of resolving them.

PMID- 7635010
TI  - Diuretics for heart failure.
AB  - For over 25 years diuretics have provided the mainstay of treatment for patients
      with heart failure. They reduce symptoms in both acute and chronic failure,
      rarely need to be stopped because of unwanted effects and cost very little. The
      overall effect of diuretic therapy on long-term mortality is not known, but
      outlook is certainly improved when an ACE inhibitor is added. In this article we
      review the use of diuretics in the management of acute and chronic heart failure
      and consider how they should be integrated with ACE inhibition.

PMID- 7635012
TI  - Management of genital Chlamydia trachomatis infections.
AB  - Chlamydia trachomatis is a common cause of genital infection and can give rise to
      urethritis and epididymitis in men and cervicitis and pelvic inflammatory disease
      in women. However, most genital chlamydial infections do not produce symptoms and
      so may be spread unknowingly. This article discusses the diagnosis and treatment
      of infection and how the risk of spread may be reduced.

PMID- 7635011
TI  - Tramadol--a new analgesic.
AB  - Tramadol (Zydol-Searle) is a centrally acting opioid analgesic newly marketed in
      the UK for use by mouth or injection. It is licensed for the prevention and
      treatment of moderate to severe pain. The manufacturer claims that it causes less
      constipation and respiratory depression than conventional opioids and that it
      offers a special "dual action". We examine the claims and consider the place of
      tramadol.

PMID- 7635014
TI  - Rational use of NSAIDs for musculoskeletal disorders.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) are used widely to relieve pain,
      with or without inflammation, in people with both acute and chronic
      musculoskeletal disorders. Over 20 NSAIDs, available in at least 40 different
      formulations, are listed in the British National Formulary. The efficacy of
      specific NSAIDs is hard to predict in individual patients, unwanted effects are
      common and some are serious. In this article we offer guidelines for the rational
      and safe use of NSAIDs for musculoskeletal disorders in adults.

PMID- 7635013
TI  - European Medicines Evaluation Agency and the new licensing arrangements.
AB  - Since September 1971 the Medicines Act has provided the legal basis for
      controlling the manufacture, sale, supply and marketing of medicines in the UK.
      The law has been modified by Parliament and the incorporation of European
      directives, but until now its interpretation and implementation have remained
      matters for UK authorities. From 1 January 1995 the position changes with the
      establishment of the European Medicines Evaluation Agency (EMEA) and the
      introduction of marketing arrangements for medicines that will be binding across
      the European Union (EU). The EMEA, which will be based in London, will act as a
      coordinating centre, housing and servicing the Committee for Proprietary
      Medicinal Products (CPMP; equivalent to our Committee on Safety of Medicines),
      the body that will advise the European licensing authority (European Commission).
      The new arrangements will cover medicines and vaccines (including blood products
      and radiopharmaceuticals) for both human and veterinary use. This article
      outlines the workings of the new system and discusses how they might affect the
      provision of medicines for human use in the UK.

PMID- 7635015
TI  - Withdrawing a drug from the market.

PMID- 7635016
TI  - Dexamethasone for bacterial meningitis in children.

PMID- 7635017
TI  - Prevention and control of hepatitis A.
AB  - Until recently, protection against hepatitis A has depended on high standards of
      public health and hygiene, bolstered by selective passive immunisation of those
      at high risk of infection using human normal immunoglobulin (HNIG). The scope for
      prophylaxis changed in April 1992 with the introduction of a hepatitis A vaccine
      (Havrix--SmithKline Beecham), which offers active immunisation and so longer and
      more effective protection than HNIG. In this article we discuss the epidemiology
      of hepatitis A and the methods of prevention and control of the infection. We
      also appraise the vaccine and consider how it should be used.

PMID- 7635018
TI  - Norplant--a contraceptive implant.
AB  - Norplant, a progestagen implant designed to provide contraception for five years,
      was launched in the UK in October 1993. Almost 3 million women world wide are
      using it. The manufacturer claims that Norplant is "one of the most effective and
      practical forms of contraception for any woman who wants long-term reliability,
      convenience and the opportunity to change her mind". In this article we assess
      its use.

PMID- 7635019
TI  - Adrenaline for anaphylaxis.
AB  - Adrenaline has long been the mainstay of treatment for anaphylaxis, but it is
      still not clear how best to give it. It can be administered, by intramuscular or
      subcutaneous injection, intravenous injection or infusion or by inhalation from
      an aerosol. Some of these approaches lend themselves to self administration by
      patients outside hospital: others need to be given under direct medical
      supervision. This article discusses the choices.

PMID- 7635020
TI  - Treating moderate and severe pain in infants.
AB  - Attitudes to treating moderate to severe pain in infants have changed during the
      past 15 years. Previously, strong analgesia was often withheld because of worries
      about unwanted effects of the drugs in sick infants, and because it was
      mistakenly believed that very young infants do not feel or remember pain. The
      need to prevent and relieve pain in infants is now widely accepted. In this
      article we review pain relief in the very young, concentrating on the recognition
      and treatment of acute pain such as occurs with surgery, invasive procedures,
      injury or acute inflammation. A future article will discuss the assessment and
      relief of pain in older children.

PMID- 7635021
TI  - Fluticasone propionate for asthma prophylaxis.
AB  - Inhaled corticosteroids have an essential role in the management of many patients
      with asthma, improving control and reducing the need for oral corticosteroids.
      Used in conventional dosage inhaled corticosteroids are very safe; in high dosage
      systemic effects are more evident. Fluticasone propionate (Flixotide--Allen &
      Hanburys), a new inhalation corticosteroid, is promoted as being more potent than
      conventional preparations (beclomethasone dipropionate and budesonide) and less
      likely to cause systemic effects. Is this claim justified and what is the place
      of fluticasone propionate in asthma prophylaxis?

PMID- 7635022
TI  - Cough caused by ACE inhibitors.
AB  - Persistent dry cough is a common unwanted effect of angiotensin converting enzyme
      (ACE) inhibitors and the most frequent reason for the drug being stopped. This
      article reviews the incidence and aetiology of ACE inhibitor cough and considers
      its management.

PMID- 7635023
TI  - Gabapentin--a new antiepileptic drug.
AB  - Gabapentin (Neurontin--Parke-Davis) is a new antiepileptic drug. Like
      lamotrigine, which we reviewed 2 years ago, it is marketed for the add-on
      treatment of patients with partial or secondarily generalised (tonic-clonic)
      seizures that are inadequately controlled with standard antiepileptic drugs.

PMID- 7635024
TI  - Routine iron supplements in pregnancy are unnecessary.
AB  - Women commonly take iron supplements during pregnancy. Many feel tired when
      pregnant, commonly their haemoglobin concentrations fall and it is known that
      iron is taken up preferentially by the developing fetus. In such circumstances
      additional iron appears justified. However, scientific support for this approach
      is weak. In this article we ask whether the routine use of iron supplements
      alters the outcome for mother or child.

PMID- 7635025
TI  - Folic acid to prevent neural tube defects.
AB  - Neural tube defects such as spina bifida and anencephaly affect about 2000
      pregnancies in the UK each year, and 1600 of these end in termination or
      stillbirth. To help prevent these defects women are advised to take supplements
      of folic acid around the time of conception and in the early weeks of pregnancy.
      In this article we look at the issues surrounding the routine use of folic acid.

PMID- 7635026
TI  - Managing patients with gallstones.
AB  - In the UK 1 in 3 women and 1 in 5 men will at some time develop gallstones. At
      least two-thirds of those with gallstones have no symptoms, and most stones are
      detected during investigations for unrelated reasons or at necropsy. In this
      article we discuss the medical and surgical management of patients with
      gallstones.

PMID- 7635027
TI  - "Talking about drug treatments--who should say what to whom?"--the second DTB
      symposium.
AB  - Information about medicines is as important as the quality of the medicines
      themselves. Without sufficient, accurate and understandable information the
      doctor cannot decide on the best treatment regimen to offer and ultimately the
      patient cannot decide what treatment to accept. The second annual Drug and
      Therapeutics Bulletin symposium, held in March, considered the provision of
      information, its production and distribution, and the legal, ethical and
      professional codes by which it is shaped. These issues were addressed by Ian
      Dodds-Smith (legal aspects), Nick Barber (pharmacy matters), Bonnie Sibbald
      (communication between hospital and general practice), Barbara Altounyan (the
      media), David Dickinson and Marianne Rigge (consumers), Gwen Parr and Justin
      Greenwood (the pharmaceutical industry) and Joe Collier (provision of consensus
      advice). The audience also made important contributions.

PMID- 7635029
TI  - Risk of long-term complications of diabetes mellitus reduced by tight blood sugar
      control.

PMID- 7635030
TI  - Paclitaxel for ovarian cancer.
AB  - Paclitaxel (Taxol-Bristol-Myers Squibb) is the first of a new group of cytotoxic
      drugs, the taxanes. It is licensed for the treatment of patients with metastatic
      ovarian carcinoma "where standard, platinum-containing, therapy has failed". What
      is its place in treatment?

PMID- 7635031
TI  - Antibiotic gels for periodontal disease.
AB  - Periodontal disease is a major cause of tooth loss. The underlying pathology is
      inflammation caused by bacterial plaque affecting the supporting structures of
      the teeth. Conventional treatment involves mechanical debridement of calcified
      plaque (calculus) by the dentist combined with meticulous oral hygiene by the
      patient. A more recent approach is to apply antimicrobial drugs locally to the
      diseased gingival tissue after debridement. Two antibiotic preparations,
      minocycline 2% gel (Dentomycin-Lederle) and metronidazole 25% gel (Elyzol-Dumex),
      are now licensed for the treatment of patients with periodontal disease. Are
      these treatments an advance on conventional therapy?

PMID- 7635028
TI  - A mesalazine enema for ulcerative colitis.
AB  - Given by mouth, drugs based on 5-aminosalicylic acid (5-ASA) are often effective
      in inducing or maintaining remission in patients with ulcerative colitis. All of
      them depend on delaying the release of 5-ASA, so minimising its absorption in the
      small intestine and maximising delivery to the colon. With sulphasalazine (a
      chemical combination of 5-ASA and sulphapyridine) and olsalazine (a combination
      of two molecules of 5-ASA) cleavage of the azo bond by bacteria releases free 5
      ASA in the colon. Oral formulations of mesalazine (the approved name for 5-ASA
      when given alone as a drug) use various physical mechanisms to release the 5-ASA
      gradually during transit through the gastrointestinal tract. Mesalazine can now
      be administered directly to the colon as an enema (Pentasa-Yamanouchi Pharma).
      How effective is this method of administering mesalazine and does it have a
      specific place in therapy?

PMID- 7635032
TI  - Drug treatment of epilepsy.
AB  - Epilepsy is a common neurological disorder. As many as 1 in 20 of the general
      population have a fit at some time in their lives, and at any one time around
      200,000 people in the UK are taking antiepileptic drugs. On treatment at least
      two-thirds of patients are likely to be free of attacks and eventually almost two
      thirds are likely to be fit-free on no medication. In this article we review the
      drugs used to control epilepsy and consider how and when they can be withdrawn.

PMID- 7635033
TI  - Epilepsy and pregnancy.
AB  - A child born to a woman with epilepsy has an increased risk of malformation, and
      this risk is increased further if the mother is taking an antiepileptic drug. In
      the last issue of the Drug and Therapeutics Bulletin we discussed the use of
      antiepileptic drugs in the general population. Here we discuss their use in women
      who are pregnant or planning pregnancy.

PMID- 7635034
TI  - Acarbose for non-insulin-dependent diabetes mellitus.
AB  - Acarbose (Glucobay-Bayer) is the first in a new class of oral antidiabetic drugs,
      the alpha-glucosidase inhibitors. It is licensed for the treatment of patients
      with non-insulin-dependent diabetes mellitus (NIDDM), either as first-line
      therapy when dietary measures are insufficient, or as an adjunct to conventional
      oral therapy where glycaemic control is suboptimal. The manufacturer claims that
      acarbose "can achieve a new level of blood glucose control in diabetes". In this
      article we consider whether acarbose offers any real advance.

PMID- 7635035
TI  - Unlicensed uses for growth hormone.
AB  - Synthetic human growth hormone (GH) is licensed for the treatment of short
      stature in GH-deficient children and girls with Turner syndrome (gonadal
      dysgenesis). GH is now also being used to treat children with growth failure due
      to other causes, as replacement therapy in GH-deficient adults and as an anabolic
      drug in certain groups of non-GH-deficient adults. This article discusses these
      unlicensed uses.

PMID- 7635036
TI  - Warfarin or aspirin for non-rheumatic atrial fibrillation?
AB  - Atrial fibrillation (AF) predisposes to stroke, particularly in patients with
      rheumatic heart disease, congestive heart failure, arterial hypertension,
      diabetes mellitus or uncontrolled thyrotoxicosis. In those with rheumatic heart
      disease it is usual to give warfarin to reduce the incidence of stroke, although
      there has been no randomised controlled trial on which to base this approach.
      Whether patients with non-rheumatic AF should be anticoagulated was unclear when
      we tackled this subject five years ago. This article reviews the evidence from
      recent randomised controlled trials and considers whether anticoagulation with
      warfarin, or antiplatelet therapy with aspirin, should now be routine for
      patients with non-rheumatic AF.

PMID- 7635037
TI  - Lacidipine--a once-daily calcium antagonist for hypertension.
AB  - In our recent review of calcium antagonists for the treatment of patients with
      cardiovascular disease we concluded that most patients could be managed with
      formulations of one of the original calcium antagonists, verapamil, diltiazem or
      nifedipine. Experience is greatest with these drugs, and none of the newer
      alternatives appeared more effective or better tolerated. Lacidipine (Motens
      Boehringer Ingelheim) is the latest calcium antagonist to be marketed for the
      treatment of patients with mild to moderate hypertension. It is licensed for once
      daily use without the need for a modified-release formulation; in this respect it
      resembles amlodipine. The manufacturer of lacidipine claims that its gradual
      onset of action "cushions the fall in blood pressure" and "cushions against side
      effects".

PMID- 7635039
TI  - The NHS drugs budget: a report by the Commons Select Committee.
AB  - Last month the House of Commons Select Committee on Health published the results
      of its inquiry on "whether the measures introduced by the Government to control
      the NHS drugs budget are leading to more appropriate and cost effective use of
      drugs in terms of current NHS resources and future patient needs". Members (6
      Conservative, 4 Labour and 1 Ulster Unionist) heard evidence from professional
      and patient groups, drug companies, consumer representatives, individuals and the
      Minister for Health. The Committee, whose specialist advisers included the editor
      of the Bulletin, also received nearly one hundred written submissions.

PMID- 7635038
TI  - Cisplatin or carboplatin for ovarian and testicular cancer?
AB  - Carboplatin was introduced in 1986 as a less toxic alternative to cisplatin. When
      we reviewed the drugs seven years ago it was not clear whether carboplatin could
      replace cisplatin in the treatment of cancer, and the debate has continued. In
      this article we compare the two products for the treatment of ovarian and
      testicular cancer.

PMID- 7635040
TI  - Should general practitioners give thrombolytic therapy?
AB  - Thrombolytic therapy reduces mortality from acute myocardial infarction. Moreover
      the earlier thrombolytic therapy is given after the development of infarction the
      greater the benefit. It is usual to start thrombolysis only after the patient has
      been admitted to hospital. In this article we discuss whether thrombolytic
      therapy should be started by the GP.

PMID- 7635041
TI  - Immunosuppressive drugs and their complications.
AB  - Drugs that suppress the immune system are widely used. They are part of the
      treatment of patients with organ transplants, malignancy, and increasingly those
      with conditions such as psoriasis, rheumatoid arthritis, and liver and bowel
      disease in which inflammation is an aetiological factor. Because of the
      broadening indications for immunosuppressive drugs, and the prolonged survival in
      conditions for which they are being used, many patients on immunosuppression are
      now cared for in the community or seen in non-specialist hospitals, usually in
      close collaboration with a specialist. This article looks at five commonly used
      immunosuppressive drugs in turn (corticosteroids, cyclosporin, azathioprine,
      methotrexate, cyclophosphamide), discussing the main, non-infection, unwanted
      effects, ways to avoid them and what to do if problems arise. The management of
      infection is dealt with as a separate section.

PMID- 7635042
TI  - Surgical management of menorrhagia.
AB  - In the UK each year about 1 in 20 women aged 25-44 consult their GP because of
      heavy menstrual bleeding (menorrhagia). Treatment with drugs is often
      disappointing. In this article we discuss the surgical alternatives--hysterectomy
      and the newer, 'minimally invasive' techniques for endometrial ablation.

PMID- 7635045
TI  - Polydactylous limbs in Strong's Luxoid mice result from ectopic polarizing
      activity.
AB  - Strong's Luxoid (1stD) is a semidominant mouse mutation in which heterozygotes
      show preaxial hindlimb polydactyly, and homozygotes show fore- and hindlimb
      polydactyly. The digit patterns of these polydactylous limbs resemble those
      caused by polarizing grafts, since additional digits with posterior character are
      present at the anterior side of the limb. Such observations suggest that 1stD
      limb buds might contain a genetically determined ectopic region of polarizing
      activity. Accordingly, we show that mutant embryos ectopically express the
      pattern-determining genes fibroblast growth factor 4 (fgf-4), sonic hedgehog
      (shh), and Hoxd-12 in the anterior region of the limb. Further, we show that
      anterior mesoderm from mutant limbs exhibits polarizing activity when grafted
      into host chicken limbs. In contrast to an experimentally derived polydactylous
      transgenic mouse, forelimbs of homozygotes show a normal pattern of Hoxb-8
      expression, indicating that the duplication of polarizing tissue here occurs
      downstream or independently of Hoxb-8. We suggest that the 1st gene product is
      involved in anteroposterior axis formation during normal limb development.

PMID- 7635043
TI  - Coordinate expression of the three zona pellucida genes during mouse oogenesis.
AB  - The mammalian zona pellucida is an extracellular matrix that surrounds growing
      oocytes, ovulated eggs and early embryos. The mouse zona is composed of three
      sulfated glycoproteins: ZP1, ZP2 and ZP3. Each is critically involved in
      fertilization, the postfertilization block to polyspermy and protection of the
      preimplantation embryo. We have previously isolated cDNAs encoding mouse ZP2 and
      ZP3 and now report the isolation of a full-length cDNA encoding ZP1. Mouse ZP1 is
      composed of a 623 amino acid polypeptide chain with a signal peptide and a
      carboxyl terminal transmembrane domain, typical of all zona proteins. Sequence
      comparison demonstrate that mouse ZP1 is an orthologue of a rabbit zona protein,
      R55. The expression of R55 has been reported previously in both oocytes and
      granulosa cells. However, by northern analysis and in situ hybridization with 33P
      labelled antisense probes to each of the three mouse zona mRNAs, we have
      determined that the expression of each mouse zona gene is restricted to the
      oocyte. ZP2 transcripts, but not ZP1 or ZP3, are detected in resting (15 microns
      diameter) oocytes, and all three zona transcripts coordinately accumulate as
      oocytes begin to grow. Together they represent approximately 1.5% of the total
      poly(A)+ RNA in 50-60 microns oocytes. In the latter stages of oogenesis, their
      abundance declines and each zona transcript is present in ovulated eggs at less
      than 5% of its maximal level. No zona transcripts were detected above background
      signal in granulosa cells. We conclude that, in mice, the three zona pellucida
      genes are expressed in a coordinate, oocyte-specific manner during the growth
      phase of oogenesis. Our data support the hypothesis that the transcription of the
      zona genes is controlled, in part, by shared regulatory element(s).

PMID- 7635044
TI  - Cis-regulatory control of the SM50 gene, an early marker of skeletogenic lineage
      specification in the sea urchin embryo.
AB  - The SM50 gene encodes a minor matrix protein of the sea urchin embryo spicule. We
      carried out a detailed functional analysis of a cis-regulatory region of this
      gene, extending 440 bp upstream and 120 bp downstream of the transcription start
      site, that had been shown earlier to confer accurate skeletogenic expression of
      an injected expression vector. The distal portion of this fragment contains
      elements controlling amplitude of expression, while the region from -200 to +105
      contains spatial control elements that position expression accurately in the
      skeletogenic lineages of the embryo. A systematic mutagenesis analysis of this
      region revealed four adjacent regulatory elements, viz two copies of a positively
      acting sequence (element D) that are positioned just upstream of the
      transcription start site; an indispensable spatial control element (element C)
      that is positioned downstream of the start site; and further downstream, a second
      positively acting sequence (element A). We then constructed a series of synthetic
      expression constructs. These contained oligonucleotides representing normal and
      mutated versions of elements D, C, and A, in various combinations. We also
      changed the promoter of the SM50 gene from a TATA-less to a canonical TATA box
      form, without any effect on function. Perfect spatial regulation was also
      produced by a final series of constructs that consisted entirely of heterologous
      enhancers from the CyIIIa gene, the SV40 early promoter, and synthetic D, C, and
      A elements. We demonstrate that element C exercises the primary spatial control
      function of the region we analyzed. We term this a 'locator' element. This
      differs from conventional 'tissue-specific enhancers' in that while it is
      essential for expression, it has no transcriptional activity on its own, and it
      requires other, separable, positive regulatory elements for activity. In the
      normal configuration these ancillary positive functions are mediated by elements
      A and D. Only positively acting control elements were observed in the SM50
      regulatory domain throughout this analysis.

PMID- 7635046
TI  - Mutations in a novel gene, myoblast city, provide evidence in support of the
      founder cell hypothesis for Drosophila muscle development.
AB  - We have used mutations in the newly identified gene myoblast city to investigate
      the founder cell hypothesis of muscle development in Drosophila melanogaster. In
      embryos mutant for myoblast city the fusion of myoblasts into multinucleate
      muscles is virtually abolished. Nevertheless, a subset of the myoblasts develop
      specific muscle-like characteristics, including gene expression appropriate to
      particular muscles, migration to the appropriate part of the segment, correct
      position and orientation, and contact by motor neurons. We suggest that this
      subset of myoblasts represents the proposed muscle founder cells and we draw an
      analogy between these founder cells and the muscle pioneers described for
      grasshopper muscle development.

PMID- 7635047
TI  - The role of Hoxa-3 in mouse thymus and thyroid development.
AB  - Targeted disruption of Hoxa-3 results in a number of regionally restricted
      defects in tissues and structures derived from or patterned by mesenchymal neural
      crest. However, analysis of mutant embryos with injections of a carbocyanine dye
      or with molecular markers that label these cells indicates that neither the
      amount nor the migration patterns of this neural crest population are grossly
      affected. Therefore, it appears that the loss of Hoxa-3 affects the intrinsic
      capacity of this neural crest cell population to differentiate and/or to induce
      proper differentiation of the surrounding pharyngeal arch and pouch tissues. Hoxa
      3 mutant mice are athymic and show thyroid hypoplasia. Thymus development is
      first evident as an expansion of mesenchymal neural crest in the posterior part
      of the 3rd pharyngeal pouch. Prior to this expansion, a marked reduction in pax-1
      expression is observed in these cells in the mutant embryos. As pax-1 mutant mice
      also show thymic hypoplasia, these results suggest that Hoxa-3 may be required to
      maintain pax-1 expression in these cells and that the reduction of pax-1
      expression is part of the athymic teleology in Hoxa-3 mutant mice. The thyroid
      gland is formed from the fusion of two structures of separate embryonic origin,
      the thyroid diverticulum, which is formed from endodermal epithelium in the floor
      of the pharynx, and the ultimobranchial body, formed from mesenchymal neural
      crest in the 4th pharyngeal pouch. Both of these sites express Hoxa-3 and are
      defective in mutant mice. Often a vesicle is observed in mutant mice that is
      exclusively composed of calcitonin-producing cells, suggesting the persistence of
      an ultimobranchial body. Both aspects of the thyroid phenotype show variable
      expressivity among mutant animals, even on the two sides of the same mutant
      animal. This variability suggests the presence of a compensating gene or genes,
      whose utilization is stochastic. A reasonable candidate for providing this
      compensatory function is the paralogous gene Hoxb-3.

PMID- 7635048
TI  - How do sea urchins invaginate? Using biomechanics to distinguish between
      mechanisms of primary invagination.
AB  - The forces that drive sea urchin primary invagination remain mysterious. To solve
      this mystery we have developed a set of finite element simulations that test five
      hypothesized mechanisms. Our models show that each of these mechanisms can
      generate an invagination; however, the mechanical properties of an epithelial
      sheet required for proper invagination are different for each mechanism. For
      example, we find that the gel swelling hypothesis of Lane et al. (Lane, M. C.,
      Koehl, M. A. R., Wilt, F. and Keller, R. (1993) Development 117, 1049-1060)
      requires the embryo to possess a mechanically stiff apical extracellular matrix
      and highly deformable cells, whereas a hypothesis based on apical constriction of
      the epithelial cells requires a more compliant extracellular matrix. For each
      mechanism, we have mapped out a range of embryo designs that work. Additionally,
      the simulations predict specific cell shape changes accompanying each mechanism.
      This allows us to design experiments that can distinguish between different
      mechanisms, all of which can, in principle, drive primary invagination.

PMID- 7635049
TI  - Role of the proneural gene, atonal, in formation of Drosophila chordotonal organs
      and photoreceptors.
AB  - The Drosophila gene atonal encodes a basic helix-loop-helix protein similar to
      those encoded by the proneural genes of the achaete-scute complex (AS-C). The AS
      C are required in the Drosophila PNS for the selection of neural precursors of
      external sense organs. We have isolated mutants of atonal, which reveal that this
      gene encodes the proneural gene for chordotonal organs and photoreceptors. In
      atonal mutants, all observable adult chordotonal organs, and almost all embryonic
      chordotonal organs fail to form; all adult photoreceptors are missing. For both
      types of sense organ, this defect is already apparent at the level of precursor
      formation. Therefore it is a failure in the epidermal-neural decision process
      i.e. a proneural defect. The failure to form photoreceptors results in atrophy of
      the atonal mutant imaginal disc, due to apoptosis and lack of stimulation of
      division. Lack of photoreceptors should also eliminate signalling that arises
      from differentiating photoreceptors and is required for morphogenetic furrow
      movement in the wild-type eye disc. Nevertheless, a remnant morphogenetic furrow
      is still observed in the atonal mutant disc. This presumably reflects the process
      of furrow initiation, which would not depend on signals from developing
      photoreceptors.

PMID- 7635050
TI  - Progenitor cells of the adult human airway involved in submucosal gland
      development.
AB  - A bronchial xenograft model of the human airway was used to identify submucosal
      gland progenitor cells within the surface airway epithelium. Lineage analysis
      using recombinant retroviruses has demonstrated considerable diversity in the
      cellular composition of expanded clones within reconstituted xenograft airway
      epithelium. These findings provide evidence for the existence of multiple
      progenitors in the airway with either limited or pluripotent capacity for
      differentiation. Furthermore, the development of transgene-expressing submucosal
      glands was associated with a single subset of surface airway epithelial clones.
      This gland progenitor cell demonstrated two discernible characteristics
      consistent with the identification of an airway stem cell including: (1)
      pluripotent capacity for airway differentiation and (2) a two-fold higher
      proliferative rate than other observed clone types. The number of progenitor
      cells involved in gland development was also assessed by clonal analysis using
      alkaline phosphatase and beta-galactosidase transgenes. These studies
      demonstrated that more than one airway progenitor cell is involved in the initial
      stages of gland development. A second explanation for the high prevalence of non
      clonality in developing glands was suggested from three-dimensional
      reconstruction of transgene marked glands. These reconstruction experiments
      demonstrated that 27% of glands contained more than one duct to the surface
      airway epithelium. This observation suggests a novel mechanism of gland
      morphogenesis by which independently formed glands interact to join glandular
      lumens. Such a mechanism of glandular development and morphogenesis may play an
      important role in normal submucosal gland development and/or the progression of
      hypersecretory diseases of the adult human airway as seen in cystic fibrosis,
      chronic bronchitis and asthma. The identification of progenitor cells with the
      capacity to form submucosal glands has implications on the targets for gene
      therapy in cystic fibrosis.

PMID- 7635051
TI  - Two CDC25 homologues are differentially expressed during mouse development.
AB  - The cdc25 gene product is a tyrosine phosphatase that acts as an initiator of M
      phase in eukaryotic cell cycles by activating p34cdc2. Here we describe the
      cloning and characterization of the developmental expression pattern of two mouse
      cdc25 homologs. Sequence comparison of the mouse genes with human CDC25 genes
      reveal that they are most likely the mouse homologs of human CDC25A and CDC25B
      respectively. Mouse cdc25a, which has not been described previously, shares 84%
      sequence identity with human CDC25A and has a highly conserved phosphatase domain
      characteristic of all cdc25 genes. A glutathione-S-transferase-cdc25a fusion
      protein can hydrolyze para-nitro-phenylphosphate confirming that cdc25a is a
      phosphatase. In adult mice, cdc25a transcripts are expressed at high levels in
      the testis and at lower levels in the ovary, particularly in germ cells; a
      pattern similar to that of twn, a Drosophila homolog of cdc25. Lower levels of
      transcript are also observed in kidney, liver, heart and muscle, a transcription
      pattern that partially overlaps, but is distinct from that of cdc25b. Similarly,
      in the postimplantation embryo cdc25a transcripts are expressed in a pattern that
      differs from that of cdc25b. cdc25a expression is observed in most developing
      embryonic organs while cdc25b expression is more restricted. An extended analysis
      of cdc25a and cdc25b expression in preimplantation embryos has also been carried
      out. These studies reveal that cdc25b transcripts are expressed in the one-cell
      embryo, decline at the two-cell stage and are re-expressed at the four-cell
      stage, following the switch from maternal to zygotic transcription which mirrors
      the expression of string, another Drosophila homolog of cdc25. In comparison,
      cdc25a is not expressed in the preimplantation embryo until the late blastocyst
      stage of development, correlating with the establishment of a more typical G1
      phase in the embryonic cell cycles. Both cdc25a and cdc25b transcripts are
      expressed at high levels in the inner cell mass and the trophectoderm, which
      proliferate rapidly prior to implantation. These data suggest the cdc25 genes may
      have distinct roles in regulating the pattern of cell division during mouse
      embryogensis and gametogenesis.

PMID- 7635052
TI  - Stem cell defects in parthenogenetic peri-implantation embryos.
AB  - Mouse embryos containing only maternal chromosomes (parthenotes) develop
      abnormally in vivo, usually failing at the peri-implantation stage. We have
      analyzed the development of parthenote embryos by using an inner cell mass (ICM)
      outgrowth assay that mimics peri-implantation development. ICMs from normal
      embryos maintained undifferentiated stem cells positive for stage-specific
      embryonic antigen-1 and Rex-1 while differentiating into a variety of cell types,
      including visceral endoderm-like cells and parietal endoderm cells. In contrast,
      ICMs from parthenotes failed to maintain undifferentiated stem cells and
      differentiated almost exclusively into parietal endoderm. This suggests that
      parthenote ICMs have a defect that leads to differentiation, rather than
      maintenance, of the stem cells, and a defect that leads to a parietal endoderm
      fate for the stem cells. To test the hypothesis that the ICM population is not
      maintained owing to a lack of proliferation of the stem cells, we investigated
      whether mitogenic agents were able to maintain the ICM population in parthenotes.
      When parthenote blastocysts were supplied with the insulin-like growth factor-1
      receptor (Igf-1r) and insulin-like growth factor-2 (Igf-2), two genes not
      detectable in parthenote blastocysts by in situ hybridization, the ICM population
      was maintained. Similarly, culture of parthenote blastocysts in medium
      conditioned by embryonic fibroblasts and supplemented with the maternal factor
      leukemia inhibitory factor maintained the ICM population. However, once this
      growth factor-rich medium was removed, the parthenote ICM cells still
      differentiated predominantly into parietal endoderm.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7635053
TI  - Mammary epithelial cells undergo secretory differentiation in cycling virgins but
      require pregnancy for the establishment of terminal differentiation.
AB  - Postnatal development of the mammary gland begins during puberty with ductal
      proliferation and is completed at delivery with the appearance of secretory
      alveolar structures. Using endogenous milk protein genes and a WAP-lacZ reporter
      transgene, we show that the differentiation of alveolar cells is initiated in
      virgin mice in estrus in a limited number of cells. With the onset of pregnancy,
      the number of expressing cells and the cellular expression levels increase until
      full activity is reached at lactation. Milk protein genes are activated in a
      defined temporal sequence. WDNM1 and beta-casein are expressed early in pregnancy
      and increase during alveolar proliferation. WAP (whey acidic protein) and alpha
      lactalbumin are expressed later near the end of gestation, which is characterized
      by terminal differentiation of the mammary secretory phenotype. By in situ
      hybridization, we have established evidence for asynchrony in milk protein gene
      expression among alveolar cells showing large variations in the intensity of
      hybridization among adjacent cells. The asynchrony of maturation of epithelial
      cells within a given alveolus suggests that the genetic program leading to
      terminal differentiation is subject to local modulation. It is likely that these
      signals are manifest through various pathways including growth factors, the
      extracellular matrix or gene products specific to terminal differentiation such
      as WAP. We extended our analyses to WAP/WAP transgenic mice in which WAP is
      synthesized precociously and functional differentiation of alveolar cells is
      impaired. We found an altered expression pattern of milk protein genes, with a
      strong reduction of alpha-lactalbumin RNA. We conclude that the early production
      of WAP in WAP/WAP mammary glands disrupts the timing of gene activation leading
      to a premature termination of the differentiative program.

PMID- 7635054
TI  - Identification of a neurogenic sublineage required for CNS segmentation in an
      Annelid.
AB  - In embryos of leeches (phylum Annelida), metameric structures arise sequentially
      from a germinal plate comprising the descendants of five pairs of embryonic stem
      cells called teloblasts. It has been shown that transverse stripes of cells
      expressing ht-en (a homolog of engrailed, a Drosophila segment polarity gene),
      arise in the germinal plate prior to the appearance of segmental ganglia and
      that, in the main neurogenic lineage (derived from the N teloblasts), the stripe
      of cells expressing ht-en demarcates the boundary between prospective segmental
      ganglia. Previous lineage-tracing experiments had suggested that the clones of nf
      and ns primary blast cells in the N lineage are confined to within segmental
      borders. This conclusion was called into question by the observation that the
      cells expressing ht-en do not appear to be at the very posterior edge of the nf
      clone, from which they arise. To resolve this issue, we have injected individual
      primary blast cells with fluorescent lineage tracers; we find that cells in the
      nf clone actually straddle two adjacent ganglia. Moreover, using photoablation
      techniques, we find that the nf clone is required for proper morphogenesis of the
      segmentally iterated central nervous system (CNS).

PMID- 7635055
TI  - Dorsalization of the neural tube by the non-neural ectoderm.
AB  - The patterning of cell types along the dorsoventral axis of the spinal cord
      requires a complex set of inductive signals. While the chordamesoderm is a well
      known source of ventralizing signals, relatively little is known about the cues
      that induce dorsal cell types, including neural crest. Here, we demonstrate that
      juxtaposition of the non-neural and neural ectoderm is sufficient to induce the
      expression of dorsal markers, Wnt-1, Wnt-3a and Slug, as well as the formation of
      neural crest cells. In addition, the competence of neural plate to express Wnt-1
      and Wnt-3a appears to be stage dependent, occurring only when neural tissue is
      taken from stage 8-10 embryos but not from stage 4 embryos, regardless of the age
      of the non-neural ectoderm. In contrast to the induction of Wnt gene expression,
      neural crest cell formation and Slug expression can be induced when either stage
      4 or stage 8-10 neural plates are placed in contact with the non-neural ectoderm.
      These data suggest that the non-neural ectoderm provides a signal (or signals)
      that specifies dorsal cell types within the neural tube, and that the response is
      dependent on the competence of the neural tissue.

PMID- 7635056
TI  - The somatic-visceral subdivision of the embryonic mesoderm is initiated by dorsal
      gradient thresholds in Drosophila.
AB  - The maternal dorsal regulatory gradient initiates the differentiation of the
      mesoderm, neuroectoderm and dorsal ectoderm in the early Drosophila embryo. Two
      primary dorsal target genes, snail (sna) and decapentaplegic (dpp), define the
      limits of the presumptive mesoderm and dorsal ectoderm, respectively. Normally,
      the sna expression pattern encompasses 18-20 cells in ventral and ventrolateral
      regions. Here we show that narrowing the sna pattern results in fewer invaginated
      cells. As a result, the mesoderm fails to extend into lateral regions so that
      fewer cells come into contact with dpp-expressing regions of the dorsal ectoderm.
      This leads to a substantial reduction in visceral and cardiac tissues, consistent
      with recent studies suggesting that dpp induces lateral mesoderm. These results
      also suggest that the dorsal regulatory gradient defines the limits of inductive
      interactions between germ layers after gastrulation. We discuss the parallels
      between the subdivision of the mesoderm and dorsal ectoderm.

PMID- 7635057
TI  - Control of Drosophila adult pattern by extradenticle.
AB  - The homeobox gene extradenticle (exd) acts as a cofactor of the homeotic genes in
      the specification of larval patterns during embryogenesis. To study its role in
      adult patterns, we have generated clones of mutant exd- cells and examined their
      effect on the different body parts. In some regions, exd- clones exhibit homeotic
      transformations similar to those produced by known homeotic mutations such as
      Ultrabithorax (Ubx), labial (lab), spineless-aristapedia (ssa) or Antennapedia
      (Antp). In other regions, the lack of exd causes novel homeotic transformations
      producing ectopic eyes and legs. Moreover, exd is also required for functions
      normally not associated with homeosis, such as the maintenance of the
      dorsoventral pattern, the specification of subpatterns in adult appendages or the
      arrangement of bristles in the mesonotum and genitalia. Our findings indicate
      that exd is critically involved in adult morphogenesis, not only in the homeotic
      function but also in several other developmental processes.

PMID- 7635058
TI  - A functional analysis of 5', intronic and promoter regions of the homeotic gene
      proboscipedia in Drosophila melanogaster.
AB  - In Drosophila, the homeotic gene proboscipedia (pb) is required for the formation
      of the adult mouthparts. To determine the functional significance of putative pb
      regulatory DNA, we have performed an in vivo analysis of sequences upstream of
      and within pb using a series of minigenes. Additionally, we have initiated a
      dissection of pb's promoter and enhancer elements using lacZ reporter gene
      constructs. Our results establish that a conserved region located in the second
      intron is essential for proper formation of the adult mouthparts. A 0.5 kb
      fragment from this region was shown to direct lacZ expression in a pb pattern in
      both embryos and third instar labial discs when combined with a 600 bp pb basal
      promoter sequence. A 32 bp element contained within the 0.5 kb region functions
      as a labial disc enhancers for pb. Surprisingly, the conserved second intron pb
      enhancers do not function properly with a heterologous hsp70 promoter, suggesting
      that promoter-specific interactions occur at the pb locus. We also found
      redundant and cryptic enhancers in the large introns of pb that are not required
      for pb function. Finally, we demonstrate that the pb transcription unit does not
      require sequences upstream of -98 bp to provide pb function in the labial discs.
      Rather, pb's upstream DNA appears to contain negative regulatory DNA required for
      silencing PB accumulation in inappropriate domains of third instar imaginal
      discs. Thus, we have defined many of pb's cis-controlling sequences to an
      experimentally manageable size, thereby making this an attractive system for the
      discovery of transacting proteins and, consequently, for elucidating the
      mechanisms of homeotic gene regulation.

PMID- 7635059
TI  - Induction of dorsal mesoderm by soluble, mature Vg1 protein.
AB  - Mesoderm induction during Xenopus development has been extensively studied, and
      two members of the transforming growth factor-beta family, activin beta B and
      Vg1, have emerged as candidates for a natural inducer of dorsal mesoderm.
      Heretofore, analysis of Vg1 activity has relied on injection of hybrid Vg1 mRNAs,
      which have not been shown to direct efficient secretion of ligand and, therefore,
      the mechanism of mesoderm induction by processed Vg1 protein is unclear. This
      report describes injection of Xenopus oocytes with a chimeric activin-Vg1 mRNA,
      encoding the pro-region of activin beta B fused to the mature region of Vg1,
      resulting in the processing and secretion of mature Vg1. Treatment of animal pole
      explants with mature Vg1 protein resulted in differentiation of dorsal, but not
      ventral, mesodermal tissues and dose-dependent activation of both dorsal and
      ventrolateral mesodermal markers. At high doses, mature Vg1 induced formation of
      'embryoids' with a rudimentary axial pattern, head structures including eyes and
      a functional neuromuscular system. Furthermore, truncated forms of the activin
      and FGF receptors, which block mesoderm induction in the intact embryo, fully
      inhibited mature Vg1 activity. To examine the mechanism of inhibition, we have
      performed receptor-binding assays with radiolabeled Vg1. Finally, follistatin, a
      specific inhibitor of activin beta B which is shown not to block endogenous
      dorsal mesoderm induction, failed to inhibit Vg1. The results support a role for
      endogenous Vg1 in dorsal mesoderm induction during Xenopus development.

PMID- 7635060
TI  - Tangential migration of neurons in the developing cerebral cortex.
AB  - The mammalian cerebral cortex is divided into functionally distinct areas.
      Although radial patterns of neuronal migration have been thought to be essential
      for patterning these areas, direct observation of migrating cells in cortical
      brain slices has revealed that cells follow both radial and nonradial pathways as
      they travel from their sites of origin in the ventricular zone out to their
      destinations in the cortical plate (O'Rourke, N.A., Dailey, M.E., Smith, S.J. and
      McConnell, S.K. (1992) Science 258, 299-302). These findings suggested that
      neurons may not be confined to radial migratory pathways in vivo. Here, we have
      examined the patterns of neuronal migration in the intact cortex. Analysis of the
      orientations of [3H]thymidine-labeled migrating cells suggests that nonradial
      migration is equally common in brain slices and the intact cortex and that it
      increases during neurogenesis. Additionally, cells appear to follow nonradial
      trajectories at all levels of the developing cerebral wall, suggesting that
      tangential migration may be more prevalent than previously suspected from the
      imaging studies. Immunostaining with neuron-specific antibodies revealed that
      many tangentially migrating cells are young neurons. These results suggest that
      tangential migration in the intact cortex plays a pivotal role in the tangential
      dispersion of clonally related cells revealed by retroviral lineage studies
      (Walsh, C. and Cepko, C. L. (1992) Science 255, 434-440). Finally, we examined
      possible substrata for nonradial migration in dorsal cortical regions where the
      majority of glia extend radially. Using confocal and electron microscopy, we
      found that nonradially oriented cells run perpendicular to glial processes and
      make glancing contacts with them along their leading processes. Thus, if
      nonradial cells utilize glia as a migratory substratum they must glide across one
      glial fiber to another. Examination of the relationships between migratory cells
      and axons revealed axonal contacts with both radial and nonradial cells. These
      results suggest that nonradial cells use strategies and substrata for migration
      that differ from those employed by radial cells.

PMID- 7635061
TI  - Xwnt-8b: a maternally expressed Xenopus Wnt gene with a potential role in
      establishing the dorsoventral axis.
AB  - In amphibian embryos, establishment of dorsal-ventral asymmetry is believed to
      involve dorsal-ventral differences in vegetally derived mesoderm-inducing signals
      and/or differences in the competence of animal hemisphere (ectodermal) cells to
      respond to these signals. Previous studies have shown that certain Wnt proteins
      can generate an ectopic dorsal axis when misexpressed, and that they do so by
      modifying the response of ectodermal cells to inducers. None of these Wnt
      proteins are expressed at an appropriate time to do so in vivo. In this study, we
      describe the isolation and characterization of a full length cDNA for the Xenopus
      Wnt gene, Xwnt-8b, whose biological activity and expression pattern suggest that
      it may be involved in establishment of the dorsoventral axis. Both maternal and
      zygotic Xwnt-8b transcripts undergo alternative splicing to generate mRNAs which
      encode two different forms of Xwnt-8b protein. During early cleavage stages Xwnt
      8b transcripts are confined primarily to animal hemisphere blastomeres, while
      zygotically derived Xwnt-8b transcripts are restricted almost exclusively to a
      band of cells in the prospective forebrain of neurula and tailbud stage embryos.
      Ectopically expressed Xwnt-8b can completely rescue dorsal development of embryos
      ventralized by exposure to ultraviolet light, and can induce a complete secondary
      axis in wild-type embryos. Axis induction is observed only if Xwnt-8b is supplied
      prior to the onset of zygotic gene transcription. This biological activity,
      together with the presence of maternal Xwnt-8b transcripts in cells that will be
      induced to form the dorsal mesoderm, is consistent with the possibility that Xwnt
      8b may be the endogenous agent that establishes asymmetry in the response of
      ectodermal cells to mesoderm-inducing signals, thereby initiating dorsal
      development.

PMID- 7635063
TI  - Induction of prostatic morphology and secretion in urothelium by seminal vesicle
      mesenchyme.
AB  - Mesenchymal-epithelial interactions are essential for the development of the male
      reproductive tract. Tissue recombination experiments have been used to define the
      characteristics of these interactions. When mesenchyme, embryonic connective
      tissue, is recombined with epithelium from another organ an instructive induction
      may occur in which the developmental fate of the epithelium is altered.
      Instructive inductions are most common when the epithelium that is removed from
      the mesenchyme and the epithelium that is recombined with the mesenchyme are from
      the same germ layer. All of the mesenchyme of the male reproductive tract is of
      mesodermal origin. The epithelia of these organs are derived from either the
      mesodermal Wolffian duct epithelium or the endodermal urogenital sinus
      epithelium. Urogenital sinus mesenchyme can instructively induce bladder and
      urethral epithelium to form prostate (Donjacour, A. A. and Cunha, G. R. (1993)
      Endocrinol. 132, 2342-2350) and seminal vesicle mesenchyme can instructively
      induce epithelium from the ductus deferens and ureter (Cunha, G. R., Young, P.,
      Higgins, S. J. and Cooke, P. S. (1991) Development 111, 145-158) to form seminal
      vesicle. To see whether inductive interactions could occur across germ layers in
      this system, seminal vesicle mesenchyme, normally associated with a mesodermal
      epithelium, was recombined with epithelium from neonatal or adult bladder or
      urethra, which are of endodermal origin. The resulting tissue recombinants were
      analyzed histologically and by immunocytochemistry and western blotting with
      antibodies to prostatic and seminal vesicle secretory proteins. Full prostatic
      differentiation was observed in tissue recombinants made with seminal vesicle
      mesenchyme plus either adult or neonatal bladder or urethral epithelium.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7635062
TI  - Astroglial control of oligodendrocyte survival mediated by PDGF and leukemia
      inhibitory factor-like protein.
AB  - Programmed death and the identification of growth factors delaying this process
      in the oligodendrocyte lineage suggest that other cell types provide
      oligodendrogliotrophins. To determine their source, primary cultures of
      oligodendroblasts immunopurified from postnatal rat cerebrum were used to screen
      other cultured neural and non-neural cell types for the release of survival
      factors into a defined insulin-containing medium. In non-conditioned medium,
      oligodendroblasts died 1-2 days after undergoing terminal differentiation into
      oligodendrocytes, as defined by the onset of expression of galactocerebroside. In
      medium conditioned by astrocytes, unlike the other tested cell types,
      differentiated oligodendrocytes survived for weeks in a mature myelinogenic
      state. Survival was partially reduced by immunoabsorption of the medium with
      antibodies to platelet-derived growth factor and abolished by immunoabsorption
      with antibodies to leukemia inhibitory factor. By the same criterion, survival
      activity was not attributed to other astrocytic products, ciliary neurotrophic
      factor and basic fibroblast growth factor. Membrane ultrafiltration analysis
      indicated the activity corresponded to heat-labile protein smaller (M(r) = 10(
      30) x 10(3)) than native rat leukemia inhibitory factor (M(r) = 43 x 10(3)). The
      astrocytic stimulus was > 4-fold more efficacious than other known
      oligodendrogliotrophic cytokines, including ciliary neurotrophic factor,
      neurotrophin-3 and leukemia inhibitory factor itself, tested singly or in
      combination, and promoted survival additively with these agents. These findings
      suggest that astrocytes function as paracrine regulators of oligodendroblast and
      oligodendrocyte survival and that their effect is mediated initially by platelet
      derived growth factor and thereafter by a powerful cytokine related to leukemia
      inhibitory factor.

PMID- 7635065
TI  - Duels without obvious sense: counteracting inductions involved in body wall
      muscle development in the Caenorhabditis elegans embryo.
AB  - During the first four cleavage rounds of the Caenorhabditis elegans embryo, five
      somatic founder cells AB, MS, E, C and D are born, which later form the tissues
      of the embryo. The classical criterion for a cell-autonomous specification of a
      tissue is the capability of primordial cells to produce this tissue in isolation
      from the remainder of the embryo. By this criterion, the somatic founder cells
      MS, C and D develop cell-autonomously. Laser ablation experiments, however,
      reveal that within the embryonic context these blastomeres form a network of
      duelling cellular interactions. During normal development, the blastomere D
      inhibits muscle specification in the MS and the C lineage inhibits muscle
      specification in the D lineage. These inhibitory interactions are counteracted by
      two activating inductions. As described before the inhibition of body wall muscle
      in MS is counteracted by an activating signal from the ABa lineage. Body wall
      muscle in the D lineage is induced by MS descendants, which suppress an
      inhibitory activity of the C lineage. The interaction between the D and the MS
      lineage occurs through the C lineage. An interesting feature of these cell-cell
      interactions is that they do not serve to discriminate between equivalent cells
      but are permissive or nonpermissive inductions. No evidence was found that the C
      derived body wall muscle also depends on an induction, which suggests that
      possibly three different pathways coexist in the early embryo to specify body
      wall muscle, two of which are, in different ways, influenced by cell-cell
      interactions and a third that is autonomous. This work supplies evidence that
      cells may acquire transient states during embryogenesis that influence the
      specification of other cells in the embryo. These states, however, may not be
      reflected in the developmental potentials of the cells themselves. They can only
      be scored indirectly by their action on the specification of other cells in the
      embryo. Blastomeres that behave cell-autonomously in isolation are nevertheless
      subjected to cell-cell interactions in the embryonic context. Why this should be
      is an intriguing question. The classical notion has been that blastomeres are
      specified autonomously in nematodes. In recent years, it was established that at
      least five inductions are required to determine the AB descendants of C. elegans,
      whereas the P1 descendants have been typically viewed to develop more
      autonomously. It appears now that inductions also play a major role during the
      determination of P1-derived blastomeres.

PMID- 7635064
TI  - Interaction of the pelle kinase with the membrane-associated protein tube is
      required for transduction of the dorsoventral signal in Drosophila embryos.
AB  - Within the Drosophila embryo, tube and the protein kinase pelle transduce an
      intracellular signal generated by the transmembrane receptor Toll. This signal
      directs import of the rel-related protein dorsal into ventral and ventrolateral
      nuclei, thereby establishing dorsoventral polarity. We show by immunolocalization
      that tube protein associates with the plasma membrane during interphase. We also
      find that tube sequences required for signaling interact with pelle in a yeast
      two-hybrid assay. We demonstrate that fusion of the pelle catalytic domain to the
      transmembrane receptor torso is sufficient to induce ventral fates; this activity
      is independent of Toll or tube. Lastly, we find that fusion of the tube protein
      to torso also induces ventral fates, but only in the presence of functional
      pelle. We propose a model wherein tube activates pelle by recruiting it to the
      plasma membrane, thereby propagating the axis-determining signal.

PMID- 7635066
TI  - Regulation of mouse egg activation: presence of ryanodine receptors and effects
      of microinjected ryanodine and cyclic ADP ribose on uninseminated and inseminated
      eggs.
AB  - Sperm-induced activation of mammalian eggs is associated with a transient
      increase in Ca2+ concentrations thought to be derived from inositol 1,4,5
      trisphosphate-sensitive and -insensitive intracellular stores. Whereas the
      importance of inositol 1,4,5-trisphosphate-sensitive Ca2+ stores has been
      evaluated, the identity and role of inositol 1,4,5-trisphosphate-insensitive
      stores are poorly understood. To explore the role of the ryanodine-sensitive Ca2+
      store, we first used reverse transcription-polymerase chain reaction to identify
      transcripts of the ryanodine receptor in eggs and determined that transcripts for
      the type 2 and 3 receptor were present. Immunoprecipitation of radioiodinated egg
      extracts with an antibody that recognizes both type 2 and 3 receptors detected
      specifically a band of Mr = 520,000. Immunolocalization of the receptor(s) using
      laser-scanning confocal microscopy revealed that the receptor(s) was uniformly
      distributed in the cortex of the germinal vesicle-intact oocyte, but became
      asymmetrically localized to the cortex in a region apposed to the meiotic spindle
      in the metaphase II-arrested egg; this asymmetrical localization developed by
      metaphase I. The role of the ryanodine receptor in mouse egg activation was
      examined by determining the effects of microinjected ryanodine or cyclic ADP
      ribose on endpoints of egg activation in either uninseminated or inseminated
      eggs. Ryanodine induced the conversion of the zona pellucida glycoprotein ZP2 to
      its postfertilization form ZP2f in a biphasic concentration-dependent manner;
      nanomolar concentrations stimulated this conversion, whereas micromolar
      concentrations had no stimulatory effect. Cyclic ADP ribose also promoted the ZP2
      conversion, but with a hyperbolic concentration dependence. Neither of these
      compounds induced cell cycle resumption. Inhibiting the inositol 1,4,5
      trisphosphate-sensitive Ca2+ store did not inhibit the ryanodine-induced ZP2
      conversion and, reciprocally, inhibiting the ryanodine-sensitive Ca2+ store did
      not inhibit the inositol 1,4,5-trisphosphate-induced ZP2 conversion. Last,
      treatment of eggs under conditions that would block the release of Ca2+ from the
      ryanodine-sensitive store had no effect on any event of egg activation following
      fertilization. Results of these experiments suggest that although ryanodine
      receptors are present and functional, release of Ca2+ from this store is not
      essential for sperm-induced egg activation.

PMID- 7635067
TI  - Role of methylation in maintenance of positionally restricted transgene
      expression in developing muscle.
AB  - In transgenic mouse embryos, expression of a muscle-specific reporter, consisting
      of a chloramphenicol acetyltransferase gene linked to regulatory sequences from
      the rat myosin light chain 1/3 locus (MLC-CAT), is graded in developing axial
      muscles along the rostrocaudal axis and in cell cultures derived from these
      muscles. Here we demonstrate that maintenance of positional differences in MLC
      CAT transgene expression cannot be attributed to differences in the
      transcriptional competence of corresponding muscles. Rather, patterns of
      transgene expression are reflected in the extent of CpG demethylation of both
      MLC1 promoter and MLC enhancer sequences. Variations in reporter gene expression
      can be reconstituted by in vitro methylation of specific CpGs in transfected MLC
      CAT DNA. As the MLC-CAT transgene is activated during embryogenesis,
      demethylation of the MLC1 promoter lags behind that of the downstream MLC
      enhancer, which appears to be the initial target for epigenetic modification. In
      developing somites, demethylation of the transgenic MLC enhancer is not graded
      and therefore does not reflect early regional differences in MLC-CAT transgene
      expression patterns. These studies implicate selective methylation in the
      maintenance rather than in the establishment of transcriptional differences in
      developing muscles.

PMID- 7635068
TI  - Penile tumescence in the human fetus at term--a preliminary report.
AB  - The aim of this study is to reveal whether the penis per se actually becomes
      tumescent and flaccid, in time sequence, in the human fetus at term. We observed
      the fetal penis with real-time ultrasonography in 50 male human fetuses at 36-39
      weeks' gestation and measured the penile length once at a given time per 1-min
      epoch for each case during the 60-min window of examination. Thirty-eight were
      excluded due to a lack of continuous ultrasound visualization of the penis.
      Penile length changes were statistically analyzed for the remaining 12 fetuses
      using the 'least median of squares regression'. Penile length was seen to be
      significantly stratified into two groups: 22.5% at tumescence (group median =
      20.8 mm) and 77.5% at flaccidity (group median = 16.0 mm). Penile tumescence was
      found to occur at the following frequency during the given observation period:
      once in 41.7%, twice in 50.0% and three times in 8.3% with durations ranging from
      5 to 17 min. These findings indicate penile tumescence exists in the term fetus.
      The frequency and duration of penile tumescence are in good correlation with
      neonates.

PMID- 7635069
TI  - Correction for environmental water influx in measurement of milk volume intake by
      deuterium turnover in infants.
AB  - Measurement of milk volume intake (MVI) in infants is a useful tool for assessing
      nutritional intake. Current measurement techniques include test-weighting,
      weighting formula-bottles, and calculation of MVI from water turnover estimated
      isotopically. Test-weighing of breast-fed infants may disturb normal feeding
      behaviour and thus influence intake. Calculation of MVI from water turnover is a
      non-invasive measurement method and can be applied to all infants whether breast
      fed or formula-fed. The method requires correction for environmental water influx
      (EWI) which constitutes non-oral water intake. EWI has previously been
      investigated only in premature or malnourished infants. The correction factor for
      EWI was calculated by comparing MVI obtained from weighing formula-bottles and
      measured isotopically in 21 formula-fed infants at 12 weeks of age. The mean
      correction factor, by which total water intake should be adjusted to obtain oral
      water intake, was 0.937 (S.E. 0.017). The proportion of water intake derived from
      non-oral sources was therefore 6.3%.

PMID- 7635070
TI  - Meconium aspiration syndrome--prevention and treatment.
AB  - Meconium aspiration syndrome (MAS) is a common neonatal problem and, sadly,
      results in acute and chronic respiratory morbidity. Although meconium aspiration
      can occur prior to delivery even in the absence of labour, in many infants this
      condition could be prevented by appropriate suctioning at birth. More accurate
      prediction of high risk patients and greater use of amnioinfusion may further
      reduce the occurrence of MAS. In infants with severe respiratory failure both
      high frequency ventilation and extracorporeal membrane oxygenation have a role.
      The place for either steroid or exogenous surfactant therapy in MAS remains to be
      defined.

PMID- 7635071
TI  - Doppler velocimetry and behavioural state development in relation to perinatal
      outcome in pregnancies complicated by gestational diabetes.
AB  - Seventy-one pregnancies complicated by gestational diabetes and 100 healthy
      pregnancies were monitored on two occasions (between 27th-32nd and 33rd-36th week
      of gestation) by behavioural state analysis (1F coincidence; 2F coincidence) and
      umbilical artery Doppler velocimetry (UA) (Resistance Index, RI). The purpose of
      our study was to determine if the development of behavioural states and Doppler
      velocimetry: (1) differ between normal and gestational diabetic cases; (2) in
      gestational diabetic cases, are they related to the degree of abnormality of the
      maternal oral glucose tolerance test (OGTT)?; and (3) are they predictors of
      perinatal outcome? (i.e. emergency caesarean section; low Apgar scores;
      respiratory distress syndrome; neonatal hypoglycaemia and neurological
      abnormality in the neonate and/or at 4 months of age). Our findings suggest that:
      (1) results on behavioral state development and Doppler velocimetry were
      significantly different in gestational diabetic cases; (2) infants of women with
      gestational diabetes who are neurologically abnormal during the newborn period,
      had a poor development of coincidence 2F during fetal life and had neonatal
      hypoglycaemia more often than infants with a normal neurological outcome; (3) in
      cases with abnormal neurological outcome, the maternal diabetes was more severe
      than in those cases with normal outcome.

PMID- 7635072
TI  - Gestational diabetes mellitus and paradoxical fetal macrosomia--a case report.
AB  - Gestational diabetes mellitus (GDM) is associated with an increased rate of fetal
      macrosomia. We describe the outcome of two pregnancies complicated by GDM
      occurring 2 years apart in a normal-weight woman. Despite adequate maternal blood
      glucose control during gestation, both infants were markedly oversized at birth
      (birth weight and length exceeded normal means by 3 and 2 S.D., respectively).
      The placental weights were far above normal. At birth, the siblings shared the
      typical appearance of a diabetes fetopathy. The first one developed transient,
      the second persistent neonatal hypoglycemia associated with hyperinsulinemia,
      that needed treatment with diazoxide for 2.5 months. Both infants normalized
      their growth rates during the following months; their psychomotor development
      assessed at 2 years and at 9 months of age, respectively, was normal. During the
      last trimester of the second pregnancy, the plasma concentration of placental
      lactogen (PL) increased to a very high level (19 micrograms/l). The maternal
      early insulin response to glucose increased significantly with gestation and was
      much above that in the non-pregnant state. This rise in insulin response could
      not compensate for the concomitant decrease in insulin sensitivity as assessed by
      the minimal model according to Bergman [2]. The pronounced fetal macrosomia
      described cannot be attributed to GDM only. We speculate that excess activity of
      lactogenic hormones like PL beside glucose contribute to exaggerated fetal beta
      cell function with growth acceleration and neonatal hypoglycemia. This hypothesis
      is in accordance with in vitro evidence indicating that PL may have an important
      role in the regulation of the maternal and fetal beta-cell mass and function.

PMID- 7635073
TI  - Spectral analysis of fetal heart rate in flat recordings.
AB  - Flat heart rate recordings may be observed in different fetal states such as
      chronic distress and sleep. Their visual analysis do not allow the distinction
      between these two states. We used spectral analysis to study the heart rate
      patterns in 25 fetuses. Two significant (P < 5 x 10(-5)) groups were apparent
      from the determination of the position of the maximum energy peak (PMEP) in the
      high-frequency band (0.20-0.50 Hz): a PMEP at about 0.20 Hz (group 1), and
      another around 0.30 Hz (group 2). The two groups did not differ in spectral
      density (SD). The outcome of neonates showed that group 1 fetuses made good
      progress and produced healthy neonates; whereas group 2 comprised cases of
      chronic fetal distress, or even death in utero, and neonatal distress. The
      significance of this difference in PMEP between fetal heart rate patterns in
      chronic distress and sleep is unclear. Studies combining the assessment of fetal
      movements and the determination of PMEP are planned.

PMID- 7635074
TI  - Establishment of normal values for flash visual evoked potentials (VEPs) in
      preterm infants: a longitudinal study with special reference to two components of
      the N1 wave.
AB  - To establish normal values for flash visual evoked potentials (VEPs) in the
      preterm period, we analyzed 356 records from 63 neurologically normal infants (26
      35 weeks gestation) followed longitudinally. Using both sleep and drowsy state
      recording within the same session and a mean of 5.7 weekly recording sessions per
      infant, we hypothesized that the prominent negative wave (N1) consisted of 2
      negative components, N1a (early) and N1b (late). This hypothesis could explain
      the previously reported variability in VEP indices. With a precise definition of
      the N1a peak, we were able to establish reference ranges for N1a peak latencies
      at various postmenstrual ages (PMA) which, unlike those previously reported, are
      narrow enough to be clinically useful. From a cross-sectional analysis we found
      that the N1a peak latency decreased with maturation at about 4.6 msec/week
      between 30 and 40 weeks PMA (P < 0.001). We also analyzed the N1 wave form and
      demonstrated its developmental maturation during this period. There were
      significant decreases in the amplitudes of both the N1a and N1b peaks with
      maturation (P < 0.001), but the decrease of the N1a amplitude was steeper than
      that of N1b. The N1 wave form changed from a wave in which the early peak (N1a)
      was higher than the late peak (N1b) into the reverse with N1b higher than N1a.
      This wave change may be related to developmental processes in the visual system.
      Longitudinal follow-up revealed that extra-uterine life may accelerate the
      maturation of the N1 wave form but has no effect on the decrease of the absolute
      values of peak latencies.

PMID- 7635075
TI  - Peri-rolandic and fronto-parietal components of scalp-recorded giant SEPs in
      cortical myoclonus.
AB  - Scalp topography of giant SEPs to median nerve stimulation was studied in 4
      patients with cortical myoclonus of various etiology. The positive peak (P30) at
      the contralateral parietal area was simultaneously accompanied by a negative peak
      at the frontal area (N30), and at least one of these two peaks was enhanced in 2
      patients. Another positive peak (P25) and a negative peak (N35) were also
      identified at the peri-rolandic area with different latency from P30 and N30,
      respectively, in all patients. N35 was enhanced in 3 patients, and P25 in 2
      patients. It is concluded that, as seen in normal subjects, tangential (P30-N30)
      and radial (P25 and N35) components of SEPs are most likely distinguishable in
      giant SEPs, and that either one or both of those components is enhanced in
      different ways depending on the patients.

PMID- 7635076
TI  - Generator locations of movement-related potentials with tongue protrusions and
      vocalizations: subdural recording in human.
AB  - Movement-related potentials (MRPs) associated with tongue protrusions and
      vocalizations were recorded from chronically implanted subdural electrodes over
      the lower perirolandic area in 7 patients being evaluated for epilepsy surgery.
      In 3 patients, tongue protrusions elicited a clearly defined, well localized slow
      negative Bereitschaftspotential (BP) at the motor tongue area, and a positive BP
      at the sensory tongue area. At the motor tongue area the negative BP was followed
      by a negative slope (NS') and a motor potential (MP), and at the sensory tongue
      area the positive BP and a positive reafferent potential (RAP) were seen but no
      NS' and MP could be identified. In the other 4 patients, tongue protrusions
      elicited positive BP, NS' and MP at the motor and sensory tongue area, and
      positive RAP at the sensory area. It was concluded that BPs, NS' and MPs are
      mainly generated in the motor cortex involving the crown as well as the anterior
      bank of the central fissure. The sensory cortex (areas 3a and 3b) also
      participated in the generation of BPs but to a lesser degree. Different degree of
      involvement of these multiple generators most likely explains the interindividual
      variability of polarity and distribution of the MRPs. RAPs most likely arise from
      primary sensory areas 1 and 2. Brain potentials were also recorded at the motor
      (2 patients) and sensory (2 patients) language areas, but no specific language
      related potentials could be identified. Evoked potentials to lip stimulation were
      investigated in 4 patients. In 3 patients, the responses at the sensory tongue
      area (P16, N21 and P30) had the same latency but opposite polarity to those at
      the motor tongue area. In the other patient, the responses (P16, N21 and P30) at
      the motor and sensory tongue areas were of the same polarity. The MRPs to tongue
      protrusions in those 4 patients revealed the same polarity relationship between
      the pre- and postcentral potentials. However, the maximal amplitude of evoked
      potentials and MRPs was seen at almost the same electrodes, suggesting that the
      main generators for these MRPs and evoked potentials must be located at
      contiguous areas in the anterior and posterior bank, respectively, of the central
      fissure.

PMID- 7635077
TI  - Subject-based P1 latency inter-root comparison, a method to evaluate P1 latency
      in scalp recorded somatosensory evoked potentials obtained with sensory nerve
      stimulation in the lower extremities.
AB  - The purpose of the present study was to establish a method that allows the
      general use of subject-based criteria to evaluate P1 latency in scalp recorded
      somatosensory evoked potentials obtained with stimulation of the sural (S1),
      superficial peroneal (L5) and saphenous (L4) nerves bilaterally. The nerves were
      stimulated at the same distance from the registration electrode. Two groups of
      normal nerve roots were studied: (1) nerve roots on both sides in 20 asymptomatic
      volunteers, and (2) neuroradiologically normal nerve roots on the asymptomatic
      side in 22 patients with unilateral sciatica. The results presented show that the
      P1 latencies after stimulation of the 6 different nerves in the same person can
      be regarded as equal. On this basis 2 criteria to evaluate P1 latency by within
      subject P1 latency inter-root comparison were defined. They were the difference
      between P1 latency of 1 registration and (1) that of any one of the other 5
      registrations and (2) the mean P1 latency of the other registrations. The
      variability of these subject-based criteria and the width of their reference
      limits were compared to those of the population-based criteria of height- and
      height-age-corrected P1 latency. This comparison showed that the use of within
      subject P1 latency inter-root comparison should enhance the ability to
      demonstrate small bilateral P1 latency prolongations at the same segmental level.

PMID- 7635078
TI  - Auditory brain-stem responses evoked by electrical stimulation of the cochlear
      nucleus in human subjects.
AB  - When auditory nerve function is lost due to surgical removal of bilateral
      acoustic tumors, a sense of hearing may be restored by means of an auditory brain
      stem implant (ABI), which electrically stimulates the auditory pathway at the
      level of the cochlear nucleus. Placement of the stimulating electrodes during
      surgical implantation may be aided by electrically evoked auditory brain-stem
      responses (EABRs) recorded intra-operatively. To establish preliminary standards
      for human EABRs evoked by electrical stimulation of the cochlear nucleus, short
      latency evoked potentials were recorded from 6 ABI patients who were either
      already implanted or undergoing implantation surgery. Neural responses were
      distinguished from stimulus artifact and equipment artifact by their properties
      during stimulus polarity reversal and amplitude variation. Other properties
      contributed to further identification of the evoked potentials as auditory
      responses (EABRs). The response waveforms generally had 2 or 3 waves. The peak
      latencies of these waves (approximately 0.3, 1.3, and 2.2 msec) and the brain
      stem localization of the region from which they could be elicited are consistent
      with auditory brain-stem origin.

PMID- 7635079
TI  - Neuromagnetic measurements of the human primary auditory response.
AB  - The spatio-temporal organization of the human primary auditory response (N19 and
      P30) was determined by analyzing magnetic fields from the right hemisphere evoked
      by monaural clicks to the left ear. The magnetic response consisted of peaks
      corresponding to electrical N19 (N19m) and P30 (P30m) within 40 msec after
      stimulation. However, the onset of electrical N19 occurred 5-9 msec earlier than
      that of the magnetic counterpart. Furthermore, the relative amplitude of N19 and
      P30 (N19/P30) was larger (more than 1) than that (about 0.5) of N19m and P30m
      (N19m/P30m). The findings suggest an additional contribution from a subcortical
      source for electrical N19. The estimated equivalent sources for N19m and P30m
      were localized at the postero-medial part of Heschl's gyrus (the primary auditory
      cortex). Furthermore, the dipole orientation of N19m was directed postero
      ventrally and that of P30m was in the opposite direction, which is compatible
      with the anatomy of the supratemporal primary auditory cortex. These results
      resolve a long standing controversy of cortical vs. subcortical structures as the
      generators of the N19.

PMID- 7635080
TI  - The origin of the human auditory brain-stem response wave II.
AB  - Auditory brain-stem responses (ABRs) were recorded from human subjects undergoing
      neurosurgical procedures which exposed the auditory nerve. Scalp recordings
      indicated that the latency of the negativity between waves I and II (In) and the
      latency of positive peak II (IIp) were shorter when the nerve was suspended in
      air than when the nerve was submerged in cerebrospinal fluid or saline, while
      earlier and later waves remained unaffected. These results could not be
      attributed to changes in stimulus or recording parameters or conduction velocity.
      Computational and somatosensory experimental evidence of stationary potentials
      generated by physical properties of the volume conductor, including changes in
      conductivity or geometry, are presented to develop a model of wave IIp
      generation. The results of this study suggest that wave IIp (and probably In) are
      manifestations of current flux asymmetries across conductivity boundaries created
      by the temporal bone-cerebrospinal fluid intradural space-brain-stem interfaces.
      The current flux asymmetries are generated as the propagating auditory nerve
      action potential crosses the conductivity boundaries. These results also indicate
      that the physical characteristics of the volume conductor and neural pathways
      must be considered when interpreting surface recorded evoked potentials.

PMID- 7635081
TI  - General ophthalmologic examination.
AB  - Caring for patients with eye emergencies will always challenge even the most
      experienced emergency clinician. The threat of loss of sight is anxiety provoking
      for patients and requires the physician to act in an organized and expeditious
      manner. By avoiding these pitfalls and examining each patient in a systematic and
      comprehensive fashion, the physician can ensure the best possible outcome. The
      ensuing articles describe the approach to diagnosing and treating significant eye
      emergencies in greater detail.

PMID- 7635082
TI  - Loss of vision.
AB  - Assessment of the patient with vision loss includes measurement of visual acuity,
      examination of the pupil, a finger-counting confrontation field examination, and
      an ophthalmoscopic examination. Opticokinetic testing is useful when functional
      blindness is being considered. A scheme is presented to use these findings to
      arrive at the anatomic level of this dysfunction. A differential diagnosis can
      then be generated. Some specific disorders causing vision loss are presented by
      anatomic location.

PMID- 7635084
TI  - Trauma to the globe.
AB  - Trauma to the globe is a common problem seen in the emergency department that may
      lead to significant permanent visual disability. Common causes of globe trauma
      include motor vehicle crashes, assaults, falls, and sports-related and
      occupational injuries. Rapid collection of accurate historical data, expedient
      physical examination, evaluation, and treatment are of paramount importance in
      preserving visual capacity. This article summarizes the initial diagnostic and
      therapeutic approach, important prognostic indicators, and delayed complications
      of the traumatized globe. Accurate diagnosis and proper disposition are vital in
      salvaging visual capacity.

PMID- 7635083
TI  - The red eye.
AB  - The red eye is a clinical problem encountered on a daily basis in most emergency
      departments. A careful history and focused ophthalmologic examination will lead
      to a correct diagnosis and proper therapy. The red eye without photophobia, pain,
      or visual disturbance is most commonly a result of conjunctivitis. The presence
      of any of these symptoms indicates a need to investigate for a more serious
      cause. Infectious causes of conjunctivitis should always be investigated, but
      allergies and hypersensitivity also should be considered if the history is
      appropriate. Emergency department treatment of the red eye should only include
      corticosteroids when the diagnosis is certain and ophthalmologic consultation is
      obtained.

PMID- 7635085
TI  - Ocular manifestations of systemic disease.
AB  - Systemic diseases can present with ocular manifestations to the emergency
      physician. Although most ocular findings serve to alert the physician to a
      possible ocular complication, many are different enough to aid the physician in
      making an obscure diagnosis. Knowledge of the characteristic ophthalmologic
      manifestations of systemic disease can aid the physician in diagnosing a
      particular disorder, limit the progression of more common diseases, and prevent
      further visual loss or blindness in patients with serious ophthalmologic
      complications.

PMID- 7635086
TI  - Lids, lacrimals, and lashes.
AB  - The eyelids and lashes serve to protect the globe from foreign bodies and
      injuries, and the lacrimal system protects the eyes through lubrication of the
      corneal and conjunctival surfaces. This article discusses trauma, infection,
      inflammation, anatomic abnormalities, and tumors that may result in serious
      complications interfering with normal eye function.

PMID- 7635087
TI  - Ophthalmologic therapeutics.
AB  - For the treatment of ocular disorders, the emergency physician has access to a
      variety of medications and delivery systems. This article focuses on topically
      applied ophthalmic medications: ointments and solutions, which are placed in the
      inferior conjunctival cul-de-sac, and hyperosmotic agents, which are administered
      parenterally. The indications, contraindications, potential side effects,
      mechanism of action, and dosage schedules for eight categories of ophthalmic
      agents are described. For most patients requiring ophthalmologic treatment in the
      emergency department, topical agents are highly efficacious, easy to administer,
      associated with few side effects, and inexpensive.

PMID- 7635088
TI  - Pediatric ophthalmology.
AB  - A wide variety of pediatric ophthalmologic diseases may present to the emergency
      physician. It is important for emergency physicians to know which diseases can be
      treated and which require urgent ophthalmologic intervention. Any asymmetry in a
      patient's ophthalmologic examination must be referred to a specialist for
      continuing care and definitive treatment. When identified early, strabismus,
      esotropia, or exotropia can be treated with significant benefit to the child's
      vision in the future. Abnormalities in size, shape, or color of the anterior
      portions of the eye are easily detected with inspection and may be indications of
      more serious illnesses such as conjunctivitis, glaucoma, cataracts, or tumors.
      These entities can be recognized by their distinguishing characteristics, and
      treatment can be initiated. Chlamydial and herpetic conjunctivitis, orbital
      cellulitis, posterior uveitis, and glaucoma are a few of the more urgent problems
      that may present to the emergency physician and should not be missed. A good
      history and careful examination will prevent the devastating effects of these
      diseases.

PMID- 7635089
TI  - Ophthalmologic procedures.
AB  - Step-by-step instructions for the most common and difficult ophthalmologic
      procedures that are performed in an emergency department. Foreign body removal,
      including rust rings, is explained with an emphasis on limiting further injury to
      the corneal epithelium and stroma. Patching, irrigation, contact lens removal and
      corneal culture techniques are explained. Three methods of assessing intraocular
      pressure are described.

PMID- 7635091
TI  - Specific binding of avidin to biotin containing lipid lamella surfaces studied
      with monolayers and liposomes.
AB  - The interaction of avidin (from egg white) with phospholipid (monolayer and
      bilayer) model membranes containing biotin-conjugated phospholipids has been
      studied. In the first part, using surface sensitive techniques (ellipsometry and
      surface plasmon resonance) we demonstrated that the nonspecific adsorption of
      avidin to phospholipid lamella could be abolished by adding an amount of Ca2+,
      Mg2+ or Ba2+ that led to an electrostatic interaction. The specific binding of
      avidin to lipid mixtures containing biotin-conjugated phospholipids was obviously
      composition dependent. The ratio 1:12 of a B-DPPE/DPPE mixture was found to be
      the optimum molar ratio. When we compared the results from the surface sensitive
      techniques with those from the electron micrographs of a two dimensional crystal
      of avidin (obtained in our laboratory), the optimum ratio was found to be
      determined by the effect of lateral steric hindrance. In the second part, we
      observed the pattern of the layers of fluorescently labeled phospholipid and
      adsorbed proteins with a home-made micro fluorescence film balance. The
      fluorescence images showed that avidin was preferentially bound to the receptors
      that were in the fluid domains. Further, with a sensitive fluorescence assay
      method, the effect of the phase behavior of liposomes on the specific binding of
      avidin was measured. This showed that avidin interacted with biotinlipid more
      weakly in the gel state liposome than in the liquid state liposome. The major
      conclusion was that the binding of avidin to a membrane bound model receptor was
      significantly restricted by two factors: one was the lateral steric hindrance and
      the other was the fluidity of the model membrane.

PMID- 7635090
TI  - Nystatin-, mycoheptin- and levorin-induced conductance in the membrane of frog
      skeletal muscle fibres.
AB  - The effects of the polyene antibiotics nystatin (2 x 10(-5)-10(-4) mol/l),
      mycoheptin (1.3 x 10(-6)-10(-5) mol/l) and levorin (10(-8)-5 x 10(-5) mol/l) on
      isolated frog skeletal muscle fibres and whole sartorius muscles of the frog have
      been investigated. Cation conductance was measured under current clamp conditions
      using a double sucrose-gap technique. Cation effluxes were studied by means of
      flame emission photometry. All three antibiotics increased the cation conductance
      and efflux rates; however, differences between the polyenes were found in the
      steady state values of induced cation transport at a given concentration. The
      values of both induced conductance gA infinity and efflux rate constants KA
      formed the following sequence: levorin > mycoheptin > nystatin, demonstrating a
      correlation with the order of antifungal activities. The dose-response curves of
      lg polyene-induced cation transport against lg of antibiotic concentration in our
      experiments had slope values which were much lower than those in bilayers: 1.7
      and 1.3 for nystatin and mycoheptin, respectively, whereas the aromatic heptaene
      levorin had an even smaller concentration dependence. The decline in the
      equilibrium conductance caused by nystatin- and mycoheptin removal was very fast
      (during the first minute tau = 0.74 and 2.39 min, respectively). In contrast,
      levorin-induced conductance was irreversible. It is proposed that the processes
      which limit the rate of channel formation are different in biological and model
      membranes.

PMID- 7635093
TI  - Seizures induced by homocysteine in rats during ontogenesis.
AB  - We studied the convulsant action of homocysteine in 211 immature and adult Wistar
      albino rats. Homocysteine elicited minimal, predominantly clonic, and major
      generalized tonic-clonic seizures at six different developmental stages, from 7
      days to adulthood. Nevertheless, some age-dependent differences in the seizure
      pattern were apparent. Minimal seizures in immature rats lasted < or = 20 min,
      thus representing an epileptic status, whereas in adult animals these seizures
      were much shorter, lasting only < or = 40 s. In addition, flexion seizures were
      observed in 7- and 12-day-old rats, only rarely in 15- and 18-day-old animals,
      and never in the 25-day-old and adult rats. ECoG recordings demonstrated a nearly
      isoelectric pattern during homocysteine-induced seizures in 7- and 12-day-old rat
      pups. In older rats, spikes or sharp waves were recorded, but precise
      electroclinical correlations were poor. The greater sensitivity of younger
      animals to kainic acid (KA) and N-methyl-D-aspartate (NMDA), as reported
      previously, was not evident in the case of homocysteine-induced seizures. This
      observation, together with a different behavioral pattern, suggests that
      homocysteine cannot be considered a simple agonist of the kainate or NMDA type of
      excitatory amino acid receptors. The exact mechanism of the convulsant action of
      homocysteine, both during development and in adulthood, remains to be clarified.

PMID- 7635094
TI  - Effects of pentobarbital on entorhinal tetanic responses and the progression of
      afterdischarges during the early course of amygdala kindling in rats.
AB  - We investigated the relationship between the progress of afterdischarges (AD) and
      the development of facilitated entorhinal tetanic responses by amygdala kindling
      stimulations in conscious and pentobarbital (PB)-treated rats. The entorhinal
      responses consisted of deep negative components and the following shallow
      positive components. The negative potential (mean +/- SE) reflecting excitatory
      synaptic activation in the test response evoked by a single stimulation (600
      microA) before kindling stimulations was greater in PB-treated rats (1.3 +/- 0.21
      mV, n = 6) than in conscious rats (0.5 +/- 0.08 mV, n = 9). The positive
      potential reflecting inhibitory synaptic activation in the test response was also
      greater in PB-treated rats (0.6 +/- 0.14 mV, n = 6) than in conscious rats (0.2
      +/- 0.04 mV, n = 9). The magnitude of the tetanic response was estimated as the
      area between the excitatory negative potential and the baseline in the averaged
      tetanic response during each kindling stimulation (10 Hz, 100 pulses). The
      magnitude of the tetanic response was significantly enhanced in association with
      the prolongation of AD duration in the conscious rats. In the PB-treated (50
      mg/kg intraperitoneally, i.p.) rats, enhancement of tetanic response was very
      slight and the progress of AD duration was prevented. There was a linear
      correlation (r = 0.9) between the magnitude of tetanic response and AD duration.
      These findings indicate that PB suppresses kindling-induced enhancement of
      excitatory synaptic activation in tetanic responses and that this enhancement is
      intimately related to the development of AD.

PMID- 7635092
TI  - Neonatal caffeine exposure and seizure susceptibility in adult rats.
AB  - Early developmental exposure to caffeine in rats results in changes in brain
      excitability that persist to adulthood. The mechanism of these alterations is
      unknown. To identify potential neurotransmitter systems involved, we exposed
      neonatal rats to caffeine and determined seizure thresholds for chemoconvulsants
      active at different CNS receptors in the adult animal. Rats were unhandled (NH)
      or received by gavage (0.05 ml/10 g) either vehicle (water) or caffeine (15-20
      mg/kg/day) for postnatal days 2-6. At age 70-90 days, each rat was infused
      intravenously (i.v.) with picrotoxin (PIC), bicuculline (BIC) [convulsants acting
      at the gamma-aminobutyric acid/benzodiazepine (GABA/BDZ) receptor],
      pentylenetetrazol [PTZ, possibly acting at both GABA/BDZ and N-methyl-D-aspartate
      (NMDA) receptors], caffeine (acting at adenosine receptors), strychnine (STR,
      acting at glycine receptors), or kainic acid (KA, acting at the NMDA receptor).
      Seizure thresholds were analyzed as a function of neonatal treatment and sex.
      Thresholds for caffeine, PTZ, PIC, and KA were increased as a function of
      neonatal caffeine exposure (p = 0.01, 0.02, 0.02, and 0.005, respectively). The
      thresholds for BIC and STR were not altered. There were also gender differences
      in seizure susceptibility. Thresholds for seizures produced by BIC, caffeine,
      PIC, and STR were higher in females (p = 0.005, 0.005, 0.001, and 0.0001,
      respectively), but were not different for seizures caused by PTZ. These results
      suggest that early developmental exposure to caffeine affects later seizure
      susceptibility. Moreover, some of these effects are gender specific.

PMID- 7635095
TI  - Kindling increases the sensitivity of rats to adverse effects of certain
      antiepileptic drugs.
AB  - Development of novel antiepileptic drugs (AEDs) requires determining the margin
      between the desired anticonvulsant effect and undesired adverse effects (AE)
      (therapeutic index). For this purpose, drug-induced "minimal neurological
      deficits" (e.g., motor dysfunctions) are commonly quantified by simple tests,
      such as the rotarod test, in normal, i.e., nonepileptic animals. However,
      increasing evidence shows that chronic brain dysfunction associated with epilepsy
      may increase susceptibility to the AE of certain AEDs, e.g., N-methyl-D-aspartate
      (NMDA) receptor antagonists. The increased AE potential of such investigational
      drugs can be predicted by using kindled rats instead of normal rodents in
      preclinical drug evaluation studies. In the present experiments, we wished to
      determine whether kindled rats also exhibit an altered susceptibility to
      neurological adverse effects of standard AEDs, i.e., carbamazepine (CBZ),
      phenobarbital (PB), valproate (VPA), and diazepam (DZP). Abecarnil, a novel
      benzodiazepine (BZD) receptor agonist, was included in the study for comparison.
      All drugs were administered in diverse doses in kindled and nonkindled rats, and
      all behavioral alterations were scored in the cage and open field. Furthermore,
      the rotarod test was used to detect and quantify motor impairment induced by drug
      treatments. Kindled rats were more susceptible than nonkindled rats to motor
      impairment (ataxia and/or rotarod failures) induced by high doses of AEDs,
      although differences were noted between the drugs tested. VPA was the only drug
      that induced stereotyped behavior; it was much more potent in this respect in
      kindled than nonkindled rats. Abecarnil did not differ substantially in its AE in
      either subgroup of animals. Our data indicate that epileptogenesis induced by
      kindling renders the brain more susceptible to certain AE of AEDs.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7635096
TI  - Distribution of unsaturated metabolites of valproate in human and rat brain-
      pharmacologic relevance?
AB  - The concentrations of valproate (VPA) and six of its pharmacologically active,
      unsaturated metabolites (E-delta 2-VPA, Z-delta 3-VPA, E-delta 3-VPA, E,E-delta
      2,3'-VPA, delta 4-VPA, and E-delta 2,4-VPA) were measured in serum and cortical
      brain samples from 24 patients undergoing epilepsy surgery. Collectively, the six
      metabolites were present at concentrations < 13% of VPA brain concentrations.
      Because the six unsaturated metabolites were present at such low brain
      concentrations, we concluded that these metabolites probably did not contribute
      significantly to the anticonvulsant effect of VPA. Results from a parallel
      pharmacodynamic study in rats in which VPA was administered three times daily for
      8 weeks supported this conclusion. Only three unsaturated metabolites (E-delta 2
      VPA, delta 3-VPA, E,E-delta 2,3'-VPA) were detected in rat brain. No correlation
      was observed between the time course of anticonvulsant effect [as measured by the
      timed intravenous pentylenetetrazol (PTZ) test] and the time course of VPA or
      metabolite concentrations in rat brain. Despite the structural similarity of VPA
      and its metabolites, striking differences were observed in their serum protein
      binding and blood-brain distribution properties. In the human brain, VPA and
      delta 4-VPA exhibited brain-to-free serum concentration ratios that were less
      than unity. In contrast, compounds with the double bond at the 2- or 3-position
      had brain:free concentration ratios that were much higher than unity. The
      structure-distribution relationship observed with VPA and its unsaturated
      metabolites suggested that these branched-chain fatty acids differ in their
      asymmetric transport across the blood-brain barrier (BBB).

PMID- 7635097
TI  - Northern epilepsy syndrome: clinical course and the effect of medication on
      seizures.
AB  - We describe the clinical course and treatment of 19 patients with the Northern
      epilepsy syndrome, an autosomal recessively inherited epilepsy with associated
      mental deterioration. The clinical course could be divided into three successive
      stages. The first stage continued from the onset of epilepsy until puberty.
      Seizures began at a mean age of 6.6 years and consisted predominantly of
      generalized tonic-clonic convulsions (GTC) and, transiently, also of complex
      partial seizures (CPS). Until puberty, seizure frequency increased in most
      patients from one attack in 1-2 months to one to two attacks weekly. Seizures did
      not respond to phenytoin (PHT) or carbamazepine (CBZ), were transiently
      controlled by valproate (VPA) and phenobarbital (PB), but were effectively
      treated only by clonazepam (CZP). Mental deterioration began 2-5 years after the
      onset of epilepsy and was most rapid before adulthood, a time when the seizures
      were also most frequent. The second stage is marked by fewer seizures, further
      mental deterioration, and less rapid progression. All patients were demented
      (I.Q. < 70) by age of 30 years. The first signs of motor clumsiness also appeared
      then. The third stage was one of permanent disability and usually began in middle
      age. Seizures were few, but the patients were clumsy and had marked equilibrium
      difficulties.

PMID- 7635098
TI  - Clobazam in long-term epilepsy treatment: sustained responders versus those
      developing tolerance.
AB  - Clobazam (CLB) is a structurally unique benzodiazepine (BZD) that has
      anticonvulsant activity in all types of refractory seizures. The main drawback to
      CLB, as to other BZDs, is the occurrence of tolerance. To date, there has been no
      way to predict which patients will develop tolerance. We compared clinical
      features and treatment variables between two groups of patients whose seizures
      were initially well controlled with CLB: patients with a sustained response and
      patients who developed tolerance. We retrospectively identified a group of 50
      very good responders from among 173 consecutive patients with uncontrolled
      epilepsy treated with CLB. Very good responders were defined as patients with >
      75% reduction in seizures after the addition of CLB who continued CLB treatment
      for at least 1 month. At a mean follow-up of 37.5 +/- 12.8 months, 25 patients
      continued to respond and 25 developed tolerance (mean follow-up 17.0 +/- 15.7
      months). Tolerance was defined as a relapse to a level > or = 50% of pre-CLB
      seizure frequency after an initial very good response for a minimum period of 1
      month, despite constant CLB dose and, when available, serum levels. There was no
      change in concomitant medication. Significant differences were noted between the
      two groups. The sustained response group had a shorter duration of epilepsy (mean
      16.5 vs. 24.5 years, p = 0.015), a greater proportion of individuals with a known
      etiology for their epilepsy (48 vs. 16%, p = 0.006), and higher CLB levels (0.50
      vs. 0.22 microM, p = 0.017), but no significant difference in N-desmethyl-CLB
      levels.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7635099
TI  - Reduction of plasma alanine aminotransferase during vigabatrin treatment.
AB  - In 9 drug-resistant patients with partial seizures treated with vigabatrin, gamma
      vinyl GABA (VGB), alanine aminotransaminase (ALAT) activity in plasma was
      significantly reduced. Comparison of in vitro with in vivo measurements led us to
      conclude that this reduction is mainly an in vivo phenomenon, perhaps due to
      cross-enzyme inhibition. The assessment of two biological variables linked with
      ALAT, glucose and alanine levels under fasting conditions, failed to show any
      significant metabolic alterations. VGB is an effective drug for partial epilepsy.
      Our observations do not suggest that reduced ALAT activity is of clinical
      concern.

PMID- 7635100
TI  - Thyroid and myocardial function after replacement of carbamazepine by
      oxcarbazepine.
AB  - We determined changes in serum concentrations of thyroid hormones during
      carbamazepine (CBZ) therapy during a 5-year prospective follow-up study of 20
      patients with newly diagnosed epilepsy. In addition, we evaluated the effects of
      replacing CBZ with oxcarbazepine (OCBZ) in 12 male patients with epilepsy in a 6
      month prospective follow-up study. Circulating thyroxine and free thyroxine
      levels decreased after 2-month CBZ treatment and remained at a low level during
      the 5-year follow-up. There were no associated changes in serum thyrotropin (TSH)
      concentrations. When CBZ was replaced by OCBZ, the function of the liver's P450
      enzyme system normalized, as shown by an increase in antipyrineT1/2, and a
      decrease in antipyrineCL. Serum total and free thyroxine levels increased, and
      thereafter serum TSH levels decreased. Indexes of diastolic heart function
      improved concomitantly, which may reflect subclinical hypothyroidism at the
      cellular level during CBZ treatment. We conclude that normal thyroid function can
      be restored in patients with epilepsy by replacing CBZ with OCBZ.

PMID- 7635101
TI  - Spectral EEG during short-term discontinuation of antiepileptic medication in
      partial epilepsy.
AB  - The effect of short-term discontinuation of antiepileptic drugs (AEDs) on
      spectral analysis of EEG background activity (spectral EEG) was studied in
      patients undergoing preoperative evaluation for epilepsy surgery. We also wished
      to clarify whether AED discontinuation would provide lateralizing evidence in
      spectral EEGs of patients with temporal lobe epilepsy (TLE). Spectral EEGs were
      performed in 15 patients receiving their regular medication regimen and again
      after a 1-week period during AED withdrawal. A subgroup of 9 patients who had
      previously undergone temporal lobectomies (TLE group) was studied separately. In
      this group, we evaluated the effect of preceding seizures on spectral EEG derived
      from temporal neocortical areas. In all patients, spectral EEG changes were
      detected even after a short-term AED withdrawal. The total amount of absolute
      delta activity was reduced and occipital peak frequency and relative alpha
      activity were increased as compared with baseline values. In TLE patients with
      habitual seizures occurring < 20 h before the spectral EEG recording,
      lateralization was correctly identified by the greater amount of absolute delta
      activity ipsilateral to the epileptogenic focus. Epileptic seizures are
      accompanied by subtle focal slowing in spectral EEG for a much longer period than
      has been assumed. In addition, postictal spectral EEG over the temporal lobes may
      have lateralizing value. Further studies in larger numbers of patients are needed
      to evaluate the role of spectral EEG in the preoperative evaluation of patients
      for temporal lobe surgery.

PMID- 7635102
TI  - Panic attacks as ictal manifestations of parietal lobe seizures.
AB  - Although most panic attacks appear to be primary psychiatric disturbances, some
      evidence suggests a biologic basis for panic disorder, possibly associated with
      temporal lobe dysfunction. Fear is a common affective change associated with some
      complex partial seizures (CPS) originating from the right temporal lobe. We
      describe a previously unreported association between panic attacks and seizures
      originating from the parietal lobe in 2 patients with right parietal lobe tumors.
      Intracranial monitoring documented correlations between the symptoms of fear and
      restricted regional parietal cortical discharges. Surgical resections of the
      lesions (one total, one subtotal) resulted in complete recovery or improvement.

PMID- 7635104
TI  - Nonphotosensitive video game-induced partial seizures.
AB  - We report a 9-year-old boy with a ring 20 chromosome anomaly whose complex
      partial seizures (CPS), presumably of frontal lobe origin, were often induced by
      playing video games. Neither photosensitivity nor pattern sensitivity was
      observed. An intensive video-EEG investigation showed that video games as well as
      mental calculation elicited rhythmic runs of bilateral high-voltage slow waves,
      which eventually evolved into ictal discharges. This case suggests that higher
      brain functions can be involved in seizure induction.

PMID- 7635103
TI  - Prognosis and treatment of seizures in children with acute lymphoblastic
      leukemia.
AB  - We reviewed the records of 127 consecutive pediatric patients with acute
      lymphoblastic leukemia (ALL) to determine the incidence, timing, etiologies, and
      recurrence rate of seizures in this population. Patients with ALL and seizures
      were identified retrospectively by review of the records of all pediatric ALL
      patients who were diagnosed and treated during the years 1983 through March 1993
      in a large tertiary-care hospital. Seventeen patients (13%) developed one or more
      seizures. In 16 patients, seizures occurred during antileukemic treatment, and in
      almost all of them seizures were related to intrathecal methotrexate (IT MTX) or
      subcutaneous L-asparaginase treatment. One patient who developed a seizure while
      not receiving chemotherapy had a history of cerebral infarctions. In 8 patients,
      (47%), the initial seizure episode was associated with a cerebral lesion. One or
      more seizures recurred in 6 patients. Four of these patients had an isolated
      recurrence, in 3 patients < or = 3 months and in 1 patient < or = 6 months after
      the initial event. Two patients (12%) with static encephalopathy and neurological
      deficits developed a chronic seizure disorder. There is a significant risk of
      acute symptomatic seizures in pediatric ALL patients. Most seizures in these
      patients occur during the acute treatment phase and are most frequently related
      to side effects of chemotherapy. The long-term recurrence risk is low; recurrence
      occurs most often in patients with evidence of cerebral structural lesions and
      neurological deficits. Long-term antiepileptic drug (AED) therapy should be
      restricted to such patients.

PMID- 7635105
TI  - 21st International Epilepsy Congress. Sydney, Australia, September 3-8, 1995.
      Abstracts.

PMID- 7635106
TI  - Human Tissue Monitoring and Specimen Banking: Opportunities for Exposure
      Assessment, Risk Assessment, and Epidemiologic Research. Research Triangle Park,
      North Carolina, 30 March-1 April 1993.

PMID- 7635108
TI  - Human tissue monitoring and specimen banking: opportunities for exposure
      assessment, risk assessment, and epidemiologic research.
AB  - A symposium on Human Tissue Monitoring and Specimen Banking: Opportunities for
      Exposure Assessment, Risk Assessment, and Epidemiologic Research was held from 30
      March to 1 April 1993 in Research Triangle Park, North Carolina. There were 117
      registered participants from 18 states and 5 foreign countries. The first 2 days
      featured 21 invited speakers from the U.S. Environmental Protection Agency, the
      Centers for Disease Control and Prevention, the National Institute of
      Environmental Health Sciences, various other government agencies, and
      universities in the United States, Canada, Germany, and Norway. The speakers
      provided a state-of-the-art overview of human exposure assessment techniques
      (especially applications of biological markers) and their relevance to human
      tissue specimen banking. Issues relevant to large-scale specimen banking were
      discussed, including program design, sample design, data collection, tissue
      collection, and ethical ramifications. The final group of presentations concerned
      practical experiences of major specimen banking and human tissue monitoring
      programs in the United States and Europe. The symposium addressed the utility and
      research opportunities afforded by specimen banking programs for future research
      needs in the areas of human exposure assessment, risk assessment, and
      environmental epidemiology. The third day of the symposium consisted of a small
      workshop convened to discuss and develop recommendations to the U.S.
      Environmental Protection Agency regarding applications and utility of large-scale
      specimen banking, biological monitoring, and biological markers for risk
      assessment activities.

PMID- 7635107
TI  - Estimating exposure and dose to characterize health risks: the role of human
      tissue monitoring in exposure assessment.
AB  - Exposure assessment is an integral part of health risk characterization. Exposure
      assessments typically address three critical aspects of exposure: the number of
      people exposed to the environmental toxicant, at specific concentrations, for the
      time period of interest; the resulting dose; and the relative contribution of
      important sources and pathways to exposure/dose. Because historically both "point
      of-contact" measurements and information about dose and related pharmacokinetic
      processes have been lacking, exposure assessments have had to rely on
      construction of "scenarios" to estimate exposure and dose. This could change,
      however, as advances in development of biologic markers of exposure and dose make
      it possible to measure and interpret toxicant concentrations in accessible human
      tissues. The increasing availability of "biomarkers," coupled with improvements
      in pharmacokinetic understanding, present opportunities to estimate
      ("reconstruct") exposure from measurements of dose and knowledge of intake and
      uptake parameters. Human tissue monitoring, however, is not a substitute for more
      traditional methods of measuring exposure, but rather a complementary approach. A
      combination of exposure measurements and dose measurements provides the most
      credible scientific basis for exposure assessment.

PMID- 7635109
TI  - Banking of human tissue for biomonitoring and exposure assessment: utility for
      environmental epidemiology and surveillance.
AB  - Human tissue banking could provide a tool to address a number of public health
      concerns. We can potentially use it to monitor trends in human exposures, serve
      as an early warning system for new environmental exposures, assess low-level
      exposures around hazardous waste and other point sources of pollutants, evaluate
      the effectiveness of regulatory programs, and study etiologies of diseases (e.g.,
      childhood cancer and birth defects) that are likely to be related to the
      environment. This article discusses opportunities to establish human tissue banks
      in connection with pre-existing public health surveillance programs for cancer
      and adverse reproductive outcomes. This is a cost-effective way to conduct
      surveillance and enhances the ability to carry out epidemiologic studies. The
      article also discusses ethical issues that are particularly important for public
      health practice. One is the issue of risk communication and the need to explain
      risks in a way that provides people with the information they need to determine
      appropriate action on the individual and community levels. Second is the issue of
      environmental justice. We recommend early involvement of communities that are
      likely to be involved in tissue-banking projects and full explanation of
      individual and group social risks from their participation.

PMID- 7635110
TI  - Measurement methods for human exposure analysis.
AB  - The general methods used to complete measurements of human exposures are
      identified and illustrations are provided for the cases of indirect and direct
      methods used for exposure analysis. The application of the techniques for
      external measurements of exposure, microenvironmental and personal monitors, are
      placed in the context of the need to test hypotheses concerning the biological
      effects of concern. The linkage of external measurements to measurements made in
      biological fluids is explored for a suite of contaminants. This information is
      placed in the context of the scientific framework used to conduct exposure
      assessment. Examples are taken from research on volatile organics and for a large
      scale problem: hazardous waste sites.

PMID- 7635111
TI  - Using biological monitoring to assess human exposure to priority toxicants.
AB  - Scientifically valid exposure assessment is crucial to risk assessment, risk
      management, and prevention of environmental disease. Scientists have used three
      tools to assess exposure: exposure history/questionnaire, environmental
      monitoring (including personal monitoring), and biological monitoring.
      Combinations of these tools usually provide the exposure information needed to
      meet objectives of human studies evaluating the exposure-health effect
      relationship. Biological monitoring is a capable exposure assessment tool that
      has provided important information used in public health decisions. We briefly
      describe how risk assessment and risk management decisions for lead, dioxin, and
      volatile organic compounds have substantially benefited from exposure information
      obtained from biological monitoring.

PMID- 7635112
TI  - The relationship between environmental monitoring and biological markers in
      exposure assessment.
AB  - The poor quality of traditional assessments of exposure has encouraged
      epidemiologists to explore biological monitoring in studies of chronic diseases.
      Yet, despite theoretical advantages, biomarkers have not been widely used in such
      applications. This article compares the general utility of a biomarker with that
      of the measurement of exposure per se. Points are illustrated with a longitudinal
      study of boat workers in which levels of styrene in the breathing zone and in
      exhaled air were compared to sister chromatid exchanges (SCEs) in peripheral
      lymphocytes. First, the linear relationship is explored between personal exposure
      and the levels of a biomarker in the cohort. A good fit to the straight-line
      relationship reflected by a correlation coefficient which is close to 1, such as
      observed with styrene in exhaled air (r2 = 0.83), suggests linear kinetics, that
      the appropriate route of exposure was measured by personal monitoring, small
      interindividual differences, adequate sample sizes, and a specific biomarker.
      However, a small correlation coefficient, as observed between SCEs and styrene
      exposure (r2 = 0.11), indicates that either kinetics were nonlinear or that more
      complex issues were involved with one or more of these factors. Second,
      environmental and biologic measurements are compared for use as independent
      variables in establishing a straight-line relationship between exposure and the
      health effect. If the ratio of the within-person to the between-person components
      of variance of the independent variable is large, then significant attenuation
      results when estimating the slope of the line.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7635113
TI  - Issues associated with the design of a national probability sample for human
      exposure assessment.
AB  - Data obtained from national probability sample surveys provide important
      information on the prevalence of various health conditions and distributions of
      physical and biochemical characteristics of the U.S. population. The sample
      design of a survey specifies how sampling from a designated population over a
      stated period is to be accomplished. A survey's analytical objectives and
      interests--in particular subpopulations--affect the sample design strategy.
      Selected subdomains of the population often must be oversampled so that estimates
      can be made with acceptable precision. This article addresses sample design
      considerations for a national probability sample for human tissue monitoring and
      specimen banking. Among the sampling issues addressed are the oversampling of
      special populations e.g., minority groups and at-risk groups such as low income
      or elderly persons; geographic coverage; and sample size considerations. The
      sample design for a major health survey, the Third National Health and Nutrition
      Examination Survey (NHANES III), is used to illustrate a complex, multistage
      probability sample design and to highlight some of the sampling issues discussed
      in this article.

PMID- 7635114
TI  - Considerations in the design of an environmental specimen bank: experiences of
      the National Biomonitoring Specimen Bank Program.
AB  - Since 1979 the National Institute of Standards and Technology (NIST) has been
      involved in environmental specimen banking activities as part of the National
      Biomonitoring Specimen Bank (NBSB). These activities have focused on the
      development of procedures for the collection, processing, analysis, and long-term
      storage of a variety of environmental specimens including: human liver, mussels
      and oysters, fish tissue (liver and muscle), marine mammal tissues (blubber,
      liver, and kidney), and marine sediments. The experiences of the NBSB can provide
      valuable information to assist in the design of new specimen bank efforts. Based
      on the experiences of the NBSB, the issues that should be addressed in the design
      and operation of a valid specimen bank program are presented.

PMID- 7635115
TI  - Ethical considerations, confidentiality issues, rights of human subjects, and
      uses of monitoring data in research and regulation.
AB  - Biomarkers are potentially powerful tools for use in research and regulation.
      Their derivation from biologic specimens collected from human subjects does,
      however, present many ethical implications. Ethical issues are relevant in almost
      each facet of human biomarker research studies: design, identification and
      recruitment of subjects, handling and use of the data, and interpretation and
      communication of results. Researchers also face a number of dilemmas when
      considering the use of human biologic specimens and new biomarkers. The mere fact
      that such markers are the result of measurements in human specimens gives the
      appearance of being more accurate than traditional sources of information such as
      questionnaires or environmental monitoring; yet, this may not always be the case.
      The meaning of the results of biomarker studies may be unclear because the
      purpose of the study is usually for research rather than clinical purposes. There
      generally are no established normal ranges for biomarkers and the interpretation
      of findings are often difficult. Researchers may not communicate these results to
      subjects or consider followup action because the task may be too difficult or
      undefined, or the reaction of the subject cannot be anticipated. A wide range of
      practices in this regard exists among researchers. Many questions remain
      unanswered about the use of biologic specimens. These include questions of
      ownership and access to specimens. Related to this is the question of whether
      specimens collected for one research purpose can be used for an entirely
      different research purpose. This is still an open question.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7635116
TI  - Ethical considerations in the design and execution of the National and Hispanic
      Health and Nutrition Examination Survey (HANES).
AB  - The purpose of this article is to describe some ethical considerations that have
      arisen during the design and implementation of the health examination surveys
      conducted by the National Center for Health Statistics of the Centers for Disease
      Control and Prevention. Three major areas of concern are discussed: sharing
      information from the study, banking and using banked tissue samples, and
      obligations for future testing of subjects. Specific concerns of sharing
      information include: when to inform, whom to inform, maintaining confidentiality,
      and how to inform individuals. Specific concerns of determining when sera will be
      banked and using banked samples include: depletion of samples for quality
      control, obtaining informed consent for unanticipated uses, access by others, and
      requests for batches of samples. Finally, specific concerns regarding future
      testing of subjects include: retesting for verification, retesting for
      interpretation, testing for different risk factors, and follow-up. Although
      existing surveys can provide experience or even suggest guidelines, the
      uniqueness of any new survey will generate unique ethical problems, requiring the
      careful formulation of unique solutions.

PMID- 7635117
TI  - Monitoring human tissues for toxic substances: a follow-up to the National
      Academy of Sciences (NAS) report.
AB  - In 1991, the National Academy of Sciences (NAS) published a report, Monitoring
      Human Tissues for Toxic Substances, which presented a summary of thinking about
      the banking of human tissue specimens at the time the report was completed. The
      present article summarizes the findings and recommendations in the NAS report.
      Events have moved very rapidly since that time, but some history may be helpful
      in understanding how we have come to where we are today.

PMID- 7635118
TI  - Experiences of the Janus Serum Bank in Norway.
AB  - The ongoing JANUS project was started in 1973. The serum bank comprises 424,938
      serum samples consolidated from 293,692 donors. The specimens are stored at -25
      degrees C. From 1 to 13 consecutive samples are available from each donor. Up to
      October 1993 about 14,000 of the donors had developed some form of cancer. Frozen
      serum samples collected from a few months to 19 years prior to clinical
      recognition of their disease are available for research purposes. The principle
      aim of the JANUS project is to search in the premorbid sera for chemical,
      biochemical, immunological or other changes that might be indicative of cancer
      development at early stages. Gas chromatography-mass spectrometry and two
      dimensional protein electrophoresis have been used to evaluate the stability of
      the frozen sera. Some recent findings are: CA-125 may be elevated months prior to
      the diagnosis of ovarian cancer; serum thyroglobulin may be a preclinical tumor
      marker in subgroups of thyroid cancer; low levels of selenium in serum reflects
      increased risk of thyroid cancer; raised antibodies in serum against Epstein-Barr
      virus is a risk factor for development of Hodgkins disease; prostate-specific
      antigen may be elevated years prior to clinical diagnosis of prostate cancer; and
      linoleic acid in serum phospholipids is inversely related to breast cancer risk.
      The serum bank is, in principle, suitable for environmental studies, e.g., human
      exposure assessment. The steering committee of the JANUS project is open to
      suggestions for collaborative research on this topic.

PMID- 7635119
TI  - The priority toxicant reference range study: interim report.
AB  - The relationship between human exposure to environmental toxicants and health
      effects is of utmost interest to public health scientists. To define this
      relationship, these scientists need accurate and precise methods for assessing
      human exposure and effects. One of the most accurate and precise means of
      assessing exposure is to measure the level of the toxicant or its primary
      metabolite in a biologic specimen; this has been defined as measuring the
      internal dose. This measurement must be quantitative to best study the dose
      response relationship. Pertinent questions asked during an exposure assessment
      include "How do the levels of a given toxicant in a particular population compare
      with the levels of that toxicant in other populations?" and "What is the
      prevalence of exposure to that toxicant in other populations?" To answer these
      questions for two chemical classes of environmental toxicants, we developed state
      of-the-art analytic methods and then applied them to measure the levels of 44
      environmental toxicants in biologic specimens from 1000 United States residents
      who participated in the Third National Health and Nutrition Examination Survey
      (NHANES III). These 1000 people are a cross-sectional subset of the NHANES III
      population and were selected from urban and rural communities in four regions of
      the United States; all were between 20 and 59 years of age. This subset is not a
      probability-based sample.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7635120
TI  - The role of specimen banking in risk assessment.
AB  - The risk assessment process is described with a focus on the hazard
      identification and dose-response components. Many of the scientific questions and
      uncertainties associated with these components are discussed, and the role for
      biomarkers and specimen banking in supporting these activities are assessed.
      Under hazard identification, the use of biomarkers in defining and predicting a)
      biologically adverse events; b) the progression of those events towards disease;
      and c) the potential for reversibility are explored. Biomarker applications to
      address high-to-low dose extrapolation and interindividual variability are
      covered under dose-response assessment. Several potential applications for
      specimen banking are proposed.

PMID- 7635121
TI  - Recent advances in measuring exhaled breath and estimating exposure and body
      burden for volatile organic compounds (VOCs).
AB  - An improved portable breath measurement method has been developed that allows 1
      min sampling times. The equipment has been successfully tested in field and
      chamber studies. Results of these studies suggest that breath levels following
      known exposures are predictable and reproducible across a small number of
      volunteers. The residence times in the body and the distribution in body
      compartments of several common air toxics have been determined. A simple four
      compartment linear model is capable of fitting the observed data. The main
      parameters of the model include the fraction f of the parent compound exhaled
      under steady-state conditions and the residence times tau i, in the tau ith
      compartment. The values of these parameters for several VOCs and for the four
      body compartments (blood, vessel-rich tissues, vessel-poor tissues, and fat) are
      provided.

PMID- 7635123
TI  - Improving interface quality: an investigation of human-computer interaction task
      learning.
AB  - User learning is of critical importance in evaluating interface usability (and in
      turn interface quality). The focus of this research in on interface learnability,
      where a stochastic model represents the learning process required for successful
      completion of human-computer interaction tasks. The parameter used to quantify
      learning is a learning rate. Of interest here is the validation of learning rate
      as a measure of interface quality. Learning rate was validated against two
      traditional measures of interface quality: task completion time, and error
      frequency. SuperCard, a Macintosh project utility, provided an empirical learning
      environment in which 32 participants learned 16 fundamental SuperCard tasks.
      Results of correlation analyses suggested the usefulness of learning rate as an
      indicator of interface quality. Our learning rate analysis identified four tasks
      presenting learning difficulties. (Analysis of task completion times identified
      two of these four tasks, and error frequency analysis identified one). Learning
      rate data captured all of the information available from the two traditional
      interface quality measures and identified two tasks disregarded by them.
      Incorporating learning rates in the interface evaluation process precludes time
      intensive video tape analysis typically required by more traditional interface
      quality measures.

PMID- 7635122
TI  - Adipose tissue as a medium for epidemiologic exposure assessment.
AB  - In the United States, adipose tissue is rarely used as a medium for assessment of
      prior exposures in epidemiologic studies. Adipose tissue aspirations are in
      general less invasive and carry less risk than phlebotomy. Tissue samples can be
      analyzed for a wide number of epidemiologically important exposures. Beyond
      reflecting long-term energy balance, this tissue offers a relatively stable depot
      of triglyceride and fat-soluble substances, such as fat-soluble vitamins, and
      pesticides. As a tissue it represents the greatest reservoir of carotenoids in
      the body. Halogenated hydrocarbons may be measured in concentrations of hundreds
      fold greater than those in blood of the same individuals. The composition of
      adipose tissue also reflects the long-term dietary intakes of a number of
      essential fatty acids. The turnover times of all of these substances in adipose
      tissue remain under-researched. Sampling and storage of adipose tissue,
      homogeneity of sampling sites, turnover times, and the effects of diet, age,
      gender, race, hormones, and disease on adipose tissue composition are discussed
      in this review of current knowledge about adipose tissue stability. Experience in
      the use of adipose tissue sampling in epidemiologic studies in various countries
      has shown that it is simple to conduct, requires little training, carries little
      risk, and does not result in excessive participant refusal.

PMID- 7635124
TI  - The influence of perceptual 'set' on the detection of motorcyclists using daytime
      headlights.
AB  - Voluntary daytime headlight use by the majority of motorcyclists might endanger
      those not using lights: it has been suggested that drivers might scan for lights
      rather than for motorcyclists per se. Two experiments are described that
      attempted to investigate this issue in the laboratory. Subjects had to decide as
      rapidly as possible whether or not a motorcyclist was present in each of a series
      of slides depicting traffic. Experiment 1 showed that headlight-using
      motorcyclists were more quickly detected than unlit motorcyclists, especially
      when they were far away. However, repeated exposure to headlight-using
      motorcyclists significantly delayed detection of an unlit motorcyclist.
      Experiment 2 showed that this delayed-detection effect occurred when only 60% of
      the motorcyclists shown were using their headlight. Under laboratory conditions,
      at least, subjects readily appear to develop a 'set' for responding on the basis
      of headlight-use, even when this is an unreliable guide to the motorcyclists'
      presence.

PMID- 7635125
TI  - Standardized task strain and system response times in human-computer interaction.
AB  - Involuntary delays in human-computer interaction, for example, system response
      times (SRTs) can increase stress. In the present study, 40 college-age subjects
      were randomly divided into an 'incentive' and a 'non-incentive' group'. Subjects
      performed a computer task with SRTs of 0.5, 1.5, and 4.5s. Physiological,
      subjective, and performance data were collected during the task. The computer
      task was designed to individually set difficulty level (i.e., mental strain),
      thus standardizing the task for all subjects. By using this procedure, changes
      resulting from SRT duration can be separated from the effects related to task
      difficulty. The results indicate that both short and long SRTs produced
      differential psychophysiological changes consistent with different types of
      stress responses. Short SRTs resulted in higher autonomic and somatic activity,
      increased positive self-reported emotional states but poorer performance. Long
      SRTs resulted in increased electrodermal activity, negative self-reported
      emotional states and better performance.

PMID- 7635126
TI  - Knee joint moments in work-related situations.
AB  - Circumstantial evidence in the literature points towards a relationship between
      heavy labour and arthrosis of the knee. The aim of this study was to demonstrate
      which occupational activities yield the greatest knee moments and thus indicate
      possible gonarthrosis-inducing occupational hazards. Twelve healthy and uninjured
      medical students were studied in set occupational situations in a laboratory for
      gait analysis, using a force plate with video display of force vectors and knee
      joints (VIFOR). With normal walking as a baseline for moment it was found that
      activities involving knee flexion, such as lifting objects from one level to the
      other, climbing stairs and ladders, and jumping down, revealed a significant
      increase in moment. On the other hand, carrying objects in one or both hands did
      not yield significant increase in knee moment compared with normal walking.
      Flexed knee lifting had significantly lower moment than jumping down from a
      height of 0.5 m on to one or both feet. Three levels of knee moment could thus be
      identified, i.e., normal walking, flexed knee lifting and jumping down.

PMID- 7635127
TI  - Effects of thermal, personal and behavioural factors on the physiological strain,
      thermal comfort and productivity of Australian shearers in hot weather.
AB  - Multiple-regression analyses were used to evaluate the separate and combined
      effects of factors that are commonly expected to influence strain and
      productivity in a hot workplace. Forty-three men were studied throughout 54 man
      days of shearing sheep and pressing wool bales, in air temperatures 19-41 degrees
      C and Wet-bulb Globe Temperature index (WBGT) 16-29 degrees C; 43% of the
      observations of WBGT exceeded 26.7 degrees C, the Threshold Limit Value (TLV) for
      the subjects' work rate of 400 W. Subjects were men of age 18-59 years, fat-free
      mass 44-77 kg, and body fat content 11-26%, who had drunk an estimated 0-207 g
      alcohol the previous evening. Afternoon mean values of rectal temperature (Tre)
      exceeded 38.0 degrees C (maximum 38.4 degrees C) in 4 of the 15 observations made
      when WBGT > TLV, and in none of those made when WBGT < TLV. Over the 10 h work
      day the subjects sweated 2.4-9.9 kg, but they replaced their sweat losses so
      successfully that warmer weather and heavier sweating were not accompanied by
      significantly greater dehydration. Surprisingly, the fatter men felt cooler, and
      those who had drunk more alcohol the previous evening had lower Tre and tended to
      be more productive. Age was not associated with any measured response. All
      factors together explained barely half the observed variation in Tre and thermal
      comfort, and almost none of the variation in productivity. The findings highlight
      the uncertainty inherent in attempts to define safe limits for occupational heat
      stress; they show how such uncertainty could restrict the usefulness in the
      shearing industry of the current heat-stress guidelines; and they demonstrate the
      effectiveness of the behavioural responses that permit shearers to perform
      sustained strenuous work in a hot environment without excessive physiological
      strain.

PMID- 7635128
TI  - Preferred viewing distances for handheld and structurally fixed displays.
AB  - This research was conducted to define viewing distance characteristics of
      individuals engaged in ordinary reading tasks. Specific attention was directed to
      assessing the potential relationship between observed distance and individual
      resting point accommodation. Consistent, statistically significant differences
      were observed across variable handheld and structurally-fixed hardcopy display
      configuration conditions. Relationships between observed viewing distance and
      resting point accommodation were not apparent. These findings suggest that simple
      eye-to-display viewing distance is fundamentally different for handheld text
      presentations and for the same text presented in a configuration similar to that
      of a video display terminal.

PMID- 7635130
TI  - Upper limb musculoskeletal disorders in highly repetitive industries: precise
      anatomical physical findings.
AB  - Physical assessment of 146 female workers in highly repetitive jobs found 54% to
      have evidence of musculoskeletal disorders in the upper limb that are potentially
      work-related. Many workers had multiple problems, and many were affected
      bilaterally (33% of workers). Muscle pain and tenderness was the largest problem,
      both in the neck/shoulder area (31%) as expected and in the forearm/hand
      musculature (23%), a previously unreported site. Most forearm muscle problems
      were found on the extensor side. Carpal tunnel syndrome was the most common form
      of neuritis with 16 people affected (7 people affected bilaterally). De
      Quervain's tenosynovitis and wrist flexor tendinitis were the most commonly found
      tendon disorders in the distal forearm (12 people affected for each diagnosis).
      The results suggest that exposure should be measured bilaterally. They also
      suggest that muscle tissue is highly vulnerable to overuse. Stressors that affect
      muscle tissue, such as static loading, should be studied in the forearm as well
      as in the shoulder.

PMID- 7635129
TI  - Effect of road layout and road environment on driving performance, drivers'
      physiology and road appreciation.
AB  - Infrastructural changes were implemented on rural 80 km/h roads in The
      Netherlands in an effort to reduce speeding. The road infrastructure changes were
      designed to produce discomfort for the speeding driver by providing noxious
      auditory and haptic feedback. On experimental roads, smooth-surface road width
      was reduced by using blocks of gravel chippings placed along the centre line and
      at intervals on road edges. It was predicted that these changes would increase
      mental load while driving, and thereby decrease speeding. In a field experiment
      28 subjects drove an instrumented vehicle over experimental and control roads. A
      decrease in driving speed and swerving behaviour was found on the experimental
      roads, and this was coupled with a decrease in heart rate variability, consistent
      with an increase in mental load. Roads in two different road-side environments
      (woodland vs. moorland) were also tested. There were differences in driver
      appraisal of the two environments, but no interactions were observed between
      these appraisals and driving performance on the experimental roads. It is
      concluded that the infrastructural measures have a useful role to play in road
      safety through a reduction in driver speeding.

PMID- 7635131
TI  - One-dimensional V-Scope analysis of habituation to simulated cross-country
      skiing.
AB  - Responses to simulated cross-country skiing were measured using the V-Scope, a
      new telemetric ultrasound motion monitor. Ten young male adults performed a total
      of 45 minutes of distributed practice on a Nordic-Track ski simulator. Over a
      period of three 15-minute sessions cadence and velocity were unchanged. Step and
      stride lengths decreased significantly (p < 0.05) after the first 15-minute
      session and then remained unchanged. There were no left-right limb differences
      across all sessions indicating a normal gait. Response variability in velocity,
      step lengths and stride length was dramatically reduced after the first exposure
      period. This study demonstrates that the V-Scope system is a useful motion
      analysing device and, on the basis of the data presented in this preliminary
      investigation, at least two 15-minute habituation sessions are required for
      initial habituation to simulated cross-country skiing.

PMID- 7635132
TI  - Mechanisms of vibration-induced interference with manual control performance.
AB  - An experiment is described in which eight subjects performed three simple tasks
      (A, B and C) in static conditions and during exposure to whole-body vertical (z
      axis) vibration at 0.5 and 4.0 Hz, at an acceleration magnitude of 2.1 ms-2
      r.m.s. All subjects performed all conditions with and without an arm support. The
      objective was to explore the mechanisms that may cause disruption of manual
      control performance during vibration exposure. With task A subjects simply held a
      control with no visual feedback of activity at the control. With task B, subjects
      used the control to hold a controlled element stationary on a display. Task C was
      the same as task B, except that subjects had improved visual feedback of movement
      of the controlled element. Results showed that both 0.5 and 4.0 Hz vibration
      caused significant increases in control activity at frequencies of up to about 1
      Hz compared with the condition without vibration. With visual feedback in task C,
      subjects were able to detect drifting of the controlled element on the display
      and introduced compensatory control activity at frequencies above about 0.2 Hz.
      The arm support reduced the magnitude of vibration transmitted to the control at
      4.0 Hz, but did not otherwise change the results.

PMID- 7635133
TI  - Effects of two kinds of clothing made from hydrophobic and hydrophilic fabrics on
      local sweating rates at an ambient temperature of 37 degrees C.
AB  - The purpose of this study was to find the effects of clothing made from
      hydrophobic and hydrophilic fabrics on the sweating physiology in environmental
      conditions where only the mechanisms of wet heat loss could occur. A comparison
      was made of the local sweat rates from the forearm and their related
      physiological parameters between polyester (E) and cotton (C) clothing at an
      ambient temperature (Ta) of 37 degrees C. Six female students, aged from 21 to 28
      years, served as subjects. The subjects wore clothing made from either fabric E
      or fabric C and rested quietly for 60 min in a chair mounted on the bed scale
      under the influences of environmental conditions of 37 degrees C and 60% relative
      humidity (rh) with an air velocity of 0.1 m.s-1. The major findings are
      summarized as follows: (1) Local sweat rates were distinctly higher in E than in
      C in five out of six female subjects. (2) Clothing surface temperatures at the
      chest level were significantly higher in C than in E. (3) The positive
      relationship between local sweat rates and mean skin temperature (Tsk) existed
      both in E and in C. However, the local sweat rates were mostly higher in E under
      the influences of the same Tsk. These results are discussed in terms of thermal
      physiology and clothing sciences. It was concluded that the different properties
      of moisture absorbency between E and C could play a role for sweating physiology
      in the environmental conditions where only the mechanism of wet heat loss could
      occur.

PMID- 7635135
TI  - Anthropometric characteristics of Japanese aged 0-59 years by analysis of a
      unified correlation matrix.
AB  - The correlation coefficient of each measured item pair for each partial group of
      similar-age, same-gender subjects is used to produce correlation coefficients for
      the entire subject group. Manipulation of the resulting equation yields a unified
      correlation matrix. Principal component analysis using this equation is applied
      to the anthropometric data of about 40,000 Japanese men and women 0-59 years old.
      As the distribution of subject age is not uniform, the number of subjects in each
      group is corrected for in the analysis, and the influence of this non-uniformity
      on the analytical results is investigated. An analysis for each individual
      partial group is also performed, and the physical features represented by the
      obtained principal factors are examined. Finally, the items crucially affecting
      each principal factor are shown to vary with age and gender.

PMID- 7635134
TI  - Cognitive failures and performance differences: validation studies of a German
      version of the cognitive failures questionnaire.
AB  - A German version of Broadbent's Cognitive Failures Questionnaire was developed
      because there was no comparable German instrument. As external validity criteria
      observable failures in everyday situations were used. The positive correlations
      were significant but moderate in size. For construct validation, inventories of
      trait anxiety, coping styles and action control were used. Most of the
      correlations were significant and in the expected direction. A maximum likelihood
      factor analysis of the questionnaire suggested that the utility of the total
      score may be doubtful. The unidimensionality of the construct requires further
      investigation.

PMID- 7635136
TI  - Psychophysical studies of repetitive wrist flexion and extension.
AB  - The purpose of this experiment was to investigate the feasibility of using
      psychophysical methods to determine maximum acceptable forces for various types
      and frequencies of repetitive wrist motion. Four adjustable work stations were
      built to simulate repetitive wrist flexion with a power grip, wrist flexion with
      a pinch grip, and wrist extension with a power grip. The study consisted of two
      separate experiments. Subjects worked for two days per week during the first
      experiment, and five days per week during the second experiment. Fifteen women
      completed the first experiment, working seven hours each day, two days per week,
      for 20 days. Repetition rates of 2, 5, 10, 15 and 20 motions per minute were used
      with each flexion and extension task. Maximum acceptable torques were determined
      for the various motions, grips, and repetition rates without dramatic changes in
      wrist strength, tactile sensitivity, or number of symptoms. Fourteen different
      women completed the second experiment, performing a wrist flexion motion (power
      grip) fifteen times per minute, seven hours per day, five days per week, for 23
      days. There were no significant differences in maximum acceptable torque from day
      to day. However, the average maximum acceptable torque for a five days per week
      exposure was 36.3% lower than for the same task performed two days per week.
      Assuming that maximum acceptable torques decrease 36.3% for other repetition
      rates and motions, tables of maximum acceptable force were developed for female
      wrist flexion (power grip), female wrist flexion (pinch grip), and female wrist
      extension (power grip).

PMID- 7635137
TI  - Physical workload of lorry drivers: a comparison of four methods of transport.
AB  - Four groups of eight lorry drivers, transporting goods on wheeled cages, as
      packed goods, on pallets, or as bulk cargo, were studied during a complete
      working day. The drivers working with bulk cargo served as a reference group.
      Manual materials handling and the working postures were studied by observation.
      The heart rate (HR) was continuously recorded and related to observed tasks. The
      relationship between HR and oxygen uptake during a simulation of loading and
      unloading and the maximal oxygen uptake (VO2max) were measured in a laboratory
      for every driver. The lorry drivers worked long hours, only the group
      transporting wheeled cages worked less than 11 h d-1 on average. Driving made up
      almost half of the total working time in all groups. In general, the highest HR
      was found during loading and unloading. Loading and unloading of wheeled cages
      was done for 2 h d-1, at 50% of VO2max. The drivers transporting packed goods and
      pallets loaded and unloaded for around 100 min d-1, at 48% and 35% of VO2max
      respectively. When the drivers of these two groups lifted, their trunks were
      flexed for more than 60% of the time. The most important difference between the
      reference group and the other groups was that the drivers of the former rarely
      pushed or pulled anything. It is suggested that the required pushing and pulling
      forces were largely responsible for the high physical workload during loading and
      unloading.

PMID- 7635138
TI  - Regulation of globin gene expression in erythroid cells.
AB  - Study of globin gene regulation has served as a useful paradigm for cell-specific
      and developmental control of transcription in higher eukaryotic cells. Recent
      work directed toward the identification and characterization of the cis
      regulatory elements and transcription factors important for both aspects of
      control is reviewed. Particular emphasis is placed on the organization and
      function of globin locus control regions, mechanisms of switching of globin gene
      expression during development, and functions of the major erythroid-specific
      nuclear regulatory proteins.

PMID- 7635140
TI  - Identification of a transcriptional regulatory factor for human aromatase
      cytochrome P450 gene expression as nuclear factor interleukin-6 (NF-IL6), a
      member of the CCAAT/enhancer-binding protein family.
AB  - Human aromatase cytochrome P450 catalyzes the ultimate reaction in the estrogen
      biosynthetic pathway by coupling with another enzyme, NADPH-cytochrome P450
      reductase, in the endoplasmic reticulum. The expression of the gene encoding the
      enzyme (CYP19) is regulated, in part, by tissue-specific promoters through the
      use of alternative-splicing mechanisms. Recently, we have localized a
      transcriptional activating element at positions -2141 to -2115 relative to the
      major cap site of the gene, by transient expression analyses in human BeWo
      choriocarcinoma cells using the bacterial chloramphenicol acetytransferase
      reporter gene ligated with CYP19 promoter sequences which regulate expression in
      this tissue. Here, we report the isolation of a cDNA encoding a DNA-binding
      protein which binds specifically to the regulatory element. The deduced amino
      acid sequence of the insert is identical to that corresponding to the DNA-binding
      domain and the dimerization domain of a transcription factor, nuclear factor
      interleukin-6 (NF-IL6), a member of the CCAAT/enhancer-binding protein (C/EBP)
      family. Studies using specific antibodies against members of the C/EBP family
      demonstrate that NF-IL6 is the major nuclear factor binding to the regulatory
      element in BeWo cells; nevertheless. C/EBP alpha also seems to be involved.
      Disruption of the NF-IL6-binding site within the regulatory element resulted in
      the disappearance of the transcriptional enhancing activity of the element,
      indicating that NF-IL6 is at least one of the nuclear factor(s) which enhances
      transcription through binding to the cis-acting element. These results indicate
      the intrinsic importance of NF-IL6 in the transcriptional regulation of CYP19
      expression.

PMID- 7635139
TI  - Overexpression of DNA methyltransferase in myoblast cells accelerates myotube
      formation.
AB  - We overexpressed mouse DNA methyltransferase in murine C2C12 myoblast cells and
      tested the isolated clones for their ability to differentiate. Significant
      numbers of the clones showed distinct myotubes 24 h after the isolated
      transformants had been induced to differentiate, whereas the parent C2C12 cells
      did not form myotubes at this time point. Transfection of the vacant vector or
      the plasmid containing the reverse-oriented DNA methyltransferase cDNA did not
      provide significant numbers of transformants with the accelerated differentiation
      phenotype, suggesting that the effect is caused by the expression of DNA
      methyltransferase. The expressions of skeletal muscle myosin and creatine kinase
      in clones that showed the accelerated differentiation-phenotype were also induced
      about 24 h earlier and at higher levels relative to the parent C2C12 or the
      control cells, indicating that the entire process of myogenesis had been
      accelerated. All the methyltransferase-transfected clones, regardless of their
      phenotypes, demonstrated about threefold higher DNA methyltransferase activity
      and higher methylation levels than those of the clones transfected with vector
      alone or the reverse-oriented plasmid. At the early stage of transfection of the
      sense-oriented plasmid, high de novo methylation activities were detected. We
      consider it likely that this high de novo methylation activity is the reason for
      the high methylation levels and the accelerated myotube formation of the clones
      transfected with the sense-oriented plasmid. In some transformants which showed
      the accelerated differentiation phenotype, MyoD1 was already fully expressed
      under the growth conditions while, in control cells, MyoD1 was expressed at low
      levels. This elevated level of MyoD1 transcription could account for the
      accelerated myotube formation observed in the transformants. The methylation
      state of the HpaII sites in exon 1 through exon 2 of the MyoD1 gene and the
      expression of the MyoD1 transcript are positively correlated.

PMID- 7635141
TI  - Purification of a processing enzyme (VmPE-1) that is involved in post
      translational processing of a plant cysteine endopeptidase (SH-EP).
AB  - A cysteine endopeptidase, designated SH-EP, occurs in the cotyledons of
      germinated seeds of Vigna mungo and acts to degrade the seed storage protein in
      protein storage vacuoles. SH-EP is synthesized on membrane-bound ribosomes as an
      inactive 45-kDa precursor, which is cotranslationally processed to a 43-kDa
      intermediate through cleavage of the signal sequence; the 43-kDa intermediate of
      SH-EP is further processed to the 33-kDa mature enzyme via 39-kDa and 36-kDa
      intermediates [Mitsuhashi, W. & Minamikawa, T. (1989) Plant Physiol. 89, 274
      279]. The present in vitro processing experiments indicated that at least two
      processing enzymes, designated VmPE-1 and VmPE-2 (V. mungo processing enzymes 1
      and 2), were involved in post-translational processing of SH-EP in cotyledons of
      V. mungo seedlings. VmPE-1 was purified from the cotyledons as a protease that
      was involved in the processing of the 43-kDa intermediate to the 36-kDa
      intermediate. The enzyme has a molecular mass of 33 kDa as estimated by
      SDS/polyacrylamide gel electrophoresis, and showed high similarity to the
      jackbean asparaginyl endopeptidase in terms of the primary structure and
      substrate specificity. We discuss the function of VmPE-1 in the processing of SH
      EP and related proteases in the cotyledons of germinated seeds.

PMID- 7635143
TI  - Chaperone-like activity of protein disulfide-isomerase in the refolding of
      rhodanese.
AB  - Protein disulfide-isomerase (PDI) in near stoichiometric concentrations promotes
      reactivation and prevents aggregation of guanidine-hydrochloride-denatured
      rhodanese during refolding upon dilution. PDI also suppresses aggregation of
      rhodanese during thermal inactivation. The above-mentioned properties displayed
      by PDI completely satisfy the definition of chaperone and provide additional
      evidence to confirm the hypothesis proposed previously [Wang, C. C. & Tsou, C. L.
      (1993) FASEB J. 7, 1515-1517] that PDI is both an enzyme and a chaperone. Since
      rhodanese contains no disulfide bonds, the chaperone-like activity of PDI acting
      on rhodanese is independent of its disulfide-isomerase activity.

PMID- 7635142
TI  - Recombinant production and biological properties of rat cytokine-induced
      neutrophil chemoattractants, GRO/CINC-2 alpha, CINC-2 beta and CINC-3.
AB  - Recently we found four cytokine-induced neutrophil chemoattractants, CINC-1, CINC
      2 alpha, CINC-2 beta and CINC-3/macrophage inflammatory protein 2 (MIP-2), in
      conditioned medium of granulation tissue obtained from carrageenin-induced
      inflammation in rats [Nakagawa, H., Komorita, N., Shibata, F., Ikesue, A.,
      Konishi, K., Fujioka, M. & Kato, H. (1994) Biochem. J. 301, 545-550]. In the
      present report, we describe recombinant production of CINC-2 alpha, CINC-2 beta
      and CINC-3 in Escherichia coli, and biological properties of these chemokines.
      Neutrophil chemotactic activities of CINC-2 alpha and 2 beta in vitro were the
      same as the activity of CINC-1. CINC-3 had an activity comparable to other CINCs,
      but showed a decrease at high concentrations. Stimulation of neutrophils with
      CINCs induced an increase in intracellular [Ca2+] dose-dependently. CINC-3 was
      more potent than the other CINCs and still induced an increase in intracellular
      [Ca2+] in rat neutrophils stimulated first with other CINCs. CINC-2 alpha, CINC-2
      beta and CINC-3 induced a comparable response to CINC-1 in the release of
      cathepsin G from rat neutrophils. Injection of CINC-2 alpha, 2 beta and 3 into
      preformed air-pouch on the back of rat induced infiltration of neutrophils to an
      extent similar to that caused by the injection of CINC-1. These data indicate
      CINC-2 alpha, 2 beta and 3 as well as CINC-1 are chemoattractants specific for
      neutrophil in vivo.

PMID- 7635144
TI  - The human UDP-N-acetylglucosamine: alpha-6-D-mannoside-beta-1,2- N
      acetylglucosaminyltransferase II gene (MGAT2). Cloning of genomic DNA,
      localization to chromosome 14q21, expression in insect cells and purification of
      the recombinant protein.
AB  - UDP-GlcNAc:alpha-6-D-mannoside [GlcNAc to Man alpha 1-6] beta-1,2-N
      acetylglucosaminyltransferase II (GlcNAc-T II, EC 2.4.1.143) is a Golgi enzyme
      catalyzing an essential step in the conversion of oligomannose to complex N
      glycans. A 1.2-kb probe from a rat liver cDNA encoding GlcNAc-T II was used to
      screen a human genomic DNA library in lambda EMBL3. Southern analysis of
      restriction endonuclease digests of positive phage clones identified two
      hybridizing fragments (3.0 and 3.5 kb) which were subcloned into pBlueScript. The
      inserts of the resulting plasmids (pHG30 and pHG36) are over-lapping clones
      containing 5.5 kb of genomic DNA. The pHG30 insert (3.0 kb) contains a 1341-bp
      open reading frame encoding a 447-amino-acid protein, 250 bp of G + C-rich 5'
      upstream sequence and 1.4 kb of 3'-downstream sequence. The pHG36 insert (3.5 kb)
      contains 2.75 kb of 5'-upstream sequence and 750 bp of the 5'-end of the open
      reading frame. The protein sequence showed the domain structure typical of all
      previously cloned glycosyltransferases, i.e. a short 9-residue putative
      cytoplasmic N-terminal domain, a 20-residue hydrophobic non-cleavable putative
      signal-anchor domain and a 418-residue C-terminal catalytic domain. Northern
      analysis of human tissues showed a major message at 3 kb and minor signals at 2
      and 4.5 kb. There is no sequence similarity to any previously cloned
      glycosyltransferases including human UDP-GlcNAc:alpha-3-D-mannoside [GlcNAc to
      Man alpha 1-3] beta-1,2-N-acetylglucosaminyltransferase I (GlcNAc-T I) which has
      445 amino acids with a 418-residue C-terminal catalytic domain. The human GlcNAc
      T I and II genes (MGAT1 and MGAT2) map to chromosome bands 5q35 and 14q21,
      respectively, by fluorescence in situ hybridization. The entire coding regions of
      human GlcNAc-T I and II are each on a single exon. There is 92% identity between
      the amino acid sequences of the catalytic domains of human and rat GlcNAc-T II.
      Southern analysis of restriction enzyme digests of human genomic DNA indicates
      that there is only a single copy of the MGAT2 gene. The full-length coding region
      of GlcNAc-T II has been expressed in the baculovirus/Sf9 insect cell system, the
      recombinant enzyme has been purified to near homogeneity with a specific activity
      of about 20 mumol.min-1.mg-1 and the product synthesized by the recombinant
      enzyme has been identified by high-resolution 1H-NMR spectroscopy and mass
      spectrometry.

PMID- 7635145
TI  - Effects of the anticonvulsant, valproate, on the expression of components of the
      cytochrome-P-450-mediated monooxygenase system and glutathione S-transferases.
AB  - It has been shown previously that the anticonvulsant agent, sodium valproate,
      induces certain cytochrome P-450 monooxygenase activities and decreases
      glutathione S-transferase activity. We have used Western blotting, RNase
      protection assays and Northern blot hybridization to determine the effects of
      valproate on the abundance of individual components of the cytochrome P-450
      monooxygenase and of glutathione S-transferase subunits. Due to the short half
      life of the drug in rats we have used an in vitro experimental system comprised
      of rat hepatocytes co-cultured with rat primitive biliary epithelial cells.
      Valproate was shown to be a potent inducer of two members of the cytochrome P-450
      (CYP)2B subfamily, CYP2B1 and 2B2. The induction of the proteins was mediated at
      the level of the mRNAs, with the mRNA for CYP2B1 being more highly induced than
      that for CYP2B2. The drug also induced, but to a much lesser extent, two
      important components of the cytochrome-P-450-mediated monooxygenase system, NADPH
      dependent cytochrome P-450 reductase and cytochrome b5, and their corresponding
      mRNAs. Thus, the effects of valproate on cytochromes P-450 and other components
      of the cytochrome-P450-mediated monooxygenase system mimic those of another,
      structurally diverse, antiepileptic drug, phenobarbital. However, in contrast to
      phenobarbital, which induces glutathione S-transferase subunits 1, 2, 3, 4 and 7,
      valproate selectively decreases the abundance of subunits 3 and/or 4. It has been
      shown previously that CYP2B1 is involved in the production of metabolites of
      valproate implicated in hepatotoxicity. The induction of this protein by
      valproate would thus contribute substantially to the hepatotoxic effects
      associated with the drug.

PMID- 7635146
TI  - Cloning and expression of glucosidase I from human hippocampus.
AB  - Glucosidase I, the first enzyme in the N-linked oligosaccharide processing
      pathway, cleaves the distal alpha 1,2-linked glucose residue from the Glc3-Man9
      GlcNAc2 oligosaccharide precursor highly specifically. A human hippocampus cDNA
      library was screened against oligonucleotide probes, generated by PCR using
      primers derived from the amino acid sequences of tryptic peptides of pig liver
      glucosidase I. Two independent lambda clones were isolated which allowed the
      construction of a full-length glucosidase I cDNA of 2881 bp. This cDNA construct
      encodes, in a single open reading frame, a polypeptide of 834 amino acids
      corresponding to a molecular mass of 92 kDa. The 92-kDa protein contains a single
      N-glycosylation site of the Asn-Xaa-Thr/Ser type at Asn655, as well as a strongly
      hydrophobic sequence close to its N-terminus (amino acids 38-58) which, most
      likely, functions as a transmembrane anchor. The amino acid sequences of all
      tryptic peptides of the pig liver enzyme were found, with little deviation,
      within the coding sequence. This demonstrates the authenticity of the cDNA
      construct and the close evolutionary relationship between the enzymes from human
      hippocampus and pig liver. In contrast, the nucleotide and amino acid sequence
      revealed no homology with other processing enzymes cloned so far. Transfection of
      COS 1 cells with the glucosidase I cDNA construct resulted in overexpression
      (about fourfold) of enzymic activity, which was inhibited strongly by 1
      deoxynojirimycin or N,N-dimethyl-deoxynojirimycin. The expressed enzyme, with a
      molecular mass of 95 kDa, is degraded by endoglycosidase H to a 93-kDa form,
      indicating that it carries a high-mannose oligosaccharide chain at Asn655. The
      presence of this glycan is in line with the localization of glucosidase I in the
      lumen of the endoplasmic reticulum, shown by immunofluorescence microscopy. The
      hydrophobicity profile as well as the removal by trypsin of an approximately 4
      kDa polypeptide from the membrane-associated glucosidase I in intact microsomal
      structures, supports the view that the enzyme is a type-II transmembrane
      glycoprotein, which contains a short cytosolic tail of approximately 37 amino
      acids, followed by a single transmembrane domain and a large C-terminal catalytic
      domain located on the luminal side of the endoplasmic reticulum membrane.

PMID- 7635147
TI  - 1H-NMR study of a cobalt-substituted blue copper protein: Pseudomonas aeruginosa
      Co(II)-azurin.
AB  - Substitution of copper by cobalt in blue copper proteins gives a paramagnetic
      metalloderivative suitable for paramagnetic NMR studies. A thorough analysis of
      the 1H-NMR spectrum of Pseudomonas aeruginosa Co(II)-azurin is presented here.
      All the observable contact-shifted signals as well as many other paramagnetic
      signals from protons placed up to about 1.0 nm around the metal center, including
      some residues belonging to functionally important parts of the protein like the
      hydrophobic patch and the His35 region, have been assigned. The results obtained
      permit the detection and study of structural variations like those originated by
      the His35 ionization, and allow us to draw a feasible picture of the metal
      coordination site. Contact-shifted signals correspond to the same five residues
      which are found in the coordination sphere of the native Cu(II)-azurin, i.e.
      His46, His117, Cys112, Met121 and Gly45. Among them, the histidine residues
      present a pattern of resonances typical for histidines coordinated to cobalt in
      other cobalt protein derivatives, and the cysteine signals clearly indicate a
      strong interaction with the paramagnetic Co(II) ion. In contrast, the Met121
      signals indicate a weak but still existent contact interaction with the metal
      center. On the other hand, the very weak copper ligand, Gly45, appears here as
      clearly coordinated to cobalt. Results are consistent with a distorted
      tetrahedral metal site with the cobalt deviated from the N2S plane towards the
      Gly45 O axial position and weakly interacting with the Met121 sulfur.

PMID- 7635148
TI  - The basic subdomain of the c-Jun oncoprotein. A joint CD, Fourier-transform
      infrared and NMR study.
AB  - The structural properties of the basic subdomain of the basic zipper (bZIP)
      protein c-Jun were examined by joint means of 1H-NMR, CD and Fourier-transform
      infrared (FTIR) spectroscopies. The basic subdomain (residues 252-281 in c-Jun)
      is responsible for sequence-specific recognition of DNA. A modified basic
      subdomain bSD (residues 1-35) and its N-terminal part and C-terminal part
      fragments (NP, residues 1-19; and, CP, residues 16-35) were prepared by solid
      phase synthesis and purified by HPLC. In aqueous solution, in the absence of DNA,
      bSD behaved mostly as an unstructured peptide characterized by only 5% alpha
      helix. However, upon mixing bSD and a specific DNA fragment, i.e. a CRE(cAMP
      responsive element)-containing hexadecanucleotide, the alpha helix was stabilized
      to an extent of 20% at 20 degrees C or 35% at 2 degrees C. At the same time, no
      significant change could be detected in the DNA spectra. Addition of
      trifluoroethanol to an aqueous bSD sample resulted in an increase of the alpha
      helix content so that about 60% of alpha helix was found at a ratio of 75%
      trifluoroethanol (20 degrees C). These effects were reflected in both CD and FTIR
      measurements. Changes shown by the CD spectra during the process suggested a
      mechanism dominated by a two-state helix/unordered transition. NMR data, namely
      alpha H chemical shifts, NOE cross-peaks and NH temperature coefficients provided
      indications for extended or nascent helix structures within four short stretches
      dispersed along the sequence for c-Jun bSD, contrasting with the unique and
      continuous stretch reported for Gcn4 (yeast general control protein 4) bSD in
      aqueous solution. Trifluoroethanol stabilized the alpha-helix structure mainly at
      these four sites. The malleability of the basic subdomain of c-Jun was emphasized
      in relation to its ability to fit the DNA helix in adopting an alpha-helix
      structure. The complex formation apparently requires substantial conformational
      change from the peptide and only little from the oligonucleotide.

PMID- 7635149
TI  - The folding and assembly pathway of tumour necrosis factor TNF alpha, a globular
      trimeric protein.
AB  - The mechanisms of folding and assembly of the globular, trimeric protein tumour
      necrosis factor-alpha (TNF) were studied by chemical cross-linking. This revealed
      the rapid accumulation of a dimeric intermediate. Under the conditions of
      renaturation used, formation of the trimer is complete within six minutes. The
      kinetics of change of intrinsic and 8-anilino-1-naphthalene sulfonic acid
      fluorescence are first order and, combined with the kinetics of association,
      reveal the presence of folding steps both before and subsequent to formation of
      the trimer. Results from gel exclusion chromatography and kinetics, together with
      the existence of an acid-induced molten globule, support the conclusion that TNF
      folds and assembles through a trimeric molten globule.

PMID- 7635150
TI  - Kinetics of streptolysin O self-assembly.
AB  - Streptolysin O is a member of a family of membrane-damaging toxins that bind to
      cell membranes containing cholesterol and then polymerize to form large pores. We
      have examined the kinetics of toxin action using 125I-labelled streptolysin O.
      Binding of toxin monomers to membranes displays first-order kinetics and is
      reversible; the rate of desorption from red cells shows a marked dependence on
      temperature. To study oligomerization, toxin was bound to erythrocytes at 0
      degrees C. Oligomer formation was then triggered by a sudden temperature shift
      and stopped by solubilization of membranes with deoxycholate. While at moderately
      high streptolysin O concentrations oligomerization behaves as a reaction of
      second order, the kinetic pattern changes with increasing toxin concentration. We
      show that this can be accounted for by the assumption of a two-step reaction
      mechanism: two membrane-bound monomers first associate into a start complex,
      which then is rapidly extended by the sequential addition of further monomers up
      to the final oligomer size.

PMID- 7635151
TI  - Characterization of a 2[4Fe-4S] ferredoxin obtained by chemical insertion of the
      Fe-S clusters into the apoferredoxin II from Rhodobacter capsulatus.
AB  - The Rhodobacter capsulatus ferredoxin II (FdII) belongs to a family of 7Fe
      ferredoxins containing one [3Fe-4S] cluster and one [4Fe-4S] cluster. This
      protein, encoded by the fdxA gene, has been overproduced in Escherichia coli as a
      soluble apoferredoxin. The purified recombinant protein was subjected to
      reconstitution experiments by chemical incorporation of the Fe-S clusters under
      anaerobic conditions. A brown protein was obtained, the formation of which was
      dependent upon the complete unfolding of the polypeptide prior to incorporation
      of iron and sulfur atoms. The yield of the reconstituted product was higher when
      the reaction was carried out at slightly basic pH. The reconstituted ferredoxin
      was purified and shown to be distinct from the native [7Fe-8S] ferredoxin, based
      on several biochemical and spectroscopic criteria. In the oxidized state, EPR
      revealed the quasi-absence of [3Fe-4S] cluster. 1H-NMR spectroscopic analyses
      provided evidence that the protein was reconstituted as a 2[4Fe-4S] ferredoxin.
      This conclusion was further supported by the determination by electrospray mass
      spectrometry of the molecular mass of the reconstituted protein, which matched
      within 2 Da to the mass of the FdII polypeptide incremented of eight atoms each
      of iron and sulfur. Exposure of the reconstituted protein to air resulted in a
      fast and irreversible oxidative denaturation of the Fe-S clusters, without
      formation of [7Fe-8S] form. Unlike the natural 7Fe ferredoxin, the reconstituted
      ferredoxin appeared incompetent in an electron-transfer assay coupled to
      nitrogenase activity. The fact that the apoFdII was reconstituted as a highly
      unstable 8Fe ferredoxin instead of the 7Fe naturally occurring FdII is discussed
      in relation to the results obtained with other types of ferredoxins.

PMID- 7635152
TI  - Stability, activity and structure of adenylate kinase mutants.
AB  - Sequence/structure relationships have been explored by site-directed mutagenesis
      using a structurally known adenylate kinase. In particular the effects of helix
      capping and nonpolar core expansion on thermodynamic stability have been
      analyzed. Six point mutations were produced and characterized by SDS/PAGE, native
      PAGE, isoelectric focussing, electrophoretic titration, enzyme kinetics, and X
      ray structure analysis. Heat-denaturation experiments yielded melting
      temperatures Tm and melting enthalpy changes delta Hm. The heat capacity change
      delta Cp of the wild-type enzyme was determined by guanidine hydrochloride
      denaturation in conjunction with Tm and delta Hm. Using the wild-type delta Cp
      value, Gibbs free energy changes delta G at room temperature were calculated for
      all mutants. Four mutants were designed for helix capping stabilization, but only
      one of them showed such an effect. Because of electrostatic interference with the
      induced-fit motion, one mutant decreased the catalytic activity strongly. Two
      mutants expanded nonpolar cores causing destabilization. The mutant with the
      lower stability could be crystallized and subjected to an X-ray analysis at 223
      pm resolution which showed the structural changes. The enzyme was stabilized by
      adding a -Pro-His-His tail to the C-terminal alpha-helix for nickel-chelate
      chromatography. This addition constitutes a helix cap. Taken together, the
      results demonstrate that stabilization by helix capping is difficult to achieve
      because the small positive effect is drowned by adverse mutational disruption.
      Further addition of atoms to nonpolar cores destabilized the protein, although
      the involved geometry changes were very small, demonstrating the importance of
      efficient packing.

PMID- 7635153
TI  - Human pterin-4 alpha-carbinolamine dehydratase/dimerization cofactor of
      hepatocyte nuclear factor-1 alpha. Characterization and kinetic analysis of wild
      type and mutant enzymes.
AB  - Pterin-4a-carbinolamine dehydratase/dimerization cofactor for hepatocyte nuclear
      factor-1 alpha is a protein with two different functions. We have overexpressed
      and purified the human wild-type protein, and its Cys81Ser and Cys81Arg mutants.
      The Cys81Arg mutant has been proposed to be causative in a hyperphenylalaninaemic
      patient [Citron, B. A., Kaufman, S., Milstien, S., Naylor, E. W., Greene, C. L. &
      Davis, M. D. (1993) Am. J. Hum. Genet. 53, 768-774]. The dehydratase behaves as a
      tetramer on gel filtration, while cross-linking experiments showed mono-, di-,
      tri-, and tetrameric forms, irrespective of the presence of the single Cys81.
      Sulfhydryl-modifying reagents did not affect the activity, but rather showed that
      Cys81 is exposed. Various pterins bind and quench the tryptophan fluorescence
      suggesting the presence of a specific binding site. The fluorescence is destroyed
      upon light irradiation. Wild-type and the Cys81Ser protein enhance the rate of
      the phenylalanine hydroxylase assay approximately 10-fold, a value similar to
      that of native dehydratase from rat liver; the Cys81Arg mutant, in contrast, has
      significantly lower activity. This is compatible with the hypothesis that the
      dehydratase is a rate-limiting factor for the in vivo phenylalanine hydroxylase
      reaction. The three proteins enhance the spontaneous dehydration of the synthetic
      substrate 6,6-dimethyl-7,8-dihydropterin-4a-carbinolamine approximately 50-70
      fold at 4 degrees C and pH 8.5. The results are discussed in view of the recently
      solved three-dimensional structure of the enzyme [Ficner, R., Sauer, U. W.,
      Stier, G. & Suck, D. (1995) EMBO J. 14, 2032-2042].

PMID- 7635154
TI  - Structure of six 3-deoxy-D-glycero-D-galacto-nonulosonic acid(Kdn)-containing
      oligosaccharide-alditols released from oviduct secretions of Ambystoma maculatum.
      Characterization of the sequence fucosyl(alpha 1-2)[fucosyl(alpha 1
      3)]fucosyl(alpha 1-4)-3-deoxy-D-glycero-D-galacto-nonulosonic acid.
AB  - The O-linked acidic oligosaccharides of the jelly coat surrounding the eggs of
      Ambystoma maculatum were analyzed by NMR spectroscopy. The structures of the
      major oligosaccharides were established as follows where Kdn represents 3-deoxy-D
      glycero-D-galacto-nonulsonic acid and GalNAc-ol is N-acetylgalactosaminitol:
      [sequence: see text] As shown for five other amphibian species, the structures of
      these carbohydrate chains appear to be species specific and can afford a basis
      for molecular taxonomy. These new sequences also reflect the occurrence of
      specific fucosyltransferase activities that are characteristic of Ambystoma
      maculatum.

PMID- 7635155
TI  - Structure of four acidic oligosaccharides from the jelly coat surrounding the
      eggs of Xenopus laevis.
AB  - Novel acidic oligosaccharides were released by reductive beta-elimination from
      the jelly coat eggs of the Anuran Xenopus laevis. According to the structural
      analysis of these oligosaccharide-alditols, the following structures are
      proposed: [sequence: see text] where Kdn, 3-deoxy-D-glycero-D-galactononulosonic
      acid. These results confirm the species specificity of the glycanic structures
      present in the secretion of amphibian oviducts, and may form the basis of a
      specific egg-sperm recognition process.

PMID- 7635156
TI  - Mannosylated lipoarabinomannan interacts with phagocytes.
AB  - Infection by Mycobacterium tuberculosis first involves its adhesion to
      mononuclear host phagocytes. Various macrophage opsonic and non-opsonic receptors
      are known to mediate this adhesion, with some specificity of mannosyl receptors
      for the more virulent strains. Mannosylated lipoarabinomannan, a major component
      of cell walls from M. tuberculosis and Mycobacterium bovis BCG, is endowed with
      mannooligosaccharide units that could mediate its binding to these latter
      receptors. To explore its interaction with murine immune cells by flow cytometry,
      we report a new procedure to fluorescently tag the polysaccharide molecules. We
      covalently labeled mannosylated lipoarabinomannan from M. bovis BCG with biotin,
      allowing formation of stable complexes with streptavidin coupled to a
      fluorochrome. In this work, we demonstrated that this major carbohydrate antigen
      interacts selectively with murine phagocytes, i.e. granulocytes and macrophages.
      This binding was affected by temperature and was serum- and divalent-cation
      dependent. It also appears to involve a metabolically recycling protein receptor
      on the phagocyte surface and mannosyl aggretopes on the mannosylated
      lipoarabinomannan molecule. Thus, the latter may provide a means for mycobacteria
      to bind to and invade their host phagocytes. This molecule could constitute one
      of the early factors of mycobacterial virulence.

PMID- 7635157
TI  - Photoinactivation of photosystem II induces changes in the photochemical reaction
      center II abolishing the regulatory role of the QB site in the D1 protein
      degradation.
AB  - The effect of 3-(3,4-dichlorophenyl)-1,1-dimethyl urea (diuron) binding at the
      secondary quinone (QB) binding site of reaction center II (RCII), on the high
      light-induced degradation of the RCII proteins D1 and D2, and the core proteins
      CP43 and CP47 was investigated in vivo in Chlamydomonas reinhardtii. The
      degradation of the RCII-D2 and the CP43 proteins shows a short lag relative to
      that of the RCII-D1 protein. Diuron retards but does not prevent the degradation
      of RCII-D1, D2 and CP43 proteins. The degradation of the CP47 protein is not
      retarded by diuron. The RCII-D1 protein present in cells photoinactivated in the
      presence of diuron is subsequently degraded in cells transferred to low light or
      to darkness. The protein can be replaced (turnover) at least partially under both
      conditions. The RCII-D1 protein is not degraded during photoinactivation of a
      cytochrome-bf-defective mutant. Degradation occurs however when the cells are
      returned to low light permitting slow reoxidation of plastoquinol [Zer, H.,
      Prasil, O. & Ohad, I. (1994) J. Biol. Chem. 269, 17,670-17,676]. Addition of
      diuron does not prevent the degradation of the protein at this stage. Tryptic
      digestion of the RCII-D1 protein is partially inhibited by diuron in isolated
      thylakoids [Trebst, A., Depka, B., Kraft, B. & Johanningmeier, U. (1988)
      Photosynth. Res. 18, 163-177] but not in thylakoids obtained from
      photoinactivated cells. We conclude that photoinactivation induces a series of
      sequential changes in RCII exposing the cleavage site of the RCII-D1 protein to
      degradation and abolishing the regulatory role of the QB site occupancy by
      plastoquinone or analog ligands on the cleavage process. The degradation of the
      RCII-D2 and CP43 proteins may be a secondary process following modification
      and/or loss of the RCII-D1 protein.

PMID- 7635158
TI  - Transient acquired thermotolerance in Drosophila, correlated with rapid
      degradation of Hsp70 during recovery.
AB  - Acquired thermotolerance, measured either as increased cell viability following a
      lethal heat shock or by translational thermotolerance, appears rapidly following
      a 'priming' heat treatment, but also decays rapidly. 4 hours after priming
      heating thermotolerance is reduced by > 50% and by 9 hours it is virtually
      undetectable. Heat-shock protein 70 (Hsp70) turns over with a half-life of
      approximately 2 hours, and the decline in its intracellular abundance parallels
      the loss of acquired thermotolerance. Continuous heat shock extends the half-life
      of Hsp70 to approximately 7 hours. When Hsp70 is expressed at normal temperature
      using a metallothionein promoter, only partial acquired translational
      thermotolerance results. The results suggest that acquired thermotolerance is
      tightly regulated in Drosophila and partly, but not wholly, determined by post
      translational regulation of Hsp70 levels.

PMID- 7635159
TI  - Pattern formation on cardiac troponin I by consecutive phosphorylation and
      dephosphorylation.
AB  - Two serine residues located adjacently in the heart-specific N-terminus of
      cardiac troponin I can be phosphorylated in vivo. Both residues are sequentially
      phosphorylated and dephosphorylated by cAMP-dependent protein kinase (PKA) and
      protein phosphatase 2A (PP2A). The concentration changes of the different
      troponin I species have been determined separately for the phosphorylation and
      dephosphorylation reaction and approximated by time courses predicted by a
      reaction model. Dependent on the concentration ratio of active protein
      kinase/protein phosphatase, four different troponin I species can be generated;
      one nonphosphorylated, two monophosphorylated and one bisphosphorylated. This
      pattern generation will be observed in proteins phosphorylated and
      dephosphorylated by a single protein kinase and phosphatase on more than one site
      and is a new principle inherent in signal cascades.

PMID- 7635160
TI  - Human topoisomerase II alpha is phosphorylated in a cell-cycle phase-dependent
      manner by a proline-directed kinase.
AB  - Topoisomerase II is essential for chromosome condensation and segregation at
      mitosis in eukaryotic cells, but the mechanism of its regulation is not clearly
      understood. We have investigated whether or not the alpha isozyme of human
      topoisomerase II is phosphorylated in a cell-cycle phase-dependent manner. Two
      dimensional tryptic phosphopeptide mapping revealed that several sites on HeLa
      topoisomerase II alpha protein were phosphorylated predominantly or exclusively
      during the G2 and M phases. To identify the protein kinases involved in this cell
      cycle phase-specific phosphorylation, oligohistidine-tagged recombinant domains
      of the topoisomerase II alpha protein were expressed in Escherichia coli,
      purified by affinity chromatography and phosphorylated in vitro by different
      protein kinases. Phosphorylation of the C-terminal domain of the topoisomerase II
      alpha protein by the universal mitotic controller, p34cdc2, generated multiple
      tryptic phosphopeptides, many of which corresponded to the G2/M-phase-specific
      phosphorylation sites observed in vivo. The same phosphopeptides were obtained
      following phosphorylation of the C-terminal domain in vitro by the mitogen
      activated protein kinase. Site-directed mutagenesis studies identified five of
      these sites of phosphorylation, each of which comprised a serine-proline motif.
      Our data implicate one or more proline-directed kinases in the cell-cycle
      dependent regulation of topoisomerase II alpha enzyme activity in human cells.

PMID- 7635162
TI  - Regulatory proteolysis of the major light-harvesting chlorophyll a/b protein of
      photosystem II by a light-induced membrane-associated enzymic system.
AB  - An endogenous proteolytic activity associated with spinach chloroplast thylakoid
      membranes has been identified. This enzymic activity is involved in the
      degradation of the major light-harvesting chlorophyll a/b protein of photosystem
      II (LHCII) in response to exposure of leaves to increased irradiance. This
      proteolysis of LHCII requires an induction period and can only be detected 48-72
      hours after transfer of the plants from low-intensity to high-intensity light.
      Once initiated by high-intensity light, the degradation of LHCII can readily
      occur in complete darkness. The proteolysis can, after induction in vivo, be
      experimentally followed in vitro, both in isolated intact chloroplasts and
      thylakoid membranes. The proteolytic process is strictly dependent on ATP and the
      protease involved is of the serine or cysteine type. The activity can be released
      from isolated thylakoid membranes by washing with high concentrations of NaCl and
      reconstituted by readdition of the desalted wash supernatant. It is concluded
      that the protease is extrinsically bound to the outer surface of the stroma
      exposed regions of the stacked thylakoid membrane. The mechanism for the
      induction of the proteolytic process as well as its relation to previously
      described thylakoid proteases will be discussed.

PMID- 7635161
TI  - Octanoate affects 2,4-dinitrophenol uncoupling in intact isolated rat
      hepatocytes.
AB  - When intact isolated rat hepatocytes, either incubated or perifused, were
      uncoupled by 2,4-dinitrophenol, we found that the effect on glucose and
      lactate+pyruvate fluxes, cytosolic and mitochondrial redox states and ATP/ADP
      ratios were dependent on the nature of the exogenous substrate added. 2,4
      Dinitrophenol addition (0.25 mmol/l) to cells perifused with dihydroxyacetone (10
      mmol/l) resulted in a modest and transient activation of oxygen uptake
      accompanied by a surprising rise in lactate/pyruvate ratio indicating an increase
      in the cytosolic NADH/NAD+ ratio. In addition, such uncoupling, fully abolished
      glucose production, enhanced lactate+pyruvate flux, and strongly decreased
      cytosolic and mitochondrial ATP/ADP ratios. In these steady-state conditions,
      further addition of octanoate (0.4 mmol/l) induced a large and sustained
      enhancement of respiration with a concomitant decrease in the lactate/pyruvate
      ratio, whereas glucose flux was restored to some extent and cytosolic and
      mitochondrial ATP/ADP ratios increased. Inhibition of the malate-aspartate
      shuttle by the transaminase inhibitor aminooxyacetate (0.3 mmol/l) did not modify
      the effect of 2,4-dinitrophenol with dihydroxyacetone alone whereas it decreased
      the maximal stimulation of oxygen uptake after octanoate addition. In view of
      these results we propose the following conclusions. The uncoupling of intact
      cells by 2,4-dinitrophenol inhibits the translocation of reducing equivalents
      into the mitochondrial matrix probably by impairing the malate-aspartate shuttle.
      This explains the increase in the cytosolic NADH/NAD+ ratio and the transient
      activation of respiration with dihydroxyacetone. Fatty acid addition to cells
      uncoupled with 2,4-dinitrophenol appears to restore a mitochondrial membrane
      potential, probably by providing the respiratory chain with reduced cofactors
      directly in the matrix, thus allowing the transfer of reducing equivalents across
      the mitochondrial membrane. The restoration, to some extent, of a protonmotive
      force to uncoupled cells by fatty acid addition is also supported by an increase
      in ATP synthesis as evidenced by a glucose synthesis with dihydroxyacetone as
      gluconeogenic substrate.

PMID- 7635163
TI  - Surface mapping of the ligand-filled C-terminal half of the porcine estradiol
      receptor by restricted proteolysis.
AB  - The ligand-filled 32-kDa fragment of the porcine estradiol receptor extending
      from His267 to the C-terminal Ile595 was purified to homogeneity by adsorption to
      mAb 13H2. The native protein was exposed at 4 degrees C to a panel of proteases:
      thermolysin, subtilisin, pronase, elastase, ficin, bromelain, endopeptidase Lys
      C, both in the dimer and the monomer state, and chymotrypsin at pH 8.2 only. The
      digests were analysed by SDS/PAGE/Western blotting for Coomassie staining and
      immunostaining. Peptides were sequenced from blots. The majority of cleavage
      sites in upper domain E (8 out of 11) amassed in the Leu296-Leu310 stretch.
      Cleavage at Leu319 was seen with subtilisin and at Tyr328 with chymotrypsin.
      Susceptability to enzymic proteolysis was also pronounced in Thr465-Glu470 at the
      center of domain E. Three peptides, 13 kDa with thermolysin, beginning at Leu337,
      6 kDa and, in low yield, 5 kDa with endopeptidase Lys-C beginning at Asp473 resp.
      Cys417 were only obtained from the monomer substrate. The various digests
      featured either 27-23-kDa peptides or mixtures of 17-13-kDa and 12-7-kDa peptides
      separable by SDS/PAGE. All peptides with N-termini between Leu297 and Ser329
      reacted with mAb 13H2. The digests showed high peaks of bound estradiol in the
      dimer position of 32-kDa fragment controls on density gradient centrifugation at
      pH 7.4. However, the property of proton-driven dissociation was only preserved in
      the pronase, elastase and chymotrypsin digests with peptides extending beyond the
      His547-ArgLeuHis550 motif. The preservation of the estradiol-binding niche in the
      tightly complexed peptides of domain E was also demonstrated by refilling after
      steroid removal. The sites exposed to proteolytic enzymes and the epitope for
      13H2 attachment are in good agreement with surface probability plots.

PMID- 7635164
TI  - The effect of testosterone and DOI (1-(2,5-dimethoxy-4-iodophenyl)-2
      aminopropane) on male sexual behavior of rats.
AB  - The effects of a 5-HT2 receptor agonist, DOI (1-(2,5-dimethoxy-4-iodophenyl)-2
      aminopropane; 0.5 mg/kg), on the behavior of male rats at different ages when
      given alone or with different levels of testosterone, in the presence of sexually
      receptive and non-receptive females are presented. DOI increased mounting and/or
      mount plus thrusting behavior in adult males with receptive females. In pre
      pubertal males, DOI increased the frequency of pursuit and genital sniffing in
      the presence of receptive females, but not of non-receptive ones, when no mounts
      or thrustings were recorded. In castrated rats treated with testosterone and
      tested with receptive females, DOI increased the frequency of thrusting behavior,
      but in castrated rats without testosterone treatment, DOI produced no change. DOI
      did not induce mounting in pre-pubertal or castrated rats without testosterone
      substitution therapy. These results suggest that DOI influences male sexual
      behavior through a neural system that is modulated by testosterone.

PMID- 7635165
TI  - Sexual dimorphic effects of chronic phencyclidine in rats.
AB  - The behavioral effects of phencyclidine (PCP) were studied in male and female
      Sprague-Dawley rats to determine if chronic infusions would result in sexually
      dimorphic effects. Rats were trained to make operant responses for food during 30
      min response periods that occurred 4 times each day. After attaining stable
      baseline behaviors, 10 mg of PCP/kg/day was infused s.c. for 10 days. Females
      were more profoundly affected than males. In the females, response rates were
      suppressed to 30-71% of control rates during the first 7 days of infusion. In
      contrast, response rate in male rats never fell below 77% of control during the
      infusion period. By the eighth infusion day both sexes had become tolerant to
      these behavioral effects. After stopping infusions there was clear evidence that
      behavioral dependence had developed; however, the abstinence effects in males and
      females were similar. Saturation studies of [3H]dizocilpine (MK-801; (+)-5-methyl
      10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine) binding to brain membranes
      were conducted to determine if there were sex-dependent receptor differences.
      There were no significant differences in Kd +/- S.D. (7.6 +/- 1.5 and 7.1 +/- 0.9
      nM for males and females, respectively) or Bmax +/- S.D. (4.1 +/- 0.2 and 4.0 +/-
      0.5 pmol/mg protein for males and females, respectively).

PMID- 7635166
TI  - The alpha 2-adrenoceptor antagonist, (+)-efaroxan, enhances acetylcholine release
      in the rat cortex in vivo.
AB  - Noradrenergic modulation of the cortical cholinergic system in vivo was studied
      by examining the effect of the selective alpha 2-adrenoceptor antagonist (+)
      efaroxan on cortical acetylcholine outflow in the conscious rat, using the
      microdialysis technique. (+)-Efaroxan produced a dose-dependent increase in
      acetylcholine outflow (up to 300% at 0.63 mg/kg) which persisted for up to 3 h
      and which was stereospecific. The results demonstrate that rat cortical
      acetylcholine release can be augmented by (+)-efaroxan and that alpha 2
      adrenoceptors may be involved. (+)-Efaroxan may have therapeutic potential in
      disorders in which cortical acetylcholine release is deficient.

PMID- 7635167
TI  - Metabotropic glutamate receptor agonists inhibit endogenous glutamate release
      from rat striatal synaptosomes.
AB  - A striatal synaptosomal preparation was used to assess the action of metabotropic
      glutamate receptor (mGlu receptor) agonists on 4-aminopyridine (2 mM)-stimulated
      endogenous glutamate release. 4-Aminopyridine alone increased basal glutamate
      release by 6.89 +/- 0.74 nmol/mg. The mGlu receptor agonists L-2-amino-4
      phosphonobutyric acid (L-AP4) (IC50 approximately 0.2 microM) and (1S,3S)-1-amino
      cyclopentane-1,3-dicarboxylic acid (IC50 approximately 0.2 microM) inhibited 4
      aminopyridine-stimulated release. The putative mGlu receptor antagonist (S)-alpha
      methyl-L-AP4, which itself inhibited 4-aminopyridine-stimulated release (IC50
      approximately 10 microM), did not inhibit the effects of the two agonists.

PMID- 7635168
TI  - Alkylating derivative of hexadecamethonium protects muscle synaptic
      acetylcholinesterase against inhibition.
AB  - The action of the alkylating derivative of hexadecamethonium on frog
      neuromuscular transmission was studied with the help of intracellular
      microelectrodes. Treatment of frog m. cutaneous pectoris-n. pectoralis
      preparations with the alkylating derivative of hexadecamethonium (0.5 microM) for
      30 min led to an irreversible decrease in the amplitude of the end-plate
      potentials by 2.5-fold without a change of their latency period or quantal
      content. Such treatment led also to a considerable reduction of the
      anticholinesterase effects of neostigmine and of the organophosphorus
      irreversible inhibitor, armine. Thus, when applied to intact nerve-muscle
      preparations, neostigmine (2 microM) or armine (1 microM) increased the amplitude
      of end-plate potentials by 80-90%, and the rise time and half-decay time by about
      2- to 3-fold. However, after the nerve-muscle preparations were pretreated with
      the alkylating derivative of hexadecamethonium (0.5 microM, for 30 min), the
      amplitude of end-plate potentials increased by 20-25%, rise time by 15-20% and
      half-decay time by 40-50% only. Investigation of muscle acetylcholinesterase
      activity, using the Ellman technique, showed that the alkylating derivative of
      hexadecamethonium diminished the sensitivity of the muscle acetylcholinesterase
      to inhibition without exerting its own inhibitory action.

PMID- 7635169
TI  - Peripheral opioid modulation of pain and inflammation in the formalin test.
AB  - The effects of local treatment with opioid receptor agonists on the early (0-10
      min) and late (20-40 min) behavioural response and extravasation induced by
      intraplantar injection of 1% formalin in rats were examined. The mu-opioid
      receptor agonist [D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin (DAMGO) depressed pain
      behaviour in the late phase, and extravasation in both phases. The kappa-opioid
      receptor agonist trans-(+/-)-3,4-dichloro-N-methyl-N-(2-[1-pyrrolidinyl]
      benzeneacetamide methanesulfonate (U50,488H) suppressed the behavioural response
      in both phases, but extravasation was enhanced in the early phase and not altered
      in the late phase. The delta-opioid receptor agonist [D-Pen2,5]enkephalin (DPDPE)
      enhanced the behavioural response in the late phase, but inhibited extravasation
      in the both early and late phases. Systemic injection of the agonists had no
      effects, and pretreatment with s.c. naloxone methiodide reversed the effects of
      locally administered agonists. These data (1) support the notion that different
      pathophysiological mechanisms underlie the two phases of the formalin test, and
      (2) indicate that depending on the receptor specificity, opioid receptor agonists
      have both pro- and antinociceptive effects, as well as pro- and antiinflammatory
      activity.

PMID- 7635170
TI  - Alpha 2-adrenoceptor-mediated vasoconstriction requires a tyrosine kinase.
AB  - alpha 2-adrenoceptor-mediated contractions of the rabbit saphenous vein were
      previously found to be inhibited by wortmannin, a protein kinase inhibitor which
      blocks receptor-dependent phospholipase D activation. Since other studies have
      indicated that receptor-dependent phospholipase D activation required activity of
      a tyrosine kinase, we examined the influence of several tyrosine kinase
      inhibitors on both alpha 2-adrenoceptor-mediated contractions of rabbit saphenous
      vein and alpha 1-adrenoceptor-mediated contractions of rabbit aorta. Methyl 2,5
      dihydroxycinnamate, genistein and erbstatin each caused non-competitive
      inhibition of rabbit saphenous vein contractions elicited by the alpha 2
      adrenoceptor-selective agonist 5-bromo-6-[2-imidazolin-2-yl-amino]-quinoxaline
      (UK14304), yielding complete inhibition at 100 microM and IC50 values of 15, 35
      and 40 microM respectively. By contrast, phenylephrine-induced dose-response
      curves in rabbit aorta were largely unaffected by tyrosine kinase inhibitors at
      50 microM. In a separate analysis of intracellular Ca(2+)-dependent and
      extracellular Ca(2+)-dependent alpha 1-adrenoceptor responses of rabbit aorta,
      genistein (50 microM) did partially reduce the initial intracellular Ca(2+)
      dependent response, but did not reduce maximal response. Methyl 2,5
      dihydroxycinnamate (25 microM) had no effect on intracellular or extracellular
      Ca2+ responses in rabbit aorta. High K(+)-induced contractions of both rabbit
      saphenous vein and aorta were unaffected by up to 100 microM of the tyrosine
      kinase inhibitors. These results indicate an obligatory requirement for tyrosine
      kinase activity in alpha 2-adrenoceptor-mediated but not alpha 1-adrenoceptor
      mediated vasoconstriction.

PMID- 7635171
TI  - Involvement of protein kinase C activation in alpha 2-adrenoceptor-mediated
      contractions of rabbit saphenous vein.
AB  - The role of protein kinase C alpha 2-adrenoceptor-induced contractions of rabbit
      saphenous vein was investigated. Contractions induced by the alpha 2-adrenoceptor
      selective agonist 5-bromo-6-[2-imidazolin-2-ylamino]-quinoline (UK14304) were
      inhibited by prior treatment with pertussis toxin and by Ca2+ removal, confirming
      a Gi/Go-dependent coupling pathway which was highly dependent upon Ca2+ influx.
      Protein kinase C inhibitors calphostin-C and staurosporine each caused a non
      competitive inhibition of UK14304 response. Down-regulation of protein kinase C
      by pretreatment with tetradecanoylphorbol acetate reduced UK14304 response by
      almost 90% with no effect on contractions induced by elevated KCl. The
      ineffectiveness of L-type Ca2+ channel blockers and the absence of stimulated
      45Ca2+ uptake or efflux by UK14304 indicated that phospholipid-derived products
      were most likely responsible for protein kinase C activation. alpha 2
      Adrenoceptor stimulation failed to increase [3H]myoinositol phosphate formation,
      but caused a significant increase in the formation of both [32P]phosphatidic acid
      and diacylglycerol, indicating the possible activation of phospholipase D
      activity. These results suggest that protein kinase C is important for the
      vasoconstriction induced by alpha 2-adrenoceptors and that diacylglycerol derived
      from receptor-initiated phospholipase D activity may provide protein kinase C
      stimulation.

PMID- 7635172
TI  - Effects of levcromakalim and glibenclamide on paced guinea-pig atrial strips
      exposed to hypoxia.
AB  - Isolated strips of guinea-pig atrial myocardium were mounted in isometric
      myographs and electrically paced for measurements of myocardial contractile
      function. Levcromakalim, a K+ channel opener, completely inhibited the
      contractile force in a concentration-dependent way (EC50 = 15 microM).
      Glibenclamide (3 microM), a blocker of ATP-regulated K+ channels (KATP), caused a
      5-fold rightward shift of the concentration-effect curve. Exposure of the atrial
      strips to hypoxia caused a time-dependent loss of contractility from 100% to a
      minimum level of 60% within 12 min. Levcromakalim (1 microM, 3 microM and 10
      microM) concentration-dependently enhanced the hypoxia-induced inhibition of
      contractile function whereas levcromakalim (0.01 microM and 0.1 microM) had no
      significant effect. In the presence of levcromakalim (10 microM) hypoxia reduced
      the contractile force to 25%. Glibenclamide (3 microM) totally antagonized the
      enhancing effect of levcromakalim. When hypoxia was induced in glucose-free Krebs
      solution with 2-deoxyglucose, the myocardial contractility was completely
      suppressed within 12 min. Glibenclamide by itself (3 microM) failed to influence
      the myocardial response to hypoxia both in normal Krebs solution and under
      conditions of impaired glycolysis. The results indicate that levcromakalim by
      activation of myocardial ATP-regulated K+ channels accelerates and enhances the
      hypoxia-induced inhibition of myocardial contractile function. This effect may
      possibly contribute to the mechanism by which K+ channel openers exert
      cardioprotection. The results further suggest that mechanisms different from
      activation of KATP take a major part in the depressant mechanical response to
      hypoxia and glycolytic blockade in the guinea-pig atrial myocardium.

PMID- 7635173
TI  - The effects of suramin on purinergic and noradrenergic neurotransmission in the
      rat isolated tail artery.
AB  - Intracellular microelectrode recording was used to examine the effects of
      suramin, a P2-purinoceptor antagonist, on the electrical responses evoked by
      sympathetic nerve stimulation in the rat isolated tail artery. Field stimulation
      (10 or 20 pulses at 0.5, 1 and 2 Hz) evoked a biphasic electrical response,
      consisting of fast, transient excitatory junctional potentials (e.j.p.s) and a
      slow, prolonged depolarisation. Suramin (100 microM) abolished the e.j.p.s and
      significantly increased the amplitude of the slow depolarisation at all
      frequencies. In contrast, phentolamine (2 microM) abolished the slow
      depolarisation, but had no effect on the magnitude of e.j.p.s. Neither drug
      altered the resting membrane potential of cells. The ability of suramin to
      inhibit e.j.p.s in rat tail artery is consistent with the proposal that it is a
      P2X-purinoceptor antagonist and supports a role for ATP as an excitatory
      cotransmitter from the sympathetic nerves innervating this tissue. Suramin is
      also able to increase the alpha-adrenoceptor-mediated slow depolarisation by an
      unknown mechanism.

PMID- 7635174
TI  - YM-14673, a thyrotropin-releasing hormone analogue, injected into the nucleus
      accumbens and the striatum produces repetitive jaw movements in rats.
AB  - Bilateral injections of the thyrotropin-releasing hormone (TRH) analogue, N alpha
      [((S)-4-oxo-2-azetidinyl)-carbonyl]-L-histidyl-L-prolinamide dihydrate (YM-14673,
      0.1 microgram and 1 microgram/0.2 microliters), into the nucleus accumbens, the
      dorsal and ventrolateral striatum produced repetitive jaw movements in a dose
      dependent manner. The effects were greatest in the nucleus accumbens and smallest
      in the ventrolateral striatum. Pattern of the movements differed from that
      produced by injections of a mixture of SKF 38393 (5 micrograms) and quinpirole
      (10 micrograms); frequent tongue protrusions were evident in rats treated with
      the mixture but those were not seen in YM-14673-treated rats. TRH (1 microgram,
      10 micrograms and 30 micrograms/0.2 microliters) did not evoke jaw movements from
      any of the sites. The non-selective dopamine receptor antagonist, cis-(Z)
      flupentixol (10 micrograms), significantly reduced the response to administration
      of YM-14673 (1 microgram) into the nucleus accumbens or dorsal striatum, while
      the 5-hydroxytryptamine (5-HT)2A receptor antagonist, 2-(2
      dimethylaminoethylthio)-3-phenylquinoline hydrochloride (ICI 169,369, 0.2
      micrograms), did not affect the response to YM-14673 (1 microgram). Given
      intrathecally (0.5 microgram/5 microliters), both YM-14673 and TRH produced wet
      dog shakes. Although the mechanisms giving rise to the display of jaw movements
      after intrastriatal injections of YM-14673 remain unknown, stimulation of the
      dopamine D1/D2 receptors may at least partly contribute to these effects. Anyhow,
      these mechanisms differ from that underlying the ability of YM-14673 and TRH to
      elicit wet-dog shakes, a mechanism that is known to involve serotonergic
      processes.

PMID- 7635175
TI  - In vitro and in vivo effects of cocaine and selected local anesthetics on the
      dopamine transporter.
AB  - The effects of selected local anesthetics on in vitro and in vivo measurements of
      dopamine transporter activity were determined to investigate the role of local
      anesthetic activity in the neuronal actions of cocaine. Cocaine inhibited [3H]2
      beta-carbomethoxy-3-beta-(4-fluorophenyl)tropane 1.5-naphthalenedisulfonate (CFT)
      binding and [3H]dopamine uptake with estimated Ki and IC50 values of 0.6 microM
      and 0.7 micorM, respectively. Of the local anesthetics tested, only dimethocaine
      showed full displacement of CFT binding (0-30 microM tested) and full inhibition
      of dopamine uptake (0-100 microM tested). Dimethocaine was only slightly less
      potent than cocaine with an estimated Ki of 1.4 micorM and an IC50 value of 1.2
      microM for [3H]CFT binding and dopamine uptake. At a maximum concentration of 100
      microM, the ester containing local anesthetics procaine, tetracaine, piperocaine
      and the amide containing local anesthetic dibucaine and bupivacaine partially
      inhibited dopamine uptake by 47-70%. The ester containing local anesthetic
      propoxycaine and the amide containing local anesthetics prilocaine, etidocaine,
      procainamide, and lidocaine inhibited dopamine uptake by 8-30% at 100 microM. A
      10 min administration of cocaine, dimethocaine, or procaine in the dialysis
      solution produced dose-dependent, reversible increases in endogenous dopamine
      efflux from the striata of awake rats. Cocaine and dimethocaine produced similar
      12-fold increases in dialysate dopamine at concentrations of 0.1 mM and 1 mM
      respectively. Procaine (10 mM) produced a 6-fold increase in dialysate dopamine
      while lidocaine (1 mM) produced a reproducible and reversible decrease (30%).
      These results show that the cocaine-like actions of certain local anesthetics
      such as dimethocaine and procaine result from their direct actions of dopamine
      uptake inhibitors.

PMID- 7635176
TI  - Differential ontogenesis of thermal and mechanical antinociception induced by
      morphine and beta-endorphin.
AB  - The antinociceptive effects induced by beta-endorphin and morphine given
      supraspinally have been previously demonstrated to be mediated by the activation
      of different neural mechanisms. The present experiments were to examine the
      effects of intraventricular administration of beta-endorphin and morphine in
      mechanical paw-withdrawal and thermal tail-flick nociceptive tests in rats of 2
      28 days of age. 2-4-day-old neonates were not responsive to i.c.v. injection of
      beta-endorphin or morphine for the inhibition of the tail-flick response. The
      thermal antinociceptive responses induced by beta-endorphin and morphine started
      to develop in 7-14-day-old rats and continued to increase at 21-28 days. The
      inhibition of the mechanical paw-withdrawal response to beta-endorphin was
      already present in 2-day-old rats and morphine in 4-day-old rats. The mechanical
      antinociception progressively increased and reached a plateau at 7 days of age
      for beta-endorphin and 28 days of age for morphine. beta-Endorphin was found to
      be more efficacious than morphine in producing mechanical antinociception. The
      results demonstrate that beta-endorphin- and morphine-induced antinociception to
      mechanical and thermal stimuli develops differently and are consistent with the
      hypothesis that two descending pain inhibitory systems activated by beta
      endorphin and morphine are differentially developed.

PMID- 7635177
TI  - The role of endothelin and nitric oxide in modulation of normal and spastic
      cerebral vascular tone in the dog.
AB  - To investigate the roles of endothelin and nitric oxide (NO) in the regulation of
      cerebral vascular tone under basal conditions and in cerebral vasospasm following
      subarachnoid hemorrhage in dogs, we used BQ-123 (cyclo(-D-Trp-D-Asp-L-Pro-D-Val-L
      Leu-) sodium salt), an endothelin ETA receptor antagonist, L-arginine, a
      substrate for the formation of NO, and NG-nitro-L-arginine methyl ester, an NO
      synthesis inhibitor, and measured the angiographic diameter of the basilar artery
      in vivo. In normal dogs, intracisternal (i.c.) injection of BQ-123 (0.6 mg/kg)
      produced a 29.4 +/- 6.11% (P < 0.01) increase in the basal diameter 24 h after
      injection. NG-nitro-L-arginine methyl ester (0.6 mg/kg i.c.) produced a 19.3 +/-
      2.93% (P < 0.05) decrease in the basal diameter 2 h after injection. This
      decrease was significantly attenuated by both BQ-123 (0.06-0.6 mg/kg i.c.) and L
      arginine (6 mg/kg i.c.), but not by D-arginine. In the two-hemorrhage canine
      model, BQ-123 significantly inhibited the development of cerebral vasospasm (36.9
      +/- 4.11% decrease on day 5 and 42.0 +/- 4.54% decrease on day 6 in controls vs
      21.7 +/- 4.75% decrease (P < 0.05) on day 5 and 20.8 +/- 4.14% decrease (P <
      0.05) on day 6 for 0.6 mg/kg i.c.) significantly attenuated the cerebral
      vasospasm on day 4 from a mg/kg i.c.). Furthermore, in this model, L-arginine (6
      30.9 +/- 5.78% decrease (before)) to a 12.6 +/- 5.99% decrease (after). The
      immunoreactive endothelin-1 levels in the endothelial layer and the adventitia of
      the basilar artery were much higher on days 3 and 7 after the injection of
      autologous blood than on day 0 before blood injection. These results suggest that
      endogenous endothelin and NO both participate in regulating the basal tone of
      cerebral arteries, and, therefore, the development of cerebral vasospasm
      following subarachnoid hemorrhage may be at least partially attributed to an
      impairment of the balanced action of endothelin and NO. Furthermore, endothelin
      ETA antagonists or NO products may be useful in the treatment of cerebral
      vasospasm following subarachnoid hemorrhage.

PMID- 7635178
TI  - mu- and delta-opioid receptor-mediated contractile effects on rat aortic vascular
      smooth muscle.
AB  - The actions of opioid receptor agonists and antagonists were studied in isolated
      rat aortic strips. Morphine (10(-7)-10(-6) M) had no contractile effect on
      resting strips but when added during the relaxation of the contractions induced
      by 10(-9) M noradrenaline, it induced a contractile response which was blocked by
      naloxone. The selective mu-opioid receptor agonist, [D-Ala2,N-Me-Phe4,Gly5
      ol]enkephalin (DAMGO, 10(-7)-10(-6) M), induced an increase in basal tension
      which remained after removal of endothelium or in Ca(2+)-free solution, but was
      inhibited by beta-flunaltrexamine. beta-Flunaltrexamine also inhibited the
      contractile response induced by DAMGO added during the relaxation of the
      contractions induced by noradrenaline. The delta-opioid receptor agonist, [D
      Pen2,D-Pen5]enkephalin, had no effect on resting tension but potentiated the
      contractions induced by noradrenaline; these effects were abolished by
      naltrindol. The selective kappa-opioid receptor agonist, bremazocine, had no
      effect on resting tension and did not modify the amplitude of the contractions
      induced by noradrenaline. These results suggest that, at low concentrations,
      agonists of mu- and delta-opioid receptors may act as modulators of noradrenaline
      induced responses, whereas at higher concentrations, mu-opioid receptor
      stimulation may have a direct contractile effect in isolated rat aorta.

PMID- 7635179
TI  - Use of ER-MP12 as a positive marker for the isolation of murine long-term in
      vitro repopulating stem cells.
AB  - Monoclonal antibody ER-MP12 defines an antigen (Ag) on murine hematopoietic stem
      cells that is differentially expressed by the various subsets in the
      hematopoietic stem cell compartment. To test whether ER-MP12 could be an asset
      for further subfractionation of these subsets, we physically sorted our
      previously defined low-density ER-MP20- (i.e., Ly-6C-) Rhodamine-123dull
      (Rh123dull), and wheat germ agglutinindim (WGAdim) stem cell populations on the
      basis of ER-MP12 Ag expression. In addition, we determined the distribution of
      the ER-MP12 Ag on bone marrow 6 days after 5-FU treatment. Long-term and
      transiently repopulating stem cell subsets were both identified in vitro using
      the cobblestone area-forming cell (CAFC) assay. The data show that sorting on the
      basis of ER-MP12 improves the separation of primitive and more mature stem cell
      subsets in the Rh123dull but not in the WGAdim subpopulation. However, the
      combination of sorting cells on the basis of an intermediate ER-MP12 expression
      and a low WGA affinity (ER-MP12mediumWGAdim) allows an 840-fold enrichment for in
      vitro long-term repopulating cells (day-28 CAFC) when compared with unseparated
      bone marrow. The distribution of the ER-MP12 Ag on 5-FU-treated bone marrow stem
      cells was similar to that in normal bone marrow stem cells, suggesting that the
      level of Ag expression is not dependent on cell-cycle status. Together, the
      combination of ER-MP12 and WGA offers the advantage of a positive selection
      strategy for hematopoietic stem cells, allowing different stem cell subsets to be
      distinguished on the basis of their primitiveness. Since no mature bone marrow
      cells are found within the WGAdimER-MP12medium subpopulation, the combination of
      ER-MP12 and WGA enables hematopoietic stem cells to be highly enriched and thus
      makes the use of a cocktail of lineage-specific antibodies redundant.

PMID- 7635180
TI  - Long-term repopulating abilities of enriched fetal liver stem cells measured by
      competitive repopulation.
AB  - To characterize hematopoietic cell biology, many investigators have used
      protocols that enrich for primitive hematopoietic stem cells (PHSC). In this
      study, we quantified the long-term repopulating ability (LTRA) of enriched and
      discarded fractions of PHSC from day-14 murine fetal liver using the competitive
      repopulation assay. We fractionated populations of fetal cells using the
      antigenic markers AA4.1+, AA4.1+/Sca+, and AA4.1+/Linlow/Sca+. Differentiating
      and repopulating abilities of each of these populations were directly compared
      using competitive repopulation. Adult bone marrow was mixed with fetal cell
      fractions from congenic donors having genetically distinguishable markers, and
      mixtures were given to irradiated recipients. Differentiating and repopulating
      abilities of the enriched donor cells were measured by the proportions of myeloid
      and lymphoid cells having donor markers that repopulated the recipients. LTRA was
      found primarily in the AA4.1+ and AA4.1+/Sca+ subpopulations. Further
      fractionation of the AA4.1+ cells to derive an AA4.1+/Linlow/Sca+ fraction showed
      that virtually all of the long-term stem cell activity was found in this
      subpopulation. These cells were 1400- to 1600-fold enriched in long-term
      functional ability compared to fresh marrow. This very high multilineage
      repopulating ability per cell was directly measured using a long-term functional
      assay in vivo. Importantly, the measured repopulating ability for
      AA4.1+/Linlow/Sca+ cells was about five-fold less than expected from the fraction
      of cells enriched and remained two- to three-fold less even after compensating
      for repopulating ability in discarded fractions. This illustrates that long-term
      functional abilities of enriched PHSC cannot be estimated from fractions enriched
      but should be quantitatively assayed.

PMID- 7635182
TI  - Monocyte chemoattractant protein-1 stimulates tumor necrosis and recruitment of
      macrophages into tumors in tumor-bearing nude mice: increased granulocyte and
      macrophage progenitors in murine bone marrow.
AB  - Monocyte chemoattractant protein-1 (MCP-1) belongs to the newly recognized
      "chemokine" superfamily of activation-inducible cytokines. We report here that
      MCP-1 gene-transferred mouse myeloma cells modulate tumor necrosis in myeloma
      bearing nude mice. We established an MCP-1-producing myeloma cell line (X63-MCP
      1) by transfection with human MCP-1 cDNA as well as interleukin-8-producing X63
      cells (X63 IL-8). Each cell line showed the same growth characteristics in vitro,
      and 1 x 10(7) cells per mouse were injected into the peritoneal cavity resulting
      in the formation of tumors. Hematologic studies, including peripheral white blood
      cell counts and differentiation, showed no differences among the groups. They
      formed tumors in the same manner, which we observed from weeks 2.5 to 9. MCP-1
      mice showed more tumor necrosis and infiltration of the macrophages into the
      tissue surrounding the tumor. In situ hybridization, using a partial cDNA as a
      probe, showed that macrophages contained MCP-1 mRNA. Bone marrow cell colony
      forming assay showed a greater number of both granulocyte and macrophage colonies
      in MCP-1 mouse femur than in those of controls or interleukin-8 mice. MCP-1 has
      no direct stimulatory activity on stem cells, but longer exposure to MCP-1 in
      vivo might stimulate both granulocyte and macrophage progenitors and recruitment
      of macrophages into tumors, and it might explain the antitumor activity of
      macrophages in tumor-bearing nude mice.

PMID- 7635181
TI  - Temporal recovery of short-term repopulating HSC subpopulations in marrow
      following schedule-dependent administrations of IL-1 alpha and M-CSF.
AB  - Studies were carried out to establish the temporal effects of abbreviated
      administrations of IL-1 and IL-1 plus M-CSF as rescue agents on multipotential
      and short-term repopulating hematopoietic stem cell (HSC) subpopulations in
      murine marrow treated with a myelosuppressive dose of 150 mg/kg 5-FU. The
      recovery kinetics for high-proliferative-potential colony-forming cells (HPP
      CFC), CFU-S8 and -S12, and both CFU-M and CFU-G compartments were monitored over
      a 14-day interval in 5-FU-treated bone marrow (FUBM) following daily cytokine
      injections over a 4-day interval. Both IL-1 and the coadministration of IL-1 and
      M-CSF rapidly enhanced the recovery of the HPP-CFC in FUBM to supranormal levels
      and maintained these levels for extended intervals. Moreover, since M-CSF was
      unable to influence the recovery of the HSC subpopulations in FUBM by itself, the
      results of the two cytokines amounted to a synergistic effect on the recovery of
      the HPP-CFC in FUBM and a reduction of severe neutropenia in the myelosuppressed
      animal. Scheduling studies demonstrated that these synergistic effects were
      restricted to those schedules in which M-CSF was coadministered with IL-1 during
      the first 2 days of cytokine rescue. Finally, the recovery curves generated for
      the HSC and CFU-M subpopulations in response to IL-1 (with or without M-CSF) also
      suggest that these cytokines may conceivably alter the normal balance between
      proliferation and differentiation within CFU-S8 and -S12 during the accelerated
      recovery of hematopoiesis in FUBM.

PMID- 7635183
TI  - Matrix molecule interactions with hematopoietic stem cells.
AB  - We have reviewed some aspects of the production, distribution, and organization
      of fibronectin in the bone marrow ECM and discussed HSC-fibronectin interactions.
      Many questions remain. Which isoforms of fibronectin are produced in the bone
      marrow during ontogeny, normal hematopoiesis, and pathophysiologic challenges to
      the marrow microenvironment? Do HSCs interact with ED-A- and ED-B-containing
      fibronectin isoforms the same way they interact with plasma fibronectin? Are
      different fibronectin isoforms selectively expressed in different regions of the
      bone marrow, in keeping with the spatial organization of HSC and hematopoietic
      progenitor cell compartments? Addressing these questions may give us a better
      understanding of the role of fibronectin in HSC localization, proliferation, and
      differentiation. Considerable information regarding the synthesis and secretion
      of other ECM molecules by adherent stromal cells has been derived from in vitro
      analysis of LTBMCs [3]. As with fibronectin, much remains to be learned of the
      precise distribution and composition of bone marrow ECM molecules during in vivo
      development; how in vivo bone marrow ECM secretion, turnover, and remodeling are
      regulated during normal and pathologic hematopoietic states; and the nature and
      importance of in vivo cellular interactions that occur between PHSC and
      individual constituents of the bone marrow ECM.

PMID- 7635184
TI  - Does thalidomide affect IL-2 response and production?
AB  - The exact mechanism of immunosuppression by thalidomide is poorly understood. A
      common denominator in the pathogenesis of graft-vs.-host disease, graft
      rejection, reactional lepromatous leprosy, and autoimmune disorders modulated by
      thalidomide is the activation of T lymphocytes culminating in the synthesis of
      interleukin-2 (IL-2), the expression of high-affinity IL-2 receptors, and the
      induction of proliferation. We investigated the effect of thalidomide on the
      production of IL-2 by the human leukemia cell line Jurkat through induction of IL
      2 gene enhancer activity and through the presence of IL-2 in supernatants. beta
      galactosidase activity, encoded by a reporter lac z construct and controlled by a
      transcription factor in thalidomide-treated PMA- and ionomycin-stimulated Jurkat
      cells, was similar (97 +/- 1.33%; p > 0.1) to non-thalidomide-treated controls at
      all drug concentrations tested. IL-2 enhancer-driven beta-galactose activity of
      thalidomide-treated and stimulated cells was also similar to that of untreated
      controls (p > 0.2). The IL-2 production of activated nontransfected Jurkat cells
      was gauged by using the IL-2-dependent cell line HT-2 as a readout and by ELISA.
      Jurkat cells were subcloned by limiting dilution. Bulk cultures and three
      subclones (J.5.2.5., J.5.2.9., and J.5.3.8.) were assayed at 6, 12, and 24 hours
      after PHA/PMA-induced stimulation. No inhibitory effect on the IL-2 production by
      thalidomide could be detected at any of the drug concentrations tested (5-30
      micrograms/mL), whereas 10 to 100 ng/mL of cyclosporine inhibited the IL-2
      production by 95 to 100%. In addition, we observed neither inhibition of IL-2
      dependent proliferation of HT-2 nor inhibition of PHA-induced proliferation of
      peripheral mononuclear cells by thalidomide at all drug concentrations used (5-30
      micrograms/mL). These results do not support the possibility of a modulatory
      effect on the immune response by thalidomide via IL-2 production and IL-2
      response.

PMID- 7635185
TI  - In vivo biotinylation demonstrates that reticulated platelets are the youngest
      platelets in circulation.
AB  - In both mice and humans, a subset of platelets can be identified that shows
      increased labeling with nucleic acid-specific fluorescent dyes, such as thiazole
      orange. Termed "reticulated platelets," they have been postulated to be platelets
      that have recently entered the circulation. Their numbers appear to reflect the
      rate of new platelet production in a number of clinical and experimental
      situations. To determine whether reticulated platelets really are the youngest
      platelets in circulation and to estimate the length of time that they are
      identifiable after entering the circulation, we have employed a technique of "in
      vivo biotinylation" in mice that labels the entire cohort of circulating cells
      with covalently bound biotin. Blood samples can then be double-labeled with
      fluorescent avidin derivatives and thiazole orange, permitting correlated
      measurement of both surface biotin content and nucleic acid content. The
      biotinylation occurs rapidly, is complete within 30 minutes, is stable for
      several days, and does not appear to alter platelet function. The results show
      that within 24 hours after in vivo biotinylation, platelets appear in the
      circulation with decreased levels of biotinylation and that these are the
      reticulated platelets. The estimated lifespan of reticulated platelets is 1.8
      days, and the lifespan of all platelets by this method is 4.5 days, which is in
      agreement with estimates made by other methods.

PMID- 7635186
TI  - Active site residues in m-calpain: identification by site-directed mutagenesis.
AB  - Site-directed mutagenesis was used to alter putative active site residues in the
      large subunit of calpain, and the activity of the mutants was measured following
      coexpression in E. coli of both calpain subunits and purification of the
      resultant dimers. Mutants Cys105Ser, His262Ala and Asn286Ala had no activity.
      Together with sequence comparisons among cysteine proteinases, the results
      suggest that these residues constitute the catalytic triad in calpain. Mutants
      Asn286Asp and Trp288Tyr had low activity, consistent with interaction of these
      residues with His262.

PMID- 7635189
TI  - The nuclear pore-targeting complex binds to nuclear pores after association with
      a karyophile.
AB  - We recently showed that a karyophilic protein forms a stable complex, termed
      nuclear pore-targeting complex (PTAC), with cytoplasmic components prior to
      nuclear pore-binding. In this study, we cloned a cDNA encoding a 97 kDa of PTAC
      (PTAC97). Recombinant PTAC97 completely reconstitutes the nuclear binding-step in
      conjunction with a 58 kDa component of PTAC (PTAC58) in the semi-intact cell-free
      transport assay. Biochemical analysis reveals that PTAC58 binds to a karyophilic
      protein, and PTAC97 is associated with PTAC58 in a 1:1 molar ratio. A complex of
      PTAC97 and PTAC58 targets nuclear pores, depending on the presence of a
      karyophile. These in vitro results suggest that the first step in nuclear import
      occurs through the targeting-complex formation of a karyophile with PTAC58 bound
      to PTAC97.

PMID- 7635187
TI  - Endogenous cardiac Ca2+ channels do not overcome the E-C coupling defect in
      immortalized dysgenic muscle cells: evidence for a missing link.
AB  - The expression of subunit genes of the Ca2+ channel complex was studied in
      differentiating, immortalized mouse mdg cells. These cells expressed alpha 1 and
      alpha 2/delta transcripts of the skeletal muscle Ca2+ channel genes, a cardiac
      Ca2+ channel alpha 1 subunit gene and several known transcript variants of
      skeletal, cardiac and brain beta genes. The mdg mutation is retained in the
      129DA3 cell line and occurs exclusively at nucleotide position 4010 in the
      skeletal alpha 1 transcript in which a cytosine residue is deleted. In early
      stages of differentiation and fusion, Ba2+ currents were detected in dysgenic
      myotubes the same as the cardiac L-type Ca2+ channel. These data provide specific
      structural evidence [Chaudhari, N. (1992) J. Biol. Chem. 267, 25636-25639] for
      the major genetic defect in mouse muscular dysgenesis and show a change in the
      expression levels of alpha 1S and alpha 1C. The upregulation of the expression of
      alpha 1C results in functional Ca2+ channel activity, however, presumably not
      sufficient for excitation-contraction coupling.

PMID- 7635188
TI  - Effects of protein kinase inhibitors and protein phosphatase inhibitors on cyclic
      AMP-dependent down-regulation of vesicular monoamine transport in
      pheochromocytoma PC12 cells.
AB  - Cyclic AMP down-regulates vesicular monoamine transport in PC12 cells and thereby
      decreased catecholamine reuptake from the extracellular fluid. We examined the
      effects of protein kinase inhibitors and protein phosphatase inhibitors on this
      cAMP action. Treatment of cells with a protein kinase inhibitor, K252a, increased
      vesicular amine transport and cellular amine uptake, thereby antagonizing the
      regulatory action of cAMP. In contrast, a protein phosphatase inhibitor, okadaic
      acid, had the opposite effect on the amine transport, i.e. it enhanced the cAMP
      action. These results suggest the involvement of a protein phosphorylation
      process in the cAMP-dependent modulation of vesicular monoamine transport.

PMID- 7635190
TI  - Cloning of boar SPMI gene which is expressed specifically in seminal vesicle and
      codes for a sperm motility inhibitor protein.
AB  - Boar semen contains a seminal plasma motility inhibitor (SPMI) that blocks the
      motility of demembranated-reactivated spermatozoa as well as of intact
      spermatozoa. In this paper, we describe the primary structure of SPMI, the coding
      of boar SPMI cDNA gene and its expression in various porcine tissues. Nucleotide
      sequence analysis of the 645-bp SPMI cDNA predicts a coded polypeptide of 137
      amino acid residues which includes a 21-residue signal peptide and a 116-residue
      secreted protein. The amino acid sequence of SPMI was found to be highly
      homologous to AQN-3, a member of spermadhesin family proteins of boar that bind
      to spermatozoa. Expression of the boar SPMI gene detected by Northern blot
      analysis revealed that its expression is very abundant in seminal vesicles and
      specific to this tissue.

PMID- 7635192
TI  - The crystal structure of apo-pseudoazurin from Alcaligenes faecalis S-6.
AB  - The 3D structure of the apo-pseudoazurin (copper free pseudoazurin) from
      Alcaligenes faecalis strain S-6 is determined and refined at pH 6.7 using X-ray
      diffraction data to 1.85 A resolution. The final crystallographic R-factor is
      0.164. Comparing the structures of apo-pseudoazurin and the native (Cu2+)
      protein, we observed limited differences ranging between 0.1-0.4 A at the
      vicinity of the copper site, at the loops connecting the secondary structural
      elements, at certain beta-strands and at the amino and carboxy termini of the
      protein.

PMID- 7635191
TI  - Lipid biosynthetic genes and a ribosomal protein gene are cotranscribed.
AB  - By using insertional mutagenesis we demonstrated that the rpmF gene encoding
      ribosomal protein L32, the plsX gene encoding a protein involved in membrane
      lipid synthesis and several fatty acid biosynthetic genes (fabH, fabD and fabG)
      are cotranscribed. Organization of these genes into an operon may play a role in
      the coordinate regulation of the synthesis of ribosomes and the cell membranes.

PMID- 7635193
TI  - Conserved ATPase and luciferase refolding activities between bacteria and yeast
      Hsp70 chaperones and modulators.
AB  - We have reconstituted an ATP-dependent protein folding machinery using purified
      yeast cytosolic proteins. The S. cerevisiae Hsp70 Ssa1p and the DnaJ homolog
      Ydj1p refolded denatured firefly luciferase. In E. coli, efficient refolding of
      luciferase requires the Hsp70 DnaK and two modulators, DnaJ and GrpE, that
      synergistically stimulate its ATPase activity. Exchanging DnaJ homologs between
      the S. cerevisiae and E. coli systems revealed that their ability to stimulate
      Hsp70 ATPase activity was conserved. In contrast, GrpE further stimulated only
      DnaK's ATPase activity. Efficient refolding of luciferase by Ssa1p and DnaJ, but
      not by DnaK and Ydj1p, suggests that a compatible Hsp70/DnaJ homolog pair can act
      as a protein folding machinery.

PMID- 7635194
TI  - Demonstration of segmental mobility in the functionally essential carboxyl
      terminal part of ribonucleotide reductase protein R2 from Escherichia coli.
AB  - The C-terminus of protein R2 is important for the formation of the enzymatically
      active complex between proteins R1 and R2 of ribonucleotide reductase from
      Escherichia coli. Some residues in this part of R2 may also be involved in
      intramolecular electron transfer. We now demonstrate that 26 amino acid residues
      at C-terminus of protein R2 are mobile in the free protein, and can be studied by
      1H NMR. Spectral assignment of narrow resonances was made by comparison of TOCSY
      and NOESY spectra from wild-type R2 with corresponding spectra of a mutant
      protein R2, lacking 30 residues at the carboxyl terminus.

PMID- 7635195
TI  - Cloning and characterization of a novel rat alcohol dehydrogenase of class II
      type.
AB  - A class II type alcohol dehydrogenase from rat liver was characterized at the
      cDNA level after screening cDNA libraries in combination with PCR amplification
      of the 5'-part. The open reading frame translates into a polypeptide of 376 amino
      acid residues, which show 73% positional identity to the human class II enzyme.
      This suggests that the class II enzyme is the most variable form of the mammalian
      alcohol dehydrogenases. A deletion is apparent corresponding to position 294 of
      the human enzyme and amino acid residues unique to the rat protein of those
      interacting with the coenzyme NAD+ are found at positions 47, 51, 178, and 271.
      Position 47 is occupied by Pro instead of Arg or His found in most mammalian
      alcohol dehydrogenases. This exchanged residue will not hydrogen bond to the
      pyrophosphate of the coenzyme and will change the local environment around
      position 47 to strictly hydrophobic.

PMID- 7635196
TI  - Decreased thermal stability of red blood cell glu100-->gly superoxide dismutase
      from a family with amyotrophic lateral sclerosis.
AB  - Familial amyotrophic lateral sclerosis is a degenerative motor neuron disease
      associated in some cases with the presence of a mutant form of Cu/Zn superoxide
      dismutase. We have studied the stability of the gly100-->glu mutant in extracts
      of red cells obtained from members of a family with a history of the disease.
      Extracts containing the mutant had an average 68% of normal superoxide dismutase
      activity. On heating at 65 degrees C, these extracts lost activity at twice the
      rate of extracts containing only the normal enzyme. Decreased heat stability was
      also evident on native polyacrylamide gel electrophoresis with activity staining.
      This showed selective loss of first the mutant homodimer and then the heterodimer
      of the enzyme. Decreased stability intracellularly could be a factor in motor
      neuron degeneration.

PMID- 7635197
TI  - Separation of phospho- and non-phosphopeptides using reverse phase column
      chromatography.
AB  - Peptides containing phosphoserine, phosphothreonine or phosphotyrosine and their
      parent non-phosphorylated forms were chromatographed using standard C18 reverse
      phase chromatography in the presence of a water/acetonitrile gradient
      supplemented with different counter ions. We obtained the best separation of
      phosphorylated from non-phosphorylated peptides in the presence of
      heptafluorobutyric acid, with differences in retention times as large as
      approximately 20 min. The chromatographic method was reliable in separation of
      the same peptides phosphorylated at different positions, acidic or basic phospho
      Ser/Thr-peptides or phospho-Tyr-containing peptides. The described separation
      conditions are useful in studying the kinetics of
      phosphorylation/dephosphorylation and in analysis of phosphorylation sites in
      vivo.

PMID- 7635198
TI  - Identification of two highly homologous presynaptic proteins distinctly localized
      at the dendritic and somatic synapses.
AB  - Through screening of a murine brain cDNA library, we have isolated two brain
      specific cDNAs encoding highly homologous proteins, named 921-L and 921-S,
      comprised of 134 amino acids with 80% identity. Immunohistological study with the
      mAbs raised against the bacterially expressed 921 proteins showed that 921-L
      protein is distributed at the dendritic region and 921-S at the neuronal somatic
      surface. Immuno-electron microscopic study revealed that both 921 proteins are
      localized at the presynaptic terminal, indicating that the 921 proteins are
      differentially expressed at the dendritic and somatic presynapses.

PMID- 7635199
TI  - Cloning, sequencing and functional expression of an acetylcholinesterase gene
      from the yellow fever mosquito Aedes aegypti.
AB  - A degenerate PCR strategy was used to isolate a fragment of the
      acetylcholinesterase gene (Ace) homolog from Aedes aegypti and screen for a cDNA
      clone containing the complete open reading frame of the gene. The predicted amino
      acid sequence of the Aedes gene shares 64% identity with Ace from Drosophila and
      87% identity with the acetylcholinesterase gene from another mosquito species
      Anopheles stephensi. High levels of expression of the Aedes gene were achieved by
      infection of Sf21 cells with a recombinant baculovirus containing the Aedes Ace
      cDNA. The catalytic properties and sensitivity of the recombinant enzyme to
      insecticide inhibition are described and discussed in relation to the role of
      insensitive AChE in conferring resistance to organophosphorus and carbamate
      insecticides.

PMID- 7635200
TI  - Extracellular release of the 'differentiation enhancing factor', a HMG1 protein
      type, is an early step in murine erythroleukemia cell differentiation.
AB  - Differentiation enhancing factor (DEF) is a 29 kDa protein expressed in murine
      erythroleukemia (MEL) cells and active in promoting a significant increase in the
      rate of hexamethylenebisacetamide induced differentiation of these cells. The
      factor was recently shown to possess an amino acid sequence identical to that
      reported for one of the HMG1 proteins, designated as 'amphoterin' on the basis of
      its highly dipolar sequence. In the present study, we have expressed DEF cDNA in
      an E. coli strain and found that the recombinant protein has functional
      properties identical to those observed with native DEF. Furthermore, we
      demonstrate that, following MEL cell stimulation with the chemical inducer, DEF
      is secreted in large amounts in the extracellular medium. In fact, the N-terminal
      sequence and the partial amino acid sequence of tryptic peptides from the
      secreted protein correspond to those of DEF isolated from the soluble fraction of
      resting MEL cells. These results are indicative for an extracellular localization
      as the site of action of DEF and suggest a novel function for proteins belonging
      to the HMG1 family. Finally, the early decay of DEF mRNA, in chemical induced MEL
      cells, support the hypothesis that the involvement of the enhancing factor occurs
      and is completed in the early phases of cell differentiation.

PMID- 7635201
TI  - Unique reactive site domains of neuroendocrine isoforms of alpha 1
      antichymotrypsin from bovine adrenal medulla and pituitary revealed by molecular
      cloning.
AB  - Molecular cloning of bovine adrenal medulla (AM) and pituitary (Pit) alpha 1
      antichymotrypsin cDNAs indicated novel isoforms of ACT. The deduced primary
      sequences indicated that the AM ACT and Pit ACT possess COOH-terminal reactive
      site domains that are characteristic of serpins (serine protease inhibitors). Of
      high interest was the finding of unique reactive sites within AM ACT and Pit ACT
      which are predicted to possess Arg as P1 residue. Arginine as P1 residue
      parallels the cleavage specificity of neuroendocrine prohormone processing
      enzymes cleaving at basic residues. Furthermore, RT-PCR indicated tissue-specific
      expression of AM and Pit ACT mRNAs. The AM and Pit isoforms of ACT may regulate
      novel target proteases involved in neuroendocrine function.

PMID- 7635202
TI  - Clear differences in ceramide metabolism between glycosphingolipids and
      sphingomyelin in a human promyelocytic leukemia cell line HL-60 stimulated by a
      differentiation inducer.
AB  - Although the ceramide components of both glycosphingolipids (GSLs) and
      sphingomyelin (SM) in HL-60 cells were identical, the molecular species of the
      ceramides preferentially used in biosynthesis were quite different in GSLs and
      SM. When HL-60 cells were stimulated to differentiate into macrophage-like cells
      by phorbol ester after their sphingolipids had been metabolically labeled with L
      [3-14C]serine to saturation point, marked changes in the radioactivities of the
      ceramide residues were observed in GSLs, showing the activation of a biosynthetic
      pathway of ganglioside GM3. No significant changes were, however, observed in the
      ceramide residues of SM. These results indicate that it is necessary to consider
      the overall metabolism of ceramides, including their origin, when investigating
      the functions of ceramides in signal transduction systems.

PMID- 7635203
TI  - Structural role of disulfide bridges in the cyclic ADP-ribose related
      bifunctional ectoenzyme CD38.
AB  - Human CD38, a type II cell surface glycoprotein, is a bifunctional ectoenzyme
      catalyzing both ADP-ribosyl cyclase and cyclic ADP-ribose (cADPR) hydrolase
      reactions. It shares a high degree of sequence homology with the cyclase from
      Aplysia species and studies of site-directed mutagenesis have recently
      demonstrated the importance, but not elucidated the role, of several cysteine
      residues highly conserved between these proteins. N-Ethylmaleimide, iodoacetamide
      and thiol-oxidizing reagents failed to affect either the cyclase or the weaker
      hydrolase activity of the Aplysia californica protein. Likewise, these reagents
      did not impair the two activities of CD38 purified from human erythrocytes. beta
      mercaptoethanol had no effect on the Aplysia enzyme activities, while it
      inactivated both the cyclase and the cADPR hydrolase of CD38 by inducing its
      extensive oligomerization. In intact erythrocytes the beta-mercaptoethanol
      dependent enzyme inactivation was completely prevented by prior cross-linking of
      the membrane proteins with glutaraldehyde. These data demonstrate that none of
      the cysteine residues plays any direct catalytic role in CD38 and Aplysia
      proteins, and that disulfide bridges are essential for maintaining the monomeric,
      catalytically active structure of CD38.

PMID- 7635204
TI  - Molecular cloning of cDNA for sapecin B, an antibacterial protein of Sarcophaga,
      and its detection in larval brain.
AB  - A cDNA clone for sapecin B, an antibacterial protein of Sarcophaga, was isolated.
      This cDNA encoded a precursor protein of sapecin B consisting of a signal
      sequence (24 residues), prosegment (30 residues) and mature sapecin B (34
      residues). Sapecin B was synthesized almost exclusively in the fat body when the
      larval body wall was injured, but the brain of naive larvae was also demonstrated
      to contain a significant amount of sapecin B. These findings suggested that
      sapecin B is a bifunctional protein.

PMID- 7635205
TI  - Effects of fasting and refeeding on ob gene expression in white adipose tissue of
      lean and obese (oblob) mice.
AB  - A 33-mer antisense oligonucleotide has been utilized as a probe for the rapid
      chemiluminescence-based detection of ob (obese) mRNA. Expression of the ob gene
      was evident in several white adipose tissue depots of mice (epididymal, highest;
      subcutaneous and omental, lowest), but not in other organs. Fasting (24 h)
      induced a substantial fall in ob mRNA in the epididymal fat of lean mice, which
      was rapidly reversed on refeeding, responses consistent with the putative role of
      ob in energy balance. Fasting had no effect, however, on ob mRNA levels in obese
      (oblob) mice.

PMID- 7635206
TI  - Baculovirus-driven expression and purification of glycine receptor alpha 1 homo
      oligomers.
AB  - The glycine receptor is a ligand-gated anion channel protein of postsynaptic
      membranes. We expressed a homo-oligomeric receptor composed of human alpha 1
      subunits in Spodoptera frugiperda cells by infection with a recombinant
      Autographa californica nuclear polyhedrosis virus. A substantial fraction of the
      recombinant receptor was incorporated as a functional channel protein into the
      cell's plasma membrane at expression levels 4- to 30-fold higher than in other
      eukaryotic heterologous expression systems or native rat spinal cord membranes,
      respectively. Upon detergent solubilization, the alpha 1 receptor was found to
      exist in a predominantly monodisperse state and could be affinity-purified to
      near homogeneity. This preparation is a potential starting point for future
      crystallisation studies.

PMID- 7635208
TI  - The mature AEP2 gene product of Saccharomyces cerevisiae, required for the
      expression of subunit 9 of ATP synthase, is a 58 kDa mitochondrial protein.
AB  - The nucleotide sequence of the yeast nuclear AEP2 gene, required for the
      expression of the mitochondrial DNA-encoded subunit 9 of ATP synthase, predicts a
      primary translation product of 67.5 kDa. The ATP13 gene is allelic to AEP2 but
      was reported to encode a protein of about 42 kDa in size. We thus investigated
      genetically and biochemically the size of the AEP2 gene product. Genetic
      complementation assays using 3' truncated AEP2 genes, here shows that function is
      abolished by the removal of only 32 amino acids from the C-terminus of the
      predicted protein product. Cell-free translation of AEP2 produces a 64 kDa
      polypeptide (consistent with the AEP2 sequence) which is imported into
      mitochondria and processed to a 58 kDa product by the removal of a presequence of
      about 50 amino acids.

PMID- 7635207
TI  - Novel actin crosslinker superfamily member identified by a two step degenerate
      PCR procedure.
AB  - Actin-crosslinking proteins link F-actin into the bundles and networks that
      constitute the cytoskeleton. Dystrophin, beta-spectrin, alpha-actinin, ABP-120,
      ABP-280, and fimbrin share homologous actin-binding domains and comprise an actin
      crosslinker superfamily. We have identified a novel member of this superfamily
      (ACF7) using a degenerate primer-mediated PCR strategy that was optimized to
      resolve less-abundant superfamily sequences. The ACF7 gene is on human chromosome
      1 and hybridizes to high molecular weight bands on northern blots. Sequence
      comparisons argue that ACF7 does not fit into one of the existing families, but
      represents a new class within the superfamily.

PMID- 7635209
TI  - Characterization of the testis-specific gene 'calmegin' promoter sequence and its
      activity defined by transgenic mouse experiments.
AB  - We have cloned the genomic DNA of calmegin [(1992) J. Biol. Chem. 269, 7744-7749]
      and analyzed its promoter region. It contained GC-rich sequences and potential
      binding sites for AP 2 and Sp 1, but lacked the TATA sequence. The 330 bp 5'
      flanking sequence of calmegin genomic DNA fused with the CAT gene was used for
      the study of promoter activity in transgenic mice. The CAT gene activity was
      detected exclusively in testes, indicating that the 330 bp calmegin 5' sequence
      was sufficient for the testis-specific expression. The existence of testicular
      nuclear factors specifically bound to the putative promoter sequence was also
      demonstrated.

PMID- 7635210
TI  - Prooxidant iron and copper, with ferroxidase and xanthine oxidase activities in
      human atherosclerotic material.
AB  - Low density lipoproteins are highly sensitive to oxidation by copper salts, and
      such peroxidation is accompanied by macrophage scavenger receptor recognition.
      This study shows that fresh human atherosclerotic material (aneurysms and
      endarterectomies) can contain detectable amounts of redox active iron and copper
      that is chelatable from tissue homogenates. Such material is often prooxidant
      towards lipid peroxidation and deoxyribose degradation. Aneurysms and
      endarterectomies contain ferroxidase 1 activities, whereas only in aneurysms
      could caeruloplasmin be immunologically detected. Ferroxidase 2 activity,
      characteristic of a copper-oxidised lipoprotein complex, could not, however, be
      detected in any of the atherosclerotic samples. A third ferroxidase activity,
      attributable to xanthine oxidase, was present in several aneurysms and
      endarterectomies.

PMID- 7635212
TI  - Characterization of the dynamic properties of Rhodobacter capsulatus
      ferricytochrome c'--a 28 kDa paramagnetic heme protein.
AB  - The cytochrome c' are paramagnetic heme proteins generally consisting of two
      identical 14 kDa subunits. The recent assignment of the 1H and 15N resonances of
      the Rhodobacter capsulatus ferricytochrome c' has allowed characterization of the
      dynamic properties by measurement of the heteronuclear NOE for each resolved
      amide group. The relative importance of fast local motion and paramagnetic effect
      on nuclear relaxation were distinguished by comparison of the measured
      heteronuclear NOE with that of the overall experimental average. We show that the
      average experimental value of -0.16 corresponds to the rigid body motion expected
      for a spherical complex of 28 kDa. Residues 3-5, 50-55 and 69-70 exhibit
      decreased heteronuclear NOE due to local motions on a fast time scale with
      respect to molecular tumbling. Based on the X-ray crystal structure of the
      homologous cytochrome c' from Chromatium vinosum, the mobile regions correspond
      to the N-terminus of helix-1 and 2 regions of nonregular secondary structure
      located between helices-2 and -3.

PMID- 7635211
TI  - Determination of the affinity of talin and vinculin to charged lipid vesicles: a
      light scatter study.
AB  - Recent experimental findings have demonstrated that both talin and vinculin bind
      to phospholipids and insert into the hydrophobic region of lipid membranes. Here,
      we show that the light scatter method can be used for measuring the affinity of
      proteins to phospholipid membranes. Large unilamellar DMPC/DMPG vesicles were
      produced by the extrusion technique (LUVETs). We have used repeated
      heating/cooling scans between 15 degrees C and 35 degrees C to ensure protein
      lipid interaction/insertion. A molar affinity of talin, K = 2.9 x 10(6) M-1 and
      of vinculin, K = 3.3 x 10(5) M-1 to lipid vesicles, respectively, was determined
      from the plot; light scatter signal at 380 nm against protein concentrations by
      fitting the term, ln (Io/I-1) = A-K x c to the data.

PMID- 7635213
TI  - The highly conserved methionine of subunit I of the heme-copper oxidases is not
      at the heme-copper dinuclear center: mutagenesis of M110 in subunit I of
      cytochrome bo3-type ubiquinol oxidase from Escherichia coli.
AB  - A common feature within the heme-copper oxidase superfamily is the dinuclear heme
      copper center. Analysis via extended X-ray absorption fine structure (EXAFS) has
      led to the proposal that sulfur may be bound to CuB, a component of the dinuclear
      center, and a highly conserved methionine (M110 in the E. coli oxidase) in
      subunit I has been proposed as the ligand. Recent models of subunit I, however,
      suggest that this residue is unlikely to be near CuB, but is predicted to be near
      the low spin heme component of the heme-copper oxidases. In this paper, the role
      of M110 is examined by spectroscopic analyses of site-directed mutants of the bo3
      type oxidase from Escherichia coli. The results show that M110 is a non-essential
      residue and suggest that it is probably not near the heme-copper dinuclear
      center.

PMID- 7635214
TI  - Functional domain and poly-L-proline II conformation for candidacidal activity of
      bactenecin 5.
AB  - The functional domain for candidacidal activity of bactenecin 5 has been
      determined by synthesizing bactenecin 5 and its fragments [1-22 (BN22), 7-22
      (BN16) and 20-43 (BC24)]. The N-terminal sequence BN16 retained the candidacidal
      potency of the parent molecule and this region appears to be the candidacidal
      domain. The circular dichroism spectra of these peptides indicate the presence of
      largely poly-L-proline II conformations in aqueous solutions and in lipid
      vesicles. The coupling constant (JNH-C alpha H) values, and a set of medium- and
      short-range nuclear Overhauser effects observed for the N-terminal peptide (BN16)
      in the two-dimensional nuclear magnetic resonance suggest that poly-L-proline II
      helix could be the biologically active conformation.

PMID- 7635215
TI  - ADP release is the rate-limiting step of the MT activated ATPase of non-claret
      disjunctional and kinesin.
AB  - The motor protein non-claret disjunctional (ncd) moves towards the minus ends of
      microtubules (MTs), whereas its close relative kinesin moves in the opposite
      direction towards the plus ends of MTs. The mechanisms of movement and
      directional reversal for these motor proteins are unknown. Here we report the
      rate constants for MT activated ADP release from a recombinant double-headed ncd
      protein, GST-MC5, and a recombinant double-headed kinesin protein, K delta 401,
      measured using the fluorescent nucleotide analogues methylanthranilyol ATP
      (mantATP) and mantADP. Comparison of the maximal MT activated mantADP release
      rates for these proteins with their maximal MT activated mantATP turnover rates
      indicates that ADP release is the rate-limiting step for ATP turnover for both
      ncd and kinesin. This data supports the view that directional reversal may result
      from structural rather than chemical kinetic differences in the way the motors
      interact with MTs.

PMID- 7635216
TI  - Rhizobium tropici nodulation factor sulfation is limited by the quantity of
      activated form of sulfate.
AB  - Rhizobium tropici is a broad host-range symbiont of Phaseolus vulgaris. This
      bacterium produces a mixture of sulfated and non-sulfated N-methylated pentameric
      nodulation (Nod) factors. To understand the genetic bases of the partial
      sulfation of R. tropici Nod factors, which might be involved in the broad host
      range of this species, we introduced in R. tropici CFN299 the recombinant plasmid
      pGMI515 carrying a set of nodulation (nod) genes of R. meliloti, including those
      involved in the sulfation of R. meliloti Nod factors. The CFN299 (pGMI515)
      transconjugant produced only sulfated Nod factors, but approximately half of them
      were no more N-methylated. Mutations in R. meliloti nodH gene did not decrease
      the Nod factor sulfation whereas inactivation of the nodPQ genes restored the
      production of a mixture of sulfated and non-sulfated molecules. These results
      suggest that the limiting step in R. tropici Nod factor sulfation is the
      production of activated sulfate donors. Mutations in the R. meliloti nodFEG and
      nodH genes did not change the N-methylation pattern, whereas mutations in nodPQ
      increased the degree of N-methylation, suggesting a metabolic link between
      sulfation and methylation of R. tropici Nod factors.

PMID- 7635217
TI  - Human and other mammalian genomes contain transposons of the mariner family.
AB  - Internal fragments of the putative transposase gene of mariner-like elements
      (MLEs) were amplified from human, mouse, rat, chinese hamster, sheep and bovine
      genomic DNAs by polymerase chain reaction (PCR). The sequences identified in
      human, ovine and bovine genomes correspond to ancient degenerate transposons.
      Screening mammalian sequence libraries identified a truncated element in the
      human ABL gene and the sequence of its 5'-ITR was determined. This ITR sequences
      were used in PCR experiments with DNA from six mammalian species and detected
      full-sized and deleted MLEs. The presence of MLE in mammalian genomes
      demonstrates that they are ubiquitous mobile elements found from fungi to man.
      This observation strongly raises the possibility that MLE could constitute tools
      for the modification of eucaryotic genomes.

PMID- 7635218
TI  - The basal level of transcription of the alc genes in the ethanol regulon in
      Aspergillus nidulans is controlled both by the specific transactivator AlcR and
      the general carbon catabolite repressor CreA.
AB  - In the A. nidulans ethanol utilization pathway, specific induction is mediated by
      the transactivator AlcR which is subject to strong positive autogenous regulation
      and activates the transcription of the two structural genes alcA and aldA. Carbon
      catabolite repression is mediated by CreA which represses directly the
      transacting gene alcR and the two structural genes. We show here that the basal
      expression of the alcR and alcA genes is also controlled by the two regulatory
      circuits, positively by the transactivator AlcR and negatively by the repressor
      CreA, the aldA gene being subject only to the control of the CreA repressor.

PMID- 7635219
TI  - Acid destabilization of a triple-helical peptide model of the macrophage
      scavenger receptor.
AB  - Electrostatic interactions were studied in a triple-helical peptide,
      (POG)3PKGQKGEKG(POG)4, which contains a lysine-rich 9 residue sequence from the
      collagen-like domain of the macrophage scavenger receptor (MSR). This peptide
      adopts a stable triple-helical conformation only when the pH is higher than 4.5,
      corresponding to ionization of the Glu side chain. Modeling shows Glu forms ion
      pairs with one of the Lys residues, stabilizing the structure. Previously studied
      collagen-like peptides show relatively small contributions of electrostatic
      interactions to stability. The large magnitude of the pH mediated structural
      changes seen for this peptide suggests that specific placement of charged
      residues in the triple-helix conformation can generate strong electrostatic
      interactions.

PMID- 7635220
TI  - Differential cytokine modulation of the genes LAMA3, LAMB3, and LAMC2, encoding
      the constitutive polypeptides, alpha 3, beta 3, and gamma 2, of human laminin 5
      in epidermal keratinocytes.
AB  - Laminin 5, an anchoring filament protein previously known as
      nicein/kalinin/epiligrin, consists of three polypeptide chains, alpha 3, beta 3,
      and gamma 2, encoded by the genes LAMA3, LAMB3, and LAMC2, respectively. The
      expression of laminin 5 was detected by Northern hybridization with specific cDNA
      probes in various epidermal keratinocyte cultures, whereas no expression of any
      of the three genes could be detected in foreskin fibroblast cultures.
      Transforming growth factor-beta (TGF-beta) enhanced LAMA3, LAMB3, and LAMC2 gene
      expression in human epidermal keratinocytes, as well as in HaCaT and Balb/K cells
      in culture, although the extent of enhancement was greater for LAMA3 and LAMC2
      genes than for LAMB3. Interestingly, tumor necrosis factor-alpha, (TNF-alpha)
      alone did not alter the expression of LAMB3 and LAMC2 genes in human epidermal
      keratinocytes, whereas it inhibited the expression of LAMA3. These results
      suggest that the expression of the three genes encoding the laminin 5 subunits is
      not coordinately regulated by the cytokines tested.

PMID- 7635221
TI  - Effect of polyethylene glycol on the activity, intrinsic fluorescence, and
      oligomeric structure of castor seed cytosolic fructose-1,6-bisphosphatase.
AB  - The effect of polyethylene glycol (PEG) on the activity, intrinsic fluorescence,
      and oligomeric structure of homogeneous cytosolic fructose-1,6-bisphosphatase
      (FBPasec) from endosperm of germinating castor oil seeds has been examined.
      Increasing the PEG concentration in the FBPasec reaction mixture elicited a
      progressive 3-fold decrease in the enzyme's Km for fructose-1,6-P2. The presence
      of PEG also: (i) increased the extent of FBPasec inhibition by high levels of
      fructose-1,6-P2, (ii) enhanced the intensity of the enzyme's fluorescence
      emission spectra, and (iii) prevents dissociation of the active tetrameric native
      enzyme into inactive lower M(r) forms during gel filtration HPLC. It is concluded
      that the activity and structure of plant FBPasec is modified by extreme dilution,
      probably as a result of partial deaggregation of the native tetrameric enzyme.

PMID- 7635222
TI  - Disposition of the carboxy-terminus tail of rabbit lactase-phlorizin hydrolase
      elucidated by phosphorylation with protein kinase A in vitro and in tissue
      culture.
AB  - The intracellular disposition of the carboxy-terminus tail of rabbit lactase
      phlorizin hydrolase (LPH) is demonstrated, using a specific phosphorylation of
      Ser1916 by protein kinase A (PKA). This phosphorylation is shown to occur not
      only in vitro (with pure LPH and pure catalytic subunit of PKA), but also in an
      organ culture of the small intestine. Cholera toxin, which is known to act in
      vivo on the membranes of the small intestine, with severe clinical consequences,
      and to elevate the intracellular cyclic AMP of enterocytes, is shown to enhance
      significantly the phosphorylation of LPH in intact cells grown as an organ
      culture. These findings establish the cytosolic orientation of the carboxy
      terminus tail of LPH in situ, and raise the possibility that the tail itself and
      its phosphorylation by PKA may have a physiological or physiopathological
      significance.

PMID- 7635223
TI  - Management of ovarian cysts in menopausal women.

PMID- 7635225
TI  - Management of breech presentation: the 1993 Israeli census.
AB  - OBJECTIVES: To investigate current attitudes to management of labor and delivery
      in pregnancies complicated by breech presentation. STUDY DESIGN: A questionnaire
      was sent to the directors of 23 units of maternal-fetal medicine, all members of
      the Israel Society of Perinatal Obstetricians. The survey included 69,072
      deliveries in the year 1993. Current world literature on the topics included in
      the survey was also reviewed. RESULTS: The overall response rate was 83% (19/23).
      The overall breech presentation rate was 3.4%, and overall caesarean section rate
      was 11.2%. In breech presentation, the caesarean section rate was 63.6%.
      CONCLUSIONS: A rational approach allows vaginal breech delivery to be practiced
      in almost half of carefully selected cases. These results again emphasize the
      longstanding need for prospective randomized studies regarding the different
      aspects associated with the delivery of the fetus in breech presentation.

PMID- 7635224
TI  - Antenatal risk factors for germinal matrix hemorrhage and intraventricular
      hemorrhage in preterm infants.
AB  - OBJECTIVES: This study was designed to evaluate the effect of antenatal risk
      factors on the occurrence of germinal matrix hemorrhage or intraventricular
      hemorrhage in preterm infants. STUDY DESIGN: Antenatal factors were evaluated in
      302 infants delivered between 24 and 33 completed weeks gestation.
      Ultrasonographic screening of intracranial hemorrhage was carried out in all the
      infants. The association between risk factors and neonatal intracranial
      hemorrhage was evaluated with both univariate and multivariate models. RESULTS:
      In stepwise logistic regression analysis, birthweight was a better predictor of
      neonatal germinal matrix hemorrhage than gestational age. Conversely, gestational
      age better predicted intraventricular hemorrhage than did birthweight. Risk
      factors for neonatal germinal matrix hemorrhage and intraventricular hemorrhage
      were dissimilar. A history of heavy (> 10 cigarettes/day) maternal smoking on
      admission increased the risk of germinal matrix hemorrhage three-fold (odds ratio
      = 3.35; 95% C.I. 1.24-9.07). Antenatal corticosteroid use reduced the risk of
      intraventricular hemorrhage by 76% (odds ratio = 0.24; 95% C.I. 0.09-0.61). Among
      patients with spontaneous preterm delivery or premature rupture of fetal
      membranes, the presence of labor was a significant effect modifier of the
      gestational-age associated risk of germinal matrix hemorrhage-intraventricular
      hemorrhage. CONCLUSIONS: Risk factors for neonatal germinal matrix hemorrhage are
      different from those for intraventricular hemorrhage. Most antenatal factors,
      especially those affecting fetal maturity, could influence the progression rather
      than the onset of intracranial hemorrhage.

PMID- 7635226
TI  - Upper gastrointestinal symptoms in the third trimester of the normal pregnancy.
AB  - OBJECTIVES: To report on the prevalence of well-being, heartburn, nausea, and
      vomiting related to gestational week, parity, and age in the third trimester of
      the normal pregnancy. STUDY DESIGN: Self-administered questionnaire filled in
      daily by 180 women from 31st gestational week to delivery. RESULTS: The study was
      completed by 120 women. The weekly prevalence of well-being decreased from 50% at
      the 31st gestational week to 24% at the 42nd gestational week (P = 0.00001). The
      weekly prevalence of heart-burn (approximately 60%), nausea (approximately 16%)
      and vomiting (approximately 7%) was nearly constant throughout the study period.
      Well-being was inversely related to parity, (P = 0.006), heartburn positively
      related to age (P = 0.016), and nausea and vomiting inversely related to age (P =
      0.003 and P = 0.044). CONCLUSION: Discomforts are customary in the third
      trimester of normal pregnancy. However, heartburn and especially nausea and
      vomiting appeared occasionally and were not present for longer periods. The
      findings that heartburn, nausea and vomiting had different relations to age may
      suggest different etiologies.

PMID- 7635227
TI  - Maternal serum CA 125 levels in first trimester abortion.
AB  - OBJECTIVE: To assess the source of maternal serum CA 125 during the first
      trimester of pregnancy. STUDY DESIGN: CA 125 was measured in stored samples from
      nonviable pregnancies of 8-13 weeks gestation. The study group comprised 19 women
      with vaginal bleeding and 13 non-bleeders. Only patients in whom chromosome
      analysis of the products of conception demonstrated a normal caryotype were
      included. CA 125 levels were expressed in multiples of the median (MoM) for
      normal pregnancies of the same gestational age. RESULTS: Median MoM values of CA
      125 were significantly higher in women with vaginal bleeding (1.81 MoM) as
      compared both to non-bleeders (0.82 MoM; p < 0.01-Mann-Whitney U-test) and to the
      normal pregnancies (1.01 MoM; p < 0.05). No significant difference was found
      between non-bleeding women and controls. CONCLUSIONS: The present study indicates
      that in non-viable pregnancies with euploid fetuses an increase in maternal serum
      CA 125 levels was found only in presence of decidual disruption associated to
      vaginal bleeding. These findings are compatible with a prevalent decidual source
      of this antigen.

PMID- 7635229
TI  - The influence on a 'normal' birthweight distribution of a minor population of
      growth retarded infants: a Monte Carlo simulation.
AB  - It is common practice to define babies below a certain birthweight as 'growth
      retarded' or 'small-for-dates'. This presupposes that there is a specific
      subpopulation of babies who have not achieved their genetic growth potential. The
      presence of this subpopulation should result in a deviation from a normal
      distribution in the population as a whole. We have used a mathematical
      simulation, together with data from an actual sample of 1463 male Caucasian
      neonates delivered at 40 weeks, in order to define the characteristics of such a
      subpopulation which would yield deviations from the normal sufficient to be
      statistically significant. On the basis of this study, there was no evidence for
      such a subpopulation of low birthweight babies in the 1463 neonates observed.

PMID- 7635228
TI  - Prediction of birth weight by ultrasound-estimated fetal weight: a comparison
      between single and repeated estimates.
AB  - OBJECTIVES: Ultrasound estimation of fetal weight is used for diagnosing
      intrauterine growth retardation. The aim of the present study was to assess the
      accuracy of birth weight prediction by use of a single or repeated estimations of
      fetal weight in the third trimester. STUDY DESIGN: 1000 pregnant women considered
      at risk were scheduled to ultrasound estimation of fetal weight, using Warsof's
      formula, at 28, 31, 34 and 37 weeks of gestation. The 421 pregnancies with term
      delivery and complete set of ultrasound examinations and 57 pregnancies with
      preterm delivery with ultrasound examination at 16 and 28 weeks and once more
      before delivery were included in the present analysis. RESULTS: The accuracy of
      birth weight prediction improved significantly for every three weeks from 28 to
      37 weeks of gestation in the term infants. Prediction based on the average of
      repeated weight estimates or linear extrapolation from two estimates or
      extrapolation by a second order polynomium fitted to four estimates did not
      improve accuracy compared to prediction based on the last estimate before
      delivery. CONCLUSION: When more than one ultrasound estimation of fetal weight
      are available, prediction of birth weight in relation to gestational age should
      be based on the last ultrasound examination only.

PMID- 7635230
TI  - Experience with 1251 transcervical chorionic villus samplings performed in the
      first trimester by a single team of operators.
AB  - OBJECTIVE: We report our experience with 1251 chorionic villus samplings (CVS)
      performed by a single team of operators. STUDY DESIGN: From April 1984 through
      August 1993, 1251 CVS were performed in 1236 pregnancies. The transcervical route
      was used in the vast majority and the sampling was performed during the 9th
      through 13th weeks of gestation in 1193 cases (96%). Follow-up was ensured to
      tabulate the pregnancy-related complications and fetal loss rate until 28 weeks'
      gestation. Pregnancy outcome was documented for all but 36 women (3%). RESULTS:
      Most of the tests (72%-891/1236 pregnancies) were performed for advanced maternal
      age (> or = 35 years). The percentage of each indication remained relatively
      stable, around 90% for chromosomal indications and between 8 and 11% for DNA
      studies. Samples adequate for diagnosis were obtained in one or two sessions in
      1179 pregnancies (95%). The rate of spontaneous abortion possibly related to CVS
      was 2.5% (28/1092). Mosaicism confined to the placenta was found in 23 cases
      (1.8%). The pregnancy outcome was known in 1098 pregnancies. There were 10
      perinatal losses (0.9%) and nine congenital malformations (0.8%). No transverse
      limb defects were observed. The rate of premature deliveries (4.6%) and of small
      for gestational age were comparable to the general uninstrumented population.
      CONCLUSION: CVS is a safe and effective mode of antenatal diagnosis when
      performed by a single team of experienced operators.

PMID- 7635231
TI  - Prenatal diagnosis of congenital heart disease; prospects and problems.
AB  - Routine fetal echocardiography has been submitted as an antenatal screening test
      for congenital heart disease despite a wide range of efficacy reported. Hence,
      evaluation of the variable results of prenatal ultrasound screening programs was
      pursued. As the studies appeared to have a heterogeneous design, the originally
      reported figures have been corrected for one plausible prevalence of
      cardiovascular anomalies. Clinical setting (general hospitals vs. teaching
      hospitals), case ascertainment (retrospective vs. prospective; follow-up on
      (suspected) cases only vs. routine follow-up) and length of follow-up (< 1 year
      vs. a longer period) all have similar effects on the reported yield of cases and
      sensitivity of the proposed screening test. Notably, a relatively low yield of
      cases causes a seemingly high sensitivity, whereas a higher yield of cases causes
      a seemingly low sensitivity. Additional factors of study design, e.g. case
      definition, diagnostic procedures and appliances used, were usually not described
      in detail, yet may also have affected the results. Evaluating diagnostic tests
      apparently demands a rigorous study design to overcome biased results.
      Furthermore, no sufficient evidence could be found meriting current routine
      prenatal screening for congenital heart disease.

PMID- 7635232
TI  - Immunogenetic study of couples with recurrent spontaneous abortions.
AB  - OBJECTIVES: Clinical observations suggest that genetic and immunologic disparity
      could be a factor in fecundity. The HLA system (HLA) is polymorphic and TLX
      (Trophoblast Lymphocyte Cross-Reactive), which is also polymorphic, seems to be
      linked to it. The immunologic hypothesis follows that excessive HLA and TLX
      sharing could explain the rejection of a semi-allogenic blastocyst. Study
      objectives are therefore twofold; To determine whether or not there is
      significant HLA-sharing between spouses with unexplained recurrent spontaneous
      abortions (RSA) and to determine whether or not there is an association between
      some HLA specificities and RSA. STUDY DESIGN: The study includes only Caucasian
      couples that have had three successive spontaneous abortions. These were
      distributed in two groups: Group E: 18 couples either with known aetiology or
      with secondary RSA; Group U: seven couples with unexplained primary RSA; Control
      group C: 21 couples with at least two children and no spontaneous abortions.
      Tissue typing for HLA-A and B molecules was performed using serotyping
      methodology based on lymphocytotoxicity reaction. The different DRB1 alleles
      (class II) were determined by oligotyping with a non-radioactive reverse dot-blot
      methodology. RESULTS: Statistical comparison shows that the number of couples
      without shared specificity is not significantly different between the three
      groups for each locus independently and for the set of three. Our results show
      also that the allelic frequencies are not significantly different between the
      three groups. CONCLUSIONS: There is no higher HLA-sharing in couples with RSA
      than in fertile couples. Similarly, no particular HLA specificity can be
      associated with the RSA.

PMID- 7635233
TI  - Tumor status of lymph nodes in early endometrial cancer in relation to lymph node
      size.
AB  - A retrospective analysis of 36 patients with metastatic nodes out of 209
      consecutively managed patients with a clinically stage I endometrial cancer was
      carried out. Of the 1023 lymph nodes removed, 154 nodes were found to be
      metastatic. The mean number of the involved nodes was 4.27 (range: 1-29). Of the
      154 positive nodes, 3 had nodal diameters < or = 3 mm (1.9%), 84 had diameters of
      4-10 mm (54.6%), 60 had diameters of 11-20 mm (39.0%) and 7 had diameters more
      than 20 mm (4.5%). With increasing lymph node size, the frequency of tumoral
      involvement varies from 1.0% in nodes < or = 3 mm to 63.6% in nodes bigger than
      20 mm. In terms of patients, nine of them were found to have a single metastatic
      node ranging from 6 mm to 10 mm in diameter. In the remaining 27 patients with
      multiple metastatic nodes, the biggest nodes encountered were 6-10 mm in 4
      (14.8%), 11-20 mm in 17 (62.9%) and more than 20 mm in 6 (22.2%) patients. Since
      mere sampling of the lymphatic tissue directed particularly to the enlarged nodes
      may not show the true incidence of positive nodes, a complete lymphadenectomy is
      advocated in order to obviate an understaging problem.

PMID- 7635234
TI  - Interleukin-6 in amniotic fluid obtained at forewater amniotomy compared with
      hindwater samples in women in spontaneous labour.
AB  - Using an aseptic technique, samples of amniotic fluid were obtained from the
      forewaters and hindwaters of fifteen women in spontaneous labour with a deeply
      engaged fetal head. Prior to sampling, a cervical swab was obtained to exclude
      infection and in 10 cases samples of amniotic fluid were sent for microscopy and
      culture. Forewater samples were obtained using a pudendal block needle. Hindwater
      samples were obtained after membrane rupture by inserting an intra-uterine
      pressure catheter. Batch assay for interleukin-6 (IL-6) concentrations was
      performed using a specific ELISA. The levels of IL-6 in forewater samples of
      amniotic fluid were significantly higher than those found in hindwater samples (t
      = 3.65, P < 0.002). This suggests that either the production of IL-6 as a result
      of stimulation by its cytokine 'effectors' is greater at this site, or that the
      loss or metabolism of IL-6 in the forewaters is less than that in the hindwaters.
      The concentration of IL-6 parallels the reported levels of PGE2, and it is
      therefore likely that if IL-6 is involved in the mechanism of labour it acts
      through the effects of the resultant PGE2 release.

PMID- 7635235
TI  - Realization of estradiol effects in the uterus of ovariectomized rats under acute
      stress.
AB  - The aim of this study was to examine the influence of acute stress on the
      realization of the effects of estrogens in the uterus of ovariectomized rats. The
      rats were immobilized for 6 h and given a single injection of estradiol
      dipropionate (E2; 10 micrograms/rat, i.m.). E2-only treated rats, olive oil
      injected and stressed rats, olive oil-only treated rats and untreated
      ovariectomized animals were used as controls. The effect of E2 was assessed by
      the volumes of cells, nuclei and nucleouli (morphometry), DNA content (Feulgen
      technique) and proliferative activity (mitotic index) in luminal epithelium, in
      glandular epithelium and in stromal cells of endometrium 24, 36 and 48 h after
      the injection of E2 or olive oil. All the effects of E2 were reduced in E2
      treated rats subjected to stress in all the uterine structures. In olive oil
      treated rats, stress induced certain increase in the volume of cells and nuclei
      and slight increase in the DNA content in all the structures. It is suggested
      that the influence of stress on the uterus is mediated by impairment of some
      septs in the mechanism of action of estrogen on the uterus, which leads to a
      decrease in the sensitivity of the uterine structures to estrogens. Without
      estrogen stimulation the effect of stress on the uterus is realized via estrogen
      independent pathways.

PMID- 7635236
TI  - The effect of interleukin-1 in rabbit cervical ripening.
AB  - OBJECTIVE: In this research we studied the effect of interleukin-1 beta (IL-1
      beta) on the cervix. STUDY DESIGN: Vaginal suppositories of a low dose of IL-1
      beta (200 ng) were applied to non-pregnant and pregnant rabbits. Results were
      compared with a control group which were treated only by placebo. Water
      concentration, collagen content, collagenase and elastase activities were
      measured. Neutrophil numbers in the cervical connective tissue were counted.
      Also, interleukin-8 (IL-8) was measured in the supernatant of homogenized
      cervical tissue treated by IL-1 beta. RESULTS: Water contents of the tested
      cervices were increased (P < 0.006 and 0.03, respectively), whereas collagen
      content was markedly decreased (P < 0.0004 and 0.001, respectively). Collagenase
      activity was found to be increased in non-pregnant and pregnant cervices treated
      by IL-1 beta (P < 0.02 and 0.002, respectively). Also, elastase activity of these
      cervices were significantly increased compared to the control group (P < 0.0007
      and 0.001, respectively). Neutrophil invasion was observed in the cervical
      connective tissues after application of IL-1 beta. IL-8 was significantly
      elevated (P < 0.0001) in the treated cervices. CONCLUSION: Interaction between IL
      1 and IL-8 is suspected to be essential for cervical ripening.

PMID- 7635237
TI  - Successful pregnancy in a patient with Churg-Strauss syndrome.
AB  - Vasculitis syndromes rarely occur in association with pregnancy and usually have
      a poor prognosis. We report the case of a 32-year-old woman, affected by Churg
      Strauss syndrome in complete remission at the time of conception, who completed a
      successful pregnancy. The patient did well except for a recurrence of allergic
      rhinitis and asthma which apparently responded to an increase in steroid dosage.
      Clinical implications of vasculitis and pregnancy are discussed.

PMID- 7635239
TI  - Angiosarcoma of the breast and pregnancy: a new therapeutic approach.
AB  - A case of angiosarcoma of the breast managed primarily by a chemotherapeutic
      approach is referred. A 29-year-old patient presented complaining of a painful
      mass in her right breast. An incisional biopsy carried out under general
      anesthesia showed a moderately-differentiated angiosarcoma surrounded by
      fibrofatty tissue. Ruled out distant metastases, a decision was made to initiate
      neoadjuvant chemotherapy consisting of ifosfamide, vincristine and dactinimycin.
      After 2 courses of chemotherapy the tumor volume was reduced by 50% and the
      histologic examination of the mastectomy specimen revealed a well-differentiated
      angiosarcoma with widespread areas of necrosis probably produced by previous
      chemotherapic treatment. The patient is clinically free of disease after 24
      months of follow-up. Although this is a single case report, and by no means can
      be considered a guideline for future treatments, we nevertheless feel that the
      result obtained with the chemotherapeutic approach with this patient is
      encouraging.

PMID- 7635240
TI  - Retinal detachment in association with preeclampsia and abruptio placentae.
AB  - Retinal detachment is a rare complication of preeclampsia, eclampsia and abruptio
      placentae. We report a case of bilateral retinal detachment in association with
      severe preeclampsia complicated with abruptio placentae, intrauterine fetal death
      and disseminated intravascular coagulation. In obstetric complications, placental
      thromboplastin may release into maternal circulation and activate the extrinsic
      coagulation system with resultant disseminated intravascular coagulation. This
      may be responsible for choroidal ischemia and consequent serous retinal
      detachment.

PMID- 7635238
TI  - Prolonged intake of chlorambucil for ovarian cancer.
AB  - The use of alkylating agents has been reported to be a cause of secondary
      leukemia particularly in patients surviving for 2 years or more after treatment
      of ovarian carcinoma. The risk of developing leukemia is possibly related to the
      duration of treatment and the total dose of alkylating agents administered. We
      report a patient with epithelial ovarian carcinoma who received chlorambucil for
      130 consecutive months with no clinical or laboratory evidence of leukemia.

PMID- 7635241
TI  - Prejunctional actions of muscle relaxants: synaptic vesicles and transmitter
      mobilization as sites of action.
AB  - 1. Nicotinic antagonists such as tubocurarine affect acetylcholine release from
      motor nerve terminals at the neuromuscular junction. 2. Electrophysiological
      studies comparing the prejunctional actions of tubocurarine to those of vesamicol
      and vecuronium have been used to provide an insight into the mechanisms involved
      in the prejunctional effects of tubocurarine-like compounds. 3. The observed
      prejunctional actions of tubocurarine can be accounted for by a model in which
      the compound has two separately identifiable effects on the nerve terminal. At
      low frequencies of nerve stimulation tubocurarine augments acetylcholine release
      while at high frequencies of nerve stimulation tubocurarine depresses
      acetylcholine release. 4. Both of the effects of tubocurarine on acetylcholine
      release are a consequence of a change in the number of quanta within the nerve
      terminal immediately available for release upon nerve stimulation. 5. On the
      basis of our experimental observations, we suggest that the two prejunctional
      effects of tubocurarine are mediated through two pharmacologically distinct
      prejunctional nAChRs.

PMID- 7635242
TI  - Excess EDRF/NO, a potentially deleterious condition that may be involved in
      accelerated atherogenesis and other chronic disease states.
AB  - 1. To date, no method exists for preventing the injury-induced, accelerated
      atherogenesis that can occur as a "late complication" after initially successful
      invasive cardiovascular therapy (e.g. coronary angioplasty, endarterectomy). The
      problems intrinsic to some of the therapeutic approaches that are presently being
      developed have been analyzed, and the need for an alternative approach is
      evident. 2. An hypothesis is advanced, providing a novel conceptual basis for
      developing preventive therapy for accelerated atherogenesis, as well as for other
      chronic (degenerative) disease states, using agents that selectively inhibit the
      actions and metabolic transformations of excessive amounts of endogenously
      derived and/or exogenously-acquired nitric oxide (NO). 3. It is considered that
      excess NO can damage tissue by enhancing the formation of hydroxyl radicals (OH.)
      via the peroxynitrite pathway and alpha-hydroxynitrosamines via nitrosation
      processes, and that it can stimulate cell proliferation by activating guanyl
      cyclase. These actions would facilitate the process of accelerated atherogenesis.
      4. Selectivity for opposing the effects and metabolic handling of excess NO,
      regardless of its origin (endogenous via the action of constitutive or inducible
      NO synthase, or exogenous), rather than selectivity for inhibiting the activity
      of inducible versus constitutive NO synthase, is considered to be the key element
      required of candidate therapeutic agents. 5. The vitamin C derivative, 2-O
      octadecylascorbic acid, which could protect that part of the NO mechanism that is
      essential for normal function by scavenging superoxide anion-radicals (O2-.,
      while preventing the formation of OH. and potentially toxic nitrosamines via
      metabolic reactions involving excess NO, represents a model compound for
      developing effective therapy.

PMID- 7635243
TI  - Aromatic L-amino acid decarboxylase: biological characterization and functional
      role.
AB  - 1. Aromatic L-amino acid decarboxylase is the enzyme responsible for the
      decarboxylation step in both the catecholamine and the indolamine synthetic
      pathways. Immunological and molecular biological studies suggest that it is a
      single enzyme with one catalytic site but with different locations for attachment
      of the substrates. The enzyme is widely distributed in the brain and in
      peripheral tissues. 2. Recent investigations have shown that the enzyme is
      regulated by short term mechanisms that may involve activation of adenyl cyclase
      or protein kinase C. In addition, a long-term mechanism of activation by altered
      gene expression has also been suggested.

PMID- 7635244
TI  - Heparin: pharmacological potentials from atherosclerosis to asthma.
AB  - 1. Heparin belongs to a family of polysaccharide species, whose best known
      property is, undoubtedly, anticoagulant activity. However, heparin has many other
      pharmacological effects, particularly on the cardiovascular system. 2. The
      therapeutic use of chronically inhaled heparin has been suggested as prophylaxis
      in atherosclerosis. 3. Heparin, physiologically stored in mast cells of the
      respiratory system, has also been recently studied in the prevention of
      immunological and non-immunological asthmatic attacks. 4. Experimental findings
      and new hypotheses of heparin action in asthma and atherosclerosis are discussed.

PMID- 7635245
TI  - Pharmacological properties of MM-706, a new prostacyclin derivative.
AB  - 1. In human platelet-rich plasma, platelet aggregation induced in vitro by
      collagen (10 micrograms/ml) or thrombin (50 mU/ml) was dose-dependently inhibited
      by increasing concentrations of prostacyclin or of the new derivative (+/-)(5E)
      13,14-didehydro-omega-hexanor(1-hydroxycyclo hexyl)-9a- carbaprostacyclin (MM
      706) with an IC50 of 20-50 nM and 250-500 nM, respectively. In human platelets
      loaded with fura-2, the intracellular rise of [Ca2+] induced by thrombin was dose
      dependently inhibited by MM-706 with an approximate IC50 of 100 microM. 2. In
      rabbit isolated femoral artery, MM-706 (10 nM-10 microM) was completely
      ineffective in relaxing the vessel, which was different to prostacyclin which was
      able to relax vessels at the same concentrations. 3. In in vitro guinea-pig
      ileum, prostacyclin produced a contractile effect in the concentration range 1 nM
      10 microM, but the derivative MM-706 was ineffective at the same concentrations.
      Preventive addition of MM-706 did not inhibit prostacyclin contraction. 4. On
      isolated guinea-pig tracheal preparation, prostacyclin induced a concentration
      dependent contraction but the new compound MM-706 showed a lower activity, in the
      concentration range 10 nM-10 microM. The activity of prostacyclin was not
      affected by the contemporary presence of MM-706. 5. It is concluded that MM-706
      is a prostacyclin analogue with antiaggregating properties but without evident
      effects on smooth muscle of different regions.

PMID- 7635246
TI  - Antidiuretic hormone decreases the intracellular pH in distal nephron epithelium
      (A6) by inhibiting Na+/H+ exchange.
AB  - 1. To clarify the effect of arginine vasotocin (AVT) on intracellular pH (pHi) of
      A6 cells (an amphibian renal cell line), we measured pHi with a single-cell
      fluorescent imaging system in an HCO3(-)-nominally-free medium. 2. AVT (40 mU/ml)
      significantly decreased pHi from 7.44 +/- 0.11 to 7.19 +/- 0.22 (mean +/- SE) by
      inhibiting the Na+/H+ exchanger. 3. A membrane-permeable analogue of cAMP,
      dibutyryl cAMP (1 mM), significantly decreased pHi from 7.40 +/- 0.02 to 7.17 +/-
      0.02, a response similar to that of AVT. 4. These data indicate that, in A6
      cells, AVT suppresses the Na+/H+ exchanger via a cAMP-dependent pathway and the
      Na+/H+ exchanger maintains pHi under HCO3(-)-nominally-free conditions.

PMID- 7635247
TI  - Chronic manipulation of dietary salt modulates renal physiology and kidney
      dopamine receptor subtypes: functional and autoradiographic studies.
AB  - 1. Compared to rats maintained on the normal NaCl (0.33%) diet, animals
      maintained on the low NaCl (0%) diet for 4 weeks exhibited increased plasma
      aldosterone and chloride and decreased urinary sodium excretion. 2. Rats
      maintained on the high NaCl (8%) diet for 4 weeks showed increased systolic blood
      pressure, water intake, urine volume, sodium and dopamine excretion and decreased
      plasma aldosterone and glomerular filtration rate. 3. Administration of SCH 23390
      (10 mg/kg, po), but not domperidone to the high salt diet rats attenuated the
      diuretic effect, indicating the involvement of DA1 rather than DA2 receptors. The
      dopamine decarboxylase inhibitor, carbidopa (30 mg/kg, i.p.), also reduced the
      high salt-induced diuresis. 4. Kidney sections from rats fed the low NaCl diet
      showed a 63-100% decrease (P < 0.001-0.02) in cortical and medullary DA1 and DA2
      binding sites, while rats fed the high NaCl diet demonstrated only a 70% decrease
      (P < 0.01-0.02) in cortical DA1 binding, without affecting DA2 binding. 5. These
      data indicate that chronic modification of dietary salt profoundly affects the
      sodium, water and dopamine excretion and leads to selective modulation of renal
      dopamine receptor subtypes.

PMID- 7635248
TI  - Effects of acetylsalicylic acid on serotonin brain receptor subtypes.
AB  - 1. The lysine salt of acetyl salicylic acid (ASA) at a dose equivalent to 400
      mg/kg of acetyl salicylic acid (ASA) was intraperitoneally administered in rats.
      2. After 30 and 120 min ASA did not modify the number of receptors nor the
      affinity of [3H] 8-OH-DPAT binding sites in pons and cerebral cortex. On the
      other hand, the receptor number in the cortex membranes decreased significantly
      using [3H] ketanserin as ligand, while the receptor number in the pontine
      membranes did not change. 3. These data support the involvement of central 5-HT
      receptors in the mode of action of ASA.

PMID- 7635249
TI  - Alpha-1 and beta-adrenergic receptor blocking potencies of bopindolol and its two
      metabolites (18-502 and 20-785) as assessed by radioligand binding assay methods.
AB  - 1. The pKi value of bopindolol for alpha 1High-subtypes in canine aorta, rat
      hearts and rat brain was 5.71, 5.52 and 6.56, respectively. In addition, the pKi
      values of these drugs in canine aorta, rat hearts and rat brain for the alpha
      1Low-subtype was very low. 2. The phenylephrine induced-contractions of aortae of
      guinea pigs and rats were not inhibited by these agents. 3. Both bovine hearts
      and tracheal smooth muscles indicated that 18-502 had the highest pKi value to
      beta 1- and beta 2-adrenoceptor subtypes and the rank order of these beta
      blocking potencies were 18-502 > bopindolol > 20-785.

PMID- 7635250
TI  - Enhancement in gastric mucosal EGF and PDGF receptor expression with ulcer
      healing by sulglycotide.
AB  - 1. The effect of an antiulcer agent, sulglycotide, on mucosal expression of EGF
      and PDGF receptors with chronic ulcer healing was investigated. 2. Rats with
      experimentally-induced gastric ulcers were treated twice daily for 14 consecutive
      days, either with sulglycotide at 200 mg/kg or vehicle, and at different stages
      of treatment used for quantitation of gastric mucosal EGF and PDGF receptors. 3.
      The ulcer healing was accompanied by an increase in mucosal expression of both
      types of receptors. A 1.8-fold increase in EGF and 3.1-fold increase in PDGF
      receptors occurred by the 4th day following the development of ulcer and reached
      a maximum of 2.4-3.9-fold increase by the 10-14th day. 4. Treatment with
      sulglycotide caused accelerated ulcer healing accompanied by a significant
      enhancement in the receptors expression. A 2.3- and 3.6-fold increase in EGF and
      PDGF receptor expression occurred by the 4th day of sulglycotide treatment,
      reaching a 5.5- and 5.6-fold respective increase by the 10th day when the ulcer
      essentially healed. 5. The results attest to the ability of sulglycotide to
      stimulate the gastric mucosal proliferative activities associated with ulcer
      healing.

PMID- 7635251
TI  - Complex avoidance behaviour and its neurochemical regulation in the land snail
      Cepaea nemoralis.
AB  - 1. In hot plate experiments, the pulmonate land snail Cepaea nemoralis displays a
      biphasic passive/active avoidance behaviour composed of retraction and subsequent
      searching mediated by antagonistic muscular systems. The switch, between the
      behaviours, is under neuronal control. 2. Leu- and met-enkephalin, as well as
      FMRFamide-antiserum, attenuated the retraction response and potentiated the
      searching behaviour. Opposite effects were achieved by injection of antisera to
      the enkephalins. 3. Both retraction and searching behaviours were potentiated by
      5-HT. Methysergide antagonized the effects of the enkephalins on the searching
      behaviour. 4. We conclude that endogenous opioids act antagonistic to FMRFamide
      in the neuronally controlled switch between passive and active avoidance
      behaviour.

PMID- 7635252
TI  - Evidence for serotonergic system involvement in the effect of morphine on
      gastrointestinal motility in the rat.
AB  - 1. Intestinal motility was measured by the transit of charcoal meal through the
      small intestine of the rat. 2. Morphine given subcutaneously induced a reduction
      in the gastrointestinal transit (GIT), and the response was dose-dependent (0.1
      2.5 mg/kg). 3. The inhibitory effect of morphine was antagonized by prior
      subcutaneous administration of naloxone (1 mg/kg). 4. Depletion of serotonergic
      neurons by para-chlorophenylalanine (100 mg/kg, ip, 3 days) completely abolished
      the inhibitory action of morphine. 5. Methysergide (5 mg/kg, sc) and ketanserin
      (5 mg/kg, sc) also reduced the morphine effect. 6. Destruction of serotonergic
      neurones by intracerebroventricular injection of 5,7-dihydroxytryptamine (20
      mu/kg) abolished the effect of morphine. 7. These observations provide some
      evidence for the involvement of a central serotonergic system in the effect of
      morphine on gastrointestinal motility.

PMID- 7635253
TI  - Potentiation of the hypoxic contraction of guinea-pig isolated pulmonary arteries
      by two inhibitors of superoxide dismutase.
AB  - 1. Isolated proximal and distal extralobar branches of the pulmonary artery of
      the guinea-pig develop slow and well-sustained contractions in response to
      hypoxia (PO2 11-15 mm Hg) without prior stimulation with an agonist. These
      contractions are readily reversible by readministration of oxygen. 2. Incubation
      of these preparations with diethyldithiocarbamic acid (DETCA, 5 mM for 30 min),
      an inhibitor of superoxide dismutase, significantly increased the hypoxic
      contractions whether DETCA was added before the challenge with hypoxia or after
      the hypoxic contraction had reached a plateau. This treatment also reduced the
      oxygen-induced relaxation. 3. Similarly, incubation with triethylenetetramine
      (TETA, 5 mM for 30 min), another inhibitor of superoxide dismutase, produced
      larger potentiation of the hypoxic contraction in the two preparations and
      reduced the oxygen-induced relaxation. 4. Furthermore, addition of H2O2 (10(-5) M
      3 x 10(-4) M) caused concentration-dependent relaxation of the hypoxic
      contraction while larger concentrations (10(-3) M and 3 x 10(-3) M) caused
      contraction that did not respond to readministration of oxygen. 5. These
      observations suggest that during hypoxic stress, the accumulation of superoxide
      anions may participate in the hypoxia-induced contraction and that the metabolism
      of these radicals into H2O2 by superoxide dismutase maintains the relaxed state
      during normoxia.

PMID- 7635254
TI  - Electrophysiological effects of tiracizin and its metabolites in dog cardiac
      Purkinje fibers.
AB  - 1. Conventional microelectrode technique was used to study the effects of
      tiracizin and its two main metabolites on the action potential parameters in dog
      cardiac Purkinje fibers. 2. Tiracizin induced a use-dependent depression of the
      maximal rate of depolarization during the upstroke of the action potential (EC50
      = 0.323 +/- 0.059 microM, n = 5) and decreased the action potential duration
      (EC50 = 0.230 +/- 0.024 microM, n = 5). 3. The two main metabolites exerted
      similar effects, but only at concentrations about one order of magnitude higher
      than tiracizin. 4. It was concluded that the electrophysiological effects of
      tiracizin in dog Purkinje fibers correspond to those of Class I antiarrhythmic
      drugs also in cardiac Purkinje fibers. The main metabolites are less potent than
      the parent compound, therefore it is likely that their effects play a less
      important role in the beneficial effect of tiracizin in cardiac arrhythmias.

PMID- 7635255
TI  - Dalargin and [Cys-(O2NH2)]2 analogues of enkephalins and their selectivity for mu
      opioid receptors.
AB  - 1. Effects of the enkephalins Met-enk (M) and Leu-enk (L), of two newly
      synthesized analogues--[Cys-(O2NH2)]2-Met-enk (CM) and [Cys-(O2NH2)]2-Leu-enk
      (CL)--and of a hexapeptide--D-Ala2-Leu5-Arg6 (Dalargin; DL) on the spontaneous
      and electrically stimulated activity were examined with respect to their
      selectivity for the mu opioid receptors in the longitudinal layer of guinea pig
      ileum. 2. M and CM exerted relaxing and contractile effects on the spontaneous
      contractile activity while L, CL and DL produced only relaxation. The order of
      potency towards the relaxatory phase was DL > M > CM > L > CL and towards the
      contractile phase CM > M. 3. The effects of enkephalins on the spontaneous
      activity were naloxone and TTX sensitive except for the contractile phase of M
      and CM which persisted in the presence of TTX. NO was not involved in the
      neurotransmission of the relaxatory responses, while the blockade of alpha and
      beta adrenoceptors showed the participation of adrenergic mechanisms. Relaxation
      and contraction induced by enkephalins could not be directly attributed to
      cholinergic neurotransmission. 4. The naloxone-sensitive and concentration
      dependent inhibitory effects of enkephalins and their analogues on the
      electrically stimulated cholinergic contractions were established. The order of
      the relative potency of opioids was: DL-3.8; M-1.0; L-0.4; CM-0.01; CL-0.005. 5.
      These data indicated that the D-Ala2 substitution and lengthening of the peptide
      chain by Arg6 in the molecule of L increased the potency at the mu opiate
      receptors, while the substitution in position 2 with Cys-(O2NH2) in the molecule
      of M and L yielded a less potent and selective mu agonists.

PMID- 7635256
TI  - Effect of piroxicam beta-cyclodextrin complex on experimental inflammation.
AB  - 1. The effectiveness of the inclusion product of piroxicam with beta-cyclodextrin
      was compared to that of free piroxicam on inflammatory reactions by using three
      experimental inflammatory models in rats. 2. The inclusion compound showed anti
      inflammatory effects similar to those of simple piroxicam on granuloma tissue
      formation and arthritis induced by complete Freund adjuvant. 3. In carrageenin
      induced pleurisy, the piroxicam beta-cyclodextrin reduced leukocyte mobilization
      more intensely than non-complexed piroxicam. 4. These results suggest that beta
      cyclodextrin is a useful tool for improving the efficacy of piroxicam.

PMID- 7635257
TI  - The activity of flavonoids extracted from Tanacetum microphyllum DC. (Compositae)
      on soybean lipoxygenase and prostaglandin synthetase.
AB  - 1. The in vitro effects of centaureidin and 5,3'-dihydroxy-4'-methoxy-7
      carbomethoxyflavonol (Fig. 1), two anti-inflammatory flavonoids extracted from
      Tanacetum microphyllum DC., have been examined on both cyclooxygenase and
      lipoxygenase activity. 2. These flavonoids produced an inhibition of soybean
      lipoxygenase activity in a dose-dependent manner, with IC50 values (20 and 29
      microM respectively) similar to the reference drug. 3. The IC50 values for the in
      vitro inhibition of cyclooxygenase activity by these flavonoids, were higher than
      those that produced lipoxygenase activity (318 and 60 microM respectively). 4.
      These results suggest that the anti-inflammatory activity of our flavonoids may,
      at least in part, be due to the inhibition of leukotriene synthesis. 5. This is
      the first report of the biological activity in vitro of these compounds.

PMID- 7635258
TI  - Involvement of alpha 2-adrenoceptors and protein kinase C on nicotine-induced
      facilitation of noradrenaline release in bovine cerebral arteries.
AB  - 1. Incubation of bovine cerebral vessels (previously exposed to [3H]
      noradrenaline) with nicotine for 30 sec produced a facilitation of the
      electrically-induced noradrenaline release, which was antagonized by
      hexamethonium, a blocker of nicotinic receptors. This facilitation was not
      observed when the incubation time was increased to 20 or 75 min. 2. Rauwolscine,
      an alpha 2-adrenoceptor blocker, enhanced and phorbol 12, 13-dibutyrate reduced
      the facilitator effect produced by 30 sec exposure to nicotine. 3. These data
      suggest: (1) presynaptic nicotinic receptors produce a facilitation of stimulated
      noradrenaline release; these receptors are easily desensitized by increasing the
      incubation time with nicotine; (2) protein kinase C and alpha 2-adrenoceptors
      appear to be involved in this process.

PMID- 7635259
TI  - Cholinergic dependence of pancreatic response to cholecystokinin in rats and
      guinea pigs.
AB  - 1. Lorglumide and atropine were used to examine the role of cholinergic
      mechanisms in the pancreatic secretory response to cholecystokinin in two animal
      species. 2. Anaesthetized rats and guinea pigs with jugular vein and pancreatic
      cannulae were used and the bile juice was recirculated. In the rat, the treatment
      with lorglumide (3 mumol/kg) as well as atropine (100 micrograms/kg) did not have
      effects on basal interdigestive secretion, whereas in guinea pigs only atropine
      decreased the protein output (41%) and the juice flow (47%) of the basal
      pancreatic secretion. 3. Infusion of cholecystokinin (150 pmol/kg/hr in the rat
      and 50 pmol/kg/hr in the guinea pig) induced a marked increase in pancreatic
      juice flow and protein output compared to saline controls. Pretreatment of both
      rat and guinea pig with lorglumide resulted in a marked attenuation of the
      cholecystokinin-evoked secretory response. 4. In the rats, atropine decreased the
      response to infusion of cholecystokinin octapeptide while this antimuscarinic
      agent had no effect in the response to cholecystokinin in the guinea pigs. 5.
      This study supports the concept that the influence of cholinergic system in
      pancreatic response to cholecystokinin shows interspecific differences.

PMID- 7635260
TI  - Effects of lithium on rat parotid and submandibulary gland functions.
AB  - 1. Pure submandibular and parotid saliva were collected intraorally by micro
      polyethylene canula from anesthetized lithium treated and control rats using
      pilocarpine as secretagogue. 2. Acute intraperitoneal injection of a single dose
      of lithium chloride (10 mg/kg), caused a significant decrease in protein,
      calcium, potassium and sodium concentrations of parotid saliva and also a
      significant decrease in protein, potassium and calcium concentrations of
      submandibular saliva. 3. Chronic treatment of rats for 10 days by LiCl solution
      (1200 mg/l) also caused some marked changes in saliva compositions similar to
      those observed in acute experiment. 4. The results of this study suggest that
      lithium as a drug used in the treatment of affective disorders can influence the
      secretory mechanisms of both submandibular and parotid glands. 5. These effects
      of lithium in composition of parotid and submandibular saliva are not related to
      duration of treatment.

PMID- 7635264
TI  - Steroid nomenclature.

PMID- 7635263
TI  - Henderson-Hasselbalch equation is inadequate for the measurement of transmembrane
      diffusion of drugs and buccal drug absorption is a useful alternative.
AB  - 1. The transmembrane diffusion of weakly acidic or basic drugs is being commonly
      assessed from their degree of ionization or ratio unionized/ionized forms (ratio
      U/I) as calculated from Henderson-Hasselbalch equation (HHEq). 2. Buccal drug
      absorption (BA) at pH 5-9 has been proposed as an in vivo model for passage of
      drugs across lipid membranes. 3. Area under the curve (AUC) of BA against pH 5-9
      of 18 basic drugs has been reported to be significantly related to their pH
      dependent renal excretion. 4. We have calculated, using HHEq, ratios U/I of 10
      weak bases at pH 5-9 and 10 weak acids at pH 4-8, whose percentage BA at these pH
      levels was available in the literature. 5. These ratios were not related to their
      %BA at corresponding pH levels. 6. Therefore it is proposed that HHEq is
      inadequate in the anticipation of transmembrane diffusion of drugs and AUC of %BA
      of drugs at pH 4-9 is a useful alternative.

PMID- 7635262
TI  - Adenosine selectively depresses muscarinic compared with non-muscarinic receptor
      mediated depolarisation of the rat superior cervical ganglion.
AB  - 1. A grease gap d.c. recording technique was used to measure electrophysiological
      responses of the isolated rat superior cervical ganglion. 2. Adenosine at 100
      microM depressed depolarisations to the muscarinic agonists carbachol, muscarine
      and methylfurmethide. In contrast adenosine (100 microM) did not alter
      depolarisations to 1,1-dimethyl-4-phenylpiperazinium, 2-methyl-5
      hydroxytryptamine and potassium and enhanced depolarisations to 5
      hydroxytryptamine and gamma-aminobutyric acid. 3. Adenosine-induced depressions
      of the depolarisations to carbachol, muscarine, and methylfurmethide tended to be
      increased in the presence of 0.3 microM methoctramine (a muscarinic receptor
      antagonist with slight selectivity for M2 receptors). The increase was
      statistically significant (P < 0.01) for carbachol. 4. Medium containing 0.1 mM
      Ca2+ and 0.3 microM pirenzepine augmented the hyperpolarising phase of the
      response to carbachol. Adenosine (10-300 microM) hyperpolarised ganglia and did
      not significantly alter the hyperpolarisation to 0.3 or 1 microM carbachol but
      selectively reduced the depolarisation response to 3 microM carbachol. 5.
      Adenosine-induced hyperpolarisations (100 microM) were enhanced when applied
      during depolarisations to muscarinic agonists (muscarine, pilocarpine, N-methyl-N
      (l-methyl-4-pyrrolidine-2-butynyl)acetamide (BM-5)), and other M-current
      inhibitors, barium and eledoisin-related-peptide. Adenosine induced
      hyperpolarisations were not affected by D-Ala6-luteinizing-hormone-releasing
      hormone or uridine 5'-triphosphate which produced small depolarisations. 6. It is
      concluded that adenosine acts selectively in opposing mechanisms of
      depolarisation of the rat SCG that are due to the action of muscarinic agonists
      (acting via M1-receptors) and by other M-current inhibitors.

PMID- 7635261
TI  - Potentiation by endothelin-1 of Ca2+ sensitivity of contractile elements depends
      on Ca2+ influx through L-type Ca2+ channels in the canine cerebral artery.
AB  - 1. Endothelin-1 (ET-1) contracted canine cerebral artery in a concentration
      dependent manner with an increase in intracellular Ca2+ concentration ([Ca2+]i),
      and at higher concentrations it produced a greater contraction with a smaller
      increase in [Ca2+]i. 2. Ca2+ channel antagonist such as d-cis-diltiazem inhibited
      the tension more effectively than the [Ca2+]i increased by ET-1. 3. In Ca(2+)
      free solution containing 0.2 mM EGTA, ET-1 elicited a transient increase in
      [Ca2+]i and tension. 4. In the Staphylococcus aureus alpha-toxin-permeabilized
      artery, ET-1 shifted the pCa-tension relationship leftwards in the presence of
      GTP. 5. These findings suggest that ET-1 contracts the canine cerebral artery by
      increasing not only the Ca2+ influx through L-type Ca2+ channels, but also Ca2+
      release from the intracellular storage sites, and also Ca2+ sensitivity of
      contractile elements. The degree of Ca2+ sensitivity is strongly affected by
      [Ca2+]i which is increased by the Ca2+ influx through L-type Ca2+ channels.

PMID- 7635265
TI  - An in vitro model suitable for studying insulin secretion in amphibians.
AB  - The aim of this work was to develop an in vitro model suitable for studying
      insulin secretion in amphibians and for identifying agents capable of either
      blocking or stimulating such a process in this group. For this purpose,
      pancreases from the toad Bufo arenarum were incubated for 60 min at 25 degrees
      with several insulin secretagogues and blockers, and the immunoreactive insulin
      released into the medium was measured by radioimmunoassay. Under these
      experimental conditions, metabolic (glucose, ketoisocaproic acid, and arginine)
      and nonmetabolic (K+ and tolbutamide) agents as well as glucagon and
      acetylcholine significantly stimulated the release of immunoreactive insulin.
      Conversely, somatostatin and nifedipine blocked its secretion. All these agents
      exerted similar effects on the mammalian pancreas. These results prove that our
      model is a useful tool with which to study in vitro insulin secretion in
      amphibians and to identify agents which affect hormone release in this group.

PMID- 7635266
TI  - Diurnal variations of serum and testicular testosterone and dihydrotestosterone
      (DHT) in Djungarian hamsters (Phodopus sungorus): testes are the main source for
      circulating DHT.
AB  - Testes and sera of adult Djungarian hamsters kept in a light:dark cycle of 16L:8D
      were collected every 1.5-3 hr for 24 hr. The concentrations of testosterone (T)
      and its metabolite 5 alpha-dihydrotestosterone (DHT) were estimated by HPLC
      separation of the steroids followed by radioimmunoassay. Both testicular and
      serum concentrations of T and DHT exhibited strong diurnal variations (P < 0.001)
      with highest levels at the end of the light phase, while both hormones declined
      drastically during the dark period. The ratios of DHT/T, as an indicator of the
      activity of the enzyme 5 alpha-reductase, were on average 0.39 in the testes and
      0.29 in serum. Comparisons of individual data revealed highly significant
      correlations between testicular and serum concentrations of the hormones (T:r =
      0.87; P < 0.0001; DHT:r = 0.69, P < 0.0001). Likewise, the individual values of
      testicular and serum DHT/T ratios correlated highly significantly (r = 0.60; P <
      0.001). The results indicate that in Djungarian hamsters the main source of DHT
      is the testes, while the peripheral conversion of T to DHT seems to be
      negligible.

PMID- 7635267
TI  - Effects of feeding, fasting, background adaptation, acute stress, and exhaustive
      exercise on the plasma somatolactin concentrations in rainbow trout.
AB  - Plasma somatolactin (SL) concentrations in rainbow trout were examined under
      various physiological and environmental conditions. Background adaptation and
      feeding did not affect plasma SL levels. There was no consistent change in plasma
      SL levels during fasting for 21 days, although increased plasma growth hormone
      levels and decreased condition factor, hepatosomatic index and abdominal fat,
      occurred. Plasma SL concentrations increased during acute stress and also during
      exhaustive exercise resulting from being chased in shallow water. Elevation of
      plasma SL was associated with those of plasma cortisol, Ca2+, phosphate, and
      glucose levels. On the other hand, plasma level of prolactin was not affected in
      the stress and exercise experiments, although plasma GH and Na+ were raised in
      the fish 5 min after the onset of the stress. Our results suggest the involvement
      of SL in calcium and phosphate metabolism, acid-base regulation, or energy
      mobilization in the stressed or exercised trout.

PMID- 7635268
TI  - Distribution of lamprey adrenocorticotropin and melanotropins in the pituitary of
      the adult sea lamprey, Petromyzon marinus.
AB  - Three peptides containing the melanotropin (MSH)-core sequence, YXMXHFRWG, have
      been isolated recently from the pituitary glands of adult sea lampreys
      (Petromyzon marinus) and were tentatively assigned as lamprey adrenocorticotropin
      (ACTH), MSH-A, and MSH-B, respectively. Both MSHs differed significantly from
      gnathostome MSHs and cannot be assigned as alpha-MSH, beta-MSH, or gamma-MSH. The
      aim of the present study was to localize these peptides in the lamprey pituitary
      using antisera generated against synthetic lamprey ACTH1-16, MSH-A, and MSH-B.
      ACTH-like immunoreactivity was found in most cells of the rostal pars distalis
      (RPD) and in a few scattered cells of the proximal pars distalis (PPD). MSH-A
      like immunoreactivity was found in most cells of the RPD, a few scattered cells
      of the PPD, and almost all cells of the pars intermedia (PI). MSH-B-like
      immunoreactivity was found only in the PI, where almost all cells were stained.
      Thus, the topographic distributions of ACTH and MSHs in the lamprey pituitary
      were similar to those in gnathostome vertebrates.

PMID- 7635269
TI  - Developmental changes in melanin-concentrating hormone in Rana temporaria.
AB  - Melanin-concentrating hormone (MCH) is a vertebrate neuropeptide produced in
      hypothalamic neurons. In bony fish, such as trout, MCH acts as a neurohypophysial
      hormone which, once released into the circulation, acts on pigmented skin cells
      with the result that the fish turns pale to camouflage itself against a light
      colored background. In other animals the role of MCH is not clearly established
      but it appears to be a neuromodulator/transmitter within the central nervous
      system rather than a hormone. The present study examines MCH function in the
      grass frog, Rana temporaria. Using immunocytochemistry the location and
      morphology of irMCH neurons were followed, from tadpole to adult frog. In adult
      R. temporaria a group of MCH neurons appeared to comprise small and large-celled
      populations located in the ventral and dorsal infundibular regions, respectively.
      A group of MCH neurons in the preoptic area is proposed, although the perikarya
      were rarely immunostainable. Immunoreactive fibers were seen in various areas of
      the brain, including the olfactory lobes, optic tecta, habenular nucleus, and
      spinal cord. Immunoreactive MCH cells were only visible in midmetamorphic climax
      stages, and cellular morphology suggested low secretory activity until the animal
      first emerged onto land at which time nuclear size and granulation increased
      significantly. No such increase was observed in equivalent stages of the South
      African clawed toad, Xenopus laevis, an animal which is fully aquatic throughout
      its life in contrast to R. temporaria which is terrestrial.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7635271
TI  - Endocrine basis of the reproductive pattern of the Gentoo penguin (Pygoscelis
      papua): winter breeding and extended laying period in northern populations.
AB  - Changes in plasma LH, prolactin, testosterone, estradiol, and progesterone were
      investigated throughout moult and reproduction in free-living male and female
      Gentoo penguins (Pygoscelis papua) at Crozet Island (46 degrees S, 51 degrees E),
      where this species is able to relay after a reproductive failure. In both sexes,
      LH, prolactin, and steroid hormones, remained at basal levels during the moult.
      LH level was highest at the time of arrival at the colony for breeding and,
      although it decreased after courtship, it did not drop at basal value by
      incubation and first chick brooding period. Prolactin peaked for both chick
      brooding periods; replacement clutch was associated with an increased secretion
      of LH, whereas high prolactin levels were maintained. Testosterone, in male, and
      estradiol, in female, peaked during courtship I and chick brooding II;
      progesterone, in female, peaked during courtship I and II. These hormonal
      patterns are consistent with those observed in passerine species which are also
      able to relay after a reproductive failure. Winter breeding observed at Crozet
      Island might reflect the extreme adaptive capacity of Gentoo penguin species.

PMID- 7635270
TI  - Immunocytochemical and morphometric study of TSH, PRL, GH, and ACTH cells in Bufo
      arenarum larvae with inhibited thyroid function.
AB  - Changes in the pituitary cells involved in amphibian metamorphosis were studied
      in Bufo arenarum tadpoles with inhibited thyroid function. After hatching, larvae
      were treated for 5 months with potassium perchlorate (KClO4), a goitrogenic
      substance known to prevent absorption of iodine from water or food, resulting in
      impaired thyroid hormone synthesis. Treated larvae continued to grow but halted
      their development in premetamorphosis, showing hyperplastic thyroid glands with
      disorganized follicles lacking colloid. Thyrotrop (TSH), lactotrop (PRL),
      somatotrop (GH), and corticotrop (ACTH) cells were stained immunocytochemically
      and the changes observed were evaluated morphometrically using an automatic image
      analyzer. Pars distalis volume increased in treated larvae. Morphometric results
      showed that, in treated tadpoles, TSH and PRL cell populations and cell volumes
      increased compared to normal larvae at the same stage. Changes in the GH and ACTH
      cell morphometry were slight. These results indicate that in Bufo tadpoles, after
      chronic thyroid hormone withdrawal, TSH, PRL, GH, and ACTH cells are able to
      develop and that thyroid hormones exert a strong feedback control on the
      synthesis and storage of TSH and PRL.

PMID- 7635272
TI  - N-terminal and C-terminal fragments of the hormone stanniocalcin show
      differential effects in eels.
AB  - The effects of an N-terminal, a C-terminal, and a mid-fragment of stanniocalcin,
      the primary hypocalcemic hormone in fish, on plasma total and free (ionic)
      calcium levels and whole animal calcium influx were tested in eels. Both the N-
      and the C-terminal fragments were hypocalcemic, causing 18 and 12% reduction in
      plasma calcium in stanniectomized eels, respectively. With both fragments the
      hypocalcemic action is transient. The hypocalcemia caused by the C-terminal
      fragment, although more rapid, is not as pronounced as the hypocalcemic action of
      the N-terminal fragment. Only the C-terminal fragment reduced calcium influx. The
      hypocalcemic activity of the C-terminal fragment then can be explained by its
      effect on calcium influx. The N-terminal fragment appears to function in a
      different manner. The mid-fragment has no effect on plasma calcium or calcium
      influx. The different parts of the hormone are concluded to have different
      effects.

PMID- 7635273
TI  - In vitro incorporation of [14C]glycine into muscle protein of gulf killifish
      (Fundulus grandis) in response to insulin-like growth factor-I.
AB  - The effect of recombinant human insulin-like growth factor I (rhIGF-I) on protein
      synthesis was studied in vitro in the muscle of a teleost fish. Protein synthesis
      was assessed by the incorporation of [14C]glycine into protein. rhIGF-I
      stimulated [14C]glycine incorporation in a dose-dependent manner. The minimal
      effective dose was 0.1 ng/ml and maximal stimulation was obtained with 1 ng/ml. A
      high concentration (100 ng/ml) was ineffective. Treatment with 1 ng/ml rhIGF-I
      produced a significant response after 3 hr of incubation and the greatest
      stimulation was observed after 6 hr. Responsiveness of muscle tissue to IGF-I
      examined at three different times (0, 6, and 12 hr after light onset, LD 12:12)
      was greatest at light onset. These results provide evidence that IGF-I may have a
      role in the regulation of growth in fish and that its activities are dose and
      time-of-day dependent.

PMID- 7635274
TI  - A passive immunization technique against the teleost hypocalcemic hormone
      stanniocalcin provides evidence for the cholinergic control of stanniocalcin
      release and the conserved nature of the molecule.
AB  - An in vivo bioassay based on 45Ca uptake from the ambient medium was used to test
      the efficacy of serum from rabbits immunized against trout stanniocalcin to
      passively immunize trout, tilapia, American eel, and guppy against endogenous
      stanniocalcin. The passive immunization was effective in all species. The fact
      that this procedure worked under both homologous and heterologous conditions, and
      in fish from different taxonomic infradivisions, is consistent with the view that
      the stanniocalcins in the four species examined share common antigenic
      determinants. The trout stanniocalcin antiserum had no effect on whole body
      calcium uptake (inCa2+) in stanniectomized eels, indicating that the effect of
      the antiserum was dependent on the presence of functional Stannius corpuscles.
      The technique was then used to show that the inhibitory effects that calcium
      loading and the injection of the cholinoreceptor agonist carbachol have on inCa2+
      probably involve a catecholamine-induced release of endogenous stanniocalcin from
      the Stannius corpuscles.

PMID- 7635276
TI  - Size-dependent, sex-dependent, and seasonal changes in insulin-like growth factor
      I in the loggerhead sea turtle (Caretta caretta).
AB  - This study examines size-dependent, sex-dependent, and seasonal fluctuations in
      plasma insulin-like growth factor-I (IGF-I) concentrations in loggerhead sea
      turtles (Caretta caretta). Loggerhead turtles (n = 158) were captured in shrimp
      trawler nets during a 12-month survey in Cape Canaveral Channel, Florida. Plasma
      samples were analyzed using a validated heterologous radioimmunoassay. Large
      turtles (> 75 cm straight-line carapace length) had significantly higher plasma
      IGF-I concentrations than small turtles (< or = 75 cm; P < 0.0001). Plasma IGF-I
      concentrations did not vary seasonally in small turtles, but large turtles had
      significantly higher plasma IGF-I concentrations during the spring and summer
      months (P < 0.005). Within the large turtles, adult males had significantly lower
      IGF-I concentrations than females and subadult males (P < 0.05). These results
      and a review of loggerhead turtle natural history suggest that the seasonal
      fluctuations in plasma IGF-I of adult turtles are due to elevated IGF-I levels in
      reproductively active female turtles. Further research is needed to examine
      correlations between reproductive activities and plasma IGF-I concentrations in
      reptiles.

PMID- 7635275
TI  - Immunodetection of parathyroid hormone-related protein in plasma and tissues of
      an elasmobranch (Scyliorhinus canicula).
AB  - We have used antiserum to human parathyroid hormone-related protein (PTHrP) (1
      16) to examine tissues and plasma of the dogfish (Scyliorhinus canicula) for the
      presence of immunoreactive PTHrP (irPTHrP). The plasma contained high
      concentrations of irPTHrP (9.34 +/- 0.37 pM), comparable to levels in humans with
      hypercalcaemia of malignancy. Other tissues with irPTHrP included brain neurones;
      epithelial cells of the saccus vasculosus, kidney, rectal gland and choroid
      plexus; and cells of the pituitary pars distalis. PTHrP was not detected in gut,
      skin, oviduct, and gill epithelia, nor in branchial cartilage. The principal
      source(s) of plasma PTHrP is not known.

PMID- 7635277
TI  - Motoo Kimura (1924-1994).

PMID- 7635278
TI  - Regulation of HIS4 expression by the Saccharomyces cerevisiae SIN4
      transcriptional regulator.
AB  - The yeast SIN4 gene functions in the transcriptional activation and repression of
      diverse yeast genes. Previous experiments suggest a sin4 mutation affects
      chromatin structure and thus alters transcriptional regulation. In this report we
      show that SIN4 is required for full expression of the HIS4, Ty1, and MAT alpha
      genes, in addition to the previously described SIN4-dependence of CTS1
      expression. All of these genes contain within their promoters a binding site for
      the Rap1p transcriptional regulator. However, SIN4 does not play a direct role
      either in transcriptional activation or repression by Rap1p. The HIS4 gene can be
      activated by either of two pathways, the basal or the inducible pathway, and
      experiments are described that show that a sin4 mutation affects both pathways.
      It was shown previously that mutation of the Rap1p binding site in the HIS4
      promoter causes a similar effect on HIS4 expression and that this promoter
      mutation also causes a change in chromatin structure. The SNF2/SWI2 gene is also
      required for full HIS4 expression, and we show that a sin4 snf2 double mutant is
      not synergistic compared to either single mutant. We show that nucleosomes are
      positioned at the HIS4 promoter and that this positioning is disrupted in a snf2
      mutant but not in a sin4 mutant. These findings suggest that SIN4 plays a
      distinct role in transcriptional regulation.

PMID- 7635279
TI  - Suppression of a new allele of the yeast RAD52 gene by overexpression of RAD51,
      mutations in srs2 and ccr4, or mating-type heterozygosity.
AB  - The RAD52 gene of Saccharomyces cerevisiae is involved both in the
      recombinational repair of DNA damage and in mitotic and meiotic recombination. A
      new allele of rad52 has been isolated that has unusual properties. Unlike other
      alleles of rad52, this allele (rad52-20) is partially suppressed by an srs2
      deletion; srs2 mutations normally act to suppress only rad6 and rad18 mutations.
      In addition, although haploid rad52-20 strains are very X-ray sensitive, diploids
      homozygous for this allele are only slightly X-ray sensitive and undergo normal
      meiosis and meiotic recombination. Because rad52-20 diploids homozygous for
      mating type are very X-ray sensitive, mating-type heterozygosity is acting to
      suppress rad52-20. Mating-type heterozygosity suppresses this allele even in
      haploids, because sir mutations, which result in expression of the normally
      silent mating-type cassettes, were identified among the extragenic revertants of
      rad52-20. A new allele of srs2 and alleles of the transcriptional regulatory
      genes ccr4 and caf1 were among the other extragenic revertants of rad52-20.
      Because other researchers have shown that the RAD51 and RAD52 proteins interact,
      RAD51 on a high copy number plasmid was tested and found to suppress the rad52-20
      allele, but RAD54, 55 and 57 did not suppress. The RAD51 plasmid did not suppress
      rad52-1. The rad52-20 allele may encode a protein that has low affinity binding
      to the RAD51 protein. To test whether the selected revertants suppressed rad52-20
      by elevating the expression of RAD51, an integrated RAD51-lacZ fusion was
      genetically crossed into each revertant. Because none of the revertants increased
      the level of RAD51-lacZ, the revertants must exert their effect by one or more
      mechanisms that are not mediated by RAD51.

PMID- 7635280
TI  - KRB1, a suppressor of mak7-1 (a mutant RPL4A), is RPL4B, a second ribosomal
      protein L4 gene, on a fragment of Saccharomyces chromosome XII.
AB  - The mak7-1 mutant loses the killer toxin-encoding M1 dsRNA. MAK7 is RPL4A, one of
      two genes encoding ribosomal protein L4. KRB1 is a dominant suppressor of mak7-1
      that is tightly centromerelinked, but not linked to centromere markers of
      chromosomes I-XVI. Our orthogonal field agarose gel electrophoresis analysis of
      chromosomal DNA from strains with KRB1 shows a novel band of approximately 250
      kb. This band hybridizes with an RPL4B-specific probe, but not an RPL4A (MAK7)
      specific probe. The RPL4B-specific probe also hybridizes to chromosome XII where
      the original RPL4B is located. KRB1 is meiotically linked to this extra
      chromosome. Disruption of either the RPL4B gene on chromosome XII or that on the
      extra chromosome results in loss of the killer phenotype and a decreased
      concentration of free 60S subunits. Thus, the RPL4B on the extra chromosome is
      KRB1 and is active. The extra chromosome contains chromosome XII sequence between
      Lambda 5345 clone (ATCC70558) and Lambda 6639 clone (ATCC71085) of Olson's Lambda
      library, indicating that KRB1 represents a chromosomal rearrangement involving
      chromosome XII and explaining the earlier genetic data.

PMID- 7635281
TI  - Marker-dependent recombination in T4 bacteriophage. IV. Recombinational effects
      of antimutator T4 DNA polymerase.
AB  - Recombinational effects of the antimutator allele tsL42 of gene 43 of phage T4,
      encoding DNA polymerase, were studied in crosses between rIIB mutants.
      Recombination under tsL42-restricted conditions differed from the normal one in
      several respects: (1) basic recombination was enhanced, especially within very
      short distances; (2) mismatch repair tracts were shortened, while the
      contribution of mismatch repair to recombination was not changed; (3) marker
      interference at very short distances was augmented. We infer that the T4 DNA
      polymerase is directly involved in mismatch repair, performing both excision of a
      nonmatched single strand (by its 3'-->5' exonuclease) and filling the resulting
      gap. A pathway for the mismatch repair was substantiated; it includes sequential
      action of endo VII (gp49)-->3'-->5' exonuclease (gp43)-->DNA polymerase (gp43)-
      >DNA ligase (gp30). It is argued that the marker interference at very short
      distances may result from the same sequence of events during the final processing
      of recombinational intermediates.

PMID- 7635283
TI  - Genotypic effects, maternal effects and grand-maternal effects of immobilized
      derivatives of the transposable element mariner.
AB  - The baseline rate of spontaneous integration of the autonomous mariner element
      Mos1 into the germline of Drosophila melanogaster is estimated as 16 +/- 5% (mean
      +/- SE) among fertile G0 flies. However, the transformation rate is reduced
      approximately 20-fold in Mos1 constructs with exogenous DNA in the size range 5
      12 kb inserted into the SacI site. To provide alternative Mos1 helper plasmids
      for transformation experiments, two types of Mos1-promoter fusions were
      constructed: hsp-70:Mos1 and hsp26-Sgs3:Mos1. The former has the Mos1 coding
      region driven by the hsp70 heat-shock promoter; the latter has it driven by the
      basal Sgs3 promoter under the control of the hsp26 female-germline specific
      transcriptional regulator. When introduced into D. melanogaster by P-element
      mediated germline transformation, these elements are unable to transpose or
      excise in the presence of autonomous Mos1-related elements (they are "marooned")
      because the 5' inverted repeat of Mos1 is missing. As expected, the hsp26
      Sgs3:Mos1 fusions exhibit a significantly greater rate of germline excision of a
      target mariner element than do the hsp70:Mos1 fusions. Unexpectedly, the rate of
      excision of target mariner elements induced by hsp26-Sgs3:Mos1 is the same in the
      male germline as in the female germline. Both hsp:Mos1 fusions show strong
      germline expression and a maternal effect of the mariner transposase. A
      significant grand-maternal effect of the hsp:Mos1 fusions was also detected as a
      result of a maternal effect on the germline of the F1 progeny. Among flies
      carrying the promoter fusions inherited maternally, about three-quarters of the
      overall rate of germline excision derives from the direct genotypic effect and
      about one-quarter results from the grand-maternal effect. Despite the strong
      somatic expression of the hsp:Mos1 fusions, mariner transformants carrying a
      white+ reporter gene at the SacI site remained stable in the soma.

PMID- 7635284
TI  - Conservation of brown gene trans-inactivation in Drosophila.
AB  - The mechanism underlying trans-inactivation associated with dominant position
      effect variegation (PEV) of the Drosophila melanogaster brown gene has been
      addressed by a comparison with its D. virilis homologue. This comparison
      revealed: 86% identity between conceptual translation products of the brown gene
      from these two species, functional homology, as the D. virilis gene rescues a D.
      melanogaster null brown mutation, and conservation of the sequences required for
      trans-inactivation, as the D. virilis gene in D. melanogaster is subject to
      dominant PEV. An extended region of sequence similarity upstream of the open
      reading frame is observed. As the D. virilis homologue is functionally
      interchangeable with the D. melanogaster gene, these genes must share regulatory
      sequences as well as protein coding homology. These results support a model in
      which trans-inactivation is mediated by a heterochromatin-sensitive transcription
      factor.

PMID- 7635285
TI  - Further characterization of the Odysseus locus of hybrid sterility in Drosophila:
      one gene is not enough.
AB  - Previously we mapped by genetical and molecular means a gene that contributes to
      hybrid-male sterility between Drosophila mauritiana and D. simulans to the
      cytological interval of 16D. In this report, we refine the mapping of this gene,
      Odysseus (Ods) and show that it can be delineated to a region the size of an
      average gene. We further demonstrate that, while Ods appears to be a discrete
      element, it requires other nearby gene(s) to be cointrogressed to confer full
      hybrid sterility effect. This observation is in agreement with the view that
      reproductive isolation between closely related species of Drosophila is usually
      caused by several genes of weak effect from the same species that interact
      strongly among themselves as well as with the foreign genetic background.

PMID- 7635282
TI  - A genetic analysis of the Suppressor 2 of zeste complex of Drosophila
      melanogaster.
AB  - The zeste1 (z1) mutation of Drosophila melanogaster produces a mutant yellow eye
      color instead of the wild-type red. Genetic and molecular data suggest that z1
      achieves this change by altering expression of the wild-type white gene in a
      manner that exhibits transvection effects. There exist suppressor and enhancer
      mutations that modify the z1 eye color, and this paper summarizes our studies of
      those belonging to the Suppressor 2 of zeste complex [Su(z)2-C]. The Su(z)2-C
      consists of at least three subregions called Psc (Posterior sex combs), Su(z)2
      and Su(z)2D (Distal). The products of these subregions are proposed to act at the
      level of chromatin. Complementation analyses predict that the products are
      functionally similar and interacting. The alleles of Psc define two overlapping
      phenotypic classes, the hopeful and hapless. The distinctions between these two
      classes and the intragenic complementation seen among some of the Psc alleles are
      consistent with a multidomain structure for the product of Psc. Psc is a member
      of the homeotic Polycomb group of genes. A general discussion of the Polycomb and
      trithorax group of genes, position-effect variegation, transvection, chromosome
      pairing and chromatin structure is presented.

PMID- 7635286
TI  - fs (1) Yb is required for ovary follicle cell differentiation in Drosophila
      melanogaster and has genetic interactions with the Notch group of neurogenic
      genes.
AB  - Phenotypic and genetic analyses demonstrate that fs (1) Yb activity is required
      in the soma for the development of a subset of ovarian follicle cells and to
      support later stages of egg maturation. Mutations in fs (1) Yb cause a range of
      ovarian phenotypes, from the improper segregation of egg chambers to abnormal
      dorsal appendage formation. The mutant phenotypes associated with fs (1) Yb are
      very similar to the ovarian aberrations produced by temperature-sensitive alleles
      of Notch and Delta. Possible functional or regulatory interactions between fs (1)
      Yb and Notch are suggested by genetic studies. A duplication of the Notch locus
      partially suppresses the female-sterility caused by fs (1) Yb mutations, while
      reducing Notch dosage makes the fs (1) Yb mutant phenotype more severe. In
      addition, fs (1) Yb alleles also interact with genes that are known to act with
      or regulate Notch activity, including Delta, daughterless, and mastermind.
      However, differences between the mutant ovarian phenotype of fs (1) Yb and that
      of Notch or Delta indicate that the genes do not have completely overlapping
      functions in the ovary. We propose that fs (1) Yb acts as an ovary-specific
      factor that determines follicle cell fate.

PMID- 7635287
TI  - Genetic characterization of ms (3) K81, a paternal effect gene of Drosophila
      melanogaster.
AB  - The vast majority of known male sterile mutants of Drosophila melanogaster fail
      to produce mature sperm or mate properly. The ms(3) K81(1) mutation is one of a
      rare class of male sterile mutations in which sterility is caused by
      developmental arrest after sperm entry into the egg. Previous studies showed that
      males homozygous for the K81(1) mutation produce progeny that arrest at either of
      two developmental stages. Most embryos arrest during early nuclear cycles,
      whereas the remainder are haploid embryos that arrest at a later stage. This
      description of the mutant phenotype was based on the analysis of a single allele
      isolated from a natural population. It was therefore unclear whether this unique
      paternal effect phenotype reflected the normal function of the gene. The genetic
      analysis and initial molecular characterization of five new K81 mutations are
      described here. Hemizygous conditions and heteroallelic combinations of the
      alleles were associated with male sterility caused by defects in embryogenesis.
      No other mutant phenotypes were observed. Thus, the K81 gene acted as a strict
      paternal effect gene. Moreover, the biphasic pattern of developmental arrest was
      common to all the alleles. These findings strongly suggested that the unusual
      embryonic phenotype caused by all five new alleles was due to loss of function of
      the K81+ gene. The K81 gene is therefore the first clear example of a strict
      paternal effect gene in Drosophila. Based on the embryonic lethal phenotypes, we
      suggest that the K81+ gene encodes a sperm-specific product that is essential for
      the male pronucleus to participate in the first few embryonic nuclear divisions.

PMID- 7635288
TI  - Comparison of germline mosaics of genes in the Polycomb group of Drosophila
      melanogaster.
AB  - The genes of the Polycomb group (PcG) repress the genes of the bithorax and
      Antennapedia complexes, among others. To observe a null phenotype for a PcG gene,
      one must remove its maternal as well as zygotic contribution to the embryo. Five
      members of the PcG group are compared here: Enhancer of Polycomb [E(Pc)],
      Additional sex combs (Asx), Posterior sex combs (Psc), Suppressor of zeste 2 [Su
      (z) 2] and Polycomblike (Pcl). The yeast recombinase (FLP) system was used to
      induce mitotic recombination in the maternal germline. Mutant embryos were
      analyzed by staining with antibodies against six target genes of the PcG. The
      loss of the maternal component leads to enhanced homeotic phenotypes and to
      unique patterns of misexpression. E(Pc) and Su(z) 2 mutations had only subtle
      effects on the target genes, even when the maternal contributions were removed.
      Asx and Pcl mutants show derepression of the targets only in specific cell types.
      Psc shows unusual effects on two of the targets, Ultrabithorax and abdominal-A.
      These results show that the PcG genes do not act only in a common complex or
      pathway; they must have some independent functions.

PMID- 7635289
TI  - Heterozygosity mapping of partially congenic lines: mapping of a semidominant
      neurological mutation, Wheels (Whl), on mouse chromosome 4.
AB  - We identified a semidominant, chemically induced, mouse mutation with a complex
      array of abnormal behaviors including bidirectional circling and hyperactivity,
      abnormal circadian rhythmicity and abnormal responses to light. In this report,
      we genetically and phenotypically characterized the circling/waltzing component
      of the abnormal behavior. We mapped the locus controlling this trait by
      heterozygosity mapping of partially congenic lines carrying the mutagenized
      chromosome outcrossed to different inbred strains for three generations. Analysis
      of 68 PCR-based markers in 13 affected individuals indicated that the mutant
      locus, named Wheels (Whl), resides in the subcentromeric portion of mouse
      chromosome 4. The statistical evaluation of data obtained by heterozygosity
      mapping validates this efficient mapping approach. Further characterization of
      the Whl mutation demonstrated that Whl/Whl homozygotes die during embryonic life
      and that the penetrance of circling behavior depends on genetic background.
      Morphological analysis of the inner ears of Whl/+ mice revealed a variable number
      of abnormalities in the sensory and nonsensory portions of their semicircular
      canals. Abnormalities ranged from slight atrophy of one or more cristae to
      complete absence of the lateral crista and canal. The molecular characterization
      of the gene disrupted in the Whl mutation will provide insight into developmental
      mechanisms involved in inner ear formation.

PMID- 7635290
TI  - Molecular genetic characterization of six recessive viable alleles of the mouse
      agouti locus.
AB  - The agouti locus on mouse chromosome 2 encodes a secreted cysteine-rich protein
      of 131 amino acids that acts as a molecular switch to instruct the melanocyte to
      make either yellow pigment (phaeomelanin) or black pigment (eumelanin). Mutations
      that up-regulate agouti expression are dominant to those causing decreased
      expression and result in yellow coat color. Other associated effects are obesity,
      diabetes, and increased susceptibility to tumors. To try to define important
      functional domains of the agouti protein, we have analyzed the molecular defects
      present in a series of recessive viable agouti mutations. In total, six alleles
      (amJ, au, ada, a16H, a18H, ae) were examined at both the RNA and DNA level. Two
      of the alleles, a16H and ae, result from mutations in the agouti coding region.
      Four alleles (amJ, au, a18H, and ada) appear to represent regulatory mutations
      that down-regulate agouti expression. Interestingly, one of these mutations,
      a18H, also appears to cause an immunological defect in the homozygous condition.
      This immunological defect is somewhat analogous to that observed in motheaten
      (me) mutant mice. Short and long-range restriction enzyme analyses of homozygous
      a18H DNA are consistent with the hypothesis that a18H results from a paracentric
      inversion where one end of the inversion maps in the 5' regulatory region of
      agouti and the other end in or near a gene that is required for normal
      immunological function. Cloning the breakpoints of this putative inversion should
      allow us to identify the gene that confers this interesting immunological
      disorder.

PMID- 7635292
TI  - Suppression of recJ exonuclease mutants of Escherichia coli by alterations in DNA
      helicases II (uvrD) and IV (helD).
AB  - The recJ gene encodes a single-strand DNA-specific exonuclease involved in
      homologous recombination. We have isolated a pseudorevertant strain in which recJ
      mutant phenotypes were alleviated. Suppression of recJ was due to at least three
      mutations, two of which we have identified as alterations in DNA helicase genes.
      A recessive amber mutation, "uvrD517am," at codon 503 of the gene encoding
      helicase II was sufficient to suppress recJ partially. The uvrD517am mutation
      does not eliminate uvrD function because it affects UV survival only weakly;
      moreover, a uvrD insertion mutation could not replace uvrD517am as a suppressor.
      However, suppression may result from differential loss of uvrD function: mutation
      rate in a uvrD517am derivative was greatly elevated, equal to that in a uvrD
      insertion mutant. The second cosuppressor mutation is an allele of the helD gene,
      encoding DNA helicase IV, and could be replaced by insertion mutations in helD.
      The identity of the third cosuppressor "srjD" is not known. Strains carrying the
      three cosuppressor mutations exhibited hyperrecombinational phenotypes including
      elevated excision of repeated sequences. To explain recJ suppression, we propose
      that loss of antirecombinational helicase activity by the suppressor mutations
      stabilizes recombinational intermediates formed in the absence of recJ.

PMID- 7635291
TI  - A transgenic mouse assay for agouti protein activity.
AB  - The mouse agouti gene encodes an 131 amino acid paracrine signaling molecule that
      instructs hair follicle melanocytes to switch from making black to yellow
      pigment. Expression of agouti during the middle part of the hair growth cycle in
      wild-type mice produces a yellow band on an otherwise black hair. The ubiquitous
      unregulated expression of agouti in mice carrying dominant yellow alleles is
      associated with pleiotropic effects including increased yellow pigment in the
      coat, obesity, diabetes and increased tumor susceptibility. Agouti shows no
      significant homology to known genes, and the molecular analysis of agouti alleles
      has shed little new light on the important functional elements of the agouti
      protein. In this paper, we show that agouti expression driven by the human beta
      ACTIN promoter produces obese yellow transgenic mice and that this can be used as
      an assay for agouti activity. We used this assay to evaluate a point mutation
      associated with the a16H allele within the region encoding agouti's putative
      signal sequence and our results suggest that this mutation is sufficient to cause
      the a16H phenotype. Thus, in vitro mutagenesis followed by the generation of
      transgenic mice should allow us to identify important functional elements of the
      agouti protein.

PMID- 7635293
TI  - Reduced mtDNA diversity in the Ngobe Amerinds of Panama.
AB  - Mitochondrial DNA (mtDNA) haplotype diversity was determined for 46 Ngobe
      Amerinds sampled widely across their geographic range in western Panama. The
      Ngobe data were compared with mtDNA control region I sequences from two
      additional Amerind groups located at the northern and southern extremes of
      Amerind distribution, the Nuu-Chah-Nulth of the Pacific Northwest and the Chilean
      Mapuche and from one Na-Dene group, the Haida of the Pacific Northwest. The Ngobe
      exhibit the lowest mtDNA control region sequence diversity yet reported for an
      Amerind group. Moreover, they carry only two of the four Amerind founding
      lineages first described by Wallace and coworkers. We posit that the Ngobe passed
      through a population bottleneck caused by ethnogenesis from a small founding
      population and/or European conquest and colonization. Dating of the Ngobe
      population expansion using the Harpending et al. approach to the analysis of
      pairwise genetic differences indicates a Ngobe expansion at roughly 6800 years
      before present (range: 1850-14,000 years before present), a date more consistent
      with a bottleneck at Chibcha ethnogenesis than a conquest-based event.

PMID- 7635294
TI  - Phylogenetic analysis of the mitochondrial genomes from Leber hereditary optic
      neuropathy pedigrees.
AB  - The nucleotide sequences of the mitochondrial genomes from patients with Leber
      hereditary optic neuropathy (LHON) were used for phylogenetic analysis to study
      the origin and population history of pathogenic mitochondrial mutations.
      Sequences of both the coding region (8300 bp) and the more rapidly evolving
      noncoding control region (1300 bp) were analyzed. Patients with the primary LHON
      mutations at nucleotides 3460, 11,778, and 14,484 were included in this study, as
      were LHON patients and non-LHON controls that lacked these primary mutations;
      some of the subjects also carried secondary LHON mutations. The phylogenetic
      analyses demonstrate that primary LHON mutations arose and were fixed multiple
      times within the population, even for the small set of LHON patients that was
      analyzed in these initial studies. In contrast, the secondary LHON mutations at
      nucleotides 4216, 4917, and 13,708 arose once: the mitochondrial genomes that
      carried these secondary mutations formed a well-supported phylogenetic cluster
      that apparently arose 60,000 to 100,000 years ago. Previous studies found
      secondary LHON mutations at a higher frequency among LHON patients than among
      control subjects. However, this finding does not prove a pathogenetic role of
      these mutations in LHON. Instead, the increased frequency is more likely to
      reflect the population genetic history of secondary mutations relative to that of
      primary LHON mutations.

PMID- 7635295
TI  - 5-Fluoroindole resistance identifies tryptophan synthase beta subunit mutants in
      Arabidopsis thaliana.
AB  - A study of the biochemical genetics of the Arabidopsis thaliana tryptophan
      synthase beta subunit was initiated by characterization of mutants resistant to
      the inhibitor 5-fluoroindole. Thirteen recessive mutations were recovered that
      are allelic to trp2-1, a mutation in the more highly expressed of duplicate
      tryptophan synthase beta subunit genes (TSB1). Ten of these mutations (trp2-2
      through trp2-11) cause a tryptophan requirement (auxotrophs), whereas three (trp2
      100 through trp2-102) remain tryptophan prototrophs. The mutations cause a
      variety of changes in tryptophan synthase beta expression. For example, two
      mutations (trp2-5 and trp2-8) cause dramatically reduced accumulation of TSB mRNA
      and immunologically detectable protein, whereas trp2-10 is associated with
      increased mRNA and protein. A correlation exists between the quantity of mutant
      beta and wild-type alpha subunit levels in the trp2 mutant plants, suggesting
      that the synthesis of these proteins is coordinated or that the quantity or
      structure of the beta subunit influences the stability of the alpha protein. The
      level of immunologically detectable anthranilate synthase alpha subunit protein
      is increased in the trp2 mutants, suggesting the possibility of regulation of
      anthranilate synthase levels in response to tryptophan limitation.

PMID- 7635296
TI  - Mu1-related transposable elements of maize preferentially insert into low copy
      number DNA.
AB  - The Mutator transposable element system of maize was originally identified
      through its induction of mutations at an exceptionally high frequency and at a
      wide variety of loci. The Mu1 subfamily of transposable elements within this
      system are responsible for the majority of Mutator-induced mutations. Mu 1
      related elements were isolated from active Mutator plants and their flanking DNA
      was characterized. Sequence analyses revealed perfect nine base target
      duplications directly flanking the insert for 13 of the 14 elements studied.
      Hybridizational studies indicated that Mu1-like elements insert primarily into
      regions of the maize genome that are of low copy number. This preferential
      selection of low copy number DNA as targets for Mu element insertion was not
      directed by any specific secondary structure(s) that could be detected in this
      study, but the 9-bp target duplications exhibited a discernibly higher than
      random match with the consensus sequence 5'-G-T-T-G-G/C-A-G-G/A-G-3'.

PMID- 7635297
TI  - Intraspecific and interspecific variation in 5S RNA genes are decoupled in
      diploid wheat relatives.
AB  - 5S RNAs form part of the ribosome in most organisms. In some, e.g., prokaryotes
      and some fungi, the genes are part of the ribosomal operon, but in most
      eukaryotes they are in tandem arrays of hundreds to thousands of copies separate
      from the main ribosomal array. 5S RNA genes can be aligned across kingdoms. We
      were therefore surprised to find that, for 28 diploid species of the wheat tribe
      (Triticeae), nucleotide diversity within an array is up to 6.2% in the genes, not
      significantly different from that of the nontranscribed spacers. Rates of
      concerted evolution must therefore be insufficient to homogenize the entire
      array. Between species, there are significantly fewer fixed differences in the
      gene than would be expected, given the high within-species variation. In
      contrast, the amount of variation between species in the spacer is the same as or
      greater than that within individuals. This leads to a paradox. High variation
      within an individual suggests that there is little selection on any particular
      gene within an array. But conservation of the gene across species implies that
      polymorphisms are periodically eliminated at a rate approximately equal to or
      greater than that of speciation. Levels of intraspecific polymorphism and
      interspecific divergence are thus decoupled. This implies that selective
      mechanisms exist to eliminate mutations in the gene without also affecting the
      spacer.

PMID- 7635299
TI  - Exact inbreeding coefficient and effective size of finite populations under
      partial sib mating.
AB  - An exact recurrence equation for inbreeding coefficient is derived for a
      partially sib-mated population of N individuals mated in N/2 pairs. From the
      equation, a formula for effective size (Ne) taking second order terms of 1/N into
      consideration is derived. When the family sizes are Poisson or equally
      distributed, the formula reduces to Ne = [(4 - 3 beta) N/(4 - 2 beta)] + 1 or Ne
      = [(4 - 3 beta) N/(2 - 2 beta)] - 8/(4 - 3 beta), approximately. For the special
      case of sib-mating exclusion and Poisson distribution of family size, the formula
      simplifies to Ne = N + 1, which differs from the previous results derived by many
      authors by a value of one. Stochastic simulations are run to check our results
      where disagreements with others are involved.

PMID- 7635298
TI  - Molecular evolution of flower development: diversification of the plant MADS-box
      regulatory gene family.
AB  - Floral homeotic genes that control the specification of meristem and organ
      identity in developing flowers have been isolated from both Arabidopsis thaliana
      and Antirrhinum majus. Most of these genes belong to a large family of regulatory
      genes and possess a characteristic DNA binding domain known as the MADS-box.
      Members of this gene family display primarily floral-specific expression and are
      homologous to transcription factors found in several animal and fungal species.
      Molecular evolutionary analyses reveal that there are appreciable differences in
      the substitution rates between different domains of these plant MADS-box genes.
      Phylogenetic analyses also demonstrate that members of the plant MADS-box gene
      family are organized into several distinct gene groups: the AGAMOUS,
      APETALA3/PISTILLATA and APETALA1/AGL9 groups. The shared evolutionary history of
      members of a gene group appear to reflect the distinct functional roles these
      MADS-box genes play in flower development. Molecular evolutionary analyses also
      suggest that these different gene groups were established in a relatively short
      span of evolutionary time and that the various floral homeotic loci originated
      even before the appearance of the flowering plants.

PMID- 7635300
TI  - Spatial structure of two-locus genotypes under isolation by distance.
AB  - Extensive Monte Carlo simulations are conducted of spatial distributions of two
      locus genotypes in large, continuous populations under isolation by distance
      models. The results show that substantial patches of double homozygotes are
      present in the spatial structures, even when loci are unlinked. The stochastic
      spread of identical two-locus genotypes largely outpowers the tendency for
      recombination to decouple patterns for separate loci. A spatial patch is a large
      area containing mostly one double homozygous genotype in a highly contiguous
      constellation. This patch structure is reflected in high positive spatial
      autocorrelations and large excesses of pairs, or joins, of identical double
      homozygotes at short-to-intermediate distances of spatial separation. Although
      spatial patches of double homozygotes are the dominant spatial feature, and the
      major contributors to overall high levels of autocorrelations among two-locus
      genotypes, other substantial features include areas of concentrations of
      identical genotypes heterozygous at only one locus. One implication of the patch
      structure is the presence of high levels of linkage disequilibrium, caused by
      isolation by distance even for unlinked loci, at some spatial scales; yet the
      disequilibrium in the large total populations is near 0. Thus linkage
      disequilibrium produced by isolation by distance is highly dependent on spatial
      scale. Another implication is that high degrees of spatial structuring and
      autocorrelations are produced for genetic variation controlling quantitative
      traits, at least when the number of loci is relatively small, under a wide range
      of situations, even if the trait is selectively neutral. The significance of the
      results to field studies is also examined.

PMID- 7635301
TI  - The detection of linkage disequilibrium in molecular sequence data.
AB  - Studies of genetic variation in natural populations at the sequence level usually
      show that most polymorphic sites are very asymmetrical in allele frequencies,
      with the rarer allele at a site near fixation. When the rarer allele at a site is
      present only a few times in the sample, say below five representatives, it
      becomes very difficult to detect linkage disequilibrium between sites from tests
      of association. This is a consequence of the numerical properties of even the
      most powerful test of association, Fisher's exact test. Sites with fewer than
      five representatives in the sample should be excluded from association tests, but
      this generally leaves few site pairs eligible for testing. A test for overall
      linkage disequilibrium, based on the sign of the observed linkage disequilibria,
      is derived which can use all the data. It is shown that more power can be
      achieved by increasing the length of sequence determined than by increasing the
      number of genomes sampled for the same total work.

PMID- 7635302
TI  - The dominance theory of Haldane's rule.
AB  - "HALDANE's rule" states that, if species hybrids of one sex only are inviable or
      sterile, the afflicted sex is much more likely to be heterogametic (XY) than
      homogametic (XX). We show that most or all of the phenomena associated with
      HALDANE's rule can be explained by the simple hypothesis that alleles decreasing
      hybrid fitness are partially recessive. Under this hypothesis, the XY sex suffers
      more than the XX because X-linked alleles causing postzygotic isolation tend to
      have greater cumulative effects when hemizygous than when heterozygous, even
      though the XX sex carries twice as many such alleles. The dominance hypothesis
      can also account for the "large X effect," the disproportionate effect of the X
      chromosome on hybrid inviability/sterility. In addition, the dominance theory is
      consistent with: the long temporal lag between the evolution of heterogametic and
      homogametic postzygotic isolation, the frequency of exceptions to HALDANE's rule,
      puzzling Drosophila experiments in which "unbalanced" hybrid females, who carry
      two X chromosomes from the same species, remain fertile whereas F1 hybrid males
      are sterile, and the absence of cases of HALDANE's rule for hybrid inviability in
      mammals. We discuss several novel predictions that could lead to rejection of the
      dominance theory.

PMID- 7635304
TI  - Inversions with deletions and duplications.
AB  - Complex mutational events, including de novo inversion with deletion and
      duplication of sequence, have been observed but are difficult to model. We
      propose that nascent leading-strand misalignment upon the lagging-strand template
      during DNA replication can result in the inversion of sequence. The positioning
      of this misalignment and of the realignment of the leading strand back into the
      leading-strand template will determine if the inversion is accompanied by
      deletion and duplication of sequence. We suggest that such strand misalignment
      realignment events may occur at the replication fork during concurrent DNA
      replication.

PMID- 7635303
TI  - A cladistic analysis of phenotypic associations with haplotypes inferred from
      restriction endonuclease mapping or DNA sequencing. V. Analysis of case/control
      sampling designs: Alzheimer's disease and the apoprotein E locus.
AB  - Present-day associations between haplotypes at a candidate locus and phenotypes
      exist when phenotypically important mutations occurred at some point during the
      evolution of the current array of genetic variation. A cladistic statistical
      design can be defined that focuses power by using the evolutionary history of the
      candidate DNA region. This paper shows how cladistic methodology is used for the
      analysis of case/control data, a common sampling design in genetic/disease
      association studies. A worked example is presented of the associations for
      sporadic early and late-onset forms of Alzheimer's disease with the 19q13.2
      chromosomal region that includes the loci for apoproteins E, CI, and CII. This
      analysis confirms earlier reports of a strong association of the ApoE epsilon 4
      allele with Alzheimer's disease but indicates that it is premature to consider
      this association causal, particularly for early onset cases. Associations were
      also found with the epsilon 2 allele, as previously reported, and with the 1
      allele at the ApoCI locus. However, this analysis indicates that it is
      inappropriate both statistically and medically to use single markers as risk
      predictors when haplotype data are available, even when the mutation leading to
      the marker is identified as having a strong phenotypic association.

PMID- 7635305
TI  - Transposable elements in inbreeding and outbreeding populations.

PMID- 7635306
TI  - The relationship between mating system and lyt element abundance in lycopersicon
      and solanum.

PMID- 7635307
TI  - Genetic and physical interactions between yeast RGR1 and SIN4 in chromatin
      organization and transcriptional regulation.
AB  - The SIN4 and RGR1 genes of Saccharomyces cerevisiae were identified by mutations
      in quite different genetic screens. We have shown that the SIN4 gene product is
      required for proper transcriptional regulation of many genes and that a sin4
      mutation can affect either activation or repression of specific genes. We have
      suggested that this dual nature of SIN4 in transcriptional regulation is due to
      its involvement in chromatin organization. We now report that the role of RGR1 in
      gene regulation is similar to that of SIN4. SIN4 and RGR1 both function as
      negative transcriptional regulators of HO and IME1, and mutations in either gene
      lead to decreased expression of other genes including CTS1. Strains with sin4 or
      rgr1 mutations both have phenotypes similar to those caused by histone mutations,
      including suppression of delta insertion into promoters (Spt- phenotype),
      activation of promoters lacking UAS elements, and decreased superhelical density
      of plasmid DNA molecules. Overexpression of RGR1 suppresses the temperature
      sensitivity due to a sin4 mutation. Finally, we use yeast strains expressing GST
      fusion proteins to demonstrate that the Sin4p and Rgr1p proteins are physically
      associated in vivo. These results indicate that Sin4p and Rgr1p act together in
      vivo to organize chromatin structure and thus regulate transcription.

PMID- 7635308
TI  - Factors that affect the location and frequency of meiosis-induced double-strand
      breaks in Saccharomyces cerevisiae.
AB  - Double-strand DNA breaks (DSBs) initiate meiotic recombination in Saccharomyces
      cerevisiae. DSBs occur at sites that are hypersensitive in nuclease digests of
      chromatin, suggesting a role for chromatin structure in determining DSB location.
      We show here that the frequency of DSBs at a site is not determined simply by DNA
      sequence or by features of chromatin structure. An arg4-containing plasmid was
      inserted at several different locations in the yeast genome. Meiosis-induced DSBs
      occurred at similar sites in pBR322-derived portions of the construct at all
      insert loci, and the frequency of these breaks varied in a manner that mirrored
      the frequency of meiotic recombination in the arg4 portion of the insert.
      However, DSBs did not occur in the insert-borne arg4 gene at a site that is
      frequently broken at the normal ARG4 locus, even though the insert-borne arg4
      gene and the normal ARG4 locus displayed similar DNase I hypersensitivity
      patterns. Deletions that removed active DSB sites from an insert at HIS4 restored
      breaks to the insert-borne arg4 gene and to a DSB site in flanking chromosomal
      sequences. We conclude that the frequency of DSB at a site can be affected by
      sequences several thousand nucleotides away and suggest that this is because of
      competition between DSB sites for locally limited factors.

PMID- 7635309
TI  - Recombination of Ty elements in yeast can be induced by a double-strand break.
AB  - The Ty retrotransposons are the main family of dispersed repeated sequences in
      the yeast Saccharomyces cerevisiae. These elements are flanked by a pair of long
      terminal direct repeats (LTRs). Previous experiments have shown that Ty elements
      recombine at low frequencies, despite the fact that they are present in 30 copies
      per genome. This frequency is not highly increased by treatments that cause DNA
      damage, such as UV irradiation. In this study, we show that it is possible to
      increase the recombination level of a genetically marked Ty by creating a double
      strand break in it. This break is repaired by two competing mechanisms: one of
      them leaves a single LTR in place of the Ty, and the other is a gene conversion
      event in which the marked Ty is replaced by an ectopically located one. In a
      strain in which the marked Ty has only one LTR, the double-strand break is
      repaired by conversion. We have also measured the efficiency of repair and
      monitored the progression of the cells through the cell-cycle. We found that in
      the presence of a double-strand break in the marked Ty, a proportion of the cells
      is unable to resume growth.

PMID- 7635310
TI  - LODs past and present.

PMID- 7635311
TI  - Identification of genes required for alpha 2 repression in Saccharomyces
      cerevisiae.
AB  - Transcriptional repression of the a-specific genes in Saccharomyces cerevisiae
      alpha cells involves the concerted action of several proteins. The homeodomian
      protein alpha 2, together with MCM1, recruits two general transcriptional
      repressors, SSN6 and TUP1, to the promoters of a-specific genes. SSN6 and TUP1
      then mediate repression of the a-specific genes. SIN4, another general negative
      regulator, is required for this repression, but unlike tup1 or ssn6 deletions,
      sin4 deletions cause only partial loss of repression. We have screened for other
      genes required for a-specific gene repression in alpha cells. In addition to
      recovering multiple alleles of previously identified genes required for this
      process (referred to as alpha 2 repression), we have identified four other genes,
      designated ARE1, ARE2, ARE3, and ARE4 (for alpha 2 repression). Recessive
      mutations in the ARE genes cause partial loss of a-specific gene repression and
      cause pleiotropic phenotypes similar to those resulting from mutations in SSN6,
      TUP1, or SIN4, suggesting that the ARE genes are general negative regulators.
      Based on our initial analysis, we propose that two distinct classes of general
      negative regulators cooperate to bring about full levels of alpha 2 repression.
      The sequence of ARE1 revealed that it encodes a CDC28-related protein kinase,
      identical to UME5, and thus suggests that protein phosphorylation plays a role in
      alpha 2 repression.

PMID- 7635313
TI  - [Genomic structure of bacteria: uniformity or diversity?].
AB  - This paper is a survey of data, indicating that, in contrast to widely adopted
      ideas, bacterial chromosomes and plasmids are not only circular, but also linear.
      Moreover, certain bacteria contain at least two different chromosomes per cell.
      Examples of other unusual genome properties in certain representatives of
      bacteria are also considered.

PMID- 7635312
TI  - Genetic analysis of the fimbrin-actin binding interaction in Saccharomyces
      cerevisiae.
AB  - Yeast fimbrin is encoded by the SAC6 gene, mutations of which suppress
      temperature-sensitive mutations in the actin gene (ACT1). To examine the
      mechanism of suppression, we have sequenced 17 sac6 suppressor alleles, and found
      that they change nine different residues, all of which cluster in three regions
      of one of the two actin-binding domains of Sac6p. Two of these clusters occur in
      highly conserved regions (ABS1 and ABS3) that have been strongly implicated in
      the binding of related proteins to actin. The third cluster changes residues not
      previously implicated in the interaction with actin. As changes in any of nine
      different residues can suppress several different act1 alleles, it is likely that
      the suppressors restore the overall affinity, rather than specific lost
      interactions, between Sac6p and actin. Using mutagenesis, we have identified two
      mutations of the second actin-binding domain that can also suppress the act1
      mutations of interest. This result suggests the two actin-binding domains of
      Sac6p interact with the same region of the actin molecule. However, differences
      in strength of suppression of temperature-sensitivity and sporulation indicate
      that the two actin-binding domains are distinct, and explain why second-domain
      mutations were not identified previously.

PMID- 7635314
TI  - [Features of the structure of the 7K-copy of Drosophila MDG4 (gypsy)
      retrotransposon provides evidence that the 7K-subfamily of MDG4 is potentially
      capable of transposition].
AB  - The complete nucleotide sequence of the 7K variant of the gypsy retrotransposon
      of Drosophila melanogaster was determined. This variant belongs to the 7K
      subfamily of gypsy, which was previously considered inactive. All differences
      found in the sequenced 7K copy compared to the transpositionally active 6K
      variants were point mutations. These nucleotide substitutions account for about
      1% of the total base pair number of gypsy. Long terminal repeats (LTR) have the
      highest rate of nucleotide substitutions However, changes in nontranslated
      regions did not involve the promoter region and other supposed cis-acting
      elements. Sixteen amino acid substitutions were found in the coding region of
      gypsy. These substitutions were mainly located on the boarders of potential
      functional domains and within the third open reading frame (ORF3). Comparative
      analysis of structures of these two variants of gypsy suggests the potential
      ability of 7K copies to transpose.

PMID- 7635315
TI  - [Analysis of expression of the RSV-lacZ-gene in transgenic embryos of the loach
      Misgurnus fossilis L. during different variations of injection].
AB  - Several series of microinjection of the RSV-lacZ gene (the Escherichia coli beta
      galactosidase gene under the control of the long terminal repeat of the Raus
      sarcoma virus) into fertilized mud loach eggs were carried out. The expression of
      the transgene in 3-5 day-old fry was shown to depend neither upon the stage of
      fry development at which the RSV-lacZ gene was introduced (early blastodisc, late
      blastodisc, 2-blastomere embryo) nor upon the region of transgene injection
      (blastodisc cytoplasm or egg yolk). Additionally, when injected into yolk, a
      smaller number of transgene expression points were observed and their
      distribution was confined to the surface of the yolk sac. In some experimental
      series, transgene expression was observed in 100% of embryos. The presence of
      exogenous genetic material in one of the experimental series was proved for 100%
      of 5- to 6-week old juveniles, when injected into cytoplasm, and for 67% of
      juveniles, when injected into yolk. This work provides evidence of the
      possibility of 100% transfer and expression of exogenous DNA when transgenic
      loachs are generated by injection into embryos and fry at different stages of
      their development.

PMID- 7635316
TI  - [Mutagenic effect of oxidizing agents on the thermally-induced prophage lambda
      cI857: effect of a system of oxidative stress].
AB  - The lethal and mutagenic effects of hydrogen peroxide H2O (2-20 mM), cumene
      hydroperoxide (0.2-2.0 mM), and potassium permanganate KMnO4 (0.25-1.0 mM) on the
      heat-inducible lambda cI857 prophage were studied under conditions of heat
      induction immediately after the mutagenic treatment of lysogenic cells of
      Escherichia coli oxyR+ or oxyR delta 3. Within the range of the doses used, these
      agents decreased prophage survival by 3-5 orders of magnitude and increased
      mutation frequency by up to 0.2% under the action of hydrogen peroxide and cumene
      hydroperoxide, and up to 1.5% in the case of KMnO4 (in oxyR+ cells). In the
      absence of the inducible OxyR system of oxidative stress, both lethal and
      mutagenic effects of H2O were enhanced. The oxyR delta 3 mutation increased
      lethal and mutagenic effects of cumene hydroperoxide and KMnO4 only at the
      highest concentrations used. Apparently, the OxyR system does not repair lesions
      induced by oxidative agents, but only prevents their formation.

PMID- 7635317
TI  - [Biochemical variability and genetic divergence of the palearctic voles
      (Arvicolidae): subgenus subterranean voles Terricola, true lemmings Lemmus Link,
      1795, pied lemmings Dicrostonyx Gloger, 1841, steppe lemmings Lagurus Gloger,
      1842, and mole voles Ellobius Fischer von Waldheim, 1814].
AB  - Genetic differentiation of 35 vole species, estimated at 18 to 31 biochemical
      loci, allowed us to identify the following phyla of the tribe level: Lemmini,
      Dicrostonychini, Ellobiini, Clethrionomyini, and Microtini. Average genetic
      differentiation between the tribes (D'Nei = 0.977) corresponds to separation of
      the phylogenetic branches in the middle Pleistocene. Tribe Lagurini was shown to
      be contained within Cletrionomyini. Ondatrini was the first branch that diverged
      from the common stem in the Miocene (D = 1.563), prior to the formation of the
      Arvicolidae family. Distribution of genetic distances indicates that family
      radiations comprised two stages, tribal (Pliocene) and specific (Pleistocene).
      Ages of the taxa, estimated by means of the molecular clock, agreed well with
      stratigraphic data. Marked periodicity of divergence in the family confirms the
      concept of punctuated evolution.

PMID- 7635318
TI  - [Induction of transposition of MGE Dm412 using gamma-irradiation of an isogenic
      line of Drosophila melanogaster].
AB  - In an isogenic line of Drosophila, transpositions of mobile genetic elements
      (MGE) Dm412 were induced by gamma-radiation at doses of 300, 800, and 1300 R. The
      rates of induced transpositions were (for each dose, respectively) 3.9 x 10(-3),
      1.0 x 10(-2), and 1.87 x 10(-2) events per occupied site per haploid genome of
      the isogenic line per generation. Thus, the transposition rate increased linearly
      with the radiation dose. The specific rate of gamma-radiation-induced
      transpositions was (1.3 +/- 0.6) x 10(-5) per occupied site per haploid genome of
      the isogenic line per Roentgen per generation. gamma-radiation-induced hot
      transposition sites and haplotypes, very similar to those induced by heat shock,
      were found. It was suggested that the mechanism of temperature induction than to
      the direct mutational effect of gamma-radiation. Estimates of induced
      transposition rates per genome for each dose were calculated as 1.1, 3.0, and 5.6
      events, respectively, per genome per generation. This level probably corresponds
      to the subthreshold level of genomes near the "catastrophic border of
      transpositional losses."

PMID- 7635319
TI  - [Increased mitotic crossing over of heterochromatin in the first cleavage
      division of Drosophila melanogaster].
AB  - It is shown that, although no compaction of paracentromeric heterochromatin
      occurs during the first cleavage division in Drosophila melanogaster, the
      frequency of mitotic crossing-over in corresponding chromosome regions is
      increased, as compared to that in euchromatin. Because a similar situation is
      observed at later stages of Drosophila development, at which compact chromatin
      regions become well-manifested, it is concluded that the effect of
      heterochromatin on the frequency of crossing-over does not depend on its packing.
      A positive correlation between crossing-over events in paracentromeric
      heterochromatin and euchromatin was observed. This effect is probably due to the
      formation of a continuous region of somatic synapsis, which facilitates the
      process of mitotic crossing-over. On this basis, it is proposed that the effect
      of heterochromatin on mitotic crossing-over is associated with preferential
      chromosome pairing in the corresponding regions.

PMID- 7635320
TI  - [Molecular-genetic typing of three representatives of the transpalearctic species
      of forest and field mice (Apodemus, Muridae, Rodentia)].
AB  - The genomes of three species of wood mouse (Apodemus falzfeini and A. ponticus
      from the Caucasus and A. argenteus from Japan) were compared by means of
      restriction analysis of nuclear DNA. The species are differentiated from each
      other and from previously studies species. Each species has its species-specific
      features. Within the genus Apodemus, A. ponticus is most closely related to the
      European species A. sylvaticus and A. flavicollis. A. falzfeini has a peculiar
      type of restriction with EcoR I (specific for dispersed repeats) and Hind III
      (specific for satDNA). The genome of this species contains three families of EcoR
      I repeats previously found in various species (European and Asian) of wood mouse
      and Hind III components characteristic of both wood and field mice. A. argenteus
      differs from all other forms of Apodemus, the genome of which contains the 375-bp
      Hind III satellite, by the presence of a EcoR I satDNA fraction consisting of 240
      bp repeating units.

PMID- 7635321
TI  - [Analysis of the allelic polymorphism of four short tandem repeats in a
      population from the northwestern region of Russia].
AB  - Characteristics of the allelic polymorphisms of the trimeric AGC repeat of the
      androgen receptor gene (Xq11-12), exon 1 (AR); the tetrameric ATCT repeat of the
      von Willebrand factor gene (12p12), intron 40 (vWF); the AGAT repeat of the
      hypoxanthine phosphoribosyltransferase gene (Xq26) (HPRT); and the AGAT repeat of
      anonymous DNA sequences of the short arm of chromosome X (STRX1) were studied in
      160 DNA samples from unrelated inhabitants of northwestern Russia using the
      method of polymerase chain reaction. Seventeen, ten, eight, and nine alleles were
      revealed electrophoretically for short tandem repeats of AR, vWF, HPRT, and
      STRX1, respectively. The heterozygosity indices for these repeats were 0.80,
      0.70, 0.54, and 0.58, respectively. The values for AR and vWF correlated with
      those expected, according to the Hardy-Weinberg equilibrium, whereas the values
      for HPRT and STRX1 differed significantly from those theoretically expected. The
      individualization potentials were 0.045, 0.135, 0.095, and 0.061 for the short
      tandem repeats of AR, vWF, HPRT, and STRX1, respectively. The distribution of
      genotypes for the set of these four loci in the population studied was
      determined. The possibilities of using the studied polymorphic marker systems in
      molecular diagnosis of the corresponding monogenic diseases--spinal and bulbar
      muscle atrophy (AR), Lesch-Nyhan disease (HPRT), and von Willebrand disease (vWF)
      -as well as in population human genetics, testing of personal identity, and
      molecular approaches to the estimation of mutagenic activity are discussed.

PMID- 7635323
TI  - [DNA typing of HLA class II genes among the aboriginal inhabitants of Chukotka].
AB  - Polymorphism of class II HLA genes was studied in native Chukotka inhabitants
      with the use of DNA oligotyping. The characteristics of the distribution of
      allelic variants of the loci HLA-DRB1, -DQA1, -DQB1, and -DPB1 were revealed;
      they were similar to those of other Subarctic Mongoloid populations and different
      from those for comparable populations of other climatic and geographic zones. Our
      data suggest that the specific features found for the distributions of some
      alleles of the loci examined are related to the geographic variation in the HLA
      gene system studied.

PMID- 7635322
TI  - [Types of regulatory regions in mitochondrial DNA in eastern Slavs].
AB  - Nucleotide sequences of hypervariable segment I (HVS I) of the mitochondrial DNA
      (mtDNA) control region were determined for 23 eastern Slavs residing in Magadan,
      northeastern Asia. A high diversity of HVS I types was observed: each mtDNA
      analyzed has a unique nucleotide sequence. The types of HVS I revealed were shown
      to be widespread in the Caucasian population. Eight types of HVS I are identical
      to those in Caucasians from the Middle East and southern Europe. Taking into
      account the data obtained on mtDNA types in the world Caucasian population, the
      problem of the origin and differentiation of peoples of the Indo-European
      language family is discussed.

PMID- 7635324
TI  - [Prospects for using the SOS-Chromotest for predicting carcinogenic activity of
      chemical compounds].
AB  - When studying the carcinogenic activity of a compound, one of the basic problems
      is to determine the predictability of the methods used for testing; in our
      opinion, the most promising method is the SOS chromotest. To evaluate the test,
      we sampled 25 substances with a known carcinogenic activity, which had not been
      tested with the SOS chromotest before. Properties of the SOS chromotest were
      analyzed on the basis of a database containing 154 substances at present, which
      are characterized with regard to the presence or absence of a carcinogenic effect
      in rodents. The results are distributed as follows: 121 carcinogens, of which 79
      positively respond to the SOS chromotest; 33 noncarcinogenes, of which 28
      negatively respond to the SOS chromotest. The sensitivity and specificity of the
      SOS chromotest were measured as 65.3 and 84.9%, respectively. Comparing the
      results obtained with the Ames test and with the SOS chromotest, it was shown
      that the tests were similar in sensitivity and specificity. A similar
      predictability of both methods was also recorded.

PMID- 7635325
TI  - Venous disease: how to heal and prevent chronic leg ulcers.
AB  - Venous disease accounts for up to 90% of all cases of chronic leg ulcers.
      Patients with venous disease have relatively unhealthy, ischemic tissue in the
      lower legs, and slight trauma often initiates an ulcer. Symptoms include leg
      swelling, which is often unilateral and persistent, and a dull ache that worsens
      with standing, walking, or sitting with the legs down. Approximately 50% of
      patients have a history of deep vein thrombosis. A careful history and
      examination can rule out other causes and guide appropriate therapy as well as
      prophylaxis against progressive disease. Elevation, compression, occlusion, and
      debridement are the mainstays of treatment. Ulcer healing is gradual, often
      requiring weeks to months of therapy. Preventing recurrence requires careful
      attention to compression; surgery may be indicated.

PMID- 7635326
TI  - Osteoporosis: drug and nondrug therapies for the patient at risk.
AB  - Preventing bone loss and avoiding fractures are the most effective therapies for
      osteoporosis. Nondrug measures include weight-bearing exercise, adequate calcium
      intake, and the prevention of falls. Estrogen replacement therapy can protect
      bone from rapid demineralization typical of the early post-menopausal period. New
      research has provided more data on estrogen's safety and efficacy. Calcitonin is
      an option when estrogen is contraindicated. Although calcitonin requires frequent
      injections, it does provide some analgesic effect for patients with osteoporosis
      related fracture. Fluoride and etidronate have shown promise but remain
      investigational due to questions about long-term effects on bone mass. Potent
      third-generation bisphosphonates are being studied and may be available soon.

PMID- 7635328
TI  - Pap smears: diagnostic and screening formats.

PMID- 7635327
TI  - Late-life depression: when and how to intervene.
AB  - Late-life depression ranges from mild to severe and can lead to significant
      physical and social limitations. Up to one-third of patients with medical
      disorders also suffer from depressive symptoms. Differential diagnosis of
      depression is often confounded by medical conditions that impair cognitive
      functioning, such as Alzheimer's disease and vascular dementia. Depression is a
      modifiable risk factor for suicide in old age. Once diagnosed, depression is a
      highly treatable disease. Treatment modalities include psychotherapy,
      antidepressants, and electroconvulsive therapy for intractable cases. Many
      patients are now being treated in primary care settings, due to managed care
      limits on referrals and to patient reluctance to seek psychiatric care.

PMID- 7635329
TI  - Medicare: what every physician should know.

PMID- 7635330
TI  - [Industrial waste: ecologic and hygienic problems].

PMID- 7635331
TI  - [Analysis of morbidity of railway transport workers in relation to the level of
      magnetic field due to traction engines].

PMID- 7635333
TI  - [Effects of mineral contents of a ration on indicators of radiation resistance of
      the body].
AB  - Relationship between the levels of calcium, potassium, and iron in rations and
      the indexes of antioxidant system of rats exposed to prolonged 137Cs loading was
      studied. Calcium deficiency was found to weaken the antioxidant system. Increased
      intake of potassium and iron provide high level of adaptation of the antioxidant
      system.

PMID- 7635332
TI  - [Bioelectrical activity of the myocardium and cardiac pump function in workers
      engaged in lead production].

PMID- 7635334
TI  - [Effects of food rations with different levels of calcium on parameters of
      cellular immunity of sensitized rats].
AB  - Effect of alimentary calcium on cellular immunity of rats with allergic
      dermatitis was studied. Calcium-deficient rations were found to be conducive to
      decrease of the metabolic activity of rat lymphocytes, whereas normal or
      increased intake of calcium provided a sufficiently high level of specific
      response.

PMID- 7635335
TI  - [Hygienic expert evaluation in the standardization of the use of polymer and
      other materials in food industry].
AB  - Numerous polymers and other materials to be used in food industry should be
      rapidly assessed from a hygienic view-point. Experience gained in this sphere
      permits us recommend a method for rapid hygienic expert evaluation of such
      materials. Approaches to, and potentialities of such expert evaluation are
      demonstrated.

PMID- 7635336
TI  - [Rapid experimental assessment of biologic effects of polymers intended for
      contact with food products].
AB  - Analyzing their findings and published data, the authors demonstrate the
      possibility of rapid toxicologic assessment of polymers intended for contact with
      food. Polycarbonate and polysulfone were used in the studies.

PMID- 7635337
TI  - [Study of adolescent morbidity at a construction vocational school in Moscow].

PMID- 7635338
TI  - [Etiology as a theoretical component of hygiene science].
AB  - Analysis of experience gained by the Russian hygienic science, actual hygienic
      materials, and authors' own data show that hygiene as science can be justly
      considered as a theoretical scientific branch engaged in fundamental problems of
      medical science. Moreover, etiology of professional and ecology-caused diseases
      is one of the most important aspects of theoretical basis of hygienic science.

PMID- 7635339
TI  - [The age of appearance of first menses in women of different regions of Russia].

PMID- 7635340
TI  - [Resorption coefficients and prevention of Pu-239 oxide entry through microtrauma
      of the skin].
AB  - The resorption coefficients of 239Pu were from (3.0 +/- 0.3) x 10(-4) to (6.3 +/-
      1.4) x 10(-4) after contamination of skin microwounds of rats with plutonium
      oxides. Effective periods of the radionuclide accumulation in the organism were
      from 0.18 to 0.48 days. Disactivation of microinjuries with 3% hydrogen peroxide
      solution followed by electrocoagulation of the involved skin sites helped reduce
      the level of 239Pu in the tested skin site by 12.5 times, and by 4.5 to 7.5 times
      in the skeleton and liver. These measures, in combination with a 64-day course of
      pentacin and zincacin injections, helped reduce the level of the radionuclide in
      the organism 12-fold.

PMID- 7635342
TI  - [Hygienic assessment of exploitation of ships of design 19620 equipped for mixed
      sea and inland navigation].

PMID- 7635341
TI  - [Possible violations of ecological and hygienic balance by surface-active agents
      under conditions of complex anthropogenic environmental pollution (review)].

PMID- 7635343
TI  - [Liver and membrane protective properties of tea catechins in alcoholic
      intoxication].

PMID- 7635344
TI  - [Hygienic studies in People's Republic of China (review)].

PMID- 7635345
TI  - [Comparative assessment of methods of studying effects of industrial noise under
      conditions of present-day forms of labor].

PMID- 7635346
TI  - [Sanitary and hygienic care of Armed Forces and civilians during Great Patriotic
      War (the 50th anniversary of the Great Victory)].

PMID- 7635347
TI  - [Synthetic outlook to new ideas in hygienic standardization].

PMID- 7635348
TI  - [Physiological approach as the basis of hygienic standardization (current status
      and prospects)].

PMID- 7635349
TI  - [Standardization of the chemical-pharmaceutical industry products in water with
      consideration of their pharmacological and hygienic properties].
AB  - Results of experimental substantiation of hygienic standards of 30 drugs in water
      and analysis of published data showed that drugs should be referred to highly
      hazardous pollutants of the environment. Criteria and indexes of pharmacologic
      activity were proposed for use in norm-setting studies.

PMID- 7635350
TI  - Diaspirin crosslinked hemoglobin (DCLHb): absence of increased free radical
      generation following administration in a rabbit model of renal ischemia and
      reperfusion.
AB  - In control rabbits, a renal ischemia of 60 min followed by 10 min of reperfusion
      resulted in an enhanced free radical production in cortical tissue, as assessed
      by a significant decrease of free glutathione (42%), protein-bound GSH (17%), and
      vitamin E (49%). In contrast, catalase or glutathione peroxidase activities were
      not affected by these experimental conditions. Free radical production in this
      model was also measured directly using electron spin resonance (ESR) spectroscopy
      associated with a PBN (alpha-phenyl N-tert-butyl-nitrone) spin trap agent in the
      venous blood arising from the ischemic kidney. The signal consisted of a triplet
      of doublets. In contrast, no signal could be detected in control blood samples
      taken prior to inducing ischemia. The burst of free radical production occurred
      in the early phase after restoration of flow in the kidneys rendered ischemic, as
      evidenced by a signal of weak intensity which generally appeared within the third
      minute after reperfusion and progressively increased to form a well-defined
      asymmetric signal following 10 min of reperfusion. The precise nature of free
      radicals trapped by the PBN agent remains, however, to be elucidated, but
      analysis of the coupling constants (aN = 14.5-15 G; a beta H = 2.5-3 G) and
      asymmetry of the central doublets suggests that the ESR signal may arise from a
      nitorxy-radical adduct resulting from the spin trapping by PBN of both oxygen- or
      carbon-centered radicals of lipid origin. As evidenced by both direct and
      indirect measurements, exchange of rabbit blood immediately after inducing renal
      ischemia with 30 ml/kg of Diaspirin Crosslinked Hemoglobin (7.5 g/dl in lactated
      electrolyte) or human serum albumin (7.5 g/dl in lactated electrolyte) did not
      exacerbate free radical production mediated by an ischemia reperfusion
      phenomenon, a typical situation found in a resuscitation setting.

PMID- 7635351
TI  - From free radicals to electronically excited species.
AB  - Biologically/medically important compounds, when metabolized, can generate free
      radicals from which electrically excited products--often in the triplet state-
      are generated. Peroxidases are particularly apt to catalyze such processes, which
      usually entail oxidations by electron transfer. In the latter case, the
      chemiluminescence may derive from peroxyl and alkoxyl radicals or excited states
      derived from dioxetanes. Besides peroxidases, prostaglandin-H synthase and
      lipoxygenase may catalyze the formation of excited carbonyls. The pronounced
      similarity in the chemical behavior and reactivity of radicals and excited
      species derives in part from the biradical nature of the latter. Usually in
      analyzing the biological effects of xenobiotics, only radicals and/or reactive
      ground state products have been considered. However, in such processes the
      generation of excited species is possible, which should be tested for by direct
      and/or sensitized emission or by photochemical transformation.

PMID- 7635352
TI  - Desferrioxamine inhibition of the hydroxyl radical-like reactivity of
      peroxynitrite: role of the hydroxamic groups.
AB  - Nitric oxide reacts with superoxide to form peroxynitrite, a strong oxidizing
      species. Peroxynitrite can either directly oxidize molecules such as thiols or
      protonate to peroxynitrous acid, which can yield an oxidant with a reactivity
      similar to that of hydroxyl radical in a transition metal-independent mechanism.
      This oxidative chemistry of peroxynitrite, however, is inhibited by the metal
      chelator desferrioxamine. Indeed, desferrioxamine, was a potent inhibitor of
      dimethylsulfoxide, hydrogen peroxide, 5,5-dimethyl-1-pyrroline-N-oxide, and
      luminol oxidation, whereas the metal chelator diethylenetriaminepentaacetic acid,
      and ferrioxamine, the iron complex of desferioxamine, were not. Two other
      hydroxamates, acetohydroxamate and salicylhydroxamate, were also effective
      inhibitors. Stopped-flow experiments showed that there is no direct reaction
      between peroxynitrite anion or cis-peroxynitrous acid with desferrioxamine.
      Electron paramagnetic resonance (EPR) studies showed the formation of the
      desferrioxamine nitroxide radical in incubations containing desferrioxamine, but
      not ferrioxamine, indicating that the hydroxamic group acts as a one-electron
      donor to peroxynitrite-derived oxidants. Taken together, our results led us to
      propose that desferrioxamine can inhibit the oxidative chemistry of peroxynitrite
      by reaction of the hydroxamic acid moieties with trans-peroxynitrous acid.

PMID- 7635353
TI  - Decrease of blood cholesterol and stimulation of antioxidative response in
      cardiopathy patients treated with endovenous ozone therapy.
AB  - Patients with cardiac infarction show a decrease in glutathione peroxidase and
      superoxide dismutase activities, which are beginners in the scavenger processes
      of lipid peroxide and superoxide radicals, respectively. In this study, we
      investigate the effects of endovenous ozone therapy on serum lipid pattern and on
      antioxidant defense system, such as te glutathione redox one, in the blood of
      patients with myocardial infarct. Twenty-two patients who had an infarction,
      between 3 months and 1 year before the study, were treated with ozone by
      autohemotherapy during 15 sessions. A statistically significant decrease in
      plasma total cholesterol and low density lipoprotein was observed. High
      biologically significant increases on erythrocyte glutathione peroxidase and
      glucose 6-phosphate dehydrogenase activities were found. There was no change in
      plasma lipid peroxidation level. It was concluded that endovenous ozone therapy
      in patients with myocardial infarction has a beneficial effect on blood lipid
      metabolism, provoking the activation of antioxidant protection system.

PMID- 7635354
TI  - Inactivation of Cu,Zn-superoxide dismutase by free radicals derived from ethanol
      metabolism: a gamma radiolysis study.
AB  - The reactions of free radicals derived from ethanol metabolism with Cu,Zn SOD
      were studied. 1-Hydroxyethyl radicals were generated by gamma radiolysis of a N2O
      saturated ethanolic solution (10(-2) M) in phosphate buffer (10(-3) M, pH 7.4).
      To generate acetyl radicals by gamma radiolysis, we used ethylene glycol (10(-2)
      M) in phosphate buffer (10(-3) M, pH 7.4). This allows us to avoid the use of
      acetaldehyde, which may be toxic toward various cellular constituents. We have
      previously reported that HO. radicals reacting with either acetaldehyde or
      ethylene glycol produce the same free radicals (Santiard et al., 1991, J. Chim.
      Phys. 88, 967-976). the rate constant reaction of 1-hydroxyethyl free radicals
      with Cu,Zn-SOD was measured separately by competition kinetics with the spin
      trapping agent alpha-(4-pyridyl 1-oxide) N-terbutylnitrone (4-POBN), after having
      measured the rate constant of scavenging of 1-hydroxyethyl free radicals by 4
      POBN in the absence of SOD. We found k1 (4-POBN + 1-hydroxyethyl radical) = 4.2
      10(5) M-1 s-1 and kR (SOD + 1-hydroxyethyl radical) = 6.8 10(5) M-1 s-1). 1
      Hydroxyethyl or acetyl radicals produced dose-dependent Cu,Zn-SOD inactivation.
      The inactivation rate constant of Cu,Zn-SOD by 1-hydroxyethyl radicals is ki =
      1.13 10(4) M-1 s-1. Free radicals derived from ethanol metabolism can thus react
      SOD leading to enzyme inactivation, besides the fact that the reactivities of 1
      hydroxyethyl radicals with 4-POBN and with proteins such as Cu,Zn SOD are of the
      same order of magnitude could explain the difficulties to trap in vivo these
      radicals.

PMID- 7635355
TI  - An in vitro EPR study of the free-radical scavenging actions of the lazaroid
      antioxidants U-74500A and U-78517F.
AB  - Oxygen-based free radicals have been shown to play a major role in the acute
      destruction of neurons following cerebral ischemia and may be involved in the
      chronic neurodegeneration seen in Parkinson's disease, Alzheimer's disease, and
      other conditions characterized by the progressive death of neurons in the central
      nervous system. Drugs belonging to a group of antioxidant compounds, collectively
      known as the lazaroids, have strong neuroprotective effects in experimental
      models of acute ischemia. However, the specific mechanisms by which these drugs
      reduce the harmful actions of free radicals have not been established. Using
      electron paramagnetic resonance (EPR) spectroscopy with spin trapping, we
      investigated the interaction of U-74500A, a first-generation lazaroid, and U
      78517F, a second-generation lazaroid, with two species of oxygen-based free
      radicals in aqueous solution and with the stable nitrogen-based free radical
      diphenylpicrylhydrazyl in dimethyl sulfoxide. Superoxide radicals were generated
      by the action of xanthine oxidase on hypoxanthine. Hydroxyl radicals were
      generated by the Fenton reaction involving aqueous ferrous iron and hydrogen
      peroxide. Both lazaroids reduce the EPR signal of all three radicals, but the
      drugs differ in potency and relative radical selectivity. These observations are
      consistent with the lazaroids being scavengers of oxygen-based and nitrogen-based
      free radicals and suggest that the neuroprotective actions of the lazaroids in
      cerebral ischemia may involve direct interactions of the lazaroids with several
      different species of free radicals.

PMID- 7635356
TI  - Hydrogen peroxide as a potent bacteriostatic antibiotic: implications for host
      defense.
AB  - Host defense against bacterial pathogens in higher organisms is mediated in part
      by the generation of reactive oxygen species (ROS) by PMN. In this study, we
      determined the following effects of exposure of constant concentrations of H2O2
      on E. coli in a culture continuously monitored for H2O2 concentration, numbers,
      and viabilities of cells: (1) E. coli growth rates monitored for 1 h were
      profoundly affected by concentrations of H2O2, between 25-50 microM. (2) Complete
      bacteriostasis was observed at 100 microM. (3) Significant cell killing was not
      observed until the concentration of H2O2 was greater than 500 microM. (4)
      Bacteriostatic (25-50 microM) concentrations of H2O2 appeared not to be toxic to
      human skin fibroblasts for a 2-h exposure. (4) Bacteriostasis by H2O2 could not
      be explained by metabolic inhibition, because intracellular ATP levels were not
      compromised at bacteriostatic doses of H2O2. (5) Measurements of H2O2
      concentrations in subcutaneous abscess fluid infected with both E. coli and S.
      aureus indicated prevailing concentrations of the oxidant consistent with a
      proposed role of H2O2 in host defense.

PMID- 7635357
TI  - The reaction of 4-hydroxy-2-nonenal with N alpha-acetyl-L-histidine.
AB  - The reaction of 4-hydroxy-2-nonenal and N alpha-acetyl-L-histidine was studied in
      pH 7.1 phosphate buffer. The main product isolated was assigned a cyclic
      hemiacetal structure formed by the addition of one of the imidazole nitrogen
      atoms to the alpha,beta-unsaturated aldehyde system of 4-hydroxy-2-nonenal. This
      structural assignment was based on the analyses of the NMR and mass spectral data
      of two derivatives obtained from the cyclic hemiacetal. The establishment of this
      cyclic hemiacetal structure supports the proposal made by Uchida and Stadtman6
      that 4-hydroxy-2-nonenal modified histidyl residues in insulin by a Michael
      reaction.

PMID- 7635358
TI  - Interaction of flavonoids with ascorbate and determination of their univalent
      redox potentials: a pulse radiolysis study.
AB  - Concurrent pulse-radiolytic generation of flavonoid aroxyl radicals and ascorbyl
      radicals causes a complex kinetic interplay of competing and parallel reactions.
      Evaluation by "kinetic modelling," that is, taking into account all possible
      reactions by a set of differential equations, allowed us to determine equilibria
      constants for the univalent steps by a novel method. From these kinetic data we
      were able to calculate the redox potentials for dihydroquercetin, quercetin,
      rutin (a quercetin 3-glycoside), kaempferol, fisetin, and luteolin. Despite the
      limited number of substances, two structural criteria became apparent: all
      substances containing the B-ring catechol group and the 2,3-double bond have a
      higher redox potential than ascorbate and are consequently able to oxidize it to
      the ascorbyl radical. With fisetin and kaempferol having values very similar to
      ascorbate, only the flavanone dihydro-quercetin was capable of reducing the
      ascorbyl radical, thus fulfilling the so-called "ascorbate-protective" function,
      originally proposed by Szent-Gyorgyi. While flavonoids are effective radical
      scavengers, these rather high redox potentials for most flavonols may explain
      their occasional prooxidative behavior.

PMID- 7635359
TI  - Antioxidant enzyme levels as a function of growth state in cell culture.
AB  - Manganese superoxide dismutase (MnSOD) levels were monitored as a function of
      time in culture to determine whether these levels were altered at logarithmic
      growth versus when the cells exhibited density limitation of growth. For
      comparison, activities of the antioxidant enzymes copper, zinc superoxide
      dismutase (CuZnSOD), catalase, and glutathione peroxidase were also evaluated.
      Four cell lines were studied, two of which exhibited density limitation of growth
      and two of which did not. Each cell line showed a unique antioxidant enzyme
      profile. The two cell lines that showed density limitation of growth also
      demonstrated induction of MnSOD at the time when the cells stopped proliferating
      in culture, whereas the other two cell lines did not show induction of MnSOD.
      There was no strict correlation between density limitation of growth and
      activities of the other antioxidant enzymes. To determine whether SOD varied with
      various phases of the cell cycle, NIH/3T3 cells were synchronized using serum
      starvation, and then SOD activities were measured during quiescence (G0) and the
      phase of DNA synthesis (S-phase). MnSOD was decreased during S-phase compared
      with G0, whereas CuZnSOD was increased during S-phase compared with G0,
      demonstrating alteration of SOD activities with varying phases of the cell cycle.
      This study suggests the possibility that increased MnSOD may correlate with
      decreased cell proliferation and suggests significant alterations in SOD
      activities during the cell cycle.

PMID- 7635361
TI  - Age- and peroxidative stress-related modifications of the cerebral enzymatic
      activities linked to mitochondria and the glutathione system.
AB  - The aging brain undergoes a process of enhanced peroxidative stress, as shown by
      reports of altered membrane lipids, oxidized proteins, and damaged DNA. The aims
      of this review are to examine: (1) the possible contribution of mitochondrial
      processes to the formation and release of reactive oxygen species (ROS) in the
      aging brain; and (2) the age-related changes of antioxidant defenses, both
      enzymatic and nonenzymatic. It will focus on studies investigating the role of
      the electron transfer chain as the site of ROS formation in brain aging and the
      alterations of the glutathione system, also in relation to the effects of
      exogenous pro-oxidant agents. The possible role of peroxidative stress in age
      related neurodegenerative diseases will also be discussed.

PMID- 7635360
TI  - N-methyl(R)salsolinol produces hydroxyl radicals: involvement to neurotoxicity.
AB  - Recently, (R)-1,2-dimethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline [N-methyl
      (R)salsolinol, NM(R)Sal] and 1,2-dimethyl-6,7-dihydroxyisoquinolinium ion
      [DiMeDHIQ+] were found to cause a syndrome similar to parkinsonism in rodents.
      NM(R)Sal is produced in the brain by N-methylation of a naturally occurring
      catechol isoquinoline, 1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline
      [(R)salsolinol, (R)Sal], which is formed from dopamine. The mechanism of NM(R)Sal
      cytotoxicity to dopamine neurons was examined using in vitro experiments.
      NM(R)Sal was found to be nonenzymatically oxidized into DiMeDHIQ+, with
      concomitant formation of hydroxyl radicals. The oxidation and the radical
      production were completely inhibited by the antioxidants, ascorbic acid and
      reduced glutathione, and the radical formation was enhanced by Fe(II) and, to a
      less extent, by Fe(III). The oxidation of NM(R)Sal into DiMeDHIQ+ and the
      production of hydroxyl radicals may be essential for neurotoxicity to develop in
      dopamine neurons. The possible involvement of this catechol isoquinoline in the
      pathogenesis of Parkinson's disease is discussed.

PMID- 7635362
TI  - The level of human decidua-associated protein hDP-200, in uterine fluid and
      serum.
AB  - Prospective uterine fluid sampling in 140 patients was performed using a Wallace
      catheter. The levels of human decidua-associated protein (hDP)-200 in the uterine
      fluid and in the serum, and the total protein concentration in the uterine fluid
      were determined. Uterine fluid volumes were scored during the hysteroscopy and no
      correlation was found with the phase of the menstrual cycle. The total protein
      concentration in the uterine fluid did not vary significantly during the
      menstrual cycle. The hDP-200 levels in uterine fluid were significantly higher
      than those in the serum, although considerable individual variation in the level
      of uterine fluid hDP-200 was found.

PMID- 7635363
TI  - Endothelin-1 levels in the maternal-fetal dyad.
AB  - The aim of this study was to determine the distribution of ET-1 levels in the
      term maternal-fetal dyad. We also compared the levels of ET-1 between umbilical
      vessels and assessed the effect of labor on the concentration of ET-1. The ET-1
      levels were measured in plasma from 18 term maternal-infant pairs. Amniotic fluid
      ET-1 levels were also measured in 9 of these pregnancies. The ET-1 levels were
      determined by radioimmunoassay (RIA) after extraction of plasma using Sep-Pak C18
      cartridges. There were no significant differences in the ET-1 levels between the
      umbilical artery and vein. However, there were significant differences in the
      umbilical artery concentration in women who labored when compared with those
      delivered without labor (6.0 +/- 1.1 vs. 2.7 +/- 0.7 pg/ml; t test, p = 0.022).
      ET-1 levels were lowest in the maternal plasma (0.9 +/- 0.2 pg/ml) and highest in
      the amniotic fluid (83 +/- 15 pg/ml). Assuming that elevated plasma ET-1 levels
      reflect increased bioactivity, the higher mean ET-1 levels in the cord vessels
      and in the amniotic fluid when compared to maternal levels suggest a role for ET
      1 in the regulation of the fetoplacental circulation and in the constriction of
      blood vessels in the uterus after parturition. The higher levels of ET-1 in the
      umbilical artery of women who underwent labor implies that ET-1 is released as a
      result of the stress of labor.

PMID- 7635364
TI  - Fallopian tube sperm perfusion has no advantage over intra-uterine insemination
      when used in combination with ovarian stimulation for the treatment of
      unexplained infertility.
AB  - In this prospective randomized study we treated 60 couples with unexplained
      infertility with a combination of ovarian stimulation and either intrauterine
      insemination (IUI) or fallopian sperm perfusion (FSP). In the IUI we used a
      volume of 0.5 ml of inseminate and in the FSP a volume of 4 ml. The demographic
      characteristics of the patients, the stimulation parameters and the sperm data
      were not statistically different between the two groups. The pregnancy rate per
      cycle was 16.2% in the IUI group and 14.5% in the FSP group and the pregnancy
      rate per woman was 40 and 36.7%, respectively (not statistically different). We
      conclude that IUI and FSP are equally effective in the treatment of couples with
      unexplained infertility.

PMID- 7635365
TI  - Change in atrial natriuretic peptide concentration after acute plasma volume
      expansion in normal pregnancy and preeclampsia.
AB  - Atrial natriuretic peptide (ANP) is found to be elevated in preeclamptic patients
      despite the presence of hemodynamic characteristics such as vasoconstriction and
      hypovolemia. In this study, the effect on ANP secretion of plasma volume
      expansion with crystalloid solutions was investigated. Seven preeclamptic and
      seven normotensive pregnant women in their last trimester were compared. After
      basal ANP measurements, 0.9% Ringer's solution, 15 cm3/kg body weight was infused
      within 30 min to expand the plasma volume. Blood sampling was repeated after the
      infusion. Maternal blood volume expansion was calculated from the decrease in
      hematocrit. Plasma ANP levels were corrected according to the degree of volume
      expansion. Basal mean levels in both groups were not different. Although the
      postinfusion levels of ANP in normotensive pregnant women were similar to the
      basal levels (means +/- SE: 20.6 +/- 0.41 and 27.2 +/- 0.52 pg/ml, respectively,
      p = 0.10), the postinfusion ANP levels in preeclamptic women increased
      significantly (21.4 +/- 0.31 and 34.1 +/- 0.28 pg/ml, respectively, p = 0.01).
      Preeclampsia is associated with a greater increase in plasma ANP levels in
      response to volume expansion compared with normotensive pregnancy. The greater
      change in the right atrial pressure with volume expansion, due to decreased
      compliance of the capacitance vessels in preeclamptic subjects might explain the
      greater change in the plasma level of ANP.

PMID- 7635366
TI  - Increased concentrations of lactate dehydrogenase in pregnancy with preeclampsia:
      a predictor for the birth of small-for-gestational-age infants.
AB  - Lactate dehydrogenase (LDH), alanine aminotransferase (ALT) and aspartate
      aminotransferase (AST) concentrations and platelet counts were measured in 26
      normal pregnant women and 51 preeclamptic women. In the normal-pregnancy group,
      no significant changes were found in the results of these tests. In the
      preeclampsia group, ALT and AST concentrations were not significantly higher than
      those in normal pregnancy, but the LDH concentrations increased and the platelet
      counts decreased significantly through the pregnancy. The increases in LDH did
      not correlate with changes in ALT or AST. Preeclamptic women with small-for
      gestational-age (SGA) infants had significantly higher LDH concentrations than
      those in the appropriate-for-gestational-age (AGA) group, but ALT and AST
      concentrations did not increase significantly. As reasons for the LDH increase in
      our subjects, liver damage was excluded and more active glycolysis in addition to
      severe cell damage due to chronic anoxemia were inferred. It is suggested that an
      increase in LDH is predictive of SGA infants in preeclamptic pregnancy,
      especially in those with normal liver function.

PMID- 7635367
TI  - Magnesium sulfate infusion during late gestation does not elicit a peripheral
      vascular steal and preserves placental perfusion.
AB  - Despite proven efficacy in interrupting uterine smooth muscle contraction for
      periods of 24-48 h, a recent clinical study concluded that the adrenergic beta
      receptor agonist, ritodrine hydrochloride (Yutopar) had significant detrimental
      side effects. Our previous preclinical studies have shown that ritodrine reduces
      placental blood flow via a vascular steal phenomenon. Moreover, ovarian blood
      flow is reduced by approximately 40% by ritodrine treatment. Reduced ovarian
      blood flow during tocolytic treatment presented the possibility for a blood-flow
      mediated decrease in progesterone secretion which would have negative effects on
      uterine quiescence. Pharmacological agents such as calcium channel blockers and
      magnesium sulfate have tocolytic potential. Magnesium sulfate infusion has a long
      clinical history of safety and efficacy; however, the possibility for latent
      detrimental hemodynamic and tissue/organ blood flow responses was unexamined.
      Therefore, the present studies examined hemodynamic and organ blood flow in near
      term pregnant rats given intravenous MgSO4. Our results show that (a) peripheral
      vascular steal is not induced, and (b) placental perfusion is preserved during
      MgSO4 infusion. However, ovarian blood flow is significantly reduced and blood
      flow mediated decrease in progesterone secretion requires consideration during
      implementation of tocolysis via MgSO4 infusion.

PMID- 7635368
TI  - A comparative study of vaginal misoprostol and intravenous oxytocin for induction
      of labour.
AB  - Fifty-two women who had labour induced by intravenous oxytocin were compared with
      404 women in whom labour was induced by vaginal misoprostol (50-150 micrograms).
      The induction-to-delivery intervals in the oxytocin and misoprostol groups,
      respectively, had the following durations. With Bishop's score < 6, 24.3 vs. 14.4
      h (p = 0.002), with Bishop's score > or = 6, 10.5 vs. 7.6 h (p = 0.02), with
      ruptured membranes, 8.8 vs. 8.5 h (p = 0.83), and with intact membranes, 19.6 vs.
      13.1 h (p = 0.005). The Caesarean delivery rate was 17.3% in the oxytocin group
      and 8.7% in the misoprostol group (p = 0.09). Maternal complications were few and
      drug side effects rare. It is concluded that vaginal misoprostol is a valuable
      and cost-effective alternative to intravenous oxytocin infusion for induction of
      labour.

PMID- 7635369
TI  - A randomized study comparing the efficacy of reducing the spontaneous abortion
      rate following lymphocyte immunotherapy and progesterone treatment versus
      progesterone alone in primary habitual aborters.
AB  - Presented herein is a randomized prospective study performed to evaluate the
      efficacy of the addition of lymphocyte immunotherapy (LI) to progesterone (P)
      therapy (LI/P) for the prevention of spontaneous abortion (SAB) in primary
      aborters with a history of three SABs. The incidence of intrauterine pregnancies
      in four cycles was 23 of 35 (65.7%) patients for LI/P vs. 14 of 31 (45.1%)
      patients treated with progesterone alone. SABs occurred in 6 of 23 (26.0%) LI/P
      treated patients compared to 8 of 14 (57.1%) given progesterone alone. The mean
      number of previous abortions in both groups was 3.9. The mean age of the LI/P
      group was 34.1 vs. 33.6 years for the group treated with progesterone alone.
      These data could be interpreted to show that progesterone therapy and LI
      independently inhibit SAB or that LI/P acts synergistically to inhibit immune
      destruction. LI/P therapy was found to be more effective than progesterone
      therapy alone.

PMID- 7635370
TI  - Oestrogen and progesterone receptors in normal human endometrium: comparison of
      immunocytochemical analysis on frozen and paraffin sections with or without
      enzymatic pretreatment.
AB  - Immunocytochemical study in paraffin sections of human endometrium showed that
      the receptor contents for both oestrogen and progesterone receptors were lower
      than in the frozen sections although the staining patterns were similar in these
      two section types. Pretreating the specimens with proteolytic enzymes like
      trypsin, DNase and pronase improved the oestrogen receptor staining but a better
      result with progesterone receptor staining was obtained when no enzymatic
      pretreatment was applied to the sections.

PMID- 7635371
TI  - Total serum calcium reference intervals in postmenopausal outpatients.
AB  - The distribution of values of serum calcium has been studied in the following
      four outpatient populations: premenopausal (n = 411) and postmenopausal women (n
      = 399), men less than 50 years old (n = 365) and men over 55 years old (n = 361).
      Their respective average total serum calcium values (mg/dl) were 9.42, 9.56,
      9.53, and 9.45. The reference intervals derived for total serum calcium (mg/dl)
      were 8.4-10.3 (premenopausal women), 8.4-10.7 (postmenopausal women), 8.6-10.5
      (men less than 50 years old), and 8.4-10.4 (men over 55 years old). Increased
      total serum calcium levels were observed in the postmenopausal women as compared
      with both premenopausal women (p < 0.001) and with men over 55 years old (p <
      0.003). Eight percent of the values obtained in postmenopausal women were above
      the current reference interval, as compared to 1.7% in premenopausal women, and
      3.3% in men over 55 years old. In conclusion, the age-related increase in total
      serum calcium in postmenopausal female outpatients warrants a higher upper limit
      of the reference interval for this subpopulation.

PMID- 7635372
TI  - Positive serology for chlamydia: is it always for Chlamydia trachomatis?
AB  - In this study we tried to determine the factual prevalence of Chlamydia
      trachomatis seropositive women. Sera of 174 sexually active women of reproductive
      age who attended the emergency room in our gynecology department were tested by
      both a species-specific solid-phase enzyme immunoassay (SPEIA, ImmunoComb,
      Orgenics, Israel) and by an immunoperoxidase assay (IPA). One-hundred and twenty
      two of 174 women (70.1%) tested were found positive for C. trachomatis by the IPA
      test. The SPEIA test identified 41 (33.6%) of those as positive for C.
      trachomatis and 81 (66.4%) positive for C. pneumoniae. We conclude that the
      currently used IPA method for chlamydia diagnosis overestimates C. trachomatis
      infection and its specificity for the diagnosis of C. trachomatis is limited. By
      using the SPEIA test, it is possible to distinguish between C. trachomatis and C.
      pneumoniae seropositivity.

PMID- 7635373
TI  - Infant with thanatophoric dwarfism in triplet pregnancy.
AB  - The case of a Japanese female infant with thanatophoric dwarfism, a triplet, is
      reported. The diagnosis was made at 18 weeks' gestation. Triplets were delivered
      at 30 weeks' gestation by cesarean section. Two infants, both males, were normal;
      the female with dwarfism died of respiratory distress 34 min after delivery. This
      is the first known case of one fraternal triplet being affected by thanatophoric
      dwarfism.

PMID- 7635374
TI  - Condyloma and cervical intraepithelial neoplasia of the endometrium.
AB  - Many studies have shown the presence of squamous metaplasia, dysplasia, carcinoma
      in situ and squamous cell carcinoma of the endometrium, whether they arose de
      novo or from direct extension from the cervix. Condyloma associated with squamous
      metaplasia or dysplasia of the endometrium is rare. We report a case of cervical
      intraepithelial neoplasia (CIN I) and condyloma of the endometrium. A 58-year-old
      woman presented with high-grade dysplasia on two successive pap smears. A total
      vaginal hysterectomy showed extensive CIN I and condyloma involving the entire
      endometrium. DNA in situ hybridization and polymerase chain reaction documented
      the presence of condyloma.

PMID- 7635375
TI  - [Effects of a vegetarian life style on health].
AB  - A vegetarian diet has a positive effect on various risk factors for coronary
      artery disease: these include usually lower average body weight, lower total and
      LDL cholesterol levels, and lower blood pressure. In conjunction with a generally
      more healthy way of life (more exercise, less alcohol and tobacco use),
      vegetarians have roughly 30% reduction in overall mortality. The prevalence of
      bronchial, colon and breast cancer is also lower. In particular in its strict
      form (total vegetarianism or veganism), a vegetarian regimen may lead to
      deficiency disorders, in particular vitamin B12 deficiency, which may occur
      especially in vegetarian children, pregnant or lactating women. Overall, however,
      a vegetarian regimen has a more beneficial effect on health than the usual
      Central European diet.

PMID- 7635376
TI  - [Nutrition and atherosclerosis].
AB  - Both the levels of fat and cholesterol in the diet and its fatty acid composition
      influence the CAD risk. In recent years, it has been recognized, however, that a
      high percentage of polyunsaturated fatty acids can have a negative effect, for
      example on the immune system. It is therefore recommended that 7-10% of dietary
      energy be consumed in the form of polyunsaturated and saturated fatty acids, but
      10-15% as mono-unsaturated fatty acids. In view of the associated favorable
      effect on CAD mortality, an increase in consumption of sea fish can now be
      recommended, while the benefits of consuming high doses of fish oil has not been
      proven. The positive effect of a fiber-rich diet is largely due to the associated
      decrease in consumption of saturated fatty acids. An additional cholesterol
      lowering effect has been demonstrated only for particular substances, for example
      oat bran. Numerous other dietary constituents, such as alcohol, salt or
      antioxidants, may also have effects on atherogenesis.

PMID- 7635377
TI  - [Responsibilities and value of autopsy. The physician's responsibility for
      disclosure of iatrogenic damage--3].

PMID- 7635378
TI  - [Fungal diseases of the skin (dermatomycoses). 1: Dermatomycoses of the feet].

PMID- 7635379
TI  - [Ebola virus and hemorrhagic fever--still a mysterious disease. Pathogens are
      endemic in tropical Africa--humans and monkeys are apparently only secondary
      hosts].

PMID- 7635380
TI  - [Chronic diarrhea: difficulties in determining the etiology. Diagnosis from
      irritable bowel syndrome to AIDS].

PMID- 7635381
TI  - [Only low NO concentrations enhance myocyte contraction. Direct effect in heart
      muscle cells is determined].

PMID- 7635383
TI  - [Purulent meningoencephalitis--studies of disease progression and prognosis].
AB  - The course of acute purulent meningitis and meningocephalitis was investigated in
      101 patients using records and a questionnaire directed to all patients. Patients
      who survived meningoencephalitis were asked to come to a neurological
      examination. Neuropsychological status, EEG and Tc-HMPAO-Spect were also
      performed in these patients. The patients were treated with a combination of
      three antimicrobial agents which was commonly used at our hospital during the
      investigation time consisting of penicillin, a cephalosporine of the third
      generation and an aminoglycoside. 40% of the patients suffered from more or less
      severe neurologic sequelae; remaining cognitive deficits were also frequent. On
      the whole there was a tendency towards improvement in patients who suffered from
      less severe deficits at the time of discharge from hospital, patients with more
      severe deficits also showed slight improvement but generally did not reach a
      restitutio ad integrum. Regarding this, in our opinion a broad initial
      antimicrobial therapy should be used, although a statistically significant
      improvement of the patient's outcome by this could not be shown. Lethality as
      well as the frequency of complications do not seem to differ over many years
      although antimicrobial and intensive care treatment were improved. Thus, the
      outcome seems to depend largely on the occurrence of secondary focal
      complications or brain oedema.

PMID- 7635382
TI  - [Ignatius of Loyola--gifted or mentally ill?].
AB  - Subsequent to a severe injury and under the influence of religious reading,
      Loyola experienced a dramatic mental change in his spiritual values in the sense
      of a sublimation to an alternative knighthood. His behaviour patterns observed
      thereafter were determined by a totality of his attachment to God. Based on this
      certainty in his faith, which was free from any doubts, and on God, and with the
      background of fasting and praying, he had visionary and pseudo-hallucinatory
      experiences. As the founder of an order and head of the community of Jesuits,
      Ignatius of Loyola proved to be diplomatically highly talented. There is no
      evidence of any psychotic disease. Also, there is no probability of a personality
      disorder in the sense of a neurosis. The numerous unusual behaviour patterns of
      Ignatius cannot be interpreted as psychopathological symptoms. It is justified to
      call him a genius.

PMID- 7635384
TI  - [Psychiatric diagnosis in general practice. ICD 10-Primary Health Care].
AB  - Along with Chapter V (F) of ICD-10 (International Classification of Diseases,
      10th Revision) the WHO (World Health Organisation) developed a number of
      diagnostic instruments for different purposes. The ICD-10-PHC (Primary Health
      Care) is a short classification system which is to be used in general practice
      and primary health care. This system is tested in a worldwide field trial. The
      ICD-10-PHC and the study design in German-speaking countries are described in the
      following paper. First results of the field trial in Lubeck show that the OFFeral
      conception of the system was assessed useful (72%). The ease of the diagnostic
      process was assessed "easy" (30.4%) or "moderate" (47.6%). Between 23% and 34% of
      the participants of the field trial had proposals for changes. The results show
      that the ICD-10-PHC can hopefully lead to better standards in the treatment of
      psychiatric patients in primary care.

PMID- 7635385
TI  - [Hebephrenic symptoms as an expression of an XYY chromosome abnormality? Case
      report of a patient with suspected sexual abuse of his own 2 minor children].
AB  - A 48 year old patient was hospitalised because of parasuicidal behaviour and
      suicidal ideation. He was under suspicion of having sexually abused his 4-year
      old daughter and his 4-year old son. At the age of 17, he was hospitalised in a
      psychiatric ward under the diagnosis of hebephrenic schizophrenia. He
      successfully received an insulin coma therapy. Because of his increased height
      (1.89 m), mental retardation and other psychical disorders in his youth, we now
      suspected him of having an extra Y chromosome which was confirmed by chromosome
      analysis. The non-uniform symptomatology of XYY-individuals includes a
      hebephrenic aspect. Concerning the different therapeutical and juridical
      consequences, we considered a critical investigation of the former diagnosis
      "Hebephrenic Schizophrenia".

PMID- 7635387
TI  - [Akinetic mutism in decompensated triventricular hydrocephalus].
AB  - The case of a 21-year-old man with obstructive hydrocephalus who suffered
      multiple shunt failures is presented. The patient developed a syndrome of
      akinetic mutism that improved after administration of bromocriptine and
      metoprolol.

PMID- 7635388
TI  - [Diagnosis and therapy of obsessive-compulsive disorders].

PMID- 7635386
TI  - [The neurobiology of alcoholism. Neuropathology and CT/NMR findings].
AB  - The authors deal with the heuristic value of the "neurobiological model of
      alcohol dependence". It allows the study of the influence of a defined noxe on
      different brain structures. Additionally, it enables the quantification of
      regeneration and restitution processes in abstinence. Because of this, the
      alcoholism model goes beyond dementia, the model which has dominated brain
      research so far. Neuropathological studies in humans and animals found a
      reduction in the volume of white matter and a partial degeneration, or even loss
      of specific neurons. According to animal data, this could to a certain extent be
      genetically determined. Alcohol exerts a distinct influence on different
      neurotransmitter systems. This research will deepen our understanding of the
      neurotoxic and psychotropic properties of alcohol, and of the development of
      dependence. Little is known about the role of astrocytes in the reaction of the
      brain to alcohol. Here again, the neurobiological model of alcohol dependence
      could be of value in learning more about their interactions with neurons. Using
      Magnetic Resonance Imaging and CAT-scans, the decrease in volume of white and
      grey matter was demonstrated in vivo. The degree and the time course of brain
      damage seems to be influenced less by drinking history than by age and gender.
      There is evidence that female alcoholics develop brain damage more readily than
      men. When abstinent, an increase in the volume of white and grey matter can be
      observed. This is not due to the rehydration of brain tissue alone. Future
      research will need to deal with the question of whether the central nervous
      system is capable of partial regeneration. For the study of neuroplasticity, the
      neurobiological model of alcohol dependence seems to be particularly well suited.

PMID- 7635389
TI  - [Ambulatory behavior therapy in obsessive-compulsive disorders].
AB  - The term Obsessive Compulsive Disorder (OCD) is a label for a variety of
      syndromes with changing symptom configurations and different intraindividual as
      well as interactional functions. They are among the most difficult to treat
      psychiatric disorders. Heterogeneous variables affecting personal development in
      family, school, and peer-group, as well as genetic or brain organic variables
      contribute to the development of obsessions and compulsions. In more than 50% of
      patients with OCD we find one or more of the following disturbances before the
      outbreak of the disorder: low self-esteem; social deficits; increased anxiety
      level with increased, latent aggressiveness; striving for 100% security.
      Behaviour therapy today is the "treatment of choice" for OCD--both in respect of
      direct symptom reduction as well as the treatment of "causes", co-morbidity and
      risk factors. Additionally to the use of highly standardised "symptom techniques"
      individualized, multimodal treatment is necessary in the more severely disturbed
      patients. Long-term follow-up results show 50-80% success--probably depending on
      variations in the study samples regarding the type of obsessions and compulsions,
      the degree of developmental deficits before the occurrence of OCD, actual co
      morbidity, and professional as well as private life conditions. Whether and to
      what degree additional psychotropic medication can enhance the efficacy of
      behaviour therapy, and whether the high relapse rates of 70% after
      discontinuation of previously successful drug treatment can be reduced by
      concomitant or subsequent behaviour therapy, cannot be safely concluded from the
      currently available studies. Are the non-responders in each of these treatments
      the responders of the non-responders in the alternative treatment mode?

PMID- 7635390
TI  - [Obsessive-compulsive disorders--inpatient behavior therapy].
AB  - Exposure therapy with response prevention is regarded as the most effective
      treatment in obsessive compulsive disorder. This procedure has been applied in
      outpatients as well as inpatients.

PMID- 7635391
TI  - [Trends in drug therapy of obsessive-compulsive disorders].
AB  - Within different drug treatment strategies in obsessive-compulsive disorder (OCD)
      namely selective serotonin reuptake inhibitors (SSRI) (e.g. Fluoxetine max. 60
      mg/die as well as Clomipramin 200 mg/die) have conveyed consistent benefit. In
      the case of non-response after an adequate treatment of 10-12 weeks it should be
      switched on alternative serotonergic antidepressants. If a persistent non
      response results a so-called "augmentation treatment" is recommended. The
      principle of augmentation consists in an increase of activity resulting from
      combination of serotonin agonists (e.g. Buspiron) with SSRIs. The combination of
      monoaminoxidase inhibitors (MAOI) with SSRIs--in the literature often described
      as effective in treatment resistant OCD--is inadvisable and strictly contra
      indicated (cave: Serotonin-Syndrome). In some cases monotherapy with MAOI seems
      effective (Schmauss et al., 1993). For this, it has to be regarded that a
      restriction period is given (e.g. 5 weeks after a pre-going Fluoxetine
      treatment). The combination of SSRIs and alternative serotonergic antidepressants
      with neuroleptics is only effective in cases of "spectrum disorders" and
      comorbidity (namely Gilles-de-la-Tourette-Syndrom). The use of neuroleptics in
      OCD should be strictly limited.

PMID- 7635392
TI  - [Drug treatment of obsessive-compulsive disorders--a comparative study of the
      effectiveness of clomipramine and fluoxetine].

PMID- 7635393
TI  - [The role of serotonin in behavior modulation].
AB  - The central projection systems represent an expansive and important component of
      the brainstem reticular core which provide modulatory input into multiple target
      networks throughout the entire vertebrate neuraxis. Most of the afferent input
      into the cranial raphe originates within sensory uni- and polymodal, associative
      and limbic cortices suggesting that serotonin modulates preprocessed information.
      The serotonergic neurons discharge in a remarkably stable and tonic fashion
      during wakefulness. Some 5-HT neurons increase their discharge rate phasically in
      association with the activation of central rhythmic pattern generators involved
      in consummatory and grooming behaviour. In concert with enhancing motor
      functions, the serotonergic systems discretely deamplify sensory attentiveness
      and pain processing, thereby establishing an essential and protective filter
      mechanism against distracting and irritating noise effects of sensory afferent
      input level. In addition, serotonin restrains the latency to responding, i.e.
      impulsivity. These effects of serotonin are mediated by multiple receptor
      subtypes with distinct pre- and postsynaptic localisation and regional
      distribution pattern, acting via amplifying (5-HT2 receptors) or desamplifying (5
      HT1 receptors) G-protein-dependent transduction mechanisms. The breakdown of
      these protective and adaptive functions of 5-HT in complex behaviour and in basic
      aspects of sensorimotor integration may have a pathogenetic role in disorders of
      impulse control (e.g. bulimia nervosa and OCD) which have been found to respond
      to high-dose, long-term treatment with selective serotonin reuptake inhibitors.

PMID- 7635394
TI  - [Psychiatric diagnosis, differential diagnosis and differential therapy of
      obsessive compulsive-disorders].

PMID- 7635395
TI  - A nurse's diary.

PMID- 7635396
TI  - Notes from the school.

PMID- 7635397
TI  - My courier experience.

PMID- 7635398
TI  - Reflections on the journey to CNEP.

PMID- 7635399
TI  - Sympatho-adrenergic activation of the ischemic myocardium and its arrhythmogenic
      impact.
AB  - Increased sympathetic activity has been documented in patients during acute
      myocardial infarction. Clinical and experimental studies have suggested that this
      increased sympatho-adrenergic activation may contribute to the development of
      lethal ventricular arrhythmias in the ischemic heart. In acute myocardial
      ischemia, adrenergic stimulation of the ischemic myocardium is independent of
      plasma catecholamines, since local catecholamine concentrations within the
      ischemic myocardium surpass plasma concentrations by several orders of magnitude.
      Both afferent and efferent autonomic nerves are activated immediately with
      myocardial ischemia. Poorly perfused myocardium, however, is protected within the
      first few minutes of ischemia, via several mechanisms, against high local
      concentrations of catecholamines. Ischemia-associated metabolic alterations, such
      as extracellular potassium accumulation, acidosis, and especially the
      accumulation of adenosine reduce the transmitter release induced by central
      sympathetic stimulation. Furthermore, the functional neuronal amine reuptake
      (uptake1) prevents excessive local accumulation of noradrenaline. With
      progression of myocardial ischemia to more than 10 min local nonexocytotic
      noradrenaline release prevails. This release is not prevented by the above
      mentioned protective mechanisms and accounts for local extracellular
      catecholamine concentrations in the micromolar range, i.e., 100 to 1000 times
      higher than the normal plasma concentrations. It shows several features that make
      it possible to differentiate it from exocytotic release and to assign it to a
      carrier-mediated transport of noradrenaline from the sympathetic nerve ending
      into the synaptic cleft. This release is independent of central sympathetic
      activity, availability of extracellular calcium, activation of both neuronal
      calcium channels and protein kinase C, and is not accompanied by the release of
      sympathetic co-transmitters such as neuropeptide Y. It is however suppressed by
      blockers of uptake1 and by inhibitors of sodium-proton exchange. Depletion of
      cardiac catecholamine stores by chronic sympathetic denervation effectively
      suppresses malignant arrhythmias induced by experimental coronary ligature.
      Accordingly, inhibitors of nonexocytotic noradrenaline release such as uptake1,
      blocking agents or sodium-proton exchange inhibitors effectively reduce the
      occurrence of ischemia-associated ventricular fibrillation, emphasizing the
      relevance of nonexocytotic noradrenaline release in myocardial ischemia. At the
      postsynaptic side, catecholamines released during myocardial ischemia exert their
      effects by stimulating alpha- and beta-adrenergic receptors of cardiac myocytes.
      During acute myocardial ischemia the responsiveness of adrenergic receptors to
      stimulation by catecholamines is enhanced. Several studies have demonstrated an
      increase in functionally coupled beta-adrenergic receptor number during
      myocardial ischemia. Likewise, alpha 1-adrenergic responsivity increases in
      myocardium subjected to acute ischemia and contributes significantly to the
      arrhythmogenic effect of catecholamines.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7635400
TI  - Clinical evidence for the fatal interaction of ventricular tachyarrhythmias,
      myocardial ischemia and sudden cardiac death.
AB  - During recent years, experimental data have collected convincing evidence for the
      fatal interaction of myocardial ischemia, ventricular tachyarrhythmias, and
      sudden cardiac death. In the clinical setting, data reporting on the daily
      relevance of such a fatal interaction lacked until recently. However, there is
      now increasing evidence from autoptic studies, from the evaluation of patients
      who survived one episode of sudden cardiac death, from the follow-up of these
      patients when treated or not by revascularization therapy and/or an implantable
      cardioverter-defibrillator and, most recently, from studies in patients with
      stable and especially unstable angina pectoris suffering from Holter-documented
      ischemic proarrhythmia, that acute and transient myocardial ischemia play an
      important role for the initiation as well as the aggravation of ventricular
      tachyarrhythmias and out-of-hospital sudden cardiac death. The present work is
      directed to summarize our clinical knowledge on this topic and to indicate that
      preventive strategies for myocardial ischemia are the "antiarrhythmic" of choice
      in patients with severe coronary artery disease and evidence for ischemic
      proarrhythmia.

PMID- 7635401
TI  - Risk stratification and prediction of sudden death following myocardial
      infarction.
AB  - Accurate and reliable identification of those survivors of acute myocardial
      infarction who are at high risk of sudden death remain an important and
      challenging problem. This review summarises the current state-of-the-art of the
      risk stratification techniques and lists achievements in this field. The review
      comments in detail on individual factors used in risk stratification. Residual
      ischemia may be considered as one of the main triggering factors of post
      infarction arrhythmia. Depressed left ventricular ejection fraction indicates
      deterioration of ventricular function. Electrical instability of the myocardium
      reflects the potential substrate of arrhythmia. Frequent ventricular ectopic
      activity provides triggers of ventricular tachycardia and/or fibrillation when
      acting on a suitable substrate. Impaired autonomic status of the heart may lead
      to the loss of vagal antiarrhythmic protection. Further, the tests used for risk
      stratification are discussed. Ventriculography provides estimates of left
      ventricular ejection fraction. Holter monitoring is used for the assessment of
      ventricular ectopic activity and heart rate variability. Exercise testing is used
      to address residual ischemia. Programmed ventricular stimulation and the analysis
      of signal averaged electrocardiograms estimate electrical instability of the
      myocardium. Baroreflex sensitivity is a measure of cardiac parasympathetic
      reflexes. The design and results of different experimental and clinical studies
      which utilised these tests are also discussed.

PMID- 7635402
TI  - Therapeutic consequences of newer studies addressing the problem of myocardial
      ischemia and ventricular arrhythmias.
AB  - Direct evidence from pathologic-anatomical studies in victims of sudden cardiac
      death has been given for acute ischemia (caused by either an acute thrombus,
      plaque fissuring or an organizing thrombus) to play a major role in the genesis
      of sudden cardiac death. Furthermore, indirect data on the effects of drugs in
      the setting of acute myocardial infarction have demonstrated that treating
      patients with beta-blocking agents is more beneficial than treating them with a
      pure anti-arrhythmic drug such as lidocaine. Whereas lidocaine, which also
      reduces the incidence of ventricular fibrillation in the setting of acute
      myocardial infarction, may produce an excess of mortality, beta-blockers reduce
      ventricular fibrillation and are associated with a prolonged survival. Further,
      indirect evidence on the role of ischemia in ventricular arrhythmias is given in
      patients with chronic ischemic heart disease by several studies on coronary
      revascularization and by studies on antiarrhythmic drugs versus beta-blockers in
      the same situation. In conclusion, there is clear evidence from studies of
      coronary revascularization and from studies on drug intervention in different
      patient populations with ischemic heart disease at risk for ventricular
      arrhythmias and/or for sudden cardiac death that ischemia plays an important role
      in the genesis of these arrhythmias.

PMID- 7635403
TI  - [Stent after-care: new approaches to coagulation inhibiting therapy].

PMID- 7635404
TI  - Evidence for spontaneous immunosuppression in autoimmune hepatitis.
AB  - Autoimmune hepatitis (AIH) runs a variable clinical course. Slow disease
      progression or even spontaneous remissions can be observed and suggest that the
      autoimmune process can, at least to a certain extent, be controlled by regulatory
      elements of the patient's own immune system. In experimental autoimmune hepatitis
      (EAH) spontaneous recovery is regularly observed and associated with antigen
      specific and antigen-nonspecific suppression. The aim of the current study was to
      search for similar immunoregulatory phenomena in patients with AIH. We examined T
      cell reactivity to soluble human liver antigens in 11 patients with active
      autoimmune hepatitis and 30 patients with other liver diseases (chronic viral
      hepatitis, primary biliary cirrhosis, fatty liver). T-cell reactivity to liver
      antigens was almost exclusively confined to the AIH patients. In 9 of these 11
      patients we were able to compare the T-cell response in active untreated disease,
      directly after initiation of immunosuppressive therapy and in remission, at which
      point T-cell reactivity was found to be markedly reduced. Addition of irradiated
      peripheral blood cells from the active disease phase or the remission phase to
      the responding cells taken before treatment showed that in eight of the nine
      patients there was marked suppression of the liver-specific T-cell response by
      cells from the remission phase. Study of the in vivo immune responsiveness by
      giving a tetanus toxoid booster immunization to nine patients with active
      untreated AIH as well as healthy controls and patients with other liver diseases
      showed that none of the patients with AIH showed a response to the tetanus
      immunization, whereas almost all the other patients showed marked
      responses.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7635405
TI  - Focal lymphocytic aggregates in chronic hepatitis C: occurrence,
      immunohistochemical characterization, and relation to markers of autoimmunity.
AB  - Intrahepatic lymphocytic aggregates are observed in chronic hepatitis C as well
      as in autoimmune chronic hepatitis. Autoantibodies and autoimmune manifestations
      may occur in hepatitis C. It has been suggested that the lymphocytic aggregates
      play a role in the liver injury of chronic hepatitis C by an immune-mediated
      mechanism. We studied the occurrence of intrahepatic lymphocytic aggregates and
      of autoantibodies in a consecutive series of 128 patients with chronic hepatitis
      C. For the phenotypic characterization of the lymphocytic aggregates cryostat
      sections and microwaved paraffin embedded sections were immunostained with
      monoclonal antibodies directed against T cell subsets, B cells, killer/natural
      killer cells, follicular dendritic cells, and macrophages. Autoantibodies were
      tested by immunofluorescence (antinuclear, anti-smooth muscle, antimitochondrial)
      and by enzyme-linked immunosorbent assay (anti-soluble liver antigen, anti
      liver/kidney microsome, anti-human receptor for asialoglycoprotein). Focal
      lymphocytic aggregates in portal tracts were observed in 76 of 128 (59%)
      patients. The cellular composition of the aggregates was constant: a core of B
      cells mixed with many T helper/inducer lymphocytes, and an outer ring was
      prominently formed by T suppressor/cytotoxic lymphocytes. A germinal center was
      rarely identifiable. The presence of lymphocytic aggregates was inversely
      correlated with the degree of fibrosis. Lymphocytic aggregates appeared more
      frequently in chronic persistent and chronic active hepatitis in comparison with
      cirrhosis and in the presence of bile duct damage. No correlation was found
      between lymphocytic aggregates and autoantibodies or other markers of
      autoimmunity. The lymphocytic aggregates are frequent in chronic hepatitis C.
      Their cellular composition is similar to that of primary lymphoid follicles in
      lymph nodes. Their presence does not seem to be correlated with features of
      autoimmunity.

PMID- 7635406
TI  - Mouse hepatitis virus type 3 infection provokes a decrease in the number of
      sinusoidal endothelial cell fenestrae both in vivo and in vitro.
AB  - Fenestrations of hepatic endothelial cells play an active role as a sieving
      barrier allowing extensive exchange between the blood and liver parenchyma.
      Alteration of these structures may be induced in the course of various
      pathological events and provoke important perturbations of liver function. We
      demonstrate here that sinusoidal endothelial cells are permissive for mouse
      hepatitis virus 3 (MHV3) in vivo and in vitro and that this infection leads to a
      striking decrease in the number of fenestrae. The disappearance of these
      structures observed under scanning electron microscopy or in cryofracture
      preparations in vivo and in vitro cannot be reversed by the action of
      cytochalasin B on the microfilament network. The decrease in the porosity seems
      to be related directly to the productive infection of the endothelial cells,
      because it was not observed in A/J mice resistant to the virus and in susceptible
      BALB/c mice immunized with a thermosensitive mutant in which no viral replication
      occurs. In conclusion, a viral infection of liver endothelial cells may cause
      extensive loss of the fenestrations and thus lead to important functional
      pertubations.

PMID- 7635407
TI  - Hepatitis C viral quasispecies in hepatitis C virus carriers with normal liver
      enzymes and patients with type C chronic liver disease.
AB  - Hepatitis C virus (HCV) has been reported to conform to a quasispecies nature,
      which is most evident in hypervariable regions of the putative envelope 2 domain.
      The aim of this study was to determine the relationship between the nucleotide
      complexity and diversity of hypervariable region 1 and various stages of the
      carrier states. The subjects studied were 20 HCV carriers with normal alanine
      aminotransferase (ALT) levels, 50 patients with chronic hepatitis who showed
      elevated ALT levels, 22 with cirrhosis, and 24 with hepatocellular carcinoma. The
      quasispecies complexity was analyzed by means of polymerase chain reaction
      mediated single strand conformation polymorphism (PCR-SSCP). The value of
      nucleotide diversity was calculated by PCR cloning and sequencing. The number of
      SSCP bands ranged from 1 to 7, with no significant differences in the mean
      numbers among the stages of HCV infection. There was no correlation between the
      amounts of serum HCV RNA and the numbers of SSCP bands. No significant difference
      was found in the values of nucleotide diversity between carriers with normal ALT
      levels (mean, 6.6 x 10(-2) per site) and patients with chronic hepatitis (7.7 x
      10(-2). These findings suggest that the quasispecies complexity of hypervariable
      region 1 is independent of the stage of chronic HCV infection.

PMID- 7635408
TI  - Does the healthy hepatitis C virus carrier state really exist? An analysis using
      polymerase chain reaction.
AB  - To determine whether the presence of hepatitis C virus (HCV) viremia correlates
      with the severity of liver disease in anti-HCV-positive apparently healthy blood
      donors, we studied 98 blood donors found positive for anti-HCV using enzyme
      linked immunosorbent assay (ELISA). Each subject underwent a liver biopsy, a test
      for HCV RNA in the serum by polymerase chain reaction (PCR), and a panel of liver
      injury tests. As a result, 97% of the anti-HCV-positive blood donors had some
      type of histological abnormality:22 (22%) had minimal changes, 1 (1%) had chronic
      lobular hepatitis, 40 (41%) had chronic persistent hepatitis (CPH), and 32 (33%)
      had chronic active hepatitis (CAH). Only 3 subjects had a normal liver histology.
      HCV RNA was detectable in the serum in 65% of the anti-HCV-positive donors. HCV
      RNA in serum was detectable in none of the donors with a normal liver histology,
      in 36% (confidence interval [CI], 17% to 59%) of those with minimal changes, in
      70% (CI, 53% to 83%) of those with CPH, and in 87% (CI, 71% to 96%) of those with
      CAH (P = .00001). HCV RNA was detectable in 75% of the donors with elevated (> 45
      U/L) alanine transaminase (ALT) values and in 59% of those with normal ALT levels
      (P = not significant). The incidence of chronic hepatitis was higher in HCV RNA
      positive than in HCV RNA-negative donors (88% vs. 50%; P = .00005).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7635409
TI  - Long-term decrease in serum N-terminal propeptide of type III procollagen in
      patients with chronic hepatitis C treated with interferon alfa.
AB  - To evaluate the effect of interferon alfa (IFN-alpha) on the hepatic
      extracellular matrix, we investigated the changes in serum N-terminal propeptide
      of type III procollagen during and after 4 months of INF-alpha treatment in 178
      treated and 45 nontreated patients with chronic hepatitis C. Serum pretreatment
      levels in nonresponders were significantly higher than those in long-term and
      short-term responders, but those levels were not different in the latter two
      groups. Serum propeptide levels decreased significantly during and after IFN
      alpha therapy in the treated patients, although those levels were unchanged in
      the nontreated patients. This decrease was sustained for 12 months after IFN
      alpha was completed not only in long-but also in short-term responders and
      nonresponders. Serum propeptide levels decreased in those with elevated
      pretreatment levels, but not in those with normal initial levels, whereas serum
      transaminase levels decreased similarly in both groups. The changes in serum
      propeptide levels during and after treatment were more closely correlated with
      the initial levels compared with those in serum transaminase levels. These
      results suggested that IFN-alpha treatment induces the long-term suppression of
      active fibrogenesis in chronic hepatitis C independent of antiviral and anti
      necroinflammatory effects, thus preventing progression to cirrhosis.

PMID- 7635410
TI  - Efficacy of screening donors for antibodies to the hepatitis C virus to prevent
      transfusion-associated hepatitis: final report of a prospective trial.
AB  - Routine screening of blood donors for anti-hepatitis C virus (HCV) has been
      implemented in most developed countries. However, the independent efficacy of
      such screening has not been established in a controlled, prospective study. We
      tracked 478 patients transfused with anti-HCV-negative blood by first-generation
      enzyme-linked immunoassay (EIA) between July 1989 and May 1990 and compared the
      incidence of transfusion-associated hepatitis and HCV infections with that found
      among 280 patients transfused with blood unscreened for anti-HCV during the
      immediately preceding year. Of the 280 patients who had received transfusions
      before donors were screened for anti-HCV, 27 (9.6%) developed posttransfusion
      hepatitis and 1 additional patient seroconverted to anti-HCV without evidence of
      hepatitis, for a risk of posttransfusion HCV infection of 10.7% (28 of 262
      recipients seronegative for anti-HCV before transfusion). Of the 478 patients
      transfused after July 1989 with blood screened for anti-HCV, only 9 (1.9%)
      developed posttransfusion hepatitis for a risk reduction of 80%. Seven of the 9
      residual cases of hepatitis were caused by HCV (7 of 456 recipients seronegative
      before transfusion or 1.5%) for a risk reduction of transfusion-associated HCV
      infection of 86%. In retrospect, an anti-HCV positive donor was detected by
      second-generation immunoassay in 4 (57%) of the 7 HCV cases from the study cohort
      and in 19 of the 23 (83%) cases from whom all donor samples were available for
      testing in the historical cohort. No additional infectious donors were detected
      by third-generation immunoassay or serum HCV-RNA by polymerase chain
      reaction.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7635411
TI  - Increased liver iron stores in patients with hepatocellular carcinoma developed
      on a noncirrhotic liver.
AB  - Iron was systematically studied in the nontumorous liver of 24 patients with
      hepatocellular carcinoma (HCC) developed on a noncirrhotic liver compared with 4
      control groups (cirrhosis with and without HCC, liver metastasis, and normal
      liver) matched according to age, sex, and presence of chronic alcoholism.
      Assessment of liver iron was made by (1) histology according to iron distribution
      and quantification (total iron score: 0 to 60), and (2) biochemistry (liver iron
      concentration-N < 36 mumol/g) with calculation of the hepatic iron index (liver
      iron concentration/age). Patients with hepatocellular carcinoma developed on a
      noncirrhotic liver presented with (1) histological iron in 83%; (2) parenchymal
      iron excess significantly more frequent (90%) than in controls; (3) total iron
      score (15 +/- 12) and liver iron concentration (81 +/- 96) significantly greater
      than in controls; and (4) hepatic iron index significantly increased (1.4 +/-
      1.5) when compared with control groups, except for the hepatocellular carcinoma
      complicating cirrhosis group (0.9 +/- 1.1). This study (1) shows a mild but
      unquestionable parenchymal iron excess in the nontumorous liver of most patients
      presenting with hepatocellular carcinoma developed on a noncirrhotic liver and,
      at a lesser extent, on cirrhosis, (2) should incite others to study the putative
      role of iron in the development of liver cancer both in patients with cirrhosis
      and those without it, whatever the cause of the underlying liver disease, and (3)
      add argument to take into account and to treat any liver iron excess, even when
      mild.

PMID- 7635412
TI  - Liver transplantation for sclerosing cholangitis.
AB  - The clinical course of 37 patients who underwent 46 liver transplantations for
      primary (n = 33) and secondary (n = 4) sclerosing cholangitis was reviewed. The
      median follow-up was 37 months. The patient and graft survivals for patients with
      primary sclerosing cholangitis at 1, 2, and 5 years were 96.9%, 91.6%, 87.9%, and
      83.1%, 74.2%, 65.2%, respectively. In the patients with primary sclerosing
      cholangitis (PSC), prior surgery except for simple cholecystectomy was associated
      with significantly greater operative time and blood loss. No cholangiocarcinoma
      was identified at the time of transplantation. Human leukocyte antigen typing for
      PSC patients was heavily weighed toward B8 (58.8%) compared with control (11.8%).
      Sixty-two percent of patients with PSC also had inflammatory bowel disease.
      Moderate or severe rejection requiring OKT3, "rescue therapy" with FK506, or
      retransplantation was relatively higher in patients with inflammatory bowel
      disease (70%) versus patients without inflammatory bowel disease (36.4%) and a
      matched control group (37.5%). Progressive inflammatory bowel disease was seen in
      6 of 19 patients, with 3 developing cancer and a dysplasia. Two patients in the
      entire group died of sepsis and 3 of colon cancer (2 recurrent and 1 primary).
      These data demonstrate that excellent survival results can be achieved in this
      group of patients. Rejection is frequent and often severe and steroid refractory.
      Colon cancer represents the most frequent cause of death in PSC patients after
      liver transplantation and demands constant attention.

PMID- 7635413
TI  - Hemodynamics after orthotopic liver transplantation: study of associated factors
      and long-term effects.
AB  - Among 68 liver transplant recipients, 190 hemodynamic studies were performed to
      evaluate the role of sepsis, anemia, acute graft rejection, and persistent
      portosystemic shunts. The hemodynamic outcome after orthotopic liver
      transplantation (OLT) in stable patients was also determined. Patients with
      sepsis showed a significant increase in cardiac index (5.1 +/- 0.9 vs. 3.4 +/-
      0.7 L/min m2) and hepatic venous pressure gradient (6.3 +/- 2.9 vs. 3.3 +/- 2.1
      mm Hg), compared with patients without sepsis. Cardiac index was higher in
      patients with, than in patients without, anemia (4.1 +/- 0.6 vs. 3.0 +/- 0.6
      L/min m2). The hepatic venous pressure gradient was higher in patients with than
      in patients without acute graft rejection (5.1 +/- 2.9 vs. 2.6 +/- 1.2 mm Hg).
      Among patients with acute rejection, the hepatic venous pressure gradient was
      higher in patients with severe rejection than in those with moderate or mild
      rejection (7.2 +/- 3.3 vs. 4.6 +/- 2.4 and 2.8 +/- 0.9 mm Hg). In the
      postoperative period, in patients undergoing transplantation for acute liver
      failure, the hepatic blood flow was normal and significantly lower than in
      patients receiving transplant for cirrhosis (1.15 +/- 0.37 vs. 1.96 +/- 0.71
      L/min). In patients undergoing transplantation for cirrhosis, cardiac index,
      azygos, and hepatic blood flows significantly decreased after 1 year compared
      with the first 6 postoperative months. Multivariate analysis showed that sepsis,
      anemia, and time after OLT were independent variables influencing cardiac index.
      Sepsis, time after OLT, and the existence of portosystemic shunts were
      independent variables influencing hepatic blood flow.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7635414
TI  - A prospective, randomized trial of sclerotherapy versus ligation in the
      management of bleeding esophageal varices.
AB  - We conducted a prospective, randomized trial comparing sclerotherapy and ligation
      in 120 patients with acute bleeding of esophageal varices. All the patients were
      cirrhotic, 59 received sclerotherapy, and 61 received ligation. Treatment was
      repeated regularly until the varices were obliterated. The mean follow-up period
      was 295 +/- 120 days and 310 +/- 105 days for the sclerotherapy and ligation
      groups, respectively. The control of active bleeding was 12/15 (80%) in the
      sclerotherapy group and 18/19 (94%) in the ligation group (P = .23). The numbers
      of treatment sessions required to achieve variceal obliteration were 6.5 +/- 1.2
      in the sclerotherapy group and 3.8 +/- 0.4 in the ligation group (P < .001).
      Recurrent bleeding from the gastrointestinal tract was 51% in the sclerotherapy
      group compared with 33% in the ligation group (P < .05). Recurrent bleeding from
      esophageal varices was 36% in the sclerotherapy group and 11% in the ligation
      group (P < .01). However, bleeding from ectopic varices and congestive
      gastropathy was less common in the sclerotherapy group (7%) than in the ligation
      group (18%) (P = .05). Significant complications were encountered in 19% of the
      sclerotherapy group and in 3.3% of the ligation group (P < .01). Comparison of
      Kaplan-Meier estimates of time to death of both groups showed a significantly
      lower mortality in the ligation group (P = .011). Both sclerotherapy and ligation
      can effectively arrest active bleeding from esophageal varices. However, ligation
      is more effective than sclerotherapy in decreasing the risk of rebleeding from
      esophageal varices with fewer complications. Ligation can also achieve
      obliteration of esophageal varices more rapidly than sclerotherapy.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7635415
TI  - Decreased right heart blood volume determined by magnetic resonance imaging:
      evidence of central underfilling in cirrhosis.
AB  - Whether the central blood volume is reduced or expanded in cirrhosis is still
      under debate. Accordingly, the current study was undertaken to assess the volume
      of the heart cavities. Ten cirrhotic patients and matched controls had their
      right and left ventricular end-diastolic volumes (RVDV and LVDV), and end
      systolic volumes (RVSV and LVSV) determined by magnetic resonance imaging (MRI).
      RVDV (122 vs. control 166 mL, P < .02), RVSV (41 vs. 80 mL, P < .02) and right
      atrial volume (47 vs. 64 mL, P < .05) were significantly reduced in the patients.
      In contrast, LVDV (134 vs. 129 mL, NS), LVSV (54 vs. 40 mL, NS), and left atrial
      volume (70 vs. 57 mL, P = .08) were normal or slightly increased. The right
      ejection fraction (68% vs. 53%, P < .05) was significantly increased, but the
      left ejection fraction was slightly reduced (61% vs. 69%, NS). The central and
      arterial blood volume (CBV), assessed as the cardiac output (CO) multiplied by
      the central circulation time, was significantly decreased (1.47 vs. 1.81 L, P <
      .05). The noncentral blood volume (4.43 vs. 3.64 L, P < .02), plasma volume (4.05
      vs. 3.27 L, P < .02), and CO (7.11 vs. control 5.22 L/min, P < .01) were
      significantly increased in the patients. CCT (13.1 vs. 20.0 sec, P < .005) and
      the right ventricular transit time (0.79 vs. 1.35 sec, P < .005) were
      significantly reduced, but the left ventricular transit time was normal (0.91 vs.
      0.88 sec, NS). Systemic vascular resistance was reduced (991 vs. 1,490
      dyn.sec/cm5, P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7635416
TI  - Effect of upright posture and physical exercise on endogenous neurohormonal
      systems in cirrhotic patients with sodium retention and normal supine plasma
      renin, aldosterone, and norepinephrine levels.
AB  - It is well known that sodium retention occurs in a significant proportion of
      patients with cirrhosis despite normal supine plasma levels of renin, aldosterone
      (ALDO), and norepinephrine (NE). The current study was performed to assess
      whether this subset of patients also present normal activity of the renin
      aldosterone and sympathetic nervous systems during upright posture in sitting
      position and moderate physical exercise. Nine healthy controls, 14 patients with
      compensated cirrhosis and 10 patients with cirrhosis, ascites, sodium retention,
      and normal supine plasma renin activity (PRA) and ALDO and NE concentration were
      sequentially studied after 60 minutes in supine rest, 30 minutes in sitting
      position, and 30 minutes of cycloergometric exercise (3-METs). Sitting position
      and exercise were associated with similar stimulation of the renin-aldosterone
      and sympathetic nervous systems in the three groups of subjects. Consequently,
      cirrhotic patients with ascites showed values of PRA and plasma concentration of
      ALDO and NE similar to healthy subjects and patients with compensated cirrhosis
      during supine rest (renin: 1.4 +/- 0.3, 0.8 +/- 0.2, and 0.8 +/- 0.3 ng/mL;
      aldosterone: 24.3 +/- 4.7, 20.2 +/- 3.9 and 21.4 +/- 3.4 ng/dL; norepinephrine:
      252 +/- 23, 250 +/- 16, and 255 +/- 23 pg/mL), sitting position (renin: 2.1 +/-
      0.5, 1.1 +/- 0.3, and 1.6 +/- 0.4; aldosterone: 32.2 +/- 7.3, 23.7 +/- 5.3, and
      26.2 +/- 4.5; norepinephrine: 356 +/- 38, 401 +/- 63, and 420 +/- 35), and
      exercise (renin: 2.9 +/- 0.8, 1.6 +/- 0.4, and 2.2 +/- 0.5; aldosterone: 43 +/-
      6.4, 34.9 +/- 8.5, and 38.2 +/- 5.3; norepinephrine: 481 +/- 35, 499 +/- 54, and
      534 +/- 48).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7635417
TI  - Calcium carbonate in cholesterol gallstones: polymorphism, distribution, and
      hypotheses about pathogenesis.
AB  - This study of sets of cholesterol gallstones collected consecutively from 222
      patients in La Paz, Bolivia, and Mexico City, Mexico, has developed a reliable
      infrared (IR) spectroscopic method for the detection of calcium carbonate in
      cholesterol gallstones and provided the basis for simultaneous identification of
      each of its three polymorphs: calcite, vaterite, and aragonite. The peaks in the
      854 to 876 cm-1 region demonstrated 98% sensitivity and specificity for carbonate
      detection. As little as 3% carbonate by weight could be detected using these
      peaks. The overall incidence of carbonate was 19% in these populations containing
      a high proportion of Amerinds. Infrared microspectroscopy of 10 to 50 microns
      particles, dissected from stones, allowed a ring-by-ring examination of 11
      carbonate-containing stones. It was determined that different carbonate
      polymorphs, when present in the same gallstone, almost always occurred in
      separate rings. In approximately half of the gallstones, different polymorphs
      were present in successive layers in the same stone, indicating that conditions
      governing stone growth changed cyclically. Carbonates were usually precipitated
      in peripheral layers rather than in the center, supporting the theory that
      formation of calcium carbonates may be related to episodes of intermittent
      obstruction of the cystic duct, as opposed to being a major factor in stone
      nidation.

PMID- 7635419
TI  - The liver in adolescents with alpha 1-antitrypsin deficiency.
AB  - Of 200,000 Swedish infants screened for alpha 1-antitrypsin deficiency (alpha 1
      ATD), 184 (127 PiZ, 2 PiZ-, 54 PiSZ, and 1 PiS-) children have been followed
      prospectively, of whom 1 PiSZ and 5 PiZ children died in early childhood. We now
      report clinical and biochemical signs of liver disease in adolescence and the
      prognosis of neonatal liver disease up to the age of 18 years. The alpha 1 ATD
      subjects were offered a clinical checkup and liver tests at 16 and 18 years of
      age, 150 of 178 alpha 1ATD subjects undergoing checkups at age 16 and 166 at age
      18. Liver tests were performed in 121 adolescents at both the 16- and 18-year
      checkups. None of the PiZ and PiSZ subjects checked at the age of 16 and 18 years
      had any clinical signs of liver disease. Abnormalities of serum alanine
      aminotransferase (S-ALAT) or gamma-glutamyl transferase (S-GT) were found at the
      16-year checkup (all PiZ and PiSZ subjects tested included) in 17% of PiZ and 8%
      of PiSZ adolescents, and at the age of 18 years in 12% of PiZ and 15% of PiSZ
      subjects. In only two cases were both S-ALAT and S-GT concentrations abnormal at
      both the 16-year and 18-year follow-ups. Serum procollagen III peptide
      concentrations were normal in all those with abnormal liver test results. Of 127
      PiZ subjects, 22 had manifested clinical signs of liver disease in infancy. Of
      these 22, two died early in life of cirrhosis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7635418
TI  - Peroxisome mosaicism in the livers of peroxisomal deficiency patients.
AB  - Peroxisomal deficiency disorders, which are genetically transmitted, are assumed
      to be expressed in all cells, and the use of cultured skin fibroblasts for
      diagnosis and research is based on this assumption. We describe three patients
      with clinical, biochemical, and microscopic evidence of a peroxisomal disorder.
      However, their liver displays mosaicism, i.e., parenchymal cells with peroxisomes
      are adjacent to cells without peroxisomes. Ten percent (volume), 8%, and less
      than 1% of the parenchyma possessed peroxisomes that can be identified in
      immunocytochemical tests for six matrix and membrane proteins performed by light
      and electron microscopy. In the bulk of the parenchyma, catalase is localized in
      the cytoplasm, and in such cells no peroxisomes are evident by electron
      microscopy and immunolabeling for the 43-kd peroxisomal membrane protein (PMP) in
      two patients; in the third case, peroxisomal membrane ghosts are present.
      Immunoblots of peroxisomal beta-oxidation enzymes show a pattern similar to that
      from patients with a generalized peroxisomal deficiency. In contrast to the
      clinical and biochemical signs of peroxisomal dysfunction and hepatic
      histopathology, cultured fibroblasts from two patients demonstrate normal
      peroxisomal functions, including very-long-chain fatty acid oxidation and
      plasmalogen synthesis.

PMID- 7635420
TI  - Synthesis of interleukin-1 beta in primary biliary cirrhosis: relationship to
      treatment with methotrexate or colchicine and disease progression.
AB  - Primary biliary cirrhosis (PBC) is a chronic, progressive, cholestatic liver
      disease. Interleukin-1 beta (IL-1 beta) may play a role in the pathogenesis of
      PBC by contributing to altered immune function and fibrosis. Colchicine or
      methotrexate has some beneficial effects in the treatment of PBC, and also
      affects interleukin-1 (IL-1). Therefore, we prospectively studied the synthesis
      of IL-1 beta by peripheral blood mononuclear cells (PBMC) from 42 patients with
      PBC entered into a randomized, double-blind, double-dummy controlled trial of
      colchicine and methotrexate. PBMC obtained at entry, 6, 12, 18, and 24 months
      were stimulated to produce IL-1 beta with phytohemagglutinin (PHA),
      lipopolysaccharide (LPS), Staphylococcus epidermidis, recombinant IL-2, or
      mitochondrial antigen. Patients in the two treatment groups did not differ at
      entry in biochemical measures or liver histological stage. Over 24 months in both
      groups, serum bilirubin and histologic stage remained stable and alkaline
      phosphatase decreased significantly. For all patients, synthesis of IL-1 beta
      increased constitutively and in response to immune-mediated stimulants (PHA, IL
      2, and mitochondrial antigen) but not the bacterial stimulants LPS or S
      epidermidis. Compared with levels of IL-1 beta at entry, PHA induced increases
      for patients treated with methotrexate (12, 18, and 24 months) or colchicine (18
      and 24 months). At 24 months, IL-2-induced IL-1 beta synthesis was increased in
      patients treated with methotrexate, whereas S epidermidis-induced IL-1 beta was
      enhanced in colchicine-treated patients. Before treatment, IL-1 beta production
      did not relate to severity of disease except in response to S
      epidermidis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7635421
TI  - Relationship between cardiomyopathy and liver disease in chronic alcoholism.
AB  - Based on anecdotal impressions, there is a common clinical perception that
      alcoholics with liver disease do not develop cardiomyopathy and that those with
      alcohol-induced cardiac disease are spared cirrhosis. To determine the
      relationship between alcoholic cardiomyopathy and cirrhosis, we carried out a
      prospective cross-sectional study that included: (1) 30 alcoholic men with
      cardiomyopathy; (2) 30 alcoholic men without cardiomyopathy (left ventricular
      ejection fraction > 55%); (3) 20 actively drinking alcoholics with cirrhosis; (4)
      15 abstaining alcoholics with cirrhosis; and (5) 15 nonalcoholics with cirrhosis
      of other etiologies. Cirrhosis was observed in 13 of 30 patients with alcoholic
      cardiomyopathy (43%), compared with 2 of 30 alcoholics without cardiomyopathy
      (6%) (P < .001). Ten of the 20 active alcoholics with cirrhosis (50%) showed
      evidence of dilated cardiomyopathy. Actively drinking alcoholics with cirrhosis
      had a significantly lower mean ejection fraction and shortening fraction, as well
      as a greater mean end-diastolic diameter and left ventricular mass than
      abstaining alcoholics with cirrhosis. Cardiac studies of patients with
      nonalcoholic cirrhosis were normal. We conclude that a positive correlation
      exists between alcoholic cardiomyopathy and cirrhosis. Alcoholics admitted solely
      for cardiomyopathy have a higher prevalence of cirrhosis than unselected
      alcoholics without heart disease. Actively drinking alcoholics admitted only for
      cirrhosis show impaired cardiac performance, whereas abstaining alcoholics with
      liver disease tend to manifest normal cardiac function.

PMID- 7635422
TI  - Protective effects of N-acetylcysteine on hypothermic ischemia-reperfusion injury
      of rat liver.
AB  - We investigated whether intraportal injection of 150 mg/kg N-acetylcysteine (NAC)
      into rats reduced hepatic ischemia-reperfusion injury after 48 hours of cold
      storage and 2 hours of reperfusion. The organ was isolated and perfused to
      evaluate liver function. The control group received an intraportal injection of
      5% dextrose. NAC increased L-cysteine concentrations 15 minutes after injection
      (1.29 +/- 0.11 mumol/g vs. 2.68 +/- 0.4 mumol/g, P < .05). However, neither
      treatment modified glutathione liver concentrations relative to preinjection
      values. After 48 hours of cold storage and 2 hours of reperfusion, livers from
      NAC-treated rats produced larger amounts of bile than those in the control group
      (5.04 +/- 1.92 vs. 0.72 +/- 0.37 microL/g liver; P < .05), and showed a
      significant reduction in liver injury, as indicated by reduced release of lactate
      dehydrogenase (679.4 +/- 174.4 vs. 1891.3 +/- 268.3 IU/L/g; P < .01), aspartate
      transaminase (AST) (13.94 +/- 3.5 vs. 38.75 IU/L/g; P < .01), alanine
      transaminase ALT) (14.92 +/- 4.09 vs. 45.91 +/- 10.58 IU/L/g; P < .05), and acid
      phosphatase, a marker of Kupffer cell injury (344.4 +/- 89.6 vs. 927.3 +/- 150.8
      IU/L/g; P < .01) in the perfusate. Reduced glutathione concentrations in the
      perfusate were similar in the two groups (805 +/- 69 vs. 798 +/- 252 nmol/L/g),
      whereas oxidized glutathione (GSSG) concentrations were higher in the control
      group (967 +/- 137 vs. 525 +/- 126 nmol/L/g; P < .05). Reduced glutathione (GSH)
      concentrations in liver tissue collected at the end of perfusion were
      significantly higher in the NAC group (7.3 +/- 0.9 vs. 4.1 +/- 1.0 mumol/g; P <
      .05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7635423
TI  - Improved hepatocyte in vitro maintenance in a culture model with woven
      multicompartment capillary systems: electron microscopy studies.
AB  - Primary pig hepatocytes form a tissuelike structure in an in vitro culture model
      that has provision for three-dimensional cell orientation, cell aggregation,
      decentralized cell perfusion with low metabolite gradients, integral oxygenation,
      and nonparenchymal cell coculture. Scanning electron microscopy (SEM) has shown
      that hepatocytes spontaneously form aggregates in a three-dimensional structure
      between and on the surface of artificial capillaries. Transmission electron
      microscopy (TEM) has shown that after 7 weeks of in vitro perfusion, the cell
      ultrastructure remains similar to that of the parenchyma in vivo. Golgi
      complexes, active membrane processes, reorganization of cell junctions, and bile
      canaliculi-like intercellular spaces were demonstrated.

PMID- 7635424
TI  - Synaptosomal glutamate transport in thioacetamide-induced hepatic encephalopathy
      in the rat.
AB  - Dysfunction of excitatory glutamatergic neurotransmission has been implicated in
      the cause of hepatic encephalopathy. Brain microdialysis studies in various
      animal models of portal systemic encephalopathy (PSE) and encephalopathy
      associated with acute liver failure, have established that an increase in
      extracellular glutamate occurs but the mechanisms of this are unclear. We have
      measured oxygen consumption, citrate synthase activity (as indices of energy
      state and mitochondrial content, respectively), calcium-dependent glutamate
      release, and high-affinity, sodium-dependent glutamate uptake by synaptosomes
      prepared from rats with thioacetamide-induced encephalopathy. (2 doses of
      thioacetamide 200 mg/kg with a 24-hour interval). Synaptosomes were prepared
      either by a modified P2 method (glutamate release study) or by discontinuous
      sucrose density gradient centrifugation (all other studies). There was no
      significant difference in synaptosomal oxygen consumption, citrate synthase
      activity, glutamate release, total synaptosomal glutamate content, or the Kd for
      glutamate uptake between the encephalopathy group and the controls. However,
      there was a marked decrease in the maximal velocity of transport (Vmax) for
      glutamate uptake in synaptosomes from encephalopathic rats, 2.64 versus 4.40
      nmol/min/mg (P < .05). The results of this study provide evidence of impaired
      glutamate uptake in the rat thioacetamide model of hepatic encephalopathy, which
      could account for the elevated extracellular glutamate seen in the condition.

PMID- 7635425
TI  - Loss of angiotensin-II receptors in portal hypertensive rabbits.
AB  - Decreased splanchnic vascular response to exogenous angiotensin-II (A-II)
      infusion in portal hypertension has recently been documented. A-II receptor
      density and binding affinity in the mesenteric artery, portal vein, and adrenal
      gland of normal and portal hypertensive rabbits were studied. Portal hypertension
      was induced by partial portal vein ligation 3 weeks before study. There were no
      significant differences in serum concentrations of sodium, potassium, A-II, serum
      osmolality, or hematocrit between normal and portal hypertensive rabbits. The
      portal hypertensive portal vein exhibited a 60% fall in A-II receptor number from
      65.1 +/- 0.3 fmol/mg in normal to 27.0 +/- 8 fmol/mg (P < .05) in portal
      hypertension. A significant decrease in receptor number occurred in the portal
      hypertensive mesenteric artery, 224 +/- 39 fmol/mg compared with 345 +/- 45
      fmol/mg in normal rabbits, and in the adrenal cortex 6.8 +/- 1.3 pmol/mg compared
      with 12.1 +/- 2.5 pmol/mg in normal controls (P < .05). No significant difference
      in A-II receptor affinity was observed in tissues studied between normal and
      portal hypertensive rabbits. Autoradiographic study on A-II receptors was
      consistent with data from membrane binding assays. Receptor subtype analysis
      showed exclusive type I receptor binding in the mesenteric artery and portal
      vein. We conclude there is a global reduction in the A-II receptor number in
      portal hypertension that may mediate much of the decreased response to A-II seen
      in this disorder. This loss of the A-II receptor may partially explain
      hemodynamic derangements peculiar to portal hypertension.

PMID- 7635426
TI  - Ascorbic acid inhibits chemically induced uroporphyria in ascorbate-requiring
      rats.
AB  - Ascorbate was previously shown to suppress accumulation of uroporphyrin (URO) in
      cultured chick embryo hepatocytes and to competitively inhibit microsomal
      oxidation of uroporphyrinogen catalyzed by cytochrome P4501A2. Here we used the
      Osteogenic Disorder Shionogi (ODS) mutant rat, which cannot synthesize ascorbic
      acid, to examine the in vivo effect of ascorbic acid on hepatic URO accumulation
      caused by treatment with 3-methylcholanthrene (MC) and 5-aminolevulinate (ALA).
      Female mutant rats maintained on three levels of dietary ascorbate (15,200, and
      800 ppm) were treated for a total of 24 days. On the 11th and 16th days, rats
      were administered 3-methylcholanthrene, and 5-aminolevulinate was present
      continuously in the drinking water from day 14. Hepatic URO accumulated at the
      two lowest ascorbate levels, but not at 800 ppm ascorbate. The latter dose
      produced normal hepatic ascorbate levels. Plasma ascorbate levels were
      proportional to the hepatic values. Male rats also accumulated URO at the low
      dietary dose of ascorbic acid. The methylcholanthrene-induced increase in
      microsomal levels of CYP1A1 and CYP1A2, total cytochrome P450, and activities of
      uroporphyrinogen oxidation and ethoxyresorufin deethylase were not affected by
      the dietary level of ascorbate. Neither male nor female Fischer 344 rats
      accumulated URO when treated with the MC/ALA regime. Hepatic ascorbate
      concentrations in these rats were five-fold to seven-fold higher than they were
      in mutant rats that developed uroporphyria on 150 ppm dietary ascorbate. In ODS
      rats fed ascorbate at 90 but not 900 ppm in the diet, hexachlorobenzene caused
      hepatic URO accumulation, indicating that the effect of ascorbic acid is not
      unique to the regimen using methylcholanthrene.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7635427
TI  - Regulation of the alpha 2(I) collagen gene transcription in fat-storing cells
      derived from a cirrhotic liver.
AB  - Fat-storing cells (FSC) are the main producers of type I collagen in both normal
      and fibrotic livers. In order to elucidate the molecular mechanisms controlling
      collagen expression in FSC, we examined the transcription of the alpha 2(I)
      collagen gene (COL1A2) in two distinct FSC clones, CFSC-2G and CFSC-5H, derived
      from a single CCl4-induced cirrhotic liver. The phenotype of CFSC-2G resembles
      freshly isolated FSC, whereas that of CFSC-5H mimics activated myofibroblasts.
      Cell transfection experiments showed that the upstream sequence between
      nucleotides -378 and -183 is essential for COL1A2 transcription in both FSC
      clones. This is the same promoter region that is transcriptionally active and
      contains the binding site of a multimeric protein complex that mediates TGF-beta
      stimulation of COL1A2 expression in dermal fibroblasts. We therefore examined the
      relative levels of endogenous and transfected COL1A2 transcription and their
      response to TGF-beta treatment in the two FSC clones. The results showed that
      CFSC-5H expresses a significantly higher level of the COL1A2 mRNA than CFSC-2G.
      They also showed that TGF-beta treatment increases both endogenous and
      transfected COL1A2 transcription in CFSC-2G but not in CFSC-5H. Interestingly,
      nuclear proteins from both FSC clones bind to the TGF-beta-responsive element
      more strongly than those from dermal fibroblasts. Altogether, the data suggest
      that collagen production in CFSC-5H cells has been already activated by the
      autocrine stimulation of TGF-beta. In contrast, CFSC-2G cells are only partially
      activated but can be easily recruited to produce collagen when stimulated by
      exogenous TGF-beta.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7635428
TI  - Downregulation of male-specific cytochrome P450s 2C11 and 3A2 in bile duct
      ligated male rats: importance to reduced hepatic content of cytochrome P450 in
      cholestasis.
AB  - The effects of bile duct ligation (BDL) on the activity and content of individual
      hepatic mixed-function oxidases (MFOs) was examined. Five days after BDL, hepatic
      microsomal total cytochrome P450 (CYP) content and NADPH-cytochrome P450
      reductase (P450-reductase) activity were reduced to 56% and 57% of control,
      respectively. MFO activities attributable to the sexually undifferentiated CYPs
      1A, 2A1, 2C6, and 2E1 were decreased to 32% to 52% of control, but the activities
      of two male sex-specific CYPs, 2C11 and 3A2, were reduced to a significantly
      greater extent (P < .05). The microsomal contents of CYP proteins 2C6 and 2E1
      were decreased after BDL to 61% and 63% of control, whereas 2C11 and 3A2 proteins
      were 21% and 45% of control. Corresponding reductions of the messenger RNA (mRNA)
      species for CYP 2C11 (9% of control) and 3A2 (37%) were detected, whereas there
      was no reduction of 2C6 mRNA. These findings are consistent with downregulation
      of the CYP 2C11 and 3A2 genes. Nuclear run-on studies performed 3 days after BDL
      showed that there was a generalized impairment of gene transcription after BDL,
      but a disproportionate reduction in transcription of CYPs 2C11 and 3A2. A
      possible explanation for downregulation of CYP 2C11 and 3A2 was provided by the
      observation that serum estradiol concentrations were threefold greater in BDL
      male rats, while serum testosterone was reduced; estradiol is known to
      downregulate CYPs 2C11 and 3A2. It is concluded that male sex-specific CYP
      enzymes are decreased to a greater extent than other microsomal proteins in BDL
      male rats.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7635429
TI  - Intracellular pH regulation in Hep G2 cells: effects of epidermal growth factor,
      transforming growth factor-alpha, and insulinlike growth factor-II on Na+/H+
      exchange activity.
AB  - Intracellular pH (pHi) plays an important role in the metabolic activation of
      quiescent cells after a proliferative stimulus, and Na+/H+ exchange activity is
      required for growth in some extrahepatic tumors. To investigate intracellular
      acid/base homeostasis in hepatoma cells and the effects of putative liver growth
      factors on Na+/h+ exchange activity, we have studied intracellular pH (pHi)
      regulation in Hep G2 cells, a well-differentiated hepatoma cell line, both in
      resting conditions and after administration of epidermal growth factor (EGF),
      transforming growth factor-alpha (TGF alpha), and insulinlike growth factor-II
      (IGF-II). The effects of fetal calf serum, TGF alpha, and amiloride on 3H
      Thymidine incorporation were also studied. Amiloride (1 mmol/L) and external Na+
      removal decreased baseline pHi in both HEPES and KRB. In HEPES, cells recovered
      from an acid load (20 mmol/L NH4Cl) by an amiloride inhibitable Na+/H+ exchange.
      In KRB, an additional, DIDS-inhibitable, Na(+)- and HCO3- dependent, but Cl(-)
      independent acid extruder (Na:HCO3 cotransport) was activated. No evidence was
      found for a Cl/HCO3 exchange acting as acid loader. Administration of EGF and TGF
      alpha, but not of IGF-II, induced a dose-dependent, amiloride-inhibitable
      increase in baseline pHi, together with an increase in Na+/H+ exchange activity,
      shifting to the right the JH/pHi curve. Finally, 3H-thymidine incorporation in
      Hep G2 cells, in the presence of FCS or TGF alpha, was strongly inhibited by
      amiloride. In conclusion, in Hep G2 cells, pHi is mainly regulated by Na+/H+
      exchange, which activity can be stimulated by EGF and TGF alpha, but not by IGF
      II. Administration of TGF alpha stimulates DNA synthesis, an effect that is
      blocked by amiloride, an inhibitor of Na+/H+ exchanger. These data suggest that
      Na+/H+ exchange activation may play a critical role in the growth of some hepatic
      tumors.

PMID- 7635430
TI  - Reduced antioxidative capacity in liver mitochondria from bile duct ligated rats.
AB  - Lipid peroxidation and antioxidative mechanisms were investigated in liver
      mitochondria from bile duct ligated rats (BDL rats) and correlated with the
      activity of enzyme complexes of the electron transport chain. In comparison to
      pair-fed control rats, BDL rats had increased concentrations of thiobarbituric
      acid reacting substances (TBARS) per gram of liver and per milligram of
      mitochondrial protein 3, 7, 14, and 28 days after surgery. The hepatic
      glutathione (GSH) content was decreased in BDL rats 28 days after surgery when
      expressed per gram of liver but equal between BDL and control rats when expressed
      per liver. The mitochondrial GSH content was decreased in BDL rats by 20% to 33%
      from day 7 after surgery. The concentrations of ubiquinone-9 and ubiquinone-10,
      substances involved in electron transport and efficient antioxidants, were both
      decreased in BDL rats 14 and 28 days after surgery per gram of liver and per
      milligram of mitochondrial protein. When expressed per liver, ubiquinone-9 was
      decreased in BDL rats from day 7 after surgery. In comparison with controls, the
      decrease in total mitochondrial ubiquinone content in BDL rats averaged 52% 14
      days and 38% 28 days after surgery. The activity of the succinate:ferricytochrome
      c oxidoreductase (complexes II and III of the electron transport chain) was
      decreased in BDL rats at days 7, 14, and 28 after surgery, and the activity of
      the ferrocytochrome c:oxygen oxidoreductase (complex IV) was reduced at 14 and 28
      days after surgery. The mitochondrial concentration of TBARS showed a negative
      and the concentrations of GSH and ubiquinone a positive correlation with the
      activity of the succinate:ferricytochrome c oxidoreductase.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7635431
TI  - Differential activation of transcription factors NF-kappa B and AP-1 in rat liver
      macrophages.
AB  - Liver macrophages (Kupffer cells) respond to many stimulations with the
      production of bioactive substances including cytokines, eicosanoids, and
      inorganic radicals. In this study the activation of transcription factors by
      substances inducing cytokine gene expression or superoxide formation in rat
      Kupffer cells was examined. Using primary cultures of rat Kupffer cells the role
      of NF-kappa B and activator protein 1 (AP-1) in the expression of the tumor
      necrosis factor-alpha (TNF-alpha) gene by lipopolysaccharide (LPS) was
      investigated. Both transcription factors were strongly activated but with
      different kinetics. Maximal DNA-binding activity was induced with 50 ng of LPS/mL
      of medium and persisted for at least 24 hours. At that time, NF-kappa B- as well
      as AP-1-DNA complexes decreased their mobilities in native gels. Among the
      cytokines tested only TNF-alpha and macrophage colony-stimulating factor (M-CSF)
      were able to activate NF-kappa B in Kupffer cells. Phorbol ester and zymosan
      activated AP-1 but not NF-kappa B; the treatment of zymosan yielding a modified
      form of AP-1. Of all substances found to interfere with TNF-alpha production by
      Kupffer cells (pyrrolidine dithiocarbamate, dexamethasone, prostaglandin E2,
      interleukin [IL]-4, IL-10, and transforming growth factor-beta [TGF-beta]) only
      pyrrolidine dithiocarbamate was able to completely inhibit the activation of NF
      kappa B by LPS. Although not abrogating the LPS activation of NF-kappa B,
      dexamethasone inhibited that of AP-1. The results indicate a direct participation
      of NF-kappa B in the regulation of TNF-alpha synthesis and a differential effect
      of LPS on NF-kappa B and AP-1, respectively.

PMID- 7635432
TI  - Rat hepatocytes attach to laminin present in liver biomatrix proteins by an
      Mg(++)-dependent mechanism.
AB  - Laminin belongs to a family of proteins that contains at least seven variants.
      Together with fibronectin, it is the most important cell-adhesion protein. Recent
      data from various laboratories have suggested that liver sinusoidal laminins
      differ from Engelbert-Holmes-Swarm tumor laminin (laminin 1), because the former
      contain alpha 2 instead of alpha 1 chains. Therefore, we compared the adhesion of
      hepatocytes to laminin 1 and a matrix extracted with dilute acetic acid from
      liver biomatrix (LBP). We show that LBP contains laminin and that this
      extracellular matrix protein is the main adhesion protein. Close to 70% of the
      hepatocytes attach to LBP after 15 minutes of incubation at 37 degrees C. Cell
      adhesion was Mg++ and Mn(++)-dependent and Ca(++)- and insulin-independent.
      Ethylenediaminetetraacetic acid prevented cell adhesion in the presence of
      divalent cations. We show that synthetic cell-adhesion peptide sequences present
      in laminin 1 (RGD and YIGSR) or an antibody to the cell-binding domain (SIKVAV)
      of the alpha 1 chain do not prevent hepatocyte adhesion to LBP. We also show that
      the LBP has cell specificity; hepatocytes adhere to it preferentially when
      compared with other epithelial and mesenchymal cell lines. We suggest that
      because of the differences in chain composition of laminin 1 and liver sinusoidal
      laminins as well as the described differences in cell adhesion to the two
      substrata, further studies are needed to determine the actual composition of
      liver laminin and establish the chains and domains to which hepatocytes adhere.

PMID- 7635433
TI  - Activation of Na+/H+ exchanger by hepatocyte growth factor in hepatocytes.
AB  - The effect of the hepatocyte growth factor (HGF) on the Na+/H+ exchanger was
      studied using primary cultured hepatocytes. HGF induced intracellular pH (pHi)
      elevation of 0.10 pH units in hepatocytes cultured for 4 to 7 hours; the response
      was lower after other culture periods. Even with the same culture period,
      intercellular heterogeneity was found in the responsiveness to HGF. This
      heterogeneity may be partially accounted for by the weak but significant
      correlation observed between the basal pHi level and the degree of pHi elevation
      caused by HGF in hepatocytes. The pHi elevation caused by HGF was blocked on
      pretreatment of the hepatocytes with amiloride, suggesting that HGF activates the
      Na+/H+ exchanger. This hypothesis was confirmed by the fact that HGF increased
      the initial rapid rate of cell alkalization of acid-loaded hepatocytes. The
      tyrosine kinase inhibitor, genistein, also blocked the elevation, consistent with
      the fact that HGF receptor/c-met has a tyrosine kinase domain. To clarify the
      signal transduction pathway from tyrosine kinase to the Na+/H+ exchanger, we
      examined the effects of inhibitors of other kinases (H-7, H-8, and W-7) on the
      HGF-induced pHi elevation and found that only W-7 blocked it. This pHi elevation
      was also prevented on preincubation of the hepatocytes with thapsigargin, which
      blocks the calcium response caused by HGF. These results suggest that HGF
      activates the Na+/H+ exchanger in hepatocytes through a tyrosine kinase
      calcium/calmodulin-dependent pathway.

PMID- 7635435
TI  - Terminology for hepatic allograft rejection. International Working Party.

PMID- 7635434
TI  - Transport characteristics of three fluorescent conjugated bile acid analogs in
      isolated rat hepatocytes and couplets.
AB  - The transport properties of three different synthetically prepared fluorescent
      conjugated bile acid analogs (FBA), all with the fluorophore on the side chain,
      were determined using isolated rat hepatocytes and hepatocyte couplets. The
      compounds studied were cholylglycylamidofluorescein (CGamF), cholyl(N epsilon
      nitrobenzoxadiazolyl [NBD])-lysine (C-NBD-L), and chenodeoxycholyl-(N epsilon
      NBD)-lysine (CDC-NBD-L). When hepatocytes were incubated at 37 degrees C with 0.3
      mumol/L of FBA and 0.15 mol/L of Na+, cell fluorescence increased linearly with
      time at a rate (U/min) of 7.8 +/- 0.5 for CGamF, 7.2 +/- 0.3 for C-NBD-L, and
      13.7 +/- 1.0 for CDC-NBD-L (mean, +/- SE; n = 40 to 90). Uptake was concentration
      dependent for concentrations less than 20 mumol/L and was saturable. The
      Michaelis constant (Km) value (mumol/L) for CGamF was 10.8, for C-NBD-L was 3.8,
      and for CDC-NBD-L was 3.0. In the absence of Na+, the uptake rate was decreased
      by 50% for CGamF and by 38% for C-NBD-L; but uptake of CDC-NBD-L was unchanged
      and thus Na+ independent. Cellular uptake of all three derivatives was specific
      to hepatocytes and was absent in several nonhepatocyte cell lines. For CGamF and
      C-NBD-L, both Na(+)-dependent and Na(+)-independent uptake was inhibited by 200
      fold excess concentrations of cholyltaurine, dehydrocholyltaurine, and cholate,
      but for CDC-NBD-L, these nonfluorescent bile acids did not inhibit initial
      uptake. The intracellular fluorescence of CGamF was strongly pH dependent at an
      excitation wavelength of 495 nm, but pH independent at 440 nm excitation. In
      contrast, intracellular fluorescence of C-NBD-L and CDC-NBD-L was pH independent.
      All three FBA were secreted into the canalicular space of approximately 50% to
      60% of couplets. Cellular adenosine triphosphate (ATP) depletion with either CN-
      or atractyloside inhibited secretion of all three FBA. The multispecific organic
      anion transporter (MOAT) inhibitor, chlorodinitrobenzene, blocked secretion of
      fluorescent MOAT substrates at a concentration of 1 mumol/L. At this
      concentration it did not affect secretion of the three FBA. At higher
      concentrations, chlorodinitrobenzene partially inhibited the canalicular
      secretion of CGamF but not the other two FBA. In conclusion, all three FBA are
      secreted by canalicular membrane bile acid transporters, but the sinusoidal
      uptake characteristics of CGamF and C-NBD-L are more similar than those of CDC
      NBD-L to the transport properties of cholyltaurine. Therefore, C-NBD-L appears to
      be the best of the three for studies of conjugated trihydroxy-bile acid transport
      in hepatocytes.

PMID- 7635436
TI  - A young man with a solitary hepatic mass.

PMID- 7635437
TI  - Ligation: endoscopic treatment of choice for patients with bleeding esophageal
      varices?

PMID- 7635438
TI  - Wherefore art thou liver disease associated with alpha-1 antitrypsin deficiency?

PMID- 7635439
TI  - Transport proteins and molecular biology: is cloning the beginning or the end?

PMID- 7635440
TI  - Hepatitis C: IIb (IV) or not IIb (IV) that is the question.

PMID- 7635441
TI  - Uridine diphosphate glucoronosyl transferases, candidate antigens of liver-kidney
      microsomal antibodies in hepatitis delta virus-infected patients.

PMID- 7635442
TI  - Creatine kinase-BB: markedly increased in fulminant hepatic failure caused by
      massively disseminated lymphoma cells in the liver.

PMID- 7635443
TI  - Reporting by digital speech recognition.

PMID- 7635445
TI  - Differential expression of the pS2 protein in the human prostate and prostate
      cancer: association with premalignant changes and neuroendocrine differentiation.
AB  - The distribution of the estrogen inducible pS2 protein was investigated in benign
      and malignant prostate tissue by the avidin-biotin complex method. Prostate
      tissue obtained from 20 patients without clinical and histological evidence of
      malignant disease consistently lacked pS2 immunoreactivity. Conversely,
      nonneoplastic tissue from 36 total prostatectomies with locally advanced prostate
      cancer showed a variable degree of pS2 reactivity in normal or hyperplastic
      glands and in prostatic intraepithelial neoplasia (PIN) adjacent to the cancerous
      lesions. This suggests that the pS2 gene expression detected in nonmalignant
      tissue may be related to early premalignant changes of prostate glands harboring
      significant carcinomas. In prostate cancer the pS2 protein was detected in close
      association with neuroendocrine (NE) differentiation as assessed by Chromogranin
      A (Chr A) immunoreactivity. Double labeling techniques showed that pS2
      immunoreactivity recognizes both endocrine (Chr A-positive) and adjacent exocrine
      (Chr A-negative) cell types within NE foci. Whereas pS2 expression was
      consistently confined to NE differentiation in untreated tumors, carcinomas that
      relapsed after hormonal therapy showed increased pS2 immunoreactivity, even in
      the absence of NE features. The differential expression of the pS2 peptide in
      nonneoplastic tissue from patients with and without malignant disease indicates
      that pS2 immunohistochemistry may be useful in the diagnostic evaluation of
      negative biopsy specimens. Furthermore, the results suggest that the
      immunohistochemical spectrum of pS2 in prostate cancer may include endocrine
      differentiated and presumably related cell populations.

PMID- 7635444
TI  - Glial cytokines in Alzheimer's disease: review and pathogenic implications.
AB  - The roles of activated glia and of glial cytokines in the pathogenesis of
      Alzheimer's disease are reviewed. Interleukin-1 (IL-1), a microglia-derived acute
      phase cytokine, activates astrocytes and induces expression of the astrocyte
      derived cytokine, S100 beta, which stimulates neurite growth (and thus has been
      implicated in neuritic plaque formation) and increases intracellular free calcium
      levels. Interleukin-1 also upregulates expression and processing of beta-amyloid
      precursor proteins (beta-APPs) (thus favoring beta-amyloid deposition) and
      induces expression of alpha 1-antichymotrypsin, thromboplastin, the complement
      protein C3, and apolipoprotein E, all of which are present in neuritic plaques.
      These cytokines, and the molecular and cellular events that they engender, form a
      complex of interactions that may be capable of self-propagation, leading to
      chronic overexpression of glial cytokines with neurodegenerative consequences.
      Self-propagation may be facilitated by means of several reinforcing feedback
      loops. beta-Amyloid, for instance, directly activates microglia, thus inducing
      further IL-1 production, and activates the complement system, which also leads to
      microglial activation with IL-1 expression. Self-propagation also could result
      when S100 beta-induced increases in intraneuronal free calcium levels lead to
      neuronal injury and death with consequent microglial activation. Such chronic,
      self-propagating, cytokine-mediated molecular and cellular reactions would
      explain the progressive neurodegeneration and dementia of Alzheimer's disease.

PMID- 7635446
TI  - Cervical carcinoma with glandular differentiation: histological evaluation
      predicts disease recurrence in clinical stage I or II patients.
AB  - Pathologists confront questions concerning the clinical implications of the more
      complex, evolving histopathologic classification in cervical carcinoma with
      glandular differentiation (CCGD) and the associated precursor intraepithelial
      lesions. Pseudoneoplastic pitfalls, such as microglandular hyperplasia,
      constitute the subject of recent reports, but the extent of misinterpretation for
      CCGD is unknown. To address these issues, we retrospectively reviewed all the
      histopathologic material for 67 patients treated for early clinical stage (I or
      II) CCGD. Two patients (3%) had pseudoneoplastic glandular lesions (two
      microglandular hyperplasias). The remaining 65 CCGDs included 35 pure
      adenocarcinomas (18 mucinous, six serous, five endometrioid, five clear cell, and
      one adenoid cystic), 26 adenosquamous carcinomas (17 showed > or = 50% and nine
      showed > 10% but < 50% squamous differentiation-all nonkeratinizing; four were
      predominantly glassy cell type, and the others showed the following
      adenocarcinoma component differentiation: 11 mucinous, eight serous, and three
      endometrioid) and four villoglandular papillary adenocarcinomas (all four were
      mucinous). In situ carcinoma was identified in 54%. The two patients with
      pseudoneoplastic lesions were disease free (after 96 and 108 months). Twenty-one
      patients with CCGD had recurrent disease at 4 to 144 months (mean, 45; median,
      18) including three local recurrences, 10 with distant metastasis, and eight with
      both. Thirty-five patients with CCGD were disease free at 12 to 216 months follow
      up (mean, 80.6; median, 65). Adenosquamous (P < .0002, predictive value [PV] =
      .68) and serous differentiation (P < .05, PV = .61) were the only histological
      types associated with disease recurrence. Vascular space invasion (P < .0002, PV
      = .7), deeper invasion (P < .0005), nuclear grade (P = .002, PV = .51), larger
      tumors on clinical exam (P < .01) or pathological evaluation (P < .01), and
      presence of pelvic lymph node metastasis at surgery (P < .05, PV = .7) are
      additional features associated with recurrent disease. A combination of
      adenosquamous or serous differentiation and vascular space invasion maximized PV
      for recurrent disease at a level of .75. Mucinous, endometrioid, or clear cell
      histological types, architectural grade, or the distinction between clinical
      stages I and II were not associated with recurrent disease. None of the four
      patients with villoglandular papillary adenocarcinoma exhibited recurrent
      disease, but confirmation of this histological subtype's prognostic value was
      hindered by the small number of cases identified (P = .16). Adenosquamous and
      serous differentiation, nuclear grading, pathological evaluation of vascular
      space and lymph node involvement, and recognition of pseudoneoplastic glandular
      lesions helped predict recurrent disease in low clinical stage CCGD in this
      retrospective study.

PMID- 7635447
TI  - Pathology of tumor-stroma interaction in melanoma metastatic to the skin.
AB  - Tumor invasion and metastasis formation largely depend on tumor-stroma
      interaction. In the present study morphological correlates of tumor-stroma
      interaction were examined in 344 melanoma lesions metastatic to the skin. In
      particular, the presence of simple infiltration into the surrounding dermis or
      subcutis without evident stromal reaction, the incorporation of pre-existent
      dermal collagen or subcutaneous fat cells into the tumor bulk, and the formation
      of a peritumoral capsule or intratumoral fibrous septa were evaluated. Our
      results showed that simple infiltration into the surrounding tissue as well as
      the incorporation of pre-existent stroma tissue without destruction is associated
      with poor outcome, whereas capsule and fibrous septa are favorable prognostic
      signs, particularly in subcutaneous lesions. Remarkably, simple infiltration is a
      prognostic indicator independent of the location of the metastasis (locoregional
      or distant), as shown by multivariate analysis. These data indicate that
      morphological aspects of tumor-stroma interaction in metastatic skin lesions of
      melanoma may reflect biological behavior of the tumor cells, may facilitate a
      pathological subclassification of metastatic melanoma in addition to clinical
      data, and are directly related to the patient's outcome.

PMID- 7635448
TI  - Role of cytokines in distribution and differentiation of dendritic
      cell/Langerhans' cell lineage in human primary carcinomas of the lung.
AB  - The possibility that production of some cytokines in the carcinoma
      microenvironment is associated with the presence and differentiation of cells
      belonging to the dendritic cell (DC)/Langerhans' cell (LC) lineage was
      investigated. Immunohistochemical examination showed the presence of
      intraepithelial LCs (CD1a- and S100-positive cells) in 6 of 10 squamous cell
      carcinomas and in 8 of 10 adenocarcinomas. Langerhans' cells were mainly located
      close to lymphoid aggregates. In situ hybridization performed in four cases
      (three LC positive and one LC negative) of squamous cell carcinoma and in five
      cases (four LC positive and one LC negative) of adenocarcinoma showed that some
      mononuclear cells in the interstitium displayed hybridization with granulocyte
      macrophage-colony stimulating factor (GM-CSF), tumor necrosis factor-alpha (TNF
      alpha), and interleukin 1-beta (IL1 beta) cDNA probes. Only in LC-positive
      carcinomas did epithelial cells close to lymphoid aggregates display small
      amounts of GM-CSF and TNF alpha mRNA expression. Immunohistochemical analysis
      performed in the 20 cases of lung carcinoma showed that epithelial cells in
      tumors with lymphoid aggregates and LCs were immunoreactive with antihuman GM-CSF
      monoclonal antibody. Specimens negative for GM-CSF contained very few LCs.
      Northern blot analysis was used to investigate GM-CSF, TNF alpha, IL1 alpha, and
      IL1 beta mRNA expression in six human lung carcinoma cell lines. A constitutive
      expression of TNF alpha mRNA was found in all of them, whereas only three showed
      a low constitutive expression of GM-CSF mRNA. In the latter three cell lines
      treatment with phytohemagglutinin (PHA)-stimulated peripheral blood lymphocyte
      (PBL) supernatant (PHA-SUP) upregulated GM-CSF mRNA expression and induced that
      of IL1 alpha mRNA. Carcinomatous epithelial cells producing small amounts of
      cytokines could promote the recruitment of cells of DC/LC lineage. Subcellular
      factors produced by reactive lymphocytes and/or macrophages may influence the
      production of GM-CSF and IL1 alpha by various epithelia. Up-regulation of this
      production could favor the arrival and differentiation of DCs and activate LC
      functions.

PMID- 7635449
TI  - Histological grading of breast carcinomas: a study of interobserver agreement.
AB  - Interobserver variation in the histological grading of breast carcinoma was
      investigated using the hypothesis that optimal fixation, more precise grading
      guidelines, some experience, the use of training and test sets, and a comparison
      of results with an expert group might allow higher levels of agreement. For the
      training sets sections from 50 consecutive cases of breast carcinoma received at
      the Sir Charles Gairdner Hospital (SCGH) and fixed in both B5 and buffered formal
      saline (BFS) were graded by consensus of three pathologists at the SCGH and
      independently by consensus of two pathologists at the Nottingham City Hospital
      (NCH) using a modified Scarff-Bloom-Richardson histological grading system with
      guidelines as suggested by NCH pathologists. The section quality and degree of
      preservation of nuclear morphology were judged by NCH pathologists to be superior
      for B5-fixed material. Complete agreement in grade between SCGH and NCH results
      was achieved for 83.3% of B5-fixed cases and 73.5% of BFS-fixed cases (P = .05)
      with relative disagreement rates (RDRs) of 0.15 and 0.29 and kappa statistic
      values of 0.73 and 0.58, respectively. Approximately 80% complete agreement was
      achieved for tubule formation, nuclear score, and mitotic count, with RDRs
      ranging from 0.19 to 0.27 and kappa values from 0.46 to 0.69. There was a
      consistent bias in the SCGH results toward a higher tubule score in both B5- and
      BFS-fixed material because of a difference in interpretation of cribriform or
      complex gland patterns and a consistent bias in SCGH results toward a lower
      nuclear size/pleomorphism score for B5 and BFS material. For the test set
      sections from 50 further consecutive cases of breast cancer fixed in B5 were
      examined using similar criteria but taking into account the sources of error
      shown by the training set. Approximately 80% complete agreement was again
      achieved for grade components and grade (RDRs, 0.18 and 0.72). Systematic bias
      was reduced in the test set, but no other improvement was observed. Of the tumors
      designated as grade I by NCH, 87.5% were called grade I tumors by SCGH in the B5
      training set, 84.6% in the B5 test set, and 66.6% in the BFS training set. The
      levels of agreement shown in both the training and test sets were satisfactory
      and represented a significant improvement over our previous study, suggesting
      that experience and precise grading guidelines are of value. The similar levels
      of agreement in training and test sets suggest that reasonable results can be
      achieved without direct training by expert groups.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 7635450
TI  - Pulmonary vein stenosis.
AB  - Pulmonary vein stenosis (PVS) is a rare disorder. Accurate diagnosis often
      requires anatomical examination. We report four children with pulmonary vein
      stenosis. Autopsy showed bilateral lesions in two patients who were thought
      clinically to have unilateral disease. A diagnosis of PVS was made at autopsy in
      the third case. Intimal and medial fibromuscular proliferation was noted in
      extrapulmonary and intrapulmonary veins. Some of the fibromuscular proliferation
      were eccentric, resembling organized thrombi. In one case a focal organizing
      thrombus was found in a clinically unobstructed but anatomically narrowed veno
      atrial junction. In another case injection of contrast medium into the stenotic
      pulmonary vein (PV) showed anastomosis between PV and bronchial vessels as well
      as small pulmonary arteries. Bilateral hypertensive arteriopathy was observed in
      unilateral and bilateral PVS. Our histological finding of intrapulmonary venous
      lesions in the lobes in which PVS was not detected clinically suggests that
      during surgical correction of unilateral PVS multiple biopsies of the opposite
      lung may help to evaluate possible bilateral disease. Our study also suggests
      that thrombosis in a stenotic pulmonary vein may further compromise the lumen and
      contribute to the progression of pulmonary vein obstruction. The possible
      pathogenesis of bilateral pulmonary hypertensive arteriopathy in unilateral PVS
      also is discussed.

PMID- 7635451
TI  - Prognostic value of epidermal growth factor receptor expression in endometrioid
      endometrial carcinoma.
AB  - We report here a retrospective study of epidermal growth factor receptor (EGFR)
      expression in 140 patients with human endometrioid endometrial carcinoma (median
      period of follow-up, 43.8 months; ranging from 1 to 155 months). Tumor specimens
      were immunohistochemically examined for the overexpression of EGFR, and the
      correlation among EGFR status, various clinicopathologic parameters, and
      prognosis was statistically evaluated. Monoclonal antibody (clone 31 G 7), which
      recognizes the extracellular domain of the EGFR molecule, was used for
      immunostaining. Ninety-four of 140 cases were immunohistochemically positive for
      EGFR (67.1%). The presence or absence of EGFR did not correlate with surgical
      stage, depth of myometrial invasion (DI), or lymph node involvement, but did
      correlate with histological grade and patient's age. Furthermore, patients with
      EGFR-positive endometrial carcinoma had a statistically significant shorter
      length of survival than those with EGFR-negative tumors (P = .018). This trend is
      more apparent among the patients more than 50 years old (P = .003). When adjusted
      for surgical stage, DI, and patient age, EGFR status retained prognostic value by
      multivariate analysis. However, when adjusted for surgical stage, histological
      grade, DI, and patient age, EGFR status failed to retain prognostic value by
      multivariate analysis. The results of this study suggest that EGFR expression is
      correlated with histological grade and greater invasiveness of human endometrioid
      endometrial carcinoma.

PMID- 7635452
TI  - Adenomatous hyperplasia in cirrhotic livers: histological evaluation, cellular
      density, and proliferative activity of 35 macronodular lesions in the cirrhotic
      explants of 10 adult French patients.
AB  - We examined 41 consecutive cirrhotic liver explants from French patients for the
      presence of nodules of adenomatous hyperplasia (AH) and then analyzed these
      lesions, together with underlying cirrhosis (C) and associated hepatocellular
      carcinoma (HCC), for various histological parameters, cellular density, and
      proliferative activity. Thirty-five AHs were identified in 10 livers (prevalence,
      24%); seven of 10 were HCV positive. Hepatocellular carcinoma was more frequent
      in patients with AH than in patients without. The AHs consisted of 17 ordinary
      (OAH) and 18 atypical (AAH) adenomatous hyperplasia lesions. There was a
      malignant focus in five of the 18 AAHs. Wide areas of large liver cell dysplasia
      were frequent in OAH but never found in AAH. Obvious steatosis was frequent in
      HCC but exceptional in AAH and absent in OAH. There was a significant increase in
      cellular density in AAH and HCC as compared with C and OAH. Proliferative cell
      nuclear antigen immunostaining similarly showed an increase in proliferation from
      OAH or C to AAH and HCC. These data suggest that, in Europe as in Japan, one
      pathway of hepatocarcinogenesis is a multistep process in which AAH should be
      considered as a premalignant lesion very close to grade I HCC, while OAH seems to
      correspond to a regenerative nodule with limited proliferative ability.

PMID- 7635453
TI  - The proliferative activity in oral epithelial dysplasia analyzed by proliferating
      cell nuclear antigen immunostaining and argyrophilic nucleolar organizer region
      staining.
AB  - The proliferative activity of leukoplakia without dysplastic change (LP),
      epithelial dysplasia (ED), and squamous cell carcinoma (SCC) in the oral mucosa
      was examined by means of proliferating cell nuclear antigen (PCNA)
      immunostaining, silver-binding argyrophilic nucleolar organizer region (AgNOR)
      staining, and the frequency of mitotic figures. Significant differences in the
      labeling index of PCNA immunostaining (PI) and mitotic index (MI) were noted
      between LP and ED and between ED and SCC. The mean numbers of AgNORs (AI)
      significantly differed between ED and SCC. There was a significant positive
      correlation between PI and MI in samples of ED. However, there was no significant
      correlation between AI and other indexes. The number and the distribution of PCNA
      positive cells in ED varied among samples. Five samples with higher PI and MI
      indexes than the mean values were selected from those of dysplasia based on the
      correlation between PI and MI. Their histological features symptomatic of oral ED
      as defined by the World Health Organization (WHO) Collaborating Centre in 1978,
      were investigated and compared with 10 samples with lower indexes. Histological
      findings, such as "loss of polarity of the basal cells," "an increased nuclear
      cytoplasmic ratio," "cellular pleomorphism," and "enlarged nucleoli," were
      significant histological features of these five samples. This study showed that
      the four histological components described previously and the increased number of
      mitotic figures used as the index of proliferating activity were the main
      histological components related to severe ED of oral mucosa. They will provide a
      useful means of deciding the histopathological grade of oral ED.

PMID- 7635454
TI  - Human herpesvirus type 6 and cytomegalovirus in AIDS-associated Kaposi's sarcoma:
      no evidence for an etiological association.
AB  - Epidemiological studies indicate that acquired immune deficiency syndrome (AIDS)
      associated Kaposi's sarcoma (KS) may be caused by an infectious, preferentially
      sexually transmitted agent. Herpesviruses infections are common sexually
      transmitted diseases in homosexual men, who are also the main risk group for
      developing Kaposi's sarcoma. To evaluate a possible role of human herpesvirus-6
      (HHV-6) and cytomegalovirus (CMV) in the development of AIDS-associated KS, we
      investigated cutaneous AIDS-associated KS in 26 AIDS patients using the
      polymerase chain reaction (PCR) and immunohistochemistry (IHC) to detect the
      presence of HHV-6 and CMV. Human herpesvirus-6 was detected in nine of 26
      Kaposi's sarcoma specimens (all cases were HHV-6 subtype B) and in eight of 27
      normal skin specimens from human immunodeficiency virus (HIV) seropositive and
      HIV seronegative patients (one case was HHV-6 subtype A and seven cases were HHV
      6 subtype B). In two of four patients showing HHV-6 in KS of the skin, the virus
      also was detected in other investigated tissues, such as heart, lung, liver,
      kidney, and adrenals. Cytomegalovirus was detected only in AIDS-associated KS
      (seven of 26 KS specimens) and not in normal skin tissues of HIV-seropositive and
      HIV-seronegative patients. Cytomegalovirus was detected in other organs of those
      patients showing CMV in Kaposi's sarcoma. Our data indicate that the presence of
      HHV-6 and CMV in AIDS-associated KS most likely reflects disseminated viral
      infection. Human herpesvirus-6 and CMV may be cofactors but not the only
      causative agents for the development of AIDS-associated KS.

PMID- 7635455
TI  - Ehrlichiosis mimicking thrombotic thrombocytopenic purpura. Case report and
      pathological correlation.
AB  - Human ehrlichiosis is a tick-borne zoonosis caused by the newly described human
      hematotropic rickettsiae, Ehrlichia chaffeensis. The pathology and pathogenesis
      of human ehrlichiosis have not been adequately studied. Even with
      immunoperoxidase, the only previously known method to detect these organisms in
      tissue, ehrlichae are difficult or impossible to identify. This led many
      investigators to speculate that the pathogenesis of ehrlichiosis was not caused
      directly by the organism but could be caused by host-mediated injury. In this
      case study, a patient presented with rapidly progressive central nervous system
      symptoms and severe thrombocytopenia, prompting a presumptive diagnosis of
      thrombotic thrombocytopenic purpura (TTP). Despite corticosteroids, and later,
      antibiotics, the patient rapidly deteriorated and died. Postmortem examination
      showed hemorrhages in multiple organs and mononuclear inclusions of infection
      with a monocytic ehrlichia. Other findings included widespread lymphohistiocytic
      perivascular infiltrates, focal hepatic necroses, interstitial pneumonitis,
      interstitial nephritis, mononuclear phagocyte invasion and proliferation in
      splenic, liver, and bone marrow, and hemophagocytosis. The diagnosis was proven
      by serology, immunohistology with both polyclonal and monoclonal anti E
      chaffeensis, and polymerase chain reaction on paraffin-embedded tissues using E
      chaffeensis-specific oligonucleotide primers. The presence of numerous ehrlichia
      with notable tissue and cellular injury but without a marked host response
      indicate that unlike other cases of documented human ehrlichiosis, this patient
      died after significant direct ehrlichia-mediated injury, and that immune
      mechanisms initiated after ehrlichiosis played little if any role in the
      pathogenesis.

PMID- 7635456
TI  - Intrasellar neuronal choristoma associated with growth hormone-producing
      pituitary adenoma containing amyloid deposits.
AB  - The histological, immunocytochemical, and ultrastructural features of an
      intrasellar neuronal choristoma associated with pituitary growth hormone (GH)
      producing adenoma are reported. Immunohistochemistry studies and electron
      microscopy examination showed the adenoma cells to be positive for GH but
      negative for prolactin, and the neurons of the choristoma to have GH-releasing
      factor (GRF) neurosecretory activity. The adenoma also had many amyloid deposits
      in its extracellular space immunoreactive to GRF. This is the first report of the
      tumor containing amyloid deposits.

PMID- 7635457
TI  - Solid cell nests of the thyroid.

PMID- 7635458
TI  - Branchial cysts in thyroid and parathyroid glands.

PMID- 7635459
TI  - Positional mapping of loci in the DiGeorge critical region at chromosome 22q11
      using a new marker (D22S183).
AB  - The majority of patients with DiGeorge syndrome (DGS) and velo-cardio-facial
      syndrome (VCFS) and a minority of patients with non-syndromic conotruncal heart
      defects are hemizygous for a region of chromosome 22q11. The chromosomal region
      that is commonly deleted is larger than 2 Mb. It has not been possible to narrow
      the smallest region of overlap (SRO) of the deletions to less than ca 500 kb,
      which suggests that DGS/VCFS might be a contiguous gene syndrome. The saturation
      cloning of the SRO is being carried out, and one gene (TUPLE1) has been
      identified. By using a cosmid probe (M51) and fluorescence in situ hybridization,
      we show here that the anonymous DNA marker locus D22S183 is within the SRO,
      between TUPLE1 and D22S75 (probe N25). A second locus with weak homology to
      D22S183, recognized by cosmid M56, lies immediately outside the common SRO of the
      DGS and VCFS deletions, but inside the SRO of the DGS deletions. D22S183
      sequences are strongly conserved in primates and weaker hybridizing signals are
      found in DNA of other mammalian species; no transcripts are however detected in
      polyA+ RNA from various adult human organs. Probe M51 allows fast reliable
      screening for 22q11 deletions using fluorescence in situ hybridization. A
      deletion was found in 11 out of 12 DGS patients and in 3 out of 7 VCFS patients.
      Two patients inherited the deletion from a parent with mild (atypical) symptoms.

PMID- 7635460
TI  - The mutational demography of protein C deficiency.
AB  - The geographical distribution and prevalence of 256 single base-pair
      substitutions (105 of them being different) within the coding region of the human
      protein C (PROC) gene were correlated with their initial likelihoods of
      generation. A significant positive correlation was observed between these
      "mutational likelihoods" and the geographical dispersal of the PROC gene lesions
      within and between 16 different countries. This relationship could be attributed
      to the fact that, with few exceptions, high dispersal was only exhibited by CG-
      >TG and CG-->CA transitions, i.e. those substitutions that are known to arise de
      novo at the highest frequency. The statistical distribution of mutational
      likelihoods was as predicted on the basis of the PROC cDNA sequence alone,
      allowing however for the redundancy of the genetic code. These findings suggest
      (1) that genetic drift and lesion-specific selection have been of relatively
      minor importance in determining the mutational spectrum observed in the PROC gene
      and (2) that most multiple reports of particular substitutions in different
      geographical locations appear to reflect recurrent mutation rather than identity
      by-descent.

PMID- 7635461
TI  - An efficient screening procedure detecting six novel mutations in the LDL
      receptor gene in Swedish children with hypercholesterolemia.
AB  - Familial hypercholesterolemia (FH) is an autosomal semi-dominant disorder caused
      by defects in the low density lipoprotein receptor (LDLR) gene and is a well
      documented risk factor for developing cardiovascular disease. The LDLR genes of
      five Swedish children with FH were examined in this study. Initial mutation
      screening was performed by denaturing gradient gel electrophoresis (DGGE) with
      enzymatically amplified exon-sized fragments, each containing a tailing GC-rich
      requence. The GC-clamped fragments had been synthesized with a restriction site
      adjacent to the intron-corresponding sequence to allow detachment of the clamps,
      thereby rendering the fragments suitable for subsequent analysis by single-strand
      conformation polymorphism (SSCP) analysis of samples from patients with no DGGE
      detectable mutations. In addition, all the LDLR genes of the patients were
      screened for large alterations by restriction fragment length polymorphism
      analysis. Following this strategy, seven different, potentially disease-causing
      mutations were detected in the five children with FH. Six of the alterations,
      five single-base substitutions and one dinucleotide deletion, have not previously
      been described. DGGE detected six of the mutations and SSCP the seventh.

PMID- 7635462
TI  - Alcohol and aldehyde dehydrogenase genotypes and drinking behavior of Chinese
      living in Shanghai.
AB  - Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), the principal
      enzymes responsible for oxidative metabolism of ethanol, exist in multiple,
      genetically determined molecular forms. Widely different kinetic properties in
      some of these isozymes account for the individual differences in alcohol
      sensitivity. In this study we used the polymerase chain reaction/restriction
      fragment length polymorphism method to determine the genotypes of the ADH2 and
      ALDH2 loci of alcoholic and nonalcoholic Chinese living in Shanghai. We also
      investigated the subjects' drinking patterns by means of semistructured
      interviews. The alcoholics had significantly lower frequencies of the ADH2(2) and
      ALDH2(2) alleles than did the nonalcoholics, suggesting the inhibitory effects of
      these alleles for the development of alcoholism. In the nonalcoholic subjects,
      ADH2(2) had little, if any, effect, despite the significant effect of the
      ALDH2(2) allele in decreasing the alcohol consumption of the individual. Taken
      together, these results fit the proposed hypothesis for the development of
      alcoholism, i.e., drinking behavior is greatly influenced by the individual's
      genotypes of alcohol-metabolizing enzymes, and the risk of becoming alcoholic is
      proportionate with the ethanol consumption of the individual.

PMID- 7635463
TI  - Isolation and chromosomal localization of a human ATP-regulated potassium
      channel.
AB  - KATP channels are K+ channels whose activity is inhibited by the presence of and
      enhanced by the absence of cytosolic ATP. This property allows KATP channels to
      sense cellular intermediary metabolism and directly couple this information to
      the modulation of membrane excitability. Indeed, recent studies from our
      laboratory and others have suggested that activation of KATP channels during
      anoxia is important in the response and adaptation of central neurons to hypoxia.
      In order to identify KATP channels from human brain, we performed a polymerase
      chain reaction (PCR) using human cerebral cortex mRNA and primers derived from
      the ROMK1 sequence, a cDNA clone encoding an ATP-regulated potassium channel,
      recently isolated from rat kidney. We thus identified a novel 308-bp PCR product,
      pKCNJ1, whose expression was found to be restricted to a 3.0-kb band in the
      kidney by probing a human multiple tissue northern blot, pKCNJ1 was then used to
      isolate genomic clones and, using fluorescence in situ hybridization (FISH) to
      human metaphase chromosomes, was mapped to chromosome 11q.

PMID- 7635464
TI  - Heteroduplex analysis detects frameshift and point mutations in patients with
      acute intermittent porphyria.
AB  - We used heteroduplex analysis to screen for mutations in the porphobilinogen
      deaminase gene in 21 patients with acute intermittent porphyria (AIP). Unique
      banding patterns were investigated by direct sequencing of polymerase chain
      reaction products and, when indicated, sequencing of cloned DNA containing the
      exon of interest. Two frameshift mutations were found, a 2-bp deletion in exon 5
      and a 1-bp insertion in exon 7. Both mutations generate a premature stop codon.
      Two point mutations, in exons 10 and 14, were also observed. The C-->T mutation
      in exon 10 codes for an Arg173 to Trp substitution, while a G-->A mutation in
      exon 14 changes Trp283 into a premature stop codon. This study extends the
      spectrum of mutations that cause AIP and demonstrates the utility of heteroduplex
      analysis as a screening technique.

PMID- 7635465
TI  - X-chromosome methylation in manifesting and healthy carriers of
      dystrophinopathies: concordance of activation ratios among first degree female
      relatives and skewed inactivation as cause of the affected phenotypes.
AB  - The X-chromosome activity states of 11 manifesting carriers of
      dystrophinopathies, all with normal karyotypes, were estimated by restriction
      fragment length polymorphism (RFLP)-methylation analysis with the probes M27 beta
      (DXS255), p2-19(DXS605) and pSPT/PGK (PGK1) to test the role of skewed X
      inactivation ratios as the cause of their affected phenotypes. In eight cases
      preferential inactivation of the putative X chromosome carrying the normal
      dystrophin allele in > or = 90% of their peripheral lymphocytes was observed, two
      cases showed non-apparent deviant ratios (60:40 and 70:30) from the theoretically
      expected values around the mean of 50% and in one case the three markers employed
      yielded no information. The analysis of the X-inactivation ratio in six mother
      daughter pairs, all non-manifesting Duchenne muscular dystrophy (DMD) carriers,
      and in the close female relatives of the patients showed: (a) neither of the two
      X chromosomes was preferentially inactivated with respect to their parental
      origin; (b) a high concordance among the activation ratios of mothers and
      daughters, a result difficult to explain just in terms of random X-chromosome
      inactivation.

PMID- 7635466
TI  - Screening for naturally occurring apolipoprotein A-I variants: apo A-I(delta
      K107) is associated with low HDL-cholesterol levels in men but not in women.
AB  - Isoelectric focussing (IEF) in carrier ampholyte-generated pH gradients and
      hybrid isoelectric focussing (HIEF) in immobilized pH gradients under
      nondenaturing conditions were used in parallel to screen 5,500 plasma samples for
      naturally occurring variants of apolipoprotein A-I (apo A-I). The following
      defects were identified in four unrelated subjects heterozygous for apo A-I
      variants: apo A-I(delta K107)(2 x), apo A-I(K107M)(1 x), and apo A-I(E41R)(1 x).
      The later variant is a novel finding. Family studies did not reveal any
      association of apo A-I(K107M) and apo A-I(E41R) with dyslipidemia, but identified
      several heterozygotes for apo A-I(delta K107) who had low levels of high density
      lipoprotein (HDL)-cholesterol. Therefore, and since the apo A-I(delta K107) is
      the most frequent apo A-I variant in Germany (1: 5,000) we evaluated our data and
      that reported from 11 families with 32 heterozygous carriers and 30 unaffected
      controls. This analysis revealed that apo A-I(delta K107) is associated with
      lower HDL-cholesterol (-30%) and higher triglycerides (+48%) in men but not in
      women as compared with unaffected family members as well as with controls from
      the Prospective Cardiovascular Munster (PROCAM) study. Moreover, 11 of 15 male
      apo A-I(delta K107) heterozygotes but only 2 of 17 female apo A-I(delta K107)
      heterozygotes had HDL-cholesterol levels below the 20th percentile of sex-matched
      controls from the PROCAM study. We conclude that heterozygosity for apo A-I(delta
      K107) decreases HDL-cholesterol and increases triglycerides in men but not in
      women.

PMID- 7635467
TI  - Linkage studies in a kindred from Oklahoma, with familial benign (hypocalciuric)
      hypercalcaemia (FBH) and developmental elevations in serum parathyroid hormone
      levels, indicate a third locus for FBH.
AB  - A five-generation kindred (19 affected, two obligate carriers and 20 unaffected)
      from Oklahoma USA, in which familial benign (hypocalciuric) hypercalcaemia (FBH)
      was associated with a developmental elevation in serum parathyroid hormone (PTH)
      levels, has been investigated for linkage to the candidate chromosomal regions
      3q21-q24 and 19p13.3, 11q13, and 11p15, to which the genes for FBH, multiple
      endocrine neoplasia type 1 (MEN1) and PTH have been mapped respectively. By means
      of 17 polymorphic markers from these regions, linkage was excluded [LOD scores < 
      2.00 at (theta) = 0.05-0.25]. In addition, an analysis of multipoint crossovers
      and use of the LINKMAP program confirmed the exclusion from these regions. Thus,
      this form of FBH, designated the Oklahoma variant FBH(Ok), is not linked to
      markers that segregate with FBH, MEN1 and PTH; our results indicate further
      genetic heterogeneity and the presence of a third locus for FBH.

PMID- 7635468
TI  - Distribution of human endogenous retrovirus HERV-K genomes in humans and
      different primates.
AB  - The distribution of the human endogenous retrovirus (HERV)-K genome was
      investigated by Southern-blot analyses using a HERV-K-env DNA probe. With the
      exception of one DNA-sample, obtained from a Chinese individual in whom an
      amplification of HERV-K was detected, Southern-blot analyses yielded identical
      hybridization patterns with DNA from peripheral blood lymphocytes of 37 normal
      healthy blood donors, with DNA from six tumor cell lines, or with 23 DNA samples
      prepared from various carcinoma tissues. To elucidate whether the integration of
      HERV-K genomes into the primate lineage occurred as a single event or as an
      integration with later expansion, we further examined the evolutionary history of
      HERV-K by Southern blot analyses with DNA samples from different primate species.
      We detected HERV-K genomes in Macaca mulatta and Macaca silenus, which represent
      Old World monkeys, but not in prosimians (Galago demidovii) and New World
      monkeys, represented by Saguinus fuscicollis, Saguinus oedipus, and Callithrix
      iacchus. Thus, we assume that the infection of the primate lineage with HERV-K
      had occurred after the divergence of New World and Old World monkeys, but before
      the evolutionary expansion of large hominoids. In contrast to the apparent lack
      of HERV-K-env sequences in DNA from tissue of the New World monkey Saguinus
      oedipus (cotton-top marmoset), we found HERV-K-DNA in the B95-8 cell-line, which
      is a Saguinus oedipus leukocyte cell-line, immortalized in vitro by Epstein-Barr
      virus (EBV) and cultivated in human cells. It may be speculated that HERV-K-DNA
      or HERV-K-particles were introduced into these cells during in vitro
      transformation with EBV.

PMID- 7635469
TI  - Highly variable incidence of cystic fibrosis and different mutation distribution
      among different Jewish ethnic groups in Israel.
AB  - The incidence of cystic fibrosis (CF) and the frequency of disease-causing
      mutations varies among different ethnic and geographic populations. The Jewish
      population around the world is comprised of two major ethnic groups; Ashkenazi
      and non-Ashkenazi. The latter is further classified according to country of
      origin. In this study, we analyzed the incidence of CF and the distribution of CF
      mutations in the general Jewish population in Israel and in most of the Jewish
      ethnic subgroups. The disease frequency varies considerably among the latter.
      Among Ashkenazi Jews, the frequency of CF is 1:3300, which is similar to the
      frequency in most Caucasian populations. Among non-Ashkenazi Jews, the disease
      occurs at a similar frequency among Jews from Libya (1:2700), Georgia (1:2700),
      Greece and Bulgaria (1:2400), but is rare in Jews from Yemen (1:8800), Morocco
      (1:15000), Iraq (1:32000), and Iran (1:39000). So far, only 12 mutations have
      been identified in Israeli Jews, and this enables the identification of 91% of
      the CF chromosomes in the entire Jewish CF population. However, in each Jewish
      ethnic group, the disease is caused by a different repertoire of mutations. The
      frequency of identified mutations is high in Ashkenazi Jews (95%), and in Jews
      originating from Tunisia (100%), Libya (91%), Turkey (90%), and Georgia (88%).
      However, a lower frequency of mutations can be identified in Moroccan (85%),
      Egyptian (50%), and Yemenite (0%) Jews. For genetic counseling of a Jewish
      individual, it is necessary to calculate the residual risk according to ethnic
      origin. Carrier screening of healthy Jewish individuals is currently feasible for
      Ashkenazi Tunisian, Libyan, Turkish, and Georgian Jews. These results provide the
      required information for genetic counseling of Jewish CF families and screening
      programs of Jewish populations worldwide.

PMID- 7635470
TI  - Analysis of steroid 21-hydroxylase gene mutations in the Spanish population.
AB  - Steroid 21-hydroxylase deficiency is the major cause of congenital adrenal
      hyperplasia. Genotyping for deletions and nine point mutations in the CYP21 gene
      has been performed in 38 Spanish patients and their relatives by Southern blot
      analysis and allele-specific oligonucleotide hybridization. Three clinical
      variants were included in this study, viz., salt-wasting (SW, 21 patients),
      simple virilizer (SV, two patients), and late-onset (LO, 15 patients) forms.
      Twenty-three patient genotypes (16 SW, two SV, and five LO) were fully
      characterized. In both alleles, all but one of these severe forms (SW and SV)
      presented mutations that abolished or severely affected enzymatic activity.
      Patients with LO forms showed mutations that moderately impaired enzymatic
      activity in both alleles, or severe mutations in only one chromosome. Of 46
      chromosomes from severe forms, 41 were characterized in this study (89%). The
      most frequent mutation was an aberrant splicing site (655 A or C to G) in intron
      2, in 30% of these chromosomes. Deletions were found in 20%, and large gene
      conversions in 13% of these alleles. This screening allowed the characterization
      of 18 out of 30 LO chromosomes, the most frequent mutation being Val281Leu (37%).
      Severe mutations were found, in heterozygosis, in one third of LO patients.

PMID- 7635471
TI  - Amplifying dinucleotide microsatellite loci from bone and tooth samples of up to
      5000 years of age: more inconsistency than usefulness.
AB  - We have studied the feasibility of using dinucleotide-repeat microsatellites in
      the analysis of DNA from ancient bones and teeth. We have used three
      microsatellites (IVS8CA, IVS17BTA, and IVS17BCA) within the cystic fibrosis
      transmembrane conductance regulator gene in 28 DNA samples from bones and teeth
      of up to 5000 years of age. PCR amplification was successful in 71.4% of cases.
      The repeated analysis of each marker produced different genotypes in 97% of
      samples, and the same individual genotype was reproduced at least once in 45.5%
      of cases. Alleles differing from the originals consisted of additions or
      deletions of 1-39 dinucleotides. The mechanism by which alleles differing from
      the originals were amplified can be related to the marked degradation of the DNA,
      with repeat sequences of different length interacting with the partially degraded
      repeats of the amplified loci. The repeated analysis of each sample allowed us to
      produce data with some anthropological interest. Among the haptotypes detected in
      samples from Easter Island, two (16-32-13 and 23-32-13) were found in more than
      one sample. Similarly, three haplotypes (16-7-17, 16-7-13, and 16-24-13) were
      detected more than once in samples from the Basque Country. Although haplotypes
      in the Basque Country are amongst the commonest in European chromosomes, most of
      those detected in the Easter Island samples are not frequent in Europeans. Thus,
      the repeated typing of microsatellites allowed us to postulate the genotypes that
      might be present in the samples but dinucleotide markers do not seem to be
      reliable enough for genotyping ancient bone and teeth samples.

PMID- 7635472
TI  - A gene for blepharophimosis-ptosis-epicanthus inversus syndrome maps to
      chromosome 3q23.
AB  - Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is an autosomal
      dominant malformation of the eyelids that may severely impair visual function.
      Chromosomal aberrations involving chromosomes 3q23, 3p25 and 7p34 have been
      reported in BPES but the disease gene has not been hitherto localized by linkage
      analysis. We have mapped a gene for BPES to chromosome 3q23 in a large French
      pedigree (Zmax = 4.62 at Theta = 0 for probe AFM 182yc5 at locus D3S1549). The
      best estimate for the location of the disease gene is at locus D3S1549, between
      the loci D3S1292 and D3S1555 (maximum lod score of 5.10).

PMID- 7635473
TI  - An autosomal dominant retinitis pigmentosa family with close linkage to D7S480 on
      7q.
AB  - Retinitis pigmentosa is the most prevalent inherited disorder of the retina. It
      can be autosomal dominant (adRP), autosomal recessive (arRP) or X-linked (XLRP).
      A form of adRP mapping to chromosome 7q was reported in a large Spanish pedigree.
      We have typed DNA from the members of another Spanish family for polymorphic
      markers from the known candidate genes. Positive lod scores were obtained only
      for the markers located on 7q31-35, giving a maximum lod score of 2.98 (3.01 by
      multipoint analysis) at theta = 0.00 for D7S480. A brief clinical evaluation is
      given.

PMID- 7635474
TI  - Rh--plasma iron binding capacity association. New evidence.
AB  - The relationship between Rh phenotypes and the total iron binding capacity (TIBC)
      of plasma was studied in a sample from Medellin, Colombia. In a previous report
      from Santiago, Chile, children carrying the C Rh specificity had a higher level
      of TIBC than those having the specificity. The same association was found in
      young people from Medellin.

PMID- 7635475
TI  - Localisation of the human gene encoding the cytoskeletal protein talin to
      chromosome 9p.
AB  - The cytoskeletal protein talin is localised on the cytoplasmic face of the
      integrin family of adhesion receptors in cellular junctions with the
      extracellular matrix. Using polymerase chain reaction amplification and DNA from
      a panel of human-rodent somatic cell hybrids, we have assigned the talin gene to
      chromosome 9p. Deletions in 9p have been implicated in a variety of cancers,
      including malignant melanoma, and the concept that talin might be a candidate
      tumour suppressor gene is discussed.

PMID- 7635477
TI  - Somatic stability in chorionic villi samples and other Huntington fetal tissues.
AB  - We have studied different tissues from two affected fetuses with Huntington's
      disease (HD). In the first case the analysis was performed at 11 weeks of
      pregnancy; CAG repeats from seven different tissues were compared with the
      results obtained in the chorionic villi sample (CVS). We found 42 CAG repeats in
      all samples. In the second case the study was done at 12 weeks; eight tissues
      (including brain) were studied and compared with the CVS; in all of them, 44 CAG
      repeats were obtained. Our results show a somatic stability in the different
      analyzed tissues and suggest that mitotic instability can be a secondary
      consequence of neuronal degeneration and gliosis. Likewise, our data show great
      viability in the prenatal diagnosis (PD) of Huntington's disease using samples
      from any tissue.

PMID- 7635476
TI  - The 9-bp deletion in region V of mitochondrial DNA: evidence of mutation
      recurrence.
AB  - A deletion of one of the two copies of a 9-bp direct repeat sequence (CCCCCTCTA)
      in region V of mitochondrial DNA has previously been used as a polymorphic
      anthropological marker for people of east Asian origin, and to a lesser extent,
      in Oceanian and African populations. We report the presence of the 9-bp deletion
      in homoplasmy in skeletal muscle fibers and lymphocytes of a Spanish Caucasian
      individual. Other mitochondrial DNA polymorphisms associated with the 9-bp
      deletion characteristic of other populations were not present. Our results
      suggest that the 9-bp deletion probably originated independently in the maternal
      lineage of the propositus, and that it can thus be described as a recurrent
      mutation.

PMID- 7635478
TI  - An AT-deletion causing a frameshift in the arylsulfatase A gene of a late
      infantile metachromatic leukodystrophy patient.
AB  - A metachromatic leukodystrophy (MLD) patient affected with the late infantile
      form was found to be homozygous for an AT-deletion (2324delAT) in the
      arylsulfatase A gene. The mutation causes a frameshift at the beginning of exon 8
      leading to an early termination codon. The parents and unaffected brother of the
      patient were heterozygous for the microdeletion. The mutation was not detected in
      another 31 MLD Italian patients. No aberrant transcript caused by the mutation
      was revealed by the reverse transcription-polymerase chain reaction method.

PMID- 7635479
TI  - Dinucleotide repeat polymorphism in the proteolipoprotein (PLP) gene.
AB  - We report a dinucleotide polymorphism in the first intron of the proteolipid
      protein (PLP) gene with a heterozygosity frequency of 0.69 useful for molecular
      analysis of families with X-linked neurologic disorders characterized by
      dysmyelination of the central nervous system, Pelizaeus-Merzbacher Disease (PMD)
      and X-linked Spastic Paraplegia (SPG2).

PMID- 7635480
TI  - Three new dinucleotide repeat polymorphisms on human chromosome 9: D9S970,
      D9S971, and D9S972.
AB  - Three human chromosome 9-specific cosmid recombinants containing (CA)n
      microsatellites are described. Three microsatellite loci, D9S970, D9S971, and
      D9S972, were observed to have heterozygosities of 0.78, 0.84, and 0.82,
      respectively. Subchromosomal localizations were determined by R-banding and
      fluorescence in situ hybridization.

PMID- 7635481
TI  - Restriction polymorphisms of the ceruloplasmin gene on chromosome 3.
AB  - Using a probe isolated from a human liver cDNA library, polymorphisms were
      observed in the human ceruloplasmin gene with the enzymes PstI and MspI. The PstI
      polymorphism was frequent (allele frequencies, 0.46 and 0.54) whereas the
      polymorphisms found with MspI were rare.

PMID- 7635482
TI  - Two novel point mutations in the EGF precursor homology domain of the LDL
      receptor gene causing familial hypercholesterolemia.
AB  - Familial hypercholesterolemia is caused by mutations in the low density
      lipoprotein (LDL) receptor gene. Analysis of single-strand conformation
      polymorphisms of exons 10 and 11 of the LDL receptor gene from familial
      hypercholesterolemia heterozygotes indicated the presence of two mutations, which
      were characterized by DNA sequencing. One mutation (delta N466) was a 3-bp
      deletion in exon 10 that deletes Asn in codon 466. The other (intron 11 +1, G-
      >T) was a splice donor mutation at position +1 of intron 11.

PMID- 7635483
TI  - A novel polymorphism (6376 G/T) in intron 7 of the human protein C gene.
AB  - A novel polymorphism (6376 G/T) in intron 7 (17) of the human PROC gene has been
      identified by direct DNA sequencing. Restriction analysis with the use of
      mutagenic primers indicate that the allele frequencies are 0.17 (allele T) and
      0.83 (allele G), with a calculated heterozygosity of 28%.

PMID- 7635484
TI  - A human SHC-related sequence maps to chromosome 17, the SHC gene maps to
      chromosome 1.
AB  - The SHC gene encodes a protein that is thought to act as an adapter in many
      signal transduction pathways; the SHC protein probably facilitates the activation
      of RAS proteins in response to a variety of factors. We have mapped the human SHC
      gene and have identified a new SHC-related sequence. We have sequenced the region
      corresponding to the SHC 3' UTR from both loci and have mapped cosmids by
      fluorescence in situ hybridization. The human SHC gene maps to the proximal long
      arm of chromosome 1 and the SHC-related sequence maps to the proximal long arm of
      chromosome 17. A number of cancers have been positioned in the proximal long arm
      of chromosome 1; this is of interest given the oncogenic potential of the SHC
      protein.

PMID- 7635485
TI  - Two novel missense mutations in the cystathionine beta-synthase gene in
      homocystinuric patients.
AB  - Direct sequencing of the coding region of the cystathionine beta-synthase (CBS)
      gene in two homocystinuric patients revealed the presence of two novel missense
      mutations. The first mutation, a 1111G-->A transition, resulted in the
      substitution of the evolutionary conserved valine-371 by a methionine residue
      (V371M) and created a new NlaIII restriction site. The second mutation, a G-->A
      transition at base-pair 494, resulted in an amino acid change from cysteine to
      tyrosine (C165Y) and abolished a BsoFI restriction site. Both mutations were
      found in a compound heterozygous state with the previously described 833T-->C
      transition.

PMID- 7635486
TI  - Single atrium, atrioventricular canal/postaxial hexodactyly indicating Ellis-van
      Creveld syndrome.

PMID- 7635487
TI  - Rapid decline in penicillinase-producing Neisseria gonorrhoeae in Hong Kong
      associated with emerging 4-fluoroquinolone resistance.
AB  - OBJECTIVE--To study the changes in penicillinase-producing (PPNG) and high-level
      tetracycline resistant (TRNG) Neisseria gonorrhoeae isolated in Hong Kong
      associated with emerging quinolone resistance (QRNG) over a two year period from
      November 1992 to October 1994. MATERIALS AND METHODS--Four thousand and eighty
      six strains of Neisseria gonorrhoeae isolated, of which 432 were PPNG, were
      examined for susceptibilities to penicillin and tetracycline by an agar dilution
      method using the breakpoint minimum inhibitory concentrations (MICs) of 1 and 10
      mg/1 respectively. Ofloxacin susceptibility was done using 0.1 and 1 mg/l.
      Penicillinase production was detected by performing the chromogenic cephalosporin
      nitrocefin test on all penicillin resistant (MIC > 1 mg/l) strains. RESULTS-
      Three thousand and eighty (75.4%) and 79 (1.9%) strains were found to be
      penicillin resistant and TRNG (MIC > 10 mg/l) respectively. Sixty-nine strains
      (1.7%) were resistant to both, of which 54 (1.3%) were PPNG. Three strains were
      multiply-resistant to penicillin, tetracycline and ofloxacin; however, none was
      PPNG. While the percentage of penicillin resistant strains remained stable (mean
      75.5%, SD 7.0), TRNG decreased from 4.5% to 2.1%. The most dramatic change was
      the sharp decline of PPNG from 25.5% in January 1993 to 4.3% in October 1994,
      concurrent with a linear increase in strains with ofloxacin MIC > 0.1 mg/l.
      Significant clinical failure was seen in strains having ofloxacin MIC > 1 mg/l
      (QRNG), which increased drastically from 0.5% to 10.4% during the study period.
      Selection against PPNG and TRNG strains appeared to occur only when fully
      quinolone-susceptible strains first become less susceptible (MIC > 0.1 mg/l), but
      not when these less susceptible strains become fully resistant (MIC > 1 mg/l).
      CONCLUSION--PPNG is now no longer hyperendemic in Hong Kong. Emergence of QRNG is
      associated with rapid decline of both PPNG and TRNG. This is the first report of
      plasmid-curing effect of the 4-fluoroquinolones occurring on an ecological scale.

PMID- 7635488
TI  - Resolution of clonal subgroups among Neisseria gonorrhoeae IB-2 and IB-6 serovars
      by pulsed-field gel electrophoresis.
AB  - OBJECTIVE: Analysis of macrorestriction patterns by PFGE to resolve the
      relatedness of clonal subgroups amongst N gonorrhoeae IB-2 and IB-6 serovar
      strains. MATERIALS AND METHODS: Nineteen IB-2 and eight IB-6 serovar strains that
      differed in either auxotype or penicillin sensitivity were isolated over a two
      and a half-year period from patients attending several STD clinics in Sydney.
      During this period, a major clone, Wt/IB-2 (FS), established on epidemiological
      grounds, was circulating amongst homosexual males. The genetic relation of this
      major clone to the other strains present in the community was determined by
      pulsed-field gel electrophoretic (PFGE) analysis of DNA restriction fragments.
      Genomic DNA from the 27 isolates were prepared, digested with SpeI and BglII and
      the restriction patterns were analysed by contour-clamped homogeneous electric
      field electrophoresis (CHEF) in a CHEF DRIII equipment. RESULTS: Phenotypic
      characterisation of the 27 isolates by the combined use of auxotype, serological
      characterisation and penicillin sensitivity indicated the presence of subgroups
      within each of the two serovars. In the present study, PFGE analysis of SPeI and
      BglII-generated genomic DNA restriction patterns from six of the ten Wt/IB-2 (FS)
      correlated well with phenotypic characterisation of this major clone. Four of the
      ten Wt/IB-2 (FS) were found to be clonally-derived variants of this major clone
      as minor genome variations (less than 3 DNA fragments) were observed. Distinct
      clones were represented by three Wt/IB-2 (LS) isolates as the DNA fingerprints
      generated from these were unrelated to the major clone. Analysis of PFGE patterns
      of 6 Pro/IB-2 isolates showed that one was genotypically identical to the major
      clone, two were clonal variants and three had significantly different patterns to
      indicate that they were genotypically unrelated. Wt/IB-6 isolates had
      heterogenous PFGE patterns that were clearly unrelated to the Wt/IB-2 serovar
      strains. Within the IB-6 serovar, there were three isolates with the Wt/IB-6 (FS)
      phenotype that could be considered as clonal variants whilst the rest were
      genotypically distinct. CONCLUSIONS: PFGE analysis of macrorestriction patterns
      generated from SpeI- and BglII-cleavage of genomic DNA has enabled the
      establishment of clonal origins of strains present in the Sydney community during
      the period of study. The delineation of strains belonging to major A/S groups by
      PFGE analysis presents a clearer epidemiological picture than phenotypic
      characterisation alone.

PMID- 7635489
TI  - Rectal gonorrhoea as an independent risk factor for HIV infection in a cohort of
      homosexual men.
AB  - OBJECTIVE: To determine whether certain sexually transmitted diseases are
      independent risk factors for HIV transmission in a cohort of homosexual men.
      METHODS: Eligible cases were identified as those who had seroconverted between
      November 1982 and November 1990. Two persistently HIV-seronegative control
      participants were randomly selected for each case from all participants who
      remained seronegative in November 1990. For cases, risk factor data were taken
      from an index visit which was defined as the first seropositive visit, while for
      controls these data were obtained from a matched visit which occurred within two
      months of the index visit for the corresponding case. Mantel-Haenszel methods and
      logistic regression were used to compare differences in risk factors for
      seroconversion between cases and controls. RESULTS: A total of 125 cases and 250
      controls were eligible for this study. Cases were significantly more likely to
      have had reported any gonorrhoea (17% versus 6%; OR = 2.94; 95% CI: 1.51-5.73) or
      syphilis (7% versus 2%; OR = 3.78; 95% CI: 1.33-10.79) than controls during the
      seroconversion period. Multivariate logistic regression revealed rectal
      gonorrhoea to be independently associated with risk of seroconversion (odds ratio
      = 3.18; p = 0.044), whereas urethral gonorrhoea (p = 0.479) and pharyngeal
      gonorrhoea (p = 0.434) were not after inclusion of rectal gonorrhoea. In
      addition, the following variables were also shown to exert an independent effect
      on seroconversion: frequency of anal intercourse, use of illicit drugs, number of
      male sexual partners, and lack of a post-secondary education. CONCLUSIONS: In
      this observational study, rectal gonorrhoea was found to be associated with HIV
      seroconversion after adjustment for a number of HIV risk factors. We cannot rule
      out that rectal gonorrhoea was not directly associated with HIV infection but
      rather with other residual lifestyle factors not fully adjusted for in the
      analysis. However, the relationship with gonococcal involvement of a specific
      anatomic site lends support to a biological association between gonorrhoea and
      HIV infection, rather than to alternative non-biologic explanations. Our findings
      are consistent with previous studies reporting an association between HIV
      infection and non-ulcerative sexually transmitted diseases. Such a direct
      association might be explained by postulating that gonorrhoea results in inflamed
      rectal mucosa and compromised epithelial integrity, thereby predisposing an
      individual to subsequent HIV infection.

PMID- 7635490
TI  - Sexually transmitted diseases including HIV infection in women with Bartholin's
      gland abscesses.
AB  - OBJECTIVES: The aim of this study was to establish the prevalence of sexually
      transmitted infections including human immunodeficiency virus (HIV) infection in
      women with Bartholin's gland abscess. SETTING: Gynaecology Clinic of King Edward
      VIII Hospital, a large urban, referral hospital for the province of Kwa-Zulu
      Natal, serving an underprivileged population. METHODS: Thirty consecutive women
      presenting with unruptured Bartholin's gland abscesses were studied. Prior to
      surgical drainage, aspirates from the abscess cavity and swab specimens from the
      vagina and endocervix were collected for microbiological investigations. In
      addition peripheral venous blood samples were obtained for syphilis and HIV
      antibody testing. RESULTS: Antibody to HIV was detected in 9 of the 30 (30%)
      patients studied. Recognised sexually transmitted pathogens were detected in both
      aspirates and endocervical specimens: Chlamydia trachomatis was detected in 3
      aspirate and 2 endocervical specimens whilst Neisseria gonorrhoeae was cultured
      in 5 aspirate and 7 endocervical specimens. When comparing microorganisms
      isolated from HIV antibody positive and negative women, only Bacteroides species
      yielded a significantly higher growth (p = 0.01) in the antibody positive women.
      CONCLUSION: Our findings show that women with Bartholin's gland abscesses have a
      high prevalence of HIV antibody. Furthermore, this is the only study that
      demonstrates a role for C trachomatis in the aetiology of Bartholin's gland
      abscesses. Health workers should be aware of the need for appropriate
      counselling, and comprehensive treatment of sexually transmitted infections
      including C trachomatis in women with Bartholin's gland abscesses.

PMID- 7635491
TI  - The silent suffering women--a population based study on the association between
      reported symptoms and past and present infections of the lower genital tract.
AB  - OBJECTIVES: To assess the prevalence of lower genital tract symptoms and the
      association between reported symptoms and past and present signs of sexually
      transmitted diseases (STD) in young women. DESIGN: All women belonging to the 19
      , 21-, 23- and 25-year age cohorts and living in the catchment area of the
      community health centre, were invited by mail to take part in a population-based
      study. The participants answered a structured questionnaire and a gynaecologic
      examination was performed. Samples for wet smear, cervical Pap smear, HPV DNA
      determination and Chlamydia trachomatis culture were taken at the gynaecologic
      examination. The presence of genital warts was noted. A blood sample was analysed
      for antibodies against C trachomatis and HSV-2. SETTING: The community health
      care centre was located in Umea, a city in Northern Sweden. RESULTS: Of the 886
      women who were eligible, 611 (70%) participated in the investigation. One out of
      four women reported symptoms from the lower genital tract. The most commonly
      reported symptoms were itching, followed by discharge, and soreness. The most
      commonly reported STD was C trachomatis (15%). The most prevalent present STD was
      HPV infection (20%) whereas C trachomatis infection could be isolated from 2.7%
      of the women. Antibodies against C trachomatis and HSV-2 were present among 22%
      and 6% of the women, respectively. There was a significant correlation between
      the women's complaint of vaginal discharge and previous C trachomatis infection,
      lack of lactobacilli and presence of leucocytosis in wet smear. CONCLUSIONS: We
      have in a population-based study of young healthy women found that one out of
      four women had some kind of lower genital tract complaint. Itching was the most
      commonly reported symptom and was associated with pseudohyphae and acetowhite
      patches. Reported vaginal discharge and soreness were associated with the history
      of a past C trachomatis infection and signs of a disturbed vaginal flora.

PMID- 7635493
TI  - Use of the polymerase chain reaction for the detection of Chlamydia trachomatis
      in clinical specimens and its comparison to commercially available tests.
AB  - A polymerase chain reaction (PCR) was developed to detect Chlamydia trachomatis
      in genital tract specimens. Two sets of primers for the PCR were used; one set
      amplifies a region of the plasmid present in all C trachomatis strains and the
      other amplifies a conserved region of the genome coding for the major outer
      membrane protein. The sensitivity of these PCRs were compared with each other,
      and with the sensitivities of antigen ELISA, Clearview and culture. Southern
      blotting and probing was used to increase sensitivity of detection.

PMID- 7635492
TI  - Lower genital tract infections in infertile Nigerian women compared with
      controls.
AB  - OBJECTIVE: To investigate the possibility that infertile Nigerian women have a
      higher rate of cervical colonisation with pathogenic and facultative organisms
      than fertile controls. DESIGN: The prevalence of common microorganisms in the
      vagina and endocervical canals of infertile women was compared with that of
      pregnant controls. SETTING: The Obafemi Awolowo University Hospital Maternity
      Centre. SUBJECTS: 92 infertile women were compared with 86 pregnant controls.
      MAIN OUTCOME MEASURES: rates of isolation of Neisseria gonorrhoeae, Candida
      albicans, Trichomonas vaginalis and other facultative organisms in cases and
      controls. RESULTS: The rate of isolation of Neisseria gonorrheae was 17.4% among
      infertile women compared with 10.5% in the group of pregnant women (p > 0.05).
      There was no significant difference between the groups in the rate of isolation
      of Candida albicans, Trichomonas vaginalis and other facultative organisms. High
      rates of isolation of microorganisms were observed in both groups. However, women
      with secondary infertility had higher rate of carriage of Neisseria gonorrheae,
      Candida albicans and Staphylococcus aureus as compared with women with primary
      infertility. Nearly 15% of infertile women had previous episodes of pelvic
      inflammatory disease and 26% had had induced abortions. A positive history of
      vaginal discharge was a poor predictor of vagina and endocervical carriage of
      microorganisms. CONCLUSIONS: High rates of pathogenic organisms exist in the
      lower genital tract of infertile women and controls. Women with secondary
      infertility are more likely to have pathogenic organisms than women with primary
      infertility. A policy of routinely screening women for lower genital tract
      infections should be pursued in this population because of the high rate of
      infection.

PMID- 7635494
TI  - Sexual behaviour and sexually transmitted diseases in Dutch marines and naval
      personnel on a United Nations mission in Cambodia.
AB  - OBJECTIVES: To determine the sexual risk behaviour and the incidence of sexually
      transmitted diseases (STD) among Dutch marines and naval personnel during a
      United Nations (UN) deployment. METHODS: Surveillance by post deployment
      questionnaire, administered to 2289 persons in three successive battalions who
      served for 6 months on a UN deployment in Cambodia during June 1992-November
      1993. On site the medical history of all individuals was kept up to date in a
      database. All personnel received extra education on STD prevention prior to
      deployment. Condoms were freely obtainable during deployment. RESULTS: 1885
      persons (82%) handed in the questionnaire of whom 842 (45%) reported to have had
      sexual contacts with prostitutes or local population. Being younger and single
      were independent risk factors for having contact. Out of these 842 persons, 750
      (89.1%) reported condom use at all times, while 82 (9.7%) reported inconsistent
      use and 10 persons (1.2%) reported not to have used condoms. Risk factors for
      inconsistent and non use were being 40 years or older and a higher number of
      contacts. From the 832 (750 + 82) condom users, 248 (30%) reported condom
      failure. Risk factors for failure were: inconsistent condom use, having had more
      than six contacts and being in the second battalion. The patient recording
      database showed 43 STD cases registered in the total population of 2289 persons
      (1.9%). CONCLUSIONS: A low STD incidence was found despite a considerable number
      of reported sexual contacts. The reported condom use was high but the failure
      rate was considerable and needs further attention.

PMID- 7635496
TI  - Sexual attitudes, preferences and infections in Ancient Egypt.
AB  - This socio-sexual review of Ancient Egyptian society aims to increase awareness
      that the prevalence of sexually transmitted diseases (STDs) is largely determined
      by the way a society is structured and how that structure functions. The
      prevalence of STDs in Ancient Egypt has been found to be low. This state of
      affairs was maintained for centuries. Although the structure of their society was
      rigidly hierarchical, Egyptian people made it function in an acceptable way. What
      might be learned is concerned more with prevention than cure. Whether this has
      any relevance today is discussed.

PMID- 7635495
TI  - Neutrophil enzymes in urine for the detection of urethral infection in men.
AB  - OBJECTIVES: To determine if assaying the neutrophil enzymes, neutrophil elastase
      (NE) and myeloperoxidase (MPO) in the urine of men attending a genitourinary
      medicine clinic could identify those with Neisseria gonorrhoeae or Chlamydia
      trachomatis infections, and those with urethritis (with or without an identified
      infection with either organism), and to compare the new assays with the
      performance of the leucocyte esterase test (LET). METHOD: 100 men had urethral
      specimens taken for Gram-stained urethral smear, culture for N gonorrhoeae, and
      for C trachomatis testing by enzyme immunoassay. First-voided urines were tested
      for leucocyte esterase by commercial dipstick (positives were defined as greater
      than "trace") and then frozen at -20 degrees C prior to being assayed for NE and
      MPO. RESULTS: Five patients had gonorrhoea, six had chlamydia and none had both.
      Evidence of urethritis (> 5 polymorphonuclear leucocytes in four x 1000 fields)
      was found in 29 men. The results of the urine assays showed MPO levels to be non
      discriminatory; however NE levels were significantly elevated in patients with
      proven infection or urethritis or both. Using NE values from men with no
      infection or urethritis an upper limit for normal was defined. Utilising this,
      the sensitivity of the elastase assay was calculated and found to be superior to
      the sensitivity of LET for detecting proven infection (64% vs 36%) and urethritis
      (52% vs 31%). CONCLUSIONS: Further studies of neutrophil elastase in the
      pathogenesis, diagnosis and treatment of urethritis are indicated.

PMID- 7635497
TI  - Disseminated cryptococcal infection despite treatment for cryptococcal
      meningitis.

PMID- 7635498
TI  - Genital warts: just a nuisance?

PMID- 7635499
TI  - Warts in the oral cavity.

PMID- 7635500
TI  - Urticarial manifestations associated with herpes simplex virus type 2.

PMID- 7635501
TI  - Azithromycin and syphilis.

PMID- 7635502
TI  - Syndromic management of genital ulcer disease--a critical appraisal.

PMID- 7635503
TI  - An unusual cause of incontinence.

PMID- 7635504
TI  - Factors affecting reattendance rates at genitourinary medicine clinics.

PMID- 7635505
TI  - Trichomonas vaginalis transmission in a family.

PMID- 7635506
TI  - Asthma in an AIDS patient with Norwegian scabies induced by bathing.

PMID- 7635507
TI  - Diagnosis of gonorrhoea by microscopy.

PMID- 7635508
TI  - It could be more serious than you think!

PMID- 7635509
TI  - Barrier methods of contraception.

PMID- 7635510
TI  - STD/HIV control in Malawi.

PMID- 7635511
TI  - Protection against Leishmania major infection in genetically susceptible BALB/c
      mice by gp63 delivered orally in attenuated Salmonella typhimurium (AroA- AroD-).
AB  - The gene encoding the Leishmania major (L. major) promastigote surface
      glycoprotein, gp63, was introduced into the Salmonella typhimurium (S.
      typhimurium) aroA- aroD- live oral vaccine strain BRD509 and expressed under the
      control of a constitutive tac promoter in plasmid pKK233-2. This construct
      (GID101) expressed gp63 in vitro and was used to immunize highly susceptible
      BALB/c mice by the oral route. The plasmid was relatively stably inherited by
      bacteria growing or persisting in the mesenteric lymph nodes of immunized mice.
      Mice immunized with GID101 developed significant resistance against a challenge
      infection with L. major compared to controls immunized with BRD509 alone. Spleen
      and lymph node cells from immunized mice developed a strong in vitro
      proliferative T-cell response to killed or live L. major. The activated T cells
      secreted interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) which was
      abrogated by treatment with anti-CD4 but not with anti-CD8 antibody. The cells
      did not produce detectable levels of interleukin-4 (IL-4). The immunized mice
      also produced significant amounts of leishmanial specific IgG2a antibody but did
      not develop delayed-type hypersensitivity (DTH) to live parasites. No IgG1
      antibody was detected. These data therefore demonstrate that gp63 gene delivered
      orally by a vaccine strain of S. typhimurium can preferentially induce the
      development of Th-1 subset of CD4+ T cells and protective immunity in the highly
      susceptible BALB/c mice.

PMID- 7635512
TI  - Down-regulation of transforming growth factor-beta gene expression by antisense
      oligodeoxynucleotides increases recombinant interferon-gamma-induced nitric oxide
      synthesis in murine peritoneal macrophages.
AB  - Increasing evidence indicates that the production of nitric oxide (NO) by
      inducible NO synthase (iNOS) is tightly regulated. Transforming growth factor
      beta (TGF-beta) is a family of multifunctional peptides secreted during
      macrophage activation, but several lines of evidence suggest that TGF-beta is
      selectively suppressive for macrophage NO production. We therefore reasoned that
      a strategy employing oligodeoxynucleotides (ODN) complementary to TGF-beta mRNA
      (antisense ODN) might increase NO production in interferon-gamma (IFN-gamma)
      treated murine peritoneal macrophages. To evaluate this concept, we tested the
      effects of antisense ODN targeted to TGF-beta mRNA (25-mer ODN complementary to
      TGF-beta mRNA sequences) by introducing them into the medium of cultured
      macrophages. Phosphorothioation of ODN was employed to retard their degradation.
      Antisense ODN had no effect on NO production by itself, whereas IFN-gamma alone
      had a modest effect. When antisense ODN were used in combination with IFN-gamma,
      there was a marked cooperative induction of NO production. These effects of
      antisense ODN were associated with decreased TGF-beta expression in activated
      macrophages. However, sense ODN had no effect. Adding anti-TGF-beta antibodies to
      the IFN-gamma-treated macrophages mimicked the positive effect of antisense ODN
      on NO production. In addition, the effects of either antisense ODN or anti-TGF
      beta antibodies were blocked by adding exogenous TGF-beta in cultured
      macrophages. These results indicate that the generation of TGF-beta by activated
      macrophages provides a self-regulating mechanism by which the temporal and
      perhaps spatial production of NO, a reactive and potentially toxic mediator, can
      be finely regulated.

PMID- 7635513
TI  - In vitro production of interleukin-4 and interferon-gamma by lymph node cells
      from BALB/c mice infested with nymphal Ixodes ricinus ticks.
AB  - In this study we compared the ability of lymphocytes taken from axillary and
      brachial lymph nodes of BALB/c mice that had been infested once three times with
      15 nymphal Ixodes ricinus ticks, to produce interleukin-4 (IL-4) and interferon
      gamma (IFN-gamma) after in vitro stimulation with concanavalin A (Con A). They
      released high levels of IL-4 and low levels of IFN-gamma. An increase of IFN
      gamma between the first and the third tick infestation was observed. Salivary
      gland extracts from female I. ricinus ticks induced specific in vitro
      proliferation of lymphocytes from infested mice. IL-4 production was correlated
      with the salivary gland extracts' ability to stimulate tick-specific lymphocyte
      proliferation. Its levels remained high from the first to the third infestation.
      IFN-gamma production was not necessarily associated with tick salivary gland
      antigen stimulation. In BALB/c mice, anti-tick immune response induction is
      regional and the contribution of other similar secondary lymphoid organs is
      negligible. Only cells from the lymph nodes which drained the tick-fixation site
      proliferated in vitro in the presence of tick antigens, and when stimulated with
      Con A produced IL-4 and IFN-gamma.

PMID- 7635514
TI  - Tumour necrosis factor-alpha interacts with laminin and functions as a pro
      adhesive cytokine.
AB  - Certain cytokines, chemokines and growth factors interact with components of the
      extracellular matrix (ECM) and, in particular, sulphated polysaccharides and
      proteoglycans. Recently, we demonstrated that tumour necrosis factor-alpha (TNF
      alpha), an inflammatory cytokine, can bind fibronectin (FN), a cell-adhesive
      glycoprotein of the ECM, and that TNF-alpha bound to FN enhances the binding of T
      cells to the glycoprotein. In the present study, we studied the interactions of
      TNF-alpha and laminin (LN), another glycoprotein present in basement membranes
      and extracellular matrices. 125I-labelled TNF-alpha was found to bind to
      immobilized LN, and more avidly to the E1 and P1 fragments of LN, which contain
      its integrin- and non-integrin-dependent cell-adhesive sites, suggesting that
      cryptic TNF-alpha-binding sites are exposed upon proteolytic fragmentation of LN
      by enzymes such as elastase or pepsin. The bound cytokine did not dissociate from
      the LN and its fragments during a 24-hr period, indicating that in vivo LN can
      serve to restrict TNF-alpha adjacent to inflammatory sites. The LN-associated TNF
      alpha retained at least some of its biological activities, since both diffusible
      and, to a greater extent, LN-bound TNF-alpha elevated the beta 1-integrin
      dependent adhesion to LN of phorbol ester-activated human CD4+ T cells. Thus, LN
      and TNF-alpha may act in concert to transmit synergistic activating signals to
      infiltrating leucocytes, and thereby regulate immune cell reactions in
      extravascular inflammatory tissue.

PMID- 7635515
TI  - Mannose binding protein is involved in first-line host defence: evidence from
      transgenic mice.
AB  - Mannose binding protein (MBP) is a calcium-dependent C-type lectin secreted by
      the liver which seems to be an important component of innate or natural immunity.
      We have investigated the effects of Candida albicans and thioglycolate injection
      into transgenic mice bearing the human MBP gene. The transgenes contained a 15 kb
      fragment of the MBP gene which included the complete coding sequence. Northern
      blot hybridization showed human MBP mRNA transcripts in the liver of two
      transgenic lines with low and high copy number respectively. Western blot
      analysis showed the presence in serum of human MBP which associated into the
      higher multimeric forms which are capable of activating complement. Enzyme-linked
      immunosorbent assays (ELISA) showed that serum human MBP concentrations in the
      transgenes (1.90 +/- 0.16 mg/l, mean +/- SEM) were about twice as high as the
      levels in man. The serum concentration of MBP A, which is the mouse homologue of
      MBP, (13.9 +/- 0.45 mg/l) was about seven times that of human MBP. Intravenous
      injection of Candida albicans caused the serum human MBP level to fall by more
      than 50% in the first hour and then slowly recover, but it did not return the
      initial value by 72 hr. Candida injection caused a 25% fall in serum mouse MBP A
      in the first hour which then rose to supranormal levels by 72 hr. Following
      Candida injection mouse MBP A mRNA concentrations increased over 72 hr in
      contrast to human MBP mRNA which remained constant in both transgenic lines.
      These data indicate that the human MBP gene fragment in the transgene did not
      include the regulatory elements of the gene. Total haemolytic complement activity
      and C3 concentrations also fell immediately after Candida and thioglycolate
      injection while the concentrations of mannose specific immunoglobulin G (IgG) and
      immunoglobulin M (IgM) did not fall. The data indicate that mannose binding
      protein plays an important role in the initial stages of defence against
      infection which, in this model, is quantitatively greater than that of mannose
      specific IgG and IgM antibodies. Mannose binding protein is probably most
      important in defense of previously unexposed and non-immune hosts.

PMID- 7635516
TI  - Modulation of B-cell abnormalities in lupus-prone (NZB x NZW)F1 mice by normal
      bone marrow-derived B-lineage cells.
AB  - (NZB x NZW)F1(NZB/WF1) mice spontaneously develop an autoimmune disease
      characterized by abnormality of haemopoietic stem cells. The present study
      examined a possible regulatory cell interaction between NZB/WF1 and normal bone
      marrow cells using radiation-induced chimeras. We demonstrated that the ability
      of NZB/WF1 bone marrow cells to transfer the typical disease with
      hypergammaglobulinemia including autoantibodies into lethally irradiated normal
      recipients was prevented by cotransfer of bone marrow from normal CBA/J mice but
      not from xid CBA/N mice carrying a selective defect in B-cell function. Flow
      cytometric analysis revealed that the generation of NZB/WF1 cells was reduced in
      the mixed chimeras given CBA/J but not CBA/N bone marrow cells. Interestingly,
      radiation chimeras reconstituted with a mixture of NZB/WF1 bone marrow and CBA/J
      splenic B cells did not show elevation of serum immunoglobulin levels, although
      most of the spleen cells were dominated by NZB/WF1 cells. On the other hand,
      NZB/WF1 B cells maturated in vivo in the presence of CBA/J bone marrow or splenic
      B cells lost the hyper-responsiveness to lipopolysaccharide (LPS) in the
      autoantibody production in vitro. These results suggest that radiosensitive
      normal B-lineage cells have the regulatory activity to ameliorate the
      hypergammaglobulinemia of NZB/WF1 mice by reducing the generation of NZB/WF1 B
      cells and/or by correcting their hyper-responsiveness, and that NZB/WF1 mice may
      have a defect(s) in the regulatory cell function. In addition, CBA/J splenic B
      cells were shown to modulate the B-cell abnormality even when injected into non
      irradiated NZB/WF1 mice manifesting autoimmunity.

PMID- 7635517
TI  - Effect of the parasite enzyme, hypodermin A, on bovine lymphocyte proliferation
      and interleukin-2 production via the prostaglandin pathway.
AB  - The immune function of cattle infected with a primary infestation of Hypoderma
      lineatum is impaired during the first instar migration of the larvae. Hypodermin
      A (HA) is an enzyme secreted by the larvae that is implicated in
      immunosuppression. The response of bovine peripheral blood mononuclear cells
      (PBMC) to HA was examined in this study. HA blocked their proliferation in
      response to phytohaemagglutinin (PHA) and its effect was enhanced when cells were
      preincubated with HA before activation. This suggests that HA affects the
      lymphocyte commitment to blastogenesis during the early stages of their
      activation. HA also markly reduced the production of interleukin-2 (IL-2) in PHA
      stimulated bovine PBMC cultures. Furthermore, indomethacin, which inhibits
      prostaglandin (PG) synthesis, blocked the immunosuppressive effect of HA on the
      PBMC proliferative response. The concentration of PGE2 in medium of PBMC or PMA
      stimulated monocyte cultures was increased by incubation with HA. Thus, the HA
      appeared to act by reducing IL-2 production via a prostaglandin-dependent
      pathway.

PMID- 7635518
TI  - An aberrant splicing using a 3' cryptic splice site within the CH1 exon induces
      truncated mu-chain production.
AB  - AT8--1-12--5-1, an Abelson virus-transformed immature B-cell line, produced
      truncated mu-chains. Sequencing analysis of the mu-expressed allele revealed that
      the variable region was an out-of-frame VH7183-DSP2-JH3 complex. Two cDNA clones
      (5-1 cDNA1 and 5-1 cDNA2) derived from the transcripts of the mu-expressed allele
      were cloned and sequenced. Sequencing analysis of 5-1 cDNA1 revealed that the
      VH7183-DSP2-JH3 sequence jointed to the CH1 exon at 136 bp, 3' from the 5' end of
      the CH1 exon, resulting in the change of the reading frame from out-of-frame to
      in-frame. On the other hand, sequencing analysis of 5-1 cDNA2, which appeared to
      have derived from intron-containing premature mRNA, revealed that the J-C intron
      sequence joined to the CH1 exon at 110 bp 3' from the 5' end of the CH1 exon,
      indicating the deletion of 109 bp including the 3' splice site of the CH1 exon.
      These results demonstrate that the deletion of the authentic 3' splice site of
      the CH1 exon induced activation of the cryptic splice site within the CH1 exon.
      This was followed by splicing of the variable region to the CH1 exon at the
      cryptic splice site at 136 bp 3' from the 5' end of the CH1 exon, resulting in
      the change of the reading frame from out-of-frame to in-frame, followed by the
      truncated mu-chain production.

PMID- 7635519
TI  - Defects in the regulation of anti-DNA antibody production in aged lupus-prone
      (NZB x NZW)F1 mice: analysis of T-cell lymphokine synthesis.
AB  - (NZB x NZW)F1 (B/W) mice spontaneously develop a lupus-like syndrome
      characterized by an increased level of autoantibodies in old mice. We analysed
      the role of T cells in the regulation of anti-DNA antibody production by B cells
      in vitro as a function of age. In cultures of old mouse T and B cells, IgG and
      IgM anti-DNA antibodies were synthesized at high levels, in contrast to
      consistently lower amounts, particularly of IgG, measured in cultures of young
      mouse cells. Addition of young mouse T cells to old B cells inhibited IgG, but
      not IgM, anti-DNA production, whereas T cells from old mice stimulated IgG
      synthesis by young mouse B cells. Addition of supernatants harvested from
      concanavalin A (Con A)-stimulated T cells to B-cell cultures induced similar
      effects. Therefore, we evaluated possible modifications of lymphokine synthesis
      compared to that of the healthy NZW parent. T cells from old mice were able to
      secrete normal levels of interferon-gamma (IFN-gamma) and interleukin (IL)-10;
      however, secretion of IL-2 and IL-4 was dramatically decreased. Semi-quantitative
      polymerase chain reaction analysis of constitutive RNA messengers showed
      increased IFN-gamma levels in young and old B/W mice, and normal IL-10 mRNA
      levels in young and higher levels in old mice. Constitutive IL-2 and IL-4 mRNA
      were detected only after Con A stimulation and their levels decreased in old
      compared to young B/W mice; in particular IL-2 mRNA was considerably lower in old
      B/W than in control NZW mice. Taken together, these results suggest that, despite
      constitutive T-cell abnormalities, young B/W mice are able partially to control
      their lymphokine production, whereas aged mice exhibit a deficient synthesis,
      associated with an increased capacity to produce IFN-gamma.

PMID- 7635520
TI  - Functional analysis of the effects of a fully humanized anti-CD4 antibody on
      resting and activated human T cells.
AB  - A fully humanized anti-CD4 antibody was studied for its effects on resting and
      activated CD4 T cells. Whereas the antibody was poorly lytic, it induced dramatic
      down-modulation of CD4 expression on both types of cell. In order to down
      modulate CD4 on resting, normal CD4 T cells there was an absolute requirement for
      FcR-mediated cross-linking of the anti-CD4 antibody, and only CD4 levels were
      affected. When activated cloned T-cell lines were studied there was no
      requirement for cross-linking and several other cell surface markers were also
      affected. Although the total cellular CD4 was reduced in the down-modulated
      cells, as judged by Western blot analysis, that CD4 which remained was associated
      with p56lck. The results are discussed in relation to the potential use of
      humanized anti-CD4 antibodies in the therapy of autoimmune disease and the choice
      of antibody isotype for such a therapeutic antibody.

PMID- 7635522
TI  - Superantigens and conventional antigens induce different responses in alpha beta
      T-cell receptor transgenic mice.
AB  - While superantigens such as staphylococcal enterotoxin B (SEB) have been shown to
      induce both clonal deletion and clonal anergy, it is still not known why
      tolerance rather than memory is induced. To address this issue, we tested the
      proliferative capacity of T cells from ovalbumin (OVA)-specific alpha beta T-cell
      receptor transgenic mice primed with either SEB emulsified in complete Freund's
      adjuvant (CFA) or with OVA peptide, the specific antigen, in CFA. By contrast
      cells from mice primed with SEB in CFA appeared to be anergic in that they were
      hyporesponsive to OVA peptide as well as to SEB. The anergic cells could respond
      to phorbol myristate acetate (PMA) and ionomycin, suggesting that a proximal
      signal transduction step was affected. Cells from transgenic mice primed with OVA
      peptide and CFA were not anergic and in fact displayed an enhanced response when
      they were challenged with OVA in vitro. Thus, when the two antigens are
      emulsified in CFA and then injected subcutaneously, they behave very differently:
      the superantigen SEB induces anergy whereas the conventional antigen OVA induces
      a memory type of response.

PMID- 7635521
TI  - Herpes simplex virus-specific human cytotoxic T-cell colonies expressing either
      gamma delta or alpha beta T-cell receptor: role of accessory molecules on HLA
      unrestricted killing of virus-infected targets.
AB  - Previous studies have demonstrated that herpes simplex virus-1 (HSV-1)-infected
      mononuclear cells are able to stimulate autologous peripheral blood mononuclear
      cells (PBMC) of immune donors and to activate HSV-specific cytotoxic T
      lymphocytes (CTL) expressing either gamma delta or alpha beta T-cell receptors
      (TCR). In the present report characterization of 10 gamma delta+ and six alpha
      beta+ HSV-specific cytotoxic T-cell colonies (TCC) is described. Cytotoxic
      colonies were derived from HSV-induced cell lines of three donors who, in
      previous experiments, had shown a prevalence of gamma delta+ or alpha beta+
      effector cells. HSV-1 induced cell lines obtained from gamma delta responders
      included more than 80% of cells expressing V gamma 9/delta 2 TCR V region chains.
      gamma delta+ TCC also expressed V gamma 9/delta 2 molecules. alpha beta+ TCC all
      expressed CD8 antigen, while only one of 10 gamma delta+ TCC was CD8+, the others
      being CD4/CD8-double negative. The cytotoxic response of HSV-specific TCC was HLA
      unrestricted; nevertheless CD8+ TCC were dependent on the expression of HLA class
      I on the surface of target cells to mediate cytolytic activity, while CD8- TCC
      were not. Blocking experiments with monoclonal antibody (mAb) specific for
      lymphocyte function-associated antigen-1 (LFA-1), which is expressed on all TCC,
      demonstrated that all alpha beta+ TCC and some gamma delta+ TCC also needed the
      interaction between LFA-1 and its ligands to develop cytotoxic activity.
      Altogether our data suggest that HSV-specific CTL may represent a population
      selected by a high concentration of antigen with a broad range of TCR affinities,
      which may play an important role as a first line of defence against HSV
      infection.

PMID- 7635523
TI  - Association of nbl gene expression and glucocorticoid-induced apoptosis in mouse
      thymus in vivo.
AB  - A gene of unknown biological function, nbl, was originally isolated by virtue of
      its abundance in a Namalwa Burkitt Lymphoma cDNA library. nbl expression was
      initially found to be higher in tissues which exhibited internucleosomal DNA
      cleavage characteristic of apoptosis, than in tissues which did not exhibit a
      'DNA ladder'. nbl expression was therefore examined in mouse thymus in vivo, in
      which apoptosis is induced by the glucocorticoid, dexamethasone. nbl expression
      was markedly enhanced by dexamethasone treatment and then sharply decreased prior
      to the occurrence of maximal 'DNA ladder' formation. In contrast, expression of
      myc, which is believed to be involved in apoptosis in other cell systems,
      declined as thymic apoptosis increased. Thymic apoptosis was blocked by the
      transcriptional inhibitor actinomycin D, if administered when nbl expression was
      enhanced, but not before or after the peak of nbl expression. These results
      suggest that nbl expression is associated with thymic apoptosis.

PMID- 7635524
TI  - Depletion of cells of the B lineage in the bone marrow of zinc-deficient mice.
AB  - Though lymphopenia is often noted in malnourished humans and rodents, little is
      known about the effects of suboptimal nutriture on lymphopoietic processes.
      Focusing primarily on cells of the B lineage in the marrow of young adult mice, a
      moderate degree of zinc deficiency (MZD) caused a 43% decline in the proportion
      of nucleated cells bearing B220 with a 91% decline noted among more severely zinc
      deficient mice (SZD). Early B cells (B220+Ig-) were highly sensitive to the
      deficiency, being barely detectable in SZD mice and reduced by almost 60% in MZD
      mice. Immature B cells (B220+IgM+IgD-) were similarly affected, declining 35% to
      80% depending on the degree of the deficiency. In MZD mice, mature B cells
      (IgM+IgD+) exhibited moderate losses, being somewhat resistant. A more profound
      loss in this population was noted for SZD mice. Flow cytometric (FACS) scatter
      profiles indicated that zinc deficiency caused a sharp decline in the proportion
      of small nucleated cells which in the marrow are thought to contain a high
      proportion of developing lymphoid cells. There was a concomitant increase in
      large granular cells that paralleled a substantial increase in the proportion of
      nucleated cells bearing Mac-1 for both MZD and SZD mice. Given the dramatic
      depletion of cells of the B lineage in the marrow created by a deficiency in
      zinc, it is probable that disruptions in lymphopoietic processes in the marrow
      play a key role in the resulting lymphopenia observed in many types of
      malnutrition.

PMID- 7635525
TI  - Presensitization by skin grafting from major histocompatibility complex class I
      or major histocompatibility complex class II deficient mice identifies class I
      antigens as inducers of allosensitization.
AB  - Livers but not hearts are accepted spontaneously without immunosuppression when
      transplanted from B10 (KbAbEbDb) to C3H (KkAkEkDk) mice. Both organs however,
      undergo accelerated rejection in C3H recipients presensitized with B10 skin
      grafts. In this study, we have investigated further the role of functional cell
      surface major histocompatibility complex (MHC class I or class II molecules in
      allosensitization. Skin from transgenic MHC class I (b2mmlUncbcr; AbEb) or class
      II (C2DTM, KbDb) gene 'knockout' mice was grafted onto naive recipients 2-3 weeks
      prior to whole organ transplantation. When C3H hosts were presensitized with skin
      from C2DTM (class II deficient) mice, they promptly rejected (within 4 days)
      subsequently transplanted B10 liver or heart allografts. In contrast,
      presensitization with skin from b2m (beta 2-m mutant; class I deficient) mice did
      not significantly affect the survival of either organ graft. Maximal
      sensitization was established by day 14 after skin grafting and persisted for at
      least 12 weeks. Splenocytes obtained from C3H mice sensitized with skin from B10,
      B6 (KbAbEbDb), or C2DTM but not from b2m mice exhibited an H-2b-specific
      cytolytic response when tested in cell-mediated lymphocytotoxicity assays. Sera
      from C3H mice sensitized with B10 or b2m skin contained high titres of cytotoxic
      activity specifically against H-2b class I. Taken together, these observations
      suggest that in the strain combination studied, MHC class I rather than class II
      molecules play an important role in allosensitization. The results indicate the
      potential importance of avoiding transplantation of organs into recipients of
      secondary grafts from donors that share human leucocyte antigen (HLA) class I
      antigens with the first donor.

PMID- 7635526
TI  - Rat intestinal dendritic cells: immunostimulatory potency and phenotypic
      characterization.
AB  - Dendritic cells (DC) acquire antigens in peripheral tissues, transport them to
      lymph nodes and present peptides to T cells. DC are particularly good activators
      of resting T cells. Murine Langerhans' cells (LC) are efficient at endocytosing
      and processing antigens but are very weak immunostimulators. In culture LC lose
      the ability to process antigen and become potent immunostimulators. Other
      peripheral DC are not well characterized and it is not known if they are
      similarly weak immunostimulators. We isolated DC from rat Peyer's patches (PP)
      and lamina propria (LP) of the small intestine, from intestinal lymph (LDC) and
      mesenteric lymph nodes, and examined their ability to stimulate an allogeneic
      mixed leucocyte reaction (MLR). Freshly isolated LP DC and PP DC could stimulate
      a moderate MLR but fresh LDC were significantly more potent. After overnight
      culture, LDC did not change their potency but DC from LP and PP became as potent
      as LDC. In contrast, fresh lymph node DC stimulated a MLR or oxidative
      mitogenesis as efficiently as LDC. These results show that the weak
      immunostimulation of murine LC is not characteristic of all peripheral DC. We
      compared the phenotypes of DC from different sites before and after culture.
      Different populations of DC show marked phenotypic heterogeneity in the
      expression of surface markers, particularly Thy-1, CD2 and the iC3b receptor. PP
      and LP DC were similar to MLN DC in their expression of markers, but differed
      from LDC. After culture there were marked changes in DC surface marker expression
      and the differences between the populations were reduced. These observations
      suggest that the heterogeneity observed in fresh populations does not signify
      different stages of maturation but may represent activation.

PMID- 7635527
TI  - In vitro infection of human epidermal Langerhans' cells with HIV-1.
AB  - Epidermal Langerhans' cells (LC) from human immunodeficiency virus type-1 (HIV-1)
      infected patients harbour HIV-1 proviral DNA and RNA. In the present study, we
      investigated whether LC from epidermis of normal, HIV-seronegative subjects could
      be infected in vitro with HIV-1. Epidermal cells (EC) spontaneously detached from
      epidermal sheet cultures were enriched for LC (10-25% of CD1a+/CD4+ cells),
      deprived of contaminating T cells and then incubated with HIV-1IIIB. After 24 hr,
      purified LC and LC-depleted EC fractions were obtained by immunomagnetic
      separation. Polymerase chain reaction (PCR) analysis showed the presence of HIV-1
      proviral DNA (gag) only in purified LC. In addition, LC-enriched EC, purified LC,
      LC-depleted EC or the non-permissive cell line, TF-1, the latter having being
      previously challenged with HIV-1IIIB for the same length of time as the EC, were
      co-cultivated with C8166 cells, and the co-cultures assessed for the presence of
      HIV DNA by PCR. Co-cultures of C8166 cells with purified LC or LC-enriched EC
      previously exposed to HIV-1IIIB exhibited a time-dependent increase in HIV
      proviral DNA. In contrast, PCR analysis of C8166 cells co-cultured with either LC
      depleted EC or TF-1 cells gave negative results. Finally, C8166 cells co-cultured
      with HIV-infected LC formed syncytia, showed membrane budding and released
      numerous retroviral particles. The results indicate that LC from normal subjects
      can be infected in vitro with HIV and can transmit infection to myeloid cells.
      This in vitro model may help in understanding the regulation of HIV infection of
      LC.

PMID- 7635529
TI  - Theodore Cooper Memorial Lecture. Kallikreins and kinins. Some unanswered
      questions about system characteristics and roles in human disease.
AB  - Kinins can affect many aspects of cellular function, but their roles in human
      homeostatic mechanisms and disease are just beginning to be understood. In this
      brief review, some of the interesting new observations about kallikrein-kinin
      system characteristics, roles in cell behavior, and aberrancy in diseases of
      relevance to readers interested in hypertension will be discussed. Along the way,
      questions raised by these observations will be posed. They show that we still
      have much to learn about the contributions of kinins to human cardiovascular
      diseases but now have in addition both a strong rationale for asking them and the
      tools to make them operational.

PMID- 7635528
TI  - Ontogeny of rat thymic macrophages. Phenotypic characterization and possible
      relationships between different cell subsets.
AB  - In the present study we combined electron microscopy, immunohistology and primary
      stromal cell cultures to analyse the ontogeny of rat thymic macrophages (M phi)
      in an attempt to clarify the relationships between the different macrophage cell
      subsets described in adult rat thymus. Although phagocytic cells were observed in
      15-day-old fetal thymus, monoclonal antibodies (mAb) which recognize different
      adult macrophage types were unable to identify positive cells until the end of
      embryonic life. However, our in vitro results from primary thymic stromal cell
      cultures of 16-day-old fetal rats, and the phenotyping of enriched thymic CD2-
      cell suspensions, demonstrated that monocyte-like cells which strongly expressed
      major histocompatibility complex (MHC) class II molecules colonized the embryonic
      thymus early, giving rise later to distinct macrophage subsets. During the
      process of maturation, macrophage precursors gradually lost their MHC class II
      expression, acquired other surface markers (CD45, Thy-1, CD25, CD4, etc.) and
      increased the acid phosphatase activity. In this respect, ED1+ macrophages, which
      appeared for the first time in the last stages of embryonic life, consisted of a
      MHC class II molecule-expressing phagocytic cell population, presumably involved
      in the elimination of non-selected cortical thymocytes, and of non-phagocytic
      cells which, in the thymic cortex, might differentiate to ED2+ macrophages
      throughout ED1+ED2lo/med and ED1+ ED2high intermediate cell stages, observed in
      vitro in 16-day-old fetal thymic stromal cell cultures. At the end of embryonic
      life and during the postnatal period the numbers of thymic macrophages increased,
      particularly in the medulla and corticomedullary border (CMZ), and more slowly in
      the thymic cortex. This increase was presumably due to the arrival, through
      perivascular spaces, of new macrophage progenitors, rather than in situ
      proliferation of pre-existent mature macrophages. The possible function of
      different thymic macrophage subsets, as well as the relationships between
      themselves and with their presumptive monocyte-like precursors, are discussed.

PMID- 7635530
TI  - Regulation and differential expression of neutral endopeptidase 24.11 in human
      endothelial cells.
AB  - Neutral endopeptidase 24.11, a membrane-bound metallopeptidase, cleaves, and
      degrades vasoactive peptides such as atrial natriuretic peptide, endothelin,
      angiotensin I, substance P, and bradykinin. Therefore, the presence of this
      metallopeptidase may contribute to the regulation of vascular tone and local
      inflammatory responses in the vascular endothelium and elsewhere. We determined
      neutral endopeptidase in cultured human endothelial cells from different vascular
      beds and studied its regulation by protein kinase C. Neutral endopeptidase was
      detected in all cultured endothelial cell types. Lowest concentrations were
      measured in human endothelial cells from umbilical veins (360 +/- 14 pg/mg
      protein), followed by pulmonary and coronary arteries; higher concentrations were
      found in endothelial cells from the cardiac microcirculation (1099 +/- 73 pg/mg
      protein). Neutral endopeptidase content increased during cell growth but was not
      affected by endothelial cell growth factor or modifications of the growth medium.
      Stimulation of protein kinase C with 1-oleoyl-2-acetyl-rac-glycerol (0.1 to 1
      mumol/L) and phorbol 12-myristate 13-acetate (0.01 to 0.1 mumol/L) induced a time
      and concentration-dependent increase of endothelial cells that was inhibited by
      cycloheximide (5 mumol/L), an inhibitor of protein synthesis. Incubation with
      phospholipase C (1 mumol/L) and thrombin (10 IU/mL) induced upregulation of
      neutral endopeptidase, resulting in 158 +/- 26% and 150 +/- 22% increases,
      respectively, compared with controls. The thrombin effect was inhibited by
      calphostin C (1 mumol/L), an inhibitor of protein kinase C. Endothelial neutral
      endopeptidase is constitutively expressed in endothelial cells from different
      origins and is inducible by thrombin via activation of the protein kinase C
      pathway.

PMID- 7635531
TI  - Nitric oxide and prostaglandins in the prolonged effects of losartan and ramipril
      in hypertension.
AB  - We investigated the role of endogenous nitric oxide, kinins, and prostaglandins
      in the vasodepressor and renal excretory effects of the angiotensin II receptor
      antagonist losartan and the angiotensin-converting enzyme inhibitor ramipril
      administered for 1 week to spontaneously hypertensive rats. To this end, either
      losartan (10 mg/kg per day) or ramipril (2.5 mg/kg per day) was administered in
      drinking water with or without simultaneous administration of (1) the nitric
      oxide synthesis inhibitor Ng-nitro-L-arginine methyl ester (L-NAME, 6 mg/kg per
      day), (2) the cyclooxygenase inhibitor indomethacin (5 mg/kg per day), (3) the
      bradykinin B2 receptor antagonist Hoe 140 (0.5 mg/kg per day SC), or (4) L-NAME
      plus indomethacin. Both losartan and ramipril significantly reduced blood
      pressure as measured by the tail-cuff method. L-NAME increased blood pressure
      when administered solely or in combination with losartan. However, L-NAME
      attenuated the hypotensive effect of ramipril. Indomethacin did not affect blood
      pressure but it reduced the antihypertensive action of losartan and ramipril.
      Indomethacin administration did not potentiate the increase in blood pressure
      induced by L-NAME. However, the concurrent administration of both inhibitors
      almost totally blunted the vasodepressor action of ramipril. By contrast,
      losartan administration in the presence of L-NAME and indomethacin increased
      blood pressure to a level similar to that after losartan plus L-NAME. Hoe 140 did
      not modify either blood pressure or the hypotensive effects of losartan or
      ramipril. Increases in diuresis and water intake were observed during ramipril
      administration. Both effects were blunted only with the concurrent administration
      of L-NAME and indomethacin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7635532
TI  - Renal vasodilation with L-arginine. Effects of dietary salt.
AB  - Infusion of L-arginine, the substrate for nitric oxide synthase, causes renal
      vasodilation. Since dietary salt restriction blunts the renal vasoconstrictor
      response to inhibition of nitric oxide synthase, we investigated the hypothesis
      that dietary salt intake determines the renal vascular response to L-arginine.
      Bolus intravenous doses of L-arginine given to anesthetized Sprague-Dawley rats
      caused dose-dependent increases in renal blood flow and decreases in renal
      vascular resistance, whereas D-arginine was not effective. The response to L
      arginine was prevented by pretreatment with NG-nitro-L-arginine methyl ester.
      Compared with rats adapted to a high salt diet, those adapted to a low salt diet
      were more sensitive to the reductions in blood pressure and renal vascular
      resistance (threshold dose of L-arginine for renal vascular resistance: low salt,
      2.9 +/- 0.9 mumol . kg-1 versus high salt, 20.0 +/- 6.2; P < .025), but the
      maximal changes in renal vascular resistance were similar (low salt, -43 +/- 5%
      versus high salt, -34 +/- 5%; P = NS). Bolus doses of L-glycine also caused dose
      dependent renal vasodilation, but the renal vasodilator responses were not
      affected by salt intake. Preinfusion of L-arginine augmented the renal
      vasoconstrictor response to NG-nitro-L-arginine methyl ester in low salt but not
      high salt rats; after L-arginine dietary salt no longer significantly affected
      the renal vasoconstrictor response to NG-nitro-L-arginine methyl ester. In
      conclusion, renal vasodilation is more sensitive to L-arginine during salt
      restriction. This effect is specific for L-arginine.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7635533
TI  - Cardiovascular and respiratory effects of endothelin in the ventrolateral medulla
      of the normotensive rat.
AB  - We studied the relevance of the ventrolateral medulla for the cardiovascular and
      respiratory effects of endothelin-1 in urethane-anesthetized rats. Microinjection
      of endothelin-1 into the rostral ventrolateral medulla (RVLM) evoked pressor and
      bradycardic effects followed by sustained decreases in blood pressure,
      bradycardia, and respiratory depression. These effects were inhibited by
      endothelin-A receptor antagonists (BQ-123 and BQ-610) but not by endothelin-B
      antagonists. In the caudal ventrolateral medulla (CVLM) endothelin-1 decreased
      blood pressure, renal sympathetic nerve activity, respiratory frequency, and
      phrenic nerve activity, whereas heart rate increased. Pretreatment with BQ-123 in
      the CVLM increased respiratory frequency by 15 +/- 6 breaths per minute and
      prevented the effects of intra-CVLM administration of endothelin-1. In separate
      experiments, the intracisternal administration of endothelin-1 (20 pmol) to rats
      pretreated with saline in both RVLM and CVLM resulted in a hypotensive and
      bradycardic phase that was followed by hypertension (50 +/- 15 mm Hg),
      bradycardia, and 100% mortality. In a separate group, pretreatment with BQ-123 in
      the RVLM and CVLM completely inhibited the hypotensive phase and reduced by 83%
      the subsequent rise in blood pressure evoked by endothelin-1. Cardiorespiratory
      arrest was prevented in all the rats in this group. Selective endothelin receptor
      blockade in the RVLM attenuated the hypertensive period of intracisternal
      administration of endothelin-1 and prevented mortality by 33%, whereas in the
      CVLM the endothelin receptor antagonist inhibited the initial hypotension and
      reduced mortality by 25%. Our results support the concept that in the ventral
      medulla, endothelin-1 can modulate cardiovascular and respiratory function.

PMID- 7635534
TI  - Effects of human renin in the vasculature of rats transgenic for human
      angiotensinogen.
AB  - Transgenic rats, which express the human angiotensinogen gene, provide a unique
      model for studying local vascular effects of human renin. We examined the
      cleavage of human angiotensinogen to angiotensin I (Ang I) by human renin and its
      inhibition by a human renin inhibitor in an isolated perfused hindlimb
      preparation from such rats. Perfusion resulted in the sustained release of human
      angiotensinogen, which decreased from 19.4 to 11.8 pmol/mL over 45 minutes.
      Active human renin at doses of 3, 10, and 30 ng/mL perfusate for 15 minutes
      increased Ang I release from undetectable levels (mean +/- SEM) to 31.9 +/- 3.3,
      147.1 +/- 26.2, and 206.4 +/- 17.1 fmol/mL, respectively, by 9 minutes. In
      separate experiments aimed at the quantification of renin-induced
      vasoconstriction, captopril decreased the perfusion pressure and lowered Ang II
      concentrations to nondetectable levels, whereas Ang I values increased sharply.
      When renin (30 ng/mL) was infused for 15 minutes, renin values in the perfusate
      decreased to barely detectable levels within minutes after termination of the
      infusion. However, Ang I values remained high for at least 30 minutes thereafter.
      The addition of a human renin inhibitor during renin infusion caused Ang I values
      to promptly decrease within minutes to undetectable levels. Hindlimbs from non
      transgenic control rats released no detectable amounts of Ang I, with or without
      human renin. Finally, by in situ hybridization we documented the presence of
      human angiotensinogen message in the vessels of the hindlimb. We conclude that
      renin acts on angiotensinogen at a site in the vascular wall. The cleavage
      depends on renin and not on other lysosomal proteases.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7635535
TI  - Altered angiotensinogen amino acid sequence and plasma angiotensin II levels in
      genetically hypertensive rats. A study on cause and effect.
AB  - The components of the renin-angiotensin system have been implicated in the
      development of primary hypertension in humans and genetically hypertensive rats.
      In humans a mutation in the angiotensinogen gene and elevated plasma
      angiotensinogen levels have been linked to primary hypertension. Although we had
      previously excluded a linkage of blood pressure to the angiotensinogen gene in
      the stroke-prone spontaneously hypertensive rat (SHRSP), elevated angiotensin II
      (Ang II) levels in this strain compared with the normotensive reference, the
      Wistar-Kyoto rat (WKY), prompted us to investigate further into the origins and
      effects of altered Ang II regulation using a range of physiological, biochemical,
      molecular, and genetic approaches. Ang II plasma levels determined by
      radioimmunoassay were confirmed to be significantly elevated in SHRSP compared
      with WKY. Sequence comparison among the two rat strains revealed a mutation in
      the coding region of the angiotensinogen gene that results in an isoleucine-to
      valine substitution in SHRSP at amino acid position 154 (I154V). We performed a
      cosegregation analysis in an F2 intercross cohort bred from SHRSP and WKY from
      the University of Heidelberg (SHRSPHD and WKYHD) to address the following
      questions: (1) whether this or another mutation of the angiotensinogen gene may
      be casually related to the observed differential Ang II plasma levels, (2)
      whether Ang II plasma levels may be correlated with blood pressure or organ
      hypertrophy, and (3) whether genetic linkage to the renin or angiotensin
      converting enzyme (ACE) gene loci (the two classic regulatory enzymes of the
      renin-angiotensin system) may provide an explanation for elevated Ang II plasma
      levels.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7635536
TI  - Gender and dietary NaCl in spontaneously hypertensive and Wistar-Kyoto rats.
AB  - We recently reported that high dietary NaCl exposure significantly increases both
      daytime and nighttime mean arterial pressure in male spontaneously hypertensive
      rats (SHR) but only nighttime values in male normotensive Wistar-Kyoto rats
      (WKY). In the present study we used a telemetry monitoring system to evaluate the
      effects of high dietary NaCl exposure on diurnal variation of mean arterial
      pressure and heart rate in male and female SHR and WKY. After implantation of a
      radio-frequency transducer, rats were fed either high (8%) or basal (1%) NaCl
      diets for 2 weeks. High dietary NaCl ingestion significantly increased both
      daytime and nighttime mean arterial pressure in male SHR compared with males
      receiving a basal NaCl diet, resulting in greater 24-hour values (163 +/- versus
      154 +/- 1 mm Hg, high versus basal NaCl diet; P < .05). High dietary NaCl
      ingestion significantly increased only nighttime blood pressure in male WKY, with
      no significant effect on 24-hour mean arterial pressure (102 +/- 2 versus 101 +/-
      3 mm Hg, high versus basal). High dietary NaCl exposure did not affect daytime or
      nighttime mean arterial pressure in female SHR (24-hour mean arterial pressure,
      144 +/- 2 versus 141 +/- 2 mm Hg, high versus basal NaCl diet). Twenty-four-hour
      mean arterial pressure tended to be lower in female WKY receiving a high NaCl
      diet than females ingesting a basal diet (101 +/- 3 versus 106 +/- 1 mm Hg), but
      the difference was not significant.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7635537
TI  - Insulin modulation of vascular reactivity is already impaired in prehypertensive
      spontaneously hypertensive rats.
AB  - Hyperinsulinemia reduces the vasoconstrictive response to norepinephrine in
      Wistar-Kyoto rats (WKY) but not in spontaneously hypertensive rats (SHR). It has
      been hypothesized that this difference in the vascular effect of insulin could be
      a hallmark of the hypertensive state. To test this hypothesis we studied SHR
      before (5 weeks old, n = 10) and after (15 weeks old, n = 10) the establishment
      of hypertension as well as two groups of age- and sex-matched WKY (5 weeks old, n
      = 14; 15 weeks old, n = 13). Blood pressure was significantly higher in SHR
      compared with WKY (181 +/- 5 versus 118 +/- 6 mm Hg, respectively, P < .001) in
      the 15-week-old rats but not in the 5-week-old rats (121 +/- 5 versus 117 +/- 3
      mm Hg, P < NS). We tested vascular reactivity using increasing amounts of
      norepinephrine (from 10(-10) to 10(-5) mmol/L) on isolated aortic rings in
      control conditions and after 30 minutes of exposure to 715 pmol/L insulin. In WKY
      insulin reduced the vascular response to norepinephrine in both the 5-week-old
      (repeated-measures ANOVA with grouping factor: F = 2.443, P < .05) and 15-week
      old (F = 9.667, P < .01) groups. In SHR at both ages insulin failed to modify the
      vascular response to norepinephrine (5 weeks: F = 0.107, P < NS; 15 weeks: F =
      0.075, P < NS). Sodium nitroprusside was able to attenuate the vascular response
      to norepinephrine in WKY and SHR at 5 and 15 weeks.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7635538
TI  - Regional hemodynamic and endocrine effects of aldosterone and cortisol in
      conscious sheep. Comparison with the effects of corticotropin.
AB  - We studied the cardiovascular responses to 5 days' infusion of aldosterone (10
      micrograms/h) and cortisol (5 mg/h) to determine the possible contribution of
      mineralocorticoid and glucocorticoid actions to the regional hemodynamic changes
      caused by corticotropin. These infusion rates produce plasma levels similar to
      those seen during corticotropin stimulation. In five conscious sheep aldosterone
      progressively increased mean arterial pressure (P < .001) to a maximum of 11 mm
      Hg on day 5, whereas cortisol increased pressure by 5 mm Hg (P < .01) within 24
      hours. Cardiac outputs on the control day and on day 5 of infusion were 4.4 +/-
      0.3 and 4.9 +/- 0.3 L/min, respectively, for aldosterone and 4.3 +/- 0.4 and 5.0
      +/- 0.4 L/min for cortisol. Neither steroid significantly altered total
      peripheral conductance, but they had different, nonuniform regional hemodynamic
      effects. Mesenteric conductance fell progressively with aldosterone from 7.14 +/-
      0.35 (mL/min)/mm Hg to a minimum of 6.17 +/- 0.38 (P < .01) on day 5 of infusion.
      Mesenteric conductance was transiently reduced with cortisol, but this was not
      significant over the 5 days. Renal conductance was unchanged with aldosterone,
      but cortisol caused a rapid, sustained increase in renal conductance from 2.9 +/-
      0.3 to 4.0 +/- 0.4 (mL/min) / mm Hg (P < .001) within 24 hours, similar to the
      increase caused by corticotropin. As with corticotropin there were only minor
      changes in the coronary and iliac vascular beds. In summary, these two endogenous
      steroids had contrasting, nonuniform regional hemodynamic effects, aldosterone
      causing mesenteric vasoconstriction, and cortisol causing renal
      vasodilatation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7635539
TI  - Pulse pressure and resistance artery structure in the elderly.
AB  - There has been recent interest in the possibility that resistance vessel
      structural adaptation in hypertension may be more closely related to pulse
      pressure than to other blood pressure parameters. We investigated the relation
      between blood pressure and resistance vessel structure in a group of subjects
      from an age group (older than 60 years) in which a widening of pulse pressure is
      a typical finding and characterized blood pressure parameters using 24-hour
      ambulatory blood pressure monitoring. We studied resistance vessels retrieved
      from biopsies of skin and subcutaneous fat taken from the gluteal region of 32
      subjects under local anesthesia (age, 70 +/- 1 years [mean +/- SEM], 21 of whom
      were hypertensive and 11 normotensive. Media-lumen ratio was higher in the
      hypertensive than the normotensive subjects (18.6 +/- 1.6% versus 12.8 +/- 1.2%,
      P < .01) and correlated with age (r = .44, P < .05), clinic systolic pressure (r
      = .35, P < .05), 24-hour systolic pressure (r = .40, P < .05), and 24-hour pulse
      pressure (r = .56, P < .001). Stepwise multivariate regression analysis
      identified clinic and 24-hour pulse pressure as the only significant predictors
      of media-lumen ratio independent of age, other parameters of clinic blood
      pressure, and blood pressure variability (R2 = 41%, P < .05). These findings
      confirm those from animal models of hypertension in demonstrating the importance
      of pulse pressure in relation to cardiovascular structural adaptation and have
      important implications for the goals of treatment of hypertension in the elderly.

PMID- 7635540
TI  - Physiological influences on continuous finger and simultaneous intra-arterial
      blood pressure.
AB  - Because of the clinical and experimental utility of continuous finger blood
      pressure measurements and the need for accuracy, we tested the performance of a
      new hydraulic device in 22 consecutive hypertensive subjects during physiological
      and pharmacological interventions. Ipsilateral brachial intra-arterial pressure
      was monitored during rest, Valsalva's maneuver, static handgrip, and mental
      arithmetic and after sublingual glyceryl trinitrate. In excess of 40,000 blood
      pressure values were analyzed. Average bias (intra-arterial minus finger blood
      pressure) was 8.2 +/- 17.0 mm Hg (mean +/- SD, P = NS) for systolic and 2.8 +/-
      10.4 mm Hg (P = NS) for diastolic pressure. Two-way ANOVA of biases with subject
      and task factors showed a subject effect (P < .001). Intersubject and
      intrasubject standard deviations of bias were 13.8 and 9.8 mm Hg systolic and 8.7
      and 5.7 diastolic, respectively. Linear drift (millimeters of mercury per minute)
      of finger pressure was greater (P < .001) for systolic than diastolic pressure
      during static exercise and math and after glyceryl trinitrate. Coefficients of
      determination for blood pressure ranged from 0.4 +/- 0.3 to 0.8 +/- 0.3 during
      the tasks. We conclude that (1) noninvasive finger blood pressure faithfully
      follows intra-arterial changes but with clinically relevant offsets, (2) this
      technique is best suited for assessing pressure changes, (3) physiological and
      pharmacological interventions do not consistently affect finger pressure
      accuracy, (4) many reports of finger blood pressure measuring devices are based
      on direct readings obtained with inadequate system response characteristics, and
      (5) the tested instrument falls short of the standard requirements (bias < or = 5
      +/- 8 mm Hg) for devices that measure intermittently.

PMID- 7635541
TI  - Effect of regional and systemic changes in vasomotor tone on finger pressure
      amplification.
AB  - Pulse wave amplification, which leads to increased peripheral systolic pressure,
      is observed during vasoconstriction after head-up tilt and during exercise. This
      may influence finger pressure measurements with the Finapres. To distinguish
      between changes in regional vascular tone and changes in systemic hemodynamics as
      a cause of pulse wave amplification, we measured finger pressure, intra-arterial
      brachial artery pressure, heart rate, and left ventricular ejection time during
      high-dose intravenous and low-dose intra-arterial infusions of phenylephrine and
      sodium nitroprusside in eight subjects. Forearm blood flow was measured by means
      of venous occlusion plethysmography. Intravenous phenylephrine at the highest
      dose caused an increase in mean brachial artery pressure of 24 +/- 3 mm Hg, a
      decrease in heart rate of 10 +/- 11 beats per minute, and an increase in ejection
      time of 23 +/- 9 milliseconds (all P < .01), whereas pulse wave amplification was
      reduced. Finapres underestimated the rise in systolic brachial artery pressure of
      41 +/- 9 mm Hg by 11 +/- 12 mm Hg (P < .01). Forearm blood flow did not change.
      Intravenous nitroprusside caused a decrease in mean brachial artery pressure of
      23 +/- 9 mm Hg, an increase in heart rate of 18 +/- 11 beats per minute, and a
      decrease in ejection time of 36 +/- 31 milliseconds (all P < .01), whereas pulse
      wave amplification increased. Finapres underestimated the fall in systolic
      brachial artery pressure of 30 +/- 13 mm Hg by 9 +/- 10 mm Hg (P < .05). Forearm
      blood flow did not change. During regional infusion of phenylephrine and
      nitroprusside forearm flow halved and doubled, respectively.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7635542
TI  - Contribution of systemic blood pressure to myocardial remodeling in uremic rats.
AB  - Left ventricular hypertrophy with diffuse intermyocardiocytic fibrosis is a
      feature of uremia. The role of blood pressure and/or other cardiovascular uremic
      risk factors in cardiac remodeling is still uncertain. To determine the extent to
      which improvement of kidney function and the control of uremia-related risk
      factors are associated with a reduction of myocardial injury, we evaluated the
      effect of dietary protein restriction or the angiotensin-converting enzyme
      inhibitor lisinopril on cardiac structure in remnant kidney rats. One week after
      subtotal nephrectomy, Wistar rats were allocated to receive drinking water
      solution (group 1), 5 mg/kg per day lisinopril (group 2), or a low-protein diet
      (6%) (group 3) for 12 weeks. Group 2 and 3 showed a comparable efficacy in
      preventing the expected rise in creatininemia, urinary protein excretion, and
      glomerulosclerosis. However, hypertension development was prevented only in group
      2. Groups 1 and 3 developed a significant (P < .01) increase in left ventricular
      weight (2.45 +/- 0.1 and 2.5 +/- 0.5 mg/g body wt, respectively) compared with
      group 2 (1.9 +/- 0.06 mg/g body wt). Cardiac hydroxyporline concentration was
      also lower in group 2 compared with group 1 (2.07 +/- 0.16 versus 2.73 +/- 0.17
      mg/g left ventricular weight, P < .05) but not compared with group 3 (2.59 +/-
      0.19 mg/g left ventricular weight). The effect of angiotensin-converting enzyme
      inhibition on left ventricular mass and intracardiac collagen content appeared to
      be dissociated from anemia, sympathetic activity, and hyperlipidemia. There was a
      close relationship between systolic pressure and left ventricular mass; however,
      no relationship between the degree of cardiac fibrosis and systolic pressure
      could be determined.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7635543
TI  - Role of basal and stimulated release of nitric oxide in the regulation of radial
      artery caliber in humans.
AB  - Although it is well established that nitric oxide contributes to the regulation
      of resistance arterial tone in humans, its role at the level of large arteries is
      less clear. Therefore, we assessed in healthy volunteers the effect of local
      administration of the inhibitor of nitric oxide synthesis NG-monomethyl-L
      arginine (L-NMMA) on basal radial artery diameter (transcutaneous A-mode
      echotracking) and radial blood flow (Doppler) as well as on the radial response
      to acetylcholine and the nitric oxide donor sodium nitroprusside. A catheter was
      inserted into the brachial artery for measurement of arterial pressure and
      infusion of L-NMMA (2, 4 and 8 mumol/min for 5 minutes, n = 11), acetylcholine
      (3, 30, 300 and 900 nmol/min for 3 minutes, n = 8), and nitroprusside (2.5, 5,
      10, and 20 nmol/min for 3 minutes, n = 6). None of the treatments affected
      arterial blood pressure or heart rate. L-NMMA dose-dependently decreased radial
      blood flow (from 31 +/- 6 to 17 +/- 3 10(-3) L/min after 8 mumol/min, P < .01)
      but did not affect radial artery diameter (from 2.93 +/- 0.11 to 2.90 +/- 0.14
      mm). Acetylcholine dose-dependently increased radial blood flow (154 +/- 43%
      after 900 nmol/min) and radial artery diameter (16 +/- 4%), and both effects were
      markedly reduced after L-NMMA (increase in radial blood flow and radial artery
      diameter: 22 +/- 20% and 3 +/- 2%, respectively; both P < .01 versus controls).
      Nitroprusside also dose-dependently increased radial artery diameter (14 +/- 4%
      after 20 nmol/min) but only moderately affected radial blood flow (47 +/-
      21%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7635544
TI  - Aortic distensibility and structural changes in sinoaortic-denervated rats.
AB  - The purpose of the present study was to determine the effects of chronic
      sinoaortic denervation on the mechanical properties and composition of the
      abdominal aorta in Wistar rats. We used a high-resolution echotracking system to
      determine in situ under physiological conditions of blood flow and arterial wall
      innervation the aortic diameter-, compliance-, and distensibility-pressure curves
      in 16-week-old anesthetized rats that had been denervated at 10 weeks of age for
      6 weeks (n = 8). Compared with sham-operated rats (n = 8) we observed a marked
      reduction of baroreflex response and increase in overall mean blood pressure
      variability as measured by standard deviation and spectral analysis in sinoaortic
      denervated rats. Mean blood pressure was not affected by sinoaortic denervation
      in both conscious and anesthetized rats. Sinoaortic denervation significantly
      shifted the distensibility-pressure curve toward lower levels of distensibility,
      indicating a decreased aortic distensibility for a given level of arterial
      pressure. Sinoaortic denervation produced a significant increase of aortic wall
      cross-sectional area and collagen content, one of the less-distensible components
      of the arterial wall. These results suggest that intact arterial baroreceptors
      are necessary for maintaining normal functional and structural properties of
      large arteries in rats. The reduction in arterial distensibility in chronic
      sinoaortic-denervated rats may have resulted from different factors, including
      the initial hypertensive phase, aortic wall hypertrophy, and increase in collagen
      content. The changes in aortic wall structure and related reduction in aortic
      distensibility, in addition to other mechanisms, might have been direct
      consequences of an increased blood pressure variability.

PMID- 7635547
TI  - Aortic wall properties in normotensive and hypertensive rats of various ages in
      vivo.
AB  - The distensibility of the arterial system, which is partly determined by arterial
      wall structure, smooth muscle tone, and actual pressure level, decreases with
      aging and hypertension. Our aim was to compare aortic wall properties in 3- and 6
      month-old normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive
      rats (SHR) at comparable blood pressures in vivo. During ketamine/xylazine
      anesthesia in rats we performed ultrasound arterial wall tracking and invasive
      pressure measurements to determine, at the level of the thoracic aorta, diastolic
      pressure, diastolic lumen area, changes in pressure and lumen area during the
      cardiac cycle, and indexes of compliance and distensibility. These observations
      were combined with histological measurements for determination of media cross
      sectional area and thickness and the incremental elastic modulus under conditions
      as expected in situ. Anesthesia abolished the difference in diastolic pressure
      between SHR and WKY. Between 3 and 6 months of age in WKY, diastolic area and
      incremental elastic modulus increased significantly, distensibility decreased,
      and all other recorded variables were not modified. Between 3 and 6 months of age
      in SHR, diastolic area and incremental elastic modulus increased, distensibility
      of the aortic wall decreased, and all other mechanical and structural properties
      did not change significantly. At both ages, diastolic area and compliance were
      significantly smaller in SHR than WKY. The other mechanical and structural
      properties measured or calculated at comparable pressure did not differ between
      strains. Differences between the aorta of 3- and 6-month-old rats and between
      strains observed in vivo at comparable pressures can largely be attributed to
      differences in lumen caliber.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7635546
TI  - Arterial wall hypertrophy and stiffness in essential hypertensive patients.
AB  - The purpose of this article is to review some clinical and fundamental evidence
      that hypertension-induced arterial wall hypertrophy at the site of large and
      medium-sized arteries is not necessarily associated with a decreased arterial
      distensibility and increased elastic modulus, and to demonstrate the opposing
      effects of aging and hypertension-induced hypertrophy on the arterial mechanics
      in vivo. in the studies reported here, the elastic properties of large and medium
      sized arteries were noninvasively assessed from the simultaneous measurement of
      internal diameter and blood pressure inside the systolic-diastolic range. The
      distensibility of a medium-sized artery, the radial artery, in untreated
      essential hypertensive patients was not significantly different from that of
      normotensive control subjects when the two groups were compared at their
      respective mean arterial pressures. Despite increased wall thickness, the
      stiffness of the radial artery wall material, assessed by the incremental modulus
      of elasticity (Young's modulus), was not increased in hypertensive patients. At
      the site of a larger, more elastic artery, such as the common carotid artery,
      distensibility of hypertensive patients was significantly lower than that of
      normotensive subjects when the two groups were compared at their respective mean
      arterial pressures, but distensibility at 100 mm Hg was not significantly
      different between the two groups. Aging may alter distensibility independently of
      blood pressure, because carotid distensibility at 100 mm Hg was negatively
      correlated with age. In spontaneously hypertensive rats the elastic modulus of
      the common carotid artery wall material was not significantly different from that
      of Wistar-Kyoto rats at a given circumferential stress.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7635545
TI  - Sympathetic modulation of radial artery compliance in congestive heart failure.
AB  - Animal studies have suggested that arterial compliance can be modulated by
      adrenergic influences. Whether this adrenergic modulation also occurs in humans
      is still a matter of debate. In the present article we address this issue by
      examining the relationships between sympathetic tone and arterial compliance in a
      variety of physiological and pathophysiological conditions. We have found that
      cigarette smoking, ie, an action that produces a marked sympathetic activation,
      causes a significant reduction in radial artery compliance, as measured by an
      echotracking device capable of providing continuous beat-to-beat evaluation of
      this hemodynamic variable. When expressed as compliance index, ie, as the ratio
      between the area under the compliance-pressure curve and pulse pressure, the
      reduction amounted to 35.7 +/- 4.8% (mean +/- SEM) and was independent of the
      smoking-related blood pressure increase. Furthermore, pharmacological stimulation
      of adrenergic receptors located in the arterial wall was also shown to affect
      arterial compliance because the radial artery compliance index was markedly
      reduced (- 29.5 +/- 3.9%) during phenylephrine infusion in the brachial artery at
      doses devoid of any systemic blood pressure effect. Evidence was also obtained
      that the relationship between sympathetic activation and arterial compliance has
      pathophysiological relevance, because in 17 patients with congestive heart
      failure (New York Heart Association classes II through IV) there was a
      significant inverse correlation (r = .62, P < .01) between muscle sympathetic
      nerve activity (directly measured by microneurography in the peroneal nerve) and
      radial artery compliance.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7635548
TI  - Prevalence and determinants of cardiac and vascular hypertrophy in hypertension.
AB  - Hypertrophy of the capacitance arteries has recently been documented in
      hypertensive patients by noninvasive ultrasound techniques. To better define the
      prevalence and determinants of vascular hypertrophy and its potential association
      with ventricular hypertrophy in hypertension, we compared carotid and cardiac
      ultrasound findings in 172 normotensive and 172 unmedicated hypertensive subjects
      matched for age and sex. Despite similar body size, hypertension was associated
      with increased left ventricular wall thicknesses, mass, and mass index (89 versus
      80 g/m2, P < .0001 for all comparisons) and increased carotid wall thickness
      (0.82 versus 0.77 mm) and cross-section area (17.1 versus 15.3 mm2, P < .005 for
      both comparisons). Among the 172 normotensive subjects, left ventricular
      hypertrophy was noted in 9 (5.2%) and arterial hypertrophy was found in 9 (5.2%),
      whereas ventricular hypertrophy was found in 21 (12.2%) and arterial hypertrophy
      in 19 (11%) hypertensive subjects. Arterial hypertrophy was found in 9% of
      hypertensive subjects with normal ventricular mass and in 24% with left
      ventricular hypertrophy (P < .05). Among hypertensive subjects carotid wall
      thickness and cross-sectional area were most strongly related to age and systolic
      pressure (P < .0001 for all comparisons), with little contribution form body
      size. Carotid relative wall thickness was only related to increasing age (P <
      .01). In contrast, left ventricular wall thickness and mass were strongly related
      to body size and systolic pressure (P < .0001 for comparisons) but not to age (P
      = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7635549
TI  - Cell volume and blood pressure.

PMID- 7635550
TI  - Does blockade of the renin-angiotensin system prevent heritability of genetic
      hypertension?

PMID- 7635552
TI  - Perfluorocarbon emulsions: one approach to intravenous artificial respiratory gas
      transport.
AB  - The PFC emulsions have had a developmental history of promise as yet unfulfilled.
      Today, second-generation PFC emulsions are poised with the right gas-carrying
      capabilities to be able to make significant contributions to oxygen transport and
      delivery. The dream of stable, safe, easily transportable intravenous fluid, with
      universal rapid application is not yet at hand. However, we appear to be a great
      deal closer than in the mid 1980s. If these 40% volume-to-volume emulsions prove
      safe, then an entirely new realm of therapeutic options will become available.
      Not only will the uses for trauma and acute blood loss replacement become a
      reality, but extremes of euvolemic hemodilution may become possible. The use of
      these compounds for prevention of stroke, ischemic organ salvage, and prevention
      of air embolism or decompression sickness are particularly exciting. It is clear
      from the recent developments in PFC technology that some product will come to
      market in the not-too-distant future. How such a PFC will be utilized as compared
      with hemoglobin preparations is yet to be discerned, but the two concepts are
      quite different. Each will have its own specific indications.

PMID- 7635551
TI  - New antiemetic drugs.
AB  - In an editorial, Kapur [4] described perioperative nausea and vomiting as the big
      "little problem following ambulatory surgery." In contrast to the attitudes of
      some physicians, patients put a high value on freedom from nausea and emesis in
      the postoperative period and are willing to accept some pain and drowsiness as
      the cost of controlling PONV [85]. Until recently, there had been little change
      in the incidence of postoperative emesis since the introduction of halothane into
      clinical practice in 1956. However, the introduction of the IV anesthetic agent
      propofol and of the NSAID ketorolac, plus abandonment of the policy of insisting
      that patients drink before discharge, appear to have contributed to a recent
      decline in the incidence of emesis. With the availability of new antiserotonin
      drugs, the incidence of recurrent (intractable) emesis could be further
      decreased, particularly if combination therapy is used. Further research into the
      mechanisms of this common postoperative complication may help in improving the
      management of emetic sequelae in the future. Improvements in antiemetic therapy
      could have a major impact for surgical patients, particularly those undergoing
      ambulatory surgery. Just as pain is no longer considered an unavoidable part of
      the postoperative experience, so should nausea and vomiting be considered an
      avoidable side effect.

PMID- 7635553
TI  - The development of hemoglobin solutions as red cell substitutes.
AB  - It is clear from the trials described here that the number of different products
      being tested and the potential variation between batches of the same product
      present major problems in evaluating the safety and efficacy of hemoglobin-based
      oxygen carriers. The recent CBER "Points to Consider" document [42] makes clear
      that an understanding of the safety of oxygen carriers in humans is of paramount
      importance. In the event of phase II or indeed phase III trials being approved,
      the need may still remain for additional phase I or preclinical studies,
      particularly as unwanted or toxic properties of the solutions affect efficacy. It
      is likely that demonstrating safety and efficacy in acute hemorrhagic shock will
      be the most difficult task, as this is a complex clinical indication and is often
      accompanied by multisystem damage. The use of a hemoglobin-based oxygen carrier
      in this setting must have a distinct advantage over a plasma expander alone. In
      the application of perioperative transfusion, a decreased requirement for red
      cell transfusion has already been accepted as a basis for the efficacy for
      erythropoietin. However, in the case of a hemoglobin-based oxygen carrier, the
      reduction of red cell requirement in perioperative procedures would need to be
      balanced against any adverse drug reactions or unacceptable hemodynamic effects
      that may be caused by the product. It appears that there are still numerous
      hurdles to overcome in the development of hemoglobin-based red cell substitutes.
      Before these products can become established in medical practice, it is
      imperative that the potential mechanisms of toxicity of cell-free hemoglobin are
      clearly understood. Approval of hemoglobin-based oxygen carriers for clinical use
      will depend not only on clear demonstration of both safety and efficacy but also
      on risk-versus-benefit issues. Our understanding of the physiological effects of
      these products will evolve as progress is made in their clinical evaluation.

PMID- 7635554
TI  - Propofol: a new drug for sedation in the intensive care unit.
AB  - Patients in the ICU who require intubation and mechanical ventilation benefit
      from adequate sedation and analgesia. Traditionally, this has been achieved using
      benzodiazepines and opioids. Alternatively, propofol is being administered for
      sedation of patients in the ICU with increasing frequency. Propofol has a number
      of properties that make it a potentially superior choice for sedation of
      intubated ICU patients. The rapid onset and offset of sedation with propofol,
      even after prolonged administration, allow for greater control over the level of
      sedation and more rapid weaning from mechanical ventilation. In addition, long
      term administration of propofol does not appear to be associated with the
      development of tolerance, addiction, or withdrawal following discontinuation.
      Propofol suppresses cellular oxygen consumption and carbon dioxide production
      without increasing anaerobic metabolism. This may be beneficial in patients with
      severe hypoxemia, hypercarbia, or myocardial ischemia. Finally, the use of
      propofol may reduce or eliminate the need for other medications in these patients
      such as muscle relaxants, antihypertensives, lipid nutritional supplements, and
      analgesics, thereby simplifying their medication regimens and reducing the
      overall cost of their care while in the ICU. Propofol can be administered to
      critically ill patients for sedation with a high degree of safety and efficacy.
      Propofol causes systemic vasodilatation which may result in unwanted hypotension,
      especially in patients who are already hemodynamically compromised. Propofol also
      causes ventilatory depression, so its use should be restricted in the ICU to
      patients whose airway is protected by an endotracheal tube and whose ventilation
      is closely monitored. Finally, continuous administration of propofol may cause
      clinically significant hypertriglyceridemia in patients with disordered
      triglyceride metabolism, or in patients receiving excessive doses of propofol or
      parenteral lipid supplements. Although propofol is more expensive than equipotent
      doses of other sedative agents, the additional cost of using propofol for
      sedation of critically ill patients in the ICU may be more than offset by the
      savings accrued from faster times to extubation, shorter ICU stays, and the use
      of fewer medications to manage these patients. Further research needs to be done
      to determine the potential clinical and cost benefits of using propofol for
      sedation of patients in the ICU.

PMID- 7635556
TI  - New cardiac drugs.
AB  - The positive inotropic agents, including beta-adrenergic receptor agonists and
      PDE III inhibitors, are reviewed to explain their mechanisms of action,
      pharmacology, and clinical usage. New cardiotonic drugs, such as dopexamine and
      dobutamine (beta-adrenergic receptor agonists) and amrinone, milrinone, and
      enoximone (PDE III inhibitors), have important roles for the treatment of
      perioperative acute heart failure or acute deterioration of congestive heart
      failure. PDE III inhibitors have important roles as effective inodilator agents,
      and understanding their actions, pharmacology, and appropriate usage is
      important. Nicardipine, the first dihydropyridine calcium-channel blocker
      available for intravenous use, represents an arterial-specific vasodilator that
      offers an important therapeutic approach to treat perioperative hypertension.

PMID- 7635555
TI  - Inhaled nitric oxide in anesthesia and critical care medicine.
AB  - Inhaled NO is an exciting new drug and has enormous potential in the therapy of a
      wide variety of acute, and possibly chronic, cardiopulmonary disorders. No
      reports of controlled, randomized, and blinded trials have been published
      concerning the use of inhaled NO in any clinical condition. In the United States,
      use of inhaled NO currently requires an investigational new drug approval from
      the Food and Drug Administration. Physicians involved in anesthesia and critical
      care medicine have a unique opportunity to validate a new mode of therapy in
      acute care, and optimal evaluation should be undertaken so that the real
      therapeutic role of inhaled NO may be defined.

PMID- 7635557
TI  - New skeletal muscle relaxants.
AB  - In a little over 10 years, six new muscle relaxants have been introduced in
      clinical practice. The first two, intermediate-duration vecuronium and
      atracurium, were outstanding drugs and clearly an advance over the earlier,
      longer-acting drugs. With their introduction, the phenomenon of "recurarization"
      largely disappeared. The next two, long-acting doxacurium and pipecuronium, were
      relics of an earlier era and have made little clinical impact. Mivacurium created
      a new class, the short-acting nondepolarizing relaxant, and caused
      succinylcholine to be reclassified as an ultra-short-acting drug. However,
      mivacurium has neither the rapid onset nor the ultra-short duration of
      succinylcholine. Rocuronium is the first nondepolarizing relaxant with an onset
      approaching that of succinylcholine. It is likely that we will see the
      introduction of at least two more drugs, Org 9487 and 51W89, by the end of this
      decade, and the goal of developing a nondepolarizing relaxant that is a complete
      replacement for succinylcholine may not be too far in the future.

PMID- 7635558
TI  - New drugs in anesthesia.
AB  - The lower solubilities of desflurane and sevoflurane provide a clear advantage
      over older potent agents, permitting more precise control over the delivery of
      anesthesia and more rapid recovery from anesthesia. Other pharmacological
      properties of these two agents at concentrations of 1 MAC or less differ little
      from those of older agents. Sevoflurane differs from desflurane in that it is
      without pungency and useful for induction of anesthesia by inhalation. It is less
      prone to increase pulse rate at higher concentrations. Desflurane also can cause
      transient increases in pulse rate and blood pressures when its concentration is
      rapidly increased above 6%. Sevoflurane has the disadvantage of vulnerability to
      degradation in vitro and in vivo, raising a concern regarding a subtle toxicity.
      Although neither of these new anesthetics can be said to be ideal, each may be a
      step in that direction.

PMID- 7635559
TI  - Alpha 2-adrenoceptor agonists and anesthesia.

PMID- 7635560
TI  - Risk of cutaneous melanoma associated with pigmentation characteristics and
      freckling: systematic overview of 10 case-control studies. The International
      Melanoma Analysis Group (IMAGE).
AB  - Using individual subject data from 10 case-control studies, comprising over 3000
      cases and almost 4000 controls, we have estimated the relative risk of melanoma
      associated with aspects of complexion, namely, hair, eye and skin colour and
      freckling in adulthood, and have examined the relationships between these factors
      and naevus count in terms of melanoma risk. Compared with individuals with black
      or dark brown hair, the relative risks for developing melanoma in those with
      light brown, blonde and red hair were 1.49 (95% CI 1.31, 1.70), 1.84 (95% CI
      1.54, 2.21) and 2.38 (95% CI 1.90, 2.97), respectively. Individuals with blue
      eyes had a risk 1.55 (95% CI 1.35, 1.78) times that for those with brown eyes, or
      1.15 (95% CI 0.94, 1.40) after adjusting for hair colour and freckling in
      adulthood. The relative risks associated with hair and eye colour were
      independent of those for naevus count and skin colour. Light skin colour and high
      freckle density were also highly significant risk factors, independent of each
      other and of naevus count and hair and eye colour. The risks associated with
      these factors, while individually modest, are largely independent, and thus
      pigmentation characteristics and freckling tendency should be useful in
      identifying high risk groups to be targeted for prevention.

PMID- 7635561
TI  - Risk of cutaneous melanoma associated with a family history of the disease. The
      International Melanoma Analysis Group (IMAGE).
AB  - In a combined analysis of 2952 melanoma patients and 3618 controls from 8 case
      control studies in white populations the risk of cutaneous melanoma was 2.24-fold
      higher (95% CI, 1.76-2.86) in subjects who reported at least one affected first
      degree relative than in subjects who did not. There was no evidence for
      heterogeneity in the relative risk between the studies, which were from a wide
      range of latitudes and hence degrees of sun exposure. The effect of family
      history on melanoma risk was independent of age, naevus count, hair and eye
      colour, and freckling. There was no evidence for a relationship between family
      history and primary site of melanoma but there was some suggestion that the
      familial patients were more likely to have superficial spreading melanoma or
      lentigo maligna melanoma than acral lentiginous melanoma or nodular melanoma.

PMID- 7635562
TI  - Inflammatory carcinomas of the breast: a clinical, pathological, or a clinical
      and pathological definition?
AB  - Some controversy remains about the clinical or pathological definition of the
      different types of inflammatory breast cancer (IBC) and especially the diagnostic
      and prognostic value of dermal lymphatic involvement. Our purpose was to classify
      the different types of IBC for which diagnosis was confirmed intraoperatively and
      ascertain features allowing reliable diagnosis. We studied clinical findings,
      biological data, and treatment outcome in a series of 144 successive patients.
      Our results suggest that there are 2 biologically different entities i.e., true
      IBC and pseudo-IBC. True IBC, whose course is currently fatal in all cases, can
      be divided into 2 sub-categories i.e., common true IBC (75.7% of cases), in which
      inflammatory signs occur primarily or secondarily, and occult true IBC (13.2% of
      cases). Dermal emboli have been observed in 61% of common true IBC, but their
      absence did not alter the rapidly unfavourable outcome. Extensive lymph-node
      involvement, other biological features and survival were the same in the 2 sub
      categories. Pseudo-IBC (11.1% of cases) can easily be confused with common true
      IBC. The biological characteristics of pseudo-IBC differ from those of true IBC:
      no dermal lymphatic involvement and little or no lymph-node involvement. Despite
      large tumour size, outcome was particularly favourable. It is of great importance
      to differentiate true and pseudo-IBC, for which the treatments are different.
      Confirmation of true IBC requires pathological demonstration of dermal lymphatic
      emboli or extensive lymph-node involvement. Occult IBC must be identified for
      patients presenting rapidly growing tumours.

PMID- 7635563
TI  - Enhanced expression of transforming growth factor-beta and its type-I and type-II
      receptors in human glioblastoma.
AB  - Immunohistochemical studies of transforming growth factor-beta (TGF-beta) and its
      receptors have been carried out on 16 glioma tissues and compared with 5 cases of
      gliosis. Significantly higher expressions of TGF-beta I, as well as type-I and
      type-II TGF-beta receptors (T beta R-I and T beta R-II, respectively), were
      observed in advanced-malignant-glioma tissues when compared with non-tumorous
      gliosis. Immunoreactivities of TGF-beta and T beta R-I were localized in the
      cytoplasm of spindle-shaped tumor cells surrounding proliferating vessels or
      around areas of necrosis. The advancing edge of the tumor clusters frequently
      stained positive. Similar expression patterns were found for TGF-beta 2 and TGF
      beta 3, whereas only weak or no expression was found for endoglin. In low-grade
      astrocytomas and in gliosis cases, the expression was moderate for T beta R-I and
      weak for TGF-beta and T beta R-II. In 3 examined human malignant glioma cell
      lines, clear immunostainings were detected for TGF-beta and its receptors. Ligand
      induced heteromeric complexes of the receptors were formed in these cell lines,
      but the amount of the receptors was less than that of mink lung epithelial cells,
      which are sensitive target cells for TGF-beta. TGF-beta I showed no growth
      inhibitory activity on any of these glioma cell lines. These results suggest that
      malignant gliomas produce TGF-beta and receptors, but are refractory to TGF-beta,
      implying dysregulation in the signalling pathway in the tumor cells. It is
      possible that the released TGF-beta acts on neighboring cells and affects stromal
      growth, angiogenesis, metastasis or immune surveillance in human glioma.

PMID- 7635564
TI  - Overall and site-specific risk of malignant melanoma associated with nevus counts
      at different body sites: a multicenter case-control study of the German Central
      Malignant-Melanoma Registry.
AB  - A large number of benign melanocytic nevi is the major risk factor for malignant
      melanoma (MM). In a multicenter case-control study, the number of common (CN) and
      clinically atypical (AN) nevi were counted separately at individual sites in 278
      melanoma patients and 278 age- and gender-matched non-melanoma controls. Relative
      risk (RR) adjusted for age and sex was calculated. In men as well as women, the
      number of CN on the legs was the best predictor of overall melanoma risk. In men,
      RR for developing MM when > or = 1 AN were present on the trunk was 4-fold (vs.
      none). In women, presence of AN on the arms increased RR 9.5-fold. For men and
      women combined, after adjusting for age and gender, the RR for developing MM on
      the trunk and on the legs was best predicted by counts of CN at the respective
      body region. However, high counts of CN on the arms were associated with high
      melanoma risk on the legs (somewhat lower on the trunk). For AN, no site
      specificity of melanoma risk was found. Our data suggest that nevus counts of the
      legs are the best predictor of overall melanoma risk if total body nevus counts
      are not feasible. Although high counts of CN on the trunk and legs are associated
      with a higher risk of developing MM at the respective site than at another site,
      our data do not unequivocally support a direct site-specific melanoma risk.

PMID- 7635565
TI  - Translocation t(9;22)(q22;q12) is a primary cytogenetic abnormality in
      extraskeletal myxoid chondrosarcoma.
AB  - The cytogenetic and in vitro growth characteristics of 3 cases of extraskeletal
      myxoid chondrosarcoma (EMC) are described. In cell culture, the tumor cells
      retained the immunocytochemical and ultrastructural characteristics of EMC.
      Cytogenetically, 2 of the cases showed an apparently identical t(9;22)(q22;q12).
      In one case, the t(9;22) was found together with a dup(I)(q12q44), and in the
      other case it was found together with several other aberrations. The third case
      had an inv(10)(p11.2q22) as the sole karyotypic abnormality. Of 4 cases of EMC
      previously analyzed, 2 showed a t(9;22)(q22;q11-12) and one case of a
      t(9;22;15)(q31;q12.2;q25). Thus, 5 out of 7 cases of EMC showed recombination
      between 9q22-31 and 22q11-12, indicating that this represents a tumor specific
      abnormality. The breakpoints on 22q were in all 5 cases cytogenetically
      indistinguishable from those seen in Ewing's sarcoma with t(11;22), clear-cell
      sarcoma with t(12;22), and desmoplastic small round cell tumors with t(11;22).
      Molecular cloning of these translocation breakpoints revealed involvement of the
      EWS gene (located at 22q12) in all 3 tumor types. These observations raise the
      intriguing question of whether the EWS gene might also be involved in the t(9;22)
      in EMC.

PMID- 7635567
TI  - Breast-cancer risk and oral contraceptive use in Slovenian women aged 25 to 54.
AB  - Results of a previous case-control study in Slovenia showed a significantly
      elevated risk of breast cancer for ever-OC users aged 25 to 54 years. A further
      study was conducted in 1988-1990 in the whole of Slovenia, employing more
      rigorous epidemiological methodology. Cases were 624 women with breast cancer,
      aged 25 to 54 years, diagnosed at the Institute of Oncology in Ljubljana and
      other Slovenian hospitals. Controls were 624 women identified through the
      Population Registry, randomly selected and matched with cases by date of birth
      and commune of residence. Data were collected by personal interview, using
      coloured photographs of packages of all OC on the Slovenian market since 1964. A
      calendar of reproductive life events was constructed with participants to improve
      estimation of exposure. The adjusted odds ratio (OR) for ever-users was 1.09.
      There was no increase in risk with total duration of use, interval since first
      use, age at starting OC, according to use before or after first delivery and time
      between menarche and age at first use. Increased risk (OR = 2.92) was found for
      OC users at the time of diagnosis and for those stopping them less than 6 months
      before (current users). The risk was not increased for those who stopped OC more
      than 6 months before diagnosis. The results of this study are consistent with
      most studies showing no overall effect of OC in women aged till 55 years ever
      using them. Increased risk of breast cancer in current OC users suggests a
      possible promoting effect of the pill in susceptible women, and indicates the
      need for careful breast surveillance of these women while they are using OC and
      in the period immediately following cessation.

PMID- 7635566
TI  - Expression and in-situ localization of genes coding for extracellular matrix
      proteins and extracellular matrix degrading proteases in pancreatic cancer.
AB  - Pancreatic cancer shows a strong desmoplastic reaction characterized by a
      remarkable proliferation of interstitial connective tissue (collagens type I and
      III, fibronectin). In this study we have analyzed the balance of expression of
      mRNAs encoding extracellular matrix components (collagens I, III and IV, laminin,
      fibronectin), extracellular matrix-degrading metalloproteinases (MMP-1, -2, -3
      and -9) and tissue inhibitors of metalloproteinases (TIMP-1 and -2) in pancreatic
      cancer and control pancreatic tissue by Northern-blot analysis and mRNA in situ
      hybridization. Transcripts for MMP-1 (interstitial collagenase) and MMP-3
      (stromelysin-1) were not detectable in pancreatic cancer and control tissues.
      Steady-state levels of transcripts encoding extracellular matrix proteins, MMP-2
      (72-kDa collagenase IV), MMP-9 (92-kDa collagenase type IV), TIMP-1 and TIMP-2
      were elevated in the majority of pancreatic-cancer tissue samples as compared to
      control pancreatic tissue. A good correlation was seen between overexpression of
      these MMPs and TIMPs and the steady-state levels of transcripts coding for
      extracellular matrix proteins, the amount of collagen protein and the severity of
      the desmoplastic reaction. In situ hybridization studies localized transcripts
      coding for collagens type I and III to spindle-shaped stromal cells, whereas
      transcripts for MMP-2, MMP-9, TIMP-1 and TIMP-2 were found in both stromal and
      tumor cells. However, MMP-2 transcripts appeared to be more abundant in stromal
      cells, TIMP-1 and TIMP-2 transcripts were evenly distributed over tumor and
      stromal cells and relatively more MMP-9 transcripts were found in tumor cells. We
      conclude that, in human pancreatic cancer, MMP-2, MMP-9, TIMP-1 and TIMP-2 may be
      involved in processes leading to the strong desmoplastic reaction observed in
      these tumors. Both stromal and tumor cells appear to be the source of MMPs and
      TIMPs in human pancreatic cancer.

PMID- 7635568
TI  - Effects of 1,25-dihydroxyvitamin D3 on transformed C3H/10T1/2 fibroblasts grown
      as multicellular spheroids.
AB  - We have previously shown that 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) is able to
      modulate proliferation of C3H/10T1/2 fibroblasts grown in monolayer cell culture.
      The aim of this study was to investigate the effects of the hormone in a 3
      dimensional culture system, which is considered to better reflect the cellular
      environment that is found in vivo. Two transformed cell lines of C3H/10T1/2
      fibroblasts (C116 and TPA 482) were grown as multicellular spheroids, whereas the
      nontumorigenic C3H/10T1/2 C18 cells failed to form spheroids. The hormone had no
      effect on spheroids made of TPA 482 cells but had a biphasic effect on C116
      spheroid growth with stimulation at low and inhibition at higher concentrations.
      In C116 spheroids, 10(-8) M 1,25-(OH)2D3 induced complete arrest of spheroid
      growth. Light and electron microscopic studies and immunocytochemistry showed
      that 10(-8) M 1,25-(OH)2D3 induced morphological changes in C116 spheroids, with
      a marked reduction in expression of fibronectin, laminin and the gap junction
      protein connexin 43. These effects were followed by a loosening of the spheroid
      structure, detachment of viable cells, and finally disaggregation of the
      spheroids. The results of this study, together with the data previously obtained
      in monolayer cell cultures, indicate that the effects of 1,25-(OH)2D3 may be
      conditioned by the cellular environment. Therefore, the spheroid model is an
      interesting tool for investigation of the antineoplastic effect of the hormone.

PMID- 7635569
TI  - Comparison of solutol HS 15, Cremophor EL and novel ethoxylated fatty acid
      surfactants as multidrug resistance modification agents.
AB  - Some well-known fatty acid ester surfactants, e.g., Cremophor EL and Solutol HS
      15, are modulators of multidrug resistance in vitro and in vivo. Because they are
      polydisperse, and their active component(s) have not been identified, the
      therapeutic potential of such surfactants is unclear. To better define the active
      components of Solutol HS 15 and to make more potent surfactant multidrug
      resistance modulators, highly purified C-18 fatty acids were esterified with
      ethylene oxide at 5-200 molar ratios. Unexpectedly, ethylene oxide esters of pure
      12-hydroxy stearic acid, the major components of Solutol HS 15, displayed
      negligible resistance modification activity compared with Solutol HS 15 itself or
      to stearic and oleic acid esters synthesized under identical conditions. Since
      oleic acid esters appeared to have good activity, a series of these compounds was
      prepared to determine the optimal ethylene oxide/fatty acid ratio. The optimal
      ratio was found to be 20 mole ethylene oxide: I mole fatty acid, with a steep
      decline in activity for products made with ratios above and below the optimum.
      The most active oleic acid ester, designated CRL 1337, was 8.4-fold as potent as
      Solutol HS 15 and over 19-fold as potent as Cremophor EL in promoting rhodamine
      123 accumulation in multidrug-resistant KB 8-5-11 cells in vitro. Our results
      show that the structure of the hydrophobic domain (fatty acid) of surfactants as
      well as its hydrophile-lipophile balance are critical in determining the potency
      of surfactants as reversing agents.

PMID- 7635570
TI  - Apoptosis in human lymphoblastoid cells induced by acivicin, a specific gamma
      glutamyltransferase inhibitor.
AB  - We examined the effects of acivicin, a specific inhibitor of the ectoenzyme gamma
      glutamyltransferase (gamma-GT), on gamma-GT activity and apoptosis in 2 human T
      lymphoblastoid CEM cell lines, CCRF and VBL-100. In both cell lines, acivicin was
      found to cause morphological and biochemical changes of apoptosis in a dose
      dependent manner. There was a close correlation between inhibition of gamma-GT
      activity and the emergence of apoptotic cells. However, VBL-100 cells had a 50%
      higher gamma-GT basal activity than CCRF-CEM cells, their enzyme activity was
      more inhibited, and, they had a greater apoptotic response to acivicin. The gamma
      GT-specific activity in apoptotic/dead cells was also almost totally inhibited,
      while that of cells that remained alive after 5 days of acivicin treatment was
      not. These findings confirm that gamma-GT is implicated in the process of
      apoptosis of CEM cells.

PMID- 7635571
TI  - Comparison of protein kinase C activity and isoform expression in cisplatin
      sensitive and -resistant ovarian carcinoma cells.
AB  - Cellular sensitivity to cis-diamminedichloroplatinum(II) (cDDP) can be regulated
      by protein kinase C (PKC) signal transduction pathway. Activators of PKC were
      shown to enhance the sensitivity of human ovarian carcinoma 2008 cells to cDDP.
      We have examined whether or not the PKC signal transduction pathway is affected
      during development of resistance by tumor cells to cDDP. A 2-fold decrease in PKC
      activity was observed in cDDP-resistant ovarian carcinoma 2008/C13*5.25 cells
      compared with the drug-sensitive 2008 cells. Subcellular distribution studies
      revealed a reduction in both cytosolic and particulate PKC activities in
      2008/C13*5.25 cells. The pattern of PKC isoform expression was compared in cDDP
      sensitive and -resistant cell lines by Western blot analysis with isoform
      specific antibodies to PKC. The parental cells expressed PKC alpha, -epsilon, and
      -zeta isoforms. The abundance of PKC alpha decreased significantly in
      2008/C13*5.25 cells, whereas the amount of PKC epsilon increased moderately in
      the resistant variant, with no alteration in PKC zeta content. Therefore, a
      reduction in PKC alpha and/or an increase in PKC epsilon expression may be
      associated with the drug-resistant phenotype.

PMID- 7635573
TI  - Tumor-reactive superantigens suppress tumor growth in humanized SCID mice.
AB  - Superantigens are extremely potent activators of T lymphocytes. To develop a
      tumor-reactive superantigen for cancer therapy, we made a recombinant fusion
      protein of the superantigen staphylococcal enterotoxin A (SEA) and the Fab region
      of the C242 monoclonal antibody (C242Fab-SEA), which recognize human colon
      carcinoma cells. The therapeutic effect of C242Fab-SEA on colon-cancer growth was
      examined in lymphocyte-engrafted humanized SCID mice bearing intraperitoneally
      growing Colo205 colon carcinomas. i.v. injections of C242Fab-SEA significantly
      inhibited tumor growth. The anti-tumor effect required the presence of human T
      cells in the SCID mice. Optimal therapeutic effects were seen with C242Fab-SEA,
      but not with C242Fab fragment or SEA alone, demonstrating that both entities of
      the fusion protein were required. C242Fab-SEA-treated tumors showed a massive
      infiltration of T cells in the tumor parenchyme, and was accompanied by enhanced
      expression of ICAM-I and HLA-DR on the tumor cells. The results demonstrate that
      Fab-SEA fusion proteins convey superantigenicity on tumor cells which evoke T
      cell-dependent suppression of tumor growth.

PMID- 7635574
TI  - The epithelial/carcinoma antigen EGP-1, recognized by monoclonal antibody RS7
      3G11, is phosphorylated on serine 303.
AB  - RS7-3G11 is a murine monoclonal antibody (MAb) raised against human non-small
      cell lung carcinoma, and is under clinical evaluation. The epithelial/carcinoma
      antigen EGP-1, defined by RS7-3G11, was isolated and purified to homogeneity from
      a cervical carcinoma cell line, ME180. EGP-1 is a glycoprotein with an average
      molecular mass of 47.8 kDa. Metabolic labeling of the antigen with 32P
      orthophosphate and subsequent immunoprecipitation with RS7-3G11 showed that it is
      a phosphoprotein. Phosphoamino acid analysis of the in vivo phosphorylated EGP-1
      revealed that the phosphorylation is on serine. In vitro analysis with purified
      antigen demonstrated that protein kinase C, and not protein kinase A, is involved
      in phosphorylating the antigen in vitro. In vitro analysis indicated a
      stoichiometry of phosphorylation of 0.54 mole of phosphate per mole of EGP-1.
      Phosphoamino acid analysis and phosphopeptide mapping of the antigen
      phosphorylated in vitro by protein kinase C showed that phosphorylation occurred
      on a serine residue, specifically on serine 303, located in the cytoplasmic
      domain of EGP-1. Treatment of ME180 cells with phorbol ester increased the
      phosphorylation of EGP-1. The biological function of EGP-1 remains to be
      elucidated. In this report we elucidate an involvement of protein kinase C in
      phosphorylating EGP-1, which may signify a role for this antigen in signal
      transduction across the cell membrane.

PMID- 7635572
TI  - RB and a novel E2F-1 binding protein in MHC class II deficient B-cell lines and
      normal IFN-gamma induction of the class IL transactivator CIITA in class II non
      inducible RB-defective tumor lines.
AB  - The major histocompatibility (MHC) class II genes encode cell surface proteins
      that bind antigenic peptide for presentation to T-cells. The class II proteins
      are expressed constitutively on B-cells and EBV-transformed B-cells, and are
      inducible by IFN-gamma on a wide variety of cell types. Retinoblastoma protein
      (RB) is a tumor suppressor and functions as a transcriptional repressor by
      binding and inactivating the transactivator E2F-I. RB-defective tumor lines are
      non-inducible for MHC class II by IFN-gamma, or very weakly inducible, but
      transfection of 2 different lines with RB expression vectors re-establishes or
      substantially enhances class II inducibility. Therefore, we examined the RB
      status of a series of B-cell mutants that are defective in class II expression,
      generated either in vitro or derived from Bare Lymphocyte Syndrome (BLS)
      patients. Nuclear matrix-bound RB was detectable in all cases, indicating that
      loss of RB is not responsible for decreased class II expression in these lines. A
      second E2F-I binding protein, most likely DP-I, was also apparently normal in
      both class II-positive and -negative B-cell lines. We also examined the IFN-gamma
      induction of CIITA in RB-defective lines. CIITA is a class II gene transactivator
      known to be defective in one form of BLS and to be required for the induction of
      MHC class II by IFN-gamma. CIITA mRNA is normally inducible by IFN-gamma in class
      II non-inducible, RB-defective lines, and in one line, re-expression of RB has no
      effect on CIITA mRNA induction levels. Thus, the block in MHC class II
      inducibility in RB-defective cells is not due to a block in CIITA inducibility.

PMID- 7635575
TI  - The pure antiestrogen ICI 182,780 binds to a high-affinity site distinct from the
      estrogen receptor.
AB  - Both estrogen receptor-positive (ER+), tamoxifen-sensitive (5-21) and tamoxifen
      resistant (5-23) subclones of the parental MCF-7 breast cancer cell line were
      used in competitive ligand binding studies involving either [3H]ICI 182,780 or 4
      OH-[3H]tamoxifen (4OHT) displacement by unlabelled estradiol (E2) or the
      antiestrogens (AE) 4OHT and ICI 182,780. Neither radioligand was displaced
      significantly by E2 over a range of concentrations; binding was predominantly
      inhibited by the corresponding radio-inert ligand. Scatchard analysis of the data
      revealed that the binding capacities of both cell lines for ICI 182,780 were
      approximately 7-fold greater than the previously determined number of ER sites
      per cell, with the affinity being an order of magnitude less than that of E2 for
      ER. No difference was found between the TAM-sensitive and -resistant cells in
      their binding of either AE. When cells were preincubated with either E2, TAM or
      4OHT at a high, fixed concentration to block the ER or AE binding sites (AEBS),
      respectively, displaceable binding of [3H]ICI 182,780 was still observed,
      indicating binding at a site other than the classical ER or previously described
      AEBS. Our results suggest that there is a specific, saturable and relatively high
      affinity binding site for ICI 182,780 in MCF 5-21 and MCF 5-23 breast cancer
      cells. However, the physiological relevance of this binding site requires further
      clarification because in cell growth assays, E2 (at 1/10 the dose of ICI 182,780)
      overcame the inhibitory effect of the antiestrogen in both of the cell lines.

PMID- 7635576
TI  - Biochemical and growth-modulatory effects of the new S-adenosylmethionine
      decarboxylase inhibitor CGP 48664 in malignant and immortalized normal human
      breast epithelial cells in culture.
AB  - CGP 48664 [4-aminoindanon-1-(2'-amidino)hydrazone dihydrochloride monohydrate] is
      a newly introduced inhibitor of S-adenosylmethionine decarboxylase (SAMDC) with
      increased selectivity of action and reduced toxicity. We analyzed the biochemical
      and antiproliferative effects of this compound in a panel of hormone-dependent (3
      clones of MCF-7, T47D) and -independent (MDA-MB-231, BT-20) human breast cancer
      cell lines in culture. For comparison, we also tested its effects in the
      spontaneously immortalized human breast epithelial cell line MCF-10A. All cell
      lines were highly sensitive to the growth-inhibitor effect of CGP 48664 with an
      IC50 between 0.1 and 0.5 microM. A dose-dependent bell-shaped increase in SAMDC
      was observed in normal and malignant breast cells resulting from enzyme
      stabilization by the inhibitor as supported by Western blot analysis. While
      ornithine decarboxylase (ODC) activity consistently increased, the effect of CGP
      48664 on spermidine/spermine N'acetyltransferase (SSAT) was variable in the
      breast cancer cell lines. In contrast, the inhibitor consistently reduced SSAT
      activity level in the MCF-10A cell line and its derivative partially transformed
      by a mutated ras oncogene. As expected cellular putrescine levels were markedly
      increased by CGP 48664 administration, whereas spermidine and spermine contents
      were reduced. However, the degree of reduction was usually only moderate.
      Furthermore, exogenous polyamine administration was relatively ineffective in
      rescuing the antiproliferative effect of CGP 48664 in MCF-7 cells, while exerting
      a more complete rescue in the MDA-MB-231 cell line. We conclude that CGP 48664
      exerts a potent growth-inhibitory effect on mammary cells in culture. However,
      its action may not always be entirely mediated through the polyamine pathway.

PMID- 7635578
TI  - The treatment of incest offenders--a hypnotic approach: a brief communication.
AB  - Incest has become more prominent in public awareness over the past 15 years. The
      major focus of this interest has been on the incest survivor. The incest offender
      has received less attention. A hypnotic approach to treating incest offenders is
      outlined that involves a seven-stage approach. A case example is presented and
      future research directions suggested.

PMID- 7635577
TI  - Pro-transforming growth factor-alpha processing in human colon carcinoma cells:
      role of protein kinase C.
AB  - The human colon cancer cell lines HCT 116 (poorly differentiated) and GEO (well
      differentiated) express the mitogenic peptide transforming growth factor alpha
      (TGF-alpha). The secretion of TGF-alpha was enhanced by phorbol 12-myristate 13
      acetate (PMA), indicating the possible role of protein kinase C (PKC) in the
      formation of mature TGF-alpha. Cells were metabolically labeled with 35S-cysteine
      and the formation of the mature 6 kDa TGF-alpha polypeptide from the 17 kDa pro
      TGF-alpha precursor was determined. The conversion of pro-TGF-alpha was complete
      in 2-4 hr with the HCT 116 cells showing faster kinetics of TGF-alpha formation
      than GEO cells. HCT 116 cells secreted more TGF-alpha than GEO cells and the rate
      and extent of formation of TGF-alpha was enhanced by PMA in both cell lines. The
      expression of several PKC isozymes by HCT 116 and GEO cells was examined by
      immunoblotting. The expression of all isozymes examined was higher in HCT 116
      cells compared with GEO cells. Calphostin C, an inhibitor of PKC, reduced the
      enzyme activity and significantly inhibited the PMA-induced secretion of TGF
      alpha by both cell lines. Two agonists of PKC that act on specific PKC isozymes,
      thymeleatoxin and 12-deoxyphorbol 13-phenylacetate 20-acetate (dPPA), stimulated
      the release of TGF-alpha into the medium to the same extent as PMA. Since dPPA
      has been reported to stimulate PKC-beta 1 specifically, our results suggest a
      potential role for PKC-beta in the processing of pro-TGF-alpha by these 2 human
      colon carcinoma cell lines.

PMID- 7635579
TI  - Hypnotic induction of an epileptic seizure: a brief communication.
AB  - This case study investigated the utility of hypnosis to precipitate a seizure in
      a patient with refractory epilepsy. The patient was twice administered a hypnotic
      induction and a suggestion to age regress to a day when he was distressed and
      suffered repeated seizures. The patient did not respond to the first hypnotic
      suggestion; however, an epileptic seizure was observed in the second hypnotic
      session. Videorecording and subdural electroencephalograph recording confirmed
      that he suffered an epileptic seizure. Postexperimental inquiry revealed that the
      patient used deliberate cognitive strategies to avoid seizure onset in the first
      session but adopted a more constructive cognitive style in the second session.
      Findings are discussed in terms of emotions, hypnosis, and cognitive style as
      mediating factors in the experimental precipitation of epileptic seizures.

PMID- 7635581
TI  - Attention-related electroencephalographic and event-related potential predictors
      of responsiveness to suggested posthypnotic amnesia.
AB  - Higher frequency electroencephalographic (EEG) activity around 40 Hz has been
      shown to play a role in cognitive functions such as attention. Furthermore, event
      related brain potential (ERP) components such as N1 and P1 are sensitive to
      selective attention. In the present study, 40-Hz EEG measures and early ERP
      components were employed to relate selective attention to hypnotic response.
      Participants were 20 low hypnotizable individuals, half assigned as simulators,
      and 21 high hypnotizable individuals. Each of these groups was subsequently
      divided into two groups based on recognition amnesia scores. The four groups
      differed in 40-Hz (36-44 Hz) EEG spectral amplitude recorded during preinduction
      resting conditions but not in EEG amplitude postinduction. The groups also
      differed in N1 amplitudes recorded during hypnosis. Regression analysis revealed
      that these effects only distinguish the high hypnotizable participants who
      experienced recognition amnesia from all other groups. The findings support the
      role of selective attention in hypnotic responsiveness, and the utility of
      subdividing high hypnotizable individuals is discussed.

PMID- 7635582
TI  - Hypnotic responsivity of the deaf: the development of the University of Tennessee
      Hypnotic Susceptibility Scale for the Deaf.
AB  - The purpose of these two studies was to develop and test a measure that assesses
      the hypnotic responsivity of deaf individuals. The University of Tennessee
      Hypnotic Susceptibility Scale for the Deaf (UTHSS:D) is a signed, videotaped
      version of a standard hypnotic induction with 12 standard suggestions. Experiment
      1 compared the behavioral and subjective hypnotic responsivity of deaf and
      hearing individuals using the UTHSS:D and the Field Depth Inventory (FDI),
      respectively. As compared to hearing subjects, deaf participants were found to be
      less responsive to hypnosis when assessed behaviorally (UTHSS:D) and equally
      responsive to hypnosis when assessed subjectively (FDI). Experiment 2 undertook a
      more comprehensive examination of the hypnotic responsivity of deaf individuals,
      using hearing individuals as controls. Three dimensions of hypnosis responsivity
      were assessed: behavioral (UTHSS:D), subjective (FDI), and interpersonal (Archaic
      Involvement Measure). Additionally, correlates of hypnotic responsivity
      (absorption, attitudes, expectations) were examined for the two groups. In
      Experiment 2, no significant differences were found between the deaf and hearing
      participant groups on any measures of hypnotic responsivity or on any measure of
      the correlates of hypnotic responsivity.

PMID- 7635580
TI  - Pre- and perioperative suggestion in maxillofacial surgery: effects on blood loss
      and recovery.
AB  - The basic assumption underlying the present study was that emotional factors may
      influence not only recovery but also blood loss and blood pressure in
      maxillofacial surgery patients, where the surgery was performed under general
      anesthesia. Eighteen patients were administered a hypnosis tape containing
      preoperative therapeutic suggestions, 18 patients were administered hypnosis
      tapes containing pre- and perioperative suggestions, and 24 patients were
      administered a hypnosis tape containing perioperative suggestions only. The
      patients who received taped suggestions were compared to a group of matched
      control patients. The patients who received preoperative suggestions exhibited a
      30% reduction in blood loss. A 26% reduction in blood loss was shown in the group
      of patients receiving pre- and perioperative suggestions, and the group of
      patients receiving perioperative suggestions only showed a 9% reduction in blood
      loss. Lower blood pressure was found in the groups that received pre- and
      perioperative and perioperative suggestions only. Rehabilitation was facilitated
      in the group of patients receiving perioperative suggestions only.

PMID- 7635583
TI  - Organization and functioning of ISCEH, The International Society for Clinical and
      Experimental Hypnosis.
AB  - The first international society of hypnosis founded in this century, the
      International Society for Clinical and Experimental Hypnosis (ISCEH), was
      organized in 1958 as a direct result of societal conflicts between The Society
      for Clinical and Experimental Hypnosis (SCEH) and the American Society of
      Clinical Hypnosis (ASCH). Initially, it consisted of National Divisions built
      around key contributors in 30 different countries. This article describes the
      inception, organization, and development (including controversies and conflicts)
      of ISCEH up to 1973. At that time, through the cooperation of SCEH, ASCH, and
      other international groups, under the leadership of Dr. Ernest R Hilgard, ISCEH
      was reorganized, reconstituted, and renamed The International Society of Hypnosis
      (ISH). For the purpose of historical study, the society's voluminous
      correspondence, directories of officers and committees, awards, photographs,
      programs of congresses, election records, and other relevant documents have been
      cataloged and preserved in some 82 files in the Archives of the History of
      American Psychology at the University of Akron, Akron, Ohio.

PMID- 7635584
TI  - Cancer mortality among Chinese migrants: a review.
AB  - BACKGROUND: Epidemiological studies of cancer among migrant groups are beneficial
      in that they can provide insight into genetic and environmental factors in
      disease aetiology. Seven studies in the epidemiological literature have examined
      cancer mortality in migrants from China; methodological features and findings,
      which display remarkable consistencies between studies, are reviewed here.
      METHODS: Papers were included that compare site-specific cancer mortality
      patterns in first and second generation migrants to the experience in the host
      regions using vital statistics and census data. Rates had to be standardized
      either indirectly (using age-specific rates from the host regions) or directly
      (using a standard age structure) and standardized mortality ratios (SMR) or rate
      ratios (RR) were calculated. RESULTS: Migrant males had overall mortality from
      cancer that was often in significant excess compared to the host experience;
      results for females (for overall cancer) were equivocal. Both sexes had large and
      significant excess mortality from nasopharyngeal and liver cancer; SMR and RR
      were also consistently elevated for cancers of the stomach and oesophagus. There
      was notable attenuation in the high risk at these four sites in the second
      generation. All studies reported pronounced and significant reduced risk for
      prostatic cancer and female breast cancer, with little or no increase in
      mortality in the second generation. The SMR and RR also tended to be below unity
      for brain, bladder and kidney cancer. CONCLUSIONS: The results of this review
      indicate that cancer risk at several sites among Chinese migrants appears to be
      in transition, and that these findings are consistent across studies.

PMID- 7635585
TI  - Cancer incidence and mortality among beta-naphthylamine and benzidine dye workers
      in Moscow.
AB  - BACKGROUND: Cancer incidence and mortality were evaluated among 4581 aniline dye
      production workers in Moscow. METHODS: A historical cohort was assembled and
      followed-up from 1 January 1975 to 31 December 1989. Moscow district oncologic
      dispensary registries furnished case ascertainment and employer records provided
      job exposure data. Expected cancers and deaths were calculated based on gender-,
      age-, and calendar time-specific incidence and mortality rates for the Moscow
      general population applied to the cohort's person-years of follow-up. Disease
      specific standardized mortality and incidence values were derived from ratios of
      observed to expected cancers. RESULTS: Men experienced elevated total cancer
      mortality (standardized mortality ratio [SMR] = 125; 95% CI: 110-142) and urinary
      bladder cancer mortality (SMR = 279; 95% CI: 192-391), and increased all
      malignancy (standardized incidence ratio [SIR] = 142; 95% CI: 125-160),
      oesophageal (SIR = 203; 95% CI: 108-347), respiratory tract (SIR = 154; 95% CI:
      120-194) and bladder (SIR = 394; 95% CI: 268-559) cancer incidence. Women had
      elevated oesophageal (SMR = 313; 95% CI: 124-664) and bladder (SMR = 311; 95% CI:
      149-571) cancer mortality and elevated all malignancy (SIR = 124; 95% CI: 106
      144), oesophageal (SIR = 348; 95% CI: 140-719), and bladder (SIR = 861; 95% CI:
      458-8002) cancer incidence. Bladder cancer rate increased with employment
      duration and younger age first hired. Rate estimates were highest among beta
      naphthylamine exposed workers but was also increased among workers with other
      chemical exposures. A cancer prevention and control effort that limited benzidine
      exposure to < or = 3 years was apparently unsuccessful as indicated by a
      significant excess of bladder cancer (SIR = 1773; 95% CI: 356-5180) among these
      workers. CONCLUSION: Relative rates of oesophageal, lung, and stomach cancer were
      also elevated among all workers, but did not increase with total years worked,
      age first hired, or year first hired, suggesting a non-occupational aetiology.

PMID- 7635586
TI  - Cancer incidence in a group of workers potentially exposed to ethylene oxide.
AB  - BACKGROUND: Cytogenetic changes associated with ethylene oxide (ETO) exposure at
      a worksite prompted a study of cancer incidence in that cohort. METHOD: Cancer
      incidence through 31 December 1987 was ascertained in a cohort of 1132
      individuals employed at the worksite at any time from 1 July 1974 through 30
      September 1980, the period of potential exposure to ETO at the plant. The number
      of observed cancers was compared with that expected based on age- and sex
      specific incidence rates reported by the National Cancer Institute's Surveillance
      Epidemiology and End Results Program. Standardized morbidity ratios (SMR) were
      calculated separately for regular and temporary employees. RESULTS: Of the 28
      cancers observed in the cohort, 12 were breast cancers. The SMR for breast cancer
      among regular female employees ranged from 2.55 (95% CI: 1.31-4.98, P = 0.02) to
      1.70 (95% CI: 0.89-3.23, P = 0.09) depending on calendar year of follow-up,
      assumptions about completeness of follow-up, and the reference rates used. The
      excess of breast cancer over expected in regular female employees diminished over
      time. No statistically significant excess of breast cancer was noted for
      temporary female employees at any point during follow-up. No increase in cancer
      incidence was found over that expected for any cancer sites associated with ETO
      in previous studies--leukaemia, brain, pancreas and stomach. CONCLUSIONS: Factors
      such as appropriateness of latency periods, length of follow-up and lack of a
      common histopathological type need to be considered in evaluating the excesses in
      observed breast cancer incidence, which diminished over time.

PMID- 7635587
TI  - Epidemiology of breast cancer in Japan.
AB  - BACKGROUND: A recent increase in the numbers of deaths and incident cases of
      breast cancer among Japanese women stimulated the authors to summarize the trends
      in female breast cancer mortality and incidence rates in Japan. METHODS: The
      number of deaths from female breast cancer was obtained from the national vital
      statistics. Estimated incidence rates, based on several cancer registries, were
      also used for the analyses. The trends in the age-adjusted and age-specific rates
      were examined. Age and birth cohort effects on the incidence and mortality rates
      were examined, using multiplicative models. RESULTS: The age-adjusted mortality
      rate has been increasing since the 1960s (4.1 per 100,000 population in 1950 and
      6.6 in 1991, adjusted by the World Population). The age-adjusted incidence rate
      has also been rising since 1975. Age-specific rates have been increasing
      particularly in the age range 40-79 years. The multiplicative models disclosed an
      increasing cohort effect for the mortality and incidence rates among women born
      after 1900. Decreasing mortality and incidence rates after menopause were
      ascribed by the models to strong cohort effects. CONCLUSIONS: The recently
      increasing trend was believed to be consistent with changed risk factors among
      Japanese women. The age effect on female breast cancer incidence rate in Japan
      was concluded to be similar to that in Western populations.

PMID- 7635588
TI  - A case-control study of risk factors for breast cancer in Brazil, 1978-1987.
AB  - BACKGROUND: There are still controversies regarding the role of many risk factors
      assessed for breast cancer worldwide. In Brazil, it represents a major cause of
      death among women but yet few analytical studies have been published to date.
      METHODS: The association of selected factors with breast cancer was assessed in a
      case-control study of 300 women, aged 25-75 years, treated at the Federal
      University Hospital, Belo Horizonte, Brazil, from 1978 to 1987. In all, 300 cases
      with diagnosed breast carcinoma were compared with 600 controls matched on age
      and date of diagnosis. Socio-economic, demographic and reproductive factors were
      analysed. RESULTS: Multiple logistic regression analysis showed the following
      factors to be independently associated with increased risk of breast cancer: a)
      monthly family income (odds ratio [OR] = 1.69, 95% confidence interval [CI]: 1.18
      2.42); b) being a housewife (OR = 2.86, 95% CI: 1.83-4.47; c) parity of less than
      six deliveries and nulliparous women (OR = 5.06, 95% CI: 3.01-8.52 and OR = 2.42,
      CI: 1.64-3.59, respectively); d) history of breast cancer among first degree
      female relatives (OR = 9.35, 95% CI: 3.22-27.14); and e) oral contraceptive use
      (OR = 1.81, 95% CI: 1.15-2.85). Irregular menstrual cycle (OR = 0.44, 95% CI:
      0.25-0.75) was associated with breast cancer as a protective effect. CONCLUSIONS:
      The study has confirmed most risk/protective factors previously demonstrated
      elsewhere in the world and provides clear documentation of breast cancer
      epidemiology in Brazil.

PMID- 7635589
TI  - Duration of preclinical cervical cancer and reduction in incidence of invasive
      cancer following negative pap smears.
AB  - BACKGROUND: An investigation has been made into the differences between estimates
      for the duration of preclinical cervical cancer resulting from two types of
      studies. A median duration of 5-10 years was suggested by the observed build-up
      of incidence of invasive cervical cancer after one or more negative smears. Much
      longer median durations of more than 15 years have been reported from fitting
      statistical models to screening data. METHODS: We developed one of these
      statistical models and fitted it to clinical incidence and screening data from
      British Columbia, which resulted in estimated mean durations of 12 years for pre
      invasive stages, and 4-5 years for screen-detectable stages. The model is used to
      predict the build-up of the incidence of invasive cancer after one and after two
      negative smears. RESULTS: The model predictions appear to correspond closely to
      the observed incidence trends following negative smears. The apparent
      contradiction between model estimates and observed data is explained by
      recognizing that many of the women who have had negative smears will have further
      Pap smears, resulting in earlier diagnosis of invasive cervical cancers and thus
      an apparent faster build-up of the incidence. CONCLUSIONS: When the impact of
      further Pap smears is neglected, the data suggest that the risk of invasive
      cancer following one or more negative smears returns to close to prescreening
      levels within 6-10 years. This is an overestimation of the risk of clinical
      invasive cancer. In the case of cessation of screening it will take longer before
      the incidence of clinical cancer will increase. Where there is continuous
      screening the screen-detected cancers have a relatively favourable prognosis,
      thus contributing less to the serious morbidity and mortality risks associated
      with invasive cancer. This should be taken into account in making comparisons
      with the prescreening situation.

PMID- 7635590
TI  - Maternal exposure to N-nitrosatable drugs as a risk factor for childhood brain
      tumours.
AB  - BACKGROUND: Animal models suggest that compounds containing a nitrosyl group (N
      nitroso compounds (NNO)) can act as potent transplacental carcinogens. Many
      common drug formulations have the potential to undergo nitrosation in vivo. The
      association between maternal use of nitrosatable drugs during pregnancy and
      development of brain tumours in the offspring was examined in a SEER-based case
      control study. METHODS: Maternal exposure to nitrosatable drugs during pregnancy
      was compared among 361 childhood brain tumour cases and 1083 matched controls
      recruited through random-digit dialing. RESULTS: There was no increase in risk
      observed for childhood brain tumours overall (OR = 1.15; 95% CI: 0.69-1.94) or
      for astrocytomas individually (OR = 1.16; 95% CI: 0.50-2.69). A slight elevation
      in risk was noted for medulloblastomas (OR = 1.47; 95% CI: 0.28-7.62) and 'other'
      tumours (OR = 1.27; 95% CI: 0.56-2.86), however, both estimates were based on
      small numbers. CONCLUSIONS: Our findings suggest that no increased risk of
      childhood brain tumours was associated with maternal exposure to nitrosatable
      drugs. The study results should be viewed with caution given the imprecision of
      the point estimates as well as the lack of data on specific timing and dosage of
      exposure and degree of nitrosatability of drugs taken.

PMID- 7635591
TI  - Dietary patterns and cardiovascular risk factors in elderly men: the Zutphen
      Elderly Study.
AB  - BACKGROUND: We investigated whether dietary patterns were associated with
      cardiovascular risk factors in 518 elderly men (70-89 years), using data from the
      30-year follow-up survey of the Zutphen Study. METHODS: Dietary intake was
      estimated by cross-check dietary history. We used cluster analysis to aggregate
      individuals into four groups, characterized by high alcohol intake, high meat
      consumption, healthy dietary pattern, and high intake of refined sugars. RESULTS:
      In the alcohol cluster socioeconomic status was higher (P < 0.05) than in the
      meat cluster. High density lipoprotein (HDL)-cholesterol was 0.15-0.23 mmol/l
      higher (P < 0.05) in the alcohol cluster compared to the other clusters.
      Furthermore, in the meat cluster HDL-cholesterol was 0.08 mmol/l higher than in
      the refined sugars cluster (P < 0.05). Total serum cholesterol was 0.26 mmol/l
      higher in the meat cluster compared to the healthy diet cluster (95% CI: -0.17,
      0.69). The prevalence of hypertension was almost 10% higher in alcohol cluster
      compared to the other three clusters (95% CI: -3, 23). The percentage of non
      smokers was highest in the healthy diet cluster. These results were irrespective
      of potential confounders, such as age, body mass index, socioeconomic status,
      smoking, and being on a prescribed diet. CONCLUSIONS: The effects of moderate
      alcohol intake on cardiovascular risk factors are confirmed in elderly men.
      Furthermore, a healthy diet is associated with more favourable levels of
      cardiovascular risk factors at old age.

PMID- 7635592
TI  - Attitudes and ischaemic heart disease in the Caerphilly Study: the Health
      Attitude Inventory.
AB  - BACKGROUND: The Health Attitude Inventory (HAI) is developed to assess attitudes,
      beliefs and values towards coronary-related behaviour in epidemiological studies.
      It comprises a 76-item self-administered questionnaire which can be completed in
      under 10 minutes by most adults. METHODS: The HAI was administered to 2100 men
      aged 50-64 years along with measures of ischaemic heart disease risk factors,
      including the following coronary-related behaviours: smoking, exercise, type A
      behaviour and the consumption of fried food, dairy produce, wholemeal bread and
      vegetables. RESULTS: Cross-sectional analyses using linear regression showed
      attitudes, beliefs and values to explain between 8% and 27% of the variance in
      the dietary coronary-related behaviour. For exercise 13% of the variance was
      explained, and for type A behaviour 18%. Similar analysis for smoking using
      logistic regression (non-smoker versus current smoker) showed a predictive
      concordance of 95%. CONCLUSIONS: The HAI has demonstrated the assessment of
      attitudes, beliefs and values in an epidemiological setting to show associations
      with a range of coronary risk behaviours. This finding has potential public
      health as well as aetiological application in that influential attitudes, values
      and beliefs can be identified to aid increasing healthy as well as reducing risky
      coronary-related behaviour.

PMID- 7635595
TI  - The association of smoking and drinking habits with serum pepsinogens.
AB  - BACKGROUND: The influence of smoking on serum pepsinogen I has been assessed.
      However, still to be assessed are the influences of smoking on pepsinogen II and
      drinking on serum pepsinogens. METHODS: Data were collected from 13,381 employees
      by questionnaire and serum tests. Multiple regression analyses were done with
      logarithms of serum pepsinogen I (LPI), pepsinogen II (LPII) or pepsinogen I/II
      ratio (LI/II) as a criterion variable and as categorized explanatory variables,
      sex, age, subjective symptoms in the stomach, past history of peptic ulcer,
      current smoking dose, past smoking amount, drinking habit and current drinking
      dose. RESULTS: Current smoking dose showed dose-dependent positive associations
      with LPI and LI/II: Past smoking amount yielded weakly dose-dependent negative
      associations with LPI and LI/II: Current drinking dose showed dose-dependent
      negative associations with LPI and LPII. CONCLUSION: Current smoking elevates
      pepsinogen I and the I/II ratio, and it may be necessary to consider the effect
      of smoking when pepsinogens are used as markers for gastric cancer. Drinking
      reduced pepsinogen I and II, but the effect was not so large.

PMID- 7635593
TI  - Premature cardiovascular mortality in France: divergent evolution between social
      categories from 1970 to 1990.
AB  - BACKGROUND: In France, differences in cardiovascular risk factor distribution
      have been observed which might be responsible for some disparities in
      cardiovascular mortality between social categories. The goal of the study was
      thus to assess the differences in coronary heart disease (CHD) and
      cerebrovascular diseases (CVD) mortality according to social category, and to
      determine their trends over the last 20 years in France. METHODS: Mortality data
      for CHD, CVD, diseases of the circulatory system (CS) and all causes mortality
      (TM) were based on death certificates for 1970, 1980 and 1990, and categorized by
      sex, age group (35-44 and 45-54 years), region and social category. RESULTS:
      Among active men, from 1970 to 1990, the overall decrease observed for all causes
      of death was significantly slower among employees and workers for CHD, CS and TM
      (P < 0.001), but not for CVD. In 1990, the highest mortality rates were observed
      among employees and workers for CHD, CVD and CS mortality. In women, no such
      trend was observed for CHD, CVD or CS mortality. No statistically significant
      difference between social categories was observed in 1990 for CHD and CVD. In the
      whole active population, a negative trend for the mortality rates was observed
      between 1970 and 1990 whatever the cause in both sexes. The ratio between
      mortality rates among non-active versus active people increased during the two
      decades in both sexes. CONCLUSIONS: In men, the inequalities have increased over
      the last two decades for CHD and have not been reduced for CVD. The category of
      employees and workers were found to be at special risk for premature
      cardiovascular disease mortality. Among women, the trends were less clear,
      although the tendencies were the same. An increasing disparity between active and
      non-active people suggests that a health-related selection process towards
      unemployment might have contributed to the decreasing mortality rates observed
      among employees and workers.

PMID- 7635597
TI  - Social inequality in mortality in Sao Paulo State, Brazil.
AB  - BACKGROUND: Epidemiological studies have consistently demonstrated social
      inequality to be an important factor in the distribution of illness and death in
      society. However, little work has been published on social differentials in
      mortality in the world's developing countries, where socioeconomic contrasts are
      often considerably greater. METHODS: In order to evaluate the extent of social
      differentials in mortality in a setting of major social inequality -- the State
      of Sao Paulo, Brazil, deaths in men aged 15-64 years residing in Sao Paulo from
      1980 to 1982 were linked in broad, occupationally-determined categories to
      estimates of population size based on the 1980 Brazilian national census. The
      occupational categorizations utilized a Brazilian classification scheme and
      additionally that of the British Registrar General. RESULTS: Mortality was 3.8
      and 2.9 times greater comparing least to most socially favoured occupational
      category in each of the two classification systems, respectively. Independent of
      system, mortality decreased approximately 1.1% for each 1% increase along the
      occupationally-defined social gradient. This decrease was 48% greater than the
      equivalent calculated decrease for men of England and Wales. CONCLUSIONS: These
      data support the contention that mortality for Brazilian adults, even more so
      than for adults of the world's more economically developed nations, is
      inextricably bound to the issue of social equity.

PMID- 7635594
TI  - The protective effect of a small amount of fish on coronary heart disease
      mortality in an elderly population.
AB  - BACKGROUND: A protective effect of a small amount of fish on coronary heart
      disease (CHD) mortality has been established in observational studies in middle
      aged people. In the present study this association was investigated in the
      elderly. METHODS: In 1971 CHD risk factors were measured in 272 people born
      before 1907. They belonged to a general practice in Rotterdam, the Netherlands
      and were followed for 17 years. The cross-check dietary history method was used
      to obtain information on fish consumption. RESULTS: During the follow-up period
      58 people died from CHD, 67 from cancer and 187 from all causes. In 1971 about
      60% of the elderly ate fish and 40% did not eat fish. Multivariate Cox
      proportional hazards analyses, taking the confounding effect of major risk
      factors into account, showed an inverse relation between fish consumption and 17
      year CHD mortality. The risk ratio (RR) for fish eaters compared with no-fish
      eaters was significantly different from unity (RR = 0.51, 95% CI: 0.29-0.89).
      Cancer and total mortality were not related to fish consumption. CONCLUSION: The
      results from the present study suggest that the protective effect of a small
      amount of fish in relation to CHD observed in middle-aged people seems also to be
      present in the elderly.

PMID- 7635596
TI  - Validity of urinary biomarkers of exposure to tobacco smoke following prolonged
      storage.
AB  - BACKGROUND: The utility of using biomarkers of smoking in epidemiological studies
      depends not only on the validity and precision of the laboratory procedure but
      often on the long-term stability of the analytes of interest in stored biological
      samples. METHODS: We retrieved urine samples collected in 1976-1977 from women
      included in a cohort study in Utrecht and for whom information on smoking status
      was available. Creatinine and thiocyanate were measured in 1976-1977 on fresh
      samples. Cotinine and creatinine were analysed in 1988 on urine stored at -20
      degrees C. RESULTS: Measurements of creatinine more than 10 years apart showed a
      correlation of 0.95 and equal means. Cotinine measurements made in 1988 allowed a
      clear separation of smokers and non-smokers (sensitivity 92%, specificity 100%),
      suggesting that concentrations retained their discriminant value even after 10
      years of storage. CONCLUSION: These results emphasize the possibilities offered
      by long-term storage, under proper conditions, of biological samples for
      subsequent determination of analytes which may emerge as the study progresses.

PMID- 7635599
TI  - Prevalence of senile dementia in Okinawa, Japan. COSEPO Group. Study Group of
      Epidemiology for Psychiatry in Okinawa.
AB  - METHODS. The prevalence of dementia was investigated in Okinawa Prefecture,
      Japan. In all, 3524 subjects, > or = 65 years old, were sampled randomly (urban
      and rural populations 61.1% and 38.9% respectively). Phase 1 of the survey was
      carried out by specially trained students of the Faculty of Medicine who used the
      Mini-Mental State (MMS) scale (interview rate: 94.3%) to screen 522 (15.8%) of
      the 3312 subjects for the phase 2 survey. Phase 2, conducted by psychiatrists
      using the Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R)
      criteria, detected 172 cases of dementia. RESULTS. The estimated prevalence of
      dementia was 6.7%. For women, the rate increased sharply in the 90-99 year old
      group, and was 41.4%; for men in the 90-99 year old group prevalence was 21.2%.
      The ratio of Alzheimer-type dementia to multi-infarct dementia was 1.5:1 (men
      1.2:1, women 1.7:1). The breakdown of the severity of dementia in the total cases
      was: mild 16.9%, moderate 30.8%, and severe 52.3%. The number of severe cases
      increased with age.

PMID- 7635598
TI  - Mortality in psychiatric patients, with a specific focus on cancer mortality
      associated with schizophrenia.
AB  - BACKGROUND: Higher mortality rates among psychiatric patients compared with the
      general population have been widely reported. On the other hand, lower cancer
      mortality for schizophrenics has been occasionally pointed out. Few studies from
      Japan have investigated mortality among psychiatric patients, and this study is
      the first large-scale follow-up in this country. METHODS: A total of 4980
      patients admitted to a national mental hospital from 1948 through 1982 were
      followed up until 31 August 1985. The standardized mortality ratios (SMR) were
      calculated in comparison to the general population, using the person-years
      method. RESULTS: The SMR for total deaths and those for malignancy were as
      follows for males/females respectively: 2.55/3.02 and 0.84/1.37 for
      schizophrenia, 1.76/2.37 and 1.44/2.10 for depression, 2.45/3.04 and 1.18/1.82
      for mania, 1.81/1.90 and 0.27/1.07 for neurosis, 5.55/4.33 and 1.85/3.34 for
      alcohol/drug abuse, and 3.65/3.57 and 1.01/0.72 for organic brain syndrome.
      CONCLUSIONS: The SMR for total deaths were significantly elevated in
      schizophrenia, depression, mania, neurosis, alcohol/drug abuse, and organic brain
      syndrome, respectively. The SMR for malignancy were not elevated nor lowered
      significantly in any of these disease categories. The SMR for stomach cancer in
      male schizophrenics was significantly lower (0.27; P < 0.05).

PMID- 7635600
TI  - Validity and repeatability of a modified Baecke questionnaire on physical
      activity.
AB  - BACKGROUND: In a pilot study for the European Prospective Investigation into
      Cancer and Nutrition (EPIC) a modification of the Baecke questionnaire on
      physical activity was tested for repeatability and relative validity in a
      population of 134 men and women aged 20-70 years. METHODS: For the assessment of
      repeatability Pearson's correlation coefficients and percentages of agreement
      after classification in tertiles were computed between administrations of the
      questionnaire at baseline, and after 5 and 11 months. Relative validity was
      determined by comparing the questionnaire to a four times repeated 3-day activity
      diary. RESULTS: Repeatability after 5 and 11 months was good, with test-retest
      correlation coefficients between 0.65 and 0.89 for main sections of the
      questionnaire. The percentages of agreement, exceeding chance (Cohen's kappa)
      were 57% and 56% for men (at 5 and 11 months respectively) and 41% and 46% for
      women. The correlations with the diaries were 0.56 in men and 0.44 in women.
      Agreement apart from chance between classification in tertiles for both methods
      was 35% for men and 10% for women. CONCLUSIONS: These data show that
      repeatability is good and relative validity as compared to an activity diary is
      moderate but well within the range of values found in other studies. The
      questionnaire is more valid in men than in women.

PMID- 7635601
TI  - Social desirability bias in dietary self-report may compromise the validity of
      dietary intake measures.
AB  - BACKGROUND: Self-report of dietary intake could be biased by social desirability
      or social approval thus affecting risk estimates in epidemiological studies.
      These constructs produce response set biases, which are evident when testing in
      domains characterized by easily recognizable correct or desirable responses.
      Given the social and psychological value ascribed to diet, assessment
      methodologies used most commonly in epidemiological studies are particularly
      vulnerable to these biases. METHODS: Social desirability and social approval
      biases were tested by comparing nutrient scores derived from multiple 24-hour
      diet recalls (24HR) on seven randomly assigned days with those from two 7-day
      diet recalls (7DDR) (similar in some respects to commonly used food frequency
      questionnaires), one administered at the beginning of the test period (pre) and
      one at the end (post). Statistical analysis included correlation and multiple
      linear regression. RESULTS: Cross-sectionally, no relationships between social
      approval score and the nutritional variables existed. Social desirability score
      was negatively correlated with most nutritional variables. In linear regression
      analysis, social desirability score produced a large downward bias in nutrient
      estimation in the 7DDR relative to the 24HR. For total energy, this bias equalled
      about 50 kcal/point on the social desirability scale or about 450 kcal over its
      interquartile range. The bias was approximately twice as large for women as for
      men and only about half as large in the post measures. Individuals having the
      highest 24HR-derived fat and total energy intake scores had the largest downward
      bias due to social desirability. CONCLUSIONS: We observed a large downward bias
      in reporting food intake related to social desirability score. These results are
      consistent with the theoretical constructs on which the hypothesis is based. The
      effect of social desirability bias is discussed in terms of its influence on
      epidemiological estimates of effect. Suggestions are made for future work aimed
      at improving dietary assessment methodologies and adjusting risk estimates for
      this bias.

PMID- 7635602
TI  - Serum retinol levels among preschool children in Central Java: demographic and
      socioeconomic determinants.
AB  - BACKGROUND: Vitamin A deficiency is a significant problem in many countries in
      the developing world. Reports have noted demographic and socioeconomic risk
      factors for vitamin A deficiency. 'Deficiency' has usually been defined by
      clinical signs and symptoms which represent only a small proportion of those
      children at increased risk for vitamin A preventable morbidity and mortality.
      METHODS: As part of a population-based trial of vitamin A to prevent childhood
      morbidity, we collected census data (n = 666), baseline socioeconomic data (n =
      636) and sera (n = 666) from children aged 6-48 months in 25 adjacent villages in
      a rural area in Central Java, Indonesia; there was more than 95% participation.
      We used t tests, ANOVA, and a multiple variable linear regression model in our
      analyses. RESULTS: Differences in mean retinol level were detected for the
      following variables: village (P < 0.001), child's age (P = 0.03), size of sibship
      (P < 0.001), mother's occupation (P < 0.01), mother's education (P = 0.05),
      father's education (P = 0.03), monthly household earnings (P = 0.02), land
      ownership (P = 0.03), possession of ducks (P = 0.06), radio or tape player (P =
      0.02), or a watch or clock (P = 0.07), and presence of a natural well (P = 0.09).
      Our regression model verified the predictive value of village, age, sibship, land
      ownership and earnings. CONCLUSIONS: We found that owning land and that the
      highest and lowest categories of reported household income were associated with
      higher serum retinol levels. We also noted clustering of serum retinol levels by
      village and discovered that children from larger sibships and infants had
      significantly lower serum retinol levels. Vitamin A supplementation of lactating
      mothers, particularly of high parity, and/or their infants should be considered.

PMID- 7635604
TI  - Mortality associated with multiple gestation in Malawi.
AB  - BACKGROUND: Multiple gestation is associated with increased maternal, perinatal,
      and infant mortality. The prevalence of multiple gestation varies widely with the
      highest rates reported among populations in Africa. There have been few
      population-based studies of the impact of multiple gestation on pregnancy
      outcomes in sub-Saharan Africa. METHODS: Data from a 1987-1990 prospective study
      of the effect of malaria chemoprophylaxis among pregnant women on birthweight and
      mortality of their infants in a rural area of Malawi were used to estimate the
      prevalence of multiple gestation and to quantify the risk of mortality associated
      with multiple gestation compared with single gestation. RESULTS: There were 88
      (2.2%) multiple gestations among 4049 women. Mortality was high; only 38% of
      mothers were known to have all their infants survive to 1 year, compared with 74%
      in singleton gestations. The increased mortality associated with multiple
      gestation was due to two factors: a higher frequency of low birthweight and a
      fourfold increase in perinatal mortality among the infants with birthweights > or
      = 2500 g and among infants with unknown birthweight. We estimated that multiple
      gestation contributes to 5.5% of the perinatal, 1.2% of the postperinatal, and
      11.5% of the maternal deaths in this population. CONCLUSION: Multiple gestation
      in Malawi contributed to increased perinatal and maternal mortality, but did not
      increase the risk of mortality after the perinatal period.

PMID- 7635603
TI  - Differential response to early nutrition supplementation: long-term effects on
      height at adolescence.
AB  - BACKGROUND: The classical risk approach to predicting who benefits from an
      intervention is unsound because it relies on the theoretical assumption that
      those at risk will necessarily benefit. A better approach to systematically test
      who benefits from nutrition supplementation is proposed using interactive models.
      METHODS: Differential effects of nutrition supplementation during early childhood
      on stature at adolescence were studied in 245 males and 215 females to identify
      determinants of long-term benefit from food supplementation. Factors studied
      included family socioeconomic status (SES) and children's home diet and diarrhoea
      during the first 3 years of life. To determine whether a factor conferred
      benefit, the statistical significance of the interaction between this factor and
      the intervention was tested. Data from the INCAP supplementation trial in
      Guatemala and from the follow-up of the same subjects at adolescence were used.
      RESULTS: Ordinary least squares (OLS) showed that high rates of diarrhoea in
      males and poor SES in females were significant determinants of benefit from
      supplementation at adolescence, and that the effects were mediated by length at 3
      years old. Results of two-stage least squares (2SLS) analysis showed that length
      at 36 months, maturation and maternal height were significant determinants of
      height at adolescence but SES was not. CONCLUSIONS: Nutrition supplementation in
      early childhood has long-lasting effects on body size and the larger benefits
      acquired by some groups of children remain throughout early adulthood. The
      relevance of these findings for screening and targeting of nutritional
      interventions is discussed.

PMID- 7635605
TI  - Increased risk of craniosynostosis with higher antenatal maternal altitude.
AB  - BACKGROUND: During the 1980s, the Colorado Department of Health received reports
      from several high-altitude communities of clusters of the malformation
      craniosynostosis. In a population-based, case-control study, we examined the
      association between overall and trimester-specific maternal antenatal altitude
      exposure and the occurrence of infant craniosynostosis. METHODS: We identified
      case children through a statewide registry and randomly sampled control children
      from birth records. By telephone interview, each mother provided data on the
      locations of all antenatal residences and places of employment as well as other
      factors. Staff mapped all locations and abstracted the corresponding altitudes.
      RESULTS: The odds ratio (OR) of any synostosis for a time-weighted mean antenatal
      altitude of > or = 2000 metres (high altitude) versus < 2000 metres (low
      altitude) was 1.4 (lower bound of the one-sided 95% test-based confidence
      interval (CI): 0.9). The OR was elevated in smokers but not in non-smokers. As
      compared to non-smokers, the OR of any synostosis for high-altitude smokers was
      4.6 (lower bound of the 95% one-sided exact CI: 1.7). Particularly elevated were
      the corresponding OR of coronal (18.1, 4.4) and metopic synostosis (16.3, 2.8),
      and OR for high-altitude exposure during the second trimester (any synostosis:
      6.4, 1.99; coronal: 28.6, 6.1; metopic: 26.7, 4.1). CONCLUSIONS: Antenatal
      maternal high-altitude exposure and smoking are associated with increased risk of
      infant craniosynostosis, perhaps through generation of intermittent hypoxaemia.

PMID- 7635606
TI  - Organic solvent exposure may increase the risk of glomerular nephropathies with
      chronic renal failure.
AB  - BACKGROUND: Several studies have suggested that exposure to organic solvents is
      associated with glomerular nephropathies (GN), but this relationship remains
      controversial. METHODS: A case-control study of 298 biopsy-proven cases and 298
      hospital controls, matched for year of birth, sex, origin, and place of
      residence, was conducted between 1989 and 1991 in five hospitals in the Paris
      area: 82 cases of membranous glomerulopathy were included; 100, nephrotic
      syndrome with either minimal change nephropathy or focal and segmental hyalinosis
      (MCN/FSH); and 116, IgA nephropathy (IgA N). Subjects were interviewed about
      their lifelong occupational and non-occupational activities. A 'blind' assessment
      of type, level, and duration of solvent exposure was carried out by two
      industrial hygienists. Human leucocyte antigen (HLA) phenotypes were determined.
      RESULTS: Among males, a clear association, which was not explained by social
      class, was observed between chronic renal failure and high exposure to solvents
      for both MCN/FSH (OR = 7.7, 95% CI: 1.4-41.6) and IgA N (OR = 3.5, 95% CI: 1.0
      11.8). The odds ratios increased with duration of exposure. No relationship was
      observed between such exposure and GN cases with normal renal function. No
      evidence was found that the HLA phenotype plays a role in the association between
      solvent exposure and the disease. CONCLUSIONS: These results support the
      hypothesis of a causal relationship between high solvent exposure, which
      concerned 15% of the males in this study, and the development of GN with chronic
      renal failure.

PMID- 7635607
TI  - Attitude of French general practitioners to the public health surveillance of
      communicable diseases.
AB  - BACKGROUND: The attitude of general practitioners (GPs) to public health
      surveillance is not well documented, even though they furnish essential
      information, in particular for sentinel surveillance among the general
      population. METHODS: The attitude of 560 French GPs to the surveillance of 17
      communicable diseases was researched. Half the GPs had previous experience in
      public health surveillance and the other half did not. Their motivation for
      belonging to a public health surveillance network and some of their demographic
      characteristics were also investigated. Their attitude was compared with an
      objective evaluation of public health surveillance priorities, based on 10
      criteria. RESULTS: Primarily, GPs are interested in the surveillance of uncommon
      and serious diseases (HIV infection, tuberculosis, meningitis), and/or
      preventable ones (viral hepatitis, flu' syndrome, measles, sexually transmitted
      diseases), which coincides with the choices made by public health decision
      makers. The age of the GPs, their type of practice (urban/rural), and their
      participation (or not) in a surveillance network modify their priorities: in
      general the GPs' perception of the risks to which their patients may be exposed
      influences their choice of which diseases should be subject to surveillance in
      general medicine.

PMID- 7635608
TI  - Estimation of the size of the HIV/AIDS epidemic due to blood transfusion in
      France.
AB  - BACKGROUND: This study presents estimates of the number of individuals
      contaminated by human immunodeficiency virus (HIV) via a blood transfusion
      received in France before the end of 1991 and those who have developed or will
      develop AIDS. METHODS: The computer simulation model takes into account several
      possible hypotheses concerning the annual number of infected blood donations
      collected before the introduction of HIV screening in August 1985, those
      collected between August 1985 and December 1991 not excluded by the testing
      procedure due to the seroconversion period, the number of labile blood components
      elaborated from one donation, the 5-year mortality rate of blood recipients, and
      the incubation delay. RESULTS: Results reproducing the evolution of the reported
      annual number of transfusion-associated AIDS cases were selected which enabled
      the estimation of the number of recipients infected (between 3300 and 4300) and
      of the number of transfusion-associated AIDS cases (between 1600 and 1800)
      compared with 1300 transfusion-associated AIDS cases reported by June 1993.
      CONCLUSION: This methodology could be used for other countries provided
      information required by the model is available.

PMID- 7635609
TI  - Model-based estimates of the risk of human immunodeficiency virus and hepatitis B
      virus transmission through unsafe injections.
AB  - BACKGROUND: Patient-to-patient transmission through contaminated medical
      equipment may be the principal route of nosocomial blood-borne infections
      globally. Quantifying cross infection risks could facilitate efforts to ensure
      safe injections in developing countries. METHOD: A mathematical model was
      developed to evaluate the risk of cross infection due to unsafe injections. The
      model was applied to immunization programmes with a fixed number of injections
      and in which unsterile needle and syringe reuse rates were specified. Risk
      estimates were generated using a range of human immunodeficiency virus (HIV) and
      hepatitis B (HBV) prevalences. RESULTS: The risk of cross infection is zero when
      properly sterilized equipment is used. With unsafe injections, the risk of cross
      infection with HBV is consistently higher than HIV for comparable levels of
      endemicity. A single reuse of each needle and syringe in areas with an HBeAg
      prevalence of 4% results in 980 cases of HBV/100,000 infants; reuse four times
      results in 3740 cases. When the HIV prevalence is 1% and the reuse rate is 4, 14
      to 35 cases of HIV/100,000 women could occur. Contamination of multidose vaccine
      vials could considerably increase these estimates. CONCLUSIONS: Neither HIV nor
      HBV transmission has been reported with injections administered through the
      Expanded Programme on Immunization. However, ample evidence exists that reuse of
      unsterile needles and syringes is common in developing countries. Ongoing efforts
      to ensure safe practices and improve injection technologies are required to
      protect these populations from both medical and traditional skin-piercing
      procedures.

PMID- 7635610
TI  - A rubella outbreak in the region of Rijeka, Croatia.
AB  - In the Region of Rijeka, Croatia, a combined vaccination programme against
      rubella has been carried out since 1976, so that children of both sexes are
      vaccinated at age 15 months and all girls at the age of 14 (8th grade of primary
      school). This vaccination programme has been carried out unchanged up till now.
      In 1989 a rubella epidemic arose in the Region of Rijeka (344,845 inhabitants).
      In all 2746 cases were reported, of which 79.1% were men, and the rest were women
      (20.9%). Among the reported cases in men, the majority (70.3%) were aged 15-19
      years. The number of reported cases was small and identical for both sexes under
      the age of 13, and above the age of 20 years. The number of men aged 15-19 who
      fell ill was considerably higher than the number of women of the same age. In
      this epidemic rubella remained a spring-time disease with its peak in April.

PMID- 7635611
TI  - Etiologic fraction analysis for continuously distributed outcome variables and
      empirical analogy with dichotomized outcome variables.
AB  - BACKGROUND: It is not clear from the published literature whether R2 estimated
      from linear regression models for continuously distributed outcome variables is
      analogous to the etiologic fraction for dichotomized outcome variables. This
      article attempts to address this issue. METHOD: Continuous and dichotomous
      outcomes of the same underlying attributes (gestational age and fetal growth)
      were compared using data from a recent study of birthweight distributions in
      ethnic Caucasian infants. RESULTS: The relative magnitudes of the etiologic
      fraction and R2 were quite similar for the same underlying attributes. For
      example, R2 and etiologic fraction for weight gain rate ranked 2 and 3,
      respectively, for fetal growth and ranked 4.5 and 5, respectively, for
      gestational duration. CONCLUSIONS: R2 estimated from linear regression models for
      continuously distributed outcome variables appears analogous to the etiologic
      fraction for dichotomized outcome variables. If due consideration is given to the
      underlying biological mechanisms of the studied attributes, R2 can be used as a
      measure of public health impact.

PMID- 7635612
TI  - Directive of the European Parliament and of the council on the protection of
      individuals with regard to the processing of personal data and on the free
      movement of such data. The International Epidemiological Association-IEA European
      Epidemiological Group.

PMID- 7635613
TI  - Odds ratios in cross-sectional studies.

PMID- 7635614
TI  - Odds ratio and relative risk for cross-sectional data.

PMID- 7635615
TI  - About self-assessment of neurological disability in multiple sclerosis.

PMID- 7635617
TI  - The effect of triclabendazole ("Fasinex") on protein synthesis by the liver
      fluke, Fasciola hepatica.
AB  - The effect of the active sulphoxide metabolite of the anthelmintic
      triclabendazole (TCBZ-SX, 15-50 micrograms ml-1) on the incorporation of
      radioactively labelled [14C] leucine by adult Fasciola hepatica tissue slices was
      measured by liquid scintillation counting. In addition, the ability of the
      microfilament-disrupting drug, cytochalasin B, and the microtubule-disrupting
      drug, tubulozole-C, to inhibit protein synthesis, was assessed by similar methods
      and compared with TCBZ-SX. The established protein synthesis inhibitors,
      cycloheximide and actinomycin D were used as positive controls. All the drugs
      showed a significant inhibition of protein synthesis, albeit to different
      extents; however, TCBZ-SX was the most potent, with no significant difference
      between its effect and that of cycloheximide or actinomycin D. Moreover, the
      concentration of TCBZ-SX, above 15 micrograms ml-1, had little further influence
      on incorporation of [14C] leucine. This investigation demonstrates the inhibitory
      effect of TCBZ-SX, cytochalasin B and tubulozole-C on protein synthesis in F.
      hepatica and confirms the qualitative observations made in several previous
      ultrastructural studies.

PMID- 7635616
TI  - Strongyloides stercoralis: histopathology of uncomplicated and hyperinfective
      strongyloidiasis in the Mongolian gerbil, a rodent model for human
      strongyloidiasis [corrected].
AB  - Tissues from corticosteroid-treated gerbils hyperinfected with Strongyloides
      stercoralis were compared grossly and microscopically to similar tissues from
      animals with uncomplicated strongyloidiasis. Gerbils with hyperinfection
      developed severe pulmonary alveolar haemorrhage with a variable degree of
      subacute eosinophilic interstitial pneumonia associated with numerous alveolar,
      vascular and interstitial larvae. Hyperinfection induced by corticosteroids,
      given either before inoculation of S. stercoralis larvae or after a chronic
      Strongyloides infection was established, produced similar lesions. In contrast,
      lungs from gerbils with uncomplicated Strongyloides infection had severe
      eosinophilic perivasculitis and vasculitis with very little haemorrhage, no
      pneumonia and no larvae. Sections of adult worms were present in the proximal
      part of the intestinal tract, lodged in spaces between mucosal epithelial cells.
      Adult worms were not associated with inflammation and were more common in the
      corticosteroid-treated gerbils. In corticosteroid-treated gerbils only, there
      were numerous larvae in the distal intestinal tract, throughout the intestinal
      wall and adjacent mesentery, within interstitial tissues and in lymphatic
      vessels. Significant inflammation with associated larvae was only present in the
      caecum and mesenteric lymph nodes, suggesting that the caecum was the main site
      for initiation of parenteral migration with subsequent invasion of the lymphatic
      system and lungs. The lesions in these gerbils were similar to those found in
      humans. Infection of gerbils with S. stercoralis is the best rodent model of
      human strongyloidiasis.

PMID- 7635618
TI  - Application of metabolic control analysis to the pathways of carbohydrate
      breakdown in Hymenolepis diminuta.
AB  - The application of metabolic control theory to carbohydrate breakdown in the
      tapeworm Hymenolepis diminuta shows that it is not necessary for both
      phosphoenolpyruvate carboxykinase and pyruvate kinase to be modulated in order to
      control the relative fluxes through the two arms of the phosphoenolpyruvate
      branchpoint. Changes in activity of enzymes outside of the two branches also
      influence the flux ratio. Control coefficients of individual enzymes for the
      fluxes through phosphoenolpyruvate carboxykinase and pyruvate kinase are not
      fixed, but vary as the flux ratio between the two arms of the branchpoint
      changes. The metabolic model can also be used to evaluate the role of the
      fructose-1,6-bisphosphate loop and to calculate metabolite transition time
      control coefficients.

PMID- 7635619
TI  - Phylogeny of the Polystomatidae (Platyhelminthes, Monogenea), with particular
      reference to Polystoma integerrimum.
AB  - Polystome phylogeny is examined, with emphasis on the dimorphism of the frog
      parasite Polystoma integerrimum, which exists in a fully differentiated and a
      neotenic form, and the evolutionary development of exclusively neotenic genera.
      Protopolystoma, which infects the aquatic toad Xenopus, has essentially the same
      morphology as the neotenic (branchial) adult of P. integerrimum and is
      interpreted as a neotenic genus; however, it inhabits the bladder of its host,
      the infection site of the normal adult of the dimorphic species. The sphyranurid
      Sphyranura, ectoparasitic on the external gills of the mud puppy Necturus,
      resembles the two-sucker larva of P. integerrimum in possessing a single pair of
      haptorial suckers in place of the 6 suckers of adult polystomes, and is probably
      a neotenic parasite associated with a neotenic host. The neotenic animals in
      general are parasites of aquatic hosts, and the uterus is lost or reduced in
      these genera; by contrast, uterine function is greatly enhanced among polystomes
      infecting amphibians best adapted to terrestrial life.

PMID- 7635620
TI  - Leishmania major: in vitro ultrastructural study of the paraxial rod of
      promastigotes.
AB  - The flagellum of Leishmania major promastigotes has an intraflagellar structure
      known as the paraxial rod (PAR) which extends from a point halfway in the
      flagellar pocket to the tip of the flagellum, lying opposite the axonemal
      microtubule doublets 4-7. An expansion of the axonemal plasma membrane envelops
      the PAR and may provide desmosomal attachment at the orifice of the flagellar
      pocket. The complex organization of the 4-6 nm thick filaments in the PAR was
      studied by us in cross, oblique, longitudinal and tangential sections by electron
      microscope. These filaments are disposed in two parallel lamellae, one alongside
      the axoneme (ca. 45 nm thick), and the other alongside the plasma membrane (ca.
      65 nm thick), with an interlamellar gap of about 22-28 nm. In each lamella, 8-12
      parallel series of longitudinal filaments at ca. 30 nm intervals interdigitate
      with coplanar parallel series of oblique filaments at ca. 25 nm intervals and
      inclined to the long axis of the flagellum at ca. 48 degrees, and ca. 55 degrees,
      in the inner (paraxonemal) and outer lamella, respectively. The parallel
      filaments in each of the longitudinal and oblique series are spaced at ca. 8 nm
      intervals. They are cross-striated at ca. 30 nm intervals by transverse filaments
      which terminate occasionally on adjacent axonemal microtubules 5 and 6 in the
      inner lamella, and the plasma membrane in the outer lamella. Extending across the
      interlamellar gap is a set of parallel rows of 7-12 nearly parallel filaments at
      ca. 20 nm intervals. The part of the flagellar plasma membrane enclosing the PAR
      has a subplasmalemmal cytoskeleton consisting of a layer of longitudinal 2 nm
      filaments at 8 nm intervals, obliquely striated by parallel 2 nm filament doubles
      at ca. (-65) degrees with the long axis of the flagellum and ca. 20 nm
      periodicity. Each filament doublet stria apparently gives origin to collinear
      short filament doublet extensions that curve into juxtaposed meshes of the outer
      lamella. Microtubules of the axonemal doublets 5 and 6 are connected to electron
      dense (ca. 12 nm thick) strips of the inner lamella of the PAR by longitudinal
      series of ca. 4 nm cross-links across a ca. 12 nm cleft.

PMID- 7635621
TI  - Meiosis and some aspects of cytological mechanisms of chromosomal sex
      determination in nematode species.
AB  - Meiotic division in Toxascaris leonina, Baylisascaris transfuga, Hexametra sp.,
      Toxocara canis, T. cati, Heterakis gallinarum and Physaloptera clausa of the
      class Nematoda were studied. Chromosomal sex determination type in different taxa
      is described. The XX-XO type of sex determination predominates in the species
      examined. A Y chromosome occurs only in B. transfuga. A correlation between the
      number and length of sex chromosomes and autosomes in the different taxa was
      established.

PMID- 7635622
TI  - Avermectin inhibition of larval development in Haemonchus contortus--effects of
      ivermectin resistance.
AB  - Avermectin (AVM) inhibition of the development of the free-living stages of
      Haemonchus contortus has been quantified in an assay in which nematode eggs are
      placed on an agar matrix containing serial dilutions of a drug in the wells of a
      microtitre plate. Development is allowed to proceed for 6 days by which time
      larvae in control wells (no drug) have reached the infective, third (L3) stage.
      At high concentrations (> 30 nM) ivermectin (IVM) paralyses L1 larvae soon after
      hatching, however, much lower concentrations (approximately 1 nM) are sufficient
      to inhibit development to the L3 stage which suggests that effects of the drug
      other than those relating to gross motor activity are responsible for the latter
      effect. The larval stages of IVM-susceptible H. contortus isolates from both
      Australia and South Africa, including isolates known to be resistant to
      levamisole or rafoxanide and/or the benzimidazoles, were equally sensitive to
      inhibition by AVMs. In contrast, 6 isolates of H. contortus resistant to IVM in
      vivo showed a reduced sensitivity to AVM inhibition of development. The order of
      potency of a limited range of AVMs as inhibitors of larval development was
      consistent with in vivo efficacy. Resistance ratios for IVM-resistant isolates
      were dependent on AVM structure, with AVM B2 the most sensitive probe for IVM
      resistance in the isolates tested.

PMID- 7635623
TI  - Kinetic disposition of xylene-based or aqueous formulations of deltamethrin
      applied to the dorsal mid-line of sheep and their effect on lice.
AB  - A xylene-based topical formulation of the synthetic pyrethroid insecticide
      deltamethrin was applied to the dorsal mid-line of 2 groups of 5 Merino sheep
      within 24 h after shearing. One group was free of ectoparasites and the second
      was infested with sheep body lice, Bovicola (Damalinia) ovis. A water-based
      deltamethrin formulation was applied to the dorsal mid-line of a third group of 5
      Merinos which were infested with lice. Insecticide concentrations on the wool of
      the back, upper and lower body and in the skin and bloodstream were measured at
      regular intervals between 1 and 98 days after treatment. Movement of the
      deltamethrin from the back to the lower body occurred within 24 h on all 3
      groups, but maximum concentrations took 4-5 days to develop on the fleece in
      sheep treated with the xylene-based formulation and 11 days in sheep treated with
      the water-based formulation. There was a significant difference in concentration
      of deltamethrin close to the dorsal mid-line between the groups treated with the
      different formulations. Overall, concentrations of deltamethrin were lower at all
      sites examined on the sheep treated with the water-based formulation. Levels of
      deltamethrin in the tip of the fleece were significantly greater than those in
      the base and there was little movement of deltamethrin down the staple. The
      concentration of deltamethrin in the skin was significantly lower than the
      concentration in the wool and fell below the amount required to kill lice fully
      susceptible to deltamethrin after 12 days. Deltamethrin levels in the blood were
      near the limits of detection in all groups at all observations, indicating that
      there was little absorption or re-distribution of deltamethrin via the
      bloodstream. Most lice were killed after 20 h of exposure in vitro, to wool
      samples collected between 1 and 14 days after treatment. However, many lice
      survived in samples containing the same concentration of deltamethrin, but
      collected between 16 and 98 days after treatment. Numbers of lice surviving
      increased with the sampling time after treatment, suggesting that the bio
      availability of the deltamethrin changed as the insecticide aged in the fleece.

PMID- 7635624
TI  - Differentiation of Haemonchus placei from H. contortus (Nematoda:
      Trichostrongylidae) by the ribosomal DNA second internal transcribed spacer.
AB  - There has been much debate as to whether H. placei is a separate species to H.
      contortus. The aim of this study is to provide molecular information to assess
      the species status of H. placei. Using the polymerase chain reaction, the second
      internal transcribed spacer (ITS-2) of ribosomal DNA was amplified and sequenced.
      Comparison of the 231 base pair ITS-2 sequences showed no intraspecific variation
      in H. contortus, among one isolate from each of the United Kingdom. Switzerland
      and China and 5 isolates from within Australia, or among 3 Australian isolates of
      H. placei. Three (1.3%) nucleotide differences were detected between the ITS-2
      sequences of H. contortus and H. placei. In addition, 2 diagnostic sites for the
      endonucleases BfaI and FokI allowed the delineation of H. placei from H.
      contortus. The data presented herein support previous morphological and genetic
      evidence that H. placei is a separate species to H. contortus.

PMID- 7635625
TI  - The epidemiology of helminth infections of growing sheep in Argentina's western
      pampas.
AB  - Seasonal population trends of helminth parasites of growing lambs were
      investigated over 4 years. Successive worm-free lambs were grazed together with
      untreated lambs for 20-30 days and then slaughtered for helminth counts 2 weeks
      after their removal from pasture. Likewise untreated lambs from the same flock
      were slaughtered from 2 to 15 months of age for worm counts in the same way as
      tracer lambs. The predominant parasites were Haemonchus, Nematodirus and
      Trichostrongylus. Haemonchus contortus was found to be of major importance and
      the flock acquired massive worm burdens from summer to mid-autumn. Minimum
      burdens were seen from winter to early spring and maximum L4 stages were found
      from mid-autumn to early winter. Nematodirus burdens increased from December with
      a peak in late summer and then decreased to low values. Maximum larval
      availability was in autumn to early winter. Trichostrongylus (mainly T.
      colubriformis) populations increased in autumn and peaked in June-July, while the
      highest larval availability was in autumn. The minor genera recovered were
      Ostertagia, Cooperia, Trichuris, Oesophagostomum and Moniezia. Dictyocaulus,
      Chabertia and Teladorsagia were noted occasionally and liver flukes were not
      detected. No important and pathogenic numbers of L4 stages were seen and all
      predominant species were able to survive over summer or winter in pasture.

PMID- 7635626
TI  - Interaction between Ostertagia circumcincta and Haemonchus contortus infection in
      young lambs.
AB  - Twenty-one-week-old, worm-free, pen-reared lambs were infected with either 6000
      O. circumcincta L3 per week, or 3000 H. contortus L3 per week, or both (9000 L3
      per week). Egg counts were monitored throughout the experiment, and worm burdens
      and larval establishment rates of both worm species were estimated after 4, 7, 10
      and 13 weeks of infection. After 10-13 weeks of infection with H. contortus only,
      establishment of O. circumcincta was lower than in previously uninfected
      controls, demonstrating that a high level of immunity to H. contortus affords
      some cross-protection against O. circumcincta. Total H. contortus worm burdens
      and egg counts (about 2000 worms and 3000 e.p.g., respectively) in sheep infected
      with both worm species were less than half those observed in sheep infected with
      H. contortus alone (about 5000 worms and 10,000 e.p.g., respectively). Cross
      protection between the two species was observed, but was probably less important
      than the reduction in H. contortus establishment that was caused by O.
      circumcincta disrupting abomasal physiology.

PMID- 7635627
TI  - Protection against multiply drug-resistant and geographically distant strains of
      Haemonchus contortus by vaccination with H11, a gut membrane-derived protective
      antigen.
AB  - H11 is a "hidden antigen" derived from adult Haemonchus contortus which is
      capable of conferring a high degree of protection against subsequent challenge.
      To be commercially useful, any vaccine based on this antigen must protect against
      field strains and drug-resistant worms. The results show that vaccination with
      H11 affords high levels of protection against the multiply drug-resistant (MDR)
      Lawes strain of Haemonchus contortus. Moreover, there was no difference in
      protection whether the H11 was extracted from drug-resistant or susceptible
      worms, indicating that multiple drug-resistance does not significantly alter the
      immunogenicity of H11. Ideally, a commercial vaccine based on this antigen should
      also be capable of protecting against strains from geographically separate areas,
      so that it is not necessary to manufacture "region-specific" vaccines.
      Vaccination with H11 purified from either Australian or U.K. Haemonchus contortus
      was effective in protecting against subsequent challenge with Australian larvae,
      indicating that one type of H11 should have world-wide application.

PMID- 7635628
TI  - The immune responsiveness of Romney sheep selected for resistance or
      susceptibility to gastrointestinal nematodes: lymphocyte blastogenic activity,
      eosinophilia and total white blood cell counts.
AB  - Blastogenic activity, eosinophil and total white blood cell counts (TWBC) were
      examined over a period of 14 weeks in Romney lambs, genetically resistant or
      susceptible to gastrointestinal nematodes. The lambs were infected with 5000
      infective Trichostrongylus colubriformis larvae twice weekly. Compared to
      preinfection levels, the blastogenic activity of unstimulated lymphocytes in
      lambs of both lines peaked at week 3, and was significantly higher in resistant
      than in susceptible lambs. These changes may have been due to in vivo polyclonal
      activation. Lymphocytes from susceptible sheep responded more strongly to Con A,
      PHA and PWM than cells from resistant sheep. Counts per minute (c.p.m) for Con A-
      and PHA-stimulated lymphocytes increased in both lines of sheep from week 2 to
      week 7 and then returned to initial levels. An increase in c.p.m. in PWM
      stimulated cell cultures was observed from weeks 3 to 5 in both groups. The
      blastogenic activity for LPS-stimulated cultures was significantly higher for
      resistant than susceptible sheep at weeks 3 and 4. No significant correlations
      between the decline in faecal egg counts (FEC) and the blastogenic activity was
      observed. Eosinophil counts in peripheral blood began to increase one week
      earlier in resistant than in susceptible sheep. No significant correlation
      between FEC and eosinophil counts was observed in resistant lambs, whereas in
      susceptible lambs a significant correlation was found between FEC and eosinophil
      counts at some sampling times. TWBC in resistant lambs steadily increased with
      infections whereas susceptible lambs showed a decrease until week 5 and then
      steadily increased. There was no significant correlation between the decline in
      FEC and TWBC.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7635629
TI  - Increased antimalarial activity of azithromycin during prolonged exposure of
      Plasmodium falciparum in vitro.
AB  - The minimum inhibitory concentration, MIC, of azithromycin was determined for 2
      isolates of Plasmodium falciparum at 48 and 96 h. The MIC at 48 h for the K1 and
      FC isolates were 6.2 and 8.7 micrograms/ml, respectively. At 96 h, the MIC
      decreased to 0.08 microgram/ml for the K1 isolate and 0.04 microgram/ml for the
      FC isolate. The marked reduction in the MIC values between the first and second
      asexual erythrocytic cycles suggests that the drug acts slowly and that it may
      have to be used in combination with a faster acting drug.

PMID- 7635630
TI  - Murine strongyloidiasis: the effects of cyclosporin A and thiabendazole
      administered singly and in combination.
AB  - A single Cyclosporin A (CsA) dose of 30 mg kg-1 given orally at day 4 post
      infection (p.i.) to Sprague-Dawley rats infected with Strongyloides ratti,
      reduced the faecal larval count by 46.8 +/- 1.2%. CsA was equally effective when
      the same dose rate was administered subcutaneously at day 4 p.i., reducing the
      faecal larval count by 41.6 +/- 8.6%. Thiabendazole (TBZ) given orally at 5 or 10
      mg kg-1 (single dose at day 4 p.i.) reduced the faecal larval counts by 57.1 +/-
      4.1% and 69.0 +/- 9.6%, respectively. Orally administered CsA was less effective
      than 5 mg TBZ kg-1 (at day 4 p.i.) Co-administration of 5 mg TBZ kg-1 and CsA did
      not elicit synergy or additive efficacy, indicating that CsA did not antagonise
      the anti-strongyloides activity of TBZ. The data suggests that for patients with
      current, historical or serological evidence of strongyloidiasis, CsA may be used
      where immunosuppressive therapy is required for other concurrent reasons or when
      TBZ is contraindicated.

PMID- 7635631
TI  - A simple method for collecting eggs of taeniid cestodes from fresh, frozen or
      ethanol-fixed segments.
AB  - A simple method was devised for collecting eggs of Taenia taeniaeformis and T.
      saginata. All gravid segments, either fresh or frozen or 70% ethanol-fixed, were
      gently scraped using a pestle on a 150 mesh stainless steel sieve. Eggs and
      tissue debris were washed out all together with mouse tonicity phosphate buffered
      saline (MTPBS) through the 150 mesh sieve into a glass beaker. Egg suspension
      with a huge amount of tissue debris in MTPBS was centrifuged 5 min at 3000 r.p.m.
      (x 1600 g) and the pellet of eggs and tissue debris was resuspended with 1 vol.
      of MTPBS and 2 vol. of Percoll (Pharmacia) and centrifuged 60 min at 3000 r.p.m.
      More than 90% of eggs sedimented in the pellet. The supernatant covered with
      tissue debris was decanted, and the egg pellet was resuspended and centrifuged
      several times with MTPBS to remove Percoll. It is suggested that this simple
      method may prove useful for preparation of eggs of biohazardous taeniid cestodes,
      such as Taenia solium and Echinococcus spp.

PMID- 7635632
TI  - [3H]-amino acid uptake and metabolic studies on Gigantocotyle explanatum and
      Gastrothylax crumenifer (Digenea: Paramphistomidae).
AB  - The amphistomes Gigantocotyle explanatum and Gastrothylax crumenifer utilize
      leucine, alanine, proline and methionine during in vitro incubations.
      Autoradiography on sections of these flukes reveal a time-dependent differential
      incorporation of tritium-labelled amino acids in various tissues. The tegument
      appears to be the primary surface through which amino acids are absorbed.
      Following absorption, the reappearance of [3H]-leucine and [3H]-alanine on the
      tegumental surface during late chase periods indicates their possible involvement
      in tegumental secretion. A combination of diffusion and carrier-mediated uptake,
      possibly involving gamma-glutamyl transpeptidase, is indicated. The transport
      loci show differences in carrier-affinity (Kt) and maximum uptake velocities
      (Vmax) for amino acids under study, which suggest multiple transport molecules.
      Metabolic studies reveal that aspartate, alanine, ornithine, proline, leucine and
      methionine undergo transamination through 2-oxoglutarate-linked transaminases,
      distributed in the cytosolic and mitochondrial fractions of G. explanatum and G.
      crumenifer. With the exception of alanine transaminase, the enzyme levels in the
      cytosolic fraction were higher than the mitochondrial fraction of the two
      amphistomes. Predominantly cytosolic glutamate dehydrogenase which was
      comparatively higher in G. explanatum, catalyse amination of alpha-ketoglutarate.
      A high level of cytosolic arginase alone does not indicate a functional urea
      cycle. A tentative pathway of amino acid metabolism in these amphistomes is
      proposed.

PMID- 7635633
TI  - Schistosoma mansoni and S. haematobium: miracidial host-finding behaviour is
      stimulated by macromolecules.
AB  - The miracidia of Schistosoma mansoni and S. haematobium approach their host
      snails by increasing their rate of change of direction (RCD) in increasing
      gradients of snail-conditioned water (SCW), and they perform a turnback response
      in decreasing gradients. After contact with the host "repeated investigation" is
      the typical host-specific response. Both species show no significant directed
      chemotactical orientation towards their snail hosts. All three host-finding
      responses (increased RCD, turnback response, and "repeated investigation") seem
      to be stimulated in both species by a similar component of SCW, a macromolecular
      glycoconjugate with a molecular weight > 30,000. The saccharide chains seem to be
      O-glycosidically linked via serine and N-acetylgalactosamine. The glycoconjugate
      is sensitive to lysozyme which may suggest that muramic acid as a gastropod
      specific component is involved in the recognition process. Small molecular
      components of SCW, as well as magnesium chloride offered as pure chemical, may
      cause a moderate increase in the RCD. Therefore a minor contribution of these
      components to the host-finding response of schistosome miracidia cannot be
      excluded. That schistosome miracidia respond to complex macromolecules as host
      cues may indicate an adaptation to avoid interference of the host-finding with
      ubiquitous small molecular mud components and it might enable the miracidia to
      achieve a high degree of host-specificity in their host-finding.

PMID- 7635634
TI  - Analysis of proteins related to conditioning for arrested development and
      differentiation in Haemonchus contortus by two-dimensional gel electrophoresis.
AB  - The abundance of the majority of proteins of infectious third-stage larvae (L3)
      of Haemonchus contortus, conditioned for arrested development, remained
      unaltered. Only seven proteins showed quantitative differences as observed by two
      dimensional gel electrophoresis. These differences were also observed in a
      laboratory strain which has lost the ability for arrested development. The
      abundance of two of these proteins increased dramatically during conditioning of
      larvae for 5-10 weeks. This coincided with the highest percentage of inhibited
      larvae in experimental infections. Moreover, the abundance of these proteins
      decreased again after prolonged conditioning (22 weeks). The abundance of the
      other 5 proteins was not correlated to the percentage of inhibition. We therefore
      conclude that these proteins are involved in the aging process of larvae. The
      changes in protein between free-living (L3) and parasitic stages (L4) were large
      and seem to reflect the large environmental changes experienced by the larvae
      when entering a mammalian host. Early fourth- (EL4) and late fourth- (LL4) stage
      larvae differed in 9 proteins. One protein was stage-specific for EL4. These
      results imply that only minor alterations do occur in these stages
      notwithstanding the large morphological differences between these larvae.

PMID- 7635635
TI  - Re-examination of spermatogenesis of Multicotyle purvisi (Platyhelminthes,
      Aspidogastrea).
AB  - Examination of spermatogenesis in Multicotyle purvisi revealed that the process
      follows the classical pattern previously described for many parasitic
      platyhelminths, especially other Aspidogastrea and Digenea. Free flagella (with
      an intercentriolar body between the basal bodies and with striated flagellar
      rootlets) and a median cytoplasmic process grow from a zone of differentiation.
      The flagella then fuse with the process in a proximo-distal direction and nucleus
      and mitochondrion grow out into the elongating spermatid. Spermatids are pinched
      off at the base, and rootlets and intercentriolar body remain behind in the
      residual cytoplasm. It is suggested that the aberrant processes described in an
      earlier report constitute a pathological condition or a response to stress.
      Changes in the intercentriolar body during spermiogenesis are documented and for
      the first time in a platyhelminth it is demonstrated that rootlets and
      intercentriolar bodies are discarded and left behind in the residual cytoplasm.

PMID- 7635636
TI  - Evaluation by larval recovery of mebendazole activity in experimental murine
      toxocariasis.
AB  - We have studied the action of mebendazole on experimental murine toxocariasis
      using different formulations and vehicles. The treatment efficacy was evaluated
      by larval recovery after digesting several tissues. In the first part of the
      experiment, the drugs were administered on days 1-3 post infection (p.i.)
      inclusive (hepato-pulmonary phase of the migration), then the animals were
      sacrificed by the 1st week p.i. In the second part of the experimental protocol,
      the treatments were administered on days 4-6 p.i. inclusive (myotropic
      neurotropic phase of the migration), with sacrifice of the animals by the 7th
      week p.i. The 2nd pattern of treatment reduced more effectively the total larval
      recoveries compared with control animals. However, the larval distribution by
      organs was scarcely affected. The first pattern of treatment reduced less
      effectively the total number of larvae, but it significantly inhibited migration.

PMID- 7635637
TI  - In vitro drug susceptibility of 29 isolates of Giardia duodenalis from humans as
      assessed by an adhesion assay.
AB  - Twelve isolates of Giardia duodenalis from Caucasian hosts in the Perth
      metropolitan area, along with 16 isolates from Aborigines in the north of Western
      Australia and the reference isolate P1C10 were examined for their in vitro drug
      sensitivity. Dose-response curves were constructed for each isolate for
      metronidazole, the most common clinically used antigiardial agent, as well as for
      the benzimidazole compound albendazole. Less than a 9-fold variation was found in
      the susceptibility of the isolates to albendazole, while for metronidazole there
      was well over a 16,000-fold variation between the same group of isolates. In
      addition, it was found that isolates of Giardia obtained from Aboriginal hosts
      were significantly less sensitive to albendazole than those obtained from
      Caucasians. The results of this study have important implications for the
      continued use of metronidazole and the potential use of albendazole for the
      treatment of giardiasis.

PMID- 7635638
TI  - A repetitive DNA probe for the sensitive detection of Fasciola hepatica infected
      snails.
AB  - Epizootiologic studies on F. hepatica frequently use microscopic techniques for
      the detection of infected snails, however, the poor efficiency, sensitivity, and
      specificity associated with these techniques limit their usefulness. A DNA-based
      test for the identification of snails infected with larval stages of F. hepatica
      would solve these problems and enable a level of detection accuracy previously
      unavailable. We have cloned and sequenced a 124 bp fragment of repetitive DNA
      from F. hepatica which hybridizes specifically with DNA of F. hepatica but not
      with DNA of its snail intermediate hosts Fossaria cubensis and Pseudosuccinea
      columella, or with DNA of Fascioloides magna and Paramphistomum liorchis,
      ruminant trematodes which share the same intermediate host and same enzootic
      range as F. hepatica. Using this 124 bp fragment as a probe, infection in snails
      was detected immediately following miracidial penetration, thus a sensitivity
      equivalent to the minimum biologic unit of the parasite was achieved. This 124 bp
      repeated sequence belongs to a large family of 124 bp repeats that share a high
      level of sequence identity and constitute approximately 15% of the F. hepatica
      genome. We also report here the development of a quick and inexpensive DNA
      extraction protocol for use in field-collected snails. Thus, we have developed
      both a highly sensitive and specific DNA probe and a means to use the probe in a
      large epizootiologic study of F. hepatica where thousands of field-collected
      snails need to be assayed for infection.

PMID- 7635640
TI  - Antibody degradation in wound exudates from blowfly infections on sheep.
AB  - Sheep were immunised with ovalbumin and then infected with the sheep blowfly,
      Lucilia cuprina in order to study immunoglobulin and specific antibody
      degradation at the wound site. Serum and wound exudates were collected over the
      infection period and the dry weight and protein content of the exudates were
      determined. Exudates were analysed by SDS-PAGE and immunoblotting for IgG
      degradation. Levels of IgG and specific anti-ovalbumin antibodies in the exudates
      were measured by ELISA. The total weight of exudates increased over the whole
      period of the infection, while protein content increased in the first 24 h and
      then remained relatively constant. Immunoglobulin was present 6 h after infection
      and levels increased with protein content. However, the levels of IgG measured
      were quite different depending on the secondary antibody used in the ELISA. A
      monoclonal antibody measured mainly intact IgG while a polyclonal anti-IgG
      measured intact and degraded IgG. This allowed an estimation that approximately
      60% of the IgG in exudates was degraded from 6 h after infection. Assays in vitro
      showed that L. cuprina larval enzymes degraded sheep antibody. However,
      measurement of specific anti-ovalbumin levels in exudates suggested that although
      high levels of antibody were degraded this did not necessarily decrease the level
      of antigen binding. As a result, IgG degradation may assist and not hinder
      vaccine development by allowing antibody fragments to penetrate the peritrophic
      membrane and access gut cell antigens.

PMID- 7635639
TI  - Cloning of an early immunodominant filarial antigen: a member of the Brugia
      malayi myosin heavy chain gene family.
AB  - Partial protective immunity to filariasis can be achieved in animals by
      vaccination with irradiated infective larvae. A Brugia malayi cDNA expression
      library was screened with serum pools from vaccinated and infected jirds to
      select clones that expressed potentially protective recombinant antigens that
      were preferentially recognized by sera from vaccinated animals. Bmmyo-2, the
      largest of a group of related clones, was studied in detail. Jirds produced
      strong antibody responses to the protein product of Bmmyo-2, Bmmhc-B, as early as
      1 month after vaccination with irradiated larvae. Antibody responses to Bmmhc-B
      in infected jirds were weaker than those of vaccinated jirds, and they developed
      somewhat later. Antibodies produced to Bmmhc-B were reactive with a 200 kDa
      native B. malayi antigen by immunoblot and with muscle bands in the body wall of
      microfilarial by indirect immunofluorescence. Sequence analysis of the 1454 bp
      cDNA insert of Bmmyo-2 showed that it codes for a portion of the rod region of a
      B. malayi myosin heavy chain isoform. The deduced amino acid sequence of Bmmyo-2
      is 74.6% identical with that of the corresponding region of Caenorhabditis
      elegans myosin heavy chain B, but only 64.6% identical with a recently described
      B. malayi myosin heavy chain, Bmmhc-A.

PMID- 7635642
TI  - Toxoplasma gondii: reactivity of murine sera against tachyzoite and cyst antigens
      via FAST-ELISA.
AB  - The murine serological response to Toxoplasma gondii tachyzoite and cyst antigens
      was determined using FAST-ELISA. The serum IgG response to tachyzoite antigen was
      much stronger than that to cyst antigen. Adsorption of immune sera with
      tachyzoite antigen sharply reduced the reactivity in ELISA with tachyzoite
      antigen, but had no effect on the titre against cyst antigen, implying that there
      is virtually no antigenic overlap between the 2 stages. In sequential sera from
      infected mice the IgG antibody response against tachyzoites was always higher
      than the response to cyst antigen, whereas the IgM response to cysts was always
      higher than that to tachyzoites and remained detectable for at least 11 months.

PMID- 7635641
TI  - Variation in immune responsiveness of sheep to the antigens of intestinal
      nematodes and blowfly larvae.
AB  - The total and IgG1 antibody responses to the intestinal nematode parasites
      Haemonchus contortus and Trichostrongylus colubriformis were measured in the
      serum of 160 lambs, 4 months of age. These antibodies had developed as the result
      of natural exposure to the parasites on pasture. Three sires were examined and
      strong sire effects on half-sib progeny were found. Plotting of ELISA antibody
      results in two dimensions revealed clustering of responses within sire groups.
      Bimodal antibody distributions were also observed within sire groups and the
      whole population for T. colubriformis. A bimodal distribution of antibodies to H.
      contortus was found for one sire group but not for the whole population. The
      injection of blowfly larvae (Lucilia cuprina) extract into 42/160 lambs at a
      later age (12 months) was followed by increased antibodies to L. cuprina and an
      apparent increase in antibodies to T. colubriformis. A bimodal distribution for
      antibodies to L. cuprina was found in one sire group and in the whole population.
      These bimodal distributions of antibodies to L. cuprina did not coincide with the
      distribution of antibodies to T. colubriformis or H. contortus, measured on the
      same serum samples. It was concluded that high and low responder sire groups
      could be differentiated in lamb populations for all three parasites. These
      effects persisted during lamb maturation and appeared to be genetic effects.
      Finally, cross-reacting antibodies between L. cuprina and T. colubriformis appear
      to be stimulated by injection of L. cuprina antigens.

PMID- 7635643
TI  - Differential expression of glutathione S-transferase (GST) by adult
      Heligmosomoides polygyrus during primary infection in fast and slow responding
      hosts.
AB  - Glutathione S-transferase (GST) specific enzymatic activity, assayed with the
      model substrate 1-chloro-2,4-dinitrobenzene, was 45% higher in adult
      Heligmosomoides polygyrus passaged through a slow responder mouse strain,
      C57/BL10 compared to worms passaged through a fast-responder strain (SWR x SJL)
      F1. Western analysis using polyclonal antisera raised to purified H. polygyrus
      GSTs did not appear to positively correlate the expression of GST protein with
      functional enzymatic activity. However, western blotting did indicate a sex
      linked expression pattern of GST protein, with male worms expressing a higher
      ratio of the 24 kDa to the 23 kDa GST family than female worms.

PMID- 7635644
TI  - Differences in a ribosomal DNA sequence of morphologically indistinguishable
      species within the Hypodontus macropi complex (Nematoda: Strongyloidea).
AB  - The nucleotide sequence of the second internal transcribed spacer (ITS-2) from
      ribosomal DNA has been determined for 3 members of the Hypodontus macropi species
      complex. Sequences were compared from nematodes collected from 3 species of
      Australian macropodid marsupial, Petrogale persephone, Macropus robustus robustus
      and Thylogale billardierii. The ITS-2 of each operational taxonomic unit ranged
      from 287 to 292 bases in length, and had a GC content of 36.6-40.1%. Differences
      in nucleotide sequence between nematodes from the different host species ranged
      from 25.0% to 28.3%. The data suggest that H. macropi from P. persephone
      represents a different species to those in M. r. robustus and T. billardierii.
      The unique feature of this study is that it represents a comparison of the
      ribosomal DNA sequences of nematode species which are morphologically
      indistinguishable but which have been demonstrated to be genetically distinct
      (i.e. cryptic) species based on electrophoretic data. The results also
      demonstrate further that morphological characters alone are often not adequate
      for species recognition. Differences between these 3 species of H. macropi in
      their recognition sites for restriction endonucleases, indicates that a PCR-RFLP
      approach could be used, in conjunction with allozyme electrophoresis, to
      establish how many species are present within the H. macropi complex.

PMID- 7635645
TI  - Effects of Echinostoma caproni infection on the neutral lipid content of the
      intestinal mucosa of ICR mice.
AB  - Thin-layer chromatography was used to examine the effects of adult Echinostoma
      caproni infection on the intestinal mucosa of ICR mice. At 2 weeks postinfection
      the mucosa of infected mice showed a marked elevation of the free fatty acid
      fraction compared to that of the uninfected controls. The most abundant neutral
      lipid fraction of the adult worms was free sterol.

PMID- 7635646
TI  - Effect of superoxide dismutase and 21-aminosteroids (lazaroids) on microvascular
      perfusion following ischemia-reperfusion in skeletal muscle.
AB  - Intravital video microscopy was used to test superoxide dismutase and a lazaroid
      analogue, U-74389F, as a pretreatment for ischemia-reperfusion-induced
      microvascular dysfunction in skeletal muscle. Twenty-two male Wistar rats (350
      400 g), anesthetized with sodium pentobarbital (65 mg/kg i.p.), were divided into
      groups to test the lazaroid analogue U-74389F (3 mg/kg; n = 8), a citric
      acid/citrate mixture (CS-4; n = 4) used as the vehicle for the lazaroid analogue,
      superoxide dismutase (SOD, 10 mg/kg; n = 5), and saline (n = 5). Normothermic
      ischemia of the extensor digitorum longus muscle was induced for 3 h by
      tightening a tourniquet placed around the limb above the muscle. Measurements of
      the number of perfused capillaries (CDper; mm-1) and capillary red blood cell
      velocity (VRBC; mm/s) were made after 30, 60 and 90 min of reperfusion. Thirty
      minutes following release of the tourniquet, all test groups showed a significant
      drop in CDper. The extent of this reduction was maximal in SOD treated muscles,
      while it was minimized in the lazaroid-treated muscles following 90 min
      reperfusion. Hyperemia occurred only in muscles treated with saline or lazaroid.
      The hyperemia was of limited duration in saline-treated muscles, but lasted the
      entire reperfusion period following lazaroid treatment. An index of microvascular
      flow, estimated from the product of VRBC and CDper, indicated that flow was
      significantly greater in muscles treated with lazaroids as compared with all
      other groups following the 90-min reperfusion. We conclude that whereas SOD was
      detrimental, the lazaroid analogue U-74389F improved microvascular perfusion
      following 3 h of no-flow ischemia and 90 min reperfusion.

PMID- 7635647
TI  - Effects of percutaneous transluminal angioplasty on skin microcirculation in
      patients with disabling peripheral arterial occlusive disease.
AB  - Percutaneous transluminal angioplasty (PTA) provokes a huge trauma to the
      arterial wall and potentially liberates fragments of atherosclerotic material
      that may impair the microcirculation downstream. Incidence and clinical relevance
      of such embolisms are not known. This study was aimed at investigating the
      changes of the skin microcirculation in patients with peripheral arterial
      occlusive disease undergoing PTA of the lower limbs. Pedal transcutaneous oxygen
      tension (tcpO2) and nailfold skin microcirculation were measured in 21 patients
      with disabling peripheral arterial occlusive disease before and after PTA.
      Sixteen matched patients undergoing arteriography alone were used as controls.
      The skin microcirculation was investigated at the nailfold of the great toe by
      the combination of laser Doppler fluxmetry and dynamic capillaroscopy. PTA was
      successful in all patients. The tcpO2 decreased immediately after PTA (delta
      tcpO2 = -5 mm Hg; p < 0.004), whereas it tended to increase (delta tcpO2 = 1 mm
      Hg; NS) following arteriography as compared with baseline values. By contrast,
      blood flow increased in both groups, predominantly for the total circulation in
      the PTA group and for nutritional circulation (p < 0.0017) in the arteriography
      group, respectively. Consequently, the 'nutritional index', i.e., the index of
      nutritional versus total microcirculation, was decreased following PTA,
      particularly following mechanical recanalization (p < 0.02), but did not change
      in the controls. The changes of this 'nutritional index' and those of the tcpO2
      were positively correlated (r = 0.4, p = 0.023).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7635648
TI  - Skin microcirculation in patients with sequelae from local cold injuries.
AB  - The microcirculation in the skin was assessed in 31 patients with sequelae from
      local cold injuries (LCI) in the extremities. All patients reported cold
      intolerance 3-4 years after the primary cold injury, which they sustained during
      military service. The used methods were laser Doppler fluxmetry, transcutaneous
      oxygen tension (TCpO2) and vital capillaroscopy. Neurovascular reflexes were
      stimulated by deep inspiration, digital cuff occlusion of venous and arterial
      circulation, neck cooling with an ice bag and water immersion at 5 and 15 degrees
      C. Unaffected lower or upper extremities were also investigated as part of a
      search for generalized effects of LCI. During immersion in ice water the cold
      induced vasodilation (CIVD or Lewis' 'hunting' reaction) was profoundly delayed
      or abolished in the affected limbs. These also showed the lowest skin
      temperatures after 15-20 min of immersion. Additionally, a delayed CIVD was found
      in the unaffected feet of patients with a previous hand injury. TCpO2 resting
      values were decreased in the patients, but oxygen reappearance time, oxygen
      recovery index, postocclusive reactive hyperemia and the venoarterial reflex were
      normal. No capillary abnormalities were found. In conclusion, LCI induces
      disturbances in the CIVD, impairs cold tolerance and increases the risk of future
      cold injuries. These data demonstrate disturbances of reflex mechanisms mediated
      by the central nervous system. Neurophysiologic factors seem to be more important
      than ischemic mechanisms in the pathophysiology of late sequelae from LCI.

PMID- 7635649
TI  - Spatial and temporal variation in laser Doppler flux values in healthy lower
      limbs: comparison between the standard and the multiprobe.
AB  - Skin flow recordings with a laser Doppler instrument have not proven useful for
      evaluation of patients with peripheral arterial occlusive disease. The
      introduction of a probe using seven fibers suggested a reduction in spatial
      variation, but few studies using this multiprobe have been published. The present
      study was designed to compare the multiprobe to the standard probe placed between
      the knee and the first toe, chosen to fit a future study for amputation levels.
      The aim was to evaluate the multiprobe for that purpose. A laser Doppler
      fluxmeter with a standard and a multiprobe was used. Measurements were made in
      five probe sites in lower limbs of healthy volunteers. Each subject was studied
      by 30-second recordings during 60 min with both probes. Statistically (p < 0.001)
      lower flux values were obtained with the multiprobe than with the standard probe.
      The flux variation between the five probe sites was significantly (p < 0.01)
      higher with the standard probe than with the multiprobe, but the temporal
      variation was similar with both probes. The results suggest that the spatial
      variation in widely separated probe sites is reduced with the multiprobe. The
      temporal variation was not found to be reduced.

PMID- 7635650
TI  - Diabetic retinopathy: galactose-fed rat model.

PMID- 7635651
TI  - epsilon-Aminocaproic acid does not inhibit outflow resistance washout in monkeys.
AB  - PURPOSE: To determine whether the anti-fibrinolytic agent epsilon-aminocaproic
      acid (EACA) inhibits the washout of resistance to aqueous humor outflow during
      anterior chamber perfusion in cynomolgus monkeys, as it does in rabbits. METHODS:
      Nine adult ocular normotensive cynomolgus monkeys underwent bilateral anterior
      chamber perfusion with Barany solution, containing 3.8 mM EACA unilaterally.
      Total outflow facility was determined in both eyes simultaneously for
      approximately 4 hours by the two-level constant pressure method. The data were
      analyzed using a linear regression model that tested treated versus control eye
      differences over time against a slope and intercept of 0.0. RESULTS: Outflow
      facility increased and resistance decreased significantly over time similarly in
      both EACA-treated and control eyes; i.e., neither the slopes nor the intercepts
      for facility or resistance, respectively, differed between the eyes over the
      entire 4-hour measurement period or for the initial 90 minutes considered
      separately. The facility increase and resistance decrease as functions of
      perfusion volume also were similar in EACA-treated and control eyes. CONCLUSIONS:
      EACA at this dose does not prevent resistance washout in the cynomolgus monkey,
      in contrast to the rabbit. This species difference may relate to the vastly
      different anatomy and physiology of their outflow pathways.

PMID- 7635652
TI  - Trabecular meshwork in pseudoexfoliation syndrome with and without open-angle
      glaucoma. A morphometric, ultrastructural study.
AB  - PURPOSE: To test the hypothesis that glaucoma in eyes with pseudoexfoliation
      (PEX) syndrome results from blockage of the outflow channels by PEX material,
      melanin granules from the iris pigment epithelium, or both, and to determine the
      origin of intratrabecular PEX material. METHODS: Trabecular meshwork tissue was
      obtained from five surgically enucleated eyes with PEX glaucoma, ten autopsy eyes
      with PEX syndrome without evidence of glaucoma, and six age-matched control eyes.
      Morphometric methods were used to measure the percentage area occupied by open
      spaces, cells, plaque material, PEX material, and melanin granules on electron
      micrograph montages of the entire filtration area and the juxtacanalicular tissue
      (JCT) area. RESULTS: Independent of the presence of glaucoma, most PEX deposits
      were located in the JCT adjacent to the inner and outer walls of Schlemm's canal,
      as well as in the uveal meshwork. Although ultrastructural evidence indicates the
      local production of PEX fibers in the JCT by endothelial and connective tissue
      cells, PEX material in the uveal meshwork is derived partly from the aqueous
      humor. A significant correlation could be established between the presence of
      glaucoma and the amount of PEX material in both the filtration area and the JCT,
      the average thickness of the JCT, and the mean cross-sectional area of Schlemm's
      canal. No significant correlation existed, however, between glaucoma status and
      the concentration of melanin granules or plaque material, and the cellularity.
      CONCLUSION: In addition to a mechanical obstruction by PEX material of
      exotrabecular origin, the apparent production of PEX material by trabecular cells
      may be principally responsible for glaucoma development. Accumulation of locally
      produced PEX material in the JCT, followed by dysfunction of endothelial cells
      and disorganization of JCT and Schlemm's canal, appear to be causative factors in
      the development of a special type of secondary open-angle glaucoma in PEX
      syndrome.

PMID- 7635653
TI  - Molecular characterization of a reduced glutathione transporter in the lens.
AB  - PURPOSE: To characterize glutathione (GSH) transporter in the lens. METHODS: Poly
      (A) +RNA isolated from bovine lens was injected into Xenopus laevis oocytes.
      Oocytes were incubated for 1 hour in either NaCl or sucrose medium containing
      tracer GSH, and cell-associated radioactivity was determined. Glutathione efflux
      was determined in lens mRNA injected oocytes preloaded with GSH. Relationship of
      lens GSH transporter to the two recently cloned sodium-independent hepatic
      membrane GSH transporters was studied by Northern blot and reverse transcription
      polymerase chain reaction (RT-PCR) analyses. Bovine lens mRNA also was probed for
      gamma glutamyl transpeptidase (GGT) by RT-PCR. RESULTS: Uptake of tracer 35S-GSH
      could be demonstrated in X. laevis oocytes injected with poly (A) +RNA from
      bovine lens. Glutathione transport was carrier mediated (Km approximately 1.3 mM)
      and was sodium independent. High-performance liquid chromatography confirmed that
      the molecular form of uptake was predominantly (> 98%) as it was for GSH. Poly
      (A) +RNA-injected oocytes preloaded with 16.5 nmol GSH-oocyte showed GSH efflux
      at a rate of 2.6 nmol/oocyte per hour. When bovine lens poly (A) +RNA was
      hybridized with the cDNA probe for the sodium-independent rat canalicular GSH
      transporter (RcGshT), the transcript for RcGshT was observed. RT-PCR confirmed
      the presence of RcGshT and showed the absence of rat sinusoidal GSH transporter
      (RsGshT) and GGT mRNA in rat lens. CONCLUSIONS: The authors have demonstrated for
      the first time that lens contains mRNA for RcGshT and expresses a low-affinity
      GSH transporter in oocytes. Glutathione efflux from the apical side of the
      anterior epithelium and progressive uptake, and inward efflux into cortical
      fibers, might be explained by expression of RcGshT alone or in combination with
      as yet unidentified GSH transporters.

PMID- 7635654
TI  - The fate of the Golgi apparatus and the endoplasmic reticulum during lens fiber
      cell differentiation.
AB  - PURPOSE: To establish the fate of the Golgi apparatus and the endoplasmic
      reticulum (ER) during lens fiber differentiation. METHODS: Organelles were
      visualized by confocal or electron microscopy. For fluorescence microscopy,
      organelles were labeled with fluorescent probes or antibodies raised against
      organelle-resident proteins. The cytoplasmic volume was reconstructed from
      optical sections using volume rendering techniques. RESULTS: The Golgi apparatus
      was located apically in epithelial cells. In the annular pad, Golgi elements were
      transformed into ribbon-like structures running parallel to the long axes of the
      cells. Toward the lens equator, the Golgi apparatus fragmented. In the lens
      fibers, the Golgi apparatus was detected only in the superficial cells. The ER
      was present as vesicular or tubular elements in both epithelial and cortical
      fiber cells, and ER probes co-labeled the nuclear membrane and revealed that the
      ER and nuclei disappeared coincidentally in the deep cortex. Using a lipophilic
      dye and volume rendering, the relationships between organelles could be evaluated
      in three dimensions. CONCLUSIONS: The Golgi apparatus was not a prominent
      organelle in differentiating lens fibers. In contrast, the ER was more abundant
      and extended to the edge of the organelle-free region, where it was degraded
      along with the nuclei and mitochondria.

PMID- 7635655
TI  - A protective role for glutathione-dependent reduction of dehydroascorbic acid in
      lens epithelium.
AB  - PURPOSE: In view of the antioxidant role of ascorbic acid and the glutathione
      redox cycle in the lens, the authors have studied the relationship of the cycle
      to reduction of the oxidized product of ascorbic acid, dehydroascorbic acid
      (DHA), in lens epithelium. METHODS: Cultured dog lens epithelial cells and intact
      rabbit lenses were exposed to various concentrations of DHA in experiments
      performed at 20 degrees C to minimize hydrolysis of the compound (t1/2 of 5
      minutes at 37 degrees C). Levels of glutathione (GSH) and oxidized glutathione
      (GSSG) were measured in lens cells and whole lens epithelial by electrochemical
      detection. RESULTS: Treatment of lens cells with 1 mM DHA for 0.5 to 3 hours in
      the absence of glucose (glucose is required for the reduction of GSSG through the
      glutathione redox cycle) produced from 60% to complete oxidation of GSH (controls
      contained negligible GSSG) and distinct morphologic changes (cell contraction and
      blebbing), as shown by scanning electron microscopy. Glucose prevented these
      effects and allowed nearly immediate recovery of GSH after DHA exposure in the
      absence of glucose. A dose-dependent response was observed for the formation of
      GSSG in cultured cells from 0.05 to 0.5 mM DHA in the absence of glucose. The
      results of experiments performed with DHA plus an inhibitor of glutathione
      reductase mimicked those obtained using DHA minus glucose. DHA produced a 3- to
      10-fold stimulation of hexose monophosphate shunt activity in cultured lens cells
      and whole lenses, which was prevented by the inhibition of glutathione reductase.
      Treatment of whole lenses with DHA minus glucose also produced oxidation of
      epithelial GSH and was accompanied by the loss of lens transparency. No evidence
      was found for dehydroascorbate reductase activity in the lens epithelium.
      CONCLUSIONS: The exposure of lenses and lens epithelial cells to DHA under
      conditions in which the glutathione redox cycle was compromised resulted in the
      disappearance of GSH in the tissues and the appearance of GSSG. The reduction of
      DHA was shown to be linked to the glutathione redox cycle by a nonenzymatic
      interaction between GSH and DHA. Reduction of DHA in the lens is important
      because of the potential toxicity of this oxidant and/or its degradation
      products.

PMID- 7635656
TI  - Human corneal and conjunctival epithelia express MUC1 mucin.
AB  - PURPOSE: To determine if human corneal and conjunctival epithelial synthesize
      MUC1 mucin, a membrane-spanning mucin present in a variety of simple epithelia.
      METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) was carried out
      to examine the expression of MUC1 mRNA by epithelial cells, using total cellular
      RNA prepared from cultured corneal epithelial cells and conjunctival epithelial
      cells stripped from the ocular surface with nitrocellulose filter paper. Northern
      blot analysis was performed to examine the transcription of MUC1 gene in cultured
      corneal epithelial cells. In situ hybridization histochemistry was performed to
      determine distribution of MUC1 mRNA in ocular surface epithelium. Human milk fat
      globule antibody (HMFG-1) and monoclonal antibody 139H2, which are specific for
      MUC1 core protein, were used in immunoblot analysis, immunohistochemistry, or
      both, to determine the presence and distribution of MUC1. RESULTS: MUC1 mRNA was
      detected in cultured corneal and ex vivo conjunctival epithelial cells by RT-PCR.
      Northern blot analysis showed production of two different sizes of transcripts in
      the cultured corneal epithelium. Expression of MUC1 mRNA was observed in all
      layers of corneal epithelium. By immunoblot analysis, HMFG-1 binding (> 200 kd)
      was detected in human cultured corneal epithelium, and its binding was enhanced
      by neuraminidase pretreatment. Immunohistochemically, HMFG-1 binding was observed
      along the apical membranes of corneal epithelium after neuraminidase
      pretreatment. In the conjunctiva, HMFG-1 and 139H2 binding were detected in the
      basal region and sporadically on the apical surface, but not in the goblet cells.
      CONCLUSIONS: The stratified epithelia of the cornea and conjunctiva synthesize
      MUC1 mucin. This transmembrane mucin may have a role in tear film spread and may
      prevent adhesion of foreign debris, cells, or pathogens to the ocular surface.

PMID- 7635658
TI  - Simulations for FASTPAC and the standard 4-2 dB full-threshold strategy of the
      Humphrey Field Analyzer.
AB  - PURPOSE: This study evaluates the accuracy, reproducibility, and efficiency of
      FASTPAC, a new fast strategy for automated perimetry using 3-dB steps with single
      threshold crossing, compared to the standard 4-2 dB full threshold strategy by
      means of computer simulations. METHOD: An "artificial patient" module was
      developed to create responses to stimuli by a Monte-Carlo technique from a given
      probability distribution. The authors performed 10,200 simulations with threshold
      values ranging from 0 to 50 dB. RESULTS: Results demonstrate an 18% decrease in
      the number of presentations per threshold determination, which is equal to a
      similar reduction in testing time. For both strategies, there is a considerable
      influence of the starting deviation (difference between starting value and actual
      threshold) on threshold error (difference between estimated threshold and actual
      threshold): negative starting deviations lead to negative threshold errors and
      vice versa. This relationship is more pronounced for FASTPAC (slope 0.18 dB/dB, P
      < 0.0001) than for the full-threshold strategy (slope 0.13 dB/dB, P < 0.0001). In
      addition, fluctuations of the determined thresholds, described as the distance
      between the 16th and 84th percentiles of the threshold errors, increase with
      increasing absolute starting deviations. This is particularly true of FASTPAC:
      CONCLUSIONS: The influence of the starting value on the threshold determination
      may lead to a considerable underestimation of visual field defects, accompanied
      by a higher fluctuation. This is an intrinsic property of both staircase
      procedures. FASTPAC, however, is more affected than the standard 4-2 dB full
      threshold strategy. FASTPAC, therefore, provides time reduction at the expense of
      accuracy and reliability.

PMID- 7635657
TI  - Accessory gene regulator controls Staphylococcus aureus virulence in
      endophthalmitis.
AB  - PURPOSE: To evaluate the contribution of toxins to the severity of Staphylococcus
      aureus endophthalmitis. METHODS: Experimental endophthalmitis was established by
      injecting rabbit eyes with wild type S. aureus ISP479 and the isogenic attenuated
      strain, ISP546, defective in expression of the global regulator locus agr. agr
      regulates expression of at least 19 exoproteins that are potentially important in
      the pathogenesis of endophthalmitis. Infections were evaluated using
      electroretinography, slit lamp biomicroscopy, and histology. Two concentrations
      (approximately 10 and 1000 organisms) of bacteria were injected. RESULTS: The agr
      strain consistently resulted in slower loss of b-wave response when compared to
      the wild type strain, irrespective of inoculum size. Clinical signs were less
      severe among the agr- group at 24 and 48 hours when 10 organisms were injected.
      However, when the number of bacteria injected was increased to 1000, earlier
      onset of clinical signs was observed, with both groups showing maximum cell and
      flare and a white fundal reflex at 48 hours after infection. Histologic
      examination of eyes enucleated 36 hours after inoculation revealed that the wild
      type strain induced focal retinal destruction and mild vitritis, whereas eyes
      infected with the agr- strain remained completely normal. Histologic examination
      carried out when loss of B-wave response was 100% revealed that retinal changes
      for both groups could not be distinguished. CONCLUSIONS: These data indicate that
      toxin production by S. aureus contributes to severity of endophthalmitis by
      accelerating the rate of onset of retinal damage. Therefore, toxin-targeting
      therapies instituted early in the course of infection could preserve retinal
      function.

PMID- 7635659
TI  - A window model for spatial integration in human pattern discrimination.
AB  - PURPOSE: A simple model of human visual pattern discrimination was designed and
      tested experimentally. The model is based on two assumptions. First, at any
      glimpse the spatial integration of image information is limited to a window.
      Second, the observer generates a tailored discriminator for the signals in
      question using available information. The model is composed of a spatial
      integration window followed by an ideal discriminator. METHODS: The model was
      tested by comparing its performance with that of human observers in orientation
      and contrast discrimination. Using a two-alternative, forced-choice method, human
      orientation and contrast discrimination thresholds were measured for cosine
      gratings of various areas and spatial frequencies in the presence of two
      dimensional spatial noise. RESULTS: Orientation discrimination thresholds
      decreased considerably with increasing grating area. Thus, there was clear
      spatial integration. However, in contrast discrimination, thresholds appeared to
      decrease only slightly. To make the two tasks comparable, the results also were
      expressed in terms of efficiency. Human efficiency decreased with grating area in
      a similar way in the two tasks. This suggests that the factors limiting spatial
      integration are the same in both tasks. Indeed, the threshold data were explained
      by the model with the same window size in both tasks with good accuracy. The
      absolute performance of the model was approximately equal to that of human
      observers. CONCLUSIONS: The success of the model supports the hypothesis of a
      spatial integration window. It also supports the idea that human observers use
      knowledge about the signals to generate an efficient discriminator.

PMID- 7635660
TI  - Landmark-driven fundus perimetry using the scanning laser ophthalmoscope.
AB  - PURPOSE: To present a new method of performing scanning laser ophthalmoscope
      perimetry that compensates for eye movements so that the correct retinal location
      is tested even if fixation changes. This allows for accurate testing of patients
      with central scotomas and for repeating testing longitudinally at the same
      retinal locations even if central fixation is lost. METHODS: The operator views
      the retina and selects a retinal landmark, such as a vessel bifurcation, that can
      be identified easily. A testing strategy is preselected, and the computer saves
      the landmark and stimulus coordinates. To present each stimulus, the operator
      positions a cursor over the retinal landmark, and the computer adjusts the site
      of presentation of the stimulus for any change in landmark position caused by an
      eye movement. At the conclusion of the testing, the results are displayed in the
      proper retinal location on a fundus image. RESULTS: Sixty-seven eyes with macular
      disease were tested with the landmark-driven method, using the same preplanned
      strategy for each eye for both a bright and a dim stimulus. There was a low rate
      of inconsistent points (seen with dim but not bright stimuli), and virtually all
      of these bordered a dense scotoma. Those eyes with more inconsistent points had a
      significantly greater percentage of dense scotoma points and significantly lower
      visual acuity. The technique significantly corrected error in retinal
      localization resulting from large eye movement. There is no significant rotation
      or magnification change during the procedure, so specifying the change in
      location of one landmark is sufficient to describe movement of the retina. The
      technique is rapid and easy to administer to elderly patients and to children.
      CONCLUSIONS: This technique allows for accurate and repeatable measures of
      retinal sensitivity in specific locations. It is useful in following change over
      time. It can be developed further to allow for fully automated, retinally correct
      testing.

PMID- 7635661
TI  - Ocular pigmentation protects the rabbit retina from gentamicin-induced toxicity.
AB  - PURPOSE: This study was designed to investigate the possibility that gentamicin
      induced retinal toxicity is dependent on ocular pigmentation by comparing the
      effects of the drug on the functional and morphologic integrity of the retina in
      albino and pigmented rabbits. METHODS: In each rabbit, a solution of gentamicin
      sulfate was injected into the vitreous of one eye, and saline was injected into
      the other eye. Retinal function was assessed by electroretinogram (ERG) at
      different time intervals after injection. Retinal structure was examined at the
      light microscopic level. RESULTS: In albino and pigmented rabbits, functional
      retinal damage developed to a maximal level within the first week after
      gentamicin injection. Thereafter, gradual recovery could be seen in eyes that
      suffered less than 80% maximal reduction in the ERG b-wave. For each dose >0.1 mg
      studied, retinal damage was more severe in the albino rabbits than in the
      pigmented ones. The degree of damage was not affected by the level of ambient
      illumination, nor was it reduced by the administration of N-acetylcystein, a free
      radical scavenger, together with gentamicin. CONCLUSIONS: Ocular pigmentation
      partially protects the rabbit retina from the toxic action of gentamicin. This
      protection probably reflects binding of the drug by the melanin, which thereby
      reduces the concentration of the free gentamicin. When the initial gentamicin
      induced retinal damage is expressed in < 80% reduction in the ERG, substantial
      recovery may occur in both strains of rabbits.

PMID- 7635662
TI  - Alpha-2 adrenergic receptors in the bovine retina. Presence of only the alpha-2D
      subtype.
AB  - PURPOSE: To identify and characterize the alpha-2 adrenergic receptor subtypes
      present in the bovine neurosensory retina. METHODS: Radioligand saturation and
      inhibition binding assays were performed with the antagonist radioligands
      [3H]RX821002 and [3H]rauwolscine. RESULTS: [3H]RX821002 bound to a single class
      of receptors with the characteristics of an alpha-2 adrenergic receptor with an
      affinity (KD) of 0.16 nM and a receptor density (Bmax) of 1500 fmol/mg protein.
      Correlation of the affinities (pKi values) for nine antagonists in the bovine
      neurosensory retina with the alpha-2D receptor of the bovine pineal gave a
      correlation coefficient of 0.99. The correlation coefficients for the alpha-2A
      (0.84), alpha-2B (0.36), and alpha-2C (0.39) subtypes were much lower. The
      presence of a minor population of alpha-2B or alpha-2C receptors was excluded.
      CONCLUSIONS: A high density of alpha-2D adrenergic receptors is present in the
      bovine neurosensory retina. Neither the alpha-2B nor the alpha-2C subtype is
      detectable.

PMID- 7635663
TI  - Effects of adenosine on ocular blood flow.
AB  - PURPOSE: To determine the effect of intravascular adenosine on blood flow in the
      ocular fundus and to examine indirectly whether the blood-brain barrier to
      adenosine, which exists in the cerebrovasculature of the cat, is present in the
      eye of this animal. METHODS: The noninvasive techniques of laser Doppler
      flowmetry and velocimetry along with fundus photography were used to measure the
      change in optic nerve head and choroidal and retinal blood flow during
      intravenous infusions of 0.18 and 0.6 mg/kg per minute of adenosine. RESULTS:
      Infusions of adenosine induced significant increases in choroidal blood flow (60%
      with 0.6 mg/kg per minute) but not in optic nerve head or retinal blood flows.
      CONCLUSIONS: The lack of effect of intravenously infused adenosine on the optic
      nerve and retinal circulations is most likely caused by the tight junctions in
      the vessels of these vascular beds, which prevent adenosine from reaching its
      receptors. Perivascular adenosine in the choroid most likely accounts for the
      increase in blood flow in this tissue.

PMID- 7635664
TI  - Retinal effects of ultrashort laser pulses in the rabbit eye.
AB  - PURPOSE: To evaluate the effects of ultrashort laser pulses from femtoseconds to
      nanoseconds on the retinas of live rabbit eyes and to determine the energy
      requirements for visible lesion development. METHODS: The retinal effects of
      laser exposures were examined for laser exposures with pulsewidths ranging from 4
      ns to 90 fs, with visible wavelengths of 532 nm for durations > 5 ps and 580 nm
      for durations < 5 ps. The authors examined and scored all laser impact sites in
      the retina ophthalmoscopically--with fundus photography and with fluorescein
      angiography--to identify evidence of visible laser effects. RESULTS: The laser
      energy required for retinal minimal visible lesions was found to be slightly less
      for pulsewidths < 5 ps and varied from 5 microJ at 4 ns to 1.1 microJ at 90 fs
      for the 1-hour ophthalmoscopic reading. Lesions from higher energy pulses (7 to
      120 microJ) were examined at all pulsewidths. For 90-fs high-energy pulse
      delivery, an increased intensity of retinal lesions and the development of
      several subretinal hemorrhages were demonstrated at peak energies of 30 microJ.
      Fluorescein angiography was found to be much more sensitive as an indicator of
      retinal damage for both femtosecond pulsewidths. CONCLUSIONS: The low energies
      required for visible lesion production in live rabbit eyes raise new questions
      surrounding ultrashort pulse propagation in ocular media, energy deposition at
      the retina, and mechanisms limiting retinal damage from ultrashort laser pulses.

PMID- 7635665
TI  - Intersegmental fusion in vertebrate rod photoreceptors. Rod cell structure
      revisited.
AB  - PURPOSE: To determine the cause of intersegmental fusion--a fusion between the
      plasma membranes of the inner and outer segments--in vertebrate rod cells.
      METHODS: Rod cells from adult salamander, frog, and rat retinas were examined
      with electron microscopy. The fine structure of fusion and the frequency of
      occurrence were assessed in three types of preparations (intact eyeballs, eyecup
      preparations, and neural retinas detached from the retinal pigmented epithelium).
      The effects of temperature, depolarization, and calcium were examined in isolated
      neural retinas by maintaining retinas in culture under defined conditions.
      Retinas from anesthetized animals also were examined. RESULTS: Intersegmental
      fusion in rod cells was consistently observed in all species after retinal
      detachment and maintenance in a standard Ringer's solution for 20 to 30 minutes.
      The amount of fusion seen in isolated amphibian retinas was sensitive to a number
      of factors: Elevated temperature increased the number of fused rod cells, whereas
      high KCl, low CaCl2, and Tricaine, which has calcium-related effects, reduced or
      prevented fusion. In attached retinas, fusion was seen infrequently; the
      incidence of fused cells in amphibian eyecup preparations, however, could be
      increased by incubation in the cold. The extensive continuity between the inner
      and outer segments created by their fusion did not disrupt intracellular
      structure. Moreover, the fusion seemed to be reversible with time. CONCLUSIONS:
      Intersegmental fusion is a feature of vertebrate rod cells. Although seen
      predominantly after retinal detachment, it is influenced by factors that affect
      other well-known exoplasmic membrane fusions. Thus, it may be one of the many
      regulated membrane fusion-fission events within the rod photoreceptor.

PMID- 7635666
TI  - Clinical expression correlates with location of rhodopsin mutation in dominant
      retinitis pigmentosa.
AB  - PURPOSE: To determine whether severity of retinitis pigmentosa caused by dominant
      rhodopsin mutations depends on the location altered by the mutation. METHODS:
      Data from 128 patients (age range, 7 to 73 years), each with 1 to 27 rhodopsin
      mutations, were analyzed. To approximate normal distributions, visual acuities
      were converted to ranks and then to the normal form, kinetic visual fields to a
      V4e test light were converted to equivalent diameters, and dark-adapted
      sensitivities to an 11 degrees diameter stimulus and electroretinogram (ERG)
      amplitudes to full-field 0.5-Hz and 30-Hz flashes were converted to common
      logarithms. Each of these measures was then regressed on age, refractive error
      (for the ERG), and domain (intradiscal, transmembrane, or cytoplasmic) or codon
      number of the opsin molecule altered by the mutation. RESULTS: All five measures
      of function varied significantly with the domain (P < or = 0.0007) or codon
      number (P < 0.0001) altered by a mutation; visual acuity, visual field diameter,
      dark-adapted sensitivity, and ERG amplitudes were highest for mutations altering
      the intradiscal domain or low-numbered codons and lowest for mutations altering
      the cytoplasmic domain or high-numbered codons. CONCLUSIONS: These data indicate
      that severity of disease correlates with the location of the amino acid residue
      altered by a rhodopsin mutation in dominant retinitis pigmentosa.

PMID- 7635667
TI  - Retinal tissue oxygen tension in normoxic cats under enflurane anesthesia.
AB  - PURPOSE: General anesthesia reduces systemic blood pressure and, thus, ocular
      perfusion pressure (at constant intraocular pressure). Whether this reduction in
      ocular perfusion pressure produces retinal hypoxia is unknown. To answer this
      question, the authors measured inner retinal oxygen tension in cats under general
      enflurane anesthesia at three clinically relevant levels of anesthesia under
      normoxic conditions. METHODS: Polarographic oxygen microelectrodes were used to
      measure inner retinal oxygen tension in cats under enflurane anesthesia at 21%
      inspired oxygen tension. Measurements were made in the preretinal vitreous body
      within 100 to 200 microns of the internal limiting membrane of the retina. Three
      levels of enflurane anesthesia were used: 1.2%, 2.4%, and 3.6%, corresponding to
      0.5, 1.0, and 1.5 minimal alveolar concentration. Intraocular pressure of the
      cats was maintained at a constant normal level throughout the experiments.
      RESULTS: Under normoxic conditions, inner retinal oxygen tension remained
      unchanged or increased slightly as ocular perfusion pressure decreased with
      deeper levels of enflurane anesthesia. CONCLUSION: Commonly used surgical levels
      of enflurane general anesthesia do not cause hypoxia of the inner retina in cats
      breathing 21% inspired oxygen. This may be the result of preservation of retinal
      vascular autoregulation under enflurane anesthesia, retinal vasodilatation
      secondary to a direct smooth muscle relaxing effect of enflurane, or decreased
      retinal oxygen use under enflurane anesthesia.

PMID- 7635668
TI  - Absolute quantitation of brain 1H nuclear magnetic resonance spectra. Comparison
      of different approaches.
AB  - RATIONALE AND OBJECTIVES: Three different calibration techniques of 1H localized
      nuclear magnetic resonance (NMR) spectra were applied to a group of healthy
      volunteers. Absolute concentrations of the metabolites and their standard
      deviations were compared, and the clinical feasibility of these calibration
      technique is discussed. METHODS: Eighteen healthy volunteers were included in the
      study. Both water and creatine were used as internal standard, and a pertinent
      solution of metabolites was used as an external standard. The T2 relaxation times
      of the brain metabolites were evaluated in each examination. RESULTS AND
      CONCLUSIONS: The concentrations obtained using water as an internal standard and
      using an external standard are very similar, and the first of these methods show
      smaller standard deviations. The authors' results show that the use of creatine
      as an internal standard may induce systematic errors in absolute calibration
      because of the uncertainty on the true creatine concentration.

PMID- 7635669
TI  - Automated and accurate assessment of the distribution, magnitude, and direction
      of pincushion distortion in angiographic images.
AB  - RATIONALE AND OBJECTIVES: Pincushion distortion continues to be a potential
      problem for the accurate assessment of arterial and catheter dimensions from x
      ray angiograms. The authors investigate whether the distortion of state-of-the
      art intensifiers is yet small enough to be neglected, and whether the
      rotation/angulation of the x-ray system plays a significant role. METHODS: The
      location and degree of distortion from x-ray images of a centimeter grid, which
      is positioned against the input screen of the image intensifier, are assessed
      automatically using image processing techniques. A value for the maximum amount
      of change in the distortion vector field is derived that allows the estimation of
      the maximum relative error associated with a diameter measurement uncorrected for
      pincushion distortion. RESULTS: The accuracy of the algorithm itself was assessed
      by rotating and translating the centimeter grid under the image intensifier at
      anteroposterior position. For the distortion vector length, the standard
      deviation in the measurement of the distortion areas was found to be 3.7 cm2
      (1.3% of the total area). For the gradient values, the standard deviation was 2.2
      cm2 or 0.75% of the total image intensifier area. In the second evaluation study,
      the centimeter grid was fixed onto the input screen of the image intensifier, and
      the gantry was rotated to span all possible positions of the system. In this
      case, the changes in measured areas were often much larger (up to 51.25 cm2 for a
      9-inch image intensifier, equivalent to 15.6% of the total image intensifier
      area) than the standard deviations that had been found in the first evaluation
      study. CONCLUSIONS: The distortion is highly dependent upon the actual spatial
      position of the image intensifier, and correcting for pincushion distortion may
      therefore introduce larger errors than leaving the measurements uncorrected.

PMID- 7635670
TI  - Magnetic resonance imaging as a monitor of changes in the irradiated rat brain.
      An aid in determining the time course of events in a histologic study.
AB  - RATIONALE AND OBJECTIVES: Optimal dose schedules and total dose of ionizing
      radiation for human central nervous system malignancy are not known. An animal
      model has been developed for the investigation of rat central nervous system
      response to proton irradiation using magnetic resonance imaging (MRI). A clinical
      MRI device was used to monitor the response of the rat brain after irradiation as
      a possible indicator for histologic injury as a function of time and dose.
      METHODS: Single-dose fractions of protons were delivered to the left brain of 25
      adult Sprague-Dawley rats. T1- and T2-weighted images were obtained using a 1.5-T
      MRI device via a 12-cm diameter coil at 4- to 6-week intervals after irradiation.
      Coronal images were evaluated by visual inspection and relaxation maps comparing
      the control and irradiated hemispheres. Histologic review was conducted on all
      rats' brains after death. RESULTS: Proton irradiation was delivered successfully
      to only the left brain of the animals. Histologic review confirms the location
      and extent of tissue damage demonstrated on MRIs obtained in vivo. Statistically
      significant differences were seen in the T2-weighted relaxation times in the
      irradiated cerebral hemisphere compared with the unirradiated hemisphere.
      CONCLUSION: The proton hemibrain rat model can be used to test treatment
      schedules of irradiation for central nervous system response using MRI to
      noninvasively document early and late effects within the same animal.

PMID- 7635671
TI  - Radiocontrast nephrotoxicity. A review.

PMID- 7635672
TI  - Influence of viscosity on WIN 39996 as a contrast agent for gastrointestinal
      magnetic resonance imaging.
AB  - RATIONALE AND OBJECTIVES: The authors discuss the influence of viscosity on the
      imaging properties of WIN 39996 suspension. WIN 39996 suspension is a
      magnetically susceptible iron ferrite that provides negative (darkening) contrast
      enhancement in magnetic resonance imaging of the gastrointestinal tract. METHODS:
      The viscosity of WIN 39996 suspension was altered by various stress conditions (1
      week to 4.5 months storage at temperatures of 5 degrees to 70 degrees C) or by
      various amounts of xanthan gum. Magnetic resonance imaging was performed in vitro
      on phantoms and in vivo on the gastrointestinal tract of anesthetized dogs.
      RESULTS: The results indicated that in vitro and in vivo imaging efficacies of
      WIN 39996 suspension depended on the viscosity, irrespective of the means by
      which the viscosity was altered. Specifically, the imaging quality was suitable
      at viscosities > or = 36.6 cp for in vitro imaging, and > 25 cp for in vivo
      imaging. The lower in vivo viscosity limit for magnetic resonance imaging
      compared with the in vitro limit may be due to gastrointestinal peristaltic
      activities continuously mixing the WIN 39996 suspension to prevent gravitational
      settling, and the enhancement of signal blackening by intraluminal WIN 39996 that
      was above and below the plane of image. CONCLUSIONS: It is speculated that the
      imaging quality of WIN 39996 suspension depends on the degree of dispersion of
      the magnetically susceptible iron ferrite in the WIN 39996 suspension, and that a
      minimum viscosity is needed to ensure such dispersion.

PMID- 7635673
TI  - Ultrasound assessment of liver and kidney brightness in infants. Use of the gray
      level histogram.
AB  - RATIONALE AND OBJECTIVES: Ultrasonic image analysis aims to provide information
      related to tissue histology. Routine ultrasonography uses subjective criteria for
      analysis. Quantitation of the image is expected to aid diagnosis and may be
      helpful in follow-up of pathology. The authors describe normal findings in infant
      liver and kidney. METHODS: Texture parameters derived from the gray-level
      histogram and the first order statistics from the ultrasound images of the liver,
      right kidney, and a tissue-mimicking phantom in 50 newborn infants were studied.
      RESULTS: A set of normal values for mean and standard deviation of the histogram
      for infant liver and kidney was established. Results of a time-related study
      indicate that in infants the liver is not a good internal standard for tissue
      characteristic comparison. CONCLUSIONS: The method described and results obtained
      provide a basis of normality for further studies of pathology in infant renal and
      hepatic disease.

PMID- 7635674
TI  - Animal experimental myelography in the pig. A comparison between iohexol and
      iotrolan.
AB  - RATIONALE AND OBJECTIVES: The authors compared the effects of a nonionic
      monomeric, iohexol (Omnipaque, 300 mg I/ml), and a nonionic dimeric, iotrolan
      (Isovist, 300 mg I/ml), contrast medium in the spinal subarachnoid space of the
      pig. METHODS: Lumbar and lateral C1-C2 punctures were performed in 10 pigs. Ten
      milliliters iohexol or iotrolan were injected via the lumbar needle. Blood
      pressure, electrocardiogram, intravesical pressure, and cerebrospinal fluid
      pressure were recorded during the injections and at intervals for 4 to 5 hours
      after the injections. Blood samples were taken at 30, 60, 120, 180, 240, and 300
      minutes after the injections and analyzed for iodine concentration. RESULTS: No
      changes were seen during the injections, and there were no differences in the
      blood pressure, cerebrospinal fluid pressure, electrocardiographic recordings, or
      in the plasma iodine concentrations during the first 4 to 5 hours after the
      injections. Short-lasting, rhythmic bladder contractions were seen during some
      injections with both iohexol and iotrolan. CONCLUSION: Both iohexol and iotrolan
      were well tolerated, and there was no significant difference between them. and
      there was no significant difference between them.

PMID- 7635675
TI  - Absolute phasic blood flow measurement in the brain using digital subtraction
      angiography.
AB  - RATIONALE AND OBJECTIVES: In this study, an angiographic method using first-pass
      distribution analysis was used for quantification of phasic volumetric blood
      flow. Studies were conducted in an angiographic perfusion phantom and in an
      animal model (rabbit) after intraarterial injection of contrast material.
      METHODS: Digital subtraction angiography and first-pass distribution algorithm
      were used to assess the absolute volumetric flow rates. The method, based on the
      conservation of contrast material in successive angiographic images, uses the
      videodensitometric information in the arterial bed. Measurements were made by
      summing the pixel values in the region of interest, covering the whole perfusion
      bed. A contrast pass curve was generated for a sequence of images to obtain
      instantaneous volumetric flow rates. RESULTS: Instantaneous and mean absolute
      volumetric flow measurements made in the angiographic perfusion phantom and the
      common carotid artery of the animal models correlated well with validation
      measurements made using ultrasound flowprobes. The measured (M) and known (K)
      flow rates in the carotid artery were related by M = 0.87 K + 2.50 mL/minute (r =
      0.96, standard error of the estimate = 3.79 mL/minute, n = 25) and M = 0.92 K -
      1.00 mL/minute (r = 0.98, standard error of the estimate = 4.04 mL/minute, n =
      38) using the videodensitometric and entrance vessel calibration techniques,
      respectively. Conclusion. Results demonstrate the potential use of the first-pass
      distribution method in conjunction with digital subtraction angiography for
      measuring phasic arterial blood flow in vivo.

PMID- 7635676
TI  - Magnetic resonance bone densitometry. Comparison of different methods based on
      susceptibility.
AB  - RATIONALE AND OBJECTIVES: Three different magnetic resonance techniques for the
      assessment of the density of trabecular bone are presented and compared. METHODS:
      All methods are based on the susceptibility difference between marrow and bony
      components. Localized spectroscopic (PRESS single voxel spectroscopy) and two
      different imaging approaches (FLASH gradient echo imaging and MAGSUS imaging) are
      demonstrated to be sensitive to the trabecular structures on application to the
      distal femur of a healthy volunteer. This region was chosen because a continuous
      rarefication of the trabecular density from the epiphysis to the metaphysis
      occurs physiologically. In addition, results from the heel-bones of five young
      healthy volunteers were compared with data from three patients with severe
      osteoporosis. RESULTS: All methods allowed differentiation between the two
      groups. Advantages and disadvantages of the methods concerning spatial
      resolution, preparation and measuring time, necessity of postprocessing, problems
      with shim adjustment, and occurrence of several chemical shift components are
      reported. The MAGSUS technique combines simple application and avoidance of
      postprocessing for at least qualitative assessment of bone density with
      sufficient spatial resolution. CONCLUSIONS: A reliable assessment of osteoporosis
      by magnetic resonance is possible in peripheral marrow regions of adults. Further
      studies are needed to establish standard measuring protocols.

PMID- 7635677
TI  - Initial experience with percutaneous balloon mitral commissurotomy.
AB  - Percutaneous Transvenous Mitral Commissurotomy (PTMC) is an alternative to
      surgical mitral valvuloplasty for treatment of selected patients with rheumatic
      mitral stenosis. We report our initial experience with the technique in 10
      patients. The procedure was successful in all patients. There were no major
      complications. Mitral valve area increased from a mean (+/- SD) of 0.95 +/- 0.2
      to 2.18 +/- 0.8 cm2. Transmitral pressure gradient fell from 12 +/- 8 to 4 +/- 5
      mmHg while New York Heart Association functional class improved by 1 grade or
      more in all patients. PTMC is a safe and cost effective alternative to surgical
      mitral valvotomy in appropriately selected cases.

PMID- 7635678
TI  - Diabetes mellitus in an adult cystic fibrosis population.
AB  - Medical records of 132 patients attending an adult cystic fibrosis (CF) clinic
      were analysed to define the prevalence and clinical significance of diabetes
      mellitus (DM) in CF. Eighty four (63.6%) had normal blood glucose levels, 30
      (22.8%) had hyperglycaemia only during intercurrent illness and 18 (13.6%) had
      DM. No significant differences were noted between the diabetic and non-diabetic
      groups for age, gender, height, weight, body mass index (BMI), forced expiratory
      volume in one second (FEV1) and forced vital capacity (FVC) and pancreatic
      supplementation. Patients with hyperglycaemia during intercurrent illness had
      significantly lower BMI, FEV1% and FVC% than those with normal blood glucose
      levels. Of the diabetics four were managed on diet, three received oral
      hypoglycaemic agents and eleven were insulin requiring. The prevalence of DM in
      CF is considerable, severity of CF does not correlate with development of overt
      DM, and CF patients should be screened for DM by an oral glucose tolerance test
      on reaching adulthood.

PMID- 7635679
TI  - Acoustic neuromas: a review of 58 patients and correlation of tumour-size to the
      outcome.
AB  - Fifty eight patients with acoustic neuromas, who presented over a six year period
      were reviewed. These patients were sub divided into three groups according to
      their tumour size. Group A comprised of 21 patients with lesions less than 2 cm
      in diameter, of which 83% presented in the last two years. Group B comprised of
      30 patients with lesions measuring 2-4 cm, of which 43% presented in the last two
      years. Group C included 7 patients with lesions greater than 4 cm in size, of
      which 14% presented in the corresponding period. The relative increase in the
      number of patients in Group A and decrease in Group C over the years is a direct
      reflection of heightened clinical awareness and increased usage of magnetic
      resonance imaging for diagnosis. Complete surgical excision was achieved in 20/21
      patients in Group A and 4/7 patients in Group C, with an overall complete
      excision rate of 81%. The overall facial nerve preservation rate was 81% of which
      20/21 patients were in Group A, 23/30 in Group B and 4/7 in Group C. The surgical
      morbidity ranged from 10% in Group A to 28% in Group C. There were no deaths in
      Group A compared to two each in Group B and Group C. This emphasises the
      importance of early detection and treatment of acoustic neuromas when they are
      small.

PMID- 7635681
TI  - HRT and cardiovascular disease.

PMID- 7635682
TI  - Routine management of the woman on HRT.

PMID- 7635683
TI  - Treatment of osteoporosis.

PMID- 7635680
TI  - Duplication (12p) syndrome--a family.
AB  - We report the following cases of Duplication (12p) Syndrome. This is a rare
      entity which may present with developmental delay, dysmorphic features and
      malformations.

PMID- 7635684
TI  - The silence of violence: lets not talk about abuse during pregnancy.

PMID- 7635685
TI  - Non-melanoma skin cancer.

PMID- 7635686
TI  - Respiratory pathogens: resistance patterns.

PMID- 7635687
TI  - Treating angina and hypertension with ISTIN.

PMID- 7635688
TI  - Suicide, road traffic and cancer deaths among the young in Ireland.
AB  - Every young suicide occurring in Ireland from 1976 to 1993 was reviewed and
      comparisons made with deaths from road traffic accidents and deaths from cancer.
      As well as this, suicide occurring in the under 25 age group in a series of a
      hundred consecutive suicides were examined to see what methods were used and what
      treatments received. Whereas cancer deaths and road traffic deaths are falling
      among the young, suicide among young Irish males continues to rise. Few appear to
      have elected for psychiatric treatment in the year before their death. The
      research implications of these findings are discussed.

PMID- 7635689
TI  - Analysis of care of HIV positive patients: hospital and general practice
      components.
AB  - Fifty-seven HIV positive adults (mostly injecting drug users) attending two inner
      city Dublin general practices were followed for one year to identify the general
      practice and hospital components of their care. Many patients had advanced
      disease; during the year 10/57 (17.5%) died. The group made a median of seven
      visits to general practice (range 0-35) and two visits to hospital HIV clinics
      (range 0-21). A quarter of the group (14/57) was seen only in general practice
      and did not attend hospital; only two patients did not attend either the HIV
      Clinic or the GP during the year. Hospital admission was needed for 15/57 (26.3%)
      patients on a total of 31 occasions with an average length of stay of 10 days per
      admission; 80% of these admissions were generated by 10 patients with AIDS. The
      indication for almost all admissions was serious physical illness or diagnostic
      or therapeutic procedure. Patients with symptomatic or advanced HIV disease
      required a higher level of care than those with asymptomatic disease. It is
      essential that the agencies involved in meeting this level of demand be
      adequately resourced and that they liaise closely.

PMID- 7635690
TI  - Physician neutrality and patient autonomy in advance directive decisions.

PMID- 7635691
TI  - Medical decisionmaking for older adults in institutional settings: is beneficence
      dead in an age of risk management?

PMID- 7635692
TI  - The politics of medical futility.

PMID- 7635693
TI  - Section 1983 civil liability of prison officials for denying and delaying
      medication and drugs to prison inmates.

PMID- 7635694
TI  - In re Gordy.

PMID- 7635695
TI  - Long-term prevention of recurrent hepatitis B virus after liver transplantation.
AB  - Hepatitis B virus (HBV) reinfection is a major threat to HBV-infected patients
      undergoing orthotopic liver transplantation. Eleven HBsAg-positive patients with
      end-stage liver disease underwent liver transplantation. All were treated with
      high doses of anti-HBs antibodies, initiated first during the anhepatic stage of
      the operation and continued every 2-8 weeks thereafter according to anti-HBs
      levels in the serum. Attempts were made to keep anti-HBs levels above 400 IU/ml.
      Patients were followed for 8-42 months and only one of them had any evidence for
      recurrence of HBV infection 40 months post-transplantation. We conclude that
      continuous administration of anti-HBs and maintenance of high levels of anti-HBs
      in the serum prevent recurrence of HBV infection.

PMID- 7635696
TI  - Low density lipoprotein-cholesteryl ester-derived linoleic acid is mainly
      incorporated into the phospholipid component of the macrophages.
AB  - The cellular metabolism of the cholesterol in the low density lipoprotein
      cholesteryl ester (LDL-CE) moiety is well characterized, whereas the cellular
      fate of the fatty acid (mainly linoleic acid) in the LDL-CE has not been studied
      in detail. The distribution of the LDL-CE-derived linoleic acid among cellular
      lipids was studied in J-774 A.1 macrophages, using LDL that was radiolabeled in
      the linoleic acid of its CE moiety. Macrophages were incubated with radiolabeled
      LDL for 4 h at 4 degrees C, washed and further incubated for up to 24 h at 37
      degrees C in a fresh medium (without LDL). The distribution of the linoleic acid
      among cellular lipids was then analyzed. After 20 min of incubation, most of the
      linoleic acid was found in the CE fraction as a constituent of the internalized
      LDL, and the CE-associated linoleate was progressively decreased. In parallel,
      the linoleic acid was found to be esterified into the macrophage phospholipids
      (mostly in the macrophage phosphatidyl choline fraction), accounting for up to
      62% of the total cellular labeled linoleic acid after 24 h of incubation. We
      conclude that the fatty acid derived from the hydrolysis of the LDL-CE moiety in
      macrophages is mainly incorporated into the cellular phospholipids where it can
      serve for various cellular metabolic processes.

PMID- 7635697
TI  - Surgery in chronic dialysis patients.
AB  - During recent years there has been a continuous increase in the number of
      patients with end-stage renal failure who require long-term dialysis. The purpose
      of this retrospective work was to look at the number and type of operations
      performed and the postoperative outcome and complications that may be typical for
      these patients. This report details our experience with surgery in chronic
      dialysis patients, focusing mainly on major surgical procedures. During 21 years
      (1972-93) 22 patients on long-term hemodialysis or peritoneal dialysis underwent
      44 operations. All access operations and parathyroidectomies were excluded. Each
      patient underwent between 1 and 6 operations; 27 (61.4%) operations were elective
      and 17 (38.6%) were emergencies. The most common type of operation performed was
      abdominal surgery and hernia repair; the others, in decreasing order, were
      urological operations, amputations, and vascular surgery. Postoperative
      complications occurred in 54% of the operations, the most common being
      hyperkalemia in 32%, infectious complications in 16%, and bleeding in 11%. One
      patient (2%) died postoperatively; the cause was most probably secondary to
      hyperkalemia and a fatal arrhythmia. From a review of the literature and from the
      results of our study it appears that surgery in uremic patients can be performed
      with acceptable results in terms of morbidity and mortality rates. Complications,
      such as hyperkalemia, a fall in blood pressure, and bleeding, are expected and
      preventive measures should therefore be taken. Perioperative measures are
      recommended to minimize complications.

PMID- 7635698
TI  - Acute subdural hematoma following disseminated intravascular coagulation
      associated with an obstetric catastrophe.
AB  - The clinical, laboratory, radiological and operative recordings of a patient with
      disseminated intravascular coagulation (DIC) related to therapeutic abortion is
      reported. During a comatose state following respiratory arrest, anisocoria with
      right dilated unreactive pupil and decerebration signs appeared. A brain CT scan
      showed a right frontotemporal hemorrhage. On surgical intervention a subdural
      hematoma was found and removed. The patient remained in a persistent vegetative
      state. The rarity of subdural hematoma complicating DIC is presented and the
      causes of intracranial bleeding in obstetrics are reviewed.

PMID- 7635699
TI  - Cost analysis of in vitro fertilization.
AB  - In vitro fertilization (IVF) has become a routine tool in the arsenal of
      infertility treatments. Assisted reproductive techniques are expensive, as
      reflected by the current "take home baby" rate of about 15% per cycle, implying
      the need for repeated attempts until success is achieved. Israel, today is facing
      a major change in its health care system, including the necessity to define a
      national package of health care benefits. The issue of infertility and whether
      its treatment should be part of the "health basket" is in dispute. Therefore an
      exact cost analysis of IVF is important. Since the cost of an IVF cycle varies
      dramatically between countries, we sought an exact breakdown of the different
      components of the costs involved in an IVF cycle and in achieving an IVF child in
      Israel. The key question is not how much we spend on IVF cycles but what is the
      cost of a successful outcome, i.e., a healthy child. This study intends to answer
      this question, and to give the policy makers, at various levels of the health
      care system, a crucial tool for their decision-making process. The cost analysis
      includes direct and indirect costs. The direct costs are divided into fixed costs
      (labor, equipment, maintenance, depreciation, and overhead) and variable costs
      (laboratory tests, chemicals, disposable supplies, medications, and loss of
      working days by the couples). The indirect costs are the costs of premature IVF
      babies, hospitalization of the IVF pregnant women in a high risk unit, and the
      cost of complications of the procedure. According to our economic analysis, an
      IVF cycle in Israel costs $2,560, of which fixed costs are about 50%. The cost of
      a "take home baby" is $19,267, including direct and indirect costs.

PMID- 7635700
TI  - Familial Mediterranean fever in the "Chuetas" of Mallorca--origin in inquisition?
AB  - The aim of our study was to compare the features of familial Mediterranean fever
      (FMF) in Mallorcan "Chuetas" with those in non-Ashkenazi Jews in Israel. The
      clinical and laboratory data of FMF were evaluated in a recently identified
      cluster of 50 FMF patients from Mallorca (the Chuetas) and 45 patients from
      Israel. We found that the prevalence and clinical manifestations of FMF were
      similar among the Chuetas and the Israeli group. Furthermore, in contrast to
      other ethnic groups with FMF, joint involvement was quite common in both the
      Chuetas (70%) and the Israeli group (75%). The Chuetas are descendants of
      Mallorcan Jews who emigrated from Spain to the island in the 12th century. The
      non-Ashkenazi Jews originated mainly in North Africa and are descendants of
      refugees who escaped from Spain as a result of the Inquisition in the 15th
      century. We suggest that the non-Ashkenazi Jews and the Chuetas may have a common
      gene defect for FMF.

PMID- 7635701
TI  - High prevalence of thyroxine-binding globulin deficiency among Bedouin infants in
      southern Israel.
AB  - A high prevalence of thyroxine-binding globulin deficiency was found among
      Bedouin newborns in the Negev area (southern Israel) during a study lasting 2
      years. This prevalence is significantly higher than those reported in other
      populations. Moreover, thyroxine-binding globulin deficiency was found to be more
      common than congenital hypothyroidism among the Bedouin. The results of thyroxine
      binding globulin analysis in four patients may suggest the coexistence of at
      least two different mutations among the Bedouin population.

PMID- 7635702
TI  - The origin of the FMF gene.

PMID- 7635703
TI  - Recent advances in diagnosis and therapy in Gaucher's disease.

PMID- 7635704
TI  - Resistance to activated protein C: a new etiology for hypercoagulable states.

PMID- 7635705
TI  - Basophils in allergy.

PMID- 7635707
TI  - Where nursing regulation begins and ends.

PMID- 7635706
TI  - Mandatory continuing education for nurses repealed in Colorado.

PMID- 7635708
TI  - Project ASSIST. Preparation of paraprofessionals working with school nurses
      serving children and youth with special health needs.

PMID- 7635709
TI  - National council's nursing practice and education committee develops model for
      collaboration.

PMID- 7635710
TI  - Regulatory considerations regarding accepting orders.

PMID- 7635711
TI  - New York's Regents College. An outcome based approach to nursing education.

PMID- 7635712
TI  - Delegation in nursing.

PMID- 7635713
TI  - Changes incorporated into NCLEX-RN Test Plan.

PMID- 7635714
TI  - On the NCLEX horizon. The future of nurse licensure examinations.

PMID- 7635715
TI  - New NCLEX-RN passing standard may be implemented.

PMID- 7635716
TI  - A multivariate study of headache associated with ischemic stroke.
AB  - Thirty-four percent of 182 ischemic stroke patients registered during 1 year in a
      prospective hospital stroke data base complained of headache within a 72-hour
      interval of stroke onset. Headache was more common in patients under 70 years of
      age, in nonsmokers, in those with a past history of migraine, and in subjects
      presenting transient loss of consciousness, nausea/vomiting, or visual field
      defects. Headache was more frequent in vertebrobasilar (57%) than in carotid
      (20%) territory strokes, more so in posterior cerebral artery (90%) and
      cerebellar infarcts (80%), and was infrequent in subcortical infarcts (7%) and
      lacunes due to single perforator disease (9%). In multiple regression analysis,
      vertebrobasilar stroke (odds ratio 6.9), lacuanr stroke (odds ratio 0.06), and
      past history of migraine (odds ratio 6.7) were significant independent predictors
      of headache, suggesting that ischemic stroke location is the major determinant of
      stroke-associated headache, most probably related to activation of the
      trigeminovascular system, whose threshold may be modified by individual
      susceptibility.

PMID- 7635717
TI  - Development of a brief 24-hour migraine-specific quality of life questionnaire.
AB  - The objective of this study was to develop a questionnaire to assess the short
      term quality of life decrements associated with an acute migraine headache
      attack. A total of 101 potential quality of life items were generated by
      interviewing migraineurs and migraine specialists and reviewing the literature.
      To reduce the items, 76 migraineurs (18 years and older) were asked to identify
      which of the 101 items affected their quality of life in the 24 hours following
      onset of a migraine and to rate them on a five-point scale from "not very
      important" to "extremely important." Reduction of the 101 items to a 15-item
      questionnaire was performed by evaluating the results of subject-perceived
      importance (number of times an item was chosen x mean importance score) in
      combination with principal components analysis. Five domains were identified: (1)
      work functioning, (2) social functioning, (3) energy/vitality, (4) migraine
      headache symptoms, and (5) feelings and concerns. Each domain has three items and
      the correlation between the five domains, as measured by the Spearman correlation
      coefficient, ranged from 0.08 to 0.38 suggesting minimal overlap. The brief
      migraine quality of life questionnaire was pilot-tested in two groups of 10
      migraineurs and revised to improve clarity.

PMID- 7635718
TI  - Validation of a new quality of life questionnaire for acute migraine headache.
AB  - A brief migraine-specific quality of life questionnaire was developed to assess
      the quality of life decrement associated with an acute migraine attack in the 24
      hour period following headache onset. The migraine quality of life questionnaire
      has 15 questions across five domains (work functioning, social functioning,
      energy, concerns, and symptoms). A prospective, observational study was conducted
      to evaluate the characteristics of internal consistency, construct and
      discriminant validity, and responsiveness of the migraine quality of life
      questionnaire. One hundred thirty-eight subjects with migraine were recruited.
      One hundred seven subjects completed a baseline and a 24-hour postmigraine
      quality of life questionnaire, along with a migraine diary for recording headache
      severity, activity limitation, associated symptoms, duration of headache, and use
      of migraine medication. All five migraine quality of life questionnaire domains
      showed good internal consistency (Cronbach's alpha, 0.74-0.95). The strongest
      correlations were seen between activity limitation and associated symptoms and
      the migraine quality of life questionnaire work, social, and energy domains.
      Significant differences in mean questionnaire scores between subjects were found
      with frequency of medication use, global change in symptoms, headache duration,
      and severity. All five domains showed significant responses within subjects from
      a migraine-free period to an acute migraine period (P < 0.0001). In summary, the
      migraine quality of life questionnaire showed good internal consistency,
      construct and discriminant validity, and responsiveness to acute migraine
      attacks.

PMID- 7635719
TI  - Exteroceptive suppression of temporalis muscle activity: a blind study of tension
      type headache, migraine, and cervicogenic headache.
AB  - Exteroceptive suppression of temporalis muscle activity (ES2 duration) has been
      reported to be reduced in chronic tension-type headache in previous open studies
      (with varying stimulus and analysis methods). We studied ES2 duration and latency
      in 11 patients with chronic tension-type headache, 10 patients with cervicogenic
      headache, 11 migraine patients, and 9 headache-free control subjects. The
      investigator was blinded as to the diagnostic category. Electrical stimuli of 0.5
      ms duration and at least three times sensory threshold (median 9.6 mA) were used.
      ES2 was obtained in all but one (control) subject and the control ES2 duration
      mean was 33.5 (SD 8.5) ms (80% EMG amplitude reduction criterion). Mean ES2
      duration differences were not found between the four groups. None of the headache
      patients had ES2 durations below the control group range. ES2 duration tended to
      decrease with increasing duration of headache history. Consistent asymmetries of
      ES2 latency and duration were not found among patients with (unilateral)
      cervicogenic headache. Thus, the role of ES2 in headache diagnosis still seems to
      be unsettled.

PMID- 7635722
TI  - Relationships between food, wine, and beer-precipitated migrainous headaches.
AB  - Five hundred seventy-seven consecutive patients attending the Princess Margaret
      Migraine Clinic from 1989 to 1991 have been questioned about dietary precipitants
      of their headaches. Four hundred twenty-nine patients had migraine, of which
      16.5% reported that headaches could be precipitated by cheese or chocolate, and
      nearly always both. Of the migraine patients, 18.4% reported sensitivity to all
      alcoholic drinks, while another 11.8% were sensitive to red wine but not to white
      wine; 28% of the migrainous patients reported that beer would precipitate
      headaches. There was a definite statistical association between sensitivity to
      cheese/chocolate and to red wine (P < 0.001) and also to beer (P < 0.001), but
      none between diet sensitivity and sensitivity to alcoholic drinks in general.
      None of 40 patients with tension headache (diagnosed by International Headache
      Society criteria) reported sensitivity to foods, and only one was sensitive to
      alcoholic drinks. The prevalence of sensitivity among 46 patients with some
      migrainous features was intermediate between the migraine and tension headache
      categories. It is concluded that cheese/chocolate and red wine sensitivity, in
      particular, have closely related mechanisms, in some way related more to migraine
      than to more chronic tension-type headache, while quite separate mechanisms play
      a major role in sensitivity to alcoholic drinks in general.

PMID- 7635720
TI  - Respiratory studies in SUNCT syndrome.
AB  - Seven SUNCT patients (six men, one woman) took part in this study. In four
      patients, respiratory variables were compared during and outside attacks. In five
      patients, peripheral chemosensitivity was tested and compared with a control
      group matched with respect to age, sex, and smoking habits. The results indicate
      that SUNCT patients hyperventilate during attacks. Moreover, they appear to
      hyperventilate slightly under basal conditions. The tests for peripheral
      chemoreceptor activity indicated no differences between the SUNCT and the control
      groups except for one variable, namely the mean ventilatory response to a single
      breath of 13% CO2. It is possible that this indicates a blunted response of the
      peripheral chemoreceptors. On the other hand, it may also represent a chance
      finding, since none of the other results presented suggested such a conclusion,
      and the size of the test group was very small. The results do not indicate that a
      reduction in oxygen saturation can trigger SUNCT since low levels of oxygen
      saturation were only rarely accompanied by SUNCT, whereas many attacks were not
      associated with any appreciable lowering in arterial oxygen saturation.

PMID- 7635721
TI  - A comparative study of selected patient variables as risk factors in
      hospitalization for chronic headache.
AB  - Patients seeking relief for chronic headache at specialized headache treatment
      centers are offered a multidisciplinary approach to treating their disorder.
      Neurologists, who specialize in headache, offer both inhospital and outpatient
      treatment programs. Clinicians and researchers experienced in headache disorders
      have advocated inpatient treatment for certain patients. Hospital programs
      address such issues as elevated anxiety and depression levels, overuse of
      analgesics, and related factors. This study was undertaken to investigate those
      differences, long observed by clinicians, between patients assigned to inpatient
      or outpatient care or to both. In view of the ever-tightening purse strings of
      third-party payers, the results may aid in delineating some of the forthcoming
      practice guidelines for dealing with headache sufferers. This study suggests: (a)
      significant differences do exist between the groups, (b) hospitalized patients
      may indeed require more complex interventions than those managed with outpatient
      care, and (c) documenting some of the etiologic factors that predict
      hospitalization may help alert providers at the front end and preclude some of
      the current need for hospital care.

PMID- 7635723
TI  - Changes in cerebral blood flow velocity associated with biofeedback-assisted
      relaxation treatment of migraine headaches are specific for the middle cerebral
      artery.
AB  - Twenty-five patients with diagnosed migraine headaches were randomly assigned to
      a biofeedback-assisted relaxation therapy group or to a group who relaxed on
      their own. This study confirmed that the biofeedback trained group significantly
      decreased pain and medication more than the self-relax group. The best responders
      were those with the more elevated initial cerebral blood flow values and the
      changes in cerebral blood flow were specific for the middle cerebral artery.

PMID- 7635725
TI  - Hemiplegic migraine with CSF abnormalities.
AB  - A 30-year-old woman with hemiplegic migraine and an elevated CSF protein level
      with considerable pleocytosis is described. Fourteen other cases of hemiplegic
      migraine with cerebrospinal fluid abnormalities reported in the literature are
      reviewed.

PMID- 7635724
TI  - CPH and hemicrania continua: requirements of high indomethacin dosages--an
      ominous sign?
AB  - Two female patients, one with chronic paroxysmal hemicrania and one with
      hemicrania continua, had a continuously high requirement of indomethacin, ie, >
      or = 225 mg per day, for 4 and 7 years, respectively. In the hemicrania continua
      patient, a right (symptomatic side) C7 root affection due to disc herniation was
      demonstrated. Removal of the disc relieved the arm pain completely, and reduced
      the head pain and indomethacin requirement considerably initially. The other
      patient suffered from the unremitting form of chronic paroxysmal hemicrania with
      right-sided attacks from the age of 16. Indomethacin, 200 to 250 mg per day
      generally kept the headache at bay, but during exacerbations, especially during
      menstrual periods, the dosage transitorily had to be increased to 250 to 350 mg
      per day. A CT scan with contrast at aged 18 (1987) was negative. In 1992, she
      started having new symptoms, including numbness on the ipsilateral side of the
      face and arm and difficulty swallowing. An MR scan showed a meningioma
      originating in the roof of the cavernous sinus on the symptomatic side. The
      meningioma was surgically removed. The postoperative indomethacin requirement was
      reduced, but only transiently. Patients with chronic paroxysmal hemicrania (CPH)
      and hemicrania continua (HC) with a continuously high indomethacin requirement
      may have grave additional disorders and should consequently be followed closely.

PMID- 7635726
TI  - Overview and dosimetry of the Hanford Americium accident case.
AB  - Postmortem examinations of selected tissues from an individual who received a
      massive internal exposure to 241Am and succumbed to pre-existing cardiovascular
      disease 11 y later are summarized. Significant findings include acellularity of
      the marrow, marked peritrabecular fibrosis, and a lack of bone surface
      remodeling, confirmed by bone-surface alpha-spectrometry; tissue concentrations
      of 241Am that indicate bone and liver as the primary deposition sites, in general
      agreement with the new ICRP model, but not with the older models; a distribution
      of 241Am in soft tissues in general agreement with that observed in animals; and
      the absence of any other gross or microscopic pathological findings attributable
      to the exposure. Cumulative absorbed doses to the bone, bone surface, liver, and
      lung were 18, 520, 8, and 1.6 Gy, respectively. The probability of not observing
      a fatal cancer based on BEIR-IV risk factors for these absorbed doses was 12%.

PMID- 7635727
TI  - Postmortem tissue contents of 241Am in a person with a massive acute exposure.
AB  - 241Am was determined radiochemically in the tissues of USTUR Case 246, a 76-y-old
      man who died of cardiovascular disease 11 y after massive percutaneous exposure
      following a chemical explosion in a glove box. This worker was treated
      extensively with a chelation drug, DTPA, for over 4 y after exposure. The
      estimated 241Am deposition at the time of death was 540 kBq, of which 90% was in
      the skeleton, 5.1% in the liver, and 3.5% in muscle and fat. Among the soft
      tissues, the highest concentrations were observed in liver (22 Bq g-1), certain
      cartilaginous structures such as the larynx (15 Bq g-1) and the red marrow (9.7
      Bq g-1), as compared with the mean soft tissue concentration of approximately 1
      Bq g-1. Concentration in muscle was approximately that of the soft tissue
      average, while concentrations in the pancreas, a hilar lymph node and fat were
      less than the average. Concentrations in bone ash were inversely related to the
      ratio of ash weight to wet weight, a surrogate for bone volume-to-surface ratio.
      The distribution of activity in this case is reasonably consistent with that
      observed in another human case, when allowance is made for chelation therapy, and
      also tends to support more recent models of 241Am metabolism.

PMID- 7635728
TI  - Bone surface concentrations and dose rates 11 years after massive accidental
      exposure to 241Am.
AB  - Alpha-particle spectrograms of bone samples from USTUR Case 246 were analyzed to
      determine the depth in tissue from which the 241Am alpha-particles were emitted.
      In four samples of bone, the lack of energy straggling in the alpha spectra
      indicated that essentially all the 241Am was deposited directly on the exposed
      bone surface, and none had been translocated to within bone volume. These
      findings agree well with the results of autoradiographic examination of bone
      samples from the same case, but are in marked contrast to findings on another
      case (USTUR Case 102) who had been exposed to a much smaller amount of 241Am at a
      younger age and survived approximately twice as long after the exposure. It is
      problematical whether the lack of 241Am redistribution, and therefore the implied
      absence of bone remodeling, in Case 246 was due to his advanced age at exposure
      or to a deterministic effect of alpha-irradiation on bone metabolism, but the
      observation of radiation effects on bone metabolism in former radium workers
      supports the latter.

PMID- 7635730
TI  - Deterministic effects of 241Am exposure in the Hanford Americium accident case.
AB  - Lifetime follow-up of USTUR Case 246 demonstrated the lack of severe biological
      effects resulting from his exposure to 241Am. Deterministic effects observed were
      limited to hematological changes, including lymphopenia and thrombocytopenia.
      These hematological changes were consistent with those observed in experimental
      animals following actinide exposure. Cataracts were removed from the left and
      right eyes at 547 and 1,030 d after the accident, respectively, but were
      considered to be trauma-induced rather than radiation-induced. No abnormal
      findings were reported from gross or histological examinations of tissue samples
      removed at autopsy, other than those resulting from the subject's preexisting
      cardiovascular disease.

PMID- 7635731
TI  - An analysis of the equivalent dose calculation for the remainder tissues.
AB  - In the 1990 Recommendations of the International Commission on Radiological
      Protection, the risk-weighted quantity "effective dose equivalent" was replaced
      by a similar quantity, "effective dose." Among other alterations, the selection
      of the organs and tissues contributing to the risk-weighted quantity and their
      respective weighting factors were changed, including a modified definition of the
      so-called "remainder." Close consideration of this latter definition shows that
      it causes certain ambiguities and unexpected effects which are dealt with in the
      following. For several geometries of external photon irradiation, the numerical
      differences of two possible methods of evaluating the remainder dose from the
      doses to ten single organs, namely as arithmetic mean or as mass weighted
      average, are assessed. It is shown that deviation from these averaging
      procedures, as prescribed for those cases where a remainder organ receives a
      higher dose than an organ with a specified weighting factor, causes
      discontinuities in the energy dependence of the remainder dose and, consequently,
      also non-additivity of this quantity. These problems are discussed, and it is
      shown that, although the numerical consequences for the calculation of the
      effective dose are small, this unsatisfactory situation needs clarification. One
      approach might be to abolish some of the ICRP guidance relating to the
      appropriate tissue weighting factors for the remainder tissues and organs and to
      make other guidance more precise.

PMID- 7635729
TI  - Histopathology and 241Am microdistribution in skeletal USTER Case 246.
AB  - Histopathology and qualitative autoradiography studies were undertaken on bone
      removed at autopsy from USTUR Case 246. The histopathology examination revealed
      extensive bone marrow peritrabecular fibrosis and decreased cellularity in most
      samples. In addition, histological indicators suggest that bone cell turnover was
      suppressed at most sites, although turnover was found to be essentially normal in
      a vertebral body sample. The autoradiographic studies showed that bone turnover
      that had occurred resulted in the redistribution of americium within bone.
      However, surface deposits of americium remained conspicuous at many sites,
      particularly those with low bone growth activity. A few percent of the americium
      was present in the bone marrow. The dosimetric and toxicology findings indicate
      that current assumptions about the metabolic behavior of bone-seeking
      radionuclides are likely to be unrealistically simplistic.

PMID- 7635732
TI  - The influence of radiation and nonradiation factors on the lung cancer incidence
      among the workers of the nuclear enterprise Mayak.
AB  - For the estimation of radiation lung cancer risk for a human being it is
      important to take into account different etiological factors because of the
      polyetiology of this disease. This work was the aim of a retrospective
      investigation ("case-control") of 500 workers of a nuclear enterprise that had
      been gamma-irradiated in a wide dose range and had had exposure to airborne
      239Pu. One hundred sixty-two persons contracted lung cancer (morbidity), and 338
      persons that had not fallen ill served as pair control. Eleven potential risk
      factors were evaluated using a logistic regression model, five insignificant
      factors were excluded, and the remaining factors were arranged (by odds ratio) in
      decreasing order: smoking > plutonium pneumosclerosis > plutonium incorporation
      in body > chronic obstructive pulmonary diseases (COPD) > decrease of body mass >
      external gamma-irradiation. The percentage of histologically confirmed
      adenocarcinoma among the nuclear enterprise workers was 74%, which is
      significantly higher than 33% among the population that did not work at the
      enterprise, particularly in the case of high (more than 11 kBq) plutonium
      incorporation by the nuclear workers. The localization of tumors in this cohort
      is more frequently in the lower and middle lung lobes and at the periphery. Each
      of the histological types of lung cancer has manifested a different degree of
      correlation with particular factors. The adenocarcinoma has the most frequent
      correlation with the radiation factors; the odds ratio for plutonium
      incorporation and plutonium pneumosclerosis is 2.9 (95% CI = 1.0-8.4); for
      external gamma-irradiation the odds ratio is 1.9 (0.99-3.5); the odds ratio for
      smoking is 4.3 (1.9-9.9). The squamous-cell carcinoma has the highest correlation
      with non-occupational factors: with smoking the OR is 6.8 (1.2-38.7), with the
      chronic obstructive pulmonary diseases the odds ratio is 3.9 (1.8-8.4), and with
      body mass decrease the odds ratio is 2.1 (0.94-4.6); odds ratio for plutonium
      incorporation is 4.2 (1.4-12.8). The small-cell carcinoma has correlation with
      body mass decrease [odds ratio = 2.9 (1.2-7.6)] and high level of smoking
      [smoking index > 500; odds ratio = 3.5 (1.4-8.9)]. The portion of the
      occupational cancers among the workers of the nuclear enterprise, evaluated on
      the base of attributive risk, is 26%, with 57% for adenocarcinoma, 9% for
      squamous-cell carcinoma, and 8% for small-cell carcinoma. The investigation is
      continued to assess the dose-effect and factors interactions.

PMID- 7635734
TI  - Effects of elastic and inelastic scattering in giving electrons tortuous paths in
      matter.
AB  - Heavy charged particles travel in essentially straight lines in matter, while
      electrons travel in tortuous paths. Frequent multiple elastic Coulomb scattering
      by atomic nuclei is often cited as the reason for this electron behavior. Heavy
      charged particles also undergo multiple Coulomb scattering. However, because they
      are massive, significant deflections occur only in rare, close encounters with
      nuclei. In contrast to heavy particles, the inelastic interaction of an electron
      with an atomic electron represents a collision with a particle of equal mass. In
      principle, therefore, repeated inelastic scattering of an electron can also
      produce large-angle deflections and thus contribute to the tortuous nature of an
      electron's track. To investigate the relative importance of elastic and inelastic
      scattering on determining the appearance of electron tracks, detailed Monte Carlo
      transport computations have been carried out for monoenergetic pencil beams of
      electrons normally incident on a water slab with initial energies from 1 keV to 1
      MeV. The calculations have been performed with deflections due to (1) inelastic
      scattering only, (2) elastic scattering only, and (3) both types of scattering.
      Results are presented to show the spreading of the pencil beams with depth in the
      slab, the transmission through slabs of different thicknesses, and back
      scattering from the slab. The results show that elastic nuclear scattering is
      indeed the principal physical process that causes electron paths to be tortuous;
      however, the smaller effect of inelastic electronic scattering is far from
      negligible.

PMID- 7635733
TI  - The influence of a subslab gravel layer and open area on soil-gas and radon entry
      into two experimental basements.
AB  - Measurements of steady-state soil-gas and 222Rn entry rates into two room-sized
      experimental basement structures were made for a range of structure
      depressurizations (0-40 Pa) and open floor areas (0-165 x 10(-4) m2). The
      structures are identical except that in one the floor slab lies directly on
      native soil whereas in the other the slab lies on a high-permeability gravel
      layer. The subslab gravel layer greatly enhances the soil-gas and radon entry
      rate into the structure. The radon entry rate into the structure with the subslab
      gravel layer is four times greater than the entry rate into the structure without
      the gravel layer with an open floor area of 165 x 10(-4) m2; however the ratio
      increases to 30 for an open floor area of 5.0 x 10(-4) m2. The relationship
      between open area and soil-gas entry rate is complex. It depends on both the
      amount and distribution of the open area as well as the permeability of the soil
      near the opening. The entry rate into the experimental structures is largely
      determined by the presence or absence of a subslab gravel layer. Therefore open
      area is a poor indicator of radon and soil-gas entry into the structures. The
      extension of the soil-gas pressure field created by structure depressurization is
      a good measure of the radon entry. The measured normalized radon entry rate into
      both structures has the same linear relationship with the average subslab
      pressure coupling is an estimate of the extension of the soil-gas pressure field.
      A three-dimensional finite-difference model correctly predicts the effect of a
      subslab gravel layer and different open area configurations on radon and soil-gas
      entry rate; however, the model underpredicts the absolute entry rate into each
      structure by a factor of 1.5.

PMID- 7635735
TI  - Mammary tumor occurrence in beagles given 239Pu.
AB  - Comparison of 120 young adult female beagles given 0.026 to 106 kBq 239Pu kg-1 by
      intravenous injection and 63 comparable female control beagles showed that there
      were no significant differences in the risk of mammary tumor appearance between
      the two groups. This was the case for benign tumors only, for malignant tumors
      only, and for both malignant and benign tumors considered together. For malignant
      tumors the observed number was 73 as compared with 69 expected; for benign
      tumors, there were 131 observed and 126 expected; for all tumors (separate
      analysis, not just the addition of malignant plus benign), there were 199
      observed and 199 expected. Chi-square analysis indicated that the p values for
      all these comparisons were > 0.05. There were 45 controls (71.4%) with any tumor
      vs. 67 dogs (55.8%) given Pu (95% C. I. = 46.9% to 86.2%). No significant
      differences could be established (Kaplan-Meier analysis) between these two groups
      for survival age at diagnosis of the first mammary tumor, 11.75 +/- 0.30 y for
      dogs given Pu vs. 11.90 +/- 0.36 y for controls. We reported previously that
      differences in mammary cancer occurrence had been identified between this same
      group of control dogs and 57 female beagles given 226Ra as young adults. The
      present study appears to support the earlier conclusion that something other than
      alpha irradiation of the skeleton (both 226Ra and 239Pu deposit in bone) seems to
      affect the appearance of mammary cancers, since internally deposited 226Ra does
      appear to induce these malignancies, possibly from initial deposition in mammary
      tissue of the parent radionuclide or the subsequent concentration in sensitive
      tissue of its radioactive progeny, 22Rn or isotopes of polonium, lead, and
      bismuth, which are absent in the case of 239Pu.

PMID- 7635736
TI  - Simulation of the upper gastrointestinal fluoroscopic examination for calculation
      of absorbed dose in tissue.
AB  - In order to simulate the upper gastrointestinal fluoroscopic examination,
      modifications were made to the Monte Carlo radiation-transport code that uses the
      anthropomorphic, mathematical reference phantoms ADAM and EVA. A set of discrete
      x-ray field projections of the principal anatomy of clinical interest has been
      previously defined. This note describes the new features incorporated in the
      simulations--divergent beams in oblique irradiation geometries, an esophagus and
      a duodenum, a double contrast medium consisting of a BaSO4-H2O mixture and air in
      the esophagus, stomach, and duodenum, and clinically representative beam
      qualities. The absorbed doses in tissues per unit entrance exposure (free-in-air)
      computed with the modified code appeared in Department of Health and Human
      Services Publication FDA 92-8282, Handbook of Selected Tissue Doses for the Upper
      Gastrointestinal Fluoroscopic Examination. A minor correction is described for
      the previously reported results for the esophagus.

PMID- 7635737
TI  - Silicosis, radon, and lung cancer risk in Ontario miners.
AB  - The presence of radiographic silicosis was assessed as a risk factor for lung
      cancer in a cohort and case-control study of miners in the Ontario Silicosis
      Surveillance Database. Subjects were 328 miners with silicosis matched on age to
      970 miners with normal radiographs. In a cancer incidence follow-up, there was a
      significant excess of lung cancer among miners with silicosis (Standardized
      Incidence Ratio 2.55; 95% Confidence Interval 1.43-8.28). Miners with normal
      radiographs had lung cancer incidence about the same as the Ontario average
      (Standardized Incidence Ratio 0.90; 95% Confidence Interval 0.51-1.47). In a
      matched case-control analysis of lung cancer, cumulative radon exposure was
      associated with lung cancer risk (increase in odds ratio 0.4% per WLM; 95%
      Confidence Interval -0.3% to 1.1%). When the presence of silicosis was added to
      the model, silicosis was a highly significant risk factor for lung cancer (Odds
      Ratio 6.99 95% Confidence Interval 1.91-25) and the risk factor for radon was
      diminished (increase in Odds Ratio -0.5% per WLM; 95% confidence Interval -1.4%
      to 0.4%). This finding suggests that additional study is warranted before
      concluding that radon risk factors derived from mining populations do not need to
      be modified for application to the general population.

PMID- 7635738
TI  - Studies on the biological half-lives of three important radionuclides released in
      nuclear power reactor operations.
AB  - The four important parameters involved in the calculation of internal radiation
      dose to the human body, per unit intake of a radionuclide are 1) weight and size
      of the body organs; 2) the biological (retention) half-life of the radionuclide;
      3) radiation weighting factors for the type of radiations emanating from the
      radionuclide; and 4) the organ weighting factors for the organs being irradiated
      (target organs). Whereas, for a particular radionuclide, the radiation weighting
      factor and the organ weighting factors may remain constant for all humans, the
      other two parameters, namely, the organ weights and biological half-life, are
      population specific and may differ from one population group to another. For a
      realistic dose estimation, the population specific data on organ weights and
      biological half-lives for various radionuclides therefore, are needed.

PMID- 7635739
TI  - Determination of waterborne 222Rn concentrations using AC canisters.
AB  - A method for measuring 222Rn concentration in water using charcoal canisters is
      presented. 222Rn is transferred within a few minutes from water contained in a
      0.720 L bottle to a charcoal canister using a portable degassing unit. In the
      laboratory, gamma counting is performed at least 10 h after sampling to determine
      waterborne 222Rn concentration. The results obtained with charcoal canisters are
      compared to measurements made with Marinelli beakers calibrated in a comparison
      with liquid scintillation counting. The efficiency of transferring dissolved
      222Rn in water to activated charcoal is 99%, based on measurements made using
      Marinelli beakers. The lower limit of detection at the 95% confidence level is
      approximately 1 kBq m-3 for a 15 min gamma count. The system was used to measure
      radon concentration in mineral groundwater near Rome.

PMID- 7635740
TI  - Evaluation of soil radioactivities using pedologically based sampling techniques.
AB  - A new type of soil sampling protocol is suggested which has applicability to
      surveys of environmental radioactivity. Often there is a higher concentration of
      radionuclides in the lower B horizon than in the upper A horizon of well-drained,
      well-developed soils. It is recommended that soils be sampled pedologically,
      i.e., by soil horizon, rather than incrementally in depth. An example is given
      from a site in northern Louisiana where surface and/or the classical 15 cm ("six
      inch") deep sampling could lead to erroneous conclusions regarding anthropogenic
      contamination.

PMID- 7635742
TI  - Radiation design and control features of a hospital room for a low dose rate
      remote afterloading unit.
AB  - We have renovated, and used for four years, a small 3.4 m x 4.3 m conventional
      patient second floor hospital room to accommodate a low dose rate remote
      afterloading unit containing 13 GBq (0.35 Ci) of 137Cs. Supplemental room
      shielding consists of a power assisted door (536 kg, 1.7 cm thickness of lead),
      1.3 cm lead wall shielding at selected wall locations and on a projector shield
      beneath the bed, and 0.6 cm of lead over the floor above. Radiation control
      features consisted of a room interior radiation detector independent of the
      remote afterloading unit, a redundant patient/nurse communication system, a
      remote control system, a door interlock system to insert and retract the
      radioactive pellets, and a visible and audible status indicator system located at
      a nearby nurses' work station. Renovation costs (in 1990 dollars) were $383 per
      square foot; total project costs were $187,000. Nursing personnel radiation
      exposure was reduced from about 6 microSv (mg Ra eq)-1 (0.6 mrem (mg Ra eq)-1) to
      about 0.7 microSv (mg Ra eq)-1 (0.07 mrem (mg Ra eq)-1, almost a tenfold
      reduction.

PMID- 7635744
TI  - Incorporating the Agency for Healthcare Policy and Research: guidelines into a
      home health agency's performance improvement plan.

PMID- 7635743
TI  - Comments on dose measurements for 89Sr chloride injections.

PMID- 7635741
TI  - Ratios of transfer coefficients for radiocesium transport in ruminants.
AB  - A corollary of the multiple-compartment model for the transport of trace elements
      through animals was tested for cows, goats, and sheep. According to this
      corollary, for a given body "compartment" k of the animal (soft tissue, lung,
      liver, etc.), the ratio a(k) = f(k)/f(blood) of the transfer coefficients f,
      should exhibit similar values for physiologically similar animals. In order to
      verify this prediction, two experiments were performed at the Agricultural
      Research Station of Ioannina and at the facilities of Ria Pripyat in Pripyat,
      Ukraine. Eight animals in the first experiment and eighteen in the second were
      housed in individual pens and were artificially contaminated with a constant
      daily dose of radiocesium until equilibrium was reached. The animals were then
      sacrificed and transfer coefficients f(k) to twelve body "compartments" k were
      measured. These data were used to calculate the ratios a(k). The results were in
      accordance with predictions of the model and average values of a(k) were
      extracted for ruminants. It is concluded that these values may be employed for
      the prediction of animal contamination in any body compartment through the
      measurement of blood samples.

PMID- 7635745
TI  - Psychiatric home care: an introduction.
AB  - Healthcare has undergone many changes in the past 5 years. Hospitalization has
      become extremely expensive to the consumer and the payor. Alternative healthcare
      services are being considered and used, with the emphasis on cost containment and
      cost and clinical effectiveness. Psychiatric home care is clinically effective
      and less costly.

PMID- 7635746
TI  - Bay Area Health Care Psychiatric Home Care Model.
AB  - This article describes the Bay Area Health Care Psychiatric Home Care Model. The
      symbol of a home is used to define the components of the model. The foundation of
      the house is a moral/spiritual one. The walls of the home are made up of
      assessment skills and relationship building. The second floor of the psychiatric
      home care model, supported by the walls of assessment and relationship, are the
      issues surrounding medications. The two sides of the roof of the psychiatric home
      care model are made up of teaching/psychotherapeutic interventions and case
      management. This model is comprehensive, and directed to caring, stabilizing, and
      maximizing potential.

PMID- 7635747
TI  - The effects of uncertainty in families with children who are chronically ill.
AB  - This study examined the experiences, stresses, support networks, and needs of
      four families with chronically ill children receiving home care. Chronic
      uncertainty appeared to be the major psychosocial stressor confronting each
      family. Parents experienced uncertainty when dealing with the child's illness,
      treatments, other family members, and healthcare professionals. Home care nurses
      had a great impact on minimizing the burden of uncertainty by providing
      consistent support and understanding, and normalizing the home environment.

PMID- 7635748
TI  - Balancing the 'heart' of patient care.
AB  - Home health nurses are in a unique position to facilitate understanding of the
      patient's psychosocial context. As opposed to the practice of minimizing or
      separating this aspect of care, this article emphasizes the importance of a
      collaborative and integrative treatment model.

PMID- 7635749
TI  - Coping with chronic illness.
AB  - Families suffer in many ways when a member is stricken with chronic illness.
      Nurses frequently feel a sense of frustration when working with the chronically
      ill because cure is not possible. The author reviews the goals of care and coping
      tasks common to the chronically ill. Family coping styles are reviewed with
      suggestions for effective nurse behaviors with each style.

PMID- 7635750
TI  - Coping with nursing home placement of a parent.
AB  - This article describes an educational program that can be used by health
      professionals to help family members work through emotional distress associated
      with nursing home placement. The program of preplacement education presented here
      does not address the issues and stressors surrounding the decision-making
      process. The Coping with Nursing Home Placement program is designed to be used
      after the decision has been made to place a parent in the nursing home. Home
      health nurses know only too well that once a family makes the decision to seek
      placement, the wait for a bed can be lengthy.

PMID- 7635752
TI  - Psychiatric home healthcare nursing.

PMID- 7635751
TI  - Continence consultation for the rural homebound.
AB  - Because an estimated 10 million Americans have urinary incontinence, home care
      continence services are in demand. In March 1992, the Agency on Health Care
      Policy and Research recommended behavioral therapy as a first step in treatment
      options for urinary incontinence. Nurses are best prepared to meet the challenges
      of providing behavioral therapy to people who are incontinent and are being cared
      for in their homes. This article describes the development of a nursing practice
      that provides assessment and treatment of urinary incontinence to people who are
      homebound in rural Northern Vermont.

PMID- 7635753
TI  - Hospice care can obviate the need for suicide.

PMID- 7635754
TI  - Community health nursing in international disasters.

PMID- 7635755
TI  - The bedbound home care client.

PMID- 7635756
TI  - The Medicare Home Health Benefit.

PMID- 7635757
TI  - Nursing research in HIV/AIDS home care, Part 2: Results and implications.
AB  - This study categorized the problems of clients with human immunodeficiency
      syndrome/acquired immune deficiency syndrome (HIV/AIDS), identified on admission
      to home care, into nursing diagnoses. The study followed a descriptive
      retrospective record review of adult men and women (n = 244) admitted to a
      certified home health care agency in New York City. When all problems were
      clustered into nursing diagnoses, the principle diagnosis in more than 70% of the
      sample were impaired home maintenance, high risk for ineffective individual
      coping, altered nutrition:less than body requirements, feeding self-care deficit,
      and fatigue. The results indicate that the home healthcare needs of persons with
      HIV/AIDS are multifaceted in nature and extend beyond the signs and symptoms of
      advancing disease. Nursing diagnoses serve as a basis for capturing all data that
      contribute to client problems and are the focus of planning nursing care in the
      home.

PMID- 7635758
TI  - The role of lectins in plant defence.
AB  - Recent progress in the search for the physiological role of plant lectins
      supports the idea that some of these proteins are involved in the defence
      mechanisms of the plant. To place the evidence in favour of such a defensive role
      in a broad perspective, a short overview is given of the most important plant
      pathogens and predators. In addition, the solutions that plants have developed to
      resist the continuous threat of a hostile environment are briefly discussed in
      relation to the protective role of proteins in general. The presumed involvement
      of plant lectins in defence mechanisms is first inferred from an analysis of the
      biochemical, physiological, cellular biological and molecular biological
      properties of plant lectins. Subsequently, the available experimental evidence
      for the involvement of lectins in the plant's defence against viruses, bacteria,
      fungi and herbivorous invertebrates and vertebrates is discussed in some detail.
      Since the defensive role of plant lectins is determined largely by their ability
      to recognize and bind foreign glycans, a brief discussion is given of how the
      basically protective properties of these proteins can be exploited for
      histochemical applications in biological and biomedical research.

PMID- 7635759
TI  - Ultrastructural examination of B-50(GAP-43) immunoreactivity in rat jejunal
      villi.
AB  - The lamina propria of rat jejunum is densely innervated with nerve fibres
      extending to the tips of the villi. A large number of these nerve fibres were
      previously shown to be B-50-immunoreactive at the light microscope level, whereas
      neurofilament immunoreactivity was found to be sparse in the mucosa. In this
      study we used immunoelectron microscopy to determine what proportion of nerve
      fibres in the lamina propria express B-50. Jejuna from male Lewis rats were
      immunolabelled for B-50 and neurofilament proteins. For electron microscopy,
      postembedding immunogold-silver techniques and LR White embedded tissues were
      used. Light microscopical immunostaining was performed by the streptavidin-biotin
      peroxidase technique on deparaffinized tissue sections. We found that all
      ultrastructurally identifiable nerve profiles in jejunum were B-50
      immunoreactive. Immunoelectron microscopy for neurofilament proteins failed to
      label fibres in the villi, whereas myelinated nerves in tongue sections processed
      in parallel (positive controls) were strongly neurofilament-protein
      immunoreactive. The dominant B-50-positive and neurofilament-protein-negative
      phenotype supports the hypothesis of ongoing modelling or plasticity of
      intestinal mucosal nerves.

PMID- 7635760
TI  - Enzymatic detection systems for non-isotopic in situ hybridization using
      biotinylated cDNA probes.
AB  - The feasibility of various non-isotopic enzymatic detection systems was tested
      for in situ hybridization using biotin-labelled, nick-translated cDNA probes. For
      this purpose, we isolated and prepared cDNA restriction fragments encoding the
      proteolytic cysteine proteinase cathepsin L and analysed Kirsten murine sarcoma
      virus-transformed BALB/3T3 cells, which have been shown to express high amounts
      of cytoplasmic RNA of this ras oncogene-induced proteinase. When compared on a
      semiquantitative basis, colorimetric non-isotopic detection of cDNA hybrids with
      avidin-biotin-peroxidase conjugates visualized by silver intensification of the
      nickel-diaminobenzidine end-product was superior to that obtained with avidin
      biotin-alkaline phosphatase using different substrates for development. When the
      peroxidase staining technique was applied for RNA detection, it was found that
      overnight incubation in methanol containing hydrogen peroxide followed by
      deproteination with HCl was the most effective method for inhibition of
      endogenous peroxidase activity. For DNA detection, non-specific nucleic staining
      was completely abolished when heat treatment (100 degrees C) of the cell
      specimens was performed prior to hybridization.

PMID- 7635761
TI  - Distribution of calcineurin A isoenzyme mRNAs in rat thymus and kidney.
AB  - The distribution of the mRNAs encoding the different isoforms of the catalytic
      subunit (A subunit) of calcineurin has been investigated in rat thymus and kidney
      using in situ hybridization histochemistry with specific antisense
      oligonucleotide probes. In the thymus, the mRNAs of the A beta isoforms were the
      predominant transcripts and showed very intense hybridization signals in the
      cortical areas. The A alpha mRNAs were expressed at low levels. A beta 2 mRNA was
      expressed at higher levels than A beta 3 mRNA, but no difference could be
      detected between the expression levels of A alpha 1 and A alpha 2. In the kidney,
      highest calcineurin A mRNA hybridization signals were found in the medulla.
      Signal intensities of A alpha mRNAs were comparable to those of A beta mRNAs. A
      alpha 1 mRNA level was extremely weak, and A beta 2 mRNA expression was slightly
      higher than A beta 3 mRNA expression. A tissue-specific distribution pattern of
      the alternatively spliced isoforms of calcineurin A, as suggested by these
      preliminary data from thymus and kidney, may be critical in understanding the
      toxic side-effects associated with the use of the immunosuppressive, calcineurin
      inhibiting compounds cyclosporin A and FK506.

PMID- 7635762
TI  - Binding of bacterial toxins to glycoproteins in the envelopes of rainbow trout
      eggs.
AB  - The ability of the vitelline and fertilization envelopes of rainbow trout eggs to
      trap toxins was investigated using cholera enterotoxin B and staphylococcal
      enterotoxin B in cytochemical or immunocytochemical experiments. Extracts from
      both envelopes were investigated by immunoblot analysis to identify toxin-binding
      proteins after SDS-PAGE. Binding studies of cholera enterotoxin B to vitelline
      envelopes and fertilization envelopes revealed a greater reactive intensity in
      the former. Treatment with neuraminidase enhanced the reactive intensity (or
      deposit) in the vitelline envelope and fertilization envelope outermost layers,
      with more conspicuous reactivity in the former. Cytochemical experiments showed
      that exogenous ganglioside GM1 considerably enhanced cholera enterotoxin B
      binding to vitelline and fertilization envelopes. This enhancement was shown by
      an intense reactivity following the occurrence of new binding sites on the
      vitelline envelope inner surface and the inner wall of the zona radiata, a
      simultaneous extreme reduction in the reactivity of the vitelline envelope
      outermost layer, and a striking increase in reactive products in the
      fertilization envelope outermost layer. The surface region of the vitelline or
      fertilization envelope outermost layer was the binding site for staphylococcal
      enterotoxin B, and neuraminidase treatment caused a considerable reduction of
      reactive products in these areas. Immunoblot analysis of cholera enterotoxin B-
      or staphylococcal enterotoxin B-binding substances in extracts from the vitelline
      envelopes or fertilization envelopes demonstrated that the great majority of the
      binding substances are glycoproteins. The present results suggest that
      glycoproteins constituting the vitelline envelope or fertilization envelope may
      contribute to the protection of the egg itself or the embryo by trapping noxious
      toxins.

PMID- 7635763
TI  - The detection of the mRNAs of procollagen types I, II and III in human fetal
      fingers by in situ hybridization using digoxigenin-labelled oligonucleotide
      probes.
AB  - Messenger RNAs (mRNAs) encoding procollagen alpha 1 type I,alpha 1 type II and
      alpha 1 type III have been localized in paraffin sections of human fetal fingers
      using digoxigenin-labelled synthetic oligonucleotide probes. The probe-mRNA
      hybrids were visualized using an anti-digoxin antibody amplified with sandwich
      techniques. These protocols provided an excellent hybridization signal with
      minimal background noise. The sensitivity of the protocols was nearly equivalent
      to that seen when using isotopic cDNA probes. In human fetal fingers, intense
      hybridization signals for procollagen alpha 1 type I mRNA were detected in the
      osteoblasts and the fibroblasts of periosteum and perichondrium, the tenocytes of
      tendons, fibroblasts of ligaments, the synovial membrane and deeper layers of the
      dermis. In contrast, positive hybridization signals for procollagen alpha 1 type
      II mRNA were visualized in chondrocytes and the cambial layer of perichondrium.
      The signals for procollagen alpha 1 type III mRNA were detected in the
      fibroblasts of the dermis and perichondrium. The probes which have lower melting
      temperatures (Tm) could not detect the corresponding mRNAs.

PMID- 7635764
TI  - Fluorescence of mast cell granules in paraffin sections and cell smears induced
      by an N-quaternary oxazole scintillator.
AB  - The N-quaternized derivative of dimethyl-POPOP (termed Q4) induces a bluish-green
      fluorescent reaction in mast cell granules from paraffin sections and cell
      smears, in addition to a previously described bluish-white fluorescent reaction
      in chromatin DNA. The chromatin reaction was abolished by staining the samples
      either with Mayer's Haematoxylin before Q4 treatment or by Q4 treatment at pH
      1.5. The reaction in mast cell granules was absent after substrate methylation.
      The staining sequence Haematoxylin-Eosin-Q4 also worked well in paraffin
      sections, allowing the observation of the current histological image under bright
      field illumination as well as double-colour emission under fluorescence
      microscopy. The sequence is proposed as a new diagnostic procedure for
      demonstrating mast cell granules.

PMID- 7635765
TI  - Immunocytochemical localization of cyclooxygenase-1 and cyclooxygenase-2 in the
      rat stomach.
AB  - Prostaglandins are considered to play important roles in gastric mucosal
      protection. The rate-limiting enzyme involved in the biosynthesis of
      prostaglandins is cyclooxygenase (COX), also known as prostaglandin H synthase.
      Two forms of COX are known: a constitutively expressed form (COX-1) and a newly
      characterized, inducible form (COX-2). In the present study, the
      immunocytochemical localization of COX-1 and COX-2 was examined in the rat
      gastrointestinal tract. A strong immunoreactivity for COX-1 was localized in the
      mucous neck cells of gastric gland. A weak reactivity for COX-1 was also found in
      the mucous cell types in the cardiac gland and pyloric gland of the stomach as
      well as in the Brunner's gland of duodenum. Ultrastructurally, the
      immunoreactivity was localized to the apical cytoplasm of these cells. On the
      other hand, immunoreactivity for COX-2 was distributed in the surface mucous
      cells in both the fundic and pyloric regions of stomach. These results suggest
      that a subset of mucous cells is the primary site for production of
      prostaglandins in the rat gastrointestinal tract, and that two forms of COX are
      expressed in distinct types of mucous cell.

PMID- 7635766
TI  - Intermediate filaments in the testis of the teleost mosquito fish Gambusia
      affinis holbrooki: a light and electron microscope immunocytochemical study and
      western blotting analysis.
AB  - A light and electron microscope immunocytochemical study and Western blotting
      analysis has been performed on intermediate filaments (vimentin, desmin and
      cytokeratins) in the testis of the teleost fish Gambusia affinis holbrooki. An
      immunoreaction to vimentin was observed in the epithelium of the efferent ducts,
      testicular canal and their surrounding peritubular cells. Positive vimentin
      immunostaining was also observed in the cells located around seminiferous tubules
      (boundary cells), Leydig cells, interstitial fibroblasts, chromatophores, and
      blood vessel endothelial cells. In contrast to mammals, no vimentin
      immunoreactivity was found in the Sertoli cells. Immunoreactivity to desmin was
      weak in the epithelial cells of the efferent ducts and testicular canal and
      intense in the peritubular cells that surrounded these ducts. Desmin
      immunoreactivity was also observed in the seminiferous tubule boundary cells. The
      immunoreactivity was weak in the boundary cells that surrounded germ cell cysts
      containing spermatogonia or spermatocytes and intense in the boundary cells
      around cysts with elongated or mature spermatids. Immunoreactivity towards
      cytokeratins was observed only in testicular blood vessels. Cytokeratin
      immunolabelling was intense in the endothelium and weak in the vascular smooth
      muscle cells. No cytokeratin immunoreactivity was found in the Sertoli cells,
      germ cells, interstitial cells or in the efferent duct epithelium. The absence of
      intermediate filaments in the Sertoli cells, the absence of cytokeratins in the
      epithelium of the sperm excretory ducts, and the presence of desmin filaments in
      these epithelial cells are the most important differences with regards to the
      intermediate filament phenotype in mammalian testes.

PMID- 7635767
TI  - Carcinoma of the uterine cervix. I. Impact of prolongation of overall treatment
      time and timing of brachytherapy on outcome of radiation therapy.
AB  - PURPOSE: Some studies have described decreased pelvic tumor control and survival
      rates in invasive carcinoma of uterine cervix when the overall time in a course
      of definitive irradiation is prolonged. We attempt to confirm or deny these
      observations and evaluate the impact of timing of brachytherapy on outcome. We
      also explore the hypothesis that more extensive tumors technically require
      prolongation of the course of irradiation; thus, decreased tumor control and
      survival in these patients may not necessarily be the result of time/dose factor.
      METHODS AND MATERIALS: Records of 1,224 patients (Stage IB to III) treated with
      definitive irradiation (combination of external beam and two intracavitary
      insertions to deliver doses of 70 to 90 Gy to point A) were reviewed. Follow-up
      was obtained in 97% of the patients (median, 12 years; minimum, 3 years; maximum,
      28 years). The relationship between outcome and overall treatment time and time
      of intracavitary insertions was analyzed in each stage and according to tumor
      size/extent. RESULTS: There was strong correlation between overall treatment time
      (OTT) and tumor stage (< or = 7 weeks: 81% for Stage IB; 74% for Stage IIA; 52%
      for Stage IIB; and 47% for Stage III). Interruptions of therapy accounting for
      prolongation of treatment time occurred in 25-30% of patients, most frequently
      because of holidays and weekends and side effects of therapy. Overall treatment
      time had a major impact on pelvic tumor control in Stages IB, IIA, and IIB; in
      Stage IB 10-year actuarial pelvic failure rates were 7% with OTT < or = 7 weeks,
      22% with 7.1 to 9 weeks, and 36% with > 9 weeks (p < or = 0.01). For Stage IIA
      the corresponding values were 14%, 27%, and 36% (p = 0.08), and in Stage IIB
      pelvic failure rates were 20%, 28%, and 34%, respectively (p = 0.09). In Stage
      III, pelvic failure was 30%, 40%, and 50%, respectively (p = 0.08). There was
      also a strong correlation between OTT and 10-year cause-specific survival (CSS);
      in Stage IB rates were 86% with OTT of < or = 7 weeks, 78% for 7.1 to 9 weeks,
      and 55% for > or = 9 weeks (p < 0.01). The corresponding rates in Stage IIA were
      73%, 41%, and 48% (p < or = 0.01). For patients with Stage IIB, CSS rates were
      72% for OTT < or = 7 weeks, 60% for 7.1 to 9 weeks, and 70% for > 9 weeks (p =
      0.01). Patients with Stage III disease had 45% 10-year CSS when treatment was
      delivered in 9 weeks or less and 36% for longer overall times (p = 0.16). In
      multivariate analysis of patients with Stage IB and IIA, OTT and clinical stage
      were the most important prognostic factors for pelvic tumor control, disease-free
      survival, and CSS. Tumor size was a prognostic factor for CSS. In Stages IIB and
      III, OTT, clinical stage, unilateral or bilateral parametrial invasion, and dose
      to point A were significant prognostic factors for pelvic tumor control, disease
      free survival, and CSS. Prolongation of time had a significant impact on pelvic
      tumor control and CSS regardless of tumor size, except in Stage IB tumors < or =
      3 cm. Regression analysis confirms previous reports that prolongation of OTT
      results in decreased pelvic tumor control rate of 0.85% per day for all patients,
      0.37% per day in Stages IB and IIA, 0.68% per day in Stage IIB, and 0.54% for
      Stage III patients treated with > or = 85 Gy to point A. Performance of all
      intracavitary insertions within 4.5 weeks from initiation of irradiation yielded
      decreased pelvic failure rates in some groups of patients (8.8 vs. 18% in Stage
      IB and IIA tumors < or = 4 cm and 12.3 vs. 35% in Stage IIB) (p < or = 0.01).
      CONCLUSIONS: Prolongation of treatment time in patients with Stage IB, IIA, IIB,
      and III carcinoma of the uterine cervix has a significant impact on pelvic tumor
      control and CSS. The effect of OTT was present regardless of tumor size except in
      Stage IB tumors < or = 3 cm.

PMID- 7635768
TI  - Time course and incidence of late complications in patients treated with
      radiation therapy for FIGO stage IB carcinoma of the uterine cervix.
AB  - PURPOSE: To determine the time course and incidence of late complications from
      radiation therapy in patients treated with radiation for FIGO Stage IB carcinoma
      of the uterine cervix, and to evaluate patient and tumor factors associated with
      an increased probability of treatment complications. METHODS AND MATERIALS: The
      medical records of 1784 patients with FIGO Stage IB cervical carcinoma who were
      treated with initial radiation therapy between 1960 and 1989 were retrospectively
      reviewed. Follow-up was obtained from clinic visits and correspondence with
      patients and their physicians. Treatment complications were graded
      retrospectively. Complication rates were calculated actuarially; patients who
      died of disease or intercurrent illness without experiencing a major complication
      were censored at the time of death. There were 1241, 924, 548, and 274 patients
      followed for more than 5, 10, 15, and 20 years, respectively. RESULTS: Of
      patients treated for Stage IB cervical carcinoma, 7.7% and 9.3% had experienced
      major (> or = Grade 3) complications at 3 and 5 years, respectively. After 5
      years, there was a small but continuous risk of approximately 0.34% per year,
      resulting in an overall actuarial risk of having had major complications of 14.4%
      at 20 years. The risk of developing major urinary tract complications was
      approximately 0.7% per year for the first 3 years of follow-up, decreasing to
      about 0.25% per year for at least 25 years. In contrast, the risk of developing
      rectal complications was about 1% per year during the first 2 years, with a
      subsequent sharp decline to about 0.06% per year between Years 2 and 25. The risk
      of fistula formation was approximately doubled in the 234 patients who underwent
      adjuvant extrafascial hysterectomy (5.3 vs. 2.6% at 20 years; p = 0.04) and in
      the 111 patients who had pretreatment laparotomy (5.2 vs. 2.9%; p = 0.007). The
      risk of developing small bowel obstruction was increased in patients who
      underwent pretreatment laparotomy (14.5 vs. 3.7% at 10 years; p < 0.0001) and in
      patients who weighed < 120 pounds (8.2 vs. 3.6%; p = 0.004), but was not
      increased in patients who underwent adjuvant hysterectomy. A significantly
      greater risk of gastrointestinal complications was observed in black and non
      Hispanic white patients than in Hispanic women (p = 0.01), even though there was
      no difference in the rate of developing urinary tract complications (p = 1.0).
      There was no correlation between the actuarial risk of developing major
      complications and the patients' age at the time of treatment, but the cumulative
      risk was greater for patients who were treated at a young age because these
      patients were more likely to survive to be exposed to a very long period of risk.
      CONCLUSIONS: Using techniques described by Fletcher and Delclos, the risk of
      major complications from aggressive irradiation for Stage IB carcinoma of the
      cervix is low and does not warrant compromises in the intensity of treatment that
      might decrease the high cure rates achieved in such patients. The long time
      course of some late complications also suggests that continued surveillance of
      survivors, by physicians experienced in the diagnosis and management of the
      sequelae of the curative radiation treatment of cervical cancer, is important.

PMID- 7635769
TI  - The adverse effect of treatment prolongation in cervical carcinoma.
AB  - PURPOSE: Proliferation of surviving tumor clonogens during a course of protracted
      radiation therapy may be a cause of local failure in cervical carcinoma. The
      effect of total treatment time was analyzed retrospectively in relation to pelvic
      control and overall survival for squamous cell carcinomas of the uterine cervix.
      METHODS AND MATERIALS: Two hundred and nine patients (Stage IB-IIIB) treated with
      a combination of external beam and low dose rate intracavitary irradiation were
      evaluable for study. Multivariate analysis and Kaplan-Meier statistical methods
      were used to determine the effect of treatment time on pelvic control and
      survival at 5 years. RESULTS: The median treatment duration was 55 days. For all
      stages combined, the 5-year survival and pelvic control rates were significantly
      different with treatment times < 55 days vs. > or = 55 days: 65 and 54% (p =
      0.03), 87 and 72% (p = 0.006), respectively. By stage, a shorter treatment
      duration (i.e., < 55 days vs. > or = 55 days) was significant for 5-year overall
      survival and pelvic control for Stages IB/IIA and III, but not for Stage IIB:
      Stage IB/IIA (81 and 67%, 96 and 84%), Stage III disease (52 and 42%, 76 and 55%)
      and Stage IIB (43 and 50%, 74 and 80%, respectively). Survival decreased 0.6%/day
      and pelvic control decreased 0.7%/day for each additional day of treatment beyond
      55 days for all stages of disease. Additionally, significant late complications
      were not influenced by treatment time. CONCLUSION: These results suggest that
      prolongation of treatment time is associated with decreased local control and
      survival in patients with cervical carcinoma. This is consistent with emerging
      data from other institutions. Therapeutic implications include avoidance of
      unnecessary treatment breaks, the design of fractionation schemes that decrease
      treatment duration, and possibly the use of tumor cytostatic drugs during
      conventional radiation.

PMID- 7635770
TI  - Prognostic factors for local and distant recurrence in stage I and II cervical
      carcinoma.
AB  - PURPOSE: The effects of tumor size, parametrial involvement, and other variables
      on treatment outcome for patients with Federation Internationale de Gynecologie
      et d'Obstetrique (FIGO) Stage I or II cervical carcinoma, as well as treatment
      complications, were analyzed retrospectively. METHODS AND MATERIALS: Records of
      125 patients with FIGO Stage I or II carcinoma of the uterine cervix selected for
      curative radiotherapy between January 1980 and December 1990 were reviewed.
      Twelve patients (9.9%) underwent adjuvant extrafascial hysterectomy and 8
      patients (6.4%) received chemotherapy. Median age was 55 years. Median follow-up
      time was 40 months, and minimum follow-up time was 24 months. The data were
      analyzed for site of first relapse, survival, overall incidence of complications,
      and incidence of grade 4 complications. RESULTS: The overall 5-year survival was:
      Stage IA: 100%, Stage IB: 72%, Stage IIA: 90%, and Stage IIB: 72%. The 5-year
      survival with no evidence of disease (NED) was: Stage IA: 100%, Stage IB: 67%,
      Stage IIA: 90%, and Stage IIB: 50%. Patients with bulky (> 5 cm) tumors had a
      shorter overall and NED survival than patients with nonbulky tumors (53% vs. 83%;
      p = 0.0008 and 44% vs. 78%; p = 0.0001, respectively). Thirty-nine tumor
      recurrences (39 out of 125 = 31%) occurred and were scored as local (23 out of
      125 = 18.3%), if initial failure had a local component, or distant (16 out of 125
      = 12.7%), if initial failure was distant only. Patients with bulky (more than 5
      cm) tumors (32 out of 125) were more likely to experience a recurrence (18 out of
      32 = 56%) than patients with nonbulky tumors (21 out of 93 = 22%; p = 0.0004).
      The initial site of recurrence was more likely to be local for bulky tumors (14
      out of 18 = 78%) than for nonbulky tumors (9 out of 21 = 43%; p = 0.03). The
      probability of a recurrence increased with the number of involved parametria
      (none: 20 out of 78 = 25%; one: 12 out of 34 = 35%; two: 7 out of 13 = 54%; p =
      0.04 for linear trend), as did the probability that the initial failure was
      distant rather than local (none: 4 out of 20 = 20%; one: 7 out of 12 = 58%; two:
      5 out of 7 = 71%; p = 0.01 for linear trend). Positive lymph nodes, vessel
      invasion, and low hemoglobin level all correlated with an increased risk of a
      recurrence (RR 2.41, p = 0.004; RR 2.20, p = 0.01; OR 2.02, p = 0.01,
      respectively). There were 46 complications among 37 (29%) patients. The incidence
      of grade 4 complications was 8.8% (11 out of 125). History of pelvic surgery and
      bulky tumor were significant predictors of a grade 4 complication (p < 0.0001 and
      0.021, respectively). Also, a dose rate to point A of > 0.6 Gy/h increased the
      chance of a grade 4 complication (p = 0.007). CONCLUSION: For patients with FIGO
      Stage I or II cervical carcinoma, tumor size was more predictive of local
      recurrence than was overall stage, and the extent of parametrial involvement was
      strongly predictive of distant recurrence, as was the stage. These findings
      suggest that tumor size and extent of parametrial involvement should be
      incorporated into the staging system. Patients with bulky tumors had a shorter
      survival and were more likely to experience a grade 4 toxicity of therapy. Dose
      rate to point A of > 0.6 Gy/h was associated with the increased risk of grade 4
      complications.

PMID- 7635772
TI  - Radiation therapy alone for adenocarcinoma of the uterine cervix.
AB  - PURPOSE: Radiation therapy alone for adenocarcinoma of the cervix is currently
      evaluated by the accumulation of long-term results because of the low incidence
      of this disease. MATERIALS AND METHODS: Fifty-eight patients with adenocarcinoma
      of the cervix treated with radiation therapy alone between 1961 and 1988 were
      studied. The radiation therapy consisted of a combination of intracavitary and
      external pelvis irradiation. Intracavitary treatment was performed with low dose
      rate and/or high dose rate sources. RESULTS: The 5-year survival rates for Stages
      I, II, III, and IV were 85.7%, 66.7%, 32.3%, and 9.1%, respectively, and the 10
      year survival rates were 85.7%, 60.0%, 27.6%, and 9.1%, respectively. The local
      control rate with high dose rate treatment was 45.5%, significantly lower than
      85.7% and 72.7% with low and mixed dose rate treatments, respectively. Five-year
      survival and local control rates by tumor volume were 68.6% and 80.0% for small
      tumors, 63.6% and 66.0% for medium tumors, and 14.4% and 18.2% for large tumors,
      respectively. The survival rate and local control rate for large tumors were
      significantly lower than those for small and medium tumors. Multiple regression
      analysis indicated that stage and tumor volume were independent variables for
      survival and local control, respectively. Isoeffective dose expressed by time
      dose fractionation (TDF) was not associated with local control. Radiation
      complications developed in 10 patients (17.2%), most of which were of moderate
      degree. CONCLUSION: Radiation therapy alone for adenocarcinoma of the cervix was
      regarded to be an effective treatment, comparable to combination therapy of
      surgery and radiation therapy.

PMID- 7635771
TI  - Proliferation measurements with flow cytometry Tpot in cancer of the uterine
      cervix: correlation between two laboratories and preliminary clinical results.
AB  - PURPOSE: To assess the prognostic value of the pretreatment potential doubling
      time (Tpot) in carcinoma of the uterine cervix, relative to other established
      clinical factors. METHODS AND MATERIALS: Fifty-two patients with cervical cancer
      were studied prospectively from March 1991 to October 1993. Pretreatment
      evaluation included examination under anesthesia and tumor biopsy 6 h following
      the intravenous administration of bromodeoxyuridine (200 mg). Tpot was determined
      by deriving the labeling index (LI) and S-phase synthesis time (Ts) using flow
      cytometry. Six patients were not evaluable and excluded. The remaining 46
      patients (average age 55 years) were treated uniformly with radical radiation
      therapy. There were 39 squamous carcinomas and 7 adenocarcinomas. Federation
      Internationale de Gynecologie et d'Obstetrique (FIGO) stages were: Ib and IIa, 12
      patients; IIb, 18 patients; III and IV, 16 patients. The median external beam
      dose was 50 Gy (range, 45-52.8 Gy) delivered in 25 fractions. The median
      intracavitary dose was 40 Gy (range. 25.5-40 Gy) delivered with a single line
      source to a point 2 cm lateral of the midline, with a mean dose rate of 0.71
      Gy/h. The median overall treatment time was 45 days (range, 34-73 days). As of
      July 31, 1994, 12 patients had died of disease, and the average follow-up for
      alive patients was 1.4 years (range, 0.5-3.3 years). RESULTS: There were 27
      tumors with diploid deoxyribonucleic acid (DNA) content and 19 tumors were
      aneuploid. The median and mean Tpot for the 46 patients were 5.5 and 6.6 days,
      respectively [range, 2.0-25.6 days; coefficient of variation (CV), 74%]. For 25
      patients where Tpot measurements were performed at two separate laboratories,
      there was a fair correlation (r = 0.74), but systematic differences were detected
      suggesting that the lack of agreement was not simply due to intratumoral
      variation. To date, 30 patients remained disease free, while 8 patients had
      pelvic failure and 9 patients developed distant metastases as the first failure
      site (1 patient developed both at the same time). In univariate analysis, the
      only significant prognostic factor for disease-free survival was tumor size (p =
      0.004). A short Tpot (or high LI) and long overall treatment time (OTT) were
      weakly associated with poorer disease-free survival, although not statistically
      significant (1/Tpot, p = 0.14; LI, p = 0.23; OTT, p = 0.04). Age, FIGO stage,
      hemoglobin level, S-phase fraction, DNA ploidy, and Ts were not associated with
      disease-free survival. Multiple regression analysis was not performed because of
      the relatively small number of patients and short follow-up. CONCLUSIONS: Tpot
      values determined with current techniques by different laboratories cannot be
      used interchangeably for the purpose of therapy decisions. Vigorous quality
      assurance and standardization of the laboratory procedures and analysis methods
      are important to reduce interlaboratory variation. In this uniformly treated
      group of patients with cancer of the uterine cervix, traditional clinical
      prognostic factors remain the most important. Preliminary data suggest that the
      flow cytometry-determined Tpot and labeling index predict for disease-free
      survival, although a larger number of patients with longer follow-up is required
      to assess the true prognostic significance of these assays and to determine if
      their effect is independent of other clinical factors.

PMID- 7635773
TI  - Effect of balloon occluded arterial infusion of anticancer drugs on the prognosis
      of cervical cancer treated with radiation therapy.
AB  - PURPOSE: The effect of local injection of anticancer drugs by balloon catheter,
      i.e., balloon occluded arterial infusion (BOAI), on the prognosis of cervical
      cancer treated with radiotherapy were retrospectively estimated. METHODS AND
      MATERIALS: Sixty-five patients with cervical cancer (Stage I-IV) treated by
      irradiation were included in the study. Among the 65 cases, 2 were in Stage I, 13
      in Stage II, 40 in Stage III, and 10 in Stage IV. Patients who received surgical
      resection were excluded. Thirty-nine patients received BOAI and 44 received
      brachytherapy. Twenty-six patients were not indicated for BOAI because of
      insufficient renal function, hepatic complications, hematological complications,
      and refusal from the patients. Cisplatin (0.9-1.7 mg/kg), Adriamycin (0.7-0.9
      mg/kg), and Pepleomycin (0.4-0.6 mg/kg) were administered simultaneously into the
      bilateral internal iliac arteries by BOAI. External irradiation was given by 10
      MV x-ray. Total dose administered to the regional lymph nodes by the external
      irradiation was 48.3 +/- 8.7 Gy. Radium was used at brachytherapy. The dose
      delivered by the brachytherapy at point A was 45.3 +/- 14.9 Gy. Patients without
      brachytherapy received 26.1 +/- 19.1 Gy of boost irradiation by the external
      photon beam. The survival probabilities of the patients were calculated by Kaplan
      Meier method. RESULTS: The 5-year survival rates of the Stage III patients with
      and without BOAI were 53 +/- 13% and 24 +/- 18%, respectively (p = 0.036). By
      multivariate analyses using Cox's proportional hazard model, stage and BOAI were
      selected as significant predictors of the prognosis. Transient bone marrow
      suppression was observed in about half of the patients with BOAI. No significant
      increase of the incidence of the late radiation damage by BOAI in rectum or in
      urinary bladder was observed. CONCLUSION: Balloon occluded arterial infusion of
      anticancer drugs may improve the prognosis of the patients with cervical cancer
      without increasing the incidence of the late radiation damage. A larger scale
      prospective randomized study is desired.

PMID- 7635774
TI  - Electron beam therapy is not inferior to superficial x-ray therapy in the
      treatment of skin carcinoma.
AB  - PURPOSE: To compare recurrence rates and cosmetic results after electron beam
      therapy vs. superficial x-ray therapy for nonmelanoma skin carcinoma. METHODS AND
      MATERIALS: A retrospective analysis was performed on 389 histologically confirmed
      basal cell and squamous cell carcinomas of the skin, treated with either
      superficial x-rays or electron beam therapy, with regard to local control rates
      and cosmetics, as scored with an arbitrary three-point scale. RESULTS: The
      overall local recurrence rate was 4.9% (19 out of 389). For small tumors
      (irradiated surfaces < or = 10 cm2) a local recurrence rate of 2.2% was observed,
      both after electron beam therapy and after superficial x-ray therapy. Tumor size
      and previous treatment proved to be important prognostic factors with regard to
      control rate. The well-fractionated electron beam therapy yielded better cosmetic
      results than the large fraction superficial x-ray therapy. CONCLUSION: Electron
      beam treatment is not inferior to superficial x-ray treatment and even better for
      larger tumors. The inferior results of electron beam therapy reported in
      literature might be due to technical factors, which are discussed.

PMID- 7635775
TI  - Vulvar carcinoma.
AB  - PURPOSE: Controversies exist regarding the use of radiation therapy in the
      treatment of vulvar carcinoma. A retrospective review was performed to evaluate
      our institution's experience with surgery and radiation for this disease. METHODS
      AND MATERIALS: The medical records of 47 patients treated for squamous cell
      carcinoma of the vulva at our institution (1974-1992) were reviewed for TNM stage
      (AJCC criteria), treatment modality, and associated 5-year local control and
      survival based on Kaplan-Meier analysis. RESULTS: Twenty-eight patients (60%)
      presented with Stage I and II disease and their 5-year survival was 69%. Stage
      III patients accounted for 12 (25%) of the patients and their 5-year survival was
      73%. Seven patients presented with Stage IV disease and five died within 13
      months of diagnosis after predominantly palliative therapy. The 40 patients with
      Stages I, II, and III disease were treated aggressively and were further
      evaluated for treatment-modality-associated survival and local control. Radiation
      therapy was used as primary treatment in nine patients, of whom seven were
      treated with radiation alone and two were treated postoperatively after wide
      excision. Surgery alone was performed in 31 patients consisting of either radical
      vulvectomy (20 patients) or wide excision (11 patients). When comparing outcomes
      of radical vulvectomy vs. radiation therapy, we noted that the 5-year actuarial
      survivals were comparable (74% for either modality), despite the presence of more
      favorable prognostic factors in the group treated with radical vulvectomy.
      Patients treated with wide excision alone had a trend for a poorer 5-year
      actuarial survival (51%) and local control (50%). CONCLUSIONS: Radical vulvectomy
      offers good locoregional control and survival. This retrospective review further
      supports the use of radiation therapy with conservative surgery as an alternative
      treatment option for patients with vulvar carcinoma treated with curative intent.
      In contrast, the use of wide excision alone should be performed with caution due
      to a higher locoregional failure rate. The role of appropriately prescribed
      radiation therapy should be further investigated in prospective clinical trials.

PMID- 7635776
TI  - Damage and morbidity from pneumonitis after irradiation of partial volumes of
      mouse lung.
AB  - PURPOSE: The aims of this study were to: (a) define the relationship of dose and
      volume irradiated to damage and morbidity in mouse lung, (b) determine the
      threshold volume for morbidity after partial lung irradiation; and (c) determine
      whether the response to radiation of mouse lung is independent of the region
      irradiated. METHODS AND MATERIALS: C3Hf/Kam female mice were used in this study.
      The fractional volume of the lung to be irradiated was determined by two methods,
      weights and computed tomography (CT) scanning. Two experiments were performed to
      define the volume effect and to determine whether the response of the mouse lung
      to radiation was homogeneous. In the first experiment, single doses of x-rays
      ranging from 12 to 20 Gy were given to partial volumes of 84%, 70%, and 40%
      including the base, 50%, 33%, and 17% including the apex, to 43% in the middle,
      and to the sum of 57% as 17% in the apex and 40% in the base. In the second
      experiment, the same volumes of 50% and 70-75% in the apex and base of the lung
      were irradiated with single doses ranging from 12-19.25 Gy. Morbidity from
      radiation pneumonitis was quantitated by two end points, breathing rate and
      lethality between 12 and 32 weeks after irradiation. Damage was assessed by
      histopathological evidence of pneumonitis. RESULTS: Clear well-defined dose
      response curves were obtained for both breathing rate and lethality after all
      volumes irradiated. There was a clear volume-dependent shift of the dose-response
      curves for breathing rate and lethality at 28 weeks after irradiation, the end of
      the pneumonitis phase of damage, to higher doses compared with these data after
      whole-lung irradiation. In addition, the slopes of the dose-response curves for
      irradiation of partial lung volumes were more shallow compared to those after
      whole-lung irradiation. Increases in breathing rate correlated with lethality
      when the volume irradiated was equal to or greater than 50% of the reference
      volume. However, after irradiation of volumes smaller than 40%, breathing rate
      increases were not accompanied by death. A heterogeneous response of the mouse
      lung to radiation was observed in the first experiment and confirmed by the
      second experiment. For a given volume irradiated, the isoeffect dose was always
      less for the base than for the apex of the lung. The threshold volume for
      breathing rate changes was less than 17 and 40% when the irradiated volumes
      involved the apex and base, respectively. For lethality, the threshold volume was
      between 40 and 70% for the base and greater than 50% for the apex of the lung.
      Finally, damage as assessed by histological evidence of pneumonitis was observed
      in the irradiated area only. CONCLUSIONS: (a) The volume effect was resolvable in
      mice, (b) the volume effect in mouse lung exhibits a clear threshold for
      morbidity, (c) the threshold volume for morbidity is dependent on the end point,
      (d) the response of mouse lung is heterogeneous, dependent on the site
      irradiated, and is always greater for the same volumes irradiated in the base
      than the apex, and, (e) histopathological damage does not always produce
      observable morbidity.

PMID- 7635777
TI  - Fibroblast radiosensitivity versus acute and late normal skin responses in
      patients treated for breast cancer.
AB  - PURPOSE/OBJECTIVE: To determine if the radiosensitivity of normal human skin
      fibroblasts, measured in early passage cultures, is significantly correlated with
      the degree of acute or late normal skin damage in patients treated for breast
      cancer with radiotherapy. METHODS AND MATERIALS: In the 1970s, a series of breast
      cancer patients was treated at the Department of Oncology in Gothenburg, Sweden
      with postoperative irradiation to the parasternal region. Patients were treated
      bilaterally using different fractionation schedules and doses to the right and
      left fields. Peak acute reactions were scored on a six-point scale, and skin
      erythema was measured by reflectance spectrophotometry. Telangiectasia was graded
      over time on a six-point scale. In April 1992, two small skin biopsies were
      obtained from 22 patients in two treatment groups (i.e., four dose-fractionation
      schedules) and, using either delayed or immediate plating, fibroblast
      radiosensitivity was measured in early passage cultures by clonogenic survival,
      after high and low dose-rate irradiations. Survival at 2.0 Gy (SF2) was
      calculated from complete survival curves. RESULTS: To test assay reproducibility,
      SF2 values derived from paired biopsies of the same patient (12 cases) were
      compared. A reasonably good correlation (p = 0.075) was obtained for SF2s
      determined by high dose-rate irradiations with immediate plating, but not for
      delayed plating or low dose-rate treatments. The median coefficient of variation
      in the replicate SF2s after high dose-rate treatment and immediate plating was
      13%, suggesting that the poor correlation in paired SF2 values is due to the
      magnitude of the uncertainty in SF2 relative to the overall spread in SF2 values
      between patients (CV = 28%). Individual SF2 values and averaged values from
      patients with data from two biopsies were compared with the acute and late
      clinical reactions. A significant negative correlation was found between SF2 and
      relative clinical response, but only when averaged high dose-rate SF2 values and
      telangiectasia scores were compared. There was no significant correlation between
      average SF2 values and acute responses or between individual SF2 measurements and
      either the acute or late clinical response. CONCLUSION: The results of this study
      suggest that the degree of late telangiectasia is at least partially dependent
      upon the intrinsic cellular radiosensitivity of normal fibroblasts, but the
      relationship is not clear cut. Multiple replicate assays are necessary to obtain
      reliable estimates of fibroblast SF2 values using current techniques.

PMID- 7635778
TI  - Effect of paclitaxel (taxol) alone and in combination with radiation on the
      gastrointestinal mucosa.
AB  - PURPOSE: Paclitaxel is a potentially useful drug for augmenting the cytotoxic
      action of radiotherapy because it has independent cytotoxic activity against
      certain cancers and blocks cells in the radiosensitive mitotic phase of the cell
      cycle. However, all rapidly proliferating tissues, both normal and neoplastic,
      may be affected by this therapeutic strategy. The aim of this study was to define
      the in vivo response of rapidly dividing cells of the small bowel mucosa to
      paclitaxel given alone and in combination with radiation. METHODS AND MATERIALS:
      Mice were given single IV doses of 10 or 40 mg/kg paclitaxel or four doses of 10
      mg/kg paclitaxel at 6, 12, or 24 h intervals. The kinetics of mitotic arrest and
      apoptosis in jejunal crypts of mice at 1-24 h after treatment were defined
      histologically. An in vivo stem cell microcolony assay was used to assess the
      radiosensitizing potential of paclitaxel when radiation was delivered at the peak
      of mitosis and at 24 h after drug treatment. RESULTS: Paclitaxel blocked jejunal
      crypt cells in mitosis and induced apoptosis in a dose-dependent manner.
      Fractionating the paclitaxel dose over 1-4 days did not result in any greater
      accumulation of mitotically blocked cells than did a single dose. Mitosis peaked
      2-4 h after paclitaxel and returned to near normal by 24 h. Apoptosis lagged
      several hours behind mitosis and peaked about 6 h later than mitosis. Despite
      these kinetic perturbations, there was little or no enhancement of radiation
      effect when single doses were delivered 2-4 h after paclitaxel administration.
      The maximum sensitizer enhancement ratio of 1.07 observed after a single
      paclitaxel dose of 40 mg/kg is consistent with independent crypt cell killing.
      Conversely, when radiation was given 24 h after paclitaxel, a significant
      protective effect of the drug (SER 0.89-0.92), most probably due to a
      regenerative overshoot induced by paclitaxel, was observed. CONCLUSION: Stem
      cells of the jejunal mucosa determining radiation response were not
      radiosensitized by paclitaxel with the drug concentrations and dose delivery
      schedules used, although additive cytotoxicity was observed with the highest drug
      dose. A radioprotective effect was observed when radiation was given 24 h after
      paclitaxel administration.

PMID- 7635779
TI  - Tumor oxygenation in a transplanted rat rhabdomyosarcoma during fractionated
      irradiation.
AB  - PURPOSE: To quantify the changes in tumor oxygenation in the course of a
      fractionated radiation treatment extending over 4 weeks. METHODS AND MATERIALS:
      Rhabdomyosarcomas R1H of the rat were irradiated with 60Co-gamma-rays with a
      total dose of 60 Gy, given in 20 fractions over 4 weeks. Oxygen partial pressure
      (pO2) in tumors was measured at weekly intervals using polarographic needle
      probes in combination with a microprocessor-controlled device (pO2
      Histograph/KIMOC). The pO2 measurements were carried out in anesthetized animals
      under mechanical ventilation and in respiratory and hemodynamic steady state.
      Tumor pO2 values were correlated to the arterial oxygen pressure paO2, arterial
      pCO2, and pH determined with a blood gas analyzer. RESULTS: Tumor oxygenation did
      not change significantly during the 3 weeks of irradiation (up to 45 Gy), from a
      median pO2 of 23 +/- 2 mmHg in untreated controls to 19 +/- 4 mmHg after the
      third week. The decrease of the number of pO2 values between 0 and 5 mmHg
      indicated that an improved oxygenation in the tumors occurred. However, with
      increasing radiation dose (fourth week, 60 Gy) a significant decrease in tumor
      oxygenation to a median pO2 of 8 +/- 2 mmHg and a rapid increase in the frequency
      of pO2 values (35 +/- 4%) between 0 and 5 mmHg was found. CONCLUSION: Improved
      oxygenation in rhabdomyosarcomas R1H was only present in the early phase of the
      fractionated irradiation. Radiation does above 45 Gy led to a considerable
      decrease of tumor oxygenation in the later phase of irradiation.

PMID- 7635780
TI  - Radiation sensitivity of Merkel cell carcinoma cell lines.
AB  - PURPOSE: Merkel cell carcinoma (MCC), being a small cell carcinoma, would be
      expected to be sensitive to radiation. Clinical analysis of patients at our
      center, especially those with macroscopic disease, would suggest the response is
      quite variable. We have recently established a number of MCC cell lines from
      patients prior to radiotherapy, and for the first time are in a position to
      determine their sensitivity under controlled conditions. METHODS AND MATERIALS:
      Some of the MCC lines grew as suspension cultures and could not be single cell
      cloned; therefore, it was not possible to use clonogenic survival for all cell
      lines. A tetrazolium based (MTT) assay was used for these lines, to estimate cell
      growth after gamma irradiation. Control experiments were conducted on
      lymphoblastoid cell lines (LCL) and the adherent MCC line, MCC13, to demonstrate
      that the two assays were comparable under the conditions used. RESULTS: We have
      examined cell lines from MCC, small cell lung cancer (SCLC), malignant melanomas,
      Epstein Barr virus (EBV) transformed lymphocytes (LCL), and skin fibroblasts for
      their sensitivity to gamma irradiation using both clonogenic cell survival and
      MTT assays. The results show that the tumor cell lines have a range of
      sensitivities, with melanoma being more resistant (surviving fraction at 2 Gy
      (SF2) 0.57 and 0.56) than the small cell carcinoma lines, MCC (SF2 range 0.21
      0.45, mean SF2 0.30, n = 8) and SCLC (SF2 0.31). Fibroblasts were the most
      sensitive (SF2 0.13-0.20, mean 0.16, n = 5). The MTT assay, when compared to
      clonogenic assay for the MCC13 adherent line and the LCL, gave comparable results
      under the conditions used. CONCLUSION: Both assays gave a range of SF2 values for
      the MCC cell lines, suggesting that these cancers would give a heterogeneous
      response in vivo. The results with the two derivative clones of MCC14 (SF2 for
      MCC14/1 0.38, MCC14/2 0.45) would further suggest that some of them may develop
      resistance during clonogenic evolution.

PMID- 7635781
TI  - Study of dosimetric penumbra due to multileaf collimation on a medical linear
      accelerator.
AB  - PURPOSE: Investigations of dosimetric penumbra produced by multileaf collimation
      on a medical linear accelerator are presented. METHODS AND MATERIALS: Multileaf
      collimators (MLCs) can be designed with at least three different shaped leaf-end
      profiles: straight, divergent, and curved. Assessment of the dosimetric effects
      of the collimator edge profiles was implemented using a fast Fourier transform
      (FFT) convolution algorithm. Accelerator source intensity was considered to have
      a Gaussian distribution. The calculated dose profile, for a source-to-surface
      distance of 100 cm and at depth of 10 cm in a water phantom, was fitted to a
      penumbral-forming function from which the penumbral width between 80% and 20% of
      the central axis dose was obtained. RESULTS: Calculation performed at various
      field sizes showed that curved collimator leaf-end produces a wider penumbra than
      the diverging collimator leaf-side. Film measurements agreed with the
      calculations within an uncertainty of less than 2 mm. The effect of backup jaws
      for the MLC and of the lower pair of diverging diaphragms on dosimetric penumbra
      was also investigated. CONCLUSIONS: This study is useful for characterizing
      collimator edge effects and for optimizing new collimator designs.

PMID- 7635782
TI  - Effect of increasing vascular hydraulic conductivity on delivery of
      macromolecular drugs to tumor cells.
AB  - PURPOSE: To examine the assumption that increasing the hydraulic conductivity Lp
      of microvessels (by such strategies as radiation, hyperthermia, or inducing
      inflammation) improves the transport of macromolecular drugs to tumors. METHODS
      AND MATERIALS: A theoretical model is used to investigate the effect of varying
      Lp on macromolecular transport in spherical tumor nodules. The model is
      generalized to nonspherical tumors. The equations governing fluid flow in the
      tumors are solved numerically to obtain the pressure in the interior, and
      macromolecule fluxes are deduced using Starling's equation. RESULTS: Because of
      the interaction of two opposing effects, the filtration rate at the tumor center
      is maximized at an "optimum" value of Lp, which depends strongly on tumor size.
      Only for tumor nodules smaller than about 0.2 cm across is this value lower than
      the actual estimated value. By considering spheroidal tumor nodules, it is found
      that dependence on shape is much weaker than dependence on size, except for
      extremely elongated or flattened shapes. CONCLUSIONS: While total fluid
      filtration for the entire tumor region always increases with increasing Lp, the
      local filtration rate at points inside the tumor decreases if the tumor is larger
      than about 0.2 cm, leading to a less uniform distribution of the drug, and
      therapeutic disadvantage. Increased vessel leakiness is an unlikely explanation
      for reported experimental findings that hyperthermia and inflammation result in
      more uniform distributions of monoclonal antibodies throughout tumors much larger
      than 0.2 cm.

PMID- 7635783
TI  - Twice-per-day fractionated high versus continuous low dose rate intracavitary
      therapy in the radical treatment of cervical cancer: a nonrandomized comparison
      of treatment results.
AB  - PURPOSE: To compare the efficacy of two twice-per-day fractionated high dose rate
      (HDR) brachytherapies with a historical control group treated with low dose rate
      (LDR) brachytherapy for cervical cancer patients. METHODS AND MATERIALS: From
      1985 to 1988, 92 patients with cancer of the cervic were treated by remote
      controlled, HDR brachytherapy, six fractions of 7 Gy per fraction (42 Gy) at
      point A (HDR-6). Fifty-seven patients were treated with four fractions of 8 Gy
      per fraction (32 Gy) at point A (HDR-4). A twice-per-day program was used for all
      HDR patients by two split courses. As a historical control, treatment results of
      259 patients treated with LDR brachytherapy (40 Gy in two split courses) were
      compared with those of the two HDR regimens. All patients received whole pelvic
      external irradiation, 36-45 Gy (mostly 40 Gy) before brachytherapy. RESULTS: Five
      year local control rates were not significantly different for the three groups
      (HDR-6 = 82.0%, HDR-4 = 85.5%, and LDR = 89.5%, respectively). Five-year survival
      rates were also comparable (67.7%, 77.9%, and 74.1%, respectively). However, late
      complications were lower in HDR-4 than HDR-6 (11.0% vs. 25.6%). CONCLUSIONS: Both
      5-year local control and survival rates were comparable among the three groups.
      However, HDR-4, which was more biologically equivalent to our LDR regimen, showed
      fewer complications compared to HDR-6. In addition, our twice-per-day schedule
      shortened the hospital stay.

PMID- 7635784
TI  - Patterns of failure following bone marrow transplantation for metastatic breast
      cancer: the role of consolidative local therapy.
AB  - PURPOSE: The purpose of this analysis is to evaluate the patterns of failure and
      the role of local therapy in conjunction with bone marrow transplantation (BMT)
      for metastatic or recurrent breast cancer. METHODS AND MATERIALS: Between June
      1986 and November 1991, 46 patients with hormone unresponsive metastatic or
      recurrent breast cancer underwent high dose chemotherapy (HDC) with hematopoietic
      stem cell support. The most commonly used preparative regimen consisted of
      thiotepa (750 mg/m2), cisplatin (150 mg/m2), and cyclophosphamide (120 mg/kg)
      followed by autologous BMT. Consolidative surgery or irradiation was considered
      in patients whose cancer responded to BMT and had localized sites of disease.
      RESULTS: Six patients (13%) died of BMT-related complications. Of the remaining
      40 patients, 22 were candidates for consolidative therapy, and 18 of those
      patients received consolidative irradiation (17 patients) or surgery (1 patient)
      to one or more sites. At median follow-up of 27 months (range, 20-78), 12 of 18
      (67%) patients have continuous local control at the 22 consolidated sites (1 of 4
      controlled at chest wall sites, 7 of 8 at regional nodal sites, 7 of 7 at
      localized bone sites, and 1 of 3 at lung/mediastinal sites). Toxicity of
      consolidative irradiation was mainly limited to myelosuppression in 6 of 17
      patients. Two patients did not complete the consolidative local therapy, one
      because of hematologic toxicity and one because of rapid systemic tumor
      progression during treatment. CONCLUSION: In patients with localized areas of
      extravisceral metastases, consolidative irradiation is feasible with acceptable
      hematologic toxicity. Consolidative irradiation can result in continuous local
      control, especially in isolated bone metastases and in regional nodal sites;
      however, the advantage is less clear in patients undergoing consolidative
      irradiation for chest wall failures. Because distant visceral metastases still
      remain a major site of failure after this HDC regimen, a more effective systemic
      therapy is needed. Consolidative local treatment should be considered in future
      HDC/BMT protocols for metastatic breast cancer, especially in localized nodal and
      osseous sites.

PMID- 7635785
TI  - Postoperative vaginal cuff irradiation using high dose rate remote afterloading:
      a phase II clinical protocol.
AB  - PURPOSE: In September 1989, a postoperative Phase II high dose rate (HDR)
      brachytherapy protocol was started for International Federation of Gynecology and
      Obstetrics (FIGO) Stage I endometrial adenocarcinoma. This review reports the
      overall survival, local control, and complication rates for the initial 63
      patients treated in this Phase II study. METHODS AND MATERIALS: High dose rate
      brachytherapy was delivered using an Iridium-192 HDR remote afterloader. Sixty
      three patients were entered into the Phase II protocol, each receiving two
      vaginal cuff treatments 1 week apart (range 4-12 days) with vaginal ovoids
      (diameter 2.0-3.0 cm). No patient received adjuvant external beam radiation. A
      dose of 32.4 Gy in two fractions was prescribed to the ovoid surface in 63
      patients. The first three patients treated at our institution received 15, 16.2,
      and 29 Gy, respectively, to determine acute effects. RESULTS: At a median follow
      up of 1.6 years (range 0.75-4.3 years) no patient has developed a vaginal cuff
      recurrence. One regional recurrence (1.6%) occurred at 1.2 years at the pelvic
      side wall. This patient is alive and without evidence of disease 7 months after
      completion of salvage irradiation, which resulted in the only vaginal stenosis
      (1.6%). Fourteen patients (22%) experienced vaginal apex fibrosis by physical
      exam, which was clinically symptomatic in four patients. Two patients reported
      stress incontinence; however, these symptoms were noted prior to their HDR
      therapy. One patient died 2.4 years after HDR therapy due to cardiovascular
      disease without evidence of cancer at autopsy. CONCLUSION: Preliminary results of
      our phase II HDR vaginal cuff protocol for postoperative FIGO Stage IA, Grade 3
      or Stage IB, Grade 1-2 patients demonstrate that 32.4 Gy in two fractions is well
      tolerated by the vaginal cuff mucosa. Local control appears comparable to our
      prior experience and others with low dose rate (LDR) brachytherapy. Additional
      patient accrual and further follow-up will better determine the late morbidity,
      local control, and overall survival of these patients.

PMID- 7635786
TI  - Multiple courses of high-dose total skin electron beam therapy in the management
      of mycosis fungoides.
AB  - PURPOSE: A retrospective analysis was undertaken to determine the indications
      for, the efficacy of, and the long-term complications of two courses of total
      skin electron beam therapy for mycosis fungoides. METHODS AND MATERIALS: A
      retrospective analysis of 15 patients with the pathologic diagnosis of mycosis
      fungoides treated in the Department of Radiation Oncology at Stanford University
      Medical Center between 1968 and 1990 was performed. All patients received two
      courses of high-dose electron beam therapy to the skin. The mean dose for the
      total skin treatment for the first course was 32.6 Gy and 23.4 Gy for the second
      course of treatment. RESULTS: Following the first course of total skin electron
      beam therapy, 11 of 15 had a complete response, with a mean duration of 11.6
      months. All patients received adjuvant therapies between the first and second
      courses of high-dose total skin electron beam therapy. The mean interval between
      the first and the second courses of therapy was 41.3 months. Patients were
      restaged prior to commencement of their second course of high-dose total skin
      electron beam therapy, resulting in upstaging in six. The second course of
      therapy resulted in six complete responses and nine partial responses. Twelve of
      these patients have since died, 1 is lost to follow-up, and 2 are living with
      disease. The long-term side effects in the two living patients include
      pigmentation changes, alopecia, and diffuse xerosis. CONCLUSION: Delivery of two
      courses of total skin electron beam therapy is technically feasible, tolerable,
      and efficacious. The dose to the total skin was reduced for the second course of
      therapy in all cases. The criteria used to screen patients included initial good
      response to total skin electron treatment, long disease-free interval, exhaustion
      of other therapeutic modalities, and generalized skin involvement at relapse.
      Long-term toxicities were mild in severity and generally consisted of generalized
      xerosis, scattered telangiectasias, pigmentation changes, and partial alopecia.

PMID- 7635787
TI  - Early tolerance of different organs to fast fractionation in clinical practice.
AB  - PURPOSE: To assess the feasibility of accelerated hyperfractionated radiotherapy
      in the treatment of breast, abdominal cavity, and pelvic tumors. METHODS AND
      MATERIALS: Between August 1989 and March 1993, 39 patients were treated in
      Portsmouth by an accelerated, hyperfractionated regimen giving 45 to 54 Gy three
      times a day over 12 days. Twenty patients had abdominal cavity or pelvic tumors
      and 19 patients breast carcinoma, 9 of whom were treated prophylactically after
      local excision. RESULTS: No local recurrence has been observed in the 19 patients
      with breast carcinoma, and out of the 20 with abdominal or pelvic tumors, 6
      showed complete regression and so far no severe late damage has been observed. In
      those patients who had pelvic or abdominal tumors treated, the acute toxicity
      varied widely from minimal to very intensive. No surgical intervention was
      necessary and most reactions settled within a 6-week period. CONCLUSION:
      Accelerated fractionation by small increments is well tolerated by the breast,
      pelvic, and abdominal organs.

PMID- 7635788
TI  - Effectiveness of brachytherapy in treating carcinoma of the vulva.
AB  - PURPOSE: Radical radiotherapeutic management of vulvar cancer often incorporates
      brachytherapy as a portion of the treatment regimen. However, few studies using
      this modality alone to manage vulvar cancer have been published. METHODS AND
      MATERIALS: Thirty four patients were treated with iridium-192 (192Ir)
      brachytherapy for vulvar cancer between 1975 and 1993 at Centre Alexis Vautrin.
      Twenty-one patients were treated at first presentation when surgery was
      contraindicated or declined. Of these patients, 12 had International Federation
      of Gynecology and Obstetrics Classification Stage III or IV disease, 8 were Stage
      II, 1 was Stage I, and 1 was Stage 0. Thirteen patients were treated for
      recurrent disease. Paris system rules for implantation and dose prescription were
      followed. The median reference dose was 60 Gy (range 53 to 88 Gy). At the time of
      analysis, 10 of 34 patients were alive. Median follow-up in these 10 patients was
      31 months (range: 21 months to 107 months). Fourteen of the 24 deaths were from
      causes other than vulvar cancer. RESULTS: Kaplan-Meier actuarial 5-year local
      control was 47% (95% confidence interval (CI) = 23 to 73%) and 5-year actuarial
      loco-regional control was 45% (95% CI = 21 to 70%). Kaplan-Meier actuarial 5-year
      disease-specific survival was 56% (95% CI = 33 to 76%) and actuarial 5-year
      survival was 29% (95% CI = 15 to 49%). Median time to death was 14 months. Subset
      analysis revealed a higher actuarial 5-year local control in patients treated at
      first presentation than those treated for recurrence (80 vs. 19%, log rank, p =
      0.04). Similarly, actuarial 5-year loco-regional control was higher in patients
      treated at first presentation (80 vs. 16%, log rank, p = 0.01). The two groups
      did not differ significantly in disease-specific or overall survival. The
      actuarial 5-year disease specific survival of 56% is somewhat less than the
      expected 5-year disease-specific survival after surgery in a group having a
      similar proportion of early stage, advanced stage, and recurrent vulvar cancer.
      CONCLUSIONS: Brachytherapy is an effective treatment for patients with carcinoma
      of the vulva who decline surgery or in whom surgery is contraindicated.

PMID- 7635789
TI  - Radiation-induced premature menopause: a misconception.
AB  - PURPOSE: To disprove the common view that women who have undergone irradiation to
      fields excluding the pelvis are at risk for radiation-induced premature
      menopause, we reviewed menstrual function and fertility among women treated with
      subtotal lymphoid irradiation for Hodgkin's Disease. METHODS AND MATERIALS:
      Treatment and follow-up records of all women less than age 50 at the time of
      diagnosis of Stage I or II supradiaphragmatic Hodgkin's Disease, treated with
      subtotal lymphoid irradiation alone and enrolled in radiotherapy trials from 1967
      to 1985, were reviewed. In addition, patients were surveyed regarding their
      menstrual status and fertility history. RESULTS: Thirty-six women, aged 10 to 40
      years, with normal menstrual function at the time of Hodgkin's diagnosis, were
      identified. Mean follow-up was 14 years, with a range of 1.25-22.75 years. The
      average radiation dose to mantle and paraaortic fields was 40-44 Gy; the
      calculated scatter radiation dose to the pelvis at the ovaries was 3.2 Gy. There
      were 38 pregnancies in 18 women; all offspring are normal. One of 36 women (2.7%)
      experienced premature menopause. The reported rate of premature menopause in
      women who have not undergone irradiation is 1-3%; not significantly different
      than the rate in our study. There is a syndrome whereby antibodies to several
      endocrine organs occur (including the ovary), which is associated with premature
      ovarian failure. This syndrome may be associated with prior radiation to the
      thyroid, such as that given by mantle irradiation for Hodgkin's Disease. We
      report such a case. CONCLUSION: There is little risk of premature menopause in
      women treated with radiation fields that exclude the pelvis. Women with presumed
      radiation-induced premature menopause warrant an evaluation to exclude other
      causes of ovarian failure, such as autoimmune disorders.

PMID- 7635790
TI  - Quality assurance for gamma knife stereotactic radiosurgery.
AB  - PURPOSE: This quality assurance program is designed for stereotactic
      radiosurgical units, gamma knife, to check and maintain the unit to preclude
      accidents and comply with current regulations. MATERIALS AND METHODS: Over 58
      stereotactic radiosurgical units using 201 focused 60Co beams have been installed
      in the last 7 years and are in use at hospitals throughout the world, with at
      least 11 additional units being prepared to come on-line in the next year. This
      system has been in use at the University of Pittsburgh Medical Center (UPMC) for
      7 years. A comprehensive quality assurance program has been developed. It
      includes the physics and dosimetry parameters and safety checks required by
      regulatory agencies. The program, based on over 7 years of experience in
      measurements, and used during the treatment of over 1500 patients, is separated
      into three aspects, namely physics, dosimetry, and safety. The UPMC program
      hopefully will indicate out-of-tolerance problems. Some quality assurance items
      are checked on a daily basis prior to patient treatment, while other aspects are
      checked on a weekly, monthly, and/or annual basis. A complete list of items with
      their respective time tables and tolerances is provided. RESULTS: Although
      experience shows very small margins of error, larger values were chosen to
      account for variations in equipment and techniques. CONCLUSIONS: Items included
      in this quality assurance program should indicate and/or preclude problems
      encountered in the use of this unit.

PMID- 7635791
TI  - The lack of impact of pelvic irradiation on small bowel mobility: implications
      for radiotherapy treatment planning.
AB  - PURPOSE: Small bowel contrast is frequently used during simulation for patients
      undergoing pelvic radiotherapy to assist in the design of blocks that exclude
      small bowel from the radiation field. In many instances, a large field is treated
      to 45 gray (Gy), followed by a field reduction to exclude the small bowel. This
      prospective study was designed to assess whether the position and mobility of the
      small bowel changed after the initial 45 Gy, thereby determining whether a
      special small bowel series done at initial simulation is applicable at the time
      of field reduction. METHODS AND MATERIALS: Twelve patients undergoing pelvic
      irradiation were given small bowel contrast for their initial simulation.
      Radiographs were taken with the bladder empty and the bladder full. The location
      of the small bowel and its displacement with bladder distention was measured.
      This entire procedure was repeated prior to field reduction (after 39.6-46.0 Gy).
      RESULTS: There was no demonstrable alteration in small bowel mobility after 39.6
      46.0 Gy. The approximate position of the small bowel relative to bony landmarks
      was unchanged. CONCLUSION: The position and mobility of the small bowel appears
      not to be affected by 39.6-46.0 Gy of pelvic radiotherapy. Therefore, it is
      reasonable to design reduced pelvic fields to exclude the small bowel based on
      special small bowel series done at initial treatment simulation.

PMID- 7635792
TI  - Effect of ocular implants of different materials on the dosimetry of external
      beam radiation therapy.
AB  - PURPOSE: To study the attenuation and scattering effects of ocular implants, made
      from different materials, on the dose distributions of a 6 MV photon beam, and 6,
      9, and 12 MeV electron beams used in orbital radiotherapy. METHODS AND MATERIALS:
      Central axis depth-dose measurements were performed in a polystyrene phantom with
      embedded spherical ocular implants using film dosimetry of a 6 MV photon beam and
      electron beams of 6, 9, and 12 MeV energy. The isodose distributions were also
      calculated by a computerized treatment planning system using computerized
      tomography (CT) scans of a polystyrene phantom that had silicone, acrylic, and
      hydroxyapatite ocular implants placed into it. RESULTS: Electron beam dose
      distributions display distortions both on the measured and calculated data. This
      effect is most accentuated for the hydroxyapatite implants, for which the
      transmissions through ocular implants are on the order of 93% for the 6 MV photon
      beam, and range from 60% for 6 MeV electrons to 90% for 12 MeV electrons.
      CONCLUSION: We studied the effect of ocular implants of various materials,
      embedded in a polystyrene phantom, on the dose distributions of a 6 MV photon
      beam, and 6, 9, and 12 MeV electron beams. Our investigations show that while 6
      MV photons experience only a few percent attenuation, lower energy electron beam
      with 60% transmission is not a suitable choice of treating tumors behind the
      ocular implants.

PMID- 7635793
TI  - Carcinoma of the cervix: patterns of care studies: review of 1978, 1983, and 1988
      1989 surveys.
AB  - PURPOSE: A review of the Patterns of Care Studies Process Survey data on
      carcinoma of the cervix conducted on patients in 1978, 1983, and 1988-89 was
      carried out to identify changes or trends in the demographics, evaluation, and
      treatment that might have occurred over this time period. METHODS AND MATERIALS:
      Patterns of Care Studies conducted surveys on patients treated by radiation
      therapy for cervical carcinoma in 1978, 1983, and 1988-89. These surveys have
      compiled demographic and treatment data on a total of 993 patients. There is
      outcome data for the 1978 and 1983 surveys, but not for the 1988-89 survey
      because follow-up has not been collected yet. The demographic and treatment
      delivery data on all three surveys has been reviewed and analyzed and is the
      subject of this study. RESULTS: There was no difference in the age distribution
      at the time of diagnosis of the patients in these surveys. The percentage of
      black patients remained constant in the three surveys, 19%, 17%, and 21%,
      respectively. The percentage of white patients was 76%, 78%, and 67%, but that of
      nonwhite/nonblack patients was 3%, 4%, and 12% (p < 0.001). The distribution of
      patients by stage was similar in the first two surveys. In the third survey,
      there was a decrease in the percentage of patients with Stage IA and IB (first =
      35%; second = 38%; third = 29%) with a concurrent increase in Stage IIIA and IIIB
      patients (first = 20%; second = 18%; third = 26%). The surveys showed a major
      change in the pretreatment evaluation tests used. There was a progressive
      decrease in the use of intravenous pyelogram (IVP) (86 to 42%), barium enema (58
      to 32%), cystoscopy for patients Stage IIB and higher (64 to 52%), and
      lymphangiography (18 to 14%). The use of abdominal or pelvic computed tomography
      dramatically increased from 6 to 70% between the first and third surveys. The use
      of 60Co units decreased from 35 to 2% from the first to the third survey [6 to 0%
      for short source-surface distance (SSD) 60Co units]. Point dose calculations for
      the intracavitary therapy increased from 78% in the 1978 survey to 95% in the
      third survey. As determined by the total dose delivered to the paracentral
      points, more patients (75.1%) were treated according to the Patterns of Care
      recommended guidelines in the 1988-89 survey than in the 1983 survey (63.6%).
      Chemotherapy was given to 12% of the patients undergoing radiation therapy during
      the period of the third survey, but these data are not available for the first
      and second surveys. CONCLUSION: Review of the Carcinoma of the Cervix Patterns of
      Care studies discloses significant changes in the demographics, patient
      evaluation, and radiation therapy techniques during the period of the studies.
      The potential impact of these changes on treatment outcome cannot be determined
      at this time until longterm follow-up for the 1988-89 survey is available, but
      improvements in the processes of care should lead to improvements in outcome.

PMID- 7635794
TI  - ASTRO Research Fellowship: apoptosis as a predictor of tumor response to
      radiation in stage IB cervical carcinoma. American Society for Therapeutic
      Radiology and Oncology.
AB  - PURPOSE: Levels of apoptosis predict for tumor responsiveness to radiation in
      various animal systems. To investigate the potential role of apoptosis as a
      predictor of response in human tumors, a retrospective review was undertaken of
      patients with adenocarcinoma of the cervix whose primary lesion at presentation
      measured at least 4 cm and who underwent definitive radiation therapy. A previous
      report had indicated that roughly half this group of patients should have a long
      term relapse free survival. METHODS AND MATERIALS: Pretreatment biopsy specimens
      of 44 patients with Stage IB adenocarcinoma of the cervix, whose primary lesion
      at presentation measured at least 4 cm in greatest dimension, were scored for
      apoptosis by two independent investigators without knowledge of the treatment
      outcome, and the results were averaged. Actuarial methods were used to assess
      overall survival, disease-free survival, determinate survival, and local control
      as a function of the baseline level of apoptosis. Patients ranged in age from 21
      to 87 years and were treated with definitive radiotherapy between 1964 and 1989.
      Follow-up for the surviving patients ranged from 1 to 278 months, with a mean of
      101 months. RESULTS: Patients whose tumors had a baseline level of apoptosis
      above the median value (2%) had a better overall survival than those with lower
      levels of apoptosis (p = 0.056). A similar trend for disease-free survival (p =
      0.32) and determinate survival (p = 0.27) did not reach statistical significance,
      perhaps because of the small number of patients. Because only 6 of the 44
      patients (13%) had a local tumor failure, it was not possible to establish a
      correlation between the pretreatment level of apoptosis and the local tumor
      control by radiation. CONCLUSION: The baseline level of apoptosis predicted for
      survival in patients with Stage IB cervical adenocarcinoma. Further investigation
      of the measurement of apoptosis as a potential predictive assay is warranted in
      other human tumor systems.

PMID- 7635795
TI  - Decision logic for retreatment of asymptomatic lung cancer recurrence based on
      positron emission tomography findings.
AB  - PURPOSE: The purpose of the study was to determine if Positron emission
      tomography (PET) 2-[F-18] fluoro-2-deoxy-D-glucose (FDG) imaging could detect
      subclinical local lung cancer recurrence and whether retreatment of such
      recurrence was feasible and beneficial. METHODS AND MATERIALS: Twenty patients
      with biopsy proven lung cancer were studied with Positron emission tomography for
      the purpose of detecting subclinical lung cancer recurrence over a period of 4.25
      years. All patients were treated with external radiation as part or all of their
      therapy. Twenty patients had baseline PET and computed tomography (CT) studies
      for comparison with later studies. Surviving patients had a total of 40
      sequential PET scans and 35 CT scans. The follow-up interval ranged from 5 to 40
      months posttreatment. The differential uptake ratio (DUR) was determined for
      regions of interest of increased FDG uptake. RESULTS: The median DUR value of the
      20 baseline PET studies was 5.59. The DUR value of greater than 3 was empirically
      selected as being positive for tumor detection. On baseline studies, PET had a
      100% correlation with the CT findings in regard to detection of the site of
      primary tumor involvement. Four of 20 patients showed areas of discordance in the
      mediastinal and hilar areas on initial PET and CT studies. Seven of 17 patients
      showed discordant posttreatment PET-CT findings. Two false positive PET studies
      were due to radiation pneumonitis and one to macrophage glycolysis in tumor
      necrosis. For detection of asymptomatic tumor recurrence, analysis of sequential
      PET and CT studies, biopsy results, and the patient's clinical course suggested
      that PET had a sensitivity of 100%, specificity of 89.3%, and accuracy of 92.5%.
      Computerized Tomography was found to have a sensitivity of 67%, specificity of
      85%, and accuracy of 82% for detection of such early-stage recurrence. Five
      patients went on to have retreatment with external irradiation based upon the PET
      evidence. Four retreated patients had biopsies that corroborated the positive PET
      findings, and one patient was retreated on the basis of the qualitative
      appearance of the posttreatment PET study. Two of the five retreated patients
      remain alive without evidence of tumor to 34 months following initial therapy.
      CONCLUSION: Positron emission tomography scanning appears to be effective in
      detecting and following the progression of recurrent lung cancer. Retreatment of
      patients with asymptomatic recurrent tumor has resulted in absent or decreased
      FDG activity. Monitoring of patients with PET may provide prolonged survival in
      patients who otherwise would fail treatment because of local tumor recurrence.

PMID- 7635796
TI  - The evolution of Radiation Therapy Oncology Group (RTOG) protocols for nonsmall
      cell lung cancer.
AB  - Over the past 2 decades, the Radiation Therapy Oncology Group (RTOG) has played a
      significant role in clarifying the role of radiation therapy (RT) in the
      treatment of nonsmall cell lung cancer (NSCLC). RTOG lung cancer research has
      evolved over this time period through a systematic succession of investigations.
      For unresectable NSCLC, the dependence of local tumor control and survival on
      total dose of standard fractionation RT, as well as pretreatment performance
      characteristics, was demonstrated in initial RTOG trials. Subsequently, further
      radiation dose intensification was tested using altered fractionation RT to total
      doses up to 32% higher than standard RT to 60 Gy, given as either
      hyperfractionation or accelerated fractionation, while attempting to retain
      acceptable normal tissue toxicity. These higher doses required rethinking of
      established RT techniques and limitations, as well as careful surveillance of
      acute and late toxicity. A survival advantage was shown for hyperfractionation to
      69.6 Gy, in favorable performance patients, compared to 60 Gy. Further testing of
      high dose standard RT will use three-dimensional, conformal techniques to
      minimize toxicity. RTOG further extended the theme of treatment intensification
      for unresectable NSCLC by evaluating combined chemotherapy (CT) and RT. Improved
      local control and survival was shown for induction CT followed by standard RT to
      60 Gy, compared to standard RT (60 Gy) and altered fractionation RT (69.6 Gy).
      The intent of current studies is to optimize dose and scheduling of combined CT
      and standard RT, as well as combined CT and altered fractionation RT.
      Noncytotoxic RT adjuvants, such as hypoxic cell sensitizers, nonspecific immune
      stimulants, and biologic response modifiers have also been studied. Resectable
      NSCLC has also been an RTOG focus, with studies of preoperative and postoperative
      RT, CT, and CT/RT, including the prognostic value of serum and tissue factors.
      RTOG studies have yielded incremental improvements in treatment outcome for
      NSCLC, better understanding of the disease dynamics, and a strong foundation for
      future investigations.

PMID- 7635798
TI  - Why actuarial estimates should be used in reporting late normal-tissue effects of
      cancer treatment ... now!

PMID- 7635797
TI  - Has the influence of treatment duration on local control of carcinoma of the
      cervix been defined?

PMID- 7635799
TI  - Changing patterns of care in carcinoma of the uterine cervix: need for cost
      benefit studies.

PMID- 7635800
TI  - The clinical status of Tpot as a predictor? Or why no tempest in the Tpot!

PMID- 7635801
TI  - Radiation therapy for adenocarcinoma of the uterine cervix: does the histology
      matter?

PMID- 7635802
TI  - Sarcoma of soft tissues: radiation sensitivity, treatment field margins,
      pathological margins, and dose--on Fein et al., IJROBP 32:969-976; 1995.

PMID- 7635803
TI  - In response to Bentzen et al., IJROBP 32:1531-1534; 1995.

PMID- 7635804
TI  - Clinical realization of 3D conformal intensity modulated radiotherapy: regarding
      Bortfeld et al., IJROBP 30:899-908; 1994.

PMID- 7635805
TI  - Proceedings of the American Society for Therapeutic Radiology and Oncology 37th
      annual meeting. Miami Beach, Florida, October 8-11, 1995. Abstracts.

PMID- 7635806
TI  - Streptococcal plasmid pIP501 has a functional oriT site.
AB  - DNA sequence analysis suggested the presence of a plasmid transfer origin-like
      site (oriT) in the gram-positive conjugative plasmid pIP501. To test the
      hypothesis that the putative oriT site in pIP501 played a role in conjugal
      transfer, we conducted plasmid mobilization studies in Enterococcus faecalis. Two
      fragments, 49 and 309 bp, which encompassed the oriT region of pIP501, were
      cloned into pDL277, a nonconjugative plasmid of gram-positive origin. These
      recombinant plasmids were mobilized by pVA1702, a derivative of pIP501, at a
      frequency of 10(-4) to 10(-5) transconjugants per donor cell, while pDL277 was
      mobilized at a frequency of 10(-8) transconjugants per donor cell. These results
      indicated that the oriT-like site was needed for conjugal mobilization. To
      demonstrate precise nicking at the oriT site, alkaline gel and DNA-sequencing
      analyses were performed. Alkaline gel electrophoresis results indicated a single
      stranded DNA break in the predicted oriT site. The oriT site was found upstream
      of six open reading frames (orf1 to orf6), each of which plays a role in conjugal
      transfer. Taken together, our conjugal mobilization data and the in vivo oriT
      nicking seen in Escherichia coli argue compellingly for the role of specific,
      single-stranded cleavage in plasmid mobilization. Thus, plasmid mobilization
      promoted by pVA1702 (pIP501) works in a fashion similar to that known to occur
      widely in gram-negative bacteria.

PMID- 7635807
TI  - Identification of cutC and cutF (nlpE) genes involved in copper tolerance in
      Escherichia coli.
AB  - It has been suggested previously that copper transport in Escherichia coli is
      mediated by the products of at least six genes, cutA, cutB, cutC, cutD, cutE, and
      cutF. A mutation in one or more of these genes results in an increased copper
      sensitivity (D. Rouch, J. Camakaris, and B. T. O. Lee, p. 469-477, in D. H. Hamer
      and D. R. Winge, ed., Metal Ion Homeostasis: Molecular Biology and Chemistry,
      1989). Copper-sensitive cutC and cutF mutants were transformed with a genomic
      library of E. coli, and copper-tolerant transformants were selected. Two distinct
      clones were identified, each of which partially restores copper tolerance in both
      the cutC and cutF mutants of E. coli. Subcloning, physical mapping, and sequence
      analysis have revealed that the cutC gene is located at 42.15 min on the E. coli
      genome and encodes a cytoplasmic protein of 146 amino acids and that the cutF
      gene is located at 4.77 min on the E. coli genome and is allelic to the nlpE gene
      independently identified by Silhavy and coworkers (W. B. Snyder, L. J. B. Davis,
      P. N. Danese, C. L. Cosma, and T. J. Silhavy, J. Bacteriol. 177:4216-4223, 1995).
      Results from the genetic mapping of the copper-sensitive mutations in the cutF
      mutant and sequencing of the cutC and cutF (nlpE) alleles from both cutC and cutF
      mutants indicate that both the cutC and cutF mutants are in fact double mutants
      altered in these two genes, and mutations in both the genes appear to be required
      for the copper-sensitive phenotype in each mutant.

PMID- 7635808
TI  - Overproduction of NlpE, a new outer membrane lipoprotein, suppresses the toxicity
      of periplasmic LacZ by activation of the Cpx signal transduction pathway.
AB  - The LamB-LacZ-PhoA tripartite fusion protein is secreted to the periplasm, where
      it exerts a toxicity of unknown origin during high-level synthesis in the
      presence of the inducer maltose, a phenotype referred to as maltose sensitivity.
      We selected multicopy suppressors of this toxicity that allow growth of the
      tripartite fusion strains in the presence of maltose. Mapping and subclone
      analysis of the suppressor locus identified a previously uncharacterized
      chromosomal region at 4.7 min that is responsible for suppression. DNA sequence
      analysis revealed a new gene with the potential to code for a protein of 236
      amino acids with a predicted molecular mass of 25,829 Da. The gene product
      contains an amino-terminal signal sequence to direct the protein for secretion
      and a consensus lipoprotein modification sequence. As predicted from the
      sequence, the suppressor protein is labeled with [3H]palmitate and is localized
      to the outer membrane. Accordingly, the gene has been named nlpE (for new
      lipoprotein E). Increased expression of NlpE suppresses the maltose sensitivity
      of tripartite fusion strains and also the extracytoplasmic toxicities conferred
      by a mutant outer membrane protein, LamBA23D. Suppression occurs by activation of
      the Cpx two-component signal transduction pathway. This pathway controls the
      expression of the periplasmic protease DegP and other factors that can combat
      certain types of extracytoplasmic stress.

PMID- 7635809
TI  - Direct correlation between overproduction of guanosine 3',5'-bispyrophosphate
      (ppGpp) and penicillin tolerance in Escherichia coli.
AB  - The penicillin tolerance exhibited by amino acid-deprived Escherichia coli has
      been previously proposed to be a consequence of the stringent response. Evidence
      indicating that penicillin tolerance is directly attributable to guanosine 3',5'
      bispyrophosphate (ppGpp) overproduction and not to some other effect of amino
      acid deprivation is now presented. Accumulation of ppGpp in the absence of amino
      acid deprivation was achieved by the controlled overexpression of the cloned relA
      gene, which encodes ppGpp synthetase I. The overproduction of ppGpp resulted in
      the inhibition of both peptidoglycan and phospholipid synthesis and in penicillin
      tolerance. The minimum concentration of ppGpp required to establish these
      phenomena was determined to be 870 pmol per mg (dry weight) of cells. This
      represented about 70% of the maximum level of ppGpp accumulated during the
      stringent response. Penicillin tolerance and the inhibition of peptidoglycan
      synthesis were both suppressed when ppGpp accumulation was prevented by treatment
      with chloramphenicol, an inhibitor of ppGpp synthetase I activation. Glycerol-3
      phosphate acyltransferase, the product of plsB, was recently identified as the
      main site of ppGpp inhibition in phospholipid synthesis (R. J. Health, S.
      Jackowski, and C. O. Rock, J. Biol. Chem. 269:26584-26590, 1994). The
      overexpression of the cloned plsB gene reversed the penicillin tolerance
      conferred by ppGpp accumulation. This result supports previous observations
      indicating that the membrane-associated events in peptidoglycan metabolism were
      dependent on ongoing phospholipid synthesis. Interestingly, treatment with beta
      lactam antibiotics by itself induced ppGpp accumulation, but the maximum levels
      attained were insufficient to confer penicillin tolerance.

PMID- 7635810
TI  - VirG, a Yersinia enterocolitica lipoprotein involved in Ca2+ dependency, is
      related to exsB of Pseudomonas aeruginosa.
AB  - Pathogenic yersiniae require Ca2+ for growth at 37 degrees C. They harbor closely
      related plasmids of about 70 kb that are essential for virulence. At 37 degrees C
      and in the absence of Ca2+ ions, these plasmids cause a decrease in growth rate
      and the release of large amounts of proteins called Yops. Here we describe the
      virG gene of Yersinia enterocolitica; virG is located just upstream of the virF
      gene, which encodes the transcriptional activator of some plasmid virulence
      factors. Analysis of the VirG amino acid sequence suggested that virG encodes a
      lipoprotein, which was confirmed by [3H]palmitate labeling of VirG-PhoA fusion
      proteins. A nonpolar virG mutant was constructed and found to be Ca2+ independent
      for growth at 37 degrees C but to still secrete Yops. This phenotype was
      complemented by the introduction of a plasmid harboring an intact virG gene. VirG
      was found to be homologous to ExsB, a protein encoded by a Pseudomonas aeruginosa
      gene located in the locus controlling exoenzyme S synthesis. Interestingly, the
      exsA gene, located just downstream of exsB, is also homologous to virF.

PMID- 7635811
TI  - Analysis of a Coxiella burnetti gene product that activates capsule synthesis in
      Escherichia coli: requirement for the heat shock chaperone DnaK and the two
      component regulator RcsC.
AB  - A 1.2-kb EcoRI genomic DNA fragment of Coxiella burnetti, when cloned onto a
      multicopy plasmid, was found to induce capsule synthesis (mucoidy) in Escherichia
      coli. Nucleotide sequence analysis revealed the presence of an open reading frame
      that could encode a protein of 270 amino acids. Insertion of a tet cassette into
      a unique NruI restriction site resulted in the loss of induction of mucoidy.
      Because of its ability to induce mucoidy, we designated this gene mucZ. Computer
      search for homologies to mucZ revealed 42% identity to an open reading frame
      located at 1 min of the E. coli chromosome. Interestingly, the C-terminal amino
      acid residues of MucZ share significant homology with the J domain of the DnaJ
      protein and its homologs, suggesting potential interactions between MucZ and
      components of the DnaK-chaperone machinery. Results presented in this paper
      suggest that E. coli requires DnaK-chaperone machinery for Lon-RcsA-mediated
      induction of capsule synthesis, as noticed first by S. Gottesman (personal
      communication). The induction caused by MucZ is independent of Lon-RcsA and is
      mediated through the two-component regulators RcsC and RcsB. DnaK and GrpE but
      not DnaJ are also required for the RcsB-mediated MucZ induction, and we propose
      that MucZ is a DnaJ-like chaperone protein that might be required for the
      formation of an active RcsA-RcsB complex and for the RcsC-dependent
      phosphorylation of RcsB. Discussions are presented that suggest three different
      roles for alternative forms of the DnaK-chaperone machinery in capsule
      production.

PMID- 7635813
TI  - Germination of myxospores from the fruiting bodies of Myxococcus xanthus.
AB  - Germination of myxospores from fruiting bodies of Myxococcus xanthus was examined
      under a light microscope as well as by analyzing the incorporation of [3H]uracil
      into the RNA fraction. Efficient germination was observed in 0.2% Casitone
      containing 8 mM MgSO4 and 1 mM CaCl2 at 30 degrees C. Under this condition,
      spherical myxospores were converted into rod-shaped vegetative cells within 5 to
      6 h. The germination was severely inhibited in the presence of 1 mM
      phenylmethylsulfonyl fluoride, a protease inhibitor, indicating that a serine
      protease(s) is required for the myxospore germination. EGTA (1 mM) also
      completely blocked germination, indicating that Ca2+ plays an important role in
      myxospore germination. In 1% Casitone without added Mg2+ and Ca2+ or 0.2%
      Casamino Acids with 8 mM MgSO4 and 1 mM CaCl2, myxospores lost their refractility
      under a phase microscope, while no RNA synthesis took place within 6 h, as judged
      by the incorporation of [3H]uracil. A group of proteins were found to be
      specifically synthesized during an early stage of germination. In addition, a new
      major spore-associated protein with a size of 41.5 kDa became detectable in the
      spore shell fraction 3 h after germination. The present results demonstrate that
      myxospore germination occurs in at least two steps: the loss of myxospore
      refractility, followed by an outburst of metabolic activities. The first step can
      occur even in the absence of energy metabolism, while the second step was blocked
      by rifampin, EGTA, and protease inhibitors.

PMID- 7635814
TI  - Suppression of the Fix- phenotype of Rhizobium meliloti exoB mutants by lpsZ is
      correlated to a modified expression of the K polysaccharide.
AB  - The rhizobial production of extracellular polysaccharide (EPS) is generally
      required for the symbiotic infection of host plants that form nodules with an
      apical meristem (indeterminate nodules). One exception is Rhizobium meliloti
      AK631, an exoB mutant of Rm41, which is deficient in EPS production yet infects
      and fixes nitrogen (i.e., is Fix+) on alfalfa, an indeterminate nodule-forming
      plant. A mutation of lpsZ in AK631 results in a Fix- strain with altered phage
      sensitivity, suggesting that a cell surface factor may substitute for EPS in the
      alfalfa-AK631 symbiosis. Biochemical analyses of the cell-associated
      polysaccharides of AK631 and Rm5830 (AK631 lpsZ) demonstrated that the lpsZ
      mutation affected the expression of a surface polysaccharide that is analogous to
      the group II K polysaccharides of Escherichia coli; the polysaccharide contains 3
      deoxy-D-manno-2-octulosonic acid or a derivative thereof in each repeating unit.
      Rm5830 produced a polysaccharide with altered chromatographic and electrophoretic
      properties, indicating a difference in the molecular weight range. Similar
      results were obtained in a study of Rm1021, a wild-type isolate that lacks the
      lpsZ gene: the introduction of lpsZ into Rm1021 exoB (Rm6903) both suppresses the
      Fix- phenotype and results in a modified expression of the K polysaccharide.
      Chromatography and electrophoresis analysis showed that the polysaccharide
      extracted from Rm6903 lpsZ+ differed from that of Rm6903 in molecular weight
      range. Importantly, the effect of LpsZ is not structurally specific, as the
      introduction lpsZ+ into Rhizobium fredii USDA257 also resulted in a molecular
      weight range change in the structurally distinct K polysaccharide produced by
      that strain. This evidence suggests that LpsZ has a general effect on the size
      specific expression of rhizobial K polysaccharides.

PMID- 7635812
TI  - Genetic structure of the dnaA region of the cyanobacterium Synechocystis sp.
      strain PCC6803.
AB  - We have cloned and sequenced the dnaA region of Synechocystis sp. strain PCC6803,
      a bacterium with a light-dependent cell cycle. The dnaA gene product, DnaA, is
      the central factor for replication initiation in bacteria. The deduced amino acid
      sequence of the protein encoded by the cyanobacterial dnaA gene is 45% identical
      to DnaA of Bacillus subtilis and fits very well into the homology pattern of the
      known eubacterial DnaA proteins. The genetic environment of the Synechocystis sp.
      strain PCC6803 dnaA gene is completely different from the one in other
      eubacteria. An open reading frame of unknown function, orf134, was detected
      upstream of dnaA. The purT gene homolog encoding the glycinamide ribonucleotide
      transformylase T starts about 200 bp away from this open reading frame in the
      opposite direction. Downstream of the dnaA gene we detected the start of the
      psbDC operon, which codes for the photosystem II reaction center proteins D2 and
      CP43 that are involved in the positioning of chlorophyll a.

PMID- 7635815
TI  - Salmonella typhimurium pgtB mutants conferring constitutive expression of
      phosphoglycerate transporter pgtP independent of pgtC.
AB  - PgtC is one of the three components of the atypical "two-component" pgt
      regulatory system. To investigate whether functional PgtC required for the
      induction of pgtP expression could be bypassed in the signal transduction
      process, we sought, and succeeded in isolating, intergenic suppressors arising in
      the low-copy mini-F plasmid, pSJ11, bearing the entire pgt system except for a
      168-bp deletion near the end of the pgtC gene. By transport assays, these
      suppressors were found to confer constitutive pgtP expression. Intriguingly, all
      five mutations reside near the 5' end of the pgtB gene, at codons 19 and 21. One
      mutation alters Arg-19 to Gln, two alter Ala-21 to Thr, one alters Ala-21 to Val,
      and one alters Ala-21 to Ile. Appropriate strains in which the pgtP promoter was
      fused to lacZ and which bore the pgtB mutations with and without mutations in
      pgtC and pgtA genes were constructed, and the epistatic relationships of the wild
      type pgtC allele, a mutant pgtA allele, and an essentially total deletion of pgtC
      to the constitutive pgtB mutations were determined. In the mutant strains bearing
      the Ala-21 --> Ile and Ala-21 --> Val substitutions, the level of constitutive
      pgtP-lacZ reporter expression was not affected by the presence of the wild-type
      pgtC allele, nor was it affected by the total absence of PgtC in the case of the
      Ala-21 --> Val alteration examined; however, in the mutant strains bearing the
      Ala-21 --> Thr and the Arg-19 --> Gln substitutions, the extent of constitutive
      pgtP-lacZ reporter expression was markedly enhanced by the presence of wild-type
      pgtC allele and, in the case of the Arg-19 -->Gln change examined, by the total
      absence of PgtC as well. These results indicate that PgtC contains no domain
      necessary for the kinase activity; that PgtB can be activated in the absence of
      PgtC mutational alterations of the protein itself; and that PgtB and PgtC
      interact in the signaling process, with PgtC functioning to activate and modulate
      the kinase activity of Pgtb. In all strains, the replacement of the wild type
      pgtA allele with a mutant pgtA allele completely abolished expression of the pgtP
      lacZ reporter, indicating that functional pgtA is essential for the
      constitutivity. His-457 of PgtB, a potential site of autophosphorylation, is also
      required for the constitutivity because its change to Val drastically reduced
      pgtP-lacZ reporter expression. The structural basis for the activation of the
      altered PgtB is discussed in terms of putative structure of PgtB in the membrane.

PMID- 7635816
TI  - Contribution of gentamicin 2'-N-acetyltransferase to the O acetylation of
      peptidoglycan in Providencia stuartii.
AB  - A collection of Providencia stuartii mutants which either underexpress or
      overexpress aac(2')-Ia, the chromosomal gene coding for gentamicin 2'-N
      acetyltransferase (EC 2.3.1.59), have been characterized phenotypically as
      possessing either lower or higher levels of peptidoglycan O acetylation,
      respectively, than the wild type. These mutants were subjected to both negative
      staining and thin-section electron microscopy. P. stuartii PR100, with 42% O
      acetylation of peptidoglycan compared with 52% O acetylation in the wild type,
      appeared as irregular rods. In direct contrast, P. stuartii strains PR50.LM3 and
      PR51, with increased levels of peptidoglycan O acetylation (65 and 63%,
      respectively), appeared as coccobacilli and chain formers, respectively. Membrane
      blebbing was also observed with the chain-forming strain PR51. Thin sectioning of
      this mutant indicated that it was capable of proper constriction and separation.
      P. stuartii PM1, when grown to mid-exponential phase, did not have altered
      peptidoglycan O-acetylation levels, and cellular morphology remained similar to
      that of wild-type strains. However, continued growth into stationary phase
      resulted in a 15% increase in peptidoglycan O acetylation concomitant with a
      change of some cells from a rod-shaped to a coccobacillus-shaped morphology. The
      fact that these apparent morphological changes were directly related to levels of
      O acetylation support the view that this modification plays a role in the
      maintenance of peptidoglycan structure, presumably through the control of
      autolytic activity.

PMID- 7635817
TI  - Escherichia coli genes required for cytochrome c maturation.
AB  - The so-called aeg-46.5 region of Escherichia coli contains genes whose expression
      is induced under anaerobic growth conditions in the presence of nitrate or
      nitrite as the terminal electron acceptor. In this work, we have examined more
      closely several genes of this cluster, here designated ccmABCDEFGH, that are
      homologous to two separate Bradyrhizobium japonicum gene clusters required for
      the biogenesis of c-type cytochromes. A deletion mutant of E. coli which lacked
      all of these genes was constructed. Maturation of indigenous c-type cytochromes
      synthesized under anaerobic respiratory conditions, with nitrite, nitrate, or
      trimethylamine N-oxide as the electron acceptor, was found to be defective in the
      mutant. The biogenesis of foreign cytochromes, such as the soluble B. japonicum
      cytochrome c550 and the membrane-bound Bacillus subtilis cytochrome c550, was
      also investigated. None of these cytochromes was synthesized in its mature form
      when expressed in the mutant, as opposed to the situation in the wild type. The
      results suggest that the E. coli ccm gene cluster present in the aeg-46.5 region
      is required for a general pathway involved in cytochrome c maturation.

PMID- 7635819
TI  - Amino acid efflux in response to chemotactic and osmotic signals in Bacillus
      subtilis.
AB  - We observed a large efflux of nonvolatile radioactivity from Bacillus subtilis in
      response to the addition of 31 mM butyrate or the withdrawal of 0.1 M aspartate
      in a flow assay. The major nonvolatile components effluxed were methionine,
      proline, histidine, and lysine. In studies of the release of volatile
      radioactivity in chemotaxis by B. subtilis cells that had been labeled with
      [3H]methionine, the breakdown of methionine to methanethiol can contribute
      substantially to the volatile radioactivity in fractions following addition of
      0.1 M aspartate. However, methanol was confirmed to be released after aspartate
      addition and, in lesser quantities, after aspartate withdrawal. Methanol and
      methanethiol were positively identified by derivitization with 3,5-dinitro
      benzoylchloride. Amino acid efflux but not methanol release was observed in
      response to 0.1 M aspartate stimulation of a cheR mutant of B. subtilis that
      lacks the chemotaxis methylesterase. The amino acid efflux could be reproduced by
      withdrawal of 0.1 M NaCl, 0.2 M sucrose, or 0.2 M xylitol and is probably the
      result of changes in osmolarity. Chemotaxis to 10 mM alanine or 10 mM proline
      resulted in methanol release but not efflux of amino acids. In behavioral
      studies, B. subtilis tumbled for 16 to 18 s in response to a 200 mosM upshift and
      for 14 s after a 20 mosM downshift in osmolarity when the bacteria were in
      perfusion buffer (40 mosM). The pattern of methanol release was similar to that
      observed in chemotaxis. This is consistent with osmotaxis in B. subtilis away
      from an increase or decrease in the osmolarity of the incubation medium. The
      release of methanol suggests that osmotaxis is correlated with methylation of a
      methyl-accepting chemotaxis protein.

PMID- 7635818
TI  - Domain structure of phage P4 alpha protein deduced by mutational analysis.
AB  - Bacteriophage P4 DNA replication depends on the product of the alpha gene, which
      has origin recognition ability, DNA helicase activity, and DNA primase activity.
      One temperature-sensitive and four amber mutations that eliminate DNA replication
      in vivo were sequenced and located in the alpha gene. Sequence analysis of the
      entire gene predicted a domain structure for the alpha polypeptide chain (777
      amino acid residues, M(r) 84,900), with the N terminus providing the catalytic
      activity for the primase and the middle part providing that for the
      helicase/nucleoside triphosphatase. This model was confirmed experimentally in
      vivo and in vitro. In addition, the ori DNA recognition ability was found to be
      associated with the C-terminal third of the alpha polypeptide chain. The type A
      nucleotide-binding site is required for P4 replication in vivo, as shown for
      alpha mutations at G-506 and K-507. In the absence of an active DnaG protein, the
      primase function is also essential for P4 replication. Primase-null and helicase
      null mutants retain the two remaining activities functionally in vitro and in
      vivo. The latter was demonstrated by trans complementation studies, indicating
      the assembly of active P4 replisomes by a primase-null and a helicase-null
      mutant.

PMID- 7635820
TI  - Characterization of the functional sites in the oriT region involved in DNA
      transfer promoted by sex factor plasmid R100.
AB  - We have previously identified three sites, named sbi, ihfA, and sbyA,
      specifically recognized or bound by the TraI, IHF, and TraY proteins,
      respectively; these sites are involved in nicking at the origin of transfer,
      oriT, of plasmid R100. In the region next to these sites, there exists the sbm
      region, which consists of four sites, sbmA, sbmB, sbmC, and sbmD; this region is
      specifically bound by the TraM protein, which is required for DNA transfer.
      Between sbmB and sbmC in this region, there exists another IHF-binding site,
      ihfB. The region containing all of these sites is located in the proximity of the
      tra region and is referred to as the oriT region. To determine whether these
      sites are important for DNA transfer in vivo, we constructed plasmids with
      various mutations in the oriT region and tested their mobilization in the
      presence of R100-1, a transfer-proficient mutant of R100. Plasmids with either
      deletions in the sbi-ihfA-sbyA region or substitution mutations introduced into
      each specific site in this region were mobilized at a greatly reduced frequency,
      showing that all of these sites are essential for DNA transfer. By binding to
      ihfA, IHF, which is known to bend DNA, may be involved in the formation of a
      complex (which may be called oriT-some) consisting of TraI, IHF, and TraY that
      efficiently introduces a nick at oriT. Plasmids with either deletions in the sbm
      ihfB region or substitution mutations introduced into each specific site in this
      region were mobilized at a reduced frequency, showing that this region is also
      important for DNA transfer. By binding to ihfB, IHF may also be involved in the
      formation of another complex (which may be called the TraM-IHF complex)
      consisting of TraM and IHF that ensures DNA transfer with a high level of
      efficiency. Several-base-pair insertions into the positions between sbyA and sbmA
      affected the frequency of transfer in a manner dependent upon the number of base
      pairs, indicating that the phasing between sbyA and sbmA is important. This in
      turn suggests that both oriT-some and the TraM-IHF complex should be in an
      appropriate position spatially to facilitate DNA transfer.

PMID- 7635821
TI  - Comparison of a fungal (family I) and bacterial (family II) cellulose-binding
      domain.
AB  - A family II cellulose-binding domain (CBD) of an exoglucanase/xylanase (Cex) from
      the bacterium Cellulomonas fimi was replaced with the family I CBD of
      cellobiohydrolase I (CbhI) from the fungus Trichoderma reesei. Expression of the
      hybrid gene in Escherichia coli yielded up to 50 mg of the hybrid protein,
      CexCBDCbhI, per liter of culture supernatant. The hybrid was purified to
      homogeneity by affinity chromatography on cellulose. The relative association
      constants (Kr) for the binding of Cex, CexCBDCbhI, the catalytic domain of Cex
      (p33), and CbhI to bacterial microcrystalline cellulose (BMCC) were 14.9, 7.8,
      0.8, and 10.6 liters g-1, respectively. Cex and CexCBDCbhI had similar substrate
      specificities and similar activities on crystalline and amorphous cellulose. Both
      released predominantly cellobiose and cellotriose from amorphous cellulose.
      CexCBDCbhI was two to three times less active than Cex on BMCC, but significantly
      more active than Cex on soluble cellulose and on xylan. Unlike Cex, the hybrid
      protein neither bound to alpha-chitin nor released small particles from dewaxed
      cotton fibers.

PMID- 7635822
TI  - Host growth temperature and a conservative amino acid substitution in the
      replication protein of pPS10 influence plasmid host range.
AB  - pPS10 is a replicon isolated from Pseudomonas syringe pv. savastanoi that can be
      established at 37 degrees C efficiently in Pseudomonas aeruginosa but very
      inefficiently in Escherichia coli. The establishment of the wild-type pPS10
      replicon in E. coli is favored at low temperatures (30 degrees C or below). RepA
      protein of pPS10 promotes in vitro plasmid replication in extracts from E. coli,
      and this replication depends on host proteins DnaA, DnaB, DnaG, and SSB. Mutant
      plasmids able to efficiently replicate in E. coli at 37 degrees C were obtained.
      Three of four mutants whose mutations were mapped show a conservative Ala-->Val
      change in the amino-terminal region of the replication protein RepA. Plasmids
      carrying this mutation maintain the capacity to replicate in P. aeruginosa and
      have a fourfold increase in copy number in this host. The mutation does not
      substantially alter the autoregulation mediated by RepA. These results show that
      the physiological conditions of the host as well as subtle changes in the plasmid
      replication protein can modulate the host range of the pPS10 replicon.

PMID- 7635823
TI  - Differential DNA secondary structure-mediated deletion mutation in the leading
      and lagging strands.
AB  - The frequencies of deletion of short sequences (mutation inserts) inserted into
      the chloramphenicol acetyl-transferase (CAT) gene were measured for pBR325 and
      pBR523, in which the orientation of the CAT gene was reversed, in Escherichia
      coli. Reversal of the CAT gene changes the relationship between the transcribed
      strand and the leading and lagging strands of the DNA replication fork in pBR325
      based plasmids. Deletion of these mutation inserts may be mediated by slipped
      misalignment during DNA replication. Symmetrical sequences, in which the same
      potential DNA structural misalignment can form in both the leading and lagging
      strands, exhibited an approximately twofold difference in the deletion
      frequencies upon reversal of the CAT gene. Sequences that contained an inverted
      repeat that was asymmetric with respect to flanking direct repeats were designed.
      With asymmetric mutation inserts, different misaligned structural intermediates
      could form in the leading and lagging strands, depending on the orientation of
      the insert and/or of the CAT gene. When slippage could be stabilized by a hairpin
      in the lagging strand, thereby forming a three-way junction, deletion occurred by
      up to 50-fold more frequently than when this structure formed in the leading
      strand. These results support the model that slipped misalignment involving DNA
      secondary structure occurs preferentially in the lagging strand during DNA
      replication.

PMID- 7635825
TI  - Molecular dissection of mutations in the Bacillus subtilis spore photoproduct
      lyase gene which affect repair of spore DNA damage caused by UV radiation.
AB  - In response to UV irradiation, Bacillus subtilis spore DNA accumulates the unique
      thymine dimer 5-thyminyl-5,6-dihydrothymine, or spore photoproduct (SP). SP is
      broken down into monomers during spore germination by the product of the spl gene
      which has been proposed to encode the enzyme SP lyase. The wild-type spl gene was
      cloned by complementation of a mutation designated spl-1; the putative spl gene
      product is a 40-kDa protein whose deduced amino acid sequence contains regions
      homologous to DNA photolyases. During phenotypic characterization of spl
      subclones using transformation crosses between the cloned wild-type spl gene and
      an spl-1 mutant recipient, in addition to the expected transformant classes
      exhibiting UV-resistant (type I) and UV-sensitive (type III) spores, an
      additional recombinant class was observed (called type II), spores of which
      exhibited slower germination kinetics following UV irradiation. The results
      suggested that the spl-1 allele consisted of at least two separable mutations.
      The DNA region which could rescue the spl-1 allele was localized to a 511-bp
      region within the spl coding sequence; this region was amplified from the spl-1
      mutant chromosome by PCR and sequenced. The region contained two amino acid
      substitutions, an Arg replacing Gly-168 (G168R) and an Asp replacing Gly-242
      (G242D) in the deduced SP lyase sequence, as well as 18 silent mutations. PCR
      amplification of chromosomal DNA from a selected type II recombinant and sequence
      analysis of the amplification product confirmed that recombination had indeed
      occurred between codons 168 and 242 and further localized the point of crossover
      by using the 18 silent mutations as molecular markers throughout the region. By
      in vitro mutagenesis, alleles of spl containing all combinations of single and
      double amino acid substitutions were introduced into the cloned wild-type spl
      gene. When integrated into the B. subtilis chromosome at the amyE locus, it was
      observed that although both amino acid substitutions contribute to the spl-1
      phenotype, the G168R mutation exerted a much greater effect than did the G242D
      mutation.

PMID- 7635824
TI  - Biochemical and molecular characterization of the oxidative branch of glycerol
      utilization by Citrobacter freundii.
AB  - Glycerol dehydrogenase (EC 1.1.1.6) and dihydroxyacetone kinase (EC 2.7.1.29)
      were purified from Citrobacter freundii. The dehydrogenase is a hexamer of a
      polypeptide of 43,000 Da. The enzyme exhibited a rather broad substrate
      specificity, but glycerol was the preferred substrate in the physiological
      direction. The apparent Kms of the enzyme for glycerol and NAD+ were 1.27 mM and
      57 microM, respectively. The kinase is a dimer of a polypeptide of 57,000 Da. The
      enzyme was highly specific for the substrates dihydroxyacetone and ATP; the
      apparent Kms were 30 and 70 microM, respectively. The DNA region which contained
      the genes encoding glycerol dehydrogenase (dhaD) and dihydroxyacetone kinase
      (dhaK) was cloned and sequenced. Both genes were identified by N-terminal
      sequence comparison. The deduced dhaD gene product (365 amino acids) exhibited
      high degrees of homology to glycerol dehydrogenases from other organisms and less
      homology to type III alcohol dehydrogenases, whereas the dhaK gene product (552
      amino acids) revealed no significant homology to any other protein in the
      databases. A large gene (dhaR) of 1,929 bp was found downstream from dhaD. The
      deduced gene product (641 amino acids) showed significant similarities to members
      of the sigma 54 bacterial enhancer-binding protein family.

PMID- 7635826
TI  - Involvement of the "A" isozyme of methyltransferase II and the 29-kilodalton
      corrinoid protein in methanogenesis from monomethylamine.
AB  - An assay which allowed detection of proteins involved in the trimethylamine- or
      monomethylamine (MMA)-dependent methylation of coenzyme M (CoM) was developed.
      The two activities could be separated by anion-exchange chromatography. The
      unresolved activity responsible for MMA:CoM methyl transfer eluted from a gel
      permeation column in the molecular mass range of 32 kDa. The activity was
      purified to two monomeric proteins of 40 and 29 kDa. The preparation contained
      protein-bound corrinoid in a mixture of Co(II) and Co(III) states, as well as
      methyl-B12:CoM methyltransferase (MT2) activity. N-terminal sequence analysis
      demonstrated that the polypeptides were two previously identified proteins of
      undefined physiological function. The smaller polypeptide was the monomeric 29
      kDa corrinoid protein. The larger polypeptide was the "A" isozyme of MT2.
      Individually purified preparations of both proteins increased the rate of MMA
      dependent CoM methylation by approximately 1.7 mumol/min/mg of purified protein
      above background activity in the extract of methanol-grown cells. These results
      indicate that the 29-kDa corrinoid protein and the "A" isozyme of MT2 function in
      methanogenesis from MMA. A likely mechanism is that the 29-kDa corrinoid is
      methylated by MMA and the methyl group is then transferred by the "A" isozyme of
      MT2 to CoM.

PMID- 7635827
TI  - A multicopy plasmid of the extremely thermophilic archaeon Sulfolobus effects its
      transfer to recipients by mating.
AB  - A plasmid of 45 kb, designated pNOB8, was found in high copy number in a new
      heterotrophic Sulfolobus isolate, NOB8H2, from Japan. Dissemination of the
      plasmid occurred in six cultures of nine different Sulfolobus strains when small
      amounts of the donor were added. These mixed cultures exhibited a high average
      copy number of the plasmid, between 20 and 40 per chromosome, and showed a marked
      growth retardation. Horizontal transfer of pNOB8 was proved by isolating
      transcipients from mating mixtures via single colonies. In these isolates, the
      copy number of the plasmid appeared to be subject to a control mechanism. Cell
      free filtrates of donor cultures did not transmit the plasmid, and plating of the
      donor on lawns of recipients did not result in plaque formation, suggesting that
      the transfer was not mediated by a virus. Rapid formation of cell-to-cell
      contacts between differently stained donor and recipient partners was
      demonstrated after the two strains were mixed. Electron microscopic analysis of
      mating mixtures revealed many cell aggregates made up of 2 to 30 cells and
      intercellular cytoplasmic bridges connecting two or more cells. Cells that had
      been transformed with purified plasmid DNA as well as transcipients isolated from
      mating mixtures were shown to serve as donors for further transmission of pNOB8.
      The plasmid undergoes extensive genetic variations, since deletions and
      insertions were frequently observed in plasmid preparations from the donor strain
      and from mating mixtures.

PMID- 7635828
TI  - Analyses of the DNA-binding and transcriptional activation properties of ExsA,
      the transcriptional activator of the Pseudomonas aeruginosa exoenzyme S regulon.
AB  - ExsA has been implicated as a central regulator of exoenzyme S production by
      Pseudomonas aeruginosa. In this study, the DNA-binding and transcriptional
      activation properties of ExsA were investigated. ExsA was produced and purified
      as a fusion protein, MALA3A2, which was shown to bind specifically to promoter
      regions that regulated transcription of the exoenzyme S trans-regulatory locus
      (pC) and a locus located directly downstream of exsA (pD). Previously, MALA3A2
      was shown to bind the exoS 5' PstI-NsiI region, which contained two independent
      but coordinately regulated (ExsA-mediated) promoters, pS' (now termed pORF1) and
      pS. DNase I footprint analysis of the promoter regions bound by ExsA revealed a
      common protected consensus sequence of TXAAAAXA. The consensus sequence was
      located -51 to -52 bp upstream of the transcriptional start sites for pD, pS, and
      pORF1. Promoter fusion, DNA-binding, and mutagenesis analysis indicated that the
      consensus sequence was important for transcriptional activation. Each ExsA
      controlled promoter region contained at least two consensus sites in close
      proximity, similar to the arrangement of half-sites seen in AraC-controlled
      (Escherichia coli) or VirF-controlled (Yersinia enterocolitica) promoters.
      However, the results of this study suggested that only one consensus site was
      required in the exoenzyme S (pS) or ORF1 promoter (pORF1) to initiate
      transcription. These data suggest that members of the exoenzyme S regulon can be
      defined as possessing an ExsA consensus element which maps at bp -51 or -52
      relative to the transcriptional start site.

PMID- 7635829
TI  - The genes involved in cytokinin biosynthesis in Erwinia herbicola pv.
      gypsophilae: characterization and role in gall formation.
AB  - A locus conferring cytokinin production was previously isolated from the gall
      forming bacterium Erwinia herbicola pv. gypsophilae. This locus resided in a
      cluster with the genes specifying indole-3-acetic acid production on the
      pathogenicity-associated plasmid pPATH (A. Lichter, S. Manulis, O. Sagee, Y.
      Gafni, J. Gray, R. Meilen, R. O. Morris, and I. Barash, Mol. Plant Microbe
      Interact., 8:114-121, 1995). Sequence analysis of this locus indicated the
      presence of a cytokinin biosynthesis gene (etz) homologous to other described
      cytokinin biosynthesis genes. A unique open reading frame (pre-etz) encoding 169
      amino acids preceded etz and together with etz formed a region with a distinctive
      low G+C content. Northern (RNA) analysis indicated the presence of an etz
      specific transcript of 1 kb and a common transcript for pre-etz and etz of 1.4
      kb. The level of the 1-kb transcript was high in the late logarithmic phase and
      very low in the stationary phase. In contrast, the level of the 1.4-kb transcript
      was lower than that of the 1-kb transcript in the late logarithmic phase and
      predominant in the stationary phase. A marker exchange mutant of etz which did
      not produce cytokinins exhibited a reduction in gall size on Gypsophila cuttings
      and almost abolished disease symptoms in a whole-plant assay. Complementation of
      this marker exchange mutant with the intact etz gene on a multicopy plasmid
      resulted in overproduction of cytokinins and larger plant galls from which small
      shoots emerged. Insertional mutation in pre-etz resulted in a sharp decrease in
      both the level of the etz-specific transcript and cytokinin production. A
      frameshift mutation in pre-etz caused a similar reduction in the cytokinin level.
      A marker exchange mutation in pre-etz caused a reduction of symptoms but to lower
      degree than the etz mutation. In the former mutant, cytokinin production and
      pathogenicity could not be restored by complementation. Furthermore, attempts to
      complement the etz marker exchange mutant with a plasmid containing an intact etz
      gene and a frameshift mutation in the pre-etz gene were unsuccessful. These
      results suggest that the mutations in pre-etz were trans dominant.

PMID- 7635830
TI  - Characterization and DNA sequence of the mobilization region of pLV22a from
      Bacteroides fragilis.
AB  - A 4.2-kb plasmid (pLV22a) native to Bacteroides fragilis LV22 became fused to a
      transfer-deficient Bacteroides spp.-Escherichia coli shuttle vector by an inverse
      transposition event, resulting in a transferrable phenotype. The transfer
      phenotype was attributable to pLV22a, which was also capable of mobilization
      within E. coli when coresident with the IncP beta R751 plasmid. Transposon
      mutagenesis with Tn1000 localized the mobilization region to a 1.5-kb DNA segment
      in pLV22a. The mobilization region has been sequenced, and five open reading
      frames have been identified. Mutants carrying disruptions in any of the three
      genes designated mbpA, mbpB, and mbpC and coding for deduced products of 11.3,
      30.4, and 17.1 kDa, respectively, cannot be mobilized when coresident with R751.
      Mutations in all three genes can be complemented in the presence of the
      respective wild-type genes, indicating that the products of mbpA, mbpB, and mbpC
      have roles in the mobilization process and function in trans. The deduced 30.4
      kDa MbpB protein contains a 14-amino-acid conserved motif that is also found in
      the DNA relaxases of a variety of conjugal and mobilizable plasmids and the
      conjugative transposon Tn4399. Deletion analysis and complementation experiments
      have localized a cis-acting region of pLV22a within mbpA.

PMID- 7635831
TI  - Identification and sequence analysis of genes involved in late steps in cobalamin
      (vitamin B12) synthesis in Rhodobacter capsulatus.
AB  - A 6.4-kb region of a 6.8-kb BamHI fragment carrying Rhodobacter capsulatus genes
      involved in late steps of cobalamin synthesis has been sequenced. The nucleotide
      sequence and genetic analysis revealed that this fragment contains eight genes
      arranged in at least three operons. Five of these eight genes show homology to
      genes involved in the cobalamin synthesis of Pseudomonas denitrificans and
      Salmonella typhimurium. The arrangement of these homologous genes differs
      considerably in the three genera. Upstream of five overlapping genes (named
      bluFEDCB), a promoter activity could be detected by using lacZ fusions. This
      promoter shows no regulation by oxygen, vitamin B12 (cobalamin), or cobinamide.
      Disruption of the bluE gene by a Tn5 insertion (strain AH2) results in reduced
      expression of the puf and puc operons, which encode pigment-binding proteins of
      the photosynthetic apparatus. The mutant strain AH2 can be corrected to a wild
      type-like phenotype by addition of vitamin B12 or cobinamide dicyanide.
      Disruption of the bluB gene by an interposon (strain BB1) also disturbs the
      formation of the photosynthetic apparatus. The mutation of strain BB1 can be
      corrected by vitamin B12 but not by cobinamide. We propose that a lack of
      cobalamin results in deregulation and a decreased formation of the photosynthetic
      apparatus.

PMID- 7635832
TI  - Phosphate concentration regulates transcription of the Acinetobacter
      polyhydroxyalkanoic acid biosynthetic genes.
AB  - The polyhydroxyalkanoic acid (PHA) biosynthetic gene locus was cloned and
      characterized from an Acinetobacter sp. isolated from activated sludge.
      Nucleotide sequence analysis identified three clustered genes, phaAAc (encoding a
      beta-ketothiolase), phaBAc (encoding an acetoacetyl coenzyme A reductase), and
      phaCAc (encoding a PHA synthase). In addition, an open reading frame (ORF1) with
      potential to encode a 13-kDa protein was identified within this locus. The
      sequence of the putative translational product of ORF1 does not show significant
      similarity to any sequences in the database. A plasmid containing the
      Acinetobacter pha locus conferred the ability to accumulate poly-beta
      hydroxybutyrate on its Escherichia coli host. These genes appear to lie in an
      operon transcribed by two promoters upstream of phaBAc, an apparent constitutive
      promoter, and a second promoter induced by phosphate starvation and under pho
      regulon control. These as well as a number of additional potential transcription
      start points were identified by a combination of primer extension and promoter
      chloramphenicol acetyltransferase gene fusion studies carried out in
      Acinetobacter or E. coli transformants.

PMID- 7635833
TI  - Fine-structure deletion analysis of the transcriptional silencer of the proU
      operon of Salmonella typhimurium.
AB  - Transcriptional control of the osmotically regulated proU operon of Salmonella
      typhimurium is mediated in part by a transcriptional silencer downstream from the
      promoter (D.G. Overdier and L.N. Csonka, Proc. Natl. Acad. Sci. USA 89:3140-3144,
      1992). We carried out a fine-structure deletion analysis to determine the
      structure and the position of the silencer, which demonstrated that this
      regulatory element is located between nucleotide positions +73 to +274 downstream
      from the transcription start site. The silencer appears to be made up of a number
      of components which have cumulative negative regulatory effects. Deletions or
      insertions of short nucleotide sequences (< 40 bp) between the proU promoter and
      the silencer do not disrupt repression exerted by the silencer, but long
      insertions (> or = 0.8 kbp) result in a high level of expression from the proU
      promoter, similar to that imparted by deletion of the entire silencer. The
      general DNA-binding protein H-NS is required for the full range of repression of
      the proU operon in media of low osmolality. Although in the presence of the
      silencer hns mutations increased basal expression from the proU promoter three-
      to sixfold, in the absence of the silencer they did not result in a substantial
      increase in basal expression from the proU promoter. Furthermore, deletion of the
      silencer in hns+ background was up to 10-fold more effective in increasing basal
      expression from the proU promoter than the hns mutations. These results indicate
      that osmotic control of the proU operon is dependent of some factor besides H-NS.
      We propose that the transcriptional regulation of this operon is effected in
      media of low osmolality by a protein which makes the promoter inaccessible to RNA
      polymerase by forming a complex containing the proU promoter and silencer.

PMID- 7635834
TI  - Different internal metabolites trigger the induction of glycolytic gene
      expression in Saccharomyces cerevisiae.
AB  - In the yeast Saccharomyces cerevisiae, the sugar-induced expression of various
      genes coding for glycolytic enzymes is triggered by increases in the
      concentrations of different internal metabolites. Here, we show that the
      induction of the glycolytic isoenzyme enolase 2 is strictly dependent on the
      abilities of different mutant strains to increase the level of glucose-6
      phosphate after the addition of sugars. In contrast, the induction of alcohol
      dehydrogenase I is dependent on increasing concentrations of metabolites in the
      late stages of glycolysis.

PMID- 7635835
TI  - Involvement of cysB and cysE genes in the sensitivity of Salmonella typhimurium
      to mecillinam.
AB  - cysB and cysE strains were obtained as spontaneous mecillinam-resistant mutants
      of Salmonella typhimurium. The resistance to mecillinam was caused by the cys
      mutations which also conferred tolerance to lethal cell shape mutations. Most,
      but not all, cysB and cysE mutations from other origins displayed the same
      behavior. Resistance was abolished by O- and N-acetylserine in cysE mutants; by
      thiosulfate, sulfite, and sulfide in cysB mutants; and by cysteine in both types
      of mutants. It is concluded that an event involved in mecillinam action requires
      the inducer and the activator protein of the cysteine regulon.

PMID- 7635836
TI  - Interruption of the ferredoxin (flavodoxin) NADP+ oxidoreductase gene of
      Escherichia coli does not affect anaerobic growth but increases sensitivity to
      paraquat.
AB  - Ferredoxin (flavodoxin) NADP+ oxidoreductase participates in methionine
      biosynthesis and in the function of two anaerobic enzymes, pyruvate formate-lyase
      and ribonucleotide reductase. We prepared insertion mutants of Escherichia coli
      lacking a functional enzyme. They do not require methionine and they grow well
      anaerobically, but they show increased sensitivity to paraquat.

PMID- 7635837
TI  - In vitro binding affinity of the Bacillus subtilis AbrB protein to six different
      DNA target regions.
AB  - AbrB is a transcriptional regulator of many Bacillus subtilis genes. A number of
      AbrB-binding sites have previously been delimited by DNase I footprinting
      studies, but the heterogeneity of the protected sequences and sizes has not led
      to a determination of a possible consensus motif for recognition. We have
      examined the affinity of AbrB for binding to six known target regions when the
      regions were placed in DNA fragments of various sizes. The sites are shown to
      vary dramatically in AbrB-binding affinity when they are present in smaller
      fragments, but the differences are smaller when the affinities of larger
      fragments are compared. Additional observations that indicate that AbrB binding
      may be a multistep cooperative process are reported.

PMID- 7635838
TI  - Physical mapping and characterization of a catabolic plasmid from the deep
      subsurface bacterium Sphingomonas sp. strain F199.
AB  - A supercoiled 180-kb plasmid, pNL1, has been isolated from the deep-subsurface,
      chemoheterotrophic Sphingomonas sp. strain F199, and a physical map was
      generated. Analysis of a pNL1-derived cosmid library indicated that catechol 2,3
      dioxygenase activity was linked to two distinct regions of the plasmid. Thus, the
      genes for aromatic catabolism in this Sphingomonas strain are, at least in part,
      plasmid encoded.

PMID- 7635839
TI  - Molecular cloning of the pyrE gene from the extreme thermophile Thermus flavus.
AB  - Mutants of the extreme thermophile Thermus flavus in the pyrimidine biosynthetic
      pathway (Pyr-) were isolated by resistance to 5-fluoroorotic acid. The pyrE gene,
      which codes for the orotate phosphoribosyltransferase, was cloned by
      recombination with one of the isolated Pyr- T. flavus mutant strains. It was
      subcloned by complementation of an Escherichia coli pyrE mutant strain and was
      sequenced. The deduced polypeptide sequence extends over 183 amino acids. Several
      independent Pyr- mutations were mapped within the pyrE locus by recombination
      with fragments of the cloned gene.

PMID- 7635840
TI  - Expression of a functional fungal polyketide synthase in the bacterium
      Streptomyces coelicolor A3(2).
AB  - The multifunctional 6-methylsalicylic acid synthase gene from Penicillium patulum
      was engineered for regulated expression in Streptomyces coelicolor. Production of
      significant amounts of 6-methylsalicylic acid by the recombinant strain was
      proven by nuclear magnetic resonance spectroscopy. These results suggest that it
      is possible to harness the molecular diversity of eukaryotic polyketide pathways
      by heterologous expression of biosynthetic genes in an easily manipulated model
      bacterial host in which prokaryotic aromatic and modular polyketide synthase
      genes are already expressed and recombined.

PMID- 7635841
TI  - Regulation of the glnBA operon of Rhodobacter capsulatus.
AB  - In a recent report identifying the promoters of the Rhodobacter capsulatus glnBA
      operon, it was suggested that an internal promoter upstream of the glnA gene
      probably resulted in different levels of glnBA and glnA transcripts (D. Foster
      Hartnett and R. G. Kranz, J. Bacteriol. 176:5171-5176, 1994). Therefore, to
      investigate the regulation, we constructed and examined the expression of a
      number of translational fusions in R. capsulatus glnBA. The results support a
      role for posttranscriptional regulation.

PMID- 7635842
TI  - Use of Tn5tac1 to clone a pel gene encoding a highly alkaline, asparagine-rich
      pectate lyase isozyme from an Erwinia chrysanthemi EC16 mutant with deletions
      affecting the major pectate lyase isozymes.
AB  - Erwinia chrysanthemi mutant CUCPB5047, delta(pelA pelE) delta(pelB pelC)::28bp
      delta(pelX) delta 4bp pehX::omega Cmr, was constructed, mutated with Tn5tac1, and
      screened for isopropyl-beta-D-thiogalactopyranoside-dependent pectate lyase (Pel)
      production. A Kmr SacI fragment from the hyperexpressing Pel+ mutant CUCPB5066
      was cloned into Escherichia coli and sequenced. The gene identified, pelL,
      encodes a novel, asparagine-rich, highly alkaline enzyme that is similar in
      primary structure to PelX and in enzymological properties to PelE.

PMID- 7635843
TI  - Tetracycline/H+ antiport and Na+/H+ antiport catalyzed by the Bacillus subtilis
      TetA(L) transporter expressed in Escherichia coli.
AB  - The properties of TetA(L)-dependent tetracycline/proton and Na+/proton antiport
      were studied in energized everted vesicles of Escherichia coli transformed with a
      cloned tetA(L) gene (pJTA1) from Bacillus subtilis. Inhibition patterns by
      valinomycin and nigericin indicated that both antiports were electrogenic, in
      contrast to the tetracycline/proton antiport encoded by gram-negative plasmid tet
      genes. Tetracycline uptake in the everted system was dependent upon a divalent
      cation, with cobalt being the preferred one. The apparent Km for tetracycline was
      markedly increased at pH 8.5 versus pH 7.5, whereas the Vmax was unchanged. The
      much higher apparent Km for Na+ decreased at pH 8.5 relative to that at pH 7.5,
      as did the Vmax. Na+ did not affect tetracycline uptake, nor did Co2+ and/or
      tetracycline affect Na+ uptake; complex patterns of inhibition by amiloride and
      analogs thereof were observed.

PMID- 7635844
TI  - Expression and characterization of UDPGlc dehydrogenase (KfiD), which is encoded
      in the type-specific region 2 of the Escherichia coli K5 capsule genes.
AB  - Region 2 of the Escherichia coli K5 capsule gene cluster contains four genes
      (kfiA through -D) which encode proteins involved in the synthesis of the K5
      polysaccharide. A DNA fragment containing kfiD was amplified by PCR and cloned
      into the gene fusion vector pGEX-2T to generate a GST-KfiD fusion protein. The
      fusion protein was isolated from the cytoplasms of IPTG (isopropyl-beta-D
      thiogalactopyranoside)-induced recombinant bacteria by affinity chromatography
      and cleaved with thrombin. The N-terminal amino acid sequence of the cleavage
      product KfiD' corresponded to the predicted amino acid sequence of KfiD with an N
      terminal glycyl-seryl extension from the cleavage site of the fusion protein.
      Anti-KfiD antibodies obtained with KfiD' were used to isolate the intact KfiD
      protein from the cytoplasms of E. coli organisms overexpressing the kfiD gene.
      The fusion protein, its cleavage product (KfiD'), and overexpressed KfiD
      converted UDPGlc to UDPGlcA. The KfiD protein could thus be characterized as a
      UDPglucose dehydrogenase.

PMID- 7635845
TI  - Chemical characterization of the ester-linked 3-hydroxy fatty acyl-containing
      lipids in Mycobacterium tuberculosis.
AB  - In a previous study (S. Alugupalli, F. Portaels, and L. Larsson, J. Bacteriol.
      176:2962-2969, 1994), we reported the occurrence of 21 3-hydroxy fatty acids (3
      OH-FAs) in the methanolysis products of different mycobacterial species. The
      present study was undertaken in order to chemically characterize the ester-linked
      complex native forms of these acids in Mycobacterium tuberculosis. Three 3-OH-FA
      containing lipids were purified by chromatography and analyzed by one- and two
      dimensional nuclear magnetic resonance spectroscopy, by fast atom bombardment
      mass spectrometry, and by various conventional chemical analysis techniques. 3-OH
      2,4,6-trimethyl-FAs were found in 2,3-diacyl trehalose and 2,3,6,6'-tetra-acyl-2'
      sulfate trehalose (sulfatide I), two specific glycolipids of the tubercle
      bacillus, explaining the specific occurrence of these fatty acids in the
      methanolysis products of virulent strains of M. tuberculosis. Straight-chain 3-OH
      FAs were localized in phosphatidyl ethanolamine but not in the other
      phospholipids, suggesting a possible role of this class of phospholipids in the
      metabolism of fatty acids in actinomycetes.

PMID- 7635846
TI  - Phosphorylation of Mycoplasma pneumoniae cytadherence-accessory proteins in cell
      extracts.
AB  - A cell-free system was used to characterize the phosphorylation of Mycoplasma
      pneumoniae proteins HMW1 and HMW2, which are involved in the adherence of this
      organism to human tracheal epithelium during infection. The pH and cation
      requirements for phosphorylation of HMW1 and HMW2 were determined, and the
      effects of glycolytic intermediates, cyclic AMP, and eukaryotic kinase
      phosphatase inhibitors and stimulators on this process were examined.
      Phosphoamino acid analysis identified serine as the major phosphate acceptor for
      both HMW1 and HMW2 in this system.

PMID- 7635848
TI  - The efficacy of fluoxetine combined with a heterocyclic antidepressant in
      treatment-resistant depression: a retrospective analysis.
AB  - BACKGROUND: Treatment-resistant depression is a common clinical challenge that
      often requires the use of innovative pharmacologic treatments. Recent reports
      suggest the efficacy of the combination of a serotonin selective reuptake
      inhibitor and a heterocyclic antidepressant (HCA) in depressed patients who fail
      monotherapy with either agent alone. We present our clinical experience with the
      use of fluoxetine combined with an HCA in a group of 25 treatment-resistant
      depressed subjects. METHOD: Twenty-five depressed subjects who failed to
      adequately respond to at least 4 weeks of open-label fluoxetine treatment (mean
      dose = 73 mg/day) had an HCA added to their fluoxetine. The dose of the HCA was
      increased to maximize efficacy and minimize side effects. Efficacy was measured
      using the 21-item Hamilton Rating Scale for Depression (HAM-D-21) score and the
      Clinical Global Impressions-Global Improvement (CGI) scale. RESULTS: Response to
      treatment was defined as a 50% or greater drop in the HAM-D-21 score and a CGI of
      either very much improved or moderately improved from the start of the HCA. Seven
      (35%) of 20 subjects who demonstrated a poor or partial response to fluoxetine
      responded when an HCA was added to the fluoxetine. Five (71%) of the responders
      had previously failed to respond to monotherapy with the HCA that they responded
      to when used with fluoxetine. Additionally, 5 subjects who demonstrated
      significant improvement with fluoxetine but who had mild, residual depressive
      symptoms experienced at least partial further improvement with the addition of an
      HCA. CONCLUSION: The results suggest that the addition of an HCA to fluoxetine
      may be an effective treatment in treatment-resistant depressed patients who have
      failed to adequately respond to monotherapy with fluoxetine. Additional
      controlled trials are warranted to further explore the efficacy of this treatment
      combination in patients who demonstrate a poor or partial response to
      monotherapy. When using this drug combination, the clinician is cautioned to
      prescribe low doses of the HCA and monitor serum levels closely since fluoxetine
      can raise serum HCA levels.

PMID- 7635847
TI  - Cloning, sequencing, and mutation of a gene for azurin in Methylobacillus
      flagellatum KT.
AB  - The gene cluster for methylamine utilization (mau genes) has been cloned from the
      obligate methylotrophic bacterium Methylobacillus flagellatum KT. Partial
      sequence data showed that the organization of these genes was similar to that
      found in Methylophilus methylotrophus W3A1-NS, including the lack of a gene for
      amicyanin, which had been thought to be the electron acceptor for methylamine
      dehydrogenase in M. flagellatum KT. However, a gene encoding azurin was
      discovered at the 3' end of the mau gene cluster, transcribed in the opposite
      orientation. A mutant with a defect in this gene showed impaired growth on
      methylamine, suggesting that azurin is involved in methylamine oxidation in M.
      flagellatum KT.

PMID- 7635849
TI  - Effects of clozapine on smoking in chronic schizophrenic outpatients.
AB  - BACKGROUND: The effects of clozapine administration on smoking were examined in
      chronic schizophrenic outpatients. METHOD: Twenty-nine of 30 schizophrenic
      outpatients enrolled in a university-affiliated Community Mental Health Center
      clozapine clinic were retrospectively surveyed by semistructured questionnaire
      regarding smoking before and after clozapine administration. RESULTS: Smokers
      comprised 62% (N = 18) of patients, and within this group, there was a
      significant decrease in reported daily cigarette use during clozapine treatment
      compared with level of use when patients had been treated with typical
      neuroleptics (1.67 +/- 1.13 vs. 1.26 +/- 0.72 packs/day, p = .025). CONCLUSION:
      Clozapine may alter smoking behaviors in chronic schizophrenics.

PMID- 7635850
TI  - Late-onset Tay-Sachs disease presenting as catatonic schizophrenia: diagnostic
      and treatment issues.
AB  - BACKGROUND: It is not commonly appreciated that patients with hexosaminidase A
      deficiency (Tay-Sachs disease) can first present in adulthood with psychiatric
      illness. METHOD: A 17-year-old non-Jewish male patient was referred with a
      history of treatment-resistant catatonic schizophrenia. We uncovered coexistent
      neurologic abnormalities and evidence of cognitive decline. Metabolic screening
      revealed a severe deficiency of beta-hexosaminidase A. We reviewed the literature
      on late-onset gangliosidosis with attention to (1) the nature of the associated
      psychiatric and neurologic abnormalities and (2) the treatment of psychosis in
      these patients. RESULTS: The patient's catatonia responded promptly to
      benzodiazepine therapy. Treatment with neuroleptic medication resulted in the
      rapid development of neuroleptic malignant syndrome. The patient was thereafter
      maintained on lorazepam with resolution of his acute psychiatric disturbances and
      unexpected improvement in his neurologic status. CONCLUSION: Patients with
      hexosaminidase deficiency may first present in adolescence or adulthood with
      psychiatric illness, particularly schizophrenic-like psychosis. The presence of
      speech disturbance, gait abnormalities, movement disorders, and cognitive decline
      may indicate an underlying metabolic disorder. The use of traditional
      neuroleptics to treat the psychosis in such individuals may produce an
      unacceptably high risk/benefit ratio. Benzodiazepines may ameliorate the
      psychiatric and neurologic abnormalities in these patients.

PMID- 7635851
TI  - Effect of carbamazepine on agitation in Alzheimer's inpatients refractory to
      neuroleptics.
AB  - BACKGROUND: Agitation in Alzheimer's disease remains a principal problem in the
      clinical management of elderly patients. Neuroleptic medication appears to have
      modest efficacy in controlling behavioral symptoms in dementia patients.
      Carbamazepine has been reported to decrease agitation associated with various
      psychiatric disorders and to reduce neuroleptic side effects. METHOD: In an open
      prospective study, the effects of carbamazepine on agitation, hostility, and
      uncooperativeness were investigated in 15 severely demented Alzheimer's
      inpatients who had failed to respond to prior treatment with neuroleptics.
      Depending on clinical efficacy and tolerability of carbamazepine treatment,
      concomitant medication with haloperidol was initiated. Severity of
      psychopathologic symptoms was assessed by the Brief Psychiatric Rating Scale
      during the study period of 4 weeks. RESULTS: In 2 subjects, carbamazepine
      treatment was discontinued because of leukopenia and allergic reactions. A
      significant improvement in factor scores activation and hostility was observed
      after 4 weeks. Ten patients received concomitant medication with haloperidol.
      CONCLUSION: Carbamazepine may be effective in treating agitation in severely
      demented Alzheimer's inpatients refractory to neuroleptic medication alone. The
      combination of carbamazepine and haloperidol seems to be promising in clinical
      management of elderly Alzheimer's patients.

PMID- 7635852
TI  - EEG abnormalities in patients with atypical panic attacks.
AB  - BACKGROUND: Panic attacks and certain partial seizures have phenomenologic
      similarities which suggest that they may somehow be related. No evidence of such
      a relationship, however, was found when the routine EEGs of patients with panic
      attacks were examined. METHOD: Fifteen subjects with atypical panic attacks who
      met DSM-III-R criteria for panic disorder agreed to have routine followed by
      prolonged ambulatory EEG monitoring with sphenoidal electrodes. Fourteen subjects
      actually underwent monitoring; 1 had a panic attack during premonitoring routine
      EEG. RESULTS: Focal paroxysmal EEG changes consistent with partial seizure
      activity occurred during panic attacks in 33% (N = 5) of the 15 subjects; 2 (40%)
      of the 5 subjects with panic-related EEG changes had normal routine EEGs.
      Multiple attacks were recorded before panic-related EEG changes were demonstrated
      in several subjects. CONCLUSION: It may be necessary to monitor the EEG during
      multiple panic attacks to reveal an association between atypical panic attacks
      and epileptiform EEG changes.

PMID- 7635855
TI  - Sexual function in patients taking bupropion sustained release.

PMID- 7635854
TI  - Predictors of drug treatment response in obsessive-compulsive disorder.
AB  - BACKGROUND: Although a large body of evidence indicates the efficacy of
      pharmacotherapy in the treatment of obsessive-compulsive disorder (OCD), a
      considerable percentage of these patients do not respond. Very few studies focus
      on factors related to treatment response of OCD. The purpose of this study was to
      investigate which clinical factors are related to drug treatment response in OCD.
      METHOD: We examined 53 OCD patients treated with either clomipramine or
      fluoxetine for a period of 6 months, dividing the sample into "responders" and
      "nonresponders" to treatment. At admission, patients were evaluated using a
      semistructured clinical interview, the Yale-Brown Obsessive Compulsive Scale (Y
      BOCS), the Hamilton Rating Scale for Depression, and the Hamilton Rating Scale
      for Anxiety. We then compared acute-phase patient characteristics and response to
      drug treatment. Response was defined as a decrease of at least 40% in the Y-BOCS
      total score and a rating of "improved" or "very improved" on the Clinical Global
      Impressions scale within 16 weeks of treatment and maintained over three
      consecutive evaluations. RESULTS: By the sixth month of treatment, 31 patients
      (58.5%) responded to either clomipramine or fluoxetine. Nonresponders had lower
      age at onset and longer duration of the disorder; in addition, they showed higher
      frequency of compulsions, washing rituals, chronic course, concomitant
      schizotypal personality disorder, and previous hospitalizations. A worse response
      to drug treatment was predicted in a stepwise multiple regression by (1)
      concomitant schizotypal personality disorder, (2) presence of compulsions, and
      (3) longer illness length. CONCLUSION: Our findings suggest that there are
      distinct types of OCD with respect to drug treatment response. They provide
      indirect evidence of treatment specificity by identifying characteristics
      responsive to different modalities, which may be of value in the selection of
      patients for alternative treatments.

PMID- 7635856
TI  - Treatment of organic personality syndrome with low-dose trazodone.

PMID- 7635857
TI  - The high cost of buspirone.

PMID- 7635853
TI  - Major depression and irritable bowel syndrome: is there a relationship?
AB  - BACKGROUND: Irritable bowel syndrome (IBS) has been reported in 10% to 22% of
      adults. Seventy percent to 90% of patients with IBS who seek medical attention
      have psychiatric comorbidity, most commonly major depression. In contrast, few
      studies have looked at the prevalence of IBS among psychiatric patients. METHOD:
      Using a semistructured clinical interview to study the prevalence of IBS, we
      compared 56 patients seeking treatment for major depression in an outpatient
      setting to an age- and sex-matched control group of patients (N = 40) who were
      seeking treatment in a general physician's office for other medical illnesses.
      The control group had no Axis I disorders. IBS was diagnosed according to the
      criteria of Drossman et al. RESULTS: Twenty-seven percent (N = 15) of patients
      with major depression met criteria for IBS in contrast to 2.5% (N = 1) of the
      control group (p = .0005). Patients with major depression and IBS were more
      likely to report symptoms of back pain, weakness, heartburn, and nocturnal bowel
      movements as well as a personal or family history of bowel disease compared with
      patients with major depression but without IBS. CONCLUSION: IBS is fairly common
      in patients seeking treatment for major depression. Prospective studies should
      address the question whether treatment of major depression leads to an
      improvement or resolution of the symptoms of IBS.

PMID- 7635858
TI  - The role for stimulants in the treatment of depressive disorders.

PMID- 7635859
TI  - Carbamazepine-induced hyponatremia resolved with doxycycline.

PMID- 7635860
TI  - Suicide in Gilles de la Tourette's syndrome: report of two cases.

PMID- 7635861
TI  - Social phobia and comorbidity.

PMID- 7635863
TI  - The impact of comorbidity on behavioral and cognitive-behavioral interventions.

PMID- 7635862
TI  - Comorbid social phobia: pharmacologic strategies.

PMID- 7635864
TI  - IMED: the development of a consortium.
AB  - The California Consortium for Informatics in Medical Education and Development
      began in 1990 upon the recommendation of the academic deans of eight California
      medical schools. It provides one model of how consortia can promote the
      development, evaluation, dissemination, and utilization of technology-based
      medical education.

PMID- 7635865
TI  - Compact Disc Interactive (CD-i) multimedia project.
AB  - In 1993, the National Library of Medicine (NLM), in collaboration with the
      National Cancer Institute (NCI), developed a Compact Disc Interactive (CD-i)
      program: "Cervical Cancer: Screening For Life." This was NLM's first experience
      in developing for an all-digital interactive medium, containing motion video,
      graphic images, and text. In 1994, the original CD-i was expanded to include a
      telecommunications capability that allowed the user to obtain the NCI's most
      recent screening and treatment information related to cervical cancer.

PMID- 7635866
TI  - CEA monitoring after primary therapy for colon cancer.

PMID- 7635867
TI  - Inhibitory effect of cold stress on lung tumours induced by 7,12
      dimethylbenz[a]anthracene in mice.
AB  - The effect of cold stress on lung tumours induced by 7,12
      dimethylbenz[a]anthracene (DMBA) was investigated in ICR male and female mice.
      When mice were exposed to cold stress at 0 +/- 1 degree C for 2 h, three times
      per week (every other day) for 3 months, the rectal temperatures and hepatic
      glutathione levels were significantly decreased. On the other hand, when DMBA (10
      mg/kg) was subcutaneously injected into neonatal mice, lung tumours were observed
      in 81.8% of non-stressed mice of both sexes 4 months after injection. However,
      when mice treated with the same dose of DMBA were exposed to cold stress under
      the same conditions, lung tumours were observed in 53.3% and 30.3% of the male
      and female mice 4 months after DMBA injection. In addition, although DMBA (1
      mg/kg) caused lung tumours in 20% or 40% of the treated male or female mice 4
      months after injection, it did not cause lung tumours in all of the male and
      female mice exposed to cold stress. These results suggest that cold stress may
      inhibit lung tumours induced by chemicals.

PMID- 7635868
TI  - Effect of retinoic acid on the structure of N-glycans on the surface of human
      hepatocarcinoma cells and its enzymatic mechanism.
AB  - In order to study the effect of retinoic acid on the structure of N-glycans on
      the cell surface, the N-glycans of glycoproteins on the surface of 7721 human
      hepatocarcinoma cells were labelled with [3H] mannose, added to the culture
      medium. The 3H-labelled N-glycans were prepared from cell-surface glycoproteins,
      desialylated, and subjected to sequential chromatography on concanavalin A and
      Datura stranonium agglutinin affinity columns to separate the glycans into four
      fractions of different type and different antennary number. It was found that the
      percentage of C2C2 biantennary complex type N-glycans was increased, but the high
      mannose type as well as the tri- and tetraantennary complex types, especially
      that with a C2.6 branched structure, were decreased after the cells had been
      treated with retinoic acid for 3-5 days. Using a Lens culinaris agglutinin
      affinity column, it was discovered that the core fucose in the biantennary glycan
      was also decreased. The enzymatic mechanisms of the above changes were revealed
      in further study to involve the decrease of N-acetylglucosaminyl-transferase V
      and core alpha-1,6-fucosyltransferase by retinoic acid.

PMID- 7635870
TI  - Reversal of multidrug resistance by novel cyclosporin A analogues and the
      cyclopeptolide SDZ 214-103 biosynthesized in vitro.
AB  - It was shown that cyclopeptolide SDZ 214-103 (10 microM) is more active in
      rhodamine-123 accumulation in actinomycin-D-resistant human lymphoma cells
      CCRF/ACTD400 than cyclosporin A (10 microM), but equipotent in the doxorubicin
      resistant Friend erythroleukemia cell line F4-6/ADR. In F4-6/ADR cells, the 3
      (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity
      assay showed comparable cytotoxic effects of doxorubicin at various
      concentrations in the presence of SDZ 214-103 and cyclosporin A. For the other
      novel cyclosporin A analogues minor multidrug-resistance-modulating potency was
      demonstrated. At equipotent modulating doses of verapamil (10 microM) and
      cyclosporin A (10 microM) in the MTT assay regarding doxorubicin cytotoxicity,
      cyclosporin A was efficient in the rhodamine-123-uptake assay while verapamil was
      not active when identical incubation times were used.

PMID- 7635869
TI  - Antioxidant enzymes are elevated in dimethylbenz[a]anthracene-induced neoplastic
      murine keratinocytes containing an active rasHa oncogene.
AB  - Antioxidant enzyme activities and peroxidation potential were measured in primary
      mouse keratinocytes and neoplastic keratinocytes containing an active rasHa
      oncogene. In neoplastic cell lines, SP-1 and 308, the activities of Cu, Zn
      superoxide dismutase, catalase, and glutathione transferase were significantly
      elevated. The peroxidation potential was lower in cell homogenates prepared from
      neoplastic keratinocytes than in those prepared from normal keratinocytes.
      Consistently, the neoplastic 308 cell line was found to be more resistant than
      the normal keratinocytes to cytotoxicity induced by UV-B irradiation. The present
      study suggests that the enhanced antioxidant defense system protects the
      initiated cells from UV-B-induced oxidative stress, and that the enhanced enzymic
      antioxidant defense system is potentially a mechanism favoring the selective
      growth of neoplastic keratinocytes.

PMID- 7635871
TI  - Composition and posttranslational modification of individual collagen chains from
      osteosarcomas and osteofibrous dysplasias.
AB  - The composition of collagen was analyzed and the degree of lysyl hydroxylation of
      individual collagen chains was determined in four osteosarcomas and two
      osteofibrous dysplasias. In addition, the tumor proliferation (number of mitoses,
      proliferating-nuclear-antigen-positive cells, MIB) as well as the response to
      chemotherapy (morphological regression grade) were checked. All tumors contained
      a high proportion of collagen III and, in all but one osteosarcoma, pepsin
      extracted collagens I and III were overmodified. Furthermore, the proportion of
      diglycosides in collagen I was about four times higher than in controls. The
      collagen composition and modification resembled those of bones at early stages of
      human development. One osteosarcoma and both osteofibrous dysplasias were in the
      normal range of lysyl hydroxylation. There was no correlation between the
      collagen properties and the histopathological marker of tumor proliferation.

PMID- 7635872
TI  - The usefulness of CA15.3, mucin-like carcinoma-associated antigen and
      carcinoembryonic antigen in determining the clinical course in patients with
      metastatic breast cancer.
AB  - Levels of mucin-like carcinoma-associated antigen (MCA), CA15.3 and
      carcinoembryonic antigen (CEA) were measured in consecutive serum samples of 40
      women with metastatic breast cancer. A change in antigen level of more than 25%,
      either an increase or a decrease, was considered to predict progressive or
      responsive disease respectively. A change of less than 25% was considered to
      predict stable disease. MCA, CA15.3 and CEA were elevated in the serum of 68%,
      76% and 48% of the patients respectively (P < 0.05). The overall prediction of
      clinical course was similar for all three markers. A more than 25% increase of
      MCA, CA15.3, and CEA was observed in 61%, 54% and 36% respectively. The
      predictive value of a more than 25% increase was high for all three markers: 94%,
      94%, 83%. Changes in marker levels were correlated with each other. Logistic
      regression analysis showed that combining MCA and CA15.3 did not improve the
      prediction further. In conclusion, these tumour markers may help in evaluating
      the disease course and there is no advantage in combining MCA and CA15.3.

PMID- 7635876
TI  - 86th annual meeting of the American Association for Cancer Research. Toronto,
      Canada, March 18-22, 1995.

PMID- 7635873
TI  - Growth, microvessel density and tumor cell invasion of human colon adenocarcinoma
      under repeated treatment with hyperthermia and serotonin.
AB  - The intratumoral microvessel density of malignant breast cancer has been shown to
      be an important prognostic marker. In this study, we tested whether repeated
      treatment with hyperthermia and serotonin (5-hydroxytryptamine) reduces tumor
      growth and alters tumor histology of a colon adenocarcinoma, and whether
      capillary density in this tumor can also be regarded as an important prognostic
      marker. Previously we have shown that acute treatment of colon adenocarcinoma
      with hyperthermia, alone or in combination with serotonin, selectively
      constricted tumor microvessels, which could reduce blood flow and inhibit tumor
      growth. Fourteen days after human colon adenocarcinoma had been transplanted
      under the dorsal epidermis of the ear of athymic nude mice, the surgically
      unprepared tumor-bearing ear of the sodium-pentobarbital-anesthetized animal was
      treated with hyperthermia alone (group 1, 43 degrees C for 45 min), or with
      hyperthermia plus topically applied serotonin (1 mM/l, 43 degrees C for 45 min,
      group 2) twice per week for 5 weeks. Control animals were not treated (group 3).
      Histological slides (stained with hematoxylin/eosin) were prepared 42 days after
      implantation, for analysis of tumor grading, tumor cell invasion into the
      surrounding tissue and microvessels, and the number of intratumoral microvessels.
      Repeated hyperthermia inhibited tumor growth, reduced the number of intratumoral
      microvessels, did not change tumor cell invasion and increased the necrotic area.
      Hyperthermia and serotonin did not influence tumor growth, but strongly reduced
      cell invasion and the number of microvessels. The area of necrosis was very
      large. Thus, analysis of microvessel density in colon adenocarcinoma seems not to
      be an important tool for predicting therapeutic efficacy.

PMID- 7635875
TI  - Fourth colloquium on cellular signal transduction. Lipid mediators: signal
      transduction and transport. Heidelberg, Germany, January 1995.

PMID- 7635877
TI  - Benign cartilaginous lesions of the upper extremity.
AB  - Common and rare benign cartilaginous neoplasms and diseases of multiple
      cartilaginous lesions are discussed. Particular attention is paid to patient
      demographics, physical and radiographic findings, pathology, and treatment.

PMID- 7635874
TI  - Expression of retinoblastoma gene (Rb) protein in T12M0 prostatic adenocarcinoma.
AB  - The expression of Rb protein was analysed by immunocytochemical methods in 118
      patients with T12M0 prostatic adenocarcinoma who were followed-up for more than
      12 years. Rb protein was expressed in 117/118 (99%) tumours. The fraction of
      positive nuclei was (mean +/- SD, 92 +/- 19%) and only one tumour was completely
      negative for Rb protein. Abnormal expression of the Rb protein (in fewer than 90%
      of cells) was independent of the T category while there was a significant
      relationship between DNA ploidy (P = 0.0138), S-phase fraction (P = 0.0042) and
      expression of the Rb protein. Abnormal expression of the Rb protein had no
      prognostic value while T category (P = 0.0017), Gleason score (P = 0.0097), DNA
      ploidy (P = 0.0034), S-phase fraction (P = 0.0179) and mitotic index (P = 0.0001)
      were significant prognostic factors. In multivariate analysis the only
      independent predictor was the mitotic index [Risk ratio (RR) (95%CI) = 7.4(2.4
      22.5), P = 0.004]. The results show that Rb protein immunohistochemistry has
      hardly any prognostic significance in prostatic adenocarcinoma whereas direct
      measurement of cell proliferative activity contains significant prognostic
      information.

PMID- 7635878
TI  - Non-neoplastic tumors of the hand and upper extremity.
AB  - A variety of non-neoplastic, tumor-like conditions exist in the upper extremity.
      Some are common, others rare. Careful history, physical diagnosis, and a variety
      of imaging modalities can be helpful in arriving at an accurate diagnosis and
      developing a successful treatment plan for this group of lesions.

PMID- 7635879
TI  - Benign and malignant vascular tumors of the upper extremity.
AB  - Vascular tumors of the upper extremity comprise a wide and varied group of
      pathologies. A variety of benign and malignant tumors exist. Proper diagnosis is
      imperative for the proper management of these lesions. On occasion, diagnosis can
      be made by a careful history and physical examination. However, the
      differentiation of benign from malignant tumors often requires permanent
      histologic section analysis by an experienced tumor specialist. The malignant
      vascular lesions, although rare, are aggressive in their behavior and require
      prompt diagnosis and treatment for patient survival.

PMID- 7635880
TI  - Management considerations for melanonychia striata and melanoma of the hand.
AB  - This article discusses the diagnosis and management of pigmented lesions of the
      hand, especially the nail bed.

PMID- 7635881
TI  - Benign and malignant muscle tumors in the hand and forearm.
AB  - Although soft tissue tumors are common in the hand and forearm, muscle tumors are
      relatively rare. Although presentation may be similar between benign and
      malignant muscle tumors, prognosis can differ tremendously. Accurate and early
      diagnosis is critical to minimize morbidity.

PMID- 7635882
TI  - Benign and malignant nerve tumors.
AB  - Tumors of peripheral nerves in the upper extremity are uncommon. All too
      frequently this diagnosis is made intraoperatively or postoperatively with the
      potential to compromise the outcome of treatment. An appropriate index of
      suspicion is necessary for inclusion of peripheral nerve tumors and a
      differential diagnosis of an upper extremity mass. Knowledge of this group of
      neoplasms will help direct evaluation and treatment.

PMID- 7635884
TI  - Pediatric hand tumors. A review of 349 cases.
AB  - Ganglion cysts, foreign bodies and vascular malformations are some of the most
      common causes of a palpable mass in the pediatric hand. There are other rarer
      tumors, such as digital fibromas, which are unique to the pediatric population.
      Malignant tumors are exceedingly rare. An awareness of both the common and
      unusual tumors seen in the pediatric population is essential for the hand surgeon
      evaluating these patients.

PMID- 7635883
TI  - Osteoid osteoma of the upper extremity.
AB  - Osteoid osteomas, relatively rare lesions in the upper extremity, can be a
      persistent source of hand or wrist pain. Patients under age 40 who have otherwise
      unexplained pain should be evaluated. Relief of pain with oral nonsteroidal anti
      inflammatory drugs should suggest the possibility of osteoid osteoma. Examination
      may demonstrate localized swelling or joint effusion. Radiographs should be
      examined for sclerosis in the region of pain. If radiographs are nondiagnostic, a
      bone scan should be obtained. If the nidus cannot be clearly visualized by
      radiography and bone scan, a CT scan should be obtained. If the location of the
      nidus makes excision difficult without removal of a large block of bone,
      localization with a CT-guided needle or by radioisotope labeling will help to
      assure removal of the nidus.

PMID- 7635885
TI  - Giant cell tumors of tendon sheath.
AB  - Giant cell tumor of tendon sheath represents a common disorder that can present a
      surgical challenge. This article discusses the clinical, histologic, and
      treatment options for this lesion and the technique of excision.

PMID- 7635886
TI  - Nonmelanotic malignant skin tumors of the hand.
AB  - Squamous cell and basal cell carcinomas, the common nonmelanotic skin tumors, are
      the most frequent malignancies to occur in the hand. In spite of a rising
      incidence, these tumors are only occasionally seen by the hand surgeon because of
      their overall rarity. Untreated lesions are locally destructive and may cause
      functional deficits and death by way of metastasis. Appropriate treatment
      consists of timely diagnosis, surgical excision with a margin of normal tissue,
      lymph node dissection for clinically positive nodes or in special circumstances,
      and careful follow-up for recurrence, metastasis or metachronous lesions. The
      aggressive nature of some of the rare nonmelanotic skin tumors that may occur in
      the hand underlines the importance of proper diagnosis of unknown hand tumors.

PMID- 7635887
TI  - Malignant bony tumors of the upper extremity.
AB  - Management of malignant upper-extremity tumors is a complex process that should
      be carried out using all the resources at the disposal of the patient and the
      surgeon. This article focuses on diagnosis, evaluation, pathology, and treatment.

PMID- 7635888
TI  - Soft-tissue sarcomas of the hand and wrist.
AB  - Treatment of soft-tissue sarcomas of the hand cause the ultimate confrontation
      between oncologic outcome and function. The management of hand sarcomas is based
      on knowledge of the specific biology and location of each tumor. This article
      reviews the multimodality management of soft-tissue sarcomas of the hand and
      wrist.

PMID- 7635889
TI  - Vascular tumors in children.
AB  - Tumors with a vascular component are the most common masses seen in children.
      Malformations and hemangiomas predominate. Hemangiomas have a biphasic natural
      history consisting of initial proliferation followed by spontaneous involution;
      these tumors rarely require surgical intervention. Malformations present at birth
      or shortly after birth and have a wide spectrum of clinical presentations
      depending upon their predominant cell type and rheology. Physical examination and
      MR imaging will effectively define most of these anomalies. Surgery is reserved
      for very symptomatic lesions and is effective in all but the fast-flow, Type C
      group of malformations. Glomus tumors, pyogenic granulomas and both traumatic and
      iatrogenic aneurysms are also seen in the pediatric age group. All are benign and
      effectively treated surgically. Malignant vascular tumors are rare in this age
      group.

PMID- 7635890
TI  - Microvascular techniques in limb-sparing surgery.
AB  - Microvascular techniques allowing free tissue transfer have expanded the
      indications for limb salvage in tumor patients. Preoperative planning should
      predict the type of deficit anticipated. Specific techniques for soft tissue,
      skeletal, neurovascular, and composite tissue transfer are discussed. While
      demanding, the use of living autogenous tissue gives the potential for biologic
      adaptivity and life-long durability.

PMID- 7635891
TI  - [Intestinal resection in the treatment of Crohn disease. Retrospective study of a
      series of 106 cases].
AB  - Crohn's disease needs medical and surgical management. Most patients are operated
      and surgical procedure the most often realised is intestinal resection. The
      authors report their experience of 106 intestinal resection performed between
      01/01/1980 and 31/12/1992, in the "service de Chirurgie C" of the "CHU de Nancy"
      for patients operated for the first time for Crohn's disease. They were 54 men
      and 52 women with an average age of 31.7 years at operative time. The following
      clinical patterns were established: small intestine 36, colonic 10 and ileocolic
      60 patients. The average length of evolution before surgery was 4.5 years. The
      main indication was intestinal obstruction in small intestine patterns (91%) and
      poor response to medical therapy in colonic patterns (30%). Usual surgical
      procedure was to remove all visibly diseased bowell with healthy margin of
      resection, as judged by gross examination, of 3 to 5 cm. Postoperative morbidity
      was low (17.9%) with 3 anastomotic leakages. Postoperative morbidity was 1.9% (2
      patients). The average duration of follow-up was 4 years. Among the 106 patients
      operated for the first time for their Crohn's disease, 19 (18%) were operated
      again, at least one time, during the follow-up. The quality of life of operated
      patients is considered as good with only one patient very invalidated by a short
      small bowel syndrome. According to the data of their series and the literature,
      the authors conclude that in Crohn's disease, excisional surgery is able to
      improve patients clinical status account to a low morbidity and mortality, with a
      low risk of short small bowel syndrome as clinical course but it does not avoid
      recurrence.

PMID- 7635892
TI  - [Stomach duplications apropos of a case revealed by digestive hemorrhage. Value
      of ultrasonic endoscopy. Review of the literature].
AB  - Double stomach is a relatively rare inborn malformation. Manifestations are
      usually observed during the neonatal period or in early childhood. In adults,
      complications usually lead to diagnosis. Echographically and endoscopically, the
      malformation takes on the aspect of a tumour of the gastric mesenchyme. Echo
      endoscopy is required for diagnosis. Surgery is the only treatment with or
      without exeresis of the gastric collar surrounding peripheral often pediculated
      lesions. Laparoscopic control may be helpful. Other procedures may be adapted on
      a case by case basis. Prognosis depends on associated malformations.

PMID- 7635893
TI  - [Occlusive pneumatosis cystoides intestinalis of the left colon. Which
      therapeutic approach to choose?].
AB  - A rare case of colonic occlusion due to cystic pneumatosis required surgical
      cure. The problems related to the pathogenesis and, especially, the therapeutic
      approach to this disease were emphasized.

PMID- 7635894
TI  - [Recurrences after conservative radiosurgical treatment of breast cancer].
AB  - From 1960 to 1989, 154 cases of recurrent breast cancer after conservative
      radiosurgery were treated at the Curie Institute. Relapse was discovered at
      clinical examination in 88% of the cases and mammography was only useful in 45%.
      In 18 cases (12%) an unpalpable tumour was discovered at mammography, especially
      for intragalactophoric tumors. Cytopuncture yielded a precise diagnosis in 83% of
      the cases. Overall survival rate after recurrence was 72% at 5 years (62% without
      metastasis). Survival rate was better for late recurrence, and poorer in cases
      with subclinical axillary invasion. Neither age nor type of treatment had any
      effect on survival. Indications for general associated treatment are based on:
      the invasive character of the recurrent tumour, axillary invasion, tumour size
      and delay to recurrence after initial surgery.

PMID- 7635896
TI  - [Distension of the digestive tract. A pathology caused by altitude?].
AB  - A rare manifestation of digestive tract distension involving all the cavities was
      observed in a patient who had journeyed at high altitude. There was no organic
      obstruction suggesting that the increase in organ volume was related to decreased
      atmospheric pressure according to Maiotte's law. Distension may have been
      favoured by the diminished abdominal muscle tone, resulting in a lack of
      adaptation. Dilatation was predominant in the large organs, particularly the
      stomach and the colon.

PMID- 7635895
TI  - [Rupture of an aneurysm of the internal iliac artery into the primary iliac
      vein].
AB  - Authors present a case of spontaneous rupture of internal iliac artery in common
      iliac venous, and propose a review of cases reported in literature. Abreast of
      modern imagery and especially computed tomography is able to give a precise
      diagnosis, but angiography is the Most accurate procedure for detecting
      arteriovenous fistula and cannot be excluded out of diagnostic approach.

PMID- 7635897
TI  - [Subcutaneous cervical emphysema: complication of constipation. Review of the
      literature].
AB  - We report the case of a sixty-eight year old woman with chronic constipation,
      admitted in the emergency unit for respiratory deficiency and cervical
      subcutaneous emphysema. Endoscopy of the supradiaphragmatic air and digestive
      tracts was normal. Acutization of an abdominal syndrome required a laparotomy
      revealing a fissuration of the subperitoneal rectum on a fecal obstruction. This
      revealing complication may be explained by the topography of the cervico-thoraco
      abdominal diffusion spaces.

PMID- 7635898
TI  - [Tuberculosis of the patella. An unusual localization apropos of 2 cases].
AB  - Tuberculosis in an isolated localization in the patella is rarely reported. Five
      cases were found in the literature. Two new cases together with the radiographic
      work-up to be performed in case of a "painful" knee are presented. Histology of
      the curetage specimen is required to reach certain diagnosis and develop an
      adapted management strategy to protect the functional future of the knee.

PMID- 7635899
TI  - [Microcystic adenoma of the pancreas].
AB  - Microcyst adenomas of the pancreas are rare tumours with characteristic cysts
      lining the cubic and cylindric epithelia with a clear cytoplasm rich in glycogen.
      Unlike, mucinous cyst adenomas, there is no tendency toward malignancy. We report
      a case in a 58-year-old woman and emphasize the importance of precise pre- or per
      operative diagnosis in order to avoid excessive exeresis for benign tumour.
      Certain authors propose abstention and follow up.

PMID- 7635900
TI  - [Complications of cholecystectomy by laparoscopy. How can they be avoided?].
AB  - Cholecystectomy was the first digestive tract operation to be performed
      laparoscopically. By far the most frequent laparoscopic operation in France
      (80,000/year) for many surgeons, at least during the first few years after its
      introduction, it was a training operation which generate a higher rate of
      complications than conventional surgery, at least. Today laparoscopic
      cholecystectomy is the accepted reference technique for simple or complicated
      gall stone disease as the incidence of complications is now as low as, or lower
      than open surgery. Excepting puncture accidents (trocars) and pneumoperitonium,
      the most frequent complications are by far related to the biliary tract: wounds,
      stenosis, section. Most of these complications are avoidable with a simple
      rigorous technique. Other complications (haemorrhage, infection) were also
      analyzed to determine the circumstances and means to prevent them.

PMID- 7635901
TI  - [A case of fusiform cell hemangioendothelioma].

PMID- 7635903
TI  - The shrinking postpartum hospital stay.

PMID- 7635902
TI  - [Palmar hyperhidrosis and arteritis of the finger: value of sympathectomy and
      videothoracoscopy].

PMID- 7635904
TI  - Case in point. Pancreatic cancer (confirmed by computed tomography).

PMID- 7635905
TI  - Atrial flutter or atrial fibrillation?

PMID- 7635906
TI  - Fever and chills in an elderly man with a history of blunt trauma.

PMID- 7635907
TI  - Surviving in a managed care environment.

PMID- 7635908
TI  - Does anybody really know how to treat hypertension?

PMID- 7635909
TI  - New-onset ascites in a young man.

PMID- 7635910
TI  - Entrapment neuropathies: clinical overview.
AB  - Causes include congenital defects, trauma, and inflammation. Some forms are
      overdiagnosed, particularly carpal tunnel syndrome. Others--such as thoracic
      outlet syndrome and anterior interosseous nerve syndrome--are rare. Diagnosis and
      management are relatively straightforward in most cases, but much remains to be
      learned about the natural course and prevention of these disorders.

PMID- 7635911
TI  - Glucocorticoid-induced osteoporosis.
AB  - High-dose treatment of more than three months' duration reduces bone mass,
      regardless of the patient's age, sex, or race. Because bone loss is most severe
      during the first six to 12 months of treatment, prophylaxis to preserve bone-
      with calcium, vitamin D, a bisphosphonate, and exercise--should begin as soon as
      the clinical situation permits rather than after the disease has been brought
      under control.

PMID- 7635912
TI  - Ternary complex therapy for autoimmune disease.
AB  - Induction of an immune response is remarkably simple, involving the interaction
      of three components: processed antigen, an MHC class II molecule, and a CD4 T
      cell receptor. Each part of this ternary complex represents a novel target for
      interventions that may block subsequent effector phenomena of autoimmune disease.
      Such specific treatments will be less toxic than those currently available.

PMID- 7635913
TI  - Ring around the cornea in a woman with morning stiffness.

PMID- 7635914
TI  - An approach to antiretroviral treatment of HIV disease. Combined antiretroviral
      therapy: the emerging role.
AB  - Early, aggressive antiretroviral therapy may soon be considered state of the art.
      A new generation of antiretroviral agents will soon be available, many of them
      well tolerated and effective, particularly when used in combination with
      zidovudine and other nucleoside analogues. Combined antiretroviral therapy
      represents a significant step forward in the management of HIV infection.

PMID- 7635915
TI  - An approach to antiretroviral treatment of HIV disease. The situation: an
      overview.

PMID- 7635916
TI  - An approach to antiretroviral treatment of HIV disease. Individualized therapy:
      the role of viral-burden measures.
AB  - Surrogate markers such as the CD4 lymphocyte count and viral p24 antigen level
      have now been joined by assays of HIV nucleic acid in patients' plasma as a
      measure of viral burden. The findings are already assisting in the development
      and clinical testing of antiretroviral agents. They also may facilitate
      therapeutic decision making for the individual patient.

PMID- 7635917
TI  - An approach to antiretroviral treatment of HIV disease. Nucleoside monotherapy.
AB  - Despite hopes for attack of multiple viral targets, the licensed agents now in
      use are all of one type: the nucleoside analogue reverse transcriptase
      inhibitors, of which four, including zidovudine, are available, with a fifth
      likely to follow. Clinicians and patients are still struggling to learn how best
      to employ them; but even now, the available trial results can be distilled into
      rational management plans.

PMID- 7635918
TI  - Optimization of PCR-based diagnostics for human cytomegalovirus.
AB  - Various techniques of DNA template preparation for the PCR-based analysis of
      human CMV in biological fluids have been compared. Structural polymorphism of a
      CMV DNA segment (part of the major immediate early gene) in clinical isolates is
      described; the molecular markers (nucleotide substitutions, deletions,
      insertions) localized in the analyzed amplicon appear to be suitable for
      molecular-epidemiological studies. A scheme of spreading of the molecular markers
      in the population is suggested.

PMID- 7635919
TI  - A two-site enzyme immunoassay for quantitation of human papillomavirus type 16
      particles.
AB  - A group of human papillomaviruses (HPV), in particular HPV type 16, are the major
      cause of anogenital dysplasias, which are precursors of anogenital cancer. The
      mode of transmission, extent of infectivity and natural history of infection are
      incompletely understood because methods to quantify shedding of viral particles
      have not been available. A two-site ELISA was developed to detect and quantify
      HPV-16 particles. Rabbits and guinea pigs were immunized with a series of
      peptides from the L1 and L2 capsid proteins of HPV-16. Among rabbit antipeptide
      sera tested for use as capture antibodies, only sera against one peptide bound
      detectable amounts of virus. Guinea pig antisera against several peptides were
      used as reporter antibodies to detect bound virus particles. If antisera against
      the same peptide were used both as capture antibody and reporter antibody, only
      intact particles were detected. Disrupted particles were quantified using
      antibodies against one L1 peptide as capture antibody and antibodies against
      other L1 peptides as reporter antibody. The lowest detectable amount of virus was
      3 ng (0.06 micrograms/ml). There was no detectable cross-reaction with HPV type 6
      or 11. The assay could be used both with cervical swabs in several common sample
      collection buffers and with surgical material solubilized in NP40-containing
      extraction buffers. Among 15 surgically removed condyloma acuminata, only 1
      specimen was found to contain HPV-16 particles, at a concentration of 375 ng/ml
      (1.1 micrograms/specimen). Among 29 cervical swab samples from patients with
      koilocytotic atypia, 9 samples were found to contain virus. The results indicate
      that this assay is useful for large-scale studies on shedding of HPV particles.

PMID- 7635920
TI  - KCl potentiated inactivation of poliovirus 1 by free chlorine at pH 4.5.
AB  - At 5 degrees C in phthalate buffer at pH 4.5, poliovirus 1 was destroyed 60 to
      70% more rapidly by free chlorine (FC) in the presence of 1,262 mg/L
      (approximately 0.0169 M) KCl than in the absence of KCl. At 5 degrees C, more
      than 99.9% of FC exists as HOCl at pH 4.5. Since buffers themselves may have a
      marked potentiating effect on the virus-inactivating capability of FC, and
      because a maximum ion potentiating effect may occur, the actual degree of
      potentiation of HOCl by KCl may be much greater. Because the level of
      chlorination for drinking water is in large part determined by the rate at which
      the chlorines inactivate viruses in laboratory studies, the potentiation of FC by
      ions normally present in drinking waters may permit reducing chlorination levels
      and with them the levels of carcinogenic and otherwise toxic organic halides
      produced by chlorination.

PMID- 7635923
TI  - A macaque adherent cell line that expresses human CD4 is susceptible to SIV:
      utility for assessing neutralizing antibody.
AB  - A macaque CD4 + adherent cell line was generated by stable expression of the
      human CD4 gene in a rhesus macaque mammary tumor cell line, CMMT. The resulting
      cell line CMMT/CD4 expressed surface CD4 and was sensitive to infection by a wide
      range of isolates of simian immunodeficiency virus (SIV) of different subgroups,
      but was not susceptible to infection with HIV-1. The CMMT/CD4 cell line was used
      to develop a microassay for measurement of neutralizing antibody in plasma of SIV
      infected or immunized animals. Single infected cells could be detected in a
      monolayer of CMMT/CD4 by immunoperoxidase and a 90% reduction in the number of
      positive cells was used as a measure of neutralizing activity of two-fold plasma
      dilutions. This assay had comparable sensitivity to methods based upon detecting
      a reduction in reverse transcriptase activity of SIV, reduction of viral antigen,
      or inhibition of cytopathic effect.

PMID- 7635921
TI  - A single tube nested PCR for the detection of hepatitis C virus RNA.
AB  - An assay was developed for the detection of hepatitis C virus RNA in serum which
      combined cDNA synthesis and a hot start nested polymerase chain reaction (PCR) in
      a single tube. This was made possible by separation of the reagents necessary for
      cDNA synthesis and PCR during cDNA synthesis with a high melting temperature wax
      interface and by the use of 'drop in-drop out' nested primers which enabled each
      primer set to be selectively extended within the same reaction tube. The increase
      in sensitivity following amplification with the internal primer pair was
      comparable to that achieved when nested reactions are carried out separately.

PMID- 7635922
TI  - Quantitative detection of hepatitis B virus DNA in human sera by branched-DNA
      signal amplification.
AB  - Serum samples from 116 patients with hepatitis B surface antigen (HBsAg), from 7
      patients without detectable HBsAg and from 71 healthy blood donors were tested by
      a branched DNA signal amplification (bDNA) method. Hepatitis B virus (HBV) DNA
      was detected in 39 (34%) of the 116 samples with HBsAg, including 19 (70%) of the
      27 patients who were also positive for hepatitis B e antigen (HBeAg). In
      contrast, one of the 7 patients without HBsAg and none of the 71 blood donors
      were positive for HBV DNA. The titers of serum HBV DNA did not correlate with the
      serum alanine aminotransferase levels. All the samples positive by the bDNA assay
      were positive by the polymerase chain reaction (PCR). However, 59% of the PCR
      positive samples were bDNA-negative. None of the PCR-negative samples was
      positive by the bDNA method. Although the sensitivity of bDNA method is not
      entirely satisfactory, it showed excellent specificity and reproducibility. Thus
      it may be considered as an alternative for quantitative detection of HBV DNA in
      serum samples of patients with relatively high titers of HBV viremia.

PMID- 7635924
TI  - Improved method for polyamine determination in TMV, a rod-shaped virus.
AB  - Polyamines were measured in viruses using different techniques. An improved
      method of polyamine analysis is reported for tobacco mosaic virus (TMV), a rod
      shaped virus (95% protein and 5% RNA), based on HPLC of sonicated PCA-treated
      highly purified virus suspensions. This method allowed higher and more reliable
      recovery of TMV polyamines (putrescine, spermidine and spermine) when compared to
      the HPLC of non-sonicated samples and to thin layer chromatography. It is
      suggested that sonication acts on PCA-precipitated protein aggregates causing the
      release of trapped polyamine molecules.

PMID- 7635925
TI  - New method for the extraction of viral RNA and DNA from cerebrospinal fluid for
      use in the polymerase chain reaction assay.
AB  - A new, rapid, and simple method for the isolation of either RNA or DNA from
      cerebrospinal fluid samples for subsequent amplification by specific polymerase
      chain reaction (PCR) assays is described. The technique involves a single
      extraction with a guanidinium thiocyanate acid (GuSCN) buffer, and does not
      require the use of organic solvents. Applied to the recovery of enteroviral RNA,
      herpes simplex virus (HSV) and Varicella-zoster virus (VZV) DNAs the method has
      proved to be of equivalent or better efficiency than established methods of
      nucleic acid separation but is less laborious and time consuming. The simplicity
      of the procedure permits the processing of large numbers of samples and the use
      of a single preparative method for either RNA or DNA PCR makes it an attractive
      method for the routine laboratory.

PMID- 7635927
TI  - Assay of HIV-1 protease activity by use of crude preparations of enzyme and
      biotinylated substrate.
AB  - An enzyme immunoassay was developed for monitoring protease reactions of human
      immunodeficiency virus (HIV). The protease and its substrate, the gag precursor,
      were generated separately in Escherichia coli. The HIV-1 protease was generated
      with a glutathione-S-transferase expression system and the gag substrate, named
      Pin17/24, was prepared with a PinPoint expression system. Pin17/24 consists of an
      N-terminal peptide, which is biotinylated in E. coli, fused with a C-terminal
      peptide that contains a protease cleavage site flanked by p17 and p24 segments.
      Through its biotin in the N-terminal region, Pin17/24 bound to ELISA plates
      coated with avidin, whereas through its C-terminal region, the same molecule of
      Pin17/24 could be recognized by an anti-p24 monoclonal antibody. When the
      protease was added to Pin17/24, the p24 fragment was released from the
      biotinylated fusion protein and could no longer be retained on the avidin plates,
      and as a result, binding of the anti-p24 monoclonal antibody decreased. The
      binding was specific and the reaction was inhibited by a known HIV protease
      inhibitor. Due to the specific interactions between avidin and biotin, monoclonal
      antibody and antigen, and the HIV protease and the gag substrate, crude
      preparations of these reagents can be used readily in the assay. The simplicity
      and feasibility of this method should be useful for simultaneous monitoring of
      many enzyme reactions, particularly for screening possible HIV protease
      inhibitors.

PMID- 7635926
TI  - Differential in situ hybridization for herpes simplex virus typing in routine
      skin biopsies.
AB  - A herpes simplex virus (HSV) type 2 specific recombinant plasmid probe designated
      pH2S3 was constructed from non-HSV-1 crossreactive regions of the HSV-2 genome.
      DNA in situ hybridization on in vitro reconstructed tissue samples of sheep
      collagen matrix impregnated with herpes virus-infected human cells was used to
      demonstrate absence of crossreactivity of the pH2S3 probe with HSV-1 and
      varicella zoster virus under stringent posthybridization washing conditions. It
      was demonstrated that DNA in situ hybridization with pH2S3 allows specific
      detection of HSV-2 in routine formalin-fixed, paraffin-embedded patient material.

PMID- 7635928
TI  - Expression of the major capsid protein of human papillomavirus type 16 in
      Escherichia coli.
AB  - Major capsid proteins (MCPs) of various papillomaviruses have recently been
      expressed in heterologous cells as soluble and functional polypeptides. The host
      cells for producing these proteins have so far been of eukaryotic origin;
      however, E. coli has potential utility a host, with advantages over eukaryotic
      cells such as relatively simple culture requirements and greater ease of mutation
      of expressed sequences. We studied the expression by E. coli of the MCP of human
      papillomavirus type 16 (HPV16) using the gene derived from the 'prototype' HPV16
      genome. Using expression vector pTrc99A, the protein was produced in full-length
      unfused form at levels of 3-4% of cell protein. Soluble polypeptide was detected,
      albeit at low levels. The level of solubility was not increased by growing cells
      at low temperature and slowing the rate of protein synthesis. The soluble protein
      was degraded at its carboxy terminus by an outer membrane protease of E. coli,
      OmpT, giving rise to two slightly shortened protein species of 52K and 56K in
      addition to the full-length 57K polypeptide. Since the MCP of prototype HPV16 is
      known to be prone to excessive aggregation compared with other papillomaviral
      MCPs, the recovery of soluble polypeptide indicates that E. coli is worth
      consideration as an alternative host to eukaryotes for producing these proteins.

PMID- 7635929
TI  - Synthetic oligonucleotide cocktails as probes for detection of human parvovirus
      B19.
AB  - A cocktail of 10 oligonucleotides selected at intervals along the length of the
      genome of human parvovirus B19 was labelled enzymically with digoxigenin and
      chemically with either digoxigenin (DIG) or dinitrophenyl (DNP). Chemical
      labelling was easier and more practical for the production of large quantities of
      probe. Pools labelled with either digoxigenin or DNP could detect 10 fg of B19
      DNA in a dot blot reaction using an alkaline phosphatase antibody conjugate and
      colorimetric detection. Formalin fixed tissue from 11 consecutive cases of fetal
      hydrops were examined by in situ hybridisation (ISH). Both probe cocktails
      detected human parvovirus B19 DNA in 3 cases, with positive cells in all tissues
      examined and with equal sensitivity. The DNP pool is significantly cheaper and
      simpler to produce and could provide an inexpensive reagent suitable for
      diagnostic detection of viral nucleic acid in histopathological material.

PMID- 7635931
TI  - Lack of linkage of apparently dominant cleft lip (palate) to two candidate
      chromosomal regions.
AB  - Two regions were chosen for linkage studies to cleft lip with or without cleft
      palate (CL[P]) because they are break points of a balanced translocation in a
      patient with severe bilateral facial clefting. We used dinucleotide repeats to
      test chromosomal regions 1q21 and 22q11.2 for such linkage. We studied three
      families with apparently dominantly inherited CL(P). Families #1 and #2 are local
      Caucasian families that have not been previously reported; family #3 is a Belgian
      family that has been previously published [DePaepe, 1989]. Significant evidence
      against close linkage of the dinucleotide repeats (D1S104, D22S156, D22S264) with
      CL(P) using a dominant model was obtained. Three other candidate regions were
      tested (2q37,4q31, and 8p) with the dinucleotide repeats PAX3, D4S175, and LPL
      respectively. The LOD scores generated at these three loci are not statistically
      significant for demonstrating negative linkage at these regions. However, they
      may be used with other informative families in the future, since LOD scores for
      the same model of inheritance may be added together. Negative or neutral LOD
      scores were generated at all informative loci using an autosomal dominant model
      with decreased penetrance.

PMID- 7635930
TI  - The CORT-GR signal transduction pathway and CORT-induced cleft palate in H-2
      congenic mice.
AB  - A significant association between genes at or near the H-2 complex and
      glucocorticoid (CORT)-induced cleft palate in mice has been conclusively
      demonstrated. In addition, the frequency of CORT-induced cleft palate in
      heterozygous offspring from reciprocal crosses has been shown to be dependent on
      maternal H-2 haplotype. Although CORT responses are known to be mediated through
      the glucocorticoid receptor (GR), the involvement of H-2 haplotype-specific
      variation in the embryonic CORT-GR signal transduction pathway in CORT
      responsiveness remains uncertain. In this study, we characterized the embryonic
      (E13 to E15) CORT-GR pathway in developing B10 (H-2b) and B10.A (H-2a) mouse
      palates. Northern analysis demonstrates similar GR transcripts and mRNA steady
      state levels in embryonic B10 and B10.A mouse palates. Palatal GR M(r) and pI, as
      determined by Western analysis, are similar between strains and among gestational
      days. We also analyzed possible haplotype-specific qualitative or quantitative
      differences in the ability of the GR to bind a glucocorticoid response element
      (GRE); no significant differences in the GR-GRE complex or in the levels of
      activated GR are seen between strains or among gestational days. Based on these
      results, we conclude that H-2 associated differences in susceptibility to CORT
      induced cleft palate are not associated with either variation in embryonic GR or
      increasing gestational age. To determine if endogenous differences in maternal
      circulating corticosterone levels are related to differential embryonic CORT
      responsiveness, the levels of serum corticosterone were determined by RIA in
      pregnant dams on day 13 of gestation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7635932
TI  - Facial growth and development in unilateral cleft lip and palate from the time of
      palatoplasty to the onset of puberty: a longitudinal study.
AB  - X-ray cephalometry was used for the assessment of facial growth and development
      from the time of palate surgery to the onset of puberty (from 5 to 11 years) in
      24 boys with unilateral cleft lip and palate treated with primary periosteoplasty
      (at 8 months) and palatal pushback supplemented by pharyngeal flap surgery (at 5
      years). The lowest growth showed the depth of the maxilla and the height of the
      upper lip. An increasing protrusion of the mandible and in particular the
      increasing retrusion of the maxilla resulted in a flattening of the face and in
      an impairment of sagittal jaw relations. However, it was possible to attain an
      improvement of overjet produced by a substantial increase of the proclination of
      upper incisors and of the alveolar process. There was a deterioration of the
      prominence of the upper lip. Anterior growth rotation was absent during the
      development of the face, though a rotation in both directions was quite common in
      individual cases. The steepness of the mandibular body, vertical jaw relations,
      and facial vertical proportions remained unchanged. As compared to the pubertal
      period, the growth and development differed only by a more marked proclination of
      the dentoalveolar component of the maxilla and by an improvement of overjet.
      Facial convexity and sagittal jaw relations deteriorated in more than 90% of the
      patients, the overjet only in 20%, yet the prominence of the lip in 70%. Facial
      convexity and sagittal jaw relations were not correlated with mandibular rotation
      but they affected the overjet and the prominence of the upper lip.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7635933
TI  - Normal prenatal development of the human parietal bone and interparietal suture.
AB  - This study describes the prenatal human parietal bone development and
      interparietal suture morphology under normal conditions. The human fetal material
      consisted of 15 normal specimens, derived from spontaneous and therapeutically
      induced abortions. The study was based upon a radiographic analysis of the
      calvariae. Special attention was paid to the parietal tuber area, the
      interparietal (sagittal) suture and the frontal-parietal bone edge. The osseous
      morphology of these regions showed a well-defined primary ossification center at
      the tuber region from where bone trabeculae of uniform size and radiopacity
      radiated. The uniform trabeculae radiate at nearly right angles to the long axis
      of the sagittal suture. The bony trabeculae radiate uniformly towards the
      anterior fontanelle where at the peripheral border of the parietal bone
      radiopaque, transverse ossification corpora were observed. In the small fetuses,
      these corpora were located anterior to the trabeculae and in the larger fetuses
      close to the trabeculae. Insight into the morphological pattern in normal suture
      formation is essential for the further description of pathological suture
      morphology and for understanding normal and pathological suture development.

PMID- 7635934
TI  - Kallmann syndrome and delayed puberty associated with agenesis of lateral
      maxillary incisors.
AB  - In six adolescents, we documented the association of either Kallmann syndrome or
      delayed puberty with agenesis of the lateral maxillary incisors. As the neurons
      secreting gonadotropin-releasing hormone originate from the olfactory placode,
      this newly recognized association appears to be the clinical expression of a
      developmental field defect.

PMID- 7635935
TI  - Diprosopia revisited in light of the recognized role of neural crest cells in
      facial development.
AB  - OBJECTIVE: The aim of this study is to compare the theory of embryogenesis of the
      face with human diprosopia. This peculiar form of conjoined twinning is of great
      interest because 1) only the facial structures are duplicated and 2) almost all
      cases have a rather monomorphic pattern. The hypothesis is that an initial
      duplication of the notochord leads to two neural plates and subsequently
      duplicated neural crests. In those conditions, derivatives of the neural crests
      will be partially or totally duplicated; therefore, in diprosopia, the duplicated
      facial structures would be considered to be neural crest derivatives. If these
      structures are identical to those that are experimentally demonstrated to be
      neural crest derivatives in animals, these findings are an argument to apply this
      theory of facial embryogenesis in man. METHODS: Serial horizontal sections of the
      face of two diprosopic fetuses (11 and 21 weeks gestation) were studied macro-
      and microscopically to determine the external and internal structures that are
      duplicated. Complete postmortem examination was performed in search for
      additional malformations. RESULTS: The face of both fetuses showed a very similar
      morphologic pattern with duplication of ocular, nasal, and buccal structures. The
      nasal fossae and the anterior part of the tongue were also duplicated, albeit the
      posterior part and the pharyngolaryngeal structures were unique. Additional
      facial clefts were present in both fetuses. Extrafacial anomalies were
      represented by a craniorachischisis, two fused vertebral columns and, in the
      older fetus, by a complex cardiac malformation morphologically identical to
      malformations induced by removal or grafting of additional cardiac neural crest
      cells in animals. CONCLUSION: These pathological findings could identify the
      facial structures that are neural crest derivatives in man. They are similar to
      those experimentally demonstrated to be neural crest derivatives in animals. In
      this respect, diprosopia could be considered as the end of a spectrum, whereas
      the other end is agnathia-holoprosencephaly complex. This assumption has to be
      discussed, but we want to draw attention to the fact that diprosopia must not be
      considered as a curious form of conjoined twinning, but as a major means of
      bringing us a better knowledge of the facial embryogenesis in man.

PMID- 7635936
TI  - Insulin action on heart and skeletal muscle glucose uptake in essential
      hypertension.
AB  - Essential hypertension is characterized by skeletal muscle insulin resistance but
      it is unknown whether insulin resistance also affects heart glucose uptake. We
      quantitated whole body (euglycemic insulin clamp) and heart and skeletal muscle
      (positron emission tomography and 18F-fluoro-2-deoxy-D-glucose) glucose uptake
      rates in 10 mild essential hypertensive (age 33 +/- 1 yr, body mass index 23.7 +/
      0.8 kg/m2, blood pressure 146 +/- 3/97 +/- 3 mmHg, VO2max 37 +/- 3 ml/kg per
      min) and 14 normal subjects (29 +/- 2 yr, 22.5 +/- 0.5 kg/m2, 118 +/- 4/69 +/- 3
      mmHg, 43 +/- 2 ml/kg per min). Left ventricular mass was similar in the
      hypertensive (155 +/- 15 g) and the normotensive (164 +/- 13 g) subjects. In the
      hypertensives, both whole body (28 +/- 3 vs 44 +/- 3 mumol/kg per min, P < 0.01)
      and femoral (64 +/- 11 vs 94 +/- 8 mumol/kg muscle per min, P < 0.05) glucose
      uptake rates were decreased compared to the controls. In contrast, heart glucose
      uptake was 33% increased in the hypertensives (939 +/- 51 vs 707 +/- 46 mumol/kg
      muscle per min, P < 0.005), and correlated with systolic blood pressure (r =
      0.66, P < 0.001) and the minute work index (r = 0.48, P < 0.05). We conclude that
      insulin-stimulated glucose uptake is decreased in skeletal muscle but increased
      in proportion to cardiac work in essential hypertension. The increase in heart
      glucose uptake in mild essential hypertensives with a normal left ventricular
      mass may reflect increased oxygen consumption and represent an early signal which
      precedes the development of left ventricular hypertrophy.

PMID- 7635937
TI  - Murine laminin binds to Histoplasma capsulatum. A possible mechanism of
      dissemination.
AB  - Histoplasmosis, an increasingly important opportunistic infection in
      immunosuppressed subjects, is characterized by hematogenous dissemination of the
      yeast from the lung. The mechanism of this dissemination is not fully understood.
      Laminin, the major glycoprotein of the extracellular matrix, is known to mediate
      the attachment of various invasive pathogens to host tissues. In the current
      study, laminin is demonstrated to bind to Histoplasma capsulatum in a rapid,
      specific, and saturable manner. Scatchard analysis with 125I-labeled laminin
      revealed an estimated 3.0 x 10(4) binding sites per yeast with an apparent Kd for
      laminin binding of 1.6 x 10(-9) M. Laminin binding to H. capsulatum was decreased
      from 62 +/- 1 to 17 +/- 1 ng (P < 0.001) in the presence of 3,000 nM of Ile-Lys
      Val-Ala-Val, a pentapeptide within one major cell attachment site of laminin. A
      50-kD H. capsulatum laminin-binding protein was demonstrated using an 125I-Ln
      blot of H. capsulatum cell wall proteins. The 50-kD protein is also recognized by
      antibodies directed at the 67-kD laminin receptor, suggesting they are related.
      This study proposes a possible mechanism for H. capsulatum attachment to laminin,
      an important first step required for the yeast to recognize and traverse the
      basement membrane.

PMID- 7635938
TI  - Induction of heparin-binding epidermal growth factor-like growth factor mRNA in
      rat kidney after acute injury.
AB  - Previous studies have suggested that EGF or other members of the EGF family of
      mitogenic proteins are involved in proliferation of renal tubular epithelial
      cells occurring during recovery from injury to the kidney. The present studies
      examined whether expression of mRNA for the recently identified heparin-binding
      EGF-like growth factor (HB-EGF) is regulated in response to renal injury induced
      by either ischemia/reperfusion or mercuric chloride. Increased expression of HB
      EGF mRNA was demonstrated in the post-ischemic kidney within 45 min of unilateral
      ischemia/reperfusion in the rat. Induction of HB-EGF mRNA occurred only when
      ischemia was followed by reperfusion, and was not eliminated by removal of blood
      cells from the post-ischemic kidney by saline perfusion. In situ hybridization
      with 35S-labeled antisense riboprobes of HB-EGF indicated that compared with
      control, there was increased HB-EGF mRNA expression in the 6 h post-ischemic
      kidney in the inner cortex and outer medulla in a patchy distribution, with the
      greatest expression in the inner stripe of the outer medulla. Expression occurred
      primarily in tubular epithelial cells. Recombinant human HB-EGF stimulated [3H]
      thymidine incorporation in both primary cultures of rabbit proximal tubule cells
      and NRK 52E normal rat kidney epithelial cells, with potency similar to that of
      EGF. Induction of HB-EGF mRNA was observed in tubules freshly isolated from rat
      renal cortex or outer medulla when the tubules were subjected to reoxygenation
      after incubation in anoxic conditions. The nephrotoxin, mercuric chloride, also
      caused induction of HB-EGF mRNA both in vivo and in isolated rat cortical
      tubules. The anoxia/reoxygenation-induced expression of HB-EGF mRNA in isolated
      tubules was inhibited by the free radical scavengers, di- and tetra
      methylthiourea, indicating involvement of reactive oxygen species. These findings
      indicate that HB-EGF mRNA is inducible in the kidney in vivo by acute tubular
      injury and suggest that HB-EGF may act as an autocrine/paracrine growth factor
      involved in proliferation of tubular epithelial cells and repair of the kidney.

PMID- 7635940
TI  - Tumor necrosis factor-alpha gene and protein expression in adult feline
      myocardium after endotoxin administration.
AB  - TNF alpha mRNA and protein biosynthesis were examined in the adult feline heart
      after stimulation with endotoxin. When freshly isolated hearts were stimulated
      with endotoxin in vitro, de novo TNF alpha mRNA expression occurred within 30
      min, and TNF alpha protein production was detected within 60-75 min; however, TNF
      alpha mRNA and protein production were not detected in diluent-treated hearts.
      Immunohistochemical studies localized TNF alpha to endothelial cells, smooth
      muscle cells, and cardiac myocytes in the endotoxin-treated hearts, whereas TNF
      alpha immunostaining was absent in the diluent-treated hearts. To determine
      whether the cardiac myocyte was a source for TNF alpha production, two studies
      were performed. First, in situ hybridization studies, using highly specific
      biotinylated probes, demonstrated TNF alpha mRNA in cardiac myocytes from
      endotoxin-stimulated hearts; in contrast, TNF alpha mRNA was not expressed in
      myocytes from diluent-treated hearts. Second, TNF alpha protein production was
      observed when cultured cardiac myocytes were stimulated with endotoxin, whereas
      TNF alpha protein production was not detected in the diluent-treated cells. The
      functional significance of the intramyocardial production of TNF alpha was
      determined by examining cell motion in isolated cardiac myocytes treated with
      superfusates from endotoxin- and diluent-stimulated hearts. These studies showed
      that cell motion was depressed in myocytes treated with superfusates from the
      endotoxin-treated hearts, but was normal with the superfusates from the diluent
      treated hearts; moreover, the negative inotropic effects of the superfusates from
      the endotoxin-treated hearts could be abrogated completely by pretreatment with
      an anti-TNF alpha antibody. Finally, endotoxin stimulation was also shown to
      result in the intramyocardial production of TNF alpha mRNA and protein in vivo.
      Thus, this study shows for the first time that the adult mammalian myocardium
      synthesizes biologically active TNF alpha.

PMID- 7635941
TI  - The role of fibrinogen D domain intermolecular association sites in the
      polymerization of fibrin and fibrinogen Tokyo II (gamma 275 Arg-->Cys).
AB  - Intermolecular end-to-middle domain pairing between a thrombin-exposed 'A'
      polymerization site in the central 'E' domain of fibrin, and a constitutive
      complementary 'a' site in each outer 'D' domain ('D:E'), is necessary but not
      alone sufficient for normal fibrin assembly, as judged from previous studies of a
      congenital dysfibrinogen, Tokyo II (gamma 275 arg-->cys), which showed defective
      fibrin clot assembly and a normal D:E interaction (Matsuda, M., M. Baba, K.
      Morimoto, and C. Nakamikawa, 1983. J. Clin. Invest. 72:1034-1041). In addition to
      the 'a' polymerization site, two other constitutive intermolecular association
      sites on fibrinogen D domains have been defined: between gamma chain regions
      containing the carboxy-terminal factor XIIIa crosslinking site ('gamma XL:gamma
      XL'); and between sites located at the outer ends of each molecule ('D:D')
      (Mosesson, M. W., K. R. Siebenlist, J. F. Hainfeld, and J. S. Wall, manuscript
      submitted for publication). We evaluated the function of these sites in Tokyo II
      fibrinogen, and confirmed that there was a normal fibrin D:E interaction, as
      determined from a normal fibrin crosslinking rate in the presence of factor
      XIIIa. We also found a normal gamma XL: gamma XL interaction, as assessed by a
      normal fibrinogen crosslinking rate. Judging from electron microscopic images,
      factor XIIIa-crosslinked Tokyo II fibrinogen failed to form elongated double
      stranded fibrils like normal fibrinogen. Instead, it formed aggregated disordered
      collections of molecules, with occasional short fibrillar segments. In addition,
      Tokyo II fibrin formed an abnormal, extensively branched clot network containing
      many tapered terminating fibers. These findings indicate that the Tokyo II
      fibrinogen defect results in a functionally abnormal D:D self-association site,
      and that a normal D:D site interaction is required, in addition to D:E, for
      normal fibrin or fibrinogen assembly.

PMID- 7635939
TI  - Restricted usage of T cell receptor V alpha-V beta genes in infiltrating cells in
      the hearts of patients with acute myocarditis and dilated cardiomyopathy.
AB  - Prolonged myocardial cell damage initiated by acute myocarditis is thought to be
      one of the most important etiology of dilated cardiomyopathy. To investigate the
      immunological mechanisms involved in the pathogenesis of dilated cardiomyopathy,
      we analyzed the phenotypes of infiltrating cells and examined the expression of
      perforin in infiltrating cells in the hearts of patients with dilated
      cardiomyopathy as well as acute myocarditis. We also examined the expression of
      HLA and intercellular adhesion molecule-1 (ICAM-1) in myocardial tissue of these
      patients. Furthermore, to evaluate the antigen specificity of infiltrating T
      cells and persistence of viral genomes in the myocardial tissue, we analyzed the
      expression of T cell receptor (TCR) V alpha and V beta genes as well as
      enterovirus genomes by PCR. We found infiltration of perforin-expressing killer
      cells and enhanced expression of HLA class I and ICAM-1 in the myocardial tissue.
      We also found that the repertoires of TCR V alpha as well as V beta gene
      transcripts were restricted, indicating that a specific antigen in the hearts was
      targeted. Because no enterovirus genomes were detected in all patients, it is
      strongly suggested that a cell-mediated autoimmune mechanism triggered by virus
      infection may play a critical role in the pathogenesis of dilated cardiomyopathy.
      However, we could not exclude the possibility that viruses other than
      enteroviruses could be pathogenic in these patients.

PMID- 7635942
TI  - Natriuretic peptides inhibit angiotensin II-induced proliferation of rat cardiac
      fibroblasts by blocking endothelin-1 gene expression.
AB  - The present study was aimed to test the role of endothelin-1 (ET-1) as a possible
      autocrine/paracrine growth factor for cardiac fibroblasts, and to examine its
      interaction with cardiac natriuretic hormones. Expression of preproET-1 (ppET-1)
      mRNA by cultured cardiac fibroblasts from neonatal rats was demonstrated by
      Northern blot analysis using cDNA for rat ppET-1 as a probe. Angiotensin II (ANG
      II) and ET-1 transiently (30 min) increased steady-state ppET-1 mRNA levels in
      cardiac fibroblasts. Both ET-1 and ANG II significantly stimulated [3H] thymidine
      incorporation into cardiac fibroblasts, whose effects were dose-dependently
      inhibited by an ETA receptor antagonist (BQ123), BQ123 also inhibited both ET-1-
      and ANG II-induced ppET-1 mRNA expression. Both atrial and brain natriuretic
      peptides (ANP, BNP), which activate particulate guanylate cyclase, inhibited ppET
      1 mRNA expression and [3H]thymidine incorporation stimulated by ANG II and ET-1.
      Sodium nitroprusside, a soluble guanylate cyclase activator, and 8-bromocyclic
      GMP, a membrane-permeable cGMP derivative, similarly inhibited ppET-1 mRNA
      expression and [3H]-thymidine incorporation. BNP was more potent than ANP to
      inhibit ANG II- and ET-1-stimulated DNA synthesis, whereas BNP and ANP were
      almost equipotent in stimulating cGMP generation in cardiac fibroblasts. Our data
      demonstrated that ANG II and ET-1 upregulate ET-1 gene expression in rat cardiac
      fibroblasts partly via cyclic GMP-dependent mechanism, and that natriuretic
      peptides inhibit ANG II-stimulated proliferation of cardiac fibroblasts, possibly
      by inhibiting ET-1 gene expression. Our data suggest the possible role of
      endogenous ET-1 as an autocrine/paracrine growth factor for cardiac fibroblasts
      and its close interaction with natriuretic peptides in the regulation of cardiac
      fibrosis.

PMID- 7635944
TI  - Interleukin-1 beta modulates the growth and phenotype of neonatal rat cardiac
      myocytes.
AB  - Mononuclear cell infiltration and local cytokine elaboration are hallmarks of
      inflammatory and immunologic heart diseases. To test the hypothesis that
      cytokines can modulate cardiac myocyte growth and phenotype, myocytes cultured
      from neonatal rat hearts were exposed to IL-1 beta, an inflammatory cytokine
      prevalent in myocardial inflammation. IL-1 beta (2 ng/ml, 24 h) increased
      [3H]leucine incorporation by 30 +/- 4% (P < 0.001, n = 29) and net cellular
      protein content by 20 +/- 4% (P < 0.001, n = 27), but had no effect on DNA
      synthesis. Northern hybridization showed that IL-1 beta increased prepro-atrial
      natriuretic factor (ANF) mRNA (5.8 +/- 1.5-fold, P < 0.01, n = 13) and beta
      myosin heavy chain (beta-MHC) mRNA (> 10-fold, n = 4), and decreased mRNA levels
      for sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2) (-46 +/- 7%; P < 0.001; n =
      11), calcium release channel (CRC) (-65 +/- 11%, P < 0.001, n = 8) and voltage
      dependent calcium channel (VDCC) (-53 +/- 7%, P < 0.001, n = 8). NG-monomethyl-L
      arginine (1 mM), an inhibitor of nitric oxide (NO) synthesis, did not inhibit the
      IL-1 beta-induced protein synthesis or changes in mRNA levels. In ventricular
      myocardium obtained from adult rats treated with lipopolysaccharide (4 mg/kg
      intraperitoneally 18 h) to stimulate systemic cytokine production, there were
      changes in the mRNA levels for beta-MHC (6 +/- 1-fold, P < 0.01, n = 4), SERCA2 (
      65 +/- 4%, P < 0.0001, n = 4), CRC (-67 +/- 5%, P < 0.001, n = 4), and VDCC (-58
      +/- 5%, P < 0.001; n = 4) that were qualitatively similar to those observed in
      cultured myocytes. Thus, IL-1 beta, acting via an NO-independent mechanism,
      caused myocyte hypertrophy associated with induction of fetal genes (ANF and beta
      MHC) and downregulation of three important calcium regulatory genes (SERCA2, CRC,
      and VDCC). IL-1 beta may contribute to the abnormal structural and functional
      alterations of cardiac myocytes in conditions marked by mononuclear cell
      infiltration.

PMID- 7635943
TI  - Recurrent ischemia in the canine heart causes recurrent bursts of free radical
      production that have a cumulative effect on contractile function. A
      pathophysiological basis for chronic myocardial "stunning".
AB  - Open-chest dogs (total number used, 117) underwent 10 5-min coronary occlusions
      (O) interspersed with 10 min of reperfusion (R). When systolic thickening
      fraction was measured 9 min after each R, the first O-R cycle was found to cause
      the largest decrement, with only a slight additional loss during the next four
      cycles and no further loss during the last five cycles (group IV), suggesting
      that the first few episodes of ischemia preconditioned the myocardium against the
      stunning induced by the last five episodes. However, different results were
      obtained when the total deficit of wall thickening during the final 4-h R
      interval was measured. The total deficit was similar after one and three 5-min O
      (groups V and VI, respectively), indicating that the first ischemic episode did
      precondition against the next two episodes; however, it was approximately 2.5
      fold greater after 10 O (group IV) than after 3, indicating that the first 3
      episodes failed to precondition against the next 7. Thus, at some point between
      the 4th and 10th O, the preconditioning effect was lost and recurrent ischemic
      episodes started to have a cumulative effect. Measurements of free radicals with
      alpha-phenyl N-tert-butyl nitrone (PBN) demonstrated a burst of free radical
      generation immediately after the 1st, 5th, and 10th R (group VIII). The total
      cumulative release of PBN adducts during the initial 5 min of reflow was 58% less
      after the 5th R than after the 1st (P < 0.05) but did not differ significantly
      between the 1st and 10th R. When administered throughout the 10 O-R cycles, the
      .OH scavenger mercaptopropionyl glycine significantly enhanced the recovery of
      function (group I) and markedly suppressed the formation of free radicals (group
      VII). However, the beneficial effects of mercaptopropionyl glycine were
      completely, or largely, lost if the drug was discontinued after the first five
      (group II) or eight (group III) O-R cycles, respectively, implying that (a) the
      oxidative stress associated with the last five, or even two, cycles was
      sufficient to cause severe postischemic dysfunction, and (b) the cumulative
      injury caused by repetitive ischemic episodes is mediated by recurrent oxidative
      stress. This study provides direct in vivo evidence that oxygen radicals play an
      important role in the pathogenesis of myocardial stunning after repetitive
      ischemia, and implicates .OH as a primary culprit. Taken together, the data
      indicate that recurrent brief ischemic episodes result in recurrent bouts of
      oxyradical-mediated injury that have a cumulative effect on contractility, a
      situation that could lead to protracted or even chronic myocardial stunning.

PMID- 7635945
TI  - Dominant expression of type III hyperlipoproteinemia. Pathophysiological insights
      derived from the structural and kinetic characteristics of ApoE-1 (Lys146-->Glu).
AB  - Type III hyperlipoproteinemia is characterized by delayed chylomicron and VLDL
      remnant catabolism and is associated with homozygosity for the apoE-2 allele. We
      have identified a kindred in which heterozygosity for an apoE mutant, apoE-1
      (Lys146-->Glu), is dominantly associated with the expression of type III
      hyperlipoproteinemia. DNA sequence analysis of the mutant apoE gene revealed a
      single-point mutation that resulted in the substitution of glutamic acid (GAG)
      for lysine (AAG) at residue 146 in the proposed receptor-binding domain of apoE.
      The pathophysiological effect of this mutation was investigated in vivo by
      kinetic studies in the patient and six normal subjects, and in vitro by binding
      studies of apoE-1 (Lys146-->Glu) to LDL receptors on human fibroblasts and to
      heparin. The kinetic studies revealed that apoE-1 (Lys146-->Glu) was catabolized
      significantly slower than apoE-3 in normals (P < 0.005). In the proband, the
      plasma residence times of both apoEs were substantially longer and the production
      rate of total apoE was about two times higher than in the control subjects. ApoE
      1 (Lys146-->Glu) was defective in interacting with LDL receptors, and its ability
      to displace LDL in an in vitro assay was reduced to 7.7% compared with apoE-3.
      The affinity of apoE-1 (Lys146-->Glu) to heparin was also markedly reduced
      compared with both apoE-2 (Arg158-->Cys) and apoE-3. These abnormal in vitro
      binding characteristics and the altered in vivo metabolism of apoE-1 (Lys146-
      >Glu) are proposed to result in the functional dominance of this mutation in the
      affected kindred.

PMID- 7635947
TI  - Treatment of severe hypercholesterolemia in apolipoprotein E-deficient mice by
      bone marrow transplantation.
AB  - Apo E, a key regulator of cholesterol-rich lipoprotein metabolism, is synthesized
      by numerous extrahepatic tissues. Although its synthesis in macrophages is
      documented, the contribution of macrophage-derived apo E to hepatic clearance of
      serum cholesterol is unknown. To address this issue bone marrow transplantation
      was performed on hypercholesterolemic apo E-deficient mice with either syngeneic
      apo E-deficient mouse bone marrow cells (E0-control) or wild-type mouse bone
      marrow cells expressing apo E (E0-treated). E0-control and E0-treated mice were
      fed either a regular chow diet or an atherogenic diet (designated E0-control-HF
      and E0-treated-HF). Serum cholesterol levels dropped dramatically in the E0
      treated mice largely due to a reduction in their VLDL cholesterol. No changes
      were seen in the E0-control mice. After 4 wk serum cholesterol in E0-treated-HF
      mice was about four-fold lower compared to E0-control-HF animals. Moreover, the
      extent of atherosclerosis in the E0-treated-HF mice after 14-16 wk was greatly
      reduced. Wild-type apo E mRNA was detected in the liver, spleen, and brain of the
      E0-treated mice indicating that apo E gene transfer was successfully achieved
      through bone marrow transplantation. More importantly, the level of apo E
      expression was sufficient to reduce the severe hypercholesterolemia of the apo E
      deficient mice fed either chow or atherogenic diets.

PMID- 7635946
TI  - The delta T cell receptor repertoire in human colon and peripheral blood is
      oligoclonal irrespective of V region usage.
AB  - The majority of gamma/delta T cell receptors (TCR) in the human intestinal mucosa
      are thought to use the TCRDV1 (V delta 1) variable region gene segment, whereas
      gamma/delta T cells in the circulation predominantly express the TCRDV2 (V delta
      2) gene segment. delta T cell receptors that use the TCRDV2 variable region gene
      segment generally have been regarded as highly diverse, whereas those that use
      the TCRDV1 gene segment are oligoclonal, whether present in the intestinal tract
      or in peripheral blood. We report herein that oligoclonality is a general feature
      of the peripheral delta T cell receptor repertoire in healthy human adults,
      irrespective of the variable region used and regardless of whether gamma/delta T
      cells reside in the intestinal mucosa or in peripheral blood. In addition, the
      delta T cell receptor repertoire is shown to be highly compartmentalized between
      such sites as the colon and peripheral blood, relatively stable over at least a
      10-16-mo period, and unique in each individual. Further, the spectrum of variable
      region genes used by delta T cell receptor transcripts in the human colon is
      greater than previously recognized. Thus, in addition to the TCRDV1 and TCRDV2
      variable region gene segments, delta T cell receptors in normal intestinal mucosa
      can use TCRDV3 (V delta 3) and TCRAV (V alpha) gene segments which, in some
      individuals, comprise a significant component of the mucosal delta T cell
      receptor repertoire. Our studies indicate that the potential of delta T cell
      receptors for extensive diversity is not reflected in the mature human
      repertoire. Moreover, these findings suggest a model wherein the delta T cell
      receptor repertoire in the colon and peripheral blood is shaped by selection and
      clonal expansion of gamma/delta T cells that ultimately seed throughout the
      length of the colon mucosa and populate the circulation.

PMID- 7635948
TI  - Effective prevention of thrombocytopenia in mice using adenovirus-mediated
      transfer of HST-1 (FGF-4) gene.
AB  - HST-1 (FGF-4) gene product is a member of the fibroblast growth factor family
      with a signal peptide and plays a crucial role in limb development. We showed
      previously that an intraperitoneal injection of replication-deficient adenovirus
      containing the HST-1 gene (Adex1HST-1) into normal mice caused a twofold increase
      in peripheral platelet count. To investigate whether Adex1HST-1 could effectively
      prevent experimentally induced thrombocytopenia in mice, we injected Adex1HST-1
      intraperitoneally into thrombocytopenic mice induced by administration of a
      chemotherapeutic agent and/or by irradiation. A single Adex1HST-1 injection
      caused continuously increased levels of serum HST-1 protein for at least 30 d and
      increased the count of large megakaryocytes in bone marrow, which specifically
      recovered platelet counts and more efficiently diminished the extent and duration
      of thrombocytopenia than any other reported cytokine or any combination of
      cytokines so far. In the other peripheral hematological parameters, no
      discernible differences were detected. No other apparent side effects were
      observed. Therefore, this method could be useful for treatment and/or prevention
      of thrombocytopenia induced by chemotherapy and/or irradiation for cancer
      treatment.

PMID- 7635949
TI  - Mitochondrial respiration scavenges extramitochondrial superoxide anion via a
      nonenzymatic mechanism.
AB  - We determined that mitochondrial respiration reduced cytosolic oxidant stress in
      vivo and scavenged extramitochondrial superoxide anion (O2-.) in vitro. First,
      Saccharomyces cerevisiae deficient in both the cytosolic antioxidant cupro-zinc
      superoxide dismutase (Cu,Zn-SOD) and electron transport (Rho0 state) grew poorly
      (P < 0.05) in 21% O2 compared with parent yeast and yeast deficient only in
      electron transport or Cu,Zn-SOD, whereas anaerobic growth was the same (P > 0.05)
      in all yeast. Second, isolated yeast and mammalian mitochondria scavenged
      extramitochondrial O2-. generated by xanthine/xanthine oxidase. Yeast
      mitochondria scavenged 42% more (P < 0.05) extramitochondrial O2-. during
      pyruvate/malate-induced respiration than in the resting state. Addition of either
      antimycin (respiratory chain inhibitor) or FCCP (respiratory chain uncoupler)
      prevented increased O2-. scavenging. Mitochondria isolated from yeast deficient
      in the mitochondrial manganous superoxide dismutase (Mn-SOD) increased (P < 0.05)
      O2-. scavenging 56% during respiration. This apparent SOD activity, expressed in
      units of SOD activity per milligram of mitochondrial protein, was the same (9 +/-
      0.6 vs. 10 +/- 1.0; P = 0.43) as the O2-. scavenging of mitochondria with Mn-SOD,
      suggesting that respiration-dependent mitochondrial O2-. scavenging was
      nonenzymatic. Finally, isolated rat liver and lung mitochondria also increased (P
      < 0.05) O2-. scavenging during respiration. We speculate that respiring
      mitochondria, via the protonmotive pump, present a polarized, proton-rich surface
      that enhances nonenzymatic dismutation of extramitochondrial O2-. and that this
      is a previously unrecognized function of mitochondrial respiration with potential
      physiological ramifications.

PMID- 7635950
TI  - Expression of transforming growth factor-beta 1 in dystrophic patient muscles
      correlates with fibrosis. Pathogenetic role of a fibrogenic cytokine.
AB  - Duchenne muscular dystrophy is a fatal disorder characterized by progressive
      muscular weakness, wasting, and severe muscle contractures in later disease
      stages. Muscle biopsy reveals conspicuous myofiber degeneration and fibrosis
      substituting muscle tissue. We quantitatively determined mRNA of the potent
      fibrogenic cytokine transforming growth factor-beta 1 by quantitative PCR in 15
      Duchenne muscular dystrophy, 13 Becker muscular dystrophy, 11 spinal muscular
      atrophy patients, and 16 controls. Higher transforming growth factor-beta 1
      expression was greater in Duchenne muscular dystrophy patients than controls (P =
      0.012) and Becker patients (P = 0.03). Fibrosis was significantly more prominent
      in Duchenne muscular dystrophy than Becker muscular dystrophy, spinal muscular
      atrophy, and controls. The proportion of connective tissue in muscle biopsies
      increased progressively with age in Duchenne muscular dystrophy patients, while
      transforming growth factor-beta 1 levels peaked at 2 and 6 yr of age.
      Transforming growth factor-beta 1 protein was also detected by
      immunocytochemistry and immunoblotting. Our findings suggest that transforming
      growth factor-beta 1 stimulates fibrosis in Duchenne muscular dystrophy.
      Expression of transforming growth factor-beta 1 in the early stages of Duchenne
      muscular dystrophy may be critical in initiating muscle fibrosis and antifibrosis
      treatment could slow progression of the disease, increasing the utility of gene
      therapy.

PMID- 7635951
TI  - Sickle erythrocytes, after sickling, regulate the expression of the endothelin-1
      gene and protein in human endothelial cells in culture.
AB  - The molecular defect in sickle cell disease resides in the beta globin gene, with
      consequent defects in erythrocytes only, suggesting that the vascular occlusion
      and vasomotor instability which characterize this disease are the result of
      interactions between abnormal sickle erythrocytes and cells of the blood vessel
      wall. We explored whether sickle erythrocytes may have effects on vascular tone,
      exclusive of adhesion events. Exposure of human endothelial cells in culture to
      previously sickled sickle erythrocytes resulted in a four to eight-fold
      transcriptional induction of the gene encoding the potent vasoconstrictor
      endothelin-1 (ET-1). Unsickled sickle erythrocytes or normal erythrocytes exposed
      to "sickling" conditions had no effect on ET-1 gene induction. Contact of the
      sickled erythrocytes with the endothelium was not required. Elevations in the ET
      1 transcript peaked at 3 h after exposure and persisted for up to 24 h. Four to
      sixfold increases in the amount of ET-1 peptide was released into the medium
      surrounding the endothelial cells after exposure to sickled sickle erythrocytes.
      This is the first demonstration of the regulation of gene expression in
      endothelial cells as a result of interaction with sickle cells, with induction of
      genes encoding vasoconstrictors. Furthermore, these findings suggest that sickle
      erythrocytes may have the capacity to affect local vasomotor tone directly.

PMID- 7635952
TI  - Adenovirus-mediated expression of a voltage-gated potassium channel in vitro (rat
      cardiac myocytes) and in vivo (rat liver). A novel strategy for modifying
      excitability.
AB  - Excitability is governed primarily by the complement of ion channels in the cell
      membrane that shape the contour of the action potential. To modify excitability
      by gene transfer, we created a recombinant adenovirus designed to overexpress a
      Drosophila Shaker potassium channel (AdShK). In vitro, a variety of mammalian
      cell types infected with AdShK demonstrated robust expression of the exogenous
      channel. Spontaneous action potentials recorded from cardiac myocytes in primary
      culture were abbreviated compared with noninfected myocytes. Intravascular
      infusion of AdShK in neonatal rats induced Shaker potassium channel mRNA
      expression in the liver, and large potassium currents could be recorded from
      explanted hepatocytes. Thus, recombinant adenovirus technology has been used for
      in vitro and in vivo gene transfer of ion channel genes designed to modify
      cellular action potentials. With appropriate targeting, such a strategy may be
      useful in gene therapy of arrhythmias, seizure disorders, and myotonic muscle
      diseases.

PMID- 7635953
TI  - Neurovascular dysfunction in diabetic rats. Potential contribution of
      autoxidation and free radicals examined using transition metal chelating agents.
AB  - Oxygen free radical activity is elevated in diabetes mellitus and has been
      implicated in the etiology of vascular complications. Recent studies have shown
      that impaired perfusion of nerve endoneurium is a major cause of nerve fiber
      dysfunction in experimental diabetes. Free radical scavenger treatment prevents
      the development of nerve conduction abnormalities in diabetic rats. In vitro
      experiments suggest that autoxidation reactions of glucose, catalyzed by free
      transition metal ions, are a potential source of free radicals in diabetes. We
      investigated whether chronic treatment with deferoxamine and trientine,
      transition metal chelating agents which can prevent autoxidation, could correct
      nerve conduction and blood flow changes in streptozotocin-diabetic rats. A 20%
      reduction in sciatic nerve motor conduction velocity after 2 mo diabetes was 90%
      ameliorated by 2 wk of treatment with deferoxamine or trientine. Sciatic
      endoneurial nutritive blood flow was 45% reduced by diabetes, but was completely
      corrected by treatment. In contrast, transition metal chelation had no effect on
      blood flow or conduction velocity in nondiabetic rats. Thus, the data support the
      hypothesis that increased free radical activity by glucose autoxidation as a
      result of impaired transition metal handling is a major cause of early
      neurovascular deficits in diabetes.

PMID- 7635954
TI  - Two receptor systems are involved in the plasma clearance of tissue-type
      plasminogen activator (t-PA) in vivo.
AB  - Tissue-type plasminogen activator (t-PA) is a serine protease, catalyzing the
      initial step in the fibrinolytic process. Intravenously administered t-PA is
      rapidly cleared from the circulation by the liver. Two distinct clearance
      mechanisms, which are mediated by the low density lipoprotein receptor-related
      protein (LRP) on liver parenchymal cells and by the mannose receptor on liver
      endothelial cells, have been described. Using competitors and inhibitors of the
      receptors, we investigated the role of LRP and carbohydrate receptors in t-PA
      clearance in vivo. To inhibit LRP, the 39-kD protein, which is a potent inhibitor
      of LRP activity, was overexpressed in the liver of mice using an adenoviral gene
      transfer technique. Expression of the 39-kD protein resulted in a sustained
      plasma concentration and an increase in the plasma half-life of 125I-t-PA from
      less than 1 min to 4-5 min. Blockade of the mannose receptor by intravenous
      administration of ovalbumin also prolonged the plasma half-life of 125I-t-PA to 3
      4 min. The same degree of inhibition of t-PA clearance was also observed after
      administration of an inhibitor of the fucose receptor, fucosyl-BSA. However,
      under the conditions established for the complete blockade of the mannose
      receptor, no additional inhibition of t-PA clearance was observed using fucosyl
      BSA, suggesting little or no role for the fucose receptor in the clearance of t
      PA. Furthermore, a dramatic increase of the plasma half-life of 125I-t-PA (>> 20
      min) was observed in mice overexpressing 39-kD protein and administered ovalbumin
      +/- fucosyl-BSA. Our results clearly demonstrate that two independent receptor
      systems, LRP and the mannose receptor, are involved in the hepatic clearance of t
      PA.

PMID- 7635956
TI  - Correction: A unique ectonucleotide pyrophosphohydrolase associated with porcine
      chondrocyte-derived vesicles.

PMID- 7635955
TI  - Nuclear factor-kappa B interacts functionally with the platelet-derived growth
      factor B-chain shear-stress response element in vascular endothelial cells
      exposed to fluid shear stress.
AB  - Hemodynamic forces, such as fluid shear stress, that act on the endothelial
      lining of the cardiovascular system can modulate the expression of an expanding
      number of genes crucial for homeostasis and the pathogenesis of vascular disease.
      A 6-bp core element (5'-GAGACC-3'), defined previously as a shear-stress response
      element is present in the promoters of many genes, including the PDGF B-chain,
      whose expression is modulated by shear stress. The identity of the nuclear
      protein(s) binding to this element has not yet been elucidated. Using
      electrophoretic mobility shift assays and in vitro DNase I footprinting, we
      demonstrate that nuclear factor-kappa B p50-p65 heterodimers, which accumulate in
      the nuclei of cultured vascular endothelial cells exposed to fluid shear stress,
      bind to the PDGF-B shear-stress response element in a specific manner. Mutation
      of this binding motif abrogated its interaction with p50-p65 and abolished the
      ability of the promoter to mediate increased gene expression in endothelial cells
      exposed to shear stress. Transient cotransfection studies indicate that p50-p65
      is able to activate PDGF-B shear-stress response element-dependent reporter gene
      expression in these cells. These findings thus implicate nuclear factor-kappa B
      in the transactivation of an endothelial gene responding to a defined fluid
      mechanical force.

PMID- 7635957
TI  - Fibrosis linked to TGF-beta in yet another disease.

PMID- 7635958
TI  - Rat kidney thromboxane receptor: molecular cloning, signal transduction, and
      intrarenal expression localization.
AB  - Thromboxane (TX) plays important roles in control of renal hemodynamics and water
      and electrolyte metabolism, and is involved in the pathophysiology of many renal
      diseases. The aim of the present study is to isolate a rat kidney cDNA encoding
      functional TX receptor, and to reveal its intrarenal expression localization. A
      clone (rTXR2) was isolated from a rat kidney cDNA library by a homology screening
      approach. rTXR2 was shown to encode the amino acid sequence containing seven
      transmembrane spanning domains representing rat (r) TX receptor. The membrane
      from COS-7 cells transiently transfected with rTXR2 cDNA was shown to be
      specifically bound by a thromboxane receptor antagonist, SQ29548. Either in
      Xenopus oocyte expression or in transfected COS-7 cells, rTX receptor was shown
      to be linked with Ca2+ messenger system. TX receptor-mediated increase in
      cytosolic Ca2+ was also observed in cultured glomerular mesangial cells. In situ
      hybridization showed that rTX receptor mRNA was detected in renal glomeruli,
      smooth muscle cells in renal arterioles, and transitional cell epithelium of
      renal pelvis. Reverse transcription linked to PCR applied to microdissected
      nephron segments indicated the presence of rTX receptor mRNA exclusively in the
      glomerulus. In conclusion, we have cloned a functional rat kidney TX receptor,
      which is expressed specifically in renal glomerulus, arterial smooth muscle
      cells, and transitional cell epithelium of renal pelvis. The present study will
      provide important insights into the etiology and pathophysiology of renal
      diseases with relation to TX metabolism.

PMID- 7635960
TI  - The importance of a lipopolysaccharide-initiated, cytokine-mediated host defense
      mechanism in mice against extraintestinally invasive Escherichia coli.
AB  - Extraintestinally invasive Escherichia coli (EC) that possess both a complete LPS
      and K1 capsule evade both complement-mediated bacteriolysis and neutrophil
      mediated killing. Since C3H/HeJ mice that are hyporesponsive to LPS were uniquely
      susceptible to lethal infection with EC of this phenotype, we speculated there
      was an LPS-initiated host defense mechanism against this pathogenic phenotype.
      The LPS-normoresponsive C3H/HeN as well as the C3H/HeJ mice cleared these EC from
      the circulation within 4 h of intravenous administration. Whereas electron
      micrographs of the liver demonstrated these EC undergoing degeneration within the
      phagolysosomes of of both macrophages and Kupffer cells of C3H/HeN mice, these EC
      replicated within these cells of the C3H/HeJ mice. Restoration of anti-EC
      activity of C3H/HeJ mice occurred with activation of Kupffer cells and peritoneal
      macrophages in vivo with BCG and in vitro with IFN-gamma, but not with LPS.
      Pretreatment of C3H/HeJ mice with a combination of recombinant murine IL-1 and
      TNF-alpha also restored the killing of K1(+)-EC but did not enhance the killing
      of a K1(-)-EC mutant. These data are consistent with the hypothesis that (a)
      there is no intrinsic inability of C3H/HeJ phagocytes to kill EC, but (b) an LPS
      initiated, cytokine-mediated host defense mechanism is required for such killing.
      These studies emphasize the importance of bacterial surface characteristics in
      the interaction with specific host defenses.

PMID- 7635961
TI  - Linkage of the angiotensinogen gene locus to human essential hypertension in
      African Caribbeans.
AB  - The renin-angiotensin system regulates blood pressure and sodium balance. The
      angiotensinogen gene which encodes the key substrate within this system has been
      linked to essential hypertension in White Europeans. It has been suggested that
      people of West African ancestry may have a different genetic basis for
      hypertension. In this study we have tested whether there is linkage of the
      angiotensinogen gene to essential hypertension in African Caribbeans from St.
      Vincent and the Grenadines. DNA from 63 affected sibling pairs with hypertension
      was tested for linkage by analyzing whether there was excess allele sharing among
      siblings genotyped using an angiotensinogen dinucleotide repeat sequence. There
      was significant support for linkage (T = 3.07, P = 0.001) and association of this
      locus to hypertension (chi 2 = 50.2, 12 degrees of freedom, P << 0.001). A DNA
      polymorphism which alters methionine to threonine at position 235 (M235T) within
      the angiotensinogen peptide has been associated previously with hypertension.
      However, we found no association of this variant with hypertension in this study.
      These findings provide support for linkage and association of the angiotensinogen
      locus to hypertension in African Caribbeans and suggest some similarities in the
      genetic basis of essential hypertension in populations of different ethnicity.

PMID- 7635959
TI  - Effect of glucagon on intracellular pH regulation in isolated rat hepatocyte
      couplets.
AB  - To elucidate mechanisms of glucagon-induced bicarbonate-rich choleresis, we
      investigated the effect of glucagon on ion transport processes involved in the
      regulation of intracellular pH (pHi) in isolated rat hepatocyte couplets. It was
      found that glucagon (200 nM), without influencing resting pHi, significantly
      stimulates the Cl-/HCO3- exchange activity. The effect of glucagon was associated
      with a sevenfold increase in cAMP levels in rat hepatocytes. The activity of the
      Cl-/HCO3- exchanger was also stimulated by DBcAMP + forskolin. The effect of
      glucagon on the Cl-/HCO3- exchange was individually blocked by two specific and
      selective inhibitors of protein kinase A, Rp-cAMPs (10 microM) and H-89 (30
      microM), the latter having no influence on the glucagon-induced cAMP accumulation
      in isolated rat hepatocytes. The Cl- channel blocker, NPPB (10 microM), showed no
      effect on either the basal or the glucagon-stimulated Cl-/HCO3 exchange. In
      contrast, the protein kinase C agonist, PMA (10 microM), completely blocked the
      glucagon stimulation of the Cl-/HCO3- exchange; however, this effect was achieved
      through a significant inhibition of the glucagon-stimulated cAMP accumulation in
      rat hepatocytes. Colchicine pretreatment inhibited the basal as well as the
      glucagon-stimulated Cl-/HCO3- exchange activity. The Na+/H+ exchanger was
      unaffected by glucagon either at basal pHi or at acid pHi values. In contrast,
      glucagon, at basal pHi, stimulated the Na(+)-HCO3- symport. The main findings of
      this study indicate that glucagon, through the cAMP-dependent protein kinase A
      pathway, stimulates the activity of the Cl-/HCO3- exchanger in isolated rat
      hepatocyte couplets, a mechanism which could account for the in vivo induced
      bicarbonate-rich choleresis.

PMID- 7635962
TI  - A mutation in the dystrophin gene selectively affecting dystrophin expression in
      the heart.
AB  - We have previously shown in a large X-linked pedigree that a deletion removing
      the dystrophin muscle promoter, the first muscle exon and part of intron 1 caused
      a severe dilated cardiomyopathy with no associated muscle weakness. Dystrophin
      expression was present in the muscle of affected males and transcription studies
      indicated that this dystrophin originated from the brain and Purkinje cell
      isoforms, upregulated in this skeletal muscle. We have now studied dystrophin
      transcription and expression in the heart of one member of this family. In
      contrast to the skeletal muscle, dystrophin transcription and expression were
      absent in the heart, with the exception of the distal Dp71 dystrophin isoform,
      normally present in the heart. The 43- and 50-kD dystrophin-associated proteins
      were severely reduced in the heart, despite the presence of Dp71, but not in
      skeletal muscle. The absence of dystrophin and the down-regulation of the
      dystrophin-associated proteins in the heart accounted for the severe
      cardiomyopathy in this family. The mutation present in these males selectively
      affects dystrophin expression in the heart; this could be secondary to the
      removal of cardiac-specific regulatory sequences. This family may represent the
      first example of a mutation specifically affecting the cardiac expression of a
      gene, present physiologically in both the skeletal and cardiac muscles.

PMID- 7635963
TI  - Adenovirus-mediated transfer of a gene encoding cholesterol 7 alpha-hydroxylase
      into hamsters increases hepatic enzyme activity and reduces plasma total and low
      density lipoprotein cholesterol.
AB  - Clinical interventions that accelerate conversion of cholesterol to bile acids
      reduce circulating low density lipoprotein (LDL) cholesterol concentrations. The
      initial and rate-limiting step in the bile acid biosynthetic pathway is catalyzed
      by hepatic cholesterol 7 alpha-hydroxylase. To examine the effects of transient
      primary overexpression of this enzyme on sterol metabolism and lipoprotein
      transport, we constructed a recombinant adenovirus in which a cDNA encoding rat 7
      alpha-hydroxylase is expressed from the human cytomegalovirus immediate-early
      promoter (AdCMV7 alpha). Syrian hamsters administered AdCMV7 alpha intravenously
      accumulated transgene-specific mRNA in the liver and demonstrated a dose
      dependent increase in hepatic microsomal 7 alpha-hydroxylase activity. The
      increased conversion of cholesterol to bile acids resulted in a compensatory
      increase in hepatic cholesterol synthesis. In addition, overexpression of 7 alpha
      hydroxylase reduced the rate of LDL cholesterol entry into the plasma space and,
      in animals maintained on a Western-type diet, restored hepatic LDL receptor
      expression. As a consequence, plasma LDL concentrations fell by approximately 60%
      in animals maintained on control diet and by approximately 75% in animals
      consuming a Western-type diet. Plasma high density lipoprotein cholesterol levels
      were reduced to a lesser degree. These results demonstrate that transient
      upregulation of bile acid synthesis by direct transfer of a 7 alpha-hydroxylase
      gene favorably alters circulating lipoprotein profiles and suggest one potential
      molecular target for genetic strategies aimed at reducing cardiovascular risk.

PMID- 7635965
TI  - Impairment of glucose-induced insulin secretion in human pancreatic islets
      transplanted to diabetic nude mice.
AB  - Hyperglycemia-induced beta-cell dysfunction may be an important component in the
      pathogenesis of non-insulin-dependent diabetes mellitus. However, most available
      data in this field were obtained from rodent islets. To investigate the relevance
      of this hypothesis for human beta-cells in vivo, human pancreatic islets were
      transplanted under the renal capsule of nude mice. Experimental groups were
      chosen so that grafted islets were exposed to either hyper- or normoglycemia or
      combinations of these for 4 or 6 wk. Grafts of normoglycemic recipients responded
      with an increased insulin release to a glucose stimulus during perfusion, whereas
      grafts of hyperglycemic recipients failed to respond to glucose. The insulin
      content of the grafts in the latter groups was only 10% of those observed in
      controls. Recipients initially hyperglycemic (4 wk), followed by 2 wk of
      normoglycemia regained a normal graft insulin content, but a decreased insulin
      response to glucose remained. No ultrastructural signs of beta-cell damage were
      observed, with the exception of increased glycogen deposits in animals
      hyperglycemic at the time of killing. It is concluded that prolonged exposure to
      a diabetic environment induces a long-term secretory defect in human beta-cells,
      which is not dependent on the size of the islet insulin stores.

PMID- 7635964
TI  - Zonula occludens toxin modulates tight junctions through protein kinase C
      dependent actin reorganization, in vitro.
AB  - The intracellular signaling involved in the mechanism of action of zonula
      occludens toxin (ZOT) was studied using several in vitro and ex vivo models. ZOT
      showed a selective effect among various cell lines tested, suggesting that it may
      interact with a specific receptor, whose surface expression on various cells
      differs. When tested in IEC6 cell monolayers, ZOT-containing supernatants induced
      a redistribution of the F-actin cytoskeleton. Similar results were obtained with
      rabbit ileal mucosa, where the reorganization of F-actin paralleled the increase
      in tissue permeability. In endothelial cells, the cytoskeletal rearrangement
      involved a decrease of the soluble G-actin pool (-27%) and a reciprocal increase
      in the filamentous F-actin pool (+22%). This actin polymerization was time- and
      dose-dependent, and was reversible. Pretreatment with a specific protein kinase C
      inhibitor, CGP41251, completely abolished the ZOT effects on both tissue
      permeability and actin polymerization. In IEC6 cells ZOT induced a peak increment
      of the PKC-alpha isoform after 3 min incubation. Taken together, these results
      suggest that ZOT activates a complex intracellular cascade of events that
      regulate tight junction permeability, probably mimicking the effect of
      physiologic modulator(s) of epithelial barrier function.

PMID- 7635966
TI  - Identification of the mechanism for the inhibition of Na+,K(+)-adenosine
      triphosphatase by hyperglycemia involving activation of protein kinase C and
      cytosolic phospholipase A2.
AB  - Inhibition of Na+,K(+)-ATPase activity by hyperglycemia could be an important
      etiological factor of chronic complications in diabetic patients. The biochemical
      mechanism underlying hyperglycemia's inhibitory effects has been thought to
      involve the alteration of the protein kinase C (PKC) pathway since agonists of
      PKC can normalize hyperglycemia-induced inhibition of Na+,K(+)-ATPase activity.
      Paradoxically, elevated glucose levels and diabetes have been shown to increase
      PKC activities in vascular cells. The present study tested the hypothesis that
      the inhibition of Na+,K(+)-ATPase activity is mediated by the sequential
      activation of PKC and cytosolic phospholipase A2 (cPLA2). In cultured rat
      vascular smooth muscle cells (VSMC), increasing glucose levels in the medium from
      5.5 to 22 mM elevated cPLA2 activity and increased [3H]arachidonic acid release
      and PGE2 production by 2.3-, 1.7- and 2-fold, respectively. Similar increases in
      cPLA2 activity were also induced by elevated glucose levels in human VSMC and rat
      capillary endothelial cells. The activation of cPLA2 was mediated by PKC since
      the increases in cPLA2 phosphorylation and enzymatic activity were inhibited by
      the PKC inhibitor GFX. In contrast, elevation of glucose levels decreased
      Na+,K(+)-ATPase activity as measured by ouabain-sensitive 86Rb uptake by twofold
      in rat VSMC. Surprisingly, both PMA, a PKC agonist, and GFX, a PKC inhibitor,
      were able to prevent glucose-induced decreases in 86Rb uptake. Further, the PLA2
      inhibitor AACOCF3 abolished both glucose-induced activation of cPLA2 and the
      decrease in 86Rb uptake. These data indicated that hyperglycemia is inhibiting
      Na+,K(+)-ATPase activity by the sequential activation of PKC and cPLA2, resulting
      in the liberation of arachidonic acid and increased the production of PGE2, which
      are known inhibitors of Na+,K(+)-ATPase.

PMID- 7635968
TI  - Purification and partial sequencing of the major mitogen for human uterine smooth
      muscle-like cells in leiomyoma extracts.
AB  - We purified the major mitogen for human smooth muscle-like cells in leiomyoma
      extracts by sequential liquid chromatography on (a) carboxymethyl-Sepharose, (b)
      heparin-Sepharose columns, (c) cartridges of C18 silica, and (d) linear gradient
      reverse-phase high performance liquid chromatography. The mitogenic activity of
      the leiomyoma extract throughout purification was tested by tritiated thymidine
      incorporation and DNA content in NIH/3T3 fibroblasts and KW human smooth muscle
      like cells. Purification of the leiomyoma-derived growth factor (LDGF) for KW
      smooth muscle-like cells confirmed that its partial NH2-terminal amino acid (aa)
      sequence (1-20 aa) was identical to 113-132 aa of the human cysteine-rich protein
      (hCRP). A synthetic peptide which was engineered based on the purified aa
      sequence, stimulated the proliferation and growth of KW cells. An oligonucleotide
      probe constructed by the cDNA of the hcrp gene that encodes this aa sequence
      depicted the expression of 1.9-kb LDGF mRNA in leiomyomas and myometrium. The
      expression of the LDGF mRNA was three to sixfold higher in leiomyomas compared
      with adjacent myometrium of women harboring leiomyomas by in situ hybridization
      analysis. These data suggest that LDGF may participate in the pathophysiology of
      uterine leiomyomas.

PMID- 7635969
TI  - Enhanced G protein activation in immortalized lymphoblasts from patients with
      essential hypertension.
AB  - Epstein-Barr virus-immortalized B lymphoblasts obtained from hypertensive
      patients with enhanced Na+/H+ exchanger activity (HT cells) proliferate
      distinctly faster upon serum stimulation than those from normotensive controls
      with low exchanger activity (NT cells) (Rosskopf, D., E. Fromter, and W. Siffert.
      1993. J. Clin. Invest. 92:2553-2559). Stimulation with platelet-activating factor
      (PAF) as well caused an enhanced proliferation of HT cells. In analyzing possible
      differences in signal transduction between the immortalized NT and HT
      lymphoblasts, we observed that cell stimulation with PAF and somatostatin caused
      a twofold higher increase in [Ca2+]i in HT than in NT cell lines. This difference
      was completely abrogated by pertussis toxin (PTX) treatment. Furthermore, PAF
      stimulated formation of inositol 1,4,5-trisphosphate (IP3) was twofold enhanced
      in HT cell lines. On the other hand, PAF receptor density and affinity, total
      cellular phospholipase C activity, expression of PTX-sensitive G proteins, and
      control binding of the stable GTP analogue, guanosine 5'-[gamma-thio]triphosphate
      (GTP gamma S), to membrane G proteins were not different in NT and HT cell lines.
      However, PAF- and mastoparan-stimulated binding of GTP gamma S to G proteins,
      which was fully PTX-sensitive, was 2.5-fold higher in HT than NT cell lines.
      These data suggest an enhanced receptor-mediated activation of PTX-sensitive G
      proteins despite unchanged receptor and G protein expression. Thus, this study
      not only suggests that enhanced signal transduction and cell proliferation are
      abnormalities in a certain group of patients with essential hypertension but also
      explains these findings as a result of an enhanced G protein activation in this
      common disorder.

PMID- 7635971
TI  - Identification of an idiotypic peptide recognized by autoantibodies in human
      immunodeficiency virus-1-infected individuals.
AB  - Antibodies against HIV-1 proteins in HIV-1-infected individuals share a cross
      reactive idiotype defined by the monoclonal antiidiotypic antibody 1F7 (5). Using
      a computer algorithm based on the molecular recognition theory, regions of
      inverse hydropathy between the variable sequence of 1F7 and human monoclonal anti
      HIV-1 antibodies were identified, which are assumed to be involved in idiotype
      antiidiotype contacts. A peptide was designed from the proposed contact in the
      variable heavy chain framework 3-complementarity determining region 3 (FR3-CDR3)
      of human antibodies and was synthesized. This peptide is recognized by the
      antiidiotype 1F7 and inhibits the binding of 1F7 to human anti-HIV-1 antibodies
      which express the 1F7 idiotype. A survey of normal and HIV-1-infected sera
      revealed the presence of antibodies in infected sera which bind to the FR3-CDR3
      peptide. The biological relevance of autoantibodies against a self idiotope
      associated with HIV-1 infection is discussed in the context of the regulation of
      the antibody response to HIV-1.

PMID- 7635970
TI  - Parathyroid hormone increases the concentration of insulin-like growth factor-I
      and transforming growth factor beta 1 in rat bone.
AB  - Intermittent treatment with parathyroid hormone (PTH) increases bone mass in
      experimental animals and humans. In vitro studies have suggested that the
      anabolic effect of PTH may be mediated by local growth factors. However, the
      relevance of these findings to in vivo situations remains unclear. In this study,
      we examined a time course of daily s.c. injections of hPTH (1-34) on the skeletal
      concentration of insulin-like growth factor (IGF)-I, IGF-II, and transforming
      growth factor beta (TGF-beta) in the proximal tail vertebrae of male rats. PTH
      caused a time and dose-dependent increase in the bone mineral density of the
      lumbar spine. This anabolic effect on bone mass was accompanied by progressive
      increases in bone matrix-associated IGF-I and TGF-beta 1. Increases in IGF-I and
      TGF-beta 1 became apparent after four and eight weeks of PTH treatment
      respectively and persisted through week 12. PTH had no effect on circulating IGF
      I, suggesting that the increase of bone matrix IGF-I was due to the local effect
      of PTH on bone tissue directly rather than to an increase of circulating IGF-I.
      These data are consistent with the hypothesis that IGF-I and TGF-beta 1 may play
      a role as local mediators of the anabolic effects of PTH on bone metabolism.

PMID- 7635967
TI  - Fibrates increase human apolipoprotein A-II expression through activation of the
      peroxisome proliferator-activated receptor.
AB  - In view of the evidence linking plasma high density lipoprotein (HDL)-cholesterol
      levels to a protective effect against coronary artery disease and the widespread
      use of fibrates in the treatment of hyperlipidemia, the goal of this study was to
      analyze the influence of fibrates on the expression of apolipoprotein (apo) A-II,
      a major protein constituent of HDL. Administration of fenofibrate (300 mg/d) to
      16 patients with coronary artery disease resulted in a marked increase in plasma
      apo A-II concentrations (0.34 +/- 0.11 to 0.45 +/- 0.17 grams/liter; P < 0.01).
      This increase in plasma apo A-II was due to a direct effect on hepatic apo A-II
      production, since fenofibric acid induced apo A-II mRNA levels to 450 and 250% of
      control levels in primary cultures of human hepatocytes and in human
      hepatoblastoma HepG2 cells respectively. The induction in apo A-II mRNA levels
      was followed by an increase in apo A-II secretion in both cell culture systems.
      Transient transfection experiments of a reporter construct driven by the human
      apo A-II gene promoter indicated that fenofibrate induced apo A-II gene
      expression at the transcriptional level. Furthermore, several other peroxisome
      proliferators, such as the fibrate, Wy-14643, and the fatty acid,
      eicosatetraynoic acid (ETYA), also induced apo A-II gene transcription.
      Unilateral deletions and site-directed mutagenesis identified a sequence element
      located in the J-site of the apo A-II promoter mediating the responsiveness to
      fibrates and fatty acids. This element contains two imperfect half sites spaced
      by 1 oligonucleotide similar to a peroxisome proliferator responsive element
      (PPRE). Cotransfection assays showed that the peroxisome proliferator activated
      receptor (PPAR) transactivates the apo A-II promoter through this AII-PPRE. Gel
      retardation assays demonstrated that PPAR binds to the AII-PPRE with an affinity
      comparable to its binding affinity to the acyl coA oxidase (ACO)-PPRE. In
      conclusion, in humans fibrates increase plasma apo A-II concentrations by
      inducing hepatic apo A-II production. Apo A-II expression is regulated at the
      transcriptional level by fibrates and fatty acids via the interaction of PPAR
      with the AII-PPRE, thereby demonstrating the pivotal role of PPAR in controlling
      human lipoprotein metabolism.

PMID- 7635972
TI  - Congenital human thyroglobulin defect due to low expression of the thyroid
      specific transcription factor TTF-1.
AB  - TTF-1 and Pax-8 are thyroid-specific transcription factors, from homeo and paired
      box genes, respectively, that are responsible for thyroid development and for
      thyroglobulin and thyroperoxidase gene expression. However, TTF-1 and Pax-8
      preferentially bind to the thyroglobulin and thyroperoxidase promoters,
      respectively. Here, we have studied a patient with defective thyroglobulin
      synthesis. Thyroglobulin mRNA was found at very low levels while the mRNA for
      thyroperoxidase was found to be more abundant compared with control tissue. The
      low levels of thyroglobulin mRNA are caused by a transcriptional defect due to
      the virtual absence of TTF-1 expression as determined by Northern blot analysis,
      reverse transcriptase-PCR, and electrophoretic mobility shift assays. The level
      of Pax-8 mRNA was the same in the goiter and in the control thyroid. These
      results are the first reported evidence of a congenital goiter with a
      thyroglobulin synthesis defect due to the low expression of the thyroid-specific
      transcription factor TTF-1. Moreover, these data suggest that TTF-1 and Pax-8
      would be differentially regulating thyroglobulin and thyroperoxidase gene
      transcription.

PMID- 7635973
TI  - Insulin-mediated skeletal muscle vasodilation contributes to both insulin
      sensitivity and responsiveness in lean humans.
AB  - Whether insulin-mediated vasodilation is important in determining insulin's
      overall action to stimulate glucose uptake is unknown. To this end, we measured
      leg glucose uptake during euglycemic hyperinsulinemic clamps performed at two
      insulin doses (40 mU/m2 per min, n = 6 and 120 mU/m2 per min, n = 15) alone and
      during a superimposed intrafemoral artery infusion of GN-monomethyl-L-arginine (L
      NMMA) designed to blunt insulin-mediated vasodilation. During the higher dose
      study, hyperinsulinemia resulted in about a twofold rise in basal leg blood flow
      from 0.24 +/- 0.02 to 0.45 +/- 0.05 liter/min, P < 0.0001. L-NMMA infusion
      resulted in a net 21% reduction in leg glucose uptake from 114 +/- 18 mg/min to
      85 +/- 13 mg/min, P < 0.001. We also found a significant relationship between the
      rate of insulin-stimulated whole body glucose uptake and the magnitude of flow
      dependent glucose uptake (r = 0.57, P = 0.02). Data obtained during the lower
      dose insulin infusion resulted in similar findings. In conclusion, in healthy
      lean subjects, insulin-stimulated muscle blood flow contributes to both insulin
      responsiveness and insulin sensitivity. The most insulin-sensitive subjects
      appear to be the most reliant on muscle perfusion for insulin action. Insulin
      mediated vasodilation is an important physiological determinant of insulin
      action.

PMID- 7635974
TI  - Deleterious effects of calcium channel blockade on pressure transmission and
      glomerular injury in rat remnant kidneys.
AB  - Hypertensive mechanisms are postulated to play a major role in the progressive
      glomerulosclerosis (GS) after renal mass reduction. But, in contrast to
      converting enzyme inhibitors, BP reduction by calcium channel blockers, has not
      provided consistent protection. Radiotelemetric BP monitoring for 7 wk was used
      to compare nifedipine (N) and enalapril (E) in the rat approximately 5/6 renal
      ablation model. After the first week, rats received N, E, or no treatment (C).
      The overall averaged systolic BP in C (173 +/- 7 mmHg) was reduced by both E and
      N (P < 0.001), but E was more effective (113 +/- 2 vs. 134 +/- 3 mmHg, P < 0.01).
      GS was prevented by E (2 +/- 1 vs. 26 +/- 5% in C) but not by N (25 +/- 6%). GS
      correlated well with the overall averaged BP in individual animals of all groups,
      but the slope of the relationship was significantly steeper in N compared with
      C+E rats (P < 0.02), suggesting greater pressure transmission to the glomeruli
      and GS for any given BP. Since autoregulatory mechanisms provide the primary
      protection against pressure transmission, renal autoregulation was examined at 3
      wk in additional rats. Autoregulation was impaired in C rats, was not
      additionally altered by E, but was completely abolished by N. These data
      demonstrate the importance of autoregulatory mechanisms in the pathogenesis of
      hypertensive injury and suggest that calcium channel blockers which adversely
      affect pressure transmission may not provide protection despite significant BP
      reduction.

PMID- 7635975
TI  - Excessive insulin receptor serine phosphorylation in cultured fibroblasts and in
      skeletal muscle. A potential mechanism for insulin resistance in the polycystic
      ovary syndrome.
AB  - We investigated the cellular mechanisms of the unique disorder of insulin action
      found in the polycystic ovary syndrome (PCOS). Approximately 50% of PCOS women
      (PCOS-Ser) had a significant increase in insulin-independent beta-subunit
      [32P]phosphate incorporation (3.7-fold, P < 0.05 vs other groups) in skin
      fibroblast insulin receptors that was present in serine residues while insulin
      induced tyrosine phosphorylation was decreased (both P < 0.05 vs other groups).
      PCOS skeletal muscle insulin receptors had the same abnormal phosphorylation
      pattern. The remaining PCOS women (PCOS-n1) had basal and insulin-stimulated
      receptor autophosphorylation similar to control. Phosphorylation of the
      artificial substrate poly GLU4:TYR1 by the PCOS-Ser insulin receptors was
      significantly decreased (P < 0.05) compared to control and PCOS-n1 receptors. The
      factor responsible for excessive serine phosphorylation appeared to be extrinsic
      to the receptor since no insulin receptor gene mutations were identified,
      immunoprecipitation before autophosphorylation corrected the phosphorylation
      defect and control insulin receptors mixed with lectin eluates from affected PCOS
      fibroblasts displayed increased serine phosphorylation. Our findings suggest that
      increased insulin receptor serine phosphorylation decreases its protein tyrosine
      kinase activity and is one mechanism for the post-binding defect in insulin
      action characteristic of PCOS.

PMID- 7635976
TI  - Evidence of a role for GTP in the potentiation of Ca(2+)-induced insulin
      secretion by glucose in intact rat islets.
AB  - Glucose initiates insulin secretion by closing K(+)-ATP channels, leading to Ca2+
      influx (E1); it also potentiates Ca(2+)-induced secretion (E2) when the K(+)-ATP
      channel is kept open using diazoxide and depolarizing concentrations of K+ are
      provided. To examine the roles of purine nucleotides in E2, we compared the
      effects of glucose to those of the mitochondrial fuel monomethylsuccinate. Either
      agonist could induce E2 accompanied by significant increases in ATP, ATP/ADP
      ratio, and GTP/GDP ratio; GTP increased significantly only with glucose.
      Mycophenolic acid (MPA), an inhibitor of cytosolic GTP synthesis, markedly
      inhibited glucose-induced E2 (either in perifusions or in static incubations) and
      decreased GTP and the GTP/GDP ratio, but did not alter the ATP/ADP ratio.
      Provision of guanine (but not adenine) reversed these changes pari passu. In
      contrast, MPA had no effect on succinate-induced E2, despite generally similar
      changes in nucleotides. A similar lack of effect of MPA on E2 was seen with a
      second mitochondrial fuel, alpha-ketoisocaproic acid (KIC). However, in the
      absence of diazoxide and K+, MPA blunted the secretory effects of either glucose,
      succinate, or KIC. These studies suggest that GTP plays a role in both glucose
      and succinate or KIC-induced insulin secretion at a step dependent on
      mitochondrial metabolism and the K(+)-ATP channel. In addition to mitochondrial
      effects, glucose appears to have extramitochondrial effects important to its
      potentiation of Ca(2+)-induced insulin secretion that are also dependent on GTP.

PMID- 7635978
TI  - Linoleic acid and its metabolites, hydroperoxyoctadecadienoic acids, stimulate c
      Fos, c-Jun, and c-Myc mRNA expression, mitogen-activated protein kinase
      activation, and growth in rat aortic smooth muscle cells.
AB  - Previous studies from other laboratories suggest that linoleic acid and its
      metabolites, hydroperoxyoctadecadienoic acids, play an important role in
      modulating the growth of some cells. A correlation has been demonstrated between
      hydroperoxyoctadecadienoic acids and conditions characterized by abnormal cell
      growth such as atherosclerosis and psoriasis. To determine if linoleic acid and
      its metabolites modulate cell growth in atherosclerosis, we measured DNA
      synthesis, protooncogene mRNA expression, and mitogen-activated protein kinase
      (MAPK) activation in vascular smooth muscle cells (VSMC). Linoleic acid induces
      DNA synthesis, c-fos, c-jun, and c-myc mRNA expression and MAPK activation in
      VSMC. Furthermore, nordihydroguaiaretic acid, a potent inhibitor of the
      lipoxygenase system, significantly reduced the growth-response effects of
      linoleic acid in VSMC, suggesting that conversion of linoleic acid to
      hydroperoxyoctadecadienoic acids (HPODEs) is required for these effects. HPODEs
      also caused significant induction of DNA synthesis, protooncogene mRNA
      expression, and MAPK activation in growth-arrested VSMC, suggesting that linoleic
      acid and its metabolic products, HPODEs, are potential mitogens in VSMC, and that
      conditions such as oxidative stress and lipid peroxidation which provoke the
      production of these substances may alter VSMC growth.

PMID- 7635979
TI  - Localization of the angiotensin II and its receptor subtype expression in human
      endometrium and identification of a novel high-affinity angiotensin II binding
      site.
AB  - Angiotensin (ANG) II is not only a potent vasoconstrictor but may also be
      involved in the regeneration of new blood vessels. In proliferative endometrium,
      ANG II-like immunoreactivity was detected in glandular epithelium and stroma with
      negligible staining around the vascular endothelium. In contrast, in secretory
      endometrium intense immunostaining was seen in the perivascular stromal cells
      around the endometrial spiral arterioles with negligible staining of the other
      cell types. Quantitative receptor autoradiography using the nonselective
      radioligand [125I]-ANG II and subtype selective competing compounds showed that
      endometrium contained predominantly AT2 receptors, with relatively low expression
      of AT1 receptors and a novel non-AT1/non-AT2 angiotensin II recognition site that
      was insensitive to AT1 or AT2 selective ligands. Levels of specific [125I]-ANG II
      receptor binding displayed cyclic changes during the menstrual cycle, reaching a
      maximum in early secretory endometrium and then decreasing in mid to late
      secretory endometrium to levels seen in early to mid proliferative endometrium.
      In situ hybridization showed AT1 receptor mRNA expression in the glands and in
      the endometrial blood vessels. The cyclic changes in ANG II-like immunoreactivity
      together with expression of both the known and the novel AT receptor subtypes
      imply that this octopeptide may play a dual role both in the control of the
      uterine vascular bed and also in the regeneration of the endometrium after
      endometrial shedding, acting as an angiogenic and mitogenic mediator.

PMID- 7635980
TI  - Favorable left ventricular remodeling following large myocardial infarction by
      exercise training. Effect on ventricular morphology and gene expression.
AB  - Continued adverse remodeling of myocardium after infarction may lead to
      progressive ventricular dilation and heart failure. We tested the hypothesis that
      exercise training in a healed myocardial infarction-dysfunction rat model can
      favorably modify the adverse effects of ventricular remodeling including
      attenuation of abnormal myosin gene expression. Sprague-Dawley rats were
      subjected to either proximal LAD ligation or sham operation. At 5 wk after the
      operation, animals were randomly assigned to sedentary conditions or 6 wk of
      graduated swim training, creating four experimental groups: infarct sedentary
      (IS), infarct exercise (IE), sham sedentary (SS), and sham exercise (SE). At 11
      wk all rats were sacrificed and analyzed. Compared to sedentary infarct controls,
      exercise training attenuated left ventricular (LV) dilation and allowed more
      hypertrophy of the non infarct wall. The exercise-trained hearts also showed a
      reduction in the estimated peak wall tension. Northern blot analysis showed an
      increase in beta-myosin heavy chain expression in the hearts of the sedentary
      infarction group soon after infarction when compared to sham controls. However,
      with exercise training, there was a significant attenuation of the beta-myosin
      heavy chain expression in the myocardium. Exercise training in a model of left
      ventricular dysfunction after healed myocardial infarction can improve the
      adverse remodeling process by attenuating ventricular dilation and reducing wall
      tension. The abnormal beta-myosin expression was also attenuated in the exercise
      trained group. This is evidence that abnormal gene expression following severe
      myocardial infarction dysfunction can be favorably modified by an intervention.

PMID- 7635977
TI  - Somatic mutation and CDR3 lengths of immunoglobulin kappa light chains expressed
      in patients with rheumatoid arthritis and in normal individuals.
AB  - Immunoglobulin secretion by plasma cells infiltrating synovial membranes is a
      prominent feature of RA. Previous analyses of a cDNA library generated from
      synovium of RA patient BC revealed immunoglobulin kappa light chain transcripts
      with extensive somatic mutation, frequent N region addition, and unexpected
      variation in the lengths of CDR3 regions which form the center of the antigen
      binding site. To determine if these characteristics are present in other
      individuals, we performed reverse transcription-polymerase chain reaction
      amplification and sequenced > or = 10 V kappa-containing amplicons from nine
      tissue samples: synovia of three individuals with long-standing RA (including
      patient BC), PBLs of two of these individuals, and PBLs or splenocytes of four
      normal individuals. Increased levels of somatic mutation in PBLs appeared to
      correlate with increased age, which may reflect accumulation of circulating
      memory cells and/or decreased bone marrow production of naive B lymphocytes. Two
      of three RA synovial samples and both RA PBL samples exhibited increased
      proportions of clones with unusual CDR3 lengths. Enrichment for these antibody
      binding sites could be due to abnormal regulation of the emerging repertoire or
      to selection for B lymphocytes bearing antibodies of unusual specificity, and may
      play a role in the pathogenesis of RA.

PMID- 7635981
TI  - ENV-specific cytotoxic T lymphocyte responses in HIV seronegative health care
      workers occupationally exposed to HIV-contaminated body fluids.
AB  - Identification of the components of protective immunity are crucial for the
      development of effective prophylactic and therapeutic vaccine strategies.
      Analysis of HIV-specific responses in exposed but uninfected individuals might
      thus provide a unique resource to elucidate the components and correlates of
      protective immunity to HIV. In the present study we analyzed HIV-specific
      cytotoxic and helper T lymphocyte responses in health care workers (HCW) exposed
      to body fluids from HIV-positive individuals. HCW exposed to blood from HIV
      negative individuals as well as healthy donors served as controls. Cytotoxic T
      lymphocyte (CTL) responses to HIV envelope (env) peptides were detected in 7/20
      (35%) HCW exposed to HIV-positive blood and in none of the 20 health care workers
      exposed to uninfected blood or the seven healthy blood donors studied. HIV
      specific CTL responses were detected only after in vitro stimulation, and were
      MHC class I restricted. No MHC class I restriction elements were uniformly
      identified among the different responders. 21/28 (75%) HCW exposed to
      contaminated blood responded to env as measured by IL-2 production to the
      peptides, in contrast to only 9/38 (24%) HCW exposed to HIV seronegative blood
      and 3/35 (9%) healthy blood donors. All the HIV exposed individuals were
      seronegative on repeated ELISA tests, and no evidence of infection was obtained
      by PCR analysis. These findings indicate that a single exposure to HIV can induce
      CTL immunity to HIV antigens, in the absence of other evidence of infection.

PMID- 7635982
TI  - Recognition of clonogenic leukemic cells, remission bone marrow and HLA-identical
      donor bone marrow by CD8+ or CD4+ minor histocompatibility antigen-specific
      cytotoxic T lymphocytes.
AB  - We investigated whether minor histocompatibility (mH) antigen-specific cytotoxic
      T lymphocytes (CTL) can discriminate between leukemic hematopoietic progenitor
      cells (leukemic-HPC) from AML or CML patients, the HPC from their remission bone
      marrow (remission-HPC), and normal HPC from their HLA-identical sibling bone
      marrow donor (donor-HPC). Specific lysis by CD8+ CTL clones was observed not only
      of the leukemic-HPC but also of the donor-HPC in 3/4 patient/donor combinations
      expressing mH antigen HA-1, 3/5 combinations expressing mH antigen HA-2, 2/3
      combinations expressing mH antigen HA-3, and 2/2 combinations expressing mH
      antigen HY-A1. In four patient/donor combinations the recognition of the donor
      HPC was clearly less than of the leukemic-HPC, indicating differential
      susceptibility to lysis by these mH CTL clones. In addition, differential
      recognition of leukemic-HPC and remission-HPC within seven patients was analyzed.
      In one patient expressing the HA-2 antigen on the leukemic cells the recognition
      of the remission-HPC was clearly less than of the leukemic-HPC. One CD4+ CTL
      clone showed specific lysis of the leukemic-HPC from an AML patient and a CML
      patient as well as of normal remission-HPC and donor-HPC. These results
      illustrate that in general CD8+ and CD4+ mH antigen specific CTL clones do not
      differentially recognize leukemic-HPC and normal-HPC. However, differences in
      susceptibility to lysis of malignant versus normal cells may contribute to a
      differential GVL effect.

PMID- 7635983
TI  - Role of interleukin-1 in the pathogenesis of experimental shigellosis.
AB  - The effect of human recombinant interleukin-1 receptor antagonist on intestinal
      inflammation, tissue destruction, and bacterial invasion during experimental
      shigellosis caused by Shigella flexneri was studied in the rabbit-ligated loop
      infection model. Intravenous infusion of the inhibitor at a dose of 2 mg/kg per
      h, was initiated 30 min before intestinal loops were ligated and infected, and
      continued during the 8-h period of infection. The animals treated with IL-1
      receptor antagonist showed a striking decrease in inflammation, destruction, and
      bacterial invasion of their tissues, both at the level of the villous intestine
      and Peyer's patches. This is conclusive evidence that interleukin-1 plays a
      critical role in the pathogenesis of shigellosis. This proinflammatory cytokine
      is here proposed as a major trigger of the inflammatory reaction which is
      characteristic of this invasive disease of the intestine, due to the particular
      interaction existing between S. flexneri and macrophages.

PMID- 7635984
TI  - Thyroid hormone-regulated brain mitochondrial genes revealed by differential cDNA
      cloning.
AB  - Thyroid hormone (T3) plays a critical role in the development of the central
      nervous system and its deficiency during the early neonatal period results in
      severe brain damage. However the mechanisms involved and the genes specifically
      regulated by T3 during brain development are largely unknown. By using a
      subtractive hybridization technique we have isolated a number of cDNAs that
      represented mitochondrial genes (12S and 16S rRNAs and cytochrome c oxidase
      subunit III). The steady state level of all three RNAs was reduced in hypothyroid
      animals during the postnatal period and T3 administration restored control
      levels. During fetal life the level of 16S rRNA was decreased in the brain of
      hypothyroid animals, suggesting a prenatal effect of thyroid hormone on brain
      development. Since T3 does not affect the amount of mitochondrial DNA, the
      results suggest that the effect of T3 is at transcriptional and/or
      postranscriptional level. In addition, the transcript levels for two nuclear
      encoded mitochondrial cytochrome c oxidase subunits: subunits IV and VIc were
      also decreased in the brains of hypothyroid animals. Hypothyroidism-induced
      changes in mitochondrial RNAs were followed by a concomitant 40% decrease in
      cytochrome c oxidase activity. This study shows that T3 is an important regulator
      of mitochondrial function in the neonatal brain and, more importantly, provides a
      molecular basis for the specific action of this hormone in the developing brain.

PMID- 7635985
TI  - Interleukin 4 activates a signal transducer and activator of transcription (Stat)
      protein which interacts with an interferon-gamma activation site-like sequence
      upstream of the I epsilon exon in a human B cell line. Evidence for the
      involvement of Janus kinase 3 and interleukin-4 Stat.
AB  - Germ line C transcripts can be induced by IL-4 in the human B cell line, BL-2.
      Utilizing a IFN-gamma activation site-like DNA sequence element located upstream
      of the I epsilon exon, we demonstrated by gel mobility shift assays that IL-4
      induced a binding activity in the cytosol and nucleus of BL-2 cells. This factor
      was designated IL-4 NAF (IL-4-induced nuclear-activating factors) and was
      identified as a tyrosine phosphoprotein, which translocates from the cytosol to
      the nucleus upon IL-4 treatment. Because these are the characteristics of a
      signal transducer and activator of transcription (Stat) protein, we determined
      whether antibodies to Stat proteins will interfere with gel mobility shift and
      found that antibodies to IL-4 Stat, also known as Stat6, but not antibodies to
      other Stat proteins, interfere with the formation of the IL-4 NAF complex.
      Congruous with the involvement of a Stat protein, IL-4 induced robust Janus
      kinase 3 (JAK3) activity in BL-2 cells. Cotransfection of JAK3 with IL-4 Stat
      into COS-7 cells produced an intracellular activity which bound the same IFN
      gamma activation site-like sequence and comigrated with IL-4 NAF in
      electrophoretic mobility shift assay. These results show that IL-4 NAF is IL-4
      Stat, which is activated by JAK3 in response to IL-4 receptor engagement.

PMID- 7635986
TI  - Tumor necrosis factor-alpha modulates monocyte/macrophage apoprotein E gene
      expression.
AB  - apo E has been shown to modulate cholesterol balance in arterial wall cells.
      Production of apo E by macrophages in atherosclerotic plaques could thereby
      influence the development of the plaque lesion. Cytokines, including TNF alpha,
      have been identified in human lesions, therefore, we undertook a series of
      studies to evaluate the effect of TNF alpha on monocyte/macrophage apo E
      production. The addition of TNF alpha to freshly isolated human monocytes led to
      a four- to fivefold increase of apo E mRNA abundance. The addition of TNF alpha
      to fully differentiated macrophages either had no effect or modestly inhibited
      apo E mRNA expression. THP1 human monocytic cells also responded to TNF alpha in
      a phenotype-specific manner. Treatment of these cells with TNF alpha produced a
      dose- and time-dependent increase in apo E mRNA. This increase was reflected in
      apo E synthesis and was associated with inhibition of DNA synthesis, and with
      induction of c-fos and ICAM-1 gene expression. Cell-permanent analogues of
      ceramide did not reproduce TNF alpha effect on apo E, but antagonists of protein
      kinase C did inhibit its effect. TNF alpha induction of apo E mRNA abundance was
      associated with stimulation of apo E promoter-dependent gene transcription. In
      summary, TNF alpha stimulates apo E gene transcription, mRNA abundance, and
      protein synthesis in the monocyte/macrophage in a phenotype-specific manner. Such
      regulation could significantly modify the amount of apo E present in vessel wall
      lesions.

PMID- 7635987
TI  - Transcriptional induction of prostaglandin G/H synthase-2 by basic fibroblast
      growth factor.
AB  - In serum-free mouse osteoblastic MC3T3-E1 cells, basic fibroblastic growth factor
      (bFGF) induced mRNA and protein for prostaglandin G/H synthase-2 (PGHS-2), the
      major enzyme in arachidonic acid (AA) conversion to prostaglandins. mRNA
      accumulation peaked at 1 h with bFGF 1 nM. In cells stably transfected with a 371
      bp PGHS-2 promoter-luciferase reporter, bFGF stimulated luciferase activity,
      which peaked at 2-3 h with bFGF 1-10 nM. In the presence of exogenous AA, bFGF
      stimulated PGE2 production, which paralleled luciferase activity. In serum-free
      neonatal mouse calvarial cultures, bFGF stimulated PGE2 production in the absence
      of exogenous AA. bFGF stimulated PGHS-2 mRNA accumulation, which peaked at 2-4 h
      and then decreased; there were later mRNA elevations at 48 and 96 h that were
      inhibited by indomethacin. In both MC3T3-E1 cells and neonatal calvariae, bFGF
      produced smaller and slower increases in PGHS-1 mRNA levels than for PGHS-2. bFGF
      stimulated bone resorption in mouse calvariae with a maximal increase of 80% at 1
      nM. Stimulation was partially inhibited by nonsteroidal anti-inflammatory drugs.
      We conclude that bFGF rapidly stimulates PGE2 production in osteoblasts, largely
      through transcriptional regulation of PGHS-2, and that prostaglandins mediate
      some of bFGF's effects on bone resorption.

PMID- 7635991
TI  - In memoriam the life of Milton Greenblatt.

PMID- 7635992
TI  - Psychopharmacologic agents and cancer: a progress report.

PMID- 7635989
TI  - Rabbit model of Lyme borreliosis: erythema migrans, infection-derived immunity,
      and identification of Borrelia burgdorferi proteins associated with virulence and
      protective immunity.
AB  - Erythema migrans (EM), persistent skin infection, and visceral dissemination can
      be induced reproducibly in the adult male New Zealand White rabbit by intradermal
      injection of as few as 10(3) Borrelia burgdorferi. EM was found to persist for 7
      +/- 3 d. Skin culture positivity (infection) cleared within a mean of 6.7 +/- 1.4
      wk after infection and similarly visceral infection was not demonstrated after 8
      wk; infection-derived immunity to intradermal challenge was evident 5 mo after
      initial infection. The extent of the protection against EM and dermal infection
      induced by untreated infection was directly related to the extent of prior in
      vitro passage of the B31 strain. Initial infection with as few as 4 x 10(3) B31
      passage 4 induced complete protection against EM and skin infection upon
      subsequent challenge with 4 x 10(7) B31, passage 4. Initial infection with B31
      passage 27 led to partial protection against EM along with complete protection
      against skin infection. Initial infection with passage 47 led to partial
      protection against EM, but conferred no protection against skin infection. Using
      serum from rabbits fully immune to reinfection, we defined a set of B.
      burgdorferi proteins present in virulent B31, but absent in the avirulent
      American Type Culture Collection B31 strain, termed "va" for virulent strain
      associated. The va proteins of B31 passages 1, 27, and 47 differed strikingly,
      thus raising the possibility that these changes may relate in a causal way to the
      differences in induction of protective immunity observed.

PMID- 7635990
TI  - Muscle-specific overexpression of lipoprotein lipase causes a severe myopathy
      characterized by proliferation of mitochondria and peroxisomes in transgenic
      mice.
AB  - In extrahepatic tissues lipoprotein lipase (LPL) hydrolyzes triglycerides thereby
      generating FFA for tissue uptake and metabolism. To study the effects of
      increased FFA uptake in muscle tissue, transgenic mouse lines were generated with
      a human LPL minigene driven by the promoter of the muscle creatine kinase gene.
      In these mice human LPL was expressed in skeletal muscle and cardiac muscle, but
      not in other tissues. In proportion to the level of LPL overexpression, decreased
      plasma triglyceride levels, elevated FFA uptake by muscle tissue, weight loss,
      and premature death were observed in three independent transgenic mouse lines.
      The animals developed a severe myopathy characterized by muscle fiber
      degeneration, fiber atrophy, glycogen storage, and extensive proliferation of
      mitochondria and peroxisomes. This degree of proliferation suggests that FFA play
      an important role in the biogenesis of these organelles. Our experiments indicate
      that LPL is rate limiting for the supply of muscle tissue with triglyceride
      derived FFA. Improper regulation of muscle LPL can lead to major pathological
      changes and may be important in the pathogenesis of some human myopathies. Muscle
      specific LPL transgenic mouse lines will serve as a useful animal model for the
      investigation of myopathies and the biogenesis of mitochondria and peroxisomes.

PMID- 7635993
TI  - Fluoxetine is ineffective for treatment of cocaine dependence or concurrent
      opiate and cocaine dependence: two placebo-controlled double-blind trials.
AB  - Cocaine dependence has proved difficult to treat, whether occurring alone or in
      combination with opiate dependence. No medication has been demonstrated to be
      uniquely effective. Fluoxetine was examined as a candidate in two randomized,
      double-blind, placebo-controlled trials, one with cocaine-dependent patients
      (study 1) and the other with patients both cocaine and opiate dependent (study
      2). It was selected for known specific action, antidepressant effects, minimum
      side effects, and data showing reduced cocaine effect and self-administration.
      Clinic visit frequency requirement, a variable with implications for treatment
      and cost, was also examined in study 1. A total of 228 patients in study 1 and 21
      patients in study 2 completed consent and intake procedures. Patients with
      serious medical or DSM-III-R diagnoses other than cocaine dependence (study 1) or
      opiate and cocaine dependence (study 2) were excluded. Study 1 patients were
      assigned to one of two visit frequency schedules (2 or 5 days/week) and one of
      three medication doses (0, 20, or 40 mg of fluoxetine/day). Study 2 patients
      received placebo or 20 mg of fluoxetine and 65 to 80 mg of methadone and attended
      the clinic 5 days/week. All patients participated in individual therapy sessions.
      Urine screens were conducted twice weekly. A fluoxetine dose response
      relationship emerged in study 1 for retention with groups from best to worst
      being placebo, 20 mg, and 40 mg. Dose effect order was the same for both visit
      conditions. Cocaine use persisted in all groups. The two visits/week condition
      was correlated with better retention than the five visits/week condition. A
      significant interaction emerged between intake urine and visit frequency;
      patients with benzoylecognine screens at intake used cocaine significantly less
      in the 5 days/week condition, while exhibiting no reduction in the 2 days/week
      condition. Patients cocaine positive at intake were better retained with
      infrequent visits. In study 2, a transient reduction in benzoylecognine-positive
      drug screens emerged for the fluoxetine group. These complementary studies
      demonstrate that fluoxetine is ineffective in reducing cocaine use or craving.
      Study 1 also points to setting conditions modulating treatment outcome.

PMID- 7635988
TI  - Endothelial cell injury initiates glomerular sclerosis in the rat remnant kidney.
AB  - The development of progressive glomerulosclerosis in the renal ablation model has
      been ascribed to a number of humoral and hemodynamic events, including the
      peptide growth factor, transforming growth factor-beta 1 (TGF-beta 1). An
      important role has also been attributed to angiotensin II (AII), which, in
      addition to its hemodynamic effects, can stimulate transcription of TGF-beta 1.
      We postulated that increased glomerular production of AII, resulting from
      enhanced intrinsic angiotensinogen expression, stimulates local TGF-beta 1
      synthesis, activating glomerular matrix protein synthesis, and leads to
      sclerosis. Using in situ reverse transcription, the glomerular cell sites of
      alpha-1 (IV) collagen, fibronectin, laminin B1, angiotensinogen, and TGF-beta 1
      mRNA synthesis were determined at sequential periods following renal ablation.
      The early hypertrophic phase was associated with global, but transient, increases
      in the mRNA for alpha-1 (IV) collagen. No changes were noted for fibronectin, TGF
      beta 1, and angiotensinogen mRNAs. At 24 d after ablation, at which time
      sclerosis is not evident, endothelial cells, particularly in the dilated
      capillaries at the vascular pole, expressed angiotensinogen and TGF-beta 1 mRNAs,
      as well as fibronectin and laminin B1 RNA transcripts. By 74 d after ablation
      angiotensinogen and TGF-beta 1 mRNAs were widely distributed among endothelial
      and mesangial cells, and were particularly prominent in regions of evolving
      sclerosis. These same regions were also notable for enhanced expression of matrix
      protein mRNAs, particularly fibronectin. All receptor blockade inhibited
      angiotensinogen, TGF-beta 1, fibronectin, and laminin B1 mRNA expression by the
      endothelium. We conclude that, as a result of hemodynamic changes, injured or
      activated endothelium synthesizes angiotensinogen, triggering a cascade of TGF
      beta 1 and matrix protein gene expression with resultant development of the
      segmental glomerular sclerotic lesion.

PMID- 7635994
TI  - Interindividual variations of desmethylation and hydroxylation of amitriptyline
      in a Japanese psychiatric population.
AB  - We measured the concentrations in plasma of amitriptyline and its metabolites,
      nortriptyline and geometric isomers of 10-hydroxynortriptyline and 10
      hydroxyamitriptyline, in 73 Japanese psychiatric patients receiving amitriptyline
      hydrochloride (Tryptanol; Banyu Pharmaceutical Co. Ltd., Tokyo, Japan) by high
      performance liquid chromatography. Although there were large interindividual
      variations of total drug concentrations and concentrations of parent or
      intermediate metabolic compounds in plasma, significant positive correlations
      were observed between these drug concentrations and daily doses of amitriptyline
      hydrochloride (milligrams per kilogram of body weight). The metabolic ratios for
      both hydroxylation and desmethylation varied substantially with approximately 8-
      to 19-fold interindividual variations. Frequency distribution histograms and
      probit analyses of these parameters identified neither definite poor
      hydroxylators nor poor desmethylators of amitriptyline.

PMID- 7635995
TI  - A placebo-controlled evaluation of the effects of buspirone on smoking cessation:
      differences between high- and low-anxiety smokers.
AB  - One hundred one smokers were divided into high and low trait anxiety groups on
      the basis of a normalized score on the Profile of Mood States Anxiety/Tension
      Scale and were randomly assigned to receive buspirone or placebo in a double
      blind fashion. After a 1-week baseline, smokers were exposed to an 8-week drug
      and behavioral intervention involving buspirone or placebo (up to 60 mg/day) with
      concurrent group cognitive behavioral intervention. All smokers were to quit
      smoking on the target date, set at 4 weeks after the program began. Medication
      was provided for an additional 4 weeks after group treatment ended. The results
      showed that buspirone had a beneficial effect on smoking abstinence but only
      among smokers who were already relatively high in anxiety and only for as long as
      the drug was available. Moreover, when provided to smokers who were relatively
      low in anxiety, the drug appeared to interfere with abstinence, although these
      effects also reversed when the drug was withdrawn. These effects were associated
      with an attenuation of the expected rise in anxiety before the quit date and its
      actual reversal thereafter, but only in the buspirone high-anxiety group. One
      month abstinence averaged 88, 61, 60, and 89% for the buspirone high-anxiety,
      placebo high-anxiety, buspirone low-anxiety, and placebo low-anxiety groups,
      respectively. By 12 months, abstinence for the buspirone and placebo high- and
      low-anxiety groups fell to 12, 23, 41, and 36%, respectively. No differences were
      observed for measures of self-efficacy, symptoms of withdrawal, medication side
      effects, or compliance.

PMID- 7635996
TI  - Time-dependent sensitization to triazolam? An observation in three studies.
AB  - Evidence of time-dependent sensitization (TDS) to triazolam was observed in three
      separate clinical studies. Study 1 was conducted in 12 normal-weight and 12 obese
      men; an intravenous bolus dose of triazolam, 0.5 mg, was administered on two
      occasions. Study 2 was a balanced crossover of three 0.25-mg oral doses and one
      0.20-mg oral dose of triazolam in 11 men. Study 3 was a balanced crossover of one
      placebo, one 0.5-mg, and two 0.4-mg oral doses of triazolam. In all three
      studies, treatments were separated by 6 days and included serial blood sampling
      for characterization of pharmacokinetics. Psychomotor response was assessed with
      the Digit Symbol Substitution Test and the Continuous Performance Test (CPT).
      Sedation was rated by an observer. For each measure, an effect ratio was
      calculated as the area under the effect curve divided by the area under the
      triazolam concentration curve; this parameter relates the extent of response
      relative to drug concentration in plasma. Effect ratios increased progressively
      by week for CPT; the percentage increase ranged from 31.9% in the study 1 normal
      subjects (week 1 to week 2; p = 0.08) to 631% in study 2 (week 1 to week 4; p =
      0.0013). Similar increases were observed for other responses. Overall, the effect
      ratio data demonstrate increasing responsiveness per unit of triazolam
      concentration when triazolam was administered as a single dose at 1-week
      intervals. This observation was incidental to the original objectives of the
      studies. However, the data suggest that definitive studies to verify the
      occurrence of this phenomenon need to be conducted.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7635997
TI  - Pharmacokinetics and pharmacodynamics of triazolam after two intermittent doses
      in obese and normal-weight men.
AB  - This study was designed to determine whether differences in alpha-1 acid
      glycoprotein and free drug concentrations result in an altered response to
      triazolam. Twelve normal-weight and 12 obese adult male subjects received
      intravenous doses of triazolam, 0.5 mg, on two occasions separated by 1 week.
      There was a small difference in the alpha-1 acid glycoprotein concentrations
      between groups but no difference in free fraction of triazolam. There was a
      longer terminal half-life (t1/2 beta) in the obese subjects (3.16 +/- 0.87 vs.
      3.83 +/- 1.24, p = 0.0098). Overall, week 1 data revealed no difference in effect
      between normal and obese subjects. However, response data reveal a pattern of
      increased sensitivity with the second exposure to triazolam. For example, area
      under the effect curve (AUEC) on all tests was significantly greater in week 2
      for both groups of subjects. For a memory test and sedation from 0 to 12 hours,
      AUEC/free AUC ratios were significantly greater in week 2 for all subjects. The
      obese had a higher ratio on week 2 than on week 1 for all psychomotor tests and
      sedation (0 to 4.5 hours; p < 0.05). The results of modeling psychomotor
      impairment-concentration data pooled by group for each week continue the pattern:
      week 1 data are similar between the obese and normal-weight subjects. Although
      EC50 values are up to 15% lower in week 2 for the normal-weight subjects, EC50
      values are as much as 66% lower in week 2 for the obese, where a lower EC50
      indicates greater sensitivity. Logistic regression of the recognition data is
      consistent with these results.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7635998
TI  - Treatment of obsessive-compulsive symptoms in schizophrenic patients with
      clomipramine.
AB  - Recent studies show that obsessive-compulsive symptoms may occur in many patients
      with schizophrenia and may predict a poor prognosis. Pilot studies have shown
      that some schizophrenic patients may improve if a serotonin reuptake blocker is
      added to their neuroleptic. We have performed a pilot, double-blind, crossover
      study of clomipramine (CMI) or placebo, added to maintenance psychotropic
      medication. Six schizophrenic patients with obsessive-compulsive symptoms were
      studied in a double-blind CMI versus placebo crossover protocol. The patients met
      DSM-III-R criteria for chronic schizophrenia, experienced obsessive-compulsive
      symptoms, and had been previously stabilized on their psychiatric medication. The
      patients were rated at baseline and longitudinally through the study with the
      Positive and Negative Symptom Scale for Schizophrenia (PANSS) and the Yale Brown
      Obsessive-Compulsive Scale (YBOCS). An analysis of covariance was used to compare
      the drug versus placebo effect at the final visit with the baseline rating as a
      covariate. Ratings on both the YBOCS and the PANSS showed that patients improved
      significantly more on CMI than on placebo. No patients experienced an
      exacerbation of psychotic symptoms. Preliminary findings from this double-blind,
      crossover, pilot study of CMI and placebo, designed to assess the effect of CMI
      in the treatment of schizophrenic patients with obsessive symptoms, suggest that
      CMI is superior to placebo in the treatment of obsessions and compulsions and
      improves overall schizophrenic symptoms. Further studies with larger samples and
      longer follow-up period are necessary to confirm these preliminary findings.

PMID- 7635999
TI  - Polymorphic drug metabolism in schizophrenic patients with tardive dyskinesia.
AB  - The metabolism of many neuroleptics cosegregates catalyzed by the polymorphic
      cytochrome P450 CYP2D6. The population can be phenotyped into extensive
      metabolizers (EM) and poor metabolizers (PM) with respect to this enzyme's
      activity. PM are likely to achieve higher than average concentrations of
      neuroleptic drugs in plasma, with an increased risk of extrapyramidal side
      effects, possibly including tardive dyskinesia. Sixteen white schizophrenic
      patients who had developed tardive dyskinesia during long-term neuroleptic
      treatment were phenotyped with debrisoquine and genotyped by CYP2D6-specific DNA
      amplification and EcoRI restriction fragment length polymorphism analysis. Only 1
      (6%) of the 16 patients had a PM genotype, 8 (50%) were homozygous, and 7 (44%)
      were heterozygous EM. None had a CYP2D6 genotype indicative of ultrarapid
      debrisoquine hydroxylation capacity. The patients were also phenotyped with
      mephenytoin, a probe drug for another polymorphic cytochrome P450, CYP2C19. One
      patient was a PM of S-mephenytoin, which corresponds to the frequency found in
      healthy white volunteers. In conclusion, there was no overrepresentation of PM of
      debrisoquine or of S-mephenytoin among the 16 patients with neuroleptic-induced
      tardive dyskinesia. However, the PM of debrisoquine had the highest score on the
      Simpson-Angus Rating Scale and the second highest on the Abnormal Involuntary
      Movement Scale, despite a very low neuroleptic dose. Also, the debrisoquine MR
      correlated significantly with the SARS score (rs = 0.685, p < 0.05, N = 10),
      indicating a relationship between the degree of impaired CYP2D5 activity and the
      severity of extrapyramidal side effects during neuroleptic treatment.

PMID- 7636001
TI  - Zolpidem and sleepwalking.

PMID- 7636002
TI  - Tamoxifen-associated reduction in tricyclic antidepressant levels in blood.

PMID- 7636000
TI  - Effectiveness of pindolol with selected antidepressant drugs in the treatment of
      major depression.
AB  - On the basis of a previous report suggesting the effectiveness of the beta
      adrenoceptor/5-HT1A antagonist pindolol to accelerate the antidepressant effect
      of a selective serotonin reuptake inhibitor (SSRI) and to produce a therapeutic
      effect in drug-resistant depressed patients, these open studies were undertaken
      to further explore the safety and efficacy of this strategy. In a first study,
      nine untreated unipolar depressed patients were given the SSRI paroxetine (20
      mg/day) together with pindolol (2.5 mg thrice daily). One patient stopped taking
      pindolol because of increased irritability after 3 days. One week later, seven
      patients had their Hamilton Rating Scale for Depression Score decreased by more
      than 50%. In a second study, 19 drug-resistant unipolar depressed patients (9 on
      paroxetine, 5 on sertraline, 3 on fluoxetine, and 2 on moclobemide) were also
      given pindolol at the same regimen and were assessed weekly. Two patients (one on
      sertraline, one on moclobemide) stopped taking pindolol also because of increased
      irritability after 2 and 3 days, respectively. After 1 week of pindolol addition,
      10 patients had a more than 50% decrease of their depression score. By day 14,
      all of the patients had a score of 10 or less, with the exception of those on
      sertraline. Improvement was maintained in all patients for at least 28 days on
      this combination. The results of these studies indicate that pindolol is safe
      when used in combination with an SSRI or moclobemide. Given the positive results
      obtained in this second open trial in 28 patients, this treatment strategy should
      be tested under double-blind conditions to establish its efficacy.

PMID- 7636003
TI  - Developmental and biologic correlates of early neuroleptic response.

PMID- 7636004
TI  - I read a recent report suggesting a causal relationship between a dystonic
      reaction in a patient and her use of sumatriptan. Is this likely?

PMID- 7636006
TI  - A special issue honoring Alan Peters.

PMID- 7636007
TI  - A histochemical study of iron-positive cells in the developing rat brain.
AB  - The establishment of normal iron levels in the neonatal brain is critical for
      normal neurological development. Studies have shown that both iron uptake and
      iron concentration in the brain are relatively high during neonatal development.
      This histochemical study was undertaken to determine the pattern of iron
      development at the cellular level in the rat forebrain. Iron-stained cells were
      observed as early as postnatal day (PND) 3, which was the earliest time point
      examined. At PND 3, there were four major foci of iron-containing cells: the
      subventricular zone and three areas within the subcortical white matter. These
      latter foci are associated with myelinogenic regions. The blood vessels were
      prominently stained for iron throughout the brain. At PND 7, as in PND 3, the
      majority of the iron-containing cells were in white matter. However, there were
      also patches of iron staining located specifically in the layer IV of the
      somatosensory cortex. These cortical patches were no longer visible by PND 14. At
      PND 14, numerous iron-stained cells were dispersed throughout white matter
      regions and the tanycytes aligning the third ventricle were prominently stained.
      The blood vessel staining was less prominent than at earlier time periods. By PND
      28, the adult pattern of iron staining was emerging. Iron-stained cells were
      aligned in rows in white matter and had an apparent preference for a location
      near blood vessels. This clustering of iron-positive cells around blood vessels
      gave the white matter a "patchy" appearance. The pattern of development, cell
      distribution, and morphological appearance of the iron-stained cells are
      consistent with that reported for oligodendrocytes. That iron-positive cells in
      the neonate may be oligodendrocytes is consistent with the reports for iron
      staining in adult brains. The recent reports that oligodendrocytes are highly
      susceptible to oxidative damage would be consistent with the high iron levels
      found in these cells. These results indicate that oligodendrocytes play a major
      role in the development of iron homeostasis in the brain. The role of iron in
      oligodendrocytes may be associated with metabolic demands of myelinogenesis,
      including cholesterol and fatty acid synthesis. However, these cells may be a
      morphologically similar but functionally distinct subset of oligodendrocytes
      whose function is to regulate the availability of iron in the brain.

PMID- 7636008
TI  - Oligodendrocytes in female carriers of the jimpy gene make more myelin than
      normal oligodendrocytes.
AB  - The female carrier of the jimpy (jp) gene is a model system to study the
      plasticity of neuroglial cells and the mechanisms they use to compensate for a
      temporary deficit in myelin. Myelin in the female carriers is reduced 30-40%
      during the first postnatal month but is normal in adults. We hypothesized that
      the number of oligodendrocytes (OLs) in the female carriers is increased, based
      upon previous data showing OL proliferation is increased but the number of dying
      OLs is only slightly elevated in development. To test this hypothesis, antibodies
      to carbonic anhydrase (CA)II, an OL-specific marker, were used to quantify the
      number of OLs in the spinal cords of 1-month-old and adult female carriers.
      Contrary to expectations, the number of OLs is significantly reduced in the
      dorsal funiculus and grey matter by 21% in adult female carriers compared to
      controls. A reduction of lesser magnitude is present in the 1-month-old animals.
      Electron microscopic montages prepared from normal and carrier dorsal funiculus
      were used to count total numbers of glia. Ultrastructural quantification shows a
      similar reduction in the number of OLs and confirms the validity of the CAII
      immunostaining as a means to quantify OLs. These data show that there are 21%
      fewer OLs in the central nervous system (CNS) of adult female carriers but normal
      amounts of myelin. Presumably, some OLs in the carrier CNS are maintaining more
      myelin than their counterparts in normal CNS would. These findings demonstrate
      that (1) a reduction in number of OLs does not necessarily involve a reduction in
      the amount of myelin, and (2) OLs have considerable flexibility in the amount of
      myelin they can make.

PMID- 7636005
TI  - Canny cases. Case 5: the dextral dodder.

PMID- 7636009
TI  - Morphology of individual axons projecting from area V2 to MT in the macaque.
AB  - Efferent axons from area V2 to the middle temporal area (MT) were anterogradely
      labeled by Phaseolus vulgaris-leucoagglutinin (PHA-L) or biocytin and analyzed in
      serial reconstructions. Five of seven reconstructed axons had three arbors (each
      < or = 200 microns in diameter) in layers 3-4, separated by 200-600 microns. Two
      axons terminated in what was apparently a single focus in layers 3-4. Of 15
      additional single arbors analyzed, 12 were concentrated in layers 3-4, and
      measured 200-250 microns across at their widest point. Three of these arbors were
      more columnar in shape (about 400 microns in diameter), and extended from layer 4
      toward layer 1. This system differs in several features from MT-projecting axons
      originating from V1. Namely, V2 axons terminating in MT are thinner
      (approximately 1.0 microns vs. 3.0 microns), their terminal specializations are
      more delicate, and their arbors are concentrated in layer 4 and overlying layer
      3, with no collaterals to layer 6. These differences may reflect the distinctive
      neuronal populations giving rise to these two connectional systems (different
      sizes of pyramidal neurons in layer 3 of V2, and a mix of pyramidal and spiny
      stellate cells in area V1). Differences may have implications for timing factors;
      that is, impulses from V1, subserved by large-caliber axons, may arrive in MT
      coincidentally with indirect connections via V2 to MT. Another consideration may
      be the functional architecture of MT. Regularly spaced clusters of neurons have
      been described in MT which have similar directionality preferences. The
      interarbor spacing of cortical efferents is consistent with a columnar
      organization, but the laminar specificity may indicate recruitment of different
      combinations of postsynaptic populations by V1 or V2 terminations.

PMID- 7636010
TI  - A memoir in appreciation of Alan Peters on his sixty-fifth birthday.

PMID- 7636011
TI  - Spindle neurons of the human anterior cingulate cortex.
AB  - The human anterior cingulate cortex is distinguished by the presence of an
      unusual cell type, a large spindle neuron in layer Vb. This cell has been noted
      numerous times in the historical literature but has not been studied with modern
      neuroanatomic techniques. For instance, details regarding the neuronal class to
      which these cells belong and regarding their precise distribution along both
      ventrodorsal and anteroposterior axes of the cingulate gyrus are still lacking.
      In the present study, morphological features and the anatomic distribution of
      this cell type were studied using computer-assisted mapping and
      immunocytochemical techniques. Spindle neurons are restricted to the subfields of
      the anterior cingulate cortex (Brodmann's area 24), exhibiting a greater density
      in anterior portions of this area than in posterior portions, and tapering off in
      the transition zone between anterior and posterior cingulate cortex. Furthermore,
      a majority of the spindle cells at any level is located in subarea 24b on the
      gyral surface. Immunocytochemical analysis revealed that the neurofilament
      protein triple was present in a large percentage of these neurons and that they
      did not contain calcium-binding proteins. Injections of the carbocyanine dye DiI
      into the cingulum bundle revealed that these cells are projection neurons.
      Finally, spindle cells were consistently affected in Alzheimer's disease cases,
      with an overall loss of about 60%. Taken together, these observations indicate
      that the spindle cells of the human cingulate cortex represent a morphological
      subpopulation of pyramidal neurons whose restricted distribution may be
      associated with functionally distinct areas.

PMID- 7636012
TI  - Commissural fibers may guide cholinergic neuronal migration in developing rat
      cervical spinal cord.
AB  - The present investigation examines the role of intercellular relationships in the
      guidance of neuronal migration in embryonic rat cervical spinal cord. A "U
      shaped" group of cholinergic neurons, was first detected on embryonic days (E)
      15.5-16 surrounding the ventral proliferative zone. At these stages, no
      cholinergic cells were observed in the dorsal spinal cord, but by E17, many of
      the "U-shaped" group of cholinergic cells appeared to have translocated dorsally,
      to become the cholinergic dorsal horn cells seen in older animals. Between E16
      and E17, these choline acetyltransferase (ChAT)-immunoreactive cells displayed
      primitive processes oriented dorsoventrally, suggesting migration along that
      axis. Two early forming substrates present in embryonic spinal cord have been
      implicated in the guidance of other populations of migrating neurons: glial cells
      organized in radial arrays and commissural axons aligned along the dorsoventral
      axis. Involvement of the commissural fibers with cholinergic cell migration seems
      more likely because the fibers and the translocation pathway have similar
      orientations. In double-labeling immunocytochemical studies of E15.5-17 spinal
      cord, some immature ChAT-containing neurons were directly adjacent to commissural
      fibers, as identified by SNAP/TAG-1 immunoreactivity. The temporal and spatial
      coincidence of developing cholinergic neurons and commissural axons is consistent
      with the hypothesis that these neurons could use commissural fibers as migratory
      guides. In addition, conventional electron micrographs were examined to determine
      if immature neuronal profiles were physically apposed to commissural axons.
      Immature neurons with leading and trailing processes oriented dorsally and
      ventrally, respectively, were embedded within and aligned along bundles of
      commissural fibers or along other similarly oriented neurons. This direct
      apposition of immature cells to the surfaces of commissural axons and other
      bipolar neurons is consistent with the hypothesis that the "U-shaped" group of
      cholinergic neurons may use commissural axons and other cohort neurons for
      guidance during their dorsal migration.

PMID- 7636013
TI  - Electron microscopy of cell islands in layer II of the primate entorhinal cortex.
AB  - An electron microscopic analysis of cell islands in layer II of the entorhinal
      cortex from rhesus monkeys was made to determine the ultrastructural features of
      these unique neuronal clusters. The rostral, intermediate, and caudal divisions
      of the entorhinal cortex were selected for electron microscopic examination. In
      the rostral division, neurons were grouped together in prominent clusters, often
      with 10 or more contiguous somata. Somatic and dendrosomatic appositions were
      frequent, without intervening cellular processes or specialized junctions. Somata
      were relatively small, typically 10-15 microns in diameter, with oval or circular
      nuclei that were euchromatic and contained nucleoli. Small nuclear infoldings
      were commonly seen. A thin shell of perikaryal cytoplasm contained numerous
      organelles. Axosomatic synapses were infrequent, with a mean of only 1.0 synapse
      per neuron per thin section. The neuropil contained numerous synapses, and
      myelinated axons were seen infrequently. In the intermediate division, somatic
      appositions were rarely observed. Somata were relatively large, typically 15-20
      microns in diameter, and displayed a moderate amount of cytoplasm. Axosomatic
      synapses were relatively common, with a mean of 3.3 synapses per neuron per thin
      section. In the caudal division, neurons were typically grouped in clusters of
      two to three contiguous somata. Neurons were about 15 microns in diameter and
      displayed a moderate amount of cytoplasm. Axosomatic synapses were of moderate
      frequency, with a mean of 2.5 synapses per neuron per thin section. The neuropil
      in the caudal division displayed a relatively high frequency of myelinated axons.
      Our analysis of three regions of the entorhinal cortex revealed significant
      differences in the frequency of somatic appositions and axosomatic synapses, and
      in certain ultrastructural features of the somata and neuropil. These results
      showed that cell islands in layer II of the entorhinal cortex display regional
      morphologic differences. The paucity of symmetric axosomatic synapses in the
      rostral division may correlate with this region's vulnerability in certain
      diseases.

PMID- 7636015
TI  - Cellular distribution of iron, transferrin, and ferritin in the
      hypotransferrinemic (Hp) mouse brain.
AB  - Hypotransferrinemic (Hp) mice have a point mutation or small deletion in the
      transferrin (Tf) gene, resulting in defective splicing of precursor Tf mRNA. Hp
      animals produce < 1% of normal Tf levels and require supplemental serum or
      purified Tf for survival. Because of the lack of endogenous brain Tf, we examined
      regional and cellular distributions of iron and iron regulatory proteins (Tf and
      ferritin) in selected brain regions of Hp mice. The regional distribution of
      iron, Tf, and ferritin in Hp brain was similar to normal except for the pattern
      of iron staining in hippocampus. The cellular distribution of iron, ferritin, and
      Tf was similar between Hp and normal animals. The predominant cell type staining
      for Tf and iron was oligodendrocytes. Qualitative observations suggest that the
      number of cells staining for iron was similar between Hp and normal mice, whereas
      the number of Hp Tf-positive cells was reduced. Ferritin immunostaining was
      similar in both cases. However, ferritin-positive cells were predominantly
      astrocytes, an observation unique to mice among species studied previously.
      Western blot analysis revealed that Tf present in Hp brain was of exogenous
      origin (from supplemental injections). Presumably, Tf transports the iron found
      in Hp oligodendrocytes. These data demonstrate that, despite reduced endogenous
      Hp brain Tf, iron and plasma Tf migrate or are transported to the appropriate
      cells (oligodendrocytes), bringing into question the role of endogenous brain Tf
      in extracellular iron transport.

PMID- 7636014
TI  - Relationship of the time of origin and death of neurons in rat somatosensory
      cortex: barrel versus septal cortex and projection versus local circuit neurons.
AB  - The birth of a neuron initiates a series of ontogenetic events, e.g., neuronal
      migration and differentiation. The outcomes of these events are neurons that
      successfully integrate into the cortical circuitry and neurons that are
      unsuccessful and ultimately die. The present study determined whether there is a
      relationship between the generation and death of cortical neurons. The decrease
      in the density of postmigratory neurons (heavily labeled by a single injection of
      [3H]thymidine) during normal development was used as an index of neuronal death.
      The survival indices of neurons varied with their times of origin. Neurons born
      from gestational day (G) 15 to G18 had the highest rates of survival. In
      contrast, the earliest and latest generated neurons (i.e., those born on G12-G13
      and those born on G19-G21, respectively) had the lowest survival rates. The role
      of neuronal death in the formation of cortical patterns was determined by
      assessing the survival of neurons in the barrels and septa of somatosensory
      cortex. No differences in the survival index were determined for neurons in the C
      row barrels and adjacent septa with a particular time of origin. The survival
      rate of projection and local circuit neurons was determined with a double
      labeling technique. One label, [3H]thymidine, was used to determine the time of
      origin of the neurons. The second label was used to identify the chemical or
      hodological characteristics of a neuron; projection neurons were labeled either
      by retrograde transport of horseradish peroxidase or by glutamate
      immunohistochemistry, and local circuit neurons were immunohistochemically
      identified with an antibody directed against gamma-aminobutyric acid (GABA)
      antibody.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7636016
TI  - Postnatal maturation of GABA-immunoreactive neurons of rat medial prefrontal
      cortex.
AB  - A light microscopic immunocytochemical approach has been used to examine the
      distribution and maturation of gamma-aminobutyric acid- (GABA) containing cells
      in rat medial prefrontal cortex (mPFC) at progressive postnatal stages. Between
      P1 and P5, labeled cells in the cortical plate show less differentiated
      morphological characteristics when compared to cells in the deeper laminae. By
      P10, however, most labeled cells in superficial laminae show more differentiated
      characteristics with some having a distinctive multipolar appearance. Between P1
      and P5, there is a significant increase (50%) in the density of GABA-containing
      cells in the superficial laminae, while concurrently there is an overall
      decreases in the subjacent deeper laminae. As the cortex continues to expand,
      there is a corresponding decrease in the density of GABA-immunoreactive cells in
      the outer two-thirds of the cortical mantle until approximately P15, stabilizing
      at 20-25 cells/100,000 microns2 for all laminae. Between P1 and P15, there is
      also a significant increase (133%) in the average size of labeled cells, followed
      by a gradual decrease of 30% between P15 and P41. During P1-7, there is a marked
      increase in the density of labeled axosomatic terminals in both the superficial
      (200%) and deep laminae (116%). In the superficial layers, however, the density
      of labeled terminals again increases by 86% between P12 and P18. In general, the
      present findings are consistent with the idea that there is a progressive
      maturation of the intrinsic GABAergic system in rat mPFC in a classic "inside
      out" pattern, and this involves extensive postnatal changes occurring during the
      first 3 postnatal weeks.

PMID- 7636017
TI  - GABA and glycine in the central auditory system of the mustache bat: structural
      substrates for inhibitory neuronal organization.
AB  - The distribution and morphology of neurons and axonal endings (puncta)
      immunostained with antibodies to gamma-aminobutyric acid (GABA) and glycine (Gly)
      were analyzed in auditory brainstem, thalamic, and cortical centers in the
      mustache bat. The goals of the study were (1) to compare and contrast the
      location of GABAergic and glycinergic neurons and puncta, (2) to determine
      whether nuclei containing immunoreactive neurons likewise have a similar
      concentration of puncta, (3) to assess the uniformity of immunostaining within a
      nucleus and to consider regional differences that were related to or independent
      of cytoarchitecture, and (4) to compare the patterns recognized in this bat with
      those in other mammals. There are nine major conclusions. (1) Glycinergic
      immunostaining is most pronounced in the hindbrain. (2) In the forebrain, GABA
      alone is present. (3) Some nuclei have GABAergic or glycinergic neurons
      exclusively; a few have neither. (4) Although there is sometimes a close
      relationship between the relative number of immunopositive neurons and the
      density of the puncta, just as often there is no particular correlation between
      them; this reflects the fact that many GABAergic and glycinergic neurons project
      beyond their nucleus of origin. (5) Even nuclei devoid of or with few GABAergic
      or glycinergic neurons contain relatively abundant numbers of puncta; some
      neurons receive axosomatic terminals of each type. (6) In a few nuclei there are
      physiological subregions with specific local patterns of immunostaining. (7) The
      patterns of immunostaining resemble those in other mammals; the principal
      exceptions are in nuclei that, in the bat, are hypertrophied (such as those of
      the lateral lemniscus) and in the medial geniculate body. (8) Cellular
      colocalization of GABA and Gly is specific to only a few nuclei. (9) GABA and
      glutamic acid decarboxylase (GAD) immunostaining have virtually identical
      distributions in each nucleus. Several implications follow. First, the
      arrangements of GABA and Gly in the central auditory system represent all
      possible patterns, ranging from mutually exclusive to overlapping within a
      nucleus to convergence of both types of synaptic endings on single neurons.
      Second, although both transmitters are present in the hindbrain, glycine appears
      to be dominant, and it is often associated with circuitry in which precise
      temporal control of aspects of neuronal discharge is critical. Third, the
      auditory system, especially at or below the level of the midbrain, contains
      significant numbers of GABAergic or glycinergic projection neurons. The latter
      feature distinguishes it from the central visual and somatic sensory pathways.

PMID- 7636018
TI  - Multiple gonadotropin-releasing hormone (GnRH)-immunoreactive systems in the
      brain of the dwarf gourami, Colisa lalia: immunohistochemistry and
      radioimmunoassay.
AB  - The present study characterizes gonadotropin-releasing hormone (GnRH) neuronal
      groups that are located in several different brain regions by investigating GnRH
      molecular species and projection patterns in an anabantid fish, Colisa lalia.
      First, we examined the molecular species of GnRHs in extracts of the brain and
      the pituitary by reverse-phase high-performance liquid chromatography followed by
      radioimmunoassays. We found salmon GnRH (sGnRH), chicken GnRH-II (cGnRH-II), and
      an unfamiliar GnRH-like substance. Next, to examine the distribution of each GnRH
      molecule in different GnRH neuronal groups, we performed immunohistochemistry
      using four kinds of antisera and an antibody. Furthermore, we performed brain
      lesioning experiments of terminal nerve (TN) cells, the most conspicuous GnRH
      immunoreactive cells in Colisa lalia. Comparisons of immunoreactive structures
      between TN-lesioned fish and untreated fish elucidated the projection area of
      each neuronal group. Three major neuronal groups were observed. TN-GnRH cells,
      which are located in the transitional area between the olfactory bulb and the
      telencephalon, showed strong sGnRH and weaker cGnRH-II immunoreactivity. TN-GnRH
      cells projected to wide areas of the central nervous system from the olfactory
      bulb to the spinal cord. The second group, located in the preoptic area, showed
      only sGnRH immunoreactivity and projected only to the pituitary. The third one,
      located in the midbrain tegmentum, exhibited strong cGnRH-II and weaker sGnRH
      immunoreactivity. This cell group projected mainly to brain regions posterior to
      the hypothalamus and the spinal cord. These different projection patterns suggest
      functional differentiation of each GnRH neuronal group.

PMID- 7636019
TI  - Early postmitotic neurons transiently express TOAD-64, a neural specific protein.
AB  - To identify proteins involved in the early development of the mammalian cerebral
      cortex, we previously used two-dimensional gels to compare proteins synthesized
      at different stages in corticogenesis in the embryonic rat at embryonic day 14
      (E14), E17, and E21. During this period, the cortex develops from a
      morphologically homogeneous population of proliferative precursor cells into a
      complex structure containing a diverse array of terminally differentiated
      neurons. Several proteins are up-regulated coincident with the generation of
      postmitotic neurons. Here we describe the purification, partial amino acid
      sequencing, and characterization of one of these proteins, TOAD-64 (Turned On
      After Division; 64 kDa), using polyclonal antisera to two synthetic peptides from
      the protein. This analysis reveals that TOAD-64 is a 64,000 Da protein that
      increases in abundance over the period of corticogenesis and then subsequently
      decreases to very low levels in the adult. The protein is neural specific and is
      expressed by postmitotic neurons as they begin their migration out of the
      ventricular zone into the developing cortical plate. It is expressed in advance
      of most other neuronal proteins. Progenitor cells do not express TOAD-64.
      Therefore, this protein is a marker for postmitotic cells that have made a
      commitment to a neuronal phenotype. The extremely early expression, the relative
      abundance in newly born neurons, as well as the restriction in expression to the
      period of initial neuronal differentiation suggest that TOAD-64 may be a key
      structural protein for early neuronal function.

PMID- 7636020
TI  - Synaptic connectivity of local circuit neurons in laminae III and IV of hamster
      spinal cord.
AB  - The present study was undertaken to examine the morphological bases of local
      synaptic interactions between dorsal horn interneurons. Seven interneurons
      responding to innocuous mechanical stimuli were intracellularly recorded in
      lamina III/IV of an isolated preparation of hamster spinal cord with partially
      intact innervation from an excised patch of hairy skin. Axonal arborizations were
      stained with horseradish peroxidase (HRP) and examined with an electron
      microscope. Five cells had extensive synaptic terminations (375-1,785
      boutons/axon) with localized distributions (rostrocaudal distance, 425-1,251
      microns) overlapping the dendritic trees. Two cells gave rise to deep stem axons
      that bifurcated into rostrocaudal daughter branches with collaterals ventral to
      the parent cell bodies (79-661 boutons/axon). Axons of local interneurons were
      thinly myelinated and formed terminal and en passant enlargements (mean [+/-
      S.D.] diameter = 0.88 +/- 0.24 microns, n = 157) containing clear, round vesicles
      20-60 nm in diameter. Collateral branches of deep axon cells produced round,
      vesicle-containing boutons comparable in diameter (0.93 +/- 0.22 microns, n = 31)
      to local axon cells. Both types of interneurons formed asymmetric synaptic
      contacts with dendritic profiles, but not with cell bodies or axon terminals.
      Postsynaptic profiles contained sparse ribosomes and had a mean diameter of 1.0
      +/- 0.5 microns (n = 49), significantly smaller than a population of identified
      proximal dendrites (2.3 +/- 0.9 microns, n = 47). HRP-labeled boutons were rarely
      (5/45 or 11%) in synaptic contact with more than one profile. We conclude that
      lamina III/IV interneurons make axodendritic synapses predominantly with distal
      dendrites. Thus, terminations of deep dorsal horn interneurons appear to have a
      postsynaptic distribution overlapping with axodendritic contacts formed by
      several functional classes of cutaneous sensory fibers signaling innocuous
      mechanical stimuli. Such overlap suggests that local spinal networks selectively
      and strongly influence afferent signals at initial stages of somatosensory
      integration.

PMID- 7636021
TI  - Distribution and spatial geometry of dopamine interplexiform cells in the retina.
      II. External arborizations in the adult rat and monkey.
AB  - The morphology and distribution of dopaminergic interplexiform cells in adult rat
      and monkey retinas were analyzed to determine any correlation with the function
      of dopamine in the outer retinal layers. The retinas were processed as whole
      mounts for tyrosine hydroxylase immunohistochemistry. There was a network formed
      by the sclerally directed processes of interplexiform cells in the inner nuclear,
      outer plexiform, and outer nuclear layers running throughout the retina. Their
      density was higher in the superior retina than in the inferior retina of the rat
      and was especially high in the superior temporal quadrant. The external network
      in this quadrant was significantly less dense in the monkey than in the rat, as
      are the interplexiform cells. The somata of interplexiform and other dopaminergic
      cells were about the same size in both rats and monkeys. Computer-assisted
      reconstruction of external arborizations of individual cells showed that external
      processes lay very close to horizontal and photoreceptor cells and also to blood
      capillaries. Because they were long, thin, and highly varicose; branched at right
      angles; and often arose from an axon hillock, the external processes were
      identified as axons. Therefore, we define the dopaminergic interplexiform cells
      as multiaxonal neurons, with at least one outwardly directed axon that reaches
      the outer plexiform layer. The function of the network of external processes from
      the interplexiform dopaminergic cells is discussed in terms of modulating the
      release of dopamine to external layers.

PMID- 7636023
TI  - D1 and D2 dopamine receptor gene expression in the rat striatum: sensitive cRNA
      probes demonstrate prominent segregation of D1 and D2 mRNAs in distinct neuronal
      populations of the dorsal and ventral striatum.
AB  - The postsynaptic effects of dopamine in the striatum are mediated mainly by
      receptors encoded by D1, D2, and D3 dopamine receptor genes. The D1 and D2 genes
      are the most widely expressed in the caudate-putamen, the accumbens nucleus, and
      the olfactory tubercle. Several anatomical studies, including studies using in
      situ hybridization with oligonucleotide and cDNA probes, have suggested that D1
      and D2 receptors are segregated into distinct efferent neuronal populations of
      the striatum: D1 in substance P striatonigral neurons and D2 in enkephalin
      striatopallidal neurons. In contrast, on the basis of several in vivo and in
      vitro studies, other authors have suggested the existence of an extensive
      colocalization of D1 and D2 in the same striatal neurons. Our study was
      undertaken in order to analyze in detail the expression of the D1 and D2 receptor
      genes in the efferent striatal populations, with special reference to the various
      striatal areas, and to yield insights into the question about D1 and D2 mRNA
      localization in the striatum. We have, therefore, used highly sensitive
      digoxigenin- and 35S-labeled cRNA probes to address this question. The present
      results demonstrate that the D1 and D2 receptor mRNAs are segregated,
      respectively, in substance P and enkephalin neurons in the caudate-putamen and
      accumbens nucleus (shell and core) and in the olfactory tubercle (for their
      largest part). A very small percentage of neurons may coexpress both genes. These
      results confirm that the D1 and D2 receptor genes are expressed in distinct
      populations of striatal efferent neurons in the normal adult rat.

PMID- 7636022
TI  - Two modes of hair cell loss from the vestibular sensory epithelia of the guinea
      pig inner ear.
AB  - In the vestibular and auditory neurosensory epithelia of poikilothermic
      vertebrates and of birds, damaged sensory "hair" cells are often deleted by
      extrusion from the apical surface. In contrast, in the adult mammalian auditory
      epithelium (the organ of Corti), the bodies of damaged hair cells degenerate
      within the epithelium. To determine whether this apparent difference is species
      related or is associated with the differing structural organisation of the
      epithelia, hair cell deletion in the mammalian vestibular end-organs was
      examined. The structural organisation of these tissues is closer to that of the
      inner ear epithelia of lower vertebrates than to the organ of Corti. Hair cell
      loss was induced by chronic, systemic treatment of guinea pigs with the ototoxic
      aminoglycoside antibiotic gentamicin. The vestibular sensory epithelia were
      examined at various times after treatment via scanning electron microscopy, thin
      sectioning, and staining f-actin with fluorescently labelled phalloidin. Two
      distinct modes of hair cell loss were identified: 1) degeneration of hair cells
      within the epithelium, which often showed morphological features consistent with
      those described for apoptosis, and 2) extrusion of intact cells from the apical
      surface. Neither process caused the formation of obvious lesions through the
      epithelial surfaces. Expansion of adjacent supporting cells during hair cell
      deletion resulted in repair that appeared to preserve permeability barriers.
      There was also no evidence of inflammation accompanying hair cell removal. Thus,
      with both modes of hair cell loss, it appeared that deletion of hair cells was
      achieved without disruption of tissue architecture or integrity. This may be
      important for subsequent repair and regeneration processes to operate.

PMID- 7636024
TI  - Development of branchiomeric and lateral line nerves in the axolotl.
AB  - The differentiation of neural crest and ectodermal placodes was examined in the
      axolotl in order to clarify the contribution of these tissues to the formation of
      the sensory ganglia of the branchiomeric and lateral line cranial nerves in
      salamanders. The most rostral branchiomeric nerves, the profundal and trigeminal
      nerves, appear to arise solely from an ectodermal placode and from neural crest,
      respectively. The sensory ganglia of the more caudal branchiomeric nerves--the
      facial, glossopharyngeal, and vagal nerves--are formed by a medial component that
      differentiates from the dorsomedial surface of migrating bands of neural crest
      associated with each of the developing branchial arches and with one or more
      lateral components that arise from epibranchial placodes located immediately
      dorsal and caudal to each pharyngeal pouch. Neuroblasts destined to form these
      sensory ganglia begin to differentiate from the epibranchial placodes as early as
      stage 26, whereas neural crest-derived neuroblasts can be recognized by stage 30.
      Centrally directed neurites of both groups of neuroblasts enter the medulla by
      stage 34, and their peripherally directed neurites form recognizable rami by
      stage 35. Five cranial lateral line nerves, in addition to the octaval nerve, can
      be recognized in axolotls. Each of these nerves arises from a separate
      dorsolateral placode that initially gives rise to the neuroblasts of a sensory
      ganglion whose peripheral neurites innervate sensory receptors subsequently
      formed from each placode. The time course of the differentiation of these nerves
      and receptors is comparable to that of the branchiomeric nerves. The possible
      roles of rhombomeres and their associated regulatory genes and pharyngeal pouches
      in the induction and specification of neural crest and ectodermal placodes are
      explored.

PMID- 7636026
TI  - Immunohistochemical study of two phosphoinositide-linked metabotropic glutamate
      receptors (mGluR1 alpha and mGluR5) in the cat visual cortex before, during, and
      after the peak of the critical period for eye-specific connections.
AB  - The distribution of two phosphoinositide-linked metabotropic glutamate receptors
      (mGluR1 alpha and mGluR5) was studied immunohistochemically in area 17 before,
      during and after the peak of use-dependent modification of eye-specific
      connections. In the adult, mGluR1 alpha immunoreactivity is high in all layers
      except layer IV, where mGluR5 immunoreactivity is concentrated. This difference
      in distribution indicates different functions for these two receptor subtypes.
      The laminar pattern of mGluR1 alpha immunoreactivity is similar in all three
      ages, but the overall labeling intensity decreases after the peak (6 weeks of
      age) of the critical period. The laminar pattern of mGluR5 immunoreactivity
      changes with age. It is expressed in most layers at 2 days of age and is found
      mainly in layer IV in the adult. This laminar distribution and developmental
      pattern match the distribution and the development of the geniculocortical
      terminals. The change in mGluR1 alpha labeling intensity and mGluR5 laminar
      distribution over time is consistent with both of these mGluRs being involved in
      sensory-dependent plasticity for eye-specific connections in the visual cortex.

PMID- 7636027
TI  - Glial cell line-derived neurotrophic factor supports survival of injured midbrain
      dopaminergic neurons.
AB  - Glial cell-lined derived neurotrophic factor (GDNF) has been shown to promote
      survival of developing mesencephalic dopaminergic neurons in vitro. In order to
      determine if there is a positive effect of GDNF on injured adult midbrain
      dopaminergic neurons in situ, we have carried out experiments in which a single
      dose of GDNF was injected into the substantia nigra following a unilateral lesion
      of the nigrostriatal system. Rats were unilaterally lesioned by a single
      stereotaxic injection of 6-hydroxydopamine (6-OHDA; 9 micrograms/4 microliters
      normal saline with 0.02% ascorbate) into the medial forebrain bundle and tested
      weekly for apomorphine-induced (0.05 mg/kg s.c.) contralateral rotation behavior.
      Rats that manifested > 300 turns/hour received a nigral injection of 100
      micrograms GDNF, or cytochrome C as a control, 4 weeks following the 6-OHDA
      lesion. Rotation behavior was quantified weekly for 5 weeks after GDNF. Rats were
      subsequently anesthetized, transcardially perfused, and processed for tyrosine
      hydroxylase immunohistochemistry. It was found that 100 micrograms GDNF decreased
      apomorphine-induced rotational behavior by more than 85%. Immunohistochemical
      studies revealed that tyrosine hydroxylase immunoreactivity was equally reduced
      in the striatum ipsilateral to the lesion in both cytochrome C and GDNF-injected
      animals. In contrast, large increments in tyrosine hydroxylase immunoreactivity
      were observed in the substantia nigra of animals treated with 100 micrograms of
      GDNF, with a significant increase in numbers of tyrosine hydroxylase
      immunoreactive cell bodies and neurites as well as a small increase in the cell
      body area of these neurons. The results suggest that GDNF can maintain the
      dopaminergic neuronal phenotype in a number of nigral neurons following a
      unilateral nigrostriatal lesion in the rat.

PMID- 7636025
TI  - Distribution of metabotropic glutamate receptor mGluR5 immunoreactivity in rat
      brain.
AB  - The receptor mGluR5 is a metabotropic glutamate receptor with messenger RNA
      abundantly present throughout cortex, hippocampus, and caudate/putamen that is
      also coupled to phosphatidyl inositide hydrolysis and calcium mobilization. In
      this study, the distribution of mGluR5 was examined in rat brain by
      immunocytochemistry. The antibody utilized is highly specific and does not cross
      react with the most closely related other metabotropic glutamate receptor, as
      determined by Western blot analysis of nonneuronal cells transfected with
      metabotropic receptor coding sequences. The receptor mGluR5 is widely expressed
      with the highest density in olfactory bulb, caudate/putamen, lateral septum,
      cortex, and hippocampus, as confirmed with both immunocytochemistry and Western
      blot analysis. Electron microscopic studies in hippocampus and cortex indicate
      that the labeling is mostly on membranes of dendritic spines and shafts. Light
      and electron microscopic evidence indicates that some mGluR5 immunoreactivity is
      located in presynaptic axon terminals, suggesting that mGluR5 may function as a
      presynaptic receptor.

PMID- 7636028
TI  - Spatial and temporal pattern of Purkinje cell degeneration in shaker mutant rats
      with hereditary cerebellar ataxia.
AB  - Temporal-spatial patterns of surviving Purkinje cells were studied quantitatively
      in a rat mutant (shaker) with differential hereditary cerebellar ataxia and
      Purkinje cell degeneration. Shaker rat mutants are characterized behaviorally as
      mild if they are ataxic or as strong if they have ataxia and tremor. Purkinje
      cells degenerate in both mild and strong shaker mutants, but the temporal and
      spatial patterns of cell death are strikingly different. In mild shaker mutants,
      Purkinje cell death is temporally restricted, with 31-46% of the Purkinje cells
      in lobules I-IX dying by 3 months of age. Very few Purkinje cells degenerate
      after this age. Purkinje cell death is spatially random. In lobules I-IX, every
      second, third, or fourth Purkinje cell degenerates. Purkinje cells in lobule X do
      not degenerate. In strong shaker mutants, Purkinje cell degeneration is
      temporally protracted and spatially restricted. By 3 months of age, most Purkinje
      cells in lobules I-VIa, -b, and -d have degenerated. Numerous Purkinje cells in
      the paravermis of lobules VIIb-VIII have also degenerated. Surviving Purkinje
      cells in the vermis and lateral hemisphere of lobules VIIb-VIII are aligned in
      parasagittally oriented stripes or transversely oriented bands. Purkinje cells
      continue to degenerate in localized areas of the posterior lobe such that, by 18
      months of age, surviving Purkinje cells are limited primarily to lobules VIc,
      VIIa, IXd, and X. Quantitative analysis indicates that none of the Purkinje cells
      in these lobules degenerate.

PMID- 7636029
TI  - Ipsilateral intracortical connections of physiologically defined cutaneous
      representations in areas 3b and 1 of macaque monkeys: projections in the vicinity
      of the central sulcus.
AB  - This study examined cortical connections of areas 3b and 1 in 17 macaque monkeys
      in reference to regional somatotopography. The fluorescent retrograde tracers
      Fast Blue and Diamidino Yellow and the anterograde tracer Rhodamine Dextran were
      injected into closely related cutaneously responsive sites in primary
      somatosensory cortex, e.g., adjacent digits. Supra- and infragranular layers in
      nearly all studied areas contained labeled pyramidal cells. Labeled infragranular
      cells predominated at the fringes of a distribution where cells labeled from
      different tracer injections in the same brain intermixed more. All topographical
      regions across area 1 have reciprocal connections with areas 4, 3a, 3b, 1, 2, and
      5. Intrinsic connections within area 1 and between it and area 2 are greatest;
      those with area 3b are less. Intrinsic connections within area 3b exceed all
      other nearby projections from this area which reciprocally connects with areas
      3a, 1 and 2. Connections appear topographically organized, including those with
      poorly mapped regions, like area 5. These connections link representations of
      neighboring skin and skip map regions that include disjoint dermatomal areas.
      Connections from adjacent digit representations overlap; however, double-labeled
      cells were not found. Distal and proximal digit zones mostly interconnect within
      an area. Intrinsic connections spread further in area 1 than in area 3b, thereby
      joining more disparate topographical zones than interareal connections, which
      project more homotopically. The domain over which the map in somatosensory
      cortical area I (SI) dynamically changes following intracortical microstimulation
      (Recanzone, Merzenich and Dinse, Cerebral Cortex 2:181-196, 1992) may depend on
      the range of intrinsic connections observed in this study. The extent of
      connections between cortical areas was less than expected and this challenges the
      hypothesis that these connections directly create receptive field enlargements.

PMID- 7636030
TI  - Cortical areas within the lateral sulcus connected to cutaneous representations
      in areas 3b and 1: a revised interpretation of the second somatosensory area in
      macaque monkeys.
AB  - Cortical connections between various body representations in areas 3b and 1 and
      lateral parietal cortex were examined in 18 macaque monkeys. We injected tracers
      (Fast Blue, Diamidino Yellow, Horseradish Peroxidase, and Rhodamine Dextran),
      alone or in combination, into closely related cutaneous responsive sites, e.g.,
      adjacent digits. Separated patches of labeling were found across the parietal
      operculum and insula for all injected locations. On the basis of
      cytoarchitectural criteria, the labeled regions include the second somatosensory
      area (SII), retroinsular area (Ri) and granular insula (Ig). Assuming the
      connections are homotopical from physiologically identified body representations
      in primary somatosensory cortex, the labeling patterns in SII include complete
      anterior and posterior body maps. The orientation of the body is erect in the
      posterior and supine in the anterior SII region. Area 3b has greater density of
      connections with anterior SII. The maps are mirror images aligned along the
      distal extremities. The anterior-posterior (A-P) length of the "SII region"
      exceeds 7 mm; it extends in the coronal plane from the fundus of the lateral
      sulcus to surface cortex near the anterior tip of the intraparietal sulcus. Two
      additional topographically organized maps are likely in Ri. These are "worm-like"
      body maps oriented along the A-P axis and joined at the head representation.
      Connections with the center of Ig are not somatotopically organized. The
      diversity of somatosensory areas in lateral parietal cortex revealed by the
      labeled connections was discussed in reference to prior mapping of SII in monkeys
      and was compared to reports of multiple areas in this region of cortex in other
      species.

PMID- 7636031
TI  - Somal size and location within the ganglia for electrophysiologically identified
      myenteric neurons of the guinea pig ileum.
AB  - The main goal of the present study was to examine the possibility of
      electrophysiologically identifying the excitable enteric S and AH neurons by use
      of one single criterion. Intracellular recordings were made from 189 cells of 64
      ganglia in isolated preparations of the myenteric plexus of the guinea pig distal
      ileum. The recordings were made under visual control of the cells by using
      Hoffman Modulation Contrast optics at high magnification (600x). From
      photomicrographs, the soma size and the location within the ganglion of the
      individual (unstained) cells were determined. The cells were classified into
      three types according to their electrical excitability and the shape of the
      action potential. Excitable cells were classified as AH cells (n = 84) if the
      action potential showed a shoulder on the falling phase, otherwise as S cells (n
      = 56). Cells in which no action potential could be evoked by current injection
      were classified as nonspiking (NS) cells (n = 49). The three classes of cells
      showed significant differences with respect to membrane potential, input
      resistance and fast synaptic input. The AH cells had significantly larger somata
      (P < 0.01) than the S cells. The NS cells were significantly smaller than the AH
      and S cells (P < 0.01). AH and S cells were found to be randomly located in the
      ganglia, whereas the NS cells clustered (P < 0.008) in close proximity to the
      onsets of internodal strands. We conclude that the shoulder of the action
      potential can be used as a single criterion to distinguish "on line" S and AH
      neurons unequivocally.

PMID- 7636032
TI  - Barreloids in adult rat thalamus: three-dimensional architecture and relationship
      to somatosensory cortical barrels.
AB  - Histochemical staining for cytochrome oxidase (CO) and axonal transport of
      horseradish peroxidase (HRP) were used to investigate thalamocortical connections
      in the vibrissa-barrel system of adult rats. CO staining revealed that the medial
      division of the ventrobasal thalamic nucleus (VBm) consists of intensely stained
      rod-like configurations, containing thalamocortical projection neurons and
      intervening neuropil, separated by lighter-stained septa. CO-dark rods span the
      thickness of VBm, are arranged in a pattern of rows and arcs that resembles the
      distribution of vibrissae on the mystacial pad, and are similar to the
      cytoarchitectonic structures termed "barreloids" in the mouse thalamus. Based
      upon the dimensions of CO-dark structures and the numerical density of neurons in
      VBm we estimated that a barreloid in the rat may contain 250-300 neurons. HRP
      injections into lamina IV of the somatosensory cortex led to retrograde labeling
      of neurons within one or more barreloids. When injections were centered within
      the CO-dark hollows of cortical barrels about 95% of retrogradely labeled neurons
      were located in the barreloid that is isomorphic to the injected barrel; up to 5%
      of labeled neurons were located within a single adjacent barreloid. Barrel hollow
      injections that also included a barrel side yielded a larger proportion of
      labeled neurons in non-isomorphic barreloids. Interestingly, such extra-barreloid
      labeling was topologically consistent in that HRP-labeled neurons were
      distributed among barreloids that corresponded to cortical barrels nearest the
      injected barrel side. Injections into the septa between barrels similarly
      resulted in labeling within barreloids that corresponded to cortical barrels
      flanking the septal injection site. Following lamina IV injections the density of
      labeled neurons tended to be highest in the ventrolateral one-half to two-thirds
      of VBm. Retrograde labeling of neurons in the dorsomedial one-third to one-half
      of VBm was more often observed after HRP injections at the lamina V/VI border.
      Thus, barreloid neurons may be heterogeneous with respect to their laminar
      pattern of terminations within the somatosensory cortex. Some HRP injections in
      the cortex resulted in orthograde labeling of corticothalamic axons in the
      barreloids. When observed, labeled corticothalamic axons arborized principally
      within the barreloid isomorphic to the injected barrel column. Indeed, terminal
      labeling was densest in the vicinity of neurons retrogradely labeled by the same
      injection.

PMID- 7636033
TI  - Prenatal development of rat primary afferent fibers: I. Peripheral projections.
AB  - Development of the peripheral innervation patterns of the L1-S1 lumbosacral
      ganglia and motor segments in embryonic day 12-17 (E12-17) rat embryos was
      examined using carbocyanine dyes. Individual dorsal root ganglia (DRGs) and/or
      isolated ventral horn (VH) segments, or individual peripheral nerves, were
      isolated in rat embryos fixed at different stages and filled with one of three
      carbocyanine dyes; DiI, DiA, and DiO. Individual experimental preparations
      included labeling of 1) single DRGs; 2) multiple DRGs with alternating dyes, DiO,
      DiI, and DiA; 3) single isolated VH segments; 4) multiple VH segments with
      alternating dyes; 5) single VH segments and the corresponding segmental DRGs with
      different dyes; and 6) two or more individual peripheral nerves labeled with
      different dyes. Results from these preparations have shown that the first fibers
      exited the lumbar ventral horn and DRGs at E12. At E13 major nerve trunks (e.g.,
      femoral and sciatic) were visible as they exited the plexus region. By E14
      afferent fibers were present in the epidermis of the proximal hindlimb, and the
      major nerve trunks extended into the leg. Fibers originating from L3 to L5 (DRG
      and VH) reached the paw by E14.5-E15, and the epidermis of the most distal toes
      was innervated by E16-E16.5. While afferent fibers and motor axons of the same
      segmental origin mixed extensively in the spinal nerve, fibers of different
      segmental origin combined in the plexus and major nerve trunks with little or no
      interfascicular mixing. Dermatomes observed at E14 were in general spotty and non
      contiguous. However, by E16 the dermatomes resembled mature forms with
      substantial overlap only between adjacent ones. Thus the adult pattern of spatial
      relationships between cutaneous afferent fibers in the periphery is established
      early in development.

PMID- 7636034
TI  - Prenatal development of rat primary afferent fibers: II. Central projections.
AB  - These studies were designed to determine the pattern of initial afferent fiber
      ingrowth into the prenatal spinal gray matter and the establishment of the
      topographic organization of the presynaptic neuropil in the dorsal horn. A total
      of 113 lumbar dorsal root ganglia were labeled with carbocyanine fluorescent dye
      DiI or DiA in 67 rat embryos and neonatal pups aged embryonic day 13 to postnatal
      day 0 (E13-P0). The initial fiber penetration of the lumbar spinal gray began at
      E15 and was restricted to the segments of entry. Subsequent growth of fibers into
      gray matter of adjacent segments began approximately one day later, and this
      delay was continued, about one day for each successive segment. A second wave of
      ingrowth of putative small-diameter afferents into the substantia gelatinosa
      began at E19 and also displayed the same rostrocaudal delay. Fiber ingrowth was
      specific and occupied the somatotopic area appropriate for the adult, from the
      earliest stages (E18) in which dorsal horn laminae could be adequately defined.
      The somatotopic organization of the presynaptic neuropil in laminae III and IV
      did not change significantly throughout embryonic development as the amount of
      overlap between adjacent and non-adjacent ganglion projections remained constant
      throughout embryonic development. In addition, it was found that fibers
      innervating the proximal and distal hindlimb entered the spinal gray
      simultaneously at E15 before the innervation of the distal toes was established.
      The results of these studies indicate that the somatotopic organization of the
      presynaptic neuropil is established very early in development and requires little
      refinement to match that seen in the adult. The simultaneous penetration of the
      fibers originating from the proximal and distal areas of the limb before
      innervation is complete suggests that this ingrowth may be independent of the
      establishment of specific peripheral connections.

PMID- 7636035
TI  - Chondroitin sulfate proteoglycans in the developing cerebral cortex: the
      distribution of neurocan distinguishes forming afferent and efferent axonal
      pathways.
AB  - The first thalamocortical axons to arrive in the developing cerebral cortex
      traverse a pathway that is separate from the adjacent intracortical pathway for
      early efferents, suggesting that different molecular signals guide their growth.
      We previously demonstrated that the intracortical pathway for thalamic axons is
      centered on the subplate (Bicknese et al. [1994] J. Neurosci. 14:3500-3510),
      which is rich in chondroitin sulfate proteoglycans (CSPGs; Sheppard et al. [1991]
      J. Neurosci. 11:3928-3942), whereas efferent axons cross the subplate to exit in
      a zone containing much less CSPG. To define the molecular composition of the
      subplate further, we used antibodies against CSPG core proteins and chondroitin
      sulfate disaccharides in an immunohistochemical analysis of their distribution in
      the developing neocortex of the rat. Immunolabeling for neurocan, a central
      nervous system-specific CSPG (Rauch et al. [1992] J. Biol. Chem. 267:19537
      19547), and for chondroitin 6-sulfate and unsulfated chondroitin becomes
      prominent in the subplate before the arrival of thalamic afferents.
      Immunolabeling is initially sparse in the cortical plate but appears later in
      maturing cortical layers. A postnatal decline in immunolabeling occurs uniformly
      for most proteoglycans, but, in the somatosensory cortex, labeling for neurocan,
      phosphacan, and chondroitin 4- and 6-sulfate declines in the centers of the
      whisker barrels before the walls. In contrast to neurocan, immunolabeling for
      other proteoglycans is either uniformly distributed (syndecan-1, N-syndecan, 5F3,
      phosphacan, chondroitin 4-sulfate), restricted to axons (PGM1), distributed
      exclusively on nonneuronal elements (2D6, NG2, and CD44), or undetectable
      (9.2.27, aggrecan, decorin). Thus, neurocan is a candidate molecule for
      delineating the intracortical pathway of thalamocortical axons and distinguishing
      it from that of cortical efferents.

PMID- 7636036
TI  - Transneuronal labeling of neurons in the adult rat brainstem and spinal cord
      after injection of pseudorabies virus into the urethra.
AB  - Transneuronal tracing techniques were used to identify sites in the central
      nervous system involved in the neural control of urethral function. The
      distribution of virus-infected neurons was examined in the spinal cord and
      brainstem at various intervals (56-96 hours) following pseudorabies virus (PRV)
      injection into the urethra. In the lumbosacral (L6-S1) spinal cord at 56 hours,
      neurons containing PRV immunoreactivity (PRV-IR) were located in the region of
      the sacral parasympathetic nucleus (SPN), around the central canal, and in the
      dorsal commissure. Some animals also exhibited PRV-IR in cells in the L6
      dorsolateral motor nucleus. At longer survival times (72-96 hours), PRV-IR cells
      were observed in the superficial and deeper laminae of the dorsal horn, and
      increased numbers of PRV-IR cells were consistently detected in the region of the
      SPN, around the central canal, and in the dorsal commissure. PRV-IR fiber-like
      staining also occurred along the lateral edge of the dorsal horn extending from
      Lissauer's tract to the region of the SPN. In rostral lumbar segments (L1-L2),
      PRV-IR cells were located in the region of the dorsal commissure and the
      intermediolateral cell nucleus (IML), around the central canal, and in the dorsal
      horn. After 72-84 hours, PRV-IR cells were also noted at more rostral levels of
      the neuraxis including the medulla, pons, midbrain, and diencephalon. At 72
      hours, PRV-IR cells were consistently observed in Barrington's nucleus (pontine
      micturition center), nucleus raphe magnus (RMg), parapyramidal reticular
      formation, and the A5 and A7 regions. At 78-84 hours, additional regions
      exhibited PRV-IR cells, including the periaqueductal gray, locus coeruleus, the
      dorsal and ventral subcoeruleus alpha, and the red nucleus. A few cells were also
      located in the lateral hypothalamic area. This distribution of PRV-labeled cells
      in the spinal cord and brainstem is similar in many respects to the distribution
      of cells labeled in previous studies by PRV injection into the urinary bladder.
      This overlap of urethra and bladder neurons is consistent with the results of
      physiological experiments indicating a close coordination between the central
      nervous control of bladder and urethral activity.

PMID- 7636037
TI  - The relationship between dental and medical education: a perspective for the
      1990s.

PMID- 7636038
TI  - Conference on the Future Direction of Dental Postgraduate Education. Rochester,
      New York, October 13-15, 1994. A tribute to Basil G. Bibby on his 90th birthday.

PMID- 7636039
TI  - Mentoring--a personal perspective.

PMID- 7636040
TI  - Status of postdoctoral dental education: clinical training.

PMID- 7636041
TI  - Research training: past, present, and future.

PMID- 7636042
TI  - Summary of panel discussion. 1--Is there a conflict between the postgraduate
      education of the clinician and the academic researcher?

PMID- 7636043
TI  - Some issues in problem-based learning.

PMID- 7636044
TI  - The role of mentorship in dental graduate education.

PMID- 7636045
TI  - A fifteen year perspective on dental school faculty.

PMID- 7636046
TI  - Summary of panel discussion: is traditional dental education in conflict with
      faculty development in the university setting?

PMID- 7636047
TI  - The oral physician... creating a new oral health professional for a new century.

PMID- 7636048
TI  - The impact of health care reform on postdoctoral dental education.

PMID- 7636049
TI  - Summary of panel discussion: what is the future of postgraduate dental education
      in light of projected political, social, and economic forces?

PMID- 7636050
TI  - Comparative efficacy and safety of a once-daily loratadine-pseudoephedrine
      combination versus its components alone and placebo in the management of seasonal
      allergic rhinitis.
AB  - BACKGROUND: The treatment of symptoms of seasonal allergic rhinitis often
      requires the use of a decongestant to improve nasal congestion, along with an
      antihistamine to adequately control other nasal, as well as nonnasal symptoms.
      METHODS: In this double-blind, placebo-controlled, multicenter study, 874
      patients with moderate to severe symptoms of seasonal allergic rhinitis were
      treated with one of the following: SCH 434 QD (a combination of 10 mg of
      loratadine in the coating and 240 mg of pseudoephedrine sulfate in an extended
      release core) once daily, 10 mg of loratadine once daily, 120 mg of
      pseudoephedrine sulfate every 12 hours, or placebo for 2 weeks. RESULTS: SCH 434
      QD was consistently superior to placebo in controlling the symptoms of seasonal
      allergic rhinitis. Composite symptom scores (total, total nasal, and total
      nonnasal) were reduced significantly in patients treated with SCH 434 QD as
      compared with placebo (p < 0.01). When compared with its individual components,
      reductions in mean symptom scores were consistently greater, numerically, in
      patients treated with SCH 434 QD than in patients who were treated with either
      loratadine or pseudoephedrine alone. SCH 434 QD was superior to pseudoephedrine
      in reducing nonnasal symptoms at all time points (p < 0.01), and superior to
      loratadine in relieving nasal stuffiness at end point (p < 0.01). In the
      physicians' evaluation of therapeutic response, the SCH 434 QD group had the
      greatest number of patients with a good or excellent response at end point (58%).
      All treatments were generally well tolerated with no serious or unusual adverse
      events. Insomnia and nervousness, adverse events commonly associated with
      pseudoephedrine, were noted in a significantly greater number of patients treated
      with SCH 434 QD or pseudoephedrine (p < or = 0.04) as compared with those treated
      with loratadine or placebo. CONCLUSIONS: The results of the study demonstrate
      that SCH 434 QD is more effective than placebo or either of its components alone
      in the treatment of seasonal allergic rhinitis.

PMID- 7636052
TI  - Bone mineral density and the risk of fracture in patients receiving long-term
      inhaled steroid therapy for asthma.
AB  - To determine whether high-dose or prolonged inhaled steroid therapy for asthma
      increases a patient's risk of osteoporosis and fracture, we measured bone density
      in 26 men and 43 women (41 postmenopausal, all of whom had received supplemental
      estrogen therapy) after treatment with an inhaled steroid for 10.1 +/- 5.5 years
      and oral prednisone for 10.7 +/- 9.7 years (mean +/- SD). Most had stopped
      receiving prednisone since commencing the inhaled steroid therapy. We found that
      bone densities (adjusted for age and sex to yield a z score) were lower in
      association with higher daily doses of inhaled steroid (p = 0.013 ANCOVA) and
      with the duration of past prednisone therapy (p = 0.032). Larger cumulative
      inhaled steroid doses were associated with higher bone densities (p = 0.002) and
      a reduction in the numbers of patients at risk of fracture. Bone density also
      increased with the amount of supplemental estrogen therapy (p = 0.058) and, at
      equivalent levels of inhaled and oral steroid use, women showed higher bone
      density z scores than did men. Women with a lifetime dose of inhaled steroid
      greater than 3 gm had normal bone density regardless of the amount of past or
      current prednisone use or the current dose of inhaled steroid. These data
      indicate that the daily dose, but not the duration, of inhaled steroid therapy
      may adversely affect bone density, and that estrogen therapy may offset this bone
      depleting effect in postmenopausal women.

PMID- 7636051
TI  - Inhibition of monocyte leukotriene B4 production after aspirin desensitization.
AB  - Aspirin-sensitive patients may be desensitized through a graded series of
      exposures to aspirin. We investigated the underlying mechanism of aspirin
      desensitization by measuring the release of leukotrienes B4 and C4 from calcium
      ionophore-stimulated peripheral blood monocytes. Compared with monocytes from
      normal volunteers (n = 5), monocytes from patients with aspirin-sensitive asthma
      (n = 10) released increased amounts of thromboxane B2 (1060 +/- 245 pg/ml vs 456
      +/- 62 pg/ml), leukotriene B4 (861 +/- 139 pg/ml vs 341 +/- 44 pg/ml), and
      leukotriene C4 (147 +/- 31 pg/ml vs 56 +/- 6 pg/ml) at baseline. After aspirin
      desensitization, thromboxane B2 release was almost completely suppressed in both
      groups. Leukotriene B4 release was significantly decreased in the aspirin
      sensitive group (484 +/- 85 pg/ml) but not in the normal subject group (466 +/-
      55 pg/ml). The need for prednisone decreased significantly after patients were
      desensitized to aspirin (10.4 +/- 2.2 mg/day to 1.6 +/- 2.8 mg/day). These
      results demonstrate that desensitization to aspirin results in decreased monocyte
      leukotriene B4 release. On the basis of the bronchospastic and inflammatory
      potential of leukotrienes, the decrease in leukotriene release may contribute to
      the clinical improvement seen after aspirin desensitization.

PMID- 7636053
TI  - Cross-reacting allergens in natural rubber latex and avocado.
AB  - BACKGROUND: An association between allergy to latex and avocado has been reported
      but the responsible cross-reacting allergens have not been identified or
      characterized. METHODS: Immunoblotting, immunoblot inhibition, and RAST
      inhibition methods were used to study cross-reactive proteins between natural
      rubber latex (NRL) and avocado. Sera from 18 patients with previously verified
      latex allergy were used as the source of IgE antibodies, and 11 of the patients
      underwent skin prick testing with fresh avocado. RESULTS: Fourteen of the 18 sera
      (78%) had IgE antibodies that bound to a total of 17 avocado proteins with
      apparent molecular weights ranging from 16 to 91 kd. Ten most strongly reacting
      sera were used for immunoblot inhibition studies. When NRL proteins were used as
      soluble inhibitors, binding of IgE antibodies to solid-phase avocado proteins was
      inhibited in a dose-dependent manner: 100 micrograms of NRL proteins inhibited
      IgE binding to 15 of the 17 avocado proteins, and 10 micrograms caused inhibition
      to 13 protein bands. Comparably, soluble avocado proteins were able to inhibit
      IgE binding to solid-phase NRL. Corresponding RAST inhibitions were performed
      with two patient sera; in both, avocado inhibited IgE binding to NRL and in one
      NRL proteins inhibited IgE binding to avocado. Skin prick test responses to fresh
      avocado were positive in seven of the 11 patients with latex allergy who were
      tested. CONCLUSIONS: The large number of inhibitable proteins in immunoblot
      experiments and clinical observations from skin prick tests suggest considerable
      immunologic cross-reactivity between NRL and avocado. The observed cross-reacting
      protein components may be responsible for the recently reported type I
      hypersensitivity reactions to NRL and avocado in patients with a preexisting
      allergy to either allergen.

PMID- 7636054
TI  - Comparison of the bronchodilatory effects of cetirizine, albuterol, and both
      together versus placebo in patients with mild-to-moderate asthma.
AB  - BACKGROUND: Many potential users of the H1 antihistamine cetirizine are asthmatic
      and may be using inhaled albuterol. This study was conducted to assess the
      possible bronchodilatory effect of cetirizine in patients with mild-to-moderate
      asthma and to determine whether cetirizine interacts with albuterol. METHODS: In
      a randomized, double-blind, placebo-controlled, crossover study, the effects on
      pulmonary function of 5, 10, and 20 mg oral doses of cetirizine with and without
      inhaled albuterol (180 micrograms) were determined in 12 patients at 11 time
      points over 8 hours. The primary measure of efficacy was forced expiratory volume
      in 1 second (FEV1). RESULTS: Cetirizine with or without albuterol significantly
      increased FEV1, peak expiratory flow rate, and forced expiratory flow rate
      between 25% and 75% of vital capacity relative to baseline and placebo but did
      not have a significant effect on forced vital capacity. The effect of 20 mg of
      cetirizine on FEV1 was generally greater than that of 10 or 5 mg, but the
      difference was statistically significant only at the 30-minute time point (p <
      0.05). All three cetirizine doses produced significantly greater increases than
      placebo in FEV1 and forced expiratory flow rate between 25% and 75% of vital
      capacity for 8 hours and in peak expiratory flow rate for 7 hours (p < 0.02).
      Albuterol alone had a significant effect on the four pulmonary function variables
      from 1 to 5 hours after baseline (p < 0.05), which is consistent with albuterol's
      recommended dosing frequency of every 4 to 6 hours. Albuterol alone increased
      FEV1 significantly more than 5 mg of cetirizine alone but not 10 mg or 20 mg of
      cetirizine alone at 60, 90, and 120 minutes after baseline, but all three doses
      of cetirizine increased FEV1 significantly more than albuterol 7 and 8 hours
      after baseline (p < 0.05), indicating that the bronchodilatory action of
      cetirizine lasts longer than that of albuterol. Cetirizine neither potentiated
      nor inhibited the bronchodilatory action of albuterol, but the two drugs appeared
      to have an additive bronchodilatory effect. None of the cetirizine treatments
      caused a worsening of pulmonary function, and all were well tolerated.
      CONCLUSIONS: Cetirizine has a significant bronchodilatory effect in patients with
      mild-to-moderate asthma and can be used to treat concomitant conditions (e.g.,
      allergic rhinitis) without concern that it will interfere with the
      bronchodilatory effect of albuterol or cause worsening of asthma by itself.

PMID- 7636055
TI  - Laboratory evaluation of a commercial immunoassay for fire ant allergen-specific
      IgE antibodies.
AB  - BACKGROUND: In vitro testing for fire ant sensitization would be useful for
      research purposes and in special clinical situations. METHODS: Laboratory
      performance of a commercial assay (Pharmacia CAP System, [PCS]), for specific IgE
      to Solenopsis invicta whole body extract was studied in 46 persons. Assay results
      were compared with those of venom skin testing, RAST, and ELISA. The
      manufacturer's global cutoffs were compared with cutoffs set by using methods
      derived from analytical detection limit theory. RESULTS: Thirty-two study
      subjects had positive skin test results, and 14 had negative results. Raw PCS
      data demonstrated a high level of correlation with RAST (rho = 0.941) and ELISA
      (rho = 0.931), and showed good correlation with skin testing (rho = -0.769).
      Analysis of binormal receiver operating characteristic curves, using skin test
      results as the reference standard, demonstrated no difference in performance
      among the three assays. The fixed global quantitative cutoff of 0.35 kUa/L was
      relatively insensitive. Use of the manufacturer's qualitative alternate scoring
      method cutoff substantially increased sensitivity without loss of specificity, as
      did lower limit of detection set by use of diluent. CONCLUSIONS: In situations in
      which skin testing for fire ant sensitization is not feasible, PCS appears to be
      an acceptable in vitro alternative method for determination of fire ant allergen
      specific IgE.

PMID- 7636056
TI  - Atopic allergy and delayed hypersensitivity in children with diabetes.
AB  - The prevalence of atopy was studied in 61 children with type I insulin-dependent
      diabetes mellitus (IDDM) and 72 age- and sex-matched control subjects. The two
      groups had a similar prevalence of atopic disease and did not differ
      significantly with respect to history, clinical findings, skin prick test
      results, total serum IgE levels, or presence of circulating IgE antibodies to
      allergen. We also studied delayed-type hypersensitivity reactions in 37 of the
      children with IDDM and 46 of the control subjects. Children with IDDM, as
      compared with those without IDDM, more often had other autoimmune diseases in
      their family histories (p < 0.01). They also had significantly stronger delayed
      hypersensitivity reactions than the control subjects, as determined with tetanus
      toxoid (p < 0.05) and mumps antigen (p < 0.01). The reactivity to purified
      protein derivate of tuberculin and Candida antigen was similar in the two groups.
      The study does not confirm previous suggestions of an inverse relationship
      between IDDM and atopic disease but does not confirm previous suggestions of an
      inverse relationship between IDDM and atopic disease but does confirm that IDDM
      is associated with other immunologic disturbances. The different genetic and
      immunologic traits do not prevent allergic manifestations in children with
      diabetes.

PMID- 7636057
TI  - Relationship between ultrasonically nebulized distilled water-induced
      bronchoconstriction and acetic acid-induced cough in asthmatic children.
AB  - BACKGROUND: Although wheezing and cough are the most common complaints in
      asthmatic persons, the mechanisms of hyperresponsiveness to bronchoconstriction
      and cough are nevertheless still unclear. OBJECTIVE: To investigate the common
      mechanisms between them, we studied the relationship between ultrasonically
      nebulized distilled water (UNDW) inhalation challenge and acetic acid (AA)
      inhalation challenge. In addition, we evaluated the effect of inhaled furosemide
      on both provocation tests by means of a placebo-controlled study. METHOD: In
      study 1 the UNDW, AA, and histamine inhalation challenges were performed in 40
      asthmatic children (26 boys, aged from 7 to 16 years; mean +/- SD, 11.2 +/- 2.0
      years). In study 2, 12 of the study 1 subjects (9 boys, 11.3 +/- 2.4 years) were
      subjected to each challenge test after inhalation of furosemide (10 mg/body
      square meters), or placebo (0.9% saline solution) on separate days. RESULTS:
      There was a good correlation between the provocative dose causing a 20% fall in
      forced expiratory volume in 1 second in the UNDW inhalation challenge (UNDW-PD20)
      and threshold dose causing cough in the AA inhalation challenge (R = 0.527; p <
      0.001). There was no relationship either between UNDW-PD20 and the provocative
      concentration causing a 20% fall in the histamine inhalation challenge (histamine
      PC20)(R = 0.384; p > 0.1), or between histamine-PC20 and the cough threshold (R =
      0.308; p > 0.05). In study 2 neither bronchoconstriction nor bronchodilation
      after inhalation of furosemide was observed. Inhaled furosemide exerted a
      protective effect on UNDW-PD20 and cough threshold of the AA inhalation challenge
      (p < 0.01 and p < 0.01, respectively), but did not attenuate histamine-PC20 (p >
      0.1). CONCLUSION: These data suggest that a common mechanism may cause
      hyperresponsiveness against both UNDW-induced bronchoconstriction and AA-induced
      cough in asthmatic children.

PMID- 7636058
TI  - A role for eosinophils in the pathogenesis of skin lesions in patients with food
      sensitive atopic dermatitis.
AB  - BACKGROUND: Atopic dermatitis is associated with skin and blood eosinophilia, but
      the role of eosinophils in the pathogenesis of the skin lesions is poorly
      understood. METHODS: To determine whether eosinophils play a role in the
      pathogenesis of the skin lesions in atopic dermatitis, we studied the
      relationship between the severity of the disease and both the number and the
      extent of activation of eosinophils in 15 patients with food-sensitive atopic
      dermatitis. Furthermore, this relationship was re-evaluated in eight of these
      patients who, after a period of elemental diet or total parenteral nutrition,
      showed significant clinical improvement. RESULTS: A clear relationship was found
      between the number of light-density eosinophils and the severity of the disease
      both during the active disease and after clinical improvement. Furthermore, we
      describe an adhesion-stimulating activity for eosinophils in patients' plasma,
      which does not change after recovery. CONCLUSIONS: Taken together, these
      observations strongly indicate that eosinophils play a pivotal role in the
      pathogenesis of the skin lesions in atopic dermatitis. In particular, the light
      density phenotype seems to be an essential feature of eosinophils involved in
      this process. The adhesion-promoting activity that we observed in the patients'
      plasma could be important in the recruitment of eosinophils from the blood into
      the skin.

PMID- 7636059
TI  - Inflammatory cell number and mediators in bronchoalveolar lavage fluid and
      peripheral blood in subjects with asthma with increased nocturnal airways
      narrowing.
AB  - BACKGROUND: Increased nocturnal airways narrowing (NAN) in asthma is thought to
      occur as the result of intensification of inflammatory processes in the airways.
      In this study we investigated the presence of inflammatory cells and mediators in
      bronchoalveolar lavage (BAL) fluid and peripheral blood (PB) and assessed their
      relationship with the occurrence of increased NAN. METHODS: BAL fluid and PB
      samples were assessed at 16:00 and 04:00 hours, separated by 7 days or more, in
      eight nonatopic healthy subjects (group 1) and 17 atopic subjects with asthma who
      were using inhaled bronchodilators only. The latter subjects were prospectively
      assigned to groups with and without NAN, as defined by a mean circadian peak
      expiratory flow variation of less than 15% (group 2) and 15% or more (group 3),
      respectively. RESULTS: Significantly higher eosinophil numbers and inflammatory
      activation products (eosinophil cationic protein, eosinophil-derived neurotoxin,
      histamine) were found in BAL fluid and PB from subjects with asthma in comparison
      with control subjects. However, increased NAN was not generally associated with a
      circadian fluctuation in cell number and inflammatory mediators in BAL fluid and
      PB. No differences in inflammatory cell numbers existed that distinguished
      between groups 2 and 3. However, in group 3 significantly higher BAL
      prostaglandin D2 levels (70 vs 24 pg/ml; range, 28 to 102 vs 11 to 90 pg/ml; p =
      0.04) and serum eosinophil cationic protein levels (17.6 vs 16.1 ng/ml; range,
      6.3 to 17.5 vs 6.3 to 60.3 ng/ml; p = 0.03) at 16:00 hours were detected compared
      with group 2. CONCLUSIONS: Our findings suggest that increased NAN is more likely
      to occur in subjects with asthma with ongoing increased cellular activation
      during the day.

PMID- 7636060
TI  - Identification and characterization of monocyte subpopulations from patients with
      bronchial asthma.
AB  - Monocytes are inflammatory cells that accumulate in the airway in asthma.
      Monocytes constitute a heterogenous cell population in normal subjects. The
      heterogeneity of monocytes from nine patients with mild asthma and nine normal
      subjects was studied by means of discontinuous density gradient centrifugation
      with use of bovine serum albumin. The rate of low-density monocytes recovered
      from patients with asthma was higher than that obtained from normal subjects. The
      functional activity of monocyte fractions from asthmatic and control subjects was
      assessed by using the release of interleukin-1 beta (IL-1 beta) and the intensity
      of lysosomal enzymes, such as acid phosphatase and nonspecific esterase. The low
      density cells produced less IL-1 beta than did cells of higher density in normal
      subjects. The IL-1 beta release was increased in low-density monocytes from
      subjects with asthma when compared with the same fraction from normal subjects (p
      < 0.01). The low-density monocytes had a higher activity of lysosomal enzymes
      than did cells of higher density in both asthmatic and normal subjects. Electron
      microscopic studies showed that low-density monocytes from the subjects with mild
      asthma appeared to have the morphologic characteristics of activated cells with
      more vacuoles in this periphery. This study shows that low-density monocytes from
      subjects with asthma retain the ability to be activated in vivo and in vitro and
      may orchestrate immune reactions in mild asthma.

PMID- 7636061
TI  - Shwachman-Diamond syndrome associated with hypogammaglobulinemia and growth
      hormone deficiency.
AB  - Shwachman-Diamond syndrome is a rare congenital disorder of unknown etiology.
      Characteristic abnormalities of this disease include pancreatic insufficiency,
      skeletal anomalies, growth retardation, recurrent infections, and hematologic
      abnormalities. Significant morbidity and mortality in these patients result from
      respiratory infections, which are not well explained on the basis of neutrophil
      defects. We have had the opportunity to perform an in-depth clinical immunologic
      and endocrinologic evaluation of a patient with this syndrome with recurrent
      respiratory tract infections. She was found to have profound humoral immunologic
      defects, and serum thymulin was absent. In addition, endocrinologic evaluation
      for growth retardation revealed growth hormone deficiency. The patient responded
      to treatment with supplemental growth hormone and intravenous gammaglobulin with
      accelerated growth and cessation of infections. This case is unique in that it
      links growth hormone deficiency and hypogammaglobulinemia in a non-X-linked
      manner and may provide the basis for treatment of other patients with this rare
      syndrome.

PMID- 7636062
TI  - Gold sodium thiomalate selectivity inhibits interleukin-5-mediated eosinophil
      survival.
AB  - Gold sodium thiomalate (GST) has been used for treatment of patients with
      bronchial asthma. In this study we investigated the effects of GST on interleukin
      (IL)-5-mediated eosinophil survival in vitro. Blood cells were obtained from
      patients with bronchial asthma (n = 18). Eosinophils were purified from the blood
      samples by a Percoll discontinuous method and negative selection of neutrophils.
      Eosinophils (10(6) cells/ml) were incubated for 96 hours in 10% fetal bovine
      serum-RPMI 1640 (Nissui Pharmaceutical Co. Ltd., Tokyo, Japan) with various
      concentrations of recombinant human IL-5 (2 x 10(-9) to 2 x 10(-5) mmol/L) and
      with GST (0.01 to 100 mumol/L) in 96-well, flat-bottomed microtiter plates at 37
      degrees C in a humidified 5% carbon dioxide atmosphere. Eosinophil viability was
      determined by trypan blue exclusion. IL-5 enhanced eosinophil survival in a dose
      dependent manner. Higher concentrations of GST inhibited IL-5-mediated eosinophil
      survival. Moreover, GST induced apoptosis of eosinophils by antagonizing the
      effects of IL-5. However, GST did not inhibit IL-3- or granulocyte-macrophage
      colony stimulating factor-mediated eosinophil survival, suggesting that GST
      selectivity inhibits IL-5-mediated eosinophil survival. These results suggest
      that IL-5-mediated eosinophil survival is inhibited by GST and that GST blocks
      eosinophil apoptosis by IL-5. It is possible that GST may be capable of
      controlling eosinophil functions regulated by IL-5 in patients with bronchial
      asthma.

PMID- 7636063
TI  - Allergy to green algae (Chlorella) among children.

PMID- 7636064
TI  - Hereditary angioedema with recurrent abdominal pain and ascites.

PMID- 7636065
TI  - Urinary eosinophil-derived neurotoxin in Churg-Strauss syndrome.

PMID- 7636066
TI  - Cervical lymphadenopathy as a sign of atopy in childhood.

PMID- 7636067
TI  - Sensitization (IgE antibody) to food allergens in wheezing infants and children.

PMID- 7636068
TI  - Allergy to cheese produced from sheep's and goat's milk but not to cheese
      produced from cow's milk.

PMID- 7636069
TI  - Oral allergy syndrome?

PMID- 7636070
TI  - Risk of sting anaphylaxis.

PMID- 7636071
TI  - Improper patient techniques with metered dose inhalers: clinical consequences and
      solutions to misuse.

PMID- 7636072
TI  - Drug delivery characteristics of metered-dose inhalers.

PMID- 7636073
TI  - Choosing the metered-dose inhaler spacer or holding chamber that matches the
      patient's need: evidence that the specific drug being delivered is an important
      consideration.

PMID- 7636074
TI  - What is optimum body weight?

PMID- 7636076
TI  - Computer-assisted instruction improves clinical reasoning skills of dietetics
      students.
AB  - OBJECTIVE: The effects of a computer-assisted instruction (CAI) tutorial program
      on learning clinical reasoning skills were compared in undergraduate dietetics
      students. DESIGN: A drill-and-practice program to control for time on task, and
      tutorial program, and a simulation program, as the test vehicle, were developed.
      The tutorial and simulation programs presented data on a patient with
      cardiovascular disease. SETTING: Subjects were tested in 30 undergraduate
      dietetics programs. SUBJECTS: Participants were 413 undergraduate diet therapy
      students enrolled in a coordinated program in dietetics (CPD) or a didactic
      program in dietetics (DPD). INTERVENTION: After completion of lectures on
      cardiovascular disease, subjects were given the drill-and-practice program plus a
      simulation test (group 1), the tutorial plus a simulation test (group 2), or the
      simulation test only (group 3). MAIN OUTCOME MEASURES: Scores on the simulation
      test were compared. Variables included type of CAI, dietetics program, year in
      school, computer experience, and experience using a medical chart. Mastery of
      objectives related to lower- and higher-level clinical reasoning skills
      introduced in the tutorial program was computed. STATISTICAL ANALYSIS: One-way
      analysis of variance and Student-Newman Keuls tests were conducted to determine
      any differences among the three groups. Reliability was determined using the
      Kuder-Richardson Formula 20. RESULTS: The reliability coefficient of the
      stimulation test was 0.93. Group 2 higher on the simulation test than group 1 or
      group 3. As a group, the CPD students scored higher than the DPD students. When
      CPD and DPD students were divided into the three experimental groups, there was
      no significant difference between the CPD and DPD student simulation scores.
      Group 2 mastered all objectives for lower-level reasoning skills and the higher
      level decision-making objective better than groups 1 and 3.
      APPLICATIONS/CONCLUSIONS: A computer tutorial program enhanced clinical reasoning
      skills in undergraduate dietetics students. This type of program could be used to
      supplement many topics taught in diet therapy and provide DPD students with
      experimental learning before their clinical intern practicums.

PMID- 7636075
TI  - Comparison of eight microcomputer dietary analysis programs with the USDA
      Nutrient Data Base for Standard Reference.
AB  - OBJECTIVE: To compare the general operating features and nutrient databases of
      eight microcomputer dietary analysis programs. DESIGN: A 3-day food record with
      73 food items was entered into each program by the authors. The general operating
      features of the program were summarized and evaluated. The nutrient database was
      evaluated by comparing the nutrient analysis output with the 1993 US Department
      of Agriculture (USDA) Nutrient Data Base for Standard Reference (NDB), full
      version, release 10, for microcomputers. RESULTS: The programs varied in cost,
      number of foods and nutrients in the database, use of non-USDA data, and
      inputting of data for missing values. We also found differences in the quality of
      user manuals and help screens, ease of food entry and averaging of 3-day nutrient
      intake, speed of analyzing and printing results, quality and number of
      print/export options, and overall ease of learning and using the program. All but
      one of the programs were within 15% of the USDA NDB for energy, protein, total
      fat, and total carbohydrates. However, there was some difference in the number of
      other nutrients and food components varying more than 15% from the USDA NDB.
      These differences occurred because of variations in the number of food items
      included in each programs' database and the number of missing nutrient values in
      the database. APPLICATIONS: Our results demonstrate the importance of carefully
      choosing a microcomputer dietary analysis program that is suitable to the user's
      specific and predetermined needs.

PMID- 7636077
TI  - Reading skills of dietetic interns and readability of dietetics literature.
AB  - OBJECTIVE: To assess and compare reading skills of dietetic interns with reading
      levels of internship references. DESIGN: A standardized reading test, the Nelson
      Denny Reading Test, measured reading skills of entering dietetic interns over 7
      years. A computerized readability program assessed the readability of references.
      SETTING: Dietetic internships in university and Veterans Affairs hospitals.
      SUBJECTS: Of 194 entering interns, 178 (92%) were included and 16 (89%) were
      omitted. MAIN OUTCOME MEASURES: Nelson-Denny percentile and grade equivalent
      scores for vocabulary, comprehension, and total. The Fog Index identified
      reference reading-grade levels. STATISTICAL ANALYSES PERFORMED: Descriptive
      statistics and analysis of variance. RESULTS: Interns from the two programs did
      not differ significantly on Nelson-Denny Reading Test scores or in application
      grade point average. Percentile means and standard deviations were 54.7 +/- 23.8
      for vocabulary, 51.2 +/- 25.0 for comprehension, 52.9 +/- 23.9 for total, and
      41.6 +/- 24.7 for reading rate. Nearly 20% (33 of 178) of interns read
      significantly below expected grade level. The fog Index assigned reference grade
      levels from 6.98 to 21.63 years. CONCLUSIONS: The majority of dietetic interns
      have strong reading skills and read within the references' reading levels. A
      minority may experience difficulties reading assignments. Preinternship reading
      skills assessment could lead to greater success in reading professional
      literature.

PMID- 7636078
TI  - Olfactory dysfunction and related nutritional risk in free-living, elderly women.
AB  - OBJECTIVE/DESIGN: To determine the nutritional risk associated with measured
      olfactory dysfunction in free-living, elderly women through analytic
      observational methods. Olfactory perception was measured orthonasally (odor:
      butanol threshold and odor identification) and retronasally (flavor: orange
      flavor threshold in sweetened gelatin). SETTING/SUBJECTS: Elderly women were
      recruited from New Haven, Conn, through posters and direct contact. Screening of
      120 elderly women identified 80 with high personal functioning to participate
      (mean age = 76 +/- 6 years, range = 65 to 93 years). All data were collected in
      subjects' homes. MAIN OUTCOME MEASURES: Nutritional risk was assessed in several
      ways: food behavior questionnaire; food preference questionnaire; interviews
      based on the National Cancer Institute food frequency questionnaire; five
      nonconsecutive, 24-hour food records; and weight, height, waist, and hip
      measurements. STATISTICAL ANALYSES: Correlation and regression analyses
      determined the separate association between olfactory perception and nutrition
      variables. RESULTS: Nearly half of the women (37 of 80) had olfactory
      dysfunction. The following nutritional risk pattern was associated with lower
      olfactory perception: lower interest in food-related activities (eg, enjoying
      cooking, eating a wide variety of foods); lower preference for foods with
      predominant sour/bitter taste (eg, citrus fruits) or pungency (eg, horseradish);
      higher intake of sweets; less intake of low-fat milk products; and nutrient
      intake profile indicative of higher risk for cardiac disease. APPLICATIONS:
      Olfactory dysfunction may make it more difficult for elderly women to maintain a
      diet to control risk for chronic disease. Practitioners should target nutrition
      intervention to elderly women with measured or self rated difficulty in
      preventing odors or olfactory flavor. Capitalizing on primary-taste quality and
      texture may help to compensate for the loss of olfactory flavor perception.

PMID- 7636079
TI  - Impact of meat consumption on nutritional quality and cardiovascular risk factors
      in young adults: the Bogalusa Heart Study.
AB  - OBJECTIVE: To document the contribution of meat consumption to the overall
      nutritional quality of the diet and assess its impact on cardiovascular risk
      factors in young adults. DESIGN AND SETTING: A cross-sectional survey of young
      adults in Bogalusa, La. SUBJECTS: We collected 24-hour dietary recalls from 504
      19- to 28-year-olds from 1988 through 1991. STATISTICAL ANALYSES: We examined
      dietary composition by meat consumption quartiles. Analysis of variance and
      Newman-Keuls range tests were performed. RESULTS: Young adults consume an average
      of 6.5 oz meat daily; whites most often consumed beef and blacks most often
      consumed pork and poultry. Persons in the < 25th percentile for meat consumption
      consumed a diet closest to recommended levels--with 11% of energy from protein,
      55% from carbohydrate, 32% from fat, 11% from saturated fatty acids, and 264 mg
      dietary cholesterol. In contrast, persons in the > 75th percentile for meat
      consumption consumed a diet with 18% of energy from protein, 40% from
      carbohydrate, 41% from fat, 13% from saturated fatty acids, and 372 mg dietary
      cholesterol. Intakes of heme iron and phosphorus were lower and calcium intake
      higher in persons in the < 25th percentile compared with those in the > 75th
      percentile for meat consumption. The percent of persons meeting two thirds of the
      Recommended Dietary Allowances for vitamin B-12, niacin, and zinc was greater in
      the > 75th percentile for meat consumption compared with the < 25th percentile
      for meat consumption. We noted no differences across meat consumption quartiles
      in blood lipids and lipoproteins, anthropometric measurements, and hemoglobin
      levels. APPLICATIONS/CONCLUSIONS: Consumption of moderate amounts of lean meat,
      along with healthier choices in other food groups, may be necessary to meet the
      current dietary recommendations.

PMID- 7636080
TI  - Comparisons of dietary intake and sources of fat in low- and high-fat diets of 18
      to 24-year-olds.
AB  - OBJECTIVE: To determine the sources of fat in the diets of 18- to 24-year-olds
      and to identify the food group choices of those consuming 30% of energy or less
      from fat. DESIGN: This study compared the fat intake, nutrient intake, and food
      group choices of young men and women consuming 30% or less or more than 30% of
      energy from fat. SUBJECTS: The 1989-1991 Continuing Survey of Food Intakes by
      individuals (CSFII) provided the study sample of 1,062 (436 men and 626 women) 18
      to 24-year-olds residing in the 48 coterminous states who completed one 24-hour
      food recall and two 1-day food records. MAIN OUTCOME MEASURES: Dietary fat,
      vitamin, mineral, and food group intakes were determined by analysis of the 24
      hour food recalls and the 1-day food records. STATISTICAL ANALYSIS PERFORMED:
      Tests were used to detect differences in nutrient and food group intakes between
      the two groups for both men and women. RESULTS: More than 75% of the sample
      consumed more than 30% of energy from fat. The men and women who consumed low-fat
      diets did so by choosing more low-fat dairy products, fruits, and grains. Men who
      consumed low-fat diets consumed significantly more alcohol than other men; women
      who consumed low-fat diets showed a similar trend although the difference was not
      statistically significant. Although men and women who consumed a high-fat diet
      did consume significantly greater amounts of fat and cholesterol, they also fared
      better in vitamin and mineral intake. CONCLUSIONS: A minority of young adults
      consumed 30% or less of energy from fat. Compared with those who consumed more
      than 30% of energy from fat, men consumed significantly greater mean amounts of
      vitamin C and folate, and women consumed significantly greater mean amounts of
      vitamin A and folate. Young adults who consumed more than 30% of energy from fat
      exceeded current recommendations for dietary fat intake; however, the men were
      less likely to be at risk for calcium deficiency and the women were less likely
      to be at risk for vitamin E and zinc deficiencies. Because excess dietary fat and
      alcohol can lead to chronic disease, dietitians should continue to educate people
      about the relationship between nutrition and health.

PMID- 7636081
TI  - Which diet for which renal failure: making sense of the options.
AB  - This review describes categories of renal function (normal, renal insufficiency,
      end-stage renal failure), types of treatment modalities (renal insufficiency
      management, dialysis, transplantation), and corresponding dietary parameters
      (protein, energy, fiber, sodium, fluid, potassium, phosphorus, calcium, vitamins,
      minerals). The focus is directed toward general and nonrenal specialty
      practitioners, who are encountering a growing number of geriatric patients and
      patients who have undergone renal transplantation or are in early renal failure.
      The findings indicate that early intervention may delay or prevent rapid
      progression of renal disease in some patients, that treatment modalities continue
      to need individualized dietary support to maintain nutritional status, and that
      transplant goals should include control of obesity and hyperlipidemia to reduce
      cardiovascular mortality.

PMID- 7636082
TI  - Academic measures available in sophomore year can predict application and
      admission to dietetic supervised practice programs.
AB  - The purpose of the study was to determine whether college grade point average
      (GPA) and application and admission to supervised practice programs could be
      predicted from measures available in the sophomore year. The sample consisted of
      193 graduates of a didactic program in a research university in class years 1986
      to 1993. Variables tested included GPA in required dietetics program courses, SAT
      scores, high school class rank, and age. prediction equations were developed
      using data from class years 1986 to 1992 and tested on subjects in class year
      1993. Subjects who applied to and were admitted to supervised practice programs
      had significantly higher GPAs. In class years 1986 to 1992, GPAs and SAT math
      scores of sophomores explained 88% of the variance in the college GPA, whereas
      the sophomore GPA for professional courses correctly classified 63% of applicants
      and 73% of admitted subjects. Using these prediction equations for the class of
      1993, college GPA of subjects was accurately predicted and 84% of applicants and
      75% of admitted subjects were correctly classified. The results of this study
      provide valuable information for didactic program directors to counsel students
      into or out of a dietetics program, and could decrease the number of graduates
      who do not complete registration requirements.

PMID- 7636083
TI  - Concept mapping: an effective instructional strategy for diet therapy.
AB  - Concept mapping is an instructional strategy that requires learners to identify,
      graphically display, and link key concepts in instructional reading material.
      Although proven effective in numerous disciplines as a means to promote critical
      thinking and self-directed learning, concept mapping has not been tested in diet
      therapy. The objective of this study was to implement concept mapping as a small
      group, cooperative learning strategy in an upper-division diet therapy course and
      to evaluate student attitudes about the effect of concept mapping on knowledge,
      self-directed learning, problem-solving, and collaborative skills. Students in
      the first semester (n = 27) initially learned course material by lecture (4
      weeks) followed by an integrated mapping/lecture format (12 weeks); the second
      semester (n = 25) used an integrated mapping lecture format for the full 16
      weeks. At the end of both semesters, students completed a 10-item original survey
      questionnaire. Responses for first (n = 25) and second (n = 21) semesters were
      analyzed independently. Results indicated that a majority of students thought
      participation in concept mapping enhanced knowledge of diet therapy principles (n
      = 19 of 25; 18 of 21), self-directed learning (n = 14 of 25; 18 of 21), critical
      thinking (n = 21 of 25; 14 of 21), problem-solving (n = 22 of 25; 16 of 21), and
      collaboration (n = 24 of 25; 20 of 21) skills. When noncooperation of teammates
      was a factor, concept mapping was viewed as more frustrating and time consuming
      than lecture. This study demonstrated concept mapping as an effective learning
      strategy for diet therapy; it improves students' ability to engage in self
      directed learning, critical thinking, collaboration, and creative problem
      solving. Results suggest that concept mapping is most effective when accompanied
      with comprehensive training, coordinated lectures, instructor guidance, and long
      term practice.

PMID- 7636084
TI  - Comparing counseling skills of dietetics students: a model for skill enhancement.

PMID- 7636085
TI  - Attitude of dietetics students and registered dietitians toward obesity.

PMID- 7636086
TI  - Nutrient intake of Mexican-American and non-Hispanic white women by reproductive
      status: results of two national studies.

PMID- 7636087
TI  - Dairy product intake of the oldest old.

PMID- 7636088
TI  - Trends in use of vitamin and mineral supplements in the United State: the 1987
      and 1992 National Health Interview Surveys.

PMID- 7636089
TI  - Dietetics education by distance: current endeavors in CAADE-accredited/approved
      programs.

PMID- 7636090
TI  - Associations of physical activity with performance-based and self-reported
      physical functioning in older men: the Honolulu Heart Program.
AB  - OBJECTIVE: To examine the association of self-reported physical activity with
      performance-based and self-reported physical functioning measured 3 to 5 years
      later. DESIGN: A population-based, longitudinal study. SETTING: The island of
      Oahu, Hawaii. PARTICIPANTS: Subjects were 3640 Japanese-American men older than
      70 years of age. MEASUREMENTS: Estimated daily energy expenditure evaluated from
      self-reported engagement in a variety of activities determined from a mail survey
      in 1988; physical functioning status determined from both self-report and
      performance-based measures 3 to 5 years later. The effect of physical activity on
      physical functioning scores was determined through multiple logistic regression
      and analysis of covariance techniques for subjects who had chronic diseases as
      well as those in a healthy subsample. RESULTS: For the healthy subsample, those
      who were highly active in 1988 were more likely to have optimal function for the
      basic activities of daily living score (odds ratio 2.3; confidence interval (CI)
      1.1 to 4.9), home management skills score (odds ratio 1.5; CI 1.1 to 2.1), and
      physical endurance-type tasks score (odds ratio 1.7; CI 1.2 to 2.4) than subjects
      classified as low active. A significant linear trend was found additionally
      across physical activity level for time to walk 10 feet and grip strength (P
      values < .001). Similar results were found for subjects with chronic diseases;
      however, most of the benefit of physical activity for this subsample occurred for
      subjects who were at least physically active at a moderate level. CONCLUSION:
      Engaging in physical activity is predictive of a high level of physical
      functioning in older men with and without chronic diseases. Participation in at
      least moderate physical activity may be sufficient to maintain optimal physical
      functioning in subjects afflicted with chronic diseases.

PMID- 7636091
TI  - Hematological and biochemical laboratory values in older Cardiovascular Health
      Study participants.
AB  - OBJECTIVE: To define reference hematologic and biochemical lab values in older
      individuals. DESIGN: Randomly selected, age- and gender-stratified participants.
      SETTING: Visits by participants to four research clinics. PATIENTS: A total of
      5201 participants in the Cardiovascular Health Study, an observational study of
      older Medicare-eligible individuals living at home. MEASUREMENT: Information
      about health status, previous illness, and medication use was obtained from
      participants and/or their MDs. This information was used to define a healthy
      subset of the population. Blood samples were obtained for Cholesterol, HDL and
      LDL cholesterol, fasting and 2-hour postload glucose and insulin, fibrinogen,
      factors VII and VIII, potassium, creatinine, albumin, uric acid, white blood
      count, hematocrit, hemoglobin, and platelet count. RESULTS: Significant
      differences were found for age group and/or gender for all mean values. Many
      tests were significantly different from the generally accepted reference ranges
      used in clinical laboratories. CONCLUSIONS: In some situations accepted
      laboratory norms for the general population can not be extrapolated to older
      adults. There are implications for both research and clinical practice.

PMID- 7636092
TI  - Occult caffeine as a source of sleep problems in an older population.
AB  - OBJECTIVE: To evaluate the impact of caffeine in medication on sleep complaints
      in a community population of persons aged 67 or older. DESIGN: Cross-sectional
      analysis. SETTING: Iowa 65+ Rural Health Study. PARTICIPANTS: Those who completed
      their own interview, including a section on the use of medications, during the
      third annual in-person follow-up in 1984-1985. MEASUREMENTS:  MAIN OUTCOMES:
      trouble falling asleep or other sleep complaints. Covariates: use of caffeine
      containing medication, spasmolytic, or sympathomimetic drug; number of drugs
      used; depressive symptoms; self-perceived health; comorbidity, hip fracture,
      arthritis, ulcer of stomach or intestines; and consumption of caffeinated
      beverages. RESULTS: The prevalence of caffeinated medication use by participants
      was 5.4%. Those reporting the use of any caffeine-containing medication were at
      an increased risk of having trouble falling asleep (Odds Ratio [OR] = 1.79, 95%
      confidence interval [CI] = 1.19-2.68). There was no significant risk of other
      reported nighttime or daytime sleep problems associated with use of caffeine
      containing drugs. Even after adjusting for other factors that could interfere
      with initiation of sleep, such as painful disease, depressive symptoms,
      polypharmacy, use of specific medications known to interfere with sleep, and
      coffee consumption, the use of caffeine-containing medication still presented a
      significantly increased risk of having trouble falling asleep (OR = 1.60, CI =
      1.04-2.46). Although those participants using over-the-counter analgesic
      medication containing caffeine had an increased risk of trouble falling asleep
      (OR = 1.88, CI = 1.22-2.90), there was no significant risk of trouble falling
      asleep for those who took similar noncaffeinated OTC analgesic drugs (OR = 1.26,
      CI = 0.87-1.83). CONCLUSIONS: The use of caffeine-containing medication is
      associated with sleep problems. Healthcare providers should be aware of potential
      problems associated with over-the-counter medications containing caffeine and
      should counsel patients about the potential of sleep problems. Older patients
      should be encouraged to read the label on medications and to select drugs that
      are caffeine-free when that is possible.

PMID- 7636093
TI  - Clean intermittent catheterization: safe, cost-effective bladder management for
      male residents of VA nursing homes.
AB  - OBJECTIVES: To compare the safety and cost of clean versus sterile intermittent
      bladder catheterization in male nursing home residents. To provide evidence to
      support the hypothesis that intermittent catheterization is a valid, alternative
      method of bladder management in male residents of long-term care in whom urinary
      retention is a documented problem. DESIGN: Randomized clinical trial. SETTING:
      Three long-term care sites having predominantly male populations. PARTICIPANTS:
      Eighty male veterans, residents of three long-term care facilities, ranging in
      age from 36 to 96 years with a mean age of 72. INTERVENTIONS: Standardized
      procedures for clean and sterile intermittent catheterization (IC) were
      implemented by staff nurses at each site. Patients were randomized into clean and
      sterile IC groups. Nursing time and catheterization equipment usage were recorded
      using bar code readers. Clinical data were collected from the medical chart.
      Treatment of urinary tract infection was prescribed by the medical personnel
      responsible for each individual resident. MEASUREMENTS: We compared the number of
      treatment episodes for symptomatic bacteriuria between groups randomized to
      receive either clean or sterile intermittent catheterization. Laboratory analysis
      of blood and urine was done on predetermined days. Control variables were
      research site and patient history of urinary tract infection within the last 6
      months. A cost comparison of nursing time and equipment usage for the two
      catheterization techniques was also performed. RESULTS: No significant
      differences were found between clean and sterile groups with regard to number of
      treatment episodes, time to first infection, type of organism cultured, or cost
      of antibiotic treatment. The cost of sterile technique was considerably higher
      both in terms of nursing time and supplies. CONCLUSIONS: Findings from this study
      demonstrate that clean technique intermittent catheterization is a safe and cost
      effective bladder management technique with male, nursing home residents, despite
      the frailty of this high risk population. An annual savings of approximately
      $1460 per patient in nursing time and catheterization supplies could be
      anticipated if a patient were catheterized an average of four times per day
      substituting clean IC technique for sterile IC technique.

PMID- 7636094
TI  - Incidence of injury-causing falls among older adults by place of residence: a
      population-based study.
AB  - OBJECTIVE: To describe the incidence and associated factors of injury-causing
      falls by place of residence. DESIGN: A prospective population-based study.
      SETTING: Five municipalities in northern Finland. PARTICIPANTS: All persons in
      the five communities aged 70 years or older living at home (n = 1016) and in long
      term institutionalized care (n = 143). MEASUREMENTS: We recorded all fall
      incidents during a 2-year period by occurrence and severity of injury, using
      diary reporting and regular calls and by examining the medical and nursing
      records of all participants. The times, places, circumstances, and medical
      treatment needed were recorded as well. RESULTS: Men living at home experienced
      71 minor injuries/1000 person years (PY), 42 major soft tissue injuries/1000PY,
      and 12 fractures/1000PY; women at home experienced 175 minor injuries/1000PY, 65
      major soft tissue injuries/1000PY, and 33 fractures/1000PY. Institutionalized
      older men had 272 minor injuries/1000PY, 122 major soft tissue injuries/1000PY,
      and 41 fractures/1000PY; institutionalized women had 292 minor injuries/1000PY,
      131 major soft tissue injuries/1000PY, and 58 fractures/1000PY. Falls causing
      injury to older adults in long-term institutionalized care were more evenly
      distributed by time of day than those that occurred at home. The majority of the
      injuries sustained in long-term institutionalized care were injuries to the head.
      The incidence rate of fall injuries requiring medical attention in women,
      113/1000PY, was twice that in men, 57/1000PY. CONCLUSIONS: Injury-causing falls
      are more frequent in older people living in long-term institutionalized care, and
      the time-distribution and some circumstances differ from those of injury-causing
      falls in home-dwelling older people.

PMID- 7636095
TI  - Developing a new metric for ADLs.
AB  - BACKGROUND: Most ADL summary measures add up the number of dependencies. They
      assume an equal weighting among items and require an arbitrary definition of
      dependency. METHODS: A panel of experts in geriatrics was asked to rate a set of
      ADL and IADL components in terms of the contribution of each to overall
      dependency using a magnitude estimation (ME) technique. The ratings were done for
      both domains and for levels of function within each domain. The resultant scores
      were compared with the usual dependency count approach. RESULTS: The distribution
      of weighted items appears to have face validity. The pattern of dependency traced
      by the ME model was intermediate between those created by simple counts with two
      different definitions of dependency. The ME approach has stronger statistical
      properties than the ordinal scoring approach. CONCLUSIONS: The ME approach
      appears to be a reasonable and workable method for creating a measure that
      permits meaningful statements about the mean value of functional dependencies.
      This result can be used for any comparison of means, such as across individuals,
      across aggregates of individuals, or across time.

PMID- 7636096
TI  - Do geriatric programs decrease long-term use of acute care beds?
AB  - OBJECTIVE: To determine whether the introduction of coordinated geriatric and
      discharge planning services at teaching and community hospitals in Toronto has
      changed the number of beds occupied by patients awaiting transfer to long-term
      care institutions. DESIGN: Retrospective review of social work records for the
      period 1985-1992. SETTING: Two tertiary and four primary acute care hospitals in
      Metropolitan Toronto. PARTICIPANTS: Hospitals were matched for location, acuity,
      and teaching affiliation. MAIN OUTCOME MEASURES: The numbers of beds occupied by
      patients awaiting transfer to nursing homes or chronic care hospitals were noted.
      RESULTS: In those teaching and community hospitals that had introduced
      coordinated geriatric and discharge planning services, there was a reduction in
      the percentage of beds occupied by patients awaiting long-term care placement
      (average-51%), whereas in hospitals without geriatric services, the percentage of
      beds occupied by patients awaiting long-term care placement increased (average +
      25%) (P = .05 by Fisher's exact method, 95% confidence limit odds ratio 0,
      .9999). CONCLUSION: The introduction of coordinated geriatric and discharge
      planning services was associated with a decrease in the percentage of beds
      occupied by patients awaiting long-term care in both teaching and community
      hospitals.

PMID- 7636097
TI  - Death certificate reporting of dementia and mortality in an Alzheimer's disease
      research center cohort.

PMID- 7636098
TI  - Comorbidity and adverse clinical events in the rehabilitation of older adults
      after hip fracture.

PMID- 7636099
TI  - Polycythemia as a complication of testosterone replacement therapy in nursing
      home men with low testosterone levels.

PMID- 7636100
TI  - Epidemiology of gallstone disease in an older Italian population in Montegrotto
      Terme, Padua.

PMID- 7636101
TI  - Progressive forgetfulness and imbalance.

PMID- 7636102
TI  - Progress toward a restraint-free environment in a large academic nursing
      facility.
AB  - OBJECTIVE: To review the implementation and evolution of a successful physical
      restraint reduction program in a large nursing facility. INTERVENTION AND
      MEASUREMENTS: An initiative to reduce physical restraint began in March of 1990
      with formation of a Restraint Review Committee (RRC), which developed and guided
      a program of inservice education, policy change, and procedural innovation.
      Progress was measured by monthly prevalence surveys of restraint use, both unit
      specific and facility-wide. PATIENTS AND SETTING: The study took place in an 816
      bed not-for-profit nursing facility with academic affiliation and closed medical
      staff. Mean age of residents was 85.5; 74% were female and 26% male. RESULTS:
      Physical restraint prevalence in our facility was reduced from 39% to 4% over 3
      years, with marked decrease in variation among nursing units. Prevalence
      initially decreased to 20% after policy modifications and inservice education
      programs. Further innovations in procedure and policy resulted in continued
      reduction of physical restraint to 4%. The facility-wide rate of falls and
      accident-related injuries did not change over the 3-year period. Decrease in
      physical restraint was not accompanied by a change in the percentage of residents
      prescribed psychotropic medications such as benzodiazepines and neuroleptics.
      CONCLUSIONS: In response to the mandate to provide a least-restrictive
      environment, our institution has developed a successful system resulting in a
      dramatic reduction in physical restraint use. Changes in institutional culture
      and barriers to change are discussed, as well as issues of cost and
      generalizability.

PMID- 7636103
TI  - Prevention and treatment of pressure sores.

PMID- 7636105
TI  - What's wrong with ADLs?

PMID- 7636104
TI  - Hearing impairment in older adults: new concepts.
AB  - OBJECTIVE: To review present information about the epidemiology, etiologies,
      pathogenesis, evaluation, and quality of life aspects of hearing loss and to
      present an approach to rehabilitation for hearing loss in older adults. DESIGN: A
      survey of recent findings on the problem of hearing loss in older adults,
      efficacy of intervention with amplification, and new developments in intervention
      strategies. CONCLUSIONS: The complex nature of hearing problems in older adults
      involves changes in the auditory periphery as well as in the central mechanisms
      for processing sound input. These changes affect the social and emotional impact
      of the hearing disorder. The importance of understanding the many implications of
      hearing loss on quality of life is emphasized. Both older adults and immediate
      family members need information and advice about the consequences of age-related
      hearing loss. The physician has a key role in helping them to overcome negative
      attitudes toward a hearing handicap. For most older persons, hearing aids
      alleviate many of the handicaps of hearing impairment. For some older persons who
      do not benefit adequately from conventional hearing aids, assistive listening
      devices may be helpful. Many old persons and their relatives are reluctant to
      confront the reality of hearing handicap and try to hide the fact that they need
      sound amplification. One important future direction is to foster acceptance of
      hearing loss and to support the more open use of amplification systems.

PMID- 7636106
TI  - Protecting self-determination of dementia patients.

PMID- 7636107
TI  - A closer relationship with the British Geriatrics Society.

PMID- 7636108
TI  - Forging links with the British Geriatrics Society.

PMID- 7636109
TI  - Adverse reactions to Sinemet CR.

PMID- 7636110
TI  - Aging topic questions on residency inservice training examinations.

PMID- 7636111
TI  - Lymphoma and methyldopa therapy.
AB  - I describe a patient who developed a drug associated lymphoma with methyldopa
      attributable to hypersensitive reaction. Several forms of immunologic changes
      have been observed with methyldopa therapy. In general, they have been considered
      to be hypersensitive changes from the common development of hemolytic anemia,
      lupus, retroperitoned fibrosis, thrombocytopenia, and hepatitis.

PMID- 7636112
TI  - Effect of age and education on performance on the Mini-Mental State Examination
      in a healthy older population and during the course of Alzheimer's disease.

PMID- 7636113
TI  - Attitudes of physicians in the treatment of congestive heart failure in older
      adults.

PMID- 7636114
TI  - Must physicians ignore God?

PMID- 7636115
TI  - Digital imaging in clinical photography, Part 2.
AB  - Following Part 1 of this article in the previous issue in which the technical
      aspects of the system were explored, Part 2 looks at the use of the digital
      camera system in the clinical photographic studio.

PMID- 7636116
TI  - Graphic file compression on a Macintosh.
AB  - AutoDoubler, Compact Pro, DiskDoubler, StuffIt Deluxe, and StuffIt SpaceSaver
      compression applications for the Macintosh were tested for size of compressed
      files, and time to compress and expand. EPS, TIFF, PICT and Photoshop native
      format file types were used, in 1-bit, 8-bit greyscale, 8-bit colour (indexed),
      24-bit colour (red, blue, green (RGB)), and 32-bit colour (cyan, magenta, yellow,
      black (CMYK)) modes. JPEG compression is illustrated by comparing an uncompressed
      image with three images compressed at different rates.

PMID- 7636117
TI  - Development of a health information service using a videotex system.
AB  - A number of health databases is now available in Malaysia, but few are accessible
      to the general public. However, recently a service was launched nationwide via a
      videotex system to also target the Malaysia public. This service is provided by
      the School of Pharmaceutical Sciences, Universiti Sains Malaysia (USM) in
      collaboration with several Malaysian Government ministries and agencies. Access
      to health information via videotex, be it medical, pharmaceutical or
      environmental is viewed as an effective means of on-line information
      dissemination. It provides not only rapid retrieval but is also economical and
      interactive, particularly suitable for a developing country.

PMID- 7636118
TI  - Production of a small-circulation medical journal using desktop publishing
      methods.
AB  - Since its inception in January 1988, the Baylor University Medical Center
      Proceedings, a quarterly medical journal, has been published by the few staff of
      the Scientific Publications Office (Baylor Research Institute, Dallas, Texas,
      USA) using microcomputers and page-makeup software in conjunction with a
      commercial printing company. This article outlines the establishment of the
      journal; the steps used in the publication process; the software and hardware
      used; and the changes in design, content, and circulation that have taken place
      as the journal and the technology used to create it have evolved.

PMID- 7636119
TI  - Digital video microscopy for the undergraduate histology laboratory.
AB  - An undergraduate histology course was profoundly changed through the introduction
      of digital video microscopy. Students have access to a networked, Macintosh-based
      imaging laboratory where they can digitally capture, enhance, analyse, and media
      output microscope originated images. By increasing the access to image
      information, students are able to assume a more active inquiry mode in a
      microscope-based course. The technology allowed students to increase intellectual
      sharing among themselves and to leave 'digital legacies' for future classes.

PMID- 7636121
TI  - The first college of medical illustration in Paris (France)--two years'
      experience.
AB  - In September 1992, the first College Programme of Medical Illustration in Paris
      began at the Ecole Superieure des Arts et Industries Graphiques Estienne. There
      had previously been only one College of Medical Illustration in France-founded in
      1969 in Strasbourg. Paris, at the centre of the French scientific and medical
      environment, had only a few medical artists, the situation was therefore
      propitious to the creation of the College. How could a freelance medical artist
      establish a medical illustration college in a National Arts School? This is the
      account of the School's first two years' experience, in which a number of the
      problems faced by both students and tutors are discussed.

PMID- 7636120
TI  - Retinal topography with the Heidelberg Retina Tomograph.
AB  - The Heidelberg Retina Tomograph is a confocal laser scanning microscope designed
      for in vivo three-dimensional imaging of the posterior segment of the eye. Due to
      its ability to produce highly accurate and reproducible topographic images, this
      sophisticated technology can most effectively be applied to the evaluation of
      topography at and around the optic nerve head. The main application is seen to be
      the detection and monitoring of change which occurs in glaucoma.

PMID- 7636122
TI  - The preparation and planning of artwork for book publication: the artist's
      viewpoint.
AB  - When becoming involved in the production of artwork for book publications the
      medical artist must interact and work with publishers through whom authors'
      instructions are conveyed. Procedures and job titles vary from one publisher to
      the other and misunderstandings can lead to costly mistakes. From a typical
      publishing situation a common approach to medical artwork preparation for book
      publication is described that will prepare the medical artist to work in close
      cooperation with the publishing team.

PMID- 7636123
TI  - Networks--'the information superhighway'.

PMID- 7636124
TI  - The rise and fall of democratic universalism: health care reform in Italy, 1978
      1994.
AB  - In 1978, a sweeping reform created the first national health service of
      continental Europe: Italy's Servizio Sanitario Nazionale. This new scheme was
      based on the principle of "full democratic universalism": The state would provide
      free and equal benefits to every citizen and the organization of public health
      would subject to popular control, essentially through political parties. However,
      the severe problems encountered in implementing the reform design and rapidly
      increasing health expenditures soon eroded any consensus on this principle. Thus
      the 1980s and early 1990s witnessed a gradual shift to "conditional and well
      managed universalism." These latter principles stress the need to differentiate
      access to care according to some criterion to regulate demand and the need for
      efficient use of scarce resources through adequate valorization of managerial
      skills and the use of "market-type" incentives. An elaborated system of user
      copayments was introduced gradually, and in 1992 a "reform of the reform"
      profoundly changed the organizational framework of the Servizio Sanitario
      Nazionale. The new government elected in the spring of 1994 announced ambitious
      plans to partially dismantle public universal insurance. Although these plans may
      prove difficult, the potential to form an anti-universalistic coalition seems
      strong in the contemporary Italian health care arena.

PMID- 7636125
TI  - The effect of fixed payment on hospital costs.
AB  - New Medicare regulations have replaced the cost-based system of reimbursement of
      capital expenditures by hospitals with a fixed payment per case based on assigned
      diagnostic-related groups. For the first time, hospitals must pay the
      governmental share of their capital costs. At the same time, overall reform
      points toward more capitation or fixed payments from all payers. This article
      discusses possible responses to legislative and competitive reforms by hospital
      management and the resulting effectiveness of the changes. To identify the
      potential effect of capital payment reform, we highlight some of the key
      provisions and assumptions of the new regulations, discuss the management
      implications of a changed capital payment system, and explore alternative models
      of hospital investment behavior in a world where one price for services for all
      buyers is a probable scenario.

PMID- 7636126
TI  - It's the institutions, stupid! Why comprehensive national health insurance always
      fails in America.
AB  - We argue that the United States does not have comprehensive national health
      insurance (NHI) because American political institutions are biased against this
      type of reform. The original design of a fragmented and federated national
      political system serving an increasingly large and diverse polity has been
      further fragmented by a series of political reforms beginning with the
      Progressive era and culminating with the congressional reforms of the mid-1970s.
      This institutional structure yields enormous power to intransigent interest
      groups and thus makes efforts by progressive reformers such as President Clinton
      (and previous reform-minded presidents before him) to mount a successful NHI
      campaign impossible. We show how this institutional structure has shaped
      political strategies and political outcomes related to NHI since Franklin D.
      Roosevelt. Finally, we argue that this institutional structure contributes to the
      antigovernment attitudes so often observed among Americans.

PMID- 7636127
TI  - The horses and the jumps: comments on the health care reform steeplechase.

PMID- 7636128
TI  - The role of institutions and ideas in health care policy.

PMID- 7636129
TI  - Nativism, hollow corporations, and managed competition: why the Clinton health
      care reform failed.

PMID- 7636130
TI  - The Clinton presidency and health care reform.

PMID- 7636131
TI  - The public's contribution to congressional gridlock on health care reform.

PMID- 7636132
TI  - Don't blame the public for failed health care reform.

PMID- 7636133
TI  - The health care debate: all heat and no light.

PMID- 7636134
TI  - Stuck in neutral: big business and the politics of national health reform.

PMID- 7636135
TI  - From setting a national agenda on health care to making decisions in Congress.

PMID- 7636136
TI  - Health care reform in the 103d Congress: a predictable failure.

PMID- 7636137
TI  - Why Congress did not enact health care reform.

PMID- 7636138
TI  - So near, and yet so far: a Canadian perspective on U.S. health care reform.

PMID- 7636140
TI  - The aftermath of defeat.

PMID- 7636139
TI  - Hope in federalism? What can the states do and what are they likely to do?
AB  - Although ERISA is a barrier to state health care reform, its hurdle is not as
      formidable as the financial and political constraints that state governments
      face. As the states themselves confess, they cannot solve this problem alone
      (National Governors Association 1993); but if they must, they will focus on the
      incremental, "low-cost" reform options--insurance reforms and Medicaid managed
      care. Connecticut Representative Courtney perhaps summarized state sentiment
      best: "Maybe we shouldn't be using the word 'reform'; it raises expectations"
      (Spencer-Molloy 1994b). Indeed, states will proceed more cautiously now than just
      a year ago because the federal failure accentuated the political gamble of health
      care reform and made the future prospect of transferring federal funds to state
      governments appear very bleak. Unfortunately, such cautious reforms will not move
      us toward the goal of universal (or statewide) coverage, a goal that seemed
      within our grasp only two years ago.

PMID- 7636141
TI  - Reform redux.

PMID- 7636143
TI  - When physicians go wrong.

PMID- 7636142
TI  - A summer of discontent: press coverage of murder and medical care reform.

PMID- 7636145
TI  - Nosocomial outbreak of Salmonella typhimurium infection in a nursery intensive
      care unit (NICU) and paediatric ward.
AB  - A nosocomial outbreak of multidrug resistant Salmonella typhimurium in a Nursery
      Intensive Care Unit (NICU) and Paediatric ward is reported. Eight (16.6%) out of
      a total of 48 babies taken ill during this outbreak expired. Clinical
      manifestations included diarrhoea and fever. The organism was isolated from stool
      samples/rectal swabs of all the 48 cases and blood of 6 cases. An investigation
      was undertaken to trace the source of infection. The organism was isolated in
      pure cultures from three suction machines of NICU. The epidemic was immediately
      controlled with identification of the source but the question of how the suction
      machines were infected by this organism remained unsolved.

PMID- 7636144
TI  - Sociodemographic characteristics of HIV infection in northern India.
AB  - 134 patients testing positive for HIV antibody during the period 1986-1993 were
      included in the present study. An in-depth analysis of the subjects revealed that
      the adult males seemed to have the highest propensity for HIV infection in this
      part of the country. Marital status had no bearing on incidence and route of
      seropositivity. This was not so in females. Extramarital heterosexual contact was
      the mode of HIV acquisition in adults in contrast to blood transfusion in
      children. Clinically, most of these patients were still asymptomatic. At
      presentation, oral Candidiasis was common. Pneumocystis carinii pneumonia (PCP)
      was the leading cause of death.

PMID- 7636146
TI  - HIV infection among the high risk groups of Upper Assam.
AB  - Serum samples of 9350 individuals belonging to different high risk groups were
      tested for HIV Infection by ELISA and western blot technique. 9 samples were
      found to be positive. Two of them belonged to indigenous people of Assam and the
      infection was transfusion/transplant associated and acquired outside the state
      during the course of medical treatment. Two were IDUs from Nagaland requiring
      treatment in a local hospital at Dibrugarh, Assam. Five were from floating
      population temporarily residing in Assam with history of heterosexual
      promiscuity. Overall seropositivity rate was 0.97/1000. It is felt that HIV
      infection in Upper Assam has not penetrated deeply and is at a manageable level
      and the spread of infection can be prevented through IEC programmes.

PMID- 7636147
TI  - Serosurvey of chikungunya antibody in Calcutta metropolis.
AB  - Since its first isolation in Calcutta, in 1963, there have been many reports
      about epidemis of chikungunya virus infection in different parts of India.
      Calcutta experienced a concurrent epidemic of dengue and chikungunya between 1963
      and 1965. But after that there is no report about any chikungunya infection in
      Calcutta. During routine investigations it is found that chikungunya antibody is
      on the wane. The present survey for chikungunya antibody showed only 4.37% (n =
      17) seropositivity out of 389 sera tested. The highest (12.5%) seropositivity was
      observed in the age group of 51-55 years and no chikungunya antibody was detected
      in young and young adults. The findings suggest that chikungunya virus is
      disappearing from the Calcutta population.

PMID- 7636148
TI  - Congenital cytomegalovirus infection in Shimla Hills, Himachal Pradesh, India.
AB  - We came across some cases clinically suggestive of intrauterine infection which
      were confirmed to be congenital cytomegalovirus infection. A clinical profile of
      these patients is presented. Intracranial calcification was not seen in any of
      these patients. Mental retardation was profound in all the patients and all had
      hepatomegaly. Uncommon findings encountered included hydrocephalus, patent ductus
      arteriosus and corneal opacities. Other clinical findings and investigation are
      also discussed.

PMID- 7636149
TI  - Prevalence, group pattern, T pattern and seasonal variation of beta haemolytic
      streptococci in and around Shimla.
AB  - One hundred and seventy two strains of beta haemolytic streptococci were isolated
      from various clinical specimens over a period of one year. Group A was isolated
      in 69.70% and group C in 16.80 percent. Majority of the strains were isolated
      during winter season and only 21.00 percent in summer 93.30 percent strains were
      bacitracin sensitive and all were sensitive to penicillin. The most common T
      pattern among group A was found to be 5/11/12/27/44 followed by 3/13/B 3264.

PMID- 7636150
TI  - Laboratory evaluation of an ovipositional trap for mosquito adults Aedes aegypti
      (L.) (Diptera: Culicidae).
AB  - A trap was designed, fabricated and evaluated for trapping and killing
      ovipositing females of the yellow fever mosquito Aedes. aegypti. Water in which
      larval stages had previously dwelt for 48 hrs. formed the attractant source for
      ovipositing mosquito females. The trap was evaluated under different experimental
      conditions. Single choice and double choice experiments were performed with or
      without glue applied to inner surfaces, to determine trap efficacy. Effect of
      population size and alteration in assay conditions on percentage catch are
      discussed.

PMID- 7636151
TI  - Ten year longitudinal study of efficacy and safety of purified chick embryo cell
      vaccine for pre- and post-exposure prophylaxis of rabies in Indian population.
AB  - One thousand three hundred and seventy-five (1375) persons, who were vaccinated
      against Rabies with Purified Chick Embryo Cell (PCEC) vaccine from 1984 to 1993,
      were included in this ten-year longitudinal study, conducted to observe the
      consistency, immunogenicity, inocuity, safety and efficacy of PCEC vaccine under
      controlled trial and field conditions. The study period was divided into three
      phases. Phases I and II covered the premarketing controlled trial and Phase III
      the post-marketing serosurveillance study of the vaccine. During Phase I, fifteen
      healthy volunteers were given a pre-exposure regime of vaccine on Day 0, 7 and
      21, and the rest 15, simulated post-exposure regime on Day 0, 3, 7, 14, 30 and
      90. All the subjects had satisfactory antirabies antibody response with mean
      titres, of 7.08 and 5.72 I.U./ml respectively, and minimal side reactions. In the
      Phase II, from 1984-85, 56 persons with proven rabid animal bites were given post
      exposure vaccination and all had satisfactory antibody titres with mean titre of
      4.45 I.U./ml after 6th dose of vaccine and with minimal side reactions. 19 to 36
      months follow up after vaccination revealed no vaccine failures. In the Phase III
      post-marketing field study conducted from 1985 to 1993, 1289 persons reported to
      our Centre for consulation and antirabies antibody titre estimation following
      PCEC vaccination. One thousand two hundred and fifty-two (1252) persons took post
      exposure vaccination following bites by rabid animals, contact with an
      hydrophobia patient and 37 high risk personnel took pre-exposure
      vaccination.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7636152
TI  - An analytical presentation of drug resistance in Plasmodium falciparum and
      guidelines to formulate a drug strategy.
AB  - The present paper describes the advantage/limitation of presently available 'in
      vivo' methods to detect sensitivity status of Plasmodium falciparum to commonly
      used antimalarial drugs. The paper is based on a retrospective analysis of 890 P.
      falciparum cases and various parameters used to define the level of drug
      resistance. The presented quantification methodology with weightage system to
      different epidemiological variables of resistance may provide a guideline as to
      the level of parasite resistance, and a switch over to another antimalarial of
      firstline treatment which is of the considerable importance to provide early
      diagnosis and prompt treatment to avert the severe cases/deaths due to malaria.

PMID- 7636154
TI  - A simple technique for detection and isolation of Phlebotomous argentipes larvae
      from soil samples.

PMID- 7636153
TI  - Susceptibility of larvae of five species of mosquito vectors of Japanese
      encephalitis to insecticides from Kolar district, Karnataka.

PMID- 7636155
TI  - Prevalence of schistosomiasis and other intestinal helminth infections among
      senior primary school children in Makenene Sub-Division, Cameroon.
AB  - A study was carried out in four villages of Makenene Sub-Division some 85 km
      north-west of Yaounde, between November 1993 and March 1994 to assess the
      prevalence and intensity of schistosomes and other helminth infections among
      senior primary school pupils aged 9-16. An extensive questionnaire was used to
      collect sociodemographic information and information on water-related activities.
      The overall prevalence of S. mansoni infection was 228 (23.6%) while S.
      haematobium infection was practically non-existent 03 (< 1%). Infection rates
      with intestinal nematodes were very high, up to 98% in some villages. Prevalence
      rates of schistosomiasis varied significantly (P < 0.05) between villages with
      the highest (36.2%) recorded in Makenene. Infections with other parasite species
      encountered were significantly different (P < 0.01) while a marked association
      was observed between water contact activities and the distribution of S. mansoni
      infections. However, S. mansoni infection intensities were not significantly
      different (P > 0.05) between those with a history of previous infection and
      treatment and those without.

PMID- 7636156
TI  - The karyotypes of Calicophoron microbothrium and Carmyerius gregarius from
      Egyptian ruminants.
AB  - The karotypes of the two amphistomes Calicophoron microbothrium Fischoeder, 1901
      and Carmyerius gregarius (Looss, 1896), Stiles & Goldberger, 1910 from Egyptian
      ruminants were studied using the air drying technique. The two species have
      similar number of chromosomes (n = 9), but differ in chromosome morphology. All
      the chromosomes of C. microbothrium are subtelocentric, except the first and the
      fifth are metacentric, whereas the chromosomes of C. gregarius are
      submetacentric, subtelocentric and acrocentric. Some cells in the two species
      showed tetraploidy. The results are discussed in terms of the phylogenetic
      relationship of different amphistomes.

PMID- 7636157
TI  - The prevalence of Taenia solium metacestodes in pigs in northern Tanzania.
AB  - Eighty three carcasses of pigs were examined at three abattoirs in Moshi, Arusha
      and Mbulu in northern Tanzania. Taenia solium metacestodes were found in all the
      three abattoirs with an overall prevalence of 13.3%. During routine meat
      inspection in Kiboroloni, Moshi 6.2-6.9% of the pigs were found to harbour T.
      solium metacestodes. The mean number of hooks on the protoscolices was 27 and the
      length of the small hooks varied from 105 microns to 130 microns while that of
      the larger hooks varied from 168 microns to 174 microns confirming that the cysts
      were metacestodes of T. solium. Although cystlike lesions were recovered from
      livers of both pigs and cattle, no hooklets of sizes in the range of 5-37 microns
      were found indicating that no Taiwan Taenia metacestodes were recovered during
      carcass examination.

PMID- 7636158
TI  - Cross-resistance between Strongyloides venezuelensis and S. ratti in mice.
AB  - Cross-resistance between Strongyloides venezuelensis and S. ratti was tested in
      mice. The mice were immunized with S. ratti and challenged with infective
      filariform larvae or larvae recovered from the lungs of mice, of a heterologous
      species, S. venezuelensis. In this system, cross-resistance was expressed to the
      intestinal stage but not to the migrating stage of the parasite. Anti-interleukin
      (IL)-5 monoclonal antibody (mAb) treatment showed that peripheral blood
      eosinophilia after infection with both species of the genus Strongyloides was
      dependent on IL-5. Cross-resistance expressed to the intestinal stages was
      inhibited partially by injection of anti-IL-5 mAb.

PMID- 7636159
TI  - Schistosoma haematobium in the baboon (Papio anubis): assessment of protection
      levels against either a single mass challenge or repeated trickle challenges
      after vaccination with irradiated schistosomula.
AB  - Baboons vaccinated intramuscularly with three times 9000 20 krad irradiated
      Schistosoma haematobium schistosomula at monthly intervals were exposed
      percutaneously to either a single mass challenge of 3000 (VMC) or ten, weekly
      trickle challenges of 300 (VTC) normals S. haematobium cercariae. Unvaccinated
      mass (MCC) or trickle (TCC) challenge controls were exposed simultaneously.
      Faecal and urine egg production was delayed in the vaccinated groups which also
      had reduced adult, particularly female, worm recoveries. Total faecal, urine and
      tissue eggs were lower in the vaccinated groups, as also were the size of
      granulomata and the gross pathology and severity of inflammatory responses in the
      bladder and ureters, except for an increased proportion of tissue eggs in the
      livers of vaccinated animals. Differences in pathology between groups were less
      marked in the other organs. Most indices were reduced in the trickle versus the
      mass challenge control groups. Some of these trends were statistically
      significant, mostly in the trickle vaccination group (VTC), but others were not.
      Compared with the appropriate unvaccinated controls, the percentage reduction for
      the trickle challenge (VTC) group (73%) was three times greater than that of the
      mass challenge (VMC) group (23%). Overall, the protective effect of vaccination
      was more clearly demonstrated in the trickle than in the mass challenge groups.
      This conclusion is based on a single experiment. Nevertheless, because trickle
      infections probably approximate more closely to what humans receive naturally, it
      is recommended that they should be used for future testing of all potential
      vaccines in baboons.

PMID- 7636160
TI  - A bolus for the administration to cattle of metacercariae of the liver fluke
      Fasciola hepatica.
AB  - A gelatin-agar bolus, designed and developed for the administration of
      metacercariae of the liver fluke Fasciola hepatica, was evaluated in adult
      Holstein Friesian cattle. The metacercariae, enclosed within a gelatin capsule,
      were placed inside the bolus and delivered to each animal using an oesophageal
      balling gun. At slaughter, 13 weeks after challenge, an average of 25% of the
      challenge dose was recovered from each liver. This percentage recovery is similar
      to that obtained with other known methods. The new bolus, however, offers
      improved handling qualities. In addition, the bolus also has potential for
      improving a number of other techniques including those for the administration of
      other parasites, compounds or chemotherapeutic agents.

PMID- 7636161
TI  - The effects of freezing on the viability of Toxocara canis and T. cati
      embryonated eggs.
AB  - Suspensions of embryonated (L2) Toxocara canis and T. cati eggs were maintained
      under freezing conditions in order to study the impact on their long term
      viability. The eggs had been removed from the uteri of adult Toxocara spp. worms
      and the suspended in a 0.4% formalin solution before being frozen in 20 ml
      plastic tubes in the freezer compartment of a domestic refrigerator. Assessment
      of embryonated egg viability over a period of 34 days was conducted by
      microscopic examination under a high light intensity. Embryonated T. cati eggs
      were found to exhibit a greater resistance to freezing than those of T. canis. A
      difference in the size, design of the egg shell or the metabolism of the larval
      form may have accounted for the observed differences in the percentage
      viabilities over time between the two species of Toxocara.

PMID- 7636162
TI  - Echinococcus granulosus: observations on strobilar development in in vitro
      monophasic culture.
AB  - The in vitro cultivation technique of Echinococcus granulosus protoscoleces
      usually states the necessity of a biphasic medium with a solid protein substrate
      for strobilar development to take place; otherwise, in a monophasic medium,
      protoscoleces follow a vesicular development. However, in some monophasic
      cultures, the development of several strobilate individuals (in different
      quantities and stages of development, depending on the culture) were observed.
      The only known difference from cultures made previously and since, where the
      development was vesicular, was the batch of foetal calf serum used in the
      constitution of the liquid medium, and this is presumed to be the cause of this
      unexpected strobilar development.

PMID- 7636163
TI  - The biology of diplostomatid eyeflukes of fishes.

PMID- 7636164
TI  - The expanding horizons of infection control.

PMID- 7636165
TI  - Occupational risk of human immunodeficiency virus, hepatitis B virus, and
      hepatitis C virus infections among funeral service practitioners in Maryland.
AB  - OBJECTIVE: To estimate the risk of exposure and infection with bloodborne
      pathogens, a seroepidemiologic survey was conducted among funeral service
      practitioners (FSPs) in Maryland. METHOD: Of 262 members of the Maryland State
      Funeral Directors Association, 130 (49%) volunteered to participate in the study.
      In addition to a brief questionnaire, designed to assess both occupational and
      non-occupational risk factors for bloodborne pathogen infection, participants
      were screened for markers of human immunodeficiency virus (HIV), hepatitis C
      virus (HCV), and past hepatitis B virus (HBV). Titers for antibodies to hepatitis
      B surface antigen (anti-HBs) also were examined and compared with history of
      hepatitis B vaccination. RESULTS: Seroprevalence for HIV, HBV, and HCV infection
      was 0.8%, 4.6%, and 0%, respectively. Nearly 19% of participants reported at
      least one bloodborne exposure in the past 6 months. The one HIV infection and all
      but two of the HBV infections were correlated with well-established non
      occupational risk behaviors. Disposable gloves were worn by 96%, and eating,
      drinking, or smoking during embalming were infrequent. Sixty-one percent of FSPs
      reported having received one or more doses of hepatitis B vaccine at some time in
      the past. Of those who reported having received all three doses of vaccine, 67%
      had adequate titers to hepatitis B surface antibody, the marker of protection
      related to vaccination. CONCLUSION: Compared with prior studies of FSPs, this
      study found a low rate of occupational exposures and a high rate of hepatitis B
      vaccination, suggesting improved compliance with recommendations for preventing
      transmission of bloodborne pathogens in the workplace.

PMID- 7636166
TI  - An outbreak of handscrubbing-related surgical site infections in vascular
      surgical procedures.
AB  - OBJECTIVE: To investigate an outbreak of surgical site infections (SSI) in a
      vascular surgery unit. SETTING: A 60-bed unit of vascular surgery, where surgeons
      performed an average of 30 operations per month at the Hospital do Servidor
      Publico Estadual, a 1,000-bed tertiary care hospital in Sao Paulo, Brazil.
      DESIGN: We included in the case group nine patients who had limb amputations or
      arterial reconstructions, October 16 through 23, 1992. We included in the control
      group patients whose operations were performed within 30 days of the outbreak
      period. Control patients were matched for sex and type of operation. RESULTS: Six
      of 9 case patients experienced SSI, as compared with 3 of 18 control patients (P
      = .026) and 28 of 244 patients in the pre-epidemic period (P = .0002). Risk
      factors were identical for case and control groups. Factors assessed were
      American Society of Anesthesiology (ASA) status, duration of surgery, wound
      class, emergency status, remote site infections, preoperative length of stay, use
      of prophylactic antibiotics, and underlying diseases. Possible common sources
      also were analyzed. No differences were observed concerning hair removal,
      preoperative shower, wound dressing, and surgical team present in the operating
      room. During the outbreak period, the operating room was not provided with
      povidone-iodine, used in our hospital for skin cleansing and handscrubbing.
      Surgeons from all departments, including vascular surgery, used 2% iodine with
      70% alcohol for skin cleansing. Surgeons from other departments used this iodine
      solution for handscrubbing, but the vascular surgeons used plain soap for
      handscrubbing. No increases in SSI rates were reported in other services.
      Comparison of case and control groups for handscrubbing was statistically
      significant (P < .00001). After reinstitution of povidone-iodine, only one SSI
      was diagnosed in 13 vascular procedures. CONCLUSIONS: Although we could not
      demonstrate definitely that scrubbing with plain soap was related to SSI, we
      found a strong suggestion of this association.

PMID- 7636167
TI  - Validation of a bacteremia prediction model.
AB  - OBJECTIVE: To validate a previously published model for predicting bacteremia in
      hospitalized patients. DESIGN: Application of a published bacteremia prediction
      model to a prospective validation cohort of patients and comparison of its
      predictability to that found in the derivation cohort. SETTING: Urban, university
      affiliated, 550-bed public hospital. PATIENTS: The validation cohort consisted of
      342 patients with 559 blood culture episodes between October 14, 1992, and
      December 5, 1992. Each blood culture episode was scored based on the presence or
      absence of seven predictors of bacteremia and the findings compared with
      published results (derivation cohort). INTERVENTIONS: None. RESULTS: Application
      of the bacteremia prediction model to the validation cohort identified episodes
      with a low risk (3%) and a high risk (17%) for true bacteremia, similar to the
      findings in the derivation cohort (1% and 16%, respectively). Comparison of the
      predictions of the model in the two cohorts by receiver operator characteristic
      curve analysis revealed that the overall predictability of the model in the
      validation cohort was not as good as in the derivation cohort. CONCLUSIONS:
      Although the bacteremia prediction model did not perform as well overall in the
      validation cohort, the model still was able to clearly define two extreme groups:
      those with a low risk and those with a high risk for true bacteremia. This
      predictive capability may aid physicians in prescribing empiric antimicrobial
      therapy and also may be useful to hospital epidemiologists in assessing quality
      of care.

PMID- 7636168
TI  - Conjunctivitis in a long-term care facility.
AB  - OBJECTIVE: To determine the prevalence, incidence, and etiology of conjunctivitis
      in residents of a long-term care facility. DESIGN: Prospective surveillance of
      episodes of conjunctivitis during two 6-month periods. SETTING: Three-building,
      319-bed, multipurpose, long-term care facility including units for personal care,
      chronic care, palliative care, rehabilitation, respiratory rehabilitation, and
      chronic ventilator patients. RESULTS: The incidence of conjunctivitis on
      different units varied from 0.6 to 3.5 per 1,000 patient-days. One building had a
      significantly higher rate of acute conjunctivitis and, within that facility, the
      most highly impaired patients had significantly more disease. Patients with
      chronic conjunctivitis generally were admitted with conjunctivitis;
      institutionally acquired conjunctivitis proceeding to chronic conjunctivitis
      seldom was observed except on the chronic ventilator unit. Residents with chronic
      conjunctivitis were significantly more likely to have a diagnosis of glaucoma,
      ectropion, or entropion. Potential bacterial pathogens were isolated from 3 (21%)
      of 14 and 24 (38%) of 69 acute episodes for which cultures were available in the
      two study periods. Staphylococcus aureus was the most frequent pathogen isolated.
      Empiric therapy was usually with topical sodium sulamyd or gentamicin, with
      substantial interphysician variability in prescribing patterns. Symptom duration
      did not differ for episodes which did or did not receive topical antimicrobials.
      CONCLUSION: Conjunctivitis is common in this facility and occurs with increased
      frequency in more highly impaired residents. Most episodes may not be due to
      bacterial infection. Further study of optimal management approaches to
      conjunctivitis is necessary.

PMID- 7636170
TI  - Characterization of nosocomial strains of Enterobacter aerogenes by arbitrarily
      primed-PCR analysis and ribotyping.
AB  - OBJECTIVE: To study the spread of strains of Enterobacter aerogenes in our
      hospital in 1992 and 1993 by using two genotypic markers, and to evaluate these
      methods for the epidemiological investigation of this species. DESIGN: Ribotyping
      (using two endonucleases) and arbitrarily primed (AP)-PCR (using two different 10
      mer primers) were applied to the epidemiological typing of clinical strains of E
      aerogenes isolated from hospitalized patients. SETTING AND PATIENTS: The
      intensive care unit (ICU; 5 patients, 13 isolates), nephrology units (3 patients,
      5 isolates), and surgery units (2 patients, 2 isolates) of the university
      hospital of Saint-Etienne (France). RESULTS: Eight epidemiologically unrelated
      isolates, chosen as controls, exhibited distinct profiles, both by AP-PCR and
      ribotyping. Two clones of E aerogenes circulated in the ICU; both were isolated
      successively from samples of a single patient who stayed in the unit for almost 1
      year. A third clone was recovered from patients of surgery units. A fourth clone
      was shown to have infected patients of nephrology units. CONCLUSIONS: Ribotyping
      and AP-PCR appear to be reliable methods for typing E aerogenes strains
      implicated in nosocomial infection. The spread of independent clones of E
      aerogenes in different units of our hospital in 1992 and 1993 was demonstrated by
      both methods. This study emphasizes the need to choose the endonucleases or
      primers with care to obtain high discriminatory results in genotypic
      investigations.

PMID- 7636169
TI  - Infections caused by Staphylococcus aureus in a Veterans' Affairs nursing home
      care unit: a 5-year experience.
AB  - OBJECTIVES: To describe the frequency and patterns of infection caused by
      methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant S
      aureus (MRSA) infections in a single nursing home population and to determine the
      effect of MRSA's entry into the facility on subsequent experience with both MSSA
      and MRSA infections. DESIGN: Observational and descriptive. Surveillance data on
      nursing home-acquired infections were reviewed to identify all patients with MSSA
      and MRSA infections occurring during the 5-year period from 1987 to 1991. The
      medical records of these patients were reviewed retrospectively to collect
      additional information about the patients and their infections. SETTING AND
      PATIENTS: A 120-bed Veterans' Affairs nursing home care unit (NHCU) whose
      residents predominantly were elderly men with severe underlying diseases and
      functional impairments. RESULTS: During the 5-year study period, 40 MSSA and 28
      MRSA infections were acquired by NHCU residents. Twelve to 19 S aureus infections
      occurred each year. S aureus accounted for 13% to 17% of all NHCU-acquired
      infections during the years of study, occurring with a frequency of 0.29 to 0.47
      infections per 1,000 resident-care days. MRSA infections, first detected in 1988,
      accounted for an increasing percentage of S aureus infections in subsequent
      years, but this increase had little effect on the facility's overall infection
      rates, the composite S aureus infection rates, or the types of infections
      observed. MSSA and MRSA infections acquired in the NHCU were comparable. Both
      affected patients with severe underlying diseases and functional impairments.
      Pneumonia, urinary tract infections, skin and soft tissue infections, and
      conjunctivitis were the types of infections observed most frequently, accounting
      for 28%, 25%, 22%, and 15% of all S aureus infections, respectively. Four
      bacteremic infections occurred in the MSSA group, and five in the MRSA group (P =
      .47). Four of the MSSA and three of the MRSA infections resulted in death (P =
      1.0). Nine of the MSSA and 12 of the MRSA infections resulted in the patient's
      transfer to the associated acute care hospital for additional care (P = .13).
      CONCLUSIONS: In the NHCU setting, MSSA and MRSA infections were similar in terms
      of the types of residents affected, the sites involved, and the frequency of
      adverse outcomes. The entry of MRSA into the facility appeared to have no effect
      on the subsequent experience with NHCU-acquired infections caused by S aureus.

PMID- 7636171
TI  - FDA labeling requirements for disinfection of endoscopes: a counterpoint.
AB  - Endoscopes are used widely for the diagnosis and therapy of medical disorders. To
      prevent spread of nosocomial infection, all endoscopes should undergo thorough
      cleaning and high-level disinfection following each use. The Food and Drug
      Administration (FDA) has approved a user-friendly package label for one liquid
      chemical germicide that requires a 45-minute immersion at 25 degrees C to support
      a high-level disinfection label claim. Scientific data reviewed here suggest that
      one can achieve at least an 8-log reduction in M tuberculosis contamination with
      cleaning (4 logs) followed by chemical disinfection for 20 minutes (4 to 6 logs).
      The FDA should modify the label to state that if cleaning is accomplished using a
      standardized cleaning protocol, then a 20-minute immersion at 20 degrees C will
      be sufficient to achieve high-level disinfection.

PMID- 7636172
TI  - GAO releases report on VA hospitals and use of safer needle devices.

PMID- 7636173
TI  - Preparing for and surviving a JCAHO inspection.
AB  - Foresight and planning can reduce stress associated with a JCAHO survey.
      Important resources for the epidemiologist include the Comprehensive
      Accreditation Manual for Hospitals, recommendations from previous JCAHO surveys,
      and educational meetings. Communication with colleagues who have been reviewed
      recently is an invaluable means of preparing for future surveys. Finally,
      although JCAHO accreditation is important, it is equally important to realize
      that the primary purpose of quality improvement programs is to improve the
      structure, process, and outcome of care.

PMID- 7636174
TI  - An introduction to utility measurement in health care.
AB  - Key decisions regarding the introduction and optimal use of health technologies
      often are made on an ad hoc basis. Quantitative information on effectiveness, if
      incorporated into the decision-making process, would establish a reasoned and
      defensible basis for the introduction and optimal use of therapeutic
      technologies. Utility measures provide a single summary score of effectiveness
      which, when combined with cost information, permits the calculation of cost
      utility ratios for alternative technologies. A number of techniques have been
      developed to elicit utilities, including standard gamble, time trade-off, rating
      scales, the Quality of Well-Being Scale, and the Health Utility Index. No single
      method has been accepted yet as the gold standard. Selection therefore must be
      guided by the specific objectives of the assessment.

PMID- 7636175
TI  - EPA begins testing hospital disinfectants as sterilant testing program nears
      completion.

PMID- 7636176
TI  - Natural T cells. Cells that co-express NKRP-1 and TCR.

PMID- 7636177
TI  - Anatomical environment as a determinant in viral immunity.
AB  - The immune response is not monolithic. The phenotype of immunity is modulated by
      the range of environments that lymphocytes experience as they passage through, or
      lodge for a time in, both secondary lymphoid tissue and other organ systems.
      Although we are constrained to think in terms of the homogeneity characteristic
      of the tissue culture flask, the cellular events in particular in vivo sites can
      vary considerably. The profiles found for accessible "windows" such as the blood,
      tonsil, or spleen do not necessarily reflect the totality of the host response.
      The theme of anatomically related divergence in the effector and memory phases of
      immunity is developed here, using examples from experiments with viruses.

PMID- 7636178
TI  - Activated adhesion of CTL to MHC class I but not to fibronectin is inhibited by
      cis unsaturated fatty acids and phenylarsine oxide.
AB  - Binding of CTL to MHC class I or fibronectin is activated through TCR signaling.
      Once activated, CTL adhesion to MHC class I results in tyrosine phosphorylation
      of CTL substrates, phosphatidylinositol (PI) turnover, and degranulation.
      Although activated adhesion to fibronectin does not itself initiate PI hydrolysis
      or degranulation, these responses are amplified once they become activated. In
      the present study we have examined the effect of cis unsaturated fatty acids (FA)
      and phenylarsine oxide (PAO) on CD8-mediated adhesion of CTL to immobilized class
      I protein and on biochemical and functional events that are triggered by this
      adhesion. Previous studies have shown that FA and low concentrations of PAO
      inhibit specific tyrosine phosphorylation events and degranulation but have no
      effect on PI turnover or CTL-target cell conjugates. The present results show
      that pretreating CTL with cis unsaturated, but not saturated, FA and low
      concentrations of PAO (< 0.5 microM) inhibit soluble anti-TCR-triggered binding
      of CD8 to immobilized MHC class I, tyrosine phosphorylation of CTL substrates, PI
      turnover, and degranulation. Addition of cis unsaturated FA or PAO after CTL have
      been allowed to bind to immobilized class I protein did not affect the level of
      adhesion. In contrast, neither cis unsaturated FA nor PAO affected the TCR
      activated binding of CTL to fibronectin. These results suggest that activation of
      adhesion to the class I and fibronectin ligands involves divergent different
      pathways that can be distinguished by the FA and PAO agents.

PMID- 7636179
TI  - Latent membrane protein-1 induces cyclin D2 expression, pRb hyperphosphorylation,
      and loss of TGF-beta 1-mediated growth inhibition in EBV-positive B cells.
AB  - The normal cell cycle is regulated by several molecules, such as the tumor
      suppressor protein pRb, the G1 cyclins, the cyclin-dependent kinases, and their
      inhibitors. These regulators are targeted by negative growth regulatory signals,
      such as that provided by TGF-beta. Here, we show that the presence of either wild
      type EBV or its transforming latent membrane protein-1 (LMP-1) results in the
      loss of TGF-beta 1-mediated growth inhibition in human B cells. Chemical cross
      linking with 125I-labeled TGF-beta 1 showed an essentially normal TGF-beta
      receptor profile in EBV-positive and EBV-negative Burkitt's lymphoma cell lines,
      and these receptors were shown to be functional in transducing signals, as
      evidenced by the TGF-beta 1-mediated modulation of junB gene expression. However,
      TGF-beta 1 did not induce dephosphorylation of pRb in EBV (or LMP-1)-positive
      cells as opposed to EBV-negative cells, suggesting a dichotomy in the TGF-beta 1
      signaling pathway leading to separable gene regulatory and growth inhibitory
      responses. Furthermore, LMP-1 was found to induce the expression of cyclin D2;
      normal B cells or EBV-negative Burkitt's lymphoma cells do not express D-type
      cyclins. Taken together, these data point to a potential mechanism underlying EBV
      mediated B cell transformation whereby constitutive induction of key cell cycle
      regulators by LMP-1 can lead to pRb hyperphosphorylation and uncontrolled cell
      proliferation.

PMID- 7636181
TI  - Specificity of glycopeptide-specific T cells.
AB  - We examined the specificity of glycopeptide-specific CD4 T cells following
      procedures similar to those previously reported by us. The disaccharide galabiose
      (Gal alpha 1-4Gal) was attached to the middle of the 52-61 peptide of hen egg
      lysozyme. This peptide is well known to bind to I-Ak molecules. CBA/J mice were
      immunized and T cell hybridomas were derived from the popliteal lymph node T
      cells. For this study, we selected hybridomas that recognized galabiose
      conjugated to 52-61 at residue Ser 56. We demonstrate here that these hybridomas
      showed specificity for galabiose and not cellobiose (Glc beta 1-4Glc). Peptides
      containing galabiose at residue 53 did not stimulate the T cell hybridomas and
      neither did galabiose conjugated to the 34-45 peptide of HEL. Acetylation of the
      hydroxyl groups of the disaccharide resulted in loss of T cell reactivity. These
      results need to be contrasted with those in which the T cells were directed to
      galabiose, attached to the amino terminus of 52-61 or to Ser at residue 53. With
      these results, the fine specificity of recognition of the disaccharide was not
      apparent. Our results indicate two sets of glycopeptide-specific T cells. One is
      probably induced by a conformational change induced by the disaccharide on the
      peptide bound to class II MHC molecules. The second set contains elements of
      specificity for both the disaccharide and the peptide.

PMID- 7636180
TI  - Regulation of NK cell functions by TGF-beta 1.
AB  - The contribution of exogenous and endogenous TGF-beta 1 to human peripheral blood
      NK cell proliferation and activity in vitro was investigated. Exogenous bioactive
      TGF-beta 1 inhibited NK cell DNA synthesis and production of IFN-gamma, TNF
      alpha, and granulocyte-macrophage CSF (GM-CSF) by NK cultures consisting of > 98%
      CD56+ cells. The cytotoxic activity of NK cells was also weakly inhibited by
      exogenous TGF-beta 1. All TGF-beta 1-induced inhibitory effects occurred in the
      absence and presence of the NK cell-activating cytokines IFN-alpha, IL-2, and IL
      12. Unstimulated NK cell cultures expressed steady state TGF-beta 1 mRNA detected
      by Northern blot analysis and produced TGF-beta protein (1.6 ng/ml), as
      determined by ELISA. When NK cell proliferation was induced by IL-2, IL-12, IFN
      alpha, or a combination of IL-2 and IL-12, expression of TGF-beta 1 mRNA and
      protein was moderately and consistently reduced by approximately 20%, as compared
      with unstimulated control cultures. Unstimulated and rapidly proliferating NK
      cell cultures secreted primarily latent TGF-beta into their culture medium, as
      determined by the Mv1Lu bioassay. These results indicate that, in vitro,
      endogenous NK cell-derived TGF-beta 1 has no negative autocrine effect upon
      activation of NK cells by various cytokines.

PMID- 7636182
TI  - The ability of B cells to participate in allogeneic cognate T-B cell interactions
      in vitro depends on the presence of CD4+ T cells during their development.
AB  - We have assessed in vitro whether the absence of T cells in the natural
      environment of F1 hybrid mice influences the ability of their B cells to
      participate in an allogeneic interaction with CD4+ cells from parental mice. For
      this purpose, B cells from athymic CB6F1 nu/nu mice or from CB6F1 mice depleted
      in different T cell subsets were incubated in vitro with purified CD4+ BALB/c
      cells. Here, we show that B cells from CB6F1 nu/nu mice or from euthymic CB6F1
      mice depleted from birth of CD4+ cells were unable to respond to allogeneic
      stimulation with BALB/c CD4+ T cells, which produce normal levels of cytokines.
      The addition of dendritic cells from euthymic CB6F1 mice did not revert this
      defect. B cells from CB6F1 mice lacking CD4+ T cells showed a selective reduction
      in the expression of CD23. We found a complete restoration of both the CD23
      expression and the ability of CB6F1 nu/nu B cells to respond in vitro to an
      allogeneic stimulation by CD4+ cells in two instances: (1) after neonatal
      engraftment of a syngeneic thymus into CB6F1 nu/nu mice, which partially
      reconstitutes the mature T cell populations; and (2) after preincubation of B
      cells from CB6F1 nu/nu mice with high concentrations of rIL-4. However, the
      addition of an anti-CD23 mAb did not interfere with the polyclonal activation of
      CB6F1 B cells in this system. These results indicate that CD4+ cells play an
      important role in the functional maturation of B cells by promoting their ability
      to participate in allogeneic cognate T-B cell interactions.

PMID- 7636183
TI  - A hierarchy for integrin expression and adhesiveness among T cell subsets that is
      linked to TCR gene usage and emphasizes V delta 1+ gamma delta T cell adherence
      and tissue retention.
AB  - To define the relationship between T cell phenotype and adhesiveness, we examined
      T cell adhesion to endothelial cell, fibroblast, and epithelial cell monolayers
      as well as extracellular matrix proteins (collagen and fibronectin) using a three
      color flow cytometry-based adherence assay that minimizes basal adhesion levels
      and facilitates quantitative lymphocyte subtyping. Regardless of monolayer type,
      monolayer stimulation conditions, or T cell activation status, we found that the
      gamma delta-TCR-bearing T cells adhered more efficiently than alpha beta T cells.
      The difference was based predominantly on increased levels of activatable LFA-1
      (and to a lesser degree VLA-4) because: 1) it correlated precisely with
      inhibitability by anti-LFA-1 (and VLA-4) mAbs and the levels of LFA-1 (and VLA-4)
      on the cell surface, and 2) it persisted after maximal LFA-1 (and VLA-4)
      activation with phorbol dibutyrate. In contrast to most cases of alpha beta T
      cell behavior, gamma delta T cell adhesion to cell monolayers was not linked to
      memory status, i.e., there was no difference between naive V delta 1+ and memory
      V delta 2+ populations in levels of LFA-1 (or VLA-4) expression or LFA-1- (or VLA
      4-) dependent adhesion to cell monolayers. However, V delta 1+ cells exhibited
      higher levels of VLA-5 that correlated with an increased adhesiveness to
      fibronectin and to a 120-kDa fibronectin fragment (FN-120) that contains only the
      VLA-5-binding domain but not to type I collagen or to a fibronectin fragment (FN
      40) that binds only VLA-4. Taken together, the results define a hierarchy for
      integrin (LFA-1, VLA-4, and VLA-5) expression and consequent adhesion among T
      cell subsets that is linked to TCR gene usage (but not necessarily linked to
      memory status) and may thereby help to explain the accumulation and retention of
      V delta 1+ gamma delta T cells in epithelial and connective tissues.

PMID- 7636184
TI  - Immunologic self-tolerance maintained by activated T cells expressing IL-2
      receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance
      causes various autoimmune diseases.
AB  - Approximately 10% of peripheral CD4+ cells and less than 1% of CD8+ cells in
      normal unimmunized adult mice express the IL-2 receptor alpha-chain (CD25)
      molecules. When CD4+ cell suspensions prepared from BALB/c nu/+ mice lymph nodes
      and spleens were depleted of CD25+ cells by specific mAb and C, and then
      inoculated into BALB/c athymic nude (nu/nu) mice, all recipients spontaneously
      developed histologically and serologically evident autoimmune diseases (such as
      thyroiditis, gastritis, insulitis, sialoadenitis, adrenalitis, oophoritis,
      glomerulonephritis, and polyarthritis); some mice also developed graft-vs-host
      like wasting disease. Reconstitution of CD4+CD25+ cells within a limited period
      after transfer of CD4+CD25- cells prevented these autoimmune developments in a
      dose-dependent fashion, whereas the reconstitution several days later, or
      inoculation of an equivalent dose of CD8+ cells, was far less efficient for the
      prevention. When nu/nu mice were transplanted with allogeneic skins or immunized
      with xenogeneic proteins at the time of CD25- cell inoculation, they showed
      significantly heightened immune responses to the skins or proteins, and
      reconstitution of CD4+CD25+ cells normalized the responses. Taken together, these
      results indicate that CD4+CD25+ cells contribute to maintaining self-tolerance by
      down-regulating immune response to self and non-self Ags in an Ag-nonspecific
      manner, presumably at the T cell activation stage; elimination/reduction of
      CD4+CD25+ cells relieves this general suppression, thereby not only enhancing
      immune responses to non-self Ags, but also eliciting autoimmune responses to
      certain self-Ags. Abnormality of this T cell-mediated mechanism of peripheral
      tolerance can be a possible cause of various autoimmune diseases.

PMID- 7636185
TI  - Treatment with okadaic acid reveals strong threonine phosphorylation of CD18
      after activation of CD11/CD18 leukocyte integrins with phorbol esters or CD3
      antibodies.
AB  - The CD11/CD18 leukocyte integrins comprise three heterodimers involved in
      leukocyte adhesion. CD11/CD18 avidity may be regulated intracellularly, and the
      CD18 polypeptide has previously been shown to become phosphorylated in leukocytes
      after phorbol ester stimulation. The importance of phosphorylation in the
      regulation of CD11/CD18 avidity has, however, remained unclear. We have now
      activated T cells using phorbol esters, CD3, and CD44 Abs. Both phorbol ester and
      CD3 treatment activated protein kinase C. CD18 was shown to become more stably
      phosphorylated after phorbol ester treatment and more transiently so after CD3
      stimulation. The phosphorylation was strongly augmented by okadaic acid, a
      serine/threonine phosphatase inhibitor. While phorbol ester treatment caused
      phosphorylation mainly on serine, in okadaic acid-pretreated cells, both phorbol
      ester treatment as well as CD3 stimulation revealed strong threonine
      phosphorylation. Since earlier mutational studies have demonstrated the
      functional importance of cytoplasmic threonine residues in CD18, the threonine
      phosphorylation reported here indicates the role of threonine phosphorylation in
      the regulation of CD11/CD18 avidity.

PMID- 7636187
TI  - V(D)J recombination and allelic exclusion of a TCR beta-chain minilocus occurs in
      the absence of a functional promoter.
AB  - Transcriptional activation of rearranging Ag receptor gene segments has been
      hypothesized to regulate their accessibility to V(D)J recombination. We analyzed
      the role of a functional promoter in the rearrangement of the murine TCR beta
      chain locus using two transgenic minilocus constructs. These miniloci each
      contain an unrearranged V beta 8.3 gene. One has a wild-type V beta 8.3 gene, but
      the other has a V beta 8.3 gene with a promoter mutation that was previously
      shown to abrogate transcription in tissue culture. FACS analysis of thymus and
      lymph node cells from transgenic mouse lines showed that only the lines with the
      wild-type V beta 8.3 gene promoter express an 8.3 TCR beta-chain. Consistent with
      the protein expression data, V beta 8.3 gene transcripts were found only in the
      transgenic lines with the wild-type promoter. Using a quantitative PCR-based
      assay, it was shown that both types of transgenic lines recombine the V beta 8.3
      gene at similar levels. Rearrangement of the transgenes was normal with respect
      to thymic development and junctional reading frame. Interestingly, both types of
      miniloci also underwent allelic exclusion in that recombination was blocked by
      the expression of a rearranged TCR beta-chain transgene. We conclude that a
      functional V beta gene promoter is not necessary for proper V(D)J recombination
      to occur.

PMID- 7636186
TI  - A novel biologic function of serum amyloid A. Induction of T lymphocyte migration
      and adhesion.
AB  - In the course of an inflammatory response, the concentration of serum amyloid A
      (SAA), a hepatocyte-derived acute phase protein, increases up to 1000-fold above
      the normal level. Although SAA was previously thought to be immunosuppressive, we
      recently reported that SAA is a potent chemoattractant for monocytes and
      neutrophils. The present study shows that recombinant human (rh) SAA also induces
      directional migration of T cells in vitro. Phenotypic analyses revealed that CD4+
      and CD8+ T cell subsets were equally responsive to rhSAA, whereas CD45RA cells
      were also not selectively attracted by rhSAA. The T cell chemotaxis induced by
      rhSAA was inhibited by pretreatment of cells with pertussis toxin, suggesting the
      interaction of rhSAA with a G-protein-coupled receptor species. T cells
      pretreated with an optimal concentration of SAA exhibited enhanced adherence to
      human umbilical cord endothelial cell monolayers. Subcutaneous administration of
      rhSAA into huPBL-SCID mice caused the infiltration of human T lymphocytes at the
      injection sites by 4 h. These results suggest that SAA may play an important role
      in recruiting T lymphocytes, as well as neutrophils and monocytes into
      inflammatory lesions.

PMID- 7636188
TI  - Structure of the gene for the human myeloid IgA Fc receptor (CD89).
AB  - A better understanding of IgA's role in immunity requires insight in IgAR
      complexity. We have now isolated, characterized, and sequenced the gene encoding
      the prototypic human myeloid IgA FcR (CD89). The gene consists of five exons and
      spans approximately 12 kilobase pairs. The leader peptide is encoded by two
      exons, the second of which is 36 bp long and specifies the predicted peptidase
      cleavage site. A similar, but shorter (21 bp) mini-exon has been found in the FcR
      for IgG (Fc gamma R) genes, and the FcR for IgE (Fc epsilon RI alpha) gene (human
      and rodent). The third and fourth exons code for two homologous Ig-like domains.
      The final exon encodes a short extracellular region, a hydrophobic transmembrane
      region, and a short cytoplasmic tail. The sequence of the 5'-flanking region was
      determined, and one major and several minor transcription initiation sites were
      mapped by primer extension studies. A putative TATA box was located at an
      appropriate location relative to the start site. Southern blot analyses of
      genomic DNA confirm the restriction map generated from cloned DNA. These data
      define the Fc alpha R gene as a distantly related member of the IgR gene family.

PMID- 7636189
TI  - Mutational analysis of two DR alpha residues involved in dimers of HLA-DR
      molecules.
AB  - Crystallographic analysis of HLA-DR1 molecules reveals a "dimer of dimers" with
      two reciprocal salt bridges between Glu 88 and Lys 111 of the two DR alpha
      chains. To determine whether these amino acids are critical for Ag presentation,
      we generated a panel of human B cell transfectants expressing DR alpha chains
      with mutations at residues 88, 111, or both. The mutant DR alpha chains, paired
      with endogenous DR3 beta chain, form cell surface dimers that retain epitopes
      recognized by a panel of anti-DR3 Abs. Replacement of Glu 88 with Ala (88A)
      selectively eliminates the ability to activate an alloreactive (anti-DR3) T cell
      clone. Mutant DR molecules with Lys substituted for Glu 88 (88K) fail to activate
      an alloreactive, an Ag-specific, and a peptide-specific T cell line. The DR alpha
      88 mutants bind an exogenously supplied DR3-specific peptide and the mutant DR
      molecules migrate as dimers on SDS-PAGE, implying that their defective Ag
      presentation is not due to an inability to bind antigenic peptides. In contrast,
      substitution of Lys 111 with either Ala (111A) or Glu (111E) does not abrogate Ag
      presentation. Further, the defect introduced by Glu 88 to Lys mutation (88K) is
      not overcome by compensatory Lys to Glu mutation at position 111 (111E). Taken
      together, these results indicate an important functional or structural role for
      position 88 of the DR alpha chain, but argue against a requirement for
      interaction between DR alpha 88 and 111 during Ag-specific T cell stimulation.

PMID- 7636190
TI  - Kinetic analysis of the interactions of recombinant human VpreB and Ig V domains.
AB  - The surrogate light chain, composed of VpreB and lambda 5/14.1 proteins, is
      selectively expressed on B cell precursors, and is important for B cell
      development. The surrogate light chain associates with cell surface mu-chains on
      preB cells, but little is known about the ligand specificity and affinity of
      VpreB binding. To analyze its interactions with Igs, we made recombinant human
      VpreB protein and measured its affinity for H and L chain V domains using surface
      plasmon resonance. The recombinant VpreB protein existed as a homodimer in
      solution. VpreB chains associated with each other with an apparent Kd = 5 x 10(
      7) M, and bound to a human VH domain, a mouse VH domain, and a human VL domain
      with a similar affinity. VpreB protein also bound to human Fab fragments of IgG
      with an apparent Kd = 6 x 10(-7) M, but showed a very low affinity for human Fc
      fragments of IgG. VpreB-Fab complex formation was reproduced by the formation of
      a trimolecular VpreB-VH-VL complex. Thus, VpreB proteins can associate with each
      other and also form complexes with Ig at sites different from those involved in
      VH-VL interaction. By flow cytometry, biotinylated VpreB protein bound to surface
      Ig-positive B cells but not T cells. Receptors that contain VpreB could be cross
      linked by either Ig or by self-association.

PMID- 7636191
TI  - Molecular analyses of the association of CD4 with two members of the
      transmembrane 4 superfamily, CD81 and CD82.
AB  - Previously, we have shown that CD81 and CD82, two members of the transmembrane 4
      superfamily, form multimolecular membrane complexes by associating with each
      other and with CD4 or CD8 in T cells. In the present study, we further analyzed
      the molecular basis of the CD4 association with CD81 and CD82 by co-precipitation
      experiments. First, we examined the regions of CD4 involved in the association
      with CD81 and CD82 by employing chimeric proteins generated from CD4 and CD2. It
      was confirmed that CD4, but not CD2, was capable of binding with CD81 and CD82 in
      transfected cells. We found that the cytoplasmic region of CD4 was sufficient for
      the chimeric proteins to co-precipitate CD81, while both the cytoplasmic and
      extracellular regions of CD4 were required for them to efficiently co-precipitate
      CD82. We next found, by using truncated CD4 lacking the C-terminal 31 amino acids
      or mutated CD4 with the cysteine residues at 394 and 397 replaced by serine, that
      the p56lck binding site or the covalent modification with palmitic acid was not
      necessary for CD4 to associate with CD81 and CD82. Finally, we found that the
      binding of p56lck to CD4 strongly inhibited its association with CD81 and CD82.
      It is, therefore, suggested that CD4 exists at least in two physical states, one
      associated with p56lck and another associated with CD81 and CD82 in the absence
      or uncoupling of p56lck.

PMID- 7636192
TI  - Multiple signals are required for function of the human granulocyte-macrophage
      colony-stimulating factor gene promoter in T cells.
AB  - The human granulocyte-macrophage CSF (GM-CSF) gene is expressed in T cells in
      response to TCR activation that can be mimicked by treatment of the cells with
      PMA and Ca2+ ionophore. The gene contains a proximal functional promoter region (
      620 to +34), as well as a powerful enhancer located 3 kb upstream, both of which
      are involved in the response of the gene to TCR activation. The proximal promoter
      contains a region termed CLEO (-54 to -31) that consists of a purine-rich element
      abutting an activator protein-1 (AP-1)-like site, as well as an upstream nuclear
      factor-kappa B (NF-kappa B) site (-85 to -76) and a CK-1 element (-101 to -92).
      We show in this work that mutations in either the purine-rich region of the CLEO
      element or the NF-kappa B site result in reduced PMA/Ca2+ activation of a 620-bp
      human GM-CSF promoter-luciferase reporter construct in Jurkat T cells by 65% and
      50%, respectively. The major inducible protein complex that binds to the human
      CLEO (hCLEO) element is an AP-1-like complex that is inducible by PMA alone, but
      shows increased binding in response to PMA together with Ca2+ ionophore. Although
      the binding of this complex is not cyclosporin-sensitive, promoter induction is
      inhibited by cyclosporin treatment. A second weak inducible complex resembling
      nuclear factor of activated T cells (NF-AT) was also observed binding to the
      hCLEO region. By using recombinant proteins, we confirmed that AP-1, NF-ATp, and
      a higher order NF-ATp/AP-1 complex could all form with the hCLEO element, and we
      have also defined the sequence requirements for binding of each of these
      complexes. We found that expression of a constitutively active form of
      calcineurin could substitute for Ca2+ ionophore and synergize with PMA to
      activate the GM-CSF promoter, and conversely that mutant-activated Ras could
      substitute for PMA and cooperate with Ca2+ ionophore. Co-expression of Ras and
      calcineurin, however, did not activate the GM-CSF promoter, but required the
      additional expression of NF-kappa B p65. These results imply that at least three
      signals are required to activate the GM-CSF proximal promoter, and that the
      signals impinge on distinct transcription factors that bind to the hCLEO and NF
      kappa B regions of the promoter.

PMID- 7636193
TI  - Conserved regions in the cytoplasmic domains of the leukocyte integrin alpha L
      beta 2 are involved in endoplasmic reticulum retention, dimerization, and
      cytoskeletal association.
AB  - Selected functions of integrins, including regulated cytoskeletal association and
      transmembrane signaling, depend on a poorly defined bidirectional communication
      between the extracellular and cytoplasmic domains of the alpha and beta subunits.
      To investigate this problem in the leukocyte integrin alpha L beta 2 (LFA-1), we
      generated a series of cytoplasmic truncation or internal substitution mutants of
      the alpha L and beta 2 cytoplasmic domains, and assessed their biochemical and
      functional properties upon ectopic expression in constitutively adherent cells.
      Expression of the alpha L beta 2 heterodimer in stably adherent cells is
      sufficient to promote its constitutive cytoskeletal association. Structural
      determinants for such association are located in selected regions of the beta 2
      cytoplasmic domain, which display functional interdependence. In addition, a
      conserved region (Arg733-Lys742) in the beta 2 cytoplasmic domain seems to be
      critical not only for its cytoskeletal association, but also for endoplasmic
      reticulum retention, assembly, and transport to the plasma membrane of the mature
      alpha L beta 2 heterodimer. Analysis of deletion mutants of the alpha L subunit
      demonstrates a role of the conserved, membrane-proximal GFFKR motif in conferring
      stability to the alpha beta complex, possibly because of its direct involvement
      in heterodimer formation. We propose that a previously uncharacterized
      association of defined subregions of the cytoplasmic domains of integrin alpha
      and beta subunits affects the dimerization and regulated function of the adhesion
      receptor.

PMID- 7636194
TI  - Selection for S107-V11 gene expression by peritoneal B cells in adult mice.
AB  - Peritoneal B-1 cells in adult mice express a restricted repertoire of V genes. To
      determine the basis for the nonrandom expression of one VH gene (the V11 gene in
      the S107 family), and to determine if this gene is nonrandomly expressed early in
      development, we amplified rearranged S107 genes in adult and neonatal tissues
      taken from B10.H-2aH-4bp/Wts (2a4b) mice. In adult peritoneal B cells, the S107
      V11 gene was found to be productively rearranged up to five times more frequently
      than V1, another member of the S107 VH gene family. This did not occur in adult
      spleen, or in neonatal spleen or liver. In these three tissues the productive
      S107-V11/V1 rearrangement ratios ranged from 0.5 to 0.9. This difference suggests
      that S107-V11-expressing peritoneal B cells in adult mice have been selected and
      clonally expanded. Clonal expansion is further suggested by the differing ratios
      of productive to nonproductive rearrangements. In adult peritoneal B cells, the
      S107-V11 productive/non-productive ratio is higher than that of V1, consistent
      with the clonal expansion of S107-V11-expressing cells but not of V1-expressing
      cells. Analysis of the VHDJH junctional sequences in the productive S107-V11
      rearrangements reveals that there are no predominant restrictions in the lengths
      or sequences of the third complementarity determining regions (CDR3). Selection
      is therefore independent of CDR3 and so must be based on germline-encoded
      portions of the S107-V11 region.

PMID- 7636195
TI  - Functional dissection of the murine lck distal promoter.
AB  - The lymphocyte-specific proto-oncogene lck is transcribed from two
      developmentally regulated, independently functioning promoters. The proximal
      promoter is used in thymocytes, but not in peripheral T lymphocytes. The distal
      promoter operates in all stages of T cell development, but predominates in more
      mature cells. Both promoters lack a TATAA element and they share little sequence
      similarity with each other. Using transgenic mice to locate in vivo functional
      cis-acting regions of the murine distal promoter, we defined a region from -1786
      to -2913 that is essential for consistent insertion site-independent expression
      of a heterologous cDNA reporter. The transgene is lymphoid specific and expressed
      predominantly in T cells. One of four transgenic mice bearing a shortened distal
      promoter (-886 to +41) expressed the reporter in the expected developmental
      pattern, suggesting that important regulatory elements that require favorable
      flanking sequences for expression are present nearer the transcription start
      site. The DNA sequence from -4032 to +623 contains few consensus binding sites
      for previously described T lymphocyte-specific trans-acting factors, and their
      locations do not correlate well with the functional data. However, the locations
      of tissue-specific modifications of chromatin structure in the promoter region,
      manifest as sites of DNase hypersensitivity, correlated with these two functional
      regions in normal mice. The identification of lck distal promoter regulatory
      regions provides a useful control element for deliberate expression of transgenes
      in mature T lymphocytes. In addition, these regulatory regions should assist in
      defining T cell-specific trans-acting factors.

PMID- 7636196
TI  - Anti-CD3 x anti-tumor F(ab')2 bifunctional antibody activates and retargets tumor
      infiltrating lymphocytes.
AB  - Bifunctional Abs (BFA) with specificity for the TCR/CD3 complex of T cells and
      tumor Ag can bridge T lymphocytes and tumor cells and, thereby, trigger
      activation events. The ability of intact and F(ab')2 anti-CD3 (500A2) x anti-p97
      (96.5) BFA to induce activation of T lymphocytes in the presence of murine
      melanoma tumor cells (CL-62) expressing human melanoma-associated Ag (p97) was
      investigated in vitro and in vivo. Intact and F(ab')2 BFA induced significant
      proliferation of T lymphocytes in the presence of p97+ tumor cells. Incubation of
      splenocytes with intact or F(ab')2 BFA and p97+ tumor cells increased BFA
      mediated cytotoxicity against relevant tumor cells. Intact BFA, in contrast to
      F(ab')2 BFA, induced some activation of T cells in vitro even in the absence of
      p97+ target cells. In nontumor-bearing mice, administration of F(ab')2 BFA, in
      contrast to intact BFA, did not increase cytotoxic activity of lymph node (LN)
      cells and splenocytes. However, when F(ab')2 BFA was administrated into CL-62
      bearing mice, an increase of BFA-mediated cytotoxicity of tumor-infiltrating
      lymphocytes, but not splenocytes nor LN cells, was observed. Moreover, in D
      galactosamine-sensitized mice, injection of intact BFA (1 microgram/mice) induced
      100% lethality, whereas the same dose of F(ab')2 BFA was not toxic. These results
      demonstrate that F(ab')2 BFA can induce activation of cytotoxic lymphocytes only
      in the presence of relevant tumor cells, both in vitro and in vivo. That these
      activated lymphocytes can be redirected to lyse relevant tumor cells by the same
      BFA has important implications for the clinical application of BFA anti-tumor
      therapies.

PMID- 7636197
TI  - Plasminogen activator inhibitor type 2 prevents programmed cell death of human
      macrophages infected with Mycobacterium avium, serovar 4.
AB  - Although Mycobacterium avium is usually nonpathogenic in healthy individuals, in
      vitro infection of macrophages (M phi) from the majority of healthy donors
      induces death of the cells 2 wk after infection; this effect is in contrast to
      noninfected M phi, which survive for months in culture. We demonstrate here that
      treatment of normal M phi with indomethacin further shortens the life of these
      cells to 48 h after infection with M. avium. Indomethacin treatment of the M phi
      also prevents M. avium-dependent accumulation of mRNA-encoding plasminogen
      activator inhibitor type-2 (PAI-2), an inhibitor of urokinase-type plasminogen
      activator. Occurrence of nuclear condensation and DNA fragmentation in M phi
      pretreated with indomethacin and infected with M. avium indicates that the early
      death of these cells is caused by apoptosis. In contrast, priming of M phi with
      GM-CSF significantly prolongs their survival after M. avium infection and
      enhances M. avium-induced accumulation of PAI-2 mRNA. Most importantly, addition
      of PAI-2 is sufficient to prevent apoptosis of M phi infected with M. avium in
      the presence of indomethacin. Finally, M phi not treated with indomethacin also
      die of apoptosis 7 to 10 days after M. avium infection and can be rescued by PAI
      2. These studies indicate that production of PAI-2 by normal M phi as a
      consequence of M. avium infection inhibits programmed cell death, a mechanism
      that might serve to prevent the spread of the infection.

PMID- 7636198
TI  - Small amounts of exogenous IL-4 increase the severity of encephalitis induced in
      mice by the intranasal infection of herpes simplex virus type 1.
AB  - The effect of murine rIL-4 on the development of herpesvirus encephalitis (HSE)
      in mice infected intranasally with herpes simplex virus type 1 (HSV-1) was
      investigated. The mortality rates of mice infected with a 0.5 LD50 dose of HSV-1
      were greatly increased after the administration of rIL-4 at doses ranging from
      0.01 to 1.0 U/mouse 2 h before and 2, 4 and 6 days after the infection. In
      contrast, survival rates of mice exposed to a 5 LD50 dose of HSV-1 were clearly
      increased when these mice were treated with anti-IL-4 mAb. Cervical lymph node
      (CLN) cells and cerebrospinal fluid (CSF) cells from mice with HSE (HSE mice)
      produced IL-4 in their culture fluids when they were stimulated in vitro with HSV
      1 Ag. Increased amounts of HSV-1 infection in mice resulted in the increased
      production of IL-4 in the culture fluids of local lymphocytes. However,
      significant amounts of IL-4 were not produced in serum specimens or in culture
      fluids of spleen cells from HSE mice. IL-4 production in culture fluids of CLN
      and CSF cells from HSE mice was clearly reduced after treatment of HSE mice with
      anti-IL-4 mAb. Furthermore, IL-4 production by CLN and CSF cells was greatly
      enhanced when the cells were prepared from HSE mice previously treated with rIL
      4. The IL-4 was mainly produced from CD4+ T cells. These results demonstrate that
      small amounts of exogenous IL-4 increase the severity of HSE in HSV-1-infected
      mice through the increased production of IL-4 from local CD4+ T cells.

PMID- 7636199
TI  - Integration of mycobacterial lipoarabinomannans into glycosylphosphatidylinositol
      rich domains of lymphomonocytic cell plasma membranes.
AB  - Lipoarabinomannans (LAMs) are major Ags of the mycobacterial cell envelope where
      they apparently insert through a glycosylphosphatidylinositol (GPI) anchoring
      structure. LAMs induce host macrophages to secrete TNF-alpha, IL-1, and IL-6 and
      inhibit T cell proliferative responses. The mechanisms by which LAMs mediate
      these effects remain poorly understood. We show that LAMs were efficiently
      inserted into the plasma membranes of human and murine lymphomonocytic cells
      through their GPI anchor. Prior deacylation of LAMs abrogated this event.
      Phosphatidylinositol hexamannoside (PIM6), the GPI anchor of all LAMs,
      competitively inhibited LAM insertion. Deacylated PIM6 was not inhibitory. The
      hexamannoside glycan of PIM6 appears to be important for LAM insertion, since
      phosphatidylinositol from soybean, lacking the glycan core, was not as efficient
      an inhibitor. Interaction of LAM with target cells was influenced by the
      gel/fluid phase distribution of membrane lipids, suggesting a direct interaction
      of the LAM-GPI anchor with the membrane bilayer. The inserted LAMs were mobile in
      the plane of the membrane and interfered with Ab-mediated mobilization of the GPI
      anchored Thy-1 molecules. Further, LAMs were preferentially incorporated into
      isolated plasma membrane vesicles enriched in Thy-1. Our results strongly suggest
      that 1) interaction of LAMs with host lymphomonocytic cells is mediated through a
      preferential integration of LAM-GPI anchor into specialized plasma membrane
      domains enriched in endogenous GPI-anchored molecules, and 2) both the acyl
      chains and the mannoside core glycan of the LAM-GPI anchor contribute to the
      specificity of integration.

PMID- 7636200
TI  - TGF-beta is important in determining the in vivo patterns of susceptibility or
      resistance in mice infected with Candida albicans.
AB  - Resistance and susceptibility of mice to systemic infection with the fungus
      Candida albicans are associated with the preferential expansion of Th1 and Th2
      cells, respectively. In this study, endogenous production of TGF-beta was found
      to be increased soon after infection of healer mice with a live vaccine strain of
      the fungus, but down-regulated in nonhealer mice with virulent yeast challenge.
      Although not affecting the outcome of primary challenge, serologic ablation of
      TGF-beta in the former animals abrogated development of acquired resistance and
      resulted in impaired production of IL-12/IFN-gamma and higher expression of IL
      4/IL-10 at the time of reinfection with virulent yeast. A CD4+ population
      expressing the memory phenotype, CD44highMEL-14low, which appeared to be expanded
      by yeast infection of nonhealer mice, was similarly increased in the healer mice
      by anti-TGF-beta treatment. In vitro rTGF-beta impaired the candidacidal function
      of IFN-gamma-activated macrophages. Yet in nonhealer mice infected with virulent
      C. albicans, administration of rTGF-beta delayed progression of the disease,
      which was concomitant with the detection of lower levels of IL-4. In addition to
      previous evidence for an obligatory role of IFN-gamma and IL-12 in Candida-driven
      Th1 cell differentiation in vivo, the present data establish TGF-beta as a third
      cytokine, the presence of which may be required for optimal Th1 development
      leading to long-lived anticandidal resistance.

PMID- 7636201
TI  - Lipoarabinomannan inhibits nonopsonic binding of Mycobacterium tuberculosis to
      murine macrophages.
AB  - The initial phagocytic interaction between Mycobacterium tuberculosis and
      macrophages (M phi) in the lung is probably nonopsonic, which would mean that M
      phi receptors will bind directly to bacterial ligands without the involvement of
      serum opsonins. Lipoarabinomannan (LAM) is a major component of the cell wall of
      mycobacteria. The possibility that LAM is involved in the nonopsonic binding of
      M. tuberculosis to M phi was investigated by using competitive inhibition assays.
      LAM inhibited binding of M. tuberculosis to murine peritoneal M phi in a dose
      dependent manner. LAM also inhibited the binding of Mycobacterium avium and
      Mycobacterium bovis BCG to M phi. Phosphatidylinositol mannoside and lipomannan
      have the same phosphatidylinositol (PI) moiety as LAM, but differ in their
      glycosylation patterns. Both molecules inhibited binding of M. tuberculosis to M
      phi. Deacylation of LAM abrogated its capacity to inhibit binding of M.
      tuberculosis to M phi. These observations indicated that it was the PI moiety of
      LAM that was important in mediating its inhibitory properties. In support of this
      hypothesis, commercial PI was shown to inhibit the binding of M. tuberculosis to
      M phi. Our results suggest that cellfree LAM is able to inhibit the binding of
      mycobacteria to M phi, but that it does not do so by competing with any
      interaction between M phi receptors and cell-associated LAM, because the PI end
      of the molecule is believed to be anchored in the bacterial plasma membrane, and
      therefore not available as a ligand on the cell surface. However, LAM that is
      released from M. tuberculosis in the course of its active replication during
      infection may be able to interfere with the phagocytic clearance of mycobacteria.

PMID- 7636202
TI  - Characterization of the gene encoding the polymorphic immunodominant molecule, a
      neutralizing antigen of Theileria parva.
AB  - Theileria parva, a tick-transmitted protozoan parasite related to Plasmodium
      spp., causes the disease East Coast fever, an acute and usually fatal
      lymphoproliferative disorder of cattle in Africa. Previous studies using sera
      from cattle that have survived infection identified a polymorphic immunodominant
      molecule (PIM) that is expressed by both the infective sporozoite stage of the
      parasite and the intracellular schizont. Here we show that mAb specific for the
      PIM Ag can inhibit sporozoite invasion of lymphocytes in vitro. A cDNA clone
      encoding the PIM Ag of the T. parva (Muguga) stock was obtained by using these
      mAb in a novel eukaryotic expression cloning system that allows isolation of cDNA
      encoding cytoplasmic or surface Ags. To establish the molecular basis of the
      polymorphism of PIM, the cDNA of the PIM Ag from a buffalo-derived T. parva stock
      was isolated and its sequence was compared with that of the cattle-derived Muguga
      PIM. The two cDNAs showed considerable identity in both the 5' and 3' regions,
      but there was substantial sequence divergence in the central regions. Several
      types of repeated sequences were identified in the variant regions. In the Muguga
      form of the molecule, there were five tandem repeats of the tetrapeptide, QPEP,
      that were shown, by transfection of a deleted version of the PIM gene, not to
      react with several anti-PIM mAbs. By isolating and sequencing the genomic version
      of the gene, we identified two small introns in the 3' region of the gene.
      Finally, we showed that polyclonal rat Abs against recombinant PIM neutralize
      sporozoite infectivity in vitro, suggesting that the PIM Ag should be evaluated
      for its capacity to immunize cattle against East Coast Fever.

PMID- 7636203
TI  - T cells infiltrating non-Hodgkin's B cell lymphomas show altered tyrosine
      phosphorylation pattern even though T cell receptor/CD3-associated kinases are
      present.
AB  - Although tumor infiltrating lymphocytes (T-TIL) from B cell non-Hodgkins lymphoma
      patients contain tumor-reactive T cells, they display poor proliferation and IFN
      gamma production when stimulated through the TCR-CD3. To determine if there was
      altered signaling linked to TCR-CD3 ligation, tyrosine phosphorylation was
      examined in T-TIL because it represents an early and critical event in T cell
      activation. After stimulation with anti-CD3 Ab, Western blotting with anti
      phosphotyrosine showed reduced phosphorylation in T-TIL when compared with
      peripheral blood-derived T cells from normal individuals. The altered
      phosphorylation was not due to the reduced expression of signaling elements
      linked to the TCR-CD3 complex. T-TIL expressed normal levels of CD3 epsilon, TCR
      zeta chain, and the three tyrosine kinases, p56lck (Lck), p59fyn, and ZAP-70.
      However, in T-TIL, anti-Lck Ab reacted with a 60-kDa protein, which appears to be
      the phosphorylated form of Lck. Binding of anti-Lck Ab to the 60-kDa protein was
      blocked by Lck peptide. In addition, anti-Lck Ab immunoprecipitated a
      phosphorylated 60-kDa protein from gamma-32P-labeled T-TIL that was not seen in
      normal resting T cells. In vitro kinase assay studies also demonstrated that TCR
      CD3 engagement increased the kinase activity of Lck in normal T cells but not in
      T-TIL. These results suggest that although T-TIL from B cell non-Hodgkins
      lymphoma patients contain the signal transduction molecules associated with TCR
      CD3 activation pathway, they are impaired in tyrosine phosphorylation and Lck
      activity, which may contribute to the functional defects of these cells.

PMID- 7636205
TI  - The serine/threonine phosphatase inhibitor, calyculin A, inhibits and dissociates
      macrophage responses to lipopolysaccharide.
AB  - LPS-stimulated macrophages (M phi) produce inflammatory mediators that are
      largely responsible for the pathophysiology associated with septic shock. M phi
      respond to LPS with rapid protein phosphorylation and dephosphorylation on
      serine, threonine, and tyrosine residues. If these events are critical for the
      cellular response to LPS, the kinases and/or phosphatases involved may be
      vulnerable targets for pharmacologic intervention. Recent studies demonstrated
      that tyrosine kinase inhibitors block LPS-induced tyrosine phosphorylation of MAP
      kinases as well as TNF-alpha and IL-1 beta production. To investigate a role for
      serine/threonine phosphatases, we evaluated the effect of calyculin A, a potent
      serine/threonine phosphatase inhibitor, on LPS stimulation of murine M phi.
      Pretreatment of M phi with calyculin A inhibited LPS-induced expression of six
      immediate-early genes: TNF-alpha, IL-1 beta, IFN-beta, IP-10, IRF-1, and TNFR-2.
      Calyculin A added 1.5 h after LPS treatment greatly reduced accumulation of IP
      10, IRF-1, and TNFR-2 mRNA, but not TNF-alpha, IL-1 beta, and IFN-beta mRNA.
      Calyculin A, in the absence or presence of LPS, resulted in sustained tyrosine
      phosphorylation of the MAP kinases. These findings suggest that an "early"
      serine/threonine phosphatase activity is essential for LPS stimulation of M phi
      and that the activation of MAP kinases is not sufficient for the induction of
      these immediate-early genes. The requirement for a "late" phosphatase activity
      for expression of a subset of LPS-inducible genes dissociates at least two
      regulatory pathways in LPS signal transduction.

PMID- 7636204
TI  - Cancer immunotherapy of established tumors with IL-12. Effective delivery by
      genetically engineered fibroblasts.
AB  - IL-12 is a heterodimeric cytokine produced by macrophages, mitogen stimulated- or
      EBV infected-B lymphocytes, keratinocytes, and probably dendritic cells, with
      important immunoregulatory functions in vitro and in vivo. It directly stimulates
      activated NK and T cells to produce high levels of IFN-gamma, enhances their
      cytolytic activity, and promotes maturation of Th1 cells as well as IL-2
      activated B cells. We have tested paracrine delivery of IL-12 using autologous or
      allogeneic fibroblasts engineered to secrete high levels of IL-12 to treat
      established tumors. Injection of IL-12-engineered fibroblasts at the site of an
      established (day 8) MCA207 sarcoma could efficiently eliminate or suppress tumor
      growth in a dose-dependent manner, requiring delivery of > 150 ng/kg/dose of
      bioactive IL-12. Weekly inoculations for 3 wk could also be used to effectively
      treat a day 4 sarcoma located intradermally in the opposite flank (80% protection
      using autologous fibroblasts), resulting in long-term protective antitumor
      immunity. In less immunogenic tumors (MCA102, MC38), 7-day established lung
      metastases could be significantly reduced (p = 0.001) following IL-12 delivery by
      fibroblasts and systemic administration of low doses of IL-2. Histologic findings
      included a mixed infiltrate of CD4+ and CD8+ T effectors and macrophages in the
      regressing sarcoma on day 21. In a day 41 MCA207 sarcoma locally injected in
      situ, similar findings were observed. No lymphoid hyperplasia or tissue necrosis
      were noted in liver, spleen, or lungs in mice receiving repeated inocula of IL-12
      engineered fibroblasts. Tests of liver and renal function monitored during the
      repetitive weekly treatments were within the normal range. IL-12-engineered
      fibroblasts thus seem to serve as a safe and efficient means to deliver IL-12 in
      these three tumor models.

PMID- 7636206
TI  - IL-4 inhibits IL-2-induced tumoricidal activity and secretory functions of human
      monocytes. Modulation of IL-2 binding and IL-2 receptor beta gamma chain
      expression.
AB  - Human monocytes express functional IL-2 receptors (IL-2R) and are directly
      activated by IL-2 to exert effector and secretory functions. In this study, we
      show that IL-4 selectively suppressed, in a dose-dependent manner, IL-2-induced
      monocyte tumoricidal activity, without affecting IFN-gamma-dependent
      cytotoxicity. This effect was specific because a neutralizing anti-IL-4 mAb
      completely restored IL-2-activated cytolysis. Furthermore, IL-4 effectively
      blocked the secretion of proinflammatory cytokines by IL-2-stimulated monocytes.
      Binding studies with biotin-conjugated IL-2 demonstrated that monocyte
      stimulation with IL-2 increased IL-2 binding to the cell surface, and that
      treatment with IL-4 inhibited this augmentation, providing a possible explanation
      for the decreased responsiveness of monocytes to IL-2 in the presence of IL-4.
      However, IL-4 suppressive effects could not be ascribed to the down-regulation of
      the individual components of the IL-2R complex. In fact, co-treatment of
      monocytes with IL-2 and IL-4 increased the expression of IL-2R gamma chain above
      the levels induced by IL-2 alone, whereas it did not significantly affect the
      expression of IL-2R beta chain. Thus, the inhibition of IL-2 binding by IL-4 may
      be due to the recruitment of the gamma chain into the IL-4-IL-4R system, making
      it unavailable for participation in the formation of IL-2 binding sites. These
      findings provide the first evidence of the ability of IL-4 to suppress IL-2
      mediated activation of human monocytes and suggest that IL-4 may play an
      important role in vivo as an inhibitory signal that controls the response of
      monocytes to IL-2.

PMID- 7636207
TI  - Inhibition of IL-10 expression by IFN-gamma up-regulates transcription of TNF
      alpha in human monocytes.
AB  - Stimulation of human monocytes with LPS induces expression of multiple cytokines,
      including TNF-alpha, IL-1 beta, IL-6, and IL-10, IL-10 expression is delayed
      relative to that of TNF-alpha, IL-1 beta, and IL-6. Furthermore, IL-10 feedback
      inhibits expression of TNF-alpha, IL-1 beta, and IL-6, thus providing an
      efficient autocrine mechanism for controlling proinflammatory cytokine production
      in monocytes. The Th1-type lymphokine, IFN-gamma, markedly up-regulates TNF-alpha
      production in monocytes. However, the precise mechanism by which IFN-gamma
      mediates this effect is unknown. We examined the effects of IFN-gamma on IL-10
      expression in LPS-stimulated monocytes, and the relationship between IL-10 and
      TNF-alpha production in these cells. LPS stimulation induced rapid, ordered
      expression of multiple cytokines. Steady-state mRNA levels for TNF-alpha
      increased rapidly, reached maximal levels by 2 to 3 h poststimulation, and then
      declined sharply. IL-1 beta and IL-6 mRNA levels also increased markedly
      following stimulation with LPS, but decreased more slowly than did TNF-alpha.
      Down-regulation of mRNA for TNF-alpha, IL-1 beta, and IL-6 coincided with a
      delayed and more gradual increase in IL-10 mRNA levels. Furthermore,
      neutralization of IL-10 with anti-IL-10 Abs prolonged TNF-alpha mRNA expression,
      and significantly increased net TNF-alpha production. IFN-gamma suppressed
      expression of IL-10 mRNA and protein in a dose-dependent manner. Moreover,
      inhibition of IL-10 production correlated with a marked increase in both the
      magnitude and duration of TNF-alpha expression. Thus, potentiation of TNF-alpha
      production by IFN-gamma in monocytes is coupled to inhibition of endogenous IL-10
      expression.

PMID- 7636208
TI  - IL-8 induces neutrophil chemotaxis predominantly via type I IL-8 receptors.
AB  - IL-8 is a potent proinflammatory cytokine that has a key role in the recruitment
      and activation of neutrophils during inflammation. IL-8 reacts with neutrophils
      via two distinct types of IL-8-R. Receptor-specific Abs were raised against
      peptides derived from the first extracellular domain of each IL-8-R. Anti-IL-8-R1
      and anti-IL-8-R2 selectively block 125I-IL-8 binding to rIL-8-R type 1 or 2,
      respectively. The anti-peptide Abs were used to assess the role of each receptor
      in the chemotactic response of neutrophils to GRO alpha and to IL-8. Anti-IL-8-R2
      blocks GRO alpha-induced chemotaxis of neutrophils. Chemotaxis to GRO alpha is
      not inhibited by anti-IL-8-R1. Thus GRO alpha stimulates chemotaxis exclusively
      through IL-8-R2 and independently of IL-8-R1. Surprisingly, anti-IL-8-R1 inhibits
      the majority (78 +/- 3%) of IL-8-induced neutrophil chemotaxis. Only a minor
      proportion of IL-8-induced chemotaxis (29 +/- 5%) is inhibited by anti-IL-8-R2.
      These findings indicate that chemotaxis to IL-8 is mediated predominantly by type
      1 IL-8-Rs and suggest that IL-8-R1 is an appropriate target for therapeutic
      strategies to limit neutrophil influx in diseases where neutrophils contribute to
      pathophysiology.

PMID- 7636209
TI  - Up-regulation of lung vascular ICAM-1 in rats is complement dependent.
AB  - Intrapulmonary deposition of IgG immune complexes in rats causes acute
      inflammatory lung injury that is neutrophil, complement, cytokines (IL-1, TNF
      alpha), and intercellular adhesion molecule (ICAM-1) dependent. In the current
      studies involving the same model of lung injury, complement depletion or
      complement blockade resulted in substantial reductions in up-regulation of
      pulmonary vascular ICAM-1, accompanied by reduced lung injury and neutrophil
      accumulation. Complement depletion neither reduced the amount of immune complex
      deposited in lung nor the TNF-alpha content in bronchoalveolar lavage fluids. In
      the same model of inflammatory lung injury, neutrophil depletion (which is highly
      protective) did not affect up-regulation of lung vascular ICAM-1. Up-regulation
      of lung vascular ICAM-1 by intratracheally administered TNF-alpha was also
      prevented by complement depletion. These studies indicate an unexpected in vivo
      relationship between complement and up-regulation of lung vascular ICAM-1.

PMID- 7636210
TI  - Characterization of latent TGF-beta activation by murine peritoneal macrophages.
AB  - Transforming growth factor-beta (TGF-beta) is secreted by most cells as a
      biologically inactive complex, called the large latent TGF-beta complex. The
      complex is comprised of latent TGF-beta binding protein (LTBP) and latent TGF
      beta, which is mature TGF-beta associated noncovalently with its amino-terminal
      propeptides. LTBP is disulfide-linked to the amino-terminal propeptide of latent
      TGF-beta. Active TGF-beta is generated by release of TGF-beta from the complex.
      Generation of active TGF-beta by macrophages has been reported, but the
      activation mechanism has not been described. Latent TGF-beta activation by
      macrophages was characterized using serum-free cultures of resident and
      thioglycollate-elicited murine peritoneal macrophages that were either
      unstimulated or LPS-stimulated in vitro. Serum-free conditioned medium was
      assayed for TGF-beta using a quantitative luciferase-based bioassay. LPS
      stimulated thioglycollate-elicited macrophages activated endogenous latent TGF
      beta, whereas non-LPS-stimulated thioglycollate-elicited and resident macrophages
      generated undetectable levels of TGF-beta. Latent TGF-beta activation required
      plasmin and urokinase (uPA), uPA binding to the uPA receptor, interaction with
      the cation-independent mannose 6-phosphate/insulin-like growth factor type II
      receptor, tissue type II transglutaminase, and LTBP. A time-course analysis of
      latent TGF-beta activation revealed that maximal TGF-beta was generated after 24
      h (25 +/- 5 pg/ml). TGF-beta formed within the initial 24 h modulated the
      plasminogen activator system by down-regulating uPA, suggesting that TGF-beta
      temporally modulated its own formation by regulating cell-associated uPA.

PMID- 7636211
TI  - Characterization of rat complement receptors and regulatory proteins. CR2 and
      Crry are conserved, and the C3b receptor of neutrophils and platelets is distinct
      from CR1.
AB  - In the mouse, CR1 and CR2 on B lymphocytes are encoded by alternatively spliced
      Cr2 gene transcripts. Immune adherence receptors that bind C3b are present on
      mouse platelets and unstimulated neutrophils, but they are not CR1. In this
      study, rabbit anti-mouse CR1/CR2 Ab immunoprecipitated a 145- to 150-kDa CR2
      protein from rat platelets, neutrophils, and splenocytes, but not a approximately
      200-kDa CR1 protein. By Northern analysis, cDNA for mouse CR2 hybridized to mRNA
      of 3.7 and 5.2 kb from both mouse and rat splenocytes. The murine decay
      accelerating factor and membrane cofactor protein analogue Crry was present in
      rat platelets, neutrophils, E, and splenocytes as two distinct proteins of 65 to
      70 kDa and 75 to 85 kDa. Rat platelets, neutrophils, and splenocytes contained a
      novel 200-kDa cell membrane protein that specifically bound to a rat C3b
      Sepharose column. We have named this protein C3bR-200. C3bR-200 was not
      identified by anti-mouse CR1/CR2 or anti-human CR1 Ab. Rat E lacked C3bR-200. Rat
      neutrophils and splenocytes also contained an 80-kDa C3b-binding protein that was
      distinct from Crry, which we have named C3bR-80. Therefore, CR2 and Crry are
      present in the rat, and have similar qualities to those from the mouse, except
      that CR2 is located on rat platelets and neutrophils, which is not the case in
      the mouse. Rat platelets, neutrophils, and splenocytes have a 200-kDa C3b-binding
      protein, C3bR-200, that is likely to be the rodent immune adherence receptor.

PMID- 7636212
TI  - Intercellular adhesion molecule-1 gene expression by glial cells. Differential
      mechanisms of inhibition by IL-10 and IL-6.
AB  - The central nervous system contains two major glial cell types, astrocytes and
      microglia, which function as immune effector cells within the central nervous
      system. We have been studying the ability of glial cells to express gene products
      involved in immune responsiveness, with an emphasis on expression of ICAM-1. We
      demonstrated previously that three proinflammatory cytokines, TNF-alpha, IL-1
      beta, and IFN-gamma, as well as IFN-gamma plus LPS, can enhance ICAM-1 expression
      by primary rat astrocytes. In this study, we examined ICAM-1 expression by
      primary rat microglia and found that only IFN-gamma and IFN-gamma/LPS enhance
      ICAM-1 gene expression. These data indicate that ICAM-1 expression by astrocytes
      and microglia is enhanced differentially by various proinflammatory cytokines. We
      next examined the effect of two cytokines, IL-10 and IL-6, on ICAM-1 expression.
      IL-10 alone has no effect on ICAM-1 expression, but it inhibits the enhancement
      of ICAM-1 intracellular and membrane protein expression in both cell types,
      although it has no influence on ICAM-1 steady-state mRNA levels. These results
      suggest that IL-10 affects ICAM-1 expression at the translational and/or post
      translational level. IL-6 alone also had no effect on ICAM-1 expression in either
      astrocytes or microglia, but it inhibited induction of both ICAM-1 mRNA and
      protein expression in these cells. Inhibition of ICAM-1 mRNA steady-state levels
      by IL-6 was not the result of degradation of the ICAM-1 message, suggesting an
      effect at the transcriptional level. Thus, both IL-10 and IL-6 can inhibit ICAM-1
      expression by glial cells, although they do so by contrasting mechanisms.

PMID- 7636213
TI  - Macrophage inflammatory protein-1 alpha mediates lung leukocyte recruitment, lung
      capillary leak, and early mortality in murine endotoxemia.
AB  - Systemic exposure to LPS initiates a complex sequence of events resulting in
      organ-specific leukocyte recruitment and end-organ injury. We hypothesized that
      macrophage inflammatory protein-1 alpha (MIP-1 alpha), a C-C chemokine with
      leukocyte chemotactic and activating properties, may play an important role in
      lung inflammatory cell recruitment, subsequent lung injury, and mortality in
      endotoxemia. CD-1 mice were challenged with LPS (200 micrograms), resulting in a
      maximal 3.5-fold increase in neutrophils (polymorphonuclear leukocytes (PMNs)) at
      6 h post-LPS, and a 2.6-fold increase in numbers of macrophages (M phi) within
      lung minces at 24 h. A time-dependent increase in MIP-1 alpha mRNA and protein
      was detected in lung after LPS treatment, with immunolocalization of MIP-1 alpha
      to blood and lung M phi, and the subendothelium. The pretreatment of mice with
      rabbit anti-MIP-1 alpha Ab resulted in a decrease in the influx of PMNs at 6 h,
      and influx of M phi at 24 h post-LPS challenge, an approximately 65% reduction in
      LPS-induced lung permeability to Evans blue, and a modest decrease in mortality
      at 24, but not 48 h post-LPS. Furthermore, passive immunization of mice with anti
      MIP-1 alpha serum resulted in a 35% reduction in ICAM-1 mRNA levels within lung
      homogenates post-LPS. Finally, the pretreatment of animals with sTNFR:Fc (soluble
      TNF receptor:Ig construct) resulted in a 60% reduction in LPS-induced MIP-1 alpha
      mRNA expression within lung homogenates at 4 h post-LPS. Our studies indicate
      that MIP-1 alpha plays an integral role as a mediator of both PMN and M phi
      recruitment in murine endotoxemia.

PMID- 7636214
TI  - Activation of p42mapk/erk2 following engagement of tumor necrosis factor receptor
      CD120a (p55) in mouse macrophages.
AB  - Cross-linking of the dichotomous cell surface receptors for TNF-alpha (CD120a
      (p55) and CD120b (p75)) induces the activation of a variety of macrophage
      responses that mediate the role of this cell in inflammation and host defense.
      Although significant progress has been made in understanding the role that lipid
      second messengers play in mediating the action(s) of this multifunctional
      cytokine, less is known about the role of specific kinases in TNF-alpha-initiated
      signaling. We show that exposure of mouse macrophages to TNF-alpha stimulates a
      rapid and transient tyrosine phosphorylation and activation of p42mapk/erk2. By
      contrast, p44mapk/erk1 was found to be constitutively phosphorylated, with
      minimal further response to TNF-alpha. To investigate the use of CD120a (p55) and
      CD120b (p75) in the activation of p42mapk/erk2 in mouse macrophages, we
      determined the effects of blocking Ab on the activation of p42mapk/erk2 in
      response to TNF-alpha. In addition, we independently cross-linked each receptor
      with specific agonistic Ab, which have previously been shown to mimic the effects
      of TNF-alpha. Collectively, the results from these experiments indicate that
      cross-linking of CD120a (p55), but not that of CD120b (p75), was both necessary
      and sufficient for the activation of p42mapk/erk2 in mouse macrophages.

PMID- 7636215
TI  - Identification of a novel class of mammalian Fc gamma receptor.
AB  - A cDNA encoding an Ig receptor that conferred the ability to bind erythrocytes
      sensitized with IgG2, but not IgG1, was cloned by screening a cattle alveolar
      macrophage library, made in the vector pCDM8, expressed in COS-7 cells. A search
      of the PIR database indicated a greater level of similarity with human Fc alpha R
      than with any other FcR. The percentage of identical amino acids was 41% and
      nucleotides 56%. This high similarity is between the extracellular and
      transmembrane domains; the cytoplasmic tails are unrelated. Similarities with
      human Fc gamma RI, Fc gamma RII, Fc gamma RIII, Fc epsilon RI, or bovine Fc gamma
      RII were less than 28%. COS-7 cells transfected with the cloned plasmid bound
      erythrocytes specifically sensitized with IgG2 but not with IgG1. In tests with
      heat-aggregated bovine Igs, IgG2 purified from serum bound to transfected COS-7
      cells but IgG1 from serum and IgA from tracheobronchial secretions did not. Human
      serum IgA also failed to bind to transfected COS-7 cells although it did bind to
      bovine neutrophils and monocytes. Only aggregated bovine IgG2 inhibited the
      binding of IgG2-sensitized erythrocytes to COS-7 cells transfected with the
      plasmid. These observations indicate that the FcR bound IgG2 specifically and was
      not a receptor for IgA. Thus, this receptor, which we have named bovine Fc gamma
      2R, represents a novel class of mammalian Fc gamma R, the evolution of which is
      likely to have been influenced by the truncated hinge of the bovine IgG2
      molecule. Analysis of genetic divergence of the genes encoding bovine and human
      Fc gamma R and Fc alpha R indicated that the novel bovine gene and the human Fc
      alpha R gene probably evolved from a common ancestor, which is not shared by
      other Fc gamma R.

PMID- 7636216
TI  - An anti-murine CD3 monoclonal antibody with a low affinity for Fc gamma receptors
      suppresses transplantation responses while minimizing acute toxicity and
      immunogenicity.
AB  - 145-2C11, a hamster mAb directed against the mouse CD3 complex, is a potent
      immunosuppressive agent. Upon initial treatment, 145-2C11 triggers a systemic
      release of multiple cytokines that is responsible for the acute toxicity of the
      mAb. This cellular activation is a consequence of the cross-linking between T
      lymphocytes and Fc gamma R-bearing cells, mediated by the high affinity of the
      hamster mAb for murine Fc gamma Rs. Repeated mAb injections result in the onset
      of a neutralizing humoral response. Therefore, there has been an increased
      interest in developing nonmitogenic forms of anti-CD3 mAbs, although it is not
      clear whether these Abs will retain immunosuppressive properties. To determine
      whether the initial cytokine production is necessary for the immunosuppressive
      properties and the immunogenicity of anti-CD3 mAbs in vivo, we have generated
      chimeric (hamster 145-2C11 F(ab')2 region/mouse Fc gamma portion) mAbs using
      murine isotypes with different affinities for Fc gamma Rs. The 145-2C11 and a
      chimeric IgG2a isotype, both of which bind murine Fc gamma Rs avidly, had similar
      activating, immunogenic, and immunosuppressive properties in mice. The
      administration of a chimeric IgG3 isotype with a very low affinity for murine Fc
      gamma Rs did not result in cytokine production, a humoral response against the
      mAb, or TCR desensitization. Nevertheless, prolongation of skin graft survival
      was similar in the IgG3, IgG2a, and 145-2C11-treated mice, indicating that Fc
      gamma R nonbinding anti-CD3 mAbs retain potent immunosuppressive properties in
      vivo while not being immunogenic. This enhanced therapeutic to toxic profile may
      be beneficial in clinical transplantation.

PMID- 7636217
TI  - Analysis of V beta 8.2 CDR3 sequences from spinal cord T cells of Lewis rats
      vaccinated or treated with TCR V beta 8.2-39-59 peptide.
AB  - Experimental autoimmune encephalomyelitis (EAE) in the Lewis rat can be induced
      with the administration of Gp-BP. This disease appears to be mediated at least in
      part by V beta 8.2+CD4+T cells, which specifically recognize the BP72-89
      encephalitogenic peptide. Treatment or protection with V beta 8.2 CDR2 39-59
      peptide can suppress or prevent clinical signs of EAE, presumably through the
      activation of regulatory T cells. Interestingly, V beta 8.2+ T cells continue to
      persist in the spinal cord of protected animals, although their appearance in the
      central nervous system (CNS) is delayed when compared with control animals with
      EAE. As part of our effort to elucidate the mechanism(s) of peptide protection
      and therapy, we sought to determine whether the V beta 8.2+ T cells in the spinal
      cord of protected or treated rats were truly representative of those found in
      rats with clinical EAE. Therefore, we examined the following CNS samples for the
      Asp96Ser97 motif, which has been identified previously in V beta 8.2+ BP
      specific, encephalitogenic T cell clones: 1) rats protected with V beta 8.2-39-59
      peptide, 2) rats treated with V beta 8.2-39-59 peptide, and 3) control rats with
      EAE. Our findings indicate that EAE-associated V beta 8.2+ sequences can still be
      found in both peptide-treated and peptide-protected rats. It appears that
      administration of V beta 8.2 CDR2 peptide does not prevent EAE-associated V beta
      8.2+ T cells from infiltrating the CNS and that other mechanisms are at work to
      prevent the development of EAE.

PMID- 7636218
TI  - HIV infection suppresses type 1 lymphokine and IL-12 responses to Toxoplasma
      gondii but fails to inhibit the synthesis of other parasite-induced monokines.
AB  - Individuals infected with Toxoplasma gondii normally develop resistance to the
      parasite, resulting in an asymptomatic chronic infection. In AIDS patients, this
      resistance is lost leading to reactivation of infection and development of
      encephalitis. To characterize the cytokine response of T. gondii-infected
      individuals, PBMC were cultured in vitro in the presence or absence of crude
      tachyzoite Ags (STAg). When stimulated with STAg, PBMC from T. gondii-infected
      donors, but not controls, produced high levels of Type 1 lymphokines (IL-2 and
      IFN-gamma) as well as the monokine IL-12, in the absence of detectable Type 2
      lymphokines (IL-4 and IL-5). In contrast, cells of individuals from both groups
      produced high levels of IL-1, IL-6, and TNF-alpha when exposed to the same Ag
      preparation. By using highly purified elutriated cells, we demonstrated that
      monocytes are a major source of these monokines. The above findings were further
      expanded by analyzing the cytokine responses induced by STAg in PBMC from
      patients co-infected with T. gondii and HIV. Our results demonstrate that
      parasite-specific IL-2 and IFN-gamma responses are greatly impaired even before
      AIDS development, as is IL-12 synthesis by PBMC from HIV-infected individuals
      stimulated with STAg. In contrast, the release of IL-6 and TNF-alpha triggered by
      STAg is either not affected or augmented during HIV infection.

PMID- 7636219
TI  - Autoimmunity induction by human T cell leukemia virus type 1 in transgenic mice
      that develop chronic inflammatory arthropathy resembling rheumatoid arthritis in
      humans.
AB  - We recently reported on an inflammatory arthropathy resembling rheumatoid
      arthritis that develops in high incidence among transgenic mice that carry the
      env-pX region of the human T cell leukemia virus type 1 genome. In an effort to
      elucidate the pathogenesis of this disease, we found that genes for inflammatory
      cytokines, including IL-1 alpha, IL-1 beta, IL-6, TNF-alpha, transforming growth
      factor-beta 1, IFN-gamma, and IL-2, as well as MHC genes were activated in
      transgenic joints. Serum levels of IL-1 beta and IL-6 were also elevated.
      Interestingly, these mice produced Ab against IgG, type II collagen (IIC), and
      heat shock proteins accompanied by IgG hypergammaglobulinemia. The cellular
      immune response to IIC as well as that to heat shock proteins were activated.
      Moreover, these mice became immunologically responsive to exogenously
      administered IIC and developed arthritis, in contrast to their nontransgenic
      littermates, which showed little response to IIC. Taken together, the results
      suggest that human T cell leukemia virus type 1 can cause immune system
      hyperreactivity and induce autoimmunity. The possibility that elevated cytokine
      and/or MHC gene expression are involved in the development of autoimmunity and
      arthropathy are discussed.

PMID- 7636220
TI  - Altered expression of monocyte IgA Fc receptors is associated with defective
      endocytosis in patients with alcoholic cirrhosis. Potential role for IFN-gamma.
AB  - Expression, saturation, and endocytosis of IgA Fc receptors (Fc alpha R) were
      analyzed in blood phagocytic cells of patients with alcoholic liver cirrhosis
      (ALC). Surface Fc alpha R expression was decreased in monocytes but not in
      neutrophils, as evaluated by IgA binding and anti-Fc alpha R mAb. The Fc alpha R
      of ALC patients were saturated by IgA1 and IgA2. ALC Fc alpha R had a higher M(r)
      (60 to 90 kDa) than those of controls (55 to 75 kDa) with a similar 32-kDa
      protein core after N-glycanase treatment, suggesting the expression of Fc alpha R
      molecules with altered carbohydrate moieties. Treatment of U937 cells with IFN
      gamma induced a decrease of surface Fc alpha R expression in a dose-dependent
      manner, with a similar M(r) as observed for ALC patient Fc alpha R (60 to 90
      kDa). Fc alpha R endocytosis was induced by anti-Fc alpha R or IgA. Neutrophils
      internalized Fc alpha R molecules faster than did monocytes. Endocytosed Fc alpha
      R co-localized with cathepsin D, suggesting an endolysosomal compartment pathway.
      In ALC monocytes, Fc alpha R endocytosis was defective, with nearly 50 to 60% of
      receptors detected on the cell surface even after 90 min at 37 degrees C.
      Similarly, delayed Fc alpha R endocytosis was observed on IFN-gamma-treated U937
      cells as compared with PMA-activated cells. Defective internalization of surface
      bound IgA with reflux of IgA to cell surface was also observed on ALC monocytes,
      but not on normal cells preincubated with patients' plasma, ruling out direct
      effects of IgA. The inverse correlation between monocyte Fc alpha R levels and
      serum IgA levels associated with defective endocytosis suggest that altered Fc
      alpha R expression might contribute to receptor saturation and generation of
      increased plasma levels of IgA and IgA-immune complexes in ALC patients.

PMID- 7636221
TI  - Induction of protective polyclonal antibodies by immunization with Plasmodium
      yoelii circumsporozoite protein multiple antigen peptide vaccine.

PMID- 7636222
TI  - Structure of the mouse CD72 (Lyb-2) gene and its alternatively spliced
      transcripts.

PMID- 7636224
TI  - The novelty of antigen-processing compartments.

PMID- 7636223
TI  - Regulation of antibody production and class switching by TGF-beta.

PMID- 7636225
TI  - Induction of tolerance to heart allografts in high responder rats by combining
      anti-CD4 with CTLA4Ig.
AB  - It has been difficult to induce donor-specific transplantation tolerance in high
      responder Lewis rats. Results presented below demonstrate that amounts of
      pretransplant anti-CD4 sufficient to allow allograft tolerance in low responder
      strains (5 mg/kg x 4 days) did not prevent the acute rejection of ACI heart
      allografts in high responder Lewis recipients. Higher doses of pretransplant anti
      CD4 (10 mg/kg, 15 mg/kg, and 20 mg/kg) given alone could delay but not prevent
      allograft rejection. Pretransplant anti-CD4 combined with anti-CD8, thymectomy,
      and total lymphoid irradiation all failed to produce tolerance to ACI heart
      allografts. However, a regimen of anti-CD4 combined with CTLA4Ig allowed
      indefinite survival of ACI heart allografts (mean survival time, > 100 day).
      Second-donor matched heart grafts were permanently accepted, and third-party
      heart grafts were permanently accepted, and third-party heart allografts were
      rejected by the tolerant recipients. These results suggest a new combination
      therapeutic strategy for clinical transplantation.

PMID- 7636226
TI  - Activation of src-related tyrosine kinases by IL-3.
AB  - The activation of src-related tyrosine kinases following IL-3 stimulation was
      examined in 32Dcl3 cells. Three src-related tyrosine kinases were activated
      following IL-3 stimulation: fyn, hck, and lyn. 32Dcl3 cells were transfected with
      retroviral vectors expressing each of these kinases and independent clones
      overexpressing each kinase were isolated. In cells overexpressing either fyn or
      hck, IL-3 stimulated a rapid increase in catalytic activity, which remained
      elevated longer compared with the kinetics observed in parental 32Dcl3 cells. An
      increase in the number of tyrosine-phosphorylated proteins in the presence and
      absence of IL-3 stimulation was observed in cells overexpressing fyn or hck.
      Transfection of 32Dcl3 cells with a retroviral vector encoding lyn also resulted
      in an elevated level of kinase activity, although the increase was not as
      dramatic as that observed with fyn or hck. Consistent with observations in
      parental 32Dcl3 cells, a high basal level of lyn kinase activity was observed in
      unstimulated lyn-transfected cells and IL-3 stimulation resulted in an
      approximate threefold increase in kinase activity. Overexpression of c-src in
      32Dcl3 did not result in IL-3-stimulated activation of c-src, indicating
      specificity for fyn, hck, and lyn. While the overexpression of fyn, hck, or lyn
      in 32Dcl3 cells resulted in increased kinase activity and IL-3 stimulated
      tyrosine phosphorylation, it did not render the cells more sensitive to IL-3.
      These results suggests that in addition to the JAK2 tyrosine kinase, src-related
      kinases may play a significant role in signal transduction by cytokine receptors.

PMID- 7636228
TI  - Characterization of intercellular adhesion molecule-1 (ICAM-1)-augmented
      degranulation by cytotoxic T cells. ICAM-1 and anti-CD3 must be co-localized for
      optimal adhesion and stimulation.
AB  - Purified intercellular adhesion molecule-1 (ICAM-1), a ligand of the LFA-1, was
      used to analyze the contribution of ICAM-1 to the activation of CTL. ICAM-1
      facilitates degranulation when co-immobilized with substimulatory amounts of anti
      CD3. This facilitated response is most likely mediated through LFA-1, since Abs
      to this molecule significantly inhibit the response, Interestingly, when ICAM-1
      and anti-CD3 are immobilized on separate beads and presented to the CTL, no ICAM
      1-enhanced degranulation is observed. The ICAM-1 and anti-CD3 must be immobilized
      on the same surface to augment the response, suggesting that ICAM-1 either does
      not transmit signals into the cell or it transmits a very localized signal, since
      the ICAM-1 and anti-CD3 must be juxtaposed. Consistent with this finding, we
      demonstrate that ICAM-1 does not induce tyrosine phosphorylation or a Ca(2+)-flux
      in the CTL clone, but does potentiate these responses when co-immobilized with
      substimulatory anti-CD3. Finally ICAM-1 and anti-CD3 must be immobilized on the
      same bead for stable adhesion of CTL to ICAM-1. When ICAM-1 and anti-CD3 are
      immobilized on separate beads, there is only a transient, low level of adhesion
      to the ICAM-1 beads. Taken together, these results suggest that LFA-1 is acting
      principally as an adhesion molecule, with respect to ICAM-1, in CTL and that this
      adhesion is regulated through the TCR complex.

PMID- 7636227
TI  - Lymphotoxin-alpha-deficient mice. Effects on secondary lymphoid organ development
      and humoral immune responsiveness.
AB  - Targeted mutagenesis in embryonic stem cells was used to generate mice deficient
      in lymphotoxin-alpha (LT-alpha). Mice lacking LT-alpha -/- (LT-alpha -/- mice)
      exhibit a phenotype dominated by defects in secondary lymphoid organ development.
      LT-alpha -/- mice lack lymph nodes and Peyer's patches, and possess spleens in
      which the usual architecture is disrupted. However, in a few of the mutants,
      abnormal lymph node-like structures were observed, mainly within the mesenteric
      fat. Abnormal clusters of lymphocytes were also found to accumulate in the
      periportal and perivascular regions of the liver and lung of LT-alpha -/- mice.
      Yet, lymphocytes from LT-alpha -/- mice appeared phenotypically normal,
      expressing the expected ratios of B and T cell surface markers as well as the
      lymphocyte homing marker, L-selectin. In addition, bone marrow cells from LT
      alpha -/- mice were able to successfully reconstitute the lymphoid organs of
      severe combined immunodeficient mice. However, LT-alpha -/- mutant mice examined
      for humoral immune responsiveness were found to be impaired in their ability to
      respond to different Ag. These data illustrate the utility of this mouse model as
      a system for understanding lymphoid organ development and its effects on immune
      responsiveness.

PMID- 7636229
TI  - Analysis of the CD4 coreceptor and activation-induced costimulatory molecules in
      antigen-mediated mature T lymphocyte death.
AB  - We have compared the signaling requirements for activation and lymphokine
      production in mature T lymphocytes to those required for TCR-driven programmed
      cell death (PCD). Both processes require TCR engagement and ligation of the CD4
      coreceptor in the case of a T cell clone that recognizes Ag in the context of an
      MHC class II molecule. By contrast, stimulation through the CD28/B7 pathway does
      not appear to positively or negatively influence TCR-induced PCD, although it was
      required for IL-2 production in both resting and proliferating T cells. T cells
      that had been activated and induced to proliferate with IL-2 were found to
      express high levels of IL-2 mRNA upon TCR rechallenge, without a requirement for
      accessory cells. This was due to a strong up-regulation of the B7-1 molecule, but
      not the B7-2 molecule, on the T cell surface. These T cells that strongly
      costimulate each other are highly susceptible to TCR-induced death providing
      independent evidence that costimulatory signals are not protective. Thus, these
      results provide evidence that in mature T cells there exists a difference in the
      requirement for CD28 to achieve activation and IL-2 production compared with TCR
      mediated PCD.

PMID- 7636230
TI  - The cytokines IL-4, IFN-gamma, and IL-12 regulate the development of subsets of
      memory effector helper T cells in vitro.
AB  - We analyzed the development of cytokine-producing effector T cells from resting
      CD4 memory cells. Previously we showed that such memory effectors are induced in
      vivo upon re-exposure to Ag. Here we demonstrate that effectors arise in vitro
      when memory CD4 cells are restimulated with Ag in the presence cytokines. Resting
      splenic CD4 cells from KLH-primed mice that were depleted of naive cells by adult
      thymectomy and were exclusively of memory phenotype initially secreted high
      titers of IL-2 and low levels of IL-4 and IFN-gamma in response to Ag. When
      memory CD4 cells were restimulated for 3 to 4 days in cultures containing rIL-2
      and Ab to block endogenous IFN-gamma and IL-4 secretion, Th0-like effectors that
      produced greatly increased levels of IL-2, IL-4, and IFN-gamma developed. rIL-4
      together with rIL-2 and anti-IFN-gamma induced Th2-like cells that secreted
      primarily IL-4. In contrast, Th1-like effectors that produced IL-2 and IFN-gamma
      developed in the presence of rIL-2 and anti-IL-4. Addition of rIFN-gamma further
      enhanced priming for IFN-gamma secretion. rIL-12 also induced effectors that
      produced high levels of IFN-gamma, but little IL-2. Thus, cytokines direct the
      development of effector subsets from memory CD4 cells. Our results suggest that
      memory and naive CD4 cells undergo parallel development following Ag stimulation,
      initially secreting predominantly IL-2 and differentiating in response to IL-4,
      IFN-gamma, and IL-12 into polarized effector subsets.

PMID- 7636231
TI  - Membrane and soluble Fc gamma RII/III modulate the antigen-presenting capacity of
      murine dendritic epidermal Langerhans cells for IgG-complexed antigens.
AB  - Murine dendritic epidermal Langerhans cells (LC) are APC. This implies that LC
      take up, process, and present Ag to T cells. One way of doing so that could allow
      Ag internalization is provided by the low affinity receptors for the Fc region of
      IgG (Fc gamma R), which murine LC are known to express, although their isoform(s)
      and function(s) have not been defined. By using molecular biology and biochemical
      approaches, we demonstrated that LC expressed Fc gamma RIIb2 and Fc gamma RIII.
      Furthermore, LC internalized Fc gamma R by receptor-mediated endocytosis, as
      observed with gold-labeled anti-Fc gamma RII/III mAb or immune complexes. We
      demonstrated the biologic relevance of this process by observing that Fc gamma R
      mediated Ag internalization improved by approximately 300-fold the Ag-presenting
      capacity of LC to T cells. Moreover, analysis of cell culture supernatants showed
      that two forms of soluble Fc gamma R (sFc gamma R) were released by LC: the first
      most probably was the secreted transmembrane-deleted Fc gamma RII isoform, Fc
      gamma RIIb3, and the second was a soluble receptor probably derived from the
      membrane-associated Fc gamma RII/III. The ability of two recombinant forms,
      corresponding to the two sFc gamma R released by LC, to inhibit Fc gamma R
      mediated presentation enhancement was assayed. Preincubation of IgG-complexed Ag
      with either rsFc gamma R led to a dose-dependent decrease in the Ag-presenting
      capacity of LC. Taken together, our results suggest that, in vivo, LC express
      membrane Fc gamma R, which increase their Ag-presenting capacity for IgG
      complexed Ag, and release sFc gamma R, which might be able to modulate this Ag
      presentation.

PMID- 7636232
TI  - Acute graft-versus-host reaction can be aborted by blockade of costimulatory
      molecules.
AB  - Injection of parental lymphocytes into an unirradiated adult F1 host results in
      an acute GVH reaction characterized by immune deficiency, attack on host
      lymphohematopoietic tissues, and repopulation with donor-derived cells. All of
      these events result from the initial activation of donor lymphocytes by host
      alloantigens. Interaction of pairs of host and donor costimulatory molecules, in
      particular CD28/CTLA4 and B7-1/B7-2, play a crucial role in this initial
      activation of donor T cells. We demonstrate here that in vivo treatment of the
      host with high doses of CTLA4-Ig solely during the initial period of donor
      alloactivation can completely abort the subsequent development of GVH reaction.
      Although donor T cells are retained, CTLA4-Ig treatment reduces the initial
      endogenous cytokine production and arrests the subsequent expansion of donor T
      cells, the differentiation of anti-host effectors, and the development of severe
      immune deficiency. This result is consistent with the establishment of host
      specific tolerance in the donor population, while maintaining host immune
      competence.

PMID- 7636233
TI  - Novel dipeptide aldehydes are proteasome inhibitors and block the MHC-I antigen
      processing pathway.
AB  - Class I MHC (MHC-I) molecules present peptides derived from Ag that are processed
      in the cytosol. The proteasome is a multicatalytic protease complex that is
      present in the cytosol and has been implicated in cytosolic Ag processing. Novel
      dipeptide aldehydes were designed, synthesized, and demonstrated to specifically
      inhibit the chymotrypsin-like protease activity of isolated proteasomes, but
      produced relatively little inhibition of cathepsin B, a vacuolar cysteine
      protease. The inhibitors were membrane permeable and inhibited intracellular
      cleavage of a membrane-permeable fluorogenic substrate of the chymotrypsin-like
      proteasome activity. When a model Ag, OVA, was introduced into the cytoplasm of
      M12.B6 murine B cells by electroporation, the proteasome inhibitors blocked its
      processing for subsequent presentation by MHC-I molecules. The inhibitors had
      little effect on class II MHC processing of exogenous Ag. The potencies of
      different inhibitors for blockade of MHC-I Ag processing correlated directly with
      their potencies for inhibition of the chymotrypsin-like proteasome activity. In
      contrast, conventional inhibitors of vacuolar cysteine proteases (e.g., leupeptin
      and benzyloxycarbonyl-Phe-Ala-CHN2) had little effect on MHC-I processing or the
      chymotryspin-like activity of isolated proteasomes. These results directly
      demonstrate that inhibition of proteasome activity blocks MHC-I Ag processing,
      confirming a role for proteasomes in this pathway. Moreover, they suggest that
      the chymotrypsin-like activity of the proteasome may be of major importance to
      the cytosolic processing of at least some Ag.

PMID- 7636234
TI  - Protection from T helper cell-mediated graft-versus-host disease by the presence
      of an MHC class I alloantigen is associated with perturbation of MHC class II
      restricted responses by class I-derived peptides.
AB  - Lethal graft-vs-host disease (GVHD) develops after transfer of CTL-depleted
      spleen and bone marrow cells from C57BL/6 (B6) mice to irradiated MHC class II
      disparate (B6xbm12)F1 recipients. Onset of lethal GVHD is significantly delayed
      in (bm1xbm12)F1 recipients of the same donor inoculum despite the additional MHC
      class I disparity (H-2Kbm1). To investigate the basis of this protective effect,
      hybridomas were generated from T cells activated in vivo during GVHD in both
      strain combinations. T cells from B6-->(B6xbm12)F1 mice generated a significantly
      higher frequency of B6.C-H-2bm12 (bm12)-specific T hybridomas (110/178, 62%) than
      T cells from B6-->(bm1xbm12)F1 mice (102/218, 47%). Some bm12-specific T
      hydridomas exhibited lesser responses to (bm1xbm12)F1 than to (B6xbm12)F1 APC.
      Moreover, bm1 peptides spanning a 14-amino acid region that includes the three
      amino acids that differ from H-2Kb were found to inhibit responses of some bm12
      specific T hybridomas and to decrease significantly responses of splenic B6 CD4+
      T cells to bm12 APC. Notably, the frequency of bm12-reactive hybridomas
      susceptible to inhibition by bm1 peptides generated from B6-->(B6xbm12)F1 mice
      was significantly greater than that generated from B6-->(bm1xbm12)F1 mice.
      Additional analysis using L cell transfectants indicated that hybridomas
      responding to the bm12 mutation at position 70 alone were rarely inhibited by bm1
      peptides. The data indicate that expression of bm1-derived peptides can influence
      the frequency and specificity of alloreactive CD4+ T cells stimulated in vivo and
      thus may alter the course of GVHD.

PMID- 7636235
TI  - Glucocorticoid-mediated regulation of protein phosphorylation in primary human T
      cells. Evidence for induction of phosphatase activity.
AB  - Glucocorticoid hormones (GC) have profound effects on the development and
      homeostasis of the immune system. In this communication we present evidence that
      GC regulate Ca(2+)-mediated pathways of T cell activation by a mechanism that
      involves abrogation of the autophosphorylation of the multifunctional
      Ca2+/calmodulin kinase (CaM kinase II) and induction of protein phosphatase
      activity. Primary human T cells were stimulated with the combination of ionomycin
      and phorbol ester in the presence or absence of dexamethasone (Dex) (10(-6)-10(
      12) M). Stimulation of T cells resulted in a rapid activation of CaM kinase II
      and protein kinase C (PKC) activity as determined by the phosphorylation of
      synthetic peptide substrates recognized by these enzymes. Dex inhibited the
      activity of CaM kinase II but not PKC activity in a dose-dependent fashion
      (minimum effective dose 10(-10) M). Stimulation of 32P-labeled T cells induced a
      rapid increase in the phosphorylation level of CaM kinase II which was inhibited
      by Dex. The inhibitory effect of Dex on this enzyme was fully reversed in the
      presence of the phosphatase inhibitor okadaic acid (250 nM) or RU 486, a
      glucocorticoid antagonist. These results suggest that GC inhibit the activation
      of CaM kinase during T cell activation through a mechanism that involves both the
      GC receptor and protein phosphatases 2A and/or 1. Inhibition of protein
      phosphorylation through the induction of protein phosphatase activity may
      represent a novel mechanism for the diverse effects of GC on eukaryotic cells.

PMID- 7636236
TI  - Lysosome-associated membrane protein-1-mediated targeting of the HIV-1 envelope
      protein to an endosomal/lysosomal compartment enhances its presentation to MHC
      class II-restricted T cells.
AB  - A subset of endogenously synthesized Ags can be processed for class II-restricted
      presentation, probably through multiple mechanisms. Processing of exogenous Ags
      for class II-restricted presentation appears to occur in unique endosomal
      processing compartments with lysosomal characteristics including the presence of
      the lysosomal membrane protein LAMP-1. Therefore, we attempted to enhance the
      efficiency of class II-restricted presentation of an endogenous Ag, the HIV-1
      envelope (env) protein, by specifically targeting the Ag to class II processing
      compartments through the pathway followed by LAMP-1. Because the env protein
      associates tightly with CD4 shortly after synthesis, we first targeted the env
      protein using a chimeric CD4 protein consisting of the extracellular domain of
      CD4 and the transmembrane and cytoplasmic domains of LAMP-1. When co-expressed
      with this chimeric protein, the env protein was efficiently localized to lysosome
      like compartments. Enhanced stimulation of env-specific CD4+ T cell clones by APC
      expressing the env protein and the CD4-LAMP-1 chimera was readily demonstrated in
      both cytotoxicity assays and proliferation assays. We also targeted the env
      protein directly as a chimeric protein consisting of the extracellular domain of
      the env protein and the transmembrane and cytoplasmic domains of LAMP-1. The
      proliferative response of env-specific CD4+ T cell clones to the env-LAMP-1
      chimera was greatly enhanced compared with wild-type env protein, especially when
      limiting numbers of stimulator cells were used. The enhanced stimulatory capacity
      of APC expressing LAMP-1-targeted Ags has important implications for vaccine
      design.

PMID- 7636237
TI  - Differential human T cell-dependent B cell differentiation induced by
      staphylococcal superantigens (SAg). Regulatory role for SAg-dependent B cell
      cytolysis.
AB  - Microbial superantigens (SAg), by virtue of their binding to TCR V beta elements
      and to class II MHC molecules on accessory cells, trigger T cell proliferation in
      a dose-dependent fashion. In contrast, SAg-induced T cell-dependent B cell
      differentiation occurs only at SAg concentrations that are orders of magnitude
      lower that those required for optimal mitogenesis (low-dose SAg). At optimal
      mitogenic doses (high-dose SAg), SAg-driven B cell differentiation does not
      ensue. In this report, we demonstrate that this dichotomy in SAg-driven B cell
      differentiation is due to the active inhibition of B cell differentiation by high
      dose SAg. Such inhibition is not reversed by feeding cultures with fresh medium,
      with conditioned media, or with IL2 +/- IL4, and impaired B cell differentiation
      is observed in cultures containing purified T cells or CD4+ T cells + B cells, as
      well as in PBMC cultures. Although preincubation of either T cells or B cells
      with high-dose SAg impairs subsequent SAg-induced B cell differentiation, high
      dose SAg is not toxic per se, since high-dose SAg does promote vigorous B cell
      differentiation in cultures of mitomycin C-treated T cells + B cells and does not
      inhibit T cell-independent B cell differentiation. No correlation exists between
      SAg-induced B cell surface expression of CTLA4 ligand and generation of Ig
      secreting cells, but the dose of SAg does correlate with T cell-mediated SAg
      dependent cytolysis of transformed B cell targets or autologous nontransformed
      activated B cell targets. B cell recovery from cultures stimulated with high-dose
      SAg is lower than that from cultures stimulated with low-dose SAg, whereas B cell
      apoptosis is greater in the former cultures than that in the latter cultures. T
      cells stimulated with high-dose SAg do not inhibit differentiation of activated B
      cells in the absence of physical contact between the T cells and the target B
      cells, supporting the notion of direct killing of activated B cells by T cells.
      The ability of low doses of SAg to promote B cell differentiation without
      generating biologically meaningful cytolytic activity and the ability of higher
      doses of SAg to modulate Ig production may have important pathogenetic and
      therapeutic ramifications for certain autoimmune disorders, such as systemic
      lupus erythematosus.

PMID- 7636238
TI  - Invariant chain-independent antigen presentation depends primarily upon the pool
      of newly synthesized MHC class II molecules.
AB  - During biosynthesis, MHC class II molecules are diverted to endocytic
      compartments in which they bind antigenic peptides to be displayed on the
      surfaces of APC. For many Ags, the efficiency of class II presentation is
      enhanced by the intracellular association of class II with invariant chain (li),
      consistent with a role for newly synthesized class II molecules in Ag
      presentation. For a subset of Ags, however, efficient presentation does not
      require li. These Ags may also be bound by class II molecules en route to the
      cell surface. Alternatively, li-independent Ag presentation may utilize a pool of
      preexisting class II molecules that may gain access to endosomes following
      internalization from the cell surface. To examine the role of newly synthesized
      class II in the presentation of the li-independent Ag, RNase, we placed class II
      biosynthesis under the translational control of an iron response element.
      Chelation of iron from the media resulted in efficient diminution of class II
      synthesis and a marked decrease in the efficiency of RNase presentation. When
      compared with other cells expressing varying amounts of class II, we found that
      the ability to present RNase correlates with the level of class II biosynthesis
      and not with the level of class II surface expression. Because these cells
      internalize class II at a significant rate, we conclude that even in the absence
      of li, class II molecules can reach endocytic compartments containing antigenic
      peptides and they do so on their biosynthetic pathway.

PMID- 7636239
TI  - Variable influence of MHC polymorphism on the recognition of bacterial
      superantigens by T cells.
AB  - Superantigen recognition by some T cells is strongly influenced by polymorphic
      residues of the MHC class II molecule, suggesting that the TCR contacts the class
      II molecule during superantigen engagement. However, the degree of MHC preference
      varies with V beta expression. For example, the recognition of staphylococcal
      enterotoxin B (SEB) by murine V beta 14+ T cell hybridomas is strongly influenced
      by MHC polymorphism, whereas the recognition of SEB by V beta 8.2+ hybridomas
      appears to be independent of MHC polymorphism. One possible explanation for this
      difference is that V beta 14+ TCR may have a lower avidity for SEB such that the
      stability of the TCR/SEB/MHC complex is more strongly influenced by potential
      TCR/MHC interactions. To investigate this possibility, we examined the MHC
      preference of SEB recognition by murine V beta 8.2+/CD4+ T cell hybridomas in
      which we altered the strength of SEB recognition. First, we compared the
      recognition of wild-type SEB and mutant SEB, which only weakly activates T cells.
      Second, we compared recognition of SEB presented by I-E and I-A molecules, which
      differ in their affinity for SEB. In both cases, the degree of MHC preference was
      significantly increased when the strength of SEB recognition was reduced.
      Furthermore, we used mutant MHC class II molecules to show that the degree of MHC
      preference was controlled by residues of the class II molecule predicted to
      interact with the TCR during SEB recognition. Taken together, these data support
      the idea that there is a TCR/MHC interaction during SEB recognition, and the
      influence of this interaction varies with the overall avidity of the TCR/SEB/MHC
      complex.

PMID- 7636240
TI  - Glucocorticoids accelerate anti-T cell receptor-induced T cell growth.
AB  - To study steroid regulation of cell-mediated immunity, we used anti-TCR
      stimulated rat splenic lymphocyte mitogenesis as our experimental paradigm.
      Surprisingly, we found that the principal glucocorticoid of the rat,
      corticosterone (CORT), potently enhanced anti-TCR-induced lymphocyte
      proliferation after 2 to 3 days in culture, followed by inhibited cell growth
      after 5 to 7 days. Thus, glucocorticoids appeared to accelerate anti-TCR-induced
      lymphocyte mitogenesis. This effect occurred at physiologic concentrations (50
      1000 nM), which are known to be released in vivo after an immune challenge.
      Kinetic experiments showed that CORT had to be present within 60 min after the
      initiation of TCR activation to produce maximal enhancing effects; a delay of 2 h
      or more left CORT ineffective. The lymphocytes incubated with CORT may have an
      increased sensitivity to IL-2 because 1) CORT suppressed IL-2 production
      throughout the culture period, and 2) an anti-IL-2R mAb completely blocked both
      control and CORT-treated anti-TCR-induced lymphocyte proliferation. Although the
      IL-2R alpha- and beta-chain mRNA concentrations were not altered in CORT-treated
      splenocyte cultures, we observed by FACS analysis an increased expression of the
      IL-2R alpha-chain on CORT-treated TCR alpha beta + and CD4+ T cells after 48 to
      72 h of culture, suggesting an increased sensitivity of these T cells to IL-2
      during the phase of enhanced proliferation. These results demonstrate a clear
      distinction between the enhancing effects of glucocorticoids on anti-TCR-induced
      lymphocyte proliferation and their well known inhibitory actions. Thus, the
      present study expands the regulatory role of glucocorticoids in cellular
      immunity, adding a novel effective stimulatory component to their inhibitory
      properties.

PMID- 7636241
TI  - Identification of heavy chain residues in a humanized anti-CD3 antibody important
      for efficient antigen binding and T cell activation.
AB  - A previously identified humanized anti-CD3 Ab variant, v9, binds T cells with >
      100-fold higher efficiency than the original variant, v1, and almost as
      efficiently as a chimeric molecule containing corresponding murine variable
      domains. Variants v1 and v9 differ at six positions in the H chain second CDR.
      Here a mutational analysis was used to identify which of these six replacements
      are primarily responsible for the difference in binding efficiency. These anti
      CD3 variants were used to probe the relationship between Ag binding efficiency
      and potency in stimulating T cell proliferation. The human to mouse mutations
      T57S and V63F increase the binding efficiency of variant v1 for T cells by 8- and
      12-fold, respectively, and together in variant M18 enhance binding by 26-fold to
      within 4-fold of variant v9. A framework mutation, 169L, was identified that
      enhances the binding of variants v1 and M18 by 14- and 3-fold, respectively. The
      Ag binding efficiencies of anti-CD3 variants correlate directly with their
      potencies in stimulating the proliferative activity of both resting human PBMC
      and IL-2-activated human T lymphocytes. Humanized variant v9 is equipotent to the
      murine parent Ab in stimulating ATL activity. PBMC activated by variants v1 and
      v9 IgG in a short term culture are equally cytotoxic against human breast
      carcinoma cells. Thus, high efficiency Ag binding by anti-CD3 variants is
      important for stimulating efficient T cell proliferation, but not cytotoxicity,
      in vitro.

PMID- 7636242
TI  - The Ig heavy chain switch region is a hotspot for insertion of transfected DNA.
AB  - The Ig heavy chain class switch usually occurs by breaking and rejoining DNA in
      the switch (S) regions, which consist of tandemly repeated sequences 5' of the
      constant region exons. Various studies have suggested that S DNA can also
      recombine with non-S sequences. To measure the frequency of such recombination
      events, the hybridoma cell line igm692, a deletion mutant that lacks the C mu 1
      and C mu 2 exons and the 3' end of the S mu region, was transfected with a
      fragment bearing the C mu 1-2 exons, but no S mu DNA. Insertion of this fragment
      into the residual VDJ-C mu intron of igm692 can restore a functional mu gene,
      yielding a transformant that is detected as a plaque-forming cell (PFC). PFC
      comprise approximately 8 x 10(-7) of the surviving transfected cells. In 10 of 12
      PFCs, the C mu 1-2 fragment inserted into the 2.5-kb residual S mu region,
      whereas insertion in two cases occurred in the 3.5-kb segment 5' of S mu. Using a
      PCR assay to measure the frequency of insertion of the transferred fragment
      elsewhere in the hybridoma genome, we found that approximately 9% of the
      surviving transfected cells had stably acquired the C mu 1-2 fragment. These
      results indicate that the S mu region is approximately 100-fold more
      recombinogenic than the average genomic site, and approximately 7-fold more
      recombinogenic than the non-S mu segment of the residual VDJ-C mu, i.e., the S mu
      region is a hotspot for insertion of transfected DNA.

PMID- 7636243
TI  - Differential stability of HLA-DR alleles independent of endogenous peptides.
AB  - Purified HLA DRB1*0101 was shown to be inherently more stable to dissociation
      than DRB1*0401. The residues responsible for the differential stability were
      defined by constructing hybrid molecules, which contained a small number of
      residues from DRB1*0101 substituted into the framework of DRB1*0401. One of the
      hybrid molecules, containing six substituted amino acids, was as stable as
      DRB1*0101, but exhibited the binding specificity of DRB1*0401. This result
      indicated that the differential stability between the alleles arose from
      structural differences, and was not due solely to varying populations of
      endogenous peptides.

PMID- 7636244
TI  - Differential regulation of alternative 3' splicing of epsilon messenger RNA
      variants.
AB  - Alternative 3' splicing of the one active human epsilon heavy chain gene results
      in variants of epsilon mRNA encoding distinct IgE proteins. The same relative
      amounts of these epsilon mRNA variants were produced by non-atopic donor B cells
      when driven in a variety of T-dependent or T-independent systems. The most
      abundant variants were those for classic secreted epsilon a novel secreted form
      (CH4-M2"). In contrast, cells from subjects with high levels of serum IgE
      secondary to parasitic infection or atopy spontaneously produced higher relative
      levels of the CH4-M2' epsilon mRNA variant, lower relative amounts of both the
      membrane and CH4-M2" secreted variants, and very low levels of the CH4'-CH5
      variant. The existence of and corresponding changes in levels of the CH4-M2'
      encoded secreted protein were demonstrated. IL-10 induced this same differential
      expression of epsilon splice variants in vitro when used to costimulate IL-4 plus
      CD40-driven B cells and could differentially enhance the production of CH4-M2'
      protein by established IgE-secreting cell lines. Inhibition of IgE by cross
      linking the low affinity IgE receptor (CD23) decreased the levels of epsilon mRNA
      and resulted in a distinct pattern of epsilon mRNA characterized by a dramatic
      decrease in CH4-M2' splice variant. IL-6, IL-2, or IFN-gamma did not change the
      epsilon mRNA pattern. Overall, the absolute and relative amounts of the different
      epsilon mRNA splice variants produced appear to be controlled in a
      differentiation-related fashion.

PMID- 7636245
TI  - Expression cloning and chromosomal mapping of the leukocyte activation antigen
      CD97, a new seven-span transmembrane molecule of the secretion receptor
      superfamily with an unusual extracellular domain.
AB  - CD97 is a monomeric glycoprotein of 75 to 85 kDa that is induced rapidly on the
      surface of most leukocytes upon activation. We herein report the isolation of a
      cDNA encoding human CD97 by expression cloning in COS cells. The 3-kb cDNA clone
      encodes a mature polypeptide chain of 722 amino acids with a predicted molecular
      mass of 79 kDa. Within the C-terminal part of the protein, a region with seven
      hydrophobic segments was identified, suggesting that CD97 is a seven-span
      transmembrane molecule. Sequence comparison indicates that CD97 is the first
      leukocyte Ag in a recently described superfamily that includes the receptors for
      secretin, calcitonin, and other mammalian and insect peptide hormones. Different
      from these receptors, CD97 has an extended extracellular region of 433 amino
      acids that possesses three N-terminal epidermal growth factor-like domains, two
      of them with a calcium-binding site, and a single Arg-Gly-Asp (RGD) motif. The
      existence of structural elements characteristic for extracellular matrix proteins
      in a seven-span transmembrane molecule makes CD97 a receptor potentially involved
      in both adhesion and signaling processes early after leukocyte activation. The
      gene encoding CD97 is localized on chromosome 19 (19p13.12-13.2).

PMID- 7636246
TI  - Structural requirements of peptide and MHC for DR(alpha, beta 1*0401)-restricted
      T cell antigen recognition.
AB  - We identified functionally important regions of the DR(alpha, beta 1*0401)
      peptide binding site and present a model of bound peptide. DR(alpha, beta 1*0401)
      restricted T cell recognition and peptide binding of Mycobacterium leprae (ML)
      peptide 38-50 and overlapping peptides from the 18-kDa heat-shock protein were
      analyzed. ML38-50 is unusual in its restricted binding pattern, binding to only
      one of five DR4 subtypes and no other DR molecules tested. Amino acid
      substitutions were introduced into ML38-50 and the DR(alpha, beta 1*0401) peptide
      binding site at positions likely to influence peptide-MHC or peptide- or MHC-TCR
      interactions. Peptide binding, T cell proliferation, and computer modeling
      studies suggest that residues 39F, 42E, and 44D of ML38-50 interact with pockets
      1, 4, and 6, respectively, of the peptide binding site. Only DR(alpha, beta
      1*0401) substitutions at residues in pockets 4 or 7 prevented binding of ML38-50,
      while multiple substitutions at other positions negatively affected its T cell
      recognition. In contrast, T cell recognition of some high affinity ML peptides
      that overlapped ML38-50, and contained N-terminal extensions, was only abolished
      with pocket 4 substitutions. An inverse correlation of peptide affinity for
      DR(alpha, beta 1*0401) with negative effects of MHC substitutions on T cell
      recognition of the overlapping ML peptides was observed. Thus, some regions, such
      as pocket 4, dominantly influence T cell recognition of multiple DR(alpha, beta
      1*0401)-binding peptides. However, each DR(alpha, beta 1*0401)-binding peptide
      appears to have unique properties that determine the outcome of its MHC-peptide
      interactions and the relative importance of other polymorphic pockets.

PMID- 7636247
TI  - Isolation of Xenopus LMP-7 homologues. Striking allelic diversity and linkage to
      MHC.
AB  - The mammalian low molecular mass protein-7 (LMP-7) gene resides in the class II
      region of the MHC, and its product is most probably involved, as a component of a
      proteasome, in the processing of Ags to be presented by the MHC class I
      molecules. To elucidate the evolution of the LMP-7 gene at both the primary
      structure and genetic levels, we isolated LMP-7 cDNA clones from amphibian
      Xenopus laevis, which last shared a common ancestor with mammals 350 x 10(6)
      years ago. Two distinctive clones, showing an 85% predicted amino acid sequence
      identity with each other and 69 to 72% identity with human and mouse LMP-7, were
      identified from a liver cDNA library of outbred frogs and named XeLMP-7A and
      XeLMP-7B. XeLMP-7A- and XeLMP-7B-specific probes were used to detect the
      corresponding genes by using partially inbred frogs with known MHC haplotypes.
      DNA of the g and j haplotypes hybridized with the XeLMP-7A probe, whereas the f
      and r haplotype DNA hybridized with the XeLMP-7B probe. These hybridization
      patterns cosegregated with the MHC haplotypes among offspring of an f/f x f/g
      cross, and one recombinant revealed that the LMP-7 gene is linked more closely to
      class II than to class I or class III genes. Taken together, the data indicate
      that XeLMP-7A and XeLMP-7B are highly diverse alleles at a single locus in the
      frog MHC. The great allelic diversity can be explained either by coselection with
      particular class I alleles or by differential silencing of MHC genes in the
      polyploid X. laevis.

PMID- 7636248
TI  - Activation of IL-2 receptor alpha-chain gene by individual members of the rel
      oncogene family in association with serum response factor.
AB  - Expression of the IL-2R alpha gene is regulated by members of the c-Rel/NF-kappa
      B family of transcription factors binding to the kappa B site in the promoter.
      Previous work has not defined the role of individual members of the c-Rel family
      in the activation of the IL-2R alpha gene. Using the COS cell system, we were
      able to reconstitute the regulation of the IL-2R alpha promoter by expressing
      cloned Rel family members with serum response factor (SRF). We found that c-rel
      alone activated the IL-2R alpha promoter only weakly but worked with the p50
      subunit of NF-kappa B (NFKB1) to give a higher level of expression. We showed
      that c-rel heterodimerizes with p50 and the amount of this heterodimer correlated
      with the level of IL-2R alpha gene expression. Our results provide evidence that
      c-rel/p50 heterodimers activate gene expression in the context of a cellular
      promoter. We show that c-rel or p65 can cooperate with SRF in the activation of
      this promoter and the transactivation by c-rel with SRF was enhanced by p50.
      Synergistic activation required both kappa B and CArG sites, and binding studies
      show that these adjacent sites can be occupied simultaneously. The
      transactivation observed with cloned transcription factors mimics the physiologic
      induction of the IL-2R alpha gene since multiple sequence elements cooperate to
      give gene activation. The data support the model that c-rel/p50 or p65 can
      cooperate with SRF to specifically target the expression of the IL-2R alpha gene
      in activated T cells.

PMID- 7636249
TI  - Diversity of T cell receptor delta-chain cDNA in the thymus of a one-month-old
      pig.
AB  - Pig TCR delta-chain cDNA sequences were obtained from the anchored PCR products
      of the reverse-transcribed RNA from the thymus of a 1-mo-old germfree pig. Among
      43 sequences analyzed, 4 different J delta sequences were found, and in the cDNA
      sequences of rearranged V-D-J junctional regions, three putative D delta
      sequences were assigned. Also, the V delta region sequences were grouped into
      five families. One family, V delta 1, consisted of a large number of members and
      the other families consisted of limited members as determined by cDNA sequences
      as well as genomic Southern blots. Using PCR, V delta 1 gene segments were also
      obtained from liver genomic DNA of the same individual pig. Thirty-one distinct
      sequences were found for the V delta 1 family including the sequences obtained
      from both the thymic RNA and the PCR product of liver DNA. All the V delta 1
      genes were found to be associated with almost identical leader gene sequences.
      The amino acid sequences of the complimentarity-determining region 3 coded by the
      V-D-J joints gave long and variable lengths with a high content of tryptophan and
      charged amino acids. The length of the complimentarity-determining region 3 in
      the porcine TCR delta-chain supports the idea that TCR delta-chain is designed to
      see Ags directly similar to the Ig heavy chain. Data presented from this study
      shows that the porcine TCR delta-chain has extensive V region diversity as well
      as junctional diversity. The combination of these two creates a level of
      diversity that is the highest of any lymphocyte Ag receptor studied so far.

PMID- 7636250
TI  - Affinity maturation of the BR96 anti-carcinoma antibody by codon-based
      mutagenesis.
AB  - We have increased up to 65-fold the avidity of BR96, a mAb recognizing Lewis Y
      (Le(y))-related Ags expressed on the surface of many human carcinomas. Libraries
      of mutations in the complementarity-determining regions (CDRs) of BR96 were
      constructed in an M13 phage Fab expression vector by codon-based mutagenesis, a
      method that efficiently introduces large numbers and potentially all combinations
      of amino acid substitutions. Two mutants that improved the affinity of BR96 to
      tumor Ag were identified by screening the libraries on carcinoma cell lines. One
      mutant, M1, at position 97 (Asp to Ala) in CDR3 of the heavy chain, resulted in
      an 8- to 10-fold improvement in Ag binding, as assessed by ELISA. A second
      mutant, M2, at position 53 (Gly to Asp) in CDR2 of VH increased binding three- to
      fivefold. When these mutations were combined, the resulting Fab M3 was improved
      approximately 30-fold. An additional library was constructed in CDR1 of M1. M4, a
      mutation with three amino acid substitutions in CDR1, was isolated by screening
      the library with an enzyme conjugate of synthetic Le(y) tetrasaccharide (sLe(y)).
      This mutant improved BR96 Fab affinity to sLe(y) an estimated 15- to 20-fold by
      ELISA, and 14-fold as measured by surface plasmon resonance. The M4 IgG had 65
      fold improved avidity to sLe(y) relative to the BR96 IgG. The mutants will be
      useful for comparison of the efficacy of Abs with different affinities for
      delivery of cytotoxic agents to tumor cells.

PMID- 7636251
TI  - Differences in the shedding of soluble TNF receptors between endotoxin-sensitive
      and endotoxin-resistant mice in response to lipopolysaccharide or live bacterial
      challenge.
AB  - TNF-alpha plays a pivotal role in the pathogenesis of septic shock. It exerts its
      effects by binding two cell surface receptors, designated TNF-R I and II, also
      referred to as the p55 and p75 receptors, respectively. TNF-Rs are transmembrane
      proteins, which on cleavage of their extracellular domains, result in the release
      of soluble fragments (sTNF-R). sTNF-R levels increase markedly during infection,
      and may serve to modulate TNF-alpha bioactivity. The mechanisms regulating this
      process are uncertain. To investigate this, we measured sTNF-R release in
      endotoxin-sensitive C3H/HeN and endotoxin-resistant C3H/HeJ mice given LPS or
      live Gram-negative bacteria. In C3H/HeN mice, there was a rapid early response
      during the first 4 h, and a second peak at 8 h, particularly noticeable in the
      case of the p75 receptor. Prior administration of neutralizing Abs to TNF-alpha
      or IFN-gamma had no effect on receptor shedding. Surprisingly, C3H/HeJ mice also
      responded to both bacterial challenge and to LPS by shedding sTNF-R; the
      magnitude and duration of the early response was not substantially different from
      C3H/HeN mice, although the second peak was absent. Peritoneal macrophages from
      C3H/HeN mice responded promptly (5 h) when stimulated with LPS in vitro, and by
      22 h levels had increased five- to 10-fold. In contrast, cells from C3H/HeJ mice
      demonstrated only a very modest response at 22 h following maximal stimulation.
      The data suggest that there may be at least two separately regulated pathways
      that control sTNF-R shedding in these mice.

PMID- 7636252
TI  - Endogenously produced IL-12 is required for the induction of protective T cells
      during Mycobacterium avium infections in mice.
AB  - Immunity to Mycobacterium avium depends on the induction of protective CD4+ T
      cells. In mice, M. avium induces a Th1 response leading to protective immunity
      dependent on IFN-gamma and TNF. In this study, we analyzed whether endogenously
      produced IL-12 was involved in the generation of such protective T cells. We
      found that the neutralization of IL-12 with the administration of specific mAbs
      throughout the course of the infection led to the inability of BALB/c mice to
      control the infection by M. avium strain 2447. On the contrary, the late
      neutralization of IL-12, with the administration of the mAb starting only at the
      third week of infection, did not affect the growth of M. avium. The
      neutralization of IL-12 blocked the induction of protective T cells detected upon
      adoptive transfer to sublethally irradiated recipient mice. The neutralization of
      IL-12 in the recipient mice did not affect the protective activity of immune
      cells, showing that IL-12 is involved mainly in the induction, and not the
      expression, of acquired cell-mediated immunity. IL-12 was also shown to be
      required for a T cell-independent pathway of resistance present in T cell
      deficient severe combined immunodeficient (SCID) mice. Finally, animals whose IL
      12 was blocked expressed heightened levels of IL-4 and IL-10 message and reduced
      expression of IFN-gamma as compared with control mice.

PMID- 7636253
TI  - Role of IL-4 and IFN-gamma in modulation of immunity to Borrelia burgdorferi in
      mice.
AB  - Because T cells appear to modulate the severity of murine Borrelia burgdorferi
      infections, we decided to examine the possible involvement of T cell-associated
      cytokines in disease outcome. Comparison of in vitro B. burgdorferi Ag-induced
      cytokine production in disease-susceptible and -resistant strains revealed
      striking differences; spleen cells from susceptible C3H mice produced
      significantly higher levels of IL-2 and IFN-gamma and lower levels of IL-4 than
      spleen cells from resistant BALB/c mice. Lymph node responses were even more
      divergent, with C3H mice producing high levels of IFN-gamma, and BALB/c mice
      producing little or none. This apparent Th1/Th2 cytokine imbalance was also
      reflected in vivo, since serum from C3H had significantly higher levels of B.
      burgdorferi-specific IgG2a Ab and lower levels of IgG1 Ab than serum from BALB/c
      mice. In vivo studies confirmed the importance of IL-4 in early control of
      spirochete growth, since treatment of either strain with neutralizing anti-IL-4
      mAb led to increased joint swelling and higher spirochete burdens in joints
      compared with those in control mAb-treated mice. In contrast, IFN-gamma may
      hinder early control of spirochete growth in susceptible C3H mice, since
      treatment of mice with neutralizing anti-IFN-gamma mAb reduced both joint
      swelling and joint spirochete burdens compared with those in control mAb-treated
      mice. These studies indicate opposing roles for IL-4 and IFN-gamma in the
      modulation of spirochete growth and disease development in B. burgdorferi
      infected mice and suggest that differential cytokine production early in
      infection may contribute to strain-related differences in susceptibility.

PMID- 7636254
TI  - Mucoid Pseudomonas aeruginosa growing in a biofilm in vitro are killed by opsonic
      antibodies to the mucoid exopolysaccharide capsule but not by antibodies produced
      during chronic lung infection in cystic fibrosis patients.
AB  - Serum opsonophagocytic-killing titers often indicate the level of immune
      resistance to bacterial pathogens, yet in almost all cystic fibrosis (CF)
      patients that have chronic lung infections with mucoid Pseudomonas aeruginosa,
      high titers of opsonic-killing Abs can be measured and the infectious pathology
      still progresses through pulmonary failure and death. This anomalous finding may
      be due to the use of suspended cells of P. aeruginosa to evaluate phagocytic
      killing, whereas in the lungs of CF patients the organisms grow in a microcolony
      or biofilm, encased in mucoid exopolysaccharide (MEP, also called alginate). To
      determine whether the microcolony mode of growth contributes to bacterial
      resistance to host defenses, we evaluated opsonophagocytic killing of mucoid P.
      aeruginosa growing in a biofilm. Abs from infected CF patients were poorly able
      to mediate opsonic killing of biofilm, but not suspended, mucoid P. aeruginosa
      cells. Bacterial resistance to killing could be overcome by disruption of the
      biofilm layer with an enzyme that degrades MEP. Chronically infected CF patients
      also fail to produce opsonic-killing Abs specific to MEP, and when these Abs were
      evaluated in sera of older, noninfected CF patients and humans vaccinated with
      MEP, comparable killing of P. aeruginosa in biofilms and suspensions was
      obtained. In this case, C3 was deposited onto the MEP layer and could be
      visualized by fluorescence microscopy deposited throughout the biofilm. We
      conclude that opsonic Abs made by CF patients in response to chronic infection
      are ineffective at mediating phagocytic killing and elimination of bacterial
      cells growing as microcolonies in their lungs.

PMID- 7636255
TI  - Complexity of the cytokine and antibody response elicited by immunizing mice with
      Plasmodium yoelii circumsporozoite protein plasmid DNA.
AB  - The number, type, and location of cytokine- and Ab-secreting cells activated in
      mice immunized and boosted with plasmid DNA encoding the circumsporozoite protein
      of the malarial parasite Plasmodium yoelii (PyCSP) were monitored. The initial
      humoral response was localized to the draining lymph nodes and was characterized
      by production of IgG1 anti-PyCSP Abs and the Th2 cytokine IL-4. In contrast, the
      secondary response was dominated by IFN-gamma production (a Th1 cytokine) and the
      secretion of IgG2a anti-PyCSP Abs in the spleen. PyCSP DNA and mRNA were detected
      only in the quadriceps muscles (sites of plasmid injection), yet these sites
      lacked either cytokine- or Ab-secreting cells. These findings indicate that
      circulating lymphocytes encounter plasmid-encoded Ag in the muscle bed, initiate
      a humoral response in the draining lymph nodes, and then seed distal lymphoid
      organs. Profound differences were observed between the primary and secondary
      immune responses induced by plasmid immunization, which may influence vaccine
      efficacy.

PMID- 7636256
TI  - Bacterial infection of the testis leading to autoaggressive immunity triggers
      apparently opposed responses of alpha beta and gamma delta T cells.
AB  - The mechanisms that lead to the breakdown of self-tolerance and testis-specific
      immune reactivity in the murine orchitis model are understood only in part. We
      investigated the histopathologic and immunologic consequences of a unilateral
      bacterial (Listeria monocytogenes) infection of the testis. Both infected and
      contralateral sides of this bilateral organ suffered severe inflammatory
      responses despite a conspicuous absence of bacteria in the contralateral tissue.
      Also, in both testicles, T cell populations increased, involving both alpha beta
      and gamma delta T cell subsets. Concomitant with the bilateral orchitis, testis
      specific delayed type hypersensitivity and Ab responses developed. Ab depletion
      experiments indicated that in this orchitis model, as in others, alpha beta T
      cells are initiators of the autoaggressive reactivity. In contrast, Ab depletion
      of gamma delta T cells accelerated the inflammatory response in both testicles,
      suggesting a regulatory role for this type of T cells in both infection-induced
      and autoimmune orchitis.

PMID- 7636257
TI  - Mice with the xid B cell defect are less susceptible to developing Staphylococcus
      aureus-induced arthritis.
AB  - To investigate the role of B cells in the development of experimental
      Staphylococcus aureus-induced arthritis, we used X-linked immunodeficiency (xid)
      mice that carry a Bruton's tyrosine kinase mutation affecting the function of B
      cells. NFR/N.xid and congenic NFR/N mice were inoculated i.v. with a toxic
      syndrome toxin-1 producing S. aureus LS-1 strain. B cell-deficient NFR/N.xid mice
      developed less frequent (p < 0.01) and less severe (p < 0.01) arthritis than
      NFR/N mice did. These clinical findings were corroborated by histopathologic
      evaluation, indicating that NFR/N.xid mice had significantly lower (p < 0.01)
      erosivity of the disease. Interestingly, infected NFR/N.xid mice showed decreased
      bacterial burden in blood, joints, and other organs compared with the control
      mice. Serologic studies displayed poor B cell responses to staphylococcal cell
      walls, toxic shock syndrome toxin-1, and ssDNA, accompanied by a low level of Igs
      in infected NFR/N.xid mice. More importantly, xid defect affected cytokine
      profile. The in vitro experiments showed that the lymphocytes from NFR/N.xid mice
      had low IL-6, but high IFN-gamma production upon stimulation with staphylococcal
      cell walls compared with NFR/N mice. Furthermore, the in situ hybridization
      technique revealed the relative increase of IFN-gamma, but marked decrease of IL
      1 beta mRNA expression in spleens of infected NFR/N.xid mice. No significant
      difference in IL-4, IL-10, and TNF-alpha mRNA expression was found between both
      strains. Our findings demonstrate that B cells may, directly or indirectly,
      contribute to the pathogenesis of septic arthritis. The results indicate that
      increased IFN-gamma production along with low IL-6 and IL-1 beta synthesis found
      in xid mice may provide a more favorable outcome of S. aureus arthritis.

PMID- 7636258
TI  - Transforming growth factor-beta stimulates arginase activity in macrophages.
      Implications for the regulation of macrophage cytotoxicity.
AB  - Macrophage arginine metabolism via nitric oxide (NO) synthase and arginase
      pathways reduces and enhances tumor cell proliferation, respectively.
      Transforming growth factor-beta (TGF-beta) has been shown to down-regulate the NO
      synthase pathway. The present study describes the effect of TGF-beta on the
      arginase pathway. TGF-beta up-regulated arginase activity in rat peritoneal
      macrophages as assessed by measuring the generation of [14C]urea from [14C]-L
      arginine in the presence of NG-monomethyl-L-arginine (L-NMMA). The stimulation,
      which reached fivefold after a 48-h exposure of macrophages to 10 ng/ml TGF-beta,
      was due to reduction in Km value of arginase. TGF-beta-induced up-regulation of
      arginase activity led to the release of more polyamines, mainly putrescine. The
      role of this up-regulation on macrophage cytotoxicity toward L-929 tumor cells
      was analyzed in coculture experiments. Macrophages blunted DNA synthesis by L-929
      cells as assessed by measuring the incorporation of [3H]TdR into the cells and
      the proportion of cells in the G2 phase. Addition of TGF-beta in the presence of
      L-NMMA permitted L-929 cells cocultured with macrophages to resume DNA synthesis.
      The mechanism responsible for this restoration was the up-regulation of arginase
      activity rather than the down-regulation of NO synthase activity since TGF-beta
      in the presence of L-NMMA failed to further reduce NO synthase activity whereas
      it still enhanced arginase activity; synthetic putrescine (1-10 microM) also
      blunted macrophage cytotoxicity toward L-929 cells. This is the first evidence
      that TGF-beta up-regulates arginase activity in macrophages and, hence, limits
      macrophage-dependent cytostasis.

PMID- 7636259
TI  - Differential up-regulation of HLA class I molecules on neuronal and glial cell
      lines by virus infection correlates with differential induction of IFN-beta.
AB  - Adult neurons normally lack the expression of MHC class I molecules, which has
      implications on virus clearance from the central nervous system. The author
      previously demonstrated that HLA class I up-regulation in measles virus (MV)
      infected glial cells is primarily mediated by IFN-beta. In contrast, this study
      demonstrates that MV-infection of the neuronal cell lines IMR-32 and CHP-126
      fails to up-regulate HLA class I expression, which was associated with an
      inability of MV to induce IFN-beta in the neuronal cell lines. However, treatment
      with IFN-beta on coculture of the IMR-32 neuronal cell line with MV-infected
      glioma cells resulted in the up-regulation of HLA class I on the former, which
      could be neutralized by anti-IFN-beta Ab. The inability of MV to up-regulate HLA
      class I expression on the neuronal cell line IMR-32 was not virus specific
      because similar findings were observed with mumps virus or stimulation with the
      synthetic dsRNA polyinosinic polycytidylic acid (PIPC). Induction of IFN-beta
      gene expression by virus requires binding of NF-kappa B to the positive
      regulatory domain II element of the IFN-beta promoter. Our studies indicate that
      MV, TNF-alpha, or PIPC induces NF-kappa B (p50 and p65 subunits) binding to
      positive regulatory domain II in the glioma cell line. In contrast, such activity
      was induced by TNF-alpha but not MV or PIPC in the neuronal cell line IMR-32.
      This indicated that HLA class I expression is differentially regulated in glial
      and neuronal cell lines in response to MV, which correlates with differential
      binding of NF-kappa B to the IFN-beta promoter and induction of IFN-beta gene
      expression.

PMID- 7636260
TI  - Divergence in macrophage insulin-like growth factor-I (IGF-I) synthesis induced
      by TNF-alpha and prostaglandin E2.
AB  - Increased synthesis of insulin-like growth factor I (IGF-I), a fibroblast growth
      factor, is induced in murine macrophages by TNF-alpha. TNF-alpha also induces
      macrophages to express cytocidal activity, but only during costimulation with
      IFNs. Since prostaglandin E2 (PGE2) is known to inhibit macrophage cytocidal
      activity, its possible reciprocal enhancement of IGF-I synthesis was examined.
      PGE2 or dibutyryl cyclic AMP (dbcAMP) stimulated the synthesis of IGF-I similarly
      to TNF-alpha in magnitude and time course. TNF-alpha did not increase IGF-I
      synthesis by first inducing PGE2 synthesis, because indomethacin was unable to
      block the effect of TNF-alpha. PGE2 did not stimulate IGF-I synthesis by first
      inducing TNF-alpha production, because 1) anti-TNF-alpha Ab did not block PGE2
      induced IGF-I synthesis, and 2) PGE2 down-regulated TNF-alpha mRNA levels and did
      not affect levels of the cytokine in supernatants. Moreover, the difference in
      the induction of IGF-I was observed at the level of signal transduction, in that
      PGE2 and dbcAMP increased cAMP-dependent protein kinase (PKA) activity, whereas
      TNF-alpha stimulated the mitogen-activated protein (MAP) kinase pathway.
      Divergence between the two pathways was also noted in the regulation of IGF-I at
      the mRNA level, and an additive effect on IGF-I synthesis was observed when cells
      were incubated with the combination of TNF-alpha plus PGE2 or dbcAMP.
      Collectively, these data suggest that TNF-alpha and PGE2 stimulate IGF-I
      synthesis in macrophages by two separate pathways, and that PGE2 acts as a
      positive stimulus for IGF-I synthesis through a cyclic AMP/PKA pathway.

PMID- 7636261
TI  - An essential role of prostaglandin E on mouse mast cell induction.
AB  - We previously established a system for induction of mucosal-type mast cells from
      mouse spleen cells by long term culture without exogenous IL-3. FCS was important
      and was able to be divided into mast cell-inducible and non-mast cell-inducible
      sera. LPS contaminated in FCS was responsible for the mast cell induction.
      However, we unexpectedly found that both supernatants recovered from the cultures
      with mast cell-inducible and non-mast cell-inducible sera contained endogenous IL
      3. Furthermore, addition of rIL-3 to the cultures with non-mast cell-inducible
      sera had no effect or induced only a small number of mast cells. This indicates
      that IL-3 alone is not enough for mast cell induction and that some inflammatory
      factor(s) induced by LPS is also essential. Prostaglandin E1 (PGE1) and PGE2
      induced mast cells in a dose-dependent manner when added into the cultures. The
      activity of LPS for mast cell induction was inhibited by indomethacin. However,
      indomethacin failed to inhibit the mast cell induction by exogenous PGE.
      Exogenous PGE antagonized the indomethacin-induced inhibition of mast cell
      induction by LPS. Cholera toxin and dibutyryl cyclic AMP (cAMP) also induced mast
      cells. The A and B subunits of cholera toxin, PGF2 alpha, PGD2, and dibutyryl
      cGMP failed to induce mast cells. Furthermore, mast cell induction by PGE was
      dose-dependently suppressed by inhibitors for cAMP-dependent A kinase. The above
      results show that for mast cell induction, IL-3 needs the cooperation of PGE or
      other stimulants that can elevate the production of the second messenger cAMP in
      mast cell precursors.

PMID- 7636262
TI  - Cell surface molecules related to factor J in human lymphoid cells and cell
      lines.
AB  - Factor J (FJ) is a cationic glycoprotein that is able to inhibit in vitro both
      the classical and alternative pathways of complement. FJ was purified to
      homogeneity from human urine by sequential chromatographic steps. To examine the
      expression of FJ in human cells we obtained mAbs against urine-purified FJ.
      Preliminary studies by immunocytochemistry revealed that one of the anti-FJ mAbs
      recognized cell surface components of certain cell lines, such as K562 and U937
      cells, so we have focused subsequently on the detection of these homologue
      membrane-bound FJ Ags (FJ-h Ags) in cell lines of lymphoid (Ramos and Jurkat) and
      mieloyd (U937 and K562) origin, as well as in peripheral blood cells. The flow
      cytometry analysis of the examined cell lines revealed partial staining ranging
      from 10% (U937) to 29% (K562) positive cells. Flow cytometry of peripheral blood
      cells showed a positive staining in a small but consistent population of
      lymphocytes (mean = 11%, n = 17) but none at all on monocytes, granulocytes,
      erythrocytes, or platelets. Double Ab immunostaining of lymphocytes showed that
      the FJ-h positive population included mainly B lymphocytes (a mean of 63% CD19+
      were FJ-h positive). When we analyzed peripheral blood lymphocytes from a patient
      with chronic lymphocytic leukemia B (95% CD19+/CD5+), the majority of these (55%)
      bore FJ-h on their surface. Acid strip of these cells did not abrogate the
      surface staining, which supports the finding that the Ag is tightly bound to the
      membrane. Immunoprecipitation from U937 cell lysates showed a single 65 kDa band
      under reducing conditions. FJ-h Ags purified from K562 and U937 cells displayed
      inhibitory activity in the functional EAC14 assay for the classical complement
      pathway, as did urine FJ, and they were recognized immunochemically by five
      different (one polyclonal and four monoclonal) anti-FJ Abs. In conclusion, FJ
      homologues are present in the membranes of several human cell lines that show
      functional and antigenic characteristics similar to soluble urine FJ. They are
      also found in a small subset of peripheral blood lymphocytes, mainly B cells. The
      structural relationship between both soluble urine FJ and these membrane-bound FJ
      h remains to be established.

PMID- 7636263
TI  - The delayed-type hypersensitivity reaction is dependent on IL-8. Inhibition of a
      tuberculin skin reaction by an anti-IL-8 monoclonal antibody.
AB  - Cell-mediated immune reactions are essential to our immune response toward
      foreign organisms such as microorganisms, or in the response toward foreign
      tissue Ags, as seen in the rejection of allogeneic transplanted organs. Similar
      reactions form the basis for the development and the progression of delayed-type
      hypersensitivity (DTH) reactions. We found that the alpha-chemokine IL-8 plays an
      important pathophysiologic role for the development of a DTH reaction because
      infusion of a neutralizing anti-IL-8 mAb (WS-4) was able to suppress the
      development of a tuberculin skin reaction in rabbits, as judged by histologic,
      biochemical, and clinical examinations. Thus, the number of neutrophil
      granulocytes and lymphocytes at the site of tuberculin injection was decreased
      considerably, and the clinical signs of inflammation were suppressed almost
      completely at 24 h after intracutaneous injection of tuberculin, as judged by the
      size of the infiltrates. In contrast, we did not see any effect on the visible
      erythema of the skin. We found that the tissue content of myeloperoxidase (MPO),
      reflecting the number of infiltrating neutrophils, was lowered significantly.
      Furthermore, immunohistochemical analysis confirmed that IL-8 immunoreactivity is
      actually enhanced in the skin of positive tuberculin reactions. The results
      indicate that IL-8 plays an important role for the early accumulation of
      leukocytes in the skin and for the clinical signs of a DTH reaction.

PMID- 7636264
TI  - Chemokine binding and activities mediated by the mouse IL-8 receptor.
AB  - In humans and rabbits two similar IL-8R mediate the chemotaxis and activation of
      neutrophils induced by alpha chemokines. We present data to suggest that there is
      only one such IL-8R gene in mice. We then use mice with a targeted deletion of
      this gene to characterize alpha chemokine ligands that signal via the mouse IL
      8R. These experiments show that mouse macrophage inflammatory protein 2 binds the
      receptor with high affinity (Kd = approximately 1.5 nM) and potently activates
      both an intracellular Ca2+ flux and a chemotactic response, events absent in
      neutrophils from receptor-deleted mice. Mouse KC is approximately 10-fold less
      potent. These results show that macrophage inflammatory protein 2 and KC potently
      activate mouse neutrophils via a unique IL-8R, and these proteins may function as
      the major proinflammatory alpha chemokines in mice.

PMID- 7636265
TI  - Association between Lyn protein tyrosine kinase (p53/56lyn) and the beta subunit
      of the granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors in a
      GM-CSF-dependent human megakaryocytic leukemia cell line (M-07e).
AB  - The role of the lyn product (p53/p56lyn), a membrane-associated protein tyrosine
      kinase in the signaling pathway used by granulocyte macrophage-CSFR (GM-CSFR) was
      investigated by using the GM-CSF-dependent human megakaryoblastic leukemia cell
      line M-07e. M-07e cells express GM-CSFR and are dependent on GM-CSF for survival
      and proliferation in vitro. Treatment with anti-lyn Abs coimmunoprecipitated,
      along with lyn product, the beta subunit of GM-CSFR and a phosphoprotein with a
      molecular mass of 120 kDa (p120) in the lysates of M-07e cells but not in the
      lysates of human monocyte-derived macrophages (HMDM) or human lymphoid leukemia
      cells. That the 120-kDa phosphoprotein coimmunoprecipitated by anti-lyn Abs is
      the beta subunit of GM-CSFR was confirmed in the immunoprecipitates (IP) of M-07e
      cells with the use of an agarose-conjugated anti-p-tyr mAb. The formation of GM
      CSF/GM-CSFR/lyn signaling complexes was verified in an autoradiographic study
      with anti-lyn IP of M-07e cells that had been bound with 125I-labeled recombinant
      human (rh)GM-CSF. The p120 protein (beta subunit) was not detected in the IP of M
      07e cells with anti-fyn or anti-PI3 Abs. A direct association of Lyn kinase with
      the beta subunit of GM-CSFR was illustrated with a reversed approach showing the
      recovery of Lyn protein in anti-beta (CRS1) but not anti-alpha IP of M-07e cells
      that had been starved for a prolonged period. Finally, the interaction of Lyn
      kinase with the GM-CSFR complexes was further corroborated using anti-GM-CSF
      (G133) mAb, which coimmunoprecipitated both the p120 beta subunit and lyn product
      in the lysates of M-07e cells that had been bound with rhGM-CSF before cell
      lysis. Removal of rhGM-CSF from culture medium for 10 to 12 h resulted in a
      marked decrease in lyn-associated kinase activity but not the beta subunit/lyn
      kinase complex formation. Taken together, our results showed that, in M-07e
      cells, Lyn protein tyrosine kinase (p53/p56lyn) is stably associated with a
      constitutively phosphorylated beta subunit of the GM-CSFR in a manner that seems
      to be independent of lyn kinase activity.

PMID- 7636266
TI  - Cross-linking of CD45 enhances activation of the respiratory burst in response to
      specific stimuli in human phagocytes.
AB  - The phosphotyrosine phosphatase CD45 is expressed on the surface of all
      leukocytes and is known to play a critical role in the regulation of both T and B
      cell function. In contrast, relatively little information exists regarding the
      role of CD45 in the phagocyte lineage. We present evidence that CD45 modulates
      activation of the inducible respiratory burst in normal human neutrophils,
      monocytes, and eosinophils, as measured by luminol-enhanced chemiluminescence. In
      neutrophils, the respiratory burst induced by FMLP (1 microM), granulocyte
      macrophage CSF (GM-CSF; 1 microgram/ml), or TNF-alpha (100 U/ml) was enhanced
      synergistically by CD45 cross-linking. This effect was most striking upon
      stimulation with TNF-alpha, in which cross-linking of CD45 resulted in a 30-fold
      increase in chemiluminescence. Chemiluminescence induced by PMA (100 nM),
      opsonized zymosan (1 mg/ml), LPS (1 microgram/ml), IFN-gamma (100 U/ml), or
      granulocyte CSF (1 microgram/ml) was not affected significantly by CD45 cross
      linking. Similar results were obtained by using iodination for measurement of the
      respiratory burst. In monocytes, CD45 cross-linking significantly increased
      chemiluminescence stimulated by FMLP, GM-CSF, TNF-alpha, and LPS, and GM-CSF- and
      TNF-alpha-induced chemiluminescence was enhanced significantly by cross-linking
      of CD45 on eosinophils. Immunoblot analysis demonstrated that both the rate and
      intensity of TNF-alpha-induced tyrosine phosphorylation were increased by CD45
      cross-linking in neutrophils. Major tyrosine-phosphorylated products include
      proteins with approximate molecular masses of 40 kDa, 70 kDa, 78 kDa, and 110
      kDa. These results provide direct evidence that CD45 is capable of regulating the
      inducible respiratory burst in human phagocytes. On the basis of our findings, we
      postulate that CD45 may mediate coupling of specific cell surface receptors to
      downstream tyrosine kinase-dependent signal-transduction pathway(s) in activated
      phagocytes.

PMID- 7636267
TI  - C-reactive protein binds to Fc gamma RI in transfected COS cells.
AB  - C-Reactive protein (CRP) is an acute phase serum protein in man that binds to
      certain bacterial polysaccharides and to components exposed on damaged cells. CRP
      is bound by receptors on phagocytic cells and functions as an opsonin for its
      ligands. Interactions of CRP with a specific CRP receptor (CRP-R) and with the
      high affinity receptor for IgG, Fc gamma RI, on monocytic cells have previously
      been demonstrated. It was not possible to fully characterize CRP binding to Fc
      gamma RI in these studies, since cells and cell lines expressing Fc gamma RI also
      have the CRP-R. In the present study we examined the interaction of CRP with Fc
      gamma RI in COS-7 cells transfected with a cDNA encoding this receptor.
      Expression of Fc gamma RI and specific CRP binding to transfected cells were
      demonstrated by flow cytometry. By two-color analysis, the cell population
      binding CRP was the same as the population that bound the Fc gamma RI-specific
      mAb 10.1 and 32.2 CRP inhibited the binding of radiolabeled IgG1 and IgG4 by up
      to 60%. A CRP molecule that was mutated in the amino acid sequence homologous to
      the IgG sequence proposed to interact with Fc gamma RI failed to bind to
      transfected cells, but retained the ability to bind to the CRP-R on monocytic
      cells. These studies confirm the binding of CRP to Fc gamma RI and identify a
      site on CRP that is essential for this binding.

PMID- 7636268
TI  - Complement membrane attack complex, perforin, and bacterial exotoxins induce in
      K562 cells calcium-dependent cross-protection from lysis.
AB  - The complement membrane attack complex (MAC), the cytolytic granule protein of
      cytotoxic lymphocytes perforin, the streptococcal exotoxin streptolysin O (SLO),
      and the bee venom polypeptide melittin utilize a similar mechanism to incorporate
      into cell membranes, induce a Ca2+ influx and a rise in intracellular Ca2+
      concentration, and produce cell lysis. At sublytic concentrations, these proteins
      trigger several cellular activities, including protein phosphorylation and
      synthesis. We have recently demonstrated that human leukemic cells treated with
      sublytic doses of human complement become more resistant to lytic complement
      doses. The study has now been extended to include three other pore-formers:
      murine perforin, SLO and melittin. As shown here, sublytic MAC induces in the
      K562 human erythroleukemic cells protection from lytic perforin, and vice versa,
      sublytic perforin induces protection from complement. Also, sublytic SLO and
      melittin increase resistance of K562 cells to lytic complement and perforin
      doses. The capacity of Ca2+ ionophores to induce resistance to the lytic proteins
      has been examined. Exposure of K562 cells to sublytic concentrations of ionomycin
      or A23187 for 1 h at 37 degrees C confers on them resistance to complement- and
      perforin-mediated lysis. The protective effects of the ionophores can be
      abrogated by chelation of extracellular Ca2+ and by inhibition of RNA or protein
      synthesis in the cells. These results indicate the following: 1) nucleated cells
      exposed to sublytic complement MAC, perforin, SLO, or melittin may become
      resistant to the four pore-formers. Physiologically, this may be regarded as an
      immunologic tachyphylaxis. 2) Ca2+ influx induced by these pore-formers is an
      essential and sufficient factor to produce this tachyphylaxis.

PMID- 7636269
TI  - Neutralization of IL-10 increases lethality in endotoxemia. Cooperative effects
      of macrophage inflammatory protein-2 and tumor necrosis factor.
AB  - The overzealous production of pro-inflammatory cytokines during endotoxemia can
      result in shock, multiorgan dysfunction, and even death. The extent of tissue
      injury that occurs in endotoxemia is determined not only by the release of pro
      inflammatory cytokines, but also by the expression of endogenous counter
      regulatory cytokines, such as IL-10. In this study, we defined the role of
      endogenously-produced IL-10 in a murine model of endotoxemia. Initial studies
      indicated that LPS administration to mice i.p. induces a significant time
      dependent increase in plasma IL-10. Passive immunization with anti-IL-10 serum
      before LPS administration resulted in substantial increases in endotoxin-induced
      lethality. Furthermore, the inhibition of IL-10 bioactivity in vivo resulted in a
      greater and more sustained increase in plasma TNF and macrophage inflammatory
      protein-2 (MIP-2) levels, as compared with control animals, which was accompanied
      by early increases in lung polymorphonuclear leukocyte influx and lung capillary
      leak. Finally, anti-IL-10-mediated lethality was significantly abrogated by
      concomitant treatment with anti-MIP-2 serum and/or sTNFR:Fc alone or in
      combination. These observations indicate that TNF and MIP-2 are important
      cytokine mediators during endotoxemia, and endogenously produced IL-10 is
      instrumental in down-regulating the overzealous production of both TNF and MIP-2
      that occurs in response to systemic endotoxin exposure.

PMID- 7636271
TI  - Sm and DNA binding by dual reactive B cells requires distinct VH, V kappa, and VH
      CDR3 structures.
AB  - We have previously demonstrated an overlap of the anti-Sm and anti-DNA responses
      in MRL/Mp-lpr/lpr mice. The Ab produced by many anti-Sm hybridomas bind DNA and
      are encoded by Ig V genes used by anti-DNA hybridomas. In addition, some anti-Sm
      Ab that bind DNA have acquired mutations that improve DNA binding, indicating
      that DNA is a selecting Ag in the anti-Sm response. To gain insight into the
      basis for the dual binding ability of these Ab, we coexpressed the H chain from
      the anti-Sm hybridoma 2-12 with nine different L chains. Hybridoma 2-12 binds Sm
      but not DNA, yet expresses the same J558 VH gene as three anti-Sm hybridomas that
      bind ssDNA and at least one anti-DNA hybridoma that does not bind Sm. We found
      that most of the transfectoma Ab bind Sm, but their avidities vary over more than
      3 orders of magnitude. Five of the nine transfectoma Ab bind ssDNA, and none bind
      dsDNA. In general, the ability to bind each Ag follows the binding ability of the
      hybridoma from which the L chain is derived. H Chain swapping experiments
      indicate that the H chain, VH CDR3 in particular, contributes to the binding of
      both Sm and DNA. We conclude that Sm and DNA select for distinct features of VH,
      V kappa, and VH CDR3, suggesting selection by both Ag in the anti-Sm response.

PMID- 7636270
TI  - IL-10 production in cutaneous basal and squamous cell carcinomas. A mechanism for
      evading the local T cell immune response.
AB  - Cytokines play a vital role in the host immune response by regulating the
      development and function of immunocompetent cells. To explore the possibility
      that tumors may alter the host response via release of immunomodulatory
      cytokines, we studied two different skin cancers, basal cell carcinoma (BCC) and
      squamous cell carcinoma (SCC) as models. By RT-PCR, we found that the type 2
      cytokines, IL-4 and IL-10, were strongly expressed in BCC compared with matched
      PBMC. Furthermore, IL-10 was more strongly expressed in SCC compared with benign
      growths. To identify the cell types responsible for production of these
      cytokines, tumor and tumor-infiltrating lymphocyte (TIL) cell lines were derived
      from BCC and SCC biopsy specimens. IL-2 and IFN-gamma mRNAs were expressed in
      TIL, while IL-10 mRNA were strongly expressed in BCC lines. In addition, IL-10
      was detected in culture supernatants from BCC and SCC cell lines by ELISA and in
      tissue sections by immunohistology. TIL lines derived from these tumors
      demonstrated proliferative activity to autologous tumor cells in the presence of
      APCs, dependent on the addition of low concentrations of rIL-2 or neutralizing
      anti-IL-10 mAb in the culture medium. Furthermore, treatment of BCC with
      intralesional IFN-alpha induced tumor regression with concomitant up-regulation
      of IL-2 and down-regulation of IL-10 mRNA expression in lesions. These data
      suggest that tumor production of the cytokine, IL-10, may provide a mechanism for
      evading the local T cell-mediated immune response.

PMID- 7636272
TI  - Murine lupus glomerulotropic monoclonal antibodies exhibit differing
      specificities but bind via a common mechanism.
AB  - We recently identified that the glomerular binding activity in MRL/lpr serum
      consists of Abs reactive with DNA/histone adherent to glomerular basement
      membrane (GBM) via type IV collagen. These studies suggest the presence of
      multiple nephritogenic autoantibodies that bind to glomeruli via a common
      mechanism, an hypothesis we tested by producing glomerular binding mAbs from a
      nephritic MRL/lpr mouse. All 7 mAbs produced bound to glomeruli/GBM in a DNase
      inhibitable fashion. The 4 mAbs that bound most avidly to glomeruli/GBM (group I)
      did not bind to DNA per se, and GBM binding after DNase treatment was
      reconstituted by histones or histone/DNA co-addition. The remaining 3 mAbs (group
      II) bound well to DNA, and GBM binding after DNase treatment was reconstituted by
      DNA but not histones. Collagenase (but not heparitinase) inhibited GBM binding of
      all mAbs and impaired the ability of nuclear Ags to reconstitute binding. None of
      the mAbs bound to type IV collagen per se. Using defined nuclear Ags, two group I
      mAbs bound specifically to histone H2A-H2B-DNA complexes, one bound specifically
      to intact chromatin, and one was polyreactive to histones. Group II mAbs bound to
      any nuclear Ag-containing DNA. Binding to nuclear Ags by all mAbs was altered if
      type IV collagen was used as the assay substrate, and in this context the common
      Ag for all mAbs was intact chromatin. In sum, glomerular binding mAbs exhibit
      differing antigenic specificities, but can be identified as either predominantly
      anti-histone/nucleosome (group I) or anti-DNA (group II). Regardless, binding to
      chromatin adherent to type IV collagen is a common property of all such mAbs.

PMID- 7636273
TI  - TCR/CD3 complex-mediated signal transduction pathway in T cells and T cell lines
      from patients with systemic lupus erythematosus.
AB  - We studied the TCR/CD3 complex-mediated signal transduction pathway in freshly
      isolated T cells and T cell lines from patients with systemic lupus erythematosus
      (SLE). The peak and 5-min anti-CD3 mAb-mediated free intracytoplasmic Ca2+
      concentration ([Ca2+]i) increase was statistically significant higher in fresh T
      cells from SLE patients than in control T cells. Increased CD3-mediated [Ca2+]i
      responses were observed in T cells from patients with SLE but not in T cells from
      other rheumatic diseases. Furthermore, significantly increased CD3-mediated
      [Ca2+]i responses were observed in T cell lines from SLE patients but not from
      controls. Although the [Ca2+]i response did not correlate with the global SLE
      disease activity or individual clinical manifestations, it was significantly
      higher in the group of patients who were not on treatment. Both CD4+ and CD8+ T
      cell subsets from peripheral blood cells and T cell lines displayed higher CD3
      mediated [Ca2+]i responses than their normal counterparts. The peak of the
      response occurred earlier in the patient than in the normal group. The amount of
      Ca2+ that was released from the intracellular stores was higher in lupus than
      control T cells. The TCR/CD3-induced production of inositol phosphate metabolites
      in SLE cells was comparable with controls. The sarcoplasmic and endoplasmic
      reticulum Ca(2+)-ATPase inhibitor thapsigargin-induced [Ca2+]i response was
      similar in both SLE and normal T cells. Our experiments demonstrate for the first
      time a definite abnormality in the early steps of the TCR/CD3-mediated signal
      transduction pathway in T cells from SLE patients that involves increased release
      of Ca2+ from intracellular stores.

PMID- 7636274
TI  - T cell receptor V beta complementarity-determining region 1 peptide
      administration moderates immune dysfunction and cytokine dysregulation induced by
      murine retrovirus infection.
AB  - Murine AIDS, induced by LP-BM5 murine leukemia retrovirus infection, causes a
      progressive and profound immunodeficiency in female C57B1/6 mice. Previously, we
      reported that autoantibodies were elevated during the initiation phases of this
      murine retrovirus infection and bound peptide determinants corresponding to CDR1
      of several TCR V beta-chains. Therefore, we designed studies to determine whether
      administration of a major autoimmunogenic TCR V beta CDR1 peptide before or after
      infection with LP-BM5 retrovirus would modulate retrovirus-induced dysregulation
      of T cell function. Administration of the TCR V beta CDR1 peptide before murine
      retrovirus infection significantly prevented its suppression of splenic NK cell
      activity, T and B cell proliferation, and monokine (IL-6 and TNF-alpha) and Th1
      cytokine (IL-2 and IFN-gamma) release by splenocytes, and inhibited retrovirus
      induced elevation of Th2 cytokine (IL-5 and IL-10). Similar data were obtained
      with peptide immunization 2 wk after murine retrovirus infection at 6 and 16 wk
      postinfection. However, delaying peptide immunization until severe suppression of
      T and B cell mitogenesis had occurred did not restore their functions.
      Immunization with TCR V beta peptide prevents development of retrovirus-induced
      immune dysfunction, which suggests a possible pathogenic role of autoreactive T
      cells as regulatory elements.

PMID- 7636275
TI  - Hepatitis C: clinical aspects.

PMID- 7636276
TI  - The potential reduction of microbial contamination of central venous catheters.
AB  - The microbial contamination of stopcock entry ports attached to central venous
      catheters (CVC) was determined using a specially designed swab. The swab was made
      of a highly porous material, Porex, and was designed to fit exactly into the
      entry port of stopcocks. The swab was used to determine the frequency of
      microbial contamination of entry ports attached to CVC in patients located on an
      Intensive Care Unit. Of the 200 swabs obtained 44 (22%) contained microorganisms.
      Coagulase-negative staphylococci were recovered from 43 of the swabs and
      diphtheroid bacilli from 1 swab. In vitro studies were carried out to investigate
      the efficiency of the swab in removing excess residual fluid and organisms from
      entry ports. The swab absorbed relatively large numbers of bacteria within
      seconds. When entry ports were inoculated with between 10(3) and 10(5) cfu of
      either Staphylococcus epidermidis or Klebsiella pneumoniae greater than 99% of
      the organisms were absorbed by the swab (P < 0.01). The absorbent swab was more
      efficient at removing S. epidermidis from the entry port when compared to a
      standard cotton swab (P < 0.01). In vitro this absorbent swab reduced the
      potential for catheter contamination resulting from migration of organisms from
      the entry port via the intraluminal route. The use of the swab in the clinical
      situation may reduce the incidence of CVC-related infections.

PMID- 7636278
TI  - Salmonellosis and mycotic aneurysm of the aorta. A report of 10 cases.
AB  - We report a 5 year experience of 10 cases of mycotic aneurysms of the aorta
      caused by salmonella infection. Of the 10 patients, nine were males and one was
      female in an age range from 60 to 80 years with a mean of 71 years. The major
      clinical manifestations were fever, abdominal or back pain, pulsatile abdominal
      mass and leucocytosis. The diagnosis was based on clinical symptoms and signs and
      positive blood or tissue cultures. The main confirmatory procedure was computed
      tomography (CT). Two year survival rate was 20%. Five patients died during
      hospitalisation, without surgery. Three patients died within 2 months of surgery.
      The other two patients, treated surgically and by intensive antibiotic therapy,
      survived. Death resulted usually from recurrent infection and graft leakage.
      Contrary to previous reports, salmonella mycotic aneurysm is still common in this
      geographical area and the prognosis is poor.

PMID- 7636277
TI  - Chlamydia pneumoniae: risk factors for seropositivity and association with
      coronary heart disease.
AB  - BACKGROUND: Two studies have suggested that seropositivity for Chlamydia
      pneumoniae (C. pneumoniae) is a risk factor for coronary heart disease (CHD) but
      the association remains tenuous. Further data is required in other populations to
      consolidate this observation. AIMS: Initially to determine descriptive risk
      factors for C. pneumoniae seropositivity in a general population sample and
      subsequently to examine the relation of seropositivity for this organism to CHD
      for the first time in a British population. SETTING: A single general practice
      health screening clinic and a cardiology clinic involving patients predominantly
      residing in south London and Surrey. SUBJECTS: 210 consecutive caucasian men
      (62%) and women (38%) aged 18-79 including 67 men aged 45-65. This latter group
      acting as controls were then also compared with 103 consecutive males aged 45-65
      with angiographically confirmed coronary heart disease. METHODS: A questionnaire
      was administered by a research nurse and serum was analysed for IgG and IgA
      against C. pneumoniae and other Chlamydiae by a microimmunofluorescence test.
      Serum was said to be low positive at a specific IgG antibody titre of 16-32, and
      high positive if 64 or greater. RESULTS: Amongst the general practice health
      screening clinic population 14 subjects (7%) were excluded due to possible cross
      reactivity with other Chlamydia species (predominantly C. trachomatis). Of the
      remaining 196 subjects, 13 (6%) had high positive C. pneumoniae IgG titres, 68
      (35%) had low titres and 125 had no detectable antibody. After adjustment for
      sex, age, smoking history, social class and family size only one risk factor for
      high positive titres in this group was identified, which was the number of
      children currently living in the home (OR 2.29 (1.09-4.80), P = 0.03). No factors
      were significantly related to low titres. 22/100 (22%) cases with coronary heart
      disease and 3/64 (4.7%) of controls had high positive IgG titres for C.
      pneumoniae. Similarly 21% of cases and 9.4% of controls had positive C.
      pneumoniae specific IgA serology. 45% of cases and 44% of controls had low C.
      pneumoniae IgG titres. The association of CHD with a C. pneumoniae IgG titre of
      64 or above was independent of all risk factors (OR 7.4 (1.7-33.1), P < 0.01).
      CONCLUSION: Serological evidence of C. pneumoniae infection is common amongst
      healthy British subjects. Smoking and social class are not important confounding
      variables in this study. Reinfection from contact with infected children in the
      home may be important in inducing higher titres in some subjects. These higher
      titres are more prevalent in subjects with coronary heart disease in the U.K. as
      reported in Finland and the U.S.A., and provide further evidence that C.
      pneumoniae may be important in the pathogenesis of this condition in these
      populations.

PMID- 7636279
TI  - Q-fever pneumonia in the Negev region of Israel: a review of 20 patients
      hospitalised over a period of one year.
AB  - BACKGROUND: Three-hundred and forty-six patients with community acquired
      pneumonia were included in a prospective study of patients hospitalised over a 12
      month period in the Soroka Medical Center in Beer-Sheva, Israel. Q-fever
      pneumonia (QFP) was diagnosed in 20 patients (5.8%). A detailed epidemiological
      and clinical description of this disease, is presented. METHODS: QFP was
      diagnosed by conventional criteria using a commercial immunofluorescent assay.
      RESULTS: The age of patients was 41 +/- 14 years (mean +/- S.D., range 20-69).
      Twelve of the patients were males. No concomitant or chronic disease was present
      in 16 patients. Chest radiograms revealed alveolar or air space pneumonia in 10
      patients, bronchopneumonia in nine and interstitial pneumonia in one patient. The
      mean febrile period was 10.5 +/- 5.3 days. There was serological evidence of co
      infection with Mycoplasma pneumonia in six patients, and with Legionella
      pneumophila in one patient. Patients treated with beta-lactam antibiotics
      recovered as quickly as those treated with tetracyclines or erythromycin.
      CONCLUSIONS: The Negev region of Israel is an endemic area for Q-fever. The
      diagnosis of QFP can be made only on the basis of a specific serological test.
      Clinical, radiologic or laboratory findings are not diagnostically definitive.
      The importance of specific therapy is unclear.

PMID- 7636280
TI  - Systemic amphotericin B versus fluconazole in the management of antibiotic
      resistant neutropenic fever--preliminary observations from a pilot, exploratory
      study.
AB  - A pilot exploratory study was undertaken to collect preliminary information
      relating to safety and overall outcome in using intravenous fluconazole (FLUC)
      for managing antibiotic resistant neutropenic fever (ARNF), with the objective of
      assessing feasibility of performing a larger prospective controlled study.
      Patients who were neutropenic from treatment for leukaemia or bone marrow
      transplantation, received either fluconazole (FLUC) or amphotericin B (AB). Eight
      of 16 patients (50%) on FLUC and 21 of 25 patients (84%) on AB defervesced; the
      mean time to defervescence was 11.0 +/- 10.0 days for FLUC compared to 7.7 +/-
      6.3 days for AB, and a similar proportion in each treatment group defervesced
      within 5 days (50% vs. 52%), respectively. Six of 16 patients (37.5%) on FLUC and
      three of 25 patients (12%) on AB developed overt invasive fungal disease,
      including pulmonary aspergillosis (FLUC 4 cases, AB 2 cases) and invasive
      candidiasis (FLUC 2 cases, AB 0 cases). The mean time to these events was 19.5 +/
      13.4 (FLUC) and 9.0 +/- 3.6 (AB) days. The fungal related mortality rates were
      higher in the FLUC group: five of 16 patients (31%) vs. two of 25 patients (18%)
      died respectively; the time to fungal death was 43.2 +/- 18.2 (FLUC) and 25.0 +/-
      18.4 (AB) days. This tendency towards a more favourable outcome in patients on AB
      may have been due to absence of prior fluconazole prophylaxis in patients
      subsequently receiving IV FLUC. Analysis of a small subgroup of patients who had
      all received prior prophylaxis with clotrimazole only, indicated that a greater
      number of patients subsequently receiving IV FLUC died from fungal disease (5/16
      vs.0/6, P = 0.09).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7636281
TI  - Cerebral mass lesions due to cytomegalovirus in patients with AIDS: report of two
      cases.
AB  - Cytomegalovirus (CMV) is an increasingly important opportunistic pathogen in
      patients with HIV infection and advanced immune deficiency. Neurological
      complications due to CMV cause significant morbidity but may be treatable with
      specific anti-viral therapy: cerebral mass lesions are not a generally recognised
      manifestation. We report two patients with CMV encephalitis presenting as a
      cerebral mass lesion, with simultaneous occurrence of a pleuro-pulmonary mass
      also caused by CMV in one case, and with concurrent polyradiculomyelopathy in the
      other. The spectrum of previously reported clinical and radiological features of
      CNS involvement in AIDS is discussed. CMV should be considered in the
      differential diagnosis of cerebral mass lesions in patients with HIV infection
      and severe immune deficiency so that anti-viral therapy can be rapidly deployed.

PMID- 7636282
TI  - Scedosporium prolificans, a multi-resistant fungus, from a U.K. AIDS patient.
AB  - We report the first isolation of Scedosporium prolificans (inflatum) in the U.K.
      The patient, with advanced AIDS and neutropenia, had respiratory tract
      colonisation over many months without invasive disease despite neutropenia, while
      on itraconazole therapy. The organism was resistant in vitro to all licensed
      systemic antifungal agents tested.

PMID- 7636283
TI  - Asymptomatic visceral leishmaniasis in a child with acute lymphoblastic
      leukaemia.
AB  - Visceral leishmaniasis was detected incidentally in a patient with acute
      lymphoblastic leukaemia in remission, during maintenance therapy. Absence of
      fever, a normal haemogram, normal serum globulins, a negative serology and
      testicular involvement were the hallmarks of the case. Treatment with sodium
      stibogluconate (20 mg/kg for 55 days) failed. Subsequent therapy with pentamidine
      resulted in complete parasite clearance. Prolonged therapy with pentavalent
      antimony compounds or a higher dose of second line drugs such as pentamidine are
      recommended for complete clearance.

PMID- 7636284
TI  - Erysipeloid infection in a sheep farmer with coexisting orf.
AB  - Erysipeloid is a rarely reported zoonotic infection caused by Erysipelothrix
      rhusiopathiae. We report a case of coexisting erysipeloid and orf infections in a
      sheep farmer, an association not previously recorded to our knowledge.

PMID- 7636285
TI  - Kawasaki-like syndrome in an HIV positive adult.

PMID- 7636286
TI  - Influenza surveillance in N. Greece during 1983-1993.
AB  - Following the WHO programme to monitor influenza, the National Influenza Centre
      for N. Greece presents the results of a laboratory surveillance during 1983-93.
      Influenza viruses were isolated every year except for 1986-87 and 1987-88
      seasons. Type A viruses predominated in 1983-84, 1985-86, 1988-89 and 1989-90.
      Type B viruses were prevalent in 1990-91 and 1992-93. Both types of A and B
      viruses circulated concurrently in the community during the winters of 1984-85
      and 1991-92. Seroconversions (CF tests) occurred each year against A, B or both
      types of influenza viruses. In 1986-87 and 1987-88 when no viruses were
      recovered, there were seroconversions to B viruses, suggesting influenza B
      activity in the area. Serological surveys by haemagglutination inhibition (HI)
      tests were also conducted in 1986-87 and 1988-89. The patterns of the isolated
      strains were similar to those recorded worldwide at the same time. There have
      been however differences in the virulence of the viruses and the duration of
      influenza seasons in this part of the world during 1983-93.

PMID- 7636287
TI  - Community-acquired infections among children in an urban environment: a 2-year
      prospective study in Liverpool, U.K.
AB  - Community-acquired infections are an important cause of admission of children to
      hospital. We have made a 2-year prospective study of 1,599 children admitted with
      infection to the Royal Liverpool Children's Hospital in order to determine the
      pattern of infections, their seasonal distribution and the role of the laboratory
      in isolating causative agents. Respiratory infections (32% cases) and
      gastroenteritis (28% cases) were the principal causes of admission. Of all
      admissions, 64% were children aged less than 1 year. Appropriate specimens were
      obtained and/or investigations made of 48% cases. Overall, a causative agent was
      determined in 21% cases. Individual pathogens showed marked seasonality.
      Respiratory syncytial virus, rotavirus and Shigella species were found more often
      in the winter months, while Salmonella species and adenovirus infections were
      most common in the summer. The results provide local data that is relevant to
      both public health and hospital planning. They also emphasise the need for
      continuing surveillance of community-acquired infections.

PMID- 7636288
TI  - Necrotising fasciitis and 'flesh eating virus' syndrome.

PMID- 7636289
TI  - Erysipelothrix rhusiopathiae bacteraemia in a patient without endocarditis.

PMID- 7636291
TI  - Hearing loss following measles vaccination.

PMID- 7636290
TI  - Simultaneous infection by a sensitive and a multiresistant strain of Salmonella
      paratyphi A.

PMID- 7636292
TI  - Listerial brain abscess in an immunocompetent adult with a predisposing
      intestinal condition.

PMID- 7636293
TI  - Neurosyphilis as a cause of dementia. Does it still exist?

PMID- 7636294
TI  - Bacterial meningitis: causes for concern. The Research Committee of the BSSI.
AB  - The case notes of 305 patients admitted to hospitals in the U.K. with a diagnosis
      of bacterial meningitis were studied retrospectively and several items of concern
      emerged. These included: no antibiotics given to patients (82.6%) pre-admission
      and blood cultures and throat swabs were not obtained routinely. From the figures
      presented lumbar puncture appeared to be justified in patients without
      contraindications. About half the patients with a rash would have remained
      undiagnosed without a lumbar puncture even if allowance was made for those who
      did not have a blood culture.

PMID- 7636295
TI  - Hepatitis C: the structure and biology of the virus and diagnostic tests.

PMID- 7636296
TI  - Pemphigus vulgaris and pemphigus foliaceus sera show an inversely graded binding
      pattern to extracellular regions of desmosomes in different layers of human
      epidermis.
AB  - We analyzed the location of binding sites for pemphigus vulgaris (PV) antigen and
      pemphigus foliaceus (PF) antigen in the human epidermis using serum samples
      obtained from three patients with PV and three patients with PF. Confocal laser
      scanning microscopy, immunofluorescent examination of ultrathin cryosections, and
      immunoperoxidase electron microscopy demonstrated discontinuous dots along the
      epidermal cell surfaces. Immunogold electron microscopy of ultrathin cryosections
      showed specific binding of PV and PF autoantibodies only to desmosomes. Post
      embedding immunogold electron microscopy using cryofixation and cryosubstitution
      enabled the whole depth of the epidermis to be examined and the binding of PV and
      PF autoantibodies to be quantitated by counting gold particles. Both PV and PF
      autoantibodies bound to all desmosomes in the epidermis, but not to the surface
      of the non-desmosomal keratinocytes. The majority of auto-antibody binding
      occurred in the extracellular domain (PV, 62%; PF, 69%). The statistical analysis
      of two-way analysis of variance regarding the number of gold particles labeling a
      single desmosome confirmed a significant interaction between subtypes of
      pemphigus (PV and PF) and the different epidermal cell layers (p < 0.044). The
      results indicate that the number of gold particles bound to individual desmosomes
      with PV sera was significantly higher in the lower epidermis than in the upper
      epidermis, and that of PF sera showed reciprocal pattern. This inversely graded
      binding pattern suggests heterogeneity of the composition of the desmosomes,
      which may explain the differences in level of acantholysis between PV and PF.

PMID- 7636297
TI  - 72-kD heat shock protein is a mediator of resistance to ultraviolet B light.
AB  - We have shown previously that human epidermal keratinocytes in situ and in vitro
      constitutively express high levels of the 72-kD heat shock protein (hsp72) and
      that hsp72 expression in these cells can be further induced with heat treatment.
      In the present study, we continue our investigation of the ultraviolet (UV) B
      protective effect of hyperthermic treatment and ask whether hsp72 is a mediator
      of heat-shock-induced UVB resistance. The results of our experiments demonstrate
      that heat treatment (42 degrees C for 4 h) before UVB exposure is able to
      increase significantly the UVB resistance of the epidermal carcinoma cell line
      A431. Heat-induced UVB resistance was most pronounced if the cells were exposed
      to UVB immediately after heat treatment. The protective effect was not detectable
      beyond a recovery period of 12 h. To investigate the role of hsp72 in
      hyperthermia-induced UVB resistance, we inhibited the expression of this protein
      using either a specific antisense oligodeoxynucleotide or quercetin, a flavonoid
      that has been shown to down-regulate hsp expression. Treatment with the oligomer
      as well as with quercetin significantly increased the susceptibility of A431 to
      UVB-induced damage and nullified the protective effect of heat preconditioning. A
      noncomplementary control oligodeoxynucleotide had no significant effect. These
      results indicate that heat treatment is able to induce a state of increased
      resistance to the deleterious effects of UVB in human keratinocytes in vitro.
      hsp72 is a molecular mediator of this protective effect, and its constitutive
      expression in human epidermal keratinocytes may be an important mechanism for the
      protection of human epidermis from UVB-induced damage.

PMID- 7636298
TI  - Immortalized rat whisker dermal papilla cells cooperate with mouse immature hair
      follicle buds to activate type IV procollagenases in collagen matrix coculture:
      correlation with ability to promote hair follicle development in nude mouse
      grafts.
AB  - An in vivo nude mouse graft model and an in vitro collagen matrix culture system
      were used to study interactions of immature hair follicle buds from newborn mice
      with clonally derived AdE1A-12S-immortalized rat whisker dermal papilla cell
      lines. Of the 19 available dermal papilla cell lines, four consistently supported
      good hair follicle development and hair growth in grafts. Seven cell lines were
      clearly negative in this assay, and the remaining eight cell lines yielded poor
      to moderate hair growth. As a correlate to in vivo extracellular matrix
      remodeling accompanying hair follicle development, type IV collagenase activity
      in the medium from cocultures of dermal papilla cells and hair follicle buds was
      analyzed by gelatin zymography. Hair follicle buds cultured alone secrete
      primarily the 92-kDa type IV procollagenase. Cocultivation of hair follicle buds
      with eight of the dermal papilla cell lines resulted in activation of this
      proenzyme and activation of the 72-kDa and 92-kDa type IV procollagenases
      produced by the dermal papilla cells. Seven of these eight dermal papilla cell
      lines support hair growth in the graft system. In the absence of dermal papilla
      cells, several growth factors induced activation of the 92-kDa procollagenase
      secreted by hair follicle buds cultured in serum-free medium: epidermal growth
      factor, transforming growth factor alpha, acidic fibroblast growth factor, and
      keratinocyte growth factor. The current working hypothesis is that a) hair
      follicle epithelial cells interact with dermal papilla cells in coculture by
      mutual induction of growth factors and cytokines that stimulate the release and
      activation of matrix remodeling proteases; and b) the ability of dermal papilla
      cells to interact with hair follicle epithelial cells in this way may be crucial
      for controlled dermal matrix remodelling during HF development.

PMID- 7636299
TI  - Enhanced expression of interstitial collagenase, stromelysin-1, and urokinase
      plasminogen activator in lesions of dermatitis herpetiformis.
AB  - Because dermatitis herpetiformis is characterized by neutrophilic inflammation
      and destructive changes in the basement membrane zone, we studied the in situ
      expression of interstitial collagenase and stromelysin-1 in 11 lesions. A
      prominent signal for collagenase mRNA was consistently detected in the basal
      keratinocytes of rete ridges surrounding the neutrophilic abscesses in 10 of 11
      lesions, and the expression was independent of the age of the lesion and the
      migratory state of the basal keratinocytes. Expression of stromelysin-1 was
      detected in seven of 11 lesions and co-localized with collagenase. No expression
      of the 92-kDa gelatinase mRNA or matrilysin protein was found in the vicinity of
      neutrophilic accumulations or the damaged basement membrane. Urokinase-type
      plasminogen activator mRNA was found in basal keratinocytes in seven of nine
      samples. Collagenase, stromelysin-1, and urokinase-type plasminogen activator
      were not expressed in normal-appearing skin of patients with dermatitis
      herpetiformis. Our results suggest that in lesions of dermatitis herpetiformis,
      collagenase and stromelysin-1 may be induced in basal keratinocytes by neutrophil
      cytokines or by altered cell-matrix interactions through contact of keratinocytes
      with the matrix due to damaged basement membrane. Stromelysin-1, in particular,
      may contribute to formation of blisters by degrading basement membrane
      components.

PMID- 7636300
TI  - Matrix metalloproteinase matrilysin is constitutively expressed in adult human
      exocrine epithelium.
AB  - The proteolytic activity of matrix metalloproteinases is involved in normal and
      disease-related remodeling processes. One member of this family, matrilysin, can
      degrade a wide spectrum of connective tissue proteins, suggesting that this
      enzyme is involved in numerous and diverse biologic processes. In fact, recent
      studies have shown that matrilysin is expressed in developing hair follicles and
      glands. Using in situ hybridization and immunohistochemistry, we examined the
      sites of matrilysin expression in normal and diseased adult skin. In normal
      mature skin, matrilysin mRNA and protein was strongly and consistently expressed
      in ductal cells and in some secretory cells of all eccrine and apocrine glands
      and was not found in any other cell type. A similar tissue distribution was also
      found in numerous benign inflammatory skin lesions, and prominent expression of
      matrilysin mRNA and protein was also found in glandular disorders such as
      axillary hidradenitis and sweat gland tumors. These findings indicate that
      matrilysin is a constitutive product of the epithelium of dermal glands and that
      its expression may not be related to a disease-specific or remodeling process.
      Because of its extensive expression in dermal glands, we assessed whether
      matrilysin might be produced by all exocrine glands. Indeed, we detected
      matrilysin mRNA and immunoreactive protein in the ductal and glandular epithelium
      of mammary and parotid glands, pancreas, liver, prostate, and the serous acini of
      peribronchial glands of the lung. Thus, our findings indicate that matrilysin is
      constitutively produced by exocrine epithelial cells throughout the body. Because
      of its broad catalytic activity, we speculate matrilysin may participate in the
      normal function of exocrine glands by preventing glandular obstruction.

PMID- 7636301
TI  - TNF-R55-specific form of human tumor necrosis factor-alpha induces collagenase
      gene expression by human skin fibroblasts.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a potent inhibitor of connective
      tissue formation. The cellular effects of TNF-alpha are mediated by two distinct
      cell-surface receptors, TNF-R55 and TNF-R75, both present on various types of
      cells, including fibroblasts. In this study we wanted to elucidate the role of
      TNF-R55 as a mediator of the connective tissue effects of TNF-alpha by using a
      mutant, TNF-R55-specific form of human TNF-alpha. This mutant TNF-alpha markedly
      induced collagenase and stromelysin-1 gene expression in dermal fibroblasts, the
      maximal activation (up to 42-fold) being 65%-89% of that noted with wild-type
      human TNF-alpha. In addition, TNF-R55-specific TNF-alpha suppressed type I
      collagen mRNA levels as potently as wild-type TNF-alpha (by 60%). The enhancement
      of collagenase gene expression by TNF-R55-specific TNF-alpha was augmented by
      simultaneous treatment of normal and scleroderma skin fibroblasts with interferon
      gamma, indicating specific enhancement of TNF-R55 signaling pathway by interferon
      gamma. These results show that stimulation of the TNF-R55 signaling pathway is
      sufficient for the inhibitory effects of TNF-alpha on extracellular matrix
      formation by dermal fibroblasts. It is conceivable that due to reduced systemic
      toxicity, TNF-R55-specific forms of human TNF-alpha may prove to be feasible in
      the therapy of fibrotic disorders.

PMID- 7636303
TI  - Functional intercellular adhesion molecule-3 is expressed by freshly isolated
      epidermal Langerhans cells and is not regulated during culture.
AB  - Activation of T lymphocytes by antigen-presenting cells requires the interaction
      of major histocompatibility complex/antigen complexes with the T-cell receptor as
      well as the binding of co-stimulatory molecules to receptors on T cells. Freshly
      isolated epidermal Langerhans cells (LC) do not display a significant number of
      co-stimulatory molecules. After short-term culture, LC express and then
      upregulate intercellular adhesion molecule-1 (ICAM-1) (CD54), leukocyte function
      associated antigen (LFA)-3 (CD58), and B7-1 (CD80) accessory molecules and
      exhibit an enhanced antigen-presenting function. The present study examined the
      presence on human LC of the LFA-1 ligands ICAM-2 (CD102) and ICAM-3 (CD50) and
      their functional role in the activation of allogeneic T cells.
      Immunohistochemistry of skin sections and flow-cytometry analysis of freshly
      procured epidermal cell suspensions showed that LC (CD1a+ or HLA-DR+) expressed
      ICAM-3 but not ICAM-2. After 48-72-h culture in the presence of
      granulocyte/macrophage colony-stimulating factor, LC did not stain for ICAM-2 but
      expressed ICAM-3 at the same level as fresh cells. Incubation of both freshly
      isolated and cultured LC with monoclonal antibodies directed against ICAM-3
      reduced T-cell proliferation (25-75% inhibition) in the primary allogeneic mixed
      leukocyte reaction assay; incubation of cultured LC with anti-ICAM-1 and anti
      ICAM-3 synergistically reduced T-cell response. The results indicate that ICAM-3
      is constitutively expressed and represents an important costimulatory molecule on
      freshly isolated LC but, in contrast to other accessory molecules, is not
      subjected to regulation during LC culture.

PMID- 7636302
TI  - Activity of the type 1 5 alpha-reductase exhibits regional differences in
      isolated sebaceous glands and whole skin.
AB  - The presence of 5 alpha-reductase (5 alpha-R) in skin may indicate that the
      androgen regulation of sebaceous glands and sebum production requires the local
      conversion of testosterone to dihydrotestosterone. The goals of this study were
      to identify which isozyme of 5 alpha-R (type 1 or type 2) is expressed in
      sebaceous glands from facial areas, scalp, and non-acne-prone areas; to determine
      if 5 alpha-R activity is concentrated in sebaceous glands; to assess whether
      there are regional differences in this enzyme's activity; and to test the effects
      of azasteroid inhibitors and 13-cis retinoic acid on 5 alpha-R in these tissues.
      Sebaceous glands were microdissected from facial skin, scalp, and non-acne-prone
      skin (arm, breast, abdomen, leg), and the activity of 5 alpha-R was determined. A
      total of 49 samples from 23 male and 21 female subjects without acne (age range,
      16 to 81 years, 56 +/- 20 years [mean +/- SD]) was analyzed. The biochemical
      properties of the enzyme in each of the samples tested are consistent with those
      of the type 1 5 alpha-R. Minimal to no type 2 5 alpha-R was detected. The level
      of 5 alpha-R activity was significantly higher in the sebaceous glands compared
      to whole skin in facial skin (p = 0.047), scalp (p = 0.039), and non-acne-prone
      skin (p = 0.04). Enzyme activity in sebaceous glands from facial skin and scalp
      was significantly higher than in a comparable amount of sebaceous gland material
      obtained from non-acne-prone areas (32 +/- 6 [mean +/- SEM]), 35 +/- 7 (mean +/-
      SEM) versus 6.0 +/- 3.0 (mean +/- SEM) pmol/min/mg protein, p = 0.014 and 0.007,
      respectively). Finasteride and 13-cis retinoic acid were poor inhibitors of the
      enzyme with 50% inhibitory concentration values greater than 500 nM. These data
      demonstrate that in the skin from older patients without acne the type 1 isozyme
      of 5 alpha-R predominates, its activity is concentrated in sebaceous glands and
      is significantly higher in sebaceous glands from the face and scalp compared to
      non-acne-prone areas, and the action of 13-cis retinoic acid in the control of
      acne is not at the level of 5 alpha-R. Furthermore, we suggest that specific
      inhibition of the type 1 5 alpha-R may offer a viable approach to the management
      of sebum production and, hence, acne.

PMID- 7636304
TI  - Modulation of contact sensitivity responses by bacterial superantigen.
AB  - Superantigens are potent modulators of the immune system, especially T cells.
      Therefore, we determined the influence of superantigens on the T-cell-mediated
      immune response, contact sensitivity. We chose the combination of staphylococcal
      enterotoxin B (SEB) as superantigen and 2,4-dinitrofluorbenzene (DNFB) as the
      contact sensitizer, because in BALB/c mice SEB reacts almost exclusively with V
      beta 8+ T cells, and these cells are capable of transferring contact sensitivity
      to DNFB from sensitized donors to naive syngeneic recipients. Pretreatment with a
      single intradermal injection of 50 ng SEB 24 h before DNFB exposure at the same
      site on the lower abdomen enhanced the induction of contact sensitivity: its
      intradermal injection permitted sensitization with non-sensitizing concentrations
      of DNFB as assessed by ear swelling responses after challenge with DNFB. In
      contrast, pretreatment with repeated intradermal injections of 50 ng SEB every
      other day over at least 1 week inhibited the induction of contact sensitivity
      following sensitization. The enhancing effect of SEB may be explained by the
      creation of a proinflammatory milieu in the skin after a single intradermal
      injection of the bacterial toxin, whereas the inhibitory effect may be due to
      tolerization of V beta 8+ T cells. The data indicate that products of skin
      colonizing bacteria that can serve as superantigens are able to augment or
      inhibit the development of contact sensitivity.

PMID- 7636305
TI  - Identity and functional properties of novel skin-derived fibroblast lines (NS
      series) that support the growth of epidermal-derived dendritic cell lines.
AB  - We have established recently a series of unique cell lines (NS series) from
      dispase-separated mouse epidermis that promote the growth of epidermal-derived
      antigen-presenting cell lines (XS series). The purposes of this study were to
      determine the identity of NS cells and to characterize their functional
      properties. NS cells were distinguishable from leukocytes by the lack of typical
      surface markers and by the failure to respond to leukocyte growth factors.
      Despite their epidermal derivation, NS cells were distinct from keratinocytes by
      the absence of cytokeratins. On the other hand, NS cells were indistinguishable
      from lines of dermal fibroblasts by their a) morphology, b) surface phenotype,
      and c) intracellular deposits of type I collagen. Growth of the XS antigen
      presenting lines has been promoted by co-culturing with gamma-irradiated NS
      cells, and this activity could be replaced with NS cell-conditioned media alone,
      but not with paraformaldehyde-fixed NS cells. Each clone derived from the NS01
      line secreted XS cell-growth-promoting activity, and this activity was blocked by
      monoclonal antibodies against colony-stimulating factor-1 receptors. Dermal
      fibroblasts also promoted the growth of XS cells in a colony-stimulating factor-1
      dependent manner. By contrast, culture supernatants from other cell lines derived
      from skin (e.g., Pam 212 keratinocytes, 7-17 dendritic epidermal T cells, or XS
      lines) failed to promote XS cell growth. These results indicate that NS cells
      belong to the fibroblast lineage and that they share the intrinsic property to
      secrete large amounts of colony-stimulating factor-1 with dermal fibroblasts.
      Dermal cells may support the growth of skin-associated antigen-presenting cells
      in vivo.

PMID- 7636306
TI  - Activation of the respiratory burst in human eosinophils by chemotaxins requires
      intracellular calcium fluxes.
AB  - Eosinophils represent major effector cells in the allergic inflammatory response.
      Following activation, these cells are capable of mediating tissue damage,
      particularly by the release of reactive oxygen species. In this study, the role
      of extracellular and intracellular calcium in the induction of the respiratory
      burst of human eosinophils was investigated in healthy non-atopic individuals.
      Pre-incubation of Fura-2-loaded eosinophils with the intracellular calcium
      chelator 2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid prevented the
      increase of the [Ca++]i following stimulation by RANTES, C5a and PAF, in
      concentration-dependent fashion, whereas depletion of extracellular calcium in
      the test medium by ethyl=eneglycol-bis(beta-aminoethyl ether)-N,N,N',N'
      tetraacetic acid was ineffective. To investigate the potential role of
      extracellular and intracellular calcium on the production of reactive oxygen
      species, flow-cytometric measurement of H2O2 production by dihydrorhodamine 123
      and lucigenin-dependent chemiluminescence were carried out. Chelation of both
      intracellular and extracellular calcium prevented production of reactive oxygen
      species after stimulation with C5a, PAF, or RANTES. However, production of
      reactive oxygen species after stimulation by phorbol myristate acetate, which
      bypasses post-receptor events by direct activation of protein kinase C, was
      prevented only after chelation of intracellular but not extracellular calcium.
      This suggested a Ca(++)-sensitive form of protein kinase C in the activation
      process of the respiratory burst. These data demonstrate that intracellular and
      extracellular calcium represent a prerequisite of chemotaxin-induced activation
      of the respiratory burst in human eosinophils. Thus, intracellular calcium seems
      to play a central role in the modulation of the respiratory burst in eosinophils
      and might therefore be an interesting target for drugs that interfere with
      calcium homeostasis and reduce the tissue destructive power of eosinophils.

PMID- 7636307
TI  - Ganglioside GT1b inhibits keratinocyte adhesion and migration on a fibronectin
      matrix.
AB  - Highly sialylated gangliosides have been shown to alter cellular adhesion to a
      fibronectin matrix. The effect of these gangliosides on the adhesion, spreading,
      and migration of cultured keratinocytes on a fibronectin matrix has not been
      explored. Ganglioside GT1b significantly prevented attachment of keratinocytes to
      fibronectin and also detached previously adherent keratinocytes in a
      concentration-dependent manner without cell toxicity. GT1b did not affect
      adhesion of keratinocytes to wells coated with laminin, type I or type IV
      collagen, 804G extracellular matrix, or albumin. GT1b also inhibited keratinocyte
      migration on fibronectin in a concentration-dependent manner at concentrations as
      low as 5 nM GT1b, but had no effect on migration of keratinocytes plated on other
      matrices. GT1b binds to intact fibronectin and to the 120-kD RGDS-containing cell
      binding fibronectin fragment, but not to the heparin- or gelatin-binding
      fragments of fibronectin. Although RGDS competes with GT1b in inhibiting
      adhesion, GT1b does not diminish binding of keratinocytes to a derivatized RGDS
      substratum, suggesting that the GT1b effect involves a non-RGDS site in the cell
      binding region that modulates RGDS/alpha 5 beta 1 integrin receptor interaction.
      Through a specific effect on keratinocyte interaction with fibronectin, GT1b may
      participate in the regulation of cell adhesion and migration on a fibronectin
      substratum, which are important events during wound healing and the spreading of
      cutaneous neoplasia.

PMID- 7636308
TI  - Tamoxifen and quercetin interact with type II estrogen binding sites and inhibit
      the growth of human melanoma cells.
AB  - The mechanism of the antiproliferative activity of tamoxifen on melanoma cells in
      vitro and in vivo is poorly understood, as it is not mediated by the
      antiestrogenic properties of tamoxifen. Using a whole-cell assay and nuclear and
      cytosolic radio-binding experiments with [3H]-estradiol as tracer, we found that
      MNT1, M10, and M14 melanoma cell lines as well as primary tumors expressed type
      II estrogen binding sites that bind tamoxifen and the flavonoid quercetin with
      similar affinity (KD 10-25 nM). Cell count and clonogenic assay showed both
      compounds to inhibit melanoma cell growth in a concentration-dependent manner in
      the range of concentrations between 1 nM and 1 microM. Neither the pure
      antiestrogen ICI-182780 nor the 3-rhamnosylglucoside of quercetin, rutin, bound
      to type II estrogen binding sites or inhibited cell growth. Our results
      suggesting that tamoxifen and quercetin can inhibit melanoma cell growth by
      interacting with type II estrogen binding sites help explain the reported
      effectiveness of tamoxifen, particularly in estrogen-receptor-negative tumors,
      and stress the potential role of quercetin in the treatment of melanoma.

PMID- 7636309
TI  - Degree of ultraviolet-induced tortuosity of elastic fibers in rat skin is age
      dependent.
AB  - To elucidate differential effects of ultraviolet (UV) exposure on three
      dimensional networks of elastic fibers during maturation of rat skin, Sprague
      Dawley rat hind limbs were irradiated with suberythemal doses of UV light (UVB,
      130 mJ/cm2, or UVA, 27 J/cm2) in three different time courses of exposure: 3-9
      weeks old, 9-15 weeks old, and 3-15 weeks old. Three-dimensional arrangement with
      special reference to linearity of elastic fibers was quantified by image analysis
      using a scanning electron microscope after a combination of intravascular resin
      injection and selective digestion technique using formic acid. Among the three
      irradiation groups, the group irradiated with UVB or UVA between 3 and 15 weeks
      old (UVB, three times per week; UVA, five times per week) elicited the most
      marked decrease in the linearity of elastic fibers. Despite the same irradiation
      period, there was a significant difference in the decreased linearity between the
      two irradiation groups of 3-9 and 9-15 weeks old, with the former irradiation
      group exhibiting greater loss of linearity than the latter irradiation group. The
      magnitude of the decreased linearity was greater in the UVB-exposed groups than
      in the UVA-exposed group. These findings indicate that the three-dimensional
      linearity of elastic fibers is more susceptible to disruption by UV exposures
      during the growth period than that after the growth period.

PMID- 7636310
TI  - Comparison of melanocytes and keratinocytes in ultraviolet-induced DNA damage per
      minimum erythema dose sunlight: applicability of ultraviolet action spectra for
      risk estimates.
AB  - Action spectra are being used in risk estimates for ultraviolet (UV) damage. The
      purpose of our investigation was to compare the susceptibility of cultured
      melanocytes and keratinocytes to UV-induced DNA damage per minimum erythema dose
      (MED) and to determine whether the predictions made with action spectra agree
      with the damage actually induced. Genetic damage was measured as the number of T4
      endonuclease V-sensitive sites (ESS). Predictions made with the action spectrum
      for the induction of DNA damage in melanocytes after irradiation with sunlight
      and a solar simulator were 15.9 and 13.2 ESS per 10(8) daltons per MED,
      respectively; with the action spectrum for the induction of DNA damage in
      keratinocytes the predictions were 12.1 and 9.8 ESS per 10(8) daltons per MED,
      respectively. To determine the actual damage per MED, cultured cells were
      irradiated with sunlight or a solar simulator, and MED was determined with an
      erythema UV meter. The induction of DNA damage in melanocytes after sunlight and
      solar simulator irradiation was 8.01 and 6.7 ESS per 10(8) daltons per MED,
      respectively, and in keratinocytes 7.49 and 7.12 ESS per 10(8) daltons per MED,
      respectively. This was considered to be in agreement with the predicted data. The
      use of action spectra for risk estimates in melanocytes appears justified.

PMID- 7636311
TI  - A monoclonal antibody to cis-urocanic acid prevents the ultraviolet-induced
      changes in Langerhans cells and delayed hypersensitivity responses in mice,
      although not preventing dendritic cell accumulation in lymph nodes draining the
      site of irradiation and contact hypersensitivity responses.
AB  - Ultraviolet B (UVB) irradiation of C3H mice causes suppression of delayed
      hypersensitivity and contact hypersensitivity (CH) to antigens encountered
      following exposure, and is accompanied by a reduction in Langerhans cell (LC)
      numbers in the epidermis, loss of epidermal antigen-presenting cell function, and
      accumulation of dendritic cells in lymph nodes draining the site of irradiation.
      Various photoreceptors and mediators of these changes have been proposed, one of
      which is cis-urocanic acid (cis-UCA) formed from the naturally occurring trans
      UCA in the epidermis on UV irradiation. A monoclonal antibody that reacts with
      cis-UCA has become available recently and has been used in this study to clarify
      the role of UCA. Pretreatment of C3H mice with the monoclonal antibody abrogated
      the UVB-induced and cis-UCA-induced reduction in epidermal LC numbers. It also
      prevented the UV-induced suppression of epidermal antigen-presenting cell ability
      as measured by the mixed skin lymphocyte response. However, it had no effect on
      the accumulation of dendritic cells in lymph nodes draining the site of UV
      exposure. With regard to hypersensitivity responses, it did not prevent UV
      induced suppression of CH to oxazolone at a range of concentrations but it
      restored to normal the UV-suppressed delayed hypersensitivity to herpes simplex
      virus, if administered before exposure. Thus cis-UCA is involved in some UV
      induced changes in murine skin but not in others, where alternative mediators,
      such as tumor necrosis factor-alpha, may be more important.

PMID- 7636313
TI  - Up-regulation of p21WAF1/CIP1 in psoriasis and after the application of irritants
      and tape stripping.
AB  - p21WAF1/CIP1 is a nucleoprotein that was initially characterized by its ability
      to be regulated transcriptionally by p53 and by its ability to mediate growth
      arrest by binding to cyclin-dependent kinases. Although p21WAF1/CIP1 is thought
      to mediate the effects of p53 in causing growth arrest, p21WAF1/CIP1 is also
      regulated in a p53-independent manner, e.g., during terminal differentiation of
      some cell lines. Growth factors including epidermal growth factor also induce
      p21WAF1/CIP1 through p53-independent pathways. Because the epidermal growth
      factor signaling pathway is abnormal in psoriatic epidermis, we studied
      p21WAF1/CIP1 expression, using in situ hybridization and immunohistochemistry, in
      psoriasis. Both p21WAF1/CIP1 mRNA and protein were significantly elevated in
      untreated psoriatic plaques compared with uninvolved psoriatic skin (p < 0.0001),
      with the up-regulation of p21WAF1/CIP1 being predominantly suprabasal. This
      increase was accompanied by a small increase in p53 protein expression of
      uncertain significance. Furthermore, p21WAF1/CIP1 expression was induced in skin
      after sellotape stripping and by the application of agents, such as dithranol,
      that are capable of inducing hyperproliferation. The pattern of p21WAF1/CIP1
      expression observed is consistent with a role in induction and maintenance of
      differentiation. Our experiments, however, cannot determine whether the
      abnormalities of p21WAF1/CIP1 epidermal expression in psoriasis and after insult
      are independent of changes in p53 expression.

PMID- 7636312
TI  - Ultraviolet radiation activates the human elastin promoter in transgenic mice: a
      novel in vivo and in vitro model of cutaneous photoaging.
AB  - The major alteration in photoaged skin is the deposition of massive amounts of
      abnormal elastic material, termed solar elastosis. In previous work, it has been
      shown that solar elastosis is accompanied by increased abundance of elastin and
      fibrillin mRNAs and upregulation of elastin promoter activity. Using a transgenic
      mouse line, which expresses the human elastin promoter, linked to a
      chloramphenicol acetyltransferase reporter gene, in a tissue-specific and
      developmentally regulated manner, we investigated the effects of ultraviolet A
      radiation and ultraviolet B radiation on human elastin promoter activity in vivo
      and in vitro. Irradiation of mice with a single dose of ultraviolet B radiation
      (491.4 mJ/cm2) resulted in an increase up to 8.5-fold in promoter activity,
      whereas a more modest increase of 1.8-fold was measured with ultraviolet A
      radiation (38.2 J/cm2). In addition, in vitro studies revealed over a thirtyfold
      increase in elastin promoter activity in response to ultraviolet B radiation (5.5
      mJ/cm2), whereas no change was measured in response to ultraviolet A radiation
      (2.2 J/cm2). These results confirm the role of ultraviolet B radiation in elastin
      promoter activation in photoaging, and identify ultraviolet A radiation as a
      contributing factor. This system should serve as a useful in vivo and in vitro
      model to study cutaneous photoaging, and for testing compounds that may protect
      against cutaneous photodamage.

PMID- 7636314
TI  - Significant correlation between connective tissue growth factor gene expression
      and skin sclerosis in tissue sections from patients with systemic sclerosis.
AB  - The role of some growth factors and cytokines in the pathogenesis of systemic
      sclerosis (SSc) has been suggested. In particular, the contribution of
      transforming growth factor beta in the progression of skin sclerosis is
      suspected. Connective tissue growth factor (CTGF) was originally identified in
      human umbilical vein endothelial cells, and a recent study has revealed that
      human skin fibroblasts produce CTGF after stimulation with transforming growth
      factor beta. In the present study, the distribution of CTGF gene expression in
      tissue sections from patients with SSc was investigated by digoxigenin-labeled in
      situ hybridization. Strong CTGF mRNA signals were observed in the fibroblasts in
      sclerotic lesions, especially in the deep dermis, of the skin specimens from
      patients with SSc, whereas there was no expression in the skin from normal
      controls. The number of fibroblasts with positive hybridization signals was more
      abundant in the dermis from the sclerotic stage than in that from the
      inflammatory stage. Our findings indicate a correlation between CTGF gene
      expression and skin sclerosis and support the hypothesis that transforming growth
      factor-beta plays an important role in the pathogenesis of SSc, because
      transforming growth factor beta is the only inducer for CTGF identified to date.

PMID- 7636315
TI  - Time-resolved infrared ATR measurements of liposome transport kinetics in human
      keratinocyte cultures and skin reveals a dependence on liposome size and phase
      state.
AB  - A novel in vitro method for studying the permeation kinetics of superficially
      applied liposomes or vesicles through layers of human skin or keratinocytes on a
      solid support is presented, employing attenuated total reflection infrared
      spectroscopy. The method is applied to investigate transport kinetics of
      unilamellar vesicles of dimyristoylphosphatidylcholine (DMPC) through cultured
      human keratinocyte layers and through human skin. We find a strong resemblance of
      the qualitative features of the permeation kinetics of small unilamellar DMPC
      vesicles for skin and keratinocytes. Detailed studies of the vesicles transport
      through keratinocyte layers show that DMPC vesicles with an average diameter of
      55 nm can readily permeate through the layer at 37 degrees C with a diffusion
      constant of D = (4.0 +/- 0.8) x 10(-15) m2/second, whereas larger vesicles of
      twice that diameter do not permeate at all. In contrast, liposomes containing a
      chemical permeation enhancer permeate through the layer significantly faster [D =
      (7.0 +/- 0.5) x 10(-15) m2/second] than the small DMPC vesicles despite their
      five-times-larger diameter. Moreover, the transport of the DMPC vesicles depends
      drastically on their phase state. No permeation was observed for small DMPC
      vesicles at a temperature of 10 degrees C when the lipid is in the crystalline
      phase state. Our results indicate that keratinocyte culture layers can pose a
      significant permeation barrier for vesicles. The permeation mechanism can be
      explained by diffusion of the vesicles through small pores and gaps in the layer,
      presumably driven by transdermal osmotic gradients.

PMID- 7636316
TI  - Lipids are covalently attached to rigid corneocyte protein envelopes existing
      predominantly as beta-sheets: a solid-state nuclear magnetic resonance study.
AB  - C solid-state nuclear magnetic resonance at natural abundance was used to study
      isolated corneocyte envelopes from porcine stratum corneum. The presence of
      lipids covalently attached to the protein envelopes was detected by chemical
      shifts of methylene and methyl groups of the bound lipids. The corneocyte protein
      envelopes are rigid, as suggested by efficient 1H to 13C cross polarization and
      13C spin-lattice relaxation studies. The chemical shift of the carbonyl carbons
      of the protein envelopes supports the prediction that the chemically bound lipid
      envelope is attached to proteins arranged predominantly in the beta-sheet
      conformation, allowing a dense palisade of ceramide molecules to form a water
      impermeable external sheath.

PMID- 7636317
TI  - Divalent cations control cell-substrate adhesion and laminin expression in normal
      and malignant human melanocytes in early and late stages of cellular
      differentiation.
AB  - Integrins are a class of adhesion molecules that depends on divalent cations for
      proper function. This study examined whether human normal melanocytes and
      malignant (metastatic) melanocytes with early and late stages of cellular
      differentiation (G361 and SK-MEL-23, respectively) would differ in integrin
      mediated adhesion to fibronectin, laminin, as well as collagens type I and type
      IV, and whether divalent cations could influence the strength of adhesion
      ability. Integrin subunit expression was determined by flow cytometry using
      integrin subunit-specific antibodies as probes. Integrin-specific adhesion was
      determined using soluble glycine-arginine-glycine-asparagine-serine peptide and
      integrin subunit-specific antibodies as functional blocking agents. This study
      shows that both normal and malignant melanocytes adhere to extracellular matrices
      in a divalent cation-dependent manner, and adhesion strength varies with the
      cation species. Integrins can be rapidly activated by small alterations in cation
      concentration, manganese being the most potent. There were marked differences in
      substrate adhesion between normal melanocytes and metastatic malignant melanoma
      cells, but these differences were not related to the stage of cellular
      differentiation. All the three cell types, however, expressed the same integrin
      subunits at approximately the same levels. This suggests that substrate adhesion
      of melanocytes and melanoma cells might involve some integrin-independent
      mechanisms as well. Manganese, in particular, appears to cause adhesion by
      activating both integrin-dependent and -independent mechanisms.

PMID- 7636318
TI  - Eugene Robertson Special Lecture. Hyperthermia from the clinic to the laboratory:
      a hypothesis.
AB  - Recently reported thermal isoeffective dose-response relationships in human
      tumours confirm the existence of an effect of hyperthermia in combination with
      radiotherapy. The prognostically important thermal doses are based upon the
      lowest temperatures achieved within tumours, and these thermal doses are well
      below those used in most laboratory studies that have provided the rational for
      hyperthermia treatment. Direct thermal cytotoxicity and thermal
      radiosensitization are insignificant at these low thermal doses. Other
      explanations for the mechanism of hyperthermia effect appear warranted. We
      hypothesize that hyperthermia at low thermal doses causes reoxygenation and hence
      direct radiosensitization in vivo.

PMID- 7636319
TI  - Status of hyperthermic oncology in Europe: results of an ESHO survey.
AB  - ESHO members were surveyed by questionnaires regarding their activities in
      clinical and experimental hyperthermic oncology. There were 67 replies from a
      total of 12 countries and 53 cancer centres. Half of all respondents were
      involved both in experimental and clinical hyperthermia and more than 70% longer
      than five years. Most centres treated less than three patients per month and
      included only few patients in phase III and multicentre studies. More than 80% of
      the respondents expected clinical hyperthermia to be a part of routine oncology
      in the future and most to be given with a curative intent. Only few respondents
      spent more than 25% of their working time in hyperthermia and only very few
      departments used more than 5% of their total activities in hyperthermia.
      Financial granting seemed stable and most were optimistic for the forthcoming
      financial support. Experimentally more than 80% expected still to be involved in
      hyperthermic research in three years. The survey indicated that too many centres
      spent too little time in clinical hyperthermia and that more patients need to be
      included in phase III and multicentre studies.

PMID- 7636320
TI  - Cytokine production ex vivo: effect of raised body temperature.
AB  - This study was designed to examine the effects of hyperthermia in humans on the
      production of interleukin (IL)-1 alpha, IL-1 beta, tumour necrosis factor
      (TNF)beta and interferon (IFN)gamma, determined in supernatants from in vitro
      lipopolysaccharide or phytohemagglutinin stimulated blood mononuclear cells
      (BMNC), including the effect of indomethacin in the assays on these cytokines.
      Eight healthy volunteers were immersed into a hot water bath (water temperature
      39.5 degrees C) for 2 h, during which their rectal temperature rose to 39.5
      degrees C. On a later day they served as their own controls, being immersed into
      thermoneutral water (34.5 degrees C) for 2 h. Blood samples were collected
      before, at body temperatures of 38, 39 and 39.5 degrees C, and 2 h after water
      immersion and at corresponding time points in the control experiment.
      Hyperthermia did not influence the production of cytokines from stimulated BMNC.
      Indomethacin in the assays significantly enhanced the ex vivo production of TNF
      beta at hyperthermic and thermoneutral conditions; this indomethacin enhanced
      production of TNF beta declined from pre-value in the hyperthermia experiment
      compared to the control experiment. Furthermore, indomethacin augmented the
      production of IFN gamma from stimulated BMNC both in the hyperthermic and the
      control experiments; the indomethacin effect was, however, not different at the
      two conditions. It is suggested that hyperthermia alters the sensitivity of BMNC
      to prostaglandins.

PMID- 7636322
TI  - Predictive factors for skin reactions in patients treated with
      thermoradiotherapy.
AB  - In this study we performed univariate analyses to analyse the predictive factors
      for skin reactions, i.e. erythema, thermal blisters and ulceration, that occur
      during thermoradiotherapy. One hundred and twenty-six fields in 126 patients were
      treated with thermoradiotherapy using 915 MHz external microwave hyperthermia.
      Mean age of patients was 62 years. All but 11 lesions received previous therapy.
      Prior treatment included surgery (75%), chemotherapy (60%) and/or radiation
      therapy (51%). The mean previous radiation dose was 54 +/- 2 Gy. The concurrent
      tumour radiation dose was 45 +/- 1 Gy, in 16 fractions, over 35 elapsed days
      (dose per fraction of 1.6-4.8 Gy). The mean number of heat sessions administered
      was 5.5 +/- 0.2 (range 1-14). In 83% of cases hyperthermia was administered
      biweekly. Forty-two patients were treated without any skin reaction (33%),
      erythema occurred in 59 fields (47%), transient thermal blisters occurred in 25
      fields (20%) and ulceration occurred in 23 fields (18%). In 25 cases, two or more
      skin reactions (20%) were observed concurrently. Concurrent radiation dose
      correlated with skin reactions (p = 0.02). The incidence of skin reactions was
      inversely correlated with previous radiation therapy (p = 0.04) and previous
      radiation therapy dose (p = 0.04) possibly due to fibrosis. None of the tumour or
      skin thermal parameters correlated with the reaction rate.

PMID- 7636321
TI  - Prognostic factors for tumour response and skin damage to combined radiotherapy
      and hyperthermia in superficial recurrent breast carcinomas.
AB  - Prognostic factors for complete tumour response and acute skin damage to combined
      hyperthermia and radiotherapy were analysed in material of patients with breast
      cancer, recurrent in previously irradiated areas. Radiotherapy was given daily to
      a total absorbed dose of 30.0 Gy in 2 weeks or 34.5 Gy in 3 weeks. The first
      radiotherapy schedule was combined with heat twice weekly, a total of four heat
      treatments (schedule A). The second radiotherapy schedule was combined with heat
      either once or twice a week resulting in a total of three (schedule B) or six
      (schedule C) heat treatments. Heat was induced with microwaves (2450, 915 or 434
      MHz) via external applicators and always given after the radiotherapy fraction.
      The complete response (CR) rate in evaluable patients was 71% (49/69). There was
      no significant difference in CR rate between the three different hyperthermia
      schedules. The CR rates were 74% (14/19), 65% (15/23) and 74% (20/27) for
      schedules A, B and C respectively. The only factor predicting CR, evaluated both
      uni- and multivariately, was the CRE-value for the present radiotherapy dose (p =
      0.02). If only tumours treated with 915 MHz were taken into account, however,
      then the highest minimum temperature at a given heat session predicted complete
      response (p = 0.03). This was true also in a multivariate analysis of this
      subgroup of tumours. A Kaplan-Meier analysis (log rank test) showed no
      significant difference in duration of CR between the different treatment
      schedules. Cox's proportional hazards method revealed three significant factors:
      tumour size (negatively correlated, p = 0.007), the time interval between the
      diagnosis of the primary tumour and the present treatment (p = 0.02) and the
      average temperature (0.03). Maximum acute skin reactions in the treatment field
      were scored according to an ordinal scale of 0-8, modified after WHO 1979. Twenty
      six treatment areas (32%) expressed more severe skin damage (score > or = 5) in
      terms of desquamation with blisters (14%) and necrosis or ulceration (19%).
      Factors correlated with skin damage were the size of the lesion area (p = 0.011),
      the highest average maximum temperature during a given heat session (p = 0.03)
      and the fractionation schedule of hyperthermia (p = 0.05). The extent of previous
      radiotherapy absorbed dose, previous surgery in the treated area or previous
      chemotherapy had no significant influence on the acute skin reactions.

PMID- 7636323
TI  - Clinical results of thermoradiotherapy for soft tissue tumours.
AB  - Thirty-one unresectable and/or recurrent soft tissue tumours in 27 patients
      underwent hyperthermia in combination with radiation therapy. Locoregional
      hyperthermia was administered once or twice a week for 40-60 min to a total of 2
      14 sessions using RF capacitive or microwave heating equipment. Radiation therapy
      was given 10-20 min before hyperthermia at doses of 20.8 to 70 Gy. The mean +/-
      SD of the maximum, average, and minimum intratumour temperatures was 44.0 +/- 2.9
      degrees C, 42.3 +/- 1.6 degrees C, 40.1 +/- 1.1 degree C respectively, and that
      of the percentage of the intratumour points that exceeded 41 and 43 degrees C was
      66.0 +/- 33.6, and 31.0 +/- 26.1 respectively. Of the 31 tumours treated, 13
      (42%) showed CR (complete regression), 10 (32%) PR (> 50 and < 100% regression)
      and 8 (26%) NC (< 50% regression). Since intratumour low density areas on post
      treatment CT scans have been demonstrated to be a useful parameter for assessing
      tumour response to thermoradiotherapy, the presence of low density areas was also
      assessed. Low density areas were classified into the following three categories
      according to the percent area occupied in the maximal cross-section of the
      tumour: type I, < 50%, type II, 50-80%; type III, > 80%. Of 20 tumours evaluable,
      6 (30%) exhibited type III change, 11 (55%) type II and 3 (15%) type I. All of
      the type III tumours demonstrated a marked response on follow-up or
      histopathological examination. The major complication associated with treatment
      was skin ulcer in two patients. The five-year survival of the total 27 patients
      and 18 patients who had no distant metastases at the start of treatment was 32
      and 48% respectively. These results indicate the clinical benefit of
      thermoradiotherapy using RF capacitive or microwave equipment for locally
      advanced and/or recurrent soft tissue tumours.

PMID- 7636324
TI  - The advantageous use of hypoxic tumour cells in cancer therapy: identical
      chemosensitization by metronidazole and misonidazole at moderately elevated
      temperatures.
AB  - Chemosensitization by two nitroimidazoles (NIs), metronidazole (METRO) and
      misonidazole (MISO), of the anti-tumour effect of alkylating agents was studied
      at three different temperatures: room temperature (RT), 37 and 41.5 degrees C.
      Three alkylating agents, cyclophosphamide (CY), 1,3 bis(2-chloroethyl)-N
      nitrosourea (BCNU) and melphalan (L-PAM) were tested when the tumours reached an
      average diameter of 4 mm. Tumours were 4th generation isotransplants of a
      spontaneous fibrosarcoma, FSa-II. Treatment at 37 or 41.5 degrees C was given by
      immersing the tumour-bearing foot for 60 min in a water bath set at these
      temperatures. The test agents were injected ip immediately before immersing the
      foot in the water bath, whereas METRO or MISO (2.5 mmol/kg) was given ip 30 min
      before the injection of a test agent. Following treatment the tumour growth (TG)
      time, i.e. the time required for one-half of treated tumours to reach 1000 mm3
      after the treatment day, was studied. For CY, MISO was a better sensitizer than
      METRO at RT and 37 degrees C, but the magnitude of the chemosensitization by MISO
      and METRO became identical at 41.5 degrees C. Notably, the chemosensitization was
      substantially enhanced at 41.5 degrees C, whereas neither 41.5 degrees C-heat,
      NIs or combined NI and heat prolonged the TG time. Although no chemosensitization
      was observed for BCNU at RT, both METRO and MISO equally enhanced the effect of
      BCNU at 41.5 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7636325
TI  - Protocol for freezing thermotolerant cells and maintaining thermotolerance
      following thawing.
AB  - Two independent laboratories have demonstrated that suspension-grown, Chinese
      hamster ovary (CHO) cells can be made thermotolerant, frozen and subsequently
      thawed such that they still express thermotolerance. Thermotolerance was
      determined as the ability to protect cells against hyperthermic cell killing
      (colony formation assay) and the ability to reduce protein aggregation within the
      nuclei of heated cells. Cells were frozen either following development of full or
      partial thermotolerance. In the former case frozen cells maintained
      thermotolerance upon thawing and in the latter case cells subsequently developed
      full thermotolerance following thawing and incubation at 37.0 degrees C. After
      thawing, frozen cells displayed a temporal course of thermotolerance development
      and decay that was similar to that for never-frozen cells. Success was obtained
      using either asynchronous or synchronous cell populations, and the heat
      sensitivity of the cells was not altered by the freezing procedure. The
      experimental results demonstrate the plausibility of utilizing a frozen stock of
      thermotolerant cells to make thermotolerance experiments more convenient.

PMID- 7636326
TI  - Inspired anaesthetic gas humidification improves thermal uniformity during canine
      whole body hyperthermia.
AB  - Supplying warmed saturated water vapour in anaesthetic gases during whole body
      hyperthermia (WBH) could potentially improve thermal uniformity in the trachea
      and esophagus. Four normal dogs were anaesthetized for WBH at 42 degrees C. A
      Puritan Bennett Cascade humidifier was used to supply anaesthetic gases saturated
      with water vapour at an average airway temperature of either 42 degrees C or 38
      degrees C. Esophageal temperature was monitored at the thoracic inlet and 5 cm
      cephalad. Thermal dose was estimated by calculating equivalent minutes for an
      isoeffect at 43 degrees C (CEM 43 degrees Tx, where Tx is the site of temperature
      measurement). Endotracheal mucociliary transport velocity (MCTV) was determined
      before and 48 h following WBH by 99mTc-MAA scintigraphy. Compared to the 38
      degrees C humidified gas group, dogs receiving 42 degrees C humidified gas
      reached 42 degrees C faster (p = 0.02) and had CEM 43 degrees T(esophageal)
      values equivalent to the target CEM 43 degrees T(rectal). Endotracheal MCTV with
      42 degrees C humidified gas, however, was reduced 53% from baseline 48 h
      following WBH (p = 0.02). With 38 degrees C humidified gas, endotracheal
      mucociliary transport velocity was unchanged from baseline 48 h post WBH.
      Tracheal histology was examined using light and electron microscopy in four
      additional dogs euthanatized following 90 min of 42 degrees C humidified gas
      combined with WBH. There was no histological evidence of tracheal or lung thermal
      damage with 42 degrees C humidified gas in these four dogs. However, a moderate
      increase in tracheal goblet cell secretory granule staining was observed. This
      change could imply temporary heat-induced ciliary microtubule dysfunction, rather
      than decreased mucus production, as the likely mechanism of reduced mucociliary
      transport velocity 48 h following WBH. Administration of 42 degrees C humidified
      anaesthetic gases with WBH improves heating rate and esophageal thermal
      uniformity but temporarily depresses tracheal mucociliary transport velocity.

PMID- 7636327
TI  - Verification of a hyperthermia model method using MR thermometry.
AB  - Simulation of hyperthermia induced power and temperature distributions is
      becoming generally accepted and finding its way into clinical hyperthermia
      treatments. Such simulations provide a means for understanding the complete three
      dimensional temperature distribution. However, the results of the simulation
      studies should be regarded with caution since modelling errors will result in
      differences between the actual and simulated temperature distribution. This study
      uses a diffusion weighted magnetic resonance (MR) based technique to measure
      hyperthermia induced temperature distributions in a three-dimensional space in a
      non-perfused phantom. The measured data are used to verify the accuracy of
      numerical simulations of the same three-dimensional temperature distributions.
      The simulation algorithm is a finite element based method that first computes the
      electromagnetic induced power deposition then the temperature distribution. Two
      non-perfused phantom studies were performed and qualitatively the MR and
      simulated distributions agreed for steady-state. However, due to the long MR
      sampling time (approximately 4 min), poor agreement between the simulations and
      MR measurements were obtained for thermal transients. Good agreement between the
      simulations and fibreoptic thermometry measurements were obtained. The fiberoptic
      measurements differed from the simulations by 0.11 +/- 0.59 degrees C and -0.17
      +/- 0.29 degrees C (mean +/- standard deviation for the two studies).

PMID- 7636328
TI  - Patterns of changes of tumour temperatures during clinical hyperthermia:
      implications for treatment planning, evaluation and control.
AB  - The patterns of changes in tumour temperatures were studied at selected times
      throughout 104 hyperthermia sessions. Temperature change patterns were analysed
      in the context of the known patterns of change of the applied power. First, of 69
      extracranial treatments analysed, 74% indicated relatively flat temperatures at
      constant applied power during a major portion of the treatment, thereby
      indicating that during that time there were no major changes in any of the
      physical or physiological tissue parameters which contribute to the ability of
      the tumour tissue to remove energy (Pattern 1). Second, after reaching an initial
      steady state, approximately 14% of these extracranial treatments showed either
      steadily decreasing temperatures at constant power, or constant temperatures at
      steadily increasing applied power, thereby indicating that the tumour's ability
      to remove energy was steadily increasing in time following the initial steady
      state (Pattern 2). Finally, after reaching an initial steady state, the remaining
      12% of these treatments showed a pronounced decrease in temperature occurring
      about 10-20 min into the treatment followed by increasing temperatures or
      levelling off of temperatures at a higher value than the temperature minimum that
      had occurred, all at constant applied power (Pattern 3). Of 35 brain treatments
      analysed, 80% followed Pattern 1, 14% followed Pattern 2, and 6% followed Pattern
      3. Intratumoral heterogeneity was evident in some cases with approximately 44% of
      all treatments having at least one individual temperature sensor change in a
      manner that did not follow the average direction of change when all sensors were
      combined. For seven patients with permanent probes, the patterns of change
      presented in the first treatments were also observed during six out of seven of
      the second treatments. In addition, three out of the five patients who had an
      evaluable third treatment showed a pattern of change during that third treatment
      that was similar to the pattern observed in both treatment one and treatment two.

PMID- 7636329
TI  - The development of a high impedance all ceramic thermistor resistant to microwave
      irradiation: its possible medical application.
AB  - We developed a prototype all ceramic thermistor (ACT) composed of a silicon
      carbide (SiC) ceramic thermistor and SiC ceramic fibre-lead wires in order to
      accurately measure tissue temperature during microwave heating treatment. High
      density SiC ceramics reflects electromagnetic waves and manifests microwave
      resistant properties. The resistance of the SiC ceramic thermistor is
      approximately 15 M Ohm at 20 degrees C and has a sensitivity of approximately 200
      K Ohm/ degrees C. SiC ceramic fibre resistance is approximately 40 K Ohm/cm,
      whereas its sensitivity is approximately 10 Ohm/ degrees C-cm, significantly
      lower than that of the SiC ceramic thermistor. The resistance of the SiC ceramic
      fibre is stable. This enables the ACT to be designed with the two-probe method
      instead of the four-probe method which was adopted in the Bowman type thermistor,
      resulting in a greatly simplified model. The measurement error caused by the
      temperature dependence of SiC ceramic fibre is < 0.02 degrees C. The ACT was
      inserted into muscle-equivalent agar phantom and into gluteal muscles of rabbits,
      and microwave irradiation was carried out. We recorded the phantom and tissue
      temperature without disturbance by the electromagnetic field for heating. This
      prototype ACT appears promising for its possible clinical applications in such
      settings as hyperthermic cancer therapy in man.

PMID- 7636330
TI  - Comment on the hypothesis that hyperthermia facilitates reoxygenation.

PMID- 7636331
TI  - Chemosensitization at elevated temperatures.

PMID- 7636332
TI  - [An objective measurement of softening of uterine cervix using tactile sensor for
      hardness].
AB  - The authors studied an objective measurement for cervical softening by means of a
      tactile sensor equipped with a piezoelectric swing element made from ceramic. The
      hardness of objects was indicated by changes in frequency (delta f) measured by
      this sensor. The authors measured the hardness of cervixes in 66 (non pregnant,
      pregnant, delivering and postpartum) Sprague-Dawley rats with the sensor. After
      the measurement of delta f, the rats' cervixes were removed, and the ratios of
      their dry weight to wet weight (weight-ratio) and hydroxyproline contents were
      measured. The delta f of rats' cervixes increased during pregnancy and became
      maximum at delivery. The weight-ratio also increased and correlated with delta f
      (r = 0.812). The hydroxyproline content decreased during pregnancy and correlated
      with delta f (r = 0.674). The hardness of the cervixes of 26 non pregnant and 192
      pregnant women and their Bishop scores were also measured. The delta f of
      pregnant women's cervixes increased significantly in comparison with those of non
      pregnant women. The delta f of cervixes in primiparas correlated with the
      progress of pregnancy (r = 0.408). A moderate correlation between the delta f of
      cervixes and Bishop scores was also observed in the pregnant women. These results
      show that the tactile sensor may be able to be used in the objective measurement
      of hardness of the uterine cervix.

PMID- 7636333
TI  - [Studies on coagulation-fibrinolysis during normal pregnancy, labor and
      puerperium using recently developed molecular markers].
AB  - The purpose of this study is to further investigate physiologic changes in plasma
      coagulation-fibrinogenolysis and fibrinolysis in the utero-placental circulation
      in normal pregnancy, labor and puerperium, employing newly developed molecular
      markers for coagulation-fibrinogenolysis and fibrinolysis such as prothrombin
      fragment 1 + 2 (F1.2), active PAI-1, Fgfr and Fbfr. In 30 non-pregnant women and
      20 normal pregnant women, the levels of plasma F1.2, TAT, FPA, Fgfr and active
      PAI-1 were noticeably increased from the first trimester to the full term.
      tPA/PAI-1/C and B beta 15-42 were also increased as gestation advanced. These
      findings suggested that noticeably activated states of coagulation,
      fibrinogenolysis and fibrinolysis exist in normal pregnancy. In 30 cases of
      placental circulation in healthy pregnant women and at 20-30 minutes after
      uteroplacental separation, the levels of plasma F1.2, TAT, FPA, tPA/PAI-1/C, PIC,
      B beta 15-42, Fgfr and Fbfr were noticeably increased, and the level of active
      PAI-1, was noticeably decreased in the uterine venous blood as compared with
      those of the peripheral venous blood in healthy pregnant women. At 20-30 minutes
      after utero-placental separation in the uterine venous blood and in peripheral
      venous blood, the changes in the levels of these markers were significantly
      increased, whereas active PAI-1 and PI were significantly depressed compared with
      those in healthy pregnant women. These findings suggest that further enhancement
      of local coagulation-fibrinolysis occurred in utero after separation of the
      placenta.

PMID- 7636334
TI  - [Development of the monoclonal antibody to cultured uterine endometrial
      adenocarcinoma cells (EI)].
AB  - A new monoclonal antibody (Moab), 3H2, was produced by immunizing Balb/C mouse
      with EI, a newly established human cell line from moderately differentiated
      endometrial adenocarcinoma of the uterus. The molecular weight of the Moab 3H2
      defined antigen was 36,000 daltons, and suggests that the epitope of the Moab 3H2
      defined antigen was protein moiety. Moab 3H2 was of the IgG1, subclass. Using
      formalin-fixed, paraffin-embedded human tissues and immunohistochemical
      techniques (ABC method), Moab 3H2 has demonstrated reactivity, Moab 3H2 reacted
      with well and moderately differentiated endometrial adenocarcinoma of the uterus,
      but did not react with poorly differentiated endometrial adenocarcinoma of the
      uterus, Moab 3H2 did not react with other tissues, malignant or normal, except
      ovarian clear cell adenocarcinoma, suggesting that Moab 3H2 reacts with well and
      moderately differentiated endometrial adenocarcinoma of the uterus with high
      specificity. To analyze the epitope of the Moab 3H2-defined antigen, it should be
      useful to make clear the function of carcinogenesis, differentiation and growth
      of endometrial adenocarcinoma of the uterus.

PMID- 7636335
TI  - [Post-operative peritoneal washing cytology in cases of stage IIIa endometrial
      carcinoma with positive peritoneal cytology].
AB  - According to the new FIGO staging of corpus cancer, the cases with positive
      peritoneal cytology alone belong in stage IIIa. The authors previously reported,
      however, good prognosis of IIIa cases with only positive peritoneal cytology. In
      order to assess the potential of malignant cells in the peritoneal cavity to
      metastasize, post-operative peritoneal washing cytology was undertaken. This
      study was conducted on a total of 115 consecutive patients with endometrial
      carcinoma who underwent primary surgical therapy at the Cancer Institute Hospital
      during the 25-month period from December, 1991 to December, 1993. Fifteen cases
      were included in stage IIIa with positive intraoperative peritoneal cytology
      alone. In 12 cases with endometrioid adenocarcinoma, a Silascon tube was indwelt
      in the abdominal cavity before closure of the abdomen. The peritoneal cavity was
      washed with 500 ml of physiological saline through the indwelt tube 14 days after
      the operation. The cytology of recovered washings was negative in all cases. Only
      two cases received postoperative chemotherapy owing to other prognostic factors.
      These 12 cases are alive with no evidence of disease after 12 to 36 months. The
      present study demonstrated that malignant cells in the peritoneal cavity appear
      to have a very low potential for implantation into the peritoneum.

PMID- 7636336
TI  - [The accuracy of computed tomography and magnetic resonance imaging in evaluating
      the extent of endometrial carcinoma].
AB  - The present study was designed to determine the accuracy of Computed Tomography
      (CT) and Magnetic Resonance Imaging (MRI) in evaluating the extent of the tumor
      in 36 patients with endometrial carcinoma. The CT and MRI findings were compared
      with the microscopic pathologic characteristics in all cases. Linear regression
      analysis for measurements of residual normal myometrium revealed significant
      positive correlations (p < 0.001) between MRI (r = 0.861) and CT (r = 0.826)
      findings and pathologic evaluation. Thirty-six patients were divided into two
      groups according to our previous CT and MRI criteria: the superficial myometrial
      invasion group and advanced tumor group. In MRI findings, higher incidences of
      deep (> or = 1/2) myometrial invasion (p < 0.001), vessel permeation (p < 0.05)
      and cervical involvement (p < 0.05) were observed in the advanced group. In CT
      findings, deep myometrial invasion (p < 0.001) was observed in the advanced
      group. The incidence of extrauterine extension of the tumor did not differ
      significantly between CT and MRI findings. The accuracy figures for cervical
      involvement evaluated by CT and MRI were 83% and 86%, respectively. In four of 6
      patients, in whom an intact Junctional zone (j-zone) was detected by MRI, the
      tumor was localized in the endometrium. The remaining 2 patients had only
      superficial myometrial invasion histologically. In all 16 patients, in whom the j
      zone was interrupted in MRI findings, myometrial invasion was confirmed
      pathologically.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7636337
TI  - [Assessment of serum estrogen levels by RIA with HPLC during hormone replacement
      therapy].
AB  - We studied the serum estradiol and estrone levels in 146 peri and postmenopausal
      women, and in 38 women who had complained of various climacteric disturbance
      symptoms during daily hormone replacement therapy (HRT) with conjugated equine
      estrogen (CEE) 0.625 mg and medroxyprogesterone acetate (MPA) 2.5 mg. Serum
      estradiol and estrone were measured before treatment, and at 6 months, and after
      one year of the HRT therapy by HPLC-radioimmunoassay. In 146 peri and
      postmenopausal women, the serum level of estradiol was from 3 to 6pg/ml. The
      serum level of estradiol in 38 women after HRT significantly increased (p < 0.01)
      from 3.34 to 23.6 pg/ml at 6 months, and 21.5 pg/ml at 12 months. The serum level
      of estrone significantly increased (p < 0.01) from 26.6pg/ml to 156.7pg/ml at 6
      months, and 137.2pg/ml at 12 month. These results are very useful for deciding on
      the doses of hormones and the expected serum estradiol level in HRT for Japanese
      women.

PMID- 7636338
TI  - [A case of short umbilical cord syndrome].

PMID- 7636339
TI  - [A case of immunologic thrombocytopenic purpura undergoing preoperative high-dose
      immunoglobulin therapy and splenectomy at 14th week of gestation followed by a
      delivery of healthy baby].

PMID- 7636340
TI  - [Cerebral and hepatic vasospasm in a case of HELLP syndrome complicated with
      eclampsia].

PMID- 7636341
TI  - [ Variability in vertigo and syncope].

PMID- 7636343
TI  - [Definition and classification of syncope].

PMID- 7636342
TI  - [Definition and classification of vertigo].

PMID- 7636344
TI  - [Basic information necessary for management: 1. Anatomical information necessary
      in understanding vertigo].

PMID- 7636347
TI  - [Diagnosis: 2. Methods and tests for diagnosis of syncope].

PMID- 7636345
TI  - [Basic information necessary for management: 2. Types and actions of agents used
      to treat vertigo].

PMID- 7636346
TI  - [Diagnosis: 1. Methods and tests for diagnosis of vertigo].

PMID- 7636348
TI  - [Diagnostic tests: 3. Differential diagnosis of vertigo, syncope, and epilepsy].

PMID- 7636349
TI  - [Diagnostic keypoints and management: 1. Vertigo and syncope caused by
      hypotension].

PMID- 7636351
TI  - [Diagnostic keypoints and management: 3. Vertigo with indications for vascular
      reconstruction].

PMID- 7636350
TI  - [Diagnostic keypoints and management: 2. Vertigo caused by cerebrovascular
      disorder].

PMID- 7636353
TI  - [Diagnostic keypoints and management: 5. Vertigo experienced by
      otorhinolaryngological patients].

PMID- 7636352
TI  - [Diagnostic keypoints and management: 4. Syncope and vertigo caused by cardiac
      diseases].

PMID- 7636354
TI  - [Diagnostic keypoints and management: 6. Vertigo caused by brain tumor].

PMID- 7636355
TI  - [Diagnostic keypoints and management: 7. Vertigo and syncope associated with
      psychosomatic diseases].

PMID- 7636357
TI  - [Discussion: diagnosis and treatment of vertigo and syncope].

PMID- 7636356
TI  - [Vertigo caused by drugs--with special reference to ototoxicity of certain
      drugs].

PMID- 7636358
TI  - [Case of myelodysplastic syndrome associated with Behcet's disease].

PMID- 7636359
TI  - [Interstitial nephritis caused by non-steroidal anti-inflammatory agents--report
      of 2 cases].

PMID- 7636360
TI  - [Case of Cushing's syndrome associated with empty sella syndrome and anterior
      pituitary hypofunction].

PMID- 7636361
TI  - [Case of gastric leiomyoblastoma with prominent cyst formation].

PMID- 7636362
TI  - [Case of acute rhabdomyolysis caused by maintaining the same limb position for an
      extended period].

PMID- 7636364
TI  - [Case of Creutzfeldt-Jakob disease with the development of Gerstmann syndrome at
      its onset].

PMID- 7636363
TI  - [Suspected case of lupus cystitis with successful early treatment].

PMID- 7636365
TI  - [Mucosal immunity].

PMID- 7636366
TI  - [JC virus and disease onset--development of pathogenic mutant strains in the
      host].

PMID- 7636367
TI  - [Muscular sympathetic nervous activity and automatic nervous system diseases].

PMID- 7636368
TI  - Anorectal function after low anterior resection of the rectum.
AB  - Impaired neorectal function or sphincter incompetence have been respectively
      implicated as causative factors of increased frequency of defaecation or
      incontinence after low anterior resection of the rectum (LARR) for rectal
      carcinoma, although individual mechanisms of anorectal function have not been
      fully studied. Functional and laboratory results were evaluated in 19 subjects,
      who had a LARR for rectal carcinoma before and after the procedure, and were
      compared to those of normal subjects. LARR worsened anorectal function, mostly by
      significantly increasing the daily number of defaecations (p < 0.001), while
      major incontinence was reported in three cases. Patients with rectal carcinoma
      have a decreased resting anal pressure on manometry, as compared to controls (p <
      0.001). LARR further reduces anal resting pressure (p < 0.001) as well as all
      parameters that express internal sphincter activity, such as presence and
      amplitude of either slow (p < 0.05 and p < 0.01) or ultraslow waves. LARR also
      impaired external anal sphincter activity, as expressed by the reduction in anal
      squeeze pressure (p < 0.001). Anorectal sampling was found reduced in incidence
      and frequency in LARR patients as compared to controls (p < 0.01 and p < 0.001),
      and was impaired even further postoperatively (p < 0.001). Rectoanal inhibitory
      reflex was present in all but three patients postoperative, but significantly
      impaired as compared to controls. Rectal volumes to elicit transient or permanent
      desire to defecate, maximal tolerable rectal volume and rectal compliance were
      also significantly reduced after LARR (p < 0.001, p < 0.001, p < 0.01 and p <
      0.001 respectively). Large bowel transit was significantly enhanced after LARR (p
      < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7636369
TI  - The neurophysiological significance of perineal descent.
AB  - The establishment of a linear relationship between perineal descent (PD) and
      pudendal nerve motor terminal latency (PNMTL) is important in understanding the
      pathophysiology of pudendal neuropathy. The amount of stretching of the pudendal
      nerve resulting from the extent of PD, should correlate with the amount of injury
      sustained (PNMTL). The two key previous studies which used different techniques
      to measure PD, have differed on this vital issue. A prospective study was
      undertaken in 141 consecutive patients with PD (M:F = 57:84; mean age 46.3 SEM
      1.6 years) to clarify this discrepancy. The patients had chronic constipation
      (81), neurogenic faecal incontinence (31), rectal mucosal prolapse (17) or female
      urinary stress incontinence (9). All underwent measurements of PD (by
      perineometry), anal sphincter pressures, single fibre anal sphincter
      electromyography and PNMTL. These variables, as well as age were analyzed for a
      linear relationship with PD by multiple regression analysis. Age was the only
      independent variable predicting PD at rest (T = -3.2; p < 0.005). PNMTL was the
      only independent variable predicting PD on straining (T = -3.0; p < 0.005). In
      conclusion, a linear relationship between PD on straining and PNMTL was
      confirmed, supporting the previous study which also measured PD by perineometry.
      The other study which refuted such a relationship measured PD radiologically, and
      it is likely that the difference was in the measurement technique.

PMID- 7636370
TI  - Transanal local resection for benign and malignant rectal tumours.
AB  - Local therapy has been widely reported and accepted for benign tumours and
      carefully selected cancers of the rectum. Thirty-three patients with benign or
      malignant low rectal tumors have undergone a prospective evaluation after local
      resection with transanal electroresection as described by Faivre. Patients were
      divided in three groups: 1) local excision of benign tumours (12 patients), 2)
      curative resection for localised malignant tumours (7 patients) and 3) palliative
      local resection for malignant tumours (14 patients). The complications included
      transient incontinence and rectal bleeding. Patients have been followed for a
      mean period of 18 months (1-54). In group 3 there were four (28%) recurrences.
      The remainder of the patients with malignant tumours have been free of disease on
      follow-up. Although it is ideal for benign neoplasms, further follow-up is needed
      to determine its true indication in malignant lesions.

PMID- 7636372
TI  - "Sphincter repair".

PMID- 7636371
TI  - Incidence of colorectal cancer and all cause mortality in non-selected patients
      with ulcerative colitis and indeterminate colitis in Malmo, Sweden.
AB  - Cancer morbidity and all cause mortality were studied prospectively in all
      patients with definite and probable ulcerative colitis and indeterminate colitis
      diagnosed from 1958 to 1982, in the city of Malmo, Sweden. The follow-up to Jan.
      1, 1990 was complete for all but ten patients. Nine of the 471 patients with
      ulcerative colitis and three of the 100 patients with indeterminate colitis
      developed colo-rectal cancer. The incidence of colorectal cancer in ulcerative
      colitis was 1.4 per 1000 person-years. The observed number of cases was 2.1 times
      higher than expected; (95% C.I. 1.0-4.1), based on the age- and sex-specific
      cancer incidence in the city during the study period. Indeterminate colitis was
      associated with a higher colorectal cancer risk than ulcerative colitis; 2.4 per
      1000 person-years; (SMR 8.6, 95% C.I. 1.8-25.1). Both conditions were associated
      with a slight increased mortality rate, for ulcerative colitis 12.6 per 1000
      person-years; (SMR 1.3, 95% C.I. 1.0-1.5), and for indeterminate colitis 11.7 per
      1000 person-years; (SMR 2.7, 95% C.I. 1.6-4.4). Complications of colitis were the
      main cause of death in both groups. The cancer risk was related to extent of
      disease, duration of disease and female gender. Ten out of the 12 cases with
      cancer had or developed total colitis. However, only seven of the 134 cases with
      total ulcerative colitis and two of 87 cases with total indeterminate colitis
      developed cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7636373
TI  - Anastomotic configuration does not affect recurrence of Crohn's disease after
      ileocolonic resection.
AB  - The influence of anastomotic configuration on recurrence of symptomatic Crohn's
      disease has been assessed in a sequential study of patients undergoing resection
      of ileal Crohn's disease. Between 1972 and 1991 92 patients had 102 ileocolonic
      anastomoses constructed after resection of intestinal Crohn's disease. The
      configuration of the ileocolonic anastomosis was either end to side (ES, n = 68)
      or side to side (SS, n = 34). The majority of patients in both groups were female
      and both groups were similar for duration of Crohn's disease at resection,
      steroid therapy, previous number of intestinal resections, indication for surgery
      and length of ileum resected at operation. No anastomotic leak occurred in either
      group. A total of 39 patients developed symptomatic recurrent Crohn's disease
      including 31 (46%) in the ES group and 8 (24%) in the SS group. This difference
      was related to the length of follow-up, the annual rate of symptomatic recurrence
      was almost identical for both end to side (0.066) and side to side (0.052)
      anastomoses.

PMID- 7636374
TI  - Two cases of colo-ovarian cyst fistula.
AB  - Fistula between the large bowel and an ovarian cyst is a recognised but rare
      pathological entity. We present two cases of colo-ovarian cyst fistula, the first
      occurring as a result of diverticular disease of the sigmoid colon and the second
      complicating a cystadenocarcinoma of the ovary. The aetiology of colo-ovarian
      cyst fistula is reviewed and the differential diagnosis is discussed.

PMID- 7636375
TI  - Transanal local excision of rectal cancer.
AB  - Twenty-five patients with invasive rectal cancer treated by transanal excision
      between 1978-1989 are presented. Two patients had poorly differentiated tumours
      and were converted to abdominoperineal resection and one patient had extensive
      liver metastases documented preoperatively. The remaining twenty-two, mean age 64
      years, fulfilled the criteria for local treatment. Eighty-two percent of tumours
      were T1 or T2 stage. There was no operative mortality. Six complications in five
      patients occurred, none requiring surgical intervention. Five patients died of
      unrelated causes without evidence of recurrence at 4, 4, 14, 26 and 58 months.
      The length of follow-up for the surviving group (17 patients) was 16 to 115
      months (mean 63 months). Two patients developed local recurrence at 32 and 60
      months. Transanal excision can be curative for selected rectal cancers.

PMID- 7636376
TI  - Non surgical management of colonoscopic bowel perforation.
AB  - Five patients (four males, and one female, median age of 60 years) with
      colonoscopy-related bowel perforations were managed between January 1993 and June
      1994. One patient had a difficult colonoscopy whereas four patients had
      polypectomies or biopsies. Abdominal pain was the main presenting symptom at a
      median of 3 h (range 2 to 12 h) following colonoscopy. Four patients demonstrated
      free pneumoperitoneum whilst one showed a pelvic abscess. Following non-surgical
      management, abdominal signs diminished after 24 to 48 h and disappeared by the
      fifth day in all patients. All patients were discharged well at day seven (range
      5 to 9 days) and have remained well at 12 months of follow-up (range 3 to 18
      months).

PMID- 7636377
TI  - Endosonography of the anal sphincters in solitary rectal ulcer syndrome.
AB  - Twenty-one patients with histologically proven solitary rectal ulcer syndrome
      (SRUS) were examined by anal endosonography (AES) in order to determine the
      frequency of any ultrasound abnormality. Comparison was made with a group of 17
      age and sex matched asymptomatic subjects. Four patients with SRUS had anal
      sphincter defects on AES. All were of the internal anal sphincter (IAS), which
      appeared fragmented in two patients with complete rectal prolapse. Measurements
      of internal and external anal sphincter (EAS) diameter and cross-sectional area
      were taken, excluding the 4 patients with defects. The submucosa was
      inhomogeneous (P = 0.0016) and thickness increased in patients with SRUS (median
      4.0 mm vs 2.0 mm; P < 0.0001). IAS diameter was increased (median 3.8 mm vs 2.0
      mm; P < 0.0001), as was cross-sectional area (median 241 sq mm vs 112 sq mm; P <
      0.0001). EAS diameter was also increased (median 8.5 mm vs 7.0 mm; P = 0.0173),
      as was cross-sectional area (median 905 sq mm vs 594 sq mm; P = 0.0052). The
      ratio of EAS to IAS thickness was reduced in patients with SRUS (median 2.6 vs
      4.0; P = 0.0029). The mechanism of these changes is unclear but apparent muscle
      hypertrophy on ultrasound may diagnose those patients with SRUS in whom
      defecatory difficulty is a predominant symptom.

PMID- 7636378
TI  - Intestinal endometriosis: presentation, investigation, and surgical management.
AB  - The study was undertaken to identify the presenting features of intestinal
      endometriosis and to evaluate its investigation and surgical management. Twenty
      six cases of intestinal endometriosis were identified during a fourteen year
      period. The commonest site of occurrence was the rectosigmoid region (11 cases)
      followed by the appendix (9 cases), and ileocaecal region (6 cases). Abdominal
      pain was the main presenting feature in 20 cases, with associated nausea and
      vomiting in 12 cases and altered bowel habit in ten. Other presenting features
      included rectal bleeding, abdominal bloating and tenesmus. Endometriosis was not
      suspected preoperatively in any of the patients without a past history of this
      condition. Accurate preoperative diagnosis proved very difficult, with only
      laparoscopy providing definite evidence of intestinal endometriosis prior to
      formal surgery. Colonic resections were performed in 12 cases, small bowel
      resection in six cases and appendicectomy in nine cases, together with resection
      of adjacent adherent structures. This series illustrates the difficulty of
      establishing an accurate preoperative diagnosis, and the propensity of intestinal
      endometriosis to mimic other gastrointestinal diseases, particularly carcinoma
      and inflammatory bowel disease.

PMID- 7636379
TI  - Solitary rectal ulcer and complete rectal prolapse: one condition or two?
AB  - We studied the physiological features of patients with complete rectal prolapse
      and different degrees of solitary rectal ulcer syndrome to determine whether
      these conditions are likely to form part of the same disorder. 52 solitary rectal
      ulcer patients (median age 31, 40 females), and 15 complete rectal prolapse
      patients (median age 31, 12 females) were studied. Solitary rectal ulcer patients
      were divided into 3 groups, based on the extent of accompanying rectal prolapse
      (no prolapse, internal prolapse, or external prolapse). Both solitary rectal
      ulcer patients without prolapse and with internal prolapse had significantly
      higher maximum anal resting (p < 0.01 for both groups) and squeeze pressure (p <
      0.05 for both groups) than complete rectal prolapse patients. In contrast,
      solitary rectal ulcer patients having external prolapse were similar to those
      with complete rectal prolapse. Solitary rectal ulcer patients without rectal
      prolapse had significantly decreased anal and rectal electrosensitivity (p < 0.01
      for both) when compared to healthy control subjects. Solitary rectal ulcer
      patients therefore have a spectrum of clinical and physiological features--this
      condition may comprise a range of different disease entities. The findings also
      suggest a different underlying aetiopathophysiology of solitary rectal ulcer from
      that of complete rectal prolapse.

PMID- 7636380
TI  - Scintigraphic assessment of colonic function during defaecation.
AB  - The aim of this study was to develop a method by which rectal and colonic
      activity could be examined during defaecation under physiological conditions, in
      order to evaluate whether the colon plays a role in defaecation. Subjects
      presented to the Nuclear Medicine department on the day following ingestion of
      oral In-111 labelled DTPA, when they developed the normal urge to defaecate.
      Defaecation took place in a private room while dynamic scintigraphy of the rectum
      and colon was recorded. Fourteen subjects were studied (8 normal subjects, 4 with
      constipation, 2 with irritable bowel syndrome). In 13 subjects the left colon was
      visualized during defaecation and emptying was clearly observed in 12. The right
      colon was visualised in 11 subjects and emptying was seen in 7. Mean percentage
      segmental evacuation was right colon 20%, left colon 32% and rectum 66%. Colonic
      emptying occurs during defaecation, which is not a process of rectal evacuation
      only. This has implications for the understanding of the pathophysiology of
      obstructed defaecation.

PMID- 7636381
TI  - Fistula in ano: a surgical audit.
AB  - OBJECTIVE: To document a 15 year experience of fistula in ano surgery. DESIGN:
      Retrospective audit of patients. SUBJECTS: All patients referred with fistula in
      ano between 1975 and 1990. SETTING: Colorectal Service, University Department of
      Surgery, Wellington School of Medicine. MAIN OUTCOME MEASURES: Resolution of
      symptoms and morbidity of surgery. RESULTS: 92 operations were performed in 88
      patients. There were 65 males (39.6 year) and 23 females (25.9 year). Two
      patients were operated on two occasions and one patient with Crohn's disease (CD)
      had three fistulae laid open over a two year period. Three further patients with
      CD had one operation each. One patient had mucosal ulcerative colitis, one
      patient was found to have a carcinoma in situ close to the fistula tract and one
      had a carcinoma in the fistulous tract. There were no postoperative deaths. Over
      50% of the patients were discharged within three days of surgery. No patient
      complained of anal incontinence at the time of discharge. Two patients returned
      with recurrence (a cryptogenic sepsis recurrence rate of 2.3%). CONCLUSION: Low
      fistulae in ano can be very satisfactorily managed by simple laying open. The
      recurrence rate following surgery is low, and there have been no complaints of
      problems with continence.

PMID- 7636382
TI  - Does surgery resolve outlet obstruction from rectocele?
AB  - In order to ascertain whether plastic surgery for rectocele is of value in the
      treatment of outlet obstruction, a retrospective study was made of 21 women
      complaining of difficulty in expelling faeces: 13 patients (group A) underwent
      surgery with transanal longitudinal plication of the anterior rectal wall
      (Block's technique), and 8 patients (group B) had colpoperineoplasty which, in 2,
      was associated with bladder-neck suspension following the Raz-Peyrera technique
      for urinary incontinence. The mean follow-up was 24.2 +/- 18.7 and 36.8 +/- 17.8
      months respectively. In 11 group A patients (80.9%) and 6 group B patients (75%)
      cure, or an improvement, was achieved. Of the remaining 4 patients (19%),
      recurrent rectocele was found in 2 (one group A and one group B) and intestinal
      transit time tests detected colonic constipation in one group A and in one group
      B patient. It is concluded that surgery can resolve outlet obstruction from
      rectocele, but Block's technique is preferable because it is more straight
      forward and easier.

PMID- 7636383
TI  - Metallothionein and the acute phase response.

PMID- 7636384
TI  - Participation of pulmonary alveolar epithelial cells in lung inflammation.
AB  - As our understanding of pulmonary inflammation improves, the complexity of the
      mechanisms involved becomes more and more apparent. The number of soluble
      inflammatory mediators that are being recognized and characterized is increasing
      rapidly. The major purpose of this review is to emphasize that developing a
      comprehensive understanding of pulmonary inflammation requires investigations
      that encompass all of the cellular components. More than just a stage on which
      inflammatory processes are played out, the alveolar epithelium can participate in
      virtually all aspects of inflammation, including initiation, amplification, down
      regulation, and tissue repair. By directing the powerful tools of cellular and
      molecular biology to study the entire cast of cellular players, a more complete
      understanding of inflammation will surely result. Such a comprehensive approach
      should assist in the development of means to prevent and treat inflammatory lung
      diseases.

PMID- 7636385
TI  - Dissociation between tissue iron concentrations and transferrin saturation among
      inbred mouse strains.
AB  - Excessive absorption of dietary iron results in pathologic hepatic iron
      accumulation in the genetic disorder hemochromatosis. Genetic factors have also
      been suggested to play a role in African iron overload that is induced by the
      intake of iron-rich fermented beer. We have used inbred strains of mice to
      investigate previously unrecognized genetic factors controlling iron metabolism.
      Among different strains of mice fed a basal iron diet, serum iron levels varied
      twofold. In contrast, serum transferrin levels were remarkably constant. This
      indicates that transferrin saturation with iron, but not the serum level of
      transferrin, is likely to be genetically determined in mice. Hepatic iron stores
      also varied twofold among the different mouse strains. Remarkably, hepatic iron
      stores failed to reflect transferrin saturation, suggesting that different
      genetic factors control transferrin saturation and hepatic iron stores. When mice
      were challenged with a high-iron diet, the concentration of carbonyl iron
      required to completely saturate transferrin with iron was 10 times greater for
      C57BL/6 and BALB/c mice than for DBA/2 and AKR mice. These results are
      reminiscent of the iron-loading locus proposed to interact with dietary iron in
      African iron overload. Our studies with inbred strains of mice have revealed a
      number of novel control points in iron metabolism that may be genetically
      determined. The mouse model may thus be useful for understanding the molecular
      basis of hemochromatosis and African iron overload.

PMID- 7636386
TI  - Myositis and fasciitis associated with group A beta hemolytic streptococcal
      infections: development of a rabbit model.
AB  - Group A streptococci produce a variety of clinical symptoms ranging from minor
      pharyngeal infections to life-threatening soft-tissue disease. A rabbit model is
      described for induction of myonecrosis and fasciitis with group A beta-hemolytic
      streptococci. Group A streptococcal infections have shown remarkable virulence in
      recent years, resulting in severe local tissue destruction and life-threatening
      toxicity. After subcutaneous injection into the thigh of 20 ml broth containing
      10(5) to 10(9) cfu/ml, initial soft tissue infection rapidly progressed to
      rhabdomyolysis. The response of the rabbits to the infection was consistent with
      the human response.

PMID- 7636387
TI  - Correlation of low histidine rich glycoprotein plasma levels with the occurrence
      of acute graft-versus-host disease after allogeneic bone marrow transplantation.
AB  - Histidine-rich glycoprotein (HRGP) is a potent inhibitor of T cell activation and
      production of cytokines such as (gamma-IFN). gamma-IFN released by activated T
      cells is increased during a short-term period at the onset of GvHD after
      allogeneic bone marrow transplantation. Therefore we investigated HRGP plasma
      levels in patients after BMT. Blood was collected from 20 children before and up
      to 6 weeks after BMT. In patients without GvHD, HRGP plasma levels decreased
      during the first week after BMT to 237 +/- 60 micrograms/ml, compared with 302 +/
      104 micrograms/ml before transplantation. However, no significant changes in
      mean HRGP plasma levels were observed during the following 5 weeks of the
      posttransplantation period. Acute GvHD occurred in 10 of 20 patients between the
      second and third week after BMT. HRGP levels (mean +/- SEM) in patients with GvHD
      dropped during the first week to 158 +/- 32 micrograms/ml, compared with
      pretransplant levels of 240 +/- 48 micrograms/ml). In contrast to results in
      patients without GvHD, a second and significant decrease was obtained between the
      second and third week after BMT in patients with GvHD (161 +/- 35 micrograms/ml
      vs 84 +/- 13 micrograms/ml; p < 0.01). In the third week after BMT, HRGP levels
      were significantly lower in patients with GvHD as compared with patients without
      GvHD (166 +/- 29 micrograms/ml; p < 0.01). The decrease in HRGP in the second and
      third posttransplantation week was not a result of steroid treatment.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7636388
TI  - The effect of cell-free hemoglobin on intravascular clearance and cellular,
      plasma, and organ distribution of bacterial endotoxin in rabbits.
AB  - Cell-free hemoglobin (Hb) and bacterial endotoxin (LPS) synergistically produce
      toxicity. To elucidate possible mechanisms, three groups of rabbits received LPS
      alone, LPS plus human serum albumin (HSA), or LPS plus Hb (Hb group). The
      intravascular retention of injected iodine 125-labeled LPS during the 30-minute
      period analyzed was significantly longer in the Hb group than in the LPS alone or
      HSA groups (p = 0.0007 and p = 0.03, respectively), especially during the initial
      10 minutes. The intravascular half-life of LPS in the LPS control, HSA, and Hb
      groups was 2.8, 4.0, and 4.9 minutes, respectively; the area under the curve was
      1369 +/- 483, 1594 +/- 360, and 1731 +/- 481, respectively (ng/ml x minutes, mean
      +/- SD); and the total body clearance was 24.7 +/- 9.2, 20.1 +/- 5.4, and 18.9 +/
      6.0 (ml/min, mean +/- SD), respectively. The proportion of LPS associated with
      blood cells was very small at the initial 1-minute time period, and this
      decreased even further during the 30-minute period analyzed (p = 0.0001). Over
      96% of injected LPS was associated with the cell-free plasma, with 51% to 54% of
      LPS in the apoprotein fraction at the initial time point and 35% to 37% in the
      HDL fraction. The proportion of LPS increased significantly in the HDL fraction
      and decreased significantly in apoproteins during the 30-minute period analyzed
      (p = 0.0006 and p = 0.002, respectively). However, there were no differences
      between the three groups. The liver was the main distribution site (74%) of
      injected LPS among the six organs evaluated. In the Hb group the accumulation of
      125I-labeled LPS in the spleen was significantly lower than that in the HSA group
      (p = 0.05). The synergism of the in vivo toxicity reported for LPS and Hb may be
      due, in part, to the decreased rate of intravascular clearance of endotoxin.

PMID- 7636389
TI  - Comparison of latex antigens from surgical gloves, ammoniated and nonammoniated
      latex: effect of ammonia treatment on natural rubber latex proteins.
AB  - Immediate hypersensitivity to latex proteins from contact with natural rubber
      latex gloves has been increasingly reported, especially in health care workers.
      Proteins in the latex responsible for these reactions may potentially be
      extractable, adsorbed on glove powder, or remain unextractable. Because these
      gloves are manufactured from ammoniated natural rubber latex, our knowledge on
      the effect of ammonia on latex proteins is incomplete. Therefore, we have
      investigated the effect of ammoniation on the protein profile and antigenicity or
      allergenicity of natural rubber latex proteins (NAL). Results indicate that
      ammonia treatment leads to breakdown and even precipitation of certain latex
      proteins. However, the antigenicity or allergenicity of NAL is preserved in the
      degraded proteins that present as extractable latex antigens of gloves. In
      addition to the proteins present in glove extract and proteins adsorbed to glove
      powder, certain latex proteins (23, 10, and 8 kd) remain firmly bound to glove
      film as "unextractable" latex antigens that cannot be removed by washing. The
      unextractable latex antigens may represent the antigens precipitated by ammonia
      treatment and may be associated with latex allergy.

PMID- 7636390
TI  - Pulmonary immune response of young and aged mice after influenza challenge.
AB  - After influenza challenge, aged mice have prolonged viral shedding that
      correlates with lower splenic cytotoxic T lymphocyte (CTL) activity. To evaluate
      the age-related pulmonary cell-mediated immune response to influenza, pulmonary
      lymphocytes were obtained from young and aged mice at various days after
      respiratory tract infection with nonlethal influenza A/PC/1/73 (H3N2) virus. In
      young mice, pulmonary CTL activity peaked at 48% +/- 2% on day 7 after infection.
      Pulmonary CTL activity peaked 1 day later in aged mice and at about half the
      activity (24% +/- 5%). The majority of the cells recovered from the lungs in both
      age groups were CD3+, CD8+ T cells. Histologic examination of the lungs revealed
      that aged mice had significantly less inflammation than young mice. Therefore,
      after influenza challenge there was a large influx of lymphocytes into the lungs
      of both young and aged mice, but the cells from young mice were more active on a
      per-cell basis. In a further experiment, challenge with a more virulent strain of
      influenza produced higher mortality in young mice than in aged mice. Thus the
      higher CTL activity of young animals leads to more rapid virai clearance, but
      this may be at a price to the host--that is, more immunopathologic damage.

PMID- 7636391
TI  - The expression of acetyl coenzyme A carboxylase is related to megakaryocyte
      maturation.
AB  - We have previously demonstrated that de novo fatty acid synthesis predominantly
      occurs in later phases of megakaryocyte maturation. Therefore we have
      investigated the expression of fatty acid synthase (FAS) and acetyl coenzyme A
      carboxylase (ACC), key enzymes for fatty acid synthesis in megakaryocytes at
      different phases of maturation. Immature and mature megakaryocytes were isolated.
      Guinea pig-specific FAS and ACC cDNA probes were prepared by reverse
      transcriptase reaction-polymerase chain reaction (RT-PCR). The probes were used
      to assess the expression of mRNA for ACC and FAS by Northern blotting. The
      hybrids were quantitated by densitometry. Endogenous megakaryocyte ACC was
      quantitated by virtue of its biotin content by Western blotting with streptavidin
      and enhanced chemiluminescence (ECL). The ratio of ACC mRNA between mature and
      immature megakaryocytes was 2.43 +/- 0.86, and the ratio of FAS mRNA was 0.50 +/-
      0.13 (mean +/- SD, n = 4). The ratio of endogenous ACC in mature and immature
      megakaryocytes was 1.96 +/- 0.62 (n = 6). The study showed that the FAS mRNA was
      expressed in all phases of megakaryocyte maturation. However, both mRNA for ACC
      and endogenous ACC were demonstrated primarily in mature megakaryocytes. Thus de
      novo fatty acid synthesis in megakaryocytes may depend on the expression of ACC
      in mature cells. The expression of ACC occurs during the terminal phases of
      megakaryocyte maturation and may be a marker of megakaryocyte maturity.

PMID- 7636392
TI  - Maternal-to-fetal transfer of 5-methyltetrahydrofolate by the perfused human
      placental cotyledon: evidence for a concentrative role by placental folate
      receptors in fetal folate delivery.
AB  - Folates play a vital role in cellular processes that are essential for fetal
      growth and viability. Thus the human placenta, which contains high-affinity
      membrane-associated placental folate receptors (PFRs), maintains a concentrative
      maternal-to-fetal flux of the vitamin under conditions of minimal dependence on
      variations of maternal dietary intake. To define transplacental folate transport
      and the role of PFRs in this mechanism, we utilized the isolated perfused human
      placental cotyledon. In closed system perfusions with 10 nmol/L 5
      methyltetrahydrofolate, placental binding was rapid and extensive (47%), with a
      gradual maternal-to-fetal transfer of 5-methyltetrahydrofolate. Although
      hydrophilic PFRs were released into the fetal perfusate, PFR-bound folates
      constituted only a fraction of net transplacental folate transport. Transfer was
      bidirectional, not saturable, not inhibited by anion channel blockers, and
      dependent on perfusate levels. Placental binding far exceeded transfer, and
      pulsing the maternal circuit with tritiated 5-methyltetrahydrofolate, followed by
      washout of unbound radiolabel and rechallenge with unlabeled 5
      methyltetrahydrofolate or folate, led to release of bound tritiated 5
      methyltetrahydrofolate, illustrating reversible binding. Perfusion with the N
      hydroxysuccinimide ester of folic acid eliminated essentially all 5
      methyltetrahydrofolate binding to PFRs, while increasing net maternal-to-fetal
      transfer of the vitamin. Finally, because it has been suggested that impaired
      placental transport of folate may be linked to the fetotoxic effects of ethanol,
      the effect of this compound on the above processes was examined. An acute 6-hour
      exposure to ethanol (2.5 to 3.1 mg/ml) had no effect (p > 0.05) on net maternal
      to-fetal transfer of 5-methyltetrahydrofolate. These studies suggest that net
      maternal-to-fetal transfer is a process consisting of two steps. First is the
      concentrative component in which circulating 5-methyltetrahydrofolate is bound to
      (captured by) PFRs on the maternally facing chorionic surface. Although kinetics
      favor binding, there is a dynamic state wherein a gradual release of 5
      methyltetrahydrofolate from this pool can add to incoming circulating folates to
      generate an intervillous blood level approximately 3 times that in the maternal
      blood. In the second step, folates are passively transferred to the fetal
      circulation along a downhill concentration gradient. This unique mechanism for
      transplacental folate transport may be applicable to other small relative
      molecular mass ligand nutrients that bind to high-affinity placental receptors.

PMID- 7636393
TI  - Effects of intraperitoneal cyclooxygenase inhibition on inflammatory mediators in
      dialysate and peritoneal membrane characteristics during peritonitis in
      continuous ambulatory peritoneal dialysis.
AB  - Peritonitis complicating continuous ambulatory peritoneal dialysis (CAPD) can be
      used as an in vivo model to study the contribution of mediators in dialysate to
      the regulation of peritoneal permeability. Previously we reported that changes in
      the peritoneal appearance rates of the cytokines interleukin-6 (IL-6) and tumor
      necrosis factor-alpha (TNF alpha) were related to alterations in the effective
      peritoneal surface area. Changes in the intrinsic peritoneal permeability were
      mainly related to those in the peritoneal appearance rate of the prostanoid
      prostaglandin E2 (PGE2) and partly also to that of IL-6. In this intervention
      study the role of these mediators was further analyzed. Eleven peritonitis
      episodes were followed on 8 consecutive days from the start of the infection and
      once after recovery. Indomethacin was given intraperitoneally during the first 3
      days. beta 2-Microglobulin clearance was used as indicator of the effective
      peritoneal surface area. The intrinsic peritoneal permeability was characterized
      functionally by the restriction coefficient. The 15 peritonitis episodes studied
      previously served as the control group. This study supports the formerly obtained
      relationships in two ways. First, significant reductions were observed for
      peritoneal PGE2, 6-keto-PGF1 alpha, and TxB2 during cyclooxygenase inhibition to
      6%, 0.6%, and 9% of the values on day 1, whereas simultaneously the intrinsic
      permeability was less increased. This indomethacin effect on intrinsic
      permeability was not entirely significant, probably because of the additional
      role of IL-6, which was not influenced by indomethacin. Also, the appearance rate
      of TNF alpha in the effluent was not affected by cyclooxygenase inhibition.
      Accordingly, the changes in the effective surface area were similar to those in
      the control group. Second, in 8 of the 11 cases, new rises both in peritoneal
      PGE2 and in intrinsic permeability occurred after discontinuation of
      indomethacin. Rebounds were not seen for TNF alpha or IL-6, and, consistently,
      not for the effective surface area. In conclusion, local cyclooxygenase
      inhibition results in a less-increased intrinsic permeability during peritonitis
      but has no effect on the effective surface area. These data support our previous
      finding that IL-6 and TNF alpha contribute to alterations in surface area,
      whereas PGE2 is more involved in intrinsic peritoneal permeability changes.

PMID- 7636396
TI  - Epidemiology of sudden infant death syndrome (SIDS) for Kentucky infants born in
      1990: maternal, prenatal, and perinatal risk factors.
AB  - Using state vital statistics data for infants born to Kentucky residents in 1990,
      a nonconcurrent prospective study design was used to evaluate various risk
      factors for infant mortality from Sudden Infant Death Syndrome (SIDS). For
      comparison, an identical analysis was performed for infant mortality from all
      causes combined, including SIDS. The following factors were considered as
      potential risks: infant low birthweight, maternal age at delivery, maternal
      education, maternal cigarette and alcohol use during pregnancy, prenatal care,
      maternal race, method of delivery, premature birth, sex of the child, and
      multiple (twin or more) birth. A categorical analysis was used to calculate an
      adjusted relative risk for each potentially significant (p < 0.10) risk factor.
      Potentially significant adjusted relative risks for SIDS are maternal age under
      20 (1.73, p < or = 0.08), maternal years of education (0.80 for one year, p <
      0.01), maternal cigarette use (1.92 for one pack per day, p < 0.01), Cesarean
      delivery (2.09, p < or = 0.01), and premature birth (1.76, p < or = 0.08).
      Potentially significant adjusted relative risks for infant death from all causes
      are low birthweight (5.93, p < 0.01), maternal age over 35 (1.54, p < or = 0.05),
      maternal years of education (0.94 for one year, p < or = 0.02), marginal prenatal
      care (1.47, p < or = 0.01), premature birth (1.47, p < 0.01), and female sex
      (0.82, p < or = 0.05). Given this data, there may be unique risk factors for
      SIDS. The implications of these findings are discussed.

PMID- 7636394
TI  - Cyclic adenosine monophosphate and protein kinase C modulate fibronectin
      production in cultured human mesangial cells.
AB  - To identify potential intracellular mediators of mesangial cell fibronectin
      production, we examined the effect of cyclic adenosine monophosphate and protein
      kinase C on fibronectin biosynthesis in cultured human mesangial cells. We found
      that increasing intracellular cyclic adenosine monophosphate resulted in a 2.6
      fold increase in fibronectin mRNA expression within 15 minutes; this reached a
      plateau after 1 hour and fell below control levels by 24 hours. Cyclic adenosine
      monophosphate significantly increased both immunoreactive fibronectin levels and
      the incorporation of [35S]-labeled methionine into fibronectin after 1 and 2
      hours (251% +/- 3% and 157% +/- 18% of controls, respectively). The induction of
      protein kinase C with phorbol ester also increased fibronectin mRNA expression.
      The effect was time and dose dependent. Phorbol ester significantly increased
      both immunoreactive fibronectin levels and the incorporation of [35S]-labeled
      methionine after 1 and 2 hours (174% +/- 2% and 224% +/- 6% of controls,
      respectively). Inhibition of protein kinase C with calphostin C attenuated
      constitutive and phorbol ester induced fibronectin biosynthesis. These studies
      indicate that cyclic adenosine monophosphate and protein kinase C regulate
      mesangial cell fibronectin biosynthesis and that protein kinase C may contribute
      to control of constitutive fibronectin production.

PMID- 7636395
TI  - Medical stewardship.

PMID- 7636397
TI  - Benign schwannoma of the small intestine: an unusual cause of gastrointestinal
      bleeding.
AB  - Neurogenic tumors of the small intestine are exceedingly rare accounting for less
      than 1% of all neoplasms involving the gastrointestinal (GI) tract. These lesions
      may remain clinically silent for years, but usually manifest by the 5th or 6th
      decade of life. Occult transient hemorrhage from the GI tract interspersed by
      relatively long asymptomatic periods is the most common presentation. This report
      describes a case of a patient with a solitary benign duodenal schwannoma and no
      prior symptoms presenting as an acute life-threatening upper GI hemorrhage. Small
      bowel tumors of neurogenic origin represent an unusual cause of GI hemorrhage.
      The diagnosis should be considered in such cases to insure appropriate and timely
      management.

PMID- 7636398
TI  - Bilateral ectopic pregnancy. A case report.
AB  - Bilateral ectopic pregnancy is a rare phenomenon. It has been 76 years since the
      first published report of a case of bilateral ectopic pregnancy. Since then about
      200 cases have been reported in the literature; we report a case here.

PMID- 7636399
TI  - Release of patient medical records.

PMID- 7636400
TI  - Physician, heal thyself.

PMID- 7636401
TI  - International symposium on critically ill newborns. An overview and introduction.

PMID- 7636402
TI  - Critically ill newborns and the law. The American experience.

PMID- 7636403
TI  - Treatment of critically ill newborns in Australia.

PMID- 7636404
TI  - Beyond the threshold of life. Treating and non-treating of critically ill
      newborns in The Netherlands.

PMID- 7636405
TI  - Care of critically ill newborns. The Israeli experience.

PMID- 7636406
TI  - Care of critically ill newborns in India. Legal and ethical issues.

PMID- 7636407
TI  - Collective bargaining for nurses under the National Labor Relations Act. A look
      at the future.

PMID- 7636408
TI  - Comparison of 1.5 Tesla and 0.35 Tesla field strength magnetic resonance imaging
      scans in the morphometric evaluation of the lumbar intervertebral foramina.
AB  - OBJECTIVE: To compare magnetic resonance imaging (MRI) scans obtained from 1.5
      Tesla (T) MRI units with scans obtained from 0.35T MRI units in the morphometric
      evaluation of the lumbar intervertebral foramina (IVF). DESIGN: Three dimensions
      of lumbar IVFs were measured on a cadaveric lumbar spine by using Vernier
      calipers. The spine was embedded in gelatin to simulate soft tissue and scanned
      twice in a 1.5T MRI unit (3-mm and 5-mm slice thicknesses) and once in a 0.35T
      MRI unit (5-mm slice thickness). Measurements from the scans were made
      independently by three observers. The results obtained from the two units were
      compared to the actual IVF size (as measured by calipers) and to one another.
      RESULTS: The greatest superior-to-inferior distance had the strongest
      statistically significant correlation to the actual cadaver measurements for both
      the 0.35T and 1.5T imaging units [r = 0.986 (0.35T); r = 0.985 (1.5T at 3 mm) and
      r = 0.981 (1.5T at 5 mm); p < .0001 in all cases]. Mean differences and standard
      errors were minimal between measurements made from MRI scans of both 1.5T and
      0.35T units and measurements made directly from the cadaveric spine. CONCLUSION:
      Both imaging units produced images that accurately depicted the actual size of
      the IVF. The MRI units of 0.35T field strength produced images of high
      morphometric accuracy. In addition, the potential for side effects and the
      operating costs are less with 0.35T units. Therefore, 0.35T MRI units may be a
      prudent choice as a clinical and research imaging tool in the evaluation of the
      lumbar IVF.

PMID- 7636409
TI  - Misuse of the literature by medical authors in discussing spinal manipulative
      therapy injury.
AB  - OBJECTIVE: This study was conducted to determine how the words chiropractic and
      chiropractor have been used in publications in relation to the reporting of
      complications from cervical spinal manipulation therapy (SMT). STUDY DESIGN: The
      study method was to collect recent publications relating to spinal manipulation
      iatrogenesis which mentioned the words chiropractic and/or chiropractor and then
      determine the actual professional training of the practitioner involved. METHOD:
      The training of the practitioner in each report was determined by one of three
      means: surveying previous publications, surveying subsequent publications and/or
      by writing to the author(s) of ten recent publications which had used the words
      chiropractic and/or chiropractor. RESULTS: This study reveals that the words
      chiropractic and chiropractor commonly appear in the literature to describe SMT,
      or practitioner of SMT, in association with iatrogenic complications, regardless
      of the presence or absence of professional training of the practitioner involved.
      CONCLUSION: The words chiropractic and chiropractor have been incorrectly used in
      numerous publications dealing with SMT injury by medical authors, respected
      medical journals and medical organizations. In many cases, this is not
      accidental; the authors had access to original reports that identified the
      practitioner involved as a nonchiropractor. The true incidence of such reporting
      cannot be determined. Such reporting adversely affects the reader's opinion of
      chiropractic and chiropractors.

PMID- 7636411
TI  - A comparative study of two methods for obtaining the anteroposterior open mouth
      cervical view.
AB  - OBJECTIVE: To compare two methods of obtaining the anteroposterior (AP) open
      mouth view. DESIGN: Radiological evaluation of the occiput-C1/C1-C2 structures,
      as visualized on radiographs obtained using two different radiographic position
      set-ups. SETTING: The Anglo-European College of Chiropractic Clinic. PATIENTS: A
      total of 60 patients. Each method used on 30 patients. CRITERIA ASSESSED:
      Visualization of: (a) occiput-C1 joints, (b) atlantoaxial joints, (c) lateral
      masses C1 and (d) odontoid process. RESULTS: The visualization of the occiput-C1
      joints was increased almost 100% using method 2. The atlantoaxial joints were
      seen in 7% more cases using method 2 and the lateral masses were seen in 10% more
      cases. The only structure seen more consistently using method 1 was the odontoid
      process, which was seen in 7% more cases using that method. CONCLUSION: This
      study shows that there is an easier and more consistent method of obtaining the
      AP open mouth view than that traditionally used in many institutions.

PMID- 7636410
TI  - Smokers exhibit an altered Doppler analog waveform during peripheral arterial
      examination.
AB  - OBJECTIVE: To identify an analog waveform characteristic of smokers by Doppler
      sonography, which reflects their atherogenic state, and to determine if the
      presence of this aberrant waveform will increase the sensitivity of the ankle
      pressure index (API) peripheral Doppler examination. Also, to examine the
      relationship between pac-yr smoked and arterial compliance. DESIGN: A cross
      sectional design was used to examine the diastolic component of the triphasic
      arterial analog waveform. A comparison between the Doppler studies of smokers and
      nonsmokers was constructed. SETTING: A university-based study from the Department
      of Applied Physiology, Teachers College, Columbia University. PARTICIPANTS:
      Studied were a total of 140 sedentary subjects consisting of 70 controls and 70
      smokers. Control subjects were sedentary and never smoked. Each group consisted
      of an equal number of male and female subjects. Smoking subjects had smoked 37.8
      +/- 21.4 mean pac-yr and were sedentary. No subject had hypertension, diabetes,
      hyperlipidemia or cardiac disease. They had no evidence of myocardial infarction,
      arrhythmia, aortic coarctation, cardiac valve disease or peripheral arterial
      disease. Anthropometric measurements and percent body fat were recorded. A
      predictive, oxygen-consumption, bike ergometer test was performed to determine
      aerobic capacity. The standard API Doppler examination and arterial diastolic
      flow analysis were performed with A-mode Doppler ultrasound on all subjects. MAIN
      OUTCOME MEASURE: The amplitude of the diastolic component of the triphasic
      arterial analog waveform was examined by diastolic flow analysis. This method has
      been shown to quantify arterial compliance, which is a correlate of
      arteriosclerotic disease. RESULTS: A statistically significant difference (p <
      .001) existed between the mean arterial compliance values of the control and
      smoking groups. The mean arterial compliance value for the control group was 21.3
      +/- 3.7% and 4.9 +/- 4.7% for the smoking group. The mean quantity of arterial
      compliance in the control group was 4.3 times greater than that observed in the
      smoking group. A significant inverse-linear relationship was observed between pac
      yr smoked and arterial compliance (p < .001). CONCLUSION: When utilizing Doppler
      to identify lower-extremity occlusive disease, these results demonstrate that
      smokers display a distinctive analog waveform. The morphology of the waveform is
      characterized by an attenuated diastolic component of the analog triphasic
      complex. This finding reflects an advanced state of arterial disease. In our
      study, this characteristic waveform was identified when API remained negative.
      When examining the results of a Doppler peripheral arterial study in a
      claudication patient, the identification of this waveform suggests that advanced
      atherogenic changes have occurred.

PMID- 7636412
TI  - Soft-tissue compliance measurements in the spinal region of children with
      juvenile chronic arthritis compared with healthy children and adults.
AB  - OBJECTIVE: Study 1. To compare paraspinal soft-tissue compliance in asymptomatic
      (healthy) adults with children and to define reference values in children. Study
      2. To determine whether the reference values in asymptomatic children differ from
      children with juvenile chronic arthritis (JCA). STUDY DESIGN: A tissue-pressure
      compliance meter (TPCM) was used in the paraspinal region of 69 asymptomatic
      children, 28 asymptomatic adults and in 57 children with JCA. The tissue
      compliance was assessed paraspinally at level C6, T1, T3, T6, T10, L3 and L5.
      MAIN FINDINGS: Study 1: Differences between asymptomatic children and adults were
      not significant, except for the thoracolumbar junction, i.e., area T10, L1 and
      L3. Asymptomatic men showed a greater amount of displacement at area C6; adult
      asymptomatic women at area L3 and L5. The cervical and lumbar areas were shown to
      have the greatest amount of displacement and the thoracic area the least. Study
      2. No significant differences were found between the compliance of the JCA group
      and the asymptomatic group, except for paraspinal area L3. CONCLUSION: Study 1.
      The curvature within the spinal region in adults and children may have influenced
      the amount of soft-tissue displacement; sexual maturation may have affected soft
      tissue displacement as well. Study 2. Paraspinal soft-tissue compliance exhibited
      no alterations in JCA that could be segmentally related to inflamed joints.

PMID- 7636413
TI  - Reflex responses associated with manipulative treatments on the thoracic spine: a
      pilot study.
AB  - OBJECTIVE: To test systematically if spinal manipulative treatments (SMT) and the
      audible release associated with SMT cause activation of spinal muscles. DESIGN:
      Experimental pilot study. SETTING: Human Performance Laboratory, The University
      of Calgary. PARTICIPANTS: One male and one female asymptomatic volunteer.
      INTERVENTION: Slow and fast SMTs to the left transverse process of thoracic
      vertebrae using a reinforced hypothenar contact. The treatment forces were
      directed in a posterior-to-anterior direction with the subjects in a prone
      position. MAIN OUTCOME MEASURES: Forces applied by the chiropractor during SMT.
      Measurements of the audible release using skin-mounted accelerometers.
      Electromyographical activity of selected spinal muscles. RESULTS:
      Electromyographical (EMG) activity was observed consistently 50-100 msec after
      the onset of each of the fast SMTs, whether the treatment resulted in an audible
      release or not; for slow SMTs, there was never any visible electromyographical
      activity of the target muscles, whether the treatment resulted in an audible
      release or not. CONCLUSION: The results of this study suggest that fast treatment
      thrusts elicit muscle activation, whereas slow force application does not. The
      timing of the onset of the EMG response suggests that activation may be produced
      by a reflex response originating in the muscle spindles. It also appears that the
      audible release does not (by itself) evoke muscle activation or a joint
      proprioceptive reflex response as has been speculated in the literature.

PMID- 7636414
TI  - Does smoking cause low back pain? A review of the epidemiologic literature for
      causality.
AB  - BACKGROUND: Smoking has been associated with low back pain (LBP) in several
      epidemiologic studies but the results are contradictory. Despite this, smoking is
      often assumed to be a causative factor of LBP. STUDY OBJECTIVE: To appraise the
      epidemiologic literature to establish whether there is evidence for a causal link
      between smoking and LBP. DATA SOURCES: Twenty-two original research reports
      published between 1974 and 1993 were reviewed and a systematic investigation was
      made of eight of these, which were retained because they included study samples
      representative of their target populations. DATA SYNTHESIS: To uncover any
      evidence for a causal relationship between smoking and LBP, these eight reports
      were examined in detail for strength of association, dose-response effect,
      temporality and consistency of findings. RESULTS: Some studies found a positive
      association between smoking and LBP; when present, the strength of this
      association was generally small. Some associations remained unchanged after
      multivariate analysis, whereas others became statistically nonsignificant.
      Contradictory results were also noted in studies which reported on the dose
      response relationship and time of exposure in relation to time of onset of LBP.
      There was inconsistency of findings within and between studies relating to LBP.
      However, the evidence was consistently against a causal association between
      smoking and sciatica/discal hernia. CONCLUSION: It cannot be clearly deduced
      whether smoking has a causal effect on LBP or whether the positive findings
      sometimes noted are linked to some other, still unidentified factor. However,
      there is clearly no proof supporting a causal association between smoking and
      sciatica/discal hernia.

PMID- 7636415
TI  - Cervical radiculopathy: a case for ancillary therapies?
AB  - OBJECTIVE: To present two cases, one of a patient with a radicular syndrome and
      another of a patient with a pseudoradicular syndrome. CLINICAL FEATURES: A 45-yr
      old man visited one chiropractic clinic complaining of a "pinched nerve" in his
      neck, with pain and paresthesia in his left hand. He reported that these symptoms
      began after a work accident 1 month before, when he lifted a heavy object.
      Radiographs revealed disk space thinning at C4-5, C5-6 and C6-7. CT scans
      revealed foraminal narrowing with a minor disk bulging at the level of C5-6 and a
      large disk protrusion at C7-T1. The second patient is a 60-yr-old man with left
      shoulder and cervical spine pain. The patient stated that the shoulder pain felt
      like an ache and had begun 2 wk earlier when he had awakened with pain in the
      shoulder and a stiff neck. X-ray evaluation revealed a moderate level of
      degenerative change at the the C4-5, C5-6 and C7-T1 region. CONCLUSION: This
      article identifies the similarities and variations between two syndromes
      receiving chiropractic intervention that included ancillary therapy. Certain
      conditions, including cervical radiculopathy, seem to respond well to
      chiropractic spinal manipulative therapy. However, in other conditions with
      similar symptomatology, appropriate referral may be necessary for the condition
      to respond. Alternatively, adjunctive or ancillary therapy may be indicated to
      improve the effect of the chiropractic intervention.

PMID- 7636416
TI  - Solitary osteochondroma of the cervical spine.
AB  - OBJECTIVE: To discuss a case of cervical spine osteochondroma found incidentally
      during evaluation of a rib injury. To demonstrate diagnostic imaging, including
      plain film radiography, radionuclide bone scan, computed tomography and magnetic
      resonance imaging. CLINICAL FEATURES: This article presents the second reported
      case of osteochondroma associated with the C6 vertebral body. The classic imaging
      features of exostosis and a cartilaginous cap were identified. The osteochondroma
      was confluent with marrow of the C6 articular pillar. A biopsy was performed for
      confirmation of the lesion's histological character. INTERVENTION: Surgical
      resection was performed to remove the osteochondroma. CONCLUSION: Clinical
      examination, radiological evaluation and advanced diagnostic imaging helped
      detect and characterize an incidental cervical spine mass.

PMID- 7636417
TI  - The curve of the cervical spine: variations and significance.

PMID- 7636418
TI  - Conceptual and moral disputes about futile and useful treatments.
AB  - A series of cases have crystallized disputes about when medical treatments are
      useful or futile, and consequently about the doctor-patient relationship,
      resource allocation, communication, empathy, relief of suffering, autonomy,
      undertreatment, overtreatment, paternalism and palliative care. It is helpful to
      understand that utility and futility are complimentary concepts and that
      judgments about whether treatments are useful or futile in the contested cases
      have common features. They are: (1) grounded in medical science, (2) value laden,
      (3) at or near the threshold of utility, and (4) burdensome. No schema for line
      drawing escapes borderline cases and we should focus upon justification of the
      empirical, ethical and evaluative components underlying these judgments, rather
      than make an arbitrary decision about whether doctors, patients or societal
      consensus should be the final arbiter.

PMID- 7636419
TI  - Is futility a futile concept?
AB  - This paper distinguishes four major types of futility (physiological, imminent
      demise, lethal condition, and qualitative) that have been advocated in the
      literature either in a patient dependent or a patient independent fashion. It
      proposes five criteria (precision, prospective, social acceptability, significant
      number, and non-agreement) that any definition of futility must satisfy if it is
      to serve as the basis for unilaterally limiting futile care. It then argues that
      none of the definitions that have been advocated meet the criteria, primarily
      because their proponents have not paid sufficient attention to the problematic
      nature of the data supporting the use of their definitions.

PMID- 7636420
TI  - Towards a just, courageous, and honest resolution of the futility debate.
AB  - This essay discusses the history of the "futility debate" and the motives that
      sometimes prompt health care professionals, health care providers, patients, and
      surrogates to take different sides in it. Changes in the health care system,
      financial responsibility shifts, technical medical advances, and medical care
      rationing are analyzed as contributors to the futility debate. So too are
      variations in the definition of futility examined as part of the current
      controversy. The respective attitudes of professionals, providers, patients, and
      surrogates in accepting the goals, capabilities, and limits of medicine are also
      explored. In particular, the lack of honest communication between health care
      professionals/health care providers on the one hand and patients/surrogates on
      the other is acknowledged as a major roadblock in the building of care-focused
      futility policies. Finally, various initial attempts of hospitals to create
      futility guidelines are evaluated in order to detect problem areas and to suggest
      lines of improvement.

PMID- 7636421
TI  - From futility to triage.
AB  - Basic disagreements about what makes human life valuable hinder use of the
      concept of futility to decide whether it is appropriate to continue life support
      for one in a permanent state of unconsciousness, or to provide intensive medical
      care to one in the last stages of a terminal illness (the "paradigm cases").
      Triage planning (the process of establishing criteria for health care
      prioritization) is an attractive alternative framework for addressing the
      paradigm cases. Triage planning permits society to see the cases in the context
      of diverse moral perspectives, limited resources, and competing health care
      demands. Furthermore, at least one essential question posed by the paradigm cases
      is whether treatment is wasteful, and triage planning is a useful model for
      identifying and eliminating wasteful medical care. The authors describe how
      triage planning can be implemented to address the paradigm cases, and conclude
      that it offers one way of moving debate about these cases beyond futility.

PMID- 7636422
TI  - The physician's authority to withhold futile treatment.
AB  - The debate over futility is driven, in part, by physicians' desire to recover
      some measure of decision-making authority from their patients. The standard
      approach begins by noting that certain interventions are futile for certain
      patients and then asserts that doctors have no obligation to provide futile
      treatment. The concept of futility is a complex one, and many commentators find
      it useful to distinguish 'physiological futility' from 'qualitative futility'.
      The assertion that physicians can decide to withhold physiologically futile
      treatment generates little controversy. The claim that they can withhold
      qualitatively futile treatment runs afoul of standard objections to medical
      paternalism. There is reason to believe that the conceptual distinction will not
      be maintained in clinical practice. This paper contends that the scientific data
      which would support a physician's unilateral decision to withhold physiologically
      futile treatment also provide support for an institutional policy restricting
      access to the treatment. The data the doctor uses to take decision-making power
      out of the hands of the patient can be used by the administrator to take power
      out of the hands of the doctor. While this loss of power is unproblematic, there
      is reason to believe that the ambiguity in the term 'futility' will allow a much
      greater loss of physicians' power.

PMID- 7636423
TI  - Gonadotrophin secretion revisited. How many ways can FSH leave a gonadotroph?
AB  - In summary, gonadotrophs make and secrete many biologically active proteins, some
      of which participate in autocrine regulation of gonadotrophin, and particularly
      FSH, secretion. This essay focuses on different vehicle(s) for secretion of
      protein products as one way that the gonadotroph might control secretion of the
      two gonadotrophins. Gonadotrophs phasically secrete LH and (proportionately less)
      FSH via secretory granules in response to an increase in intracellular Ca2+, but
      also secrete FSH without LH by a distinct pathway. The latter is tonically
      regulated by not only activin, but also inhibin and follistatin, at least partly
      at the level of FSH synthesis. Thus GnRH-independent secretion of FSH may
      masquerade as a second form of 'regulated' secretion through its linkage with FSH
      synthesis. Three major types of vacuole that possibly mediate gonadotrophin
      secretion have been identified in gonadotrophs: the small, dense core secretory
      granule that is rich in LH; a larger, more diffuse granule that is rich in FSH;
      and the much smaller, synaptic vesicle-like vacuole that contains no identifiable
      gonadotrophin. Which of these subserves the tonically regulated, GnRH-independent
      pathway for secretion of FSH without LH has not yet been determined. It is
      unlikely to be the small granule, because of its preponderance of LH. It may be a
      form of synaptic vesicle-like vacuole, which is immunocytochemically 'silent'
      with respect to FSH, or the FSH-rich larger form of secretory granule, for which
      a specialized, constitutive-like secretory function has not yet been
      assigned.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7636424
TI  - IGF-I and serine protease inhibitor 2.1 nuclear transcript abundance in rat liver
      during protein restriction.
AB  - Restriction of dietary protein consumption of young male rats results in
      decreased growth velocity and a reduction in the abundance of hepatic IGF-I mRNA.
      It is not known whether the reduction of IGF-I mRNA abundance in the liver of
      protein-restricted rats results from a decrease in IGF-I gene transcription. In
      the present study, three experiments were performed with 4-week-old male rats to
      examine the effect of protein restriction on IGF-I gene transcription in liver.
      In these experiments, we monitored IGF-I nuclear transcripts (pre-mRNA) within
      total cellular RNA using a ribonuclease protection assay. In the first
      experiment, a consistent decrease in IGF-I mRNA from animals fed isocaloric diets
      containing 20% (control), 12%, 8% and 4% protein (dietary effect, P < 0.001) was
      not paralleled by a decrease (P > 0.50) in IGF-I pre-mRNA. Two additional
      experiments examining the effect of 4% vs 20% protein diets yielded comparable
      results. Pooled results from these two studies (n = 12/treatment) demonstrated
      that a 64% reduction (P < 0.0001) in IGF-I mRNA abundance was not accompanied by
      a decrease in IGF-I pre-mRNA (1.17 vs 1.31 +/- 0.21 image density units for 4%
      and 20% protein treatments). Unlike IGF-I, the abundance of carbamyl phosphate
      synthetase-I (CPS-I) pre-mRNA and mRNA was comparably reduced (approximately 70%,
      P < 0.001), indicating that the decrease in mRNA of this urea cycle enzyme during
      protein restriction occurs predominantly by a transcriptional mechanism. A common
      feature of all experiments was a pronounced variability in the expression of
      hepatic IGF-I pre-mRNA among animals, which was not diet specific. To test
      whether the variability in IGF-I gene transcription was correlated with
      variability in the transcription of another gene that is regulated by GH, we
      quantified the abundance of nuclear transcripts for the serine protease inhibitor
      2.1 (SPI 2.1) gene. A positive association (r = 0.81, P < 0.0001) between SPI 2.1
      and IGF-I nuclear transcripts was demonstrated. The correlation between IGF-I and
      SPI 2.1 transcripts was specific, because the quantity of IGF-I and CPS-I nuclear
      transcripts was not correlated in this study. Although transcription of the IGF-I
      and SPI 2.1 genes was similar, the abundance of SPI 2.1 mRNA was not altered by
      protein deprivation.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7636425
TI  - Anti-idiotypic antibody as an oestrogen mimetic: removal of Fc fragment converts
      agonist to antagonist.
AB  - Previous studies indicated that the anti-idiotypic antibody (clone 1D5) caused an
      increase in uterine creatine kinase (CK) activity when administered in vivo to
      immature female rats, indicating that the antibody has oestrogenic-like activity.
      It was, therefore, of interest to investigate the structural requirements of
      clone 1D5 to act as an oestrogen mimetic in an in vitro model system. In the
      present study, the effect of clone 1D5 and its proteolytic fragments, F(ab')2,
      Fab' and Fc on CK activity was examined in cultured skeletal cells having
      functional oestrogen receptor (ER). Incubation of female-derived calvaria cells
      or epiphyseal cartilage cells with clone 1D5 (8.33 nM) or oestradiol (E2) (30 nM)
      for 24 h caused a significant increase in CK activity, indicating that clone 1D5
      acted as an agonist. On the other hand, incubation of male-derived calvaria cells
      devoid of a functional ER with clone 1D5 or E2 did not have any effect on CK
      activity. Incubation of female-derived calvaria cells with clone 1D5 and E2 did
      not result in any further increase in CK activity, whereas dihydrotestosterone
      (DHT) did not alter the response to clone 1D5. The CK response to clone 1D5, in
      female-derived calvaria cells was time- and dose-dependent and could be inhibited
      in a dose-dependent manner by the oestrogen antagonist tamoxifen. In contrast,
      the proteolytic fragments of clone 1D5, the F(ab')2 dimer (12 nM) and the Fab'
      monomer (24 nM), and the Fc fragment (28 nM) did not have E2-like activity in
      these cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7636426
TI  - Consistent GH responses to repeated injection of GH-releasing hexapeptide (GHRP
      6) and the non-peptide GH secretagogue, L-692,585.
AB  - GH release is normally stimulated by the naturally occurring GH-releasing factor
      (GRF). However, smaller GH-releasing peptides (GHRPs) and non-peptide analogues
      have been described which stimulate GH release in animals and man. Although these
      compounds release GH in vitro, their in vivo activity in conscious animals has
      proved more difficult to study since the GH responses are variable, and prone to
      desensitization. We now compare the GH-releasing properties of GHRP-6 and a novel
      benzolactam GH secretagogue L-692,585 using chronically cannulated guinea pigs
      and automated blood micro-sampling to study the effects of repeated exposure to
      these secretagogues. L-692,585 was approximately tenfold less potent than GHRP-6
      for GH release, but it synergized strongly with GRF. Serial injections of GRF,
      GHRP-6 or L-692,585 at intervals of 60 or 90 min produced variable GH release
      which followed a cyclic pattern of responsiveness. Prolonging the pulse interval
      to 3 h produced more regular responses to both GHRP-6 and L-692,585. Continuous
      i.v. infusion of low doses of either secretagogue elicited an initial GH release,
      and amplified the spontaneous GH secretory pattern over the next 6 h. We conclude
      that L-692,585 and GHRP-6 share similar in vivo, their in vivo activity in
      conscious animals has frequent injections is similar for all three secretagogues,
      and is a property of the conscious animal rather than of any secretagogue type.
      More consistent responses can be obtained with less frequent injections that more
      closely match the endogenous GH rhythm, whereas continuous exposure to these
      secretagogues leads to amplified endogenous secretion. Our results show that the
      interpretation of in vivo effects of these peptide and non-peptide secretagogues
      will need to take account of their interaction with the endogenous mechanisms
      governing GH release.

PMID- 7636428
TI  - Luteolytic and antiluteolytic effect of the antiprogestagen RU486 in
      pseudopregnant rats.
AB  - To study the effects of the antiprogestagen RU486 on luteal activity in
      pseudopregnant rats, adult female rats made pseudopregnant by sterile copulation
      were given daily injections with oil vehicle or with RU486 (2 mg/day) either
      during the entire period of pseudopregnancy (day 1 till day 14) or during the
      second half of pseudopregnancy (day 8 till day 14). Blood was taken every other
      day to measure serum concentrations of progesterone. At autopsy, on day 15, the
      weights of ovaries, isolated corpora lutea and pituitary glands were recorded. In
      a second study using the same experimental protocol, blood was taken via a
      jugular vein cannula on days 8, 9, 10 and 11 after induction of pseudopregnancy;
      on each of these days blood samples were taken at 0700, 0800 and 0900 h, and at
      1700, 1800 and 1900 h to measure plasma concentrations of prolactin, LH and
      progesterone. Administration of RU486 from day 1 of pseudopregnancy onwards had
      no effect on the increasing concentrations of serum progesterone during the first
      half of pseudopregnancy. Thereafter progesterone concentrations of serum
      progesterone during the first half of pseudopregnancy. Thereafter progesterone
      concentrations increased further in RU486-treated rats whereas they decreased in
      oil-treated pseudopregnant rats. Administration of RU486 from day 8 of
      pseudopregnancy onwards resulted in a decline in progesterone concentrations in
      serum on day 10 followed by ovulation on day 11. Plasma LH concentrations in rats
      treated with RU486 from day 1 of pseudopregnancy were higher than those in oil
      treated rats on days 8, 9, 10 and 11.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7636427
TI  - Characteristics of the binding of 32P-labelled human relaxins to the human fetal
      membranes.
AB  - The two human relaxin genes termed H1 and H2 are expressed in the choriodecidua
      and placenta and have been proposed to act via specific receptors as local
      modulators of collagenolysis in the fetal membranes. Such receptors have been
      inferred, but not demonstrated, from studies of the effect of adding exogenous
      relaxin to these tissues. Thus conditions were optimized for the binding of 32P
      labelled human relaxin H2 to membrane-enriched particulate fractions of human
      fetal membranes, amnion and chorion, with adhering decidua. The membrane protein
      concentration was optimal at 250 micrograms, when incubated at 27 degrees C for
      60 min, at pH 7.5 with Mn2+ and Mg2+ ion concentrations of 2.0 mM. Incubation of
      membrane particulate fractions with increasing amounts of labelled relaxin H2
      suggested the presence of a single class of binding sites with an affinity
      constant (Ka) of 2.15 nM. The binding was primarily to the chorion and decidua
      with very little to the amnion layer. The competition for binding of the 32P
      labelled human relaxin H2 with unlabelled relaxin H2 gave an IC50 of 28 pM, while
      an IC50 of 60 pM and 280 pM was obtained for relaxin H1 and porcine relaxin
      respectively. In contrast, unlabelled guinea-pig relaxin inhibited this binding
      by only 10% even at a 1000-fold greater concentration than H2, and human
      recombinant insulin failed to inhibit even at a million-fold concentration of
      unlabelled relaxin H2. Relaxins H2 and H1 can readily displace the binding of
      either 32P-labelled human relaxins H1 or H2 and gave very similar displacement
      curves.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7636429
TI  - Pituitary-adrenal function in the immature ovine foetus.
AB  - Pituitary-adrenal responses to intravenous infusion of ovine corticotrophin
      releasing hormone (oCRH) or arginine vasopressin (AVP) and to haemorrhage were
      examined in the ovine foetus prior to 90 days of gestation (term 145-150 days).
      In chronically cannulated foetuses (n = 8), between 74 and 84 days of gestation,
      basal ACTH levels were less than 20 pg/ml while cortisol levels were 6.5 +/- 1.5
      nmol/l (mean +/- S.E.M.). Intravenous infusion of oCRH (1 microgram/h for 60 min)
      or AVP (1 microgram/h for 60 min) significantly increased ACTH (P < 0.05 for both
      treatments) and cortisol (P < 0.01 for both treatments) levels, although the
      response to both hormones was modest. In acutely studied foetuses of a similar
      age (70-90 days of gestation, mean 82.0 +/- 1.4 days, n = 7), exteriorization and
      progressive haemorrhage significantly (P < 0.05) elevated ACTH levels from 117.4
      +/- 32.1 pg/ml to a maximal value of 329.2 +/- 112.8 pg/ml, the maximal ACTH
      response corresponding to the removal of a volume of blood equivalent to 6.6 +/-
      1.2% of the pre-haemorrhage body weight. The present study has demonstrated that
      the ovine foetal pituitary, in vivo, is responsive to exogenous and endogenous
      stimuli by mid-gestation and, at this age, although basal cortisol levels are
      low, the foetal adrenal is capable of responding to elevated ACTH levels in the
      short term.

PMID- 7636430
TI  - Plasma clearance, tissue uptake and expression of pituitary peptide
      23/pancreatitis-associated protein in the rat.
AB  - The secretion of peptide 23 by rat pituitary cells is stimulated by growth
      hormone-releasing hormone and inhibited by somatostatin. Recent cloning of the
      cognate cDNA for peptide 23 revealed that it is identical to pancreatitis
      associated protein (PAP). In the present study, the clearance and tissue uptake
      of recombinant peptide 23/PAP in normal adult male rats was assessed. The plasma
      half-life of recombinant peptide 23/PAP was 4.8 +/- 1.4 (S.D.) min. Maximal
      accumulation of radio-labelled peptide 23/PAP was observed in the kidney,
      stomach, small intestine and pancreas whereas negligible uptake was seen in the
      liver, lung or heart. Peptide 23/PAP was detected in a variety of tissue extracts
      using a radioimmunoassay. Extracts of ileum contained the highest concentrations
      of peptide 23/PAP. In situ hybridization analysis showed that peptide 23/PAP mRNA
      was highly expressed in the columnar epithelial cells of ileum, jejunum and
      duodenum. These observations demonstrate that peptide 23/PAP, a protein
      previously thought to be of pituitary origin, is widely expressed in the
      gastrointestinal tract and that it is rapidly removed from the circulation by the
      kidney and by tissues which express peptide 23/PAP.

PMID- 7636432
TI  - The effect of acute immuno-neutralisation of inhibin in ewes during the early
      luteal phase of the oestrous cycle on ovarian hormone secretion and follicular
      development.
AB  - Ewes with ovarian autotransplants received either inhibin antiserum (10 ml i.v.
      raised in sheep against recombinant 32 kDa human inhibin; n = 6) or sheep serum
      (10 ml i.v.; n = 5) on day 3 of the luteal phase with additional daily injections
      (1 ml i.v.) from 48 h after the initial bolus until day 13. Jugular and ovarian
      venous blood samples were taken 4-hourly over days 2-13 of the luteal phase.
      Blood samples were also taken at more frequent intervals (every 10-15 min for 2-3
      h) to examine pulsatile secretory responses from the ovary to endogenous and
      gonadotrophin-releasing hormone-induced (150 ng i.m.) LH pulses on days 4, 6, 8,
      10 and 12 of the luteal phase. Plasma FSH levels, ovarian steroid secretion and
      ovarian follicular development were measured. The ovarian follicle population was
      estimated daily by real time ultrasound scanning. Immunisation against inhibin
      resulted in a 3- to 4-fold increase (P < 0.001) in plasma FSH levels within 8 h
      with levels remaining elevated over controls for 6-7 days. Within 24 h of
      immunisation there was an increase in the number of small ovarian follicles (P <
      0.05) and by 3 days after treatment immunised ewes had 4-6 large ovarian
      follicles/ewe with this increase in the total number of large follicles being
      maintained for the rest of the experimental period (P < 0.05). Mean ovarian
      oestradiol secretion during intensive bleeds was not different from controls 24 h
      after immunisation, but by 3 days after immunisation it was elevated 4- to 5-fold
      (P < 0.001) over controls with this increase being maintained throughout the
      experiment. Similar responses to immunisation against inhibin in androstenedione
      secretion were observed although mean androstenedione secretion was not elevated
      until 7 days after treatment. In vitro antibody titres in immunised ewes remained
      elevated but declined steadily (P < 0.001) over the experimental period. We
      conclude that the initial stimulation of follicle development and ovarian steroid
      secretion following passive immunisation against inhibin can be attributed to
      increased blood FSH. However, the fact that with time FSH declined but increased
      follicle development was sustained, despite maintenance of high circulating
      antibody titres, suggests that on a longer term basis inhibin immunisation may
      stimulate ovarian function by interfering with the modulation of follicle
      development by inhibin at an ovarian level.

PMID- 7636431
TI  - The inhibitory action of melatonin in the ovine pars tuberalis is not dependent
      on changes in plasma membrane potential.
AB  - Treatment of ovine pars tuberalis (oPT) cultures with forskolin activates
      adenylyl cyclase, leading to increased levels of cyclic AMP, activation of
      protein kinase A, phosphorylation of the calcium/cyclic AMP response-element
      binding protein and the increased synthesis and secretion of several proteins.
      Simultaneous treatment with melatonin inhibits or reverses these effects of
      forskolin. In the neonatal rat pituitary, the inhibitory effects of melatonin are
      mediated by changes in membrane potential. This study therefore investigated
      whether the inhibitory action of melatonin in oPT cultures is also dependent on
      the modulation of plasma membrane potential. Treatment of cultures with the
      ionophore valinomycin selectively permeabilised the cell plasma membrane to
      potassium, thereby causing membrane hyperpolarisation. In cultures of oPT,
      valinomycin inhibited in a concentration-dependent manner (maximal effect 2
      microM) the stimulatory action of forskolin (1 microM) on intracellular levels of
      cyclic AMP, indicating that the activity of adenylyl cyclase in this tissue is
      sensitive to hyperpolarisation of the plasma membrane. However, increasing the
      extracellular concentration of potassium from 5 mM to 100 mM, which would
      depolarise the plasma membrane, had no effect on the inhibitory action of
      melatonin (1 microM) in forskolin-stimulated cultures. This indicated that
      melatonin could be effective in cells with sustained depolarisation. To test
      directly whether integrity of the plasma membrane is essential for melatonin to
      inhibit adenylyl cyclase, cultures were treated with the cholesterol-chelating
      agent saponin (50 micrograms/ml). Saponin increased cellular permeability to
      trypan blue and enhanced the release of the cytoplasmic enzyme lactate
      dehydrogenase to the extracellular medium, demonstrating that cell plasma
      membranes had been permeabilised, thereby abolishing membrane polarity.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7636433
TI  - Effects of inhibin-related peptides and oestradiol on androstenedione and
      progesterone secretion by bovine theca cells in vitro.
AB  - Primary monolayer cultures of bovine theca cells isolated from pooled ovarian
      follicles (3-10 mm diameter) were used to examine the effects of various
      granulosa cell-derived substances on basal and luteinizing hormone (LH)-induced
      androgen and progesterone secretion. After an overnight pretreatment period,
      cells were incubated with a range of treatments including LH, oestradiol-17 beta,
      inhibin, activin and follistatin. Media were collected after 48 h and assessment
      of androstenedione and progesterone secretion made by radioimmunoassay. Addition
      of LH (5-50 ng/ml) to the cells resulted in a dose-dependent stimulation of both
      androstenedione (2.5- to 3-fold rise; P < 0.01) and progesterone (approximately
      1.6-fold rise; P < 0.001) production. Secretion of androstenedione was also
      raised (up to 5-fold; P < 0.001) by addition of oestradiol-17 beta (0.3-300
      ng/ml), whilst levels of the androgen in the presence of both LH (20 ng/ml) and
      oestradiol (300 ng/ml) were up to 12-fold higher (P < 0.001) than control values.
      In contrast, oestradiol treatment inhibited by up to 50% both basal (P < 0.001)
      and LH-stimulated (P < 0.001) secretion of progesterone. Exposure of cells to
      purified bovine inhibin (5-125 ng/ml) consistently raised androstenedione
      secretion by up to 42% over basal levels (P < 0.001). Inhibin also enhanced both
      LH-stimulated (approximately 35%; P < 0.001) and oestradiol-stimulated
      (approximately 20%; P < 0.05) secretion of androstenedione. In direct contrast,
      treatment of theca cells with human recombinant activin-A (1-50 ng/ml) inhibited
      both LH-stimulated (approximately 50%; P < 0.001) and oestradiol-stimulated
      (approximately 30%; P < 0.005) androstenedione secretion. Activin also reversed
      the positive effect of inhibin on basal (P < 0.01), LH-stimulated (P < 0.001) and
      oestradiol-stimulated (P < 0.001) androstenedione secretion, though activin alone
      did not affect basal steroid output. Simultaneous addition of human recombinant
      follistatin reversed the inhibitory effects of activin on LH- and oestradiol
      induced androstenedione secretion but did not modify the effects of inhibin.
      Follistatin alone did not alter either basal or LH-stimulated androstenedione
      output. Neither basal nor LH-stimulated secretion of progesterone were
      consistently affected by inhibin, activin or follistatin. As well as confirming
      the stimulatory effects of both LH and oestradiol on bovine thecal cell androgen
      production, these observations are indicative of opposing intrafollicular
      paracrine roles for granulosa cell-derived inhibin and activin in modulating
      thecal cell responses to gonadotrophins and steroids in the bovine
      ovary.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7636434
TI  - Divergent effects of gonadotrophin-releasing hormone (GnRH) analogue and
      authentic GnRH on the anterior pituitary gland of rats with restricted feeding.
AB  - The effects of gonadotrophin-releasing hormone analogue (GnRHa; buserelin) on the
      pituitary function and morphology of food-restricted rats were compared with
      those of authentic GnRH. After adult female rats had been restricted to 10 g
      food/day for 60 days, various doses of GnRHa (10 ng, 100 ng and 1 microgram) or
      GnRH (10 micrograms) were administered either daily for 7 days or twice a week
      for 4 weeks from day 61 of the period of underfeeding. Underfeeding brought about
      a decrease in the pituitary gonadotrophin content, serum levels of gonadotrophins
      and oestradiol, and the number and size of both LH- and FSH-positive pituitary
      cells. Daily and/or twice-weekly administration of authentic GnRH to underfed
      rats produced an increase in pituitary and serum gonadotrophin levels and the
      number and size of both LH- and FSH-positive pituitary cells. The administration
      of GnRHa daily for 7 days increased serum gonadotrophin levels, while it produced
      a reduction in the pituitary gonadotrophin content and number and size of both LH
      and FSH-positive pituitary cells in a dose-dependent manner. Twice-weekly
      administration of GnRHa also produced an elevation of serum gonadotrophin levels
      and reduction of pituitary gonadotrophin content, although it did not affect the
      numbers and areas of LH- and FSH-positive pituitary cells. A GnRH loading test
      performed after the GnRHa treatment showed that the GnRHa treatment performed in
      this study did not produce down-regulation of the GnRH receptor. Thus, it can be
      concluded that the gonadotrophin-synthesizing activity of GnRHa is weaker than
      that of authentic GnRH, or that GnRHa may preferentially exert gonadotrophin
      releasing activity rather than gonadotrophin-synthesizing activity in the
      anterior pituitary of underfed rats.

PMID- 7636435
TI  - Epidermal growth factor stimulates cell proliferation and inhibits iodide uptake
      of FRTL-5 cells in vitro.
AB  - In accordance with the available data most authors conclude that epidermal growth
      factor (EGF) has very little or no effect on FRTL-5 cells. This has been viewed
      as a serious handicap of this cell line. In the present study we cultivated three
      strains of FRTL-5 cells from different sources and assessed their response to EGF
      with regard to proliferation, function and differentiation. Cell proliferation
      was assessed by counting in a Coulter cell counter after culturing cells at
      suboptimal conditions in well plates. Cell function was studied by measuring
      iodide uptake. Cell differentiation was examined immunocytochemically by staining
      monolayer cultures for thyroglobulin (Tg) and EGF receptor (EGFr) as well as
      morphologically by microscopical evaluation of monolayer cultures. All three FRTL
      5 cell lines investigated express EGFr. In two wild type FRTL-5 cell lines EGF
      stimulates growth, an effect that is enhanced by the presence of TSH, and
      partially inhibits iodide uptake. A third mutated strain of FRTL-5 cells does not
      respond to EGF. Tg expression can be demonstrated immunocytochemically in EGF
      treated cells as well as in controls. Morphologically, in monolayer culture EGF
      treated cells cannot be distinguished from controls. Contrary to previous
      reports, these studies demonstrate EGF effects on FRTL-5 cells that are
      consistent with EGF effects established in other thyroid follicular cells.

PMID- 7636436
TI  - Luminal glucagon-like peptide-1(7-36) amide-releasing factors in the isolated
      vascularly perfused rat colon.
AB  - Glucagon-like peptide-1 (GLP-1) is released from endocrine cells of the distal
      part of the gut after ingestion of a meal. GLP-1 secretion is, in part, under the
      control of hormonal and/or neural mechanisms. However, stimulation of the colonic
      L cells may also occur directly by the luminal contents. This was examined in the
      present study, using an isolated vascularly perfused rat colon. GLP-1
      immunoreactivity was measured in the portal effluent after luminal infusion of a
      variety of compounds which are found in colonic contents (nutrients, fibers, bile
      acids, short-chain fatty acids (SCFAs)). Oleic acid (100 mM) or a mixture of
      amino acids (total concentration 250 mM), or starch (0.5%, w/v) did not increase
      GLP-1 secretion over basal value. A pharmacological concentration of glucose (250
      mM) elicited a marked release of GLP-1 which was maximal at the end of infusion
      (400% of basal), while 5 mM glucose was without effect on secretion. Pectin
      evoked a dose-dependent release of GLP-1 over the range 0.1-0.5% (w/v) with a
      maximal response at 360% of basal when 0.5% pectin was infused. Cellulose or gum
      arabic (0.5%) did not modify GLP-1 secretion. The SCFAs acetate, propionate or
      butyrate (5, 20 and 100 mM) did not induce a significant release of GLP-1. Among
      the four bile acids tested, namely taurocholate, cholate, deoxycholate and
      hyodeoxycholate, the last one was the most potent at eliciting a GLP-1 response
      with a maximal release at 300% and 400% of the basal value when 2 and 20 mM bile
      acid were administered respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7636437
TI  - Differences in carbohydrate composition of FSH preparations detected with lectin
      ELISA systems.
AB  - FSH is a glycoprotein containing N-linked carbohydrates which exhibit a variety
      of forms ranging from mono- to multibranched structures. Variation in
      glycosylation, particularly the degree of terminal sialylation, determines the
      half-life of the hormone and hence its in vivo bioactivity. The glycoform content
      of FSH preparations can differ according to the source (e.g. pituitary, urine),
      cell line (for rDNA-derived material) and selectivity of purification procedures,
      and may create difficulties in the preparation and characterization of standards
      and therapeutic products. In order to develop a simple method to detect changes
      in glycocomposition, an FSH ELISA was modified by the incorporation of lectins of
      recognized sugar specificity, and used to examine the terminal sugar composition
      of ampouled preparations of pituitary, urinary and rDNA-derived FSH. FSH was
      captured with a specific monoclonal antibody (MAb) and detected with either
      biotinylated anti-FSH MAb (ELISA) or the sugar-specific lectins (L-ELISA) from
      Triticum vulgaris (sialic acid, SA), Sambucus nigra (alpha 2,6-linked SA),
      Maackia amurensis (alpha 2,3-linked SA) or Ricinus communis (free terminal
      galactose; GAL). Relative estimates of the amounts of terminal SA, its different
      forms and GAL were derived from the L-ELISA/ELISA data compared with the highly
      sialylated 1st International Standard for pituitary FSH (IS) 83/575. All the FSH
      preparations had less SA than the IS with the ratio of alpha 2,3- and alpha 2,6
      linked SA varying between preparations. The amounts of alpha 2,6-linked SA
      relative to the IS were not significantly different in the urinary and pituitary
      preparations whereas alpha 2,3-linked SA in all preparations was generally less
      than that of the standard.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7636438
TI  - Developmental regulation of androgen receptor in rat ovary.
AB  - Androgen receptor (AR) distribution and developmental regulation in the rat ovary
      were examined by semiquantitative immunohistochemistry. Ovarian AR mRNA levels
      were also determined by Northern analysis of total RNA and compared with the
      levels of cytochrome P450aromatase (P450arom), an established marker of
      preovulatory follicular maturity. Hypophysectomized immature female rats were
      treated with recombinant human (rh)-FSH and/or rh-LH, or human menopausal
      gonadotrophin (HMG). AR was predominantly located in granulosa cells. There was
      no indication of specific AR immunoreactivity in thecal cells, but scattered
      stromal cells did stain positively. In control and LH-treated ovaries, only small
      preantral/early antral follicles were present. Granulosa cells in these follicles
      showed intense AR immunostaining. Treatment with FSH, FSH and LH or HMG
      stimulated varying degrees of preovulatory follicular development. In these
      follicles, the intensity of AR immunostaining progressively declined as
      follicular development progressed. In intact immature rats treated with FSH, the
      abundance of ovarian AR mRNA was significantly decreased to 35% of the control
      value while combined treatment of FSH and LH resulted in further down-regulation
      of AR mRNA expression to 17% of the control value. A decrease in the abundance of
      AR mRNA was accompanied by a simultaneous increase in the abundance of P450arom
      mRNA. Similar results were obtained in hypophysectomized immature rats treated
      with FSH and LH, suggesting an inverse relationship between AR mRNA expression
      and granulosa cell maturity. These results suggest that (1) the AR is most
      abundant in the granulosa cells of rat ovaries and (2) the expression of AR and
      its mRNA are developmentally regulated, being down-regulated during FSH
      stimulated preovulatory follicular development.

PMID- 7636439
TI  - Effects of ovarian steroids on hypothalamic opioid receptor subtypes in
      ovariectomized ewes: regional changes in density and affinity.
AB  - The negative feedback regulation by ovarian steroids of luteinizing hormone
      secretion may be partially mediated by a hypothalamic endogenous opioid
      mechanism. This could be affected by ovarian steroid-regulated changes in
      hypothalamic opioid receptor binding mechanisms. In this report we show that in
      the presence of blocking concentrations of site-selective opioid analogues, [3H]
      diprenorphin homogeneously labelled mu, delta or kappa receptor subtypes
      respectively. Using this receptor binding model, we characterized each opioid
      receptor subtype in the hypothalamic preoptic area and medio-basal hypothalamus
      of ovariectomized (OVX) and OVX plus progesterone- or oestradiol-17 beta (OE2)
      treated ewes. In the preoptic area, progesterone treatment did not influence the
      affinity or capacity of delta or kappa receptor binding sites, but significantly
      reduced mu receptor subtype content (20% less than control) with no statistically
      significant change in affinity. There was no effect of OE2 on either the affinity
      or capacity of each opioid receptor subtype in this area. In the mediobasal
      hypothalamus, progesterone treatment significantly decreased delta subtype
      receptor affinity (22 +/- 11 nM vs control 7 +/- 2 nM) and increased binding
      capacity (78 +/- 9 fmol/mg protein vs control 37 +/- 16 fmol/mg protein). OE2
      treatment had a similar, though more profound effect on affinity (51 +/- 17 nM)
      and binding capacity (139 +/- 26 fmol/mg protein) at the delta receptor binding
      site. There were no significant changes in the affinity or capacity of mu or
      kappa binding sites in the medio-basal hypothalamus. These results indicate that
      steroid hormones modulate hypothalamic opioid receptors in the OVX ewe in a
      receptor subtype- and region-dependent manner.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7636440
TI  - Relative roles of the thyroid hormones and noradrenaline on the thermogenic
      activity of brown adipose tissue in the rat.
AB  - We have assessed the relative contribution of the thyroid hormones and
      noradrenaline (NA) on the calorigenic function of brown adipose tissue (BAT) as
      indicated by GDP binding and O2 consumption of BAT mitochondria. Male Wistar rats
      of 200 g body weight were made hypothyroid with 131I. Groups of animals were
      injected s.c., in divided doses, daily for 10 days, with thyroxine (2
      micrograms/100 g body weight) or tri-iodothyronine (T3; 0.3 microgram/100 g body
      weight). Animals were used 7 days after bilateral or unilateral sympathetic nerve
      excision of BAT (Sx). Sham-operated rats were used as controls. In normal rats
      kept at 22 degrees C, GDP binding reached 94 +/- 24 pmol/mg protein; untreated
      hypothyroid rats had normal binding values whereas the T3-treated group showed an
      increased binding. Sx induced a sharp fall in the three groups (P < 0.01). After
      24-h exposure to 4 degrees C GDP binding increased in normal rats to about 410%
      (P < 0.01) whereas binding failed to increase in response to cold in the
      untreated hypothyroid and the T3-treated groups. Sx reduced GDP binding in the
      three groups significantly (P < 0.01). The consumption of O2 by BAT mitochondria
      showed similar variations in response to Sx and to cold exposure as did GDP
      binding. The data indicated that, at room temperature, BAT calorigenesis can
      function without the thyroid hormones, though not without the catecholamines. The
      findings in rats exposed to cold showed that the lack of NA was significantly
      more effective than the lack of thyroid hormones in preventing the BAT
      hyperactive response. This does not negate an active role for T3 in BAT
      calorigenesis.

PMID- 7636441
TI  - The local differential effect of prostacyclin, prostaglandin E2 and prostaglandin
      F2 alpha on mammary blood flow of lactating goats.
AB  - Mammary blood flow (MBF) and milk yield are closely related in dairy ruminants,
      but little is known about the regulation of MBF in vivo. The local effects on MBF
      of injections or continuous infusions into the mammary artery of prostaglandins
      (PG) or indomethacin (an inhibitor of prostaglandins) respectively, were
      investigated in surgically prepared conscious goats. Prostacyclin (PGI2) was
      found to be a potent stimulator of MBF which increased linearly over the dose
      range 50-1000 ng. PGE2 was almost as potent as PGI2 at low doses, but
      tachyphylaxis occurred at doses at and above 100 ng. The response to repeated
      injections of PGE2 quickly declined depending on the dose. PGF2 alpha had no
      effect on MBF. During infusion of indomethacin into the mammary artery MBF was
      reduced markedly, showing that endogenous mammary prostaglandins are involved in
      the regulation of vasodilatation. The results indicate that PGI2 (and to a lesser
      extent PGE2) has an important role in the local regulation of vascular tone in
      the mammary gland.

PMID- 7636442
TI  - Fluid reabsorption and ion transport by the lower Malpighian tubules of adult
      female Drosophila.
AB  - The properties of the Malpighian tubules of Drosophila melanogaster change along
      their length. The upstream main segments secrete K(+)-rich fluid at a high rate.
      From this, the lower tubules reabsorb significant amounts of water and K+. Under
      stimulation, K+ reabsorption is accelerated. In addition, the lower tubules
      acidify the fluid passed to them by the main segments and secrete Ca2+ into it,
      adding to that transported there by the upstream epithelium. In contrast to the
      lumen-positive transepithelial potential difference (TEP) of the main segments,
      the TEP in the lower tubules is much lower and becomes lumen-negative close to
      their downstream junction with the common ureter. We suggest that the role of the
      lower tubule is to reduce the flow of K(+)-rich fluid that passes to the hindgut;
      this allows the hindgut to process the flow of excretory fluid more thoroughly.

PMID- 7636443
TI  - The role of neurohormonal octopamine during 'fight or flight' behaviour in the
      field cricket Gryllus bimaculatus.
AB  - Octopamine has been called the 'fight or flight' hormone of insects. We tested
      this hypothesis by measuring octopamine levels in the haemolymph of field
      crickets after fighting, flying, courting and escape behaviours. Octopamine
      levels in the cricket Gryllus bimaculatus increased during aggressive (agonistic)
      behaviour from baseline levels of 4.5 +/- 2.1 pg microliters-1 haemolymph to 24.3
      +/- 15.2 pg microliters-1 haemolymph, regardless of whether the cricket won or
      lost the encounter. Octopamine levels also increased after 5 min of flying (to
      44.6 +/- 22.3 pg microliters-1) and during courtship. However, crickets did not
      exhibit an increase in their haemolymph octopamine levels after performing an
      escape run. Therefore, neurohormonal octopamine shows some, but not all, of the
      characteristics that would be expected if it were a component of a nonspecific
      'arousal' system. Rather, octopamine may be released as a neurohormone to prepare
      the animal for a period of extended activity or to assist the animal in
      recovering from a period of increased energy demand. Antennal contact with
      conspecifics may provide a sensory cue that results in the release of octopamine
      into the haemolymph.

PMID- 7636444
TI  - Effects of bafilomycin A1 on cytosolic pH of sheep alveolar and peritoneal
      macrophages: evaluation of the pH-regulatory role of plasma membrane V-ATPases.
AB  - The role of plasma membrane V-ATPase activity in the regulation of cytosolic pH
      (pHi) was determined for resident alveolar and peritoneal macrophages (m theta)
      from sheep. Cytosolic pH was measured using 2',7'-biscarboxyethyl-5,6
      carboxyfluorescein (BCECF). The baseline pHi of both cell types was sensitive to
      the specific V-ATPase inhibitor bafilomycin A1. Bafilomycin A1 caused a
      significant (approximately 0.2 pH units) and rapid (within seconds) decline in
      baseline pHi. Further, bafilomycin A1 slowed the initial rate of pHi recovery
      (dpHi/dt) from intracellular acid loads. Amiloride had no effects on baseline
      pHi, but reduced dpHi/dt (acid-loaded pHi nadir < 6.8) by approximately 35%.
      Recovery of pHi was abolished by co-treatment of m theta with bafilomycin A1 and
      amiloride. These data indicate that plasma membrane V-ATPase activity is a major
      determinant of pHi regulation in resident alveolar and peritoneal m theta from
      sheep. Sheep m theta also appear to possess a Na+/H+ exchanger. However, Na+/H+
      exchange either is inactive or can be effectively masked by V-ATPase-mediated H+
      extrusion at physiological pHi values.

PMID- 7636445
TI  - Changes in motoneuron membrane potential and reflex activity induced by sudden
      cooling of isolated spinal cords: differences among cold-sensitive, cold
      resistant and freeze-tolerant amphibian species.
AB  - The effects of sudden cooling of the spinal cord were studied in three species of
      amphibians--a cold-sensitive tropical toad (Bufo marinus), a cold-resistant,
      aquatic, hibernating frog (Rana pipiens, northern leopard frog) and a freeze
      tolerant frog (Rana sylvatica, wood frog). Ventral root (motoneuron) potentials
      were recorded from isolated, hemisected spinal cords of each species mounted in a
      sucrose-gap recording apparatus and superfused with HCO3(-)-buffered Ringer's
      solution at room temperature (21 degrees C). In the toad, sudden cooling to 6-8
      degrees C produced large, sustained motoneuron depolarizations that returned
      slowly to baseline levels and were accompanied by extensive paroxysmal activity.
      Larger, but shorter-lasting, motoneuron depolarizations associated with only a
      limited amount of paroxysmal activity were generated by rapid cooling of the
      leopard frog spinal cord. Small, brief motoneuron depolarizations followed by a
      hyperpolarization, or hyperpolarizations not preceded by depolarizations, were
      seen in cooled wood frog spinal cords. The wood frog displayed a large amount of
      spontaneous motoneuron activity, but little paroxysmal activity in response to
      sudden cooling. Following prolonged cooling, rewarming the spinal cords of all
      three species resulted in motoneuron hyperpolarizations that slowly decayed
      towards the baseline value. The amplitude of the rewarming-induced response was
      larger and longer in toad motoneurons than in leopard frog and wood frog
      motoneurons. At room temperature, a single supramaximal dorsal root stimulus
      evoked a depolarizing ventral root potential in toad and leopard frog motoneurons
      that was decreased in amplitude and prolonged when the spinal cords were cooled
      to 8 degrees C or below. In contrast, at room temperature, the ventral root
      reflex in the wood frog was followed by a distinct hyperpolarization. Cooling the
      wood frog spinal cord only slightly reduced the amplitude of the ventral root
      potential. In contrast, the evoked hyperpolarization was blocked by sudden
      cooling and also by the addition of dihydro-ouabain to the Ringer's solution. The
      motoneuron hyperpolarizations induced by sudden cooling in the wood frog were
      converted to depolarizations when Cl- in the superfusate was replaced with
      isethionate. The depolarizations elicited by sudden cooling were reduced by the
      addition of kynurenate in all three species. A dose-response curve generated by
      short applications of L-glutamate demonstrated that wood frog motoneurons were
      less sensitive than leopard frog motoneurons to L-glutamate. In summary, three
      species of amphibians, differing in their adaptations to the temperature of their
      environments, vary in their responses to sudden reductions in temperature. The
      relationship of these responses to their environmental adaptations remains to be
      determined.

PMID- 7636446
TI  - Adjustment of K' to varying pH and pMg for the creatine kinase, adenylate kinase
      and ATP hydrolysis equilibria permitting quantitative bioenergetic assessment.
AB  - Physiologists and biochemists frequently ignore the importance of adjusting
      equilibrium constants to the ionic conditions of the cell prior to calculating a
      number of bioenergetic and kinetic parameters. The present study examines the
      effect of pH and free magnesium levels (free [Mg2+]) on the apparent equilibrium
      constants (K') of creatine kinase (ATP: creatine N-phosphotransferase; EC
      2.7.3.2), adenylate kinase (ATP:AMP phosphotransferase; EC 2.7.4.3) and
      adenosinetriphosphatase (ATP phosphohydrolase; EC 3.6.1.3) reactions. We show how
      K' can be calculated using the equilibrium constant of a specified chemical
      reaction (Kref) and the appropriate acid-dissociation and Mg(2+)-binding
      constants at an ionic strength (I) of 0.25 mol l-1 and 38 degrees C. Substituting
      the experimentally determined intracellular pH and free [Mg2+] into the equation
      containing a known Kref and two variables, pH and free [Mg2+], enables K' to be
      calculated at the experimental ionic conditions. Knowledge of K' permits
      calculation of cytosolic phosphorylation ratio ([ATP]/[ADP][Pi]), cytosolic free
      [ADP], free [AMP], standard transformed Gibbs energy of formation (delta fG'
      degrees ATP) and the transformed Gibbs energy of the system (delta fG' ATP) for
      the biological system. Such information is vital for the quantification of organ
      and tissue bioenergetics under physiological and pathophysiological conditions.

PMID- 7636447
TI  - Ventilation and pulmonary gas exchange during exercise in the savannah monitor
      lizard (Varanus exanthematicus).
AB  - During exercise, pulmonary gas exchange in reptiles was predicted to differ from
      that in mammals because of their less complex lung structure, which might reduce
      ventilation-perfusion heterogeneity (V/QL) at the expense of pulmonary diffusion
      limitation. To investigate this, the multiple inert gas elimination technique was
      used in six Varanus exanthematicus at rest and during maximal exercise. Trace
      amounts of six inert gases were infused into the external jugular vein and blood
      samples were collected from the pulmonary artery and the left atrium. Mixed
      expired gas samples and ventilatory and metabolic data were acquired. Indices of
      V/QL heterogeneity, calculated using a 50-compartment model, were low at rest
      (log standard deviation of perfusion distribution, logSDQ = 0.39) and increased
      significantly with exercise (logSDQ = 0.78). Oxygen diffusion limitation was
      apparent during exercise and was comparable to reported mammalian values. A
      molecular-mass-dependent limitation, suggesting limited intrapulmonary gas
      mixing, was evident only at rest. An increase in left atrial PO2 from 82mmHg at
      rest to 96 mmHg during exercise was associated with a corresponding decrease in
      PCO2. These data indicate adequacy of pulmonary ventilation and gas exchange for
      metabolic demands in exercising varanid lizards and suggest that less complex
      lung structures are not necessarily linked to increased pulmonary diffusion
      limitation.

PMID- 7636448
TI  - The mode of ATP-dependent microtubule-kinesin sliding in the auxotonic condition.
AB  - Kinesin is a motor protein that converts chemical energy derived from ATP
      hydrolysis into mechanical work to transport cellular components along
      microtubules. We studied the properties of ATP-dependent microtubule-kinesin
      sliding with two different in vitro assay systems. In one assay system, a kinesin
      coated glass microneedle (elastic coefficient, 1-2.5 pN microns -1) was made to
      slide along an axoneme. Using this system, we obtained the relationship between
      the force (= load) on the microneedle and the velocity of microneedle-kinesin
      sliding in the auxotonic condition, in which the load on the microtubule-kinesin
      contacts increased as sliding progressed. The force-velocity curve was upwardly
      convex (maximum velocity Vmax, 0.58 +/- 0.15 microns s-1; maximum isometric force
      P0, 5.0 +/- 1.6 pN) and was similar to that of in vitro actin-myosin sliding in
      the auxotonic condition, suggesting that the two motor protein systems have
      fundamental kinetic properties in common. In the other assay system, an axoneme
      attached to a glass microneedle (elastic coefficient, 4-5 pN microns -1) was made
      to slide on a kinesin-coated glass surface (Vmax, 0.68 +/- 0.17 microns s-1; P0,
      46.1 +/- 18.6 pN). The change in shape of the axoneme indicated an enormous
      flexibility of randomly oriented kinesin molecules.

PMID- 7636449
TI  - Managed care and rural America.

PMID- 7636450
TI  - Training the 'complete physician' for rural America: lessons from the Oklahoma
      City Federal Building bombing.

PMID- 7636451
TI  - Advanced obstetrical training for family physicians: the future hope for rural
      obstetrical care.

PMID- 7636452
TI  - Clinical effectiveness and quality of life with ranitidine vs placebo in
      gastroesophageal reflux disease patients: a clinical experience network (CEN)
      study.
AB  - BACKGROUND: Gastroesophageal reflux disease (GERD), often characterized as
      heartburn, is a highly common presenting complaint to family physicians. This
      study is the first large, prospective, nationwide family practice outpatient
      evaluation of the effectiveness of the histamine (H2)-receptor antagonist
      ranitidine as medical therapy for this disorder. METHODS: This randomized, double
      blind, placebo-controlled, parallel group, 6-week study was designed to evaluate
      the effect of ranitidine on clinical outcomes and quality of life in patients
      with GERD. Eligible patients included those who were at least 18 years old and
      had at least a 3-month history of heartburn or heartburn therapy and a minimum of
      4 days with at least one heart-burn episode in the week preceding the baseline
      visit. Quality-of-life effects were measured using a general health status
      instrument and a previously validated heartburn-specific questionnaire. RESULTS:
      Ranitidine treatment conferred clinically and statistically significant
      reductions in mean heartburn pain scores within the first 24 hours (P < or =
      .001) and mean number of heartburn episodes within the first 48 hours (P < or =
      .001). These reductions were maintained throughout the 6-week trial, during both
      daytime and nighttime. Compared with patients receiving placebo, patients treated
      with ranitidine also used significantly fewer doses of antacids (P < or = .003).
      Further, both ranitidine-treated patients' and their physicians' global
      assessments of decreases in heartburn severity, as well as clinical improvement
      on ranitidine, proved superior to those of controls (P < or = .001). The rate of
      adverse events associated with ranitidine and placebo was low and similar.
      Ranitidine-treated patients had more favorable scores on the general health
      status dimensions of physical functioning, bodily pain, and vitality (P < .05),
      and more favorable scores on all dimensions of the heartburn-specific
      questionnaire (P < .05). CONCLUSIONS: Twice-daily treatment with ranitidine 150
      mg is a valuable therapy for GERD in a typical family practice setting. It
      reduces the frequency and severity of symptoms within the first 24 to 48 hours of
      treatment and diminishes the use of nonprescription antacids while improving the
      quality of life as measured by both a general health status instrument and a
      disease-specific instrument.

PMID- 7636453
TI  - The use of objective measures of asthma severity in primary care: a report from
      ASPN.
AB  - BACKGROUND: The rising incidence of and mortality from asthma have prompted the
      development of practice guidelines for diagnosis and management. A cornerstone of
      these guidelines is the use of objective measures of asthma severity: spirometry
      or peak expiratory flow rates. We studied the extent to which primary care
      clinicians used objective measures of asthma severity. METHODS: Practices
      affiliated with the Ambulatory Sentinel Practice Network in the United States and
      Canada collected data on 490 asthma-related encounters involving 439 patients.
      For each encounter, the practice recorded the availability of the results of
      spirometry, peak expiratory flow rates, oxygenation (arterial blood gas or pulse
      oximetry), and chest radiograph to the clinician. RESULTS: Objective data about
      asthma severity were infrequently available to ASPN clinicians at the time of the
      encounter. In 67.8% of encounters, there was no current or past spirometry
      result, in 55.1% there was no current or past peak flow measurement, and in 74.3%
      there was no current or past determination of oxygenation. Chest radiographs, on
      the other hand, were available for most (64.7%) patients. The lack of objective
      measures was not related to lack of access to the relevant technologies. Most
      practices noted easy access to spirometry (72.2% of practices), peak flow meters
      (72.2%), oxygenation determination (61.1%), and radiography (83.3%). CONCLUSIONS:
      In this study, most primary care clinicians did not have objective data about the
      severity of their patients' asthma at the time of the encounter. This relative
      lack of objective data was not explained by lack of access to the relevant
      technology for determining severity. It may instead reflect the opinion of
      primary care physicians that such information is not necessary in the care of
      these patients.

PMID- 7636454
TI  - Patient preferences for migraine therapy: subcutaneous sumatriptan compared with
      other medications.
AB  - BACKGROUND: This study was conducted to identify, from the patient's perspective,
      the important attributes of a migraine therapy and to assess the performance of
      subcutaneous sumatriptan, aspirin, acetaminophen, and patients' usual therapies
      with respect to these attributes. METHODS: Six hundred forty-eight patients who
      had received subcutaneous sumatriptan (one or two doses, 6 mg per dose, for a
      single migraine episode) or placebo in a clinical trial completed questionnaires.
      RESULTS: According to patients, the four most important attributes of a migraine
      therapy are "how well it works," "how safe it is," "how fast it works," and "side
      effects." The least important attribute is "cost of drug." Subcutaneous
      sumatriptan received significantly more favorable scores than did aspirin,
      acetaminophen, or patients' usual therapies with respect to the attributes of how
      well it works, how fast it works, and number of doses needed to relieve pain.
      Subcutaneous sumatriptan was also rated more favorably than either aspirin or
      patients' usual therapies with respect to side effects. Acetaminophen and aspirin
      were rated significantly more favorably than subcutaneous sumatriptan on the
      attributes "easy to take" and "easy to buy." Asked which drug they would use
      again for migraine, more patients selected subcutaneous sumatriptan than any
      other single medication. More patients also ranked subcutaneous sumatriptan as
      the best overall performer compared with other migraine medications taken in the
      last 12 months. CONCLUSIONS: These data indicate that according to patients'
      preferences, subcutaneous sumatriptan possesses many of the attributes of an
      ideal migraine therapy.

PMID- 7636455
TI  - Infectious asthma: a reemerging clinical entity?
AB  - BACKGROUND: In the primary care setting, patients often report that their asthma
      began after an acute respiratory infection such as bronchitis, pneumonia, or an
      influenza-like illness ("infectious asthma"). Preceding respiratory illnesses
      such as bronchitis and pneumonia are also epidemiologic correlates of asthma in
      both children and adults. These associations suggest the possibility that
      respiratory infection is involved in the initiation of asthma in addition to the
      already acknowledged role of infection in asthma exacerbations. The purpose of
      this study was to investigate whether a history of infectious asthma influenced
      clinical and pulmonary function characteristics of patients with chronic asthma.
      METHODS: Conducted in a community-based primary care practice, this is a clinical
      descriptive study of 92 middle-class patients who had a mean age of 37.7 years
      (standard deviation 15.4 years), a clinical diagnosis of chronic asthma, and
      baseline pulmonary function test results available for analysis. RESULTS: There
      was sufficient history available to classify asthma as infectious in 41 (45%) of
      92 patients. Patients with infectious asthma reported a much shorter duration of
      asthma symptoms than did patients with atopic, occupational, and exercise-induced
      asthma (5.6 vs 13.3 years, P = .001). Nevertheless, patients with infectious
      asthma had significantly worse percentages of predicted FEV1 and FEF25%-75%, both
      before and after bronchodilator therapy. CONCLUSIONS: Infectious asthma was
      common in this primary care setting. Compared with patients with other asthma
      syndromes, those with infectious asthma had worse pulmonary function despite a
      shorter duration of symptomatic disease. Further studies of the cause and
      prognosis of this clinical entity are warranted.

PMID- 7636456
TI  - Firearm injury risk among primary care patients.
AB  - BACKGROUND: Firearm injuries are the eighth leading cause of death in the United
      States. Evidence suggests that availability of guns in the home is associated
      with an increased risk of homicide, suicide, and unintentional injuries and
      fatalities. Our study examined five demographically diverse primary care
      practices in Oregon to determine the extent to which patients and members of
      their households might be at risk for firearm injuries. METHODS: Six hundred and
      four consecutive English-speaking patients who were at least 18 years old and
      seeking care at the five different practices were surveyed. Participants were
      asked about the presence of firearms in the home, methods of storage, history of
      firearm safety training, and history of firearm counseling by their physicians.
      RESULTS: Forty-two percent of respondents reported having at least one firearm in
      the home. In homes with firearms, 48% contained at least one firearm that was
      stored unlocked, and 26% contained at least one firearm stored loaded. Twenty
      percent of homes with children contained at least one unlocked firearm, and 10%
      contained a loaded firearm. Forty-five percent [corrected] of those homes with
      both children and firearms had at least one gun that was stored unlocked, and 25%
      [corrected] contained at least one loaded firearm. Those who reported having had
      formal firearm safety training were no more likely to store their firearms safely
      than those without such training. Only 3% of respondents reported that their
      physician had ever talked with them about gun safety. CONCLUSIONS: Our data
      indicate that a substantial number of patients cared for by primary care
      physicians are at risk for firearm injuries.

PMID- 7636457
TI  - Needle phobia: a neglected diagnosis.
AB  - Needle phobia is a recently defined medical condition that affects at least 10%
      of the population. Because persons with needle phobia typically avoid medical
      care, this condition is a significant impediment in the health care system. The
      etiology of needle phobia lies in an inherited vasovagal reflex of shock,
      triggered by needle puncture. Those who inherit this reflex often learn to fear
      needles through successive needle exposure. Needle phobia is therefore both
      inherited and learned. In a family practice, needle phobia can be managed by
      reassurance and education, avoidance of needles, postural and muscle tension
      techniques, benzodiazepines, nitrous oxide gas, and topical anesthesia applied by
      iontophoresis.

PMID- 7636458
TI  - Minocycline-induced hyperpigmentation.
AB  - A 70-year-old man developed hyperpigmentation of his forearms, hands,
      fingernails, sclerae, ears, and teeth after 9 years of therapy with minocycline
      for acne rosacea. Minocycline is widely used in the treatment of acne vulgaris
      and uncommonly produces the side effect of hyperpigmentation. This effect does
      not appear to be dose-dependent and usually resolves within months to years after
      discontinuation of therapy. Discoloration of adult teeth, however, is generally
      permanent.

PMID- 7636459
TI  - Ranitidine and GERD.

PMID- 7636460
TI  - Risk factors for hip fractures.

PMID- 7636461
TI  - Medical malapropisms: the sequin (sequel).

PMID- 7636462
TI  - More malapropisms.

PMID- 7636463
TI  - More malapropisms.

PMID- 7636464
TI  - More malapropisms.

PMID- 7636465
TI  - Pyogenic granuloma.

PMID- 7636466
TI  - Cholesterol and mortality in older patients.

PMID- 7636467
TI  - Asthma attack triggered by barbecue.

PMID- 7636468
TI  - Cost-effectiveness in medicine.

PMID- 7636469
TI  - Ribosomal frameshifting viral RNAs.

PMID- 7636470
TI  - Epitope mapping of the V3 domain of feline immunodeficiency virus envelope
      glycoprotein by monoclonal antibodies.
AB  - A panel of six IgG monoclonal antibodies (MAbs) was produced by immunizing mice
      with a 22 amino acid synthetic peptide, designated V3.3, of the third variable
      region of feline immunodeficiency virus (FIV) envelope glycoprotein. This peptide
      is known to induce neutralizing antibodies in cats. In ELISA all MAbs reacted
      with purified SDS-disrupted FIV and in flow cytometry all MAbs stained permeated,
      persistently infected FL4 cells but not unfixed FL4 cells; this indicated that
      the MAbs recognize essentially cryptic epitopes of the gp100 V3 loop. By direct
      ELISA using partially overlapping synthetic peptides and by competition binding
      studies, the anti-V3.3 MAbs were shown to detect at least four distinct epitopes,
      two located in the amino-terminal half and two in the carboxy-terminal half of
      the sequence. When tested for neutralizing activity by the syncytium inhibition
      assay in Crandell feline kidney cells, all anti-V3.3 MAbs neutralized FIV at high
      dilution. However, at low dilution two MAbs exhibited much less neutralizing
      activity. These results indicate that the V3 region of FIV contains multiple
      epitopes involved in neutralization.

PMID- 7636471
TI  - Impact of natural sequence variation in the V2 region of the envelope protein of
      human immunodeficiency virus type 1 on syncytium induction: a mutational
      analysis.
AB  - Several studies have demonstrated a functional role for the V1-V2 region of the
      human immunodeficiency virus type 1 (HIV-1) envelope surface glycoprotein gp120
      in the membrane fusion processes underlying viral entry and syncytium induction.
      In a study with chimeric primary envelope genes, we have previously demonstrated
      that the exchange of V2 regions was sufficient to transfer syncytium-inducing
      capacity to a non-syncytium-inducing envelope protein. The exchanged V2 regions,
      comprising a number of variable amino acids, conferred changes to both the
      predicted secondary structure and to the net positive charge of the V2 loops. In
      a syncytium-forming assay based on transient envelope protein expression in CD4+
      SupT1 cells, we have extended this observation by mutating the variable positions
      of the V2 region to determine the relative contribution of individual amino acids
      to syncytium formation. It can be shown that simultaneous mutation of multiple
      amino acids is needed to interfere with the V2 region-determined syncytium
      inducing phenotype. Single amino acid changes either influencing charge of
      predicted secondary structure of the V2 loop proved to be insufficient to abolish
      V2 region-controlled syncytium formation. This robust V2 organization may allow
      the virus to accumulate mutations, while retaining its biological phenotype.

PMID- 7636472
TI  - Mapping of the intermolecular association of human T cell leukaemia/lymphotropic
      virus type I p12I and the vacuolar H+-ATPase 16 kDa subunit protein.
AB  - The p12I protein, a small hydrophobic protein encoded by the human T cell
      leukaemia/lymphotropic virus type I pX region, contains a proline-rich region
      located between two putative transmembrane (TM) domains. The p12I protein is
      associated with cellular endomembranes, and physically binds to the 16 kDa
      subunit of the vacuolar H+-ATPase proton pump. To investigate the nature of the
      16 kDa and p12I interaction and to determine the oncogenic domain of p12I, we
      constructed p12I mutant proteins in which various portions of the TM domains were
      deleted, as well as p12I mutant containing a single amino acid substitution.
      These mutants were tested for binding to the 16 kDa subunit of the vacuolar H+
      ATPase in HeLa/Tat cells and for the capability to potentiate transformation by
      bovine papillomavirus type 1 E5 oncoprotein in mouse C127 cells. The results
      indicated that both TM domains of the p12I protein were dispensable for its
      interaction with the 16 kDa protein, whereas partial or complete deletion of the
      proline-rich region resulted in decreased or no binding of the p12I protein to
      the 16 kDa subunit. Immunofluorescence analysis of HeLa/Tat cells transfected
      with the p12I mutants showed that deletion of the proline-rich region did not
      alter the subcellular localization of these mutant p12I proteins, suggesting
      direct involvement of the proline-rich domain in binding rather than the failure
      of these p12I mutants to reach the appropriate cellular compartment. Mapping of
      16 kDa subunit mutants in binding with p12I protein suggested that molecular
      determinants located between the second and third TM domain of the 16 kDa protein
      might be involved in this interaction. Finally, most of the p12I mutants lost the
      ability to potentiate transformation of C127 cells indicating that binding of
      p12I to the 16 kDa subunit does not directly correlate with oncogenicity.

PMID- 7636473
TI  - Construction of a herpes simplex virus/varicella-zoster virus (HSV/VZV) thymidine
      kinase recombinant with the pathogenic potential of HSV and a drug sensitivity
      profile resembling that of VZV.
AB  - A recombinant of herpes simplex virus (HSV) was constructed in which the HSV
      thymidine kinase (TK) gene was deleted and the varicella-zoster virus (VZV) TK
      gene was introduced into the US5 region under the control of the human
      cytomegalovirus IE promoter. Infection with the recombinant (R18) led to the
      induction of TK although the kinetics of synthesis resembled those of a 'late'
      gene product. The recombinant was virulent in the zosteriform mouse model with
      the pattern of pathogenesis similar to that of wild-type HSV-1. The sensitivity
      of the recombinant to several nucleoside analogues was assessed and in most cases
      (BVaraU, ACV and GCV) it resembled VZV rather than HSV. The enhanced sensitivity
      of the recombinant to BVaraU compared with wild-type HSV resulted in a far
      greater response to treatment with BVaraU as assessed in the mouse model.

PMID- 7636474
TI  - Identification and characterization of the frog virus 3 DNA methyltransferase
      gene.
AB  - Cytosine DNA methyltransferases (MTases) first recognize specific nucleotide
      sequences and then transfer a methyl group from S-adenosylmethionine to cytosine.
      This division of function is reflected in five highly conserved motifs shared by
      cytosine MTases. The region containing the first four motifs is responsible for
      the catalytic function whereas the region containing the fifth motif V provides
      specificity of binding to DNA. In at least one case, two separate proteins, one
      containing the first four motifs and the second containing the last motif combine
      to provide full functional activity. In the frog virus 3 (FV3) genome we have
      identified an open reading frame (ORF) whose deduced amino acid (aa) sequence
      contains motifs characteristic of prokaryotic as well as eukaryotic MTases. The
      ORF consists of 642 bp which codes for a protein of 214 aa with a predicted
      molecular mass of 24.8 kDa. This ORF contains the first four highly conserved
      motifs of cytosine MTases but the fifth motif, responsible for DNA binding
      specificity, is missing. Presumably, FV3 MTase is composed of two subunits.
      Northern blot analysis showed that the putative MTase ORF is transcribed into two
      transcripts belonging to the delayed-early class of FV3 messages. These two
      transcripts appear to be initiated at two different start sites but terminate in
      the same 3' region of the gene. The transcription start sites are not preceded by
      any known promoter sequences, but two regions of hyphenated dyad symmetry are
      present at the 3' end of the message. A protein with a molecular mass of
      approximately 28 kDa was synthesized by a rabbit reticulocyte lysate programmed
      with capped runoff transcripts from the cloned gene, suggesting that the ORF can
      be transcribed into a message coding for a viral protein. Overall, our results
      suggest that we have identified a gene for a subunit of MTase in the FV3 genome.

PMID- 7636475
TI  - Epidermal growth factor induction of human papillomavirus type 16 E6/E7 MRNA in
      tumor cells involves two AP-1 binding sites in the viral enhancer.
AB  - The early genes E6 and E7 from human papillomaviruses (HPVs) play a key role in
      the development of cervical cancer. Modulation of E6 and E7 gene expression may
      alter tumour progression; therefore, modifiers of viral transcription such as
      hormones or growth factors are potential risk factors in cancer development. We
      have analysed the effects of epidermal growth factor (EGF) on E6/E7 mRNA from
      human papillomavirus type 16 (HPV-16) by Northern blot in two cell lines, SiHa
      cervical carcinoma cells, and HPK IA, an HPV-16-immortalized keratinocyte cell
      line. E6/E7 mRNA is EGF-inducible in SiHa cells, with the earliest response after
      2 h. In contrast, in HPK IA cells no increase in E6/E7 RNA is observed,
      suggesting a differential EGF response of viral transcription in tumour cells
      compared with keratinocytes. We demonstrate that the cell type-specific HPV-16
      enhancer is a target of EGF-induced signals, as its activity is amplified by EGF
      in SiHa cell transfections. However, when transfected into HPK IA keratinocytes,
      the viral enhancer shows no EGF response. The enhancer contains two binding sites
      for the transcription factor AP-1, a potential mediator of the EGF signalling
      cascade. Enhancer subfragments with single AP-1 binding sites are also EGF
      responsive in SiHa cells. Mutating either AP-1 site in the complete enhancer
      decreases the EGF response, whereas a double mutation causes a complete loss of
      EGF regulation, suggesting that the EGF induction of HPV-16 early transcription
      requires AP-1 activation. We conclude that alterations of EGF responsiveness that
      increase viral oncogene expression may contribute to cervical cancer progression.

PMID- 7636476
TI  - Adenovirus protein-protein interactions: molecular parameters governing the
      binding of protein VI to hexon and the activation of the adenovirus 23K protease.
AB  - A variety of recombinant proteins derived from protein pVI of human adenovirus
      type 2 (Ad2) were analysed for their ability to bind Ad2 hexon in vitro. As pVI
      is also required for activation of the adenovirus-coded protease, the same pVI
      derivatives were assessed for their ability to activate recombinant adenovirus
      coded 23K protease. Two regions, between amino acid residues 48-74 and 233-239 of
      pVI, were required for the interaction with hexon. These regions are highly
      conserved amongst mastadenovirus pVI proteins. Both these regions are capable on
      their own of binding hexon weakly but must be provided in cis for strong hexon
      binding. In addition, we found evidence to indicate than conformation as well as
      sequence was important for good hexon binding in our assays. Authentic processing
      of the appropriate recombinant pVI derivatives, by the recombinant protease, was
      obtained without the addition of other cofactors. These findings are discussed in
      relation to the role of pVI in triggering the adenovirus maturation pathway.

PMID- 7636477
TI  - Investigation of promoter function in human and animal cells infected with human
      recombinant adenovirus expressing rotavirus antigen VP7sc.
AB  - Human adenovirus (Ad) vectors are being used increasingly for a variety of
      applications in vaccination and gene therapy. The ability of vectors to enter
      cells and the efficiency of promoters expressing the therapeutic gene or vaccine
      antigen are critical to the outcome of such experiments. To identify promoters
      which might be suitable for use under a variety of conditions we have
      investigated the expression of a rotavirus antigen, VP7sc, employing several
      commonly used promoters carried in E1-substituted Ad vectors both in cell types
      which support virus replication and in cells which do not. Although not all gene
      constructions were identical, wide variations in promoter function were evident
      even in human 293 cells which support virus replication. The simian virus type 40
      (SV40) early and beta-actin promoters expressed poorly; the SV40 late promoter
      was somewhat better. The human IE94 cytomegalovirus (CMV) promoter and a modified
      Ad major late promoter were best, functioning equally well but with different
      kinetics. In other human cell lines the CMV promoter was more versatile,
      generally providing sustained expression at a significant level, in one case for
      at least 6 days. In addition, as mouse, rabbit and pig models of rotavirus
      infection are under investigation and VP7sc is a vaccine antigen, we also
      investigated the ability of the recombinant adenovirus to infect cells from these
      and other sources. VP7sc expression was detected in several heterologous cell
      types, illustrating the ubiquity of the human Ad receptor and the versatility of
      human Ad as vectors when suitable promoters are used.

PMID- 7636479
TI  - Equine arteritis virus-neutralizing antibody in the horse is induced by a
      determinant on the large envelope glycoprotein GL.
AB  - Complementary DNAs encoding ORFs 2 to 7 equine arteritis virus (EAV) have been
      cloned into the expression vector pGEX to produce glutathione-S-transferase
      fusion proteins. Recombinant proteins were affinity purified and screened in
      ELISA with equine sera to identify immunoreactive polypeptides. The large
      envelope glycoprotein (GL) was identified as the most reactive to EAV-positive
      equine sera and an immuno-dominant epitope was mapped between amino acids 55 and
      98 by subcloning and expression. A fusion protein covering this region and a GL
      specific synthetic peptide (residues 75 through 97) induced EAV-neutralizing
      antibody in vaccinated horses. The defined antigenic region of GL is likely to be
      exposed on the surface of the native EAV virion and consequently may be useful in
      the development of diagnostic tests and vaccines.

PMID- 7636478
TI  - Antigenicity, immunogenicity and passive protection induced by immunization of
      mice with baculovirus-expressed VP7 protein from rhesus rotavirus.
AB  - The major neutralization antigen VP7 of rhesus rotavirus (RRV) was expressed in a
      baculovirus recombinant system. The expressed VP7 showed the same molecular mass
      as native VP7, and was recognized by hyperimmune sera as well as neutralizing and
      non-neutralizing monoclonal antibodies (MAbs) raised against RRV. Intraperitoneal
      administration of the expressed VP7 in mice elicited the production of serum
      antibodies which were able to immunoprecipitate VP7 from RRV-infected cell
      lysates and to neutralize the virus in vitro. Sera from immunized mice competed
      for binding to RRV in an ELISA with both neutralizing and non-neutralizing MAbs
      specific for VP7. Using a passive protection model of rotavirus disease,
      vaccination of mice with the recombinant VP7 induced partial protection from
      infection. These results suggest that the baculovirus-expressed VP7 may be useful
      in priming a protective immune response to rotavirus infection.

PMID- 7636480
TI  - Cytotoxic T cell response to Mengo virus in mice: effector cell phenotype and
      target proteins.
AB  - The Mengo virus specific cytotoxic T lymphocyte (CTL) response was investigated
      after intraperitoneal infection of mice with the attenuated Mengo virus strain
      vMC24. A high level of CTL activity was detected in spleen cell cultures obtained
      from infected C3H/HeJ (H-2k) or C57BL/6 (H-2b) mice after a secondary in vitro
      stimulation with Mengo virus-infected cells. The CTL activity, which was MHC
      class I-restricted, was shown to be mediated by CD8+ T cells. Recombinant
      vaccinia viruses that expressed capsid proteins VP0, VP1 or VP3 were produced and
      used to identify the protein(s) recognized by the Mengo virus-specific CTLs. In
      both C3H/HeJ and C57BL/6 mice, analysis of CTL activity against target cells
      expressing each capsid protein showed that VP0 was the only capsid protein
      recognized by the CD8+ CTLs. The CTL epitope(s) could be further located in the C
      terminal half of VP0, i.e. in capsid protein VP2. Moreover, using unlabelled
      target cells expressing VP0 as cold competitors, we were able to almost
      completely inhibit recognition and lysis of Mengo virus-infected cells by
      specific CD8+ CTLs. Thus, the CTL response directed against VP2 was
      immunodominant in both C3H/HeJ- and C57BL/6-infected mice.

PMID- 7636481
TI  - Seroepidemiological and molecular evidence for the presence of two H3N8 equine
      influenza viruses in China in 1993-94.
AB  - In May 1993, a severe epidemic of respiratory disease began in horses in Inner
      Mongolia and spread throughout horses in China. The disease affected mules and
      donkeys as well as horses but did not spread to other species, including humans.
      The severity of the disease raised the question of whether the outbreak might
      have been caused by the new avian-like influenza viruses detected in horses in
      China in 1989 or by current variants ofA/equine/Miami/1/63 (H3N8) (equine-2) or
      by a reassortant between these viruses. Antigenic and sequence analysis
      established that all gene segments of the influenza virus causing the epidemic
      were of recent equine-2 origin and that the virus was not a reassortant.
      Serological analysis of post-infection horse sera provided evidence for the
      continued circulation of the A/Equine/Jilin/1/89 (Eq/Jilin) (H3N8) avian-like
      viruses in horses in Heilongjiang province with original antigenic sin-like
      responses. It is noteworthy that prior infection with the avian-like Eq/Jilin
      strain did not afford cross-protection against a current equine-2 strain.
      Serological evidence for the continued circulation of the avian-like H3N8
      influenza virus in horses indicates that this virus has probably established
      itself in horses in Asia.

PMID- 7636482
TI  - Cherry virus A: cDNA cloning of dsRNA, nucleotide sequence analysis and serology
      reveal a new plant capillovirus in sweet cherry.
AB  - The nucleotide sequence (7383 nucleotides) of a newly identified member of the
      genus Capillovirus, cherry virus A (CVA), was obtained from cDNA clones. The cDNA
      was generated from dsRNA extracted from plant tissue infected with little cherry
      virus (LCV). Small amounts of LCV dsRNA served as template nucleic acid and
      enabled the construction of a library of which, unexpectedly, 7.5% of the
      recombinant plasmids were specific for CVA. The genome organization of CVA
      resembles that of apple stem grooving virus (ASGV), the type member of the genus
      Capillovirus and is composed of a 266 kDa polyprotein (ORF1), a 52 kDa ORF2
      located within ORF1 and a poly(A) tail. The 266 kDa ORF1 contains all the
      elements of a replication-related protein and has high identity with 'Sindbis
      like' viruses. The ORF encodes the coat protein (CP) in the C-terminal region.
      The 52 kDa ORF2 has high identities with the putative viral cell-to-cell movement
      proteins of capillo- and trichoviruses. The CP was identified in immunoblot
      analysis and estimated to have a molecular mass of 24 kDa. Antiserum was obtained
      by expression of antigens as fusion proteins in Escherichia coli. There is
      significant sequence identity between CVA CP and the corresponding proteins of
      other capillo- and trichoviruses. However, no serological cross-reaction was
      obtained in immunoblot analysis with ASGV, apple chlorotic leafspot trichovirus
      (ACLSV), apple stem pitting virus (ASPV) and cherry mottle leaf virus (CMLV)
      antisera. Flexuous filamentous CVA virions were identified in extracts of sweet
      cherry by immunosorbent electron microscopy (ISEM) and decorated with the
      antiserum to the fusion protein. CVA was identified in three cherry sources of
      different disease status by ISEM, immunoblot analysis and hybridization to dsRNA.
      CVA is not closely related to any of the currently described diseases in cherry
      but it has all the properties of a capillovirus. It is suggested that CVA should
      be classified as a new member of the genus capillovirus.

PMID- 7636483
TI  - The nucleotide sequence and proposed genome organization of oat chlorotic stunt
      virus, a new soil-borne virus of cereals.
AB  - The complete genomic sequence of a new virus, first found infecting oats in
      Wales, UK, has been determined. The genome is a positive-sense ssRNA molecule,
      4114 nucleotides in length, examination of which indicates the presence of four
      ORFs. The first ORF initiating at the 5' terminus (ORF1) encodes a protein with a
      predicted M(r) of 23476 (p23). ORF2 extends through the amber termination codon
      of ORF1 to give a protein with a predicted M(r) of 84355 (p84). The readthrough
      domain of p84 contains amino acid sequence similarities with a number of putative
      RNA-dependent RNA polymerases. ORF3 is in a different reading frame from ORF1/2
      and encodes a protein with an M(r) of 48231 (p48), identified as the coat protein
      by direct peptide sequencing. ORF4 nests within ORF3 but is in a different frame
      from it and codes for a protein with a predicted M(r) of 8220 (p8). Comparisons
      of peptide sequence, particularly within the putative polymerase region and
      within the S domain of the coat protein, highlight similarities with members of
      both the tombusvirus and carmovirus groups. The coat protein region shows most
      similarity with members of the tombusvirus group, whilst the size and predicted
      strategy of the genome seem to be intermediate between that of the carmovirus and
      tombusvirus groups. These features highlight possible evolutionary links with
      each group whilst being distinct from both. We propose the name of oat chlorotic
      stunt for this new virus.

PMID- 7636484
TI  - The complete nucleotide sequence and genome organization of the mite-transmitted
      brome streak mosaic rymovirus in comparison with those of potyviruses.
AB  - A virus isolate, designated as 11-Cal, originating from southern France has been
      identified as an isolate of the mite-transmitted brome streak mosaic rymovirus
      (BrSMV) by serological and morphological properties. BrSMV is a member of the
      genus Rymovirus of the family Potyviridae. The complete nucleotide sequence of
      the RNA genome of BrSMV has been determined. The assembled RNA is 9672
      nucleotides in length, excluding a 3'-terminal poly(A)sequence. The RNA contains
      one open reading frame (ORF) of 9282 nucleotides coding for a polyprotein of 3093
      amino acids. A comparison with typical potyvirus showed that BrSMV has a similar
      genome organization. The predicted cleavage sites of the polyprotein of BrSMV are
      similar to those of potyviruses. Nevertheless, unusual dipeptides are proposed in
      two cases. Based on the proposed location of the cleavage sites nine mature
      proteins are predicted. Specific motifs, described for potyviral polyproteins,
      are almost all present in the polyprotein of BrSMV, too. However, only an
      incomplete zinc-finger motif is present in the potential helper component and the
      motif for aphid transmission in the coat protein is not found. Several alignments
      of amino acid sequences showed less similarity between BrSMV and potyviruses than
      between different potyviruses.

PMID- 7636485
TI  - Nucleotide sequences from tomato leaf curl viruses from different countries:
      evidence for three geographically separate branches in evolution of the coat
      protein of whitefly-transmitted geminiviruses.
AB  - The coat protein (CP) gene-containing circular DNA molecule of an isolate of
      tomato leaf curl geminivirus (ITmLCV; 2749 nt) obtained from southern India, and
      the CP genes of tomato yellow leaf curl geminivirus isolates from Nigeria and two
      regions of Saudia Arabia were sequenced. ITmLCV DNA had the same arrangement of
      ORFs, and the same pattern of repeats in the large intergenic region as is found
      in in DNA-A of other whitefly-transmitted geminivirus (WTGs) from the Old World.
      However, the sequence of ITmLCV DNA and the sequences of its predicted
      translation products differed substantially from those of other WTGs, including
      one isolate obtained from a tomato plant in northern India. Comparison of the
      four CP sequences deduced here with those of 18 WTGs previously studied indicated
      that their relationships can be represented by a tree with three branches that
      are unrelated to plant host species but which contains viruses from the Americas,
      Africa to the Middle East, and Asia to Australia, respectively. It is suggested
      that WTG CP evolution has proceeded along different paths in these three main
      regions, and that WTGs have adapted freely to new hosts in each region. Indeed,
      the virus isolates causing similar diseases of tomato plants in the different
      continents are, with few exceptions, not closely related and warrant recognition
      as separate species.

PMID- 7636486
TI  - Detection of beet necrotic yellow vein virus strains, variants and mixed
      infections by examining single-strand conformation polymorphisms of immunocapture
      RT-PCR products.
AB  - Single-strand conformation polymorphism analysis was found to be a powerful tool
      for rapidly assigning large numbers of beet necrotic yellow vein virus (BNYVV)
      isolates to a known strain group as well as for detecting mixed infections, minor
      variants or new strain groups. The prevalence of the B-type in Germany and France
      and the A-type in most other countries was confirmed. Minor variants with a very
      restricted distribution were detected occasionally. New rhizomania outbreaks in
      Great Britain were caused either by the A- or B-type or mixtures of both
      suggesting introduction of BNYVV from several sites abroad. An entirely different
      BNYVV type (P-type) was identified in a small area in France. Evidence for
      further strain groups in China was also obtained.

PMID- 7636487
TI  - Analysis of potato virus X coat protein genes in relation to resistance conferred
      by the genes Nx, Nb and Rx1 of potato.
AB  - The coat protein gene nucleotide sequences from eight previously uncharacterized
      strains of potato virus X (PVX) were determined. Comparison of the deduced amino
      acid sequences showed that two classes of PVX coat protein, designated types X
      and B, could be distinguished based on protein length and overall amino acid
      identities. In all there were 14 amino acid positions where all of the type X
      proteins differed from all of the type B proteins. The PVX coat protein is the
      principal viral determinant of the outcome of interactions between the virus and
      potatoes carrying either the Nx or Rx1 resistance genes. The different strains of
      PVX were tested for their ability to overcome resistance conferred by three
      potato resistance genes: Nx, Nb and Rx1. All of the strains that were avirulent
      on potato cultivars carrying the Nx resistance gene were found to have type X
      coat proteins whereas strains capable of overcoming the Nx resistance had type B
      coat proteins.

PMID- 7636488
TI  - Dissemination of wild-type and gC-, gE-and gI-deleted mutants of Aujeszky's
      disease virus in the maxillary nerve and trigeminal ganglion of pigs after
      intranasal inoculation.
AB  - Aujeszky's disease virus (ADV) is a well known neurotropic virus in pigs. In the
      present study the mechanism of spread of ADV along the maxillary nerve and the
      role of the viral envelope glycoproteins gC, gE and gI in this process was
      examined in pigs. The Ka parental strain of ADV and its gC-, gE- and gI-deleted
      mutants were inoculated intranasally in pigs, after which virus dissemination in
      the maxillary nerve and the trigeminal ganglion was monitored at time intervals
      by means of virus isolation. The parental strain was isolated from both the nasal
      mucosa and the trigeminal ganglion at 21 h post-inoculation (p.i.), whereas the
      middle part of the connecting maxillary nerve was positive only after 48 h p.i.
      It appears, therefore, that ADV travels from the nasal mucosa via the nerve
      towards the ganglion in a non-infectious form, and then replicates in the
      neuronal somas, after which infectious virus is transported towards the nasal
      mucosa. Although all mutants were present at 48 h p.i. in the nasal mucosa and
      the trigeminal ganglion, the appearance of infectious virus in the maxillary
      nerve was clearly delayed with gE- and gI- mutants. It is suggested that
      glycoproteins gE and gI are involved in the axonal transport of infectious ADV
      away from neuronal cell bodies, also called anterograde transport.

PMID- 7636489
TI  - Insect densoviruses may be widespread in mosquito cell lines.
AB  - A diagnostic PCR assay was designed based on conserved regions of previously
      sequenced densovirus genomic DNA isolated from mosquitoes. Application of this
      assay to different insect cell lines resulted in a number of cases of consistent
      positive amplification of the predicted size fragment. Positive PCR results were
      subsequently confirmed to correlate with densovirus infection by both electron
      microscopy and indirect fluorescent antibody test. In each case the nucleotide
      sequence of the amplified PCR fragments showed high identity to previously
      reported densoviruses isolated from mosquitoes. Phylogenetic analysis based on
      these sequences showed that two of these isolates were examples of new
      densoviruses. These viruses could infect and replicate in mosquitoes when
      administered orally or parenterally and these infections were largely avirulent.
      In one virus/mosquito combination vertical transmission to progeny was observed.
      The frequency with which these viruses were detected would suggest that they may
      be quite common in insect cell lines.

PMID- 7636490
TI  - Ultrastructure of human astrovirus serotype 2.
AB  - The ultrastructure of human astrovirus serotype 2 (H-Ast2) grown in cell culture
      was analysed by electron microscopy of thin sections and negatively stained
      preparation. Infected LLCMK2 cells, as visualized in thin sections, contained
      cytoplasmic aggregates of dense or hollow-cored particles that aggregated in
      quasicrystalline arrays and were specifically labelled using a rabbit polyclonal
      anti-Ast2 antiserum. H-Ast2 particles from the supernatant of infected LLCMK2
      cells in thin sections after flat- embedding were similar in size to
      intracellular virions. In negatively stained preparations, these virus particles
      had an external diameter of 41 nm and exhibited a well defined layer of surface
      spikes. Pentagonal and hexagonal contours were occasionally visible, and probably
      correspond to the projections of icosahedral structures. Star-like morphologies
      and particles with surface triangular hollows were seen in dark areas of the
      preparations only after a short treatment of the viruses of pH 10. Incubation of
      the viruses at pH 10.5 induced a rapid disassembly of the virus particles. The
      finding that the particles with icosahedral geometry and surface spikes are fully
      infective allows an alternative morphological model to the traditional one for
      astroviruses to be proposed.

PMID- 7636491
TI  - Elongation activity of poliovirus RNA polymerase derived from Sabin type 1
      sequence is not temperature sensitive.
AB  - Determinants of attenuation in the Sabin type 1 strain of poliovirus are located
      in the 5' noncoding region, the capsid coding region and the viral RNA-dependent
      RNA polymerase (3Dpol) coding region. These mutations also contribute to a
      temperature sensitive pheno-type of virus replication. We have cloned and
      expressed the Sabin 1 virus 3Dpol) protein which contains three amino acid
      differences from the wild-type (Mahoney) sequence, as well as a wild- type
      polymerase containing only a single Sabin amino acid substitution at nt 6203.
      These enzymes have been examined and compared for temperature sensitive
      polymerase activity. Wild-type and mutated polymerases demonstrated identical
      specific activities at 30, 35 and 39 degrees C. All three showed the same
      kinetics of heat inactivation after pre-incubation at elevated temperatures. Thus
      the contribution of Sabin 3Dpol sequences to the inability of the virus to grow
      at elevated temperatures must lie in a function or activity of the enzyme other
      than RNA polymerization. A likely reaction is the initiation step of RNA chain
      synthesis.

PMID- 7636492
TI  - Moesin, and not the murine functional homologue (Crry/p65) of human membrane
      cofactor protein (CD46), is involved in the entry of measles virus (strain
      Edmonston) into susceptible murine cell lines.
AB  - Membrane cofactor protein (CD46) has been firmly established as the major high
      affinity receptor for measles virus (MV). In addition, another protein, moesin,
      has been shown to be linked with the susceptibility of human cells to MV
      infection. Murine cells are largely resistant to MV infection, although a number
      of cell types can be productively infected. As murine cells do not express CD46
      an additional mechanism for the uptake of MV is likely. Murine cells possess a
      functional homologue of CD46 (Crry/p65) in addition to murine moesin, which has
      nucleotide and amino acid homology to human moesin. We report that anti-moesin
      monoclonal antibodies 119 and 38/87 reduce the number of infectious centres
      attributed to MV in murine cell lines NS20Y and L929, whereas polyclonal antisera
      specific for Crry/p65 and CD46 had no effect on MV infection of these cells. We
      suggest that moesin may be important in the non-CD46-mediated uptake of MV strain
      Edmonston by susceptible murine cell lines.

PMID- 7636493
TI  - Characterization of the small open reading frame on genome segment A of
      infectious pancreatic necrosis virus.
AB  - The genome of infectious pancreatic necrosis virus (IPNV) is composed of two
      segments of dsRNA. The larger segment contains a small ORF partly overlapping the
      5' end of the polyprotein reading frame. Yet very little is known about this
      possible new gene, which presumably codes for a 17 kDa polypeptide (VP5). The
      region of the viral genome which encompasses the small ORF was reverse
      transcribed and amplified by PCR before cloning and sequencing. Analysis of the
      sequences obtained from five different virus strains revealed that the small ORF
      is not found on one of them, and that it is truncated on two others. Moreover,
      the deduced amino acid sequences did not appear to be well conserved. Despite the
      large variations between IPNV strains at the genomic level, all predicted VP5 are
      arginine-rich basic polypeptides. To verify whether the small ORF is translated
      into protein in fish cells, the 17 kDa polypeptide of the VR-299 strain was
      expressed as fusion protein in a prokaryotic expression vector and used to
      produce a specific antiserum. This antiserum reacted with concentrated virus in
      an immunodot assay indicating that VP5 is synthesized in infected cells, but
      probably only in small quantities. When tested with 12 other IPNV strains,
      results were less conclusive than those obtained with strain VR-299.
      Nevertheless, three of the 12 viruses gave a clearly negative signal in the
      immunodot assay, suggesting that possibly more than one viral strain lacks the
      small ORF.

PMID- 7636494
TI  - Different allelic effects of the codons 136 and 171 of the prion protein gene in
      sheep with natural scrapie.
AB  - Scrapie is a transmissible degenerative disease of the central nervous system
      occurring naturally in sheep. It belongs to the group of prion diseases also
      affecting man in which an abnormal isoform of the host-encoded prion protein
      (PrP) accumulating in the brain is responsible for neuronal death. Three main
      polymorphisms have been described in the sheep PrP gene, at positions 136, 154
      and 171. A strong association between susceptibility/resistance to natural
      scrapie and a dimorphism at codon 136 of the ovine PrP gene has been reported in
      several breeds, including Romanov. This dimorphism, however, is not found in all
      scrapie-affected breeds. We have compared the PrP genotypes of Lacaune sheep
      obtained from enzootically affected flocks with those of apparently healthy
      sheep. A third variant at codon 171 was also evidenced. The results were compared
      with those obtained in a single experimental Romanov flock orally challenged with
      nematode parasites in which scrapie suddenly appeared and killed 80% of the
      sheep. We present evidence that, even in different epizootological circumstances,
      the major genetic factor controlling the susceptibility/resistance to natural
      scrapie in sheep, is represented by codon 171 genotype of the PrP gene. We also
      suggest that a modification of the allelic effects of codon 136 can occur in
      heavily infected animals.

PMID- 7636496
TI  - Loss of serum HCV RNA at week 4 of interferon-alpha therapy is associated with
      more favorable long-term response in patients with chronic hepatitis C.
AB  - To determine the virological factors associated with a favorable long-term
      response to interferon-alpha (IFN) therapy in chronic hepatitis C virus (HCV)
      infection, 61 Japanese patients with chronic HCV infection were treated with IFN
      for 24 weeks (780 million units in total) and followed for 8 to 16 months after
      cessation of therapy. Ten patients dropped out because of severe side effects. Of
      the 51 patients who completed IFN therapy, 23 showed complete and sustained
      response (CR --> SR), 13 complete response with early relapse (CR --> Rel), and
      15 no response to IFN (NR). For the pretreatment serum HCV RNA level, 20/23 who
      had CR --> SR had < 10(6) eq/ml compared to 3/13 CR --> Rel and 1/15 NR (P <
      0.01). Serologically defined HCV type 2 infection was also associated with a
      better opportunity to develop CR --> SR compared to CR --> Rel of NR (P < 0.01).
      Loss of serum HCV RNA at week 4 of IFN therapy was also associated with a more
      favorable long-term response [17/19 CR --> SR were HCV RNA negative compared to
      3/11 CR --> Rel (P < 0.01) and 2/13 NR (P < 0.01)]. In contrast, normalization of
      serum alanine aminotransferase (ALT) levels at week 4 was found in 9/19 CR --> SR
      compared to 8/11 CR --> Rel (P = NS), and 0/13 in NR (P < 0.01). Six months after
      cessation of IFN therapy, 3/25 CR --> SR patients were HCV RNA positive despite
      normalization of serum ALT levels. These data indicated that in addition to
      pretreatment serum HCV RNA levels and HCV type, the kinetics of response to IFN
      (at week 4) were also predictive of subsequent long-term response to IFN in
      patients with chronic HCV infection.

PMID- 7636495
TI  - Persistent B19 parvovirus infections in haemophilic HIV-1 infected patients.
AB  - B19 infection can be acquired by transmission with blood factors in patients with
      congenital bleeding disorders, requiring clotting factor concentrates. In
      immunodeficient patients, the failure of immunity to clear B19 virus may produce
      persistent infections. The presence of B19 DNA in blood samples from seven
      haemophilic patients with concomitant HIV-1 infection was studied over a period
      of three-to-four years. Dot blot hybridization assays with DNA and RNA probes
      were used to detect medium high viremias, and polymerase chain reaction (PCR) to
      detect very low viremic titres. Three patients were negative for B19 DNA in all
      the blood samples, while four patients were persistently positive for B19 DNA.
      Viral persistence, which in one patient was detected throughout the study period
      (40 months), occurred at low titre in all four positive patients with some
      recurrent increases in viral titre. In the four patients persistently positive
      for B19 DNA, acute or chronic clinical symptoms and signs that could be
      associated with B19 were not noted when virus was present at low titre (B19 DNA
      detectable only by PCR). When patients had a higher viral titre (B19 DNA
      detectable by dot blot hybridization) acute manifestations (aplastic crisis,
      Fifth disease, fevers, pneumonitis) were found.

PMID- 7636497
TI  - Peripheral lymphocytes of clinically non-progressor patients harbor inactive and
      uninducible HIV proviruses.
AB  - The HIV viral burden and RNA expression in a selected group of infected,
      clinically non-progressor patients were investigated. Five fast-progressor
      patients and 10 AIDS cases were included as controls. The HIV viral load was
      investigated by semiquantitative polymerase chain reaction (PCR) in adherent
      macrophages and in genomic and extragenomic fractions of lymphocytes. HIV DNA was
      not found in macrophages in the non-progressor subjects, was weakly positive in 2
      of 5 fast-progressors and strongly positive in most of the AIDS patients. The
      number of HIV proviruses found in lymphocytes of the non-progressor subjects
      varied from 5 to 160 copies/microgram DNA, values ten times lower than those
      recorded in fast-progressors and AIDS patients. The extragenomic HIV DNA (2 LTR
      forms) was absent or barely detectable in the lymphocytes from non-progressors
      and abundant in the other groups. HIV RNA was not found in the lymphocytes of all
      non-progressors. This may indicate that a latent state of HIV provirus exists in
      the lymphocytes of these subjects. To investigate this point, cultivation and
      stimulation with PHA (phytohemoagglutinin) and PMA (phorbol 12-myristate 13
      acetate) of lymphocytes from these subjects were attempted but after 6 days HIV
      RNA (RT-PCR for gag region) was still absent or barely detectable in these
      patients. There are no other reports of the absence of HIV provirus induction in
      lymphocytes from infected individuals. If confirmed in a larger number of
      patients, such non-inducibility might serve as a predictor marker of progression
      of the disease.

PMID- 7636498
TI  - Heterosexual activity as a risk factor for the transmission of hepatitis C virus.
AB  - Hepatitis C virus (HCV), the major causative agent of non-A, non-B hepatitis, is
      transmitted by parenteral exposure. Transmission by sexual activity, however, is
      controversial. Possible behavioral risk factors for HCV infection were studied
      retrospectively among imprisoned men (n = 201, mean age: 45 years [S.D. 13]) who
      visited a health service center at a Japanese correctional facility for medical
      examination. Seropositivity of anti-HCV antibody was disproportionately high
      (49.8%) in comparison with volunteer blood donors. Among possible risk factors
      significant on univariate analysis, intravenous drug abuse and Tama-Ire, a
      Japanese custom of sexual behavior that suggests frequent, aggressive or
      promiscuous heterosexual activity, proved to be independent risk factors for HCV
      infection (odds ratio = 7.39, 95% CI = 3.41 - 16.05, P < 0.0001; odds ratio =
      3.16, 95% CI = 1.16 - 8.64, P = 0.026, respectively) as shown by logistic
      regression analysis. The data suggest that HCV may be transmitted by sexual
      activity.

PMID- 7636499
TI  - Polymerase chain reaction for rapid detection of ocular adenovirus infection.
AB  - Adenoviruses are associated with endemic and epidemic acute conjunctivitis, large
      nosocomial outbreaks reflecting virus transmission on unwashed hands or
      inadequately sterilised ophthalmic instruments. The polymerase chain reaction
      (PCR) proved more sensitive than antigen detection by immune dot-blot test for
      the rapid diagnosis of ocular adenovirus infection (sensitivities in a
      retrospective study 112/123 (91%) versus 72/123 (59%), P < 0.001). Indeed, in a
      prospective comparison, DNA amplification and virus isolation generated similar
      numbers of positive results (34 versus 32), though five PCR positive results were
      possibly false positives. The sensitivity of the PCR was largely independent of
      adenovirus subgenus or serotype, though reduced sensitivity with subgenus B
      strains could not be excluded. Specimen preparation for DNA amplification using a
      simple lysis buffer proved more effective than phenol-chloroform extraction. The
      immune dot-blot test gave unavoidable false positive results, but with the PCR
      this problem could be minimized by technical modifications. The PCR could replace
      antigen detection and virus isolation as the initial test for adenoviruses in
      conjunctival swabs, with cell culture only being retained for adenovirus
      serotyping in PCR positive specimens and for other viruses such as herpes
      simplex.

PMID- 7636500
TI  - UV-inactivated measles virus stimulates human and mice naive lymphocytes to
      proliferate in vitro.
AB  - Ultra violet (UV) light-inactivated measles virus was used for the lymphocyte
      proliferation assay, where it caused consistently adult human peripheral blood
      monolymphocytes (PBML) proliferation which was not dependent on the measles virus
      complement fixation titre in the donor's sera. When the cord blood lymphocytes
      from newborn baby and spleen lymphocytes from unprimed Balb/c, C57bl and CBA mice
      were used in the proliferation assay, all the lymphocytes were stimulated by the
      UV-inactivated measles virus in a dose-dependent manner. These results suggest
      that: (1) lymphotropic measles virus can also activate lymphocytes in vitro, and
      (2) this activation appeared to be neither species- nor major histocompatibility
      complex (MHC)-restricted. These results may have important implications for
      measles vaccination and the understanding of the immunopathogenesis of measles
      virus infection.

PMID- 7636501
TI  - Quantitative assessment of IgM antibodies towards an immunodominant B-cell
      epitope within the preS2 domain of HBV in the natural course and during combined
      prednisone/interferon alpha 2b treatment of chronic hepatitis B virus infection.
AB  - A direct binding enzyme-linked immunosorbent assay (ELISA) was established for
      quantitative determination of serum IgM antibodies towards a synthetic peptide
      corresponding to a selected segment (14-21) of the preS2-gene product containing
      an immunodominant linear B-cell epitope. The prevalence of IgM anti-preS2 (14-21)
      antibody titers > 1,000 for hepatitis B e antigen (HBeAg)-positive patients with
      chronic hepatitis B virus (HBV) infection was 38% (22/58) and 10% (2/21) for
      HBeAg-negative subjects (P < 0.005). IgM anti-preS2 (14-21) reactivity was
      detected during the clinical course of chronic HBV infection and IgM anti-peptide
      antibody titers declined and disappeared before spontaneous HBe/anti-HBe
      seroconversion. Recombinant interferon (IFN)-alpha 2b with an antecedent short
      course of corticosteroids was administered to eight Chinese patients with chronic
      HBV infection. The IgM anti-preS2 (14-21) reactivity was monitored consecutively
      during treatment and patients were followed for more than 1 year. A close
      association between the presence of pretreatment IgM anti-preS2 (14-21) in serum
      and the capacity to respond favorably to the combined prednisone/IFN-alpha 2b
      therapy was detected. The IgM anti-preS2 (14-21) titers decreased during
      treatment with subsequent loss of detectable antibodies 8-16 weeks after the
      initiation of therapy. This decrease was concomitant with an alanine
      aminotransferase (ALT) augmentation preceding the disappearance of HBV-DNA and
      anti-HBe seroconversion. Long-term remission was not observed in treated patients
      who lacked detectable levels of pretreatment IgM anti-preS2 (14-21) in the
      circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7636502
TI  - Varicella-zoster virus assembly protein p32/p36 is present in DNA-containing as
      well as immature capsids.
AB  - Varicella-zoster virus (VZV) produces a group of nucleocapsid proteins (the
      p32/p36 nucleoprotein complex) which are the VZV analogues of the herpes simplex
      virus type 1 (HSV-1) and cytomegalovirus (CMV) assembly proteins. There are
      multiple components in the VZV p32/p36 complex, with major proteins of 32 and 36
      kDa and minor proteins of 34 and 38 kDa. In HSV-1 the assembly proteins have been
      shown to be present in immature (B) capsids, but are removed prior to the
      formation of mature (C) capsids containing the viral DNA genome. Our work has
      shown that VZV produces capsids corresponding to the B and C forms. However, in
      contrast to HSV-1, VZV also produces "B/C" capsids that appear to contain both
      the assembly proteins and the viral DNA genome. Possible mechanisms for this are
      discussed. In addition, it was shown that VZV capsids appear to lack the 36 and
      38 kDa proteins, and based on this observation we suggest that these may
      represent unprocessed forms of the assembly protein. In both HSV and CMV, a much
      larger, cross-reactive protein has been identified as the full-length product of
      the gene coding for the assembly protein. The homologous VZV gene (ORF 33)
      theoretically has the capacity to produce a 66 kDa protein. However, no such
      protein is readily apparent in VZV-infected cells. The presence of an
      immunoreactive 64 kDa protein was demonstrated in purified VZV capsids which may
      represent the full-length ORF 33 protein.

PMID- 7636503
TI  - Sequence comparison of echovirus type 30 isolates to other enteroviruses in the
      5'noncoding region.
AB  - The genetic relationship between echovirus type 30 (E30) isolates were
      characterised by means of amplification of a part of the 5'noncoding region by
      polymerase chain reaction and direct sequencing. Later, the E30 sequences were
      compared with other enteroviruses. Homology between recent clinical E30 isolates
      from different years exceeds 98% at the nucleotide level. Comparing the E30
      sequence with other enteroviruses, homology varied between 68% (coxsackievirus
      A24) and 93% (coxsackievirus B3). E30 appeared to have coxsackie B-like
      characteristics in this genomic part. It is considered that E30 and coxsackie B
      viruses belong to the same enterovirus subgroup.

PMID- 7636504
TI  - Hepatitis E virus infection in hemophiliacs.
AB  - Israel is endemic for hepatitis E virus (HEV), the causative agent of enteric non
      A, non-B hepatitis. Transmission is via the feco-oral route but the possibility
      of transmission through blood transfusion has been raised. This question was
      addressed by examining sera from 188 hemophilic patients in Israel, screening was
      performed with an enzyme immunoassay (EIA) for antibody against hepatitis E virus
      (anti-HEV) and confirmed with a neutralization test. Sixteen patients (9%) were
      seropositive for anti-HEV. A statistically significant difference was not found
      between the seroprevalence in this group and that of a healthy Israeli control
      population, matched for sex and age. The anti-HEV-seropositive hemophiliacs had
      the same seroprevalence of antibodies to hepatitis B and C virus and to HIV and
      the same number of cases with chronic hepatitis as among the anti-HEV
      seronegative patients. The seroprevalence of antibodies to hepatitis A virus
      (anti-HAV) was, on the other hand, higher in the anti-HEV-seropositive group.
      This study indicates that HEV is not transmitted by cryoprecipitate or
      lyophilized factor concentrates. High prevalence of coinfection with hepatitis A
      supports our conclusion that HEV infection in Israeli hemophiliacs was due mainly
      to feco-oral transmission.

PMID- 7636505
TI  - Mutations of some critical amino acid residues in the hepatitis B virus surface
      antigen.
AB  - Amino acid substitutions at several positions in the surface antigen (HBsAg) of
      hepatitis B virus (HBV) in natural isolates and the products of recombinant DNA
      molecules have identified important residues for cross-reaction with specific
      antibodies (anti-HBs) and the induction of antibodies with certain serological
      specificities. In a further group of mutants described here, cysteine residues in
      a region believed to be significant of the a epitope have been changed to
      serines. Of the three adjacent cysteine residues at positions 137, 138 and 139,
      mutation of either of the flanking residues reduced cross-reactivity with
      polyclonal anti-HBs, while alteration of the central residue was relatively well
      tolerated. Mutation of cysteine 149 to serine or of glycine 145 to arginine
      (imitating naturally occurring mutants), lysine, or glutamatic acid all led to
      loss of cross-reactivity with polyclonal antisera.

PMID- 7636506
TI  - Usefulness of simple assays for serum concentration of hepatitis C virus RNA and
      HCV genotype in predicting the response of patients with chronic hepatitis C to
      interferon alpha 2a therapy.
AB  - The use of two new assays was evaluated for predicting the response to interferon
      (IFN) therapy in patients with chronic hepatitis C. The genotype of hepatitis C
      virus (HCV) was established by an enzyme-linked immunosorbent assay based on
      genotype-specific recombinant peptides of the NS4 region (genotyping ELISA). The
      concentration of HCV RNA was measured by a branched DNA assay (bDNA assay).
      Seventy-eight patients received the same regimen of IFN alpha 2a. Of the 74
      patients assessed who completed the program, 38 (51.4%) were responders; i.e.,
      their serum aminotransferase levels remained normal for 6 months or longer after
      stopping IFN, while 36 (48.6%) were nonresponders. The results of the HCV
      genotype determined by the genotyping ELISA and by the polymerase chain reaction
      (PCR) assay based on genotype-specific primers were similar. The serum
      concentrations of HCV RNA as measured by the bDNA assay and by the competitive
      PCR assay correlated closely and significantly (r = 0.82, P < 0.001). Multiple
      logistic regression analysis showed that the serum concentration of HCV RNA
      determined by the bDNA assay, the HCV genotype determined by the genotyping
      ELISA, and the histology activity index (HAI) of the liver were independently
      associated with IFN efficacy. By using these three variables in combination, a
      predictive rate of 82.4% was obtained. A lower level of HCV RNA, genotype 2 and a
      lower HAI score for liver histology were predictive of a favorable response to
      IFN. Thus, the genotyping ELSIA and the bDNA assay appear to be useful for
      clinical management of patients receiving IFN therapy.

PMID- 7636507
TI  - Sequential respiratory syncytial virus and cytomegalovirus pneumonia following
      bone marrow transplantation.
AB  - A 6-month-old child with familial hemophagocytic lymphohistiocytosis (FHL)
      experienced early sequential pneumonia due to respiratory syncytial virus (RSV)
      and cytomegalovirus (CMV) following bone marrow transplantation (BMT). The
      patient was deficient in natural killer (NK) cell activity (as found frequently
      in patients with FHL), and this risk factor may have played a major role in the
      concomitant infection by the two viral pathogens. Rapid diagnostic methods for
      both viruses are essential and early specific treatment may serve to ameliorate
      RSV- and CMV-induced lung injury in these life-threatening infections.

PMID- 7636508
TI  - Distribution of varicella-zoster virus gpI and gpII and corresponding genome
      sequences in the skin.
AB  - In the course of varicella-zoster virus (VZV) infection, some viral capsid
      antigens are found in the epidermis and dermis. The aim of this study was to
      investigate the localisation of two major VZV glycoproteins (gpI and gpII) and of
      their respective genes in the skin. The distribution of VZV gpI and II in 27
      formalin fixed paraffin embedded skin biopsies from herpes zoster eruptions were
      compared by immunohistochemistry. Double immunostaining was carried our to
      identify infected cells. The presence of viral nucleic acids coding for gpI and
      gpII was examined by in situ hybridisation. The distribution of gpI and gpII and
      their corresponding genome sequences was similar in the epidermis. gpI and gpII
      were also detected in dermal FXIIIa positive dendrocytes, in Mac 387 and CD68
      positive macrophages, and in perineural and endothelial cells. However, the
      corresponding viral nucleic acids were rarely and barely detected in these cells
      of the dermis. It is concluded that VZV infection of epithelial cells follows a
      different course than in dermal cells.

PMID- 7636509
TI  - HPV prevalence in cytomorphologically normal cervical scrapes of pregnant women
      as determined by PCR: the age-related pattern.
AB  - Diverging data exist on human papillomavirus (HPV) prevalence in
      cytomorphologically normal scrapes during pregnancy. The prevalence of HPV was
      therefore investigated by polymerase chain reaction method (PCR) in
      cytomorphologically normal scrapes of 709 pregnant women and 3,948 non-pregnant
      women visiting the same hospital during the same time period. The prevalence of
      all types of HPV among pregnant women was 9.6% (68/709) and the high risk HPV
      types of 16 and 18 were found in 3.1% (22/709). In the non-pregnant women the
      prevalence of all types of HPV was 10.9% (432/3,948) with 2.9% (116/3,948) HPV
      types 16 and 18. The highest prevalence of HPV was present in women at younger
      ages in both groups. With increasing age the prevalence declines from about 19%
      (15-25 yrs) to 5% (40-49 yrs). The age-adjusted odds ratio of prevalence of all
      types of HPV in pregnant versus non-pregnant women was 0.73 (95% CI 0.56-0.96, P
      = 0.025) and statistically significant. When HPV types 16 and 18 were considered,
      significant differences were not found. HPV of all types and types 16/18
      prevalence was higher in the second half of pregnancy than in the first part but
      did not reach statistical significance. High HPV copy numbers in the scrapes were
      found during the first half of the pregnancy and not during the second half using
      a semi-quantitative HPV 16/18 PCR detection method. Since the difference in HPV
      prevalence between non-pregnant and pregnant women is very small, it is concluded
      that HPV prevalence in cytomorphologically normal smears is hardly influenced by
      pregnancy.

PMID- 7636510
TI  - Cancer mortality in a residential cohort exposed to environmental selenium
      through drinking water.
AB  - Cancer mortality from 1986 to 1992 was examined in a cohort of 4419 individuals
      who had been residing in an area of the municipality of Reggio Emilia, northern
      Italy, where tap water with unusually high selenium content was accidentally
      supplied. Mortality for all cancers was not significantly different, both in
      males and in females, from that expected using death rates in the remaining
      municipal population as standard rates. No significant difference in mortality
      for site-specific cancers was observed in males, while in females a higher
      mortality for malignancies of the lymphatic-hematopoietic tissue overall
      considered and for non-Hodgkin's lymphoma was detected. Even if evaluation of the
      results is hampered by the low number of cancer deaths on which the analysis is
      based, findings of the study do not support the hypothesis of a strong inverse
      independent relationship between dietary intake of selenium and cancer mortality
      in humans.

PMID- 7636511
TI  - An international collaborative case-control study of severe cutaneous adverse
      reactions (SCAR). Design and methods.
AB  - A multicenter international case-control study has been designed to elucidate the
      etiology of Stevens-Johnson syndrome and toxic epidermal necrolysis (TEN).
      Although these diseases occur rarely, the morbidity is high and the mortality for
      TEN is of the order of 30%. These serious dermatologic conditions have often been
      linked to exposure to drugs. Infective and autoimmune diseases, as well as other
      non-drug risk factors, have also been postulated to be of importance in
      increasing the risk. The design and methods are described, with particular
      attention to the unique challenges for an epidemiologic study of these
      conditions.

PMID- 7636512
TI  - Is the lifetime risk of depression actually increasing?
AB  - Data from an international study of psychological problems in primary care were
      examined for evidence of increasing depression risk. At 15 sites, patients aged
      15-65 (n = 26,421) were screened with the GHQ-12 and a stratified random sample
      (n = 5603) selected for psychiatric assessment (Composite International
      Diagnostic Interview). Initial analyses agreed with earlier cross-sectional
      studies, finding higher depression risk and earlier onset in recent birth
      cohorts. Additional analyses suggested that methods effects may explain these
      findings. First, apparent prevalence increases were nonspecific with similar
      trends seen across all study sites and for all disorders examined. Second,
      reporting patterns suggested significant under-counting of past depressive
      episodes. Respondents of all ages typically reported first onset of depression
      during the last 5 years. Reported lifetime prevalence was only 2.02 times current
      prevalence. These findings suggest that depression risk is not rapidly increasing
      and that true lifetime prevalence is much higher than estimated by cross
      sectional surveys.

PMID- 7636513
TI  - Do reproductive factors influence colorectal cancer survival?
AB  - During 29 years follow up of 63,090 Norwegian women, 1347 women had a diagnosed
      cancer of the colon or rectum. Seven hundred and fifty-five of these women (56%)
      subsequently died of colorectal cancer. We investigated possible relationships
      between reproductive history and cancer survival and found little evidence that
      reproductive history is of prognostic value for colorectal cancer survival.

PMID- 7636514
TI  - Methodological issues in assessing reproducibility--a comparative study of
      various indices of reproducibility applied to repeat ELISA serologic tests for
      Lyme disease.
AB  - This study applies and evaluates a variety of different measures of
      reproducibility. As an example, repeat enzyme-linked immunosorbent assays (ELISA)
      for antibodies to Borrelia burgdorferi, the etiologic agent of Lyme disease, are
      used. These repeat tests were part of the 1991 Quality Control Assessment of
      provincial laboratories that was carried out by the Laboratory Centre for Disease
      Control (Ottawa). Twenty-seven sera from cases and non-cases were tested by three
      laboratories, and two laboratories repeated the tests once. Methodological issues
      discussed include: different methods of assessing reproducibility in the
      continuous scale; whether reproducibility should be assessed with data in
      continuous or categorical form; problems assessing the reproducibility of data
      that has been standardized using a calibration-regression line; and problems with
      external generalizability of reproducibility studies of rare diseases. The
      authors conclude that the statistical method used to assess the reproducibility
      of a test must be adjusted to suit individual study designs and data, and the
      usage of the test.

PMID- 7636515
TI  - Recall bias in a case-control study of low birth weight.
AB  - The role of report/recall bias in case-control studies of low birth weight (LBW)
      was investigated in women who gave birth at a tertiary hospital. Prenatal
      exposure information reported at the postpartum interview was compared with that
      documented during pregnancy in obstetric records. 169 cases of LBW and 198
      controls were selected. The two sets of information on case mothers and control
      mothers were compared, using the medical record as a reference. Kappa values were
      estimated. No trend was observed to increase/decrease the sensitivity and
      specificity of recall. Agreement on alcohol use was very low (kappa = 0.11 for
      case mothers and 0.03 for control mothers): on obstetrical records, only 12
      mothers of cases reported habitual alcohol intake at the first prenatal care
      visit, whereas in the interview 69 said yes to the same question; in control
      mothers, the figures were 4 and 89 respectively. Odds ratios (ORs) of exposure
      estimated from the two sets of data did not differ importantly in 8 variables.
      Interview data yielded ORs for hypertension (8.39 versus 4.63), anemia (0.44
      versus 0.99) that were farther from the null, and ORs in the opposite direction
      for alcohol (0.83 versus 1.61) and any drug (0.64 versus 1.42). In conclusion,
      given that OR figures are similar for most variables and no trend is observed in
      sensitivity/specificity, mothers of normal births can be an adequate reference
      group, using personal interviews to obtain information on lifestyle, and medical
      records for conditions.

PMID- 7636516
TI  - Black-white differences in subclinical cardiovascular disease among older adults:
      the Cardiovascular Health Study. CHS Collaborative Research Group.
AB  - Cardiovascular and all-cause mortality are higher in black than white Americans,
      but racial differences in clinical and subclinical cardiovascular disease (CVD)
      have not been examined in older adults. Clinical and subclinical CVD and its risk
      factors were compared in 4926 white and 244 black men and women aged 65 years and
      older. Black participants had lower socioeconomic status and generally higher
      prevalences of CVD and its risk factors, except for adverse lipid profiles.
      Common carotid wall thickness was greater in black than white women, and ankle
      arm blood pressure ratios were lower in black women and men (p < 0.01). After
      adjustment for CVD risk factors, common carotid walls were significantly thicker
      and ankle-arm ratios were lower in blacks than whites of both sexes, while
      internal carotid walls were significantly thinner in black women. Racial
      differences in clinical and subclinical CVD in older adults are similar to those
      reported in younger populations and do not appear to be explained by CVD risk
      factors.

PMID- 7636517
TI  - The prevalence and prophylaxis of gout in England.
AB  - The prevalence of gout in England was reported as having nearly doubled in the
      1970s to about 3 per 1000, and it is possible that it has continued to increase.
      There may also have been some change in the level of prophylactic therapy
      compared with the 44.8% recorded in 1979. In this study, data were provided from
      their morbidity registers by 40 volunteer practices with a combined population of
      over 300,000 patients. Analyses of prevalence by age and sex, and of the extent
      of prophylaxis were made. The male:female ratio and the increase with age found
      were in line with earlier work, but overall prevalence was much higher at almost
      10 per 1000. There was considerable inter-practice variation: 20% of this could
      be accounted for by the age and sex structure of the practice populations, but
      neither economic status nor broad geographical factors appeared to be
      significant, and it did not appear to be due to variation between practices in
      the level of special interest in gout. Prophylactic therapy--almost entirely
      allopurinol--was being prescribed for 48% of the sufferers; though practices
      varied widely in their propensity to give it, as a group the amount of
      allopurinol they used was close to the national average. The increase found in
      the prevalence of gout may be related to an increase in obesity in the
      population.

PMID- 7636518
TI  - A prospective study of the effects of changes in smoking habits on blood count,
      serum lipids and lipoproteins, body weight and blood pressure in occupationally
      active men. The Israeli CORDIS Study.
AB  - In cross-sectional studies, significant differences in cardiovascular disease
      risk factors have been observed between smokers and non-smokers. The aim of this
      study was to examine the effects of smoking initiation and cessation on these
      factors in a population-based prospective study. 987 male employees in Israeli
      industry underwent health screening in the CORDIS study and were re-examined an
      average of two and a half years later. We examined the associations between
      smoking initiation and cessation and changes in blood count, serum lipids and
      lipoproteins, body weight and blood pressure. After adjusting for potential
      confounders, smoking cessation was associated with significant decreases in
      leukocyte count, hemoglobin and hematocrit whereas smoking initiation resulted in
      increased leukocyte count. There were moderate, non-significant increases in both
      serum HDL cholesterol (HDL-C) and LDL-C, and a slight decrease in serum
      triglycerides. Blood pressure remained essentially unchanged, despite the fact
      that smoking cessation resulted in a significant weight increase and smoking
      initiation in a significant decline in weight. These findings demonstrate that
      changes in smoking habits result in fairly rapid changes in blood count and body
      weight, but have much smaller effects on serum lipids and blood pressure.

PMID- 7636520
TI  - Misclassification in a questionnaire survey of varicose veins.
AB  - The objective of this study was to assess the determinants and the effect of
      misclassification in a questionnaire survey of varicose veins. A random sample of
      166 individuals aged 50 years in a larger prevalence study (n = 6874) was
      examined by a surgeon to validate the self-reporting of varicose veins. Varicose
      veins were assessed by a mailed questionnaire completed by the study subjects
      themselves and validated in a clinical examination by a surgeon. The sensitivity,
      specificity, positive and negative predictive values, kappa coefficient, and
      Chamberlain indices of the self-assessed diagnosis in reference to the diagnosis
      by surgeon were estimated overall and in categories of determinants. The overall
      sensitivity and specificity estimates were 0.92 and 0.93, respectively. The
      specificity appeared to be poorer among subjects who reported positive family
      history of varicose veins (0.83) than among those with negative family history
      (0.98). With respect to some other determinants of varicose veins such as gender,
      height and weight, occupational status and position at work, there was at best
      weak but nevertheless inconclusive evidence on possible differential
      misclassification. Sensitivity appeared to be relatively good for epidemiologic
      purposes but one could have hoped for better specificity. The correction for
      misclassification resulted in estimated prevalence of 19% (uncorrected 24%) in
      men and 43% (uncorrected 45%) in women. A questionnaire survey of varicose veins
      showed a relatively good validity. The effect of misclassification in the total 5
      year-old study population was small in women but moderately large in men.
      Familial predisposition to varicosis was associated with a lower accuracy of self
      assessed diagnosis.

PMID- 7636519
TI  - Inter-observer variation in cytological and histological diagnoses of cervical
      neoplasia and its epidemiologic implication.
AB  - Inter-observer variation in cytohistological diagnosis was assessed for 1506
      cervical smears and 883 histological slides from four case-control studies on
      cervical neoplasia. The kappa statistic among a panel of three cytopathologists
      was highest for diagnosis of invasive cancer (0.70 for cytology and 0.74 for
      histology), followed by normal/inflammatory in cytology (0.68) and CIN III in
      histology (0.58). There was also nearly perfect agreement between the final panel
      diagnoses and the original diagnoses made by local cytopathologists, except for
      those of CIN III. Inter-observer variation in diagnosis for CIN III was inversely
      associated with age, number of children (in histology) and sexual activity (in
      cytology). However, the odds ratios for CIN III calculated by each
      cytopathologist's diagnosis were not different from each other for any etiologic
      factor. These results indicate that the diagnoses of invasive cancer and of
      normal/inflammatory changes are highly reproducible and that the inter-observer
      variation does not have much impact on the etiologic risk estimates.

PMID- 7636521
TI  - Fragile environment: cities and crude oil.

PMID- 7636522
TI  - Bacteria no! Fungus yes!

PMID- 7636524
TI  - The predictive value of tumor-cell kinetic parameters in radiotherapy:
      considerations regarding data production and analysis.

PMID- 7636523
TI  - Drug-related fatal anaphylactic shock in Denmark 1968-1990. A study based on
      notifications to the Committee on Adverse Drug Reactions.
AB  - Based on notifications to the Danish Committee on Adverse Drug Reactions and to
      the Central Death Register, 30 cases of fatal drug-induced anaphylactic shock
      were identified during the period 1968-1990. The most frequent causes were
      contrast media for X-ray examinations, antibiotics, and extracts of allergens.
      Nine cases occurred outside hospital; they were mainly caused by the use of
      allergen extracts of moulds for desensitization in general practice. Fatal drug
      induced anaphylactic shock is rare, estimated in the present study at 0.3 case
      per million inhabitants per year.

PMID- 7636525
TI  - Curing cancer in children: minimizing price, maximizing value.

PMID- 7636526
TI  - Paclitaxel plus carboplatin: an effective combination chemotherapy for advanced
      non-small-cell lung cancer or just another Elvis sighting?

PMID- 7636527
TI  - In vivo cell kinetics in head and neck squamous cell carcinomas predicts local
      control and helps guide radiotherapy regimen.
AB  - PURPOSE: To determine whether pretherapy cell kinetics can predict local control
      for patients affected by head and neck squamous cell carcinomas (HN-SCCs) to be
      treated by primary radiotherapy and, moreover, guide to a choice between
      conventional and accelerated radiotherapy. PATIENTS AND METHODS: Between 1989 and
      1993, 83 patients with stage II to IV HN-SCC entered the study. Multiple primary
      tumor biopsies were obtained 6 hours after in vivo infusion of bromodeoxyuridine
      (BrdUrd). In vivo S-phase fraction labeling index (LI), duration of S phase (Ts),
      and potential doubling time (Tpot) were obtained by analysis of multivariate flow
      cytometric data. Between April 1989 and January 1991, 49 patients were treated by
      conventional radiotherapy (70 Gy in 35 fractions over 7 weeks), whereas,
      afterwards, 34 patients entered an accelerated radiotherapy regimen with the
      concomitant boost technique (75 Gy in 40 fractions over 6 weeks). RESULTS:
      Univariate analysis showed that, among patients treated by conventional
      radiotherapy, local control probability was affected by tumor stage (P = .02),
      Tpot (P < .001), and LI (P = .04). Similarly, among patients treated with
      accelerated radiotherapy, we found that local control probability was related to
      tumor stage (P = .03) and primary tumor site (P = .05). For the subgroup of
      patients with tumors characterized by fast growth (Tpot < or = 5 days),
      accelerated radiotherapy gave a better local control rate than conventional
      radiotherapy (P = .02). Cox multivariate analysis of the total number of patients
      showed that the only significant independent prognostic factors related to local
      control were tumor stage (P = .002) and Tpot (P = .004). Moreover, when the Cox
      analysis was restricted to the subgroup of patients treated with conventional
      radiotherapy, Tpot was the most significant factor to predict local outcome (P <
      .01). CONCLUSION: Pretreatment tumor Tpot appears to be an important independent
      prognostic factor for local control of HN-SCC treated by primary radiotherapy.

PMID- 7636528
TI  - Second malignant neoplasms following treatment for Wilm's tumor: a report from
      the National Wilms' Tumor Study Group.
AB  - PURPOSE: The study was undertaken to determine the incidence of second malignant
      neoplasms (SMNs) in patients treated for Wilms' tumor and demonstrate how the
      incidence varied with the initial treatment protocol. PATIENTS AND METHODS:
      Between October 1969 and December 1991, 5,278 assessable patients were enrolled
      onto the National Wilms' Tumor Study (NWTS) and by the end of 1993 had
      contributed 39,461 person-years to a follow-up study. Expected numbers of second
      cancers were calculated by applying national incidence rates to person-years
      classified by age, sex, and calendar year. RESULTS: Forty-three SMNs were
      observed, whereas only 5.1 were expected (standardized incidence ratio [SIR],
      8.4; 95% confidence interval [CI], 6.1 to 11.4). Fifteen years after the Wilms'
      tumor diagnosis, the cumulative incidence of a SMN was 1.6% and increasing
      steadily. Abdominal irradiation received as part of the initial therapy increased
      the risk of a SMN (SIR, 1.43/10 Gy; 95% CI, 1.13 to 1.81). Doxorubicin
      potentiated the radiation effect. Among 234 patients who received doxorubicin and
      greater than 35 Gy of abdominal radiation, eight SMNs were observed, whereas only
      0.22 were expected (SIR, 36; 95% CI, 16 to 72). Treatment for relapse further
      increased the SMN risk by a factor of 4 to 5. CONCLUSION: These results
      demonstrate the importance of current efforts to limit the use of intensive
      chemotherapy and radiation therapy, which are now applied only to patients with
      the most aggressive disease. Continuing close surveillance of the great majority
      of Wilms' tumor patients who become long-term survivors is essential for early
      diagnosis of SMNs and other late sequelae of therapy.

PMID- 7636530
TI  - Concurrent cisplatin/etoposide plus chest radiotherapy followed by surgery for
      stages IIIA (N2) and IIIB non-small-cell lung cancer: mature results of Southwest
      Oncology Group phase II study 8805.
AB  - PURPOSE: To assess the feasibility of concurrent chemotherapy and irradiation
      (chemoRT) followed by surgery in locally advanced non-small-cell lung cancer
      (NSCLC) in a cooperative group setting, and to estimate response, resection
      rates, relapse patterns, and survival for stage subsets IIIA(N2) versus IIIB.
      PATIENTS AND METHODS: Biopsy proof of either positive N2 nodes (IIIAN2) or of N3
      nodes or T4 primary lesions (IIIB) was required. Induction was two cycles of
      cisplatin and etoposide plus concurrent chest RT to 45 Gy. Resection was
      attempted if response or stable disease occurred. A chemoRT boost was given if
      either unresectable disease or positive margins or nodes was found. RESULTS: The
      median follow-up time for 126 eligible patients [75 stage IIIA(N2) and 51 IIIB]
      was 2.4 years. The objective response rate to induction was 59%, and 29% were
      stable. Resectability was 85% for the IIIA(N2) group eligible for surgery and 80%
      for the IIIB group. Reversible grade 4 toxicity occurred in 13% of patients.
      There were 13 treatment-related deaths (10%) and 19 others (15%) died of causes
      not related to toxicity or tumor. Of 65 relapses, 11% were only locoregional and
      61% were only distant. There were 26 brain relapses, of which 19 were the sole
      site or cause of death. There was no survival difference (P = .81) between stage
      IIIA(N2) versus stage IIIB (median survivals, 13 and 17 months; 2-year survival
      rates, 37% and 39%; 3-year survival rates, 27% and 24%). The strongest predictor
      of long-term survival after thoracotomy was absence of tumor in the mediastinal
      nodes at surgery (median survivals, 30 v 10 months; 3-year survival rates, 44% v
      18%; P = .0005). CONCLUSION: This trimodality approach was feasible in this
      Southwest Oncology Group (SWOG) study, with an encouraging 26% 3-year survival
      rate. An Intergroup study is currently being conducted to determine whether
      surgery adds more to the risk or to the benefit of chemoRT.

PMID- 7636529
TI  - Schedule dependency of 21-day oral versus 3-day intravenous etoposide in
      combination with intravenous cisplatin in extensive-stage small-cell lung cancer:
      a randomized phase III study of the Cancer and Leukemia Group B.
AB  - PURPOSE: This was a randomized phase III study to test the schedule dependency of
      etoposide given as a conventional 3-day intravenous (IV) regimen versus a
      prolonged 21-day oral regimen for extensive-stage small-cell lung cancer (SCLC).
      Both regimens contained IV cisplatin. The objectives were to compare survival
      (primary end point) and to establish response rates, failure-free survival, and
      toxicity (secondary end points). PATIENTS AND METHODS: Patients with untreated
      measurable or assessable disease and normal organ function were eligible.
      Randomization was stratified according to performance status 0 versus 1 or 2.
      Treatment consisted of etoposide 130 mg/m2/d IV for 3 days and cisplatin 25
      mg/m2/d IV for 3 days every 21 days for eight courses (schedule 1) versus
      etoposide 50 mg/m2/d orally for 21 days and cisplatin 33 mg/m2/d IV for 3 days
      every 28 days for six courses (schedule 2). In 1990, bioavailability of oral
      etoposide was assumed to be 50%, and the study was designed to deliver the same
      total doses of etoposide and cisplatin on both regimens over 24 weeks without the
      use of growth factors. RESULTS: Between December 1990 and October 1993, 306
      eligible patients were entered. Of these, 69% were male and 66% were > or = 60
      years of age; 21% had a performance status of 0, 47% a performance status of 1,
      and 32% a performance status of 2; 156 were randomized to receive schedule 1 and
      150 to receive schedule 2. Overall median survival estimates were 9.5 and 9.9
      months (difference not significant) for schedule 1 and schedule 2, respectively.
      The 95% confidence interval (CI) for overall survival, 8 to 11 months, was the
      same for both schedules, with 126 and 117 deaths on schedule 1 and 2,
      respectively. Both schedules also resulted in the same median failure-free
      survival estimate of 7 months (95% CI, 6 to 8 months on either schedule).
      Complete and partial responses were observed in 15% and 42% of patients on
      schedule 1 and 14% and 47% on schedule 2, respectively. The overall maximal
      hematologic toxicities grade 3 and 4 for leukocytes, neutrophils, platelets, and
      hemoglobin were, respectively, as follows: schedule 1, 62%, 85%, 32%, and 32%;
      schedule 2, 83%, 83%, 52%, and 53%. Lethal toxicity due to neutropenia and
      infection occurred in 4% of patients on schedule 1 and 10% on schedule 2
      (difference not statistically significant). CONCLUSION: The two schedules of
      etoposide in combination with cisplatin did not result in differences in
      treatment outcome with respect to tumor response and survival. However, a
      significantly greater rate of severe or life-threatening hematologic toxicity was
      noted on the 21-day oral etoposide treatment schedule.

PMID- 7636531
TI  - Expression of p53 oncoprotein in non-small-cell lung cancer: a favorable
      prognostic factor.
AB  - PURPOSE: Mutation of the p53 gene is one of the most common genetic abnormalities
      found in lung cancer. The purpose of this study was to evaluate the prognostic
      value of p53 oncoprotein expression in patients with non-small-cell lung cancer
      (NSCLC). PATIENTS AND METHODS: We studied 156 resected primary NSCLCs by the
      immunohistochemical staining technique, using the p53 antibody DO7. There were 81
      adenocarcinomas, 16 large-cell carcinomas, and 59 squamous cell carcinomas;
      stages were I in 67, II in 30, and III in 59 cases. For each tumor, the
      percentage of p53 positivity was calculated by scoring a minimum of 1,000 cells
      on an arbitrary intensity scale of 0 to 3+. RESULTS: Overall, 103 (66%) tumors
      expressed p53 in more than 0.1% of cells, and squamous cell carcinomas tended to
      express more p53 than adenocarcinomas. Since 50% positivity marked the most
      distinct change in overall survival duration (P = .0008), we divided the cases
      into three groups, as follows: p53-negative (< or = 0.1%, n = 53), low p53 (0.1%
      to 50%, n = 54), and high p53 (> 50%, n = 49). Overall, patients in the high-p53
      group survived longer than those in the low or negative groups, with respective
      median survival durations of more than 65, 26, and 33 months (P = .002). The
      survival difference among the three groups was statistically significant for non
      squamous cell (P = .008), but not for squamous cell (P = .17) carcinomas. Among
      lymph node-negative patients, the survival difference between groups was not
      statistically significant. However, among lymph node-positive patients (n = 78),
      more than 65% of the high-p53 group survived for more than 70 months, while the
      median survival durations for the low and negative groups were 21 and 18 months,
      respectively (P = .001). A Cox regression analysis with multiple covariates
      showed that p53 positivity in more than 50% of tumor cells was an independent
      prognostic factor for better outcome. CONCLUSION: These results suggest that high
      expression of the p53 oncoprotein is a favorable prognostic factor in a subset of
      patients with NSCLC.

PMID- 7636532
TI  - Does knowledge guide practice? Another look at the management of non-small-cell
      lung cancer.
AB  - PURPOSE: To describe Canadian doctors' beliefs about the appropriate role of
      chemotherapy and radiotherapy in the management of non-small-cell lung cancer
      (NSCLC). METHODS: A mail survey of a random sample of Canadian respirologists,
      thoracic surgeons, radiation oncologists, and medical oncologists was performed.
      Three cases of NSCLC were described and respondents were asked to estimate the
      prognosis in each case and to give their treatment recommendations. RESULTS:
      Responses were obtained from 234 of 330 eligible subjects (74%). Doctors'
      treatment recommendations varied widely. After a complete resection for stage II
      NSCLC, 68% recommended no adjuvant treatment, 28% recommended radiotherapy, 1%
      recommended chemotherapy, and 3% recommended both radiotherapy and chemotherapy.
      For an asymptomatic patient with stage IIIb NSCLC, 17% recommended no active
      treatment, 65% recommended radiotherapy alone, 16% recommended radiation and
      chemotherapy, and 2% recommended chemotherapy alone. For an asymptomatic patient
      with a stage IV NSCLC, 80% recommended no active treatment and 20% recommended
      chemotherapy. Doctors' beliefs about the natural history of NSCLC and its
      response to treatment varied widely. Seventy-five percent of respondents believed
      that adjuvant radiotherapy did not increase survival in stage II disease, but 25%
      believed that it did. Thirty percent believed that the addition of chemotherapy
      to radiotherapy in stage III increased survival, but 70% believed that it did
      not. Fifty-five percent believed that chemotherapy increased the median survival
      in stage IV, but 45% believed that it did not. Doctors' beliefs about the
      efficacy of treatment were strongly associated with their treatment
      recommendations. CONCLUSION: Personal beliefs, rather than universal knowledge,
      currently guide the management of NSCLC in Canada.

PMID- 7636533
TI  - Prevention of skin cancer and reduction of keratotic skin lesions during
      acitretin therapy in renal transplant recipients: a double-blind, placebo
      controlled study.
AB  - PURPOSE: The purpose of this study was to investigate the effect of acitretin on
      the development of keratotic skin lesions, and on squamous cell carcinomas and
      basal cell carcinomas in a group of renal transplant recipients. PATIENTS AND
      METHODS: Forty-four renal transplant recipients with more than 10 keratotic skin
      lesions on the hands and forearms were enrolled onto a randomized, double-blind,
      placebo-controlled trial to test the possible skin cancer-preventing effect of a
      6-month treatment with acitretin 30 mg/d. RESULTS: No deterioration in renal
      function occurred in any of the 38 assessable patients treated. During the 6
      month treatment period, two of 19 patients (11%) in the acitretin group reported
      a total of two new squamous cell carcinomas, compared with nine of 19 patients
      (47%) in the placebo group who developed a total of 18 new carcinomas (chi 2 =
      6.27, P = .01). The relative decrease in the number of keratotic skin lesions in
      the acitretin group was 13.4%, as compared with a relative increase in the
      placebo group of 28.2% (difference, 41.6%; 95% confidence interval, 11.5 to
      71.7). Most patients treated with acitretin had mild mucocutaneous side effects,
      but these were easily manageable. Some patients experienced mild hair loss. With
      the exception of three patients, no increase in serum cholesterol or triglyceride
      above pretreatment levels was observed, and liver function remained unchanged in
      all patients. CONCLUSION: Acitretin 30 mg/d over 6 months had significantly more
      effect than placebo in the prevention of squamous cell carcinomas and reduced the
      occurrence of keratotic skin lesions in a group of renal transplant recipients
      with severe lesions. This effect was most pronounced in patients with a history
      of squamous cell carcinomas and basal cell carcinomas.

PMID- 7636534
TI  - Adoptive immunotherapy with tumor-infiltrating lymphocytes and interleukin-2 in
      patients with metastatic malignant melanoma and renal cell carcinoma: a pilot
      study.
AB  - PURPOSE: The objective of this study was to determine the tolerance and effect of
      moderate-dose recombinant human interleukin-2 (rHu IL-2) and tumor-infiltrating
      lymphocytes (TIL) in patients with metastatic melanoma (MM) or renal cell
      carcinoma (RCC) refractory to standard therapy. PATIENTS AND METHODS: Twenty-six
      patients (18 MM and eight RCC) were entered onto this pilot study. TIL were
      isolated from fresh biopsy material and activated with anti-CD3 antibody, OKT3,
      for 48 hours and expanded in 100 IU/mL r-methionyl Hu IL-2 alanine 125 (r-met Hu
      IL-2 [ala-125]). At least 10(10) TIL were reinfused intravenously in three
      divided injections on days 2, 4, and 6 of the protocol. A maximum dose of 30,000
      U/kg of IL-2 per injection was administered every 8 hours from day 2 through day
      11 for a total of 28 doses. RESULTS: Sixteen melanoma patients completed the
      study. Of these, three (19%) showed a durable complete response (CR), nine (56%)
      had no response (NR), and four (25%) had progressive disease (PD). One
      nonresponder demonstrated complete tumor regression within 1 year of treatment.
      Of four assessable RCC patients, two experienced a minor response (MR) and two
      showed NR. All TIL cultures showed comparably high cytotoxic activity as
      determined by antibody-redirected lysis (ARL). More importantly, melanoma TIL
      from responders possessed significantly higher cytotoxicity against autologous
      tumor cells than TIL from nonresponders (P < .05). Production of granulocyte
      macrophage colony-stimulating factor (GM-CSF), interferon gamma (IFN-gamma),
      interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), and IL-4 was
      similar for TIL from melanoma responders and nonresponders, or TIL from RCC
      patients. CONCLUSIONS: Immunotherapy with polyclonally activated TIL and moderate
      dose IL-2 could be successfully used for the treatment of immunogenic tumors with
      less toxicity and lower costs as compared with high-dose IL-2 protocols.

PMID- 7636535
TI  - Interferon alfa-2a and 13-cis-retinoic acid in renal cell carcinoma: antitumor
      activity in a phase II trial and interactions in vitro.
AB  - PURPOSE: A phase II trial of interferon alfa-2a (IFN) and 13-cis-retinoic acid
      (CRA) was conducted in patients with renal cell carcinoma (RCC). In vitro studies
      were performed to investigate potential mechanisms of interaction. PATIENTS AND
      METHODS: Forty-four patients were treated. IFN was given daily at 3 MU and
      escalated to 6 and 9 MU if tolerated. The dose of CRA was 1 mg/kg/d. The effects
      of combining CRA and IFN on the proliferation of five RCC cell lines were
      examined, and retinoid sensitivity was correlated to the expression of retinoic
      acid receptors. RESULTS: Thirteen (30%) of 43 assessable patients achieved a
      major response (three complete and 10 partial). Responding sites included bone
      metastases and renal primary tumors. Seven responding patients remain progression
      free at 10+ to 19+ months. The response proportion was higher than in our prior
      experience with IFN, which was 10% in 149 patients. Eleven of 12 renal cancer
      cell lines were resistant to CRA alone; one, SK-RC-06, showed 90% inhibition of
      cell growth. CRA augmented the antiproliferative effect of IFN in several IFN
      sensitive cell lines, but not in IFN-resistant lines. Northern blot analysis
      showed that expression of retinoic acid receptor-beta (RAR-beta) was repressed
      and not induced by retinoic acid in retinoic acid-insensitive RCC lines. However,
      RAR-beta expression was induced by retinoic acid in SK-RC-06 cells. CONCLUSION:
      IFN and CRA showed antitumor activity in patients with advanced RCC, and the
      proportion and nature of response suggested CRA added therapeutic benefit to IFN.
      A phase III randomized trial of IFN plus CRA versus IFN alone and a phase II
      trial of single-agent CRA have been initiated.

PMID- 7636536
TI  - Phase I/II trial of dexverapamil plus vinblastine for patients with advanced
      renal cell carcinoma.
AB  - PURPOSE: The reduced cardiac toxicity of the dextro-(d-) stereoisomer of
      verapamil (dexverapamil; Knoll Pharmaceuticals, Whippany, NJ) warrants its study
      as a potential multidrug-resistance (MDR) reversal agent. PATIENTS AND METHODS:
      Twenty-three patients with advanced renal cell carcinoma (RCC) were treated with
      vinblastine at a dose of 0.11 mg/kg intravenous (IV) bolus injection on days 1
      and 2 every 21 days. Dexverapamil was added to subsequent cycles after resistance
      had been demonstrated. Dexverapamil treatment was begun 18 hours before day 1 of
      vinblastine administration and was given orally every 6 hours for 12 doses.
      Patients in group A were treated with a dose of 120 mg/m2, and those in group B
      were treated with 180 mg/m2 plus dexamethasone; plasma concentrations achieved in
      patients were correlated with in vitro effects. RESULTS: Toxicities included
      hypotension, asymptomatic bradycardia, and mild atrioventricular conduction
      delays, although one patient had dexverapamil discontinued for grade IV
      congestive heart failure. There were no partial or complete responses. The mean
      day-1 serum dexverapamil plus norverapamil plasma concentrations were 2,575 ng/mL
      (range, 697 to 6,015 ng/mL) for group A and 1,654 ng/mL (range, 710 to 4,132
      ng/mL) for group B at the time of vinblastine administration. These
      concentrations were in the range of those that reversed vinblastine resistance in
      vitro. CONCLUSION: The advantage of dexverapamil as an MDR reversal agent is its
      potential for achieving desired blood levels with substantially less toxicity
      than the racemic mixture of verapamil. Based on tolerability, it is a suitable
      drug for further study in clinical trials of malignancies other than RCC that
      attempt to achieve MDR reversal. The dose of 120 mg/m2 given orally every 6
      hours, with dose escalation based on individual tolerance, represents a feasible
      schedule to be considered for such studies.

PMID- 7636537
TI  - Phase I/II study of intermittent all-trans-retinoic acid, alone and in
      combination with interferon alfa-2a, in patients with epidemic Kaposi's sarcoma.
AB  - PURPOSE: A phase I/II study of oral all-trans-retinoic acid (ATRA; tretinoin),
      administered every other week alone and then in combination with interferon (IFN)
      alfa-2a, was undertaken to evaluate the activity, toxicity, and pharmacokinetics
      of this regimen in patients with human immunodeficiency virus (HIV)-associated
      Kaposi's sarcoma (KS). PATIENTS AND METHODS: Thirteen patients with HIV
      associated KS, eight of whom had more than 100 CD4 cells/microL, were entered.
      The protocol initially called for patients to receive 150 mg/m2/d of ATRA every
      other week. However, this regimen was associated with headaches, and the initial
      dose of ATRA was reduced to 40 mg/m2/d orally in three divided doses, increasing
      to a maximum of 100 mg/m2/d. After 12 weeks, IFN alfa-2a could be added. RESULTS:
      The principal toxicities from ATRA were headaches (12 patients) and dry skin or
      lip (seven patients). Of 12 assessable patients, 10 had progressive disease and
      two had stable disease on ATRA alone. One of eight assessable patients who went
      on to receive ATRA plus IFN alfa-2a had partial response (PR). There were no
      overall changes in the serum HIV p24 antigen (Ag) level or CD4 count during
      treatment with ATRA alone. Peak ATRA levels decreased during the week of
      continuous ATRA therapy, but rebounded when treatment was resumed after a week
      without the drug. CONCLUSION: Intermittent ATRA therapy was reasonably well
      tolerated and provided a means to circumvent the low plasma exposure found with
      continuous ATRA therapy. However, we were unable to document antitumor activity
      in patients with HIV-associated KS.

PMID- 7636538
TI  - Phase I and pharmacologic studies of pyrazoloacridine, a novel DNA intercalating
      agent, on single-dosing and multiple-dosing schedules.
AB  - PURPOSE: To determine the maximum-tolerated doses (MTDs), principal toxicities,
      and pharmacologic behavior of pyrazoloacridine (PZA), a novel DNA intercalator
      with a unique mechanism of action, on single- and multiple-dosing schedules.
      PATIENTS AND METHODS: PZA was administered on a single-dosing schedule as a 1- to
      3-hour infusion and on a multiple-dosing schedule as a 1-hour infusion daily for
      5 days to cancer patients at doses ranging from 400 to 935 mg/m2 and 40 to 180
      mg/m2/d every 3 weeks, respectively. RESULTS: On the single-dosing 1-hour
      schedule, CNS toxicity, characterized by neuropsychiatric and neuromotor effects,
      prompted prolongation of the infusion duration to 3 hours and led to a study of
      PZA on a multiple-dosing schedule. Both measures resulted in lower incidence of
      CNS toxicity. Neutropenia was the principal toxicity and precluded dose
      escalation to levels greater than 750 mg/m2 on the single-dosing (3-hour)
      schedule and 150 mg/m2/d x 5 (total dose, 750 mg/m2) on the multiple-dosing
      schedule. Thrombocytopenia, anemia, and nonhematologic effects occurred less
      frequently. Responses were observed in several patients with platinum- and taxane
      refractory ovarian carcinoma; antitumor activity was also noted in patients with
      cervical and colorectal carcinomas. Significant intraindividual variability
      characterized by the presence of multiple drug peaks and troughs was observed in
      the pharmacologic studies. The maximal PZA concentrations achieved in both
      studies exceeded drug concentrations associated with significant cytotoxicity in
      preclinical studies and correlated with the occurrence of CNS toxicity.
      CONCLUSION: Neutropenia is the dose-limiting toxicity on both schedules and 750
      mg/m2 and 150 mg/m2/d are the recommended starting doses of PZA on single- and
      multiple-dosing schedules, respectively, for minimally pretreated patients in
      phase II studies; slightly lower doses are recommended for more heavily
      pretreated subjects. The favorable toxicity profile of PZA and its antitumor
      activity in several refractory tumors warrant broad phase II evaluations of this
      agent.

PMID- 7636539
TI  - Phase I and pharmacokinetic study of the multidrug resistance modulator
      dexverapamil with EPOCH chemotherapy.
AB  - PURPOSE: Dexverapamil is a competitive inhibitor of the P-glycoprotein (Pgp)
      efflux pump, a potent mechanism of multidrug resistance (mdr-1) in vitro. We
      performed a phase I study to determine the maximum-tolerated dose (MTD) and
      pharmacokinetics of dexverapamil with etoposide, prednisone, vincristine,
      cyclophosphamide, and doxorubicin (EPOCH) chemotherapy. PATIENTS AND METHODS:
      Eligible patients had relapsed or refractory lymphoma or sarcoma. Patients
      initially received EPOCH alone, and those with stable or progressive disease were
      crossed-over to received dexverapamil on subsequent cycles of EPOCH. Dexverapamil
      was administered orally for 6 days and escalated over eight dose levels ranging
      from 240 to 1,200 mg/m2/d. Pharmacokinetics of dexverapamil and its active
      metabolite, nor-dexverapamil, were obtained in most patients. In seven patients,
      pharmacokinetics of doxorubicin, doxorubicinol, and etoposide were determined on
      paired cycles of EPOCH with or without dexverapamil. RESULTS: Sixty-five patients
      received 130 cycles of dexverapamil/EPOCH chemotherapy. The MTD of dexverapamil
      was 150 mg/m2 every 4 hours (900 mg/m2/d), and hypotension was the principal dose
      limiting toxicity. The dexverapamil area under the curve (AUC) increased
      proportionally with dexverapamil dose, but significant interpatient variation
      occurred. At the MTD, the median plasma average concentrations of dexverapamil
      and nor-dexverapamil were 1.2 and 1.4 mumol/L, respectively. Dexverapamil did not
      affect the steady-state concentration (Css) of etoposide, but increased the Css
      of doxorubicin and doxorubicinol nearly twofold. The absolute neutrophil and
      platelet nadirs were significantly lower on the dexverapamil cycles compared with
      cycles of EPOCH alone, but other chemotherapy-related toxicities did not change.
      CONCLUSION: The phase II recommended dose of dexverapamil with EPOCH is 150 mg/m2
      every 4 hours. This dose was well tolerated on an outpatient basis and achieved
      plasma concentrations of dexverapamil and nor-dexverapamil within the effective
      range for Pgp inhibition in vitro. Although dexverapamil increased the
      hematopoietic toxicity of EPOCH, it was mild, readily reversible, and offset by
      EPOCH dose reductions. Dexverapamil should be considered for further study.

PMID- 7636540
TI  - Controlled trial of dexverapamil, a modulator of multidrug resistance, in
      lymphomas refractory to EPOCH chemotherapy.
AB  - PURPOSE: Overexpression of the multidrug resistance gene (mdr-1) is present in up
      to 60% of relapsed lymphomas. To study its role in lymphomas, we conducted a
      controlled trial of dexverapamil, an inhibitor of the mdr-1 gene product, P
      glycoprotein (Pgp), in lymphomas refractory to etoposide, prednisone,
      vincristine, cyclophosphamide, and doxorubicin (EPOCH) chemotherapy. PATIENTS AND
      METHODS: Eligible patients had recurrent Hodgkin's (HD) or non-Hodgkin's
      lymphomas (NHL) and measurable disease. Patients initially received EPOCH alone
      and those with stable tumor over two cycles or progressive disease crossed over
      to receive dexverapamil and EPOCH on subsequent cycles. Dexverapamil was
      escalated eight dose levels, from 240 to 1,200 mg/m2/d. When possible, serial
      biopsies were obtained to measure mdr-1 expression by quantitative polymerase
      chain reaction (PCR). RESULTS: Of 154 patients entered onto the trial, 109 had
      NHL and 45 had HD. The median age was 44 years, 67% had stage IV disease, and the
      median number of prior regimens was two (range, one to 12) in NHL and one (range,
      one to four) in HD. Sixty-four patients (42%) crossed over, of which eight were
      not assessable. The maximum-tolerated dose of dexverapamil was 900 mg/m2/d. Among
      41 NHL patients (excluding mycosis fungoides), there were three complete
      responses (CRs) and two partial responses (PRs) (12%) and five minor responses
      (MRs); two of 10 HD patients achieved PRs. The mdr-1 level was measured in 44
      biopsies from 19 patients. Pretherapy, mdr-1 was low (median, 2.5 U) but
      increased (median, 12.2 U) at crossover. Of six patients with mdr-1 levels
      greater than 15 U, three responded to dexverapamil, while only one of eight
      patients with mdr-1 levels less than 15 U responded. EPOCH and dexverapamil were
      well tolerated, but compared with EPOCH alone, produced more hematologic
      toxicity. CONCLUSION: These results suggest that Pgp plays a role in clinical
      drug resistance of lymphomas. However, they also suggest that mechanisms other
      than Pgp are prominent in heavily pretreated patients and that, although Pgp
      inhibition may be necessary, it is probably insufficient. Earlier intervention
      with dexverapamil may be more effective and warrants further study.

PMID- 7636541
TI  - Etoposide, vinblastine, and doxorubicin: an active regimen for the treatment of
      Hodgkin's disease in relapse following MOPP. Cancer and Leukemia Group B.
AB  - PURPOSE: To evaluate the activity and toxicity of combined etoposide,
      vinblastine, and doxorubicin (EVA) in advanced Hodgkin's disease (HD) in relapse
      from or refractory to mechlorethamine, vincristine, procarbazine, and prednisone
      (MOPP). PATIENTS AND METHODS: Eligible patients were more than 15 years of age
      and had received only one prior course of MOPP and were in relapse with
      measurable disease. The EVA regimen (etoposide 100 mg/m2 intravenously [IV] on
      days 1, 2, and 3; vinblastine 6 mg/m2 IV on day 1; and doxorubicin 50 mg/m2 IV on
      day 1) was administered every 28 days for a minimum of four and a maximum of six
      cycles. Patients were restaged at 3 and 6 months. RESULTS: Forty-five eligible
      patients were treated, with an overall response rate of 73%. There were 40%
      complete responses (CRs) and 33% partial responses (PRs). The median follow-up
      time in 42 months. The median time to treatment failure (TTF) is 10 months, with
      31% continuing progression-free. Eighteen patients achieved a second CR, with
      only seven recurrences in that group. Failure-free survival and overall survival
      were significantly better in patients whose first MOPP-induced remission was
      longer than 12 months and who were free of B symptoms at relapse. Toxicity was
      primarily myelosuppression, which resulted in two toxic deaths. Pulmonary
      toxicity was not observed. CONCLUSION: EVA is an effective second-line regimen
      for the treatment of HD in relapse following MOPP chemotherapy.

PMID- 7636542
TI  - Evaluation of a somatostatin analog in the treatment of lymphoproliferative
      disorders: results of a phase II North Central Cancer Treatment Group trial.
AB  - PURPOSE: Malignant cells from non-Hodgkin's lymphomas (NHL) have been shown to
      express the somatostatin receptor on their cell surface and most NHL are visible
      on somatostatin radioscintigraphy scans. This provided the rationale to conduct a
      phase II trial of a somatostatin analog in patients with B- and T-cell
      lymphoproliferative disorders. PATIENTS AND METHODS: Sixty-one patients with
      measurable or assessable lymphoproliferative disorders (31 stage III or IV low
      grade NHL; 21 chronic lymphocytic leukemia [CLL]; and nine cutaneous T-cell NHL
      [CTCL]) were enrolled. Patients were treated with somatostatin 150 micrograms
      subcutaneously (SQ) every 8 hours for 1 month. Patients with stable or responding
      disease received 2 additional months of therapy; those who responded after 3
      months were treated for an additional > or = 3 months. RESULTS: Sixty patients
      were assessable for toxicity and 56 for response. There were no complete
      remissions. In the low-grade NHL group, 36% (10 of 28 patients; 95% confidence
      interval [CI], 19% to 56%) had a partial remission. Forty-four percent (four of
      nine; 95% CI, 14% to 79%) of patients with CTCL had a partial response. No
      patients with CLL had a partial remission. Among 45 patients with stable disease
      or a partial remission, the mean time to progression (TTP) was 10.9 months
      (median, 6.2; range, 1.6 to 48.5). The drug was well tolerated, with the most
      common side effects being diarrhea and hyperglycemia. CONCLUSION: Somatostatin at
      a dose of 150 micrograms every 8 hours is well tolerated and has activity in low
      grade NHL.

PMID- 7636543
TI  - Second solid malignancies after combined modality therapy for Hodgkin's disease.
AB  - PURPOSE: To determine the actuarial incidence (AI) and relative risk (RR) of
      second solid malignancies (SSM; solid tumors and non-Hodgkin's lymphoma) in
      patients with Hodgkin's disease who were treated with chemotherapy and adjuvant,
      low-dose radiation (combined modality therapy; CMT). PATIENTS AND METHODS: From
      1969 to 1983, 102 patients with previously untreated advanced Hodgkin's disease
      (group A) and 81 patients with recurrent disease after radiation (group B) were
      treated with CMT. Patients were observed for the development of solid tumors (ST)
      and non-Hodgkin's lymphoma (NHL), and the AI and RR were calculated. RESULTS:
      Nearly half of the patients entering remission were observed for greater than 15
      years. At 20 years, the AI for SSM was 12% in group A versus 41% in group B (P =
      .009). The overall RR for developing a ST in group A was 1.88 (not significant)
      versus 8.84 in group B (95% confidence interval, 5.3 to 15.4). The difference in
      the RR between groups A and B was significant (P < .001). The RR for developing
      NHL was significantly increased in both groups, but the difference between groups
      was not significant. CONCLUSION: Previously untreated patients with advanced
      disease who were treated with CMT (group A) had a modest but not significant
      increase in the RR of ST; however, patients treated with CMT for recurrent
      disease (group B) had a highly significant increase in the RR of ST. Possible
      explanations for the increase in ST in group B include more cumulative radiation
      or a greater carcinogenic effect of chemotherapy in previously irradiated
      patients, but it also is possible that the increase is due to a longer follow-up
      time.

PMID- 7636545
TI  - Mass screening and age-specific incidence of neuroblastoma in Saitama Prefecture,
      Japan.
AB  - PURPOSE: To provide the population-based incidence rate of neuroblastoma and to
      determine the effect of mass screening on the annual age-specific incidence of
      the tumor in Saitama Prefecture, Japan, from 1981 to 1992. METHODS: Data on
      screened infants and patients detected by the screening were obtained from the
      records of the Prefectural Screening Center. Data on neuroblastomas in this area
      were obtained from the Children's Cancer Registry of the Saitama Prefectural
      Government (Prefectural Registry) and from the Japan Children's Cancer Registry
      (National Registry). Population data were obtained from the Prefectural Census.
      Mass screening for 6-month-old infants was performed by qualitative assessment of
      urinary vanillylmandelic acid (VMA) from June 1981 to September 1989 and by
      quantitative measurement of VMA/creatinine (Cre) and homovanillic acid (HVA)/Cre
      from October 1989 to December 1992. RESULTS: Between 1981 and 1992, 199 cases of
      neuroblastoma, which include 74 cases detected by mass screening, were identified
      in Saitama Prefecture. The incidence rate for children under 15 years of age
      increased from 6.4/10(6) to 20.1/10(6), that for children 0 to 4 years of age
      increased from 17.0/10(6) to 64.1/10(6), and that for infants under 1 year of age
      increased from 27.9/10(6) to 260.4/10(6) during these 12 years. No significant
      reduction in the incidence rate was observed for children over 1 year of age.
      CONCLUSION: The incidence rate for children under 15 years of age increased with
      mass screening. The rate for infants was sharply increased, with no corresponding
      decrease in the rate for children at older ages. These data suggest that there is
      a subset of neuroblastoma that can be detected by mass screening at 6 months of
      age but would not be diagnosed later clinically.

PMID- 7636544
TI  - B-cell lineage confers a favorable outcome among children and adolescents with
      large-cell lymphoma: a Pediatric Oncology Group study.
AB  - PURPOSE: The goal of this study was to assess the immunophenotype of uniformly
      treated cases of pediatric large-cell non-Hodgkin's lymphoma (NHL) to determine
      the prognostic importance of B-cell and T-cell lineages and of CD30 positivity.
      PATIENTS AND METHODS: Sixty-nine patients were analyzed by immunochemistry. All
      patients were classified histologically, staged in a uniform manner, and treated
      according to one of two protocols for localized (stage I and II) NHL or advanced
      (stage III and IV) large-cell NHL. Antibodies included anti-CD45, CD20, CD45Ra,
      MB-2 (not clustered), CD3, CD45Ro, CD43, CD15, CD30, and CD68. Statistical
      analysis used the exact conditional chi 2 and Kruskall-Wallace tests for clinical
      features and the log-rank test to evaluate event-free survival (EFS). RESULTS:
      Immunophenotypic results demonstrated 25 B-cell, 23 T-cell, and 21 indeterminate
      lineage. Twenty-seven patients expressed CD30 (17 T-cell and 10 indeterminate
      lineage), and of these, 22 showed histology of anaplastic large-cell lymphoma
      (ALCL). B-cell patients were older (P = .018) and showed more favorable survival
      than patients with T-cell or indeterminate lineage (96% EFS at 3 years, 96% v 67%
      and 74%, B v T and indeterminate lineage [P = .027]). B-cell lineage was seen
      more frequently in limited-stage patients, but was also associated with favorable
      survival when stratified for stage (P = .036). CD30 expression (P = .96) and ALCL
      histology (P = .90) did not show significant associations with survival.
      CONCLUSION: We conclude that among pediatric large-cell lymphomas, B-cell lineage
      is proportionately less frequent than in adults and CD30 antigen-expressing
      lymphomas are frequent among patients with T-cell and indeterminate lineage. B
      cell phenotype tends to occur in older children and is associated with superior
      survival.

PMID- 7636546
TI  - Effect of R-verapamil on the pharmacokinetics of paclitaxel in women with breast
      cancer.
AB  - PURPOSE: To study the effect of the multidrug-resistance reversal agent R
      verapamil on the pharmacokinetic behavior of paclitaxel. METHODS: Six women with
      breast cancer who received paclitaxel as a 3-hour infusion with and without R
      verapamil were monitored with frequent plasma sampling up to 24 hours
      postinfusion. Paclitaxel concentrations were measured using a reverse-phase high
      pressure liquid chromatography assay. RESULTS: Concomitant administration of R
      verapamil resulted in a decrease in mean (+/- SD) paclitaxel clearance from 179
      +/- 67 mL/min/m2 to 90 +/- 34 mL/min/m2 (P < .03) and in a twofold increase in
      paclitaxel exposure (area under the curve [AUC]). The mean end-infusion
      paclitaxel concentration was also twofold higher: 5.1 +/- 1.8 mumol/L versus 11.3
      +/- 4.1 mumol/L (P < .03). CONCLUSION: The alteration in paclitaxel
      pharmacokinetics when paclitaxel and R-verapamil are coadministered complicates
      the interpretation of response and toxicity data from clinical trials of this
      drug combination.

PMID- 7636547
TI  - Prognostic factors for prolonged progression-free survival with high-dose
      chemotherapy with autologous stem-cell support for advanced breast cancer.
AB  - PURPOSE: With a median observation time of 50 months from transplant, 13 (22%) of
      62 women with metastatic breast cancer treated with high-dose chemotherapy at the
      Dana-Farber Cancer Institute (DFCI)/Beth Israel Hospital (BIH) remain progression
      free. This study determined factors prognostic for prolonged progression-free
      survival (PFS). METHODS: From June 1988 to January 1992, women who responded to
      standard chemotherapy received high-dose cyclophosphamide, thiotepa, and
      carboplatin with autotransplantation. Data encompassing initial breast cancer
      diagnosis, metastatic presentation, and response to induction treatment were
      examined for correlations with improved PFS. RESULTS: The 5-year PFS rate for the
      entire group is estimated to be 21% (95% confidence interval [CI], 10% to 32%).
      For those patients who attained a complete response (CR) to induction therapy,
      the 5-year PFS rate is estimated to be 31% (95% CI, 0% to 63%). In univariate
      analyses, a single metastatic site, CR to induction therapy, prolonged interval
      from primary diagnosis to first metastases, estrogen receptor (ER)-negative
      tumors, and older age (> or = 40 years) were associated with prolonged PFS. In
      multivariate analyses, single metastatic site (P = .002) and attainment of a CR
      to induction chemotherapy (P = .04) were the most significant predictors for PFS,
      with a strong trend observed for an interval from primary diagnosis to onset of
      metastatic disease of 24+ months (P = .066). CONCLUSION: We and others have shown
      that 10% to 25% of women with metastatic breast cancer are progression-free after
      high-dose chemotherapy with autotransplantation. Those with chemosensitive
      disease, minimal tumor bulk, and a prolonged disease-free interval appear to
      benefit most. Emphasis should continue to focus on the development of more
      effective cytotoxic regimens and biologic approaches to increase the percentage
      of patients who may benefit from this approach.

PMID- 7636548
TI  - Tandem autotransplantation for the treatment of metastatic breast cancer.
AB  - PURPOSE: To investigate the tolerability and impact on progression-free and
      overall survival of two consecutive cycles of high-dose chemotherapy (HDC) with
      autologous bone marrow transplantation (ABMT) in patients with previously
      untreated metastatic breast cancer. PATIENTS AND METHODS: Twenty-eight patients
      received conventional-dose induction therapy (ITx) followed by a planned two
      cycles of HDC with ABMT. Median age was 45 years (range, 34 to 60 years). Sites
      of disease were bone (seven patients), visceral (three), soft tissue (11),
      multiple (six), and CNS (one). The ITx regimens of cyclophosphamide, Adriamycin
      (doxorubicin; Adria Laboratories, Columbus, OH), methotrexate, fluorouracil,
      prednisone, and tamoxifen (CAMFTP) (three patients); fluorouracil, doxorubicin,
      and cyclophosphamide (FAC; 11 patients); cyclophosphamide, methotrexate, and
      fluorouracil (CMF; four patients); or doxorubicin or
      mitoxantrone/cyclophosphamide (10 patients) were given to maximum response (three
      to five cycles). HDC was cyclophosphamide 6 g/m2, carboplatin 2 g/m2, and
      etoposide 625 mg/m2 with ABMT. RESULTS: Of 28 patients, 24 received two (86%)
      cycles of HDC. Four received only one cycle due to persistent toxicity from
      course 1 (one patient), no response to course 1 (two), and death on course 1
      (one). Grade 3 to 4 nonhematologic toxicities included mucositis (in one or both
      cycles in 21 of 28 patients; 75%), diarrhea, nausea, and vomiting. Reversible
      peripheral neuropathy was seen in 15 of 28 patients and was severe in one.
      Documented infections were seen in 19 of 52 cycles. There was one transplant
      related death. Six patients were converted from partial remission (PR) to
      complete remission (CR) with HDC; two of 24 patients (8%) were converted from PR
      to CR with the second cycle of HDC. Progression-free survival rate is nine of 28
      patients (32%) with median follow-up of 23 months (range, 13 to 36+ months).
      Eighteen of 28 patients (64%) have progressed at 1 to 17 months from ABMT.
      CONCLUSION: Two cycles of HDC with ABMT was well tolerated with a high response
      rate in patients with metastatic breast cancer. The importance of the second
      cycle of HDC in this population is unclear.

PMID- 7636549
TI  - Salvage chemotherapy with paclitaxel for recurrent primary brain tumors.
AB  - PURPOSE: To assess the safety and efficacy of Taxol (paclitaxel; Bristol-Myers
      Squibb Co, Princeton, NJ) given at a dose of 175 mg/m2 every 3 weeks as a 3- to 4
      hour outpatient infusion to patients with recurrent malignant primary brain
      tumors who had received prior radiotherapy and at least one chemotherapy regimen
      containing nitrosoureas and who were no longer responding to therapy. PATIENTS
      AND METHODS: Twenty patients (12 men and eight women), ages 19 to 69 years
      (median, 35), with recurrent primary brain tumors were treated according to a
      phase II protocol with intravenous Taxol. Tumor histologies included the
      following: anaplastic astrocytoma (n = 8), glioblastoma multiforme (n = 8), and
      anaplastic oligodendroglioma (n = 4). All patients had been previously treated
      with subtotal resection, limited-field radiotherapy (median dose, 60 Gy; range,
      54 to 78 Gy), and nitrosourea-based chemotherapy. Taxol was administered
      intravenously at a dose of 175 mg/m2/d every 3 weeks with neurologic and
      neuroradiographic evaluation every 8 to 9 weeks. Complete blood cell counts were
      performed weekly. RESULTS: A median of six cycles of Taxol (range, two to 12)
      were administered to 20 assessable patients. Toxicities included partial alopecia
      (n = 10), thrombocytopenia (n = 4), rate of Taxol administration-dependent
      bradycardia (n = 3), and nondisabling peripheral neuropathy (n = 1). No patient
      developed neutropenic fever or sepsis or required cytokine support. Two patients
      required blood-product support (platelet transfusions in both). Four patients
      (20%) demonstrated a partial response (PR) and seven (35%) had stable disease
      (SD) for a total response plus SD rate of 55%. The median time to tumor
      progression was 6 months (range, 2 to 20). CONCLUSION: Taxol demonstrated modest
      efficacy with minimal toxicity in this heavily pretreated cohort of young
      patients with recurrent primary brain tumors.

PMID- 7636550
TI  - Recurrent chiasmatic-hypothalamic glioma treated with oral etoposide.
AB  - PURPOSE: Chiasmatic-hypothalamic gliomas are not amenable to surgical resection
      and therefore are treated with either radiotherapy or chemotherapy. Here we
      report the use of etoposide (VP-16) administered on a chronic oral schedule as a
      novel chemotherapeutic approach. PATIENTS AND METHODS: Fourteen patients, aged 2
      to 15 years, were treated with VP-16 after clinical and neuroradiographic tumor
      progression. Thirteen patients had received prior radiotherapy, and 12 received
      prior nitrosourea-based chemotherapy. VP-16 was administered orally, each cycle
      consisting of 50 mg/m2/d on day 1 through 21 and 36 through 57. Clinical and
      neuroradiographic evaluations were performed during days 58 through 72 before
      initiation of each cycle of therapy. Complete blood counts were performed weekly.
      RESULTS: Treatment-related complications included the following: partial alopecia
      (seven patients); diarrhea (six); weight loss (five); neutropenia (four); and
      thrombocytopenia (four). Three patients required transfusion (three RBC; two
      platelet), and one patient required antibiotic treatment of neutropenic fever.
      There were no treatment-related deaths. Fourteen patients were assessable, five
      of whom demonstrated a radiographic response (one complete and four partial); and
      three patients demonstrated stable disease, with a median duration of response of
      8 months. CONCLUSION: Chronic oral VP-16 is well tolerated, produces modest
      toxicity, and has apparent activity in this small cohort of patients with
      recurrent chiasmatic-hypothalamic gliomas.

PMID- 7636551
TI  - Pretreatment hemoglobin level influences local control and survival of T1-T2
      squamous cell carcinomas of the glottic larynx.
AB  - PURPOSE: A number of reports have documented the relationship between
      pretreatment hemoglobin level and local control and/or survival in the treatment
      of cervix, bladder, and advanced head and neck tumors. Consideration of
      correcting anemia before initiation of radiation therapy may prove increasingly
      important as clinical trials use intensive induction chemotherapy in the
      treatment of head and neck carcinomas. Neoadjuvant chemotherapy may produce
      anemia, which in turn may reduce the effectiveness of subsequent irradiation.
      MATERIALS AND METHODS: One hundred nine patients with T1-2N0 squamous cell
      carcinoma of the glottic larynx were treated with definitive radiotherapy at the
      Fox Chase Cancer Center between June 1980 and November 1990. Follow-up times
      ranged from 26 to 165 months (median, 82). RESULTS: The 2-year local control rate
      for patients who presented with a hemoglobin level < or = 13 g/dL was 66%,
      compared with 95% for patients with a hemoglobin level more than 13 g/dL (P =
      .0018). The 2-year survival rate for patients with a hemoglobin level < or = 13
      g/dL was 46%, compared with 88% for patients with a hemoglobin level more than 13
      g/dL (P < .001). Cox proportional hazards regression analysis showed that
      hemoglobin level (P = .0016) was the only variable that significantly influenced
      local control (P = .0016) and survival (P < .0001). CONCLUSION: Patients who
      presented with hemoglobin levels more than 13 g/dL had significantly higher local
      control and survival rates. The strong apparent correlation between hemoglobin
      level, local control, and survival supports consideration of correcting anemia
      before initiation of radiation therapy.

PMID- 7636552
TI  - Tumor-associated proteolysis and prognosis: new functional risk factors in
      gastric cancer defined by the urokinase-type plasminogen activator system.
AB  - PURPOSE: The significance of tumor-associated proteolysis as reflected by
      parameters of the urokinase-type plasminogen activator (uPA) system for prognosis
      in cancer patients has been proposed because of evidence for its central role in
      basic mechanisms of invasion and metastasis. The aim of the present study was to
      evaluate whether the expression of the uPA parameters might be of clinical value
      in gastric cancer as a tumor/biologically defined risk factor. PATIENTS AND
      METHODS: In a consecutive series of 203 patients resected for primary gastric
      cancer, the expression of uPA, uPA-receptor (uPA-R), plasminogen activator
      inhibitor (PAI)-1, and PAI-2 was determined immunohistochemically. The results
      were classified semiquantitatively (0 to 3). Patients were followed-up
      prospectively for a median of 31 months (range, 9 to 56 months). Disease-free and
      overall survival were analyzed according to Kaplan-Meier and with univariate and
      multivariate Cox analyses in relation to conventional prognostic factors.
      RESULTS: Univariate analyses revealed a highly significant inverse correlation of
      uPA, uPA-R, and PAI-1 expression with survival time (P = .0008, P = .0002, and P
      = .0002, respectively), whereas PAI-2 demonstrated only a weak correlation. In
      multivariate analyses, PAI-1 was an independent and strong prognostic factor (P =
      .005; relative risk, 1.47 per staining degree; 95% confidence interval [CI], 1.31
      to 1.64). In pT1/2 tumors and in Lauren's diffuse and mixed types, uPA, uPA-R,
      and PAI-1 added significant prognostic information. PAI-1 was also associated
      with survival in the subgroup of lymph node-positive patients. CONCLUSION: PAI-1,
      uPA, and uPA-R are new functional risk factors reflecting clinical prognosis. In
      particular, PAI-1 is a new independent variable for the identification of
      patients at high risk after tumor resection. Our results support the hypothesis
      that the uPA system probably is of general importance for prognosis of patients
      with malignant disease, indicating an individual tumor's capacity for invasion
      and metastasis.

PMID- 7636553
TI  - Analysis of a diagnostic strategy for patients with suspected tumors of unknown
      origin.
AB  - PURPOSE: Diagnostic strategies designed to identify the underlying primary
      malignancies in patients with unknown primary tumors (UPTs) have relied on
      retrospective analyses. We analyzed 879 consecutive patients referred with
      suspected UPTs to determine the yield and cost of a limited diagnostic
      evaluation, assess the contribution of specific studies to diagnosis, and analyze
      the survival patterns of patients in whom the primary tumor was diagnosed.
      PATIENTS AND METHODS: Data from patients with a suspected UPT were entered into a
      computerized data base, and the patients underwent a predefined limited
      diagnostic evaluation. Primary malignancies were diagnosed by pathologic review
      alone or by pathologic criteria plus a physical or radiographic finding. Survival
      was measured from diagnosis, estimated using the Kaplan-Meier method, and
      compared using the Cox-Mantel log-rank test. RESULTS: A primary tumor was found
      in 179 of 879 patients (20%). The survival duration of patients in whom the
      primary tumor was diagnosed was superior to that of patients in whom the primary
      tumor remained unknown. Specific patient subsets contributed most to the improved
      survival duration of the group in which the primary tumor was found, including
      lymphoma patients diagnosed solely by pathologic criteria and female patients
      with primary breast or ovarian cancer. The cost of diagnosis was mostly due to
      the extensive use of computed tomography. Except for ovarian cancer, computed
      tomography rarely identified treatable primary tumors. CONCLUSION: The limited
      diagnostic evaluation used in this study identified patients with treatable
      malignancies and increased the survival duration of a population of suspected UPT
      patients. Primary malignancies with the best survival can be diagnosed through
      careful pathologic review and focused evaluations for breast and ovarian cancer
      in women.

PMID- 7636554
TI  - Role of computed tomography in the staging of patients with local-regional
      metastases of melanoma.
AB  - PURPOSE: To determine the value of computed tomographic (CT) scans in the staging
      of asymptomatic melanoma patients who presented with or developed local-regional
      disease as the first site of recurrence and had both a normal chest radiograph
      and serum lactate dehydrogenase (LDH) level. PATIENTS AND METHODS: The records of
      99 patients with local-regional disease were reviewed. Of these, 89 met the study
      criteria and are the subjects of this analysis. Radiologic findings were
      categorized into the following four groups: (1) true-positive (TP), when the scan
      identified either regional or distant disease that was not appreciated on
      physical examination; (2) false-positive (FP), when the scan showed a radiologic
      abnormality that either did not change for at least 6 months or was proven to be
      histologically benign; (3) false-negative (FN), when a patient had symptoms
      suggestive of or suspicious for metastases and was subsequently found to have
      metastases, but all imaging studies were nondiagnostic; and (4) true-negative
      (TN), when all imaging studies were negative for metastases in an asymptomatic
      patient. RESULTS: Findings on CT scan were TP for six patients (7%), FP for 20
      (22%), and TN for 63 (71%). Of the six patients with TP findings, CT of the chest
      identified disease that was not visible on chest radiograph in only one and CT of
      the abdomen or pelvis showed metastases in five. CT or magnetic resonance imaging
      (MRI) of the brain showed no evidence of brain metastases in any patient,
      although it showed asymptomatic skull metastases in one patient. The most common
      FP findings were hypodense hepatic lesions and noncalcified lung nodules.
      CONCLUSION: TP findings are observed in approximately 7% of patients with local
      regional disease, which indicates a low yield but definite usefulness of CT scans
      in this subset of patients. Because FP are more common than TP findings,
      histologic diagnosis of recurrence is advisable. CT scan or MRI of the brain is
      not necessary in asymptomatic patients. CT of the chest adds little to a chest
      radiograph. In light of today's more cost-conscious health-care environment, our
      results are of practical importance.

PMID- 7636555
TI  - Detection of occult melanoma cells in blood with a multiple-marker polymerase
      chain reaction assay.
AB  - PURPOSE: The objective of the study was to develop a sensitive multimarker
      polymerase chain reaction (PCR) assay to detect circulating melanoma cells in
      patient blood. The rationale was that malignant melanoma is heterogeneous in
      regards to antigen expression. PATIENTS AND METHODS: A PCR assay that uses four
      melanoma-associated gene markers (tyrosinase, p97, MUC18, and MAGE-3) was
      developed. Sensitivity and specificity of the PCR assay for individual markers
      were assessed using 10 melanoma cell lines and peripheral-blood lymphocytes (PBL)
      from 39 normal volunteers as controls. The assay's sensitivity and specificity
      were improved using nested primers and Southern blot analysis. Patients (N = 119)
      with American Joint Committee on Cancer (AJCC) stages I to IV disease were
      evaluated for circulating melanoma cells using the four gene markers under
      optimal conditions. RESULTS: All melanoma-associated gene markers were expressed
      in at least 80% of the melanoma lines, whereas 37 of 39 normal PBL tested
      negative for all markers; the remaining two PBL were positive for MUC18. Using
      four markers in the PCR assay was significantly better than using tyrosinase
      alone. There was a significant correlation between the number of positive PCR
      markers, AJCC stage of disease, and progression of disease. In all AJCC stages,
      there were more PCR-positive patients with disease than without disease.
      CONCLUSION: A multimarker PCR assay is more reliable and sensitive than a single
      marker assay for detection of melanoma cells in blood of patients. This assay can
      provide important insight into tumor progression kinetics without major surgical
      or conventional radiologic diagnostic procedures.

PMID- 7636556
TI  - Adjusting the dose of intravenous ondansetron plus dexamethasone to the
      emetogenic potential of the chemotherapy regimen.
AB  - PURPOSE: This pilot, open-label study evaluates the antiemetic efficacy and
      safety of a single 20-mg intravenous (IV) dose of dexamethasone combined with a
      single IV dose of ondansetron (32, 24, or 8 mg) in patients receiving highly
      emetogenic (HE), moderately high emetogenic (MHE), or moderately emetogenic (ME)
      chemotherapy, respectively. PATIENTS AND METHODS: One hundred forty-six patients
      received a single 20-mg IV dose of dexamethasone over 15 minutes beginning 45
      minutes before chemotherapy and either a single 32-, 24-, or 8-mg IV dose of
      ondansetron over 15 minutes beginning 30 minutes before chemotherapy. Patients
      were evaluated for emetic episodes, extent of nausea, and adverse events for 24
      hours after chemotherapy. RESULTS: Complete response (no emetic episodes) was
      noted in 72% (95% confidence interval [CI], 60% to 84%), 88% (95% CI, 79% to
      97%), and 77% (95% CI, 63% to 92%) of patients in the HE, MHE, and ME categories,
      respectively. The proportion of patients who experienced no nausea on the
      posttreatment assessment was 51% (95% CI, 37% to 64%), 69% (95% CI, 56% to 81%),
      and 47% (95% CI, 29% to 65%), respectively. The antiemetic regimens were all well
      tolerated. The proportion of patients with any drug-related adverse events did
      not vary across the three study groups despite the range of ondansetron doses and
      variety of chemotherapy regimens. Mild headache was noted in 28% of patients.
      Other adverse events, all of which were noted in fewer than 10% of patients,
      included lightheadedness, fatigue, dizziness, and constipation. CONCLUSION: A
      single IV dose of either 8, 24, or 32 mg of ondansetron combined with a single 20
      mg IV dose of dexamethasone resulted in good control of acute emesis across a
      wide spectrum of chemotherapy regimens. Nausea control proved somewhat more
      difficult, with approximately 50% of patients in the HE and ME emetogenic
      categories experiencing some degree of nausea. The results of our pilot study
      suggest that adjusting the dose of ondansetron to the intrinsic emetogenicity of
      the chemotherapy regimen permits a more efficient use of ondansetron while
      maintaining good antiemetic control. Such an approach appears worthy of further
      investigation.

PMID- 7636559
TI  - Neoadjuvant chemotherapy in cervix cancer: is it effective?

PMID- 7636558
TI  - Duplicate publication.

PMID- 7636560
TI  - Second malignancy tumors following Hodgkin's disease in children.

PMID- 7636557
TI  - Biology and therapy of pediatric rhabdomyosarcoma.
AB  - PURPOSE: To review key developments in biology and therapy of rhabdomyosarcoma
      (RMS) since the early 1970s. PATIENTS AND METHODS: The literature regarding
      biology, therapy, and late effects of therapy through March 1995 was reviewed.
      RESULTS: The two major histiotypes, embryonal and alveolar, are characterized by
      specific genetic abnormalities that provide clues to mechanisms of tumor
      induction. Alveolar tumors, for example, often possess a chromosomal
      translocation [t(2;13)(q35;q14)] that fuses the PAX3 gene in band 2q35 with the
      FKHR gene in band 13q14, creating a novel chimeric protein that could
      inappropriately activate normal targets of the PAX3 gene product, thereby
      contributing to tumorigenesis. Recognition of prognostically important patient
      groups primarily identified by tumor extent, site, and histology, and development
      of effective risk-based multimodal therapy in randomized trials, have increased
      long-term survival in RMS from 25% in 1970 to more than 70% in current studies.
      The most significant recent gain in therapeutic results was realized in patients
      with gross residual tumor after biopsy. CONCLUSION: Contemporary risk-based
      therapy cures more than two thirds of children with RMS while minimizing acute
      and late effects. Increased dose-intensity of known effective agents with
      hematopoietic growth factor support, new agents, and hyperfractionated
      irradiation are being evaluated in hopes of further improving therapy. Recent
      discovery of novel genetic features in this tumor should lead to better methods
      of diagnosis and risk assessment, and ultimately to identification of molecular
      targets for specific treatment.

PMID- 7636561
TI  - A new enkephalinase inhibitor as an alternative to loperamide in the prevention
      of diarrhea induced by CPT-11.

PMID- 7636563
TI  - Carboplatin dosimetry in renal failure.

PMID- 7636562
TI  - Three-drug combination of cisplatin, dacarbazine, and tamoxifen in metastatic
      malignant melanoma.

PMID- 7636565
TI  - Consultants. An administrator's viewpoint.

PMID- 7636564
TI  - The future of nursing.

PMID- 7636566
TI  - So what good are consultants anyway?

PMID- 7636567
TI  - Personal expenditures, outcomes of care, and a cost accounting model.

PMID- 7636568
TI  - Nursing management in Israel.

PMID- 7636569
TI  - Hospital nurse scheduling.

PMID- 7636571
TI  - Integrating patient care delivery.
AB  - Concepts of coordinated care, case management, and continuous quality improvement
      were applied by a medical center nursing service to improve continuity and
      coordination of patient care between inpatient and outpatient programs. Quality
      and cost outcomes are presented for a pilot project with a total hip replacement
      population.

PMID- 7636570
TI  - Identifying the best in nurse executive leadership: Part 2, Interview results.
AB  - Interview data from four groups of nurse executives further define
      transformational leadership. In Part 1 (June 1995 JONA), the group that received
      the highest staff mean scores were more balanced in their leadership style. The
      second group, which also received high scores in Part 1, were analytic and
      enjoyed moving in to "clean up" situations. In the groups receiving lower scores,
      one relied on common sense in dealing with issues and the other influenced others
      on a situational basis. The author provides further definition on the composition
      of excellent nursing leadership.

PMID- 7636572
TI  - Theory, quality, and economy: a winning combination.
AB  - To meet quality and cost outcomes, a psychiatric hospital used a combination of
      strategies based on leadership and system theories. Leadership approaches
      included credibility, vision, positive self-regard, and communication. Systems
      initiatives included using reinforcing and balancing feedback loops and shifting
      the burden structures. This integration of theory, quality, and economy proved to
      be a winning combination.

PMID- 7636574
TI  - Differentiated nursing practice in all care settings.

PMID- 7636573
TI  - Clinical care coordination program: a working partnership.
AB  - Rural hospitals are burdened by inadequate reimbursement, low occupancy rates,
      high numbers of uninsured patients, and uncompensated care. The authors present
      an innovative solution, the Clinical Care Coordination Program, to uncompensated
      care related to prolonged length of stay in a 188-bed rural hospital. The authors
      discuss the rationale for the development of the program and the steps used to
      develop it. Evaluation of the Clinical Care Coordination Program demonstrated
      statistically significant decrease in length of stay for the services involved in
      the program. Further evaluation of the responses of persons involved in the
      program or affected by it also are positive.

PMID- 7636575
TI  - Telecommuters: the work force of the future.
AB  - Telecommuters are the work force of the future. The dawning of the information
      age, with its explosion of telecommunication technology, presents new
      opportunities for healthcare agencies to extend their borders far beyond
      traditional physical boundaries. The virtual workplace can become a reality and
      position healthcare agencies to be geographically dispersed throughout their
      community. The authors describe a pioneering effort to use telecommunications to
      retain a valuable employee and create a healthcare agency's first virtual
      workplace. Strategies for success in telecommuting also are provided from both
      the telecommuter's and the manager's viewpoints.

PMID- 7636576
TI  - Changing organization structure alone does not change leadership behavior.

PMID- 7636578
TI  - Independent contractor arrangements and IRS audits.
AB  - As government auditors begin their challenges, nurse executives need to review
      their operations to remove any potential audit risks. Although a common practice
      for many institutions, the use of independent contractor arrangements may be
      ruled inappropriate. As a result, many individuals may be reclassified as
      employees, leading to Internal Revenue Service (IRS) assessments of penalties and
      back payroll taxes. It always is prudent to anticipate IRS actions and shore up
      any areas that may lead to tax assessments before they are imposed on the
      institution.

PMID- 7636577
TI  - Ethical dilemmas for nurse administrators.
AB  - Changes in healthcare reimbursement systems have caused nurses in administrative
      practice to focus on ethical issues related to the use of human and financial
      resources. A survey that explored the ethical decisions that arise in nursing
      administrative practices of chief nurse executives in acute-care hospitals is
      reported. Survey findings have implications for nurse administrators dealing with
      resource use issues.

PMID- 7636579
TI  - JONA's Directory of Consultants to Patient Care Administration.

PMID- 7636580
TI  - Shared governance.

PMID- 7636581
TI  - Shared governance: the beacon of hope.

PMID- 7636582
TI  - Pediatric nursing: progress and perspectives.

PMID- 7636583
TI  - Nurse practitioners: myths and misconceptions.

PMID- 7636584
TI  - Nursing education: preparing the nurse of the future.

PMID- 7636585
TI  - Nursing ethics: understanding the moral life.

PMID- 7636586
TI  - The Council on Nursing Research: 25 years of leadership.

PMID- 7636587
TI  - Health care reform: "don't just do something--stand there".

PMID- 7636588
TI  - Cultural diversity: you make a difference.

PMID- 7636589
TI  - Gerontological nursing: successes of the past, visions for the future.

PMID- 7636590
TI  - Hospice nursing: guidance along the "third way".

PMID- 7636591
TI  - Computers in nursing: from the pencil to the PC.

PMID- 7636592
TI  - Alcoholism services: back to the future?

PMID- 7636593
TI  - Nurse-midwifery: a specialty comes of age.

PMID- 7636594
TI  - Homelessness: nursing care for a vulnerable population.

PMID- 7636595
TI  - The Journal: a voice for the nursing profession.

PMID- 7636596
TI  - Community nursing: yesterday, today and tomorrow.

PMID- 7636597
TI  - Psychiatric nursing: trends for clinicians.

PMID- 7636598
TI  - Collective bargaining: empowerment and change.

PMID- 7636599
TI  - Political activism: the individual versus the collective.

PMID- 7636600
TI  - Quality assurance: the foundation of professional care.

PMID- 7636601
TI  - HIV/AIDS: lessons learned from an epidemic.

PMID- 7636602
TI  - Nursing research: influencing public policy.

PMID- 7636603
TI  - Nursing administration: creating evolutionary shifts in leadership.

PMID- 7636604
TI  - Pilot studies in clinical nursing research.
AB  - As clinical nursing research gains prominence in the profession, the need for,
      and advantages of, pilot studies are increasing. This article describes the
      purposes of pilot studies, the potential positive and negative outcomes of these
      studies, and three examples of pilot studies with different outcomes. The
      emphasis is on issues related to clinical nursing research, particularly research
      done in acute care settings.

PMID- 7636605
TI  - Second-year medical students' perceptions of the professional nurse's role.
AB  - This study assesses second-year medical students' views of the nurse and compares
      them to those commonly held by the lay public. Using a modified version of the
      American Nurses Association National Commission's "Nursing Implementation Project
      Survey," views of the role of the registered professional nurse were elicited
      from second-year medical students in 1992 (n = 38), 1993 (n = 50), and 1994 (n =
      70) during workshops designed for them to enhance nurse-physician collegiality.
      Misconceptions about the nursing profession and the scope of the nurse's role to
      ensure positive patient outcomes, were elucidated. Medical students welcomed
      opportunities within the curriculum to redefine their conceptions of the image of
      registered professional nurses. Nurses' advanced professional capabilities and
      interdisciplinary collegiality deserve continued attention throughout the medical
      school curriculum.

PMID- 7636607
TI  - Satisfaction with reduced dentitions in elderly people.
AB  - Natural dentitions of elderly people are often reduced and the remaining teeth
      are heavily restored. It is unknown whether they are satisfied or dissatisfied
      with this situation. To get more insight into this phenomenon 320 dentate non
      institutionalized elderly subjects were clinically examined and interviewed by
      means of a questionnaire. Analysis of the data showed that only 13% of the
      subjects had at least a complete dentition from the right first molar to the left
      first molar; 50% had less than four occlusal units, 39% of the subjects were
      wearing a removable partial denture. Ninety per cent of the subjects was
      satisfied with the dental state and nearly all subjects mentioned they could chew
      well (97%), despite the fact that 91% of the subjects mentioned they had to deal
      with one or more dental discomforts. Satisfaction decreased significantly when
      the number of the occlusal units was reduced or a removable partial denture was
      present. The conclusion is drawn that although the dentitions of the elderly are
      often reduced they are, in general, satisfied with their dental state.

PMID- 7636606
TI  - Critical thinking: the use of intuition in making clinical nursing judgments.
AB  - Making clinical nursing judgements is central to the practice of nursing, and
      critical thinking skills are essential to making clinical judgments. Qualitative
      studies have shown that the use of intuition in making clinical nursing judgments
      is an important part of the critical thinking process. This descriptive
      correlational study examines the relationships between the use of intuition in
      clinical judgment-making and characteristics of the nurse, such as level of
      nursing proficiency and years of clinical experience. Findings support Benner's
      (1984) model of skill acquisition as well as prior findings of studies on the use
      of intuition in clinical nursing practice. Thus, as the level of nursing
      proficiency increases from beginner to expert and as the amount of clinical
      experience increases, the use of intuition to make clinical nursing judgments
      increases significantly.

PMID- 7636608
TI  - Prosthetic possibilities using endosseal implants as anchorages--an
      epidemiological study in 65-year-old subjects.
AB  - In order to evaluate the possibility of using endosseal implants (ITI Dental
      Implant System) and implant-retained prostheses for 65-year-old patients from a
      medium-sized Finnish city, 431 such patients were examined by means of panoramic
      radiographs. The population represents 61% of the total age group in the city
      (born in 1923). The possibility to construct a prosthesis, anchored on implants,
      was evaluated in three different groups. It was shown that in group I (edentulous
      maxilla and mandible, 256 patients) all male and 97% of female subjects could
      have been treated with implant-retained over-dentures in the lower jaw.
      Corresponding figures in the upper jaw were 62% for males and 59% for females. In
      patients with edentulous maxilla and dentulous or partially edentulous mandible
      (group II, 84 subjects) implant-retained overdenture in the maxilla could have
      been possible in 52% of male and 43% of female participants. In subjects with own
      teeth left in both jaws (group III, 91 participants) some kind of implant
      retained bridge or single implants could have been constructed in 70% in maxilla
      and in 92% in mandible.

PMID- 7636609
TI  - Adhesive bonding of titanium with a methacrylate-phosphate primer and self-curing
      adhesive resins.
AB  - The adhesive bonding of titanium was evaluated with the use of a metal primer and
      three types of self-curing luting agent. The primer contained 10
      methacryloyloxydecyl dihydrogen phosphate (MDP). One luting agent was a composite
      material that contained the MDP monomer in its liquid part. The other luting
      agent was based on methyl methacrylate (MMA), initiated with tri-n-butylborane
      derivative (TBB), and contained 4-methacryloxyethyl trimellitate anhydride (4
      META). The MMA-TBB resin without 4-META was used for the control. Pure titanium
      metal specimens were bonded with various combinations. Shear bond strengths were
      determined after repeated thermocycles in water. Both MDP and 4-META were
      effective in bonding titanium. The decrease in bond strength was minimum when the
      titanium was primed with MDP and then bonded with the TBB-initiated resins.

PMID- 7636610
TI  - Symptoms of craniomandibular disorder among elderly people.
AB  - This study investigated the subjective symptoms of craniomandibular disorder and
      the restriction in maximal mandibular opening of 891 elderly Singaporean
      citizens. A distribution of 22% of subjects (20% of the women and 26% of the men)
      reported subjective symptoms of craniomandibular disorders. The most common
      single symptom reported was occasional to frequent clicking sounds from the
      temporomandibular joints (in 15% of subjects). The other single symptoms were
      reported only occasionally in 2-6% of subjects. Nineteen per cent of the subjects
      had some restriction in maximal interincisal opening (30-39 mm) and about 1% of
      subjects were severely restricted in maximal opening (less than 30 mm).
      Subjectively evaluated limitation of wide mandibular opening was recorded for
      only 2% of the subjects. Background factors included general musculo-skeletal
      problems (54%), perceived fair to poor general health (29%), headaches (33%),
      work-related stress (24%), oral parafunctional clenching (4%) and grinding
      activity (4%). This paper confirms earlier reports that the subjective signs and
      symptoms of craniomandibular disorder tend to diminish in elderly people.

PMID- 7636611
TI  - Comparison of methods for measuring surface roughness of ceramic.
AB  - The aim of this investigation was to compare two methods of assessing the surface
      texture of finished dental ceramic; a laser reflectivity method (LSR) and a
      contact stylus tracing method. Identical ceramic blocks (Dicor MGC) were finished
      using a variety of techniques and devices, and the surface texture characterized
      by LSR and contact stylus tracing to enable comparisons to be made between the
      two methods. The results indicate that there is little correlation between the
      two measuring methods. Therefore, laser reflectivity should not be exclusively
      used to measure the surface texture of contoured and finished ceramic materials.
      The development of sophisticated surface characterization parameters suggest that
      the surface characteristics of dental restorations and other related surfaces
      should be described using more than one surface measurement parameter. Surface
      parameters should be chosen which can both quantify surface roughness and provide
      information on the shape of the surface under investigation.

PMID- 7636612
TI  - EMG differences between weak and strong myogenous CMD patients and healthy
      controls.
AB  - Electromyographic and clinical characteristics of 42 myogenous craniomandibular
      disorder (CMD) patients were related to 40 healthy control subjects. Surface EMG
      recordings were obtained from the masseter and the temporal muscles. The clinical
      examination included active maximum mouth opening, endfeel distance, active
      laterotrusion and lateral endfeel distance, dental abrasion, the presence of a
      lateral slide (RCP-ICP) and the amount of static pain. Orthopantomographic X-rays
      were available from 32 CMD patients for measuring the condylar and ramus
      asymmetry. Compared to the control group lower masseter and temporal EMG
      amplitudes were found for myogenous CMD patients (P < 0.001). When the activity
      of the temporal muscle was compared with the activity of the masseter muscle, the
      CMD patients showed proportionally higher temporal muscle activities than the
      controls (P < 0.05, 50% clenching level). CMD patients also showed smaller
      mandibular excursions, larger endfeel distances and more dental abrasion than
      controls. The temporal muscle asymmetries showed significant negative
      correlations with the ramus asymmetries. The lower and upper quartile of the
      distribution of the mean masseter EMG amplitudes were used to distinguish weak
      and strong muscles in patients and controls. Weak patients showed proportionally
      high temporal muscle activities, larger masseter and temporal muscle asymmetries,
      and larger endfeel distances compared to strong CMD patients. These differences
      were not found between weak and strong controls. In conclusion, it can be said
      that the electromyographic and clinical findings of the myogenous CMD patients
      suggest a functional difference between weak and strong patients and indicate the
      need for more individually designed treatment modalities for functional muscle
      and joint CMD problems.

PMID- 7636613
TI  - Presentation of a new Flexi-Flange post system for clinical use.
AB  - Advantages of a new post design, Flexi-Flange are described. It incorporates a
      split-shank parallel threaded post with a flange that seats into an occlusal
      countersunk dentine space. This case report describes placement of three Flexi
      Flange posts in a first bicuspid, canine and central incisor. The Flexi-Flange
      system was designed to offer high retention of the post in the root, superior
      distribution of stresses on insertion and under function, and long-term
      resistance to metal fatigue.

PMID- 7636614
TI  - Temporomandibular joint mobility assessment: a comparison between four methods.
AB  - Temporomandibular joint (TMJ) mobility is assessed in different ways. Measurement
      of the interincisal distance in maximal mouth opening added to the vertical
      overlap of the dentition, i.e. linear mouth opening (LMO); measurement of angular
      displacement of the mandible relative to the cranium at maximal mouth opening,
      i.e. angle of mouth opening (AMO); assessment of the condylar position relative
      to the articular eminence performed on transpharyngeal radiographs in maximal
      mouth opening, i.e. condylar mobility (CM); measurement of angular displacement
      of the mandible at maximal mouth opening relative to the closed mouth position of
      the mandible, assessed on transpharyngeal radiographs in maximally opened and in
      closed mouth position, i.e., radiographic angle of mouth opening (RAMO). To
      compare these TMJ mobility assessment methods and to analyse the relationship
      between LMO, AMO and mandibular length (ML), 28 healthy volunteers (13 females,
      15 males), mean age 29-6 years (range 21-41) with a symmetrical mouth opening
      pattern were assessed. LMO, AMO, ML, and RAMO were measured and CM was assessed
      on transpharyngeal radiographs. LMO and AMO were strongly and significantly
      related (r = 0.71). LMO was significantly influenced by AMO and ML. No
      significant differences between AMO and RAMO were found. CM was strongly and
      significantly related to AMO (r = 0.72) and weakly but significantly related to
      LMO (r = 0.42). Based on the results of this study recommendations are made
      regarding the appropriate application of TMJ mobility assessment methods.

PMID- 7636615
TI  - Development and assessment of an objective method of colour change measurement
      for acrylic denture base resins.
AB  - Current standard specifications for the laboratory evaluation of denture base
      materials require subjective assessment of colour stability. This study evaluates
      a new objective measurement technique for translucent denture base materials, by
      comparing quantitative data with the results obtained from a standard subjective
      method. Preliminary work on three representative commercial acrylic materials
      resulted in the selection of a white background for the quantification of colour
      change of these translucent materials. One half of each sample was exposed to
      artificial sunlight for 24 h. The colour of both exposed and unexposed resin was
      measured on the CIE L*a*b* scale using a photo-electric colorimeter. Significant
      changes in the b* and E* values (P < 0.01) were observed following light
      exposure. Objective data for a wide range of commercial materials were compared
      with the results of a subjective evaluation and it was shown that a change in b*
      of 1.5 units was discernable subjectively by eye for 100% of the cases. It is
      suggested that this method and limit value could form the basis of a new
      objective colour change specification for polymeric dental materials.

PMID- 7636616
TI  - Modelling the effects of enamel anisotropy with the finite element method.
AB  - The finite element method was used to model an in vitro tooth loading system. The
      dentine was modelled as a linear elastic and isotropic material, while the enamel
      was modelled as an anisotropic material to take account of the biological
      variation in prism angulation. The elastic modulus values of enamel and dentine
      used in this analysis were altered in order to replicate the movement of the in
      vitro system. It was found that a dentine modulus of 15 GPa and an enamel modulus
      of 80 GPa in the principal prism direction gave the best replication of cuspal
      movement.

PMID- 7636617
TI  - Activity recognition in long-term electromyograms.
AB  - Long-term electromyography with portable recorders allows the study of muscle
      activity in the natural environment to investigate whether muscle overuse or oral
      habits may contribute to initiate or perpetuate a myoarthropathy of the
      masticatory system. At present, little is known about the behaviour of
      masticatory muscles over long time periods. The aim of this preliminary study was
      to define parameters which allow the automatic recognition of different types of
      oral activities from the electromyogram form. A programme with functional and
      parafunctional activities was performed by four volunteers (total of 333
      functional and 82 parafunctional recordings). Electromyograms of the masseter and
      temporal muscles were recorded by means of a self-developed portable intelligent
      solid state recorder. Signal mean level (mw) and dynamics (dw) within a sliding
      window were determined. Temporal muscle recordings allowed better discrimination
      between function and simulated parafunction. The average of mw for clenching was
      51.4 +/- 3.5% and for tooth grinding 21.2 +/- 2% of the peak electromyogram value
      at maximum voluntary clench. At 0.96 s sliding window duration, clenching, tooth
      grinding and chewing signals had maximum separation, using dw/mw as parameters
      (average: 0.16 +/- 0.01 for clenching, 0.39 +/- 0.01 for teeth grinding and 0.88
      +/- 0.01 for chewing).

PMID- 7636618
TI  - Electromyographic analysis of the sternohyoid muscle and anterior belly of the
      digastric muscle in jaw movements.
AB  - The sternohyoid muscle and the anterior belly of the left digastric muscle were
      studied electromyographically in 20 young adult volunteer individuals. A surface
      monopolar electrode and a needle monopolar electrode, inserted into the muscle
      mass 1.0 cm apart were employed. The most significant action of the two muscles
      was found in the opening of the jaw, during which the sternohyoid muscle
      presented an isotonic contraction, allowing for displacements of the hyoid bone.
      They also acted on those movements that included one of the jaw depression
      components, such as protrusion, lateral movements to either side, and retrusion.
      They were inactive when the jaw was in the resting position. Both muscles
      operated simultaneously most of the time, but a synchronization of their actions
      could not be demonstrated.

PMID- 7636619
TI  - Mullerian inhibiting substance.

PMID- 7636620
TI  - Undergraduate pathology teaching: how good are we? Dr Fox revisited.

PMID- 7636621
TI  - Non-isotopic in situ hybridization at the ultrastructural level.
AB  - Non-isotopic in situ hybridization techniques are becoming increasingly widely
      used at the ultrastructural level, permitting rapid localization of nucleic acid
      targets with a high degree of resolution. Technical considerations dictate that
      the great specificity of the method cannot be matched by a similar degree of
      sensitivity; the value of non-isotopic ultrastructural in situ hybridization lies
      in its unique ability to localize nucleic acid targets in relation to
      submicroscopic cellular structures. This article presents an overview of non
      isotopic ultrastructural hybridization methods and applications.

PMID- 7636622
TI  - Numerical aberrations of chromosomes 1 and 7 in renal cell carcinomas as detected
      by interphase cytogenetics.
AB  - Alcohol-fixed single cell suspensions of 37 renal cell carcinomas (RCCs) were
      assessed by both flow cytometry (FCM) and the fluorescence in situ hybridization
      (FISH) technique, using chromosome 1- and chromosome 7-specific centromere DNA
      probes. DNA diploidy or near-diploidy was observed in 30 of the 37 RCCs and only
      12 of these (near-)diploid tumours were disomic for both chromosomes 1 and 7.
      Numerical aberrations of chromosome 1 and/or chromosome 7 were present in 18 of
      the 30 (near-)diploid RCCs and five of these cases showed monosomy for chromosome
      1 in more than 50 per cent of the tumour cells. A double target FISH, with a
      centromeric and a telomeric specific probe for 1p36, excluded misinterpretation
      on the basis of clustering of 1q12, and suggested a complete loss of chromosome
      1. All these five (near-)diploid RCCs with monosomy for chromosome 1 were
      eosinophilic chromophilic cell carcinomas, according to the Thoenes
      classification of RCC. This observation is of special interest, because it was
      recently concluded from cytogenetic studies that the diagnosis of chromophilic
      renal cell carcinoma must be considered as obsolete. Monosomy for chromosome 1
      seems to be a non-random numerical aberration of (near-)diploid eosinophilic
      chromophilic cell carcinomas, and a gain of one or more chromosomes 1 appeared to
      be a common phenomenon in RCCs, especially in the DNA aneuploid tumours. As these
      chromosomal abnormalities were not found in the earlier classical cytogenetic
      studies, we conclude that in situ hybridization techniques are required in
      addition to chromosome banding techniques to obtain a complete characterization
      of the chromosome imbalances in RCCs.

PMID- 7636623
TI  - Diagnosis of Ewing's sarcoma and related tumours by detection of chromosome 22q12
      translocations using fluorescence in situ hybridization on tumour touch imprints.
AB  - It is increasingly recognized that the identification of t(11;22)(q24;q12) is a
      useful aid in the accurate diagnosis of Ewing's sarcoma and related tumours.
      However, cytogenetic studies have a low success rate and adequate tumour is not
      always available. This study describes the use of fluorescence in situ
      hybridization (FISH) to detect translocations at 22q12, the site of the EWS gene
      involved in t(11;22)(q24;q12), on tumour touch imprints made from true cut core
      needle biopsy and frozen tumour. Of the seven tumours analysed, five diagnosed as
      Ewing's sarcoma or primitive neuroectodermal tumour demonstrated chromosome
      translocation at 22q12. This is a rapid and reliable method to detect a
      diagnostically relevant chromosome translocation using minimal amounts of fresh
      or frozen tumour.

PMID- 7636624
TI  - Distribution of sialosyl Tn and Tn antigens within normal and malignant
      colorectal epithelium.
AB  - Expression of the core blood group structures sialosyl Tn (STn) and Tn is
      regarded as a colorectal cancer-specific change reflecting truncated synthesis of
      the oligosaccharide component of goblet cell mucin. The distribution of STn and
      Tn in normal and malignant epithelium has been studied in detail by a combination
      of mucin-, lectin-, and immunohistochemistry with and without pretreatment with
      potassium hydroxide (KOH), neuraminidase, and KOH-neuraminidase. When O
      acetylated sialic acid (neuraminidase-resistant) is converted by saponification
      to non-O-acetylated sialic acid (neuraminidase-sensitive), normal colorectal
      goblet cells (mainly of the lower two-thirds of crypts) are immunoreactive with
      the monoclonal antibody TKH2 (specific for STn). This immunoreactivity is
      abolished by the interposition of neuraminidase, but goblet cells then become
      immunoreactive with Hb-Tn1 (specific for Tn). While colorectal cancer mucin
      expresses STn, expression of Tn is not seen in either goblet cell mucin or
      extracellular material showing the morphological and histochemical
      characteristics of secretory mucin. Tn expression in cancers is mainly limited to
      the Golgi zone and in a proportion of cases to cytoplasm and apical membrane
      (glycocalyx) of columnar cells and inspissated material within lumina. The
      material reacting with Hb-Tn1 may be upregulated, membrane-associated MUC1
      glycoprotein rather than MUC2 or MUC4 goblet cell mucin. The presence of STn and
      cryptic Tn within normal colorectal goblet cells and the absence of Tn expression
      within colorectal cancer secretory mucin contradicts the generally accepted
      concept of cancer-specific incomplete glycoprotein synthesis within these
      neoplasms.

PMID- 7636625
TI  - Altered expression and function of E-cadherin in cervical intraepithelial
      neoplasia and invasive squamous cell carcinoma.
AB  - HECD-1 monoclonal antibody has been used to localize E-cadherin, a calcium
      dependent cell-cell adhesion molecule, in microwave-treated, paraffin-embedded
      sections from 53 cases of cervical intraepithelial neoplasia (CIN) (11 CIN I, 22
      CIN II, and 20 CIN III), 16 invasive cervical squamous cell carcinomas, and seven
      metastases. In normal cervix, E-cadherin was expressed on the cell membrane of
      basal and parabasal cells. Cytoplasmic staining was present in occasional basal
      cells only. In CIN, the presence and localization of cytoplasmic E-cadherin were
      found to be significantly correlated with the grade of the CIN lesion. In
      squamous cell carcinomas, reduced membranous and increased cytoplasmic staining
      was seen with worsening differentiation. Loss of membranous E-cadherin expression
      was also detected in 4/7 metastatic deposits. E-cadherin expression (120 kD form
      on Western blotting) was seen in human cervical carcinoma cell lines (HT3, ME180,
      C4I, Caski) that maintained the ability to aggregate in a homotypic adhesion
      assay and showed a typical epithelial morphology. E-cadherin-negative cell lines
      (Hela, SiHa, C33A) did not show adhesion. HOG-1 was the only E-cadherin-negative
      cell line which showed a significant degree of cell-cell aggregation. These data
      indicate that loss of membranous E-cadherin expression may represent one of the
      abnormalities underlying loss of cell polarity and differentiation which
      characterize CIN and invasive cervical cancer.

PMID- 7636626
TI  - Parathyroid hormone-related protein antigen localization distinguishes between
      mesothelioma and adenocarcinoma of the lung.
AB  - The distinction between pleural malignant mesothelioma and pulmonary
      adenocarcinoma remains a problem in diagnostic histopathology. Parathyroid
      hormone-related protein (PTHrP) has been demonstrated in the neoplastic cells of
      malignant mesotheliomata, using a polyclonal antiserum raised to synthetic
      PTHrP(1-16). In a series of 44 malignant mesotheliomata and 44 cases of pleural
      adenocarcinomata, PTHrP was localized immunohistochemically in 84 per cent of the
      mesotheliomata and in 11 per cent of the pleural adenocarcinomata. Normal and
      reactive mesothelium did not contain detectable PTHrP. The presence of PTHrP in a
      very high percentage of malignant mesotheliomata indicates the value of including
      it in the panel of antibodies utilized in the differential diagnosis of
      mesothelioma.

PMID- 7636627
TI  - The phenotypic changes in tumour infiltrating lymphocytes and tumour cells
      following intra-arterial infusion of interleukin-2 in patients with squamous cell
      carcinoma.
AB  - This study evaluates the morphological and phenotypic changes that occur in
      squamous cell carcinoma of the head and neck when local infusions of interleukin
      2 (IL-2) are given. Twelve patients were treated with a range of doses of IL-2 (3
      x 10(3) to 3 x 10(6) international units/day) by continuous intra-arterial
      infusion for 10 days. Biopsies of the tumour were taken pre- and 48 h post
      therapy, snap-frozen, cut, and examined histologically and immunocytochemically.
      Local infusions of IL-2 increase the numbers of antigen-presenting Langerhans
      cells (CD1a-positive) and infiltrating lymphocytes, predominantly of the CD3 and
      CD4 (T-helper) phenotypes. Locally infused IL-2 results in the expression of MHC
      (major histocompatibility complex) class II antigens on the surface of the tumour
      cells, capillary and post-capillary endothelial cells, and peri-tumoural
      macrophages. Intratumoural NK (natural killer) cells and CD8-positive (T
      cytotoxic) infiltrating lymphocytes were not increased by this therapy and CD25
      (IL-2 receptor) was only increased in those patients treated at the lower dose
      levels. The system of intra-arterial cytokine infusion into head and neck tumours
      developed in this study is a useful model to examine the biological effects of
      cytokines, since in vivo they are mainly produced and act locally. Furthermore,
      the infused tumours are easily accessible to biopsy. The results from studies
      such as this may influence the design of tumour-targeted cytokine gene therapy
      programmes.

PMID- 7636628
TI  - Platelet-derived endothelial cell growth factor/thymidine phosphorylase
      expression in normal tissues: an immunohistochemical study.
AB  - Angiogenesis is the formation of new blood vessels from the existing vascular
      bed. It is a complex multi-step process controlled by a number of angiogenic
      factors. One such factor is platelet-derived endothelial cell growth factor (PD
      ECGF), recently shown to be thymidine phosphorylase (TP), which is angiogenic in
      several in vivo assays and tumour systems. PD-ECGF/TP catalyses the reversible
      phosphorylation of thymidine to deoxyribose-1-phosphate and thymine. Since PD
      ECGF/TP has an important role in cellular metabolism and in angiogenesis and its
      expression has been only partially characterized, we raised a monoclonal antibody
      against recombinant PD-ECGF/TP and used an immunohistochemical approach to
      examine the expression of PD-ECGF/TP in a comprehensive range of normal human
      tissues. The clone P-GF44.C, which recognizes recombinant PD-ECGF/TP and cell
      lysates transfected with a plasmid expressing PD-ECGF/TP cDNA on Western
      blotting, was selected for its ability to stain routinely processed tissue.
      Staining was observed in both the cytoplasm and/or the nucleus. Immunoreactivity
      was strongly expressed by macrophages, stromal cells, glial cells, and some
      epithelia. Gastrointestinal epithelium, smooth muscle, adrenal, lung, and testis
      were negative. Although endothelial cell expression was observed, there was no
      correlation with sites of new vessel growth. This pattern of expression suggests
      tight PD-ECGF/TP regulation and that cellular thymidine pools may serve to
      control its different functions. Thus, in the nucleus it might modulate the pool
      for DNA synthesis, whilst in the cytoplasm it could control other effects through
      different enzyme systems. The high expression present in macrophages and skin
      might be important for total body thymidine homeostasis.

PMID- 7636629
TI  - Specific accumulation of exogenous fibronectin in experimental
      glomerulosclerosis.
AB  - The prognosis of patients showing glomerulosclerosis as a complication of an
      immunologically mediated kidney disease is poor. To improve the diagnosis and
      treatment of these patients, it is important to understand the processes involved
      in the development of glomerulosclerosis. In this study, we investigated the
      molecular composition of experimental end-stage glomerular sclerotic lesions and
      their pathogenesis in chronic graft-versus-host disease (GvHD) in the mouse and
      chronic serum sickness in the rat. Accumulation studies were performed to
      determine the degree of specific trapping of constituents from the circulation.
      Two different models were investigated to determine whether differences in
      disease initiation resulted in different compositions of the glomerulosclerotic
      lesions. In both models, glomerulosclerosis was preceded by expansion of the
      mesangial matrix and thickening of the glomerular basement membrane (GBM). The
      end-stage sclerotic lesions consisted mainly of fibronectin, which appeared to
      displace the other extracellular matrix (ECM) components peripherally in the
      mesangial matrix and GBM. The abundance of fibronectin in the lesions was not
      reflected in the mRNA levels for this component. Indeed, antibodies directed
      against the cellular form of fibronectin did not stain positive in the end-stage
      lesions. These findings, together with accumulation studies, suggest that
      specific accumulation rather than de novo synthesis of fibronectin plays a major
      role in the development of experimental glomerulosclerosis, which appears to be
      independent of the pathway of induction.

PMID- 7636630
TI  - Microwave antigen retrieval for immunocytochemistry on formalin-fixed, paraffin
      embedded post-mortem CNS tissue.
AB  - Microwave antigen retrieval methods were assessed for a panel of antibodies on
      formalin-fixed, paraffin-embedded sections from a range of human central nervous
      system (CNS) tissues taken at post-mortem. The immunoreactivity of a number of
      antigens (synaptophysin, PGP9.5, GFAP, carbonic anhydrase II, CD68, ferritin, HLA
      DR, alpha beta-crystallin, measles and herpes viruses) was markedly enhanced by
      this procedure compared with other methods of antigen unmasking, such as
      trypsinization. Enhancement was noted both by an increased number of positive
      cells and by the intensity of reactions within individual cells and their
      processes. Furthermore, the microwave method produced uniform immunostaining over
      large surface area sections with no loss of morphological detail. Large cryostat
      sections of CNS tissue can be difficult to obtain with good morphology. The
      ability to retrieve a wide range of antigen in formalin-fixed, paraffin-embedded
      CNS tissue will greatly increase the range of investigations that can be carried
      out on this type of stored material.

PMID- 7636631
TI  - Abolition of endogenous alkaline phosphatase activity by microwave oven heating.

PMID- 7636632
TI  - The specificity of p53 mutation spectra in sunlight induced human cancers.
AB  - Ultraviolet (UV) irradiation emitted by the sun has been clearly implicated as a
      major carcinogen in the formation of skin cancers in man. Indeed, the high levels
      of cutaneous tumors in xeroderma pigmentosum patients (XP) who are deficient in
      repair of UV-induced lesions have confirmed that DNA damage produced by sunlight
      is directly involved in the cancer development. The tumor suppressor gene, p53,
      very frequently found modified in human cancers, has proved to be a perfect
      target gene for correlating mutation spectra with different cancer causing agents
      as there are nearly 300 potential mutation sites available for analysis. In a
      comparative analysis of p53 mutations found in internal cancers with those in
      skin tumours we show here that clear differences exist between the types of
      spectra obtained. The specificity of UV induced mutations in skin cancers is
      confirmed when single and tandem mutations are compared. Most of the p53 point
      mutations found are GC to AT transitions both in skin and internal tumors where
      in the latter they are located mainly at CpG sequences probably due to the
      deamination of the unstable 5-MeC. Moreover, mutations are targeted at py-py
      sequences in over 90% of skin tumors whereas in internal cancers the distribution
      is proportional to the frequency of bipyrimidine sequences in the p53 gene. Most
      significantly, all mutations found in XP skin tumors are targeted at py-py sites
      and more than 50% are tandem CC to TT transitions considered as veritable
      signatures of UV-induced lesions. Tandem mutations are also relatively common
      (14%) in skin tumors from normal individuals compared to their very rare
      occurrence in internal malignancies (0.8%). Finally, nearly all mutations
      observed in XP skin tumors are due to unrepaired lesions remaining on the coding
      strand whereas no strand bias is seen in mutation location of internal or skin
      tumors from normal individuals. In fact the mutation spectrum analysed in XP skin
      cancers has permitted the first demonstration of the existence of preferential
      repair in man. In conclusion, using the p53 gene as a probe it is obvious that
      the mutation spectra from skin tumors are very similar to those observed in UV
      treated gene targets in model systems but statistically different from those
      described in other types of human cancer. This has allowed us to demonstrate,
      without ambiguity, the major role of UV-induced DNA lesions in sunlight related
      skin carcinogenesis.

PMID- 7636633
TI  - Chronic UVB- and all-trans retinoic-acid-induced qualitative and quantitative
      changes in hairless mouse skin.
AB  - Histochemical and ultrastructural studies have already demonstrated that chronic
      exposure to UV radiation induces profound alterations in all structural elements
      of the skin and that topical all-trans retinoic acid (tRA) can substantially
      correct much of the tissue damage. However, previous biochemical studies on
      dermal components of the extracellular matrix have led to contradictory results,
      particularly with regard to the effect of chronic UV exposure. The aim of our
      study was to investigate changes in collagen content and other dermal
      modifications induced by tRA in irradiated and non-irradiated hairless mouse
      skin. Hairless mice were exposed to increasing doses of UVB for 10 weeks (the
      cumulative total dose was 4.6 J cm-2). After the UV irradiation period the
      animals were treated with 0.05% tRA or with ethanol-polyethylene glycol vehicle
      alone three times a week for up to 10 weeks. Non-irradiated animals underwent the
      same treatments. The main clinical and histological changes induced by UVB
      exposure were erythema, wrinkling, keratosis and epidermal thickening. Following
      UVB exposure, tRA treatment did not improve the clinical aspect but increased the
      width of the dermal repair zone. Fibronectin, laminin and type I and VI collagens
      were detected by indirect immunofluorescence techniques in this zone. Type I and
      III collagens were quantitated in skin fragments after cyanogen bromide digestion
      and polyacrylamide gel electrophoresis. Under our experimental conditions, UVB
      irradiation alone induced neither changes in total collagen nor in type I and III
      collagen levels. tRA treatment of irradiated skin significantly increased both
      type I and III collagen levels by factors of 1.33 and 1.88 respectively. The
      ratio of type III to types I + III increased significantly. Topical tRA also
      increased collagen type levels in non-irradiated hairless mouse skin. Type I
      collagen increased proportionally to type III. This study leads to the conclusion
      that topical tRA exerts direct or indirect effects on collagen metabolism in
      irradiated as well as non-irradiated hairless mouse skin.

PMID- 7636634
TI  - Variations in UV radiation in Chile.
AB  - The first observations of UV global radiation in Chile with a portable
      multichannel radiometer are reported. Four UV wavelengths are included: 305, 320,
      340 and 380 nm. Observation latitudes spanning from 18 degrees to 53 degrees S
      allow an estimation of latitudinal variations in daily maxima for both summer and
      winter. Measurements over Santiago deviate from a smooth latitudinal profile,
      probably as a consequence of urban air pollution. The main effect of this is to
      prevent UV solar radiation from reaching the ground, especially during winter.
      Altitudinal increments in UV radiation are estimated by comparing observations
      along the coast and valleys with others on the Andes and one isolated summit.
      Diurnal variations in the height increment support an increase from morning to
      evening. The results indicate that in rural areas the altitudinal increment is
      lower (4%-10% per kilometre) than that reported for Europe, reaching very low
      magnitudes (2% or less) in the Andean summits of desert regions.

PMID- 7636635
TI  - Influence of cell culture medium on the photosensitizing effectiveness of
      bacteriochlorin a.
AB  - To study the photosensitizing properties of bacteriochlorin a (BCA) in a
      (lipo)protein-rich environment, the photosensitizing efficacy was tested by
      clonogenic survival of Chinese hamster ovary and T24 (human bladder carcinoma)
      cells. Confluent cell layers were incubated with 2.5 micrograms ml-1 BCA in cell
      culture medium for 1, 4, 6, 18 and 24 h. Upon illumination with red light it was
      found that BCA was not effective as a photosensitizer in this medium. Extraction
      methods showed that this lack of photosensitization could not be explained by the
      inability of the dye to enter the cells in the presence of cell culture medium.
      The presence of cell culture medium did not change the spectral properties of BCA
      to an appreciable extent. Standard KBr density gradient ultracentrifugation
      showed that in the presence of cell culture medium approximately 20% of the BCA
      was sedimented with low density lipoprotein (LDL) and 60% with high density
      lipoprotein (HDL). Incubating T24 cells 18 h before the clonogenic cell survival
      assay in serum-deficient medium restored the photosensitizing properties of BCA.
      It is proposed that in a protein-rich (in vivo) environment BCA associates with
      lipoproteins and can be taken up by malignant neoplasms via the LDL pathway.

PMID- 7636636
TI  - Correlation between UVA-induced changes in microviscosity, permeability and
      malondialdehyde formation in liposomal membrane.
AB  - The lipid peroxidation, 14C-glucose leakage and microviscosity of liposomal
      membrane increased linearly with increasing UVA fluence. A positive and highly
      significant correlation was found between these properties of the UVA-exposed
      liposomal membrane. The possible involvement of singlet oxygen in the UVA-induced
      damage of liposomal membrane is discussed.

PMID- 7636637
TI  - Intracellular fluorescence behaviour of meso-tetra(4-sulphonatophenyl)porphyrin
      during photodynamic treatment at various growth phases of cultured cells.
AB  - Meso-tetra(4-sulphonatophenyl)porphyrin (TPPS4) taken up by cells is mainly
      localized in lysosomes as previously shown by fluorescence microscopical and
      fluorescence spectroscopical investigations. In the present study the
      intracellular fluorescence behaviour and the intracellular amount of this dye at
      various growth periods of cells were examined. For cells irradiated in the growth
      phase a relocalization of TPPS4 from the lysosomes into the cytoplasm and finally
      into the nucleus was observed. In contrast, for cells irradiated in the
      stationary phase no redistribution could be detected and therefore no evidence
      for severe damage of the lysosomal membranes and subsequently for the release of
      lytical enzymes is given. In both cases lethal damage of the cells was achieved
      as examined using the trypan blue exclusion test. This indicates that damage of
      the lysosomes is less important in the photodynamic inactivation of cells
      sensitized by TPPS4.

PMID- 7636638
TI  - The detection of cyclobutane thymine dimers, (6-4) photolesions and the Dewar
      photoisomers in sections of UV-irradiated human skin using specific antibodies,
      and the demonstration of depth penetration effects.
AB  - Ultraviolet irradiation of skin induces various DNA photolesions. Here we
      demonstrate that irradiation of human buttock skin with 300 nm UVR in situ
      induces thymine dimers and 6-4 photoproducts. Irradiation with 260 nm immediately
      followed by UVA (320 nm) induces the Dewar photoisomers of the 6-4 lesions. All
      three lesions can be detected in methanol-fixed paraffin sections using specific
      monoclonal antibodies. The sections have been analysed in an automated image
      analysis system (Discovery) and the level of immuno-DAB-peroxidase measured in
      individual epidermal cell nuclei as absorption at 460 nm (integrated optical
      density). The staining patterns with the antibodies showed no detectable change
      with epidermal depth by eye after 300 nm irradiation, however, the machine
      detected a fall off with depth of about 2.5% per cell layer. Following
      irradiation with a shorter wavelength (260 nm) there was a rapid fall off in
      staining with depth easily detectable by eye and machine (39% per cell layer).

PMID- 7636639
TI  - New concepts in the treatment of children with acute respiratory distress
      syndrome.
AB  - Recent advances in mechanical ventilation, accompanied with a better
      understanding of the pathophysiology of ARDS, have resulted in a brighter outlook
      for the child who acquires this still dreaded disease. A greater understanding of
      the pathophysiology of ARDS has led to a heightened awareness that the care of
      these patients should be more than just supportive. The potential for
      exacerbation of lung injury by mechanical ventilation is real. Many new therapies
      are being evaluated for the treatment of ARDS; all are intended to reduce
      ventilator-induced injury. With the recognition of "volutrauma" as a serious
      complication of mechanical ventilation in ARDS, the mode of ventilation used
      should minimize the potential for this complication in a child with signs of
      progressive lung disease requiring mechanical ventilation. Optimal integration of
      the many new techniques into the treatment of pediatric ARDS will require more
      research and experience. Surfactant replacement in ARDS as an adjunct to the
      basic care of these patients may be beneficial. Liquid ventilation is another
      exciting new ventilation technique that has a significant protective effect in
      animal models of ARDS. Other therapies, such as tracheal gas insufflation, or
      other new modes of ventilation may also improve outcome. Techniques of high
      frequency ventilation and ECMO in the treatment of children already show
      potential for improved outcome. The decision between using ECMO or
      "nonconventional" forms of mechanical ventilation should be considered carefully,
      after the morbidity of the procedures, the duration of therapy, and the cost have
      been weighed. Centers with experience using ECMO in the setting of pediatric ARDS
      have better results than those where ECMO is infrequently used for this purpose.
      It is imperative that future studies of both mechanical ventilation and ECMO
      describe ventilation strategy and prospectively identify protocols or algorithms
      for ventilator management. Coupled with severity scores, ventilator techniques
      and ECMO can then be systematically compared in children with ARDS.

PMID- 7636640
TI  - Evolving role of theophylline for treatment of chronic childhood asthma.

PMID- 7636641
TI  - Effect of calcium supplementation on blood pressure in children.
AB  - OBJECTIVE: To evaluate the effect of calcium supplementation on blood pressure in
      children. DESIGN: Randomized, double-masked, placebo-controlled trial. SETTING
      AND PARTICIPANTS: One hundred one fifth-grade students in one inner-city school.
      INTERVENTION: Each child consumed 480 ml of juice beverages, containing either no
      calcium or 600 mg calcium (as calcium citrate malate) daily for 12 weeks.
      MEASUREMENTS: At baseline we obtained nutrient data from three sets of 2-day food
      records on each subject. We measured blood pressure four times on each of three
      weekly sittings at baseline and at follow-up. Using multiple linear regression
      analysis, we compared mean blood pressure change in the intervention group with
      that in the placebo group. RESULTS: There were 50 girls and 51 boys; 61 subjects
      were black. At baseline, mean age was 11.0 years, systolic and diastolic blood
      pressures were 101.7 and 57.7 mm Hg, daily total energy intake was 1966 kcal, and
      calcium intake was 827 mg. With control for age, height, hours of television
      watched, and baseline blood pressure, systolic blood pressure increased 1.0 mm Hg
      in the intervention group and 2.8 mm Hg in the placebo group (effect estimate = 
      1.8 mm Hg; 95% confidence interval -4.0, 0.3). In black subjects the intervention
      effect estimate was -2.0 mm Hg (95% confidence interval -4.4, 0.4). From lowest
      to highest quartile of baseline calcium intake (per 1000 kcal), the intervention
      effect estimates were -3.5, -2.8, -1.3, and 0.0 mm Hg (p for trend = 0.009).
      There was little effect on diastolic blood pressure. CONCLUSION: These data
      suggest a blood pressure-lowering effect of calcium supplementation in children,
      especially in subjects with low baseline calcium intake.

PMID- 7636642
TI  - Resting energy expenditure in clinical pediatrics: measured versus prediction
      equations.
AB  - OBJECTIVE: To evaluate the use of resting energy expenditure (REE) prediction
      equations compared with measured REE in children referred for REE to aid clinical
      care. SUBJECTS: One hundred two patients, aged 0.2 to 20.5 years, 55% female,
      with a nutritional diagnosis of failure to thrive (76%), obesity (19%), or other
      (5%). METHODS: We measured REE by indirect calorimetry and compared with
      prediction equations: Food and Agriculture/World Health Organization/United
      Nations University (FAO/WHO/UNU) equation, Harris-Benedict (H-B) equation, and
      two equations from Schofield, one using weight (SCHO-WT) and one using weight and
      height (SCHO-HTWT). RESULTS: The SCHO-HTWT equation more closely predicted
      measured REE (100% +/- 19%), compared with the WHO equation (99% +/- 22%), the
      SCHO-WT equation, (99% +/- 21%), and the H-B equation (92% +/- 25%). The SCHO
      HTWT equation was the best at predicting REE for obese subjects (95% +/- 17%),
      for those with failure to thrive (101% +/- 20%), and for children from birth to 3
      years of age (101% +/- 23%). Nevertheless, the prediction equations closely
      predicted REE in only about 40% of subjects. CONCLUSION: These findings suggest
      that the SCHO-HTWT equation predicts REE in children with clinical nutritional
      problems better than equations that use weight alone. In view of the wide
      variability in REE measurements, however, we believe that REE should be measured
      in patients for whom knowledge of caloric expenditure is required for clinical
      care.

PMID- 7636643
TI  - Zinc supplementation and growth of infants born small for gestational age.
AB  - To analyze the effect of zinc supplementation on postnatal growth of infants born
      small for gestational age, we selected 68 infants at birth and followed them
      monthly for 6 months. They were randomly assigned to a supplemented group (group
      S, n = 35) receiving 3 mg of Zn (acetate) per day, or to a placebo (group P, n =
      33), in a double-blind study. Weight increments in group S were significantly
      higher than those in group P at 2 months (p < 0.003); z scores showed catch-up
      growth only in group S. Length increments were also greater in group S than in
      group P, ending at 6 months were 64.9 +/- 1.8 versus 63.4 +/- 3.5 cm (mean +/-
      SD; p < 0.01); changes in z scores for 6 months were -1.28 to -0.66 in group S
      and -1.43 to -1.47 in group P (p < 0.001). Weight-for-length improved similarly
      in both groups (z score, -2.2 to +0.2). The increase in weight-for-age was higher
      in group S girls (p < 0.034), ending at 6 months with -0.13 +/- 0.59, versus 
      0.52 +/- 0.62 in group S boys, -1.15 +/- 0.49 in group P girls, and -1.05 +/-
      0.80 in group P boys (+/- SD). More infants in group P received cow milk-based
      formula before 4 months because of inadequate weight increments. An additive
      effect on weight increase was observed between Zn supplementation (p < 0.02),
      exclusive breast-feeding after 4 months of age (p < 0.001), and gender (p <
      0.02). Plasma and hair Zn values showed a downward trend, less marked in group S
      than in group P. We conclude that Chilean infants born small for gestational age
      have better weight and linear growth during the first 6 months of life if they
      receive Zn supplementation.

PMID- 7636644
TI  - Intractable diarrhea of infancy with epithelial and basement membrane
      abnormalities.
AB  - We describe a form of intractable diarrhea in six children (four girls) with
      similar clinical histories and identical histopathologic features. The children
      had watery diarrhea of neonatal onset requiring total parenteral nutrition. Two
      had siblings who had died of diarrhea in the first year of life; two others are
      sisters. Repeated duodenal or jejunal biopsies revealed villous atrophy with
      normal or hyperplastic and regenerative cryptae, normal cellularity of the lamina
      mesenterii propria, and no signs of T-cell activation. The main histologic
      features are epithelial dysplasia with focal crowding and disorganization of the
      surface enterocytes, pseudocystic formation of the glands, and abnormal
      regenerative cryptae. The basement membrane components were studied with
      polyclonal antibodies on frozen specimens, and were compared with biopsy
      specimens from patients with celiac disease or autoimmune enteropathy. Relative
      to the control subjects, there was faint and irregular deposition of laminin at
      the epithelium-lamina mesenterii propria interface, whereas deposits of heparan
      sulfate proteoglycan were large and lamellar. The primary or secondary nature of
      these modifications of the basement membrane remains to be determined, but the
      modifications might be related to epithelial abnormalities and to the severity of
      this neonatal diarrhea, which resisted all treatment and necessitated permanent
      total parenteral nutrition.

PMID- 7636645
TI  - Outcome of syndromic paucity of interlobular bile ducts (Alagille syndrome) with
      onset of cholestasis in infancy.
AB  - OBJECTIVE: To determine the outcome, in index patients followed at an American
      Center, of syndromic paucity of interlobular bile ducts (sPILBD; Alagille
      syndrome), with onset of cholestasis in infancy. DESIGN: Cohort. SETTING:
      Regional referral center for infants and children with liver disease. RESULTS:
      During the past 10 years, 26 unrelated children with sPILBD were identified.
      Fifteen (58%) are alive without liver transplantation at a median age of 12.1
      years. Three (11%) died, all before 2 years of age. Eight patients (31%)
      underwent liver transplantation at a median age of 6.5 years; all eight are alive
      a median 5.4 years after transplantation. The most common factors contributing to
      the decision for transplantation were bone fractures, pruritus, and severe
      xanthoma. The predicted probability of reaching 19 years of age without
      transplantation is about 50%; however, with transplantation, the predicted
      probability of long-term survival is 87%. Of 26 patients 4 (15%) have had
      significant central nervous system disease, and two of them have died of
      intracranial hemorrhage. Of the four patients who underwent cholecystoportostomy
      or portoenterostomy, three required liver transplantation. CONCLUSIONS: Children
      with sPILBD identified in infancy because of cholestasis have a 50% probability
      of long-term survival without liver transplantation, a worse prognosis than other
      follow-up studies have reported. In selected patients, liver transplantation
      provides the opportunity for long-term survival with improved quality of life.
      Patients with sPILBD are at risk of having intracranial hemorrhage.

PMID- 7636646
TI  - Anastomotic ulceration: a late complication of ileocolonic anastomosis.
AB  - Symptomatic ulceration developed at a previous ileocolonic anastomosis in six
      children. In the neonatal period all patients had had necrotizing enterocolitis
      that required resection of the terminal ileum, ileocecal valve, and proximal
      portion of the colon. Gross or occult rectal bleeding, with or without pain and
      diarrhea, began 5 1/2 years after successful resection and ileocolonic
      anastomosis. The cause of the ulcers is unknown. They appear inflammatory, both
      grossly and histologically, but have been uniformly unresponsive to
      antiinflammatory medications, antibiotics, and immunosuppressive medication.
      Surgical revision of the anastomosis and ulcer resection in five patients have
      resulted in rapid recurrence in four. Thirteen similar cases have been reported
      in the English-language literature. We conclude that ulceration is a long-term
      complication of neonatal resection of the terminal ileum and ascending colon with
      ileocolonic anastomosis.

PMID- 7636647
TI  - Humoral immunity in DiGeorge syndrome.
AB  - OBJECTIVE: To assess humoral immunity after immunization and natural infection in
      patients with clinical manifestations of the DiGeorge anomalad. DESIGN:
      Retrospective review of cases. SETTING: Ambulatory immunology clinic of a
      tertiary care teaching hospital. PATIENTS: The 13 patients had a symptom complex
      including congenital heart disease, characteristic facies of the DiGeorge
      anomalad, possible hypocalcemia, and thymic hypoplasia or aplasia. Molecular and
      cytogenic studies of 12 patients demonstrated that all had 22q11 microdeletions.
      METHODS: Serial studies included lymphocyte population enumeration by flow
      cytometry, lymphocyte proliferation assays with the mitogens phytohemagglutinin
      and pokeweed mitogen and Staphylococcus aureus, and immunoglobulin quantitation.
      Specific antibody studies included virus neutralization assays for poliovirus
      antibodies, and enzyme-linked immunosorbent assay for diphtheria, tetanus,
      measles, rubella, varicella-zoster virus (VZV), and cytomegalovirus (CMV)
      antibodies. Avidity of rubella, VZV, and CMV antibodies was tested by enzyme
      linked immunosorbent assay modified to include a mild protein denaturant in the
      first wash after incubation with sera. RESULTS: All patients had a CD3+ cell
      count greater than 0.500 x 10(9)/L and a CD4+ cell count greater than 0.350 x
      10(9)/L). One patient had low proliferation responses to S. aureus, and one to
      phytohemagglutinin and pokeweed mitogen. Immunoglobulin levels, compared with
      those in age-related control subjects, were normal except that two patients had
      transient, borderline low IgG levels and two had elevated IgA levels. Specific
      antibody tests showed (No. of patients with positive results/No. tested) the
      following: diphtheria (13/13); tetanus (13/13); poliomyelitis caused by polio
      virus type 1 (5/9), type 2 (9/9), and type 3 (8/9); measles (11/13); rubella
      (11/13); and infection with VZV (5/5) and CMV (7/13). There were no significant
      differences in antibody avidity results between patients and control subjects for
      rubella (mean avidity index, 83.5 +/- 8.79 vs 85 +/- 17.6), VZV (81.6 +/- 3.98 vs
      65.1 +/- 12.38), or CMV (69.3 +/- 22.31 vs 73.3 +/- 12.46). CONCLUSIONS: Patients
      with "partial" DiGeorge anomalad, defined by clinical and immunologic criteria,
      can be immunized and for the most part can generate good antibody responses.

PMID- 7636648
TI  - Effect of priming with diphtheria and tetanus toxoids combined with whole-cell
      pertussis vaccine or with acellular pertussis vaccine on the safety and
      immunogenicity of a booster dose of an acellular pertussis vaccine containing a
      genetically inactivated pertussis toxin in fifteen- to twenty-one-month-old
      children. Italian Multicenter Group for the Study of Recombinant Acellular
      Pertussis Vaccine.
AB  - OBJECTIVE: To evaluate the safety and the immunogenicity of a booster dose of
      recombinant acellular pertussis vaccine combined with diphtheria and tetanus
      toxoids (DTaP, Biocine SpA) in 15- to 21-month-old children primed in infancy
      with either whole-cell diphtheria-tetanus-pertussis (DTwP) vaccine or DTaP
      vaccine. DESIGN: Open-label second phase of a double-masked, controlled trail,
      with masked analysis of serum samples. PARTICIPANTS AND SETTING: Three hundred
      fifty children, 15 to 21 months of age, who had been primed at 2, 4, and 6 months
      of age with either three doses of DTaP vaccine (n = 173) or DTwP vaccine (n =
      177). The children were enrolled in eight vaccination centers in Italy.
      INTERVENTIONS: All children received a booster dose of the DTaP vaccine and were
      examined for safety at 48 hours and at 7 days after vaccination. Serum samples
      for evaluation of immunogenicity were obtained from 196 (55%) of the 350
      children. MAIN OUTCOME MEASURES: IgG antibodies to pertussis toxin (Ptox),
      filamentous hemagglutinin, 69-kilodalton protein, and tetanus toxoid were
      measured by enzyme-linked immunosorbent assay. Pertussis toxin-neutralizing
      antibodies were measured by the Chinese hamster ovary cell toxin neutralization
      assay. MAIN RESULTS: Adverse reactions to DTaP were infrequent, and there was no
      difference in the incidence of local or systemic reactions in children given DTaP
      as a fourth dose in comparison with a first dose. One month after the DTaP
      booster vaccination, both groups had 6- to 40-fold increases in serum antibody
      concentrations to all antigens tested; the concentrations against the three
      pertussis antigens were higher in the DTaP-primed children (p < 0.05). The
      antibody titers to diphtheria and tetanus toxoids were higher in the DTwP-primed
      group (p < 0.05), but both groups had protective titers. The geometric mean ratio
      of anti-Ptox neutralizing antibody per unit of IgG anti-Ptox antibody was higher
      in the DTaP-primed group (p < 0.001). CONCLUSIONS: There are quantitative and
      qualitative differences in booster responses to DTaP vaccine in young children,
      depending on whether they were given DTaP or DTwP as primary immunization. This
      DTaP vaccine is safe and highly immunogenic as a booster.

PMID- 7636649
TI  - Evidence for partial growth hormone insensitivity among patients with idiopathic
      short stature. The National Cooperative Growth Study.
AB  - OBJECTIVE: To determine whether some patients with idiopathic short stature have
      partial resistance to growth hormone (GH). Patients with idiopathic short stature
      have decreased serum levels of the GH receptor-related GH-binding protein (GHBP),
      and low GHBP levels are associated with complete GH insensitivity (Laron)
      syndrome. We hypothesized that patients with idiopathic short stature and low
      GHBP levels may also have a degree of GH insensitivity. DESIGN: Retrospective
      analysis of patients in a multicenter study. SETTING: Ninety-six National
      Cooperative Growth Study centers in the United States and Canada. SUBJECTS: Five
      hundred eleven patients with idiopathic short stature who were treated with GH.
      All patients had a baseline height standard deviation score of less than -2 and a
      maximum stimulated GH level greater than 10 micrograms/L. Of these, 101 (20%) had
      a baseline GHBP standard deviation score of -2 or less. RESULTS: The patients
      with low GHBP levels, in comparison with those with normal GHBP levels, had a
      lower mean extracted standard deviation score for insulin-like growth factor I (
      3.3 +/- 1.1 vs -2.5 +/- 1.4; p < 0.0001) but mean 12-hour GH values (2.8 +/- 1.1
      vs 2.3 +/- 1.1 micrograms/L; p <0.0001). The differences between groups were
      statistically significant after control for age and weight-for-height standard
      deviation score. Among prepubertal patients, there was no significant difference
      between the low and normal GHBP groups in mean pretreatment or first-year growth
      rate (p = 0.74, 0.61 respectively) with comparable doses of GH. CONCLUSIONS:
      Patients with idiopathic short stature and low GHBP levels, compared with those
      with normal GHBP levels, had significantly lower standardized levels of insulin
      like growth factor I, and higher mean 12-hour GH levels, which suggest partial GH
      insensitivity. There was no significant correlation of GHBP levels with the
      growth response to exogenous GH.

PMID- 7636650
TI  - Magnetic resonance imaging in phenylketonuria: reversal of cerebral white matter
      change.
AB  - OBJECTIVES: To investigate the extent to which the abnormalities in cerebral
      white matter in adolescents and adults with phenylketonuria (PKU) are reversible.
      METHOD: Magnetic resonance imaging (MRI) of the brain was repeated in 41 patients
      with PKU (age range, 14 to 49 years) after an interval (median, 9 months; range,
      3 to 12 months) of dietary intervention. Scans were scored according to the
      extent of the white matter involvement. After an initial MRI, five patients
      returned to a strict low-phenylalanine diet with amino acid supplement; 21
      patients started a low-protein diet (1 gm/kg) with amino acids supplement; and 15
      patients made no dietary alteration. RESULTS: Scans improved in all five patients
      who returned to a strict low-phenylalanine diet, in 5 of the 21 patients on the
      low-protein diet plus amino acid supplement, and in 4 of the 15 patients who made
      no dietary change. There was a significant association between change in the MRI
      findings and in the blood phenylalanine concentration (Pearson correlation: r =
      0.55; p < 0.0002) and between change in the MRI and in the phenylalanine level at
      the time of the second scan (r = 0.58; p < 0.0001). Improvement was seen
      primarily in those in whom phenylalanine levels were reduced to less than 900
      mumol/L. There was no obvious change in MRI score after 3 weeks of strict
      phenylalanine restriction for the two adults who underwent serial scanning.
      CONCLUSION: The MRI changes in PKU are at least partially reversible by lowering
      the blood phenylalanine concentration.

PMID- 7636651
TI  - Effect of carbamazepine and valproate on bone mineral density.
AB  - OBJECTIVE: To examine the effect of carbamazepine and valproate monotherapy on
      bone mineral density in children. METHODS: Axial (second, third, and fourth
      lumbar vertebrae) and appendicular (distal third of radius) bone mineral density
      was measured by dual-energy x-ray absorptiometry in 27 healthy children and 26
      children with uncomplicated idiopathic epilepsy treated with either carbamazepine
      (n = 13) or valproate (n = 13) for more than 18 months. Control subjects and
      patients were similar with respect to age, race (all white), and geographic area,
      and had no dietary restrictions, neurologic impairment, or physical handicaps.
      RESULTS: Subjects were seizure-free for more than 6 months on a regimen of
      carbamazepine or valproate therapy, and had mean serum trough levels of 6.88 +/-
      2 micrograms/ml and 72.04 +/- 45.6 micrograms/ml, respectively. Dietary calcium
      intake was similar in control and treated groups. After correction for gender and
      age, children treated with valproate had a 14% (p = 0.003) and 10% (p = 0.005)
      reduction in bone mineral density at the axial and appendicular sites,
      respectively. The reduction in bone mineral density increased with the duration
      of valproate therapy. Carbamazepine did not significantly reduce bone mineral
      density. CONCLUSION: Valproate montherapy, but not carbamazepine therapy,
      significantly reduces axial and appendicular bone mineral density in children
      with idiopathic epilepsy and may increase their risk of osteoporotic fractures.

PMID- 7636652
TI  - Value of routine anaerobic blood cultures for pediatric patients.
AB  - OBJECTIVE: Anaerobic bacteremia rarely occurs in children. Therefore we assessed
      the usefulness of routinely obtaining anaerobic blood cultures in our pediatric
      patients. STUDY DESIGN: Records of 9360 paired aerobic anaerobic blood culture
      bottles (Bactec NR660 System) containing blood specimens from pediatric
      inpatients and outpatients at Duke University Medical Center, Durham, N.C., were
      reviewed retrospectively. Yield and speed of detection were calculated for each
      bottle and compared for statistical significance by the McNemar test. RESULTS: A
      total of 723 clinically important microorganisms were isolated; only 15 (2.1%)
      were strict anaerobes. Significantly more microorganisms (p < 0.001), especially
      staphylococci, nonfermenting gram-negative rods, enteric gram-negative rods, and
      yeasts, were detected by use of the aerobic bottle. The anaerobic bottle was
      important in identifying an anaerobic microorganism as the cause of sepsis in
      only five patients, all of whom were at increased risk of having anaerobic
      infection. CONCLUSIONS: Anaerobic blood cultures are rarely helpful in the
      majority of pediatric patients and usually show positive results only in clinical
      settings associated with anaerobic infection. Microorganisms that prefer an
      aerobic environment, such as Pseudomonas aeruginosa and yeasts, are now far more
      common than anaerobes in children; aerobic culturing of the entire volume of
      blood collected might increase the yield from pediatric blood cultures.

PMID- 7636653
TI  - Measuring resting energy expenditure in clinical practice.

PMID- 7636654
TI  - Early discharge of low birth weight infants: an opportunity to evolve and to
      create partnerships.

PMID- 7636655
TI  - Outcome in three siblings with antibody-mediated transient congenital
      hypothyroidism.
AB  - A woman receiving thyroxine substitution therapy for acquired hypothyroidism
      caused by autoimmune thyroiditis gave birth to three babies who had transient
      primary hypothyroidism. All three babies had elevated thyrotropin levels on
      neonatal screening, but one had normal thyroxine values. Thyrotropin receptor
      blocking antibodies were present in maternal serum and in the three neonates.
      Each baby also had a different congenital malformation. The neurodevelopmental
      outcome of the children appeared related in part to maternal thyroxine levels,
      which suggests that transplacental transfer of thyroxine may protect the fetal
      brain.

PMID- 7636657
TI  - Description and evaluation of a program for the early discharge of infants from a
      neonatal intensive care unit.
AB  - The effect of a cost-containment program focused on decreasing the lengths of
      hospital stay of high-risk neonates was assessed by comparison of discharge
      weights and lengths of stay for 257 study infants, discharged from a neonatal
      intensive care unit (NICU) after an early-discharge program began, with those of
      477 control infants discharged during a prior 1-year period. Demographic data and
      costs, as well as data on emergency department use and hospital readmissions,
      were included in the comparisons. There was a significant decrease in mean
      discharge weight and length of stay for infants in the study group. During a 7
      month period, an estimated 2073 days of hospital care and approximately
      $2,700,000 in hospital charges were saved, or $10,609 per infant discharged. The
      cost of instituting and maintaining the program was $120,413, or $468 per infant.
      Seven visits were made to the emergency department by the study infants during
      the first 14 days after discharge. One infant was readmitted for a 4-day hospital
      stay for suspected sepsis. Significantly earlier discharge of high-risk neonates
      produced a decrease in hospital charges without causing excessive morbidity. The
      success of the program was coincident and presumed related to the institution of
      multiple elements focused toward family support through early-discharge planning.
      The reduction in hospital charges was 30 times higher than program expenses.

PMID- 7636656
TI  - Effect of hepatitis C genotype on mother-to-infant transmission of virus.
AB  - We evaluated vertical transmission of hepatitis C virus (HCV) in 37 pregnant
      women, 20 of whom also had human immunodeficiency virus (HIV) antibody. The HCV
      subtypes 1a and 3a were prevalent among pregnant women with HIV infection.
      Infection with HCV was transmitted from 30.7% of the 13 mothers with HCV
      ribonucleic acid (RNA) and HIV antibody and from 25% of the 8 with HCV RNA alone.
      No mother with HCV antibody but no HCV RNA transmitted HCV to her infant.
      Subtypes 1b and 3a seemed to be the most common HCV genotypes transmitted.

PMID- 7636658
TI  - Follow-up of very low birth weight infants after erythropoietin treatment to
      prevent anemia of prematurity.
AB  - OBJECTIVE: Treatment with recombinant human erythropoietin (rHuEPO) stimulates
      erythropoiesis and reduces the need for transfusions in hospitalized preterm
      infants. The aim of our study was to follow very low birth weight infants after
      the initial 6 weeks of rHuEPO treatment. DESIGN AND METHODS: We randomly assigned
      97 very low birth weight infants with a gestational age of 31 weeks or less and
      birth weight of 1500 gm or less to receive rHuEPO, 300 units/kg per week
      (erythropoietin (EPO) 300, n = 33), rHuEPO, 750 units/kg per week (EPO 750; n =
      28), or no treatment (control, n = 36). The rHuEPO was administered from the
      first week of life for 6 weeks. After EPO therapy was discontinued, 75 neonates
      were followed weekly until discharge and at 3, 6, and 12 months of age. RESULTS:
      Mean numbers (+/- SD) of packed erythrocyte transfusions per patient from the
      time rHuEPO therapy was discontinued until discharge were 0.38 +/- 0.64 (EPO
      300), 0.23 +/- 0.52 (EPO 750), 0.9 +/- 1.1 (control) (p < 0.05 in both EPO groups
      vs control). Mean reticulocyte counts at the sixth week were 6% +/- 2.2% (EPO
      300), 6.9% +/- 2.2% (EPO 750), and 3.1% +/- 2.6% (control) in the three groups (p
      < 0.01 in both EPO groups vs control), and at the eighth week were 4.7% +/- 2.8%
      (EPO 300), 5.4% +/- 2.7% (EPO 750), and 2.6% +/- 2.2% (control) (p < 0.01 in both
      EPO groups vs control). Serum ferritin levels were significantly higher at the
      sixth week, and the percentage of hemoglobin F was significantly lower at 6, 8,
      and 10 weeks in the control group versus EPO groups. At 3, 6, and 12 months of
      age, there were no differences in reticulocytes, ferritin, HbF, and growth among
      groups. CONCLUSION: Preterm infants who received rHuEPO had a normal pattern of
      erythropoiesis after the drug was discontinued. These data provide strong
      evidence that the anemia of prematurity is the result of a transient
      developmental abnormality in EPO production.

PMID- 7636659
TI  - Differentiation of segmented and band neutrophils during the early newborn
      period.
AB  - This prospective study evaluated the degree of inter-reader variability in the
      identification of segmented and band neutrophils from blood smears of full-term,
      healthy neonates. Wide inter-reader differences of band neutrophil identification
      and the immature to total neutrophil ratio were observed. Because of poor
      correlation between evaluators of the same blood smear, the clinical utility of
      the manual differential leukocyte count in the evaluation of neonates is limited.

PMID- 7636660
TI  - Twenty-seven years of experience with oral vitamin K1 therapy in neonates.
AB  - Healthy term infants born at the University of Missouri have received vitamin K
      prophylaxis as a single oral dose since 1967. A retrospective study was
      undertaken to determine whether either hemorrhagic disease of the newborn or any
      unexplained intracranial hemorrhage occurred in an infant who received orally
      administered vitamin K, but none could be found in three separate databases. We
      conclude that we have met our duty of providing appropriate care.

PMID- 7636661
TI  - Pitfalls in newborn hemoglobinopathy screening: failure to detect beta(+)
      thalassemia.
AB  - Although universal newborn screening can reliably identify all infants with
      sickle cell hemoglobinopathies, the initial screening result must not be
      considered the definitive diagnosis. We describe 23 infants whose screening
      phenotype was FS or FC but whose true phenotype included hemoglobin A,
      establishing a definitive diagnosis of hemoglobin S or hemoglobin C in
      combination with beta(+)-thalassemia. Higher than expected hemoglobin
      concentrations or lower than expected mean erythrocyte volumes should suggest
      concurrent beta(+)-thalassemia.

PMID- 7636662
TI  - Reduced neonatal liver iron concentrations after uteroplacental insufficiency.
AB  - Neonatal liver (storage) but not heart (nonstorage) tissue iron concentrations
      were reduced by 60% at autopsy in 15 newborn infants who had gestations
      complicated by uteroplacental insufficiency because of maternal hypertension or
      Potter syndrome. The hepatic iron reductions in term and preterm infants, and
      with either antecedent condition, were similar.

PMID- 7636663
TI  - Aggressive respiratory support and unilateral nephrectomy for infants with severe
      perinatal autosomal recessive polycystic kidney disease.
AB  - Newborn infants with severe autosomal recessive polycystic kidney disease often
      receive minimal intervention because poor respiratory and renal outcomes are
      anticipated. We describe two patients whose respiratory failure was successfully
      treated with aggressive intervention. Massive kidneys restricted gastrointestinal
      capacity and limited feedings. Uninephrectomy allowed adequate enteral feedings
      and preserved sufficient renal function for homeostasis and growth.

PMID- 7636664
TI  - Superior vena cava obstruction after extracorporeal membrane oxygenation.
AB  - Of 60 neonates who survived extracorporeal membrane oxygenation (ECMO) in our
      institution between June 1992 and March 1994, seven had either complete or
      partial superior vena cava (SVC) obstruction. When the patients with SVC
      obstruction were compared with those who had an echocardiogram after ECMO, no
      predisposing factors for the development of SVC thrombus could be found. Our data
      show that SVC thrombus may be a significant complication after ECMO.

PMID- 7636665
TI  - Intraarticular corticosteroids for chronic arthritis in children: efficacy and
      effects on cartilage and growth.
AB  - OBJECTIVES: To assess the efficacy and effects on cartilage and statural growth
      of intraarticular corticosteroid (IAS) therapy for chronic arthritis in children
      and adolescents. METHODS: We examined 21 children and adolescents with chronic
      arthritis (median duration, 8 months) that did not respond to nonsteroidal
      antiinflammatory drugs. The 21 joints injected with triamcinolone-hexacetonide
      were examined before and 7 weeks after IAS therapy by gadolinium-enhanced
      magnetic resonance imaging; 14 joints were also examined 13 months after IAS
      therapy. RESULTS: All joints treated with IAS had improvement. Magnetic resonance
      imaging showed long-lasting suppression of inflammation and pannus without
      evidence of toxic effects on cartilage. Statural growth was not affected.
      CONCLUSION: In experienced hands, IAS therapy may be a safe and effective tool in
      the treatment of chronic arthritis in childhood. Long-term follow-up is
      mandatory.

PMID- 7636666
TI  - Oropharyngeal candidiasis in immunocompromised children: a randomized,
      multicenter study of orally administered fluconazole suspension versus nystatin.
      The Multicenter Fluconazole Study Group.
AB  - OBJECTIVE: To compare the efficacy, safety, and tolerance of fluconazole
      suspension versus nystatin in the treatment of oropharyngeal thrush in
      immunocompromised children. DESIGN: Multicenter, randomized, observer-masked
      trial. SETTING: Thirty-two centers participated, including hospitals and
      ambulatory care clinics. PATIENTS: We enrolled 182 immunocompromised infants and
      children, ages 5 months to 14 years, with signs of oral thrush and presence of
      yeasts on potassium hydroxide- or gram-stained preparations. Subjects were
      randomly assigned to receive a single daily dose of fluconazole suspension, 2 to
      3 mg/kg per day, or nystatin, 400,000 units four times daily for 14 days; 159
      patients, who had culture confirmation of thrush and received at least 7 days of
      study drug, were evaluated for efficacy; all patients were evaluated for safety.
      RESULTS: Clinical cure was demonstrated in 91% of the subjects in the fluconazole
      group and 51% of the subjects in the nystatin group (p < 0.001), and eradication
      of the organism cultured at entry occurred in 76% and 11% (p < 0.001),
      respectively. Gastrointestinal conditions developed in six patients who received
      fluconazole and in three who received nystatin; two fluconazole recipients were
      subsequently withdrawn from the study. Laboratory abnormalities occurred with
      equal frequency in both groups. Clinical relapse rates were similar in both
      groups at 2 weeks (18% and 24% for fluconazole and nystatin, respectively) and 1
      month (28% and 27%, respectively) after the completion of study drug.
      CONCLUSIONS: Fluconazole suspension is more effective than nystatin in the
      treatment of thrush in immunocompromised children. Both regimens were well
      tolerated.

PMID- 7636667
TI  - Neuroblastoma-associated opsoclonus-myoclonus treated with intravenously
      administered immune globulin G.
AB  - An 18-month-old black girl had progressive truncal ataxia, opsoclonus, and
      multifocal myoclonus associated with a nonresectable abdominal
      ganglioneuroblastoma. Before chemotherapy, she received intravenously
      administered IgG, 1 gm/kg, for 2 days; within 48 hours of the first dose, there
      was significant improvement of the opsoclonus-myoclonus and ataxia. She required
      a 1 gm/kg maintenance dose every 4 to 6 weeks for a total of 12 doses, but is now
      free of symptomatic after 2 years with no therapy.

PMID- 7636668
TI  - Acuity versus acuteness of illness.

PMID- 7636669
TI  - Home medical care for children.

PMID- 7636670
TI  - Relation of renal and cerebral blood flow in growth-retarded fetuses and in
      neonates after hypoxia.

PMID- 7636671
TI  - Microcornea, glaucoma, and absent frontal sinus.

PMID- 7636672
TI  - Prognostic value of hyperlactatemia in neonates.

PMID- 7636673
TI  - Prognostic value of hyperlactatemia in neonates.

PMID- 7636674
TI  - Urinary free cortisol values in children under stress.

PMID- 7636675
TI  - Progression of premature thelarche to precocious puberty.

PMID- 7636676
TI  - Fiberoptic versus conventional phototherapy for neonatal hyperbilirubinemia.

PMID- 7636677
TI  - Development of a vaccine tracking system to improve the rate of age-appropriate
      primary immunization in children of lower socioeconomic status.

PMID- 7636678
TI  - Management of chronic viral hepatitis in children.
AB  - Chronic viral hepatitis is prevalent worldwide in the pediatric population and
      can be associated with significant morbidity and mortality. Acquisition of
      disease in early childhood may predispose children to long-term complications,
      including cirrhosis and HCC. Efforts should be made to recognize, control, and
      prevent further spread of these infections, especially in areas where hepatitis
      is endemic. Alpha interferon therapy hastens disease remission in a proportion of
      patients with chronic hepatitis B. Further studies are needed to define the role
      of interferon in chronic HDV and HCV infection in children.

PMID- 7636679
TI  - Defective biliary secretion during total parenteral nutrition: probable
      mechanisms and possible solutions.
AB  - Cholestasis associated with TPN is now diminishing in frequency. One factor is
      likely to be the early initiation of oral feeding. One of the effects of oral
      intake is to restore the enterohepatic circulation of bile acids. This in turn
      promotes lipid absorption, which leads to improved nutrition and a decreased in
      mucosal atrophy. The role of the enterohepatic cycling of bile acids has been
      explored in this review. In infants or children on TPN who have bile acid
      malabsorption, UDCA can be used to correct decreased secretion of endogenous bile
      acids. However, controlled studies showing that UDCA actually decreases
      moribidity and mortality in infants on prolonged TPN have not yet been performed
      and they are sorely needed. UDCA is nontoxic and acts as a natural bile acid
      after conjugation. An improved formulation of UDCA with rapid and efficient
      intestinal absorption has been developed, but the optimal formulation of UDCA is
      still not available. Cholylsarcosine, a new conjugated bile acid analogue that
      has been developed as a bile acid replacement agent, improves lipid absorption in
      animals with steatorrhea caused by bile acid malabsorption and intestinal
      resection. However, this compound has not been tested clinically.

PMID- 7636680
TI  - Lessons in complexity: mycobacterial infections in the pediatric liver transplant
      recipient.

PMID- 7636681
TI  - Intestinal microbial bile acid transformation in healthy infants.
AB  - Following the establishment of functionally active intestinal flora in three
      healthy Swedish children from birth up to 24 months of age, we investigated the
      development of different 24-carbon bile acids. The fecal bile acids were group
      separated into unconjugated, glycine-conjugated, taurine-conjugated, and
      sulfated, so that we could follow the changes between the different fractions of
      conjugates. In meconium, most (55-63%) of the bile acids were conjugated with
      taurine; only 11-32% were conjugated with glycine. Deconjugation was the first
      sign of intestinal microbial activity on the bile acids. Already at 1 month of
      age, most of the bile acids were deconjugated; among the conjugated bile acids,
      the glycine-conjugated dominated over the taurine-conjugated. An unidentified
      conjugate of cholic and chenodeoxycholic acids (C, CDC) that separated with the
      sulfated bile acids was found. The unconjugated bile acids and those that arose
      from hydrolysis of existing conjugates were separated and identified by gas
      liquid chromatography coupled to mass spectrometry (GC-MS). Twenty-nine different
      bile acids were identified. In meconium, 16 different bile acids were identified.
      C and CDC were identified in all samples. The bile acid pattern changed during
      the course of the study. Many of the identified bile acids were only found in one
      or a few of the analyzed samples, and sometimes only in samples from one child. 6
      alpha-hydroxylated bile acids, probably not microbially synthesized, were present
      at high percentages in the children.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7636683
TI  - A packaged rice-based oral rehydration solution for acute diarrhea.
AB  - In a 12-month community study in Ecuadorian preschool children, we compared a
      packaged rice-based oral rehydration solution (R-ORS) that contained 160 g of
      rice flour and 12 g of sucrose per liter as well as electrolytes and alpha
      amylase, and required cooking before consumption, to the standard glucose
      electrolyte oral rehydration solution (G-ORS) for the treatment of acute
      noncholera diarrhea. The reconstituted R-ORS had energy and protein contents of
      620 kcal/L and 12g/L, respectively, and an osmolarity of 230 mosm/L. In all, 156
      cases were treated with the R-ORS and 144 with the standard G-ORS. Cases treated
      with R-ORS had a significantly shorter duration of diarrhea (p < 0.0001; median;
      34 h versus 48 h), a lower number of stools (p < 0.001; median; four versus
      seven), and a greater weight gain after 4 days of treatment (p < 0.05; mean; 1.6%
      versus-0.2%) than those treated with G-ORS. ORS and total liquid intakes tended
      to be higher with the R-ORS. The two ORS were equivalent for the correction of
      mild dehydration and the maintenance of normal hydration status.

PMID- 7636682
TI  - Levels of peptidoleukotriene E4 are elevated in active Crohn's disease.
AB  - Proinflammatory mediators, including leukotriene (LT) B4, are elevated in the
      intestinal mucosa in active chronic inflammatory bowel diseases (IBD). LTE4 is
      the major peptidoleukotriene metabolite and it is stable in urine. The aim of
      this study was to measure LTE4 levels in the urine of 27 children with Crohn's
      disease and 27 control subjects including 12 children with functional recurrent
      abdominal pain and 15 unaffected siblings of IBD patients. LTE4 levels were
      measured in urine using high-performance liquid chromatography separation and
      radioimmunoassay with specific antibody. The Pediatric Crohn's Disease Activity
      Index and physician global assessment were used to categorize patient groups. C
      reactive protein, orosomucoid, and erythrocyte sedimentation rate were employed
      as laboratory markers of mucosal inflammation. Urinary LTE4 levels were elevated
      in the 13 children with active Crohn's disease (160.5 +/- 59.4 pg/ml; mean +/-
      SEM) compared with both levels in the 14 patients with inactive disease (67.1 +/-
      18.1 pg/ml; p < 0.05) and controls (45.0 +/- 10.9 pg/ml; p < 0.05). We conclude
      that measurement of urinary LTE4 is a useful test for monitoring the activation
      of peptidoleukotrienes in patients with Crohn's disease. It provides a
      noninvasive, objective adjunct for assessment of disease activity and could be
      employed in future trials examining the role of the leukotriene inhibitors in the
      medical therapy of IBD.

PMID- 7636684
TI  - Comparison of an oral rice-based electrolyte solution and a glucose-based
      electrolyte solution in hospitalized infants with diarrheal dehydration.
AB  - This randomized trial compared the efficacy of a rice-based (50 g/L) oral
      rehydration solution with the standard glucose-based WHO/UNICEF solution in the
      treatment of 100 hospitalized infants, ages 3-18 months, with acute dehydrating
      diarrhea. The main outcomes examined were stool output and duration of diarrhea.
      Patients were placed on a "metabolic" bed so that intake and losses could be
      measured accurately throughout the study. Overall, 89% of patients were
      successfully rehydrated orally; the rehydration failure rate was similar in the
      two groups and it was significantly associated with infection by specific E. coli
      serotypes. Stool output in the first 24 h was 11% lower in the rice group (112
      versus 126 ml/kg), but this difference was not significant. Neither stool output
      in the second 24 h nor total stool output were different between groups. The
      median duration of diarrhea was 3.8 days in the rice group and 3.9 days in the
      glucose group (p = NS). Other (secondary) outcomes, such as fluid intake, urine
      output, emesis losses, weight change, and electrolyte balance were also similar
      between the two groups. Some evidence of carbohydrate malabsorption was detected
      in 61% of the rice group versus 45% of the glucose group (p = NS) and was not
      associated with any particular treatment outcome. These results show that a rice
      based oral rehydration solution is as efficacious as, but not better than the
      standard glucose-based solution in the treatment of infants with acute
      dehydrating diarrhea not associated with cholera.

PMID- 7636686
TI  - Lipoprotein abnormalities in two children with minimal biliary excretion.

PMID- 7636685
TI  - Mycobacterial infections after pediatric liver transplantation: a report of three
      cases and review of the literature.

PMID- 7636687
TI  - Recurrent abdominal pain in a patient with cystic fibrosis and type IV
      hyperlipidemia.

PMID- 7636688
TI  - Rectal duplication cyst.

PMID- 7636689
TI  - Life-threatening esophageal variceal bleeding after air transport to a liver
      transplantation center in a child with extrahepatic biliary atresia.

PMID- 7636690
TI  - Breast milk-induced allergic colitis.

PMID- 7636692
TI  - Update on a child with bilateral posterior lenticonus.

PMID- 7636691
TI  - Study needs more statistical power.

PMID- 7636693
TI  - Levodopa/carbidopa treatment for amblyopia in older children.
AB  - The purpose of the present study is to determine how long visual function
      improves during levodopa/carbidopa with part-time occlusion treatment in older
      amblyopic children. A 7-week open clinical trial of levodopa (0.55 mg/kg, three
      times daily) with 25% carbidopa combined with part-time occlusion (3 hours/day),
      was undertaken in 15 older (mean age, 8.87 years) amblyopic children. Visual
      acuity, fusion, and stereo acuity were measured at baseline, at weeks 1, 3, 5,
      and 7 during treatment, and 6 weeks following the end of all treatment. Health
      status was assessed by physical examination, questionnaire, and standard
      laboratory tests (CHEM 20, complete blood cell count [CBC], and differential).
      The results revealed that visual acuity in the amblyopic eye improved for 5
      weeks, from 20/170 at baseline to 20/107, then stabilized for the last 2 weeks.
      Visual acuity also improved in the dominant eye by 0.6 lines, from 20/19 to
      20/16. At the 6-week follow up, visual acuity in the amblyopic eye remained at
      20/107 (paired t = 4.78, df = 14, P < .001), a 37% improvement. Thirty-three
      percent of the subjects demonstrated improved fusion from baseline to the 7-week
      trial that was maintained at follow up (chi 2 = 3.97, P < .05). Stereo acuity did
      not significantly change. Physical exam (blood pressure, body temperature,
      respiration, heart rate) and standard laboratory tests remained normal and side
      effects were minimal.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7636694
TI  - Outcome of sixth nerve palsy or paresis in young children.
AB  - This study evaluated the ophthalmological outcome following sixth nerve palsy or
      paresis in 64 children 7 years of age and younger. The outcomes considered were
      vision, residual strabismus and the need for strabismus surgery. Etiologies
      included tumor, hydrocephalus, trauma, infection, malformation, and idiopathic
      and miscellaneous causes. Strabismus surgery was performed on 24% of the
      patients, with residual strabismus present in 66% of the patients. Neurologists
      and ophthalmologists should monitor visual acuity in these young children at
      frequent intervals be prepared to institute amblyopia therapy early in the course
      of the ocular misalignment if permanent visual disability is to be avoided.

PMID- 7636695
TI  - Facial asymmetry and tendon laxity in superior oblique palsy.
AB  - Both facial asymmetry and superior oblique tendon laxity are associated with
      congenital superior oblique muscle palsy (SOP). It is unknown whether facial
      asymmetry and tendon laxity are related to each other, perhaps even causally. We
      evaluated 29 patients with SOP for presence of facial symmetry, tendon laxity, or
      both, and correlated these findings with presence or absence of chronic head
      tilt. Sixteen of 21 (76%) unilateral congenital SOP patients had facial asymmetry
      and 17 (81%) had tendon asymmetry. Ninety-four percent had either or both
      abnormalities, but only 57% had tendon laxity (palsy) on the side opposite the
      facial hypoplasia. All patients with facial hypoplasia had a head tilt toward the
      hypoplastic side of the face, regardless of which side the palsy was on. These
      findings, along with previous studies of congenital muscular torticollis, infer
      that the two anatomic abnormalities associated with congenital SOP (facial
      asymmetry and tendon asymmetry) do not occur as part of the same developmental
      sequence, but the facial asymmetry develops as a consequence of a chronic head
      tilt from a young age.

PMID- 7636696
TI  - Should early strabismus surgery be performed for ocular torticollis to prevent
      facial asymmetry?
AB  - To help determine whether ocular torticollis causes facial asymmetry, we analyzed
      photographs of patients with long-standing head tilts for amounts of tilt and
      facial asymmetry. Significant facial asymmetry that correlated with the side of
      the head tilt was found in patients with congenital superior oblique muscle
      paresis, but not in patients with traumatic superior oblique muscle paresis nor
      in patients with dissociated vertical deviation. The mechanism explaining the
      development of facial asymmetry in these patients may be deformational molding of
      the face and skull from the infant's sleeping with its head turned predominantly
      to one side during the first 6 to 12 months of life. Early strabismus surgery to
      correct the head tilt may help prevent facial asymmetry, but ensuring that the
      infant sleeps with alternating head positions may be more important.

PMID- 7636697
TI  - Vertical shift of the medial rectus muscles in the treatment of A-pattern
      esotropia: analysis of outcome.
AB  - A retrospective study was performed on 18 consecutive patients with A-pattern
      esotropia and no apparent oblique muscle dysfunction, mechanical restriction,
      paresis, or previous muscle surgery. All patients underwent graded bilateral
      medial rectus recession for their esotropia with simultaneous vertical upshift to
      treat the A-pattern. The quantitative relationship between amount of upshift,
      amount of A-pattern correction, preoperative A-pattern, and preoperative
      esotropia was examined. We found that the amount of A-pattern correction was
      closely correlated with the size of the A-pattern preoperatively (r = 0.83),
      independent of amount of upshift. While the change in A-pattern did correlate
      with the amount of the upshift (r = 0.60), it was not a significant independent
      predictor of the surgical response. The amount of recession had little influence
      on the effectiveness of the procedure in correcting the vertical incomitance, and
      the transposition did not seem to affect the correction of the basic esotropia,
      adversely. We conclude that medial rectus recession with vertical upshift of the
      muscle insertions is an effective procedure for correcting the vertical
      incomitance in A-pattern esotropia, and that the amount of A-pattern correction
      achieved is determined primarily by the size of the preoperative A-pattern and
      not the amount of upshift.

PMID- 7636698
TI  - Effectiveness of inferior transposition of the horizontal rectus muscles for
      acquired inferior rectus paresis.
AB  - Full inferior transposition of the horizontal recti (inverse Knapp procedure) was
      performed on four patients with unilateral inferior rectus muscle weakness. The
      patients were followed up over time to determine the medium- and long-term
      effectiveness of the procedure. All of the patients had single binocular vision
      without the use of prisms in the primary position of gaze and three in the
      reading position after a mean postoperative follow-up interval of 21/2 years. The
      mean primary position preoperative vertical deviation was 20.3 delta and the mean
      primary position postoperative vertical correction was 19.5 (range, 16 to 24)
      delta. The field of binocular single vision was assessed quantitatively and
      scored 2.4% preoperatively compared with 52.3% postoperatively. There was no
      decrease in the effect of the procedure over time. Additional surgery may still
      be required to correct symptomatic residual vertical down-gaze diplopia.

PMID- 7636699
TI  - Subretinal neovascularization in children and adolescents.
AB  - Subretinal neovascular membranes (SRNVM) in the pediatric population are rare.
      The clinical presentation, etiology, course, and management of SRNVM in 25
      children (27 eyes) were studied retrospectively. Inflammatory or infectious
      conditions predominated (10 of 25). Eleven of 19 untreated SRNVM (58%)
      spontaneously involuted, with 9 of these 11 achieving a final visual acuity of
      20/50 or better. A hyperpigmented ring on fluorescein angiography was associated
      with 9 of the 11 involuted SRNVM. The presence of this pigmented ring may help to
      identify those cases with a better visual prognosis.

PMID- 7636700
TI  - Unilateral surgery for exotropia with convergence weakness.
AB  - We prospectively studied 14 patients whom we treated surgically for exotropia
      (XT) with convergence weakness measuring at least 8 delta for distance (6 m) that
      increased at least 8 delta at near (1/3 m). Surgery involved lateral rectus
      recessions and medial rectus strengthenings (advancements or resections) to
      eliminate distance and near deviations and simultaneously collapse near-distance
      differences. The medial rectus was strengthened more than the lateral rectus was
      recessed; amounts were based on the near deviation. Minimum follow-up was 6
      months after surgery. Preoperatively, the mean XT at distance was 18.3 delta
      (range, 8 to 35 delta) and at near 30.1 delta (range, 16 to 50 delta). At latest
      follow-up evaluations the mean distance deviation was 0.1 delta XT and at near
      1.8 delta XT. The near-distance differences were reduced by a mean of 10.2 delta;
      the mean postoperative difference was 1.7 delta. Unilateral surgery for XT with
      convergence weakness biased to medial rectus strengthening and geared to near
      deviation can successfully collapse the near-distance differences while
      satisfactorily aligning both distance and near fixation. This surgery has low
      risk of creating long-term postoperative esodeviations at distance.

PMID- 7636701
TI  - Measurement of low vision in advanced cicatricial retinopathy of prematurity.
AB  - This study evaluates functional vision in visually impaired children with stage
      IV to V cicatricial retinopathy of prematurity (CROP) by comparing results
      derived from the Teller acuity cards and a battery of behavioral tasks, the
      visual function battery (VFB). Vision was evaluated in 26 eyes of 15 children
      ages 6 months to 14 years, who underwent retinal reattachment procedures for
      active stage IV and stage V retinopathy of prematurity. Results showed that 10 of
      26 eyes (38%) had a recordable grating acuity to Teller acuity card assessment.
      Twenty-five of 26 eyes (96%) showed a response to the VFB. Sixteen of 26 eyes
      (62%) showed recordable scores with the VFB but no corresponding scores with the
      Teller acuity cards. The VFB may be more reliable than the Teller acuity cards in
      measuring visual function in the very low acuity range.

PMID- 7636702
TI  - Botulinum A toxin treatment of a deviated orbital implant.
AB  - We report a case of progressive deviation of an implant that resulted in
      conjunctival thinning and an inadequately fit prosthesis. Such a case may have
      been treated with conjunctival grafting or replacement of the implant with an
      hydroxyapatite sphere. In this case, injection of botulinum A toxin (Botox) into
      the contracted medial rectus muscle contributed to the successful refitting of a
      new and stable prosthesis and improvement of the conjunctival integrity. Possible
      explanations of the progressive shift in the position of the implant and its
      postinjection stability are discussed.

PMID- 7636704
TI  - Crawford tubes (with suture) secured with absorbable suture.

PMID- 7636703
TI  - Interstitial keratitis as presenting ophthalmic sign of sarcoidosis in a child.
AB  - Interstitial keratitis is a rarely occurring sign in sarcoidosis. We report a
      case of childhood sarcoidosis with initial ocular presentation as interstitial
      keratitis. Erythema nodosum preceded the ocular findings by 4 years and arthritis
      developed 1 year after ocular findings developed. Although no history of
      intraocular inflammation was present, there was evidence of inactive
      chorioretinitis and vitritis found at initial presentation. Systemic steroids
      were used to treat the patient's skin lesions and topical steroids to treat his
      corneal inflammation. He developed posterior uveitis and optic nerve edema both
      of which were responsive to oral steroids. Two years after the presentation of
      his ocular findings, the onset of pulmonary symptoms and resultant transbronchial
      biopsy confirmed his diagnosis of sarcoidosis.

PMID- 7636705
TI  - Bilateral monocanalicular silicone loop: predictable home removal of nasolacrimal
      stents.
AB  - Premature dislocation, a potential disadvantage of conventional, unilateral
      silicone intubation for lacrimal disease, can be alleviated with a firmly-tied,
      bilateral, superior canaliculus intubation. Since the looped silicone stent can
      be removed easily at home by parents, this technique is particularly beneficial
      for remote patients for whom postoperative, clinic removal is a financial burden.

PMID- 7636706
TI  - Acronyms of major cardiologic trials--1994.

PMID- 7636707
TI  - Comparison of pregnancy symptoms of infertile and fertile couples.
AB  - This study was undertaken to describe the most common symptoms experienced during
      pregnancy by couples with a history of infertility and to compare them with
      symptoms of expectant couples without a history of reproductive problems. The
      Symptomatology Inventory, a 42-item checklist of common pregnancy symptoms, was
      used. The 10 most frequent symptoms reported and their rank order were very
      similar for the women from both groups. Men from the two groups frequently
      reported similar symptoms, but differed on their rank order. This research
      provides evidence that in terms of pregnancy symptoms infertile and fertile
      couples are more alike than they are different.

PMID- 7636708
TI  - Delayed initiation of breast-feeding the preterm infant.
AB  - It is well documented that mother's milk is the best source of nutrition for the
      preterm infant. However, mothers of preterm infants face obstacles during the
      early stages of the breast-feeding experience. This study examined the
      experiences of 13 mothers whose preterm infants initiated suckling at the breast
      on day 14 or later after birth. Eight weeks after delivery, six infants were
      exclusively receiving mother's milk, four were receiving mother's milk and
      formula, and three infants had been weaned entirely from mother's milk. Some of
      the problems encountered by these mothers may have been averted with input from
      health professionals with special knowledge in breast-feeding the preterm infant.
      A clinical pathway for breast-feeding preterm infants is presented.

PMID- 7636709
TI  - Perinatal outcomes management: balancing quality with cost.
AB  - As flexibility and change become the only constants in health care delivery,
      providers are seeking improved methods for delivering quality, cost-effective
      services. Perinatal care is no exception. Length of stay is decreasing for
      obstetric patients, and the challenges of providing quality care are great.
      Outcomes management uses outcomes measures to improve clinical and functional
      results while better utilizing resources. Critical pathways and variances from
      that pathway are analyzed for opportunities to improve care and quality. Quality
      indicators are then derived from the variance data. The women's services outcomes
      manager, a new role, identifies and resolves quality issues.

PMID- 7636710
TI  - Clinical nursing management of sickle cell disease and trait during pregnancy.
AB  - Sickle cell-related hemoglobinopathies present challenges for clinical management
      during pregnancy, labor, delivery, and the postpartum course because perinatal
      morbidity remains a significant practice concern. Nursing strategies that strive
      for synthesis of knowledge pertaining to pathophysiology, genetic counseling,
      life events that have affected the patient's health history, treatment
      modalities, and psychosocial needs may improve obstetric and neonatal outcomes.
      Clinical management strategies for the prenatal, intrapartum, and postpartum
      courses are provided. Nursing intervention strategies such as follow-up teaching,
      involvement of the partner and support network in aspects of care, and patient
      advocates, in conjunction with independent nursing practice activities involving
      emotional support and measures to alleviate symptoms associated with disease
      manifestations, are cornerstones in the contribution of nursing to the
      multidisciplinary care of the pregnant woman with sickle cell disease and trait.

PMID- 7636711
TI  - Patient assessment skills: assessing early cues of necrotizing enterocolitis.
AB  - A study is presented utilizing the critical decision method to elicit knowledge
      from neonatal intensive care unit nurses regarding the assessment of infants at
      risk for necrotizing enterocolitis. Researchers were successful in eliciting
      knowledge not available in current nursing texts, including a framework for
      considering necrotizing enterocolitis and problem-solving strategies used by
      experienced nurses. Implications for nurse instruction and potential applications
      of this information are discussed.

PMID- 7636712
TI  - A comparison of methods for estimating the weight of preterm infants.
AB  - Four methods of predicting a preterm infant's weight (upper mid-arm
      circumference, gestational age, tape measure nomogram, and guessing) were
      investigated to see which was the most accurate. The weights of 37 preterm
      neonates were initially guessed by an experienced clinician, then estimated by
      the other three approaches applied in a random order, and then confirmed through
      actual weighing. The correlations between the four estimated weights and the
      actual weights were .96, .84, .97, and .98, respectively. The tape measure
      nomogram method was the best overall approach for clinical use.

PMID- 7636713
TI  - Biorhythms in infants and role of the care environment.
AB  - All physiologic functions demonstrate cyclic activity. Infant development
      includes maturation of biorhythms. Two basic changes in biorhythm include
      establishment of circadian rhythm and day-night pattern. Biorhythms are driven by
      internal pacemakers yet are highly susceptible to environmental influences. Sleep
      wake pattern and body temperature rhythm are two examples of infant biorhythms
      that demonstrate significant change with development. Biorhythm is the scientific
      basis for interventions (such as cycled lighting, feeding schedule, and
      caregiving pattern) aimed at improving the fit between infant and the
      environment.

PMID- 7636714
TI  - delta 9-Tetrahydrocannabinol (THC) causes the variable expression of IL2 receptor
      subunits.
AB  - Previously, we reported that the cannabinoid delta 9-tetrahydrocannabinol (THC)
      suppressed interleukin 2 (IL2)-induced proliferation of a cloned, natural killer
      like cell line (NKB61A2) and decreased the number of high- and intermediate
      affinity IL2 binding sites. However, the surface expression of interleukin 2
      receptor alpha (IL2R alpha) chain, as measured by flow cytometry, was increased
      rather than decreased by THC treatment. This suggested that the drug-induced
      deficiency in IL2 binding and cell activation involved a defect in the cell
      surface expression of IL2R subunits other than the alpha chain. Because the IL2
      receptor complex is composed of alpha, beta and gamma chains, we examined the
      effect of THC treatment on the expression of these chains. In a result consistent
      with our previous findings, we observed that treatment of NKB61A2 cells with THC
      increased the cellular immunoprecipitable IL2R alpha protein (p55) and mRNA.
      Furthermore, the cellular production of IL2R beta chain protein (p75) and mRNA,
      determined by immunoprecipitation and Northern blotting, respectively, was also
      increased. The mRNA stability assay showed that THC increased the stability of
      IL2 beta mRNA, and nuclear run-on experiments suggested that the increase in
      subunit production was not due to a drug effect on gene transcription. The IL2R
      gamma chain was also affected by THC treatment in that Northern blotting studies
      showed a drug-induced decrease in the cellular level of gamma chain mRNA. In
      addition, THC treatment decreased the 125I-labeled IL2 internalization under high
      affinity binding conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7636715
TI  - Strain-dependent drug effects in rat middle cerebral artery occlusion model of
      stroke.
AB  - In the rat middle cerebral artery occlusion (MCAO) model of embolic stroke,
      calcium antagonists, as well as competitive and noncompetitive N-methyl-D
      aspartate (NMDA) antagonists have been studied extensively by various groups.
      However, there are divergent conclusions concerning their efficiencies. These
      discrepancies may be due to the different experimental conditions and/or rat
      strains used. In this study we have assessed in five commonly used rat strains,
      under identical experimental conditions, the ability of one representative of
      each of these drug classes to reduce the infarct size in this model. Drugs or
      corresponding vehicle were injected immediately after permanent unilateral MCAO
      and the infarct volume was determined 48 hr later by magnetic resonance imaging.
      In vehicle-treated controls, the total infarct volume was strain-dependent
      (range, 70-200 microliters), primarily due to variations in the cortex. The
      extent of total infarct volume reduction (up to 65%) elicited by the three drugs
      also was strain-dependent, the main effect and variation being observed in the
      cortex (range, 0-83% reduction). No difference in efficiency was seen between the
      competitive and noncompetitive NMDA antagonist, whereas the calcium antagonist
      showed better results in all five strains. The potential to reduce the infarct
      size in the rat MCAO model with calcium or NMDA antagonists depends upon the
      strain used. The exact reasons and mechanisms are presently not understood. Such
      knowledge would certainly add to the confidence in this model and would allow
      more accurate predictions concerning the clinical efficacy of drugs in stroke
      trials.

PMID- 7636717
TI  - Comparison of the distinct effects of epidermal growth factor and betamethasone
      on the morphogenesis of the gas exchange region and differentiation of alveolar
      type II cells in lungs of fetal rhesus monkeys.
AB  - To compare the effects of epidermal growth factor (EGF) and betamethasone on the
      morphogenesis of the gas exchange region and the differentiation of the alveolar
      type II cell during fetal lung development, fetal rhesus monkeys (78% gestation)
      were treated in utero with EGF (5.33 mg/kg total dose), beta-methasone (2.6 mg/kg
      total dose) or the carrier, saline (control), every other day for 7 days. EGF
      treated monkeys had significantly increased body and adrenal weights.
      Betamethasone-treated monkeys had significantly decreased body and adrenal
      weights. Exogenous EGF reduced cytoplasmic glycogen and increased the cytoplasmic
      organelle and SP-A content within alveolar type II cells. In contrast, exogenous
      betamethasone did not alter alveolar type II cell cytodifferentiation. Neither
      EGF nor betamethasone treatment significantly altered the structure of the gas
      exchange region as shown by a lack of change from controls in alveolar airspace
      size or in the fraction of the gas exchange region that was potential airspace.
      We conclude that at clinically relevant doses, EGF greatly accelerates the
      maturation of alveolar type II cells, whereas betamethasone does not. Exogenous
      EGF may act directly on alveolar type II cells because these cells contain EGF
      receptor. Neither EGF nor betamethasone had dramatic effects on the morphogenesis
      of the gas exchange region.

PMID- 7636716
TI  - Effects of duloxetine, a combined serotonin and norepinephrine reuptake
      inhibitor, on central neural control of lower urinary tract function in the
      chloralose-anesthetized female cat.
AB  - Because all three components of lower urinary tract control (parasympathetic,
      sympathetic and somatic) are intimately associated with serotonin (5
      hydroxytryptamine [5HT])- and norepinephrine (NE)- containing terminals and
      receptors, in the present study, we examined the effects of increasing
      extracellular levels of 5HT and NE with duloxetine, a 5HT and NE reuptake
      inhibitor, on lower urinary tract function under "normal" or nonirritated
      conditions (transvesical infusion of saline) and in a model of bladder irritation
      (i.e., transvesical infusion of 0.5% acetic acid) in chloralose-anesthetized
      cats. Irritation reduced bladder capacity (to 20% of control) and produced
      insignificant increases in periurethral electromyographic (EMG) activity compared
      with nonirritated control animals. Duloxetine produced insignificant increases in
      bladder capacity and sphincter EMG activity when administered under nonirritated
      bladder conditions. However, this duloxetine "pretreatment" did prevent the
      typical acetic acid-induced reductions in bladder capacity and unmasked a marked
      activation of sphincter EMG activity on acetic acid infusion (by 8-fold).
      Furthermore, when administered initially under irritated bladder conditions,
      duloxetine produced dose-dependent increases in bladder capacity (by 5-fold) and
      increased periurethral striated muscle EMG activity (by 8-fold). The effects on
      bladder activity were due to central mechanisms since bladder contractions evoked
      by direct electrical stimulation of efferent fibers in the pelvic nerve were not
      effected by duloxetine. The effects of duloxetine on bladder capacity were
      antagonized by methiothepin, a non-selective 5HT receptor antagonist, but not by
      the other 5HT and NE receptor antagonists examined: LY53857, a 5HT2 antagonist;
      prazosin, an alpha-1-adrenergic receptor antagonist; idazoxan, an alpha-2
      adrenergic receptor antagonist; or propranolol, a beta-adrenergic receptor
      antagonist. The facilitatory effects of duloxetine on periurethral sphincter EMG
      were significantly antagonized to various degrees by methiothepin, LY53857 and
      prazosin but not by idazoxan or propranolol. These results indicate that
      duloxetine, through inhibition of 5HT and NE reuptake, has weak effects under
      normal conditions. However, under conditions of bladder irritation, duloxetine
      suppresses bladder activity through 5HT receptor mechanisms and enhances external
      urethral sphincter activity through 5HT2 and alpha-1-adrenergic mechanisms.

PMID- 7636718
TI  - Efaroxan acts peripherally to block the antisecretory and gastroprotective
      effects of moxonidine in rats.
AB  - I1-imidazoline receptor activation by moxonidine has potent antigastric secretory
      and gastroprotective effects in rats. We therefore tested whether an imidazoline
      receptor antagonist, efaroxan, would influence gastric secretion and block the
      antisecretory and antiulcer effects of moxonidine. When given
      intracerebroventricularly (i.c.v.), moxonidine inhibited basal acid output in
      conscious rats to a maximum of 38%. Moxonidine given i.p. also significantly
      increased gastric adherent mucus levels in rats subjected to cold-restraint
      stress. Efaroxan alone given i.c.v., did not influence gastric secretion nor did
      it affect moxonidine's ability to decrease gastric secretion. Similarly,
      peripherally administered efaroxan did not block the antisecretory effect of
      moxonidine given i.c.v. However, when both compounds were given i.p., efaroxan
      pretreatment at all but the lowest doses significantly blocked the antigastric
      secretory effect of moxonidine. Efaroxan alone (i.p.) did not influence stress
      induced gastric mucosal injury or adherent mucus levels. However, pretreatment of
      rats with efaroxan i.p. significantly blocked the mucus-preserving effect of i.p.
      moxonidine. These results demonstrate that central (i.c.v.) or peripheral (i.p.)
      administration of the I1-imidazoline receptor agonist moxonidine is associated
      with gastroprotection. The ability of i.p. efaroxan to block the effects of i.p.
      moxonidine but not i.c.v. moxonidine indicates that imidazoline receptors located
      centrally and peripherally may represent two unique sites associated with
      gastroprotection.

PMID- 7636719
TI  - Ameliorative effects of tea catechins on active oxygen-related nerve cell
      injuries.
AB  - Active oxygen species are suggested to be concerned with various senile
      disorders. Tea catechins, (+)catechin (CA), (-)epicatechin (EC) and (
      )epigallocatechin gallate, are polyhydroxy-fravan derivatives from tea leaves and
      have been proposed to possess active oxygen scavenging effect. Tea catechins
      protected the cultured newborn-mouse cerebral nerve cells from death induced by
      glucose oxidase. The protective potency of (-)epigallocatechin gallate was weaker
      than those of EC and CA. Learning ability of mice was assessed by a step-down
      type passive avoidance test, and memory impairment of mice was achieved by
      intracisternal injection of glucose oxidase or cerebral ischemia induced by 10
      min occlusion of the common carotid arteries. Intracisternal injection of EC
      improved the memory impairment induced by intracisternal glucose oxidase, and
      i.v. injection of CA or EC improved that induced by the cerebral ischemia. CA and
      EC depressed carrageenin-induced edema in rat hind paw, but (-)epigallocatechin
      gallate did not. These results suggest that tea catechins ameliorate the injuries
      or impairments induced by active oxygens through scavenging intracellular active
      oxygens, and might become useful for protecting human from senile disorders such
      as dementia.

PMID- 7636720
TI  - Dopamine D3-preferring ligands act at synthesis modulating autoreceptors.
AB  - Several compounds exist that demonstrate a binding preference for cloned dopamine
      D3 receptors vs. D2 receptors, including (+/-)7-OH DPAT, (+)-UH232 and (+)-AJ76.
      Inasmuch as recent evidence suggests that the dopamine D3 receptor may function
      as a dopamine autoreceptor, we have investigated the ability of these D3
      preferring ligands to act at synthesis modulating dopamine autoreceptors using
      the gamma-butyro-lactone model in vivo to isolate the presynaptic effects of (+/
      )7-OH DPAT, (+)-UH232 and (+)-AJ76. Further, given the discrete anatomical
      distribution of the D3 receptor, the striatum, n. Accumbens, and olfactory
      tubercles were examined for comparative analyses. (+/-)7-OH DPAT displayed
      agonist characteristics at synthesis modulating dopamine autoreceptors with a
      greater potency in the olfactory tubercle vs. either the striatum or the nucleus
      accumbens (ED-50 values were 31.8, 38.1 and 10.2 micrograms/kg for the striatum,
      nucleus accumbens and olfactory tubercles, respectively). Further, (+)-UH232 and
      (+)-AJ76 attenuated the effects of (+/-)7-OH DPAT (60 micrograms/kg s.c.) in all
      three regions examined. However, the effects of (+/-)7-OH DPAT were antagonized
      to a lesser extent in the olfactory tubercles than in either the striatum or the
      nucleus accumbens. Given the relative abundance of D3 receptors in the olfactory
      tubercles, the data are consistent with the notion that (+/-)7-OH DPAT may exert
      its autoreceptor effects preferentially through dopamine D3 receptors.

PMID- 7636721
TI  - Amphetamine levels in brain microdialysate, caudate/putamen, substantia nigra and
      plasma after dosage that produces either behavioral or neurotoxic effects.
AB  - Extracellular levels of d-amphetamine (AMPH) in caudate/putamen were determined
      using microdialysis and HPLC quantitation after s.c. doses that produced
      increased motor activity (1 mg/kg), stereotypic behavior (2.5 mg/kg) or dopamine
      depletion in the caudate/putamen (4 x 5 mg/kg). In 6-mo-old rats exposed to
      neurotoxic doses of AMPH sulfate (4 x 5 mg/kg in a 23 degrees C environment),
      extracellular caudate/putamen AMPH rose to levels of 7.9 +/- 0.9 microM after the
      first dose and peaked at 15.1 +/- 2.5 microM after the third dose with no further
      increases after the fourth dose. After one or three doses of 5 mg/kg, peak plasma
      and tissue levels of AMPH were 1.7 +/- 0.2 and 2.9 +/- 0.3 microM in plasma, 36
      +/- 6 and 73 +/- 10 in substantia nigra and 25 +/- 4 and 50 +/- 8 in
      caudate/putamen, respectively. Caudate/putamen extracellular AMPH levels were
      about three times higher (in either 6- or 12-mo-old rats) after 4 x 15 mg/kg in a
      10 degrees C environment and tissue levels in caudate/putamen and substantia
      nigra were three to five times higher after three doses of AMPH. However, these
      higher levels did not produce dopamine depletion in the caudate/putamen, while
      the lower doses (4 x 5 mg/kg) given at 23 degrees C did. Estimated
      caudate/putamen extracellular AMPH levels of 2.5 to 5 microM after single doses
      (1 and 2.5 mg/kg) that caused hyperactivity and stereotypic behavior are
      compatible with the 2 to 10 microM AMPH concentrations reported to be necessary
      to produce pronounced dopamine release in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7636722
TI  - Nitric oxide formation during the cytochrome P-450-dependent reductive metabolism
      of 18-nitro-oxyandrostenedione.
AB  - 18-Nitro-oxyandrostenedione (18-ONO2A), a potential mechanism-based inhibitor of
      the last steps of aldosterone biosynthesis, is well recognized by different
      cytochrome P-450s, which are able to metabolize it reductively into nitric oxide
      (NO) and 18-hydroxyandrostenedione. Rat liver microsomal P-450s are able to carry
      out this reaction with increased efficiency under anaerobic conditions. P-450 3A
      isozymes induced upon treatment of rats with dexamethasone or troleandomycin were
      best able to bind and metabolize 18-ONO2A. This reaction was shown to occur in
      the presence of dioxygen as well, suggesting that it may be of physiological
      relevance. The formation of NO was detected as a transient P-450-Fe(II)NO complex
      by UV-visible and EPR spectroscopy. In addition, steroidogenic tissues containing
      cytochrome P-450s such as bovine adrenal mitochondria or human placental
      microsomes also were capable of binding and metabolizing 18-ONO2A as judged by
      the formation of an Fe(II)NO complex. This recognition of a steroid nitrate, a
      potential antialdosterone and its subsequent metabolism under reductive
      conditions to generate NO both in hepatic and steroidogenic tissues, can be of
      pharmacological interest, because NO has been demonstrated to modulate
      steroidogenesis in addition to other processes such as vascular relaxation,
      neurotransmission or cytostasis. A nitrate derivative of a steroid could perhaps
      act as a vectorized NO precursor in which the steroid moiety is targeted
      specifically to steroid receptors or steroidogenic tissues, thus leading to
      localized NO liberation.

PMID- 7636723
TI  - Cisapride and structural analogs selectively enhance 5-hydroxytryptamine (5-HT)
      induced purinergic neurotransmission in the guinea pig proximal colon.
AB  - In the guinea pig proximal colon, 5-hydroxytryptamine (5-HT) stimulates neuronal
      5-HT1-like receptors to induce relaxations that are mediated by nitric oxide and
      ATP. In the current study, the effects of cisapride and structural analogs on
      these 5-HT-induced relaxations were investigated. In the continuous presence of
      ketanserin (0.3 microM) and tropisetron (3 microM) to block contractions via 5
      HT2A, 5-HT3 and 5-HT4 receptors, 5-HT induced relaxations that yielded a biphasic
      concentration-response curve. Cisapride (0.1-1 microM) enhanced the second phase
      of the concentration-response curve to 5-HT by about 20% to 40%, whereas from 0.3
      microM onwards, it inhibited the first phase. Also in the presence of cisapride
      (0.3 microM), tetrodotoxin (0.3 microM) abolished the relaxations to 5-HT.
      Cisapride (0.3 microM) did not affect the concentration-response curves to
      isoprenaline, nitroglycerin, nitroprusside or exogenous ATP, which demonstrated
      its specificity. The 5-HT relaxation-enhancing effects of cisapride were not
      mimicked by phentolamine (1 microM), NAN-190 (0.03 microM), spiperone (1 microM),
      citalopram (0.3 microM), paroxetine (0.3 microM), pargyline (100 microM) or SDZ
      205-557 (0.3 microM). In the presence of the inhibitor of nitric oxide synthesis,
      NG-nitro-L-arginine (100 microM), cisapride (0.3 microM) still enhanced the
      remaining relaxations to 5-HT (2-3-fold). However, in the presence of the P2
      purinoceptor antagonist suramin (300 microM), cisapride did not enhance the
      relaxations to 5-HT. In the presence of NG-nitro-L-arginine, the cisapride
      enhanced relaxations to 5-HT were inhibited by about 90% by suramin. We conclude
      that in the guinea pig colon, cisapride selectively facilitates the suramin
      sensitive, ATP-mediated part of the relaxation to 5-HT via an unidentified effect
      on intramural nerves.

PMID- 7636724
TI  - Effects of phenamil on potassium and calcium channels of guinea pig ventricular
      myocytes.
AB  - Phenamil, a phenyl-substituted amiloride derivative and a potent inhibitor of
      epithelial-type sodium channels, produces significant prolongation of the action
      potential in isolated ventricular preparations, a tissue in which epithelial-type
      sodium channels have not been reported. Experiments were therefore carried out to
      examine the possible electrophysiological effects of phenamil on whole-cell ionic
      currents recorded in voltage-clamped guinea pig ventricular myocytes. At higher
      concentrations than those required to inhibit the epithelial sodium channels,
      phenamil (10-60 microM as compared to nanomoles for epithelial sodium channels)
      significantly increased the action potential duration in ventricular myocytes. It
      also induced a slow progressive depolarization which was followed eventually by
      oscillatory potentials near -35 mV. Higher concentrations of phenamil accelerated
      these changes. These effects were partially reversible. Voltage-clamp experiments
      using slow voltage ramps from -140 mV to +60 mV or step protocols from -120 mV to
      +30 mV revealed a prominent (approximately 70% at -120 mV) inhibitory effect of
      phenamil (50 microM) on the inwardly rectifying potassium current. Phenamil (50
      microM) had little effect on the delayed rectifier potassium currents recorded by
      using long (5 sec) voltage steps from -40 mV to +60 mV. In the absence of K+,
      calcium current (L-type) was not affected by phenamil at concentrations up to 100
      microM. Our data support the concept that phenamil-induced action potential
      prolongation in guinea pig cardiac myocytes may be produced by inhibition of
      inwardly rectifying potassium current.

PMID- 7636725
TI  - Effects of N-methyl-D-aspartate antagonists in rats discriminating different
      doses of cocaine: comparison with direct and indirect dopamine agonists.
AB  - Dose-response functions for selected N-methyl-D-aspartate (NMDA) antagonists and
      direct and indirect dopamine agonists were compared in rats trained to
      discriminate either a low (2 mg/kg) or a high (10 mg/kg) dose of cocaine from
      vehicle. The NMDA-associated ion channel blockers, dizocilpine, phencyclidine and
      MgCl2, substituted fully for cocaine (> or = 90% cocaine-appropriate responses)
      in the majority of subjects under the low-dose training condition, but showed
      little or no substitution for cocaine under the high-dose training condition. The
      competitive NMDA antagonist [2R,4R,5S-(2-amino-4,5-(1,2-cyclohexyl)-7
      phosphonoheptanoic acid)] did not substitute for cocaine under either training
      condition. Cocaine, 1-(2-[bis(4-fluorophenyl)methoxyl)-4-(3
      phenylpropyl)piperazine, (+)-amphetamine and the D1 receptor agonist SKF 77434
      engendered full substitution for cocaine under both training conditions. Dose
      response functions for all four drugs were displaced to the left and average ED50
      values were reduced by 3-fold or more under the low-dose compared to the high
      dose training condition. The nonselective DA receptor agonist (-)-apomorphine
      substituted substantially for cocaine only under the low-dose training condition,
      whereas the D2 receptor agonist (+)-4-propyl-9-hydroxynapthoxazine substituted
      similarly for cocaine under both training conditions. The results show that
      change in the training dose of cocaine can affect both the shape and position of
      the dose-response functions for representative NMDA-associated ion channel
      blockers and direct and indirect dopamine agonists. The findings further show
      that under low-dose training conditions, NMDA-associated ion channel blockers can
      engender cocaine-like stimulus effects comparable to those of direct and indirect
      dopamine agonists.

PMID- 7636726
TI  - Synthetic omega-conopeptides applied to the site of nerve injury suppress
      neuropathic pains in rats.
AB  - In patients and animals with painful peripheral neuropathies, spontaneous ectopic
      discharge from injured primary afferents is hypothesized to maintain a central
      state of hyperexcitability that underlies hyperalgesia and allodynia. Temporary
      suppression of this discharge allows the central state to normalize, such that
      hyperalgesia and allodynia are absent or reduced until the resumption of the
      discharge rekindles central hyperexcitability. Previous work suggests that Ca++
      channels are involved in the genesis of spontaneous discharge from injured
      afferents. We applied SNX-111 and SNX-124 (0.1-3.0 micrograms), synthetic
      homologs of omega-conopeptides (MVIIA and GVIA, respectively) and potent blockers
      of neuronal N-type voltage-sensitive Ca++ channels, to the site of nerve injury
      via chronically implanted perineural cannulae in rats with an experimental
      painful peripheral neuropathy (the chronic constriction injury model). Heat
      hyperalgesia and mechano-allodynia were reduced for at least 3 hr. Drug
      application to a normal nerve had no effect on responses to heat or mechanical
      stimuli. These results suggest that N-type Ca++ channel blockers may be useful in
      the treatment of the abnormal pains that occur after nerve injury.

PMID- 7636727
TI  - Rifampicin induction of lidocaine metabolism in cultured human hepatocytes.
AB  - In our laboratory, cultured human hepatocytes are being evaluated as an
      experimental system to study drug interactions. We report the effect of a known
      cytochrome P450 (CYP) inducer, rifampicin, on the metabolism of lidocaine by
      primary human hepatocytes. Rifampicin has been shown to induce CYP3A4, a major
      human hepatic CYP isozyme that is known to metabolize lidocaine to its primary
      metabolite, monoethylglycinexylidide. Human hepatocytes were cultured on collagen
      coated plates in serum-free, hormone-supplemented Waymouth medium for a 3-day
      period before they were treated with rifampicin at 50 microM for 1 to 3 days.
      Hepatocytes isolated from five individuals were studied, and, in all cases,
      lidocaine metabolism was found to be induced by rifampicin, as demonstrated by a
      higher rate of monoethylglycinexylidide formation than concurrent controls. For
      three of the hepatocyte cultures, lidocaine metabolism was evaluated at various
      times after treatment. Induction was observed at 1 day after treatment, and
      reached higher levels at day 2 or 3. The level of induction was found to be
      approximately 100% for two hepatocyte isolations and approximately 600% for one
      isolation. In a separate experiment, hepatocytes were treated with rifampicin for
      a 2-day period. Rate of lidocaine metabolism at multiple substrate concentrations
      (10-120 microM) were then studied. Rifampicin induction of lidocaine metabolism
      (approximately 100%) was observed at all the lidocaine concentrations studied.
      Lineweaver-Burk plot of the data showed an increase in Vmax and a less
      significant change in Km. Induction of lidocaine metabolism by rifampicin
      (concentrations of 0.1-50 microM) was found to be dose-dependent, with
      significant induction observed at 1 microM and higher concentrations. (ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7636728
TI  - Characterization of ORG 20241, a combined phosphodiesterase IV/III cyclic
      nucleotide phosphodiesterase inhibitor for asthma.
AB  - The pharmacological profile of a novel cyclic nucleotide phosphodiesterase (PDE)
      inhibitor, Org 20241, has been characterized. The compound selectively inhibits
      PDE IV (pIC50, 5.2-6.1) and PDE III (pIC50, 4.4-4.6) from animal and human
      tissues. Org 20241 relaxed preparations of bovine trachea (pD2, 5.9 and 5.4),
      guinea pig trachea (pD2, 6.2 and 4.9) and human bronchi (pD2, 5.3 and 4.7) for
      histamine and methacholine-induced contractions, respectively. Rolipram and Org
      20241 inhibited leukotriene B4-induced thromboxaneB2 (IC50, 0.3 and 1.4 microM,
      respectively) and H2O2 (IC50, 2.1 and 0.4 microM, respectively) production in
      guinea pig eosinophils. In phenylephrine (0.3 microM) precontracted rabbit aorta
      preparations, the PDE III inhibitor Org 9935 (pD2, 6.3 and 6.1 in the presence
      and absence of endothelium, respectively) was the most effective relaxant,
      whereas Org 20241 (pD2, 5.3 and 5.4 in the presence and absence of endothelium,
      respectively) was more effective than rolipram (pD2, 4.6 and 4.1 in the presence
      and absence of endothelium, respectively). Org 20241 relaxed rabbit aorta
      preparations and airway preparations at similar concentrations. In electrically
      stimulated rabbit cardiac papillary muscles, Org 20241 had little effect on
      contractility at concentrations up to 30 microM. Lower concentrations (10 microM)
      potentiated the inotropic effect of Org 9935. Whereas the PDE III inhibitor
      milrinone (1-100 microM) enhanced the rate of repolarization of guinea pig
      papillary muscles and shortened the effective refractory period, Org 20241 and
      rolipram (1-100 microM) did not reduce the action potential duration. In the
      presence of Org 20241 or rolipram, isoproterenol did not produce a greater
      increase in the rate of repolarization or reduction in the effective refractory
      period than in the absence of these PDE inhibitors. Org 20241 is a dual PDE
      IV/III inhibitor with some PDE IV selectively. This compound relaxes airways
      smooth muscle and inhibits eosinophil activation. The data indicate that such PDE
      IV/III inhibitors may be effective for the long-term therapy of asthma.

PMID- 7636729
TI  - Involvement of dopamine, N-methyl-D-aspartate and sigma receptor mechanisms in
      methamphetamine-induced anticipatory activity rhythm in rats.
AB  - Daily injection of methamphetamine (MAP) increased the locomotor activity and
      produced the development of MAP-induced anticipatory activity on the next
      withdrawal day. Daily restricted feeding also causes a feeding-associated
      anticipatory activity rhythm. The importance of catecholaminergic neurons has
      been suggested in the manifestation of a feeding-associated corticosterone
      rhythm. In our study, we examined the role of dopaminergic neurons in the
      development of MAP-induced anticipatory activity. The development of MAP-induced
      anticipatory activity was blocked by coadministration of dopamine D2 receptor
      antagonists such as YM-09151-2 and sulpiride, the D1 receptor antagonist SCH23390
      and haloperidol weak D1/D2 receptor antagonist, but not by clozapine. The
      anticipatory activity increase was reproduced by daily injection of the D2
      receptor agonist quinpirole as well as moderately by the D1 receptor agonist
      SKF38393. Moreover, MAP-induced anticipation was blocked by coadministration of
      the N-methyl-D-aspartate receptor antagonist MK-801 or sigma ligands rimcazol and
      NE-100. Our results suggest that activation of the dopaminergic system,
      especially via D2 receptors may be required for the development of MAP-associated
      anticipatory activity increases and that N-methyl-D-aspartate receptors and sigma
      receptor mechanisms are also involved in the development of this behavior.

PMID- 7636730
TI  - Enhancement of tobramycin binding to rat renal brush border membrane by
      vancomycin.
AB  - Effects of vancomycin (VCM) on tobramycin (TOB) binding to rat renal brush border
      membrane were examined by using isolated brush border membrane vesicles. The
      binding of TOB to the membrane vesicle was enhanced by the preincubation of the
      vesicle with VCM. The Scatchard analysis showed that this enhancement was due
      mainly to the increase in the number of binding sites. D-Glucose uptake was not
      affected by VCM, which suggests that the vesicles were not damaged by VCM. The
      binding of spermine, a typical polycationic compound, to the membrane vesicles
      also was increased by VCM treatment, and this also was because of the increase in
      the number of binding sites. These results suggested that the enhanced binding of
      these cationic compounds by VCM was due to the change in the negative charge on
      the membrane surface. Considering that the binding of aminoglycosides to brush
      border membranes is the initial step for the renal accumulation followed by the
      aminoglycosides-induced nephrotoxicity, this enhancement of TOB binding to the
      membrane by VCM may be one of the reasons for the enhanced TOB nephrotoxicity by
      VCM, which has often been reported in experimental animals and patients.

PMID- 7636731
TI  - Modification of mu-opioid agonist-induced locomotor activity and development of
      morphine dependence by diabetes.
AB  - We examined the locomotor-enhancing action of mu-opioid receptor agonists, such
      as morphine and [D-Ala2, N-MePhe4, Gly-ol5]enkephalin (DAMGO), and physical
      dependence on morphine in diabetic and nondiabetic mice. Morphine (5-20 mg/kg,
      s.c.) and DAMGO (1-4 nmol, i.c.v.) had a dose-dependent locomotor-enhancing
      effect in both nondiabetic and diabetic mice. The locomotor-enhancing effects of
      morphine and DAMGO were significantly less in diabetic mice than in nondiabetic
      mice, and were significantly reduced after pretreatment with either beta
      funaltrexamine (20 mg/kg, s.c.), a selective mu-opioid receptor antagonist, or
      naloxonazine (35 mg/kg, s.c.), a selective mu1-opioid receptor antagonist. Both
      diabetic and nondiabetic mice were chronically treated with morphine (8-45 mg/kg,
      s.c.) for 5 days. During this treatment, neither diabetic nor nondiabetic mice
      showed any signs of toxicity. After morphine treatment, withdrawal was
      precipitated by injection of naloxone (0.3-10 mg/kg, s.c.). Several withdrawal
      signs, such as weight loss, diarrhea, ptosis, jumping and body shakes, were
      observed after naloxone challenge in morphine-dependent nondiabetic mice.
      Although morphine-dependent diabetic mice showed greater weight loss than
      nondiabetic mice, the incidence of jumping and body shakes after naloxone
      challenge in diabetic mice were lower than that in nondiabetic mice. These
      results suggest that diabetic mice are selectively hyporesponsive to mu1-opioid
      receptor-mediated locomotor enhancement. Furthermore, diabetes may affect mu1
      opioid receptor-mediated naloxone-precipitated signs of withdrawal from physical
      dependence on morphine.

PMID- 7636732
TI  - The effect of cocaine and other local anesthetics on central dopaminergic
      neurotransmission.
AB  - The effects of cocaine on dopaminergic function in the rat were compared with
      those of other local anesthetics having an esteratic linkage (dimethocaine,
      procaine) or an amide linkage (lidocaine). By means of reverse-phase HPLC with
      electrochemical detection and gas chromatography-mass spectrometry, levels of
      dopamine (DA) and its metabolites 3-methoxytyramine (3-MT) and
      dihydroxyphenylacetic acid were quantified in the striatum, nucleus accumbens and
      prefrontal cortex after i.p. injection of the drugs or saline. Time course and
      dose response studies determined the effects of the drugs on these parameters of
      dopaminergic function. These studies provide strong evidence that the three
      esteratic local anesthetics cocaine, dimethocaine and procaine all increase the
      synaptic presence of DA, as reflected in increased levels of 3-MT and the ratio
      of 3-MT to DA, in the striatum, nucleus accumbens and prefrontal cortex.
      Surprisingly, procaine had an equal or greater effect than cocaine and
      dimethocaine on 3-MT levels and the ratio 3-MT/DA. The effects of these drugs on
      dihydroxyphenylacetic acid, an indicator of intraneuronal metabolism of DA, were
      more variable. However, the amidergic local anesthetic lidocaine did not affect
      DA metabolism. Although the exact mechanisms behind the dopaminergic activities
      of procaine and dimethocaine remain unknown, it is clear that these drugs, as
      well as cocaine, activate dopaminergic systems in the intact animal.

PMID- 7636733
TI  - Blockade of a resting potassium channel and modulation of synaptic transmission
      by ecstasy in the hippocampus.
AB  - 3,4-Methylenedioxymethamphetamine (ecstasy, MDMA) and related amphetamines are
      CNS stimulants that have euphoric, memory-enhancing and neurotoxic properties.
      When applied in pharmacological doses to cultured rat hippocampal neurons,
      ecstasy reduced the conductance of a 50-pS barium-sensitive resting K+ channel
      and increased neuronal excitability. Ecstasy enhanced synaptic strength by
      irreversibly increasing the amplitude of excitatory autaptic currents and the
      frequency of spontaneous excitatory postsynaptic currents. Ecstasy did not alter
      the amplitude of inhibitory autaptic currents or the frequency of spontaneous
      inhibitory postsynaptic currents but reversibly prolonged the decay phase of
      inhibitory autaptic currents and spontaneous inhibitory postsynaptic currents.
      These results suggest that K+ channel blockade and the effects on synaptic
      transmission may contribute to the pharmacological effects of ecstasy and other
      amphetamines.

PMID- 7636734
TI  - Acute administration of 17 beta-estradiol inhibits calcium currents in isolated
      guinea pig detrusor myocytes.
AB  - The acute effects of 17 beta-estradiol on bladder contractile function and on
      calcium currents were evaluated in vitro on isolated guinea pig bladder strips
      and detrusor myocytes, respectively. In the isolated bladder strip, 17 beta
      estradiol inhibited KCl-induced contractions with an IC50 of 1.7 +/- 0.3 microM.
      In isolated detrusor myocytes, single cell capacitance was 52.9 +/- 2.2 pF. This
      corresponded to a mean cell surface area of 5297.5 +/- 214.8 micron2. The
      specific membrane resistance was 97.8 +/- 31.6 K omega cm2. The effects of 17
      beta-estradiol (0.1 to 3 microM) on peak transmembrane calcium currents were
      evaluated using the whole cell voltage clamp technique. Peak calcium currents
      were decreased by approximately 50% (427.8 +/- 57.6 to 226.1 +/- 70.2 pA) at 1.0
      microM. Additional analyses were performed at 1.0 microM. Evaluation of the
      current voltage relationship indicated a decrease in the maximum conductance from
      12.31 +/- 1.85 to 7.29 +/- 1.91 nS. Current activations were reasonably fit to a
      Boltzmann logistic. After exposure to 17 beta-estradiol, the activation curve was
      shifted to the right by approximately 13 mV. The voltage-dependence of calcium
      current inactivation was U-shaped, but well described by a Boltzmann relation at
      membrane potentials between -80 and 0 mV. 17 beta-Estradiol had no effect on the
      voltage-dependence of calcium current inactivation. The combination of effects on
      peak current amplitude and voltage dependence of current activation produced a
      significant decrease in the calcium "window current." Quasi steady-state ramp
      currents were characteristically "N-shaped," and after exposure to 17 beta
      estradiol became flattened.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7636735
TI  - Cold water swim stress- and delta-2 opioid-induced analgesia are modulated by
      spinal gamma-aminobutyric acidA receptors.
AB  - Cold water swim stress for 3 min at 5 degrees C produces antinociception in the
      tail-flick test in mice by activation of delta opioid receptors in the brain.
      Also, the inhibition of the tail-flick reflex produced by i.c.v. administration
      of delta opioid receptor agonists is known to be mediated by spinal gamma
      aminobutyric acid (GABA) receptors. The purpose of this investigation was to
      determine if the cold water swim stress-induced antinociceptive response is
      mediated by GABA receptors in the spinal cord. First, i.c.v. administration of
      the delta-2 receptor antagonist, naltriben, but not the delta-1 receptor
      antagonist, 7-benzylidenenaltrexone, antagonized the cold water swim stress
      induced antinociception in ICR mice and confirmed the role of delta-2 receptors
      in this response. Next, the involvement of spinal GABAA receptors was shown
      through intrathecal administration of GABAA receptor antagonists, picrotoxin and
      bicuculline, which inhibited the cold water swim stress-induced antinociceptive
      response. Thus, the antinociception produced through activation of the delta-2
      receptor in the brain by cold water swim stress involved a descending pathway
      mediated by spinal GABAA receptors. This descending pathway appeared to be the
      same as that activated by i.c.v. administration of delta-2 opioid agonists in the
      brain.

PMID- 7636736
TI  - Ritanserin, a 5-HT2A/2C antagonist, reverses direct dopamine agonist-induced
      inhibition of midbrain dopamine neurons.
AB  - Ritanserin (RIT), widely-used as a selective 5-HT2A/2C receptor antagonist, has
      been reported to produce significant therapeutic effects on the negative symptoms
      of schizophrenia and to improve extrapyramidal side effects induced by
      neuroleptics. Because midbrain dopamine (DA) systems are believed to be the major
      site of action for many antipsychotic drugs, the effect of RIT on substantia
      nigra DA neurons was examined in chloral hydrate-anesthetized rats using single
      unit recording techniques. Systemic injection of RIT (0.1-6.4 mg/kg, i.v.) had no
      consistent effect on basal firing rate but significantly reversed the inhibition
      induced by both direct and indirect DA agonists. However, our data suggest that
      this effect of RIT is largely mediated by a mechanism independent of 5-HT. Thus
      the 5-HT2A/2C agonist 1(2,5 dimethyoxy-4-iodophenyl)-2-aminopropane showed no
      effect on either basal firing rate or the inhibition induced by the direct DA
      agonist quinpirole. Neither the selective 5-HT2A antagonist MDL 100907 nor
      depletion of endogenous 5-HT using p-chlorophenylalanine mimicked the effect of
      RIT (i.e., attenuated quinpirole-induced inhibition). Furthermore, the effect of
      RIT persisted in animals pretreated with p-chlorophenylalanine. Because RIT is
      known to bind D2-like receptors and because the inhibition of DA neurons induced
      by low doses of a direct DA agonist is believed to be mediated by DA
      autoreceptors, these results suggest that RIT may act on DA autoreceptors
      directly as a DA antagonist. Since similar doses of RIT were reported to have no
      significant effect on postsynaptic D2 receptors in the striatum, it is possible
      that RIT at the doses used may selectively block DA autoreceptors.

PMID- 7636737
TI  - Agmatine, an endogenous imidazoline receptor agonist, increases gastric secretion
      and worsens experimental gastric mucosal injury in rats.
AB  - The present experiments tested the actions of a putative endogenous imidazoline
      receptor agonist, agmatine, on gastric secretion and on experimental gastric
      mucosal injury in rats. Agmatine, given i.p. (0.5-20.0 mg/kg) or i.c.v. (0.5-2.5
      micrograms), augmented basal gastric acid secretion in conscious rats to a
      maximum of 40% when given i.p. and 44% when given i.c.v. Agmatine also
      potentiated total secretory volume as well as gastric acid and pepsin output in
      pylorus-ligated rats. When administered before exposure to stress, agmatine
      significantly decreased gastric glandular mucus levels and exacerbated stress
      induced gastric mucosal injury. These results are in contrast to our data showing
      that an exogenous agonist of I1-imidazoline receptors, moxonidine, is a potent
      antisecretory and gastroprotective agent. A precise physiological role for
      agmatine in blood pressure regulation and in gastrointestinal function awaits
      clarification. However, it is possible that agmatine functions as an "inverse
      agonist" at central imidazoline receptors, resulting in hypertension, augmented
      gastric secretion and exacerbated gastric mucosal injury.

PMID- 7636738
TI  - Cardiovascular effects after the intracerebroventricular administration of
      peptide and nonpeptide angiotensin antagonists in Dahl salt-sensitive rats.
AB  - Cardiovascular responses after the central blockade of the brain angiotensin
      system with peptide or nonpeptide angiotensin II analogs in conscious, freely
      moving hypertensive Dahl salt-sensitive (DS/JR) rats were measured. Four-week-old
      animals were maintained on an 8% salt diet until experimentation at 7 weeks of
      age. At the time of experimentation, mean arterial pressures were 176 +/- 6 mm
      Hg. The i.c.v. administration of 20 micrograms of the peptide analog sarcosine1,
      threonine8-angiotensin II (sarthran) resulted in a significant bradycardic
      response (approximately 17% decrease in H.R. peaking at 8 min after injection)
      without a significant change in blood pressure. Central administration of the AT1
      antagonist losartan (10 micrograms) or of the AT2 antagonist PD 123319 (10
      micrograms) was without effect. The peptide and nonpeptide analogs differed in
      their ability to inhibit central angiotensin II (10 ng)-induced pressor and
      dipsogenic responses. PD 123319 (10 micrograms) had no effect on the pressor and
      dipsogenic responses, whereas losartan (10 micrograms) and sarthran (20
      micrograms) inhibited both responses for 85 +/- 17 and 29 +/- 3 min,
      respectively. The effect of preblocking either the AT1 or the AT2 receptors on
      the sarthran-induced bradycardia was also determined. Preblocking with either
      losartan (10 micrograms) or PD 123319 (10 micrograms) inhibited the bradycardic
      response by approximately 45%, which suggests that both receptor subtypes are
      involved in the central cardiovascular responses in the DS/JR rat and that,
      because it was attenuated by pure antagonists, the response to sarthran may be
      mediated by its agonist actions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7636739
TI  - The influence of protein binding on the elimination of acetazolamide by the
      isolated perfused rat kidney: evidence of albumin-mediated tubular secretion.
AB  - The impact of albumin on the renal elimination of acetazolamide, a low extraction
      ratio compound, was investigated in the isolated perfused rat kidney. Perfusion
      studies were conducted over a wide range of protein concentrations (0.25, 0.5,
      0.75, 1.0, 4.0 and 6.0 g/100 ml) and an initial drug concentration of 100
      micrograms/ml. Kidney viability was within normal limits among all treatment
      groups. Over the range of albumin levels studied, an approximate 3.4-fold
      increase in drug-free fraction effected a 2.8-fold increase in renal clearance.
      Although this finding contradicted conventional wisdom regarding extraction ratio
      and renal elimination, the results were consistent with a proposed ancillary role
      of albumin in renal tubular transport processes. An alternative clearance model
      was developed, analogous to earlier models of hepatic elimination. The
      facilitated renal clearance model utilized and validated in this investigation
      represents a composite of previously proposed theories, modified to account for
      albumin-mediated tubular secretion.

PMID- 7636740
TI  - Prediction of in vivo disposition from in vitro systems: clearance of phenytoin
      and tolbutamide using rat hepatic microsomal and hepatocyte data.
AB  - The kinetics of oxidation of phenytoin and tolbutamide were determined in freshly
      isolated hepatocytes and hepatic microsomes from male Sprague-Dawley rats.
      Similar enzyme kinetic models are applicable to the data from both in vitro
      systems; a two-site model for phenytoin with a high affinity (Km = 1-5 microM,
      based on unbound drug concentration), low capacity site and a low affinity, high
      capacity site, and a one-site model for tolbutamide. Steady-state infusion
      studies were performed to characterize the Michaelis-Menten parameters for
      phenytoin disposition in vivo, these data could also be described by a two-site
      metabolism model (Km 1.3 microM, intrinsic clearance 62 ml/min for unbound drug
      for the high affinity site). Comparison of in vivo and in vitro parameters (after
      scaling the latter parameters for either hepatocyte yield or microsomal recovery)
      showed excellent prediction of in vivo clearance of unbound drug from hepatocyte
      data (55 ml/min) but underprediction from microsomal data (17 ml/min). In
      contrast to phenytoin, the in vivo clearance of tolbutamide (1.5 ml/min for
      unbound drug) was equally well predicted by both hepatocyte (2.4 ml/min) and
      microsomal (3.1 ml/min) studies. The difference between the utility of in vitro
      systems to predict the in vivo clearance of these two drugs, which show similar
      pharmacrokinetic properties (low clearance restricted to unbound drug
      concentration in blood), may be a consequence of the particular terminal
      metabolite formed in each in vitro system.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7636741
TI  - Cholinesterase inhibitors proposed for treating dementia in Alzheimer's disease:
      selectivity toward human brain acetylcholinesterase compared with
      butyrylcholinesterase.
AB  - One consistent finding in senile dementia of the Alzheimer's type is that the
      brain has reduced ability to synthesize acetylcholine. This has been related, in
      part, to memory dysfunctions. Although a cholinergic deficit is not singularly
      responsible for symptoms of dementia, treatment strategies have been designed to
      facilitate cholinergic activity by inhibiting acetylcholinesterase (AChE). To
      minimize toxicity, however, a cholinesterase inhibitor selective for only AChE
      would be an ideal treatment. The purpose of this study was to determine the
      selectivity of physostigmine, metrifonate, methanesulfonyl fluoride and
      tetrahydroaminoacridine (tacrine) toward AChE as compared with
      butyrylcholinesterase (BChE) in human cortex. The results show that
      methanesulfonyl fluoride is selective as an inhibitor of AChE as compared with
      BChE. Physostigmine inhibited AChE more than BChE. Metrifonate was found to
      inhibit BChE more than AChE. Tetrahydroaminoacridine inhibited both enzymes in a
      complex way.

PMID- 7636742
TI  - Characterization of [3H]quinpirole binding to human dopamine D2A and D3
      receptors: effects of ions and guanine nucleotides.
AB  - The in vitro receptor binding characteristics of [3H]quinpirole to cloned human
      dopamine D2A (long isoform) and D3 receptors were investigated and compared with
      those of rat striatal dopamine receptors. [3H]Quinpirole selectively labeled the
      high-affinity state of cloned dopamine D2A and striatal D2 receptors with an
      affinity of about 4 nM. In the striatum, [3H]quinpirole bound to 70% of the
      receptors labeled by the antagonist [3H]raclopride, whereas the corresponding
      value for cloned dopamine D2A receptors was 26%. [3H]Quinpirole labeled both the
      high- and "low-"affinity states of the dopamine D3 receptor with the affinities
      of 0.6 nM (36% of the receptors) and 7.3 nM, respectively. At all three
      receptors, sodium decreased the proportion of receptors labeled by
      [3H]quinpirole, whereas its affinity for the remaining high-affinity sites was
      not changed. Further addition of guanine nucleotides completely converted the
      high-affinity binding into low. Thus, even the dopamine D3 receptor was regulated
      by sodium and guanine nucleotides. Competition studies for [3H]quinpirole and
      [3H]raclopride binding revealed that the agonists (+)-(R)-7-hydroxy-2
      dipropylaminotetralin and quinpirole, previously claimed to be highly dopamine D3
      selective (approximately 100-fold), displayed high affinity for the high-affinity
      agonist states of both dopamine D2 and D3 receptors. When these values were
      compared, instead of the apparent affinities from the one-site analysis, the
      dopamine D3-selectivities were 20-fold for (+)-(R)-7-hydroxy-2
      dipropylaminotetralin and 8-fold for quinpirole. Thus, it is of importance to
      consider both high- and low-affinity agonist states when receptor selectivities
      are evaluated.

PMID- 7636743
TI  - Epoxygenase metabolites of docosahexaenoic and eicosapentaenoic acids inhibit
      platelet aggregation at concentrations below those affecting thromboxane
      synthesis.
AB  - Docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids are the major n-3 fatty
      acids in fish oils. When either DHA or EPA is added to platelet suspensions,
      aggregation and thromboxane synthesis are both suppressed. However, when DHA or
      EPA is provided as a dietary supplement, only platelet aggregation is impaired
      during the early phase of the diet. In the present study, we examined whether
      cytochrome P-450 epoxygenase metabolites of DHA/EPA can inhibit platelet
      aggregation without affecting thromboxane synthesis. Epoxide regioisomers of DHA,
      EPA and arachidonic acid (AA) and their corresponding diol hydrolysis products
      were chemically synthesized. Aggregation and thromboxane A2 formation were
      induced in washed-platelet suspensions by addition of AA and measured by
      turbidometry and radioimmunoassay. The ranges of aggregation inhibition (IC50) by
      the families of epoxide regioisomers derived from DHA, EPA and AA were 0.7 to
      1.5, 3.2 to 5.4 and 1.0 to 4.0 microM, respectively. The IC50 values for the DHA,
      EPA and AA diol families ranged from 3.4 to 11.7, from 31 to 173 and from 16 to
      86 microM, respectively. Hydrolysis greatly reduced the capacity of EPA and AA
      epoxides, but not of DHA epoxides, to inhibit platelet aggregation. The IC50
      values of DHA, EPA and AA epoxide families for thromboxane synthesis ranged from
      6 to 100, from 10 to 100 and from 1.7 to 9.1 microM, respectively. Thus, in
      contrast to AA epoxides, all the DHA and EPA epoxides inhibited platelet
      aggregation at concentrations below those that affected thromboxane
      synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7636744
TI  - Effects of morphine and ketorolac on thermal allodynia induced by prostaglandin
      E2 and bradykinin in rhesus monkeys.
AB  - When administered s.c. in the tail, both prostaglandin E2 (PGE2; 1.58-158.0
      micrograms) and bradykinin (BK; 0.01-1.0 microgram) produced a dose-dependent
      allodynia in a warm-water tail-withdrawal assay in rhesus monkeys. PGE2 (A50 =
      5.3 +/- 0.15 microgram) was 143-fold less potent than BK (A50 = 0.037 +/- 0.012
      microgram) in producing allodynia at 42 degrees C. However, PGE2 (15.8
      micrograms) was longer acting than an equieffective dose of BK (0.1 microgram),
      and the highest dose of PGE2 (158.0 micrograms) was the only treatment to produce
      allodynia when 38 degrees C water was used as the thermal stimulus, suggesting
      that PGE2 was a more efficacious allodynic agent than BK. Morphine (0.1-3.2
      mg/kg) administered s.c. in the back completely blocked the allodynic effects of
      both BK (0.1 microgram) and PGE2 (15.8 micrograms), although morphine was more
      than twice as potent against BK (A50 = 0.26 +/- 0.085 mg/kg) than against PGE2
      (A50 = 0.65 +/- 0.14 mg/kg). The effects of morphine were antagonized by the
      opioid antagonist quadazocine (0.1 mg/kg), indicating that morphine's effects
      were mediated by opioid receptors. The nonsteroidal anti-inflammatory drug
      ketorolac (0.32-10.0 mg/kg) administered s.c. in the back completely blocked the
      allodynic effects of BK (A50 = 0.60 +/- 0.095 mg/kg) but did not alter allodynia
      induced by PGE2. The antiallodynic effects of ketorolac against BK were not
      antagonized by quadazocine (1.0 mg/kg), indicating that these effects were not
      mediated by mu or kappa opioid receptors. Furthermore, relative to morphine,
      ketorolac displayed a slower onset and a longer duration of action. These
      findings suggest that the allodynic effects of BK in this procedure were mediated
      entirely by cyclooxygenase products of arachidonic acid metabolism, such as PGE2.

PMID- 7636745
TI  - Pharmacological analysis of the noradrenergic control of central sympathetic and
      somatic reflexes controlling the lower urinary tract in the anesthetized cat.
AB  - Norepinephrine (NE)-containing terminals densely innervate sympathetic
      preganglionic neurons in the intermediolateral nucleus and somatic motor neurons
      in Onuf's nucleus that project through the hypogastric and pudendal nerves,
      respectively, to innervate the lower urinary tract. In the present study, we
      pharmacologically analyzed the role of noradrenergic systems on the sympathetic
      and somatic pathways to the lower urinary tract and asked: 1) Are alpha-1, alpha
      2, or beta-adrenergic receptors tonically active along sympathetic and/or somatic
      reflex pathways? And 2) what is the net effect of increasing the extracellular
      levels of NE by administration of a NE reuptake inhibitor? To address these
      questions, we recorded evoked potentials from the central ends of the hypogastric
      and pudendal nerves in response to electrical stimulation of the pelvic and
      pudendal nerves in chloralose-anesthetized cats, and the effects of prazosin (1
      300 micrograms/kg i.v.), an alpha-1-adrenergic receptor antagonist; idazoxan (1
      300 micrograms/kg i.v.), an alpha-2-adrenergic receptor antagonist; propranolol
      (1 mg/kg i.v.), a beta-adrenergic receptor antagonist; and tomoxetine (0.003-3
      mg/kg i.v.), a selective NE reuptake inhibitor, were examined. The results
      indicate that facilitatory alpha-1-adrenergic receptors are tonically active
      along both sympathetic and somatic reflex pathways, whereas inhibitory alpha-2
      adrenergic receptors are not tonically active. The net effect of acute inhibition
      of NE reuptake along sympathetic reflex pathways is increased activation of
      inhibitory alpha-2-adrenergic receptors. Along somatic reflex pathways, increased
      activation of both facilitatory alpha-1- and inhibitory alpha-2-adrenergic
      receptors were recorded after acute NE reuptake inhibition. No role for central
      beta-adrenergic receptors was noted.

PMID- 7636746
TI  - Enteral absorption of octreotide: modulation of intestinal permeability by
      distinct carbohydrates.
AB  - Distinct carbohydrates influenced the in vitro permeation of the somatostatin
      analogue octapeptide octreotide through Caco-2 cell monolayers. Apical addition
      of 20 mM D-glucose or D-xylose resulted in a 2.3- or 3.4-fold increased
      octreotide permeation, respectively. However, supplementation with 20 mM L
      glucose or 20 mM D-fructose showed no permeation enhancement. Basolateral
      addition of D-glucose or D-xylose had no significant effect on octreotide
      permeation. Apical medium supplementation with D-glucose or D-xylose increased
      permeation of the extracellular marker [14C]polyethylene glycol 4000, indicating
      that both carbohydrates directly affected the paracellular route of octreotide
      absorption. Presence of 1 mM phlorizin decreased octreotide permeation through
      monolayers in the presence of glucose on average by 12.8%, suggesting that the
      Na(+)-dependent glucose cotransporter might be partially involved in the
      enhancement of the absorption process of octreotide. Octreotide was absorbed from
      ligated jejunal loops of rat small intestine with an absolute absorption
      efficiency of about 0.3%. Coadministration of D-glucose of D-xylose resulted in a
      2.2- or 1.9-fold increased absorption of octreotide, whereas D-fructose showed no
      effect. When the peptide was given in the presence of glucose and 1 mM phlorizin,
      a significant reduction of absorption enhancement could be observed. Phlorizin
      did not inhibit octreotide absorption, when the peptide was given in the absence
      of glucose. The data suggest that in vivo the active transepithelial flux of
      solutes such as glucose contributes to the enhancement of peptide absorption.

PMID- 7636747
TI  - Sodium channel blockers partially inhibit nicotine-stimulated 86Rb+ efflux from
      mouse brain synaptosomes.
AB  - The possible contribution of non-nicotinic cation channels to nicotine-stimulated
      86Rb+ efflux was investigated. Dendrotoxin, charybdotoxin and apamin did not
      affect nicotine-stimulated 86Rb+ efflux. Although 4-aminopyridine and tetraethyl
      ammonium completely inhibited nicotine-stimulated 86Rb+ efflux, the
      concentrations required to achieve this inhibition differed markedly from those
      required to inhibit K(+)-stimulated 86Rb+ efflux. Cs+ reduced basal 86Rb+ efflux,
      but did not affect nicotine-stimulated efflux. Tetrodotoxin completely inhibited
      veratridine-stimulated 86Rb+ efflux (IC50 = 3.4 nM) and partially inhibited
      (about 42%) nicotine-stimulated efflux (IC50 = 1.3 nM). Saxitoxin also completely
      inhibited veratridine-stimulated efflux (IC50 = 19.5 nM) and partially inhibited
      (about 47%) nicotine-stimulated efflux (IC50 = 5.4 nM). Tetrodotoxin had no
      significant effect on the EC50 for nicotine, but decreased the efflux rate and
      reduced modestly the rate of desensitization measured with prolonged exposure to
      nicotine. Tetrodotoxin (50 nM) also inhibited maximal nicotine-stimulated 86Rb+
      efflux to approximately the same extent in each of ten brain regions examined.
      Nicotine-stimulated 86Rb+ efflux measured in the presence or absence of 100 nM
      tetrodotoxin is correlated with the density of [3H]nicotine, but not
      [3H]saxitoxin, binding sites in 12 regions, suggesting that the density of
      nicotinic receptors, not the number of Na+ channels, is the rate-limiting step
      for nicotine-stimulated 86Rb+ efflux. Therefore, activation of Na+ channels
      secondary to the stimulation of nicotinic receptors seems to contribute to the
      nicotine-stimulated 86Rb+ efflux observed in mouse brain synaptosomes. In
      contrast, no evidence for K+ channel modulation of nicotine-stimulated 86Rb+
      efflux from thalamic synaptosomes was obtained.

PMID- 7636748
TI  - Analgesic response and plasma and brain extracellular fluid pharmacokinetics of
      morphine and morphine-6-beta-D-glucuronide in the rat.
AB  - The analgesic effects of subcutaneously administered morphine and morphine-6-beta
      D-glucuronide (M6G) were determined in male Sprague-Dawley rats. Morphine
      produced a dose-dependent (2.5 to 10.0 mg/kg) analgesic response as measured by
      the tail-flick test. M6G in the same doses as morphine produced a greater degree
      of analgesia with longer duration of action. The concentrations of M6G and
      morphine were determined in plasma as the protein unbound form after the use of
      an equilibrium dialysis technique and in BECF after administration of the drugs
      (10.0 mg/kg s.c.). The concentrations of morphine and M6G in BECF were determined
      by using microdialysis. The concentration of M6G in plasma and BECF at each time
      interval after its administration was much higher than morphine. The maximal
      concentrations in plasma and AUC0-infinity values for M6G were, thus,
      significantly higher for M6G than for morphine in plasma and BECF. In BECF, the
      Tmax value for M6G was lower than for morphine, but the t1/2 beta values did not
      differ. In plasma, Tmax and T1/2 values for M6G and morphine did not differ, but
      volume of distribution and total clearance values for M6G were lower than for
      morphine. It is concluded that per milligram, M6G has a much higher analgesic
      potency than morphine in the rat and these differences may be related, in part,
      to the higher levels of M6G in comparison to morphine in plasma and BECF.

PMID- 7636749
TI  - Protective role of chronic ubiquinone administration on acute cardiac oxidative
      stress.
AB  - Previous studies have shown that acute exogenous administration of coenzyme
      ubiquinone (CoQ10) can protect the heart against oxidant-mediated injury. The aim
      of this study was to investigate whether protection against cardiac oxidative
      stress could be obtained by increasing tissue levels of CoQ10, as achieved by
      chronic CoQ10 supplementation. Wistar rats were randomly divided into two groups:
      a control group given standard diet and a test group receiving diet supplemented
      with CoQ10 (5 mg/kg/day) for 4 weeks. Functional and metabolic changes induced by
      oxidative stress were investigated in isolated perfused hearts and in papillary
      muscles. Tissue concentrations of ubiquinones were significantly higher in the
      left ventricle of treated rats than in controls. H2O2 infusion (60 microM for 60
      min) induced marked alterations of both developed pressure, which decreased to 
      58.8 +/- 16.8% of base line and end-diastolic pressure which increased almost 13
      fold. These effects were reduced significantly (P < .05) in hearts from CoQ10
      supplemented rats (-13.8 +/- 2.3 and +375.0 +/- 42.5%, respectively). In the same
      hearts, cumulative release of oxidized glutathione (a specific marker of
      oxidative stress) was 450.2 +/- 69.2 nmol/g of wet weight in the control group
      and only 89.6 +/- 22.3 nmol/g of wet weight in treated hearts (P < .01). In
      papillary muscles, after 60 min of perfusion with H2O2, active tension decreased,
      largely in controls whereas it was almost unchanged in the treated group (-34.4
      +/- 7.5% of baseline vs. -0.1 +/- 0.05%, P < .05).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7636750
TI  - Effects of acute and repeated administration of antidepressant drugs on
      extracellular levels of 5-hydroxytryptamine measured in vivo.
AB  - Extracellular levels of serotonin (5-HT) and the regulation of 5-HT release by
      the 5-HT1A receptor were examined after single and repeated treatment with
      different types of antidepressant drugs: the selective 5-HT uptake inhibitor
      fluoxetine, the selective norepinephrine uptake inhibitor desipramine and the 5
      HT2A/2C/alpha 2 receptor antagonist mianserin (each at 15.0 mg/kg). Extracellular
      levels of 5-HT were measured using in vivo microdialysis in the striatum and
      hippocampus of rats anesthetized with chloral hydrate. Acute administration of
      fluoxetine transiently elevated the levels of 5-HT in the striatum and
      hippocampus; desipramine did not change 5-HT levels, and mianserin slightly
      decreased 5-HT levels in the hippocampus. Rats were administered these
      antidepressant drugs for either 1 or 14 days and studied 48 hr after the final
      injection. Repeated treatment with fluoxetine increased base-line levels of 5-HT
      in the striatum and hippocampus; repeated treatment with desipramine increased
      base-line 5-HT levels in the striatum only, and repeated treatment with mianserin
      did not alter base-line 5-HT levels. Repeated fluoxetine treatment attenuated the
      ability of the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8
      OH-DPAT) to decrease 5-HT release in both the striatum and hippocampus. Repeated
      desipramine treatment did not significantly alter the effects of 8-OH-DPAT on 5
      HT release, but there was a hint of a decreased effect in the hippocampus.
      Repeated mianserin treatment did not significantly alter the effects of 8-OH-DPAT
      on 5-HT release, but there was a hint of an increased effect in the striatum. The
      results of the present study suggest that repeated treatment with antidepressant
      drugs alters extracellular levels of 5-HT and the ability of 5-HT1A receptors to
      regulate the release of 5-HT in a regionally selective manner. These changes in
      the regulation of 5-HT release produced by antidepressant drugs may be associated
      with their therapeutic effects, because they are caused by repeated rather than
      acute treatment.

PMID- 7636751
TI  - Tubulin polymerization by paclitaxel (taxol) phosphate prodrugs after metabolic
      activation with alkaline phosphatase.
AB  - Paclitaxel (taxol) phosphate derivatives BMY46366, BMY-46489, BMS180661 and
      BMS180820 were used to determine the ability of alkaline phosphatase to convert
      these water-soluble potential prodrugs to tubulin-polymerizing metabolites (i.e.,
      paclitaxel). Compounds were treated up to 180 min with an in vitro metabolic
      activation system composed of 10% bovine alkaline phosphatase in 0.2 M tris, pH
      7.4, or in 0.2 M glycine, pH 8.8, plus 0.05 M MgCl2. Samples were tested (either
      by direct addition or after methylene chloride extraction/dimethyl-sulfoxide
      resuspension) in spectrophotometric tubulin polymerization assays utilizing
      bovine-derived microtubule protein. Pretreatment of 2'- and 7
      phosphonoxyphenylpropionate prodrugs BMS180661 and BMS180820 with alkaline
      phosphatase for 30 to 120 min yielded relative initial slopes of about 20 to 100%
      at test concentrations equimolar to paclitaxel. High-performance liquid
      chromatography/mass spectrometry of BMS180661 treated with alkaline phosphatase
      confirmed the production of paclitaxel from the prodrug. In contrast, 2'- and 7
      phosphate analogs BMY46366 and BMY46489 treated with alkaline phosphatase were
      not active in tubulin assays. None of the paclitaxel phosphate prodrugs
      polymerized tubulin in the absence of metabolic activation. The differences in
      tubulin polymerization with metabolic activation may be related both to
      accessibility of the phosphate group to the enzyme and to anionic charge effects.
      These results demonstrate that certain paclitaxel phosphate prodrugs can be
      metabolized by alkaline phosphatase to yield effective tubulin polymerization.

PMID- 7636752
TI  - ZENECA ZD6169: a novel KATP channel opener with in vivo selectivity for urinary
      bladder.
AB  - (S)-N-(4-benzoylphenyl)-3,3,3-trifluoro-2-hydroxy-2-methyl-propionamide (ZD6169)
      is a novel ATP-sensitive potassium channel opener. Bladder activity and
      selectivity after oral dosing were studied in conscious, normotensive rats and
      dogs by monitoring cystometric and cardiovascular (CV) parameters. The reference
      ATP-sensitive K+ channel opener cromakalim was also evaluated in this study.
      ZD6169 significantly reduced micturition frequency in rats (ED50 = 0.16 mg/kg),
      but its effect on CV parameters was minimal (ED20 = 30 mg/kg), yielding a
      selectivity dose ratio of 187. The duration of action was between 7 and 24 hr at
      doses of 0.3 and 3 mg/kg, but it was more than 24 hr at 10 mg/kg. The ED50 value
      for bladder activity in dogs was less than 1.0 mg/kg, and the ED20 value for CV
      activity was slightly greater than 15 mg/kg but less than 20 mg/kg; the
      selectivity ratio was greater than 15. A significant improvement in bladder
      compliance was noted in dogs with ZD6169, and the bladder activity in rats was
      blocked by i.v. glibenclamide (3 mg/kg). Cromakalim had a bladder profile similar
      to that of ZD6169 but appeared to be more selective for CV parameters. In
      conclusion, ZENECA ZD6169 is a unique ATP-sensitive K+ channel opener with in
      vivo selectivity of relaxing bladder smooth muscle. This agent has the potential
      for treating patients with urge incontinence.

PMID- 7636754
TI  - CI-1007, a dopamine partial agonist and potential antipsychotic agent. II.
      Neurophysiological and behavioral effects.
AB  - CI-1007 has been described in receptor binding and biochemical tests as a
      dopamine (DA) partial agonist that exhibits DA autoreceptor agonist effects. The
      present studies describe the profile of CI-1007 in electrophysiological and
      behavioral tests. CI-1007 inhibited the firing of substantia nigra DA neurons
      with intrinsic DA agonist activity that was less than that of the full agonists
      apomorphine and talipexole but greater than that of the weak partial agonist SDZ
      208-912. CI-1007 was more potent after intracerebroventricular versus
      intraperitoneal injection in inhibiting spontaneous locomotor activity in mice,
      indicating a central site of action. In rats, CI-1007 inhibited locomotor
      activity after i.v. and p.o. injection, but did not produce locomotor stimulation
      or induce stereotypy, indicating a lack of postsynaptic DA agonist activity. The
      relative potencies of CI-1007 for inhibiting apomorphine-stimulated behaviors
      versus spontaneous locomotor activity in rodents indicated weak postsynaptic DA
      antagonist actions, consistent with a partial agonist profile. Similar to known
      antipsychotics, CI-1007 potently inhibited Sidman avoidance responding in
      squirrel monkeys, but, in contrast to most available antipsychotics, CI-1007
      caused only mild extrapyramidal dysfunction in squirrel and cebus monkeys
      sensitized to the dystonic effects of haloperidol. These data indicate that CI
      1007 is a DA partial agonist of moderate intrinsic activity that activates brain
      DA autoreceptors, produces behavioral effects predictive of antipsychotic
      efficacy and has a low liability for induction of extrapyramidal side effects.

PMID- 7636755
TI  - Prolactin release after remoxipride by an integrated pharmacokinetic
      pharmacodynamic model with intra- and interindividual aspects.
AB  - An integrated pharmacokinetic-pharmacodynamic model is suggested for remoxipride
      and its effect on prolactin (PRL) release acting by preventing the inhibitory
      effect of dopamine D2 receptors in the anterior pituitary. The model was
      implemented to describe the time course of PRL plasma levels after administration
      of two consecutive doses of remoxipride at 5 different time intervals, 2, 8, 12,
      24 and 48 hr. The model used is an indirect response model. It consists of three
      parts: 1) the pharmacokinetics of remoxipride; 2) a physiological substance model
      for PRL, incorporating the synthesis of PRL and its release into and elimination
      from plasma; and 3) a pharmacodynamic model describing the influence of
      remoxipride on the PRL release from the pool. A linear pharmacodynamic model gave
      the best description of the time course of PRL. The limitation in the PRL release
      is the amount available in the pool, which takes 24 to 48 hr to fully restore,
      rather than a maximal effect of remoxipride. The intra- and interindividual
      variability of remoxipride as well as of the PRL response was low.

PMID- 7636753
TI  - CI-1007, a dopamine partial agonist and potential antipsychotic agent. I.
      Neurochemical effects.
AB  - The receptor binding and biochemical effects of the putative dopamine (DA)
      partial agonist CI-1007 ([R(+)-1,2,3,6-tetrahydro-4-phenyl- 1-[(3-phenyl-3
      cyclohexen-1-yl)methyl]pyridine] maleate) and potential antipsychotic were
      evaluated with a variety of biochemical methods. In receptor binding studies, CI
      1007 bound to rat striatal DA receptors exhibiting a Ki of 3 nM as assessed by
      inhibition of [3H]N-propylnorapomorphine binding. CI-1007 also exhibited high
      affinity for cloned human D2L (Ki = 25.5 nM) and D3 (Ki = 16.6 nM) receptors with
      less affinity for D4.2 receptors (Ki = 90.9 nM). The affinity for serotonin-1A (5
      HT-1A), alpha-2 adrenergic and 5-HT-2 receptors was moderate (submicromolar
      range) and slight or negligible for alpha-1, DA D1 and various other receptors.
      Unlike dopamine, the inhibition of [3H]spiperone binding was monophasic for CI
      1007 and only slightly affected by the addition of Gpp-(NH)p. In vitro CI-1007
      antagonized the forskolin-induced increases in cyclic AMP levels in GH4C1 cells
      expressing the human D2L receptor, having an intrinsic activity of 53% of that
      seen with the full agonist quinpirole. In vivo CI-1007 antagonized the gamma
      butyrolactone (GBL)-induced accumulation of L-3,4-dihydroxyphenylalanine in
      striatum and mesolimbic regions of rat brain, causing a maximal 64% reversal in
      striatum, consistent with a partial agonist profile. In microdialysis studies it
      decreased DA overflow in both striatum and nucleus accumbens, indicating
      decreased release of DA. CI-1007 also reduced brain DA synthesis (DOPA
      accumulation), metabolism (DOPAC and HVA) and utilization (after tyrosine
      hydroxylase inhibition with alpha-methyl-p-tyrosine). CI-1007 did not affect
      striatal acetylcholine levels indicating lack of potent postsynaptic DA actions.
      CI-1007 seemed to be selective for DA neurons as it did not alter rat brain
      norepinephrine (NE) synthesis in the NE-enriched brainstem or NE utilization in
      the mesolimbic region. In addition, it did not affect in general 5-HT synthesis
      and metabolism in striatum and mesolimbic regions. These neurochemical results
      demonstrate that CI-1007 is a selective potent brain dopamine partial agonist
      with limited agonist activity at postsynaptic DA receptors.

PMID- 7636756
TI  - The neurokinin1 receptor antagonist CP-99,994 reduces catalepsy produced by the
      dopamine D2 receptor antagonist raclopride: correlation with extracellular
      acetylcholine levels in striatum.
AB  - The ability of the substance P (NK1) receptor antagonist CP-99,994 to alter
      catalepsy induced by a dopamine D1 or D2 receptor antagonist and the ability of
      CP-99,994 to influence acetylcholine (ACh) release in the striatum were
      investigated in rats. Catalepsy produced by the D1 antagonist SCH 23390 (0.5
      mg/kg s.c.) was not altered by CP-99,994 (0.5, 2.5, or 10 mg/kg s.c.). In
      contrast, catalepsy induced by the D2 antagonist raclopride (2.5 mg/kg i.p.) was
      attenuated by CP-99,994 (2.5 and 10 mg/kg). CP-99,994 (10 mg/kg) did not
      stimulate locomotion when given alone. The less active enantiomer of CP-99,994,
      CP-100,263 (10 mg/kg), did not alter raclopride-induced catalepsy. Both systemic
      administration and intrastriatal perfusion of CP-99,994 alone decreased striatal
      ACh release. Bilateral intrastriatal perfusion of CP-99,994 (40 and 100 microM)
      reduced catalepsy produced by raclopride and attenuated raclopride-induced
      increases in striatal ACh release. The reductions in the duration of catalepsy
      and decreases in striatal ACh release associated with CP-99,994 perfusion were
      positively correlated. These findings suggest that blockade of striatal NK1
      receptors reduces catalepsy induced by a dopamine D2 antagonist, an effect
      mediated, at least in part, by reducing striatal ACh release. Striatal NK1
      receptors, therefore, may be a new therapeutic target for developing drugs that
      alleviate motor side effects associated with antipsychotic treatment.

PMID- 7636757
TI  - Colchicine and cytochalasin B enhance cyclic AMP accumulation via postreceptor
      actions.
AB  - The role of cytoskeletal microtubules and microfilaments in modulating cAMP
      generation in S49 lymphoma cells was investigated using the agents colchicine and
      cytochalasin B, respectively, which are known to disrupt these structures. A 1-hr
      pretreatment of S49 cells with 10 microM colchicine typically enhanced maximal
      isoproterenol-(beta-adrenergic receptor) stimulated cAMP accumulation by 100%,
      whereas cytochalasin B increased isoproterenol-stimulated cAMP by 30%. The
      combination of colchicine and cytochalasin B synergistically enhanced agonist
      stimulated cAMP to 225% over control values. A synergistic increase in cAMP
      accumulation was also observed in cells treated with the agonist prostaglandin E1
      or cholera toxin (which activates the stimulatory guanine nucleotide regulatory
      (Gs) protein). Colchicine and cytochalasin B did not ablate the inhibitory
      effects of somatostatin or the stimulatory effect of pertussis toxin treatment on
      beta-receptor-stimulated cAMP accumulation, indicating that these cytoskeletal
      disrupting agents do not enhance responsiveness in S49 cells via alterations in
      the inhibitory guanine nucleotide regulatory protein pathway. Moreover,
      colchicine, but not cytochalasin B treatment, enhances expression of
      isoproterenol-promoted 3H-forskolin binding in intact cells (a measure of
      Gs/adenylyl cyclase coupling). Thus, colchicine and cytochalasin B appear to
      enhance signaling in the Gs/adenylyl cyclase pathway by alterations of components
      distal to hormone receptors, most likely at the Gs protein and/or via cAMP
      generation. These results imply that microtubules and microfilaments can interact
      in the regulation of this pathway and that increases in cellular cAMP may
      contribute to the action of drugs that alter function of these cytoskeletal
      elements.

PMID- 7636758
TI  - Effects of sulpiride and SCH 23390 on methamphetamine-induced changes in body
      temperature and lethality.
AB  - Data from human and animal studies suggest that hyperpyrexia contributes to both
      the neurotoxic and the lethal effects of stimulant drugs such as methamphetamine
      (METH). Because many of the effects of METH involve the release of dopamine from
      CNS neurons, we examined the effects of D1 and D2 dopamine receptor antagonists
      on METH-induced lethality and determined whether these effects correlated with
      changes in body temperature. In the first set of experiments, we found that the
      D2 antagonist sulpiride (SUL; 20, 40 or 80 mg/kg) potentiated the lethality
      caused by a single injection of METH (10 mg/kg). Pretreatment with the D1
      antagonist SCH 23390 (SCH; 0.5 mg/kg) reduced the lethality induced by METH alone
      or by SUL/METH. Other D2 or 5-hydroxytryptamine antagonists prevented, rather
      than potentiated, METH-induced lethality. In a second set of experiments, rectal
      temperatures were recorded in METH-injected animals pretreated with SCH or SUL.
      METH caused a significant increase (i.e., above vehicle-injected levels) in body
      temperature at 2.5 hr after injection. The effects of SCH or SUL pretreatment on
      METH-induced changes in body temperature suggest that the lethality-potentiating
      and -protective effects of SUL and SCH, respectively, were not due to altered
      thermoregulatory responses. These data support the idea that D1 receptor
      activation is an important event in the lethality caused by METH and that SUL may
      potentiate D1 receptor activation by augmenting METH-induced DA release.

PMID- 7636759
TI  - The piglet as a suitable animal model for studying the delayed phase of cisplatin
      induced emesis.
AB  - In 46 weaned piglets we surgically implanted a cannula in the jugular vein and
      electrodes for ECG and EMG recordings. After a 4- to 5-day recovery, piglets were
      hydrated, then dosed with cisplatin (5.5 mg/kg i.v.) and recorded continuously
      for the next 60 h. Thirteen piglets (i.e., controls) received only cisplatin.
      Twenty-three other piglets received, 15 min before cisplatin, an i.v. injection
      of granisetron (0.25, 0.5, 2 or 7 mg/kg) or ondansetron (0.5, 2 or 7 mg/kg). Ten
      other piglets received, in addition to cisplatin, multiple injections of
      granisetron (1 mg/kg) and ondansetron (3.5 mg/kg). All control piglets exhibited
      both acute and delayed emesis. The first vomiting occurred with a latency of 2.13
      +/- 0.82 hr after cisplatin administration; emetic intensity reached a peak (5
      vomits/hr) within 2 hr and then decreased rapidly. No vomiting was observed
      between the 16th and 18th hr. The mean number of vomits during the first 16th was
      18.4 +/- 2. Delayed emesis started at the 18th hr and lasted until the 58th hr.
      The mean number of vomits during the whole of the delayed phase was 9.6 +/- 2.4;
      the highest emetic intensity (1.2 vomit/hr) occurred between the 21th and the
      22th hr. Pretreatment with a 5-HT3 receptor antagonist increased significantly
      the latency of the first emetic event in a dose-dependent manner. However, the
      severity of the acute phase was reduced significantly only with granisetron at
      the dose of 7 mg/kg, although the severity of the delayed phase remained
      unchanged, irrespective of the dose of granisetron. Three about five piglets
      treated repeatedly with granisetron did not vomit throughout the chemotherapy
      course. In contrast, no complete control was observed with repetitive injections
      of ondansetron. Cisplatin inducing both acute and delayed vomiting in the piglet
      without any lethality; this animal is a suitable model in which to study the
      pathogenesis of delayed emesis.

PMID- 7636760
TI  - Modulation of the GABAA receptor by propofol is independent of the gamma subunit.
AB  - Many anxiolytics, anticonvulsants and general anesthetics modulate gamma
      aminobutyric acid type A (GABAA) receptors. The anxiolytic benzodiazepines
      potentiate the actions of GABA, and this only at GABAA receptors with gamma
      subunits. The general anesthetics both potentiate GABA and activate GABAA
      receptors directly, but their binding sites on the receptor are poorly defined.
      We examined whether the gamma 2 subunit was required for the modulation of GABAA
      receptors by the general anesthetic 2,6-diisopropylphenol (propofol). Using the
      patch-clamp technique, we recorded membrane currents from HEK293 cells
      transfected with human alpha 2, beta 1 and gamma 2 cDNAs and with alpha 2 and
      beta 1 cDNAs alone. Both forms of the receptor were activated by GABA and by
      propofol at low concentrations. At maximal doses, propofol was considerably less
      effective than GABA as an activator of alpha 2 beta 1 GABAA receptors, but it had
      an efficacy similar to that of GABA as an activator of alpha 2 beta 1 gamma 2s
      receptors. In addition to activating currents directly, propofol potentiated
      currents elicited by GABA recorded from cells expressing either subunit
      combination. We conclude that the gamma 2 subunit is not a prerequisite for
      activation of GABAA receptors by propofol or for its potentiation of GABA
      activated currents. However, the subunit may contribute to the efficacy of
      propofol as a GABAA receptor activator.

PMID- 7636761
TI  - Endothelin-1 modulates cyclic GMP production and relaxation in human pulmonary
      vessels.
AB  - The aim of this study was to examine the effects of endothelin-1 (ET-1) on sodium
      nitroprusside (SNP) induced relaxation and cyclic 3',5'-guanosine monophosphate
      (cGMP) accumulation in human pulmonary vessels. The basal levels of cGMP were
      similar in arteries (2.48 +/- 0.24 pmol/mg protein; n = 7) and veins (3.25 +/-
      0.24 pmol/mg protein; n = 7). In tissues (n = 7) treated with N omega-nitro-L
      arginine and indomethacin, cGMP values were significantly reduced (arteries, 1.30
      +/- 0.24 pmol/mg protein and veins, 1.95 +/- 0.28 pmol/mg protein). In treated
      tissues, SNP (10 microM) increased the cGMP level by 10-fold in arteries and
      veins. ET-1 (0.02 and 0.2 microM) reduced significantly the cGMP increase in SNP
      stimulated vessels. This inhibition was greater in veins (76%) when compared with
      arteries (34%). Norepinephrine (10 microM) did not affect the cGMP levels. The
      sensitivity and the maximal relaxation induced by SNP in veins contracted with ET
      1 (0.2 microM) was significantly diminished (in comparison with norepinephrine;
      10 microM). In arteries, SNP relaxations were not altered by ET-1 contraction.
      Inasmuch as 8-bromo-cyclic 3',5' guanosine monophosphate curves were not altered
      by ET-1 treatment in either arteries or veins, the relaxant mechanisms that are
      downstream of guanylate cyclase activation apparently are not affected. These
      results suggest that ET-1 may play a role in the control of muscle tone in the
      human pulmonary vascular bed by modifying cGMP levels associated with
      vasorelaxant agonist stimulation.

PMID- 7636762
TI  - Human prostate muscarinic receptor subtypes.
AB  - The alpha adrenergic receptor subtypes of the human prostate have been
      intensively investigated, while the muscarinic receptor subtypes and their
      function have yet to be determined in this tissue. [3H]-QNB binding to muscarinic
      receptors was performed on membrane homogenates of adenoma from six prostatectomy
      specimens resulting in an average total receptor density of 46 fMol/mg protein.
      Pirenzepine, hexahydrosiladifenidol, and para-fluoro-hexahydrosiladifenidol,
      drugs with high affinity for the M1 subtype, were significantly more potent
      inhibitors of [3H]-QNB binding than the M2 selective drug methoctramine.
      Immunoprecipitation studies were done using antisera raised to individual M1-M5
      receptor subtypes. Approximately 75% of the solubilized receptors in the adenoma
      specimens were immunoprecipitated with the anti-M1 antibody, in contrast to 5% or
      less with antibodies against M2, M3 or M4 subtypes. These immunoprecipitation
      studies confirm the preponderance of the M1 subtype in prostate adenoma suggested
      by the high affinity pirenzepine binding. M1 receptors, when incubated with
      agonist, coimmunoprecipitated with the alpha subunits of the guanine nucleotide
      binding regulatory proteins Gi alpha, Gq/11 alpha and G16 alpha.
      Immunohistochemical staining with the anti-M1 antibody demonstrates the M1
      receptor to be localized to the glandular epithelium. The human prostate is the
      first peripheral tissue in which a preponderance of the M1 subtype of muscarinic
      receptors has been demonstrated.

PMID- 7636763
TI  - Diphenylhydantoin induces apoptotic cell death of cultured rat cerebellar granule
      neurons.
AB  - Apoptosis is one form of physiological or programmed cell death responsible for
      the selective elimination of various cell types during development. We have
      observed and characterized a delayed-type of neurotoxicity induced in cultured
      cerebellar granule neurons by diphenylhydantoin. Diphenylhydantoin toxicity of
      cerebellar granule neurons is time and concentration dependent. Morphological
      studies using Nomarski optics and staining with the fluorescent dye Hoechst 33258
      demonstrate that diphenylhydantoin-induced neurotoxicity of cerebellar granule
      neurons is associated with cytoplasmic blebbing, heterochromatic clumping and
      condensation of chromatin that precede cell death. Unlike glutamate toxicity
      (excitotoxicity) diphenylhydantoin-induced neurotoxicity of cerebellar granule
      neurons is attenuated by actinomycin D and cycloheximide, and is associated with
      nucleosomal size DNA fragmentation. Since we have previously reported that
      depolarization of cultured cerebellar granule neurons with high concentrations of
      K+ promotes the survival of these neurons by blocking apoptosis, we examined the
      effects of diphenylhydantoin on the K(+)-evoked increase in intracellular
      calcium. Using microfluorimetry and fura-2 to measure intracellular calcium we
      found that neurotoxic concentrations of diphenylhydantoin markedly reduce the
      increase in intracellular calcium associated with elevated extracellular
      potassium. Taken together, these data demonstrate that exposure of cultured
      cerebellar granule neurons to pharmacologically relevant concentrations of
      diphenylhydantoin results in a delayed type of neurotoxicity characterized by the
      biochemical and morphological features of apoptosis.

PMID- 7636764
TI  - Neuroprotective actions of 2-amino-N-(1,2-diphenylethyl)-acetamide hydrochloride
      (FPL 13950) in animal models of hypoxia and global ischemia.
AB  - 2-Amino-N-(1,2-diphenylethyl)-acetamide hydrochloride (FPL 13950) has been
      demonstrated to have good anticonvulsant efficacy and a relative lack of acute
      side effects in rodents. Similar in structure to remacemide hydrochloride, it was
      also shown to possess weak potency as an uncompetitive antagonist of N-methyl-D
      aspartic acid (NMDA) receptors. In our study FPL 13950 was profiled preclinically
      as a potential neuroprotective agent with respect to lengthening the survival
      time of rodents exposed to hypoxia, as well as for ability to protect the
      vulnerable CA1 pyramidal neurons of the rat and dog from the consequences of
      global ischemia. Under conditions of hypoxia, pretreatment of rodents with FPL
      13950 resulted in an extension in the time to loss of the righting reflex (rats)
      and mortality (rats and mice). This occurred whether the rats were maintained at
      ambient body temperature or made hyperthermic. When administered after 30 min of
      four-vessel occlusion global ischemia for periods of either 7 (b.i.d.) or 14 days
      (s.i.d.), FPL 13950 exhibited protection of the vulnerable CA1 hippocampal
      neurons in rat. In the 14-day treatment study the CA3 neurons were evaluated and
      FPL 13950 was found to prevent the lesser degree of ischemic-induced damage to
      this hippocampal region. In ischemic rats treated with FPL 13950 for 7 days,
      electrophysiological responses of CA1 neurons (orthodromic and antidromic
      population spikes, in vitro) were also preserved after FPL 13950 treatment. FPL
      13950 was administered i.v. at 30 min after 8 min of clamping the ascending aorta
      in dogs, followed by a b.i.d./s.i.d. dosing regimen for 1 wk. Neuronal damage to
      CA1 was considerable in the saline-treated ischemic animals but significantly
      protected in dogs receiving FPL 13950. FPL 13950 continues to serve as a
      potential backup candidate for remacemide HCl which is currently in clinical
      trials for patients with stroke and epilepsy.

PMID- 7636765
TI  - Two regions in the isolated brainstem of the frog that modulate respiratory
      related activity.
AB  - Using microinjection techniques, we have explored the isolated, complete midline
      sectioned brainstem of the frog (Rana catesbeiana) to identify regions that
      influence the endogenous respiratory-related motor activity. Ten-nanoliter
      injections of lidocaine (1%), GABA (100mM) and glutamate (10 and 100 mM) into
      discrete regions of the rostral and the caudal brainstem produced different
      effects on the phasic neural discharge. In the rostral site lidocaine, GABA and
      glutamate injections altered neural burst frequency with little or no effect on
      burst amplitude. In the caudal site, responses to lidocaine and GABA injections
      consisted primarily of decreases in neural burst amplitude, often, but not always
      associated with minor decreases in burst frequency. In the same region, the
      response to glutamate was characterized by a temporary interruption of the
      rhythmic neural burst activity. The largest responses to substance injection in
      both regions were obtained at sites ranging between 200 and 500 microns from the
      ventral surface, in the ventral medullary reticular formation. The results reveal
      the existence of two areas in the frog brainstem that influence respiratory motor
      output, one related to the respiratory burst frequency and the other related to
      the amplitude of the motor output.

PMID- 7636766
TI  - Selective phonotaxis to advertisement calls in the grey treefrog Hyla versicolor:
      behavioral experiments and neurophysiological correlates.
AB  - 1. The significance of particular acoustic properties of advertisement calls for
      selective phonotaxis by the gray treefrog, Hyla versicolor (= HV), was studied
      behaviorally and neurophysiologically. Most stimuli were played back at 85 dB
      SPL, a level typically measured at 1-2 m from a calling male. 2. Females
      preferred stimuli with conspecific pulse shapes at 20 degrees and 24 degrees C,
      but not at 16 degrees C. Tests with normal and time-reversed pulses indicated the
      preferences were not influenced by the minor differences in the long-term spectra
      of pulses of different shape. 3. Pulse shape and rate had synergistic or
      antagonistic effects on female preferences depending on whether the values of one
      or both of these properties in alternative stimuli were typical of those in HV or
      heterospecific (H. chrysoscelis = HC) calls. 4. More auditory neurons in the
      torus semicircularis were temporally selective to synthetic calls (90%) than to
      sinusoidally AM tones and noise (< 70%). 5. Band-pass neurons were tuned to AM
      rates of 15-60 Hz. Neurons were more likely to be tuned to HV AM rates (< 40 Hz)
      when stimuli had pulses with HV rather than HC shapes. 6. Sharp temporal tuning
      was uncommon and found only in neurons with band-pass or low-pass
      characteristics. 7. Many neurons differed significantly in response to HV and HC
      stimulus sets. Maximum spike rate was more often elicited by an HV stimulus (74%)
      than by an HC stimulus (24%). 8. Differences in spike rates elicited by HV and HC
      stimuli were attributable to combinations of differences in the rise times and
      shapes of the pulses.

PMID- 7636767
TI  - Specificity and sensitivity of the olfactory organ of the zebrafish, Danio rerio.
AB  - 1. The specificity and sensitivity of the olfactory organ of adult zebrafish,
      Danio rerio, to selected amino acid, bile acid, and steroid odorants were
      characterized using the electro-olfactogram recording technique. The olfactory
      organ was responsive to 28 of the 29 odorants tested. 2. All of the 100 microM
      amino acid and bile acid stimulants elicited a negative-going response that was
      significantly greater than the response to the artificial fresh-water control.
      The general pattern of relative stimulatory effectiveness established for the
      amino acid stimuli was neutral amino acids > basic amino acids > acidic amino
      acids > imino acids. The general pattern of relative stimulatory effectiveness of
      100 microM bile acid stimuli was taurine-conjugated bile acids > glycine
      conjugated bile acids approximately non-conjugated bile acids. The responses to
      the most stimulatory bile acid odorants were up to 40% larger than the responses
      to the most stimulatory amino acid odorants. 3. The response threshold for
      cysteine and taurocholic acid, the most stimulatory of the amino acid and bile
      acid stimuli tested, was approximately 10(-8) M. Females are significantly more
      sensitive to these odorants than males.

PMID- 7636768
TI  - What can consultation-liaison psychiatry contribute to psychosomatic research?

PMID- 7636769
TI  - Women, anger, and cardiovascular responses to stress.
AB  - Cardiovascular reactivity (CVR) to stressful stimuli is predictive of future
      development of cardiovascular disease (CVD). Anger appears to be an important
      mediator of this relationship. Unfortunately, the majority of research in this
      area has utilized predominantly male subjects, leaving the relationship between
      CVD and anger in females largely unexplored. To address the dearth of research
      among females, the present study examined the relationship between Anger-In, as
      well as Anger-Out, and CVR to stressors among women. Females reporting moderate
      levels of Anger-Out exhibited lower blood pressure reactions to a mental
      arithmetic stressor than females reporting high and low levels of Anger-Out.
      Females reporting moderate levels of Anger-Out also exhibited lower heart rate
      reactions than individuals reporting high levels of Anger-Out. Anger-In was not
      related to CVR in the present study.

PMID- 7636770
TI  - Intermenstrual affect in women with symptomatic premenstrual change.
AB  - To determine whether women seeking treatment for symptomatic premenstrual change
      have ongoing psychological disturbance, we undertook a cross-sectional,
      comparative study across four groups of reproductive-age women. Subjects were 35
      patients with symptomatic premenstrual change and no psychiatric history, 35
      women without symptomatic premenstrual change, 35 patients with affective
      disorders, and 35 women from the community at large. All women except those in
      the community sample were tested in the intermenstrual phase (after menses but
      before the 12th cycle day). Psychological tests administered were Profile of Mood
      States, State-Trait Anxiety Inventory, Institute for Personality and Ability
      Testing (IPAT) Anxiety Scale, IPAT Depression Scale, General Health Questionnaire
      and the Family Inventory of Life Events (FILE). Demographic data and information
      concerning present and past stresses were also collected. Women with symptomatic
      premenstrual change were distinguishable from psychiatric patients on assessment
      of intermenstrual mood state. They were no different from women within the
      community at large or from non-symptomatic women. When symptomatic women reported
      on time periods, which include the premenstrual phase of the cycle, we found
      results at variance with those obtained in relation to current state mood. While
      not unlike the women from the community at large in longer term affective
      characteristics, they were consistently different from non-symptomatic women and
      sometimes indistinguishable from psychiatric patients. Women with symptomatic
      premenstrual change also reported higher levels of past external stresses than
      women taken from the community at large.

PMID- 7636771
TI  - Clinical features of patients with anorexia nervosa: assessment of factors
      influencing the duration of in-patient treatment.
AB  - We investigated that factors affecting the duration of in-patient treatment of
      patients with anorexia nervosa by comparing pretreatment clinical features with
      the length of hospitalization in 55 patients. Only patients who had completed the
      entire course of treatment were included in our analysis. Longer hospitalization
      was correlated with: poor social adaptation; anxiety and/or personality disorders
      before onset; older age at onset; older age at admission to our hospital; lower
      minimum body weight after onset; lower body weight at admission; longer duration
      of illness; frequent previous hospital treatment and/or history of in-patient
      treatment for anorexia nervosa or other somatic disorders after onset; habitual
      stimulant (alcohol, coffee and/or cigarettes) abuse; and a history of stealing
      after onset. Step-wise regression analysis revealed that minimum body weight
      after onset and age at admission explained 47% of the variance in the duration of
      in-patient treatment. We also describe the nature of in patient treatment
      typically offered to patients with anorexia nervosa in Japan.

PMID- 7636772
TI  - Body image, disfigurement and disability.
AB  - The body-related attitudes of groups of women suffering from physical conditions
      that are commonly regarded as being disfiguring and/or disabling were studied by
      means of the Body Attitudes Questionnaire. Despite their conditions, the women
      did not necessarily disparage their bodies. They also seemed to worry less about
      small changes in weight and shape than did comparable women without physical
      difficulties, and to have an enhanced sense of their own robustness. There was an
      indication that development of negative body attitudes might be linked to
      emergence of a chronic physical condition during adolescence, rather than from
      birth or during adulthood. If our results are confirmed, they point to the need
      to pay special attention to the psychological needs of women whose bodies become
      dysfunctional at this sensitive time.

PMID- 7636773
TI  - Reducing anxiety during phase I cardiac rehabilitation.
AB  - Anxiety can produce undesired effects in patients recovering from cardiac
      conditions including coronary artery bypass grafting surgery. Pharmacological,
      psychological and educational interventions are used to reduce patient anxiety.
      This study compared the effects on state anxiety of participation in one of two
      Phase I (in-patient) educational interventions for patients undergoing their
      first coronary artery bypass grafting surgery. Subjects (n = 96) were randomly
      assigned to either a traditional, staff-directed intervention or an intervention
      based on a collaborative approach. Eighty subjects were included in the data
      analyses. Results demonstrated that subjects in the collaborative-based
      intervention had significantly less state anxiety at hospital discharge than
      those in the traditional intervention. The collaborative approach offered
      patients opportunities to address individually identified concerns regarding
      recovery and future functioning and to exert control over facets of their
      hospitalization experience.

PMID- 7636774
TI  - Diabetes, psychological function and male sexuality.
AB  - The aim of the study was to assess psychological contributors or correlates of
      sexual dysfunction in diabetic men. The study was conducted on 40 diabetic men
      and 40 age-matched healthy volunteers. The subjects underwent a psychosexual
      interview with their sexual partners and had a comprehensive medical evaluation
      to rule out the confounding effects of other illnesses or medications.
      Psychiatric, psychological and marital information was obtained with the Schedule
      for Affective Disorders and Schizophrenia (SADS-L), the SCL-90-R, the Derogatis
      Sexual Function Inventory, the Locke-Wallace Marital Adjustment test and the
      Dyadic Adjustment Inventory. Compared to controls, diabetic patients had
      significantly lower levels of erotic drive, sexual arousal, enjoyment and
      satisfaction. Problems in these areas coexisted with alterations in sexual
      attitudes and body image but were not related to group differences in marital
      adjustment as reported separately by the patients and their partners. There was
      no evidence that psychological distress or psychiatric disorders are associated
      with diabetes or with its effects on sexual function.

PMID- 7636775
TI  - The Multidimensional Fatigue Inventory (MFI) psychometric qualities of an
      instrument to assess fatigue.
AB  - The Multidimensional Fatigue Inventory (MFI) is a 20-item self-report instrument
      designed to measure fatigue. It covers the following dimensions: General Fatigue,
      Physical Fatigue, Mental Fatigue, Reduced Motivation and Reduced Activity. This
      new instrument was tested for its psychometric properties in cancer patients
      receiving radiotherapy, patients with the chronic fatigue syndrome, psychology
      students, medical students, army recruits and junior physicians. We determined
      the dimensional structure using confirmatory factor analyses (LISREL's unweighted
      least squares method). The hypothesized five-factor model appeared to fit the
      data in all samples tested (AGFIs > 0.93). The instrument was found to have good
      internal consistency, with an average Cronbach's alpha coefficient of 0.84.
      Construct validity was established after comparisons between and within groups,
      assuming differences in fatigue based on differences in circumstances and/or
      activity level. Convergent validity was investigated by correlating the MFI
      scales with a Visual Analogue Scale measuring fatigue (0.22 < r < 0.78). Results,
      by and large, support the validity of the MFI.

PMID- 7636776
TI  - The recognition of depression in patients referred to a consultation-liaison
      service.
AB  - The recognition of depression was examined in 987 medical and surgical patients
      referred to a consultation-liaison psychiatry service. Overall concordance of
      recognition of depression by the referring doctor and diagnosis of depression by
      the consultant psychiatrist was 74%; 41% false-positive rate, 15% false-negative
      rate. Concordance was higher in the Renal Unit and lower in the General Medical
      Unit. Patients for whom there was discordance were significantly older than those
      for whom there was concordance. Patients referred for depression but not
      diagnosed as such by psychiatrists received DSM-III-R diagnoses of Organic Mental
      Disorder, Somatoform and Related Disorders, Psychoactive Substance Use Disorders
      and Personality Disorders. On the other hand, patients diagnosed as having
      depression but not referred as such were referred instead for ill-defined reasons
      (suspected psychological component to illness, coping problems), suicide risk
      evaluation and routine pre-operative or pre-dialysis assessment. The results
      highlight the continuing misdiagnosis of psychiatric disorders, especially
      Organic Mental Disorders, as well as the mislabelling of the syndrome described
      by psychiatrists as depression. This is part of the wider problem of defining the
      boundaries of a clinical depressive syndrome in the physically ill.

PMID- 7636777
TI  - The anger recall interview and cardiovascular reactivity in women: an examination
      of context and experience.
AB  - Recent research has focused on the role of hostility as a risk factor for
      coronary heart disease. Hostility has been linked independently to cardiovascular
      mortality and, as a component of Type A behavior, to atherogenesis and myocardial
      infarction; however, the mechanisms by which hostility manifests its effects on
      the cardiovascular system have not been determined. In addition, hostility has
      been evaluated as a trait measure, with little emphasis on how anger-provoking
      episodes may be perceived by individuals. The present study seeks to evaluate the
      affective experience of hostility, through an anger recall interview, and relate
      qualities of that experience to one potential mechanism of cardiovascular risk,
      cardiovascular reactivity. Fifty-eight women, classified by structured interview
      as Type A or B, participated in an anger recall interview while their heart rate
      and blood pressure were monitored. Type A women manifested greater systolic
      reactivity when their anger was in response to frustration of autonomy needs,
      while Type B women exhibited greater heart rate reactivity in response to
      frustration of affiliation needs. All women who suppressed anger expression
      experienced higher pressor responses than women who expressed anger assertively.
      Future investigations may find the content of an interview as useful as the
      procedure itself in studies of cardiovascular reactivity.

PMID- 7636778
TI  - The effects of the opiate antagonist naloxone on measures of cellular immunity
      during rest and brief psychological stress.
AB  - This study investigated subjective, cardiovascular, and cellular immune system
      responses in 20 healthy young men during brief mental arithmetic stress compared
      with a video-watching control task. The role of endogenous opioids in mediating
      the immunological change to stress was examined by pre-task administration of the
      opiate antagonist naloxone. Immune changes were followed over a 1 hr post-task
      period. The results indicate significant physiological arousal and subjective
      distress as well as increases in NK cell cytotoxicity, numbers of circulating CD8
      suppressor/cytotoxic T cells and NK lymphocytes following mental arithmetic but
      not the control task. Immune measures generally returned to baseline by 1 hr
      after the stress. Naloxone did not block the increase in NK cell activity or cell
      numbers following the stressor and had no effect on the other physiological or
      subjective measures. Thus, the results do not support endogenous opioids as a
      primary mechanism for immune changes to this type of acute stress. Naloxone did,
      however, increase NK cell cytotoxicity during the video task without effecting NK
      cell numbers, suggesting naloxone itself can increase per-cell NK cytotoxicity.
      Affective ratings for the week preceding testing were inversely related to the
      increase in NK cell numbers during mental arithmetic. If the increase in NK cell
      numbers under brief stress is part of an adaptive response to potential injury,
      then our data suggest that increases in general distress may impede normal immune
      system adaptation. Acute stress paradigms may be used as potential probes for
      investigations of individual differences in immune system responsivity.

PMID- 7636779
TI  - Cardiovascular recovery from laboratory stress: biopsychosocial concomitants in
      older adults.
AB  - Although cardiovascular recovery may be important to long term cardiovascular
      health, its biopsychosocial correlates have received much less attention than the
      correlates of cardiovascular reactivity. Of the few studies that have examined
      recovery, fewer still have examined men and women over 60 yr of age. This study
      examined relationships of psychosocial factors (e.g. state anxiety, anger,
      avoidance coping, Type A behavior, etc.) with recovery in 186 older married men
      (n = 63) and women (n = 123) (mean age = 69.7 +/- 6.1 yr). Regressions were
      performed to explain recovery variability in systolic blood pressure (SBP),
      diastolic blood pressure (DBP), and heart rate (HR) in response to emotional and
      cognitive tasks. In each analysis, we controlled for the effects of gender, type
      of task, reactivity to the task, and other important covariates. Individuals with
      slower recovery had higher scores on anxiety (for SBP, p < 0.03 and DBP, p <
      0.01), higher scores on avoidance coping (for DBP and HR, p < 0.01), and lower
      scores on anger held in (for DBP, p < 0.01). Psychosocial factors may be
      important in explaining recovery in older adults.

PMID- 7636780
TI  - Viruses, neurosis and fatigue.

PMID- 7636781
TI  - Exploring widows' experiences after the suicide of their spouse.
AB  - 1. The widow of a spouse who committed suicide must cope with issues related to
      depression, anger, blame, guilt, and the stigma associated with suicide that
      makes recovery from this type of loss different for the survivors. 2. The
      predominant need of widows and widowers of suicide victims was to talk in an
      environment of acceptance and understanding, which could only be provided by
      other people who have had the same kind of experience. 3. There is no precise
      formula that exists to guide caregivers when assisting survivors of suicide
      victims, however suggestions include communicating with compassion; demonstrating
      care and concern; accepting the individual's grief; and offering and providing
      information.

PMID- 7636782
TI  - Psychiatric stress debriefing. Alleviating the impact of patient suicide and
      assault.
AB  - Psychiatrists and psychologists have developed the psychological autopsy into a
      debriefing tool, as well as a learning tool. Use of the CISD has been an
      effective protocol to help police, fire, ambulance, emergency room, and ICU
      personnel cope with the effects of violence and trauma. Psychiatric nurses and
      ancillary personnel also face frequent exposure to violence and trauma. The
      psychiatric debriefing protocol offers a practical intervention.

PMID- 7636783
TI  - Consistency of behavior: expect the unexpected.
AB  - Clinicians and lay people mistakenly expect behavior to be consistent across time
      and situations. However, the presence of a psychological disorder can cause large
      and seemingly inexplicable fluctuations in patient behavior. These fluctuations
      intrinsically are aversive, and increase the burden on family members. This
      article outlines the clinical implications of inconsistency in patient behavior.
      A practical set of guidelines for the mental health worked is issued.

PMID- 7636784
TI  - The vision of a nurse-coroner. A "protector of the living through the
      investigation of death".
AB  - 1. The coroner must possess medical knowledge to make judgments based on
      symptomatology, history, post-mortem appearance, toxicology, and other diagnostic
      studies combined with evidence revealed by other aspects of the investigation. 2.
      One role of the nurse-coroner is providing the families of the deceased what they
      need to survive the death in terms of factual information, accuracy in the
      determination of cause and manner of death, and psychological and, sometimes,
      physical support. 3. Nurse-coroners are the facilitators of information that is
      learned from the dead, so that living members of society will have healthier,
      happier, longer lives.

PMID- 7636785
TI  - Further research needed.

PMID- 7636786
TI  - Listening for a diagnosis.

PMID- 7636787
TI  - Nursing home residents' perceptions of the quality of their care.
AB  - This pilot study employed qualitative interviews to assess nursing home
      residents' perceptions of their "best" and "worst" experiences in the nursing
      home. Findings suggest residents are least satisfied with the care provided by
      nurse aides, and most satisfied with that provided by professional staff members.
      The quality of interpersonal relationships with staff was the basis for the
      majority of both residents' best and worst experiences. Qualitative analyses
      identified specific "adaptive responses" that were associated with how residents
      interpreted and responded to negative experiences with care.

PMID- 7636789
TI  - Will welfare reform help clients?

PMID- 7636790
TI  - Progesterone inhibition of the development of the luteolytic signal in cows.
AB  - Mated cows that subsequently undergo luteolysis have significantly lower plasma
      concentrations of progesterone than do cows in which pregnancy is maintained. Two
      groups of ovariectomized cows were treated with progesterone and oestradiol to
      recreate luteal phases exhibiting the extremes of plasma concentrations of
      progesterone (6.0 +/- 0.4 and 12.4 +/- 0.8 ng ml-1) normally seen in intact cows.
      The effect of this difference in progesterone on the development of the
      luteolytic signal was determined by monitoring the basal and oxytocin-stimulated
      plasma concentrations of the principal metabolite of prostaglandin F2 alpha' PGFM
      on days 12-16 of the simulated luteal phases. Basal PGFM concentrations were
      similar in the low and high progesterone groups on all days. The mean plasma
      concentration of PGFM showed a larger increase following oxytocin in the low
      progesterone group on days 13 and 14 (P < 0.05) and on days 15 and 16 (P < 0.1).
      These results demonstrate that a low plasma concentration of progesterone results
      in the development of a stronger luteolytic signal, and provide an explanation
      for the fact that cows with lower plasma concentrations of progesterone are more
      prone to embryo loss.

PMID- 7636788
TI  - New treatment for porphyria to be studied.

PMID- 7636792
TI  - Gene expression and protein distribution of collagen, fibronectin and laminin in
      bovine follicles and corpora lutea.
AB  - The aim of this study was to locate sites of expression and deposition of
      collagen, fibronectin and laminin in the bovine ovary. RNA from the granulosa and
      basement membrane/theca fractions of maturing follicles and from corpora lutea of
      the early, middle and late luteal phase was probed with cDNAs for collagen types
      I and IV, fibronectin and laminin. Antisera against collagens I and IV were used
      in western analysis of protein from follicular fluid, granulosa, basement
      membrane/theca and corpus luteum. Collagen subunits alpha 1(I) and alpha 2(I)
      were expressed in the basement membrane/theca but not in the granulosa of the
      follicle. They were also expressed in all luteal extracts, especially those from
      the early phase. Collagen alpha 2(IV) was highly expressed in the basement
      membrane/theca and to a lesser extent in corpora lutea. Collagen alpha 3(IV) was
      expressed in the granulosa, basement membrane/theca and early corpus luteum.
      Fibronectin 1 and laminin B2 were expressed in all tissues. Laminin B1 was
      expressed in all tissues except the granulosa. Collagen IV was immunodetected in
      all follicle extracts, with the strongest signal in the basement membrane/theca.
      Collagen I occurred in all luteal extracts and in the basement membrane/theca but
      not in follicular fluid or the granulosa. These results demonstrate tissue
      specific expression of ovarian structural proteins and suggest that changes occur
      during the progression from follicle to corpus luteum. The production of collagen
      IV in the follicle wall and of collagen I in the corpus luteum is consistent with
      previous biochemical studies. Evidence for collagen IV in the follicular antrum
      suggests that the follicle wall originates from granulosa as well as theca
      cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7636791
TI  - Isolation and partial characterization of rat sperm tail fibrous sheath proteins
      and comparison with rabbit and human spermatozoa using a polyclonal antiserum.
AB  - Rat sperm tail fibrous sheath was isolated using mechanical and chemical
      dissection methods from spermatozoa collected from the cauda epididymis. The
      procedures used to isolate the fibrous sheath were monitored by phase-contrast
      microscopy and purity was verified by electron microscopy. SDS-PAGE of isolated
      total fibrous sheath revealed at least 17 bands when stained with Coomassie
      brilliant blue and 20 bands with silver stain. The most intensely staining
      proteins, using both staining methods, were a double band at 80-87 kDa, and a
      band at 28.5 kDa, whereas with silver staining, bands at 66.2 kDa and kDa were
      also intensely stained. Electroelution following SDS-PAGE was used to isolate 11
      of these proteins (116.4, 87.5, 80.9, 66.2, 57.2, 49.7, 46.8, 37.3, 32.7, 28.5
      and 15.5 kDa). Amino acid analysis revealed that these proteins were abundant in
      aspartic and glutamic acid, glycine, serine and leucine, while histidine and
      phenylalanine were of low abundance. The content of cystine varied widely from
      9.4% to 1.4%. The amino termini of the 80.9 kDa, 32.7 kDa, 28.5 kDa and 15.5 kDa
      proteins were blocked. Immunofluorescence microscopy demonstrated that a
      polyclonal antiserum to isolated rat fibrous sheath was localized to the
      principal piece of the rat, rabbit and human spermatozoa, but in the rabbit it
      also labelled the equatorial region of the head. Western blotting detected all
      protein bands in isolated fibrous sheath and a similar range of proteins in the
      spermatozoa of rat and rabbit.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7636793
TI  - Glucose utilization by components of the mouse conceptus during early
      embryogenesis.
AB  - Mouse conceptuses were collected from female mice between day 6.5 and day 9.5 of
      pregnancy, dissected into their component parts and incubated for 2.5 h at 37
      degrees C in droplets of Hepes-buffered medium containing 1 or 5 mmol glucose l-1
      supplemented with 0.33 mmol pyruvate l-1 plus either 1 or 5 mmol (DL) lactate l-1
      under oil. Glucose disappearance and lactate appearance were measured
      enzymatically at the end of incubation. High glucose concentration doubled
      utilization of this substrate per microgram of embryonic protein, but the change
      in lactate concentration had no effect on glucose turnover. Over the whole period
      of development studied, tissue from the ectoplacental cone exhibited the lowest
      rate of glucose turnover of all tissues isolated. At day 8.5, there was little
      difference between yolk sac and embryonic tissues, but by day 9.5, the yolk sac
      had a higher rate of utilization of glucose than did embryonic tissues. By this
      time, the embryonic tissues had started to show some metabolic differentiation,
      with head and visceral tissue exhibiting 20% higher turnover of glucose than that
      of body tissue. Overall, the rate of glucose utilization fell as development
      progressed and the estimate of the relative rate of glucose utilization on day
      9.5 was half the value on day 6.5.

PMID- 7636794
TI  - Expression of two transgenes in in vitro matured and fertilized bovine zygotes
      after DNA microinjection.
AB  - Bovine zygotes produced by in vitro maturation-in vitro fertilization (IVM-IVF)
      were examined for their potential to serve as recipients of transgenes.
      Pronuclei, which were maximally visible at about 22 h after IVF, were injected
      with a SV40-LacZ construct (pSVON). Injected zygotes had lower cleavage rates
      (49.1%, n = 1162, P < 0.01) than did either noninjected controls (87.4%, n =
      1420) or noninjected zygotes in which pronuclei were not visible (67.6%, n =
      803). Zygotes that were injected into their pronuclei cleaved as well as zygotes
      injected cytoplasmically. At 48 h after injection, when most embryos had reached
      the four- and eight-cell stages, more zygotes in the pronuclear group (22.7%, n =
      125) stained positively for LacZ than did zygotes in the cytoplasmic group (8.0%,
      n = 125). A group of zygotes injected into the pronucleus with pSVON was cultured
      for 9 days. More morulae (10.8%, n = 134) than blastocysts (3.2%, n = 31)
      expressed the LacZ gene, indicating that silencing of expression occurred as
      development progressed. Another group of zygotes was injected with a beta-actin
      LacZ gene construct (pbActinLacZ) and, of the embryos assayed at 48 h, 10.6% (n =
      255) stained positively. At 9 days, 36.3% of morulae (n = 91) and 21% of
      blastocysts (n = 33) expressed the transgene. Almost all putative transgenic
      embryos injected with either construct showed a mosaic pattern of LacZ
      expression, with an average of only 2-3 cells staining at the eight-cell stage
      and the majority of cells in positive blastocysts showing no evidence of
      expression.

PMID- 7636795
TI  - Regulatory mechanisms of fowl sperm motility: possible role of endogenous myosin
      light chain kinase-like protein.
AB  - The motility of both intact and demembranated fowl spermatozoa was vigorous at 30
      degrees C, but decreased markedly following the addition of 1-(5
      chloronaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine hydrochloride (ML-9), a
      specific inhibitor of myosin light chain kinase (MLCK). Furthermore, the presence
      of a MLCK substrate peptide also inhibited the motility of demembranated
      spermatozoa at 30 degrees C. In contrast, the addition of N-[2
      (methylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride (H-8) or N-(2
      guanidinoethyl)-5-isoquinolinesulfonamide dihydrochloride (HA1004), specific
      inhibitors of cAMP-dependent protein kinase, did not appreciably affect the
      motility of either intact or demembranated spermatozoa. Cyclic AMP-dependent
      protein kinase substrate peptides were also ineffective for the inhibition of
      motility of demembranated spermatozoa at 30 degrees C. Immunoblotting of sperm
      extract, using an antibody to MLCK, revealed two major crossreacting proteins of
      130 kDa and 61-64 kDa, which corresponded to the molecular mass of MLCK. In
      addition, immunogold particles, which reacted with the anti-MLCK antibody, were
      observed around or on the axoneme at the ultrastructural level. These results
      suggest that the phosphorylation of axonemal protein(s) by MLCK, or a MLCK-like
      protein, rather than by cAMP-dependent protein kinase, may be involved in the
      maintenance of fowl sperm motility at 30 degrees C.

PMID- 7636796
TI  - Effect of follicular components on meiotic arrest and resumption in horse
      oocytes.
AB  - Two experiments were conducted to evaluate the effect of follicular components on
      the maintenance of meiotic arrest in horse oocytes. In Expt 1, oocytes were
      incubated for 24 h with follicular fluid, or with granulosa cells suspended
      either in medium or in follicular fluid at 25 x 10(6) cells ml-1. None of the
      treatments resulted in significant maintenance of the germinal vesicle stage over
      that of non-suppressive control. Culture with follicular fluid plus granulosa
      cells resulted in a significantly higher proportion of oocytes at metaphase I
      compared with controls. In Expt 2, oocytes were divided into those originally
      having compact or expanded cumuli. Oocytes were cultured with sheets of mural
      granulosa or sections of follicle wall, or after injection into intact dissected
      follicles. After incubation, half of the oocytes from each suppressive treatment
      were matured for 24 h. All three suppressive treatments were effective in
      maintaining oocytes at the germinal vesicle stage (no significant difference from
      control oocytes fixed directly after removal from the follicle). However, no
      treatment maintained normal viability of oocytes, as significantly fewer oocytes
      were at metaphase II after all the suppression-maturation treatments compared
      with the maturation control. The highest rate of post-suppression maturation was
      found in the mural granulosa treatment. Within this treatment, the proportion of
      oocytes in metaphase II was significantly higher for oocytes with expanded than
      for oocytes with compact cumuli (31% versus 11%, respectively; P < 0.05).
      Suppression by injection into an intact follicle was associated with a lack of
      progression to metaphase II during subsequent maturation.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7636797
TI  - Interactions between oestradiol and epidermal growth factor in endometrial
      stromal proliferation and differentiation.
AB  - The relationship between oestradiol and epidermal growth factor (EGF) in the
      control of endometrial proliferation and differentiation in cultures of human
      endometrial stromal cells was investigated. Oestradiol at a concentration of 10
      nmol l-1 increased the incorporation of both [3H]thymidine and [3H]leucine but
      the differences were significantly different from control only for [3H]leucine
      incorporation. Concentrations of 0.16, 1.6 and 16 nmol EGF l-1 significantly
      increased both [3H]thymidine (P < 0.01) and [3H]leucine incorporation (P < 0.01).
      The pure steroidal antioestrogen, ICI 182,780, inhibited any increase in
      [3H]thymidine and [3H]leucine incorporation stimulated by oestradiol in
      endometrial stroma. The monoclonal antibody, ICR 16, directed against the EGF
      receptor did not inhibit the oestradiol action in stromal cells, indicating that,
      in this model system, oestradiol does not act by inducing synthesis or release of
      EGF. However, ICI 182,780 potently inhibited the incorporation of [3H]thymidine
      stimulated by EGF in endometrial stromal cells, suggesting interdependence
      between oestradiol and EGF in the control of endometrial stromal proliferation.
      Oestrogen-free conditioned medium from endometrial stromal cultures did not
      stimulate either [3H]thymidine or [3H]leucine incorporation, suggesting that
      oestradiol did not stimulate the secretion of a trophic factor from endometrial
      stromal cells.

PMID- 7636798
TI  - Increased number of cells and metabolic activity in male human preimplantation
      embryos following in vitro fertilization.
AB  - The number of cells and metabolic activity of male and female human
      preimplantation embryos were examined to determine whether male embryos are more
      advanced than female embryos following in vitro fertilization (IVF). The
      metabolic activity of embryos fertilized normally was assessed daily by non
      invasive measurement of pyruvate and glucose uptake and lactate production
      between days 2 and 6 after insemination. On day 6, the numbers of nuclei from the
      trophectoderm and inner cell mass of blastocysts were counted by differential
      labelling and fluorescence microscopy. Nuclei were then recovered and the sex of
      the embryos identified using nested primers to amplify the amelogenin gene and
      pseudogene sequences on the X and Y chromosomes, respectively. Development of
      male and female embryos were then compared retrospectively. From 69 of 178 (39%)
      embryos that developed to the blastocyst stage, the sex of 57 was determined; 21
      (37%) were male and 36 (63%) female. The number of cells in male embryos was
      significantly greater on day 2 (P < 0.005), and this difference was maintained up
      to the blastocyst stage (in both the trophectoderm and the inner cell mass),
      although differences were not always significant. Pyruvate uptake was
      significantly higher by male embryos between days 2 and 5 (P < 0.05). Glucose
      uptake and lactate production were significantly higher in male embryos on days 4
      5 (P < 0.05); this difference was not significant on days 5-6. Extrapolation from
      differences in the number of cells indicates that female embryos are
      approximately 4.5 h delayed in their development from day 2 onwards compared with
      male embryos.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7636799
TI  - Effect of active immunization against testosterone on plasma gonadotrophin
      concentrations, spermatogenic function, testicular blood flow, epididymis mass
      and mating behaviour in adult rams.
AB  - The long-term effects of active immunization against testosterone were studied in
      rams, with particular reference to blood concentrations of gonadotrophin and
      testosterone, spermatogenesis, testis blood flow and mating behaviour. Ten 18
      month-old Merino rams, kept on pasture, were studied for 1 year. Every 2 months,
      five rams received injections of BSA in Freund's adjuvant and five other rams
      were treated with testosterone-3(o-carboxymethyl)oxime-BSA as immunogen. Anti
      testosterone antibodies (mean titre: 1:4484 +/- 582, after boosters) were
      maintained in the circulation, with the help of regular booster injections. In
      time, immunization reduced live mass in testosterone-immunized rams; however,
      there was no effect on testicular volume throughout the whole study. In
      testosterone-immunized rams, significantly higher concentrations of
      gonadotrophins were found in jugular venous plasma, as well as increased
      concentrations of total plasma testosterone. LH pulse frequency, amplitude and
      nadir were increased significantly in testosterone-immunized rams. After 12
      months of immunization, no differences were found in the number of spermatozoa
      per ejaculate, in daily sperm production or in testis mass between the two groups
      of rams; however, testicular blood flow (per testis) and epididymis mass were
      significantly reduced in testosterone-immunized rams. Testosterone immuno
      neutralization also resulted in a significant reduction in the number of mounts
      culminating in ejaculation performed during a 10 min trial carried out on a
      number of occasions during the experiment. Additional information on these rams
      was collected 3 months after castration. However, there were no significant
      differences in mean plasma LH and FSH concentrations, either before, or after, a
      single GnRH injection between the two groups of rams at this time.

PMID- 7636800
TI  - Influence of postpartum energy restriction on energy status, plasma LH and
      oestradiol secretion and follicular development in suckled beef cows.
AB  - Effects of postpartum energy restriction, parity and time after parturition on
      energy status (measured by glucose, insulin, non-esterified fatty acids (NEFAs)
      and beta-hydroxybutyrate), LH secretion and follicular growth were investigated
      in ten primiparous and nine multiparous suckled cows. Females were allocated by
      parity, body mass and body condition score at calving to diets supplying either
      100% (CE, n = 10) or 70% (LE, n = 9) of energy requirements until day 70
      postpartum. Metabolic parameters were measured every week from calving to day 70
      postpartum. Blood samples were collected at intervals of 15 min for 10 h on day
      30 and day 50 after parturition for LH measurement. Ovaries were examined between
      days 20 and 30 and days 40 and 50 postpartum by ultrasonography. Energy supply
      affected mean plasma concentrations of glucose (CE: 0.64 +/- 0.01 g l-1 versus
      LE: 0.61 +/- 0.01 g l-1; P < 0.05) and NEFA (CE: 168 +/- 17 mu eq l-1 versus LE:
      309 +/- 18 mu eq l-1; P < 0.01) but by day 70 postpartum, glucose and NEFA
      concentrations were not significantly different between the two groups. LH pulse
      amplitude and frequency were not affected by energy supply (P > 0.10). However,
      at day 30 postpartum, LH pulse frequency was negatively correlated with plasma
      concentration of NEFA (r = -0.61; P < 0.01). Cows fed diets supplying 100% of
      energy requirements had more large follicles than did cows fed low energy diets
      (CE: 0.82 +/- 0.05 versus LE: 0.31 +/- 0.05; P < 0.05). The size of the largest
      follicle was greater in CE cows than in LE cows (CE: 10.2 +/- 0.1 mm versus LE:
      8.7 +/- 0.2 mm; P < 0.05). Between 40 and 50 days postpartum, the size of the
      largest follicle was negatively correlated with NEFA concentration (r = -0.5; P <
      0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7636801
TI  - Effects of ovariectomy and FecBB genotype on the median charge and circulating
      half-life of pituitary FSH isoforms of ewes.
AB  - This study investigated the effects of short-term (20 days) ovariectomy, the
      effects of FSH assay (radioimmunoassay, receptor assay or in vitro bioassay) and
      of FecBB genotype on the characteristics of pituitary FSH from Booroola ewes.
      Pituitary extracts were obtained from ovariectomized homozygous carriers (BB) and
      non-carriers (++, n = 8 per genotype) and ovary-intact controls (n = 4 per
      genotype). The extracts (n = 4 per genotype per treatment) were subjected to
      agarose suspension electrophoresis and the eluates were assayed by the three FSH
      methods. There were significant effects of ovariectomy (P < 0.01) and assay
      system (P < 0.05) but not of genotype on the median charge of FSH isoforms. The
      mean +/- SEM migration rates for FSH in intact and ovariectomized ewes were 0.469
      +/- 0.006 and 0.439 +/- 0.006 albumin mobility units, respectively (P < 0.01),
      indicating a shift to more basic isoforms after short-term ovariectomy. When the
      pituitary extracts were subjected to anion-exchange HPLC, there was a significant
      (P < 0.01) shift to more basic isoforms in the ovariectomized ewes as shown using
      agarose electrophoresis, and no gene effects were noted. When the pituitary
      extracts (n = 4-8 per group) were injected into mature female mice, there were no
      significant effects of ovariectomy or genotype on the circulating half-lives of
      the pituitary FSH isoforms. These results indicate that after short-term
      ovariectomy, the increase in plasma FSH concentrations is accompanied by a shift
      in the median charge of pituitary FSH isoforms without any observable change in
      their metabolic clearance rates.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7636803
TI  - Sequential changes in ovarian follicular dynamics in Bos indicus heifers before
      and after nutritional anoestrus.
AB  - This study examined the effects of live mass on ovarian follicular dynamics in
      heifers before and after the onset of nutritional anoestrus. The effects of
      decreased live mass on secretion of progesterone, LH and FSH were also
      investigated. Ovarian characteristics were monitored in 16 postpubertal Brahman
      heifers using daily transrectal ultrasonography. After two normal oestrous
      cycles, 11 heifers (treatment group) were allocated to a restricted diet, until
      the cessation of their oestrous cycles, that resulted in a decrease in live mass
      of 0.8 kg day-1. Heifers were then fed an ad libitum diet, resulting in
      increasing live mass until resumption of oestrous cycles. Five heifers (control
      group) were fed an unrestricted diet throughout the experimental period. The
      concentrations of progesterone in plasma were monitored twice a week and the
      concentrations of LH and FSH were determined on day 6 after ovulation, before
      initiation of dietary restriction, after a 17% decrease in live mass and after
      the onset of anoestrus in the treatment group. Onset of anoestrus was preceded by
      linear decreases in the size of ovarian follicles and corpora lutea, and in the
      persistence of the first dominant follicles of oestrous cycles. These changes
      were proportional to the decrease in live mass (P < 0.001). The frequency of
      pulses of LH or mean concentration of FSH on day 6 of the oestrous cycle were not
      changed after a 17% decrease in live mass, and did not increase following the
      onset of anoestrus, although concentrations of progesterone were < 0.2 ng ml-1,
      suggesting that release of LH was suppressed at this time.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7636802
TI  - Hormone concentrations in the caudal vena cava during the first ovarian
      follicular wave of the oestrous cycle in heifers.
AB  - Changes in pulsatile secretion of LH, FSH, oestradiol and progesterone were
      related to the growth phase, early plateau phase and regression phase of the
      first ovarian dominant follicle of the oestrous cycle in Bos indicus heifers.
      Relationships between these hormones during the three phases were also
      investigated. Accurate measurements of episodic ovarian steroid secretion were
      obtained by catheterizing the caudal vena cava via the lateral saphenous vein;
      the tip of the catheter was positioned just cranial to the ovarian vein using
      transrectal ultrasonography. Pulsatile secretion of oestradiol was increased only
      during the growth phase of the dominant follicle and was associated with high
      frequency release of LH pulses. However, mean concentrations of oestradiol were
      reduced when the dominant follicle attained its maximum diameter. Between the
      growth and plateau phases, as the amount of progesterone released increased and
      oestradiol released decreased, LH pulse frequency and mean concentration of LH
      decreased. Pulses of LH released were followed within 15 min by increases in mean
      concentrations of oestradiol (P < 0.001); however, there was no apparent
      relationship between LH and progesterone release (P = 0.19). Although there was
      little evidence of pulsatile release of FSH, mean concentrations of FSH were
      increased by 0.2 ng ml-1 (P = 0.04) during the plateau phase, which was on
      average 2.1 days before the day of emergence of the second dominant follicle of
      the oestrous cycle. This increase in FSH, in conjunction with the decrease in
      secretion of oestradiol, may be an indication of the loss of functional dominance
      by the first dominant follicle of the oestrous cycle.

PMID- 7636804
TI  - Responses of prepubertal and mature rams to thyroidectomy.
AB  - Thyroidectomy of seasonally breeding birds and mammals prevents the return to a
      state of sexual quiescence at the end of the breeding season. In starlings,
      thyroidectomy also causes premature sexual maturity. In this study, the effect of
      thyroidectomy upon the time of sexual maturity of prepubertal (8 week-old) ram
      lambs was examined. Thyroidectomy of four prepubertal and six mature rams was
      performed early in the spring. These and sham-operated controls were maintained
      in ambient photoperiods (south-west England). Scrotal circumference and serum LH,
      FSH, prolactin and thyroxine were measured every 2 weeks. In both the prepubertal
      lambs and the mature rams, scrotal circumference increased significantly within 5
      weeks of thyroidectomy. FSH concentrations increased significantly in the mature
      rams after thyroidectomy. The relatively high FSH concentrations of
      thyroidectomized animals at the start of the experiment were maintained, but the
      FSH concentrations of intact lambs decreased during the late spring. These
      results provide the first indication that the timing of puberty in seasonally
      breeding mammals is a thyroid-dependent phenomenon.

PMID- 7636805
TI  - Regulation by epidermal growth factor of prostaglandin production and
      cyclooxygenase activity in sensitized rat endometrial stromal cells in vitro.
AB  - The effect of epidermal growth factor on prostaglandin production and
      cyclooxygenase activity in endometrial stromal cells isolated from the uteri of
      ovariectomized rats sensitized for the decidual cell reaction was examined.
      Treatment with epidermal growth factor (40 ng ml-1) for 24 h caused approximately
      6.9., 3.4-, and 4.1-fold increases in prostaglandin E2, prostaglandin F2 alpha
      and 13,14-dihydro-15-keto- prostaglandin F2 alpha accumulation in the media of
      cultured cells. The increase in prostaglandin E2 accumulation induced by
      epidermal growth factor was inhibited by alpha-amanitin (2 micrograms ml-1),
      cycloheximide (0.5 micrograms ml-1) and dexamethasone (5 mumol l-1). Epidermal
      growth factor increased cyclooxygenase activity in the stromal cells in a time
      dependent fashion and this increase in activity was also inhibited by alpha
      amanitin, cycloheximide and dexamethasone. These results provide evidence that
      epidermal growth factor stimulates prostaglandin production in rat endometrial
      stromal cells from uteri sensitized for the decidual cell reaction through a
      mechanism that involves an increase in cyclooxygenase activity.

PMID- 7636806
TI  - In vitro fertilization and embryo development of Japanese field voles (Microtus
      montebelli).
AB  - Optimal conditions for in vitro fertilization of Japanese field voles (Microtus
      montebelli) were analysed. The medium used was a modified Krebs-Ringer
      bicarbonate devised for in vitro fertilization in rats. Ovulated eggs and
      epididymal spermatozoa were co-incubated in vitro at 37 degrees C under 5% CO2 in
      air for 6 h, and the eggs were fixed with 2.5% (w/v) glutaraldehyde, stained with
      0.25% (v/v) acetolacmoid and examined for evidence of fertilization at the
      pronuclear stage. Although the fertilization rate with spermatozoa preincubated
      at 1-2 x 10(8) cells ml-1 for 2 h was very low (1-13%), it was significantly
      increased (43-51%, P < 0.05) when spermatozoa were preincubated at a lower
      concentration (1-2 x 10(7) cells ml-1). Furthermore, the fertilization rate was
      significantly higher with 1 mmol hypotaurine l-1 (74.0%) than without hypotaurine
      (44.4%, P < 0.05). Fertilization rates of spermatozoa preincubated at 1-2 x 10(7)
      cells ml-1 for 0.5 or 2 h were similar (69.0% and 73.6%), but a longer
      preincubation (10 h) resulted in a significantly lower fertilization rate (56.8%,
      P < 0.01). Vole spermatozoa preincubated for 2 h penetrated the zona pellucida 2
      h after insemination, and the sperm heads became decondensed 3 h after
      insemination. At 6 h after insemination, male and female pronuclei were found in
      most penetrated eggs. When the eggs were left in the fertilization medium without
      washing and cultured for 96 h after insemination, they developed to two-cell
      (82.6%), four-cell (60.9%), eight-cell (23.2%) and morula/blastocyst (8.7%)
      stages in modified Krebs-Ringer bicarbonate supplemented with 1 mmol hypotaurine
      l-1.

PMID- 7636807
TI  - Nonmitochondrial oxygen utilization by rabbit blastocysts and surface production
      of superoxide radicals.
AB  - A minimum value for nonmitochondrial oxygen utilization in rabbit blastocysts at
      day 6 post coitum was determined by measuring oxygen consumption in the presence
      of cyanide. A microcathode oxygen electrode was used to monitor oxygen
      concentration continuously during blastocyst incubation in a newly devised
      culture medium, and the uninhibited blastocyst was found to consume 2.79 +/- 0.09
      microliters O2 h-1 cm-2. This rate was reduced by 51% in the presence of 1 mmol
      KCN l-1. The addition of nitroblue tetrazolium to the cyanide-containing medium
      reduced net oxygen consumption by an additional 23% as the nitroblue tetrazolium
      was reduced to formazan. The ability of rabbit blastocysts to reduce nitroblue
      tetrazolium in the presence of cyanide was investigated using a
      spectrophotometric assay. Fractionation of blastocyst cells revealed that the
      enzymatic activity chiefly responsible for formazan production partitioned with
      the membrane/particulate fraction and could be solubilized by the detergent NP40.
      The enzyme was NAD(P)H-dependent, did not require divalent cations for activity,
      and appeared to contain no haeme moiety. The rate of formazan production in the
      spectrophotometric assay was markedly reduced by the presence of superoxide
      dismutase. The oxygen electrode and spectrophotometer data indicate that there is
      a superoxide-generating NAD(P)H oxidase on the blastocyst surface. Calculations
      based on the average surface area of rabbit blastocysts at day 6 show that these
      embryos can produce at least 8 nmoles of superoxide per embryo h-1. Potential
      deciduogenic effects of blastocyst-derived superoxide and its dismutated product,
      hydrogen peroxide, are discussed.

PMID- 7636808
TI  - Effect of active immunization against oestradiol in developing ram lambs on
      plasma gonadotrophin and testosterone concentrations, time of onset of puberty
      and testicular blood flow.
AB  - Merino ram lambs were actively immunized against oestradiol-6 (o-carboxy methyl)
      oxime-BSA conjugate at 14 weeks of age and received a booster injection 4 weeks
      later. This treatment led to an increase in plasma concentrations of
      gonadotrophin and tended to enhance the increase in testicular volume until 26
      weeks of age; however, testis size and mass at time of castration (30 weeks of
      age) were similar to values in BSA-immunized lambs. Detrimental effects were
      observed in some oestradiol-immunized ram lambs, for example a steep decline in
      testicular volume towards the end of the experiment, the presence of large
      vacuoles within the seminiferous epithelium and, in one lamb, few germ cell at 30
      weeks of age. Testicular blood plasma flow was significantly reduced in
      oestradiol-immunized lambs (P < 0.01). The steroidogenic function of the testis
      was markedly enhanced in oestradiol-immunized lambs as reflected by high plasma
      concentrations of testosterone measured at 22, 26 and 30 weeks of age and by high
      testosterone production calculated from blood flow and venous-arterial
      differences at 30 weeks of age. Nevertheless, total live mass gain over the 16
      week study was not increased in oestradiol-immunized lambs. Testicular biopsies
      were taken at 22 and 26 weeks of age in half of the lambs in each treatment
      group. Testicular volume measured at castration was decreased in control lambs in
      which biopsies were taken (P < 0.05), and plasma concentrations of testosterone
      measured at 30 weeks of age were significantly lower in oestradiol-immunized
      lambs in which biopsies were taken (P < 0.02) compared with lambs in which no
      biopsy had been taken. It is concluded that active immunization against
      oestradiol in ram lambs does not advance the time of onset of puberty and does
      not confer any reproductive or maturational advantages.

PMID- 7636809
TI  - G protein expression and second messenger formation in human granulosa cells.
AB  - The expression of heterotrimeric (alpha beta gamma subunits) GTP-binding
      regulatory proteins (G proteins) and the activation of G protein-linked receptors
      in human granulosa cells were investigated. The cells were obtained from
      stimulated follicles in women undergoing in vitro fertilization and were cultured
      in serum-supplemented medium. Immunoblotting with specific antibodies showed that
      granulosa cell membranes express alpha s, alpha i3 alpha i1,2, alpha q,11 and
      beta subunits. Three antibodies against alpha o failed to detect this protein.
      The cells responded to hCG and to prostaglandin E2 with a dose-dependent increase
      in cAMP formation, confirming the functional activation of G alpha s. The alpha 2
      adrenoceptor agonist, clonidine, inhibited hCG-stimulated cAMP formation and this
      effect was blocked with pertussis toxin, thus involving a Gi-type protein, most
      likely G alpha i2. Oxytocin provoked an increase in formation of inositol
      phosphates and intracellular calcium concentration, which was partly pertussis
      toxin resistant, providing evidence of G alpha q,11 activation. However, a
      significant component of the response to oxytocin could be blocked by pertussis
      toxin, indicating Gi-mediated phospholipase C activation (by either alpha i or
      beta gamma subunits). These data demonstrate the presence of G proteins in
      granulosa cells and suggest a complex regulation of hormonal signalling. The
      concentration of cAMP in these cells depended on the balance of G alpha s:G alpha
      i activation, whereas activation of the inositol phospholipid pathway and rises
      in intracellular calcium involved both Gq,11 and Gi pathways.

PMID- 7636810
TI  - Cervical opening in relation to progesterone and oestradiol during heat in beagle
      bitches.
AB  - The relationship between hormonal profile and cervical opening and closure was
      analysed during heat in seven bitches. The bitches were studied each day from the
      beginning of pro-oestrus until 5 days after cytological metoestrus. Vaginography
      was performed using a radiopaque contrast dye injected through an insemination
      probe and blood samples were collected daily. The opening of the cervix was
      observed, in pro-oestrus, 2.6 +/- 2.8 days before the LH peak. The progesterone
      and oestradiol values at that time were 2.0 +/- 2.4 nmol l-1 and 171.1 +/- 133.1
      pmol l-1, respectively. The opening of the cervix was observed concurrent with
      the day of the maximal value of the oestradiol:progesterone ratio, just before
      the decline of oestrogen preceding the LH peak. Differences between the
      oestradiol:progesterone ratio the day before, the day of and the day after
      opening were significant. The closure of the cervix occurred 6.7 +/- 1.4 days
      after the LH peak and 2.6 +/- 1 days before the first sign of cytological
      metoestrus. The progesterone and oestradiol concentrations at that time were 68.9
      +/- 15.4 nmol l-1 and 16 +/- 10.3 pmol l-1, respectively. All bitches were in
      cytological oestrus when the cervix closed. These data indicate that there is a
      relationship between hormonal profile and cervical opening and that breeding
      success may also be temporarily limited, not only by oestrous behaviour, but also
      by cervical closure. In the beagle colony studied, a blood concentration of 60
      nmol progesterone l-1 would give a good indication that no success will follow
      artificial vaginal insemination or natural mating.

PMID- 7636811
TI  - Glutamine transport by mouse inner cell masses.
AB  - Mouse blastocysts take up glutamine by specific transport systems. Glutamine is
      an important precursor for macromolecular synthesis and a potential alternative
      fuel to glucose. This study compared glutamine uptake in blastocysts and isolated
      inner cell masses and characterized the major participating systems in the
      latter. Inner cell masses take up glutamine by facilitated transport systems. The
      identity of these was investigated using substrate competition and kinetic
      studies. Na(+)-dependent uptake of 13 mumol glutamine l-1 was inhibited by 60% by
      1 mmol tryptophan l-1, 25% by 1 mmol 2-amino-2-norbornanecarboxylic acid l-1 and
      50% by 1 mmol lysine l-1. Furthermore, 1 mmol 2-methyl(amino)isobutyric acid
      (MeAIB) l-1 inhibited uptake by 29%. Kinetic analysis of MeAIB-resistant uptake
      revealed a predominant Na(+)-dependent facilitated uptake system with Km and Vmax
      values of 434 +/- 72 mumol l-1 and 237 +/- 38 fmol per inner cell mass per 10
      min, respectively. The inhibition of Na(+)-dependent uptake by tryptophan, lysine
      and the analogue 2-amino-2-norbornanecarboxylic acid suggests that most uptake of
      glutamine by inner cell masses occurs via the same system that predominates in
      whole blastocysts, Bo,+. The period of assay was so brief that significant
      participation of the inner cell mass in whole blastocyst uptake was precluded
      showing that system Bo,+ is expressed by both the trophectoderm and inner cell
      mass components of the blastocyst. However, MeAIB inhibited uptake by inner cell
      masses but not by blastocysts. This MeAIB-sensitive uptake had a Km value of 4.3
      +/- 1.7 mmol l-1 and a Vmax value of 451 +/- 119 fmol per inner cell mass per 10
      min. These characteristics suggest the first embryonic appearance of system A,
      which is a common Na(+)-dependent transporter in many somatic cells.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7636812
TI  - Effects of time of insemination relative to ovulation, as determined by
      ultrasonography, on fertilization rate and accessory sperm count in sows.
AB  - The effects of the timing of insemination relative to ovulation on fertilization
      rate, accessory sperm count and early embryo development were studied in sows.
      Oestrus detection was performed at intervals of 8 h. Sows were artificially
      inseminated once with 3 x 10(9) spermatozoa. Transrectal ultrasonography was
      performed at intervals of 4 h to determine when ovulation occurred and sows were
      killed at 120 +/- 6 h after ovulation. For each insemination-ovulation interval
      of 8 h, fertilization rates were as follows: > 48 h, 35% (n = 1); 48-40 h, 51 +/-
      36% (n = 6); 40-32 h, 54 +/- 36% (n = 14); 32-24 h, 79 +/- 32% (n = 19); 24-16 h,
      94 +/- 11% (n = 24); 16-8 h, 92 +/- 21% (n = 24); 8-0 h, 95 +/- 22% (n = 21) and
      for the sows that were inseminated after ovulation: 0 to -8 h, 75 +/- 38% (n =
      26); -8 to -16 h, 74 +/- 43% (n = 15) and < -16 h, 0% (n = 1). The median
      accessory sperm count differed among the groups from 1 (insemination 40-48 h
      before ovulation) to 126 (insemination 0-8 h after ovulation) (P = 0.0001).
      Within each 8 h time interval, the normal embryos from sows with less than 90%
      normal embryos were less developed and had a lower sperm count than did the
      normal embryos from sows with more than 90% normal embryos (P < 0.05).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7636813
TI  - Pitfalls in the interpretation of studies: III.

PMID- 7636814
TI  - Complementary medicine: common misconceptions.
AB  - Complementary medicine (CM), defined as health care which lies for the most part
      outside the mainstream of conventional medicine, is gaining popularity in Britain
      and elsewhere. In the UK the most prevalent therapies are manipulation (used by
      36% of the population), herbalism (24%) homoeopathy (16%) and acupuncture (16%).
      Due to the heterogeneity of CM, it is often problematic to generalize. The debate
      about the usefulness of CM is often regrettably emotional, and thus unproductive.
      In the pursuit of a more fruitful way ahead, the following highlights some of the
      main arguments from both 'sides' and tries to disguise them as misconceptions.

PMID- 7636815
TI  - The diagnosis of Lyme disease.

PMID- 7636816
TI  - Sir Richard Francis Burton: explorer, anthropologist, irregular physician.
AB  - Travellers to remote areas seem to have a magical aura. Indigenous folk often
      seek them out asking for medical treatment. It does not matter whether or not the
      traveller is in fact a doctor. Non-medical travellers have rendered good care,
      and by so doing ensured the success of their expedition. Nevertheless, there are
      reservations about 'playing doctor' and many travellers shun the role. Others,
      however, have purposefully impersonated doctors and capitalized on their medical
      fraud.

PMID- 7636817
TI  - Why did Moses stammer? and, was Moses left-handed?
AB  - Moses, the great lawgiver, '... the chief of the prophets' according to
      Maimonides, probably had a speech defect. 'I am not a man of words ... for I am
      of slow speech, and of a slow tongue', Moses states, and later he pleads '... I
      am of uncircumsized lips, and how shall Pharaoh hearken unto me'. Most
      authorities consider these quotations to mean that he stammered.

PMID- 7636818
TI  - Fungal feeding-line infections: beware the eyes and teeth.
AB  - Twenty-four fungal feeding-line infections occurred in 17 patients during 1984
      1992. Thirteen were receiving long-term home parenteral feeding and, in them, the
      first infection occurred after a median of 30 months (range 1-120) continuous
      feeding with a line that had been in situ for a median of 20 months (range 1-37).
      Four were receiving short-term feeding through a line that had been inserted 1-2
      months previously. At the time of the first infection all patients were febrile
      and most were anaemic (15/16), however a leucocytosis was rare (three of 16). The
      fungi isolated were Candida albicans(6), Candida parapsilosis(5), Candida
      glabrata(2), Candida guillermondii(2) and other species (2). In 16 patients, the
      feeding-line was removed at the time of the first infection and no other
      treatment was given, and no other complications occurred in eight (50%) of these.
      In 11, the line was reinserted a median of 7 days after removal (range 1-11).
      Four patients (24%) developed a Candida infection of the eye 1-8 weeks after the
      diagnosis, uveitis (2) and endophthalmitis (2) which, in one patient, led to
      complete blindness in one eye. Two patients had recurrent infections which began
      within a month of dental therapy. In one, the infections stopped after dental
      extractions and, in the other, after a dental clearance. An ophthalmoscopic
      examination should be performed in all patients with a fungal feeding-line
      infection. Recurrent candidal infections may have a dental origin.

PMID- 7636820
TI  - Improving the quality of cancer registration data.
AB  - Cancer registration is an essential element of any cancer control strategy. Data
      quality is, however, of paramount importance. This paper sets out some of the
      ways in which the quality of cancer registration data might be improved. In
      particular, the potential contribution of clinicians and pathologists is
      highlighted.

PMID- 7636819
TI  - Analgesia for venous cannulation: a comparison of EMLA (5 minutes application),
      lignocaine, ethyl chloride, and nothing.
AB  - Three commonly available local anaesthetics were compared, in a controlled trial,
      for use before venous cannulation. The pain of application of the local
      anaesthetic, the pain of cannulation, and the rate of successful cannulations
      were compared. The value of EMLA cream applied for 5 min was questioned. Venous
      cannulation with a 20G venflon was found to be significantly more painful than
      the application of any of the local anaesthetics (P < 0.01). Lignocaine 1%,
      injected subcutaneously, and ethyl chloride spray significantly reduced the pain
      of venous cannulation (P < 0.01). The use of lignocaine did not result in
      significantly more failed cannulations than the control group. It was concluded
      that local anaesthesia should be used before venous cannulation, even for 20G
      cannulae.

PMID- 7636821
TI  - Neurological presentations of hypothyroidism: the importance of slow relaxing
      reflexes.
AB  - Neurological sequelae of hypothyroidism are well recognized and relatively
      common. Neurological symptoms occurring as a presenting feature of this illness
      are, however, uncommon. Here we report three patients who presented in such a way
      and in whom the diagnosis was only suspected because of slow relaxing reflexes.

PMID- 7636822
TI  - Case reports: a sections' view.

PMID- 7636823
TI  - What is the place of the clinical case report in medical publishing?

PMID- 7636824
TI  - The TAO of medical history: or, why do it?

PMID- 7636825
TI  - Cyclosporin-responsive hidradenitis suppurativa.
AB  - Hidradenitis suppurativa, a chronic inflammatory condition of the apocrine gland
      follicles, may rarely be complicated by pyoderma gangrenosum (PG). We report such
      a case, in which the immunosuppressant cyclosporin A (CyA) was given to treat PG
      and a dramatic improvement occurred in the patient's intractable perineal HS.

PMID- 7636826
TI  - Primary systemic amyloid with nail dystrophy.
AB  - We report a patient with the classical cutaneous findings of primary systemic
      amyloidosis, due to myeloma. He had developed a nail dystrophy, which is a
      recognized, but rare, feature in systemic amyloid.

PMID- 7636827
TI  - Follicular atrophoderma in association with congenital pseudarthrosis of the
      tibia.
AB  - Follicular atrophoderma has always been associated with other congenital
      malformations including, Conradi-Hunermann syndrome, Bazex's syndrome and
      keratosis palmaris et plantaris dissipata. Congenital pseudarthrosis of the tibia
      has usually been associated with neurofibromatosis. We report a case of
      follicular atrophoderma in association with congenital pseudarthrosis of the
      tibia: a previously unreported association with, in our case, a good outcome for
      the pseudarthrosis.

PMID- 7636828
TI  - Oculocutaneous albinism and bruising in two sisters--probable Hermansky-Pudlak
      syndrome.
AB  - Cases of Hermansky-Pudlak syndrome may present to the dermatologist,
      ophthalmologist or haematologist. Classically the diagnosis rests on the triad of
      oculocutaneous albinism, a bruising tendency and the presence of characteristic
      pigmented-containing cells in the bone marrow. Specific tests of platelet
      function can, however, suggest the diagnosis without recourse to invasive
      techniques. We describe the disease in two young sisters.

PMID- 7636829
TI  - Cold urticaria, raised IgE and HIV infection.
AB  - We present a patient with cold urticaria as an unusual and late cutaneous
      manifestation of acquired immunodeficiency syndrome. The severe CD4 cell
      depletion and markedly elevated serum IgE levels in our patient provide some
      insights into certain aspects of immune regulatory mechanisms.

PMID- 7636830
TI  - Chronic bullous dermatosis of childhood: relapse after puberty.
AB  - Chronic bullous dermatosis of childhood (CBDC) is a distinctive subepidermal
      blistering disorder that characteristically involves the perioral area, lower
      trunk, inner thighs and genitalia. Direct immunofluorescence shows a linear band
      of IgA at the dermoepidermal junction (DEJ). The eruption usually begins before
      the age of 6 years and is typically described as self-limiting, clearing with a
      few months or years. Chronic bullous dermatosis of childhood has many clinical
      and immunopathological similarities with adult linear IgA disease (LAD) and it
      has been suggested that they represent different manifestations of the same
      disease. We report a case of CBDC which started at 2 years of age and which has
      relapsed twice, first at age 6 years and then again, after puberty, at age 17
      years.

PMID- 7636831
TI  - Music and melancholia.

PMID- 7636832
TI  - Neurogenic pain.

PMID- 7636833
TI  - Musculoskeletal pain.

PMID- 7636834
TI  - Gastric lymphoma, carcinoma and Helicobacter pylori.

PMID- 7636835
TI  - Beethoven's nephropathy and death.

PMID- 7636836
TI  - The cost effectiveness of combined rapid tests (Multistix) in screening for
      urinary tract infections.

PMID- 7636837
TI  - Earliest documented applications of X-rays.

PMID- 7636838
TI  - Cognitive arousal induced by alcohol withdrawal.

PMID- 7636839
TI  - Ginseng--a root just like a carrot?

PMID- 7636840
TI  - Technetium-99m-labeled HOE 140: a potential bradykinin B2 receptor imaging agent.

PMID- 7636841
TI  - 5,7-dihydro-3-[2-[1-(phenylmethyl)-4-piperidinyl]ethyl]-6H- pyrrolo[3,2-f]-1,2
      benzisoxazol-6-one: a potent and centrally-selective inhibitor of
      acetylcholinesterase with an improved margin of safety.
AB  - A series of N-benzylpiperidines (2a-d, 10) with novel isoxazole-containing
      tricycles has been prepared. This series has shown potent in vitro inhibition of
      the enzyme acetylcholinesterase (AChE), with IC50S = 0.33 - 3.6 nM. Compound 2a
      was the most potent inhibitor with an IC50 = 0.33 +/- 0.09 nM. Derivatives 2a-d
      and 10 displayed weak in vitro inhibition of butyrylcholinesterase (BuChE) with
      IC50S = 600 - 23,000 nM. The most selective compound was 2a with a BuChE/AChE
      ratio in excess of 4 orders of magnitude (> 10,000). Pyrrolobenzisoxazole 2a also
      displayed a favorable profile in vivo. In microdialysis experiments, 2a produced
      a 200% increase in extracellular levels of acetylcholine (ACh) at a dose of 0.4
      mg/kg in freely moving, conscious rats. Peripheral side effects (salivation ED50
      = 26 +/- 1.5 mg/kg) and acute lethality (LD50[1 h] = 42 mg/kg) were observed at >
      60-fold higher doses. These data indicate that 2a is an AChE inhibitor with good
      central selectivity and a favorable margin of safety. Compound 2a, designated as
      CP-118,954, is currently in clinical development for the treatment of cognitive
      disorders.

PMID- 7636842
TI  - Structure-activity relationships of the potent combined endothelin-A/endothelin-B
      receptor antagonist Ac-DDip16-Leu-Asp-Ile-Ile-Trp21: development of endothelin-B
      receptor selective antagonists.
AB  - The endothelins (ETs) are a family of bicyclic 21-amino acid-containing peptides
      that are highly potent and prolonged vasoconstrictors. The discovery of potent ET
      antagonists will facilitate the understanding of the physiological and/or
      pathophysiological role of ET. Structure-activity studies have revealed the
      importance of the C-terminal hexapeptide (residues 16-21) of ET (His16-Leu17
      Asp18-Ile19-Ile20-Trp21) to the development of potent antagonists at both
      receptor subtypes (ETA and ETB). In particular, it has been shown that Ac-DDip16
      Leu-Asp-Ile-Ile-Trp21 (Dip = 3,3-diphenylalanine) has low nanomolar affinity for
      the two endothelin receptor subtypes and is a functional antagonist of ET
      activity, both in vitro and in vivo at both receptors. Herein, we will describe
      the structure-activity relationships of Ac-DDip16-Leu-Asp-Ile-Ile-Trp21 (PD
      142893) with a particular emphasis on modifications that lead to enhanced
      receptor affinity and/or individual receptor subtype selectivity. In particular,
      we will demonstrate how we utilized PD 142893 to develop ETB receptor selective
      ligands and the pharmacological differences that exist between species ETB
      receptors with respect to their affinity for C-terminal hexapeptide antagonists.

PMID- 7636843
TI  - Synthesis and structure-activity relationships of stilbene retinoid analogs
      substituted with heteroaromatic carboxylic acids.
AB  - Retinoids elicit biological responses by activating a series of nuclear
      receptors. Six retinoid receptors belonging to two families are currently known:
      retinoic acid receptors (RAR alpha,beta,and gamma) and retinoid X receptors (RXR
      alpha,beta,and gamma). Stilbene retinoid analogs of retinoic acid (RA), such as
      (E)-4-[2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)prope n-1-
      yl]benzoic acid (TTNPB, 1) and (E)-4-[2-(5,6,7,8-tetrahydro-3,5,5,8,8-pentamethyl
      2-naphthalenyl)pro pen-1- yl]benzoic acid (3-methyl-TTNPB, 2), display
      differential RAR and RXR activities, depending on the substituent at C3 of the
      naphthalene ring. We report here structural modifications of the benzoate moiety
      of 2 that result in analogs with greater RXR selectivity as well as those with
      pan-agonist (activate both RAR and RXR receptors) activities, analyze the
      structural features that impart receptor selectivity, and describe a
      stereoselective method for the synthesis of these analogs. The biological
      activities associated with the RAR and RXR receptors were examined by testing
      representative examples with different receptor activation profiles for their
      ability to induce tissue transglutaminase (Tgase) activity in a human
      promyelocytic leukemia cell line (HL-60 cdm-1) and to inhibit tumor-promoter
      induced ornithine decarboxylase (ODC) activity in hairless mouse skin. These
      results suggest that RAR agonists and RXR agonists may have different therapeutic
      applications. Finally, we show that RXR agonists are significantly reduced in
      teratogenic potency relative to RAR agonists and may therefore have significant
      advantages in clinical practice.

PMID- 7636844
TI  - Synthesis, structure, and pharmacological evaluation of the stereoisomers of
      furnidipine.
AB  - The synthesis and pharmacological activities of the four stereoisomers of methyl
      tetrahydrofuran-2-ylmethyl 2,6-dimethyl-4-(2'-nitrophenyl)-1,4-dihydropyridine
      3,5- dicarboxylate(furnidipine) are reported. The four isomers were synthesized
      by a modified Hantzsch synthesis by reaction of (-)- or (+)-tetrahydrofuran-2
      ylmethyl 3-aminocrotonate and methyl 2-[(2'-nitrophenyl)methylene]acetoacetate
      or, alternatively, by reaction of (-)- or (+)-tetrahydrofuran-2-ylmethyl 2-[(2'
      nitrophenyl)methylene]acetoacetate and methyl 3-aminocrotonate. The 1:1
      diastereomeric mixtures thus obtained were separated by chromatography, using
      poly(D-phenylglycine) as the chiral stationary phase. The enantiomeric purity of
      the stereoisomers was determined by a high-performance liquid chromatography
      chiral stationary phase technique (HPLC-CSP). Attempts to obtain crystals of a
      single stereoisomer failed in different solvents, while methanol crystallization
      of the product obtained from (+/-)-tetrahydrofuran-2-ylmethyl 2-[(2'
      nitrophenyl)methylene]acetoacetate and methyl 3-aminocrotonate yielded good
      quality crystals of the most insoluble racemate which proved to be a mixture of
      the (SS)/(RR) enantiomers by X-ray crystallography. Conformational analysis of
      the stereoisomers, assuming rotation of the aryl substituent and ester groups,
      shows small energy differences (about 4 kcal.mol-1) between the most and the
      least favorable conformations. Binding studies were performed using
      [3H]isradipine as a reference ligand. The results showed stereospecificity of the
      furnidipine isomers in brain, ileum, and cardiac tissues, the (SS)- and (SR)
      isomers clearly being more potent than their (RR)- and (RS)-enantiomers. The (SS)
      and (SR)-isomers were also more selective on cerebral tissue when compared with
      ileal and cardiac preparations.

PMID- 7636845
TI  - Synthesis, structure elucidation, and biochemical evaluation of 7 alpha- and 7
      beta-arylaliphatic-substituted androst-4-ene-3,17-diones as inhibitors of
      aromatase.
AB  - The inhibition of aromatase, the cytochrome P450 enzyme complex responsible for
      the conversion of androgens to estrogens, may be useful for the endocrine
      treatment of breast cancer. Previously, several 7 alpha-thio-substituted
      androstenediones have been shown to be potent inhibitors of aromatase. Recent
      research has focused on producing a more metabolically stable aromatase inhibitor
      by replacing the carbon-sulfur bond at the 7 alpha-position with a carbon-carbon
      bond. The new inhibitors, 7 alpha-arylaliphatic-substituted androst-4-ene-3,17
      diones (2-4), have alkyl chains of varying length between the steroid and the
      aryl ring at the 7 alpha-position. The desired targets were synthesized via a 1,6
      conjugate addition of the appropriate cuprate to 17 beta-(tert
      butyldimethylsiloxy)androsta-4,6-dien-3-one (7). The synthesis also resulted in
      the formation of the 7 beta-substituted diastereomers (10-11 and 13) as minor
      products. Initial assignments of the 7 alpha-phenethyl and 7 beta-phenethyl
      diastereomers were made using highfield 1-D and 2-D NMR studies. The assignment
      of the diastereomers was confirmed using X-ray crystallography. These compounds
      were all good inhibitors of aromatase in vitro when assayed using microsomes
      isolated from human placenta. The 7 alpha-substituted androst-4-ene-3,17-diones
      (2-4) were effective inhibitors with apparent Kis of 13-19 nM. The corresponding
      17 beta-hydroxy analogs (8 and 14) and the 7 beta-substituted androstenediones
      (13 and 16) were less effective inhibitors with apparent Kis of 36-44 nM. Thus, a
      new series of 7 alpha-arylaliphatic-substituted androst-4-ene-3,17-diones has
      been synthesized, and the compounds are potent competitive inhibitors of
      aromatase.

PMID- 7636847
TI  - Peptide mimetics of thyrotropin-releasing hormone based on a cyclohexane
      framework: design, synthesis, and cognition-enhancing properties.
AB  - The design and synthesis of peptide mimetics of thyrotropin-releasing hormone
      (TRH) in which the peptide backbone is entirely replaced by a cyclohexane
      framework are described. The cis-1,3,5-trisubstituted ring was expected to permit
      key pharmacophoric groups to adopt conformations consistent with proposed
      bioactive conformations of the peptide. Compounds were synthesized by a
      stereoselective synthesis starting from L-glutamic acid. In a behavioral model of
      cognition in which TRH is active, the mimetics are potent, active compounds,
      exhibiting oral activity. One analog (26, (1S,3R,5(2S),5S)-5-[[5-oxo-1
      (phenylmethyl)-2-pyrrolidinyl]-methyl]-5- [(1H-imidazol-5
      yl)methyl]cyclohexaneacetamide) was radiolabeled for binding studies and
      evaluated in other binding assays and pharmacological tests. Competition binding
      of 26 vs [3H]MeTRH to rat brain slices suggests a two-site model for ligand
      binding with IC50's of 1 microM and 3 mM. Direct binding of [3H]-26 shows a
      biphasic curve with IC50's of 80 and 49 microM, respectively. Further studies
      would be needed to establish a link between the novel binding site(s) and the
      behavioral activity of 26 and TRH analogs.

PMID- 7636846
TI  - Synthesis and antiviral activity of 6-benzyl analogs of 1-[(2
      hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) as potent and selective anti
      HIV-1 agents.
AB  - Several 6-benzyl analogs of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (1;
      HEPT) were synthesized and evaluated for their anti-HIV-1 activity. LDA (lithium
      diisopropylamide) lithiation of 5-ethyluracil derivatives 7 and 8 and subsequent
      reaction with an aryl aldehyde gave 6-(arylhydroxymethyl)-5-ethyluracil
      derivatives 9-12. 6-(Arylhydroxymethyl)-5-isopropyluracil derivatives 15-18 were
      prepared from the 5-isopropyl-2-thiouracil derivatives 13 and 14 by the above
      procedure following oxidative hydrolysis of the thione. Preparation of the target
      5-alkyl-1-(alkoxymethyl)-6-benzyluracil derivatives 27-34 was carried out by
      acetylation of 9-14 followed by Pd-catalyzed hydrogenolysis. The 1-butyl- (37 and
      39) and 1-(2-methoxyl)- (38 and 40) 5-alkyl-6-benzyluracils were synthesized by 1
      alkylation of the 3-phenacyl derivatives 35 and 36 with alkyl halides followed by
      deprotection of the 3-phenacyl group. Compounds synthesized in this study
      inhibited HIV-1 replication in MT-4 cells in the submicromolar to namomolar
      concentration range. From this series of compounds, 6-benzyl-1-(ethoxymethyl)-5
      isopropyluracil (33) was selected for clinical evaluation.

PMID- 7636848
TI  - Cardioselective ammonium, phosphonium, and sulfonium analogues of alpha
      tocopherol and ascorbic acid that inhibit in vitro and ex vivo lipid peroxidation
      and scavenge superoxide radicals.
AB  - Analogues of alpha-tocopherol and ascorbic acid with permanently cationic
      substituents, i.e., phosphonium (8, 9), sulfonium (11), acylhydrazinium (13, 14),
      and ammonium (1, 16, 21), were synthesized, and the 2R and 2S enantiomers of the
      alpha-tocopherol analogues 1, 8, 11, and 13 were separated. The compounds were
      found to scavenge lipoperoxyl and superoxide radicals in vitro and accumulate in
      heart tissue (cardioselectivity) as demonstrated by measurement of ex vivo
      inhibition of lipid peroxidation in mouse heart homogenates and confirmed by HPLC
      determination of drug concentrations for 1 and 11. The 2R and 2S enantiomers of 1
      inhibited ex vivo lipid peroxidation to an equal extent. Thus the in vivo uptake
      into myocytes (cardioselectivity) is independent of the geometry at the chiral
      center and common to permanently cationic compounds.

PMID- 7636849
TI  - (E)-4-(2-[[3-(indol-5-yl)-1-oxo-2-butenyl]amino]phenoxy)butyric acid derivatives:
      a new class of steroid 5 alpha-reductase inhibitors in the rat prostate. 1.
AB  - A series of (E)-4-(2-[[3-(indol-5-yl)-1-oxo-2-butenyl]amino]phenoxy)butyric acid
      derivatives was prepared, and the derivatives were demonstrated to be potent
      inhibitors of steroid 5 alpha-reductase in the rat prostate. The structure
      activity relationships were as follows. An alpha-branched alkyl or benzyl
      substituent of proper size at position 1 of the indole is crucial for optimal
      enzyme inhibitory activity. N-Methylation of the amide NH resulted in complete
      loss of activity. Thus, coplanarity of the benzene ring and amide moiety is
      essential for such activity. Among the compounds prepared, (E)-4-(2-[[3-[1-[bis(4
      fluorophenyl)methyl]indol-5-yl]-1-oxo-2- butenyl]-amino]phenoxy)butyric acid (57,
      KF18678) was one of the most potent compounds (rat prostate 5 alpha-reductase
      IC50 = 3.3 nM).

PMID- 7636850
TI  - Design and synthesis of renin inhibitors: incorporation of transition-state
      isostere side chains that span from the S1 to the S3 binding pockets and
      examination of P3-modified renin inhibitors.
AB  - A series of renin inhibitors were designed to examine the topography of the
      contiguous binding pocket of renin that is normally occupied by the P1 and P3
      side chains. Molecular modeling suggested that extending the P1 hydrophobic side
      chain into the adjacent hydrophobic S3 enzyme pocket was feasible. Novel
      transition state isosteres with modified P1-->P3 side chains were synthesized and
      provided enhanced binding affinity when incorporated into renin inhibitors in
      which the P3 Phe was substituted by Gly. In a complementary approach, the binding
      affinities of a variety of P3-P4-modified peptidomimetic renin inhibitors that
      lacked substantial hydrophobic side chains at these sites were measured.

PMID- 7636851
TI  - Farnesyl diphosphate-based inhibitors of Ras farnesyl protein transferase.
AB  - The rational design, synthesis, and biological activity of farnesyl diphosphate
      (FPP)-based inhibitors of the enzyme Ras farnesyl protein transferase (FPT) is
      described. Compound 3, wherein a beta-carboxylic phosphonic acid type
      pyrophosphate (PP) surrogate is connected to the hydrophobic farnesyl group by an
      amide linker, was found to be a potent (I50(FPT) = 75 nM) and selective inhibitor
      of FPT, as evidenced by its inferior activity against squalene synthetase
      (I50(SS) = 516 microM) and mevalonate kinase (I50(MK) = > 200 microM). A
      systematic structure-activity relationship study involving modifications of the
      farnesyl group, the amide linker, and the PP surrogate of 3 was undertaken. Both
      the carboxylic and phosphonic acid groups of the beta-carboxylic phosphonic acid
      PP surrogate are essential for activity, since deletion of either group results
      in 50-2600-fold loss in activity (6-9, I50 = 4.6-220 microM). The farnesyl group
      also displays very stringent requirements and does not tolerate one carbon
      homologation (12, I50 = 17.7 microM), substitution by a dodecyl fragment (14, I50
      = 9 microM), or introduction of an extra methyl group at the allylic position
      (18, I50 = 55 microM). Modifications around the amide linker group of 3 were more
      forgiving, as evidenced by the activity of N-methyl analog (21, I50 = 0.53
      microM), the one carbon atom shorter farnesoic acid-derived retroamide analog
      (32, I50 = 250 nM), and the exact retroamide analog (49, I50 = 50 nM). FPP
      analogs such as 3, 32, and 49 are novel, potent, selective, small-sized,
      nonpeptidic inhibitors of FPT that may find utility as antitumor agents.

PMID- 7636852
TI  - Reduced-size antagonists of luteinizing hormone-releasing hormone active in
      vitro.
AB  - A series of reduced-size analogs of LHRH was designed with the length varying
      from nine to two amino acids. These compounds were tested in vitro for the LH
      suppression in cultured rat pituitary cells treated with 1 ng of LHRH. The best
      analogs were also tested in vivo for their antiovulatory activity in rats. It
      appeared that terminal amino acids as well as the presence of Arg or ILys in the
      sequence are both crucial for the antagonism. The most potent antagonist in this
      series was a heptapeptide, AcDNal-Ser-Tyr-DNal-Leu-Arg-ProNHEt, which completely
      inhibited LH release at the dose 0.1 microgram and inhibited ovulation at 1000
      micrograms/rat. For fragments shorter than heptapeptide the inhibition of LH
      release was observed at the dose 100 micrograms of the analog.

PMID- 7636853
TI  - 4-Diazinyl- and 4-pyridinylimidazoles: potent angiotensin II antagonists. A study
      of their activity and computational characterization.
AB  - A series of N-[biphenylyl(tetrazolyl)methyl]-2-butylimidazoles containing
      variously substituted diazine or pyridine moieties either as their free bases or
      N-oxide derivatives attached to the 4-position of the imidazole ring was
      synthesized and tested for interaction with the AT1 receptors of rat adrenal
      cortex membranes (receptor binding assay). Some compounds were then chosen for
      further evaluation in vivo in the A II-induced pressor response in conscious
      normotensive rats. The most potent in the AT1 binding assay were found to be
      compounds in which the diazine or pyridine ring nitrogen is adjacent to the point
      of attachment between the two heteroaromatic rings such as 2-butyl-4-(3,6
      dimethylpyrazin-2-yl)-1-[[2'-(1H-tetrazol-5-y l)-biphenyl-4- yl]methyl]-1H
      imidazole (3b) or 2-butyl-4-[5-(methoxycarbonyl)pyrid-2-yl]-1-[[2'-(1H-tetrazol++
      +-5- yl)biphenyl-4-yl]methyl]-1H-imidazole (6c). The binding affinities and oral
      activities of the pyridine N-oxide imidazoles in which a stabilizing group ortho
      to the pyridine ring nitrogen is present were markedly improved as in 2-butyl-4
      [(3-methoxycarbonyl)-6-methyl-N-oxopyridin-2-yl]-1-[[2'- (1H- tetrazol-5
      yl)biphenyl-4-yl]methyl]-1H-imidazole 31b. Molecular modeling studies were
      carried out to determine the molecular electrostatic potential values of related
      model systems and to correlate their receptor interaction energies with the
      observed activities of our compounds.

PMID- 7636854
TI  - Balanced AT1/AT2 receptor antagonists. 4. XR510 and related 5-(3
      amidopropanoyl)imidazoles possessing equal affinity for the AT1 and AT2
      receptors.
AB  - The identification of the AT1 and AT2 receptor subtypes has stimulated interest
      in developing balanced angiotensin II receptor antagonists. A series of 5-(3
      amidopropanoyl)imidazoles has been prepared which possess balanced affinity for
      the AT1 and AT2 receptors. XR510 (1), 1-[[2'
      [[(isopentoxycarbonyl)amino]sulfonyl]-3- fluoro(1,1'-biphenyl)-4-yl]methyl]-5-[3
      (N-pyridin-3- ylbutanamido)propanoyl]-4-ethyl-2-propyl-1H-imidazole, potassium
      salt, exhibits subnanomolar affinity for both receptor sites. XR510 is very
      active in lowering blood pressure in renal hypertensive rats and furosemide
      treated dogs following oral administration.

PMID- 7636855
TI  - 5-Methyl-6-phenyl-1,3,5,6-tetrahydro-3,6-methano-1,5-benzodiazocine-2,4-dione (BA
      41899): representative of a novel class of purely calcium-sensitizing agents.
AB  - BA 41899 (5-methyl-6-phenyl-1,3,5,6-tetrahydro-3,6-methano-1,5- benzodiazocine
      2,4-dione, 6) is a structurally novel 1,5-benzodiazocine derivative and
      represents the prototype of a hitherto unknown class of positive inotropic Ca(2+)
      sensitizing agents. It is completely devoid of phosphodiesterase (PDE) III
      inhibitory activity or any other known inotropic mechanism. BA 41899 (6) exhibits
      a pharmacological in vitro profile comprising Ca(2+)-sensitizing, positive
      inotropic, and negative chronotropic effects. CGP 48506 ((+)-6), the (+)
      enantiomer of BA 41899 (6), enantiospecifically carries Ca2+ sensitization by up
      to a full pCa unit and a corresponding positive inotropic effect. Conversely, the
      negative chronotropic action resides in the corresponding (-)-enantiomer, CGP
      48508 ((-)-6). All the effects are exerted in the low micromolar range. The
      positive inotropic action of CGP 48506 ((+)-6) is associated with a decelerating
      effect on contraction and, more prominently, relaxation dynamics in isolated
      guinea pig atria. In contrast to Ca(2+)-sensitizing PDE inhibitors, CGP 48506
      ((+)-6) does not increase maximum Ca(2+)-activated force in myocardial skinned
      fibers.

PMID- 7636856
TI  - Novel hexakis(areneisonitrile)technetium(I) complexes as radioligands targeted to
      the multidrug resistance P-glycoprotein.
AB  - Transport substrates and modulators of the human multidrug resistance (MDR1) P
      glycoprotein (Pgp) are generally lipophilic cationic compounds, many with
      substituted aryl moieties. We sought to synthesize aromatic technetium-isonitrile
      complexes to enable functional detection in vivo of Pgp expression in tissues. A
      series of substituted aromatic isonitrile analogs were synthesized from their
      corresponding amines by reaction with dichlorocarbene under phase transfer
      catalyzed conditions, and the non-carrier-added hexakis(areneisonitrile)Tc-99m(I)
      complexes were produced by reaction with pertechnetate in the presence of sodium
      dithionite. Cellular accumulation in vitro, whole body biodistribution, and the
      imaging properties of these lipophilic, monocationic organometallic complexes
      were determined in Chinese hamster lung fibroblasts expressing MDR Pgp, in normal
      rats, and in rabbits, respectively. For this initial series, verapamil (50
      microM), the classical Pgp modulator, significantly enhanced cellular
      accumulation or displaced binding of Tc complexes of 1b, 1d, 1h, 2a, 2d, 3a, and
      3b, indicative of targeted interactions with Pgp. Most complexes, despite their
      modestly high lipophilicity, were excluded by the blood/brain barrier, and
      several complexes displayed simultaneously high hepatobiliary and renal excretion
      in vivo, consistent with the physiological expression pattern of Pgp in these
      tissues. Selected Tc- and Re-areneisonitrile complexes of this class have
      potential applicability to the functional imaging and modulation, respectively,
      of MDR Pgp in human tissues.

PMID- 7636857
TI  - (+/-)-(Z)-2-(aminomethyl)-1-phenylcyclopropanecarboxamide derivatives as a new
      prototype of NMDA receptor antagonists.
AB  - (+/-)-(Z)-2-(Aminomethyl)-1-phenylcyclopropane-N,N-diethylcarbo xamide
      (milnacipran, 1), a clinically useful antidepressant, and its derivatives were
      prepared by an improved method and were evaluated as NMDA receptor antagonists.
      Of these, milnacipran (1), its N-methyl and N,N-dimethyl derivatives, 7 and 8,
      respectively, and its homologue 12 at the aminomethyl moiety had binding affinity
      for the receptor in vitro (IC50: 1, 6.3 +/- 0.3 microM; 7, 13 +/- 2.1 microM; 8,
      88 +/- 1.4 microM; 12, 10 +/- 1.2 microM). These also protected mice from NMDA
      induced lethality. These compounds would be important as anovel prototype for
      designing potent NMDA-receptor antagonists because of their characteristic
      structure, which clearly differentiated them from known competitive and
      noncompetitive antagonists to the receptor.

PMID- 7636858
TI  - Flexible 1-[(2-aminoethoxy)alkyl]-3-ar(o)yl(thio)ureas as novel
      acetylcholinesterase inhibitors. Synthesis and biochemical evaluation.
AB  - A series of flexible 1-(2-aminoethoxy)-3-ar(o)yl(thio)ureas was synthesized and
      assessed for antiacetylcholinesterase activity. This series was designed in order
      to optimize the spacer length linking the two pharmacophoric moieties, i.e., the
      basic nitrogen and the ar(o)yl(thio)-urea unit, and to test compounds with
      greater conformational flexibility. Thus, the replacement of the previously
      described spacer, 4-piperidinylethyl, by a linear ethoxyethyl chain gave
      compounds of slightly comparable potency, providing that they were correctly
      substituted. The results show that this new flexible spacer is compatible with
      high inhibitory activities. The optimal chain length corresponds to five
      methylene groups, allowing an efficient interaction between the two
      pharmacophoric units and the two reported hypothetical enzyme hydrophobic binding
      sites. Moreover, the initially optimized benzyl group, attached to the basic
      nitrogen, was found to be advantageously replaced by a cyclohexyl group, showing
      that an aromatic residue does not represent a prerequisite for activity.

PMID- 7636859
TI  - Effect of lipophilicity at N-1 on activity of fluoroquinolones against
      mycobacteria.
AB  - The dramatic increase in drug resistant Mycobacterium tuberculosis has caused a
      resurgence in research targeted toward these organisms. As part of a systematic
      study to optimize the quinolone antibacterials against mycobacteria, we have
      prepared a series of N-1-phenyl-substituted derivatives to explore the effect of
      increasing lipophilicity on potency at this position. The compounds, synthesized
      by the modification of a literature procedure, were evaluated for activity
      against Gram-negative and Gram-positive bacteria, Mycobacterium fortuitum and
      Mycobacterium smegmatis, and the results correlated with log P, pKa, and other
      attributes. The activity of the compounds against the rapidly growing, less
      hazardous organism M. fortuitum was used as a measure of M. tuberculosis
      activity. The results demonstrate that increasing lipophilic character by itself
      does not correlate with increased potency against mycobacteria. Rather, intrinsic
      activity against Gram-negative and/or Gram-positive bacteria is the governing
      factor for corresponding activity against mycobacteria.

PMID- 7636860
TI  - Synthesis and sigma binding properties of 2'-substituted 5,9 alpha-dimethyl-6,7
      benzomorphans.
AB  - The synthesis and sigma 1 and sigma 2 binding properties of several (+)- and (-)
      2-benzyl- and 2-dimethylallyl-2'-substituted-5,9 alpha-dimethyl-6,7-benzomorphans
      (3 and 4) are presented. In agreement with previously reported binding data for 2
      substituted 5,9 alpha-dimethyl-2'-hydroxy-6,7-benzomorphans (N-substituted-N
      normetazocine), all (1S,5S,9S)-(+)-isomers showed higher affinity for the sigma 1
      site than the corresponding (1R,5R,9R)-(-)-isomers. Replacement of the 2'-hydroxy
      group of (+)-2-benzyl-5,9 alpha-dimethyl-2'-hydroxy-6,7-benzomorphan [(+)-1f]
      with a 2'-NH2 and 2'-N(CH3)2 [(+)-3b and (+)-3c, respectively] had only a small
      effect on the sigma 1 Ki values. Changing the 2'-hydroxy group of (+)-1f to an H,
      F, Cl, Br, I, NHAc, or NHSO2CH3 resulted in a 5-fold or greater loss in potency.
      In contrast, replacement of the 2'-hydroxy group of (+)-2-(dimethylallyl)-5,9
      alpha-dimethyl-2'-hydroxy-6,7-benzomorphan [(+)-1b, (+)-pentazocine] with a 2'-H
      or 2'-F group resulted in a 2-fold increase in potency. Conversion of (+)-1f to
      its 2'-desoxy analogue (+)-2d resulted in a 27.5-fold loss in affinity. This
      suggests that (+)-1f and other N-substituted benzomorphan analogues may be
      binding to single sigma 1 receptors in a different way or to different sigma 1
      receptors. (-)-Pentazocine [(-)-1b] and its 2'-fluoro analogue, (-)-2
      (dimethylallyl)-5,9 alpha-dimethyl-2'-fluoro-6,7-benzomorphan [(-)-4a] showed the
      highest potency for the sigma 2 binding site.

PMID- 7636861
TI  - Synthesis and sigma binding properties of 1'- and 3'-halo- and 1',3'-dihalo-N
      normetazocine analogues.
AB  - The synthesis and sigma 1 and sigma 2 binding properties of several 1'- and 3'
      halo- and 1',3'-dihalo-substituted analogues of (+)-N-benzyl- and (+)- and (-)-N
      dimethylallyl-N-normetazocine are presented. Structure-activity relationship
      analyses of the binding data showed that halogen substitution at the 1'-position
      of these N-substituted N-normetazocine analogues had little effect on sigma 1
      binding affinity, whereas 3'-halo substitution as well as 1',3'-dihalo
      substitution resulted in a reduction of affinity. sigma 2 affinity was increased
      by the presence of a 3'-bromo substituent in this series of (+)-N-substituted N
      normetazocines.

PMID- 7636862
TI  - Synthetic chemical diversity: solid phase synthesis of libraries of C2 symmetric
      inhibitors of HIV protease containing diamino diol and diamino alcohol cores.
AB  - Solid phase synthesis of non-oligomeric organic compounds has been pursued for
      high-efficiency generation of large numbers of structurally diverse compounds for
      drug screening. Known as chemical diversity libraries or combinatorial libraries
      (when the synthesis is carried out in a combinatorial fashion), these compounds
      can be used for de novo discovery of drug leads or for expedient structure-
      activity relationship (SAR) studies. To expand the scope of solid phase synthesis
      beyond the capability of the traditional method of solid phase synthesis for
      peptides, a strategy was developed for bi-directional solid phase synthesis
      starting with diamino alcohol or diamino diol core structures. The strategy
      relies on using bifunctional linkers to modify the core structures,
      simultaneously protecting the hydroxyl group or the diol moiety of the core and
      providing a carboxyl group for attachment of the modified cores to a solid
      support. The two NH2 groups of the modified cores attached to the solid support
      were then deprotected and reacted with a wide variety of amine-reactive reagents
      (carboxylic acids, sulfonyl chlorides, isocyanates, chloroformates, etc.) to
      extend the molecule in both directions. This strategy was successfully applied to
      automated parallel synthesis of a library of C2 symmetric inhibitors of HIV
      protease containing the known symmetry-based diamino diol and diamino alcohol
      core structures, thus enabling expedient access of large numbers of analogs in
      this series. A library of over 300 discrete compounds was synthesized using this
      methodology in order to identify potent (IC50 < 100 nM) HIV protease inhibitors
      with reduced size. This paper describes the technical aspects of this technology.

PMID- 7636863
TI  - PLS analysis of distance matrices to detect nonlinear relationships between
      biological potency and molecular properties.
AB  - Although the statistical method of partial least squares (PLS) is widely used for
      the analysis of the relationship between molecular properties and biological
      potency, it is recognized that PLS detects only linear relationships. We tested
      two types of properties: simulated univariate data and electrostatic molecular
      field as a function of Hammett sigma constants. In both cases we compared
      relationships in which the function is linear, asymptotic, or rises to an optimum
      and then falls. We found that PLS analysis of the matrix of the distances between
      every pair of compounds detects all three types of relationships with the same
      quality of cross-validation. The successful application of the method requires
      that the distance matrices be constructed such that each contains only
      information about one property (for example, the electrostatic field around the
      functional group of interest). Carbo and Hodgkin similarities perform less well
      than distances.

PMID- 7636865
TI  - Synthesis and antitumor activity of various 6-demethylmitomycins and 6-demethyl-6
      halomitomycins.
AB  - A series of 6-demethylmitomycins and 6-demethyl-6-halomitomycins having various
      mitomycin skeletons were synthesized, taking into account the electronic effect
      toward the quinone moiety and the partition coefficients. Treatment of enones 15
      and 16 with selenenamide or N-halosuccinimide-Et2NH afforded the 6-demethyl
      intermediates 17, 18, and 21-24 via the tandem Michael addition/retro-Mannich
      reaction sequence. Subsequent conversions into the mitomycin skeletons resulted
      in the formation of the desired derivatives 7a-c, 8a-c, 11a-c, and 12a,b. These
      mitomycin derivatives including 3a-c and 4a-c were evaluated for their
      anticellular activity against HeLa S3 cells and antitumor activity against
      Sarcoma 180 in mice. The anticellular activity of 1 and 3a-c depends on the
      substituent at the C-6 position and the order of increasing activity is H < CH3 <
      Br < Cl. A similar tendency was observed in their antitumor potency (ED50). The
      activities of 9 and 11a-c also follow a pattern similar to that of 1 and 3a-c.
      Compounds 4b,c, 8b,c, and 12b having both a halogen at the C-6 position and a
      methoxy group at the C-7 position did not show the activities because of the
      instability of the compounds. Interestingly, a correlation between the
      anticellular activity (IC50) and the partition coefficients (log kappa')
      determined by HPLC was observed within the compounds studied except the unstable
      compounds, while their antitumor activity (ED50 or T/C) did not correlate with
      the quinone reduction potential (E1/2). These results would indicate the
      importance of the C-6 substituents and the mitomycin skeletons for exhibiting
      both anticellular and antitumor activities.

PMID- 7636864
TI  - Synthesis and in vitro and in vivo antitumor activity of a series of trans
      platinum antitumor complexes.
AB  - The synthesis of a series of platinum complexes of trans coordination geometry
      [centered around the general formula, trans
      ammine(amine)dichlorodihydroxoplatinum(IV) plus corresponding
      tetrachloroplatinum(IV) or Pt(II) counterparts] is described as part of a drug
      discovery program to identify more effective platinum-based anticancer drugs,
      particularly targeted toward the circumvention of resistance to cisplatin.
      Complexes have been evaluated for antitumor activity using in vitro and in vivo
      tumor models. In vitro against a panel of cisplatin-sensitive and -resistant
      human tumor cell lines (predominantly ovarian), many of the trans platinum
      complexes studied (e.g., 1, R = cyclohexyl) exhibited comparable potency to
      cisplatin and also overcame acquired cisplatin resistance, where resistance was
      due mainly to either reduced drug uptake or enhanced platinum-DNA adduct removal.
      Moreover, 14 trans complexes showed significant in vivo antitumor activity
      against the subcutaneous murine ADJ/PC6 plasmacytoma model; all were platinum(IV)
      complexes, 13/14 possessing axial hydroxo ligands the other possessing axial
      ethylcarbamato ligands. Where tested, all of their respective platinum(II) or
      tetrachloroplatinum(IV) counterparts were inactive. Notably, three
      dihydroxoPt(IV) complexes (18, 29, 34) (R = c-hexyl, c-heptyl, and 1-adamantyl)
      retained some efficacy against a cisplatin-resistant variant of the ADJ/PC6.
      Compounds 18 (trans-[PtCl2(OH)2NH3-(RNH2)]) R = c-C6H11, 22, R = Me3C, 27, R = n
      C6H13, 28, R = PhCH2, and 36 (trans-[PtBr2(OH)2NH3(c-C6H11NH2)]) also produced
      evidence of antitumor activity (> 5 days growth delay) against subcutaneously
      grown advanced stage human ovarian carcinoma xenografts. These data demonstrate
      that a series of trans-ammine(amine)dichlorodihydroxoplatinum(IV) complexes are
      active in vivo against both murine and human subcutaneous tumor models and
      represent potential leads to a new generation of platinum-based anticancer drug.

PMID- 7636866
TI  - Antihyperglycemic N-sulfonyl-1a,2,6,6a-tetrahydro-1H,4H- [1,3]dioxepino[5,6
      b]azirines: synthesis, X-ray structure analysis, conformational behavior,
      quantitative structure-property relationships, and quantitative structure
      activity relationships.
AB  - A series of 1-sulfonyl-1a,2,6,6a-tetrahydro-1H,4H- [1,3]dioxepino[5,6-b]azirines,
      4, has been synthesized and evaluated for its effects on blood glucose-decreasing
      activity. These derivatives were prepared from 4,7-dihydro-1,3-dioxepins 1 via
      vic(acylamino)halogenodioxepanes 2 and dioxepinoazirines 3. Quantitative
      structure--property relationship and quantitative structure--activity
      relationship models, based on X-ray and molecular mechanics analyses, to our
      knowledge the first in the field of antihyperglycemics, were developed. They
      allow the prediction of properties (RP-HPLC attention times) and activities
      (hypoglycemic activity ratio) by the Connolly's molecular surface areas. The lead
      compound in these models, sulfonyldioxepinoazirine 4i, expressed superior
      antihyperglycemic activity in comparison to metformin in alloxanized mice,
      irrespective of route of application. It significantly reduced blood glucose
      levels in glucose-primed mice, but it did not cause a dose dependent decrease of
      blood glucose level in healthy (nondiabetic, control) animals.

PMID- 7636867
TI  - Bisimidazoacridones and related compounds: new antineoplastic agents with high
      selectivity against colon tumors.
AB  - A new class of potent and highly selective antitumor agents has been synthesized.
      Bisimidazoacridones, where the tetracyclic ring systems are held together by
      either a N2-methyldiethylenetriamine or 3,3'-diamino-N-methyldipropylamine
      linker, and related asymmetrical compounds, where one of the imidazoacridone ring
      system was replaced by a triazoloacridone ring system, were found to be
      cytostatic and cytotoxic in vitro. Some of these compounds, such as 5,5'
      [(methylimino)bis(3,1-propanediylimino)]bis[6H-imidazo[ 4,5,1-de]acridin-6-one]
      (4b) showed remarkably high activity and selectivity for colon cancer in the
      National Cancer Institute screen. This antitumor effect was also apparent in
      colony survival assays utilizing the colon cancer line, HCT-116, and in in vivo
      assays involving xenografts of tumor derived from HCT-116 in nude mice. The
      tested compounds exhibited relatively low acute toxicity and were well-tolerated
      by the treated animals. The bisimidazoacridones interact with nucleic acids in
      vitro but preliminary experimental and modeling data indicate that in spite of
      their structure, they may not be bis-intercalators. While the precise mode of
      action of these compounds is not yet understood, they appear to be excellent
      candidates for clinical development.

PMID- 7636869
TI  - Synthesis and biological evaluation of a series of substituted
      benzo[a]phenanthridines as agonists at D1 and D2 dopamine receptors.
AB  - Dihydrexidine [4;(+/-)-trans-10,11-dihydroxy-5,6,6a,7,8, 12b
      hexahydrobenzo[a]phenanthridine (DHX)], the first high-affinity full D1 agonist,
      also is known to have significant D2 activity. The present work reports the
      synthesis and pharmacological activity of a series of analogs substituted in the
      pendent phenyl ring (i.e., 2-, 3-, or 4-position). (+/-)-trans-2-Methyl-10,11
      dihydroxy-5,6,6a,7,8, 12b-hexahydrobenzo[a]phenanthridine (5) was a high-affinity
      D1 agonist, having approximately 4-fold greater D1 vs D2 selectivity than DHX
      itself. All of the analogs containing a methyl or ethyl (but not a phenyl)
      substituent at the 2-, 3-, or 4-position had a pharmacological profile similar to
      that of the lead compound DHX (4). Each analog was found to be a high-affinity
      full agonist with moderate selectivity for the D1 receptor. It is apparent from
      these results that the D1 receptor can tolerate small substituents at the 2-, 3-,
      and 4-positions of the pendent phenyl ring. On the basis of earlier studies
      showing that N-alkylation increases D2 selectivity, the 3-methyl N-n-propyl and 4
      methyl N-n-propyl compounds 11 and 13 were synthesized. While these analogs
      exhibited much higher affinity for the D2 receptor, surprisingly 4-methyl-N
      propyl-DHX (13) exhibited high affinity for both the D1 and D2 receptors. It was
      subsequently established that this compound is a selective D3 ligand (110-fold
      selectivity for the D3 over D2 receptor). The results from these studies
      demonstrate that several of the hexahydrobenzo[a]phenanthridine derivatives are
      agonists with high intrinsic activity that may serve as powerful tools to explore
      the structural features that determine affinity and selectivity (relative to the
      D2 receptor) of drugs for D1 receptors.

PMID- 7636868
TI  - Diamine and triamine analogs and derivatives as inhibitors of deoxyhypusine
      synthase: synthesis and biological activity.
AB  - Deoxyhypusine synthase catalyzes the initial step in the posttranslational
      formation of the amino acid hypusine [N epsilon-(4-amino-2-hydroxybutyl)lysine]
      in eukaryotic initiation factor 5A (eIF-5A). eIF-5A and its hypusine modification
      are believed to be essential for cell growth. A number of compounds related to
      diamines and triamines were synthesized and tested as inhibitors of this enzyme.
      The findings indicate that the long chain triamines 2a and 2b and their guanyl
      derivatives 3a, 3b, 4a, and 4b exert inhibition by binding to enzyme through only
      a portion of their structures at any one time. The inhibition exhibited by N
      ethyl-1,7-diaminoheptane 20 and its guanyl derivative 21 supports this notion and
      is evidence for participation of the secondary amino group in binding to enzyme.
      There is preliminary evidence that amidino and isothiuronium groups may also
      serve as basic centers for binding to enzyme. Few of the compounds tested here
      were comparable in inhibitory potency to 1-guanidino-7-aminoheptane (GC7) the
      most effective known inhibitor of deoxhypusine synthase, and none proved nearly
      as efficient as GC7 in inhibiting the enzyme in Chinese hamster ovary cells.
      Hence, unlike the antiproliferative effect of GC7, for which there is evidence of
      cause by interference with deoxhypusine synthase catalysis (Park, M. H.; Wolff,
      E. C.; Lee, Y. B.; Folk, J. E. J. Biol. Chem. 269, 1994, 27827-27832), the
      effective growth arrest exerted by several of the newly synthesized compounds
      cannot be attributed to inhibition of hypusine synthesis.

PMID- 7636870
TI  - Synthesis and biological evaluation of 14-alkoxymorphinans. 11. 3
      Hydroxycyprodime and analogues: opioid antagonist profile in comparison to
      cyprodime.
AB  - A series of 3-hydroxy-substituted analogues (3-7) of the mu selective opioid
      antagonist cyprodime has been synthesized in order to evaluate the role of a
      hydroxy group at C-3 concerning mu opioid antagonist selectivity. Compounds 3-7
      were tested in bioassays (electrical stimulated mouse vas deferens preparation
      and myenteric-plexus longitudinal muscle preparation of the guinea pig ileum) and
      opioid receptor binding assays. Antagonism of mu receptor-mediated responses
      induced by the mu selective agonist DAMGO afforded equilibrium dissociation
      constants in the mouse vas deferens preparation (Ke values) for compounds 3-7
      which agreed closely with their affinities as determined by opioid receptor
      binding assays (Ki values). At kappa and delta receptors differences were
      apparent. Although the compounds had high affinity for both kappa and delta
      receptors in opioid receptor binding, they were very poor at antagonizing agonist
      responses mediated by kappa and particularly delta agonists in the mouse vas
      deferens preparation. None of the compounds tested showed agonist potency in the
      mouse vas deferens preparation or the myenteric-plexus longitudinal muscle
      preparation of the guinea pig ileum.

PMID- 7636871
TI  - Aziridine analogs of [[trans-(epoxysuccinyl)-L-leucyl]amino]-4-guanidinobutane (E
      64) as inhibitors of cysteine proteases.
AB  - Aziridine derivatives of E-64 have been synthesized, and their characterization
      against the cysteine proteases cathepsin B, cathepsin L, and papain is reported.
      The inhibition was found to be strongly pH-dependent, with maximum activity
      observed at pH 4, indicating that the protonated aziridinium ion form of the
      inhibitor is the more reactive form. At low pH, the peptide aziridine HO-(L)Az
      Leu-NH-iAm inactivated papain with a second-order rate constant, kinac/Ki, of 7.0
      x 10(4) M-1 s-1, a value very close to that observed with E-64 or with the
      corresponding epoxysuccinyl analog HO-(L)Eps-Leu-NH-iAm. This demonstrates that
      with the correct peptide sequence, aziridine analogs of E-64 can be good
      irreversible inhibitors of cysteine proteases. Substitution of the epoxysuccinyl
      moiety by an aziridine does not affect the specificity of inhibition against the
      three proteases used in this study. The D-diastereomer is the preferred (by 10
      fold) diastereomer for the inhibition of cysteine proteases. The reactivity of
      both diastereomers of iBuNH-Az-LeuPro-OH against cathepsin B was also found to be
      much lower than that of iBuNH-(L)Eps-LeuPro-OH, which is a potent selective
      inhibitor of cathepsin B. These differences are attributed mainly to the presence
      of the protonated aziridine ring, which can modify the binding mode of aziridine
      analogs at the active site of cysteine proteases.

PMID- 7636872
TI  - Chemistry and biology of the 2 beta-alkyl-3 beta-phenyl analogues of cocaine:
      subnanomolar affinity ligands that suggest a new pharmacophore model at the C-2
      position.
AB  - A series of 2 beta-alkyl-3 beta-phenyltropanes (i.e., the 2 beta-alkyl analogues
      of the WIN series) were prepared as analogues of cocaine and tested for their
      ability to displace [3H]mazindol binding and to inhibit high-affinity dopamine
      uptake into striatal nerve endings (synaptosomes). These 2 beta-alkyl analogues
      were readily prepared in optically pure form starting from cocaine by proceeding
      through the 2 beta-phenyl-bearing aldehyde 6 as a key intermediate. Wittig
      reaction of 6 with the appropriate phosphorane and hydrogenation delivered the
      final products. All new compounds with the exception of 8e were found to exhibit
      nanomolar or subnanomolar affinity for the cocaine binding site in the rat
      striatum. These results are in apparent opposition to the binding model
      previously proposed which suggests a hydrogen bond donor-acceptor interaction to
      be present in the vicinity of the C-2 substituent. Taken together with our
      previous reports and recent findings from other laboratories, we suggest a new
      pharmacophore model in which 2 beta-substituents lacking H-bond acceptors enhance
      affinity to the binding site through hydrophobic interactions. The new SAR data
      contained herein may be relevant to the design of possible cocaine antagonists.

PMID- 7636873
TI  - Aminoalkylindoles: structure-activity relationships of novel cannabinoid
      mimetics.
AB  - Aminoalkylindoles (AAIs) are a novel series of cannabinoid receptor ligands. In
      this report we disclose the structural features of AAIs which are important for
      binding to this receptor as measured by inhibition of binding of [3H]Win 55212-2
      (5). Functional activity in the mouse vas deferens is also noted and used to
      distinguish agonists from potential antagonists. The key structural features for
      potent cannabinoid activity in this series are a bicyclic (naphthyl) substituent
      at the 3-position, a small (H) substituent at the 2-position, and an aminoethyl
      (morpholinoethyl) substituent at the 1-position. A 6-bromo analog, Win 54461
      (31), has been identified as a potential cannabinoid receptor antagonist.
      Modeling experiments were done to develop a pharmacophore and also to compare AAI
      structures with those of classical cannabinoids. The fact that the cannabinoid
      AAIs arose out of work on a series of cyclooxygenase inhibitors make sense now
      that an endogenous cannabinoid ligand has been identified which is a derivative
      of arachidonic acid. Because of their unique structures and physical properties,
      AAIs provide useful tools to study the structure and function of the cannabinoid
      receptor(s).

PMID- 7636874
TI  - On the quantitative structure-activity relationships of meta-substituted (S)
      phenylpiperidines, a class of preferential dopamine D2 autoreceptor ligands:
      modeling of dopamine synthesis and release in vivo by means of partial least
      squares regression.
AB  - The quantitative structure-activity relationship between physicochemical
      properties and effects on dopamine (DA) synthesis and release in the rat brain,
      in a series of meta-substituted (S)-phenylpiperidines, has been investigated by
      means of partial least squares regression (PLS). The effect on DA synthesis
      caused by the drugs, in both non-pretreated and reserpine-pretreated rats, was
      assessed by measurements of tissue levels of L-DOPA accumulated in the striatum
      following treatment with a decarboxylase inhibitor. Assessment of effects on DA
      release was performed by analysis of perfusates collected from implanted
      microdialysis probes. The numerical characterization of the variation in
      physicochemical features of the phenylpiperidines used in the regression modeling
      was accomplished by using common tabulated aromatic and aliphatic substituent
      constants in combination with a set of property descriptors derived from
      molecular mechanics and semiempirical calculations. It was found that the
      biochemical responses could be accurately predicted by the regression models
      based on these molecular feature measures. The molecular features exerting
      influence on DA synthesis were found to be markedly different from those
      influencing DA release. This finding is discussed in terms of the possible
      existence of a dopamine receptor-mediated DA release-controlling mechanism, which
      may not involve the synthesis regulating DA D2 autoreceptor. Some findings
      regarding the impact of the piperidine N substituent on agonist properties of the
      drugs are reported. The regression models were also used for guidance in the
      search for a phenylpiperidine with a lower intrinsic activity, at the DA D2 type
      autoreceptor, than the partial DA agonist preclamol (3).

PMID- 7636875
TI  - Synthesis and dopaminergic activity of pyridine analogs of 5-hydroxy-2-(di-n
      propylamino)tetralin.
AB  - The pyridine analogs of 5-hydroxy-2-(di-n-propylamino)tetralin (5-OH-DPAT), 4-6,
      were synthesized, and their biological activity was compared to that of 5-OH
      DPAT. Compounds 4 and 6 exhibited activity similar to 5-OH-DPAT in dopamine (DA)
      D2 and D3 receptor binding and in autoreceptor activation as measured by their
      ability to reverse the gamma-butyrolactone-induced increase in rat DA synthesis.
      Behaviorally, 4 and 6 decreased locomotor activity (LMA) in rats (sc) at low
      doses but did not increase LMA to the same extent as 5-OH-DPAT at higher doses,
      indicating that 4 and 6 may be more selective for the DA autoreceptor. While 4
      was less active orally in rats, 6 appeared to retain most of its behavioral
      potency. Analog 5 showed little activity in vivo or in vitro.

PMID- 7636876
TI  - (1S,2S)-1-(4-hydroxyphenyl)-2-(4-hydroxy-4-phenylpiperidino)-1-propanol: a potent
      new neuroprotectant which blocks N-methyl-D-aspartate responses.
AB  - (1S,2S)-1-(4-Hydroxyphenyl)-2-(4-hydroxy-4-phenylpiperidino)-1-propanol (20, CP
      101,606) has been identified as a potent and selective N-methyl-D-aspartate
      (NMDA) antagonist through a structure activity relation (SAR) program based on
      ifenprodil, a known antihypertensive agent with NMDA antagonist activity. Sites
      on the threo-ifenprodil skeleton explored in this report include the pendent
      methyl group (H, methyl, and ethyl nearly equipotent; propyl much weaker), the
      spacer group connecting the C-4 phenyl group to the piperidine ring (an
      alternating potency pattern with 0 and 2 carbon atoms yielding the greatest
      potency), and simple phenyl substitution (little effect). While potent NMDA
      antagonists were obtained with a two atom spacer, this arrangement also increased
      alpha 1 adrenergic affinity. Introduction of a hydroxyl group into the C-4
      position on these piperidine ring resulted in substantial reduction in alpha 1
      adrenergic affinity. The combination of these observations was instrumental in
      the discovery of 20. This compound potently protects cultured hippocampal neurons
      from glutamate toxicity (IC50 = 10 nM) while possessing little of the undesired
      alpha 1 adrenergic affinity (IC50 approximately 20 microM) of ifenprodil.
      Furthermore, 20 appears to lack the psychomotor stimulant effects of nonselective
      competitive and channel-blocking NMDA antagonists. Thus, 20 shows great promise
      as a neuroprotective agent and may lack the side effects of compounds currently
      in clinical trials.

PMID- 7636877
TI  - Design and synthesis of potent retinoid X receptor selective ligands that induce
      apoptosis in leukemia cells.
AB  - Structural modifications of the retinoid X receptor (RXR) selective compound 4-[1
      (3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2- naphthyl)ethenyl]benzoic acid
      (LGD1069), which is currently in phase I/IIA clinical trials for cancer and
      dermatological indications, have resulted in the identification of increasingly
      potent retinoids with > 1000-fold selectivity for the RXRs. This paper describes
      the design and preparation of a series of RXR selective retinoids as well as the
      biological data obtained from cotransfection and competitive binding assays which
      were used to evaluate their potency and selectivity. The most potent and
      selective of the analogs is 6-[1-(3,5,5,8,8-pentamethyl-5,6,7,8
      tetrahydronaphthalen-2- yl)cyclopropyl]nicotinic acid (12d; LG100268). This
      compound has proven useful for investigating RXR dependent biological pathways
      including the induction of programmed cell death (PCD) and transglutaminase
      (TGase) activity. Our studies indicate that the induction of PCD and TGase in
      human leukemic myeloid cells is dependent upon activation of RXR-mediated
      pathways.

PMID- 7636878
TI  - Synthesis and biological evaluation of radioiodinated phospholipid ether
      stereoisomers.
AB  - Radioiodinated phospholipid ethers have shown the remarkable ability to
      selectively accumulate in a variety of animal tumors as well as in human tumor
      xenografts. It has been suggested that this tumor avidity may arise as a
      consequence of metabolic differences between tumor and corresponding normal
      tissue. One such compound, 1-O-[12-(m-iodophenyl)dodecyl]-2-O-methyl-rac-glycero
      3-phosphocholine (NM-294), contains a chiral center at the sn-2 position. The
      unnatural S- and natural R-enantiomers (4 and 5, respectively) of NM-294 were
      synthesized in order to provide further information on the mechanism(s)
      responsible for the tumor avidity of phospholipid ethers. In vitro cytotoxicity
      studies demonstrated a lack of stereospecificity. Biodistribution studies in rats
      bearing the Walker 256 tumor demonstrated the S- and R-isomers to have similar
      tissue uptake at 24 and 48 h after administration. Tumor-to-blood ratios at 24 h
      were 11.1 and 11.0 for the S- and R-isomers, respectively. In addition, gamma
      camera scintigrams of tumor-bearing rats at various time points after iv
      administration of the S- and R-isomers did not show any qualitative differences
      in the distribution of radioactivity. Prior studies have shown that rac-NM-294
      was not a substrate for phosphatidylcholine specific phospholipase C, but was a
      substrate for two forms of phospholipase D (PLD). Therefore, metabolism studies
      with 4 and 5 with various forms of PLD were performed. PLD from cabbage
      demonstrated a degree of stereoselectivity. In the presence of 1% ethanol, the R
      isomer was metabolized to the greatest extent, followed by rac-NM-294 and the S
      isomer. PLD isolated from Streptomyces chromofuscus failed to demonstrate any
      stereoselectivity. The results suggest that the mechanism(s) of retention of
      these compounds in tumors may not involve a highly stereoselective component.

PMID- 7636880
TI  - Potent inhibitors of acyl-CoA:cholesterol acyltransferase. Structure-activity
      relationships of novel N-(4-oxochroman-8-yl)amides.
AB  - Novel N-(4-oxochroman-8-yl)amide derivatives 1 were synthesized and tested for
      their ability to inhibit rabbit small intestinal ACAT (acyl-CoA:cholesterol
      acyltransferase) in vitro and to lower serum total cholesterol in cholesterol-fed
      rats in vivo. Among the synthesized compounds, N-(7-alkoxy-4-oxochroman-8
      yl)amide derivatives showed potent ACAT inhibitory activity both in vitro and in
      vivo. The structure-activity relationships of these N-(4-oxochroman-8-yl)amides
      and related compounds are discussed on the basis of these two assays. The
      carbonyl group at position 4 of the 4-chromanone was essential for potent ACAT
      inhibitory activity. N-(Chromon-8-yl) derivatives were less potent than N-(4
      oxochroman-8-yl) derivatives. An alkoxy group at position 7 of the 4-chromanone
      moiety was important for potent ACAT inhibitory activity. In the N-(7-alkoxy-4
      oxochroman-8-yl)amide derivatives, another necessary factor to elicit the potent
      ACAT inhibitory activity was lipophilicity of the molecules. The highly
      lipophilic acid amides N-(7-methoxy-4-oxochroman-8-yl)-2,2-dimethyldodecanamide
      (35) and 4-[[6-(4-chlorophenoxy)hexyl]oxy]-N-(7-methoxy-4-oxochroman-8-
      yl)benzamide (63) showed potent activity. Introduction of a highly lipophilic
      alkoxy group at position 7 of the 4-chromanone moiety instead of methoxy group
      also resulted in potent activity. In this case, highest inhibitory activity was
      obtained by N-[7-(decyloxy)-4-oxochroman-8-yl]-2,2-dimethylpropanamid e (65). The
      most potent compound, N-(7-methoxy-4-oxochroman-8-yl)-2,2-dimethyldodecanamide
      (35, TEI-6522), showed significant ACAT inhibitory activity (rabbit small
      intestine IC50 = 13 nM, rabbit liver IC50 = 16 nM), foam cell formation
      inhibitory activity (rat peritoneal macrophage IC50 = 160 nM), and extremely
      potent serum cholesterol-lowering activity in cholesterol-fed rats (61% at a dose
      of 0.1 mg/kg/day po).

PMID- 7636879
TI  - A novel type of retinoic acid receptor antagonist: synthesis and structure
      activity relationships of heterocyclic ring-containing benzoic acid derivatives.
AB  - A new series of heterocyclic ring-containing benzoic acids was prepared, and the
      binding affinity and antagonism of its members against all-trans-retinoic acid
      were evaluated by in vitro assay systems using human promyelocytic leukemia (HL
      60) cells. Structure-activity relationships indicated that both an N-substituted
      pyrrole or pyrazole (1-position) and a hydrophobic region, with these linked by a
      ring system, were indispensable for effective antagonism. Among the compounds
      evaluated, optimal antagonism was exhibited by 4-[4,5,7,8,9,10-hexahydro-7,7,10,
      10-tetramethyl-1-(3- pyridylmethyl)anthra[1,2-b]pyrrol-3-yl]benzoic acid (31), 4
      [4,5,7,8,9,10-hexahydro-7,7,10,10-tetramethyl-1-(3-pyridylmethyl)-5-
      thiaanthral[1,2-b]pyrrol-3-yl]benzoic acid (40), and 4-[4,5,7,8,9,10-hexahydro
      7,7,10,10-tetramethyl-1-(3- pyridylmethyl)anthra[2,1-d]pyrazol-3-yl]benzoic acid
      (55), all of which possess a 3-pyridylmethyl group at the five-membered ring
      nitrogen atom.

PMID- 7636881
TI  - Oligopeptide transport by epithelial cells.

PMID- 7636883
TI  - Responses of neurons to extreme osmomechanical stress.
AB  - Neurons are often regarded as fragile cells, easily destroyed by mechanical and
      osmotic insult. The results presented here demonstrate that this perception needs
      revision. Using extreme osmotic swelling, we show that molluscan neurons are
      astonishingly robust. In distilled water, a heterogeneous population of Lymnaea
      stagnalis CNS neurons swelled to several times their initial volume, yet had a
      ST50 (survival time for 50% of cells) > 60 min. Cells that were initially bigger
      survived longer. On return to normal medium, survivors were able, over the next
      24 hr, to rearborize. Reversible membrane capacitance changes corresponding to
      about 0.7 muF/cm2 of apparent surface area accompanied neuronal swelling and
      shrinking in hypo- and hyperosmotic solutions; reversible changes in cell surface
      area evidently contributed to the neurons' ability to accommodate hydrostatic
      pressures then recover. The reversible membrane area/capacitance changes were not
      dependent on extracellular Ca2+. Neurons were monitored for potassium currents
      during direct mechanical inflation and during osmotically driven inflation. The
      latter but not the former stimulus routinely elicited small potassium currents,
      suggesting that tension increases activate the currents only if additional
      disruption of the cortex has occurred. Under stress in distilled water, a third
      of the neurons displayed a quite unexpected behavior: prolonged writhing of
      peripheral regions of the soma. This suggested that a plasma membrane-linked
      contractile machinery (presumably actomyosin) might contribute to the neurons'
      mechano-osmotic robustness by restricting water influx. Consistent with this
      possibility, 1 mM N-ethyl-maleimide, which inhibits myosin ATPase, decreased the
      ST50 to 18 min, rendered the survival time independent of initial size, and
      abolished writhing activity. For neurons, active mechanical resistance of the
      submembranous cortex, along with the mechanical compliance supplied by insertion
      or eversion of membrane stores may account for the ability to withstand diverse
      mechanical stresses. Mechanical robustness such as that displayed here could be
      an asset during neuronal outgrowth or regeneration.

PMID- 7636882
TI  - Lipid-ion channel interactions: increasing phospholipid headgroup size but not
      ordering acyl chains alters reconstituted channel behavior.
AB  - We have recently shown (Chang et al., 1995) that lipid-channel interactions,
      exemplified by the effects of cholesterol on the calcium-activated potassium (BK)
      channel, profoundly affect channel properties. The present study further explores
      such interactions by monitoring changes in BK channel behavior after
      reconstitution into bilayers where the size of phospholipid (PL) headgroups is
      increased and where the freedom of motion (inverse order) of fatty acid chains is
      incremented. Increasing the PL headgroup cross-sectional area, from that of N
      meth-DOPE to that of DOPC (an increase from ca. 60 to 70 A2), is associated with
      a doubling of the channel mean opentime. Channel conductance, however, was
      unaffected. Increasing the order of the fatty acid chains, from that of DOPE to
      POPE and to that of DEPE, had no significant effect on channel properties (at 22
      degrees C). We interpret the changes reported here to reflect lipid-protein
      interactions through the induction of structural stress related to the headgroup
      structures of phospholipids.

PMID- 7636884
TI  - Discrete and reversible vacuole-like dilations induced by osmomechanical
      perturbation of neurons.
AB  - In cultured Lymnaea stagnalis neurons, osmolarity increases (upshocks) rapidly
      elicited large membranous dilations that could be dislodged and pushed around
      inside the cell with a microprobe. Subsequent osmolarity decreases (downshocks)
      caused these vacuole-like dilations (VLDs) to disappear. Additional
      upshock/downshock perturbations resulted in repeated appearance/disappearance
      (formation/reversal) of VLDs at discrete sites. Confocal microscopy indicated
      that VLDs formed as invaginations of the substrate-adherent surface of the
      neuron: extracellular rhodamine-dextran entered VLDs as they formed and was
      expelled during reversal. Our standard VLD-inducing perturbation was: 2-4 min
      downshock to distilled water, upshock to normal saline. However, a wide range of
      other osmotic perturbations (involving osmolarities up to 3.5 x normal,
      perturbations with or without Ca2+, replacement of ions by sucrose) were also
      used. We concluded that mechanical, not chemical, aspects of the osmo-mechanical
      shocks drove the VLD formation and reversal dynamics and that extracellular Ca2+
      was not required. Following a standard perturbation, VLDs grew from invisible to
      their full diameter (> 10 microns) in just over a minute. Over the next 0.5-3 hr
      in normal saline, neurons recovered. Recovery eliminated any visible VLDs and was
      accompanied by cytoplasmic turmoil around the VLDs. Recovery was prevented by
      cytochalasin B, brefeldin A and N-ethylmaleimide but not by nocodazole. In
      striking contrast, these drugs did not prevent repeated VLD formation and
      reversal in response to standard osmo-mechanical perturbations; VLD disappearance
      during reversal and during recovery are different. The osmo-mechanical changes
      that elicited VLDs may, in an exaggerated fashion, mimic tension changes in
      extending and retracting neurites. In this context we postulate: (a) the
      trafficking or disposition of membrane between internal stores and plasma
      membrane is mechanosensitive, (b) normally, this mechanosensitivity provides an
      "on demand" system by which neurons can accommodate stretch/release perturbations
      and control cell shape but, (c) given sudden extreme mechanical stimuli, it
      yields VLDs.

PMID- 7636885
TI  - NO3- transport across the plasma membrane of Arabidopsis thaliana root hairs:
      kinetic control by pH and membrane voltage.
AB  - High-affinity nitrate transport was examined in intact root hair cells of
      Arabidopsis thaliana using electrophysiological recordings to characterise the
      response of the plasma membrane to NO3- challenge and to quantify transport
      activity. The NO3(-)-associated membrane current was determined using a three
      electrode voltage clamp to bring membrane voltage under experimental control and
      to compensate for current dissipation along the longitudinal cell axis. Nitrate
      transport was evident in the roots of seedlings grown in the absence of a
      nitrogen source, but only 4-6 days postgermination. In 6-day-old seedlings,
      additions of 5-100 microM NO3- to the bathing medium resulted in membrane
      depolarizations of 8-43 mV, and membrane voltage (Vm) recovered on washing NO3-
      from the bath. Voltage clamp measurements carried out immediately before and
      following NO3- additions showed that the NO3(-)-evoked depolarizations were the
      consequence of an inward-directed current that appeared across the entire range
      of accessible voltages (-300 to +50 mV). Both membrane depolarizations and NO3(-)
      evoked currents recorded at the free-running voltage displayed quasi-Michaelian
      kinetics, with apparent values for Km of 23 +/- 6 and 44 +/- 11 microM,
      respectively and, for the current, a maximum of 5.1 +/- 0.9 muA cm-2. The NO3-
      current showed a pronounced voltage sensitivity within the normal physiological
      range between -250 and -100 mV, as could be demonstrated under voltage clamp, and
      increasing the bathing pH from 6.1 to 7.4-8.0 reduced the current and the
      associated membrane depolarizations 3- to 8-fold. Analyses showed a well-defined
      interaction between the kinetic variables of membrane voltage, pHo and [NO3-]o.
      At a constant pHo of 6.1, depolarization from -250 to -150 mV resulted in an
      approximate 3-fold reduction in the maximum current but a 10% rise in the
      apparent affinity for NO3-. By contrast, the same depolarization effected an
      approximate 20% fall in the Km for transport as a function in [H+]o. These, and
      additional characteristics of the transport current implicate a carrier cycle in
      which NO3- binding is kinetically isolated from the rate-limiting step of
      membrane charge transit, and they indicate a charge-coupling stoichiometry of
      2(H+) per NO3- anion transported across the membrane. The results concur with
      previous studies showing a high-affinity NO3- transport system in Arabidopsis
      that is inducible following a period of nitrogen-limiting growth, but they
      underline the importance of voltage as a kinetic factor controlling NO3-
      transport at the plant plasma membrane.

PMID- 7636887
TI  - ATP, pH and Mg2+ modulate a cation current in Beta vulgaris vacuoles: a possible
      shunt conductance for the vacuolar H(+)-ATPase.
AB  - Macroscopic instantaneous and time-dependent currents have been measured in the
      vacuolar membrane of Beta vulgaris using a patch clamp configuration analogous to
      whole cell mode. At low cytosolic Ca2+ and in the absence of Mg2+, only an
      instantaneous current was observed. This current is carried predominantly by
      cations (PK:PCl 7:1, PNa:PCl 4:1 and arginine is also conducted). The
      instantaneous current can be activated by ATP4- (e.g., ATP-activated mean K+
      current density was -20 mA.m-2 at a membrane voltage of -20 mV) and by increasing
      cytosolic pH and Mg2+ (raising Mg2+ from 0 to 0.4 mM induced a mean current
      density increase of -7 mA.m-2 at -20 mV). Such current can be activated by
      simultaneous addition of putative in vivo concentrations of ATP4-/MgATP/Mg2+free
      (in the presence of bafilomycin to inhibit the vacuolar ATPase) and further
      modulated by cytosolic pH. With vacuolar K+ concentration greater than that of
      the cytosol, activation of the instantaneous current would mediate vacuolar K+
      release over the range of physiological membrane voltage. It is argued that the
      ATP(4-)-activated current, in addition to acting as a K+ mobilization pathway,
      could provide a counter-ion (shunt) conductance, allowing the two electrogenic H+
      pumps which reside in the vacuolar membrane to acidify the vacuolar lumen. A
      separate time-dependent current, which was not observed at low Ca2+
      concentrations (less than 500 nM) could also be elicited by addition of Mg2+ at
      the cytoplasmic membrane face. This current was stimulated by increasing
      cytoplasmic pH.

PMID- 7636886
TI  - Renal cortical basolateral Na+/HCO3- cotransporter. III. Evidence for a
      regulatory protein in the inhibitory effect of protein kinase A.
AB  - The activity of the Na-H antiporter is inhibited by cyclic AMP-dependent protein
      kinase A (cAMP-PKA). The inhibitory effect of PKA on the Na-H antiporter is
      mediated through a regulatory protein that can be dissociated from the antiporter
      by limited protein digestion. PKA also inhibits the activity of the Na+/HCO3-
      cotransporter. We investigated whether the activity of Na+/HCO3- cotransporter
      and the effect of PKA on this transporter may also be regulated by limited
      protein digestion. In rabbit renal cortical basolateral membranes (BLM) and in
      solubilized BLM reconstituted in liposomes (proteoliposomes), trypsin (100
      micrograms) increased 22Na uptake in the presence of HCO3 but not in the presence
      of gluconate, indicating that trypsin does not alter diffusive 22Na uptake but
      directly stimulates the Na+/HCO3- cotransporter activity. In proteoliposomes
      phosphorylated with ATP, the catalytic subunit (CSU) of cAMP-PKA decreased the
      activity of the Na+/HCO3- cotransporter (expressed as nanomoles/mg protein/3s)
      from 23 +/- 10 to 14 +/- 6 (P < 0.01). In the presence of trypsin, the inhibitory
      effect of CSU of cAMP-PKA on the activity of Na+/HCO3- cotransporter was blunted.
      To identify a fraction that was responsible for the inhibitory effect of the CSU
      on the Na+/HCO3- cotransporter activity, solubilized proteins were separated by
      size exclusion chromatography. The effect of CSU of cAMP-PKA on the Na+/HCO3-
      cotransporter activity was assayed in proteoliposomes digested with trypsin with
      the addition of a fraction containing the 42 kDa protein (fraction S+) or without
      the 42 kDa protein (fraction S-).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7636888
TI  - Drug-transport and volume-activated chloride channel functions in human
      erythroleukemia cells: relation to expression level of P-glycoprotein.
AB  - The characteristics of volume-activated chloride currents, drug transport
      function and levels of P-glycoprotein (PgP) expression were compared between two
      human chronic erythroleukemia cell lines: a parental (K562) cell line and a
      derivative obtained by vinblastine selection (K562 VBL400). Parental K562 cells
      showed no detectable P-glycoprotein expression, measured at the protein level
      (immunofluorescence labeling with monoclonal antibodies), and had very low levels
      of MDR-1 mRNA expression (RT-PCR analysis), when compared with levels measured in
      K562 VBL400. Differences in Pgp-mediated transport were estimated by comparing
      the rates of Fluo3 accumulation. The higher drug-transport function of K562
      VBL400 cells (e.g., lower Fluo3 accumulation) correlated with their elevated
      levels of MDR-1. The rate of dye transport was sensitive to verapamil but was not
      affected by the tonicity of the extracellular medium. In contrast to the clear
      differences in transport function, the characteristics of chloride currents
      induced by cell swelling were indistinguishable between the two cell lines.
      Currents measured in the whole-cell configuration were outwardly rectifying, had
      a higher permeability to iodide than to chloride (SCN- > I- > Cl- > gluconate),
      were potently blocked by NPPB and were unresponsive to verapamil. The percentage
      of responding cells and the mean current density were nearly identical in both
      cell lines. In addition, activation of the volume-sensitive current was not
      prevented during whole-cell recordings obtained with pipettes containing high
      concentration of cytotoxic drugs (vincristine or vinblastine). These results do
      not lend support to the previously reported association between Pgp expression
      and volume-sensitive chloride channels, and suggest that a different protein is
      responsible for this type of chloride channel in K562 cells.

PMID- 7636890
TI  - State health-care reform: issues and concerns.

PMID- 7636889
TI  - Synergistic action of vasopressin and aldosterone on basolateral Na(+)-K(+)
      ATPase in the cortical collecting duct.
AB  - The respective effects of aldosterone and arginine vasopressin (AVP) were
      examined on the number of active Na(+)-K(+)-ATPase and their pumping activity in
      nonperfused microdissected mouse cortical collecting tubules (CCD) by measuring
      specific 3H-ouabain binding and ouabain-sensitive 86Rb uptake. In
      adrenalectomized (ADX) animals, incubation of CCD with AVP (10(-8) M for 5 min)
      had no effect on the number of pumps. In contrast, in ADX animals replete with
      aldosterone, AVP induced a approximately equal to 40% increase in the number of
      pumps. This was accompanied by a approximately equal to 60-65% increase in
      ouabain-sensitive Rb uptake. AVP effect was dose-dependent (10(-10)-10(-8) M) and
      was reproduced by dDAVP, forskolin and 8-Br cAMP, indicating a V2 pathway. It was
      inhibited by amiloride 10(-5) M, and did not occur in CCD incubated in
      hyperosmotic solution, suggesting that the signal was transmitted via apical
      sodium entry and cell swelling. Finally, the AVP-dependent increase in the number
      of pumps was rapid (within 5 min) and transient (< 25 min). These results
      demonstrate that, in the CCD, aldosterone and AVP act synergistically to increase
      not only the apical sodium entry but also the basolateral Na(+)-K(+)-ATPase
      transport capacity: AVP allows a rapid recruitment and/or activation of an
      aldosterone-dependent pool of latent Na(+)-K(+)-ATPase.

PMID- 7636891
TI  - Alternative medicine: "new" treatment for the 1990s.

PMID- 7636893
TI  - Allopurinol improves myocardial reperfusion injury in a xanthine oxidase-free
      model.
AB  - The ability of allopurinol to protect against reperfusion injury in the heart has
      usually been attributed to its xanthine oxidase (XO)-inhibiting properties. Human
      myocardium however, has exhibited low levels of XO activity. To investigate the
      effects of allopurinol in an XO-free model and determine whether pretreatment is
      necessary, 12 domestic pigs (15 kg to 20 kg) underwent occlusion of the left
      circumflex for 8 minutes followed by reperfusion for 4 hours. One group received
      allopurinol infusion (5 mg/kg IV) at occlusion over 45 minutes and a control
      group (n = 6) received a saline infusion (same volume). Left ventricular and
      aortic pressure, electrocardiograms, and regional wall motion (sonomicrometry)
      were monitored throughout the process. Regional blood flow (microspheres) were
      obtained before, during, and 5, 10, and 30 minutes after ischemia. Occlusion
      decreased transmural flow at the midpapillary level by 75% (0.28 versus 1.10
      mL/minute/g). The allopurinol-treated group exhibited a mild, generalized
      hyperemia at 5 minutes (ischemic zone: 1.44 versus 1.10 mL/min/g, which returned
      to control levels at 10 and 30 minutes. In contrast, the control group was
      associated with only 80% restoration of resting blood flow at 5 minutes (0.84
      versus 1.10 mL/min/g), which stabilized at 63% of control levels at 10 and 30
      minutes. When evaluated for the propensity of arrhythmias using an arbitrary
      arrhythmia score, the allopurinol group demonstrated no myocardial ectopy when
      compared with the focal ectopy routinely encountered in the control group at all
      time intervals.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7636892
TI  - Characteristics of black Medicaid elderly and their access to postacute care.
AB  - The delivery and financing of health-care services are among the nation's most
      debated issues. Policymakers, providers, and the government are challenged to
      improve access to medical services for those who are underserved and in need.
      This study examines the characteristics of underserved black elderly patients and
      the components that contribute to their long-stay status. The findings suggest
      that black elderly patients suffer a variety of illnesses that confine them to
      longer stays in the hospital. Controlling health-care costs will be difficult
      unless barriers to postacute care services are eliminated for poor, minority,
      elderly patients. As health reform strategies are developed, consideration should
      be given to policies and models that improve access to postacute care.

PMID- 7636894
TI  - The efficacy and tolerability of amlodipine and hydrochlorothiazide in Nigerians
      with essential hypertension.
AB  - The efficacy and safety of the novel calcium antagonist Amlodipine (Pfizer
      Laboratories, New York, New York) and hydrochlorothiazide were evaluated and
      compared in a randomized, single-blind, parallel group study in black Africans
      with essential hypertension. Twenty Nigerians with newly diagnosed mild to
      moderate essential hypertension were randomized to receive ascending doses of
      Amlodipine (5 mg and 10 mg) or hydrochlorothiazide (25 mg or 50 mg), and blood
      pressure and heart rate were measured at baseline and at 2, 4, and 6 weeks of
      therapy. Both Amlodipine and hydrochlorothiazide significantly reduced supine and
      erect blood pressure. Supine blood pressure on Amlodipine fell from a mean of
      190/104 mm Hg to 150/79 mm Hg, and on thiazide from 180/103 mm Hg to 141/84 mm
      Hg. There was, however, no significant difference between both drugs in
      antihypertensive efficacy. Neither drug induced a reflex increase in heart rate.
      The fall in blood pressure on both agents was associated with an increase in
      plasma urea. Amlodipine induced no change in plasma potassium, but
      hydrochlorothiazide caused hypokalemia. Both agents were well tolerated, and
      Amlodipine should undergo further study in the treatment of hypertension in
      blacks.

PMID- 7636895
TI  - The anatomy of the brachial plexus as displayed by magnetic resonance imaging:
      technique and application.
AB  - Full field of view coronal chest magnetic resonance imaging (MRI) routinely
      displays bilateral images of the brachial plexus, surface anatomy, and anatomic
      structures. Eighty patients had chest radiographs correlated with surgery for
      thoracic outlet syndrome. The PA chest film findings correlated with the surgical
      findings: smaller thoracic inlet on the concave side of the cervicothoracic spine
      scoliosis, shorter distance between the dorsal spine of the second or third
      thoracic vertebral body to the concavity of the first ribs, asymmetric clavicles
      and coracoid processes, synchondrosis of the first and second ribs, and muscle
      atrophy on the side of the clinical complaints. More than 235 patients were
      imaged. One hundred sixty-five of these were imaged with a 1.5-T unit and 3-D
      reconstruction MRI. Coronal, transverse (axial), oblique transverse, and sagittal
      plane T1-weighted, selected T2-weighted, and fast spine echo pulse sequences were
      obtained, 4- to 5-mm slice thickness, 40 to 45 cm full field of view, 512 x 256
      matrix and 2 NEX. Two-dimensional time of flight (2D TOF), magnetic resonance
      angiography (MRA) sequences were obtained in selected patients. Coronal,
      transverse, and sagittal sequences were reformatted for evaluation. Saline water
      bags were placed between the neck and thorax to enhance the signal-to-noise
      ratio. Compromising abnormalities of the brachial plexus were confirmed at
      surgery. Compromise of the neurovascular supply seemed to be one etiology that
      could be demonstrated. The clinical history, technique, and anatomic bilateral
      brachial plexus imaging is stressed to improve patient care. The cervical rib is
      one of the compromising brachial plexopathies selected for this presentation.

PMID- 7636896
TI  - Conservative treatment of early-stage breast cancer in a medically indigent
      population.
AB  - The compliance with a program of breast-conservation treatment for early-stage
      breast cancer and the results of that treatment among women treated between
      January 1983 and January 1992 was investigated in a large inner-city public
      hospital serving a primarily black population. Medical records and charts were
      reviewed for 25 consecutive patients with stage I and II breast cancer seen in
      consultation in the radiation oncology department. Of those 25 patients, 20
      underwent lumpectomy and radiation therapy. Survival, disease-free survival, and
      local recurrence-free survival were computed using the Kaplan-Meier method.
      Compliance was evaluated based on time to complete the prescribed course of
      radiotherapy after a lumpectomy. Five-year local recurrence-free survival for
      stage I and II patients was 95% (confidence interval [CI]: 71% to 99%). Five-year
      overall survival for stage II patients was 71% (CI: 31% to 92%), and disease-free
      survival was 74% (CI: 36% to 91%). This study demonstrates that a program of
      breast-conservation treatment for early-stage breast cancer can be implemented
      with good results, excellent treatment compliance, and 100% follow-up in a
      population of medically indigent women.

PMID- 7636897
TI  - The value of X rays. 1911.

PMID- 7636898
TI  - Tumor necrosis factor-induced necrosis: a monocyte-mediated hypercoagulable
      effect.
AB  - The mechanisms by which tumor necrosis factor (TNF) exerts its necrotic effects
      are somewhat obscure. We hypothesize that TNF, by monocyte activation, produces
      the procoagulant tissue factor, thus leading to a state of hypercoagulability
      with resultant thrombotic vascular occlusion and tissue necrosis. To test this
      hypothesis, modified recalcification time values (in minutes +/- standard
      deviation) were obtained on aliquots of blood with A) 20 microL of albumin, B) 20
      microL of saline containing endotoxin, and C) 20 microL of albumin with 450 units
      of TNF. No differences were noted if the samples were not incubated. We conclude
      that TNF, can cause tumor (tissue) necrosis, and since incubation is required,
      TNF alone (without monocyte activation) has no procoagulant activity.

PMID- 7636899
TI  - Trauma systems, trauma centers, and trauma surgeons: opportunity in managed
      competition.

PMID- 7636900
TI  - Polymicrobial sepsis following trauma inhibits interleukin-10 secretion and
      lymphocyte proliferation.
AB  - Immune competence declines following major injury, and predisposes the trauma
      patient to infection. Interleukin-10 (IL-10), although an immunosuppressive
      cytokine, is also important in the initiation of immune responses. This study
      investigated alterations in IL-10 and immune function associated with
      polymicrobial sepsis following trauma using murine femur fracture (FFx) and cecal
      ligation/puncture (CLP) models. Mice were randomized to Normal, FFx, Alcohol and
      FFx (EtOH + FFx), CLP, FFx + CLP, and EtOH + FFx + CLP. Polymicrobial sepsis was
      induced by performing CLP 4 days after FFx, and animals were killed 14 days
      later; immune function was assessed by in vitro splenocyte cultures. Lymphocyte
      proliferative responses were significantly suppressed in FFx and CLP animals.
      Splenocyte IL-10 production was significantly reduced in FFx and CLP animals,
      with concurrent increases in nitrite and tumor necrosis factor release. This
      study documents that trauma induces alterations in the inflammatory cytokine
      cascade that affect the immune response to subsequent septic challenges.

PMID- 7636901
TI  - Soluble cytokine receptors and receptor antagonists are sequentially released
      after trauma.
AB  - Cytokine receptors and receptor antagonists (RAs) have been identified in trauma
      patients. We hypothesized that after traumatic injury, a sequential release of
      soluble cytokine receptors and RAs may exist that mirrors the release of the
      primary cytokines themselves. Twenty-two patients were included in the study: 14
      males and 8 females. The mean age was 30.1 +/- 12.5 (range, 19 to 71), and the
      mean Injury Severity Score was 28.7 +/- 12.6 (range, 4 to 57). There were 15
      survivors and 7 nonsurvivors. Samples were collected on arrival to the emergency
      department and at serial intervals for up to 7 days. Monoclonal antibody enzyme
      linked immunosorbent assay kits to tumor necrosis factor (TNF), soluble TNF
      receptor (sTNF-R) 55 kd and 75 kd, interleukin (IL)-1 and IL-1 RA, and IL-2 and
      IL-2r were used. Sera from 22 healthy individuals were used as normal controls.
      No TNF, IL-1, or IL-2 could be detected in any patient sera after injury. Control
      levels for the soluble cytokine receptors and RAs were as follows: sTNF-R 55 kd,
      607 +/- 89 pg/mL; sTNF-R 75 kd, 2,141 +/- 169 pg/mL; IL-1 RA, 291 +/- 35 pg/mL;
      and IL-2r, 426 +/- 53 U/mL. In trauma patients, both 55 kd and 75 kd sTNF-R were
      significantly elevated on arrival to the emergency department, with values of
      2,441 +/- 506 pg/mL (p < 0.001) and 4,736 +/- 537 pg/mL (p < 0.001),
      respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7636902
TI  - Death from severe trauma: open fractures to multiple organ dysfunction syndrome.

PMID- 7636903
TI  - Pentoxifylline attenuates the depressed endothelial cell function and vascular
      muscle contractility following trauma and hemorrhagic shock.
AB  - Although pentoxifylline (PTX) produces various beneficial effects following
      adverse circulatory conditions, it is not known whether this agent attenuates the
      depressed vascular endothelial cell function [i.e., the reduced release of
      endothelium-derived nitric oxide (EDNO)] and smooth muscle contractility after
      trauma and hemorrhage. To study this, rats underwent a midline laparotomy (i.e.,
      trauma induced) and were bled to and maintained at a mean arterial pressure of 40
      mm Hg until 40% of maximal shed volume was returned in the form of lactated
      Ringer's solution. The animals were then resuscitated with 4 times the volume of
      maximal bleedout with lactated Ringer's solution, following which PTX (50 mg/kg
      body weight), or an equivalent volume of normal saline, was infused intravenously
      over 95 minutes. At 1.5 hours after resuscitation, the aorta was isolated and
      studied in vitro. Norepinephrine-induced vascular contraction and dose responses
      for acetylcholine (ACh), an endothelium-dependent vasodilator, were then
      determined. The results indicate that the decreased ACh-induced relaxation in
      hemorrhaged animals was restored with PTX treatment. Moreover, the increased ACh
      IC50 values (ACh concentration that causes half-maximum relaxation) after
      hemorrhage were reduced by PTX. In contrast, there was no significant difference
      in the relaxation induced by an endothelium-independent vasodilator,
      nitroglycerine, in the tested groups. Thus, PTX restores a hemorrhage-induced
      decrease in endothelium-derived nitricoxide production. In addition, the
      depressed smooth muscle contractile function was also attenuated by PTX
      treatment. Because PTX restored the depressed endothelial cell function and
      smooth muscle contractility, this agent appears to be a useful adjunct to fluid
      resuscitation for the management of trauma and hemorrhage.

PMID- 7636905
TI  - Transesophageal echocardiography for the initial evaluation of the widened
      mediastinum in trauma patients.
AB  - Traumatic disruption of the thoracic aorta is an injury that is rapidly fatal if
      not recognized and treated early. Increasingly, transesophageal echocardiography
      (TEE) is being used to evaluate the thoracic aorta after trauma with reported
      sensitivity and specificity rates of up to 100%. To confirm these results, we
      instituted a protocol using TEE as the initial diagnostic study for excluding a
      ruptured thoracic aorta in patients with widened mediastinum. All TEE studies
      were done by experienced cardiologists; 96% were done in the trauma receiving
      area. TEE studies were classified as positive, negative, or indeterminant.
      Indeterminant studies were those in which the diagnosis of aortic injury could
      not be excluded based solely on TEE findings. Because we were interested in using
      TEE as a "definitive" diagnostic modality, indeterminant studies were regarded as
      positive for our analysis. This protocol was used in 114 trauma patients over a 3
      year period. TEE identified five thoracic aortic disruptions--three confirmed by
      aortography and two by thoracotomy. TEE was read as indeterminant in 17 patients
      and further investigation with aortography showed no aortic injury in these
      patients. TEE was negative in 89 patients who had no further evaluation and were
      subsequently discharged or who died from other injuries. TEE failed to reveal
      significant lesions in three patients who had aortograms that revealed
      disruptions requiring thoracotomy. The use of TEE for the definitive diagnosis of
      ruptured aorta in this series yields a sensitivity of 63% and a specificity of
      84%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7636906
TI  - CD11b blockade prevents lung injury despite neutrophil priming after gut
      ischemia/reperfusion.
AB  - Gut ischemia/reperfusion (I/R) provokes lung injury via a mechanism that involves
      neutrophils [polymorphonuclear neutrophils (PMNs)]. CD11b/CD18 (alpha mB2) is the
      integrin receptor on PMNs critical for adhesion-dependent oxidative burst. The
      purpose of this study was to investigate the mechanistic role of CD11b in the
      process of gut I/R-induced lung injury. Sprague-Dawley rats underwent 45 minutes
      of superior mesenteric artery (SMA) occlusion with and without CD11b monoclonal
      antibody treatment (IB6) (1 mg/kg, i.v.), before SMA clamping. At 2-hour
      reperfusion, PMN presence in tissue was quantitated by myeloperoxidase activity
      and circulating PMN priming determined by the difference in superoxide production
      with and without N-formyl-methionyl-leucyl-phenylalanine, whereas lung leak was
      assessed by 125I-albumin lung/blood ratio. In sum, CD11b blockade prevented gut
      I/R-induced lung leak, but did not attenuate gut I/R-induced PMN priming or
      tissue PMN accumulation. In conclusion, gut I/R promotes PMN priming and PMN
      adhesion in both local and distant beds via receptors other than CD11b, but this
      B2 integrin receptor is critical for PMN-mediated endothelial injury.

PMID- 7636907
TI  - Injury prevention strategies to promote helmet use decrease severe head injuries
      at a level I trauma center.
AB  - Head injuries (HIs) remain a major contributor to trauma mortality, with many
      deaths occurring despite optimal use of available therapy. Injury prevention is
      vital to decrease the impact of HIs. Helmets can decrease the severity of HIs in
      both bicycle crashes (BCs) and motorcycle crashes (MCCs). A major challenge is to
      increase helmet use. A mandatory motorcycle helmet law in 1990 and information
      campaigns aimed at bicyclists have increased the percentage of riders wearing
      helmets in Washington State. We hypothesized that there would be an associated
      decrease in the proportion of severe HIs in BC and MCC admissions to the state's
      only level I trauma center. We analyzed injury region and outcomes for all 466 BC
      and 992 MCC instate admissions from 1986 to 1993. For BCs, the proportion of
      severe HIs (Abbreviated Injury Scale score of 4 or 5) declined from 29% in 1986
      to 11% in 1993 (p = 0.02). BC trends paralleled helmet use in observations on
      8,860 bicycle riders in the area, in which the percentage of helmeted riders rose
      from 5% in 1987 to 62% in 1993 (p < 0.001). For MCCs, severe HIs declined from
      20% before passage of the helmet law to 9% afterward (p < 0.001). Mortality
      decreased for BCs and MCCs (p < 0.05), and length of hospital stay and ICU stay
      decreased for BCs (p < 0.05). The percentage of helmeted BC admissions rose from
      0% to 32% (p = 0.009), and helmeted MCC admissions rose from 41% to 80% (p <
      0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7636904
TI  - Gastric mucosal pH and oxygen delivery and oxygen consumption indices in the
      assessment of adequacy of resuscitation after trauma: a prospective, randomized
      study.
AB  - OBJECTIVE: To compare gastric mucosal pH (pHi) and global oxygen variables
      [Oxygen Delivery Index (DO2I) and Oxygen Consumption Index (VO2I)] as indicators
      of adequacy of resuscitation after major trauma. METHODS: Twenty-seven patients
      were prospectively randomized into two groups: group 1 (n = 11), normalization
      and maintenance of pHi at or above 7.30; and group 2 (n = 16), maintaining a DO2I
      of 600 and a VO2I of > 150. The groups had statistically similar injury severity
      scores, lactate, and base deficit. RESULTS: The goals of therapy were achieved
      within 24 hours of admission in 10 of the 11 patients in group 1 and in 15 of the
      16 patients in group 2. One patient (9.1%) in group 1 died. This patient had
      transient stabilization of pHi to 7.3 and subsequently had persistent mucosal
      acidosis. Of the 10 patients with pHi > 7.3 at 24 hours, 9 survived. In group 2,
      5 (31.3%) died. Four of the 5 nonsurvivors had achieved DO2I and VO2I goals, but
      had pHi < 7.3 at 24 hours. A comparison of time taken for optimization of DO2I,
      VO2I, lactate, base excess, and pHi showed pHi and lactate as the variables
      different in survivors and nonsurvivors. Six of the 8 patients who developed
      multiple organ dysfunction syndrome had pHi < 7.3 at 24 hours. Persistently low
      pHi was the first sign of bacteremia (3 patients), small bowel gangrene or
      pregangrene (2 patients), intestinal anastomotic leak (2 patients), intra
      abdominal hypertension (4 patients), and intra-abdominal abscess (5 patients). It
      was the first finding in all the nonsurvivors at least 72 hours before death.
      CONCLUSIONS: pHi may be an important marker to assess the adequacy of
      resuscitation. pHi monitoring may provide early warning for systemic
      complications in the postresuscitation period.

PMID- 7636908
TI  - Prognostic factors after acute subdural hematoma.
AB  - Factors that have been shown to affect outcome after acute subdural hematoma
      (ASDH) include age, Injury Severity Score (ISS), intracranial pressure (ICP),
      direct admission to a trauma center, presence of subarachnoid hemorrhage, score
      on the Glasgow Coma Scale (GCS), and timing of operation. However, these data
      come from selected patient populations (e.g., operated, comatose, or minimally
      symptomatic patients, etc.). In an effort to evaluate factors that predict
      outcome for the entire spectrum of ASDH patients, we evaluated 211 patients with
      ASDH and GCS scores of 3 to 15. One hundred twenty-eight patients (61%) were
      managed nonoperatively (Nonop), whereas 83 (39%) were managed with craniotomy
      [operatively (Op)]. Op patients had more severe brain injuries, as evidenced by
      their lower GCS scores (Op 7.8 vs. Nonop 10.7, p = 0.0001), higher incidence of
      large ASDH with midline shift (Op 61% large ASDH, 83% midline shift vs. Nonop 16%
      large ASDH, 30% midline shift, p = 0.001 for each comparison), and higher
      incidence of basilar cistern effacement (Op 61% vs. Nonop 21%, p = 0.001). Thirty
      five percent of the Op patients had their hematoma evacuated within 4 hours
      (early), whereas 65% did not (delayed). Early Op patients had a significantly
      lower incidence of functional survival (early = 24% vs. delayed = 51%, p = 0.02).
      The early patients seem to have had more significant head injuries, as evidenced
      by their lower GCS scores (early = 7.0 vs. delayed = 8.4), higher incidence of
      associated intracranial injuries (early = 1.14 vs. delayed = 0.85), and higher
      incidence of cistern effacement (early = 76% vs. delayed = 53%, p =
      0.002).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7636909
TI  - Effects of parenteral and enteral nutrition on gut-associated lymphoid tissue.
AB  - Changes in mucosal defense have been implicated as important factors affecting
      infections complications in critically ill patients. To study the effects of
      nutrient administration on gut-associated lymphatic tissue (GALT), ICR mice were
      randomized to receive chow plus intravenous saline, intravenous feeding of a
      total parenteral nutrition (TPN) solution, or enteral feeding of the same TPN
      solution. In a second series of experiments, a more complex enteral diet (Nutren)
      was compared with chow feeding and enteral TPN. After 5 days of feeding with
      experimental diets, lymphocytes were harvested from the mesenteric lymph nodes
      (MLNs), Peyer's patches (PPs), lamina propria (LP) cells, and intraepithelial
      (IE) spaces of the small intestine to determine cell yields and phenotypes. Small
      intestinal washings, gallbladder contents, and sera were collected and analyzed
      for immunoglobulin A (IgA) levels. In both series of experiments, there were no
      significant changes within the MLNs. There were significant decreases in total
      cell yields from the PPs, IE spaces, and LP in animals fed with TPN solution,
      either enterally or parenterally, as compared with chow-fed mice. Total T cells
      were decreased in both TPN-fed groups in the PPs and LP, whereas total B cells
      were decreased in the PP, IE, and LP populations. Total cell numbers remained
      normal in the Nutrenfed group, except for a decrease in LP T cells. CD4+ LP cells
      decreased significantly with a reduction in the CD4/CD8 ratio in mice fed TPN
      solution either intravenously or enterally, whereas IgA recovery from small
      intestinal washings was significantly decreased in the same groups.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7636910
TI  - Triiodothyronine (T3) supplementation maintains surfactant biochemical integrity
      during sepsis.
AB  - Surfactant functional effectiveness is dependent on phospholipid compositional
      integrity: sepsis decreases this through an undefined mechanism. Sepsis-induced
      hypothyroidism is commensurate and may be related. This study examines the effect
      of triiodothyronine (T3) supplementation on surfactant function, metabolism, and
      composition during sepsis. Male Sprague-Dawley rats (n = 75) underwent sham
      laparotomy or cecal ligation and puncture (CLP) with or without T3
      supplementation (CLP/T3; 3 ng/hr). Twenty-four hours later, surfactant was
      obtained by lavage. Total phospholipids were determined by chromatography.
      Choline phosphate cytidyltransferase (CT) activity was determined by the
      formation of cytidine diphosphate (CDP)-choline. In vivo lung compliance was
      determined by lung inflation; surfactant hysteresis plots were determined on a
      pulsating bubble surfactometer. Lung compliance and surfactant hysteresis plots
      were significantly affected by sepsis; T3 modulated this (dynamic compliance:
      sham = 0.66 +/- 0.02, CLP = 0.47 +/- 0.06, CLP/T3 = 0.56 +/- 0.02 mm Hg/mL; p <
      0.05). Sepsis produced a decrease in phosphatidylglycerol, and phosphatidic acid,
      with an increase in lesser surface active lipids phosphatidylserine and
      phosphatidylinositol. Hormonal replacement prevented these alterations. Lung CT
      activity was increased by sepsis independent of T3 treatment. Thyroid hormone may
      have an active role in lung functional preservation during sepsis caused by
      maintenance of surfactant biophysical and compositional homeostasis.

PMID- 7636911
TI  - Pulmonary fibroblast function in an acute lung injury model.
AB  - The role of pulmonary fibroblasts (PFBs) in early adult respiratory distress
      syndrome is poorly understood. To investigate PFB cellular function in acute lung
      injury, New Zealand rabbits (2 to 3 kg) were given either three daily doses of
      phorbol myristate acetate (PMA; 65 micrograms/kg, IV), a potent stimulator of
      oxygen radical formation, or saline (control). On day 4, the lungs were
      harvested, subjected to enzymatic digestion, and PFBs isolated via serial
      subculture. Proliferation was assessed via 6-hour pulsed [3H]thymidine
      incorporation and by creating 5-day growth curves. Confluent PFB cultures were
      assessed for collagen production and total protein production, as well as
      interleukin (IL)-1 alpha secretion. Qualitative comparisons using transmission
      electron micrography were also made. There were no differences between PFBs
      harvested from control versus PMA-treated animals in terms of growth rates, total
      protein, and IL-1 alpha production. However, there was a significant difference
      in collagen production, with the PMA-treated animals' PFBs producing 35% more
      collagen than controls. Transmission electron micrography revealed PMA
      fibroblasts to be smaller (two to three times), have more dark staining granules,
      and have hypertrophied smooth endoplasmic reticulum--all consistent with
      increased metabolic activity. This suggests that pulmonary fibrosis, a late
      development in adult respiratory distress syndrome, may be triggered during the
      acute phase of lung injury. The increase in collagen synthesis is not related to
      PFB proliferation or the secretion of IL-1 alpha.

PMID- 7636912
TI  - Maintenance of serum albumin levels in pediatric burn patients: a prospective,
      randomized trial.
AB  - A prospective, randomized trial was performed to determine whether maintaining
      serum albumin levels in burned pediatric patients had any effect on morbidity and
      mortality. Patients < 19 years of age with burns > 20% total body surface area
      were randomized to receive supplemental albumin to maintain levels 2.5 to 3.5
      g/dL ("High Albumin") or were given albumin only if levels dropped < 1.5 g/dL
      ("Low Albumin") after completing burn shock resuscitation. The 36 patients in the
      Low Albumin group were well matched for age, burn size, depth of injury, and
      inhalation injury when compared with the High Albumin group (34 patients). As
      expected, serum albumin levels were significantly lower in the Low Albumin group
      when compared with the High Albumin group. No differences between groups were
      noted for resuscitation needs, maintenance fluid requirements, urine output, tube
      feedings received, days of antibiotic treatment, or ventilatory requirements. No
      differences in hematology, electrolytes, or nutritional laboratories were found.
      Finally, length of stay, complication rate, and mortality were not affected by
      albumin treatment. Albumin supplementation to maintain normal serum levels does
      not seem to be warranted in previously healthy children who suffer severe burns
      and who receive adequate nutrition.

PMID- 7636913
TI  - Xenogeneic mouse fibroblasts persist in human cultured epidermal grafts: a
      possible mechanism of graft loss.
AB  - Recent reports suggest that long-term graft take of cultured epidermal autografts
      (CEAs) is less than 50% when late graft loss is considered. The characteristics
      of late CEA loss suggest that it may occur as a result of an immunologic reaction
      to persistent xenogeneic cells and/or proteins used to grow CEA. In this study we
      examined whether immunologically reactive, mouse 3T3 fibroblasts used as feeder
      layers can persist in primary, secondary, and tertiary human CEA. We cocultured
      keratinocytes from 11 separate burn patients with growth-arrested 3T3
      fibroblasts. After removing visible 3T3 fibroblasts from CEA with trypsinization,
      we allowed CEA to reach confluence. We then harvested CEA either as primary,
      secondary, or tertiary cultures. We detected mouse fibroblasts using fluorescence
      activated cell sorting (FACS) with a monoclonal antibody specific for mouse major
      histocompatibility (MHC) antigens. We detected mouse MHC class II antigens by
      performing Western immunoblotting with another mouse MHC-specific monoclonal
      antibody. By FACS we identified mouse fibroblasts in 100, 75, and 62.5% of
      primary, secondary, and tertiary passage CEAs, respectively. Similarly by
      immunoblotting we found mouse MHC class II antigen in 100, 80, and 66.7% of
      primary, secondary, and tertiary CEAs. These results demonstrate that xenogeneic
      fibroblast feeder layers capable of generating immunogenic transplantation
      antigens persist in CEAs. The persistence of these cells and their antigen
      expression may contribute to CEA loss.

PMID- 7636914
TI  - Beneficial effects of a bradykinin antagonist in a model of gram-negative sepsis.
AB  - Activation of the kallikrein-kinin system in sepsis has long been recognized, but
      its role, beneficial or pathologic, has not been determined. Recently, however,
      specific bradykinin (BK) antagonists have become available and we sought to
      determine the effects of a BK antagonist, NPC17731, in a model of sepsis-induced
      acute lung injury (ALI). METHODS: Anesthetized swine were studied for 5 hours,
      receiving a 1-hour infusion of saline (Controls) or live Pseudomonas aeruginosa
      (Septic untreated). Treatment groups received a 5 mg/kg bolus of NPC17731
      followed by a 1 mg/kg bolus hourly commencing either just before sepsis
      (Pretreatment) or 30 minutes following the onset of sepsis (Posttreatment).
      RESULTS: Septic untreated animals showed a rapid, progressive decline in arterial
      PaO2 compared to controls, and this was significantly improved in both treatment
      groups. Bronchoalveolar lavage at 5 hours in both treatment groups also showed
      significant decreases in neutrophil (PMN) counts and protein content compared to
      untreated septic animals, indicating decreased PMN migration and alveolar
      capillary membrane damage. Both treatment groups also showed reduced PMN
      sequestration in the lung compared to untreated animals, although PMNs did
      exhibit significant upregulation of PMN CD18 receptor expression and superoxide
      generation. CONCLUSIONS: These data imply a significant role for BK in the
      pathogenesis of sepsis-induced ALI. Use of a competitive BK antagonist
      significantly attenuated the development of ALI without inhibiting PMN
      activation. BK antagonists may be a useful adjunct in the armamentarium against
      sepsis-induced ALI.

PMID- 7636915
TI  - Nitric oxide mediates redistribution of intrarenal blood flow during bacteremia.
AB  - The normal or hyperdynamic circulatory response during the early phases of the
      systemic septic response is associated with renal microvascular constriction and
      can result in renal dysfunction. Intrarenal redistribution of blood flow from the
      outer cortex to the medulla appears to account for decreased glomerular
      filtration in spite of normal or elevated renal blood flow, but the mechanisms of
      this response are not well described. Nitric oxide is recognized as an important
      regulator of regional blood flow during both normal and pathologic conditions
      including sepsis, and we hypothesized that alterations in nitric oxide contribute
      to redistribution of renal blood flow during sepsis. The current study used laser
      Doppler fluximetry and clearance of p-aminohippuric acid (effective renal plasma
      flow, ERPF) to study intrarenal distribution of blood flow during basal
      conditions and during normodynamic Escherichia coli bacteremia, with and without
      inhibition of nitric oxide. Inhibition of nitric oxide in normal animals resulted
      in a decrease in ERPF (-19%) with a decrease in cortical flux (-39%) without
      alteration of medullary flux. Bacteremia resulted in a decrease in cortical flow
      (-17%), an increase in medullary flow (36%), and a modest reduction (-9%) in
      ERPF. Inhibition of nitric oxide synthase during bacteremia worsened cortical
      flow (-43%), reversed the increase in medullary flux (-42%), and further impaired
      ERPF (-28%). These data suggest that nitric oxide regulates renovascular tone
      during normal conditions and bacteremia, and indicate that it is a prime mediator
      of intrarenal redistribution of blood flow during sepsis.

PMID- 7636916
TI  - Interleukin-8 increases endothelial permeability independent of neutrophils.
AB  - Interleukin-8 (IL-8) has been associated with a variety of hyperinflammatory
      states and adverse clinical events. Circulating IL-8 levels correlate with the
      severity of tissue trauma, and excessive elevations of IL-8 are associated with
      postinjury adult respiratory distress syndrome and multiple organ failure. While
      IL-8 is a potent neutrophil (PMN) chemoattractant and activator and enhances PMN
      transendothelial migration, it also acts to inhibit PMN adhesion to stimulated
      endothelial cells (ECs). We hypothesized that IL-8 could interact directly with
      ECs to increase permeability independent of PMNs. Human umbilical vein ECs
      (HUVECs) were cultured on collagen-coated micropore filters, and integrity of the
      EC monolayer measured by albumin flux across the filter. Cytochalasin D was used
      as a positive control. IL-8 induced increased permeability at a concentration of
      1000 ng/mL. This effect was abrogated by preincubation of HUVECs with a protein
      synthesis inhibitor (cycloheximide). These data suggest a role for IL-8 in
      promoting endothelial leak independent of PMNs, via a mechanism involving protein
      synthesis.

PMID- 7636917
TI  - Analysis of hospital records in four African countries, 1975-1990, with emphasis
      on infectious diseases.
AB  - Detailed standardized annual reports are analysed for 17 rural hospitals in four
      African countries, with admission figures of 1.2 million patients (excluding
      deliveries) and more than 67,000 deaths over a period of 16 years. The countries
      involved are Zambia, Tanzania, Kenya and Ghana. Figures on admission, causes of
      death and clinical case fatality rates are presented per country and per 4-year
      calendar period for the most important infectious diseases. The number of
      admissions increased substantially in 3 of the 4 countries (50-77%) between 1976
      and 1990, but admission rates (per 1,000 population per year) by much less (6
      25%), indicating that a large part of the increase in the volume of services was
      due to population growth. The number of infectious disease admissions in Ghana,
      however, decreased by 12% and even more in terms of admission rates (by 42%).
      About 75% of all admissions in children below 15 years of age were due to
      infections and infection related diseases; for adults this figure was 31%.
      Malaria is the single most important infectious disease both in terms of
      admissions and as a cause of death; it has increased substantially in three of
      the four countries. Bacterial infections, in particular pneumonia,
      gastroenteritis, meningitis and tuberculosis, are also important diseases in
      terms of admissions and deaths. On the whole they have remained at more or less
      the same level in 1975-1990 in terms of both admissions and deaths. Immunizable
      diseases and measles, once important as causes of admissions and deaths, have
      declined in all countries. Case fatality rates vary substantially by type of
      disease. They are very high for tetanus (36.7-68.8%) and meningitis (14.7-43%),
      and low for malaria (0.6-4.6%). However, they vary considerably in the four
      countries included in the study and are usually lower in children than in adults.
      A need for detailed studies with good "standardized" hospital records is
      emphasized. Representative data are needed from all hospitals in a given
      catchment area, with defined diagnoses for diseases and details regarding age and
      sex. This kind of information is highly desirable for planning and operation of
      curative and preventive medical care in developing countries.

PMID- 7636919
TI  - Analysis and diagnostic use of Brugia malayi adult antigen in bancroftian
      filariasis.
AB  - Detergent-soluble antigens of Brugia malayi adult worms (BmA SDS S Ag) were
      analysed for their antigenic activity and potential use in diagnosis of
      bancroftian filariasis. Analysis of SDS-PAGE fractions of BmA SDS S Ag against
      antifilarial antibodies, that is, human filarial serum immunoglobulin G and anti
      BmA SDS S Ag antibody, revealed two active antigen fractions: BmA-6 and BmA-9.
      Antibodies raised to BmA-6 and BmA-9 were tested with antigens isolated from
      infected human body fluids such as circulating filarial antigen (CFA2), urinary
      filarial antigen (UFAC2) and hydrocele fluid antigen (HFA). Both antibodies
      showed high reactivity with CFA2-1, 6 and 9 as well as UFAC2-5, 6 and 9 antigenic
      fractions. In immunoblotting studies, anti BmA-6 antibody detected specific
      antigens of high microfilaraemic reactivity such as 120, 54, 26 and 22 kDa. In
      inhibition ELISA using anti BmA SDS S Ag antibody and antigen fraction BmA-6,
      filarial antigen was detected in 85% of microfilaraemic, 35% of clinical filarial
      and 20% of endemic normal sera samples. When anti BmA SDS S Ag antibody and BmA-9
      were used, 80% of microfilaraemic, 35% of clinical filarial and 25% of endemic
      normal sera showed positive reaction for filarial antigen. The analysis of urine
      samples showed the presence of filarial antigen in 76 and 72% of microfilaraemic
      cases using BmA-6 and BmA-9 fractions respectively while only 20% of endemic
      normals were positive using both the antigen fractions.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7636918
TI  - Frequency of defaecation and stool consistency in Nigerian students.
AB  - To provide a context in which to interpret reports of bowel dysfunction, it is
      important to know bowel patterns of the general population. We asked 600
      apparently healthy students at the Medical School of the University of Ibadan,
      Nigeria, to complete a questionnaire. Their diet consists mainly of foods derived
      from tubers and legumes such as yam, cassava and beans. The majority of our
      students defaecated between three times per day and three times per week.
      Subjects with one bowel movement per day were in the minority. There were no
      marked differences in bowel frequencies between sexes or nationalities. Most
      defaecations occurred in the early morning, in women earlier than in men. There
      was no relation between bowel frequency and stool consistency. Approximately 20%
      of subjects took laxatives regularly. More often than not, laxatives were taken
      for reasons unrelated to bowel habit, indicating the need for a health education
      programme to warn against self-medication and indiscriminate use of laxatives in
      the population. Our results are compared to reported findings in surveys of other
      populations.

PMID- 7636921
TI  - A randomized trial of the impact of rope-pumps on water quality.
AB  - Rope-pumps are now widely promoted as a low cost, easily maintained means to
      improve water availability in developing countries. However, in some instances
      their acceptance has been limited by concerns over the microbiological quality of
      the water. This study looked at the well water quality under a variety of
      conditions, comparing unimproved bucket and rope wells with wells with a windlass
      and rope-pump wells with and without a concrete cover. Other factors influencing
      the water quality were also examined. Results indicate a 62% reduction of the
      geometric mean of the faecal coliform contamination of the well water as a result
      of the installation of a rope-pump with or without a concrete cover. Other
      factors found to influence the level of contamination of water in hand-dug wells
      were rainfall, number of households using the well, amount of water extracted
      daily and the distance of the well from the nearest kitchen. The last three
      factors probably reflect domestic activities with poor hygiene around the well.
      The installation of a simple rope-pump on family wells improves the water quality
      and availability at a favourable cost/benefit ratio.

PMID- 7636920
TI  - Case management by community health workers of children with acute respiratory
      infections: implications for national ARI control programme.
AB  - Health worker performance in the management of children with acute respiratory
      infections (ARI) was assessed in two local government areas (LGAs) in Nigeria.
      The data derived were utilized to identify training needs. Survey instruments
      included an inventory list for ARI-related equipment and supplies, observation
      checklists for children presenting to the health worker with ARI symptoms, a
      questionnaire for exist interviews with mothers, and a supervisor performance
      checklist. One hundred and twenty-three health workers in Ife Central LGA and 50
      in Ojo were observed at selected public health facilities. Most health workers
      took a good general history, but specific ARI-related history and physical
      examination were frequently omitted. Symptomatic diagnosis and treatment were
      common. Drugs most commonly prescribed for treatment of ARI were chloroquine,
      paracetamol and antibiotics. Essential drugs and supplies for ARI management were
      not available in some facilities. Communication with mothers was generally
      unsatisfactory and instruction on home management incomplete. Many of the health
      workers had not attended a continuing education programme in the previous two
      years and supervision which could have provided on-the-spot training was
      irregular. Improvements in ARI case management will require attention to policy,
      logistics, training (including in-service education) and supervision. The
      possible role of an integrated approach to the management of the sick child in
      improving the quality of health worker performance is discussed.

PMID- 7636922
TI  - APACHE II scoring for predicting outcome in cerebral malaria.
AB  - The APACHE II (Acute Physiology and Chronic Health Evaluation) severity-of
      disease classification system was used to stratify the prognosis of 72 adult
      patients with cerebral malaria. Overall mortality was 13.89%. With the cut-off
      point at a score of 24, the APACHE II score stratified the patients' mortality
      outcome with 95.8% accuracy. High APACHE II score, deep unconsciousness, acute
      renal failure and acidaemia were identified as poor prognostic factors. We
      suggest that the APACHE II system is useful for stratifying the prognosis of
      group outcome in cerebral malaria patients.

PMID- 7636923
TI  - The effect of stay in a maternity waiting home on perinatal mortality in rural
      Zimbabwe.
AB  - A hospital-based cohort study was carried out in a district hospital in Zimbabwe
      to evaluate the effect of a maternity waiting home on perinatal mortality.
      Information on antenatal risk factors, use of antenatal care, access to the
      hospital and stage of labour on arrival was collected for each woman delivering
      at the hospital during the period 1989-1991 (n = 6438). Women who stayed in the
      maternity waiting home had a lower risk of perinatal death compared to women who
      came directly from home to the hospital during labour. The crude relative risk of
      perinatal death for the women coming from home was 1.7 (95% confidence interval
      (CI) 1.1-2.6; P < 0.05). After adjusting for the effect of potential confounding
      variables, the relative risk decreased to 1.5 (95% CI 0.95-2.5, P = 0.07).
      However, when the analysis was restricted to women with antenatal risk factors
      there was a significant 50% reduction in the risk of perinatal death for the
      women who stayed at the maternity waiting home compared to women who came from
      home during labour (adjusted relative risk 1.9; 95% CI 1.1-3.4; P < 0.05). The
      use of maternity waiting homes has the potential to reduce perinatal mortality in
      rural areas with low geographic access to hospitals and merits further
      evaluation.

PMID- 7636925
TI  - Eosinophilic myositis resulting from sarcocystosis.
AB  - Muscle sarcocystosis is a parasitic infection acquired by ingestion of sporocysts
      of Sarcocystis species. A case is described where symptoms of fever, chronic
      myositis and eosinophilia were present. Diagnosis was made via muscle biopsy.
      Improvement and cure coincided with treatment with cotrimoxazole. A limited
      review of human muscle sarcocystosis and an outline of the gaps in the knowledge
      of this infection is presented.

PMID- 7636924
TI  - Behaviour of specific IgM, IgG and IgA class antibodies in human leptospirosis
      during the acute phase of the disease and during convalescence.
AB  - The behaviour of specific IgM, IgG and IgA class antibodies in human
      leptospirosis was studied by ELISA. Two groups of patients were followed up, 57
      of them in the acute phase and 10 during convalescence, the latter with a mean
      follow-up of 10.5 months. IgM class antibodies were detected starting on the 2nd
      day of symptoms and were observed in 100% of patients up to the 5th month, in
      66.7% up to the 7th month and in 50% up to the 12th month after the onset of
      symptoms. IgG class antibodies were first detected on the 7th day of symptoms in
      9.1% of patients, with maximum reactivity (87.5%) between the 2nd and 3rd month,
      and were not detected at all in one patient. IgA class antibodies were detected
      starting on the 5th day of symptoms in 7.7% of patients, and in all patients on
      the 15th day, persisting in 100% of cases up to the 9th follow-up month. During
      the 12th month, they were observed in 83.3% of patients. The results indicate
      that an anti IgA ELISA could be of great value in seroprevalence studies on human
      leptospirosis.

PMID- 7636926
TI  - Infectiousness of HBsAg carriers in Malaysia.
AB  - HBV-DNA were analysed in 330 HBsAg-positive carriers in Malaysia by dot-blot
      hybridization and polymerase chain reaction. Seventy-three (22.12%) were positive
      for the virus. Of these, 65 (89%) were males and 8 (11%) were females.
      Statistically, there was no significant difference (P = 0.13). No significant
      decline in HBV-DNA with age in the Malay and Chinese males was observed (P =
      0.2). Prevalence of HBV-DNA was higher in the Chinese carriers than in the Malay
      carriers for most age groups in both sexes. Sixty-one HBV-DNA-positive carriers
      were also positive for HBeAg. However, three individuals were positive only for
      anti-HBe, one was positive for both HBeAg and anti-HBe, and eight were negative
      for both HBeAg and anti-HBe. Fifty-seven were positive for HBeAg but negative for
      HBV-DNA. No relation was observed between raised alanine aminotransaminase and
      aspartate aminotransaminase levels and the presence of HBV-DNA (P = 0.4).

PMID- 7636927
TI  - Pattern of adult malignancies in Zambia (1980-1989) in light of the human
      immunodeficiency virus type 1 epidemic.
AB  - This study analysed histopathological and haematology records of 7836 neoplasms
      seen during the period 1980-1989 at the University Teaching Hospital, Lusaka,
      Zambia. The crude incidence rate of each malignancy per 100,000 adults per year
      was calculated and the patterns of malignancies were compared for the periods
      1980-1983 and 1984-1989, the later coinciding with the advent of the human
      immunodeficiency virus (HIV) epidemic. The six most common tumours were carcinoma
      of the cervix (19.6%), Kaposi's sarcoma (7%), bladder carcinoma (6.3%), hepatoma
      (5.8%), lymphoma (4.6%) and carcinoma of the breast (4.4%). Significant increases
      in the crude incidence rates of Kaposi's sarcoma (KS) and carcinoma of the breast
      were observed during the last 6 years of the study period (P = 0.001). Nodal KS
      showed the most significant rise from a crude incidence rate of 0.25 per 100,000
      adults per year in the 1980-1983 period to 1.11 during the 1984-1989 period. In
      contrast to findings from Europe and the USA, no significant increase in non
      Hodgkin's lymphoma was detected in Zambia following the HIV epidemic.

PMID- 7636928
TI  - Lymphoma as a cause of false positive serology for visceral leishmaniasis (kala
      azar) using the indirect haemagglutination (IHA) method.

PMID- 7636929
TI  - Bacterial resistance to antibiotics.

PMID- 7636930
TI  - Prevention and early detection of leprosy in children.
AB  - India with its 4 million cases of leprosy, accounts for one-third of the world's
      population of leprosy patients. One-fourth of them are below 15 years of age. We
      report a 5-year follow-up study of healthy children who were close contacts of
      leprosy patients, in order to: 1. detect subclinical infection and observe the
      development of overt disease by using the Fluorescent Leprosy Antibody Absorption
      Technique (FLA-ABS) and the lepromin test which assess the humoral and cell
      mediated immunity (CMI), respectively; 2. evaluate the efficacy of dapsone as a
      chemoprophylactic agent in the 'at risk' contacts. Four-hundred-and-fifty-five
      healthy contacts were studied. Majority of the contacts of multibacillary
      patients (303) were FLA-ABS positive (75 percent) and lepromin negative (55
      percent) showing that although most of them had been infected, the lepromin
      status was negative (P < 0.01). On the other hand, the majority of the contacts
      of paucibacillary patients (152) were lepromin positive (57 percent) (P < 0.05).
      Furthermore, only 61 percent of contacts of paucibacillary patients were FLA-ABS
      positive as compared to 75 percent of contacts of multibacillary patients
      demonstrating that the former had been exposed to a lesser quantum of infection
      (P < 0.05). On the basis of results of FLA-ABS and lepromin tests, these 455
      contacts were classified into four groups, viz. Group I comprising children who
      were FLA-ABS positive and lepromin positive; Group II, who were FLA-ABS positive
      and lepromin negative; Group III, who were FLA-ABS negative and lepromin
      positive; and Group IV who were FLA-ABS negative and lepromin negative.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7636931
TI  - Epidemiology of cholera in Delhi--1992.
AB  - Cholera is endemic in Delhi and is a highly seasonal disease. Suspected cholera
      cases are referred to Infectious Diseases Hospital, Delhi. Rectal swabs from 2783
      cases were bacteriologically examined during 1992, out of which 1075 were found
      to be positive for Vibrio cholerae O1 biotype El Tor. First isolation was made on
      3 April and the last on 14 December. About 87 per cent isolations were made
      between May and September, which are summer and monsoon months in Delhi. Detailed
      epidemiological information was collected for about 198 cases of diarrhoea out of
      which 103 were confirmed cases of cholera. Half of these cases occurred in
      children below 10 years of age. The other major group affected was adult females,
      especially housewives. All the cholera cases occurred in those who were
      illiterate or educated up to primary level. Important risk factors were: contact
      with person having similar illness, storage of water in wide-mouthed containers,
      use of glass or mug to draw water from containers, absence of sanitary latrines
      and habit of washing hands with water alone after defecation, before cooking and
      eating food. About 30 percent cases had access to piped water supply which was
      found safe in Delhi during 1992. The findings suggest that the hygienic practices
      were more important than contaminated water sources for transmission of cholera
      in Delhi during the year 1992.

PMID- 7636932
TI  - The haematological manifestations of visceral leishmaniasis in infancy and
      childhood.
AB  - The haematological manifestations were reviewed in 94 patients (55 males and 39
      females) with visceral leishmaniasis. Their ages ranged from 4 months to 12 years
      (mean per cent 1.8 years). All patients had splenomegaly and were anaemic, while
      (73 per cent) were neutropenic and (56 per cent) thrombocytopenic. Coagulation
      abnormalities were encountered in 10 (11 per cent) patients; in four patients
      this was associated with disseminated intravascular coagulopathy. Bone marrow was
      hypercellular in (90 per cent), normocellular in (5 per cent), and hypocelluar in
      (4 per cent). Also variable degrees of erythrophagocytosis and leukophagocytosis
      were noted with preponderance of histiocytes (46 per cent) and granulomatous
      formation (25 per cent). Low haemosiderin content in the bone marrow was noted,
      which together with the finding of high serum ferritin is consistent with anaemia
      of chronic inflammation. Hypersplenism, haemophagocytosis and granulomatous
      lesions of the bone marrow, chronic inflammation, and dietary factors appear to
      be the most important factors in the causation of the haematological changes in
      visceral leishmaniasis.

PMID- 7636933
TI  - Intestinal parasites in HIV-seropositive Zambian children with diarrhoea.
AB  - We undertook a study over a period of 9 months to define the frequency of
      parasitic infections in hospitalized children with diarrhoea between the ages of
      15 months and 5 years. Every alternate day, mothers of all children admitted with
      diarrhoea between 09.00 hours and 12.00 hours to one of the wards of the
      Department of Pediatrics and Child Health of the University Teaching Hospital
      (UTH) in Lusaka, Zambia, were interviewed for enrollment of their children into
      the study. A total of 178 children with diarrhoea were enrolled in the study. Of
      these 44 (25 per cent) were HIV seropositive and 134 (75 per cent) were
      seronegative for HIV. Out of 44 HIV-seropositive patients, 20 (45 per cent) had
      acute diarrhoea and 24 (55 per cent) had chronic diarrhoea. Of the 134 HIV
      seronegative patients, 68 had acute diarrhoea (51 per cent) and 66 (49 per cent)
      had chronic diarrhoea. At least one intestinal parasite was found in 34 out of
      the 178 children enrolled. The commonest parasites identified were Ascaris and
      Cryptosporidia. No associations were identified between parasite isolation and
      the following: age, sex, or socio-economic status. Cryptosporidium spp. was
      isolated from 6 out of 44 (14 per cent) HIV-seropositive children, while 8 out of
      134 (6 per cent) seronegative children had the parasite (P = 0.01). HIV
      seropositive children with chronic diarrhoea had significantly higher
      cryptosporidium identification rates than those HIV-seropositive children with
      acute diarrhoea [5 out of 24 (21 per cent) patients with chronic diarrhoea
      compared to 1 out of 20 (5 per cent) patients with acute diarrhoea; (P > or =
      0.01)].(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7636935
TI  - Baby check in India: assessing the severity of illness in babies in a Calcutta
      out-patient clinic.
AB  - The objective was to assess whether Baby Check could be used in a different
      cultural setting to where it was developed. Babies were scored using Baby Check
      and then assessed by a physician who had no knowledge of the score. Out-patient
      clinics were held at the Child In Need Institute, Calcutta, India. The subjects
      were 100 babies aged between 0 and 12 months. Ninety-five babies were
      successfully scored and independently graded by a doctor. The total scores ranged
      0 to 53 with a median of 11. Physicians graded two babies as seriously ill that
      required urgent admission; eight required admission for observation and/or
      treatment; 51 were thought to require careful observation and treatment at home;
      and 34 were considered to be mildly ill or well. There were several difficulties
      using Baby Check in Calcutta. Baby Check is designed to assess the severity of
      acute systemic illness in babies. Many babies seen had chronic conditions such as
      malnutrition, as well as an acute illness. There were difficulties translating
      some of the checks. In the study design there is no 'gold standard' against which
      to test physicians' grading of illness or the Baby Check score. Despite these
      problems Baby Check detected the majority of ill babies in the study: with a
      total score cut-off of 12-13 Baby Check had a positive predictive value of 86 per
      cent for detecting babies that required medical attention. Of the babies scoring
      less than 8, 97 per cent did not need admission to hospital.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7636934
TI  - Antibody titre and avidity in saliva and serum are not impaired in mildly to
      moderately undernourished children.
AB  - Avidities and titres of serum IgA, IgM, IgG, and salivary IgA antibodies for
      poliovirus type 3, beta-lactoglobulin and E. coli O antigens were analysed in
      well-nourished (n=58) and mildly to moderately undernourished (n = 18) 1-7-year
      old children, living in slums in Sao Paulo, Brazil, with irregular water supply
      and no sewage system. The serum titres of antibodies in the undernourished
      children were not statistically different from the well-nourished ones, except
      for the IgA anti-beta-lactoglobulin titres which were lower in the youngest
      undernourished group. In respect to avidity of the serum antibodies, no
      statistical difference was observed, except that the youngest undernourished
      children presented avidities of serum IgA anti-E. coli O antigens higher than
      those of the well-nourished children of the same age range. With respect to
      salivary titres and avidities no difference was observed between well-nourished
      and undernourished children. The fact that the undernourished children were not
      deficient in antibody amount or quality, as measured in this study, suggests that
      in this respect their immune system was not impaired.

PMID- 7636937
TI  - A unified pattern standard score method for construction of age-related weight
      for-height.
AB  - Analysis of data from the Shiraz (Iran) growth study requires to take age into
      account when assessing weight-for-height of school children aged 6-12. A unified
      structure standard score method for construction of weight-for-height is designed
      to overcome the age dependence problem. This method first applies Healy-Rasbash
      Yang (HRY) distribution-free estimation method of age-related centiles to
      calculate log (weight) and height-for-age centiles, and convert them to their
      standard scores. These scores are age and sex independent, and are called weight
      index (WI) and height index (HI), respectively. Then WI is regressed on HI and
      age-adjusted centiles of weight-for-height are derived at each age of weight and
      height to their respective zeta-scores. Finally, weight-for-height centiles are
      drawn for each age-sex category of children. This zeta-score method is shown to
      be efficient, simple, and stable, and may generally be applied to other data.

PMID- 7636936
TI  - Effectiveness of adjunctive treatment with steroids in reducing short-term
      mortality in a high-risk population of children with bacterial meningitis.
AB  - Bacterial meningitis is still an important cause of death and/or persistent
      nervous system damage in children living in developing countries. The aim of the
      study was to evaluate the effectiveness of steroids in reducing mortality and
      neurologic sequelae in children affected by bacterial meningitis within the
      context of a developing country (Mozambique), where the case-fatality rate of
      this disease is over 30 per cent. Seventy children with bacterial meningitis were
      randomized to receive either conventional antibiotic therapy or antibiotic
      therapy plus dexamethasone. On hospital admission there were no statistically
      significant differences between the two groups with regard to clinical and
      laboratoristic features. When dexamethasone was used early mortality, within 24
      h, was significantly reduced (1/34 v. 8/36, P < 0.05). Total mortality among
      steroid treated patients, including those who were comatose on admission, was
      also reduced even if the difference did not reach statistical significance. A
      favourable trend in terms of fewer serious neurologic abnormalities was also
      observed among survivors in the steroid treated patients (5/26 v. 7/24). Fever
      and CSF abnormalities also disappeared more rapidly in patients receiving
      dexamethasone (P < 0.05). This study showed that the beneficial effect of
      adjunctive steroid therapy in children with bacterial meningitis can be even more
      important in areas where the case-fatality rate of this disease is still very
      high.

PMID- 7636938
TI  - Study of hepatic functions and prevalence of hepatitis-B surface antigenaemia in
      Omani children with sickle cell disease.
AB  - The prevalence of persistent hepatitis-B surface (HBS) antigenaemia and hepatic
      functions have been determined in 125 children with sickle cell disease (SCD) as
      well as in 100 age-matched healthy children. Hepatic functions and the presence
      of HBS antigenaemia have been followed for 1 year in six children with SCD and 10
      normal children following acute hepatitis-B infection. The prevalence of chronic
      HBS antigenaemia (3 per cent) in children with SCD is not higher than in normal
      children (11 per cent). The significant elevation of serum alanine transferase
      (ALT) and bilirubin concentrations in sickle cell children denotes a process of
      mild hepatocellular dysfunction which is unrelated to hepatitis-B viral
      antigenaemia. The high incidence of chronic HBS antigenaemia accompanied by
      elevated serum ALT and bilirubin concentrations in sickle cell children following
      acute hepatitis-B infection, in addition to the significant impairment of hepatic
      functions in sicklers with chronic HBS antigenaemia compared to those without the
      antigenaemia, point out to the high risk of continual parenchymal hepatic damage
      in these children following acute hepatitis-B infection. Vaccination against
      hepatitis-B virus should eliminate this risk.

PMID- 7636939
TI  - Neonatal sepsis in Dubai, United Arab Emirates.
AB  - The case records of all neonates admitted to the neonatal unit of Al Wasl
      Hospital (Dubai) in a period of 60 months (May 1987-April 1992) were analysed.
      One-hundred-and-six neonates had confirmed sepsis. The most common causative
      organisms were Group B Streptococci (23 per cent), E. coli (17 per cent), Staph.
      epidermidis (17 per cent), and Klebsiella pneumoniae (16 per cent). Group B
      Streptococcus presented as the most common organism in very early (< or = 24
      hours) and early onset (2-6 days) of sepsis (34 per cent, 21/61), Klebsiella
      pneumoniae (24 per cent), Staphylococcal epidermidis (18 per cent) and Candida
      (13 per cent) were most common organisms causing late onset of sepsis (7-30
      days). Pseudomonas aeruginosa and Klebsiella pneumoniae had highest mortality (71
      per cent, 5/7; and 59 per cent, 10/17, respectively). Lowest mortality (4 per
      cent, 1/25) was observed in Group B Streptococcus sepsis. Prematurity, low birth
      weight, and nosocomial sepsis were high risk factors associated with fatal
      outcome.

PMID- 7636940
TI  - Age-related weight-for-height charts for south Iranian school children.
AB  - Analysis of data from the Shiraz (Iran) growth study requires to take age into
      account when assessing weight-for-height of school children aged 6-12. A unified
      structure standard score method is used to construct age-related weight-for
      height. Weight-for-height charts were drawn for each age-sex category of
      children. These charts suggest that local weight-for-height standards should be
      used in clinical work.

PMID- 7636941
TI  - Empyema thoracis in hospitalized children in Kelantan, Malaysia.
AB  - In this study, 31 cases of childhood empyema thoracis admitted over 4 1/2 years
      to the Hospital Universiti Sains Malaysia, in Kelantan, Malaysia, were
      retrospectively reviewed. Twenty-two males and nine females were included, with a
      mean age of 1.9 years (range: 26 days to 7 years). Frequent symptoms were fever,
      cough, and dyspnoea, while common signs were temperature above 38 degrees C,
      decreased breath sounds, dullness to chest percussion, and intercostal recession.
      Radiography demonstrated unilateral moderate to large effusions in 68 per cent of
      cases, while consolidated lung was seen in 45 per cent of patients. Pleural fluid
      cultures were positive for Staphylococcus aureus (48 per cent), Streptococcus
      pneumoniae (7 per cent), while no growth was seen in 42 per cent of cases. Ninety
      four per cent of children had a blood leukocytosis above 10 000 cell/mm3, but
      blood cultures were negative in 21 out of 26 patients (81 per cent). Most cases
      were treated with a combination of intravenous antibiotics and chest tube
      drainage. Antibiotics and pleural tap(s) were used in the remainder. Patients
      stayed in hospital for an average of 20.7 days (range: 4-52 days). Surgical
      intervention was necessary in only four children. The mortality rate at the time
      of discharge was zero, with 100 per cent radiographic resolution among the 23
      patients who were followed-up.

PMID- 7636942
TI  - Organophosphate-induced delayed polyneuropathy.

PMID- 7636943
TI  - Assessment of home management of fever among children in the Ashanti Region of
      Ghana.

PMID- 7636944
TI  - Childhood bacterial meningitis in Barbados: focus on Haemophilus influenzae.

PMID- 7636945
TI  - Epidemiology of human visceral leishmaniasis in Tunisia.

PMID- 7636946
TI  - The impact of intraoperative ultrasonography on surgery for liver neoplasms.
AB  - To analyze the effect of IOUS on surgical decision making, we performed a
      retrospective study of 45 patients who had exploratory laparotomy and IOUS for
      liver neoplasms. Preoperative lesion detection was compared with intraoperative
      findings. The effect of IOUS on the choice of surgical procedure was analyzed.
      Preoperative imaging detected 67% of lesions, 78% when combined with surgical
      inspection and palpation, and 97% were recognized by IOUS. Surgery was modified
      in 23 of 45 cases (51%); 19 of those 23 cases (83%) were based on IOUS findings
      alone. IOUS demonstrated superior lesion detection over noninvasive preoperative
      liver imaging, and IOUS significantly affected surgical decision making.

PMID- 7636947
TI  - Sonographic measurements of the umbilical cord and vessels during normal
      pregnancies.
AB  - Sonographic measurements of the umbilical cord and vessels were performed in 368
      uncomplicated pregnancies, and nomograms of their growth were constructed. All
      measurements were obtained in appropriate for gestational age fetuses in
      pregnancies with accurate dating. From the above measurements, an estimate of
      Wharton's jelly quantity (expressed as square millimeters) was calculated. The
      nomograms presented add another biometric measurement of normally growing fetuses
      and may serve to differentiate between them and those who are found to have
      umbilical cord abnormalities.

PMID- 7636949
TI  - New method for tracking fetal breathing movements using real-time pulsed Doppler
      ultrasonographic displacement measurement.
AB  - To develop a clinical device for monitoring FBM with a simplified mechanism, the
      multichannel pulsed Doppler device was achieved by modifying the ultrasonographic
      module and probe of a cardiotocograph. A new algorithm of signal processing with
      a high-accuracy displacement estimation technique produced real-time and
      continuous displacement calculations. In vivo measurements demonstrated that real
      time output produced commendable quality in FBM tracking. The displacement of a
      few hundred micrometers because of FBM was measured successfully. The results
      suggest that quantitative assessments of FBM should be possible with this
      technique.

PMID- 7636948
TI  - Duplex ultrasonographic assessment of gut blood flow velocity: effect of meal
      composition in normal full-term newborns after first feed.
AB  - We used transcutaneous duplex Doppler ultrasound to measure superior mesenteric
      artery and celiac artery blood flow velocity in 45 normal healthy newborn
      infants. Doppler indices of PSV, TAMV, EDV, and PI were measured immediately
      before and after feeding at 15 minute intervals up to 75 minutes. Maximal changes
      were compared with preprandial baseline values. There were no significant
      differences between the preprandial and postprandial blood pressures and heart
      rates. In the superior mesenteric artery the PSV, TAMV, and EDV rose
      progressively and peaked 30 minutes after feeding in both the milk-fed group and
      the 5% glucose, water-fed group over baseline (73 versus 41% and 110 versus 63%,
      130 versus 100%) (P < 0.05). The PI decreased significantly in the milk-fed group
      only. There were no significant changes in any blood flow velocity parameters
      derived from the celiac artery. We conclude that duplex ultrasonography provides
      a noninvasive means of studying the reactivity of the splanchnic arterial
      circulation to different stimuli. The chemical composition of the meal is a
      significant factor determining postprandial mesenteric hyperemia.

PMID- 7636950
TI  - Endovaginal ultrasonographic measurement of early embryonic size as a means of
      assessing gestational age.
AB  - Crown-rump length has consistently been found to be the most accurate method of
      determining gestational age in the first trimester. The original regression curve
      established by Robinson in 1973 with static arm scanners remains the one most
      widely employed. New endovaginal ultrasonographic probes afford a degree of
      detail that allows embryonic structures to be seen as soon as they are distinct
      from the yolk sac. Previously, measurements of very early embryonic structures
      have mistakenly been labeled crown-rump lengths. There has been widespread use of
      nomograms constructed from regression curves, where the bulk of the data were
      derived from small fetuses and then such curves extrapolated back to embryos of
      very small size. The purpose of this study was to establish a nomogram for
      gestational age assessment by measuring early embryos prior to the development of
      a "crown" or "rump." This present study consisted of 143 patients. To be included
      they had to have had no history of any prior bleeding, and all were delivered of
      singleton infants within 2 weeks of their estimated delivery date by last
      menstrual period. All had a single early embryonic size measurement between 1 and
      25 mm using high-frequency endovaginal probes. Regression analysis revealed a
      linear equation of Gestational age (days) = early embryonic size (mm) + 42 with a
      correlation coefficient r = 0.87; 95% confidence limit = +/- 3 days. We conclude
      that using high-frequency vaginal ultrasonographic probes and having a better
      understanding of embryonic anatomic stages allow for the construction of a
      nomogram of gestational age derived from measurements of early embryonic size
      prior to development of a crown-rump length.

PMID- 7636951
TI  - Breast sonography: technique to mimic mammographic position.
AB  - Positional changes in the breast between supine sonography and mammography may
      cause difficulties in correlating abnormalities. The problem is easily surmounted
      by performing the breast sonogram with the patient in the upright position. This
      study is a prospective evaluation of 10 patients examined sonographically in the
      supine and upright positions. The nipple to lesion distance was measured and the
      clock position estimated on the upright and supine sonograms. These parameters
      were compared to the original mammograms. In all patients the mammographic clock
      position and the distances from the nipple correlated more closely with the
      upright sonogram. The mammographic clock position was the same on the upright
      sonogram in six of 10 (60%), and the remaining four (40%) varied from one half to
      two clock positions. In supine sonography the clock position was the same in two
      of 10 (20%) patients, and the remaining eight (80%) varied from one to three
      clock positions. Most lesions were between 4.5 and 11 cm from the nipple on the
      mammogram. The distances of the lesions from the nipple ranged from 3 to 10 cm on
      upright sonography and from 0 to 4.5 cm on supine sonography. The difference
      between clock positions and the distances from the nipple on upright versus
      supine sonography were statistically significant. Therefore, upright sonography
      is more accurate in localizing mammographically identified lesions than the
      standard supine sonographic technique.

PMID- 7636952
TI  - Transvaginal sonography, color flow imaging, computed tomographic scanning, and
      CA 125 as a routine follow-up examination in women with pelvic tumor: detection
      of recurrent disease.
AB  - We were trying to determine whether transvaginal sonography combined with color
      flow imaging should be used routinely for detecting recurrent pelvic tumors in
      patients treated for pelvic cancer. Eighteen patients who had completed their
      treatment for pelvic tumor were examined every 6 months by gynecologic
      examination, a CT scan, serum CA 125 levels, and transvaginal sonography with
      color flow imaging. Laparotomy or fine-needle biopsy was performed when a
      recurrent pelvic mass was observed or suspected on CT scans or transvaginal
      sonography. In nine of 18 patients a recurrent pelvic tumor was observed or
      suspected on CT scans or on transvaginal sonography. A recurrent pelvic tumor was
      diagnosed on laparotomy in five patients. In four patients, only a fine-needle
      biopsy was performed and only two of them had positive results. The highest
      sensitivity and specificity for detecting recurrent pelvic tumors were achieved
      by transvaginal sonography (100 and 91%, respectively) and by color flow imaging
      (86 and 100%, respectively). Intratumoral blood vessels were detected in all
      cases with recurrent pelvic tumors, and in only one of these cases the PI was
      high. We recommend a routine follow-up with transvaginal sonography in women
      completing their treatment for pelvic tumors. When a recurrence of tumor is only
      suspected on transvaginal sonography, color flow imaging may be used as an
      additional diagnostic tool.

PMID- 7636953
TI  - Transvaginal color and pulsed Doppler study of uterine blood flow in the first
      and early second trimesters of pregnancy: normal versus abnormal.
AB  - Transvaginal color Doppler ultrasonography was used to study 131 normal early
      pregnancies, 30 molar pregnancies, 20 threatened abortions, two blighted ova, and
      five pregnancies with intramural myoma. Four separate parts of the maternal
      circulation were studied: uterine, arcuate, radial, and spiral arteries. There
      was statistical difference in the RI and PI among uterine, arcuate, radial, and
      spiral arteries (P < 0.001) in all observed groups of patients except those with
      intramural myoma. When the same part of the maternal circulation was compared
      among different groups of patients, the following results reached statistical
      significance: uterine artery in normal and molar pregnancy (P < 0.001); arcuate
      artery in normal and molar pregnancy (P < 0.001); radial artery in normal and
      molar pregnancy (P < 0.001) and in normal pregnancy and threatened abortion (P <
      0.01); spiral artery in normal and molar pregnancy (P < 0.001), in normal
      pregnancy and threatened abortion (P < 0.01), and in molar pregnancy and
      threatened abortion (P < 0.01). The standard values of blood flow are different
      in normal and in some cases of abnormal early pregnancy (molar pregnancy,
      threatened abortion).

PMID- 7636954
TI  - The early prenatal diagnosis of bilateral renal agenesis using transvaginal
      sonography and color Doppler ultrasonography.

PMID- 7636956
TI  - Spontaneous detorsion of the ovary demonstrated by ultrasonography.

PMID- 7636955
TI  - Acute idiopathic scrotal edema: role of scrotal sonography.

PMID- 7636958
TI  - Prenatal ultrasonographic demonstration of the trident hand in heterozygous
      achondroplasia.

PMID- 7636957
TI  - Characteristic findings of toxoplasmosis in utero: a case report.

PMID- 7636959
TI  - Gallbladder wall mass on sonography representing large-cell non-Hodgkin's
      lymphoma in an AIDS patient.

PMID- 7636960
TI  - Conclusions regarding biological effects of ultrasound for diagnostically
      relevant exposures.

PMID- 7636961
TI  - Infected renal cysts: sonographic diagnosis and management.
AB  - IRC are rare entities characterized by fever and unilateral flank pain resistant
      to antibiotic therapy. In our series of nine IRC in eight patients, the
      predominant sonographic finding was an abnormal echogenic texture of the cyst
      contents, in contrast to previous reports that stressed the frequency of wall
      thickening as a sign of infection. Sonographically guided cyst aspiration and
      drainage of eight cysts in seven patients provided diagnostic material and
      resulted in relief of symptoms. Although the cause of IRC is uncertain, these
      entities may be more common than previously suspected.

PMID- 7636962
TI  - The bovine herpesvirus alpha gene trans-inducing factor activates transcription
      by mechanisms different from those of its herpes simplex virus type 1 counterpart
      VP16.
AB  - In herpes simplex virus (HSV)-infected cells, viral gene expression is initiated
      when the immediate-early, or alpha, genes are transactivated by the alpha gene
      trans-inducing factor (alpha TIF), a component of the infecting virion. The
      protein binds to one or more recognition elements (TAATGARAT) in the promoters of
      alpha genes via interaction with the cellular proteins Oct-1 and CFF. The alpha
      TIF of HSV (HSV-alpha TIF) is believed to subsequently accelerate the assembly of
      the transcription complex by direct contact between its carboxyl-terminal acidic
      activation domain and at least two components of the transcription apparatus,
      TAFII40 and TFIIB. Like its HSV counterpart, the alpha TIF of bovine herpesvirus
      (BHV) (designated BHV-alpha TIF) also transactivates alpha gene promoters and for
      full activity exhibits a requirement for its extended carboxyl-terminal region.
      Despite this requirement, there is a notable lack of homology to the carboxyl
      terminal acidic activation domain of HSV-alpha TIF. We swapped the amino- and
      carboxyl-terminal domains of HSV-alpha TIF and BHV-alpha TIF to make chimeric
      proteins. Using these chimeras, we show that the carboxyl terminus of BHV-alpha
      TIF is insufficient for transactivation, which requires cooperative determinants
      in both the amino-terminal and carboxyl-terminal regions of the protein. We have
      previously shown that the amino-terminal determinant in BHV-alpha TIF displays
      reduced but significant independent transactivation potential. Interestingly,
      this amino-terminal determinant appears not to reside in the HSV-alpha TIF, which
      displays no independent amino-terminal activity. Furthermore, we show that the
      amino-terminal activation domain of BHV-alpha TIF may be able to act
      synergistically with the carboxyl-terminal activation domain of HSV-alpha TIF,
      since a chimeric protein containing both domains appeared to be more efficient at
      activating transcription than either alpha TIF. In addition, the amino terminus
      of HSV-alpha TIF could not restore activity when linked to the carboxyl terminus
      of BHV-alpha TIF, while the amino terminus of BHV-alpha TIF reconstituted an
      intact protein with potent activation potential. We also show that in fusions
      with the DNA binding domain of GAL4, full activity requires the entire BHV-alpha
      TIF, although both amino and carboxyl termini display some activity on their own.
      In contrast, for HSV-alpha TIF, the carboxyl terminus is sufficient and possibly
      even more potent than the entire protein, while the amino-terminus is devoid of
      activity.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7636963
TI  - A single amino acid change in the cytoplasmic domain of the simian
      immunodeficiency virus transmembrane molecule increases envelope glycoprotein
      expression on infected cells.
AB  - We have described a virus termed CP-MAC, derived from the BK28 molecular clone of
      simian immunodeficiency virus, that was remarkable for its ability to infect Sup
      T1 cells with rapid kinetics, cell fusion, and CD4 down-modulation (C. C.
      LaBranche, M. M. Sauter, B. S. Haggarty, P. J. Vance, J. Romano, T. K. Hart, P.
      J. Bugelski, and J. A. Hoxie, J. Virol. 68:5509-5522, 1994 [Erratum 68:7665
      7667]). Compared with BK28, CP-MAC exhibited a number of changes in its envelope
      glycoproteins, including a highly stable association between the external (SU)
      and transmembrane (TM) molecules, a more rapid electrophoretic mobility of TM,
      and, of particular interest, a marked increase in the level of envelope protein
      expression on the surface of infected cells. These changes were shown to be
      associated with 11 coding mutations in the env gene (5 in SU and 6 in TM). In
      this report, we demonstrate that a single amino acid mutation of a Tyr to a Cys
      at position 723 (Y723C) in the TM cytoplasmic domain of CP-MAC is the principal
      determinant for the increased expression of envelope glycoproteins on the cell
      surface. When introduced into the env gene of BK28, the Y723C mutation produced
      up to a 25-fold increase in the levels of SU and TM on chronically infected
      cells, as determined by fluorescence-activated cell sorter analysis with
      monoclonal and polyclonal antibodies. A similar effect was observed when a Tyr-to
      Cys change was introduced at the analogous position (amino acid 721) in the
      SIVmac239 molecular clone, which, unlike BK28 does not contain a premature stop
      codon in its TM cytoplasmic tail. Substituting other amino acids, including Ala,
      Ile, and Ser, at this position produced increases in surface envelope
      glycoproteins that were similar to that observed for the Cys substitution, while
      a Tyr-to-Phe mutation produced a smaller increase. These results could not be
      accounted for by differences in the kinetics or efficiency of envelope
      glycoprotein processing or by shedding of SU from infected cells. However,
      immunoelectron microscopy demonstrated that the Y723C mutation in BK28 produced a
      striking redistribution of cell surface envelope molecules from localized patches
      to a diffuse pattern that covered the entire plasma membrane. This finding
      suggests that mutation of a Tyr residue in the simian immunodeficiency virus TM
      cytoplasmic domain may disrupt a structural element that can modulate envelope
      glycoprotein expression on the surface of infected cells.

PMID- 7636965
TI  - Tropism of varicella-zoster virus for human CD4+ and CD8+ T lymphocytes and
      epidermal cells in SCID-hu mice.
AB  - To investigate the cell tropism and pathogenicity of varicella-zoster virus (VZV)
      strains, we analyzed VZV replication by using SCID-hu mice that carry human fetal
      thymus/liver implants under the kidney capsule or as subcutaneous fetal skin
      implants. MRC-5 cells infected with wild-type VZV or the Oka strain, used in the
      live attenuated varicella vaccine, were injected into the implants. The implants
      were surgically removed 2, 7, 14, and 21 days postinfection. The VZV titer from
      infected thymus/liver implants peaked on day 7 for the wild-type strain and on
      day 14 for the Oka strain. Histological analysis showed necrotic areas
      characterized by thymocyte depletion and fibrosis. VZV protein synthesis was
      detectable by immunohistochemical staining in the necrotic areas and in distant
      regions that did not show cytopathic changes, and VZV DNA was detected by in situ
      hybridization in the same distribution. Fluorescence-activated cell sorting
      analysis of thymocytes harvested at day 7 postinfection showed that VZV proteins
      were expressed in CD4+, CD8+, and CD4+ CD8+ T cells; VZV was cultured from each T
      cell subpopulation. The Oka strain had tropism for human cell types similar to
      that of wild-type VZV. T lymphocytes released infectious VZV, which is a novel
      and important observation about the replication of this otherwise highly cell
      associated virus. VZV-infected skin implants exhibited microscopic epidermal
      lesions that were indistinguishable histologically from the characteristic
      lesions of varicella. These experiments demonstrate a unique tropism of VZV for
      human T lymphocytes, explaining its capacity to cause viremia in natural disease,
      and demonstrate the value of the SCID-hu model for studies of VZV pathogenesis.

PMID- 7636964
TI  - In vitro selection and characterization of human immunodeficiency virus type 1
      (HIV-1) isolates with reduced sensitivity to hydroxyethylamino sulfonamide
      inhibitors of HIV-1 aspartyl protease.
AB  - Human immunodeficiency virus type 1 (HIV-1) variants with reduced sensitivity to
      the hydroxyethylamino sulfonamide protease inhibitors VB-11,328 and VX-478 have
      been selected in vitro by two independent serial passage protocols with HIV-1 in
      CEM-SS and MT-4 cell lines. Virus populations with greater than 100-fold
      increased resistance to both inhibitors compared with the parental virus have
      been obtained. DNA sequence analyses of the protease genes from VB-11,328- and VX
      478-resistant variants reveal a sequential accumulation of point mutations, with
      similar resistance patterns occurring for the two inhibitors. The deduced amino
      acid substitutions in the resistant protease are Leu-10-->Phe, Met-46-->Ile, Ile
      47-->Val, and Ile-50-->Val. This is the first observation in HIV protease
      resistance studies of an Ile-50-->Val mutation, a mutation that appears to arise
      uniquely against the sulfonamide inhibitor class. When the substitutions observed
      were introduced as single mutations into an HIV-1 infectious clone (HXB2), only
      the Ile-50-->Val mutant showed reduced sensitivity (two- to threefold) to VB
      11,328 and VX-478. A triple protease mutant infectious clone carrying the
      mutations Met-46-->Ile, Ile-47-->Val, and Ile-50-->Val, however, showed much
      greater reduction in sensitivity (14- to 20-fold) to VB-11,328 and VX-478. The
      same mutations were studied in recombinant HIV protease. The mutant protease Ile
      50-->Val displays a much lower affinity for the inhibitors than the parent enzyme
      (< or = 80-fold). The protease triply mutated at Met-46-->Ile, Ile-47-->Val, and
      Ile-50-->Val shows an even greater decrease in inhibitor binding (< or = 270
      fold). The sulfonamide-resistant HIV protease variants remain sensitive to
      inhibitors from other chemical classes (Ro 31-8959 and L-735,524), suggesting
      possibilities for clinical use of HIV protease inhibitors in combination or
      serially.

PMID- 7636968
TI  - Involvement of a spliced and defective human foamy virus in the establishment of
      chronic infection.
AB  - Human foamy retrovirus (HFV) is found as two proviruses (HFV and delta HFV) which
      differ by a splice-induced deletion within the bel1 transactivator gene. The
      defective delta HFV (which lacks a functional Bel1 but harbors an intronless bet
      gene) is predominantly found in nonlytic infections in vitro as well as in vivo.
      Here, we show that infection of cell lines stably transduced by delta HFV DNA
      with the highly lytic HFV leads to chronic infections characterized by an absence
      of lysis, a balanced ratio of HFV to delta HFV, and a persistent Bet expression
      accompanied by a shutoff of structural genes. While this system only partially
      reflects the natural situation, in which target cells are infected by HFV and
      delta HFV simultaneously, it strongly suggests that delta HFV is a defective
      interfering retrovirus. Accordingly, previous or concomitant exposure to delta
      HFV viruses greatly enhances the formation of lysis-resistant clones in culture
      after HFV infection. The inability of delta HFV proviruses encoding a mutated bet
      gene to induce chronic infection suggests a role for Bet in this process. Through
      a specific, splice-induced, genomic deletion, resulting in a switch from Bel1 to
      Bet expression, the lytic properties of HFV are progressively lost. Such
      programmed inactivation of a key gene represents a new regulatory mechanism of
      gene expression in retroviruses.

PMID- 7636967
TI  - Pattern of disease after murine hepatitis virus strain 3 infection correlates
      with macrophage activation and not viral replication.
AB  - Murine hepatitis virus strain (MHV-3) produces a strain-dependent pattern of
      disease which has been used as a model for fulminant viral hepatitis. This study
      was undertaken to examine whether there was a correlation between macrophage
      activation and susceptibility or resistance to MHV-3 infection. Peritoneal
      macrophages were isolated from resistant A/J and susceptible BALB/cJ mice and,
      following stimulation with MHV-3 or lipopolysaccharide (LPS), analyzed for
      transcription of mRNA and production of interleukin-1 (IL-1), tumor necrosis
      factor alpha (TNF-alpha), transforming growth factor beta (TGF-beta), mouse
      fibrinogen-like protein (musfiblp), tissue factor (TF), leukotriene B4, and
      prostaglandin E2 (PGE2). Macrophages from BALB/cJ mice produced greater amounts
      of IL-1, TNF-alpha, TGF-beta, leukotriene B4, and musfiblp following MHV-3
      infection than macrophages from resistant A/J mice, whereas in response to LPS,
      equivalent amounts of IL-1, TNF-alpha, TGF-beta, and TF were produced by
      macrophages from both strains of mice. Levels of mRNA of IL-1, TNF-alpha, and
      musfiblp were greater and more persistent in BALB/cJ than in A/J macrophages,
      whereas the levels and kinetics of IL-1, TNF-alpha, and TF mRNA following LPS
      stimulation were identical in macrophages from both strains of mice. Levels of
      production of PGE2 by MHV-3-stimulated macrophages from resistant and susceptible
      mice were equivalent; however, the time course for induction of PGE2, differed,
      but the total quantity of PGE2 produced was insufficient to inhibit induction of
      musfiblp, a procoagulant known to correlate with development of fulminant hepatic
      necrosis in susceptible mice. These results demonstrate marked differences in
      production of inflammatory mediators to MHV-3 infection in macrophages from
      resistant A/J and susceptible BALB/cJ mice, which may explain the marked hepatic
      necrosis and fibrin deposition and account for the lethality of MHV-3 in
      susceptible mice.

PMID- 7636966
TI  - Myxoma virus induces extensive CD4 downregulation and dissociation of p56lck in
      infected rabbit CD4+ T lymphocytes.
AB  - Myxoma virus is a pathogenic poxvirus that induces extensive dysregulation of
      cellular immunity in infected European rabbits. Infection of a rabbit CD4+ T-cell
      line (RL-5) with myxoma virus results in dramatic reductions of cell surface
      levels of CD4 as monitored by flow cytometry. The virus-induced downregulation of
      CD4 requires early but not late viral gene expression and could not be inhibited
      by staurosporine, an inhibitor of protein kinase C, which effectively blocks
      phorbol 12-myristate-13-acetate-induced downregulation of CD4. The decrease in
      total cellular levels of CD4 during myxoma virus infection could be inhibited by
      the lysosomotrophic agent NH4Cl, suggesting a lysosomal fate for CD4 during
      myxoma virus infection. Steady-state levels of the CD4-associated protein
      tyrosine kinase p56lck remained unchanged during myxoma virus infection,
      suggesting that p56lck dissociates from CD4 prior to CD4 degradation in virus
      infected cells. Total p56lck kinase activity was unaffected during myxoma virus
      infection, although the amount of p56lck physically associated with CD4 declined
      in parallel with the loss of CD4. Thus, myxoma virus infection of CD4+ T
      lymphocytes triggers CD4 downregulation via a protein kinase C-independent
      pathway, causing the dissociation of p56lck and the degradation of CD4 in
      lysosomal vesicles.

PMID- 7636969
TI  - Membrane protein molecules of transmissible gastroenteritis coronavirus also
      expose the carboxy-terminal region on the external surface of the virion.
AB  - The binding domains of four monoclonal antibodies (MAbs) specific for the M
      protein of the PUR46-MAD strain of transmissible gastroenteritis coronavirus
      (TGEV) have been located in the 46 carboxy-terminal amino acids of the protein by
      studying the binding of MAbs to recombinant M protein fragments. Immunoelectron
      microscopy using these MAbs demonstrated that in a significant proportion of the
      M protein molecules, the carboxy terminus is exposed on the external surface both
      in purified viruses and in nascent TGEV virions that recently exited infected
      swine testis cells. The same MAbs specifically neutralized the infectivity of the
      PUR46-MAD strain, indicating that the C-terminal domain of M protein is exposed
      on infectious viruses. This topology of TGEV M protein probably coexists with the
      structure currently described for the M protein of coronaviruses, which consists
      of an exposed amino terminus and an intravirion carboxy-terminal domain. The
      presence of a detectable number of M protein molecules with their carboxy termini
      exposed on the surface of the virion has relevance for viral function, since it
      has been shown that the carboxy terminus of M protein is immunodominant and that
      antibodies specific for this domain both neutralize TGEV and mediate the
      complement-dependent lysis of TGEV-infected cells.

PMID- 7636970
TI  - Mapping of mutations contributing to the temperature sensitivity of the Sabin 1
      vaccine strain of poliovirus.
AB  - The temperature-sensitive and attenuated phenotypes of the Sabin type 1 vaccine
      strain of poliovirus result from numerous point mutations which occurred in the
      virulent Mahoney virus parent. One of these mutations is located in a 3D
      polymerase (3Dpol) codon (U-6203-->C, Tyr-73-->His) and is involved in
      attenuation in common mice (M. Tardy-Panit, B. Blondel, A. Martin, F. Tekaia, F.
      Horaud, and F. Delpeyroux, J. Virol. 67:4630-4638, 1993). This mutation also
      appears to contribute to temperature sensitivity, in association with at least 1
      other of the 10 mutations of the 3'-terminal part of the genome including the
      3Dpol coding and 3' noncoding regions. To map the other mutation(s), we
      constructed poliovirus mutants by mutagenesis and recombination of Mahoney and
      Sabin 1 cDNAs. Characterization of these poliovirus mutants showed that a second
      mutation in a 3Dpol codon (C-7071-->U, Thr-362-->Ile) contributes to temperature
      sensitivity. A mutation in the 3' noncoding region of the genome (A-7441-->G),
      alone or linked to another mutation (U-7410-->C), also appeared to be involved in
      this phenotype. The temperature-sensitive effect associated with the 3'-terminal
      part of the Sabin 1 genome results from the cumulative and/or synergistic effects
      of at least three genetic determinants, i.e., the His-73 and Ile-362 codons of
      3Dpol and nucleotide G-7441. Sequence analysis of strains isolated from patients
      with vaccine-associated paralytic poliomyelitis showed that these genetic
      determinants are selected against in vivo, although the Ile-362 codon appeared to
      be more stable than either the His-73 codon or G-7441. These genetic determinants
      may contribute to the safety of Sabin 1 in vaccines.

PMID- 7636971
TI  - Expression of PE38 and IE2, viral members of the C3HC4 finger family, during
      baculovirus infection: PE38 and IE2 localize to distinct nuclear regions.
AB  - The pe38 gene of Autographa californica nuclear polyhedrosis virus represents one
      of the major early transcripts after viral infection. The function of the pe38
      protein, which contains a C3HC4 zinc finger motif, is still not understood. We
      have raised polyclonal antiserum against the pe38 protein, PE38, produced in
      bacteria to investigate pe38 expression in the course of infection. A
      approximately 38-kDa polypeptide is first detectable at 2 h postinfection and
      decreases rapidly after 24 h. During the late phases of infection, a smaller
      protein of approximately 20 kDa which cross-reacts with the PE38-specific
      antiserum is visible at a constant level until 120 h postinfection. Since the
      pe38 gene shares a divergent promoter unit with the ie2 gene (formerly IEN), we
      have compared the expressions of the two genes. Polyclonal antibodies were raised
      against the bacterially expressed ie2 protein. The temporal expression pattern of
      the approximately 49-kDa ie2 protein is comparable to that of the approximately
      38-kDa pe38 protein. Furthermore, both proteins are present in the nuclear
      fraction of A. californica nuclear polyhedrosis virus-infected Spodoptera
      frugiperda cells, but the approximately 38-kDa pe38 protein is also detectable in
      the cytoplasm while the smaller protein of approximately 20 kDa is exclusively
      present in the cytoplasmic fraction. Immunofluorescence analysis reveals that
      PE38 and IE2 localize to distinct regions within the nucleus mainly detected
      after transfection of pe38- and ie2-expressing constructs.

PMID- 7636972
TI  - Failure of the bovine papillomavirus to transform mouse embryo fibroblasts with a
      targeted disruption of the insulin-like growth factor I receptor genes.
AB  - Mouse embryo cells with a targeted disruption of the insulin-like growth factor I
      receptor (IGF-IR) genes (R- cells) are refractory to transformation by the simian
      virus 40 large T antigen and/or an activated and overexpressed Ras, both of which
      readily transform cells from wild-type littermate embryos and other 3T3-like
      cells. R- cells are also refractory to transformation induced by overexpressed
      epidermal growth factor receptor and platelet-derived growth factor receptor
      beta. Since the platelet-derived growth factor receptor beta is required for
      transformation by bovine papillomavirus, we inquired whether the IGF-IR was also
      required for transformation by bovine papillomavirus E5 oncoprotein. We show here
      that R- cells are refractory to transformation by E5; reintroduction into R-
      cells of a human IGF-IR restores the susceptibility to transformation.

PMID- 7636973
TI  - The human cytomegalovirus UL98 gene transcription unit overlaps with the pp28
      true late gene (UL99) and encodes a 58-kilodalton early protein.
AB  - A murine monoclonal antibody (I2) reacts strongly with the nucleus of human
      cytomegalovirus (HCMV)-infected human fibroblasts. Western blot (immunoblot)
      analysis using I2 demonstrated that a protein with an apparent molecular mass of
      58-kDa (E58) was expressed at 5 h after infection, and levels increased through
      72 h. Immunoblot screening of an early cDNA expression library resulted in a
      positive clone which hybridized to the right end of the XbaI C fragment of the
      HCMV Towne strain. Further analysis demonstrated that the E58-specific clone was
      homologous to the putative UL98 open reading frame, which has been proposed to
      encode the viral alkaline exonuclease homolog. RNA analysis demonstrated a 3.0-kb
      RNA which is expressed at early times after infection, as well as in the absence
      of viral DNA replication, and which is 3' coterminal with the pp28 (UL99) gene
      region. Insertion of the UL98 genomic sequence into a eucaryotic expression
      vector and subsequent Western blot analysis using I2 demonstrated that the
      expressed protein comigrated with E58 from infected cells. E58 also reacts
      specifically with a previously described antibody, anti-P2-1, which was proposed
      to recognize a putative late 58-kDa protein. E58 comigrates with the putative
      late 58-kDa protein, indicating that these two proteins are likely the same.
      Analysis of the UL98 promoter revealed a TATATAA sequence located at nucleotide
      142525. Insertion of the putative promoter 5' to a reporter gene demonstrated
      that the UL98 promoter was activated in cotransfection experiments with IE1 and
      IE2 proteins. These studies demonstrate that UL98 is a bona fide early gene,
      which is consistent with its probable role as the viral alkaline exonuclease
      gene.

PMID- 7636974
TI  - Intermediates of adeno-associated virus type 2 assembly: identification of
      soluble complexes containing Rep and Cap proteins.
AB  - The proteins encoded by the adeno-associated virus type 2 (AAV-2) rep and cap
      genes obtained during a productive infection of HeLa cells with AAV-2 and
      adenovirus type 2 were fractionated according to solubility, cellular
      localization, and sedimentation properties. The majority of Rep and Cap proteins
      accumulated in the nucleus, where they distributed into a soluble and an
      insoluble fraction. Analysis of the soluble nuclear fraction of capsid proteins
      by sucrose density gradients showed that they formed at least three steady-state
      pools: a monomer pool sedimenting at about 6S, a pool of oligomeric intermediates
      sedimenting between 10 and 15S, and a broad pool of assembly products with a peak
      between 60 and 110S, the known sedimentation positions of empty and full capsids.
      While the soluble nuclear monomer and oligomer pool contained predominantly only
      two capsid proteins, the 30 to 180S assembly products contained VP1, VP2, and VP3
      in a stoichiometry similar to that of purified virions. They probably represent
      different intermediates in capsid assembly, DNA encapsidation, and capsid
      maturation. In contrast, the cytoplasmic fraction of capsid proteins showed a
      pattern of oligomers continuously increasing in size without a defined peak,
      suggesting that assembly of 60S particles occurs in the nucleus. Soluble nuclear
      Rep proteins were distributed over the whole sedimentation range, probably as a
      result of association with AAV DNA. Subfractions of the Rep proteins with defined
      sedimentation values were obtained in the soluble nuclear and cytoplasmic
      fractions. We were able to coimmunoprecipitate capsid proteins sedimenting
      between 60 and 110S with antibodies against Rep proteins, suggesting that they
      exist in common complexes possibly involved in AAV DNA packaging. Antibodies
      against the capsid proteins, however, precipitated Rep78 and Rep68 predominantly
      with a peak around 30S representing a second complex containing Rep and Cap
      proteins.

PMID- 7636975
TI  - Nucleotide sequence and protein analysis of a complex piscine retrovirus, walleye
      dermal sarcoma virus.
AB  - Walleye dermal sarcoma virus (WDSV) is a fish retrovirus associated with the
      development of tumors in walleyes. We have determined the complete nucleotide
      sequence of a DNA clone of WDSV, the N-terminal amino acid sequences of the major
      proteins, and the start site for transcription. The long terminal repeat is 590
      bp in length, with the U3 region containing consensus sequences likely to be
      involved in viral gene expression. A predicted histidyl-tRNA binding site is
      located 3 nucleotides distal to the 3' end of the long terminal repeat. Virus
      particles purified by isopycnic sedimentation followed by rate zonal
      sedimentation showed major polypeptides with molecular sizes of 90, 25, 20, 14,
      and 10 kDa. N-terminal sequencing of these allowed unambiguous assignment of the
      small polypeptides as products of the gag gene, including CA and NC, and the
      large polypeptide as the TM product of env. The 582-amino-acid (aa) Gag protein
      precursor is predicted to be myristylated as is found for most retroviruses. NC
      contains a single Cys-His motif like those found in all retroviruses except
      spumaviruses. The WDSV pro and pol genes are in the same translational reading
      frame as gag and thus apparently are translated after termination suppression.
      The env gene encodes a surface (SU) protein of 469 aa predicted to be highly
      glycosylated and a large transmembrane (TM) protein of 754 aa. The sequence of TM
      is unusual in that it ends in a very hydrophobic segment of 65 residues
      containing a single charged residue. Following the env gene are two
      nonoverlapping long open reading frames of 290 aa (orf-A) and 306 aa (orf-B),
      neither of which shows significant sequence similarity with known genes. A third
      open reading frame of 119 aa (orf-C) is located in the leader region preceding
      gag. The predicted amino acid sequence of reverse transcriptase would place WDSV
      phylogenetically closest to the murine leukemia virus-related genus of
      retroviruses. However, other members of this genus do not have accessory genes,
      suggesting that WDSV acquired orf-A, orf-B, and perhaps orf-C late in its
      evolution. We hypothesize by analogy with other complex retroviruses that the
      accessory genes of WDSV function in the regulation of transcription and in RNA
      processing and also in the induction of walleye dermal sarcoma.

PMID- 7636976
TI  - Large hepatitis delta antigen in packaging and replication inhibition: role of
      the carboxyl-terminal 19 amino acids and amino-terminal sequences.
AB  - Hepatitis delta virus (HDV) encodes two proteins, the small delta antigen (SHDAg)
      and large delta antigen (LHDAg). The latter is identical to the former except for
      the presence of additional 19 amino acids at the C terminus. While SHDAg is
      required for HDV replication, LHDAg inhibits replication and, together with
      hepatitis B surface antigen (HBsAg), is required for the assembly of HDV. The
      last 19 C-terminal amino acids of LHDAg are essential for HDV assembly. Most of
      LHDAg (amino acids 19 to 146 and 163 to 195) had been shown to be dispensable for
      packaging with HBsAg. To discern whether the last 19 C-terminal amino acids
      solely constitute the signal for packaging with HBsAg, we constructed two LHDAg
      deletion mutants and tested their abilities to be packaged with HBsAg in
      cotransfection experiments. We found that deletion of amino acids 2 to 21 and 142
      to 165 did not affect LHDAg packaging. This result suggested that only the last
      19 C-terminal amino acids of LHDAg are required for packaging. We further
      constructed two plasmids which expressed c-H-ras with or without additional 19 C
      terminal amino acids identical to those in LHDAg. Only c-H-ras with additional 19
      amino acids could be cosecreted with HBsAg in the cotransfection experiment. This
      result confirmed that the C-terminal 19 amino acids are the packaging signal for
      HBsAg. We also tested the trans activation activity and trans-dominant inhibitory
      activity of the deletion mutants of SHDAg and LHDAg, respectively. In contrast to
      deletion of amino acids 142 to 165, deletion of amino acids 2 to 21 impaired the
      trans-dominant inhibitory activity of LHDAg. Deletion of amino acids 2 to 21 and
      142 to 165 did not affect the trans activation activity of SHDAg. This result
      suggested that a functional domain which is important for the trans-dominant
      inhibitory activity of LHDAg exists in the amino terminus of HDAg.

PMID- 7636977
TI  - C/EBP proteins activate transcription from the human immunodeficiency virus type
      1 long terminal repeat in macrophages/monocytes.
AB  - Three binding sites for C/EBP proteins are found in the human immunodeficiency
      virus type 1 (HIV-1) long terminal repeat (LTR) (V. M. Tesmer, A. Rajadhyaksha,
      J. Babin, and M. Bina, Proc. Natl. Acad. Sci. USA 90:7298-7302, 1993). We have
      determined the functional role of C/EBP proteins and C/EBP sites in regulating
      transcription from the HIV-1 LTR in monocytes/macrophages. Inhibition of
      endogenous C/EBP proteins, using either an excess of C/EBP binding sites or a
      trans-dominant negative inhibitor, demonstrated that C/EBP proteins are required
      for basal and activated levels of HIV-1 LTR transcription in the promonocytic
      cell line U937. Northern (RNA) blots and binding assays showed that NF-IL6 is the
      only known C/EBP family member which is increased when U937 cells are activated.
      Mutational analyses of the HIV-1 LTR showed that one C/EBP site is required for
      normal LTR transcription both before and after cellular activation and that the
      two 3' C/EBP sites are functionally equivalent. However, transcription from
      crippled HIV-1 LTRs lacking C/EBP sites can still be induced following activation
      of U937 cells. Several models are suggested for how elevated NF-IL6 may
      participate in an autostimulatory loop involving HIV infection, macrophage
      activation, cytokine expression, and HIV replication.

PMID- 7636978
TI  - Identification of gene products encoded by the latency-related gene of bovine
      herpesvirus 1.
AB  - Bovine herpesvirus 1 (BHV-1) establishes a latent infection in sensory ganglionic
      neurons of infected animals. Expression of latency-related (LR) gene products is
      controlled by a 980-bp fragment (LR promoter). DNA sequence analysis revealed
      that two major open reading frames (ORFs) are in the LR gene. Antibodies directed
      against both ORFs were generated in rabbits by using synthetic peptides. Antibody
      P2, which is directed to sequences near the amino terminus of ORF 2, recognized a
      41-kDa protein in lytically infected cells, suggesting that ORF 2 encodes a
      protein. When the LR gene was inserted into a mammalian expression vector and
      subsequently transfected into COS-7 cells, a 41-kDa protein was detected by use
      of silver-stained sodium dodecyl sulfate-polyacrylamide gels and by the P2
      antibody. In contrast, this protein was not detected in mock-transfected cells.
      Deletion of DNA sequences containing ORF 2 blocked synthesis of the 41-kDa
      protein in COS-7 cells. Reverse transcriptase-mediated PCRs indicated that
      splicing occurs near the C terminus of ORF 2. Further studies indicated that LR
      RNA was alternatively spliced in latently infected cattle and that a fraction of
      LR RNA was poly(A)+. Taken together, these studies suggested that a spliced LR
      transcript has the potential to encode a 41-kDa protein.

PMID- 7636980
TI  - Regulation of human cytomegalovirus US3 gene transcription by a cis-repressive
      sequence.
AB  - Regulation of immediate-early gene expression in human cytomegalovirus is subject
      to complex controls. The major immediate-early (mIE) gene is regulated by both
      positive and negative regulatory signals, including autoregulation mediated by a
      cis-repressive sequence. A second immediate-early gene, the US3 gene, is
      transcribed with kinetic similar to those of the mIE gene. I have identified an
      element present in the US3 gene located from -1 to -13 (relative to the start
      site of transcription) that mediates a decrease in US3 transcription. The US3
      element resembles the cis-repressive element of the mIE gene in sequence,
      position, and function. The common theme of negative regulation of immediate
      early genes shortly after infection suggests that a decrease in the level of
      immediate-early proteins may be critical for viral replication.

PMID- 7636979
TI  - The vaccinia virus D5 protein, which is required for DNA replication, is a
      nucleic acid-independent nucleoside triphosphatase.
AB  - The vaccinia virus D5 gene encodes a 90-kDa protein that is transiently expressed
      at early times after infection. Temperature-sensitive mutants with lesions in the
      D5 gene exhibit a fast-stop DNA- phenotype and are also impaired in homologous
      recombination. Here we report the overexpression of the D5 protein within the
      context of a vaccinia virus infection and its purification to apparent
      homogeneity. The purified protein has an intrinsic nucleoside triphosphatase
      activity which is independent of, and not stimulated by, any common nucleic acid
      cofactors. All eight common ribo- and deoxyribonucleoside triphosphates are
      hydrolyzed to the diphosphate form in the presence of a divalent cation.
      Implications for the role of D5 in viral DNA replication are addressed.

PMID- 7636981
TI  - Transcriptional enhancer activity of hr5 requires dual-palindrome half sites that
      mediate binding of a dimeric form of the baculovirus transregulator IE1.
AB  - The hr5 enhancer element stimulates early viral transcription and may function as
      an origin of DNA replication for Autographa californica nuclear polyhedrosis
      virus (AcMNPV). The smallest functional unit of hr5 is a 28-bp repeat consisting
      of an imperfect palindrome (28-mer). To identify essential sequences and examine
      the molecular basis of hr5 activity, the effects of site-directed mutations on
      transcriptional enhancement by the 28-mer and binding of the AcMNPV
      transregulator IE1 were investigated. In transfection assays and infections with
      AcMNPV recombinants, activation of a basal viral promoter required sequences
      within both halves of the 28-mer. Basal promoter activation also required a
      critical spacing between these half sites. Mobility shift assays indicated that
      hr5 probes containing a single 28-mer were bound by in vitro-synthesized IE1.
      Competition assays using DNA fragments that contained mutated 28-mers
      demonstrated that both half sites were required for optimal binding of IE1.
      Similar assays using mutated 28-mer DNAs and nuclear extracts indicated that the
      relative affinity with which AcMNPV infection-specific proteins bound to the 28
      mer was similar to that of in vitro-synthesized IE1. By using a combination of
      DNA binding and antibody supershift assays, it was demonstrated that IE1 binds to
      the 28-mer as a dimer. Collectively, these findings support a model in which
      symmetrical IE1 binding and simultaneous interaction with each half site are
      required for IE1-mediated transcriptional enhancement by hr5. Thus, sequence
      specific binding may be one of the mechanisms by which IE1 directly or indirectly
      transregulates baculovirus gene expression.

PMID- 7636982
TI  - The foot-and-mouth disease virus leader proteinase gene is not required for viral
      replication.
AB  - The foot-and-mouth disease virus (FMDV) leader (L) proteinase has only two known
      functions: (i) autocatalytic removal from the N terminus of the viral polyprotein
      and (ii) cleavage of the p220 subunit of the eukaryotic initiation factor 4F
      complex, which helps to shut off host protein synthesis. Cleavage of p220 appears
      to be important for picornavirus replication, since rhinoviruses and
      enteroviruses utilize a different proteinase (2A) to cleave p220. To explore the
      role of L in FMDV replication, we generated synthetic FMDV genomes lacking the L
      gene and tested their viability in cells. Genomes were constructed with the N
      terminal Gly codon of VP4 positioned directly following either the first (Lab) or
      second (Lb) Met codon of the L protein. Cells transfected with synthetic RNAs
      lacking L and initiating with the Lab Met codon failed to produce viable virus,
      but cells transfected with RNAs that utilized the second AUG to drive translation
      of the viral polyprotein produced viable viruses. These leader-deleted viruses
      produced plaques on BHK cells that were slightly smaller than those produced by
      wild-type (WT) virus, grew to slightly lower titers than WT virus in BHK cells,
      shut off host protein synthesis more slowly than WT virus, and were slightly
      attenuated in mice. These studies indicate that the L proteinase is not essential
      for FMDV replication and show that in the cells and animals tested the L gene has
      a limited effect on virus replication.

PMID- 7636983
TI  - Avian I kappa B alpha is transcriptionally induced by c-Rel and v-Rel with
      different kinetics.
AB  - The Rel/NF-kappa B family of transcription factors participates in the regulation
      of genes involved in defense responses, inflammation, healing and regeneration
      processes, and embryogenesis. The control of the transcriptional activation
      potential of the Rel/NF-kappa B proteins is mediated, in part, by their
      association with inhibitory proteins of the I kappa B family. This association
      results in the cytoplasmic retention of these factors until the cell receives a
      proper stimulatory signal. The I kappa B alpha gene is a target for regulation by
      the Rel/NF-kappa B proteins and is in fact upregulated in response to Rel/NF
      kappa B activation. A naturally occurring oncogenic variant of the Rel/NF-kappa B
      family, v-rel, transforms avian lymphocytes, bone marrow cells, monocytes, and
      fibroblasts. Avian I kappa B alpha expression is upregulated in cells transformed
      by v-Rel. Avian I kappa B alpha is also upregulated in fibroblasts overexpressing
      c-Rel and oncogenic variants of c-Rel. c-Rel, a carboxy-terminally truncated
      variant of c-Rel, and v-Rel are all able to directly transactivate the expression
      of the avian I kappa B alpha gene. However, c-Rel was the most potent activator
      of this gene, and the induction of I kappa B alpha expression showed faster
      kinetics in cells overexpressing c-Rel than in those overexpressing v-Rel. The
      regulation of I kappa B alpha induction by the Rel proteins was shown to be
      dependent on a 362-bp region of the I kappa B alpha promoter that contains two
      potential NF-kappa B binding sites and one AP-1-like binding site. Results of
      electrophoretic mobility shift assays using these NF-kappa B binding sites
      indicate that major changes in the profile of DNA binding complexes in
      fibroblasts overexpressing v-Rel correlated temporally with the kinetic changes
      in v-Rel's ability to activate the expression of the I kappa B alpha gene.

PMID- 7636984
TI  - Human cytomegalovirus upregulates NF-kappa B activity by transactivating the NF
      kappa B p105/p50 and p65 promoters.
AB  - During human cytomegalovirus (HCMV) infection, a series of regulated events take
      place following virus binding and entry into the cell, including the upregulation
      of cellular transcription factors, such as NF-kappa B, which play an essential
      role in the viral life cycle. We show here that NF-kappa B message is induced
      during HCMV infection and that the induction is biphasic, suggesting an initial
      induction at immediate-early (IE) times and a second round of induction at early
      times. This hypothesis is supported by experiments using cyclohexamide, which
      showed that the first tier of induction was drug insensitive, while the second
      tier was drug sensitive. We then show that virus binding alone is sufficient to
      stimulate NF-kappa DNA binding activity, supporting its role in the initial
      induction of NF-kappa B. To begin to elucidate the mechanism(s) for the second
      tier of NF-kappa B regulation, we examined promoter constructs from the NF-kappa
      B subunits (p105/p50 and p65) for responsiveness following HCMV infection. HCMV
      infection transactivated the p105/p50 and p65 promoters. The viral IE proteins
      (IE1-72, IE2-55, and IE2-86) are expressed during the time we see NF-kappa B
      induction, so we examined their role in NF-kappa B induction. The IE1-72, IE2-55,
      and IE2-86 proteins transactivated the p65 promoter, while only the IE2-55
      protein transactivated the p105/p50 promoter. The p105/p50 promoter has NF-kappa
      B sites; therefore, upregulation could also be caused by an autoregulatory
      mechanism. The p65 promoter, however, has been demonstrated to contain only Sp1
      sites. To investigate the potential role of SP1, we examined nuclear extracts
      from HCMV-infected cells. Here, we show that there is a biphasic increase in SP1
      activity during viral infection and that there is apparently an absolute
      requirement for SP1 in the transactivation of the p65 promoter. In conclusion, we
      suggest a model in which the initial induction of NF-kappa B occurs through viral
      modulation of cellular factors and the sustained levels of NF-kappa B induction
      are regulated by a combination of cellular and viral factors.

PMID- 7636985
TI  - Herpes simplex virus glycoprotein K promotes egress of virus particles.
AB  - Herpes simplex virus (HSV) glycoprotein K (gK) is thought to be intimately
      involved in the process by which infected cells fuse because HSV syncytial
      mutations frequently alter the gK (UL53) gene. Previously, we characterized gK
      produced in cells infected with wild-type HSV or syncytial HSV mutants and found
      that the glycoprotein was localized to nuclear and endoplasmic reticulum
      membranes and did not reach the cell surface (L. Hutchinson, C. Roop, and D. C.
      Johnson, J. Virol. 69:4556-4563, 1995). In this study, we have characterized a
      mutant HSV type 1, denoted F-gK beta, in which a lacZ gene cassette was inserted
      into the gK coding sequences. Since gK was found to be essential for virus
      replication, F-gK beta was propagated on complementing cells which can express
      gK. F-gK beta produced normal plaques bounded by nonfused cells when plated on
      complementing cells, although syncytia were observed when the cells produced
      smaller amounts of gK. In contrast, F-gK beta produced only microscopic plaques
      on Vero cells and normal human fibroblasts (which do not express gK) and these
      plaques were reduced by 10(2) to 10(6) in number. Further, large numbers of
      nonenveloped capsids accumulated in the cytoplasm of F-gK beta-infected Vero
      cells, virus particles did not reach the cell surface, and the few enveloped
      particles that were produced exhibited a reduced capacity to enter cells and
      initiate an infection of complementing cells. Overexpression of gK in HSV
      infected cells also caused defects in virus egress, although particles
      accumulated in the perinuclear space and large multilamellar membranous
      structures juxtaposed with the nuclear envelope were observed. Together, these
      results demonstrate that gK regulates or facilitates egress of HSV from cells.
      How this property is connected to cell fusion is not clear. In this regard, gK
      may alter cell surface transport of viral particles or other viral components
      directly involved in the fusion process.

PMID- 7636986
TI  - The B-cell response in lymphoid tissue of mice immunized with various antigenic
      forms of the influenza virus hemagglutinin.
AB  - Protection of BALB/c (H-2d) mice against secondary challenge with influenza A
      viruses is primarily dependent on appropriate recognition of the hemagglutinin
      (HA) molecule by effectors of humoral immunity, the B lymphocytes and their
      product the immunoglobulin molecules. The influence of the antigenic form of the
      HA in eliciting protective antibodies is not clearly defined. We directly
      monitored the kinetics, character, localization, and helper T-cell dependence of
      the primary antibody-forming cell (AFC) response and the development of B-cell
      memory in lymphoid tissues associated with the upper and lower respiratory
      tracts, and in the spleen and bone marrow, to three forms of HA with various
      degrees of antigenic organization. Our results show that the antigenic
      organization of HA substantially influences B-cell immunity, namely, the capacity
      to generate both primary AFCs and memory B cells responsive to lethal challenge.
      Immunization by infection is the most efficient means of generating protective
      memory B cells, in contrast to subunit vaccine. The data also indicate that
      memory AFCs are predominantly localized to the regional lymphoid tissue where
      challenge HA is found, unlike primary AFCs, which are restricted to the priming
      site and which require in vivo CD4+ T-cell help.

PMID- 7636987
TI  - Minute virus of mice transcriptional activator protein NS1 binds directly to the
      transactivation region of the viral P38 promoter in a strictly ATP-dependent
      manner.
AB  - The NS1 polypeptide of minute virus of mice (MVM) is a potent transcriptional
      activator of the MVM P38 promoter. The minimum region of this promoter required
      for transactivation has been identified and termed the transactivation region
      (tar). However, the function of tar and the biochemical steps involved in NS1
      mediated transactivation are not well understood. Here we provide evidence that
      NS1 binds directly and specifically to tar in a strictly ATP-dependent manner. A
      DNA fragment containing tar was specifically coimmunoprecipitated with purified
      baculovirus-expressed MVM NS1, using antibodies directed against NS1 amino- or
      carboxy-terminal peptides. Using this immunoprecipitation assay, we found that
      the NS1-tar interaction was enhanced approximately 10-fold by ATP, but subsequent
      incubation at elevated temperatures in the presence, but not the absence, of
      MgCl2 caused rapid loss of tar binding. This finding suggests that the tar-NS1
      complex has a short half-life under assay conditions which favor ATP hydrolysis.
      Specific binding was efficiently inhibited by self-ligated oligonucleotides
      containing the core DNA sequence (ACCA)3, but the same nonligated 20- and 21-mer
      oligonucleotides were unable to compete effectively, indicating that NS1 only
      binds to its cognate site when this site is presented on DNA fragments of
      sufficient size. DNase I footprinting experiments performed in the presence of
      gamma S-ATP revealed that NS1 protects a 43-bp sequence extending asymmetrically
      from the (ACCA)2 sequence toward the TATA box of the promoter. NS1 footprints
      obtained at other sites in the MVM genome were similarly large and asymmetric,
      all extending approximately 31 bp 5' from the core (ACCA)2-3 sequence.
      Surprisingly, no footprints were obtained in the absence of gamma S-ATP even
      under low-stringency binding conditions. However, ATP could be omitted from the
      reactions if NS1 was first incubated with antibodies directed against its 16
      amino-acid carboxy-terminal peptide. Since these antibodies probably create
      intermolecular cross-links, this finding suggests that NS1 may only bind its
      cognate site efficiently, or perhaps at all, if the transactivator is first
      induced to form oligomers. From these data, we hypothesize that ATP binding may
      also induce NS1 to oligomerize and that such assembly is required before the
      protein can bind effectively to the tar sequence. The functional implications of
      the NS1-tar interaction will be discussed.

PMID- 7636988
TI  - Analysis of resistance to human immunodeficiency virus type 1 protease inhibitors
      by using matched bacterial expression and proviral infection vectors.
AB  - There are already reports, from clinical trials with human immunodeficiency virus
      type 1 protease inhibitors, of the emergence of drug-resistant mutants which have
      one or more point mutations in their protease genes. To examine roles of
      individual and multiple amino acid substitutions in terms of altered enzyme and
      virus drug sensitivities, we have produced matched vectors for bacterial
      expression and virus production. Both vectors accept the same restriction enzyme
      fragment, produced by PCR or PCR-mutagenesis of the protease gene, allowing
      parallel expression of mutant enzymes in Escherichia coli and in recombinant
      viruses. The utility of this vector system was demonstrated by using protease
      variants glycine to valine at amino acid 48 (G48V) and leucine to methionine at
      amino acid 90 (L90M) identified after passage of HIV-1 in the Roche phase II
      clinical trial protease inhibitor Ro 31-8959 (H. Jacobsen, K. Yasargil, D. L.
      Winslow, J. C. Craig, A. Krohn, I. B. Duncan, and J. Mous, Virology 206:527,
      1995). G48V, L90M, and G48V/L90M exhibited successively less processing in vitro
      than the wild-type enzyme, and the purified enzymes were 220-, 20-, and 720-fold,
      respectively, less sensitive to Ro 31-8959. The reduced enzyme sensitivity
      correlated directly with the sensitivities of the matched recombinant viruses, in
      that individual mutations L90M and G48V conferred 2-fold and 4- to 6-fold
      increases in 50% inhibitory concentration, respectively, whereas G48V/L90M was 8
      to 10 times less sensitive to Ro 31-8959. A proviral vector with the entire
      protease gene deleted was constructed for use as an in vivo recombination target
      for an overlapping protease PCR fragment, generating wild-type infectious virus.
      Finally, direct ligation of restriction fragments, generated from random PCR
      mutagenesis, into the proviral vector should provide a library of protease
      mutations that allow extremely rapid selection of highly resistant viral
      variants.

PMID- 7636989
TI  - A novel method for efficient amplification of whole hepatitis B virus genomes
      permits rapid functional analysis and reveals deletion mutants in
      immunosuppressed patients.
AB  - Current knowledge of hepatitis B virus (HBV) sequence heterogeneity is based
      mainly on sequencing of amplified subgenomic HBV fragments. Here, we describe a
      method which allows sensitive amplification and simplified functional analysis of
      full-length HBV genomes with or without prior cloning. By this method, a large
      number of HBV genomes were cloned from sera of six immunosuppressed kidney
      transplant patients. Two size classes of HBV genomes, one 3.2 kb and another
      about 2.0 kb in size, were found in all patients. The genome population from one
      serum sample was studied in detail by size analysis of subgenomic PCR fragments
      and sequencing. Regions with deletions and insertions were mapped in the C gene
      and pre-S region. Up to 100% of HBV genomes in all other immunosuppressed
      patients also had deletions in the C gene. Our results demonstrate the potential
      of the established method for the structural and functional characterization of
      heterogeneous populations of complete virion-encapsidated HBV DNAs and suggest
      that HBV genomes with C gene deletions can have a selective advantage in
      immunosuppressed patients.

PMID- 7636990
TI  - The caprine arthritis encephalitis virus tat gene is dispensable for efficient
      viral replication in vitro and in vivo.
AB  - Caprine arthritis encephalitis virus (CAEV) is a lentivirus closely related to
      visna virus and more distantly to other lentiviruses, such as human
      immunodeficiency virus. The genomes of visna virus and CAEV contain a tat gene
      encoding a protein able to weakly transactivate its own long terminal repeat,
      suggesting that transactivation may be a dispensable function for viral
      replication. Three different tat gene mutants of an infectious molecular clone of
      CAEV were used to study their replication after transfection or infection of
      primary goat synovial membrane cells and of blood-derived mononuclear cells or
      macrophages. Our results showed no difference between replication of the wild
      type and either the complete tat deletion mutant or the tat stop point mutant,
      whereas slower growth kinetics and lower levels of expression of the partial tat
      deletion mutant that of the wild type were obtained in these cells. Quantitative
      PCR and reverse transcription-PCR analyses of the different steps of a single
      replicative cycle revealed an identical pattern of retrotranscription,
      transcription, and viral production, whereas time course analysis demonstrated
      that the intracellular level of viral genomic RNA was affected by the partial tat
      deletion at later time points. We then compared the infectious properties of the
      wild-type and tat mutant viruses in vivo by direct inoculation of proviral DNAs
      into the joints of goats. All the animals seroconverted between 27 and 70 days
      postinoculation. Moreover, we were able to isolate tat mutant CAEV from blood
      derived macrophages that was still able to infect synovial membrane cells in
      vitro. This study clearly demonstrates that the tat gene of CAEV is dispensable
      for viral replication in vitro and in vivo.

PMID- 7636991
TI  - Positionally independent and exchangeable late budding functions of the Rous
      sarcoma virus and human immunodeficiency virus Gag proteins.
AB  - The Gag proteins of Rous sarcoma virus and human immunodeficiency virus (HIV)
      each contain a function involved in a late step in budding, defects in which
      result in the accumulation of these molecules at the plasma membrane. In the Rous
      sarcoma virus Gag protein (Pr76gag), this assembly domain is associated with a
      PPPY motif, which is located at an internal position between the MA and CA
      sequences. This motif is not contained anywhere within the HIV Gag protein
      (Pr55gag), and the MA sequence is linked directly to CA. Instead, a late assembly
      function of HIV has been associated with the p6 sequence situated at the C
      terminus of Gag. Here we demonstrate the remarkable finding that the late
      assembly domains from these two unrelated Gag proteins are exchangeable between
      retroviruses and can function in a positionally independent manner.

PMID- 7636992
TI  - Gamma interferon is a major mediator of antiviral defense in experimental measles
      virus-induced encephalitis.
AB  - Measles virus infection of the central nervous system in the murine model of
      experimental measles virus-induced encephalitis is successfully controlled by
      virus-specific T-helper lymphocytes. T cells from BALB/c mice that are resistant
      to measles virus encephalitis proliferate well against measles virus in vitro,
      and bulk cultures recognize viral nucleocapsid and hemagglutinin as well as
      fusion proteins. The measles virus-specific T cells secrete large amounts of
      interleukin 2 (IL-2), gamma interferon (IFN-gamma), and tumor necrosis factor
      alpha (TNF-alpha) but no IL-4, IL-6, or IL-10, and hence the cytokine pattern is
      consistent with that of subtype 1 T-helper lymphocytes. In contrast, cells
      obtained from measles virus-infected susceptible C3H mice recognize measles virus
      proteins only weakly and secrete little IFN-gamma and TNF-alpha. Treatment of
      infected mice with anti-TNF-alpha antibodies has no effect on survival or virus
      clearance from the brain. Upon neutralization of IFN-gamma in vivo, the phenotype
      of measles virus-specific T-helper cells isolatable from BALB/c mice is reversed
      from subtype 1 to subtype 2-like. Anti-IFN-gamma antibody-treated BALB/c mice are
      susceptible to measles virus encephalitis, and viral clearance from the central
      nervous system is impaired. These results indicate that IFN-gamma plays a
      significant role in the control of measles virus infection of the central nervous
      system.

PMID- 7636993
TI  - Construction of murine coronavirus mutants containing interspecies chimeric
      nucleocapsid proteins.
AB  - Targeted RNA recombination was used to construct mouse hepatitis virus (MHV)
      mutants containing chimeric nucleocapsid (N) protein genes in which segments of
      the bovine coronavirus N gene were substituted in place of their corresponding
      MHV sequences. This defined portions of the two N proteins that, despite
      evolutionary divergence, have remained functionally equivalent. These regions
      included most of the centrally located RNA-binding domain and two putative
      spacers that link the three domains of the N protein. By contrast, the amino
      terminus of N, the acidic carboxy-terminal domain, and a serine- and arginine
      rich segment of the central domain could not be transferred from bovine
      coronavirus to MHV, presumably because these parts of the molecule participate in
      protein-protein interactions that are specific for each virus (or, possibly, each
      host). Our results demonstrate that targeted recombination can be used to make
      extensive substitutions in the coronavirus genome and can generate recombinants
      that could not otherwise be made between two viruses separated by a species
      barrier. The implications of these findings for N protein structure and function
      as well as for coronavirus RNA recombination are discussed.

PMID- 7636994
TI  - Mutational analysis of adeno-associated virus Rep protein-mediated inhibition of
      heterologous and homologous promoters.
AB  - The four Rep proteins encoded by adeno-associated virus type 2 (AAV-2) inhibit
      transcription of their own promoters and of several heterologous promoters. To
      gain insight into the molecular mechanism of Rep-mediated transcription
      repression, we studied the effects of the four Rep proteins on the accumulation
      of mRNA transcribed from the human papillomavirus type 18 upstream regulatory
      region HPV18 URR, the human immunodeficiency virus long terminal repeat, and the
      AAV-2 p5 and p19 promoters by transient transfection experiments in HeLa cells.
      We observed a distinct contribution of the C- and N-terminal sequences in which
      the four Rep proteins (Rep78, Rep68, Rep52, and Rep40) differ from each other.
      While Rep78 showed a more than 10-fold inhibition of the four promoters studied,
      transcriptional repression mediated by Rep68 and Rep52 was reduced and nearly
      completely abolished for Rep40. The contribution of the C terminus of Rep78 was
      reduced with respect to the inhibition of the AAV-2 p5 and p19 promoters. Point
      mutations and deletions showed that a C-terminal zinc binding motif is required
      for zinc binding in vitro but plays no obvious role in the inhibition of
      homologous and heterologous promoters. Overall, inhibition of the four different
      promoters was dependent on the identical Rep protein domains with the exception
      of the AAV-2 p5 promoter. Expression of the AAV-2 p5 promoter was inhibited by a
      Rep78 protein with a mutation in the nucleotide binding motif, whereas expression
      of the AAV-2 p19 promoter, the human immunodeficiency virus long terminal repeat,
      and the HPV18 URR was not. Mutational analysis of the HPV18 URR showed that
      several, but not a single, cis regulatory elements are involved in the inhibition
      process. This finding suggests that transcriptional repression is mediated by
      protein-protein interactions of the Rep proteins either with multiple
      transcription factors or with target proteins of sequence-specific transcription
      factors of the basal transcription machinery.

PMID- 7636995
TI  - Interference with bacteriophage phi 6 genomic RNA packaging by hairpin
      structures.
AB  - Bacteriophage phi 6 has a genome of three segments of double-stranded RNA
      enclosed in a procapsid composed of four different proteins. The preformed
      procapsid is capable of packaging plus-strand transcripts of the genomic segments
      in an in vitro reaction. Minus-strand synthesis within the procapsid then results
      in the production of the double-stranded RNA genome. When plus-strand transcripts
      contain strong hairpin structures near the 3' ends, they are subject to
      heterologous recombination to remove the hairpins. We now find that the sequences
      bounded by the hairpins as well as those 3' to them are excluded from particles
      in packaging reactions. This finding implies that packaging occurs from the 5'
      end and that the explanation for the facilitation of recombination by the hairpin
      structures is the lack of entry of the 3' ends rather than a difficulty of
      progressing through the hairpin by the phage polymerase. Packaging of segment M
      is dependent on the packaging of segment S. An S segment containing a strong
      hairpin is able to facilitate the packaging of segment M. This result implies
      that there is more than one entry pore into the procapsid.

PMID- 7636996
TI  - Upstream CREs participate in the basal activity of minute virus of mice promoter
      P4 and in its stimulation in ras-transformed cells.
AB  - The activity of the P4 promoter of the parvovirus minute virus of mice (prototype
      strain MVMp) is stimulated in ras-transformed FREJ4 cells compared with the
      parental FR3T3 line. This activation may participate in the oncolytic effect of
      parvoviruses, given that P4 drives a transcriptional unit encoding cytotoxic
      nonstructural proteins. Our results suggest that the higher transcriptional
      activity of promoter P4 in FREJ4 cells is mediated at least in part by upstream
      CRE elements. Accordingly, mutations in the CRE motifs impair P4 function more
      strongly in the FREJ4 derivative than in its FR3T3 parent. Further evidence that
      these elements contribute to hyperactivity of the P4 promoter in the ras
      transformant is the fact that they form distinct complexes with proteins from
      FREJ4 and FR3T3 cell extracts. This difference can be abolished by treating the
      FREJ4 cell extracts with cyclic AMP-dependent protein kinase (PKA) or treating
      original cultures with a PKA activator. These findings can be linked with two
      previously reported features of ras-transformed cells: the activation of a PKA
      inhibited protein kinase cascade and the reduction of PKA-induced protein
      phosphorylation. In keeping with these facts, P4-directed gene expression can be
      up- or downmodulated in vivo by exposing cells to known inhibitors or activators
      of PKA, respectively.

PMID- 7636997
TI  - Complete replication of poliovirus in vitro: preinitiation RNA replication
      complexes require soluble cellular factors for the synthesis of VPg-linked RNA.
AB  - Translation of poliovirion RNA in HeLa S10 extracts resulted in the formation of
      RNA replication complexes which catalyzed the asymmetric replication of
      poliovirus RNA. Synthesis of poliovirus RNA was detected in unfractionated HeLa
      S10 translation reactions and in RNA replication complexes isolated from HeLa S10
      translation reactions by pulse-labeling with [32P]CTP. The RNA replication
      complexes formed in vitro contained replicative-intermediate RNA and were
      enriched in viral protein 3CD and the membrane-associated viral proteins 2C, 2BC,
      and 3AB. Genome-length poliovirus RNA covalently linked to VPg was synthesized in
      large amounts by the replication complexes. RNA replication was highly
      asymmetric, with predominantly positive-polarity RNA products. Both anti-VPg
      antibody and guanidine HCl inhibited RNA replication and virus formation in the
      HeLa S10 translation reactions without affecting viral protein synthesis. The
      inhibition of RNA synthesis by guanidine was reversible. The reversible nature of
      guanidine inhibition was used to demonstrate the formation of preinitiation RNA
      replication complexes in reaction mixes containing 2 mM guanidine HCl.
      Preinitiation complexes sedimented upon centrifugation at 15,000 x g and
      initiated RNA replication upon their resuspension in reaction mixes lacking
      guanidine. Initiation of RNA synthesis by preinitiation complexes did not require
      active protein synthesis or the addition of soluble viral proteins. Initiation of
      RNA synthesis by preinitiation complexes, however, was absolutely dependent on
      soluble HeLa cytoplasmic factors. Preinitiation complexes also catalyzed the
      formation of infectious virus in reaction mixes containing exogenously added
      capsid proteins. The titer of infectious virus produced in such trans
      encapsidation reactions reached 4 x 10(7) PFU/ml. The HeLa S10 translation-RNA
      replication reactions represent an efficient in vitro system for authentic
      poliovirus replication, including protein synthesis, polyprotein processing, RNA
      replication, and virus assembly.

PMID- 7636998
TI  - Persistent infection of cultured cells with mouse hepatitis virus (MHV) results
      from the epigenetic expression of the MHV receptor.
AB  - The A59 strain of murine coronavirus mouse hepatitis virus (MHV) can cause
      persistent infection of 17C1-1 cells and other murine cell lines. Persistently
      infected cultures released large amounts of virus (10(7) to 10(8) PFU/ml) and
      were resistant to superinfection with MHV but not to infection with unrelated
      Semliki Forest and vesicular stomatitis viruses. The culture medium from
      persistently infected cultures did not contain a soluble inhibitor such as
      interferon that protected uninfected cells from infection by MHV or vesicular
      stomatitis virus. The persistent infection was cured if fewer than 100 cells were
      transferred during subculturing, and such cured cultures were susceptible to
      reinfection and the reestablishment of persistent infection. Cultures of 17C1-1
      cells that had been newly cloned from single cells consisted of a mixture of MHV
      resistant and -susceptible cells. 17C1-1/#97 cells, which were cured by
      subcloning after 97 passages of a persistently infected culture over a 1-year
      period, contained 5 to 10% of their population as susceptible cells, while 17C1
      1/#402 cells, which were cured by subcloning after 402 passages over a 3-year
      period, had less than 1% susceptible cells. Susceptibility to infection
      correlated with the expression of MHV receptor glycoprotein (MHVR [Bgp1a]).
      Fluorescence-activated cell sorter analysis with antibody to MHVR showed that
      17C1-1/#97 cells contained a small fraction of MHVR-expressing cells. These MHVR
      expressing cells were selectively eliminated within 24 h after challenge with MHV
      A59, and pretreatment of 17C1-1/#97 cells with monoclonal antibody CC1, which
      binds to the N-terminal domain of MHVR, blocked infection. We conclude that the
      subpopulation of MHVR-expressing cells were infected and killed in acutely or
      persistently infected cultures, while the subpopulation of MHVR-nonexpressing
      cells survived and proliferated. The subpopulation of MHVR-negative cells
      produced a small proportion of progeny cells that expressed MHVR and became
      infected, thereby maintaining the persistent infection as a steady-state carrier
      culture. Thus, in 17C1-1 cell cultures, the unstable or epigenetic expression of
      MHVR permitted the establishment of a persistent, chronic infection.

PMID- 7636999
TI  - The leader polypeptide of Theiler's virus is essential for neurovirulence but not
      for virus growth in BHK cells.
AB  - A leader polypeptide of unknown function is encoded by cardioviruses, such as
      Theiler's murine encephalomyelitis virus. Although the deletion of this
      polypeptide has little effect on the growth of parental GDVII virus in baby
      hamster kidney (BHK) cells, the mutant virus is completely attenuated and fails
      to kill mice receiving intracerebral inoculations of high doses of the virus.

PMID- 7637000
TI  - Herpes simplex virus immediate-early protein ICP22 is required for viral
      modification of host RNA polymerase II and establishment of the normal viral
      transcription program.
AB  - Infection of cells with herpes simplex virus type 1 (HSV-1) results in a rapid
      alteration of phosphorylation on the large subunit of cellular RNA polymerase II
      (RNAP II), most likely on its C-terminal domain (S. A. Rice, M. C. Long, V. Lam,
      C. A. Spencer, J. Virol. 68:988-1001, 1994). This phosphorylation modification
      generates a novel form of the large subunit which we have designed IIi. In this
      study, we examine roles that HSV-1 gene products play in this process. An HSV-1
      mutant defective in the immediate-early transcriptional activator protein ICP4 is
      able to efficiently induce IIi. Viruses having mutations in the genes for the
      ICP0, ICP6, or ICP27 proteins are also competent for IIi formation. In contrast,
      22/n199, an HSV-1 mutant which contains a nonsense mutation in the gene encoding
      the immediate-early protein ICP22, is significantly deficient in IIi induction.
      This effect is seen in Vero cells, where 22/n199 grows relatively efficiently,
      and in human embryonic lung (HEL) cells, where 22/n199 growth in more restricted.
      RNAP II is recruited into viral replication compartments in 22/n199-infected
      cells, indicating that altered phosphorylation of RNAP II is not a prerequisite
      for nuclear relocalization of RNAP II. In addition, we show by nuclear run-on
      transcription analysis that viral gene transcription is deficient in HEL cells
      infected with 22/n199. Viral late gene transcription does not occur efficiently,
      and antisense transcription throughout the genome is diminished compared with
      that of the wild-type HSV-1 infection. These transcriptional effects cannot be
      explained by differences in viral DNA replication, since 22/n199 replicates its
      DNA efficiently in HEL cells. Our results demonstrated that ICP22 is necessary
      for virus-induced aberrant phosphorylation of RNAP II and for normal patterns of
      viral gene transcription in certain cell lines.

PMID- 7637003
TI  - Hepatitis A viruses with deletions in the 2A gene are infectious in cultured
      cells and marmosets.
AB  - The 2A gene of hepatitis A virus (HAV) bears no obvious similarity to the
      corresponding genes of other picornaviruses and has no known function. In a
      preliminary effort to gain information about the HAV 2A gene product, we
      constructed several HAV cDNAs containing deletions of 30 or 45 nucleotides in the
      predicted central portion of the 2A gene. These deletions did not affect the
      sites of protein processing, although the rates or efficiencies of polyprotein
      cleavage at the surrounding cleavage junctions appeared slightly reduced.
      Transfection of FRhK-4 cells with RNA transcripts of the deleted HAV cDNAs
      generated small foci of infected cells and produced infectious virus that
      retained the deletion mutations. In contrast, a single amino acid insertion in
      the 2B coding region was lethal to virus replication despite normal protein
      processing. Another deletion, which included the predicted 2A/2B junction and
      extended into the 2B coding sequence, did not support polyprotein processing or
      generate viable virus. One of the viable internal 2A deletions was introduced
      into a wild-type HAV cDNA background, and transcripts were tested for infectivity
      by inoculation directly into the livers of two marmosets. Both animals
      seroconverted, displayed elevated serum liver enzymes, and excreted infectious
      virus. Thus, deletion of 10 or 15 amino acid residues from the predicted central
      portion of the 2A protein was tolerated with only relatively minor effects on the
      growth of HAV in cultured cells and in marmoset liver.

PMID- 7637001
TI  - Pseudorabies virus and equine herpesvirus 1 share a nonessential gene which is
      absent in other herpesviruses and located adjacent to a highly conserved gene
      cluster.
AB  - We have determined the nucleotide sequence and transcriptional pattern of a group
      of open reading frames in the pseudorabies virus (PrV) genome located near the
      left end of the unique long region within BamHI 5' fragment at map positions 0.01
      to 0.06. The 7,412-bp BamHI 5' fragment was found to contain five complete open
      reading frames and part of a sixth whose deduced amino acid sequences showed
      homology to the UL50 (partial), UL51, UL52, UL53, and UL54 gene products of
      herpes simplex virus type 1 (HSV-1) and corresponding genes identified in other
      alphaherpesviruses. Homologs to the UL55 and UL56 genes of HSV-1 were not
      detected. However, we identified a gene with homology only to the first open
      reading frame (ORF-1) of the equine herpesvirus 1 strain Ab4 (E. A. Telford, M.
      S. Watson, K. McBride, and A. J. Davison, Virology 189:304-316, 1992). Northern
      blot analyses revealed unique mRNAs for the UL51, UL54, and ORF-1 genes and a set
      of 3'-coterminal mRNAs for the UL52 to UL54 genes. A PrV mutant lacking ORF-1 was
      isolated after deletion of ORF-1 coding sequences and insertion of a lacZ
      expression cassette. The ORF-1- PrV mutant was able to productively replicate in
      noncomplementing cells to levels similar to those of wild-type PrV, proving that
      ORF-1 is not essential for replication of PrV in cell culture. The conservation
      of this gene between PrV and equine herpesvirus 1 documents the close
      evolutionary relationship between these animal herpesviruses and points to a
      possible function of the respective proteins in infection of the natural host.

PMID- 7637002
TI  - Relationship between TATA-binding protein and herpes simplex virus type 1 ICP4
      DNA-binding sites in complex formation and repression of transcription.
AB  - The herpes simplex virus (HSV) regulatory protein, infected-cell polypeptide 4
      (ICP4), represses the transcription of promoters that have binding sites for ICP4
      located near the transcription start site. It also been shown that ICP4 binds
      such promoter DNA cooperatively with the TATA-binding protein (TBP) and TFIIB to
      form a tripartite protein-DNA complex (C. Smith, P. Bates, R. Rivera-Gonzales, B.
      Gu, and N. A. DeLuca, J. Virol. 67:4676-4687, 1993). In this study, we analyzed
      the effects of position and orientation of the ICP4-binding site relative to the
      TATA box in the ICP4 promoter on transcriptional repression by ICP4 and on the
      ability of ICP4 to form tripartite complexes with TBP and TFIIB. The results of
      theis parallel study provide a strong correlation between tripartite complex
      formation and repression. Both tripartite-complex formation and transcriptional
      repression were efficient when the ICP4-binding site was downstream of the TATA
      box, within a short distance and in proper orientation. In addition, both
      tripartite-complex formation and repression were partially sensitive to the
      stereoaxial positioning of the ICP4-binding site relative to the TATA box. As a
      preliminary characterization of the tripartite complex, circular permutation
      analysis was performed to assess the distortion of the proximal promoter region
      in the tripartite complex. As previously reported, both TBP and ICP4
      independently could bend DNA and the relative magnitude by which each of these
      proteins bent DNA in the tripartite complex was preserved. The results of this
      study suggest that the formation of tripartite complexes on a promoter is part of
      the mechanism of repression and that simple blocking as a sole result of ICP4
      binding is not sufficient for full repression.

PMID- 7637004
TI  - Rotavirus-induced fusion from without in tissue culture cells.
AB  - We present the first evidence of fusion from without induced in tissue culture
      cells by a nonenveloped virus. Electron micrographs of two strains of rotavirus,
      bovine rotavirus C486 and rhesus rotavirus, show that virally mediated cell-cell
      fusion occurs within 1 h postinfection. Trypsin activation is necessary for
      rotavirus to mediate cell-cell fusion. The extent of fusion is relative to the
      amount of virus used, and maximum fusion occurs between pHs 6.5 and 7.5. Fusion
      does not require virus-induced protein synthesis, as virus from both an empty
      capsid preparation and from an EDTA-treated preparation, which is noninfectious,
      can induce fusion. Incubation of rotavirus with neutralizing and nonneutralizing
      monoclonal antibodies before addition to cells indicates that viral protein 4
      (VP4; in the form of VP5* and VP8*) and VP7 are involved in fusion. Light and
      electron micrographs document this fusion, including the formation of pores or
      channels between adjacent fused cells. These data support direct membrane
      penetration as a possible route of infection. Moreover, the assay should be
      useful in determining the mechanisms of cell entry by rotavirus.

PMID- 7637006
TI  - The neurovirulent GDVII strain of Theiler's virus can replicate in glial cells.
AB  - The distribution, spread, neuropathology, tropism, and persistence of the
      neurovirulent GDVII strain of Theiler's virus in the central nervous system (CNS)
      was investigated in mice susceptible and resistant to chronic demyelinating
      infection with TO strains. Following intracerebral inoculation, the virus spread
      rapidly to specific areas of the CNS. There were, however, specific structures in
      which infection was consistently undetectable. Virus spread both between adjacent
      cell bodies and along neuronal pathways. The distribution of the infection was
      dependent on the site of inoculation. The majority of viral RNA-positive cells
      were neurons. Many astrocytes were also positive. Infection of both of these cell
      types was lytic. In contrast, viral RNA-positive oligodendrocytes were rare and
      were observed only in well-established areas of infection. The majority of
      oligodendrocytes in these areas were viral RNA negative and were often the major
      cell type remaining; however, occasional destruction of these cells was observed.
      No differences in any of the above parameters were observed between CBA and
      BALB/c mice, susceptible and resistant, respectively, to chronic CNS
      demyelinating infection with TO strains of Theiler's virus. By using Southern
      blot hybridization to detect reverse-transcribed PCR-amplified viral RNA
      sequences, no virus persistence could be detected in the CNS of immunized mice
      surviving infection with GDVII. In conclusion, the GDVII strain of Theiler's
      murine encephalomyelitis virus cannot persist in the CNS, but this is not
      consequent upon an inability to infect glial cells, including oligodendrocytes.

PMID- 7637005
TI  - Differential antigen burden modulates the gamma interferon but not the
      immunoglobulin response in mice that vary in susceptibility to Sendai virus
      pneumonia.
AB  - Sendai virus, a paramyxovirus which causes murine pneumonia, grew to
      approximately 10-fold higher titers and was cleared less rapidly from the lungs
      of 129/J (129) than H-2b-compatible C57BL/6J (B6) mice. The more susceptible 129
      mice also made higher titers of gamma interferon (IFN-gamma) and immunoglobulin
      G2a (IgG2a) virus-specific antibody. Analysis with acutely irradiated (950 rads)
      mice and immunologically reconstituted bone marrow (BM) radiation chimeras
      indicated that the enhanced virus growth was a function of the radiation
      resistant respiratory epithelium. Prolonged exposure to more virus in turn
      influenced the magnitude of IFN-gamma production, most of which was made by CD4+
      T lymphocytes. Somewhat surprisingly, however, the 129 pattern of a higher virus
      specific serum Ig response skewed towards IgG2a mapped to the reconstituting BM.
      Thus, the characteristics of the humoral response are at least partly dissociated
      from both the antigen load, resulting from viral replication, and the level of
      IFN-gamma production. Further analysis of double chimeras (B6+129 BM-->B6
      recipients) confirmed that the divergent humoral immune response to Sendai virus
      in B6 and 129 mice is largely determined by the inherent characteristics of the
      lymphoid cells.

PMID- 7637007
TI  - Efficient expression of the human papillomavirus type 16 L1 protein in epithelial
      cells by using Rev and the Rev-responsive element of human immunodeficiency virus
      or the cis-acting transactivation element of simian retrovirus type 1.
AB  - Production of the human papillomavirus (HPV) late gene products L1 and L2 is
      limited to terminally differentiated keratinocytes. Here, we demonstrate that
      mRNA encoding the HPV-16 L1 capsid protein contains cis-acting RNA elements that
      inhibit expression at the posttranscriptional level. While cytoplasmic L1 mRNA is
      detectable in transfected HeLa cells, L1 protein is not produced. We have
      identified at least one major inhibitory element that is located within the L1
      open reading frame, whereas another negative element had been reported to lie in
      the 3'-untranslated region of L1. The presence of these elements may explain the
      lack of HPV late gene expression in undifferentiated epithelial cells. Efficient
      production of HPV-16 L1 could be achieved with posttranscriptional regulatory
      elements of human immunodeficiency virus type 1 or simian retrovirus type 1. L1
      protein was expressed in the presence of human immunodeficiency virus type 1 Rev
      from hybrid mRNAs containing the RNA binding site for Rev (Rev-responsive
      element). In addition, we have achieved efficient expression of L1 from hybrid
      mRNAs containing a cis-acting transactivation element from simian retrovirus type
      1. Our data show that HPV-16 L1 protein production is regulated
      posttranscriptionally. This regulated expression may allow virus production in
      terminally differentiated epithelial cells and is probably a conserved and
      important mechanism for HPV expression.

PMID- 7637008
TI  - Genomic organization of GB viruses A and B: two new members of the Flaviviridae
      associated with GB agent hepatitis.
AB  - The genomes of two positive-strand RNA viruses have recently been cloned from the
      serum of a GB agent-infected tamarin by using representational difference
      analysis. The two agent, GB viruses A and B (GBV-A and GBV-B, respectively), have
      genomes of 9,493 and 9,143 nucleotides, respectively, and single large open
      reading frames that encode potential polyprotein precursors of 2,972 and 2,864
      amino acids, respectively. The genomes of these agents are organized much like
      those of other pestiviruses and flaviviruses, with genes predicted to encode
      structural and nonstructural proteins located at the 5' and 3' ends,
      respectively. Amino acid sequence alignments and subsequent phylogenetic analysis
      of the RNA-dependent RNA polymerases (RdRps) of GBV-A and GBV-B show that they
      possess conserved sequence motifs associated with supergroup II RNA polymerases
      of positive-strand RNA viruses. On the basis of similar analyses, the GBV-A- and
      GBV-B-encoded helicases show significant identity with the supergroup II
      helicases of positive-strand RNA viruses. Within the supergroup II RNA
      polymerases and helicases, GBV-A and GBV-B are most closely related to the
      hepatitis C virus group. Across their entire open reading frames, the GB agents
      exhibit 27% amino sequence identity to each other, approximately 28% identity to
      hepatitis C virus type 1, and approximately 20% identity to either bovine viral
      diarrhea virus or yellow fever virus. The degree of sequence divergence between
      GBV-A and GBV-B and other Flaviviridae members demonstrates that the GB agents
      are representatives of two new genera within the Flaviviridae family.

PMID- 7637009
TI  - Monoclonal antibodies against Rous sarcoma virus integrase protein exert
      differential effects on integrase function in vitro.
AB  - We have prepared and characterized several monoclonal antibodies (MAbs) against
      the Rous sarcoma virus integrase protein (IN) with the aim of employing these
      specific reagents as tools for biochemical and biophysical studies. The
      interaction of IN with the purified MAbs and their Fab fragment derivatives was
      demonstrated by Western blot (immunoblot), enzyme-linked immunosorbent assay, and
      size exclusion chromatography. A series of truncated IN proteins was used to
      determine regions in the protein important for recognition by the antibodies. The
      MAbs described here recognize epitopes that lie within the catalytic core region
      of IN (amino acids 50 to 207) and are likely to be conformational. A detailed
      functional analysis was carried out by investigating the effects of Fab fragments
      as well as of intact MAbs on the activities of IN in vitro. These studies
      revealed differential effects which fall into three categories. (i) One of the
      antibodies completely neutralized the processing as well as the joining activity
      and also reduced the DNA binding capacity as determined by a nitrocellulose
      filter binding assay. On the other hand, this MAb did not abolish the cleavage
      ligation reaction on a disintegration substrate and the nonspecific cleavage of
      DNA by IN. The cleavage pattern generated by the IN-MAb complex on various DNA
      substrates closely resembled that produced by mutant IN proteins which show a
      deficiency in multimerization. Preincubation of IN with substrate protected the
      enzyme from inhibition by this antibody. (ii) Two other antibodies showed a
      general inhibition of all IN activities tested. (iii) In contrast, a fourth MAb
      stimulated the in vitro joining activity of IN. Size exclusion chromatography
      demonstrated that IN-Fab complexes from representatives of the three categories
      of MAbs exhibit different stoichiometric compositions that suggest possible
      explanations for their contrasting effects and may provide clues to the
      relationship between the structure and function of IN.

PMID- 7637010
TI  - Variability of human immunodeficiency virus type 1 group O strains isolated from
      Cameroonian patients living in France.
AB  - Human immunodeficiency virus type 1 (HIV-1) nucleotide sequences encoding p24Gag
      and the Env C2V3 region were obtained from seven patients who were selected on
      the basis of having paradoxical seronegativity on a subset of HIV enzyme-linked
      immunosorbent assay detection kits and having atypical Western blot (immunoblot)
      reactivity. Sequence analyses showed that all of these strains were more closely
      related to the recently described Cameroonian HIV isolates of group O (HIV-1
      outlier) than to group M (HIV-1 major). All seven patients had Cameroonian
      origins but were living in France at the time the blood samples were taken.
      Characterization of a large number of group M strains has to date revealed eight
      distinct genetic subtypes (A to H). Genetic distances between sequences from
      available group O isolates were generally comparable to those observed in M
      intersubtype sequence comparisons, showing that the group O viruses are
      genetically very diverse. Analysis of sequences from these seven new viral
      strains, combined with the three previously characterized group O strains,
      revealed few discernable phylogenetic clustering patterns among the 10 patients'
      viral sequences. The level of diversity among group O sequences suggests that
      they may have a comparable (or greater) age than the M group sequences, although
      for unknown reasons, the latter group dispersed first and is the dominant lineage
      in the pandemic.

PMID- 7637011
TI  - BHK cell proteins that bind to the 3' stem-loop structure of the West Nile virus
      genome RNA.
AB  - The first 83 3' nucleotides of the genome RNA of the flavivirus West Nile
      encephalitis virus (WNV) form a stable stem-loop (SL) structure which is followed
      in the genome by a smaller SL. These 3' structures are highly conserved among
      divergent flaviviruses, suggesting that they may function as cis-acting signals
      for RNA replication and as such might specifically bind to cellular or viral
      proteins. Cellular proteins from uninfected and WNV-infected BHK-21 S100
      cytoplasmic extracts formed three distinct complexes with the WNV plus-strand 3'
      SL [(+)3'SL] RNA in a gel mobility shift assay. Subsequent competitor gel shift
      analyses showed that two of these RNA-protein complexes, complexes 1 and 2,
      contained cell proteins that specifically bound to the WNV (+)3'SL RNA. UV
      induced cross-linking and Northwestern blotting analyses detected WNV (+)3'SL RNA
      binding proteins of 56, 84, and 105 kDa. When the S100 cytoplasmic extracts were
      partially purified by ion-exchange chromatography, a complex that comigrated with
      complex 1 was detected in fraction 19, while a complex that comigrated with
      complex 2 was detected in fraction 17. UV-induced cross-linking experiments
      indicated that an 84-kDa cell protein in fraction 17 and a 105-kDa protein in
      fraction 19 bound specifically to the WNV (+)3'SL RNA. In addition to binding to
      the (+)3'SL RNA, the 105-kDa protein bound to the SL structure located at the 3'
      end of the WNV minus-strand RNA. Initial mapping studies indicated that the 84-
      and 105-kDa proteins bind to different regions of the (+)3'SL RNA. The 3'
      terminal SL RNA of another flavivirus, dengue virus type 3, specifically competed
      with the WNV (+)3'SL RNA in gel shift assays, suggesting that the host proteins
      identified in this study are flavivirus specific.

PMID- 7637012
TI  - Highly purified quiescent human peripheral blood CD4+ T cells are infectible by
      human immunodeficiency virus but do not release virus after activation.
AB  - Previous studies have suggested that resting CD4+ lymphocytes can be infected by
      human immunodeficiency virus (HIV), but viral production is inhibited. If these
      cells are activated, progeny virions are released. The present data indicate that
      CD4+ lymphocytes in the G0/G1 stage of the cell cycle which have been highly
      purified to remove macrophages and activated HLA-DR+ cells can also be infected
      by HIV. However, our findings differ from those of earlier reports since in this
      study, infected quiescent CD4+ cells cannot be activated to produce virus after
      virus inoculation. PCR analyses indicate that reverse transcription in these CD4+
      cells is arrested at a very early step in proviral DNA formation (U3-R region).
      They do not show any evidence of longer DNA transcripts (e.g., U3-gag). When
      these quiescent infected CD4+ lymphocytes are activated by exposure to mitogens
      and macrophages and then reinoculated with HIV, the replication of virus takes
      place. Resting CD4+ lymphocytes are also resistant to infection when they are
      cocultured with HIV-infected macrophages. Only activated CD4+ cells are
      susceptible to cell-to-cell transmission. These observations suggest that in vivo
      tissue macrophages, susceptible to HIV replication, are the major cells initially
      productively infected by the virus. Then these cells can transfer HIV to
      activated CD4+ lymphocytes with resultant virus production. The presence of
      arrested reverse transcription in quiescent cells raises questions about the
      cellular factors required to permit production of longer HIV proviral DNA copies.
      Because they can be reinfected once they have been activated, these infected
      quiescent cells could be a source of recombinant viruses in the host.

PMID- 7637013
TI  - Cytotoxic T cells are elicited during acute infection of mice with lactate
      dehydrogenase-elevating virus but disappear during the chronic phase of
      infection.
AB  - Lactate dehydrogenase-elevating virus (LDV) invariably establishes a life-long
      viremic infection in mice, which is maintained by replication of LDV in a
      renewable subpopulation of macrophages and escape from all host immune responses.
      We now demonstrate that cytotoxic T lymphocytes (CTLs) that specifically lyse LDV
      infected macrophages and 3T3 cells producing the nucleocapsid protein of LDV were
      elicited in Swiss, B10.A, and (Swiss x B10.A)F1 mice. To detect target cell
      lysis, splenocytes needed to be expanded by a 5-day in vitro culture in the
      presence of recombinant interleukin 2 and syngeneic LDV protein-expressing cells.
      In vitro culture resulted in the specific expansion of CD8+ cells which mediated
      the lysis of target cells in a major histocompatibility complex class I
      restricted manner. When CTLs were added to macrophage cultures at 1 h after
      infection with LDV, the lysis of the infected macrophages by the CTLs started
      about 5 h postinfection (p.i.) and, at an effector cell/target cell ratio of
      25:1, resulted in the lysis of all LDV-infected macrophages in a culture by about
      7 h p.i. However, lysis of the LDV replication in a culture was not rapid enough
      to significantly suppress the LDV yield in the culture. LDV replication in mice
      was also little affected by the presence of CTLs which were induced by
      immunization with 3T3 cells expressing the LDV nucleocapsid protein. Furthermore,
      all CTL precursor cells in infected mice had disappeared by 30 days p.i. Loss of
      CTL precursor cells in infected mice probably reflected high-dose clonal
      exhaustion, since LDV infection of a mouse results in massive production of LDV
      in all tissues of the mouse, but especially in lymphoidal tissues, and
      accumulation of LDV in newly formed germinal centers. Furthermore, slow LDV
      replication continues in the thymus and other lymphoidal organs.

PMID- 7637014
TI  - RNA replication by respiratory syncytial virus (RSV) is directed by the N, P, and
      L proteins; transcription also occurs under these conditions but requires RSV
      superinfection for efficient synthesis of full-length mRNA.
AB  - Previously, a cDNA was constructed so that transcription by T7 RNA polymerase
      yielded a approximately 1-kb negative-sense analog of genomic RNA of human
      respiratory syncytial virus (RSV) containing the gene for chloramphenicol
      acetyltransferase (CAT) under the control of putative RSV transcription motifs
      and flanked by the RSV genomic termini. When transfected into RSV-infected cells,
      this minigenome was "rescued," as evidenced by high levels of CAT expression and
      the production of transmissible particles which propagated and expressed high
      levels of CAT expression during serial passage (P.L. Collins, M. A. Mink, and D.
      S. Stec, Proc. Natl. Acad. Sci. USA, 88:9663-9667, 1991). Here, this cDNA,
      together with a second one designed to yield an exact-copy positive-sense RSV-CAT
      RNA antigenome, were each modified to contain a self-cleaving hammerhead ribozyme
      for the generation of a nearly exact 3' end. Each cDNA was transfected into cells
      infected with a vaccinia virus recombinant expressing T7 RNA polymerase, together
      with plasmids encoding the RSV N, P, and L proteins, each under the control of a
      T7 promoter. When the plasmid-supplied template was the mini-antigenome, the
      minigenome was produced. When the plasmid-supplied template was the minigenome,
      the products were mini-antigenome, subgenomic polyadenylated mRNA and progeny
      minigenome. Identification of progeny minigenome made from the plasmid-supplied
      minigenome template indicates that the full RSV RNA replication cycle occurred.
      RNA synthesis required all three RSV proteins, N, P, and L, and was ablated
      completely by the substitution of Asn for Asp at position 989 in the L protein.
      Thus, the N, P, and L proteins were sufficient for the synthesis of correct
      minigenome and antigenome, but this was not the case for subgenomic mRNA,
      indicating that the requirements for RNA replication and transcription are not
      identical. Complementation with N, P, and L alone yielded an mRNA pattern
      containing a large fraction of molecules of incomplete, heterogeneous size. In
      contrast, complementation with RSV (supplying all of the RSV gene products)
      yielded a single discrete mRNA band. Superinfection with RSV of cells staging
      N/P/L-based RNA synthesis yielded the single discrete mRNA species. Some
      additional factor supplied by RSV superinfection appeared to be involved in
      transcription, the most obvious possibility being one or more additional RSV gene
      products.

PMID- 7637015
TI  - Mapping domains of retroviral integrase responsible for viral DNA specificity and
      target site selection by analysis of chimeras between human immunodeficiency
      virus type 1 and visna virus integrases.
AB  - Human immunodeficiency virus type 1 (HIV-1) and visna virus integrases were
      purified from a bacterial expression system and assayed on oligonucleotide
      substrates derived from each terminus of human immunodeficiency virus type 1 and
      visna virus linear DNA. Three differences between the proteins were identified,
      including levels of specific 3'-end processing, patterns of strand transfer, and
      target site preferences. To map domains of integrase (IN) responsible for viral
      DNA specificity and target site selection, we constructed and purified chimeric
      proteins in which the N-terminal, central, and C-terminal regions of these
      lentiviral integrases were exchanged. All six chimeric proteins were active for
      disintegration, demonstrating that the active site in the central region of each
      chimera maintained a functional conformation. Analysis of endonucleolytic
      processing activity indicated that the N terminus of IN does not contribute to
      viral DNA specificity; this function must reside in the central region or C
      terminus of IN. In the viral DNA integration assay, chimeric proteins gave novel
      patterns of strand transfer products which did not match that of either wild-type
      IN. Thus, target site selection with a viral DNA terminus as nucleophile could
      not be mapped to regions of IN defined by these boundaries and may involve
      interactions between regions. In contrast, when target site preferences were
      monitored with a new assay in which glycerol stimulates IN-mediated cleavage of
      nonviral DNA, chimeras clearly segregated between the two wild-type patterns.
      Target site selection for this nonspecific alcoholysis activity mapped to the
      central region of IN. This report represents the first detailed description of
      functional chimeras between any two retroviral integrases.

PMID- 7637016
TI  - Functional interactions between herpes simplex virus immediate-early proteins
      during infection: gene expression as a consequence of ICP27 and different domains
      of ICP4.
AB  - Two of the five immediate-early gene products, ICP4 and ICP27, expressed by
      herpes simplex virus type 1 have profound effects on viral gene expression and
      are absolutely essential for virus replication. Functional interactions between
      ICP4 and ICP27 may contribute to establishing the program of viral gene
      expression that ensues during lytic infection. To evaluate this possibility,
      viral mutants simultaneously deleted for ICP27 and defined functional domains of
      ICP4 were constructed. These mutant viruses allowed a comparison of gene
      expression as a function of different domains of ICP4 in the presence and absence
      of ICP27. Gene expression in the absence of both ICP4 and ICP27 was also
      examined. The results of this study demonstrate a clear involvement for ICP27 in
      the induction of early genes, in addition to its known role in enhancing late
      gene expression during viral infection. In the absence of both ICP4 and ICP27,
      viral early gene expression, as measured by the accumulation of thymidine kinase
      and ICP6 messages was dramatically reduced relative to the amounts of these
      messages seen in the absence of only ICP4. Therefore, elevated levels of early
      gene expression as a consequence of ICP27 occurred in the absence of any ICP4
      activity. Evidence is also presented regarding the modulation of the ICP4
      repression function by ICP27. When synthesized in the absence of ICP27, a mutant
      ICP4 protein was impaired in its ability to repress transcription from the L/ST
      promoter in the context of viral infection and in vitro. This defect correlated
      with the loss of the ability of this mutant protein to bind to its recognition
      sequence when produced in infected cells in the absence of ICP27. These
      observations indicate that ICP27 can regulate the activity of at least one domain
      of the ICP4 protein as well as contribute to elevated early gene expression
      independently of ICP4.

PMID- 7637017
TI  - Nucleocapsid protein effects on the specificity of retrovirus RNA encapsidation.
AB  - We have analyzed the roles of Gag protein nucleocapsid (NC) domains in the
      packaging or encapsidation of retroviral RNAs into virus particles. We found that
      mutation of both zinc finger motifs of the human immunodeficiency virus (HIV) NC
      domain reduced but did not eliminate encapsidation of the HIV viral RNA. However,
      the NC mutations also resulted in a three- to fourfold reduction in the
      specificity of RNA encapsidation, as determined by comparison of virus-associated
      genomic and spliced RNA levels. As a complementary approach, we replaced the NC
      domain of Moloney murine leukemia virus (M-MuLV) with that of HIV. Chimeric virus
      particles assembled efficiently, were of wild-type M-MuLV density, and cross
      linked at NC cysteines. In encapsidation studies, wild-type M-MuLV precursor Gag
      (PrGag) proteins packaged M-MuLV transcripts more efficiently than HIV RNAs. In
      contrast, chimeric PrGag proteins possessing the HIV-1 NC domain in the context
      of the M-MuLV MA (matrix), p12, and CA (capsid) domains encapsidated HIV
      transcripts to a greater extent than M-MuLV transcripts. Our results support the
      notion that retroviral NC domains contribute toward both the efficiency and
      specificity of viral genomic RNA packaging.

PMID- 7637018
TI  - A human recombinant Fab identifies a human immunodeficiency virus type 1-induced
      conformational change in cell surface-expressed CD4.
AB  - To explore the role of the CD4 molecule in human immunodeficiency virus (HIV)
      infection following initial virus-CD4 binding, we have characterized CD4-specific
      antibodies raised by immunizing an HIV-1-infected human with human recombinant
      soluble CD4 (rsCD4). Fabs were selected from a human recombinant Fab library
      constructed from the bone marrow of this immunized individual. Here, we describe
      a human rsCD4-specific recombinant Fab clone selected by panning the library over
      complexes of human rsCD4 and recombinant HIV-1 envelope protein. While this Fab
      does not bind to CD4-positive T-cell lines or to human T lymphocytes, it
      recognizes cell surface-expressed CD4 following the incubation of these cells
      with a recombinant form of HIV-1 gp120 or with HIV-1 virions. The Fab is not HIV
      1 envelope specific, since it does not bind to recombinant gp120 or to native
      cell surface-expressed HIV-1 envelope proteins. As confirmation of its CD4
      specificity, we show that this Fab immunoprecipitates a 55-kDa protein,
      corresponding to the molecular mass of cellular CD4, from an H9 cell lysate. The
      specificity of this human Fab provides evidence for a virus-induced
      conformational change in cell surface-expressed on CD4. The characterization of
      this altered CD4 conformation and its effects on the host cell will be important
      in defining postbinding events in HIV infection.

PMID- 7637019
TI  - Persistence of attenuated rev genes in a human immunodeficiency virus type 1
      infected asymptomatic individual.
AB  - With the goal of examining the functional diversity of human immunodeficiency
      virus type 1 (HIV-1) env genes within the peripheral blood mononuclear cells of
      an asymptomatic individual, we substituted four complete env genes into the
      replication-competent NL4-3 provirus. Despite encoding full-length open reading
      frames for gp120 and gp41 and the second coding exon of tat and rev, each chimera
      was replication defective. Site-directed mutagenesis of codon 78 in the Rev
      activation domain (from a hitherto unique Ile to the subtype B consensus Leu)
      partially restored infectivity for two of three chimeras tested. Similarly,
      mutagenesis of rev codon 78 of NL4-3 from Leu to Ile partially attenuated this
      virus. Ile-78 was found in all 13 clones examined from samples taken from this
      asymptomatic subject 4.5 years after infection, including 9 from peripheral blood
      mononuclear cells and 4 from a virus isolate, as well as 4 additional clones each
      from peripheral blood mononuclear cells sampled 37 and 51 months later. We next
      examined conservation of the Rev activation domain within and among long-term
      survivors (LTS) and patients with AIDS, as well as T-cell-line-adapted strains of
      HIV-1. Putative attenuating mutations were found in a minority of sequences from
      all five LTS and two of four patients with AIDS. Of the 11 T-cell-line-adapted
      viruses examined, none had these changes. Among and within LTS virus population
      had marginally higher levels of diversity in Rev than in Env; patients with AIDS
      had similar levels of diversity in the two reading frames; and T-cell-line
      adapted viruses had higher levels of diversity in Env. These results are
      consistent with the hypothesis that asymptomatic individuals harbor attenuated
      variants of HIV-1 which correlate with and contribute to their lack of disease
      progression.

PMID- 7637020
TI  - The 5' ends of Hantaan virus (Bunyaviridae) RNAs suggest a prime-and-realign
      mechanism for the initiation of RNA synthesis.
AB  - We examined the 5' ends of Hantaan virus (HTN) genomes and mRNAs to gain insight
      into the manner in which these chains were initiated. Like those of all members
      of the family Bunyaviridae described so far, the HTN mRNAs contained 5' terminal
      extensions that were heterogeneous in both length and sequence, presumably
      because HTN also "cap snatches" host mRNAs to initiate the viral mRNAs.
      Unexpectedly, however, almost all of the mRNAs contained a G residue at position 
      1, and a large fraction also lacked precisely one of the three UAG repeats at the
      termini. The genomes, on the other hand, commenced with a U residue at position
      +1, but only 5' monophosphates were found here, indicating that these chains may
      not have initiated with UTP at this position. Taken together, these unusual
      findings suggest a prime-and-realign mechanism of chain initiation in which mRNAs
      are initiated with a G-terminated host cell primer and genomes with GTP, not at
      the 3' end of the genome template but internally (opposite the template C at
      position +3), and after extension by one or a few nucleotides, the nascent chain
      realigns backwards by virtue of the terminal sequence repeats, before processive
      elongation takes place. For genome initiation, an endonuclease, perhaps that
      involved in cap snatching, is postulated to remove the 5' terminal extension of
      the genome, leaving the 5' pU at position +1.

PMID- 7637021
TI  - The rotavirus nonstructural glycoprotein NSP4 mobilizes Ca2+ from the endoplasmic
      reticulum.
AB  - We previously reported that expression of rotavirus nonstructural glycoprotein
      NSP4 is responsible for an increase in cytosolic free Ca2+ concentration
      ([Ca2+]i) in Spodoptera frugiperda (Sf9) insect cells (P. Tian, Y. Hu, W. P.
      Schilling, D. A. Lindsay, J. Eiden, and M. K. Estes, J. Virol. 68:251-257, 1994).
      The purpose of the present study was to determine the mechanism by which NSP4
      causes an increase in [Ca2+]i by measuring the permeability of the cytoplasmic
      and endoplasmic reticulum (ER) membranes in recombinant-baculovirus-infected Sf9
      cells. No obvious change in plasmalemma permeability to divalent cations was
      observed in cells expressing NSP4 compared with that in cells expressing another
      rotaviral glycoprotein (VP7) when the influx of Ba2+, a Ca2+ surrogate, was
      monitored. The basal Ca2+ permeability of the internal Ca2+ store was evaluated
      by measuring the release of Ca2+ induced by ionomycin, a Ca2+ ionophore, or
      thapsigargin, an inhibitor of the ER Ca(2+)-ATPase pump, following suspension of
      the cells in Ca(2+)-free extracellular buffer. Releasable Ca2+ decreased with
      time to a greater extent in cells expressing NSP4 compared with that in cells
      expressing VP7, suggesting that NSP4 increases the basal Ca2+ permeability of the
      ER membrane. To determine the possible mechanism by which NSP4 increases ER
      permeability, purified NSP4 protein or a 22-amino-acid synthetic peptide
      consisting of residues 114 to 135 (NSP4(114-135) was added exogenously to
      noninfected Sf9 cells during measurement of [Ca2+]i. Both NSP4 and the NSP4(114
      135 peptide produced a time-dependent increase in [Ca2+]i that was attenuated by
      prior inhibition of phospholipase C with U-73122. Pretreatment of the cells with
      thapsigargin completely blocked the increase in [Ca2+]i produced by NSP4(114-135,
      but the peptide only partially reduced the change in [Ca2+]i produced by
      thapsigargin. No changes in [Ca2+]i were seen in cells treated with control
      peptides. These results suggest that (i) exogenous NSP4 increases [Ca2+]i through
      the activation of phospholipase C, (ii) Ca2+ release by exogenous NSP4 is from a
      store that is a subset of the thapsigargin-sensitive compartment, and (iii) amino
      acid residues 114 to 135 of NSP4 are sufficient for this activity. In contrast to
      exogenous NSP4, the mechanism by which endogenously expressed NSP4 increases
      [Ca2+]1 appears to be unrelated to phospholipase C, since no effect of U-73122
      was seen on the elevated [Ca2+]1 in cells expressing NSP4 and exogenously applied
      NSP4(114-135) caused a further increase in [Ca2+]1 in cells expressing NSP4
      protein.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7637023
TI  - Receptor binding site-deleted foot-and-mouth disease (FMD) virus protects cattle
      from FMD.
AB  - Binding of foot-and-mouth disease virus (FMDV) to cells requires an arginine
      glycine-aspartic acid (RGD) sequence in the capsid protein VP1. We have
      genetically engineered an FMDV in which these three amino acids have been
      deleted, producing a virus particle which is unable to bind to cells. Cattle
      vaccinated with these receptor binding site-deleted virions were protected from
      disease when challenged with a virulent virus, demonstrating that these RGD
      deleted viruses could serve as the basis for foot-and-mouth disease vaccines
      safer than those currently in use. This strategy may prove useful in the
      development of vaccines for other viral diseases.

PMID- 7637022
TI  - Nucleotide sequence variation of the envelope protein gene identifies two
      distinct genotypes of yellow fever virus.
AB  - The evolution of yellow fever virus over 67 years was investigated by comparing
      the nucleotide sequences of the envelope (E) protein genes of 20 viruses isolated
      in Africa, the Caribbean, and South America. Uniformly weighted parsimony
      algorithm analysis defined two major evolutionary yellow fever virus lineages
      designated E genotypes I and II. E genotype I contained viruses isolated from
      East and Central Africa. E genotype II viruses were divided into two sublineages:
      IIA viruses from West Africa and IIB viruses from America, except for a 1979
      virus isolated from Trinidad (TRINID79A). Unique signature patterns were
      identified at 111 nucleotide and 12 amino acid positions within the yellow fever
      virus E gene by signature pattern analysis. Yellow fever viruses from East and
      Central Africa contained unique signatures at 60 nucleotide and five amino acid
      positions, those from West Africa contained unique signatures at 25 nucleotide
      and two amino acid positions, and viruses from America contained such signatures
      at 30 nucleotide and five amino acid positions in the E gene. The dissemination
      of yellow fever viruses from Africa to the Americas is supported by the close
      genetic relatedness of genotype IIA and IIB viruses and genetic evidence of a
      possible second introduction of yellow fever virus from West Africa, as
      illustrated by the TRINID79A virus isolate. The E protein genes of American IIB
      yellow fever viruses had higher frequencies of amino acid substitutions than did
      genes of yellow fever viruses of genotypes I and IIA on the basis of comparisons
      with a consensus amino acid sequence for the yellow fever E gene. The great
      variation in the E proteins of American yellow fever virus probably results from
      positive selection imposed by virus interaction with different species of
      mosquitoes or nonhuman primates in the Americas.

PMID- 7637024
TI  - DNA-based immunization with chimeric vectors for the induction of immune
      responses against the hepatitis C virus nucleocapsid.
AB  - Vectors expressing the first 58 amino acids of the hepatitis C virus (HCV)
      nucleocapsid alone or as a fusion protein with the middle (pre-S2 and S) or major
      (S) surface antigens of hepatitis B virus (HBV) were constructed. Intramuscular
      immunization of BALB/c mice with the chimeric constructs in the form of naked DNA
      elicited humoral responses to antigens from both viruses within 2 to 6 weeks
      postinjection. No anti-HCV responses were obtained in mice immunized with the
      vector expressing the HCV sequence in the nonfusion context. Sera from chimera
      injected mice specifically recognized both HCV capsid and HBV surface antigens in
      enzyme-linked immunosorbent assay and immunoblot testing. Anti-HCV serum titers
      formed plateaus of approximately 1:3,000; these remained stable until the end of
      the study (18 weeks postinfection). Anti-HBV immune responses were found to be
      lower in the chimera-injected animals (< 200 mIU/ml) than in those immunized with
      the native HBV vector (> 2,000 mIU/ml). This is the first report of the use of
      DNA-based immunization for the generation of immune responses to an HCV protein.
      In addition, these findings show that it is possible to elicit responses to viral
      epitopes from two distinct viruses via DNA immunization with chimeric vectors.

PMID- 7637025
TI  - The amino terminus of Tax is required for interaction with the cyclic AMP
      response element binding protein.
AB  - Tax of human T-cell leukemia virus type 1 was analyzed for interaction with the
      cyclic AMP response element binding protein (CREB) in vitro with and without Tax
      response element DNA. Mutations in the carboxy terminus of Tax (L296G and L320G)
      did not affect binding to CREB and led to supershifts. In contrast, mutants with
      changes in the amino-terminal cysteine-rich region lost the ability to bind to
      CREB. The S10A mutant protein bound moderately. Thus, the amino terminus of Tax
      is essential for Tax-CREB interaction.

PMID- 7637026
TI  - Two independent pathways of expression lead to self-assembly of the rabbit
      hemorrhagic disease virus capsid protein.
AB  - The rabbit hemorrhagic disease virus capsid protein was expressed in insect cells
      either as an individual protein species, from a mRNA analogous to the viral
      subgenomic RNA, or as part of a polyprotein that included the viral 3C-like
      protease and the RNA polymerase. Both pathways of expression led to the assembly
      of viruslike particles morphologically and antigenically similar to purified
      virus.

PMID- 7637027
TI  - Synthesis and secretion of recombinant tick-borne encephalitis virus protein E in
      soluble and particulate form.
AB  - A quantitative study was performed to investigate the requirements for secretion
      of recombinant soluble and particulate forms of the envelope glycoprotein E of
      tick-borne encephalitis (TBE) virus. Full-length E and a carboxy terminally
      truncated anchor-free form were expressed in COS cells in the presence and
      absence of prM, the precursor of the viral membrane protein M. Formation of a
      heteromeric complex with prM was found to be necessary for efficient secretion of
      both forms of E, whereas only low levels of anchor-free E were secreted in the
      absence of prM. The prM-mediated transport function could also be provided by
      coexpression of prM and E from separate constructs, but a prM-to-E ratio of
      greater than 1:1 did not further enhance secretion. Full-length E formed stable
      intracellular heterodimers with prM and was secreted as a subviral particle,
      whereas anchor-free E was not associated with particles and formed a less stable
      complex with prM, suggesting that prM interacts with both the ectodomain and
      anchor region of E.

PMID- 7637028
TI  - The capsid determinant of fibrotropism for the MVMp strain of minute virus of
      mice functions via VP2 and not VP1.
AB  - The minute virus of mice, prototype strain MVMp, productively infects cultured
      murine fibroblasts but not T cells. The immunosuppressive strain, MVMi, shows the
      converse tropism. These reciprocal tropisms are mediated by the viral capsids, in
      which their determinants have been mapped to a few specific amino acids in the
      primary sequence shared by VP1 and VP2. Which of these proteins is relevant in
      presenting these determinants during infection is not known. We have approached
      this question using a recombinant parvovirus system in which a LuIII-derived
      transducing genome, containing the luciferase reporter in place of viral coding
      sequences, can be packaged by capsid proteins from separate helper sources. We
      generated transducing virions by using helper constructs expressing either VP1 or
      VP2, containing the MVMp or MVMi tropic determinant region, in various
      combinations. The virions were used to infect human NB324K cells and murine A9
      fibroblasts. Transduction of the human cells (permissive for both MVMp and MVMi)
      required both VP1 and VP2 and was successful with all combinations of these
      proteins. In contrast, significant transducing activity for A9 cells was detected
      only with recombinant virions containing VP2 of MVMp, while the use of either
      source of VP1 had little effect. We conclude that VP2 from MVMp is necessary to
      enable infection of murine A9 fibroblasts.

PMID- 7637030
TI  - High levels of anti-human immunodeficiency virus type 1 (HIV-1) memory cytotoxic
      T-lymphocyte activity and low viral load are associated with lack of disease in
      HIV-1-infected long-term nonprogressors.
AB  - Lack of disease in long-term nonprogressors with human immunodeficiency virus
      type 1 (HIV-1) infection was strongly associated with very low copy numbers of
      HIV-1 DNA and RNA in peripheral blood mononuclear cells and plasma and the
      presence of high levels of anti-HIV-1 CD8+ memory cytotoxic T lymphocytes
      specific for Gag, Pol, and Env, compared with levels present in intermediate and
      advanced progressors. CD8+ memory cytotoxic T lymphocytes may have an important
      role in controlling HIV-1 replication and preventing disease in long-term
      nonprogressors.

PMID- 7637029
TI  - Inhibition of protein phosphorylation modulates expression of the Jak family
      protein tyrosine kinases.
AB  - Treatment of murine Friend cells with a dose of the protein kinase inhibitor
      staurosporine, which is able to block the response of the cells to interferons,
      appears to inhibit phosphorylation of Jak proteins and, interestingly, to
      specifically reduce tyk2 and Jak1 expression and to increase Jak2 both in the
      presence and in the absence of interferons. Therefore, a potential role for
      phosphorylation events in the regulation of expression of the Jak family members
      is suggested.

PMID- 7637031
TI  - Transcriptional regulation of human JC polyomavirus promoters by cellular
      proteins YB-1 and Pur alpha in glial cells.
AB  - Transcription of the human polyomavirus (JCV) genome is regulated by host cell
      proteins and the viral early protein, T antigen. A region called the lytic
      control element (LCE), located within the enhancer of JCV, is important for
      transcription of JCV early and late promoters. Earlier studies have led to the
      identification of two single-stranded DNA-binding proteins, YB-1 and Pur alpha,
      with the ability to interact with nucleotides on the early and late strands of
      LCE, respectively. Of particular interest is the notion that the unique interplay
      between these two cellular proteins and JCVT antigen determines their binding
      activities with the LCE. In this study, we employed a series of cotransfection
      experiments to evaluate the levels of transcription from JCV early and late
      promoters in the presence of YB-1, Pur alpha, and T antigen. Results from these
      studies indicated that Pur alpha stimulates JCV early and has little effect on
      the late promoter. Moreover, T antigen was able to decrease the induced level of
      early gene transcription by Pur alpha. On the other hand, the extent of
      transactivation of the viral late promoter by T antigen was reduced upon
      overexpression of Pur alpha in the transfected cells. These observations suggest
      that Pur alpha and T antigen exert an antagonistic effect on each other's
      regulatory action upon their responsive promoters. Of particular interest was the
      observation that YB-1 liberated T-antigen-induced late promoter activity from
      repression imposed by overexpression of pur alpha. Under similar conditions,
      overexpression of YB-1 showed no effect on the transcriptional activity of the
      early promoter in cells transfected with T-antigen- and Pur alpha-producing
      plasmids. On the basis of the data presented here and the previous binding
      results, a model is proposed which describes the potential role of Pur alpha, YB
      1, and T antigen in differential expression of the viral genome during the lytic
      cycle.

PMID- 7637032
TI  - Infectious cDNA clones of echovirus 12 and a variant resistant against the
      uncoating inhibitor rhodanine differ in seven amino acids.
AB  - Determination of the complete sequences of echovirus 12 and a rhodanine-resistant
      variant revealed seven amino acid deviations and two additional exchanges not
      confirmed in all clones. In rhodanine sensitivity assays with infectious cDNAs,
      it was shown that the biological markers of the original viruses are maintained.

PMID- 7637033
TI  - Immune responses to plasmid DNA encoding the hepatitis C virus core protein.
AB  - Hepatitis C virus (HCV) is a major causative agent of parenterally transmitted
      non-A, non-B hepatitis. The genomic region encoding the virion-associated core
      protein is relatively conserved among HCV strains. To generate a DNA vaccine
      capable of expressing the HCV core protein, the genomic region encoding amino
      acid residues 1 to 191 of the HCV-1 strain was amplified and cloned into an
      eukaryotic expression vector. Intramuscular inoculation of recombinant plasmid
      DNA into BALB/c mice (H-2d) generated core-specific antibody responses,
      lymphoproliferative responses, and cytotoxic T-lymphocyte activity. Our results
      suggest that the HCV core polynucleotide warrants further investigation as a
      potential vaccine against HCV infection.

PMID- 7637034
TI  - Sequences within the parvovirus minute virus of mice NS2-specific exon are
      required for inclusion of this exon into spliced steady-state RNA.
AB  - When the minute virus of mice NS2-specific exon was modified by either
      substitution or deletion, most P4-generated pre-mRNA was spliced from the large
      intron donor at nucleotide 514 to the small-intron acceptor at nucleotide 2377.
      Improvement to consensus of large-intron splice sites in such mutants did not
      suppress exon skipping or restore large-intron excision. Therefore, sequences
      within the NS2-specific exon are required for inclusion of this exon into
      spliced, steady-state minute virus of mice RNA.

PMID- 7637035
TI  - Innate resistance to lethal mousepox is genetically linked to the NK gene complex
      on chromosome 6 and correlates with early restriction of virus replication by
      cells with an NK phenotype.
AB  - Most inbred strains of mice, including DBA/2 (D2), are highly susceptible to the
      lethal effects of ectromelia virus, but C57BL/6 (B6) mice are innately resistant.
      Resistance is controlled by multiple, unlinked, autosomal dominant genes. Of 101
      male (B6 x D2)F1 x D2 backcrossed (N2) mice, 18 died after ectromelia virus
      challenge and all were homozygous for the D2 allele at the proline-rich protein
      (Prp) locus on distal chromosome 6 (P < 0.001). This association was suggested by
      the patterns of susceptibility to lethal mousepox in recombinant inbred strains
      derived from B6 and D2 mice (D. G. Brownstein, P. N. Bhatt, L. Gras, and R. O.
      Jacoby, J. Virol. 65:1946-1951, 1991). The association between the Prp locus and
      susceptibility to lethal mousepox also held for N2 male mice that were castrated
      as neonates, which increased the percentage that were susceptible to 40. Spleen
      virus titers were significantly augmented in B6 (NK1.1+) mice depleted of asialo
      GM1+ or NK1.1+ cells, whereas spleen virus titers were unaffected in D2 (NK1.1-)
      mice depleted of asialo GM1+ cells. These results suggest that a gene or genes
      within the natural killer gene complex, adjacent to the Prp locus, determine
      strain variations in resistance to lethal ectromelia virus infection.

PMID- 7637036
TI  - Fate of the human immunodeficiency virus type 1 provirus in infected cells: a
      role for vpr.
AB  - We investigated the fate of human immunodeficiency virus type 1 (HIV-1) viral DNA
      in infected peripheral blood lymphocytes and immortalized T-cell lines by using a
      replication-defective HIV-1. We observed that integrated HIV-1 DNA and viral gene
      expression decrease over time. A frameshift mutation in vpr resulted in
      maintenance of the HIV-1 provirus and stable persistence of viral expression.
      Transfection of vpr together with the neomycin resistance gene in the absence of
      other viral genes decreased the formation of geneticin-resistant colonies,
      indicating either a cytotoxic or a cytostatic effect upon cells. Therefore,
      maintenance of HIV-1 infection within an infected proliferating population is due
      to two competing processes, the rate of viral spread and the degree of cell
      growth inhibition and/or death induced by Vpr.

PMID- 7637037
TI  - Tumor necrosis factor expression during mouse hepatitis virus-induced
      demyelinating encephalomyelitis.
AB  - Neutralizing anti-tumor necrosis factor alpha (TNF-alpha) antibody treatment of
      mice infected with the neurotropic JHMV strain of mouse hepatitis virus showed no
      reduction of either virus-induced encephalomyelitis or central nervous system
      demyelination. TNF-alpha-positive cells were present in the central nervous
      system during infection; however, TNF-alpha could not be colocalized with JHMV
      infected cells. In vitro, TNF-alpha mRNA rapidly accumulated following JHMV
      infection; however, no TNF-alpha was secreted because of inhibition of
      translation. Both live and UV-inactivated virus inhibited TNF-alpha secretion
      induced by lipopolysaccharide. These data show that TNF-alpha is not secreted
      from infected cells and indicate that if contributes to either JHMV-induced acute
      encephalomyelitis nor primary demyelination.

PMID- 7637038
TI  - Sequences in the human immunodeficiency virus type 1 U3 region required for in
      vivo and in vitro integration.
AB  - A series of mutants with alterations in the U3 region of the human
      immunodeficiency virus type 1 long terminal repeat were made, and the effects of
      these mutations were evaluated both in vitro and in vivo. When the subterminal 6
      to 8 nucleotides of the U3 long terminal repeat were mutated, the resulting
      provirus was unable to efficiently replicate in vivo, and a mutant
      oligonucleotide which mimicked the mutation could not be efficiently cleaved but
      could be joined to target DNA by wild-type recombinant integrase protein in
      vitro. These results suggest that this region is important in the specific
      recognition of the viral DNA by the integrase protein.

PMID- 7637039
TI  - Efficient magnesium-dependent human immunodeficiency virus type 1 integrase
      activity.
AB  - The integrase protein from human immunodeficiency virus type 1 (HIV-1) has
      generally been reported to require Mn2+ for efficient in vitro activity. We have
      reexamined the divalent metal ion requirements of HIV-1 integrase and find that
      the protein is capable of promoting efficient 3' processing and DNA strand
      transfer with either Mn2+ or Mg2+. The metal ion preference depended upon the
      reaction conditions. HIV-1 integrase displayed significantly less nonspecific
      nuclease activity in reaction mixtures containing Mg2+ than it did under the
      previously described reaction conditions with mixtures containing Mn2+.

PMID- 7637040
TI  - In vivo activity of the hepatitis B virus core promoter: tissue specificity and
      temporal regulation.
AB  - The contribution of the hepatitis B virus enhancers I and II in the regulation of
      the activity of the core and the X promoters was assessed in transgenic mice.
      Surprisingly, despite the presence of heterologous promoters linked 5' of the X
      gene, the transgene expression is mostly due to core promoter (Cp) activity
      present in the X coding sequence. Moreover, the restriction of Cp activity to
      hepatic tissue required the combined action of both enhancers I and II, whereas
      the proximity of these two enhancers was insufficient to confer tissue
      specificity on Xp activity. Furthermore, the liver-specific activity of the Cp
      was developmentally regulated in an enhancer I-independent manner.

PMID- 7637041
TI  - The tax mutation at nucleotide 7959 of human T-cell leukemia virus type 1 (HTLV
      1) is not associated with tropical spastic paraparesis/HTLV-1-associated
      myelopathy but is linked to the cosmopolitan molecular genotype.

PMID- 7637042
TI  - Operative reconstruction of the external and internal genitalia in female
      patients with bladder exstrophy or incontinent epispadias.
AB  - PURPOSE: Urologists and gynecologists rarely encounter questions on cohabitation
      and pregnancy in female patients with bladder exstrophy or incontinent
      epispadias. MATERIALS AND METHODS: Until 1994, 41 female patients underwent
      surgery at our institution (vaginal cutback or vaginoplasty in 23, correction of
      the external genitalia in 25 and uterus fixation to correct or prevent prolapse
      in 13). RESULTS: Followup was available in 37 patients (mean 16.8 years, with
      followup of 18 years or longer in 19). Of the patients 94% are satisfied with the
      cosmetic results. All adults engage in sexual intercourse, 4 delivered 6 children
      by cesarean section and 5 presently desire children. CONCLUSIONS: Fertility in
      patients with bladder exstrophy or incontinent epispadias is normal, and
      pregnancy is possible. Patients and parents should be well informed. Besides
      urinary tract reconstruction, correction of the external and internal genitalia
      should be discussed in detail.

PMID- 7637044
TI  - The polypropylene pubovaginal sling for the treatment of recurrent stress urinary
      incontinence.
AB  - PURPOSE: The significance of a 2-team approach to the problems of recurrent
      incontinence in patients with extensive pelvic scarring from previous surgery is
      emphasized. MATERIALS AND METHODS: We reviewed 88 consecutive patients who
      presented between January 1986 and November 1992. The demonstration of a scarred,
      wide open, proximal urethra or drain pipe urethra was the important selection
      criterion. Two teams, 1 operating abdominally and 1 vaginally, released the
      bladder neck from its bed of scar under direct vision and set the sling in place
      with minimal tension at the bladder neck. RESULTS: Of the women 75 (85.2%) were
      cured of the stress urinary incontinence and 8 (9.1%) had improvement with mainly
      urge incontinence, while 5 (5.7%) operations failed. There was a significant
      association between chronic chest disease and failure. CONCLUSIONS: The 2-team
      polypropylene (Marlex) mesh approach continues to be an effective treatment for
      women with complicated stress urinary incontinence.

PMID- 7637045
TI  - Papaverine-phentolamine and prostaglandin E1 versus papaverine-phentolamine alone
      for intracorporeal injection therapy: a clinical double-blind study.
AB  - PURPOSE: A study was designed to compare intracorporeal injections of papaverine
      plus phentolamine (2-drug solution) and papaverine plus phentolamine and
      prostaglandin E1 (3-drug solution) for the treatment for impotence. MATERIALS AND
      METHODS: A total of 20 impotent patients received intracorporeal injections of
      the 2-drug or 3-drug solution alternately during 2 sessions, and the quality and
      duration of erections were assessed. RESULTS: Of the patients 73% achieved a full
      erection with the 3-drug solution compared to 28% with the 2-drug solution. The
      average duration of erections was 57 minutes and 33.6 minutes, respectively. The
      complication rate was similar for the 2 treatments. CONCLUSIONS: Papaverine plus
      phentolamine and prostaglandin E1 is superior to papaverine plus phentolamine
      alone for the treatment of impotence.

PMID- 7637043
TI  - Transvaginal sacrospinous ligament fixation for treatment of vaginal prolapse.
AB  - PURPOSE: We performed sacrospinous ligament fixation for the treatment of vaginal
      apical prolapse in a urological practice. MATERIALS AND METHODS: A total of 24
      patients underwent sacrospinous ligament fixation for the treatment of vaginal
      prolapse. In 13 patients another procedure was done concomitantly through the
      same exposure for treatment of stress urinary incontinence and/or pelvic
      relaxation. RESULTS: At a mean followup of 13.8 months (range 4 to 26) 18 of 24
      patients had complete resolution of vaginal prolapse, while 5 had a clinically
      significant recurrence. Two patients underwent repeat sacrospinous ligament
      fixation with a good result, colpocleisis was performed in 1 and 2 are being
      managed conservatively. One patient had a cystocele postoperatively. All
      recurrences were within 6 months. Complications were uncommon. One patient
      suffered a small rectal laceration that was repaired primarily and she had no
      further clinical sequelae. If the 2 patients who underwent repeat sacrospinous
      ligament fixation are considered, the overall success rate was 87.5% (21 of 24).
      CONCLUSIONS: Sacrospinous ligament vaginal fixation can be used safely and
      effectively to treat vaginal prolapse in urological practice, either alone or
      combined with another transvaginal procedure for the treatment of stress urinary
      incontinence.

PMID- 7637046
TI  - Laser treatment of localized squamous cell carcinoma of the penis.
AB  - PURPOSE: We evaluate the efficacy and morbidity of laser and conventional
      treatment in 32 men with penile cancer. MATERIALS AND METHODS: Of 32 men treated
      for squamous cell carcinoma of the penis observed for an average of 44 months 19
      were treated with the combined carbon dioxide and neodymium: YAG lasers. The 13
      patients treated conventionally had more advanced disease and they were a mean 17
      years older than those in the laser treated group. RESULTS: All laser treated
      patients were disease-free after a mean of 31 months. Among the 13 conventionally
      treated patients there were only 5 long-term survivors. CONCLUSIONS: The cosmetic
      and functional outcome of laser treatment for stages Tis to T2N0M0, grades 1 and
      2 squamous cell carcinoma of the penis is excellent, and the associated morbidity
      rate is low.

PMID- 7637047
TI  - The detection of human papillomavirus deoxyribonucleic acid in intraepithelial,
      in situ, verrucous and invasive carcinoma of the penis.
AB  - PURPOSE: We study the prevalence of human papillomavirus deoxyribonucleic acid
      (DNA) in squamous cell carcinoma and control tissue of the penis. MATERIALS AND
      METHODS: The technique of polymerase chain reaction DNA amplification was used to
      detect specific human papillomavirus DNA sequences in archival pathological and
      control tissues. We analyzed 42 cases of invasive squamous cell carcinoma, 13 of
      carcinoma in situ, 12 of penile intraepithelial neoplasia, 3 of verrucous
      carcinoma and 25 of balanitis xerotica obliterans, as well as 29 routine neonatal
      circumcision specimens and 32 adult circumcision specimens. RESULTS: Overall, the
      detection rates for human papillomavirus DNA in the study and control tissues
      were 55% (23 of 42 cases) for invasive squamous cell carcinoma, 92% (12 of 13)
      for carcinoma in situ, 92% (11 of 12) for penile intraepithelial neoplasia, 0% (0
      of 3) for verrucous carcinoma, 4% (1 of 25) for balanitis xerotica obliterans, 0%
      (0 of 29) for neonatal circumcision and 9% (3 of 32) for adult circumcision. In
      all groups human papillomavirus type 16 was the most common genotype identified.
      CONCLUSIONS: The prevalence of human papillomavirus DNA is significantly greater
      in carcinoma of the penis than in control tissue. Moreover, the prevalence is
      greater in noninvasive lesions (carcinoma in situ and penile intraepithelial
      neoplasia) than in invasive carcinoma.

PMID- 7637048
TI  - Effects of smoking on testicular function, semen quality and sperm fertilizing
      capacity.
AB  - PURPOSE: The effects of smoking on testicular function and sperm physiology were
      studied. MATERIALS AND METHODS: Left testicular biopsy was performed in 49
      smokers and 28 nonsmokers. Seminal specimens from these men were analyzed.
      RESULTS: Testosterone levels in the left testicular vein, left testicular
      androgen-binding protein secretion rate (in vitro), sperm motility, percentage of
      morphologically normal spermatozoa, sperm morphometric parameters and outcome of
      sperm function tests were significantly lower (p < 0.05) in smokers than in
      nonsmokers. CONCLUSIONS: Morphological sperm abnormalities due to secretory
      dysfunction of the Leydig and Sertoli cells may be the cause of impaired sperm
      fertilizing capacity in smokers.

PMID- 7637049
TI  - Intermittent shedding of human immunodeficiency virus in semen: implications for
      sexual transmission.
AB  - PURPOSE: We attempt to increase our understanding of human immunodeficiency virus
      (HIV) shedding in semen. MATERIALS AND METHODS: We followed 16 seropositive men
      for up to 27 months by HIV cocultivation, with a subset evaluated using the
      polymerase chain reaction. RESULTS: The proportion with at least 1 HIV positive
      semen culture increased from 3 of 16 subjects (19%) at visit 1 to 10 (63%) by
      visit 5. Overall, HIV was cultured from 25 of 114 specimens (22%). Shedding was
      intermittent for each of the 10 men with at least 1 positive culture and seminal
      shedding patterns were highly variable. CONCLUSIONS: By culture and polymerase
      chain reaction, HIV is shed intermittently in the semen. If cultures are
      performed often enough most seropositive men shed HIV in the semen.

PMID- 7637050
TI  - Testicular seminoma: clinical significance of nuclear deoxyribonucleic acid
      ploidy pattern as studied by flow cytometry.
AB  - PURPOSE: We evaluated the clinical significance of deoxyribonucleic acid (DNA)
      ploidy pattern as a predictor of prognosis in patients with testicular seminoma.
      MATERIALS AND METHODS: Flow cytometric nuclear DNA analysis was performed on
      archival specimens from 65 patients with pure seminoma who underwent radical
      orchiectomy between 1970 and 1992. RESULTS: A total of 42 specimens (65%)
      exhibited a DNA diploid pattern, while 23 (35%) were DNA aneuploid. Diploidy was
      manifested in 73% of the stage I tumors versus 31% of stage II cancers (p =
      0.004). No correlation was found between ploidy and histological type, size or
      local extension of the tumor. Tumor progression was observed in 5 patients,
      exclusively displaying aneuploid histograms (p = 0.0017), and 3 of them
      subsequently died of the disease. CONCLUSIONS: DNA ploidy pattern may provide
      important prognostic information for patients with testicular seminoma.

PMID- 7637051
TI  - A surveillance study of clinical stage I nonseminomatous germ cell tumors of the
      testis: 10-year followup.
AB  - PURPOSE: We evaluate the 10-year results of a surveillance study of clinical
      stage I nonseminomatous germ cell tumors of the testis. MATERIALS AND METHODS:
      Between 1981 and 1984 we recruited 85 consecutive evaluable patients with
      nonseminomatous germ cell tumors of the testis and normal post-orchiectomy
      physical examination, chest x-rays, bipedal lymphangiography, abdominal scans and
      serum tumor markers. The patients were followed for at least 10 years after
      orchiectomy alone, which was performed elsewhere in 90% of the cases. RESULTS:
      The interval between visits was twice as long as it was scheduled. Relapses
      occurred in 25 patients (29.4%) after a median disease-free interval of 7 months
      (range 2 to 68). Five patients had further relapses and 3 (3.5%) died of cancer.
      Retroperitoneal relapses (19%) occurred later than lung relapses, and they were
      diagnosed when larger than 5 cm. in 7 patients. The percentage of embryonal
      carcinoma within the tumor associated with relapse (p = 0.008), T category (p =
      0.023), scrotal violation (p = 0.042) and vascular invasion (p = 0.063) had a
      weak correlation but data on T category and vascular invasion were available for
      only some patients. CONCLUSIONS: Surveillance is a difficult type of study and
      missing data may compromise the therapeutic program based on prognostic factors.

PMID- 7637052
TI  - Testis cancer--shibboleths reconsidered.

PMID- 7637053
TI  - Interpretation of bilateral positive biopsies in prostate cancer.
AB  - PURPOSE: When 6 systematic prostate needle core biopsies are positive for cancer
      bilaterally, prediction of clinical cancer volume is limited by the unpredictable
      presence of contralateral incidental tumors. Criteria were sought to improve
      prediction. MATERIALS AND METHODS: Core cancer lengths were summed unilaterally
      (3 biopsies) and bilaterally (6) in 65 patients with bilateral positive cores. Of
      the patients 31 had true bilateral cancer spread and 34 had unilateral disease
      with contralateral incidental tumors. RESULTS: For both groups correlation with
      prostatectomy cancer volume (r = 0.65, p < 0.001) was the same for the sum of 3
      ipsilateral cores as for all 6 cores. CONCLUSIONS: Core cancer length sum of 3
      ipsilateral biopsies predicts the largest prostatectomy cancer volume as well as
      the bilateral sum. Contralateral biopsies do not contribute to prediction nor
      distinguish bilateral spread from contralateral incidental cancers.

PMID- 7637054
TI  - How potent is potent before nerve sparing radical retropubic prostatectomy?
AB  - PURPOSE: We objectively evaluated potency before nerve sparing radical retropubic
      prostatectomy. MATERIALS AND METHODS: A total of 45 consecutive potent,
      neurologically normal and sexually active candidates 47 to 70 years old (mean age
      62) completed a detailed questionnaire (separate from their partner), and
      underwent penile biothesiometry, RigiScan* testing for 3 nights, and duplex
      Doppler scanning of the cavernous arteries before and after prostaglandin E1
      injection. RESULTS: Of the patients 8 noted moderate and the remainder normal
      erections on the questionnaire. RigiScan testing and penile biothesiometry
      correlated poorly with potency status. Duplex scanning demonstrated excellent
      peak velocities in 93% of the patients. CONCLUSIONS: This well studied
      prospective series underscores the importance of careful objective assessment of
      potent surgical candidates, and underlines a strong correlation between
      preoperative potency status and duplex Doppler scanning.

PMID- 7637055
TI  - Incidental appendectomy during urological surgery.
AB  - PURPOSE: To investigate the issue of incidental appendectomy during urological
      surgery we retrospectively studied its consequences in 2 groups of urological
      patients. MATERIALS AND METHODS: We studied 147 patients undergoing cystectomy
      and urinary diversion (group 1) and 200 undergoing primary retroperitoneal
      lymphadenectomy (group 2). Incidental appendectomy was performed in 122 (83%) and
      114 (57%) patients, respectively. RESULTS: The incidence of infectious
      complications in group 2 was significantly higher among patients who underwent
      incidental appendectomy compared to those without appendectomy (9.6% and 2.3%,
      respectively, p = 0.032). No difference was noted among the patients in group 1
      (10.6% and 12.0%, respectively, p = 0.51). CONCLUSIONS: When evaluating the
      prophylactic merits, incidental appendectomy can be performed safely during
      radical cystectomy and urinary diversion. It is probably contraindicated in
      patients undergoing retroperitoneal lymphadenectomy for testis cancer due to the
      apparent added risk of infectious complications.

PMID- 7637056
TI  - A new renal tourniquet for open and laparoscopic partial nephrectomy.
AB  - PURPOSE: We describe a novel double loop renal parenchymal tourniquet for
      obtaining hemostasis during open and laparoscopic partial nephrectomy. METHODS:
      One loop is positioned around the upper and 1 around the lower renal poles, thus
      securely entrapping the kidney. During partial nephrectomy the corresponding loop
      is double looped and cinched, thus achieving a tourniquet effect. The renal
      artery is not occluded. Intraoperative renal hypothermia is not required.
      RESULTS: The renal tourniquet was used clinically during 6 open and 1
      laparoscopic partial nephrectomies. Furthermore, during laparoscopic nephrectomy
      (5 porcine and 1 clinical cases) the double loop apparatus allowed for improved
      maneuverability of the kidney. CONCLUSIONS: The novel renal tourniquet affords
      adequate renal parenchymal hemostasis during open and laparoscopic partial
      nephrectomy.

PMID- 7637057
TI  - A simple nonmetal stent for treatment of urethral strictures: a preliminary
      report.
AB  - PURPOSE: A polyurethane temporary stent has been designed for urethral strictures
      in patients who are unfit or unwilling to undergo surgery. MATERIALS AND METHODS:
      The stent resembles a Malecot catheter and is inserted easily through the
      urethrotome sheath immediately after urethrotomy. The stent was used in 22
      patients with recurrent urethral strictures and was left in the urethra for 3 to
      24 months. RESULTS: Mean followup was 11.2 months. All patients were treated
      successfully and had improved urine flow rates (maximum 15 to 21 ml. per second).
      In no patient was the stent obstructed by incrustation for up to 2 years.
      CONCLUSIONS: This simple stent may offer effective treatment for many urethral
      strictures.

PMID- 7637058
TI  - Laparoscopic colpo-suspension.
AB  - PURPOSE: The feasibility of using minimally invasive laparoscopic techniques
      adhering to the surgical principles of management of anatomical stress
      incontinence was evaluated in 10 women. MATERIALS AND METHODS: Postoperative
      performances and early surgical results were compared with those of
      contemporaneous groups of women undergoing open colpo-suspension or vaginal
      needle suspension. RESULTS: Laparoscopic colpo-suspension proved to be
      technically feasible with less postoperative pain and shorter hospitalization.
      CONCLUSIONS: All 3 groups of patients had similar relief from stress incontinence
      in the early postoperative followup.

PMID- 7637059
TI  - Mucinous cystadenocarcinoma of the vermiform appendix presenting as a renal
      tumor.

PMID- 7637060
TI  - A matrix calculus causing bilateral ureteral obstruction and acute renal failure.

PMID- 7637061
TI  - Preperitoneal laparoscopic bladder hernia repair.

PMID- 7637062
TI  - Schistosomiasis: an unusual cause of hematuria in the ileal neobladder.

PMID- 7637063
TI  - Intraperitoneal urinary extravasation associated with infected urachal cyst.

PMID- 7637064
TI  - Squamous cell carcinoma arising from a suprapubic cystostomy tract with extension
      into the bladder.

PMID- 7637065
TI  - Unusual Peyronie's disease with a double-barreled appearance.

PMID- 7637066
TI  - A live birth from intracytoplasmic injection of a spermatozoon retrieved from
      testicular parenchyma.

PMID- 7637067
TI  - Resident training survey in infertility.
AB  - PURPOSE: We characterize infertility training in urology residency programs.
      MATERIALS AND METHODS: A pilot survey was sent to randomly selected urological
      training programs. The modified final survey was sent to 126 approved urological
      residencies in North America. RESULTS: Of the 126 surveys 110 (87%) were
      returned. Among the programs 38% expressed interest in recruiting a faculty
      member with expertise in infertility, 32% indicated an inadequate number of
      patients available to train residents and 56% indicated that their residents were
      least competent in the treatment of infertile patients compared to the other
      urological subspecialty disciplines. CONCLUSIONS: This survey confirms the
      underemphasis of infertility in urological training programs and the need to
      enhance this training.

PMID- 7637068
TI  - Re: Renal and diaphragmatic endometriosis de novo associated with hormone
      replacement therapy.

PMID- 7637069
TI  - Re: Circumcision revision in prepubertal boys: analysis of a 2-year experience
      and description of a technique.

PMID- 7637070
TI  - Re: Penile gangrene associated with chronic renal failure: report of 7 cases and
      review of the literature.

PMID- 7637071
TI  - Spontaneous corporal herniation of the penis: a new abnormality of the tunica
      albuginea.

PMID- 7637072
TI  - Re: Unilateral unitary inflatable penile prosthesis to correct impaired
      tumescence and severe penile deformity resulting from traumatic rupture of 1
      corpus cavernosum.

PMID- 7637073
TI  - The results of surgical therapy for cryptorchidism: a literature review and
      analysis.
AB  - PURPOSE: The literature was reviewed to consolidate the diverse success rates
      reported for orchiopexy. MATERIALS AND METHODS: A total of 64 articles pertaining
      to 8,425 undescended testicles was reviewed and found to contain evaluable data.
      Success was defined as scrotal position and lack of atrophy. RESULTS: Success
      rates by anatomical testicular position were 74% for abdominal, 82% for peeping
      and 87% for canalicular testes, and 92% for those located beyond the external
      ring. Success rates by procedure were 89% for inguinal, 67% for Fowler-Stephens,
      77% for staged Fowler-Stephens, 81% for transabdominal, 73% for 2-stage and 84%
      for microvascular orchiopexy. CONCLUSIONS: The significant failure rate for
      proximal testes suggests that efforts to improve orchiopexy should continue.

PMID- 7637074
TI  - Renal transplantation in patients with posterior urethral valves: favorable long
      term outcome.
AB  - PURPOSE: We assessed the long-term efficacy of renal transplantation in patients
      with posterior urethral valves. MATERIALS AND METHODS: We reviewed the outcome in
      23 patients with posterior urethral valves who underwent renal transplantation
      since 1979. RESULTS: Graft survival was 69% at 5 years and 63% at 10 years. Seven
      patients with followup of 7 years or longer had a mean serum creatinine level of
      1.5 mg/dl. Three patients (13%) demonstrated significant bladder dysfunction
      postoperatively. CONCLUSIONS: Renal transplantation into a valve bladder is not
      associated with an abnormally high rate of failure. Deterioration of graft
      function secondary to lower urinary tract dysfunction is uncommon, with the
      majority of patients able to use the unmodified native bladder as a receptacle
      for the transplanted kidney.

PMID- 7637075
TI  - Ureteropelvic junction repair: stent and vent.
AB  - PURPOSE: We report on a simple technique of how to stent and vent the anastomosis
      after ureteropelvic junction repair in children. MATERIALS AND METHODS: An 8F
      feeding tube housing a 4F ureteral catheter, each trimmed to different lengths,
      was used to stent a ureteropelvic junction anastomosis in a 3-year-old girl with
      1 functional kidney. On postoperative day 7 the ureteral catheter was removed and
      a nephrostogram was performed via the remaining feeding tube, which could also
      function as a nephrostomy tube. RESULTS: The combined tubes were simply
      constructed, easily cared for during the postoperative period, served the purpose
      of stenting and could provide nephrostomy drainage if necessary. CONCLUSIONS: We
      recommend our stent and vent system in select cases of ureteropelvic junction
      repair.

PMID- 7637076
TI  - Bilateral ureteral obstruction secondary to a perforated appendiceal abscess.

PMID- 7637077
TI  - Ureteroureterostomy for repair of a mid ureteral stricture using a ureter with
      vasculature based on an ileal conduit.

PMID- 7637078
TI  - Preputial continent vesicostomy: preliminary report of a new technique.

PMID- 7637079
TI  - Stomach in combination with other intestinal segments in pediatric lower urinary
      tract reconstruction.
AB  - PURPOSE: We report the results of combining gastric and ileal segments in a small
      group of predominantly pediatric patients. MATERIALS AND METHODS: We
      retrospectively reviewed the records of 6 children and 1 adult who underwent
      lower urinary tract reconstruction using stomach and ileum, including 3
      simultaneous and 4 staged procedures. Followup was 13 to 59 months. RESULTS: No
      patient had deterioration of renal function due to impaired upper tract drainage.
      One patient had an episode of hyponatremia during a gastrointestinal illness. The
      adult has the hematuria-dysuria syndrome and receives omeprazole. No ulceration
      developed in the 6 evaluable patients. CONCLUSIONS: The combined use of stomach
      and ileum has been effective in this small group of challenging patients. Long
      term followup is mandatory.

PMID- 7637080
TI  - Concealed umbilical stoma: description of a modified technique.
AB  - PURPOSE: We describe a technique for creating a concealed umbilical stoma.
      MATERIALS AND METHODS: The base of the umbilicus is used as a superiorly based
      skin flap that is incorporated into the spatulated stoma. Six patients have
      undergone diversion using this technique. The stoma was constructed from appendix
      in 4 cases, stomach in 1 and tapered ileum in 1. RESULTS: All patients achieved
      an easily catheterizable hidden umbilical stoma, are dry on clean intermittent
      catheterization and have had no stomatitis or peristomal hernia. CONCLUSIONS:
      This technique for creating a concealed umbilical stoma preserves the native
      appearance of the umbilicus and combines a superior cosmetic result with an
      easily catheterizable stoma.

PMID- 7637081
TI  - Contralateral reflux after unilateral ureteral reimplantation in patients with a
      history of resolved contralateral reflux.
AB  - PURPOSE: We determined the risk of contralateral reflux after unilateral ureteral
      reimplantation in patients with a history of resolved contralateral reflux.
      MATERIALS AND METHODS: We reviewed our experience with 53 children who underwent
      unilateral ureteral reimplantation for primary vesicoureteral reflux. RESULTS:
      Postoperative contralateral reflux occurred in 5 of 11 children (45%) with a
      history of bilateral reflux that had resolved preoperatively on the contralateral
      side and 4 of 42 (10%) with no history of contralateral reflux. CONCLUSIONS:
      Strong consideration should be given to performing bilateral ureteral
      reimplantation in children with unilateral reflux and a history of resolved
      contralateral reflux.

PMID- 7637082
TI  - The 3-loop technique: a reliable technique for anterior pubic fixation in bladder
      exstrophy.
AB  - PURPOSE: In exstrophic anomalies the ultimate urological outcome largely depends
      on successful initial closure of the lower urinary tract and soft tissues. We
      believe that secure anterior pubic fixation is crucial for ensuring successful
      closure. After being dissatisfied with other methods of anterior pubic fixation
      we introduced the 3-loop method. The 3-loop technique and our experience with it
      are described. MATERIALS AND METHODS: In 2 years 7 consecutive cases of bladder
      exstrophy were closed using the 3-loop technique. Patient age at closure ranged
      from newborn to 9 years. RESULTS: In all 7 patients closure was successful and
      there was no cutting through of the wires, bony erosion, or erosion into the
      reconstructed bladder neck or urethra. The duration of postoperative traction was
      only 2 weeks. CONCLUSIONS: The 3-loop method is useful and reliable for secure
      anterior pubic fixation of the pubes in bladder exstrophy patients and it
      contributes positively to the ultimate urological outcome.

PMID- 7637084
TI  - An honest look at bladder exstrophy.

PMID- 7637083
TI  - Urinary diversion in bladder exstrophy and incontinent epispadias: 25 years of
      experience.
AB  - PURPOSE: To determine the optimal surgical approach in achieving complete urinary
      continence with preservation of the upper urinary tract in the exstrophy
      epispadias complex we reviewed the records of patients treated at our
      institution. MATERIALS AND METHODS: From 1968 to July 1994, 115 patients with
      bladder exstrophy/incontinent epispadias were treated of whom followup was
      available for 104 and 2 died of causes unrelated to urinary diversion. Mean
      followup is 16.7 years. In 43 of the 102 patients surgery was primarily performed
      at our institution (urinary diversion in 39, a modified Young-Dees procedure in 1
      and sling plasty in 3). In another 59 patients urinary diversion was done
      secondarily after therapy elsewhere (bladder closure/bladder neck reconstruction
      in 34 and failed urinary diversion with incontinence in 22). Urinary diversion
      was performed in 49 patients, a Young-Dees procedure in 7 and genital
      reconstruction alone in 3. RESULTS: The present continence rates are 96% for the
      rectal reservoir, 97% for the Mainz pouch I and 67% for the modified Young-Dees
      augmentation. Upper tracts have remained stable and no bowel neoplasms have
      developed. CONCLUSIONS: Rectal reservoirs represent our urinary diversion of
      choice. After failed reconstruction/insufficient anal sphincter a Mainz pouch I
      is constructed and when the upper tract has deteriorated a colon conduit is
      created.

PMID- 7637085
TI  - Urodynamic findings in children with spinal cord ischemia.
AB  - PURPOSE: We identified urodynamic patterns of lower urinary tract dysfunction in
      children after anterior spinal artery injury. MATERIALS AND METHODS: Between 1981
      and 1993, 6 boys and 1 girl in whom ischemic spinal cord injuries developed after
      umbilical artery catheterization (4), cardiovascular surgery (2) and spontaneous
      bleeding from an arteriovenous fistula (1) were evaluated radiologically,
      neurologically and urodynamically. RESULTS: Neurological assessment revealed a
      motor level from T8 to S1 in all 7 children, whereas only 3 had sensory
      denervation ranging from T8 to L4. Urodynamic studies demonstrated a mixed upper
      and lower motor neuron pattern in 3 patients, a lower motor neuron lesion only in
      3 and a pure upper motor neuron deficit in 1. Treatment consisted of oxybutynin
      in 5 cases, Crede voiding in 1 and close observation in 1. All children are dry
      and kidney function has remained stable. CONCLUSIONS: Spinal cord ischemia in
      children is a rare condition that can arise from a variety of causes, the most
      common of which are embolism from umbilical artery catheterization and surgical
      repair of a patent ductus arteriosus. The urodynamic patterns are variable but
      characteristically they can be upper or lower motor neuron in nature. Precise
      testing will lead to appropriate therapy to prevent upper urinary tract disease
      and minimize incontinence.

PMID- 7637086
TI  - Quantitative histology of germ cells in the undescended testes of human fetuses,
      neonates and infants.
AB  - PURPOSE: We investigated the number of germ cells per tubular cross section and
      testicular weight in cryptorchid fetuses, neonates and infants, and characterized
      additional abnormalities. MATERIALS AND METHODS: Our series comprised 35 fetuses
      and 58 boys with cryptorchidism, and 22 normal fetuses and 25 normal boys. Age
      ranged from 28 weeks of gestation to 3 years. RESULTS: Cryptorchid fetuses had
      reduced germ cells per tubular cross section values and lower testicular weights.
      Values were reduced in cryptorchid boys without a symptomatic inguinal hernia. If
      a hernia was present, values were normal in the first year of life but decreased
      at age 1 to 3 years. Malformations or dysplasia of the kidneys, ureter or T10 to
      S5 vertebrae were present in 34% of the cryptorchid fetuses and 18% of the
      cryptorchid boys without a symptomatic inguinal hernia. CONCLUSIONS: Our study
      suggests a reduced number of germ cells in undescended testes from week 28 of
      gestation and germ cell hypoplasia as a consequence of continued postnatal
      undescended testicular position. Cryptorchidism may result from abnormal
      development of the caudal developmental field.

PMID- 7637087
TI  - Use of laparoscopy in intersex patients.
AB  - PURPOSE: Management of impalpable gonads in intersex patients remains a
      challenging problem. Since laparoscopic gonadectomy or gonadal preservation has
      been used in the management of impalpable gonads in the normal male population,
      laparoscopy can be an alternative method in the treatment of intersex patients.
      MATERIALS AND METHODS: Laparoscopic operations were performed on 6 patients with
      intersex conditions, including the testicular feminization syndrome in 2, 17 beta
      hydroxysteroid dehydrogenase deficiency in 1, 5 alpha-reductase deficiency in 1
      and mixed gonadal dysgenesis in 2. RESULTS: Laparoscopic gonadal biopsy,
      gonadectomy and hysterosalpingectomy were done in select patients. CONCLUSIONS:
      Although the initial diagnoses were made by phenotypic presentation, and
      biochemical and cytogenetic studies, laparoscopy had an important role in
      defining the internal ductal and gonadal structures to confirm the diagnosis, and
      served as an efficient method for gonadectomy and removing structures contrary to
      the assigned gender.

PMID- 7637088
TI  - The renal vascular response to acutely elevated intrapelvic pressure: resistive
      index measurements in experimental urinary obstruction.
AB  - PURPOSE: To assess the accuracy of resistive index (RI) in the diagnosis of
      obstruction. MATERIALS AND METHODS: The time course of RI and its relationship to
      intrapelvic pressure were measured in 6 dogs following unilateral obstruction.
      RESULTS: Changes in RI 1) occurred as early as 1/2 hour after acute obstruction,
      2) only reached diagnostic sensitivity after 3 to 4 hours, 3) accurately
      diagnosed obstruction whenever the RI ratio between the kidneys exceeded 1.15 and
      4) were uninfluenced by alterations in intrapelvic pressure. CONCLUSIONS: Because
      RI more closely reflects changes in renal blood flow than pelvic pressure, it can
      accurately diagnose acute obstruction but only after several hours. Diagnostic
      accuracy in chronic obstruction may be influenced by these physiologic
      relationships.

PMID- 7637089
TI  - Eicosanoid excretion from the contralateral kidney in pigs with complete
      unilateral ureteral obstruction.
AB  - PURPOSE: Eicosanoid excretion from the contralateral kidney in pigs with
      unilateral ureteral occlusion (UUO) was examined, and the effects of blockade of
      angiotensin II synthesis and cyclooxygenase inhibition were investigated.
      MATERIALS AND METHODS: Urine obtained from contralateral kidneys in pigs with UUO
      and from the right kidney in sham-operated pigs was examined for prostaglandin E2
      (PGE2) and thromboxane B2 (TxB2) by radioimmunoassay. RESULTS: Excretion rate of
      PGE2 increased from 307 +/- 69 pg. per minute to 542 +/- 149 pg. per minute (p <
      0.05) during UUO. Indomethacin blocked the synthesis of both PGE2 and TxB2.
      Administration of an inhibitor of the angiotensin I converting enzyme resulted in
      a significant (p = 0.02) reduction of PGE2 excretion as well as a decrease in
      TxB2 excretion which was significantly lower 15 hours after UUO. Blockade of
      angiotensin II synthesis in the sham-operated pigs did not affect prostanoid
      excretion from their kidneys. CONCLUSION: This study demonstrates that the
      presence of angiotensin is important for a full expression of these prostanoids
      in the contralateral kidney during UUO.

PMID- 7637090
TI  - Reversal by a dihydropyridine derivative of non-P-glycoprotein-mediated multidrug
      resistance in etoposide-resistant human prostatic cancer cell line.
AB  - PURPOSE: We have isolated etoposide-resistant prostatic cancer cell lines, P/VP10
      and P/VP20, to investigate the multidrug resistance (MDR) mechanism and to find
      MDR reversal agents. MATERIALS AND METHODS: We examined expression of MDR-related
      genes and screened reversal agents of MDR in P/VP20 cells. RESULTS: These cells
      demonstrated a non-P-glycoprotein (P-gp)-mediated MDR phenotype with
      overexpression of MDR-associated protein (MRP) mRNA due to MRP DNA amplification.
      A 1,4-dihydropyridine derivative, bis(4-pyridylmethyl)4-[2-(3-methyl-5,6- dihydro
      1,4-dithiinyl)]-2,6-dimethyl-1,4-dihydropyridine-3,5-dicar boxylate (NIK250), was
      found to overcome MDR in P/VP20 cells. CONCLUSIONS: NIK250 might be useful in
      reversing MDR, which often develops during chemotherapy of advanced or hormone
      resistant prostatic cancer.

PMID- 7637091
TI  - Effects of the peptide leukotriene receptor antagonist ICI 198,615 on the in vivo
      and in vitro changes in guinea pig bladder function which occur after
      sensitization with ovalbumin.
AB  - PURPOSE: The present studies were designed to determine the effects of in vivo
      and in vitro administration of ICI 198,615 (ICI), a leukotriene receptor
      antagonist, on the inflammatory changes that occur in the bladder after
      sensitization with ovalbumin. MATERIALS AND METHODS: The effect of intravenous
      administration of ICI on urodynamic changes after instillation of ovalbumin to
      sensitized guinea pigs was evaluated by in vivo cystometry. Responses of in vitro
      bladder muscle strips to contractile stimuli and ovalbumin were also evaluated in
      the presence of ICI. RESULTS: In sensitized guinea pigs, in vivo cystometry with
      ovalbumin induced a marked decrease in bladder capacity and increase in
      intravesical pressure. Pretreatment with ICI prior to cystometry prevented the
      ovalbumin-induced changes in capacity and intravesical pressure. There were no
      significant differences between control and sensitized animals in the responses
      of in vitro bladder muscle strips to field stimulation or bethanechol. However,
      maximal contractile responses to ovalbumin were significantly greater in the
      strips from sensitized animals than in controls. Preincubation with ICI,
      indomethacin, or pyrilamine alone was unable to inhibit the contractile responses
      to ovalbumin. However, combined administration of ICI, indomethacin and
      pyrilamine completely blocked the responses. CONCLUSIONS: In vivo administration
      of the leukotriene receptor antagonist ICI 198,615 reversed the urodynamic
      changes induced by ovalbumin challenge in sensitized guinea pigs. These results
      indicate that leukotrienes are primarily responsible for the changes in in vivo
      bladder function associated with sensitization.

PMID- 7637092
TI  - Selective type IV collagen defects in the urothelial basement membrane in
      interstitial cystitis.
AB  - PURPOSE: The study sought to identify changes in the urothelial basement membrane
      (UBM) associated with interstitial cystitis (IC). MATERIALS AND METHODS:
      Immunohistochemical assessment of bladder biopsies from IC patients and controls
      was compared with clinical and histologic findings. RESULTS: Selective decreases
      or loss of type IV collagen staining, but not laminin, were found in the UBM of 5
      of 11 IC patients with no change in type IV collagen staining of other bladder
      wall sites. CONCLUSIONS: The loss of type IV collagen may represent a primary or
      secondary event and could alter the UBM's role in permeability, thereby
      contributing to the pathogenesis of IC in the subset of IC patients exhibiting
      this change.

PMID- 7637093
TI  - Effect of pili of Serratia marcescens on superoxide production and phagocytosis
      of human polymorphonuclear leukocytes.
AB  - PURPOSE: To determine the role played by superoxide in renal scar formation
      following renal infection. MATERIALS AND METHODS: The piliation of bacteria was
      assessed for its capacity to interact with human polymorphonuclear leukocytes
      (PMNs). Two recombinant strains having either MS or MR pili of Serratia
      marcescens were constructed. RESULTS: The MS-piliated strain stimulated
      superoxide production of PMNs twice as much as the MR- or nonpiliated strains
      did. The MS-piliated strain was more susceptible to phagocytosis than was the MR-
      or nonpiliated strain. CONCLUSION: These data suggest that the MS-piliated strain
      stimulates superoxide production of PMNs associated with phagocytosis, which
      leads to tissue damage in infected organs.

PMID- 7637094
TI  - Expression of protein kinase C delta gene in germ cells.
AB  - PURPOSE: To investigate the biological functions of protein kinase C delta (PKC
      delta) in spermatogenesis. MATERIALS AND METHODS: We examined PKC delta
      transcript in mouse testis by means of in situ hybridization and Northern
      blotting. RESULTS: In testes of normal mice, signals of PKC delta gene expression
      were detected specifically at the spermatid stage. The PKC delta gene was weakly
      expressed in 8-week-old mice and highly expressed by 12 weeks. However, the
      expression was not detected in testes of germ cell-deficient W/Wv mice even at 12
      weeks. CONCLUSIONS: Protein kinase C delta gene expression may be controlled by
      specific developmental processes and PKC delta may play a role in
      spermatogenesis.

PMID- 7637095
TI  - Expression of muscarinic M3-receptors coupled to inositol phospholipid hydrolysis
      in human detrusor cultured smooth muscle cells.
AB  - PURPOSE: To investigate the effect of muscarinic receptor agonists and
      antagonists on the accumulation of inositol phosphates in cultures of human
      detrusor smooth muscle cells. MATERIALS AND METHODS: Primary explant culture was
      used to derive smooth muscle cell lines from small bladder biopsies. The cells
      were loaded with [3H]-myoinositol, stimulated with muscarinic agonists, and the
      accumulation of [3H]-inositol phosphates was measured by liquid scintillation
      counting. RESULTS: Carbachol (EC50 8.3 microM.), methacholine (EC50 7.5 microM.),
      oxotremorine (EC50 2.5 microM.) and pilocarpine (EC50 8.3 microM.) produced
      concentration-dependent rises in the accumulation of total [3H]-inositol
      phosphates. M1 (pirenzepine), M2 (methoctramine) and M3 (4-DAMP and pf-HHSiD)
      muscarinic receptor antagonists significantly antagonized the response induced by
      a submaximal concentration of carbachol (100 microM.). The apparent pA2 values
      were atropine (9.4), 4-DAMP (9.2), pfHHSid (7.4), pirenzepine (6.9) and
      methoctramine (6.3). CONCLUSIONS: These results indicate that human detrusor
      smooth muscle cells in culture express M3 muscarinic receptors which are linked
      to phosphoinositide hydrolysis.

PMID- 7637096
TI  - This month in investigative urology. Commentary on the renal resistive index.

PMID- 7637097
TI  - The clinical implications of procedural deviations during orchiectomy for
      nonseminomatous testis cancer.
AB  - PURPOSE: The clinical implications of procedural deviations during orchiectomy
      for nonseminomatous testis cancer were evaluated. MATERIALS AND METHODS: A
      retrospective review was done of 78 of 1,708 patients (4.6%) with nonseminomatous
      testis cancer who presented to our university following scrotal violation.
      RESULTS: A total of 56 patients (71.8%) underwent hemi-scrotectomy as part of
      treatment. A tumor was found in 6 of 56 hemi-scrotectomy specimens (10.7%) and 3
      showed local recurrence. Of the 78 patients 5 (6.4%) had local recurrence, while
      1 of 30 (3.3%) with scrotal specimens negative for tumor had recurrence in the
      groin. No patient treated by chemotherapy had local recurrence. CONCLUSIONS:
      Scrotal violation was associated with an increased risk for local recurrence
      mainly when a residual tumor in the scrotectomy specimen was found. The role of
      hemi-scrotectomy to avoid of local or systemic relapse is debatable.

PMID- 7637098
TI  - Crystallization properties in urine from calcium oxalate stone formers.
AB  - PURPOSE: We determine whether stone formers and normal subjects can be
      distinguished in terms of supersaturation with calcium oxalate, and inhibition of
      calcium oxalate growth and aggregation. MATERIALS AND METHODS: An estimate of the
      ion activity product of calcium oxalate was obtained from the analysis of
      calcium, oxalate, citrate and magnesium in 16-hour urine samples obtained between
      6 a.m. and 10 p.m. The inhibition of calcium oxalate crystal growth and
      aggregation was assessed in 8-hour urine specimens obtained between 10 p.m. and 6
      a.m. RESULTS: The ion activity product of calcium oxalate was higher and
      inhibition of crystal aggregation was lower in stone formers than in normal
      subjects. Inhibition of crystal growth was lower only in male stone formers.
      Quotient 1 (10(2) x ion activity product of calcium oxalate/inhibition of crystal
      growth), quotient 2 (10(2) x ion activity product of calcium oxalate/inhibition
      of crystal aggregation) and quotient 3 (10(4) x ion activity product of calcium
      oxalate/[inhibition of crystal growth x inhibition of crystal aggregation]) were
      significantly higher in stone formers. CONCLUSIONS: The biochemical risk
      situation in calcium oxalate stone formers can be summarized by quotient 2 or 3.

PMID- 7637099
TI  - The effect of newer generation lithotripsy upon renal function assessed by
      nuclear scintigraphy.
AB  - PURPOSE: We studied the effect of second generation lithotripsy on renal
      function. MATERIALS AND METHODS: We evaluated 42 patients with unilateral renal
      calculi by nuclear renography, serum creatinine levels, renal ultrasonography and
      plain radiographs. RESULTS: There was no significant change in glomerular
      filtration rate at 1 or 3 months. Split function of the treated kidneys was lower
      at 1 month (mean 47.2%, p = 0.01) and 3 months (47.3%, p = 0.01) than before
      treatment (49.1%). A greater than 5% decrease in split function of the treated
      kidney occurred at 1 month in 6 patients (16.2%) and at 3 months in 3. Of the
      patients 23 (62.2%) were stone-free and 11 had residual fragments less than 4
      mm., with a 19% retreatment rate for an overall success rate of 91.9%.
      CONCLUSIONS: Newer generation lithotriptors may limit renal damage while
      permitting satisfactory treatment of renal calculi.

PMID- 7637100
TI  - Age-related changes in resistive index following extracorporeal shock wave
      lithotripsy.
AB  - PURPOSE: Changes in intrarenal vascular resistance after extracorporeal shock
      wave lithotripsy (ESWL*) were studied with Doppler ultrasound techniques.
      MATERIALS AND METHODS: In 76 patients the resistive index was measured at an
      interlobar artery before and after ESWL in the treated and contralateral kidneys.
      The resistive index levels were compared to N-acetyl-beta-D-glucosaminidase
      levels in 40 patients. RESULTS: We found an age-related positive linear
      correlation between post-therapeutic resistive index increases and patient age. N
      acetyl-beta-D-glucosaminidase levels were also elevated after ESWL but these
      elevations were not age-related. CONCLUSIONS: Elderly patients have a higher risk
      of post-ESWL renal tissue damage.

PMID- 7637101
TI  - The extraperitoneal approach and subcutaneous emphysema are associated with
      greater absorption of carbon dioxide during laparoscopic renal surgery.
AB  - PURPOSE: We investigated the association of carbon dioxide absorption with the
      approach (transperitoneal versus extraperitoneal) and other factors during
      laparoscopy. MATERIALS AND METHODS: Carbon dioxide elimination during
      laparoscopic renal surgery was retrospectively calculated in 63 patients.
      RESULTS: Carbon dioxide elimination increased with time. Multiple factorial
      analysis revealed that subcutaneous emphysema and the extraperitoneal approach
      were independently associated with a greater increase in carbon dioxide
      elimination. Pneumothorax and pneumomediastinum were more common during
      extraperitoneal procedures. CONCLUSIONS: Carbon dioxide absorption during
      laparoscopic renal surgery increases with time, and is greatest in patients
      treated through an extraperitoneal approach and in those with subcutaneous
      emphysema. Nonetheless, with attentive ventilatory management adverse sequelae of
      hypercapnia can be avoided.

PMID- 7637102
TI  - Chromophobe cell renal carcinoma: clinicopathological features of 50 cases.
AB  - PURPOSE: We review the clinicopathological features of chromophobe cell renal
      carcinoma. MATERIALS AND METHODS: Cases were identified by reviewing the
      histology of all renal neoplasms resected between 1977 and 1990. Clinical data
      were obtained by chart review. RESULTS: Of 50 cases a majority (53%) were
      discovered incidentally and most (86%) were stage I. Typical pathological
      findings included the presence of 2 cell types (pale and eosinophilic),
      reactivity for Hale's colloidal iron, ultrastructural cytoplasmic vesicles and
      deoxyribonucleic acid aneuploidy. At last followup 47 patients (94%) were tumor
      free or dead of unrelated causes. Survival was similar in patients with clear
      cell carcinoma of similar grade and stage. CONCLUSIONS: Chromophobe cell
      carcinoma is a morphologically distinctive neoplasm with a favorable prognosis.
      Distinction from renal oncocytoma is important.

PMID- 7637103
TI  - The incidence of multifocal renal cell carcinoma in patients who are candidates
      for partial nephrectomy.
AB  - PURPOSE: A prospective study was performed to determine the incidence of
      multifocal renal cell carcinoma in patients who are candidates for partial
      nephrectomy. MATERIALS AND METHODS: Preoperative imaging studies and surgical
      specimens in 44 patients suitable for partial nephrectomy but undergoing radical
      nephrectomy were prospectively reviewed. RESULTS: Of 44 renal cell cancers 11
      (25%) demonstrated pathological multifocality, while 10 of 11 multifocal tumors
      (91%) occurred in the face of a primary tumor 5 cm. or smaller. Tumor
      multifocality was independent of the size of the primary renal tumor but occurred
      with a slightly higher frequency in tumors of stage T3A or greater even if the
      primary tumor was small. CONCLUSIONS: Partial nephrectomy in patients with
      unilateral renal cancer should be approached with caution and should not be
      performed simply because it is technically feasible.

PMID- 7637104
TI  - Surgical resection for management of renal cancer with hepatic involvement.
AB  - PURPOSE: More than 900 patients who underwent hepatic resections were reviewed to
      identify those whose liver resections were due to involvement by renal cell
      carcinoma. MATERIALS AND METHODS: Three patients with direct hepatic extension of
      the renal cell cancer underwent radical nephrectomy with en bloc partial
      hepatectomy, while 1 with a metachronous recurrence 3 years after nephrectomy
      underwent right triple lobe hepatectomy. There were no postoperative
      complications. RESULTS: Of the en bloc resections 2 showed sarcomatoid features
      on histopathological examination. These patients experienced rapid disease
      progression and died. The remaining 2 patients with typical clear cell carcinoma
      have no evidence of disease. CONCLUSIONS: Experience with these 4 patients has
      demonstrated that hepatic resection is technically feasible and associated with
      acceptable morbidity rates. Surgical management should be considered in patients
      with the uncommon presentation of renal cell carcinoma and localized hepatic
      involvement.

PMID- 7637105
TI  - Laparoscopic nephroureterectomy for upper tract transitional cell cancer: the
      Washington University experience.
AB  - PURPOSE: The recognized form of therapy for patients with ureteral or renal
      pelvis transitional cell carcinoma is total nephroureterectomy with excision of
      the ipsilateral periureteral cuff of bladder mucosa. We report our experience
      with 10 patients who underwent laparoscopic nephroureterectomy for upper tract
      transitional cell carcinoma through July 1994 and compare them to a contemporary
      group of patients undergoing open nephroureterectomy for the same disease.
      MATERIALS AND METHODS: A total of 10 patients undergoing laparoscopic
      nephroureterectomy for upper tract transitional cell carcinoma was evaluated with
      respect to operative time, surgical specimen weight, pathological stage,
      postoperative analgesia requirement, interval to resume normal oral intake,
      postoperative recovery and results of postoperative surveillance. Of the patients
      8 who underwent open surgical nephroureterectomy during a contemporary period for
      the same diagnosis were evaluated for the same parameters and compared to the
      laparoscopic group. RESULTS: Laparoscopic nephroureterectomy averaged twice as
      long as open nephroureterectomy. However, the laparoscopic patients resumed oral
      intake sooner, required less postoperative analgesia and had a shorter hospital
      stay compared to the open surgical group. The laparoscopic nephroureterectomy
      patients returned to normal activities within less than half the time (2.8 versus
      6 weeks) and completely recovered 5 times more rapidly (6 weeks versus 7.4
      months). CONCLUSIONS: Laparoscopic nephroureterectomy is a feasible treatment
      option for patients with upper tract transitional cell carcinoma. However, 2
      major drawbacks to the approach persist, that is the lengthy operative time and
      the need for significant laparoscopic experience on the part of the surgeon.

PMID- 7637106
TI  - The nonrefluxing ileal conduit: a new form of urinary diversion.
AB  - PURPOSE: We describe a variation of the ileal conduit that includes a
      nonrefluxing nipple valve designed to protect the upper urinary tracts. MATERIALS
      AND METHODS: A total of 13 patients underwent urinary diversion with the
      nonrefluxing ileal conduit. The nonrefluxing nipple valve is created by
      intussuscepting the ileum into the conduit. RESULTS: Followup ranged from 3 to 35
      months. No patient demonstrated radiographic deterioration of the upper tracts or
      a clinically significant increase in serum creatinine level during followup.
      CONCLUSIONS: The nonrefluxing ileal conduit appears to be a viable treatment
      option in select patients with neurogenic bladder dysfunction.

PMID- 7637107
TI  - Abdominal reservoirs for continent urinary diversion.
AB  - PURPOSE: Abdominal reservoirs with a continent stoma were constructed. MATERIALS
      AND METHODS: Different types of artificial valves were fashioned. Our original
      modification for construction of the Kock pouch is described. The main principle
      of our suggested version is the embedded and plicated valve, foregoing the
      antireflux afferent loop, with direct ureteral implantation into the reservoir.
      RESULTS: Of 69 patients 7 died in the postoperative period. Continence was
      achieved in 58 of the remaining 62 patients (93.5%). All 7 patients with the
      embedded valve were continent. CONCLUSIONS: The described modifications led to a
      shorter operating time and simplified certain portions of the operation.

PMID- 7637108
TI  - Reconstruction and diversion.

PMID- 7637109
TI  - Electrokinetic studies of urine-urea mixture across bladder membranes.
AB  - PURPOSE: We ascertain the role of urea in urine and its probable effects on the
      polarizable behavior of bladder interfaces. MATERIALS AND METHODS: Urine was
      systematically diluted, keeping overall volume the same. The methodology of
      nonequilibrium thermodynamics was used, which involves measurements of
      hydrodynamic permeability, electro-osmotic permeability, streaming potential and
      streaming currents, respectively. RESULTS: Effective pressure terms (alpha 1) and
      polarizability terms (alpha 2) were computed, making use of higher order
      phenomenological coefficients, and their concentration dependence was examined.
      Abrupt changes in the values of alpha 1 and alpha 2 are supported by trends in
      higher order phenomenological coefficients. CONCLUSIONS: The polarizable behavior
      of the bladder is maintained up to certain concentrations of urea in urine and
      then it undergoes drastic changes. The role of the bladder in situations of
      improper functioning of the liver and diets without protein may provide an
      explanation.

PMID- 7637110
TI  - Impact of a collaborative care approach to radical cystectomy and urinary
      reconstruction.
AB  - PURPOSE: We report the results of a collaborative care program that has been
      developed for radical cystectomy and urinary reconstruction. MATERIALS AND
      METHODS: All patients undergoing surgery after July 1993 were placed on a
      collaborative care pathway and were compared to patients undergoing the same
      procedure before this period. RESULTS: Total adjusted hospital charges decreased
      from $31,174 to $19,479. Hospital stay decreased from 12.7 to 10.3 days. There
      were also decreases in duration of surgery, blood loss, intensive care unit use
      and postoperative morbidity rates. CONCLUSIONS: Collaborative care pathways
      favorably affect the cost efficiency of care and provide favorable surgical
      outcomes.

PMID- 7637111
TI  - Autogenous reconstruction with the lower extremity deep veins: an alternative
      treatment of prosthetic infection after reconstructive surgery for aortoiliac
      disease.
AB  - PURPOSE: This report evaluates the efficiency of use of the lower extremity deep
      vein as arterial conduits in the autogenous repair of prosthetic infection after
      reconstructive aortoiliac surgery. METHODS: We reviewed our records for the
      period 1990 to 1994 of all patients with prosthetic infection after
      reconstruction for aortoiliac disease, and we selected for this study all those
      patients who underwent autograft repair with the lower extremity deep veins.
      RESULTS: Included were 15 patients: 12 had previously undergone direct
      aorto(ilio)femoral reconstruction, and three had an extraanatomic prosthetic
      graft. Thirteen patients were admitted with primary graft infection, and two were
      admitted with secondary graft-enteric erosion. Treatment consisted of prosthetic
      excision and aorto(ilio)femoral reconstruction with the superficial femoral vein.
      In situ reconstruction was performed in 12 cases. The operative mortality rate
      was 7%. There were no early graft occlusions. One patient underwent an above-knee
      amputation because of concomitant femoropopliteal occlusion in the presence of a
      patent deep venous aortofemoral graft. Early postoperative limb swelling was
      common and was controlled with bed rest, elastic stockings, or intermittent
      pneumatic compression. The mean follow-up of this series was 17 months (range 4
      to 33 months). Two patients died of unrelated causes. One graft occluded after 16
      months. There were no reinfections, and all but one patient resumed normal daily
      activities. Disability from removal of the deep veins was minimal: only one
      patient continues to wear elastic stockings for limb swelling and shows signs of
      venous hypertension more than 2 years after surgery. CONCLUSION: Harvesting of
      the lower extremity deep veins is well tolerated. Autogenous reconstruction with
      these veins provides good potential for salvage of life and limbs in case of
      prosthetic infection. A longer period of follow-up is required to study the long
      term behavior of these grafts and to allow definite comparison with more
      conventional approaches.

PMID- 7637112
TI  - Correlation of striatal dopamine release and peripheral hypertension after
      transient ischemia in gerbils.
AB  - PURPOSE: Intracranial norepinephrine release has been associated with post
      carotid endarterectomy hypertension in human beings. To study this phenomenon
      under more controlled conditions, we studied the relationship of cerebral
      catecholamines and blood pressure in gerbils, whose cerebral circulation is
      similar to that in human beings. METHODS: Twelve anesthetized gerbils underwent
      iliac artery blood pressure monitoring and in vivo electrochemistry catecholamine
      monitoring with use of catecholamine-specific electrodes placed stereotactically
      into the cerebral striatum. Six gerbils underwent 10 minutes of bilateral carotid
      artery occlusion (ischemic), whereas six underwent carotid artery dissection
      without occlusion (control). RESULTS: The control group demonstrated a continuous
      gradual decline in blood pressure and striatal catecholamine during the 150
      minute observation period. In contrast the ischemic gerbils demonstrated a sharp
      catecholamine rise during ischemia, a marked catecholamine drop shortly after
      carotid artery unclamping, and then a secondary larger catecholamine release that
      peaks in 60 minutes and gradually returns to baseline in 120 minutes. The blood
      pressure closely followed the catecholamine levels, with a sharp 20 mm Hg rise in
      blood pressure above baseline during carotid artery occlusion, followed by a
      dramatic 10 mm Hg drop below baseline after carotid artery unclamping and then a
      gradual rise of the blood pressure 25 mm Hg above baseline, which peaks in 80
      minutes, with a gradual decline to the same blood pressure as in the control
      subjects 120 minutes after ischemia. CONCLUSION: We conclude that striatal
      catecholamine release correlates with peripheral blood pressure during transient
      cerebral ischemia and reperfusion. This phenomenon may explain the mechanism of
      post-carotid endarterectomy hypertension in human beings, and this gerbil model
      can be used to study its prevention and treatment.

PMID- 7637113
TI  - Graft smooth muscle cells specifically synthesize increased collagen.
AB  - PURPOSE: Anastomotic intimal hyperplasia is characterized by smooth muscle cell
      (SMC) proliferation, but its final form is predominantly extracellular matrix.
      The purpose of this study was to compare collagen synthesis from graft SMC to
      that from adjacent native arterial SMC. METHODS: Thoracoabdominal bypass grafts
      were excised 20 weeks after implantation into canine models. SMC harvested from
      six anastomotic graft segments and adjacent native aorta were passaged twice,
      grown to near-confluence, and then assayed for collagen synthesis and total
      protein synthesis. In four of these sites type I alpha-1 procollagen mRNA levels
      were measured and normalized to glyceraldehyde-3-phosphate dehydrogenase. To
      control for increases in collagen synthesis associated with proliferation, SMC
      were plated at equal densities and tritium-thymidine incorporation and DNA
      concentration were determined. Data (mean +/- SE) were analyzed with two-factor
      ANOVA for repeated measures and paired Student t test and were considered
      significant if p < 0.05. RESULTS: There was no difference in thymidine
      incorporation and total protein synthesis between groups, but collagen synthesis
      (graft: 52.9 +/- 1.6 disintegrations per minute/ng DNA versus native: 42.6 +/-
      1.9 dpm/ng DNA; p = 0.03) and collagen synthesis as a percentage of total protein
      synthesis (graft: 7.16% +/- 0.11% versus native: 5.8% +/- 0.14%; p = 0.001)
      increased significantly in graft SMC as compared to native SMC. Type I alpha-1
      procollagen mRNA levels were higher in graft SMC, but this difference was not
      significant. CONCLUSIONS: Graft SMC specifically produce more collagen than SMC
      from adjacent native artery. This change does not simply reflect increases in
      either total protein synthesis or proliferation and may, in part, be due to
      increased collagen gene expression.

PMID- 7637114
TI  - Venous reflux in symptom-free vascular surgeons.
AB  - PURPOSE: Work posture and occupation are among the most controversial
      predisposing factors associated with venous disease. We examined the distribution
      and extent of venous reflux in the lower extremities of symptom-free vascular
      surgeons, who were typically classified as leading a life of prolonged standing,
      in comparison to a group of symptom-free volunteers. METHODS: In this prospective
      study (January 1991 to April 1994), the venous system in the lower limb veins of
      28 vascular surgeons (56 limbs) and 25 normal volunteers (50 limbs) was examined
      by color-flow duplex imaging. The two groups were matched for age (29 to 45
      years) and sex (all men). Subjects with clinical signs and symptoms of venous
      disease, history of deep or superficial vein thrombosis, or previous venous
      operation or injection sclerotherapy were not included in the study (12 vascular
      surgeons). RESULTS: Venous reflux was detected in 29 limbs of vascular surgeons
      (52%) and in 16 limbs of the control group (32%) (chi-squared test = 4.232, p =
      0.039). In the latter, superficial venous incompetence was detected in 9 of 50
      limbs (18%), deep venous or perforator incompetence in 3 of 50 limbs (6%), and
      venous incompetence involving both the superficial and deep systems in 4 of 50
      limbs (8%). In the group of vascular surgeons, reflux in the superficial veins
      was seen in 22 of 56 limbs (39%), in the deep and or perforating veins in 4 of 56
      limbs (7%), and in both the superficial and deep veins in 3 of 56 limbs (5%).
      Superficial venous reflux was more frequently encountered in the limbs of 45% of
      vascular surgeons (25 of 56) than in the limbs of the control subjects 26% (13 of
      50) (chi-squared test = 3.99, p = 0.047). Distal long saphenous vein reflux alone
      accounted for 39% (5 of 13) of any superficial venous incompetence in the limbs
      of the control subjects, and was higher, at 48% (12/25), in the vascular
      surgeons. Reflux in the gastrocnemial veins was equally distributed between the
      limbs of the control subjects (10%) and the vascular surgeons (11%). CONCLUSIONS:
      Venous reflux was more frequently seen among symptom-free vascular surgeons than
      normal individuals of a nonmedical vocation. The superficial system was by far
      the most common site of venous incompetence in both groups. Below-knee-long
      saphenous vein reflux in any combination was present in more than 75% of the
      limbs with superficial venous incompetence.

PMID- 7637116
TI  - Pancreaticoduodenal artery aneurysm: a case report and review of the literature.
AB  - A case of true pancreaticoduodenal artery (PDA) aneurysm is reported. A calcified
      lesion was initially detected by plain x-ray films, and an essential diagnosis
      was made before operation by intravenous digital subtraction angiography (IVDSA).
      Surgical resection of the aneurysm was performed successfully. Additionally, we
      reviewed a total of 82 cases with PDA aneurysm out of the 88 cases that had been
      reported in the English-language literature up to 1993. Fifty-three cases were
      accompanied by aneurysmal rupture (rupture group), and 29, including our case,
      were without rupture (nonrupture group). Because of the high mortality rate
      (49.1%) in the rupture group, a precise diagnosis and adequate treatment of PDA
      aneurysm before rupture is important. In the nonrupture group, a calcification on
      radiography appeared in 61.6% of the cases in which aneurysms were not found
      incidentally; this seems to be a significant indication for angiography.
      Moreover, intravenous digital subtraction angiography is quite useful for the
      screening of PDA aneurysm because it is an easy and noninvasive examination.

PMID- 7637115
TI  - Increased turnover of collagen in abdominal aortic aneurysms, demonstrated by
      measuring the concentration of the aminoterminal propeptide of type III
      procollagen in peripheral and aortal blood samples.
AB  - PURPOSE: The pathogenesis of abdominal aortic aneurysm (AAA) involves many
      factors; elastin degradation is believed to lead to initial dilation, whereas
      changes in the collagen structure predispose the aneurysm to rupture. The major
      collagens in the aortic wall are types I and III. We set out here to determine
      whether changes in serum propeptide of type III procollagen (PIIINP), a
      biologically relevant marker of type III collagen turnover, could be associated
      with the characteristics of AAA. METHODS: The aminoterminal PIIINP and the
      carboxyterminal propeptide of type I collagen were measured by radioimmunoassay
      in 87 patients with AAA and 90 control subjects with aortodistal
      arteriosclerosis. The samples were taken from the peripheral blood and from the
      abdominal aorta at the levels of the diaphragm and the common iliac artery.
      RESULTS: Mean PIIINP concentrations were higher in patients with AAA than in
      control subjects (3.47 micrograms/L vs 2.73 micrograms/L, p < 0.0001),
      correlating positively with aneurysm diameter in the former (r = 0.27, p = 0.04)
      and with the maximum thickness of the intraluminal thrombus (r = 0.39, p =
      0.003). The gradient in PIIINP between the upper and lower end of the abdominal
      aorta was significant in the AAA group (-0.30 microgram/L, range -0.20 to -0.50
      vs -0.10 micrograms/L, range -0.20 to 0.30, p = 0.002). CONCLUSIONS: These
      studies indicate that the turnover of type III collagen is increased in patients
      with AAA.

PMID- 7637117
TI  - Endoluminal repair of atypical dissecting aneurysm of descending thoracic aorta
      and fusiform aneurysm of the abdominal aorta.
AB  - A 62-year-old male patient was admitted with acute dissociation of the descending
      thoracic aorta and an infrarenal abdominal aortic aneurysm (AAA). Investigation
      revealed that the thoracic dissection probably had arisen retrogradely in the
      posterior wall of the AAA and extended superiorly to the left subclavian artery
      as a blind sac. Implantation of an endoluminal graft device below the renal
      arteries enabled simultaneous treatment of the AAA and the thoracic aortic
      dissection. The patient had an uncomplicated recovery. Postoperative aortography
      and computed tomography demonstrated normal flow through the aorta and endograft
      without leak of contrast into the AAA sac or the false lumen of the dissection.
      Contrast computed tomography 6 months after operation demonstrated that the false
      lumen was no longer evident.

PMID- 7637118
TI  - Dissection of the external iliac artery in highly trained athletes.
AB  - We report a series of four acute external iliac artery dissections occurring in
      three patients within days of completion of ultraendurance athletic events. Acute
      dissection of the external iliac artery in highly trained athletes after
      competition has not been previously documented. A retrospective review of three
      cases was performed with subsequent follow-up, including imaging and hemodynamic
      measurements. Dissection was suspected on the basis of duplex imaging results in
      one case, and arteriography confirmed dissection in all cases. All patients were
      endurance athletes over the age of 40 years. One patient was found to have
      bilateral lesions. Treatment in two cases was initiated with percutaneous
      transluminal angioplasty, one with a successful result and subsequent Plamaz
      stent placement. In the other case percutaneous transluminal angioplasty was
      unsuccessful, and operative repair was required with the placement of a graft.
      The final patient who had bilateral involvement was treated conservatively. At a
      mean follow-up of 32 months, there have been no complications, and all patients
      have normal resting hemodynamics. Follow-up duplex imaging shows healing of the
      dissections in the untreated patient. Histopathologic study in the patient
      treated with operation disclosed dissection in an otherwise normal arterial wall.
      Highly trained athletes over the age of 40 are susceptible to external iliac
      artery dissection, and successful treatment has been achieved by surgical,
      endovascular, and conservative therapies.

PMID- 7637119
TI  - Lower extremity lymphedema caused by acquired immune deficiency syndrome-related
      Kaposi's sarcoma: case report and review of the literature.
AB  - A case of severe lymphedema of the lower extremity caused by obstruction by human
      immunodeficiency virus-associated Kaposi's sarcoma is presented. A review of the
      signs and symptoms of obstructive lymphedema and Kaposi's sarcoma is provided.
      Early recognition of this clinical entity may allow use of simple preventative
      measures and help to avoid this life- and limb-threatening situation.

PMID- 7637121
TI  - Norman Freeman: the "first" American specialist in vascular surgery.

PMID- 7637120
TI  - Late complication of a Greenfield filter associating caudal migration and
      perforation of the abdominal aorta by a ruptured strut.
AB  - We report the case of a 67-year-old woman who was admitted for surgical removal
      of a Greenfield filter that had been inserted 7 years before because of recurrent
      deep vein thrombosis associated with pulmonary embolism. This complication
      appeared on a plain abdominal radiogram that showed a 7 cm distal migration of
      the filter, a 30-degree angulation, and rupture of a strut at the level of the
      hub. Computed tomography, aortography, and ascending cavography demonstrated that
      the inferior vena cava was perforated by the struts and that the ruptured strut
      had penetrated the infrarenal aorta. As demonstrated by scanning electron
      microscopy, the fracture was due to a structural defect of the strut at its
      insertion point within the hub, with no sign of corrosion. Energy-dispersive
      radiography analysis failed to demonstrate impurity in the metal composition.

PMID- 7637122
TI  - Regarding "the brachiocephalic elbow fistula: a useful alternative angioaccess
      for permanent hemodialysis".

PMID- 7637123
TI  - Carotid endarterectomy and local intraarterial thrombolysis: simultaneous
      procedure in acute occlusion of the internal carotid artery and middle cerebral
      artery embolism.

PMID- 7637124
TI  - Simplified suturing of the calcified aorta.

PMID- 7637125
TI  - Endovascular repair of two abdominal aortic aneurysms.

PMID- 7637126
TI  - Probe of heat wave deaths under way.

PMID- 7637127
TI  - Infectious diseases report calls for global control.

PMID- 7637128
TI  - Aging heart adapts to change; researchers begin to unravel some mechanisms
      involved.

PMID- 7637129
TI  - Administration attacks increasing use of marijuana.

PMID- 7637130
TI  - From the Centers for Disease Control and Prevention. Heat-related mortality-
      Chicago, July 1995.

PMID- 7637131
TI  - From the Centers for Disease Control and Prevention. Licensure of inactivated
      hepatitis A vaccine and recommendations for international travelers' use.

PMID- 7637132
TI  - From the Centers for Disease Control and Prevention. Update: recommendations to
      prevent hepatitis B virus transmission--United States.

PMID- 7637133
TI  - From the Centers for Disease Control and Prevention. Acute hepatitis and renal
      failure following ingestion of raw carp gallbladders--Maryland and Pennsylvania,
      1991 and 1994.

PMID- 7637134
TI  - A piece of my mind. Second childhood.

PMID- 7637135
TI  - Managed care: ethical issues.

PMID- 7637136
TI  - Managed care: ethical issues.

PMID- 7637137
TI  - Managed care: ethical issues.

PMID- 7637138
TI  - What component of prenatal care is responsible for improved outcome?

PMID- 7637139
TI  - Dietary therapy in type II diabetes mellitus: correction.

PMID- 7637140
TI  - Ischemic optic neuropathy decompression trial.

PMID- 7637141
TI  - School-based screening for tuberculous infection. A cost-benefit analysis.
AB  - OBJECTIVE: To compare tuberculin screening of all kindergartners and high school
      entrants (screen-all strategy) vs screening limited to high-risk children
      (targeted screening). DESIGN: Decision, cost-effectiveness, and cost-benefit
      analyses. SETTING AND SUBJECTS: Students in a large urban and rural county.
      DEFINITIONS: High risk of tuberculosis infection was defined as birth in a county
      with a high prevalence of tuberculosis. Low risk was defined as birth in the
      United States. OUTCOME MEASURES: Tuberculosis cases prevented for 10, 000
      children screened. Net costs, net cost per case prevented, benefit-cost ratio,
      and incremental cost-effectiveness. RESULTS: The screen-all strategy would
      prevent 14.9 cases per 10,000 children screened; targeted screening would prevent
      84.9 cases per 10,000 children screened. The screen-all strategy is more costly
      than no screening; the benefit-cost ratio is 0.58. Targeted screening would
      result in a net savings; the benefit-cost ratio is 1.2. Screening all children is
      cost saving only if the reactor rate is 20% or greater. The cost per additional
      case prevented for screening all children compared with targeted screening (+34
      666) is more than twice as high as treatment and contact tracing for a case of
      tuberculosis (+16 392). CONCLUSIONS: Targeted screening of schoolchildren is much
      less costly than mass screening and is more efficient in prevention of
      tuberculosis.

PMID- 7637142
TI  - The risk of myocardial infarction associated with antihypertensive drug
      therapies.
AB  - OBJECTIVE: To assess the association between first myocardial infarction and the
      use of antihypertensive agents. DESIGN AND SETTING: We conducted a population
      based case-control study among enrollees of the Group Health Cooperative of Puget
      Sound (GHC). PATIENTS AND METHODS: Cases were hypertensive patients who sustained
      a first fatal or nonfatal myocardial infarction from 1986 through 1993 among
      women and from 1989 through 1993 among men. Controls were a stratified random
      sample of hypertensive GHC enrollees, frequency matched to the cases on age, sex,
      and calendar year. All 623 cases and 2032 controls had pharmacologically treated
      hypertension. Data collection included a review of the ambulatory medical record
      a brief telephone interview of consenting survivors. Antihypertensive therapy was
      assessed using the GHC's computerized pharmacy database. RESULTS: The first
      analysis included only the 335 cases and 1395 controls initially free of
      cardiovascular disease. Compared with users of diuretics alone, the adjusted risk
      ratio of myocardial infarction was increased by about 60% among users of calcium
      channel blockers with or without diuretic (risk ratio = 1.62%; 95% confidence
      interval [Cl], 1.11 to 2.34; P = .01). The second analysis was restricted to 384
      cases and 1108 controls who were taking either a calcium channel blocker or a
      beta-blocker. Among these subjects, the use of calcium channel blockers compared
      with beta-blockers was associated with about a 60% increase in the adjusted risk
      of myocardial infarction (risk ratio = 1.57; 95% Cl, 1.21 to 2.04; P < .001).
      While high doses of beta-blockers were associated with a decreased risk of
      myocardial infarction (trend P = .04), high doses of calcium channel blockers
      were associated with an increased risk (trend P < .01). CONCLUSIONS: In this
      study of hypertensive patients, the use of short-acting calcium channel blockers,
      especially in high doses, was associated with an increased risk of myocardial
      infarction. Ongoing large-scale clinical trials will assess the effect of various
      antihypertensive therapies, including calcium channel blockers, on several
      important cardiovascular end points. Until these results are available, the
      findings of this study support the current guidelines from the Joint National
      Committee on the Detection, Evaluation and Treatment of High Blood Pressure that
      recommend diuretics and beta-blockers as first-line agents unless
      contraindicated, unacceptable, or not tolerated.

PMID- 7637143
TI  - Long-term survival among men with conservatively treated localized prostate
      cancer.
AB  - OBJECTIVE: To determine age-specific, all-cause mortality, disease-specific
      mortality, and life expectancy for men aged 65 to 75 years who are treated only
      with immediate or delayed hormonal therapy for newly diagnosed, clinically
      localized prostate cancer. DESIGN: A population-based, retrospective cohort
      study. SETTING: Patient records were abstracted from 37 acute care hospitals and
      two Veterans Affairs medical centers in Connecticut. Original pathology slides
      were sent to a referee pathologist who was blinded to case outcomes. SUBJECTS:
      All men identified by the Connecticut Tumor Registry with clinically localized
      prostate cancer diagnosed in 1971 to 1976 who were aged 65 to 75 years at the
      time of diagnosis and were untreated or treated with immediate or delayed
      hormonal therapy. MAIN OUTCOME MEASURES: Parametric proportional hazards models
      incorporating tumor histologic findings, comorbidity, and age at the time of
      diagnosis to compare cohort survival with that of men in the general population.
      RESULTS: After a mean follow-up of 15.5 years, the age-adjusted survival for men
      with Gleason score 2 to 4 tumors was not significantly different from that of the
      general population. Maximum estimated lost life expectancy for men with Gleason
      score 5 to 7 tumors was 4 to 5 years and for men with Gleason score 8 to 10
      tumors was 6 to 8 years. Tumor histologic findings and patient comorbidities were
      powerful independent predictors of survival. CONCLUSIONS: Compared with the
      general population, men aged 65 to 75 years with conservatively treated low-grade
      prostate cancer incur no loss of life expectancy. Men with higher-grade tumors
      (Gleason scores 5 to 10) experience a progressively increasing loss of life
      expectancy. Case series reports of survival/mortality experienced by men with
      clinically localized prostate cancer that fail to control for age, tumor
      histologic features, and comorbidities risk significant bias.

PMID- 7637144
TI  - Validity of criteria used for detecting underuse of coronary revascularization.
AB  - OBJECTIVE: To assess criteria used for detecting underuse of coronary artery
      revascularization procedures in terms of patient outcomes. DESIGN: Retrospective
      cohort study using medical records supplemented by a telephone survey and review
      of county death records. SETTING: Four public hospitals and two academically
      affiliated private hospitals in Los Angeles County, California. PARTICIPANTS: A
      total of 671 patients who had coronary angiography between June 1, 1990 and
      September 30, 1991, and who met explicit clinical criteria for the necessity of
      coronary artery bypass graft (CABG) surgery or percutaneous transluminal coronary
      angioplasty (PTCA). MAIN OUTCOME MEASURES: For all patients (n = 671), we
      estimated the association between receipt of necessary revascularization and
      mortality (median follow-up after angiography, 797 days) after adjusting for
      potential confounders. For the patients completing the telephone interview (n =
      374), we examined the relationship between receipt of necessary revascularization
      and frequency of chest pain. RESULTS: Patients who received necessary
      revascularization within 1 year of angiography had lower mortality than those who
      did not (8.7% vs 15.8%, P = .01), and this association persisted after adjustment
      for extent of coronary artery disease, clinical symptom complex, ejection
      fraction, and cardiac surgical risk index (adjusted odds ratio = 0.49; 95%
      confidence interval, 0.28 to 0.86). The same general results were obtained
      whether revascularization was received within 1 year or within 30 days of the
      catheterization, whether panelists' ratings or individual clinical variables were
      entered as covariates, and whether the statistical procedure used was logistic
      regression or Cox proportional hazards analysis. In addition, among patients
      responding to the telephone survey, those receiving necessary revascularization
      had less chest pain at follow-up (P = .03). CONCLUSIONS: Among patients meeting
      criteria for the necessity of revascularization, those receiving a
      revascularization procedure within 1 year had lower mortality than those treated
      medically. These results support the validity of the RAND/UCLA criteria for
      detecting underuse of these procedures, but more research is needed to confirm
      the findings and to determine the validity of guidelines for other procedures.

PMID- 7637145
TI  - The prevalence of nosocomial infection in intensive care units in Europe. Results
      of the European Prevalence of Infection in Intensive Care (EPIC) Study. EPIC
      International Advisory Committee.
AB  - OBJECTIVE: To determine the prevalence of intensive care unit (ICU)-acquired
      infections and the risk factors for these infections, identify the predominant
      infecting organisms, and evaluate the relationship between ICU-acquired infection
      and mortality. DESIGN: A 1-day point-prevalence study. SETTING: Intensive care
      units in 17 countries in Western Europe, excluding coronary care units and
      pediatric and special care infant units. PATIENTS: All patients (> 10 years of
      age) occupying an ICU bed over a 24-hour period. A total of 1417 ICUs provided 10
      038 patient case reports. MAIN OUTCOME MEASURES: Rates of ICU-acquired infection,
      prescription of antimicrobials, resistance patterns of microbiological isolates,
      and potential risk factors for ICU-acquired infection and death. RESULTS: A total
      of 4501 patients (44.8%) were infected, and 2064 (20.6%) had ICU-acquired
      infection. Pneumonia (46.9%), lower respiratory tract infection (17.8%), urinary
      tract infection (17.6%), and bloodstream infection (12%) were the most frequent
      types of ICU infection reported. Most frequently reported micro-organisms were
      Enterobacteriaceae (34.4%), Staphylococcus aureus (30.1%;[60% resistant to
      methicillin], Pseudomonas aeruginosa (28.7%), coagulase-negative staphylococci
      (19.1%), and fungi (17.1%). Seven risk factors for ICU-acquired infection were
      identified: increasing length of ICU stay (> 48 hours), mechanical ventilation,
      diagnosis of trauma, central venous, pulmonary artery, and urinary
      catheterization, and stress ulcer prophylaxis. ICU-acquired pneumonia (odds ratio
      [OR], 1.91; 95% confidence interval[Cl], 1.6 to 2.29), clinical sepsis (OR, 3.50;
      95% Cl, 1.71 to 7.18), and bloodstream infection (OR, 1.73; 95% Cl, 1.25 to 2.41)
      increased the risk of ICU death. CONCLUSIONS: ICU-acquired infection is common
      and often associated with microbiological isolates of resistant organisms. The
      potential effects on outcome emphasize the importance of specific measures for
      infection control in critically ill patients.

PMID- 7637146
TI  - Use of methodological standards in diagnostic test research. Getting better but
      still not good.
AB  - OBJECTIVE: To determine the frequency and temporal changes in application of
      seven accepted methodological standards for the evaluation of diagnostic tests.
      DATA SOURCES: A search of the MEDLINE database yielded 1302 articles about
      diagnostic test studies, during a 16-year secular interval, 1978 through 1993, in
      four prominent general medical journals. STUDY SELECTION: In the 112 eligible
      studies, the test was intended for clinical use, indexes of accuracy (sensitivity
      and specificity or likelihood ratios) were provided, and more than 10 patients
      were enrolled. DATA EXTRACTION: Although each study was critically reviewed by
      one primary observer, a subset was independently evaluated for interrater
      consistency. DATA SYNTHESIS: The percentage of studies that fulfilled criteria
      for each of the seven methodological standards are as follows: (1) specify
      spectrum of evaluated patients, 27%; (2) report test indexes for clinical
      subgroups, 8%; (3) avoid workup bias, 46%; (4) avoid review bias, 38%; (5)
      provide numerical precision for test indexes, 11%; (6) report frequency and
      management of indeterminate results when calculating test indexes, 22%; and (7)
      specify test reproducibility, 23%. Secular increases were found for six of the
      seven standards in ranges of use from 14% to 31% during 1978-1981 to 1990-1993.
      Nevertheless, only one standard, avoidance of workup bias, was fulfilled by more
      than 50% of studies in the most recent secular interval. CONCLUSIONS: These
      results indicate that most diagnostic tests are still inadequately appraised. The
      routine demand for methodological standards could raise the quality of diagnostic
      test information, and the careful predissemination evaluation of diagnostic tests
      could eliminate useless tests before they receive widespread application.

PMID- 7637147
TI  - Universal screening for tuberculosis infection. School's out!

PMID- 7637148
TI  - Calcium channel blockers and myocardial infarction. A hypothesis formulated but
      not yet tested.

PMID- 7637149
TI  - One multimedia medical world. JAMA Review Group.

PMID- 7637150
TI  - Continuous ambulatory esophageal pH monitoring in the evaluation of patients with
      gastroesophageal reflux. Diagnostic and Therapeutic Technology Assessment.
AB  - OBJECTIVE: To provide clinicians with a technology assessment of the safety and
      effectiveness of continuous ambulatory esophageal pH monitoring (CAEpHM) in the
      diagnosis of pathologic gastroesophageal reflux in adults. PARTICIPANTS: A
      literature review and a Diagnostic and Therapeutic Technology Assessment (DATTA)
      survey questionnaire were mailed to 118 physicians with special interest in
      gastroesophageal reflux, esophageal disease, or the use of CAEpHM in the
      diagnosis of noncardiac chest pain. These panelists had been nominated to the
      DATTA panel by appropriate specialty societies and medical schools. A total of 93
      panelists (79%) responded. EVIDENCE: Assessment was based on the expert opinion
      of the panelists, as well as on published scientific and medical literature
      (available as of June 1, 1994). Published studies were identified by a MEDLINE
      search using the terms esophagitis, reflux, and gastroesophageal reflux and by
      review of the references cited in these primary sources. CONSENSUS PROCESS: The
      respondents completed a DATTA survey questionnaire; the survey results were
      tabulated, analyzed, and interpreted by an American Medical Association medical
      scientist. CONCLUSIONS: The safety of CAEpHM was considered to be established in
      adults with chronic heartburn, chronic hoarseness, persistent acid reflux
      refractory to therapy, laryngeal lesions, or noncardiac substernal chest pain.
      The safety of CAEpHM was considered to be promising in adults with episodes of
      apnea. The effectiveness of CAEpHM was considered to be established in adult
      patients with clear primary symptoms that reflect esophageal damage, such as
      chronic heartburn, persistent acid reflux refractory to therapy, or noncardiac
      substernal pain; promising in adults with chronic hoarseness; and investigational
      in adults with episodes of apnea.

PMID- 7637151
TI  - [Portal and peripheral blood immunoreactive insulin concentrations after glucose
      infusion during gastrectomy].
AB  - We evaluated portal and peripheral blood immunoreactive insulin concentrations
      (IRI) after glucose infusion in patients undergoing gastrectomy. Seventy-four
      patients were divided into following two groups: 68 received 25g glucose infusion
      in an hour (glucose group), and the remainder received no glucose (control
      group). Portal blood IRI level in glucose group was about thirty-fold higher than
      that in control group. However, peripheral blood IRI did not correlate with
      portal blood IRI in glucose group. In addition, significant negative correlation
      between portal blood IRI and blood glucose was observed in glucose group. Our
      results reveal that adequate pancreatic insulin secretion occurs after glucose
      infusion during gastrectomy, but peripheral blood IRI does not reflect this
      pancreatic insulin secretion. The results also suggest that blood glucose may be
      regulated by the liver under these conditions.

PMID- 7637152
TI  - [Bupivacaine-fentanyl continuous infusion is superior to morphine bolus injection
      in postoperative epidural analgesia].
AB  - We compared bolus injection of morphine 51 +/- 9 micrograms.kg-1 (M-S group) with
      48 h-continuous infusion of bupivacaine and fentanyl mixture (BF-C group) for
      postoperative epidural analgesia in 100 patients who had undergone upper
      abdominal laparotomy. The epidural analgesia was started about 60 min before
      completion of surgery. The mixed solution, consisting of bupivacaine 48 ml (240
      mg), fentanyl 24 ml (1.2 mg) and 0.9% saline (24 ml), was administered at a rate
      of 2 ml.h-1 by using a 100 ml balloon infuser. Analgesic effects (determined by
      visual analogue scale, verbal pain scores at rest and with movement, additional
      requests of other analgesics), comfort and side effects of the epidural analgesia
      were examined. The evaluation based on postoperative analgesia and comfortable
      feeling rated higher in the BF-C group compared with the M-S group (P < 0.01 to
      of 0.05). There were fewer requests for other postoperative analgesics in the BF
      C group (P < 0.01 to 0.05). There was no significant difference in side effects
      between the two groups. The plasma fentanyl concentration in the BF-C group (n =
      5) was maintained almost constant for the period from 24 to 49 hours after the
      start of infusion and was approximately 1.6 ng.ml-1. We conclude that continuous
      infusion of bupivacaine (2.5 mg.ml-1) and fentanyl (12.5 micrograms.ml-1) at a
      rate of 2 ml.h-1 is superior to bolus injection of morphine for postoperative
      analgesia.

PMID- 7637154
TI  - [Milrinone suppresses TNF-alpha and IL-1 beta release in mouse peritoneal
      macrophages].
AB  - Tumor necrosis factor-alpha (TNF-alpha) exerts a wide spectrum of biological
      activities and contributes to the pathophysiology of septic shock. We studied
      whether milrinone suppresses TNF-alpha and IL-1 beta releases from mouse
      peritoneal macrophages. Mouse peritoneal macrophages were stimulated for 18 hr
      with lipopolysaccharide and different doses of milrinone. TNF-alpha release was
      suppressed in a dose-dependent fashion with milrinone, reaching half-maximal
      inhibition at 30 microM. Release of IL-1 beta was not suppressed with 25 microM
      of milrinone, but it was suppressed with 250 microM of milrinone. We conclude
      that TNF-alpha release is suppressed by therapeutically administered milrinone.

PMID- 7637153
TI  - [Interaction between opiate subtypes and serotonin in suppressing noxiously
      evoked activity of WDR neurons].
AB  - The present study examined interactions between mu and delta opiate subtypes and
      serotonin. Noxious activity evoked by radiant heat (51 degrees C, 8 sec) was
      extracellularly recorded from single discriminated wide dynamic range (WDR)
      neurons in decerebrate spinally transected cats. DAGO (mu selective opioid
      agonist) 1 microgram or DPDPE (delta selective opioid agonist) 30 micrograms was
      combined with serotonin (n = 6 each) 250 micrograms. The dose of each drug by
      itself when administered intrathecally produced no suppression of noxiously
      evoked activity. Although the combination of DAGO and serotonin produced no
      significant suppression of noxiously evoked activity, DPDPE and serotonin
      produced significant suppression to 72.8 +/- 8.0 % (mean +/- SEM) of control
      values (P < 0.01). Intravenously administered naloxone 0.1 mg reversed the
      suppression produced by the DPDPE-serotonin combination. Our results suggest that
      combinations of serotonin and delta selective opiates may be more effective in
      suppressing noxiously evoked activity than combinations with mu selective
      opiates.

PMID- 7637155
TI  - [Effect of sevoflurane and nitrous oxide anesthesia on auditory brainstem
      responses in children].
AB  - The effect of sevoflurane and nitrous oxide anesthesia on the auditory brainstem
      response (ABR) was studied in 70 infants and children ranging in age between 1
      month and 15 years. The latencies in ABR under a non-anesthetic state are no
      longer in the waves originating from the central portion in younger subjects.
      This tendency was recognized under ketamine anesthesia as control and sevoflurane
      and nitrous oxide anesthesia as well. Although nitrous oxide 60% and sevoflurane
      2.5% increased the latency of wave V and the interpeak interval I-V significantly
      in all age groups, the changes were small (0.26 +/- 0.16 msec and 0.23 +/- 0.19
      msec). The changes in infants were relatively large compared with elder subjects.
      These concentrations did not decrease the amplitude of waves I, III and V
      significantly in any age group. Sevoflurane exerted little influence on ABR, and
      it would be useful for ABR testing in children.

PMID- 7637156
TI  - [Effect of amrinone infusion on temperature changes in elderly patients
      undergoing abdominal surgery].
AB  - We evaluated the effect of intravenous infusion of amrinone on the intraoperative
      changes of temperature. Twenty-six elderly patients scheduled for abdominal
      surgery were studied. Temperature was monitored at the rectum and the palm of the
      hand. Fourteen patients in the amrinone group received continuous infusion of
      amrinone from anesthetic induction until the end of operation, while twelve
      patients in the control group received the infusion of normal saline. Peripheral
      temperature was significantly higher in the amrinone group than in the control
      group. Difference between central and peripheral temperature was significantly
      smaller in the amrinone group compared to the control group. It is considered
      that infusion of amrinone is effective to maintain peripheral circulation and to
      keep the peripheral extremities warm in elderly patients undergoing abdominal
      surgery.

PMID- 7637157
TI  - [Effects of oral alpha 2 adrenergic agonists, clonidine and tizanidine, on
      tetracaine spinal anesthesia].
AB  - This study was conducted to evaluate the effects of oral clonidine and
      tizanidine, alpha 2 adrenergic agonists, as premedication for tetracaine spinal
      anesthesia in 63 gynecological patients. The patients were randomly allocated to
      one of six groups. Group 1 (n = 7), group 2 (n = 8) and group 3 (n = 7) received
      13 mg of tetracaine intrathecally in 10 % glucose solution 2.6 ml. Group 4 (n =
      13), group 5 (n = 14) and group 6 (n = 13) received 13 mg of tetracaine
      intrathecally in a volume of 2.6 ml of 10 % glucose solution which contained 0.65
      mg of phenylephrine. As premedication, group 1 and 4 received 0.25 mg of oral
      triazolam; group 2 and 5 received 3 mg of oral tizanidine; group 3 and 6 received
      0.15 mg of oral clonidine. Group 2 and 3, or group 5 and 6 (clonidine or
      tizanidine group, respectively) needed significant longer time for regression of
      Th10 sensory blockade than group 1 or 4 (triazolam). The time for appearance of
      postoperative pain and the time to require postoperative analgesics were longer
      in the groups which had received either clonidine or tizanidine than in the
      groups which had received triazolam. Heart rate and systolic blood pressure in
      group 6 (clonidine-tetracaine-phenylephrine group) showed significant decreases
      (P < 0.05) after the spinal anesthesia. We concluded that oral premedication of
      clonidine and tizanidine prolonged tetracaine spinal anesthesia. From the view
      point of the prolongation of spinal anesthesia and the hemodynamic stability,
      oral premedication with tizanidine seems to be useful.

PMID- 7637158
TI  - [Changes of tympanic temperature by stellate ganglion block].
AB  - The effects of stellate ganglion block (SGB) on the temperature of tympanic
      membrane were determined clinically. Thirty patients received SGB with 8 ml of 1
      % mepivacaine. The tympanic temperature was measured using radiation non-contact
      tympanic membrane thermometer before and after administration of SGB for 30 min
      on the side where SGB was given. Before SGB the tympanic temperature was 37.29 +/
      0.08 degrees C, and there was no difference in the readings between the two
      sides. The tympanic temperature dropped significantly 5 min after SGB and reached
      its lowest value of 36.90 +/- 0.08 degrees C 15 min later. This drop persisted
      for more than 30 min after SGB. The fact that therapeutic effect of SGB is partly
      due to vasodilation and improvement in blood flow to the affected region was
      demonstrated, but these effects in internal carotid arterial system have not yet
      been studied in detail. Tympanic temperature has been proposed as a valid index
      of brain temperature in man. The mechanism of brain cooling has been suggested
      that countercurrent heat exchange takes place between carotid and jugular blood
      flow. Therefore the result of the study suggests that SGB could enhance an
      increase in the brain blood flow.

PMID- 7637159
TI  - [The effects of stellate ganglion block on conjunctival oxygen tension and
      intraocular pressure in patients with retinal vein occlusion].
AB  - We evaluated the effects of stellate ganglion block (SGB) on conjunctival oxygen
      tension, ocular surface temperature (n = 7) and intraocular pressure (n = 18) in
      patients with retinal vein occlusion and other retinopathy. The conjunctival
      oxygen tension (PcjO2) increased from 45.6 +/- 5.0 mmHg to 76.3 +/- 19.9 mmHg in
      45 minutes by SGB and then gradually returned to the control level. PcjO2 120
      minutes following SGB remained still at a higher level compared with the control
      value. Ocular surface temperature increased from 35.1 +/- 0.3 degrees C to 35.9
      +/- 0.3 degrees C 25 minutes following SGB. Intraocular pressure decreased below
      the control level from 15 minutes to 120 minutes by SGB following an initial
      temporary increase. In conclusion, we have found that SGB does increase oxygen
      tension in ocular tissue and decrease IOP.

PMID- 7637160
TI  - [Marked ST segment elevation in ECG during fiberscope-guided nasotracheal
      intubation in a patient with tetanus].
AB  - A patient with tetanus showed marked ST segment elevation in ECG during
      fiberscope-guided nasotracheal intubation. Coronary artery spasm could have been
      induced probably by tetanospasmin and this would lead to transmural ischemia
      during procedure. Pretreatment with anti-hypertensive agents such as calcium
      antagonist as well as sedatives are mandatory even when endotracheal intubation
      without laryngoscope is scheduled in this disease.

PMID- 7637161
TI  - [The effect of flumazenil in reversing midazolam, flunitrazepam or diazepam].
AB  - In 31 adult patients who had undergone spinal or epidural anesthesia, we
      evaluated the effect of flumazenil in reversing midazolam, flunitrazepam or
      diazepam. The patients received midazolam 5 mg, flunitrazepam 1 mg or diazepam 5
      mg 15 min after the spinal or epidural anesthesia. After the completion of
      operation, flumazenil (0.2 mg-1.0 mg) was administered until the patient became
      awake. Blood pressure, pulse rate and respiratory rate before and after
      administration of flumazenil showed no statistically significant changes in these
      groups. There were no significant differences in necessary amount of flumazenil
      among these groups. The time necessary for the patient to be awake in midazolam
      group was significantly shorter than that in flunitrazepam or diazepam group.
      Half of the patients in flunitrazepam and diazepam groups slept again after
      leaving the operating room, but they presented no clinical problems. In
      conclusion, we consider that flumazenil does not affect circulation and
      respiration, so it seems to be safe and effective for reversing benzodiazepins in
      clinical situation.

PMID- 7637162
TI  - [A case of using continuous double-tapped epidural analgesia for herpes zoster
      duplex].
AB  - A 66-year-old woman developed herpes zoster duplex, which is a rare disease. She
      had severe pain at the right upper back area and left lower abdominal area. The
      authors used double-tapped continuous epidural analgesia for this patient. The
      catheters for the epidural block were placed at the 8th thoracic vertebral level
      and 2nd lumbar vertebral level. After the start of continuous epidural block, she
      suffered from nausea, vomited, and felt dizzy. It was evident that these symptoms
      were caused by local anesthetic toxicity. We emphasize that we must pay attention
      to the patient who undergoes continuous double-tapped epidural analgesia for pain
      relief so as not to elicit local anesthetic toxicity.

PMID- 7637163
TI  - [Finding appropriate tube position by the cuff palpation method in children].
AB  - The present study was designed to examine whether palpation of the endotracheal
      tube cuff indicates appropriate positioning in the children. In 59 children, we
      used a cuffed endotracheal tube (3.5-5 mm ID) to measure the distance from the
      carina to the distal tip of the endotracheal tube, when we can palpate the
      endotracheal tube cuff between the cricoid cartilage and the suprasternal notch.
      Following slow induction of anesthesia and muscle relaxation, each patient was
      intubated with a cuffed endotracheal tube of size suitable for age. The cuff was
      inflated with 0.5-1 ml of air, and palpated between the cricoid cartilage and the
      suprasternal notch. The distance between the carina and the tube tip measured by
      a fiberscope was more than 1.0 cm, which is thought to be safe to prevent
      bronchial intubation. The cuff was deflated after measurement. There were no
      complications attributable to use of cuffed endotracheal tubes. We concluded that
      the cuff palpation method was a rapid, reliable and simple technique to ensure
      the proper tube position in children.

PMID- 7637165
TI  - [Non-invasive monitoring of cerebral oxygenation by NIR spectrophotometry
      (clinical trial)].
AB  - A Shimazu OM-100A near infrared spectrophotometer was used to monitor the
      cerebral oxygenated hemoglobin (Oxy-Hb), deoxygenated hemoglobin (Deoxy-Hb) and
      total hemoglobin (Total-Hb) in 3 patients with a) massive hemorrhage, b) ruptured
      aneurysm in the abdominal aorta, or c) hypercapnia. The hematocrit value of the
      patient with massive hemorrhage decreased rapidly to 18 %; the Total-Hb and Oxy
      Hb also decreased significantly. Red blood cell transfusion raised the Oxy-Hb
      level, indicating an improvement in cerebral oxygenation. In the patient with a
      ruptured aneurysm, changes in blood flow brought about by clamping or declamping
      of the abdominal aorta were immediately reflected by corresponding changes in
      Total-Hb and Oxy-Hb. Oxy-Hb increased significantly and correlated well with the
      PETCO2 value in the patient with hypercapnia. Thus, NIR spectrophotometry is a
      useful non-invasive tool which can monitor metabolic and hemodynamic changes in
      the brain in various pathological conditions.

PMID- 7637164
TI  - [The duration of action of vecuronium in five patients after kidney
      transplantation--comparison with that during kidney transplantation].
AB  - We compared the duration of vecuronium action in five patients after the kidney
      transplantation with that during kidney transplantation. After the
      transplantation, three patients required no hemodialysis therapy but two patients
      underwent hemodialysis therapy again. In all these five patients, including
      patients who were back to hemodialysis therapy, the durations of vecuronium
      action after receiving transplanted kidney were shorter than those during kidney
      transplantation. These shortened durations are speculated to be mainly due to
      excretion of vecuronium by the transplanted kidney and the effect of long term
      steroid therapy. However in this study the durations of vecuronium action in
      patients who required further hemodialysis therapy were also shorter than those
      during kidney transplantation. To determine whether this is a common or
      exceptional phenomenon, further evaluation should be needed.

PMID- 7637166
TI  - [A transient sinus arrest after right stellate ganglion block--assessment of
      autonomic function by heart rate spectral analysis].
AB  - We experienced a case of sinus arrest probably induced by right stellate ganglion
      block (SGB). A healthy medical student volunteered in our study of the cardiac
      autonomic nervous system and received the SGB. After the Holter ECG had been
      attached, the SGB was performed with mepivacaine 8 ml. Horner's sign was observed
      after about 3 minutes. A transient (15 s) sinus arrest occurred suddenly after
      about 6 minutes of the tilt test probably due to a vasovagal reflex, and the
      subject lost consciousness. From spectral analysis of the Holter ECG recording,
      the right SGB may be closely involved in the induction of the sinus arrest. Our
      present case suggests that sinus arrest may occur if a patient stands up after
      right SGB.

PMID- 7637167
TI  - [The efficacy of intravenous lidocaine on various types of neuropathic pain].
AB  - We examined the efficacy of systemic local anesthetics on various types of
      neuropathic pain in 89 patients. Lidocaine 1.5 mg.kg-1 was infused intravenously
      for one minute. Pain score (PS) by visual analogue scale (VAS, 0-10) was measured
      1, 5, 15 and 35 min after the infusion. The efficacy of intravenous lidocaine was
      evaluated by PS which was lowest after infusion. PS decreased to less than 50
      percent of pre-infusion value in more than 75 percent of cases of cancer pain,
      postherpetic neuralgia, trigeminal neuralgia, low back pain with signs of root
      pain or spinal canal stenosis, peripheral nerve injury and thalamic pain, in 50
      75 percent of cases of herpetic neuralgia, and in less than 50 percent of cases
      of cervical spondylosis, spinal cord injury, reflex sympathetic dystrophy,
      causalgia and psychogenic pain. This study suggests that systemic local
      anesthetics is effective in neuropathy due to cancer pain, postherpetic
      neuralgia, trigeminal neuralgia, low back pain with signs of root pain or spinal
      canal stenosis, peripheral nerve injury and thalamic pain.

PMID- 7637168
TI  - [Transient tracheal obstruction during surgical correction of scoliosis in a
      patient with Marfan's syndrome].
AB  - A 13-yr-old male with Marfan's syndrome underwent surgical correction of severe
      scoliosis. He had not manifested dyspnea previously in any position. Under
      anesthesia with thiamylal and vecuronium, his trachea was intubated with a
      reinforced endotracheal tube without any difficulty. Anesthesia was maintained
      with nitrous oxide and fentanyl, 8 micrograms.kg-1. The patient was placed in a
      prone position. Thirty min after the start of operation, when orthopedists
      compressed the thoracic vertebrae vertically, positive pressure ventilation
      became impossible abruptly, even with a high airway pressure. Three min later,
      ventilation became possible after cessation of compression and by mouth-to-tube
      insufflation. SpO2 monitored with a pulse oximeter recovered immediately from 61%
      to 99%. A capnogram showed a lengthy retardation of an inspiratory phase.
      Emergency fibreoptic bronchoscopy revealed that the trachea had been compressed
      vertically; the compression was reduced by moving the chest supporters laterally.
      After the apneic episode, the operation continued uneventfully, and he was
      discharged a month later. A severe deformity of the thorax due to severe
      scoliosis and weak tracheal tissue due to connective tissue defect caused partial
      tracheal compression before the surgery, and made his trachea susceptible to
      complete obstruction by vertical external compression on the thorax. Patients
      with Marfan's syndrome and scoliosis should have careful preoperative airway
      evaluation. The selection and positioning of endotracheal tubes should be done
      with care. During surgery, the patient's body position and the condition of the
      trachea should be checked frequently. Capnography and fiberoptic bronchoscopy
      seem to be mandatory for early detection of tracheal stenosis and prevention of
      tracheal obstruction.

PMID- 7637169
TI  - [Perioperative management of patients with Meigs syndrome].
AB  - We report our perioperative management of three cases of Meigs syndrome. The
      major pre-operative problems in Meigs syndrome are physical trouble caused by
      giant mass in peritoneal space, respiratory distress, and poor nutrition. These
      problems must be settled before the operation. The important points in the pre
      operative management are 1) respiratory care employing the intermittent positive
      pressure breathing (IPPB) and the pleural effusion drainage, and 2) the
      correction of intravascular volume and the concentration of albumin and
      hemoglobin by transfusion of massive lactated Ringer solution and albumin
      solution and/or whole blood when they are necessary. During the operation, the
      epidural anesthesia under spontaneous breathing is the best method of anesthesia.
      According to circumstances, we adopt the intra-tracheal intubation with
      continuous positive airway pressure breathing (CPAP). We can generally deal with
      excessive bleeding by transfusion of lactated Ringer solution and plasma
      expander, during the first half of operation. By the end of the operation,
      however, the correction of the concentration of albumin and hemoglobin must be
      made by the fresh frozen plasma and blood transfusion. After the operation, we
      use epidural analgesia to control the postoperative pain. We have succeeded in
      the treatment of three cases of Meigs syndrome owing to our perioperative
      management as described above.

PMID- 7637170
TI  - [Evaluation of preoperative blood preparation and blood consumption for
      implementation of type and screen and maximum surgical blood order schedule].
AB  - We analyzed preoperative blood preparation and intraoperative blood transfusion
      in Kagawa Prefectural Central Hospital and evaluated the effectiveness of maximum
      surgical blood order schedule (MSBOS) and Type and Screen (T&S). Forty seven
      kinds of surgery were performed on 1,283 cases from May, 1991 to April, 1992.
      Transfusion was performed in 179 cases of them. All of 1,884 units of blood that
      had been prepared, were crossmatched and 1,078 of them were actually transfused.
      The Crossmatched to Transfused ratio (C/T ratio) was 1.71. If we adopted MSBOS
      and T&S in 13 elective surgery, 766 units of blood and labour work for
      preoperative blood preparation could have been saved. MSBOS and T&S are
      beneficial for efficient usage of blood transfusion in surgery.

PMID- 7637171
TI  - [Tele-ECG transmission for patients with out-of-hospital cardiac arrest in Osaka
      City].
AB  - The efficacy of a tele-ECG transmission system for transmission of
      electrocardiograms from ambulance to Osaka City University Hospital for 59
      patients with out-of-hospital cardiac arrest was evaluated from December 1992 to
      November 1993. Authorized emergency life saving technicians (ELSTs) transmitted
      electrocardiograms by automobilephone connected with electrocardiogram from the
      location of out-of-hospital cardiac arrest recognized by them to the ICU.
      Successful tele-ECG transfer was achieved in 34 cases (57.6%). The most common
      reason for failure of transmission was interference by large buildings located in
      our urban location, which occurred in 12 of the 25 cases. Defibrillary shock was
      applied in 9 of 10 cases of ventricular fibrillation, and one patient among them
      could return to work. In most cases, laryngeal mask airway insertion was
      performed. The group with tele-ECG transmission required longer time for transfer
      to the hospital. The time required for insertion of the laryngeal mask airway and
      tele-ECG transmission appeared to be the main reason for the delay in transport.
      Although use of tele-ECG transmission can be useful for patients with out-of
      hospital cardiac arrest, further improvement on the transmission system will be
      needed.

PMID- 7637172
TI  - [Brain death committees of university hospitals in Japan].
AB  - We carried out a questionnaire survey on the brain death committees of university
      hospitals in Japan. Fewer than a half of university hospitals have independent
      brain death committees. However, a tendency was observed from this survey that
      the university hospitals established independent brain death committees from the
      pre-existing ethical committees. The role of anesthesiologists seems to become
      more important for decision of the brain death.

PMID- 7637173
TI  - [Unexpected intraoperative respiratory distress; an infant who developed
      tracheomalacia and fatal aortoesophageal fistula due to unrecognized vascular
      ring].
AB  - Vascular rings cause respiratory distress and dysphasia by tracheoesophageal
      compression. We present a case of tracheomalasia and fatal aortoesophageal
      fistula due to unrecognized vascular ring. A 3-month-old (7.3 kg) boy underwent V
      P shunt operation under sevoflurane anesthesia. The trachea was intubated easily
      using vecuronium with a relatively large-size tube with a diameter of 4.5 mm,
      because of leakage. Gastric intubation was difficult. During scrubbing of the
      head, an asthma-like respiratory distress suddenly occurred. The condition
      responded poorly to ventilatory support and pharmacological interventions.
      Although intraoperative fiberscopy through the tracheal tube and chest X-ray
      showed no tracheobroncheal abnormality, postoperative fiberscopy revealed a
      tracheomalacia. Adequate ventilation was possible only when the tip of the
      tracheal tube was located between the stenotic part and the tracheal carina. On
      the 9th postoperative day, during respiratory management with a tracheal tube,
      fatal esophageal hemorrhage broke out. Postmortern examination revealed a double
      aortic arch with tracheal stenosis and aortoesophageal fistula. The nasogastric
      tube may have led to fistula formation by compression of the esophageal wall
      against an anomalous vessel. When anesthetists encounter an infantile respiratory
      distress, even in perioperative period, vascular rings should be taken into
      consideration.

PMID- 7637174
TI  - [Effect of ulinastatin on the free radical during cardiopulmonary bypass].
AB  - Cardiopulmonary bypass (CPB) involves many factors for generating free radicals.
      It is difficult to detect free radical directly in clinical situations. Vitamin E
      is recognized as an intrinsic radical scavenger. We examined the change of
      vitamin E level to prove indirectly the evidence of free radical generation
      during CPB. Moreover, we investigated the effect of ulinastatin on the free
      radical during CPB by determining the vitamin E level. Twenty patients who
      received cardiac surgery were divided into the membrane oxygenator group and the
      bubble oxygenator group. In each group, five patients received 12,000 units.kg-1
      of ulinastatin 15 min after starting CPB. Blood samples were obtained 15 min
      after starting CPB and 15 min after reperfusion of coronary artery. In the bubble
      oxygenator group without ulinastatin, vitamin E level at reperfusion phase
      decreased significantly compared with that at the start of CPB. In the bubble
      oxygenator group with ulinastatin, vitamin E level at reperfusion phase showed no
      decrease compared with the level at the start of CPB. In the membrane oxygenator
      group, there was no significant change in vitamin E level. Therefore, we suspect
      that a decrease of vitamin E during CPB with bubble oxygenator demonstrates the
      evidence of free radical generation and these results suggest that ulinastatin
      may scavenge free radicals during CPB.

PMID- 7637175
TI  - [Anesthetic management for bronchofiberscopy and esophageal mannometric study in
      a patient with CHARGE association].
AB  - Bronchofiberscopy and esophageal mannometric study were scheduled for a CHARGE
      association patient who complained respiratory distress and dysphagea after PDA
      ligation. We carried out both tracheal intubation and LMA insertion twice. LMA
      insertion was performed smoothly, but mask holding and tracheal intubation were
      very difficult. CHARGE association is a rare multiple anomaly, and presents some
      problems for anesthetic management. Especially, we have to consider the difficult
      airway management in such a patient.

PMID- 7637176
TI  - [Continuous epidural droperidol for postoperative pain].
AB  - We investigated the proper dosage of droperidol continuously infused into the
      epidural space. Sixty patients who received continuous epidural infusion of
      buprenorphine for 24 hours were divided into four groups (Group I: only
      buprenorphine, Group II: 1.25 mg of droperidol added to buprenorphine, Group III:
      2.5 mg of droperidol added to buprenorphine, Group IV: 5 mg of droperidol added
      to buprenorphine). No significant difference was observed in prevention of nausea
      and vomiting among 4 groups. But in group II, III and IV, there was a tendency of
      increased analgesic effects of buprenorphine. Especially in group III, the pain
      level was significantly lower and number of doses of bupivacaine was
      significantly fewer than in group I. In conclusion, droperidol 2.5 mg
      continuously infused into epidural space increases analgesic effects of
      buprenorphine.

PMID- 7637177
TI  - [Statistical analysis of anesthesiologists' thinking patterns concerning
      regulation of the blood pressure and the concentration of inhaled anesthetics].
AB  - During surgery, the anesthesiologists adjust the concentration of inhaled
      anesthetics according to the change in blood pressure in order to achieve good
      control of anesthesia. Usually the thinking patterns of individual
      anesthesiologists differ from one to another. We obtained data from each
      anesthesiologist's thinking pattern concerning the regulation of blood pressure
      and the concentration of inhalational anesthesia. These patterns were analyzed
      statistically and compared for individual anesthesiologist. The results showed
      that anesthesiologists' regulation rules were formed independently of the 3 drugs
      and were specific to individuals. Some trends depending on institution were
      observed, but no statistically significant difference was found.

PMID- 7637178
TI  - [The usefulness of monitoring hepatic venous saturation during open heart surgery
      for a patient with severe liver dysfunction].
AB  - We report the usefulness of monitoring hepatic venous saturation (ShVO2) during
      open heart surgery for a patient with severe liver dysfunction. The patient was a
      55-year-old man who had been suffering from acute aortic regurgitation due to
      bacterial endocarditis. Indocyanine green retention test at 15 min was 55%. Serum
      GOT, GPT and T bilirubin were 56 U.l-1, 35 U.l-1 and 1.5 mg.dl-1 respectively.
      Aortic valve replacement was scheduled in spite of severe liver dysfunction
      because amelioration of congestive heart failure after the operation was expected
      to improve liver dysfunction to the previous chronic state. Anesthesia was
      induced and maintained by intermittent administration of diazepam and low dose of
      fentanyl with 100% oxygen. After induction, we inserted a balloon tipped
      pulmonary catheter with ultra-red beam into hepatic vein by fluoroscopy guidance
      and monitored ShVO2 as an index of hepatic oxygen supply/demand balance. During
      re-insertion of a thoracic catheter, we could detect the continued decrease in
      hepatic vein saturation even after the improvement of systemic circulatory state.
      Postoperatively, liver function became slightly worse for a short period and
      improved thereafter. These results suggest that ShVO2 monitoring is clinically
      useful in detecting hepatic oxygen supply/demand imbalance which circulatory
      monitoring could not uncover during open heart surgery.

PMID- 7637180
TI  - [A patient-controlled analgesia system using a disposable balloon catheter, a PCA
      polyethylene reservoir and a one-way umbrella check valve].
AB  - A disposable continuous infuser with differently sized balloon pressure sources
      (20 ml-3 hr, 40 ml-12 hr and 40 ml-24 hr) with a pressure of approximately 100
      mmHg (DIB international Co., Ltd., Tokyo), is connected to a PCA polyethylene
      reservoir using a Y-connector. Capacity variations of the reservoir are 1 ml
      (assuming subcutaneous dose), 3 ml (intravenous dose) and 5 ml (epidural dose or
      peroral dose). The other opening of the Y-connector is equipped with a one-way
      umbrella check valve (opening pressure, 320-370 mmHg) to prevent the analgesic
      solution from flowing medially unless the PCA polyethylene reservoir is pressed.
      By this system, various target lock-out times can be obtained by varying the type
      of disposable infusor. The target amount of on-demand doses is obtained by
      varying the capacity of the PCA polyethylene reservoir.

PMID- 7637179
TI  - [Usefulness of monitoring with near infrared spectroscopy during retrograde
      cerebral perfusion].
AB  - Recently retrograde cerebral perfusion (RCP), a newly developed technique for
      cerebral protection during surgical replacement for thoracic aortic aneurysm, has
      been used in many institutes. However, there is no established monitoring methods
      for cerebral oxygenation during this procedure. In the present study, we examined
      if near infrared spectroscopy (NIR) is useful for monitoring cerebral oxygenation
      during RCP. We studied 7 patients undergoing operations for aneurysms of the
      ascending aorta and transverse arch in the supine position (Group A) and another
      seven patients undergoing operations for aneurysms of the transverse arch and
      descending aorta in the lateral decubitus position (Group D) in this study and
      monitored cerebral oxygenation with NIR. NIR showed a slow but continuous
      decrease in oxygenated hemoglobin and an increase in deoxygenated hemoglobin
      during RCP, while these changes disappeared following the termination of RCP. The
      degree of these changes in Group D was significantly greater than that in Group
      A. In comparison, we observed rapid reduction of oxygenated hemoglobin during the
      period of circulatory arrest and low perfusion pressure with NIR, suggesting the
      usefulness of RCP for cerebral oxygenation. NIR may be a useful method of
      monitoring cerebral oxygenation during RCP.

PMID- 7637181
TI  - [Air pollution by sevoflurane in operating room and serum and urine inorganic
      fluoride of anesthetists].
AB  - Since lower blood-gas partition coefficient of sevoflurane provides rapid
      induction and emergence from anesthesia, sevoflurane has been used widely for
      inhalational anesthesia. However, because higher minimum alveolar concentration
      of sevoflurane requires a large dosage of anesthetic than other volatile
      anesthetics, air pollution with sevoflurane in the operating room might be of
      great concern. Anesthetists may keep inhaling the low concentration of
      anesthetics every day, even though scavenging system is equipped in the operating
      room. The purpose of this study is to evaluate the effects on anesthetists of the
      low concentration of anesthetics by measuring the inorganic fluoride
      concentration in the urine and serum of anesthetists and operating room nurses.
      Healthy 29 anesthesiologists and two operating room nurses were studied. Informed
      consent was obtained. Inorganic fluoride ions in the serum and urine were
      measured. Simultaneously sevoflurane concentration in operating room was measured
      in three operating rooms, at two places in the corridor and in the recovery room.
      Sevoflurane concentrations in three operating rooms were 1.22 ppm, 2.13 ppm and
      6.05 ppm respectively. Concentration in the recovery room was 0.544 ppm. Serum
      and urine concentrations of inorganic fluoride were 1.1 +/- 0.1 mumol.l-1 and
      36.2 +/- 17.1 mumol.l-1, respectively (mean +/- SD). Serum concentration of
      inorganic fluoride was within normal ranges. Although it is possible that
      fluoride concentration in urine is influenced by urine volume and a half of
      fluoride deposits in bone, no abnormal values in urine were found in this study.
      These results suggest that long term exposure to low concentration of sevoflurane
      and isoflurane causes no significant increase in their metabolites in operating
      room staffs.

PMID- 7637182
TI  - [Effects of arterial carbon dioxide (PaCO2 not equal to 60 mmHg) on regional
      myocardial tissue oxygen tension and metabolism].
AB  - We investigated the effects of increased arterial carbon dioxide (PaCO2 not equal
      to 60 mmHg) on myocardial tissue oxygen tension and metabolism in anesthetized
      dogs. Ten adult mongrel dogs weighing 15.3 +/- 4.1 kg were anesthetized with 0.5%
      isoflurane in 50% oxygen and ventilated mechanically to maintain normocapnia.
      After thoracotomy, regional myocardial tissue PO2 was measured using a monopolar
      polarographic needle electrode inserted in the myocardium. Electromagnetic blood
      flow probes were applied on the left anterior descending artery and the
      circumflex artery. A 23-gauge catheter was inserted into a coronary vein to
      obtain coronary venous blood for measuring oxygen content, lactate and pyruvate.
      After control normocapnic ventilation, hypercapnia (PaCO2 62.7 +/- 3.2 mmHg) was
      induced by adding 10% carbon dioxide to the inspired gas for 20 minutes. As a
      result, the coronary blood flow and myocardial oxygen tension increased during
      hypercapnia. The myocardial lactate extraction and coronary venous lactate were
      unchanged and excess lactate was kept below zero, although coronary venous L/P
      ratio increased during hypercapnia. These results indicate that hypercapnia
      (PaCO2 not equal to 60 mmHg) increases coronary blood flow and myocardial oxygen
      tension, while myocardial aerobic metabolism is not impaired under hypercapnia.

PMID- 7637183
TI  - [Effects of stellate ganglion block on coronary circulation during acute coronary
      occlusion].
AB  - To evaluate effects of stellate ganglion block (SGB) on coronary circulation
      under coronary occlusion, the changes in cardiac function and tissue blood flow
      in the myocardial ischemic area after right and left SGB were observed in the
      dogs. Tissue blood flow in the myocardial ischemic area measured with laser
      doppler flowmeter showed no significant change after right or left SGB. In the
      right SGB group, heart rate, circumflex branch blood flow and rate pressure
      product decreased significantly (P < 0.01); end-diastolic pressure increased
      slightly (P < 0.05); myocardial oxygen extraction rate showed no significant
      change. On the other hand, in the left SGB group, heart rate, circumflex branch
      blood flow and rate pressure product showed no significant changes, while end
      diastolic pressure and myocardial oxygen extraction rate increased significantly
      (P < 0.05). These data suggest that although right SGB might be useful to improve
      the oxygen demand-supply relation, left SGB does not improve the oxygen demand
      supply relation and might increase the risk of myocardial ischemia.

PMID- 7637184
TI  - [Effects of nitroglycerin, prostaglandin E1, trimetaphan and nicardipine on
      systemic vascular resistance, pulmonary vascular resistance and pulmonary
      systemic vascular resistance ratio in dogs].
AB  - Effects of the experimentally induced hypotension with 4 vasodilators;
      nitroglycerin (TNG), prostaglandin E1 (PGE1), trimetaphan (TMP) and nicardipine
      (NCP) on systemic vascular resistance (SVR), pulmonary vascular resistance (PVR)
      and pulmonary-systemic vascular resistance ratio (PVR/SVR ratio) were studied in
      dogs. The SVR values were significantly reduced by TNG, PGE1 and NCP, and not
      affected by TMP. The PVR values were significantly reduced by TNG and PGE1, and
      not affected by TMP and NCP. The PVR/SVR ratio values were significantly reduced
      by TNG, and significantly increased by NCP, and not affected by PGE1 and TMP. We
      concluded that TNG reduced PVR and SVR but it affected PVR more; PGE1 reduced PVR
      and SVR equivalently; TMP did not affect PVR and SVR remarkably; NCP reduced SVR
      but did not affect PVR.

PMID- 7637185
TI  - [The effect of dopamine and prostaglandin E1 on urine oxygen tension (PuO2)].
AB  - We reported that PuO2 reflects renal medullary perfusion and decreases during N2O
      O2 isoflurane (GOI) or sevoflurane (GOS) anesthesia. In the present study, we
      examined the effect of dopamine (DOA) or prostaglandin E1 (PGE1) on PuO2 during
      GOI anesthesia. Twenty four patients from elective surgery with GOI anesthesia
      were randomly divided into three groups, i.e. control group (n = 8), DOA group (n
      = 8) and PGE1 group (n = 8). PuO2 decreased significantly in the control group,
      while in the DOA and PGE1 groups, PuO2 was unchanged. These results suggest that
      DOA and PGE1 maintain renal medullary perfusion under GOI anesthesia.

PMID- 7637186
TI  - [Influence of hypotensive anesthesia on the organ blood flow--comparison of
      trinitroglycerine and nicardipine].
AB  - Adult mongrel dogs under anesthesia with 50% N2O + 0.5% halothane were further
      subjected to hypotensive anesthesia. For hypotensive anesthesia, we used two
      different drugs: trinitroglycerine (TNG-group) and nicardipine (NIC-group). In
      each of these groups, we measured respiratory and circulatory parameters and
      organ blood flow. The parameters of organ blood flow measured were renal cortical
      blood flow (RCBF), renal medullarly blood flow (RMBF), liver blood flow (LBF) and
      muscle blood flow (MBF). At the same time, distribution of organ blood flow was
      also determined. In TNG-group, significant decreases were observed in CI, LV
      dp/dt max, MPAP and PCWP due to decrease in venous return. In NIC-group, CI and
      LV dp/dt max increased significantly. No significant changes were seen in PaO2 in
      both groups. During hypotensive anesthesia organ blood flow decreased in all
      sites in TNG-group. However, as to blood distribution rate in TNG-group, RCBF and
      RMBF increased significantly, while a decreasing tendency was seen in MBF. On the
      other hand, in NIC-group RCBF decreased significantly, while MBF increased
      significantly. In NIC-group, distribution rate of RCBF, RMBF and LBF decreased
      significantly, but MBF showed a tendency to increase. From these results, it was
      indicated that hypotensive anesthesia using NIC may be associated with increased
      bleeding from the operative field due to increase in MBF.

PMID- 7637187
TI  - [The effect of isoflurane on the secretion of TNF-alpha and IL-1 beta from LPS
      stimulated human peripheral blood monocytes].
AB  - The cytokines such as tumor necrosis factor and interleukin-1 secreted from
      macrophages/monocytes proved to play important roles in the pathogenesis of
      endotoxemia, severe pancreatitis and other surgical injuries. However, it is
      still unclear how inhalational anesthetic agents influence the secretion of these
      cytokines from macrophages/monocytes. We investigated the effects of isoflurane
      on TNF-alpha and IL-1 beta secretions from human peripheral blood monocytes
      stimulated by lipopolysaccharide. TNF-alpha and IL-1 beta secretions increased
      after LPS stimulation and this increase was inhibited by isoflurane in dose
      dependent fashion. The inhibitory action of isoflurane disappeared between 1 and
      3 hours after stopping isoflurane inhalation. We concluded that isoflurane could
      inhibit TNF-alpha and IL-1 beta secretions from peripheral blood monocytes
      stimulated by LPS in a dose-dependent fashion and that the inhibitory action of
      isoflurane was reversible.

PMID- 7637189
TI  - [Influence of stellate ganglion block on respiratory system].
AB  - The purpose of this study was to investigate the influence of a stellate ganglion
      block (SGB) or stellate ganglion electrical stimulation (SGES) on pulmonary
      resistance, on blood flows of the bronchial, pulmonary and common carotid
      arteries, and on arterial blood gases. Thirteen mongrel dogs were divided into
      two groups; a SGB group (n = 8) and a SGES group (n = 5). Anesthesia was induced
      with pentobarbital 25 mg.kg-1 and the animals were mechanically ventilated to
      maintain constant PaO2 (90-100 mmHg) and PaCO2 (35-40 mmHg). After a thoracotomy,
      the SGB with 0.5% mepivacaine 1.5 ml was performed, or the SGES was performed at
      a strength of 12 volts, and at a frequency of 50 Hz, applied for 30 min. In the
      SGB group, pulmonary resistance after the block did not significantly differ from
      the control. No significant change occurred in blood flows of the bronchial and
      pulmonary arteries, but the common carotid artery flow increased significantly
      after the SGB. Arterial blood gases did not change significantly after the SGB.
      In the SGES group, pulmonary resistance after the stimulation did not
      significantly differ from the pre-value. However, blood flows of the bronchial,
      pulmonary and common carotid arteries decreased significantly after the SGES.
      Arterial blood gases did not change significantly after the SGES. These results
      suggest that the SGB may not influence the respiratory system under normal
      conditions.

PMID- 7637188
TI  - [Portal blood immunoreactive insulin concentration after glucose infusion in
      elderly patients during gastrectomy compared with younger patients].
AB  - We evaluated the effect of aging on portal blood immunoreactive insulin
      concentration, AKBR, and keton body concentration (acetoacetate + beta
      hydroxybutyrate) after glucose infusion (25 g glucose in an hour) in patients
      undergoing gastrectomy. Twenty-seven patients studied were elderly (above 65
      years) and twenty-eight were younger (below 60 years). There was no significant
      difference in portal blood immunoreactive insulin concentration after glucose
      infusion between the two groups of patients. In elderly patients, however, AKBR
      was significantly lower and keton body concentration was significantly higher
      than those in younger patients, and these imply that suppression of ketogenesis
      and activation of hepatic mitochondrial function due to insulin may be reduced in
      elderly patients. These findings suggest that, during gastrectomy, pancreatic
      insulin secretion may not be impaired in elderly patients, but insulin action may
      be attenuated with aging.

PMID- 7637190
TI  - [The effect of nicorandil on the neuromuscular block induced by vecuronium].
AB  - The effect of nicorandil on the neuromuscular block induced by vecuronium was
      investigated in vitro with rat phrenic nerve-hemidiaphragm preparation. Both
      single twitch (ST) and train-of-four ratio (TOFR) elicited with indirect
      electrical stimulation were used. The administration of nicorandil alone showed
      no effects on ST and TOFR. The pre-administration of nicorandil exerted
      significant depressing effect on ST compared with vecuronium alone. High
      concentration of nicorandil (4 x 10(-6) M) produced more significant effect on ST
      compared with low concentration of nicorandil (10(-7) M). In this study, the
      nicorandil showed similar effect as calcium antagonists on neuromuscular
      blockade.

PMID- 7637192
TI  - [Changes in analgesic levels, plasma concentrations and epidurogram during long
      term continuous epidural block].
AB  - The change of analgesic levels, plasma concentrations and the radiographical
      changes of epidural space due to continuous epidural block were studied in 54
      patients receiving pain relief. All the patients received 2 ml per hour of 2%
      lidocaine or 0.5% bupivacaine via the catheter over two weeks. The effect of
      epidural block was determined on 1, 2, 4, 7, 10 and 14 days, the epidurogram was
      performed on 1, 7, 14 days, and plasma concentration of lidocaine or bupivacaine
      was measured on 1, 3, 7, 14 days. We removed catheters in 8 patients because of
      infection around the catheter, pain in the back during injection, the leakage of
      anesthetics, and spontaneous removal. The effects and plasma concentrations of
      epidural block decreased significantly after a week, and the mean segmental
      number of radiographic spread decreased significantly after two weeks. The
      decreasing effect or duration of epidural block was due to decrease in spread of
      anesthetics because of adhesion around the catheter in the epidural space. We
      conclude that the safety period of continuous epidural block is within 2 weeks.

PMID- 7637191
TI  - [Augmentation by succinylcholine of the neuromuscular blocking effect of
      vecuronium in children].
AB  - To evaluate the influence of succinylcholine (Scc) on the neuromuscular blocking
      effect of subsequently administered vecuronium in children, 30 patients aged 2-14
      years scheduled for elective surgery were studied after obtaining the informed
      consent from the parents. Anesthesia was induced with inhalation of sevoflurane,
      nitrous oxide and oxygen. T1 of the adductor pollicis muscle to ulnar nerve
      stimulation elicited by train of four stimulation at 2 Hz was monitored
      continuously by an acceleration transducer. The patients were divided into two
      groups; group V (16 patients) received vecuronium (0.03 mg.kg-1) and group SV (14
      patients) received vecuronium (0.03 mg.kg-1) after 100% recovery of twitch from
      neuromuscular blockade induced with Scc (1.0 mg.kg-1). Short onset of action and
      potentiation of maximal block were demonstrated in group SV. After vecuronium
      administration, a complete suppression of T1 was observed in 8 patients of group
      SV and only 1 patient of group V. The present study demonstrates that the
      neuromuscular blockade of vecuronium can be potentiated with the prior
      administration of Scc in pediatric patients.

PMID- 7637193
TI  - [Synergism of ciprofloxacin and roxithromycin to Pseudomonas aeruginosa biofilm].
AB  - Synergism of ciprofloxacin (CPFX) and roxithromycin (RXM) to bacterial biofilms
      formed by Pseudomonas aeruginosa was investigated. Measurement of antibacterial
      activities and morphological observation with a scanning electron-microscope
      suggested that RXM eradicated the biofilms by unknown mechanism and thereby
      enhanced the bactericidal activity of CPFX to P. aeruginosa in biofilms.

PMID- 7637194
TI  - [Antibacterial activities of cefmenoxime against recent fresh clinical isolates
      from patients in sinusitis].
AB  - In order to evaluate antimicrobial activity of cefmenoxime (CMX), minimum
      inhibitory concentrations (MICs) of CMX and control drugs were determined against
      clinical isolates from patients of sinusitis that were obtained in our laboratory
      from October of 1993 to March of 1994. The results are summarized as follows; 1.
      CMX showed strong antimicrobial activities against Streptococcus pneumoniae,
      Haemophilus influenzae and Moraxella subgenus Branhamella catarrhalis that were 3
      major aerobic bacteria from sinusitis. Antimicrobial activities of CMX against
      benzylpenicillin (PCG)-insensitive S. pneumoniae (PISP) and PCG-resistant S.
      pneumoniae (PRSP) were stronger than those of ampicillin (ABPC), and these strong
      activities suggested that CMX might have strong antimicrobial activities against
      beta-lactamase producing H. influenzae and M. (B.) catarrhalis. 2. Antimicrobial
      activities of CMX against microaerophiles, Streptococcus constellatus,
      Streptococcus intermedius and Gemella morbillorum and against Peptostreptococcus
      spp., from chronic sinusitis and odontogenic maxillary sinusitis, were stronger
      than those of most of the control drugs. 3. The MIC90's of CMX against isolates
      from patients of sinusitis were < or = 0.025-0.39 micrograms/ml. These values
      were lower than transitional concentrations in mucous membrane of maxillary sinus
      obtained when "1% CMX nasal solution" was used with nebulizer. It appears likely
      that sufficient concentrations exceeding MICs against main organisms would be
      obtained by nebulizer treatment using CMX nasal solution.

PMID- 7637195
TI  - [Microbiological assay method for T-3761 concentration in body fluids].
AB  - A microbiological assay method for measurement of T-3761 and its stability in
      body fluids were investigated. The paper disc method proved suitable for this
      assay using Escherichia coli Kp as a test organism and commercially available
      heart infusion agar as a test medium. When using the paper disc method, lower
      detection limit of T-3761 was approximately 0.05 microgram/ml and 0.1
      microgram/ml for 1/15M phosphate buffer (pH 7.0) and human serum, respectively. T
      3761 in human serum and urine was stable under freezing -20 degrees C for at
      least 28 days.

PMID- 7637196
TI  - [Determination of T-3761 in body fluids by high-performance liquid
      chromatography].
AB  - A high-performance liquid chromatographic procedure was developed for
      determination of T-3761 in human serum and urine. The method was based on column
      switching for serum, and direct injection for urine. The peaks were monitored by
      ultraviolet detection. The calibration curve was linear and quantitative in the
      concentration range of 0.01-30 micrograms/ml for serum and 0.5-900 micrograms/ml
      for urine. The intra-assay coefficient of variation was less than 7%. The intra
      day and inter-day coefficient of variation were less than 4%.

PMID- 7637197
TI  - [Absorption, distribution, metabolism and excretion of T-3761, a new quinolone
      derivative, in experimental animals].
AB  - We studied the absorption, distribution, metabolism and excretion of T-3761, a
      new quinolone derivative, in experimental animals. The following results were
      obtained. 1. The peak serum levels of T-3761 after a single oral administration
      to various fasting animals at a dose of 5 mg/kg were high in the order of rats,
      dogs, mice and rabbits, showing favorable absorption in all animals except for
      rabbits. In mice and rats, T-3761 showed higher peak serum levels than ofloxacin
      and ciprofloxacin but T-3761 were more rapidly eliminated from serum than
      ofloxacin and ciprofloxacin. 2. Tissue concentrations of T-3761 in rats were
      similar to those of ofloxacin but its ratio of tissue to serum levels were lower
      than those of ofloxacin. 3. Urinary excretion of T-3761 as active form until 24
      hours after oral administration was 27.3%, 63.1%, 41.0% and 63.3% in mice, rats,
      rabbits and dogs, respectively. Only unchanged T-3761 was detected as active form
      in urine of all animals tested. In rats, urinary concentrations until 2 hours
      after administration were higher than those of ofloxacin. 4. Biliary excretion of
      T-3761 in mice and rats were 2.9% and 1.4% as active form. 5. The absorption of T
      3761 was not different in male and female rats or 8 and 14 weeks old rats. The
      meal lowered absorption of T-3761 in rats. There was no significant difference in
      serum levels, urinary excretion and distribution to tissues after multiple
      administration of T-3761 comparing with its single administration. 6. In rats
      with liver dysfunction induced by D-galactosamine, the serum levels and urinary
      excretion were slightly higher than in normal rats. On the other hands, in rats
      with kidney dysfunction induced by HgCl2, the serum levels were significantly
      higher and urinary excretion of T-3761 was significantly lower than in normal
      rats. Above results show that T-3761 has unique characteristics in absorption,
      excretion and distribution after oral administration to animals among new
      quinolones, i.e., T-3761 was eliminated rapidly and poorly distributed to tissues
      but showed superior absorption and high peak serum levels.

PMID- 7637198
TI  - [Serum protein binding of T-3761].
AB  - We investigated the extent of the binding of T-3761 to serum protein and obtained
      the following results. 1. The binding rates of T-3761 to serum protein from
      various animals and human were 16.9-27.7%, and a little higher than those of
      ciprofloxacin and ofloxacin. 2. The binding rates of T-3761 to human serum
      protein were 19.1-23.8% at concentrations of 0.25-20 micrograms/ml. 3. The
      binding rates of T-3761 lowered as the decrease of protein concentration. 4. The
      binding rates of T-3761 (2 micrograms/ml) to human serum protein were 12.4, 21.3
      and 32.1% at pH 7.0, 7.4 and 8.0, respectively, showing the effect of the pH. 5.
      The binding of T-3761 to human serum protein was reversible. 6. In vivo binding
      rates of T-3761 in rabbits after a single oral administration of 20 mg/kg were
      26.1-33.2%, which were similar to those obtained in vitro.

PMID- 7637200
TI  - [Study of metabolism of T-3761 in animal].
AB  - The metabolism of T-3761 in mouse, rat, rabbit, dog and monkey was studied. Four
      metabolites, other than unchanged T-3761, were detected and identified as
      follows: T-3761 glucuronide; T-3761M1, adduct of glucose; T-3761M2 and T-3761M3,
      compounds metabolized at 1-aminocyclopropyl ring. In urine of mouse, T-3761
      glucuronide was mainly detected, but in urine of other animals, T-3761 was mainly
      detected.

PMID- 7637199
TI  - [Mechanism of renal excretion of T-3761, a novel fluoroquinolone agent, in
      rabbits].
AB  - The mechanism of the renal excretion of T-3761, a novel oral fluoroquinolone
      agent, was studied by renal clearance, stop-flow techniques and analyzing the
      pharmacokinetics with and without probenecid in rabbits, and which were compared
      with those of ofloxacin (OFLX). In rabbits probenecid treatment induced increases
      in the elimination half-life (2.1 times higher) and area under the serum
      concentration-time curve (3.1 times), and decreases in elimination rate constant
      (0.44 times) and total body clearance (0.35 times), while volume of distribution
      showed no significant change. In the stop-flow pattern, a specific peak of T-3761
      was observed. On the other hand, a peak of OFLX was observed at the peak of PAH
      and a small trough at the trough of sodium. And the renal clearance of T-3761 and
      OFLX were about 4.9 and 3.3 times higher than the corresponding Clcr,
      respectively. These results suggested that T-3761 was excreted into urine by both
      glomerular filtration and renal tubular secretion, and was scarcely reabsorbed at
      distal tubule. The short elimination half-life of T-3761 might be explained by
      its great ratio of tubular excretion.

PMID- 7637201
TI  - [Affinity of T-3761 to ocular melanin and intraocular dynamics].
AB  - The affinity of T-3761 to melanin was examined with synthetic melanin comparing
      other quinolones. The binding rates with synthetic melanin were from 37% to 48%
      for tosufloxacin, sparfloxacin, ciprofloxacin and norfloxacin. Binding rate of
      ofloxacin at 28% was lower and T-3761 was lowest at 22%. Intraocular dynamics of
      T-3761 and ofloxacin were investigated in pigmented rabbits after a single oral
      administration at a dose of 20 mg/kg. In both drugs, the concentrations in the
      melanin bearing tissues were higher and the disappearances from the melanin
      bearing tissues were more slowly than those of the non-melanin bearing tissues. T
      3761 concentrations in the melanin bearing tissues were significantly lower than
      ofloxacin. In vitro uptake amount to melanin bearing tissue of ofloxacin was 1.4
      2.4 times larger than that of T-3761.

PMID- 7637202
TI  - [Absorption, distribution, excretion and metabolism of [14C] T-3761 in rats and
      mice].
AB  - Absorption, distribution, excretion and metabolism were studied in rats and mice
      after oral and intravenous administration of 5 mg/kg of [14C] T-3761. 1. [14C] T
      3761 was rapidly absorbed after oral administration and maximum serum
      concentration of radioactivity was observed at 15 min. and at 10 min. in rats and
      mice, respectively. After that, radioactivity of serum declined rapidly. 2. The
      administered radioactivity was excreted mainly in the urine in rats and mice and
      excretion rate was 84% and 74%, respectively. The residual radioactivity was
      excreted in the feces. In both species, the urinary excretion rate after oral
      administration was similar to that after intravenous administration, suggesting
      that [14C] T-3761 was absorbed almost completely. 3. In the rat urine, over 90%
      of excreted radioactivity was T-3761. On the other hand, about 57% of excreted
      radioactivity was presumed to be glucuronide conjugate of T-3761 in the mice
      urine. 4. The biliary excretion of radioactivity in rats after oral
      administration was approximately 22%, and about 83% of those was presumed to be
      glucuronide conjugate. About 40% of the excreted radioactivity was reabsorbed
      from the intestinal tract. 5. Except gastrointestinal tract, tissue concentration
      of radioactivity after oral administration was high in kidney and liver.
      Radioactivity was widely distributed in other tissues at lower concentration than
      in the plasma, whereas hardly distributed in brain and spinal cord. 6. Whole body
      autoradiograms in rats indicate that radioactivity were widely distributed except
      central nervous systems. 7. The extent of the binding of [14C] T-3761 to serum
      protein was 23-31% and 25-34% in rats and mice, respectively.

PMID- 7637203
TI  - [Placental transfer and mammary excretion of [14C] T-3761 in rats and mice].
AB  - Placental transfer and mammary excretion of radioactivity were investigated in
      the pregnant rats on day 19 of pregnancy, in the pregnant mice on day 18 of
      pregnancy, and in the lactating rats after oral administration of 5 mg/kg of
      [14C] T-3761. 1. Transfer of radioactivity to fetus was observed in rats and mice
      and the concentration in fetus was 0.2-0.5 times higher than the maternal plasma.
      2. The radioactivity was excreted into the milk and the concentration in milk was
      higher than those of blood levels (milk/blood = 1.3-5.8). The radioactivity in
      milk declined more slowly than in blood.

PMID- 7637204
TI  - [General pharmacology of T-3761, a new oral quinolone antibacterial agent (1).
      Effect on the central nervous system].
AB  - General pharmacological effects of T-3761, a new oral quinolone antibacterial
      agent, on the central nervous system were investigated in laboratory animals. The
      results obtained are summarized as follows. 1. T-3761 exerted no significant
      effects on spontaneous motor activity, motor coordination, pentobarbital-induced
      hypnosis, electroshock-, pentetrazole- or strychnine-induced convulsion, acetic
      acid-induced writhing responses, reserpine-induced hypothermia and ptosis in mice
      at oral doses of 100, 300 and 1,000 mg/kg. The same oral doses of T-3761 exerted
      no significant effects on body temperature and passive avoidance response in
      rats. 2. T-3761 had no effects on EEG in cats and spinal reflex in rats at
      intravenous doses of 10, 30 and 100 mg/kg. 3. Convulsions were not observed in
      mice after any oral combinations of T-3761 at a dose of 200 or 1,000 mg/kg with
      14 different nonsteroidal anti-inflammatory drugs (NSAIDs) including fenbufen. 4.
      An oral combination of T-3761 even at a higher doses of 3,000 mg/kg with 4
      biphenylacetic acid (BPAA) which is a principally active metabolite of fenbufen
      also did not induce convulsions in mice. 5. T-3761 did not inhibit GABA receptor
      binding in rat brain synaptic membranes at 10(-4) M in either the absence or
      presence of BPAA. These results suggest that T-3761 is an antibacterial agent
      which would be unlikely to produce any side effects on the central nervous system
      and to produce convulsion when combined with NSAIDs in clinical use.

PMID- 7637205
TI  - [General pharmacology of T-3761, a new oral quinolone antibacterial agent (2).
      Effect on the respiratory and cardiovascular systems, autonomic nervous system
      and other functions].
AB  - General pharmacological effects of T-3761, a new oral quinolone antibacterial
      agent, on the respiratory and cardiovascular systems, autonomic nervous system
      and other functions were investigated in laboratory animals. The results obtained
      are summarized as follows. 1. Respiratory and cardiovascular systems: Oral
      administration of T-3761 at doses of 100-1,000 mg/kg did not affect in conscious
      rats. But intravenous administration of T-3761 at doses of 10-100 mg/kg caused an
      increase in respiratory rate, induced hypotension, caused increase or decrease in
      heart rate and altered ECG patterns (elevation of T waves and reduction of
      voltage of QRS complexes, etc.) in anesthetized dogs. Intravenous administration
      of T-3761 at doses of 10-100 mg/kg showed respiratory rate increase or decrease,
      hypertension, heart rate decrease and ECG patterns changes (T waves elevation and
      extrasystole) in anesthetized rabbits. 2. Autonomic nervous system and smooth
      muscle organs: T-3761 increased the epinephrine-induced contraction of the
      isolated guinea pig vas deferens at concentration of 10(-5)-10(-4) g/ml. T-3761
      decreased the acetylcholine-induced contraction of the isolated guinea pig ileum
      and epinephrine-induced relaxation of the isolated guinea pig trachea-chain at
      concentration of 10(-4) g/ml. T-3761 increased the norepinephrine-induced
      contraction of the isolated rabbit thoracic aorta at concentration of 10(-4)
      g/ml. Oral administration of T-3761 at a dose of 1,000 mg/kg exerted slight
      mydriasis in mice. 3. Digestive system: T-3761 decreased the spontaneous
      motilities of isolated ileum and colon at concentration of 10(-4) g/ml. Oral
      administration of T-3761 at a dose of 1,000 mg/kg inhibited gastric output and
      intestinal transit time in rats or mice. 4. Renal functions: Oral administration
      of T-3761 at a dose of 300 mg/kg increased Na+ excretion but did not affect PSP
      excretion in rats. 5. Hematological examinations: T-3761 showed no effects on
      resistance to hemolysis, blood coagulation and platelet aggregation in rabbits at
      concentration of 10(-6)-10(-4) g/ml. Oral administration of T-3761 at dose of 100
      1,000 mg/kg did not affect bleeding time or blood glucose level in rats. 6.
      Miscellaneous effects: Intravenous administration of T-3761 at a dose of 100
      mg/kg slightly inhibited the twitch tension of gastrocnemius in anesthetized
      rats. Oral administration of T-3761 at doses of 300-1,000 mg/kg exerted slight
      augmentation of carrageenin-induced hind paw edema in rats. From these results,
      it can be assumed that T-3761 had a wide safety margin as an oral antibacterial
      agent.

PMID- 7637206
TI  - [A study of urinary podocalyxin in children with IgA nephropathy].
AB  - The existence of podocalyxin (PCX) in urine sediments of 30 children with IgA
      nephropathy was identified by positive findings of immunofluorescence testing
      using a monoclonal antibody (PHM-5). Three structures (cells (podocytes), casts,
      granules) were stained and arbitrarily scored according to their numbers and
      intensity of fluorescence. The urinary scores for podocytes and casts were higher
      in the acute stage than in the chronic stage (p < 0.02 and p < 0.01,
      respectively). Protein excretion and hematuria showed a strong parallel
      correlation in the podocytes (p < 0.005 and p < 0.001), and in the casts (p <
      0.001 and p < 0.005) in the urine sediments. The urinary scores for podocytes and
      casts were significantly higher in cases with extracapillary lesions (p < 0.003
      and p < 0.01) and with interstitial lesions (p < 0.02 and p < 0.008) but no
      correlation existed with the intensity of mesangial proliferation. The urinary
      scores for podocytes and casts were also higher in cases with mesangiocapillary
      IgA deposits (p < 0.04 and p < 0.04) and C 3 deposits (p < 0.03 and p < 0.04).
      These findings suggest that PCX in the urine sediments indicate the degree of the
      glomerular epithelial cell injury and is useful for clinical evaluations.

PMID- 7637208
TI  - [Changes in insulin sensitivity after weight loss in hypertensive patients with
      obesity].
AB  - To assess the role of insulin resistance in the hypotensive effect of weight
      loss, insulin sensitivity was examined by the euglycemic insulin clamp method in
      15 untreated obese hypertensive patients with a body mass index of 25 kg/m2 or
      greater (4 men and 11 women, with a mean age of 53.4 years) before and 4 weeks
      after being placed on a low-calorie diet of 800 Cal/day with mild exercise. Body
      weight decreased by 11.0% (from 74.3 +/- 3.8 to 66.1 +/- 3.0 kg; p < 0.01) with a
      concomitant fall of mean blood pressure from 122.5 +/- 2.3 to 108.6 +/- 2.4 mmHg
      (p < 0.01). Glucose infusion rate (GIR), as an index of insulin sensitivity, was
      significantly increased by 54.3% (from 3.66 +/- 2.4 to 5.5 +/- 9.3 ml/kg/min; p <
      0.01). Plasma levels of fasting blood sugar and insulin decreased significantly
      by 11.8% and 58.4%, respectively (both p < 0.01). The change in mean blood
      pressure showed a negative correlation with the change in GIR resulting from
      weight loss (r = -0.79, p < 0.05). These findings suggest that the hypotensive
      effect of weight loss in hypertensive patients with obesity is partly related to
      improvement of insulin sensitivity.

PMID- 7637207
TI  - [Chylomicron and VLDL metabolism in daunomycin-induced nephrotic rats].
AB  - Lipid metabolism in chylomicron and VLDL were examined in daunomycin-induced
      nephrotic rats. 1) There was no difference in intestinal cholesterogenesis
      between the control rats and daunomycin-induced nephrotic rats. 2) The apoprotein
      content of chylomicron and VLDL increased in daunomycin-induced nephrotic rats.
      3) Daunomycin-induced nephrotic rats showed increases in the content of apo B-48
      and C-III, and a decrease in that of apo E in chylomicron. The apoprotein
      composition of VLDL in daunomycin-induced nephrotic rats showed increased apo B
      and decreased apo E. These results suggest that increased chylomicron-cholesterol
      is not due to increased intestinal cholesterogenesis, but to decreased
      chylomicron catabolism in daunomycin-induced nephrotic rats. Increased apoprotein
      in VLDL may contribute to the decreased catabolism by reducing LPL activity in
      the plasma and increased secretion from the liver of daunomycin induced nephrotic
      rats.

PMID- 7637209
TI  - [Clinicopathological study of IgA nephropathy: the influence of age on renal
      histological changes and prognosis].
AB  - Clinicopathological features and prognosis were studied in 291 Japanese patients
      (4 to 60 years of age) with IgA nephropathy to investigate the influence of age
      on this disease. Histological assessment was done using the semiquantitative
      scoring system consisting of the activity index (A1) and chronicity index (C1).
      1) Cl scores, especially global glomerulosclerosis and tubulointerstitial change,
      markedly increased with age, while Al scores slightly increased. 2) The Cl scores
      and rate of chronic renal failure (CRF) increased, especially in patients beyond
      30 years of age. 3) A higher rate of CRF or regular hemodialysis was found in
      patients with Cl > or = 4 compared to those with Cl < 4 (21.7%, 2.9%
      respectively). These results suggest that chronic, irreversible histologic
      changes increase with age, especially beyond the age of 30 years, which worsens
      the prognosis of patients with IgA nephropathy.

PMID- 7637210
TI  - [Measurement and clinical significance of serum concentrations of pyridinium
      cross-links in patients with renal osteodystrophy].
AB  - Serum concentration of the pyridinium cross-links, pyridinoline (Pyr) and
      deoxypyridinoline (Dpyr), which are markers of bone resorption, was measured by
      high-performance liquid chromatography in 56 patients on maintenance
      hemodialysis. The following analyses were conducted: 1) correlation with known
      markers of bone metabolism, 2) correlation with findings on bone changes on plain
      X-ray film, 3) elimination rates by hemodialysis, and 4) increment per day in
      pyridinoline after hemodialysis (delta Pyr/day). There was a very close
      correlation found between serum Pyr and Dpyr (r = 0.861). Both serum Pyr and Dpyr
      showed correlations with known markers of bone metabolism: C-PTH (r = 0.806 and r
      = 0.747, respectively), M-PTH (r = 0.766 and r = 0.749), osteocalcin (r = 0.717
      and r = 0.693), Alp-3 (r = 0.523 and r = 0.441) and tartrateresistant acid
      phosphatase (r = 0.549 and r = 0.548). In addition, a correlation between the
      duration of hemodialysis and serum Pyr and Dpyr was observed (r = 0.426 and r =
      0.318, respectively). When comparing the mean values of serum Pyr or Dpyr in
      three groups of patients divided according to bone changes seen on plain X-ray
      film, there were statistically significant differences between the group without
      bone changes and the remaining two groups with some bone changes (p < 0.05). A
      mean of 45.3% of serum Pyr was removed by hemodialysis. The serum Pyr level
      returned almost to the original concentration by the following hemodialysis.
      delta Pyr/day showed a close correlation with C-PTH (r = 0.656).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7637211
TI  - [A patients with chronic renal failure due to Bartter's syndrome].
AB  - A male patient with hyperplasia of the juxtaglomerular apparatus, hypokalemia, an
      associated increase in plasma renin activity and hyperaldosteronism without
      hypertension was diagnosed as having Bartter's syndrome at the age of three. He
      was treated with spironolactone, indomethacin and potassium supplements. However
      hypokalemia, increased plasma renin activity and hyperaldosteronism persisted.
      Proteinuria was observed at the age of fifteen. Because of the gradual reduction
      of his renal function, the patient was admitted to our hospital and underwent
      hemodialysis at the age of twenty-one. He was normotensive. Serum potassium was
      within the normal range. Plasma renin activity and aldosterone concentration
      levels were still elevated. Renal biopsies, which had been carried out four times
      throughout his treatment, revealed an increase in sclerosis of the glomerular
      mesangial region, and interstitial fibrosis in proportion to narrowing of the
      small arteries in association with the juxtaglomerular hyperplasia. These
      findings suggested that changes in the glomeruli and interstitium of the kidney
      were secondary to long-standing hypokalemia, stenosis of the small arteries and
      the effects of the prescribed drugs for Bartter's syndrome.

PMID- 7637212
TI  - [A familial case of ADPKD with intracranial aneurysms detected by MR
      angiography].
AB  - The management and screening of unruptured asymptomatic intracranial aneurysm
      (ICA) in patients with ADPKD and those with a family history of ICA remains a
      subject of considerable controversy. In recent years, it has been revealed that
      MRA (magnetic resonance angiography) can define the circle of Willis to allow
      detection of ICA as small as 3-4 mm. We report a case of a 63-year-old man with
      ADPKD and his family. No definite aneurysm was observed by angiography screening
      at 46 years of age, when he was referred for hemodialysis. For the past three
      years, his family history revealed that three relatives were suffering from
      subarachnoid hemorrhage at the ages of 32, 36 and 39 years, respectively, two of
      whom had ICA and one had arterio-venous malformation detected by angiography.
      Whether they had ADPKD was unknown, but two were suggestive of ADPKD. Therefore,
      our case underwent MRA as screening for ICA, which showed an ICA with a diameter
      of 5mm in the anterior communicating artery. The ICA was confirmed as being 6 mm
      in diameter by conventional angiography. His niece and her son, who had ADPKD,
      also underwent MRA, which showed a suspicious image of a 2 mm ICA in the latter
      case. These results suggest that prophylactic screening for ICA is important in
      an ICA clustering family. MRA is useful in screening for ICA and in the follow-up
      study on the natural course of ICA.

PMID- 7637213
TI  - [Aortic arch aneurysm: new modification of aortic arch reconstruction and
      selective cerebral perfusion].
AB  - Selective cerebral perfusion (SCP) has been widely used as the method for
      cerebral protection during aortic arch repair in the treatment of aortic arch
      aneurysms in our institution. Recently, we modified our technique of aortic arch
      reconstruction and SCP in order to reduce the neurological complication.
      Following institution of SCP into both innominate and left common carotid
      arteries at 22 degrees C, the distal graft anastomosis and left subclavian
      reconstruction were performed while the descending aorta was left opened. Then
      the antegrade perfusion with rewarming was started via the fourth limbs attached
      to the main graft instead of the femoral artery. The aortic arch was completely
      replaced with the graft with three limbs for arch vessels. During one-year period
      from December 1993 to November 1994, 30 patients were operated on for aortic arch
      aneurysms using this technique. The etiology of aneurysms was true aneurysms in
      16 patients, and aortic dissection in 14 including 8 cases of acute dissection.
      The concomitant procedures included descending graft replacement in 11 patients,
      composite graft replacement in 5, CABG in 3, and AVR in 1. The hospital mortality
      was 3.3% (1 of the 30 patients). There was no neurological complication. We
      conclude that the present techniques are useful methods for preventing the
      neurological complication in the treatment of aortic arch aneurysms.

PMID- 7637214
TI  - [Hemodynamic response to pericardiectomy in the patients with constrictive
      pericarditis: with reference to surgical approaches and responses to exercise].
AB  - Between 1975 and 1994, we performed 20 pericardiectomies for 19 patients with
      constrictive pericarditis (CP) through a median sternotomy (13 cases), a left
      thoracotomy (2 cases), a median sternotomy combined with a left thoracotomy (4
      cases) or a median sternotomy under ECC (1 case). One patient died from LOS at
      1st POD due to myocardial failure. Pericardiectomy through a median sternotomy
      decreased RA pressure but PAW pressure did not decrease in some patients. On the
      contrary, pericardiectomy through either a left thoracotomy or a median
      sternotomy combined with a left thoracotomy decreased PAW pressure as well as RA
      pressure significantly. Responses to bicycle exercise demonstrated marked
      elevation of RA and PAW pressures even in a mild case of CP, so that the exercise
      testing seems to be useful for early detection of CP and evaluation of the
      operative results.

PMID- 7637216
TI  - [A percutaneously controllable pulmonary artery banding device: clinical
      application].
AB  - An optimal pulmonary artery banding is often difficult with a conventional
      banding technique. It often requires readjustment after closing the chest. So we
      developed a percutaneously controllable pulmonary artery banding device and
      applied it in three patients. This device consists of silicone balloon being
      pasted on a reinforced silastic plate and silicone reservoir. The balloon is
      applied around the pulmonary artery and the reservoir is implanted
      subcutaneously. The control of the banding is accomplished percutaneously through
      the reservoir using a needle with fluid-filled syringe. This device worked
      successfully in two patients for percutaneous readjustment of pulmonary
      constriction and congestive heart failure was decreased. This device may offer
      proper constriction of the pulmonary artery without any surgical procedures after
      banding and may reduce surgical morbidity and mortality of sick children.

PMID- 7637215
TI  - [A case of lung scar cancer with special pathohistological feature and high CA 19
      9 level].
AB  - A 58-year-old woman complained of cough and fever. CX-P and chest CT revealed
      pneumonic shadow and serum CA 19-9 level was high. Since the malignant cells were
      found in the bronchial lavage fluid, the lower lobectomy of the left lung was
      done. Both macroscopically and microscopically, adenocarcinoma only existed in 2
      3 mm width at the peripheral site of the scar lesion. The postoperative CA 19-9
      values continued to be high, suggesting the recurrence of the cancer. After 23
      months from the first operation, the upper lobe of the left lung was resected on
      the base of the similar findings in CX-P and chest CT. The histological finding
      of the specimen was compatible with the scar cancer described above. After the
      second operation, the serum CA 19-9 value decreased to normal. We reported a case
      of the lung scar cancer with special pathohistological feature.

PMID- 7637217
TI  - [Risk factors of wound infection following cardiac surgery and antimicrobial
      prophylaxis].
AB  - To make investigation about risk of wound infection following cardiac surgery, we
      analyzed cases of primary aorto-coronary bypass surgery and/or primary valvular
      surgery. Cases required respirator for longer than 2 days, and those with
      drainage tube for longer than 5 days were excluded from this study, because these
      cases had antimicrobial agent postoperatively as therapeutic use rather than
      prophylactic use. Those received preoperative antimicrobial agent for infectious
      endocarditis and so on were also excluded for the same reason. 523 cases were
      entered this study. These cases received cefazolin (CEZ) postoperatively as
      prophylaxis. Sternal wound and leg/groin wound were separately analyzed. Risk
      factors (age, sex, diabetes mellitus, unstable angina, use of intraaortic
      balloon, internal thoracic artery harvest, re-exploration, previous myocardial
      infarction, NYHA classification, emergent operation, operation time,
      extracorporeal circulation time, blood product use, preoperative blood hemoglobin
      concentration, preoperative serum albumin, preoperative creatinine clearance
      (Ccr), duration of drainage tube insertion, body surface area, daily dose of CEZ,
      duration of prophylaxis) were examined using univariate (Chi square test was used
      for contingency table analysis, unpaired t test was used to compare averages) and
      multiple regression analysis. For sternal wound infection, only Ccr showed
      significant (P = 0.027) correlation. For leg/groin wound infection, 2 factors
      (smaller daily dose of CEZ: P = 0.009, more severe NYHA class: P = 0.03) showed
      significant correlation. To investigate appropriate duration of CEZ prophylaxis,
      cases were divided into 2 groups, those had CEZ within 48 hours postoperatively
      (group S) and those had CEZ for longer than 48 hours (group L).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7637218
TI  - [Video assisted lung resection and mediastinal lymph nodes dissection for lung
      cancer: small incisions for 4th intercostal space].
AB  - We established a thoracotomy method in which visual observation and a
      thoracoscope are used in combination. This method requires only small dermal
      incision--a three-cm-long posterior and two-cm-long anterior incision--in the
      fourth intercostal space around the angulus inferior scapulae. Using this method,
      we performed lobectomy and mediastinal lymph node dissection on 20 lung cancer
      cases (preoperatively diagnosed as stage I, T1N0M0 cases). Because the
      conventional thoracoscopic surgery relies strictly on two-dimensional images
      obtained from a thoracoscope, stereoscopic information on the location of the
      operation could not be obtained. Our new method, however, in corporates both a
      direct view obtained from two small incisions and a view on a video monitor, so
      the surgeon has constant access to a stereoscopic information on the location of
      the operation. We found that this thoracotomy using a thoracoscope was not only
      very useful in terms of respiratory function, the alleviation of pain, and
      aesthetic appearance, but that it also reduced hemorrhaging during surgery,
      decreased the length of time required for the thoracotomy and suturing, and
      enabled mediastinal dissection equal to that of standard thoracotomy.

PMID- 7637219
TI  - [New tactile sensor for thoracoscopic detection of intrapulmonary nodules].
AB  - We have developed a new tactile sensor which can be used for thoracoscopic
      detection of invisible intrapulmonary nodules. We applied this new device for
      consecutive ten cases to excise twelve intrapulmonary nodules thoracoscopically
      from August 1994 to January 1995. In this report, one of ten cases was presented.
      The patient was a forty-three-year-old female and admitted with an indeterminate
      nodule on chest X-ray and computed tomography. When the sensor probe quantifying
      the hardness of objects by the changes in resonance frequency of the sensor
      (delta f) passed above the nodule, a sudden jump was evoked in delta f curve on
      the computer screen. The nodule was resected thoracoscopically and proved
      pathologically to be adenocarcinoma. Thoracoscopic procedure was then converted
      to open thoracotomy and lobectomy with lymph node dissection was performed.

PMID- 7637220
TI  - [Surgical management of infective endocarditis in childhood].
AB  - From 1971 to 1993, four patients, 7 to 13 years of age, underwent intracardiac
      operation for infective endocarditis. Two patients underwent mitral valve
      replacements, one was tricuspid replacement and one received tricuspid
      valvulectomy. There was no operative death but one late death occurred
      (correction of occurred) due to cerebral bleeding. Surgical treatment of
      infective endocarditis in childhood could be performed safely by adequate
      selection of operative methods.

PMID- 7637221
TI  - [Complications of endocardial biopsy in heart transplant patients].
AB  - Despite the increasing use of alternative techniques, endomyocardial biopsy
      remains the primary method for diagnosing cardiac allograft rejection. Between
      March 1986 and May 1994, 2,894 endomyocardial biopsies performed on 183 heart
      transplant patients were reviewed. A total of 53 (1.8%) complications occurred.
      33 (1.1%) complications were associated with the introduction, including carotid
      puncture (0.9%), neurological reaction (0.1%), and pneumothorax (0.1%).
      Complications during biopsy included arrhythmias (0.4%) and ventricular
      perforation (0.2%). In addition, we observed three episodes of allergic reaction
      to a reusable biotome, three episodes of liver biopsy, and one case of pacemaker
      dislodgement. All complications were without significant long-term sequelae. In
      contrast to the cardiomyopathy population, no severe ventricular perforations or
      deaths occurred. Thus although endomyocardial biopsy has some risk, it continues
      to be a safe and effective way of monitoring rejection.

PMID- 7637222
TI  - [Experience of absorbable staple in lobectomy].
AB  - We examined the differences between absorbable staple and un-absorbable staple in
      inflammatory reaction during the early post-operative period in lung cancer
      patients. From october 1993 to august 1994, absorbable staples (GIA 75-.060;
      United States Surgical Co., Ltd.) or un-absorbable staples (Multifire GIS 60
      Titanium (3.8mm); United States Surgical Co., Ltd.) were applied in 10 lung
      cancer patients each. Duration of air leakage, massive pleural effuion (more than
      100 ml/day), and high fever (over 38 degrees C), as well as the changes of
      leukocyte counts in peripheral venous blood and C reactive protein were compared
      between the two groups. The absorbable staple group show a mildly increased
      inflammatory reactions than those of un-absorbable staple group, but those were
      not significant differences. Absorbable staple was shown to be completely
      absorbed until 6 months in animal model. Absorbable staple is thought to be
      superior to un-absorbable staple, instead of mildly increased inflammatory
      reaction during the early post-operative period.

PMID- 7637223
TI  - [A report of successful surgical management of right coronary artery to right
      atrium fistula forming giant aneurysms at the posterior wall of the right
      atrium].
AB  - A 52-year-old woman was diagnosed by echocardiography to have a fistula of the
      right coronary artery (RCA) and the right atrium (RA). Aortography demonstrated a
      remarkably dilated and undulating fistulous tract originating from the region
      corresponding to the orifice of the normal RCA. The fistulous tract detoured to
      the posterior wall of the RA, and forming 2 aneurysms there, opened to the RA. A
      RCA of normal size originating midway of the fistulous tract was also observed.
      The patient was operated on under cardio-pulmonary bypass. Aortocoronary
      saphenous vein graft to the RCA having normal diameter was performed, and the RCA
      was ligated in the proximal side of the anastomosis. The orifice of the fistulous
      tract from the aorta was closed with a patch and the entrances into the RA were
      also closed by pledgetted mattress sutures. The post operative course was
      uneventful and the patient is now doing well without any complaints.

PMID- 7637224
TI  - [Successful surgical repair of tracheo-innominate artery fistula in a case of ALS
      patient with long-term mechanical ventilation].
AB  - A 59-year-old man with ALS developed dyspnea and was performed tracheostomy in
      September 1987. The cuff volume of a tracheostomy tube increased gradually in
      four years of mechanical ventilation. His chest X-ray in December 1992 showed a
      marked enlargement of the cuff. In March 1993, massive hemorrhage suddenly
      occurred through the tracheostomy site. This was controlled by hyperinflation of
      the cuff. He was diagnosed as tracheo-innominate artery fistula. An emergent
      operation was done by median sternotomy and right oblique cervical incision. The
      innominate artery, the subclavian artery and the common carotid artery were
      severed and occluded with sutures. The tracheal fistula was closed with a suture
      of monofilament. The postoperative course was satisfactory, however he died of
      respiratory failure ten months after the surgery.

PMID- 7637225
TI  - [Chronic left ventricular epicardial pacing by the perforated endocardial
      electrode through the cardiac vein].
AB  - We report a rare complication of endocardial pacing electrode implantation. A 64
      year-old man, who was implanted transvenous pacemaker system by the other
      hospital one month ago, visited our outpatient clinic with the complaint of
      diaphragmatic twitching. Left ventricular pacing was highly suspected because of
      right bandle branch block pattern by 12 leads ECG. Pericardial effusion was
      observed by echocardiography, and angiography revealed the pacing electrode
      coursing through the coronary sinus and perforated the cardiac vein towards the
      posterior wall of the left ventricle. A new generator and a pacing electrode were
      implanted on the other side. Pericardial drainage was not performed because
      hemodynamics was stable. The patient discharged hospital on 18th postoperative
      day without any complication.

PMID- 7637226
TI  - [A case report of corrected TGA with ventricular septal defect, tricuspid valve
      regurgitation and atrioventricular block].
AB  - A 61-year-old woman was admitted for heart failure. She was diagnosed as
      corrected TGA with tricuspid regurgitation, perimembronous ventricular septal
      defect and atrioventricular block by echocardiography and cardiac
      catheterization. We chose tricuspid valve replacement with preservation of valve
      leaflet and subvalvular apparatus, direct closure of ventricular septal defect
      and implantation of permanent pacemaker (myocardial lead). Although IABP was
      needed for 24 hours, after that postoperative course was uneventful. It is
      preferable that tricuspid valve replacement with preservation of valve leaflet
      and subvalvular apparatus is applied to similar adult cases from standpoint of
      morphological structure.

PMID- 7637227
TI  - [Use of epicardial leads for transvenous pacing lead insufficiency with venous
      thrombosis: a case report].
AB  - Recent progress in the electrode tip to prevent dislodgement makes difficult to
      extract itself in some patients. And when multiple leads are placed through a
      transvenous route, more frequent occurrence of venous thrombosis is easily
      suspected. We experienced a case of transvenous lead insufficiency with venous
      thrombosis. In this patient, two of unextractable transvenous leads were already
      placed, and venous thrombosis was detected by venography, so we implanted the new
      epicardial leads instead. In case of long-term placement of transvenous leads,
      especially when multiple, the possibility of venous thrombosis is ever thought,
      and the use of the extractable leads or anticoagulant therapy is recommended.

PMID- 7637228
TI  - [A case of octogenarian left atrial myxoma].
AB  - We reported a case of left atrial myxoma in advanced age. The case was eighty
      years old man. He admitted with congestive heart failure. He was diagnosed as
      left atrial myxoma by echocardiography. The open heart surgery was done. The
      myxoma was 79 g in weight and 8.5x5x3 cm in size. Post operative course was
      uneventful. The echocardiography is useful for diagnosis of the left atrial
      myxoma. The left atrial myxoma should be operated when it is diagnosed how the
      patient is advanced age. The septal-superior exposure gives a good operative
      field.

PMID- 7637229
TI  - [A case of bronchial mucoepidermoid carcinoma in a 7-year-old girl].
AB  - Mucoepidermoid carcinoma of the lung presenting in childhood is extremely
      uncommon. A 7-year-old girl was referred to our hospital with complaint of
      persistent cough and abnormal shadow on the chest roentgenogram. Bronchoscopic
      biopsy revealed a bronchial mucoepidermoid carcinoma and a left pneumonectomy was
      performed. The histopathological examination revealed intermediate grade
      malignancy without any metastasis in mediastinal lymph nodes. She is now doing
      well without any evidence of recurrence 2 years after the operation.

PMID- 7637230
TI  - [Yolk sac tumor resected by transverse sternotomy: a case report].
AB  - Transverse sternotomy was performed in a 39-year-old man having bilateral lung
      metastatic lesions of yolk sac tumor. This approach provided an excellent
      operative field. Bilateral partial lobes including parietal pleura and diaphragma
      were readily resected. As described in this paper, transverse sternotomy is one
      of the beneficial method in the thorough surgical treatment for metastatic
      bilateral lung lesion.

PMID- 7637231
TI  - [A successful case report of conservative treatment of MRSA empyema after right
      pneumonectomy].
AB  - We have successfully treated MRSA empyema after right pneumonectomy by the closed
      drainage and irrigation alone. The patient was a 70-year-old male who had
      received right pneumonectomy for p-III a squamous cell carcinoma originating in
      the right upper lobe bronchus. The operation wound was infected on the 6th
      postoperative day and became pleural fistula and finally MRSA empyema was
      developed on the 10th postoperative day. The chest drainage and irrigation of the
      infected pneumonectomy space with physiological saline containing antiseptic
      povidone iodine (Isodine) were performed 3 times a day for 14 days, however, the
      empyema was not cured completely. In addition, nausea and vomiting considered as
      the side effect of Isodine severely appeared. Therefore the antiseptic agent was
      exchanged to vancomycin hydrochloride from povidone iodine. Empyema space became
      sterile 4 days after the exchange and the drainage tube was removed 7 days after
      sterilization. Further empyema has not been developed for 8 months. We discussed
      the method and antiseptic agents in irrigation of empyema space.

PMID- 7637232
TI  - [A case of giant bronchogenic cyst complicated with postoperative esophageal
      perforation].
AB  - A 42-year-old man with giant bronchogenic cyst occupied from the middle and
      posterior mediastinum was treated surgically. The tumor was stoutly adhered to
      anterior aspect of the esophagus and membranous portion of the right bronchus. In
      dissecting the tumor, muscular coat of the esophagus was partly severed, which
      was repaired interruptedly with absorbable suture material. However, esophageal
      perforation was detected by barium swallow on the 3rd postoperative day.
      Conservative therapy included intrathoracic drainage and antibiotics was
      successfully undertaken. It is imperative to dissect the tumor very carefully if
      the giant bronchogenic cyst adheres to the esophagus or other surrounding organs.

PMID- 7637234
TI  - [Contractile proteins and calcium ion in urology].

PMID- 7637233
TI  - [Postoperative bronchial stenosis associated with IAA complex and transendoscopic
      resection of intrabronchial granulation].
AB  - Problem with stenosis of the left bronchus was encountered in a patient with type
      B interrupted aortic arch complex after the arch reconstruction and pulmonary
      artery banding. Bronchoscopic study disclosed the intraluminal granulation of
      left bronchus and transendoscopic resection of the granulation successfully
      relieved the stenosis and brought the patient to full recovery.

PMID- 7637236
TI  - [Molecular genetic analysis of a family with von Hippel-Lindau disease].
AB  - We analyzed germline mutations of the von Hippel-Lindau (VHL) gene located at
      chromosome 3p25 in a family of VHL disease by using single strand conformational
      polymorphism (SSCP) and Southern blot analyses. In 10 individuals including 2
      patients with multiple renal cell carcinomas, multiple pancreatic cysts and
      cerebellar hemangioblastoma, there are no positive results in SSCP analysis.
      However, in 2 patients and one kindred, same abnormal band was observed in
      Southern blot analysis. Moreover, in this one kindred of 17 years old girl,
      multiple pancreatic cysts were found by computerized tomography (CT). These
      results shows the alteration in the VHL gene is a major rearrangement but not a
      small mutation and this alteration caused VHL disease in this family.
      Furthermore, presymptomatic diagnosis by direct mutation analysis seems to be
      very useful for early detection of this disease.

PMID- 7637237
TI  - [Studies of spermatogenic damages induced by anti-cancer agent and anti
      androgenic agents in rat testes].
AB  - To investigate the mechanisms responsible for and recovery process of
      spermatogenic damage induced by anti-cancer agent and anti-androgen agents, we
      experimented with rats injected with those agents. Cis-diamminedichloroplatinum
      (CDDP) was selected as the anti-cancer agent causing spermatogenic damage.
      Flutamide and cyproterone acetate were selected as anti-androgen agents. Both of
      these agents induced histopathological spermatogenic damage. The influences of
      CDDP on spermatogonia and spermatocytes were remarkable, compared with
      cyproterone acetate and flutamide, which damaged mainly spermatids. CDDP had
      severely damaging effects on the DNA-synthesizing activity of spermatogenesis,
      based on findings using monoclonal antibody proliferating cell nuclear antigen
      (PCNA), compared with anti-androgen agents. We also studied Sertoli cell function
      of drug-induced spermatogenic damage in rat testes. Measuring the contents of
      transferrin in rat testes indicated the damage to Sertoli cell function. High
      doses of CDDP (8 mg/kg) affected testicular transferrin concentration, but 4
      mg/kg and 2 mg/kg of CDDP had no significant effect on Sertoli cell function.
      Cyproterone acetate and flutamide had severely damaging effects on Sertoli cell
      function not only at a high dose (30 mg/kg) but at low doses of 15 mg/kg and 7.5
      mg/kg. These results showed that an anti-cancer agent primarily affects the DNA
      synthesizing activity of spermatogonia and spermatocytes, but high doses of these
      agents also have damaging effect on Sertoli cells, and anti-androgen agents
      mainly affect Sertoli cells.

PMID- 7637235
TI  - [The expression of the E-cadherin in human urinary bladder carcinoma].
AB  - We examined immunohistochemically the expression of E-cadherin which is Ca2+
      dependent intercellular adhesion molecules in bladder carcinoma and investigated
      the correlation among the expression of E-cadherin, pathological examination,
      clinical findings and course. Fifty cases of bladder carcinoma were examined
      except one squamous cell carcinoma. The pattern of the immunohistochemical
      staining by E-cadherin antibody were classified into 4 groups as follows. The
      tumor, over 75% of which cells were stained like normal epithelium, was regarded
      as (2+). When from 50% to 75% of the carcinoma cells were stained, it was (+).
      When from 25% to 50% of the carcinoma cells were stained, it was (+/-). The tumor
      showing that under 25% of the cells were stained or lack of staining was regarded
      as (-). It was demonstrated that the percentage of positive staining was
      significantly lower in cases of high grade or high stage tumors compared with
      those of low grade or low stage. As the pattern of invasion, 88% of the cases
      showing INF alpha was observed as (2+) or (+), while all cases with INF gamma
      showed (+/-) or (-). The patients with superficial tumors showing (+/-) or (-)
      tended to have the higher local recurrence rate of the carcinoma compared with
      those showing (2+) or (+) staining. Immunoblotting analysis demonstrated no
      evidence of gross alteration of E-cadherin molecules between normal and carcinoma
      cells of the bladder. In conclusion, the decrease of E-cadherin expression may
      contribute to the tumor grade and invasiveness of bladder carcinoma.

PMID- 7637238
TI  - [Effect of follicle-stimulating hormone (FSH) on protection or acceleration to
      recovery from spermatogenic damage induced by anti-cancer agents].
AB  - We investigated spermatogenic damage induced by anti-cancer agents in previous
      studies. The results showed that the damage to spermatogenesis induced by anti
      cancer agents could be due to not only direct damaging effects on DNA synthesis
      but also a direct effect on Sertoli cell function. Thus, stimulating Sertoli cell
      function could protect against the damaging effects of anti-cancer agents on
      spermatogenesis, or stimulate recovery from impair spermatogenesis. We
      experimented with rats injected with the anti-cancer agents
      cisdiamminedichloroplatinum (CDDP) and adriamycin, which impair spermatogenesis,
      in order to examine this hypothesis. Follicle-stimulating hormone (FSH), which
      should stimulate Sertoli cell function in vivo, was selected, and the effects of
      FSH in protecting against damage or stimulating recovery from damage were
      investigated. The injection of FSH resulted in no significant differences in the
      histopathological findings of spermatogenic damage induced by anti-cancer agents
      or testicular transferrin concentration as compared to those observed without FSH
      injection. But, in the protocol of the experiments on acceleration of recovery
      from spermatogenic damage induced by anti-cancer agents, the spermatid index
      without FSH was 1.02 +/- 0.24, that with FHS 75 IU/kg was 1.50 +/- 0.15, and that
      with FSH 150 IU/kg was 1.62 +/- 0.39, a significant difference (p < 0.05). Also,
      the PCNA labeling index and testicular transferrin concentration were
      significantly different with FSH from those without FSH.

PMID- 7637239
TI  - [Effects of chronic low-frequency electrical stimulation on the external urethral
      sphincter of male rabbits--electrophoretic analyses of myosin light and heavy
      chain isoforms].
AB  - The present study investigates the effects of chronic low-frequency electrical
      stimulation on the external urethral sphincter (EUS) of rabbits through the
      biochemical analysis of the isoforms of myosin light and heavy chains. Twenty
      eight adult male rabbits were used in the test. Of these, the EUS of 14 rabbits
      were continuously stimulated directly at 1.8 Hz, 0.8 msec, 5.0 V with an
      implantable electrical cardiac pacemaker for more than 10 weeks. The other 14
      rabbits were used as the control group and were nurtured under the same
      conditions as the stimulated group but without the electrical stimulation. Upon
      conclusion of the stimulation program, the urethra was removed from all 28
      rabbits. The portion of the urethra containing the EUS (from the middle of the
      prostate to the pelvic diaphragm) was cut transversely into thin serial sections
      and glycerinated. The glycerinated muscle fibers were then isolated under a
      stereomicroscope and samples for electrophoretic analysis were prepared. Two
      dimensional electrophoresis according to the procedure of O'Farrell for myosin
      light chains and SDS-PAGE containing 40% glycerol for myosin heavy chains were
      carried out. The molar ratio of myosin subunits was determined by quantification
      through the dye elution process. The average percentages of slow myosin light
      chain molecules in 8 unstimulated and 8 stimulated EUS were 33.4 +/- 8.9% (mean
      +/- SD) and 70.1 +/- 12.8%, respectively. The average percentages of slow myosin
      heavy chain molecules in 6 unstimulated and 6 stimulated EUS were 17.6 +/- 5.7%
      and 40.2 +/- 7.1%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7637240
TI  - [Treatment of stone street after extracorporeal shock wave lithotripsy of
      staghorn calculi].
AB  - During ESWL monotherapy for staghorn calculi, the formation of a stone street in
      the ureter is often encountered, and can be a troublesome problem. At the Komaki
      Shimin Hospital, 75 patients with staghorn calculi were treated with ESWL
      monotherapy using a Dornier HM-3 lithotriptor between October 1987 and August
      1992. Among them, three patients had involvement of both collecting systems. An
      indwelling double J catheter was always inserted during treatment. Our strategy
      for the treatment of stone street was as follows; observation was initially
      performed for one month after ESWL, as long as pyelonephritis and/or complete
      obstruction did not occur. In the patients without any improvement of the stone
      street, TUL or ESWL was then performed for removal. A stone street (stone
      fragments extending > or = 4 cm) was formed in 38 of 78 renal units (49%). In 14
      cases (37%), it disappeared spontaneously. TUL was required in 14 unit (37%),
      ESWL in eight units (21%), and both procedures in two units (5%). In one unit
      (3%), renal function was severely damaged. In another unit, ureteric perforation
      occurred during the TUL procedure, and caused stone loss outside the ureter. To
      clarify the factors causing stone street, we compared the number of shock waves,
      the size of the stones, the severity of hydronephrosis and renal function in
      stone street formers and non-formers. However there were no significant
      differences among these factors. In conclusion, since it is impossible to predict
      stone street formation after ESWL monotherapy for staghorn calculi, patency of
      the indwelling double J catheter should be maintained and stone removal should be
      attempted after one month if necessary.

PMID- 7637241
TI  - [Nephron sparing surgery of patients with renal cell carcinoma in a solitary
      kidney or bilateral renal cell carcinoma].
AB  - PURPOSE: The objective of this study is to evaluate the efficacy of nephron
      sparing surgery for renal cell carcinoma in patients with a solitary kidney or
      bilateral tumors. PATIENTS AND METHODS: From 1982 to 1994, a total of 12 patients
      with a solitary kidney or bilateral tumors underwent nephron sparing surgery. The
      survival and complications were examined. RESULTS: The patients were 11 males and
      1 female. Three patients were in stage 1, 6 in stage 2, 2 in stage 3, and 1 in
      stage 4, and the mean tumor size was 3.4 cm (0.8-6.5). The complications were
      post-operative bleeding in one patient and slight transient renal dysfunction
      which didn't require hemodialysis in 3 patients. The local recurrence was
      observed in 1 patient (8.3%), metastasis in 3 (25%), no evidence of disease in 8
      (66.7%), alive with cancer in 1 (8.3%), death due to cancer in 2 (16.7%), death
      due to other disease in 1 (8.3%), and the 5 year survival of all patients was
      62.5%, that was almost the same as the result of 141 renal cell carcinoma
      patients treated with nephrectomy in our hospital. The disease free survival rate
      of the patients in stage 1 and 2 seems to be higher than in stage 3 and 4 with no
      significant difference (p = 0.0956). CONCLUSION: These results suggest that
      nephron sparing surgery for renal cell carcinoma in patients with a solitary
      kidney or bilateral tumors is a useful therapy.

PMID- 7637242
TI  - [Magnetic resonance imaging for the evaluation of prostate cancer metastatic to
      bone].
AB  - The response of bone metastatic lesions to endocrine therapy was assessed by
      repeated magnetic resonance imaging (MRI) and an isotope bone scan after an
      average period of 7.0 months (2-10 months) in 12 patients with prostate cancer.
      MRI used both T1-weighted spin echo technique and short TI IR (STIR) sequence. Of
      7 patients with hormone-dependent cancer, the bone metastatic lesions resolved or
      became vague in all patients on STIR image, while in only 4 and 3 on T1-weighted
      image and bone scan, respectively. Of 5 patients with hormone-refractory cancer,
      the lesions progressed on both MRI and bone scan in all patients except one who
      had initially had diffusely metastatic lesions of systemic bone. The results
      indicate that STIR image of MRI is helpful for the therapeutic evaluation of bone
      lesions.

PMID- 7637243
TI  - [Neoadjuvant endocrine therapy prior to nerve-sparing radical prostatectomy in
      patients with stage T2 prostatic cancer].
AB  - Radical prostatectomy is the effective treatment for clinical T2 prostatic
      cancer. However, clinical T2 stage is often understaged preoperatively. The
      objective of neoadjuvant therapy is to increase the curability of surgery to
      understaged patients. The present study was based on patients who had had
      neoadjuvant endocrine therapy (LH-RH agonist) prior to radical nerve-sparing
      prostatectomy for T2 prostatic cancer. Sexual function were estimated before and
      after surgery. Ten patients with a mean age of 64.6 years (range 57-71 years) and
      biopsy-proven cancer received this treatment modality. No patients had evidence
      of lymph node metastasis by the pelvic computerized tomography and their bone
      scan was negative for metastasis. Clinical stage was T2a in 3 patients and T2b in
      7. The grade of these tumors as assessed on prostatic biopsy before neoadjuvant
      endocrine treatment was well differentiated in 3 and moderately differentiated in
      7. The duration of neoadjuvant endocrine therapy was 3.6 months (range 2-5
      months) in average. Serum levels of prostatic specific antigen (PSA) were
      examined monthly and prostate volume was measured by transrectal ultrasonography
      before and after neoadjuvant treatment. Decrease in serum PSA values was observed
      from an average level of 8.6 ng/ml (range 3.1-17.5 ng/ml) determined prior to
      neoadjuvant treatment to an average of 1.1 ng/ml (range 0.6-3.3 ng/ml) determined
      after neoadjuvant treatment. An average reduction of prostatic volume was 25.3%
      (range 7.4-56.7%) after neoadjuvant therapy. Pathological effects of the
      neoadjuvant therapy by the criteria proposed by Japanese Urological Association
      were Grade (G) 0a in 3 patients, G0b in 4, G1 in 2 and G2 in 1. Of patients who
      had 10 stage T2 cancer before treatment, 4 had pT2 and 6 pT3.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7637244
TI  - [An analysis of factors related to recurrence of superficial bladder cancer after
      transurethral resection].
AB  - A total of 205 patients with primary superficial bladder cancer (Ta, T1) followed
      more than 3 years were retrospectively analyzed for factors related to recurrence
      of tumors after transurethral resection. Patients age were 25 to 90 years old,
      average 61 years old, and there were 160 males and 45 females. Initial tumor
      grades were G0 in 4 patients, G1 in 48, G2 in 134 and G3 in 19. Seventy four
      patients had Ta tumor and 131 had T1. Initial treatments were transurethral
      resection (TUR) alone in 137 patients. TUR with intravesical chemotherapy in 64,
      with BCG therapy in 7 and others in 7. Factors examined included age, sex, chief
      complaint, shape, size, and number of tumors, tumor distribution (single area or
      multiple area), histological grade, stage and intravesical chemotherapy. Overall
      non-recurrent rate were 81.7% at 1 year, 60.7% at 3 year, 53. 8% at 5 year and
      44.2% at 8 year. Five-year non-recurrent rate according tumor factors, showed
      significant difference regarding tumor size (< 1 cm or 1 cm <: P = 0.027), tumor
      number (single or multiple: P = 0.004), tumor distribution (single area or
      multiple area: p = 0.002), histological grade (< G1 or G2 < : p = 0.001) and
      stage (Ta or T1: p = 0001). However, there were no significant difference
      regarding factors of age, sex, chief complaint, tumor figure and presence or
      absence of intravesical chemotherapy. This results suggested that the tumor
      factors of size, number, tumor distribution, grade and stage were highly related
      to intravesical tumor recurrence of superficial bladder cancer.

PMID- 7637245
TI  - [Prognostic factors for metastatic renal cell cancer].
AB  - We examined various prognostic factors of metastatic renal cell carcinoma.
      Patients who had metastasis at nephrectomy (A group, 38 cases) and those who had
      metastasis as recurrent tumors after nephrectomy (B group, 38 cases) entered in
      this study. Five-year survival rate of total cases after confirmation of
      metastatic foci was 15% and there was no statistical significant difference
      between A and B groups. Several pathological factors were related to poorer
      prognosis and included large diameters of original tumors, positive lymph nodes,
      higher grade tumors and non-clear cell type tumors. Patients who have a solitary
      lung metastasis showed better prognosis compared to those with multiple lung
      metastases or metastases of other organs. Two factors related to treatment were
      shown to contribute to better prognosis. These were the response to interferon
      alfa (IFN alpha) and the possibility of total resection of visible metastatic
      tumors. Patients who belong to A group were shown to achieve markedly better
      therapeutic benefit from IFN alpha or IFN alpha plus anticancer drugs. Five-year
      survival rate for the responders was 40%, as compared to less than 5% for the non
      responders. Ten-year survival rate for patients with metastasis who had undergone
      complete resection of visible tumor was 50%, and the for patients belonging to B
      group Showed 80%. We concluded that these prognostic factors should be considered
      to decide how to select patients with metastatic renal cell cancer.

PMID- 7637246
TI  - [Clinical study of renal cell carcinoma with brain metastasis].
AB  - Of 130 cases with renal cell carcinoma treated at Cancer Institute Hospital from
      January, 1981 to December, 1992, 14 (10.6%) developed brain metastasis, 12 of
      whom had had preceding pulmonary metastasis. Interval between the initial
      treatment of the primary lesion (nephrectomy in 13, embolization in 1) and the
      diagnosis of brain metastasis ranged 0 to 57 months with a median of 11 months.
      Twelve patients had clinical symptoms such as headache, vomiting, paralysis or
      disturbance of consciousness. Eleven patients were treated with external beam
      irradiation (30-60 Gy linear accelerator). Only 3 (30%) of 10 patients with
      measurable lesion on CT scan achieved PR but 6 (66.7%) of 9 had symptomatic
      improvement. Especially, chronic intracranial hypertension such as headache and
      vomiting disappeared in 5 (83.3%) of 6. Average survival period and one year
      survival after the diagnosis of brain metastasis were 5 months and 14.3%.
      Although most of the patients with brain metastasis died of the progression of
      other organ metastasis, radiation therapy for brain metastasis was useful to
      palliate the agonizing symptoms.

PMID- 7637247
TI  - [A case of male infertility with a chromosomal abnormality of 45, X/46, X + mar].
AB  - A 28-year-old man visited our hospital with a complaint of male infertility. His
      development was normal with body size of 169.5 cm in height and muscular type.
      His beard and axillary and pubic hairs were male type. The penis and scrotum were
      also normal, but testes were small (8 ml, bilateral). Semen analysis revealed
      azoospermia. Serum luteinizing hormone (LH) and testosterone levels are within
      normal range but follicle stimulating hormone (FSH) was moderately elevated.
      Testicular biopsy specimen showed severely hyalinized seminiferous tubuli,
      incarceration of basement membrane and hyperplasia of Leydig cells. Johnsen's
      score count was two. Chromosomal analysis revealed a mosaic type of 45, X/46, X +
      mar. We tried to confirm the existence of sex-determining region of the Y
      chromosome (SRY) by the DNA analysis. It was shown that SRY on genomic DNA
      fragment. This marker chromosome may be translocated to a fragment of the short
      arm of Y chromosome.

PMID- 7637248
TI  - [Clear cell sarcoma extending into the inferior vena cava].
AB  - A 6-year-old boy who had been diagnosed as having Wilms tumor at the prior
      hospital was admitted to our hospital for investigation of a right flank mass and
      macrohematuria in October 1990. Magnetic resonance imaging showed Wilms tumor of
      the right kidney extending into the inferior vena cava. Right radical
      nephrectomy, lymphadenectomy and thrombectomy were done on October 30th, 1990.
      Pathological findings indicated clear cell sarcoma of the kidney. One week after
      the operation, radiotherapy and chemotherapy with actinomycin D (ACTD),
      vincristine sulfate (VCR), doxorubicin hydrochloride (DXR) and cyclophosphamide
      (CPM)) were started according to the protocol by National Wilms Tumor Study
      (NWTS) III. However, he died of bone metastases and pneumomycosis on October
      13th, 1992. Clear cell sarcoma of the kidney (CCSK) is a rare tumor accounting
      for about 4-5% of Wilms tumors. This is the first report on CCSK with tumor
      thrombus in Japan.

PMID- 7637249
TI  - [Study on clinical courses of 7 patients undergone resection of adjacent organs
      in the treatment of locally extensive renal cell carcinoma].
AB  - Significance of surgical extirpation of a massive tumor involving adjacent
      viscera is still controversial, because this sort of extensive resection is
      unusual and its results are poor in terms of a short survival time. Here, we
      summarize the clinical courses of 7 patients who had been diagnosed as invasive
      renal cell carcinoma (RCC) and undergone extensive resection of the bowel and/or
      other adjacent visceras. In addition, a percentage of patients who had direct
      invasion and/or metastasis to adjacent viscera in routine autopsies was looked up
      in the Annual Report of the Pathological Autopsy Cases in Japan. Pathological
      diagnosis indicated that direct invasion was confirmed in 4 out of 7 patients.
      One patient was relieved from septic shock due to pelvicocolic fistula caused by
      a direct invasion of RCC. New metastases developed in all patients after the
      radical operation (2 - 30 mos), and 3 of them further underwent resection of the
      metastastic lesion(s). Although 5 patients ultimately died of cancer or its
      related diseases (mean survival time: 14.2 +/- 10.7 mos), other 2 (pT4 and pT3)
      who underwent resection of lung metastasis have survived for 19 and 72 months.
      Either an early occurrence of metastasis after local resection or a tumor
      predominantly composing of spindle cells might indicate a poor prognosis.
      Surgical extirpation should not be precluded when the patient is having severe
      symptoms related to extensive involvement of the adjacent visceras. We believe
      that it is appropriate to individualize in case of choosing patients for such
      extended radical surgery.

PMID- 7637250
TI  - Health care reform: a missed opportunity.

PMID- 7637251
TI  - Certified nurse-midwifery in Kansas: survey of physicians.
AB  - Following U.S. trends, the number of practicing certified nurse-midwives in
      Kansas is growing. Since collaboration with physicians is vital to the successful
      practice of nurse-midwifery, Kansas obstetrician-gynecologists and family
      practice physicians were surveyed regarding certified nurse-midwifery. Seventy
      two randomly-selected physicians received an 11-item questionnaire. The majority
      of responding physicians (n = 40) expressed an interest in certified nurse
      midwifery. Most obstetricians indicated they would consider bringing a certified
      nurse midwife into their practices. Obstetricians were more knowledgeable about
      certified nurse midwifery and were more open to collaboration with nurse-midwives
      than were family practice physicians. Results indicate that the environment is
      ripe for certified nurse-midwife/physician collaboration in Kansas.

PMID- 7637252
TI  - Chronic viral hepatitis and the management of chronic renal failure.
AB  - Effective control measures to reduce the spread of HBV in dialysis units have had
      a major beneficial impact on the management of patients with chronic renal
      failure (Table 3). The exact impact of chronic HBV infection on graft and patient
      survival following RT remains unclear, and the outcome may depend in great part
      on the severity of the pre-RT liver disease. RT should only be offered to HBV
      infected patients after careful consideration of all the pertinent data,
      including results of liver biopsy. Advances in HBV vaccination may further
      decrease the risk of infection in patients on HD. Our understanding of HCV is
      evolving rapidly, but the question of the risk of transmission of HCV within
      dialysis units is still unsettled and thus recommendations about isolation of HCV
      infected patients are not possible. Although RT does not appear to be deleterious
      in many HCV-infected patients, histologic and clinical evidence of severe liver
      disease should also prompt caution in offering RT. Longer term studies are
      required to assess the ultimate effect of RT in patients with HCV. Clearly,
      subjective improvement of quality of life associated with successful RT compared
      to chronic dialysis should not be withheld lightly. Pending further experience,
      use of organs from anti-HCV-positive donors in non-emergent situations is best
      avoided. The role of antiviral agents in RT recipients with chronic viral
      hepatitis also remains to be defined. Improved supportive care of patients with
      chronic renal disease, including erythropoietin therapy, as well as improved
      tests for anti-HCV screening of donor blood will help to further diminish
      exposure to HCV in HD units.

PMID- 7637253
TI  - Charge selectivity in kidney ultrafiltration.

PMID- 7637254
TI  - Reabsorption of nitro-L-arginine infused into the late proximal tubule
      participates in modulation of TGF responsiveness.
AB  - Previous studies indicate that endothelium-derived nitric oxide (NO) can directly
      modulate afferent arteriolar tone and that macula densa-derived NO can indirectly
      regulate afferent arteriolar tone by modulating the tubuloglomerular feedback
      (TGF) mechanism. The present in vivo micropuncture study evaluated whether the
      effect of late proximal tubular perfusion with the nitric oxide synthase (NOS)
      inhibitor, NG-L-arginine (NLA), on TGF responsiveness is related to reabsorption
      of NLA. Late proximal perfusion of 10(-3) M NLA resulted in a gradual, time
      dependent enhancement of maximum TGF-mediated decreases in stop-flow pressure
      (SFP) from -7.1 +/- 0.7 to -19.4 +/- 1.6 mm Hg (P < 0.01). A detailed recording
      of SFP revealed that the maximum response during late proximal perfusion of NLA
      was obtained eight to nine minutes following the initiation of the perfusion,
      whereas maximum TGF responses evoked by late proximal perfusion with ATF were
      reached within one to two minutes. NLA infused into the late proximal segment of
      a neighboring nephron also resulted in enhancement of maximum SFP feedback
      responses from -5.5 +/- 0.5 to -10.4 +/- 1.9 mm Hg (P < 0.05), indicating that
      NLA can be reabsorbed and can consequently influence TGF responses. Finally,
      maximum SFP feedback responses were obtained prior to and following late proximal
      perfusion of 10(-3) M NLA dissolved in ATF, 10(-3) M NLA dissolved in 285 mM
      mannitol, and following perfusion with mannitol without NLA.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7637255
TI  - Glomerular uptake of nucleosomes: evidence for receptor-mediated mesangial cell
      binding.
AB  - DNA-containing immune complexes (IC) are believed to have a central causal role
      in the glomerulonephritis of systemic lupus erythematosus. Extracellular DNA
      which provides the antigenic source for these ICs circulates as oligonucleosomes
      (ON). The in vivo glomerular uptake of radiolabeled ON in rats, as well as its
      binding by cultured rat mesangial cells, was examined. The data show that the
      binding of ON to kidney, and specifically glomeruli, was almost fourfold greater
      than that of purified DNA. Uptake appeared dose-dependent and saturable, while
      there were no differences in hepatic or splenic uptake. Most of the nucleosomal
      DNA recovered from glomeruli was TCA-precipitable, and on gel electrophoresis was
      about 100 to 300 bp, a size sufficient to allow formation of large ICs. In vitro
      studies demonstrated that ON are bound by cultured mesangial cells in a dose
      dependent and saturable manner, with a dissociation constant of 1.25 x 10(-10)
      M/liter and 750 binding sites per cell. Autoradiography of cell cultures
      incubated with radiolabeled ON showed deposition along the plasma membrane which
      was inhibited by excess unlabeled ON. The data show that binding of ON to
      glomeruli exceeds that of purified DNA and may be mediated by histones. ON bind
      to mesangial cells in a receptor-mediated fashion. The data support the
      hypothesis of in situ formation of DNA-containing ICs and suggest a role for the
      mesangial cell in lupus glomerulonephritis.

PMID- 7637256
TI  - Opposite regulation of renin gene expression by cyclic AMP and calcium in
      isolated mouse juxtaglomerular cells.
AB  - A quantitative reverse transcriptase-polymerase chain reaction for mouse renin
      mRNA was utilized to study the influence of classic second messenger molecules on
      renin mRNA levels in primary cultures of juxtaglomerular (JG) cells isolated from
      the kidneys of C57/B16 mice. We found that forskolin (3 microM), an activator of
      adenylate cyclase led to proportional increases of renin secretion and renin mRNA
      levels. The nitric oxide (NO) donor, sodium nitroprusside (100 microM),
      stimulated both renin secretion and renin gene expression, the effect on
      secretion being stronger than that on renin mRNA levels. An increase of the
      extracellular concentration of calcium from 0.5 to 3 mM led to a transient
      inhibition of renin secretion, followed by a marked stimulation of secretion and
      to a continuous suppression of renin mRNA levels. These were also decreased by
      the calcium ionophore A 23187 (1 microM). The membrane permeable 8-bromo-cyclic
      GMP (100 microM) inhibited basal renin secretion without an effect on renin mRNA
      levels. The phorbol ester phorbol-12-myristate-13-acetate (1 to 100 nM), which
      was used to stimulate protein kinase C activity, had no significant effects on
      renin secretion and renin mRNA levels, neither alone nor in combination with
      forskolin. These findings suggest that cAMP, NO and calcium are effective
      regulators of renin gene expression in renal JG cells, in a way that cAMP and NO
      are stimulators and calcium acts as an inhibitor. Moreover, in these acute
      experiments there appears to be no obligatory link between the secretion and the
      expression of renin, suggesting that both parameters are separately regulated.

PMID- 7637257
TI  - Endocytosis and transcytosis of albumin gold through mice peritoneal mesothelium.
AB  - The present transmission electron microscopy (TEM) study was designed to
      investigate whether mesothelial cells of mice diaphragmatic, parietal and
      mesenteric peritoneum are actively coupled to the mechanisms involved in the
      transerosal absorption of albumin gold complexes (Alb-Au). Five albino mice were
      injected intraperitoneally with 0.5 ml of a suspension of Alb-Au. In three
      animals, in vivo fixation was done 10 minutes after injection of Alb-Au, whereas
      in the remaining two, fixation was performed 45 minutes after injection of the
      tracer. At both time intervals, a substantial part of Alb-Au complexes was
      observed within plasmalemmal and coated vesicles, mainly attached to the luminal
      aspect of the internal luminal membranes. The amount of Alb-Au contained in
      plasmalemmal vesicles was significantly higher than that detected in
      intermesothelial junctions. Plasmalemmal vesicles were observed discharging Alb
      Au complexes in the submesothelial interstitium, showing a significantly higher
      proportion of the tracer associated with non-junctional areas. Evidence presented
      in this study supports the idea of local degradation of Alb-Au in mesothelial
      cells after endocytosis, and that of a continuously transcytotic mechanism
      transporting polymerized albumin across the mesothelial layer. In this sense,
      transcytotic vesicles could represent the large pore equivalent.

PMID- 7637258
TI  - Angiotensin II receptor antagonist ameliorates renal tubulointerstitial fibrosis
      caused by unilateral ureteral obstruction.
AB  - Unilateral ureteral obstruction (UUO) results in tubulointerstitial fibrosis of
      the obstructed kidney (OBK). In this study we report that a specific angiotensin
      II (Ang II) receptor antagonists, SC-51316, ameliorates the expansion of the
      renal cortical interstitium in the OBK of the rat at five days of UUO. This is
      similar to the effect of an angiotensin converting enzyme (ACE) inhibitor,
      enalapril. SC-51316 (20 mg/liter in the drinking water) or enalapril (200
      mg/liter in the drinking water) was administered beginning 24 hours before UUO
      and continued through five days after UUO. The relative volume of the
      tubulointerstitium (Vv) was measured by a point-counting method, and
      monocyte/macrophage infiltration, alpha smooth muscle actin (alpha SMA),
      proliferating cell nuclear antigen (PCNA), and collagen type IV (collagen IV)
      protein deposition were examined histologically using specific antibodies. We
      also examined the mRNA levels of transforming growth factor beta 1 (TGF-beta 1)
      and collagen IV by reverse transcription polymerase chain reaction. In untreated
      rats with UUO, Vv was remarkably expanded; collagen IV and alpha SMA protein
      deposition in the interstitium and PCNA labeling of nuclei were increased. These
      changes were significantly ameliorated by administration of an ACE inhibitor or
      an Ang II receptor antagonist. A monocyte/macrophage infiltration was evident in
      the OBK of untreated or Ang II receptor antagonist treated rats but was greatly
      reduced in the OBK of rats given enalapril. Increased expression of TGF-beta 1
      mRNA and collagen IV mRNA was blunted (40 to 75%) by the administration of Ang II
      receptor antagonist or enalapril. The Ang II receptor antagonist or the ACE
      inhibitor did not affect the contralateral kidney of rats with UUO or the control
      kidney of normal rats. This study indicates that the renin-angiotensin system has
      a major role in the pathogenesis of the tubulointerstitial fibrosis of
      obstructive nephropathy. The tubulointerstitial fibrosis of obstructive
      nephropathy is most likely mediated by an increased level of Ang II in renal
      tissue.

PMID- 7637259
TI  - Interleukin-1 receptor antagonist halts the progression of established crescentic
      glomerulonephritis in the rat.
AB  - The pathogenic role of interleukin-1 (IL-1) in the progression of established rat
      crescentic glomerulonephritis was investigated by administration of the
      interleukin-1 receptor antagonist (IL-1ra). Passive accelerated antiglomerular
      basement membrane (GBM) disease was induced in three groups of six rats. One
      group was killed on day 7 with no treatment. The other groups received a constant
      infusion of IL-1ra or saline from day 7 until being killed on day 21. All animals
      developed moderate glomerular injury, a significant loss of renal function and
      marked histological damage including crescent formation by day 7. Saline treated
      animals showed a significant deterioration in these parameters over days 7 to 21.
      In contrast, animals treated with the IL-1ra over this period showed
      stabilization of glomerular injury (protein-uria; P < 0.001) and a recovery of
      normal renal function (creatinine clearance; P < 0.05). Histologically, IL-1ra
      treatment suppressed glomerular cell proliferation (PCNA expression; P < 0.001)
      and significantly inhibited crescent formation (P < 0.005), glomerular sclerosis
      (P < 0.005), tubular atrophy (P < 0.05) and interstitial fibrosis (P < 0.05). A
      key finding was that IL-1ra treatment not only stopped renal leukocyte
      accumulation over days 7 to 21 (P < 0.01), but that treatment also suppressed
      immune activation of the infiltrate (P < 0.01). In conclusion, this study
      provides direct evidence that IL-1 plays a key role in the progressive/chronic
      phase of renal injury in experimental crescentic glomerulonephritis and indicates
      that IL-1ra treatment may be of therapeutic benefit in human rapidly progressive
      crescentic glomerulonephritis.

PMID- 7637260
TI  - Role of adenosine on glucagon-induced cAMP in a human cortical collecting duct
      cell line.
AB  - The hormonal responsiveness profile of the cortical collecting duct varies from
      one species to another. To identify the hormones and agonists that modulate the
      functions of this tubule segment in the human species, we generated a cell line
      (HCD) immortalized by SV40 virus. The tubular origin of this cell line was
      assessed by the expression of collecting duct-specific antigens and the ability
      of vasopressin to increase by nine-fold cAMP synthesis. Glucagon and adenosine
      stimulated cAMP synthesis, and atrial natriuretic peptide stimulated cGMP
      synthesis in a concentration-dependent manner. Bradykinin, adenosine and
      angiotensin increased intracellular calcium concentration ([Ca2+]i). Because
      adenosine can regulate tubular functions, we examined its role on glucagon
      induced cAMP synthesis. Using adenosine analogs, we demonstrated that HCT cells
      both expressed adenosine type-2 (A2) receptors which stimulated cAMP production,
      and adenosine type-1 (A1) receptors linked to [Ca2+]i increase which inhibited
      glucagon-stimulated cAMP synthesis. The inhibitory effect was abolished by
      pertussis toxin, and was neither due to [Ca2+]i increase nor to protein kinase C
      activation, which indicated that some A1 adenosine receptors were directly
      negatively coupled to adenylyl cyclase. These results suggest that adenosine can
      modify human cortical collecting duct functions in opposite ways according to the
      adenosine receptor activated.

PMID- 7637262
TI  - Renal accumulation of streptavidin: potential use for targeted therapy to the
      kidney.
AB  - Streptavidin exhibits a remarkable accumulation in the kidney. Biodistribution
      studies with radio-iodinated streptavidin showed that 70 to 80% of the injected
      dose per gram tissue (%/g) were retained in kidneys of Balb/C mice for three to
      four days compared to less than 5%/g levels in other tissues. This observation
      means that 15 to 20% of the injected dose is accumulated in the kidney, an organ
      that constitutes less than 1% of total body weight. Similar results of percent
      radioactivity per total kidney were obtained in other mouse strains as well as in
      rats and rabbits. Avidin, or the post-secretory form of streptavidin which is of
      a higher molecular weight, do not show any preferential affinity to the kidney.
      The kidney-accumulated streptavidin was mostly confined to the cortex,
      concentrated in the proximal tubular cells. Accumulation of streptavidin in the
      kidney was independent of biotin, since addition of biotin to radio-iodinated
      streptavidin prior to injection did not affect its kidney uptake. Therefore,
      streptavidin, which aquires its kidney accumulation property following truncation
      of the native form, may be utilized for renal specific delivery of
      chemotherapeutic agents, radioactive isotopes and other effector molecules. Such
      ligands can be linked to streptavidin via conventional coupling methods or
      following their biotinylation. Preliminary experiments showed that streptavidin
      can target to the kidney biotinylated ligands or high doses of chemically linked
      radionuclides.

PMID- 7637261
TI  - ACE inhibition prevents renal failure and death in uninephrectomized MWF/Ztm
      rats.
AB  - Many studies have consistently documented that angiotensin converting enzyme
      (ACE) inhibitors prevent proteinuria and glomerulosclerosis in progressive renal
      disease, but very few data are available on whether they also prevent renal
      failure and death. The mechanisms of the beneficial effect of ACE inhibition are
      only partially understood. Recent data suggest that angiotensin II modulates
      renal synthesis of endothelin-1, a vasoactive peptide implicated in the process
      of renal injury. Here we investigated in a long-term study whether ACE inhibition
      ameliorated renal function in uninephrectomized (UNx) male MWF/Ztm rats. Three
      groups of rats at nine weeks of age underwent UNx or sham-operation.
      Nephrectomized animals were left untreated or treated with the ACE inhibitor
      lisinopril in drinking water. In untreated UNx animals systolic blood pressure,
      serum creatinine, urinary protein and renal synthesis of endothelin-1, evaluated
      by its urinary excretion, were significantly increased, as compared with control
      animals with two kidneys. End-stage renal failure developed in all untreated UNx
      rats that died within 9 to 14 months from UNx. ACE inhibitor significantly
      reduced systolic blood pressure, completely prevented proteinuria and renal
      function deterioration, and reduced endothelin-1 excretion. All UNx rats treated
      with lisinopril were alive 14 months after UNx. These results show that ACE
      inhibition prevents end-stage renal failure induced by UNx in male MWF/Ztm, and
      that the beneficial effects of angiotensin II inhibition in this model are
      related to modulation of renal synthesis of endothelin-1.

PMID- 7637263
TI  - Heme protein-induced tubular cytoresistance: expression at the plasma membrane
      level.
AB  - Following experimental rhabdomyolysis, animals become resistant to heme protein
      induced acute renal failure (ARF). The goals of this study were to: (a) ascertain
      whether this resistance, previously documented only in vivo, is expressed
      directly at the proximal tubular cell level; (b) determine whether heme
      proteinuria (vs. other consequences of rhabdomyolysis) is its trigger; and (c)
      ascertain some of its subcellular determinants. Rats were injected with a
      borderline toxic dose of glycerol and 24 hours later proximal tubular segments
      (PTS) were isolated for study. Their vulnerability to diverse forms of injury
      (FeSO4-induced oxidant stress, hypoxia, Ca2+ ionophore, cytochalasin D, PLA2) was
      compared to that found in normal PTS. Post-glycerol PTS manifested significant
      resistance to each insult (decreased lactate dehydrogenase +/- N-acetyl-beta-D
      glucosaminidase release). Protection against FeSO4 was virtually complete and it
      was associated with a 50% decrease in membrane lipid peroxidation. No decrease in
      hydroxyl radical generation was noted during the FeSO4 challenge (salicylate trap
      assessment), suggesting a primary increase in membrane resistance to attack. That
      PLA2 addition caused less deacylation, plasma membrane enzyme (alanine
      aminopeptidase) release, and LDH leakage from post-glycerol versus normal tubules
      supported this hypothesis. To test whether cytoresistance was specifically
      triggered by heme proteins (vs. being a non-specific filtered protein effect, or
      a result of endotoxin cascade activation), rats were injected with purified
      myoglobin, non-heme containing filterable proteins, or endotoxin. Only myoglobin
      induced cytoresistance. In vivo heme oxygenase inhibition (tin-protoporphyrin)
      did not block the emergence of cytoresistance and it was expressed despite Na,K
      ATPase inhibition (ouabain) or cytoskeletal disruption (cytochalasin D). In vivo
      heat shock failed to protect. In conclusion, (1) rhabdomyolysis induces broad
      based proximal tubular cytoresistance; (2) heme proteinuria is its trigger; and
      (3) it is most easily explained by a primary increase in plasma membrane
      resistance to attack.

PMID- 7637264
TI  - Gentamicin activates rat mesangial cells. A role for platelet activating factor.
AB  - Gentamicin-induced decreases in glomerular filtration rate have been associated
      with a marked decline in the glomerular capillary ultrafiltration coefficient
      which could be mediated by mesangial cell contraction or release of vasoactive
      hormones. We studied the effect of gentamicin on mesangial cells proliferation,
      contraction and Ca2+ mobilization. Moreover, we attempted to assess a possible
      role of platelet activating factor (PAF) as a mediator of the observed effects of
      gentamicin on mesangial cells. Gentamicin induced a reduction of planar surface
      area of cultured rat mesangial cells that was blunted by the PAF-antagonist, BN
      52021. Gentamicin induced an increase in [Ca2+]i that was inhibited by BN-52021.
      Gentamicin also stimulated [3H]thymidine incorporation into DNA, an effect that
      was also reduced by BN-52021, and by other two structurally different PAF
      receptor antagonists: alprazolam and BB-823. Gentamicin induced c-fos mRNA
      expression in quiescent mesangial cells. Gentamicin stimulated the synthesis and
      release of PAF in cultured rat mesangial cells. The present studies demonstrate
      that gentamicin activates mesangial cell function. These actions seem to be
      mediated, at least in part, by PAF synthesis and release.

PMID- 7637265
TI  - IL-1 beta regulates rat mesangial cyclooxygenase II gene expression by tyrosine
      phosphorylation.
AB  - The pro-inflammatory cytokine, interleukin-1 beta, induces the mRNA for
      prostaglandin endoperoxide synthase II gene in renal mesangial cells. This
      inductive effect is selective for prostaglandin endoperoxide synthase II and not
      prostaglandin endoperoxide synthase I. In the present experiments IL-1 beta
      increased COX II mRNA, and this was inhibited by genistein and herbimycin A, both
      inhibitors of protein tyrosine kinases. The dose dependent effect of genistein on
      inhibition of mRNA for COX II correlated with the inhibition of the release of
      PGE2 into the media. Induction of COX II by interleukin-1 beta was mimicked by
      incubating the cells in the presence of a protein tyrosine phosphatase inhibitor,
      vanadate. These experiments also illustrate selective induction of COX II mRNA
      without induction of COX I mRNA. Western analysis utilizing antiphosphotyrosine
      antibodies demonstrated in whole lysates of mesangial cells treated with
      interleukin-1 beta that the transient phosphorylation of several proteins
      occurred. Interleukin-1 beta induced the transient phosphorylation of a protein
      of about 39/40 kD. Similarly, vanadate also produced a rapid and transient
      phosphorylation of a protein of about 39/40 kD in addition to other proteins.
      Immunoprecipitation of mesangial cell lysates with agarose conjugated
      antiphosphotyrosine antibody and Western analysis of precipitated proteins with
      anti-ERK2 antibody demonstrate that the 39/40 kD protein phosphorylated on
      tyrosine is ERK2 and suggests participation of one of the MAP kinase family of
      extracellular receptor kinases in IL-1 beta stimulated induction of the COX II
      gene.

PMID- 7637266
TI  - Utility of intra-access pressure monitoring in detecting and correcting venous
      outlet stenoses prior to thrombosis.
AB  - Vascular access thrombosis is a major problem for hemodialysis patients. Over
      7.75 years, we performed intra-access venous pressure monitoring at zero dialyzer
      blood flow (VP0), correlated VP0 with access anatomy angiographically, and
      examined the effect of two levels of stenosis, 50% and > 65% luminal diameter
      reduction (% D) as selection criteria for referral and elective angioplasty or
      surgical revision upon access outcomes. Summary receiver outcome curves for
      absolute intra-access pressure (VP0) and intra-access pressure normalized for
      systemic pressure (VP0/systolic BP) were constructed to evaluate sensitivity and
      specificity and compared to recirculation and duplex color-flow Doppler. Access
      outcomes included thrombosis, revision, replacement, and angioplasty rates that
      were normalized per 100 patient years (100 pt-yrs). During the 7.75 year long
      study period totaling 832 patient-access years of risk, the percentage of
      prosthetic bridge grafts increased from 65% to 80%. SROC showed better
      sensitivity for normalized (VP0/systolic BP) than absolute intra-access pressure
      (VP0) in grafts. Recirculation had poor predictive power in prosthetic bridge
      grafts compared to VP0. Predictive power of recirculation was superior to VP0 in
      native arteriovenous fistulae. The angioplasty rate correlated inversely with the
      degree of luminal reduction used as selection criterion for referral for
      angioplasty or surgical revision. A strong inverse relationship between
      thrombosis rate and the angioplasty rate (R2 = 0.99) but not between thrombosis
      rate and the number of angiograms performed (R2 = 0.39) was noted. A consistent,
      yet evolving, intensive graft maintenance protocol produced a 70% decrease in the
      thrombosis rate, a 79% decrease in the access replacement rate, and an increase
      in the average age of patent usable vascular accesses from 1.97 to 2.98 years
      that was associated with a 13-fold increase in the angioplasty rate. We conclude
      that vascular access monitoring with VP0/systolic BP provides excellent selection
      criteria for angiographic referral. Intervention for stenotic lesions > 50% D
      using angioplasty or surgical revision markedly reduces thrombosis and access
      replacement rates.

PMID- 7637267
TI  - Insulin-like growth factor-I gene expression in the tibial epiphyseal growth
      plate of growth hormone-treated uremic rats.
AB  - To identify the molecular mechanisms involved in long bone growth of uremic
      animals, we evaluated the effects of recombinant human growth hormone (rhGH)
      supplementation on whole body growth, growth plate morphometrics, and insulin
      like growth factor-I (IGF-I) gene expression in the tibial epiphyseal growth
      plates of uremic rats. Uremia was induced by a two-stage subtotal nephrectomy
      (Nx) of 30-day-old rats, followed by rhGH (N = 6) or saline (N = 6) treatment
      from day 56 to day 70 of age. Controls (N = 4) were sham decapsulated. Treatment
      with rhGH on Nx animals caused: (1) a significant increase in weight, (2)
      longitudinal growth similar to controls, and (3) increased total growth plate
      width predominantly due to an increase in hypertrophic zone width. rhGH increased
      IGF-I mRNA abundance in both zones, but the increase was greater in the
      proliferative zone. These changes were accompanied by concomitant alterations in
      IGF-I immunoreactivity. In uremic animals, therefore, rhGH treatment induces
      local IGF-I gene expression in the growth plate and increases the hypertrophic
      zone width but not the proliferative zone width. The latter suggests resistance
      to IGF-I action in that zone.

PMID- 7637268
TI  - Favorable course of steroid-responsive nephrotic children with mild initial
      attack.
AB  - The course and prognosis of idiopathic nephrotic syndrome has thus far not been
      found to be predicted from the severity of the manifestations at the onset. Among
      66 steroid-responsive nephrotic children, eight were asymptomatic without edema
      and identified by chance proteinuria on a urinary screening program. The
      selectivity index for proteinuria (a clearance ratio of IgG to transferrin) was
      0.10 or less in all of the five children examined. All of the eight children
      responded quickly to the prednisolone therapy. Grades of proteinuria and
      hypoalbuminemia were lower in the asymptomatic children than in the symptomatic
      children who presented with edema. Median proteinuria levels were 2.0 versus 4.2
      g/day/m2 (P < 0.01), respectively, and mean serum albumin levels were 2.2 +/- 0.3
      versus 1.8 +/- 0.4 g/dl (mean +/- SD; P < 0.01), respectively. None of the eight
      asymptomatic children relapsed for at least one year after completion of the
      prednisolone treatment, while, in contrast, 30 of 58 symptomatic nephrotic
      children relapsed during the same one-year period (P < 0.01). These findings
      suggest that, among steroid-responsive nephrotic children, those with mild
      manifestations without edema may have a milder disease and show an extremely
      favorable clinical course.

PMID- 7637269
TI  - Effects of chronic treatment with angiotensin converting enzyme inhibitor or an
      angiotensin receptor antagonist in two-kidney, one-clip hypertensive rats.
AB  - The effects of chronic angiotensin II (Ang II) receptor blockade (losartan) or
      converting enzyme inhibition (enalapril) on blood pressure (BP), urinary albumin
      excretion (Ualb V), renal histology and the hemodynamic and excretory function of
      the clipped and nonclipped kidneys were studied in two-kidney, one-clip (2-K 1-C)
      rats. One day after clipping the right renal artery, male Wistar rats were
      divided into three groups receiving: (1) losartan, 20 mg/kg/day (N = 7), (2)
      enalapril, 20 mg/kg/day (N = 8), or (3) no treatment (controls, N = 9) for three
      weeks. Both losartan and enalapril treatments maintained conscious BP at
      comparably lowered levels compared to control animals (116 +/- 6 mm Hg and 113 +/
      2 mm Hg vs. 188 +/- 11 mm Hg, respectively, P < 0.01). Treatment also prevented
      the increase in Ualb V, observed for the untreated group, three weeks after
      clipping (1.7 +/- 0.5 and 0.7 +/- 0.1 mg/24 hr vs. 17.8 +/- 7 mg/24 hr,
      respectively, P < 0.01). After three weeks of treatment, acute study of renal
      function during pentobarbital anesthesia revealed higher values of GFR and RPF
      and lowered vascular resistance for nonclipped kidneys from the losartan and
      enalapril groups compared to the corresponding kidneys from control animals.
      Despite the lower BP of both treated groups, clipped kidney GFR and RPF were
      unchanged compared to the control group. Ualb V for nonclipped kidneys from
      untreated rats was approximately 5- to 10-fold higher than in the nonclipped
      kidneys from the treated groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7637270
TI  - Efficacy and tolerance of alpha-2b interferon therapy on HCV infection of
      hemodialyzed patients.
AB  - A high frequency (25%) of anti-hepatitis C virus (HCV) antibodies is observed in
      French hemodialyzed patients; this is associated with detectable viremia in 85%
      and results in chronic hepatitis in more than 90%. We conducted a pilot study to
      examine the tolerance and efficacy of alpha-2b Interferon therapy upon HCV
      infection in hemodialyzed patients. Nineteen anti-HCV positive hemodialyzed
      patients were given a standard alpha-2b interferon regimen (3 megaunits
      subcutaneously three times weekly, following each hemodialysis) over six months
      as a treatment of biopsy-proven chronic hepatitis (N = 16) or acute hepatitis (N
      = 3). Thirteen of these 19 had increased levels of aminotransferase at the time
      of treatment. Serum HCV RNA was tested qualitatively and quantitatively by the
      polymerase chain reaction and the bDNA test, respectively, at the beginning and
      at the end of antiviral treatment, and a third time at least six months after the
      end of therapy (mean follow-up 18 +/- 9 months). HCV genotype was determined in
      the 15 patients who had detectable HCV RNA before treatment. The biological
      response (long-term response, relapse or non-response) was defined as usual
      according to the serum aminotransferase levels during therapy and at least six
      months after. A post-treatment liver biopsy, allowing comparison with
      semiquantitative pathological scores, was performed in 14 patients. Only one of
      the 19 treated patients did not complete therapy because of poor tolerance, while
      18 of the 19 fairly tolerated a complete six month course of alpha-2b
      interferon.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7637271
TI  - Familial hypomagnesemia with hypercalciuria and nephrocalcinosis.
AB  - Very few patients with familial hypomagnesemia, hypercalciuria and
      nephrocalcinosis have been described. Information about clinical course, familial
      studies or evolution after renal transplantation is very scant. We have studied
      eight patients with this syndrome who belong to five different families. The mean
      age at diagnosis was 15 +/- 7 years (5 to 25 years). The primary clinical data
      were polyuria-polydipsia (8 cases), ocular abnormalities (5), recurrent urinary
      tract infections (5) and recurrent renal colics with stone passage (2). Bilateral
      nephrocalcinosis was observed in all cases. Every patient showed hypomagnesemia
      (1.1 +/- 0.2 mg/dl) with inappropriately high urinary magnesium (Mg) excretions
      (70 +/- 17 mg/day), Mg clearances (4.4 +/- 1.2 ml/m) and Mg fractional excretions
      (16.2 +/- 7.1%). Hypercalciuria was present in every case except in those with
      advanced renal insufficiency. Serum parathormone levels were abnormally high.
      Serum calcium (Ca), phosphorus and potassium, and urinary excretions of uric acid
      and oxalate were normal. Neither chronic oral Mg administration nor thiazide
      diuretics normalized serum Mg levels or urinary Ca excretions, respectively.
      Follow-up was 6 +/- 4.5 years. Renal function worsened in every case with six
      patients starting on chronic dialysis after 4.3 +/- 3.8 years. The progression
      rate of renal insufficiency correlated with the severity of nephrocalcinosis.
      Five patients have received a kidney graft, and their serum Mg and urinary Ca
      have always been within normal values after transplantation. Twenty-six members
      of four of the affected families were studied: none of them showed
      hypomagnesemia, renal insufficiency or nephrocalcinosis. However, eleven cases
      (42%) had hypercalciuria and four of them presented with recurrent renal stones.
      Two family members had medullary sponge kidneys. In conclusion, progression to
      renal insufficiency is common in this syndrome; oral Mg and thiazide diuretics
      are ineffective to correct abnormalities. After kidney graft, tubular handling of
      Mg and Ca was normal. A striking incidence (42%) of hypercalciuria was found in
      the familial study.

PMID- 7637273
TI  - Effect of hemodialysis on cardiovascular rhythms in end-stage renal failure.
AB  - The purpose of this investigation was to determine non-invasively the alteration
      in autonomic cardiovascular control observed in end-stage renal disease (ESRD)
      patients submitted to a hemodialysis (HD) treatment. The effect of HD on finger
      blood pressure (BP) and heart rate (HR) variability was studied by means of
      spectral analysis in 12 ESRD patients at supine and during 45 degrees head-up
      tilt. Amplitude spectra of BP and HR rhythmicity were estimated and integrated
      amplitudes of the low (60 to 140 mHz, Mayer waves) and high frequency (area under
      the curve at mean respiration rate +/- 50 mHz) components were computed. The
      overall variability of a signal was given by the total area under the curve of
      the spectrum between 20 and 500 mHz. The transfer function was calculated between
      systolic BP and HR fluctuations using cross-spectral analysis. The principle
      findings are as follows: (1) Before HD, overall variability in systolic and
      diastolic BP as well as in the low frequency component in BP spectra were
      markedly reduced in ESRD patients compared to control subjects. Dialysis produced
      an immediate improvement in overall BP variability and the LF BP rhythmicity. (2)
      Before HD, there was an alteration of the HR spectral profile in uremic patients.
      (3) Chronic uremia and HD induced no changes in the transfer gain characteristic
      of modulation of HR by systolic BP. Taken together, these findings suggest that
      volume depletion in ESRD patients during a dialysis treatment is responsible for
      the improvement of overall BP variability and its spectral components.

PMID- 7637274
TI  - An estimate of beta 2-microglobulin deposition rate in uremic patients on
      hemodialysis using a mathematical kinetic model.

PMID- 7637272
TI  - Bone disease in predialysis, hemodialysis, and CAPD patients: evidence of a
      better bone response to PTH.
AB  - The spectrum of bone disease in predialysis and dialysis patients has changed
      during the last decade. The incidence of aplastic bone disease has increased and
      this can not be attributed to bone aluminum deposition; moreover, low bone
      cellular activity is present despite a moderate elevation in PTH levels. This
      study compares PTH levels and types of bone disease in both predialysis and
      dialysis patients from the same geographical area. We prospectively studied 119
      unselected end-stage renal disease patients: 38 were immediately predialysis
      (PreD), 49 on hemodialysis (HD), and 32 on CAPD. A bone biopsy was performed in
      all patients. Aplastic bone disease with < 5% bone surface aluminum was a common
      finding (48%, 32%, and 48%, in PreD, HD, and CAPD, respectively). In all groups,
      an intact PTH level below 120 pg/ml was highly predictive of low bone turnover.
      Conversely, a PTH level above 450 pg/ml was always associated with histologic
      features of hyperparathyroid bone disease. Among the bone histomorphometric
      parameters, osteoblast surface showed the best correlation with intact PTH in
      each group, and the slope of the regression line for this correlation was
      significantly steeper in HD and CAPD than PreD patients. Thus, the range of PTH
      (95% confidence limit bands) needed to obtain a normal osteoblast surface of 1.5%
      was greater in preD than in HD and CAPD patients (300 to 500 vs. 75 to 260 pg/ml,
      respectively). In all groups some degree of marrow fibrosis was observed when PTH
      levels were greater than 250 pg/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7637276
TI  - Nonimmunologic causes of late renal graft loss.

PMID- 7637277
TI  - [The use of thoracoscopy in patients with a pleural exudate].
AB  - The results of cytologic, histologic and visual studies of pleural bioptate are
      presented. It is expedient to hospitalize the patients with the pleural exudate
      syndrome in the surgical department of phthisiopulmonologic profile.

PMID- 7637275
TI  - Transport of phosphorothioate oligonucleotides in kidney: implications for
      molecular therapy.
AB  - The systemic administration of phosphorothioated antisense oligonucleotides has
      been demonstrated to be an effective strategy for the control of gene expression.
      Because previous studies have suggested both hepatic and renal accumulation of
      systemically administered oligonucleotides, we explored whether the kidney might
      be a site of free DNA transport. [32P]-phosphorothioate oligonucleotides (20
      mers) were excreted in urine but cleared at only 30% of glomerular filtration
      rate. Plasma clearance of the label was very rapid (t1/2 approximately 5 min) but
      the half life of labeled S-deoxynucleotide excreted in urine was much slower (28
      min). Infused oligonucleotide appeared in urine with little degradation. By
      autoradiography of renal tissue, labeled antisense oligonucleotides appeared
      within Bowman's capsule and the proximal tubule lumen. DNA was detected in
      association with brush border membrane and within tubular epithelial cells. Brush
      border membrane preparations from rat kidney contained oligonucleotide binding
      proteins as determined by gel mobility shift and UV cross linking assays. Because
      renal epithelial cells efficiently take up phosphorothioate oligonucleotides
      without apparent degradation, the kidney appears to be an excellent target for
      site-directed antisense therapy, but may be a site of antisense toxicity as well.

PMID- 7637278
TI  - [Intrapleural hemorrhage in closed chest trauma].
AB  - Four hundred and thirty nine sufferers were treated for closed thoracic trauma.
      Of them, 39 (8.9%) were operated on. Drainage of the pleural cavity was performed
      in 78 (17.7%) patients. In 2.1% of cases, clotted hemothorax was diagnosed. In 5
      patients, thoracoscopic destruction of the clotted hemothorax was performed
      according to original technique. All the patients recovered.

PMID- 7637279
TI  - [A new sorbent used for preparing the intestines for a surgical intervention].
AB  - A new sorbent with a high sorptive capacity and antimicrobial properties against
      different species of microorganisms (aerobic and anaerobic) is suggested. Its
      effectiveness has been proved both in vitro and in vivo. The authors consider
      that the sorbent can be recommended for clinical trials with the aim of its use
      in preparation of the intestine for the operation.

PMID- 7637281
TI  - [The functional characteristics of the cardiovascular and respiratory systems in
      respiratory failure in patients with disseminated fibrous-cavernous pulmonary
      tuberculosis].
AB  - Resulting from complex preoperative clinico-functional examination of the 50
      patients with generalized fibro-cavernous pulmonary tuberculosis, it was
      established that inclusion of compensatory mechanisms of the cardiovascular and
      respiratory systems was due to the development of chronic failure. Direction,
      pronouncement and interrelation of the main parameters of external respiration,
      oxygen transport and hemodynamics are determined by a degree of hypoxia.

PMID- 7637280
TI  - [The use of laser radiation in the treatment of complicated chest trauma].
AB  - The results of treatment of 84 sufferers with a complicated thoracic trauma,
      using irradiation of the YAG-neodymium, argon, helium-neon and arsenide-gallium
      lasers, are presented. The techniques for the use of lasers for photocoagulation
      of defects of the lung and thoracic wall through a thoracoscope, endobronchial
      laser therapy and laser puncture is described. The expediency to use laser
      irradiation in the complex of treatment of a complicated thoracic trauma is
      shown.

PMID- 7637282
TI  - [The diagnosis and surgical treatment of neck tumors].
AB  - On the basis of the analysis of the results of diagnosis and treatment of 319
      patients with a tumour of the neck, sequence of the use of a complex of
      diagnostic methods, including puncture biopsy, has been substantiated. The
      results of subsequent histologic and cytologic study of a biopsy specimen in 89%
      of the patients coincided with the findings of a postoperative histologic study
      of the tissue removed.

PMID- 7637283
TI  - [Changes in the immunological indices of patients with obstructive jaundice and
      liver cirrhosis during the extracorporeal connection of a pig spleen].
AB  - The immunologic indices were studied in 29 patients with hepatic cirrhosis and
      obstructive jaundice, who had the porcine spleen been connected according to the
      conventional technique, and in 17 patients of the control group. The blood was
      collected in dynamics. The positive effect of the method on the immune status of
      the patients, which manifested itself in activation of a T-link of immunity,
      normalization of the indices of B-link, decrease in the severity of intoxication
      due to elimination of the middle molecular mass peptides and circulating immune
      complexes, was noted.

PMID- 7637285
TI  - [Methods for the prevention and treatment of acholia].
AB  - In the clinic, the special appliances and apparatus for collection of the bile,
      its filtration, sterilization and introduction into the stomach of a patient were
      developed and used in patients with external biliary fistula. Since 1987, the
      original method for treatment of the alcoholic disease has been introduced. It
      was used in 40 patients.

PMID- 7637284
TI  - [The correction of disorders of the rheological properties of the blood in
      pancreatitis].
AB  - In 20 patients operated on for acute pancreatitis, the blood plasma viscosity,
      aggregative characteristics of erythrocytes and thrombocytes were studied after
      the operation. Effectiveness of inclusion into the complex of treatment of
      corrigative therapy, therapeutic plasmapheresis and plasmosorption is shown.

PMID- 7637286
TI  - [The diagnostic and therapeutic potentials of thoracoscopy in thoracic surgery].
AB  - Within a decade, the authors performed 484 thoracoscopies in patients with
      spontaneous pneumothorax, open and closed thoracic trauma, pleuritis, pleural
      empyema. High diagnostic possibilities of the method permitted to choose a
      rational therapeutic tactics. In 228 cases, different endothoracic interventions
      under the guidance of a thoracoscope were performed. With the use of
      thoracoscopy, diathermocoagulation, laser and ultrasound irradiation were
      performed, medical glue was introduced. This permitted in most cases to eliminate
      intrapleural injuries and achieve stable smoothing of a lung.

PMID- 7637287
TI  - [Methods for treating chronic coprostasis].
AB  - The indications for choice of a method for treatment of chronic colonic stasis
      have been developed. Use of direct, transrectal electrostimulation of the colon
      with simultaneous recording of mechanoelectrocolograms was effective in 85% of
      the patients. Intraoperative definition of a level of colonic resection
      contributed to prevention of the development of long-term disease recurrence.

PMID- 7637288
TI  - [The efficacy of the clinical use of the preparation Cifran in treating surgical
      infection].
AB  - The results of the use of antibacterial preparation "Cifran" in patients with
      purulent-inflammatory processes of different genesis and location were studied. A
      good tolerance of the patients to the preparation was established. High
      chemotherapeutic effectiveness of the preparation in detection of gram-positive,
      gram-negative and anaerobic microflora was noted.

PMID- 7637289
TI  - [Ogilvie's syndrome in surgical patients].
AB  - On the basis of the analysis of observation of 24 patients, the causes and
      mechanisms of the Ogilvie syndrome development after the operation were studied.
      The incidence of occurrence of the syndrome in 1615 patients with acute ileus has
      been established. Its clinical forms, methods for diagnosis and treatment were
      studied.

PMID- 7637290
TI  - [Stomach injury].
AB  - The results of treatment of 221 patients with injury to a stomach (IS), whose age
      range was from 3.5 to 71 years, have been analysed. Closed IS was noted in 9
      (4.1%), open--in 212 (95,9%), isolated--38.5%. The main method of operative
      treatment (in 92.8% of sufferers) was the organ closure. Surgical errors were
      made in 9.5% of the patients. The postoperative complications occurred in 75
      (33.9%) sufferers. Total lethality was 11.8%. A good long-term result of
      treatment was noted in 48.0%, a satisfactory one--in 45.2%, an unsatisfactory one
      -6.8% patients.

PMID- 7637292
TI  - [The mineralization of the regenerate and the hormonal regulation of bone
      formation during the treatment of a malunited diaphyseal fracture of the shin
      bones].
AB  - In 68 patients with imperfectly united fracture of the crural bones who underwent
      treatment with the use of the Ilizarov's method, the processes of mineralization
      of the osseous regenerate being formed were studied. The most rapid deposition of
      the mineral substances was noted in gradual elimination of a deformity. In
      shortening of an extremity, the rate of mineralization depended on a size of the
      elongation performed. Increase in content of the osteotropic hormones and cyclic.
      nucleotides was indicative of the presence of favourable conditions for formation
      of osseous regenerate in correction of angular deformity by means of the
      Ilizarov's method.

PMID- 7637291
TI  - [The treatment of chronic anteromedial knee joint instability].
AB  - The results of surgical treatment of the anterior median instability in more than
      500 patients are presented. The surgical methods and technique of the original
      methods for the treatment of I-IV degree disease are described. The long-term
      results of treatment of 376 patients have been studied. In 327 of them, the
      result is good.

PMID- 7637293
TI  - [The clinical significance of a combination of dysplastic scoliosis with
      hemostatic system disorders].
AB  - Examined were 74 patients ranging in age from 6 to 48 years with dysplastic
      scoliosis. Disorders in the system of hemostasis were revealed in 67 patients.
      Including the 25 operated ones. The operative blood loss of more than 20 % of the
      circulating blood volume was noted 2 times more often in patients with the
      disorders in the system of hemostasis, mainly with the VIII factor deficiency.
      Intravenous administration of a cryoprecipitate contributed to restoration of the
      normal VIII factor level and more than 2-fold decrease in operative blood loss.

PMID- 7637295
TI  - [Circular resection of the trachea].
AB  - The results of treatment of 75 patients operated on for different diseases of the
      trachea are summarized. In 51 patients, a combined circular or figured defect of
      the larynx and trachea, in 12--defect of the cervicothoracic portion of the
      trachea, in 12--that of bifurcation of the trachea was reconstructed.
      Postoperative lethality was 4,2%. The death of the patients was caused by
      arrosive bleeding from the brachiocephalic trunk.

PMID- 7637296
TI  - [The diagnosis and treatment of acute nondestructive appendicitis].

PMID- 7637294
TI  - [The effect of low-intensity laser radiation on the regional hemodynamics in
      strangulated intestinal obstruction].
AB  - In the experiment on 214 white rats, the effect of different types of low
      intensive laser irradiation and existing methods of treatment on regional
      hemodynamics in strangulated ileus was studied. Combined use of ultraviolet and
      helium-neon lasers has to be proved to be the most effective. Ultraviolet laser
      irradiation contributed to increase in elasticity of the arterial wall and
      cupping off the vascular spasm, helium-neon irradiation had a stimulating effect
      on the tissues of the intestinal wall.

PMID- 7637297
TI  - [Stenosis of the large intestine as a complication of pancreatitis].

PMID- 7637298
TI  - [The validation of the use of endolymphatic infusion in intensive therapy].

PMID- 7637299
TI  - [A rapid method for the intraoperative control of the hermetic sealing of a large
      intestine anastomosis].

PMID- 7637300
TI  - [A method for forming an invagination esophagojejunal anastomosis].

PMID- 7637301
TI  - [A combination of giant hemangioma of the liver and duodenal ulcer].

PMID- 7637302
TI  - [The characteristics of juvenile duodenal ulcer].

PMID- 7637303
TI  - [The type of surgical intervention in patients with duodenal peptic ulcer
      depending on the trypsin-inhibitor activity of the blood serum].

PMID- 7637304
TI  - [The prognosis of duodenal peptic ulcer complications in marine transport
      workers].

PMID- 7637305
TI  - [Results of using progressive intraocular lenses].
AB  - Results of one-year follow-up of 25 eyes with "Progress 3" progressive
      intraocular lenses produced by Domilens (France) are presented. Visual acuity for
      long distance was 1.0 without correction in 92% of cases for short distance 0.75
      to 0.5 in 84%. Among the few and minor complications, none were connected with
      the applied lenses.

PMID- 7637306
TI  - [Acute ischemic optic neuropathy].
AB  - The authors presented a case of a woman, 78, with anterior ischaemic optic
      neuropathy--presumed Horton's disease. During 3 weeks before the patient was
      referred to the clinic, she had complained of strong head-, jaw- and ear-ache,
      bad general feeling and decreased appetite. At this time the patient was examined
      by a neurologist, a laryngologist and an internist, who did not find any
      pathology. The aim of this paper is to take into consideration the importance of
      early diagnosis in acute ischaemic optic neuropathy, especially that of arteritic
      etiology, which very often leads to blindness. This disastrous course could be
      avoided by early applied steroid therapy.

PMID- 7637307
TI  - [A case of glioma of the optic nerve with a 12-year follow-up observation].
AB  - Clinical course of the case of a now 20 patient, with glioma of the optic nerve,
      removed 12 years ago, is presented. The tumour was removed with a intraorbital
      part of the optic nerve, but the eyeball was saved, what enabled the normal,
      symmetrical development of the child's face. Painful atrophy of the eyeball
      occurred 10 years after surgery and it seems that there will be a necessity to
      remove the eye.

PMID- 7637308
TI  - [A problem with the histopathologic diagnosis of optic nerve glioma. A case
      report].
AB  - The methods and results of histopathological and immunohistochemical
      investigation of an optic nerve tumour removed in a 6-year girl are presented.
      The difficulties were connected with a proper differential diagnosis between
      schwannoma and astrocytoma.

PMID- 7637309
TI  - [Marshall syndrome--case report].
AB  - A girl, 15, with Marshall syndrome, was hospitalized for retinal tear and
      detachment of the left eye. The results of ophthalmological examination and
      applied eye surgery have been described. The authors confirm the essential
      phenotypical overlap of Marshall and Stickler syndromes. This suggest that they
      are caused by variable expression of a differently mutated gene, probably the
      type II procollagen gene (COL2A1), known to play a part in the etiology of
      Stickler syndrome. This justifies the usage, by some authors, of the common name
      of Marshall-Stickler syndrome.

PMID- 7637310
TI  - [A case of necrotic scleromalacia during the course of rheumatoid arthritis].
AB  - Necrotic scleromalacia occurred in both eyes of patient, 80, with rheumatoid
      arthritis lasting for 00 years. The authors report the clinical course of the
      disease during a 2.5 year follow-up, methods of treatment and compared their own
      observations with those of others.

PMID- 7637311
TI  - [Genetics of congenital color vision defects. I. Common types of color
      blindness].
AB  - Normal human colour vision is based on the presence of 3 kinds of cones
      containing 3 different visual pigments, sensitive to short (blue), middle (green)
      and long (red) wavelengths. Congenital defects of colour vision are based on
      handicap or total loss of these pigments' function, usually a result of changes
      in their coding genes. The common types of colour blindness, referred to red
      green axis, are present in about 8% of males and 0.44% of females. 3/4 of them
      are deuteranopes or deuteranomalous trichromats and 1/4 of them are protanopes or
      protanomalous trichromats. All of them are inherited in X-linked recessive way.
      The genes have been already mapped and sequenced. The cause of the great majority
      of their changes is nonhomologous recombination, which produces a gene deletion
      or creates the red-green or green-red hybrid genes. The result of that is the
      production of visual pigment with partly or totally changed spectral sensitivity.

PMID- 7637312
TI  - [Genetics of congenital color vision defects. II. Rare types of color blindness].
AB  - Between the rare types of colour blindness, the known best are defects of blue
      colour vision, which are called tritanopia or trinanomaly (tritanomalous
      trichromacy). Their incidence is 1 in 500 and they are inherited in autosomal
      dominant way with incomplete penetrance. The basis of them are mutations of the
      short (blue) wavelength sensitive visual pigment gene. The gene has been mapped
      on the chromosome 7 and has already been cloned and sequenced. However, the loci
      heterogeneity should not be excluded in that condition. Another rare type of
      colour blindness in blue cone monochromacy. It is based on the cone sensitivity
      to short (blue) wavelength only. The condition is inherited in X-linked recessive
      way and it is known, that it can be caused by 2 different mechanisms. The first
      one--two-step pathway--consists of green cone pigment gene deletion, and point
      mutation of red cone pigment gene. The second one--one-step pathway--arose by
      deletion of regulatory sequence of both genes of visual pigments, mapped on the X
      chromosome. Different types of total and partial achromatopsia are also
      described. The best known ones are: rod monochromacy, which is inherited in
      autosomal recessive way and consist of rod vision only, and cone dystrophy,
      usually inherited in X-linked recessive way.

PMID- 7637313
TI  - [Current views on the etiopathogenesis of proliferative vitreoretinopathy].
AB  - Review of current knowledge concerning the etiology and factors associated with
      development and clinical course of PVR is presented. Special attention was paid
      to the role of blood-retinal barrier break and iatrogenic factors. The new
      conception that PVR could be compared with "wound healing" reaction, in which
      autoimmunological mechanisms were involved is also discussed.

PMID- 7637314
TI  - [Evaluation of new intraocular lenses in a scanning microscope].
AB  - New posterior chamber lenses produced by 6 different companies, 3 from each, were
      examined in a Novoscan 30 scanning microscope. Practically in each lens
      irregularities of the surface of the haptic part were found and in many of them
      also in the optic part. The relatively smallest irregularities were observed in
      the lenses of the companies (in alphabetical order): Alcon, Domilens and Storz.

PMID- 7637315
TI  - [Changes in the visual system of patients with carotid artery occlusion].
AB  - The authors presented results of visual system examination in 28 persons in whom
      disturbances of blood flow in carotid arteries were diagnosed with colour doppler
      ultrasonography. The patients underwent routine ophthalmological examination,
      including kinetic and static perimetry. Ocular signs only, with no neurological
      changes, were found in 46% of patients. In 21% of cases there were episodes of
      transient blindness; homonymous hemianopsia occurred in 10%, acute ischaemic
      optic neuropathy in 11%, and secondary neovascular glaucoma in 14% of patients.

PMID- 7637316
TI  - Tumor stroma as a regulator of neoplastic behavior. Agonistic and antagonistic
      elements embedded in the same connective tissue.

PMID- 7637317
TI  - Genetic approaches to pathogenesis of neurodegenerative diseases.

PMID- 7637318
TI  - Cortical tissue of patients with hereditary cerebral hemorrhage with amyloidosis
      (Dutch) contains various extracellular matrix deposits.
AB  - BACKGROUND: Hereditary cerebral hemorrhage with amyloidosis (Dutch) (HCHWA-D) and
      Alzheimer's disease (AD) have certain clinical and histopathologic features in
      common; both are characterized by cerebral amyloid beta deposits. Extracellular
      matrix (ECM) components have been demonstrated in plaques and in vascular amyloid
      of AD, suggesting a causative relation. EXPERIMENTAL DESIGN: We studied the
      immunohistochemical expression of the ECM components collagen type I, III, and
      IV, heparan sulfate proteoglycan (HSPG), laminin, and fibronectin in cortical
      tissue of six HCHWA-D patients, two AD patients, and five controls. RESULTS: The
      vasculature of control patients and the noncongophilic vessels in HCHWA-D and AD
      patients stained for all ECM components, with the exception of collagen type I in
      part of the capillaries. The media of normal larger vessels stained for collagen
      type I and III and fibronectin; a similar pattern was found in the vascular
      amyloid in HCHWA-D and AD patients. The plaques in HCHWA-D and AD reacted for
      HSPG and weakly for collagen III and IV and laminin. Furthermore, with the
      exception of anti-collagen type I, all anti-ECM Ab decorated coarse deposits
      clustered in the vicinity of thick-walled, amyloid-laden vessels in HCHWA-D
      patients; these deposits were not spatially related to amyloid beta-positive
      plaques. CONCLUSIONS: This study demonstrates the presence of ECM components in
      the main pathologic features of HCHWA-D and as perivascular deposits. The
      observed distribution of matrix molecules is partly different from AD. The ECM
      may well be essential for the evolvement of the pathology of HCHWA-D.

PMID- 7637319
TI  - The presence and subtype of Epstein-Barr virus in B and T cell lymphomas of the
      sino-nasal region from the Osaka and Okinawa districts of Japan.
AB  - BACKGROUND: Association between Epstein-Barr virus (EBV) and human malignancies,
      including sino-nasal lymphoma (SNL), has been suggested. EBV-associated
      malignancies have been reported to show distinct geographic distribution.
      EXPERIMENTAL DESIGN: In the present study, the presence of an EBV genome and its
      subtypes (type A and B) were examined in 52 cases of sino-nasal lymphomas of B
      and T cell type collected from two areas of Japan: Osaka, situated on the
      mainland, and Okinawa, islands situated in a southwest part of Japan with a
      subtropical climate. Our previous epidemiologic study showed that the frequency
      of nasal T cell lymphoma was 3.5 times higher in Okinawa than in Osaka. RESULTS:
      There were no prominent differences in age distribution or sex ratio between
      these two areas: age ranged 8 to 85 (median 54) years, with a male to female
      ratio of 1.26:1. Immunophenotypically, 27 cases were B cell type (20 Osaka, 7
      Okinawa), 20 were T cell type (9 Osaka, 11 Okinawa), and 5 were undefined. By
      PCR, EBV positivity in throat washings of normal individuals in Osaka and Okinawa
      was 52 and 53%, respectively, with marked preponderance of subtype A in both
      areas. EBV genome was found in 6 of 15 cases (40%) and 4 of 5 cases (80%) of
      nasal B and T cell lymphomas in Osaka and in 3 of 7 cases (43%) and 7 of 7 cases
      (100%) in Okinawa, showing the different frequencies of positivity by
      immunophenotype but not by district. All but one patient had type A EBV. The in
      situ hybridization confirmed the results of PCR as positive signals in the
      nucleus of proliferating cells. Latent membrane protein-1 was expressed in 13 of
      22 cases (59%). CONCLUSIONS: These findings suggest that EBV, exclusively type A,
      might be a causative factor in sino-nasal lymphoma of not only T cell but also B
      cell type in Japan.

PMID- 7637320
TI  - Expression of proteolytic cathepsins B, D, and L in periodontal gingival
      fibroblasts and tissues.
AB  - BACKGROUND: A major feature of gingivitis and periodontitis is the destruction of
      the collagenous matrix of the surrounding connective tissue. The hypothesis that
      proteolytic enzymes release from cells adjacent to the site of destruction was
      recently supported by the presence of increased levels of cathepsin B, D, and L
      in the gingival crevicular fluid of patients suffering from periodontal disease
      (PD). EXPERIMENTAL DESIGN: We studied the expression of mRNA of cathepsins B,D,
      and L in early passaged, adherent gingival fibroblasts of patients with chronic
      adult PD. In addition, we examined the presence of cathepsin D and L mRNA
      expressing cells in periodontal tissue specimen by in situ hybridization, and we
      localized the respective enzymes by immunohistochemistry. RESULTS: Strong gene
      expression of the three cathepsin types could be detected by dot hybridization in
      all PD-derived gingival cells. Immunohistochemical distribution of cathepsins and
      mRNA for cathepsin D and L could be demonstrated mainly in PD tissue specimen,
      largely in the area in between the epithelium and the adjacent subepithelial
      connective tissue. Examination of the cell types revealed multiple macrophage-
      and fibroblast-shaped cells expressing positive staining for cathepsins.
      CONCLUSIONS: The present data support the the concept that cathepsins play a
      major role in tissue destruction and may represent a target for therapeutic
      interventions.

PMID- 7637322
TI  - Neurofibromin: expression by normal human keratinocytes in vivo and in vitro and
      in epidermal malignancies.
AB  - BACKGROUND: Neurofibromin is the product of the NF1 gene, the mutations of which
      have been linked with type 1 neurofibromatosis. The expression of neurofibromin
      in human skin has not been analyzed in detail. EXPERIMENTAL DESIGN: Polyclonal Ab
      were raised against synthetic peptides corresponding to three different sites of
      neurofibromin. One of the Ab selectively recognized type II neurofibromin. The
      localization of neurofibromin was first studied in normal human skin. Further
      studies concentrated on neurofibromin expression in basal cell and squamous cell
      carcinomas. Reverse transcription-PCR (RT-PCR) and molecular hybridizations and
      immunocytochemistry were used to characterize the expression of neurofibromin in
      cultured keratinocytes. RESULTS: All neurofibromin-specific Ab immunolabeled the
      epidermis. The basal keratinocytes displayed the most prominent immunosignal for
      type II neurofibromin. RT-PCR demonstrated the presence of both type I and II
      neurofibromin mRNA transcripts in cultured keratinocytes. Keratinocytes induced
      to differentiate and to arrest division by a high (1.4 mM) Ca2+ concentration of
      the culture medium displayed a down-regulation of neurofibromin expression at the
      mRNA and protein levels. This was most strikingly demonstrated by a reduction of
      immunoreactivity for type II neurofibromin. Basal cell carcinomas displayed a
      weak immunosignal for type II neurofibromin. In contrast, particularly the
      central areas of squamous cell carcinoma, islands were intensely immunolabeled.
      CONCLUSIONS: The results suggest that neurofibromin acts as a regulator of the
      basal keratinocytes in normal skin and that cultured keratinocytes offer a human
      model for studies aimed to elucidate the regulation of neurofibromin gene
      expression. Furthermore, aberrations in neurofibromin expression may play a role
      in the pathogenesis of epidermal cancers.

PMID- 7637321
TI  - Expression and prognostic significance of TGF-beta isotypes, latent TGF-beta 1
      binding protein, TGF-beta type I and type II receptors, and endoglin in normal
      ovary and ovarian neoplasms.
AB  - BACKGROUND: The etiology and biology of ovarian carcinogenesis is largely
      unknown. Recent results have indicated prognostic significance of growth factors
      in this malignancy. TGF-beta is a widely distributed growth factor with
      multifactorial effects in in vitro systems. Studies on the in vivo expression
      pattern of TGF-beta and its receptors might help us to understand its biologic
      significance in this malignancy. EXPERIMENTAL DESIGN: Tissue samples of normal
      ovary and benign as well as malignant ovarian neoplasms were examined for
      expression of transforming growth factor (TGF)-beta 1, -beta 2, and -beta 3, the
      latent TGF-beta-binding protein (LTBP), TGF-beta type I (T beta R-II) receptors
      and endoglin by immunohistochemistry and in situ hybridization. Furthermore, the
      results of the immunohistochemical analysis were compared with patient survival.
      RESULTS: Expression of all ligands was significantly increased in tumor cells
      compared with the normal epithelial cells. In contrast, LTBP immunoreactivity was
      detected significantly more often in normal epithelium than in tumor cells. T
      beta R-I and T beta R-II as well as endoglin were found in tumor tissues and
      normal ovary without any difference among the groups. In the blood vessels of
      malignant tumors, significantly increased TGF-beta 1 reactivity and decreased TGF
      beta 2 reactivity were found when they were compared with those of normal ovaries
      and benign tumors. Patients with malignant tumors expressing TGF-beta 1, T beta R
      I, or endoglin in blood vessels demonstrated longer survival than those having
      negatively stained tumors. In contrast, positive endoglin staining in tumor cells
      correlated with decreased survival even in advanced disease or in patients having
      residual tumor bulk after surgery. CONCLUSIONS: The differential expression of
      TGF-beta ligand and the significant correlations between expression of ligands or
      receptors and patient survival indicate involvement of the TGF-beta system in
      ovarian tumor development.

PMID- 7637323
TI  - Expression cloning of the cDNA encoding a melanoma-associated Ag recognized by
      mAb HMB-45. Identification as melanocyte-specific Pmel 17 cDNA.
AB  - BACKGROUND: mAb HMB-45 recognizes a melanocyte lineage-associated Ag present in
      "activated melanocytes" and malignant melanoma cells. Despite its important
      practical significance in diagnostic pathology and its potential role as an
      "activation marker" of melanocytic cells, the HMB-45-reactive Ag remained
      undefined. Molecular characterization of the HMB-45-reactive Ag may help in
      analyzing underlying mechanisms of melanocyte activation and melanoma tumor
      progression. EXPERIMENTAL DESIGN: A cDNA library constructed from the HMB-45
      immunoreactive human melanoma cell line SK-MEL-28 was screened for expression of
      the cDNA encoding the HMB-45-reactive protein. Screening was performed by
      expression in COS-7 cells and subsequent immunocytochemical screening.
      Correlation between HMB-45 immunoreactivity and mRNA expression of the cloned
      cDNA was analyzed by antisense mRNA expression in HMB-45-immunoreactive SK-Mel-28
      cells, by Northern blot hybridization, and by comparative immunohistochemistry
      and in situ hybridization. RESULTS: A cDNA clone encoding the HMB-45-reactive Ag
      was isolated and shown to be homologous to the Pmel 17 cDNA. Expression of either
      HMB-45 or Pmel 17 cDNA in COS-7 cells induced cytoplasmic HMB-45 immunoreactivity
      as described for melanoma cells. Conversely, constitutional HMB-45 immunoreaction
      in SK-MEL-28 cells could be markedly reduced by expression of antisense Pmel 17
      RNA. In several tissues, Pmel 17 mRNA content conformed to the known expression
      pattern of HMB-45-reactive Ag. Comparative in situ hybridization and
      immunohistochemistry demonstrated a consistent co-localization of Pmel 17
      transcripts and HMB-45-reactive Ag at the cellular level, with strong expression
      in "activated" melanocytes and melanoma cells and significantly less expression
      in normal adult melanocytes. CONCLUSIONS: We conclude that Pmel 17 cDNA encodes
      the HMB-45-reactive Ag. Pmel 17 has been postulated to be involved in melanin
      synthesis and expression of melanoma-peptide epitopes recognized by CTLs.
      Differential expression of Pmel 17/HMB-45 may have considerable effects in the
      stepwise process of melanoma progression by aberrant pigment formation and
      expression of CTL-reactive epitopes.

PMID- 7637324
TI  - Differential expression of collagen types I, II, III, and X in human osteophytes.
AB  - BACKGROUND: Osteophytes are neoplastic cartilaginous and osseous protrusions
      growing at the margins of osteoarthritic joints. Their formation involves complex
      patterns of cellular proliferation, differentiation, as well as matrix synthesis
      and turnover that are poorly understood. EXPERIMENTAL DESIGN: Here we report on
      an experimental approach using in situ hybridization and immunohistology to
      elucidate pathways of chrondrocyte differentiation in human osteophytes. Ab and
      cDNA probes for collagen types were used as specific parameters for chondrocyte
      phenotypes. RESULTS: In early precartilaginous mesenchymal tissue, cytoplasmic
      mRNA for alpha 1(I) and alpha 1(III) collagen genes (Col1A1 and Col3A1) were
      found by in situ hybridization, correlating with the distribution of type I and
      III collagen as revealed by Ab staining. Strong expression of type II collagen
      both at mRNA and protein levels was the hallmark of chondrogenic differentiation
      in the cartilaginous zone of osteophytes. Type II collagen expression increased
      in all cartilaginous and fibrocartilaginous areas with growth and maturation of
      osteophytes. The signal intensity obtained after in situ hybridization with a
      COL2A1 probe was high and corresponded to that obtained in fetal cartilage,
      whereas normal adult articular cartilage usually did not show measurable type II
      collagen expression. In fibrocartilaginous areas, the most abundant, but
      heterogeneous tissue type seen in osteophytes, type II and III collagen mRNA
      expression overlapped considerably. Type III collagen was scattered, both
      pericellularly and interterritorially, over the whole osteophyte, excluding bone
      and chondrocytic cells of the deep zone. The strongest type I collagen expression
      was seen in bone and in the superficial fibrous layer. In areas of endochondral
      ossification, large chondrocytes were found expressing type X collagen, a
      specific marker for hypertrophic chondrocytes. CONCLUSIONS: These results show
      that discrete stages of cartilage differentiation can be precisely followed in
      osteophytes using collagen type-specific cDNA probes and Ab as markers. In
      addition, a fibrocartilaginous chondrocyte phenotype was identified that
      expresses type II and III, but not type I collagen.

PMID- 7637325
TI  - Expression of smooth muscle myosin isoforms in urinary bladder smooth muscle
      during hypertrophy and regression.
AB  - BACKGROUND: Partial ligation of the urinary out-flow tract of rabbit bladder
      induces hypertrophy of the smooth muscle layer in the bladder wall, and it is
      reversible by the removal of the ligature. The expression of smooth muscle myosin
      heavy chain isoforms SM1 and SM2 after hypertrophy and the regression of
      hypertrophy (reversal) was investigated at the translational and transcriptional
      levels using this experimental model. DESIGN: The contractile activity of smooth
      muscle strips derived from normal, hypertrophied, and reversal bladders was
      measured using electrical stimulation. Expression of SM1 and SM2 in normal,
      hypertrophied, and reversal muscle tissue was characterized using SDS-PAGE,
      reverse transcriptase-PCR (RT-PCR), and RNase protection assay. RESULTS: Smooth
      muscle strips from hypertrophied urinary bladder revealed a decrease in both
      force and rate of force generation in response to field stimulation. These
      alterations in contractility were reversed by removal of the obstruction. The
      altered function in bladder hypertrophy was also associated with changes in
      translation and transcription of the smooth muscle heavy chain isoforms SM1 and
      SM2. Upon regression of the hypertrophy by removal of the obstruction, the
      relative ratio of myosin heavy chain SM2:SM1 returned to nearly normal values.
      Analyses by RT-PCR showed a decrease in the mRNA transcript for SM2 in
      hypertrophied bladder muscle; and, on reversal of the hypertrophy, the SM2 mRNA
      level returned to that of normal bladder. These data suggest that the obstruction
      induced hypertrophy activates a down-regulating mechanism for the expression of
      myosin SM2 heavy chain. CONCLUSIONS: Obstruction-induced alteration in the
      contractile characteristics of the urinary bladder smooth muscle is associated
      with changes in the expression of smooth muscle myosin heavy chains at both the
      protein and mRNA levels. The contractile function and the myosin heavy chain
      expression return to normal after regression of the smooth muscle hypertrophy on
      removal of the obstruction.

PMID- 7637326
TI  - In situ analysis of cytokine responses in experimental murine schistosomiasis.
AB  - BACKGROUND: Infection with schistosomiasis results in CD4+ T helper (Th) cell
      dependent granulomatous inflammation around parasite eggs. T cell-derived
      cytokines play a critical role in the induction and subsequent down-modulation of
      the granulomas. These cytokine responses have been previously examined in
      lymphoid cell supernatants or in tissue homogenates but have not been examined
      directly in the local microenvironment of the lesions or in the reacting lymphoid
      tissues. EXPERIMENTAL DESIGN: With the use of specific mAb, the cytokines IL-2,
      IFN gamma, IL-4, and IL-10 were investigated by direct immunocytochemical
      analysis in situ in hepatic egg granulomas and lymphoid organs from acutely and
      chronically infected mice. Cytokine expression in situ was compared with cytokine
      production during a secondary response in vitro. RESULTS: All cytokines examined
      were detected in various amounts in both the hepatic egg granulomas as well as in
      mesenteric lymph nodes and spleen. The majority of cells expressing the cytokines
      was found in lymph nodes, and very few were found in granulomas. Relatively small
      numbers of granulomas contained most of the cytokine-expressing cells, which
      tended to localize in their periphery. Granulomas and lymphoid organs in the
      acute disease contained significantly more cytokine-expressing cells in
      comparison with those from the chronic disease. This observation correlated well
      with cytokine production in vitro. CONCLUSIONS: Direct immunocytochemical
      examination in situ was used to detect and measure cytokine-producing cells in
      hepatic egg granulomas and reacting lymphoid organs of acute and chronic
      experimental murine schistosomiasis. Observed cytokine patterns suggest that
      granulomas contain T lymphocytes of both the Th-1 and Th-2 types and that
      cytokine production occurs during a limited time in the early granuloma. The
      immunocytochemical technique affords a direct appraisal of amount, dynamics, and
      localization of cytokine-producing cells in the unperturbed local environment.

PMID- 7637327
TI  - Protein analysis of human maculae in relation to age-related maculopathy.
AB  - BACKGROUND: Age-related maculopathy (ARM) is the most common cause of blindness
      in the elderly in the western world. Its early stage is characterized by many
      histopathologic changes, including two extracellular deposits, basal laminar
      deposit (BLD) and drusen. The origin and chemical composition of BLD and drusen
      are unknown and are considered to be important in the development of ARM, so we
      analyzed proteins in human macular tissue associated with ARM. EXPERIMENTAL
      DESIGN: Homogenized macular extracts of 15 human eyes with ARM and 10 age-matched
      control eyes were examined by two-dimensional electrophoresis. The proteins in
      the gels were silver-stained, and the obtained protein patterns were analyzed by
      a computer-imaging system. RESULTS: Five glycoproteins were specifically present
      in human maculae with ARM (p = 0.0009). One of the spots was characterized by
      sequence analysis as haptoglobin beta-chain, and another had a high homology with
      a part of the interphotoreceptor retinoid-binding protein precursor. However, the
      100% matching of the latter was not statistically significant because we could
      only sequence eight amino acids of this protein. CONCLUSIONS: The known
      association between haptoglobin beta-chain and atherosclerosis and the increase
      of this glycoprotein in human maculae with ARM supports the recently described
      relationship between atherosclerosis and ARM found in an epidemiologic study.
      Furthermore, the neovascular growth-stimulating properties of haptoglobin warrant
      further research into haptoglobin as a possible inducing agent of late stages of
      ARM.

PMID- 7637328
TI  - Proliferation, cell death, and neuronal differentiation in transplanted human
      embryonal carcinoma (NTera2) cells depend on the graft site in nude and severe
      combined immunodeficient mice.
AB  - BACKGROUND: Embryonal carcinoma cell lines have been used to study the induction
      and progression of tumors, the mechanisms governing lineage commitment in the
      central nervous system, and the developmental biology of neurons and glia. Here,
      we have used a human embryonal carcinoma cell line (NTera2/cl.D1 or NT2 cells)
      that resembles neural progenitor cells to study how an in vivo environment
      influences and regulates the fate of these cells. EXPERIMENTAL DESIGN: To
      understand the mechanisms that coordinately regulate the proliferation, death,
      and differentiation of NT2 cells, we examined these processes by transplanting
      human NT2 cells in the brains and peripheral tissues (liver, muscle) of
      immunodeficient mice. RESULTS: We demonstrate that the proliferation,
      differentiation, and death of NT2 cells were modulated by the anatomical site
      into which the NT2 grafts were implanted. The NT2 cells continued to proliferate
      and undergo cell death but showed a very limited capacity to differentiate into
      neurons after implantation into the subarachnoid space and superficial neocortex.
      At this site, the NT2 cell grafts rapidly formed bulky tumors that were lethal
      within 70 days postimplantation. Further, NT2 cell grafts in the lateral
      ventricles, liver, and muscle behaved in a similar manner. In contrast, NT2 cells
      implanted into the caudoputamen ceased proliferating and showed no evidence of
      necrosis or apoptosis after postimplantation survival intervals of more than 20
      weeks. This occurred in parallel with the progressive differentiation of large
      numbers of NT2 cells into postmitotic, immature, neuron-like cells. CONCLUSIONS:
      These results suggest that signal molecules or other "cues" (e.g., cell-cell
      contacts) capable of regulating the proliferation, death, and differentiation of
      human NT2 cells are biologically active in the adult mouse caudoputamen. Thus,
      the transplantation of human NT2 cells into the central nervous system of
      immunodeficient mice may serve as an in vivo model system for studies of the
      formation and re-modeling of the developing central nervous system.

PMID- 7637329
TI  - Inflammatory polyarthritis induced by mercuric chloride in the Brown Norway rat.
AB  - BACKGROUND: Mercuric chloride (HgCl2) induces an autoimmune syndrome in
      susceptible strains of rodent. In the Brown Norway (BN) rat, this is
      characterized by autoreactive T cells, high levels of total IgE, IgG
      autoantibodies, including anti-collagen types I and II, and tissue injury,
      including glomerulonephropathy and necrotizing vasculitis of the gut. The high
      total IgE levels and evidence showing ex vivo down-regulation of IFN gamma and in
      vivo up-regulation of IL-4 suggest that HgCl2-induced autoimmunity occurs in a
      Th2 lymphokine environment. EXPERIMENTAL DESIGN: HgCl2-autoimmunity was induced
      in BN rats using standard methods. Anti-collagen (types I and II) Ab and IgG
      subclasses were measured by ELISA. Arthritis was scored on Days 13 to 17 after
      HgCl2 treatment. Ankle joints and synovium were examined with standard histologic
      and immunohistochemical techniques. The incidence and severity of arthritis were
      compared in normal and R73 (anti-alpha/beta T cell receptor mAb)-treated BN rats.
      After R73 treatment, T cell function was assessed by measuring the total IgE and
      anti-type II collagen response to HgCl2, and FACS was used to assess the number
      of peripheral blood OX19+ lymphocytes (T cell marker). RESULTS: A self-limiting
      inflammatory arthritis develops in more than 82% of animals and is more severe in
      males. Histologically, there is a predominant ED1+ macrophage synovial
      infiltrate, areas of fibrinoid necrosis, and vasculitis and erosions of
      cartilage. The peak anti-collagen (type I and II) Ab titer does not correlate
      with arthritis incidence or severity. Treatment with R73 markedly reduces the
      rise in total IgE and IgG anti-type II collagen, reduces OX19+ peripheral blood
      lymphocytes, and abolishes the arthritis. CONCLUSIONS: HgCl2 induces a T cell
      dependent inflammatory arthritis in the BN rat. In contrast with other animal
      models, HgCl2-induced arthritis is associated with an apparent Th2 lymphokine
      response.

PMID- 7637330
TI  - Development of renal podocytes cultured under medium perifusion.
AB  - BACKGROUND: In the past, podocytes have been described as highly susceptible to
      dedifferentiation under cell culture. Whether this process resulted from
      insufficient culture conditions or whether it was a consequence of missing
      cellular interactions remained unclear. A further reason could be that podocytes
      within the maturing kidney are irreversibly growth-arrested at a very early point
      of development because proliferating cells have been detected at the S-shaped
      body stage but not at the capillary loop stage or in the maturing glomeruli.
      These were important reasons that hindered the establishment of podocyte cell
      culture systems. EXPERIMENTAL DESIGN: The aim of our present study was to culture
      podocytes under the most organotypic conditions possible to maintain typical
      cellular characteristics. Cortex explants of neonatal rabbit kidneys consisting
      of nephrogenic tissue were used as a source for podocytes. No serum additives
      were given for the whole culture period of 13 days. An organ-specific environment
      was obtained by keeping the podocytes within the surrounding renal tissue and by
      ensuring a permanent exchange of medium. RESULTS: mAb were used to characterize
      podocytes and the other glomerular cell types. Cultured podocytes and parietal
      cells of Bowman's capsule were identified by EnPo 1. Ks 19.2.105, a marker for
      cytokeratin 19, was used to discriminate among these epithelial cells because
      cytokeratin 19 is expressed by the parietal cells of Bowman's capsule but not by
      podocytes. The Ab EC1 specifically detected endothelial cells. Glomerular
      endothelium cultured under medium perifusion expressed these typical Ag and thus
      could be unequivocally discriminated. Furthermore, by means of the proliferation
      marker Ki-67, it could be demonstrated that glomerulus-like structures developed
      under culture by proliferation of visceral and parietal cells of Bowman's
      capsule. CONCLUSIONS: A culture model is presented that allows the maintenance of
      developing podocytes within the organ-specific tissue environment and under
      permanent medium perifusion.

PMID- 7637331
TI  - Immunostaining for prostate cancer androgen receptor in paraffin identifies a
      subset of men with a poor prognosis.
AB  - BACKGROUND: Knowledge of androgen receptor (AR) content could help predict
      hormone response and disease course in prostate cancer. However, determination of
      AR by biochemical assay is difficult. An immunohistochemical assay (ICA) would
      solve most difficulties and be especially useful if it could be performed on
      paraffinized tissue. EXPERIMENTAL DESIGN: AR was studied in paraffin sections
      from 90 men for whom endocrine response, survival (except one case), and/or
      biochemical AR was known. After Ag retrieval in a microwave oven, a polyclonal
      anti-AR Ab was used with the peroxidase antiperoxidase method. Results were
      semiquantified using a Histoscore (Hscore) and were correlated with biochemistry,
      endocrine response, and survival. RESULTS: Only 15 patients were AR-negative. AR
      ICA did not correlate with biochemistry, Gleason score, stage, or ethnicity but
      did correlate with endocrine response and survival. The average Histoscore was
      significantly lower in patients with progressive disease (p < 0.05). In a Cox's
      regression analysis of survival (mean follow-up = 30 months) AR-ICA was a
      significant predictor (p = 0.015). Risk of death was 2.5 times greater for a
      patient with a negative assay compared with one with a positive result.
      CONCLUSIONS: Our data indicate that AR status by ICA may be a useful predictor of
      survival and endocrine response in prostate cancer. Further studies are needed to
      confirm these results because the assay could impact significantly on management.

PMID- 7637332
TI  - Youth risk behavior surveillance--United States, 1993.
AB  - Priority health risk behaviors that contribute to the leading causes of
      mortality, morbidity, and social problems among youth and adults often are
      established during youth, extend into adulthood, and are interrelated. The Youth
      Risk Behavior Surveillance System (YRBSS) monitors six categories of priority
      health risk behaviors among youth and youth adults: behaviors that contribute to
      unintentional and intentional injuries, tobacco use, alcohol and other drug use,
      sexual behaviors, dietary behaviors, and physical activity. The YRBSS includes a
      national, school-based survey conducted by CDC and state and local school-based
      surveys conducted by state and local education agencies. This report summarizes
      results from the national survey, 24 state surveys, and nine local surveys
      conducted among high school students during February through May 1993. In the
      United States, 72% of all deaths among school-age youth and young adults are from
      four causes: motor vehicle crashes, other intentional injuries, homicide, and
      suicide. Results from the 1993 YRBSS suggest many high school students practice
      behaviors that may increase their likelihood of death from these four causes:
      19.1% rarely or never use a safety belt, 35.3% had ridden during the 30 days
      preceding the survey with a driver who had been drinking alcohol, 22.1% had
      carried a weapon during the 30 days preceding the survey, 80.9% ever drank
      alcohol, 32.8% ever used marijuana, and 8.6% had attempted suicide during the 12
      months preceding the survey. Substantial morbidity and social problems among
      adolescents also result from unintended pregnancies and sexually transmitted
      diseases including HIV infection.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7637333
TI  - Development and dissemination of a manual to promote teacher preservice in health
      education.
AB  - Teacher preparation at the preservice level plays an important role in ensuring
      implementation of comprehensive school health education in the classroom. This
      article describes development and dissemination of a resource manual to provide
      college instructors with materials that support a health education course for
      teacher education majors. A statewide survey was administered to instructors one
      year following distribution to examine the dissemination and use of the resource
      manual. Results suggest provision and dissemination of model materials for
      preservice education provides an acceptable and feasible step toward curricular
      change in teacher preservice training in health education. Increased use of the
      manual was associated with attendance at a training workshop.

PMID- 7637334
TI  - A statewide institute to deliver professional development programs to school
      health personnel in Massachusetts.
AB  - Schoolchildren suffer from health problems ranging from chronic medical and
      developmental problems to new morbidities related to drugs, violence, and sexual
      behavior. To help administrators, teachers, and health personnel meet the new
      challenges in schools, nursing educators from the University of Massachusetts and
      Simmons College developed the UMass-Simmons School Health Institute. The
      Institute delivers a series of professional development programs in all regions
      of the commonwealth to: 1) devise innovative strategies to remove health barriers
      to learning and to promote the health of children and adolescents, and 2) enhance
      the design, implementation, integration, and management of comprehensive school
      health programs, including those mandated and regulated by the Commonwealth of
      Massachusetts. This article describes a statewide model to prepare school health
      personnel for delivery of comprehensive school health services.

PMID- 7637335
TI  - Student opinions of condom distribution at a Denver, Colorado, high school.
AB  - Over the past two decades, the reported number of women and men who have had
      intercourse by age 18 has increased by approximately 20%. Concomitant increases
      occurred in the incidence of teen-age pregnancies and sexually transmitted
      diseases (STDs), including HIV. Increasing condom availability within schools has
      been proposed as one means of preventing the serious potential consequences of
      unprotected sexual intercourse. Although published surveys report 68% to 75% of
      adults have supported distributing condoms in schools, little is known about what
      students think about making condoms available at school. In this survey, high
      school students in Denver initiated and helped conduct a school-wide survey to
      assess student opinions about condom distribution in their school. Of 931 high
      school students responding to the survey, 85% replied that condoms should be
      distributed in their school, and 76% believed making condoms more accessible
      would not change the frequency of sexual activity among teens.

PMID- 7637336
TI  - An assessment of 23 selected school-based sexuality education curricula.
AB  - While quality sexuality education curricula are available, those responsible for
      selecting a curriculum may not feel confident to choose one to meet the needs of
      their students and community. This paper presents a method to guide in selecting
      sexuality education curricula as well as results from an evaluation of 23 school
      based sexuality education curricula. School administrators, curriculum
      specialists, health educators, school nurses, teachers, and parents involved in
      curriculum adoption or development can use the process described to select or
      develop a sexuality education curriculum to meet the needs of their school and
      community.

PMID- 7637337
TI  - Pertussis update.

PMID- 7637338
TI  - Effect of protein intake on tumor growth and cell cycle kinetics.
AB  - Previous research has documented significant acceleration of tumor growth in
      animals receiving short-term parenteral nutrition. This study was performed to
      determine the effect of long-term enteral protein intake on tumor cell cycle
      kinetics in the tumor-bearing host. Fifty Lewis/Wistar rats with subcutaneous
      mammary tumor implants (AC-33) were randomized to receive a standard protein diet
      (22.0% protein; 4.20 kcal/g) or protein-depleted diet (0.03% protein; 4.27
      kcal/g). Animals were sacrificed after 7 or 14 days on each diet and tumor
      cytokinetics determined by flow cytometry. Tumor volume was significantly reduced
      in animals receiving the protein-depleted versus standard protein diet after 14
      days (P < 0.01). No difference was found in tumor cell cycle kinetics (% G0/G1,
      S, or G2/M populations) or tumor growth fraction (S + G2/M) in animals receiving
      standard or protein-depleted diet after 7 or 14 days. These results suggest that
      reduced tumor growth with prolonged protein depletion in this model occurs by
      either (a) movement of tumor cells from the active cell cycle to the dormant G0
      state or (b) uniform increase of cell cycle duration without changing the
      relative proportion of cells throughout the cell cycle. The potential therapeutic
      implications of nutrient-induced alterations in tumor growth are discussed.

PMID- 7637339
TI  - Fractionated irradiation of the regenerated rat liver.
AB  - Fractionated radiation therapy after liver resection for metastatic cancer has
      traditionally been a palliative procedure. Here, we consider that radiation may
      be an appropriate adjuvant therapy for cure after liver resection for metastases.
      This pilot study in rats establishes a model for evaluating the effects of
      fractionated irradiation posthepatectomy. Sixty Sprague-Dawley rats were
      randomized to four groups. The groups underwent laparotomy, laparotomy and
      radiation, hepatectomy, and hepatectomy and radiation. We found that the rats
      treated with radiation had statistically significant (P < 0.0001) clinical
      radiation change by liver function tests at 6 months. This damage was resolved to
      normal at 1 year regardless of hepatectomy. In fact, we demonstrate the
      possibility of a protective effect from radiation damage in the regenerated
      liver. We also demonstrate statistically significant histologic change at 8
      months (P < 0.01) in the radiation-treated rats which does not resolve at 1 year.

PMID- 7637340
TI  - Activation of hepatic glutaminase in the endotoxin-treated rat.
AB  - The basis for the accelerated hepatic utilization of glutamine that occurs during
      endotoxemia was investigated. In rats treated with Escherichia coli
      lipopolysaccharide, glutaminase activity, measured in membranes of freezed-thawed
      liver mitochondria, was unchanged compared with that of controls. However, flux
      through glutaminase in intact mitochondria was increased more than 3.5-fold by
      the endotoxin treatment. The effect was associated with an increase in the
      sensitivity of glutaminase flux to phosphate, an activator of the enzyme. These
      findings are similar to the activation of glutaminase by glucogenic hormones. We,
      therefore, propose that the increased hepatic consumption of glutamine during
      endotoxemia is due to an activation of glutaminase that is only evident in intact
      mitochondria.

PMID- 7637341
TI  - Dehydroepiandrosterone reduces progressive dermal ischemia caused by thermal
      injury.
AB  - Progressive ischemia and necrosis of the skin following thermal injury are
      reduced by postburn administration of the steroid hormone dehydroepiandrosterone
      (DHEA). Thermally injured animals were provided with a subcutaneous injection of
      DHEA, or a related species of steroid hormone, at various times after burning.
      During the 96 hr following administration of the scald burn, tissue necrosis was
      closely monitored. Subcutaneous administration of DHEA at approximately 1
      mg/kg/day achieved optimal protection against the development of progressive
      dermal ischemia. DHEA, 17 alpha-hydroxy-pregnenelone, 16 alpha-bromo-DHEA, and
      androstenediol each demonstrated, a similar level of protection. Other forms of
      steroids, including DHEA sulfate, androstenedione, 17 beta-estradiol, or
      dihydrotestosterone, exhibited no protective effect under the conditions tested.
      Additionally, intervention therapy with DHEA could be initiated up to 4 hr, but
      not 6 hr, after burn without a marked reduction in therapeutic benefit.
      Examination of the microvasculature of thermally injured dorsal skin suggested
      that postburn intervention with DHEA, either directly or indirectly, maintained a
      normal architecture in most of the dermal capillaries and venules within burn
      exposed tissue. These findings suggest that systemic intervention therapy of burn
      patients with DHEA or a similar acting steroid hormone may be useful in
      preventing the progressive tissue destruction caused by progressive ischemia.

PMID- 7637342
TI  - Participation of hepatic macrophages and plasma factors in endotoxin-induced
      liver injury.
AB  - The present study was designed to investigate the mechanism responsible for
      endotoxin-induced liver injury, based on the working hypothesis that hepatic
      macrophages activated by endotoxin play a key role in the development of this
      injury. At both the protein and the transcription levels, the intravenous
      administration of endotoxin was shown to have increased the capacity of hepatic
      macrophages to produce chemical mediators. To inhibit the function of hepatic
      macrophages, gadolinium chloride (GdCl3), a specific inhibitor of resident
      hepatic macrophages, was preadministered to rats before endotoxin injection.
      GdCl3 reduced the elevated glutamic oxaloacetic transamiase and lactate
      dehydrogenase serum levels produced by endotoxin treatment, suppressed the
      increased mRNA expression of tumor necrosis factor (TNF-alpha) produced in liver
      nonparenchymal cells by endotoxin, and then improved the survival rate of
      lipopolysaccharide-injected rats. These results indicated that hepatic
      macrophages played a crucial role in liver injury and that TNF-alpha was the most
      likely factor implicated in the development of endotoxin-induced liver injury.
      Furthermore, we found that liver injury did not progress during perfusion of
      endotoxin-pretreated extirpated liver with lactate Ringer's solution, whereas
      liver perfused with plasma developed remarkable hepatic impairment, which was
      inhibited almost completely by GdCl3-pretreatment; moreover, addition of heparin
      to the perfusate also prevented this deterioration. Thus, the present study
      showed that the activation of hepatic macrophages and factors in the plasma were
      two essential elements in the occurrence and development of endotoxin-induced
      liver injury.

PMID- 7637343
TI  - Phospholipase A2 in sodium taurocholate-induced experimental hemorrhagic
      pancreatitis in the rat.
AB  - We investigated the concentration of immunoreactive pancreatic phospholipase A2
      (pan-PLA2) and the catalytic activity of phospholipase A2 (CA-PLA2) in plasma,
      peritoneal fluid, and pancreas of rats in which acute hemorrhagic pancreatitis
      was induced by an intraductal injection of sodium taurocholate. The contribution
      of pancreas to the CA-PLA2 in plasma was studied by removing pancreatic PLA2 by
      absorbing plasma samples with a polyclonal antibody raised in a rabbit against
      rat pancreatic PLA2. Sodium taurocholate injected into the pancreatic duct
      produced hemorrhagic pancreatitis with necrosis and inflammatory cell invasion
      within 8 hr. Saline injection caused edematous pancreatitis, but sham operation
      did not alter pancreatic morphology from normal. The concentration of pan-PLA2
      increased rapidly in plasma in all animals, but significantly more in sodium
      taurocholate-injected animals than in saline-injected or sham-operated animals.
      The level of CA-PLA2 in plasma increased in sodium taurocholate-injected animals
      only. There was no correlation between pan-PLA2 and CA-PLA2 values in plasma in
      sodium taurocholate-injected animals. The CA-PLA2 was marginally increased in
      pancreatic tissue of sodium taurocholate-injected animals compared to that of
      saline-injected and sham-operated animals at 8 hr. Treatment by the anti-pan-PLA2
      antibody effectively removed pan-PLA2 from plasma and peritoneal fluid samples in
      sodium taurocholate-injected animals. The level of CA-PLA2 in plasma was similar
      before and after antibody treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7637344
TI  - Metabolic function of the isolated perfused rat liver in chronic sepsis.
AB  - Significant alterations of liver function have been identified in experimental
      sepsis including changes in protein and glucose production. The specific changes
      which are evident in vivo appear to depend upon the specific experimental model
      and probably represent the relative contribution of hepatocellular function and
      extrahepatic influences as well as the time course of the septic process.
      Relatively few studies have focused on function of the whole organ. In an effort
      to study intrinsic hepatic function during chronic sepsis, control and septic
      animals (intraabdominal abscess) were studied using the isolated perfused liver
      model. Basal hepatic oxygen utilization was mildly elevated compared to that in
      control livers and the oxygen consumption response to a metabolic load was found
      to be essentially identical to that in control and septic livers. Glucose and
      albumin production were not substantially different in these two groups. These
      findings suggest that alterations in liver function following the induction of
      sepsis may result from extra hepatic factors, since intrinsic liver function
      appears to be normal.

PMID- 7637345
TI  - Alpha-adrenergic receptor antagonism prevents intestinal vasoconstriction but not
      hypoperfusion following resuscitated hemorrhage.
AB  - Resuscitation (RES) after hemorrhage (HEM) results in persistent arteriolar
      constriction and hypoperfusion of the small intestine (SI) despite restoration of
      mean arterial pressure (MAP) and cardiac output (CO) to normal values. We
      postulated that increased adrenergic activity contributes to this
      vasoconstriction and impairment of flow. A loop of SI from decerebrate rats was
      exteriorized and suffused with Krebs' solution (37 degrees C, pH 7.4). In initial
      experiments, the effectiveness of alpha-adrenergic receptor antagonism by
      phentolamine (PHEN) was assessed. Subsequent groups received either topical PHEN
      (10(-6) M, n = 6) or saline (n = 6) in the suffusion and were then bled to 50%
      baseline (BL) MAP for 60 min and resuscitated to BL with shed blood/lactated
      Ringer's. Intravital microscopy and optical Doppler velocimetry were used to
      measure large (A1) and small, premucosal (A3) arteriolar diameters and RBC
      velocity; microvascular blood flow was calculated. MAP and transpulmonary CO were
      measured. During HEM, control animals developed A1 constriction and hypoperfusion
      with A3 arteriolar dilation. PHEN treatment prevented A1 constriction and
      enhanced A3 dilation but did not improve flow. Immediately after RES in controls,
      microvascular diameters and A1 flow returned to BL; however, over the 2-hr post
      RES period there was progressive A1 and A3 vasoconstriction and hypoperfusion
      despite maintenance of BL MAP and CO. After RES in PHEN-treated animals, A1 flow
      returned to BL, but progressive hypoperfusion was only partially prevented. alpha
      Adrenergic-mediated vasoconstriction contributes to intestinal hypoperfusion
      after HEM, but other mechanisms are also involved in microvascular responses
      during RES.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7637346
TI  - Peritoneal and splenic macrophage functions in the tumor-bearing host.
AB  - In the tumor-bearing host, depression of cell-mediated immunity has been well
      demonstrated, but little is known about alterations in macrophage functions. We
      hypothesized that the presence of a tumor may cause functional suppression of
      peritoneal macrophage and splenic macrophage functions, perhaps due to
      prostaglandin-E2 (PGE2) and nitric oxide. C57 BL/6 mice (n = 18) were injected
      subcutaneously with Lewis lung carcinoma 3 tumor. Control mice (n = 18) received
      no tumor and were pair-fed to intake of the tumor group. On Day 21, peritoneal
      and splenic macrophages were harvested. Cell surface Ia expression, cytotoxicity
      against P815 target cells, Candida albicans killing, and production of PGE2,
      nitric oxide, and superoxide were measured. Mean Ia expression was decreased in
      tumor animals for both peritoneal and splenic macrophages. In tumor animals PGE2
      production significantly increased in both peritoneal and splenic macrophages.
      Superoxide production significantly decreased in peritoneal macrophages but
      significantly increased in splenic macrophages. Nitric oxide production was also
      significantly depressed in tumor-bearing host peritoneal macrophages. C. albicans
      killing was significantly depressed in tumor animals' peritoneal macrophages but
      showed little change in splenic macrophages. In tumor animals cytotoxicity was
      significantly decreased in peritoneal macrophages but significantly increased in
      splenic macrophages. In the tumor-bearing host, peritoneal macrophages have
      significantly decreased accessory and effector functions. Splenic macrophages
      demonstrate decreased accessory but enhanced effector functions. PGE2,
      superoxide, and nitric oxide appear to be important mechanisms of altered
      macrophage function in the tumor-bearing host; modifying their cellular
      production may enhance host defense.

PMID- 7637347
TI  - Ischemic time-dependent microvascular changes and reperfusion injury in the rat
      small intestine.
AB  - The significance of the reperfusion period in the pathophysiology of complete
      occlusion of the intestinal circulation is controversial. Our study was designed
      to evaluate the exact magnitude of reperfusion-induced intestinal mucosal damage
      in a standardized rat model of complete segmental arterial ischemia as a function
      of the occlusion time. Intestinal ischemia was maintained for 15, 30, or 60 min,
      or ischemia was followed by a 30-min reperfusion period. Intraarterial India ink
      perfusion was applied to visualize the mucosal vascularity changes induced by
      ischemia or ischemia-reperfusion. The height of the distributing arterioles of
      the villi and the average mucosal thickness were recorded by an image analysis
      system, and the degree of mucosal damage was established on a semiquantitative 0
      to 5 grade scale. Ischemia induced erythrocyte obstructions at the villus tip, a
      progressive decrease in carbon-filled arteriole height, and a concomitant 7, 23,
      or 35% reduction of the mucosal thickness. The percentage decrease in perfused
      arteriole height/percentage mucosal thickness reduction ratio was 2.2, 1.5, or 1
      during the 15-, 30-, or 60-min ischemia, respectively. Extravasation of the
      carbon tracer was observed in the 60-min ischemia group. During reperfusion, the
      mucosal layer was reduced by 27, 38, or 57%, respectively, compared with the
      baseline values. The arteriole height reduction/mucosal thickness reduction ratio
      was 1:1 in all ischemic-reperfused groups. The degree of mucosal damage was
      significantly increased during reperfusion after the 15-min ischemia. Microvessel
      obstruction is initiated at the villus tip following the onset of arterial
      occlusion, with subsequent destruction of the surrounding tissues during
      reperfusion. The reperfusion component of the net mucosal damage may be very
      significant in early forms of complete occlusion of the mesenteric circulation.

PMID- 7637349
TI  - Pretreatment with 3,5,3'triiodo-L-thyronine (T3). Effects on myocyte contractile
      function after hypothermic cardioplegic arrest and rewarming.
AB  - Circulating levels of 3,5,3'triiodo-L-thyronine are depressed after
      cardiopulmonary bypass and have been implicated to play a contributory role in
      the alterations in left ventricular function after hypothermic cardioplegic
      arrest and rewarming. The central hypothesis of the present study was that
      pretreatment of isolated myocytes with triiodothyronine will have a direct and
      beneficial effect on contractile performance after hypothermic cardioplegic
      arrest and rewarming. Contractile function in isolated pig left ventricular
      myocytes was examined by video microscopy after the following treatment
      protocols: (1) 37 degrees C incubation in medium (normothermia) for 2 hours with
      triiodothyronine followed by a 2-hour normothermic incubation with no
      triiodothyronine, (2) 4 hours of normothermic incubation with no
      triiodothyronine, (3) normothermic incubation for 2 hours with triiodothyronine
      followed by 2 hours of hyperkalemic, hypothermic cardioplegic arrest ([K+]:24
      mmol/L; 4 degrees C) and subsequent rewarming, and (4) normothermic incubation
      for 2 hours with no triiodothyronine followed by 2 hours of hyperkalemic,
      hypothermic cardioplegic arrest and rewarming. Two hours of normothermia with
      triiodothyronine increased myocyte contractile function by 30% compared with
      values in untreated control myocytes, and this increase persisted after a
      subsequent 2-hour incubation under normothermic conditions with no
      triiodothyronine. For example, myocyte velocity of shortening in triiodothyronine
      pretreated myocytes was 84 +/- 4.9 microns/sec compared with 62 +/- 2.8
      microns/sec in control myocytes (p < 0.05). Cardioplegic arrest and subsequent
      rewarming caused a significant reduction in myocyte velocity of shortening from
      normothermic values (37 +/- 3.4 microns/sec, p < 0.05). However, in myocytes
      pretreated with triiodothyronine, myocyte contractile function was significantly
      higher after hypothermic cardioplegic arrest and rewarming (54 +/- 2.5
      microns/sec, p < 0.05). In a second series of experiments, beta-adrenergic
      responsiveness was examined after pretreatment with triiodothyronine. In the
      presence of the beta-adrenergic agonist isoproterenol (25 nmol/L), myocyte
      contractile function was increased by 26% in the triiodothyronine-treated
      myocytes compared with that in untreated control myocytes. This enhanced beta
      adrenergic responsiveness with triiodothyronine pretreatment persisted with
      subsequent exposure to hypothermic cardioplegic arrest and rewarming. In summary,
      triiodothyronine pretreatment caused an increase in myocyte contractile function
      and beta-adrenergic responsiveness under normothermic conditions and after
      hypothermic cardioplegic arrest and rewarming. Thus the present study provides
      direct evidence to suggest that preemptive treatment with triiodothyronine may
      improve left ventricular contractile performance after hypothermic cardioplegic
      arrest and rewarming.

PMID- 7637348
TI  - Adenosine pretreatment for prolonged cardiac storage. An evaluation with St.
      Thomas' Hospital and University of Wisconsin solutions.
AB  - Adenosine pretreatment has been shown to be beneficial in several models of
      ischemia-reperfusion. We wished to evaluate whether adenosine pretreatment is
      cardioprotective for prolonged cardiac storage and whether the presence of
      adenosine in the storage media affects the results. Isolated rodent hearts were
      obtained from Sprague-Dawley rats, mounted on a Langendorff apparatus,
      instrumented with an intraventricular balloon, and ventricularly paced at 300
      beats/min. Four groups of hearts were studied in a 2 x 2 factorial experiment (n
      = 8 to 12 per group). Hearts were subjected to normal perfusion or to solution
      supplemented with adenosine 50 mumol/L for 10 minutes followed by adenosine-free
      perfusion for 10 minutes. Hearts then were stored for 8 hours at 0 degrees C in
      either University of Wisconsin solution (adenosine 5 mmol/L) or St. Thomas'
      Hospital II solution (adenosine free). Adenosine pretreatment increased tissue
      levels of adenosine triphosphate before storage (p = 0.04). Nonfunction was less
      common after storage (1/19 versus 6/20 hearts, p < 0.05), and diastolic function
      was better preserved in the adenosine groups in the reperfusion phase (p = 0.01).
      The beneficial effects of adenosine pretreatment were independent of which
      storage solution was used. Developed pressure was increased (p < 0.05) and
      release of creatine kinase and lactate dehydrogenase was reduced (p < 0.0001) in
      hearts treated with University of Wisconsin solution compared with those treated
      with St. Thomas' Hospital solution. These studies suggest that adenosine
      pretreatment improves recovery after prolonged hypothermic storage and that the
      presence of adenosine in the preservation solution does not alter the results.
      The experiments provide further evidence that extended myocardial protection is
      better enhanced with University of Wisconsin solution than with St. Thomas'
      Hospital II solution.

PMID- 7637350
TI  - Intermittent aortic crossclamping prevents cumulative adenosine triphosphate
      depletion, ventricular fibrillation, and dysfunction (stunning): is it
      preconditioning?
AB  - This study was designed to determine whether intermittent warm aortic
      crossclamping induces cumulative myocardial stunning or if the myocardium becomes
      preconditioned after the first episode of ischemia in canine models in vivo. The
      role of adenosine triphosphate catabolism and subsequent release of purines on
      reperfusion-mediated postischemic ventricular dysfunction and arrhythmias was
      assessed with the use of selective inhibitors of nucleoside transport, p
      nitrobenzylthioinosine (NBMPR), and a specific adenosine deaminase inhibitor,
      erythro-9-[2-hydroxy-3-nonyl] adenine (EHNA). Thirty-two anesthetized dogs were
      instrumented to monitor left ventricular contractility, off bypass, by
      sonomicrometry. During cardiopulmonary bypass dogs were treated before ischemia
      with either saline solution (control group, n = 8) or EHNA (100 mumol/L) and
      NBMPR (25 mumol/L) (EHNA/NBMPR group, n = 8). Hearts were subjected to either 60
      minutes of global ischemia and 120 minutes of reperfusion (n = 16) or 6 episodes
      of 10 minutes of global ischemia and 10 minutes of reperfusion, followed by 60
      minutes of reperfusion (n = 16). Sixty minutes of sustained ischemia resulted in
      80% loss of adenosine triphosphate and induced reperfusion-mediated ventricular
      fibrillation and severe left ventricular dysfunction in the control group.
      EHNA/NBMPR treatment augmented myocardial adenosine trapping during ischemia,
      attenuated ventricular fibrillation, and enhanced left ventricular functional
      recovery, despite similar depletion of adenosine triphosphate (80% loss). In the
      intermittent ischemia experiment, the first episode of 10 minutes of ischemia and
      reperfusion caused significant adenosine triphosphate depletion, ventricular
      fibrillation, and left ventricular stunning in both control and drug-treated
      groups. The prevalence of ventricular fibrillation was greater in the control
      group than in the drug-treated group after the first episode of ischemia (p <
      0.05). Adenosine was the major nucleoside accumulated in the myocardium at the
      end of 10 minutes of ischemia in the EHNA/NBMPR-treated group (p < 0.05 versus
      control). Subsequent episodes of ischemia prevented ventricular fibrillation and
      did not cause cumulative left ventricular stunning in either group. Left
      ventricular function fully recovered in the EHNA/NBMPR-treated group after
      intermittent ischemia, but remained stunned in the control group. Unlike
      sustained ischemia, intermittent ischemia and reperfusion preserved myocardial
      adenosine triphosphate, limited purine release, and prevented ventricular
      fibrillation and cumulative stunning. These results suggest that intermittent
      ischemia and reperfusion augmented the endogenous protective mechanism or
      mechanisms of "preconditioning." Nucleoside trapping improved functional recovery
      after sustained or repetitive ischemia. It is concluded that adenosine
      triphosphate preservation or blockade of nucleoside transport may play an
      important role in the activation of endogenous myocardial protective mechanisms
      that "precondition" against subsequent ischemic stress.

PMID- 7637352
TI  - A randomized study of the influence of perfusion technique and pH management
      strategy in 316 patients undergoing coronary artery bypass surgery. II.
      Neurologic and cognitive outcomes.
AB  - This double-blind, randomized comparison of pulsatile or nonpulsatile perfusion
      and alpha-stat or pH-stat management during cardiopulmonary bypass was designed
      to assess postoperative central nervous system outcomes. METHODS: Neurologic and
      cognitive testing was conducted before the operation and 7 days and 2 months
      after the operation in 316 patients having coronary artery bypass and in a
      reference cohort of 40 patients having major vascular and thoracic operations.
      RESULTS: As detailed in part I of this study, mortality in patients having
      coronary bypass was 2.8%. The incidence of stroke was 2.5% and did not differ
      among bypass groups. Mortality was 2.5% for the major surgery cohort. The
      incidence of cognitive (p = 0.003) and either neurologic or cognitive dysfunction
      (p = 0.0002) was higher at 7 days for the coronary bypass group than for the
      major surgery cohort. The incidence of neurologic dysfunction remained higher (p
      = 0.050) at 2 months in the coronary bypass group. Cognitive dysfunction at 2
      months was less prevalent after 90 minutes of cardiopulmonary bypass in patients
      managed with alpha-stat than with pH-stat strategy (27% versus 44%, p = 0.047).
      CONCLUSIONS: Postoperative central nervous system dysfunction is more prevalent
      in patients having coronary bypass than in those having major operations.
      Pulsatility has no effect on central nervous system outcomes, but alpha-stat
      management is associated with a decreased incidence of cognitive dysfunction in
      patients undergoing prolonged cardiopulmonary bypass.

PMID- 7637351
TI  - A randomized study of the influence of perfusion technique and pH management
      strategy in 316 patients undergoing coronary artery bypass surgery. I. Mortality
      and cardiovascular morbidity.
AB  - The impact of perfusion technique and mode of pH management during
      cardiopulmonary bypass has not been well characterized with respect to
      postoperative cardiovascular outcome. METHODS: This double-blind, randomized
      study comparing outcomes after alpha-stat or pH-stat management and pulsatile or
      nonpulsatile perfusion during moderate hypothermic cardiopulmonary bypass was
      undertaken in 316 patients undergoing coronary artery bypass operations. RESULTS:
      Cardiovascular morbidity and mortality were not affected by pH management, and
      the incidence of stroke (2.5%) did not differ between groups. Overall in-hospital
      mortality was 2.8%, eight of the nine deaths occurring in the nonpulsatile group
      (5.1% versus 0.6%; p = 0.018). The incidence of myocardial infarction was 5.7% in
      the nonpulsatile group and 0.6% in the pulsatile group (p = 0.010), and use of
      intraaortic balloon pulsation was significantly more common in the nonpulsatile
      group (7.0% versus 1.9%; p = 0.029). The overall percentage of patients having
      major complications was also significantly higher in the nonpulsatile group
      (15.2% versus 5.7%; p = 0.006). Duration of cardiopulmonary bypass, age, and use
      of nonpulsatile perfusion all correlated significantly with adverse outcome.
      CONCLUSIONS: Use of pulsatile perfusion during cardiopulmonary bypass was
      associated with decreased incidences of myocardial infarction, death, and major
      complications.

PMID- 7637353
TI  - Video-assisted thoracic surgical resection with the neodymium:yttrium-aluminum
      garnet laser.
AB  - Since January 1991, we have performed 79 video-assisted neodymium: yttrium
      aluminum-garnet laser resections for pulmonary nodular or interstitial disease.
      Pathologic examination demonstrated malignancy in 59 patients (32 primary and 27
      metastatic), benign nodules in 11, interstitial processes in seven, and
      granulomatous disease in two. There were 39 men and 40 women with a mean age of
      63.4 +/- 12.5 years. Thirty-nine patients underwent resection with the
      neodymium:yttrium-aluminum-garnet laser alone and 40 had lesions resected with a
      combination of laser and endoscopic stapling. Laser excision was performed for
      lesions deep in the substance of the lung or on its effaced surface; both are
      locations that make stapling alone difficult. Fifteen of 32 patients with a
      diagnosis of primary lung malignancy underwent open anatomic resections.
      Pulmonary reserves of the other 17 patients were inadequate for further
      resection. Operative time, duration of chest tube placement, length of hospital
      stay, and complication rate were compared with those for 72 patients undergoing
      video-assisted thoracic surgical resection of nodules with staplers alone.
      Although operative time for laser-assisted procedures was longer (p < 0.05),
      there were no differences in duration of chest tube placement or hospital stay
      compared with stapled resections. The complication rate for laser-treated cases
      was not higher than for stapled resections and consisted primarily of air leaks
      lasting 2 to 7 days. The neodymium:yttrium-aluminum-garnet laser is a safe and
      precise primary or adjunctive tool for video-assisted thoracic surgical pulmonary
      resection.

PMID- 7637354
TI  - Lung perfusion with chemotherapy in patients with unresectable metastatic sarcoma
      to the lung or diffuse bronchioloalveolar carcinoma.
AB  - Eight patients with metastatic sarcoma to the lung (n = 4) or diffuse
      bronchioloalveolar carcinoma of the lung (n = 4) underwent isolated lung
      perfusion with chemotherapy in a pilot study. Ages ranged from 18 to 60 years and
      half were female. The left lung was perfused in three patients (single lung
      perfusion) and both lungs in five patients (total lung perfusion). Perfusions
      ranged from 45 to 60 minutes at ambient or normothermic temperatures. One patient
      received perfusion at moderate hyperthermia (40 degrees C). Escalating doses of
      doxorubicin (1 to 10 micrograms/ml perfusate) was used in six patients, whereas
      two received cisplatin (14 and 20 micrograms/ml perfusate). There were two major
      complications and no objective responses. The isolated perfusion systems gave
      excellent separation between systemic and pulmonary circulations with zero to 15%
      of the measured peak drug concentration of the pulmonary perfusate detected in
      the systemic circulation. Drug concentrations in normal lung and tumor generally
      increased with higher drug dosages and drug was detectable in mediastinal lymph
      nodes of three out of four patients in whom sampling was done. Isolated lung
      perfusion with chemotherapy can be done safely in patients with lung malignancies
      and evidence suggests that higher drug dosages should be well tolerated.

PMID- 7637355
TI  - Bronchioloalveolar carcinoma.
AB  - Bronchioloalveolar carcinoma is a subtype of adenocarcinoma of the lung with a
      relatively better prognosis. We reviewed the cases of 50 consecutive patients
      with bronchioloalveolar carcinoma treated during a 10-year period and attempted
      to analyze factors related to prognosis. During the 10-year study period, the
      prevalence of bronchioloalveolar carcinoma relative to adenocarcinoma of the lung
      remained steady. The subjects included 32 male and 18 female patients with mean
      ages of 64.7 years and 55.1 years, respectively (p = 0.0030). The preoperative
      radiographic findings included 40 cases of localized and 10 cases of diffuse
      bronchioloalveolar carcinoma. The clinicopathologic TNM staging included 20
      patients with stage I cancer, 4 with stage II cancer, 11 with stage IIIa cancer,
      3 with stage IIIb cancer, and 12 with stage IV cancer. Forty patients with
      clinical stage I, II, or III disease underwent operation (operability 80%). The
      resectability rate was 90% (36 of 40). Thirty-four procedures were considered as
      curative. The overall cumulative survival at 5 years was 22.2% (46.4% for stage
      I). Different TNM stages showed significant differences in survival time (p =
      0.0001). The median survival times were 64.6 months for stage I, 48.0 months for
      stage II, 24.7 months for stage IIIa, 9.0 months for stage IIIb, and 4.5 months
      for stage IV disease. The median survival time for localized bronchioloalveolar
      carcinoma was 27.5 months, and the median survival time for diffuse
      bronchioloalveolar carcinoma was 4.3 months (p = 0.0002). The median survival
      time for the curative resection group was 30.6 months, and the median survival
      time for the noncurative resection or nonresection group was 5.8 months (p =
      0.0001). On the basis of this study we conclude that (1) the prevalence of
      bronchioloalveolar carcinoma is quite steady, (2) bronchioloalveolar carcinoma
      presents at an earlier age in women, (3) bronchioloalveolar carcinoma frequently
      presents with lymphatic spread or systemic metastasis at diagnosis, (4) most
      localized bronchioloalveolar carcinomas are resectable and the prognosis with
      this type is better than that of the diffuse type, and (5) long-term survival
      correlates closely with initial roentgenographic appearance, TNM stage, and
      completeness of surgical resection.

PMID- 7637356
TI  - Reliable cryopreservation of trachea for one month in a new trehalose solution.
AB  - We previously reported that trehalose, a reduced disaccharide, was effective in
      the preservation of lungs. In this study, we investigated the possibility of
      prolonged cryopreservation of tracheas in a preservative solution containing
      trehalose. Five rings of cervical trachea were removed and immersed in the
      preservative solution. The harvested tracheas were then cryopreserved and stored
      in a deep freezer at -85 degrees C. One month later, five rings of mediastinal
      trachea were removed. The cryopreserved cervical tracheas were thawed and
      autotransplanted in place of the excised mediastinal trachea (n = 6). The
      anastomotic site and graft were then covered with an omental pedicle. All six
      animals survived for more than 6 months. All grafts survived without any evidence
      of atrophy or stenosis. Microscopic examination of the grafts showed that the
      integrity of the tracheal tissues was maintained. Our findings show that
      consistent cryopreservation of the trachea for 1 month is possible in a
      preservative solution containing trehalose.

PMID- 7637357
TI  - Risk analysis and long-term survival in patients undergoing extended resection of
      locally advanced lung cancer.
AB  - Although locally advanced lung cancer frequently necessitates extended resections
      to preserve a chance for cure, a higher morbidity is associated with extended
      resections. It is not known whether the increased morbidity is of relevance for
      the long-term outcome. It also remains unclear whether exclusion of certain
      patients according to their risk factors can diminish mortality in these
      patients. This study therefore investigated whether certain risk factors
      predispose patients undergoing extended pulmonary resections to increased
      morbidity or mortality. It also assessed the long-term survival. The cases of 126
      consecutive patients with locally advanced lung cancer (stage T3 or T4) were
      prospectively documented. Seventy-five percent of the patients required an
      extended resection and 25% a nonextended resection. Extended resections were
      associated with a significantly increased overall morbidity (p < 0.002). However,
      mortality, severe complications, or multiple complications were not significantly
      increased after extended resections. No risk factor predisposed to an increased
      mortality. Risk factors that were associated with particular postoperative
      complications were pathologic ergonometry (p < 0.002), a positive cardiac score
      (p < 0.003), coronary artery disease (p = 0.021), and an increased pulmonary risk
      score (p < 0.05). Overall 3-year survival was 31%. Patients undergoing extended
      resections for stage T3 or T4 tumors with no residual tumor (70% of the patients)
      showed a 3-year survival of 33%. We conclude that postoperative mortality cannot
      be reduced by excluding patients on the basis of particular risk factors from
      operations that require extended resections. If a patient is considered to be
      eligible to undergo pulmonary resection, he or she can be considered to be
      eligible to undergo extended pulmonary resection. Because prognosis is dismal in
      nonresected locally advanced lung cancer, we recommend an aggressive surgical
      approach.

PMID- 7637358
TI  - Changes in tumor necrosis factor in postpneumonectomy lung growth.
AB  - So that changes in production and binding of tumor necrosis factor-alpha during
      postpneumonectomy lung growth could be determined, rats underwent left lung
      resection and were killed 3, 7, or 14 days later, 1 hour after the injection of
      3H-thymidine. Serum was collected, and the lungs were lavaged and perfused in
      vitro. Lung volumes were measured. Lungs were homogenized, and changes in lung
      weight, protein content, deoxyribonucleic acid content, deoxyribonucleic acid
      synthesis, and tyrosine kinase activity of different lobes were recorded. Tumor
      necrosis factor-alpha content of serum, lavage fluid, and perfusate was measured
      by an enzyme-linked immunoassay. The binding of tumor necrosis factor-alpha to
      membrane extracts of lung homogenates was measured by immunoblots. Whereas the
      cardiac lobe of the remaining right lung demonstrated larger increases in size
      than other lobes after pneumonectomy, there was no difference in any growth
      parameter between it and the other lung lobes. Serum tumor necrosis factor-alpha
      was detectable in sham-operated animals and increased significantly after
      pneumonectomy. However, by day 14, it was not different from the level in sham
      operated animals. In contrast, tumor necrosis factor-alpha in lavage fluid
      remained significantly elevated, and its binding increased gradually throughout
      the study period. Tumor necrosis factor-alpha in perfusate did not demonstrate
      any rise. We conclude that lung growth after pneumonectomy is uniform among
      various lobes, which suggests that it is regulated by humoral factors. Because
      tumor necrosis factor-alpha, a cytokine known to stimulate cellular proliferation
      and matrix synthesis, is produced and bound to the lung during this process, it
      may be one of the humoral factors implicated in postpneumonectomy lung growth.

PMID- 7637359
TI  - What factors affect ventricular performance after a Fontan-type operation?
AB  - Postoperative conditions after a Fontan-type operation, particularly as they
      affect results in the early term, are thought to depend on factors such as the
      state of pulmonary circulation and ventricular function. In this study, we
      attempted to determine the factors that influence ventricular characteristics in
      the middle term after Fontan-type procedures. Catheterization was performed at a
      mean of 15 months after operation in 57 patients with univentricular
      atrioventricular connection who underwent the operation between 1.0 and 22.6
      years of age. End-diastolic volume, end-systolic volume, ejection fraction, and
      end-diastolic pressure of the systemic ventricle were analyzed together with an
      estimation of the systemic flow index. These parameters were influenced
      significantly by the presence of atrioventricular valve insufficiency. The
      morphologically left ventricle showed a better ejection fraction than did the
      morphologically right ventricle, whereas the systemic flow index was greater in
      patients undergoing total cavopulmonary connection than in those receiving an
      atriopulmonary connection. Young age was significantly associated with a better
      postoperative contractility, whereas the potential for impaired ventricular
      compliance was suggested in several patients undergoing operation after 4 years
      of age. On the basis of our results, we conclude that total cavopulmonary
      connection performed at a young age should be the surgical procedure of choice
      and that atrioventricular insufficiency must be treated properly at, and even
      after, the initial definitive repair.

PMID- 7637360
TI  - Work capacity and central hemodynamics thirteen to twenty-six years after repair
      of tetralogy of Fallot.
AB  - Exercise tests and cardiac catheterization were performed in 53 patients, 13 to
      26 years after intracardiac repair of tetralogy of Fallot. At the time of repair,
      the median age was 7 years, and 60% of patients with cyanosis had had a previous
      palliative procedure. The right ventriculotomy was closed without a patch in 21
      patients (40%), a patch restricted to the right ventricle was inserted in 18
      patients (34%), and in 14 (26%) the patch extended across the pulmonary anulus.
      At follow-up, 94% of the patients were free of symptoms. Symptom-limited work
      capacity was 87% of the predicted value (95% confidence limits, 82% to 94%). Work
      capacity was inversely related to age at follow-up, to right ventricular systolic
      pressure at rest, and to presence of moderate or severe pulmonary valve
      regurgitation. Cardiac output in relation to oxygen uptake was reduced in 74% of
      patients during exercise. In 12 patients (23%), systolic pressure at rest in the
      right ventricle was 50 mm Hg or higher. Systolic pressure during exercise in the
      right ventricle was lower in patients without a patch than in those with a patch
      and was abnormally high in all groups compared with healthy subjects. The ratio
      of right to left ventricular pressure was significantly lower than measurements
      taken immediately after repair. An intracardiac left-to-right shunt was present
      in 6 patients (11%). Three patients required invasive treatment as a result of
      our follow-up. We conclude that work capacity was moderately reduced 13 to 26
      years after repair of tetralogy of Fallot and was adversely influenced by right
      ventricular hypertension and pulmonary valve regurgitation. Intermittent lifelong
      surveillance is advocated, because patients without symptoms may have hemodynamic
      abnormalities that necessitate intervention.

PMID- 7637361
TI  - Composite and plain tubular synthetic graft conduits in right ventricle-pulmonary
      artery position: fate in growing lambs.
AB  - Our goal was to identify the most appropriate material for right ventricle
      pulmonary artery conduits in growing animals. We used 100 lambs that were 3 to 4
      weeks old (mean weight 11.7 kg). Follow-up was up to 24 months. Group I received
      plain tubular conduits: (1) Dacron knitted fabric, (2) collagen-coated knitted
      fabric, (3) Milliknit and Microknit material, (4) woven Dacron fabric, (5) three
      dimensional Dacron fabric (crossweave 500 and 800), or (6)
      polytetrafluoroethylene. Group II received either a (1) woven Dacron fabric
      conduit with a built-in tissue valve or (2) polytetrafluoroethylene graft with a
      built-in St. Jude Medical valve. We did angiograms and catheterizations every 3
      to 6 months and killed the lambs at 6, 12, 18, or 24 months. Tubular Dacron
      fabric woven or knitted grafts, regardless of matrix, pore size, thickness, or
      coating, caused formation of a thick acellular pseudointima buildup, which led to
      progressive obstruction starting as early as 3 months. Polytetrafluoroethylene
      grafts in groups I and II showed the formation of thin inner and outer capsules
      (0.5 mm) and none developed obstruction despite wall calcification. Conduits of
      woven Dacron fabric with a built-in tissue valve degenerated rapidly, leading to
      calcification thrombosis and obstruction within 3 months; no lamb survived 12
      months. Polytetrafluoroethylene conduits with a St. Jude Medical valve in lambs
      receiving anticoagulants remained free of obstruction and continued to function
      well. It appears that synthetic conduits of polytetrafluoroethylene perform well
      in either of the situations here tested and may be the best choice at present.

PMID- 7637362
TI  - The surgical anatomy of coronary venous return in hearts with isomeric atrial
      appendages.
AB  - Although absence of the coronary sinus is widely recognized in hearts with
      isomerism of the right atrial appendages, little attention has been paid to the
      fashion of the venous return from the heart itself. In this study, the
      arrangement of coronary venous return was investigated in 99 specimens with
      isomeric right and 49 with isomeric left appendages. In the normal heart, the
      coronary veins consist of a circumflex component within the atrioventricular
      groove and longitudinal components on the ventricular mass. The circumflex venous
      system was seen in 44 hearts with isomerism of left appendages (90%), but 23 of
      these hearts lacked the anatomic features of the coronary sinus. Circumflex veins
      were entirely lacking in the other 10% of hearts with isomeric left appendages
      and in all those with isomeric right appendages. In these hearts, longitudinal
      veins drained independently into the atria in three patterns. The first was a
      direct connection, with the venous orifice opening between the trabeculations of
      the atrial wall immediately having crossed the atrioventricular groove. The
      second was a crooked return, with the vein running an intramural course along the
      atrioventricular groove. The third was a distant connection, reaching superiorly
      to the smooth-walled atrial component after running an intramural course.
      Intramural courses were seen in 19% of the longitudinal veins, such veins being
      found in 62% of all hearts with no circumflex venous system. These findings,
      which to the best of our knowledge have never previously been recognized in
      detail, almost certainly have potential surgical significance.

PMID- 7637363
TI  - Left ventricular structures in atrioventricular septal defect associated with
      isomerism of atrial appendages compared with similar features with usual atrial
      arrangement.
AB  - In patients with isomeric atrial appendages, regurgitation of atrioventricular
      valves is recognized clinically as one of the risk factors that militate against
      successful achievement of definitive repairs. To determine whether this reflected
      anatomic features, we investigated 91 specimens with atrioventricular septal
      defect that had a common atrioventricular valve and biventricular
      atrioventricular connections. Of these specimens, 35 had isomeric right
      appendages, 23 showed isomeric left appendages, and 33 had usual atrial
      arrangement. We measured either the size or location of the supporting papillary
      muscles and the circumference of the mural leaflet within the morphologically
      systemic ventricle, as well as the length of outlet, inlet, and so-called scooped
      dimensions of the muscular ventricular septum. Presence of a solitary papillary
      muscle, or deviation of the attachments of the papillary muscles, was more
      frequent in hearts with isomeric right appendages. Values for the diameter and
      lengths of the papillary muscles were significantly smaller in hearts with
      isomeric right appendages compared with those with usual atrial arrangement (p <
      0.001), as were the distances between the papillary muscles (p < 0.002) and the
      circumference of the mural leaflet (p < 0.001). The proportional length of
      ventricular outlet was longer in the setting of isomeric right appendages than in
      the other groups (p < 0.001), whereas the extent of septal scooping showed no
      differences among these three groups. We conclude that these structural features
      could be factors in the known insufficiency of the common atrioventricular valve
      and the ventricular dysfunction in patients with isomeric right appendages.

PMID- 7637364
TI  - Effects of dipyridamole in combination with anticoagulant therapy on survival and
      thromboembolic events in patients with prosthetic heart valves. A meta-analysis
      of the randomized trials.
AB  - The addition of dipyridamole, an antiplatelet agent, to conventional
      anticoagulant regimens has been shown to reduce the frequency of embolization
      after valve replacement with a mechanical prosthesis. The purpose of this meta
      analysis was to reevaluate the benefit of dipyridamole by analyzing the evidence
      from all randomized clinical trials. Summary data were extracted from the
      application to the Food and Drug Administration. Six randomized clinical trials
      had accrued 1141 patients, of whom 582 received anticoagulant therapy alone and
      559 received additional dipyridamole at dosages ranging from 225 to 400 mg per
      day. The events analyzed were all thromboembolic events, both fatal and nonfatal;
      hemorrhagic events, both fatal and nonfatal; and the overall mortality. The
      combination of dipyridamole with anticoagulants reduced the risk of
      thromboembolic events (fatal or nonfatal) by 56% when compared with the use of
      anticoagulants alone (p = 0.0001). The risk reduction was seen in fatal and in
      nonfatal thromboembolic events (risk reduction for fatal events, 64%, p = 0.008;
      for nonfatal events, 50%, p = 0.005). The overall mortality rate was also
      significantly reduced by 40% in the group receiving dipyridamole (p = 0.013).
      There was no difference between treatment groups with respect to hemorrhagic
      events (risk reduction, -1%, p = 0.94). This meta-analysis supports the use of
      dipyridamole in this setting and warrants further trials with new antiplatelet
      agents.

PMID- 7637365
TI  - Modification of the maze procedure for atrial flutter and atrial fibrillation. I.
      Rationale and surgical results.
AB  - The original maze procedure that was described for the treatment of patients with
      atrial fibrillation was followed by an unacceptable incidence of two problems:
      (1) the frequent inability to generate an appropriate sinus tachycardia in
      response to maximal exercise and (2) occasional left atrial dysfunction. In an
      effort to overcome these problems, we modified the original technique (maze I)
      twice. The results of these modifications culminated in the maze III procedure,
      which is associated with a higher incidence of postoperative sinus rhythm,
      improved long-term sinus node function, fewer pacemaker requirements, less
      arrhythmia recurrence, and improved long-term atrial transport function. In
      addition, the maze III procedure is technically less demanding than either the
      maze I or maze II procedure. Therefore, the maze III procedure is now the
      technique of choice for the management of medically refractory atrial
      fibrillation.

PMID- 7637366
TI  - Modification of the maze procedure for atrial flutter and atrial fibrillation.
      II. Surgical technique of the maze III procedure.
AB  - The operative technique of the maze III procedure for the treatment of patients
      with medically refractory atrial flutter and atrial fibrillation is described in
      a sequential fashion. The accompanying diagrams of the procedure are illustrated
      from the view of the operating surgeon.

PMID- 7637367
TI  - Regulation of the aortic valve opening. In vivo dynamic measurement of aortic
      valve orifice area.
AB  - Aortic valve orifice area was dynamically measured in anesthetized dogs with a
      new measuring system involving electromagnetic induction. This system permits us
      real-time measurement of the valve orifice area in beating hearts in situ. The
      aortic valve was already open before aortic pressure started to increase without
      detectable antegrade aortic flow. Maximum opening area was achieved while flow
      was still accelerating at a mean of 20 to 35 msec before peak blood flow. Maximum
      opening area was affected by not only aortic blood flow but also aortic pressure,
      which produced aortic root expansion. The aortic valve orifice area's decreasing
      curve (corresponding to valve closure) was composed of two phases: the initial
      decrease and late decrease. The initial decrease in aortic valve orifice area was
      slower (4.1 cm2/sec) than the late decrease (28.5 cm2/sec). Aortic valve orifice
      area was reduced from maximum to 40% of maximum (in a triangular open position)
      during the initial slow closing. These measurements showed that (1) initial slow
      closure of the aortic valve is evoked by leaflet tension which is produced by the
      aortic root expansion (the leaflet tension tended to make the shape of the aortic
      orifice triangular) and (2) late rapid closure is induced by backflow of blood
      into the sinus of Valsalva. Thus, cusp expansion owing to intraaortic pressure
      plays an important role in the opening and closing of the aortic valve and aortic
      blood flow.

PMID- 7637368
TI  - Comparison of the effect of monopolar and bipolar cauterization on skeletonized,
      dissected internal thoracic arteries.
AB  - The internal thoracic artery is preferable to the saphenous vein for use as a
      conduit for coronary artery bypass. More extensive use is possible if this artery
      is mobilized in a skeletonized form to provide greater length. Internal thoracic
      arteries are usually mobilized with cauterization. This study compared the
      effectiveness and effects on neighboring areas of division of the branches of the
      canine internal thoracic artery with bipolar cauterization and monopolar
      cauterization. Branch closure was significantly more secure in the bipolar
      cauterization group, with bleeding in 25 (9%) of 279 branches of 15 internal
      thoracic arteries treated with monopolar cauterization, in contrast to bleeding
      in 4 (1.3%) of 306 branches in the 15 internal thoracic arteries treated with
      bipolar cauterization, which were paired with the group treated with monopolar
      cauterization. The group of internal thoracic arteries treated with monopolar
      cauterization had a significantly higher prevalence of leakage when luminal
      pressure was increased from 120 to 160 mm Hg. Scanning electron microscopy
      demonstrated partial loss of endothelial cells on the flow surface of internal
      thoracic arteries treated with bipolar cauterization, compared with almost
      complete loss of endothelial cells around the orificial areas after monopolar
      cauterization. Secondary bipolar cauterization treatment caused only slightly
      more damage than primary treatment, but secondary monopolar cauterization was
      much more severe and extensive than primary treatment. These data suggest that
      bipolar cauterization is preferable to monopolar cauterization for skeletonized
      dissection of the internal thoracic artery.

PMID- 7637370
TI  - Swallowing dysfunction after cardiac operations. Associated adverse outcomes and
      risk factors including intraoperative transesophageal echocardiography.
AB  - The frequency, importance to patient outcomes, and independent predictors of
      postoperative swallowing dysfunction documented by barium cineradiography were
      examined in 869 patients undergoing cardiac operations over a 12-month period.
      Swallowing dysfunction was diagnosed in 34 patients (4% incidence) and was
      associated with documented pulmonary aspiration in 90% of these patients,
      increased frequency of pneumonia (p < 0.0001), need for tracheostomy (p =
      0.0002), length of stay in the intensive care unit (p = 0.0001), and duration of
      hospitalization after the operation (p = 0.0001). Independent predictors of
      postoperative swallowing dysfunction determined by multivariate logistic
      regression included age (p < 0.001), length of tracheal intubation after the
      operation (p = 0.001), and intraoperative use of transesophageal echocardiography
      (p = 0.003). Dysfunctional swallowing after cardiac operations, a serious
      complication significantly related to postoperative respiratory morbidity and
      extended length of hospitalization, is more common in older patients. An
      association between intraoperative use of transesophageal echocardiography and
      swallowing dysfunction was also observed in our patients.

PMID- 7637369
TI  - Aortic valve replacement with freehand autologous pericardium.
AB  - Fifty-one patients with a mean age of 31.2 years underwent aortic valve
      replacement with glutaraldehyde-treated autologous pericardium. Pure aortic
      regurgitation was present in 28 (54.9%), stenosis in 9, and mixed disease in 14.
      Simultaneous mitral valve repair was done in 17 patients and replacement in 1.
      There were no hospital and two late deaths. Three patients required reoperation
      because of failure of the pericardial valve as a result of infective endocarditis
      in two (5 and 31 months after operation) and commissural tear at 8 months in
      another. One patient underwent reoperation at 24 months because of failure of the
      mitral valve repair. The pericardial aortic valve, which had 2+ regurgitation
      since the first operation, was also replaced. Macroscopic and microscopic
      examination findings in the excised pericardium were excellent. No thromboembolic
      events have been detected and no patient received anticoagulation therapy except
      one after mitral valve reoperation and replacement with a mechanical valve. The
      actuarial survival was 84.53% +/- 12.29% at 60 months, freedom from failure of
      the aortic reconstruction 83.83% +/- 8.59%, and freedom from any event 72.59% +/-
      12.79%. Doppler echocardiographic study at most recent follow-up showed a mean
      gradient of 12.56 +/- 8.10 mm Hg and mean regurgitation on a scale from 0 to 4+
      of 0.80 +/- 0.66. Although the maximum follow-up is only 5 years, the results
      obtained so far encourage us to continue replacing the aortic valve with
      stentless autologous pericardium.

PMID- 7637371
TI  - Improved hypothermic preservation of rat hearts by furosemide.
AB  - The effect of furosemide, a blocker of the Na+/K+/Cl- cotransporter, on
      hypothermic preservation of rat hearts was studied with use of the Langendorff
      perfusion system and electron microscopy. Furosemide significantly improved the
      mechanical recovery and the coronary flow of the hearts preserved for 8 hours in
      St. Thomas' Hospital cardioplegic solution at a temperature of 4 degrees C.
      Furosemide at the concentration of 100 mumol/L was found to have an optimal
      effect, whereas at high concentrations (1000 mumol/L) it was found to have toxic
      effects. In addition, furosemide reduces the time elapsed between the end of the
      preservation time and the resumption of myocardial contractions. Ultrastructural
      evaluations were done in which the presence of swollen mitochondria was chosen as
      a criterion of hypothermic ischemic damage to the myocardium. Morphometric
      analysis indicated that the mitochondrial volume of hearts stored for 8 hours in
      St. Thomas' Hospital cardioplegic solution increased by 72% as compared with the
      mitochondrial volume of hearts that were not exposed to the hypothermic ischemic
      conditions (control group). The addition of 100 mumol/L furosemide to the
      cardioplegic solution resulted in a significant reduction of mitochondrial
      swelling during the period of 8 hours' storage, which amounted only to 28% as
      compared with the figure for the control group. The reduction of mitochondrial
      swelling by furosemide and the improved mechanical and coronary flow recoveries
      are thought to be related to the blocking of the sarcolemmal Na+/K+/Cl-
      cotransporter and consequently the reduction of the Na+ influx during hypothermic
      ischemic storage.

PMID- 7637372
TI  - The impact of implantable cardioverter-defibrillators on mortality among patients
      on the waiting list for heart transplantation.
AB  - Implantable cardioverter-defibrillators were investigated for their impact on
      mortality in 228 consecutive heart transplant candidates on the waiting list for
      transplantation (207 patients without and 21 with implantable cardioverter
      defibrillator therapy). The mortality rate in 207 patients without implantable
      cardioverter-defibrillator therapy was 23.2% and in 21 patients with implantable
      cardioverter-defibrillator therapy was 4.7%. In a Cox proportional hazards model
      for all 228 study patients (mortality while on the waiting list: 21.5%;
      transplantation rate: 54.8%), the absence of an implantable cardioverter
      defibrillator was only a marginally significant predictor of mortality (p =
      0.079). However, the absence of an implantable cardioverter-defibrillator was a
      powerful predictor of mortality for a subgroup of 134 patients with high-grade
      ventricular arrhythmias on Holter electrocardiography (mortality while on the
      waiting list: 26.1%; transplantation rate: 54.5%; p = 0.022) and for a subgroup
      of 58 survivors of sudden cardiac death (mortality while on the waiting list:
      22.4%; transplantation rate: 56.9%; p = 0.018). Implantable cardioverter
      defibrillator therapy can be strongly recommended in transplant candidates with a
      history of sudden cardiac death. Recommendations for an expanded, prophylactic
      use of implantable cardioverter-defibrillator therapy in heart transplant
      candidates cannot be given.

PMID- 7637373
TI  - Deep venous thrombosis and pulmonary embolism after lung transplantation.
AB  - The incidence of deep venous thrombosis or pulmonary embolism after lung or heart
      lung transplantation has not been well defined. Pulmonary embolism may be of
      particular concern in the postoperative period owing to an inadequately developed
      or absent collateral bronchial circulation and potential risk of pulmonary
      infarction. Fourteen (12.1%) of 116 patients undergoing either lung (n = 87) or
      heart-lung (n = 29) transplantation developed thromboembolic complications 10
      days to 36 months after operation. Deep vein thrombosis developed in nine
      patients, including three with upper body thrombosis related to indwelling
      central venous catheters. Seven patients (6%) had pulmonary embolism, and three
      of them died. Resolution of pulmonary embolism was successfully accomplished by
      selective pulmonary artery infusion of urokinase in three patients without
      complications. Our experience indicates that deep vein thrombosis and pulmonary
      embolism are significant problems after lung transplantation. Mortality is high
      in those patients in whom pulmonary embolism develops. Therefore, a comprehensive
      prevention protocol is warranted.

PMID- 7637374
TI  - Hypereosinophilic syndrome: cause of prosthetic valve obstruction.

PMID- 7637375
TI  - A dehydromonocrotaline-induced pulmonary hypertension model in the beagle.

PMID- 7637376
TI  - A technique to minimize air leakage after excision of emphysematous bulla of the
      lungs.

PMID- 7637378
TI  - Extramedullary hematopoiesis presenting as an intraatrial mass in a patient with
      chronic myelogenous leukemia.

PMID- 7637377
TI  - Intrapulmonary benign fibrous tumor of the pleura.

PMID- 7637379
TI  - Primary aortic sarcoma: resection by total arch replacement.

PMID- 7637380
TI  - Endovascular approach for an intracranial mycotic aneurysm associated with
      infective endocarditis.

PMID- 7637381
TI  - Combined coronary artery bypass grafting and excision of adrenal
      pheochromocytoma.

PMID- 7637382
TI  - Repair of tetralogy of Fallot with anomalous origin of left anterior descending
      coronary artery.

PMID- 7637383
TI  - Nebulized synthetic surfactant in reperfusion injury after single lung
      transplantation.

PMID- 7637384
TI  - Morphology of critically stenotic aortic valves.

PMID- 7637385
TI  - Mid-term follow-up after heart valve replacement with CarboMedics bileaflet
      prostheses.

PMID- 7637386
TI  - Tracheal sleeve pneumonectomy for bronchogenic carcinoma.

PMID- 7637387
TI  - Thoracic Surgery Workforce Report. The fourth report of the Thoracic Surgery
      Workforce Committee of The American Association for Thoracic Surgery and The
      Society of Thoracic Surgeons.
AB  - To determine demographics, practice patterns, and work volume of North American
      thoracic surgeons, we sent a detailed survey to all members of The American
      Association for Thoracic Surgery and The Society of Thoracic Surgeons between
      January and May 1993 to determine data for 1992; 3049 of 3487 (87%) thoracic
      surgeons responded and 2677 (88%) were in active practice. Ninety-seven percent
      were male and 3% female, with a mean age of 52 years. Sixty-five percent
      considered fee-for-service as their primary compensation mode. Only 24% do
      isolated subspecialty work: 2% pediatric cardiac surgery. 10% general thoracic
      surgery, and 12% adult cardiac surgery. Seventy-six percent of respondents do
      both cardiac and thoracic operations. Workload data for adult cardiac, pediatric
      cardiac, general thoracic, peripheral vascular, and pacemaker operations were
      requested. Volume data were cross-correlated with age, 10 geographic regions
      including Canada, type of practice, and type of compensation and were cross
      checked by hospital discharge data for 1992. These data were compared with data
      from similar surveys performed in 1976, 1980, and 1985, under the auspices of the
      same two societies; these latter surveys used diplomates of the American Board of
      Thoracic Surgery as their database. Workloads have increased over previous
      surveys. Most surgeons do a wide variety of thoracic operations, and exclusive
      designations are in the minority.

PMID- 7637388
TI  - Multidrug resistance is more than MDR1 activity.

PMID- 7637389
TI  - Increased ratio between deoxycytidine kinase and thymidine kinase 2 in CLL
      lymphocytes compared to normal lymphocytes.
AB  - Deoxycytidine kinase (dCK) is important in the 5'-phosphorylation of
      deoxynucleoside analogs. Like dCK, thymidine kinase 2 (TK2) catalyzes the initial
      step of the phosphorylation of dcyd to dCTP. Thymidine is a strong inhibitor of
      the dCK activity of TK2. We examined the ratio of the dcyd phosphorylation
      carried out by dCK and by TK2 (dCK/TK2-dcyd) in lymphocytes from CLL patients and
      from donors. In the CLL lymphocytes we found a 3.5-fold average increase.
      Therefore, we conclude that addition of thymidine in the treatment of CLL with
      deoxynucleoside analogs will not be of any advantage. Furthermore, our results
      can explain earlier findings in CML and AML lymphocytes where the ara-C
      phosphorylation was twice the dcyd phosphorylation.

PMID- 7637390
TI  - The induction kinetics of Il-8 messenger RNA in HL60 cells demonstrate the
      participation of negative-acting gene(s).
AB  - Interleukin-8 (IL-8) mRNA was rapidly, but not permanently, induced at high
      levels by phorbol-12myristate-13acetate (PMA) in HL60 cells. Ongoing protein
      synthase does not seem to be required for the initial induction of IL-8 gene
      expression. However, the rate of transient induction kinetics was modulated by
      cycloheximide (CHX) indicating that secondary response genes are involved in the
      regulation of IL-8 RNA levels. Repression of the induced IL8 mRNA by 21 h PMA
      treatment was due to reduced transcriptional activity of the gene. In HL60 cells
      stimulated for 1.5 and 21 h the half-lives of the lL-8 transcripts were markedly
      increased, suggesting the presence of negatively-acting transcriptional
      regulator(s).

PMID- 7637391
TI  - The protein kinase C inhibitor H7 blocks phosphorylation of stathmin during TPA
      induced growth inhibition of human pre-B leukemia REH6 cells.
AB  - The human pre-B acute lymphoblastic leukemia cell line REH6 was used to analyze
      the regulation of a ubiquitous intracellular phosphoprotein stathmin (Mr 19,000,
      pl = 5.6-6.2). We demonstrated by 32P-labeling that the short (1 h) treatment of
      the REH6 cells with the tumor promoting phorbol ester, 12-O-tetradecanoylphorbol
      13-acetate (TPA), resulted in a rapid phosphorylation of at least three (P1, P2
      and P3) stathmin isoforms without an alteration of stathmin isoform expression.
      Furthermore, Western blot analysis with specific antiserum showed that the
      prolonged period (48 h) of TPA treatment partially reduced protein levels
      particularly of two (N2 and P2) stathmin isoforms. The potent and relatively
      specific protein kinase C (PKC) inhibitor, 1,(5
      isoquinolinesulphonyl)2methylpiperasine dihydrochloride (H7), partially inhibited
      these TPA effects, whereas the specific calmodulin inhibitor R24571
      (calmidazolium) had no effect upon these events. Our findings suggest that
      stathmin phosphorylation in REH6 cells could be in part mediated by PKC
      activation.

PMID- 7637392
TI  - Enhanced oxygen consumption and fatty acid metabolism in rat bone marrow with
      acute promyelocytic leukaemia.
AB  - The metabolism of bone marrow cells during the development of acute promyelocytic
      leukaemia has only been scarcely characterized, even though such knowledge might
      improve our understanding of the mechanisms of leukemogenesis as well as of drug
      treatment failure. We have investigated the in vitro oxygen consumption and the
      metabolism of palmitate in rat bone marrow cells during development of acute
      promyelocytic leukaemia. As the leukaemia progressed, the cellular oxygen
      consumption, the beta-oxidation of palmitate and the incorporation of palmitate
      into phospholipids all increased markedly. Cyclophosphamide supplement led to a
      temporary reduction of the palmitate metabolism, but did not lower the increased
      oxygen consumption. We conclude that the cellular metabolic rate is elevated
      during the progression of acute promyelocytic leukaemia, and that this might
      reflect an enhanced proliferative rate of the malignant cells.

PMID- 7637393
TI  - AML blasts variably express interleukin 2 receptor alpha, beta or gamma chains
      without measurable effects on proliferation, cytokine message expression or
      surface expression of adhesion molecules upon stimulation with interleukin 2.
AB  - Preliminary clinical studies including interleukin 2 (IL-2) in chemotherapy
      strategies for treatment of acute myeloblastic leukemia (AML) suggest that IL-2
      may improve the disease-free survival of the patients. Because of reports showing
      interleukin 2 receptor expression on AML blasts, it is important to know whether
      IL-2 may directly influence these leukemic cells. In initial studies using flow
      cytometry to analyze surface expression of interleukin 2 receptors (IL-2R), we
      found expression of the IL-2R alpha chain on blast cells in 26% and of the IL-2R
      beta-chain in 81% of the patients. To confirm these results at the
      transcriptional level, we studied the expression of RNA of the IL-2R alpha, beta,
      and gamma chains by RT-PCR in the bone marrow of 38 newly diagnosed patients with
      AML and in three AML-derived cell lines. RNA of the alpha chain was detectable in
      11/38 patients, the beta chain in 10/38 patients and the gamma chain in 30/38
      patients with AML. Blast cells obtained from colonies growing in semisolid media
      expressed mRNA for IL-2R. RNA for all three IL-2R chains was expressed in lines
      KG1, HEL 92.1.7 and K562. In comparison with unstimulated cell lines, incubation
      of the three lines with various amounts of IL-2 over 3 and 14 days did not
      increase their growth or change message expression of IL-2R, IL-10, and TGF-beta
      and surface expression of the adhesion molecules CD 11, CD 18, CD 29 and CD 54.
      In conclusion, despite expression of IL-2 receptors, AML blasts do not respond to
      IL-2 by proliferation, message expression for various cytokine genes and surface
      expression of cellular adhesion molecules.

PMID- 7637394
TI  - Successful treatment of an infant with veno-occlusive disease developed after
      allogeneic bone marrow transplantation by tissue plasminogen activator, heparin
      and prostaglandin E1.
AB  - A 15-month-old boy with severe aplastic anemia developed veno-occlusive disease
      (VOD) after allogeneic bone marrow transplantation (BMT), in which the
      preparative regimen included 50 mg/kg/day cyclophosphamide and anti-lymphocyte
      globulin for 4 consecutive days. The diagnosis was made based on clinical
      symptoms and data including, hepatomegaly, right upper quadrant abdominal pain,
      jaundice, ascites, coagulopathy and thrombocytopenia which was refractory to
      transfusions of platelet concentrate. We gave 2, 3, 5 and 5 mg/day/body of
      recombinant tissue plasminogen activator (tPA) followed by heparin and
      prostaglandin E1 (PGE1) effectively and without significant side effect on days
      9, 10, 13 and 14, respectively. Clinical and biochemical improvement was steady
      and dramatic. We suggest that tPA following continuous heparin and PGE1 infusion
      may be useful in the treatment of VOD even in infantile cases.

PMID- 7637395
TI  - Characterization of 7q--by FISH technique of a case with acute myelogenous
      leukemia evolving from agnogenic myeloid metaplasia.
AB  - We present a new case of acute myelogenous leukemia (AML) which evolved from
      agnogenic myeloid metaplasia (AMM). Routine cytogenetic techniques revealed a
      terminal deletion of one chromosome 7 (del (7) (q21)). When metaphases were
      hybridized with the 7q specific telomeric probe, a signal was detected at the
      distal q arm of the deleted chromosome 7 suggesting an interstitial deletion and
      the cytogenetic diagnosis was changed to 46,XY, del(7) (q21.1q36.2). Apparently,
      precise characterization of such deletions may have gone undetected, owing to the
      lack of technology, and deletions that have been previously regarded as terminal
      may very well be interstitial. Undoubtedly, precise identification of genetic
      abnormalities may lead to a better classification which may help to assign
      patients into sub-subgroups within the specific chromosomal abnormalities to
      initiate better therapeutic modalities and decisions.

PMID- 7637396
TI  - Hairy cell leukemia--an unusual presentation.
AB  - Hairy cell leukemia is a chronic lymphoproliferative disorder affecting middle
      aged adults, with the median age of 50-55 years. The majority of the patients
      present with cytopenia. A high count is usually a feature of the hairy cell
      leukemia variant. We report a case of a 23-year-old male who presented with fever
      and cough of 15 days duration. His peripheral blood count was 63 x 10(9)/l. His
      peripheral blood and bone marrow smear showed hairy cells which were positive for
      tartarate-resistant acid phosphatase stain. Surface markers and electron
      microscopic study on peripheral blood ruled out hairy cell leukemia variant as a
      differential diagnosis.

PMID- 7637397
TI  - High-dose 6-mercaptopurine infusions and tumor lysis syndrome.

PMID- 7637398
TI  - MSNA press conference on the safety and quality of patient care in Maine.

PMID- 7637399
TI  - How a latex allergy has affected my life.

PMID- 7637400
TI  - Tort reform and malpractice liability insurance.
AB  - Legal factors related to the malpractice liability insurance purchased by general
      dentists in the United States were investigated using a comprehensive
      multivariate model that assessed the contribution of legal provisions affecting
      the probability of a malpractice claim, the probability of a payment, and the
      average size of the payment. General practice dentists in the United States were
      selected randomly, and 3,048 dentists were studied by mail survey. A number of
      legal statutes (periodic payment allowed, percentage fault liability informed
      consent limits, limits on res ipsa loquitor, attorney fee control, some statute
      of limitations provisions) had the intended effect of reducing the malpractice
      insurance sought by dentists. Other provisions, such as binding arbitration, may
      have unintended cost-raising effects. Previous malpractice claims were associated
      with purchasing greater amounts of insurance. These findings have implications
      for future changes in the legal system as part of health care reform.

PMID- 7637401
TI  - A chronic disease score with empirically derived weights.
AB  - Different types of medication prescribed during a 6-month period for the
      treatment and management of chronic conditions were utilized in the refinement
      and validation of a chronic disease score. Prescription data, in addition to age
      and sex, were utilized to develop a chronic disease score based on empirically
      derived weights for each of three outcomes: total cost, outpatient cost, and
      primary care visits. The ability of the revised chronic disease score to predict
      health care utilization, costs, hospitalization, and mortality was compared to an
      earlier version of the chronic disease score (original) that was derived through
      clinical judgments of disease severity. The predictive validity of the chronic
      disease score is also compared to ambulatory care groups, which utilize
      outpatient diagnoses to form mutually exclusive diagnostic categories. Models
      based on a concurrent 6-month period and a 6-month prospective period (ie, the 6
      month period after the chronic disease score or ambulatory care group derivation
      period) were estimated using a random one half sample of 250,000 managed-care
      enrollees aged 18 and older. The remaining one half of the enrollee population
      was used as a validation sample. The revised chronic disease score showed
      improved estimation and prediction over the original chronic disease score. The
      difference in variance explained prospectively by the revised chronic disease
      score versus the ambulatory care groups, conversely, was small. The revised
      chronic disease score was a better predictor of mortality than the ambulatory
      care groups. The combination of revised chronic disease score and ambulatory care
      groups showed only marginally greater predictive power than either one alone.
      These results suggest that the revised chronic disease score and ambulatory care
      groups with empirically derived weights provide improved prediction of health
      care utilization and costs, as well as hospitalization and mortality, over age
      and sex alone. We recommend the revised chronic disease score with total cost
      weights for general use as a severity measure because of its relative advantage
      in predicting mortality compared to the outpatient cost and primary care visit
      weights.

PMID- 7637402
TI  - Convergence or divergence of male and female physicians' hours of work and
      income.
AB  - This article verifies if the increase in the percentage of women in the medical
      profession led to the convergence of male and female physicians' hours of work as
      well as income. Active physicians in Quebec in 1978 were compared to the ones in
      1988. Data were obtained from the computerized files of the Quebec Corporation of
      Physicians and the Regie d'assurance-maladie du Quebec. Despite the increasing
      representation of women in the medical profession, gender differences in hours
      worked and income remained. However, results also showed a tendency toward a
      convergence in total hours of work, more behavioral variation among women
      physicians and some behavioral change among men. The experience of the past
      should thus not be used as the basis for projections of future physician
      productivity or for medical manpower planning purposes without a careful analysis
      of trends in behavioral changes.

PMID- 7637403
TI  - Diagnosis-related group refinement with diagnosis- and procedure-specific
      comorbidities and complications.
AB  - Diagnosis-related groups have been revised through more refined uses of secondary
      diagnoses. Under the refined diagnosis-related groups, patients are distinguished
      with respect to classes of secondary diagnoses that are disease- and procedure
      specific. Each class represents a different level of utilization for a given
      principal diagnosis or surgical procedure. The refined system was evaluated with
      national data from the Medicare program. Estimates of hospital costs and
      utilization based on refined diagnosis-related groups were more precise than
      those based on unrefined diagnosis-related groups. This approach to diagnosis
      related group refinement does not represent a radical departure from the current
      diagnosis-related group framework and does not require new data collection
      efforts. Moreover, a payment system based on the refined model is less affected
      by the ordering of the diagnoses than under the existing diagnosis-related group
      system. How the refined diagnosis-related group framework can accommodate future
      refinements at all levels of the classification scheme is also discussed.

PMID- 7637404
TI  - Medicare payments from diagnosis to death for elderly cancer patients by stage at
      diagnosis.
AB  - Although extensive resources go to cancer care, national population-based data on
      the costs of such care at the patient level have been unavailable. Medicare
      payments subsequent to diagnosis of cancer for elderly enrollees with five common
      cancers were estimated using tumor registry data from the Surveillance,
      Epidemiology, and End Results Program linked to Medicare claims from 1984 to
      1990. The time between diagnosis and death was divided into four phases
      corresponding to the clinical course of solid tumors, average payments for each
      phase were estimated (including payments for services not related to cancer),
      then phase-specific payment data were aggregated. Average payments by phase
      varied among cancer sites, especially in the initial care phase, where payments
      were highest for lung and colorectal cancers ($17,500 in 1990 dollars) and lowest
      for female breast cancer ($8,913). Total Medicare payments from diagnosis to
      death were highest for persons with bladder cancer ($57,629) and lowest for those
      with lung cancer ($29,184). Low payments for persons with lung cancer
      corresponded to brief survival times. Persons diagnosed at earlier stages
      incurred higher total payments between diagnosis and death than those diagnosed
      at later stages, reflecting their longer survival. This implies that early
      detection may increase total Medicare expenditures by extending beneficiaries'
      lives. However, Medicare payments per year of survival were lower for earlier
      stages. Data on Medicare payments subsequent to diagnosis of cancer are useful
      for identifying the cost implications of differences in treatment patterns by
      demographic characteristics, geography, and delivery systems; comparing the
      financial impact of alternative therapies; evaluating the long-term cost impacts
      of screening and prevention programs; and risk-adjusting payments to health
      plans.

PMID- 7637406
TI  - The analysis of censored treatment cost data in economic evaluation.
AB  - This article investigates the way in which the presence of censored cost data in
      clinical trials should dictate the inferential tests adopted when comparing
      treatment and nontreatment groups for the purpose of economic evaluation. The
      authors argue that the techniques of survival analysis are appropriate where
      censoring is present, and that bias will be imparted if cruder methods are used
      to analyze cost data, even if that data is drawn from a relevant population. The
      first section of the article discusses the problem of censoring and survival
      analysis, while the second examines three methods of dealing with censored cost
      data and possible biases resulting from them. The third section presents results
      from actual trial data using the three methods described in the preceding
      section. Conclusions are presented in section four, where it is argued that these
      methodological issues are likely to become more important as economists are
      called upon to evaluate the treatment of chronic conditions using data from
      clinical trials with finite end points.

PMID- 7637405
TI  - Factors associated with choosing a chiropractor for episodes of back pain care.
AB  - Back pain is a common illness and chiropractors provide a large proportion of
      back pain care in the United States. This is the first study to systematically
      compare chiropractic patients with those who saw other providers for back pain.
      The authors analyzed data from the RAND Health Insurance Experiment, a community
      based study of the use of health services. Insurance claims forms were examined
      for all visits specified by the patient as occurring for back pain. Visits were
      grouped into episodes using decision rules and clinical judgment. The primary
      provider of back pain care was defined as the provider who delivered most of the
      services. Sociodemographic and health status and attitudes variables of patients
      were examined for association with the choice of chiropractor. Multivariate
      logistic regression models were constructed to calculate adjusted odds ratios for
      independent predictors. There were 1020 episodes of back pain care made by 686
      different persons and encompassing 8825 visits. Results indicated that
      chiropractors were the primary provider for 40% of episodes, and retained as
      primary provider a greater percentage of their patients (92%) who had a second
      episode of back pain care than did medical doctors. Health insurance experiment
      site, white race, male sex, and high school education were independent predictors
      of choosing a chiropractor. Conclusions suggested that chiropractors were the
      choice of one third of all patients who sought back pain care, and provided care
      for 40% of all episodes of care. Geographic site, education, gender, and income
      were independent patient factors predicting chiropractic use.

PMID- 7637407
TI  - Sequential events contributing to variations in cardiac revascularization rates.
AB  - Numerous studies have demonstrated the importance of race, payor, and gender in
      determining the use of cardiac services, including revascularization procedures
      (bypass surgery and angioplasty). However, there has been less investigation into
      where and when in the process of care differences in utilization arise. In this
      report, the authors examined the sequence of events leading to the use of
      revascularization procedures, identifying four phases of care (prehospital,
      intrahospital, interhospital, and posthospital). Following a cohort of 5857
      patients admitted to California hospitals with acute myocardial infarction in
      1991, the authors found differences in treatment probabilities during nearly
      every phase for different racial and payor groups. For example, compared with
      patients who are uninsured, patients with private insurance were more likely to
      be admitted initially to a hospital offering revascularization (adjusted odds
      ratio [OR] = 1.40, 95% confidence interval [CI] 1.30 to 1.51). Moreover, once
      admitted to such a hospital, private patients were more likely to undergo
      revascularization (adjusted OR = 2.30; 95% CI 1.80 to 2.94). They were also more
      likely to undergo transfer to receive revascularization (adjusted OR = 1.22; 95%
      CI 1.03 to 1.45), and to be readmitted for revascularization (adjusted OR = 1.60;
      95% CI 1.13 to 2.27). Previously reported discrepancies in service use represent
      the cumulative effects of multiple phases during which different racial and payor
      groups experience different processes of care.

PMID- 7637408
TI  - [Allogenic bone marrow transplantation in multiple myeloma. Analysis of 12
      consecutive cases].
AB  - BACKGROUND: Allogeneic bone marrow transplantation (BMT) is the only potentially
      curative treatment in multiple myeloma (MM). METHODS: From january 1986 to
      december 1993, 12 cases (10 males and 2 females) underwent BMT in the authors'
      institution. The mean age of the series was 39 years (range 23-49). The situation
      of the myeloma on initiation of the conditioning was: complete remission (CR) in
      2 cases, objective response in 5 cases, partial response in 1 case and treatment
      resistance in 4 cases. The conditioning schedule included cyclophosphamide (120
      mg/kg) and total body irradiation (10-14 Gy) with or without melfalan at high
      doses in 11 patients and busulfan (16 mg/kg) and cyclophosphamide (120 mg/kg) in
      1 case. The prophylaxis of graft versus host disease (GVHD) was carried out with
      methotrexate and cyclosporine A (CsA) in 7 cases, CsA plus prednisone in 2 cases
      and 3 patients received CsA plus bone marrow partially depleted of T lymphocytes
      by elutriation. RESULTS: The situation of the myeloma with regard to response
      following transplantation was: unevaluable in 1 case, resistant in 1 case,
      objective response in 2 cases and CR in 8 cases. Seven out of the 10 patients at
      risk presented grades II-IV GVHD. Four of the 8 patients who were in CR following
      transplantation died due to post transplant complications and 2 out of the 6
      relapsed 9 months after the transplant while 2 remain in CR at 5 and 8 years
      after the transplant, respectively. Nine patients died due to infection in 2
      cases, GVHD and infection in 4 cases, GVHD and hemorrhage in 1 case and
      progression and infection in 2 cases. Of the 3 surviving patients, 1 relapsed at
      14 months after the transplant and two remain in CR at 5 and 8 years post
      transplantation. CONCLUSIONS: Bone marrow transplantation conditioning gives
      place to a high number of complete remission in multiple myeloma. However, the
      incidence of acute grade II-IV graft versus host disease and mortality due to
      complications related to the transplantation are very high. Nonetheless, a
      proportion of patients may achieve curation with bone marrow transplantation.

PMID- 7637410
TI  - [Video-assisted thoracic surgery].

PMID- 7637409
TI  - [Hyperdynamic circulatory syndrome of chronic liver disease: physiopathology of a
      multiorganic entity].

PMID- 7637411
TI  - [Espartosis. A new type of extrinsic allergic alveolitis among construction
      plasterers].
AB  - The clinical characteristics of three plasterers in contact with esparto and who
      presented a picture of extrinsic allergic alveolitis which was peculiar because
      of their being hyperacute and causing hypoxemia. In addition to a review of 5
      previously published sporadic cases the clinical picture of this new type of
      apparently infrequent alveolitis is described. The causal antigen is unknown
      although contamination by fungus or the addition of raw esparto may be the origin
      of the disease. After a review of the literature regarding this subject, the
      authors suggest that, in addition to cases of asthma and chronic airway
      obstruction, the patients with extrinsic allergic alveolitis be included under
      the name of espartosis following esparto dust inhalation.

PMID- 7637412
TI  - [Empathy: the quintessence of the art of medicine].

PMID- 7637413
TI  - [Glycoproteins, glycosaminoglycans, and urolithiasis].

PMID- 7637414
TI  - [Leukocytoclastic vasculitis and factor XIII deficiency].

PMID- 7637415
TI  - [Acute abdomen as presentation form of Lemierre's syndrome].

PMID- 7637416
TI  - [Pubic osteomyelitis].

PMID- 7637417
TI  - [Mortality from chronic liver disease in patients with HIV infection].

PMID- 7637418
TI  - [Seroprevalence of brucellosis in La Cerdanya].

PMID- 7637419
TI  - [C-erbB-2 protein in ovarian epithelial cancer: correlation between expression in
      tumor tissue and blood levels].
AB  - BACKGROUND: Among 20 to 30% of the patients with ovarian cancer present
      overexpression of the c-erbB protein in the tumor tissue although its clinical
      significance has not been clearly established. In patients with a disseminated
      neoplasm and overexpression of c-erbB an increase in the extracellular portion of
      this protein may be detected in serum. The aim of this study was to determine the
      c-erbB protein in serum and in tumoral tissue in patients diagnosed with ovarian
      epithelial carcinoma. METHODS: The serum concentration of the c-erbB protein was
      quantified by ELISA techniques in 60 blood donor women (control group) and in 99
      patients with ovarian cancer. Likewise, the expression of the c-erbB protein was
      determined in tumoral tissue by immunohistochemical techniques in the 99 patients
      with ovarian cancer. The correlation between overexpression and elevated serum
      values was analyzed. RESULTS: The mean c-erbB values obtained in the serum of the
      control group was 10.9 U/ml (SD: 2.8) with a range of 1.5-17.0. Serum
      determination was carried out in absence of the tumor in 49 patients being
      positive in 2 cases. In 7 patients the determination was performed in the
      presence of peritoneal implants of a diameter of less than 2 cm with none being
      positive. Serum determination was carried out in 43 patients in the presence of
      implants greater than 2 cm and 14 (32.5%) were positive. A further 153
      determinations were performed during follow up of the 99 patients, 62 in tumor
      absence (3.2% positive), 2 in the presence of a tumor of less than 2 cm (none
      positive) and 89 in the presence of a tumor greater than 2 cm (34.8% positive). A
      correlation was found between elevated c-erbB serum values in the presence of a
      disseminated tumors and overexpression of tumoral tissue (p: 0.0011).
      CONCLUSIONS: A third of the patients with ovarian cancer and peritoneal implants
      of a diameter greater than 2 cm present elevated serum levels of the c-erbB.2
      protein. A correlation was found between serum c-erbB positivity and
      overexpression of the protein in tumoral tissue.

PMID- 7637420
TI  - [Use and presentation of statistics methods in original articles published in
      MEDICINA CLINICA in 1993].
AB  - BACKGROUND: In the last few years a marked increase has been observed in the use
      of statistical techniques in biomedical publications. Some characteristics of the
      statistical quality of the first 100 articles consecutively published in 1993 in
      the section of originals and surveys of the journal MEDICINA CLINICA are
      presented in this study. METHODS: In each original one reviewer identified errors
      and/or criticisms in statistical methodology. An adaptation of the protocol of
      statistical revision made by the journal The Lancet since november 1990 was used
      in addition to its own classification. Likewise, an error and/or criticism
      involving minimum statistical quality necessary was considered as major and that
      which only had a decrease in optimum statistical level was considered as minor.
      Statistical analysis consisted in descriptive tables of the number of originals
      in which each of the classified errors and/or criticisms were observed. RESULTS:
      Sixty-seven percent of the originals (CI 95%: 64;70) presented major errors
      and/or criticisms in design, analysis and inference. The most frequent were found
      in power and sample size (design), need for better analysis (analysis) and lack
      of confidence intervals (inference). Only 15% (CI 95%: 13;17) had major errors in
      statistical presentation and 82% (CI 95%: 80;84) minor errors among which the so
      called orphaned p was of note. CONCLUSIONS: The need for accompanying the p
      values by the confidence intervals or taking the calculation of the required
      sample size into account are of note. Furthermore, the diffusion of explicit
      recommendations concerning the carrying out and presentation of statistical
      analysis is necessary.

PMID- 7637421
TI  - [Continue with rationalization! Increased power of the county councils is a dead
      end].

PMID- 7637422
TI  - [Time for the surgeon to leave the emergency departments?].

PMID- 7637423
TI  - [Hard disc drive problems].

PMID- 7637424
TI  - [Malpractice in health care--the USA is a model for lawyers only].

PMID- 7637426
TI  - [Weight fluctuation--an overestimated risk?].

PMID- 7637425
TI  - [Smoking is not mentioned in connection with deep venous thrombosis].

PMID- 7637427
TI  - [A care program for dementia. Increased cooperation between health care and
      social service].

PMID- 7637428
TI  - [Obese persons have low quality of life. Chubby and good is often thick and
      sick].

PMID- 7637429
TI  - [Ultrasound during pregnancy. Attitudes of the majority of women is positive but
      information is insufficient].

PMID- 7637430
TI  - [Being sick is better than being dead! Medicine in Scandinavia during the Viking
      Age and the early Middle Ages].

PMID- 7637431
TI  - [Platon--the first psychiatrist].

PMID- 7637432
TI  - [Good geographical anamnesis in myiasis. Delayed diagnosis and treatment in
      suspected mosquito bite].

PMID- 7637433
TI  - [Growth-retarded fetuses--a risk group for development of CP. Does careful labor
      reduce the damage?].

PMID- 7637434
TI  - [High standard of Swedish obstetrics, but... Increased centralization improves
      the safety].

PMID- 7637435
TI  - [Natural or technology-based obstetric care? Nature will decide--but with a
      safety net...].

PMID- 7637436
TI  - [Every fifth Swede buys natural drugs and health foods].

PMID- 7637437
TI  - [Documentation behind recommendations is missing].

PMID- 7637438
TI  - [Can health care be financed by patients' fees only?].

PMID- 7637439
TI  - [Social perspective on health care leads to radically new ideas].

PMID- 7637440
TI  - [Wrong to use 2 different methods that do not detect the same patients].

PMID- 7637441
TI  - [Vaccination with the naked DNA. Revolutionary news against infectious diseases].

PMID- 7637442
TI  - [The first part of the goal of a project on xenotransplantation is achieved:
      porcine kidney in human circulation].

PMID- 7637443
TI  - [Treatment of acute myocardial infarction in scarsely populated areas in
      Norrland. Thrombolysis at cottage hospitals saves a lot of time].

PMID- 7637444
TI  - [Low cancer risk among female agricultural workers].
AB  - In a cohort study of cancer incidence, 50,682 women registered in the 1970
      Swedish census as engaged in agriculture were followed up in the national Cancer-
      Environment Register from 1971 to 1987. Instead of the expected incidence of
      5,273 cases, a total of only 4,474 cases were found, yielding a significantly
      reduced standardised incidence ratio (SIR) of 0.85. Thus, site specific SIRs were
      also significantly reduced for cancer of the breast (0.83), cervix uteri (0.40),
      lung (0.46), urinary tract (0.57), and several other sites.

PMID- 7637445
TI  - [Should we perform surgery in asymptomatic carotid stenosis? Good results but let
      us wait for further studies].

PMID- 7637446
TI  - [Insulin-like growth factors. Future treatment in catabolism?].
AB  - Growth is the result of complex interactions between nutrition, stimulating and
      inhibiting signal substances, and target cell response to these substances. The
      insulin-like growth factors, IGF-I and IGF-II, are important growth factors
      throughout life, and function both as endocrine and paracrine hormones. Their
      anabolic and growth promoting actions are mediated via the IGF-I receptor,
      present in all cells apart from liver and adipose cells, which contains the
      homologous insulin receptor. IGF-I expression is regulated both by nutrition and
      by other hormones such as insulin and growth hormone (GH), though GH regulation
      of IGF-I first starts after birth when growth becomes GH- dependent. Treatment
      with recombinant IGF-I has been shown to normalise growth in children with GH
      receptor deficiency. IGF peptides in serum and other fluids are always associated
      with binding proteins (IGFBPs). A family of six polypeptides have been
      characterised. The various IGFBPs have been suggested to function as storage or
      transport proteins, or modulators of IGF action on target cells. Proteases which
      cleave IGFBPs are assumed to increase the bioavailability of IGFs. Most of the
      IGFs in serum are bound to the GH-dependent IGFBP-3 in ternary complexes which
      cannot leave the circulation. The serum IGF-I concentration manifests an age
      dependent pattern, mainly owing to the age-dependent level of GH production.
      After increasing during puberty, IGF-I levels then decrease with increasing
      age.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7637447
TI  - ["The intervention spiral" is forced by screening for cancer].

PMID- 7637448
TI  - [An open information about the American physicians? Critics want a secret
      criminal records registry].

PMID- 7637449
TI  - [Care of abusing physicians in the United States. Voluntariness--for the sake of
      the physician. Commitment--for protection of the patient].

PMID- 7637450
TI  - [Acute respiratory tract infections: recommendations from the Medical Products
      Agency is a document with many questions].

PMID- 7637451
TI  - [A questionable document on treatment of acute respiratory tract infections].

PMID- 7637452
TI  - "The diagnosis should be as reliable here as in the major hospitals." When will
      the "magnetic camera" come to Kungals hospital?.

PMID- 7637453
TI  - [Follow the proposal of the Priority Investigation: do not inform all pregnant
      women about the prenatal diagnosis].

PMID- 7637454
TI  - [HIV and tuberculosis at Venhalsan in Stockholm].

PMID- 7637455
TI  - [Rehabilitation and/or temporary disability pension].

PMID- 7637456
TI  - [Is diabetic retinopathy always a contraindication to thrombolysis?].

PMID- 7637457
TI  - [Disadvantages of breast feeding].

PMID- 7637458
TI  - [Insufficient quality of colorectal cancer surgery!].

PMID- 7637459
TI  - [Should check-ups for 4-year old children be abolished?].

PMID- 7637460
TI  - [Is the expansion of primary health care a contributory cause of our health care
      crisis?].

PMID- 7637461
TI  - [Mutual responsibility in malpractice reporting is important].

PMID- 7637462
TI  - [Increased clinical use of growth factors].

PMID- 7637463
TI  - [Sunscreening agents do not cause cancer but over-reliance on protection is
      hazardous].

PMID- 7637464
TI  - [Filovirus--a cause of hemorrhagic fever].

PMID- 7637465
TI  - [What will be the next plague? Unknown hazards and new types of viruses may
      suddenly emerge].

PMID- 7637466
TI  - [Cytokines. Transmittor substances of the immune system].
AB  - Cytokines are hormone-like proteins and peptides whose principal function is that
      of signalling substances within the immunoinflammatory and haematopoietic
      systems. Since the first cytokines were characterised 15 years ago, over 50
      cytokines have been strictly defined and characterised. Cytokines are classified
      mainly on the basis of functional criteria into families--e.g, interleukins,
      interferons, colony stimulating factors, and chemokines. The article provides a
      broad review of cytokine physiology and pathophysiology with an emphasis on
      recent findings of their involvement in various diseases such as infections,
      autoimmune and haematological disorders, and cancer. Different treatment
      modalities that affect cytokine activity are discussed.

PMID- 7637467
TI  - [Alcohol, provocation, intimidation, increase risk of violence].

PMID- 7637468
TI  - [Impared potency or increased libido? Sex life and drugs].

PMID- 7637469
TI  - [Increased morbidity among the unemployed].

PMID- 7637470
TI  - [From rune stones to genes. The cause of Sjogren-Larsson syndrome is encircled].

PMID- 7637471
TI  - [Blood transfusion is effective in emphysema].

PMID- 7637473
TI  - Can we prevent azole resistance in fungi?

PMID- 7637474
TI  - Adult leukaemia in 1995: new directions.

PMID- 7637472
TI  - Kicking the teenage habit.

PMID- 7637475
TI  - Naltrexone in alcohol dependence.

PMID- 7637476
TI  - In SUPPORT (Study to Understand Prognoses and Preferences for Outcomes and Risks
      of Treatment) of experience and judgment.

PMID- 7637477
TI  - Transluminal aortic aneurysm replacement.

PMID- 7637478
TI  - Thromboprophylaxis with low-molecular-weight heparin in outpatients with plaster
      cast immobilisation of the leg.
AB  - Deep-vein thrombosis is common after plaster-cast immobilisation for traumatic
      injury. We did a randomised prospective study of the effect of low-molecular
      weight heparin on the incidence of deep-vein thrombosis in patients with minor
      injuries treated with plaster-cast immobilisation of the leg. A control group (n
      = 163) received no prophylaxis, the prophylaxis group received low-molecular
      weight heparin once daily (n = 176). The incidence of deep-vein thrombosis in the
      prophylaxis group was 0% (one tailed p < 0.006) vs 4.3% in the control group. No
      severe side-effects of low-molecular-weight heparin were observed.
      Thromboprophylaxis with low-molecular-weight heparin once daily is effective in
      reducing the risk of deep-vein thrombosis in outpatients with plaster-cast
      immobilisation of the leg.

PMID- 7637480
TI  - Vascular function in the forearm of hypercholesterolaemic patients off and on
      lipid-lowering medication.
AB  - To study whether vascular dysfunction in hypercholesterolaemia is reversible, we
      investigated patients without overt arterial disease who were taking maintenance
      treatment for hypercholesterolaemia. Medication was stopped for 2 weeks,
      reinstituted for 12 weeks, and again stopped for 6 weeks. During both maintenance
      treatment and the 12 weeks of step-up medication the lipid profile was improved
      but did not return to normal. Dose-response curves for serotonin-induced
      vasodilatation, an index of nitric oxide-dependent vasodilatation, showed a
      comparable and significant rightward shift after a medication-free period of 2
      and 6 weeks compared with control subjects, indicating endothelial dysfunction,
      which was already maximum after 2 weeks. After 12 weeks of lipid-lowering
      medication, the difference in endothelial function between controls and patients
      had disappeared. Co-infusion of L-arginine, the substrate for nitric oxide
      synthase, returned the impaired serotonin response during hypercholesterolaemia
      to normal, but had no effect on this response in controls or in patients while on
      lipid-lowering medication. Neither endothelium-independent vasorelaxation,
      assessed by sodium nitroprusside infusion, nor vasoconstriction induced by the
      nitric oxide blocker L-NMMA, were different between controls and patients,
      whether the latter were on or off lipid-lowering medication. Our results show an
      L-arginine-sensitive, impaired nitric-oxide-mediated vascular relaxation of
      forearm resistance vessels in hypercholesterolaemia which is reproducible, and
      reversible after short-term lipid-lowering therapy. Demonstration of such changes
      in this readily accessible vascular bed will allow larger trials assessing
      vascular function during lipid-lowering therapy to be done.

PMID- 7637481
TI  - Crimean Congo-haemorrhagic fever treated with oral ribavirin.
AB  - Crimean-Congo Haemorrhagic Fever (CCHF) is an often-lethal haemorrhagic fever
      caused by a tick-borne virus. There are no published data on ribavirin treatment
      of CCHF-infected patients, despite established in-vitro and in-vivo sensitivity.
      We report three health workers--two surgeons and a hospital worker--infected with
      CCHF virus in Pakistan who were treated with oral ribavirin 4 g/day for four
      days, then 2.4 g/day for six days. Intravenous ribavirin was unavailable. All
      three patients were severely ill with low platelet and white-cell counts, raised
      aspartate transaminase and evidence of impaired haemostasis. Based on published
      reports, all had an estimated probability of death of 90% or more. The patients
      became afebrile, and their haematological and biochemical abnormalities returned
      to normal within 48 h of ribavirin treatment; all made a complete recovery, and
      developed IgG and IgM antibody to CCHF virus. Our experience with ribavirin
      treatment is encouraging, but does not constitute evidence of efficacy. Given the
      difficulties in gathering adequate treatment data, we propose a consensus
      protocol for both intravenous and oral treatment of CCHF. This protocol could be
      distributed to key medical personnel in areas endemic for CCHF and used to
      provide a firm basis for effective treatment recommendations.

PMID- 7637479
TI  - Efficacy trial of malaria vaccine SPf66 in Gambian infants.
AB  - SPf66 malaria vaccine is a synthetic protein with aminoacid sequences derived
      from pre-erythrocytic and asexual blood-stage proteins of Plasmodium falciparum.
      SPf66 was found to have a 31% protective efficacy in an area of intensive malaria
      transmission in Tanzanian children, 1-5 years old. We report a randomised, double
      blind, placebo-controlled trial of SPf66 against clinical P falciparum malaria in
      Gambian infants. 630 children, aged 6-11 months at time of the first dose,
      received three doses of SPf66 or injected polio vaccine (IPV). Morbidity was
      monitored during the following rainy season by means of active and passive case
      detection. Cross-sectional surveys were carried out at the beginning and at the
      end of the rainy season. An episode of clinical malaria was defined as fever (>
      or = 37.5 degrees C) and a parasite density of 6000/microL or more. Analysis of
      efficacy was done on 547 children (316 SPf66/231 IPV). No differences in
      mortality or in health centre admissions were found between the two groups of
      children. 347 clinical episodes of malaria were detected during the three and a
      half months of surveillance. SPf66 vaccine was associated with a protective
      efficacy against the first or only clinical episode of 8% (95% CI -18 to 29, p =
      0.50) and against the overall incidence of clinical episodes of malaria of 3%
      (95% CI -24 to 24, p = 0.81). No significant differences in parasite rates or in
      any other index of malaria were found between the two groups of children. The
      findings of this study differ from previous reports on SPf66 efficacy from South
      America and from Tanzania. In The Gambia, protection against clinical attacks of
      malaria during the rainy season after immunisation in children 6-11 months old at
      time of the first dose was not achieved.

PMID- 7637482
TI  - Glomerulonephritis after human parvovirus infection in homozygous sickle-cell
      disease.
AB  - Glomerulonephritis with proteinuria of sufficient degree to manifest the
      nephrotic syndrome followed aplastic crises induced by human parvovirus (B19) in
      seven patients with homozygous sickle-cell disease, within 7 days in five
      patients and 6-7 weeks in two. Segmental proliferative glomerulonephritis was
      found in all four patients who underwent acute renal biopsies and focal segmental
      glomerulosclerosis was found in the fifth patient who had a biopsy 4 months
      later. One patient recovered completely, one died in chronic renal failure after
      3 months, and the others had impaired creatinine clearance, four with continuing
      proteinuria.

PMID- 7637484
TI  - Tenidap.

PMID- 7637483
TI  - Symptoms, signs, and diagnosis of schizophrenia.

PMID- 7637486
TI  - Vesico-ureteric reflux, urinary-tract infection, and renal damage in children.

PMID- 7637487
TI  - Last days of Health Secretary's honeymoon?

PMID- 7637485
TI  - Effect of changing the stillbirth definition on evaluation of perinatal mortality
      rates.
AB  - The perinatal mortality rate is widely used as a summary statistic for evaluating
      the effectiveness of perinatal care. Since October, 1992, it has been a legal
      requirement in England and Wales to register fetal deaths at 24-27 completed
      weeks of gestation as stillbirths (in addition to those after 28 weeks), thereby
      altering the definition of perinatal death. In a cohort analysis of all babies
      born to women resident in Wales during 1993, we assessed whether the revised
      definition of perinatal mortality rate more appropriately measures effectiveness
      of care. There were 36,793 births and 313 perinatal deaths (221 stillbirths, 92
      early neonatal deaths). At 24-27 weeks' gestation there were 59 (39%) survivors
      and 93 deaths (52 stillbirths, 36 neonatal deaths [28 early, eight late], and 5
      postneonatal deaths). 119 babies had a birthweight below 500 g; one survived and
      24 were perinatal deaths. Of the 36 late neonatal deaths all were attributed to
      perinatally related events. Increased survival of infants at 24-27 weeks'
      gestation emphasises the importance of including all these infants in the
      perinatal mortality rate, but it would be a more useful measure of the
      effectiveness of perinatal care if it excluded babies below 500 g, and included
      late neonatal deaths.

PMID- 7637488
TI  - Japan targets public health research.

PMID- 7637489
TI  - Living with HUGO.

PMID- 7637490
TI  - Primary relapse of acute lymphatic leukaemia in anterior segment of eye.

PMID- 7637491
TI  - The promiscuous B27 hypothesis.

PMID- 7637492
TI  - Anticonvulsants for eclampsia.

PMID- 7637493
TI  - Anticonvulsants for eclampsia.

PMID- 7637494
TI  - Anticonvulsants for eclampsia.

PMID- 7637495
TI  - New isoniazid/ethionamide resistance gene mutation and screening for multidrug
      resistant Mycobacterium tuberculosis strains.

PMID- 7637496
TI  - Vitamin A and measles vaccination.

PMID- 7637497
TI  - Vitamin A and measles vaccination.

PMID- 7637498
TI  - Poliomyelitis outbreak in Zaire.

PMID- 7637499
TI  - Systemic morbidity in patients with isolated idiopathic retinal vasculitis.

PMID- 7637500
TI  - Renal allograft rejection controlled by photopheresis.

PMID- 7637501
TI  - Eugenics in China.

PMID- 7637502
TI  - Eugenics in China.

PMID- 7637503
TI  - Eugenics in China.

PMID- 7637504
TI  - Eugenics in China.

PMID- 7637505
TI  - Eugenics in China.

PMID- 7637506
TI  - Omar del Pozo Marrero: physician prisoner of conscience.

PMID- 7637507
TI  - Mental health in Japan.

PMID- 7637508
TI  - Management of groin strain.

PMID- 7637509
TI  - Tobacco, history, and the AMA.

PMID- 7637510
TI  - Tobacco, history, and the AMA.

PMID- 7637511
TI  - Management of groin strain.

PMID- 7637512
TI  - Growth of Helicobacter pylori in candle jar.

PMID- 7637513
TI  - Helicobacter heilmannii and gastric cancer.

PMID- 7637514
TI  - Urinary CA 19.9 as marker for bladder cancer.

PMID- 7637515
TI  - Methicillin-resistant Staphylococcus aureus (MRSA) in the community.

PMID- 7637516
TI  - Methicillin-resistant Staphylococcus aureus (MRSA) in the community.

PMID- 7637517
TI  - Improved detection of Escherichia coli O157.

PMID- 7637518
TI  - Prevention of atelectasis during general anaesthesia.

PMID- 7637519
TI  - Absence of association of angiotensinogen gene T235 allele with increased risk of
      coronary heart disease in Japanese.

PMID- 7637520
TI  - Influenza types and patient population.

PMID- 7637521
TI  - Tetris and physician's performance state.

PMID- 7637522
TI  - Experimental leprosy in monkeys. II. Longitudinal serological observations in
      sooty mangabey monkeys.
AB  - In this study, 11 SMM were grouped and inoculated with differing doses of SMM
      origin Mycobacterium leprae (ML) between 4.5 x 10(8) and 1 x 10(9) by either
      combined IV/IC routes or by IV or IC route alone. The combined route was the most
      effective in eliciting progressive, disseminated LL leprosy. In all, 6 of 7 SMM
      inoculated by the combined routes developed leprosy requiring treatment at some
      point. Only 1 of 4 inoculated by a single route developed persisting leprosy
      requiring chemotherapy. Either no disease or spontaneous regression of initial
      disease occurred in the other 3 animals inoculated by a single route. Doses in
      excess of 1 x 10(9) ML were more effective than lesser doses. An association was
      observed between the development of IgG anti-PGL-I ELISA OD values and resistance
      to leprosy and between IgM anti-PGL-I and leprosy progression or susceptibility.
      Serum PGL-I antigen levels, determined by dot ELISA, paralleled disease severity
      longitudinally. High positive OD values of anti-LAM IgG prior to ML inoculation
      were observed in the majority of leprosy-susceptible SMM in contrast to negative
      levels in more resistant animals. Anti-LAM IgG OD values exceeded the positive
      cut-off point after inoculation in 5 of 11 SMM; 3 of these 5 had concurrent
      detectable serum levels of PGL-I antigen.

PMID- 7637523
TI  - Classification of leprosy cases under field conditions in Bangladesh. I.
      Usefulness of skin-smear examinations.
AB  - In 2 non-governmental organization projects in Bangladesh 244 new leprosy
      patients were classified in the field according to clinical criteria. Skin smears
      were taken at 4 standardized sites and at the most active peripheral lesion,
      where a biopsy was also taken. Comparison of the clinical field classification
      with the results of the skin smears and biopsies gives a sensitivity of 92.1% for
      the clinical criteria, but a specificity of only 41.3%. The skin-smear results,
      on the other hand, have a sensitivity of 88.4% and a specificity of 98.1%. Thus,
      skin smears may contribute considerably to the operational classification of
      leprosy patients under field conditions. Quality control of the peripheral
      laboratory is essential. Appropriate site selection for the smear taking will
      also contribute to increased performance. Analysis of the skin-smear results
      suggests that the policy of taking smears at standardized sites should be
      abandoned in favour of the earlobes and active peripheral lesions.

PMID- 7637524
TI  - Classification of leprosy cases under field conditions in Bangladesh. II.
      Reliability of clinical criteria.
AB  - In 2 non-governmental organization projects 244 new leprosy patients in
      Bangladesh were classified in the field according to clinical criteria i.e.
      number of skin lesions and number of enlarged nerves. Comparison of these
      classification results with the results of skin smears and biopsies yielded a
      sensitivity (for detection of a MB case) of 92.1%, but the 'unconfirmed MB rate'
      amounted to 52.6%. In order to improve the reliability of the operational
      classification, several additional clinical criteria were investigated. It was
      found that neither the presence of anaesthesia in the skin lesions nor the
      presence of grade 2 disabilities or peripheral anaesthesia or voluntary muscle
      testing (VMT) impairment contributed to an improved classification. Counting the
      number of body areas showing signs of leprosy, which had proven very useful in
      other programmes, did not result in a more reliable classification in the 2
      projects in Bangladesh. The presence of clinical signs of lepromatous leprosy,
      more specifically nodules or diffuse infiltration, could be a useful addition to
      the classification criteria. If the sensitivity must remain higher than 90%, the
      lowest 'unconfirmed MB rate' obtainable in Bangladesh, using clinical criteria
      only, is 46.4%, for a sensitivity of 91.0%. However, the inclusion of skin-smear
      results in the classification criteria could improve the sensitivity to 96.6% and
      lower the 'unconfirmed MB rate' to 40.3%. A reduction in MB overclassification
      will result in more efficient and more cost-effective leprosy control programmes.

PMID- 7637525
TI  - The efficacy of podiatric orthoses as an adjunct to the treatment of plantar
      ulceration in leprosy.
AB  - This study examines the outcome of a management approach to plantar ulceration
      secondary to leprotic neuropathy. Locally-available resources were used to
      produce podiatric orthoses which were supplied to an experimental group. The
      effects on healing time and quality of healing were compared with a control
      group. Both groups were ambulant (the programme sought not to interfere with
      socioeconomic independence). Using standard nonparametric methods of analysis, it
      was demonstrated that the effects on healing rate, attributed to the experimental
      intervention, were highly significant. Over a 7-month period, 57% of the
      experimental group ulcers healed, while only 12.5% of the control group ulcers
      healed. The experimental intervention also demonstrated a positive effect on the
      quality of ulcer healing. This effect was not reflected in the control group.

PMID- 7637527
TI  - A method for texture discrimination in the sole of the foot. A preliminary
      communication.
AB  - A new method for testing sensibility in the sole of the foot is described. In
      this method the ability to distinguish different surfaces while walking is
      assessed. This dynamic, functional and more objective test is recommended as an
      additional tool to evaluate sensibility in the sole of the foot.

PMID- 7637528
TI  - Achieving multidrug therapy for all leprosy patients--ILEP Medical Bulletin.

PMID- 7637526
TI  - Estimating the size of the leprosy problem: the Bangladesh experience.
AB  - Assessing the size of the leprosy problem in a country is an important but
      difficult issue for the purpose of programme planning. Different methods have
      been proposed but often estimates have proved to be very different from reality.
      We have attempted to address this issue in Bangladesh, a country where official
      estimates are more than 5 times greater than the registered number of leprosy
      cases. A combination of methods, including surveys, data from leprosy control
      programmes and local knowledge based on the Delphi techniques have been combined
      to construct an estimate of the total number of cases in Bangladesh. This figure
      (173,196) is only 10% greater than the official estimate (136,000). It will be
      possible over the next few years to see how close this figure is to reality
      through data obtained from the National Leprosy Control Programme which is now
      rapidly developing to cover the whole country.

PMID- 7637529
TI  - Concomitant occurrence of leprosy and tuberculosis: leprosy vaccine, a myth or
      reality?

PMID- 7637530
TI  - Inoculation of the Mycobacterium leprae into the hamster cheek pouch.

PMID- 7637531
TI  - A case of relapsed borderline-lepromatous (BL) leprosy following 27 months of
      multiple drug therapy, Bhutan.

PMID- 7637532
TI  - Training in leprosy: does the current strategy need revision?

PMID- 7637533
TI  - Experimental leprosy in monkeys. I. Sooty mangabey monkeys: transmission,
      susceptibility, clinical and pathological findings.
AB  - A total of 31 sooty mangabey monkeys (SMM) (Cercocebus torquatus atys) inoculated
      by various routes with differing numbers of SMM-origin Mycobacterium leprae (ML)
      and 4 SMM inoculated with human-origin ML were observed for 4-12 years. SMM
      origin ML was more pathogenic in SMM than human-origin ML. The spectrum of
      disease ranged from indeterminate to borderline and lepromatous in different
      animals. Some animals developed pure neural leprosy. Erythema nodosum leprosum
      (SNL) was also observed. Combined intravenous/intracutaneous (IV/IC) routes of
      inoculation more effectively induced advancing, disseminated lepromatous forms of
      leprosy; IV or IC routes alone were less effective at comparable doses. Total
      IV/IC doses of SMM-origin ML equal to or greater than 5 x 10(8), with morphologic
      indices (MIs) ranging from 5 to 10%, produced advancing, disseminated LL leprosy
      in 92% of SMM. Lower IV/IC doses and inoculations by a single IV or IC route
      produced fewer leprosy infections and more spontaneous regressions. As a species,
      captive SMM are highly susceptible to experimental leprosy and provide an
      excellent model for the longitudinal study of leprosy.

PMID- 7637534
TI  - Growth-related signaling as a target of toxic insult in vascular smooth muscle
      cells: implications in atherogenesis.
AB  - Aberrant smooth muscle cell proliferation is a focal point in the genesis and
      progression of atherosclerosis. To date, limited information is available on the
      molecular and cellular basis of the atherogenic response and the potential
      contribution of environmental chemicals to the overall process. This review
      highlights major findings in this laboratory on the mechanism(s) responsible for
      the acquisition of a proliferative phenotype in vascular smooth muscle cells
      following repeated cycles of treatment with allylamine and benzo(a)pyrene, known
      atherogenic chemicals. These agents share the ability to induce and promote
      aberrant proliferative behavior in smooth muscle cells, but appear to interfere
      with distinct molecular targets.

PMID- 7637535
TI  - Bone-specific alkaline phosphatase activities in plasma and callus during
      callotasis in rabbits.
AB  - Using the rabbit as an animal model, the changes of enzymatic activities of bone
      specific alkaline phosphatase (ALP) in plasma and in the callus during callotasis
      were studied. Bone-specific ALP activities were measured by the wheatgerm
      agglutinin precipitation method. Distractions were performed on different groups
      of animals commencing on 3rd, 5th and 7th day after osteotomy. Bone-specific ALP
      activities in the plasma of all these groups dropped significantly on first few
      days compared with those values before osteotomy. However, when distraction was
      started, the plasma bone-specific ALP rose progressively until day 35 and resumed
      normal gradually until day 70. Immediate rises in enzymatic activities after
      distractions were observed in the 5th- and 7th-day treating groups but not in the
      3rd-day treating group. The bone-specific ALP activities in the callus samples
      also increased until day 35 and gradually decreased. With the plasma bone
      specific ALP as an indicator of the biological activities of the osteoblasts, the
      effect of external mechanical stimulation in a form of the tension stress on the
      biological tissue is well demonstrated in this study.

PMID- 7637536
TI  - Sustained hyperhydration with glycerol ingestion.
AB  - Heavy exercise lasting more than three hours tends to result in dehydration, as
      the fluid intake is less than fluid loss by sweat and urine. Dehydration as small
      as one percent of body weight has been reported to decrease work capacity. In
      present and previous studies insensible water loss and sweat are assumed to be
      the same in both control and experimental conditions. Fluid intake less urine
      volume is utilized as an indicator of euhydration, hypohydration, or
      hyperhydration. Previous studies involving glycerol intake describe
      hyperhydration for 4.5 to 8 hours. The objective of this study was to keep
      subjects hyperhydrated (retention of water) for 32 or 49 hours. The experimental
      protocol involved ingestion of a large volume of fluid (39.2 or 51.1 ml/kg/d)
      with glycerol (2.9 to 3.1 g/kg/d) and without glycerol. In both Series I (49 h)
      and Series II (32 h) experiments, the intake of glycerol resulted in smaller
      urine volumes. This study demonstrates it is possible to keep human subjects
      hyperhydrated for extended periods of time and thereby reduce the amount of fluid
      consumption necessary just prior to or during bouts of negative fluid balance
      situations.

PMID- 7637537
TI  - Effect of diet on lignans and isoflavonoid phytoestrogens in chimpanzees.
AB  - Diphenolic compounds belonging to the classes of lignans and isoflavonoids have
      been identified in urine of man and animals, including the chimpanzee. Some of
      these compounds, formed by intestinal bacteria from plant lignans and
      phytoestrogens, have been shown in animal studies to exhibit biological
      activities that suggest they could function as cancer-protective compounds. The
      effect of diet on urinary excretion of these compounds in the adult male
      chimpanzee has been studied. It was found that the chimpanzees consuming their
      regular food excreted large amounts of the isoflavonoid phytoestrogens, equol
      (mean +/- SE) (127.5 +/- 34.0 nmol/mg cr.) and daidzein (20.7 +/- 9.0 nmol/mg
      cr.) and the lignan, enterolactone (14.1 + 3.5 nmol/mg cr.). Small amounts of the
      lignan, enterodiol, (0.4 +/- 0.2 nmol/mg cr.) were also excreted. On all other
      four test diets (high protein, high carbohydrate, high vegetable, and high fat),
      the excretion was less, particularly on a high fat diet where the excretion of
      all diphenolic compounds was reduced by more than 90% to a level observed in
      omnivorous human subjects or women with breast cancer. These results suggest that
      diet profoundly influences the excretion of both animal lignans and
      phytoestrogens in urine. Because non-human primates are particularly resistant to
      mammary and genital carcinoma on estrogen treatment, the present data suggest
      that the very high levels of phytoestrogens and lignans as found during exposure
      to the regular diet may partially account for why these primates are so resistant
      to hormonal manipulations to induce cancer.

PMID- 7637538
TI  - Evaluation of immune parameters in depressed patients.
AB  - The association between depression and altered immunological activities has
      repeatedly been suggested, but experimental data show contradictory results. In
      this work, cellular and humoral immunological activities were evaluated in
      patients presenting major depression, unipolar subtype. Natural killer cell
      activity (NKCA) was significantly reduced in patients as compared to healthy
      controls (p < 0.001). However, lymphocyte mitogenic responses and immunoglobulin
      titers (IgG, IgM, and IgA) were similar for all samples. Hematological, hormonal,
      and nutritional variables presented normal values in patients and in controls. A
      familial history of depression was related to lower NKCA and higher
      phytohemagglutinin responses (p < 0.01). These data suggest possible differential
      inhibition of cellular immune responses in depressed patients.

PMID- 7637539
TI  - Decrease of the pool of amino acids adsorbed on blood cell membranes caused by
      starvation in rats.
AB  - The effect of 24 h starvation on the pool of amino acids adsorbed on the blood
      cell membranes was determined in Wistar rats. Aortic and iliac blood was
      analysed. 24 h starvation induced a significant decrease in the combined
      essential amino acids adsorbed on the blood cell membranes, in both arterial and
      venous blood, without affecting whole-blood levels (adsorbed + non-adsorbed). The
      same tendency was extended to most of the individual amino acids. This finding
      indicates that this pool of adsorbed amino acids has a rapid turnover and
      probably plays a physiological role in a situation of exogenous food deprivation.

PMID- 7637541
TI  - An investigation on the role of plasma and serum opsonins on the internalization
      of biodegradable poly(D,L-lactic acid) nanoparticles by human monocytes.
AB  - We demonstrate here that polyethylene glycol (PEG) 6,000 protects biodegradable
      poly(D,L-lactic acid) nanoparticles (PLA NP) from extensive uptake by monocytes
      in plasma. These results are in agreement with those previously obtained with PEG
      20,000 which reduced the uptake of PLA NP by human monocytes in phosphate
      buffered saline and plasma, and prolonged the NP circulation time in vivo. The
      coating efficiency of PEG 6,000 and 20,000 was substantially decreased in serum.
      The difference between the uptake of plain and coated NP clearly reappeared for
      PEG 20,000-coated NP in heat inactivated serum and in IgG-depleted serum. We
      suggest that typical plasma proteins, heat labile serum proteins (e.g. complement
      components) and IgG are involved in the opsonization of plain and coated PLA NP.
      Other proteins previously found to adsorb onto these NP, namely albumin and
      apolipoprotein E, did not appear to directly influence the uptake process.

PMID- 7637540
TI  - Differential effects of spermine on phosphatidylinositol 3-kinase and
      phosphatidylinositol phosphate 5-kinase.
AB  - The metabolism of phosphoinositides plays an important role in the signal
      transduction pathways. We report here that naturally occurring polyamines affect
      the activities of phosphatidylinositol (PI) 3-kinase and PI 4-phosphate (PIP) 5
      kinase differently. While polyamines inhibited the PI 3-kinase activity, they
      stimulated the activity of PIP 5-kinase in the order of spermine > spermidine >
      putrescine. Spermine inhibited the PI 3-kinase activity in a concentration
      dependent manner with an IC50 of 100 microM. On the other hand, spermine (5 mM)
      stimulated the activity of PIP 5-kinase 2-3 fold. Kinetic studies of spermine
      mediated inhibition of PI 3-kinase revealed that it was noncompetitive with
      respect to ATP. The effect of Mg2+ and PIP2 concentration on kinase activity was
      sigmoidal, with spermine inhibiting PI 3-kinase activity at all PIP2
      concentrations. While 1 mM calcium stimulated PI 3-kinase activity at submaximal
      concentrations of Mg2+ (1.25 mM), inhibition was observed at optimal
      concentration of Mg2+ (2 mM). We propose that spermine may modulate the cellular
      signal by virtue of its differential effects on phosphoinositide kinases.

PMID- 7637542
TI  - The effects of a selective alpha-1 adrenergic blockade on the activity of adipose
      tissue lipoprotein lipase in female hamsters.
AB  - Lipoprotein lipase, is an enzyme responsible for the hydrolysis of
      triacylglycerols at the surface of endothelial cells. Its regulation is not
      completely elucidated and seems, among other things, under the influence of the
      sympathetic nervous system. The adrenergic regulation of lipoprotein lipase
      activity is complex and the alpha 1 adrenergic pathway appears involved in this
      regulation. In the present study, adipose tissues of female hamsters are
      investigated following a single injection of doxazosin and phenylephrine and are
      compared to controls for the activity of lipoprotein lipase. After an acute
      treatment with a selective alpha 1 antagonist (doxazosin), lipoprotein lipase
      activity was decreased in the parametrial white adipose tissue and increased in
      brown adipose tissue (p < or = 0.05). Moreover, a treatment with phenylephrine,
      an alpha 1 adrenergic agonist, increased the activity of lipoprotein lipase, in
      the parametrial fat pad only. On the other hand, the activity of lipoprotein
      lipase in heart and in skeletal muscle was not modified by an alpha 1 stimulation
      or blockade. In this study, calcium and norepinephrine did not appear involved in
      the regulation of lipoprotein lipase activity. On the contrary, the increase of
      plasma glycerol after an acute treatment with doxazosin suggests that the
      lipolytic activity of white adipose tissue could be involved in the decrease of
      lipoprotein lipase activity in the parametrial white adipose tissue.

PMID- 7637543
TI  - Effect of gluten exorphins A5 and B5 on the postprandial plasma insulin level in
      conscious rats.
AB  - The effect of exogenous opioid peptides, gluten exorphins A5 and B5, which were
      isolated from the enzymatic digest of wheat gluten, on the postprandial insulin
      level were examined in rats. The oral administration of gluten exorphin A5 at a
      dose of 30 mg/kg w. potentiated the postprandial plasma insulin level and the
      effect was reversed by naloxone. The administration of gluten exorphin B5 showed
      a similar effect at a higher dose (300 mg/kg w). Furthermore, intravenous
      administration of gluten exorphin A5 at a dose of 30 mg/kg w. also stimulated the
      postprandial insulin release. The fact that orally and intravenously administered
      gluten exorphin A5 stimulates insulin release suggests that it modulates
      pancreatic endocrine function by the action after the absorption rather than
      within the the gastrointestinal tract.

PMID- 7637544
TI  - Agmatine: a novel endogenous vasodilator substance.
AB  - The purpose of the study was to investigate the effects of agmatine, an
      endogenous clonidine-displacing substance (CDS), on systemic hemodynamics in the
      anesthetized rat. Bolus intravenous (i.v.) injections of agmatine decreased
      systemic arterial pressure (SAP) and systemic vascular resistance in a dose
      dependent manner. The development of acute tachyphylaxis to the systemic
      vasodepressor response to agmatine did not induce cross-tachyphylaxis to the
      systemic vasodepressor responses to bradykinin, isoproterenol and nitroglycerin.
      The present data demonstrate agmatine, as a CDS and agonist for imidazoline (I)
      receptors, possesses marked systemic vasodilator activity in the rat. The present
      data suggest that activation of I receptors may represent a novel mechanism of
      vasodilation in vivo.

PMID- 7637545
TI  - Adrenotensin: an ADM gene product with the opposite effects of ADM.
AB  - The purpose of the present study was to investigate the effects of putative
      products of the ADM gene, other than ADM including, prodepin, proADM45-92 and
      proADM153-185 on cat pulmonary arterial (PA) rings with or without precontraction
      with U46619. Addition of proADM153-185 (3 x 10(-10)-10(-6) M) increased tension
      in a concentration-dependent manner in cat PA rings without precontraction. When
      vessels were precontracted with U46619, ADM(3 x 10(-10)-10(-6) M) produced a
      concentration-dependent vasorelaxant response, whereas proADM153-185 produced a
      weak concentration-dependent contractile response. Prodepin and proADM45-92 up to
      10(-6)M had no activity on PA rings. Since proADM153-185, similar to ADM, would
      be expected to be released in free form following endopeptidase-induced cleavage,
      the present data suggest proADM undergoes proteolytic processing to release
      peptides with divergent vascular effects. Thus, the present data also suggest
      that proADM153-185 may represent a novel product of the ADM gene and term this
      putative new substance "adrenotensin".

PMID- 7637546
TI  - Sandostatin inhibits development of medial proliferation of pulmonary arteries in
      a rat model of pulmonary hypertension.
AB  - We investigated the effects of subcutaneous administration of 50 and 100
      micrograms/kg/day of sandostatin on monocrotaline-induced medial proliferation of
      pulmonary arteries and right ventricular overload in rats. In a dosage of 100
      micrograms/kg/day, sandostatin significantly reduced right ventricular systolic
      pressure, the mass ratio of the right ventricular free wall to the left
      ventricle, the right ventricular wall thickness, the right ventricular myofiber
      diameter, the percent medial pulmonary artery thickness, the percent area of
      smooth muscle cell, and proliferating cell nuclear antigen activity. Our results
      suggest that sandostatin inhibits development of medial proliferation of
      pulmonary arteries and right ventricular overload in a dosage of 100
      micrograms/kg/day.

PMID- 7637547
TI  - Endothelin-1 and endothelin-3 modulate dopaminergic neurons through different
      mechanisms.
AB  - Novel vasoconstrictor peptides, endothelin-1 (ET-1) and endothelin-3 (ET-3), are
      also known as neuropeptides or neuromodulators. When either ET-1 or ET-3 was
      administered to the rat striatum via a microinjection needle, the dopamine
      release from the striatum dose-dependently increased. Pretreatment with a
      glutamate receptor blocker, glutamate diethyl ester hydrochloride, inhibited the
      dopamine release induced by ET-3, whereas it further enhanced the dopamine
      release by ET-1. This suggests that ET-1 directly induces the dopamine release,
      whereas the action of ET-3 is mediated by glutamate receptors. We postulate that
      this difference may result from the different distributions of endothelin
      receptors: ETA receptors may be present on the dopaminergic neurons, but ETB
      receptors on the glutamatergic neurons.

PMID- 7637548
TI  - The attenuation of suppression of motility by triazolam in the conditioned fear
      stress task is exacerbated by ethanol in mice.
AB  - We investigated whether triazolam attenuated the suppression of motility in the
      conditioned fear stress task in mice and whether ethanol modified the effects of
      triazolam. When mice were placed 24 hours later (retention test) in the same
      environment in which they had previously been exposed to an electric foot shock
      (training), they exhibited a marked suppression of motility (conditioned fear
      stress). Triazolam (0.01-0.1 mg/kg, s.c.), administered before training,
      attenuated the suppression of motility in the conditioned fear stress task in a
      dose-dependent manner, without affecting the sensitivity to an electric foot
      shock. The doses of triazolam that attenuated the suppression of motility were
      much lower that those of chlordiazepoxide (5-10 mg/kg, s.c.). Neither drug,
      administered before the retention test, attenuated the suppression of motility in
      the conditioned fear stress task. These results suggest that both benzodiazepines
      may inhibit the process of acquisition, but not the process of recall, of memory.
      Ethanol (1 g/kg, p.o.), which, by itself, did not affect either the suppression
      of motility or the sensitivity to an electric foot shock, exacerbated the
      attenuation of the suppression of motility in the conditioned fear stress task
      induced by both triazolam (0.01 mg/kg) and chlordiazepoxide (5 mg/kg). These
      results suggest that ethanol exacerbates the effects of benzodiazepines.

PMID- 7637549
TI  - Stimulation of myofibrillar protein synthesis in hindlimb suspended rats by
      resistance exercise and growth hormone.
AB  - The objective of this study was to determine the ability of a single bout of
      resistance exercise alone or in combination with recombinant human growth hormone
      (rhGH) to stimulate myofibrillar protein synthesis (Ks) in hindlimb suspended
      (HLS) adult female rats. Plantar flexor muscles were stimulated with resistance
      exercise, consisting of 10 repetitions of ladder climbing on a 1 m grid (85
      degrees), carrying an additional 50% of their body weight attached to their
      tails. Saline or rhGH (1 mg/kg) was administered 30' prior to exercise, and Ks
      was determined with a constant infusion of 3H-Leucine at 15', 60', 180', and 360'
      following exercise. Three days of HLS depressed Ks approximately 65% and 30-40%
      in the soleus and gastrocnemius muscles, respectively (p < or = 0.05). Exercise
      increased soleus Ks in saline-treated rats 149% 60' following exercise (p < or =
      0.05), decaying to that of non-exercised animals during the next 5 hours.
      Relative to suspended, non-exercised rats rhGH+exercise increased soleus Ks 84%,
      108%, and 72% at 15', 60' and 360' following exercise (p < or = 0.05).
      Gastrocnemius Ks was not significantly increased by exercise or the combination
      of rhGH and exercise up to 360' post-exercise. Results from this study indicate
      that resistance exercise stimulated Ks 60' post-exercise in the soleus of HLS
      rats, with no apparent effect of rhGH to enhance or prolong exercise-induced
      stimulation. Results suggests that exercise frequency may be important to
      maintenance of the slow-twitch soleus during non-weightbearing, but that the
      ability of resistance exercise to maintain myofibrillar protein content in the
      gastrocnemius of hindlimb suspended rats cannot be explained by acute stimulation
      of synthesis.

PMID- 7637550
TI  - Inhibition of extracellular ATP degradation in endothelial cells.
AB  - The plasma membrane ATPase on the human umbilical vein endothelial cell line
      (ECV304) was demonstrated to be an ecto-enzyme. Hydrolysis of ATP was measured by
      monitoring the appearance of inorganic phosphorus. Hydrolysis of extracellular
      ATP was insensitive to oligomycin, vanadate, ouabain and N-ethylmaleimide,
      compounds that inhibit the intracellular ion pumping ATPases. Beta
      Glycerophosphate (1-10 mM) or p-nitrophenyl phosphate (1-10 mM) did not inhibit
      hydrolysis of ATP, ruling out the involvement of non-specific phosphatases.
      Enzyme activity in buffer that had previously been incubated with cells was < 7%,
      showing that the enzyme activity measured did not result from release of
      intracellular enzymes. Consistent with this, the cell preparations used were
      estimated to be > 95% intact as judged by release of cytosolic enzyme lactate
      dehydrogenase. The enzyme activity was Ca2-/Mg2- dependent. Gramicidin S (20
      microM), suramin (100-300 microM), chlorpromazine (250 microM), trifluoperazine
      (50-250 microM), and thioridazine (100 microM) inhibited the hydrolysis of ATP (3
      mM) by 45-80%. The percentage inhibition produced by these substances was not
      altered in the presence of a concentration of alpha, beta-methylene ADP (10
      microM) which inhibited hydrolysis of AMP (3 mM) by 90%, suggesting that these
      compounds inhibit ecto-ATPase and/or ecto-ADPase. Measurements of absolute
      amounts of ATP released from various tissues, including the heart, have been
      hindered because ATP is rapidly and sequentially hydrolysed to adenosine.
      Identification of compounds that inhibit ATP degradation would prove to be useful
      to overcome this problem and would lead to the development of invaluable
      pharmacological tools in many other aspects of purine research.

PMID- 7637551
TI  - Attenuation of hypoxia-induced increases in ventilation by adenosine antagonists
      in rhesus monkeys.
AB  - The respiratory effects of caffeine and paraxanthine, two xanthine adenosine
      antagonists with phosphodiesterase (PDE) activity, CGS 15943, a non-xanthine
      adenosine antagonist lacking PDE inhibitory activity, and rolipram, a non
      xanthine PDE inhibitor lacking adenosine antagonist activity, were characterized
      in unanesthetized, seated rhesus monkeys exposed to 10% O2 balanced in N2
      (hypoxia). Ventilation was measured continuously by enclosing the monkey's head
      in a fitted helmet and using a pressure-displacement plethysmographic technique.
      Respiratory frequency (f) and minute volume (VE) increased during 15-minute
      periods of hypoxia, and intramuscular administration of caffeine (0.3 and 1.0
      mg/kg), paraxanthine (0.3 and 1.0 mg/kg) and CGS 15943 (0.03 and 0.1 mg/kg)
      attenuated the ventilatory response to hypoxia. In contrast, rolipram (0.003-0.03
      mg/kg) did not significantly alter the ventilatory response to hypoxia. Drug
      effects also were characterized in monkeys exposed to air (normoxia) or 3%, 4%
      and 5% CO2 balanced in air (hypercapnia). Doses of caffeine, paraxanthine or CGS
      15943 that attenuated the ventilatory response to hypoxia had no significant
      effect on f or VE during conditions of normoxia or hypercapnia. The results
      indicate that adenosine may play a major role in the function of peripheral, O2
      sensitive mechanisms during hypoxia.

PMID- 7637552
TI  - 4-Hydroxynonenal formation during ischemia and reperfusion of rat small
      intestine.
AB  - The metabolism and the washout of 4-hydroxynonenal (HNE), a major lipid
      peroxidation product, was determined in jejunal intestine of rats under normoxic,
      ischemic and postischemic conditions. The HNE utilization was by several orders
      higher than the HNE washout. Under ischemic conditions a drastic decrease of HNE
      utilization was found, compared with normoxic and postischemic utilization rates.
      The real flux rate of intracellular HNE formation during ischemia and reperfusion
      of small intestine was for the first time estimated on the basis of tissue HNE
      concentration, HNE utilization rate at defined HNE tissue concentration and HNE
      washout by perfusate circulation. Such estimation led to intestinal HNE formation
      rates of about 20 nmoles/g/min at normoxia, 20 to 40 nmoles/g/min at ischemia,
      100 nmoles/g/min at 10 min of reperfusion and 20 nmoles/g/min at 60 min of
      reperfusion. Therefore, one can conclude that the tissue concentration of HNE
      only partly represents the real HNE formation rate and that the formation rate is
      of particular pathophysiological importance.

PMID- 7637553
TI  - 5-hydroxytryptamine inhibits pressor responses to preganglionic sympathetic nerve
      stimulation in pithed rats.
AB  - 5-Hydroxytryptamine (5-HT) inhibits contractile responses to adrenergic nerve
      stimulation in several blood vessels and organs. We have now investigated the
      potential ability of 5-HT to inhibit the pressor responses caused by
      preganglionic sympathetic stimulation (T7-T9) in pithed rats. Sympathetic
      stimulation (0.03, 0.1, 0.3, 1 and 3 Hz) resulted in frequency-dependent
      increases in diastolic blood pressure; these effects were augmented after i.v.
      treatment with desipramine (50 micrograms/kg). During continuous infusions of 5
      HT (1.8, 3.1, 5.6 and 10 micrograms/kg.min, i.v.), but not of saline, the pressor
      responses were dose-dependently inhibited in both control and desipramine
      pretreated rats; this inhibitory effect of 5-HT was significantly more pronounced
      at lower frequencies of stimulation. In contrast, the above infusions of 5-HT did
      not inhibit the pressor responses induced by i.v. bolus injections of exogenous
      norepinephrine (up to 3 micrograms/kg). Taken together, the above findings
      suggest an operative 5-HT-induced prejunctional inhibition of sympathetic nerve
      activity on the systemic vasculature in vivo.

PMID- 7637554
TI  - Oral administration of homocysteine leads to increased plasma triglycerides and
      homocysteic acid-additional mechanisms in homocysteine induced endothelial
      damage?
AB  - Increased plasma homocyst(e)ine is strongly correlated with occlusive arterial
      diseases. A series of different hypotheses have been reported including
      involvement of free oxygen radicals and therefore oxidative stress. We determined
      plasma homocyst(e)ine and homocysteic acid levels after oral low dose
      homocysteine thiolactone administration to rats for a period of six weeks. Plasma
      levels of homocyst(e)ine and triglycerides were significantly elevated in the
      group fed homocysteine thiolactone. GC/MS determination of ketone body formation
      showed that the underlying mechanism for the increase of triglycerides seems to
      be inhibition of fatty acid oxidation. Homocysteic acid was detected in the
      experimental group exclusively. The present study showing a homocyst(e)ine
      correlated increase of plasma triglycerides by the inhibition of fatty acid
      oxidation may well propose an additional role of triglycerides for vascular
      pathology. The presence of homocysteic acid in the experimental group only would
      support the free oxygen radical hypothesis for the development of vascular
      changes but homocysteic acid as a potent neurotransmitter could play an
      independent role in the pathogenesis.

PMID- 7637555
TI  - The involvement of the peripheral 5-HT2A receptor in peripherally administered
      serotonin-induced hyperglycemia in rats.
AB  - The mechanism of the hyperglycemic response to intraperitoneally administered
      serotonin (5-HT) was studied in rats. 5-HT i.p.-induced hyperglycemia was
      strongly antagonized by the 5-HT2A receptor antagonist ketanserin. 5-HT did not
      affect the serum insulin levels and increased plasma glucagon levels only at the
      high dose of 10 mg/kg. 5-HT dose-dependently induced a remarkable increase in
      plasma adrenaline levels and these effects were antagonized by ketanserin. 5-HT
      induced hyperglycemia was abolished by adrenodemedullation. These results suggest
      that the hyperglycemic effects of 5-HT are closely related to the release of
      adrenaline from the adrenal gland, mediated by 5-HT2A receptors.

PMID- 7637556
TI  - Leukotriene B4 stimulation of an early elevation of phosphatidic acid mass in
      human neutrophils.
AB  - The signal transduction pathway of leukotriene B4 involves phospholipase D
      activation in cytochalasin B-primed neutrophils, but leukotriene B4 stimulation
      of increased phosphatidic acid mass in neutrophils has not been demonstrated.
      Employing the NIH Image program, we have examined the effect of leukotriene B4 on
      phosphatidic acid mass in human neutrophils incubated with or without
      cytochalasin B. Our results show that 0.15 microM leukotriene B4 without
      cytochalasin B was capable of increasing phosphatidic acid mass in neutrophils by
      2-fold after 5 s, 2.5-fold after 1 min, and 2-fold after 5 min incubation.
      Leukotriene B3, leukotriene B4, and leukotriene B5 were equipotent stimuli for
      phosphatidic acid mass elevation. Leukotriene B4 induced phosphatidylethanol
      formation at the expense of phosphatidic acid in cells preincubated with 0.25-1%
      ethanol, indicating phospholipase D activation. Cytochalasin B enhanced
      leukotriene B4 stimulation of phosphatidic acid mass elevation and
      phosphatidylethanol formation. There were no measurable changes in 1,2
      diglyceride mass after 5 s, but a 1.7-fold increase occurred after 1 min and
      declined thereafter. Leukotriene B4 stimulation of [3H]glycerol incorporation
      into phosphatidic acid, diglyceride and phosphatidylinositol was detectable after
      a 1-min incubation, suggesting increased de novo synthesis of these lipids. These
      results suggest that leukotriene B4 stimulation of phospholipase D activity
      contributes to part of the early increased phosphatidic acid mass and that
      combined actions of stimulated phospholipases C and D, and de novo phosphatidic
      acid synthesis contribute to the total increased phosphatidic acid mass.

PMID- 7637557
TI  - Diabetes and proteolysis: effects on carnitine palmitoyltransferase-I and malonyl
      CoA binding.
AB  - Malonyl-CoA binding and malonyl-CoA inhibition of carnitine palmitoyltransferase
      I (CPT-I) were measured in hepatic mitochondria from normal and diabetic rats and
      in protease-treated mitochondria from fed rats to test the hypothesis that
      proteolysis represents a mechanism by which diabetes produces changes in the
      sensitivity of CPT-I to inhibition by malonyl-CoA. As in diabetes, protease
      treatment increased the apparent Ki values for malonyl-CoA. Palmitoyl-CoA greatly
      diminished malonyl-CoA specific binding in the mitochondrial system being
      studied, suggesting strong competition at the malonyl-CoA binding site.
      Proteolysis decreased capacity for specific binding of malonyl-CoA by 60-80%, but
      it had no effect on binding affinity. In contrast, the decreased specific binding
      of malonyl-CoA seen in the diabetic state is accompanied by increased binding
      affinity. Furthermore, observed Kd values differed from Ki values by a factor of
      10 or more, suggesting that measured Kd and Ki may represent different ligand
      protein complexes. These data suggest that alterations in inhibition of CPT-I by
      malonyl-CoA occurring in the diabetic state may involve mechanisms other than
      simple proteolytic removal of malonyl-CoA binding sites.

PMID- 7637558
TI  - The effect of two synthetic phospholipids on cell proliferation and
      phosphatidylcholine biosynthesis in Madin-Darby canine kidney cells.
AB  - The concentration-dependent effects of two different synthetic phospholipids on
      cell proliferation and phosphatidylcholine biosynthesis were compared in Madin
      Darby canine kidney (MDCK) cells. The alkyllysophospholipid 1-O-octadecyl-2-O
      methyl-sn-glycero-3-phosphocholine and the alkylphosphocholine,
      hexadecylphosphocholine, inhibited cell proliferation with half-inhibitory
      concentrations (IC50) of 75 and 135 mumol/L, respectively. The agents also
      inhibited phosphatidylcholine biosynthesis in confluent and proliferating MDCK
      cells. The IC50 of 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphocholine was 40
      mumol/L in confluent cells and 20 mumol/L in proliferating cells, whereas the
      IC50 of hexadecylphosphocholine was higher in both experimental systems (67
      mumol/L in confluent cells and 40 mumol/L in proliferating cells). Further
      experiments revealed that the effect of both agents on phosphatidylcholine
      biosynthesis was reversible and that the inhibition was mediated by translocation
      of the rate-limiting enzyme of this pathway, CTP:phosphocholine
      cytidylyltransferase (EC 2.7.7.15), from membranes to the cytosol, where it is
      inactive. The present findings suggest that the inhibition of phosphatidylcholine
      biosynthesis by both synthetic phospholipids might be related, in part, to their
      antiproliferative effects.

PMID- 7637559
TI  - Iron-catalyzed reaction products of alpha-tocopherol with methyl 13(S)
      hydroperoxy-9(Z),11(E)-octadecadienoate.
AB  - alpha-Tocopherol was reacted with methyl 13(S)-hydroperoxy-9(Z), 11(E)
      octadecadienoate in the presence of an iron-chelate, Fe(III)-acetylacetonate, at
      37 degrees C in benzene. The reaction was carried out either aerobically or
      anaerobically. The main products of alpha-tocopherol under air were isolated and
      identified as two stereoisomers of 4a,5-epoxy-8a-hydroperoxy-alpha-tocopherone,
      four stereoisomers of methyl 9-(8a-dioxy-alpha-tocopherone)-12, 13-epoxy-10(E)
      octadecenoate, four stereoisomers of methyl 11-(8a-dioxy-alpha-tocopherone)-12,13
      epoxy-9(Z)-octadecenoa te, two stereoisomers of methyl 13(S)-(8a-dioxy-alpha-
      tocopherone)-9(Z),11(E)-octadecadienoate, and alpha-tocopherol dimer. Besides the
      8a-(lipid-peroxy)-alpha-tocopherones, two stereoisomers of methyl 11-(alpha
      tocopheroxy)-12(S),13(S)-epoxy- 9(E)-octadecenoate, two stereoisomers of methyl 9
      (alpha-tocopheroxy)-12(S), 13(S)-epoxy-10(E)-octadecenoate, and two isomers of
      methyl (alpha-tocopheroxy)-octadecadienoate were obtained under nitrogen
      atmosphere. The results indicate that the peroxyl radicals from lipid
      hydroperoxides prefer to react with the 8a-carbon radical of alpha-tocopherol and
      the carbon-centered radicals react with the phenoxyl radical of alpha-tocopherol.

PMID- 7637560
TI  - Oxidized cholesterol modulates age-related change in lipid metabolism in rats.
AB  - For three weeks, male Sprague-Dawley rats at either four weeks (young) or eight
      months (adult) of age were pair-fed one of the purified diets free of or
      containing either 0.2% of oxidized cholesterol mixture (cholesterol oxidation
      products) or 0.2% of cholesterol. Although the food intake was similar, dietary
      oxidized cholesterol lowered body weight gain in young rats, but did not increase
      relative liver weight, in contrast to the enlargement seen with dietary
      cholesterol. Oxidized cholesterol, compared to cholesterol, tended to reduce the
      activity of hepatic 3-hydroxy-3-methylglutaryl CoA reductase and cholesterol 7
      alpha-hydroxylase, particularly the latter in aged rats, and prevented the rise
      in the concentration of liver cholesterol at both ages. It also tended to
      increase the activity of hepatic delta 6 desaturase, particularly in young rats.
      Moreover, oxidized cholesterol in relation to cholesterol influenced liver and
      serum lipid concentrations in different ways, and increased lipid peroxidation at
      both ages. The ratio of splenic CD4+/CD8+ T-lymphocytes increased with age, but
      the influence of cholesterol and oxidized cholesterol was comparable. Thus,
      oxidized cholesterol may specifically disturb growth and age-related changes in
      the lipid metabolism in rats.

PMID- 7637561
TI  - Dietary fats rich in saturated fatty acids (12:0, 14:0, and 16:0) enhance
      gallstone formation relative to monounsaturated fat (18:1) in cholesterol-fed
      hamsters.
AB  - To test the possibility that dietary palmitic acid (16:0) may be lithogenic,
      different fats were blended to exchange 18:1 in olive oil with either 16:0 in
      palm stearin, 12:0 + 14:0 in coconut oil, or 14:0 + 16:0 in butterfat. Dietary
      18:2 was held constant at 1.2% energy (en) (with extra safflower oil as needed)
      in these four purified diets containing low fat (11% of total energy) and 0.4%
      cholesterol. A fifth, high-fat diet provided 40% of the total energy as the 16:0
      rich blend. All hamsters fed the low-fat 16:0-rich blend for six weeks developed
      cholesterol gallstones (8/8). Although the gallstone incidence was lower for the
      12:0 + 14:0-rich diet (5/8), the severity of stone formation in affected hamsters
      was equal to that in the low-fat, 16:0-rich group. Mucin accumulation in
      gallbladder bile was often associated with cholesterol gallstones in diets
      containing 16:0, but was minimal in 18:1-rich and 12:0 + 14:0-rich groups.
      Neither the lithogenic index (all > 1.0), plasma lipids, nor liver cholesterol
      was a selective predictor of stone formation. The high-fat, 16:0-rich diet
      actually decreased cholesterol stone incidence (3/8) and severity, but yielded a
      high incidence of pigment stones (5/8). Thus, saturated fat and 16:0 per se were
      not responsible for the exaggerated lithogenesis. Because the antilithogenic 18:1
      rich diet also normalized the 18:2 intake (1.2% en) relative to previous butter
      diets (0.3% en), the potential importance of essential fatty acids (EFA)
      deficiency in the model was tested in a second study by feeding graded amounts of
      18:2 (0.3, 0.6, 0.9, and 1.2% en) as safflower oil in four low-fat, butter-rich
      diets (11% en as fat) without alleviating gallstone incidence or severity. These
      studies indicate that substitution of 18:1 for saturated fatty acids in low-fat
      diets reduces gallstone formation without affecting the lithogenic index.
      Furthermore, intake of 18:2 at or below the EFA requirement does not appear to be
      a major factor in this model.

PMID- 7637562
TI  - Evidence that dietary arachidonic acid increases circulating triglycerides.
AB  - Male Syrian hamsters and male CD-1 mice were fed diets supplemented with ethyl
      esters of oleic, linoleic, arachidonic, and eicosapentaenoic acids (1.1-5%, w/w)
      for 3-4 wk. Plasma and serum triglycerides were significantly higher in the
      arachidonic acid-supplemented animals compared to those in the other
      supplementation groups. Changes in serum insulin and glucose levels did not
      appear to be related to the changes in circulating triglycerides observed in the
      arachidonic acid-supplemented group. These data indicate that dietary arachidonic
      acid elevates circulating triglyceride levels compared to other unsaturated fatty
      acids in hamsters and mice by unknown mechanisms.

PMID- 7637563
TI  - Reduction of hyperlipidemia in hepatoma-bearing rats by dietary fish oil.
AB  - The effect of dietary fish oil on serum lipid levels was studied by comparing it
      with dietary corn oil in Donryu rats subcutaneously implanted with an ascites
      hepatoma cell line (AH109A). The hepatoma-bearing rats exhibited hyperlipidemia
      characterized by a rise in both serum cholesterol and triglyceride levels.
      Increased cholesterogenesis in the host liver and decreased steroid excretion
      into feces are suggested to be responsible for the hepatoma-induced
      hypercholesterolemia, and increased fatty acid mobilization from peripheral
      adipose tissues and decreased triglyceride clearance from the blood circulation
      are considered causes for the hepatoma-induced hypertriglyceridemia. Dietary fish
      oil reduced the hyperlipidemia in these animals, suppressed the hepatoma-induced
      increase in hepatic cholesterogenesis and fatty acid mobilization from adipose
      tissue. Dietary fish oil also tended to increase fatty acid oxidation in the
      liver. Such diverse effects of fish oil may lead to the reduction of the hepatoma
      induced hyperlipidemia. These results suggest that studies on dietary fish oil
      may be warranted in patients with cancer-related hyperlipidemia.

PMID- 7637564
TI  - Dietary fish oils and long-term malaria protection in mice.
AB  - Previous studies indicate a suppressive influence of fish oils on rodent malaria.
      The present work was carried out to study (i) the dose-effect relation between
      dietary fish oils and lethality of primary malaria infection in mice; (ii) the
      modifying influence of vitamin E; and (iii) the effect of previous fish oil
      feeding on parasitemia and lethality of a rechallenge infection. For two or four
      weeks, groups of weanling male mice were fed a standard laboratory diet or one of
      eight purified diets containing various amounts of fish oil (providing 6-21% of
      energy). The diets were prepared with and without vitamin E. After the two- or
      four-week feeding period, the mice were injected intraperitoneally with
      Plasmodium yoelii-infected erythrocytes. Six months after the primary infection
      (four months after discontinuing fish oil feeding), the surviving mice were again
      injected intraperitoneally with parasitized red blood cells (or even better-
      erythrocytes, erythrocytes are used elsewhere). Primary malaria infection was
      lethal in mice fed standard diet alone or with fish oil and vitamin E added. In
      contrast, feeding a fish oil-based diet without vitamin E improved survival to at
      least 70% if the mice had been fed these diets for four weeks. Protection against
      malaria did not seem to be related to the fish oil dose used. Regardless of the
      previous fish oil dose, all the mice surviving the primary infection survived the
      rechallenge infection with low parasitaemias.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7637565
TI  - Dietary deficiency of docosahexaenoic acid impairs vision at low light
      intensities in juvenile herring (Clupea harengus L.).
AB  - In the retina of herring (Clupea harengus L.), rods are recruited from about 8 wk
      after hatching, and from this time there is a linear relationship between the
      number of rods in the photoreceptor cell population and the content of di22:6n-3
      molecular species of phospholipids. Juvenile herring were reared from four weeks'
      post-hatching for 15 wk on either Artemia nauplii deficient in 22:6n-3 or on
      enriched Artemia nauplii containing 4.3% 22:6n-3. The visual performance of the
      fish was then determined at three light intensities (0.01, 0.1, and 1.0 lux) by
      observing their frequency of striking at live Artemia nauplii using infrared
      video recording. Herring reared on the diet containing no 22:6n-3 were less
      active predators, especially at the lowest light intensity where very few strikes
      were observed. The eyes of these fish contained greatly reduced levels of di22:6n
      3 molecular species of total phospholipid, 2.1% vs. 12.0% in fish supplemented
      with 22:6n-3. The contribution of saturated and monounsaturated fatty acids in
      the molecular species of phosphatidylethanolamine (PE), phosphatidylserine (PS),
      and phosphatidylcholine (PC) was virtually unchanged, while 20:5n-3 and 22:5n-3
      largely replaced 22:6n-3. There was an almost complete disappearance of di22:6n-3
      PC, while the amounts of di22:6n-3 PE and PS fell by 18.1 and 20.6% to 2.7 and
      7.6%, respectively. The dipolyunsaturated molecular species di20:5n-3, 20:5n
      3/22:5n-3, and di22:5n-3 made up a substantial part of the deficit. We conclude
      that a dietary deficiency of 22:6n-3 during the period early in rod development
      impairs visual performance such that the fish can no longer feed at low light
      intensities.

PMID- 7637567
TI  - New branched-chain fatty acids from the Senegalese gorgonian Leptogorgia piccola
      (white and yellow morphs).
AB  - Fatty acids from total lipids of the gorgonian Leptogorgia piccola (white and
      yellow morphs), collected from the same area at two different periods with regard
      to the average water temperature, were studied. More than fifty fatty acids were
      identified as methyl esters and N-acyl pyrrolidides by gas chromatography and gas
      chromatography/mass spectrometry. Three new, branched-chain unsaturated fatty
      acids were identified in addition to the unusual 7-methyl-6-hexadecenoic acid,
      namely 10-methyl-6-hexadecenoic, 7,9-dimethyl-6-hexadecenoic, and 10-methyl-6,9
      heptadecadienoic acids. Also 6,9-heptadecadienoic acid was identified. The fatty
      acid patterns of specimens harvested in colder waters were quite different from
      those harvested in warmer waters in that the former contained high amounts of
      methylene-interrupted polyunsaturated acids, including tetracosapolyenoic acids,
      especially 6,9,12,15,18-24:5 (up to 15.8% of the total acid mixture) and
      6,9,12,15,18,21-24:6 (up to 5.3%). Arachidonic acid was, nevertheless, a major
      component in all the fatty acid mixtures studied (13.6-20.5%). Based on gas
      chromatography/Fourier transform infrared experiments, the double bonds were
      assigned the (Z) configuration. Several fatty aldehydes and their dimethyl
      acetals were also detected, of which the most abundant was octadecanal.

PMID- 7637568
TI  - The rare Caribbean sponge Leucosolenia canariensis: phospholipid fatty acids and
      sterols.
AB  - The phospholipid fatty acid composition of the Calcarean sponge Leucosolenia
      canariensis was studied, and no delta 5,9 fatty acids were detected. These
      results are in contrast to the phospholipids from sponges belonging to the class
      Demospongiae where delta 5,9 fatty acids are predominant. Odd branched-chain
      fatty acids between 17 and 19 carbons accounted for 26% of the total fatty acids
      of L. canariensis, while straight-chain fatty acids between 16 and 22 carbons
      accounted for 61% of the total fatty acid composition. The sterol composition of
      L. canariensis is also reported, and only delta 5,7,22 sterols were observed.

PMID- 7637566
TI  - Eicosanoid generating capacities of different tissues from the rainbow trout,
      Oncorhynchus mykiss.
AB  - The eicosanoid generating potential of the brain, gills, skin, ovary, muscle,
      eye, liver, spleen, heart, and alimentary canal in the rainbow trout,
      Oncorhynchus mykiss, was examined. All the organs/tissues examined synthesized
      the 12-lipoxygenase products, 12-hydroxyeicosatetraenoic acid (12-HETE), and 12
      hydroxyeicosapentaenoic acid (12-HEPE), implying the widespread nature of this
      enzyme in trout. Both prostaglandin E and LTC were also found in variable amounts
      in the organs, with the greatest amount of PGE found in the gill. Leukotriene
      (LT) B4 and LTB5 were found in supernatants from calcium ionophore-challenged
      brain, skin, ovary, liver, spleen, and heart, but the lipoxins A4 and A5 were
      only present in brain, ovary, and spleen in relatively small amounts. As lipoxins
      have previously been shown to be synthesized by macrophages in rainbow trout
      [Pettitt et al., J. Biol. Chem. 266, 8720-8726 (1991)], and related cells
      (microglial cells) are found in the brain of mammals, the localization of
      macrophage-like cells in trout brain was investigated immunocytochemically.
      Monoclonal antibodies specific for trout leucocytes failed to identify any
      microglial-like cells in sections of the brain, although microvessels containing
      immuno-positive reaction products were observed. A number of distinct
      lipoxygenase products were found in supernatants of ionophore-challenged gill,
      including 14-hydroxydocosahexaenoic acid, 12-HETE, and 12-HEPE, and a large
      number of dihydroxy fatty acid derivatives with conjugated triene chromophores.
      One of these products was tentatively identified as 8(R),15(S)
      dihydroxyeicosatetraenoic acid, a dual 12- and 15-lipoxygenase product, but
      apparently no LTB4 was generated by this tissue.

PMID- 7637571
TI  - Combinatorial expression of immediate early genes in single neurons.
AB  - To address the question how relatively small numbers of immediate early gene
      (IEG) could specifically couple a wide range of stimulus-response cascades, we
      examined the possibility that IEG could be expressed heterogeneously in
      individual neurons. Analysis of multiple IEG in single neurons revealed that many
      individual DRG neurons express several IEGs. The combinatorial expression of IEGs
      by individual DRG displays substantial heterogeneity. Analysis of mRNA species
      encoding AP-1 composition in single cells also revealed coordinated change of
      mRNAs coding for AP-1 factors after membrane depolarization. Our results indicate
      that differential expression of IEG in individual cells, and the possible
      interaction among them may represent a mechanism by which the specificity in
      stimulation-response coupling may be achieved by IEGs.

PMID- 7637570
TI  - Cholinergic regulation of tachykinin- and enkephalin-gene expression in the rat
      striatum.
AB  - Ninety-five percent of the neurons in the corpus striatum of the rat are medium
      spiny projection neurons, which contain tachykinins such as substance P,
      neurokinin A, and neurokinin B and the opiate peptides, enkephalin and dynorphin.
      The remaining 5% consist of interneurons, of which a small but significant
      proportion are cholinergic. The influence of these cholinergic interneurons on
      the neuropeptidergic projection systems in the striatum is poorly understood at
      this time. The present study explores the relationship between cholinergic
      receptor activation or muscarinic blockade on striatal neuropeptide gene
      expression. Adult male Sprague-Dawley rats were treated chronically either with a
      cholinergic agonist (physostigmine: 0.5 mg/kg/3 x day), a muscarinic antagonist
      (scopolamine HCl: 0.4 mg/kg/3 x day), or vehicle (PBS: 0.1 ml/100 g) administered
      for 6 days (s.c.). In situ hybridization was performed with probes directed
      against mRNAs for beta-preprotachykinin (a transcript containing substance P,
      neurokinin A, and other tachykinins), neurokinin B and preproenkephalin.
      Physostigmine administration resulted in a 12% decrease in the dorsolateral
      caudate-putamen and a 27% increase in the core of the nucleus accumbens in
      substance P/neurokinin A mRNA; and a 29% increase in the caudate-putamen and an
      11% increase in the core of the nucleus accumbens in preproenkephalin mRNA
      levels. Scopolamine treatment resulted in a 28% and 48% decrease, respectively,
      in the caudate-putamen and in the shell of the nucleus accumbens in substance
      P/neurokinin A mRNA levels. Neurokinin B mRNA levels were increased by 50% in the
      shell of the accumbens after scopolamine. Preproenkephalin mRNA levels increased
      by 24% in the caudate-putamen and decreased by 20% in the core of the nucleus
      accumbens. From these results we tentatively conclude that cholinoceptive
      neuropeptidergic neurons are segregated along dorsoventral and mediolateral axes
      in the striatum, thus giving rise to non-homogenous responses upon cholinergic
      receptor activation or muscarinic blockade.

PMID- 7637569
TI  - Dietary manipulation of long-chain polyunsaturated fatty acids in the retina and
      brain of guinea pigs.
AB  - High levels of n-6 docosapentaenoic acid (22:5n-6) have been reported in the
      retina of guinea pigs fed commercially-prepared gain-based rations (commercial
      diet). In rats and monkeys, high levels of 22:5n-6 are an indicator of n-3
      polyunsaturated fatty acid (PUFA) deficiency. We have examined the fatty acid
      composition of the retina and brain in guinea pigs fed a commercial diet or one
      of three semi-purified diets containing three different levels of n-3 PUFA. The
      diets comprised a diet deficient in n-3 PUFA (semi-purified diet containing
      safflower oil), two diets containing alpha-linolenic acid (standard commercial
      laboratory diet and semi-purified diet containing canola oil), and a diet
      containing alpha-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid
      (DHA) (semi-purified diet containing canola oil, safflower oil, and fish oil).
      Two groups of guinea pigs were given the diets from day 1 to 4 wk or day 1 to 8
      wk, when they were sacrificed and the retinal tissues were extracted and analyzed
      for PUFA content by gas-liquid chromatography. Fatty acid analyses of the retinal
      phospholipids of the four-week-old animals revealed that the group fed DHA (from
      the fish oil) had the highest level of DHA (32%), compared with values of 19 and
      13% for the groups fed canola oil diet and commercial diet, respectively, and 2%
      for the group fed the diet deficient in n-3 PUFA.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7637572
TI  - Transcriptional and post-transcriptional mechanisms regulating neurofilament and
      tubulin gene expression during normal development of the rat brain.
AB  - The transcription of the beta II-, beta IV- and alpha 1-tubulin genes as well as
      that of the three neurofilament genes, NF-L, NF-M and NF-H, was examined during
      the course of postnatal brain development. Changes in the transcriptional
      activity of these genes were studied using run-off transcription assays with
      nuclei isolated from the rat cerebral cortex at postnatal days P2, P5, P10 and
      adult stages. Northern blotting of total RNA isolated from the cerebral cortex
      was used to compare changes in steady-state mRNA levels with transcriptional
      changes that occurred in the cerebral cortex during the postnatal interval.
      Nuclear run-off assays showed that beta II- and alpha 1-tubulin gene
      transcription rates were maximal from P2-P5 and declined at later times. Changes
      in the steady-state mRNA levels for these two genes followed the same general
      pattern as transcription, but in the case of beta II-tubulin mRNA, were more
      dramatic. beta IV-tubulin gene transcription dropped between P2 and P5 and then
      increased progressively to the adult stage, coordinate with an increase in beta
      IV-tubulin steady-state mRNA levels. NF-L and NF-H genes showed similar patterns
      of transcriptional change during the postnatal interval, with maximal rates of
      transcription at P5 followed by a decline at later times. The steady-state levels
      of NF-L and NF-H mRNAs changed in a manner opposite to that of transcription and
      increased progressively during the postnatal interval. This suggests that mRNA
      stabilization is the main factor regulating the steady-state levels of NF-L and
      NF-H mRNAs in postnatal brain. For the NF-M gene, the developmental transcription
      pattern was also dissociated from steady-state mRNA level changes, but differed
      from the transcription patterns of the NF-L and NF-H genes. This suggests the
      importance of post-transcriptional mechanisms in regulating NF-M mRNA levels in
      brain and also indicates that some differences exist in the regulatory mechanisms
      which control NF-M compared to NF-L and NF-H mRNA levels.

PMID- 7637574
TI  - Localization of fibroblast growth factor-9 mRNA in the rat brain.
AB  - We examined the localization of fibroblast growth factor-9 (FGF-9) mRNA in the
      rat brain by in situ hybridization. FGF-9 mRNA was moderately or weakly expressed
      in widespread regions including the olfactory bulb, caudate putamen, cerebral
      cortex, hippocampus, thalamus, hypothalamus, midbrain, brainstem and cerebellum.
      However, FGF-9 mRNA was also strongly expressed in several specific nuclei
      including the red nucleus and oculomotor nucleus in the midbrain, the vestibular
      nucleus and facial nucleus in the brainstem and the medial cerebellar nucleus,
      interposed cerebellar nucleus and lateral cerebellar nucleus in the cerebellum.
      The cellular localization of FGF-9 mRNA indicated that the mRNA in the rat brain
      was expressed preferentially in neurons, although FGF-9 was originally isolated
      from human glioma cells. The localization profile of FGF-9 mRNA is different from
      those of aFGF, bFGF and FGF-5 mRNAs reported previously. The present findings
      indicate that FGF-9 has a unique role in the brain.

PMID- 7637573
TI  - Dopaminergic control of gene transcription during striatal ontogeny: c-fos
      induction by D1 receptor activation in the developing striosomes.
AB  - During striatal development, dopamine afferents initially reach the striosomal
      compartment, and this early dopamine innervation is thought to influence, through
      the D1 receptors first expressed in the developing patches, the phenotype of
      target striatal cells. Dopaminergic control of gene expression during ontogeny
      could be mediated by transcription factors such as c-fos, whose expression is
      regulated by synaptic signals. However, in the striatum of intact adult animals,
      D1 dopamine agonists fail to induce c-fos expression. The c-fos response to D1
      receptor activation in adults requires a previous sensitization of dopaminergic
      receptors by chronic treatment with reserpine or by lesion of the nigro-striatal
      pathway. In this work, we investigated through in situ hybridization the ability
      of striatal cells to express c-fos messenger RNA (mRNA) in response to the D1
      agonist SKF 38393 (4 to 8 mg/kg) in developing mice. During a transient postnatal
      period, c-fos expression in a patchy distribution was induced by D1 receptor
      activation: only a faint response was detected on postnatal day 1, but islands of
      strong hybridization signals for c-fos mRNA in response to the D1 agonist were
      observed at postnatal day 3, with a progressive decrease in intensity from day 6
      to day 15. The distribution of this transient c-fos response corresponded to the
      early striosomal compartment since it matched with the regions of intense mu
      opioid and dopamine-D1 receptor binding, as assessed by autoradiography performed
      on adjacent sections. By day 21, as in adult animals, no more c-fos response to
      D1 agonists was observed, except in the most caudal division of the striatum.
      Strong expression, which persisted into adulthood, was detected in this region
      from the third postnatal day. This induction of striatal c-fos expression by D1
      agonists during early postnatal development is indicative of an enhanced
      sensitivity of D1 receptors or of D1-associated transduction pathways compared to
      the adult pattern, and suggests a possible role for dopamine-controlled c-fos
      gene expression in the development of target striatal neurons during this
      critical period.

PMID- 7637575
TI  - Molecular characterization and differential mRNA tissue distribution of mouse
      apolipoprotein D.
AB  - The mouse apolipoprotein D gene was isolated from a brain cDNA library. The
      nucleotide sequence contains a unique reading frame coding for a protein sharing
      79.5% homology with human apoD, 86.2% homology with rabbit apoD and 92.6%
      homology with rat apoD. The four sequences have two potential asparagine-linked
      glycosylation sites at residues 45 and 78, and possess the two consensus
      sequences of the lipocalin family which coincide with the most conserved regions
      in the four species studied. The distribution of apoD mRNA among mouse organs was
      determined by Northern blot and quantitative dot blot analysis. The highest
      levels of mRNA were found in the central nervous system (CNS), namely in the
      spinal cord, the cerebellum and the brain. Very low concentrations were detected
      in all the other organs tested. In some organs (spleen, kidney, intestines,
      heart), a second messenger of lower molecular weight was detected. Gene
      expression was also measured in rat tissues. As in the mouse, rat CNS was found
      to be by far the highest expressor of apoD mRNA, in contrast to the rabbit and
      human. Levels of expression in most mouse and rat organs appeared to be much
      lower than in the same organs of the rabbit and human. Since apoD is expressed at
      sites of nerve regeneration as well as apoE, our results raise the question of
      whether or not the two proteins play a coordinated role in the CNS.

PMID- 7637576
TI  - A novel glial fibrillary acidic protein mRNA lacking exon 1.
AB  - Glial fibrillary acidic protein (GFAP) is the major intermediate filament protein
      in the mature astrocytes. We have assayed for the presence of GFAP mRNA gene in
      mouse tissues outside the nervous system. Nuclease S1 protection experiments show
      that RNAs lacking exon 1 are transcribed in bone marrow. From a mouse bone marrow
      cDNA library we isolated GFAP cDNAs which start in the 3' part of intron 1 and
      contain all the downstream GFAP exons. The new GFAP mRNAs, which we call GFAP
      gamma mRNAs, are already present in the brain at embryonic day 15 and in adult
      forebrain and cerebellum. Their presence in astrocytic cell lines suggests that
      astrocytes may be the site of in vivo expression of these mRNAs. In addition we
      have detected GFAP gamma mRNAs in mouse spleen. Furthermore in human an analogous
      GFAP mRNA containing the 3' part of intron 1 and lacking the exon 1 is also
      present in adult brain. These results suggest a new regulation of the GFAP gene
      expression.

PMID- 7637577
TI  - Altered IGFBP5 gene expression in the cerebellar external germinal layer of
      weaver mutant mice.
AB  - The IGF system components play important roles in cerebellar development as
      demonstrated by their specific spatial-temporal expression. IGF-I, type I IGF
      receptor (IGFR-I), IGFBP2 and IGFBP5 mRNA are localized in distinct cell
      populations, and all are expressed at the highest levels at the peak of Purkinje
      cell growth, active synaptogenesis and dendritic formation. To understand IGF-I's
      action at the cellular level, in situ hybridization was employed to investigate
      the distribution of IGF system gene transcripts in the cerebellum of weaver
      mutant mice (wv/wv). Although located ectopically, the surviving Purkinje cells
      express IGF-I mRNA at the same level in wv/wv as in +/+. No alteration in the
      cellular distribution or mRNA levels was observed with IGFBP2, or IGFR-I mRNAs.
      However, the pattern of IGFBP5 expression is altered in the external germinal
      layer of wv/wv mice. Not only is IGFBP5 expressed by more granule cell precursors
      of wv/wv cerebellum, but its mRNA level is 2.3 fold that of +/+. The altered
      IGFBP5 gene expression in granule cell precursors may modulate the interaction of
      IGF-I with IGFR-I in ways that contribute to their massive death occurring in the
      development of wv/wv cerebellum.

PMID- 7637578
TI  - Neuroblastoma Neuro2A cells stably expressing a cloned mu-opioid receptor: a
      specific cellular model to study acute and chronic effects of morphine.
AB  - Several cellular systems display desensitization and downregulation of opioid
      receptors upon chronic treatment, suggesting that they could be used as a model
      system to understand opioid tolerance/dependence. However, a model system
      containing a homogeneous population of mu-opioid receptors, the receptors at
      which morphine and related opioids act, has been lacking. To approach this
      problem, the mu-opioid receptor (MOR-1) was stably expressed in murine
      neuroblastoma Neuro2A cells after transfection. The expressed receptor was
      negatively coupled to adenylyl cyclase through Gi/Go proteins, displayed high
      affinity ligand binding, and was expressed in high number (2.06 pmol/mg of
      [3H]diprenorphine binding sites). In addition, loss of ability of mu-opioids to
      acutely inhibit forskolin-stimulated cAMP formation was observed after 4-24 h of
      chronic exposure to these agonists with concentrations as low as 300-500 nM. The
      effects of chronic morphine or [D-Ala2,N-MePhe4,Gly-ol]enkephalin (DAMGO)
      administration were found to be time- and concentration-dependent. Cross
      'tolerance' was also observed. Thus the IC50 value of DAMGO to inhibit adenylyl
      cyclase was increased by 27-fold from 4.3 nM in control cells to 117 nM in cells
      pretreated with 300 nM morphine; there was no effect on the inhibition of
      adenylyl cyclase mediated by muscarinic receptors. Further, receptor
      downregulation accompanied the desensitization process. However, different time
      dependence for these two processes suggests, in line with other studies, that
      these are entirely different cellular adaptation processes. In addition, the
      opioid antagonist naloxone induced an acute increase in intracellular cAMP level
      (2-3 times above the control level) following chronic agonist exposure. This
      process was also concentration-dependent. Overall, these results suggest that the
      cell line utilized in this study has a homogeneous population of mu-opioid
      receptors, providing an ideal cellular model to study the molecular mechanisms
      underlying chronic morphine treatment.

PMID- 7637579
TI  - A key enzyme in the biosynthesis of neurosteroids, 3 beta-hydroxysteroid
      dehydrogenase/delta 5-delta 4-isomerase (3 beta-HSD), is expressed in rat brain.
AB  - In rat brain, the presence of pregnenolone and progesterone, not attributable to
      peripheral glandular sources, has been demonstrated and thus the two compounds
      can be classified as neurosteroids. In vitro experiments have shown the
      conversion of pregnenolone, a 3 beta-hydroxy-delta 5-ene steroid, into
      progesterone, a delta 4-oxo steroid, thus demonstrating a 3 beta-hydroxysteroid
      dehydrogenase/delta 5-delta 4 isomerase (3 beta-HSD) enzymatic activity. The
      conversion of 3 beta-hydroxy-delta 5-derivatives into the corresponding delta 4
      oxo steroids by 3 beta-HSD is an essential step in the biosynthesis of all
      steroid hormones in endocrine glands. To date, four isoforms of 3 beta-HSD have
      been characterized in the rat. We report here the selective expression of a 3
      beta-HSD isoform in rat brain. An in situ hybridization study, using an
      oligonucleotide common to the 4 known isoforms, demonstrated 3 beta-HSD mRNA in
      neurons of the olfactory bulb, striatum, cortex, thalamus, hypothalamus, septum,
      habenula, hippocampus and cerebellum. The cerebellum showed the highest level of
      3 beta-HSD mRNA corresponding to a transcript of 1.8 kb. Nucleotide sequencing of
      PCR-amplified cDNA fragments from cerebellar mRNA indicated the expression of an
      isoform of 3 beta-HSD cDNA very closely related to the isoform I expressed in the
      adrenals and gonads. Further evidence for the expression of 3 beta-HSD gene in
      the brain was demonstrated utilizing anti-peptide 3 beta-HSD antibodies which
      revealed an immunoreactive protein of approximately 45 kDa in the cerebellum. Our
      results demonstrate for the first time the expression of the enzyme 3 beta-HSD in
      the brain, at both the mRNA and protein levels. Since several neuroactive
      neurosteroids are substrates or products of the 3 beta-HSD enzymatic activity,
      our findings offer new possibilities to study the regulatory mechanisms governing
      their biosynthesis in the brain.

PMID- 7637580
TI  - Molecular cloning of cDNA encoding a bovine selenoprotein P-like protein
      containing 12 selenocysteines and a (His-Pro) rich domain insertion, and its
      regional expression.
AB  - When cDNA containing proteins enriched in the bovine cerebellar cortex were
      cloned, a clone which seemed to encode a selenoprotein P-like protein was
      isolated. The coding nucleotide sequence of its cDNA insert displayed high
      homology to rat and human selenoprotein P cDNA but contained 12 rather than 10
      TGAs (12 rather than 10 selenocysteines in deduced amino acids), a tandem repeat
      of one CACTCC (His-Ser) and seven CATCCCs (His-Pro), and a 3' untranslated region
      approximately 890 bases shorter than that of rat liver selenoprotein P. RT-PCR
      using a set of primers flanking to the repeat displayed the existence of mRNA
      without the repeat. The tandem repeat and its adjacent region consisted of a
      similar motif of CAC/TCC/AC/T. Thus, these proteins included a (His-Pro) rich
      domain with a slightly negative free energy change irrespective of having the
      tandem repeat or not. Such His-Pro repeats reportedly exist in the segmentation
      gene paired or homeobox protein Om(1D) of Drosophila. Moreover, both this
      selenoprotein P-like protein mRNA and selenoprotein P mRNA were expressed in all
      the areas of the brain but most prominently in the cerebellar cortex,
      hippocampus, and olfactory bulb. These findings suggest the possibility that
      these selenoproteins are major selenium carriers in the brain and play a role in
      the morphological response of nerve or glial cells.

PMID- 7637581
TI  - Id gene expression during development and molecular cloning of the human Id-1
      gene.
AB  - Id genes encode helix-loop-helix proteins that inhibit transcription by forming
      inactive heterodimers with basic helix-loop-helix (bHLH) proteins. bHLH proteins
      normally form either homodimers or heterodimers with other bHLH proteins and bind
      to a DNA sequence element activating transcription. Id-containing heterodimers
      are inactive because Id proteins lack the basic amino acid region necessary to
      form a DNA-binding domain. We have examined the relative levels of Id-1 and Id-2
      mRNA during normal development and in malignant tissues. In the course of these
      experiments we cloned and sequenced the human Id-1 cDNA. Two related cDNA
      molecules encoding human Id-1 mRNAs were identified. Id-1a is a cDNA of 958
      nucleotides and can encode a protein of 135 amino acids. Id-1b cDNA is 1145
      nucleotides, can encode a protein of 149 amino acids, and appears to be a splice
      variant of Id-1a. The amino acid sequence of human Id-1 is greater than 90%
      homologous to that of mouse Id-1. The patterns of Id-1 and Id-2 expression during
      mouse development vary widely, and we detected Id-1 expression in human fetal and
      adult tissues from lung, liver, and brain. High Id-1 mRNA expression was found in
      many human tumor cell lines, including those isolated from nervous system tumors.
      We mapped Id-2 to human chromosome 2p25.

PMID- 7637582
TI  - Human and mouse dopamine transporter genes: conservation of 5'-flanking sequence
      elements and gene structures.
AB  - Synaptic reaccumulation of the neurotransmitter dopamine is mediated by the
      dopamine transporter (DAT), a member of the family of twelve transmembrane
      domain, sodium- and chloride-dependent neurotransmitter transporters. Several DAT
      features, including its exclusive expression in dopaminergic neurons, implication
      in cocaine action, and prominent role in the mechanisms of Parkinsonism-inducing
      neurotoxins, make understanding of the DAT gene of interest. Isolation and
      characterization of the human and mouse DAT genes has allowed elucidation of
      similarities between each and other members of this transporter gene family.
      Sequences 5' to transcriptional start sites contain G-C rich, TATA-less, CAAT
      less regions with striking conservation between human and mouse gene flanking
      regions. These studies suggest sequence elements that are candidates to
      contribute to the dopamine transporter's dopaminergic cell-specific expression.

PMID- 7637583
TI  - The human D1A dopamine receptor gene promoter directs expression of a reporter
      gene to the central nervous system in transgenic mice.
AB  - Dopamine receptors are involved in many aspects of dopaminergic neurotransmission
      including regulation of motor control, cognition, affect and neuroendocrine
      function. The D1A receptor is the most widely distributed dopamine receptor in
      the brain and is expressed at high levels in the striatum and nucleus accumbens,
      but is also found throughout cortical, limbic, hypothalamic and thalamic brain
      regions. We have cloned a 6.4 kb fragment 5' of the human D1A dopamine receptor
      gene and shown that this region activates transcription of the chloramphenicol
      acetyltransferase (CAT) gene in a cell-specific manner. To study the expression
      of these sequences in vivo we analyzed the expression of the E. coli lac Z gene
      under the regulation of the 6.4 kb fragment in transgenic mice. Expression of the
      transgene was primarily detected in the brain, with only low levels detected in
      peripheral tissues. The 5' flanking sequences were able to direct the tissue
      specific expression of lac Z in three different lines of transgenic mice, to a
      number of brain regions including the caudate-putamen, thalamus, amygdala,
      cerebral cortex, hippocampus and hypothalamus. Greatest expression of the lac Z
      gene was detected in areas of the thalamus and amygdaloid complex. In the
      striatum, beta-galactosidase activity was restricted to neurons within the matrix
      and was not detected within striosomes. Results of this study demonstrate that
      the 6.4 kb region upstream of the human D1A receptor gene is sufficient to confer
      tissue-specific expression in the CNS of transgenic mice. Furthermore, expression
      of the transgene to neurons within the matrix of the striatum, but not the
      striosomes suggests that expression of the D1A receptor may be regulated
      differently within these areas.

PMID- 7637584
TI  - Chronic ethanol treatment upregulates the NMDA receptor function and binding in
      mammalian cortical neurons.
AB  - In the present study, we investigated the effects of chronic ethanol exposure on
      NMDA-mediated increase in intracellular calcium concentration ([Ca2+]i) by means
      of fluorescent measurement of [Ca2+]i with Fura-2AM in mammalian cortical
      cultured neurons, and the radioligand [3H]MK-801 binding to cortical neuronal
      membranes. Chronic exposure of the cortical neurons to ethanol (50 mM, 5 days)
      did not produce any change in the cell protein, morphological appearance, and the
      resting [Ca2+]i; however, it significantly enhanced the NMDA-mediated increase in
      [Ca2+]i. The EC50 value of NMDA was not significantly altered following chronic
      ethanol exposure, however, its Emax value was increased by approximately 45%.
      Furthermore, chronic ethanol exposure increased the specific [3H]MK-801 binding
      in cortical neuronal membrane preparation by approximately 30%. The enhancement
      of the NMDA-mediated increase in [Ca2+]i and the increase in [3H]MK-801 specific
      binding were reversed following 48 h ethanol withdrawal. Additionally, this
      enhanced NMDA response and the increased [3H]MK-801 specific binding were
      susceptible to blockade by the concomitant chronic exposure of the cortical
      neurons to the NMDA receptor competitive (20 microM CPP), and non-competitive (1
      microM MK-801) antagonists, but not by the non-NMDA receptor antagonist, CNQX (10
      microM), and the L-type calcium channel blocker, nitrendipine (10 microM). Taken
      together, these results suggest that chronic ethanol exposure upregulated the
      NMDA receptor function and binding in cortical cultured neurons, and this
      increased NMDA receptor function is a NMDA receptor-mediated process. This
      altered NMDA receptor function may be responsible for the chronic ethanol-induced
      behavioral consequences and withdrawal syndrome associated with chronic ethanol
      exposure.

PMID- 7637585
TI  - Na+ channel beta 1 subunit mRNA: differential expression in rat spinal sensory
      neurons.
AB  - The brain Na+ channel beta 1 subunit (Na beta 1) mRNA has recently been localized
      within rat central nervous system where it is expressed at differing levels in
      different types of neurons. In the present study, we have studied the expression
      pattern of Na beta 1 mRNA in rat dorsal root ganglion (DRG) neurons using non
      radioactive in situ hybridization histochemistry. Na beta 1 mRNA is
      differentially expressed in adult DRG, with higher levels in intermediate-to
      large (> approximately 25 microns in diameter) DRG neurons than in small (< 25
      microns) DRG neurons. This cell body size-related Na beta 1 mRNA expression is
      consistently observed beginning at postnatal day 4 and continues throughout
      development to adulthood. The present results indicate that (i) Na beta 1 mRNA is
      expressed in neurons in the peripheral nervous system and (ii) Na beta 1 gene
      expression is differentially regulated in DRG neurons in relation to their cell
      body sizes.

PMID- 7637586
TI  - Calbindin D28k mRNA in hippocampus, superior temporal gyrus and cerebellum:
      comparison between control and Alzheimer disease subjects.
AB  - To further investigate the role of calbindin D28k in Alzheimer's disease (AD);
      hippocampus, superior temporal gyrus and cerebellum from control and AD cases
      were examined by quantitative in situ hybridization. We report here a decrease in
      CaBD28k mRNA in the CA2 region of AD hippocampus compared to control subjects.
      There were no significant differences between AD and control subjects in the
      other regions studied.

PMID- 7637587
TI  - Analysis of the decremental nature of LTP in the dentate gyrus.
AB  - The persistence of long-term potentiation (LTP) in the dentate gyrus was compared
      for two tetanization protocols: 50 trains on one day, or 50 trains on 5
      consecutive days. LTP induction was significantly greater in the 250 train
      condition, but the LTP decay rate over weeks was similar between conditions. The
      decay of LTP could not be accounted for by deterioration of the preparation.
      Successive days of stimulation caused repetitive induction of immediate early
      genes, but did not prolong LTP, suggesting that either the effects of gene
      expression on LTP stabilization had saturated, or that these genes play other
      roles in synaptic plasticity.

PMID- 7637588
TI  - Colchicine induces the GAP-43 gene expression in rat hypothalamus.
AB  - Injection of colchicine, a mitogen inhibitor, in the dorsal third ventricle
      induced the expression of the growth associated protein-43 (GAP-43) mRNA in some
      groups of cells of the adult rat brain. These mRNAs were detected by in situ
      hybridization histochemistry using an alkaline phosphatase labeled
      oligonucleotide probe. A substantial up-regulation of GAP-43 mRNA was noticed by
      the increase of both the number of positive cells and the intensity of the
      hybridization signal. These changes were observed in the hypothalamic nuclei
      located near the ventral third ventricle, namely the preoptic area, the
      supraoptic nucleus, the peri- and the paraventricular nuclei of the hypothalamus,
      the dorsal subnucleus of the ventromedial nucleus, the arcuate nucleus and the
      posterior part of the peri-mammillary region. Such abundant GAP-43 mRNA positive
      cells have not been observed in control adult rat hypothalamus. Since the
      positive cell number and shape initially suggested that these were neurons or
      astrocytes, double labeling in situ hybridization using both radioactive (for the
      detection of GFAP mRNA as a marker of astrocyte) and non-radioactive (for the
      detection of GAP-43 mRNA) probes was carried out. This demonstrated that these
      GAP-43 mRNA positive cells were not astrocytes. In addition enhanced GAP-43 mRNA
      expression was also found in some neuronal component, particularly in
      neurosecretory magnocells of the pareaventricular and the supraoptic nuclei. This
      up-regulation was further confirmed by the Northern blot analysis. About five
      fold increase in GAP-43 mRNA in the colchicine-treated hypothalamic tissue was
      shown.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7637589
TI  - Exon 2 of the gene for neural cell adhesion molecule L1 is alternatively spliced
      in B cells.
AB  - L1CAM is a neural cell adhesion molecule expressed mainly on neurones' cell
      surface and plays an important role in the developing fetal brain. Recently, we
      have shown that mutations in the gene encoding L1CAM are responsible for three
      related neurological disorders including the most common form of inherited
      hydrocephalus. During our genetic analysis, we have discovered that L1CAM is also
      expressed on the surface of B cells but that the messenger RNA in this tissue is
      different to that in brain through alternative splicing of the L1 gene. This
      indicates that this region of the L1 molecule has a distinct role in brain cells
      compared to B lymphocytes and confirms its importance in brain development.

PMID- 7637590
TI  - Sequence homology of rat and human HCNP precursor proteins, bovine
      phosphatidylethanolamine-binding protein and rat 23-kDa protein associated with
      the opioid-binding protein.
AB  - The hippocampal cholinergic neurostimulating peptide (HCNP) enhances
      acetylcholine synthesis in rat medial septal tissues. We have cloned the cDNAs of
      the precursor proteins of rat and human HCNP and deduced their respective amino
      acid sequences. The HCNP sequences aligned at the N-terminal regions of their
      precursors. The deduced amino acid sequences showed homology with those of the
      bovine brain phosphatidylethanolamine-binding protein and the rat protein
      associated with the opioid-binding protein. These observations suggest that the
      HCNP precursor proteins may have multiple functions.

PMID- 7637591
TI  - New variant prion protein in a Japanese family with Gerstmann-Straussler
      syndrome.
AB  - We found novel variants in the open reading frame of the prion protein (PrP) gene
      in a family with Gerstmann-Straussler syndrome (GSS). Codon 219Lys variant is a
      normal polymorphism which we found recently. Some GSS cases were identified with
      codon 102 mutation (proline to leucine) and codon 219Lys polymorphism. While two
      families had a codon 102 mutation and codon 219Lys polymorphism in different
      alleles, 4 patients in one family had both in the same allele. The
      clinicopathological features of these 4 patients were clearly different from
      previously reported GSS patients with codon 102 mutation. These cases should be
      reported as a new variant of GSS.

PMID- 7637593
TI  - Prolonged expression of Fos-related antigens, Jun B and TrkB in dopamine
      denervated striatal neurons.
AB  - Previous studies have demonstrated that striatal dopamine-denervation leads to a
      long-term increase in Fos-related antigen(s) (FRA's) in striatal neurons. Because
      Fos-family proteins bind to DNA by dimerizing to Jun-family proteins we
      investigated the expression of Jun B protein 2 weeks and 1 month after striatal
      dopamine-denervation, produced by medial forebrain bundle transection. We also
      investigated the effects of this lesion on TrkB-immunoreactivity in the striatum.
      FRA's (as previously reported) and Jun B were expressed in striatal neurons
      following dopamine-denervation, and in addition, there was an increase in
      expression of TrkB in the striatum on the dopamine-denervated side. These results
      show that striatal dopamine depletion leads to a long-term up-regulation of FRA's
      and Jun B in the striatum, and this may be related to other biochemical changes
      previously reported to occur in striatal neurons (e.g.: D2-dopamine receptor up
      regulation) after dopamine depletion. In addition, FRA and Jun B expression may
      induce increased production of TrkB after dopamine-denervation.

PMID- 7637594
TI  - [Emergency intra-osseous rehydration in children during a cholera epidemic].

PMID- 7637592
TI  - Acute administration of alpha-methyl-para-tyrosine alters levels of
      norepinephrine transporter mRNA in the rat brainstem.
AB  - This study investigated whether rat norepinephrine transporter (NET) mRNA levels
      would be altered by alpha-methyl-p-tyrosine (alpha-MPT), a tyrosine hydroxylase
      inhibitor. While NE levels decreased at 1 and 3 days but recovered at 7 days
      after alpha-MPT, NET mRNA levels decreased at 3 and 7 days but not at 1 day after
      alpha-MPT. The results indicate that acute treatment with alpha-MPT led to a
      delayed time response in its effects on NET mRNA and NE levels in the rat brain.

PMID- 7637596
TI  - [Lymphatic filariasis: towards a better use of diethylcarbamazine].

PMID- 7637595
TI  - [Should travelers to Vietnam be vaccinated against japanese encephalitis?].

PMID- 7637597
TI  - [Creation of a blood bank at the GRALL pediatric hospital in Ho Chi Minh,
      Vietnam].

PMID- 7637598
TI  - [Antimalarial prophylaxis in Cambodia: experience of a French contingent of
      APRONUC].

PMID- 7637599
TI  - [Anemia and nutritional status in young children in northern Togo].

PMID- 7637600
TI  - [Fulminant hepatitis during antitubercular drug treatment. Two cases].

PMID- 7637601
TI  - [Can bilharziasis be considered a health priority in western Africa, justifying
      control programs of large scope?].

PMID- 7637602
TI  - [HTLV-I and HTLV-II viruses: fifteen years after their description].

PMID- 7637603
TI  - [Cambodia: the undermining by AIDS or the difficult rebuilding of a destroyed
      country].

PMID- 7637604
TI  - [Management of an epidemic].

PMID- 7637605
TI  - [Military service medicine and tropical medicine].

PMID- 7637606
TI  - [Southeast Asia: a recapture?].

PMID- 7637607
TI  - [Clinical and therapeutic aspects of hepatic amebiasis in Cambodia].
AB  - Amoebic liver abscess is a common disease in developing countries. Although
      therapy is now perfectly standardized, errors and inaccuracies are frequent in
      daily practice. A study was performed at the Calmette Hospital in Phnom Penh
      (Cambodia) to evaluate and improve this situation. Diagnostic criteria and the
      outcome of treatment with oral or parenteral metronidazole were analyzed in 38
      patients presenting amoebic liver abscess. Hepatalgia was observed in 100% of
      cases. Hyperleukocytosis and enhancement of the sedimentation rate occurred in
      95% of cases. Diagnosis was confirmed by ultrasonography. Serodiagnosis, given
      its high cost, was not indispensable. Metronidazole was of comparable
      effectiveness and tolerance (90%) whether administered by the oral or parenteral
      route. The parenteral route should be used only for patents presenting digestive
      intolerance. Drainage of the abscess is necessary in cases characterized by
      immediate complications, abscesses with diameters greater than 120 mm and absence
      of improvement after 5 days of treatment.

PMID- 7637608
TI  - [Septic meningitis in children in Rwanda from 1983 to 1990. Retrospective study
      at the Kigali Hospital Center].
AB  - To assess septic meningitis in pediatric units in terms of the bacteriologic
      distribution, mortality, and groups at risk, we conducted a retrospective study
      in the pediatric department of the Kigali Hospital Center (Rwanda). Based on
      bacteriologic study of 1215 cerebrospinal fluid samples, there were 321 cases of
      septic meningitis due to identifiable germs and 68 involving cloudy fluid with no
      detectable germs, i.e. 1.5% of admissions to the Pediatric Unit of the Kigali
      Hospital Center. The most common organisms were pneumococcus (36.5%), Haemophilus
      influenzae (31%), salmonella (13%), and meningococcus (11.5%). Most of the
      children (75%) presenting septic meningitis were under the age of 5 years.
      Overall mortality was 38% with rates of 52% and 39% for cases involving
      pneumococcus and salmonella respectively. The predominant clinical symptoms of
      pneumococcus meningitis were coma (p:0.000055) and respiratory compromise
      (p:0.02). In contrast Haemophilus influenzae meningitis was associated with a
      lower incidence of coma (p:0.05) and malnutrition (p:0.017). Salmonella
      meningitis was characterized by a higher incidence of fever over 38.9 degrees C
      (p:0.025) and malnutrition (p:0.01). In patients with meningococcus meningitis,
      the incidence of convulsions appeared to be higher, at the threshold of
      statistical significance (p:0.052), whereas coma (p:0062) and respiratory
      distress (p:0.0024) were uncommon. Independently of etiology, no clinical symptom
      was associated with a statistically higher risk for death.

PMID- 7637609
TI  - [Health personnel and population practices in the diagnosis of malaria and use of
      antimalarial drugs in Dakar].
AB  - The practices of health care workers and the population with regard to diagnosis
      of malaria and use of antimalarial drugs were studied in the city of Dakar from
      September 1991 to March 1992. Study included 847 heads of family, 191 treatment
      prescribers including 77 physicians, 53 nurses and 61 midwives, and 60
      pharmacists. Three separate questionnaires were used: one for the population, one
      for physicians and paramedical staff, and one for pharmacists. The data collected
      showed that the 4 main symptoms used by both health care workers and the general
      population for diagnosis of malaria were fever, chills, vomiting, and headache.
      Treatment was administered upon suspicion of infection by 72% of treatment
      prescribers. Chloroquine was the drug most widely used by prescribers and for
      self-treatment of malaria. Prophylactic drug treatment was practised by all
      groups studied except treatment prescribers but was unappropriate for the target
      groups. Chloroquine is the drug most widely used to protect against the disease.
      Pharmacists have adequate supplies but distribution is poor. Despite promising
      results in the fight against malaria, further effort is needed to train health
      care workers and provide information to the population.

PMID- 7637610
TI  - [Problems after thyroid gland surgery in Burkina Faso, 83 cases].
AB  - Management of thyroid tumor can be problematic in developing countries due to
      poor diagnostic and therapeutic facilities. This is true in Burkina Faso where
      there are no facilities for radioisotope scans and intraoperative biopsy is
      usually unfeasible due to a shortage of histologists. The purpose of this
      retrospective analysis of the files of 83 patients who underwent surgery of the
      thyroid between January 1988 and December 1993 at the National Hospital Center of
      Ouagadougou was to obtain information necessary to define suitable pre-, per-,
      and post-operative strategies for these conditions. The mean delay to
      consultation for the 83 patients studied was 8 years. The fact that dysphonia
      and/or dysphagia was present at the first examination in 68 cases and that
      paralysis of the recurrent laryngeal nerve was observed in 17 cases testifies to
      the advanced stage at which patients were seen. Cancer was confirmed in only 3 of
      the 41 surgical specimens that were examined (7.3%). In cases involving only one
      nodule with no signs of malignancy, resection of the nodule is justifiable (18.1%
      of cases). In other cases radical resection is indicated either by lobo
      isthmectomy or subtotal thyroidectomy for diffuse or multinodular goiter (74.7%
      of cases) or by total thyroidectomy (7.2% of cases). The immediate postoperative
      period was marked by the occurrence of hemorrhage (n = 7), transient paralysis of
      the recurrent laryngeal nerve (n = 4), and infection of the surgical wound (n =
      5). There were 2 deaths.

PMID- 7637611
TI  - [Round pulmonary lesions after returning from French Guyana. Six cases of
      american pulmonary histoplasmosis].
AB  - From 1989 to 1994, 71 patients were hospitalized for diagnosis of round lung
      lesions including 49 servicemen under the age of 45 years who had been stationed
      in tropical areas. In 6 of these servicemen, the diagnosis was pulmonary
      histoplasmosis at the tertiary stage of histoplasmoma. All had done duty in
      French Guyana and were negative for human immunodeficiency virus. The subpleural
      lung opacity was the only lesion in 5 out of 6 patients and was calcified in 4
      out of 6 patients. Since skin tests with histoplasmin and serologic testing for
      histoplasmosis failed to achieve definitive diagnosis, surgical biopsy was
      performed by conventional thoracotomy in 2 cases and video-assisted thoracic
      surgery in 4 cases. The specimens obtained confirmed diagnosis of histoplasmosis
      on mycologic criteria in 3 cases and on a combination of findings including
      compatible histologic evidence in 3 cases. Treatment consisted in surgical
      excision of the nodules, for which video-assisted thoracoscopic surgery proved to
      be an excellent technique because of its simplicity and rapidity.

PMID- 7637612
TI  - [Severe pulmonary and meningeal cryptococcosis in an immunocompetent Cambodian].
AB  - A chest x-ray showing a large tumor-like opacity in the left lower lobe and
      endoscopy visualizing a budding mass suggested a diagnosis of bronchial carcinoma
      in a 55-year old, tobacco-smoking Cambodian who consulted for hemoptysis and
      altered general status. Histological study of bronchial biopsies allowed
      differential diagnosis of cryptococcosis. Serologic tests for human
      immunodeficiency virus were negative and there was no other cause of
      immunodepression. Left lower lobectomy was performed at the German hospital of
      the APRONUC in Phnom Penh. Examination of the surgical specimen confirmed massive
      bronchopulmonary cryptococcosis. Two months after the procedure the patient was
      readmitted for neuromeningial cryptococcosis that responded well to fluconazole.
      Another relapse occurred 5 months later and was treated using the same drug. The
      patient is currently in remission. An increasingly common deep mycosis that is
      serious but curable with proper treatment, cryptococcosis deserves the full
      attention of physicians working in Cambodia where, as in other tropical zones, it
      is likely that this infection will progress with the incidence of AIDS. Symptoms
      can be misleading, suggesting neuromeningial or pulmonary tuberculosis. The value
      of India ink smear which should be performed in all patients presenting
      lymphocytic meningitis with hypoglycorrhachia must be emphasized. In the present
      case bronchoscopy was useful to distinguish from bronchopulmonary cancer.

PMID- 7637613
TI  - [Gastrointestinal and urinary parasitic infection in children at a regional
      hospital center in Togo: some epidemiological aspects].
AB  - To determine the impact of parasitic infection of the digestive and urinary tract
      in children living in a rural area of Togo, a retrospective study was conducted
      in a Pediatric Department of Kara, Togo. Results revealed that 35% of the 1610
      children between the ages of 0 and 16 years had positive tests for parasites in
      stools or urine and that 117 had more than one parasite. Trichomonas
      intestinalis, Entamoeba histolytica, Schistosoma mansoni and Necator americanus
      accounted for 86.5% of the parasitic infections observed. Parasitic infection was
      observed during the neonatal period and its incidence increased in males up to
      the age of 12 years and during the rainy months of the year. Study of associated
      diseases indicated that 56% of children with parasites also had malaria and that
      47% were anemic. Parasitic infection of the digestive and/or urinary tract was
      noted in 31.8% of children under the age of 5 years with malnutrition.

PMID- 7637614
TI  - [Tumor-related epilepsy in adults in Gabon: diagnostic problems and therapeutic
      management].
AB  - The incidence of supratentorial brain tumors revealed by epileptic seizure is
      certainly underestimated in developing countries due to the lack of adequate
      diagnostic facilities. This report describes 10 cases of tumor-related epilepsy
      observed in Gabon over a 54-month period. Tumor-related seizures accounted for 5%
      of patients hospitalized for epilepsy in neurosurgical and neurologic units in
      Gabon during the study period. In two patients who refused surgery, diagnosis of
      the tumor was made solely on angiographic findings. Surgery was performed in 8
      patients based on electroencephalographic and arteriographic findings. There were
      4 astrocytomas, 3 meningiomas, and 1 glioblastoma. One patient died 8 days after
      the procedure due to convulsions. Another patient was lost from follow-up three
      months after the procedure. The remaining 6 patients are asymptomatic with follow
      up periods ranging from 10 to 72 months (mean: 40.6 months). The value of early
      diagnosis and resection as well as post-operative use of antiepileptic drugs is
      emphasized.

PMID- 7637615
TI  - [Importance of drug carriers in the treatment of visceral leishmaniasis].
AB  - Visceral leishmaniasis is caused by hemoflagellate protozoa which are obligatory
      parasites of the mononuclear phagocyte system. Leishmaniasis causes high
      morbidity and mortality worldwide. The treatment of choice remains pentavalent
      antimonials, but high toxicity and failures have been reported. An alternative to
      conventional treatment is delivery anti-leishmania agents using colloidal carrier
      systems. Carriers improve drug activity against intracellular disease involving
      the mononuclear phagocyte system. The principle of drug delivery by carrier
      systems has been applied successfully for anticancer drugs. Recently complete
      remission of polyresistant visceral leishmaniasis was obtained by injection of
      liposomal amphotericin B. At present, no colloidal drug carrier for antimony
      derivatives is available, but pentamidine can be linked experimentally to
      methacrylate polymer nano-particles. Drug-loaded nanoparticles have been shown to
      be effective against amastigote leishmania both in vitro and in vivo. Another
      colloidal system of major interest for drug delivery, the liposome has already
      been loaded with amphotericin B and used for human therapy. The concept of
      particulate drug carriers opens the way for new chemotherapeutic approaches in
      the field of parasitology.

PMID- 7637616
TI  - [Cysticercosis: a frequent and redoubtable parasitic disease].
AB  - Cysticercosis is due to development of the larval form of Taenia solium,
      Cysticercus cellulosae in human tissue. It is widespread in developing countries
      especially in rural areas where it is endemic. Larval invasion of the central
      nervous system constitutes a dreadful complication. The incidence of this
      worldwide disease is underestimated in French-speaking Black Africa; the Indian
      ocean region has one of the highest incidences with Madagascar reporting a
      seroprevalence of 18% in 1994. It is estimated that 50 million people are
      infected in the world with 50,000 deaths a year. "Taenia solium carriers" play a
      major role in transmitting the disease to their immediate entourage even if the
      initial contamination of the carrier was due to infestation of pork. A wide range
      of epileptic manifestations can and often do constitute the first signs of
      neurocysticercosis which has been estimated to be the cause of epilepsy in two
      thirds of cases. This fact explains the numerous neuro-epidemiologic studies have
      been undertaken. In industrialized countries computeur tomodensitometry and
      magnetic resonance imaging are widely used for diagnosis and follow-up but
      immunologic diagnosis is most common in developing countries since medical
      imaging techniques are generally unavailable. The immuno-enzymatic method
      provides a basis for suspicion of infection and immuno-electrotranfer-blot allows
      diagnosis of progression of the disease to a stage at which cestocide treatment
      is active. New agents against cysticercoids that can circulate in the central
      nervous system (praziquantel, albendazole) have greatly improved the prognosis of
      neurocysticercosis. Massive single-dose treatment with praziquantel is especially
      useful in developing countries since taeniasis is rarely diagnosed in Taenia
      solium carriers. Persistent efforts to prevent contamination of pork have
      eradicated the infection in industrialized countries and diminished
      seroprevalence in others (Reunion Island). Cysticercosis is a major public health
      problem in developing countries. Systematic detection of the hotbeds and
      application of adequate control measures are needed.

PMID- 7637617
TI  - [Cambodia: creation of a university hospital center at Calmette Hospital. A new
      start for french medical cooperation?].
AB  - In Cambodia, reconstruction of the hospital facilities remaining after the
      widespread destruction of the health system that occurred in 1970 has been under
      way since 1990. France has officially committed itself to re-organizing the
      Cambodian health care system and is playing a leading role in several projects.
      Technical assistance is provided at the Calmette Hospital, which provides not
      only practical training but also as a wide range of medical services with a 220
      bed facility including medical departments, surgical departments, an intensive
      care department and a surgical theater. The objective is to reorganize the
      facility, update the training of staff and the available technology, and
      currently create an emergency care department. At the combined Faculty of
      Medicine, Pharmacy, and Odontology, restructuring is being managed by the French
      adviser to Dean who is in charge of training faculty and improving the quality of
      instruction which implies the assistance from French university professors. At
      the beginning of 1995, a new Pasteur Institute will open. The Calmette Hospital,
      the combined Faculty and the PASTEUR Institute constitute the University Hospital
      Center in Cambodia.

PMID- 7637618
TI  - [Madagascar: from Isoavinandriana to Soavinandriana or the remarkable history of
      the Girard and Robic Hospital].
AB  - The history of the Soavinandriana Hospital is remarkable for several reasons. The
      oldest hospital on the island, this institution is the product of the combined
      efforts of English Christian missionaries, French colonists, and native
      Madagascans. Its history has always been closely linked to political events in
      Madagascar and the successive names often reflect Franco-Malagasy relations. The
      hospital which was long the crown jewel of the "colonial" health corps still
      provides a framework for harmonious cooperation between French and Malagasy
      military physicians. The institution has always been on the forefront of medicine
      in Madagascar and, despite current problems, is still the best-equipped health
      facility on the island. Thanks to the quality of care and the dedication and
      competence of its staff, the hospital has succeeded in maintaining patient
      attendance from all classes of society. The hospital which in its over 100-year
      history has witnessed two momentous occasions with the visits of the last Queen
      and the first President of the Republic now stands on the threshold of a
      renaissance and could become a model for successful Franco-Malagasy cooperation.

PMID- 7637619
TI  - Vein conduits for repair of nerves with a prolonged gap or in unfavourable
      conditions: an analysis of three failed cases.
AB  - Clinical failure of vein conduits for repair of four nerves in three cases is
      reported. Two digital nerves with gaps of 5.0 cm and 5.8 cm, respectively, and
      two median nerves with gaps of 4.0 cm and 5.0 cm were repaired with vein
      conduits. The digital nerves were repaired secondarily with insertion of nerve
      tissue slices. The median nerve lacerations were associated with compound soft
      tissue injuries and were repaired primarily by interfascicular vein conduits.
      There was no detectable recovery of sensibility in autonomous areas of these
      nerves and no sign of recovery of the innervated muscles during follow-up. Re
      exploration revealed that the vein conduits used for repair of the median nerves
      were constricted by surrounding scar tissue and axon regeneration was precluded.
      The critical length for nerve regeneration in human beings and wound conditions
      unfavorable to nerve regeneration are discussed. This report suggests that vein
      conduits are not indicated in nerve gaps over 5.0 cm or in primary repair of
      nerves with compound injuries.

PMID- 7637620
TI  - Natural history of digital replantation: a 12-year prospective study.
AB  - The purpose of the study was to evaluate the fate of the digital arterial
      anastomoses, resting total digit blood flow, and cold-induced discomfort
      following digital replantation with two repaired arteries. The evaluation was
      done with a Doppler ultrasound of the anastomoses, temperature recording from the
      finger pulp at room temperature, and a questionnaire regarding the patient's
      impression of cold-induced discomfort. At the 2-year follow-up all anastomoses
      were patent, but in two of the six patients one anastomosis was occluded at the
      12-year follow-up. The replanted digits generally showed lower skin temperatures
      compared with controls at the 2-year follow-up but these had normalized 10 years
      later, even in digits with one of the two repaired arteries occluded. The number
      of patients with severe cold-induced discomfort was unchanged during the
      observation period. CONCLUSION: The digital flow continues to increase after the
      first 2 years after replantation and may reach normal levels at room temperature;
      however, cold-induced discomfort is not normalized. Total blood flow improvement
      is not affected by late arterial occlusion.

PMID- 7637621
TI  - Axillary plexus blockade in microvascular surgery, a steal phenomenon?
AB  - A case report is presented of an axillary plexus blockade following a second toe
      to-hand transfer. After completion of the microvascular anastomoses and
      restoration of blood flow to the transplanted toe, the axillary plexus blockade
      was started. Together with the vasodilation of the hand and forearm there was a
      marked drop in blood flow in the transplanted toe. Possible explanations for this
      phenomenon are considered. We suggest starting axillary plexus blockade before
      completion of microvascular anastomoses and maintaining a continuous
      postoperative blockade.

PMID- 7637622
TI  - Anatomic study of a new axial skin flap based on the cutaneous branch of the
      medial plantar artery.
AB  - A new axial skin flap based on the middle cutaneous branch of the medial plantar
      artery was evaluated in 33 fresh cadaver legs. The vascular pedicle of the skin
      flap is based on the middle cutaneous artery, its venae comitantes, and segments
      of the great saphenous vein, if necessary. The middle cutaneous artery is the
      largest cutaneous branch, arising from the medial plantar artery 2.5 cm distal to
      its origin. The diameter of its origin is 1.2 mm, and its pedicle is 2 cm long.
      The midline of the flap runs from the first web space to the heel tip. The upper
      and lower borders of the flap are 3 to 4 cm on either side of this line. The
      upper border is medial to the extensor hallucis tendon, and the lower border is
      medial to the abductor hallucis. Distally, the border begins 2 cm proximal to the
      metatarsalphalangeal joint; proximally, the border is at the middle of the medial
      malleolus. The flap diameter can be up to 8 x 12 cm. The middle cutaneous branch
      of the medial plantar artery was found in all cadaver specimens, except for one
      with a common trunk. The new flap design leaves the major blood supply to the
      foot and the plantar aponeurosis intact. It is easy to harvest and may be used
      either as an island flap or free flap.

PMID- 7637623
TI  - Revascularisation versus reconstruction of degloving injuries of the heel: case
      report.
AB  - The anatomy of heel vascularization implies that there is a high risk of necrosis
      if degloved soft tissue is only sutured back to its former position. Two patients
      who had sustained similar degloving injuries of the heel are presented. One of
      them was treated by primary revascularization and the other by secondary
      reconstruction with a dorsalis pedis flap. The postoperative outcome was
      investigated to show the value of the salvage operation. Dynamic pressure
      distribution gait analysis was performed barefoot and in the shoe to investigate
      postoperative weightbearing on the reconstructed areas. In contrast to the heel
      reconstruction with the dorsalis pedis flap, the revascularized original heel was
      stable without development of soft tissue lesions. The salvaged original heel
      tissue enabled a physiologic pressure distribution beneath the heel and a more
      physiological rollover process of the foot, comparable to the contralateral foot.
      In degloving injuries of the heel, revascularization of the soft tissue should be
      considered whenever possible.

PMID- 7637624
TI  - Can quantitative 99mTc-MDP bone scans be used to predict longitudinal growth of
      epiphyseal plate allografts after microvascular transplantation? An experimental
      study.
AB  - Allograft and autograft microvascular proximal tibial epiphyseal plate
      transplants were performed in female New Zealand White (NZW) rabbits to quantify
      the growth rate and total growth potential of immunosuppressed and
      nonimmunosuppressed rabbits. The purpose of this experiment is to examine whether
      the 99mTc-MDP radionuclide uptake of the transplanted epiphyseal plate at 1 week
      postoperatively, done to assess anastomotic patency of the transplant, could also
      serve as a predictor of eventual longitudinal growth of the transplant or
      replant. All transplants and replants demonstrating positive 99mTc-MDP uptake in
      the proximal tibial epiphyseal plate at 1 week showed continued longitudinal
      growth. The precise amount of 99mTc-MDP uptake, however, did not correlate with
      the amount of growth at 3 and 5 weeks follow-up.

PMID- 7637625
TI  - Reconstructive microsurgery of lymph vessels: the personal method of lymphatic
      venous-lymphatic (LVL) interpositioned grafted shunt.
AB  - Our clinical observations in 64 patients affected by chronic obstructive
      lymphedema (either arm or leg) undergoing interposition autologous lymphatic
      venous-lymphatic (LVL) anastomoses are reported. This microsurgical technique is
      an alternative to other lymphatic shunting methods, especially when venous
      dysfunction coexists in the same limb and, therefore, when direct lymphatic
      venous anastomosis is accordingly inadequate. Preoperative diagnostic evaluation
      (including lymphatic and venous isotopic scintigraphy, Doppler venous
      flowmetrics, and pressure manometry) plays an essential role in assessing the
      conditions of both the lymphatic and venous systems and in establishing which
      microsurgical procedure, if any, is indicated. Our microsurgical technique
      consists of inserting suitably large and lengthy autologous venous grafts between
      lymphatic collectors above and below the site of obstruction to lymph flow. The
      data show that, using this technique, both limb function and edema improved, and
      in all patients followed up for over 5 years edema regression was permanent.

PMID- 7637626
TI  - Orthotopic liver retransplantation in rats.
AB  - A surgical experience with a method of rate orthotopic liver retransplantation
      (OLRT), and a preliminary study of immunological responses after OLRT are
      reported. OLRT was performed on the same recipient after the fist orthotopic
      liver transplantation (1st-OLT) according to our original (Kamada's) cuff method.
      Replacement of the portal vein (PV) and infra-hepatic vena cava (IHVC) cuffs was
      not technically difficult. However, there were no survivors from the first 6
      retransplanted rats, mainly due to complications from defective supra-hepatic
      vena cava (SHVC) anastomoses. Unlike the human intra-abdominal SHVC, the
      posterior wall of the intra-abdominal SHVC in rats is too short and fragile to
      perform an end-to-end anastomosis twice between donor and recipient SHVC. For a
      second group of seven retransplants, a modification of the SHVC anastomosis was
      made between donor and recipient SHVC in conjunction with the recipient's cuff
      diaphragm. This enabled reanastomosis to be secure, resulting in the improved 1
      week survival after isogenic OLRT (85.7%). This OLRT model has been applied to
      the fully allogeneic combination for several immunological studies and led to
      novel findings. Thus, an experimental model of a rat orthotopic liver
      retransplant model has the potential to allow more valuable insights into the
      immunological study of chronic rejection, sensitization and chimerism following
      liver retransplantation.

PMID- 7637627
TI  - SFI = sciatic functional index? Or some feebler imitation?

PMID- 7637628
TI  - [Examination of health effects after exposure to metallic mercury vapors in
      workers engaged in production of chlorine and acetic aldehyde. I. Evaluation of
      general health status].
AB  - Physical, neurological and psychological examinations as well as laboratory tests
      were performed in the group of 147 workers, engaged in the production of
      chlorine, acetic aldehyde and soda lye, exposed to metallic mercury vapours and
      in the control group (n = 49). In the evaluation of laboratory tests, morphology
      of peripheral blood, liver function tests and lipid balance were analysed in the
      first part of the work. Electroencephalography, electrocardiography and chest X
      ray were also performed as auxiliary examinations. There was a certain percentage
      of cases with symptoms of organic damage of the brain mostly in the form of
      cerebellar syndrome. Psychological organic tests proved to be of little value in
      the evaluation of effects of exposure to mercury. The results suggest that
      occupational exposure to metallic mercury vapours can enhance the risk of
      hypertension and myocardial failure. Harmful effect of occupational exposure to
      metallic mercury vapour on the respiratory and haemopoietic systems as well as on
      the liver and lipid balance was not observed.

PMID- 7637629
TI  - [Mortality in a cohort of workers working with pulp and paper].
AB  - Mortality among workers in the Polish pulp and paper industry was evaluated in
      retrospective cohort study of 10460 workers who had been employed continuously
      for at least one year between 1968 and 1990 in the factory producing sulphate
      pulp, paper, board and paper products. A standardized mortality ratio (SMR)
      analysis was used to compare death rates for the exposure group with Polish
      national rates. For all the subjects death due to all causes and all malignant
      neoplasms were lower than the number expected. The only significantly increased
      risks were those of malignant neoplasm of brain among women (4 cases, SMR = 318)
      and of retroperitoneum and peritoneum among men (2 cases, SMR = 659), exposed to
      high level of wood dust and irritant sulphur compounds. The authors could not
      find any etiological explanation of the excessive mortality from brain and
      peritoneum cancers.

PMID- 7637630
TI  - [Acquired color vision disturbances as a sensitive marker of chronic exposure to
      petroleum derivatives].
AB  - The Farnsworth-Munsell 100 Hue test was used to examine 75 males aged 25-60 years
      before and after a break in exposure to petroleum derivatives and 30 males non
      occupationally involved in the petrochemical industry. Acquired colour vision
      disturbances were found in 29% of those under study before and in 16% after a
      break in exposure and rest while in the control group they were diagnosed in 17%
      of subjects before and in 7% after rest. Remission of acquired dyschromatopsia of
      the blue and yellow axis was most commonly observed. This kind of disturbances
      accounted for 70% out of all disorders found in the basic group and they
      represented the only kind of disorders detected in the controls. An observed
      tendency towards remission of disturbances in the blue and yellow axis indicates
      a functional nature of the visual analyzer damage. Dyschromatopsia of the blue
      and yellow axis with concomitant disturbances in the red and green axis or
      without specified axis is more persistent and may indicate an organic damage of
      the route that transmits information about colours.

PMID- 7637631
TI  - [Evaluation of the relationship between concentration of serotonin in plasma and
      blood platelets and hypertension in women chronically exposed to carbon
      disulfide].
AB  - Totally 140 women, aged 25-50 years, were examined clinically. They were divided
      into two groups. Group I, the controls, (n - 50; mean age 40.1 +/- 8.7) not
      exposed to carbon disulfide, and Group II (n = 90; mean age 39.7 +/- 9.1) exposed
      to carbon disulphide at concentration of 9.36-23.4 mg/m3. Concentration of
      serotonin in plasma and blood platelets was determined using Manuchin's
      colorimetric method. Student t-test and the Pearson linear correlation
      coefficient "C" were used for statistical analysis. It was found that women
      chronically exposed to carbon disulfide showed significantly higher values of
      serotonin concentration in plasma and thrombocytes (p < 0.001) that the controls.
      Also positive linear correlation was noted between concentration of serotonin and
      hypertension in women exposed to CS2.

PMID- 7637633
TI  - [Preliminary assessment of the effect of disinfectants on skin changes in health
      service workers].
AB  - During a five-year period (1 Jan. 1989 and 31 Oct. 1994) epidermal tests with
      disinfectants (formalin, sterinol, lysoformin, aldesan, septyl, chloramine,
      lysol, chlorhexidine) and their components (glutaraldehyd, phenol, hydroquinone)
      were performed on 322 health service workers examined at the Nofer Institute of
      Occupational Medicine due to suspected occupational dermatitis. It was found that
      89 (27.6%) subjects examined were oversensitive, at least, to one disinfectant,
      mostly to formalin, sterinol (benzalkonium bromide), lysoformin and chloramine.
      Frequent occurrence of allergy to metals (nickel, cobalt, chromium, mercury) was
      observed in persons oversensitive to disinfectants.

PMID- 7637632
TI  - [Selected biomarkers for evaluating occupational exposure to lead among workers
      from the "Miasteczko Slaskie" zincworks in Tarnowskie Gory].
AB  - A dose-response relationship between exposure to lead and delta-aminolaevulinic
      acid concentration in urine (ALA-U), and between blood lead (Pb-B) and zinc
      protoporphyrin IX (ZPP-B) concentrations in blood were examined in 90 male
      workers exposed to lead. Concentrations of ZPP-B correlated closely with blood
      lead levels. Concentrations of ALA-U ranged from 1.6 to 19.4 mg/l. These data
      suggest that ALA-U is a useful indicator of early effects of exposure to lead on
      heam biosynthesis. Lead concentrations in air at different work posts were
      analysed. The results obtained were compared with the levels of standard values
      of lead concentrations in air and with blood lead levels at those work posts.

PMID- 7637634
TI  - [Analysis of diagnostic X-Ray units in Poland in view of patients' exposure to
      ionizing radiation].
AB  - An analysis of diagnostic X-ray units in Poland is presented. The air-kerma on
      the X-ray table was measured for X-ray parameters used routinely during lumbo
      sacral spine radiography in a standard patient. The measurements were performed
      using TLD made of lithium-fluoride. The dose received by patients in different X
      ray departments is sometimes higher than two orders of magnitude from 0.14 mGy to
      72.11 mGy for the same examination. The dose can be significantly reduced if the
      cassettes with amplyfying foils, made from rare earth components, are used.

PMID- 7637635
TI  - [Impact of different solvents on results of genotoxicity studies of airborne dust
      taken from work environments].
AB  - Mutagenicity and toxicity of extracts of airborne particulate matters, sampled
      during electrolysis of aluminium, cooking of coal and low-temperature
      carbonization processes, were determined by the Salmonella plate incorporation
      assay with strains TA98 and TA100. Organic materials were extracted with benzene,
      cyclohexane or toluene from airborne particles by sonication. The results showed
      that: a) the extracts were mutagenic only to strain TA98 (without and after
      metabolic activation); b) there was a similar efficiency of applied solvents in
      extraction of mutagenic substances detectable with TA98, and c) the toluene
      extracts were most toxic towards test bacteria TA98.

PMID- 7637636
TI  - [Evaluation of the nervous system in workers needed for preventive examinations.
      III. Indications for neurological consultation].
AB  - The reasons why a physician who carries out preventive examinations, including
      certain aspects of the nervous system assessment, should refer a particular
      worker to a neurologist for consultation are identified. Indications for the
      consultation by a specialist are divided into those resulting from taking a case
      history, aberrations observed during a physical examination and kind of patient's
      job. Indications most common in the day-to-day practice are discussed thoroughly.

PMID- 7637637
TI  - [Use of bronchoalveolar lavage for diagnosis of respiratory diseases].
AB  - Examination of bronchoalveolar lavage fluid is a method based on obtaining
      biological material in the from of cells and fluid derived directly from the
      alveoli of the bronchi. Cytological and biochemical examination of the
      bronchoalveolar fluid enables to understand pathomechanisms of various
      interstitial and obstructive pulmonary diseases. Bronchoalveolar lavage (BAL) is
      a sensitive and safe diagnostic method, which becomes to be widely employed in
      the pneumonologic++ diagnosis.

PMID- 7637638
TI  - [Amorphous silica. Types, health effects of exposure, NDS].
AB  - Maximum allowable concentration (MAC) values for amorphous silica dust have not
      been identified in the Polish legal regulations up-to-date. In this work the
      authors review values of allowable (recommended) amorphous silica dust
      concentrations in other countries. Data on other types of amorphous silica
      (natural and synthetic) used in industry as well as data on health effects of
      exposure to these types of dust are presented. The work encompasses 42 entries in
      the references and one Table which includes the following proposed MAC values:
      Non-calcinate diatomaceous earth (diatomite) and synthetic silica: Total dust--10
      mg/m3 Respirable dust--2 mg/m3 Calcinate diatomaceous earth (diatomite) and fused
      silica (vitreous silica): Total dust--2 mg/m3 Respirable dust--1 mg/m3.

PMID- 7637639
TI  - [Legal status of occupational health in Poland--current status and proposal of
      changes].

PMID- 7637640
TI  - Modulation of glycogen phosphorylase activity and fructose 2,6-bisphosphate
      levels by glibenclamide and meglitinide in isolated rat hepatocytes: a
      comparative study.
AB  - The influence of glibenclamide and meglitinide, or 4-[2-(5-chloro-2
      methoxybenzamide)ethyl]-benzoic acid, a compound similar to the nonsulfonylurea
      moiety of glibenclamide, on glycogen phosphorylase a activity, fructose 2,6
      bisphosphate (F-2,6-P2) level, and cytoplasmic free-Ca2+ concentration has been
      studied in isolated rat hepatocytes. Both glibenclamide and meglitinide caused a
      transient and dose-dependent activation of glycogen phosphorylase, with half
      maximal effects corresponding to 3.7 +/- 1.6 and 9.6 +/- 3.3 mumol/L,
      respectively. This enzyme activation occurred without significant changes in
      hepatocyte cyclic adenosine monophosphate (cAMP) levels and was accompanied by an
      increase in cytoplasmic concentration of free Ca2+. Parallel to these effects,
      glibenclamide increased the cellular content of F-2,6-P2, with this effect being
      associated with a reduction in the rate of glucose formation from a mixture of
      [14C]lactate/pyruvate. Under similar conditions, meglitinide caused a significant
      reduction of F-2,6-P2 levels and accelerated the gluconeogenic flux. The
      mechanism by which meglitinide decreases hepatocyte F-2,6-P2 levels seems to be
      mediated by stimulation of fructose-2,6-bisphosphatase. This comparative study
      may help to elucidate which among the hepatic effects of glibenclamide are
      exerted specifically by the sulfonylurea moiety.

PMID- 7637641
TI  - Effect of loop diuretics and nonsteroidal antiinflammatory drugs on thyrotropin
      release by rat anterior pituitary cells in vitro.
AB  - The close inverse-feedback relationship between serum free thyroxine (T4) and
      thyrotropin (TSH) is altered in some patients receiving therapeutic doses of
      drugs such as furosemide, fenclofenac, and diphenylhydantoin. We therefore
      examined the effect of nonsteroidal antiinflammatory drugs (NSAID), diuretics,
      and diphenylhydantoin on TSH release in rat anterior pituitary cells in primary
      culture. TSH content of the culture medium was measured at 22 hours at 37 degrees
      C either with or without thyrotropin-releasing hormone ([TRH] 10 nmol/L) in
      medium containing 0.5% bovine serum albumin. The mean basal TSH release by
      pituitary cells was 6.2 +/- 1.2 ng/mL (n = 10) and was not influenced by
      unlabeled triiodothyronine ([T3] 100 nmol/L) or any of the drugs tested at < or =
      400 mumol/L, except ethyacrynic acid. TRH 10 nmol/L increased mean TSH release by
      346% +/- 95% (n = 10). T3 1 and 100 nmol/L inhibited TRH-stimulated TSH release
      by 24% and 31%, respectively (P < .001), whereas TRH-stimulated TSH release was
      inhibited by 100 mumol/L meclofenamic acid (29%), fenclofenac (28%), furosemide
      (24%), and diphenylhydantoin (48%) (P < .001 v TRH alone). Meclofenamic acid and
      furosemide (100 mumol/L) did not significantly alter the inhibitory effect of T3
      1 nmol/L on TRH-stimulated TSH release. These in vitro studies suggest that
      meclofenamic acid, fenclofenac, furosemide, and diphenylhydantoin could influence
      TSH release by attenuating the TSH response to TRH. This effect may influence T4
      TSH relationships when these agents are used in vivo.

PMID- 7637642
TI  - Testosterone treatment in adolescent boys with constitutional delay of growth and
      development.
AB  - Administration of androgens to adolescent boys with constitutional delay in
      growth has been highly controversial. One hundred forty-eight adolescent boys
      with constitutional delay of growth and puberty with a mean age of 14.3 +/- 0.7
      years were treated with testosterone enanthate 100 mg intramuscularly each month
      for 6 months. Growth parameters, sexual maturation, and circulating
      concentrations of testosterone and insulin-like growth factor-I (IGF-I) were
      compared with those for 50 age-matched adolescent boys with constitutional delay
      of growth and puberty with a mean age of 14.1 +/- 0.9 years who did not receive
      any treatment. The mean height growth velocity, height standard deviation score,
      weight gain, and IGF-I concentration were significantly greater in the treatment
      group after 1 year of follow-up evaluation. The advancement in bone age equaled
      that in chronologic age in the treatment group, with no significant change in the
      bone age to chronologic age ratio (BA/CA) before versus after therapy. All
      subjects in the treatment group had clearly entered puberty by the end of 1 year.
      Testicular size increased significantly in the treatment group and they had
      significantly higher serum testosterone concentrations 6 months after the end of
      testosterone therapy as compared with the control group, denoting activation of
      the hypothalamic-pituitary testicular axis. All subjects in the treatment group
      were psychologically satisfied with the enhanced growth and increased muscle
      mass, versus only 40% of those in the control group. In conclusion, our regimen
      appears to be efficacious and safe for treatment of boys with constitutional
      delay of growth and puberty and has no deleterious effect on skeletal age.

PMID- 7637644
TI  - Is obesity-related insulin status the cause of blunted growth hormone secretion
      in Turner's syndrome?
AB  - Growth hormone (GH) secretion is reduced in girls with Turner's syndrome (TS) at
      pubertal age. We have recently proposed that the impairment of GH release in TS
      girls might be secondary to obesity. In the present study, we assessed the
      influence of overweight-related insulin status on spontaneous GH secretion in a
      group of 15 TS girls. Eighteen age-matched short normal subjects and six short
      obese prepubertal children were chosen as controls. Anthropometry, spontaneous GH
      secretion, insulin-like growth factor-I (IGF-I) serum levels, basal fasting
      insulin, and glucose concentrations were determined. The percentage of ideal body
      weight (IBW) was used as an index of nutritional status. Baseline fasting glucose
      (milligrams per deciliter) to insulin (milliunits per liter) ratio (G/I) was
      chosen as an index of insulin resistance. GH secretion was significantly lower in
      TS girls than in non-obese children (P < .005), whereas no significant difference
      was seen between TS and obese subjects. IGF-I levels were not statistically
      different in all groups. GH secretion was confirmed to be related to the degree
      of overweight (r = -.52, P < .05 in TS girls and r = -.74, P < .0001 in control
      group). G/I was closely related to both the percentage of IBW (r = -.59, P = .02)
      and GH level (r = .57, P = .03) in TS patients. These results confirm that the
      blunted GH secretion in TS patients is dependent on nutritional status, and
      suggest that insulin resistance secondary to overweight might represent the
      pathophysiologic link between the obesity-related metabolic status and impaired
      GH secretion.

PMID- 7637643
TI  - Patients undergoing coronary artery bypass graft surgery are at high risk of
      impaired glucose tolerance and diabetes mellitus during the first postoperative
      year.
AB  - This study demonstrates that patients who have undergone coronary artery bypass
      graft (CABG) surgery have a high prevalence of abnormal glucose tolerance 3
      months and 1 year later. Although only 6% were known to have diabetes mellitus
      (DM) preoperatively, a further 4% were classified DM at two oral glucose
      tolerance tests (OGTTs) over the subsequent year and a further 18% were
      classified as having impaired glucose tolerance (IGT) at 12 months.
      Reproducibility of the 120-minute plasma glucose level in the 75-g OGTT was
      estimated from a repeat test performed within 10 days. The coefficient of
      variation (CV) of 120-minute glucose was between 14% and 18%. The observed
      changes in class of glucose tolerance observed at OGTTs repeated 6 and 12 months
      after surgery differed from the predicted changes based purely on the estimated
      variability of 120-minute glucose measurement. There was evidence of regression
      to the mean for the IGT group. However, there was also evidence of deteriorating
      glucose tolerance in some subjects. Between 4% and 9% of those with IGT 3 months
      after CABG surgery developed DM by 12 months, and 26 (13%) of those with
      initially normal glucose tolerance (NGT) developed IGT. Insulin and glucose
      responses in the OGTT and estimates of insulin resistance and beta-cell function
      from fasting samples show that insulin resistance was the principal abnormality
      in IGT subjects, whereas in DM subjects, both insulin resistance and beta-cell
      dysfunction contributed. Analysis of preoperative patient characteristics showed
      that the presence of either a systolic blood pressure of 140 mm Hg or body mass
      index (BMI) of more than 25 kg/m2 identified 51% of the subjects who would at 1
      year after surgery include all those who would be classified DM and 67% of those
      who would have IGT. Further analyses including insulin levels identified groups
      at particularly high risk of DM, but no combination of readily available
      preoperative measures identified all those destined to be classified IGT.

PMID- 7637645
TI  - Regulation of growth factor mRNA levels in the eyes of diabetic rats.
AB  - The underlying etiology of diabetic microvascular disease remains unknown. To
      examine the potential contribution of basic fibroblast growth factor (bFGF),
      which is an angiogenic factor, and insulin-like growth factor-I (IGF-I) to the
      development of diabetic microvascular disease, bFGF and IGF-I mRNA levels were
      measured in tissues of control, diabetic, and insulin-treated diabetic rats.
      Diabetes was induced in rats by intravenous injection of streptozotocin (STZ) 65
      mg/kg, and the rats were maintained for 21 days. bFGF mRNA levels increased
      threefold in the eyes of diabetic versus control rats, whereas a consistent
      change in bFGF mRNA levels was not observed in other tissues. In contrast, IGF-I
      mRNA levels decreased in the eyes and other tissues, including kidney, lung, and
      skeletal muscle, of diabetic as compared with control rats. Insulin treatment
      prevented the diabetes-induced increase in bFGF and decrease in IGF-I mRNA
      levels. Acidic FGF (aFGF) mRNA levels were unchanged in eyes from diabetic versus
      control rats. In partially purified retinas, diabetes increased bFGF mRNA levels
      twofold as compared with levels in control retinas, whereas IGF-I mRNA levels
      decreased to 58% of control levels in retinas from diabetic rats. Insulin
      treatment again prevented the diabetes-induced increase in IGF-I mRNA levels in
      the retina but had no effect on the diabetes-induced increase in bFGF mRNA
      levels. bFGF peptide levels were minimally increased in diabetic versus control
      retinas.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7637646
TI  - Energy cost of physical activities in healthy elderly women.
AB  - In recent studies, daily physical activity ratios (PARs) greater than the Food
      and Agriculture Organization/World Health Organization/United Nations University
      (FAO/WHO/UNU) reference value of 1.5 have been reported for elderly men and
      women. The purpose of this study was to investigate whether a high PAR in elderly
      subjects can be explained by a higher energy cost of physical activities (EEact).
      To this end, 12 elderly women aged 69 to 82 years, completed physical activity
      diaries during a 2-day stay in a respiration chamber. From these diaries, total
      daily energy expenditure (TEE) in the calorimeter was estimated (TEEfac) using
      FAO/WHO/UNU PARs for physical activities and measured resting metabolic rate
      (RMR). TEEfac was 7.0 +/- 0.9 MJ/d (PAR, 1.35 +/- 0.06). TEE was also measured in
      the chamber (TEEcal) and was 8.3 +/- 1.3 MJ/d (PAR, 1.60 +/- 0.16). TEEfac was
      14.8% +/- 8.1% lower than TEEcal. To investigate whether the underestimation of
      TEEcal was due to a higher EEact in the elderly women as compared with the
      FAO/WHO/UNU references, EEact of six specific activities ranging from sitting at
      rest to walking on a treadmill at self-chosen speed was measured with a
      ventilated-hood system. Individually measured PARs of the six activities were
      similar to FAO/WHO/UNU reference PARs. This study suggests that in elderly women
      a high TEEcal is not explained by EEact during nonstandardized physical
      activities performed at self-chosen speeds. Whether these results can be
      extrapolated to the free-living environment needs to be investigated further.

PMID- 7637647
TI  - Direct correlation between cholesterol synthesis and hepatic secretion of
      apolipoprotein B-100 in normolipidemic subjects.
AB  - The regulation of apolipoprotein B-100 (apo B) metabolism in man is not fully
      understood. In vitro studies suggest a key role for the hepatic availability of
      cholesterol substrate. We therefore examined whether there was a direct
      association between plasma mevalonic acid (MVA) concentration (an index of in
      vivo cholesterol synthesis) and hepatic secretion of very-low-density lipoprotein
      (VLDL) apo B in eight normolipidemic, healthy adult subjects. Hepatic secretion
      of VLDL apo B was estimated by endogenous labeling of apo B with an 8-hour
      primed, constant infusion of 1-13C-leucine. Isotopic enrichment of VLDL apo B was
      measured by gas chromatography-mass spectrometry (GCMS), from which the
      fractional secretion rate (FSR) was derived by a modified monoexponential
      function. Plasma concentration of MVA was measured by gas chromatography-electron
      capture mass spectrometry in blood samples taken at 9 AM. The absolute secretion
      rate (ASR) of VLDL apo B (mean +/- SD) was 9.7 +/- 2.6 mg/kg/d, and MVA
      concentration was 5.0 +/- 2.5 ng/mL. There was a highly significant positive
      correlation between ASR of VLDL apoB and plasma MVA (r = .88, P = .004), which
      persisted after adjusting for apo E phenotype. The findings suggest that in vivo
      cholesterol synthesis is a determinant of hepatic secretion of apo B in
      normolipidemic subjects.

PMID- 7637648
TI  - Relationships of plasma and hepatic variables with rates of plasma low-density
      lipoprotein apolipoprotein B metabolism in baboons fed low- and high-fat diets.
AB  - These studies were conducted to determine relationships of plasma low-density
      lipoprotein (LDL) cholesterol concentrations and hepatic mRNA levels for
      apolipoprotein (apo) B, LDL receptor, and hepatic hydroxymethyl glutaryl coenzyme
      A (HMG CoA) synthase with plasma LDL apo B production and catabolic rates in
      baboons maintained on a low-cholesterol, low-fat chow diet and on a high
      cholesterol, high-fat (HCHF) diet. Twelve baboons with LDL cholesterol levels
      ranging from low to high on the HCHF diet but with similar high-density
      lipoprotein (HDL) cholesterol levels were selected from a colony of selectively
      bred pedigreed baboons. LDL apo B turnover and hepatic mRNA concentrations for
      apo B, LDL receptor, and HMG CoA synthase were measured on a chow diet and again
      on a HCHF diet fed for 14 weeks. LDL apo B fractional catabolic rates decreased
      and production rates increased on the HCHF diet. Hepatic mRNA concentrations for
      apo B were not affected by the HCHF diet. Hepatic LDL receptor and HMG CoA
      synthase mRNA concentrations decreased on the HCHF diet as compared with the chow
      diet. LDL apo B fractional catabolic rate was negatively correlated with plasma
      cholesterol, LDL cholesterol, LDL apo B, and LDL apo B production and positively
      correlated with hepatic LDL receptor and HMG CoA synthase mRNA concentrations and
      with plasma LDL triglyceride to cholesterol ratio on the chow diet but not on the
      HCHF diet. LDL apo B production was positively correlated with plasma
      cholesterol, LDL cholesterol, and LDL apo B on the HCHF diet and negatively
      correlated with LDL triglyceride to cholesterol ratio on both chow and HCHF
      diets.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7637649
TI  - Insulin secretion in insulin-resistant women with a history of gestational
      diabetes.
AB  - Women with a history of gestational diabetes mellitus (GDM) tend to be insulin
      resistant and hyperinsulinemic and are predisposed to the subsequent development
      of non-insulin-dependent diabetes mellitus (NIDDM). In the evolution of glucose
      intolerance, the first clinically detectable abnormality has not been defined and
      the relative importance of contributions of abnormal insulin secretion and
      insulin resistance is controversial. The present study was performed to evaluate
      the insulin secretory responses to oral and intravenous glucose and to mixed
      meals in women with a history of GDM, and to determine if the hyperinsulinemia
      present in these subjects is appropriate for the degree of insulin resistance. To
      address these questions, we studied the insulin secretory responses to oral
      glucose over a 3-hour period and to three mixed meals over a 24-hour period, and
      quantified the acute insulin response to glucose (AIRglucose) and insulin
      sensitivity (SI) during frequently sampled intravenous glucose tolerance tests
      (FSIVGTTs). Studies were performed in seven subjects with a history of GDM and in
      seven matched controls. Insulin secretion rates (ISRs) were derived by
      deconvolution of peripheral C-peptide values using a two-compartment model and
      standard C-peptide kinetic parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7637650
TI  - Insulin resistance is associated with abnormal dephosphorylation of a synthetic
      phosphopeptide corresponding to the major autophosphorylation sites of the
      insulin receptor.
AB  - Insulin resistance in the ob/ob mouse model is associated with a reduction in
      insulin-induced protein-tyrosine phosphorylation in tissues such as liver. To
      ascertain whether this decrease in phosphorylation may be due to increased
      phosphatase activity, protein-tyrosine phosphatase (PTPase) activity was
      determined in particulate and soluble fractions from livers of 5- to 23-week-old
      ob/ob mice and age-matched lean littermates. PTPase activity was measured using a
      synthetic phosphopeptide, TRDIY(P)ETDY(P)Y(P)RK, as the substrate, corresponding
      to residues 1142 to 1153 of the insulin receptor and containing the major
      autophosphorylation sites of the regulatory domain. The ob/ob mice were
      hyperinsulinemic across all age groups, but only the youngest mice (aged 5 to 7
      weeks) were hyperglycemic. Most PTPase activity was present in the liver
      particulate fraction and was 19% to 114% greater in ob/ob mice as compared with
      controls. PTPase activity in the liver soluble fraction was 26% less than control
      values in the youngest ob/ob mice (5 to 7 weeks), but increased with age and was
      41% and 131% above control values at 21 to 23 and 25 to 27 weeks of age,
      respectively. Oral administration of the PTPase inhibitor sodium orthovanadate
      (0.6 mg/mL in drinking water for 2 weeks) to young ob/ob mice caused a
      significant reduction in the elevated particulate PTPase activity, with
      concomitant decreases in plasma insulin and plasma glucose. Assessment of PTPase
      activity with a monophosphate form of the same synthetic peptide,
      TRDIY(P)ETDYYRK, showed lower PTPase activities as compared with the triphosphate
      form and no significant differences between ob/ob and control
      preparations.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7637652
TI  - Metabolic defects in persistent impaired glucose tolerance are related to the
      family history of non-insulin-dependent diabetes mellitus.
AB  - Recent studies have suggested that the family history of non-insulin-dependent
      diabetes mellitus (NIDDM) influences glucose metabolism in subjects with normal
      glucose tolerance (NGT). However, it is not known whether the family history of
      NIDDM influences glucose metabolism in impaired glucose tolerance (IGT). We
      studied in a well-characterized group the impact of family history of NIDDM
      (diabetes mellitus [DM]-positive) in subjects with IGT on glucose disposal rate
      (GDR) measured by the euglycemic hyperinsulinemic clamp technique combined with
      indirect calorimetry. We recruited subjects from our previous population-based
      studies, and verified their glucose tolerance status twice during the follow-up
      period of 1 year. Subjects with NGT (n = 10) and IGT (n = 18) were comparable
      with respect to age, sex distribution, body mass index, smoking habits, and
      hypertension. As a group, IGT subjects showed lower GDR than the NGT group (28.6
      +/- 12.1 v 38.9 +/- 13.6 mumol/kg/min, P < .05). IGT DM-positive subjects showed
      a 40% lower GDR than the NGT group (P < .05) and a 29% lower GDR than IGT DM
      negative subjects (P = NS). IGT DM-positive subjects had lower glucose oxidation
      (P = NS, P < .01), glucose nonoxidation (P = NS, P = .01), and suppression of
      lipid oxidation (P = NS, P < .05) during the hyperinsulinemic euglycemic clamp as
      compared with IGT DM-negative and NGT groups, respectively. In conclusion, in
      subjects with persistent IGT, the family history of NIDDM is associated with the
      reduced total whole-body, oxidative, and nonoxidative GDR.

PMID- 7637651
TI  - Postprandial lipoprotein responses in hypertriglyceridemic subjects with and
      without cardiovascular disease.
AB  - Three groups of age- and weight-matched men (aged 40 to 70 years) without
      diabetes were studied: controls (n = 10), plasma triglycerides (TG) less than 180
      mg/dL and no cardiovascular disease (CVD); HTG-CVD (n = 11), hypertriglyceridemic
      (HTG) (TG > 240 mg/dL) without CVD; and HTG+CVD (n = 10), HTG (TG > 240 mg/dL)
      with documented CVD. HTG+CVD subjects had higher fasting and post-oral glucose
      tolerance test insulin levels than the other two groups, respectively. Very-low
      density lipoprotein (VLDL)+chylomicrons (CMs), intermediate-density lipoprotein
      (IDL), low-density lipoprotein (LDL), and three high-density lipoprotein (HDL)
      subfractions (HDL-L, HDL-M, and HDL-D, from least to most dense) were isolated by
      gradient ultracentrifugation. Fasting lipoproteins were similar in HTG groups,
      except for higher VLDL lipid to apolipoprotein (apo) B ratios (P < .04) in the
      HTG+CVD group. Subjects were fed a high-fat mixed meal, and lipoprotein
      composition was determined at 3, 6, 9, and 12 hours postprandially. Postprandial
      responses of the core lipids (TG and cholesterol esters [CE]) in all of the
      lipoprotein subfractions were similar in the two HTG groups at each time point.
      However, both controls and HTG-CVD subjects had increases in HDL-M phospholipid
      (PL) at 9 and 12 hours with no change in HDL-D PL. The HTG+CVD group, on the
      other hand, had no increase in HDL-M PL and had a substantial reduction in HDL-D
      PL. These changes resulted in significant increases in HDL-M and HDL-D PL to apo
      A-I ratios in both controls and HTG-CVD subjects between 6 and 12 hours, whereas
      there was no increase seen in the HTG+CVD group. The HTG-CVD group also had a
      significantly greater increase in the VLDL+CM PL to apo B ratio (P = .038) at 3
      hours than the HTG+CVD group. This diminished amount of surface lipid per VLDL
      particle may account for the late decrease in the HDL-D PL to apo A-I ratio seen
      in HTG+CVD patients. There were no other postprandial lipid or apolipoprotein
      differences between the two HTG groups. We conclude therefore that the major
      postprandial lipoprotein abnormality in these HTG+CVD patients was a failure to
      increase the PL content per particle in VLDL+CM, HDL-M, and HDL-D. This
      abnormality could prevent the usual increase in reverse cholesterol transport
      seen in postprandial plasma and therefore contribute to their increased incidence
      of CVD. The greater insulin resistance seen in these patients also appears to
      contribute significantly to their CVD.

PMID- 7637653
TI  - Variations in plasma volume affect total and low-density lipoprotein cholesterol
      concentrations during the menstrual cycle.
AB  - Serum lipids are known to vary during the menstrual cycle. To determine if
      changes in plasma volume contribute to this effect, we determined serum lipids,
      lipoproteins, and estimated changes in plasma volume in 18 premenopausal women at
      the start of and at 5-day intervals after menstruation. Eleven men served as a
      comparison group. Changes in plasma volume were estimated from changes in
      hemoglobin and hematocrit. Total and low-density lipoprotein (LDL) cholesterol
      (mean +/- SD) increased 15 +/- 14 mg/dL (9% +/- 10%) and 11 +/- 13 (11% +/- 14%)
      within 10 days after the start of menstruation (P < .05) and then decreased
      toward baseline during the rest of the cycle. High-density lipoprotein (HDL)
      cholesterol increased 3 mg/dL, or 5%, (P < .05) on days 10 and 15 after
      menstruation. Plasma volume decreased 4% +/- 9% (P < .06) 10 days after the start
      of menstruation, and this maximum decrease in plasma volume coincided with peak
      increases in total, LDL, and HDL cholesterol. Except for an 8-mg/dL increase in
      LDL cholesterol at day 5, lipid changes were no longer significant after
      adjusting for changes in plasma volume. We conclude that alterations in plasma
      volume account for approximately half of the increase in total and LDL
      cholesterol during the menstrual cycle.

PMID- 7637654
TI  - Neurotensin decreases with fasting in the ventromedian nucleus of obese Zucker
      rats.
AB  - Neurotensin (NT) inhibits food intake when injected either in brain ventricles or
      in hypothalamic nuclei such as the ventromedian nucleus (VMN). NT concentrations
      are lower in obese than in lean Zucker rats in several hypothalamic nuclei,
      including the VMN. In this experiment, we studied the influence of the feeding
      state on NT concentrations in different brain areas of 10-week-old lean (n = 27)
      and obese (n = 27) Zucker rats that were fasted for 48 hours and then refed for 6
      hours. NT level was measured in the microdissected areas by radioimmunoassay.
      Obese rats ingested approximately 50% more food than lean rats in the ad libitum
      (ad lib) condition (P < .001) and 12% more during the refeeding time (NS). NT
      concentrations in the median eminence (ME) were 50% lower in obese than in lean
      rats (P < .001). This decrease could be related to a 20% decrease in the arcuate
      nucleus (ARC) of the obese rats (P < .04). NT concentrations in the ME and ARC,
      which are important for the control of pituitary hormone secretion by NT, were
      not changed by the feeding state in both genotypes. NT varied with the feeding
      state in the VMN only (P < .04). Concentrations were 45% lower in fasted (FD)
      obese rats than in ad lib or refed (RF) obese rats (1.09 +/- 0.25 ng/mg protein v
      1.98 +/- 0.36 ad lib and 1.62 +/- 0.11 RF, P < .05). They remained unchanged in
      lean rats. NT variations in the VMN of obese rats could contribute
      synergistically with other neuropeptides to the abnormal feeding behavior of
      these rats.

PMID- 7637655
TI  - Regulation of glucose transport in cultured muscle cells by novel hypoglycemic
      agents.
AB  - The antidiabetic agent troglitazone (CS-045) and a metabolite designated M3 have
      potent blood glucose-lowering actions. The mechanism of the hypoglycemic effects
      of troglitazone and M3 was investigated in cultured L6 muscle cells. Short-term
      (2-hour) exposure of fully differentiated myotubes to troglitazone had no effect
      on glucose transport activity; M3 exposure caused a modest (50% to 60%) increase
      in basal and insulin-stimulated transport. Long-term (72-hour) treatment of
      myotubes with troglitazone resulted in a doubling of glucose transport in the
      absence of insulin, whereas M3 treatment resulted in a fivefold increase in basal
      glucose transport. Transport activity in M3-treated myotubes was greater than
      that seen after short-term insulin treatment. Insulin did not stimulate transport
      further in long-term M3-treated cells. A similar effect of prolonged exposure to
      M3 was observed in nondifferentiated myocytes. The agent had no influence on cell
      growth or the extent of differentiation. Augmentation of basal glucose transport
      by M3 was slow in onset, requiring 18 to 24 hours before significant effects were
      observed and 72 hours for full stimulation. M3 action on glucose transport was
      also dose-dependent, with half-maximal stimulation at 5 micrograms/mL of the
      agent and full effects at 10 to 20 micrograms/mL. Total membranes were prepared
      from control and M3-treated L6 myocytes and myotubes, and glucose transporter
      (GLUT1 and GLUT4) protein levels were measured by Western blotting. GLUT1 content
      was increased 2.9- +/- 1.3- and 2.8- +/- .2-fold by M3 treatment in myocytes and
      myotubes, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7637658
TI  - Moexipril: another ACE inhibitor for hypertension.

PMID- 7637657
TI  - Elevated plasma ceruloplasmin in insulin-dependent diabetes mellitus: evidence
      for increased oxidative stress as a variable complication.
AB  - Ceruloplasmin (Cp) is an acute-phase-responsive oxidase enzyme. Prior reports
      suggest that Cp is increased in diabetes mellitus, perhaps reflecting greater
      oxidant stress. However, the situation in insulin-dependent diabetes mellitus
      (IDDM) per se remains unclear. Furthermore, vitamin C can interfere with one
      indirect assay for Cp, and vitamin C metabolism is altered in IDDM. We measured
      Cp levels by both a direct radial immunodiffusion (RID) assay and an indirect
      oxidase assay in 10 subjects with IDDM and 10 nondiabetics, both at baseline and
      after 30 days of vitamin C supplementation (100 or 600 mg daily, five subjects
      per group). Plasma copper level was measured independently also. Our data show
      that circulating levels of Cp are significantly increased in IDDM subjects as a
      group, and specifically that Cp is abnormally high in a subset of IDDM
      individuals. Vitamin C supplementation at either dose interfered with the oxidase
      assay for Cp in both groups, but vitamin C did not alter the RID assay. The
      observed increase in plasma copper suggests that circulating holo-Cp is
      increased. The finding of increased Cp in some individuals with IDDM supports the
      hypothesis of increased oxidant stress as a variable factor in the spectrum of
      chronic complications in diabetes. Measurements of Cp level by the oxidase assay
      must be considered unreliable for subjects taking vitamin C supplements of > or =
      100 mg/d.

PMID- 7637659
TI  - A topical carbonic anhydrase inhibitor for glaucoma.

PMID- 7637656
TI  - Insulin resistance in adipocytes of obese women: effects of body fat distribution
      and race.
AB  - Upper-body obesity (UBO) in white women is associated with increased fatty acid
      turnover and resistance to the effects of insulin on systemic glucose metabolism.
      The present study determined whether the abilities of insulin to stimulate
      glucose transport and suppress lipolysis are impaired in adipocytes from white
      UBO (W-UBO) women. Because the clinical risks associated with UBO are attenuated
      in black women, the effects of race on adipocyte insulin sensitivity were
      assessed. Forty-two healthy, equally obese women were selected for study on the
      basis of race (black or white) and body fat distribution (UBO or lower-body
      obesity [LBO]). In white women, both abdominal and gluteal fat cells from the UBO
      versus LBO group were less responsive to the stimulatory effects of insulin on
      glucose uptake and less sensitive to the antilipolytic effects of insulin and the
      adenosine analog, phenylisopropyladenosine (PIA). In contrast, in black women,
      fat cells from UBO and LBO groups were equally sensitive to the stimulatory
      effects of insulin on glucose transport and the suppressive effects of insulin
      and PIA on lipolysis. These in vitro data correlate well with previous clinical
      findings that UBO in white women but not in black women is associated with
      insulin resistance and dyslipidemia. Thus, resistance to the antilipolytic
      effects of insulin and adenosine at the level of adipose tissue may increase
      systemic lipolysis and play a role in the development or maintenance of
      peripheral insulin resistance associated with UBO in white women, but not in
      black women.

PMID- 7637660
TI  - Influenza vaccine, 1995-1996.

PMID- 7637661
TI  - International Society of Pediatric Oncology, SIOP XXVII meeting. Montevideo,
      Uruguay, October 10-14, 1995. Abstracts.

PMID- 7637662
TI  - [Guidelines for equipment needs in home ventilation. Home and Long-term
      Ventilation Study Group].

PMID- 7637664
TI  - [Predictive factors of minimally effective nCPAP ventilation in treatment of
      obstructive sleep apnea?].
AB  - BACKGROUND: Nasally applied continuous positive airways pressure (nCPAP)
      ventilation is an effective treatment of obstructive sleep apnoea syndrome
      (OSAS). As the lowest effective nCPAP-level (nCPAPmin) inter-individually is
      quite variable individual pressure titration under polysomnographic monitoring is
      necessary. AIM: To determine whether nCPAPmin can reliably be predicted on the
      basis of clinical and polysomnographic variables. PATIENTS AND METHODS: A set of
      77 unselected OSAS-patients was investigated in the sleep laboratory. We used a
      standard sleep-related questionnaire, examined anthropometric variables,
      performed lung function tests and blood gas analyses, and measured nasal cross
      sectional area as well as nasal flow resistance. In the night prior to the nCPAP
      titration a cardiorespiratory polygraphy was performed. Stepwise multiple
      regression analysis using the titrated nCPAPmin as dependent variable and the
      clinical and polygraphic data as independent variables revealed gender (GES),
      neck circumference (NCF), body mass index (BMI), and apnoea-/hypopnea index (AHI)
      as the optimal set of predictors of nCPAPmin in this model. RESULTS: Multiple
      regression analysis with these factors yielded the following equation: predicted
      nCPAPmin = 1.95 + 0.80 x GES + 0.09 x BMI + 0.01 x NCF + 0.03 x AHI (woman: GES =
      1; man: GES = 2). The reliability of the equation was tested with a second set of
      180 prospective OSAS-patients. In these patients the mean nCPAP-level as titrated
      in the sleep laboratory was 9.1 +/- 2.0 mbar, whereas the mean predicted nCPAP
      level was 8.4 +/- 3.6 mbar (p = n.s.). In 51% of the patients the difference
      between nCPAPmin measured and predicted was greater than +/- 1 mbar. CONCLUSION:
      This equation is neither sufficient to reliably predict nCPAPmin nor to prescribe
      nCPAP without individual pressure titration. The calculated nCPAP-level might
      however contribute to choosing the most suitable flow generator prior to the
      titration night.

PMID- 7637663
TI  - [Goiter incidence in Germany is greater than previously suspected].
AB  - BACKGROUND: The data regarding goitre prevalence in Germany is based on
      calculation arising out of dissimilar studies conducted among inhomogeneous study
      groups. The aim of our study was to collect data towards prevalence of goitre,
      thyroid size and structure through a prospective nationwide survey conducted
      using identical examination methods and study protocol. PATIENTS AND METHOD: A
      total number of 6815 subjects belonging to various age groups and spread over 32
      regions in Germany participated in our thyroid ultrasound study conducted with a
      7.5 MHz transducer. Information regarding nutrition, use of iodised table salt
      and iodine containing medicine and/or substances were collected through a
      questionnaire. The volumetry and age related normal values were followed as per
      the guidelines set by Deutsche Gesellschaft fur Endokrinologie. RESULTS: Enlarged
      thyroid was seen in 50% of 18 to 70 year age group, 52% of 11 to 17 year age
      group and in 21% of children up to 10 years. Focal lesions were detected in 2.5%
      of subjects below 18 years and in 30% of women and 21% of men over 18 years. A
      positive correlation between age, thyroid volume and number of thyroid nodules
      was seen. Up to 83% of the examined subjects admitted to using iodised table
      salt. Children consuming iodised salt were found to have smaller thyroid glands.
      No correlation was found between the consumption of iodised salt and thyroid size
      in the adolescent age group and young adults. CONCLUSION: The prevalence of
      goitre in Germany is higher than it has been reported. The study underlines the
      insufficiency of the present goitre prophylaxis. Only an iodine prophylaxis
      (table salt, food products, fodder) backed by legislative measures can bring
      about a real breakthrough.

PMID- 7637665
TI  - [Thoracopulmonary actinomycosis, a difficult differential diagnosis in suspected
      tumor].

PMID- 7637666
TI  - ['95 pneumology update. Progress and perspectives in pneumology. Paradigms of
      change (II)].

PMID- 7637667
TI  - [Inhalation damage to the lung caused by environmental and occupational
      exposure].

PMID- 7637668
TI  - [Methotrexate therapy of inflammatory diseases. Reliable effects and recent
      developments in rheumatology, pneumology, gastroenterology and dermatology].

PMID- 7637669
TI  - [Alternative medicine--belief in the unbelievable?].

PMID- 7637671
TI  - Donn's perspective on workplace issues.

PMID- 7637672
TI  - Disabilities among children aged < or = 17 years--United States, 1991-1992.
AB  - Disabilities among children result in substantial reductions in quality of life
      and are associated with increased dependence on the health-care and social
      service systems. To assess the prevalence of disabilities and their associated
      health conditions children, CDC reviewed data from the Survey of Income and
      Program Participation (SIPP) for 1991-1992, which collected information about
      chronic conditions, including the functional limitations related to those
      conditions (1,2). This report summarizes SIPP data for children aged < or = 17
      years.

PMID- 7637670
TI  - [Adult-onset Still's disease].

PMID- 7637673
TI  - State and national vaccination coverage levels among children aged 19-35 months-
      United States, April-December 1994.
AB  - The National Immunization Survey (NIS) is a single survey providing state and
      national estimates of vaccination coverage levels among children aged 19-35
      months. CDC implemented the NIS in April 1994 as one element of the five-part
      Childhood Immunization Initiative (CII) (1), a national strategy to achieve and
      maintain high vaccination levels among children during the first 2 years of life.
      NIS collects quarterly data from the 50 states, the District of Columbia, and 27
      urban areas considered to have populations at high risk for undervaccination.
      This report of initial NIS findings provides the results of both national and
      state vaccination coverage levels for April-December 1994.

PMID- 7637674
TI  - Mumps surveillance--United States, 1988-1993.
AB  - PROBLEM/CONDITION: CDC monitors the incidence of mumps in the United States
      through the passive reporting of cases to its National Notifiable Disease
      Surveillance System (NNDSS). REPORTING PERIOD COVERED: 1988-1993. DESCRIPTION OF
      SYSTEM: Weekly reports to the NNDSS from 48 states and the District of Columbia
      were used to calculate incidence rates for mumps. State immunization requirements
      were obtained from the U.S. Department of Health and Human Services. RESULTS:
      After the licensure of mumps vaccine in the United States in December 1967 and
      the subsequent introduction of state immunization laws in an increasing number of
      states, the reported incidence of mumps decreased substantially. The 1,692 cases
      of mumps reported for 1993 represent the lowest number of cases ever reported to
      NNDSS and a 99% decrease from the 152,209 cases reported for 1968. During 1988
      1993, most cases occurred in children 5-14 years of age (52%) and in persons > or
      = 15 years of age (36%). Although the incidence decreased in all age groups, the
      largest decreases (> 50% reduction in incidence rate per 100,000 population)
      occurred in persons > or = 10 years of age. Overall, the incidence of mumps was
      lowest in states that had comprehensive school immunization laws requiring mumps
      vaccination and highest in states that did not have such requirements.
      INTERPRETATION: Because of the extensive use of mumps vaccine and the increased
      number of states that had enacted mumps immunization laws, the number of reported
      mumps cases decreased further since the marked decline that began during the
      early 1970s. The earlier shift in incidence from children of school ages to older
      persons that was noted during 1985-1988 continued until 1992, when the proportion
      of cases occurring in children of school ages increased and exceeded the
      proportions occurring in other age groups. ACTIONS TAKEN: All health-care
      providers are encouraged to a) report mumps cases to their local and state health
      departments for transmission to NNDSS and b) enact school immunization laws
      requiring mumps vaccination.

PMID- 7637676
TI  - Frequency of Trichophyton rubrum in tinea capitis.
AB  - Trichophyton rubrum has led to unprecedented worldwide suppression of other
      dermatophytes which had been predominant earlier as a causative agent of
      superficial dermatomycoses. In tinea capitis on the other hand, several other
      species of Trichophyton or Microsporum are dominant depending on the region or
      continent. Tinea capitis caused by T. rubrum is a rare event worldwide.
      Occasional concentrations may be explained by several cases occurring by chance
      in one family or community. The relative frequency of this causative agent in
      tinea capitis in children is under 1%. In adults, however, where tinea capitis
      occurs very infrequently indeed, the incidence of T. rubrum appears to exceed
      10%. Apart from two studies from India, one from Iran, two from Portugal and
      observations from Germany, which in the first country report of around 30% of all
      cases published, while the others document some 10% each, there are not only any
      conspicuous, unequivocal concentrations at all. Increased frequency of T. rubrum
      in this clinical picture has not been easily recognizable over the last decades
      due to low absolute case numbers.

PMID- 7637677
TI  - Fine structural investigation of Malassezia furfur. II. The envelope of the yeast
      cells.
AB  - The general ultrastructure of the Malassezia furfur cell envelope is shown in a
      schematic model. Distinct layers such as the outer lamella, the cell wall and the
      plasma membrane and special structural elements of the cell wall are described
      and presented in electronmicrographs. Special attention was paid to the outer
      lamellar layer that seems to be equivalent to a capsule. It probably contains
      lipids as well as the cell wall, and it seems to participate in attachment
      processes.

PMID- 7637675
TI  - Surveillance for anencephaly and spina bifida and the impact of prenatal
      diagnosis--United States, 1985-1994.
AB  - PROBLEM/CONDITION: The reported prevalence of anencephaly and spina bifida in the
      United States has steadily declined since the late 1960s. During this time, the
      ability to diagnose these defects prenatally has progressed rapidly. Many U.S.
      birth defects surveillance systems ascertain defects only among live-born infants
      or among infants and fetuses beyond a certain gestational age, thus excluding
      defects among pregnancies prenatally diagnosed as being affected by a neural tube
      defect (NTD) and electively terminated before the gestational age limit. The
      impact of prenatal diagnosis and subsequent pregnancy termination on the reported
      prevalence of anencephaly and spina bifida in the United States has not been well
      established. However, assessment of this impact is crucial to the use of
      surveillance data to monitor trends in the occurrence of NTDs and the
      effectiveness of interventions for these defects (e.g., increased consumption of
      folic acid). REPORTING PERIOD: This report presents data from birth defects
      surveillance systems in six states over different time periods: Arkansas, 1985
      1989; California, 1989-1991; Georgia, 1990-1991; Hawaii, 1988-1994; Iowa, 1985
      1990; and South Carolina, 1992-1993. DESCRIPTION OF SYSTEMS: Population-based
      data about a) live-born and stillborn infants with anencephaly and spina bifida
      and b) pregnancies electively terminated after prenatal diagnosis of these
      defects were analyzed from the Arkansas Reproductive Health Monitoring System;
      the California Birth Defects Monitoring Program; CDC's Metropolitan Atlanta
      Congenital Defects Program; the Iowa Birth Defects Registry, the University of
      Iowa, and the Iowa Department of Public Health; and the Greenwood Genetic Center
      in South Carolina. Data also were analyzed from the Hawaii Birth Defects
      Monitoring Program, which includes data for some women who were not residents of
      the state. The systems differed in the size and racial/ethnic composition of the
      populations studied, the surveillance methods used, the completeness of
      ascertainment, and the availability and utilization of prenatal testing and
      pregnancy termination. RESULTS AND INTERPRETATION: Among all pregnancies
      ascertained in which the infant or fetus had anencephaly or spina bifida, the
      percentages that were electively terminated ranged from 9% in Arkansas to 42% in
      Atlanta and Hawaii, with a corresponding increase in the adjusted prevalence of
      these defects compared with the prevalence at birth. In each system, pregnancies
      associated with anencephaly were terminated more frequently than were those
      associated with spina bifida. These data indicate that the impact of prenatal
      diagnosis and subsequent pregnancy termination on the prevalence at birth of
      anencephaly and spina bifida differs among geographic areas and populations.
      Comprehensive surveillance for these defects requires inclusion of pregnancies
      that are prenatally diagnosed and then terminated. ACTIONS TAKEN: CDC will use
      these data to promote the inclusion of prenatally diagnosed and terminated
      pregnancies in estimates of the prevalence of anencephaly and spina bifida
      generated by birth defects surveillance programs in the United States. Including
      such pregnancies is crucial to the ability of these programs to monitor trends
      accurately and to establish the effectiveness of interventions, including the use
      of folic acid, for these defects.

PMID- 7637678
TI  - Growth inhibition of Malassezia species by pharmacological concentrations of
      polidocanol.
AB  - In vitro antifungal properties of polidocanol (Thesi), a hydroxypolyethoxydecan,
      were investigated against various yeasts at concentrations of 0.05-10% (w/w) by
      means of the agar diffusion test; in the case of lipophilic Malassezia furfur,
      polidocanol-containing olive oil was used additionally for sensitivity study. Six
      strains of M. furfur of different clinical origin were tested as well as strains
      of C. albicans (3), C. krusei (3), C. parapsilosis (2), C. robusta (2), Tr.
      cutaneum (2) and one strain each of C. guilliermondii, C. glabrata, C. tropicalis
      and M. pachydermatis. Both test systems revealed predominantly fungistatic
      activity against M. furfur, with a minimal inhibitory concentration (MIC) of 1%
      polidocanol (w/w), while yeasts of other genera (Candida species, Trichosporum
      species) showed no or only transitory (C. krusei) inhibition of growth. M.
      pachydermatis was also found to be sensitive with a MIC of 0.1%; this suggests a
      specific inhibitory effect against the genus Malassezia. Polidocanol, which has
      been used for decades as an antipruritic and analgesic in various topical
      preparations at concentrations between 3% and 5%, might therefore be suitable for
      prophylaxis of recurrent pityriasis versicolor or in veterinary medicine.

PMID- 7637679
TI  - Validity of contour-clamped homogeneous electric field electrophoresis as a
      typing system for Candida albicans.
AB  - Instigated by an increase in serious human Candida infections and aided by
      advances in technology, there has been renewed interest in the study of the
      epidemiology of fungal infections. Among the newer techniques available, contour
      clamped homogeneous electric field (CHEF) electrophoresis has shown great promise
      as a tool for typing strains of Candida albicans. However, few studies have
      addressed the reproducibility of the preparatory and electrophoretic methods.
      Through a series of analyses on clinical isolates of C. albicans, we were able to
      demonstrate that (a) sample preparation induced no appreciable artifacts in CHEF
      banding patterns; (b) the electrophoretic patterns were reproducible over time;
      (c) changes in colony morphology were not associated with changes in the
      electrophoretic pattern, and (d) the method was more sensitive than restriction
      enzyme analysis (REA) for demonstrating strain differences. CHEF electrophoresis
      is a sensitive and reproducible tool for the study of Candida epidemiology.
      Further use and study of this methodology is warranted.

PMID- 7637680
TI  - Discrimination of strains of Candida albicans isolated from deep and superficial
      sites by resistotyping.
AB  - Resistotyping was used to characterise 106 strains of Candida albicans classified
      as to whether they came from deep or superficial infections. The data were
      analysed by logistic regression analysis. There was a statistically significant
      difference between the two groups of strains. After removal of variables by the
      log-likelihood method four resistotyping agents were found to predict source of
      strain: boric acid, benzalkonium chloride, malachite green and mercurochrome.
      Whilst there were phenotypic differences between strains isolated from deep and
      superficial sites it is not clear whether this strain represents different strain
      types or strain histories.

PMID- 7637681
TI  - Orointestinal yeast colonization of paediatric oncologic patients during
      antifungal prophylaxis: results of quantitative culture and Candida serology and
      comparison of three polyenes.
AB  - The orointestinal yeast colonization of 46 children with newly diagnosed
      malignancies was studied prospectively and longitudinally with quantitative
      cultures during remission induction chemotherapy. The initial colonization rate
      was 24%; only 28% of the patients remained free of yeasts during their entire
      treatment although all of them continuously received oral polyenes as antifungal
      prophylaxis. A randomized comparison of natamycin (suspension, lozenges),
      nystatin (suspension) and amphotericin B (suspension, lozenges) failed due to
      serious problems with patient compliance. Natamycin was best accepted by the
      patients and natamycin lozenges were the most efficacious drug in the oral
      cavity. The effectivity of the suspensions of nystatin and amphotericin B was
      similar; both were equally efficacious in the oral cavity and the gut. Assessment
      of faecal polyene concentrations by HPLC showed the highest results for
      amphotericin B (mean 6808 microgram(-1)). Regularly performed Candida serology
      (indirect haemagglutination, indirect immunofluorescence and immunodiffusion
      precipitation) revealed significant titre increases in 63% of the patients. In
      six cases, the synopsis of clinical picture, culture and serology strongly
      suggested systemic yeast invasion.

PMID- 7637682
TI  - Orointestinal yeast colonization of paediatric bone marrow transplant recipients:
      surveillance by quantitative culture and serology.
AB  - We quantitatively studied the orointestinal yeast colonization of 15 consecutive
      paediatric patients who underwent 16 bone marrow transplantations (BMT). Cultures
      were performed initially, longitudinally weekly during the period of aplasia (in
      patient treatment) and, if possible, also during out-patient follow-up. With one
      exception, all patients received fluconazole as antifungal prophylaxis. Patients
      remained free of yeasts during the complete observation period only in six out of
      16 cases (38%). Non-albicans species of Candida were isolated in six out of 16
      cases (38%), mainly C. glabrata (five out of 16; 31%). All of these patients had
      undergone allogeneic BMT. In one case, there was indirect evidence of systemic
      invasion by C. glabrata. Even combined prophylaxis with fluconazole and and
      amphotericin B suspension could not reliably prevent yeast colonization but this
      combination at present appears to be the optimal regime. Regular concomitant
      Candida serology (determination of specific antibodies by three methods) proved
      to be a valuable additional surveillance method.

PMID- 7637683
TI  - In vitro susceptibility of Candida species isolated from patients with
      haematological malignancies.
AB  - Candida spp. (83 isolates including C. (Torulopsis) glabrata) were tested in
      vitro for their susceptibility to 5-fluorocytosine, amphotericin B, ketoconazole,
      itraconazole, fluconazole, and miconazole. The yeasts were isolated from clinical
      specimens, mostly from the lower respiratory tract, of 30 oncologic patients,
      27/30 with haematological malignancies, during a 6-month period (December 1991
      May 1992). Minimal inhibitory concentration (MIC) and minimal fungicidal
      concentration (MFC) values of the 6 drugs were obtained for each yeast using a
      microdilution broth method developed in our laboratory. Amphotericin B, and 5
      fluorocytosine were active against the majority of the yeasts with MIC90/MFC90
      values within achievable serum concentrations (3.12/6.25 micrograms ml(-1) and
      0.625/0.625 micrograms ml(-1) respectively). Azole derivatives showed a species
      specific activity. MFC values were two to four times higher than those of the
      MICs, confirming the fungistatic rather than fungicidal activity of azole
      derivatives. An interesting correlation was found when the in vitro
      susceptibility values of the isolates were compared with data of patients with or
      without antifungal prophylaxis or therapy during that period. In general, with
      respect to fluconazole, C. albicans strains isolated from patients who received
      no treatment showed MIC and MFC values lower than those obtained from patients
      who were under prophylaxis or treatment with this drug. Fluconazole
      administration appears to influence in vitro susceptibility testing.

PMID- 7637685
TI  - Pyoderma gangraenosum caused by Rhizopus arrhizus.
AB  - A rare case of pyoderma gangraenosum caused by Rhizopus arrhizus is reported. The
      patient, a 50-year-old male farmer, was admitted to hospital complaining of
      gangrening and festering of the right upper arm with severe pain for nearly 2
      months. A lesion was found on the inside of right upper arm. The central skin
      part of the lesion became black dry gangrenous, the periphery was deeply
      ulcerated with yellow-green pus. The necrotic crust, biceps, triceps and vessels
      inherited a histopathologically proven fungal infection. The fungus isolated was
      identified as Rhizopus arrhizus. The infection was successfully treated with
      itraconazole.

PMID- 7637684
TI  - Hyalohyphomycoses due to Fusarium spp.--two case reports and review of the
      literature.
AB  - We report a case of a severe Fusarium solani keratitis in a 82-year-old patient
      with a history of surgical trauma. Antimycotic therapy and keratoplasty led to
      markedly improved vision. Identification of the fungus was complicated by the
      fact that the isolate did not produce the typical macroconidia. The second case
      was a fatal disseminated Fusarium verticillioides infection in a 69-year-old
      patient during neutropenia after chemotherapy of acute myelogenous leukemia. The
      patient developed pneumonia, fever, skin lesions, myalgia, and fungaemia. The
      clinical signs, diagnosis and therapy of localized and disseminated Fusarium
      infections are outlined and discussed in view of the literature.

PMID- 7637686
TI  - Successful treatment of chromoblastomycosis with itraconazole.
AB  - An unusual severe case of chromoblastomycosis due to Cladosporium carrionii
      unresponsive to 5-FC and some azoles is reported. With oral itraconazole at a
      dosage of 100 mg d(-1) for 15 months (total dose 45.5 g) the patient had a
      complete clinical and mycological recovery without any side-effects.

PMID- 7637687
TI  - Studies of the influence of ochratoxin A on immune and defense reactions in the
      mouse model.
AB  - In the mouse model, the mycotoxin ochratoxin A has a non-selective suppressive
      effect on various immune and defence reactions. Apart from weight depression,
      lymphopenia, neutrophilia and eosinophilia, antibody-producing cells, antibody
      titres in blood serum and phagocytosis of Escherichia coli by blood phagocytes
      become suppressed. Moreover, immunized animals show a lower survival rate after
      experimental infection with Pasteurella multocida as well as an increase in
      oxygen radicals in blood cells.

PMID- 7637688
TI  - Trichophyton rubrum as the causative agent of tinea capitis in three children.
AB  - Tinea capitis, which is caused by Trichophyton rubrum, is only rarely described
      in medical literature. Incidence of this disease appears to lie well below 1% in
      Europe. Microsporum canis, Trichophyton mentagrophytes and Trichophyton tonsurans
      are the predominant causative agents discussed here. In April 1993 T. rubrum was
      isolated from typical pathological changes to the capillitium area in three
      children from a Nigerian family, who had been living in Germany for 3 years. All
      three children revealed multiple, round or irregularly formed, partially
      infiltrated, partially pustular, hairless areas measuring up to 2 cm in diameter
      and covered with tightly clinging scales. The children's parents did not suffer
      from any dermatological complaints. The oldest child had had these pathological
      changes for about 5 months, the other two for a shorter length of time. Therapy
      with 10 mg kg(-1) body weight of griseofulvin led to rapid recovery over a period
      of 4 weeks.

PMID- 7637689
TI  - Inhibition of growth and mycotoxin production of Alternaria alternata inhabiting
      decayed fruits by pesticides.
AB  - The effect of the two pesticides, cuprosan and sumi oil, on growth and mycotoxin
      production by two strains of Alternaria alternata isolated from decayed fruits
      was studied. Mycelial biomass of the two strains was significantly inhibited with
      most applied doses, however, cuprosan was most effective. Sumi oil exhibited
      significant inhibitory effect on the Alternaria strain isolated from decayed
      lemons, whereas, it suppressed mycelial biomass of that isolated from decayed
      tomatoes at only higher doses (250 ppm). Mycelial respiration of the two tested
      strains was mainly inhibited by most used does. However, CO2 evolution was
      occasionally promoted. Synthesis of alternariol (AOH) and its monomethyl ether
      (AME) by the examined strains was mainly inhibited by pesticide application in a
      manner similar to that of mycelial growth.

PMID- 7637690
TI  - Parasitism and chromosome dynamics in protozoan parasites: is there a connection?
AB  - Genomic plasticity is a hallmark of many protozoan parasites, including
      Plasmodium spp, Trypanosoma spp, Leishmania ssp and Giardia lamblia. Strikingly,
      there is a common theme regarding the structural basis of this karyotype
      variability. Chromosomes are compartmentalized into conserved central domains and
      polymorphic chromosome ends. Since antigen-encoding genes frequently reside in
      telomere-proximal domains, it is tempting to speculate that the genetic
      flexibility of chromosome ends has been recruited as a tool in immune evasion
      strategies by some parasitic protozoa.

PMID- 7637691
TI  - A member of the ClpB family of stress proteins is expressed during heat shock in
      Leishmania spp.
AB  - We have identified and isolated the Leishmania major homologue to the bacterial
      ClpB gene and to the yeast Hsp104 gene. ClpB in Leishmania major is a single-copy
      gene and encodes a low-abundance mRNA which is induced several-fold during a heat
      stress. We raised antibodies against the product of the recombinant gene and show
      that the leishmanial ClpB encodes a predominantly cytoplasmic protein of approx.
      100 kDa which is detectable in Leishmania promastigotes of various species after
      exposure to elevated temperatures. We, therefore, term this protein Hsp100.

PMID- 7637692
TI  - Purification and characterization of a soluble nucleoside diphosphate kinase in
      Trypanosoma cruzi.
AB  - A soluble nucleoside diphosphate kinase (NDP kinase) was purified and
      characterized in epimastigote forms of Trypanosoma cruzi. The enzyme was purified
      by affinity chromatography on Blue-agarose and Q-Sepharose columns and by FPLC on
      a Superose 12 column. A membrane-associated NDP kinase was identified which
      accounts for 30% of total enzymatic activity. Western blot analysis of the
      soluble NDP kinase revealed a 16.5-kDa monomer recognized by polyclonal
      antibodies to NDP kinase from Dictyostelium discoideum, Candida albicans or
      human. Most of the T. cruzi NDP kinase is found in the cell as a hexamer composed
      of 16.5-kDa monomers. The Km values of the enzyme for ATP, GDP and dTDP were 0.2
      +/- 0.008 mM, 0.125 +/- 0.012 mM and 0.4 +/- 0.009 mM, respectively. The parasite
      enzyme was stable, remained active at 65 degrees C and was found to tolerate up
      to 2.5 M urea. The 16.5-kDa subunit was phosphorylated with [gamma-32P]ATP or
      thiophosphorylated with [35S]GTP gamma S. The incubation of the 32P-labelled
      phosphoenzyme with unlabelled nucleoside 5'-diphosphates resulted in the
      formation of 32P-labelled nucleoside 5'-triphosphates without strict base
      specificity, indicating that the reaction mechanism of the T. cruzi enzyme is the
      same as reported for other NDP kinases. When the phosphoenzyme was incubated with
      a mixture of nucleoside 5'-diphosphates, GTP was preferentially formed.

PMID- 7637693
TI  - High-density-lipoprotein-independent killing of Trypanosoma brucei by human
      serum.
AB  - The cattle pathogen Trypanosoma brucei brucei is morphologically
      indistinguishable from the human pathogens T.b. rhodesiense and T.b. gambiense.
      However, unlike the human pathogens, T.b. brucei is lysed by normal human serum
      (NHS). The trypanolytic factor in NHS co-purifies with high-density lipoproteins
      (HDL), but its precise nature is unknown. Using a new fluorescence-based
      viability assay to assess T.b. brucei killing, we find that the HDL-deficient
      sera from two patients with Tangier disease are as trypanolytic as NHS.
      Fractionation of the Tangier sera by density ultracentrifugation revealed that
      the activity resides only in lipoprotein-depleted fractions. Tangier and NHS were
      also subjected to molecular sieving chromatography, and the activity profiles
      were identical. Lytic fractions to T. brucei (but not to T. rhodesiense) appeared
      under two distinct peaks of 100-600 kDa and > 1000 kDa. Neither peak coincided
      with the position of the major serum lipoproteins, as determined by cholesterol
      titrations. The high-molecular-mass peak did not contain the HDL-associated
      apolipoprotein-A1. Further, we did not find that purified apolipoproteins A1 or J
      are lytic for the trypanosomes. We conclude that the killing of T. brucei by
      human serum can be independent of HDL.

PMID- 7637695
TI  - Multiple genes code for high-molecular-mass rhoptry proteins of Plasmodium
      yoelii.
AB  - We have examined the number of genes coding for a group of high-molecular-mass
      rhoptry protein(s) in the malaria parasite Plasmodium yoelii, and studied
      variation in the gene family within the parasite's genome. A region of the genes
      was amplified using oligonucleotides based on conserved DNA sequences and the
      products cloned. The sequences could be divided into 7 groups by restriction
      fragment-length polymorphism. Further variation was detected by sequence
      analysis; 11 different sequences were detected in the 16 clones analyzed. The
      genes in the family were distributed on 6 chromosomes probably at 9 or more loci.

PMID- 7637694
TI  - Identification and characterization of myophilin, a muscle-specific antigen of
      Echinococcus granulosus.
AB  - A muscle-specific gene of Echinococcus granulosus has been identified and
      characterized. A lambda gt11 clone (10P1), containing an incomplete copy of the
      gene, was originally isolated from a larval E. granulosus cDNA library by serum
      antibodies from dogs infected with the parasite. The full-length cDNA sequence
      was obtained by PCR amplification of cDNA from an adult E. granulosus lambda
      gt22A library. Southern blot analysis indicated the presence of the gene as a
      single copy in the genome of E. granulosus and also detected homologous genes in
      genomic DNA of E. multilocularis and Taenia saginata. The 21.2-kDa protein
      deduced from the complete cDNA sequence contains two regions of 12 amino acids
      with similarity to the EF-hand motif of calcium binding proteins. Antibodies
      raised against the purified 10P1-GST fusion protein detected a 22-kDa antigen in
      the E. granulosus developmental stages examined. Immunoelectron microscopy
      localized the native protein in the muscle of the parasite. The amino-acid
      sequence of the E. granulosus protein shows significant homology to the muscle
      proteins mp20 of Drosophila melanogaster, chicken SM22 alpha and mammalian
      calponin, and also to the neuronal protein NP25 of rats. A conserved carboxy
      terminal motif of 17 amino acids is present in all the homologous proteins and is
      proposed to be the characteristic feature of a novel protein family. The term
      myophilin is proposed for the E. granulosus protein due to its localization and
      homology to other muscle proteins.

PMID- 7637696
TI  - A novel cultivation technique for long-term maintenance of bloodstream form
      trypanosomes in vitro.
AB  - We used an axenic cultivation system to grow African trypanosomes in vitro. Long
      term cultivation for more than 60 days has been achieved by replacing the culture
      medium at regular intervals between 6 and 48 h. In contrast to a control culture
      without medium replacement, increasing amounts of maximum cell concentrations
      have been obtained, ranging from 5 x 10(6) to 2 x 10(7) trypanosomes ml-1,
      whereas the generation doubling time remained constant (about 6 h). Higher cell
      concentrations have only been obtained by total medium replacement; neither
      addition of fresh medium nor serum led to a higher cell yield, suggesting that a
      trypanosome-derived factor or metabolite accumulated in the medium rather than
      medium was depleted of an essential nutrient. Most interestingly, however,
      successive waves have been obtained which eventually led to a damped oscillation
      curve with a constant high population density after about 40 days of cultivation.
      Cultures were started with a homogeneous population of the long-slender form. As
      judged by light microscopy, cells showed a stumpy morphology during the declining
      phase and became slender again in the following growth phase. At later time
      points, when cells remained in a stationary phase at high population density,
      many different morphological stages have been observed, similar to those
      described by early authors as intermediate forms [Ormerod, W. E. (1979) In:
      Biology of the Kinetoplastida, Vol. 2, pp. 340-393], although many dividing forms
      are still present at that time. In contrast, identically treated procyclic
      cultures were unable to produce cyclic growth waves. Based on these results, a
      novel concept considering a possible differentiation mechanism is discussed.

PMID- 7637697
TI  - Pfcrk-1, a developmentally regulated cdc2-related protein kinase of Plasmodium
      falciparum.
AB  - A gene encoding a novel cdc2-related protein kinase has been identified in
      Plasmodium falciparum, using degenerate oligonucleotides designed to hybridise to
      regions that are conserved in members of the cdc2 gene family. This gene, called
      Pfcrk-1, is located on chromosome 4. It is most closely related to the p58GTA
      gene family, members of which are negative regulators of cell growth in
      vertebrates. Pfcrk-1 is developmentally regulated, as indicated by stage-specific
      accumulation of mRNA in gametocytes.

PMID- 7637698
TI  - Isolation of a larval surface glycoprotein from Haemonchus contortus and its
      possible role in evading host immunity.

PMID- 7637699
TI  - Phylogenetic place of kinetoplastid protozoa inferred from a protein phylogeny of
      elongation factor 1 alpha.

PMID- 7637700
TI  - Identification of an Entamoeba histolytica gene encoding a protein homologous to
      prokaryotic disulphide oxidoreductases.

PMID- 7637701
TI  - Characterization of genes encoding members of the nuclear hormone receptor
      superfamily from Onchocerca volvulus.
AB  - Several lines of evidence suggest that molting in parasitic nematodes is
      controlled through the action of steroid molting hormones, or ecdysones. In other
      organisms, the central mediator of steroid hormone action is the hormone
      receptor. These receptor molecules are members of a superfamily of proteins
      called the nuclear hormone receptor family. Using an oligonucleotide derived from
      the amino-acid sequence of the Drosophila melanogaster ecdysone receptor, genes
      encoding homologues of the nuclear hormone receptor family were identified in the
      genome of the human filarial parasite Onchocerca volvulus. The O. volvulus genome
      contains at least three genes that encode putative members of the nuclear hormone
      receptor superfamily. A complete cDNA for one of these genes, designated OvNHR-1,
      has been isolated and characterized. The OvNHR-1 cDNA was 2378 bp in length, and
      contained a single open reading frame of 1104 bp. The open reading frame encoded
      a peptide with all of the features characteristic of a member of the nuclear
      hormone receptor superfamily of proteins. OVNHR-1 appeared to be encoded by a
      single-copy gene. Expression of the mRNA corresponding to OvNHR-1 was
      developmentally regulated, with maximal expression occurring during early
      embryogenesis. The polypeptide encoded by the OvNHR-1 open reading frame is
      antigenic in a minority of individuals exposed to O. volvulus.

PMID- 7637702
TI  - Amplification by polymerase chain reaction of Plasmodium falciparum DNA from
      Giemsa-stained thin blood smears.

PMID- 7637703
TI  - Trypanosoma cruzi heat-shock protein 90 can functionally complement yeast.

PMID- 7637705
TI  - Mitochondrial heat shock protein 70 is distributed throughout the mitochondrion
      in a dyskinetoplastic mutant of Trypanosoma brucei.

PMID- 7637704
TI  - A multitude of circular DNAs exist in the nucleus of Entamoeba histolytica.

PMID- 7637706
TI  - Isolation and sequences of cDNA clones for cytosolic and organellar hsp70 species
      in Eimeria spp.

PMID- 7637707
TI  - Dimorphism of the C terminus of the Plasmodium vivax merozoite surface protein 1.

PMID- 7637708
TI  - Molecular cloning of the cuticular collagen gene Bmcol-2 from Brugia malayi.

PMID- 7637709
TI  - The structural organization of an alpha 2 (type IV) basement membrane collagen
      gene from the filarial nematode Brugia malayi.

PMID- 7637710
TI  - Identification of Plasmodium falciparum histone 2B and histone 3 genes.

PMID- 7637711
TI  - The primary structure of a putative phosphatidylethanolamine-binding protein from
      Plasmodium falciparum.

PMID- 7637712
TI  - The construction of spliced leader cDNA libraries from the filarial nematode
      Brugia pahangi.

PMID- 7637713
TI  - Surface-associated serine-threonine kinase in Schistosoma mansoni.
AB  - Existing evidence suggests that parasites of the genus Schistosoma are responsive
      to external stimuli derived from the host and from parasites of the opposite sex.
      We hypothesize that these interactions are mediated by receptors at the parasite
      surface. To begin to address this issue, we have employed surface labelling by
      biotinylation to identify and isolate the surface molecules of adult S. mansoni.
      Isolated surface molecules were subsequently analyzed for the presence of protein
      kinases, since protein kinase activity is frequently associated with signal
      transducing receptors. Our results demonstrate that serine-threonine kinase
      activity is associated with the parasite surface and that surface proteins of
      145, 125, 95 and 57 kDa became phosphorylated on serine and threonine residues
      under in vitro conditions. No significant tyrosine phosphorylation of surface
      molecules was detected, despite the presence of many tyrosine-phosphorylated
      proteins in tegumental extracts. An additional unexpected finding of these
      studies was that adult schistosomes express considerably more surface molecules
      than previously indicated by radioiodination studies, and that the majority of
      these molecules are of parasite rather than host origin.

PMID- 7637714
TI  - Expression of GARP, a major surface glycoprotein of Trypanosoma congolense, on
      the surface of Trypanosoma brucei: characterization and use as a selectable
      marker.
AB  - Procyclic and epimastigote forms of Trypanosoma congolense express an
      immunodominant glutamic acid/alanine-rich protein (GARP) that covers the parasite
      surface. Although GARP shows no sequence similarity to procyclins from T. brucei,
      the general characteristics of the two sets of surface glycoproteins suggest that
      they have analogous functions, in much the same way that variant surface
      glycoproteins with unrelated primary sequences fulfil the same function in
      bloodstream form trypanosomes. Since T. brucei and T. congolense do not follow
      the same pathway through the tsetse fly, one possible function of procyclins
      might be to direct parasites to the correct compartments. As a first step towards
      testing this hypothesis, we have produced stably transformed procyclic forms of
      T. brucei in which the GARP coding region has been integrated into a procyclin
      expression site. GARP can be detected on the surface of these transgenic
      trypanosomes, uniformly distributed within the endogenous procyclin coat, but
      there are differences in post-translational modification when it is expressed in
      T. brucei rather than in T. congolense. The fact that GARP is readily accessible
      to antibodies which were raised against a bacterial fusion protein led us to
      examine its potential as a selectable surface marker for transfection. We have
      established a rapid and simple procedure for isolating stable transformants that
      provides an alternative to conventional methods of selection for antibiotic
      resistance.

PMID- 7637715
TI  - Toxoplasma gondii tachyzoites possess an unusual plasma membrane adenosine
      transporter.
AB  - Nucleoside transport may play a critical role in successful intracellular
      parasitism by Toxoplasma gondii. This protozoan is incapable of de novo purine
      synthesis, and must salvage purines from the host cell. We characterized purine
      transport by extracellular T. gondii tachyzoites, focusing on adenosine, the
      preferred salvage substrate. Although wild-type RH tachyzoites concentrated
      [3H]adenosine 1.8-fold within 30 s, approx. half of the [3H]adenosine was
      converted to nucleotide, consistent with the known high parasite adenosine kinase
      activity. Studies using an adenosine kinase deficient mutant confirmed that
      adenosine transport was non-concentrative. [14C]Inosine, [14C]hypoxanthine and
      [3H]adenine transport was also rapid and non-concentrative. Adenosine transport
      was inhibited by dipyridamole (IC50 approx. 0.7 microM), but not
      nitrobenzylthioinosine (15 microM). Transport of inosine, hypoxanthine and
      adenine was minimally inhibited by 10 microM dipyridamole, however. Competition
      experiments using unlabeled nucleosides and bases demonstrated distinct inhibitor
      profiles for [3H]adenosine and [14C]inosine transport. These results are most
      consistent with a single, dipyridamole-sensitive, adenosine transporter located
      in the T. gondii plasma membrane. Additional permeation pathways for inosine,
      hypoxanthine, adenine and other purines may also be present.

PMID- 7637716
TI  - Characterization of the lipid moiety of the glycosylphosphatidylinositol anchor
      of Trypanosoma cruzi 1G7-antigen.
AB  - The 90-kDa stage-specific 1G7-antigen has been implicated in the invasion of host
      cells by the metacyclic forms of Trypanosoma cruzi. The antigen is attached to
      the plasma membrane via glycosylphosphatidylinositol, the partial structure of
      which was the first to be determined for a protein of this parasite. In this
      study, the complete structure of the lipid component of the anchor was determined
      by electrospray mass spectrometry, gas chromatography mass spectrometry,
      phospholipase sensitivity and high-performance thin-layer chromatography of the
      diaradylglycerol components after benzoylation. These analyses showed that the
      lipid moiety of 1G7-antigen is composed essentially of 1-O-hexadecyl-2-O
      hexadecanoyl-phosphatidylinositol and 1-O-hexadecyl-2-O-octadecanoyl
      phosphatidylinositol. The high sensitivity of the electrospray mass spectrometric
      analysis unexpectedly revealed the presence of a small proportion of putative
      inositol-phosphoceramide structures, and confirmed the absence of inositol
      acylated species. An interesting finding was that the biosynthetic incorporation
      of [3H]palmitate labelled solely the acyl position, and not the 1-O-alkyl chain
      in the 1G7-antigen anchor.

PMID- 7637718
TI  - Trypanosoma cruzi trans-sialidase gene lacking C-terminal repeats and expressed
      in epimastigote forms.
AB  - Infective trypomastigote forms of Trypanosoma cruzi express an oligomeric trans
      sialidase that contains a long stretch of 12-amino-acid repeats at the C
      terminus, while the insect epimastigote forms having a monomeric trans-sialidase
      without repeats. Here we show that messenger RNAs encoding trans-sialidases
      containing the repeats are not present in epimastigotes but are abundant in
      trypomastigotes. In contrast, mRNA species encoding the conserved N-terminal
      domain are detected in epimastigotes. A cDNA clone derived from epimastigote mRNA
      was isolated and characterized. It predicts a repeat-minus amino-acid sequence
      that has 84% identity to the conserved N-terminal domain of trypomastigote trans
      sialidase, and contains some of the necessary amino acids for the catalytic
      activity, as shown by fusion experiments. Transcripts corresponding to this clone
      were detected in epimastigotes and in trypomastigotes by reverse-transcriptase
      and polymerase chain reaction. In addition, the lack of repeats is not due to RNA
      processing because the corresponding gene without repeats was amplified from the
      parasite DNA. These results suggest that a distinct set of genes encode the
      repeat-minus trans-sialidase, and only these trans-sialidase genes are expressed
      in epimastigote forms.

PMID- 7637717
TI  - Characterization of a dense granule antigen of Toxoplasma gondii (GRA6)
      associated to the network of the parasitophorous vacuole.
AB  - This work describes the molecular characterization of GRA6, a novel Toxoplasma
      gondii dense granule antigen of 32 kDa. cDNA clones encoding this protein were
      isolated using a rat serum directed against an HPLC fraction enriched in the
      protein GRA5. Cross-reactivity between GRA5 and GRA6 was demonstrated by
      production of sera against the recombinant GRA5 protein. A serum against a
      recombinant fragment of GRA6 which does not react with GRA5 allowed the
      localization of this antigen at the subcellular level. GRA6 is detected in the
      dense granules of tachyzoites, and in the parasitophorous vacuole, closely
      associated to the network. The gene encoding GRA6 and its flanking regions were
      completely sequenced from cDNA and genomic inserts. Primer extension experiments
      demonstrated that the cap site of the GRA6 gene was located 37 bp upstream of the
      5' end of the longest cDNA insert (1600 bp). The GRA6 gene potentially encodes a
      230-amino-acid polypeptide, does not contain any introns and seems to be present
      as a single copy in the genome of T. gondii. The deduced polypeptide contains two
      hydrophobic regions with the characteristics of transmembrane domains. The N
      terminal domain does not fit the classical feature of a signal peptide. The
      central hydrophobic domain is flanked by two hydrophilic domains which contain
      four blocks of amino acids homologous to the GRA5 protein. The C-terminal
      hydrophilic region comprises 24% of glycine residues, which may indicate a
      structural role for GRA6 in the network.

PMID- 7637719
TI  - Brugia spp. and Litomosoides carinii: identification of a covalently cross-linked
      microfilarial sheath matrix protein (shp2).
AB  - A microfilarial sheath protein gene (shp2) coding for the major constituent of
      the insoluble, cross-linked sheath remnant (SR) from Brugia malayi, Brugia
      pahangi and Litomosoides carinii has been cloned and sequenced, based on peptide
      partial amino-acid sequences. All three closely related single-copy shp2 genes in
      the two genera carry a single intron in identical position; shp2 mRNAs are post
      transcriptionally modified by both cis-splicing and trans-splicing. In accordance
      with their extracellular destinations the encoded proteins include signal peptide
      sequences; molecular masses of approx. 23 kDa are hence predicted for the mature
      secreted polypeptides. In their structures sheath matrix proteins shp2 may be
      regarded as extreme cases of a modular constitution, since these proteins largely
      consist of two different segments of multiple sequence repetitions, PAA and
      QYPQAP (or QYPQ), separated by elements of unique sequence. Extreme insolubility
      and cross-linking are likely to originate from these repetitive sequences within
      shp2, and to constitute the basic properties of a microfilarial matrix largely
      consisting of an shp2 network.

PMID- 7637720
TI  - Aspirin and the risk of colorectal cancer in women.
AB  - BACKGROUND: Most data suggest that the regular use of aspirin reduces the risk of
      colorectal cancer, but some apparently conflicting evidence exists. The effects
      of the dose and the duration of aspirin consumption on the risk of colorectal
      cancer are not well understood. METHODS: We determined rates of colorectal cancer
      according to the number of consecutive years of regular aspirin use (defined as
      two or more tablets per week) among women in the Nurses' Health Study who
      reported regular aspirin use on three consecutive questionnaires (1980, 1982, and
      1984) and compared the rates in this group with the rates among women who said
      they did not use aspirin. Cases of cancer occurring from 1984 through 1992 (the
      eight years after the 1984 questionnaire) were included. RESULTS: From 1984
      through 1992, we documented 331 new cases of colorectal cancer during 551,651
      person-years of follow-up. Women who consistently took two or more aspirin
      tablets per week had no appreciable reduction in the risk of colorectal cancer as
      compared with nonusers after four years (relative risk, 1.06; 95 percent
      confidence interval, 0.78 to 1.45) or after five to nine years (relative risk,
      0.84; 95 percent confidence interval, 0.55 to 1.28). There was a slight reduction
      in risk among women who took aspirin for 10 to 19 years, but it was not
      statistically significant (relative risk, 0.70; 95 percent confidence interval,
      0.41 to 1.20). However, there was a statistically significant reduction after 20
      years of consistent use of aspirin (relative risk, 0.56; 95 percent confidence
      interval, 0.36 to 0.90; P for trend = 0.008). The maximal reduction in risk was
      observed among women who took four to six tablets per week; higher doses had a
      similar apparent benefit. Controlling for risk factors for colorectal cancer,
      including diet, did not change the results, and the earlier diagnosis and removal
      of colorectal adenomas among aspirin users did not account for the results.
      CONCLUSIONS: Regular aspirin use, at doses similar to those recommended for the
      prevention of cardiovascular disease, substantially reduces the risk of
      colorectal cancer. However, this benefit may not be evident until after at least
      a decade of regular aspirin consumption.

PMID- 7637721
TI  - Oral ganciclovir as maintenance treatment for cytomegalovirus retinitis in
      patients with AIDS. Syntex Cooperative Oral Ganciclovir Study Group.
AB  - BACKGROUND: Cytomegalovirus retinitis, a sight-threatening infection associated
      with the acquired immunodeficiency syndrome (AIDS), currently requires lifelong
      intravenous treatment. An effective oral treatment would be an important advance.
      METHODS: We compared oral with intravenous ganciclovir in an open-label,
      randomized study in patients with AIDS and newly diagnosed, stable
      cytomegalovirus retinitis (the disease was stabilized by three weeks of treatment
      with intravenous ganciclovir). Sixty subjects were randomly assigned to
      maintenance therapy with intravenous ganciclovir at a dose of 5 mg per kilogram
      of body weight daily, and 63 to maintenance therapy with oral ganciclovir at a
      dose of 3000 mg daily. The subjects were followed for up to 20 weeks, with
      photography of the fundi conducted every other week. The photographs were
      evaluated at the completion of the study by an experienced grader who was unaware
      of the subjects' treatment assignments. RESULTS: Efficacy could be evaluated in
      117 subjects; photographs were ungradable for 2 of the 117. On the basis of the
      masked assessment of photographs from 115 subjects, the mean time to the
      progression of retinitis was 62 days in those given intravenous ganciclovir and
      57 days in those given oral ganciclovir (P = 0.63; relative risk [oral vs.
      intravenous], 1.08; 95 percent confidence interval for the difference in means, 
      22 to +12 days). On the basis of funduscopy by ophthalmologists who were aware of
      the subjects' treatment assignments, the mean time to progression was 96 days in
      subjects given intravenous ganciclovir and 68 days in subjects given oral
      ganciclovir (P = 0.03; relative risk [oral vs. intravenous], 1.68; 95 percent
      confidence interval for the difference in means, -45 to -11 days). Survival,
      changes in visual acuity, the incidence of viral shedding, and the incidence of
      adverse gastrointestinal events were similar in the two groups. Neutropenia,
      anemia, intravenous-catheter-related adverse events, and sepsis were more common
      in the group given intravenous ganciclovir. CONCLUSIONS: Oral ganciclovir is safe
      and effective as maintenance therapy for cytomegalovirus retinitis and is more
      convenient for patients to take than intravenous ganciclovir.

PMID- 7637722
TI  - Effect of pravastatin on outcomes after cardiac transplantation.
AB  - BACKGROUND: Hypercholesterolemia is common after cardiac transplantation and may
      contribute to the development of coronary vasculopathy. Pravastatin, a 3-hydroxy
      3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, has been shown to be
      effective and safe in lowering cholesterol levels after cardiac transplantation.
      Cell-culture studies using inhibitors of HMG-CoA reductase have suggested an
      immunosuppressive effect. METHODS: Early after transplantation, we randomly
      assigned consecutive patients to receive either pravastatin (47 patients) or no
      HMG-CoA reductase inhibitor (50 patients). RESULTS: Twelve months after
      transplantation, the pravastatin group had lower mean (+/- SD) cholesterol levels
      than the control group (193 +/- 36 vs. 248 +/- 49 mg per deciliter, P < 0.001),
      less frequent cardiac rejection accompanied by hemodynamic compromise (3 vs. 14
      patients, P = 0.005), better survival (94 percent vs. 78 percent, P = 0.025), and
      a lower incidence of coronary vasculopathy in the transplant as determined by
      angiography and at autopsy (3 vs. 10 patients, P = 0.049). There was no
      difference between the two groups in the incidence of mild or moderate episodes
      of cardiac rejection. In a subgroup of study patients, intracoronary ultrasound
      measurements at base line and one year after transplantation showed less
      progression in the pravastatin group in maximal intimal thickness (0.11 +/- 0.09
      mm, vs. 0.23 +/- 0.16 mm in the control group; P = 0.002) and in the intimal
      index (0.05 +/- 0.03 vs. 0.10 +/- 0.10, P = 0.031). In a subgroup of patients,
      the cytotoxicity of natural killer cells was lower in the pravastatin group than
      in the control group (9.8 percent vs. 22.2 percent specific lysis, P = 0.014).
      CONCLUSIONS: After cardiac transplantation, pravastatin had beneficial effects on
      cholesterol levels, the incidence of rejection causing hemodynamic compromise,
      one-year survival, and the incidence of coronary vasculopathy.

PMID- 7637723
TI  - Ketoconazole to reduce the need for cyclosporine after cardiac transplantation.
AB  - BACKGROUND: Because ketoconazole can markedly reduce the need for cyclosporine
      and because it also has antimicrobial properties, it may offer benefits in the
      treatment of patients after cardiac transplantation. METHODS: We randomly
      assigned 43 patients at the time of cardiac transplantation to receive
      ketoconazole (200 mg per day) (23 patients) or no ketoconazole (20 patients). The
      main end points were the dose of cyclosporine required and the incidence of
      cardiac rejection and infection. RESULTS: Ketoconazole reduced the dose of
      cyclosporine needed to maintain target levels by 62 percent at one week and by 80
      percent at one year. The cost savings per patient (in U.S. dollars, inclusive of
      the cost of ketoconazole) was about $5,200 in the first year and about $3,920 in
      each subsequent year. The mean (+/- SD) rate of rejection in the first month was
      lower in the ketoconazole group than in the controls (4.2 +/- 0.8 vs 5.7 +/- 1.0
      episodes per 100 patient-days, P < 0.001), and the average number of days to the
      first rejection was higher (30 +/- 29 vs. 15 +/- 8, P = 0.03). In the first year,
      22 percent of the ketoconazole group required cytolytic therapy, as compared with
      35 percent of the controls, and 9 percent of the ketoconazole group required
      total lymphoid irradiation, as compared with 15 percent of the controls (P =
      0.07). The incidence of infection was lower in ketoconazole-treated patients than
      in controls in the second month (1.4 +/- 0.5 vs. 2.8 +/- 0.7 episodes per 100
      patient-days, P < 0.001) and in the third month (0.8 +/- 0.3 vs. 2.3 +/- 0.6
      episodes per 100 patient days, P < 0.001). Transient, asymptomatic cholestasis
      was observed in the ketoconazole group. CONCLUSIONS: After cardiac
      transplantation, ketoconazole greatly reduced the need for cyclosporine,
      resulting in substantial cost savings. Ketoconazole also reduced the rates of
      rejection and infection, without persistent toxic effects. We now use
      ketoconazole routinely in cardiac-transplant recipients.

PMID- 7637724
TI  - Brief report: a duodenal gastrinoma in a patient with diarrhea and normal serum
      gastrin concentrations.

PMID- 7637725
TI  - Images in clinical medicine. Cytomegalovirus retinitis in AIDS.

PMID- 7637726
TI  - Seminars in medicine of the Beth Israel Hospital, Boston. Mitochondrial DNA and
      disease.

PMID- 7637727
TI  - Hunting for genes in computer data bases.

PMID- 7637728
TI  - Clinical problem-solving. Studying the classics.

PMID- 7637729
TI  - My years at the Journal--so far.

PMID- 7637730
TI  - Aspirin as prophylaxis against colorectal cancer.

PMID- 7637731
TI  - New therapies for cytomegalovirus retinitis.

PMID- 7637732
TI  - Recent advances in cardiac transplantation.

PMID- 7637733
TI  - Ataxia-telangiectasia--broad implications for a rare disorder.

PMID- 7637734
TI  - Rhabdomyolysis from the coadministration of lovastatin and the antifungal agent
      itraconazole.

PMID- 7637736
TI  - Thrombosis in the antiphospholipid-antibody syndrome.

PMID- 7637735
TI  - Thrombosis in the antiphospholipid-antibody syndrome.

PMID- 7637737
TI  - Thrombosis in the antiphospholipid-antibody syndrome.

PMID- 7637738
TI  - Thrombosis in the antiphospholipid-antibody syndrome.

PMID- 7637739
TI  - Thrombosis in the antiphospholipid-antibody syndrome.

PMID- 7637740
TI  - Immigrants and tuberculosis.

PMID- 7637741
TI  - Estrogen, lipid oxidation, and body fat.

PMID- 7637742
TI  - Cytomegalovirus retinitis and low CD4+ T-lymphocyte counts.

PMID- 7637743
TI  - Marijuana, the AIDS wasting syndrome, and the U.S. government.

PMID- 7637744
TI  - Body weight and mortality among women.
AB  - BACKGROUND: The relation between body weight and overall mortality remains
      controversial despite considerable investigation. METHODS: We examined the
      association between body-mass index (defined as the weight in kilograms divided
      by the square of the height in meters) and both overall mortality and mortality
      from specific causes in a cohort of 115,195 U.S. women enrolled in the
      prospective Nurses' Health Study. These women were 30 to 55 years of age and free
      of known cardiovascular disease and cancer in 1976. During 16 years of follow-up,
      we documented 4726 deaths, of which 881 were from cardiovascular disease, 2586
      from cancer, and 1259 from other causes. RESULTS: In analyses adjusted only for
      age, we observed a J-shaped relation between body-mass index and overall
      mortality. When women who had never smoked were examined separately, no increase
      in risk was observed among the leaner women, and a more direct relation between
      weight and mortality emerged (P for trend < 0.001). In multivariate analyses of
      women who had never smoked and had recently had stable weight, in which the first
      four years of follow-up were excluded, the relative risks of death from all
      causes for increasing categories of body-mass index were as follows: body-mass
      index < 19.0 (the reference category), relative risk = 1.0; 19.0 to 21.9,
      relative risk = 1.2; 22.0 to 24.9, relative risk = 1.2; 25.0 to 26.9, relative
      risk = 1.3; 27.0 to 28.9, relative risk = 1.6; 29.0 to 31.9, relative risk = 2.1;
      and > or = 32.0, relative risk = 2.2 (P for trend < 0.001). Among women with a
      body-mass index of 32.0 or higher who had never smoked, the relative risk of
      death from cardiovascular disease was 4.1 (95 percent confidence interval, 2.1 to
      7.7), and that of death from cancer was 2.1 (95 percent confidence interval, 1.4
      to 3.2), as compared with the risk among women with a body-mass index below 19.0.
      A weight gain of 10 kg (22 lb) or more since the age of 18 was associated with
      increased mortality in middle adulthood. CONCLUSIONS: Body weight and mortality
      from all causes were directly related among these middle-aged women. Lean women
      did not have excess mortality. The lowest mortality rate was observed among women
      who weighed at least 15 percent less than the U.S. average for women of similar
      age and among those whose weight had been stable since early adulthood.

PMID- 7637745
TI  - Association of weight loss and weight fluctuation with mortality among Japanese
      American men.
AB  - BACKGROUND: Weight loss and fluctuations in weight have been associated with
      increased risks of death from cardiovascular disease and from all causes. The
      clinical and public health implications of these associations are unclear.
      METHODS: We examined the long-term relation of weight change and fluctuation in
      weight with mortality over a 6-year period in 6537 middle-aged Japanese American
      men enrolled in the Honolulu Heart Program, a prospective study (mean follow-up,
      14.5 years). RESULTS: Men who had a weight loss of 4.5 kg or more or who had
      large fluctuations in weight (or both) over a six-year period were, on average,
      in poorer health than their peers whose weight was more stable. After the
      exclusion of subjects who died during the first five years of follow-up and after
      adjustment for confounding factors, a weight loss of more than 4.5 kg was
      associated with the risk of death from all causes, with the exception of death
      from cancer. The subjects whose weight fluctuated the most had a significantly
      higher risk of death from cardiovascular causes (relative risk, 1.41; 95 percent
      confidence interval, 1.03 to 1.93), death from noncardiovascular and noncancerous
      causes (relative risk, 1.53; 95 percent confidence interval, 1.12 to 2.10), and
      death from all causes (relative risk, 1.25; 95 percent confidence interval, 1.05
      to 1.48). However, the associations of weight loss and variation in weight with
      death from cardiovascular causes and from noncardiovascular and noncancerous
      causes were not found among healthy men who had never smoked. CONCLUSIONS: The
      associations between weight loss or fluctuation and mortality were partially
      explained by confounding factors and by the presence of preexisting disease.
      However, weight loss and weight fluctuation were unrelated to death among healthy
      men who had never smoked. Thus, concern about the health hazards of weight loss
      and variation may not be applicable to otherwise healthy people.

PMID- 7637746
TI  - Clonal proliferations of cells infected with Epstein-Barr virus in preinvasive
      lesions related to nasopharyngeal carcinoma.
AB  - BACKGROUND: The Epstein-Barr virus (EBV) is consistently detected in patients
      with nasopharyngeal carcinoma. To determine whether EBV infection is an early,
      initiating event in the development of this malignant tumor, we screened
      nasopharyngeal-biopsy samples, most of which were archival, for preinvasive
      lesions, including dysplasia and carcinoma in situ. Preinvasive lesions were
      found in 11 samples, which were tested for the presence of EBV. METHODS: EBV
      infection was detected with in situ hybridization for EBV-encoded RNAs (EBERs)
      and by immunohistochemical staining for latent membrane protein 1 (LMP-1). The
      larger samples were also tested for the EBV genome with the use of Southern
      blotting. The expression of specific EBV RNAs was determined by the amplification
      of complementary DNA with the polymerase chain reaction. RESULTS: Evidence of EBV
      infection was detected in all 11 tissue samples with dysplasia or carcinoma in
      situ. EBERs were identified in all eight samples tested, and LMP-1 was detected
      in all six of the tested samples. Six of the seven samples tested for the EBV
      termini contained clonal EBV DNA: Transcription of the latent EBV gene products,
      EBV nuclear antigen 1, LMP-1, LMP-2A, and the BamHI-A fragment, was detected in
      most of the samples. Viral proteins characteristic of lytic lesions were not
      detected. CONCLUSIONS: Preinvasive lesions of the nasopharynx are infected with
      EBV. The EBV DNA is clonal, indicating that the lesions represent a focal
      cellular growth that arose from a single EBV-infected cell and that EBV infection
      is an early, possibly initiating event in the development of nasopharyngeal
      carcinoma. Preinvasive lesions contain EBV RNAs that are characteristic of latent
      infection but not the viral proteins that are characteristic of lytic infection.
      The detection of the EBV-transforming gene, LMP-1, in all the neoplastic cells
      suggests that its expression is essential for preinvasive epithelial
      proliferations associated with nasopharyngeal carcinoma.

PMID- 7637747
TI  - Incentive spirometry to prevent acute pulmonary complications in sickle cell
      diseases.
AB  - BACKGROUND: This study was designed to determine the incidence of thoracic bone
      infarction in patients with sickle cell diseases who were hospitalized with acute
      chest or back pain above the diaphragm and to test the hypothesis that incentive
      spirometry can decrease the incidence of atelectasis and pulmonary infiltrates.
      METHODS: We conducted a prospective, randomized trial in 29 patients between 8
      and 21 years of age with sickle cell diseases who had 38 episodes of acute chest
      or back pain above the diaphragm and were hospitalized. Each episode of pain was
      considered to be an independent event. At each hospitalization, patients with
      normal or unchanged chest radiographs on admission were randomly assigned to
      treatment with spirometry or to a control nonspirometry group. Each patient in
      the spirometry group took 10 maximal inspirations using an incentive spirometer
      every two hours between 8 a.m. and 10 p.m. and while awake during the night until
      the chest pain subsided. A second radiograph was obtained three or more days
      after admission, or sooner if clinically necessary, to determine the incidence of
      pulmonary complications. Bone scanning was performed no sooner than two days
      after hospital admission to determine the incidence of thoracic bone infarction.
      RESULTS: The incidence of thoracic bone infarction was 39.5 percent (15 of 38
      hospitalizations). Pulmonary complications (atelectasis or infiltrates) developed
      during only 1 of 19 hospitalizations of patients assigned to the spirometry
      group, as compared with 8 of 19 hospitalizations of patients in the nonspirometry
      group (P = 0.019). Among patients with thoracic bone infarction, no pulmonary
      complications developed in those assigned to the spirometry group during a total
      of seven hospitalizations, whereas they developed during five of eight
      hospitalizations in the nonspirometry group (P = 0.025). CONCLUSIONS: Thoracic
      bone infarction is common in patients with sickle cell diseases who are
      hospitalized with acute chest pain. Incentive spirometry can prevent the
      pulmonary complications (atelectasis and infiltrates) associated with the acute
      chest syndrome in patients with sickle cell diseases who are hospitalized with
      chest or back pain above the diaphragm.

PMID- 7637748
TI  - Long-term course of neonatal diabetes.
AB  - BACKGROUND: Neonatal diabetes mellitus--defined here as hyperglycemia occurring
      within the first month of life that lasts for at least two weeks and requires
      insulin therapy--is a very rare form of the disease. Little is known about it,
      particularly with respect to its long-term course. METHODS: We studied two
      brothers who had neonatal diabetes and obtained follow-up information on 34
      patients described in the literature as well as information on 21 additional
      patients. Forty-seven of the patients had neonatal diabetes, as defined above,
      and in 10 others the onset was between the first and third month of life.
      RESULTS: Twenty-six of the 57 infants had permanent diabetes, 18 had transient
      diabetes, and 13 had transient diabetes that recurred when they were 7 to 20
      years old. Neonatal diabetes was associated with the Wolcott-Rallison syndrome in
      six infants, hyperuricemia due to phosphoribosyl-ATP pyrophosphatase
      hyperactivity in two, and celiac disease in two. Forty-one of 45 neonates in whom
      the duration of gestation and birth weight were known were small for their
      gestational ages. There were two pairs of affected twins and four other families
      with two or more infants with neonatal diabetes, but only three parents had
      diabetes. The incidence of neonatal diabetes mellitus in Germany has been
      estimated to be 1 in 500,000 neonates. CONCLUSIONS: Neonatal diabetes differs
      from insulin-dependent diabetes in that its course is highly variable. Some
      patients have permanent diabetes, but others have transient or lasting
      remissions.

PMID- 7637750
TI  - Long-term oxygen therapy.

PMID- 7637749
TI  - Images in clinical medicine. Double uterus with adenocarcinoma.

PMID- 7637751
TI  - Case Records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 28-1995. A 69-year-old woman with recurrent pain in the right
      lower quadrant of the abdomen and a radiographic abnormality of the cecum.

PMID- 7637752
TI  - Body weight and mortality.

PMID- 7637753
TI  - Epstein-Barr virus--increasing evidence of a link to carcinoma.

PMID- 7637754
TI  - Bone marrow transplantation versus chemotherapy in non-Hodgkin's lymphoma.

PMID- 7637755
TI  - Bone marrow transplantation versus chemotherapy in non-Hodgkin's lymphoma.

PMID- 7637756
TI  - Bone marrow transplantation versus chemotherapy in non-Hodgkin's lymphoma.

PMID- 7637757
TI  - Bone marrow transplantation versus chemotherapy in non-Hodgkin's lymphoma.

PMID- 7637758
TI  - Bone marrow transplantation versus chemotherapy in non-Hodgkin's lymphoma.

PMID- 7637759
TI  - Bone marrow transplantation versus chemotherapy in non-Hodgkin's lymphoma.

PMID- 7637760
TI  - Bone marrow transplantation versus chemotherapy in non-Hodgkin's lymphoma.

PMID- 7637761
TI  - Transplantation of fetal mesencephalic tissue in Parkinson's disease.

PMID- 7637762
TI  - Ibuprofen in patients with cystic fibrosis.

PMID- 7637763
TI  - Ibuprofen in patients with cystic fibrosis.

PMID- 7637764
TI  - Serum antibodies to the deleted dystrophin sequence after cardiac transplantation
      in a patient with Becker's muscular dystrophy.

PMID- 7637765
TI  - Cost sharing in health insurance.

PMID- 7637766
TI  - More on smoking superheroes.

PMID- 7637767
TI  - Healing by design.

PMID- 7637768
TI  - Should courts decide on euthanasia?

PMID- 7637769
TI  - Medical research charities 'can rely on peer review'.

PMID- 7637770
TI  - Fertility pioneers face 'misconduct charge'.

PMID- 7637771
TI  - Panel clears professor involved in studies of 'close encounters'.

PMID- 7637772
TI  - International collaboration.

PMID- 7637773
TI  - Polio vaccines.

PMID- 7637774
TI  - Directory to the human genome.

PMID- 7637775
TI  - Chromatin insulators. Keeping enhancers under control.

PMID- 7637776
TI  - Antigen presentation. DM exchange mechanism.

PMID- 7637777
TI  - DNA-binding proteins. Inside the MADS box.

PMID- 7637778
TI  - Conserved cell and organelle division.

PMID- 7637779
TI  - Homeotic genes and the evolution of arthropods and chordates.
AB  - Clusters of homeotic genes sculpt the morphology of animal body plans and body
      parts. Different body patterns may evolve through changes in homeotic gene
      number, regulation or function. Recent evidence suggests that homeotic gene
      clusters were duplicated early in vertebrate evolution, but the generation of
      arthropod and tetrapod diversity has largely involved regulatory changes in the
      expression of conserved arrays of homeotic genes and the evolution of
      interactions between homeotic proteins and the genes they regulate.

PMID- 7637780
TI  - Structure of serum response factor core bound to DNA.
AB  - The human serum response factor is a transcription factor belonging to the MADS
      domain protein family with members characterized from the plant and animal
      kingdoms. The X-ray crystal structure of the serum response factor core in a
      specific-recognition DNA complex shows that the functions of DNA binding,
      dimerization and accessory-factor interaction are compactly integrated into a
      novel protein unit. The intrinsic and induced conformation of the serum response
      element DNA is the principal DNA feature recognized in the specific complex.

PMID- 7637781
TI  - Two stages of visual processing for radial and circular motion.
AB  - As we move through our environment, the flow of the deforming images on our
      retinae provides rich information about ego motion and about the three
      dimensional structure of the external world. Flow-fields comprise five
      independent components, including radial and circular motion. Here we provide
      psychophysical evidence for the existence of neural mechanisms in human vision
      that integrate motion signals along these complex trajectories. Signal-to-noise
      sensitivity for discriminating the direction of radial, circular and
      translational motion increased predictably with the number of exposed sectors,
      implying the existence of specialized detectors that integrate motion signals of
      different directions from different locations. However, contrast sensitivity for
      complex motion did not increase greatly with sector number, implying that the
      specialized detectors are preceded by a first stage of local-motion mechanisms
      that impose a contrast threshold. These findings fit well with recent
      electrophysiological evidence in monkey showing that whereas motion-sensitive
      neurons in primary visual cortex respond best to local translation, many neurons
      in the medial superior temporal cortex have large receptive fields tuned to
      radial, circular or spiral motion.

PMID- 7637782
TI  - Collapsin-induced growth cone collapse mediated by an intracellular protein
      related to UNC-33.
AB  - Collapsin, a member of the newly recognized semaphorin family, contributes to
      axonal pathfinding during neural development by inhibiting growth cone extension.
      The mechanism of collapsin action is poorly understood. Here we use a Xenopus
      laevis oocyte expression system to identify molecules involved in collapsin
      signalling, because several experiments have raised the possibility that
      heterotrimeric GTP-binding proteins might participate in these events. A
      collapsin response mediator protein of relative molecular mass (M(r)) 62K (CRMP
      62) required for collapsin-induced inward currents in X. laevis oocytes is
      isolated. CRMP-62 shares homology with UNC-33, a nematode neuronal protein
      required for appropriately directed axonal extension. CRMP-62 is localized
      exclusively in the developing chick nervous system. Introduction of anti-CRMP-62
      antibodies into dorsal root ganglion neurons blocks collapsin-induced growth cone
      collapse. CRMP-62 appears to be an intracellular component of a signalling
      cascade initiated by an unidentified transmembrane collapsin-binding protein.

PMID- 7637783
TI  - Channel gating governed symmetrically by conserved leucine residues in the M2
      domain of nicotinic receptors.
AB  - In nicotinic acetylcholine receptors (nAChR), as well as glycine, GABAA (gamma
      aminobutyric acid), serotonin (5-HT3), and GluCl glutamate receptors, a leucine
      residue at the approximate midpoint of the M2 transmembrane domain (the 9'
      position) is conserved across most known subunits. Structural data for the nAChR
      suggest that the Leu 9' residues occupy a 'kink' in each of the five M2 helices
      and point into the closed channel; in the opening step, the M2 helices rotate so
      that Leu 9' side chains no longer occlude the conduction pathway. Mutation of Leu
      9' to one of several other residues slows desensitization and increases
      sensitivity to agonist. We have exploited the alpha 2 beta gamma delta
      stoichiometry of muscle nAChR to express receptors with ms* = 0 to 5 Leu 9'Ser
      mutated subunits. Strikingly, each Leu 9'Ser mutation shifts the dose-response
      relation for ACh to the left by approximately 10-fold; a nAChR with ms* = 4 is
      10(4)-fold more sensitive than the wild type. The results suggest that each of
      the five Leu 9' residues participates independently and symmetrically in a key
      step in the structural transition between the closed and open states.

PMID- 7637784
TI  - Direct and continuous assessment by cells of their position in a morphogen
      gradient.
AB  - According to the morphogen gradient concept, cells in one part of an embryo
      secrete diffusible molecules (morphogens) that spread to other nearby cells and
      activate genes at different threshold concentrations. Strong support for the
      operation of a morphogen gradient mechanism in vertebrate development has come
      from the biochemical experiments of Green and Smith, who induced different kinds
      of gene expression in amphibian blastula cells exposed to small changes in
      activin concentration. But the interpretation of these experiments has been
      complicated by recent reports that cells tested for gene expression 3 hours after
      exposure to activin fail to show the graded response previously reported at 15
      hours, a result suggesting that cells recognize their position in a gradient by
      an indirect mechanism. Here we conclude from the in situ analysis of blastula
      tissue containing activin-loaded beads that cells respond directly to changing
      morphogen concentrations in a way that resembles a ratchet-like process.

PMID- 7637785
TI  - Autocrine mitogenic activity of pheromones produced by the protozoan ciliate
      Euplotes raikovi.
AB  - Diffusible polypeptide pheromones (formerly referred to as mating-type factors,
      sex factors or gamones), which distinguish otherwise morphologically identical
      vegetative cell (mating) types from one another, are produced by some species of
      ciliates. Their most striking effect can be observed by exposing cells of one
      type to a pheromone secreted by another co-specific cell type. In the presence of
      this 'non-self' signal, these cells interrupt their vegetative life to unite
      temporarily in mating pairs. Thus ciliate pheromones have traditionally been
      associated only with mating induction. However, the identification of autocrine
      pheromone receptors suggests a broader role, which is supported by the hypothesis
      that ciliates evolved their mating-type mechanism for pursuing self-recognition.
      We now report studies, in the cosmopolitan marine sand-dwelling protozoan ciliate
      Euplotes raikovi, demonstrating that these molecules promote the vegetative
      reproduction (mitogenic proliferation or growth) of the same cells from which
      they originate. As, understandably, such autocrine pheromone activity is primary
      to that of targeting and inducing a foreign cell to mate (paracrine functions),
      this finding provides an example of how the original function of a molecule can
      be obscured during evolution by the acquisition of a new one.

PMID- 7637787
TI  - Identification of a specific Ins(1,3,4,5)P4-binding protein as a member of the
      GAP1 family.
AB  - Inositol 1,3,4,5-tetrakisphosphate (Ins(1,3,4,5)P4) is produced rapidly from
      inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) in stimulated cells. Despite
      extensive experimentation, no clearly defined cellular function has yet been
      described for this inositol phosphate. Binding sites specific for Ins(1,3,4,5)P4
      have been identified in several tissues, and we have purified one such protein to
      homogeneity. Its high affinity for Ins(1,3,4,5)P4, and its exquisite specificity
      for this isomeric configuration, suggest it may be an Ins(1,3,4,5)P4 receptor.
      Here we report the cloning and characterization of this protein as a GTPase
      activating protein, specifically a member of the GAP1 family. In vitro it shows
      GAP activity against both Rap and Ras, but only the Ras GAP activity is inhibited
      by phospholipids and is specifically stimulated by Ins(1,3,4,5)P4.

PMID- 7637786
TI  - Calcium activation of Ras mediated by neuronal exchange factor Ras-GRF.
AB  - Tyrosine kinase receptors stimulate the Ras signalling pathway by enhancing the
      activity of the SOS nucleotide-exchange factor. This occurs, at least in part, by
      the recruitment of an SOS-GRB2 complex to Ras in the plasma membrane. Here we
      describe a different signalling pathway to Ras that involves activation of the
      Ras-GRF exchange factor in response to Ca2+ influx. In particular, we show that
      the ability of Ras-GRF to activate Ras in vivo is markedly enhanced by raised
      Ca2+ concentrations. Activation is mediated by calmodulin binding to an IQ motif
      in Ras-GRF, because substitutions in conserved amino acids in this motif prevent
      both calmodulin binding to Ras-GRF and Ras-GRF activation in vivo. So far, full
      length Ras-GRF has been detected only in brain neurons. Our findings implicate
      Ras-GRF in the regulation of neuronal functions that are influenced by Ca2+
      signals.

PMID- 7637788
TI  - A human nucleoporin-like protein that specifically interacts with HIV Rev.
AB  - The Rev protein of human immunodeficiency virus type 1 (HIV-1) facilitates the
      nuclear export of unspliced and partly spliced viral RNAs. Rev contains an RNA
      binding domain, required for interaction with HIV-1 RNA, and an effector domain,
      required for RNA-bound Rev to function. The Rev effector domain is believed to
      interact with a cellular cofactor required for the Rev response and thus HIV-1
      replication. Here we report the use of a yeast two-hybrid screen to clone human
      Rev interacting protein (hRIP), which specifically interacts with the Rev
      effector domain. This hRIP protein has homology with nucleoporins, a class of
      proteins that mediate nucleocytoplasmic transport. These and other properties of
      hRIP are those expected of a Rev cellular cofactor.

PMID- 7637790
TI  - Nicotine as a drug.

PMID- 7637789
TI  - Modulation of enhancer-promoter interactions by insulators in the Drosophila
      embryo.
AB  - Insulator DNAs, or boundary elements, functionally isolate neighbouring genes by
      blocking interactions between distal enhancers and inappropriate target
      promoters. The best-characterized insulators in Drosophila correspond to a 340
      base-pair (bp) fragment from the gypsy retrotransposon, and the scs and scs'
      sequences flanking the 87A1 hsp70 locus. Here we demonstrate that both insulators
      block the interaction of defined even-skipped (eve) stripe enhancers when
      positioned between the enhancer and the target promoter. The simultaneous use of
      two stripe enhancers (eve stripes 2 and 3) provides evidence that enhancers lying
      distal to the insulator are selectively blocked. The insertion of stripe
      insulator-stripe sequences between two divergently transcribed promoters
      indicates that enhancers barred from acting on one basal promoter are fully
      accessible to appropriate regulatory factors for activating the other promoter.
      These results suggest that insulators do not propagate changes in chromatin
      structure. Finally, we present evidence that the gypsy insulator does not block
      interactions between a silencer element and a basal promoter. Taken together,
      these results suggest that insulators might not be restricted to the functional
      isolation of neighbouring genetic loci. Rather, they might function as flexible
      regulatory elements that modulate enhancer-promoter interactions within complex
      promoters and complex genetic loci.

PMID- 7637791
TI  - Gene patent study drowned as OTA sinks.

PMID- 7637792
TI  - Sacked chimpanzee centre director complains of monkey business.

PMID- 7637793
TI  - Bad manners, not good.

PMID- 7637794
TI  - Effects of DDE.

PMID- 7637795
TI  - Drugs in ancient texts.

PMID- 7637796
TI  - In praise of interdisciplinarity.

PMID- 7637797
TI  - Neuropsychology. Is dopamine a missing link?

PMID- 7637798
TI  - Virology. Evolving Darwinism.

PMID- 7637800
TI  - Palaeontology. Ecological apes and ancestors.

PMID- 7637799
TI  - Signal transduction. A target for PI(3) kinase.

PMID- 7637801
TI  - Why is dieting so difficult.

PMID- 7637802
TI  - Gene expression and mRNA.

PMID- 7637803
TI  - New four-million-year-old hominid species from Kanapoi and Allia Bay, Kenya.
AB  - Nine hominid dental, cranial and postcranial specimens from Kanapoi, Kenya, and
      12 specimens from Allia Bay, Kenya, are described here as a new species of
      Australopithecus dating from between about 3.9 million and 4.2 million years ago.
      The mosaic of primitive and derived features shows this species to be a possible
      ancestor to Australopithecus afarensis and suggests that Ardipithecus ramidus is
      a sister species to this and all later hominids. A tibia establishes that
      hominids were bipedal at least half a million years before the previous earliest
      evidence showed.

PMID- 7637804
TI  - Modulation of memory fields by dopamine D1 receptors in prefrontal cortex.
AB  - Dopamine has been implicated in the cognitive process of working memory but the
      cellular basis of its action has yet to be revealed. By combining iontophoretic
      analysis of dopamine receptors with single-cell recording during behaviour, we
      found that D1 antagonists can selectively potentiate the 'memory fields' of
      prefrontal neurons which subserve working memory. The precision shown for D1
      receptor modulation of mnemonic processing indicates a direct gating of selective
      excitatory synaptic inputs to prefrontal neurons during cognition.

PMID- 7637805
TI  - Mutations in the palmitoyl protein thioesterase gene causing infantile neuronal
      ceroid lipofuscinosis.
AB  - Neuronal ceroid lipofuscinoses (NCL) represent a group of common progressive
      encephalopathies of children which have a global incidence of 1 in 12,500. These
      severe brain diseases are divided into three autosomal recessive subtypes,
      assigned to different chromosomal loci. The infantile subtype of NCL (INCL),
      linked to chromosome 1p32, is characterized by early visual loss and rapidly
      progressing mental deterioration, resulting in a flat electroencephalogram by 3
      years of age; death occurs at 8 to 11 years, and characteristic storage bodies
      are found in brain and other tissues at autopsy. The molecular pathogenesis
      underlying the selective loss of neurons of neocortical origin has remained
      unknown. Here we report the identification, by positional candidate methods, of
      defects in the palmitoyl-protein thioesterase gene in all 42 Finnish INCL
      patients and several non-Finnish patients. The most common mutation results in
      intracellular accumulation of the polypeptide and undetectable enzyme activity in
      the brain of patients.

PMID- 7637806
TI  - Brain regions associated with retrieval of structurally coherent visual
      information.
AB  - An object's global, three-dimensional structure may be represented by a
      specialized brain system involving regions of inferior temporal cortex. This
      system's role in object representation can be understood by experiments in which
      people study drawings of novel objects with possible or impossible three
      dimensional structures, and later make either possible/impossible object
      decisions or old/new recognition decisions about briefly flashed studied and non
      studied objects. Although object decisions about possible objects are facilitated
      by prior study, there is no corresponding facilitation for impossible objects,
      thereby implicating a system that is specifically involved in the representation
      of structurally coherent visual objects. Here we show, by positron emission
      tomography (PET), that increases in blood flow in inferior temporal regions are
      associated with object decisions about possible but not impossible objects, and
      that there are increases in the vicinity of the hippocampal formation associated
      with episodic recognition of possible objects.

PMID- 7637807
TI  - Inhibition by anandamide of gap junctions and intercellular calcium signalling in
      striatal astrocytes.
AB  - Anandamide, an endogenous arachidonic acid derivative that is released from
      neurons and activates cannabinoid receptors, may act as a transcellular
      cannabimimetic messenger in the central nervous system. The biological actions of
      anandamide and the identity of its target cells are, however, still poorly
      documented. Here we show that anandamide is a potent inhibitor of gap-junction
      conductance and dye permeability in striatal astrocytes. This inhibitory effect
      is specific for anandamide as compared to co-released congeners or structural
      analogues, is sensitive to pertussis toxin and to protein-alkylating agents, and
      is neither mimicked by cannabinoid-receptor agonists nor prevented by a
      cannabinoid-receptor antagonist. Glutamate released from neurons evokes calcium
      waves in astrocytes that propagate via gap junctions, and may, in turn, activate
      neurons distant from their initiation sites in astrocytes. We find that
      anandamide blocks the propagation of astrocyte calcium waves generated by either
      mechanical stimulation or local glutamate application. Thus, by regulating gap
      junction permeability, anandamide may control intercellular communication in
      astrocytes and therefore neuron-glial interactions.

PMID- 7637808
TI  - An IL-12-based vaccination method for preventing fibrosis induced by schistosome
      infection.
AB  - The harmful fibrosis which often occurs in the context of infectious disease
      involves the excessive deposition of connective tissue matrix, particularly
      collagen, and is mostly resistant to pharmacological and immunological
      intervention. In schistosomiasis, fibrosis is associated with the granulomatous
      response to parasite eggs trapped in the liver. We have previously shown that
      interleukin (IL)-12 administered peritoneally with eggs prevents subsequent
      pulmonary granuloma formation on intravenous challenge with eggs. Here we show
      that sensitization with eggs plus IL-12 partly inhibits granuloma formation and
      dramatically reduces the tissue fibrosis induced by natural infection with
      Schistosoma mansoni worms. These results are an example of a vaccine against
      parasites which acts by preventing pathology rather than infection. IL-12 is
      known to favour the priming of TH1 rather than Th2 cells, and the effects on
      fibrosis are accompanied by replacement of the Th2-dominated pattern of cytokine
      expression characteristic of S. mansoni infection with one dominated by Th1
      cytokines. Elevated Th2 cytokine expression and fibrosis are common
      manifestations of a wide variety of infectious diseases and atopic disorders
      which might be ameliorated by vaccination with antigen and IL-12.

PMID- 7637809
TI  - An IRF-1-dependent pathway of DNA damage-induced apoptosis in mitogen-activated T
      lymphocytes.
AB  - Lymphocytes are particularly susceptible to DNA damage-induced apoptosis, a
      response which may serve as a form of 'altruistic suicide' to counter their
      intrinsic high potential for mutation and clonal expansion. The tumour suppressor
      p53 has been shown to regulate this type of apoptosis in thymocytes, but an as
      yet unknown, p53-independent pathway(s) appears to mediate the same event in
      mitogen-activated mature T lymphocytes. Here we show DNA damage-induced apoptosis
      in these T lymphocytes is dependent on the antioncogenic transcription factor
      interferon regulatory factor (IRF)-1. Thus two different anti-onco-genic
      transcription factors, p53 and IRF-1, are required for distinct apoptotic
      pathways in T lymphocytes. We also show that mitogen induction of the interleukin
      1 beta converting enzyme (ICE) gene, a mammalian homologue of the Caenorhabditis
      elegans cell death gene ced-3, is IRF-1-dependent. Ectopic overexpression of IRF
      1 results in the activation of the endogenous gene for ICE and enhances the
      sensitivity of cells to radiation-induced apoptosis.

PMID- 7637810
TI  - Protein kinase B (c-Akt) in phosphatidylinositol-3-OH kinase signal transduction.
AB  - A serine/threonine kinase, named protein kinase B (PKB) for its sequence homology
      to both protein kinase A and C, has previously been isolated. PKB, which is
      identical to the kinase Rac, was later found to be the cellular homologue of the
      transforming v-Akt. Here we show that PKB is activated by stimuli such as
      insulin, platelet-derived growth factor (PDGF), epidermal growth factor (EGF) and
      basic fibroblast growth factor (bFGF). Activation of PKB was inhibited by the
      phosphatidylinositol-3-OH kinase (PI(3)K) inhibitor wortmannin and by
      coexpression of a dominant-negative mutant of PI(3)K. PDGF receptor mutants that
      lack detectable associated PI(3)K activity also fail to induce PKB activation,
      PKB kinase activity is correlated with phosphorylation of PKB on serine. Finally,
      we show that a constructed Gag-PKB fusion protein, homologous to the v-akt
      oncogene, displays significantly increased ligand-independent kinase activity.
      Furthermore, this activity is sufficient to activate the p70 S6-kinase (p70S6K).
      These results suggest a role for PKB in PI(3)K-mediated signal transduction.

PMID- 7637811
TI  - Recognition of bZIP proteins by the human T-cell leukaemia virus transactivator
      Tax.
AB  - Human T-cell leukaemia virus type I (HTLV-I) Tax protein increases the DNA
      binding of many cellular transcription factors that contain a basic region
      leucine zipper (bZIP) DNA-binding domain. bZIP domains comprise a leucine-rich
      dimerization motif and a basic region that mediates DNA contact. How Tax
      recognizes diverse bZIPs is not understood. Here we show that no specific
      sequence of the leucine zipper is required for a Tax response. In contrast, the
      basic region is essential for the Tax-mediated DNA-binding increase, which can be
      eliminated by single substitutions of several conserved amino acids.
      Surprisingly, Tax alters the relative affinity of a bZIP for different DNA
      binding sites. Thus, through recognition of the conserved basic region. Tax
      increases DNA binding and modifies DNA site selection. Tax provides a model for
      how a single auxiliary factor can regulate multiple sequence-specific DNA-binding
      proteins.

PMID- 7637812
TI  - Mechanism of DNA-binding enhancement by the human T-cell leukaemia virus
      transactivator Tax.
AB  - Tax protein activates transcription of the human T-cell leukaemia virus type I
      (HTLV-I) genome through three imperfect cyclic AMP-responsive element (CRE)
      target sites located within the viral promoter. Previous work has shown that Tax
      interacts with the bZIP element of proteins that bind the CRE target site to
      promote peptide dimerization, suggesting an association between Tax and bZIP
      coiled coil. Here we show that the site of interaction with Tax is not the coiled
      coil, but the basic segment. This interaction increases the stability of the GCN4
      bZIP dimer by 1.7 kcal mol-1 and the DNA affinity of the dimer by 1.9 kcal mol-1.
      The differential effect of Tax on several bZip-DNA complexes that differ in
      peptide sequence or DNA conformation suggests a model for Tax action based on
      stabilization of a distinct DNA-bound protein structure. This model may explain
      how Tax interacts with transcription factors of considerable sequence diversity
      to alter patterns of gene expression.

PMID- 7637813
TI  - Model for binding of transcription factor TFIIB to the TBP-DNA complex.
AB  - Transcription factor TFIIB is essential for the formation of RNA polymerase II
      initiation complexes where it binds to the TATA-binding protein (TBP) complex
      with DNA and recruits RNA polymerase II. TFIIB is probably a target for various
      activators. Several models have been proposed for the position of TFIIB in the
      TFIIB-TBP-DNA complex. Here we examine the structure of this complex using gel
      mobility-shift assays and hydroxyl-radical footprinting. TFIIB requires at least
      seven base pairs of DNA on either side of the TATA box to form a stable TFIIB-TBP
      DNA complex. The sugar residues protected from hydroxyl-radical cleavage by the
      TFIIB-TBP complex were mapped on the crystal-structure model of the TBP-DNA
      complex. This analysis suggests that TFIIB binds beneath the concave surface of
      TBP, contacting DNA both upstream and downstream of the TATA box. Our model
      predicts that TFIIB binds close to the C-terminal stirrup of TBP and provides one
      explanation for why TBP needs to bend DNA.

PMID- 7637814
TI  - Crystal structure of Thermus aquaticus DNA polymerase.
AB  - The DNA polymerase from Thermus aquaticus (Taq polymerase), famous for its use in
      the polymerase chain reaction, is homologous to Escherichia coli DNA polymerase I
      (pol I) Like pol I, Taq polymerase has a domain at its amino terminus (residues 1
      290) that has 5' nuclease activity and a domain at its carboxy terminus that
      catalyses the polymerase reaction. Unlike pol I, the intervening domain in Taq
      polymerase has lost the editing 3'-5' exonuclease activity. Although the
      structure of the Klenow fragment of pol I has been known for ten years, that of
      the intact pol I has proved more elusive. The structure of Taq polymerase
      determined here at 2.4 A resolution shows that the structures of the polymerase
      domains of the thermostable enzyme and of the Klenow fragment are nearly
      identical, whereas the catalytically critical carboxylate residues that bind two
      metal ions are missing from the remnants of the 3'-5' exonuclease active site of
      Taq polymerase. The first view of the 5' nuclease domain, responsible for
      excising the Okazaki RNA in lagging-strand DNA replication, shows a cluster of
      conserved divalent metal-ion-binding carboxylates at the bottom of a cleft. The
      location of this 5'-nuclease active site some 70 A from the polymerase active
      site in this crystal form highlights the unanswered question of how this domain
      works in concert with the polymerase domain to produce a duplex DNA product that
      contains only a nick.

PMID- 7637815
TI  - The surface apparatus--a tool for probing molecular protein interactions.
AB  - The measurements described demonstrate the variety of protein or protein-mediated
      interactions that can be probed directly with the SFA. The distance, force and
      dynamic measurement capabilities provide tremendous potential for the
      identification and quantification of the molecular mechanisms and forces that
      both determine protein properties and influence protein function in diverse
      environments.

PMID- 7637816
TI  - Time to relax research use of patents.
AB  - The conditions under which research is exempt from European patent law are
      ambiguous, and current judicial interpretation is too restrictive. A liberal
      approach would be a welcome boost to small research-based companies.

PMID- 7637817
TI  - Electrophoretic analysis of microheterogeneity of paraproteins in a patient with
      IgD myeloma.
AB  - High-resolution two-dimensional polyacrylamide gel electrophoresis (2-DE) was
      used to analyze more precisely serum and urine specimens of a patient suffering
      from IgD myeloma associated with renal insufficiency. The application of 2-DE
      with immobilized pH gradient followed by immunoblotting revealed the presence of
      acidic monoclonal delta chains, hidden on 2-DE by albumin. This approach also
      enabled to detect two other forms of delta heavy chains expressing both reduced
      (45 kDa) and high (110 kDa) mol. weight. The analysis of urine specimen proved
      the presence of three acidic isoforms of monoclonal lambda light chains together
      with multiple monoclonal light chain fragments, which strongly suggests
      amyloidogenicity of these monoclonal light chains.

PMID- 7637819
TI  - Induction of single strand DNA breaks in workers professionally exposed to
      polycyclic aromatic hydrocarbons.
AB  - An epidemiological study was performed on 42 workers from coke works with the aim
      to evaluate the usefulness of monitoring single strand DNA breaks (SSBs) in human
      lymphocytes to assess exposure to polycyclic aromatic hydrocarbons (PAHs) as well
      as the usefulness of SSBs induction as an indicator of biological effects of
      PAHs. SSBs can be readily quantitated by a simple fluorometric assay of DNA
      unwinding. Compared with the control group, statistically significant increase in
      SSBs was observed in coke oven workers occupationally exposed to PAHs. These
      findings are in agreement with previous results obtained by a different method of
      measuring DNA damage in subjects exposed to high PAH levels. The findings
      confirmed that SSBs determination in human lymphocytes reflected the exposure to
      PAHs and the FADU method appears to be useful in the revelation of effects of
      occupational exposure to industrial air pollutants such as PAHs.

PMID- 7637818
TI  - Sensitization and photodynamic therapy (PDT) of gastrointestinal tumors with 5
      aminolaevulinic acid (ALA) induced protoporphyrin IX (PPIX). A pilot study.
AB  - 5-Aminolaevulinic acid (ALA) is a promising agent for photodynamic therapy (PDT)
      sensitization as it can be given orally and only causes skin photosensitivity for
      1-2 days. In fluorescence and photodynamic studies 26 patients with benign and
      malignant gastrointestinal tumors were given 30-60 mg ALA orally (single or
      divided doses) and biopsies were taken of tumor and normal tissue at 1-24 hours
      for fluorescence microscopy. With 30 mg/kg, highest protoporphyrin IX (PPIX)
      levels were seen in esophagus, duodenum and less in colon, but without tumor
      selectivity. Better tumor selectivity was seen in colon after 60 mg/kg (5:1). Six
      patients had transient rises in transaminases and five mild nausea. Sixteen
      patients were later treated (after further ALA) with red light (628 nm, bare or
      diffuser fibre, 50-100 J at 50 mW at each site). All but two showed subsequent
      necrosis, but only 0.5-1.5 mm of depth. PDT with ALA is simple, safe and
      promising for tumors in the gastrointestinal tract. Modification of treatment
      parameters may make it suitable for larger lesions.

PMID- 7637820
TI  - Radiosensitizer AK-2123 as modulating agent in the chemotherapy of experimental
      metastases.
AB  - Therapeutic effect of Cyclophosphamide (CPA) and radiosensitizer AK-2123 (AK)
      combination versus CPA alone in the same doses was investigated on transplanted
      LL carcinoma and B 16 melanoma. Antimetastatic efficacy of different doses of CPA
      and combined therapy was evaluated. Our data demonstrate that the effect of
      combined treatment by CPA at low uneffective doses (60 mg/kg, 40 mg/kg, 20 mg/kg
      at the 3rd and the 7th day after transplantation) and AK at low daily doses (1
      mg/kg and 0.1 mg/kg for 3-9 days after transplantation) is equal or superior to
      the effect of CPA alone at the therapeutic dose (120 mg/kg).

PMID- 7637821
TI  - Action of retinoic acid on human glioblastoma-astrocytoma--14 cells in culture.
AB  - Monolayer and agar culture techniques were used to examine the antiproliferative
      activities and morphological alterations of glioblastoma-astrocytoma (G1-As-14)
      cells induced by 20 mumol retinoic acid (RA). RA treated cells assumed flattened
      appearance and formed multilayers no longer. Most of the cells formed cross
      bridges with one another. RA treatment caused time-dependent, dose-dependent and
      cell seeding-dependent reduction of growth in both monolayer and in agar
      cultures. RA-induced growth inhibition was also affected by concentration of
      fetal bovine serum in the culture medium. All these effects could be reversed
      within 48 h after withdrawal of RA from the growth medium. The results
      demonstrated that the respective cell line was sensitive to RA-induced growth
      inhibition and morphological alterations which were generally associated with
      reduced expression of malignant phenotype.

PMID- 7637822
TI  - Evaluation of the anticancer property of a new alpha-methylene-gamma-lactone
      derivative of phthalimide.
AB  - The anticancer property of a new alpha-methylene-gamma-lactone derivative of
      phthalimide (2, NSC 640168) was evaluated in two murine ascitic tumors namely
      Ehrlich ascites carcinoma (EAC) and sarcoma-180 (S-180) by in vivo screenings and
      in a battery of human tumor cell lines by in vitro screening. It was found that
      the compound has exhibited marginal to moderate in vivo activity in EAC and S
      180, respectively, and significant in vitro cytotoxicity in SF-268, a human CNS
      tumor cell line. The compound, however, has not reached the criteria of
      significant anti-HIV activity.

PMID- 7637823
TI  - Lung toxicity of chemotherapeutic agents detected by TC-99m DTPA radioaerosol
      inhalation lung scintigraphy.
AB  - We investigated the lung toxicity of chemotherapeutic drugs in patients with
      breast cancer by means of Tc-99m DTPA aerosol scintigraphy. Thirty three patients
      who underwent surgical resection for breast cancer were divided into two groups,
      those who received a combination of adjuvant chemotherapy and those who did not.
      Group 1 consisted of 19 patients who received adjuvant chemotherapy and group 2
      consisted of 14 patients who did not received adjuvant chemotherapy.
      Chemotherapeutic agents included 5-fluorouracil 1000 mg, endoxan 1000 mg and MTX
      50 mg, all given intravenously. Aerosol lung scintigraphy was performed in all
      patients, in the supine position. The degree of lung damage was presented as the
      half clearance time (T 1/2) in minutes from the dynamic lung images. Only the
      right lung was used to analyze clearance, in order to avoid interference from
      stomach activity on the left side. The results show T 1/2 times of 68.18 +/-
      20.04 min and 94.46 +/- 34.78 min, over the right lung, for groups 1 and 2,
      respectively. The difference is significant, with a p-value of 0.016, using the
      Mann-Whitney U test. We conclude that some chemotherapeutic drugs such as MTX,
      may result in pulmonary damage and that aerosol lung scintigraphy can provide an
      objective mean for early detection of pulmonary damage during cytotoxic
      chemotherapy.

PMID- 7637824
TI  - Normobaric oxygen as a sensitizer in radiotherapy for advanced head and neck
      cancer.
AB  - The aim of this study was to evaluate radiosensitizing effect of normobaric
      oxygen breathing in radiotherapy for advanced head and neck cancers. Forty seven
      patients with advanced squamous cell carcinomas of the head and neck (7% in Stage
      III and 93% in Stage IV) were entered in the study. Breathing the pure,
      normobaric oxygen was given for 15-20 min in the treatment room. Irradiation
      started immediately after oxygen breathing. Conventional, megavoltage
      radiotherapy to the total doses in the range of 46-67.5 Gy was used. The control
      group was 46 patients with the same diagnosis and stage treated by radiotherapy
      alone. Locoregional tumor control was 36% in the study group compared to 15% in
      the control (p < 0.05). Mean survival time was 15.8 and 11.8 months, and 3-year
      survival was 19% and 2%, respectively (p < 0.05). Survival depended on total
      tumor dose and total nodal dose. No significant influence of the tumor location
      on local control and importance of the size of dose per fraction and overall
      treatment time were found. The most common failure in both groups was persistent
      tumor. Mean recurrence time was 5 months in the study group and 8 months in the
      control. Present results suggest that the use of normobaric oxygen breathing
      prior to irradiation could increase effectiveness of conventional radiotherapy
      for advanced squamous cell carcinomas of head and neck.

PMID- 7637825
TI  - Treatment of advanced esophageal cancer by means of irradiation, cisplatinum and
      5-fluorouracil.
AB  - In the years 1985-1990, 30 patients with locally advanced and/or disseminated
      cancer of the esophagus (Stages III and IV) were treated by radiotherapy (RT) and
      chemotherapy (ChT) containing cisplatinum and 5-fluorouracil (5-FU). The median
      survival of the patients was 8 months (range 2.5-39 months); 13 Stage III
      patients survived 3-36 months respectively (median 11 months), while 17 Stage IV
      patients survived 2.5-27 months, respectively (median 6.5 months). The survival
      depended statistically significantly (p < 0.05) only on the presence or absence
      of residual tumor after therapy and not on other parameters observed. Clinical
      response to treatment was evaluated in 16/30 patients as follows: CR was obtained
      in 4 patients, PR in two, and NR in 10 patients. Median survival of 4 patients
      with CR was 31 months; relatively high rate of CR (4/16) could be explained by
      the small number of patients. However, favorable survival results in individual
      patients may be expected even in larger series, though the rate responders may be
      somewhat lower than that obtained in our study.

PMID- 7637826
TI  - [Clinical variants of pseudotumor cerebri syndrome].
AB  - Increased cerebrospinal fluid pressure of usually unknown etiology is called
      pseudotumor cerebri. The key symptoms are headache, papilledema and fluctuating
      visual disturbances. Six cases are presented to illustrate the clinical
      variability of this syndrome. Headache or papilledema may be missing in
      individual cases. The clinical diagnosis can be facilitated by the recognition of
      accessory signs and symptoms, such as VIth nerve palsy, tinnitus and other
      cranial nerve disorders or neck stiffness. For the therapeutic outcome it is
      essential to detect and monitor visual disturbances early in the course of the
      disease.

PMID- 7637827
TI  - [Benzodiazepine receptor imaging with positron emission tomography and single
      photon emission tomography].
AB  - 11C-Flumazenil and 123I-iomazenil are PET and SPECT ligands that bind with high
      affinity and selectivity to central benzodiazepine receptors. These
      radiopharmaceuticals are highly suitable for the localization of epileptogenic
      foci in partial epilepsy. With 11C-flumazenil it is possible to localize
      epileptogenic foci more accurately than with 18FDG. This PET ligand is also
      superior to the SPECT ligand and therefore with its increased availability it
      will possibly become more important in the presurgical assessment of patients
      with medically intractable temporal and especially extratemporal lobe epilepsy.
      Due to the high amount of cortical GABAergic synapses, 11C-flumazenil and 123I
      iomazenil seem suitable as markers for the integrity of neuronal structure. With
      the help of these ligands, functionally disturbed areas of the brain can be
      differentiated from structural changes in patients with cerebral infarcts,
      cortical dysplasias, traumatic brain lesions or systemic degeneration. Another
      potential field of clinical use could be the individual pharmacological
      monitoring of drugs interacting with the GABAA-receptor complex. Imaging of the
      peripheral-type benzodiazepine receptor seems to be exclusively of scientific
      interest.

PMID- 7637828
TI  - [Subgroups of torticollis spasmodicus from the psychosomatic viewpoint. Results
      of a cluster analysis of 144 cases. German Study Group of Dystonia Research].
AB  - The question of subgroups in idiopathic spasmodic torticollis, which has been
      discussed in earlier studies in order to define etiologically heterogeneous
      patient populations has lost some of its relevance since with the injection of
      botulinum toxin an effective treatment is available. However, psychosocial
      distress is linked with spasmodic torticollis in a substantial number of
      patients. In order to define criteria for psychosocial interventions in addition
      to the treatment with botulinum toxin, a cluster analysis was carried out to
      identify high-risk populations in terms of psychological and social distress.
      Five subgroups were defined on the basis of eight variables. Two of these five
      groups, one group with rotational torticollis and one with laterocollis, emerged
      as particularly distressed by their physical complaints, the effects of their
      illness on various areas of life and in terms of psychological functioning. The
      consistency of the subgroups was tested and statistically confirmed by analysis
      of variance. In a cross-validation 83.02% of the ungrouped cases were predicted
      correctly. The authors suggest that the evaluation of psychological and social
      aspects of the condition should be part of the neurological assessment in order
      to offer appropriate support to patients, who reveal a high degree of
      psychological distress.

PMID- 7637829
TI  - [Myotonic dystrophy: magnetic resonance tomography and clinico-genetic
      correlations].
AB  - Myotonic dystrophy (DM) is an autosomal dominant multisystem disorder involving
      muscle, brain, heart, eyes and endocrine organs, among others. The molecular
      basis is an unstable trinucleotide repeat at the 3'-untranslated end of the
      myotonin protein kinase gene on chromosome 19 q 13.3, and the number of repeats
      correlates with the severity of muscle weakness. We performed a clinical,
      psychometric and MRI study on 43 patients with DM and correlated findings with
      the molecular analysis. Nineteen patients had mild distal muscle weakness, 17
      moderate und 7 severe weakness. Thirteen had marked cognitive deficits with
      reduced speed of cognition, low IQ, and apathy. MRI showed pathological muscle
      signal in 35 cases with a characteristic mosaic involving distal muscle groups,
      often sparing the posterior tibial muscle. Cerebral MRI showed significant
      subcortical white matter lesions in 20 cases and brain atrophy in 15 cases.
      Clinical and MRI findings of CNS and muscle both correlated with CTG repeat
      length, but did not parallel each other. DM is a significant disease of the brain
      as well as muscle, and several aspects of the disease correlate with molecular
      findings, with a threshold effect for repeats exceeding 1000 trinucleotides. The
      individual predominance of specific organ involvement probably depends on
      variable somatic mosaicism of the molecular defect.

PMID- 7637830
TI  - [Value of proximal conduction block study in diagnosis of inflammatory
      neuropathies].
AB  - Conduction block is a common finding in inflammatory neuropathies, indicating
      circumscribed demyelination. Since demyelination and conduction block are often
      localized proximally, the whole ulnar nerve including its proximal segments was
      studied fractionally in 31 patients with inflammatory neuropathies. In 5 of 15
      patients with Guillain-Barre syndrome, conduction block at the spinal roots was
      the first electrophysiological finding indicating demyelinating neuropathy.
      Segmental conduction blocks were also found in 8 of 9 patients with chronic
      inflammatory demyelinating polyneuropathies (CIDP) and 4 of 4 patients with
      atypical neuropathies. In 3 patients, multifocal motor neuropathy (MMN) could
      only be differentiated from motor neuron disease by recording proximal conduction
      block. Corresponding to clinical recovery, conduction block improved with
      immunoglobulin therapy in CIDP and MMN patients. The technique of proximal
      conduction block studies clearly improves the diagnosis of focal demyelination in
      inflammatory, treatable neuropathies. They should be performed particularly in
      patients with atypical neuropathies in whom electrophysiological tests of distal
      nerve segments show normal results.

PMID- 7637831
TI  - [Determining patient staff with regard to needs and requirement profile for
      neuropsychologists, speech therapists and occupational therapists of acute care
      neurologic clinics in Germany].
AB  - The directors of neurological emergency-care departments were asked about the
      number and work profile of psychologists, occupational and speech therapists in
      their institutions. A majority of departments in West Germany employed their own
      speech and occupational therapists. In East Germany, a majority had their own
      psychology service. Work profiles and demands for personnel did not differ
      between the East and West. On the basis of the results, recommendations are made
      for the number of therapists required in neurological emergency-care departments.

PMID- 7637832
TI  - [Neurologic rehabilitation in Bavaria. Study of the development of admission
      capacity of rehabilitation clinics 1992 to 1994].
AB  - In order to get information about capacities of neurorehabilitation for patients
      with acquired brain injuries or stroke in Bavaria, a survey concerning the time
      interval between registration and admission of the patient (waiting period) was
      carried out. Structured interviews by telephone were performed and all
      departments of neurorehabilitation and neurosurgery in Bavaria were included. The
      waiting period was calculated for the last 3 years and for each phase of
      rehabilitation using rehabilitation phase model A-D, which was proposed by the
      Deutscher Verband Rentenversicherungstrager (Association of German social pension
      Insurancies). As a result, a significant shortening of the waiting period over
      the last 3 years for almost all phases of rehabilitation has been demonstrated.
      We therefore conclude that an over capacity may develop in Bavarian
      neurorehabilitation, at least in certain regions. Quantity seems to be obtained.
      Next goal required is control of quality.

PMID- 7637833
TI  - [Increased residual urine volume after local injection of botulinum A toxin].
AB  - After major head trauma, a 28-year-old male patient developed tetraparesis with
      marked left-sided contractions of the leg adductors. Spasticity was resistant to
      antispastic drugs and intensive physiotherapy. Therefore, we injected 12.5 ng
      botulinum A toxin (Dysport) in the left adductor longus and adductor magnus.
      Eight measurements of the post-micturition residual urine of the bladder before
      botulinum-A-toxin administration gave no evidence for urinary retention. Between
      day 5 and 14 after injection we measured pathologically increased urinary volumes
      up to 130 ml at five different points of time. This case report indicates
      possible subclinical side effects on the autonomic nervous system of the urinary
      bladder.

PMID- 7637834
TI  - [Chronic recurrent meningoencephalitis simulating limbic encephalitis].
AB  - We report on a woman patient who since 1976 has suffered eight episodes of a
      meningoencephalitis with features of limbic encephalitis. The duration of the
      individual episodes has varied from 3 weeks to 2 months. Each time recovery has
      always been complete. Despite numerous cultural and serological examinations of
      blood and cerebral spinal fluid (CSF), no infectious agent has been detected. The
      etiology and entity of this illness are still unclear. To our knowledge such a
      clinical course has never been reported.

PMID- 7637835
TI  - [Comment on the contribution by M. Bahr et al.: Neuronal protection in neurologic
      diseases?].

PMID- 7637836
TI  - [Comment on the letter by M. Gress-Heister regarding the contribution by H.
      Wolfram and J. Pausch. On the value of the brief psychological performance test
      for detection of acquired impairments. Exemplified by the Lehrl and Fischer c. I.
      Test].

PMID- 7637837
TI  - [The molecular mechanism of apoptosis and its implication for neurological
      disorders].

PMID- 7637838
TI  - [The mechanism of cardiorespiratory arrest due to subarachnoid hemorrhage].
AB  - This report describes the clinical course of patients with sudden
      cardiorespiratory arrest (CRA) due to subarachnoid hemorrhage (SAH). We have seen
      fifteen patients of SAH that presented initially as CRA. All of them were
      diagnosed as SAH by CT scan. The patients were divided into two groups; one group
      (early DOA group) included 11 patients, who had been recognized as CRA within 60
      minutes from the onset of SAH, the other group (late DOA group) consisted of 4
      patients, who developed CRA more than 60 minutes after the initial onset. The
      major mechanism leading to delayed CRA in the late DOA group appeared to have
      been from brain stem herniation, but another mechanism appeared to be involved in
      sudden CRA in the early DOA group. Sixty percent of our patients with CRA due to
      SAH had a low serum potassium concentration, though hypokalemia was observed in
      only 4 out of 100 patients with CRA due to diseases other than SAH. These facts
      suggest that sympathetic hyperstimulation might result not only from stress but
      also from a disorder of the central autonomic nervous system. We speculate that
      the mechanism leading to early CRA after SAH appears to result from a disorder of
      the central autonomic nerve system.

PMID- 7637839
TI  - [Low incidence of point mutation of N-ras oncogene in human gliomas].
AB  - We examined the incidence of point mutations in codon 12 and 61 of N-ras gene in
      human gliomas using PCR with mismatched primers. This method detects point
      mutations. PCR with mismatched primers induced restriction sites in normal DNA
      but not in mutational DNA. Genomic DNAs were extracted from paraffin-embedded
      tissues and were amplified with nested PCR. Among 17 cases, point mutation has
      not been able to be found so far, when examined in codon 12 of N-ras gene and
      among 10 cases in codon 61 of N-ras gene. It can thus be said that point
      mutational activation of N-ras oncogene is an uncommon event in human gliomas.

PMID- 7637840
TI  - [Prediction of postoperative EEG changes for intractable epilepsy through a
      multidimensional autoregressive analysis].
AB  - Preoperative EEGs were quantitatively analyzed by means of a multidimensional
      autoregressive model (AR model) in order to predict postoperative EEGs. Recorded
      preoperative EEGs were digitized at an interval of 10 msec. The AR model fitting
      was executed on each digitized data. As this model described a multichannel
      feedback system having a peculiar activity in each site under observation, the
      interstructural relations could be described distinctly in the direction. Namely,
      the independent and the projected activities through the feedback circuits could
      be separately described for each brain site. Therefore, postoperative EEG could
      be simulated by elimination of the component in the AR model corresponding to
      each operative region. In this report, we presented three cases and discussed
      usefulness of this method. Case 1 was a patient with post-traumatic epilepsy, who
      was treated with focal resection. Preoperative EEGs revealed spike and wave
      discharges mainly in the right frontal region. Simulated postoperative EEGs based
      on elimination of component from the right frontal region in the AR model,
      corresponding to focal resection, revealed disappearance of spike and wave
      discharges. These findings were quite similar to observed postoperative EEGs.
      Case 2 was a patient with posttraumatic epilepsy, who was treated with anterior
      callosotomy. Preoperative EEGs revealed diffuse multifocal slow spike and wave
      discharges. Simulated postoperative EEGs, based on elimination of
      interhemispheric feedback pathways in the AR model, corresponding to anterior
      callosotomy, revealed marked lateralization of diffuse spike and wave discharges
      to the left hemisphere. These findings were qualitatively similar to observed
      postoperative EEGs. These results suggested that postoperative EEG changes could
      be well predicted by multidimensional autoregressive analysis.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7637841
TI  - [The use of TM HAKEN plate in craniofacial surgery].
AB  - Rigid internal fixation using mini/micro plate has become a frequent application
      in cranio-maxillo-facial surgery. In order to make plate fixation easier and
      reduce operative time, the TM HAKEN plate, a kind of micro plate, was devised
      which has a thorny HAKEN like an ice pick and applied to cranio-facial surgery.
      The plate is made of titanium, and th HAKEN and screw are made of titanium alloy.
      These allow contoured engagement in all three dimensions due to the flexibility
      of titanium, and firm fixation due to the physical strength of titanium alloy,
      resulting in minimized artifact on CT scan and MRI images. The fixation is
      accomplished by just driving in the plate with a hammer, and using screws. In the
      case of wide operative field, the plate is driven in directly, while in the case
      of small field, the plate is driven in with an impactor. TM HAKEN plate has been
      used for osteosynthesis in 39 cases of craniofacial surgery at the Department of
      Plastic and Reconstructive Surgery of Toho University Hospital between September
      1992 and September 1994. Of the 39 cases, 19 were cranioplasty using frozen
      preserved auto-carvarial bone, 9 were midface fractures, 6 were fixation of free
      bone grafting, and 5 were fixation of artificial bone (hydroxyapatite-tricalcium
      phosphate composite ceramics) grafting. Satisfactory results were obtained in all
      cases without any difficult complications such as infection, exposure or
      migration. In addition, reliable post-operative evaluations and follow-ups were
      possible with reduced artifact on CT scan and MRI images.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7637842
TI  - [A case of painful tic convulsif due to cerebellopontine angle epidermoid tumor
      which could not be clearly detected by MRI].
AB  - A case of painful tic convulsif (trigeminal neuralgia and ipsilateral hemifacial
      spasm) caused by cerebellopontine angle epidermoid tumor is presented. This tumor
      was compressed to the trigeminal nerve, and became attached to the facial and
      auditory nerves. The facial nerve exit-zone of brain stem was also compressed by
      the tumor along with a branch of the posterior inferior cerebellar artery. Total
      removal of the tumor was carried out and neuralgia and facial spasm disappeared.
      Painful tic convulsif caused by brain tumor is rare (eight cases in the
      literature plus our case), but epidermoid tumor is not rare as a cause of this
      complaint (seven in eight cases). In preoperative examination of this case, we
      could not detect this epidermoid in the cerebellopontine angle, because this
      tumor was the same intensity as CSF liquid on magnetic resonance imaging (T1 and
      T2 weighted image) and exerting hardly any mass effect on the brainstem. On
      encountering a case of painful tic convulsif of unknown origin despite the usual
      preoperative examinations, it may be useful that same kind of brain tumor,
      especially, epidermoid might be concealed in the cerebellopontine angle lesion.

PMID- 7637843
TI  - [A case of dural arteriovenous malformation in the anterior fossa associated with
      an occlusion of the unilateral middle cerebral artery with moyamoya phenomenon].
AB  - The authors report a case of dural arteriovenous malformation (dAVM) in the
      anterior fossa that was associated with an occlusion of the unilateral middle
      cerebral artery with Moyamoya phenomenon. The patient was a 79-year-old man
      referred to our department with an episode of consciousness disturbance and
      headache. Computed tomography scan showed intracerebral hematoma in the left
      frontal lobe, combined with left frontal subdural hematoma and subarachnoid
      hemorrhage. Angiography revealed dAVM in the left anterior fossa, fed by the
      bilateral ethmoidal and the bilateral middle meningeal arteries, and draining
      into the superior and inferior sinuses through the pial veins with vascular sacs.
      While angiography revealed an occlusion of the right middle cerebral artery (M1
      portion) good collaterals via leptomeningeal anastomosis had developed. T1
      weighted magnetic resonance (MR) images showed an intracerebral hematoma as a low
      intensity area, and flow-void areas were indicative of vascular sacs. Time-of
      flight MR angiography also clearly showed dAVM in the left anterior fossa. Co
      existence of an occlusion of an intracranial major artery and dAVM in this
      location has not been reported previously and it was speculated that this
      association had occurred by chance.

PMID- 7637844
TI  - [A case of hemorrhagic mixed cerebrovascular malformation of the brainstem
      draining through a transpontine vein].
AB  - A case of mixed cerebrovascular malformation of the brainstem with pontine
      hemorrhage is reported. The mixed cerebrovascular malformation was composed of
      medullary venous malformation, one hemorrhagic and another non-hemorrhagic mass.
      The latter masses were thought to be cavernous venous malformations by their MR
      findings. The medullary venous malformation drained to the anterior
      pontomesencephalic vein through a transpontine vein. A 70-year-old man,
      complaining of aggravation of left hemiparesis, was admitted to our department.
      His past history included traumatic cervical myelopathy and diabetic neuropathy.
      CT revealed a pontine hemorrhage with linear enhancement. Depending on MRI
      findings, the hemorrhage was thought to be an intratumoral hemorrhage within the
      cavernous venous malformation. Cerebral angiogram demonstrated medullary venous
      malformation. The malformation drained to the anterior pontomesencephalic vein
      through a transpontine vein. The linear enhancement was the transpontine vein
      itself. Medullary venous malformations in the brainstem are rare. With MRI, the
      transpontine vein is thought to be a characteristic feature of medullary venous
      malformation of the brainstem. We suggest that most cases of hemorrhagic
      medullary venous malformations are mixed cerebrovascular malformations. We
      emphasize the need for precise examination of other types of vascular lesions
      coexisting with medullary venous malformations.

PMID- 7637845
TI  - [Intracranial plasma cell granuloma: a case report].
AB  - Plasma cell granuloma occurs most frequently in the lung and upper respiratory
      tract; fewer than ten cases have been reported to occur in the central nervous
      system. A case of intracranial plasma cell granuloma in a 69-year-old male was
      reported. He visited our clinic, complaining of progressive visual disturbance.
      The CT in this patient showed a suprasellar mass, diagnosed as a tuberculum
      sellae meningioma. Over a 10-year observation period the tumor grew remarkably
      and, when finally removed, it proved to be a plasma cell granuloma. This report
      presents CT scans and MR images and a review of the literature relevant to this
      rare intracranial lesion. The most common preoperative diagnosis in these cases,
      as reported here, was meningioma. Although plasma cell granuloma rarely occurs
      intracranially, the existence of this entity should be borne in mind in the
      differential diagnosis of meningioma.

PMID- 7637846
TI  - [Leiomyosarcoma metastatizing to the sphenoid bone presenting exophthalmos: a
      case report].
AB  - A rare subcutaneous leiomyosarcoma metastatizing to the sphenoid bone and
      presenting exophthalmos is reported. A 56-year-old female presented with
      protrusion of the right eye and a slowly growing lump on the right temporal
      region. Six years previously, she had undergone removal of a subcutaneous mass in
      the back, which was histologically diagnosed in another hospital as
      leiomyosarcoma. She had undergone four other operations, including removal of
      local recurrences and a right renal metastasis. On admission, physical
      examination showed no neurological deficits. Craniogram revealed an osteolytic
      lesion without marginal sclerosis in the right sphenoid bone. CT showed an
      inhomogeneously enhanced mass with irregular expansion of the diploic space,
      which was partly invading the right orbit. MRI demonstrated an extradural mass in
      the right sphenoid region, which was slightly low-intense in T1-weighted image,
      high-intense in T2-weighted image, and inhomogeneously enhanced by Gd-DTPA. Right
      external carotid angiogram showed a highly vascular stain fed by meningeal
      arteries. Radionuclide bone scintigram showed multiple high-uptake areas in the
      left femoral head, the ribs, and the sphenoid bone. Preoperative embolization of
      the tumor vessels fed by the external carotid artery was performed. Following
      this procedure, the tumor stain disappeared completely. The tumor was totally
      excised with minimal bleeding through an orbitozygomatic approach. The tumor was
      loosely adherent to the dura and periorbit. The bone defect was covered with a
      methylmethacrylate resin plate. the histological examination demonstrated
      fascicular arrangement of the spindle shaped cells with mitotic figures.
      Immunohistochemical studies showed that most tumor cells were positive for actin
      and myosin, but negative for desmin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7637847
TI  - [Two cases with metastatic intracerebral alveolar soft part sarcoma].
AB  - The alveolar soft part sarcoma (ASPS) is a rare soft tissue tumor which usually
      occurs in the lower extremity of young girls. The incidence of metastasis is said
      to be highest in the lung (38%), and second highest in the bone and brain (33%).
      This report describes two cases of metastatic intracerebral alveolar soft part
      sarcoma, originating in the lower extremity. A female patient noticed a painless
      swelling in her right leg at the age of 11, and 10 years later she underwent
      total removal of the tumor. The diagnosis was alveolar soft part sarcoma. At 37
      she was admitted to our service with a diagnosis of cerebral metastasis in the
      left frontal lobe. Since then she has undergone surgical removal 4 times for
      recurrent cerebral metastasis and twice for lung metastasis. Now she is 55 years
      old and doing well except for mild left hemiparesis. She survives without
      cerebral or general metastasis 44 years following the onset of the sarcoma in her
      right leg and 18 years following the onset of the metastatic brain tumor. A 30
      year-old man, who noticed a painless swelling in his left thigh in January 1991,
      underwent total removal of the tumor and the diagnosis was alveolar soft part
      sarcoma. He was admitted to our service with no neurological deficits in October
      1992, but a CT scan showed a metastatic brain tumor in the left parieto-occipital
      region. Total removal of this metastatic brain tumor was successfully performed
      in November 1992. However, he died because of multiple brain and lung metastasis
      in February, 1994.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7637848
TI  - [A case of intracranial malignant meningioma with extraneural metastases].
AB  - A case of intracranial malignant meningioma with remote metastases to the bones
      is reported. A 66-year-old man with regrowth of right sphenoid ridge meningioma,
      whose meningioma had partially been removed 15 years before, was admitted to our
      clinic. The tumor was large enough to protrude into the lateral and third
      ventricles, and involved the right internal carotid, middle cerebral, anterior
      cerebral artery and optic nerve. The tumor had irregular contour, and was
      heterogeneously enhanced by Gd-DTPA on MRI. An operation was performed, but a
      part of the tumor around these main arteries could not be removed.
      Histopathological examination revealed anaplastic meningioma, resulting from
      malignant change. Radiotherapy was performed postoperatively and the patient was
      discharged. Seven months after the operation he complained of posterior nuchal,
      back, and lumbar pain. Radiological examination revealed multiple punched-out
      lesions in the ribs and vertebrae, which were histologically demonstrated to be
      metastases of intracranial anaplastic meningioma. Radiotherapy was carried out
      for the cervical vertebrae, but his symptoms persisted. He died of pneumonia 10
      months after the operation.

PMID- 7637849
TI  - [An acute epidural hematoma soon after nose blowing: a case report].
AB  - We reported a very rare case of an epidural hematoma soon after nose blowing. A
      22-year-old male visited our hospital complaining of severe headache and nausea
      soon after he blew his nose. Thirteen years ago, he had a ventriculo-peritoneal
      (V-P) shunt operation for a pineal region tumor which had not recurred after
      irradiation. His left auditory tube had been patent. He hit his head about 3
      months ago. On his arrival, his consciousness was almost clear but we observed
      slight right hemiparesis. Computed tomography of his head obtained on the first
      day showed the air in the hematoma in the left parietal epidural space which
      penetrated his petrosal bone from the mastoid air cells. Removal of his epidural
      hematoma was performed the next day and there was no abnormality of his parietal
      bone, dura and meningeal arteries. We supposed that nose blowing was what
      triggered his epidural hematoma. From pressure of nose blowing, the air of his
      nasopharyngeal space passed through his patent auditory tube into the tympanic
      cavity, and entered into the epidural space penetrating a microfracture or
      dissociation in the petrosal bone. In addition to this, V-P shunt system and the
      looser adhesion of dura to the skull in the young promoted entrance of air.
      Associated with formation of epidural hematoma in this case were four factors,
      "patency of auditory tube", "defect or microfracture of petrosal bone", "V-P
      shunt", "younger age" and triggered by nose blowing.

PMID- 7637850
TI  - [Subdural abscess following chronic subdural hematoma].
AB  - This is a report of subdural abscess following chronic subdural hematoma. An 86
      year-old male was admitted to our hospital due to drowsiness and left
      hemiparesis. He had been suffering from a spike fever which originated during
      chronic cholecystitis and cholelithiasis and which had continued since 2 years
      prior to admission. On admission, CT scans revealed right chronic subdural
      hematoma, and the collection of a few old hematomas was suspected in the left
      subdural space. An emergency removal of the right hematoma was carried out by
      using right single burr hole. It was found that the old hematoma accompanied a
      yellow-white abscess in the subdural space. Escherichia coli were detected from a
      bacterial culture of the abscess. Postoperative enhanced MRI clearly showed the
      capsule of the right subdural abscess, and the left chronic subdural hematoma.
      Removal of the left hematoma was performed by using a left single burr hole. But
      the abscess did not exist in the left subdural space, and only old hematomas had
      collected there. The bacterial culture of the left old hematoma was negative.
      Escherichia coli might be implanted on the capsule of the right chronic subdural
      hematoma by bacteremia derived from chronic cholecystitis. It was considered that
      the formation of the subdural abscess might have developed through the
      deterioration of the immunological function under the influence of senility.

PMID- 7637851
TI  - Levels of emotional awareness and the degree of right hemispheric dominance in
      the perception of facial emotion.
AB  - To examine correlates of individual differences in the degree of right
      hemispheric dominance in the perception of facial emotion, 51 medical students
      completed the Levy Chimeric Faces Test and an independent measure of
      differentiation and complexity in the processing of emotional information, the
      Levels of Emotional Awareness Scales. A strong positive correlation was observed
      between the two measures, especially when variance due to verbal ability was
      removed and native English speakers only were included. These results suggest
      that as right hemisphere dominance in the perception of facial emotion increases,
      the ability to perceive complexity during the processing of emotional information
      increases.

PMID- 7637852
TI  - Laterality in facial expressions and its effect on attributions of emotion and
      personality: a reconsideration.
AB  - Are there consistent differences between the emotions attributed to the right and
      left hemiface? Six studies investigated this old question, using a new technique
      of computerized image reconstruction that eliminates several confounding factors
      common in previous studies. Findings suggest that there are no consistent
      differences between the emotions and personality attributed to the right and the
      left hemiface. Nevertheless, when the two hemifaces were simultaneously compared
      on intensity, the left hemiface showed greater intensity in posed smiles. As a
      whole, the present study suggests the possibility of a slight inference of brain
      laterality in posed expressions, but not in resting faces.

PMID- 7637853
TI  - The effect of task complexity on reaction times in memory scanning and visual
      discrimination in Parkinson's disease.
AB  - Within the context of the bradyphrenia debate, two experiments designed to
      measure the cognitive speed of Parkinson patients (PD) were conducted with 58
      subjects. The experiments took the form of a high-speed memory scanning task
      using memory sets consisting of one-six words or one-six abstract figures. In a
      visual discrimination task, two simultaneously presented abstract images had to
      be compared, the complexity of the images being varied through four stages. Motor
      response was constant, reaction time was the dependent variable. PD differed from
      matched controls in the level (significant only in scanning) but in neither
      experiment in the slope of reaction time curves. Interaction group x complexity
      (MANOVA) was not significant. Correlations between disease parameters and a
      'complexity effect' measure were low throughout. However, the link to general
      intelligence was significant. The findings contradict the conventional
      bradyphrenia hypothesis.

PMID- 7637854
TI  - Serial reaction time learning and Parkinson's disease: evidence for a procedural
      learning deficit.
AB  - This paper presents evidence in support of a serial reaction time (SRT) deficit
      associated with Parkinson's disease, and related to the acquisition or execution
      of serial-order information. Eleven patients with idiopathic Parkinson's disease,
      and 10 age-matched but otherwise healthy control subjects, were compared on a
      variant of the SRT task introduced by Nissen and Bullemer (Cognit. Psychol. 19, 1
      32, 1987). The results of this study clearly demonstrate that PD patients produce
      a quite different pattern of RT performance to that of control subjects. Such a
      pattern of results may reflect either: (1) a deficit in the patients' ability to
      learn the temporal order information provided by a repeating sequence of target
      locations in the SRT task; or (2) a deficit in the patients' ability to express
      temporal order information provided by the repeating sequence of target locations
      in the SRT task.

PMID- 7637855
TI  - The efficacy of kinesthetic reading treatment for pure alexia.
AB  - This paper presents an effective treatment for pure alexia by a type of single
      case design, which we termed a "material-control single-case design" [Sugishita
      et al., Neuropsychologia, Vol. 31, 559-569, 1993]. Two patients with pure alexia
      were treated using kinesthetic reading (reading by tracing or copying the outline
      of each letter with the patient's finger). The results clearly demonstrated that
      both patients significantly improved their reading and copying performances.
      Their recovery of reading performance arose from improvement in copying. The
      results of tachistoscopic reading tests suggested that the patient obtained the
      ability to read without kinesthetic movements.

PMID- 7637856
TI  - Recall of self-generated arm movements by patients with unilateral cortical
      excisions.
AB  - In previous work, Leonard and Milner (Neuropsychologia, 29, 47-58, 1991)
      demonstrated that patients with large excisions from the right frontal lobe have
      difficulty in reproducing accurately the extent of examiner-defined arm
      movements, the displacements being made without the aid of vision. The impairment
      in the right frontal-lobe group was not dependent on recall-condition, being
      apparent irrespective of the presence of a delay, suggesting that the deficit was
      primarily one of encoding. We then went on to show that these same patients have
      a short-term memory deficit when recalling terminal position of examiner-defined
      arm movements (Neuropsychologia 29, 629-640, 1991). From these investigations we
      concluded that the right frontal lobe is critically involved in the monitoring of
      information related to movement. In the present study 58 patients with unilateral
      temporal- or frontal-lobe excisions were tested on two kinesthetic tasks that
      required the subjects themselves to select terminal positions, or movement
      extents, thereby reducing dependence on peripheral feedback. Patients with right
      frontal-lobe lesions could reproduce these self-generated movements normally,
      indicating that when demands on feedback are reduced the frontal-lobe
      contribution is not critical.

PMID- 7637857
TI  - Are the frontal lobes implicated in "planning" functions? Interpreting data from
      the Tower of Hanoi.
AB  - Twenty adult patients with lesions in the prefrontal cortex were tested on the
      Tower of Hanoi puzzle. The performance of patients was significantly worse than
      that of controls. This difference could not be accounted for in terms of a
      general decline in intelligence or memory, or by the size of the lesion. The
      results further suggest that both patients and controls used the same general
      strategy to solve the problem and that patients' difficulties with the task have
      little to do with planning or "look ahead" deficits (as is generally assumed in
      the neuropsychology literature). Patient performance is best explained in terms
      of an inability to see or resolve a goal-subgoal conflict. This interpretation is
      compatible with several existing accounts of frontal lobe dysfunction that
      postulate a failure of inhibition of a prepotent response to explain poor
      performance on the Wisconsin Card Sorting task, the Stroop task, the Antisaccade
      task, the A-Not-B task, and the Delayed Alternation task.

PMID- 7637858
TI  - Spatial characteristics of thematic role representation.
AB  - Humans use language to describe actions by mapping the thematic roles of agent
      (doer of actions) and patient (recipient of actions) on the grammatical
      categories of subject and object. The extent to which thematic roles can be
      conceptualized independent of language is not known. If nonlinguistic
      conceptualization of thematic roles is possible, then representation of these
      roles would evidence nonlinguistic characteristics. Motivated by observations in
      an aphasic man, we wished to learn if thematic roles are conceptualized
      spatially. Normally subjects were asked to draw stick figures depicting the
      thematic roles of agent and patient. They demonstrated a systematic spatial bias
      in locating agents to the left of where they located patients. This bias,
      somewhat mitigated by ordering effects of motor output and auditory input, was
      brought into clearest focus when subjects depicted thematic roles in a context
      stripped of surface sentential form. These data imply that, in their nascent
      form, the thematic roles of agent and patient are spatially represented prior to
      being projected on grammar.

PMID- 7637859
TI  - She is not a beauty even when she smiles: possible evolutionary basis for a
      relationship between facial attractiveness and hemispheric specialization.
AB  - The asymmetrical status of facial beauty has rarely been investigated. We studied
      positive facial characteristics, attractiveness and smiling, through the use of
      left-left and right-right composites of unfamiliar faces of women and men with
      natural expressions. Results showed that women's right-right composites were
      judged significantly more attractive than left-left composites while there was no
      left-right difference in men's composites (Experiment 1). On the other hand, left
      left composites were judged to have more pronounced smiling expressions than
      right-right composites in both women's and men's faces (Experiment 2). The
      results confirm previous findings for leftward facial expressiveness and show for
      the first time asymmetry in facial attractiveness and a difference in its
      manifestation in women's and men's faces. The findings have biological
      implications for the relationship between the appearance of the sides of the face
      and hemispheric specialization. The organization of beauty in the human face may
      have been shaped by evolutionary pressures on facial asymmetries, especially as
      they pertain to mate selection.

PMID- 7637860
TI  - Identification of sensory nerve cells in a peripheral organ (the intestine) of a
      mammal.
AB  - It is commonly believed that the cell bodies of mammalian sensory neurons are
      contained within spinal and cranial sensory ganglia associated with the central
      nervous system or within the central nervous system itself. However, strong
      circumstantial evidence implies that some sensory neurons are contained entirely
      within the gastrointestinal tract. We have investigated this possibility by using
      intracellular methods to record the responses of myenteric neurons in the guinea
      pig small intestine to physiological stimuli applied to the neighbouring mucosa.
      The results show that the myenteric plexus contains a population of
      chemosensitive sensory neurons and that these neurons correspond to neurons with
      AH electrophysiological properties and Dogiel type II morphology. This is the
      first direct evidence that some sensory neurons are contained entirely within the
      peripheral nervous system.

PMID- 7637861
TI  - Cholinergic lesions by 192 IgG-saporin and short-term recognition memory: role of
      the septohippocampal projection.
AB  - Two experiments examined the effects of cholinergic basal forebrain lesions by
      intraventricular and intrahippocampal infusions of the immunotoxin 192 IgG
      saporin on recognition memory in an operant delayed-non-matching-to-position task
      in rats. Intraventricular infusions produced extensive reductions in cortical and
      hippocampal choline acetyltransferase activity in the first experiment.
      Behaviourally, a mixed delay-dependent/independent accuracy deficit and increased
      biased responding was observed post-lesioning. Thus, both mnemonic as well as non
      mnemonic processes were affected by the lesion. This performance deficit was
      indistinguishable from the impairment induced by acute intraventricular
      injections of the choline uptake inhibitor hemicholinium-3, which suggests that
      cholinergic damage induced by 192 IgG-saporin disrupted performance. In the
      second experiment more discrete intrahippocampal 192 IgG-saporin lesions were
      made, which reduced hippocampal choline acetyltransferase activity about 57%,
      although this reduction was not as extensive as following intraventricular
      injections. Although intrahippocampal lesions also impaired non-matching
      accuracy, this effect failed to reach significance during most stages of the
      experiment. Scopolamine just failed to significantly impair (P = 0.053)
      performance in hippocampal lesioned rats more than in controls. The nicotinic
      antagonist mecamylamine did not affect the lesion-induced changes in performance.
      These results suggest that the cholinergic basal forebrain, including the
      septohippocampal system, is important for the mediation of recognition memory,
      and muscarinic receptor-mediated mechanisms may be of greater importance than
      alterations of nicotinic receptor-mediated processes in the septohippocampal
      system.

PMID- 7637862
TI  - C-Fos expression in the rat brain after pharmacological stimulation of the rat
      "mediodorsal" thalamus by means of microdialysis.
AB  - In order to visualize target cells of thalamic projections in the rat brain we
      examined the induction of c-fos messenger RNA and Fos-like immunoreactivity
      following stimulation of the "mediodorsal" thalamus (midline, mediodorsal and
      intralaminar nuclei) in freely moving rats. The thalamic neurons were activated
      through disinhibition by perfusion of the GABAA antagonist bicuculline-methyl
      chloride via a microdialysis cannula placed in the mediodorsal nucleus of the
      thalamus. The rats were allowed a recovery period of at least 20 h after surgery
      before being coupled to the perfusion pump. Cannula implantation with or without
      4 h of Ringer perfusion caused hardly any detectable c-fos expression in the
      brain, but 20 min of bicuculline (0.1 mM) perfusion induced high levels of c-fos
      messenger RNA and Fos protein expression in the area adjacent to the dialysis
      membrane, indicating activated thalamic neurons. In situ hybridization as well as
      immunohistochemical analysis of the frontal cortical areas and limbic structures
      showed a rapid, specific and transient c-fos expression in the medial and lateral
      prefrontal cortex, nucleus accumbens, mediodorsal striatum, claustrum, nucleus
      reticularis of the thalamus and amygdala. The overall spatial distribution of the
      c-fos response was comparable to the innervation patterns of thalamic efferents
      known from anatomical tracing experiments. The rats were perfused with Ringer
      while asleep, but they woke up during treatment with bicuculline and displayed an
      increase in general behavioural activity, which could be correlated to the amount
      of bicuculline measurable in the dialysate. Pathological behaviours, such as
      epilepsy, were not noticeable during bicuculline treatment. These results show
      that it is possible to selectively activate defined anatomical pathways by
      pharmacological application of drugs using microdialysis in unanesthetized
      unrestrained animals and to visualize the transsynaptically activated target
      neurons of these projections. We conclude that this novel experimental approach
      is indeed suitable for studying functional anatomical pathways.

PMID- 7637863
TI  - Gamma-hydroxybutyrate promotes oscillatory activity of rat and cat
      thalamocortical neurons by a tonic GABAB, receptor-mediated hyperpolarization.
AB  - The actions of gamma-hydroxybutyrate, a drug known to lead to an increase in
      nocturnal slow wave sleep and induce epileptic states following systemic
      application, on the membrane properties of thalamocortical neurons from brain
      slices of the rat and cat dorsal lateral geniculate nucleus were studied using
      sharp electrode intracellular recordings. Gamma-hydroxybutyrate applied by
      addition to the perfusion medium led to a concentration-dependent and reversible
      hyperpolarization of the membrane potential accompanied by a decrease in apparent
      input resistance (0.1 mM: 2.3 +/- 0.3 mV, 9.5 +/- 1.0%; 10 mM: 11.3 +/- 1.3 mV,
      37.5 +/- 10.8%, respectively). In six of seven neurons the iontophoretic or bath
      (0.1-0.2 mM) application of low concentrations of gamma-hydroxybutyrate led to a
      hyperpolarization accompanied by the appearance of low-frequency (< 4 Hz)
      membrane potential oscillations crowned by bursts of action potentials, when the
      membrane potential of these neurons was initially set depolarized to the range
      where ongoing oscillatory activity occurred. The gamma-hydroxybutyrate-elicited
      hyperpolarization was reversibly antagonized by the co-application of the GABAB
      receptor antagonist CGP 35348 (0.4-1 mM), but was not affected by the putative
      gamma-hydroxybutyrate receptor antagonist NCS 382 (0.1-5 mM) or tetrodotoxin (1
      microM), suggesting that gamma-hydroxybutyrate tonically activates postsynaptic
      GABAB receptors. The gamma-hydroxybutyrate-induced promotion of oscillatory
      activity and action potential burst firing of thalamocortical neurons may be one
      mechanism by which gamma-hydroxybutyrate leads to an increase in the deep stages
      of sleep and the generation of electroencephalogram and behavioural patterns
      typical of absence epilepsy.

PMID- 7637864
TI  - A persistent sodium current in acutely isolated histaminergic neurons from rat
      hypothalamus.
AB  - Histamine neurons acutely dissociated from the tuberomammillary nucleus of the
      rat hypothalamus were studied in whole-cell and cell-attached patch-clamp
      experiments. Electrophysiological properties of dissociated cells were found to
      be similar to those recorded in slice experiments using microelectrodes.
      Tuberomammillary neurons fired spontaneously and this activity persisted when Cs+
      (1.5 mM) was added to, or when K+ was removed from the extracellular solution. In
      whole-cell experiments a persistent tetrodotoxin-sensitive inward current was
      recorded. In cell attached recordings voltage-gated sodium channels displayed
      either normal or non-inactivating behavior. These results provide a further
      analysis of the properties of histaminergic neurons and indicate that spontaneous
      activity is intrinsic to individual neurons. Evidence for a non-inactivating
      tetrodotoxin-sensitive sodium current is presented. Single channel recordings
      indicate that this current is the result of non-inactivating behavior of sodium
      channels. Such a current is well suited for biasing tuberomammillary neurons
      toward spontaneous activity.

PMID- 7637865
TI  - Reception of low-intensity millimeter-wave electromagnetic radiation by the
      electroreceptors in skates.
AB  - Low intensity millimeter-wave electromagnetic radiation of less than 10 mW cm-2
      power intensity has a nonthermal effect on the body and it is widely used in
      medical practice for treatment of various diseases. Nevertheless, the effect of
      EMR on biological tissues is not understood. The skin and its sensory receptors
      are considered to be responsible for EMR reception, but this has yet to be
      confirmed. The present experiments were designed to study the effect of
      millimeter-wave electromagnetic radiation on the ampullae of Lorenzini in skates,
      which are very sensitive to weak electrical stimuli at low frequency. Reception
      of low-intensity millimeter-wave electromagnetic radiation at 37-55 GHz by the
      electroreceptors (ampullae of Lorenzini) in the skate has been shown. At a power
      intensity of 1-5 mW cm-2 irradiating the duct opening at 1-20 mm distance caused
      a transient increase in the firing rate of a single afferent unit. When the power
      intensity was increased inhibitory responses were also observed. Some receptors
      responded with a prolonged excitatory activity lasting up to 30 min to the
      irradiation of the duct opening. Direct irradiation of the sensory cells produced
      only an inhibition, probably due to a rise in temperature. It is proposed that
      millimeter-wave electromagnetic radiation generates a d.c. potential at the
      vicinity of duct opening which can be detected by the electroreceptors.

PMID- 7637866
TI  - The immunological impairment of arcuate neuropeptide Y neurons by ricin A chain
      produces persistent decrease of food intake and body weight.
AB  - Neuropeptide Y is demonstrated as a potent orexigenic peptide when injected into
      the rat hypothalamic paraventricular nuclei. The neuropeptide Y innervation of
      paraventricular nuclei originates from both hypothalamic arcuate nuclei and
      brainstem neurons, whose specific role in the control of food intake is still
      under discussion. To assess the role of the arcuate neuropeptide Y in the
      regulation of food intake, we propose a new method for immunologically impairing
      the neuronal secretion of neuropeptide Y from a unique brain site. The monoclonal
      antibody to the neuropeptide Y precursor epitope, the C-flanking peptide, was
      microinjected with two cellular toxins (the ricin A chain and the monensin) into
      the hypothalamic arcuate nuclei or paraventricular nuclei. One microinjection
      into the arcuate nuclei reduced the food intake and body weight gain for 10 days.
      It prevented the food intake stimulation usually induced by a 12 h food
      deprivation. This decrease of food intake was not due to the aversive properties
      of monoclonal antibody or cellular toxins, or the immunoneutralization of the
      biologically active neuropeptide Y, because (i) the acute effect of the
      microinjection into the arcuate nuclei promoted a transient increase of the food
      intake likely induced by a strong release of neuropeptide Y from the arcuate
      neurons which were immunologically damaged, and (ii) the C-flanking peptide
      monoclonal antibody binds neither neuropeptide Y nor its receptors. The
      microinjection was inefficient when C-flanking peptide monoclonal antibody was
      replaced by non-specific rat immunoglobulins or when the C-flanking peptide
      monoclonal antibody/toxins mixture was injected into the paraventricular nuclei.
      The data bring further arguments in two domains.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7637867
TI  - The messenger RNAs encoding metabotropic glutamate receptor subtypes are
      expressed in different neuronal subpopulations of the rat suprachiasmatic
      nucleus.
AB  - Glutamate is the principal transmitter of retinal projections to the rodent
      suprachiasmatic nucleus, a circadian clock synchronized with the light-dark cycle
      through the activation of glutamate receptors of the ionotropic type. In vitro,
      an intracellular mobilization of calcium can be induced by glutamate within cells
      of the suprachiasmatic nucleus maintained in a calcium-free medium, suggesting a
      participation of metabotropic glutamate receptors coupled to phospholipase C.
      Using in situ hybridization histochemistry, we examined the expression of
      messenger RNAs encoding the mGluR1 and mGluR5 subtypes of metabotropic glutamate
      receptors in the suprachiasmatic nucleus of the adult rat and during postnatal
      development. In the adult, mGluR1 was expressed in a small subset of neurons
      segregated caudally within the ventrolateral subdivision of the nucleus, while
      mGluR5 was mainly expressed in ventrolateral neurons within the middle third of
      the nucleus. Both subtypes were expressed in morphologically similar small cells,
      but mGluR5 was also solely expressed in a small population of larger neurons
      located at the dorsalmost aspect of the ventrolateral subdivision. In addition,
      with mGluR1 probe silver grain clusters exhibiting a grain density close but
      below the significant level were observed throughout the ventrolateral
      subdivision of the nucleus. At birth, mGluR1 and mGluR5 were similarly expressed
      throughout the caudal half of the nucleus. The expression of mGluR1 increased
      during early postnatal development and exhibited an adult pattern at postnatal
      day 21. The expression of mGluR5 increased from postnatal day 7 and reached the
      adult pattern at postnatal day 45. These observations suggest that each subtype
      of metabotropic glutamate receptor coupled to phospholipase C underlies specific
      roles within the rat suprachiasmatic nucleus during postnatal development and in
      the adult. In the adult, ionotropic and metabotropic receptors likely co
      expressed within neuronal subsets located in the retinal terminal field may have
      interactive and/or additive effects on intracellular calcium concentration.
      Metabotropic receptors may thus participate in the mediation of photic
      information conveyed to a subset of neurons. During postnatal development,
      metabotropic receptors may play a role in the maturation of glutamatergic
      synapses associated with the retinal input.

PMID- 7637868
TI  - Transforming growth factor-alpha immunoreactivity in the developing and adult
      brain.
AB  - Transforming growth factor-alpha immunoreactivity is examined in the developing
      and adult brain of cats and rats, and in the adult human brain in cryostat
      sections immediately processed free-floating with a well-characterized monoclonal
      antibody which does not cross-react with epidermal growth factor. Transforming
      growth factor-alpha immunoreactivity is observed in neurons of the cerebral
      neocortex, subiculum, hippocampus, striatum, thalamus, amygdala, basal forebrain,
      mesencephalon, cerebellar cortex, dentate nucleus and brainstem during
      development and in adulthood. The intensity of the immunoreaction directly
      correlates with the size of the cytoplasm. Diffuse transforming growth factor
      alpha immunoreactivity also occurs in the white matter of the cerebrum,
      cerebellum and brainstem in the kitten, but not in the adult cat. In addition to
      neurons, numbers of glial cells in the cerebellar white matter, brainstem and
      cerebral hemispheres during development, and a few glial cells in the cerebellar
      cortex, diencephalon, cerebral cortex and white matter in adults are strongly
      transforming growth factor-alpha immunoreactive. These results support the
      concept that transforming growth factor-alpha is widely distributed in the brain
      of mammals, localizes in both neurons and glial cells, and is development
      dependent. These findings also suggest that transforming growth factor-alpha may
      play a role in the developing and adult central nervous system.

PMID- 7637869
TI  - Chronic L-DOPA treatment differentially regulates gene expression of glutamate
      decarboxylase, preproenkephalin and preprotachykinin in the striatum of 6
      hydroxydopamine-lesioned rat.
AB  - The effect of a unilateral 6-hydroxydopamine lesion of the medial forebrain
      bundle in rats and subsequent L-DOPA treatment for eight weeks on
      preproenkephalin, preprotachykinin and glutamate decarboxylase (M(r) 67,000) gene
      expression in the striatum was investigated by in situ hybridization. A 6
      hydroxydopamine lesion of the medial forebrain bundle markedly increased the
      level of preproenkephalin messenger RNA (+66%) and modestly elevated the level of
      glutamate decarboxylase (M(r) 67,000) messenger RNA (+36%) in the denervated
      striatum, but caused a decrease in the level of preprotachykinin messenger RNA (
      54%) relative to the intact striatum and to sham-lesioned control animals.
      Treatment with L-DOPA (200 mg/kg/24 h) for eight weeks reduced but did not
      abolish the 6-hydroxydopamine lesion-induced elevation of preproenkephalin
      messenger RNA and slightly reduced the elevation of glutamate decarboxylase (M(r)
      67,000) messenger RNA in denervated striatum relative to intact side and control
      groups. However, L-DOPA treatment almost completely reversed the decrease in
      preprotachykinin messenger RNA caused by 6-hydroxydopamine lesioning when
      compared to intact side and control groups. The effect of L-DOPA on the gene
      expression of preproenkephalin and glutamate decarboxylase (M(r) 67,000) differs
      from the increase in striatal enkephalin content and glutamate decarboxylase
      activity previously found following L-DOPA treatment. In contrast, L-DOPA
      reversed the changes in preprotachykinin messenger RNA, reflecting previously
      reported increases in substance P content. The findings provide new evidence that
      chronic L-DOPA treatment differentially affects direct striatonigral and indirect
      striatopallidal pathways at the molecular level.

PMID- 7637870
TI  - Oriented growth of regenerating axons in axolotl forelimbs is consistent with
      guidance by diffusible factors from distal nerve stumps.
AB  - Previous studies have shown that when peripheral nerves in axolotl limbs are cut
      and surgically misdirected, regenerating axons grow back to the original pathways
      and innervate their correct muscles. In the present study however, we demonstrate
      that when given a choice between their correct nerve stump and an incorrect stump
      (forearm flexor nerve), regenerating extensor cranialis nerve axons grow towards
      both pathways. This result suggests that the directed growth of regenerating
      axons in the peripheral nervous system may be in response to factor(s) released
      from the distal nerve stumps, but that in this region of the limb, axons were
      unable to differentiate between correct and incorrect pathways. Growing axons
      appeared to be accompanied by neural sheath cells, whilst activated macrophages
      remained near the cut nerve stumps. Possible mechanisms by which regenerating
      axons may eventually innervate their correct targets are discussed.

PMID- 7637871
TI  - Presence and effects of pituitary adenylate cyclase activating peptide in the
      submandibular gland of the ferret.
AB  - Pituitary adenylate cyclase activating peptide (PACAP), a recently described
      vasoactive intestinal peptide-like neuropeptide, was found to be present in
      neurons in the submandibular gland of the ferret, where PACAP-immunoreactive
      nerve fibers were distributed around blood vessels, acini and ducts. Most of the
      PACAP-immunoreactive fibres were distinct from those storing vasoactive
      intestinal peptide. PACAP occurs in tissues as PACAP1-38 and PACAP1-27. PACAP1-38
      and PACAP1-27 but not PACAP16-38 displayed biological activity with about the
      same potency. They exerted vasodilator effects on the submandibular vasculature,
      which resulted in a greater fall in vascular resistance than an equimolar dose of
      vasoactive intestinal peptide. The vasodilator response was independent of
      muscarinic receptor activation. Neither vasoactive intestinal peptide nor PACAP
      alone evoked any flow of saliva. However, both vasoactive intestinal peptide and
      PACAP enhanced the fluid response to acetylcholine, and the flow of saliva as
      well as the output of protein in response to parasympathetic nerve stimulation,
      vasoactive intestinal peptide being more potent than PACAP. In vitro, protein was
      released from submandibular gland tissue in response to both vasoactive
      intestinal peptide and PACAP, vasoactive intestinal peptide being more potent
      than PACAP. PACAP (and vasoactive intestinal peptide) exerted its in vitro effect
      following adrenoceptor and muscarinic blockade and following degeneration of
      sympathetic nerves. Sympathetic denervation combined with parasympathetic
      preganglionic denervation resulted in supersensitivity to both vasoactive
      intestinal peptide and PACAP. The fact that PACAP and vasoactive intestinal
      peptide occur in different nerve fibre populations suggests different roles for
      the two peptides in the submandibular gland.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7637872
TI  - Localization of glucose transporter GLUT 3 in brain: comparison of rodent and dog
      using species-specific carboxyl-terminal antisera.
AB  - The carboxyl-terminal amino acid sequences of the canine and gerbil glucose
      transporter GLUT3 were determined and compared to the published rat sequence.
      Eleven of 16 amino acids comprising the carboxyl terminus of GLUT3 were found to
      be identical in rat and dog. However, the canine sequence "ATV" substitutes for
      the rat sequence "PGNA" at the end of the molecule. The gerbil sequence has 12 of
      16 amino acids identical to the rat, including the PGNA terminus. Based on these
      sequences, four peptides were synthesized, and two polyclonal antisera (one to
      the canine sequence and one to the rat sequence) were raised to examine the
      distribution of GLUT3 in canine and rodent brain. Immunoblots of brain membrane
      preparations showed that both antisera identified peptide-inhibitable protein
      bands of molecular weight 45,000-50,000. Immunocytochemical studies demonstrated
      that binding sites for these antisera were abundantly distributed in neuropil in
      all brain regions. Areas rich in synapses and areas surrounding microvessels
      exhibited especially high reactivity. GLUT3 reactivity was similarly distributed
      in canine and rodent brain, except at the blood-brain barrier. GLUT3 was not
      detected in the blood-brain barrier in gerbil and rat but was present in many
      canine cerebral endothelial cells, particularly in cerebellum and brain stem. The
      carboxyl-terminal antisera employed in this study exhibited high degrees of
      species specificity, indicating that the three or four terminal amino acids of
      the immunizing peptides (ATV and PGNA) are important epitopes for binding the
      polyclonal antibodies. These antisera exhibited only minimal binding to brain
      tissue of non-target species, yet yielded similar staining patterns in neuropil
      of rodent and canine brain. This finding provides strong evidence that the
      observed staining patterns accurately reflect the distribution of GLUT3 in brain.
      In addition, the presence of vascular GLUT3 in dog brain suggests that the canine
      blood-brain barrier may be preferable to that of the rat as a model for studies
      of glucose transport relevant to human brain.

PMID- 7637873
TI  - Chronic blockade of muscarinic cholinergic receptors by systemic trihexyphenidyl
      (Artane) administration modulates but does not mediate the dopaminergic
      regulation of striatal prepropeptide messenger RNA expression.
AB  - A striatal dopaminergic denervation leads to changes in the expression of
      messenger RNA encoding prepropeptides contained in striatal efferent neurons.
      Such a dopaminergic lesion also abolishes a functional equilibrium between
      dopaminergic and cholinergic transmissions, generally believed to operate within
      the neostriatum, which constitutes the theoretical basis for the clinical use of
      antimuscarinic drugs in extrapyramidal diseases. It is possible, therefore, that
      changes in prepropeptide messenger RNA expression are mediated by an alteration
      in cholinergic transmission. To test this hypothesis, we have examined in rats
      whether trihexyphenidyl, an antimuscarinic drug of wide clinical use, can
      counteract the changes in preproenkephalin, preprotachykinin and preprodynorphin
      messenger RNA expression produced by a unilateral 6-hydroxydopamine lesion of
      substantia nigra dopaminergic neurons. Two weeks after the lesion,
      trihexyphenidyl was continuously administered through an osmotic minipump (5
      mg/day for 15 days) to half of the lesioned and sham-operated rats, the other
      half receiving the vehicle. Using quantitative in situ hybridization
      histochemistry, messenger RNAs were analysed at two rostrocaudal levels (anterior
      and central) of the neostriatum. In parallel, M1 muscarinic receptors were
      measured by autoradiography of [3H]pirenzepine binding sites. In sham-operated
      rats, trihexyphenidyl administration produced a significant increase (17-27%) in
      M1 binding sites. In addition, preproenkephalin messenger RNA levels were
      decreased (-38%) in the central part, while preprodynorphin messenger RNA levels
      were significantly increased (+22%) at both striatal levels. In 6-hydroxydopamine
      lesioned rats, the expected changes in messenger RNAs were observed when ipsi-
      versus contralateral side values were compared, but changes were not always
      detected when comparison was established between values from the dopamine
      denervated neostriatum and those from sham-operated rats. The trihexyphenidyl
      administration in 6-hydroxydopamine-lesioned animals was unable to reproduce the
      up-regulation of M1 receptors, even in the intact neostriatum. This
      antimuscarinic treatment further increased preproenkephalin messenger RNA levels
      in the denervated anterior neostriatum, amplifying the ipsi- versus contralateral
      difference. It also potentiated the imbalance in preprotachykinin messenger RNA
      expression, mainly as a result of an increase of preprotachykinin messenger RNA
      levels in the intact neostriatum. In contrast, trihexyphenidyl treatment by
      increasing preprodynorphin messenger RNA in both neostriata abolished the ipsi-
      versus contralateral difference observed in lesioned rats. In conclusion, with
      the exception of preprodynorphin messenger RNA, trihexyphenidyl treatment was
      unable to counteract the imbalance in prepropeptide messenger RNA expression
      produced by a unilateral striatal dopaminergic denervation and even amplified
      this effect. These results question the neostriatum as the site of action of
      antimuscarinic drugs in producing their therapeutic effect in extrapyramidal
      syndromes.

PMID- 7637874
TI  - Enhancement of morphine analgesia by the alpha 2-adrenergic antagonist yohimbine.
AB  - Although interactions between opioids and adrenergic agonists in the treatment of
      pain have been demonstrated in humans, the contribution of specific adrenergic
      receptors in this interaction remains to be clarified. In a double-blind, placebo
      controlled study in male patients with postoperative dental pain, we investigated
      the effect of preoperative administration of the alpha 2-adrenergic antagonist,
      yohimbine, on analgesia produced by postoperative intravenous morphine. Although
      yohimbine by itself did not affect the pain, the overall analgesic effect of
      morphine was significantly enhanced in the presence of yohimbine. This report is
      the first to demonstrate that an alpha 2-adrenergic antagonist enhances opiate
      analgesia in humans.

PMID- 7637875
TI  - Intrastriatal and intrasubthalamic stimulation of metabotropic glutamate
      receptors: a behavioral and Fos immunohistochemical study.
AB  - Prior work has shown that intrastriatal injection of the metabotropic glutamate
      receptor agonist 1S,3R-ACPD results in pronounced contralateral rotation, and the
      basis for this effect is thought to be increased activity of dopaminergic
      nigrostriatal neurons. We tested this hypothesis by determining the expression of
      Fos-like immunoreactivity after intrastriatal injection of 1S,3R-ACPD. Intense
      Fos-like immunoreactivity was noted in the globus pallidus, entopeduncular
      nucleus, subthalamic nucleus and substantia nigra pars reticulata. Ablation of
      the subthalamic nucleus 10 days prior to intrastriatal injection of 1S,3R-ACPD
      abolished rotational behaviour but not Fos-like immunoreactivity in the globus
      pallidus, entopeduncular nucleus and substantia nigra. Intrasubthalamic injection
      of 1S,3R-ACPD produced marked contralateral rotation and a pattern of Fos-like
      immunoreactivity similar to that seen after intrastriatal 1S,3R-ACPD injection.
      These results suggest that stimulation of striatal metabotropic glutamate
      receptors inhibits striatal projection neuron activity, while stimulation of
      subthalamic metabotropic glutamate receptors increases subthalamic nucleus
      activity. Increased subthalamic nucleus activity is necessary and sufficient for
      the expression of rotational behavior. These results also suggest that
      metabotropic glutamate receptor antagonists may be useful in the treatment of
      Parkinson's disease.

PMID- 7637876
TI  - Glutamate decarboxylase messenger RNA in rat pallidum: comparison of the effects
      of haloperidol, clozapine and combined haloperidol-scopolamine treatments.
AB  - We have investigated the effects of neuroleptic treatments which do, or do not,
      induce catalepsy on the level of expression of glutamate decarboxylase, the rate
      limiting enzyme in GABA synthesis, in efferent neurons of the pallidum in adult
      rats. Different regimens of haloperidol (1 mg/kg s.c., three, seven or 14 days; 2
      mg/kg, s.c., 10 days) induced catalepsy in a majority of rats and increased
      glutamate decarboxylase messenger RNA levels in the globus pallidus (external
      pallidum) in those rats exhibiting catalepsy. Levels of glutamate decarboxylase
      messenger RNA were also increased in the entopeduncular nucleus (internal
      pallidum), but only after 14 days of treatment with haloperidol. The atypical
      antipsychotic clozapine (seven days, 20 mg/kg, s.c.), which did not induce
      catalepsy, slightly decreased glutamate decarboxylase messenger RNA levels in the
      globus pallidus. When co-administered with haloperidol (seven days, 1 mg/kg
      s.c.), the muscarinic antagonist scopolamine (1 mg/kg, s.c.) completely blocked
      both haloperidol-induced catalepsy and increases in glutamate decarboxylase
      messenger RNA levels in the globus pallidus. In contrast, scopolamine was not
      able to block increased glutamate decarboxylase and enkephalin messenger RNA
      expression induced by haloperidol in the striatum. These results reveal a good
      correlation between increases in glutamate decarboxylase messenger RNA levels in
      the globus pallidus and catalepsy after these drug treatments and suggest that
      anticholinergic blockade of the behavioral and molecular effects of neuroleptics
      may involve non-striatal mechanisms.

PMID- 7637877
TI  - Increases in hippocampal and frontal cortical acetylcholine release associated
      with presentation of sensory stimuli.
AB  - In vivo microdialysis was employed to monitor acetylcholine release in the
      hippocampus and frontal cortex of freely behaving rats. Four stimuli were
      presented on separate occasions in the course of a dialysis session to rats with
      microdialysis probes implanted in the hippocampus or frontal cortex. Visual,
      auditory, olfactory and tactile stimuli elicited a number of different responses
      such as exploratory and consummatory behaviours. Presentation of two of the
      stimuli (auditory and tactile) also produced periods of alert immobility
      (freezing). All of the stimuli increased acetylcholine release in both the
      hippocampus and cortex: in the hippocampus, this increase was statistically
      significant with all except the olfactory stimulus, whereas in the cortex all but
      the visual stimulus resulted in significant increases. In the hippocampus, there
      were no significant differences between the increases in acetylcholine release
      produced by the four stimuli. In contrast, in the cortex, there was significant
      variation between the magnitude of acetylcholine release produced by the
      different stimuli: acetylcholine release elicited by tactile stimulation was
      greater than that produced by the other stimuli. There was no significant
      variation in the duration of increases in acetylcholine release produced by the
      stimuli in either the hippocampus or cortex. These results provide evidence that
      acetylcholine release is associated with a variety of behavioural responses to
      stimuli designed to produce arousal, and point to a role for cortical and
      hippocampal cholinergic mechanisms in arousal or attention. Further, the results
      suggest that under some circumstances cortical and hippocampal acetylcholine
      release may be regulated differentially.

PMID- 7637878
TI  - Reduction of GABA-mediated inhibitory postsynaptic potentials in hippocampal CA1
      pyramidal neurons following oral flurazepam administration.
AB  - Oral administration of the benzodiazepine, flurazepam, for one week results in
      tolerance in vivo and in vitro and in a reduction in recurrent and feedforward
      inhibition in vitro in the CA1 pyramidal cell region of hippocampus. In the
      present study CA1 pyramidal cells were examined intracellularly in vitro in rat
      hippocampal slices (500 microns) from rats sacrificed two or seven days after
      cessation of oral flurazepam treatment. Following drug treatment, the membrane
      characteristics of CA1 pyramidal cells were not significantly different from
      control neurons. GABAA-mediated, early inhibitory postsynaptic potentials were
      significantly reduced in amplitude (60%) in pyramidal neurons from rats killed
      two days, but not in those killed seven days, after the end of drug
      administration. The decrease in early inhibitory postsynaptic potential amplitude
      was observed using just-subthreshold, threshold and supramaximal orthodromic
      stimulation as well as following antidromic activation. The magnitude of the
      decrease in the early inhibitory postsynaptic potential amplitude was similar in
      the presence of the GABAB antagonist, CGP 35348, and could not be attributed to
      differences in the strength of afferent stimulation between flurazepam-treated
      and control groups. The size of the GABAB-mediated, late inhibitory postsynaptic
      potentials was also significantly decreased (45%) in comparison to control cells.
      Reversal potentials for both the early (-72 mV) and late (-92 mV)
      hyperpolarizations were not significantly different between groups. Following
      high intensity orthodromic stimulation, in the presence of an intracellular
      sodium channel blocker (QX-314) which also blocks the GABAB-mediated late
      hyperpolarization, a bicuculline-sensitive late depolarizing potential was
      unmasked in neurons from FZP-treated rats, but never from control cells.
      Excitatory postsynaptic potential amplitude was significantly increased in
      flurazepam-treated neurons and the threshold for the synaptically-evoked action
      potential was significantly increased. Following depolarizing current injection,
      the duration and frequency of pyramidal cell discharges and the action potential
      threshold were not altered by oral flurazepam treatment. The amplitude of the
      fast afterhyperpolarization was also not changed. Overall, the findings indicate
      an impairment of transmission at GABAergic synapses onto hippocampal CA1
      pyramidal cell neurons after chronic benzodiazepine treatment at a time when rats
      are tolerant to the anticonvulsant effects of the benzodiazepines in vivo.

PMID- 7637879
TI  - Induction of rapid eye movement sleep by the microinjection of nerve growth
      factor into the pontine reticular formation of the cat.
AB  - Nerve growth factor is an endogenous protein which belongs to the neurotrophin
      family of trophic factors. According to the neurotrophic hypothesis,
      neurotrophins are synthetized by target tissues and regulate the survival and
      phenotype of their innervating neurons. Whereas these trophic molecules have been
      mainly thought to be involved in developmental processes, their existence in the
      central nervous system of the adult animal suggests that they may play a role in
      neuronal physiology. Recently, it has been reported that neurons that express
      messenger RNA for two neurotrophins, namely brain-derived neurotrophic factor and
      neurotrophin-3, are located medial to the locus coeruleus and ventral to the
      fourth ventricle. This area corresponds to the latero-dorsal tegmental nucleus,
      which contains cholinergic neurons that have been implicated in the generation of
      rapid eye movement sleep. In turn, the laterodorsal tegmental nucleus is
      reciprocally connected with the nucleus pontis oralis in the rostrodorsal pontine
      reticular formation, which is an area that is involved in the initiation of the
      physiological patterns of activity that define the state of rapid eye movement
      sleep. Scattered neurons in the nucleus pontis oralis express the low-affinity
      nerve growth factor receptor which also binds the other neurotrophins with
      similar affinity. In addition, neurons in the area of the nucleus pontis oralis
      have been reported to express a subtype of the neurotrophin high affinity
      receptors. These membrane receptors, independently or in combination with the low
      affinity receptors, have been proposed to mediate the delayed, long-term effects
      of neurotrophins.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7637880
TI  - Block of the N-methyl-D-aspartate receptor by phencyclidine-like drugs is
      influenced by alternative splicing.
AB  - N-Methyl-D-aspartate (NMDA) receptors were expressed in Xenopus oocytes from
      injected mRNA. The presence of an alternatively-spliced insertion encoding 21
      amino acids at the N-terminus of the NMDAR1 (NR1(111)) subunit, made homomeric
      assemblies of the receptor more sensitive to ketamine and MK-801 than receptors
      assembled from NMDAR1 subunits lacking this insert (NR1(011) and NR1(001)). The
      influence of this insert was maintained when NR1 subunits were co-expressed in
      heteromeric combinations with NR2B. The increased sensitivity of the receptors
      containing the insert (NR1(111)) was accompanied by a faster on-rate for drug
      action than was observed for receptors lacking the insert (NR1(011) and
      NR1(001)). Our results suggest that the action of phencyclidine-like drugs is
      influenced by the presence of Insertion I in the NMDA isoforms, generated by
      alternative splicing.

PMID- 7637881
TI  - Reduction of substance P binding sites in the spinal dorsal horn after perineural
      capsaicin treatment in the rat.
AB  - The long-term effect of perineural capsaicin treatment on the distribution of
      substance P (SP) binding sites was studied in the rat spinal dorsal horn using
      125I-labelled Bolton-Hunter-SP. Three months after local application of capsaicin
      onto the sciatic nerve quantitative evaluation of the autoradiograms revealed a
      significant decrease in the density of SP binding sites of up to 48% in regions
      of laminae I and II of the spinal dorsal horn somatotopically related to the
      capsaicin treated sciatic nerve. It is suggested that reduction in SP binding may
      result from transganglionic and transsynaptic degenerative changes affecting
      postsynaptic structures. Changes in the distribution of SP binding sites may
      significantly contribute to functional alterations observed after perineural
      treatment with capsaicin.

PMID- 7637882
TI  - Preganglionic sympathetic neurones, innervating the guinea pig adrenal medulla,
      immunohistochemically contain choline acetyltransferase and also leu-enkephalin.
AB  - Applying retrograde neuronal tracing combined with double labelling
      immunofluorescence, preganglionic nerve cell bodies in the intermediate grey
      matter of the guinea pig thoracic spinal cord, projecting to the adrenal gland,
      co-exhibited immunolabelling for choline-acetyltransferase (ChAT) and sometimes,
      also for leu-enkephalin. Likewise, ChAT-immunoreactive nerve fibres, forming a
      dense meshwork in the adrenal medulla, partly contained immunostaining also for
      leu-enkephalin. Some of the intramedullary nerve cell bodies were ChAT-positive
      but were non-reactive for leu-enkephalin. The findings provide evidence for an
      extrinsic (preganglionic) and an intrinsic (postganglionic) cholinergic nerve
      system in the guinea pig adrenal medulla, the preganglionic system utilising leu
      enkephalin as co-mediator.

PMID- 7637883
TI  - Axonal constriction at Ranvier's node increases during development.
AB  - We have studied the ratio between the nodal and the internodal diameter (the
      dn/d(in) ratio) of large myelinated axons in the L7 ventral spinal root of the
      cat during pre- and postnatal development using light and electron microscopy. A
      substantial nodal constriction, dn/d(in) = 0.6, was found at the beginning of
      myelination, about 2 weeks before birth. The ratio decreased during the
      subsequent 10 weeks and approached the adult value of 0.47 (SE 0.01, N = 45) in
      the 8 weeks old kitten. The observations are discussed with respect to the
      maturation of the nodal region and to our earlier idea that the constricted nodal
      axon segments of large peripheral myelinated nerve fibres of adult cats and
      kittens 2 months and more of age are sites capable of interacting with and
      perhaps even controlling the passage of axonally transported materials.

PMID- 7637884
TI  - Localisation of dopamine D3 receptor in the rat cerebellar cortex: a light
      microscope autoradiographic study.
AB  - The pharmacological properties and the anatomical localisation of dopamine D3
      receptor were assessed in the rat cerebellar cortex using radioligand binding
      techniques associated with light microscope autoradiography and 7-[3H]hydroxy-N,N
      di-n-propyl-2-aminotetralin (7-[3H]OH-DPAT) as a ligand. 7-[3H]OH-DPAT was
      specifically bound to sections of rat cerebellar cortex with a dissociation
      constant (Kd) of 0.5 nM and a maximum density of binding sites (Bmax) of 97 +/- 4
      fmol/mg tissue. The rank order of potency of competitors of 7-[3H]OH-DPAT binding
      and the observation that guanosine triphosphate did not affect radioligand
      binding suggest the labelling of a dopamine D3 receptor. 7-[3H]OH-DPAT binding
      sites are located mainly in the molecular layer and in lesser amounts in the
      Purkinje neuron layer, primarily within the cell body of Purkinje neurons. No
      specific accumulation of silver grains was observed in the granule neuron layer
      or in the white matter of the cerebellar cortex. The localisation of a putative
      dopamine D3 receptor within Purkinje neurons suggests that this site may have
      functional relevance in the cerebellar cortex.

PMID- 7637885
TI  - Modulation by adenosine of a neuronal inhibitory interaction in the rat
      hippocampus.
AB  - Adenosine is acknowledged to have a primarily inhibitory function in the central
      nervous system, but is believed to have little effect on inhibitory neurones
      themselves. It is, however, difficult to determine the effect of adenosine on
      inhibitory synaptic potentials since adenosine directly depresses evoked
      potentials and, in the presence of bicuculline to block GABAA-mediated
      inhibition, the bicuculline-resistant fraction of paired-pulse inhibition (ppi)
      is greater between pairs of small potentials than between pairs of larger
      potentials. Here, adenosine increased bicuculline-resistant ppi when stimulus
      strength was constant between adenosine and control but ppi of responses in
      adenosine was markedly less than ppi of control responses of the same size.
      Adenosine had less effect on the size of 'conditioned' potentials than on control
      potentials. It is concluded that adenosine can reduce the bicuculline-resistant
      fraction of paired-pulse inhibition in the hippocampus. Further quantitative
      comparison of the effects of adenosine on ppi and on single evoked potentials
      excluded a difference in the potency of adenosine at excitatory and inhibitory
      terminals as an explanation for this activity. The results suggest that adenosine
      may diminish bicuculline-resistant paired-pulse inhibition by enhancing a
      simultaneous facilitatory component of the neuronal responses.

PMID- 7637886
TI  - Behavioral evidence of thermal hyperalgesia in non-obese diabetic mice with and
      without insulin-dependent diabetes.
AB  - The non-obese diabetic (NOD) mouse, a model of Type 1 diabetes in humans, has
      proven useful for the study of genetic, immunologic and epidemiologic aspects of
      inherited diabetes. Behavioral evidence of hyperalgesia may also be present in
      the NOD mouse but has not been described. This study examined NOD mice with
      (NOD+) and without (NOD-) insulin-dependent diabetes, and control strain (ILI)
      mice for evidence of hyperalgesia to a noxious thermal stimulus. Interestingly,
      both NOD+ and NOD- mice showed reduced mean hindpaw withdrawal latencies when
      compared with non-diabetic ILI mice. NOD+ and NOD- mice were also abnormal in
      their general appearance, activity level, posture, gait and muscle bulk when
      compared with ILI mice. These findings raise the possibility that hyperalgesia in
      insulin-dependent NOD mice, or insulin-dependent humans with Type 1 diabetes, may
      be independent of diabetes and due to a primary disturbance within sensory
      pathways.

PMID- 7637887
TI  - A comparison of the leech Theromyzon tessulatum angiotensin I-like molecule with
      forms of vertebrate angiotensinogens: a hormonal system conserved in the course
      of evolution.
AB  - After five steps of purification including gel permeation, anti-angiotensin I
      affinity column chromatography followed by reverse-phase HPLC, a peptide
      immunoreactive to two different antisera (anti-angiotensin II and anti
      angiotensin I) was purified to homogeneity from extracts of the leech Theromyzon
      tessulatum. The first 14 amino acid residues of the purified peptide
      (DRVYIHPFHLLXWG) established by automated Edman degradation, reveal the existence
      in leeches of an angiotensin I-like molecule close to human angiotensin I. The
      sequence of the purified peptide presents 78.5% of homology with the N-terminal
      part of human angiotensinogen. Moreover, in its sequence, this peptide presents
      the cleavage sites of vertebrate angiotensin metabolic enzymes, i.e. the renin
      and the angiotensin-converting enzyme. This finding constitutes the first
      biochemical characterization of an angiotensin I in Invertebrates. It also
      reflects the high conservation of angiotensins in the course of evolution,
      suggesting a fundamental role of this family in fluid homeostasis.

PMID- 7637888
TI  - Low potency inhibition of Ca2+ channel currents in human neuroblastoma (SH-SY5Y)
      cells by [Ala31]NPY, an L-alanine substituted analogue of neuropeptide Y.
AB  - Whole-cell Ca2+ channel currents were recorded in human neuroblastoma (SH-SY5Y)
      cells, using the perforated-patch technique with 10 mM Ba2+ as charge carrier.
      Neuropeptide Y (NPY; 10 nM to 1 microM) caused concentration-dependent inhibition
      of Ca2+ channel currents which were associated with a slowing in current
      activation kinetics. [Ala31]NPY, a residue 31 L-alanine substituted analogue of
      NPY, also inhibited Ca2+ channel currents and caused slowing of activation
      kinetics, but with approximately 6-fold lower potency. In the presence of 100 nM
      [Ala31]NPY (which itself had little or no effect on currents), the actions of NPY
      were similar in magnitude to its effects in the absence of the analogue. Our
      results suggest that substitution of isoleucine for alanine at residue 31 results
      in a NPY analogue which is a full agonist but with lower affinity for Y2
      receptors.

PMID- 7637889
TI  - Evidence for a mesolimbic pathway in anuran amphibians: a combined tract
      tracing/immunohistochemical study.
AB  - The aim of the present study was to determine whether a dopaminergic mesolimbic
      pathway, as found in the brain of amniotes, also exists in anuran amphibians. For
      that purpose, application of retrograde tracers in the nucleus accumbens of Rana
      perezi was combined with tyrosine hydroxylase immunohistochemistry. Double
      labeled cells were found in the dorsomedial part of the posterior tubercle and,
      more frequently, in the midbrain tegmentum. It may be concluded, therefore, that
      a dopaminergic mesolimbic pathway does exist in amphibians. Nevertheless, the
      organization of the ventral (mesolimbic) and dorsal parts of the mesostriatal
      connections seems to vary from a caudal-to-rostral arrangement in amphibians to a
      medial-to-lateral arrangement in amniotes.

PMID- 7637890
TI  - Suppressive effect of vasopressin on the hyperglycemic response to intracranial
      injection of 2-deoxy-D-glucose.
AB  - Vasopressin (VP) is a peptide consisting of 9 amino acids which acts as a
      neurotransmitter or neuromodulator in the central nervous system. Neurons
      containing VP project to some nuclei in the hypothalamus that have a role in
      energy metabolism. To clarify the possible role of VP on glucose metabolism in
      the brain, we examined the effect of intracranial injection of VP on the
      hyperglycemia induced by 2-deoxy-D-glucose (2DG) and obtained the following
      results. The hyperglycemic and hyperglucagonemic responses induced by 2DG were
      significantly suppressed and enhanced by co-injections of VP and a VP-antagonist
      with 2DG, respectively. However, co-injections of either VP or a VP-antagonist
      with 2DG had no effect on the change in plasma insulin concentration. These
      findings suggest that central VP plays a suppressive role in the hyperglycemic
      and hyperglucagonemic responses to 2DG.

PMID- 7637891
TI  - Complex involvement of nitric oxide and cGMP at N-methyl-D-aspartic acid
      receptors regulating gamma-[3H]aminobutyric acid release from striatal slices.
AB  - Whilst the depolarization of postsynaptic N-methyl-D-aspartic acid (NMDA)
      receptors leads to an influx of Ca2+ and subsequent synthesis of nitric oxide
      (NO), we examined roles for NO at striatal NMDA receptors regulating transmitter
      release. In superfused rat striatal slices, NMDA-evoked release of gamma
      [3H]aminobutyric acid ([3H]GABA) was investigated in the presence of nitrergic
      drugs. NMDA-induced release of [3H]GABA was attenuated by D-2
      aminophosphonopentanoate, tetrodotoxin and omission of Ca2+. L-Arginine enhanced
      NMDA-evoked release of [3H]GABA, but exogenous NO donors were ineffective.
      Inhibitors of NO synthase (NG-nitro- and NG-amino-L-arginine) and guanylate
      cyclase (LY83583) elevated release. Since NMDA-evoked release of [3H]GABA was
      partially tetrodotoxin-sensitive, nitrergic-linked NMDA receptors regulating the
      release are both pre- and extrasynaptic. Thus not only does NO arise from
      multiple sites, and involve NMDA receptors with their redox site insensitive to
      exogenous NO donors, but the NMDA receptors are under the influence of nitrergic
      and cGMP-linked negative feedback mechanisms.

PMID- 7637892
TI  - Differences in mossy fibre sprouting during conventional and rapid amygdala
      kindling of the rat.
AB  - The effect of conventional and rapid amygdala kindling on mossy fibre sprouting
      and on the development of secondary after-discharges in the hippocampus, i.e.
      recurring after-discharges after the end of primary after-discharges in the
      amygdala, was investigated. Rapid kindling, i.e. electric stimulation of the
      amygdala for 10 s every 30 min, induced prolonged secondary after-discharges in
      the hippocampus, which occurred after the first stimulation, and mossy fibre
      sprouting. Conventional kindling, i.e. electric stimulation of the amygdala for 1
      s once daily, induced secondary after-discharges in the hippocampus only after
      prolonged motor seizures, but no mossy fibre sprouting. These results suggest
      that mossy fibre sprouting and the occurrence of secondary after-discharges in
      the hippocampus are not crucial for conventional amygdala kindling. Rapid
      kindling induces these epileptogenic changes in the hippocampus very early and
      may therefore follow a different route of epileptogenesis than conventional
      kindling.

PMID- 7637893
TI  - Intracarotid hypothermic saline infusion: a new method for reversible blood-brain
      barrier disruption in anesthetized rats.
AB  - An animal model for reversible blood-brain barrier disruption has been developed.
      Retrograde infusion of hypothermic saline solution (8 +/- 1 degree C) into the
      left external carotid artery of normothermic, Wistar rats reversibly increases
      cerebrovascular permeability to Evans blue albumin in the left cerebral
      hemisphere. Isotonic saline solutions at 37 degrees C for Group I and at 8 +/- 1
      degree C for Group II were infused for 30 s at a constant rate of 0.12 ml/s into
      the left external carotid artery. Evans blue, the barrier tracer, was
      administered intravenously either prior to or at intervals 5, 30, 180, 360 min
      after the hypothermic saline infusion under pentobarbital anesthesia. All animals
      receiving hypothermic saline perfusion had disturbed blood-brain barrier
      permeability. Based on visual inspection, disruption grade in the left
      hemispheres of 10 of 16 animals was 3+. Mean values for Evans blue dye were found
      to be 0.32 +/- 0.08 mg% in left the hemisphere after normothermic saline infusion
      (Group 1), and 2.9 +/- 0.4 mg% in the same hemisphere after hypothermic saline
      infusion (Group II). The difference was found to be significant between Group I
      and Group II (P < 0.001). The increase in cerebrovascular permeability was
      temporary, however, although Evans blue albumin extravasion remained slightly
      elevated 3 h after infusion, it was normal 6 h after infusion.

PMID- 7637894
TI  - Microanatomical and electrophysiological changes of the rat dentate gyrus caused
      by lesions of the nucleus basalis magnocellularis.
AB  - The effect of unilateral or bilateral lesions of the nucleus basalis
      magnocellularis (NBM) on the dentate gyrus of the hippocampus were assessed using
      microanatomical and electrophysiological techniques. NBM is the main cholinergic
      basal forebrain nucleus that supplies the fronto-parietal cortex. Lesions were
      induced using the neurotoxin ibotenic acid or a radio-frequency system and did
      not affect glutamic acid decarboxylase activity both in the frontal cortex and in
      the hippocampus. At 4 weeks after lesioning, a loss of choline acetyltransferase
      (ChAT) activity and of ChAT-immunoreactive fibres was observed in the frontal
      cortex but not in the hippocampus and no changes in the density of granule
      neurons of the dentate gyrus or in the hippocampal long-term potentiation (LTP)
      were noticeable. At 8 weeks after lesioning the loss of both ChAT activity and of
      ChAT-immunoreactive fibres persisted in the frontal cortex of NBM-lesioned rats.
      Moreover, at this time a significant decrease in the density of granule neurons
      in the dentate gyrus accompanied by a reduced probability of dentate LTP
      induction were observed in both ibotenic acid- and radio-frequency-lesioned rats.
      These findings have shown that although NBM does not send direct cholinergic
      projections to the hippocampus, lesions of this cholinergic nucleus are
      accompanied by delayed neurodegenerative changes involving the dentate gyrus.
      This suggests the occurrence of indirect connections between NBM and the
      hippocampus, the functional relevance of which should be explored.

PMID- 7637895
TI  - Diethyldithiocarbamate, a superoxide dismutase inhibitor, counteracts the
      maturation of ischemic-like lesions caused by endothelin-1 intrastriatal
      injection.
AB  - The effects of a focal lesion induced by endothelin-1 (ET-1, 0.8 microgram/0.8
      microliter) on superoxide dismutase (SOD) were studied in the neostriatum of male
      rats. SOD activity was analyzed at several time intervals (5, 20, 60 min, 4, 24 h
      and 7 days) after the lesion. No significant changes were observed early after
      the injection, but SOD activity started to rise significantly at the 60-min time
      interval reaching a peak 24 h after the injection. In a second experiment the
      volume of ET-1-induced lesion was evaluated following treatments which induce
      variations of SOD activity. ET-1 caused a large lesion (9.20 +/- 1.32 mm3) in the
      neostriatum 24 h after the injection that was 3-fold greater than that observed 1
      h after. Rats treated with the SOD inhibitor diethyldithiocarbamate showed a
      lesion equivalent to that observed 1 h after ET-1 injection, suggesting that SOD
      may be involved in the maturation of ET-1-induced neuronal damage.

PMID- 7637896
TI  - Quoting patients for the record.

PMID- 7637897
TI  - Assisting with chest tube removal.

PMID- 7637898
TI  - Caring for patients with pulmonary problems.

PMID- 7637899
TI  - Myths & facts ... about pressure ulcer care.

PMID- 7637900
TI  - Preventing footdrop when your patient's on the mend.

PMID- 7637901
TI  - Avoiding dehydration.

PMID- 7637902
TI  - Home infusion therapy. Shielding yourself from lawsuits.

PMID- 7637903
TI  - Patient-teaching aid. How to examine your breasts.

PMID- 7637904
TI  - Behind the locked door.

PMID- 7637905
TI  - Understanding oral infections.

PMID- 7637906
TI  - 18 tips for infection control at home.

PMID- 7637907
TI  - Gastric tonometry. A quicker way to evaluate tissue oxygenation.

PMID- 7637908
TI  - Heading off theophylline toxicity.

PMID- 7637909
TI  - Giving diuretics by continuous infusion.

PMID- 7637910
TI  - Gastrointestinal bleeding. Preventing hypovolemic shock.

PMID- 7637911
TI  - Hypertension: keeping dangerous blood pressure down.

PMID- 7637912
TI  - Elizabeth's marathon.

PMID- 7637913
TI  - Double trouble.

PMID- 7637915
TI  - The push is on: delivering medications safely by i.v. bolus.

PMID- 7637914
TI  - Resuscitation decisions: showing a family the way.

PMID- 7637916
TI  - Care paths: keeping patients on the right track.

PMID- 7637918
TI  - Defending your patient against nosocomial pneumonia.

PMID- 7637917
TI  - When a Jehovah's Witness refuses a transfusion.

PMID- 7637919
TI  - Teach your patients faster & better.

PMID- 7637920
TI  - Remembering Mrs. Finney. Looking back at a special nursing mentor.

PMID- 7637921
TI  - Ten dogs and a monkey.

PMID- 7637922
TI  - Human immunodeficiency virus infection in women in Auckland: an evolving
      epidemic.
AB  - AIMS: To study the epidemiology, presenting features and outcome of HIV infection
      among women in Auckland. METHODS: Retrospective review of the medical records of
      all HIV infected women cared for by the adult infectious disease unit or the
      sexual health clinic at Auckland Hospital up to the end of December, 1993.
      RESULTS: Thirty women with HIV infection were cared for between September 1986
      and December 1993. Heterosexual intercourse, often with a man from a country with
      endemic heterosexual HIV transmission, was the most common means of acquiring HIV
      infection. Late diagnosis of infection probably contributed to the brief median
      survival seen in the nine women who developed AIDS. CONCLUSIONS: Increased
      education is necessary to inform women about the risks of acquiring HIV
      infection. This education should encourage safer sexual behaviour and the use of
      needle exchange programmes to minimise the growth of this epidemic.

PMID- 7637923
TI  - Salt restriction and physical activity in treated hypertensives.
AB  - AIM: To determine the effect on blood pressure from brisk walking with or without
      salt restriction in a community based sample of treated hypertensives. METHODS:
      The intervention was undertaken in a community setting with a factorial
      randomised controlled trial and blinded assessment of blood pressure. One hundred
      and eighty one healthy adult volunteers with a sedentary lifestyle and on
      pharmacological therapy for hypertension briskly walked for 40 minutes three
      times per week with or without salt restriction. Systolic and diastolic blood
      pressure were assessed at three and six months. RESULTS: Of the original 208
      participants 181 (87%) completed the study. significant reductions of up to 7 mm
      Hg were found in systolic blood pressure at 3 months for brisk walking alone (p =
      0.04) and salt restriction alone (p = 0.03) but not for the combined intervention
      (p = 0.17). No significant change was found for diastolic blood pressure. There
      was no significant change in blood pressure at 6 months. CONCLUSIONS: Simple
      advice on exercise and sodium restriction in a community setting can
      significantly lower systolic blood pressure at least for 3 months. The
      combination of the two interventions was less effective than each therapy alone.

PMID- 7637924
TI  - Yersinia enterocolitica is a common cause of gastroenteritis in Auckland.
AB  - AIMS: Infections with Yersinia enterocolitica are a significant cause of
      gastroenteritis in many countries, However, little information is available on
      the incidence of human disease in New Zealand. A study was performed between
      January 1988 and December 1993 to investigate aspects of the epidemiology of
      yersiniosis in the Auckland region including prevalence, age and sex
      distribution, strain definition and seasonal occurrence. METHODS: Culture of 231
      128 faecal samples for enteric pathogens was performed at Diagnostic Laboratory,
      a community laboratory in Auckland, between January 1988 and December 1993. All
      yersinia isolates recovered were sent to the department of veterinary pathology
      and public health, Massey University for further typing. Relevant data were
      entered into a database and reviewed at the end of the study period. RESULTS:
      1469 of the samples, representing 941 cases, were positive for strains of
      yersinia during the study period, a crude isolation rate of 0.6%. A single strain
      from each of the cases was further typed and yersinia enterocolitica was found to
      constitute the majority of the isolates (918), making it the third most common
      enteric pathogen isolated after campylobacter and salmonella. Of the strains
      isolated, 98% were recognised human pathogens, with biotype 4, serotype 0:3 being
      the most frequently recovered, as it is worldwide. No clear seasonal pattern
      emerged although most isolations were made in the autumn-winter period. The age
      distribution showed two peaks, 0-4 (17.6%) and 25-29 year olds (13%). Infections
      in males outnumbered those in females (56:44). CONCLUSION: The results of this
      study show that Y enterocolitica is an important enteric pathogen in the Auckland
      region, particularly in children and young adults and it has identified a need
      for a case-control study to assess the relevant risk factors for acquisition of Y
      enterocolitica infections in New Zealand.

PMID- 7637925
TI  - Adolescent health--a descriptive study of a school doctor clinic.
AB  - AIM: To describe a school doctor clinic at a New Zealand secondary school.
      METHODS: A three phase study was designed and conducted at a coeducational
      secondary school in Auckland. Firstly, a health questionnaire was developed to
      assess adolescents' perceptions of their health status and use of primary health
      care services. The second phase was descriptive study of a newly established
      school doctor clinic. The doctor clinic was run twice weekly over a 3 month
      period in 1993. The third phase of the study was a clinic-based satisfaction
      survey. RESULTS: A 75% response rate was achieved, with a total of 221 health
      questionnaires completed from 292. Although the majority of students (n = 184,
      84%) considered themselves healthy, 16% (n = 36) described their health as only
      'fair' or 'poor'. Seventy one percent (n = 157) of students had seen their
      general practitioner in the preceeding twelve months. Thirteen percent (n = 142)
      of the school population consulted the school doctor clinic. Significantly more
      female, Maori and European students attended the school doctor clinic compared
      with the school demography. The commonest diagnoses for the doctor clinic were
      respiratory, skin and musculoskeletal problems. Thirty one percent of the
      diagnoses related to recognised adolescent health needs such as contraception,
      sexual health, nutrition, and psychosocial problems. Over two thirds of students
      at the first consultation had not seen another health provider. Students
      perceived that the doctor clinic overcame barriers such as access, cost and
      confidentiality. CONCLUSION: The school doctor clinic was well utilised, overcame
      some barriers to access and addressed many recognised adolescent health needs.

PMID- 7637926
TI  - Quinolones.

PMID- 7637927
TI  - Public Health Commission policy on bed sharing and SIDS.

PMID- 7637928
TI  - Bed sharing and cot death.

PMID- 7637929
TI  - Bed sharing and cot death.

PMID- 7637930
TI  - Laparoscopic assisted hysterectomy.

PMID- 7637931
TI  - The shaken infant syndrome.

PMID- 7637932
TI  - Community-acquired pneumonia due to Legionella feeleii serogroup 2.

PMID- 7637933
TI  - Diaphragmatic palsy and chiropractic manipulation.

PMID- 7637935
TI  - Air embolism from needle-less infusion ports.

PMID- 7637934
TI  - A lost pathological specimen.

PMID- 7637936
TI  - Prevalence of acne vulgaris in Auckland senior high school students.
AB  - AIM: To assess the prevalence and severity of acne vulgaris in adolescent
      students. METHOD: 867 students in Auckland sixth and seventh form classes were
      interviewed on the subject of acne vulgaris. Of these 847 students were examined
      and graded for severity of their acne using a modification of the Leeds technique
      which ranks severity according to number, extent and nature of the acne lesion.
      RESULTS: Ninety-one percent of males and 79% of females had some acne. Severe
      acne was present in 6.9% males and 1.1% females. Severe and moderately severe
      acne was significantly more common in males (OR = 2.6 95% Cl 1.73 < OR < 3.9). In
      the univariate analysis there was no association of moderately severe and severe
      acne with parental occupational group nor ethnicity. CONCLUSION: Moderate and
      severe acne is a common finding in Auckland senior high school classes with males
      being more affected than females.

PMID- 7637937
TI  - Stroke rehabilitation in south Auckland; the value of an effective rehabilitation
      unit.
AB  - AIM: To assess the validity of Barthel based poststroke triage, the effectiveness
      of a rehabilitation unit in minimising poststroke institutionalisation, and
      medical resource utilisation for stroke management. METHODS: A prospective study
      of stroke outcome for 115 consecutive patients admitted to Middlemore Hospital,
      Auckland, between March and September 1993, based on Barthel functional
      assessments at 1 week and 3 months poststroke, postdischarge domicile and
      duration of inpatient stay in both acute medical and rehabilitation units.
      RESULTS: For the 73 patients offered rehabilitation, 48 (76%) of the survivors
      were able to return home after a mean period of 6 weeks. Of 24 subjects with 1
      week Barthel scores of five or less, 15 of 19 (84%) survivors returned to their
      original domicile. Of eight patients with 1 week Barthel scores of two or less,
      all survived and five returned home. The median delay between admission by the
      acute medical service and transfer to the rehabilitation unit was only four days
      for the 70 patients involved. CONCLUSION: Our data provides local confirmation of
      internationally increasing acceptance of the effectiveness of rehabilitation
      units in reducing expensive long term institutionalisation and freeing up
      stressed acute medical resources.

PMID- 7637938
TI  - Improved detection of Chlamydia trachomatis in endocervical samples by using a
      new polymerase chain reaction assay.
AB  - AIM: To compare the performance of a commercially developed polymerase chain
      reaction (PCR) assay, Amplicor Chlamydia trachomatis from Roche Molecular
      Systems, with that of a standard enzyme immunoassay (EIA) system, Chlamydiazyme
      from Abbott Laboratories, which is currently used throughout New Zealand.
      METHODS: Cervical swabs were collected from 819 female patients attending the
      family planning clinic in Christchurch. These swabs were then analysed using the
      Amplicor and Chlamydiazyme assays. RESULTS: The prevalence of chlamydia infection
      was 4.2% by the Chlamydiazyme EIA method and 5.3% with the Amplicor PCR assay. In
      20 cases, where the results from the two assays were discordant, the conflict was
      'resolved' by using a third assay which detects a separate region of the
      chlamydia genome. This gave an overall prevalence of 5.8% of confirmed infections
      in this group. The Amplicor PCR assay detected 29.4% more cases than the usual
      EIA method. CONCLUSIONS: This study demonstrates that Amplicor PCR assay allows
      improved identification of C trachomatis infections in a population with a
      relatively low prevalence of infection. The Amplicor PCR assay detects a
      significant number of additional infections and should be considered for routine
      use. As the PCR assay is more expensive a shift in the price/payment structure
      may be required before this assay comes into widespread use. However, the reduced
      morbidity resulting from the detection and treatment of otherwise unrecognised
      cases should also be considered in any cost benefit analysis.

PMID- 7637939
TI  - Donor families experience of organ donation: a New Zealand study.
AB  - AIM: To investigate the experiences of New Zealand families who had given
      approval for organ donation. METHOD: A postal questionnaire was sent to all
      families in New Zealand over a 5 year period who had agreed to donate organs on
      the death of their family member. RESULTS: Of the 102 questionnaires sent, 49
      were returned completed. No respondents said it was the wrong decision in
      agreeing to donate organs. 31/49 respondents said that being asked caused no
      additional stress. 31/49 had previously discussed organ donation within their
      family. 16/49 knew the information on the donor's driving license. 38/49 said
      that they understood brain death at the time. 31/49 said the care, understanding
      and support given by the staff in the intensive care unit helped them most at the
      time. 23/49 would have liked further support from the transplant coordinators.
      32/49 would have liked written information at some stage. Even though they were
      not asked 25/49 volunteered that they would have liked information about
      recipient outcome. CONCLUSION: Our results reinforce and support the findings of
      previous research from New Zealand and other countries. These have been used to
      confirm and revise procedures in the planning of care for future donor families.

PMID- 7637940
TI  - Auckland Ambulance Service cardiac arrest data 1991-3.
AB  - AIM: To describe the results of three years of attempted resuscitation from
      prehospital cardiac arrest by the Auckland Ambulance Service. METHODS:
      Observational cohort study in a largely urban New Zealand population of 935,000.
      All cases of attempted resuscitation from out of hospital cardiac arrests
      occurring between 1 January 1991 and 31 December 1993. Main outcome measures were
      the number and outcome of patients receiving resuscitation from primary cardiac
      arrest. Core data conformed to Utstein recommendations. RESULTS: Of 1176 cases of
      consecutive cardiac arrest, 1069 (91%) were deemed primary cardiac arrest (978
      unmonitored and 91 monitored). Four hundred and sixty (43%) of the 1069 cases
      were transported to hospital. 240 (22%) were admitted and 135 (13%) were
      discharged. By initial rhythm, 693 (65%) of cases were in ventricular
      fibrillation (VF) and 96 (14%) were discharged. One hundred and forty three cases
      (13%) were in asystole, 113 (11%) were in electromechanical dissociation (EMD),
      29 (3%) were in an idioventricular rhythm. Of these 285 cases, only one survived
      to discharge (a 25 year old woman in EMD). There were 91 monitored arrests
      (cardiac arrest in front of ambulance officers). Fifty seven cases went into VF
      and 36 (63%) were discharged. Two cases in ventricular tachycardia became
      pulseless; each received a single DC shock and both were discharged. The
      remaining 32 cases of monitored arrest developed rhythms not amenable to DC
      shocks. None survived to hospital discharge. Eighteen (4%) of the 437 cases not
      receiving bystander cardiopulmonary resuscitation were discharged from hospital.
      Thirteen (7%) of the 197 cases receiving ineffective bystander CPR were
      discharged, and 64 (19%) of 330 cases receiving effective bystander CPR were
      discharged. CONCLUSION: Only those patients with prehospital cardiac arrest who
      were in ventricular fibrillation or ventricular tachyardia had a reasonable
      prospect of survival. Effective bystander CPR showed a substantial effect on
      patient survival to hospital discharge.

PMID- 7637941
TI  - Hyponatraemic hypertensive syndrome in association with bilateral renal artery
      stenosis.

PMID- 7637942
TI  - Helicopter retrievals, how sick are the patients?

PMID- 7637943
TI  - Screening for varicella in hospital staff.

PMID- 7637944
TI  - Bedsharing and smoking.

PMID- 7637945
TI  - Chronic fatigue syndrome.

PMID- 7637946
TI  - Regarding the safety of soy.

PMID- 7637947
TI  - Tuberculosis revisited.

PMID- 7637948
TI  - Focus on computer-generated eye problems.

PMID- 7637949
TI  - What you should know about barrier hand creams.

PMID- 7637950
TI  - Surgery for exocrine pancreatic cancer--who are the 5- and 10-year survivors?
AB  - 38 of 306 patients survived beyond 5 years after resection of an exocrine
      pancreatic carcinoma during a period from 1971 to 1993. Amongst the long-term
      survivors there were 12 patients with ductal, 22 with ampullary, 3 with distal
      bile duct and 1 with duodenal cancer. An active operative strategy was employed
      in order to resect the tumor whenever this was surgically possible. In a a
      retrospective analysis we have identified prognostic factors influencing long
      term survival. The long-term prognosis was largely dependent on the tumor entity.
      Ampullary carcinomas had a significant advantage in terms of long-term survival
      over all other tumor entities. Other prognostic factors associated with long term
      survival were curative tumor resection, absence of lymphatic and distant
      metastases and a low tumor malignancy.

PMID- 7637951
TI  - A biological study on the efficacy of low-dose subcutaneous interleukin-2 plus
      melatonin in the treatment of cancer-related thrombocytopenia.
AB  - The production of cytokines involved in platelet generation, including
      interleukin (IL)-3, IL-6 and IL-11, is stimulated by IL-2. However, the platelet
      number has been shown to decrease on IL-2 cancer therapy, and this side effect
      depends on the enhanced peripheral platelet destruction following the activation
      of the macrophage system by IL-2 itself. Our previous studies showed that IL-2
      induced macrophage activation may be counteracted by the pineal hormone melatonin
      (MLT). On this basis, a pilot study with IL-2 plus MLT was performed to evaluate
      its influence on the platelet number in cancer patients with persistent
      thrombocytopenia. The study included 20 advanced solid tumor patients, who
      received IL-2 at 3 million IU/day s.c. for 6 days/week for 4 weeks in association
      with MLT (40 mg/day orally). A normalization of the platelet number was achieved
      in 14/20 (70%) patients. This pilot study shows that the therapy with low-dose IL
      2 plus MLT, in addition to its previously described antitumor activity, may also
      be effective in the treatment of cancer-related thrombocytopenia.

PMID- 7637952
TI  - DNA ploidy pattern and cell cycle stage of tumor cells in soft-tissue sarcomas:
      clinical implications.
AB  - Staining and counting of argyrophilic nucleolar organizer region (AgNOR),
      segments of DNA with ribosomal genes, is useful for estimation of the
      proliferative activity in soft tissue sarcoma (STS). The precise role of AgNOR in
      STS, however, is still uncertain. In the present study, ploidy pattern and stage
      of cell cycle were analyzed in 151 cases of STS in the extremities and trunk, and
      their correlation with AgNOR and utility as independent prognostic factors were
      estimated. For this, microspectrophotometric and flow-cytometric analyses were
      done on paraffin-embedded material from 84 and 111 cases, respectively. Fifty
      five percent cases showed an aneuploid pattern with a less favorable prognosis.
      The range of the DNA index and percentage of cells in S + G2M phase were 0.89
      2.04 (mean +/- SD, 1.23 +/- 0.32) and 5.4-83.7% (mean +/- SD, 32.95 +/- 17.92),
      respectively. Tumors having less than 40% cells in the S + G2M phase showed a
      favorable prognosis compared to those over 40%. Both the ploidy pattern and stage
      of the cell cycle showed a good correlation with the AgNOR count: a high
      frequency of cases having aneuploidy and S + G2M phase in the AgNOR high count
      group. These findings provide a theoretical base for explaining the utility of
      AgNOR for the estimation of proliferative activity. In multivariate analysis,
      only AgNOR counts were a prognostic factor among histologic factors reflecting
      proliferative activity of tumors. The DNA ploidy pattern and the stage of the
      cell cycle was proved not to be an independent factor for prognosis.

PMID- 7637954
TI  - A multivariate analysis of prognostic factors including tumor response after
      endocrine therapy in advanced breast cancer patients.
AB  - Although clinicians want to know how tumor response affects the survival of
      advanced cancer patients, the direct comparison of response with survival is
      severely discouraged because of biases essentially involved. In 159 patients with
      advanced breast cancer treated with adreno-oophorectomy, we analyzed the survival
      of the patients using the Kaplan and Meier method with the landmark method
      (landmark time of 3 months after treatment). A multivariate analysis with the Cox
      proportional hazard model for survival with explanatory variables including
      response of patients at the landmark time (3 months after therapy) was performed
      in order to find probable prognostic factors. By the Kaplan and Meier curves with
      the landmark method, response category showed a significant difference in the
      survival of the patients (log rank test; p < 0.0001). In the Cox model in the
      patients of landmark time of 3 months after therapy, we found that response was
      the most powerful factor for survival out of 10 variables (p = 0.0001), and the
      dominant site of metastasis significantly and independently modified the survival
      length (p = 0.001). ER status was indifferent in the analysis; however, when the
      response category was not included, ER was shown to be most influential. We
      propose that a combination of the Cox model with the landmark method would be a
      rational and useful approach to estimate probable prognostic factors including
      treatment outcome variables such as response for the survival analysis in
      advanced cancer patients.

PMID- 7637953
TI  - Immunohistochemical detection of estrogen receptor in invasive human breast
      cancer: correlation with heat shock proteins, pS2 and oncogene products.
AB  - The authors immunohistochemically studied the expression of the estrogen receptor
      (ER), 27-kD heat shock protein (HSP27) and pS2 in 118 invasive primary human
      breast cancers. Positive nuclear staining of the ER was detected in 64% of the
      cases and was closely correlated with the biochemical assay (p < 0.0001). ER
      positive tumors were significantly decreased with tumor size and stage (p < 0.001
      each), but not with lymph node status. Positivity of the ER was correlated with
      the cytoplasmic expression of HSP27 (p < 0.005), pS2 (not significant) and HSP70
      (not significant). ER negativity was significantly correlated with the expression
      of p53, epidermal growth factor receptor (EGFR) and c-erbB-2 (p < 0.05 each).
      Thus, it was concluded that ER-positive breast carcinomas, relatively small in
      size, preferentially expressed HSP27, HSP70 and pS2 and that ER-negative tumors,
      relatively large in size, were predisposed to express p53, EGFR and c-erbB-2.

PMID- 7637955
TI  - Platelet activation and fibrinolysis in large bowel cancer.
AB  - Four coagulation indices [fibrinopeptide A (FpA), X degradation products (XDPs),
      platelet factor (PF4), beta-thromboglobulin (beta-TG)] were assessed in 38
      patients affected by large bowel cancer at different stages before surgery, 7 and
      30 days after it, to evaluate the capacity of such neoplasia to influence
      coagulation. The reported study showed that (1) FpA levels were elevated in
      nearly all cases both before and after surgery (thus it is a useful index for the
      diagnosis of such neoplasia, although its levels are not influenced by the
      presence of metastases), (2) increased levels of XDPs were found in a
      significantly (p < 0.05) higher percent of patients 7 days after surgery (no
      significant differences were observed in relation to the cancer stage), (3) PF4
      levels were in the normal range throughout the study, and (4) beta-TG levels were
      increased throughout the study in a high percentage of cases. It may be inferred
      that large bowel cancers may affect coagulation in either way(s), by triggering
      platelet activation and/or fibrinolysis. The most useful index for the diagnosis
      and follow-up of this neoplasia is FpA, although its levels are unaffected by the
      presence of metastases. The comprehensive evaluation of the four above-mentioned
      coagulation indices may give rise to the suspicion of large bowel cancer.

PMID- 7637956
TI  - Growth of human gastric carcinomas and expression of epidermal growth factor,
      transforming growth factor-alpha, epidermal growth factor receptor and p185c-erbB
      2.
AB  - We examined the expression of epidermal growth factor (EGF), transforming growth
      factor-alpha (TGF-alpha), epidermal growth factor receptor (EGFR) and p185c-erbB
      2 immunohistochemically and correlated the expression with growth in 66 cases of
      human gastric carcinoma. To evaluate growth, we used the bromodeoxyuridine (BrdU)
      labeling index in 51 cases and the radiographic growth rate in 15 cases.
      Expression of EGF was detected in 41 cases (62.1%), TGF-alpha in 42 cases
      (63.6%), EGFR in 34 cases (51.5%), and p185c-erbB-2 in 37 cases (56.1%). The BrdU
      labeling index ranged from 1.5 to 32.0%. The BrdU labeling index was higher in
      tumors that coexpressed EGF and EGFR or TGF-alpha and EGFR than in tumors without
      expression or in tumors that expressed growth factors or the receptors (p <
      0.01). The BrdU labeling index was also significantly higher in tumors with the
      expression of EGFR and/or p185c-erbB-2. Tumors with simultaneous expression of
      EGF, TGF-alpha, EGFR and p185c-erbB-2 had an association with a high BrdU
      labeling index. Moreover, all of these growth factors and receptors were
      expressed simultaneously in gastric carcinomas with rapid growth. These results
      suggest that the expressions of EGF, TGF-alpha, EGFR and p185c-erbB-2 are closely
      related and then play an important role in the growth of human gastric
      carcinomas.

PMID- 7637957
TI  - Elevated serum c-erbB-2 protein levels in patients with pancreatic cancer:
      correlation to metastasis and shorter survival.
AB  - Overexpression of the c-erbB-2 proto-oncogene has been shown to correlate with
      relapse and poor prognosis in adenocarcinomas of the breast and stomach. In
      pancreatic cancer, c-erbB-2 overexpression has been demonstrated using
      immunohistochemistry, but the relationship between serum c-erbB-2 level and
      clinical data has not been fully evaluated. In this study, serum c-erbB-2 protein
      levels were measured in 100 patients with pancreatic adenocarcinomas and in 9
      patients with mucin-producing tumors. Immunohistochemical studies for c-erbB-2
      protein were performed in 36 patients and 4.0 U/ml in healthy controls (p <
      0.001). The positive rate for serum c-erbB-2 was 34% (37/109) in patients with
      pancreatic cancer and 0% (0/66) in patients with gallstones and in healthy
      controls (p < 0.001). Immunohistochemical study disclosed that the positive
      staining rate was 28% (8/29) in common ductal adenocarcinoma specimens, 43% (3/7)
      in metastasis specimens, and 75% (3/4) in mucin-producing tumor specimens.
      Clinical evaluation revealed that 59% (22/37) of serum c-erbB-2-positive patients
      and 33% (24/72) of negative patients had liver or peritoneal metastases (p <
      0.01). The mean survival time was 154 days in the c-erbB-2-positive group and 220
      days in the negative group (p < 0.05). We suppose that c-erbB-2 is related to
      metastasis and progression of the disease in patients with advanced pancreatic
      cancer.

PMID- 7637958
TI  - HER-2 oncogene is not amplified in primary carcinoma of the fallopian tube.
      Austrian Cooperative Study Group for Fallopian Tube Carcinoma.
AB  - 73 women suffering from primary carcinoma of the fallopian tube underwent
      surgical excision of their tubes. The tissue was embedded in paraffin and
      investigated for HER-2 oncogene amplification with a quantitative polymerase
      chain reaction method. DNA could be extracted and successfully prepared in 65/73
      samples. None of the tissue samples exhibited amplified the HER-2 oncogene. Data
      suggest that the HER-2 oncogene does not play a role in tumor transformation and
      progression in fallopian tube carcinomas. This contrasts with observations in
      ovarian carcinomas, with which fallopian tube carcinomas share many clinical,
      histological and biochemical similarities.

PMID- 7637959
TI  - A comparison of two commercially available in vitro chemosensitivity assays.
AB  - In vitro chemosensitivity assays (IVCAs) are expensive laboratory tests utilized
      to assist oncologists in the selection of chemotherapeutic regimens. Their
      utility is disputed; yet, these assays continue to be requested because of the
      importance of the information they can provide and their scientifically logical
      approach. Therefore, we compared the results of two assays offered to clinicians
      at our hospital; the extreme drug resistance assay performed by Oncotech (OT) and
      the fluorescent cytoprint assays performed by Analytical Biosystems (AB). The two
      techniques used and the expression of assay results by the two companies are
      discussed. Twenty neoplasms, all at least 3 cm in diameter and predominantly of
      breast and ovarian origin, were compared. OT performed 74 drug assays on 17
      tumors, while AB performed 194 assays on the corresponding neoplasms; 3 neoplasms
      were insufficient for comparison. Evaluation of the results revealed apparent
      disagreement on at least 44 drug assays with complete disagreement on at least 2
      of the drugs tested in 12 of 17 cases. In conclusion, based on available
      information, comparisons between IVCAs show great variation in results;
      prospective studies are needed to evaluate commercially available assays for
      correlation with clinical outcome, and results should be expressed so comparisons
      can be readily made. Though utility may be limited to tumors resistant to
      standard therapy, cost and benefit to the patient will ultimately determine the
      fate of these tests.

PMID- 7637960
TI  - Effects of cycloheximide on chromatin-bound and -unbound PCNA in HeLa cells.
AB  - We examined the effects of cycloheximide on the amount of chromatin-bound and 
      unbound PCNA subpopulations in HeLa cells. The chromatin-bound PCNA content
      decreased rapidly in the presence of cycloheximide, whereas the reduction of the
      total amount of PCNA was minimal even 24 h after the treatment with
      cycloheximide. From these data, the half-life of PCNA was estimated to be 31.0 h
      for chromatin-bound PCNA and 276.8 h for the total.

PMID- 7637961
TI  - Recombinant human erythropoietin treatment in elderly cancer patients with
      cisplatin-associated anemia.
AB  - The efficacy of recombinant human erythropoietin (rHuEPO) on the increase in
      hemoglobin levels was assessed in patients with cisplatin (CDDP)-induced anemia
      older than 70 years. Furthermore, we compared the results obtained in this group
      of patients with those observed in other patients receiving rHuEPO for a CDDP
      associated anemia with similar clinical features (chemotherapeutic regimen,
      primary tumor; CDDP cumulative dose) but of an age less than 70 years. Twenty
      patients older than 70 years with a CDDP-associated anemia (hemoglobin levels <
      90 milligrams) received rHuEPO at the dose of 100 U/kg subcutaneously, three
      times a week. The control group consisted of 20 younger patients, anemic after
      CDDP chemotherapy, treated with rHuEPO. All patients were evaluable for response
      and toxicity. Hemoglobin concentrations showed a statistically significant
      increase after the 3rd, 6th and 9th week of therapy in both older (93.1 +/- 10.7,
      103.5 +/- 8.2 and 102.7 +/- 8.2, respectively, vs. baseline, 84.6 +/- 4.9) and
      younger patients (95.3 +/- 11.7, 101.5 +/- 13.4 and 101.9 +/- 8.7, respectively,
      vs. baseline, 86.6 +/- 4.0). Furthermore, 30% of older patients required blood
      transfusions versus 35% of younger patients, with the mean unit of blood
      transfused per patient being 0.7 U in elderly and 0.65 U in younger patients.
      Treatment was well tolerated with no significant side effects. The CDDP-induced
      anemia seems to be corrected by rHuEPO also in elderly patients, without
      differences with respect to younger patients.

PMID- 7637963
TI  - [Diagnostic value of abdominal ultrasonography and endoscopic retrograde
      cholangiopancreatography in obstructive jaundice].
AB  - The diagnostic value of ultrasonography (US) and endoscopic retrograde cholangio
      pancreatography (ERCP) was compared, in 66 patients with bile duct obstruction,
      who underwent subsequent biliary surgery. The level of the blockage was diagnosed
      by US with a 80%, by ERCP with a 95.4% sensitivity, while the cause of the
      obstruction was determined with a 50% and a 89% sensitivity, respectively.
      Predictive value of these examinations is over 90%. Based on the clinical results
      and on the high diagnostic value of the above mentioned examinations, it is
      essential to fill up the bile ducts with direct contrast material.

PMID- 7637962
TI  - Antiemetic efficacy of tropisetron in patients failing previous antiemetic
      therapy.
AB  - Tropisetron was studied for efficacy and safety in 164 patients who were
      refractory to other antiemetic agents. 5 mg tropisetron was given intravenously,
      followed by 5 mg by mouth per day for 4 days. Complete prevention of nausea and
      vomiting was documented in 42% of patients on day 1 of cycle 1. Delayed nausea
      and vomiting were prevented in 41% in the first cycle. The antiemetic control did
      not decrease with subsequent cycles. Side effects ascribed to tropisetron were
      mild.

PMID- 7637964
TI  - [Experience with echocardiographic examination of patients with left bundle
      branch block under intensive care].
AB  - In the 3 and a half year patient material of their Intensive Care Unit the
      authors studied the diagnostic value of the echocardiography in left bundle
      branch block. From the 925 patients treated this period they analysed
      retrospectively the clinical data of 51 patients with left bundle branch block.
      In 37 cases acute myocardial infarction was suspected (group A), 14 patients were
      hospitalized because of severe left ventricular dysfunction without chest pain
      (group B). The echocardiography was performed always within 48 hours after
      admission. In 18/37 respectively 8/14 cases the left bundle branch block had
      already been known from the previous examinations. In the group A the enzyme test
      verified acute myocardial infarction in 23 patients, in each of them segmental
      wall motion abnormality--either akinesis or dyskinesis--was detected by
      echocardiography. In group B 5 dilated cardiac diseases, 1 aortic and 2 mitral
      vitiums were verified by echocardiography. From the 6 patients of the group B the
      wall motion abnormalities were caused by acute myocardial infarction in 1 patient
      and by a previous myocardial infarction in 5 patients. At the Intensive Care Unit
      8, and during the further observation in hospital 5 patients died. In each cases
      the section reinforced the findings of the echocardiography. According to the
      authors' experiences, echocardiography is proved to be a very useful help in the
      acute cardiac care of patients with left bundle branch block.

PMID- 7637965
TI  - [Early diagnostic pitfalls in esophageal perforation and spontaneous rupture of
      the esophagus].
AB  - In this retrospective study (1981-1993) of 31 cases of esophageal perforations
      and ruptures circumstances the delay or misdiagnosis with undoubtable influence
      on the survival have been discussed. The over-all mortality was 16.1% but in
      cases of early (24 h) perforations or ruptures (12) no patients were lost. The
      unfavourable consequence of the superficial case history, underestimated pain,
      incomplete roentgenographic study, diagnostic confusion inadequate surgical
      exploration and misinterpreted postoperative complications of the formal
      esophageal surgery are analyzed. The authors emphasized the methods to decrease
      the number of the false-negative contrast esophagograms as well as the value of
      the intraoperative endoluminal diluted methylin-blue injection to detect
      esophageal leak. The early diagnosis is the first prerequisite for a favourable
      outcome in this life-threatening emergency.

PMID- 7637966
TI  - [Botulism in infancy].
AB  - According to international references the publication ascertains the etiologic
      role of neurotoxin producing Clostridial spp., other than C. botulinum in Infant
      botulism. Authors report on the first Hungarian case of Infant botulism. The
      organism isolated -- C. barati -- is responsible only for a small proportion of
      published cases. Authors point out the conjunction of Infantile botulism and crib
      death.

PMID- 7637967
TI  - [Role of endogenous basic fibroblast growth factor in experimental duodenal
      ulcer].
AB  - Authors investigated the role of endogenous bFGF in the development of
      experimental duodenal ulcer induced by cysteamine. The changes in endogenous bFGF
      in duodenum were examined by immunohistochemical method in the early stages of
      ulceration. A significant decrease was found in the immunoreactivity of bFGF in
      rat duodenal mucosa 12 and 24 hr after the administration of the duodenal
      ulcerogen cysteamine. Thus, in addition to being a novel potent pharmacologic
      agent, bFGF may play a pathophysiologic role in ulcer pathogenesis and healing.

PMID- 7637968
TI  - [Ignac Langer (1819-1895), forgotten pioneer of American-Hungarian medical
      connections].

PMID- 7637969
TI  - [From the history of the Institute for Health Examination (Student Health) at the
      Semmelweis Medical University].

PMID- 7637970
TI  - [15-year echocardiographic follow-up of acromegalic patients].
AB  - An echocardiographic follow-up of 25 patients (pts) was performed, after the
      first examinations in 1978-1979. 15 pts have died in the last 15 years (Group 1),
      while 10 still living (Group 2). In Group 1 either the impaired global left
      ventricular at the time of the first echocardiography predicted a high mortality
      i.e. there were only two pts with normal echocardiographic findings. The other 6
      acromegalic pts with a "normal heart" have survived. The left ventricular
      hypertrophy of pts in Group 2 was observed to increase during the 15-year follow
      up, because of the development of systemic hypertension. In conclusion, the
      echocardiographic findings are of a good predictive value in estimations of the
      survival rate in acromegalic pts.

PMID- 7637971
TI  - [Ultrasound guided fine-needle aspiration biopsy in the diagnosis of
      hepatocellular carcinoma].
AB  - This retrospective study was undertaken to evaluate the diagnostic usefulness of
      244 sonographically guided fine- needle aspiration biopsy in 226 patients with
      ultrasonographically suspected hepatic malignant lesions. A final diagnosis of
      malignancy was established in 166 cases (73%) (145 hepatocellular carcinoma, 21
      metastasis); benign lesions were aspirated in 60 cases (27%). The diagnostic
      sensitivity of this technique was 93%, with 100% specificity. When both cytology
      and microhistology were obtained, the positive correlation of the two techniques
      was 80% In the series of 244 fine-needle aspiration biopsy the authors had only
      one acute complication. They report one case of needle tract tumor seeding after
      biopsy. These results confirm the usefulness of sonographically guided fine
      needle aspiration biopsy in diagnosing malignant hepatic tumors. The procedure is
      simple, safe, free of important side effects. The authors believe that ultrasound
      guided fine-needle aspiration biopsy represents the first choice of invasive
      technique in the assessment of hepatic focal benign lesions and malignant
      tumours.

PMID- 7637972
TI  - [Morphological differences in carotid angiograms and their relation to age].
AB  - The level of carotid bifurcation, frequency of the kinking of the internal
      carotid artery, correlation between the diameter of carotid arteries and the age
      of the Hungarians was examined. The cervical level of carotid bifurcation,
      diameter of extracranial carotid arteries, frequency of kinking of internal
      carotid arteries were measured on conventional carotid angiograms in 490
      Hungarian patients (517 arteries, age range 12-77 yr). The cervical level of the
      carotid bifurcation was determined by comparison with cervical vertebra. The most
      frequent level of carotid bifurcation was found at the middle part of 4th
      cervical vertebra. The position shifted higher with ageing. The mean common
      carotid artery diameter was 9.24 +/- 1.58 mm in males and 7.80 +/- 1.10 mm in
      females. The mean internal carotid artery diameter was 8.56 +/- 1.84 in males and
      7.66 +/- 1.39 in females. The mean external carotid artery diameter was 5.53 +/-
      1.11 mm in males and 4.76 +/- 0.91 in females. The diameter of the common carotid
      artery has a significantly positive correlation with age (p < 0.05) but internal
      carotid artery and external carotid artery had no similar correlation. The
      kinking of internal carotid artery was observed frequently in patients who had
      higher level of carotid bifurcation.

PMID- 7637973
TI  - [Experience with long term low dose methotrexate treatment in rheumatoid
      arthritis and arthritic psoriasis].
AB  - The clinical efficacy and the side effects of a long term (max. 42 months, min. 5
      months) weekly pulse methotrexate treatment (10 mg/week) were investigated in 31
      rheumatoid arthritis patients and in 14 with psoriatic arthritis. A reduction in
      the number of inflamed joints and diminished duration of morning stiffness could
      be observed together with a decrease of pain and of the erythrocyte sedimentation
      rate in rheumatoid arthritis. In patients with psoriatic arthritis the intensity
      of joint pain was not influenced considerable and the decrease of the erythrocyte
      sedimentation rate was not as great as in rheumatoid arthritis patients.
      Ineffectivity of the methotrexate treatment occurred in one rheumatoid arthritic
      patient. The methotrexate treatment could not be carried on in two rheumatoid
      arthritic patients because of adverse side effects.

PMID- 7637974
TI  - [Plica polonica].
AB  - The author summarizes the essentials and history of the plica polonica disease
      and describes some of his own experiences in diagnosis and treatment. It is
      remarkable, that the monographs of the internal medicine and the hungarian
      monographs of dermatology, with the exception of two, didn't even mention this
      phenomenon in this century. Besides, no original publications can be found in the
      hungarian medical literature about this topic. However we can find people with
      this syndrome in Hungary also at the present time. It can be connected with the
      increasing ageing and growing poverty in our country.

PMID- 7637975
TI  - [Primary endoscopy of the stomach].

PMID- 7637976
TI  - [The measles vaccine is not teratogenic!].

PMID- 7637977
TI  - [Screening of newborn infants for medium-chain acyl-CoA dehydrogenase deficiency
      in Hungary].
AB  - The authors publish for the first time the Hungarian frequency of the medium
      chain acyl-CoA dehydrogenase (MCAD) deficiency. The determination was carried out
      with molecular biological methods in 1121 newborns. The disease is inherited as
      an autosomal recessive trait, caused by mutation in the enzyme gene. The
      deficiency is extremely frequent in the Anglo-Saxon populations. Here it is as
      common as phenylketonuria. The first episode presents usually in the first 2
      years of life, and the mortality may approach 60 percent. Early and prompt
      diagnosis can lead to an effective management of the disorder. The severity of
      the disease and its frequency in foreign countries made the screening necessary.

PMID- 7637978
TI  - [Motion of the mitral anulus and suitability of the motion amplitude for
      determination of left ventricular function in Q-type myocardial infarct].
AB  - Cardiac apex hardly changes its location during the time of cardiac cycle, but
      the mitral anulus--representing cardiac base--has a systolic descent toward the
      apex and in diastole moves to the left atrium. The whole amplitude of mitral
      anulus motion is so useful indicator of left ventricular systolic function as
      ejection fraction derived from enddiastolic and endsystolic parameters. Mitral
      anulus motion amplitude easy to measure noninvasively by echocardiography.
      Authors examined 110 patients with their first, Q-type acute myocardial
      infarction 7-10 days after the onset of symptoms. In the same time ejection
      fraction value was assessed by radionuclide ventriculography. Data of ejection
      fraction and mitral anulus motion amplitude were compared. Their conclusions: 1.
      mitral anulus motion amplitude well correlated with left ventricular ejection
      fraction 2. patients had a decreased mitral anulus motion amplitude at the site
      of infarction 3. investigation of mitral anulus motion amplitude is an useful and
      easy to make method to assess of systolic function of left ventricle in acute
      myocardial infarction.

PMID- 7637979
TI  - [The place of micro- and modern mini-laparotomy in the management of biliary
      calculi].
AB  - The authors treated 537 patients biliary stone disease between 1-st january 1991.
      and 1-st june 1994. With the conventional method of 20 cm of the subcostal
      incision, they operated 250 patients, among them 17 (6.8%) also had the common
      bile duct stone. There was no case of mortality and common bile duct injury. The
      postoperative morbidity was 12.8%. The average days of treatment was 9. With
      micro- and modern mini-laparotomy 287 cases were operated, 16 (5.5%) of them had
      common bile duct stones which were extracted during the process of
      cholecystectomy. In one case transduodenal sphincterectomy was performed. There
      was no case of mortality and injury of common bile duct. The postoperative
      morbidity was 10.4%. There was 6 cases of conversion (2.09%). The average period
      of treatment was 5 days. The treatment of biliary stone disease by micro- or
      modern minilaparotomy does not cause more danger to the patients than the
      conventional subcostal method. This approach is suitable for the surgical
      treatment of all kinds of biliary stone disease. This method is also suitable to
      extract a stone (stones) from the common bile duct discovered during
      cholecystectomy. This method has a pleasant cosmetical results.

PMID- 7637980
TI  - [Familial hyperinsulinism].
AB  - The authors present the case history of a 2 year old child suffering from
      nesidioblastosis. Severe non-ketotic symptomatic hypoglycaemia developed within
      the first hour of birth. Diagnosis of nesidioblastosis was confirmed by high
      insulin concentration accompanying hypoglycaemia, the increase in blood glucose
      level after glucagon administration and the stabilization of blood glucose level
      by continuous high rate glucose infusion. Normal blood glucose concentration was
      achieved by combined medical treatment (diazoxide, chlorothiazide and
      prednisolone) and the administration of starch. The authors present by familial
      form of the disease with autosomal recessive inheritance pattern and stress the
      significance of the intrauterine diagnosis. They summarize the main diagnostic
      and therapeutical management of the disease with special emphasize of the early
      intervention in order to prevent severe brain damage.

PMID- 7637981
TI  - [Pathological features of Bela Bartok as reflected in his family tree].

PMID- 7637982
TI  - [Philip Hench, cortisone and the Mayo Clinic].

PMID- 7637983
TI  - [Once more about the Index of Hungarian Medical Writing].

PMID- 7637984
TI  - [Intravenous glycerin infusion and intravascular hemolysis].

PMID- 7637985
TI  - [Data on the clinical pathology of vascular dementia].
AB  - The exact diagnosis of dementias proved to be very important in the increasing
      research activity of Alzheimer's dementia. The National Stroke Programme stresses
      the significance of the study of the other--relatively frequent--form of dementia
      i.e. the much more intensive research of the vascular dementia. This study
      involved 287 clinical and pathological cases of vascular dementias. The 195
      clinical cases agreed with the probable and possible criteria of vascular
      dementia. The pathological examinations of 92 cases proved the definite category
      of diagnosis. Four groups of vascular dementias should be differentiated among
      the pathologically verified as well as in the clinically selected cases which
      were considered of practical--prognostic and therapeutic importance. The
      Hachinski's ischemic scale appeared to be reliable approximately in 90 percent in
      the differential diagnosis between the vascular and Alzheimer dementias
      especially in the multi-infarct group. The urgent diagnosis and adequate
      admission of the demented patients should be the task of the house physicians
      beside the therapeutical recommendations, mental training and the rehabilitative
      activity emphasized in the report. Furthermore the postgraduate education of
      house physician considering the dementias as well as the popular publications on
      dementias for the patient's relatives should also be necessary associated with
      good organization and with financial support.

PMID- 7637986
TI  - [Management of hypertensive dyskinesia of Oddi's sphincter. Correlation between
      the frequency of complications from endoscopic sphincterotomy and the diameter of
      the common bile duct].
AB  - OBJECTIVES: to evaluate the treatment possibilities in different forms of
      sphincter of Oddi dysfunction (SOD), in particularly that of the hypertonic
      sphincter of Oddi dyskinesia (HOD, biliary type group III). In the first part of
      retrospective evaluation the higher complication rate of endoscopic
      sphincterotomy (EST) and its probable causes were analysed. MATERIAL AND METHODS:
      The frequency and reasons of post-EST complications were retrospectively
      evaluated in a three-year (1990-1992) EST material of two gastroenterological
      departments using identical treatment principles and methods. Endoscopic
      sphincterotomies performed for bile duct stone extraction or treatment of HOD in
      cholecystectomized patients were included only. The data of 308 patients were
      analysed regarding two areas: 1. EST was performed for HOD treatment in 20
      patients, and in 288 patients for stone removal, 2. the diameter of common bile
      duct was found non-dilated in 40 patients, and dilated in 268 patients,
      respectively. RESULTS: 1. The frequency of complications in the group of patients
      with EST for HOD treatment was significantly higher: 8/20 (40%) vs. 17/288 (5.9%)
      (p < 0.01). 2. There was also a significant difference in the percentage of total
      complications between the patients of nondilated bile ducts and those patients
      with dilated bile ducts: 8/268 (3.3%) vs. 17/40 (42.50%) (p < 0.01), detailed:
      bleeding: 4/268 vs. 6/40, pancreatitis: 4/268 vs. 10/40, and perforation: 0 vs.
      1/40. CONCLUSIONS: Therapeutic endoscopic sphincterotomy is more hazardous in
      patients with non-dilated bile ducts, thus evidently also in patients suffering
      from the biliary III. type (hypertonic Oddi-sphincter dyskinesia) of sphincter of
      Oddi dysfunctions.

PMID- 7637988
TI  - [Epidemiology of psychosomatic symptoms and its effect on the self-evaluation of
      general health in university students].
AB  - This paper reports on the prevalence of some common psychosomatic symptoms as a
      part of a larger study of health state and health risk behaviour of a medical
      student population in Szeged. The prevalence of psychosomatic symptoms was
      considered as a health-related variable. In the study 691 students participated,
      the investigation was carried out by survey method, using self-completed
      questionnaire. In both sexes, backache and sleeping disorders were the most
      frequent symptoms. Furthermore, men reported stomach ache and palpitation in
      higher occurrence, while in women stress-related headache and chronic fatigue
      were the most common among the self-reported symptoms. The index of symptoms were
      significantly higher among women than men (p < 0.0001). Prevalence of
      psychosomatic symptoms proved an important variable affecting self-perceived
      health. The literature reviewed by the authors suggests that health state of
      medical students are significantly better than students of other colleges.
      Unfortunately, the morbidity and mortality data of physicians show inverse
      results among other intellectual populations. The authors suggestion is applying
      standardised method and cooperation among epidemiological teams working on this
      question.

PMID- 7637987
TI  - [Hemo-rheologic and antioxidant changes in acute human pancreatitis].
AB  - In earlier studies of authors on acute and intermittent human pancreatitis it
      appeared that oxygen radicals may have important role in inflammations of
      pancreas. Therefore, detailed and systematic studies have been started in order
      to understand the rheological characteristics of human red blood cells (RBCs),
      antioxidant enzymes and other antioxidant parameters in clinically serious acute
      pancreatitis. Measurements of antioxidant system of blood, plasma and
      haemolysates have indicated prooxidant preponderance, and have apparently well
      reflected the "oxidative stress" conditions of the organism.

PMID- 7637990
TI  - [Remembering Emil Gyurman, M.D].

PMID- 7637989
TI  - [Imported schistosomiasis with late complications].
AB  - Schistosomiasis is a worm disease which causes a high mortality rate all over the
      world. The life span of worms can be 20-30 years, so if the acute phase of the
      disease is not fatal very often late complications can happen. Here we
      demonstrate two patients who suffered from different late complications of
      Schistosomiasis imported to our country. These two cases show the difficulty of
      diagnosis and therapy of such illnesses.

PMID- 7637991
TI  - 99th Annual meeting of the American Academy of Otolaryngology Head and Neck
      Surgery Foundation, Inc. New Orleans, Louisiana, September 17-20, 1995.
      Abstracts.

PMID- 7637992
TI  - [In memory of Ivo de Carneri (1927-1993)].

PMID- 7637994
TI  - [Sandflies in Italy: observations on their distribution and methods for control].
AB  - The paper analyzes published and unpublished data of sandfly collections carried
      out in Italy by one of the authors (M.M.) over a period of 18 years (1975-1993).
      These data are discussed in relation to the collection methods and the habitats.
      The leishmaniasis foci surveyed are localized in 11 regions of Central and
      Southern Italy and in the two main islands, Sicily and Sardinia. Five collection
      methods were used: i) sticky traps, ii) light traps, iii) window exit traps, iv)
      emergence traps, and v) hand catches. Captures were performed in domestic and
      sylvatic habitats in rural, urban and periurban areas. A total of 81,915
      sandflies has been collected. Specimens were identified as belonging to 6
      species: Phlebotomus perniciosus (46.1%), P. perfiliewi (43.8%), P. major (0.2%),
      P. mascittii (0.1%), P. papatasi (0.3%), and Sergentomyia minuta (9.5%). P.
      perniciosus, P. perfiliewi and S. minuta have been reported in almost all the
      regions samples, P. major only in 3 regions of South Italy (Apulia, Calabria and
      Sicily), P. mascitti in 4 regions of Central Italy (Tuscany, Latium, Abruzzo,
      Molise) and in Campania, P. papatasi in 6 regions without any definite
      geographical distribution. From the analysis of sticky trap captures P.
      perniciosus seems to be the prevalent species in the domestic habitat (65.6%)
      even if present in the sylvatic one (21.8%). The report of P. perniciosus in both
      situations might indicate the ability of the species to colonize a large range of
      habitats. P. perfiliewi resulted as the predominant species (88.1%) in the
      domestic area from collections with CDC light traps. S. minuta was the most
      abundant species in the sylvatic conditions (76.6%) while P. papatasi showed a
      clear endophilic behaviour reaching high percentages only in bedrooms and
      stables. Moreover, taxonomic characters of spermathecae utilized in species
      identification are reported.

PMID- 7637993
TI  - [Echinococcosis/hydatidosis in children: combined medical and surgical
      treatment].
AB  - The outcome of 5 children with visceral hydatid cysts treated with Albendazole
      and surgical therapy is reviewed. The diagnoses were confirmed by immunological
      tests, X-ray, ultrasound scanner (US) and computer tomography. The therapeutic
      approach was correlated to the type of infection pictures. Immunological tests, X
      ray and US were performed with the aim to evaluate the response to the
      therapeutic protocol. Combination of pharmacological and surgical treatment
      resulted in a complete resolution for all patients without any recurrence and
      further dissemination of infection.

PMID- 7637995
TI  - [Furuncular myiasis caused by Cordylobia anthropophaga: description of a case
      from Tanzania].
AB  - We report a case of a tourist, coming back from Tanzania, who presented with a
      foruncle on the left thigh diagnosed as a bacterial infection, which eventually
      turned out to be a myiasis foruncle. The patient said he had sat on the ground in
      short trousers. The lesion was covered with petroleum jelly and the larva was
      observed migrating from the lesion and subsequently extracted with forceps. The
      morphology of larval spiracles allowed to characterize the species as Cordylobia
      anthropophaga. Behaviour of the most common myiasis-producing flies, their life
      cycle and the way of infection are briefly described. Foruncular myiasis is a
      typical example of a tropical disease that can be misdiagnosed by clinicians in
      Western Countries where this pathology is uncommon.

PMID- 7637996
TI  - Acaricidal agents of natural origin against Psoroptes cuniculi.
AB  - Lavandula angustifolia Miller essential oil and some of its main constituents,
      i.e. linalool, linalyl acetate, and camphor were tested in vitro for their
      bioactivities against Psoroptes cuniculi (Delafond, 1859), mite of the rabbit.
      The essential oil and linalool were found to have very powerful miticidal
      activities.

PMID- 7637997
TI  - [Parasitic horse ticks in Italy. Observations on their distribution and
      pathogenic role].
AB  - The following 13 species of ticks, belonging to Ixodidae family, were recorded in
      Italy on horse (Equus caballus) since 1931: Ixodes ricinus, I. gibbosus,
      Haemaphysalis inermis, H. parva, H. punctata, H. sulcata, Dermacentor marginatus,
      Rhipicephalus sanguineus, Rh. bursa, Rh. turanicus, Hyalomma marginatum, Hy.
      detritum, Boophilus annulatus. The regional distribution and the role of the
      species in the transmission of pathogens are reported.

PMID- 7637998
TI  - Estimation of the time required by the malaria parasites to cross the digestive
      tract to reach blood in mice inoculated by the oral route.
AB  - In a previous report we described the transmission of the malaria parasites by
      the oral route in a murine model. Later, we performed some experiments to
      demonstrate the transmission of malaria infection by cannibalism. Now we commence
      to look for the site, mechanism and stages of the parasite involved in crossing
      the alimentary canal to reach blood and start the infection. To know the invasive
      stage of the parasite and the way it penetrates, we wanted first to find the
      level of the digestive tract through which the parasites cross, to restrict the
      area to be studied. We proposed that the crossing place would be known, if the
      crossing time of the parasite could be established. Mice were orally inoculated
      with Plasmodium yoelii yoelii infected blood and their blood was transferred at
      different times into clean recipient mice intraperitoneally. Malaria infection
      detected in recipient mice proved that infective forms of the parasite were
      circulating in the donor mice at the time the blood samples were taken. In this
      way, we observed that: i) although most parasites required between 2 to 10 min
      for crossing the alimentary canal, in some case the process can last for 22 hrs;
      ii) the parasites circulate in blood for variable periods of time (only two
      minutes in the shortest, and from 10 min on in the longest) being infective to
      blood recipients. Most orally-inoculated mice whose blood infects other mice,
      became transient carriers of parasites unable to establish in them.

PMID- 7638000
TI  - [Temporal distribution of ticks (Acarina: Ixodidae) in "Macchia Grande" park in
      Manziana in the province of Rome].
AB  - Temporal distribution of tick species was studied in the woodland "Macchia
      Grande" of Manziana in the province of Rome, Italy. A total of 2,494 ticks was
      collected by means of drag sampling during one year of survey (1993). Among the
      species identified, Ixodes ricinus (Linnaeus, 1758) (95.9%) was the most
      abundant, followed by Haemaphysalis inermis (Birula, 1895) (2.2%), Rhipicephalus
      bursa (Canestrini e Fanzago, 1877) (1.8%), Dermacentor marginatus Sulzer, 1776)
      (0.1%). I. ricinus was present during the whole year, showing a diphasic trend,
      with peaks in January-April (95-173 specimens per drag) and in November-December
      (29-126); H. inermis was recovered only during the cold season (January-April and
      in December) with the highest density in February (7); Rh. bursa was collected
      from May to October showing maximum occurrence in July (10). The presence of I.
      ricinus and H. inermis, proven vectors of Borrelia burgdorferi (Lyme disease) and
      TBE virus, is discussed in relation to the possible exposure risk for park
      visitors and operators.

PMID- 7637999
TI  - Sensitivity to antimalarial drugs by Plasmodium falciparum in Goundry, Oubritenga
      province, Burkina Faso.
AB  - Plasmodium falciparum susceptibility to chloroquine in vivo and to chloroquine,
      mefloquine, quinine, amodiaquine and sulfadoxine/pyrimethamine in vitro was
      investigated in children living in Goundry village, Oubritenga Province (Burkina
      Faso) in November 1992. An extended WHO in vivo field test was used, with follow
      up on days 2, 4, 7, 14, 21 and 28 after treatment with 25 mg chloroquine per kg
      body weight given over 3 days, in children from 2 to 8 years old with P.
      falciparum monospecific infection, asexual parasitaemia > 800
      parasites/microliter of blood and negative Bergqvist urine tests. At the same
      time, the in vitro response was assessed using WHO standard test kits. Out of the
      71 in vivo responses examined, 50 (70.4%) were classified as resistant to
      chloroquine at RI (43.6%) or RII (26.8%) levels. There were no RIII responses.
      Out of the 43 isolates tested for chloroquine susceptibility in vitro, 32 (74.4%)
      were resistant to the drug with mean EC50 and EC99 values of 1.41 mumol and 10.96
      mumol/l of blood, respectively. Resistance to sulfadoxine/pyrimethamine in vitro
      was observed in one out of 19 tested cases, with mean EC50 and EC99 values of
      0.00002 mumol and 35.05 mumol/l of blood, respectively. All isolates were
      inhibited by mefloquine at 12.8 mumol/l of blood, quinine at 51.2 mumol/l of
      blood and amodiaquine at 0.4 mumol/l of blood, indicating full sensitivity to
      these 3 drugs. The present study demonstrates the high prevalence of chloroquine
      resistant strains of P. falciparum in the study area of Burkina Faso and
      indicates that isolates resistant to sulfadoxine/pyrimethamine may also be
      present.

PMID- 7638001
TI  - [Aedes albopictus (Skuse) (Diptera, Culicidae) in eastern Veneto].
AB  - A survey was carried out in autumn 1992 and spring-autumn 1993 to study the
      seasonal distribution and the dispersal of Aedes albopictus (Skuse) in
      Portogruaro (province of Venice; North-Eastern Italy). Larvae and pupae were
      found from May through September; the larvae hatching from eggs after the end of
      September seemed unable to complete development. The adults bit until October.
      The mosquito spread in new areas of Portogruaro town, even after insecticidal
      treatments. Private areas seemed to play an important role in the preservation of
      the infestation, as they were not treated by the public pest control service.

PMID- 7638003
TI  - [Re-description of Syncyamus aequus, Lincoln and Hurley, 1981 (Amphipoda:
      Cyamidae), and ectoparasite of Stenella coeruleoalba (Meyen, 1883) and first
      discovery in Italian waters].
AB  - Syncyamus aequus Lincoln & Hurley, 1981, an amphipod parasite reported for the
      first time in South African waters, is re-examined in order to clarify the
      taxonomic value of some morphological characters not described in detail in the
      original description and in the following records (Raga, 1988; Sedlak-Weinstein,
      1991). Three females (two ovigerous) and six males were collected from two
      specimens of Stenella coeruleoalba (Meyen, 1833) stranded along the Central
      Thyrrenian coasts in 1988 and 1993. The amphipods fixed and stored in 70 degrees
      ethanol were cleared with lactophenol for examination. Drawings were made with
      the aid of a Leitz microscope drawing attachment. The specimens examined showed
      the presence of spines located on pereopods I and II, which were lacking in the
      original description of S. aequus. The authors had the opportunity to compare the
      specimens (male, female and ovigerous female) with the paratype (PEMK2g)
      deposited in the Natural History Museum of London. The present re-examination
      reveals a morphological homogeneity among the specimens collected in Italian
      waters, the paratype and the individuals recorded by Raga (1988), thus suggesting
      that they belong to the same species, having a broad geographical distribution.
      This is the first record of S. aequus in Italian waters.

PMID- 7638002
TI  - Experimental Trypanosoma congolense infection on naturally occurring ticks in
      N'dama and Gobra zebu cattle.
AB  - The effects of experimental Trypanosoma congolense infection in Gambian N'dama
      and Gobra zebu cattle on number of naturally-occurring adult ticks attaching were
      studied. An indirect fluorescent antibody test was performed to detect
      serological prevalence of Cowdria ruminantium antibody. The intravenously imposed
      trypanosome infection did not result in significant (P > 0.05) differences in
      Amblyomma variegatum and Hyalomma spp. infestations between control and infected
      N'dama cattle. Control N'damas carried significantly (P < 0.001) lower numbers of
      A. variegatum and Hyalomma spp. than the control zebus. Serological frequency of
      C. ruminantium antibody was similar in both control or infected N'dama and in
      control or infected zebu cattle. No deaths occurred among N'dama cattle, while
      all six trypanosome infected zebus progressively died within nine weeks post
      infection but trypanosomosis was excluded as the primary cause of death. Examined
      Giemsa-stained blood smears were negative for the presence of tick-borne micro
      organisms. Four positive cases of cowdriosis were identified during post-mortem
      examination. It was concluded that N'damas, even when submitted to trypanosome
      infection, react consistently better than Gobra zebus to tick attachment. These
      results emphasize the benefits of rearing disease resistant cattle breeds, such
      as N'dama, in areas where risks of trypanosomosis and cowdriosis coexist.

PMID- 7638005
TI  - Visceral larva migrans in mice experimentally infected with Baylisascaris
      transfuga (Ascarididae: Nematoda).
AB  - Laboratory bred albino mice, weighing 20 to 25 g, were orally infected with 2000
      Baylisascaris transfuga infective eggs each. Mice were randomly chosen and
      sacrificed on days 1, 2, 3, 10, 15, 24 and 70 post-infection. Samples of
      intestine, mesenteric lymph nodes, liver, lungs, heart, spleen, kidneys, uterus,
      brain and skeletal muscles were collected and processed for conventional
      histopathology. In the early infection the major necropsy findings were focal
      haemorrhages on the intestinal wall, liver, lungs and brain. Histologically,
      larvae were found in haemorrhagic areas. In the subacute-chronic infection white
      nodules were scattered through all the examined organs, except the brain.
      Histologically, the white nodules corresponded to granulomas containing larvae
      surrounded by lymphocytes, eosinophil leukocytes and macrophages. The migration
      of B. transfuga larvae in spleen, kidneys and uterus of infected mice appears to
      have not been reported by previous workers. The possible role of B. transfuga
      larvae in the Visceral Larva Migrans syndrome is discussed.

PMID- 7638004
TI  - Zoonotic filaria of possible American origin in Italy.
AB  - From a 31 year old man, resident in Monfalcone (Venezia Giulia) a nodule in the
      right temporal region was surgically removed in January 1992 containing a
      filiform living nematode. On the basis of the morphological characters, the
      nematode proved to be Dirofilaria sp. subgenus Nochtiella but the exact species
      was not possible to define. The medical history indicated that the patient had
      spent the last summer in Florida.

PMID- 7638006
TI  - Transmission of Ureaplasma urealyticum from mothers to full and preterm infants.
AB  - This study assessed maternal genital colonization and subsequent neonatal
      transmission rate of Ureaplasma urealyticum in pregnant women in an average
      socioeconomic population. In addition very low birth weight infants were assessed
      to determine whether the presence of U. urealyticum correlated with increased
      risk of developing respiratory problems. The study group consisted of 108
      sequential full term mothers and 104 preterm mothers delivering in a tertiary
      care hospital in central Canada. The genital carriage rates (assessed using
      placental sampling) of ureaplasmas in term and preterm mothers were 25.9 and
      19.2%, respectively (P = 0.3185). Acquisition of ureaplasmas in the neonatal
      respiratory tract of neonates occurred significantly (P = 0.0182) more often in
      preterm neonates (11 of 130; 8.5%) than in term neonates (2 of 110; 0.9%). Very
      low birth weight (VLBW) infants (< or = 1500 g) were at greater risk (P = 0.042)
      of acquiring ureaplasmas in their respiratory tracts (5 of 26; 19%) than larger
      preterm neonates (6 of 104; 5.8%). All VLBW infants with respiratory colonization
      by ureaplasmas (5 of 5) developed bronchopulmonary dysplasia compared with 33% (7
      of 21) of VLBW neonates without ureaplasmas (P = 0.028). This difference in
      bronchopulmonary dysplasia development among VLBW infants was independent of
      further stratification by birth weight. These VLBW neonates with ureaplasmas also
      stayed significantly (P = 0.037) longer in the neonatal intensive care unit (43.6
      +/- 10.4 days) than did other preterm neonates (22.1 +/- 20.8 days). Our results
      demonstrate that VLBW preterm neonates have increased risk of acquiring U.
      urealyticum.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7638007
TI  - Efficacy of measles vaccine during the 1993 measles epidemic in Korea.
AB  - Immunization to eliminate measles is recommended at 15 months of age with the
      option of giving vaccine at 6 to 9 months of age during measles outbreaks in
      Korea. Because of the recent resurgence of measles and concern about the
      possibility of reduced vaccine efficacy caused by genomic differences between
      vaccine virus and contemporary wild measles viruses, we conducted a measles
      vaccine efficacy study involving children with household exposure ages 1 to 5
      years during measles outbreak that had occurred 1993 in Seoul and Seong-nam city,
      with the demographic analysis of patients brought to the hospitals. A total of
      380 patients (M:F = 216:164) were included in this study. Two hundred nine cases
      (55.0%) occurred in children less than 5 years of age, and 167 (43.9%) were
      younger than 16 months of age. The recorded age-specific incidence rates showed
      bimodal patterns, i.e. highest peak in those below 16 months of age and second
      peak in those ages 6 to 9 years of age. Only 9.6% (16 of 167) of the measles
      cases less than 16 months, 59.5% (25 of 42) of those 16 months to 4 years and
      91.8% (157 of 171) of the cases in school age children have been vaccinated.
      Attack rates among the 122 vaccinated siblings and 12 unvaccinated siblings ages
      1 to 5 years who contacted measles were 5.7 and 75%, respectively, and the
      clinical vaccine efficacy was 92.4% (95% confidence interval, 83.6, 96.4). The
      high vaccine efficacy in household exposures suggests that measles outbreaks in
      Korea are not caused by reduced vaccine efficacy.

PMID- 7638008
TI  - The immunogenicity of Haemophilus influenzae type b conjugate (HbOC) vaccine in
      human immunodeficiency virus-infected and uninfected infants.
AB  - Enzyme-linked immunosorbent assay polyribosyl ribitol phosphate (PRP) antibody
      responses to Haemophilus influenzae type b conjugate vaccine (HbOC) given at 2, 4
      and 6 months of age were retrospectively compared in 23 human immunodeficiency
      virus (HIV) and 24 non-HIV-infected infants. HIV-infected infants were divided
      into those who were P1 (asymptomatic) or P2 (symptomatic) by 1 year of age. The
      P2 group was further divided into P2A (mildly symptomatic) and > P2A (rapidly
      symptomatic) by 1 year of age. The post-third HbOC dose geometric mean antibody
      titer to PRP was significantly lower in 12 P2 infants (0.43 microgram/ml) than
      either the 11 P1 infants (5.03 micrograms/ml, P < 0.05) or the 24 non-HIV
      infected infants (3.43 micrograms/ml, P < 0.05). Within the P2 group, the
      geometric mean antibody titer to PRP was significantly higher in 5 P2A infants
      (1.63 micrograms/ml) compared with 7 infants who were > P2A (0.17 microgram/ml, P
      < 0.05). After the third HbOC dose, PRP antibody titers were > or = 1.0
      micrograms/ml for 4 of 12 P2 compared with 9 of 11 P1 infants (P < 0.05). Within
      the P2 group, PRP antibody titers were > 1.0 micrograms/ml for 4 of 5 P2A
      compared to 0 of 7 infants who were > P2A (P < 0.05). HIV-infected infants with
      PRP antibody titers > or = 1.0 micrograms/ml after the third HbOC dose had
      significantly higher mean CD4 counts (2842 cells/mm3) at the time of the third
      HbOC dose than those with lower PRP titers (1655 cells/mm3) (P < 0.05).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7638009
TI  - Outcome of children after maternal primary Toxoplasma infection during pregnancy
      with emphasis on avidity of specific IgG. The Study Group.
AB  - Congenital toxoplasmosis results from maternal primary infection during
      pregnancy. In our serologic screening study 42 of 16,733 pregnant women had
      findings suggestive of primary infection. Here we document the outcome of their
      offspring, 37 of 39 liveborn children. After 12 months postnatally, serologically
      verified congenital toxoplasmosis appeared in 4 children. All these children had
      persisting IgG at the age of 12 months by both the dye test and the IgG enzyme
      linked immunosorbent assay. All the congenitally infected infants had also
      specific IgM and IgA and showed significant increases in avidity of specific IgG
      during the 12-month follow-up. One of them had a unilateral retinal scar and
      intracranial calcifications. An additional 3 infants of the mothers with primary
      infection during early pregnancy presented with unilateral retinal scars but
      without seroresponses during the first 12 months of life. Maternal high avidity
      of IgG during the first trimester is a strong indicator against primary infection
      during pregnancy; the fetuses of such mothers are at low risk for congenital
      toxoplasmosis.

PMID- 7638010
TI  - Accuracy of leukocyte indices and C-reactive protein for diagnosis of neonatal
      sepsis: a critical review.
AB  - To evaluate the value of C-reactive protein and leukocyte indices in the workup
      of patients suspected of having infection in a neonatal intensive care setting, a
      literature search was conducted in all languages using MEDLINE (1966 to May,
      1994), EMBASE (1988 to May, 1994), bibliographic lists of primary and review
      articles and personal files. Citations identified as potentially relevant were
      reviewed by two independent investigators; only studies meeting preset criteria
      for population, diagnostic test and data presentation were included. Two
      observers independently assessed studies using explicit methodologic criteria.
      All data from the articles were extracted by one observer, whereas the second
      reviewer checked these data for accuracy. Four of the selected studies dealt with
      leukocyte count and ratios. The chi square test for homogeneity of proportions
      revealed significant heterogeneity across studies (P = 0.014 for the ratios; P <
      0.001 for white blood cell count), suggesting that test properties varied widely
      across studies. Fifteen of the selected studies evaluated C-reactive protein; of
      these six were qualitative using a latex agglutination method. Among these
      studies the chi square test for homogeneity of proportions was highly significant
      (P < 0.01), reflecting the great heterogeneity across studies. Among the nine
      studies that evaluated five different quantitative methods heterogeneity was
      again present (P < 0.001). Because of the striking heterogeneity among the
      studies evaluated, pooling to give a summary point estimate of the sensitivity
      and specificity of the various studies was not possible and the results are
      reported as ranges.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7638011
TI  - Pseudomonas aeruginosa infection in very low birth weight infants: a case-control
      study.
AB  - The perinatal histories and hospital courses of all neonates born at Grady
      Memorial Hospital who developed Pseudomonas aeruginosa sepsis or meningitis in
      the 5-year period 1989-1993 were reviewed. In addition a case-control study was
      performed to evaluate selected risk factors for this infection. Twenty-one
      patients had one or more blood cultures positive for P. aeruginosa. An additional
      patient had P. aeruginosa meningitis without bacteremia. All infections occurred
      after 5 days of age. The overall incidence of P. aeruginosa infection was
      0.7/1000 live births. All cases occurred in infants < 1500 g at birth, for a
      birth weight-specific rate of 19.5/1000 livebirths in this weight class. Clinical
      manifestations of disease did not distinguish P. aeruginosa from other causes of
      fulminant neonatal sepsis. Fifty percent of cases died. Mortality was inversely
      related to postnatal age at diagnosis. The 22 cases were compared with 44
      controls matched for birth weight, gestational age, sex, duration of hospital
      stay and admission date. Cases were more likely than controls to have a history
      of feeding intolerance, interrupted enteral intake and prolonged parenteral
      hyperalimentation. Case infants received intravenous antibiotics for a
      significantly longer period of time than did controls. There was an association
      between P. aeruginosa sepsis and necrotizing enterocolitis (36% cases vs. 7% of
      controls had prior or concurrent necrotizing enterocolitis, P < 0.01). In summary
      P. aeruginosa sepsis is primarily a late onset nosocomial infection in very low
      birth weight infants. The case fatality rate of 50% in this series emphasizes its
      continued importance.

PMID- 7638012
TI  - The family pet as an unlikely source of group A beta-hemolytic streptococcal
      infection in humans.
AB  - This study examines the possibility of the family pet serving as a reservoir for
      group A beta-hemolytic streptococcal infections in humans. We obtained
      oropharyngeal cultures from children with acute pharyngitis and concurrent
      oropharyngeal cultures from their household pets. Children with culture-proved
      group A beta-hemolytic streptococcal pharyngitis were detected in 26 of 42
      households surveyed. Oropharyngeal cultures were also collected from a group of
      children without pharyngitis and their pets. Additionally 149 dogs and cats from
      a local veterinary hospital were cultured from 371 body sites including the
      oropharynx, axilla and vagina. All beta-hemolytic bacterial isolates were
      identified by colonial and microscopic morphology, catalase and
      pyrrolidonylarylamidase production, bacitracin susceptibility and serogrouping.
      No group A beta-hemolytic streptococci were recovered from any of the body sites
      surveyed from a total of 230 animals. Based on these findings, the family pet
      seems to be an unlikely reservoir for group A beta-hemolytic streptococci.

PMID- 7638013
TI  - Maternal acceptance of voluntary human immunodeficiency virus antibody testing
      during the newborn period with the Guthrie card.
AB  - In order to provide the opportunity for women delivering newborns to have human
      immunodeficiency virus (HIV) testing we piloted a hospital-based voluntary HIV
      testing program during the newborn period using the Guthrie card. During the
      study period 789 women were offered newborn HIV antibody testing. Test acceptance
      during the newborn period (61.0%) was comparable to that reported for the
      prenatal period (60.6%). Overall 77.4% of women were tested in the newborn period
      or reported being tested in the prenatal period. Prenatal test acceptance best
      predicted newborn HIV test acceptance (odds ratio, 3.37; 95% confidence interval,
      2.40 to 4.74). When compared to HIV testing during the newborn period prenatal
      HIV testing is preferable because it enables the recognition of HIV infection
      early during pregnancy and allows the mother the option to elect zidovudine
      therapy and potentially prevent infection in her newborn. However, when prenatal
      HIV testing is not routinely made available or cannot be assured, women should be
      offered the opportunity to be tested during the newborn period.

PMID- 7638014
TI  - Seroreversion in human immunodeficiency virus-exposed but uninfected infants.
AB  - The goal of this study was to describe seroreversion (SR) in a cohort of human
      immunodeficiency virus-exposed but uninfected infants. Groups of patients who
      seroreverted very early or late were examined for salient clinical and
      immunologic characteristics of the mother or infant. The mean time (+/- s.d.) to
      seroreversion by enzyme-linked immunoabsorbent assay (ELISA) was 50.1 +/- 14.8
      weeks, or 11.6 months (n = 84); the range of times to antibody loss by ELISA was
      17.9 to 82.0 weeks. The mean time to seroreversion by Western blot was 68.3 +/-
      12.6 weeks, or 15.8 months (n = 51), with a range of 44.9 to 94.1 weeks. Initial
      anti-human immunodeficiency virus titer as measured by cord blood ELISA optical
      density (OD) was found to relate significantly to mean time to seroreversion. No
      relationship to time to seroreversion was demonstrated for gestational age,
      maternal or neonatal serum immunoglobulin concentrations, maternal CD4 cell
      counts, maternal alcohol consumption, infantile diarrhea or failure to thrive.
      The lengthy time to seroreversion seen here demonstrates the 1994 revised Centers
      for Disease Control and Prevention definition of human immunodeficiency virus
      infection (based on seropositivity by both ELISA and confirmatory tests
      persisting beyond 18 months of age) to be accurate in our population. We
      recommend Western blot testing be used as confirmation for positive ELISAs only
      after 18 months of age.

PMID- 7638016
TI  - A pseudoepidemic of tuberculin skin test conversions caused by a particular lot
      of purified protein derivative of tuberculin test solution.

PMID- 7638015
TI  - Pertussis caused by an erythromycin-resistant strain of Bordetella pertussis.

PMID- 7638017
TI  - Gastrointestinal perforation complicating meningococcal disease.

PMID- 7638018
TI  - Intestinal anthrax in a two-year-old child.

PMID- 7638019
TI  - Two cases of disseminated cutaneous herpes zoster in infants after intrauterine
      exposure to varicella-zoster virus.

PMID- 7638021
TI  - Medical management of Candida-infected thrombosis in a pediatric oncology
      patient.

PMID- 7638020
TI  - Moraxella catarrhalis ventriculitis in a child with hydrocephalus and an external
      ventricular drain.

PMID- 7638022
TI  - Severe pneumonia and chronic lung disease in a young child with adenovirus and
      Bordetella pertussis infection.

PMID- 7638024
TI  - Group A streptococcal susceptibilities.

PMID- 7638023
TI  - Acute renal failure in a human immunodeficiency virus-infected child secondary to
      bilateral fungus ball formation.

PMID- 7638025
TI  - Varicella prevalence in day-care centers.

PMID- 7638026
TI  - Thrombocytopenic purpura associated with primary human herpesvirus 6 infection.

PMID- 7638027
TI  - Physical signs in childhood pneumonia.

PMID- 7638028
TI  - Neonatal brucellosis.

PMID- 7638029
TI  - Management of infants born to mothers who have Chlamydia infection.

PMID- 7638030
TI  - Antimicrobial therapy issues facing pediatricians.
AB  - In the field of infectious diseases, the emergence of new pathogens or old
      diseases in newly recognized forms; changing virulence of pathogens; changing
      patterns of antimicrobial susceptibility; new diagnostic techniques, drugs or
      vaccines; changing concepts of chemoprophylaxis; controversies about medical vs.
      surgical techniques; and the challenge of care of children with infectious
      diseases within new guidelines of managed care are recently identified areas of
      change. The increased resistance of Streptococcus pneumoniae to many commonly
      used antimicrobials and the increased proportion of beta-lactamase-producing
      nontypable Haemophilus influenzae and Moraxella catarrhalis concern many
      practitioners. The decreased antibiotic susceptibility of S. pneumoniae is a
      relatively new phenomenon in the United States. Optimal therapy for mild,
      moderate or severe pneumococcal disease is dependent on current local
      susceptibility patterns. Group A streptococci are uniformly susceptible to
      readily achieved concentrations of all penicillins and cephalosporins. However,
      recent clusters of cases of rheumatic fever, increased recognition of toxic shock
      syndrome and bacteremic and localized severe pneumococcal disease have increased
      concern about the changing ecology of the Streptococcus and the implications for
      therapy. Finally recognition that many children with acute bacterial otitis media
      have resolution of disease without use of antimicrobial agents has led to more
      rigorous study designs for evaluating new drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7638031
TI  - Resistance among problem respiratory pathogens in pediatrics.
AB  - During the past two decades, the prevalence of beta-lactamase production with
      nontypable strains of Haemophilus influenzae has increased to about 35%.
      Fortunately, rates of resistance to other oral antimicrobials have not developed
      at a comparable pace. Amoxicillin/clavulanate, cefuroxime and cefpodoxime remain
      nearly uniformly active whereas rates of resistance to tetracycline,
      trimethoprim/sulfamethoxazole, chloramphenicol, cefaclor, loracarbef, cefprozil,
      azithromycin and clarithromycin remain low (1 to 5%). Virtually all clinical
      isolates of Moraxella catarrhalis produce beta-lactamase and are probably
      resistant to ampicillin and amoxicillin. However, alternative oral antimicrobials
      are almost always active. A compelling problem facing pediatricians today is the
      emergence of penicillin resistance with clinical isolates of Streptococcus
      pneumoniae. Currently, 15 to 25% of pneumococcal isolates in the United States
      have either intermediate (10 to 20%) or complete (3 to 5%) penicillin resistance
      caused by alterations in penicillin-binding proteins. Loss of activity of other
      beta-lactams is observed with penicillin-resistant S. pneumoniae. Third
      generation cephalosporins retain sufficient activity to warrant use in selected
      pneumococcal infections, even those caused by completely penicillin-resistant
      strains. Unfortunately, strains of S. pneumoniae with further alterations in
      penicillin-binding proteins have emerged such that even extended spectrum third
      generation cephalosporins lack activity. Rates of resistance to non-beta-lactam
      agents are also changing. The consequence of these changing patterns of
      resistance is that therapeutic options for pneumococcal infections in some
      patients are becoming increasingly limited.

PMID- 7638032
TI  - Emergence of resistant Streptococcus pneumoniae: a problem in pediatrics.
AB  - Penicillin resistance among strains of Streptococcus pneumoniae has emerged as an
      important worldwide problem. Beta-lactam-resistant pneumococci also can be
      resistant to erythromycin, trimethoprim/sulfamethoxazole and tetracycline and are
      uniformly susceptible to vancomycin and imipenem. Crowded conditions (e.g.
      daycare centers, hospitals, military barracks and prisons) and prior beta-lactam
      antibiotic therapy are the principal predisposing factors to colonization and
      disease. To date the two conditions caused by penicillin- and cephalosporin
      resistant pneumococci that have been especially difficult to treat are acute
      otitis media and meningitis. Concentrations of beta-lactams in cerebrospinal
      fluid and middle ear fluid are usually inadequate to achieve prompt eradication
      of some intermediately resistant and most highly resistant pneumococcal strains.
      Use of unconventional therapeutic agents such as ceftriaxone or clindamycin for
      acute otitis media and vancomycin or rifampin for meningitis may be necessary.
      Control of this global problem will require innovative methods to reduce the
      selective pressure that results from widespread antibiotic use and to develop
      effective pneumococcal vaccines that are immunogenic in young infants.

PMID- 7638033
TI  - Treatment guidelines for otitis media: the need for breadth and flexibility.
AB  - The recent issuance of guidelines for the diagnosis and treatment of otitis media
      with effusion in young children is an effort to provide direction for the
      practitioner in managing this common condition. Although the guidelines may often
      prove helpful, practitioners will need to maintain some degree of flexibility in
      dealing with patients both with acute otitis media and with otitis media with
      effusion, based on specific patient-related and disease-related factors.

PMID- 7638034
TI  - Perspectives on newer oral antimicrobials: what do they add?
AB  - Since oral antimicrobials have been commercially available, the few select
      compounds of the 1950s have evolved into an array of choices from the multiple
      classes currently approved for human use. This proliferation resulted primarily
      from the need for extended spectrum antimicrobials because of changing resistance
      patterns among established pathogens and emergence of new pathogens. However, it
      is not clear that newer oral cephalosporins, fluoroquinolones or macrolides
      necessarily provide clear advantages over existing drugs for many common or
      routine infections. Other goals of new drug development include minimizing
      adverse events and improving convenience. The dilemma facing clinicians is when
      to use these new or soon to be released compounds. This presentation addresses
      these and other questions as the elusive search for the ideal oral antimicrobial
      continues.

PMID- 7638035
TI  - Present and future challenges of immunizations on the health of our patients.
AB  - A recent analysis demonstrated a change in incidence approaching 100% for
      diseases against which we routinely immunize in the United States. At present,
      measles, mumps, rubella, invasive Haemophilus disease, poliomyelitis, diphtheria
      and tetanus are well-controlled but not eliminated. Diseases that now pose
      special problems include pertussis, hepatitis A and B and varicella. The
      incidence of pertussis surged in 1994, possibly in part because of waning
      immunity in the immunized population. Acellular pertussis vaccines are available
      for booster doses in children but are not now recommended for adults. Licensure
      of acellular pertussis vaccines for primary immunization of infants is eagerly
      awaited. Recombinant hepatitis B vaccine has been licensed for more than 10 years
      but there has been little change in disease incidence in the United States.
      Routine immunization of infants is now recommended but concerns exist about cost
      and persistence of immunity into adolescence. Inactivated hepatitis A vaccines
      appear to be highly effective in preventing clinical hepatitis and controlling
      epidemics. Potential target populations include military personnel, day-care
      attendees and travelers. Hepatitis A vaccine may be recommended for all children
      after approval by the United States Food and Drug Administration and if a
      combination vaccine becomes available. A live, attenuated varicella vaccine
      developed in 1974 and unlicensed in the United States is safe and highly
      effective in preventing varicella in healthy and immunocompromised populations.
      It also appears to reduce subsequent development of herpes zoster. Vaccines
      against pneumococci (conjugate vaccine), respiratory syncytial virus, rotavirus,
      tuberculosis and human immunodeficiency virus are needed. Research and technology
      to develop these vaccines must be developed, and efficient delivery mechanisms
      must be created and implemented.

PMID- 7638036
TI  - Mitotic delay in peripheral blood lymphocytes and fibroblast cultures obtained
      from a child with Down's syndrome and from a healthy child.
AB  - Mitotic delay (MD) often occurs in cells of donors exposed in vivo to genotoxic
      agents. To investigate individual sensitivity with genetic background, author
      measured the 3-methyl-cholanthrene (MC)-induced MD in cultured human skin
      fibroblasts (FBs) and in peripheral blood lymphocytes (PBLs) obtained from a 4
      year-old patient with Down's disease. Samples from a 10-year-old healthy subject
      served as controls. Skin samples were obtained during surgical intervention. The
      induced MD was calculated from the mitotic index (MI) which was expressed in per
      cent of the control; at various times up to 18 h after treatment. Cells were
      treated with 10(-7), 10(-6) and 10(-5) M MC (with S-9 liver homogenate). At
      passage 10, the average MI (+/- SE) was 8.32 +/- 0.43%, and 7.85 +/- 0.64% for
      the healthy and for the Down's FBs, respectively; and it was 4.89 +/- 0.59%, and
      4.92 +/- 0.72% for the healthy and for the Down's PBLs, respectively. MD was
      characterized as 50% MI of control (MD50). The MD50 values were the most
      expressed when cells were treated with 10(-5) M MC. No difference was found in MD
      of healthy and Down's fibroblasts. For Down's lymphocytes, on the other hand, MD
      was approximately 30% longer than for healthy cells. This result agrees well the
      reported increased SCE and decreased DNA-repair data obtained in PBL of Down
      patients.

PMID- 7638037
TI  - The reaction of adenohypophysis hormones in primary hyperparathyroidism and after
      surgical treatment.
AB  - The anterior pituitary hormone serum levels of 13 patients of both sexes were
      examined for basal secretion and response to TRH-GnRH stimulus before and after
      parathyroidectomy. The patients were suffering from hyperparathyroidism of
      parathyroid adenoma origin. After the operation, the previously high serum
      calcium and low serum phosphate levels decreased (P < 0.001). The serum
      parathyroid hormone (PTH) concentration, too, decreased significantly. After
      surgery, the basal and stimulated secretion of thyrotropin (TSH) showed a
      significant increase (P < 0.02 and P < 0.05, respectively). Significantly higher
      prolactin (PRL) levels were measured after surgery in those patients whose PRL
      levels were normal both before and after the operation. No significant change was
      observed in patients with hyperprolactinaemia. After surgery an increased
      spontaneous growth hormone (GH) secretion was found, while the basal luteinizing
      hormone (LH) and follicle-stimulating hormone (FSH) secretions remained
      unchanged. In postmenopausal women the stimulated FSH secretion decreased (P <
      0.05), while the decrease of the stimulated LH secretion was not significant. The
      results suggest that extracellular calcium may modify the secretion of certain
      adenohypophysis hormones and their stimulus-induced response.

PMID- 7638038
TI  - Atrial natriuretic peptide (ANP) responsiveness in patients with hypothyroidism.
AB  - Hypothyroidism is known to be associated with abnormalities of kidney function;
      recently, low atrial natriuretic peptide (ANP) plasma levels have been reported.
      Aim of the study was to asses ANP, sodium and water responsiveness to an acute
      saline load. Twelve patients with established primary hypothyroidism and 9
      control subjects were studied. ANP was determined in plasma by RIA with
      extraction, prior to and after the infusion of saline, 500 ml/h for 4 hours. On a
      similar albeit liberal sodium diet hypothyroid patients excreted less sodium and
      water (74 +/- 33 (SD) mumol/min and 0.69 +/- 0.15 ml/min, respectively) than
      control subjects (110 +/- 52 mumol/min; P < 0.05 and 1.06 +/- 0.53 ml/min; P <
      0.025, respectively). However, the infusion of saline resulted in a 3-fold
      increase of sodium output and more than 2-fold increase in urine flow. The
      exaggerated responsiveness in sodium excretion in patients with hypothyroidism
      was associated with significantly decreased pre-infusion ANP plasma levels (16.1
      +/- 11.1 pg/ml vs. 44.4 +/- 14.4 pg/ml; P < 0.001) and also with sluggish
      response to the volume expansion (+24% vs. +48%). A significant correlation was
      found between serum T4 levels and plasma ANP concentrations in 8 patients (r =
      0.689; P < 0.05). Although hypothyroid patients tend to retain sodium on a
      liberal salt diet, their kidney is capable of vigorously eliminating excess
      sodium when challenged with an acute saline load. This exaggerated responsiveness
      of sodium excretion can be demonstrated in spite of a sluggish response in ANP.
      Subnormal ANP levels in hypothyroidism are probably the result of thyroid
      deficiency.

PMID- 7638039
TI  - Hypothalamic dysfunction in Parkinson's disease patients.
AB  - Ten patients with idiopathic Parkinson's disease (PD) (3 men and 7 women, group
      A) who had received no treatment for the disease; 102 patients with PD (36 men
      and 66 women, group B) who had undergone treatment and 45 healthy volunteers (15
      men and 30 women, control group) were subject to thyrotropin-releasing hormone
      (TRH) tests and levodopa tests. In group A basal plasma prolactin (PRL) levels
      were significantly higher than in the controls both before and during treatment.
      Peak plasma PRL levels during TRH tests were significantly higher before
      treatment, but returned to the control levels during treatment. Nadir plasma PRL
      levels during levodopa tests were significantly increased before and during
      treatment. In group B basal plasma thyroid-stimulating hormone (TSH) and PRL
      levels were significantly higher than in the control group. Peak plasma PRL
      levels during TRH tests and nadir plasma PRL levels during levodopa tests were
      also significantly increased. The results strongly suggest a disturbance of
      pituitary hormone secretion due to hypothalamic dysfunction in PD patients.

PMID- 7638040
TI  - Characteristics of long QT with permanent bradycardia.
AB  - The study was aimed to investigate the electrophysiological properties of long QT
      syndrome associated with permanent bradycardia. The investigations were performed
      in 26 patients suffering from long QT duration (QTC-frequency adapted QT-:484 +/-
      34 ms) with permanent, marked bradycardia (heart rate: 42 +/- 7 min-1). Adams
      Stokes syncopal attack appeared in 12 patients, while in 14 cases ventricular
      tachycardia attack with syncope could be observed (study group). As control
      served the data of 30 patients suffering from long lasting marked bradycardia
      (heart rate: 44 +/- 7 min-1) with normal QT (QTC:420 +/- 28 ms). Each patient was
      candidate for pacemaker implantation. The following questions were studied: 1.
      The effect of heart rate on QT duration. The experiments were performed by
      electrical ventricular stimulation. 2. The effect of sympathetic and
      parasympathetic-pharmacologic-blockade on QT time. The study was performed under
      electrical ventricular stimulation by administration of propranolol and atropine.
      3. The dispersion of QT time was studied by using electrical heart stimulation
      and 12 lead ECG recording. Electrophysiological investigations were performed in
      14 patients with long QT and permanent bradycardia. On augmentation of the cycle
      length (bradycardia) the increase in the QT duration was more-out of all
      proportion-expressed in long QT. On pharmacologic sympathetic blockade in long QT
      syndrome the QT duration significantly diminished. The QT dispersion was more
      expressed in patients with prolonged QT interval and on bradycardia the QT
      dispersion further increased significantly. The irritability of the ventricle was
      markedly augmented in patients with long QT and bradycardia. Appearance of
      polymorphous ventricular tachycardia could frequently be observed and could be
      regularly induced by early ventricular extrastimuli and bradycardia.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7638041
TI  - Analysis of re-entry mechanism in a patient with concealed Wolff-Parkinson-White
      syndrome.
AB  - This report deals with a patient with concealed Wolff-Parkinson-White syndrome in
      whom both narrow and wide QRS tachycardias were observed. The simultaneous
      occurrence of various QRS morphology during supraventricular tachycardia results
      in a challenging diagnostic ECG problem. The cycle length during tachycardia with
      left bundle branch block was longer than the cycle length during narrow QRS
      supraventricular tachycardia and with functional right bundle-branch block.
      Electrophysiologic studies revealed an increased V-A conduction time during
      tachycardia with left bundle branch block. These studies suggested the presence
      of a concealed left-sided anomalous pathway. Differentiation between intra- and
      extranodal re-entry and therapeutic modalities are also discussed.

PMID- 7638042
TI  - Pathophysiological aspects of the protective effect of magnesium in myocardial
      infarction (review).
AB  - Intravenous administration of magnesium has proved to have beneficial effect in
      acute myocardial infarction. Magnesium seems to act at different levels of the
      cardiovascular system. Of the greatest importance is the direct influence of Mg2+
      on the cardiomyocyte which includes: reduction of cytoplasmatic calcium overload,
      protection of mitochondria against calcium influx, and diminution of cellular
      potassium, magnesium and ATP depletion. By means of these effects, or by its
      direct action on myocardium, Mg2+ inhibits the origin of postinfarctional
      dysrhythmias. Furthermore, magnesium reduces afterload by decrease in vascular
      resistance, and improves coronary flow. The mechanism underlying the protective
      effect of magnesium remains complex and poorly understood. Nevertheless, Mg2+
      therapy is effective, undemanding, and easy to procure. Expectably, intravenous
      administration of Mg2+ may become a routine part of myocardial protection in
      acute myocardial infarction.

PMID- 7638043
TI  - Polymorphic paracetamol conjugation: phenotyping in a Hungarian population.
AB  - The authors studied the distribution of the paracetamol conjugation in a
      Hungarian population (53 adult Caucasian persons). The data indicated that the
      excretion of paracetamol glucuronide and sulphate were not normally distributed.
      Bimodality were apparent in both conjugation pathways: 15.1% of subjects was
      relatively extensive glucuronidators, and the 24.5% of subjects was extensive
      sulphatators. Monitoring the ratios of various urinary paracetamol
      conjugates/paracetamol may be useful as a tool for determining the glucuronide
      and sulphate conjugation capacity in humans.

PMID- 7638044
TI  - Serum cholesterol profile of some Nigerian pregnant women.
AB  - A semi-longitudinal study of the cholesterol profiles at various stages of
      pregnancy was conducted. The study involved 49 pregnant women who showed no
      physical signs of obesity, were neither hypertensive nor diabetic, and had a mean
      age of 24.7 +/- 4.5 (mean +/- SD). The results showed a progressive increase in
      the serum total and high-density lipoprotein (HDL) cholesterol levels from 4.02
      +/- 0.39 mmol/L (mean +/- SD) and 1.81 +/- 0.15 mmol/L, respectively, at 3
      months, to 5.59 +/- 0.51 mmol/L and 2.46 +/- 0.18 mmol/ in the ninth month of
      pregnancy. These represent a 39 +/- 11% and a 35 +/- 10% increase in total and
      HDL cholesterol, respectively, over the 3-month level. The levels of total and
      HDL cholesterol however decreased to 4.08 +/- 0.40 mmol/L and 1.89 +/- 0.17
      mmol/L, respectively, a month after delivery. The most significant (P < 0.05)
      month to month increase was recorded between the 6th and the 7th month for both
      total and HDL cholesterol. The proportion of HDL cholesterol remained fairly
      constant at 43 +/- 3 to 45 +/- 4% throughout the period of pregnancy covered, and
      one month after delivery. This suggests a proportional increase in all
      lipoprotein fractions. It is concluded that the observed changes are normal
      physiological events.

PMID- 7638045
TI  - Myasthenia gravis: effect of immunoactive therapies.
AB  - New immunoactive therapies, plasmapheresis, intravenous steroid pulse infusion
      and intravenous immunoglobulins were examined for efficacy on the basis of large
      casuistics of myasthenia gravis. The best results were achieved with combination
      of these procedures. Indications of the new methods: (i) respiratory crisis of
      any character (myasthenic, cholinergic or mixed oscillating crisis); (ii) the
      patients' preparation for thymectomy; (iii) post-thymectomy therapy aimed at
      improving the patients condition, at avoiding relapses, at shortening the time of
      steroid therapy and at repressing cholinergic drug therapy; (iv) patients of old
      age in crisis-prone state. The new methods, together with thymectomy, steroid
      therapy and immunosuppression, represent a very efficient and promising new way
      toward modern therapy of myasthenia gravis.

PMID- 7638046
TI  - Polyphasic and protracted patterns of hepatitis A infection: a retrospective
      study.
AB  - The present study was performed in order to evaluate the frequency and clinical
      features of polyphasic and protracted forms of HA infection. Out of 297 adult HA
      patients admitted to our hospital, 12.5% and 8.4% were polyphasic and protracted,
      respectively, in clinical course. 21.6% of the polyphasic patients had more than
      one relapses. The rates of symptomatic relapse during the follow-up of the
      polyphasic and protracted HA infections were 51% and 56%, respectively, One % of
      all HA patients presented a cholestatic pattern. Three % of all the patients had
      to be readmitted for hospital treatment. The outcome of disease was benign in all
      HA patients, though, complete recovery sometimes needed six months.

PMID- 7638047
TI  - The use of urine protein 1 as an indicator of renal tubular function in type I
      (insulin-dependent) diabetes.
AB  - One hundred male insulin-dependent diabetic patients, aged 16 to 85 (mean 51.9)
      years, with albumin excretion ranging from normal to gross excess were examined
      for glomerular and tubular functional alterations by estimating urinary levels of
      albumin and indicator proteins of tubular damage. Urine protein 1 (UP1), a newly
      discovered low-molecular weight alpha-2 glycomicroglobulin, together with alpha 1
      microglobulin was used to assess tubular function. 19% of the patients showed
      increased albumin excretion with normal levels of tubular proteins (glomerular
      proteinuria), 11% excreted only tubular proteins in excess (tubular proteinuria),
      while 40% had a mixed pattern of both increased albumin and tubular proteins
      (glomerulotubular or mixed proteinuria). 30% had normal albumin and tubular
      protein excretion in urine. UP1 was found to be a more sensitive indicator of
      tubular abnormality than alpha 1-microglobulin. It is concluded that, although
      glomerular changes may be responsible for the proteinuria seen in most diabetics
      (mixed proteinuria), in a small but significant proportion of diabetics, tubular
      functional alteration may occur before, or in the absence of, glomerular
      dysfunction, and may warn of subclinical tubular abnormality. This finding may
      have a direct bearing on the development and course of progression of diabetic
      nephropathy, and may question the reliability of the present prognostic
      interpretation of microalbuminuria.

PMID- 7638048
TI  - [Prostate and prostatic carcinoma: comparison of gadolinium-enhanced MR images
      and histopathologic findings].
AB  - The purpose of this study was to determine the patterns of enhancement in normal
      prostate, and to compare them with the enhancement patterns and histopathologic
      findings in patients with prostatic carcinoma. Seventeen patients who had no
      urogenital disease and 27 who underwent radical prostatectomy or prostatic biopsy
      were included in this study. All patients were evaluated with T1-, T2-weighted
      and gadolinium-enhanced T1-weighted images. With gadolinium enhancement the inner
      gland showed more enhancement than the peripheral zone in the normal prostate.
      The carcinoma tissue was enhanced more than the peripheral zone in 13 patients,
      about the same as the peripheral zone in 11 patients, and less than the
      peripheral zone in three patients. The three patients whose cancer tissue
      demonstrated no enhancement had poorly differentiated adenocarcinoma of the solid
      type. In conclusion, gadolinium-enhanced T1-weighted imaging is not reliable for
      routine use in MR imaging of the prostate, but may be useful to evaluate
      histologic types in patients with prostatic carcinoma.

PMID- 7638049
TI  - [Contrast-enhanced 3D MR angiography of the chest and abdomen with breath-holding
      using phase reordering].
AB  - This report presents the feasibility of phase-recordered contrast-enhanced three
      dimensional MR angiography in 32 consecutive patients with vascular abnormalities
      in the chest and abdomen. To suppress motion artifacts due to respiratory
      corruption, a phase-reordering technique was introduced so that the low frequency
      components of the phase data were obtained first during the imaging period. Image
      quality and degree of motion suppression were assessed by four radiologists
      independently without information on breath-holding time. Abnormalities were
      detected in 30 cases (93.8%), and their extent was correctly assessed in 28 cases
      (87.5%). More confident assessment was possible in abnormalities of the pulmonary
      vessels and thoracic aorta than in those of the abdominal aorta and portal venous
      system. With phase reordering, more than 20 seconds of breath-holding ensured
      image quality sufficient to correctly assess the vascular abnormalities. While
      this technique is easy and requires only single breath-holding, it can provide
      excellent MRA without slice-to-slice spatial misregistration.

PMID- 7638050
TI  - [MR imaging of infected spondylodiskitis: interval signal change in vertebral
      body (including enhanced image of vertebral body)].
AB  - A retrospective evaluation of MRI was carried out in 22 patients with
      spondylodiskitis. Low signal intensity on T1-weighted images and high or low
      signal intensity on T2-weighted images were observed. Sixteen patients underwent
      follow-up examinations after the initial examination. Various signal changes in
      the vertebral body were recognized. The longer the period of follow-up, the less
      abnormal the signal intensity became on both T1- and T2-weighted images. Several
      cases showed no change in signal intensity. In all of 17 patients re-examined
      after injection of Gd-DTPA, infected vertebral bodies were enhanced. We
      classified the enhancing patterns of infected vertebral bodies in three types: A)
      homogeneous, B) homogeneous with strong enhancement adjacent to the end plate, C)
      inhomogeneous. Pyogenic spondylodiskitis tended to show patterns A or B, and
      tuberculous spondylodiskitis pattern C. The enhancement effect disappeared after
      normalization or remission of laboratory findings. In two cases, the enhancement
      effect remained even after laboratory findings became normal. Contrast MRI was
      useful for understanding infectious state.

PMID- 7638051
TI  - [Magnetic resonance imaging of renal lymphoma with computed tomography
      correlation].
AB  - The magnetic resonance (MR) imaging and computed tomography (CT) findings in four
      patients (five kidneys) with non-Hodgkin's lymphoma involving the kidneys and
      perirenal spaces are presented. The patterns of disease in each case were as
      follows: bilateral renal nodules, infiltration in the perirenal space,
      infiltration in the perirenal space with renal involvement, and direct invasion
      from contiguous retroperitoneum. On plain CT, the lesions showed slight
      hyperdensity (three kidneys) and isodensity (two kidneys) as compared with normal
      renal parenchyma. But all lesions appeared as hypodense masses with more definite
      margins after contrast enhancement. MR imaging findings showed iso- or slight
      hypointense masses on T1-weighted images and definite hypointense masses on T2
      weighted images as compared with the signal intensity of the renal cortex.
      Dynamic imaging and conventional delayed T1-weighted imaging following Gd-DTPA
      injection showed no significant enhancement of the lesions. In comparison with
      contrast enhanced CT, despite its poorer resolution, T2-weighted MR imaging
      showed nearly the same accuracy in the evaluation of number and extent of the
      lesions without contrast medium administration. MR imaging was also useful to
      evaluate the patency of vessel lumen surrounded by tumor mass and to determine
      the location and extent of huge lesions by its multiplanar imaging capabilities.

PMID- 7638052
TI  - [Object analysis of bone marrow MR imaging using double echo STIR sequence in
      hematological diseases].
AB  - The bone marrow of 84 patients with hematological disorders was investigated
      using short inversion time inversion recovery sequence (STIR) on an 1.5 Tesla
      superconducting MRI system. Double echo times of 20 and 100msec were applied to
      research the signal characteristics of the lesion and carry out quantitative
      analysis of the receiver operating characteristic curve (ROC). The hematological
      diseases included 19 cases of myelodysplastic syndrome (MDS), 18 of multiple
      myeloma (MM), 18 of chronic myelocytic leukemia (CML), 9 of aplastic anemia (AA),
      8 of acute myelocytic leukemia (AML), 3 of chronic lymphocytic leukemia (CLL), 3
      of myelofibrosis, and 3 others. Using STIR with double echo times, bone marrow
      showed high signal intensity (SI) on short TE and low SI on long TE in MDS and
      CML; high SI on short and long TE in myelofibrosis and CLL; high SI on short TE
      and high to moderately high SI on long TE in MM; and low SI on short and long TE
      in AA. Quantitative analysis of 33 patients showed high sensitivity and
      specificity in AA (81% and 94%, respectively) and moderate sensitivity and high
      specificity in MM (61%, 88%). CML and MDS were similar with low sensitivities
      (40%, 41%) and high specificities (80%, 78%). Differential diagnosis between CML
      and MDS was difficult using STIR with the double echo time method.

PMID- 7638053
TI  - [Non-Hodgkin's lymphoma of stage I and II in elderly patients: a retrospective
      study in comparison with younger patients].
AB  - Forty-one patients with non-hodgkin's lymphoma at stages I and II who had
      received radiation therapy were reviewed to analyze the prognosis and prognostic
      factors, with the main focus on a comparison of elderly (age > 65 years) and
      younger patients. In terms of clinical and histological characteristics, there
      were no differences between the elderly and younger patients. The 5-year-survival
      rate (5YS) in elderly patients was 52.8%, compared with 68.6% for younger
      patients. In patients treated with irradiation alone, the 5YS was 49.5% in
      elderly patients and 22.1% in younger patients. Combination treatment consisting
      of irradiation and chemotherapy improved 5YS markedly to 84.9% in the younger
      patients, while no apparent improvement was seen in the elderly patients, in whom
      5YS was 54.1%. Using Cox's multiregression life table, two prognostic factors,
      the presence of symptoms and LDH, were extracted and found to have a significant
      influence upon the survival of the elderly patients. Complete response was 90.2%
      in the elderly patients, although relapse was seen in 54.1% of the complete
      responders. Relapse occurred overwhelmingly outside the irradiated regions. Since
      the prognosis of elderly patients could not be improved with the current
      chemotherapy regimen, some different regimen must be established to lower the
      high relapse rate in the area outside the irradiated field.

PMID- 7638054
TI  - [Correlation analysis between patlak plot and DAR using 11C-methionine PET].
AB  - Seven patients were studied with positron emission tomography (PET) using 11C
      methionine. All had non-Hodgkin's lymphoma but one, who had Hodgkin's disease. By
      assuming a simple three-compartment model for dynamic data analysis, we used the
      graphic method proposed by Patlak et al., where Ki (K2K3/(K1+K3)) was compared
      with DAR (differential absorption ratio). Trichloroacetate was added to each
      plasma sample, and the activity of the acid-soluble fraction was counted to
      eliminate the influence of the protein-bound fraction of injected activity.
      Patlak data plots, using this acid-soluble fraction as an input factor, showed
      good linearity over the time of data collection. All tumors showed clear 11C
      methionine accumulation. Tumor activity reached almost a plateau within 10 min
      and was kept at the same level for at least 30 min. Ki and DAR were 0.070 +/-
      0.035 and 4.64 +/- 1.85 (mean +/- SD), respectively. There was no apparent
      correlation between histological type and Ki or DAR, while the correlation
      efficient between Ki and DAR was 0.875. Our conclusion is that DAR will give
      almost the same result as dynamic data in the analysis of methionine metabolism
      using PET.

PMID- 7638055
TI  - [Uptake of Tc-99m hexakis 2-methoxy isobutyl isonitrile in lung or mediastinal
      lesions by SPECT].
AB  - The uptake of Tc-99m hexakis 2-methoxy isobutyl isonitrile (99mTc-MIBI) was
      evaluated in 18 patients with various lung or mediastinal lesions by SPECT. The
      patients consisted of seven with lung cancers, three with lung cancers who were
      treated with chemotherapy and were disease free, and one each with malignant
      lymphoma, esophageal cancer, thyroid cancer involving the mediastinum, malignant
      thymoma, pneumonia, granuloma, sarcoidosis and neurinoma. SPECT imaging (30 min,
      600 MBq) was performed after intravenous injection. Strong uptake of 99mTc-MIBI
      was noted in all malignant tumors except malignant lymphoma. The mean tumor to
      normal lung tissue uptake ratio (T/N ratio) was 2.26. The mean in lung cancer was
      2.31. Slight accumulation was present in pneumonia and granuloma (mean T/N =
      1.24). No accumulation was present in a case of non-Hodgkin's lymphoma and
      neurinoma. Moderate uptake was noted in one case of sarcoidosis (T/N = 1.46). No
      abnormal accumulation of 99mTc-MIBI was seen in post-therapeutic lung cancer.
      These results suggested that 99mTc-MIBI SPECT could be useful in differentiating
      between malignant and benign lesions.

PMID- 7638056
TI  - [Stereotactic radiation therapy with linear accelerator: accuracy of alignment
      and portal film verification].
AB  - Stereotactic radiation therapy with a linear accelerator requires precise
      alignment of therapeutic radiation distribution to the target volume. To verify
      the accuracy of alignment, differences between the stereotactic coordinates of
      the center of the therapeutic radiation distribution determined from portal films
      and those of the target points determined from CT/MRI or CT/angiographic
      localization were calculated for 58 points. The average values and one standard
      deviation were--0.02 +/- 0.50mm, 0.37 +/- 0.39mm and 0.01 +/- 0.25mm in the x, y,
      and z directions, respectively. The average value of the total deviation was 0.73
      +/- 0.07mm. Potential sources of misalignment were misaligned laser pointers,
      wide laser beam width, improperly zeroed target positioner scale, and motion of
      the patient couch. The accuracy of alignment should be verified prior to
      irradiation. Portal film verification is indispensable for strereotactic
      radiation therapy with a linear accelerator.

PMID- 7638057
TI  - [A trial for quantification of proton MR spectroscopy: relaxation times of each
      metabolite and concentration using water signal as an internal standard].
AB  - We conducted quantification of proton MR spectroscopy (1H-MRS) using water signal
      as an internal standard. The 1H-MR spectrum was measured with and without water
      suppression pulses. For calculation of relaxation times, measurement conditions
      of the PRESS sequence were as follows: TR = 1500, 3000, 5000 ms, TE = 135,270 ms.
      The T1 relaxation and T2 relaxation of each metabolite were calculated by fitting
      to the curve of the equation of the spin echo sequence. The signal intensities of
      each metabolite were corrected using relaxation times and such corrected
      intensities were used for the quantitative calculation. The concentration of each
      metabolite was obtained from ratios of the corrected intensities of water and
      metabolites. The value of each concentration was coincident with that reported in
      the previous literature. We considered that this quantification using water
      signal as an internal standard would be very useful when the proton-weighted
      image does not show remarkable change.

PMID- 7638058
TI  - [Treatment with percutaneous transluminal balloon venoplasty for superior vena
      cava syndrome after permanent pacemaker implantation].
AB  - Superior vena cava (SVC) syndrome after transvenous implantation of a permanent
      pacemaker is relatively uncommon. We present a woman whose neck and face became
      swollen two years after implantation of a two-chamber pacemaker. Computed
      tomography and digital subtraction angiography revealed severe SVC stenosis.
      Percutaneous transluminal venoplasty (PTV) was performed to relieve the stenosis.
      PTV was effective to improve the swelling of her neck and face. PTV seems to be a
      good method to relieve SVC stenosis after implantation of a pacemaker.

PMID- 7638059
TI  - [Planning for brachytherapy using a 3D-simulation model].
AB  - A 3D-simulation model made with a milling system was applied to HDR
      brachytherapy. The 3D-simulation model is used to simulate the 3D-structure of
      the lesion and the surrounding organs before the actual catheterization for
      brachytherapy. The first case was recurrent prostatic cancer in a 61-year-old
      man. The other case was lymph node recurrence of a 71-year-old woman's upper gum
      cancer. In both cases, the 3D-simulation model was very useful to simulate the 3D
      conformation, to plan the treatment process and to avoid the risk accompanying
      treatment.

PMID- 7638060
TI  - [High dose rate fractionated interstitial radiotherapy for vulvar cancer using
      traction technique].
AB  - A 73-year-old woman with vulvar cancer T2NO was treated with high dose rate
      fractionated interstitial radiotherapy after 30 Gy of external radiotherapy.
      Sufficient space to insert 12 needles was made by pulling the vulva out
      perpendicular to the perineal skin. Four surgical threads were introduced between
      the vulva and the underlying pubic bones. A pair of custom-made templates were
      attached sandwiching the vulva pulled out with the threads. Using traction
      technique 12 stainless needles were easily inserted and replaced by plastic
      tubes. Forty Gy/10 fractions/six days was delivered, and the tumor has been
      controlled clinically and histologically so far.

PMID- 7638061
TI  - Having a slashing time.

PMID- 7638062
TI  - Managing asthma. Knowledge for practice. Part I.

PMID- 7638063
TI  - Sexual health and learning disabilities.

PMID- 7638064
TI  - Hard currency.

PMID- 7638065
TI  - Pulled strings.

PMID- 7638066
TI  - Labour chains.

PMID- 7638067
TI  - Raising awareness.

PMID- 7638068
TI  - The causes and incidence of haematological malignancies.
AB  - This paper considers the current state of knowledge about the causes, physiology
      and incidence of haematological disorders. An account of the controversy
      surrounding the incidence of paediatric leukaemias is discussed, together with
      details of research into environmental causes and their relationship to leukaemia
      in children.

PMID- 7638069
TI  - Caring for patients with chronic leukaemia.
AB  - Unlike the acute form, chronic leukaemia has a long disease progression,
      requiring care in the community as well as out-patient and in-patient treatment.
      This paper describes how effective communication and planning maintains
      continuity of care and enables the smooth transistion between different modes of
      treatment.

PMID- 7638071
TI  - Cautionary tales.

PMID- 7638072
TI  - The use of standard setting to improve maternity care.
AB  - High-quality care for mothers and babies is a priority for midwives. Achieving
      the best standards depends on systematic evaluation. This paper describes how
      staff at the Nottingham City Hospital Maternity Unit introduced standard setting
      in clinical areas and improved practice as a result.

PMID- 7638070
TI  - Making sense of the technique of venepuncture.
AB  - Venepuncture is a skill being undertaken by an increasing number of nurses. This
      paper describes the steps to be taken together with some of the measures employed
      to avoid problems.

PMID- 7638073
TI  - Client attachment in learning disabilities nurse education.
AB  - This paper describes the method by which the learning disabilities branch
      programme in Southampton has been adapted to reflect educational and practical
      changes. Emphasis is placed on integrating theory and practice through giving
      students extended contact with a caseload of patients with the support of a tutor
      and mentors. The authors report on the initial difficulties and benefits
      resulting from the new programme.

PMID- 7638074
TI  - Helping parents cope.

PMID- 7638075
TI  - A minor matter?

PMID- 7638076
TI  - Stress. Get ahead.

PMID- 7638077
TI  - Beds. Pressure-relieving devices.

PMID- 7638078
TI  - Who was Dupuytren?

PMID- 7638079
TI  - Conduct unbecoming.

PMID- 7638080
TI  - Accepting the inner voices.

PMID- 7638081
TI  - The illusion of progress.

PMID- 7638082
TI  - Differentiation-stage specific expression of oncoprotein 18 in human and rat
      prostatic adenocarcinoma.
AB  - Oncoprotein 18 (Op18) is an intracellular phosphoprotein that has been shown to
      be overexpression in a number of human malignancies. In the present report we
      have studied the pattern of Op18 expression on normal, hyperplastic, and
      malignant prostatic tissue as well as in rat prostatic tumor lines. One of the
      objectives of the present work was to establish whether the level of Op18
      expression can be used as a prognostic marker in human prostatic adenocarcinoma.
      To that end, sections from normal, hyperplastic, and malignant human prostatic
      tissue were examined by immunohistochemistry for expression of Op18. In the
      normal and hyperplastic prostate, Op18 expression was observed in basal glandular
      epithelial cells, whereas the columnar luminal epithelial cells were not stained
      by the anti Op18 antibodies. In highly differentiated prostatic cancers
      occasional epithelial cells were stained, while in poorly differentiated tumors
      most of the epithelial cells contained Op18 immunoreactivity. The staining
      pattern was similar in the primary prostatic tumor and in the regional lymph node
      metastases. Most importantly, a limited survey of prostatic cancer patient
      samples (n = 40) showed a significant correlation between the fraction of Op18
      immunoreactive cells and survival. Studies of a rat prostatic tumor model, showed
      that only a few cells were stained in the highly differentiated Dunning R3327PAP
      tumor, while most cells were stained in the anaplastic AT1 rat prostatic tumor.
      Interestingly, castration of rats resulted in an increased Op18 immunoreactivity,
      within 14 days, in the highly differentiated rat R3327PAP prostatic tumor. In
      conclusion, the level of Op18 expression seems to be related to cellular
      differentiation, histological grade, and survival in prostatic cancers. These
      findings show that Op18 immunoreactivity may be useful as a prognostic marker in
      prostatic cancer. In addition it may help in the differentiation between highly
      differentiated prostatic tumors and non-malignant conditions.

PMID- 7638083
TI  - Nuclear morphometry is of independent prognostic value only in T1 prostatic
      adenocarcinomas.
AB  - A series of 325 patients with prostatic adenocarcinoma followed-up for over 13
      years was subjected to histomorphometric analysis for the following prognostic
      factors: the Gleason score and 10 nuclear morphometric factors (mean nuclear
      area, nuclear perimeter, shortest and longest nuclear axis, form factor and their
      SDs), using the IBAS 1&2 image analyzer. Nuclear factors, Gleason score (P =
      0.0013-0.0148), and T-category (P = 0.004-0.0107) were significantly
      interrelated, while the M-category was independent of the morphometric
      parameters. Nuclear factors (P = 0.0003-0.5), Gleason score (P < 0.0001), T
      category (P < 0.0001) and M-category (P < 0.0001) predicted the disease outcome.
      In T1-2M0 tumors, the T-category (P = 0.0001), Gleason score (P < 0.0001), SD of
      nuclear area (P = 0.057), SD of nuclear perimetry (P = 0.039), mean shortest
      nuclear axis (P = 0.030), SD of the shortest nuclear axis (P = 0.0045), SD of the
      longest nuclear axis (P = 0.009), and nuclear form factor (P = 0.0123) were
      significant prognostic factors. In the multivariate survival analysis, the
      nuclear area had independent prognostic significance only in T1 tumors, whereas
      in other subcategories, the clinical stage, Gleason score, and patient age
      included all the available prognostic information. The results indicate that
      nuclear morphometric measurements are of borderline significance only in
      evaluating the intrinsic malignancy of prostatic adenocarcinoma.

PMID- 7638085
TI  - Purification of estramustine-binding protein and production of monoclonal
      antibodies to its different components.
AB  - Estramustine-binding protein (EMBP) is a heterodimeric 46-kDa glycoprotein that
      is secreted from the prostate. Upon reductive cleavage it decomposes into two
      closely related components, C1 and C2, and the shared glycosylated peptide C3.
      EMBP binds estramustine and estromustine, the active metabolites of estramustine
      phosphate (Estracyt), which is a drug with antimitotic properties used in the
      treatment of prostatic carcinoma. In the present study, a two-step procedure
      (i.e., anion-exchange and Con A-Sepharose chromatography) is described for the
      isolation of EMBP in high yield from rat prostate tissue. Mouse monoclonal
      antibodies (mAbs) were produced using the major DEAE-Sepharose fraction of EMBP
      as an immunogen. Eleven mAbs were selected by screening in a solid-phase ELISA.
      One displayed high-affinity binding with soluble EMBP (Ka approximately 3 x
      10(10) M-1) and crossreacted with a human prostate tumor extract in a
      radioimmunoassay. The epitopes defined by these mAbs were analyzed by Western
      immunoblotting. All constituents of EMBP, except component C1, were identified by
      at least one antibody. Nine visualized either one or both of the two EMBP
      subunits under denaturing conditions, two of which retained their reactivity
      after reduction of disulfide bridges. One epitope was exposed to its mAb only
      when the antigen was in its reduced state. The immunoreactivity was eliminated by
      protease treatment, whereas deglycosylation with glycopeptidase F had a minimal
      effect. EMBP has been detected in tissues other than the prostate as well as in
      prostate neoplastic specimens and in several other human malignancies. Hence,
      these mAbs will be a useful tool in the characterization of EMBP in different
      tissues and in evaluating existing and in defining new indications for Estracyt
      therapy.

PMID- 7638084
TI  - In vitro propagated dendritic cells from prostate cancer patients as a component
      of prostate cancer immunotherapy.
AB  - T cell-mediated cancer immunotherapy requires efficient antigen-presenting cells.
      Dendritic cells (DCs) are arguably the most efficient antigen-presenting cells
      studied to date. Individuals with prostate cancer often undergo various therapies
      which may compromise their immune system, including the state of their DC
      precursors. We report the in vitro propagation of DCs from peripheral blood of
      patients with prostate cancer, most of whom are in clinical stages D1 or D2 and
      have undergone radiation therapy. After 7 days in culture, the number of DCs
      recovered were 20-50-fold higher than those isolated directly from peripheral
      blood. This number is comparable to findings of previous studies with healthy
      individuals. Cultured patients' DCs were capable of presenting tetanus toxoid to
      autologous T cells in vitro. Furthermore, T cells from 2 of 4 patients
      proliferated when cultured with their DCs and the lysate of a human prostate
      cancer cell line (LNCaP), demonstrating the potential role of autologous DCs in
      prostate cancer immunotherapy studies.

PMID- 7638086
TI  - Rat prostatic inhibin: less than 35 kDa protein(s).
AB  - An attempt was made to purify and physicochemically characterize the inhibin-like
      activity of rat ventral prostate based on the technique of immunosorption. It was
      possible to partially purify prostatic inhibin by affinity chromatography and the
      molecular size of inhibin-like material was shown to be less than 35 kDa.

PMID- 7638087
TI  - Association of some hydrolytic enzymes with the prostasome membrane and their
      differential responses to detergent and PIPLC treatment.
AB  - Prostasomes are human prostate derived organelles that were isolated from both
      prostatic fluid and seminal plasma for the present study. Specific activities
      were determined for prostasome membrane-associated enzymes, alkaline phosphatase
      (ALP), 5'-nucleotidase (5'NT), and alkaline phosphodiesterase I (APD). The mode
      of their membranous anchoring was studied by treatment of prostasomes with
      phosphoinositol-specific phospholipase C (PIPLC) and different detergents. A
      substantial amount of ALP (50%) and 5'NT (31%) was released by incubation of
      prostasomes with 2 U/ml of PIPLC contrary to the small amount of APD (12%)
      released by the same treatment. After PIPLC treatment, the enzymes were recovered
      in the aqueous phase after phase repartition in Triton X-114 indicating that
      PIPLC removed the hydrophobic domain converting the enzymes from membrane-linked
      to aqueous soluble forms. Octyl glycoside was the most efficient one among
      different detergents to solubilize the enzymes from the prostasome membrane. Both
      ALP and 5'NT were resistant to the treatment with Triton X-100 and Triton X-114.
      These results suggest that ALP, 5'NT, and APD are more or less extensively linked
      to the prostasome membrane via a glycophosphoinositide anchor.

PMID- 7638088
TI  - [Diagnostic methods for HIV infections].

PMID- 7638089
TI  - [Immunologic processes in the human placenta and their role in antiviral
      resistance. II. Specific immunity].
AB  - This study presents news about mechanisms of antibody responses and cell-mediated
      immunity in the human placenta. The cytokines such as TNFs, ILs, CSFs, produced
      by the placental cells, may play a role in protection against viral pathogens.
      The immunological function at the materno/fetal interface probably is associated
      with a phase of embryonic development.

PMID- 7638090
TI  - [Biological properties of interleukin 10].
AB  - Interleukin-10 (IL-10) is produced predominantly by T-helper lymphocytes and
      macrophages. IL-10 inhibits lymphocyte-induced cytokine production (CSIF-
      cytokine synthesis inhibitory factor), cooperates in B lymphocytes activation as
      well as macrophages--monocytes deactivation (MDF--macrophage deactivating
      factor). Due to its immunosuppressive properties IL-10 may be used in therapy of
      some T-cell induced diseases.

PMID- 7638091
TI  - [Katacalcin--structure, secretion and clinical significance].

PMID- 7638092
TI  - [Enkephalinase (EC. 3.4.24.11) -- characteristics, distribution and role in the
      human].
AB  - Enkephalinase, the enzyme originally purified from kidney, is largely represented
      in brain and other tissues, namely in the airways, blood cells, kidney and the
      gastrointestinal tract. The highest enkephalinase activity was observed in
      duodenum and jejunum. Beside the participation in hydrolysis of proteins,
      enkephalinase degrades many biologically active peptides in the tissues and on
      that way can regulate some secretory or motoric functions.

PMID- 7638093
TI  - [Endothelin (ET) in kidneys].
AB  - Peptides from endothelin family (ET-1, ET-2, ET-3), synthesized by the
      endothelial cells, are now known to exert diverse biological effects on wide
      variety of cell types and tissues mainly through two subtypes of receptors (A-
      and B-type ET receptors). Tissue distribution and mechanism of action of ET
      peptides and their receptors are reviewed. The biological role of ET peptides and
      receptors in health as well as in renal disease is discussed.

PMID- 7638094
TI  - [Biochemical aspects of free radical mediated tissue injury].
AB  - A radical is any molecule that contains one or more unpaired electrons. Radicals
      are normally generated in many metabolic pathways. Some of these radicals can
      exist in a free form and subsequently interact with various tissue components
      resulting in dysfunction. The potential role of oxygen- and xenobiotic-derived
      free radical in the pathology of several human diseases has stimulated extensive
      research linking the toxicity of numerous xenobiotics and disease processes to a
      free radical mechanism.

PMID- 7638095
TI  - [Activity of antioxidant enzymes in cancer diseases].
AB  - In this work comprehensive data of antioxidant enzymes are reviewed and their
      role in carcinogenesis is discussed. When compared to their normal tissue
      counterparts, more of the tumor tissues were low in Cu, Zn-SOD and catalase
      activity and in some cases in Mn-SOD. It is probably characteristic for tumor
      tissues. Glutathione peroxidase, and glutathione reductase and glucose-6
      phosphate dehydrogenase activities are highly variable. The reason why cancerous
      cells exhibit abnormal levels and activities of antioxidant enzymes is unknown.
      It was hypothesized, that during formation of the tumor, by certain obscure
      mechanism, cells with imbalance of antioxidant enzymes profile were selected over
      normal cells. It is not known whether the changes in antioxidant defence observed
      in cancerous tissues play a role in carcinogenesis, or are formed as a results of
      the disease.

PMID- 7638096
TI  - [Induced modifications of liver cytochrome P-450 levels as a function of age in
      rats].
AB  - In this paper we showed age effect on hepatic level of cytochrome P-450. We
      discussed effects of inductors on this hemoprotein also. Cytochrome P-450 content
      increased to 1-month of life, but decreased to 4-month. In the oldest rats
      cytochrome P-450 increased again. Content of this hemoprotein was induced by
      phenobarbital and beta-naphthoflavone in all examined groups, especially strong
      in young animals. Induction effect of dexamethasone was observed in 4-20-month of
      life.

PMID- 7638097
TI  - [The role of selenium during pregnancy and in the newborn infant].
AB  - The paper describes the up-to-date knowledge on the essential trace element,
      selenium, in human nutrition, its concentration in blood during pregnancy and in
      milk during lactation. Changes in selenium concentration in maternal milk during
      various stages of lactation and selenium concentration in infant blood as well as
      the selenium intake by breast- and formula-fed infants is discussed.

PMID- 7638098
TI  - [Human luteinizing hormone (hLH)].
AB  - Heterodimeric composition and amino acid sequence of hLH is reviewed. The hormone
      isoforms and methods of their assay are summarized. Releasing of the hormone, its
      control by synthetic antagonists and agonists and their significance for therapy
      are described. Structure and function of hLH receptor are presented.

PMID- 7638099
TI  - [Botulinum toxin: structure, mode of action and therapeutic use].
AB  - Structure, biological activity, mode and mechanism of action of botulinum toxin
      as well as its therapeutic use is described. Botulinum toxin type A, one of the
      most potent biologic toxins, has been found to be of therapeutic value in the
      treatment of several neurologic and ophthalmologic diseases. Its ability to
      produce chemical denervation of muscles makes it option for treatment of
      disorders in which traditional therapeutic procedures are of limited value (e.g.
      blepharospasm and other focal dystonias, strabismus, spasticity).

PMID- 7638100
TI  - [Feto-maternal immunoregulation].
AB  - One of the great mysteries in modern immunology is how extraembryonic membranes
      escape rejection by maternal immune response, although they express paternal
      genes/anti-genes which should stimulate allogenic recognition and rejection.
      Generally, two theories try to explain the pregnancy phenomenon. One of the
      emphasizes the role of immunosuppressive reactions in the protection of the
      fetus. On the contrary, the "immunotropism" theory insists on the importance of
      mother's immune response to paternal antigens of the conceptus. Moreover, the
      last years abound in discoveries on molecules regulating cell-cell interactions
      at the level of the initiation and effector stage of the immune response. The
      best examples of such molecules could be extracellular matrix proteins,
      integrins, interleukins and various growth factors. The discussion on those
      molecules as regards their role in the protection of the fetus was the main aim
      of this article.

PMID- 7638101
TI  - [Biology of interleukin 6 (IL-6) and its significance in the pathogenesis of some
      diseases].
AB  - In the paper numerous activities of IL-6 toward various normal and neoplastic
      cells are reviewed. The role of this cytokine in pathophysiology of a various
      disease including infections and inflammatory and autoimmune diseases as well as
      in leukaemias, lymphomas and other neoplastic diseases is presented. Potential
      clinical value of the IL-6 levels in the serum and the role of its recombinant
      form in the treatment of thrombocytopenia and some neoplastic diseases is also
      discussed.

PMID- 7638102
TI  - [Flavonoids in medicine].
AB  - Flavonoids are a broadly distributed class of naturally occurring plant products.
      Because of their widespread occurrence in edible plants such as fruits,
      vegetables and grains, they are an integral part of the human diet. Several
      problems concerning various biological actions of the flavonoids have been
      presented.

PMID- 7638103
TI  - [Antibodies against neutrophil cytoplasm and their role in pathology and
      diagnosis of systemic vasculitis].
AB  - Experimental data and clinical observations suggesting the role of antibodies
      against neutrophil cytoplasm in pathology and diagnosis of systemic vasculitides
      have been presented. There are no data indicating that ANCA specificity allow to
      distinguish diverse forms of necrotizing vasculitis. However, detection of ANCA
      has a diagnostic interest since it is a key to the diagnosis of vasculitis in
      complex clinical settings where diagnosis is not obvious. ANCA may be useful in
      monitoring the course of the disease and effects of treatment.

PMID- 7638104
TI  - [Non-atrial natriuretic peptides].
AB  - This paper described newly discovered peptides, brain natriuretic peptide and C
      type natriuretic peptide. Their structure and metabolism as well as peptides
      participation to many physiological and pathological states have been reviewed
      with a special emphasis to their role in blood pressure regulation and mineral
      and fluid balance.

PMID- 7638105
TI  - [Induced modification of liver NADPH-cytochrome P-450 activity and II microsomal
      electron transport chain as a function of age in rats].
AB  - In this paper we showed age effect on NADPH-cytochrome P-450 reductase activity,
      cytochrome b5 and NADH-cytochrome b5 reductase from rat liver. We discussed
      effect of some I, II and III classes inductor also. Activity NADPH-cytochrome P
      450 reductase softly decreased from 0.5-2-month of life, but in older groups
      gradually increased. In 28-month-old rats it was twice fold youngest.
      Phenobarbital and dexamethasone (without 28-month-old age rats) induced but beta
      naphthoflavone inhibited activity of this reductase. Cytochrome b5 content softly
      decreased to 4-month of life. In older animals changed of this hemoprotein
      content were not observed. The examined inductors of monooxygenase system
      decreased cytochrome b5 level. NADH-cytochrome b5 reductase activity increased to
      1-month of life, but in older group decreased. After 2-month changes of activity
      were very small only. Phenobarbital, beta-naphthoflavone and dexamethasone
      inhibited activity of this reductase.

PMID- 7638106
TI  - Localization of transforming growth factor beta and its natural inhibitor decorin
      in the human placenta and decidua throughout gestation.
AB  - Transforming growth factor beta (TGF beta) produced at the human fetomaternal
      interface has been shown to play a crucial role in controlling trophoblast
      invasion of the uterus. Decorin, a naturally occurring chondroitin-dermatan
      sulphate proteoglycan which binds TGF beta can inhibit its activity. In this
      study, immunohistochemical techniques were used to determine the locations of TGF
      beta and decorin within the human placenta and decidua throughout normal
      gestation. In addition, sites of TGF beta 1 mRNA synthesis were identified in
      early and late placenta by in situ hybridization. Results revealed the presence
      of immunoreactive TGF beta in the cytoplasm of villous syncytiotrophoblast and
      extravillous trophoblast cells throughout gestation. TGF beta immunostaining was
      absent from villous cytotrophoblast at all gestational ages examined. The
      extracellular matrix (ECM) of the villous core at all stages of gestation and
      cells of the cytotrophoblastic shell of the term placenta were immunoreactive for
      TGF beta. Within decidual tissue, TGF beta was primarily localized in the ECM
      during the first trimester and only a small proportion of decidual cells
      exhibited intracellular labelling. At later gestational ages the majority of
      decidual cells showed intracellular labelling accompanied by a decrease in ECM
      staining. This switch may reflect increased TGF beta synthesis by the decidual
      cells, decreased release, or altered TGF beta binding to one or more ECM
      proteins. In situ hybridization indicated that TGF beta 1 mRNA was primarily
      localized to the syncytiotrophoblast cell layer with low intensity signals
      present in extravillous trophoblast cells, in trophoblast cell columns, and in
      large decidual cells. At term, TGF beta 1 mRNA was located in both the
      syncytiotrophoblast and villous mesenchymal cells. Decorin was immunolocalized to
      the ECM of the mesenchymal core of the chorionic villi throughout gestation and
      no immunoreactivity was observed in either villous or extravillous trophoblast.
      In the first trimester decidua, decorin was localized to the ECM whereas decidual
      cells, decidual leucocytes, and the uterine epithelium were negative. At later
      gestational ages, the ECM as well as a few decidual cells displayed weak
      immunoreactivity. A strong co-localization of TGF beta and decorin in the ECM of
      first trimester decidual tissue suggests that decorin may aid TGF beta storage or
      limit its activity in the ECM.

PMID- 7638107
TI  - Identification and isolation of corticotrophin-releasing hormone-positive cells
      from the human placenta.
AB  - During human pregnancy, plasma corticotrophin-releasing hormone (CRH) levels rise
      from undetectable amounts prior to 20 weeks gestation to reach a peak near term,
      with an exponential rise during the final 5 weeks of gestation. Within hours of
      parturition plasma levels fall and rapidly return to undetectable baseline
      measurements. The appearance of CRH in maternal plasma has been attributed to the
      placental production and subsequent release into the maternal circulation of this
      hormone. Previous studies have shown that human placental extracts contain a CRH
      like peptide and this has been reinforced by the observation of CRH mRNA in
      placental tissue. Initial attempts to identify the site of production using
      immunocytochemistry have led to conflicting results. This study attempts to
      clarify this situation by using a variety of highly specific anti-CRH antibodies
      to show the cellular expression of placental CRH. Intense CRH staining was
      observed in the syncytial trophoblast layer in first trimester and term chorionic
      villi, whilst the underlying cytotrophoblast appeared to be negative. The fetal
      membranes also contained CRH immunoreactivity with the cytotrophoblast cells in
      the chorionic membrane displaying the most intense staining. CRH immunoactivity
      was also observed in the amnion and in some cells in the decidua. As a model of
      cellular CRH expression, cytotrophoblast cells from term chorionic membrane were
      isolated and shown to be positive for CRH.

PMID- 7638108
TI  - Expression of desmin and vimentin intermediate filaments in human decidual cells
      during first trimester pregnancy.
AB  - Human endometrial stromal cells (decidual cells) display dramatic alterations in
      cell shape and size during decidualization. The present study was designed to
      demonstrate the expression of two major cytoskeletal elements, desmin and
      vimentin, in human pregnant endometrial decidual cells. Additionally, stage
      dependent variations of those intermediate filaments (IFs) among gestational
      weeks were also evaluated with regard to the support and maintenance of
      decidualization. Materials were obtained from legal suction terminations of
      pregnancies of 3-10 weeks gestation. Tissue specimens were either blocked in
      paraffin or enzymatically dissociated for isolation of decidual cells which
      subsequently were cultured as monolayers. Immunoperoxidase and immunofluorescence
      staining methods were applied by using anti-desmin and anti-vimentin monoclonal
      antibodies. Both desmin and vimentin expression were observed during the early
      weeks of pregnancy (3-6 weeks). These two types of IFs were also detected in
      short-term cultures in a filamentous fashion either within the cell body or at
      cellular attachment plaques. When decidual cells were cultured for longer periods
      (40-60 days), the expression of desmin dramatically declined while vimentin
      expression was maintained in a rather diffuse and more abundant fashion. The in
      situ expression of desmin and vimentin in later weeks of gestation (7-10 weeks)
      correlated with immunofluorescence staining of long-term cultured cells in that
      desmin staining was very weak and mostly undetectable where vimentin expression
      persisted and was evenly distributed throughout the entire stroma. The results
      demonstrate the differential expression of two major IFs, desmin and vimentin, in
      human endometrial stromal cells during decidualization and subsequent
      placentation. The persistence of vimentin in all stages examined suggests that
      this IF is probably involved in cell morphology and nucleocytoplasmic integrity.
      The temporal pattern of desmin expression suggests a role for this IF during the
      rapid onset of the decidualization process.

PMID- 7638109
TI  - Nitric oxide and human umbilical vessels: pharmacological and immunohistochemical
      studies.
AB  - Human umbilical vessels are devoid of nerves and therefore endothelial cells may
      play an important role in the control of fetoplacental blood flow. In this study
      we examined the pharmacological effects of various substances, known to produce
      endothelial-mediated vasodilation in many blood vessels, on the human umbilical
      artery and vein from legal terminations [mean gestational age, 15 (8-17) weeks; n
      = 12] and normal term vaginal deliveries [mean gestational age, 39 (38-41) weeks;
      n = 12]. Acetylcholine, adenosine 5'-triphosphate, the calcium ionophore A23187
      and substance P had no effect on raised vascular tone, whereas sodium
      nitroprusside relaxed 5-hydroxytryptamine (5-HT) preconstricted, umbilical artery
      and vein from both early and late pregnancy. L-NG-Nitroarginine methyl ester (L
      NAME) had no effect on basal tone or on high tone, after it was raised by 5-HT.
      Localization of nitric oxide synthase [NOS, type I (neuronal)] was examined in
      the same umbilical vessels using electron immunocytochemistry. No NOS
      immunoreactive endothelial cells were observed in the umbilical vessels taken
      during early pregnancy. However, the percentage of NOS-immunoreactive endothelial
      cells in umbilical artery and vein from late pregnancy was 3 and 10 per cent,
      respectively. These results suggest that nitric oxide contributes little, if any,
      to the local control of umbilical blood flow throughout pregnancy, despite the
      presence of NOS-immunoreactivity in a subpopulation of endothelial cells in late
      pregnancy.

PMID- 7638110
TI  - Volume-activated amino acid efflux from term human placental tissue: stimulation
      of efflux via a pathway sensitive to anion transport inhibitors.
AB  - The effect of a hyposmotic challenge and hence cell-swelling upon the efflux of a
      variety of solutes from isolated human placental tissue has been examined. A
      hyposmotic shock increased the fractional release of taurine, the most abundant
      free amino acid in placental tissue, via a pathway sensitive to niflumic acid,
      DIDS (4,4'-Diisothiocyanatostilbene-2',2'-disulphonic acid,) NPPB (5-Nitro-2(3
      phenylpropylamino)benzoic acid) and DIOA (R(+)[2-n-butyl-6,7-dichloro-2
      cyclopentyl-2,3-dihydro-1-oxo-1H-inden -5-y) oxy] acetic acid). In contrast,
      tamoxifen was without effect. The cell-swelling induced efflux of taurine was
      attenuated (40 per cent) by replacing external Cl- with NO3-. The efflux of
      glutamic acid was also markedly increased by a hyposmotic challenge. Niflumic
      acid inhibited both basal and volume-activated glutamic acid efflux. A hyposmotic
      shock also increased alpha-aminoisobutyric acid efflux but not that of 3-O
      methylglucose and SO4(2)-. The results suggest that the human placenta can
      respond to cell-swelling by releasing organic osmolytes such as amino acids via a
      pathway which is sensitive to anion transport inhibitors. However, it appears
      that the volume-activated amino acid transport system is independent from the
      placental anion-exchange pathways. The efflux of these compounds may act with K+
      and Cl- efflux to effect a regulatory volume decrease in placental tissue. In
      addition, volume-activated transport may play a role in transplacental amino acid
      transfer.

PMID- 7638111
TI  - Immunohistochemical localization of pregnancy-related placental protein 4 in
      human placenta, umbilical cord and adult human female genital tissues.
AB  - Placental protein 4 (PP4) is a soluble placental tissue protein which was
      isolated from human placenta. The aim of the present study was to demonstrate the
      localization of cells containing PP4 in human placenta and in various female
      genital tissues under normal conditions. PP4 immunoreactive structures were
      demonstrated by using the peroxidase-antiperoxidase immunohistochemical
      technique. The samples were obtained from normal human placenta, umbilical cord,
      uterine cervix, endometrium, ovary and vulva. The most differentiated
      trophoblastic cells, the syncytiotrophoblasts, as well as the intermediate
      trophoblast cells contained PP4. PP4 immunoreactivity was present in umbilical
      cord as well. Occasionally PP4 was detected in normal ovarian, endometrial or
      vulvar tissue samples. Cervix and myometrium were free of PP4 immunoreactive
      material. PP4 staining was cytoplasmic. Our findings indicate that PP4 cannot be
      considered specific for the placenta since it is present in some human adult
      tissues as well.

PMID- 7638112
TI  - Conference report: fetal origins of adult disease--report of the First
      International Study Group, Sydney, 29-30 October 1994.
AB  - The epidemiological observations that prenatal and perinatal events lead to adult
      disease are now well supported by animal data. The events in the periconceptual
      period, in early and late pregnancy and in infancy can effect programming of
      cardiovascular, endocrine and metabolic regulatory systems. However, the
      mechanisms underlying these pathological changes remain to be elucidated. Until
      this is addressed in experimental animals, clinical trials in human pregnancy are
      premature.

PMID- 7638113
TI  - [Can the prognosis of early rheumatoid arthritis be predicted?].
AB  - Rheumatoid arthritis is a frequently and potentially severe disease which causes
      a functional handicap in nearly half the patients 10 years after the
      identification of the first clinical manifestations. Some patients develop very
      severe forms with joint destruction and multiple organ involvement while in
      others the disease remains benign, even after a long clinical course of several
      years. Theoretically, the future intensity of rheumatoid arthritis in a given
      patient cannot be predicted at the time of early diagnosis. No prognosis factor
      has been identified and universally accepted and validated. A marker of prognosis
      would be highly appreciated by clinicians who could then more closely adapt their
      management decisions to the disease potential. Clinical and biological data
      collected to date have provided a limited amount of prognostic information but
      recent progress in molecular biology suggests that genetic markers could be
      correlated with disease severity. Several HLA-DRB1 alleles including DR1*0401,
      DRB1*0404, DRB1*0101 and sometimes DRB1/1001 and DRB1/1402 are potential markers.
      In France 85% of the patients with rheumatoid arthritis have one of these genes
      compared with 25% in the general population. In patients with a "high risk"
      alleles, the second haplotype could also have prognostic value. It would appear
      possible to distinguish immunogenetically homogeneous subpopulations
      corresponding to the more severe forms of the disease. It is still too early to
      propose therapeutic strategies based on current prognosis markers, but a
      combination of the most pertinent markers should be already used to select
      homogeneous subsets of patients in fundamental research and clinical trials.

PMID- 7638114
TI  - [Branchio-oto-renal syndrome. 4 cases in three families].
AB  - Branchio-oto-renal syndrome is an inborn disease of autosomal dominant
      transmission and variable expression. The syndrome associates ear pits, branchial
      cleft fistulas or cysts, deafness and renal anomalies heavily compromising
      prognosis. We report four adults (2 males, 2 females) in three different families
      with branchio-oto-renal syndrome. All 4 probands were seen for renal failure,
      with hematuria in 2 and proteinuria in the 2 others. Among the 62 family members
      examined 19 had at least one sign of branchio-oto-renal syndrome. Four
      pregnancies were followed during the course of the study, only one reached term.
      The frequency of branchio-oto-renal syndrome is probably underestimated.
      Prevalence has been estimated at 1/40,000 births. It accounts for 2% of the cases
      of severe deafness in children. Neck and ear morphology should therefore be
      carefully examined in patients with renal or urinary tract dysplasia. Women with
      a mild form of the disease with moderate renal failure may give birth to an
      infant with very severe renal failure leading to death either in infancy or in
      utero due to severe renal agenesia or hypoplasia.

PMID- 7638115
TI  - [Adrenalectomy under celioscopy. Experience of 25 operations].
AB  - OBJECTIVES: Determine the indications for laparoscopic adrenalectomy on the basis
      of our experience. METHODS: We performed 25 laparoscopic adrenalectomies for
      primary hyperaldosteronism (n = 10), non-ACTH-dependent hypercortisolism (n = 6),
      Cushing's disease (n = 2 including one bilateral operation), pheochromocytoma (n
      = 1) and tumoral formation (n = 5). RESULTS: The operation required conversion to
      an open procedure in 4 cases (16%). The post-operative period was uneventful in
      19 and was clearly less painful. Improved delay to normal intestinal function and
      rapid return to normal activities was also beneficial in these patients with no
      parietal damage. Complications occurred in two cases: one local asymptomatic
      collection and one localized pancreatitis requiring surgical drainage of an
      abscess. COMMENTS: Compared with our experience with open procedures, the
      inconvenience of a long laparoscopic procedure (2h 45 min for unilateral
      adrenalectomy), is counterbalanced by the reduction in risk to complications in
      64% of the cases due to the simplicity and lack of parietal damage. We currently
      propose the laparoscopic procedure for tumours under 6 cm in diameter and for
      certain pheochromocytomas and rely on the open procedure for proven or suspected
      corticoadrenalomas.

PMID- 7638116
TI  - [Cognitive psychotherapy for depression in adolescents: a new therapeutic
      perspective].
AB  - The nosological concept of depression in adolescents is still relatively poorly
      understood. Clinical expression varies greatly although behavioural disorders and
      suicidal acts are frequent signs. As an alternative to drug therapy, cognitive
      psychotherapy appears to be a promising approach offering a structured
      therapeutic tool applicable within a short period of time. We report the case of
      a 18-year-old girl who suffered from chronic depression and had attempted suicide
      several times in spite of previous hospitalization and psychoanalytic therapy.
      She was successfully treated with 16 sessions of cognitive psychotherapy
      conducted according to the Beck method in combination with fluvoxamine which had
      been insufficient given alone. The different phases of the therapeutic approach
      are discussed during hospitalization then as an out patient. Cognitive
      psychotherapy is technically feasible treatment for depression in the adolescent
      and has been demonstrated to be effective in our case.

PMID- 7638117
TI  - [Neurologic accident of decompression: a new indication of transesophageal
      echocardiography].
AB  - Decompression sickness in a 33-year-old SCUBA diver led to neurological lesions
      with brain damage. The existence of a patent foramen ovale detected with a
      transoesophageal contrast echocardiography suggested paradoxal gas embolism. This
      observation emphasizes the intest of transoesophageal contrast echocardiography
      in decompression sickness as discussed in the literature. Its widely utilization
      would permit a better understanding of the pathophysiology of decompression
      sickness. It also may help the physician in deciding whether or not to authorize
      further diving.

PMID- 7638118
TI  - [Rheumatoid arthritis: its relationship with HLA DR molecules].
AB  - Over the last two decades, much progress has been made in our understanding of
      the genetics of rheumatoid arthritis since the discovery of a link between the
      HLA DR4 antigen and rheumatoid arthritis in 1974. In molecular biology, the
      precise alleles of the HLA DRB1 gene which encode for different specific
      molecules have been identified. They have been used to link rheumatoid arthritis
      to certain HLA DRB1 subtypes recognized as "high risk" alleles. It has been
      hypothesized that the shared epitope would be one way for a molecular approach to
      susceptibility of allelic variants in rheumatoid arthritis. More recently, the
      notion that high risk DRB1 alleles might contribute to disease severity has also
      been put forward. HLA DRB1 alleles carrying a risk of rheumatoid arthritis would
      have two properties: they could serve as a marker of the risk of developing the
      disease and of disease severity both essential elements for the clinician.

PMID- 7638119
TI  - [Liver transplantation for alcoholic liver disease. Selective indications].
AB  - Alcoholic liver disease represents about 15% of all indications for liver
      transplantation. Patient selection is difficult, and must be rigorous. Peri
      operative risks are evaluated on the same basis as for other chronic liver
      diseases, with special attention for alcoholic extra-hepatic morbidity and
      nutritional status. Definite withdrawal from alcohol is mandatory. Predictive
      factors of long-term abstinence are the absence of psychopathologic state, an
      adequate social and affective situation, the possibilities of professional
      reinsertion, and a strong motivation of the patient towards liver
      transplantation. A six-month period of complete abstinence before registration on
      a liver transplantation waiting list is not mandatory, although intermittent
      alcoholic abuse before transplantation should be an exclusion factor. Liver
      transplantation must be proposed based on the severity of liver failure, as
      assessed by pronostic scores. It must be rapidly discussed following an acute
      episode of decompensation, in the absence of a significant improvement despite
      adequate medical therapy. It must also be discussed for long-term abstinent
      patients, with an apparently stabilized cirrhosis, but with an important decrease
      of the functional liver mass. The evaluation of the functional liver mass is
      based upon the Child-Pugh score, associated with the results of metabolic liver
      function tests, the measurement of the hepatic volume and the severity of portal
      hypertension.

PMID- 7638121
TI  - [Presence of G1691A mutation on the gene of factor V in arterial thrombosis].

PMID- 7638120
TI  - [Polycystic ovarian dystrophies. Diagnostic criteria and treatment].
AB  - Polycystic ovary syndrome (PCOS) is an association of oligomenorrhoea,
      anovulation, hyperandrogenism, obesity and enlarged polycystic ovaries. It
      provides a model of loss of cyclic ovarian function. It is classical to
      distinguish between type I and type II PCOS. In type I, the primary mechanism
      seems to be hypothalamic dysfunction, which causes an increase in the frequency
      and amplitude of LH pulses, with diminished FSH release. LH hypersecretion
      stimulates ovarian stroma hyperplasia while FSH insufficiency results in the
      failure of folliculare maturation and hence anovulation. Aromatization of
      androgens to oestrogens is responsible for permanent oestrogen overproduction,
      which favours LH hypersecretion. Type II PCOS is more frequent and may have
      multiple causes (local, endocrine, systemic, iatrogenic) that interfere with the
      gonadotropic axis and alter the FSH/LH ratio. The most efficient treatment of
      hirsutism is cyproterone acetate which alone has both antiandrogenic and
      antigonadotropic properties. Clomifene citrate remains the "first choice"
      treatment of infertility associated with anovulation.

PMID- 7638122
TI  - [Primary T lymphoma of the bladder in a HIV infected patient].

PMID- 7638123
TI  - [Mode of failure of transfusion. Systematic analysis of dysfunctions during 4
      months].

PMID- 7638124
TI  - [Paralysis of the recurrent and phrenic nerves after Mycoplasma pneumoniae
      infection].

PMID- 7638126
TI  - [Skin, a privileged target for gene therapy].
AB  - Keratinocytes, fibroblasts and tumour cells of skin cancers can be the target of
      two different strategies based on gene therapy: direct in vivo gene transfer or
      in vitro transfer after harvesting skin cells. For in vivo transfer, the problem
      is to develop techniques which limit effective gene transfer to skin cells
      without dissemination. For in vitro transfer, the keratinocytes, for example, are
      isolated and cultured to produce an epithelium comparable to the body surface
      which is then grafted as has been done for burns for more than a decade.
      Fibroblasts can also be biopsied and cultured. Transfer systems include use of
      viral vectors including retroviruses and adenoviruses and inert physicochemical
      methods currently under development. Theoretically, gene therapy could be used
      for genodermatoses, expression of local or systemic therapeutic factors and gene
      transduced tumour cells for skin cancer. The most rapid developments for gene
      therapy for the skin will probably be the use of keratinocytes and fibroblasts
      for the production of local or systemic proteins with a therapeutic effect.

PMID- 7638125
TI  - [Thrombotic microangiopathy of tumoral origin: value of early combination
      chemotherapy and plasma exchange].

PMID- 7638127
TI  - [Vagal syncope in young adults: specificity of the tilt-table test].
AB  - OBJECTIVE: The head-up tilt test has been used for more than 10 years to
      reproduce vagal lipothymia. The criteria for a positive test and specificity are
      however still lacking. METHOD: Thirty male volunteers, age 18 to 35 years, with
      no past history of lipothymia nor any signs of hypervagotonicity at physical
      examination, on fasting blood samples or on exercise tests with sudden
      interruption and Holter recording were selected for the study. Two head-up tilt
      tests at 60 degrees for 45 minutes were conducted, one with no presensitivisation
      and the other with a bolus of isoproterenol (2, 4, 6 and 8 micrograms) starting
      30 minutes after the beginning of the test. Blood pressure was measured
      throughout the test. RESULTS: The systolic blood pressure curves showed drops of
      more than 30 mmHg accompanied by spontaneously resolving clinical signs in 6 of
      the 30 subjects during the non-sensitized tests and in 14 out of 30 during the
      sensitized tests. A symptomatic drop in systolic blood pressure of more than 30
      mmHg compared to the moment before the malaise accompanied by clinical signs
      which did not resolve within 1 minute and required returning to the supine
      position occurred in one volunteer during a non-sensibilized test. This same type
      of reaction was observed in 4 volunteers during sensitized tests, three times
      after an isoproterenol bolus. CONCLUSION: Taking this later manifestation as the
      criteria for a positive head-up tilt test, the specificity of the non-sensitized
      and isoproterenol-sensitized tests in the young adult are 96.7 and 86.7%
      respectively. These findings must be considered with caution since there is no
      proof that these young men with no past history of hypervagotonicity but a
      positive head-up tilt test may be one day confronted with a situation generating
      a vagal reaction.

PMID- 7638128
TI  - [Evaluation of the ventilatory function in elderly subjects].
AB  - OBJECTIVES: Many elderly subjects are at risk of respiratory failure due to
      effect of age on ventilatory system and the deleterious effects of toxins and
      respiratory diseases. As spirometry is the main technique currently used to
      detect altered ventilatory function we first used this method in very elderly
      subjects then compared the results with clinical measurements of chest and
      abdominal ampliation. METHODS: Among 65 subjects over 75 years of age, with no
      cardiorespiratory or neuropsychologic impairment and who had undergone spirometry
      and chest and abdominal ampliation measurements in 1991, 24 were re-examined in
      1994 using exactly the same techniques. Forced vital capacity and maximum
      expiratory volume/second were measured at the patient's home with a previously
      calibrated spirometer. All tests were run according to the recommendations of the
      European Respiratory Society. Variations in upper chest, lower chest and
      abdominal circumferences were also recorded. RESULTS: Mean age of the subjects
      was 84.1 +/- 3.7 years and all spirometric tests were reproductible within a
      given measurement session. There was no significant difference for forced vital
      capacity or for maximum expiratory volume/second between the 1991 and the 1994
      values with variations of 2.1 +/- 0.4 and 9.4 +/- 3.4% respectively. Four of the
      24 initially asymptomatic subjects had signs of obstruction which resolved in 2
      with the salbutamol and/or ipratropium bromide. The correlations between
      spirometric data and chest and abdominal ampliations were significative.
      CONCLUSIONS: Spirometry can be an effective tool in elderly patients. In addition
      to frequent discovery of reversible bronchial obstruction (7 to 41% according to
      the series), it can be used to screen for reduced ventilatory "reserve". Chest
      ampliations measures also appear to be simple means of determining which subjects
      could benefit from physical therapy aimed at improving chest and abdominal
      musculature.

PMID- 7638129
TI  - [Treatment of metastatic malignant insulinomas. 2 cases].
AB  - Malignant insulinomas are slow growing tumours for which the prognosis is
      worsened by metastatic disease and sequellae of excess hormone secretion.
      Management of unresectable tumours includes intravenous chemotherapy and local
      treatments such as palliative surgery and transcatheter arterial embolization of
      liver metastases. Long-term survival can also be improved by inhibition of
      secretory products of the tumour with either octreotide, a somatostatin analogue,
      or diazoxide. We report two cases of malignant insulinomas with liver metastases
      for which objective responses were obtained with combination of local treatment
      and intravenous chemotherapy.

PMID- 7638130
TI  - [Symptomatic relief of carcinoid syndrome by ketanserin. A case].
AB  - The carcinoid syndrome is a rare clinical entity mainly characterized by flushing
      and diarrhoea. It is due to different biological mediators produced by tumours
      that arise from enterochromaffin cells. Such tumours are typically located in the
      ileum, have a long course and become symptomatic only in the presence of overt
      liver metastases. Among the involved mediators, the role of serotonin (5
      hydroxytryptamine, 5-HT) has been ascertained in the pathogenesis of diarrhoea,
      while it remains controversial in that of flushing. Ketanserin is a 5HT-2
      antagonist with no mixed receptor agonist-antagonist activity. We report the case
      of a severely distressing carcinoid syndrome fully dominated by ketanserin. The
      patient was a 75-year-old man, who came to our attention because of marked weight
      loss, impossibility to feed and almost continuous diarrhoea due to liver
      colonization of a mid ileum carcinoid tumour, previously resected at the age of
      65. Sustained facial and trunk flushing also presented several times daily.
      Ketanserin, 20 mg twice a day orally, was administered and then increased up to
      40 mg daily with no side effects and progressive complete control of both
      diarrhoea and flushing. It is suggested that ketanserin, due to its availability
      and tolerability, should first be considered for palliative relief of carcinoid
      syndrome. The literature on this subject is extensively reviewed.

PMID- 7638131
TI  - [Stenosis caused by mechanical colorectal anastomosis. Technique of plasty].
AB  - Stenosis occurs in 1.2 to 4% of the cases after colorectal anastomosis,
      especially after stapling. Ischaemia may have been favoured in our two cases.
      Treatment requires endoscopic dilatation or section of a sclerous diaphragm and
      may entail reconstruction of the anastomosis. The Kraske plasty is a simple and
      rapid procedure (case n. degree 1) and can be performed via endoluminal access
      (case n. degree 2) using a linear suture.

PMID- 7638132
TI  - [Use of anticoagulants during pregnancy].
AB  - Prolonged anticoagulant therapy may be indicated during pregnancy in patients
      with inborn diseases affecting haemostasis, mechanical heart valves, etc. A
      management scheme aimed at protecting both the mother and the foetus is presented
      on the basis of pharmacological data, the main series reported in the literature
      and the experience acquired at the Boucicaut hospital in Paris. Heparin should be
      used during the first trimester of pregnancy to avoid the teratogenic potential
      of antivitamin K drugs and to reduce the incidence of spontaneous abortions which
      increases in patients given oral anticoagulants. During the second and third
      trimester, antivitamin K drugs can be used more easily than heparin with no
      substantial increase in risk for the foetus. At delivery and during the immediate
      post partum period it is imperative to use a compound which does not cross the
      placental barrier (in order to avoid foetal hypocoagulation) and which has a
      short half-life. Heparin is therefore indicated again starting at eight months
      gestation. It is emphasized that despite careful management and follow-up by the
      co-ordinated efforts of cardiologists, obstetricians and the intensive care team
      haemorrhage occurs in 17% of the pregnant women given anticoagulants,
      particularly during the peri partum period.

PMID- 7638133
TI  - [Substitutive hormonal treatment of menopause. Effects on lipoprotein
      metabolism].
AB  - A number of epidemiological studies have clearly shown that post-menopausal women
      on hormone therapy (which tends to simulate normal ovarian production) have a
      reduced risk of cardiovascular disease (coronary heart disease, stroke and
      thrombotic events). In fact most of the studies have involved equine oestrogen
      (Premarin) taken orally. The effects of oestrogens and the progestins depend on
      the type of administration (oral or percutaneous administration) and the variety
      of the drug chosen and finally is also dose dependent. The most favourable effect
      is obtained in normolipidaemic women with the combination of conjugated
      oestrogens given orally and a non-androgenic progestins. Such therapy is
      associated with an increase in HDL-cholesterol and a decrease in LDL-cholesterol.
      HDL subfraction analysis shows that HDL2 are the main species involved in this
      increase. The mechanism of action of oestrogens and progestins can be summarized
      as follows: oestrogens stimulate hepatic triglyceride secretion, inhibit the
      action of hepatic lipase, augment LDL breakdown via the cellular receptor apo B-E
      and may decrease LDL oxidability and Lp(a) levels. Although several points remain
      obscure, we may notice that most of studies show that the atherogenic profile of
      the women who are currently being treated tends to improve.

PMID- 7638134
TI  - [Interventional radiology in the treatment of hemoptysis].
AB  - Massive haemoptysis, usually related to lesions of bronchial arteries, is a life
      threatening complication of chest lesions. Embolization of bronchial arteries
      demonstrates immediate favourable results in at least 90% of cases. The main
      complications of embolization of bronchial arteries are medullary strokes.
      Consequently it is mandatory to visualize the anterior spinal artery in order to
      avoid its embolization. Massive haemoptysis of pulmonary arterial origin is far
      less common. It is also feasible to perform the embolization of the abnormal
      pulmonary artery in order to control the haemoptysis.

PMID- 7638135
TI  - [Acute aortic dissection in Horton disease].

PMID- 7638136
TI  - [Muscular localization of bacillary angiomatosis].

PMID- 7638137
TI  - [Anuria caused by urinary lithiasis induced by ceftriaxone in a 6-year-old
      child].

PMID- 7638138
TI  - [Aseptic meningitis following treatment with immunoglobulins: physiopathological
      and prognostic value of screening].

PMID- 7638139
TI  - [Intermittent claudication of the lower limbs may mask another problem...!].

PMID- 7638140
TI  - [Treatment of cerebral toxoplasmosis in AIDS with cotrimoxazole].

PMID- 7638141
TI  - [Use of aspirin in coronary disease].
AB  - The beneficial effect of aspirin in different situations of coronary artery
      disease has been clearly demonstrated, but prescription remains empirical due to
      the lack of phase II trials and the incompletely understood mechanism of action.
      Since the ISIS-2 study was published in 1988, aspirin is indicated in the acute
      phase of myocardial infarction as mortality can be reduced by 20% and the rate of
      reocclusions reduced. The beneficial effect of aspirin in unstable angina has
      also been demonstrated with a reduction of more than 50% in the combined
      incidence of mortality and myocardial infarction. Stable angina is an ideal
      application for low-dose aspirin with an improvement in combined incidence of
      myocardial infarction and sudden death of 34%. The question of dose remains open.
      When prescribed for primary or secondary prevention, aspirin should be given at
      low-doses (50-100 mg/d) in a long-term regimen. The dose should be examined
      differently for treatment of acute thrombotic events including infarction and
      unstable angina. Doses above 250 mg/d with an initial dose of 500 mg to 1 g are
      recommended followed by a relay with 50 to 100 mg/d. Irreversible dose-dependent
      inhibition of platelet cyclooxygenase by aspirin is nearly total for a single
      dose of 100 mg. The effect is cumulative for smaller doses and since the
      anucleated platelets cannot resynthesize the enzyme only new platelet can recover
      enzymatic activity. The duration of the effect thus is a function of normal
      platelet turn-over (8 days). Currently, aspirin is indicated in all coronary
      artery patients and should be discussed for "potential" patients i.e. as primary
      prevention in healthy subjects at risk of coronary artery disease although the
      threshold of risk requiring prescription remains to be clearly determined.

PMID- 7638142
TI  - [Bilateral splanchnicectomy by transhiatal approach in pain of pancreatic origin.
      37 cases].
AB  - OBJECTIVES: Surgical splanchnicectomy remains a useful means to relieve pain
      induced by malignant tumours of the pancreas and chronic pancreatitis. We report
      our experience in 37 patients. METHODS: Between 1983 and 1993, 37 patients
      underwent transhiatal bilateral splanchnicectomy; 32 had a non-resectable
      adenocarcinoma and 5 chronic pancreatitis. In all cases, morphine had been
      required for pain relief. RESULTS: Symptomatic pain relief was immediately
      achieved, with complete sedation in 84.3% of the cases. Prolonged antalgic effect
      continued for the survival period in 84.3%. Mean post-operative follow-up was
      12.7 weeks corresponding to mean survival in 32 patients with pancreatic tumour.
      Post-operative mortality was 21.6% with no direct relationship with neurectomy.
      Specific morbidity related to pleural drainage was 10.8%. CONCLUSION: Compared
      with other surgical procedures, trans-hiatal bilateral splanchnicectomy is a
      simple technique which can be performed whatever the stage of the locoregional
      tumour extension. In patients without an indication for exploratory laparoscopy,
      percutaneous chemical neurolysis is still indicated, even if the long-term result
      is less effective. In case of failure or technical impossibilities, thoracoscopic
      splanchnicectomy should be performed.

PMID- 7638144
TI  - [Cerebral infarction in human immunodeficiency virus infection].
AB  - Patients infected with the human immunodeficiency virus (HIV) appear to have a
      high risk of ischaemic cerebral events. We observed two cases of cerebral
      infarction in patients with acquired immune deficiency syndrome (AIDS). In the
      first case, a 38-year-old homosexual with no cardiovascular risk other than
      smoking presented with rapidly progressive hemiparesia. Brain CT-scan visualized
      two infarcts in the territory of the right sylvian artery and the arteriography
      an occlusion of the internal carotid artery. In the second, a 37-year-old
      homosexual, hospitalization was required for a left-sided pure sensitive epilepsy
      seizure. There was no cardiovascular risk other than smoking. Magnetic resonance
      imaging showed parietal ischaemia and thrombus in the left atrium without atrial
      hypertrophy was seen at transoesophageal echocardiography. In both cases, there
      was no evidence of endocarditis, dissection of the neck vessels or disseminated
      intravascular coagulation nor of associated viral or bacterial infectious
      complication of AIDS. Angiographic findings eliminated cerebral vascularitis.
      Among the perturbed haemostasis factors previously reported in HIV+ patients, we
      observed free proteins S deficiency (68 and 43%) and heparin cofactor II
      deficiency (54 and 40%). Serum albumin was 33 and 32 g/l respectively. Outcome
      was favourable in both cases with anticoagulant therapy. These coagulation
      anomalies would not appear sufficient to explain cerebral infarction. Other
      mechanisms including immune complexed deposition, direct HIV toxicity for
      endothelial cells or the effect of cytokines on smooth muscles fibres and
      fibroblasts are probably more important causal factors.

PMID- 7638143
TI  - [Tuberculosis in a Parisian pneumology department: 151 cases].
AB  - OBJECTIVES: The incidence of tuberculosis has risen since 1992. We studied cases
      observed in our department to search for factors favouring this increased
      incidence. METHODS: A retrospective assessment of 151 cases of tuberculosis
      observed over a 3 year period in a department of pneumology in Paris was
      performed. RESULTS: Fifty-two percent of the patients were foreigners; 66% lived
      in a poor socio-economic environment included 18% with no permanent residence;
      29% were alcoholics. An association with human immunodeficiency virus infection
      was seen in 7% of the cases. Another immunodepression factor was found in 15%.
      Tuberculosis was discovered in a context of respiratory distress in 7% or the
      patients. Outcome was fatal in 6%. Three months after diagnosis 22% of the
      patients were lost to follow-up. CONCLUSION: This series emphasizes the major
      role of socio-economic factors in the rising incidence of tuberculosis and the
      need for urgent and adapted measures for therapeutic management in an often non
      compliant and socially instable population.

PMID- 7638145
TI  - [Pubic symphysitis secondary to fistula. Physiopathological hypothesis].
AB  - Symphysitis of the pubis due to Streptococcus occurred after endoscopic resection
      of the prostate in a 69-year-old man. Despite a well conducted antibiotic
      regimen, signs persisted one year later and required arthrography that showed a
      prostato-symphysis fistula. This procedure might be used to find an explanation
      of certain persistent cases of symphysitis. Fistulization between the prostate
      and the pubic symphysis would be a new pathogenic hypothesis for symphysitis of
      the pubis.

PMID- 7638146
TI  - [Current experience of myocardial revascularization with arterial bypasses].
AB  - A considerable amount of experience has been accumulated with arterial bypass
      grafting of the coronary arteries. Long-term results with the internal mammary
      artery graft have demonstrated that atheromatous complications are rare,
      permeability rate is high, post-operative cardiac events unusual and survival
      improved. These excellent results have encouraged wide use of arterial grafts and
      incited surgeons to try increasing the number of bypasses with arterial grafts.
      Current research is aimed at determining the beneficial effect of bilateral
      grafting and extensive use of the mammary artery with sequential and Y
      anastomoses. Other analogous arteries, used in situ or as free grafts. The most
      promising results have been obtained with the gastro-epiploic, the epigastric and
      the radial artery. Long-term results in patients with venous grafts alone
      demonstrate that in the future myocardial revascularization surgery will be based
      on the use of arterial grafts although a consensus on the exact nature and
      strategy of the operation remains to be established.

PMID- 7638147
TI  - [Secondary sclerosing cholangitis].
AB  - Secondary sclerosing cholangitis leads to slow and often irreversible destruction
      of the walls of both intra- and extrahepatic bile ducts. As for primary
      sclerosing cholangitis, clinical signs and laboratory findings reveal
      cholestasis. The diagnosis is confirmed by retrograde endoscopic cholangiography
      which shows narrowed bile ducts and rarefied ramifications of the intra-hepatic
      ductal system. Several causes have been identified including infectious causes
      with or without a relationship to bile duct obstruction and human
      immunodeficiency virus infection as well as ischaemic related causes after
      chemotherapy, arterial embolization or liver transplantation. Other causes
      include chemical aggression after treatment for hydatic cysts and post-surgical
      complications due to a damaged bile tract. Treatment is difficult and often
      dependent on the cause.

PMID- 7638148
TI  - [Asthma and its treatment during pregnancy].
AB  - Asthma occurs in 0.4 to 4.0% of pregnant women and is considered to be the most
      frequent respiratory disease during pregnancy. Physiological modifications during
      pregnancy, including hyperventilation due to increased progesterone levels and
      lower residual volume and functional capacity resulting from increased uterine
      volume can interfere with the asthmatic disease and require adapted management.
      Results of studies evaluating the interaction between asthma and pregnancy
      provide a wide variety of results. For some authors, manifestations of asthma may
      worsen during pregnancy requiring reinforced medical treatment in as many as 42%
      of the patients. For others bronchial hyperreactivity is significantly diminished
      during pregnancy. These findings should be examined in light of several
      individual factors including the spontaneous clinical course of asthma itself and
      more rigorous control during pregnancy. It is thus very difficult to predict the
      effect of pregnancy on clinical manifestations of asthma in any given patient or
      from one pregnancy to another. Certain authors have observed a correlation
      between IgE levels and the gravity of asthma in pregnant women: normally IgE
      levels tend to decline during pregnancy but may remain unchanged or increase if
      asthma manifestations worsen. Therapeutic options remain unchanged during
      pregnancy although only drugs proven safe for the fetus may be used. If carefully
      managed, pregnancy in the asthmatic patient usually reaches term with no major
      problem.

PMID- 7638149
TI  - [Neurosarcoidosis with dysautonomia].

PMID- 7638150
TI  - [Tracheal stenosis, an unusual mode of revealing Burkitt's lymphoma in AIDS].

PMID- 7638151
TI  - [Interstitial pneumopathy and polyarthritis after exposure to cosmetic talc].

PMID- 7638152
TI  - [Multiple coin lesions: a diagnostic pitfall, the benign metastasizing
      leiomyoma].

PMID- 7638153
TI  - [G6PD deficiency revealed by eating of beans and the ingestion of
      sulfamethoxazole].

PMID- 7638154
TI  - Tetanus immunity in young German adults.

PMID- 7638155
TI  - [A new trend toward using metal chelates in affinity chromatography of proteins
      (review)].
AB  - The main trends in the development of immobilized metal affinity chromatography
      (IMAC) over the last five years are analyzed. New chelate sorbents are described,
      and possible fields of their application are indicated. The mechanisms of
      sorption of amino acids, peptides, and proteins on immobilized metal ions are
      discussed. The potencies of IMAC in purification of natural and recombinant
      proteins and the structural examination of proteins are demonstrated. Possible
      combinations of IMAC with other methods for isolation of proteins are discussed.

PMID- 7638156
TI  - [Use of barium salts of pentoso-1-phosphoric acids in the enzymatic synthesis of
      ribothymidine and bromvinyldeoxyuridine].
AB  - The use of barium salts of ribose 1-phosphate and 2-deoxyribose-1-phosphate as
      the donors of the carbohydrate part of the required nucleosides in the reaction
      of enzymatic glycosylation of heterocyclic bases was studied. It was shown that
      application of indicated substrates in the synthesis of modified nucleosides
      ribothymidine and bromovinyldeoxyuridine, catalyzed by the nucleoside
      phosphorylases from Escherichia coli BM-11, leads to the 96-98% yield of required
      products even at an equimolar ratio of original pentose 1-phosphates and
      heterocyclic bases in the reaction mixtures.

PMID- 7638157
TI  - [Increase in the yield of recombinant proteins in Saccharomyces cerevisiae yeasts
      as a result of optimizing their culture conditions].
AB  - The optimal one-stage scheme of the cultivation of the recombinant yeast strains
      was developed. In these strains, the expression of the foreign gene is induced at
      the medium depletion by phosphorus. The scheme was tested for the producers of
      human interleukin-2 and bovine gamma-interferon. In all the strains, the yield of
      cell biomass and the production of the foreign proteins increased as compared to
      the standard two-stage cultivation. The use of the developed scheme resulted in
      the threefold increase in the yield of the target proteins and in the
      productivity of the biotechnological process.

PMID- 7638158
TI  - Sequence analysis of a mannitol dehydrogenase cDNA from plants reveals a function
      for the pathogenesis-related protein ELI3.
AB  - Mannitol is the most abundant sugar alcohol in nature, occurring in bacteria,
      fungi, lichens, and many species of vascular plants. Celery (Apium graveolens
      L.), a plant that forms mannitol photosynthetically, has high photosynthetic
      rates thought to results from intrinsic differences in the biosynthesis of
      hexitols vs. sugars. Celery also exhibits high salt tolerance due to the function
      of mannitol as an osmoprotectant. A mannitol catabolic enzyme that oxidizes
      mannitol to mannose (mannitol dehydrogenase, MTD) has been identified. In celery
      plants, MTD activity and tissue mannitol concentration are inversely related. MTD
      provides the initial step by which translocated mannitol is committed to central
      metabolism and, by regulating mannitol pool size, is important in regulating salt
      tolerance at the cellular level. We have now isolated, sequenced, and
      characterized a Mtd cDNA from celery. Analyses showed that Mtd RNA was more
      abundant in cells grown on mannitol and less abundant in salt-stressed cells. A
      protein database search revealed that the previously described ELI3 pathogenesis
      related proteins from parsley and Arabidopsis are MTDs. Treatment of celery cells
      with salicylic acid resulted in increased MTD activity and RNA. Increased MTD
      activity results in an increased ability to utilize mannitol. Among other
      effects, this may provide an additional source of carbon and energy for response
      to pathogen attack. These responses of the primary enzyme controlling mannitol
      pool size reflect the importance of mannitol metabolism in plant responses to
      divergent types of environmental stress.

PMID- 7638159
TI  - Specific binding of RNA polymerase II to the human immunodeficiency virus trans
      activating region RNA is regulated by cellular cofactors and Tat.
AB  - The regulation of human immunodeficiency virus type 1 (HIV-1) gene expression in
      response to Tat is dependent on an element downstream of the HIV-1
      transcriptional initiation site designated the trans-activating region (TAR). TAR
      forms a stable stem-loop RNA structure in which a 3-nt bulge structure and a 6-nt
      loop structure are important for Tat activation. In the absence of Tat, the HIV-1
      promoter generates so-called short or nonprocessive transcripts terminating at
      +60, while in the presence of Tat the synthesis of these short transcripts is
      markedly decreased and transcripts that extend through the 9.0-kb HIV-1 genome
      are synthesized. Tat effects on transcriptional elongation are likely due to
      alterations in the elongation properties of RNA polymerase II. In this study we
      demonstrated that a set of cellular cofactors that modulate the binding of the
      cellular protein TRP-185 to the TAR RNA loop sequences also functioned to
      markedly stimulate the specific binding of hypophosphorylated (IIa) and
      hyperphosphorylated (IIo) RNA polymerase II to TAR RNA. The concentrations of RNA
      polymerase II required for this interaction with TAR RNA were similar to those
      required to initiate in vitro transcription from the HIV-1 long terminal repeat.
      RNA gel retardation analysis with wild-type and mutant TAR RNAs indicated that
      the TAR RNA loop and bulge sequences were critical for the binding of RNA
      polymerase II. The addition of wild-type but not mutant Tat protein to gel
      retardation analysis with TAR RNA and RNA polymerase II resulted in the loss of
      binding of RNA polymerase II binding to TAR RNA. These results suggest that Tat
      may function to alter RNA polymerase II, which is paused due to its binding to
      HIV-1 TAR RNA with resultant stimulation of its transcriptional elongation
      properties.

PMID- 7638160
TI  - A channeled tRNA cycle during mammalian protein synthesis.
AB  - In earlier studies it was shown that the mammalian translation system is highly
      organized in vivo and that the intermediates in the process, aminoacyl-tRNAs, are
      channeled--i.e., they are directly transferred from the aminoacyl-tRNA
      synthetases to the elongation factor to the ribosomes without dissociating into
      the cellular fluid. Here, we examine whether spent tRNAs leaving the ribosome
      enter the fluid phase or are transferred directly to their cognate aminoacyl-tRNA
      synthetases to complete a channeled tRNA cycle. Using a permeabilized CHO cell
      system that closely mimics living cells, we find that there is no leakage of
      endogenous tRNA during many cycles of translation, and protein synthesis remains
      linear during this period, even though free aminoacyl-tRNA is known to rapidly
      equilibrate between the inside and outside of these cells. We also find that
      exogenous tRNA and periodate-oxidized tRNA have no effect on protein synthesis in
      this system, indicating that they do not enter the translation machinery, despite
      the fact that exogenous tRNA rapidly distributes throughout the cells.
      Furthermore, most of the cellular aminoacyl-tRNA synthetases function only with
      endogenous tRNAs, although a portion can use exogenous tRNA molecules. However,
      aminoacylation of these exogenous tRNAs is strongly inhibited by oxidized tRNA;
      this inhibitor has no effect on endogenous aminoacylation. On the basis of these
      and the earlier observations, we conclude that endogenous tRNA is never free of
      the protein synthetic machinery at any stage of the translation process and,
      consequently, that there is a channeled tRNA cycle during protein synthesis in
      mammalian cells.

PMID- 7638161
TI  - Apoptosis and necrosis: two distinct events induced, respectively, by mild and
      intense insults with N-methyl-D-aspartate or nitric oxide/superoxide in cortical
      cell cultures.
AB  - N-Methyl-D-aspartate (NMDA) receptor-mediated neurotoxicity may depend, in part,
      on the generation of nitric oxide (NO.) and superoxide anion (O2.-), which react
      to form peroxynitrite (OONO-). This form of neurotoxicity is thought to
      contribute to a final common pathway of injury in a wide variety of acute and
      chronic neurologic disorders, including focal ischemia, trauma, epilepsy,
      Huntington disease, Alzheimer disease, amyotrophic lateral scelerosis, AIDS
      dementia, and other neurodegenerative diseases. Here, we report that exposure of
      cortical neurons to relatively short durations or low concentrations of NMDA, S
      nitrosocysteine, or 3-morpholinosydnonimine, which generate low levels of
      peroxynitrite, induces a delayed form of neurotoxicity predominated by apoptotic
      features. Pretreatment with superoxide dismutase and catalase to scavenge O2.-
      partially prevents the apoptotic process triggered by S-nitrosocysteine or 3
      morpholinosydnonimine. In contrast, intense exposure to high concentrations of
      NMDA or peroxynitrite induces necrotic cell damage characterized by acute
      swelling and lysis, which cannot be ameliorated by superoxide dismutase and
      catalase. Thus, depending on the intensity of the initial insult, NMDA or nitric
      oxide/superoxide can result in either apoptotic or necrotic neuronal cell damage.

PMID- 7638162
TI  - The CuA center of cytochrome-c oxidase: electronic structure and spectra of
      models compared to the properties of CuA domains.
AB  - The electronic structure and spectrum of several models of the binuclear metal
      site in soluble CuA domains of cytochrome-c oxidase have been calculated by the
      use of an extended version of the complete neglect of differential
      overlap/spectroscopic method. The experimental spectra have two strong
      transitions of nearly equal intensity around 500 nm and a near-IR transition
      close to 800 nm. The model that best reproduces these features consists of a
      dimer of two blue (type 1) copper centers, in which each Cu atom replaces the
      missing imidazole on the other Cu atom. Thus, both Cu atoms have one cysteine
      sulfur atom and one imidazole nitrogen atom as ligands, and there are no bridging
      ligands but a direct Cu-Cu bond. According to the calculations, the two strong
      bands in the visible region originate from exciton coupling of the dipoles of the
      two copper monomers, and the near-IR band is a charge-transfer transition between
      the two Cu atoms. The known amino acid sequence has been used to construct a
      molecular model of the CuA site by the use of a template and energy minimization.
      In this model, the two ligand cysteine residues are in one turn of an alpha
      helix, whereas one ligand histidine is in a loop following this helix and the
      other one is in a beta-strand.

PMID- 7638163
TI  - Positive regulation of general transcription factor SIII by a tailed ubiquitin
      homolog.
AB  - General transcription factor SIII, a heterotrimer composed of 110-kDa (p110), 18
      kDa (p18), and 15-kDa (p15) subunits, increases the catalytic rate of
      transcribing RNA polymerase II by suppressing transient pausing by polymerase at
      multiple sites on DNA templates. Here we report molecular cloning and biochemical
      characterization of the SIII p18 subunit, which is found to be a member of the
      ubiquitin homology (UbH) gene family and functions as a positive regulatory
      subunit of SIII. p18 is a 118-amino acid protein composed of an 84-residue N
      terminal UbH domain fused to a 34-residue C-terminal tail. Mechanistic studies
      indicate that p18 activates SIII transcriptional activity above a basal level
      inherent in the SIII p110 and p15 subunits. Taken together, these findings
      establish a role for p18 in regulating the activity of the RNA polymerase II
      elongation complex, and they bring to light a function for a UbH domain protein
      in transcriptional regulation.

PMID- 7638164
TI  - A chloroplast processing enzyme involved in precursor maturation shares a zinc
      binding motif with a recently recognized family of metalloendopeptidases.
AB  - Nuclear-encoded proteins targeted to the chloroplast are typically synthesized
      with N-terminal transit peptides which are proteolytically removed upon import.
      Structurally related proteins of 145 and 143 kDa copurify with a soluble
      chloroplast processing enzyme (CPE) that cleaves the precursor for the major
      light-harvesting chlorophyll a/b binding protein and have been implicated in the
      maturation of the small subunit of ribulose-1,5-bisphosphate
      carboxylase/oxygenase and acyl carrier protein. The 145- and 143-kDa proteins
      have not been found as a heterodimer and thus may represent functionally
      independent isoforms encoded by separate genes. Here we describe the primary
      structure of a 140-kDa polypeptide encoded by cDNAs isolated by using antibodies
      raised against the 145/143-kDa doublet. The 140-kDa polypeptide contains a
      transit peptide, and strikingly, a His-Xaa-Xaa-Glu-His zinc-binding motif that is
      conserved in a recently recognized family of metalloendopeptidases, which
      includes Escherichia coli protease III, insulin-degrading enzyme, and subunit
      beta of the mitochondrial processing peptidase. Identity of 25-30%, concentrated
      near the N terminus of the 140-kDa polypeptide, is found with these proteases.
      Expression of CPE in leaves is not light dependent. Indeed, transcripts are
      present in dark-grown plants, and the 145/143-kDa doublet and proteolytic
      activity are both found in etioplasts, as well as in root plastids. Thus, CPE
      appears to be a necessary component of the import machinery in photosynthetic and
      nonphotosynthetic tissues, and it may function as a general stromal processing
      peptidase in plastids.

PMID- 7638165
TI  - Serotonin regulates mouse cranial neural crest migration.
AB  - Serotonergic agents (uptake inhibitors, receptor ligands) cause significant
      craniofacial malformations in cultured mouse embryos suggesting that 5
      hydroxytryptamine (serotonin) (5-HT) may be an important regulator of
      craniofacial development. To determine whether serotonergic regulation of cell
      migration might underly some of these effects, cranial neural crest (NC) explants
      from embryonic day 9 (E9) (plug day = E1) mouse embryos or dissociated mandibular
      mesenchyme cells (derived from NC) from E12 embryos were placed in a modified
      Boyden chamber to measure effects of serotonergic agents on cell migration. A
      dose-dependent effect of 5-HT on the migration of highly motile cranial NC cells
      was demonstrated, such that low concentrations of 5-HT stimulated migration,
      whereas this effect was progressively lost as the dose of 5-HT was increased. In
      contrast, most concentrations of 5-HT inhibited migration of less motile,
      mandibular mesenchyme cells. To investigate the possible involvement of specific
      5-HT receptors in the stimulation of NC migration, several 5-HT subtype-selective
      antagonists were used to block the effects of the most stimulatory dose of 5-HT
      (0.01 microM). Only NAN-190 (a 5-HT1A antagonist) inhibited the effect of 5-HT,
      suggesting involvement of this receptor. Further evidence was obtained by using
      immunohistochemistry with 5-HT receptor antibodies, which revealed expression of
      the 5-HT1A receptor but not other subtypes by migrating NC cells in both embryos
      and cranial NC explants. These results suggest that by activating appropriate
      receptors 5-HT may regulate migration of cranial NC cells and their mesenchymal
      derivatives in the mouse embryo.

PMID- 7638166
TI  - Reconsideration of the catalytic center and mechanism of mammalian
      paraoxonase/arylesterase.
AB  - For three decades, mammalian paraoxonase (A-esterase, aromatic esterase,
      arylesterase; PON, EC 3.1.8.1) has been thought to be a cysteine esterase
      demonstrating structural and mechanistic homologies with the serine esterases
      (cholinesterases and carboxyesterases). Human, mouse, and rabbit PONs each
      contain only three cysteine residues, and their positions within PON have been
      conserved. In purified human PON, residues Cys-41 and Cys-352 form an
      intramolecular disulfide bond and neither could function as an active-center
      cysteine. Highly purified, enzymatically active PON contains a single titratable
      sulfhydryl group. Thus, Cys-283 is the only probable candidate for an active
      center cysteine. Through site-directed mutagenesis of the human cDNA, Cys-283 was
      replaced with either serine (C283S) or alanine (C283A). The expressed C283 (wild
      type) enzyme was inactivated by para-hydroxymercuribenzoate, but the C283S and
      C283A mutant enzymes were not inactivated. C283A and C283S mutant enzymes
      retained both paraoxonase and arylesterase activities, and the Km values for
      paraoxon and phenyl acetate were similar to those of the wild type. Clearly,
      residue Cys-283 is free in active PON, but a free sulfhydryl group is not
      required for either paraoxonase or arylesterase activities. Consequently, it is
      necessary to examine other models for the active-site structure and catalytic
      mechanism of PON.

PMID- 7638167
TI  - Tissue specificity of a glucocorticoid-dependent enhancer in transgenic mice.
AB  - The glucocorticoid-responsive units (GRUs) of the rat tyrosine aminotransferase
      were associated with the regulatory sequences of a cellular gene expressed
      ubiquitously--that coding for the largest subunit of RNA polymerase II. In
      transient expression assays, glucocorticoid responsiveness of the hybrid
      regulatory regions depends on the spatial relationship and number of regulatory
      elements. Two parameters affect the ratio of induction by glucocorticoids: the
      basal level of the hybrid promoter that is affected by the RNA polymerase II
      regulatory sequences and the glucocorticoid-induced level that depends on the
      distance between the GRUs and the TATA box. A fully active glucocorticoid
      responsive hybrid gene was used to generate transgenic mice. Results show that a
      composite regulatory pattern is obtained: ubiquitous basal expression
      characteristic of the RNA polymerase II gene and liver-specific glucocorticoid
      activation characteristic of the tyrosine aminotransferase GRUs. This result
      demonstrates that the activity of the tyrosine aminotransferase GRUs is cell-type
      specific not only in cultured cells but also in the whole animal.

PMID- 7638168
TI  - Activation of a 15-kDa endonuclease in hypoxia/reoxygenation injury without
      morphologic features of apoptosis.
AB  - Hypoxia/reoxygenation is an important cause of tissue injury in a variety of
      organs and is classically considered to be a necrotic form of cell death. We
      examined the role of endonuclease activation, considered a characteristic feature
      of apoptosis, in hypoxia/reoxygenation injury. We demonstrate that subjecting rat
      renal proximal tubules to hypoxia/reoxygenation results in DNA strand breaks and
      DNA fragmentation (both by an in situ technique and by agarose gel
      electrophoresis), which precedes cell death. Hypoxia/reoxygenation resulted in an
      increase in DNA-degrading activity with an apparent molecular mass of 15 kDa on a
      substrate gel. This DNA-degrading activity was entirely calcium dependent and was
      blocked by the endonuclease inhibitor aurintricarboxylic acid. The protein
      extract from tubules subjected to hypoxia/reoxygenation cleaved intact nuclear
      DNA obtained from normal proximal tubules into small fragments, which further
      supports the presence of endonuclease activity. Despite unequivocal evidence of
      endonuclease activation, the morphologic features of apoptosis, including
      chromatin condensation, were not observed by light and electron microscopy.
      Endonuclease inhibitors, aurintricarboxylic acid and Evans blue, provided
      complete protection against DNA damage induced by hypoxia/reoxygenation but only
      partial protection against cell death. Taken together, our data provide strong
      evidence for a role of endonuclease activation as an early event, which is
      entirely responsible for the DNA damage and partially responsible for the cell
      death that occurs during hypoxia/reoxygenation injury. Our data also indicate
      that in hypoxia/reoxygenation injury endonuclease activation and DNA
      fragmentation occur without the morphological features of apoptosis.

PMID- 7638169
TI  - Pharmacological modulation of heat shock factor 1 by antiinflammatory drugs
      results in protection against stress-induced cellular damage.
AB  - The activation of heat shock genes by diverse forms of environmental and
      physiological stress has been implicated in a number of human diseases, including
      ischemic damage, reperfusion injury, infection, neurodegeneration, and
      inflammation. The enhanced levels of heat shock proteins and molecular chaperones
      have broad cytoprotective effects against acute lethal exposures to stress. Here,
      we show that the potent antiinflammatory drug indomethacin activates the DNA
      binding activity of human heat shock transcription factor 1 (HSF1). Perhaps
      relevant to its pharmacological use, indomethacin pretreatment lowers the
      temperature threshold of HSF1 activation, such that a complete heat shock
      response can be attained at temperatures that are by themselves insufficient. The
      synergistic effect of indomethacin and elevated temperature is biologically
      relevant and results in the protection of cells against exposure to cytotoxic
      conditions.

PMID- 7638170
TI  - Expression of endogenous peptide-major histocompatibility complex class II
      complexes derived from invariant chain-antigen fusion proteins.
AB  - CD4+ T cells recognize major histocompatibility complex (MHC) class II-bound
      peptides that are primarily obtained from extracellular sources. Endogenously
      synthesized proteins that readily enter the MHC class I presentation pathway are
      generally excluded from the MHC class II presentation pathway. We show here that
      endogenously synthesized ovalbumin or hen egg lysozyme can be efficiently
      presented as peptide-MHC class II complexes when they are expressed as fusion
      proteins with the invariant chain (Ii). Similar to the wild-type Ii, the Ii
      antigen fusion proteins were associated intracellularly with MHC molecules. Most
      efficient expression of endogenous peptide-MHC complex was obtained with fusion
      proteins that contained the endosomal targeting signal within the N-terminal
      cytoplasmic Ii residues but did not require the luminal residues of Ii that are
      known to bind MHC molecules. These results suggest that signals within the Ii can
      allow endogenously synthesized proteins to efficiently enter the MHC class II
      presentation pathway. They also suggest a strategy for identifying unknown
      antigens presented by MHC class II molecules.

PMID- 7638171
TI  - cAMP- and rapamycin-sensitive regulation of the association of eukaryotic
      initiation factor 4E and the translational regulator PHAS-I in aortic smooth
      muscle cells.
AB  - Incubating rat aortic smooth muscle cells with either platelet-derived growth
      factor BB (PDGF) or insulin-like growth factor I (IGF-I) increased the
      phosphorylation of PHAS-I, an inhibitor of the mRNA cap binding protein,
      eukaryotic initiation factor (eIF) 4E. Phosphorylation of PHAS-I promoted
      dissociation of the PHAS-I-eIF-4E complex, an effect that could partly explain
      the stimulation of protein synthesis by the two growth factors. Increasing cAMP
      with forskolin decreased PHAS-I phosphorylation and markedly increased the amount
      of eIF-4E bound to PHAS-I, effects consistent with an action of cAMP to inhibit
      protein synthesis. Both PDGF and IGF-I activated p70S6K, but only PDGF increased
      mitogen-activated protein kinase activity. Forskolin decreased by 50% the effect
      of PDGF on increasing p70S6K, and forskolin abolished the effect of IGF-I on the
      kinase. The effects of PDGF and IGF-I on increasing PHAS-I phosphorylation, on
      dissociating the PHAS-I-eIF-4E complex, and on increasing p70S6K were abolished
      by rapamycin. The results indicate that IGF-I and PDGF increase PHAS-I
      phosphorylation in smooth muscle cells by the same rapamycin-sensitive pathway
      that leads to activation of p70S6K.

PMID- 7638172
TI  - Identification of planarian homeobox sequences indicates the antiquity of most
      Hox/homeotic gene subclasses.
AB  - The homeotic gene complex (HOM-C) is a cluster of genes involved in the
      anteroposterior axial patterning of animal embryos. It is composed of homeobox
      genes belonging to the Hox/HOM superclass. Originally discovered in Drosophila,
      Hox/HOM genes have been identified in organisms as distantly related as
      arthropods, vertebrates, nematodes, and cnidarians. Data obtained in parallel
      from the organization of the complex, the domains of gene expression during
      embryogenesis, and phylogenetic relationships allow the subdivision of the
      Hox/HOM superclass into five classes (lab, pb/Hox3, Dfd, Antp, and Abd-B) that
      appeared early during metazoan evolution. We describe a search for homologues of
      these genes in platyhelminths, triploblast metazoans emerging as an outgroup to
      the great coelomate ensemble. A degenerate PCR screening for Hox/HOM homeoboxes
      in three species of triclad planarians has revealed 10 types of Antennapedia-like
      genes. The homeobox-containing sequences of these PCR fragments allowed the
      amplification of the homeobox-coding exons for five of these genes in the species
      Polycelis nigra. A phylogenetic analysis shows that two genes are clear
      orthologues of Drosophila labial, four others are members of a Dfd/Antp
      superclass, and a seventh gene, although more difficult to classify with
      certainty, may be related to the pb/Hox3 class. Together with previously
      identified Hox/HOM genes in other flatworms, our analyses demonstrate the
      existence of an elaborate family of Hox/HOM genes in the ancestor of all
      triploblast animals.

PMID- 7638173
TI  - Sp1 functions in a chromatin-dependent manner to augment human alpha-globin
      promoter activity.
AB  - The 5' flanking region of the human alpha-globin gene is highly G + C rich and
      contains multiple copies of the consensus sequence for the Sp1 binding site. We
      investigated the role of this G + C-rich region in augmenting alpha-globin
      promoter activity in the presence of the far-upstream alpha-globin enhancer, HS
      40. We show that in transiently transfected erythroid cells, deletion of the
      alpha-globin G + C-rich 5' flanking region has no effect on alpha-globin promoter
      activity. However, upon stable integration into chromatin, deletion of this
      region causes a nearly 90% decrease in promoter activity compared with expression
      from an alpha-globin promoter retaining this region. These results suggest that
      the alpha-globin G + C-rich 5' flanking region augments alpha-globin promoter
      activity in a chromatin-dependent manner. We further show that this G + C-rich
      region is required for the activation of alpha-globin gene expression during
      erythroid differentiation. Finally, we show by both footprint analysis and
      functional assays that the ability of the G + C-rich region to increase alpha
      globin promoter activity from a stably integrated alpha-globin gene is mediated
      by its multiple binding sites for the transcription factor Sp1.

PMID- 7638174
TI  - In vitro autoradiography of receptor-activated G proteins in rat brain by agonist
      stimulated guanylyl 5'-[gamma-[35S]thio]-triphosphate binding.
AB  - Agonists stimulate guanylyl 5'-[gamma-[35S]thio]-triphosphate (GTP[gamma-35S])
      binding to receptor-coupled guanine nucleotide binding protein (G proteins) in
      cell membranes as revealed in the presence of excess GDP. We now report that this
      reaction can be used to neuroanatomically localize receptor-activated G proteins
      in brain sections by in vitro autoradiography of GTP[gamma-35S] binding. Using
      the mu opioid-selective peptide [D-Ala2,N-MePhe4,Gly5-ol]enkephalin (DAMGO) as an
      agonist in rat brain sections and isolated thalamic membranes, agonist
      stimulation of GTP[gamma-35S] binding required the presence of excess GDP (1-2 mM
      GDP in sections vs. 10-30 microM GDP in membranes) to decrease basal G-protein
      activity and reveal agonist-stimulated GTP[gamma-35S] binding. Similar
      concentrations of DAMGO were required to stimulate GTP[gamma-35S] binding in
      sections and membranes. To demonstrate the general applicability of the
      technique, agonist-stimulated GTP[gamma-35S] binding in tissue sections was
      assessed with agonists for the mu opioid (DAMGO), cannabinoid (WIN 55212-2), and
      gamma-aminobutyric acid type B (baclofen) receptors. For opioid and cannabinoid
      receptors, agonist stimulation of GTP[gamma-35S] binding was blocked by
      incubation with agonists in the presence of the appropriate antagonists (naloxone
      for mu opioid and SR-141716A for cannabinoid), thus demonstrating that the effect
      was specifically receptor mediated. The anatomical distribution of agonist
      stimulated GTP[gamma-35S] binding qualitatively paralleled receptor distribution
      as determined by receptor binding autoradiography. However, quantitative
      differences suggest that variations in coupling efficiency may exist between
      different receptors in various brain regions. This technique provides a method of
      functional neuroanatomy that identifies changes in the activation of G proteins
      by specific receptors.

PMID- 7638175
TI  - Herpes simplex virus vectors overexpressing the glucose transporter gene protect
      against seizure-induced neuron loss.
AB  - We have generated herpes simplex virus (HSV) vectors vIE1GT and v alpha 4GT
      bearing the GLUT-1 isoform of the rat brain glucose transporter (GT) under the
      control of the human cytomegalovirus ie1 and HSV alpha 4 promoters, respectively.
      We previously reported that such vectors enhance glucose uptake in hippocampal
      cultures and the hippocampus. In this study we demonstrate that such vectors can
      maintain neuronal metabolism and reduce the extent of neuron loss in cultures
      after a period of hypoglycemia. Microinfusion of GT vectors into the rat
      hippocampus also reduces kainic acid-induced seizure damage in the CA3 cell
      field. Furthermore, delivery of the vector even after onset of the seizure is
      protective, suggesting that HSV-mediated gene transfer for neuroprotection need
      not be carried out in anticipation of neurologic crises. Using the bicistronic
      vector v alpha 22 beta gal alpha 4GT, which coexpresses both GT and the
      Escherichia coli lacZ marker gene, we further demonstrate an inverse correlation
      between the extent of vector expression in the dentate and the amount of CA3
      damage resulting from the simultaneous delivery of kainic acid.

PMID- 7638176
TI  - Relationship between evolutionary rate and cellular location among the Inv/Spa
      invasion proteins of Salmonella enterica.
AB  - For 21 strains of Salmonella enterica, nucleotide sequences were obtained for
      three invasion genes, spaO, spaP, and spaQ, of the chromosomal inv/spa complex,
      the products of which form a protein export system required for entry of the
      bacteria into nonphagocytic host cells. These genes are present in all eight
      subspecies of the salmonellae, and homologues occur in a variety of other
      bacteria, including the enteric pathogens Shigella and Yersinia, in which they
      are plasmid borne. Evolutionary diversification of the invasion genes among the
      subspecies of S. enterica has been generally similar in pattern and average rate
      to that of housekeeping genes. However, the range of variation in evolutionary
      rate among the invasion genes is unusually large, and there is a relationship
      between the evolutionary rate and cellular location of the invasion proteins,
      possibly reflecting diversifying selection on exported proteins in adaptation to
      variable host factors in extracellular environments. The SpaO protein, which is
      hypervariable in S. enterica and exhibits only 24% sequence identity with its
      homologues in Shigella and Yersinia, is secreted. In contrast, the membrane
      associated proteins SpaP, SpaQ, and InvA are weakly polymorphic and have > 60%
      sequence identity with the corresponding proteins of other enteric bacteria.
      Acquisition of the inv/spa genes may have been a key event in the evolution of
      the salmonellae as pathogens, following which the invention of flagellar phase
      shifting facilitated niche expansion to include warm-blooded vertebrates.

PMID- 7638177
TI  - Upregulation of class I major histocompatibility complex antigens by interferon
      gamma is necessary for T-cell-mediated elimination of recombinant adenovirus
      infected hepatocytes in vivo.
AB  - Recombinant adenoviruses are attractive vehicles for liver-directed gene therapy
      because of the high efficiency with which they transfer genes to hepatocytes in
      vivo. First generation recombinant adenoviruses deleted of E1 sequences also
      express recombinant and early and late viral genes, which lead to development of
      destructive cellular immune responses. Previous studies indicated that class I
      major histocompatibility complex (MHC)-restricted cytotoxic T lymphocytes (CTLs)
      play a major role in eliminating virus-infected cells. The present studies
      utilize mouse models to evaluate the role of T-helper cells in the primary
      response to adenovirus-mediated gene transfer to the liver. In vivo ablation of
      CD4+ cells or interferon gamma (IFN-gamma) was sufficient to prevent the
      elimination of adenovirus-transduced hepatocytes, despite the induction of a
      measurable CTL response. Mobilization of an effective TH1 response as measured by
      in vitro proliferation assays was associated with substantial upregulation of MHC
      class I expression, an effect that was prevented in IFN-gamma-deficient animals.
      These results suggest that elimination of virus-infected hepatocytes in a primary
      exposure to recombinant adenovirus requires both induction of antigen-specific
      CTLs as well as sensitization of the target cell by TH1-mediated activation of
      MHC class I expression.

PMID- 7638178
TI  - An Arabidopsis syntaxin homologue isolated by functional complementation of a
      yeast pep12 mutant.
AB  - The syntaxin family of integral membrane proteins are thought to function as
      receptors for transport vesicles, with different isoforms of this family
      localized to various membranes throughout the cell. The yeast Pep12 protein is a
      syntaxin homologue which may function in the trafficking of vesicles from the
      trans-Golgi network to the vacuole. We have isolated an Arabidopsis thaliana cDNA
      by functional complementation of a yeast pep12 mutant. The Arabidopsis cDNA
      (aPEP12) potentially encodes a 31-kDa protein which is homologous to yeast Pep12
      and to other members of the syntaxin family, indicating that this protein may
      function in the docking or fusion of transport vesicles with the vacuolar
      membrane in plant cells. Northern blot analysis indicates that the mRNA is
      expressed in all tissues examined, although at a very low level in leaves. The
      mRNA is found in all cell types in roots and leaves, as shown by in situ
      hybridization experiments. The existence of plant homologues of proteins of the
      syntaxin family indicates that the basic vesicle docking and fusion machinery may
      be conserved in plants as it is in yeast and mammals.

PMID- 7638179
TI  - Autoantibodies to calpastatin (an endogenous inhibitor for calcium-dependent
      neutral protease, calpain) in systemic rheumatic diseases.
AB  - We identified an autoantibody that reacts with calpastatin [an inhibitor protein
      of the calcium-dependent neutral protease calpain (EC 3.4.22.17)]. In early
      immunoblot studies, sera from patients with rheumatoid arthritis (RA) recognized
      unidentified 60-, 45-, and 75-kDa proteins in HeLa cell extracts. To identify
      these autoantigens, we used patient sera to clone cDNAs from a lambda gt11
      expression library. We isolated clones of four genes that expressed fusion
      proteins recognized by RA sera. The 1.2-kb cDNA insert (termed RA-6) appeared to
      encode a polypeptide corresponding to the 60-kDa antigen from HeLa cells, since
      antibodies bound to the RA-6 fusion protein also reacted with a 60-kDa HeLa
      protein. The deduced amino acid sequence of the RA-6 cDNA was completely
      identical with the C-terminal 178 amino acids of human calpastatin except for one
      amino acid substitution. Patient sera that reacted with the RA-6 also bound pig
      muscle calpastatin, and a monoclonal antibody to human calpastatin recognized the
      RA-6 fusion protein, confirming the identity of RA-6 with calpastatin. Moreover,
      the purified RA-6 fusion protein inhibited the proteolytic activity of calpain,
      and IgG from a serum containing anti-calpastatin antibodies blocked the
      calpastatin activity of the RA-6 fusion protein. Immunoblots of the RA-6 product
      detected autoantibodies to calpastatin in 57% of RA patients; this incidence was
      significantly higher than that observed in other systemic rheumatic diseases,
      including systemic lupus erythematosus (27%), polymyositis/dermatomyositis (24%),
      systemic sclerosis (38%), and overlap syndrome (29%). Thus, anti-calpastatin
      antibodies are present most frequently in patients with RA and may participate in
      pathogenic mechanisms of rheumatic diseases.

PMID- 7638180
TI  - Resistance to human immunodeficiency virus type 1 infection conferred by
      transduction of human peripheral blood lymphocytes with ribozyme, antisense, or
      polymeric trans-activation response element constructs.
AB  - Human peripheral blood lymphocytes (PBLs) were transduced with a number of
      recombinant retroviruses including RRz2, an LNL6-based virus with a ribozyme
      targeted to the human immunodeficiency virus (HIV) tat gene transcript inserted
      within the 3' region of the neomycin-resistance gene; RASH5, and LNHL-based virus
      containing an antisense sequence to the 5' leader region of HIV-1 downstream of
      the human cytomegalovirus promoter; and R20TAR, an LXSN-based virus with 20
      tandem copies of the HIV-1 trans-activation response element sequence driven by
      the Moloney murine leukemia virus long terminal repeat. After G418 selection,
      transduced PBLs were challenged with the HIV-1 laboratory strain IIIB and a
      primary clinical isolate of HIV-1, 82H. Results showed that PBLs from different
      donors could be transduced and that this conferred resistance to HIV-1 infection.
      For each of the constructs, a reduction of approximately 70% in p24 antigen level
      relative to the corresponding control-vector-transduced PBLs was observed.
      Molecular analyses showed constitutive expression of all the transduced genes
      from the retroviral long terminal repeat, but no detectable transcript was seen
      from the internal human cytomegalovirus transcript was seen from the internal
      human cytomegalovirus promoter for the antisense construct. Transduction of, and
      consequent transgene expression in, PBLs did not impact on the surface expression
      of either CD4+/CD8+ (measured by flow cytometry) or on cell doubling time
      (examined by [3H]thymidine uptake). These results indicate the potential utility
      of these anti-HIV-1 gene therapeutic agents and show the preclinical value of
      this PBL assay system.

PMID- 7638181
TI  - Integration host factor suppresses promiscuous activation of the sigma 54
      dependent promoter Pu of Pseudomonas putida.
AB  - In the presence of m-xylene, the Pu promoter of the TOL plasmid of Pseudomonas
      putida is activated by the prokaryotic enhancer-binding protein XylR. The
      intervening DNA segment between the upstream activating sequences (UASs) and
      those for RNA polymerase binding contains an integration host factor (IHF)
      attachment site that is required for full transcriptional activity. In the
      absence of IHF, the Pu promoter can be cross-activated by other members of the
      sigma 54-dependent family of regulatory proteins. Such illegitimate activation
      does not require the binding of the heterologous regulators to DNA and it is
      suppressed by bent DNA structures, either static or protein induced, between the
      promoter core elements (UAS and RNA polymerase recognition sequence). The role of
      IHF in some sigma 54 promoters is, therefore, not only a structural aid for
      assembling a correct promoter geometry but also that of an active suppressor
      (restrictor) of promiscuous activation by heterologous regulators for increased
      promoter specificity.

PMID- 7638182
TI  - Intrinsic changes in developing retinal neurons result in regenerative failure of
      their axons.
AB  - The failure of mature mammalian central nervous system axons to regenerate after
      transection is usually attributed to influences of the extraneuronal milieu.
      Using explant cocultures of retina and midbrain tectum from hamsters, we have
      found evidence that these influences account for failure of regrowth of only a
      small minority of retinal axons. For most of the axons, there is a programmed
      loss of ability to elongate in the central nervous system. We show that there is
      a precipitous decline in the ability of retinal axons to reinnervate tectal
      targets when the retina is derived from pups on or after postnatal day 2, even
      when the target is embryonic. By contrast, embryonic retinal axons can regrow
      into tectum of any age, overcoming growth-inhibiting influences of glial factors.

PMID- 7638183
TI  - Ultrafast thermally induced unfolding of RNase A.
AB  - A temperature jump (T-jump) method capable of initiating thermally induced
      processes on the picosecond time scale in aqueous solutions is introduced.
      Protein solutions are heated by energy from a laser pulse that is absorbed by
      homogeneously dispersed molecules of the dye crystal violet. These act as
      transducers by releasing the energy as heat to cause a T-jump of up to 10 K with
      a time resolution of 70 ps. The method was applied to the unfolding of RNase A.
      At pH 5.7 and 59 degrees C, a T-jump of 3-6 K induced unfolding which was
      detected by picosecond transient infrared spectroscopy of the amide I region
      between 1600 and 1700 cm-1. The difference spectral profile at 3.5 ns closely
      resembled that found for the equilibrium (native-unfolded) states. The signal at
      1633 cm-1, corresponding to the beta-sheet structure, achieved 15 +/- 2% of the
      decrease found at equilibrium, within 5.5 ns. However, no decrease in absorbance
      was detected until 1 ns after the T-ump. The disruption of beta-sheet therefore
      appears to be subject to a delay of approximately 1 ns. Prior to 1 ns after the T
      jump, water might be accessing the intact hydrophobic regions.

PMID- 7638184
TI  - A versatile vector for gene and oligonucleotide transfer into cells in culture
      and in vivo: polyethylenimine.
AB  - Several polycations possessing substantial buffering capacity below physiological
      pH, such as lipopolyamines and polyamidoamine polymers, are efficient
      transfection agents per se--i.e., without the addition of cell targeting or
      membrane-disruption agents. This observation led us to test the cationic polymer
      polyethylenimine (PEI) for its gene-delivery potential. Indeed, every third atom
      of PEI is a protonable amino nitrogen atom, which makes the polymeric network an
      effective "proton sponge" at virtually any pH. Luciferase reporter gene transfer
      with this polycation into a variety of cell lines and primary cells gave results
      comparable to, or even better than, lipopolyamines. Cytotoxicity was low and seen
      only at concentrations well above those required for optimal transfection.
      Delivery of oligonucleotides into embryonic neurons was followed by using a
      fluorescent probe. Virtually all neurons showed nuclear labeling, with no toxic
      effects. The optimal PEI cation/anion balance for in vitro transfection is only
      slightly on the cationic side, which is advantageous for in vivo delivery.
      Indeed, intracerebral luciferase gene transfer into newborn mice gave results
      comparable (for a given amount of DNA) to the in vitro transfection of primary
      rat brain endothelial cells or chicken embryonic neurons. Together, these
      properties make PEI a promising vector for gene therapy and an outstanding core
      for the design of more sophisticated devices. Our hypothesis is that its
      efficiency relies on extensive lysosome buffering that protects DNA from nuclease
      degradation, and consequent lysosomal swelling and rupture that provide an escape
      mechanism for the PEI/DNA particles.

PMID- 7638185
TI  - Restoration of surface IgM-mediated apoptosis in an anti-IgM-resistant variant of
      WEHI-231 lymphoma cells by HS1, a protein-tyrosine kinase substrate.
AB  - The HS1 protein is one of the major substrates of non-receptor-type protein
      tyrosine kinases and is phosphorylated immediately after crosslinking of the
      surface IgM on B cells. The mouse B-lymphoma cell line WEHI-231 is known to
      undergo apoptosis upon crosslinking of surface IgM by anti-IgM antibodies.
      Variants of WEHI-231 that were resistant to anti-IgM-induced apoptosis expressed
      dramatically reduced levels of HS1 protein. Expression of the human HS1 protein
      from an expression vector introduced into one of the variant cell lines restored
      the sensitivity of the cells to apoptosis induced by surface IgM crosslinking.
      These results suggest that HS1 protein plays a crucial role in the B-cell antigen
      receptor-mediated signal transduction pathway that leads to apoptosis.

PMID- 7638186
TI  - Interleukin 12 induces tyrosine phosphorylation and activation of STAT4 in human
      lymphocytes.
AB  - Interleukin 12 (IL-12) is an important immunoregulatory cytokine whose receptor
      is a member of the hematopoietin receptor superfamily. We have recently
      demonstrated that stimulation of human T and natural killer cells with IL-12
      induces tyrosine phosphorylation of the Janus family tyrosine kinase JAK2 and
      Tyk2, implicating these kinases in the immediate biochemical response to IL-12.
      Recently, transcription factors known as STATs (signal transducers and activators
      of transcription) have been shown to be tyrosine phosphorylated and activated in
      response to a number of cytokines that bind hematopoietin receptors and activate
      JAK kinases. In this report we demonstrate that IL-12 induces tyrosine
      phosphorylation of a recently identified STAT family member, STAT4, and show that
      STAT4 expression is regulated by T-cell activation. Furthermore, we show that IL
      12 stimulates formation of a DNA-binding complex that recognizes a DNA sequence
      previously shown to bind STAT proteins and that this complex contains STAT4.
      These data, and the recent demonstration of JAK phosphorylation by IL-12,
      identify a rapid signal-transduction pathway likely to mediate IL-12-induced gene
      expression.

PMID- 7638187
TI  - CD4+ blood lymphocytes are rapidly killed in vitro by contact with autologous
      human immunodeficiency virus-infected cells.
AB  - We have investigated the ability of human immunodeficiency virus (HIV)-infected
      cells to kill uninfected CD4+ lymphocytes. Infected peripheral blood mononuclear
      cells were cocultured with autologous 51Cr-labeled uninfected cells. Rapid death
      of the normal CD4-expressing target population was observed following a brief
      incubation. Death of blood CD4+ lymphocytes occurred before syncytium formation
      could be detected or productive viral infection established in the normal target
      cells. Cytolysis could not be induced by free virus, was dependent on gp120-CD4
      binding, and occurred in resting, as well as activated, lymphocytes. CD8+ cells
      were not involved in this phenomenon, since HIV-infected CEMT4 cells (CD4+, CD8-
      cells) mediated the cytolysis of uninfected targets. Reciprocal isotope-labeling
      experiments demonstrated that infected CEMT4 cells did not die in parallel with
      their targets. The uninfected target cells manifested DNA fragmentation, followed
      by the release of the 51Cr label. Thus, in HIV patients, infected lymphocytes may
      cause the depletion of the much larger population of uninfected CD4+ cells
      without actually infecting them, by triggering an apoptotic death.

PMID- 7638188
TI  - Bioenergetic scaling: metabolic design and body-size constraints in mammals.
AB  - The cytosolic phosphorylation ratio ([ATP]/[ADP][P(i)]) in the mammalian heart
      was found to be inversely related to body mass with an exponent of -0.30 (r =
      0.999). This exponent is similar to -0.25 calculated for the mass-specific O2
      consumption. The inverse of cytosolic free [ADP], the Gibbs energy of ATP
      hydrolysis (delta G'ATP), and the efficiency of ATP production (energy captured
      in forming 3 mol of ATP per cycle along the mitochondrial respiratory chain from
      NADH to 1/2 O2) were all found to scale with body mass with a negative exponent.
      On the basis of scaling of the phosphorylation ratio and free cytosolic [ADP], we
      propose that the myocardium and other tissues of small mammals represent a
      metabolic system with a higher driving potential (a higher delta G'ATP from the
      higher [ATP]/[ADP][P(i)]) and a higher kinetic gain [(delta V/Vmax)/delta [ADP]]
      where small changes in free [ADP] produce large changes in steady-state rates of
      O2 consumption. From the inverse relationship between mitochondrial efficiency
      and body size we calculate that tissues of small mammals are more efficient than
      those of large mammals in converting energy from the oxidation of foodstuffs to
      the bond energy of ATP. A higher efficiency also indicates that mitochondrial
      electron transport is not the major site for higher heat production in small
      mammals. We further propose that the lower limit of about 2 g for adult endotherm
      body size (bumblebee-bat, Estrucan shrew, and hummingbird) may be set by the
      thermodynamics of the electron transport chain. The upper limit for body size
      (100,000-kg adult blue whale) may relate to a minimum delta G'ATP of
      approximately 55 kJ/mol for a cytoplasmic phosphorylation ratio of 12,000 M-1.

PMID- 7638189
TI  - A human RNase E-like activity that cleaves RNA sequences involved in mRNA
      stability control.
AB  - We have detected an endoribonucleolytic activity in human cell extracts that
      processes the Escherichia coli 9S RNA and outer membrane protein A (ompA) mRNA
      with the same specificity as RNase E from E. coli. The human enzyme was partially
      purified by ion-exchange chromatography, and the active fractions contained a
      protein that was detected with antibodies shown to recognize E. coli RNase E. RNA
      containing four repeats of the destabilizing motif AUUUA and RNA from the 3'
      untranslated region of human c-myc mRNA were also found to be cleaved by E. coli
      RNase E and its human counterpart in a fashion that may suggest a role of this
      activity in mammalian mRNA decay. It was also found that RNA containing more than
      one AUUUA motif was cleaved more efficiently than RNA with only one or a mutated
      motif. This finding of a eukaryotic endoribonucleolytic activity corresponding to
      RNase E indicates an evolutionary conservation of the components of mRNA
      degradation systems.

PMID- 7638190
TI  - Transcription regulation by inflexibility of promoter DNA in a looped complex.
AB  - The gal operon of Escherichia coli is negatively regulated by repressor binding
      to bipartite operators separated by 11 helical turns of DNA. Synergistic binding
      of repressor to separate sites on DNA results in looping, with the intervening
      DNA as a topologically closed domain containing the two promoters. A closed DNA
      loop of 11 helical turns, which is in-flexible to torsional changes, disables the
      promoters either by resisting DNA unwinding needed for open complex formation or
      by impeding the processive DNA contacts by an RNA polymerase in flux during
      transcription initiation. Interaction between two proteins bound to different
      sites on DNA modulating the activity of the intervening segment toward other
      proteins by allostery may be a common mechanism of regulation in DNA-multiprotein
      complexes.

PMID- 7638191
TI  - Phototaxis away from blue light by an Escherichia coli mutant accumulating
      protoporphyrin IX.
AB  - The hemH gene of Escherichia coli encodes ferrochelatase (EC 4.99.1.1), the
      enzyme that catalyzes the last step in the production of heme, namely the
      synthesis of heme from protoporphyrin IX plus Fe2+. The behavioral responses to
      light were studied in E. coli carrying a hemH mutation. It was shown that the
      hemH mutant displayed a tumbling response upon illumination and a running
      response upon removal of the light. The most effect light to induce a tumbling
      response in the hemH mutant was blue light (396-450 nm). The chemotaxis machinery
      was needed for the light-induced tumbling response in the hemH mutant. The
      bacterial defect is an analog of the human inherited disease erythropoietic
      protoporphyria.

PMID- 7638192
TI  - One sequence, two folds: a metastable structure of CD2.
AB  - When expressed as part of a glutathione S-transferase fusion protein the NH2
      terminal domain of the lymphocyte cell adhesion molecule CD2 is shown to adopt
      two different folds. The immunoglobulin superfamily structure of the major (85%)
      monomeric component has previously been determined by both x-ray crystallography
      and NMR spectroscopy. We now describe the structure of a second, dimeric, form
      present in about 15% of recombinant CD2 molecules. After denaturation and
      refolding in the absence of the fusion partner, dimeric CD2 is converted to
      monomer, illustrating that the dimeric form represents a metastable folded state.
      The crystal structure of this dimeric form, refined to 2.0-A resolution, reveals
      two domains with overall similarity to the IgSF fold found in the monomer.
      However, in the dimer each domain is formed by the intercalation of two
      polypeptide chains. Hence each domain represents a distinct folding unit that can
      assemble in two different ways. In the dimer the two domains fold around a
      hydrophilic interface believed to mimic the cell adhesion interaction at the cell
      surface, and the formation of dimer can be regulated by mutating single residues
      at this interface. This unusual misfolded form of the protein, which appears to
      result from inter- rather than intramolecular interactions being favored by an
      intermediate structure formed during the folding process, illustrates that
      evolution of protein oligomers is possible from the sequence for a single protein
      domain.

PMID- 7638193
TI  - Neurosecretory vesicles can be hybrids of synaptic vesicles and secretory
      granules.
AB  - We have investigated the relationship of the so-called small dense core vesicle
      (SDCV), the major catecholamine-containing neurosecretory vesicle of sympathetic
      neurons, to synaptic vesicles containing classic neurotransmitters and secretory
      granules containing neuropeptides. SDCVs contain membrane proteins characteristic
      of synaptic vesicles such as synaptophysin and synaptoporin. However, SDCVs also
      contain membrane proteins characteristic of certain secretory granules like the
      vesicular monoamine transporter and the membrane-bound form of dopamine beta
      hydroxylase. In neurites of sympathetic neurons, synaptophysin and dopamine beta
      hydroxylase are found in distinct vesicles, consistent with their transport from
      the trans-Golgi network to the site of SDCV formation in constitutive secretory
      vesicles and secretory granules, respectively. Hence, SDCVs constitute a distinct
      type of neurosecretory vesicle that is a hybrid of the synaptic vesicle and the
      secretory granule membranes and that originates from the contribution of both the
      constitutive and the regulated pathway of protein secretion.

PMID- 7638194
TI  - 5-Methyl-2'-deoxycytidine in single-stranded DNA can act in cis to signal de novo
      DNA methylation.
AB  - Methylation of cytosine residues in DNA plays an important role in regulating
      gene expression during vertebrate embryonic development. Conversely, disruption
      of normal patterns of methylation is common in tumors and occurs early in
      progression of some human cancers. In vertebrates, it appears that the same DNA
      methyltransferase maintains preexisting patterns of methylation during DNA
      replication and carries out de novo methylation to create new methylation
      patterns. There are several indications that inherent signals in DNA structure
      can act in vivo to initiate or block de novo methylation in adjacent DNA regions.
      To identify sequences capable of enhancing de novo methylation of DNA in vitro,
      we designed a series of oligodeoxyribonucleotide substrates with substrate
      cytosine residues in different sequence contexts. We obtained evidence that some
      5-methylcytosine residues in these single-stranded DNAs can stimulate de novo
      methylation of adjacent sites by murine DNA 5-cytosine methyltransferase as
      effectively as 5-methylcytosine residues in double-stranded DNA stimulate
      maintenance methylation. This suggests that double-stranded DNA may not be the
      primary natural substrate for de novo methylation and that looped single-stranded
      structures formed during the normal course of DNA replication or repair serve as
      "nucleation" sites for de novo methylation of adjacent DNA regions.

PMID- 7638195
TI  - Lipid A biosynthesis in Rhizobium leguminosarum: role of a 2-keto-3
      deoxyoctulosonate-activated 4' phosphatase.
AB  - Lipid A from several strains of the N2-fixing bacterium Rhizobium leguminosarum
      displays significant structural differences from Escherichia coli lipid A, one of
      which is the complete absence of phosphate groups. However, the first seven
      enzymes of E. coli lipid A biosynthesis, leading from UDP-GlcNAc to the
      phosphorylated intermediate, 2-keto-3-deoxyoctulosonate (Kdo2)-lipid IVA, are
      present in R. leguminosarum. We now describe a membrane-bound phosphatase in R.
      leguminosarum extracts that removes the 4' phosphate of Kdo2-lipid IVA. The 4'
      phosphatase is selective for substrates containing the Kdo domain. It is present
      in extracts of R. leguminosarum biovars phaseoli, viciae, and trifolii but is not
      detectable in E. coli and Rhizobium meliloti. A nodulation-defective strain
      (24AR) of R. leguminosarum biovar trifolii, known to contain a 4' phosphatase
      residue on its lipid A, also lacks measurable 4' phosphatase activity. The Kdo
      dependent 4' phosphatase appears to be a key reaction in a pathway for generating
      phosphate-deficient lipid A.

PMID- 7638196
TI  - WW6: an embryonic stem cell line with an inert genetic marker that can be traced
      in chimeras.
AB  - Mutant mice produced by gene targeting in embryonic stem (ES) cells often have a
      complex or embryonic lethal phenotype. In these cases, it would be helpful to
      identify tissues and cell types first affected in mutant embryos by following the
      contribution to chimeras of ES cells homozygous for the mutant allele. Although a
      number of strategies for following ES cell development in vivo have been
      reported, each has limitations that preclude its general application. In this
      paper, we describe ES cell lines that can be tracked to every nucleated cell type
      in chimeras at all developmental stages. These lines were derived from
      blastocysts of mice that carry an 11-Mb beta-globin transgene on chromosome 3.
      The transgene is readily detected by DNA in situ hybridization, providing an
      inert, nuclear-localized marker whose presence is not affected by transcriptional
      or translational controls. The "WW" series of ES lines possess the essential
      features of previously described ES lines, including giving rise to a
      preponderance of male chimeras, all of which have to date exhibited germ-line
      transmission. In addition, clones selected for single or double targeting events
      form strong chimeras, demonstrating the feasibility of using WW6 cells to
      identify phenotypes associated with the creation of a null mutant.

PMID- 7638198
TI  - Carbohydrate gluing, an architectural mechanism in the supramolecular structure
      of an annelid giant hemoglobin.
AB  - We report a carbohydrate-dependent supramolecular architecture in the
      extracellular giant hemoglobin (Hb) from the marine worm Perinereis aibuhitensis;
      we call this architectural mechanism carbohydrate gluing. This study is an
      extension of our accidental discovery of deterioration in the form of the Hb
      caused by a high concentration of glucose. The giant Hbs of annelids are natural
      supramolecules consisting of about 200 polypeptide chains that associate to form
      a double-layered hexagonal structure. This Hb has 0.5% (wt) carbohydrates,
      including mannose, xylose, fucose, galactose, glucose, N-acetylglucosamine
      (GlcNAc), and N-acetylgalactosamine (GalNAc). Using carbohydrate-staining assays,
      in conjunction with two-dimensional polyacrylamide gel electrophoresis, we found
      that two types of linker chains (L1 and L2; the nomenclature of the Hb subunits
      followed that for another marine worm, Tylorrhynchus heterochaetus) contained
      carbohydrates with both GlcNAc and GalNAc. Furthermore, two types of globins (a
      and A) have only GlcNAc-containing carbohydrates, whereas the other types of
      globins (b and B) had no carbohydrates. Monosaccharides including mannose,
      fucose, glucose, galactose, GlcNAc, and GalNAc reversibly dissociated the intact
      form of the Hb, but the removal of carbohydrate with N-glycanase resulted in
      irreversible dissociation. These results show that carbohydrate acts
      noncovalently to glue together the components to yield the complete quaternary
      supramolecular structure of the giant Hb. We suggest that this carbohydrate
      gluing may be mediated through lectin-like carbohydrate-binding by the associated
      structural chains ("linkers").

PMID- 7638197
TI  - Transforming growth factor beta mediates the progesterone suppression of an
      epithelial metalloproteinase by adjacent stroma in the human endometrium.
AB  - Unlike most normal adult tissues, cyclic growth and tissue remodeling occur
      within the uterine endometrium throughout the reproductive years. The matrix
      metalloproteinases (MMPs), a family of structurally related enzymes that degrade
      specific components of the extracellular matrix are thought to be the
      physiologically relevant mediators of extracellular matrix composition and
      turnover. Our laboratory has identified MMPs of the stromelysin family in the
      cycling human endometrium, implicating these enzymes in mediating the extensive
      remodeling that occurs in this tissue. While the stromelysins are expressed in
      vivo during proliferation-associated remodeling and menstruation-associated
      endometrial breakdown, none of the stromelysins are expressed during the
      progesterone-dominated secretory phase of the cycle. Our in vitro studies of
      isolated cell types have confirmed progesterone suppression of stromal MMPs, but
      a stromal-derived paracrine factor was found necessary for suppression of the
      epithelial-specific MMP matrilysin. In this report, we demonstrate that
      transforming growth factor beta (TGF-beta) is produced by endometrial stroma in
      response to progesterone and can suppress expression of epithelial matrilysin
      independent of progesterone. Additionally, we find that an antibody directed
      against the mammalian isoforms of TGF-beta abolishes progesterone suppression of
      matrilysin in stromal-epithelial cocultures, implicating TGF-beta as the
      principal mediator of matrilysin suppression in the human endometrium.

PMID- 7638199
TI  - Adenoviral E1B-55kDa protein inhibits yeast mRNA export and perturbs nuclear
      structure.
AB  - The mechanisms of export of RNA from the nucleus are poorly understood; however,
      several viral proteins modulate nucleocytoplasmic transport of mRNA. Among these
      are the adenoviral proteins E1B-55kDa and E4-34kDa. Late in infection, these
      proteins inhibit export of host transcripts and promote export of viral mRNA. To
      investigate the mechanism by which these proteins act, we have expressed them in
      Saccharomyces cerevisiae. Overexpression of either or both proteins has no
      obvious effect on cell growth. By contrast, overexpression of E1B-55kDa bearing a
      nuclear localization signal (NLS) dramatically inhibits cell growth. In this
      situation, the NLS-E1B-55kDa protein is localized to the nuclear periphery,
      fibrous material is seen in the nucleoplasm, and poly(A)+ RNA accumulates in the
      nucleus. Simultaneous overexpression of E4-34kDa bearing or lacking an NLS does
      not modify these effects. We discuss the mechanisms of selective mRNA transport.

PMID- 7638200
TI  - Cre-mediated site-specific translocation between nonhomologous mouse chromosomes.
AB  - Chromosome rearrangements, such as large deletions, inversions, or
      translocations, mediate migration of large DNA segments within or between
      chromosomes, which can have major effects on cellular genetic control. A method
      for chromosome manipulation would be very useful for studying the consequences of
      large-scale DNA rearrangements in mammalian cells or animals. With the use of the
      Cre-loxP recombination system of bacteriophage P1, we induced a site-specific
      translocation between the Dek gene on chromosome 13 and the Can gene on
      chromosome 2 in mouse embryonic stem cells. The estimated frequency of Cre
      mediated translocation between the nonhomologous mouse chromosomes is
      approximately 1 in 1200-2400 embryonic stem cells expressing Cre recombinase.
      These results demonstrate the feasibility of site-specific recombination systems
      for chromosome manipulation in mammalian cells in vivo, breaking ground for
      chromosome engineering.

PMID- 7638201
TI  - Determinants of the phagocytic signal mediated by the type IIIA Fc gamma
      receptor, Fc gamma RIIIA: sequence requirements and interaction with protein
      tyrosine kinases.
AB  - The Fc gamma receptor-associated gamma and zeta subunits contain a conserved
      cytoplasmic motif, termed the immunoglobulin gene tyrosine activation motif,
      which contains a pair of YXXL sequences. The tyrosine residues within these YXXL
      sequences have been shown to be required for transduction of a phagocytic signal.
      We have previously reported that the gamma subunit of the type IIIA Fc gamma
      receptor (Fc gamma RIIIA) is approximately 6 times more efficient in mediating
      phagocytosis than the zeta subunit of Fc gamma RIIIA. By exchanging regions of
      the cytoplasmic domains of the homologous gamma and zeta chains, we observed that
      the cytoplasmic area of the gamma chain bearing a pair of the conserved YXXL
      sequences is important in phagocytic signaling. Further specificity of phagocytic
      signaling is largely determined by the two internal XX amino acids in the YXXL
      sequences. In contrast, the flanking amino acids of the YXXL sequences including
      the seven intervening amino acids between the two YXXL sequences do not
      significantly affect the phagocytic signal. Furthermore, the protein-tyrosine
      kinase Syk, but not the related kinase ZAP-70, stimulated Fc gamma RIIIA-mediated
      phagocytosis. ZAP-70, however, increased phagocytosis when coexpressed with the
      Src family kinase Fyn. These data demonstrate the importance of the two specific
      amino acids within the gamma subunit YXXL cytoplasmic sequences in phagocytic
      signaling and explain the difference in phagocytic efficiency of the gamma and
      zeta chains. These results indicate the importance of Syk in Fc gamma RIIIA
      mediated phagocytosis and demonstrate that ZAP-70 and syk differ in their
      requirement for a Src-related kinase in signal transduction.

PMID- 7638202
TI  - Atrial-like phenotype is associated with embryonic ventricular failure in
      retinoid X receptor alpha -/- mice.
AB  - We have recently characterized a cardiac model of ventricular chamber defects in
      retinoid X receptor alpha (RXR alpha) homozygous mutant (-/-) gene-targeted mice.
      These mice display generalized edema, ventricular chamber hypoplasia, and
      muscular septal defects, and they die at embryonic day 15. To substantiate our
      hypothesis that the embryos are dying of cardiac pump failure, we have used
      digital bright-field and fluorescent video microscopy and in vivo microinjection
      of fluorescein-labeled albumin to analyze cardiac function. The affected embryos
      showed depressed ventricular function (average left ventricular area ejection
      fraction, 14%), ventricular septal defects, and various degrees of
      atrioventricular block not seen in the RXR alpha wild-type (+/+) and heterozygous
      (+/-) littermates (average left ventricular area ejection fraction, 50%). The
      molecular mechanisms involved in these ventricular defects were studied by
      evaluating expression of cardiac-specific genes known to be developmentally
      regulated. By in situ hybridization, aberrant, persistent expression of the
      atrial isoform of myosin light chain 2 was identified in the ventricles. We
      hypothesize that retinoic acid provides a critical signal mediated through the
      RXR alpha pathway that is required to allow progression of development of the
      ventricular region of the heart from its early atrial-like form to the thick
      walled adult ventricle. The conduction system disturbances found in the RXR alpha
      -/- embryos may reflect a requirement of the developing conduction system for the
      RXR alpha signaling pathway, or it may be secondary to the failure of septal
      development.

PMID- 7638203
TI  - Retinoid-dependent pathways suppress myocardial cell hypertrophy.
AB  - Utilizing an in vitro model system of cardiac muscle cell hypertrophy, we have
      identified a retinoic acid (RA)-mediated pathway that suppresses the acquisition
      of specific features of the hypertrophic phenotype after exposure to the alpha
      adrenergic receptor agonist phenylephrine. RA at physiological concentrations
      suppresses the increase in cell size and induction of a genetic marker for
      hypertrophy, the atrial natriuretic factor (ANF) gene. RA also suppresses
      endothelin 1 pathways for cardiac muscle cell hypertrophy, but it does not affect
      the increase in cell size and ANF expression induced by serum stimulation. A
      trans-activation analysis using a transient transfection assay reveals that
      neonatal rat ventricular myocardial cells express functional RA receptors of both
      the retinoic acid receptor and retinoid X receptor (RAR and RXR) subtypes. Using
      synthetic agonists of RA, which selectively bind to RXR or RAR, our data indicate
      that RAR/RXR heterodimers mediate suppression of alpha-adrenergic receptor
      dependent hypertrophy. These results suggest the possibility that a pathway for
      suppression of hypertrophy may exist in vivo, which may have potential
      therapeutic value.

PMID- 7638204
TI  - Two distinct oscillators in the rat suprachiasmatic nucleus in vitro.
AB  - In the rat suprachiasmatic nucleus slice culture, circadian rhythms in the
      release of arginine vasopressin and vasoactive intestinal polypeptide were
      measured simultaneously and longitudinally. The phase relationship between the
      two peptide rhythms was relatively constant in the culture without a treatment of
      antimitotic drugs but became diverse by an introduction of antimitotics, which is
      generally used to reduce the number of glial cells. By monitoring the two rhythms
      continuously for 6 days, different periods were detected in culture with the
      antimitotic treatment. Furthermore, N-methyl-D-aspartate shifted the phase of the
      two peptide rhythms in the same culture differently. These results indicate that
      the arginine vasopressin and vasoactive intestinal polypeptide release are under
      control of different circadian oscillators.

PMID- 7638205
TI  - Multimeric complexes of the PML-retinoic acid receptor alpha fusion protein in
      acute promyelocytic leukemia cells and interference with retinoid and peroxisome
      proliferator signaling pathways.
AB  - The t(15;17) chromosomal translocation, specific for acute promyelocytic leukemia
      (APL), fuses the PML gene to the retinoic acid receptor alpha (RAR alpha) gene,
      resulting in expression of a PML-RAR alpha hybrid protein. In this report, we
      analyzed the nature of PML-RAR alpha-containing complexes in nuclear protein
      extracts of t(15;17)-positive cells. We show that endogenous PML-RAR alpha can
      bind to DNA as a homodimer, in contrast to RAR alpha that requires the retinoid X
      receptor (RXR) dimerization partner. In addition, these cells contain oligomeric
      complexes of PML-RAR alpha and endogenous RXR. Treatment with retinoic acid
      results in a decrease of PML-RAR alpha protein levels and, as a consequence, of
      DNA binding by the different complexes. Using responsive elements from various
      hormone signaling pathways, we show that PML-RAR alpha homodimers have altered
      DNA-binding characteristics when compared to RAR alpha-RXR alpha heterodimers. In
      transfected Drosophila SL-3 cells that are devoid of endogenous retinoid
      receptors PML-RAR alpha inhibits transactivation by RAR alpha-RXR alpha
      heterodimers in a dominant fashion. In addition, we show that both normal
      retinoid receptors and the PML-RAR alpha hybrid bind and activate the peroxisome
      proliferator-activated receptor responsive element from the Acyl-CoA oxidase
      gene, indicating that retinoids and peroxisome proliferator receptors may share
      common target genes. These properties of PML-RAR alpha may contribute to the
      transformed phenotype of APL cells.

PMID- 7638207
TI  - Re-expression of the alpha 2 beta 1 integrin abrogates the malignant phenotype of
      breast carcinoma cells.
AB  - To assess the role of altered alpha 2 beta 1 integrin expression in breast
      cancer, we expressed the alpha 2 beta 1 integrin de novo in a poorly
      differentiated mammary carcinoma that expressed no detectable alpha 2-integrin
      subunit. Expression of the alpha 2 beta 1 integrin resulted in a dramatic
      phenotypic alteration from a fibroblastoid, spindle-shaped, non-contact
      inhibited, motile, and invasive cell to an epithelioid, polygonal-shaped, contact
      inhibited, less motile, and less invasive cell. Although expression of the alpha
      2 subunit did not alter adhesion to collagen, it profoundly altered cell
      spreading. Re-expression of the alpha 2 beta 1 integrin restored the ability to
      differentiate into gland-like structures in three-dimensional matrices and
      markedly reduced the in vivo tumorigenicity of the cells. These results indicate
      that the consequences of diminished alpha 2 beta 1-integrin expression in the
      development of breast cancer and, presumably, of other epithelial malignancies
      are increased tumorigenicity and loss of the differentiated epithelial phenotype.

PMID- 7638206
TI  - Physical mapping of the minimal region of loss in 5q- chromosome.
AB  - Acquired interstitial loss of all or part of the long arm of human chromosome 5
      (5q-) is an anomaly that is seen frequently in patients with preleukemic
      myelodysplasia and acute myelogenous leukemia. Loss of a critical region of
      overlap at band 5q31.1 in all of these cases, with various cytogenetic breaks,
      signifies the existence of a key negative regulator of leukemogenesis. Previous
      studies have defined the proximal and distal ends of the critical region to
      reside between the genes for IL9 and EGR1, respectively. In this report, we
      describe a yeast artificial chromosome contig spanning this myeloid tumor
      suppressor locus. The combined order of the polymorphic loci is centromere-IL9
      (D5S525-D5S558-D5S89-D5S526 -D5S393)-D5S399-D5S396-D5S414-EGR1 and telomere. The
      physical distance between the IL9 and EGR1 genes is estimated to be < 2.4 Mb.
      Here we report the utility of these polymorphic loci by detecting a
      submicroscopic deletion of 5q31; an acute myelogenous leukemia patient with a
      three-way translocation, t(5;18;17)(q31;p11;q11), as the sole anomaly revealed
      allele loss of the D5S399 and D5S396 loci.

PMID- 7638208
TI  - Characterization of immature thymocyte lines derived from T-cell receptor or
      recombination activating gene 1 and p53 double mutant mice.
AB  - The T-cell receptor (TCR) beta chain is instrumental in the progression of
      thymocyte differentiation from the CD4-CD8- to the CD4+CD8+ stage. This
      differentiation step may involve cell surface expression of novel CD3-TCR
      complexes. To facilitate biochemical characterization of these complexes, we
      established cell lines from thymic lymphomas originating from mice carrying a
      mutation in the p53 gene on the one hand and a mutation in TCR-alpha, TCR-beta,
      or the recombination activating gene 1 (RAG-1) on the other hand. The cell lines
      were CD4+CD8+ and appeared to be monoclonal. A cell line derived from a RAG-1 x
      p53 double mutant thymic lymphoma expressed low levels of CD3-epsilon, -gamma,
      and -delta on the surface. TCR-alpha x p53 double mutant cell lines were found to
      express complexes consisting of TCR-beta chains associated with CD3-epsilon, 
      gamma, and -delta chains and CD3-zeta zeta dimers. These lines will be useful
      tools to study the molecular structure and signal transducing properties of
      partial CD3-TCR complexes expressed on the surface of immature thymocytes.

PMID- 7638209
TI  - Overexpression of DR-nm23, a protein encoded by a member of the nm23 gene family,
      inhibits granulocyte differentiation and induces apoptosis in 32Dc13 myeloid
      cells.
AB  - Chronic myelogenous leukemia evolves in two clinically distinct stages: a chronic
      and a blast crisis phase. The molecular changes associated with chronic phase to
      blast crisis transition are largely unknown. We have identified a cDNA clone, DR
      nm23, differentially expressed in a blast-crisis cDNA library, which has
      approximately 70% sequence similarity to the putative metastatic suppressor
      genes, nm23-H1 and nm23-H2. The deduced amino acid sequence similarity to the
      proteins encoded by these two latter genes is approximately 65% and includes
      domains and amino acid residues (the leucine zipper-like and the RGD domain, a
      serine and a histidine residue in the NH2- and in the COOH-terminal portion of
      the protein, respectively) postulated to be important for nm23 function. DR-nm23
      mRNA is preferentially expressed at early stages of myeloid differentiation of
      highly purified CD34+ cells. Its constitutive expression in the myeloid precursor
      32Dc13 cell line, which is growth-factor dependent for both proliferation and
      differentiation, results in inhibition of granulocytic differentiation induced by
      granulocyte colony-stimulating factor and causes apoptotic cell death. These
      results are consistent with a role for DR-nm23 in normal hematopoiesis and raise
      the possibility that its overexpression contributes to differentiation arrest, a
      feature of blastic transformation in chronic myelogenous leukemia.

PMID- 7638210
TI  - Plaque-associated expression of human herpesvirus 6 in multiple sclerosis.
AB  - Representational difference analysis was used to search for pathogens in multiple
      sclerosis brains. We detected a 341-nucleotide fragment that was 99.4% identical
      to the major DNA binding protein gene of human herpesvirus 6 (HHV-6). Examination
      of 86 brain specimens by PCR demonstrated that HHV-6 was present in > 70% of MS
      cases and controls and is thus a commensal virus of the human brain. By DNA
      sequencing, 36/37 viruses from MS cases and controls were typed as HHV-6 variant
      B group 2. Other herpesviruses, retroviruses, and measles virus were detected
      infrequently or not at all. HHV-6 expression was examined by immunocytochemistry
      with monoclonal antibodies against HHV-6 virion protein 101K and DNA binding
      protein p41. Nuclear staining of oligodendrocytes was observed in MS cases but
      not in controls, and in MS cases it was observed around plaques more frequently
      than in uninvolved white matter. MS cases showed prominent cytoplasmic staining
      of neurons in gray matter adjacent to plaques, although neurons expressing HHV-6
      were also found in certain controls. Since destruction of oligodendrocytes is a
      hallmark of MS, these studies suggest an association of HHV-6 with the etiology
      or pathogenesis of MS.

PMID- 7638211
TI  - Conditional expression of the ubiquitous transcription factor MafK induces
      erythroleukemia cell differentiation.
AB  - Transcription factor NF-E2 activity is thought to be crucial for the
      transcriptional regulation of many erythroid-specific genes. The three small Maf
      family proteins (MafF, MafG, and MafK) that are closely related to the c-Maf
      protooncoprotein constitute half of the NF-E2 activity by forming heterodimers
      with the large tissue-restricted subunit of NF-E2 called p45. We have established
      and characterized murine erythroleukemia cells that conditionally overexpress
      MafK from a metallothionein promoter. The conditional expression of MafK caused
      accumulation of hemoglobin, an indication of terminal differentiation along the
      erythroid pathway. Concomitantly, DNA binding activities containing MafK were
      induced within the MafK-overexpressing cells. These results demonstrate that MafK
      can promote the erythroid differentiation program in erythroleukemia cells and
      suggest that the small Maf family proteins are key regulatory molecules for
      erythroid differentiation.

PMID- 7638212
TI  - Identification of the Bacillus subtilis pur operon repressor.
AB  - Transcription of the Bacillus subtilis pur operon is repressed in response to a
      signal of excess adenine. We have purified the repressor protein and have
      identified, cloned, and overexpressed the purR regulatory gene that controls
      transcription initiation of the operon. B. subtilis purR encodes a 62-kDa
      homodimer that binds to the pur operon control region. The PurR binding site
      which overlaps the promoter encompasses approximately 110 bp. The protein-DNA
      interaction is inhibited by 5-phosphoribosyl 1-pyrophosphate. A mutation that
      deletes the repressor binding site or one that disrupts purR abolishes binding
      activity in vitro and repression of transcription in vivo in response to the
      excess adenine signal. These results lead to a model in which an excess-adenine
      signal is transmitted to PurR via the 5-phosphoribosyl 1-pyrophosphate pool. In
      addition, purR is autoregulated. There is no structural or mechanistic similarity
      between the B. subtilis and Escherichia coli purine repressors.

PMID- 7638213
TI  - Older plasma lipoproteins are more susceptible to oxidation: a linking mechanism
      for the lipid and oxidation theories of atherosclerotic cardiovascular disease.
AB  - Increases in plasma cholesterol are associated with progressive increases in the
      risk of atherosclerotic cardiovascular disease. In humans plasma cholesterol is
      contained primarily in apolipoprotein B-based low density lipoprotein (LDL).
      Cells stop making the high-affinity receptor responsible for LDL removal as they
      become cholesterol replete; this slows removal of LDL from plasma and elevates
      plasma LDL. As a result of this delayed uptake, hypercholesterolemic individuals
      not only have more LDL but have significantly older LDL. Oxidative modification
      of LDL enhances their atherogenicity. This study sought to determine whether
      increased time spent in circulation, or aging, by lipoprotein particles altered
      their susceptibility to oxidative modification. Controlled synchronous production
      of distinctive apolipoprotein B lipoproteins (yolk-specific very low density
      lipoproteins; VLDLy) with a single estrogen injection into young turkeys was used
      to model LDL aging in vivo. VLDLy remained in circulation for at least 10 days.
      Susceptibility to oxidation in vitro was highly dependent on lipoprotein age in
      vivo. Oxidation, measured as hexanal release from n-6 fatty acids in VLDLy,
      increased from 13.3 +/- 5.5 nmol of 2-day-old VLDLy per ml, to 108 +/- 17 nmol of
      7-day-old VLDLy per ml. Oxidative instability was not due to tocopherol depletion
      or conversion to a more unsaturated fatty acid composition. These findings
      establish mathematically describable linkages between the variables of LDL
      concentration and LDL oxidation. The proposed mathematical models suggest a
      unified investigative approach to determine the mechanisms for acceleration of
      atherosclerotic cardiovascular disease risk as plasma cholesterol rises.

PMID- 7638214
TI  - Structure, inheritance, and transcriptional effects of Pce1, an insertional
      element within Phanerochaete chrysosporium lignin peroxidase gene lipI.
AB  - A 1747-bp insertion within a lignin peroxidase allele of Phanerochaete
      chrysosporium BKM-F-1767 is described. Pce1, the element, lies immediately
      adjacent to the fourth intron of lip12. Southern blots reveal the presence of
      Pce1-homologous sequences in other P. chrysosporium strains. Transposon-like
      features include inverted terminal repeats and a dinucleotide (TA) target
      duplication. Atypical of transposons, Pce1 is present at very low copy numbers
      (one to five copies), and conserved transposase motifs are lacking. The mutation
      transcriptionally inactivates lip12 and is inherited in a 1:1 Mendelian fashion
      among haploid progeny. Thus, Pce1 is a transposon-like element that may play a
      significant role in generating ligninolytic variation in certain P. chrysosporium
      strains.

PMID- 7638215
TI  - Identification of four acidic amino acids that constitute the catalytic center of
      the RuvC Holliday junction resolvase.
AB  - Escherichia coli RuvC protein is a specific endonuclease that resolves Holliday
      junctions during homologous recombination. Since the endonucleolytic activity of
      RuvC requires a divalent cation and since 3 or 4 acidic residues constitute the
      catalytic centers of several nucleases that require a divalent cation for the
      catalytic activity, we examined whether any of the acidic residues of RuvC were
      required for the nucleolytic activity. By site-directed mutagenesis, we
      constructed a series of ruvC mutant genes with similar amino acid replacements in
      1 of the 13 acidic residues. Among them, the mutant genes with an alteration at
      Asp-7, Glu-66, Asp-138, or Asp-141 could not complement UV sensitivity of a ruvC
      deletion strain, and the multicopy mutant genes showed a dominant negative
      phenotype when introduced into a wild-type strain. The products of these mutant
      genes were purified and their biochemical properties were studied. All of them
      retained the ability to form a dimer and to bind specifically to a synthetic
      Holliday junction. However, they showed no, or extremely reduced, endonuclease
      activity specific for the junction. These 4 acidic residues, which are dispersed
      in the primary sequence, are located in close proximity at the bottom of the
      putative DNA binding cleft in the three-dimensional structure. From these
      results, we propose that these 4 acidic residues constitute the catalytic center
      for the Holliday junction resolvase and that some of them play a role in
      coordinating a divalent metal ion in the active center.

PMID- 7638216
TI  - Increased mutation frequency of feline immunodeficiency virus lacking functional
      deoxyuridine-triphosphatase.
AB  - Feline immunodeficiency virus (FIV) encodes the enzyme deoxyuridine
      triphosphatase (DU; EC 3.6.1.23) between the coding regions for reverse
      transcriptase and integrase in the pol gene. Here, we report the in vivo
      infection of cats with a DU- variant of the PPR strain of FIV and compare its
      growth properties and tissue distribution with those of wild-type FIV-PPR. The
      results reveal several important points: (i) DU- FIV is able to infect the cat,
      with kinetics similar to that observed with wild-type FIV; (ii) both wild-type
      and DU- FIV-infected specific-pathogen free cats mount a strong humoral antibody
      response which is able to limit the virus burden in both groups of animals; (iii)
      the virus burden is reduced in the DU- FIV-infected cats, particularly in tissues
      such as spleen and salivary gland; and (iv) the mutation frequency in DU- FIVs
      integrated in the DNA of primary macrophages after 9 months of infection is
      approximately 5-fold greater than the frequency observed in DU- FIV DNA
      integrated in T lymphocytes. Mutation rate with wild-type FIV remains the same in
      both cell types in vivo. The dominant mutations seen in macrophages with DU- FIV
      are G-->A base changes, consistent with an increased misincorporation of
      deoxyuridine into viral DNA of DU- FIVs during reverse transcription. Because
      this enzyme is absent from human immunodeficiency virus type 1 and other primate
      lentiviruses, virus replication in cell environments with low DU activity may
      lead to increased mutation and contribute to the rapid expansion of the viral
      repertoire.

PMID- 7638217
TI  - Temporal and molecular characteristics of mutations induced by ethylnitrosourea
      in germ cells isolated from seminiferous tubules and in spermatozoa of lacZ
      transgenic mice.
AB  - The lacZ transgenic mouse (Muta mouse) model was used to examine the timing of
      ethylnitrosourea (ENU)-induced mutations in germ cells. The spectrum of mutations
      was also determined. Animals received five daily treatments with ENU at 50 mg/kg
      and were sampled at times up to 55 days after treatment. In mixed germ-cell
      populations isolated from seminiferous tubules, there was little increase in the
      mutant frequency 5 days after treatment; subsequently, there was a continuous
      increase until the maximum (17.5-fold above background) was reached by
      approximately 35 days. In the spermatozoa, an increase in mutant frequency was
      not seen until 20 days after treatment, with the maximum (4.3-fold above
      background) being achieved no sooner than approximately 35 days. Based on the
      timing of sampling, these data demonstrate the detection of both spermatogonial
      and postspermatogonial, mutations. The most prominent feature of the ENU-induced
      base-pair mutations in testicular germ cells sampled 55 days after treatment is
      that 70% are induced in A.T base pairs, compared to only 16% in spontaneous
      mutations. These findings are consistent with comparable data from ENU studies
      using assays for inherited germ-cell mutations in mice. This study has
      demonstrated the utility and potential of the transgenic mouse lacZ model (Muta
      mouse) for the detection and study of germ-cell mutations and provides guidance
      in the selection of simplified treatment and sampling protocols.

PMID- 7638218
TI  - Persistent infection of rhesus macaques with T-cell-line-tropic and macrophage
      tropic clones of simian/human immunodeficiency viruses (SHIV).
AB  - To elucidate the functions of human immunodeficiency virus type 1 (HIV-1) genes
      in a nonhuman primate model, we have constructed infectious recombinant viruses
      (chimeras) between the pathogenic molecular clone of simian immunodeficiency
      virus (SIV) SIVmac239 and molecular clones of HIV-1 that differ in phenotypic
      properties controlled by the env gene. HIV-1SF33 is a T-cell-line-tropic virus
      which induces syncytia, and HIV-1SF162 is a macrophage-tropic virus that does not
      induce syncytia. A DNA fragment encoding tat, rev, and env (gp160) of SIVmac239
      has been replaced with the counterpart genetic region of HIV-1SF33 and HIV-1SF162
      to derive chimeric recombinant simian/human immunodeficiency virus (SHIV) strains
      SHIVSF33 and SHIVSF162, respectively. In the acute infection stage, macaques
      inoculated with SHIVSF33 had levels of viremia similar to macaques infected with
      SIVmac239, whereas virus loads were 1/10th to 1/100th those in macaques infected
      with SHIVSF162. Of note is the relatively small amount of virus detected in lymph
      nodes of SHIVSF162-infected macaques. In the chronic infection stage, macaques
      infected with SHIVSF33 also showed higher virus loads than macaques infected with
      SHIVSF162. Virus persists for over 1 year, as demonstrated by PCR for
      amplification of viral DNA in all animals and by virus isolation in some animals.
      Antiviral antibodies, including antibodies to the HIV-1 env glycoprotein (gp160),
      were detected; titers of antiviral antibodies were higher in macaques infected
      with SHIVSF33 than in macaques infected with SHIVSF162. Although virus has
      persisted for over 1 year after inoculation, these animals have remained healthy
      with no signs of immunodeficiency. These findings demonstrate the utility of the
      SHIV/macaque model for analyzing HIV-1 env gene functions and for evaluating
      vaccines based on HIV-1 env antigens.

PMID- 7638219
TI  - Dephosphorylation of ezrin as an early event in renal microvillar breakdown and
      anoxic injury.
AB  - Disruption of the renal proximal tubule (PT) brush border is a prominent early
      event during ischemic injury to the kidney. The molecular basis for this event is
      unknown. Within the brush border, ezrin may normally link the cytoskeleton to the
      cell plasma membrane. Anoxia causes ezrin to dissociate from the cytoskeleton and
      also causes many cell proteins to become dephosphorylated in renal PTs. This
      study examines the hypothesis that ezrin dephosphorylation accompanies and may
      mediate the anoxic disruption of the rabbit renal PT. During normoxia, 73 +/- 3%
      of the cytoskeleton-associated (Triton-insoluble) ezrin was phosphorylated, but
      88 +/- 6% of dissociated (Triton-soluble) ezrin was dephosphorylated.
      Phosphorylation was on serine/threonine resides, since ezrin was not detectable
      by an antibody against phosphotyrosine. After 60 min of anoxia, phosphorylation
      of total intracellular ezrin significantly decreased from 72 +/- 2% to 21 +/- 9%,
      and ezrin associated with the cytoskeleton decreased from 91 +/- 2% to 58 +/- 2%.
      Calyculin A (1 microM), the serine/threonine phosphatase inhibitor, inhibited the
      dephosphorylation of ezrin during anoxia by 57% and also blocked the dissociation
      of ezrin from the cytoskeleton by 53%. Our results demonstrate that (i) the
      association of ezrin with the renal microvillar cytoskeleton is correlated with
      phosphorylation of ezrin serine/threonine residues and (ii) anoxia may cause
      disruption of the renal brush border by dephosphorylating ezrin and thereby
      dissociating the brush border membrane from the cytoskeleton.

PMID- 7638220
TI  - Functional anatomy of human eyeblink conditioning determined with regional
      cerebral glucose metabolism and positron-emission tomography.
AB  - Relative cerebral glucose metabolism was examined with positron-emission
      tomography (PET) as a measure of neuronal activation during performance of the
      classically conditioned eyeblink response in 12 young adult subjects. Each
      subject received three sessions: (i) a control session with PET scan in which
      unpaired presentations of the tone conditioned stimulus and corneal airpuff
      unconditioned stimulus were administered, (ii) a paired training session to allow
      associative learning to occur, and (iii) a paired test session with PET scan.
      Brain regions exhibiting learning-related activation were identified as those
      areas that showed significant differences in glucose metabolism between the
      unpaired control condition and well-trained state in the 9 subjects who met the
      learning criterion. Areas showing significant activation included bilateral sites
      in the inferior cerebellar cortex/deep nuclei, anterior cerebellar vermis,
      contralateral cerebellar cortex and pontine tegmentum, ipsilateral inferior
      thalamus/red nucleus, ipsilateral hippocampal formation, ipsilateral lateral
      temporal cortex, and bilateral ventral striatum. Among all subjects, including
      those who did not meet the learning criterion, metabolic changes in ipsilateral
      cerebellar nuclei, bilateral cerebellar cortex, anterior vermis, contralateral
      pontine tegmentum, ipsilateral hippocampal formation, and bilateral striatum
      correlated with degree of learning. The localization to cerebellum and its
      associated brainstem circuitry is consistent with neurobiological studies in the
      rabbit model of eyeblink classical conditioning and neuropsychological studies in
      brain-damaged humans. In addition, these data support a role for the hippocampus
      in conditioning and suggest that the ventral striatum may also be involved.

PMID- 7638221
TI  - Operator binding by lambda repressor heterodimers with one or two N-terminal
      arms.
AB  - The first 6 amino acids (NH2-Ser1-Thr2-Lys3-Lys4-Lys5-Pro6) of bacteriophage
      lambda cI repressor form a flexible arm that wraps around the operator DNA.
      Homodimeric lambda repressor has two arms. To determine whether both arms are
      necessary or only one arm is sufficient for operator binding, we constructed
      heterodimeric repressors with two, one, or no arms by fusing the DNA binding
      domain of lambda repressor to leucine zippers from Fos and Jun. Although only one
      arm is visible in the cocrystal structure of the N-domain-operator complex, our
      results indicate that both arms are required for optimal operator binding and
      normal site discrimination.

PMID- 7638222
TI  - Gene for the catalytic subunit of the human DNA-activated protein kinase maps to
      the site of the XRCC7 gene on chromosome 8.
AB  - The DNA-activated serine/threonine protein kinase (DNA-PK) is composed of a large
      (approximately 460 kDa) catalytic polypeptide (DNA-PKcs) and Ku, a heterodimeric
      DNA-binding component (p70/p80) that targets DNA-PKcs to DNA. A 41-kbp segment of
      the DNA-PKcs gene was isolated, and a 7902-bp segment was sequenced. The sequence
      contains a polymorphic Pvu II restriction enzyme site, and comparing the sequence
      with that of the cDNA revealed the positions of nine exons. The DNA-PKcs gene was
      mapped to band q11 of chromosome 8 by in situ hybridization. This location is
      coincident with that of XRCC7, the gene that complements the DNA double-strand
      break repair and V(D)J recombination defects (where V is variable, D is
      diversity, and J is joining) of hamster V3 and murine severe combined
      immunodeficient (scid) cells.

PMID- 7638223
TI  - Transdifferentiation of chicken embryonic cells into muscle cells by the 3'
      untranslated region of muscle tropomyosin.
AB  - Transfection with a plasmid encoding the 3' untranslated region (3' UTR) of
      skeletal muscle tropomyosin induces chicken embryonic fibroblasts to express
      skeletal tropomyosin. Such cells become spindle shaped, fuse, and express titin,
      a marker of striated muscle differentiation. Skeletal muscle tropomyosin and
      titin organize in sarcomeric arrays. When the tropomyosin 3' UTR is expressed in
      osteoblasts, less skeletal muscle tropomyosin is expressed, and titin expression
      is delayed. Some transfected osteoblasts become spindle shaped but do not fuse
      nor organize these proteins into sarcomeres. Transfected cells expressing muscle
      tropomyosin organize muscle and nonmuscle isoforms into the same structures.
      Thus, the skeletal muscle tropomyosin 3' UTR induces transdifferentiation into a
      striated muscle phenotype in a cell-type-specific context.

PMID- 7638224
TI  - A family of Ran binding proteins that includes nucleoporins.
AB  - Ran, a small nuclear GTP binding protein, is essential for the translocation of
      nuclear proteins through the nuclear pore complex. We show that several proteins,
      including the Saccharomyces cerevisiae Nup2p and Caenorhabditis elegans F59A2.1
      nucleoporins, contain domains similar to the previously characterized murine Ran
      binding protein (RBP, termed RBP1). To test the significance of this similarity,
      we have used the corresponding domains of Nup2p and a putative S. cerevisiae RBP
      in Ran binding assays and the yeast two-hybrid system. Both proteins bind S.
      cerevisiae Ran, but only the putative S. cerevisiae RBP binds human Ran. Two
      hybrid analysis revealed Ran-Ran interactions and that yeast and human Rans can
      interact. These data identify Nup2p as a target for Ran in the nuclear pore
      complex, suggesting a direct role for it in nuclear-cytoplasmic transport. We
      discuss the possibility that proteins harboring Ran binding domains link the Ran
      GTPase cycle to specific functions in the nucleus.

PMID- 7638225
TI  - In vitro generation of hematopoietic stem cells from an embryonic stem cell line.
AB  - Hematopoietic stem cells (HSC) are unique in that they give rise both to new stem
      cells (self-renewal) and to all blood cell types. The cellular and molecular
      events responsible for the formation of HSC remain unknown mainly because no
      system exists to study it. Embryonic stem (ES) cells were induced to
      differentiate by coculture with the stromal cell line RP010 and the combination
      of interleukin (IL) 3, IL-6, and F (cell-free supernatants from cultures of the
      FLS4.1 fetal liver stromal cell line). Cell cytometry analysis of the mononuclear
      cells produced in the cultures was consistent with the presence of PgP-1+ Lin-
      early hematopoietic (B-220- Mac-1- JORO 75- TER 119-) cells and of fewer B-220+
      IgM- B-cell progenitors and JORO 75+ T-lymphocyte progenitors. The cell-sorter
      purified PgP-1+ Lin- cells produced by induced ES cells could repopulate the
      lymphoid, myeloid, and erythroid lineages of irradiated mice. The ES-derived PgP
      1+ Lin- cells must possess extensive self-renewal potential, as they were able to
      produce hematopoietic repopulation of secondary mice recipients. Indeed, marrow
      cells from irradiated mice reconstituted (15-18 weeks before) with PgP-1+ Lin-
      cell-sorter-purified cells generated by induced ES cells repopulated the
      lymphoid, myeloid, and erythroid lineages of secondary mouse recipients assessed
      16-20 weeks after their transfer into irradiated secondary mice. The results show
      that the culture conditions described here support differentiation of ES cells
      into hematopoietic cells with functional properties of HSC. It should now be
      possible to unravel the molecular events leading to the formation of HSC.

PMID- 7638226
TI  - Binding of the transcription activator NRI (NTRC) to a supercoiled DNA segment
      imitates association with the natural enhancer: an electron microscopic
      investigation.
AB  - Electron microscopic visualization indicates that the transcription activator NRI
      (NTRC) binds with exceptional selectivity and efficiency to a sequence-induced
      superhelical (spiral) segment inserted upstream of the glnA promoter, accounting
      for its observed ability to substitute for the natural glnA enhancer. The
      cooperative binding of NRI to the spiral insert leads to protein oligomerization
      which, at higher concentration, promotes selective coating of the entire
      superhelical segment with protein. Localization of NRI at apical loops is
      observed with negatively supercoiled plasmid DNA. With a linear plasmid, bending
      of DNA is observed. We confirm that NRI is a DNA-bending protein, consistent with
      its high affinity for spiral DNA. These results prove that spiral DNA without any
      homology to the NRI-binding sequence site can substitute for the glnA enhancer by
      promoting cooperative activator binding to DNA and facilitating protein
      oligomerization. Similar mechanisms might apply to other prokaryotic and
      eukaryotic activator proteins that share the ability to bend DNA and act
      efficiently as multimers.

PMID- 7638227
TI  - Thermotolerance and extended life-span conferred by single-gene mutations and
      induced by thermal stress.
AB  - We have discovered that three longevity mutants of the nematode Caenorhabditis
      elegans also exhibit increased intrinsic thermotolerance (Itt) as young adults.
      Mutation of the age-1 gene causes not only 65% longer life expectancy but also
      Itt. The Itt phenotype cosegregates with age-1. Long-lived spe-26 and daf-2
      mutants also exhibit Itt. We investigated the relationship between increased
      thermotolerance and increased life-span by developing conditions for
      environmental induction of thermotolerance. Such pretreatments at sublethal
      temperatures induce significant increases in thermotolerance and small but
      statistically highly significant increases in life expectancy, consistent with a
      causal connection between these two traits. Thus, when an animal's resistance to
      stress is increased, by either genetic or environmental manipulation, we also
      observe an increase in life expectancy. These results suggest that ability to
      respond to stress limits the life expectancy of C. elegans and might do so in
      other metazoa as well.

PMID- 7638228
TI  - Normal development and function of natural killer cells in CD3 epsilon delta
      5/delta 5 mutant mice.
AB  - The CD3 epsilon polypeptide contributes to the cell surface display as well as to
      the signal transduction properties of the T-cell antigen receptor complex.
      Intriguingly, the distribution of CD3 epsilon is not restricted to T cells, since
      activated mouse, human, and avian natural killer (NK) cells do express
      intracytoplasmic CD3 epsilon polypeptides. CD3 epsilon is also present in the
      cytoplasm of fetal thymic T/NK bipotential progenitor cells, suggesting that it
      constitutes a component of the NK differentiation program. We report here that
      the genetic disruption of CD3 epsilon exon 5 alters neither NK cell development
      nor in vitro and in vivo NK functions, although it profoundly blocked T-cell
      development. These results support the notion that CD3 epsilon is dispensable for
      mouse NK cell ontogeny and function and further suggest that the common NK/T-cell
      progenitor cell utilizes CD3 epsilon as a mandatory component only when
      differentiating toward the T-cell lineage.

PMID- 7638229
TI  - Chicken double-stranded RNA adenosine deaminase has apparent specificity for Z
      DNA.
AB  - A M(r) 140,000 protein has been purified from chicken lungs to apparent
      homogeneity. The protein binds with high affinity to a non-BNA conformation,
      which is most likely to the Z-DNA. The protein also has a binding site for double
      stranded RNA (dsRNA). Peptide sequences from this protein show similarity to
      dsRNA adenosine deaminase, an enzyme that deaminates adenosine in dsRNA to form
      inosine. Assays for this enzyme confirm that dsRNA adenosine deaminase activity
      and Z-DNA binding are properties of the same molecule. The coupling of these two
      activities in a single molecule may indicate a distinctive mechanism of gene
      regulation that is, in part, dependent on DNA topology. As such, DNA topology,
      through its effects on the efficiency and extent of RNA editing may be important
      in the generation of new phenotypes during evolution.

PMID- 7638230
TI  - Lymphocytes selected in allogeneic thymic epithelium mediate dominant tolerance
      toward tissue grafts of the thymic epithelium haplotype.
AB  - Athymic mice grafted at birth with allogeneic thymic epithelium (TE) from day 10
      embryos before hematopoietic cell colonization reconstitute normal numbers of T
      cells and exhibit full life-long tolerance to skin grafts of the TE haplotype.
      Intravenous transfers of splenic cells, from these animals to adult syngeneic
      athymic recipients, reconstitute T-cell compartments and the ability to reject
      third-party skin grafts. The transfer of specific tolerance to skin grafts of the
      TE donor strain, however, is not observed in all reconstituted recipients, and
      the fraction of nontolerant recipients increases with decreasing numbers of cells
      transferred. Furthermore, transfers of high numbers of total or CD4+ T cells from
      TE chimeras to T-cell receptor-anti-H-Y antigen transgenic immunocompetent
      syngeneic hosts specifically hinder the rejection of skin grafts of the TE
      haplotype that normally occurs in such recipients. These observations demonstrate
      (i) that mice tolerized by allogeneic TE and bearing healthy skin grafts harbor
      peripheral immunocompetent T cells capable of rejecting this very same graft; and
      (ii) that TE selects for regulatory T cells that can inhibit effector activities
      of graft-reactive cells.

PMID- 7638231
TI  - Single cell analysis of cytokine gene coexpression during CD4+ T-cell phenotype
      development.
AB  - CD4+ T cells from alpha beta-T-cell receptor transgenic mice were analyzed for
      coexpression of cytokine mRNAs during phenotype development using a double-label
      in situ hybridization technique. T cells that produced cytokines in the primary
      response were a fraction of the activated population, and only a minority of the
      cytokine-positive cells coexpressed two cytokines. In secondary responses,
      frequencies of double-positive cells increased, although they remained a minority
      of the total. Of the cytokine pairs examined, interleukin (IL)-4 and IL-5 were
      the most frequently coexpressed. IL-4 and interferon gamma showed the greatest
      tendency toward segregation of expression, being rarely coexpressed after the
      primary stimulation. These data indicate that there is significant heterogeneity
      of cytokine gene expression by individual CD4+ T cells during early antigenic
      responses. Coexpression of any pairs of cytokines, much less Th1 and Th2
      cytokines, is generally the exception. The Th0 phenotype is a population
      phenotype rather than an individual cell phenotype.

PMID- 7638232
TI  - Generation of targeted retroviral vectors by using single-chain variable
      fragment: an approach to in vivo gene delivery.
AB  - We report the generation of a retroviral vector that infects human cells
      specifically through recognition of the low density lipoprotein receptor. The
      rationale for this targeted infection is to add onto the ecotropic envelope
      protein of Moloney murine leukemia virus, normally trophic for murine cells, a
      single-chain variable fragment derived from a monoclonal antibody recognizing the
      human low density lipoprotein receptor. This chimeric envelope protein was used
      to construct a packaging cell line producing a retroviral vector capable of high
      efficiency transfer of the Escherichia coli beta-galactosidase gene to human
      cells expressing low density lipoprotein receptor. This approach offers a
      generalized plan to generate cell and tissue-specific retroviral vectors, an
      essential step toward in vivo gene therapy strategies.

PMID- 7638234
TI  - The deferred imitation task as a nonverbal measure of declarative memory.
AB  - We tested amnesic patients, patients with frontal lobe lesions, and control
      subjects with the deferred imitation task, a nonverbal test used to demonstrate
      memory abilities in human infants. On day 1, subjects were given sets of objects
      to obtain a baseline measure of their spontaneous performance of target actions.
      Then different event sequences were modeled with the object sets. On day 2, the
      objects were given to the subjects again, first without any instructions to
      imitate the sequences, and then with explicit instructions to imitate the actions
      exactly as they had been modeled. Control subjects and frontal lobe patients
      reproduced the events under both uninstructed and instructed conditions. In
      contrast, performance by the amnesic patients did not significantly differ from
      that of a second control group who had the same opportunities to handle the
      objects but were not shown the modeled actions. These findings suggest that
      deferred imitation is dependent on the brain structures essential for declarative
      memory that are damaged in amnesia, and they support the view that infants who
      imitate actions after long delays have an early capacity for long-term
      declarative memory.

PMID- 7638233
TI  - Functional and developmental studies of the peripheral arterial chemoreceptors in
      rat: effects of nicotine and possible relation to sudden infant death syndrome.
AB  - The drive on respiration mediated by the peripheral arterial chemoreceptors was
      assessed by the hyperoxic test in 3-day-old rat pups. They accounted for 22.5 +/-
      8.8% during control conditions, but only for 6.9 +/- 10.0% after nicotine
      exposure, an effect counteracted by blockade of peripheral dopamine type 2
      receptors (DA2Rs). Furthermore, nicotine reduced dopamine (DA) content and
      increased the expression of tyrosine hydroxylase (TH) in the carotid bodies,
      further suggesting that DA mediates the acute effect of nicotine on arterial
      chemoreceptor function. During postnatal development TH and DA2R mRNA levels in
      the carotid bodies decreased. Thus, nicotine from smoking may also interfere with
      the postnatal resetting of the oxygen sensitivity of the peripheral arterial
      chemoreceptors by increasing carotid body TH mRNA, as well as DA release in this
      period. Collectively these effects of nicotine on the peripheral arterial
      chemoreceptors may increase the vulnerability to hypoxic episodes and attenuate
      the protective chemoreflex response. These mechanisms may underlie the well-known
      relation between maternal smoking and sudden infant death syndrome.

PMID- 7638235
TI  - Photocleavable biotin derivatives: a versatile approach for the isolation of
      biomolecules.
AB  - While the strong biotin-avidin interaction has been widely used for the detection
      of biomolecules, its irreversibility complicates their isolation. We report the
      synthesis of a photocleavable biotin derivative (PCB) which eliminates many
      limitations of existing methods. This reagent contains a biotin moiety linked
      through a spacer arm to a photocleavable moiety, which reacts selectively with
      primary amino groups on any substrate. In experiments using [leucine]-enkephalin
      as a model substrate, we show that PCB retains its high affinity toward
      avidin/streptavidin and allows rapid (< 5 min) and efficient (> 99%) photorelease
      of the substrate in a completely unaltered form. Photocleavable biotins should be
      useful in numerous applications involving the isolation of proteins, nucleic
      acids, lipids, and cells.

PMID- 7638236
TI  - Disruption of cellular signaling pathways by daunomycin through destabilization
      of nonlamellar membrane structures.
AB  - Albeit anthracyclines are widely used in the treatment of solid tumors and
      leukemias, their mechanism of action has not been elucidated. The present study
      gives relevant information about the role of nonlamellar membrane structures in
      signaling pathways, which could explain how anthracyclines can exert their
      cytocidal action without entering the cell [Tritton, T. R. & Yee, G. (1982)
      Science 217, 248-250]. The anthracycline daunomycin reduced the formation of the
      nonlamellar hexagonal (HII) phase (i.e., the hexagonal phase propensity),
      stabilizing the bilayer structure of the plasma membrane by a direct interaction
      with membrane phospholipids. As a consequence, various cellular events involved
      in signal transduction, such as membrane fusion and membrane association of
      peripheral proteins [e.g., guanine nucleotide-binding regulatory proteins (G
      proteins and protein kinase C-alpha beta)], where nonlamellar structures
      (negative intrinsic monolayer curvature strain) are required, were altered by the
      presence of daunomycin. Functionally, daunomycin also impaired the expression of
      the high-affinity state of a G protein-coupled receptor (ternary complex for the
      alpha 2-adrenergic receptor) due to G-protein dissociation from the plasma
      membrane. In vivo, daunomycin also decreased the levels of membrane-associated G
      proteins and protein kinase C-alpha beta in the heart. The occurrence of such
      nonlamellar structures favors the association of these peripheral proteins with
      the plasma membrane and prevents daunomycin-induced dissociation. These results
      reveal an important role of the lipid component of the cell membrane in signal
      transduction and its alteration by anthracyclines.

PMID- 7638237
TI  - Molecular cloning and derived primary structure of cobra venom factor.

PMID- 7638238
TI  - Using high-efficiency mouse germline mutagenesis to investigate complex
      biological phenomena: genetic diseases, behavior, and development.
AB  - A valuable approach to investigating a biological process is to study the effect
      of mutations in the involved genes. By studying a diverse set of such mutations,
      one can gain important insights into the roles that the given gene product plays
      in the biological process. Although this approach has long been recognized, the
      scarcity of mammalian mutations has largely limited such investigations to simple
      organisms. It has recently been shown that highly efficient mutagenesis of the
      mouse germline with a random point mutagen can produce mutations that are
      valuable in several important ways. First, it can produce numerous different
      types of mutations. Second, it can be used to mutate genes that have yet to be
      cloned or characterized. Genes that have been marked by mutation can ultimately
      yield molecular access after mapping to high resolution and cloning from map
      position. Such new investigative capabilities will ultimately allow one to gain
      intimate knowledge of the molecular basis of complex biological processes like
      behavior and development. Third, mutations can be induced that yield animal
      models of human heritable diseases. Such disease models allow for intensive
      research into the etiology of the given disease and also permit the facile
      evaluation of new therapeutic regimens.

PMID- 7638239
TI  - Biological effects of power-frequency fields as they relate to carcinogenesis.
AB  - There is a widespread public perception that exposure to electricity is linked to
      cancer. The public concern stems largely from epidemiological studies which
      appear to show a relationship between cancer incidence and exposure to power
      frequency electromagnetic fields. This review will discuss the biophysics of
      power-frequency electromagnetic fields as it relates to biological effects,
      summarize the current state of the cancer epidemiology, and then concentrate on
      the laboratory studies that are relevant to addressing the possibility that power
      frequency fields are carcinogenic. Review of the epidemiological evidence shows
      that the association between exposure to power-frequency fields and cancer is
      weak and inconsistent, and generally fails to show a dose-response relationship.
      The laboratory studies of power-frequency fields show little evidence of the type
      of effects on cells or animals that point towards power-frequency fields causing
      or contributing to cancer. Finally, from what is known about the biophysics of
      power-frequency fields, there is no reason to even suspect that they would cause
      or contribute to cancer. Application of "Hill's criteria" to epidemiological and
      laboratory studies shows that the evidence for a causal association between
      exposure to power-frequency fields and the incidence of cancer is weak.

PMID- 7638240
TI  - Tumor necrosis factor-alpha in the female reproductive tract.
AB  - Tumor necrosis factor-alpha (TNF), originally identified as an inflammation
      associated cytokine, is synthesized throughout the female reproductive tract as
      well as in placentas and embryos. Development, female sex steroid hormones, and
      lipopolysaccharide influence expression of this gene. The functions of TNF may be
      determined in part by differential expression of the two species of TNF
      receptors, both of which seem to be regulated by female sex steroid hormones.
      Evidence has accumulated that supports a role for this potent, pleiotropic
      cytokine in autocrine and paracrine processes central to reproduction, including
      gamete and follicle development, steroidogenesis, uterine cyclicity, placental
      differentiation, development of the embryo, and parturition.

PMID- 7638241
TI  - Biochemical changes during growth and regression of pregnancy-dependent mammary
      tumors of GR/A mice.
AB  - The weights of pregnancy-dependent mammary tumors (PDMT) of GR/A mice continued
      to increase until parturition and decreased soon after delivery; however, mitotic
      indices in epithelial cells and stromal cells of PDMT reached a maximum plateau
      on Day 18-19 of pregnancy and decreased thereafter. Growth of PDMT in
      progesterone-treated mice on Day 15 of pregnancy was higher than that in 17 beta
      estradiol-treated mice and no treatment controls. DNA fragmentation was observed
      in PDMT on Day 20 of pregnancy and just after parturition. Two-dimensional gel
      electrophoresis of PDMT extracts revealed that five and six protein spots
      appeared newly on Day 20 of pregnancy and just after parturition, respectively. N
      terminal amino acid sequences of two of the protein spots were identical to that
      of alpha-lactalbumin. PDMT on Day 15 and 20 of pregnancy and just after
      parturition secreted matrilysin, one of the matrix metalloproteinases, which was
      identified by Western blotting. However, matrilysin was not found in hormone
      independent autonomous mammary tumors of the mouse. Estrogen receptor and c-fos
      mRNA expression levels in PDMT were high on Day 15 of pregnancy but low on Day 20
      of pregnancy and just after parturition. These findings suggest that regression
      of PDMT is caused by apoptosis, and new proteins expressed on Day 20 may
      participate in the process of regression.

PMID- 7638242
TI  - Stimulation of intestinal Na+/H+ exchange by cell volume changes during fasting
      and refeeding in rats.
AB  - Intestinal cell water was studied in rats that have been fasted then refed, two
      conditions that are known to decrease and increase, respectively, proliferation
      of the intestinal epithelium. Cell water decreased (15%) during fasting and
      returned to normal with refeeding. The amiloride-sensitive sodium uptake, which
      estimates uptake through the Na+/H+ exchange was higher in the ileum than the
      jejunum, but the jejunal uptake, unlike the ileal, was significantly increased in
      fasted/refed rats than in normally fed or fasted ones. Osmotic shrinkage of
      intestinal cells followed by restitution of their cell volume stimulated the
      Na+/H+ exchange in all of the three groups of animals, but the increase was most
      prominent in the fasted and the fasted/refed groups. Also, shrinkage of cultured
      jejunal crypt cells (IEC-6) by a hypertonic solution increased intracellular
      alkalinization that was inhibited by amiloride. The results provide evidence for
      a relationship between the change in intestinal cell size, such as that which
      occurs during fasting/refeeding, and the activation of the Na+/H+ antiport
      system. This may represent one of the signals that initiates intestinal
      proliferation in the fasting/refeeding state.

PMID- 7638243
TI  - Collagen changes in rat cervix in pregnancy--polarized light microscopic and
      electron microscopic studies.
AB  - The structural arrangement of collagen fibers in cervical ripening was studied in
      normal pregnant rats by picrosirius red staining and polarized light microscopy.
      The macromolecular arrangement of collagen fibers in the cervices of nonpregnant
      controls and in firm and rigid cervices of rats in early pregnancy (1-10 days of
      gestation) were optically anisotropic and had birefringence and a positive sign
      of elongation when examined by polarized light microscopy. The findings indicated
      that the structure of these collagen fibers was assembled from well-packed
      parallel collagen molecules. The direction of fibrous formation was arranged with
      regularity. In contrast, most of the collagen fibers in the soft cervices were
      optically isotropic. The fibers were fragmented and had a structure with
      discontinuous birefringence. Disarray and disorientation of the collagen fibers
      was found in the soft cervices. These collagen fibers changed their direction of
      formation. The disorganization of these collagen fibers might have a major impact
      on weakening the tensile strength of the cervix. Thus, we conclude that the
      processes of rearrangement of collagen fibers might be an important process in
      the cervical ripening. Electron microscopic studies suggest that in the focal
      hydrolytic processes of collagen and other matrix components degradation by
      lysosomal and phagosomal vesicles were associated with atrophic smooth muscle
      cells and fibroblasts of the cervices. Hydrolases released from lysosomes from
      these apoptotic cells may presumably be one of the processes in the remodeling of
      collagen structure.

PMID- 7638244
TI  - Supplementation with selenium restores age-related decline in immune cell
      function.
AB  - This study examined the effect of dietary (2.00 ppm for 8 weeks) supplementation
      with selenium (as sodium selenite) on the ability of lymphocytes from aged (24
      month-old), male, C57BL/6JNIA mice to respond to: (i) stimulation with mitogen
      (phytohemagglutinin) or alloantigen; (ii) develop into cytotoxic effector cells;
      and (iii) destroy tumor cells. Supplementation with selenium resulted in a
      significant increase in the ability of spleen lymphocytes from aged animals to
      undergo blastogenesis, as indicated by significantly higher amounts of nuclear
      incorporation of 3H-thymidine after stimulation with mitogen. The dietary regimen
      restored the age-related deficiency of the cells to respond to stimulation by
      nuclear DNA synthesis and cell proliferation, at least, to the level of cells
      from unsupplemented young adult animals. Furthermore, populations of in vivo,
      alloantigen-activated lymphocytes from Se-supplemented aged animals contained
      significantly higher numbers of cytotoxic lymphocytes than those from Se-normal
      aged animals, which resulted in an enhanced capacity to destroy tumor cells. The
      significant increase in the number of cytotoxic effector cells within these
      activated T-lymphocyte populations was probably the result of an enhanced clonal
      proliferation of cytotoxic precursors cells, followed by the differentiation of
      greater numbers of cytotoxic effector cells. This effect occurred in the absence
      of changes in the ability of the cells to produce IL-2, which confirmed our
      earlier observation that dietary supplementation with selenium does not affect
      the production of IL-2. The data suggested that selenium restores the age-related
      defect in cell proliferation through an increase in the number of high-affinity
      IL-2 receptors.

PMID- 7638245
TI  - In vitro effects of interactions of follicle-stimulating hormone, luteinizing
      hormone, and prolactin on progesterone synthesis by rat luteal cells during
      pregnancy.
AB  - The in vitro ability of ovine (o) follicle-stimulating hormone (FSH),
      (o)luteinizing hormone (LH), (o)prolactin (PRL), and recombinant human FSH
      (rhFSH) to stimulate progesterone (P4) synthesis by rat corpora lutea on Day 4 of
      pregnancy was investigated. Dispersed luteal cells (large + small cells) were
      incubated in the presence of the gonadotropins (1-100 ng) alone or in various
      combinations (10 ng each) for 4 or 24 hr. Given alone, all the ovine preparations
      stimulated P4 in a dose-dependent manner with even 1 ng of each hormone
      significantly enhancing P4 production. Significantly, rhFSH--which is devoid of
      LH contamination--at 10 and 100 ng also stimulated P4 production, thus clearly
      establishing for the first time that FSH is a luteotropic hormone in the rat. The
      combination of oFSH + LH + PRL (10 ng each) significantly stimulated P4 synthesis
      to a greater extent than the combination of any two hormones or individual
      hormones at both 4 hr or an additional 24 hr of incubation (P < 0.05). This
      verified in vitro a previously established in vivo luteotropic complex. One
      hundred nanamolars of phorbol 12-myristate 13-acetate (PMA) did not affect basal
      P4 secretion but inhibited cAMP, oFSH, and oLH stimulation of P4. Thus, the
      luteotropic effects of FSH, LH, and activators of protein kinase A are
      antagonized by the protein kinase C pathway.

PMID- 7638246
TI  - Effects of corticosterone in vivo and in vitro on adrenocorticotropic hormone
      production by corticotropin releasing factor-stimulated leukocytes.
AB  - Corticotropin releasing factor (CRF) and corticosterone have been shown to affect
      immune cell function. Previously, we have shown that CRF stimulates
      immunoreactive adrenocorticotropic hormone (ACTH) production by leukocytes. In
      this study, splenic leukocytes from corticosterone-injected chickens failed to
      show a CRF-induced increase in ACTH production. In addition, corticosterone in
      vitro inhibited the production of leukocyte ACTH as well as the stimulatory
      effect of CRF on splenic leukocyte ACTH production. These findings show that, as
      with anterior pituitary ACTH production, CRF-stimulated leukocyte ACTH production
      is inhibited by glucocorticoids.

PMID- 7638247
TI  - A vasoactive intestinal peptide binding component in hen granulosa cells.
AB  - In radioligand assays, the vasoactive intestinal peptide (VIP) binding component
      in the membrane fraction of granulosa cells of the ovary of the hen was shown to
      possess characteristic properties of a receptor, such as reversible binding,
      binding specificity, high-affinity, and limited capacity. The binding site was of
      a single class. The binding affinity was higher in the largest (F1) and the
      second largest follicle (F2) than in the third largest follicle (F3), and the
      binding capacity was greater in F2 and F3 than in F1. During the ovulatory cycle,
      changes in affinity and capacity were observed only in F1 shortly before
      ovulation. The results suggest the presence of VIP receptor in the hen granulosa
      cells and its binding is assumed to be related to the follicular growth and
      ovulation.

PMID- 7638248
TI  - Effects of prolactin on galactosyl transferase and alpha-lactalbumin mRNA
      accumulation in mouse mammary gland explants.
AB  - Studies were carried out to determine the possible mechanism(s) by which
      prolactin (PRL) stimulates alpha-lactalbumin and galactosyl transferase activity
      in cultured mouse mammary tissues. In earlier studies it was shown that the onset
      of the PRL stimulation of galactosyl transferase activity occurs between 4 and 8
      hr after adding prolactin to cultured mouse mammary gland explants, and a maximum
      effect is evoked by 24 hr. In contrast, an effect of prolactin on alpha
      lactalbumin activity occurred 24 hr after adding PRL to mammary gland cultures,
      but not at earlier times. In the present studies, it is shown that prolactin
      effects an increased tissue accumulation of mRNAs for both alpha-lactalbumin and
      galactosyl transferase after a 4 to 6 hr culture with prolactin. The lowest
      concentration of prolactin that stimulates the accumulation of both galactosyl
      transferase and alpha-lactalbumin mRNA is approximately 10 ng/ml, and a maximum
      response is achieved with 200 ng/ml. Thus, it is likely that the effect of PRL on
      the activity of galactosyl transferase is causally associated with the effect of
      prolactin on the accumulation of its mRNAs. However, the PRL stimulation of alpha
      lactalbumin activity is not temporally associated with the tissue accumulation of
      the mRNA for alpha-lactalbumin.

PMID- 7638249
TI  - Menhaden oil feeding increases potential for renal free radical production in
      BHE/cdb rats.
AB  - The effects of feeding 9% beef tallow (BT) or menhaden oil (MO) in a 10% fat-60%
      sucrose-20% protein diet on renal cortex fatty acid profile, renal lipid peroxide
      formation potential, and the blood pressure response to a norepinephrine
      challenge was studied. Male weanling BHE/cdb prediabetic rats were studied after
      8 weeks of diet treatment. Half the rats were subjected to a norepinephrine
      challenge, and their mean arterial blood pressure was determined. Plasma renin
      and angiotensin II levels were determined in the presence or absence of the
      challenge. The source of dietary fat had no effect on these measurements. MO fed
      rats had a greater potential to form lipid free radicals in the kidney than BT
      fed rats despite the fact that the renal tissue from both groups had an
      equivalent number of unsaturations on a mole % basis. From these results we
      conclude that the accelerated renal disease in menhaden oil fed rats is not due
      to a diet fat effect on blood pressure regulation but might be due to a diet fat
      effect on free radical production. These free radicals can be cytotoxic and if
      produced in large amounts could result in a loss of glomerular cells. Whether
      this occurs and can be reversed by a change in diet was not determined.

PMID- 7638250
TI  - Comparative distribution, metabolism, and utilization of phylloquinone and
      menaquinone-9 in rat liver.
AB  - The liver of most species contains a spectrum of bacterially produced menaquinone
      homologs as well as the major dietary form of vitamin K, phylloquinone. The
      relative utilization of phylloquinone and menaquinone-9 (MK-9) as substrates for
      the microsomal vitamin K-dependent gamma-glutamyl carboxylase was determined in a
      rat model. Vitamin K 2,3-epoxide, the co-product of the carboxylation reaction,
      is recycled to the quinone form of the vitamin by a microsomal vitamin K epoxide
      reductase. This enzyme activity was blocked by warfarin administration, and the
      appearance of the hepatic epoxides of phylloquinone and MK-9 was determined as a
      measure of their utilization by the carboxylase. When the liver contained
      equimolar amounts of phylloquinone and MK-9, four times as much phylloquinone
      epoxide as MK-9 epoxide was present in the liver 1 hr after warfarin
      administration. These data suggest that hepatic MK-9 is not as efficiently
      utilized as phylloquinone. The data obtained have also demonstrated a previously
      unrecognized difference in phylloquinone and menaquinone metabolism. MK-9
      epoxide, and to a lesser extent MK-9, was preferentially localized in the
      mitochondria, while higher concentrations of phylloquinone were found in the
      microsomes.

PMID- 7638251
TI  - Regulation of rabbit erythrocyte Ca(2+)-pump sensitivity to calmodulin in
      experimental hyperlipidemia.
AB  - Intracellular free calcium activity is in part determined by a calmodulin
      regulated plasma membrane Ca(2+)-pump. Since changes in Ca2+ permeability have
      been implicated in atherosclerotic plaque formation, we initiated a lipid
      hyperalimentation protocol during which we measured various erythrocyte calcium
      flux parameters and early atheroma development. Adolescent New Zealand White
      rabbits were fed a diet with 0.5% cholesterol and 2.5% lard over a 3-month
      period. Plasma cholesterol and triacylglycerols increased on average 18.7- and
      13.9-fold respectively, while erythrocyte membrane cholesterol content decreased
      18% and total phospholipids by 54%. After 3 months of lipid hyperalimentation,
      22% of the aortic arch was covered with large, early-stage, raised atheroma.
      Basal and calmodulin-activated (Ca2+ + Mg2+)-ATPase activities in erythrocyte
      membranes increased by 31% and 123%, respectively at 2 months, with a concomitant
      increase in calmodulin affinity (Km) from 15.6 to 4.2 nM. These differences were
      transient on account of changes in the control animals which exhibited a slowly
      developing sensitivity to calmodulin during maturation. Basal Ca2+ transport and
      passive Ca2+ permeability increased about 7-fold during the hyperlipidemic phase.
      This suggests that overt hyperlipidemia, leading to atherosclerotic plaque
      development, alters plasma membrane Ca2+ regulatory mechanisms including passive
      Ca2+ permeability. The changes in enzymatic function, membrane composition, and
      Ca2+ permeability seen in this red cell model system may be a reflection of early
      changes in cells that are directly involved in the development of atherosclerotic
      plaques.

PMID- 7638252
TI  - Invertebrate visual pigments.

PMID- 7638253
TI  - Increased UV exposure in Finland in 1993.
AB  - Exceptionally low total ozone, up to 40% below the normal level, was measured
      over Northern Europe during winter and spring in 1992 and 1993. In 1993 the
      depletion persisted up to the end of May, resulting in a significant increase of
      biologically effective UV radiation. The increases were significantly smaller in
      1992 and 1993 than in 1993. The UV exposure of the Finnish population was
      evaluated through measurements and theoretical calculations. The increase in
      measured erythemal (International Lighting Commission) UV falling onto horizontal
      surfaces on clear day was determined relative to model calculations for an
      average ozone amount. The increase was on average 10% from April to May 1993, and
      the maximal measured increase was 34%. Theoretical calculations for both
      erythemal and carcinogenic (Skin Cancer Utrecht--Philadelphia) UV indicated that
      in 1993 the theoretical annual increase to a vertical (cylinder) surface ranged
      from 8 to 13% in Finland. The reflection of UV from snow considerably increases
      facial UV doses in Northern Finland.

PMID- 7638254
TI  - Spectral dependence of UV-induced immediate and delayed apoptosis: the role of
      membrane and DNA damage.
AB  - The phototoxicity of each waveband region of UV radiation (UVR), i.e., UVA (320
      400 nm), UVB (290-320 nm) and UVC (200-290 nm), was correlated with an apoptotic
      mechanism using equilethal doses (10% survival) on murine lymphoma L5178Y-R
      cells. Apoptosis was qualitatively monitored for DNA "ladder" formation
      (multiples of 200 base pair units) using agarose gel electrophoresis, while the
      percentages of apoptotic and membrane-permeabilized cells were quantified over a
      postexposure time course using flow cytometry. The UVA1 radiation (340-400 nm)
      induced both an immediate (< 4 h) and a delayed (> 20 h) apoptotic mechanism,
      while UVB or UVC radiation induced only the delayed mechanism. The role of
      membrane damage was examined using a lipophilic free-radical scavenger, vitamin
      E. Immediate apoptosis and membrane permeability increased in a UVA1 dose
      dependent manner, both of which were reduced by vitamin E. However, vitamin E had
      little effect on UVR-induced delayed apoptosis. In contrast, the DNA damaging
      agents 2,4- and 2,6-diaminotoluene exclusively induced delayed apoptosis. Thus,
      immediate apoptosis can be initiated by UVA1-induced membrane damage, while
      delayed apoptosis can be initiated by DNA damage. Moreover, the results suggest
      that immediate and delayed apoptosis are two independent mechanisms that exist
      beyond the realm of photobiology.

PMID- 7638255
TI  - Subcellular localization of and photosensitization by protoporphyrin IXhuman
      keratinocytes and fibroblasts cultivated with 5-aminolevulinic acid.
AB  - The subcellular localization of protoporphyrin (PP) has been studied by
      microspectrofluorometric techniques in NCTC 2544 keratinocytes incubated with 5
      aminolevulinic acid (ALA) for times up to 42 h. Whereas the plasma membrane shows
      strong staining, fluorescent spots are observed within the cytoplasm especially
      in the perinuclear region. Although the topographic pattern of the PP
      distribution does not change much with the incubation time with ALA, the
      fluorescence spectra suggest that the PP microenvironments are quite different at
      short and long incubation times. Addition of 18 microM desferrioxamine almost
      doubles the ALA-induced PP concentration. Colocalization experiments with
      rhodamine 123, a mitochondrial probe, and lucifer yellow (LY) or neutral red
      (NR), two lysosome probes, demonstrate that at least some of these spots are of
      lysosomal origin. Study of the time evolution of the NR fluorescence under
      irradiation with visible light in the presence and absence of ALA demonstrates
      that lysosomes are damaged cells that have synthesized PP. No PP fluorescence can
      be detected in mitochondria after incubation with ALA. However,
      photosensitization of mitochondria occurs under irradiation with visible light.
      Very little formation of lipofuscins by photosensitization with exogenous PP or
      ALA-induced PP is observed with the NCTC 2544 keratinocytes, as compared to
      normal human fibroblasts.

PMID- 7638256
TI  - Catalase inactivation following photosensitization with tetrasulfonated
      metallophthalocyanines.
AB  - Catalase (CAT) in solution or incorporated in erythrocytes and K562 leukemic
      cells is inactivated during photosensitization with tetrasulfonated
      metallophthalocyanines (MePcS4). The effect of added scavengers and D2O showed
      that both singlet oxygen and free radical species are involved in this process.
      Evidence was found that direct interactions of ground or excited-stated
      photosensitizer with CAT are not responsible for CAT inactivation. Specific
      techniques to probe early damage to the CAT structure involved optical and EPR
      spectroscopy, HPLC and polyacrylamide gel electrophoresis analyses. Different
      primary events of photosensitized protein damage included oxidation of cysteine
      residues as well as other amino acids, as demonstrated by the formation of carbon
      centered free radicals and the loss of absorbance at lambda = 275 nm. In
      parallel, we detected degradation of the CAT heme groups, accompanied by release
      of Fe(II) ions in solution. These combined phenomena initiate cross-linkages
      between CAT subunits and subsequent degradation of the protein with formation of
      irreversible aggregates in solution. Phthalocyanine-mediated photoinactivation of
      cell-bound CAT results in loss of protection against accumulating H2O2, providing
      an additional pathway of phototoxicity.

PMID- 7638257
TI  - Elevation of GRP-78 and loss of HSP-70 following photodynamic treatment of V79
      cells: sensitization by nigericin.
AB  - Chinese hamster V79 cells were treated with photodynamic therapy (PDT) sensitized
      by aluminum phthalocyanine (AlPc) or with the ionophore nigericin or with
      combinations of PDT and nigericin. We previously showed that PDT and nigericin
      interact synergistically in the killing of these cells; i.e. doses of PDT that
      kill no more than 10% of the cells in combination with nontoxic exposures to
      nigericin lead to a loss of clonogenicity of three to five orders of magnitude.
      Photodynamic therapy induces an enhanced rate of expression of the stress gene
      grp-78 both at the transcriptional and translational levels and causes a decrease
      in the synthesis of the constitutive heat shock protein HSP-70 as well as in
      expression of HSP-70 mRNA. When the cells are exposed to PDT in the presence of
      nigericin, these effects are elicited at three- to four-fold lower PDT doses.
      Thus, PDT in the presence of nigericin is much more effective in inducing the
      changes in gene expression than is PDT alone. In the absence of nigericin the PDT
      dose inducing a two-fold increase in GRP-78 accumulation causes little or no loss
      of clonogenicity. In the presence of nigericin, however, the PDT dose leading to
      a similar change in GRP-78 level produces up to a 50% loss of clonogenicity. The
      fact that nigericin is dose-modifying for both cell killing and stress responses
      suggests that nigericin either increases the yield of oxidative damage from a
      given dose of PDT or magnifies the cellular response to a constant level of
      oxidative stress.

PMID- 7638258
TI  - Inactivation of cell surface receptors by pheophorbide a, a green pigment
      isolated from Psychotria acuminata.
AB  - The inhibition of cytokine and monoclonal antibody binding cell surfaces caused
      by an extract of Psychotria acuminata, a medicinal plant used in the traditional
      medicine of the people of Belize (Central Africa), was attributed to the presence
      of pheophorbide a and pyropheophorbide a. Since the binding of tumor necrosis
      factor-alpha, interleukin-8, complement factor 5a as well as epidermal growth
      factor to target cells was dramatically reduced, the inhibition was not receptor
      or cytokine specific. In addition, the respective binding of radiolabeled
      monoclonal antibodies CL203 and R15.7 to the cell surface antigens intracellular
      cell adhesion molecule-1 and lymphocyte function-associated antigen-1 beta-chain
      was decreased by pretreatment of cells with pheophorbide a as well. In all cases,
      the inhibition by pheophorbides was dependent on the simultaneous presence of
      light, indicating causative involvement of a photodynamic process. These
      observations are not unique to pheophorbides and can be extended to porphyrins as
      well as to other photodynamic agents. Cytotoxicity resulting from photodynamic
      therapy (PDT) has been documented by many studies. Our investigations suggest
      that the inactivation of cell surface receptors contributes not only to an
      antitumor effect of PDT but also to the systemic immunosuppression, a serious
      side effect of PDT.

PMID- 7638259
TI  - In vivo spectrophotometric evaluation of neoplastic and non-neoplastic skin
      pigmented lesions. III. CCD camera-based reflectance imaging.
AB  - Reflectance spectroscopy, which allows an objective evaluation of the color of
      surfaces, has recently been proposed as a useful tool to discriminate cutaneous
      melanoma from other pigmented cutaneous lesions. A novel spectrophotometric
      system based on the use of a charge coupled device camera provided with a set of
      interference filters has been developed to acquire images of cutaneous pigmented
      lesions at selected wavelengths ranging from 420 to 1040 nm. For each filter, an
      image was captured, digitized by a frame grabber and stored in a personal
      computer to perform off-line data handling. Reflectance images were acquired of
      22 cutaneous pigmented lesions including melanoma and dysplastic, compound and
      junctional nevus. From each spectral image, three parameters, i.e. mean
      reflectance, variegation index and lesion area; were derived at the corresponding
      wavelength. The wavelength dependence of the three parameters was significantly
      different when melanoma was compared to the other investigated lesions. Although
      preliminary, our results suggest that telespectrophotometry gives useful
      information and could be utilized as an aid in the clinical diagnosis of
      cutaneous pigmented lesions.

PMID- 7638260
TI  - Molecular mechanism of drug photosensitization. 7. Photocleavage of DNA
      sensitized by suprofen.
AB  - Ultraviolet-A irradiation of a suprofen (2-[4-2(2-thenoyl) phenyl]propionic acid)
      (SPF) buffered solution (pH 7.4) in the presence of supercoiled pBR322 DNA leads
      to single strand breaks with the formation of an open circular form and
      subsequent linearization of the plasmid. On the basis of agarose gel
      electrophoresis data of samples irradiated in an air-saturated solution or in an
      oxygen-modified atmosphere, and the effects of sodium azide, D20, mannitol,
      copper(II), superoxide dismutase, 2-H-propanol, deferoxamine and surfactants, we
      suggest a photosensitization mechanism involving singlet oxygen and free
      radicals. The higher rate of photocleavage in nitrogen compared to that in an air
      saturated solution and the results obtained from oxygen consumption measurements
      support the hypothesis that both the type I and type II photosensitization
      mechanisms are operative and that oxygen quenches the excited state of the
      irradiated drug. The photosensitization model applied was in agreement with that
      previously applied to cell membrane SPF photoinduced damage. Interaction of the
      drug with DNA, studied through circular dichroism and fluorescence anisotropy,
      probably occurs through a surface binding mode. The experimental techniques used
      for assessing the photodamaging activity of this drug may be useful for screening
      of phototoxic compounds in the environment and for determining the active species
      involved.

PMID- 7638261
TI  - Photofrin accumulation in malignant and host cell populations of a murine
      fibrosarcoma.
AB  - Photofrin (25 mg/kg) was administered to the FsaR fibrosarcoma-bearing mice
      (either syngeneic or severe combined immunodeficient [SCID]) and the tumors were
      excised 24 h later. The photosensitizer content in the cells dissociated from
      tumor tissue was analyzed using flow cytometry. Staining the cell suspensions
      with the monoclonal antibodies against specific membrane markers served to
      identify the malignant cells and various types of host immune cells infiltrating
      the tumor. Photofrin content was also examined in the cells from normal tissues
      of the tumor-bearing mice (spleen, heart muscle, peritoneal macrophages). The
      results show a marked heterogeneity in the Photofrin cellular content of FsaR
      tumor, particularly within the population of tumor-associated macrophages (TAM).
      The Photofrin levels in some TAM were lower or similar to those in the malignant
      cells. In contrast, a subpopulation of TAM accumulated very high levels of the
      photosensitizer, which exceeded by far the levels found in the other tumor cell
      populations. This TAM fraction was characterized by particularly high expression
      of interleukin-2 receptors and increased cell size and granularity when compared
      to the other TAM, which suggests that these macrophages are in the activated
      state. Their average Photofrin content was almost 13 times higher than in the
      malignant cells. The lowest photosensitizer levels in the tumor were found in
      tumor-infiltrating leukocytes other than TAM. In FsaR tumors growing in SCID
      mice, the pattern of Photofrin distribution in TAM and other cellular populations
      was similar to that found in tumors growing in syngeneic mice.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7638262
TI  - Targeting activated lymphocytes with photodynamic therapy: susceptibility of
      mitogen-stimulated splenic lymphocytes to benzoporphyrin derivative (BPD)
      photosensitization.
AB  - Benzoporphyrin derivative monoacid ring A (BPD), a hydrophobic chlorin-like
      porphyrin derivative, which fluoresces strongly at 690 nm, may have potential for
      both oncologic and nononcologic applications in photodynamic therapy (PDT). To
      study the influence of cellular characteristics on the uptake of BPD, the murine
      tumor cell line (P815), and in vitro and in vivo concanavalin A (Con A) 
      stimulated and unstimulated murine splenic lymphocytes were incubated with 2
      micrograms/mL BPD at 37 degrees C for 0-60 min. At various times, cells were
      lysed and the amount of BPD taken up by cells was quantified by fluorescence
      measurements. The subsets of cells taking up BPD were analyzed using a panel of
      monoclonal antibodies and the Coulter XL fluorescence-activated cell sorter.
      Furthermore, Con A-stimulated and unstimulated spleen cells were incubated with 0
      50 ng/mliter of BPD for 1 h prior to exposure to red light (7.2 J/cm2). Cell
      survival 24 h post-PDT was measured by the MTT assay. We found that the rapidly
      dividing tumor cell line and mitogen-stimulated murine T cells (mainly CD4+/IL
      2R+) took up significantly more BPD (5-10-fold) than do unstimulated splenic
      lymphocytes. Increased BPD uptake correlated with greater photoinactivation when
      these cells were exposed to light at a wavelength of 690 nm. These findings
      suggest that activated cells of the immune system may be a target for
      photoinactivation by BPD.

PMID- 7638263
TI  - Hydrogen peroxide mediates UV-induced impairment of antigen presentation in a
      murine epidermal-derived dendritic cell line.
AB  - Ultraviolet-B (290-320 nm) radiation is known to impair the antigen-presenting
      cell (APC) function of Langerhans cells (LC), skin-specific members of the
      dendritic cell (DC) family. We sought to address mechanisms of this effect,
      focusing on the role played by hydrogen peroxide. For this purpose, we used a
      newly established murine DC line, XS52, which resembles epidermal LC in several
      respects. The APC capacity of XS52 cells, using two different CD4+ T cell clones
      as responders, was inhibited significantly (> 50%) by exposure to UV radiation
      (unfiltered FS20 sunlamps) at relatively small fluences (50-100 J/m2).
      Ultraviolet radiation also inhibited growth factor-dependent proliferation of
      XS52 cells. On the other hand, cell surface phenotype was relatively well
      preserved after irradiation; expression levels of B7-1 and B7-2 were reduced
      slightly, while other molecules (e.g. Ia, CD54, CD11a and CD18) were not
      affected. With respect to the role played by hydrogen peroxide, pretreatment with
      purified catalase (900 U/ mL) prevented UV-induced inhibition of APC function.
      Short-term exposure to 3 mM H2O2 or t-butyl H2O2 mimicked UV radiation by
      inhibiting APC function. Finally, intrinsic catalase activity was substantially
      lower in XS52 cells compared with Pam 212 keratinocytes. These results indicate
      that the generation of hydrogen peroxide alone is sufficient to produce some, but
      not all, of the deleterious effects of UV radiation on DC derived from the skin.

PMID- 7638264
TI  - Sulfophthalocyanines for photodynamic inactivation of viruses in blood products:
      effect of structural modifications.
AB  - Transmission of infectious disease through blood transfusions is well known.
      Ultraviolet irradiation, solvents, and detergents provide a means of sterilizing
      noncellular blood components. However, these harsh methods are not applicable to
      cellular blood products. Recently, attempts have been made to sterilize
      biological fluids using photodynamic treatment and phthalocyanine (Pc) dyes have
      been advanced as photosensitizers for this purpose. We have evaluated a series of
      water-soluble Pc, chelated with different central metal ions, substituted to
      different degrees with sulfonato and t-butyl groups, for their effectiveness to
      reduce virus infectivity in red blood cell suspensions. Vaccinia virus
      cytopathogenicity was determined by endpoint serial dilutions in the CV-1 cell
      line. Anti-viral activity increased with the central metal ion in the following:
      Ga(III) < Al(III) < Zn(II), and varied inversely with the degree of sulfonation.
      Furthermore, addition of a t-butyl group onto the trisulfonated dyes (PcS3[t-Bu])
      resulted in a 5-40-fold increase in anti-viral potency, suggesting that
      amphiphilicity enhances the photodynamic activity of the dye. Strong anti-viral
      photosensitizing properties cannot be the sole selection criterion. Of equal
      importance is the preservation of blood component integrity. Accordingly, the
      photohemolytic activity of the dyes was evaluated using the rate of hemolysis as
      a parameter and a toxicity index was defined. Among the most active dyes, the
      AlPcS3(t-Bu) complex exhibited the most favorable anti-viral properties combined
      with a low toxicity index. Our results suggest that trisulfophthalocyanines,
      bearing an additional t-butyl group to enhance amphiphilicity, are particularly
      promising dyes for photodynamic blood sterilization.

PMID- 7638265
TI  - Additional evidence for blepharismin photoreceptor pigment mediating step-up
      photophobic response of unicellular organism, Blepharisma.
AB  - In the ciliated protozoan, Blepharisma japonicum, the pink-colored pigment
      (blepharismin) contained in the pigment granules is believed to be the
      photoreceptor pigment responsible for the step-up photophobic response. When the
      cells partially bleached by extrusion of the pigment granules caused by cold
      shock were subsequently cultured under illuminated conditions, the pigment-less
      granules regenerated and the cells were further bleached (pigment content below
      0.5%). The photosensitivity of such colorless cells disappeared completely. In
      contrast, the blepharismin pigment regenerated gradually when such colorless
      cells were transferred to darkness. The photosensitivity of the cells also
      recovered with regeneration of the pigment. We found that blepharismin pigment
      was not photobleached in the absence of O2. The step-up photophobic response was
      also completely repressed in the absence of O2. These results strongly confirm
      that blepharismin is a photoreceptor pigment mediating photobehavior of
      Blepharisma and that O2 is required for the early step in the phototransduction
      of the light-excited pigment.

PMID- 7638266
TI  - A simple and improved method of isolation and purification for native oat
      phytochrome.
AB  - A simple procedure for the isolation and purification of 124 kDa phytochrome
      (phyA) form etiolated Avena seedlings has been developed employing ammonium
      sulfate back-extraction. After solubilization of the ammonium sulfate precipitate
      (250 g/L) an additional ammonium sulfate fractionation with 17 g per 100 mL
      rather than column chromatography was performed. After several steps of the
      "washing-out" procedure with 100 mM phosphate buffer, phytochrome was solubilized
      in 10 mM phosphate buffer. The resulting phytochrome had a specific absorbance
      ratio (SAR = A666/ A280) ranging from 0.60 to 0.85. These values are equivalent
      to those of phytochrome preparations after hydroxylapatite chromatography
      ammonium sulfate back-extraction. The total isolation-purification time was 8 h
      and yield of the chromoprotein was 50% higher than the yield using conventional
      techniques. The phytochrome preparation, after application to a Toyopearl HW-65S
      gel filtration column, produced very pure 124 kDa phyA with a specific absorbance
      ratio greater than 1.00. The spectral characteristics are identical to those
      described for the best of the highly purified native chromoprotein preparations.

PMID- 7638267
TI  - Spectroscopic and photoacoustic studies of hypericin embedded in liposomes as a
      photoreceptor model.
AB  - In photoresponsive ciliates, like Blepharisma japonicum and Stentor coeruleus,
      the photoreceptor pigments responsible for photomotile reactions are hypericin
      type chromophores packed in highly osmiophilic subpellicular granules. Lipopsomes
      loaded with hypericin can constitute a simple model system, appropriate for
      understanding the primary light-induced molecular events triggering the sensory
      chain in these microorganisms. Optical absorption, steady-state and time-resolved
      fluorescence and pulsed photoacoustic calorimetry have been used to measure
      spectral distributions, fluorescence lifetimes, radiative and radiationless
      transition quantum yields of hypericin when assembled into egg L-alpha
      phosphatidylcholine liposomes. With respect to hypericin ethanol solutions, both
      absorption and fluorescence maxima are 5 nm red shifted when the pigment is
      inserted into the lipidic microenvironment, regardless of the hypericin local
      concentration. Increasing by 100 times the hypericin local concentration
      decreases the relative fluorescence quantum yield by a factor of around 150 and
      the fraction of thermally released energy, conversely, increases from 0.6 to 0.9.
      From the analysis of fluorescence lifetimes and their relative amplitudes it
      appears that a subnanosecond living component is predominant at the highest
      hypericin local concentrations.

PMID- 7638268
TI  - Magnetic field effects on the photohemolysis of human erythrocytes by ketoprofen
      and protoporphyrin IX.
AB  - Application of a static magnetic field (3350 G) during UV-irradiation (> 300 nm)
      reduced the time for 50% photohemolysis of human erythrocytes by the phototoxic
      drug ketoprofen (3-benzoyl-alpha-methylbenzoacetic acid) from 96 min to 78 min.
      This observation can be attributed to a magnetic field induced decrease in the
      rate of intersystem crossing (kISC) of the geminate triplet radical pair
      generated by the reduction of ketoprofen in its triplet excited state by
      erythrocyte membrane constituents, probably lipids. The decrease in kISC results
      in an increase in the concentration and/or lifetime of free radicals that escape
      from the triplet radical pair. Thus the critical radical concentration needed to
      cause membrane damage cell lysis is reached sooner in the presence of the
      magnetic field. In contrast, the photohemolysis induced by the photodynamic agent
      protoporphyrin IX was not affected by the magnetic field. Protoporphyrin IX
      photohemolysis, which is initiated by singlet oxygen, does not involve the
      initial generation of a triplet radical pair and so is not influenced by the
      magnetic field. The example of a magnetic field effect on a toxicological process
      involving free radicals.

PMID- 7638269
TI  - Liposome fusion and lipid exchange on ultraviolet irradiation of liposomes
      containing a photochromic phospholipid.
AB  - A photochromic phospholipid, 1,2-bis[4-4(4-n-butylphenylazo) phenylbutyroyl]
      phosphatidylcholine (Bis-Azo PC) has been incorporated into liposomes of gel- and
      liquid-crystalline- phase phospholipids. Liposomes of gel-phase phospholipid are
      stable in the presence of the trans photostationary state Bis-Azo PC and can
      encapsulate fluorescent marker dye. On photoisomerization to the cis
      photostationary state, trapped marker is rapidly released. Liposomes containing
      Bis-Azo PC can rapidly fuse together after UV isomerization, this process
      continuing in the dark. Exposure to white light causes reversion of Bis-Azo Pc to
      the trans form and halts dye leakage and vesicle fusion. Both unilamellar and
      multilamellar liposomes are able to fuse together on UV exposure. On UV
      photolysis, liposomes containing Bis-Azo PC do not fuse with a large excess of
      unlabeled liposomes, but transfer of Bis-Azo PC can be demonstrated
      spectrophotometrically. Vesicles of pure gel-phase lipid containing trapped
      marker dye but initially no Bis-Azo PC become leaky as a result of this lipid
      transfer. Liposomes composed of liquid-crystalline-phase phosphatidylcholine-
      containing Bis-Azo PC neither leak trapped marker no fuse together on photolysis,
      nor do liquid-crystalline-phase liposomes fuse with gel-phase liposomes under
      these conditions. These results are discussed together with some possible
      applications of liposome photodestabilization.

PMID- 7638270
TI  - Interaction between human alpha1-acid glycoprotein (orosomucoid) and 2-p
      toluidinylnaphthalene-6-sulfonate.
AB  - The interaction between human alpha1-acid glycoprotein (orosomucoid) and the
      fluorescent probe, 2-p-toluidinylnaphthalene-6-sulfonate (TNS) has been studied.
      An association constant of 16.7 (+/- 3) x 10(3) M-1 was obtained for the complex
      at 20 degrees C with a stoichiometry of 1:1. From the effect of temperature on
      the binding process, the standard enthalpy change for the binding is calculated
      to be delta H0 = -18 +/- 3 kJ mol-1 and the standard entropy change delta S0 = 19
      +/- 12 J K-1 mol-1. The tryptophan fluorescence of the protein can be described
      by a sum of three exponentials. Upon TNS binding, the average fluorescence
      lifetime of the protein in the complex changes much less than the fluorescence
      intensity. The bound TNS is therefore a very efficient acceptor for the protein
      fluorescence. The TNS bound to orosomucoid present two fluorescence lifetimes 11
      and 4.3 ns. The possible origins of the two lifetimes are discussed.

PMID- 7638271
TI  - Contrasting structural impacts induced by cis-syn cyclobutane dimer and (6-4)
      adduct in DNA duplex decamers: implication in mutagenesis and repair activity.
AB  - The relative biological importance of cis--syn cyclobutane dimer and pyrimidine(6
      4)pyrimidone photoadduct ([6-4] photoadduct) appears to be dependent on the
      biological species, dipyrimidine sites and local conformational variation induced
      at the damaged sites. The single-strained deoxynucleotide 10-mers containing the
      site-specific (6-4) adduct or cis--syn cyclobutane dimer of thymidylyl(3'-->5')
      thymidine were generated by direct photolysis of d(CGCATTACGC) with UVC (220-260
      nm) irradiation or UVB (260-320 nm) photosensitization. Three-dimensional
      structures of the duplex cis--syn and (6-4) decamers of
      d(CGCATTACGC)xd(GCGTAATGCG) were determined by NMR spectroscopy and the
      relaxation matrix refinement method. The NMR data and structural calculations
      establish that Watson-Crick base pairing is still intact at the cis--syn dimer
      site while the hydrogen bonding is absent at the 3'-side of the (6-4) lesion
      where the T-->C transition mutation is predominantly targeted. Overall
      conformation of the duplex cis--syn decamer was B-DNA and produced a 9 degree
      bending in the DNA helix, but a distinctive base orientation of the (6-4) lesion
      provided a structural basis leading to 44 degree helical bending. The observed
      local structure and conformational rigidity at the (6-4) adduct of the
      thymidylyl(3'-5')-thymidine (T-T [6-4]) lesion site suggest the potential absence
      of hydrogen bonding at the 3' sides of the (6-4) lesion with a substituted
      nucleotide during replication under SOS conditions. Contrasting structural
      distortions induced ny the T-T (6-4) adduct with respect to the T-T cis--syn
      cyclobutane pyrimidine photodimer may explain the large differences in mutation
      spectrum and repair activities between them.

PMID- 7638272
TI  - The use of lipid headgroup charge to enhance photoinduced electron transfer in
      vesicles: reactions of functionalized pyrene with a two component viologen
      system.
AB  - Kinetics of photoinduced electron transfer from a lipid functionalized pyrene, 1
      (10-(6(8)-octadecylpyrenyl) decanoyl)-2-hexanoyl-sn-glycero-3-phosphorycholine
      (OPyPC), to a two component viologen acceptor system have been measured by laser
      flash photolysis. N,N'-tetramethylene-2,2' -bipyridinium ion (DQ2+) and N,N'
      dipropyl-4,4'-bipyridinium sulfonate (PVS), have been utilized as the primary and
      secondary acceptors. It has been shown that utilization of a lipid with a net
      negatively charged phosphatidylglycerol headgroup provides a driving force for
      localizing high concentrations of primary acceptor (DQ2+) in the region of donor.
      Subsequently, the charged interface can act to maintain long-term separation
      between the oxidized pyrene donor (OPyPC+) and the reduced secondary acceptor,
      PVS-. When a dioleoyl lipid is used, reaction of (OPypc+) with the double bond
      competes significantly with back reaction. However, substitution of
      diphytylphosphatidylglycerol for the dioleoyl analog results in a cation lifetime
      of about 0.5 ms and a continued very long-lived reduced species (approximately 4
      h). Quantum yields of approximately 0.15 may be obtained in this system.

PMID- 7638273
TI  - Decay kinetics of N,N,N',N'-tetramethylbenzidine photocations in frozen micellar
      solution of cetyltrimethylammonium bromide.
AB  - After UV irradiation of rapidly frozen solutions of N,N,N',N'
      tetramethylbenzidine (TMB) in dilute aqueous micellar cetyltrimethylammonium
      bromide at 80 K, the ESR signal corresponding to the TMB+ cation was detected
      indicating photoionization. This signal was monitored as a function of time at
      various temperatures between 80 K and 260 K. On a timescale of a few days the
      signal decayed to a plateau value that was stable for months. Two distinct second
      order processes for the decay from the initial to the plateau value were
      observed: one prevailing at low temperatures with an activation energy of 0.6
      kJ/mol, and one prevailing at T > 220 K with an activation energy of 13 kJ/mol.
      By means of spin probe investigations the latter process was shown to be
      connected with a local softening of the region adjacent to the micellar surface.

PMID- 7638274
TI  - The generation of hydrogen peroxide by the UVA irradiation of human lens
      proteins.
AB  - The water-insoluble proteins from aged human lens are known to contain protein
      bound chromophores that act as UVA senisitizers. The irradiation of a sonication
      solubilized, water-insoluble fraction from human lenses (55-75 years) with UVA
      light (1.5 kJ/cm2, gamma > 338nm) caused an oxygen-dependent photolysis of
      tryptophan, not seen when either alpha-crystallin or lysozyme were irradiated.
      The suggested requirement for active oxygen species was consistent with a linear
      increase in hydrogen peroxide formation, which was also observed. A final
      concentration of 55 microM H2O2 was attained, with no H2O2 being detected in
      either dark-incubated controls or in irradiated samples of native proteins. The
      UVA-dependent H2O2 formation was increased 50% by superoxide dismutase (SOD) and
      abolished by catalase, arguing for the initial generation of superoxide anion. A
      linear photolysis of histidine and tryptophan was also seen; however, the
      addition of SOD or SOD and catalase had no effect on the photolytic destruction
      of either amino acid. Superoxide dismutase increased the oxidation of protein SH
      groups implicating H2O2, but SOD and catalase caused a decrease in SH oxidation
      only at later time periods. The direct addition of H2O2 to a water-insoluble
      sonicate supernatant fraction caused only a slight oxidation of SH groups, but
      this was increased four- to eight-fold when the protein was denatured in 4.0 M
      guanidine hydrochloride. Overall, the data suggest a UVA-dependent oxidation of
      protein SH groups via H2O2 generated within the large protein aggregates of the
      water-insoluble fraction. These data also provide a mechanism for oxidation of
      the sulfur-containing amino acids in vivo--a process that is known to accompany
      the formation of age-onset cataracts.

PMID- 7638275
TI  - The development of personal dosimeters for use in the visible and ultraviolet
      wavelengths regions. The Salisbury Eye Evaluation Team.
AB  - We have designed, developed, and field evaluated a two-part personal dosimeter
      for estimating ocular exposure to visible and ultraviolet radiation. The detector
      head id compact enough to be mounted on the bow of eyeglass frames, and the
      recorder is small enough to be carried in a shirt pocket. The detector head
      consists of a silicon photodiode with filter (Schott glass GG400) and diffuser
      for visible light measurements and a polysulphone film badge for ultraviolet-B
      (UVB, 290-320 nm) measurements. The measurements correspond well to those
      obtained using ambient monitors and should be useful for studies of ocular UVB
      exposure.

PMID- 7638276
TI  - Silicone implants and the inhibition of cancer.
AB  - The safety of augmentation mammaplasty and its relationship to breast cancer has
      been a much debated topic. The authors previously showed a decreased incidence of
      breast cancer in rats who had received silicone implants 2 weeks before
      carcinogen stimulation. The present study was designed to determine (1) whether
      this protective effect is influenced by the location of the implant, and (2)
      whether tumor incidence could also be altered in spontaneous mammary tumor
      forming animals, the C3H/OuJ mice. (1) A total of 110 rats received either a
      silicone implant or a sham operation in one of three locations: inframammary
      region, dorsum, or intraperitoneal cavity. Methylnitrosoured (MNU) injections
      occurred 14 days after implantation. Animals were examined weekly for tumor
      growth and were killed 250 days after MNU injection. Animals with silicone
      implants beneath the mammary gland had a statistically significant lower
      incidence of breast cancer formation (11.5 percent) compared with both dorsally
      implanted animals (45.8 percent) and sham controls (64 percent). (2) Sixty
      C3H/OuJ mice underwent implantation of either a silicone implant, free silicone
      gel, silicone sheet, or a sham operation. At 50 weeks of age, after weekly
      examinations, the animals were killed. The cancer incidence in mice with silicone
      implants was 17 percent compared with 50 percent found in sham controls. Exposure
      to a silicone prosthesis at an early age does not seem to increase tumor
      incidence and may even have a locally protective effect against breast cancer
      formation.

PMID- 7638277
TI  - The image of plastic surgeons in news media coverage of the silicone breast
      implant controversy.
AB  - We analyzed the portrayal of plastic surgeons in the media by using the
      qualitative method of narrative analysis of newspaper articles available between
      July 1991 and June 1992 and popular magazine articles available from 1965 through
      1992 in the Tampa Bay area. Plastic surgeons were presented as antagonists in the
      "horror stories" of sick women, as combatants in a medical community divided in
      its assessment of health risks, and as profit-oriented businesspersons. Patients
      were fully developed heroines, whereas plastic surgeons were described negatively
      by their antagonists, which undermines the expertise, good character, and good
      will that determine credibility for plastic surgeons. Providing the press with
      stories about their own efforts to help patients might have helped plastic
      surgeons receive more favorable press and enhance their credibility. More
      sophisticated handling of underlying values and the problem of communicating
      safety also might have been helpful.

PMID- 7638278
TI  - Crouzon and Apert syndromes: intracranial volume measurements before and after
      cranio-orbital reshaping in childhood.
AB  - This study applied a proven method for obtaining intracranial volume (ICV)
      measurements using computed tomographic scans to document ICVs in children with
      Crouzon and Apert syndrome before and after cranio-orbital reshaping procedures.
      Their ICV also was compared with those of an age- and gender-matched cohort and
      reviewed their rate of cranial expansion. The study included 21 children who
      presented sequentially with Crouzon (n = 13) or Apert (n = 8) syndrome between
      1987 and 1991 and who subsequently underwent a standard first-stage cranio
      orbital reconstruction by the senior author (J.C.P.) in conjunction with a
      pediatric neurosurgeon. The primary method of osteotomy and bone graft fixation
      varied (i.e., wires, microplates, miniplates, and screws). The series included 16
      females and 5 males with an average age at the time of operation of 13 months
      (range, 6 to 46 months). The postoperative clinical follow-up ranged from 12 to
      60 months at the time of the study's completion. Comparison of the IVCs of the
      Apert patients preoperatively and postoperative with age and gender control
      volumes showed that six of eight had volumes at least 2 SD above the mean.
      Postoperatively, the trend continued with all eight patients followed
      longitudinally; all maintained volumes in excess of 2 standard deviations above
      the mean. Preoperatively, for the Crouzon children evaluated, 12 of 13 had ICV
      values greater than the mean. When comparing the patients' postoperative volumes
      to the normative data, all 13 maintained values at or greater than the mean at
      the time of their postoperative determination. Ten of the 13 achieved ICVs at or
      greater than 2 SD above the mean. When reviewing each Crouzon patient's cranial
      capacity over time, 5 of the 13 approximated the normal growth curve whereas 6 of
      the 13 exceeded it. This study confirms that Apert patients are macrocephalic
      before and after standard cranio-orbital procedures carried out in childhood. For
      the majority of children born with Crouzon syndrome, the cranial capacity will
      exceed the mean early in life and expand at a rapid rate after cranio-orbital
      decompression. The biologic explanation for these findings remain unclear.

PMID- 7638279
TI  - A long-term appraisal of the unilateral complete cleft lip repair: one surgeon's
      experience.
AB  - The authors reviewed 85 patients with unilateral complete cleft lip repaired with
      a low triangular flap technique. Clefts were classified into four categories,
      depending on the degree of deformity. The clinical results, as evidenced in
      standardized slides, were assessed by a professional panel using a weighted
      formula adapted from that devised by Williams. The Farkas-Lindsay anthropometric
      technique was also used to measure all dimensions of the lip and nose, with the
      results calculated as a ratio of the cleft to normal side. The findings
      demonstrated that the method of classification was consistent and reliable. As
      expected, the panel gave the postoperative results of the Simonart's and mild
      degree clefts the highest ratings, with the severe clefts having the lowest. The
      consultant surgeons awarded the highest marks and the clinical fellows, the
      lowest. The residual nasal deformity continues to be the challenge rather than
      the lip defect, as evidenced by an average of 1.7 revisionary procedures on the
      nose compared with 0.7 on the lip. A combination of subjective and objective
      methods of evaluation has been incorporated into a critical clinical review of
      these patients.

PMID- 7638280
TI  - A study of the supraorbital nerve.
AB  - A detailed description of the anatomical relationships of the supraorbital nerve
      as it courses across the forehead and under the scalp cannot be found in most
      anatomy textbooks, and illustrations of the nerve beyond the superior orbital rim
      frequently misrepresent its course. Because the supraorbital nerve is a structure
      at risk in many plastic surgical techniques, the plastic surgeon would benefit
      from a clearer understanding of its anatomy and function. The supraorbital nerve
      was studied anatomically in 12 (24 half-head) fresh cadaver specimens, and its
      sensory distribution was studied in 30 living subjects using selective nerve
      blocks. Beyond the orbital rim, the supraorbital nerve has two consistently
      present divisions: (1) a superficial (medial) division that passes over the
      frontalis muscle, providing sensory supply to the forehead skin and only to the
      anterior margin of the scalp in 90 percent of the study subjects; and (2) a deep
      (lateral) division that runs cephalad across the lateral forehead between the
      galea aponeurotica and the pericranium as the sensory nerve to the frontoparietal
      scalp. When a forehead lift is performed, injury to this deep division causes
      most of the distressful sequelae of scalp numbness and paresthesia. Unlike the
      superficial division, the course of the deep division in all cadaver specimens
      and its sensory distribution in all living volunteer subjects was consistent.
      This study has application for any procedure requiring scalp or forehead
      incisions, such as the forehead lift and the endoscopic facial
      techniques.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7638281
TI  - Comparison of rigid plate versus wire fixation in the management of zygoma
      fractures: a long-term follow-up clinical study.
AB  - We evaluated retrospectively 101 patients to assess clinically the results of
      fixation methods on isolated unilateral zygoma fractures (mean follow-up 3.2
      years). All patients were examined by an investigator who was blinded to the
      initial fixation method. Ninety-two patients were treated with wire or plate
      fixation alone. The major clinical parameters assessed were globe position
      abnormalities (enophthalmus and dystopia), malar projection, and cheek sensation.
      Rigid plate fixation achieved statistically better long-term malar symmetry (p =
      0.002) and approached statistical significance in the achievement of more normal
      globe position (p = 0.06) compared with wire fixation alone. Cheek sensation
      showed a nonsignificant trend (p = 0.13) toward improvement with plate fixation.
      Other parameters that were evaluated were anatomic location of fixation points,
      number of fixation points, surgical approach and exposure, and breakdown of
      fixation dates by specialty. None of these factors showed any significant
      influence on outcome. The present study confirms what we have known to be true
      from our clinical experience--that rigid internal fixation is superior in
      minimizing or preventing long-term sequelae of facial fractures.

PMID- 7638282
TI  - Reverse temporalis muscle flap: treatment of large anterior cranial base defect
      with direct intracranial-nasopharyngeal communication.
AB  - Inadequately managed frontal sinus fracture or sinusitis can pose a major problem
      of intracranial-nasopharyngeal communication. Life-threatening ascending
      infection of the intracranium is inevitable unless the intracranium is separated
      from the nasopharynx. In five patients with frontal bone defect associated with
      direct intracranial-nasopharyngeal communication, the authors used reverse
      temporalis muscle flap based on the superficial temporal vessels to obliterate
      the nasocranial communication. With the authors' method, the nasocranial
      communication were sealed off permanently, and the ascending infection from
      intracranial-nasopharyngeal communication was controlled successfully. The
      reverse temporalis muscle flap, which survives by reversed arterial flow through
      the vascular connection, exists between the superficial temporal artery and the
      deep temporal artery in the region of temporalis muscle origin. The reverse
      temporalis muscle flap is versatile and is recommended especially when other
      local flaps are not available to obliterate the nasocranial communication.

PMID- 7638283
TI  - A review of 60 consecutive fibula free flap mandible reconstructions.
AB  - Sixty consecutive fibula free flap mandible reconstructions were performed for
      oncologic defects. Patient age averaged 46.7 years. Eighty-one percent were
      primary reconstructions. Sixty-two percent were lateral defects; 22 percent were
      anterior; and the remainder had combined defects. The bone gap averaged 9.4 cm. A
      skin island was included with the fibula in 85 percent of patients but was
      actually needed in only 62 percent. Miniplate fixation was used in 96 percent.
      Templates derived from radiographic studies were used as an aid in shaping the
      fibula. Average anesthesia time was 14.54 hours; the transfusion requirement, 3
      units; and hospitalization, 22 days. Fifty-nine flaps were successfully
      transferred. Ninety percent of skin islands raised were completely viable.
      Average postoperative interincisal opening was 35.2 mm. Osseointegrated implants
      were placed in 56 percent of suitable candidates, and all implants integrated
      into bone. Aesthetic results were usually good when the soft tissue defect was
      limited, but poor when it was extensive. Donor site morbidity was usually mild
      and transient. The most significant problem was delayed healing in patients
      closed with a skin graft. Postoperatively, all patients ambulated normally, and
      none used assist devices. Reoperation for donor site problems was rare. The
      fibula has many assets that together make it an ideal choice for the
      reconstruction of most mandible defects. The skin island is usually reliable if
      it is designed and raised properly. Donor site morbidity is largely
      inconsequential. The primary contraindication to the use of the fibula for
      mandible reconstruction is severe peripheral vascular disease.

PMID- 7638284
TI  - High-lateral-tension abdominoplasty with superficial fascial system suspension.
AB  - Modern abdominoplasty techniques were developed in the 1960s. The advent of
      liposuction has reduced the need for classic abdominoplasty and allowed more
      aesthetic sculpting of the entire trunk. However, the combination of significant
      truncal liposuction and classic abdominoplasty is not recommended due to the
      increased risk of complications. Although the surgical principles of classic
      abdominoplasty certainly have stood the test of time, they are based on two
      theoretical assumptions that may be proved to be inaccurate. The first assumption
      is that wide direct undermining to costal margins is essential for abdominal flap
      advancement. In fact, discontinuous undermining allows effective loosening of the
      abdominal flap while preserving vascular perforators. The second inaccurate
      assumption is that with aging and weight fluctuations (including pregnancy),
      abdominal skin relaxation occurs primarily in the vertical direction from the
      xiphoid to the pubis. This is true in the lower abdomen, but in most patients a
      strong superficial fascial system adherence to the linea alba in the epigastrium
      limits vertical descent. Epigastric laxity frequently results from a progressive
      horizontal loosening due to relaxation of the tissue along the lateral trunk.
      Experience with the lower-body lift procedure has shown that significant lateral
      truncal skin resection results in epigastric tightening. In these patients, the
      ideal abdominoplasty pattern would resect as much or more laterally than
      centrally, leading to more natural abdominal contours. Fifty patients who
      underwent high-lateral-tension abdominoplasty with and without significant
      truncal liposuction and other aesthetic procedures were followed for 4 to 16
      months. The primary indication for surgery was moderate to severe laxity of
      abdominal skin and muscle with or without truncal fat deposits. Complication
      rates were equal to or less than those of historical controls and did not
      increase with significant adjunctive liposuction. The key technical elements of
      this procedure include direct undermining limited to the paramedian area,
      discontinuous undermining to costal margins and flanks as needed, skin resection
      pattern with significant lateral resection and highest-tension wound closure
      placed laterally, superficial fascial system repair with permanent sutures along
      the entire incision, and liberal use of adjunctive liposuction in the upper
      abdomen and the lateral and posterior trunk.

PMID- 7638285
TI  - Abdominal wall strength, bulging, and hernia after TRAM flap breast
      reconstruction.
AB  - The incidence of postoperative abdominal bulge, hernia, and the ability to do sit
      ups was reviewed in a series of 268 patients who had undergone free TRAM (FTRAM)
      or conventional TRAM (CTRAM) flap breast reconstruction. Minimum follow-up was 6
      months. Patients were divided into four groups: unilateral FTRAM (FT1P; n = 123),
      double-pedicle bilateral FTRAM (FT2P; n = 45), single-pedicle CTRAM (CT1P; n =
      40), and double-pedicle or bilateral CTRAM (CT2P; n = 60). The incidence of
      abdominal bulges (3.8 percent) and hernia (2.6 percent) was similar in the four
      groups. Synthetic mesh, however, was required for reinforcement of donor site
      closure twice as often in the CTRAM patients. The ability to perform sit-ups was
      greatest in the FT1P group (63.0 percent), slightly lower in the CT1P group (57.1
      percent), still lower in the FT2P group (46.2 percent), and lowest in the CT2P
      group (27.1 percent; p = 0.0005). Patients reconstructed with an FTRAM flap were
      more likely to be able to do sit-ups (58.3 percent) than were those reconstructed
      with a CTRAM flap (38.2 percent; p = 0.0074). Patients who had only one muscle
      pedicle used were more likely to be able to do sit-ups (61.7 percent) than were
      those who had two muscle pedicles used (35.6 percent; p = 0.0003). We conclude
      that the incidence of abdominal bulge or hernia is relatively independent of the
      type of TRAM flap used and the number of muscle pedicles harvested. On the other
      hand, postoperative abdominal strength, as measured by the ability do sit-ups, is
      influenced significantly by both of these factors.

PMID- 7638286
TI  - Incidence of calcifications in the breast after surgical reduction and
      liposuction.
AB  - Liposuction of the breast in combination with vertical mammaplasty was applied to
      250 breasts among 386 reductions of large breasts performed in 2 years (1989 to
      1991). To evaluate the possible damage to the breast caused by this combined
      procedure, especially in terms of the occurrence of the postoperative development
      of calcifications, a comparative study of preoperative and postoperative
      mammograms was undertaken in 60 randomly selected cases (120 breasts), 34 with
      and 26 without liposuction. Altogether, 13 calcifications (11 percent) were
      discovered during the 6- to 30-month follow-up, representing the lowest rate
      reported in the literature. Deep intraparenchymal calcifications were more
      frequent after liposuction; most (5 of 7) were macrocalcifications. None could be
      confused with malignant calcifications because they were more scattered, more
      regular, and less numerous. Attempts to evaluate the fat content of breasts via
      preoperative mammography failed to prove this examination a useful way to predict
      the viability of breast liposuction.

PMID- 7638287
TI  - PMMA microspheres (Artecoll) for skin and soft-tissue augmentation. Part II:
      Clinical investigations.
AB  - Artecoll is an injectable implant for long-lasting correction of wrinkles and
      other skin defects. Artecoll consists of fine polymethyl-methacrylate (PMMA)
      microspheres suspended 1:3 in a 3.5% collagen solution. The microspheres are
      characterized by exceptional surface smoothness, homogenicity, and purity. The
      size of the microspheres of 30-40 microns diameter is small enough to allow
      subdermal implantation using a 27-gauge needle. Phagocytosis and dislocation of
      the implant is prevented by fast encapsulation of each single microsphere with
      connective tissue. Increased scarring but no granuloma formation has been
      detected as is common with other injectable implants with irregular surfaces. The
      experience from more than 600 patients and a prospective study in 118 patients
      with 200 implantation sites were evaluated. The good early results have continued
      for 5 years. Of the patients evaluated, 89.5 percent were satisfied and would ask
      for the treatment again. The overall complication rate is very low, and prolonged
      redness or visible granules are due to implantations that are too superficial.
      Other applications in soft-tissue augmentation are discussed.

PMID- 7638288
TI  - Lower back reconstruction: an approach to wound closure in the cancer patient.
AB  - Repair of the lower back wound in the patient with cancer presents the surgeon
      with a plethora of challenges. Frequently, the wide range of the surgeon's
      armamentarium of flaps must be used to provide stable wound coverage. We present
      the reconstruction techniques used in five patients with cancer who had lower
      back wounds below T10 and of at least 100 cm2. The approach we used to evaluate
      the lower back wound and to determine surgical techniques and options for
      reconstruction is discussed.

PMID- 7638289
TI  - Free tissue failure is not an all-or-none phenomenon.
AB  - A common misconception among microsurgeons is that free tissue failure is an "all
      or-none" phenomenon. In other words, there is an instantaneous cessation of blood
      flow to a flap primarily due to thrombosis at the arterial or venous anastomotic
      site (primary thrombosis) with complete flap loss as a result. Contrary to this
      belief, we have found that free tissue transfers occasionally "die" a slow,
      progressive, and partial death. This most likely is due to gradual "shutting
      down" of the microcirculation by the showering of microemboli downstream from the
      arterial anastomosis (secondary thrombosis). We discuss our clinical experience
      during the past 6 years with 10 patients in whom free flap failure was not an all
      or-none phenomenon and describe the expectant management of these failing free
      flaps. Microvascular reconstruction of the lower extremities was performed for
      recalcitrant sickle cell ulceration, chronic venous stasis ulceration in a
      patient with anti-thrombin III deficiency, dry gangrene of the plantar surface of
      the foot and toes secondary to posterior tibial artery injection in an
      intravenous drug abuser, Gustillo type IIIc injury requiring reconstitution of
      the femoropopliteal artery after an automobile bumper injury, Gustillo type IIIb
      injury resulting from gunshot wounds, an open ankle joint in a patient with
      severe peripheral vascular disease, and osteomyelitis. Other cases included cheek
      soft tissue reconstruction after wide resection of a recurrent
      dermatofibrosarcoma protuberans of the parotid gland, chest wall coverage after
      claviculectomy for osteoradionecrosis, and thumb replantation complicated by
      refractory vasospasm. Latissimus dorsi (four patients), rectus abdominis (three
      patients), scapular (one patient), and radial forearm fasciocutaneous (one
      patient) flaps were used. Flap compromise was detected between 4 hours and 6
      weeks after surgery. Salvage attempts included Fogarty thrombectomy (four
      patients), anastomotic revision (two patients), streptokinase instillation (one
      patient), and leech application (one patient). Failing free flaps were managed
      expectantly with the use of daily dressing changes. This allowed for the survival
      of sufficient soft tissue to effect coverage of exposed bone, tendon, or joint.
      Hyperbaric oxygen was not administered. Tangenital excision of the eschar was
      performed between 6 and 51 days after free tissue transfer. Skin grafting was
      delayed for 15 to 80 days. In all cases, a successful outcome was achieved
      ultimately by either a single skin-grafting procedure (seven patients) or groin
      flap coverage (one patient). Follow-up ranged from 2 to 35 months.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7638290
TI  - Pulp plasty after toe-to-hand transplantation.
AB  - Pulp plasty is a simple procedure that is used to debulk the bulbous-appearing
      pulp of a transplanted digit after toe-to-hand transplantation. A retrospective
      review of the effect of pulp plasty on the appearance and function of the
      debulked digit was conducted of 82 digits on 51 patients. Pulp plasty was
      performed on average of 14 months after toe-to-hand transplantation; the average
      follow-up interval was 20 months. Subjective improvement in appearance and
      function was reported in 67.1 and 63.4 percent, respectively, of the debulked
      digits. Painful scarring was rare, and hypersensitivity was not reported.
      Sensation was not affected adversely by pulp plasty. The procedure was considered
      to be worthwhile in 87.8 percent of the cases. Pulp plasty is a simple and
      effective procedure after toe-to-hand transplantation that enhances the
      appearance and function of the transplanted digit. Patient satisfaction with the
      procedure is high.

PMID- 7638291
TI  - The titanium grommet in flexible implant arthroplasty of the radiocarpal joint: a
      long-term review of 44 cases.
AB  - Flexible implant arthroplasty of the radiocarpal joint has come under increasing
      criticism since its introduction in 1967. Recent long-term reviews report high
      failure and revision rates. In 1984, titanium grommets became available. By
      providing a protective interface between sharp bone edges and the flexible hinge
      device, this refinement raised hope for improved performance. This report
      provides the first long-term review of the grommet's efficacy. The overall
      success rate was 95 percent. No implant fractures were observed in the setting of
      nondisplaced grommets; however, one implant did fracture in association with
      grommet displacement. Radiographic review of cortical bone density showed an
      increase in the region of the grommet in virtually all cases. These results offer
      significant improvement over those reported for flexible implant radiocarpal
      wrist arthroplasties done without protective grommets. The results suggest a
      wider indication for implant arthroplasty of the radiocarpal joint and hold
      promise for longer-term durability.

PMID- 7638293
TI  - The hemodynamic and hematologic effects of cigarette smoking versus a nicotine
      patch.
AB  - Patients who smoke have higher complication rates than nonsmokers in the
      postoperative period. The authors designed an experimental protocol for habitual
      smokers (n = 30) to determine the specific hemodynamic and hematologic adverse
      effects possibly caused by nicotine and whether the method of nicotine delivery
      and systemic nicotine levels achieved might influence these adverse effects.
      During the 5-day study, subjects were asked to refrain from smoking, and testing
      sessions were conducted as follows: on day 1, the subjects smoked two cigarettes
      immediately before testing; on day 3 (control day), testing was done after not
      smoking for 48 hours and then the subjects were instructed to wear a transdermal
      nicotine patch (PROSTEP 22 mg/day) for 24 hours and replace it with another so
      that, on day 5, testing took place after the subjects had worn the patch for
      approximately 34 hours. At each testing session, digital artery pulse amplitude
      and a number of clinical and serum blood level parameters were measured. Relative
      digital blood flow after smoking (69.2 +/- 5.8%) and with the patch (80.4 +/-
      7.6%) was lower than on the control day (100.0 +/- 0.0%). The nicotine patch,
      unlike smoking, had no effect on vasopressin or fibrinogen concentrations,
      hematocrit, or white cell or platelet counts; both smoking and the patch resulted
      in elevated norepinephrine levels.

PMID- 7638292
TI  - Ultraviolet excitation fluorescence spectroscopy: a noninvasive method for the
      measurement of redox changes in ischemic myocutaneous flaps.
AB  - In this report, we discuss application of the noninvasive technology of
      ultraviolet fluorescence spectroscopy to the metabolic analysis of normal and
      compromised myocutaneous flaps. Acute changes in tissue redox states during
      ischemia and reperfusion were determined analysis of changes in the fluorescence
      spectrum of reduced nicotinomide adenine dinucleotide (NADH). Analysis of the
      system for NADH fluorescence showed good correlation between excitation spectra
      recorded at 450 nm from pure beta-NADH and those recorded from porcine rectus
      abdominis myocutaneous flaps. Sequential measurements of surface fluorescence
      were obtained from six flaps subjected to 6 hours of warm arterial ischemia and 4
      hours of reperfusion. Results were compared with spectra obtained from six
      contralateral nonischemic control flaps. A significant mean increase in NADH
      fluorescence (49 percent; p < 0.05) was demonstrated within 30 minutes of
      vascular occlusion. Fluorescence intensity continued to increase throughout the
      ischemic period, reaching 320.5 percent of baseline values at 6 hours.
      Reperfusion resulted in the prompt return of fluorescence intensity to baseline
      levels. These results show that fluorescence spectroscopy of endogenous NADH is a
      sensitive and reliable indicator of vascular occlusion in experimental
      myocutaneous flaps.

PMID- 7638294
TI  - Internal calvarial bone distraction in rabbits with experimental coronal suture
      immobilization: effects of overdistraction.
AB  - This study was designed to assess the effects of overdistraction of an
      experimentally immobilized coronal suture using an internal appliance on
      craniofacial growth in rabbits. Fifty-three, 1.5-week-old rabbits were used.
      Markers were placed on either side of the calvarial sutures. Thirty-nine rabbits
      had bilateral coronal suture immobilization using methyl methacrylate; 14 rabbits
      served as normal controls. At 6 weeks of age, the 39 immobilized rabbits were
      randomly assigned to four groups: (1) immobilized controls (n = 14); (2)
      suturectomy (n = 6); (3) suturectomy with distraction (n = 9); and (4)
      suturectomy with overdistraction (n = 10). Lateral head radiographs were taken at
      1.5, 6, 12, and 18 weeks of age. Results revealed that, by 18 weeks of age,
      rabbits with overdistraction exhibited significant compensatory growth
      abnormalities in the cranial vault, midface, and anterior cranial base compared
      with the other groups. Results indicate that overdistraction may contribute to
      craniofacial anomalies through altered growth vectors and compressive tension
      stress forces at adjacent sutures and suggest that it may be important to keep
      "pace" with the growing coronal suture and neurocapsular matrix during
      distraction to reestablish normal craniofacial morphology.

PMID- 7638295
TI  - Tricalcium phosphate and osteogenin: a bioactive onlay bone graft substitute.
AB  - The disadvantages of autogenous bone grafts has prompted a search for a
      dependable onlay bone graft substitute. A combination of tricalcium phosphate, a
      resorbable ceramic, and osteogenin, an osteoinductive protein, was evaluated as
      an onlay bone graft substitute in a rabbit calvarial model. Twenty-eight
      tricalcium phosphate implants (15 mm diameter x 5 mm; pore size, 100-200 microns)
      were divided into experimental and control groups and placed on the frontal bone
      of 14 adult New Zealand White rabbits. In the experimental animals, 185
      micrograms of osteogenin was added to each implant. In the control animals, the
      implants were placed untreated. Implants were harvested at intervals of 1, 3, and
      6 months, and evaluated using hematoxylin and eosin histology, microradiography,
      and histomorphometric scanning electron microscope backscatter image analysis. At
      1 month there was minimal bone ingrowth and little tricalcium phosphate
      resorption in both the osteogenin-treated and control implants. At 3 months, both
      the osteogenin-treated and control implants showed a modest increase in bone
      ingrowth (8.85 percent versus 5.87 percent) and decrease in tricalcium phosphate
      (32.86 percent versus 37.08 percent). At 6 months, however, the osteogenin
      treated implants showed a statistically significant increase in bone ingrowth
      (22.33 percent versus 6.96 percent; p = 0.000) and decrease in tricalcium
      phosphate (27.25 percent versus 37.80 percent; p = 0.004) compared with the
      control implants. The bone within the control implants was mostly woven at 6
      months, whereas the osteogenin-treated implants contained predominantly mature
      lamellar bone with well-differentiated marrow. All implants maintained their
      original volume at each time interval studied. The tricalcium
      phosphate/osteogenin composite, having the advantage of maintaining its volume
      and being replaced by new bone as the tricalcium phosphate resorbs, may be
      applicable clinically as an onlay bone graft substitute.

PMID- 7638296
TI  - The politicization of the physician.

PMID- 7638297
TI  - Physician workforce definition: who is responsible?

PMID- 7638298
TI  - Ear reconstruction with chondrocutaneous postauricular island flap.
AB  - Skin and cartilage defects from the conchal cavity to the external auditory canal
      were reconstructed with the use of a chondrocutaneous postauricular island flap.
      Although based on the experience of only one case, the authors believe that this
      island flap is extremely useful in the repair of skin and cartilage defects of
      the conchal cavity and the external auditory canal.

PMID- 7638299
TI  - Ogilvie's syndrome as a complication after abdominoplasty: a case report and
      review.

PMID- 7638300
TI  - Postpericardiotomy syndrome: its diagnosis and treatment after muscle flap
      closure of an infected sternal wound.
AB  - After nearly any form of cardiac surgery, an acute febrile illness characterized
      by leukocytosis, pericarditis with pericardial effusion, and pleural effusion may
      occur. In some instances, this postpericardiotomy syndrome may suggest the
      presence of mediastinal infection. Treatment of postpericardiotomy syndrome is
      conservative, and symptoms typically resolve with nonsteroidal antiinflammatory
      medication. We report a case of postpericardiotomy syndrome that mimicked
      recurrent mediastinal infection and developed after muscle flap closure of an
      infected sternal wound. Pericardial, pleural, and periflap fluid accumulated
      postmuscle flap closure and was sterile on culture. A diagnosis of
      postpericardiotomy syndrome was made, and the patient improved while receiving
      oral indomethacin. She has remained free of infection as of the 2-year follow-up.

PMID- 7638301
TI  - Central suspension technique of the midface.
AB  - The central suspension technique is useful in addressing moderate nasolabial
      folds in the lower eyelid. It is limited by the amount of suspension that can be
      obtained on the cheek fat of the midface.

PMID- 7638302
TI  - Reconstruction of below-knee stump using the salvaged foot fillet flap.
AB  - Three cases of below-knee stump reconstruction, using cross-legged, free sole
      flap, free foot filleted flap, and island pedicle sole flap, were reported. The
      variability of the flap size provided satisfactory coverage as needed in all
      cases. The causes of amputation were acute trauma and chronic osteomyelitis. The
      contour of the stump, the sensory recovery, the preserved range of motion of the
      knee joint, and the long-term durability were satisfactory in these patients.
      Some pitfalls of this procedure and criteria for evaluating the distal extremity
      soft tissue with respect to their suitability for use are discussed.

PMID- 7638303
TI  - Alessandro Benedetti, a fifteenth century anatomist and surgeon: his role in the
      history of nasal reconstruction.
AB  - Alessandro Benedetti (about 1445-1525) was Professor of Anatomy and Surgery at
      Padua University. He became famous for the construction of the first anatomical
      theater ever built, where he personally used to carry out dissections. He
      published articles on many subjects, first of all on anatomy. His work Anatomice,
      sive Historia Corporis Humani (Anatomy, or the History of the Human Body), first
      printed in Venice in 1502, was very popular and influential at that time. Of the
      many topics treated in the book, one is of special interest to plastic surgeons,
      i.e., the description of nasal reconstruction by means of a skin flap taken from
      the arm. The procedure is the same as the one the Branca family practiced in
      Sicily in the middle of fifteenth century. It is well known that the Brancas kept
      secret the operation and never published it. Hence, Alessandro Benedetti played
      an important role in the history of plastic surgery because he first reported in
      the Western surgical literature the procedure of nasal repair, later called the
      "Italian" method, almost 100 years before Tagliacozzi's publication in 1597.

PMID- 7638304
TI  - Alopecia: an unfavorable result of using a skin-stretching device.

PMID- 7638305
TI  - The art and science of wound care.

PMID- 7638306
TI  - Endoscopic evaluation of the trigeminal ganglion.

PMID- 7638307
TI  - The use of cold normal saline for vasoconstriction in rhinoplasty.

PMID- 7638308
TI  - The use of cold normal saline for vasoconstriction in rhinoplasty.

PMID- 7638309
TI  - The Massachusetts General Hospital annotated bibliography. For residents training
      in consultation-liaison psychiatry.
AB  - The annotated bibliography for the resident's division of the Avery D. Weisman
      Psychiatry Consultation Service at the Massachusetts General Hospital (MGH)
      equips the residents with a practical knowledge in consultation-liaison (C-L)
      psychiatry for their forays onto the floors of the general hospital. As an
      annotated bibliography, it is not intended to be a comprehensive source for C-L
      training. However, the basic fund of knowledge prepares MGH's psychiatric
      residents in a practical way for the variety of questions posed to the C-L
      service. The authors present this annotated bibliography as a guide for future
      efforts to establish a core content of knowledge for residents training in C-L
      psychiatry.

PMID- 7638310
TI  - Psychosocial assessment of organ transplant candidates. Current status of
      methodological and philosophical issues.
AB  - Psychosocial assessments of candidates for organ transplant surgery are conducted
      to ascertain that potential patients are likely to benefit from the surgery
      through adequate coping, good compliance, and commitment to rehabilitation. Such
      assessments must be based on a realistic analysis of the behavioral demands of
      the transplant patient's role. Reliability of psychosocial assessments has been
      established within some programs, but wide discrepancies in the psychosocial
      criteria that are used exist among transplant centers. Validation studies are
      needed, with particular emphasis on outcomes for the patient and family as a
      whole, that go beyond the question of mere survival.

PMID- 7638311
TI  - Neuropsychiatric consequences of renal failure.
AB  - Renal failure is associated with many subtle, and several distinct, alterations
      in neuropsychiatric function. This review describes the clinical findings, the
      treatments, and the known pathophysiology of the neuropsychiatric effects of
      renal failure.

PMID- 7638312
TI  - Outcomes of cataract surgery in nursing home residents.
AB  - A prospective study of vision-related outcomes of cataract surgery as well as
      cognitive functioning, activities of daily living (ADL) functioning, and
      depressed affect was conducted with 19 nursing home residents scheduled for
      cataract surgery. Also studied were 22 candidates for cataract surgery who
      decided against it. Comparison of both groups at baseline revealed that residents
      who chose cataract surgery were less cognitively and ADL impaired. Analysis after
      cataract surgery showed that visual acuity improved significantly at 4 months and
      was maintained at 1 year after surgery.

PMID- 7638313
TI  - Sleep in Parkinson's disease. The role of depression and anxiety.
AB  - Sleep disorders are frequent and well documented in patients with Parkinson's
      disease (PD). The effect of depression and anxiety on sleep in PD patients has
      not been carefully studied however, despite the fact that both depression and
      anxiety are common in PD and well known to affect sleep in patients without PD.
      In this questionnaire study, sleep, anxiety, and depression were evaluated in 99
      patients with PD and 47 control subjects. PD patients had significantly higher
      scores on a variety of sleep variables as well as on measures of anxiety and
      depression. While anxiety and depression were correlated with some sleep
      measures, neither contributed significantly to overall variance in sleep quality.
      The effect on sleep variables was dominated by on-off symptom phenomena, levodopa
      dose, and age.

PMID- 7638314
TI  - Global assessment of functioning. A modified scale.
AB  - The modified Global Assessment of Functioning (GAF) scale has more detailed
      criteria and a more structured scoring system than the original GAF. The two
      scales were compared for reliability and validity. Raters who had different
      training levels assigned hospital admission and discharge GAF scores from patient
      charts. Intraclass correlation coefficients for admission GAF scores were higher
      for raters who used the modified GAF (0.81), compared with raters who used the
      original GAF (0.62). Validity studies showed a high correlation (0.80) between
      the two sets of scores. The modified GAF also correlated well with Zung
      Depression scores (-0.73). The modified GAF may be particularly useful when
      interrater reliability needs to be maximum and/or when persons with varying
      skills and employment backgrounds--and without much GAF training--must rate
      patients. Because of the increased structure, the modified GAF may also be more
      resistant to rater bias.

PMID- 7638315
TI  - Pain perception and serum beta-endorphin in trauma patients.
AB  - Acute traumatic injury engenders the production of beta-endorphin (BE) and other
      endogenous opioids. Elevated BE concentration putatively correlates with pain
      perception in trauma patients. The authors examined traumatic injury severity,
      pain perception, and BE concentration in patients admitted to an urban trauma
      center. Brief rating instruments for pain and unpleasantness were administered,
      and blood was drawn for BE analysis in 48 trauma admissions and 33 age-, gender-,
      and race-matched control subjects for comparison. The authors found no
      correlation between severity of pain perception and BE, but a significant
      correlation was found between BE and patient body weight (P < 0.05), physician
      pain rating (P < 0.01), and Injury Severity Score (P < 0.001). The results
      suggest that past findings associating trauma pain perception and BE
      concentration are spurious.

PMID- 7638316
TI  - Further evidence for a broader concept of somatization disorder using the somatic
      symptom index.
AB  - Somatization syndromes were defined in a sample of 102 psychosomatic inpatients
      according to the restrictive criteria of DSM-III-R somatization disorder and the
      broader diagnostic concept of the Somatic Symptom Index (SSI). Both groups showed
      a qualitatively similar pattern of psychopathological comorbidity and had
      elevated scores on measures of depression, hypochondriasis, and anxiety. A good
      discrimination between mild and severe forms of somatization was found by using
      the SSI criterion. SSI use accounted for a substantial amount of comorbidity
      variance, with rates of 15%-20% for depression, 16% for hypochondriasis, and 13%
      for anxiety. The results provide further evidence for the validity of the SSI
      concept, which reflects the clinical relevance of somatization in addition to the
      narrow definition of somatization disorder.

PMID- 7638317
TI  - Late-stage neuropsychiatric Lyme borreliosis. Differential diagnosis and
      treatment.

PMID- 7638318
TI  - Continuous droperidol infusion for management of agitated delirium in an
      intensive care unit.

PMID- 7638319
TI  - Countertransference issues in termination of life support in acute quadriplegia.

PMID- 7638320
TI  - Psychiatric manifestations of tuberous sclerosis.

PMID- 7638321
TI  - National Practitioner Data Bank. Just numbers or knowledge?

PMID- 7638322
TI  - Congress should open the National Practitioner Data Bank to all.

PMID- 7638323
TI  - Transparency: a prescription against malpractice.

PMID- 7638324
TI  - Putting the controversy aside, how is the Data Bank doing?

PMID- 7638325
TI  - The National Practitioner Data Bank: the first 4 years.
AB  - The National Practitioner Data Bank became operational September 1, 1990, as a
      flagging system to identify health care practitioners who may have been involved
      in incidents of medical incompetence. Query volumes have grown substantially over
      the Data Bank's first 4 years of operation. The greatest increase has come in the
      number of voluntary queries. By the end of 1994, the Data Bank had processed more
      than 4.5 million requests for information on practitioners, more than 1.5 million
      of which were received in 1994 alone. The proportion of queries for which the
      Data Bank contains information on the practitioner in question has grown as the
      Data Bank has come to contain more reports. During 1994, 7.9 percent of queries
      were matched. The Data Bank contained more than 97,500 reports at the end of
      1994. More than 82 percent of the reports concerned malpractice payments.
      Licensure reports made up the bulk of the rest. Physicians predominate in
      reports, accounting for slightly more than 76 percent of the total. The remainder
      are related to dentists (16 percent) and all other types of practitioners (8
      percent). Since reporting of adverse actions is mandatory only for physicians and
      dentists, the proportion of reports attributable to these types of practitioners
      is higher than it would be if adverse action reporting requirements were uniform
      for all practitioners. State malpractice payment rates and adverse action rates
      vary widely, but a State's rate in any given year is highly correlated with its
      rate in any other year. State malpractice rates are not strongly correlated with
      adverse action rates, neither are the rates for physicians strongly correlated
      with those for dentists. There is a weak tendency for States with smaller
      physician populations to have higher levels of licensure and privileging actions.

PMID- 7638326
TI  - Discordance between LMP-based and clinically estimated gestational age:
      implications for research, programs, and policy.
AB  - This study examines the comparability between the last menstrual period-based and
      clinically estimated gestational age as collected on certificates of live birth.
      It explores whether sociodemographic or delivery characteristics influence their
      agreement and contrasts health status and health care utilization indicators,
      such as preterm, small for gestational age, and adequacy of prenatal care
      percentages, produced by each gestational age measure. The 1989-91 South Carolina
      public use live birth files were used for this analysis. A total of 169,082
      single births to resident mothers were selected for investigation. The clinically
      estimated gestational age distribution exhibited a higher mean and a tendency
      toward even number digit preference. The last menstrual period-based measure
      produced higher preterm and postterm percentages. More than 60 percent of the
      last menstrual period-based preterm births were classified as preterm by the
      clinical estimate. The sensitivity of the clinical estimate was 27 percent for
      postterm births. The overall concordance (the percentage of cases with the same
      value for both measures) was 47 percent, but it varied considerably by
      gestational age. Between 30 and 35 weeks, the clinical estimate exceeded the last
      menstrual period-based value by 2 weeks or more for more than 40 percent of the
      cases. Concordance also varied by race of mother, hospital delivery size,
      trimester prenatal care began, and birth weight. The last menstrual period-based
      and the clinically estimated gestational age distributions exhibited notable
      dissimilarities, produced marked differences in health status indicators, and
      varied in concordance by gestational age and by sociodemographic, prenatal care,
      and hospital characteristics. These systematic differences suggest that a
      transition from the traditionally used last menstrual period-based measure to the
      clinical estimate or a composite measure will not produce uniform results across
      geo-political areas and at-risk groups but will be appreciably influenced by
      population and health care characteristics.

PMID- 7638327
TI  - The cost of a preventable disease: estimated U.S. national medical expenditures
      for congenital syphilis, 1990.
AB  - Reported cases of congenital syphilis have increased rapidly in recent years. The
      purpose of this study was to estimate first-year medical care expenditures among
      1990 incident cases of infants diagnosed with congenital syphilis. The authors
      used a synthetic estimation model to calculate expenditures for congenital
      syphilis as the number of treated cases multiplied by cost per case. The number
      of cases was derived from surveillance data adjusted for underreporting and
      presumptive (false-positive) treatment. Cost per case was based on expected
      hospital and physician charges applied to case treatment protocols appropriate to
      case severity. Base-case estimated first-year medical expenditure for 1990
      treated cases (N = 4,400) in 1990 was +12.5 million. In sensitivity analysis,
      estimates ranged from +6.2 million to +47 million. Substantial reduction in
      congenital syphilis treatment costs could be achieved through targeted public
      health interventions consisting of prenatal maternal screening and contact
      tracing of males testing positive for syphilis. Physicians should be aggressive
      in presumptive treatment of newborns, since this usually prevents future
      disability but represents a small portion of total national expenditure for
      congenital syphilis. More precise data on severe cases resulting in long-term
      disability are needed to make reliable cost estimates.

PMID- 7638329
TI  - Deterring sales and provision of alcohol to minors: a study of enforcement in 295
      counties in four states.
AB  - The authors analyzed patterns of criminal and administrative enforcement of the
      legal minimum age for drinking across 295 counties in four States. Data on all
      arrests and other actions for liquor law violations from 1988 through 1990 were
      collected from the Federal Bureau of Investigation Uniform Crime Reporting
      System, State Uniform Crime Reports, and State Alcohol Beverage Control Agencies.
      Analytic methods used include Spearman rank-order correlation, single-linkage
      cluster analysis, and multiple regression modeling. Results confirmed low rates
      of enforcement of the legal drinking age, particularly for actions against those
      who sell or provide alcohol to underage youth. More than a quarter of all
      counties examined had no Alcoholic Beverage Control Agency actions against
      retailers for sales of alcohol to minors during the three periods studied.
      Analyses indicate that 58 percent of the county-by-county variance in enforcement
      of the youth liquor law can be accounted by eight community characteristics. Rate
      of arrests for general minor crime was strongly related to rate of arrests for
      violations of the youth liquor law, while the number of law enforcement officers
      per population was not related to arrests for underage drinking. Raising the
      legal age for drinking to 21 years had substantial benefits in terms of reduced
      drinking and reduced automobile crashes among youths, despite low level of
      enforcement. Potential benefits of active enforcement of minimum drinking age
      statutes are substantial, particularly if efforts are focused on those who
      provide alcohol to youth.

PMID- 7638328
TI  - Employment-related stress and preterm delivery: a contextual examination.
AB  - Studies of employment-related stress as a risk factor for preterm delivery
      suggest that contextual factors unrelated to occupation, as well as work-related
      characteristics, must be examined in assessing this relationship. In this study,
      the relationship of work and contextual characteristics--assessed at midpregnancy
      and including scores on an occupational fatigue index--to preterm delivery was
      examined among 943 black and 425 white low-income multiparous women who were at
      risk for a poor pregnancy outcome. At 24 to 26 weeks gestational age, a 77-item
      questionnaire was self-administered to obtain detailed information on
      sociodemographic and contextual characteristics, home physical activities, and
      occupational characteristics. Questions in the occupational section of the
      questionnaire included most of those previously used by Mamelle and coworkers in
      1984 and 1987 to construct an occupational fatigue index. The overall preterm
      delivery rate for black women was 14.0 percent and for white women, 9.6 percent.
      No relationships were observed between age, education, or marital status and
      preterm delivery, or between work status, hours per week, transportation, travel
      time, reliability of child care, or home physical activity and preterm delivery
      for either black women or white women. Black (but not white) women who continued
      to work at midpregnancy and who reported being able to take rest breaks when they
      felt tired had a lower preterm delivery rate (10.4 percent versus 21.9 percent; P
      = 0.031) compared with those who could or did not. Generally, scores for
      individual sources and levels of occupational fatigue, as well as total
      occupational fatigue index scores, were unrelated to preterm delivery in this
      relatively homogeneous group of low income high-risk women.

PMID- 7638330
TI  - Law officers' views on enforcement of the minimum drinking age: a four-state
      study.
AB  - Qualitative data on enforcement of the minimum drinking age in the United States
      were obtained through in depth interviews with law enforcement officers in May
      and June 1992. Interviews were conducted with 37 supervisory and line law
      enforcement personnel in 15 city and county law enforcement agencies in four
      States. The selected agencies had varying levels of enforcement as measured by
      arrest rates. Interviews focused on the social and political context of
      enforcement of the drinking age, constraints to enforcement, and officers'
      recommendations for improving enforcement efforts. Officers generally perceive an
      acceptance of youth drinking by many segments of their communities, and they do
      not receive significant encouragement from community members to increase
      enforcement efforts. Political factors are thought to play some role in
      determining enforcement levels, especially in sheriffs' departments. Reported
      constraints on enforcement of the minimum drinking age include resource
      limitations, a number of practical problems, perceptions that punishments are
      inadequate, time and effort required for processing and paperwork, and the low
      status accorded enforcement of the minimum drinking age. Officers report facing a
      number of evidentiary and procedural challenges. Officers suggested a number of
      ways in which enforcement of the minimum drinking age could be improved.

PMID- 7638331
TI  - A community-based approach to preventing alcohol use among adolescents on an
      American Indian reservation.
AB  - This paper examines the effectiveness of a 5-year community-based health
      promotion program to reduce the rate of substance use, particularly alcohol, by
      adolescents on a Plains State American Indian reservation. The program was part
      of the Kaiser Family Foundation Community Health Promotion Grants Program. Since
      a reservation control group was not available, adolescents serving as control
      groups for other Community Health Promotion Grants Program communities, including
      a small sample of rural American Indians, were used as a basis for comparison.
      School-based surveys of 9th and 12th graders were carried out on the reservation
      and in five relevant California control communities--two suburban, three rural-
      in 1988, 1990, and 1992. The results showed that the use of both alcohol and
      marijuana declined substantially among American Indian adolescents living on the
      reservation. Binge drinking (five or more drinks on an occasion) declined from 46
      percent to 30 percent, and marijuana use (in the past month) declined from 46
      percent to 29 percent over the 4-year period. However, there were similar, if
      smaller, declines in alcohol use in the comparison groups. Since there was no
      evidence of a relative increase in exposure to alcohol and drug programs on the
      reservation, the authors are cautious in attributing the significant and
      heartening declines in substance use among adolescents on the reservation to the
      community-based program.

PMID- 7638333
TI  - Correlates of drug abuse among homeless and transient people in the Washington,
      DC, metropolitan area in 1991.
AB  - Sociodemographic correlates of drug use among the general household population
      may have less accuracy and utility for describing risk factors for drug use among
      non household populations like the homeless and transient. This analysis examines
      correlates of past year use of marijuana, cocaine, and needles among homeless and
      transient people in the Washington, DC, metropolitan statistical area (DC MSA)
      and discusses them vis-a-vis traditional indicators of drug use among the general
      household population. Data are from a study conducted in the DC MSA in 1991 that
      used a multistage sampling design and surveyed a random sample of 908 homeless
      and transient people ages 12 years and older. The analysis uses multiple logistic
      regression to assess the independent effect of demographic and other predictors
      on selected drug use measures among this population. Three key socioeconomic
      correlates of drug use among the general household population (educational
      attainment, employment status, and marital status) were nonsignificant predictors
      of drug use among the homeless. However, other factors were significant,
      including past year institutionalization, location within the DC MSA, and stage
      of homelessness. The age group at greatest risk for use of marijuana and cocaine
      in the past year were the homeless ages 26 to 34, but the oldest group (35 years
      and older) had the highest risk of needle use. Although men were more likely to
      have used marijuana and cocaine in the past year, there were no sex differences
      in the use of needles in the past year. Only past year use of cocaine differed
      significantly by race or ethnicity, with a greater likelihood among homeless
      blacks than among homeless whites. Measures of social achievement and
      socioeconomic status related to the prevalence and risks of drug use among the
      general household population have but limited applicability in predicting drug
      use among people who are homeless and transient. Along with other indicators of
      behavioral and health risks,history of institutionalization, urbanization, and
      chronicity of homelessness should be considered to improve the epidemiologic
      assessment of this population.

PMID- 7638332
TI  - Determinants of undernutrition among homeless adults.
AB  - Factors associated with undernutrition were investigated in a broad community
      based sample of 457 homeless adults (344 men and 113 women) who were interviewed
      and examined in a variety of settings during the summer of 1985. Latent variables
      representing drug use, alcohol use, a stereotyped homeless appearance, mental
      illness, poor physical health status, and measured variables of age, sex, income,
      and number of free food sources were used as predictors of undernutrition.
      Undernutrition was indicated with three anthropometric measures (weight, triceps
      skinfold, and upper arm muscle area in the lowest 15th percentile) and one
      observational measure. Thirty-three percent of the sample was undernourished as
      defined by at least one of the anthropometric measures. Undernutrition was
      significantly associated with more drug use, fewer free food sources, less
      income, and male sex. The findings identify persons at risk for undernutrition
      and suggest programs to alleviate their hunger, including increased funding for
      food stamps and other income supports, more free food sources such as shelters
      and souplines, and drug treatment programs.

PMID- 7638334
TI  - 'Dropouts' or 'drop-ins'? Client retention and participation in New Haven's
      needle exchange program.
AB  - Although evidence is accumulating that needle exchange programs can lower the
      risk of parenterally transmitted infections, their effectiveness is compromised
      if they suffer from low client participation. A legal needle exchange in New
      Haven, CT, has been studied since its inception in November 1990, employing a
      tracking system to analyze the characteristics of clients participating during
      the first 20 months of the program. Thirty-four percent of injection drug users
      who enrolled in the program during the study period made only a single visit.
      Younger clients were more likely to be in the single visit group. For clients who
      visited the program more than once, the retention fraction, defined as the ratio
      of total client-specific observed person-days to full enrollment person-days
      during the 20-month study period was 67.7 percent, with a median duration of
      participation of 333 days. Further analysis of the client characteristics, based
      on surveys completed upon enrollment in the program, revealed several predictors
      of continuing participation. Most significant were the observations that (a)
      those injecting for 10 years or longer participated longer than clients who
      injected drugs for less than 10 years and (b) nonwhite injectors participated
      longer than whites. The longest duration of participation (median = 501 days) was
      among nonwhite injectors with 10 years or more of injecting history. There have
      been limited data on client participation in needle exchange programs. This gap
      in information must be overcome to allow thorough evaluations of such programs.

PMID- 7638335
TI  - Support for hospital-based HIV testing and counseling: a national survey of
      hospital marketing executives.
AB  - Today, hospitals are involved extensively in social marketing and promotional
      activities. Recently, investigators from the Centers for Disease Control and
      Prevention (CDC) estimated that routine testing of hospital patients for human
      immunodeficiency virus (HIV) could identify more than 100,000 patients with
      previously unrecognized HIV infections. Several issues are assessed in this
      paper. These include hospital support for voluntary HIV testing and AIDS
      education and the impact that treating AIDS patients has on the hospital's image.
      Also tested is the hypothesis that certain hospitals, such as for-profit
      institutions and those outside the AIDS epicenters, would be less supportive of
      hospital-based AIDS intervention strategies. To assess these issues, a national
      random sample of 193 executives in charge of hospital marketing and public
      relations were surveyed between December 1992 and January 1993. The survey was
      part of an ongoing annual survey of hospitals and included questions about AIDS,
      health education, marketing, patient satisfaction, and hospital planning.
      Altogether, 12.4 percent of executives indicated their hospital had a reputation
      for treating AIDS patients. Among hospitals without an AIDS reputation, 34.1
      percent believed developing one would be harmful to the hospital's image, in
      contrast to none in hospitals that had such a reputation (chi 2 = 11.676, df = 1,
      P = .0006). Although 16.6 percent did not know if large-scale HIV testing should
      be implemented, a near majority (47.7 percent) expressed some support. In
      addition, 15 percent reported that HIV-positive physicians on the hospital's
      medical staff should not be allowed to practice medicine, but 32.1 percent
      indicated that they should. Also, 33.1 percent thought the hospital should be
      more involved in AIDS education. Finally, certain hospital characteristics,such
      as location and for-profit status, were not associated with support for hospital
      based AIDS interventions. Contrary to what was hypothesized,however, hospitals in
      AIDS epicenters were less supportive of the CDC recommendations for some reason
      (X2 = 7.735, df = 1, P = .005).Support for AIDS education and voluntary testing
      is significant among hospital marketing and public relations executives. Over the
      past decade, community marketing and public relations have become an integral
      part of the hospital's business activities.However, financial pressures now are
      forcing hospitals to restrict these efforts. Findings reported in this paper
      suggest that future health care reform may assist public health aims by
      redirecting these endeavors towards the fight against AIDS and other preventable
      diseases, not eliminating them. Additional research is needed to determine why
      executives in AIDS epicenters are less supportive of large-scale hospital HIV
      testing and counseling in comparison with those outside these areas.

PMID- 7638337
TI  - HealthScope: a model for a low cost health education program using commercial
      television.
AB  - HealthScope is a health education based on the Health Belief Model that uses
      television and print materials. It was designed for a number of agendas--(a) a
      desire by health educators to provide health information to a broad audience at a
      reasonable cost (b) a desire by the local medical association to promote its role
      in prevention and primary care, and (c) a desire by commercial television to
      expand its coverage of local health issues in a cost-effective way. In its summer
      series, HealthScope included 10 weekly television programs that focused on
      various aspects of disease prevention and health promotion and answered viewers'
      questions on the air. Each program was followed by a bank of physicians answering
      questions on the telephone for 90 minutes. Corresponding fact sheets were
      distributed through a local pharmacy chain. A "healthy weekend" sweepstakes
      contest also was held. Intermediate outcome measures indicated that HealthScope
      had a broad reach and stimulated viewers to seek additional information about
      health. At the same time, the program generated revenue for the commercial
      television station.

PMID- 7638336
TI  - Determinants of breast cancer screening among inner-city Hispanic women in
      comparison with other inner-city women.
AB  - A telephone survey of a random sample of Rhode Island women ages 40 and older
      residing in minority low-income census tracts--census tracts in the lowest
      quartile of a variety of socioeconomic indicators in which at least 5 percent of
      the population was classified as Hispanic or non-Hispanic black--was conducted in
      1991, focusing on breast cancer screening. Hispanic women were found to have
      about half the breast cancer screening rate (20 percent, according to current
      screening guidelines) of other respondents (37 percent). Determinants of
      screening were explored to suggest reasons for this difference. The Health Belief
      Model was used to identify and compare determinants of breast cancer screening
      (sociodemographics, health care utilization, perceived susceptibility to breast
      cancer, perceived seriousness of breast cancer, cues to screening such as a
      provider's recommendation, and the perceived benefits and costs of screening)
      among Hispanics, non-Hispanic whites, and non-Hispanic blacks. Hispanics were
      younger, less educated, and had lower family incomes than other women residing in
      minority low-income census tracts, were less likely to receive medical care, to
      perceive themselves as susceptible to breast cancer, and to perceive breast
      cancer as curable. Logistic regression analyses revealed the importance of use of
      health care, cues for screening, and perceptions of mammography to explain the
      screening behavior of Hispanics and non-Hispanics alike. Access to medical care
      is a significant problem in the Rhode Island Hispanic community, related to
      recent immigration, undocumented immigration, and low income characteristics of
      its members. Efforts to increase long-term screening for breast cancer in this
      community should focus on access while paying attention to its unique perceptions
      of breast cancer.

PMID- 7638338
TI  - Review and needs assessment of materials designed to prevent tobacco use.
AB  - Over the past 25 years, numerous educational materials and strategies have been
      developed for the prevention and control of tobacco use. However, there has been
      no comprehensive assessment of the available materials designed to educate the
      public to avoid the use of tobacco. A search for materials and a review process
      was conducted in the fall of 1993, and a panel of experts reviewed the materials
      that were collected. In conducting the search, 240 persons and organizations
      associated with tobacco control efforts across the United States were contacted,
      and 207 materials were identified and evaluated. All materials were assessed by
      at least two members of the expert panel. Of the 207 items, 188 were found to be
      acceptable according to standardized review criteria. The authors drew
      conclusions about the current availability of tobacco use prevention materials
      and present recommendations for increasing the availability of materials to
      community-level and other control programs.

PMID- 7638339
TI  - NCHS under full sail on the information highway.

PMID- 7638340
TI  - The first edition of 'The Ship's Medicine Chest' (1881).

PMID- 7638341
TI  - CDC Clearinghouse offers new HIV-AIDS Treatment Information Service.

PMID- 7638342
TI  - [Diagnostic imaging in the traumatized child].
AB  - The value of different radiological procedures in the acute care of injured
      children is described. Newly developed techniques, e.g., digital luminescent
      radiography, are discussed. The indications for modern scanning procedures in
      traumatology and their influence on the examination strategy are shown. The handy
      use of ultrasound in abdominal injuries is essential if a laparotomy is
      necessary. Additionally, CT is useful in equivocal cases. Conversely, angiography
      and MRT are less useful in an emergency situation because of the longer duration
      of these procedures. Special problems of medical-legal reports are demonstrated.
      Injuries in the infant and adolescent skeletal system can result in growth delay.
      In contrast to adults, the growing skeletal system of children has the ability to
      correct deformations in time.

PMID- 7638343
TI  - [Craniocerebral trauma in childhood].
AB  - Depending on the clinical symptomatology, computed tomography (CT) is the
      predominant examination technique. CT reliably shows live-threatening intra- or
      extracerebral hemorrhage. Typical localization and distribution of blood allow
      differentiation between extradural and/or subarachnoidal effusion. Dislocation of
      the midline structures or of cortical relief shows the mass effect of
      intracranial hemorrhage. In many cases localized edema can be identified, but
      because of the normally very narrow cortical sulci in children and younger
      people, the general post-traumatic brain swelling is often diagnosed only
      retrospectively. Magnetic resonance tomography is more sensitive than CT
      concerning subtle changes in the depth of the white matter and should be used for
      follow-up studies as a supplementary examination.

PMID- 7638344
TI  - [Thoracic trauma in childhood. Radiologic findings].
AB  - In childhood blunt trauma to the chest wall is more frequent than penetrating
      injuries. Most of these are the result of traffic accidents. Solitary or serial
      rib fractures are seen more often than fractures of the sternum. Complications of
      thoracic injuries are pulmonary contusion, hemothorax and, less frequently,
      pneumothorax. Pulmonary contusion can result in post-traumatic pneumatocele or
      chronic pulmonary hematoma. Injuries of the heart, the great vessels and
      bronchotracheal rupture, presenting initially with pneumothorax, followed by
      atelectasis, rarely occur. Blunt thoracic trauma is frequently associated with
      further injuries (head and/or blunt abdominal trauma). The prognosis also depends
      on the concurrent injuries. The initial evaluation of an injured child is based
      on the chest X-ray and abdominal ultrasound examination. Additional information
      can be obtained by a CT scan in mediastinal injuries.

PMID- 7638345
TI  - [Blunt abdominal trauma in childhood. Value of conventional radiologic and
      ultrasound diagnosis].
AB  - In blunt abdominal trauma in children, the basic diagnostic work-up should
      include, in addition to history, physical examination, routine laboratory and X
      ray studies, ultrasound and color Doppler ultrasonography. With these methods,
      most lesions can be identified both in the acute phase and in follow-up. They are
      also helpful to decide if surgery is indicated or if conservative management is
      justified. The diagnostic hallmarks of the most common organ lesions are
      summarized. Additional imaging studies, e.g. CT, angiography, or MRI, should be
      reserved for specific questions.

PMID- 7638346
TI  - [Efficiency and efficacy of radiologic diagnosis in skeletal trauma in childhood
      and adolescence].
AB  - In a retrospective analysis, 2,006 X-ray examinations of the skeleton obtained
      after trauma in 1,386 children were examined; 354 fractures were diagnosed. X-ray
      films of the skull were requested in 596 (29.7%); fractures were diagnosed in
      only 13 patients (2.2%). The radiological result changed the medical management
      in none of these cases. On the other hand, X-ray after trauma in the extremities
      is indispensable, except for the knee region. Examinations of the lower arm
      showed a fracture in 54.9%, X-ray of the shoulder 47.7%.

PMID- 7638348
TI  - [A new concept for rational emergency diagnosis of polytrauma patients].
AB  - To optimize the emergency care of patients with multiple injuries, a special
      emergency room with integrated radiological equipment has been developed. It
      consists of a linear array of a computed tomography system, a mobile C-arm with
      an integrated scattered radiation grid for conventional films and a C-arm
      fluorographic system. The intent is to avoid delay caused by transport and
      repositioning of the patient. It enables all necessary diagnostic procedures to
      be performed within a minimal amount of time. If there are no emergency patients,
      the room can be divided by a sliding door and the equipment can be used
      separately.

PMID- 7638347
TI  - [Child abuse. Important findings in diagnostic imaging].
AB  - The radiologist must be familiar with all signs of the battered child syndrome to
      prevent misinterpretation. Important clinical signs are hematoma at different
      ages and in uncommon locations. The principle imaging signs are subdural
      hematoma, brain contusion and multiple skeletal injuries sometimes at different
      ages. The parents or the persons responsible for care often neglect mentioning an
      injury. The principle signs are shown and a diagnostic flow chart is presented.

PMID- 7638349
TI  - [Invasion of the growth plate by bone tumors and osteomyelitis in childhood].
AB  - Crossing of the physis by primarily metaphyseal, localized bone tumors and
      osteomyelitis in childhood was rarely observed. Therefore, the physis in
      childhood is considered to be a barrier against the spread of tumors and
      infection. We report five children, in whom MR imaging demonstrated early
      crossing of the physis and spread of the disease from the metaphysis to the
      epiphysis. Follow-up in three children with osteomyelitis showed that antibiotic
      therapy resulted in almost complete resolution of the changes in the physis,
      epiphysis and metaphysis. These observations challenge the concept of the physis
      as a barrier against the spread of tumors and infection.

PMID- 7638350
TI  - [Aneurysm of a persistent sciatic artery. Case report and review of the
      literature].
AB  - A persistent sciatic artery results from lack of regression of the fetal arterial
      blood supply of the leg and is often combined with an abnormally developed
      superficial femoral artery. A rare case of bilateral persistent sciatic artery
      with unilateral thrombosed aneurysm of the right buttock was found. The right
      sciatic artery was completely developed and terminated in the popliteal artery,
      which showed thromboembolic occlusion. The right superficial femoral artery was
      hypoplastic and showed no connection with the popliteal artery. The left sciatic
      artery was incompletely developed, and the popliteal artery was fed by a normal
      superficial femoral artery. All of the 104 cases published of persistent sciatic
      artery were reviewed according to the degree of development, side localization,
      clinical signs and frequency of aneurysms, as well as the morphology of the
      ipsilateral superficial femoral artery.

PMID- 7638352
TI  - [Pediatric syndrome. Sturge-Weber syndrome or encephalotrigeminal angiomatosis].

PMID- 7638351
TI  - [What is the cause of the pathologic fracture?].

PMID- 7638353
TI  - [Metallic dense shadow in coronal CT of the paranasal sinuses].

PMID- 7638354
TI  - [Further studies on the efficacy of inductive chemotherapy in patients with
      locally advanced stage of mammary cancer].
AB  - In a period from 1.01.1979 to 31.12.1984 in the Oncology Centre, Department in
      Cracow, 202 female patients with locally advanced stage of mammary cancer (T3-4 a
      d, N 2-3) were treated with inductive chemotherapy with following local treatment
      completed with maintenance treatment. The aim of this study is to try to show
      distant results of the treatment based on current experiences and to analyse
      failure reasons. Kaplan-Mayer method was used to estimate probability of 3 and 5
      year lasting surviving.

PMID- 7638355
TI  - [Arterial blood pressure of high school adolescents in Cracow--screening test].
AB  - The study aims at determining the actual standards of arterial blood pressure in
      adolescents (the unimode reading) and initial evaluation of risk of hypertension.
      Survey was carried out on sample of 2214 adolescents aged between 15 and 18, (1st
      and 2nd grade), BP was measured by medical staff (ununiformed) in the school
      medical office, between morning and noon, assuming group V auscultation as the
      measure of diastolic BP. Height, body mass and pulse rate was examined; students
      were asked to answer the questionnaire. Average values of systolic BP of 124.7
      (+/- 14) mm Hg, diastolic BP of 73.1 (+/- 8.7) mm Hg, pulse 79.2 per minute, so
      called double product 9987. Searching for the criterion of hypertension, level of
      95 percentiles amounted to: systolic BP of 148 mm Hg (145 in girls, 152 in boys),
      diastolic BP of 88 mm Hg (equal in both sexes). 162 subjects went beyond the
      level (7.3% of population): systolic BP of 106 (4.8% of students), diastolic BP
      of 81 (3.7%); 25 subjects (1.1%) exceeded both values.

PMID- 7638356
TI  - [Use of mineralogic methods for examination of human tissues. I. Methods of
      mineralogic examination].
AB  - Pathologic mineralization in the human body may produce severe morbidity.
      Application of mineralogic methods of investigation makes possible closer
      cognizance of this process, and facilitates prophylaxis and treatment. The
      principles and employment of following methods are discussed: polarized light
      microscopy, transmission and scanning electron microscopy, infrared spectroscopy,
      X-ray diffraction, atomic absorption spectroscopy, electron microprobe, and
      neutron activation analysis.

PMID- 7638357
TI  - [Use of mineralogic methods for examination of human tissues. II. Mineralization
      of heart structures].
AB  - Using mineralogic methods of investigation there were analyzed 8 mitral and 6
      aortic valves, removed during surgical replacement, and 18 concretions which
      occluded coronary arteries, removed during surgical revascularization procedures.
      In all samples two kinds of mineralization were stated: 1. secret-observed as
      higher than normal content of elements in the tissue, and detected using chemical
      methods only, and 2. apparent-observed as grains and crystals, composed mainly of
      hydrated phosphates and hydroxyapatite, often with deposits of lipids and
      cholesterol.

PMID- 7638358
TI  - [Plasma fibronectin in chronic liver disease--marker of fibrosis?].
AB  - The determination of fibronectin (FN) concentration in plasma has been performed
      in the group of 77 patients (60-with various chronic liver diseases, 6-with AIDS
      IVc, 11-healthy patients). The purpose of this study was: evaluation of the value
      of plasma FN determination in assessment the degree of liver fibrosis and the
      degree of liver damage. The obtained results were compared with routine
      biochemical tests and histopathological picture of liver sections. Among patients
      with liver diseases, we observed that plasma FN concentration was significantly
      lower only in the group with decompensated liver cirrhosis, in relation to
      control group. Non significant lower values of FN was observed in the group of
      patients with chronic hepatitis, as well as non significant higher ones in the
      group with cholestasis and fibrosis. It has been concluded that determination of
      plasma FN concentration has not any importance in evaluation of degree of liver
      fibrosis and its only one from many functional liver tests.

PMID- 7638359
TI  - [Bacterial endocarditis in patients treated with maintenance hemodialysis].
AB  - Bacterial endocarditis (BE) is one of the most severe complications of
      hemodialysis (HD). The aim of the study was to analyse frequency and severity of
      BE in patients treated with HD in our dialysis unit. During the period 1969
      1993276 patients were treated with HD in Gdansk. In 23 cases (9F, 14M) HD
      treatment was complicated with BE. Patients were divided into two groups on basis
      of diagnostic criteria: I-13 patients (5F,8M) with BE diagnosed by means of
      clinical picture and positive blood culture.; II-10 (4F, 10M) with diagnosis
      additionally confirmed by echocardiography. In patients from group I BE was
      observed more often during the first 2 years of HD. In group II during 3-5 years
      of dialysis therapy, gram negative microorganisms were the most frequent
      etiological factors. The mean period of antibiotic therapy was 35 days. In all
      patients from group II changes in the bicuspid valve, in 60% of them additionally
      in aortic valve and in one patient also in the tricuspid valve were observed. In
      five patients changes in the parietal endocardium were also present. Development
      of organic valvular changes was observed in nine patients. Seven of 22 patients
      died during the acute phase of BE and two others from complications connected
      with BE. The longest survival of patients after BE was over 10 years.
      CONCLUSIONS: 1. The threat of BE in patients treated with HD decreased between
      1987 and 1993 in comparison with the initial period of our HD station
      operations.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7638360
TI  - [Diabetic nephropathy--methods of preventing and inhibiting progression].

PMID- 7638361
TI  - [Mucinoses].

PMID- 7638362
TI  - [All-trans-retinoic acid in differentiation therapy of hemo-cytopathic
      proliferative diseases. II. Retinoids in clinical practice].

PMID- 7638363
TI  - [Myocardial infarction complicated by shock and pulmonary edema during cesarean
      section].

PMID- 7638364
TI  - The pathophysiological role of mucus production in inflammatory airway diseases.

PMID- 7638365
TI  - Hysteresis of airways and lung parenchyma.

PMID- 7638366
TI  - Fos immunoreactivity assessment on human normal and pathological bronchial
      biopsies.
AB  - The transcription factor Fos is involved in cell proliferation and
      differentiation. Its expression in normal and pathological adult human tissues
      and cells has rarely been studied. We therefore studied bronchial biopsies
      obtained from 14 normal subjects (NS), 18 non-steroid-treated asthmatics, 10
      corticosteroid-treated asthmatics and 10 patients with chronic bronchitis (CB),
      in addition to 34 patients with lung cancer (LC), by immunofluorescence for Fos
      immunoreactivity, using a highly specific polyclonal antibody. Bronchial tissue
      of 0/10 NS, 11/18 non-steroid-treated asthmatics, 1/10 steroid-treated
      asthmatics, 0/10 CB and 1/34 LC expressed Fos. In asthmatic patients, the
      expression was heterogeneous, localized to epithelial cells and correlated with
      the epithelium shedding (tau = 0.45, P = 0.0001). Corticosteroid-treated patients
      rarely expressed Fos, suggesting a role for this proto-oncogene in asthmatic
      bronchial inflammation. Fos was rarely expressed in the normal and pathological
      (CB, LC) proliferative compartment of the human bronchi, suggesting its low role
      in cell proliferation of the large airways.

PMID- 7638368
TI  - Geographical and social class effects on asthma mortality in England and Wales.
AB  - To determine whether asthma mortality is influenced by geographical or social
      factors, a retrospective analysis of deaths from asthma in England and Wales
      between 1979-1987 was performed. Death rates in the 15 Regional Health Authority
      areas of England and Wales were stratified by sex, age group (0-4, 5-34, 35-64,
      and > 64 years), and occupational social class. Detailed analysis was restricted
      to subjects aged 5-64 years because adequate social class data was only available
      over this age range. Death rates were higher in manual occupational groups
      (social class IIIb-V) than in non-manual occupations (social class I-IIIa), but
      on further analysis this effect was confined to males aged 35-64 years. In
      younger subjects (5-34 years), mortality was higher in the south of the country,
      and this difference was significant in males (P < 0.05). In older subjects (35-64
      years), mortality in both sexes was significantly higher in the north of the
      country. This study demonstrates that mortality is not evenly distributed between
      social classes or regions of the country.

PMID- 7638367
TI  - Snoring in twins.
AB  - Snoring is a prerequisite for obstructive sleep apnoea (OSA) and is known to run
      in families. Recent studies have provided sufficient evidence for a familial
      predisposition to OSA. In our study, 492 monozygotic and 284 dizygotic twins were
      contacted by telephone and asked to attend an interview which included questions
      of life habits, medical history, sleep habits and disorders, with particular
      emphasis on snoring. Our study showed that the probandwise concordance rate for
      habitual snoring was higher in monozygotic twins than in dizygotic ones, but the
      difference was not significant. The comparison of concordant pairs for habitual
      snoring vs. concordant pairs for non-snoring confirmed that habitual snoring is
      significantly associated with older age, male gender, higher body mass index
      (BMI), smoking and respiratory diseases. The multivariate analysis in the
      discordant groups confirmed that BMI is more strongly associated to habitual
      snoring in dizygotic twins than in the monozygotic ones. Our logistic analysis
      showed that other variables, such as smoking and respiratory diseases, are
      associated with habitual snoring in dizygotic pairs, but not in monozygotic ones.
      These findings suggest a genetic predisposition to habitual snoring.

PMID- 7638369
TI  - Measures of systemic activity of inhaled glucocorticosteroids in children: a
      comparison of urine cortisol excretion and knemometry.

PMID- 7638370
TI  - Bronchial responsiveness to histamine and methacholine measured with forced
      expirations and with the forced oscillation technique.
AB  - The objective of this study was to compare bronchial challenge tests with two
      substances [histamine (H) and methacholine (M)] and two methods of measuring the
      effect parameter FEV1 and pulmonary impedance [with the forced oscillation
      technique (FOT)] in order to determine which test is the shortest, and gives the
      least (drug) load to the patient. Furthermore, it was considered whether the
      result of one type of challenge test could be transferred to the result of
      another type of test. It was hypothesized that, since the FOT technique requires
      no forced manoeuvres of the subjects and therefore does not affect the airway
      patency, there must be differences in the provocation concentrations for reaching
      the conventional thresholds of 20% decrease in FEV1 (PC20 FEV1) and 40% increase
      in airway resistance measured at 8 Hz oscillation frequency (PC40 Rrs8). It was
      further hypothesized that the interindividual correlations between thresholds for
      both drugs will be low, because both drugs set off different mechanisms for
      bronchoconstriction. Bronchial challenge tests were performed in 23 stable
      asthmatics (15 males and 8 females; mean +/- SD age 30.3 +/- 11.6 years). Their
      mean control FEV1 was 85.2 +/- 12.6% predicted. For both drugs, PC40 Rrs8 was
      three-fold lower than PC20 FEV1. The within-drug correlation between log PC20
      FEV1 (H,M) and log PC40 Rrs8 (H,M) was quite good [r(H) = 0.73, r(M) = 0.68]. The
      between-drug correlation of log PC20 FEV1 (H) and log PC20 FEV1 (M) was equally
      good. However, the 'between-drug' correlation of log PC40 Rrs8 (H) and log PC40
      Rrs8 (M) was low (r = 0.36).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7638371
TI  - Salmeterol and formoterol in partially reversible severe chronic obstructive
      pulmonary disease: a dose-response study.
AB  - When testing the response to beta 2-agonist drugs in severe chronic obstructive
      pulmonary disease (COPD), a dose-response assessment should be undertaken. This
      study compares the time course of inhaled salmeterol (25, 50 and 75 micrograms)
      and formoterol (12, 24 and 36 micrograms) at different doses in a group of 12
      patients with partially reversible, but severe COPD (FEV1 of 12-32% of predicted
      values after beta 2-agonist drugs had been withheld for 24 h). All doses of
      salmeterol and formoterol induced a significant (P < 0.01) spirometric
      improvement over the 12-h monitoring period, when compared to the spirometric
      improvement after placebo, but while formoterol induced a dose-dependent increase
      of the FVC, FEV1 and FEF50, this was not the case for salmeterol. In fact, 75
      micrograms salmeterol did not produce a further improvement of these parameters.
      Mean peak bronchodilation, expressed as the increase in FEV1 over baseline
      values, occurred 2 h after inhalation of the three doses of salmeterol, and 1 h
      after inhalation of the three doses of formoterol. A comparison of 50 micrograms
      salmeterol with 12 micrograms or 24 micrograms formoterol (clinically recommended
      doses), showed that improvement of FEV1 after salmeterol was statistically (P <
      0.05) higher than that after the two doses of formoterol, although the mean peak
      bronchodilations were similar. This was because salmeterol has a longer duration
      of action than formoterol. These data demonstrate that salmeterol is equally
      effective as, but longer-acting than, formoterol at clinically recommended doses
      in patients suffering from COPD, with severe airway obstruction.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7638372
TI  - Comparison of fluticasone propionate and sodium cromoglycate for the treatment of
      childhood asthma (an open parallel group study).
AB  - Inhaled corticosteroids are highly effective in the treatment of asthma at all
      ages and their use in younger children is increasing. As concerns exist about the
      long-term systemic side-effects of high dose inhaled corticosteroids, current
      guidelines continue to recommend sodium cromoglycate (SCG) as first line regular
      medication for children with frequent symptoms. Few published studies have
      compared the safety and efficacy of inhaled corticosteroids with SCG in children.
      This study compares SCG with the new inhaled corticosteroid, fluticasone
      propionate (FP), which has theoretical advantages over other currently available
      corticosteroids due to its negligible oral bioavailability. This was a
      randomized, open, multi-centre, parallel group comparison of 50 micrograms FP
      twice daily and 20 mg SCG four times daily over 8 weeks, preceded by a 2-week
      baseline period. Sixty-two general practices and two hospital centres enrolled
      225 asthmatic children aged 4-12 years (110 received FP; 115 received SCG).
      Outcome measures improved in both groups, with a significant difference in favour
      of FP for the key variables of mean morning and evening % predicted PEFR and % of
      symptom-free days and nights. No significant difference was observed for FEV1, or
      relief medication use. Two children taking FP and 10 children taking SCG withdrew
      because of adverse events. This study showed that low dose FP was effective and
      superior to SCG in young children with mild-moderate asthma. Safety studies of
      longer duration are needed before changing the current recommendations for
      inhaled corticosteroid therapy.

PMID- 7638373
TI  - Death in notified cases of tuberculosis in Edinburgh: 1983-1992.
AB  - Between 1983-1992, 730 cases of tuberculosis were notified in the Edinburgh area
      (population 6 x 10(5)). A review of available records identified 79 deaths (10.9%
      of all notifications). Thirty-seven patients (5.1%) died in the year following
      notification, 14 of these (five females, nine males; median age 71 years) due to
      tuberculosis. Five of these 14 deaths occurred within 7 days of starting
      chemotherapy and three deaths were due to miliary disease. Of 41 deaths (58%)
      before notification, 29 (19 females, 10 males; median age 77 years) were due to
      tuberculosis (autopsy rate 27/29) and 13 of these 29 deaths, all autopsied, were
      due to cryptic miliary disease. These findings reinforce continuing concerns
      about failure to diagnose tuberculosis, particularly cryptic miliary disease, in
      life.

PMID- 7638374
TI  - Evolution of pulmonary HIV-1 infection in a patient with Pneumocystis carinii
      pneumonia.

PMID- 7638375
TI  - Spontaneous closure of a large emphysematous bulla.

PMID- 7638377
TI  - Pneumomediastinum: an unusual presentation of a carcinoma of the carina.

PMID- 7638376
TI  - Bilateral spontaneous pneumothorax as the presenting feature in
      lymphangioleiomyomatosis.

PMID- 7638378
TI  - Platypnoea-orthodeoxia in cryptogenic fibrosing alveolitis.

PMID- 7638379
TI  - The theoretic blood pH evolution secondary to rise of alveolar tension of carbon
      dioxide during apnoea in anaesthetized humans.

PMID- 7638380
TI  - Air filtration units.

PMID- 7638381
TI  - Carbon dioxide laser bronchoscopy.

PMID- 7638382
TI  - Smoking should be banned on health premises in the U.K.

PMID- 7638383
TI  - Superior vena cava obstruction in a patient with cystic fibrosis and a long-term
      indwelling catheter.

PMID- 7638384
TI  - [Results of the surgical repair of the rotator cuff. Radio-clinical correlation].
AB  - INTRODUCTION: This study was undertaken to evaluate the functional results of
      rotator cuff tear repair. MATERIAL AND METHODS: This retrospective study
      concerned 108 shoulders operated with a minimal follow up of 1 year (mean 5.5
      years). The average age of this masculine population was 55 years. The rotator
      cuff tear involved: 39 times the supra-spinatus, 59 times the supra-spinatus and
      infra-spinatus, 6 times the supra and infra-spinatus and the teres minor, 4 times
      the supra-spinatus and superior part of the sub-scapularis. All these patients
      were reviewed using the Constant's score. The functional results were compared
      with an ultrasonographic study and a radiographic protocol including 5 views.
      Muscle strength was measured objectively with the aid of an isokinetics testing
      (Cybex II). RESULTS: The results were satisfactory concerning pain (67 per cent
      did not suffer anymore) daily activity (78 per cent experienced a slight
      disability) and mobility (92 per cent of the patients had an anteflexion > 120
      degrees and 82 per cent an external rotation > 40 degrees). Concerning strength,
      the results were variable and related to the posterior extension of the tear.
      Most of the patients complained of weakness (mean objective deficit of strength =
      25 per cent), specially a disability during repetitive over head activities. The
      radiographic protocol analysed the humeral head position (16 per cent of
      spontaneous acromio-humeral interval narrowing on the standard X Ray and 43 per
      cent of dynamic narrowing on Leclercq view). The spontaneous narrowing was
      correlated with a severe omarthrosis and a re-rupture of the rotator cuff. All
      these re-ruptures involved an infraspinatus lesion. Dynamic narrowing, with an
      acromial interval < 7 mm, were seen in 71 per cent of the patients with posterior
      extension of the rotator cuff tear explaining the poor final result; the
      ultrasonographic assessment found a thinning (75 per cent of patient) and a
      heterogeneity in the infraspinatus even after repair. We found 14 re-ruptures and
      6 ultrasonographic disorganised structures. DISCUSSION: A well preserved external
      rotation and a centred head gave good result because they were associated with
      the integrity of the infra-spinatus, essential to the muscular balance of the
      rotator cuff and necessary for the dynamic and static centering of the humeral
      head. In 71 per cent of the cases, the suture of the posterior cuff tear did not
      allow a good dynamic position of the humeral head. A spontaneous narrowing
      (static view) of the acromio-humeral interval was in relation with a re-rupture
      which evolved to omarthrosis. A dynamic narrowing with a Leclercq radiograph was
      associated with a functional deficit after rotator cuff repair. CONCLUSION:
      Humeral head stabilisation, supplied by posterior muscles of the rotator cuff, is
      essential in prevention of omarthrosis and in recovery of good strength. In
      several specific cases, we think that the transfer of an external rotator muscle,
      with a good humeral head stabilization action, may restore strength.

PMID- 7638386
TI  - [Simultaneous lesions of the rotator cuff and the brachial plexus].
AB  - INTRODUCTION: A simultaneous lesion of the rotator cuff can be associated with a
      lesion of the brachial plexus and should be considered when treating the lesion
      of the brachial plexus. The author assesses the value of isolated rotator cuff
      repair. MATERIAL AND METHODS: 22 patients presented a rotator cuff tear
      associated with axillary nerve palsy. All of these lesions were traumatic in
      origin and in 20 cases were secondary to anterior shoulder dislocation. The
      clinical presentation was that of a "floating shoulder" with a reduction of the
      scapulo-humeral angle when attempting to elevate the arm. This differed from a
      pseudo-paralytic shoulder due to massive rotator cuff tear in which the scapulo
      humeral angle remains open and from isolated paralysis of the deltoid in which
      active elevation of the arm is possible due to the intact rotator cuff. All of
      the patients had surgical repair of the rotator tear without any procedures on
      the deltoid. The delay from accident to surgery was on the average 65 days
      (range: 7 days to 9.5 months). 22 cases were followed for an average of 25 months
      (range: 12 to 45 months). RESULTS: 20 of the 22 cases recovered an active
      elevation of the arm of 120 degrees despite persistent deltoid paralysis in four
      cases. DISCUSSION: Our results show that the rotator cuff, especially the
      supraspinatus constitutes the main "motor" for shoulder elevation.

PMID- 7638385
TI  - [Isolated lesions of the subscapularis muscle. Apropos of 21 cases].
AB  - PURPOSE OF THE STUDY: The goal of this retrospective study is to describe the
      different anatomic lesions of the subscapularis and to precise the diagnostic
      value of the clinical and imaging tests. MATERIAL: Twenty-one cases of isolated
      tear of the subscapularis were operated on between 1989 and 1992. Affecting both
      sex, this lesion happens in younger patients than the rotator cuff tear
      concerning supra or infra-spinatus. The onset was most often traumatic but not
      specific. Four patients had no traumatic history. RESULTS: In 16 cases, the
      complaint was an unspecific chronic painful shoulder. The Jobe test was positive
      in 12 cases. The lift-off test was positive in 9 cases. Arthrography showed
      extravasation of dye into the subacromial bursa in 11 cases. Subscapularis lesion
      was suspected with the presence of dye spot on the lesser tuberosity on the A.P.
      view in external rotation (18 cases). Arthro-CT-scan was diagnostic in 12 cases,
      revealing dye spot touching the lesser tuberosity. At surgery, 3 types of lesions
      were found: complete ruptures or ruptures concerning the superior two-thirds of
      the tendon and letting intact the inferior muscular third (15 cases): partial
      superior lesions (5 cases) and a muscular tear of the inferior two-thirds. The
      long head of the biceps was dislocated in 5 cases, subluxated in 5 cases,
      ruptured in 3 cases and normal in 8 cases. DISCUSSION: The mechanisms of these
      lesions are probably different. The most common mechanism is traumatic but 4
      patients had no traumatic injury. Degenerative changes of the tendon or
      subcoracoid impingement are also evocated. Arthrography permits a good screening
      but arthro-CT-scan is the most accurate to detect the lesion. Presence of dye
      touching the lesser tuberosity is a specific sign of the subscapularis lesion.

PMID- 7638387
TI  - [Ischio-vertebral dysplasia (a dangerous syndrome for the spinal cord)].
AB  - PURPOSE OF STUDY: A previously unreported condition is defined, diagnostic
      features identified, and clinical course and treatment modalities presented.
      MATERIAL AND METHODS: This is a retrospective study of 11 patients with ischio
      vertebral dysplasia (IVD), accomplished by record and radiographic review.
      RESULTS: 11 patients were included in the study group, age at presentation from 1
      day to 33 yrs. Follow-up ranged from 5-30 yrs. Involvement of 3 successive
      generations (grandmother, mother and daughter) with similar findings was present
      in 1 family. Common features of IVD include: peculiar facies incomplete
      ossification of the ischial ramus, and a dysplasic scoliosis with a significant
      kyphotic element, constituting a rotatory dislocation. 2 patients followed from
      birth demonstrated the natural history of the condition, beginning without spinal
      deformity, and progressing to significant deformity. The spinal deformity was
      manageable surgically. The scoliosis ranged from 10 degrees to 235 degrees, and
      the kyphosis from 0 degrees to 200 degrees (the 10 and 0 being at day 1 of age).
      6 patients incurred neurological sequelae, either spontaneously or associated
      with surgical treatment. 2 patients died, 1 due to cardiopulmonary failure at age
      33; the 2nd was an infant with severe neurologic and cardiopulmonary
      complications due to the spinal deformity. Multiple surgical approaches to the
      problems were employed. Analysis of results permitted formulation of a logical
      and successful approach to the problem. Pre-op mean kyphosis = 112 degrees, post
      op at maximum follow-up = 67 degrees. Deformity stabilization and neurologic
      normalcy was produced in every patient operated but 1. DISCUSSION: The
      characteristics of the syndrome are clear, as is the progressive nature of the
      deformity. The very high risk of neurologic involvement is emphasized. Before age
      10, circumferencial fusion prevents progression and neurologic deterioration.
      Older patients require gradual correction by skeletal traction, followed by
      anterior concave strut stabilization and posterior fusion (with or without
      instrumentation). Extreme care is necessary for protection of the particularly
      vulnerable neurologic structures. Early stabilization and correction is
      recommended for prevention of the deterioration of cardiopulmonary function.

PMID- 7638388
TI  - [Results of total knee prostheses with or without preservation of the posterior
      cruciate ligament].
AB  - PURPOSE OF THE STUDY: This study was undertaken to assess the functional
      repercussion of retention or sacrifice of the posterior cruciate ligament in
      total knee replacement. MATERIAL: Two homogeneous randomised series of 24 cases
      were matched. They concerned primary total knee arthroplasty for osteoarthritis
      using the same prosthetic design. In case of sacrifice of the posterior cruciate
      ligament, the prosthesis included a substitution system constituting the only
      difference between the two types of implants (the design of trochlea, femoral
      condyle and tibial plateau were identical). METHODS: Functional assessment was
      performed according to the Hospital for Special Surgery score, at a minimal
      follow up of 12 months. The Student "t" Test was used for statistical analysis.
      RESULTS: In cases with posterior cruciate retention, the mean HSS score was 86.6.
      In postero-stabilised cases. this score was 87.7: a non significant difference.
      The mean range of flexion was 108 degrees for the retaining cases versus 113
      degrees for the postero-stabilised ones: a non significant difference.
      DISCUSSION: The functional outcome seems to be the same whether a postero
      stabilised or a posterior cruciate retaining total knee prosthesis was used. The
      latter technique requires more care for ligament balancing, tibial cuts and
      exposure. CONCLUSION: The authors believe that there is no benefit to expect at
      mid-term follow up from retaining the posterior cruciate ligament in total knee
      replacement.

PMID- 7638389
TI  - [Infected total knee prosthesis. Guidance for therapeutic choice].
AB  - PURPOSE OF THE STUDY: The aim of the study is to assess the functional results
      and septic evolution in the treatment of infected total knee arthroplasties.
      MATERIAL AND METHODS: 22 patients were reviewed; 8 were initially treated in our
      institution and 14 transferred from other hospitals. Articular debridement alone
      leaving the prosthesis in situ was initiated in 3 of our 8 patients as well as in
      6 of the transferred cases. In both groups, this procedure appeared to be a
      failure. Prosthetic-reimplantation procedure was elected in 10 patients either as
      a one-stage (5 cases) or a two-stage surgery (5 cases). This has been
      successfully rated in 7 cases. Femoro-tibial arthrodesis was performed in 15
      patients, three of them being a failure of the prosthetic reimplantation. Follow
      up ranges from 16 months to 9 years with well documented records. RESULTS: As
      stated earlier, articular debridement alone has not proven to be a helpful
      procedure since it did not eradicate the septic complication in any case.
      Prosthetic reimplantation has been a successful treatment in 7 of the 10
      attempted cases. The one-stage procedure is providing the best functional result.
      Recurrent infection occurred in 3 cases: there were patients with poor host
      defense (diabetes, arteritis, old age, ...) with resistant bacteria complicating
      a hinge-knee prosthesis. Femoro-tibial arthrodesis was achieved in 10 of the 15
      patients and necessitated all together 23 surgical operations. The highest union
      rate was observed in cases where sterile conditions were achieved, fixation being
      performed with an intramedullary nail. Failure of arthrodesis confines the
      patients in such an uncomfortable situation that 2 of them has asked for an
      amputation. DISCUSSION AND CONCLUSION: Early surgical debridement may
      occasionally salve a prosthesis when it is performed shortly after the onset of
      infection, in an unloosened unconstrained prosthesis infected by a low-virulence
      organism. In our study, no patient but one met those criteria. For those cases
      nevertheless, our procedure of choice is now the one-stage reimplantation who
      seems to be more effective for eradicating the infection and gives rise to a
      better clinical result. The two-stage reimplantation is the current procedure for
      handling an infected knee prosthesis. Some patients are still excluded from this
      procedure because of their poor health condition, bone loss, inadequate viability
      of skin and extensor mechanism or an uncontrolled sepsis. For such a case,
      arthrodesis remains the most reliable method of management, especially when it
      can be stabilized with an intramedullary fixation, which implies to perform a two
      stage arthrodesis.

PMID- 7638390
TI  - [Surgical limb lengthening in patients of short stature. Indications,
      complications and results].
AB  - PURPOSE OF THE STUDY: The authors report their experience in limb lengthening in
      55 patients with short stature. MATERIALS AND METHODS: Surgical treatment must
      begin at the age of 13-15 years to obtain better collaboration from the patient
      which is necessary to obtain a good result. The general indication for surgery
      includes short stature between 110 and 150 cm. The major indication is
      disproportionate short stature. The authors have operated on some cases of short
      stature in which there was a disproportion between thighs and legs and other
      short stature without disproportion. In these patients they have tried to obtain
      the greatest lengthening compatible with good appearance. RESULTS: Examining the
      complications, the authors have noted that the rate of bone infections is clearly
      decreased, whereas non union, a frequent complication of the original Wagner
      method, has completely disappeared. The use of a circular device has not caused
      an increase of neurological complications, which on the contrary have diminished.
      DISCUSSION: Surgical lengthening of the lower limbs in disproportionate dwarfism
      can lead to cosmetic, functional and psychological benefits. The treatment is
      long and demanding, for the surgeon and especially for the patient. For this
      reason it is necessary to carefully evaluate the motivations of the patient, who
      must be well aware of the achievable results as well as of the possible
      complications. CONCLUSION: Such a treatment must be undertaken in specialized
      centers, not only owing to surgical difficulties, but especially because it
      requires a continuous clinical check and a strong post-operative physiotherapy.

PMID- 7638391
TI  - [Surgical treatment of chronic hematogenous osteomyelitis. A series of 42 cases].
AB  - INTRODUCTION: Chronic hematogenous osteomyelitis (C.H.O.) is still a scourge of
      the non-industrialized countries. The authors operated on 420 cases of C.H.O. in
      Algeria between 1968 and 1987. A computerized analysis of the results of the
      surgical treatment of these 420 cases was made in Brussels, Belgium, by two of
      the authors. The results of this computerized study are exposed. MATERIAL AND
      METHODS: 67.1 per cent of the patients were male and 37.9 female. 68 per cent
      were operated before 16 y. of age. 381 lesions involved tubular bones: femur,
      tibia and humerus were the most frequent locations. Only 4 per cent of the cases
      had never presented a suppuration. Cultures of Staphylococcus were positive in 82
      per cent of the cases. Surgical procedure was classical--bone window opening,
      sequestrectomy and saucerisation--in 359 cases. Operation was limited to soft
      tissues in 22 cases and bone resection was performed in 39 cases. Post-operative
      antibiotherapy was administered for a period of 10 to 60 days according to the
      patients. RESULTS: After the first operation with the classical procedure,
      results were satisfactory in 72 per cent of the cases but "healing" was achieved
      in 95 per cent of the cases after 2, 3, 4 and up to 6 operations. After bone
      resection, the rate of permanent healing was of 100 per cent. Follow-up was of
      more of 1 year (up to 22 y.) in 80 per cent of the cases. DISCUSSION: As far as
      classical procedure is concerned, a computerized analysis made according to 34
      variables, led to the conclusions that the following variables could have a
      positive influence upon the prognosis: surgical team's experience, young age of
      the patient at the time of operation, subacute onset of the disease, location on
      the humerus, diaphysis of long bones, membranous and short bones, small number of
      sinuses, sclero-geodic radiologic appearance of the lesions, thin perifocal
      radiologic condensation, periosteal reaction, post-operative administration of
      two antibiotics. Excellent results of bone resection are pointed out but
      attention is drawn on the dangers of extending the indications for resection to
      the tubular bones. CONCLUSION: The authors conclude that improvement in the
      results of the surgical treatment of C.H.O. may only take place after improvement
      of the quality and duration of chemotherapy: that is confirmed by the results of
      a clinical trial they organized on the role of post-operative administration of
      Amoxicilline + Clavulanic Acid for a period of 60 days after surgery: 44
      patients, 2 lost to follow-up, 4 failures and 38 "healings" (90.5 per cent) at 2
      years and more.

PMID- 7638392
TI  - [Anterior instability of the shoulder associated with fracture of the coracoid
      process. Apropos of 3 cases].
AB  - PURPOSE OF THE STUDY: The aim of this paper is to present an unusual lesion
      associating anterior instability of the shoulder with a fracture of the
      horizontal part of the coracoid process. It emphasizes surgical treatment using
      the Latarjet procedure. MATERIAL AND METHODS: Three cases are presented: One case
      was a recurrent anterior dislocation of the shoulder associated with a fracture
      of the horizontal part of the coracoid process; an other case was a painful
      shoulder associated with pseudarthrosis of the coracoid process and a fracture of
      the anterior and inferior edge of the glenoid. In the last case there was a
      recurrent dislocation of the shoulder associated with a pseudarthrosis of the
      coracoid process detected intra-operatively. All the patients were operated on
      using the Latarjet's procedure using the fractured coracoid process. RESULTS: The
      three cases had a good result. DISCUSSION: The association of an anterior
      dislocation of the shoulder and a fracture of the coracoid process is very
      unusual. It is often unrecognized because of poor knowledge of this lesion or a
      poor quality of the radiograms performed in the emergency room. The most likely
      mechanism is a direct impact of the humeral head against the coracoid process
      during the dislocation. The fracture is located (as in our 3 cases) at the
      horizontal part of the coracoid process near its elbow and they are often
      associated lesions at the anterior and inferior edge of the glenoid. The
      diagnosis requires good quality radiograms and a Garth's view systematically
      performed after reducing the dislocation. When the shoulder is painful or
      unstable, surgical treatment is performed and the Latarjet's procedure takes care
      of the pseudarthrosis and the instability of the shoulder. CONCLUSION: Isolated
      fractures of the coracoid process are probably uncommon. When there is a fracture
      of the horizontal part of the coracoid process anterior instability of the
      shoulder should be suspected. This is the case when the shoulder has never been
      dislocated and when the standard radiograms are "normal" without "crossing
      lesions" at the anterior and inferior edge of the glenoid or at the humeral head
      (Hill-Sach lesion).

PMID- 7638393
TI  - [Acute hematogenous osteomyelitis. Importance of echography].

PMID- 7638394
TI  - [Apropos of the article "Digastric trochanterotomy in reoperations of total hip
      prostheses. Apropos of 53 cases"].

PMID- 7638395
TI  - [Dedifferentiated chondrosarcoma. A study of 13 clinical cases and review of the
      literature].
AB  - PURPOSE OF STUDY: Dedifferentiated chondrosarcoma is a variant of chondrosarcoma
      of bone consisting in a highly anaplasic sarcoma associated with low grade
      chondrosarcoma. The histopathology and the poor prognosis characterize these
      tumors. The clinical, radiographical and histological features are described
      before proposing a therapeutic approach to improve prognosis. MATERIAL AND
      METHODS: Thirteen cases of dedifferentiated chondrosarcoma having the
      histological requirements described by Dahlin and Beabout were identified and
      treated between 1977 and 1992 at the Cochin Hospital. These tumors represented 10
      per cent of all chondrosarcomas registered in the same period. Eleven cases were
      primary and in two cases the dedifferentiated chondrosarcomas were first found in
      recurrent tumors. The average of age was 53 years. This was a retrospective
      study. The clinical reports, radiograms and histological reports were
      reevaluated. In doubtful cases the histological sections were reviewed. RESULTS:
      The clinical features were no different from chondrosarcoma except for the high
      incidence of pathological fractures. The histology was associated in all cases
      with a grade 1 or 2 chondrosarcoma and a grade 3 or 4 anaplasic component. The
      anaplasic components were: 5 osteosarcomas, 5 fibrosarcomas, 2 fibrous
      histiocytomas, 1 rhabdomyosarcoma. All the patients underwent surgical treatment.
      Only one patient was treated by adjuvant chemotherapy. Among the eleven primary
      chondrosarcomas: two disarticulations were performed. En bloc resection was
      performed in nine patients: one wide margin, six marginal and two intralesional.
      The two secondary dedifferentiated chondrosarcomas were treated by
      disarticulation. No local recurrences were observed after disarticulation or wide
      resection. All patients presented pulmonary metastasis leading to death except
      one patient with only three months follow up. The average survival time was nine
      months (1 to 36 months). DISCUSSION: Prognosis is uniformly poor. The five years
      survival rate is 0 per cent in our series and 10.5 per cent in the series
      published by Unni and Frassica. The physiopathologic hypothesis which prevails is
      that the two histologic components originate from two different primitive cell
      clones, one of which differentiates into a low grade chondrosarcoma while the
      others fails to differentiate and remains a high grade sarcoma expressing
      different morphologic features. Treatment was not always adequate, because the
      diagnosis was missed at time of biopsy in five cases. The biopsies showed the two
      histological components in only six cases. All our patients presented pulmonary
      metastasis excepted one patient. This feature was also noted in other series (70
      to 100 per cent). Those metastasis originate from the anaplasic component.
      Chemotherapy has not been well evaluated for these tumors but its effectiveness
      is evident for treatment of osteosarcoma. CONCLUSION: These tumors, which are
      characterized by their histology and their poor prognosis, are frequently
      inadequately treated. It is necessary to improve the prognosis: by performing a
      large biopsy adjusted on the lytic bone. by performing a wide resection or
      amputation. We believe that it is necessary to associate a chemotherapy to
      surgical treatment. We have decided to treat our patients with an osteosarcoma
      protocol.

PMID- 7638396
TI  - [Assessment of the use of the Graf ligamentoplasty in the surgical treatment of
      lumbar spinal stenosis. Apropos of a series of 26 patients].
AB  - PURPOSE OF THE STUDY: The aim was to determine the usefulness of a flexible
      stabilization system associated with neural decompression in the treatment of
      lumbar spinal stenosis. 2 points were especially studied: low back pain at follow
      up and Graf system ability to prevent postoperative instability. PATIENTS AND
      METHODS: 26 patients were screened retrospectively with an average follow up of
      29 months. Clinical results were appreciated on the functional Beaujon's score.
      Preoperatively all of the patients had static and dynamic standard X-rays. The
      evaluation of sagital olisthesis was done by using displacement of the posterior
      border of the vertebral body (Wiltse and Winter method's). On the dynamic X-Rays
      we accepted as criteria of instability an olisthesis of 2 mm or more, an angular
      displacement equal or superior to 14.3 degrees in L2 L3, 15.5 degrees in L3 L4
      and 18 degrees in L4 L5 according to the Dvorak's criteria, or a rotatory
      dislocation. Neurological compression was studied from CT scan and dynamic and
      static myelogram. RESULTS: According to our classification results were excellent
      in 8 cases, good in 6 cases, fair in 9 cases and poor in 3 cases. Generally
      results were good on the neurological symptoms (neurological claudication,
      radiculalgia at rest or at exertion) and fair on the low back pain. Only one half
      of our patients had improvement of back pain and 15 per cent were worsened. A
      postoperative destabilization occurred in 27 per cent of our patients (7 levels,
      7 patients). The dynamic preoperative X-rays of these destabilized levels
      detected always 2 or 3 criteria of instability: hypermobility, olisthesis of 2 mm
      or more on the flexion X-rays or rotatory subluxation. For the remaining cases
      only one criteria of instability was found (hypermobility or olisthesis on
      flexion X-rays). CONCLUSIONS: Concerning the postoperative low back pain using of
      a flexible system associated with a neural decompression did not improve the
      results. Concerning the prevention of postoperative instability the Graf system
      did not avoid the slipping of the most instable levels.

PMID- 7638398
TI  - [Trans-trochanteric rotation osteotomy for femoral head necrosis. Long-term
      results].
AB  - PURPOSE OF THE STUDY: The aim of this study was to appreciate the long term
      result of transtrochanteric rotational osteotomy for femoral head necrosis.
      MATERIAL: Twenty six transtrochanteric rotational osteotomies were performed in
      twenty five patients for femoral head necrosis during a five year period (1983
      1988). METHODS: Thirteen hips were operated on with the original Sugioka's
      technique and thirteen with a slightly modified technique (fixation by nail
      plate) in order to obtain rotational control and to avoid a modification of the
      neck-shaft angle. RESULTS: Short-term (1 to 3 years of follow-up) and long term
      results (5 to 9 years of follow-up) are reported. Two patients were lost to
      follow-up. Twelve hips had been revised by hip replacement with a delay to
      revision between 9 months and 7 years. The twelve other hips were reviewed at a
      mean of seven years and the results were satisfactory in only four hips (17 per
      cent). Fifteen hips showed further collapse. DISCUSSION: Its seems that there is
      further vascular compromise when performing rotational osteotomy. Study of
      various parameters does not allow determining good indications for
      transtrochanteric rotational osteotomy. CONCLUSIONS: Long term result of
      rotational osteotomy are very poor and a total replacement will be necessary in
      almost all cases. We have abandoned this technique.

PMID- 7638397
TI  - [Epidural infiltrations in the treatment of lumbar radiculopathy. Apropos of 200
      cases].
AB  - INTRODUCTION: The authors report a prospective study on the treatment of
      radicular compression using epidural infiltrations. MATERIAL AND METHODS: An open
      study was performed on 200 patients suffering from radicular compression due to
      either herniated lumbar discs (124 cases), lumbar stenosis (32 cases) or
      segmental lumbar stenosis (44 cases) and treated by epidural infiltrations.
      RESULTS: Of the 200 patients studied, 74 per cent did not need subsequent
      surgical treatment. Therapeutic effect was influenced by several parameters:
      etiology of radicular compression: 65 per cent favorable results in herniated
      discs; 69 per cent in lumbar stenosis; and 91 per cent favorable results in
      segmental lumbar stenosis; age of patients: 100 per cent favorable in patients >
      70 years, while only very few favorable results in patients < 20 years of age.
      Chronic or acute radicular pain: among the patients who had herniated discs
      requiring subsequent surgery, 65 per cent presented with acute lesions (pain for
      < 4 months). In patients with lumbar stenosis requiring surgery, 80 per cent had
      acute lesion and in patients with segmental lumbar stenosis, no patients
      complained of acute pain. DISCUSSION: Avoiding surgical treatment is not the only
      parameter which should be studied in evaluating the effectiveness of treatment.
      Lassale's pre and postoperative evaluation with a minimum 1 year follow up showed
      improvement in all non surgical cases. When compared to the literature, this
      study shows favorable long term results.

PMID- 7638399
TI  - [Pathological fractures of the femoral neck in hemodialyzed patients. Apropos of
      26 cases].
AB  - PURPOSE OF THE STUDY: This study is based on a retrospective analysis of 26
      pathological fractures of the femoral neck in 19 chronic haemodialysis patients.
      The purpose of this study is to analyze the epidemiological and etiological
      factors of these fractures in relation to osteo-arthropathy of the dialyzed
      patient, as well as the results of various treatments, both curative and
      preventive. MATERIAL AND METHODS: 26 pathological fractures of the femoral neck
      appeared in 19 chronic haemodialysis patients, 11 men and 8 women, 6 patients
      presented bilateral fractures. The patient's average age at the time of the
      fracture was 61 years (27 to 82). The average duration of dialysis was 11 years
      with a minimum of 2 years and a maximum of 21 years. Hyper parathyroidism was
      found in 14 patients, aluminic intoxication in 6 and amyloidosis at the level of
      the coxo-femoral joint 18 times. Surgical treatment consisted of 6
      osteosynthesis, 2 cephalic arthroplasties, 13 modular arthroplasties and 5 total
      hip arthroplasties. For each case, we studied the presence of necrosis of the
      femoral neck due to aluminic intoxication, osteoporosis due to
      hyperparathyroidism and also the presence of amyloidosis without aluminic
      intoxication. RESULTS: Cortisonic necrosis and porosis was found 4 times out of
      26 cases, hyperparathyroidism once, aluminic osteomalacy 3 times and beta-2
      microglobulin amyloid 18 times. Amyloidosis remains the most frequent etiological
      factor. All patients had been operated for median nerve compression in the carpal
      tunnel, usually 2.5 years before appearance of the pathological fracture. Non
      surgical treatment was used 5 times in undisplaced fractures without any sign of
      amyloidosis and was successful 3 times and unsuccessful twice necessitating a new
      operation by osteosynthesis. Out of 6 osteosynthesis performed for fractures
      either with little or no displacement we observed 4 failures, all of them in the
      cases with intra-osseous amyloidosis. Best results were obtained by
      arthroplasties. Modular arthroplasty has given us 11 long term excellent results
      in 11 of 13 cases. DISCUSSION: The analysis of etiological factors shows two very
      different groups. The first one consisted of 8 fractures without coxofemoral
      amyloidosis. The average duration of dialysis was 5 years, average age, 44 years.
      Etiology was 3 times aluminic osteomalacy, once the only factor found was
      osteoporosis and 4 times necrosis and porosis as a complication, not of
      haemodialysis but of renal transplantation with concomittant corticosteroid
      treatment. The second group consisted of 18 fractures with hip amyloidosis in 14
      patients. The average age was 63.5 years, the dialysis duration was 11.5 years,
      the two extremes 5 and 21 years. Etiology was beta-2-microglobulin amylosis. The
      pathological fracture was due to the presence of voluminous subchondral
      amyloidosis geodes. Amyloidosis always associated with hyperparathyroidism and
      aluminic intoxication in one of 3 cases. Osteosynthesis gave good results only in
      cases presenting no intra-osseous amyloidosis. Modular arthroplasty has allowed
      us to obtain excellent long term functional results with simpler outcome. Total
      arthroplasty should be used only for evident acetabular involvement. CONCLUSION:
      Amyloidosis remains the etiological factor most frequently found in pathological
      fractures of the femoral neck in chronic haemodialysis patients. The study of the
      etiological factors is essential since they will guide us in the choice of the
      mode or treatment. It is totally licit to propose conservative treatment for non
      displaced fractures without osseous amylosis. In all other cases, prosthetic
      replacement is necessary and osteosynthesis contra-indicated. When the acetabulum
      is not altered a modular arthroplasty must be used. We do not recommend
      preventive surgical treatment for patients having a threatening geode of the
      femoral neck as all osteosynthesis realized on amyloidotic bone, even without any
      displacement, resulted

PMID- 7638400
TI  - [Detection of deep vein thrombosis of the limbs by ultrasound in orthopedic and
      traumatologic surgery. Results of 1647 studied patients].
AB  - INTRODUCTION: This study was undertaken to estimate the efficiency of duplex
      ultrasound scanning and its utility to detect deep vein thrombosis in orthopedic
      patients and to describe their features. MATERIAL AND METHODS: A total of 1647 in
      patients, all receiving low-molecular-weight heparin, were investigated from 1989
      to 1993, either for screening because of a high risk of thrombosis (asymptomatic
      group: 930 patients, mean age + SD: 63 + 17 years) or for clinical suspicion of
      deep vein thrombosis (symptomatic group: 717 patients, mean age + SD: 57 + 21
      years). Difference between the two groups mean ages was significant (p < 10(-8)).
      An Hitachi EUB 450 duplex and an Acuson colour duplex 128 XP, with 3.5 MHz and
      7.5 MHz linear probes were used. Veins were tested for compressibility in the
      transverse view from caval site to both ankles. Retrospective analysis of
      patients' database results was done. RESULTS: There was no significant difference
      in deep vein thrombosis rate between screening asymptomatic group (356/930: 38
      per cent) and symptomatic group (2531717: 35 per cent). There was a linear
      relation, in the 2 groups, between age and deep vein thrombosis rate, from 10 per
      cent before twenty to 45 per cent after eighty years old. For a relative risk to
      have thrombosis detected before twenty definite at 1, it was 2.1 for 20-29, 4.9
      for 40-49, 6.2 for 60-69 and 8.6 later than 80 years old. Proximal deep vein
      thrombosis was detected in only 5 per cent (87/1647) of patients. Distal muscular
      soleal veins were the most usual involved sites of thrombosis. Isolated soleal
      thrombosis were detected in 16 per cent (270/1647) of patients. There was no
      significant difference between the deep vein thrombosis rate after total knee or
      hip arthroplasty among selected patients for duplex scanning from 1989, and the
      true prevalence assessed among all the patients who have undergone total hip or
      knee arthroplasty during the last 6 months. DISCUSSION: Pessimistic results
      previously reported for duplex screening among asymptomatic patients are not
      confirmed. Calf vein thrombosis rate assessed with duplex exceeds by 15 to 20 per
      cent the rates assessed by contrast venography, among patients receiving low
      molecular weight heparins. That difference could be attributed to the isolated
      muscular soleal thrombosis usually missed at contrast venography. CONCLUSION:
      Deep vein thrombosis rate among orthopedic surgical patients, is much higher when
      detected with Duplex ultrasound scanning than detected with contrast venography,
      and is related to patient age. Soleal vein thrombosis is the most prevalent.
      Duplex ultrasound scanning is an efficient and useful screening method for deep
      vein thrombosis in orthopedic surgery. Mechanical calf venous pump stimulation in
      association with low molecular weight heparin, has to be evaluated in attempting
      to reduce those muscular soleal veins thrombosis.

PMID- 7638401
TI  - [Blood vessel transfer allowing avoidance of surgical rotation or amputation in
      the management of primary malignant tumors of the knee].
AB  - PURPOSE OF STUDY: The surgical and clinical outcome of a limb-salvaging technique
      for tumors about the knee utilizing autogenous vessel transfer is reported. The
      original indication for these lesions was amputation or Van Nes rotationplasty
      because of vascular encasement by the tumor. MATERIAL: Twelve patients are
      reported: seven females and five males with an average age of 16 years. There
      were nine distal femur and three proximal fibula stage IIB primary malignant
      tumors. METHOD: All patients underwent a local wide resection of the primary
      tumor including the main vessels, followed by local reconstruction of the bone
      and vessels by an ipsilateral vessel transfer. Postoperatively the limbs were
      immobilized in a cast and the patients were treated with intravenous Heparin,
      followed by a single low dose Heparin injection for three months. RESULTS:
      Immediate postoperative arterial occlusion in one patient was successfully
      treated, but eight weeks later another occlusion occurred and an amputation was
      necessary. In another patient, arterial thrombi necrotized two toes; they were
      subsequently amputated. Other local complications were hematoma (two patients),
      superficial skin necrosis (one patient), and deep infection (one patient). All
      were successfully revised surgically. All resections obtained negative margins,
      and there were no local recurrences or distant metastases. In all twelve patients
      the tumor either encased the artery and vein, or the pseudocapsule of the tumor
      touched the vascular adventitia. DISCUSSION: The results show that by patients in
      whom there is attachment of the tumor with major vessels or in whom the vessels
      are encased by the tumor, wide limb-saving resection can be achieved by en-bloc
      resection of the primary tumor and the vessels. In this respect a contamination
      of the vessels is no longer a contra-indication for a limb-saving procedure.
      CONCLUSION: The described method is safe, has a relatively low complication rate
      comparable with rotationplasties and allows a limb-saving procedure.

PMID- 7638402
TI  - [Subtalar arthrodesis for sequelae of calcaneal fractures. Apropos of 57 cases].
AB  - PURPOSE OF THE STUDY: 57 subtalar arthrodesis for sequelae of calcaneal fractures
      were reviewed with a minimum follow up of 6 years 11 months. MATERIAL AND
      METHODS: Bone resection and interposition of bone grafts, stabilized by screws
      were used in 36 cases. Iliac crest grafts were used in 20 cases, cryopreserved
      grafts 15 times and local graft taken on the anterior tibial epiphysis once. No
      surgery was performed on the mid foot. RESULTS: Results were evaluated using the
      grading system described by Mestdagh with 33 good global results, 18 fair results
      and 6 poor results for a total of only 58 per cent of good global results. Of the
      57 cases reviewed, 18 remained painful with a limited range of motion for
      inversion and eversion of the foot. In 18 patients monopodal weight-bearing was
      unstable. Residual oedema persisted in 5 patients. 16 patients continued to limp
      and 3 required the use of a crutch. 7 valgus and 3 varus deviations of the
      hindfoot were noted at follow up with poor tolerance of the varus when compared
      to exaggerated valgus. Podoscopic examination revealed increase anterior pressure
      zones responsible for metatarsalgia which was relieved by corrective shoe inserts
      in 10 patients. Radiographic evidence of fusion could be demonstrated in 55
      cases. There was little or no repercussion on the tibio-talar joint. In the
      Chopart joint we noted 4 cases of osteoarthritis; there were 6 lesions in the
      talo-navicular joint and no repercussion in Lisfranc's joint. 16 complications of
      varying severity were noted with 2 nonunions following use of cryopreserved
      grafts. DISCUSSION: Subtalar arthrodesis for sequelae of traumatic lesion in the
      hindfoot gives good results in 2 cases out of 3. In our series, 26 per cent of
      the patients showed degenerative changes in the mid foot unlike the series
      published by Kempf. As Meary and Mestdagh noted, we found that residual varus or
      valgus deformity > 10 degrees was poorly tolerated as well as modifications > 20
      30 degrees in the vertical ratio between the talus and the calcaneum in the
      horizontal plane. CONCLUSION: Subtalar arthrodesis is a useful technique giving
      good results in 2 out of 3 cases of traumatic sequelae in the hindfoot. Triple
      arthrodesis does not seem indicated when the talus and the calcaneus can be
      realigned before fusion. Talo-navicular arthrodesis, though more easily realized,
      requires blocking a normal joint in order to immobilize a painful joint.

PMID- 7638403
TI  - [Atlanto-axial Pott's disease. Apropos of a case with review of the literature].
AB  - INTRODUCTION: A new case of sub-occipital Potts disease is reported. CASE REPORT:
      A 26 years old female from Senegal was admitted for cervical pain of three months
      duration, neck stiffness and left nasal obstruction with Arnold neuralgia.
      Radiological studies found a C1-C2 rotatory subluxation with an osteolytic
      erosion of the lateral mass of the atlas and destruction of the left atlanto
      axial joint. CT scan and magnetic resonance imaging provided important diagnostic
      clues. Culture of sinus biopsies showed a mycobacterium tuberculosis. Progressive
      reduction of the dislocation and immobilization by minerva jacket for six months
      with prolonged antituberculous chemotherapy provided successful end result.
      DISCUSSION: A review of the literature found 95 cases reported since the
      beginning of this century. The mean age was 20-30 years old. A finding of acid
      resistant bacilli is necessary for diagnosis and requires culture of gastric
      secretion, expectoration, retro pharyngeal mass puncture and other upper
      respiratory tract foci. Radiological signs are discussed. Chemotherapy is the
      mainstay of treatment with immobilization following reduction of the dislocation
      when present. The removal of abscess is discussed as well as bone grafting by an
      anterior or more commonly by posterior approach in case of instability.

PMID- 7638404
TI  - [Surgical correction of osteoarthritic genu varum by the hemicallotasis
      technique].
AB  - PURPOSE OF THE STUDY: The aim of this short study is to highlight the role of the
      hemicallotasis method in correcting genu varum associated with osteoarthritis.
      MATERIAL AND METHOD: 160 cases are described. The first step was to apply a
      Dynamic Axial Fixator (DAF) with a lockable ball joint. A metaphyseal osteotomy
      was performed proximal to the anterior tuberosity of the tibia together with an
      osteotomy of the middle third of the fibula. After an initial 10 to 12 day
      neutralization period, distraction began with gradual axial correction to achieve
      an over correction of 2-3 degrees valgus. This was confirmed by a full limb
      radiograph allowing evaluation of the mechanical axes. The mean duration of
      distraction in this series was 14 days and the fixator was removed on the average
      at 3 months. Partial weight bearing was allowed with crutches on the first
      postoperative day. RESULTS: Preliminary clinical and radiographic review of 58
      patients with an average follow-up of 18 months showed satisfactory results in 80
      per cent of the cases. Clinical evaluation was performed with the standardized
      parameters in use at the Hospital for Special Surgery. Only 2 postoperative
      complications of any importance occurred, requiring early removal of the fixator.
      DISCUSSION: Comparison of the hemicallotasis method with traditional methods
      highlights the quick easy application of the technique with the possibility of
      gradual axial correction and early weight bearing. In addition, the technique
      does not preclude subsequent total knee replacement. CONCLUSION: The authors
      conclude that the method is safe particularly when the indication is well
      determined.

PMID- 7638405
TI  - [Tibiotalar arthrodesis under arthroscopy].
AB  - PURPOSE OF THE STUDY: The authors describe an arthroscopic technique of tibio
      talar arthrodesis. They discuss the advantages, indications and results of this
      technique. MATERIAL: Seven arthroscopic tibio-talar arthrodeses (A.T.T.A.) were
      performed between may 1992 and september 1993 for post traumatic arthritis (five
      following bimalleolar fractures, two following talar fractures). METHOD: Traction
      by means of a transcalcaneus pin was applied to obtain articular distraction.
      Arthroscopic debridement was performed using two standard anterolateral and
      anteromedial portals. The arthrodesis was secured in neutral position by two
      percutaneous tibio talar cannulated cancellous screws. RESULTS: Fusion was
      obtained in all cases over an average period of 12 weeks. No infections or
      cutaneous complications were noted. In one case, however, screw positioning
      caused an injury to a branch of the superficial peroneal nerve. At last follow
      up, according to the Duquennoy grading system, the results were good or very
      good. DISCUSSION: In this study, we noticed a particularly low rate of
      complications, a significantly lesser recovery time and a higher fusion rate
      compared to open ankle arthrodesis techniques. This is probably due to the
      careful handling of the periarticular soft tissues, possible with the
      arthroscopic procedure. The best indication for this procedure seems to be
      "centered" ankle arthritis. However, a significant deviation in one plane, or a
      tibial or talar bone loss needing an autogenous graft is considered to be a
      contra-indication for the procedure. CONCLUSION: A.T.T.A. seems to be a simple
      and reliable technique for centered ankle arthritis.

PMID- 7638406
TI  - [Drug treatment of angina pectoris. Study Group on Angina Pectoris of the
      Ischemic Cardiopathy and Coronary Units Section of the Spanish Society of
      Cardiology].
AB  - Medical treatment in angina pectoris is supported by: 1) slowing in coronary
      artery disease progression; 2) control of the angina episodes and the enhanced of
      the functional status, and, 3) prognosis improvement. The authors describe in
      this review, inside the own experience and the large body of evidence, the
      general measures and pharmacological treatment of both stable and unstable
      angina. There are included some therapeutic options in associated clinical
      conditions.

PMID- 7638407
TI  - [Myocardial revascularization in angina pectoris. Study Group on Angina Pectoris
      of the Ischemic Cardiopathy and Coronary Units Section of the Spanish Society of
      Cardiology].
AB  - Ischemic pain relief and survival are the targets of the revascularization
      treatment in angina pectoris. The authors describe the clinical and anatomic
      indications for revascularization in angina and the reasons for the election
      between surgery and percutaneous transluminal coronary angioplasty.

PMID- 7638408
TI  - [Usefulness of early exercise test after anterior infarction in the diagnosis of
      multivessel disease].
AB  - OBJECTIVE: The aim of the present study was to determine the reliability of early
      exercise test to detect multivessel disease in survivors of an uncomplicated
      first anterior Q-wave myocardial infarction. METHODS: Among 100 consecutive
      patients 64 (aged 55 +/- 10 years) were included in the study. Thirty-four
      patients (53.1%) received thrombolytic therapy and this was considered
      successful, by means of non-invasive criteria, in 24 patients (37.5%). A standard
      symptom-limited exercise test, 11-15 days after myocardial infarction, and
      coronary arteriography, < 72 hours later, were performed in all patients.
      RESULTS: On exercise test 6 (9.3%) patients developed significant ST segment
      depression, 48 (75%) significant ST segment elevation, 5 (7.8%) ST depression in
      inferior leads together with ST elevation in anterior leads and 3 (4.6%) angina.
      Of the 18 patients with multivessel disease 5 (27.8%) developed ST depression, 10
      (55.5%) ST elevation, 1 (5.5%) ST depression in inferior leads together with ST
      elevation in anterior leads and 1 (5.5%) angina. CONCLUSIONS: Our study indicates
      that ST depression in a symptom-limited exercise test performed early after an
      anterior Q-wave acute myocardial infarction is unusual and has low sensitivity
      (27.8%) to detect multivessel disease. ST elevation is the more common finding in
      this test (75%) and has no relation with the severity of CAD.

PMID- 7638409
TI  - [Myocardial contractility and viability. A radionuclide tomography study using
      technetium-99m labeled isonitriles].
AB  - BACKGROUND: There are comparatively few studies evaluating the patterns of
      myocardial viability and its relation with contractility in patients with
      coronary artery disease. The aim of the present study was to quantify the viable
      and nonviable myocardium, using 99m-technetium isonitriles SPET, as related with
      left ventricular regional wall motion abnormalities. METHOD: 61 consecutive
      patients with coronary artery disease were investigated. The severity and
      extension of the defects were evaluated using a qualitative and quantitative
      analysis of the 99mTc-isonitriles SPET and compared with ventricular wall motion
      in contrast ventriculography. An uptake level of 40% of peak uptake or higher was
      considered as indicating viable myocardium. RESULTS: Of the 244 evaluated regions
      (4 per patient), 72 (29%) had normal perfusion, 100 (41%) were ischemic, 25 (10%)
      had a mild irreversible defect and 47 (19%) had a severe irreversible defect.
      Wall motion was normal in 176 regions (72%), 29 (12%) were hypokinetic, and 39
      (16%) were akinetic of dyskinetic. The amount of viable myocardium in akinetic
      and dyskinetic regions (64.8%) was significantly different (p < 0.05) from that
      in hypokinetic (86.1%) and normokinetic (98.8%) regions. Visual assessment of
      uptake underestimated myocardial viability, as quantitative analysis disclosed
      that in 61% of akinetic and dyskinetic regions with severe irreversible defects
      there was more than 50% of viable myocardium. CONCLUSIONS: In 61% of akinetic and
      dyskinetic regions with a severe irreversible defect in perfusion scintigraphy
      positive viability criteria were found. Therefore, visual assessment of the
      myocardial perfusion studies using 99mTc-MIBI SPET underestimates viable
      myocardium. Tomographic studies with quantification of the uptake and defect
      extension are required for a proper evaluation of viable myocardium.

PMID- 7638410
TI  - [Use of transdermal scopolamine in the prevention of neuro-cardiogenic syncope
      induced by the tilt test].
AB  - INTRODUCTION AND OBJECTIVES: The underlying mechanism of syncope induced by head
      up tilt test is still incompletely understood. It has been proposed a sudden
      increase in parasympathetic's activity induced by the excessive activation of the
      cardiac mechanoreceptors. The aim of our study was to evaluate the clinical,
      electrocardiographic and hemodynamic responses to head-up tilt test before and
      after treatment with transdermal Scopolamine (anticholinergic agent). METHODS: We
      studied 17 patients (8 females, 9 males; mean age 43 +/- 19 years) with > or = 2
      syncopal episodes of unknown origin and a positive tilt test (a positive response
      to tilt testing alone or in conjunction with an infusion of isoproterenol was
      defined as the appearance of syncope or presyncope associated to hypotension
      and/or bradycardia). Symptoms developed in 12 patients during the baseline tilt
      (Group I) and in 5 patients after infusion of isoproterenol (Group II). Mean time
      to symptoms was 8.5 +/- 7.9 minutes in group I. All patients were them treated
      with transdermal Scopolamine (1.5 mg/24 hours) and 48 hours later tilt test was
      repeated. RESULTS: In group I, 8 patients (66.6%) became tilt test negative and
      in the remaining 4 patients mean time before the appearance of symptoms was
      increased (8.5 +/- 7.9 vs 16.2 +/- 2.5 minutes; p < 0.05). In group II, 3
      patients (60%) became tilt test negative and in the remaining 2 patients symptoms
      developed after an infusion of higher doses of isoproterenol than in the first
      study. So, with transdermal scopolamine 11 out of 17 patients became tilt test
      negative and time to symptoms was increased in all of the remaining 6 patients.
      CONCLUSIONS: Our study suggest that transdermal scopolamine is an usefull
      treatment in the prevention of neuro-cardiogenic syncope induced by head-up tilt
      test.

PMID- 7638411
TI  - [Mitral insufficiency caused by isolated rupture of the papillary muscle
      secondary to blunt thoracic trauma].
AB  - We report a patient suffering from mitral insufficiency after isolated rupture a
      papillary muscle as a result of a car accident with blunt chest trauma. The
      diagnosis is often difficult due to related multiple lesions which vary the
      clinical picture. Physical exploration, electrocardiogram, enzymatic and nuclear
      scan lack adequate sensitivity and specificity. Echocardiography appears to be
      the most reliable noninvasive diagnostic method now available.

PMID- 7638412
TI  - [Hypertrophic myocardiopathy and ostium primum].
AB  - A 45-year-old male with palpitations and a heart murmur was investigated.
      Echocardiography and haemodynamic study revealed the presence of a ostium primum
      type interatrial communication with left-right shunting and asymmetric
      hypertrophic heart disease. There was no subaortic obstruction, but anterior
      systolic movement of the mitral valve was detected that did not contact with the
      interventricular septum--in part due to the paradoxical motion of the latter. The
      possible benefit of surgery in this infrequent association is discussed, and a
      review is made of the literature.

PMID- 7638413
TI  - [Paroxysmal AV block induced by atrial flutter in acute inferior myocardial
      infarction].
AB  - Conduction disturbances in the acute phase of an inferior myocardial infarction
      are frequent. Paroxysmal AV block and ventricular standstill is, on the other
      hand, an unusual event. We describe a case of paroxysmal AV block precipitated
      by, and dependent on, the presence of atrial flutter. Concealed conduction of
      atrial impulses to the AV node is the likely cause of this form of AV block. The
      transient development, ischaemia related, of a longitudinal and transverse
      dissociation of the AV node, increased the concealed penetration of atrial
      impulses and its effect on subsequent impulse formation, given rise to a form of
      paroxysmal AV block.

PMID- 7638414
TI  - [Aortic prosthetic endocarditis and periprosthetic abscess caused by
      Staphylococcus aureus].
AB  - Prosthetic endocarditis with annular abscess formation is a severe complication
      of cardiac valve replacement fortunately uncommon, though highly lethal.
      Increasing surgical experience and the high mortality with medical management
      have led to a widespread recommendation for early prosthetic replacement. We
      report a case of a 49 year old man with infective endocarditis due to
      Staphylococcus aureus in aortic ascendens prosthetic and aortic valve prosthetic
      complicated with periaortic abscess which was as successful treatment by drain of
      abscess without prosthetic replacement.

PMID- 7638415
TI  - [Adenosine triphosphate in the treatment of supraventricular paroxysmal
      tachycardia: comparison with verapamil].

PMID- 7638416
TI  - [The pros and cons of talc pleurodesis].

PMID- 7638417
TI  - [Is pleural talc therapy dangerous?].

PMID- 7638418
TI  - [Hyperventilation syndrome or syndromes. Between the symptoms and the cortex].

PMID- 7638419
TI  - [Hiccups in adults].
AB  - Hiccoughs are an involuntary spasmodic and coordinated contractions of the
      inspiratory muscles associated with a delayed and sudden closure of the glottis
      which is responsible for the characteristic noise. The pathophysiology of
      hiccoughs have not been elucidated. There have only been a few observations
      describing the sequence of inspiratory muscle activation and these suggest that
      the control of hiccoughs is within the central nervous system. The clinical
      circumstances associated with acute benign hiccoughs are both numerous and
      disparate. In these cases, when they stop spontaneously or as a result of simple
      physical manoeuvres hiccoughs do not require any particular medical attention.
      Chronic hiccoughs, defined as hiccoughs persisting for more than 24 hours or
      recurring as repetitive attacks are a rare phenomenon. The causes cover the whole
      of organic pathology. Systematic protocols of complementary examinations most
      often enable an underlying organic cause to be found. Amongst these, particular
      attention should be paid to oesophageal causes by the reason of their being the
      most frequent. An important place should be reserved for the aetiological
      treatment as is frequently enables a remission of chronic hiccough.

PMID- 7638420
TI  - [Is atopy a risk factor of occupational asthma?].
AB  - General reviews about occupational asthma divide the susceptible allergens
      capable of initiating asthma into two distinct groups: those of high and of low
      molecular weight. Atopy would be a risk factor for developing occupational asthma
      to high molecular weight allergens but not to those of low molecular weight. In
      this work we have examined several studies and have analysed in a critical manner
      the relationship which exists between atopy and occupational asthma. The high
      molecular weight allergens studied were: snow crabs, laboratory animals, flour,
      proteolytic enzymes and psyllium. Those of low molecular weight were: red cedar,
      isocyanates, phthalic anhydride. Amongst allergens of high molecular weight there
      is a undeniable relationship between atopy and sensitisation to the allergen
      incriminated. However, the relation between atopy and asthma is more debatable
      except for baker's asthma. For more allergens of low molecular weight, atopy does
      not seem to favour the appearance of asthma, however, it may play a role in the
      occurrence of asthma to red cedar. The difference between the two groups of
      allergens is not as clear-cut as in the work that has appeared up until now and
      the exclusion of atopics from being hired would appear excessive.

PMID- 7638421
TI  - [Respiratory re-training in asthma. Theoretical basis and results].
AB  - The treatment of asthma is medical. The prescription of respiratory physiotherapy
      should not be routine. It only appears to be indicated in asthmatics with
      continuous dyspnoea or hypersecretion who are unstable, despite medical treatment
      which is both correctly prescribed and properly taken. Bronchial drainage, on
      condition that certain technical precautions are taken, is only useful in asthma
      with hypersecretion. Asthmatic crises are not relieved by physiotherapy. Standard
      respiratory exercises could have a certain value on hyperinflation in the chronic
      asthma of childhood. They are generally without effect on airways resistance or
      expiratory flow. Likewise, there are reflex massages for relaxation, posture, and
      respiratory exercises which are borrowed from yoga. Techniques for correction of
      posture, used preventively, are only of value in chronic asthma of childhood.
      Respiratory muscle training, in spite of a few successes, is not justified on a
      theoretical basis, at least in those subjects who have not been subjected to long
      term steroid therapy. Overall, exercise training is useful from both the
      physiological and the psychological point of view. The anaerobic threshold would
      seem to be the ideal level of intensity for exercise on the basis of 30 minutes,
      three times a week for subjects who are moderately or severely affected. The rest
      on condition of certain precautions, can participate in the sport of their choice
      (or more or less) without any training in the medical milieu beforehand. However,
      in a minority of these patients the physiotherapists, by their individualised
      approach and their techniques, sometimes represent a useful transition towards
      participating in sports. There is no cost benefit study available.

PMID- 7638422
TI  - [The effect of drugs taken by patients with respiratory pathology on the nature
      of sleep and on respiratory characteristics].
AB  - The influence of medications and the usual taken by patients with respiratory
      disease on the characteristics of sleep and nocturnal respiration is complex, due
      to the fact of the inter-dependence which exists between these two physiological
      domains. Numerous medications have been evaluated for the treatment of nocturnal
      respiratory anomalies observed in patients suffering from chronic airflow
      obstruction or from a sleep apnoea or hypopnoea syndrome. For the greater part,
      the efficacy of these drugs remains limited and in the case of nocturnal sleep
      apnoea no pharmacological approach has an efficacy comparable either to
      mechanical or surgical treatments. It is thus important in these patients to
      appreciate the limits of medications prescribed for a specific purpose and the
      deleterious effect which may occur with certain medications employed for a
      symptomatic goal.

PMID- 7638423
TI  - [An experimental model of pleural adenocarcinoma constructed by the implantation
      of intact human neoplastic tissue in the nude mouse. The prognostic value of a
      lesion of the visceral pleura].
AB  - In certain cases pleural adenocarcinoma can behave like a primary tumour of the
      pleura. If the origin of this type of tumour is not clearly established, the
      macroscopic aspect of the pleura explored by thoracoscopy enables a distinction
      to be made between isolated disease of the parietal pleura and mixed disease of
      both the parietal and visceral pleura. The object of this study was to evaluate
      the prognosis of tumour disease of the visceral pleura. Using a murine model (the
      nude mouse) of cancer of both visceral and parietal pleura induced by implanting
      histologically intact human carcinoma, we have compared the symptoms of survival
      of the two groups of mice as well as the local and regional dissemination and
      metastases of the implanted tumour. The growth of the tumour was suspected by the
      appearance of weight loss, signs of respiratory difficulty and/or cachexia.
      Autopsy examination allowed a measure of the size of tumour dissemination. A
      pleural cancer, histologically identical to the initial human tumour with
      invasion of the neighbouring structures as one sees in man, was obtained in all
      the implants. Nevertheless, contralateral mediastinal lymph node metastases were
      only found in mice with implants on the visceral pleura. The median survival was
      27.9 days and 31 days respectively for implanted mice on the visceral pleura and
      on the parietal pleura. Mice with implants on the visceral pleural lost more
      weight than those implanted on the parietal pleura (p < 0.001). The results of
      this study show that the models of parietal pleura and visceral pleura each
      correspond to an early stage disease and to a stage of advanced disease.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7638424
TI  - [Spontaneous pneumothorax. Results of pleural talc therapy using thoracoscopy].
AB  - The aim of this retrospective study is to evaluate the advantage of thoracoscopy
      and the efficacy of talcage in the treatment of spontaneous pneumothorax (SP).
      Two hundred cases have been analyzed with a follow-up of 1 to 8 years after the
      occurrence of the disorder. The ratio man/woman is 4/1. One hundred and forty two
      pneumothorax are considered as being of idiopathic origin and 58 are associated
      to bronchopneumopathy, with a mean age of 33 and 56 years, respectively. The
      percentage of smokers is 69.5% with a mean smoking of 14 packets/years. The
      endoscopic aspect of pleura is either normal (30%) or shows adhesions (23.5%),
      blebs (17%) or bullaes (29.5%). Thoracoscopy allowed talc poudrage in 191
      patients and allowed to indicate the need for surgery in nine patients. The
      immediate success rate of talcage is 93.7%. In the group of immediate failure
      (6.3%), unexpected bullous structures (8/12) are found at tomodensitometry (TDM),
      as well as during surgery. Late recurrence is reported in 2 cases (1%) at 20 and
      25 months. Radiological sequelaes are minimum (9%). Lung function testing in
      patients with idiopathic pneumothorax (n = 64) shows, before talc poudrage, signs
      of pulmonary hyperdistension (total lung capacity (TLC) at 116% of predicted
      values), reflecting the illness pathology, 3 months after talcage a discrete
      restrictive syndrome (TLC 93%) and one year after the partial recovery of the
      lost volume (TLC 105%). Tomodensitometry revealed to be complementary to
      thoracoscopy in secondary SP and very instructive in idiopathic SP after
      immediate failure of talc poudrage.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7638425
TI  - [Differences in efficiency of continuous positive pressure respiration on the
      diurnal somnolence of patients with sleep apnea/hypoapnea syndrome].
AB  - Diurnal hypersomnia was studied in sixteen patients suffering from the sleep
      apnoea/hypopnoea syndrome (SHAS) Group I, and seventeen snorers Group II. The
      groups were studied in their basal state then after 51 +/- 14 days of continuous
      positive pressure (CPP) in Group I with the aid of clinical scores and of
      multiple latency tests of sleeping episodes (TLME). The patients in Group I
      presented with increased and pathological diurnal somnolence (TLME = 3.9 +/- 2.45
      min) associated with disturbances of oxygen saturation during the course of sleep
      (a significant reduction of the mean SaO2) and of the pattern of sleep
      (significant reduction in light slow sleep at the expense of deep slow sleep,
      with a significant increase in the index of brief arousals). We have found a
      positive correlation between the initial TLME and the mean SaO2 during the course
      of sleep (p < 0.05; R = 0.51) without any correlation with other polysomnographic
      parameters. At the time of the final assessment, the improvement in TLME in the
      patients of Group I was significant (p < 0.001). However, in a sub-group of
      patients (BR: n = 7) the TLME were returned to normal using CPP (16.4 +/- 2.21
      min) while those in patients in the second sub-group (MR: n = 9) the TLME
      remained below ten minutes on CPP (6.18 +/- 1.88 min). In the BR subgroup which
      presented with the most elevated mean initial TLME levels the amplitude of the
      rise of TLME between the two groups was significantly larger. No initial
      polysomnographic difference existed between the two sub-groups.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7638426
TI  - [Chronic hyperventilation syndrome. The role of respiratory re-training].
AB  - This study compares three non-pharmacological approaches to the chronic
      hyperventilation syndrome (CHS). Eighteen subjects were evaluated at the start of
      the study then one and 6 months after having received in a random fashion one of
      the following treatments: group I (teaching approach of one hour on the
      respiratory physiology of the CHS and on breathing techniques; n = 5); group II
      (same approach as in group I with breathing retraining of 8 sessions; n = 8);
      group III (same as group II with the addition of a modified Jacobson's
      progressive relaxation; n = 5). Whereas all three groups had a similar
      symptomatic score at the beginning of the study (although subjects of group III
      had in general higher scores and were symptomatic for a longer period), our
      results show that all subjects improved after 4 weeks, those in group II showing
      the greatest improvement (p < 0.05). This confirms the relevance of applied and
      repeated pedagogy in approaching subjects with the CHS.

PMID- 7638427
TI  - [Pulmonary fibroma].
AB  - The authors report the case of a pulmonary fibroma in a 66 year-old smoker.
      Intrapulmonary localization of solitary fibrous tumors is rare; these tumors are
      more frequently described in pleura. Histologically, the presence of spindle
      cells without nuclear atypy on a collagen background must evoke the diagnosis
      made difficult by the unusual localization.

PMID- 7638428
TI  - [Diffuse pulmonary infiltration at the onset of Waldenstrom's disease].
AB  - The case of an 52 years old female presenting dyspnea and pulmonary infiltration
      is reported. A transbronchial biopsy showing a lymphomatous infiltrate with
      immunohistochemistry using anti-IgM antibody on paraffine embedded section helped
      to diagnose. A monoclonal increase in seric immunoglobin M, led to the diagnosis
      of Waldrenstrom's macroglobulinemia. An initial therapeutic response to
      Chlorambucil was obtained. But a quick recurrence was observed, with an increase
      of seric IgG.

PMID- 7638429
TI  - [Multiple bronchial artery aneurysms in a patient with silicosis].
AB  - We report a case of haemoptysis in a long-standing silicotic in whom
      arteriography revealed saccular aneurysms of the bronchial arteries. Embolisation
      was satisfactory in excluding the aneurysms and leading to a favourable outcome.
      The mechanism of the formation of these aneurysms which is extremely rare was
      discussed with reference to the few reports and literature.

PMID- 7638430
TI  - [Allopurinol hypersensitivity. A possible cause of hepatitis and mucocutaneous
      eruptions in a patient undergoing antitubercular treatment].
AB  - The authors describe a case of drug-induced cytolytic hepatitis probably
      secondary to hypersensitivity to allopurinol which was prescribed incorrectly for
      secondary hyperuricaemia during treatment with pyrazinamide. The diagnosis was
      reviewed in view of the late occurrence of hepatitis in relation to the onset of
      the antituberculous treatment, the absence of a viral aetiology and the presence
      of clinical manifestations, biological and histological features which were
      compatible with hypersensitivity to allopurinol. The authors recalled that the
      type of uricaemia induced by pyrazinamide is most often asymptomatic and does not
      require any treatment with uric acid lowering drugs. Cessation of pyrazinamide is
      justified in cases of symptomatic hyperuricaemia but when the indications for
      pyrazinamide are imperative, treatment with an eliminator of uric acid is
      indicated. Allopurinol is contra-indicated in association with pyrazinamide on
      account of its inhibitory reaction to xanthine oxidase. Xanthine oxidase
      decreases the level pyrazinoic acid, a metabolite of pyrazinamide, which is
      responsible for the inhibition of the tubular secretion of uric acid.

PMID- 7638431
TI  - [The use of high resolution x-ray computed tomography in the diagnosis of
      hypersensitivity pneumopathy to gold salts. Apropos of a case].
AB  - A hypersensitivity pneumonia is rare during gold therapy. The underlying
      mechanism is immunological in origin, of Gell and Coombs Type IV. As there are
      numerous possible pulmonary disorders during the course of inflammatory
      rheumatism treated with gold, the early detection is vital, in order to prevent
      progress to fibrosis. In parallel with broncho-alveolar lavage to look for a T8
      lymphocytic alveolitis, which is very suggestive, high resolution computed
      tomography has a place in the early diagnosis, to characterise the lesions, to
      aid in an aetiological diagnosis, and also to assess progress on treatment. The
      authors present a case of pneumonitis induced by gold with visible interstitial
      lesions on computed tomography, accompanied by significant bronchial distortion
      and bronchiectasis suggestive of fixed lesions. These lesions partially regressed
      following steroid therapy; the diagnostic and prognostic role for high resolution
      computer tomography was discussed.

PMID- 7638432
TI  - [The natural history of allergy in infants and asthmatic children].

PMID- 7638433
TI  - [The protected bronchial brushing technic].

PMID- 7638434
TI  - Dose-dependent systemic human immunodeficiency virus infection of SCID-hu mice
      after intraperitoneal virus injection.
AB  - SCID mice were engrafted with human foetal liver, thymus and lung. Human cells
      were subsequently detected among peripheral blood leukocytes for 81% of tested
      animals and in tissue implants for 100% of tested animals. SCID-hu mice received
      intraperitoneal injections of human immunodeficiency virus type 1 (HIV1) at from
      20 up to 20,000 median tissue culture infectious doses (TCID5). HIV1 infection
      was detected by means of cell culture and polymerase chain reaction both in blood
      and implants, up to 58 days after infection. The rate of infection was dependent
      upon the inoculated dose: the frequency of thymus infection ranged from 14% with
      20-500 TCID50 up to 100% with 20,000 TCID50. HIV1 infection was detected less
      frequently in blood leukocytes than in thymus. Thymus virus load ranged from 40
      to 50,000 HIV1 provirus copies per million cells and was not correlated with
      either infectious dose or viraemia. Thymus T-cell depletion was observed mainly
      in the CD1+4+8+ immature thymocyte compartment. The same rate of SCID-hu mouse
      infection was obtained using three different primary HIV1 isolates, suggesting
      that infection was not restricted to a few particular virus strains. The systemic
      infection of SCID-hu mice following intraperitoneal virus injection mimics some
      traits of human HIV infection and provides a promising, novel approach for future
      investigations in this field.

PMID- 7638435
TI  - Purification and characterization of a factor which inhibits retrovirus
      replication.
AB  - Chick embryo cells (CEC) secrete a factor which inhibits HIV1 replication. Non
      productive infection of CEC with vesicular stomatitis virus increases 5-10-fold
      the synthesis of this factor. After purification by FPLC the biological activity
      is associated with a heat-resistant protein of approximately 150 kDa, composed of
      two subunits of 70 and 58 kDa and charged negatively. Monoclonal antibodies
      raised against this protein block the inhibitory activity of the purified protein
      and react with the 150-kDa and 58-kDa proteins in Western blots.

PMID- 7638436
TI  - Replication of human herpesvirus type 6 (strain AJ) in JJHan cells grown in
      protein-free medium.
AB  - The human T-cell line JJHan, commonly used as a substrate for human herpesvirus
      type 6 (HHV-6) replication, was established in a protein-free 1:1 mixture of
      Ham's F12 and Iscove's modified Dulbecco's medium. After 250 passages (4 years)
      in protein-free medium, the cells, designated JJHan-PF, were cocultured with
      JJHan cells chronically infected with strain AJ of HHV-6 conventionally grown in
      serum-supplemented medium. The production of viral antigen was monitored by
      indirect immunofluorescent antibody staining. The infectivity of the virus in
      JJHan-PF cells was similar to that in JJHan cultures as shown by HHV-6 antigen
      detection using a convalescent phase serum. The results show that JJHan-PF cells
      provide a sensitive substrate for HHV-6 replication without the interference of
      serum or other proteins usually added to the culture medium.

PMID- 7638437
TI  - Host-passage-induced phenotypic changes in crimean-congo haemorrhagic fever
      virus.
AB  - Changes in virulence of Crimean-Congo haemorrhagic fever (CCHF) virus toward
      intracerebrally inoculated suckling mice (SM) were studied in relation to
      different host-passage histories. Two CCHF virus strains, one isolated from a
      human and the other from a tick, were passaged through various vertebrate and
      tick hosts and then reisolated and tested for their virulence toward SM. In
      various experiments, SM were inoculated with 12 different viral suspensions, each
      having a specific passage history. Survival curves of SM, which may reflect
      differences in viral strain characters, were established using an actuarial life
      table; differences were evaluated with the log-rank test. Regardless of the
      origin of the strain, CCHF viruses exhibited pathogenicity when passaged among
      SM. However, virulence, as measured by the proportion of deaths in SM, was
      altered following passage through another vertebrate host or tick. The final host
      seems to have a major influence on virulence. Because CCHF virus strains appear
      to vary little in their antigenic characters, it is hypothesized that hosts can
      induce phenotypic changes that modulate viral virulence.

PMID- 7638439
TI  - A simplified method for quantitation of human immunodeficiency virus type 1
      (HIV1) RNA in plasma: clinical correlates.
AB  - Human immunodeficiency virus type 1 (HIV1) RNA was quantitated in the plasma of
      HIV1-seropositive patients using a simplified guanidinium-based extraction
      technique, reverse transcriptase (RT) and the polymerase chain reaction (PCR).
      Plasma samples were obtained from 15 HIV1-seronegative individuals and 38 HIV1
      seropositive patients. Following the extraction of RNA from plasma using
      "RNAzol", HIV1 RNA was reverse-transcribed using random hexamers, amplified by
      PCR and then detected by solution oligonucleotide hybridization. Of the 15 HIV1
      seronegative individuals, 14 were negative for HIV1 RNA by RT-PCR. One high-risk
      patient who was HTLV-I-seropositive but HIV1-seronegative was found to be
      positive for HIV1 RNA by RT-PCR. All 38 HIV1-seropositive patients were positive
      for HIV1 RNA by this technique. The HIV1 RNA levels in plasma varied from 800 to
      500,000 copies/ml. Patients with advanced clinical disease tended to have HIV1
      RNA levels above 25,000 copies/ml. In patients studied serially, an increase in
      plasma HIV1 RNA correlated with a progressive decline in CD4+ T cells and a
      deteriorating clinical course. The simplified quantitative RT-PCR assay for HIV1
      RNA provides a useful tool for the evaluation and management of HIV disease.

PMID- 7638438
TI  - Cerulenin inhibits production of mature virion particles in chick embryo
      fibroblasts infected by influenza A viruses.
AB  - We investigated acylation of haemagglutinin (HA) of type A influenza viruses
      during infection of permissive chick embryo fibroblasts (CEF) treated with
      cerulenin. Fatty acid binding was monitored using a maintenance medium containing
      3H-palmitic acid. Our results suggest that fatty acid acylation of viral
      haemagglutinin may be essential for production of mature viral particles. Indeed,
      palmitoylation was found in infected CEF cells, but was lacking during the
      infectious cycle when cells were treated with a dose of 30 micrograms/ml of
      cerulenin. We discuss the possibility that acylation of virus-induced HA is a
      posttranslational modification regulating correct insertion of virus
      haemagglutinin into the cellular membrane and, as a consequence, controlling the
      maturation of budding influenza virus.

PMID- 7638440
TI  - Advantage of a rapid extraction method of HIV1 DNA suitable for polymerase chain
      reaction.
AB  - We describe a new protocol for extraction of DNA suitable for HIV1 gene
      amplification from clinical samples using "Chelex-100" chelating resin.
      Comparison was made with the classic proteinase K extraction method; 154
      specimens were extracted with both methods and subjected to PCR (polymerase chain
      reaction). The Chelex-100 procedure optimized the yield of DNA recovery and
      minimized contamination due to sample manipulation. It decreased false negative
      results due to PCR inhibitors. A DNA sample suitable for use in PCR was obtained
      in 30 minutes. Chelex-100 treatment is a simple, rapid and low-cost method for
      DNA extraction in clinical laboratories.

PMID- 7638441
TI  - Nucleotide sequences of human T-lymphotropic virus type I (HTLV-I) from a family
      cluster with tropical spastic paraparesis/HTLV-I-associated myelopathy.
AB  - We describe nucleotide sequences of human T-lymphotropic virus type I (HTLV-I)
      proviruses from three symptomatic family members with tropical spastic
      paraparesis/HTLV-I-associated myelopathy (TSP/HAM) from Tumaco, Colombia.
      Polymerase chain reaction was used to clone the U3 region, envelope and tax/rex
      genes of these HTLV-I proviruses from fresh peripheral blood lymphocytes.
      Sequences in U3, env and tax/rex showed 96.9-99.5% conservation when compared
      with sequences from HTLV-I clone ATK, and 96.6-100% when compared with each
      other. The range of sequence divergence within the family was similar to that
      described between unrelated TSP/HAM patients of the same geographical origin.
      Certain mutations were present in all three family members, supporting a
      geographic and/or familial segregation of mutations.

PMID- 7638442
TI  - [Analysis of the location of pain related to sacroiliitis in ankylosing
      spondylitis].
AB  - The characteristics of the pain were investigated in 99 ankylosing spondylitis
      patients (62 men and 37 women) from 17 to 70 years with various developing
      stadies of sacroileitis. The analysis of the sacroileitis pain characteristics
      revealed the dominance of appearing in rest (at night and by day rest) and
      obligatory morning low back stiffness. The intensity of pain was more severe in
      women, more dull, located inguinally, in low abdomen and symphysis. The pain
      propagated on more distant locations (the tight and the leg), shortly or for
      longer period in one and/or both legs. The provocating factors of intensification
      and propagation of the pain were commonly meteorologic factors and rest during
      night and/or day. The evaluation of pain characteristics could be of great
      benefit in diagnostics of the sacroileitis or ankylosing spondilytis which
      usually are not concerned with special significance.

PMID- 7638443
TI  - [Detection of changes in the microvasculature in systemic connective tissue
      diseases--report on methods].
AB  - The aim of the paper is to draw attention to the possibility of an early
      detection of microvascular changes in systemic connective tissue diseases by the
      serial application of capillaroscopy, dermothermometry and digital
      photophlethysmography. A detailed review of diagnostic methods as well as the
      description of own protocol of their application is presented.

PMID- 7638444
TI  - [Comparative study of the effectiveness of lasers and cryotherapy in the
      treatment of painful shoulder syndrome].
AB  - This research tries to determine the difference between two forms of physical
      therapy, as regards their efficiency, in treating the painful shoulder syndrome.
      They are: laser treatment, representing modern technology, and cryotherapy, an
      old and traditional form of treatment. The research comprised 60 patients,
      divided in two groups of 30 patients each. One group was treated by the
      cryotherapy procedures, the other by ten laser treatments, both having in
      addition individual therapeutic exercise for each patient. The difference in
      efficiency regarding both procedures were observed on the basis of objective
      measurable parameters (abduction, anteflexion, retroflexion, external and
      internal rotation, the distance vertebrae prominens and styloid radius) as well
      as in view of anamnestic terms (pain both at rest and in motion) recorded before
      the treatment started and after the application of ten therapeutic procedures.
      The statistic results of data processing showed no significant difference in
      efficiency, regarding the objective parametres, between the two procedures
      treating painful shoulder syndrome. Nevertheless, laser treatment proved more
      efficient in reducing pain. In assessing the efficiency of both treatments there
      is a slight discrepancy as to the outcome between patients and the researcher:
      the patients found the laser treatment more efficient than cryotherapy, while the
      researcher's evaluation was equal both procedures.

PMID- 7638445
TI  - Primary salivary gland-type tumors of the lung.
AB  - Primary pulmonary neoplasms that bear similar histopathologic features to those
      seen in salivary glands are rare. Although their presence has been well
      documented in the literature, it has been primarily in the form of single case
      reports. Consequently, it has been difficult until recently to determine their
      prevalence, clinical behavior, treatment, and spectrum of histopathologic
      features. Moreover, because of the rarity with which these tumors occur, one
      needs to be familiar with their diverse histopathologic features to comfortably
      arrive at the correct diagnosis. Because of their close histological similarities
      to their salivary gland counterparts, careful clinical evaluation is necessary to
      establish the primary nature of these tumors in the lung and to rule out the
      possibility of a metastasis. Another feature that may generate difficulties in
      interpretation is that some of these tumors may share certain histopathologic and
      some immunohistochemical features with each other. This may pose a serious
      problem, particularly when dealing with small biopsy samples. Therefore, the use
      of special studies such as electron microscopy and routine histochemistry may be
      beneficial and must be used in addition to conventional microscopy and
      immunohistochemistry to corroborate the diagnosis. In essence, the diagnosis of
      these tumors requires a combined approach that must include a detailed clinical
      history, a reasonably sized sample for histopathologic evaluation, histochemical
      and immunohistochemical studies, and an ultrastructural examination.

PMID- 7638446
TI  - Malignant mixed epithelial/mesenchymal neoplasms of the lung.
AB  - The existence of biphasic neoplasms occurring primarily in the lung is a well
      known albeit rare event. The spectrum of malignant tumors displaying a mixed
      epithelial/mesenchymal growth pattern is rather narrow when these tumors occur
      primarily in the lung. The two most often encountered neoplasms showing features
      of epithelial and mesenchymal differentiation are carcinosarcomas and pulmonary
      blastomas. Tumors with analogous features are of ubiquitous distribution in the
      human body and have been described in numerous other organs, including the
      gastrointestinal tract, the genitourinary tract, and the endocrine system.
      Although the histopathologic features of these tumors may seem simple in most
      cases, there appear to be numerous pitfalls in their diagnosis; gray areas still
      remain in the characterization of these tumors, because a certain degree of
      overlap may be encountered with these two conditions. Such problems are
      understandable because the incidence of these tumors in the general population is
      very rare. Therefore, one is expected to find divergent points of view regarding
      these neoplasms. It is of importance, however, to unify criteria not only for
      diagnostic purposes, but also to determine the prevalence and behavior of these
      neoplasms, because such information may provide a rationale for adjustment and
      improvement in the treatment and diagnosis of these unusual neoplasms. We will
      review past and current concepts regarding these unusual tumors, as well as their
      more salient histopathologic features.

PMID- 7638447
TI  - Primary sarcomas of the lung.
AB  - Primary pulmonary sarcomas are rare tumors. Because the lung is one of the
      favored metastatic sites for soft tissue sarcomas, care must be taken when
      evaluating these lesions to rule out the possibility of an alternate primary
      source by means of thorough clinical history and radiographic evaluation. In
      addition to the difficulties involved in separating primary from metastatic
      tumors, pulmonary sarcomas must be distinguished from a number of sarcomalike
      primary lung neoplasms, including spindle and giant cell (pleomorphic) carcinoma,
      and from mixed epithelial/mesenchymal lesions such as pulmonary blastoma and
      carcinosarcoma. The criteria helpful for accomplishing this distinction are
      discussed, along with a review of primary sarcomas of the lung, with emphasis on
      clinicopathologic, immunohistochemical, and ultrastructural features that may be
      of aid for diagnosis. Additionally, recent or newly described entities are also
      discussed, and evolving concepts on the pathogenesis and terminology of these
      lesions are underscored.

PMID- 7638448
TI  - Pulmonary lymphoid disorders.
AB  - Organized lymphoid aggregates are normally found within the walls of bronchi in
      many species and may occur, under conditions of disease, in humans. This bronchus
      associated lymphoid tissue (BALT) can be viewed as an organizing principle to
      explain the behavior and distribution of many pulmonary lymphoid proliferations,
      both hyperplastic and neoplastic. The extent of lymphoid hyperplasia can vary,
      from multifocal proliferations that arise in and remain in the airway walls
      (follicular hyperplasia of BALT) to those that form a solitary mass or nodule
      (nodular lymphoid hyperplasia of BALT or "pseudolymphoma") to multifocal or
      diffuse lymphoid hyperplasia of BALT ("lymphoid interstitial pneumonitis"). It
      seems likely that more than one cause accounts for these proliferations. Of
      interest is the hypothesis that many examples of diffuse lymphoid hyperplasia
      associated with the acquired immune deficiency syndrome may have a viral cause,
      possibly human immunodeficiency virus or, in some cases, Epstein-Barr virus
      (EBV). Most pulmonary lymphomas are low-grade B cell lymphomas. They exhibit
      histological diversity in any given case, characterized by small lymphocytes with
      irregular nuclei and pale cytoplasm (so-called "centrocytelike" cells), scattered
      immunoblasts, and lymphoplasmacytic or plasma cells. Reactive germinal centers
      are frequently present, and this, along with the benign clinical behavior of
      these tumors, may cause diagnostic confusion with reactive lesions. Both the
      histological appearance and the clinical behavior (in particular, the tendency to
      recur in extranodal sites) of these low-grade lymphomas can be explained on the
      basis of origin in BALT. T cell lymphoproliferative processes can occur in the
      lung but are rare. Lymphomatoid granulomatosis (angioimmunoproliferative lesion)
      is an angiocentric and necrotizing, polymorphous lymphoid lesion that presents as
      multiple masses in the lung, involves skin and central nervous system (among
      other organs), may progress to histologically overt lymphoma, and is
      immunophenotypically predominantly a T cell process. Microscopically, a
      lymphohistiocytic infiltrate, including variable numbers of atypical cells, is
      present. Recent in situ hybridization and immunohistochemical studies have served
      to show EBV localized to the large cells. In addition, these atypical cells often
      show B cell immunophenotypic features and are present in a background of small,
      reactive T cells. It is therefore possible that lymphomatoid granulomatosis is a
      family of T cell rich lymphoproliferations driven by EBV infection of B cells
      and/or T cells, analagous to the EBV-associated, posttransplantation B cell
      lymphoproliferative disorders.

PMID- 7638450
TI  - Lung tumors of uncertain histogenesis.
AB  - Unusual lung tumors of uncertain origin have been described briefly concerning
      benign clear cell (sugar) tumor and, in more detail, concerning pneumocytoma (so
      called sclerosing hemangioma). Melanocytic differentiation of clear cell tumor,
      which is peculiar to the lung, has been suggested recently. Sclerosing
      hemangioma, also unique to the lung, is now considered to be a tumor (neoplasm)
      related to alveolar epithelial cells. It shows invasive growth and multiplicity
      (or aerogenous metastasis), but is very rarely capable of lymph node metastasis.
      It should be designated as pneumocytoma.

PMID- 7638449
TI  - Lung tumors derived from ectopic tissues.
AB  - Ectopic tissues rarely occur in the lung. They include endometriosis,
      neurological tissue, thyroid, pancreas, and adrenal. Choristomas are very rare
      developmental anomalies derived from these ectopic tissues. They develop as a
      mass composed of histologically normal tissues that are heterotopic in the lung.
      Various intrapulmonary neoplasms also rarely develop from ectopic tissues. They
      include malignant melanoma, thymoma, meningioma, glomus tumor, germ cell
      neoplasms (choriocarcinoma and teratoma), and ependymoma. The clinicopathological
      features of these unusual pulmonary neoplasms are discussed.

PMID- 7638451
TI  - Unusual manifestations of metastatic tumors to the lungs.
AB  - Because of the lung's rich capillary bed and central location in the circulatory
      system, this organ is one of the most frequent recipient sites for metastatic
      spread of disease. The histopathologic diagnosis in the vast majority of cases is
      straightforward and usually supported by clinical findings and a prior history of
      a known primary tumor elsewhere. However, unusual circumstances may arise: a
      primary tumor may remain occult at the time of pulmonary metastases, the
      metastasis may develop after a long period of latency, or the histopathologic
      appearance of the metastasis may assume a form that is uncharacteristic or
      inconsistent with the suspected primary lesion, which raises the possibility of
      the emergence of a second primary tumor in the lung. Herein we review a variety
      of unusual manifestations of metastatic disease to the lungs that may pose
      difficulties for diagnosis and interpretation. Emphasis is made on the
      histological differential diagnosis and the clues that may alert the pathologist
      to recognizing the process as metastatic in origin.

PMID- 7638452
TI  - Introduction to rehabilitation of neuromuscular disorders.

PMID- 7638454
TI  - The development of current approaches to the management of spinal deformity for
      patients with neuromuscular disease.
AB  - Special attention needs to be paid to the spine of a patient with a neuromuscular
      disorder. Spinal muscular weakness that causes progressive spinal collapse with
      resulting scoliosis, kyphosis, or kyphoscoliosis can lead to pain and difficulty
      in standing, walking, sitting, or balancing. Function and independence may be
      further lost. Appropriate measures, including spinal fusion in many instances,
      need to be undertaken as part of the overall care of the individual with
      neuromuscular disease.

PMID- 7638453
TI  - Nutritional rehabilitation in neuromuscular disorders.

PMID- 7638455
TI  - Spinal deformities and wheelchair seating in Duchenne muscular dystrophy: twenty
      years of research and clinical experience.

PMID- 7638456
TI  - Therapeutic interventions and habilitation considerations--a historical
      perspective from Tamplin to robotics for pseudohypertrophic muscular dystrophy.

PMID- 7638457
TI  - Evaluation and management of dysphagia.

PMID- 7638458
TI  - Assessment and management of communication impairment in neuromuscular disease.

PMID- 7638459
TI  - Psychologic considerations in the treatment of individuals with generalized
      neuromuscular disorders.

PMID- 7638460
TI  - Orthopedic approaches for the treatment of lower extremity contractures in the
      Duchenne muscular dystrophy patient in the United States and Canada.

PMID- 7638461
TI  - Psychosocial considerations in the sexual rehabilitation of individuals with
      neuromuscular disease.

PMID- 7638462
TI  - Respiratory muscle aids for the prevention of pulmonary morbidity and mortality.
AB  - The great majority of individuals with ventilatory failure due to paralytic
      syndromes can be managed entirely by noninvasive inspiratory and expiratory
      muscle aids. When the equipment is properly used, individuals may eventually
      become dependent on noninvasive IPPV 24 hours a day without ever being
      hospitalized, intubated, tracheostomized, or bronchoscoped. The use of
      noninvasive respiratory muscle aids eliminates the need for "crisis" decision
      making about whether or not to "go on a respirator." Use of respiratory muscle
      aids by ALS patients familiarizes them with ventilator dependency before any
      decision about tracheostomy needs to be made. These methods enhance quality of
      life in many ways, including permitting the use of GPB for security in the event
      of ventilator failure. They can also drastically decrease cost and optimize
      psychosocial functioning. These techniques should become part of the therapeutic
      armamentarium of every physician who treats patients with generalized
      neuromuscular disorders who have the potential to develop ventilatory
      insufficiency, mucus plugging, or both.

PMID- 7638463
TI  - Alternative techniques for managing acute neuromuscular respiratory failure.

PMID- 7638465
TI  - Dilated cardiomyopathy of muscular dystrophy: a multifaceted approach to
      management.

PMID- 7638464
TI  - Early treatment to preserve quality of locomotion for children with Duchenne
      muscular dystrophy.

PMID- 7638466
TI  - Cardiovascular considerations in the management of neuromuscular disease.

PMID- 7638468
TI  - Endorectal coil magnetic resonance imaging of prostate cancer.

PMID- 7638467
TI  - Monoclonal antibody imaging of recurrent and metastatic prostate cancer.
AB  - In summary, this agent is safe for administration and more accurate than any
      currently available imaging modality for the detection of extraprostatic
      metastases. This agent is still under investigation and some day may aid
      urologists in the evaluation of prostate cancer by improving preoperative staging
      and demonstration of advanced disease and postoperative localization of recurrent
      disease. Improved staging and localization will reduce unnecessary tests and
      treatment that will lead to reduced morbidity, better management, earlier
      detection, and intervention in advanced disease and improved cost-effectiveness.

PMID- 7638469
TI  - Chemoprevention of prostate cancer.

PMID- 7638470
TI  - Early intervention or expectant management for prostate cancer. The Prostate
      Cancer Intervention Versus Observation Trial (PIVOT): a randomized trial
      comparing radical prostatectomy with expectant management for the treatment of
      clinically localized prostate cancer.

PMID- 7638471
TI  - Reducing length of stay after radical prostatectomy.

PMID- 7638472
TI  - Role of induction androgen deprivation before radical prostatectomy.

PMID- 7638473
TI  - Cryosurgical ablation for prostate cancer: a current review.
AB  - The available data on the efficacy of cryosurgery are still too immature to
      recommend this as a comparable option to radical surgery in the younger patient
      (< 72 years old) with organ-confined disease and at least a 10- to 15-year life
      expectancy. The available 3-month and 1-year positive biopsy figures of 10% to
      20% are inversely comparable to the 10-year 80% to 90% disease-free survivals in
      contemporary radical prostatectomy series. While we wait for survival data to
      mature, it is unlikely that 10% to 20% local recurrence rates will translate into
      80% to 90% disease-free survival rates. Only the data from the Crittendon
      Hospital group, which reports positive biopsies at 1 year of 3% to 4%, deserves
      special attention. Their protocol of optimal presurgical androgen ablation, use
      of thermosensors, and use of 2 to 3 freeze cycles may direct the way to a better
      cryosurgical technique. Conversely, the 2 to 8 months of presurgical androgen
      deprivation may just be prolonging the appearance of cryo-resistant cells.
      Regarding clinical stage C disease, the data looks promising with similar results
      as in organ-confined disease with a 10% to 20% positive biopsy rate at 3 months.
      One has to be cautious about what is really a stage C lesion, and comparison of
      preoperative PSA values enhance the comparisons between series. Overall, if the 1
      year local recurrence rate does not exceed 30%, recommending cryosurgery as a
      viable option seems reasonable.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7638474
TI  - New treatment strategies for hormone refractory prostate cancer.

PMID- 7638475
TI  - The molecular staging of prostate cancer.

PMID- 7638476
TI  - Measurement of subcellular Ca2+ redistribution in cardiac muscle in situ: time
      resolved rapid freezing and electron probe microanalysis.
AB  - To directly assess the physiological roles of sarcoplasmic reticulum (SR) and
      mitochondria (MT), we have utilized energy dispersive electron probe
      microanalysis (EPMA) on ultrathin freeze-dried cryosections from isolated
      papillary muscles, rapidly frozen at precise time points of the contractile
      cycle. Using this approach, we can detect redistribution of subcellular Ca2+
      during the cardiac contractile cycle. Changes in Ca2+ of less than 1.0 mmol/kg
      dry wt can be detected. By determining the variability of the Ca2+ measurements
      in preliminary experiments, we have also demonstrated that it is possible to
      optimize experimental design, i.e., to predict the number of animals per
      treatment group and the number of X-ray spectra per animal that are required in
      order to detect a specified Ca2+ difference. Quantitative EPMA of rapidly frozen
      contracting papillary muscle has also allowed us to correlate the Ca2+ content of
      SR and MT with the contractile state of the muscle. Our results show a decrease
      of 40% in the amount of Ca2+ stored in the junctional SR during a cardiac muscle
      twitch, thus providing direct evidence for a role of the SR as a primary site of
      Ca2+ release. In addition, we have demonstrated dissociation between MT Ca2+
      uptake and activation of regulatory enzymes, such as pyruvate dehydrogenase,
      indicating that MT Ca2+ uptake is not required for activation of MT metabolism.

PMID- 7638477
TI  - 12th Pfefferkorn Conference on The Science of Biological Microanalysis.
      Proceedings. Cambridge, United Kingdom, September 27-30, 1993.

PMID- 7638480
TI  - Electron probe X-ray microanalysis of epithelial cells: aspects of cryofixation.
AB  - Content and distribution of diffusible ions in epithelial cells were studied by
      scanning transmission electron microscopy and energy dispersive electron probe X
      ray microanalysis of freeze-dried cryosections from trout kidney, rat liver and
      Malpighian tubules of Drosophila larvae. Cryofixation of small excised kidney and
      liver samples by rapid immersion into liquid propane resulted in intracellular
      K/Na-ratios < 1. In contrast, K/Na-ratios > 7 were obtained after in situ
      cryofixation by means of a cryopunching device which allows tissue pieces to be
      frozen during excision from the intact organ. Isolated hepatocytes cryofixed in a
      small droplet of culture medium had a K/Na-ratio of 3.7. After culturing the
      hepatocytes, the K/Na-ratio increased to 24. Effects of extracellular media of
      different composition on the intracellular element content were studied.
      Malpighian tubules of Drosophila larvae were cryofixed by rapid immersion into
      liquid propane, and the distribution of K across the cells forming the tubules
      from the basal to the apical cell membrane was measured. An increasing K gradient
      was found from the intermediate to the apical cytoplasm. The intracellular K
      distribution was dependent on ions and transport inhibitors present in the fluid
      surrounding the Malpighian tubules within the larvae. Content and distribution of
      ions in epithelial cells sensitively depend on the physiological state
      immediately before cryofixation. Thus, electron probe X-ray microanalysis of
      cells and cell functions requires careful selection and control of the cell
      system to be studied.

PMID- 7638478
TI  - Quantitative biological electron probe microanalysis with a wavelength dispersive
      spectrometer.
AB  - This paper describes the details of quantitative electron probe microanalysis
      (EPMA) performed with a wavelength dispersive spectrometer (WDS). EPMA was
      carried out on the giant neuron of a fresh frozen ganglion from the snail Lymnaea
      stagnalis. The freeze-dried cryosections were compared with sections of freeze
      dried, embedded tissue. It was found, that in the ganglion there are two kinds of
      neurons with a different chlorine concentration of 11 mmole/liter and 32
      mmole/liter. Isolated neurons in culture were shown to differ in elemental
      composition from those in the ganglion tissue.

PMID- 7638479
TI  - Use of in vitro systems for X-ray microanalysis.
AB  - The use of X-ray microanalysis in human pathology may require the use of
      cryoprepared tissue. Often it is impossible to carry out freezing of the tissue
      in an optimal way, and in addition, it is difficult to carry out experiments in
      living patients. The use of in vitro systems and cell cultures allows separation
      of the process of tissue removal and the freezing procedure, and also makes
      testing of pharmacological or toxic substances possible. In experiments with
      animal tissue it was shown that incubation in a physiological buffer induced
      significant changes in the concentrations of Na, K, and Cl. In general, the
      concentrations of Na and Cl increased, those of K decreased. Prolonged incubation
      of brain tissue (cortex and hippocampus) and of liver resulted in further changes
      of the cellular ion contents in the same direction. Incubation of pancreas and
      submandibular gland resulted in a limited reversal of the changes induced by
      dissection. The submandibular gland in vitro showed the same response to
      cholinergic stimulation as the gland in situ. The use of cell cultures for X-ray
      microanalysis is briefly reviewed and illustrated by an example of analysis of an
      immortalized sweat gland cell line. It was shown that these cells respond to
      stimulation by cAMP with loss of Cl and that this response was unaffected by the
      type of substrate the cells were grown on.

PMID- 7638481
TI  - The preparation of cultured cells for X-ray microanalysis.
AB  - X-ray microanalysis of cells in culture is being used increasingly for the study
      of relationships between element (ion) content and cell function. There is,
      however, no one single method which can be used for the preparation of all
      different cell types for study by microanalysis. Cells in suspension are usually
      concentrated by centrifugation, before cryofixation, cryosectioning, and freeze
      drying. On the other hand cells grown as monolayers are more often studied as
      whole cell mounts, which are washed to remove the external medium before
      cryofixation and freeze drying. The alternative approach, sectioning of cell
      monolayers is rarely used. Some of the difficulties encountered in preparing and
      monolayers of smooth muscle cells for X-ray microanalysis are discussed here.

PMID- 7638482
TI  - Quantitative dark-field mass analysis of ultrathin cryosections in the field
      emission scanning transmission electron microscope.
AB  - The availability of a cryotransfer stage, highly efficient electron energy loss
      spectrometers, and ultra-thin-window energy-dispersive x-ray spectrometers for
      the VG Microscopes HB501 field-emission scanning transmission electron microscope
      (STEM) provides this instrument with the potential for high resolution biological
      microanalysis. Recent technical advances offer cryosections that are thin enough
      to take advantage of the analytical capabilities of this microscope. This paper
      first discusses the quantitative characterization of freeze-dried, ultrathin
      cryosections of directly frozen liver and brain by low-dose dark-field STEM
      imaging. Such images reveal high-quality sections with good structural detail,
      mainly due to reduced preparation artifacts and electron beam damage. These
      sections are thin enough for dark-field mass analysis, so that the mass of
      individual organelles can be measured in situ, and their water content deduced.
      This permits the measurement of mass loss-corrected subcellular elemental
      concentrations. The results suggest several new applications for cryosections as
      illustrated by data on synaptic activity-dependent calcium regulation in Purkinje
      cells of mouse cerebellum. Low-dose mass analysis of cryosections in combination
      with x-ray and electron spectroscopy is a promising approach to quantitating
      physiological changes in mass distribution and elemental composition.

PMID- 7638484
TI  - X-ray microanalysis of endocrine, exocrine and intestinal cells and organs in
      culture: technical and physiological aspects.
AB  - In the present study methods for preparation of cultured cells and organ cultures
      for analytical electron microscopy are investigated. These methods allow
      qualitative and quantitative analysis of mobile ions in combination with
      biochemical or morphological studies. Cultured cells can be easily prepared for
      analytical microscopy and therefore use of in vitro systems for X-ray
      microanalysis has increased over the last few years. Two major, anhydrous
      preparation techniques, by which loss or redistribution of ions is minimized,
      were used: (1) Cells were cryosectioned and analysis carried out on freeze-dried
      sections obtained from frozen cell monolayers, pelleted cells or organ cultures.
      (2)Cells cultured on supports compatible with elemental analysis were frozen
      after removal of experimental media by rinsing, freeze-dried and analyzed. The
      first technique was applied to the studies of the elemental content of isolated
      Langerhans islets and thyroid follicles cultured in collagen gel. The second was
      used in studies of the ionic changes in enterocytes. Data obtained from
      organotypic cell cultures and cultures of single cells were compared with
      analytical data obtained from sections of corresponding tissues, where isolation,
      culturing and steps in processing such as removal of culture or experimental
      medium were omitted. It was shown that often culture systems fully acceptable to
      physiologists have an elemental composition different from that of tissue in situ
      and can not be regarded as fully normal tissue.

PMID- 7638485
TI  - Standardless analysis of biological tissue sections.
AB  - The X-ray microanalysis of thin biological samples which are usually supported on
      a thin organic film or are self-supporting specimens, has required the use of
      standards which contain the elements of interest. Spectra from the standards are
      used to calculate the factors for converting X-ray data recorded on the specimen
      into elemental concentrations. A method is discussed here, in which these factors
      are evaluated from formulae. The most important physical process to be evaluated
      is that of characteristic X-ray production in the specimen. The bremsstrahlung
      production must also be evaluated if the Hall or continuum normalisation (CN)
      method of quantitation is to be used. This paper discusses briefly methods of
      calculating values for the X-ray production cross-sections for both
      characteristic and bremsstrahlung radiation. The way in which these are
      incorporated into standardless quantitation methods for biological samples is
      described. Calculations of some cross-section data are presented for typical
      analytical conditions.

PMID- 7638483
TI  - Electron microprobe analysis of electrolytes in whole cultured epithelial cells.
AB  - Microprobe analysis was used to determine electrolyte contents in whole
      epithelial sheets of A6 cells and to investigate the most critical points of this
      method. Analysis of dextran standard sections of different thickness revealed
      that low accelerating voltages of about 10 kV are best suited for whole freeze
      dried cells on thick supports, since 5 microM thick sections are not penetrated
      by 10 kV electrons. Washing of A6 cells for 10 sec with distilled water led to
      cell swelling of about 40%, but the molar concentration ratios and the
      concentrations per dry weight (dw) were not altered. Washing for 60 sec with
      distilled water caused a further increase in cell volume (120%) and loss of
      cellular K and Cl (90 mmol/kg dw). Washing with isotonic NH4- acetate led to a
      loss of cell Cl already after 10 sec. To characterize the Na transport
      compartment, A6 cells cultured on permeable supports were washed for 5 sec with
      distilled water, freeze-dried, and analyzed. Inhibition of transepithelial Na
      transport by ouabain increased Na/P from 0.15 +/- 0.07 to 0.75 +/- 0.03 and Cl/P
      from 0.21 +/- 0.001 to 0.38 +/- 0.003 while K/P decreased from 0.83 +/- 0.08 to
      0.32 +/- 0.03. The changes in cell Na and K contents can be explained by K/Na
      exchange; the increase in Cl content indicates some cell swelling. Since the
      ouabain-induced changes could be prevented by apical amiloride, the apical
      membrane provides the most important pathway for Na entry in A6 cells.

PMID- 7638486
TI  - Standards for X-ray microanalysis of calcified structures.
AB  - The ability of electron probe X-ray microanalysis (EPMA) to solve biological
      problems often depends on the use of a quantitative approach. EPMA allows the
      quantitative determination of chemical elements of biological materials by using
      reference standards which resemble the specimen in the mode of interaction with
      the electron beam. Although there is a large experience in the quantification of
      elements in biological thin specimens, experience with standards for X-ray
      microanalysis of bulk specimens is limited, especially for calcified structures
      where the density of the specimen is difficult to estimate. The quality of the
      results in EPMA depends on obtaining accurate calibration curves which allow the
      establishment of the relationship between the signal measured and the
      concentration of the element of interest. The different methods for specimen
      preparation and the thickness of the specimen will also determine the precise
      nature of the standardization technique to be adopted. The physics of the
      electron beam-specimen interactions impose limitations upon the accuracy of
      calibration, and the choice of an unstable standard can result in large errors in
      the quantification of elements. We have reviewed the different types of compounds
      that have been used as standards for biological EPMA of thin and bulk specimens
      and discuss their potential use for quantitative analysis of mineralized tissues,
      with special reference to otoconia, the calcified structures of the vestibular
      system.

PMID- 7638488
TI  - Data handling in quantitative microanalysis in biology.
AB  - In cell biology, electron probe X-ray microanalysis can reveal the distribution
      of chemical elements inside a single cell. The full description of a biological
      system (cell population, tissue) requires a great number of spot measurements. In
      quantitative analysis, the measurements are subject to experimental errors of
      several types; moreover, the relations between the resulting values are usually
      more interesting than the absolute concentrations. Nevertheless, the proper
      evaluation of quantitative values can discover information more on the object of
      study. A system of simple statistical tests is suggested here which can solve
      several problems. Some concentration values can be far from the statistical
      average due to errors in measurement; therefore, a statistical test of
      plausibility of the measured values is carried out. In the compartments (e.g.,
      nucleus, cytoplasm or other selected areas), the distribution of an element can
      be nonhomogeneous, and hence a statistical test of homogeneity of the element
      distribution in specified areas is provided. The tests continue with a test for
      correlation, in which the concentrations of a given element in a pair of
      specified areas are compared. These test proceed step-by-step for all elements of
      interest. Subsequently, the relations of concentrations in all possible pairs of
      elements in the area in question are calculated. Moreover, cells within a
      population can be different from the point of view of elemental concentration; a
      statistical test of homogeneity of the cell population is provided. In the case
      of nonhomogeneity, the concentration values and/or cells within a population are
      clustered into homogeneous groups. The evaluation is carried out automatically,
      with a simple program. The system of programs, in which the program for
      evaluation is incorporated, is included semi-on-line in the EDAX9900 system,
      where the measurement and evaluation are carried out in sequence. The results for
      a population of Streptomyces aureofaciens are shown as an example.

PMID- 7638489
TI  - X-ray microanalysis with the environmental scanning electron microscope:
      interpretation of data obtained under different atmospheric conditions.
AB  - X-ray microanalysis of non-biological and biological specimens was carried out in
      an environmental scanning electron microscope (ESEM) over a range of atmospheric
      conditions. Introduction of water vapour into the specimen chamber lead to direct
      X-ray contribution from oxygen atoms, an increase in extraneous background
      (causing reduced P/B ratios of other elements), X-ray absorption (also reducing
      P/B ratios) and broadening (skirting) of the electron beam. Similar results were
      obtained after introduction of an argon atmosphere. These effects were reduced
      under conditions of minimal chamber atmospheric pressure and maximal accelerating
      voltage. Because of beam skirting, quantitative X-ray microanalysis of biological
      specimens in a water vapour atmosphere was only valid where the sample was spread
      over a wide area (leading to mean elemental values for the whole preparation).
      Unless appropriate correction factors or changes in instrumentation can be
      implemented, quantitative analysis of wet specimens in ESEM cannot be applied to
      discrete specimens or to limited areas within a mixed sample.

PMID- 7638487
TI  - Light element X-ray microanalysis in biology.
AB  - It is shown that both qualitative and quantitative light element X-ray
      microanalysis of biological samples is feasible. These analyses were carried out
      using ultrathin window (UTW) detectors. Quantitative analysis yields a total
      element analysis with H estimated by difference or "guesstimated". Comparison
      with calculated concentrations, or concentrations obtained by chemical analysis,
      shows that X-ray microanalysis of sections, by the peak to continuum ratio model,
      give sufficiently accurate results for biological purposes. The measurement of O
      concentrations to yield water content is carried out using x-ray imaging
      techniques, so that the distribution of heavier elements can be spatially related
      to water and dry mass distribution. Similarly light element and heavy/light
      element ratios are readily visualised by X-ray imaging. These ratios can indicate
      the subcellular distribution of different molecular species e.g., nitrogenous
      compounds such as urates. It is possible to derive quantitative images of water
      distribution in both sections and bulk samples. Comparisons of the same sample
      type both as frozen sections and frozen bulk samples show that the water
      estimates obtained by the two different analytical methods are similar. Oxygen
      analysis of C films at different specimen temperatures unequivocally reveals the
      temperature at which ice deposition on the specimen commences. This establishes
      safe conditions for reducing mass loss in model samples and freeze-dried sections
      to minimal levels and for avoiding artefactual oxygen analyses of both frozen
      hydrated and freeze-dried sections.

PMID- 7638490
TI  - Biological electron energy loss spectroscopy in the field-emission scanning
      transmission electron microscope.
AB  - The dedicated scanning transmission electron microscope (STEM) combined with
      parallel electron energy loss spectroscopy (EELS) provides a very sensitive means
      of detecting specific elements in small structures. EELS is more sensitive than
      optimized energy-dispersive X-ray spectroscopy by a factor of about three for
      calcium. Measurement of such low concentrations requires special processing
      methods such as difference-acquisition techniques and multiple least squares
      procedures for fitting reference spectra. By analyzing data recorded at each
      pixel in a spectrum-image it is possible to map quantitatively the elemental
      distributions in a specimen. It is possible to prepare cryosections that are
      sufficiently thin to avoid excessive plural inelastic scattering so analysis can
      be performed at 100 keV beam energy. Under optimal conditions, a resolution of 10
      nm and detection limits of a few atoms are achievable for elements such as
      calcium, phosphorus and iron. In the field emission STEM certain types of
      chemical information can be extracted from biological specimens. Valence EELS has
      been exploited to measure water distributions in frozen hydrated cryosections.

PMID- 7638491
TI  - Changes of ion and water content of mouse intestinal cells after pilocarpine and
      isoproterenol stimulation.
AB  - Cytoplasmic monovalent ion and water contents in morphologically defined mice
      jejunal cells were measured by X-ray microanalysis in order to gain insight into
      the cell-type specificity of intestinal electrolyte transport mechanisms. Ion and
      water contents were measured independently. It was found that in some cases net
      fluxes of ions and water do not correspond to the assumption of constant osmotic
      activity of cytoplasmic Na and K ions. Stimulation of secretion with the
      cholinergic secretagogue pilocarpine resulted in efflux of Cl- from an influx of
      K+ into crypt enterocytes containing small secretion granula (crypt A cells). No
      significant changes in ion concentrations were found in crypt enterocytes without
      secretion granula (crypt B cells). Crypt A cells were more likely to be
      stimulated by pilocarpine than crypt B cells, and the basolateral K+ efflux
      pathway in crypt A cells appeared to be rate-limiting. In villus enterocytes,
      pilocarpine stimulated Cl- efflux. Isoproterenol caused marked changes in the
      cytoplasmic Cl content of all epithelial cells. These changes were reversed by
      inhibition of adenylate cyclase by alloxan, with the sole exception of Cl
      increase in villus absorptive cells. The results are consistent with an cAMP
      mediated stimulated secretion in crypt epithelial cells and a predominantly cAMP
      independent stimulation of absorption in villus cells. The results obtained
      suggest a transcellular route of Cl absorption in the mouse jejunum.

PMID- 7638492
TI  - Energy-filtering transmission electron microscopy as a tool for structural and
      compositional analysis of isolated ferritin particles.
AB  - Structural and compositional analysis of isolated horse-spleen ferritin particles
      was performed by energy filtering transmission electron microscopy (EFTEM).
      Ferritin particles were collected in ultrathin (2 nm thick) chromium films and
      analyzed without any additional stain by electron energy-loss spectroscopy (EELS)
      for iron and carbon and by electron-spectroscopic imaging (ESI) for carbon. The
      ultrastructure of the proteinaceous shell of the ferritin particle, as obtained
      by the carbon net-intensity electron spectroscopical and carbon concentration
      distribution images, was qualitatively compared to the structure as acquired by a
      negative-staining procedure. Quantitative analysis of the number of carbon atoms
      in the ferritin-shell proteins was carried out through an ESI-acquisition
      protocol and processing procedure with calibrated attenuation filters in the
      optical path to the TV camera. This procedure included images acquired with
      calibrated attenuation filters for the compensation of shading and the non-linear
      performance of the TV camera used in the analytical part of the procedure. A new
      ?ESI-Spectra? program is proposed that allows element-related spectra to be
      generated at any place and with any frame size in a contrast-sensitive or other
      type of image present on the computer monitor screen.

PMID- 7638493
TI  - Image-EELS: a synthesis of energy-loss analysis and imaging.
AB  - Two different modes of energy-filtering transmission electron microscopy (EFTEM)
      are often used for element microanalysis: electron energy-loss spectroscopy
      (EELS) and electron spectroscopic imaging (ESI). A new approach was developed
      which we call Image-EELS. This procedure was realized with the commercially
      available standard equipment of the energy-filtering transmission microscope CEM
      902 (Zeiss, Germany). A series of energy-filtered images is recorded with ESI at
      many different energy losses. In a second step the intensity of selected objects
      is measured for each energy loss and plotted as a function of the energy loss,
      that means as an EELS spectrum. This method increases the sensitivity of EELS
      analysis, especially for very small and irregular objects, because the lateral
      resolution is enhanced and the noise is suppressed by the integration of many
      pixels belonging to one type of object. Many spectra can be calculated from one
      image series, enabling the comparison of spectra from different objects. Selected
      images from the series can be used for ESI elemental mapping, so that errors and
      limits in the different mapping procedures can be detected. Image-EELS is a
      synthesis of EELS and ESI and as such it constitutes a considerable progress for
      element microanalysis with EFTEM, not only for biological objects.

PMID- 7638494
TI  - The principles of proton probe microanalysis in biology.
AB  - The proton microprobe, more correctly described as an ion microprobe which
      operates at MeV energies, complements its parent instrument the electron
      microprobe. This paper compares the basic principles and performance of the two
      instruments and relates the evolution of biological analysis on such ion
      microprobes to that on electron microprobes, covering the development of sample
      handling techniques and of data handling techniques and comparing beam damage
      studies. The paper describes the variety of techniques available to the ion
      microprobe - the initial techniques of Energy Dispersive X-ray analysis,
      Rutherford Back Scattering and Nuclear Reaction Analysis and the rapid evolution
      of new techniques, from Scanning Transmission Ion Microscopy to 3-dimensional
      tomography. All of these new techniques required the advanced computerised data
      handling which has been a feature of ion microprobe development.

PMID- 7638495
TI  - New applications of the nuclear microprobe for biological samples.
AB  - The continuing development of the Nuclear Microprobe (NMP) has opened up new
      fields of applications in biology and medicine. Quantitative multielemental
      analysis in small sections of samples can be performed routinely. The use of
      techniques such as scanning transmission ion microscopy makes imaging as well as
      mass normalization possible at submicron resolution. Recent medical applications
      include studies on thin cryosections prepared from autopsies and biopsies, as
      well as single cells grown directly on the backing foil used in the NMP analyses.
      The purpose of the single cell analysis is often pharmacological, e.g., testing
      of new drugs, their uptake and distribution. New applications, for instance, in
      food chemistry, ecology and evolutionary genetics, are also taking advantage of
      the high analytical sensitivity of the NMP in combination with its imaging
      capability.

PMID- 7638496
TI  - Proton-induced and electron-induced X-ray microanalysis of insulin-secreting
      cells.
AB  - Elemental redistribution induced by insulin secretion, was investigated by
      electron and proton probe X-ray microanalysis. In particular, ion fluxes
      following immediately upon stimulation were studied. As the sensitivity of the
      electron probe was insufficient, the proton microprobe was employed. In order to
      see whether the cell is asymmetric with respect to Ca2+ influx, the cells were
      stimulated in the presence of Sr2+ (as a Ca2+ analog). Insulin-secreting cells
      (RINm5F cells and isolated mouse beta-cells) were cultured on grids and shock
      frozen at 2-30 seconds after stimulation. In a large number of cells, the major
      elements and and large fluxes were analyzed by the electron microprobe. In the
      proton microprobe, selected cells were analyzed and elemental maps were compared
      with electron micrographs of the same cells. The proton microprobe, but not the
      electron microprobe, could detect an influx of Sr in response to K+-stimulation
      for 2 seconds, in RINm5F cells. No polarization of Sr2+ uptake in RINm5F-cells
      could be detected, and the beta-cells did not respond to high K+ by uptake of Sr.
      Momentary stimulation of beta-cells also resulted in a significant increase in
      Na, detected by the electron probe. Spreading of the beta-cells on the substrate
      appears to influence the subcellular elemental distribution. Thus, the proton
      probe has potential to detect small changes in elements such as those occurring
      after short-time stimulation.

PMID- 7638497
TI  - Laser microprobe mass spectrometry in biology and biomedicine.
AB  - An overview is given of laser microprobe mass spectrometry (LMMS) in biology and
      biomedicine (1989-1993). The present instrumentation and its analytical features
      are surveyed. Applications are presented with special attention on human and
      animal tissue samples, as well as plant material. The capabilities of LMMS to
      study the element distribution in histological sections, to identify the chemical
      composition of inorganic inclusions and to generate structural information from
      organic compounds are evidenced.

PMID- 7638498
TI  - Ion microscopy in biology.
AB  - Ion microscopy, a mass spectrometry based isotopic imaging technique, is uniquely
      suited for ion transport related problems in biological systems. Due to its high
      sensitivity, it can image the transport and distribution of both major and minor
      elements (isotopes) at subcellular resolutions. The images of major elements such
      as K, Na, CI, etc., can be viewed directly and recorded in real-time from the
      microchannel plate-fluorescent screen detector of the instrument. The low
      concentration physiologically important elements, such as Ca, need about one
      minute of integration for good quality imaging. The isotopic imaging capability
      of ion microscopy provides a unique approach for the use of stable isotopes as
      tracers. In this way, one can image both the endogenous and the transported
      isotopes independently. Strict cryogenic sample preparations are essential for
      ion transport studies. Correlative imaging of the same cell with laser scanning
      confocal microscopy and ion microscopy can positively identify smaller
      cytoplasmic compartments such as the Golgi apparatus in calcium images. We have
      identified the Golgi apparatus as a calcium storing organelle. Another unique
      application of ion microscopy is the imaging of boron from boronated drugs used
      in Boron Neutron Capture Therapy (BNCT) of cancer. Ion microscopy is capable of
      rapid screening of potential drugs for BNCT. This critical information is
      essential for the fundamental understanding of BNCT. Ion microscopy is now at the
      stage where it can provide previously unattainable answers to important
      biomedical questions.

PMID- 7638499
TI  - An X-ray microanalytical study on the effects of ouabain and N-ethyl maleimide on
      the elemental concentrations in Malpighian tubule cells of Locusta.
AB  - X-ray microanalysis was used to study elemental distribution in Malpighian tubule
      cells of Locusta migratoria and how these are affected by the replacement of
      bathing medium K+ with Rb+ and by inclusion of the transport inhibitors ouabain
      and n-ethyl maleimide (NEM) in standard (K+-containing) and Rb+-Ringer (K+-free)
      solutions. Incubation of tubules in standard Ringer containing 1mM ouabain
      dramatically affected the intracellular levels of K and Na. The intracellular K
      concentration fell and Na concentration increased in all regions studied. Despite
      this, a gradient of increasing K concentration from basal to apical cell surface
      was maintained. Ouabain also reduced the intracellular levels of Rb when applied
      in Rb+-Ringer. Cl and P levels were unaffected by ouabain treatment. Incubation
      in standard and Rb+-Ringer solutions containing 1 microM NEM caused a significant
      increase in intracellular K levels in all regions of the cell compared with that
      observed in the absence of NEM. Rb levels were little affected by NEM except in
      the apical cytoplasm and microvillar regions where they were significantly
      reduced compared with Rb+-Ringer controls. NEM effected a significant increase in
      cellular levels of Na under Rb+-Ringer conditions. Intracellular Cl and P were
      not significantly affected by NEM. These results are discussed in relation to
      proposed mechanisms for the transport of ions and water across this secretory
      epithelium, with particular emphasis on the role of K+ as the 'prime mover' in
      this process.

PMID- 7638500
TI  - Optical methods for imaging ionic activities.
AB  - Optical fluorescence is characteristic of molecules and their environment, and
      dyes can be made whose fluorescence is altered by reversible binding to specific
      ions. By introducing these into the cytosol, fluorescence microscopy can be used
      to form dynamic images of ionic activities in living cells under experimental
      manipulation. Optical fluorescence spectra are broad-band, and if specific ion
      binding alters the wavelength of maximal excitation or emission, quantitative
      measurements can be made from the ratio of images taken at two different
      wavelengths, eliminating errors due to spatial variations in dye concentration
      and optical path-length. This method is analogous to continuum normalisation in X
      ray microanalysis, and is implemented using a sensitive video camera and computer
      processing digitised images. Fluorescent indicators exist for calcium, magnesium,
      hydrogen, sodium, zinc and chloride ions. Most imaging work has been on calcium,
      which is important in many cell signalling processes, and several calcium
      indicators are available with different spectral properties. Spatial resolution
      is limited to a few micron by out-of-focus blur, but repeated images can be
      captured with a time resolution as low as 200 msec, and by using dyes with high
      binding affinity, detection limits can be lower than by X-ray methods. There is a
      large and fast-growing literature of applications to many plant and animals cell
      types.

PMID- 7638501
TI  - A new versatile system for freeze-substitution, freeze-drying and low temperature
      embedding of biological specimens.
AB  - A universal system for freeze-substitution (FS), freeze-drying (FD) and low
      temperature embedding (LTE) has been developed, suited to perform standardized
      procedures of cryoprocessing biological and medical specimens as well as
      systematic studies of dehydration and embedding at various low and high
      temperatures. In a 35 1 Dewar vessel with 110 mm neck diameter an aluminum tube
      is mounted to the bottom of the liquid nitrogen (LN2x) reservoir and extends to
      the lower part of the cylindrical neck. At its top an aluminum plate serves as a
      contact surface for either the FS chamber or the FD chamber. Fs and subsequent
      LTE are carried out in an environment of dry cold nitrogen gas provided by
      evaporating nitrogen from the dewar. Different capsules and moulds may be used
      for cryodehydration and LTE. FD of bulk specimens or cryosections takes place in
      an absolutely clean vacuum provided by a cryosorption pump integrated in the FD
      apparatus. Most of the H2O molecules from the frozen specimen are trapped by
      large cold surfaces inside the drying chamber. Due to the low LN2 consumption
      during FS or FD (3-4 1 LN2/day) both procedures may be carried out for 8-10 days
      without refilling the dewar. A few representative results show that well frozen
      biological material is stabilized by prolonged FS or FD at temperatures of about 
      80 degrees C without user of chemical fixatives like OsO4 in the substitution
      medium during FS or by OsO4 vapor fixation after FD.

PMID- 7638502
TI  - Optimal freeze-drying of cryosections and bulk specimens for X-ray microanalysis.
AB  - Electron microscopic investigations of rapidly frozen specimens of striated
      muscle, either frozen-hydrated or obtained after different dehydration
      procedures, have shown that the subcellular distribution of the main cellular
      cation K+ or its surrogates Rb+, Cs+, or Tl+ does not follow the water
      distribution but follows certain proteins. Conflicting results obtained by X-ray
      microanalysis of freeze-dried cryosections are explained by showing that freeze
      drying of bulk specimens and cryosections must be carried out for rather long
      periods at low temperature in order to avoid severe shrinkage and ion
      redistribution artefacts. Proposals for future freeze-drying studies are derived
      from the concept that cellular water is organized differently from normal free
      water and that proteins of living cells are able to selectively adsorb alkali
      metal ions.

PMID- 7638503
TI  - Improvements in biological X-ray microanalysis: cryoembedding for specimen
      preparation and multivariate statistical analysis for data interpretation.
AB  - For biological X-ray microanalysis, cryoembedding (CE) combined with cryofixation
      (CF) and cryodehydration (CD) was already proposed as an alternative method to
      freeze-dried cryosections in 1984 by Wroblewski and Wroblewski. CD by freeze
      drying (FD) is usually recommended because it provides better retention of
      diffusible elements. CD by freeze-substitution (FS) has the advantage of being
      simpler, giving more reproducible preservation of ultrastructure and causing
      fewer problems for resin infiltration. We have increased the retention of
      diffusible elements by using home-made devices for CS and CE in the new Lowicryl
      K11M and HM23 resins. These resins allow samples to be kept at a maximum
      temperature of 213K and 193K respectively. Application of multivariate
      statistical analysis (MSA) to X-ray data (spectra and maps) allows the study of
      correlations between the analyzed elements in different nuclear areas and in the
      cytoplasm. The "factorial" images, obtained with MSA, display the compartments of
      strong correlation between P and K (nucleic acids) and the compartments of strong
      correlation between S and K (proteins). We suggest that the future application of
      MSA methods will provide increased knowledge of the physio-pathological
      compartmentation of diffusible elements at the subcellular level.

PMID- 7638504
TI  - Frontiers in head and neck oncology. Introduction.

PMID- 7638506
TI  - Management of the mandible in oral cancer.
AB  - Modern head and neck surgery has focused on patient rehabilitation and
      restoration of form and function in the treatment of oral cancers. An important
      aspect of that process has been the conservation of the mandible in tumor
      ablation and the reconstruction of the mandible if segmental resection is
      indicated. This article outlines the science and clinical data behind rim
      mandibulectomy and the mandibular osteotomy and "swing" to gain access to tumors
      of the posterior tongues and pharynx. Additionally, the various methods of
      reconstruction of the mandible in use today as well as the advantages and
      disadvantages of each are addressed.

PMID- 7638507
TI  - Advances in osseointegrated implants for dental and facial rehabilitation
      following major head and neck surgery.
AB  - Osseointegrated implants can be used to facilitate retention stability and
      support for facial and intraoral prostheses used to restore head and neck
      defects. Preliminary studies indicate that in nonirradiated maxillectomy patients
      the success rates are about 75%. In the reconstructed mandible the results appear
      to be more favorable--over 90% for implants placed in free nonvascularized bone
      grafts and over 90% for free revascularized bone grafts. Similar high success
      rates have been observed for most sites used to support facial prostheses.
      Success rates for auricular sites exceed 95% and for floor of nose sites success
      rates exceed 90%. Success rates have been lower (77%) for implants placed in the
      frontal bone for retention of orbital prostheses. Success rates for irradiated
      bone sites have been lower and range from 60.4% in the maxilla to 68.6% in facial
      bone sites. Of greater concern is that most implants placed in irradiated sites
      are beginning to show signs of impending failure.

PMID- 7638505
TI  - Factors affecting choice of initial therapy in oral cancer.
AB  - Choosing the best initial therapy for squamous carcinoma of the oral cavity
      depends on patient factors as well as tumor factors. The patient factors which
      influence the decision include the dental and nutritional status, associated
      diseases, use of alcohol and tobacco, distance from the hospital, and the
      reliability, lifestyle, occupation, and choice of the patient. The important
      tumor factors include size, site, histology, biologic behavior, and type of
      biopsy. With experience and judgment the treatment team (surgeons,
      radiotherapists, dentists, and medical oncologists) can use these patient and
      tumor factors to tailor the therapy to each individual so that not only is the
      cancer optimally treated, but important aspects of function and cosmesis are
      preserved.

PMID- 7638508
TI  - Reconstruction of the pharynx and cervical esophagus.
AB  - The recent twenty years have brought major advances in reconstruction of
      pharyngoesophageal defects. Early dependence on multiple staged procedures
      initially were replaced by colon interposition and gastric pull-up. Subsequent
      elucidation of the musculocutaneous concept has added useful techniques such as
      the sternocleidomastoid and pectoralis major musculocutaneous flaps. Increasing
      experience with microsurgical reconstruction and a larger number of flaps
      available have made free tissue transfer a common and reliable method of
      reconstruction of significant defects. The choice of reconstruction depends to
      greatest degree on the oncologic needs of the situation. If the entire esophagus
      or significant part of the thoracic esophagus is involved by tumor then total
      esophagectomy and gastric pull-up or colon interposition is indicated. For most
      hypopharyngeal and laryngopharyngeal tumors, and a significant number of cervical
      esophageal tumors, segmental resection of the area with the appropriate node
      dissection and replacement with a jejunal free autograft or radial forearm free
      flap gives a high likelihood of success. Thoracic musculocutaneous flaps may be
      useful if proper precautions are observed in the reconstructive technique. This
      article presents the accumulated experience with these techniques and management
      of the subsequent problems.

PMID- 7638509
TI  - Evolution of outcomes in cranial base surgery.
AB  - Cranial base surgery is a young field of head and neck and neuro-oncology. It
      deals with solid tumors at the skull base which were not previously treated with
      surgery. The development of new cranial base approaches incorporating
      intracranial exposure and new reconstructive techniques now enable an "en bloc"
      resection of most of these difficult tumors. In order to analyze the evolution of
      cranial base surgery and its contribution to the treatment of carcinomas and
      sarcomas, we reviewed the results reported in the literature over the past 40
      years. We have designated three periods of time that reflect the advances and
      impact of skull base surgery and have summarized the outcomes of the major
      contributors in each era. The pioneers of the first period (1960s-1970s) achieved
      3- and 5-year survivals of 52 and 49% while attempting resection of tumors
      without intracranial or pytergopalatine extension. In the second period (1970s
      1980s), improved surgical techniques allowed resection of more extensive tumors,
      including intracranial invasion, and 3-year survivals rose to 57-59% with limited
      reports of 5-year survivals in the range of 49%. The third period of cranial base
      surgery (1980s-1990s) brought further refinement of techniques, introduced the
      concept of a coordinated multispecialty approach, and resulted in increased 5
      year survivals to 56-70%.

PMID- 7638510
TI  - Management of cervical lymph nodes in squamous carcinomas of the head and neck.
AB  - Due to the overwhelming prognostic significance of regional metastases, proper
      management of cervical lymph nodes in cases of squamous cell carcinoma of the
      head and neck is essential for an optimal outcome. Better understanding of the
      predictability of incidence and patterns of metastases of these tumors in recent
      years has led us away from the radical neck dissection as the only surgical
      therapeutic or staging procedure done on the neck. Recent studies suggest that
      selective removal of lymph node groups at risk in clinically negative necks, or
      modified neck dissections that save important structures, like the jugular vein,
      XI nerve, and sternocleidomastoid muscle, in clinically positive necks, are
      appropriate in many patients. Careful selection of the type of neck dissection
      and judicious use of postoperative radiation therapy can optimize cure rates as
      well as functional and cosmetic results.

PMID- 7638511
TI  - Changing trends in the management of salivary tumors.
AB  - Fine-needle aspiration biopsy (FNAB) and computed tomography (CT) or magnetic
      resonance imaging (MRI) are useful in the evaluation of salivary gland tumors,
      but they are not essential for treatment planning in every patient. The mainstay
      of therapy is a well-planned and carefully executed surgical procedure which
      adequately excises the tumor. Disease-free survival is very likely in patients
      with early stage malignant tumors. When treatment is delayed until the tumor is
      extensive (Stage 3,4), local recurrence and distant metastases are common and
      survival rates are low. Adjunctive postoperative radiation therapy can enhance
      locoregional control in the latter patients, but does not invariably lead to
      better survival. No consistently effective chemotherapy agents or combinations
      are presently available. Early diagnosis and consistent, high quality treatment
      offer the best hope for improved survival.

PMID- 7638512
TI  - Therapeutic implications of prognostic factors in differentiated carcinoma of the
      thyroid gland.
AB  - Differentiated thyroid carcinoma is a relatively indolent disease. Despite the
      usually favorable prognosis, differentiated thyroid cancer is fatal in some
      patients. In the past, treatment strategies were often based upon incomplete
      knowledge or inaccurate assumptions regarding the significance of the presenting
      characteristics of the tumor and patient. More recently, several large
      retrospective reviews have analyzed various presenting factors and have
      identified those that have prognostic significance and those that do not.
      Significant prognostic factors are age, primary tumor size, histology, grade,
      local tumor extension, and M stage. N stage appears to be a significant factor in
      older patients but not in younger patients. Gender, focality, and a history of
      prior irradiation are not significant prognostic factors. Using this knowledge,
      patients can be grouped into low, intermediate, and high risk groups. Prognostic
      factor and risk group analysis has facilitated the development of more rational
      treatment algorithms. Low risk patients can usually be treated with lobectomy and
      suppression therapy. For high risk patients, total thyroidectomy and adjuvant
      radioiodine is advocated. Treatment for patients in the intermediate risk group
      should be individualized. Prognostic factor and risk group analysis makes a
      selective approach to differentiated thyroid cancer possible. Such an approach
      can spare many patients the morbidity and expense of unnecessarily aggressive
      treatment without compromising outcome.

PMID- 7638513
TI  - Advances in radiotherapy for head and neck cancer.
AB  - Selected advances in radiotherapy for treatment of head and neck cancer are
      reviewed. These include the role of postoperative radiotherapy, planned
      postirradiation neck dissection, altered fractionation, neoadjuvant chemotherapy
      and radiotherapy for laryngeal preservation, three-dimensional conformal
      treatment planning, charged particle irradiation for skull base tumors, and
      stereotactic radiosurgery.

PMID- 7638514
TI  - Chemotherapy advances in head and neck oncology.
AB  - Chemotherapy has an expanding role in the treatment of squamous cell carcinoma of
      the head and neck. Patients with recurrent or metastatic disease that have a good
      performance status should receive combination therapy with cisplatin and 5
      fluorouracil or enter investigational protocols. Neoadjuvant chemotherapy should
      be offered to patients with laryngeal carcinoma as an alternative to surgery.
      Adjuvant chemotherapy should be considered in patients with an increased risk for
      relapse. Combined chemoradiotherapy may improve locoregional control and impact
      on survival. Chemoradiotherapy warrents further investigation through clinical
      trials and should be considered for patients at high risk for relapse. As the
      biology of these tumors becomes better defined, so too will our ability to define
      subsets of patients who may benefit from combined modality treatment.

PMID- 7638515
TI  - Basic science advances in head and neck oncology: the past decade.
AB  - Research advances over the past decade have led to a changing perception of the
      natural history of head and neck cancer. For instance, we now have the capacity
      to quantify and characterize various environmental carcinogens bound to mucosal
      DNA. These DNA adducts provide a quantitative measure of a disease process which
      exists long before clinically defined cancer is recognized. Similarly,
      histopathologically normal mucosa within head and neck cancer patients is
      currently known to express multiple genetic abnormalities including increased
      cellular DNA content, mutations in cell regulatory genes, as well as alterations
      in growth factors and their associated receptors. These subclinical events may,
      likewise, be associated with aberrant cellular proliferation and differentiation
      which provide a target for subsequent therapy. Disease invasion and metastases is
      now seen as a heterogenous process involving a complex of factors intrinsic to
      both the host as well as the cancer. Most significantly, advanced disease is not
      simply defined by its size and location. Rather, the progression of head and neck
      cancer is a dynamic process characterized by increasing genetic instability
      leading to an accumulation of critical mutational events. A biologic basis for
      resistance to treatment is thus being defined. Treatment strategies based on
      these laboratory advances are emerging and involve monoclonal antibody targeting,
      cytokines produced through recombinant molecular technology, and gene therapy.

PMID- 7638516
TI  - Why Brazil should not be a site for AIDS vaccine trials.

PMID- 7638517
TI  - Acquired immunodeficiency syndrome in forensic autopsies.
AB  - From May 1985 to May 1989, 126 necropsies were performed at the Sao Paulo City
      Morgue on cadavers of individuals AIDS victims whose unnatural deaths had
      prompted police investigations. One hundred and nineteen males and 17 females
      were included. Ages were most commonly in the 20-to-30 year range. Fifty four
      deaths occurred in penal institutions, 29 deaths resulted from suicides, 17
      deaths from manslaughter, 17 deaths were considered suspicious, 5 willful murders
      and 4 others also considered suspicious because corpses were found in advanced
      stages of putrefaction. Inmates, except one man who was strangled, died as a
      consequence of the disease. During all autopsies, special attention was paid to
      the high rate of extrapulmonary Mycobacterial infections. Suicides were committed
      in different ways and the majority of the victims were documented to be still in
      the initial stages of the disease. Suspicious deaths and deteriorated corpses
      were the result of negligence of the subject's families. Homicidal deaths
      occurred in subjects in the terminal stages of the disease inside the hospital
      where these subjects were assisted and the immunodeficiency certainly contributed
      to aggravate the injuries leading to death. Attention is drawn to both legal and
      social issues affecting AIDS victims. The authors believe these issues may pose a
      hindrance for efficient control of the AIDS epidemic.

PMID- 7638518
TI  - Behcet's syndrome/AIDS/cerebral toxoplasmosis: an unusual association.
AB  - Few cases of AIDS associated to manifestations suggesting Behcet's syndrome have
      been reported. This case is of a young married woman who presented, during a
      period of 7 years, clinical manifestations consistent with the late diagnosis of
      Behcet's syndrome, when she developed recurrent lymphomonocytic
      meningoencephalitis. At this time, she was found to be infected by HIV-1.
      Immunosuppressive doses of glucocorticoid produced an unsatisfactory response and
      she evolved to death due to CNS toxoplasmosis. The latter diagnosis was presumed
      on the basis of magnetic resonance imaging findings and proved by necropsy after
      her third hospital stay. One of the factors hindering the appropriate diagnosis
      was the low level of CD4 and the CD4/CD8 ratio, sometimes observed in active
      Behcet's syndrome and higher than those observed in patients with this severe
      opportunistic infection. No information about the exact period of time she had
      been infected with HIV-1 is available. So, we do not know whether both diseases
      were overlooked, if the patient, infected by HIV-1, developed an unusual clinical
      feature consistent with Behcet's Behcet's syndrome, and subsequently evolved to
      AIDS.

PMID- 7638519
TI  - The desmoplastic lymph node reaction as a prognostic factor of cancer of the
      tongue and floor of the mouth.
AB  - To determine the prognostic significance of desmoplasia in metastatic lymph nodes
      of squamous cell carcinoma of the oral tongue and floor of mouth, 37 cases of
      this disease were studied. Desmoplasia was present in 59.4% of the cases and
      associated extracapsular spread in 40.5%. The association of desmoplasia with
      large lymph node involvement occurred in 59.4%. These relationships were
      statistically significant (p = 0.002 and 0.0069). The results obtained suggest
      that desmoplasia is a bad prognosis associated factor.

PMID- 7638520
TI  - Complete regression of melanocytic nevi: clues for proper diagnosis.
AB  - A histopathological study of a distinct papule isolated from a patient's neck is
      reported and compared to 80 melanocytic nevi. The histogenesis of this unique
      tumor indicates that it probably represents the residual of a melanocytic nevus
      in which nevi cells have disappeared but fat infiltration and fibrosis of the
      dermis and the typical aspects of other cutaneous elements persisted. The finding
      of focal acantholytic dyskeratosis in multiple foci of the lesion may indicate
      melanocytic cells regression. Lesions with the histopathological appearance of
      melanocytic nevi, even in the absence of nevi cells, may be discovered
      scrutinizing the associated alterations.

PMID- 7638521
TI  - Chronotropic and blood pressure response to oral glucose load in Chagas' disease.
AB  - Cardiac chronotropic and pressor responses after an oral load of glucose were
      assessed in sixteen Chagasic subjects and 28 controls by means of blood pressure
      and pulse rate measurements. Cardiovascular response was correlated with serum
      insulin and glucose levels. The experiment identified a subgroup of Chagasic
      subjects (n = 8) with a hypoinsulinemic behavior presenting less chronotropic and
      pressor responses than controls. This may indicate a lower insulin activity
      and/or an early Autonomic Nervous System dysfunction in this subgroup.

PMID- 7638522
TI  - Acute effects of the Paulinia cupana, "Guarana" on the cognition of normal
      volunteers.
AB  - The authors studied the acute effects of "Guarana", when compared to caffeine and
      placebo, (double blind study) on cognition, anxiety and sleep in 30 normal
      volunteers. Although results were negative it cannot be concluded that "Guarana"
      is harmless. Other studies shall be undertaken, administering "Guarana" on a long
      term basis, as popularly proclaimed.

PMID- 7638523
TI  - Monoclonal antibodies for diagnosis and therapy of squamous cell carcinoma of the
      head and neck.

PMID- 7638524
TI  - Colonic (splenic flexure) necrosis due to thrombosis of the middle colic artery
      following blunt abdominal trauma.
AB  - We report an unusual case of a 28-year-old man who developed a colonic necrosis
      due to thrombosis of the middle colic artery 18 hours following blunt abdominal
      trauma. Although rare, this condition can occur in those patients whom non
      surgical treatment was initially performed.

PMID- 7638525
TI  - [Tempus laborandi et tempus ludendi].

PMID- 7638526
TI  - [Gastric leiomyosarcomas and leiomyoblastomas].
AB  - The authors review the cases with smooth muscle tumors of the stomach (SMTS),
      excluding the leiomyomas, at the Mexico's General Hospital in a period of 5
      years. They found 8 cases in women and 3 in men, with 51.3 years average. The
      average of evolution of symptoms was 5 months, prevailing: anaemia, digestive
      bleeding and abdominal pain. Barium radiology and endoscopy guided to the
      diagnosis. The tumors were located 7 at the fundus, 3 at the body and one at the
      gastric antrum. The size oscillated between 1.5-28 cm., average 8 cm. Endoscopic
      specimens were positive in 2/7 cases and cytologic samples were negative in all
      cases. Eight tumors were leiomyosarcomas (LMS) and 3 were leiomyoblastomas (LMB);
      the histologic criteria in order to differentiate them was based on the number of
      mitosis for 50 fields (50 csf), the size and their hypercellularity. A patient
      died before being operated. Two cases were subjected to emergency surgery, and
      died after that. In the cases treated with elective surgery the authors performed
      subtotal gastrectomy with major omentectomy in 4 and surgical resection of the
      tumor in the remaining 4 patients. The mortality rate for surgery was 27.2%.

PMID- 7638527
TI  - [Delay in hospitalization, diagnosis and surgical intervention in acute
      appendicitis].
AB  - AIMS: To assess if self-medication delays diagnosis and Surgical Treatment in
      acute appendicitis and increases morbidity, mortality and hospital stay as well.
      DESIGN: Retrospective, comparative and observational study. STATISTICS: Chi
      square, exact Fisher test. SUBJECTS AND STUDY GROUPS: 57 patients were subjected
      to appendectomy and were stratified in three groups according to the lapse of
      time between initiation of symptoms and hospitalization: group A less than 24 h
      (n = 20), group B between 24 and 48 h (n = 17), and group C more than 48 h (n =
      20). RESULTS: Groups B and C showed a significant delay for both diagnosis (p <
      0.001) and surgical intervention (p < 0.001) in relation to group A. The
      incidence of acute abdomen presentation showed a positive trend with time of
      hospitalization (p = 0.03). Self-medication increased from group A to C (p <
      0.001). Groups B and C showed a complication rate of 24 and 25%, respectively (p
      > 0.05). Conversely, group A had not complications (p < 0.05). In addition there
      was a 5% mortality due to sepsis in group C. Finally, hospital stay was longer in
      groups B and C (p < 0.001). CONCLUSIONS: Self-medication correlated with delayed
      hospitalization, diagnosis, treatment and complications. Hospital stay was
      consequently longer.

PMID- 7638528
TI  - [Doppler color ultrasonography of the portal vein].

PMID- 7638530
TI  - [Intestine transplantation].

PMID- 7638529
TI  - [Nutrition of patients with liver diseases. (lst of 2 parts)].
AB  - Diet may be modified and can alter the hepatic function or contributes to
      maintain it on excellent state. The objective of this paper was to review the
      recently advances on the clinical aspects of nutrition in chronic liver diseases
      and the underlying rationale for specific nutritional therapies focusing in the
      works in Mexico. Original papers in english and spanish informed on Medline until
      1994 were included. We also review the national literature about nutrition
      aspects on liver diseases.

PMID- 7638531
TI  - [Transjugular intrahepatic portosystemic shunts (TIPS)].

PMID- 7638532
TI  - [Nutrition in patients with liver diseases (second and concluding part)].

PMID- 7638533
TI  - [The effects of early and late weaning on the development of the small intestine
      in the rat: a light-microscopic morphometric study].

PMID- 7638534
TI  - [Helicobacter pylori: gastric ulcer and cancer].

PMID- 7638535
TI  - [The effects of early and late weaning on the development of the small intestine
      in the rat: a light-microscopic morphometric study].
AB  - The small intestine of the rat shows morphologic and enzymatic changes that are
      associated with the weaning and may be alternated by the early weaning, however,
      the morphometric criteria have been disregarded. MATERIAL AND METHODS: In this
      study, the effects of precocious weaning (15 days) and prolonged weaning (32
      days), on the size and number of villi; and crypts of small intestine, were
      analyzed in rats from 16 to 70 days of age. RESULTS: Precocious weaning increased
      the size of villi, depth and number of crypts in the duodenum and jejunum, while
      the number of villi decreased. Pups nursed up to 32 days showed no alterations in
      the analyzed parameters. However, the ileum showed no alterations with the
      precocious weaning or prolonged. CONCLUSIONS: These data support the concept of
      an intrinsic biologic program as control of intestinal development while the
      change of diet seem to have a modifying role in duodenum and jejunum.

PMID- 7638536
TI  - [Neutropenic enteropathy associated with multiple myeloma].
AB  - Neutropenic enteropathy and multiple myeloma. Neutropenic enteropathy (NE) is an
      acute entity with an aggressive clinical behavior. The most common reported
      association of NE is with neutropenic children under chemotherapy for leukemias
      and lymphomas, other less common causes include: neutropenic adults with
      treatment for autoimmune diseases, aplastic anemia, cyclic benign neutropenia or
      solid-neoplasms. There are two cases of NE associated to multiple myeloma (MM).
      There was a 62 year old man with MM diagnosed ten months earlier and under
      chemotherapy. He developed abdominal pain, nausea, vomiting, diarrhea and rectal
      bleeding three days before death. The autopsy study revealed ulcers and
      thickening of the colonic wall in 40% of the entire surface, and in 5% of the
      ileum. The microscopic analysis revealed mucosal and submucosal ischemic
      necrosis, and bacterial invasion without acute inflammatory response. As the two
      previously reported cases, he received vincristine and steroids a few days before
      developing neutropenia. This report shows the clinical and morphologic findings
      of the third case of the association of NE and MM, and the first one illustrated
      in Mexico.

PMID- 7638537
TI  - [Ameboma].

PMID- 7638538
TI  - [Nitric oxide, its importance in gastroenterology and surgery].
AB  - Nitric oxide is an important element that has been found in multiple biological
      systems, including the gastrointestinal tract. The nitric oxide function is
      reviewed, and its possible clinical use is commented.

PMID- 7638539
TI  - An unorthodox approach to diabetes.

PMID- 7638540
TI  - Tailoring care to culture.

PMID- 7638541
TI  - Easing the pain of esophageal surgery.

PMID- 7638542
TI  - Debunking wound care myths.

PMID- 7638543
TI  - Torsades de pointes.

PMID- 7638544
TI  - Diabetes 2000. Acute complications.

PMID- 7638545
TI  - Now hear this!

PMID- 7638546
TI  - What's that GI tube being used for?

PMID- 7638547
TI  - Biofeedback: listen to the body.

PMID- 7638548
TI  - When i.v. practice spells malpractice.

PMID- 7638549
TI  - An alternative for elderly patients in pain.

PMID- 7638550
TI  - We're misusing the intercom.

PMID- 7638551
TI  - Forgetting.

PMID- 7638552
TI  - Circadian variation of blood pressure in patients with chronic renal failure on
      continuous ambulatory peritoneal dialysis.
AB  - The circadian pattern of blood pressure variation was investigated in 10 patients
      with advanced chronic renal failure on continuous ambulatory peritoneal dialysis
      (CAPD) and in an age-matched group of controls without renal disease with similar
      office blood pressure level. Monitoring was done using a non-invasive ambulatory
      blood pressure recorder. Average 24-h blood pressure was significantly higher in
      the group of CAPD patients than in the group of healthy controls, i.e. 141 +/-
      22/82 +/- 8 mmHg (systolic and diastolic blood pressure +/- SD) vs. 126 +/- 18/80
      +/- 7, p < 0.1. This was a result of abnormal 24-h blood pressure profiles among
      CAPD patients. In the group of controls these profiles were in accordance with
      the established normal pattern, whereas nocturnal blood pressure reductions were
      significantly less pronounced in the patient group. The reduction +/- SD in the
      mean arterial blood pressure was 2 +/- 6 mmHg in patients versus 10 +/- 5 mmHg in
      controls, p < 0.01. The mean arterial blood pressure values during daytime (0800
      2000 h) exceeded the night time values (2000-0800 h) in all healthy controls,
      whereas four of 10 patients had higher blood pressure values during the night
      time. In patients with chronic renal failure undergoing CAPD, an otherwise
      unnoticed 24-h hypertension and nocturnal blood pressure elevation can be
      discovered by use of 24-h blood pressure monitoring and this may indicate a need
      of earlier start of antihypertensive treatment in CAPD patients with borderline
      daytime hypertension.

PMID- 7638553
TI  - Long-term lipid-based total parenteral nutrition activates mononuclear cells and
      modulates membrane lipid composition in pigs.
AB  - In previous studies we have found lung granulomas in pigs on long-term soybean
      based total parenteral nutrition (TPN). In the present study we have investigated
      activities and membrane lipids of cells known to participate in a granulomatous
      process. Pigs were given TPN with soybean emulsion for 7 weeks, controls were
      given saline intravenously and consumed a similar caloric load in a standard oral
      diet. Spontaneous nitroblue tetrazolium (NBT) reduction increased 204% in
      peripheral blood mononuclear cells (MNC) from TPN animals compared to controls (p
      < 0.05), and 161% (p = 0.05) in alveolar macrophages. The spontaneous lymphocyte
      mitogen response (LMR) rate in MNC increased 299% (p < 0.05). Endotoxin
      stimulated procoagulant activity in MNC tended to increase in TPN animals. Acid
      phosphatase and lysozyme production in alveolar macrophages were not
      significantly changed. The serum neopterin level at the end of the observation
      was 7.0 nmol l-1 in TPN animals compared to 3.9 nmol l-1 in controls (p < 0.01),
      while interleukin-1 and tumour necrosis factor were not detectable. These
      findings indicated in vivo activation of peripheral blood monocytes, lymphocytes
      and alveolar macrophages in pigs on TPN. The membrane lipid contents of linoleic
      acid (18:2, n-6) increased, while arachidonic acid (20:4, n-6) tended to decrease
      both in MNC and lung tissue. Thus, linoleic acid conversion did not lead to
      accumulation of arachidonate in the cell membranes. Direct effects on monocytes,
      lymphocytes and alveolar macrophages of TPN particles, and altered cell membrane
      function, due to linoleic acid enrichment, are tentative explanations for the
      raised cell responses. Such cell activation may have contributed to the formation
      of granulomas.

PMID- 7638554
TI  - Genetic polymorphism (Arg353-->Gln) in coagulation factor VII gene and factor VII
      levels (coagulant activity, antigen and binding ability to tissue factor) in 101
      healthy Japanese.
AB  - We studied the frequency of the Msp I genotype (Gln353) for factor VII in 101
      young healthy Japanese individuals, and the levels of factor VII-related
      procoagulant activity (FVII:c), antigen (FVII:ag) and binding ability to tissue
      factor (FVII-TF binding). The frequency of the allele coding for the factor VII
      Gln353 was 0.05 among this group. Individuals with genotype M1M1 had an FVII:c of
      103.52 +/- 17.85% (mean +/- SD), FVII:ag of 102.50 +/- 18.42% (mean +/- SD) and
      FVII-TF binding of 101.03 +/- 22.22% (mean +/- SD). Triglyceride levels of
      subjects with the M1M1 genotype were 84.34 +/- 44.97 mg dl-1 (mean +/- SD).
      FVII:c (50%), FVII:ag (45%) and FVII-TF binding (36%) from an individual with the
      M2M2 type was the lowest, with a triglyceride value of 39 mg dl-1. On the other
      hand, individuals with the genotype M1M2 had an FVII:c of 75.57 +/- 9.61% (mean
      +/- SD), FVII:ag of 72.43 +/- 8.54% (mean +/- SD) and FVII-TF binding of 68.14 +/
      14.91% (mean +/- SD). FVII:c, FVII:ag and FVII-TF binding in individuals with
      the M1M2 and M2M2 genotypes were significantly lower than those in individuals
      with the M1M1 genotype.

PMID- 7638555
TI  - Identification of the apo B-3500 mutation in the Norwegian population.
AB  - Familial defective apolipoprotein B-100 (FDB) is caused by a mutation in codon
      3500 of the apo B gene. It is inherited in a co-dominant fashion and is
      characterized by hypercholesterolaemia. Thus, FDB has similar features to
      familial hypercholesterolaemia (FH). In order to investigate whether some of the
      Norwegian subjects diagnosed as having FH actually have FDB, we have screened 208
      Norwegian FH heterozygotes for the apo B-3500 mutation. One of the subjects
      possessed the mutation which was on a haplotype compatible with the mutation
      bearing haplotype found in other populations. Although, hypercholesterolaemia
      segregated with haplotypes both at the apolipoprotein B and low density
      lipoprotein (LDL) receptor loci in the proband's family, LDL receptor analysis
      revealed that the proband was not doubly heterozygous for FDB and FH.

PMID- 7638556
TI  - Intrapancreatic turnover of recombinant human pancreatic secretory trypsin
      inhibitor in experimental porcine pancreatitis.
AB  - Experimental porcine pancreatitis was induced by the injection of taurocholate
      into the pancreatic duct. Recombinant human pancreatic secretory trypsin
      inhibitor (25 mg) was administered to each animal in one of three different ways:
      into the pancreatic duct (n = 5), into the abdominal cavity adjacent to the
      pancreas (n = 2) or intravenously (n = 2). The intrapancreatic turnover was
      assessed during 6 h using a microdialysis technique. The intraglandular
      concentration, measured by enzyme-linked immunosorbent assay, was highest after
      injection of rhPSTI into the pancreatic duct and substantially lower after
      intravenous and intraperitoneal administration. The intrapancreatic half-life of
      the inhibitor after intraductal administration was considerably longer (3-6
      times) in pigs with pancreatitis than has previously been found in the normal
      gland. These facts argue in favour of the intraductal administration route in
      future trials of antiprotease treatment in acute pancreatitis.

PMID- 7638557
TI  - Caffeine metabolism in patients with chronic liver disease.
AB  - An oral load of 200 mg (1030 mumol) caffeine (CA) was given to 13 patients with
      chronic liver diseases and to 11 healthy controls. The metabolism of CA was
      determined by following plasma concentrations and urinary excretion of CA and its
      metabolites. In addition, [2-14C]-caffeine was given orally to six patients to
      confirm the excretion through the different pathways. CA and its 14 main
      metabolites were separated and quantified by high performance liquid
      chromatography and capillary electrophoresis. Median (interquartile range) half
      lives of CA were 19 (6.3-32) h in the patients and 3.8 (3.4-4.7) h in the
      controls. The wide range in the patients indicated varying degrees of liver
      dysfunction. Only 3 (2-4)% of administered CA was excreted unmetabolized in urine
      in the controls and the main degradation was through the paraxanthine (PX)
      pathway 82 (75-83)%. The combined theobromine (TB) and theophylline (TP) pathways
      (TB + TP) accounted for 15 (13-21)% of CA metabolism. Although the excretion of
      unmetabolized CA in the patients 6 (3-8)%, was similar to that in the controls,
      the metabolism through the PX pathway, 62 (44-65)%, decreased (p < 0.01 vs.
      controls), whereas the metabolism through the TB + TP pathways increased to 33
      (30-47)%, p < 0.01. In controls, N3-, N7- and N1-demethylations were observed in
      86 (83-89)%, 66 (62-70)% and 13 (9-18)%, respectively, of excreted metabolites.
      In patients the N3-demethylations, 71 (66-77)%, and N7-demethylations, 54 (48
      59)%, decreased (p < 0.01 vs. controls), whereas N1-demethylation increased 30
      (21-46)%, p < 0.01. The major C8-oxidation reaction, the oxidation of 1
      methylxanthine, increased in patients (p < 0.01). We conclude that the slowed
      metabolism of CA in chronic liver disease is due to reduced N3- and N7
      demethylations affecting biotransformation through the PX pathway.

PMID- 7638558
TI  - Health-based reference intervals for ALAT, ASAT and GT in serum, measured
      according to the recommendations of the European Committee for Clinical
      Laboratory Standards (ECCLS).
AB  - The reference intervals for the activities of L-alanine aminotransferase (EC
      2.6.1.2, ALAT), L-aspartate aminotransferase (EC 2.6.1.1, ASAT) and gamma
      glutamyltransferase (EC 2.3.2.2, GT) in serum were determined according to the
      recommendations of the European Committee for Clinical Laboratory Standards
      (ECCLS). Serum specimens from 954 subjects were analysed for ALAT and ASAT and
      from 794 subjects for GT. The subjects, aged 27-67 years, were participants in
      general health surveys. The reference population was formed by excluding subjects
      with any disease, or on any medication, affecting the liver, and also those
      consuming excessive amounts of alcohol. The 95% inner reference intervals for
      ALAT and ASAT were 9-50 (n = 189) and 15-36 U l-1 (n = 192) in men and 8-38 (n =
      270) and 13-33 U l-1 (n = 270) in women. For GT the reference interval was 11-58
      in men (n = 165) and 8-42 U l-1 in women (n = 220). Serum GT levels correlated
      clearly with alcohol consumption. Serum ALAT and ASAT were only slightly
      associated with alcohol consumption at levels less than 280 g per week in men and
      190 g per week in women. There were modest positive associations between the
      three enzyme levels and body mass index. None of the enzymes correlated
      significantly with age.

PMID- 7638559
TI  - Effects of prolonged tourniquet ischaemia and short-term venous stasis on plasma
      endothelin-1 levels in man.
AB  - In vitro studies have indicated increased endothelial release of endothelin
      during tissue and cellular hypoxia. Therefore, we studied the effect of
      tourniquet ischaemia and venous stasis on plasma endothelin-1 (ET-1) levels in
      humans in vivo. The effect of hypoxia on plasma ET-1 levels in 16 patients
      subjected to an orthopaedic operation and six healthy volunteers was studied by
      (a) tourniquet ischaemia, in which a limb is totally emptied of blood and kept
      ischaemic by means of a pneumatic tourniquet, and (b) venous stasis in an upper
      arm. The mean (SEM) basal plasma ET-1 concentration in the patients subjected to
      tourniquet ischaemia of a lower limb was 4.1 (1.0) pg ml-1. No significant change
      in plasma ET-1 levels during or after tourniquet ischaemia was found. The mean
      (SEM) plasma ET-1 concentration in six healthy subjects prior to venous occlusion
      in the right upper arm was 3.3 (0.7) and 2.7 (0.3) pg ml-1 in the right and left
      arm, respectively. A significant increase in plasma ET-1 concentration after 20
      min was observed in the arm subjected to venous stasis, but not in the other,
      control, arm. Mean arterial blood pressure did not change significantly. Local
      tissue hypoxia may not be an important stimulus for ET-1 release in humans in
      vivo, whereas short-term venous occlusion in an upper arm leads to local release
      of ET-1 by an as yet unknown mechanism.

PMID- 7638560
TI  - Bone mass in non-insulin-dependent diabetes mellitus.
AB  - In view of the contradictory results of earlier reports regarding bone mass in
      patients with non-insulin-dependent diabetes, we measured bone mass using dual X
      ray absorptiometry and ultrasound measurements of the right calcaneus in 36 type
      2 diabetic subjects, i.e. 21 men and 15 postmenopausal women aged 40-65 years,
      and compared their bone mass to a sex- and age-matched control group. We also
      measured several metabolic parameters in the diabetic population and studied the
      relationship between these metabolic parameters and the bone parameters using
      correlation analysis. We found a tendency to higher bone mass in the diabetic
      subjects compared to the normal controls. In the Type 2 diabetic postmenopausal
      women, fat mass and lean body mass correlated positively with total body bone
      mineral density (BMD) (r = 0.53 and 0.68), and with total body bone mineral
      content (BMC) (r = 0.58 and 0.77). Insulin sensitivity (GDR/I) correlated
      negatively with total body BMC and BMD (r = -0.68 and -0.61). Serum insulin
      correlated positively with the same bone parameters. When controlling for fat
      mass or lean body mass using a multiple regression analysis, the correlation
      between insulin sensitivity and BMD became non-significant. This suggests that
      body mass is a more important determinant of BMD than hyperinsulinaemia or
      insulin resistance in diabetic women. Among the diabetic men there was a
      significant positive correlation between lean body mass and BMC (r = 0.66),
      between serum oestrone and BMD (r = 0.49) and between serum insulin and femoral
      neck BMD (r = 0.53).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7638561
TI  - Frequency of common cystic fibrosis gene mutations in chronic bronchitis
      patients.
AB  - It has been suggested that the delta F508 deletion, the most common mutation in
      the cystic fibrosis (CF) gene, might be linked to chronic bronchial
      hypersecretion. We investigated whether such an association could be found in
      chronic bronchitis, since chronic bronchial hypersecretion is an important and
      specific element of chronic bronchitis. We screened 100 patients hospitalized for
      chronic bronchitis with six of the most frequently occurring CF gene mutations:
      delta F508, R553X, G542X, G551D, N1303K, and 621-1G-->T. Only one patient
      affected by chronic bronchitis and diffuse bronchiectasis was heterozygous for
      the deletion delta F508; no other mutations were found. This is not significantly
      different from the expected frequency of CF carriers in northern Europe, which is
      1 in 25. Thus, no association between the most commonly occurring cystic fibrosis
      genes and chronic bronchitis is likely to exist and routine screening of patients
      without further signs of cystic fibrosis would seem to be of no benefit in
      northern Europe.

PMID- 7638562
TI  - The protein concentration of blood coagulation factor VII can be measured equally
      well in plasma and serum.
AB  - In the Northwick Park Heart Study, the coagulant activity of factor VII (FVII:C)
      has been identified as a risk marker of ischaemic heart disease. In the fasting
      state, the protein concentration of FVII (FVII:Ag) might be an even better risk
      marker, because of the low coefficient of variation of the antigen assay. Today,
      most analyses are performed in plasma samples, as it is unknown whether FVII, to
      some extent, is consumed during coagulation. In the present study, we have
      investigated, whether FVII:Ag can be measured equally well in plasma and serum.
      FVII:Ag was measured in 88 plasma and serum samples. Results were compared by
      means of linear regression, where y = 0.984 x +0.770, r = 0.96. No systematic
      variation existed between FVII:Ag in plasma and serum. The mean difference in
      FVII:Ag between plasma and serum was -1.17 (SD 11.92) arbitrary units, compared
      with a mean difference of 0.18 (SD 8.31) arbitrary units between duplicate
      measurements of the same plasma dilution. Our findings indicate that there is a
      good agreement between FVII:Ag in plasma and serum.

PMID- 7638563
TI  - The best therapy for Helicobacter pylori infection: should efficacy or side
      effect profile determine our choice?

PMID- 7638564
TI  - Patterns of gastric emptying in dysmotility-like dyspepsia.
AB  - BACKGROUND: As the gastric emptying time delay of patients with functional
      dyspepsia is not correlated with the severity of dyspepsia complaints, we
      investigated the pattern of intragastric distribution of a meal with an
      ultrasonographic method in different groups of dyspeptic patients. METHODS: The
      final gastric emptying time and the postprandial variations of the cross
      sectional area of the gastric antrum were measured ultrasonographically, and
      dyspeptic symptoms were scored in 41 patients with dysmotility-like dyspepsia, of
      whom 31 did not have digestive or systemic diseases known to affect gut motility
      (group A) and 10 had scleroderma involving the upper gut (group B). Twelve normal
      subjects were examined as a control group. RESULTS: The final emptying times of
      groups A and B did not differ significantly but were both significantly longer
      than that of controls, whereas the antral area at 60 min showed a significantly
      greater increase in patients of group A than in group B. The symptom score showed
      significantly more severe dyspepsia in group A than in group B. CONCLUSIONS: The
      fact that the postprandial antral distention was more marked in the dyspeptic
      patients with more severe symptoms suggests that this motor pattern could play a
      more important role in the genesis of dyspeptic symptoms than the delay in
      gastric emptying time, which was similar in the two groups.

PMID- 7638565
TI  - Dyspepsia--how noisy are gallstones? A meta-analysis of epidemiologic studies of
      biliary pain, dyspeptic symptoms, and food intolerance.
AB  - BACKGROUND: In contrast to earlier beliefs, it is nowadays assumed that no
      relation exists between dyspeptic symptoms and the presence of gallstones.
      Although many studies indeed failed to show a relation, each has been too small
      to exclude it. The aim of this meta-analysis is to systematically review
      epidemiologic studies and to synthesize the data. METHODS: Twenty-one controlled
      studies on the association between gallstones and dyspeptic symptoms were
      analyzed after critical appraisal with regard to selection bias, blinding,
      confounding, and data presentation. Most of them had reasonable validity.
      Inconsistencies between results of the studies could not be explained by
      differences in study design or validity. There was a slight indication of
      publication bias. RESULTS: Upper abdominal pain was consistently associated with
      gallstones (pooled odds ratios, about 2.0), with no preference for the right
      side. The findings on biliary pain were inconsistent. The results exclude with
      reasonable certainty an association between gallstones and 'classical' dyspeptic
      symptoms such as flatulence, heartburn, and acid regurgitation, bloating, and
      belching. An exception was nausea and vomiting (odds ratio, 1.4). Unspecified
      food intolerance was related to gallstones, but fat intolerance was not.
      CONCLUSIONS: We conclude that it is not sensible to call dyspeptic symptoms
      'gallstone dyspepsia', since component symptoms do not show a consistent relation
      with gallstones, and their diagnostic meaning over and above abdominal pain has
      not been evaluated.

PMID- 7638566
TI  - Chronic systemic treatment with epidermal growth factor induces hypergastrinaemia
      in Goettingen minipigs.
AB  - BACKGROUND: Epidermal growth factor (EGF) is an inhibitor of gastric acid
      secretion. The impact of chronic systemic treatment with EGF on intragastric pH
      and serum gastrin concentrations has not been investigated previously. METHODS:
      Goettingen minipigs were treated with human recombinant EGF (hEGF) or placebo for
      4 weeks. Once a week the acidity and protein concentration of gastric juice were
      determined, and serum gastrin concentrations measured. After 4 weeks, tissue
      specimens were obtained from the gastric antrum and immunostained for gastrin-
      and somatostatin-producing G- and D-cells. Furthermore, the development of
      antibodies against hEGF was evaluated. RESULTS AND CONCLUSION: Subcutaneously
      administered hEGF, 30 micrograms/kg/day for 4 weeks, included a fourfold increase
      in basal serum gastrin concentration, increased the number of antral G-cells, and
      decreased the density of antral D-cells. The acidity of gastric fluid was
      reduced, and the protein concentration increased. All animals developed low
      titred antibodies towards hEGF. The antibodies did not influence the extent to
      which the individual animal responded to the EGF treatment.

PMID- 7638567
TI  - Chronic gastritis in patients with gastric ulcer; a 10-year follow-up.
AB  - BACKGROUND: The course of gastric ulcer disease and its relations to certain
      indicators of inflammation and Helicobacter pylori in the gastric mucosa were
      examined in a 10-year follow-up. METHODS: Thirty-three patients with gastric
      ulcer were examined endoscopically with biopsies in 1981-82 and invited for re
      examination in 1991-92. Twenty-one of them were able to comply with the
      invitation. A gastroscopy with biopsies was performed on each of these, and the
      results were compared with those of age- and sex-matched control patients with
      non-ulcer H. pylori-positive gastritis. RESULTS: All the patients were H. pylori
      positive at the first examination and had a persistent infection at the second
      examination, if they had not undergone a gastric resection. Thirteen patients had
      a non-operated stomach at the second examination. The grades of gastritis and
      intestinal metaplasia in the antrum at the second examination were significantly
      higher in the ulcer patients than in the controls (p = 0.009 and p = 0.04,
      respectively). Eosinophilic granulocytes in both the antral and the corpus mucosa
      had decreased significantly in the controls (p = 0.002 and p = 0.04,
      respectively) but not in the ulcer patients. CONCLUSIONS: The results suggest
      that the course of ulcer-associated H. pylori-positive gastritis is different
      from that of non-ulcer-associated H. pylori-positive gastritis and that abnormal
      eosinophilic infiltration persists in patients with gastric ulcer.

PMID- 7638568
TI  - Avirulent, urease-deficient Helicobacter pylori colonizes gastric epithelial
      explants ex vivo.
AB  - BACKGROUND: Urease-negative Helicobacter pylori generated by insertional
      mutagenesis fails to colonize gnotobiotic piglets, and this effect is largely
      independent of gastric pH. The purpose of this study was to determine whether
      urease-negative H. pylori colonized gastric explants ex vivo. METHODS: Gastric
      mucosal explants derived from neonatal germ-free piglets were inoculated with
      either wild-type H. pylori or one of two mutants derived by insertional
      mutagenesis. RESULTS: All three bacterial strains colonized explants. The level
      of colonization increased over the duration of the experiment, reaching 10(8)
      10(9) cfu/g gastric mucosa by 72 h after inoculation. Morphologic evidence of
      colonization was similar to that observed in gnotobiotic piglets. CONCLUSIONS:
      Colonization of explants was not affected by lack of urease. These results
      contrast with previous findings showing that urease activity is essential for
      colonization of piglets by H. pylori. Thus, urease-dependent colonization is
      dependent on an intact gastric microenvironment.

PMID- 7638569
TI  - Nonsteroidal anti-inflammatory drugs and upper gastrointestinal bleeding,
      identifying high-risk groups by excess risk estimates.
AB  - BACKGROUND: The relationship between use of nonsteroidal anti-inflammatory drugs
      (NSAID) and severe upper gastrointestinal bleeding (UGB) has been established
      beyond reasonable doubt. The literature on risk factors has almost exclusively
      focused on comparisons of relative risks in subgroups of patients: men versus
      women, old versus young and so forth. However, from a pragmatic, clinical
      viewpoint, only the excess risk provides a meaningful, robust measure of the
      magnitude of risk factors. The purpose of the study was to determine the excess
      risks in subgroups of patients and to characterize the utilization pattern of
      NSAIDs. METHODS: A registry-based cohort study was conducted in a prescription
      and diagnosis registry in Odense, which covered a population of 207,000 persons
      for a period of 19 months. RESULTS: In total, 183 (113 men and 70 women) UGB
      patients were identified, of whom 37 were current users of NSAIDs. The
      standardized incidence rate of UGB was 46 per 100,000 person-years for nonexposed
      and 253 per 100,000 person-years for exposed person-time, yielding an excess risk
      of 207 per 100,000 person-years (confidence interval (CI), 132-319) and a
      standardized incidence ratio (SIR) of 5.5 (CI, 3.9-7.9). Men had higher excess
      risk than women (277 versus 150 per 100,000 person-years). The SIR decreased with
      increasing duration of exposure. The excess risk was particularly high in persons
      aged 75 years or more (1258 per 100,000 person-years) and in patients with a
      history of peptic ulcer (879 per 100,000 person-years), being about 10- and 5
      fold higher than in the complementary groups. NSAID utilization was remarkably
      sporadic. We found 31,503 users and a median purchase of 20 defined daily doses.
      Short-term use was highly prevalent in all age groups. Women, the elderly, and
      persons with a history of ulcer had a higher prevalence of NSAID use than others.
      CONCLUSIONS: A history of peptic ulcer is associated with adverse outcome of
      NSAID therapy and should be regarded as a relative contraindication. A similarly
      strong effect of high age was shown. Male sex and short-term use are minor risk
      factors. The incidence of NSAID-related UGB can probably be reduced without
      affecting the overall utilization of NSAIDs.

PMID- 7638570
TI  - Indomethacin-induced lesion modifies contractile activity in rat small
      intestines.
AB  - BACKGROUND: Indomethacin induces intestinal lesions. The change in contractility
      of segments with lesions was studied. METHODS: Motility was recorded in segments
      with lesions isolated from the rat small intestine 24 h after a subcutaneous
      injection of indomethacin (20 mg/kg). RESULTS: Concentration-contraction curves
      for acetylcholine shifted leftward independently of the degree of severity of
      lesions, but the curves for carbachol and 5-hydroxytryptamine did not.
      Contractions produced by intramural nerve stimulation were enhanced in segments
      with no visible damage but decreased with progression of lesions. Neostigmine
      augmented them in normal rats but not in indomethacin-treated rats. The
      peristaltic activity was enhanced in segments with no visible lesions.
      CONCLUSIONS: The results suggest that treatment of the rat with indomethacin
      enhances contractility of the small intestine owing to diminution of
      acetylcholinesterase activity independently of the degree of lesions and reduces
      it owing to decreased responsiveness of enteric neurons with the progression of
      lesions.

PMID- 7638571
TI  - Effect of mild malnutrition on disaccharidase activity and glucose uptake in
      intestinal brush border vesicles of growing monkeys.
AB  - BACKGROUND: The effect of severe malnutrition has been reported by some workers,
      but there is a paucity of information on milder forms even though 85% of pre
      school children show evidence of mild to moderate malnutrition in India. METHODS:
      Mild to moderate protein energy malnutrition was induced in 12 monkeys, and 12
      were kept as controls. After a 30-40% reduction in body weight as compared with
      their controls, the animals were killed, and brush border membrane vesicles were
      prepared from three small parts of the small intestine. Purified vesicles were
      used for the assay of lactase, sucrase, maltase and glucose uptake in vitro.
      RESULTS: The activity of lactase, sucrase, and maltase, and uptake of (U-14C)-D
      glucose was decreased in all three parts of small intestine, and the lactose
      tolerance test result was also abnormal in the protein energy-malnourished group.
      On nutritional rehabilitation, the disaccharidase activities recovered
      completely. CONCLUSION: This study indicates that even mild to moderate
      malnutrition decreases the digestion and absorption of carbohydrates throughout
      the small intestine, and it should not be ignored during the developing stage.

PMID- 7638572
TI  - Expression of tumour necrosis factor-alpha, interleukin-6, and interleukin-2 mRNA
      in the jejunum of patients with coeliac disease.
AB  - BACKGROUND: A T-cell-mediated immune response may be responsible for the
      enteropathy seen in coeliac disease (CD), but it is unclear whether this is
      initiated in the epithelium or the lamina propria. We studied the site and number
      of cells expressing mRNA encoding the cytokines interleukin-2 (IL-2), IL-6, and
      tumour necrosis factor-alpha in jejunal biopsy specimens from patients with
      untreated or treated CD and normal controls. METHODS: Tissue sections were
      hybridized with 35S-labelled DNA oligonucleotide probes specific for each
      cytokine RNA sequence. Positive cells were counted in the lamina propria and
      epithelial compartments. RESULTS: For each cytokine significantly greater numbers
      of positive cells were found in the lamina propria of untreated CD patients. Few
      positive cells were detected in the epithelium of all three groups. CONCLUSIONS:
      This study shows that the immune response to gliadin appears to occur in the
      lamina propria and supports cell-mediated immunity in the pathogenesis of coeliac
      disease.

PMID- 7638573
TI  - Importance of vasoactive intestinal peptide and somatostatin for fluid losses in
      small-bowel obstruction.
AB  - BACKGROUND: Previous observations have shown vasoactive intestinal peptide (VIP)
      to be an important secretagogue in the gut, whereas somatostatin has been
      reported to inhibit VIP release and fluid secretion. METHODS: The possible role
      of VIP as mediator of the inflammation and fluid losses in obstructive ileus was
      investigated in vivo and in a chronic rat model with thread ligation of the
      jejunum. Extravasated Evans blue (Eb)-stained albumin was quantified by
      spectrophotometry. Net fluid secretion was measured by a gravimetric technique.
      VIP antiserum was used to inhibit the effects of endogenous VIP. A somatostatin
      analogue, octreotide, was used to inhibit the release of VIP. RESULTS: Results
      showed a pronounced plasma Eb-albumin extravasation in the wall of the obstructed
      gut, which was significantly inhibited by VIP antiserum (p < 0.05) or octreotide
      (p < 0.01). Obstruction of the jejunum resulted in net fluid secretion that was
      significantly reduced by administration of octreotide (p < 0.01) or VIP antiserum
      (p < 0.05). Net fluid secretion in control animals remained constant.
      CONCLUSIONS: These findings suggest that VIP is an important mediator of the
      pathophysiology in mechanical intestinal obstruction and that somatostatin may be
      involved in the endogenous control of fluid losses.

PMID- 7638574
TI  - Treatment of internal rectal intussusception in patients with chronic
      constipation.
AB  - BACKGROUND: The significance of internal rectal intussusception (rectal
      invagination) in chronic constipation dominated by symptoms of obstructed
      defecation is not fully clarified. METHODS: Seventeen consecutive patients with
      chronic constipation and a history of obstructed defecation with internal rectal
      intussusception demonstrated by defecography were treated by perineal rectopexy.
      RESULTS: Of 15 patients followed up for more than 2 years defecography showed
      total disappearance of the intussusception in 12. Five of these claimed
      substantial improvement (42%; 17-72%). Three of four patients with concomitant
      anal incontinence became fully or partly continent after the rectopexy.
      CONCLUSION: In some patients with chronic constipation, dominated by symptoms of
      obstructed defecation, rectal invagination may be an aggravating factor. The
      study indicates that rectal invagination does not seem to be the cause but rather
      a consequence of the obstructed defecation. In selected patients, including those
      with concomitant faecal incontinence, surgical treatment of the intussusception
      by a minor procedure may be indicated.

PMID- 7638575
TI  - Importance of endoscopically visualized recurrent ileitis and small-bowel
      resection for symptoms in Crohn's disease.
AB  - BACKGROUND: The relationship between the endoscopic appearance of the ileal
      mucosa in Crohn's disease and the symptoms has not been studied. Although surgery
      is important, morbidity caused by intestinal resections and its relation to
      recurrent inflammation have been poorly evaluated. METHODS: The relationship of
      symptoms to various ileoscopic signs of inflammation and previous intestinal
      resection was prospectively studied in 75 postresection Crohn patients. RESULTS:
      Multivariate analysis showed that a combination of anastomotic width, pus, and
      length of previous small-bowel resection best explained a symptom score (r =
      0.53, p < 0.001). Of 40 patients with the anastomosis strictured to less than 15
      mm, only 9 had moderate to severe symptoms. Patients with a stricture diameter <
      10 mm differed significantly in symptom score (p < 0.05) from those with wider
      anastomoses. CONCLUSIONS: The study indicated that intestinal resection was as
      important for symptoms as endoscopically viewed recurrent ileal inflammation. The
      diameter at which an intestinal stricture produces symptoms is less than
      previously argued, and the association of small-bowel resection with symptoms
      underlines the advisability of minimal surgery.

PMID- 7638576
TI  - Experimental foreign-body infection in the biliary tract in rats.
AB  - BACKGROUND: Biomaterials used for biliary drainage may potentially result in
      biomaterial-associated infections. METHODS: Foreign-body infection in the biliary
      tract was investigated in rats. Rubber drain pieces were implanted in the biliary
      tract in rats for 1-4 weeks, followed by challenges with 10(2) to 10(4) colony
      forming units (cfu) Escherichia coli injected into the common bile duct. The rate
      of infection was calculated, the bacterial growth in the biliary tract was
      observed over 72 h after challenges, and the opsonic activity in bile and in sera
      was assessed. RESULTS: In the group with drain material, inocula as small as
      10(2) cfu produced persisting infection in the common bile duct in 90% of
      animals, whereas the same number of E. coli infected only 30% of rats in the
      control and sham implantation groups (p < 0.01, chi-square test). Complement
      mediated opsonic activity in bile of animals with implanted drain pieces
      gradually decreased with time, whereas opsonic activity in sera from the same
      animals remained unchanged. CONCLUSIONS: Implants in the biliary tract impair
      local host defense, resulting in an increased susceptibility to microbial
      infection.

PMID- 7638577
TI  - Percutaneous cholecystolithotomy: risks, benefits, and long-term outcome.
AB  - BACKGROUND: For symptomatic patients with gallbladder stones and a patent cystic
      duct who wish to retain their 'functioning' gallbladders, percutaneous
      cholecystolithotomy (PCCL) offers an alternative to open or laparoscopic
      cholecystectomy. However, there are few data on the risks and benefits of this
      approach or on the long-term outcome. METHODS AND RESULTS: In 21 patients with
      symptomatic calcified gallstones, PCCL was successful (gallstone clearance) in 17
      (81%). Four to 62 (median, 35) months after clearance 9 of the 17 remained
      symptom-free and stone-free, whereas 4 developed biliary sludge at 7, 30, 32, and
      35 months, 2 of whom subsequently developed gallstones. In four other patients
      gallstones recurred without evidence of preceding biliary sludge at 9, 16, 19,
      and 27 months, corresponding to an actuarial gallstone recurrence rate at 36
      months of 53.4 +/- SEM 15.1%, and a combined stone/sludge recurrence rate of 63.4
      +/- 13.5%. CONCLUSIONS: PCCL is moderately effective but, because of the
      frequency of complications and sludge/stone recurrence, is likely to have only a
      limited residual role in the era of laparoscopic cholecystectomy.

PMID- 7638578
TI  - Endoscopic sclerotherapy in a rat model of esophageal varices.
AB  - BACKGROUND: Partial ligation of the portal vein has been shown to induce not only
      prehepatic portal hypertension but also esophageal varices in the rat. We
      developed an esophageal endoscopic system for endoscopic sclerotherapy of
      esophageal varices in rats. In the present study the efficacy of three sclerosing
      agents, 1% polidocanol, 5% ethanolamine oleate, and 99.5% ethanol, was compared,
      using this model. METHODS: Sclerosing agents were injected paravariceally in 42
      rats with partial portal vein ligation. Their efficacy was compared
      endoscopically and histologically. RESULTS: Ethanol induced the most severe
      ulcers and subsequent stricture formation. The damage induced by 1% polidocanol
      was mild and healed quickly, whereas 5% ethanolamine oleate induced moderate
      damage. The varices disappeared because of fibrosis that developed after
      ulceration. CONCLUSIONS: The results were consistent with the known properties of
      these three agents, suggesting that the esophageal endoscopic system for
      sclerotherapy in rats provides a useful method for experimental studies of
      sclerotherapy.

PMID- 7638580
TI  - House puts its stamp on the budget.

PMID- 7638581
TI  - Gene therapy. NIH picks three gene vector centers.

PMID- 7638579
TI  - Equity in biomedical research.

PMID- 7638582
TI  - In the fruit fly, cell death genes may come in pairs.

PMID- 7638583
TI  - Remains in Spain now reign as oldest Europeans.

PMID- 7638584
TI  - Malaria. How the parasite disguises itself.

PMID- 7638585
TI  - Women's Health Research.

PMID- 7638586
TI  - Women's health research blossoms.

PMID- 7638587
TI  - Zeroing in on how hormones affect the immune system.

PMID- 7638588
TI  - Attacking the causes of "silent" infertility.

PMID- 7638589
TI  - Women: absent term in the AIDS research equation.

PMID- 7638590
TI  - New push to reduce maternal mortality in poor countries.

PMID- 7638591
TI  - Global approaches to the promotion of women's health.

PMID- 7638592
TI  - International perspectives on women's reproductive health.

PMID- 7638593
TI  - Women in clinical trials: an FDA perspective.

PMID- 7638594
TI  - The inclusion of women in clinical trials.

PMID- 7638595
TI  - Patients in research: not just subjects, but partners.

PMID- 7638596
TI  - Depression in women: implications for health care research.
AB  - Epidemiologic data from around the world demonstrate that major depression is
      approximately twice as common in women than men and that its first onset peaks
      during the childbearing years. Progress has been made in understanding the
      epidemiology of depression and in developing effective treatments. Much remains
      to be learned about the basic pathogenesis of depression and the specific
      treatment needs of depressed women and their offspring, especially during the
      reproductive years.

PMID- 7638598
TI  - Lower Pleistocene hominids and artifacts from Atapuerca-TD6 (Spain)
AB  - Human remains dating to more than 780,000 years ago are associated with a rich
      faunal and lithic assemblage in the Pleistocene cave site of Gran Dolina (TD),
      Sierra de Atapuerca, Burgos, Spain. The micromammal species represent the late
      Biharian (Mimomys savini zone), and the lithic objects represent pre-Acheulean
      technology (Mode 1) and comes from the TD6 level below the Matuyama-Brunhes
      boundary. The Gran Dolina hominid fossils cannot be comfortably accommodated in
      any of the defined Homo species. They could be considered a primitive form of
      Homo heidelbergensis, but a new species might be named in the future if the
      sample is enlarged. The new human fossil evidence demonstrates that Western
      Europe was settled at least since the late early Pleistocene.

PMID- 7638597
TI  - Regulatory subunit of protein kinase A: structure of deletion mutant with cAMP
      binding domains.
AB  - In the molecular scheme of living organisms, adenosine 3',5'-monophosphate
      (cyclic AMP or cAMP) has been a universal second messenger. In eukaryotic cells,
      the primary receptors for cAMP are the regulatory subunits of cAMP-dependent
      protein kinase. The crystal structure of a 1-91 deletion mutant of the type I
      alpha regulatory subunit was refined to 2.8 A resolution. Each of the two tandem
      cAMP binding domains provides an extensive network of hydrogen bonds that buries
      the cyclic phosphate and the ribose between two beta strands that are linked by a
      short alpha helix. Each adenine base stacks against an aromatic ring that lies
      outside the beta barrel. This structure provides a molecular basis for
      understanding how cAMP binds cooperatively to its receptor protein, thus
      mediating activation of the kinase.

PMID- 7638599
TI  - Paleomagnetic age for hominid fossils at Atapuerca archaeological site, Spain.
AB  - A paleomagnetic investigation at the Gran Dolina site excavation (Atapuerca,
      Spain) shows that the sediments containing the recently discovered human
      occupation were deposited more than 780,000 years ago, near the time of the
      Matuyama-Brunhes boundary. Forty-one oriented samples were obtained from 22 sites
      along an 18-meter section of the Gran Dolina karst filling. The lower 16 sites
      displayed reversed-polarity magnetizations whereas the upper six sites were
      normal. The reversal spans the hominid finds at stratigraphic level TD6 (the
      Aurora stratum), and these hominid fossils are therefore the oldest in southern
      Europe.

PMID- 7638600
TI  - Functional significance of symmetrical versus asymmetrical GroEL-GroES chaperonin
      complexes.
AB  - The Escherichia coli chaperonin GroEL and its regulator GroES are thought to
      mediate adenosine triphosphate-dependent protein folding as an asymmetrical
      complex, with substrate protein bound within the GroEL cylinder. In contrast, a
      symmetrical complex formed between one GroEL and two GroES oligomers, with
      substrate protein binding to the outer surface of GroEL, was recently proposed to
      be the functional chaperonin unit. Electron microscopic and biochemical analyses
      have now shown that unphysiologically high magnesium concentrations and increased
      pH are required to assemble symmetrical complexes, the formation of which
      precludes the association of unfolded polypeptide. Thus, the functional
      significance of GroEL:(GroES)2 particles remains to be demonstrated.

PMID- 7638601
TI  - Asymmetrical interaction of GroEL and GroES in the ATPase cycle of assisted
      protein folding.
AB  - The chaperonins GroEL and GroES of Escherichia coli facilitate protein folding in
      an adenosine triphosphate (ATP)-dependent reaction cycle. The kinetic parameters
      for the formation and dissociation of GroEL-GroES complexes were analyzed by
      surface plasmon resonance. Association of GroES and subsequent ATP hydrolysis in
      the interacting GroEL toroid resulted in the formation of a stable
      GroEL:ADP:GroES complex. The complex dissociated as a result of ATP hydrolysis in
      the opposite GroEL toroid, without formation of a symmetrical GroEL:(GroES)2
      intermediate. Dissociation was accelerated by the addition of unfolded
      polypeptide. Thus, the functional chaperonin unit is an asymmetrical GroEL:GroES
      complex, and substrate protein plays an active role in modulating the chaperonin
      reaction cycle.

PMID- 7638602
TI  - Structure of the Arabidopsis RPM1 gene enabling dual specificity disease
      resistance.
AB  - Plants can recognize pathogens through the action of disease resistance (R)
      genes, which confer resistance to pathogens expressing unique corresponding
      avirulence (avr) genes. The molecular basis of this gene-for-gene specificity is
      unknown. The Arabidopsis thaliana RPM1 gene enables dual specificity to pathogens
      expressing either of two unrelated Pseudomonas syringae avr genes. Despite this
      function, RPM1 encodes a protein sharing molecular features with recently
      described single-specificity R genes. Surprisingly, RPM1 is lacking from
      naturally occurring, disease-susceptible Arabidopsis accessions.

PMID- 7638603
TI  - Ultrasound-mediated transdermal protein delivery.
AB  - Transdermal drug delivery offers a potential method of drug administration.
      However, its application has been limited to a few low molecular weight compounds
      because of the extremely low permeability of human skin. Low-frequency ultrasound
      was shown to increase the permeability of human skin to many drugs, including
      high molecular weight proteins, by several orders of magnitude, thus making
      transdermal administration of these molecules potentially feasible. It was
      possible to deliver and control therapeutic doses of proteins such as insulin,
      interferon gamma, and erythropoeitin across human skin. Low-frequency ultrasound
      is thus a potential noninvasive substitute for traditional methods of drug
      delivery, such as injections.

PMID- 7638604
TI  - Parietal contributions to visual feature binding: evidence from a patient with
      bilateral lesions.
AB  - Neurophysiologists have documented the existence of multiple cortical areas
      responsive to different visual features. This modular organization has sparked
      theoretical interest in how the "binding problem" is solved. Recent data from a
      neurological patient (R.M.) with bilateral parietal-occipital lesions
      demonstrates that the binding problem is not just a hypothetical construct; it
      can be a practical problem, as rare as the selective inability to perceive motion
      or color. R.M. miscombines colors and shapes even under free viewing conditions
      and is unable to judge either relative or absolute visual locations. The evidence
      suggests that a single explanation--an inadequate spatial representation--can
      account for R.M.'s spatial judgment and feature-binding deficits.

PMID- 7638605
TI  - Behavioral effects and gene delivery in a rat model of Parkinson's disease.

PMID- 7638606
TI  - Degrees of freedom.

PMID- 7638607
TI  - Malathion and alternatives.

PMID- 7638608
TI  - Mutations not sufficient for carcinogenesis?

PMID- 7638609
TI  - Klausner follows own advice at NCI.

PMID- 7638610
TI  - Missing Alzheimer's gene found.

PMID- 7638611
TI  - Human origins. New hominid crowds the field.

PMID- 7638612
TI  - Biochemistry. New angle for classic tale of respiratory protein and oxygen.

PMID- 7638613
TI  - Ancient DNA. The trials and tribulations of cracking the prehistoric code.

PMID- 7638614
TI  - The mechanism of biphasic GABA responses.

PMID- 7638615
TI  - Resonance light scattering: a new technique for studying chromophore aggregation.
AB  - Light scattering experiments are usually performed at wavelengths away from
      absorption bands, but for species that aggregate, enhancements in light
      scattering of several orders of magnitude can be observed at wavelengths
      characteristic of these species. Resonance light scattering is shown to be a
      sensitive and selective method for studying electronically coupled chromophore
      arrays. The approach is illustrated with several examples drawn from porphyrin
      and chlorin chemistry. The physical principles underlying resonance light
      scattering are discussed, and the advantages and limitations of the technique are
      reviewed.

PMID- 7638616
TI  - Control of electron transfer between the L- and M-sides of photosynthetic
      reaction centers.
AB  - An aspartic acid residue has been introduced near ring V of the L-side accessory
      bacteriochlorophyll (BCHlL) or the photosynthetic reaction center in a
      rhodobacter capsulatus mutant in which a His also replaces Leu 212 on the M
      polypeptide. The initial stage of charge separation in the G(M201)D/L(M212)H
      double mutant yields approximately 70 percent electron transfer to the L-side
      cofactors, approximately 15 percent rapid deactivation to the ground state, and
      approximately 15 percent electron transfer to the so-called inactive M-side
      bacteriopheophytin (BPhM). It is suggested here that the Asp introduced at M201
      modulates the reduction potential of BCHlL, thereby changing the energetics of
      charge separation. The results demonstrate that an individual amino acid residue
      can, through its influence on the free energies of the charge-separated states,
      effectively dictate the balance between the forward electron transfer reactions
      on the L-side of the RC, the charge-recombination processes, and electron
      transfer to the M-side chromophores.

PMID- 7638617
TI  - Crystal structure of a conserved protease that binds DNA: the bleomycin
      hydrolase, Gal6.
AB  - Bleomycin hydrolase is a cysteine protease that hydrolyzes the anticancer drug
      bleomycin. The homolog in yeast, Gal6, has recently been identified and found to
      bind DNA and to act as a repressor in the Gal4 regulatory system. The crystal
      structure of Gal6 at 2.2 A resolution reveals a hexameric structure with a
      prominent central channel. The papain-like active sites are situated within the
      central channel, in a manner resembling the organization of active sites in the
      proteasome. The Gal6 channel is lined with 60 lysine residues from the six
      subunits, suggesting a role in DNA binding. The carboxyl-terminal arm of Gal6
      extends into the active site cleft and may serve a regulatory function. Rather
      than each residing in distinct, separable domains, the protease and DNA-binding
      activities appear structurally intertwined in the hexamer, implying a coupling of
      these two activities.

PMID- 7638618
TI  - Protein reaction kinetics in a room-temperature glass.
AB  - Protein reaction kinetics in aqueous solution at room temperature are often
      simplified by the thermal averaging of conformational substates. These substates
      exhibit widely varying reaction rates that are usually exposed by trapping in a
      glass at low temperature. Here, it is shown that the solvent viscosity, rather
      than the low temperature, is primarily responsible for the trapping. This was
      demonstrated by placement of myoglobin in a glass at room temperature and
      subsequent observation of inhomogeneous reaction kinetics. The high solvent
      viscosity slowed the rate of crossing the energy barriers that separated the
      substates and also suppressed any change in the average protein conformation
      after ligand dissociation.

PMID- 7638619
TI  - Binding of CO to myoglobin from a heme pocket docking site to form nearly linear
      Fe-C-O.
AB  - The relative orientations of carbon monoxide (CO) bound to and photodissociated
      from myoglobin in solution have been determined with time-resolved infrared
      polarization spectroscopy. The bound CO is oriented < or = 7 degrees from the
      heme normal, corresponding to nearly linear FE-C-O. Upon dissociation from the
      Fe, CO becomes trapped in a docking site that orientationally constrains it to
      lie approximately in the plane of the heme. Because the bound and "docked" CO are
      oriented in nearly orthogonal directions CO binding from the docking site is
      suppressed. These solutions results help to establish how myoglobin discriminates
      against CO, a controversial issue dominated by the misconception that Fe-C-O is
      bent.

PMID- 7638620
TI  - Association of flavin adenine dinucleotide with the Arabidopsis blue light
      receptor CRY1.
AB  - The arabidopsis thaliana HY4 gene encodes CRY1, a 75-kilodalton flavoprotein
      mediating blue light-dependent regulation of seedling development. CRY1 is
      demonstrated here to noncovalently bind stoichiometric amounts of flavin adenine
      dinucleotide (FAD). The redox properties of FAD bound by CRY1 include an
      unexpected stability of the neutral radical flavosemiquinone (FADH.). The
      absorption properties of this flavosemiquinone provide a likely explanation for
      the additional sensitivity exhibited by CRY1-mediated responses in the green
      region of the visible spectrum. Despite the sequence homology to microbial DNA
      photolyases, CRY1 was found to have no detectable photolyase activity.

PMID- 7638621
TI  - A familial Alzheimer's disease locus on chromosome 1.
AB  - The Volga German kindreds are a group of seven related families with autosomal
      dominant early-onset Alzheimer's disease (AD). Linkage to known AD-related loci
      on chromosomes 21 and 14 has been excluded. Significant evidence for linkage to
      AD in these families was obtained with D1S479 and there was also positive
      evidence for linkage with other markers in the region. A 112-base pair allele of
      D1S479 co-segregated with the disease in five of seven families, which is
      consistent with a common genetic founder. This study demonstrates the presence of
      an AD locus on chromosome 1q31-42.

PMID- 7638622
TI  - Candidate gene for the chromosome 1 familial Alzheimer's disease locus.
AB  - A candidate gene for the chromosome 1 Alzheimer's disease (AD) locus was
      identified (STM2). The predicted amino acid sequence for STM2 is homologous to
      that of the recently cloned chromosome 14 AD gene (S182). A point mutation in
      STM2, resulting in the substitution of an isoleucine for an asparagine (N141l),
      was identified in affected people from Volga German AD kindreds. This N141l
      mutation occurs at an amino acid residue that is conserved in human S182 and in
      the mouse S182 homolog. The presence of missense mutations in AD subjects in two
      highly similar genes strongly supports the hypothesis that mutations in both are
      pathogenic.

PMID- 7638623
TI  - Ionic mechanisms of neuronal excitation by inhibitory GABAA receptors.
AB  - Gamma-aminobutyric acid A (GABAA) receptors are the principal mediators of
      synaptic inhibition, and yet when intensely activated, dendritic GABAA receptors
      excite rather than inhibit neurons. The membrane depolarization mediated by GABAA
      receptors is a result of the differential, activity-dependent collapse of the
      opposing concentration gradients of chloride and bicarbonate, the anions that
      permeate the GABAA ionophore. Because this depolarization diminishes the voltage
      dependent block of the N-methyl-D-aspartate (NMDA) receptor by magnesium, the
      activity-dependent depolarization mediated by GABA is sufficient to account for
      frequency modulation of synaptic NMDA receptor activation. Anionic gradient
      shifts may represent a mechanism whereby the rate and coherence of synaptic
      activity determine whether dendritic GABAA receptor activation is excitatory or
      inhibitory.

PMID- 7638624
TI  - Recurrent excitation in neocortical circuits.
AB  - The majority of synapses in the mammalian cortex originate from cortical neurons.
      Indeed, the largest input to cortical cells comes from neighboring excitatory
      cells. However, most models of cortical development and processing do not reflect
      the anatomy and physiology of feedback excitation and are restricted to serial
      feedforward excitation. This report describes how populations of neurons in cat
      visual cortex can use excitatory feedback, characterized as an effective "network
      conductance", to amplify their feedforward input signals and demonstrates how
      neuronal discharge can be kept proportional to stimulus strength despite strong,
      recurrent connections that threaten to cause runaway excitation. These principles
      are incorporated into models of cortical direction and orientation selectivity
      that emphasize the basic design principles of cortical architectures.

PMID- 7638625
TI  - Object-centered direction selectivity in the macaque supplementary eye field.
AB  - Object-centered spatial awareness--awareness of the location, relative to an
      object, of its parts--plays an important role in many aspects of perception,
      imagination, and action. One possible basis for this capability is the existence
      in the brain of neurons with sensory receptive fields or motor action fields that
      are defined relative to an object-centered frame. In experiments described here,
      neuronal activity was monitored in the supplementary eye field of macaque monkeys
      making eye movements to the right or left end of a horizontal bar. Neurons were
      found to fire differentially as a function of the end of the bar to which an eye
      movement was made. This is direct evidence for the existence of neurons sensitive
      to the object-centered direction of movements.

PMID- 7638626
TI  - Nonspecific DNA bending and the specificity of protein-DNA interactions.

PMID- 7638627
TI  - Breast cancer: are imaging studies cost effective following breast cancer and
      adjuvant therapy?

PMID- 7638628
TI  - Introduction: myeloproliferative disorders.

PMID- 7638630
TI  - Agnogenic myeloid metaplasia.

PMID- 7638629
TI  - Polycythemia rubra vera.
AB  - PV represents a clonal disorder characterized by excessive erythropoiesis
      accompanied by low serum EPO levels. Two populations of erythroid progenitors
      have been identified in the BM of patients with PV. One population responds
      normally to EPO and the other, the malignant clone, is exquisitely sensitive to
      EPO. The latter phenomenon is regarded as the most readily accepted explanation
      for the pathophysiology of this disease, although other mechanisms have been
      proposed. Thrombohemorrhagiccomplications, which usually correlate with the
      hematocrit level, are the most important because of their frequency and severity.
      Preventing such complications represents one of the most important therapeutic
      goals. Diagnostic criteria have been established enabling an accurate diagnosis
      of PV, in which the majority of patients live an excess of 10 years. Some will
      develop a falling hematocrit secondary to PPMM, also termed the spent phase.
      Patients may also develop acute leukemia, which is increased in incidence if
      myelosuppressive therapy is used, compared with phlebotomies alone. The initial
      treatment is phlebotomy to an hematocrit of 45% or less. The studies of the PVSG
      have shown that chlorambucil produces excessive mortality from malignancy, and
      32P and phlebotomy are associated with superior survivals which are equivalent.
      Because of the substantial risk of thrombotic complications, elderly patients,
      ie, those older than 70 years, should be treated initially with phlebotomy and
      myelosuppressive therapy, usually 32P. Hydroxyurea appears less leukemogenic than
      32P or alkylating agents; however, recent reports have questioned this. IFN is a
      promising new agent which may become a standard form of therapy in the future.

PMID- 7638631
TI  - Primary thrombocythemia.

PMID- 7638632
TI  - Chromosome abnormalities in the myeloproliferative disorders.

PMID- 7638633
TI  - Hematopathologic findings in the myeloproliferative disorders.
AB  - In the preceding paragraphs, the features that define the various members of the
      CMPD have been reviewed. These features are summarized in Table 4. Knowledge of
      these guidelines will aid the clinician and pathologist in arriving at a proper
      classification; however, in most cases, it is the occasional patient whose
      clinical, laboratory, and morphologic findings lie across the different
      categories that unifies these CMPDs, and that provides the challenge which makes
      them interesting.

PMID- 7638634
TI  - Chronic myelogenous leukemia as a model of cancer development.

PMID- 7638635
TI  - Clinical manifestations of chronic granulocytic leukemia.
AB  - CGL is a highly specific disease that is defined by strict hematologic parameters
      that include a pathognomonic differential leukocyte count. Usually CGL is
      accompanied by the presence, in bone marrow cells, of the Ph chromosome, the
      first chromosomal anomaly to be regularly associated with a human neoplastic
      disease. CGL is predominantly a disease of the productive middle years of life,
      which maximizes its adverse impact on family life and family economics. The
      disease is of worldwide distribution and there is a slight male preponderance.
      The disease is characterized by an initial chronic phase when it behaves as a
      differentiated neoplasm and responds very well to simple, nonintensive therapy.
      After a variable interval, CGL undergoes metamorphosis to a refractory phase that
      responds poorly or sometimes not at all to therapy, even when this is intensive.
      At the stage of metamorphosis a great variety of clinical and hematologic
      pictures occur, and CGL may mimic a myeloproliferative disease, a myelodysplasia,
      a subacute leukemia, AML, or ALL. The old concept of an abrupt, explosive
      transition from the chronic phase to a so-called blastic crisis is incorrect:
      this rarely occurs and in most patients who are carefully followed, CGL is
      observed to undergo two or more stepwise evolutions, eg, from chronic phase to an
      accelerated myeloproliferative phase to a phase that resembles AML. Many patients
      with CGL conform to an established pattern of clinical features. There is a
      history of insidious symptoms of anemia and of splenomegaly. The physical signs
      are those of pallor and marked splenomegaly, while the hematologic findings are
      of moderate anemia, moderate thrombocytosis, and a marked granulocytic
      leukocytosis with a specific differential count. The radiologic findings are
      typically normal. Diagnostic difficulty seldom arises with this classic
      presentation. The patient who is detected at an early stage of CGL may lack the
      history, physical signs, and fully developed hematologic picture of CGL. Before
      the availability of cytogenetic studies, the diagnosis could only be established
      with confidence by observing the patient until the typical features of the
      disease emerged. Also considered are the less frequent but important atypical
      presentations of CGL. The symptoms and complaints, findings on examination,
      complications and hematologic findings may depart from the typical case in a
      bewildering variety of ways, so that the diagnosis may be difficult, indeed, CGL
      is generally not the initial diagnosis that is made. When the patient with CGL
      has received treatment, it is usual for he or she to become asymptomatic, with no
      abnormal physical signs.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7638636
TI  - Treatment of chronic myelogenous leukemia.
AB  - Allogeneic BMT and IFN-A-based therapy have undoubtedly changed the natural
      history of CML. Despite these advances, many patients still die from their
      disease. Most patients do not qualify for an allogeneic BMT either because of age
      or lack of an appropriate donor, and only a fraction of patients achieve a
      complete cytogenetic remission with IFN-A-based therapy. The timing of BMT and
      treatment sequences of IFN-A and BMT have been discussed. Prior treatment with
      IFN-A does not seem to affect transplant outcome; however, delaying
      transplantation has been reported to impact adversely on transplant results.
      Until controlled trials are performed, the issue of optimal timing of allogeneic
      BMT will remain controversial. The use of alternative donors may extend the
      option of allogeneic BMT to younger patients; however, for older patients this
      therapeutic modality still has an unacceptably high incidence of morbidity and
      mortality with current BMT regimens and other alternative treatments are needed.
      Investigational strategies searching for ways of improving the proportion of
      patients achieving complete cytogenetic remissions with IFN-A therapy need to be
      actively explored. These include new agents (eg, HHT) or new modalities such as
      intensive chemotherapy with autologous stem cell transplantation with in vitro
      purging. Investigators in the field must decide whether to continue randomized
      trials of IFN-A versus conventional chemotherapy, or to explore strategies that
      may enhance the effect of IFN-A-based therapy. Only when the durable cytogenetic
      response rates with IFN-A combinations increase to 40% or 50% will it be of value
      to proceed to phase III trials. Further understanding in the basic biology of CML
      and the effect of IFN-A in this disease will also provide clues to improving
      therapy with the goal of obtaining long-term disease control and cures in the
      majority of patients with the least burden of therapy.

PMID- 7638637
TI  - Bone marrow transplantation for chronic myelogenous leukemia.
AB  - Based on our understanding of CML, we recommend that patients age 65 or less with
      newly diagnosed CML should be evaluated to determine the stage of their disease
      and should be human lymphocyte antigen-typed along with their siblings. Patients
      age 55 years and younger who have matched or single antigen mismatched siblings
      should be advised to undergo BMT as soon as possible and patients up to age 65
      should be considered for BMT early in their disease course if in good health.
      Patients age 55 years or younger without appropriately matched family member
      donors should have a search for an unrelated donor initiated and should be
      offered BMT if an appropriate donor is found. Patients for whom no donor is found
      and older patients without family matches can be considered for entry onto
      clinical trials evaluating autologous BMT or other experimental approaches.

PMID- 7638638
TI  - Innovative approaches to breast cancer treatment: the role of paclitaxel.
      Introduction.

PMID- 7638639
TI  - Interim results of a phase I/II study of biweekly paclitaxel and cisplatin in
      patients with metastatic breast cancer.
AB  - Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) administered in a
      3-hour infusion exhibits both a rapid decline to, and recovery from, the
      hematologic nadir. This suggests that a biweekly administration schedule of this
      agent either alone or in combination with agents that have limited hematologic
      toxicity may be possible. The objective of this study was to determine the
      tolerability and activity of biweekly administered paclitaxel in combination with
      cisplatin in patients with metastatic breast cancer. Patients with metastatic
      breast cancer who may have received up to one prior chemotherapy regimen in the
      adjuvant setting were eligible. Paclitaxel was administered intravenously by a 3
      hour infusion followed by intravenous cisplatin every 2 weeks in the ambulatory
      setting. Twenty-nine patients have been entered in the study, of whom 27 had
      received prior adjuvant chemotherapy. Dose-limiting toxicity for the phase I
      study proved to be failure to recover the neutrophil count to more than 750
      cells/microL by day 15; the maximum tolerated dose was therefore paclitaxel 90
      mg/m2 and cisplatin 60 mg/m2 every 2 weeks. Nonhematologic toxicities were mild
      and included fatigue, arthralgias, peripheral neuropathy, and nausea and
      vomiting. At the present analysis, 234 cycles of treatment have been given. Among
      27 patients evaluable for response (four of whom are still receiving therapy),
      three have had complete remissions and 18 partial responses, for an interim
      overall response rate of 78%. In summary, weekly paclitaxel and cisplatin is a
      safe and active combination in the treatment of metastatic breast cancer. Final
      determination of toxicity and activity will be published at the conclusion of
      this study.

PMID- 7638640
TI  - Phase II randomized study of paclitaxel versus mitomycin in advanced breast
      cancer.
AB  - Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has been shown to
      be an effective agent in the treatment of metastatic breast carcinoma. This
      multicenter randomized study compared paclitaxel 175 mg/m2 given as a 3-hour
      infusion every 3 weeks with mitomycin 12 mg/m2 given as an intravenous infusion
      every 6 weeks. Eighty-one patients have been randomized, and preliminary results
      of a planned analysis of the first 36 evaluable patients per arm are reported.
      Pretreatment characteristics were well balanced between the two groups. All
      patients previously have received chemotherapy for metastatic disease, and half
      had both adjuvant therapy and chemotherapy for metastatic disease. All but one
      patient previously had received anthracyclines. Of the first 81 randomized
      patients, 72 were evaluable for response and toxicity (four never treated, five
      concomitant hormonotherapy). Partial responses were seen in 17% of patients in
      the paclitaxel arm and 6% in the mitomycin arm (P = .14). Crossover to paclitaxel
      therapy following progression on mitomycin achieved an objective response rate of
      24% (five of 21 patients). Responses to paclitaxel therapy lasted for a median
      duration of 9.1 months (range, 6.2 to 12+ months). Median time to progression was
      significantly longer in the paclitaxel arm (3.5 months v 1.6 months; P = .026).
      The quality-of-life-adjusted analysis confirmed the advantage of paclitaxel
      therapy, even when the delay of disease progression was adjusted for important
      adverse events. Adverse events, most importantly neutropenia and neuropathy, were
      more frequently observed in the paclitaxel arm. However, patients remained on
      paclitaxel therapy for many more courses than did those treated in the mitomycin
      arm. In conclusion, paclitaxel 175 mg/m2 given as a 3-hour intravenous infusion
      has been demonstrated to be an active agent in the treatment of chemotherapy
      refractory advanced breast cancer, even after therapy with mitomycin has failed.

PMID- 7638641
TI  - The effect of a national control of diarrheal diseases program on mortality: the
      case of Egypt.
AB  - The National Control of Diarrheal Diseases Project (NCDDP) of Egypt began in
      1981, became fully operational nation-wide by 1984, and concluded in 1991. The
      project was designed as a campaign to lower mortality from diarrheal disease in
      children under five by at least 25% within five years. The principal strategy
      employed was to improve case-management of diarrhea through rehydration and
      better feeding: through assured production and distribution of oral rehydration
      salts, education of families through mass media and health workers through
      training programs, and creation of rehydration corners throughout the established
      primary health care and hospital network. A detailed plan for evaluation and
      research was designed at the start of the project. By its own terms, the NCDDP
      appears to have succeeded in improving case management; by several local and
      national mortality surveys, overall infant and childhood mortality fell by at
      least one-third with the majority proportion in diarrheal deaths. The declines
      coincided with the peak of NCDDP activities and results in improved case
      management. The detailed analyses of this monograph seek to demonstrate that: (a)
      the mortality decline and the diarrheal mortality decline in particular were
      actual events; (b) that case-management improved with plausible sufficiency to
      account for most of the diarrheal mortality reduction; and (c) that changes in
      other proximate determinants to lowered mortality, such as host resistance or
      diarrheal incidence, do not plausibly account for the magnitude of the reductions
      seen. Data are also presented on general socio-economic changes in the decade of
      the Project. We conclude that improvements in primary care delivery and the use
      of mass media would have been facilitating factors to NCDDP efforts, while the
      overall deterioration of economic status would have tended to reduce the
      benefits. The monograph details the strengths and weaknesses of the available
      data, and also makes recommendations for sustained efforts in the control of
      diarrheal diseases.

PMID- 7638642
TI  - The social course of epilepsy: chronic illness as social experience in interior
      China.
AB  - Findings are reported from a collaborative research project on the experience of
      epilepsy and treatment among patients and family members in Shanxi and Ningxia
      Provinces in China. Family, marriage, financial and moral consequences of the
      social experience of epilepsy support the conceptualization of chronic illness as
      possessing a social course. Beyond traditional concern with stigma, application
      of concepts of delegitimation, sociosomatic processes, coping as resistance,
      contestation in the evaluation of efficacy and compliance, and the cultural
      ontology of suffering illustrate other ways that social theory is useful in
      research on chronic illness and disability.

PMID- 7638643
TI  - Paradise lost: an introduction to the geography of water pollution in Puerto
      Rico.
AB  - Rapid industrialization has transformed the agricultural economy of Puerto Rico,
      creating employment opportunities and raising standards of living. Success,
      however, is marred by widespread pollution that outstrips the infrastructural
      capacity necessary for the preservation of environmental quality and of human
      health. The result today is a landfill crisis, a heritage of toxic dumps, and an
      advancing tide of pollution. Rivers and reservoirs are nearly ubiquitously
      affected and groundwaters, long thought to be naturally protected, show evidence
      of increasing contamination. Limestone aquifers are at particular risk. Public
      awareness and inter-sectoral political leadership are urgently needed to reverse
      the trend towards environmental deterioration.

PMID- 7638644
TI  - A longitudinal examination of the Cherniss model of psychological burnout.
AB  - This study is a longitudinal examination of a process model of psychological
      burnout proposed by Cherniss [1; Professional Burnout in Human Service
      Organizations (1980)]. In this model, work setting characteristics and individual
      difference variables have both direct effects on burnout and indirect effects on
      burnout through levels of experienced stress. Data were collected at two points
      in time separated by one year using questionnaires. Respondents were 362 school
      based educators. Considerable support for the Cherniss model was found using path
      analysis.

PMID- 7638646
TI  - Child survival in big cities: the disadvantages of migrants.
AB  - Data from 15 Demographic and Health Surveys are used to examine whether rural
      urban migrants in developing countries experience higher child mortality after
      settling in towns and cities than do lifelong urban residents, and if so, what
      individual or household characteristics account for this. Findings indicate that
      children of female migrants from the countryside generally have much poorer
      survival chances than other urban children. This survival disadvantage is more
      pronounced in big cities than in smaller urban areas, among migrants who have
      lived in the city for many years than among recent migrants, and in urban Latin
      America than in urban North Africa and sub-Saharan Africa. Within big cities,
      higher child mortality among migrant women is clearly related to their
      concentration in low-quality housing, and in part to fertility patterns at early
      ages of children and mother's educational attainment at later ages. Excess child
      mortality among urban migrants may also result from factors associated with the
      migration process, that are outlined in this study but not included in the
      analysis. Evidence of moderately high levels of residential segregation of
      migrant women in big cities suggests that opportunities exist for urban health
      programs to direct interventions to this disadvantaged segment of city
      populations.

PMID- 7638645
TI  - Dealing with uncertainty: will science solve the problems of resource allocation
      in the U.K. NHS?
AB  - In spite of the huge efforts which internationally address the development and
      assessment of health technologies, the majority of health care interventions have
      not been formally evaluated for their effectiveness and their likely impact upon
      health status is largely unknown. This has led to a situation where it is unclear
      on what basis a health care system might be judged, or for that matter on what
      basis decisions on the specification of individual services might be made. It has
      frequently been argued that the only way to build an adequate understanding of
      the effectiveness of different interventions is through systematically locating
      and synthesising the available evidence from research, and such systematic
      overviews are increasingly available in many areas. However, such overviews
      produce few clear conclusions, and even when the results of systematic overviews
      show unequivocal benefits for patients, implementing the findings of such reviews
      remains problematic. Research evidence provides useful information on marginal
      benefits for patients, though areas where the absolute benefit is high appear to
      be very rare. The most common finding appears to be uncertainty. Interpreting
      research evidence is complex, and even very clear findings may prove hard to
      operationalise. Good quality research will help, but will not solve, the problems
      of resource allocation in the NHS or in other health systems.

PMID- 7638647
TI  - The validity of using health state indexes in measuring the consequences of
      traffic injury for public health.
AB  - This paper describes an assessment of the validity of using health state indexes
      as a means of describing the consequences of traffic injury for public health.
      Three issues are discussed: (1) Can questionnaire data be used as input for
      estimating health state values by means of health state indexes? (2) Can the
      validity of describing the consequences of traffic injury by means of different
      health state indexes (QALY-indexes) be assessed? (3) Can estimated health state
      values be used directly as a basis for decision making? It is concluded that
      questionnaire data can be used as input of health state value estimation. Four
      health state indexes are compared: The Quality of Well Being Scale, The McMaster
      Health Classification System, The Rosser and Kind Index and the EuroQol
      Instrument (transformed version). It is concluded that an assessment of the
      validity of these indexes is possible, and that the EuroQol Instrument appears to
      be the most valid of the four indexes that are compared. None of the four indexes
      give values that are consistent with public policy objectives, but objectives
      were not set with the benefit of knowing the relative utility loss associated
      with injuries at different levels of severity.

PMID- 7638648
TI  - The influence of socioeconomic status on change in health status after
      hospitalization.
AB  - We reviewed patients' hospital records and surveyed patients after hospital
      discharge to determine whether the experience of being hospitalized
      differentially affected the health status of persons with different socioeconomic
      backgrounds (as measured by income level and education level) and to determine
      whether the association between socioeconomic status (SES) and change in health
      status varied depending upon the reason for hospital admission. We studied
      patients admitted to six university-affiliated teaching hospitals in
      Massachusetts and California for chest pain (N = 797) and surgery (N = 1165). We
      compared the health status scores of patients for a variety of outcomes: basic
      activities of daily living, instrumental activities of daily living, social
      activities, mental well-being, work performance and housework performance. Lower
      SES patients entered the hospital with worse health status than higher-SES
      patients. Change in health status, statistically adjusted for case-mix, varied by
      reason for admission. Patients with chest pain generally reported either no
      improvement or a decline in functioning with the amount of decline equivalent for
      low- and high-SES patients. Surgical patients reported improvement in functioning
      following hospitalization. For several measures, lower-income surgical patients
      reported greater improvement than did higher-income patients, but still did not
      reach the same level of health status as higher-income patients.

PMID- 7638649
TI  - The effects of caring on health: a community-based longitudinal study.
AB  - This paper begins with a critical review of studies which have examined the
      effects of caring on health. Most are shown to suffer from defects in sampling
      and design, so that the evidence for detrimental effects is suggestive rather
      than conclusive. The substantive part of the paper then utilizes data on a cohort
      of 55-year-olds to compare the health of carers with the health of non-carers and
      to examine changes in caring and health over a 3-year period. The comparison
      yields no systematic evidence of the deleterious effects of caring on health;
      indeed, if there is a tendency in the accumulated data, it is in the opposite
      direction i.e. that carers report better health and functioning than non-carers.
      It is suggested that part of the explanation relates to selection and self
      selection and the longitudinal data reveals high volatility in caring status,
      even over a short time period. The paper goes on to examine sub-groups of carers
      considered to be at greater risk. There is no evidence that their health is
      compromised but the authors acknowledge weaknesses in the data and argue for a
      specially designed study. The paper concludes with a discussion of the findings
      and their implications for research, policy and practice.

PMID- 7638650
TI  - Menstrual cycle symptom reporting in three British ethnic groups.
AB  - Three different British ethnic groups were targeted to assess the influence of
      learned or culturally prescribed symptom reporting behaviour across different
      phases of the menstrual cycle. Forty-eight Afro-Caribbean, 73 Caucasian and 32
      Oriental subjects completed a Positive/Negative Affectivity scale, a
      Retrospective assessment of premenstrual symptoms and daily symptom reports for
      35 days. The results showed a significantly elevated level of symptomatology
      premenstrually and menstrually in the Caucasian group compared to both others.
      Analysis of subscales suggested elevated symptom reporting occurred for the
      psychological mood, body symptoms and pain, but not for the mental performance
      and social behaviour subscales. Intermenstrual reports of symptoms and Negative
      Affectivity did not differ between groups. A response bias or underlying trait is
      therefore unlikely to account for the selective reporting observed. It is
      suggested that the question of learning variables playing an important role in
      the reporting of symptoms at different phases of the menstrual cycle may be
      reopened.

PMID- 7638651
TI  - Health, just world beliefs and coping style preferences in patients of
      complementary and orthodox medicine.
AB  - This study was designed to compare health and Just World Beliefs, coping style
      preferences and the mental health of a group of patients that utilize
      complementary medicine (CM), a group that exclusively use orthodox medicine (OM)
      and a mixed group who use both. Each participant filled out a questionnaire
      consisting of four sections: a measure of health beliefs which attributed certain
      factors to the state of their current health and to their capacity to become
      healthier in the future; a measure of the extent of their Belief in a Just World;
      a measure of coping style preference when faced with a threatening situation; and
      a measure of mental health. The results, co-varying out demographic factors,
      showed differences between the group yielded significant differences on the
      beliefs about future health, with the CM group scoring higher than the OM group.
      There were no differences in coping styles, Just World Beliefs or mental health
      between the three groups. The results were discussed in relation to explanations
      for differences in illness behaviour, specifically the reasons for choosing
      complementary therapies against orthodox therapies for the treatment of illness.

PMID- 7638652
TI  - The Patient's Charter: a survey of hospital out-patients views of their rights
      and ability to exercise them.

PMID- 7638653
TI  - Traumatic instability of the lumbar spine. A dynamic in vitro study of flexion
      distraction injury.
AB  - STUDY DESIGN: This in vitro study determined the effect on the lumbar spine of a
      dynamic flexion-distraction loading simulating a lap seatbelt injury. The
      proportion by which the forces and the moments contributed to the injury of the
      lumbar spinal segment in such a situation was analyzed. The remaining stability
      of the injured lumbar motion segment was determined together with the threshold
      for lumbar spine instability in such an injury. OBJECTIVES: Based on the
      experimental results in this study, radiographic guidelines for instability
      criteria in lumbar and thoracolumbar dislocations in the sagittal plane without
      concomitant compression fracture of the middle column were proposed. SUMMARY OF
      BACKGROUND DATA: A number of check-lists and guidelines were suggested for the
      diagnosis of spinal instability after trauma, but no conclusive system was
      established. Those systems were mostly based on experiments performed on spinal
      segments after sequential ablation of ligaments and facet joints followed by
      static, unidirectional physiologic loading. We believed that there was a need for
      more profound knowledge of spinal injury and for instability criteria of lumbar
      spinal injuries based on more realistic experimental data simulating the clinical
      situation. In our injury model, we decided to study the biomechanic outcome of a
      flexion-distraction injury similar to seatbelt type injury seen in frontal motor
      vehicle collisions. METHODS: Twenty lumbar functional spinal units were first
      loaded statically with a physiologic flexion-shear load to determine angulations
      and displacements under noninjurous conditions. Dynamic flexion-shear loading to
      injury with two different load pulses was then applied. Static physiologic load
      was then again applied to determine any permanent residual deformation. RESULTS:
      The viscoelastic effect of loading rate on translatory and angular displacements
      and the values for translatory and angulation displacements at first sign of
      injury (yield) and at failure were determined. CONCLUSIONS: Radiographic
      guidelines for instability criteria in lumbar and thoracolumbar fracture
      dislocations without concomitant posterior vertebral body compression are
      proposed: 1. Instability exists if there is a kyphosis of the lumbar motion
      segment > or = 12 degrees (impending instability) or > or = 19 degrees (total
      instability) on lateral radiographs. 2. Relative increase in interspinous process
      distance > or = 20 mm (impending instability), > or = 33 mm (total instability)
      on anteroposterior radiographs.

PMID- 7638654
TI  - Validity of the three-column theory of thoracolumbar fractures. A biomechanic
      investigation.
AB  - STUDY DESIGN: This study validated the three-column theory of fractures by
      correlating the multidirectional instabilities and the vertebral injuries to each
      of the three columns, using a biomechanic trauma model. OBJECTIVES: The objective
      was to validate the three-column theory as applied to the thoracolumbar
      fractures. SUMMARY OF BACKGROUND DATA: The widely used three-column theory of
      fractures for classification and evaluation was based on retrospective analysis
      of radiographs. No biomechanic study, using realistic spinal fractures and
      multidirectional instability measurements, was available. METHODS: Using 16 fresh
      cadaveric thoracolumbar human spine specimens, two groups of burst fractures were
      produced by either simple axial compression or flexion-compression, using a high
      speed trauma model. Multidirectional flexibility was measured before and after
      the trauma, thus quantifying the instability of the burst fracture. Computed
      tomography scans were taken after the fracture, and a newly developed injury
      scoring scheme quantified the injuries to the anterior, middle, and posterior
      columns. Statistical correlations were obtained between the flexibility
      parameters and injuries to each of the three columns. RESULTS: In the axial
      compression group, the middle column injury, compared with the other two columns,
      showed the highest correlations to eight of the nine flexibility parameters
      (average R2 = 0.77). In the flexion-compression group, again the middle column
      injury showed the highest correlations to eight of the nine flexibility
      parameters (average R2 = 0.85). CONCLUSIONS: The results of this study supported
      the three-column theory of the thoracolumbar fractures and bolstered the concept
      of the middle column being the primary determinant of mechanical stability of
      this region of the spine.

PMID- 7638655
TI  - Natural course of cervical spine lesions in rheumatoid arthritis.
AB  - STUDY DESIGN: This study analyzed the natural course of cervical spine
      involvement in rheumatoid arthritis by serial radiographs. OBJECTIVES: The
      purpose was to determine the pattern of progression of cervical spine lesions in
      rheumatoid arthritis and predictors for the extent of progression. SUMMARY OF
      BACKGROUND DATA: Subluxation frequently occurs as a result of rheumatoid
      involvement of the cervical spine. It may be severe in patients with mutilans
      deformities in the hands and feet. The extent of progression in a given patient
      is still unpredictable. METHODS: Serial cervical radiographs in 49 patients with
      rheumatoid arthritis were analyzed. The extent of progression was evaluated by
      rheumatoid arthritis subset defined previously, which reflected the final extent
      of joint erosion in this systemic disease and could be roughly classified during
      early stages of the disease. RESULTS: In the upper cervical spine, reducible
      anterior atlantoaxial subluxation occurred first. Vertical subluxation of the
      axis appeared next. Irreducible change of preceding anterior atlantoaxial
      subluxation was a sign of the start of vertical subluxation. In subaxial lesion,
      subluxation occurred less frequently (22.4%) than upper cervical lesion (77.6%).
      The extent of progression was different with the rheumatoid arthritis subset. In
      the upper cervical spine, none of the subset with least erosive disease developed
      vertical subluxation, whereas 52% of the subset with more erosive disease and 88%
      of the subset with mutilating disease advanced to vertical subluxation. The
      extent of progression was well correlated with the number of joints with erosion.
      Subaxial subluxation was often seen and became irreducible in mutilating disease
      and more erosive disease, but not in least erosive disease. CONCLUSIONS: A
      progressive pattern of the upper cervical subluxations was clarified. That is,
      upper cervical lesions progressed from reducible anterior atlantoaxial
      subluxation to irreducible anterior atlantoaxial subluxation with vertical
      subluxation. This extent of progression was different with the rheumatoid
      arthritis subset, which was also related to the development of subaxial
      subluxation. The most aggressive arthritis classification, a subset with
      mutilating disease, had the more severe subluxation in both upper and subaxial
      cervical spine.

PMID- 7638656
TI  - Incidence of acute care complications in vertebral column fracture patients with
      and without spinal cord injury.
AB  - STUDY DESIGN: This study retrospectively analyzed vertebral column fractures in
      trauma patients during a 2-year period. Data from a multicenter trauma registry
      were used. OBJECTIVES: The purpose of this study was to ascertain and describe
      the initial in-hospital morbidity and mortality rates for patients with vertebral
      column fractures with and without spinal cord injury. SUMMARY OF BACKGROUND DATA:
      Patients with vertebral fractures and associated spinal cord injuries experience
      more medical complications than those without spinal cord injuries. However, the
      precise incidence and relative risk of complications during acute care
      hospitalization for these two groups are not well documented. METHODS: Vertebral
      column fractures in 419 adolescent and adult trauma patients hospitalized during
      a 2-year period were retrospectively analyzed using data from a multicenter
      trauma registry. RESULTS: Of the 419 patients, 104 (24.8%) had an associated
      spinal cord injury. More than half of the spinal cord injury patients (52.9%) and
      20.6% of those without spinal cord injury had one or more complications during
      their hospitalization. Complications resulted in an average of 33.1 extra
      hospital days, which extrapolates nationally into 1.5 million additional days
      annually. The four complications differing most significantly in incidence
      between the spinal cord injury group and the non-spinal cord injury group were:
      urinary tract infections (24.0% vs. 8.6%), respiratory (23.1% vs. 8.6%), cardiac
      (11.5% vs. 3.2%), and decubitus ulcer (7.7% vs. 1.0%). Pneumonia, although not
      statistically different, was high in both groups (13.5% vs. 7.3%). CONCLUSIONS:
      The incidence of the 25 types of medical complications reported here provides
      specific and relevant information to assist health professionals in treating
      patients during their acute care. We estimate that complications during initial
      hospitalization add $1.5 billion annually to the cost of caring for patients with
      vertebral fractures in the United States.

PMID- 7638657
TI  - Interpretation of abnormal lumbosacral spine radiographs. A test comparing
      students, clinicians, radiology residents, and radiologists in medicine and
      chiropractic.
AB  - STUDY DESIGN: Controlled comparison of radiographic interpretive performance
      based on training and experience. OBJECTIVES: This study compared each of these
      groups in medicine and chiropractic by testing abilities to interpret abnormal
      plain film radiographs of the lumbosacral spine and pelvis. SUMMARY OF BACKGROUND
      DATA: Low back pain is a common and costly problem that is evaluated and treated
      primarily by medical physicians, orthopedists, and chiropractors. Although
      radiology is used extensively in patients with low back pain, the radiographic
      interpretations of students, clinicians, radiology residents, and radiologists
      have never been compared. METHODS: Four hundred ninety-six eligible volunteers
      from nine target groups completed a test of radiographic interpretation
      consisting of nineteen cases with clinically important radiographic findings. The
      nine groups included 22 medical students, 183 chiropractic students, 27 medical
      radiology residents, 13 chiropractic radiology residents, 66 medical clinicians
      (including 12 general practice physicians, 25 orthopedic surgeons, 21 orthopedic
      residents, and 8 rheumatologists), 46 chiropractic clinicians, 48 general medical
      radiologists, 55 chiropractic radiologists, and 36 skeletal radiologists and
      fellows. RESULTS: The test established a high level of internal consistency
      reliability (0.880) and revealed that, in the interpretation of abnormal plain
      film radiographs of the lumbosacral spine and pelvis, significant differences
      were found among professional groups (P < 0.0001). Post hoc tests (P < 0.05)
      revealed that skeletal radiologists achieved significantly higher test results
      than did all other medical groups; that the test results of general medical
      radiologists and medical radiology residents was significantly higher than those
      of medical clinicians; that test results of medical students was significantly
      poorer than that of all other medical groups; that the performance of
      chiropractic radiologists and chiropractic radiology residents was significantly
      higher than that of chiropractic clinicians and chiropractic students; that no
      significant differences was revealed in the mean values of performance of
      chiropractic clinicians and chiropractic students; that the test results of
      chiropractic radiologists, chiropractic radiology residents, and chiropractic
      students was significantly higher than that of the corresponding medical
      categories (general medical radiologists, medical radiology residents, and
      medical students, respectively); that no significant difference in test results
      was identified between chiropractic radiologists and skeletal radiologists or
      between chiropractic and medical clinicians; and that the length of time in
      practice for clinicians and radiologists was not a significant factor in the test
      results. CONCLUSIONS: These data demonstrate a substantial increase in test
      results of all radiologists and radiology residents when compared to students and
      clinicians in both medicine and chiropractic related to the interpretation of
      abnormal radiographs of the lumbosacral spine and pelvis. Furthermore, the study
      reinforces the need for radiologic specialists to reduce missed diagnoses,
      misdiagnoses, and medicolegal complications.

PMID- 7638658
TI  - Clinical correlates of patient satisfaction after laminectomy for degenerative
      lumbar spinal stenosis.
AB  - STUDY DESIGN: Prospective multicenter observational study of the outcome of
      surgery for degenerative lumbar spinal stenosis. OBJECTIVES: To identify
      correlates of patient satisfaction with the results of surgery. SUMMARY OF
      BACKGROUND DATA: Little published information exists on correlates of patient
      satisfaction after surgery for spinal stenosis. METHODS: Preoperative and 6-month
      follow-up data for 194 patients were analyzed. Associations between preoperative
      variables and satisfaction with the results of surgery were examined in
      univariate and multivariate models. RESULTS: In multiple linear regression models
      that adjusted for the effects of age, gender, individual surgeon, number of
      interspaces decompressed, whether a fusion was performed, depression score, and
      overall level of pain, the predominance of back (as opposed to leg) pain, greater
      comorbidity, and worse preoperative functional status were associated with lower
      patient satisfaction. The regression model explained just 15% of the variance in
      patient satisfaction. CONCLUSIONS: Patients bothered predominantly by back pain
      preoperatively and those with greater medical comorbidity and functional
      disability are significantly less satisfied with the results of surgery for
      degenerative lumbar spinal stenosis.

PMID- 7638659
TI  - Observations on the pathomorphology of the thoracolumbar fascia in chronic
      mechanical back pain. A microscopic study.
AB  - STUDY DESIGN: Human tissue specimens were examined for the presence of neural end
      organs under light and electron microscopy. OBJECTIVES: To define the innervation
      of the thoracolumbar fascia in problem back pain patients who have articular
      abnormality defined through pain-provocation discography or facet blocks. SUMMARY
      OF BACKGROUND DATA: Previous investigators have defined the presence of
      innervation in control (no back pain) tissue specimens. METHODS: Tissue specimens
      were harvested during surgery from 24 back pain patients who had not undergone
      previous lumbar surgery. Specimens were fixed immediately in the operating room
      and later processed and studied under light and electron microscopy. RESULTS:
      Structural and ultrastructural studies failed to identify specific neural end
      organs in any of the specimens. Serendipidously, microscopic changes suggestive
      of ischemia or inflammation in this tissue were found. CONCLUSIONS: These
      findings suggest that the thoracolumbar fascia may be deficiently innervated in
      problem back pain patients.

PMID- 7638660
TI  - Impact of a medical back care program on utilization of services and primary care
      physician satisfaction in a large, multispecialty group practice health
      maintenance organization.
AB  - STUDY DESIGN: Samples of patients with new back pain were compared at two medical
      centers, one with and one without a medical back care program. OBJECTIVES: To
      measure the impact of a medical back care program on use of services and
      physician satisfaction in a health maintenance organization. SUMMARY OF
      BACKGROUND DATA: A medical back care program is staffed with specially trained
      primary care physicians and provides consultative and educational services to the
      medical center. METHODS: Program impact on services was measured by comparing the
      number of physician office visits, consultations, physical therapy referrals, and
      imaging procedures provided to a sample of patients with back pain at the two
      medical centers. Physician satisfaction with care provided to patients with back
      pain was measured by a survey sent to primary care physicians at both medical
      centers. RESULTS: At the medical center with a back care program, 42% fewer
      consultations, 59% fewer physical therapy referrals, and 33% fewer imaging
      procedures were ordered. Less expensive consultations with back care physicians
      in medicine or family practice were ordered more frequently than consultations
      with either neurologists or orthopedists. This change in pattern of care took
      place without significantly altering clinical course. The effect of the program
      on the rate of surgery was not measured. CONCLUSIONS: The results of this study
      support the benefits of an organized medical back care program.

PMID- 7638661
TI  - Effects of tiaprofenic acid and indomethacin on proteoglycans in the degenerating
      porcine intervertebral disc.
AB  - STUDY DESIGN: Eighteen pigs were stabbed with a scalpel in the anterior part of
      the anulus fibrosus of a lumbar disc. After surgery, the pigs received either
      tiaprofenic acid or indomethacin daily, and a third group did not receive any
      medication. OBJECTIVES: Nonsteroidal anti-inflammatory agents are widely used in
      the treatment of low back patients, but their long-term effects on the matrix
      molecules in the degenerate disc are unknown. SUMMARY OF BACKGROUND DATA: Several
      in vitro and in vivo studies on articular cartilage have suggested that
      tiaprofenic acid may not have adverse effects on matrix metabolism, whereas
      indomethacin probably does. METHODS: Uronic acid, DNA, and water contents were
      determined from five different locations in each injured disc. Transport and
      incorporation of sulfate were examined by in vivo radioactive tracer analysis,
      and proteoglycan structures were analyzed by gel electrophoresis. RESULTS:
      Morphologically, there were no differences between the treatments. Tiaprofenic
      acid maintained a higher uronic acid content in the nucleus pulposus and outer
      anulus compared with that of the nonmedicated animals. Tiaprofenic acid decreased
      the incorporation of sulfate in the injured area and the water content at most
      sites. Indomethacin had no adverse effects compared with the nonmedicated group,
      and it increased water content in the posterior anulus fibrosus. CONCLUSIONS:
      Long-term administration of tiaprofenic acid and indomethacin did not have
      harmful effects on matrix metabolism after disc injury. On the contrary,
      tiaprofenic acid may slightly protect proteoglycans in the degenerating disc.

PMID- 7638662
TI  - Lumbar spinal stenosis. Clinical and radiologic features.
AB  - STUDY DESIGN: A prospective, randomized study of patients with symptomatic lumbar
      spinal stenosis. OBJECTIVES: Evaluation of clinical and radiologic
      characteristics and relationship. SUMMARY OF BACKGROUND DATA: The diagnosis of
      lumbar spinal stenosis is frequently used and represents a wide variety of
      patients with more or less well-defined spinal disorders. METHODS: One hundred
      patients who met inclusion criteria were consecutively selected from a neurology
      department and examined clinically and radiologically with plain radiography,
      myelography, and computed tomographic imaging. RESULTS: Duration of complaints
      was long, and multilevel, bilateral afflictions were common. The dominanting
      symptoms were sciatica, neurogenic claudication, and low back pain. The clinical
      findings were modest. Narrowness in the spinal canal was demonstrated
      radiologically with signs of compression on nerve roots, centrally and/or
      laterally. The radiologic findings were more extensive than expected from the
      clinical symptoms and signs. In most patients the sagittal diameter of the spinal
      canal increased on flexion and decreased on extension of the spine. An exception
      was demonstrated in 33 patients where extension increased the diameter, usually
      at one level. Radiologic subgroups of stenosis were found, but their clinical
      relationship could hardly be identified. No definite association between the
      degree of narrowing and clinical symptoms was found. CONCLUSIONS: A clinical
      picture is demonstrated in 100 patients with symptomatic lumbar spinal stenosis.
      Different types of stenosis are found radiologically, but their clinical
      relationships are not identified. The radiologic changes were more extensive than
      expected from the clinical picture, and the degree of narrowing did not
      correspond to the degree of clinical affliction.

PMID- 7638663
TI  - The effects of a work hardening program on cardiovascular fitness and muscular
      strength.
AB  - STUDY DESIGN: This study analyzed improvements in cardiovascular fitness and
      muscular strength after a 6-week work hardening program. OBJECTIVES: The
      objective of this study was to document fitness gains after a 6-week work
      hardening program. SUMMARY OF BACKGROUND DATA: Studies expounded on the success
      of a functional restoration approach in return-to-work rates, but few documented
      the physical fitness gains of a work hardening program. METHODS: Thirty-one
      subjects from the Rehability Center in Lubbock, Texas, who were diagnosed with
      lower back dysfunction, completed the 6-week study. A submaximal cycle ergometer
      protocol was used to determine patients' cardiovascular fitness levels, and the
      Arcon Static Strength Testing Device was used to measure static strength. Pre-
      and post-tests were identical. RESULTS: A paired Student's t test was used to
      analyze the significance of difference from pre- to post-testing. For
      cardiovascular fitness there was a 28% improvement, t(29) = 5.56, P < 0.001;
      there was a 76% improvement for the static arm lift, t(29) = 7.86, P < 0.001;
      there was a 57% improvement in the static pull, t(29) = 9.53, P < 0.001; and an
      89% improvement in the static push, t(29) = 9.08, P < 0.001. CONCLUSIONS:
      Analyzed data clearly show a marked improvement in cardiovascular and muscular
      fitness. There was not a difference in fitness levels between those who returned
      to work and those who did not, which suggests return-to-work rates are not
      entirely based on level of fitness.

PMID- 7638664
TI  - Chronic sciatica caused by tuberculous sacroiliitis. A case report.
AB  - STUDY DESIGN: This is a case report. OBJECTIVES: To report and discuss a case of
      tuberculosis sacroiliitis with anterior synovial cyst presenting as chronic
      sciatica. SUMMARY OF BACKGROUND DATA: This is a report of clinical manifestation,
      physical findings, computed tomography scan, and results after surgical treatment
      in a 58-year-old woman with tuberculous sacroiliitis, which caused chronic
      sciatica. METHODS: The physical findings, laboratory data, radiographs, and
      computed tomography scan of sacroiliac joints were studied. Sacroiliitis with
      anterior synovial cyst was shown in computed tomography scan. Posterior
      arthrotomy and drainage of the synovial cyst were performed. After surgery, she
      was treated with three combined antituberculosis drugs for 9 months. RESULTS:
      Lowenstein-Jensen culture and histologic examination confirmed the diagnosis of
      tuberculous sacroiliitis. At 3 years, she had no back pain or sciatica and a
      complete functional recovery. CONCLUSIONS: Tuberculous sacroiliitis with anterior
      synovial cyst is a rare cause of chronic sciatica. Lateral compression of the
      pelvis, Gaenslen's test, and Patrick's test should be included in evaluation of
      patients with sciatica. Computed tomography scan is a superb diagnostic method
      for sacroiliitis. Arthrotomy and drainage effectively relieve the sciatica. Three
      combined antituberculosis drug therapy should be given after surgery.

PMID- 7638665
TI  - Marfan syndrome with back pain secondary to pedicular attenuation. A case report.
AB  - STUDY DESIGN: This is a report of a 31-year-old woman with Marfan syndrome with
      severe back pain secondary to pedicle fractures of the lumbar spine resulting
      from attenuation of the pedicles. OBJECTIVES: To report and discuss a case of
      Marfan syndrome. SUMMARY OF BACKGROUND DATA: The authors report the clinical
      course of a patient with Marfan syndrome and pedicle fractures secondary to
      thinning of the pedicles. METHODS: After initial diagnosis of Marfan syndrome was
      confirmed, radiologic techniques, including magnetic resonance imaging and bone
      scan, were used to evaluate any abnormalities of the lumbar spine. RESULTS: The
      patient was treated with pain medications and activity modification, which
      allowed for no marked improvement. CONCLUSIONS: Thinning and possible fracturing
      of the pedicles should be considered as an etiology of back pain in the patient
      with Marfan syndrome.

PMID- 7638666
TI  - Intramedullary spinal cord abscess. A case report.
AB  - STUDY DESIGN: A case of an intramedullary spinal cord abscess is presented. The
      literature on this subject is carefully reviewed. OBJECTIVES: To give an overview
      of clinical presentation, radiographic examination, pathogenesis, treatment, and
      outcome of intramedullary spinal cord abscesses. Cases presented in the
      literature are arranged and the findings summarized. SUMMARY OF BACKGROUND DATA:
      Intramedullary spinal cord abscesses are rare. Most frequently, single cases were
      reported, followed by a short discussion. All previously reported cases were
      reviewed. METHODS: After an extensive literature search, all cases of an
      intramedullary spinal cord abscess (totaling 93 patients), including ours, were
      reviewed. Incidence, clinical presentation, neuroradiologic investigations,
      treatment, and pathogenesis are discussed. RESULTS: Intramedullary spinal cord
      abscesses are rare. The presentation can be very confusing, mimicking thoracic or
      abdominal diseases. Magnetic resonance imaging is the best diagnostic technique,
      although the findings are not pathognomonic. Appropriate antibiotic therapy after
      surgical drainage is warranted. If left untreated, the outcome is bleak. Whereas
      most cultures remain sterile (38.7%), Staphylococcus or Streptococcus species are
      involved frequently (23.7% and 17.2%). CONCLUSIONS: Although intramedullary
      spinal cord abscess is a rare disease, every spine surgeon should have knowledge
      of its existence because misjudgment and deferring adequate treatment may lead to
      an unfavorable outcome.

PMID- 7638667
TI  - Cavernous angioma of the upper cervical spinal cord. A case report.
AB  - STUDY DESIGN: The treatment of a patient with progressive neurologic deficit
      secondary to a cavernous angioma located in the dorsal midline of the upper-most
      cervical spinal cord was described. OBJECTIVES: An illustrative case of a patient
      with an exophytic cavernous angioma of the cervical spinal cord near the
      cervicomedullary junction was presented, the literature reviewed, and the
      treatment of these patients discussed. SUMMARY OF BACKGROUND DATA: Cavernous
      angiomas of the spinal cord were rarely seen, and only more recently appreciated
      with the advent of MRI scanning. These lesions were usually intramedullary in
      location. Intradural extramedullary cavernous angiomas, or intramedullary lesions
      with exophytic extramedullary extension, were particularly rare and usually
      occurred at the cauda equina. METHODS: The surgical treatment of a patient with
      an exophytic cavernous angioma of the upper cervical spinal cord was presented.
      RESULTS: This patient underwent surgery after a hemorrhage that occurred after
      the patient was treated conservatively for several years. The entire lesion was
      resected with standard microsurgical technique, and the neurologic symptoms
      subsequently resolved. CONCLUSIONS: This entity should be suspected in the
      differential diagnosis of patients with progressive and step-wise deterioration
      of spinal cord function. Although these patients can be treated conservatively,
      those with progressive neurologic deficits should undergo microsurgical resection
      to avert subsequent lesion enlargement or repeated hemorrhage.

PMID- 7638668
TI  - Computer-assisted pedicle screw fixation. A feasibility study.
AB  - STUDY DESIGN: We evaluated a computer-assisted surgical tool for inserting
      pedicle screws. OBJECTIVES: This study reviewed the feasibility, usefulness, and
      accuracy of the proposed tool. SUMMARY OF BACKGROUND DATA: Reviews documented
      neurovascular damage caused by screw misplacement. Currently, screw hole position
      is assessed by radiologic means and curette palpation. METHODS: Three sheep
      vertebrae and one artificial object were reconstructed three-dimensionally from
      computed tomography scan slices. At surgery, the surgeon's movements were
      displayed relative to the three-dimensional vertebrae on a computer screen. The
      tool was used to detect pedicles and to verify the position of drilled holes. In
      our laboratory, we calculated the system's accuracy by taking measurements on the
      artificial object. RESULTS: All pedicles were identified with the computer. Five
      of the six drilled hole positions were correctly represented. An accuracy of 4.5
      mm +/- 1.1 mm RMS (root of the mean squared) and 1.6 degrees +/- 1.2 degrees were
      calculated. CONCLUSIONS: Results suggested the proposed system could be useful
      for pedicle detection and assessing the intravertebral location of a drilled
      hole. The proposed system could be used for many different orthopedic procedures
      where structures are hidden from the surgeon's view.

PMID- 7638669
TI  - Outcome of lumbar fusion in Washington State workers' compensation.

PMID- 7638670
TI  - [Tumor-induced occlusive jaundice--strategy of interventional drainage
      techniques].

PMID- 7638671
TI  - [Contrast medium-assisted storage film-screen radiography on the intensive care
      unit].

PMID- 7638672
TI  - [Computerized tomography of mediastino-retroperitoneal angiomatosis].

PMID- 7638673
TI  - [Granular cell tumor of the breast--a rare differential diagnosis of breast
      carcinoma].

PMID- 7638674
TI  - [Complicated appendicitis in a caudal cecum--ectopically displaced normal
      roentgen markers].

PMID- 7638675
TI  - Universal infant immunisation for hepatitis B--from dream to reality.

PMID- 7638677
TI  - Cost-containment through shared responsibility.

PMID- 7638676
TI  - Planning rational management of chronic diseases--lessons from a lipid clinic.

PMID- 7638678
TI  - Making research more relevant--is health systems research the answer?

PMID- 7638679
TI  - Monetarism and health.

PMID- 7638680
TI  - Issues affecting the reform of prison health care in South Africa.

PMID- 7638681
TI  - Conceptualising health services in terms of level and location of care--a view
      from the academic health complex.
AB  - The origin and characteristics of academic health complexes (AHCs) are briefly
      outlined, along with pressures for restructuring of health services towards
      primary levels of care within the primary health care (PHC) approach. Weaknesses
      and strengths of the AHCs together with imbalances in the overall health system
      of which they are part are discussed. The Cape Town AHC is used to exemplify a
      suggested framework for analysis and development of other AHCs in South Africa
      and their transformation in accordance with the PHC approach. A method of service
      mapping is employed to aid an appreciation of the complexity of AHC services.
      Planning for potential transformation may be facilitated by conceptualising
      services in two dimensions, viz. level and location of care. Two important
      additional dimensions of service component linkage are integration across levels
      of care along a vertical axis, and integration across different services at
      primary level along a horizontal axis (comprehensiveness). AHCs, however skewly
      developed in terms of level and location of care, are complex combinations of
      services. They encompass all levels of care provided both within and beyond the
      walls of multiple health care facilities which are located both centrally and
      peripherally. AHC services are managed by health professionals in specific
      academic disciplines. They include PHC functions at the interface between primary
      and specialist care provision, and community health functions which are
      principally located outside the health care facilities in the community.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7638683
TI  - Familial defective apolipoprotein-B is rare in hypercholesterolaemic South
      African Afrikaners, coloureds and Indians.
AB  - The frequency of familial defective apolipoprotein B-100 (FDB) was assessed among
      hypercholesterolaemic Afrikaners, coloureds and Indians. Patients selected for
      screening did not carry any of the founder or common LDL-receptor mutations known
      to be associated with these groups. No FDB was detected and the mutation is
      therefore a rare cause of hypercholesterolaemia in these South African
      populations.

PMID- 7638682
TI  - Perinatal mortality in the Cape Province, 1989-1991.
AB  - OBJECTIVE: To determine the number of deliveries, the low-birth-weight rate and
      the perinatal mortality rate at provincial and province-aided hospitals and
      clinics in each planning region of the Cape Province. DESIGN: A record of the
      number of deliveries, low-birth-weight infants, stillbirths and early neonatal
      deaths in provincial and province-aided hospitals and clinics in each planning
      region of the Cape Province between 1 January 1989 and 31 December 1991. SETTING:
      All provincial and province-aided hospitals and clinics in the Cape Province.
      PARTICIPANTS: Hospital and clinic staff of all provincial and province-aided
      hospitals and clinics in the Cape Province. MAIN OUTCOMES MEASURED: Number of
      deliveries, low-birth-weight infants, stillbirths and early neonatal deaths in
      each planning region of the Cape Province. RESULTS: A total of 373,768 births
      were recorded during the 3-year period with a low-birth-weight rate of 14.7%, a
      stillbirth rate of 17.9 per 1,000 and an early neonatal mortality rate of 9.1 per
      1,000. All rates differed widely between regions. The regions with the highest
      perinatal mortality rates were in the northern and eastern Cape. CONCLUSION: The
      perinatal demographics of most regions in the Cape Province are typical of a
      developing country. Regions which have been identified as having the highest low
      birth-weight, stillbirth and early neonatal mortality rates are in greatest need
      of improved perinatal health care.

PMID- 7638684
TI  - Recurrent LDL-receptor mutation causes familial hypercholesterolaemia in South
      African coloureds and Afrikaners.
AB  - Three low-density lipoprotein receptor (LDLR) gene mutations were previously
      shown to cause familial hypercholesterolaemia (FH) in up to 90% of affected
      Afrikaners. Association of each mutation with a single chromosomal background
      provided molecular genetic evidence that the proposed 'founder gene effect' was
      responsible for the high prevalence of FH among white Afrikaners. In this study
      we report the identification of the FH Afrikaner-2 (FH2) mutation, Val408 to Met,
      in the so-called coloured population of South Africa, a people of mixed ancestry,
      with rapid non-radioactive methods for mutation detection. Haplotype analysis
      with polymorphisms on both sides of the FH2 mutation indicated that the identical
      LDLR gene mutations found in two different South African population groups were
      caused by independent events at a potential CpG mutational 'hot spot'. The
      allelic variation giving rise to the different chromosomal backgrounds of the FH2
      mutation does not affect the properties of the abnormal LDLR protein product
      which causes FH in these subjects. This mutation is thus expected to cause the
      same severe form of FH in affected coloureds as was previously demonstrated in
      Afrikaners. Detection of mutant LDLR gene alleles in polymerase chain reaction
      products, directly after gel electrophoresis, now allows accurate presymptomatic
      diagnosis of the FH2 mutation in FH patients from two different South African
      population groups.

PMID- 7638685
TI  - Supplemented low-protein diets--are they superior in chronic renal failure?
AB  - Twenty-two patients with chronic renal failure were randomly assigned to a
      conventional low-protein diet containing 0.6 g protein/kg/day or a very-low
      protein diet containing 0.4 g protein/kg/day supplemented with essential amino
      acids; they were followed up for 9 months. There were no significant changes in
      body mass index, arm muscle area, percentage body fat, serum albumin and
      transferrin levels in any of the groups; neither was there any difference between
      the groups in respect of these parameters. Renal function, as measured by the
      reciprocal of serum creatinine over time, stabilised in both groups during
      intervention, with no significant difference between the groups. There was
      however no correlation between changes in renal function and changes in blood
      pressure, or dietary intake of protein, phosphorus, cholesterol, polyunsaturated
      and saturated fatty acids. There were also no significant changes and no
      significant differences between the groups in serum levels of parathyroid hormone
      and alkaline phosphatase, urine cyclic adenosine monophosphate, tubular
      reabsorption of phosphate, and the theoretical renal threshold for phosphate. The
      results of this study suggest that the supplemented very-low-protein diet was not
      superior to the conventional low-protein diet in terms of its effect on protein
      energy status, renal function and biochemical parameters of renal osteodystrophy.

PMID- 7638686
TI  - Expenditure on health research in South Africa, 1991/1992.
AB  - OBJECTIVE: To determine expenditure on health research in South Africa in
      1991/1992. DESIGN: Data from the financial statements of large statutory councils
      conducting research in South Africa, as well as other relevant reports,
      particularly the Department of National Education's (NATED) survey of research
      institutions, were analysed. RESULTS: A total of R198.7 million was spent on
      health research in 1991/1992, 56.1% by the tertiary education sector and 20.7% by
      the Medical Research Council. Only 1.1% of expenditure on health was spent on
      research. Less than 9% of health research expenditure by tertiary educational
      institutions is classified within the category of 'comprehensive medicine' (which
      includes community health, epidemiology and nutrition), whereas 82% of
      expenditure by autonomous government institutions is so classified. CONCLUSIONS:
      Given that expenditure on health research in South Africa is relatively low by
      international standards, an increase in expenditure by both the public and
      private sectors should be considered. Given the scarcity of research resources,
      there should be adequate planning, co-ordination, and particularly prioritisation
      of resource allocations, so that research can be directed towards addressing the
      country's health needs.

PMID- 7638687
TI  - Research on human reproduction and the United Nations.
AB  - The Special Programme of Research, Development and Research Training in Human
      Reproduction was established in 1972 by the World Health Organisation to promote,
      co-ordinate, support, conduct and evaluate research on human reproduction with
      particular reference to the needs of developing countries. Today, the Programme
      is the main instrument of reproductive health research in the United Nations
      System. In addition to advising member state governments, the Programme supports
      research and development activities in the areas of technology assessment,
      development, introduction and transfer, epidemiological and social science
      research on reproductive health and essential national health research. Another
      important area of activity consists of strengthening the research capability of
      developing countries to enable them to address reproductive health problems of
      national relevance.

PMID- 7638688
TI  - Failure to thrive and its relationship to serum vitamin A levels and diet.
AB  - Serum vitamin A and retinol-binding protein (RBP) levels were determined in a
      group of 34 children between 1 and 4 years of age with failure to thrive and in
      34 age- and sex-matched controls. Both groups of children were also assessed in
      respect of anthropometry and diet. Vitamin A levels in patients (0-32.2
      micrograms/100 ml; median 16.9 micrograms/100 ml) did not differ significantly
      from controls (6.4-47.2 micrograms/100 ml; median 16.1 micrograms/100ml).
      Fourteen patients (42%) and 4 controls (12%) had vitamin A levels below 10
      micrograms/100 ml. RBP levels in patients (0.45-3.50 mg/100 ml; median 2.17
      mg/100 ml) also did not differ significantly from those in controls (1.21-3.66
      mg/100 ml; median 2.06 mg/100 ml). No clinical features of vitamin A deficiency
      were detected. Weight and height for age, weight for height, mid-upper arm
      circumference and head circumference differed significantly between patients and
      controls (P < 0.0001 in each instance). Although within the recommendations for
      intake, patients had a significantly lower intake of the essential fatty acid C
      18:2 (N = 6) (linoleic acid) and vitamin A. In view of the current proposed
      relationship between vitamin A status and infectious diseases, the prevalence of
      biochemical vitamin A deficiency in children in the Cape Town community studied
      may contribute to the morbidity and mortality associated with infectious diseases
      in the area to a greater degree than has been suspected.

PMID- 7638689
TI  - Private beneficence for public profit--the Cecil John Adams Travelling
      Fellowship.

PMID- 7638690
TI  - Universal precautions for the prevention of HIV and HBV infection in health care
      settings. Committee for Science and Education, Medical Association of South
      Africa.
AB  - OBJECTIVE: To outline the principles guiding the deliberate actions that should
      be taken in health care settings to prevent the spread of pathogens, especially
      HIV and hepatitis B virus (HBV), to patients and health care workers (HCWs).
      OUTCOMES: Universal precautions should be implemented in all health care
      settings. EVIDENCE: Based on similar international recommendations. VALUES: An
      adaptation of an existing guideline, it was sent to 87 organisations for comment.
      The comments received were included where possible in this guideline. It is the
      right of HCWs and patients to be protected from nosocomial HIV and HBV infection.
      BENEFITS, HARMS AND COSTS: The prevention of costly HIV and HBV infection by
      simple, rational precautions in the health care setting. The cost to the health
      care system has not been measured. The cost to individual patients or HCWs who
      acquire either infection is inestimable. RECOMMENDATIONS: The guideline
      recommends that the four basic elements of universal precautions be implemented
      appropriately in all health care settings: (i) body fluids should be handled with
      the same precautions as blood; (ii) avoidance of sharps (sharp objects); (iii)
      avoidance of skin or mucous membrane contamination; (iv)
      cleaning/disinfecting/sterilising. VALIDATION: The draft guideline was subjected
      to extensive external review by specialist, generalist and health professional
      groups. These included HIV activist groups. There were no major disputes about
      the content. The most important amendment to the draft guideline is the inclusion
      of HBV and other related pathogens together with the HIV. DEVELOPMENT AND
      FUNDING: The Medical Association of South Africa Committee for Science and
      Education. ENDORSEMENTS: The MASA and twenty national health care organisations
      and three provincial health authorities (see list at end of document).

PMID- 7638697
TI  - Two cheers for public health in South Africa.

PMID- 7638696
TI  - Pravastatin versus simvastatin--what happens in the real world?

PMID- 7638698
TI  - Causes of massive hypercholesterolaemia.

PMID- 7638699
TI  - SA medical schools--are standards dropping?

PMID- 7638700
TI  - HIV testing and informed consent.

PMID- 7638701
TI  - Incidence of HIV infection in first-time blood donors.

PMID- 7638702
TI  - 'The Lion of Africa'. Interview by Jonathan Spencer Jones.

PMID- 7638703
TI  - Pathobiology of plaque modeling and complication.
AB  - The artery wall adapts to changes in wall tension and wall shear stress by means
      of enlargement and changes in both thickness and composition. The intima may
      participate in these changes, and these compensatory adaptive-reactive
      modifications continue in the presence of atherogenesis. Further understanding of
      the interaction of the evolving plaque with the artery wall and the associated
      effects of the physical forces associated with the circulation should provide new
      insights into the nature of plaque instability and into the outcome of direct
      interventions.

PMID- 7638704
TI  - Lipoprotein disorders as related to atherosclerotic cardiovascular disease.
AB  - Dyslipidemias to a varying degree represent an important risk factor for
      atherosclerotic cardiovascular disease. They are correctable if correctly
      diagnosed and adequately cared for. Success depends on the optimal interplay
      between physician and patient and on the support of a trained dietitian. This is
      an area of preventive cardiology that is likely to receive increasing attention
      in the future, with the expectation that a decrease in morbidity/mortality for
      atherosclerotic cardiovascular disease will ensue.

PMID- 7638705
TI  - Medical therapy of peripheral arterial occlusive disease.
AB  - Lowering the overall morbidity rate of peripheral vascular disease requires a
      systematic approach to the patient with atherosclerosis. This includes
      comprehensive assessments of risk factors, appropriate modifications of diet and
      lifestyle as well as an effective and sustaining exercise regimen. The role of
      new pharmacologic agents is discussed.

PMID- 7638706
TI  - Intermittent claudication. The natural history.
AB  - Intermittent claudication is a relatively common disorder, present in a subset of
      patients with lower extremity atherosclerotic disease. Although lower extremity
      morbidity rates are low, patients with claudication frequently have coexistent
      cardiovascular disease and are at significantly increased risk of adverse
      cardiovascular events. Data to support work-up for concomitant coronary artery
      disease in conservatively managed patients are not available; however, clinicians
      should consider the high prevalence of coronary artery disease when developing
      management strategies. Patients should be carefully selected for lower extremity
      interventional management given the generally benign lower extremity prognosis.
      Tobacco smokers should be urged to quit, owing to their higher rate of lower
      extremity and cardiovascular adverse outcomes. Functional outcomes after various
      treatment strategies have not yet been sufficiently studied in the claudicant.

PMID- 7638708
TI  - MR and spiral/helical CT imaging of lower extremity occlusive disease.
AB  - Magnetic resonance (MR) angiography and spiral CT angiography are promising new
      imaging modalities for evaluating patients with lower extremity arterial
      occlusive disease. Both techniques are less invasive than conventional
      angiography, and MR angiography has the additional advantages of not requiring
      iodinated contrast media or ionizing radiation. The basic principles of MR
      angiography and spiral CT angiography are reviewed with an emphasis on three
      dimensional display techniques. This is followed by a discussion of their
      clinical applicability toward the diagnosis and treatment planning of lower
      extremity arterial occlusive disease.

PMID- 7638709
TI  - Angioplasty and intravascular stents in peripheral vascular disease.
AB  - Advances in the technique as well as the technology of percutaneous angioplasty
      over the past 30 years have allowed the percutaneous treatment of many vascular
      lesions that previously required operative management. PTA, and more recently
      intravascular stents, have been shown to be effective, safe, and, in some cases,
      more cost effective than surgical options. Although patients need to be
      appropriately selected to optimize the treatment plan in individual cases, it is
      clear that percutaneous treatment, either alone or in combination with surgical
      procedures, offers a significant advancement in patient care. The success in
      treating iliac disease is perhaps the most convincing, but evidence is rapidly
      building to support infrapopliteal procedures, and, as further advances are made
      in technology, the role of such procedures in distal vessels may be expanded to
      include more patients. These procedures need to be prospectively evaluated not
      only for their efficacy, long-term result, and safety, but also for their cost
      effectiveness and cost relative to the proven surgical options.

PMID- 7638707
TI  - Noninvasive evaluation of the lower extremity arterial tree and graft
      surveillance.
AB  - The application of duplex ultrasonography in the evaluation of lower extremity
      arterial occlusive disease and in graft surveillance has enhanced significantly
      the vascular surgeon's diagnostic armamentarium. With continued refinements in
      gray scale image resolution, color flow, and spectral analysis, color duplex
      ultrasonography eventually will replace angiographic evaluation in carefully
      selected patients as the primary pre-interventional testing modality.

PMID- 7638710
TI  - Thrombolysis in the treatment of lower extremity occlusive disease.
AB  - The development of new thrombolytic agents and increased experience in the use of
      these drugs has enhanced limb salvage, especially in patients who have undergone
      multiple lower extremity bypass procedures. This article reviews the indications
      for such therapy and critically assesses both complications and efficacy of
      treatment.

PMID- 7638711
TI  - Preoperative cardiac risk management.
AB  - CAD is present in most patients with peripheral arterial disease and is the
      leading cause of morbidity and mortality after vascular operations. Clinical risk
      assessment attempts to identify those patients at low, intermediate, or high
      cardiac risk for adverse cardiac outcomes. Additional tests add little
      information to the estimates obtained by clinical scoring in patients at low
      risk. Patients with high cardiac risk scores are clearly at increased risk of
      experiencing postoperative complications, but further investigations are needed
      only if knowledge of the functional severity or degree of myocardial ischemia
      will alter subsequent management. In general, high-risk patients should proceed
      to coronary angiography, intensive perioperative monitoring, alteration in the
      planned operation, or avoidance of surgery altogether if indications are less
      than compelling. Those patients identified as intermediate risk by clinical
      scoring benefit most from additional tests. In these patients special studies or
      even coronary arteriography may be useful if the vascular surgery can be delayed
      until myocardial revascularization is completed. Practically, preoperative
      cardiac work-up must also consider the indication for surgery. Patients who have
      threatened limbs or ruptured aneurysms or are severely symptomatic cannot afford
      the time involved for obtaining additional tests. Moreover, the question of what
      to do with the information provided by special studies is problematic in these
      patients. For example, if significant symptomatic or asymptomatic CAD is present
      in a patient with a gangrenous foot, what is gained by the delay in lower
      extremity revascularization required when prophylactic CABG is performed? Reports
      supporting prophylactic CAD intervention are nonrandomized and uncontrolled. CABG
      and PTCA should be performed only on the merits of the patient's cardiac symptoms
      and coronary artery anatomy, not to enhance safety of the proposed vascular
      procedure, because advances in surgical and anesthetic techniques and
      intraoperative and postoperative monitoring have resulted in lower morbidity and
      mortality of elective vascular surgery.

PMID- 7638712
TI  - Choice of anesthesia and intraoperative monitoring for lower extremity
      revascularization.
AB  - The prevalence of significant coronary artery disease re-enforces the importance
      of careful preoperative and intraoperative management in patients undergoing
      lower extremity revascularization. This article presents a practical approach
      toward the evaluation of anesthetic risk and the proper use of anesthetic agents
      and monitoring devices to minimize morbidity. The role of general and regional
      anesthetic agents is discussed, and complications of both techniques are
      presented.

PMID- 7638713
TI  - Retroperitoneal aortoiliac reconstruction.
AB  - The retroperitoneal approach to the aorta and the iliac arteries provides
      excellent exposure for reconstruction of these vessels for aortoiliac occlusive
      disease. Furthermore, the weight of evidence in the literature indicates that
      this approach is associated with fewer complications, a shorter length of stay in
      the hospital, and lower costs. The major drawback to this approach at present
      appears to be a lack of familiarity with the technical aspects of this exposure.
      It is our hope that this article helps familiarize surgeons with this exposure
      and encourages them to use it more frequently for "routine" aortoiliac
      reconstruction.

PMID- 7638714
TI  - Aortofemoral bypass via transperitoneal approach.
AB  - The transperitoneal route remains the most widely used approach to the infrarenal
      abdominal aorta. The specific indications and techniques are reviewed in full
      detail. Special circumstances that require modifications of the standard
      operative approach are presented. Finally, current and expected results of
      aortofemoral bypass are discussed.

PMID- 7638715
TI  - Endoscopic in situ bypass.
AB  - The use of in situ vein bypass continues to increase. A major problem of these
      procedures has been wound complications resulting from the multiple lower
      extremity incisions. New endoscopic techniques for identifying and ablating valve
      cusps and side branches have been developed. As illustrated in this article,
      these techniques simplify the procedure, avoid extensive incisions, and can be
      used with confidence by experienced surgeons.

PMID- 7638716
TI  - Bypass grafts to the ankle and foot. A personal perspective.
AB  - Our experience and that of others indicate that the number of very distal bypass
      operations is growing. From the early 1970s, when we performed a few operations
      per year, our numbers have increased to 60 to 65 operations annually, about 20%
      of all infrainguinal open revascularizations. Amputation of one leg leaves a
      patient, should he survive for a few years, with a second limb that is at
      substantial risk of infection or gangrene. From over 20 years of experience with
      thousands of diabetic leg problems and approximately 600 paramalleolar bypasses,
      the following facts have emerged from our clinical practice. Primary pedal
      arterial arches are virtually never complete. This alone should not deter the
      surgeon from attempting paramalleolar bypass grafting. Clinical details such as
      neuropathy, sepsis, and general medical status and even family support should not
      be overlooked as "risk factors." The order of frequency for pedal distal
      anastomotic sites will be anterior tibial/dorsalis pedis, posterior tibial/common
      plantar artery, lateral plantar artery/medial plantar artery, and lateral tarsal
      artery. In each case the graft should be placed as proximal as possible on the
      vessel; tibial outflow should be considered. Use short grafts with distal inflow
      whenever possible. In the rare instance wherein no pedal target site is
      available, consider the isolated tibial segment. Failure of a very distal bypass
      procedure seldom results in an amputation that is more proximal than otherwise
      would have been required if no bypass were attempted. As a corollary, after
      sepsis is controlled and all lesions and amputations are healed, failure of the
      graft may spare the limb from further risk of amputation. In diabetics, the
      presence of a palpable popliteal pulse and absence of foot pulse are tantamount
      to identifying the paramalleolar bypass graft candidate. Even the presence of
      palpable pedal pulses does not exclude patients who could achieve limb salvage
      with pedal bypass. That determination depends upon an angiogram. Pulsation and
      flow are not equivalent. Just as the obligations of the surgeon who performs an
      amputation are not discharged until healing and rehabilitation are complete,
      likewise, the vascular surgeon's duties after paramalleolar bypass must include a
      return to the ambulatory status. Careful follow-up, ongoing explicit patient and
      family education about foot care, and orthotics and shoes will enhance the life
      and life expectancy of the bipedal patient.

PMID- 7638717
TI  - Extra-anatomic reconstruction.
AB  - Extra-anatomic bypass grafts have proven to be effective in bypassing infected
      regions, in avoiding hostile abdomens, and in patients with limited life
      expectancy. The extra-anatomic bypass graft can be used as a temporizing conduit
      while infected fields are definitively treated. The recommendation to expand the
      role of extra-anatomic bypass grafts over more direct revascularization with an
      aortobifemoral artery bypass graft must be critically evaluated. With advances in
      anesthesia and critical care management, the postoperative mortality for
      aortobifemoral bypass is 3% to 5%, with an incidence of myocardial infarction of
      2%. Long-term primary patency of the aortofemoral bypass graft is 80% to 92% at 5
      years. The 5-year primary patency rate for the axillofemoral bypass graft of 50%
      to 73% does not strongly support the expanded role of extra-anatomic bypass in
      otherwise healthy patients undergoing aortoiliac bypass. Yet the extra-anatomic
      bypasses have a vital role in the management of selected patients and should be
      in the armamentarium of all vascular surgeons.

PMID- 7638718
TI  - The current status of prosthetic-vein composite grafts for lower extremity
      revascularization.
AB  - When infrageniculate lower extremity vascular reconstructions are required in the
      face of inadequate or insufficient autogenous vein, prosthetic-vein composite
      grafts remain a viable alternative. Graft patency and limb salvage for composite
      grafts are intermediate between those of completely autogenous and prosthetic
      bypasses alone. The sequential technique may offer superior patency in patients
      with the appropriate anatomy. The addition of adjunctive techniques such as a
      distal arteriovenous fistula and/or anticoagulation may further improve results.
      An algorithm illustrating the proper role of composite grafts for distal lower
      extremity reconstructions is shown in Figure 6. Any significant interval of
      patency is important in this group of patients in whom limb salvage can often be
      achieved by healing ischemic lesions and in whom overall life expectancy is
      limited.

PMID- 7638719
TI  - Operative adjuncts for distal revascularization.
AB  - The performance of distal arterial bypass procedures in poor outflow situations
      may require adjunctive techniques to maximize short- and long-term patency. The
      rationale and technique for the most commonly used modifications are presented
      along with the indications for use.

PMID- 7638720
TI  - Pharmacologic intervention to prevent graft failure.
AB  - Lower extremity vascular grafts, either vein or synthetic, fail for diverse
      reasons. Technical defects or poor surgical judgment doom a graft beyond any
      benefit pharmacotherapy can offer. Graft failure due to spontaneous thrombosis
      particularly affects prosthetic conduits, and use of antiplatelet agents
      (dextran, ASA) or anticoagulants (heparin, warfarin) is probably useful in this
      setting. An effective way to inhibit vein graft or anastomotic intimal
      hyperplasia remains elusive. Perhaps the most permanent and longstanding
      influence on lower extremity graft survival can be made through risk factor
      intervention aimed at arresting the progression of atherosclerosis. Aggressive
      treatment of hyperlipidemia, hypertension, smoking, and other known risk factors
      should be routinely and aggressively pursued in patients with lower extremity
      grafts, either autogenous or prosthetic. Lower extremity graft patency is
      optimally ensured by technically adept insertion of a proper autologous conduit
      in a well-selected patient. Pharmacotherapy may have a significant adjunctive
      role in the maintenance of graft patency, especially in high-risk settings such
      as limb salvage with associated poor outflow, a marginal vein graft, or the
      obligatory use of prosthetic material.

PMID- 7638721
TI  - Foot amputations.
AB  - When presented with an ischemic limb with forefoot necrosis of varying amounts,
      the surgeon often categorizes the need for amputation into toe, ray,
      transmetatarsal, below-knee, and above-knee. Adherence to this type of algorithm
      ensures a primary above- or below-knee amputation rate of 10% to 20%. The utility
      of the more uncommon amputations advocated here is an increase of limbs deemed
      eligible for revascularization and limb salvage. Furthermore, delaying the
      amputations until the vascular supply is normalized maximizes tissue salvage and
      minimizes prolonged hospitalizations with multiple amputations performed as a
      prelude to major amputation. Although these amputations are often looked upon as
      an afterthought by many vascular surgeons, careful execution here is as important
      to effective limb salvage as any distal bypass procedure.

PMID- 7638722
TI  - Management of infected aortic grafts.
AB  - Aortic graft infection will continue to occur in a small proportion of patients
      who undergo reconstructive aortic surgery. For most patients, the standard
      approach should use extra-anatomic bypass, followed by complete excision of the
      graft, as the treatment of choice. However, in selected patients who have
      localized infection, are high risk surgical candidates, or have grafts located in
      positions that preclude removal, less aggressive alternatives such as topical
      antibiotic irrigation, graft resection with debridement and replacement, and in
      situ replacement with a biologic graft take an increasing role. When prosthetic
      grafts are developed that are less susceptible to reinfection, owing to
      incorporation of antibiotics into the graft, in situ replacement may become the
      treatment of choice. In spite of many advances in the management of aortic graft
      infection, this complication continues to carry a high mortality and amputation
      rate, and consequently should be managed by surgeons who have a particular
      interest and experience in managing this particular problem. With a thorough
      understanding of the circumstances of the original operation, bacteria infecting
      the graft, extent of graft infection, and management alternatives, most patients
      can survive prosthetic aortic graft infections with a combined morbidity and
      mortality of less than 50%.

PMID- 7638723
TI  - Infections in lower extremity vascular grafts.
AB  - No set of rigid guidelines can replace a clinically rational and methodic
      approach to the patient with an infrainguinal graft infection. Some fundamental
      principles are common to infrainguinal graft infections that form the basis for
      selective management: 1. Graft preservation can be attempted when the graft is
      patent, the anastomosis is intact, and the patient is not septic. 2. Graft
      excision is mandatory when the patient presents with a thrombosed infected graft,
      anastomotic or graft hemorrhage, or significant systemic sepsis. 3. Graft
      preservation can be attempted in both vein and PTFE grafts but is not advised for
      Dacron grafts. This approach should be tempered by the extent and virulence of
      the underlying infection, especially when Pseudomonas aeruginosa is the
      pathologic organism. 4. Delayed hemorrhage and continued systemic sepsis
      represent early failures of graft preservation and mandate graft excision. 5.
      Revascularization may be accomplished through the infected bed, but it is
      generally prudent to proceed with extra-anatomic reconstruction utilizing
      alternative approaches to inflow and outflow vessels.

PMID- 7638724
TI  - Surgical research--facing new realities.

PMID- 7638725
TI  - Glucocorticoids mediate macrophage dysfunction in protein calorie malnutrition.
AB  - BACKGROUND: In hospitalized patients protein calorie malnutrition substantially
      increases the incidence of infection and death. Protein calorie malnutrition
      results in significant macrophage dysfunction. Whether a primary nutrient deficit
      or elevated glucocorticoids levels mediate this dysfunction is unclear. The aim
      of this study was to evaluate the neuroendocrine response to protein calorie
      malnutrition and its effects on macrophage function. METHODS: By use of a murine
      model of protein calorie malnutrition, mice were randomized to (1) a standard 24%
      casein diet (control), (2) protein-free diet (PFD), (3) PFD in adrenalectomized
      mice, (4) PFD plus the glucocorticoid receptor antagonist RU486 (10 mg/kg), or
      (5) a standard 24% casein diet plus a 50 mg corticosterone pellet implanted
      subcutaneously for 7 days. Mice were killed after 7 days, and body weight and
      serum albumin and corticosterone levels were measured. Peritoneal macrophages
      were obtained, and stimulated superoxide and interleukin-6 productions were
      measured. RESULTS: Protein calorie malnutrition significantly impaired macrophage
      function and elevated serum glucocorticoid levels. Blocking the stress
      corticosterone response with adrenalectomy or using RU486 to block corticosterone
      receptors prevented the impairment of macrophage function without restoring
      nutritional indexes (body weight and serum albumin level). Administration of
      glucocorticoids via a subcutaneous pellet reproduced macrophage impairment
      without leading to nutritional deficits. CONCLUSIONS: The neuroendocrine systemic
      response to protein calorie malnutrition with elevated serum corticosterone
      levels is a major determinant of macrophage dysfunction in protein calorie
      malnutrition.

PMID- 7638726
TI  - Regulation of inducible nitric oxide production by intracellular calcium.
AB  - BACKGROUND: Because increased nitric oxide (NO) production during sepsis can be
      detrimental to the host, inhibition of NO synthesis by various antagonists has
      been proposed as a therapeutic option. However, none of these approaches has
      addressed the possible regulation of inducible NO synthesis (iNOS) by endogenous
      intracellular signaling mechanisms. The purpose of our study was to determine
      whether intracellular calcium ([Ca2+]i) regulates iNOS. METHODS: The macrophage
      cell line RAW 264.7 cells stimulated to produce NO were cultured in the presence
      or absence of the calcium ionophore A23187, ionomycin, or the Ca(2+)-adenosine
      triphosphatase inhibitor thapsigargin. Supernatants and total cellular RNA were
      recovered for measurement of iNOS messenger RNA (Northern blot) and NO2- (stable
      end product of NO), respectively. Simultaneous measurement of [Ca2+]i was
      performed by fluorescence spectrophotometry. RESULTS: The calcium ionophore
      A23187, ionomycin, and thapsigargin all produced a dose-dependent inhibition of
      NO end product and iNOS messenger RNA (confirmed by densitometry) with a
      simultaneous increase in [Ca2+]i, confirmed by fluorescence spectrophotometry.
      This could not be reversed by exogenous L-arginine and was not observed if these
      agents were added beyond 0 hours of culture. CONCLUSIONS: Although iNOS is
      traditionally viewed as calcium independent, these data clearly show that [Ca2+]i
      regulates iNOS messenger RNA induction and end product synthesis. Endogenous
      cellular second messenger may thus be important in autoregulation of NO
      synthesis. Alternatives to pharmacologic or antagonist inhibition of NO deserve
      further investigation.

PMID- 7638727
TI  - Modulation of intestinal chloride secretion at basolateral transport sites:
      opposing effects of cyclic adenosine monophosphate and phorbol ester.
AB  - BACKGROUND: Although intestinal Cl secretion is largely regulated by apical Cl
      channels, we have shown that net secretory capacity can be controlled at a
      basolateral site, the Na-K-2Cl cotransporter (NKCC). Phorbol myristate acetate
      (PMA) was found to inhibit both cyclic adenosine monophosphate (cAMP)-regulated
      Cl secretion and basolateral NKCC function in parallel but not apical Cl
      channels. Because inhibition of NKCC function could occur by reducing the number
      of membrane NKCC units, we examined the effect of PMA on cAMP-regulated NKCC
      function and number. METHODS: NKCC function and number were assessed in the human
      intestinal line HT29cl.19A by bumetanide-sensitive uptake of rubidium 86 and by
      specific binding of 3H-bumetanide. RESULTS: The cAMP agonist forskolin enhanced
      bumetanide-sensitive 86Rb uptake and doubled the number of NKCCs. PMA decreased
      both basal and cAMP-stimulated uptake in time- and dose-dependent fashion. In
      addition, PMA down-regulated basal NKCC number and abolished cAMP-induced NKCC
      recruitment. CONCLUSIONS: PMA opposes the action of cAMP on NKCC function by
      reducing both basal numbers of NKCCs and cAMP-induced recruitment of NKCCs and
      not by reducing ion translocation per NKCC. These data further emphasize the
      potential for modulation of intestinal Cl secretion at basolateral sites.

PMID- 7638728
TI  - Fc gamma RII, Fc gamma RIII, and CD18 receptors mediate in part neutrophil
      activation on a plasma coated expanded polytetrafluoroethylene surface.
AB  - BACKGROUND: A biomaterial-induced polymorphonuclear neutrophil (PMN) defect may
      predispose the implanted vascular graft to infection. PMNs bind, activate, and
      undergo morphologic changes when exposed to uncoated or plasma coated expanded
      polytetrafluoroethylene (ePTFE) surfaces. The purpose of this study was to
      investigate whether the CD18 integrin receptor or the immunoglobulin receptors Fc
      gamma RII and Fc gamma RIII mediate either PMN binding or activation on ePTFE.
      METHODS: PMN binding and activation were determined after incubation of these
      cells on human immunoglobulin (IgG) or fibrinogen coated surfaces and uncoated or
      plasma coated ePTFE. PMN activation was measured by using the ferricytochrome
      reduction assay. Binding was determined with chromium 51-labeled PMNs. To block
      the Fc gamma RII, Fc gamma RIII, and CD18 receptors, PMNs were preincubated with
      the monoclonal antibodies (mAbs) IV.3, 3G8, and IB4, respectively. Irrelevant
      isotype matched mAbs were used as control. RESULTS: Monoclonal antibody IB4
      inhibited binding of activated PMNs to fibrinogen coated surfaces. Binding to IgG
      was affected by either mAb IB4 or IV.3, but the greatest degree of inhibition was
      achieved when mAbs IB4 and IV.3 were used in combination. IgG-induced activation
      was partially inhibited by mAb IV.3 but was fully inhibited by a combination of
      mAbs IB4 and IV.3 The mAbs did not affect PMN binding to uncoated or plasma
      coated ePTFE, nor was PMN activation on the uncoated ePTFE surface inhibited. PMN
      activation on the plasma coated ePTFE surface was, however, partially inhibited
      by the combination of mAb IB4 with either mAb IV.3 or 3G8. CONCLUSIONS: A
      synergistic interaction between the PMN Fc gamma RII receptor and the CD18
      integrin receptor accounts for surface bound IgG-induced cell activation. Both
      receptors also play a role in mediating PMN activation on the plasma-coated ePTFE
      surface.

PMID- 7638729
TI  - Neuroligands evoke calcium signaling in cultured myenteric neurons.
AB  - BACKGROUND: Myenteric neurons, which control gut motility and absorption, are
      heterogeneous in structure, electrophysiology, and neuropeptide content. We
      hypothesized that myenteric neurons would display heterogeneous responses to
      neuroligands found in enteric tissue. We examined increases in intracellular
      calcium ([Ca2+]i), an important second messenger, evoked by selected neuroligands
      in cultured myenteric neurons. METHODS: Primary cultures of guinea pig myenteric
      neurons were characterized by using a standard immunocytochemical stain for
      microtubule-associated protein (MAP2). Increases in [Ca2+]i were measured by
      digital imaging microscopy. Results expressed as mean +/- SEM, Student's t test.
      RESULTS: Cultured myenteric neurons examined with phase contrast and Nomarsky
      optics extend processes and stain positively with the neuron-selective stain
      MAP2. Histamine did not evoke calcium mobilization in cultured neurons, although
      progressive increases in [Ca2+]i were seen with bradykinin, glutamate, serotonin,
      cholecystokinin, bombesin, adenosine triphosphate (ATP), substance P, and
      acetylcholine. Enteric neurons differed from one another in the ability to
      respond to one, two, or three of the agonist combinations tested. Time in culture
      did not alter the percentage of neurons responding to ATP, substance P, or
      acetylcholine. ATP evoked equivalent [Ca2+]i increases in neurons examined at the
      three time points, whereas significant decrements in neuronal calcium
      mobilization were seen after 8 days in culture with substance P or acetylcholine
      (p < 0.05 versus 1 day in vitro). CONCLUSIONS: Cultured myenteric neurons extend
      processes and retain expression of neuron-specific antigens. Selected
      neuroligands found in enteric tissue increase [Ca2+]i, as a second messenger in
      subsets of myenteric neurons. Heterogeneity exists among cultured neurons in
      their ability to respond to ligand combinations. Changes in [Ca2+]i induced by
      neuroligands in myenteric neurons may be altered with time in vitro.

PMID- 7638730
TI  - Intercellular adhesion molecule-1 promotes neutrophil-mediated cytotoxicity.
AB  - BACKGROUND: Interaction of the CD11/CD18 complex on polymorphonuclear neutrophils
      (PMNs) and intercellular adhesion molecule (ICAM)-1 on endothelium is a critical
      event in PMN-mediated tissue injury. In addition, increased expression of ICAM-1
      on type I pneumocytes has been identified in a variety of pulmonary disorders
      associated with PMN-induced inflammation. We hypothesized that ICAM-1 up
      regulation is sufficient to promote cytotoxicity via activated PMNs. METHODS: The
      complementary DNA for human ICAM-1 was transfected into Chinese hamster ovarian
      (CHO) cells, which do not inherently express this adhesion receptor, by using the
      expression vector CD1.8. Fluorescence-activated cell sorter analysis revealed 62%
      CHO cell surface expression of ICAM-1. Wild type and transfected CHO cells were
      labeled with chromium 51 and exposed to quiescent or activated (1 mumol/L phorbol
      myristate acetate) PMNs for 4 hours. Subsets were pretreated with a monoclonal
      antibody to ICAM-1. PMN cytotoxicity was determined by specific percent 51Cr
      release. RESULTS: Incubation of quiescent PMNs with wild type and transfected CHO
      cells produced nominal cell lysis, 0.5% +/- 0.3% and 0.2% +/- 0.2%, respectively.
      Activated PMNs produced 13.6% +/- 3.2% versus 1.4% +/- 0.7% cell lysis, comparing
      transfected with wild type CHO cells, and 0.5% +/- 0.2% cell lysis after
      pretreatment with a monoclonal antibody to ICAM-1, p < 0.01. CONCLUSIONS: ICAM-1
      up-regulation is sufficient to promote cytotoxicity via activated PMNs. This may
      represent a potential target for attenuating PMN-mediated injury to endothelial
      and other cell lines, including parenchyma.

PMID- 7638731
TI  - Hypoxemia up-regulates interleukin-8 stimulated phagocytosis of polymorphonuclear
      leukocytes by differential regulation of CD32w and CD35 messenger RNA expression.
AB  - BACKGROUND: The purpose of these studies was to investigate the effect of
      hypoxemia on interleukin-8 (IL-8) regulation of phagocytosis and surface opsonic
      receptor expression of whole blood polymorphonuclear leukocytes (PMNs). METHODS:
      Whole blood PMNs were rendered hypoxemic (PvO2 less than 15 mm Hg) or normoxic
      (PvO2 equals 60 to 80 mm Hg) and incubated with IL-8 (50 ng/ml) before the
      sequential addition of serum-opsonized fluorescent microspheres (emission
      wavelength, 560 nm) and fluorescein isothiocyanate-conjugated mouse anti-human
      CD32w or CD35 antibodies (emission wavelength, 513 nm). Concomitant two color
      flow cytometric analysis was then performed to measure the mean channel
      fluorescence (MCF) and the percentage of positive PMNs. Steady-state messenger
      RNA levels for CD32w and CD35 were quantitated by means of Northern blot analysis
      by using total RNA extracted from purified PMNs from each study group. RESULTS:
      Hypoxemia increased IL-8 stimulated PMN phagocytosis (percentage of positive
      PMNs, 38 +/- 1.5 versus 27 +/- 2.0, MCF, 5491 +/- 182 versus 4060 +/- 121 for
      hypoxemia plus IL-8 versus normoxia plus IL-8, respectively; p < 0.05). Hypoxemia
      increased IL-8 stimulated PMN expression of CD32w and CD35 (MCF CD32w, 791 +/-
      105 versus 336 +/- 81; MCF CD35, 542 +/- 87 versus 254 +/- 41; p < 0.05). Under
      normoxic conditions IL-8 decreased messenger RNA levels for both CD32w and CD35,
      but under hypoxemic conditions IL-8 increased messenger RNA levels only for
      CD32w. CONCLUSIONS: Hypoxemia directly regulates IL-8 control of PMNs by
      increasing phagocytosis, receptor expression, and messenger RNA for these
      receptors. Studies investigating cytokine regulation of PMN function need to take
      into account oxygen tension when establishing the fundamental effects of
      cytokines on PMN physiology.

PMID- 7638732
TI  - In vivo gene therapy of a murine pancreas tumor with recombinant vaccinia virus
      encoding human interleukin-1 beta.
AB  - BACKGROUND: Recombinant vaccinia virus (VV) encoding human interleukin-1 beta
      (vMJ601hIL-1 beta) given intravenously persists in tumor tissue and expresses hIL
      1 beta for at least 9 days after treatment and is associated with significant
      retardation of tumor growth. To document the significance of this approach and to
      further elucidate the mechanism, this study compares the antitumor effect of
      vMJ601hIL-1 beta administered either intravenously or intratumorally and
      intravenous recombinant hIL-1 beta protein. METHODS: C57BL/6 mice with
      established subcutaneous pancreatic tumors were randomized to treatment with
      intravenous or intratumoral vMJ601hIL-1 beta, wild-type VV, saline solution, or
      intravenous recombinant hIL-1 beta protein in a blinded fashion. Toxicity and
      tumor size were measured. Data were analyzed with the Kruskal-Wallis and Wilcoxon
      tests. RESULTS: Treatment with intratumoral vMJ601hIL-1 beta repeatedly resulted
      in significant reduction in tumor size as compared with saline treated controls
      (p < 0.001). Tumor growth inhibition was consistently similar after intravenous
      or intratumoral vMJ601hIL-1 beta administration (p > 0.52). Wild-type VV given
      intratumorally or intravenously had no antitumor effect versus saline controls (p
      > 0.30). No significant toxicity or deaths resulted from vMJ601hIL-1 beta
      treatment. Recombinant hIL-1 beta protein administered intravenously caused
      severe toxicity (median lethal dose approximately 100 micrograms/kg), and no
      significant antitumor effect was observed at sublethal doses versus saline
      controls (p = 0.19). CONCLUSIONS: Direct, in vivo hIL-1 beta gene delivery and
      expression by recombinant VV given intravenously or intratumorally results in
      significant tumor growth inhibition, which appears to be a consequence of local,
      intratumoral vaccinia infection and production of hIL-1 beta.

PMID- 7638733
TI  - Allogeneic chimerism induces donor-specific tolerance to simultaneous islet
      allografts in nonobese diabetic mice.
AB  - BACKGROUND: Nonobese diabetic (NOD) mice develop a systemic autoimmune disease
      that resembles type I diabetes in human beings. Previous studies in NOD mice have
      shown that transplantation of bone marrow from normal donors to lethally
      conditioned recipients prevented the development of diabetes (B10.BR-->NOD,
      BALB/c-->NOD). The focus of the present study was to examine whether donor
      specific transplantation tolerance for islet allografts could be achieved if
      islet transplantations were performed coincident with the time of bone marrow
      infusion in diabetic NOD mice. Moreover, the transplanted islets were evaluated
      for evidence of recurrent autoimmunity. METHODS: Female NOD mice were followed
      until autoimmune diabetes occurred (urine glucose, to +; blood glucose level, 300
      mg/dl or greater). Diabetic NOD mice were irradiated with 950 cGy total body
      irradiation and received 30 x 10(6) untreated B10.BR bone marrow cells (B10.BR-
      >NOD). A simultaneous islet allograft was placed under the renal capsule within
      24 hours after infusion of the bone marrow cells. Mice were monitored by means of
      blood glucose levels, and histologic analyses were performed on the transplanted
      islet. RESULTS: Islet allografts genetically matched to the bone marrow donor
      were significantly prolonged (n = 5; mean survival time, 206 days or more) and
      showed no evidence for chronic rejection or recurrent insulitis, whereas major
      histocompatibility complex-disparate third-party allografts were rejected (n = 3;
      mean survival time, 37 days) and exhibited lymphocytic infiltration compatible
      with rejection on histologic evaluation. CONCLUSIONS: These data suggest that
      permanent donor-specific tolerance to islet allografts placed simultaneously with
      bone marrow transplantation can be achieved in diabetic NOD mice. Moreover,
      recurrent autoimmune destruction of the pancreatic tissue is prevented by the
      bone marrow chimerism.

PMID- 7638734
TI  - Mechanisms of gastric acid secretion in the fetal rabbit.
AB  - BACKGROUND: The parietal cell specific protein H+/K(+)-adenosine triphosphatase
      H+/K(+)-ATPase) is responsible for gastric acid secretion in adult mammals;
      however, its ontogeny and role in fetal acid secretion are unknown. The purpose
      of this study was twofold: (1) to determine the ontogeny of gastric acid
      secretion and parietal cell H+/K(+)-ATPase expression in the fetal rabbit and (2)
      to determine the role of H+K(+)-ATPase in fetal acid secretion. METHODS: For the
      ontogeny studies 88 fetuses from nine time-mated rabbits were studied at
      successive gestational ages. Gastric fluid and amniotic fluid pH were measured,
      and total gastric acid was determined by titration. Gastric microsomal protein
      was analyzed by Western blot analysis for H+/K(+)-ATPase expression by using a
      monoclonal antibody to the 94 kd alpha-catalytic subunit. To determine the role
      of H+/K(+)-ATPase in fetal acid secretion, 37 fetuses at day 26 from four time
      mated rabbits were treated with (1) omeprazole (20 mg/kg) injection into the
      amniotic sac (n = 13), (2) carrier injection (n = 12), or (3) no injection (n =
      12). Fetal gastric pH and titratable acid were measured at day 28. RESULTS:
      Amniotic fluid pH was neutral (7.44 to 7.64) throughout the third trimester.
      Gastric fluid pH was neutral (7.42 to 7.51) until day 25, when it decreased to
      7.16 +/- 0.23 (p < 0.05) and subsequently fell to 5.37 +/- 0.05 by day 30.
      Titratable gastric acid (micromoles) increased from 0 at day 20 to 54.7 +/- 5.4
      by day 30. By use of Western blot analysis and immunohistochemistry, gastric
      microsomal H+/K(+)-ATPase expression was absent from days 20 through 25 of
      gestation and first detectable at day 26, with qualitative increases to term.
      Omeprazole significantly inhibited pH (5.45 +/- 0.13 in controls, 5.56 +/- 0.12
      with carrier injection, and 6.01 +/- 0.10 with omeprazole injection; p < 0.05).
      CONCLUSIONS: These data suggest that (1) gastric acid acid secretion begins at
      day 25 of gestation and increases to term, (2) gastric microsomal H+/K(+)-ATPase
      expression is first detectable at day 26 of gestation, and (3) omeprazole
      inhibits, but does not abolish, gastric acid secretion in the fetal rabbit. We
      conclude that gastric acid secretion is present before birth in the fetal rabbit
      and is mediated, in part, by omeprazole-sensitive H+/K(+)-ATPase.

PMID- 7638735
TI  - Small bowel adaptation: counterregulatory effects of epidermal growth factor and
      somatostatin on the program of early gene expression.
AB  - BACKGROUND: Small intestinal crypt cell proliferation is essential to the normal
      renewal of the epithelium, as well as the adaptive responses that follow
      resection or injury. The present studies were designed to elucidate the molecular
      mechanisms by which epidermal growth factor (EGF) and somatostatin interact to
      regulate crypt cell proliferation. METHODS: Rat crypt (IEC-6) cells were
      maintained in Dulbecco's modified Eagle's medium plus 10% fetal calf serum and
      treated with EGF (10 or 100 ng/ml) or somatostatin (0.5 microgram/ml). Cell
      counts were done to examine the effects on cellular growth, and Northern blot
      analyses were carried out by using complementary DNA probes corresponding to
      various protooncogenes. RESULTS: EGF caused a 41% increase in cellular growth, an
      effect that was almost completely blocked by pretreatment (30 minutes) with
      somatostatin. EGF led to dramatic increases in c-fos (greater than 20-fold), c
      jun (2-fold), and jun B (3-fold) gene expression at 30 minutes, consistent with
      the previously characterized immediate-early gene response in IEC-6 cells.
      Somatostatin alone had no effects on protooncogene levels, but pretreatment with
      somatostatin resulted in a marked inhibition (80%, p < 0.001 in all cases) of the
      EGF-induced increases in protooncogene expression. CONCLUSIONS: Somatostatin
      inhibits the EGF-induced protooncogene expression in IEC-6 cells. The
      somatostatin inhibition of immediate-early gene expression lends support to its
      role as a negative growth regulator in intestinal epithelia and indicates that
      its effect occur at an upstream site in the cellular growth response.

PMID- 7638736
TI  - Alterations of the interleukin-4 pathway in production of tolerance by mixed
      hematopoietic chimerism.
AB  - BACKGROUND: The induction of specific tolerance could prevent acute and chronic
      rejection, as well as immunosuppressive complications, in recipients of
      vascularized organ allografts. Mixed hematopoietic chimerism is one approach to
      allogeneic tolerance. In these studies we examined whether mixed chimerism can
      confer tolerance to heart allografts across major and minor histocompatiblity
      barriers. We also examined the transcription of cytokine genes within the
      allografts of tolerance animals and in cell culture. METHODS: Adult Lewis rats
      were lethally irradiated and reconstituted with a mixture of 50 x 10(6) T-cell
      depleted bone marrow cells. Chimeric animals received heterotopic donor strain
      and third-party heart allografts and were assessed daily for rejection. Another
      set of chimeras received heart allografts that were examined at varying time
      points for transcription of cytokine genes by reverse-transcriptase polymerase
      chain reaction. RESULTS: Median graft survival in control animals was 6 days.
      Graft survival in 11 mixed chimeras ranged from more than 165 to more than 274
      days (p < 0.001), and no episode of rejection or graft-versus-host disease was
      observed. Examination of cytokine transcriptions revealed dramatic alterations in
      interleukin-4 transcription in vivo and in vitro. CONCLUSIONS: Alterations in
      cytokine gene transcription are descriptive of tolerance in this model. Mixed
      chimerism confers long-term unresponsiveness to heart allografts across major and
      minor histocompatibility barriers with desirable features for clinical
      application.

PMID- 7638737
TI  - Mechanisms of reprogrammed macrophage endotoxin signal transduction after
      lipopolysaccharide pretreatment.
AB  - BACKGROUND: Dysregulation of macrophage tumor necrosis factor (TNF) and
      interleukin-(IL-1) release results from repetitive lipopolysacharride (LPS)
      stimulation. In this study we investigated the mechanisms of LPS pretreatment
      (LPSp) signal transduction producing altered LPS-activated (LPSa) cytokine
      release. METHODS: Murine macrophages were treated with medium alone, actinomycin
      D, cycloheximide, a protein kinase C inhibitor (H7), or the nitric oxide synthase
      inhibitor L-NMA. Macrophages were then pretreated with 100 ng/ml LPSp and
      cultured in medium alone, a nitric oxide donor (sodium nitroprusside), or a
      cyclic adenosine monophosphate donor (8 bromoadenosine) for 20 hours. Cultures
      were then washed, and fresh medium containing 1 microgram/ml LPSa was added. TNF
      and IL-1 release in 24-hour supernatant was measured by bioassays. RESULTS: LPSp
      inhibited TNF and enhanced IL-1 release. The results with actinomycin D and
      cycloheximide suggested that LPSp effects did not require transcription, but IL-1
      enhancement required protein synthesis. Addition of 8-bromo-cyclic adenosine
      monophosphate, H7, or nitroprusside prevented LPSp-induced augmentation of IL-1
      but had no effect on inhibition of TNF release. Inhibition of LPSp-induced nitric
      oxide production with L-NMA had no effect on TNF or IL-1. CONCLUSIONS: Complex,
      independent, but incompletely understood signal transduction pathways for LPSp
      induced alterations in LPSa-stimulated macrophage TNF and IL-1 release were
      shown. Understanding altered signal transduction from prior LPS stimulation may
      suggest new therapies to control dysregulated macrophage cytokine release in
      sepsis.

PMID- 7638738
TI  - Y2 receptors decrease human pancreatic cancer growth and intracellular cyclic
      adenosine monophosphate levels.
AB  - BACKGROUND: Peptide YY (PYY), a 36 amino acid enteric hormone, is known to
      decrease pancreatic exocrine and endocrine function. Previous studies with BIM
      43004-1, a modified PYY(22-36) Y2 receptor agonist, have revealed diminished
      mitochondrial activity in pretreated pancreatic cancer cells in vitro. We
      investigated the effects of both PYY and BIM-43004-1 on pancreatic cancer growth
      in vivo. METHODS: The 100,000 to 150,000 human pancreatic cancer cells, Mia PaCa
      2, were orthotopically transplanted into 48 male athymic mice. After 1 week
      animals were treated with either PYY or BIM-43004-1 at 200 pmol/kg/hr via
      miniosmotic pumps for 2, 3, or 4 weeks. Paired controls received saline solution.
      At death tumor size and mass were measured. Receptor binding studies and
      intracellular cyclic adenosine monophosphate (cAMP) levels were measured in
      vitro. RESULTS: All mice had significant human cancer growth within the pancreas
      by histologic sections at 2, 3, and 4 weeks. Tumor mass was decreased by 60.5% in
      BIM-43004-1 treated mice and 27.1% in PYY treated mice. Receptor binding studies
      revealed binding of [125I]-BIM-43004-1 and displacement of ligand on competitive
      addition of nonradioactive BIM-43004-1. K dissociation constant of 4.5 nmol and
      27,000 receptors per cell were quantitated by receptor binding studies. In BIM
      43004-1 treated pancreatic cells a 52.5% decrease in intracellular cAMP levels
      was noted, whereas a 15.3% decrease was seen in PYY treated cells. CONCLUSIONS:
      BIM-43004-1, a novel Y2 synthetic agonist, specifically binds to human pancreatic
      cancer cells, decreases intracellular cAMP levels, and suppresses tumor growth in
      vivo. Adjuvant hormonal treatment with this Y2 receptor analog may be beneficial
      in the treatment of patients with pancreatic adenocarcinoma.

PMID- 7638739
TI  - Transfection of a murine fibrosarcoma with intercellular adhesion molecule-1
      enhances the response to adoptive immunotherapy.
AB  - BACKGROUND: Increasing the ability of antitumor effector cells to leave the
      vasculature and gain access to tumor cells may improve therapeutic efficacy. We
      undertook this study to determine whether increased expression of intercellular
      adhesion of molecular-1 (ICAM-1) by gene transfection would result in an improved
      response to adoptive immunotherapy in vivo. METHODS: C57BL/6 mice received 1 x
      10(6) tumor cells on day 0. Tumor cells examined were MCA-105 (parental), NeoR
      (MCA-105 transfected with the neomycin resistance gene), or Clones 81 or 149 (MCA
      105 cotransfected with NeoR and the gene for ICAM-1 and highly express ICAM-1).
      Animals were treated by use of no treatment, interleukin-2 alone (days 10 through
      14), hyperthermia alone (days 10 and 13), or interleukin-2 + hyperthermia, and
      tumor growth was reported as a ratio to size on day 10. In vitro cytotoxicity was
      assayed by using murine lymphokine-activated killer cells. RESULTS: Tumors
      transfected with ICAM-1 and treated with hyperthermia + immunotherapy grew
      significantly (p < 0.05) slower (mean, 0.78 +/- 0.16 on day 19) than parental
      tumor (size, 1.35 +/- 0.22) or tumor cells transfected with NeoR alone (1.21 +/-
      0.19). Tumors containing both MCA-105 and Clone 81 treated with hyperthermia +
      immunotherapy grew significantly slower (1.58 +/- 0.49 on day 19, p < 0.05) than
      untreated Clone 81 (2.38 +/- 0.46) or treated MCA-105 (2.49 +- 0.29) but more
      rapidly than treated Clone 81 (1.18 +/- 0.08), suggesting a paracrine efect for
      ICAM-1. CONCLUSIONS: These findings show that increased expression of ICAM-1 by
      tumor cells results in a significant increase in antitumor efficacy of combined
      interleukin-2 and hyperthermia in a murine model. Although the mechanism has yet
      to be elucidated, modulation of cellular adhesion may play a role in the
      therapeutic efficacy of cellular immunotherapy.

PMID- 7638740
TI  - Modulation of very late activation-2 laminin receptor function in breast cancer
      metastasis.
AB  - BACKGROUND: Very late activation-2 (VLA-2) is an integrin receptor for laminin
      that consists of an alpha 2- and a beta 1-subunit. In human breast cancer, down
      regulation of VLA-2 expression is related to positive nodal status. The
      functional significance of altered integrin expression in individual patients has
      never been investigated. To test the hypothesis that less adhesive primary breast
      cancer cells were predisposed to metastasize, variation in VLA-2 modulation of
      cell attachment to laminin with nodal status was studied. METHODS: Integrin
      expression was measured by means of immunohistochemistry on cryostat sections.
      Primary breast cancer cells were isolated by enzymatic disaggregation and
      immunomagnetic separation. Cell adhesion to laminin was evaluated in an in vitro
      assay, and the effect of monoclonal antibodies against the component subunits of
      VLA-2 was assessed. RESULTS: Adhesion of primary breast cancer cells from women
      with positive nodes to laminin was significantly reduced compared with women with
      negative nodes (p < 0.001, Wilcoxon signed rank test). VLA-2 antibodies inhibited
      primary breast cancer cell attachment of women with negative nodes but not women
      with positive nodes. Strong adhesion to laminin was related to node-negative
      status (chi-squared, 16.33; p < 0.001) and to positive integrin expression (chi
      squared, 31.54; p < 0.001). CONCLUSIONS: VLA-2-mediated adhesion of primary
      breast cancer cells to laminin differs with nodal status. Measurement of VLA-2
      expression may thus be of clinical value as a prognostic indicator in the
      assessment of breast cancer.

PMID- 7638741
TI  - Antitumor activity of three mouse mammary cancer cell lines after interferon
      gamma gene transfection.
AB  - BACKGROUND: The antitumor effects of three mouse mammary tumors transfected to
      express interferon-gamma were evaluated. METHODS: Three immunologically different
      tumors were used: DA3, EMT6, and 410. All three cell lines were successfully
      transfected with highly efficient viral vectors. Wild type or transfected tumor
      cells were injected subcutaneously into Balb/c mice. Animals were observed for
      tumor growth and the induction of immunologic memory. RESULTS: A significant
      decrease occurred in the size of all transfected tumors, EMT6 1.9 cm2, DA3 1.7,
      and 410 1.8 compared with nontransfected control tumors with a mean size of 4 cm2
      on day 30. To further test the development of immunity, animals were injected
      with either nontransfected or transfected tumors and challenged with
      nontransfected tumor. Animals immunized with transfected tumor cells had
      significantly smaller tumors, EMT6 2.5 cm2, DA3 3.1, and 410 2.4 compared with
      controls with a mean size of 4 cm2. No specific splenocyte cytotoxicity was
      shown. Expression of major histocompatibility complex class I antigens was
      enhanced in the 410 and DA3 tumor lines. CONCLUSIONS: Significant antitumor
      effects were observed after interferon-gamma gene transfection of three mouse
      mammary cancer cell lines. Up-regulation of major histocompatibility complex
      class I antigen expression is a partial explanation of these findings. These
      results provide preliminary studies for gene therapy of human breast cancer.

PMID- 7638742
TI  - Progress in genetic screening of multiple endocrine neoplasia type 2A: is
      calcitonin testing obsolete?
AB  - BACKGROUND: Recent identification of RET mutations in multiple endocrine
      neoplasia type 2A (MEN 2A) allows a DNA-based approach to diagnosis in lieu of
      calcitonin sampling. To prospectively evaluate the efficacy of mutational
      analysis, genetic screening was performed in 124 patients (53 male, 71 female;
      age, 1 month to 80 years) at risk for MEN 2A referred over 3 months. METHODS:
      Analysis used genomic DNA and a polymerase chain reaction-based denaturing
      gradient gel electrophoresis strategy for mutation detection at RET codons 609,
      611, 618, 620, and 634. Ninety-three of 124 patients were from established MEN 2A
      kindreds (group A), and screening replaced calcitonin testing. Twenty-one of 124
      patients (group B) represented index cases of medullary thyroid carcinoma (MTC),
      and DNA analysis was performed to distinguish sporadic from hereditary disease.
      Ten patients (group C) had modest calcitonin elevations or had undergone
      thyroidectomy without confirming pathologic results, and testing was undertaken
      to clarify status. RESULTS: Group A: RET mutations occurred in 29 (median age, 10
      years) of 93 patients, 14 of whom underwent thyroidectomy. No false-positive
      results were observed. Group B: five (24%) of 21 patients with seemingly sporadic
      MTC had RET mutations at codons 618 (one), 620 (one), or 634 (three). Group C:
      Nine of 10 patients with alleged MEN 2A had genetically negative results.
      CONCLUSIONS: Denaturing gradient gel electrophoresis reliably detects MEN 2A.
      Modest calcitonin elevations may lead to a false-positive diagnosis of MTC. DNA
      testing is the optimal approach to evaluating MEN 2A. Index cases of sporadic MTC
      should also undergo DNA analysis.

PMID- 7638743
TI  - Administration of anti-CD4 monoclonal antibody with intrathymic injection of
      alloantigen results in rat cardiac allograft tolerance.
AB  - BACKGROUND: We have previously reported the induction of donor-specific tolerance
      to cardiac allografts after intrathymic injection of alloantigen with
      simultaneous administration of antilymphocyte serum treatment to eliminate
      peripheral T cells. The present study determines whether prolongation of a fully
      major histocompatibility complex-mismatched cardiac allograft is achieved after a
      single administration of anti-CD4 monoclonal antibody (MoAb) combined with
      intrathymic injection of alloantigen. METHODS: Male Buffalo rats were given Lewis
      splenocytes via the intrathymic or intravenous route in combination with a single
      administration of anti-CD4 monoclonal antibody (OX-38) or anti-CD8 MoAb (OX-8) or
      both. Heterotopic cardiac transplantation was performed 21 days after intrathymic
      alloantigen or MoAb pretreatment or both. Fluorescence-activated cell sorter
      analysis determined changes in lymphocyte compartment T-cell subsets, and in
      vitro studies examined recipient cellular reactivity. RESULTS: By 21 days after
      anti-CD4 MoAb treatment earlier nonspecific immunosuppression had resolved with
      80% recovery of peripheral CD4+ T cells and restoration of recipient
      immunocompetence to allow normal rejection of a cardiac allograft. Combined
      treatment with intrathymic, but not intravenous, alloantigen plus anti-CD4 MoAb
      induced donor-specific tolerance to subsequent rat cardiac allografts. However,
      anti-CD8 MoAb combined with intrathymic alloantigen failed to induce tolerance
      despite a profound depletion of the CD8+ T-cell subset. CONCLUSIONS: Combined
      treatment of rats with intrathymic donor alloantigen and a single administration
      of anti-CD4, but not anti-CD8, MoAb significantly prolongs cardiac allograft
      survival across a fully major histocompatibility complex mismatched strain
      combination.

PMID- 7638744
TI  - Nitric oxide inhibition of endothelial cell mitogenesis and proliferation.
AB  - BACKGROUND: Endothelial cell (EC) proliferation is essential in vascular repair
      after injury to the vessel wall. Impaired EC proliferation may be an important
      factor contributing to vessel wall disease. Nitric oxide (NO) inhibits
      proliferation of many cells, including smooth muscle cells (SMC). We tested the
      hypothesis that NO inhibits EC proliferation and DNA synthesis. METHODS: Cultured
      canine venous ECs were treated with NO donors: S-nitroso-N-acetylpenicillamine
      (SNAP), S-nitroso-glutathione (GSNO), or spermine NONOate (SP NO). Proliferation
      was determined by cell counts after 48 hours. Parallel proliferation studies were
      done with rat aortic SMC. ECs synchronized in S phase were treated with the NO
      donor diethylamine NONOate (DEA NO), and DNA synthesis was measured as the
      incorporation of tritiated thymidine. A NO antagonist, cPTIO, was used to reverse
      the effects of DEA NO: RESULTS: Concentration-dependent (1 to 100 mmol/L)
      inhibition of EC proliferation (11% to 71% inhibition; p < 0.05) was seen with
      SNAP. Similar inhibition of proliferation was noted with the NO donors GSNO and
      SP NO and in SMC treated with SNAP. DEA NO caused concentration-dependent (0.1 to
      1 mmol/L) inhibition of EC DNA synthesis (39% to 85% inhibition; p < 0.05), which
      was reversed by cPTIO. CONCLUSIONS: NO inhibits proliferation and mitogenesis of
      cultured ECs. This may occur in certain pathologic states, where production of NO
      in plaques and diseased vessels impedes reendothelialization, thus contributing
      to adverse thrombotic and vasospastic events.

PMID- 7638745
TI  - Selective stimulation of endothelial cell proliferation with inhibition of smooth
      muscle cell proliferation by fibroblast growth factor-1 plus heparin delivered
      from fibrin glue suspensions.
AB  - BACKGROUND: Pretreatment of expanded polytetrafluoroethylene grafts with fibrin
      glue (FG) containing fibroblast growth factor-1 (FGF-1) (10 ng/ml) and heparin
      (50 units/ml) has been shown to induce a transmural angiogenesis with
      proliferation of both endothelial cells (ECs) and smooth muscle cells (SMCs) in
      dogs. To induce EC without SMC proliferation, we studied the effects of different
      FGF-1:heparin ratios within FG in vitro. METHODS: First passage human umbilical
      vein ECs (factor VIII+) or primary canine carotid artery SMCs (alpha-actin +)
      were seeded onto 96-well plates coated with FG containing 10 ng/ml FGF-1 and 0,
      5, 50, or 500 units/ml heparin. Control wells were coated with FG without FGF-1
      or heparin. Cells were fed standard growth medium without soluble FGF-1 or
      heparin. Tritiated thymidine (1 microCi/well) was added after 1, 2, or 3 days,
      and proliferation was assayed by scintillation counting 48 hours later. RESULTS:
      For both ECs and SMCs, proliferation on FG containing FGF-1 but no heparin was
      not different from control. EC proliferation on FG containing FGF-1 was
      significantly increased by addition of 5, 50, or 500 units/ml heparin (+68%,
      +99%, and +106%, respectively; p (0.0001 for all), reflecting the synergism of
      FGF-1 by heparin. SMC proliferation was also significantly increased by the
      addition of 5 or 50 units/ml heparin (+85% and +66%, respectively; p (0.0001 for
      both). However, SMC proliferation with 500 units/ml heparin was significantly
      decreased from control (-12%; p = 0.014), reflecting heparin's SMC growth
      inhibitory activity. CONCLUSIONS: FG containing 10 ng/ml FGF-1 and 500 units/ml
      heparin stimulates EC proliferation while inhibiting SMC proliferation in vitro.
      Application of this modified FG to vascular grafts or to arteries after direct or
      transcutaneous interventions may promote endothelialization without intimal
      hyperplasia.

PMID- 7638746
TI  - An educational intervention in the surgical intensive care unit to improve
      ethical decisions.
AB  - BACKGROUND: The objective of this study was to determine whether an educational
      intervention on medical ethics offered during a surgical intensive care unit
      (SICU) rotation could effect meaningful change in a tertiary SICU. METHODS: A
      case-based education program was presented weekly to the surgical residents
      during their SICU rotation. Cases for study were designed to deal with specific
      ethical issues common to the SICU. Cases were studied with the residents in a
      group facilitated by a SICU attending physician and a nursing director. The
      effect of the course was monitored by case review and by the length of stay (LOS)
      assessment for patients who died in the SICU during 1990, the base year, through
      1993. RESULTS: Discussions of an ethical nature occurred more regularly and
      earlier during these 4 years as determined by case reviews. For patients who died
      after being in the SICU a minimum of more than 30 days, a marked decrease
      occurred in the SICU LOS from 27.8 +/- 3.7 days in 1990 to 15.7 +/- 2.4 days in
      1993 (p < 0.05). The number of deaths per year and the average acuity measured by
      the diagnosis related group score were similar during the 4 years. The LOS in the
      hospital for dying patients from non-SICU services remained similar during the
      same time frame. These changes resulted in the dying patients using 1003 SICU
      days in 1993, down from the 2028 days used in 1990 (p < 0.05). CONCLUSIONS: We
      conclude that through offering a clinical ethics program during the SICU portion
      of the residency training, residents increased knowledge and skill in addressing
      and integrating practical ethical issues into their surgical resident practice.
      In addition, patient care directly improved with an associated reduced SICU LOS
      and reduced cost.

PMID- 7638747
TI  - Variability in the clinical skills of residents entering training programs in
      surgery.
AB  - BACKGROUND: Residents may have significant differences in clinical skills at the
      start of their surgical training. The purpose of this study was to investigate
      the variability in these skills by using an objective structured clinical
      examination. METHODS: A needs assessment was performed, and an objective
      structured clinical examination composed of 10, two-part stations was developed.
      Standardized patients (SPs) were trained, validated, and used as both simulated
      patients and evaluators to assess history taking, physical examination, and
      interpersonal skills of 10 first-year surgical residents. Structured patient
      notes (PNs) written by residents after the SP encounters were used to assess
      history and physical examination documentation skills. Data from one station were
      not used because more than 25% of the SP ratings were missing. RESULTS: The alpha
      reliability was 0.78 for SP ratings, 0.91 for PN scores, and 0.91 for the
      combined scores. ANOVA revealed significant variation in individual residents'
      clinical skills as assessed by SPs (F = 4.56, p < 0.01), PNs (F = 11.09, p <
      0.001), or both (F = 10.9, p < 0.001). Paired t tests showed that residents
      scored significantly higher on history taking than on physical examination and
      attained significantly lower scores on documentation as compared with performance
      of both history and physical examination (p < 0.001 for each comparison).
      CONCLUSIONS: The results showed significant variability in clinical skills of the
      group of residents and yielded detailed information on the performance of each
      resident. The data were shared with individual residents and are being used to
      make changes in the educational activities of the program.

PMID- 7638748
TI  - Peptide derivatives of three distinct lipopolysaccharide binding proteins inhibit
      lipopolysaccharide-induced tumor necrosis factor-alpha secretion in vitro.
AB  - BACKGROUND: Bactericidal permeability increasing protein (BPI), Limulus anti
      lipopolysaccharide factor (LALF), and lipopolysaccharide binding protein (LBP)
      are three distinct proteins that bind to lipopolysaccharide (LPS). Intriguingly,
      binding of BPI and LALF to LPS results in neutralization of LPS activity, whereas
      the binding of LBP to LPS creates a complex that results in augmentation of LPS
      activity. Despite their different effector functions, we hypothesized that
      peptides based on the sequences of the proposed LPS-binding motif from each
      protein would neutralize LPS in vitro. METHODS: Three peptide sequences, each 27
      amino acids in length, of the proposed LPS-binding motif of BPI (BG38), LALF
      (BG42), and LBP (BG43) were synthesized. These peptides were then tested for
      their: (1) ability to inhibit macrophage secretion of TNF-alpha after stimulation
      by LPS derived from Escherichia coli, Klebsiella pneumoniae, Pseudomonas
      aeruginosa, and Serratia marcescens; and (2) bactericidal activity against these
      same four gram-negative bacteria in vitro. RESULTS: Synthetic peptides BG38 (BPI
      derived), BG42 (LALF-derived), and BG43 (LBP-derived) but not control peptide
      significantly inhibited LPS-induced tumor necrosis factor-alpha secretion by
      macrophages and mediated the lysis of gram-negative bacteria in vitro. In
      addition, preincubation of LPS with peptide BG38 mediated complete protection
      subsequent to lethal endotoxin challenge. CONCLUSIONS: These data demonstrate
      that small peptides derived from BPI, LALF, and LBP retained significant
      endotoxin-neutralizing and bactericidal activity against many different gram
      negative bacteria in vitro. Identification of this conserved LPS-binding region
      within each protein may aid in the development of new immunomodulatory reagents
      for use as adjuvant therapy in the treatment of gram-negative bacterial sepsis.

PMID- 7638749
TI  - Molecular regulation of lung endothelial glutamine synthetase expression.
AB  - BACKGROUND: The lungs play a crucial role in maintaining amino acid homeostasis
      by exporting glutamine. Lung glutamine release is increased markedly in patients
      with sepsis, and in rat models injection of endotoxin causes up-regulation of
      glutamine synthetase (GS), the principal enzyme of glutamine synthesis. To
      investigate the molecular regulation of this response in the lung
      microvasculature we studied the effects of several hormones and cytokines that
      mediate the septic response on the expression of GS in rat microvascular
      pulmonary endothelial cells (MPECs). METHODS: MPECs were grown to confluence and
      incubated with the synthetic glucocorticoid dexamethasone, prostaglandins,
      cytokines, or activated complement C5a. Cellular lysates were prepared and total
      cellular RNA was extracted, hybridized with a GS complementary DNA derived probe,
      and normalized to reduced glyceraldehyde-phosphate dehydrogenase. GS protein
      content was determined by Western blotting with a GS antibody. RESULTS: Of the
      compounds tested, only dexamethasone caused a marked increase (tenfold or
      greater) of GS messenger RNA and protein levels in MPECs. Dexamethasone-induced
      accumulation of GS messenger RNA was rapid, dose-dependent, and maximal after 4
      hours of exposure. GS protein levels were maximal after 8 hours and remained
      elevated for at least 48 hours. The dose of dexamethasone sufficient to induce
      50% of maximal GS messenger RNA and protein level increase was approximately 10
      nmol/L. The dexamethasone-induce increase of GS messenger RNA level was
      completely blocked by the glucocorticoid receptor antagonist RU38486 and by the
      transcriptional inhibitor actinomycin D but was not inhibited by the
      translational inhibitor cycloheximide. CONCLUSIONS: Glucocorticoids augment GS
      expression in rat lung microvascular endothelial cells in a manner consistent
      with a direct transcriptional response via glucocorticoid receptors. Other septic
      response mediators had minimal effect on GS expression. Induction of GS
      expression by adrenocorticoids is likely to contribute to the marked ability of
      the lungs to augment glutamine production during septic states.

PMID- 7638751
TI  - Intestinal epithelial cells down-regulate macrophage tumor necrosis factor-alpha
      secretion: a mechanism for immune homeostasis in the gut-associated lymphoid
      tissue.
AB  - BACKGROUND: The gut lumen contains more than 10(6) organisms per gram of luminal
      contents. The mechanisms that limit the response of macrophages in the lamina
      propria to these microbial antigens are unknown, although an intrinsic defect in
      this mechanism may contribute to the development of inflammatory bowel disease.
      Intestinal epithelial cells (IEC) may play an important role in mediating tonic
      down-regulation of local immune cell activation. The purpose of this study was to
      discern whether IEC might modulate macrophage activation in response to a variety
      of microbial stimuli. METHODS: Thioglycollate-elicited murine peritoneal
      macrophages were activated by endotoxin, zymosan, Escherichia coli, and Candida
      albicans in the presence or absence of IEC from the rat intestinal epithelial
      cell line IEC-6. Macrophage tumor necrosis factor-alpha (TNF-alpha) secretion was
      determined by enzyme-linked immunosorbent assay. RESULTS: Lipopolysaccharide or
      zymosan-activated macrophages in coculture with IEC secreted significantly less
      TNF-alpha than macrophages cultured alone. The inhibitory effect of the IEC was
      dependent on their activation by lipopolysaccharide. Interleukin-1 alpha
      production was not affected. IEC-mediated suppression of macrophage TNF-alpha
      secretion was reversed by indomethacin but not by neutralizing antibody to TGF
      beta. CONCLUSIONS: Lipopolysaccharide-activated IEC down-regulate macrophage TNF
      alpha secretion in response to microbial stimuli through a prostanoid-mediated
      mechanism. IEC may mediate tonic down-regulation of immune cell activation in the
      gut-associated lymphoid tissue and may thereby regulate local and systemic
      inflammatory responses.

PMID- 7638750
TI  - Sepsis and endotoxemia stimulate intestinal interleukin-6 production.
AB  - BACKGROUND: Endotoxemia stimulates tumor necrosis factor (TNF) and interleukin-1
      (IL-1) production in mucosa of the small intestine, but the effect on IL-6
      production is not known. Intestinal IL-6 may be especially important, considering
      its role in the acute phase response. We tested the influence of endotoxemia and
      sepsis in mice on intestinal IL-6 and IL-6 messenger RNA (mRNA) levels. METHODS:
      Mice were injected with lipopolysaccharide (LPS 10 mg/kg) or saline solution. In
      some experiments animals were pretreated with indomethacin (5 mg/kg) or N-nitro-L
      arginine (NNA, 100 mg/kg) before LPS injection. In other experiments, sepsis was
      induced by cecal ligation and puncture (CLP); controls were sham operated. Serum
      and jejunal mucosa were harvested at intervals during 16 hours, and IL-6 levels
      were determined by enzyme-linked immunosorbent assay. IL-6 mRNA was detected by
      polymerase chain reaction. RESULTS: Endotoxemia and sepsis increased serum and
      mucosal IL-6 and IL-6 mRNA, with maximum levels noted at 1 and 4 hours after LPS
      and at 8 hours after CLP. Pretreatment of endotoxemic mice with indomethacin or
      NNA blunted the increase in mucosal IL-6. CONCLUSIONS: Results suggest that
      sepsis and endotoxemia stimulate IL-6 production in small intestinal mucosa and
      that this response may be transcriptionally regulated. The effect of endotoxemia
      may be partly mediated by prostaglandins and nitric oxide. The results also
      suggest that the intestinal mucosa may be a participant in the cytokine response,
      rather than just a passive bystander.

PMID- 7638752
TI  - Glutamine-mediated regulation of heat shock protein expression in intestinal
      cells.
AB  - BACKGROUND: Glutamine is crucial in the growth and protection of intestinal
      mucosa; the molecular mechanisms for these effects are not known. Heat shock
      proteins (hsp) are stress-responsive genes that protect cells from various
      injuries. The purpose of this study was to determine whether glutamine alters hsp
      expression in intestinal cells after injury. METHODS: IEC-6 (rat intestinal
      crypt) cells were grown to 80% confluence, rinsed free of medium and serum, and
      then grown in medium containing various concentrations of L-glutamine (0.5 to 8.0
      mmol/L) for 24 hours. Cells were then exposed to heat shock (43 degrees C for 1
      hour) and RNA and protein were extracted at 0, 2, 8, and 24 hours after heat
      shock. Northern hybridizations were performed using an hsp 70 complementary DNA.
      Western blots were performed by using antibodies specific to the inducible and
      constitutive forms of hsp70. RESULTS: Northern blot analysis demonstrated a
      fourfold stimulation of hsp70 messenger RNA 2 hours after heat shock in IEC-6
      cells supplemented with 8.0 mmol/L glutamine compared with 0.5 and 1.0 mmol/L
      glutamine. In addition, inducible Hsp70 protein levels were increased threefold
      in IEC-6 cells given glutamine (8.0 mmol/L) at 24 hours after heat shock.
      CONCLUSIONS: Glutamine augments hsp70 messenger RNA and protein expression in gut
      derived IEC-6 cells after injury. Our findings demonstrate a novel mechanism for
      the enhanced cytoprotection of gut mucosa conferred by administration of
      glutamine and suggest that supplemental glutamine may be required after injury to
      enhance expression of stress-responsive genes in the gut.

PMID- 7638753
TI  - Postinjury neutrophil priming and activation: an early vulnerable window.
AB  - BACKGROUND: Generation of extracellular, cytotoxic superoxide anion (O2-) by
      polymorphonuclear neutrophils (PMNs) contributes to an unbridled inflammatory
      response that can precipitate multiple organ failure (MOF). Release of O2- is
      markedly enhanced when activated PMNs have been previously "primed" by
      inflammatory mediators, such as those expressed after trauma. We therefore
      hypothesized that PMN priming occurs as an integral part of the early
      inflammatory response to trauma. METHODS: PMNs were obtained from 17 high-risk
      patients with torso trauma at 3, 6, 12, 24, 48, and 72 hours after injury, as
      well as from 10 healthy donors, and the in vitro release of O2- was quantitated
      with a kinetic, superoxide dismutase (SOD)-inhibitable cytochrome c reduction
      assay. PMN O2- release was measured in the presence and absence of 1 mumol/L N
      formyl-methionyl-leucyl-phenylalanine (fMLP) and after priming and activation
      with 20 nmol/L platelet-activating factor (PAF) and 1 mumol/L fMLP, respectively.
      RESULTS: In vitro PMN O2- release was used to determine whether postinjury PMNs
      were (1) activated in vivo, (2) primed in vivo, or (3) primable in vitro.
      Unstimulated PMNs from trauma patients spontaneously expressed modest amounts of
      O2- in vitro from 6 to 48 hours after injury, suggesting endogenous activation.
      Also, fMLP-activated PMNs collected between 3 and 24 hours after injury expressed
      more O2- than controls (p < or = 0.02), indicating in vivo, trauma-related
      priming. Furthermore, postinjury PMNs were maximally primed in vivo (i.e., in
      vitro exposure to PAF before fMLP activation failed to significantly enhance O2-
      release) as compared to PMNs treated with fMLP. CONCLUSIONS: These data indicate
      that major torso trauma (first hit) primes and activates PMNs within 3 to 6 hours
      after injury. Consequently, we postulate that postinjury priming of PMNs may
      create an early vulnerable window during which a second hit (e.g., a secondary
      operation or delayed hemorrhage) activates exuberant PMN O2- release, rendering
      the injured patient at high risk for MOF.

PMID- 7638754
TI  - Inhibitory activity of intestinal intraepithelial lymphocytes.
AB  - BACKGROUND: Intestinal intraepithelial lymphocytes (iIEL) are the first line of
      lymphoid cells exposed to orally absorbed foreign antigen. Because of this unique
      position, we hypothesized that the iIEL down-regulates the immune response to
      foreign antigen to prevent broad sensitization. METHODS: One-way mixed lymphocyte
      cultures (MLCs) were performed with Brown Norway (BN) as the responder and
      irradiated Lewis rats as the stimulator. BN iIEL or control cells (irradiated BN
      spleen-thymus cells) were added to the MLCs to assess their inhibitory function.
      RESULTS: When iIEL cells comprised 0.63% of well volumes, a significant (p <
      0.05) decline in MLC proliferation was seen. To determine whether this inhibitory
      action was mediated by a soluble factor, supernatant from iIEL cultured with
      irradiated Lewis spleen-thymus cells was added to MLCs and was compared with the
      addition of culture medium as the control group. The iIEL group proliferated
      significantly less (p < 0.05) than the control group. To further define the
      mechanism of action, iIEL-conditioned supernatant was treated with neutralizing
      antibody to transforming growth factor-beta (25 micrograms/ml) or control
      immunoglobulin. Treated supernatant was then added to an MLC, resulting in a
      partial loss of inhibitory action. CONCLUSIONS: The iIEL appears to significantly
      suppress a response to allogeneic stimuli via a mechanism mediated by the action
      of one or more soluble factors. Transforming growth factor-beta may well be one
      of the mediators of this inhibitory action.

PMID- 7638755
TI  - Efficacy of inhaled cyclosporine in lung transplant recipients with refractory
      rejection: correlation of intragraft cytokine gene expression with pulmonary
      function and histologic characteristics.
AB  - BACKGROUND: Refractory rejection is a major cause of morbidity and death among
      lung transplant recipients. Traditional rescue therapies have proved only
      modestly successful. We recently demonstrated the safety of inhaled cyclosporine
      for patients with end-stage chronic rejection; this trial was extended to
      patients with refractory acute rejection. The present study was to determine
      whether effective inhaled cyclosporine therapy was correlated with suppression of
      cytokine gene expression. METHODS: Twelve lung transplant recipients were
      studied. Maintenance therapy, cyclosporine or FK 506, azathioprine, and
      prednisone, was continued, and inhaled cyclosporine at a dose of 300 mg/day was
      added. Pulmonary function testing and histologic characteristics from
      transbronchial biopsy specimens were used to assess efficacy of therapy.
      Bronchoalveolar lavage (BAL) and peripheral blood cells were analyzed for the
      presence of messenger RNA by using 32P-labeled primers of cytokines interleukin-2
      (IL-2), IL-6, IL-10, and interferon-gamma (gamma) via reverse transcriptase
      polymerase chain reaction. RESULTS: Nine of 12 patients (five with acute
      rejection, four with chronic rejection) exhibited histologic resolution of
      rejection within 3 months of inhaled cyclosporine therapy. Pulmonary function
      (forced expiratory volume in 1 second) improved from pretherapy levels in the
      patients with acute rejection (p < 0.05). All of the nine histologic responders
      exhibited 4- to 150-fold decreases (p < 0.05) in IL-6 and interferon-gamma
      messenger RNA levels in the BAL, whereas the three patients who failed exhibited
      persistent or increased cytokine profiles. IL-2 and IL-10 in BAL and peripheral
      blood lymphocyte cytokines were not informative. CONCLUSIONS: These results
      indicate that inhaled cyclosporine is effective therapy for refractory pulmonary
      rejection and that its mechanism of action is associated with suppression of
      proinflammatory cytokines IL-6 and interferon-gamma within the allograft.

PMID- 7638756
TI  - Inclusion of peripancreatic lymph node cells prevents recurrent autoimmune
      destruction of islet transplants: evidence of donor chimerism.
AB  - BACKGROUND: Recurrent autoimmune beta-cell destruction may contribute to the poor
      results of clinical islet transplantation. Pancreas transplants from diabetes
      resistant BB rats (BB-DR) are uniformly successful in autoimmune diabetic BB rats
      (BB-Ac), but isolated islets are destroyed, despite immunosuppression. In this
      study we tested the hypothesis that whole pancreas transplants abrogate
      autoimmunity by passive transfer to the host of an autoregulatory T-cell subset.
      METHODS: BB-Ac rats served as recipients of BB-DR or Wistar Furth (WF) pancreas
      or islet transplants. Two cohorts of islet transplants included 50 or 100 x 10(6)
      peripancreatic lymph node cells (LNCs). Recipients were monitored for recurrent
      diabetes and subjected to fluorescence-activated cell sorter analysis of
      peripheral blood lymphocytes after 200 days by using monoclonal antibodies to
      class I, CD4, CD8, RT6.2, and RT6.1. RESULTS: BB-DR pancreas transplants replete
      the RT6.1+ T-cell subset in BB-Ac rats, whereas BB-DR islet transplants, which
      are susceptible to recurrent autoimmunity, do not. Addition of 100 x 10(6) LNC
      results in repletion of RT6.1 to the same degree as the whole pancreas and leads
      to complete protection of the islets. WF pancreas transplants result in the
      appearance of RT6.2+ T cells in BB-Ac recipients, an RT allele that BB rats lack.
      CONCLUSIONS: BB-Ac rat recipients of whole pancreatic or islets plus LNCs
      transplants become chimeric for a donor T-cell population that prevents recurrent
      autoimmune diabetes. Deliberate inclusion of donor lymphoid cells with clinical
      islet transplants may be beneficial.

PMID- 7638757
TI  - Interferon-gamma and interleukin-10 messenger RNA are up-regulated after
      orthotopic liver transplantation in tolerant rats: evidence for cytokine-mediated
      immune dysregulation.
AB  - BACKGROUND: Immune regulation requires antigen recognition, signaling,
      activation, secretion of cytokines, and effector function by lymphocytes.
      Although there is redundancy in the activation and function of the immune
      response, some cytokines simultaneously promote and suppress different pathways
      of immunity. In the experiments reported here we compare cytokine gene expression
      within liver allografts from tolerant rats with normal and isografted liver
      tissue. We also compare the secretion of interferon-gamma (IFN-gamma) in the
      supernatant from mixed lymphocyte cultures by using peripheral blood lymphocytes
      stimulated against donor antigen. METHODS: Orthotopic liver transplantations were
      performed using the cuff technique without hepatic artery revascularization.
      Nonisotopic in situ hybridization (ISH) was used to detect and localize messenger
      RNA to specific cells within tissue. Antisense DNA probes were generated to
      interleukin-2 (IL-2), IL-4, IL-10, and IFN-gamma. One-way mixed lymphocyte
      cultures were set up against irradiated donor splenocytes, and the supernatant
      was collected to measure IFN-gamma by enzyme-linked immunosorbent assay. RESULTS:
      Expression of IFN-gamma and IL-10 was up-regulated in tolerant animals versus
      normal or isografted liver (p = 0.0002 and 0.0001, IFN-gamma and IL-10,
      respectively). In situ hybridization localized the expression of messenger RNA
      predominantly to the cytoplasm of the hepatocytes. Levels of IFN-gamma were
      higher in the supernatant from proliferating peripheral lymphocytes against donor
      antigen from tolerant animals versus naive control animals. CONCLUSIONS:
      Expression of IFN-gamma and IL-10 is up-regulated in hepatocytes from allograft
      tissue after orthotopic liver transplantation. We believe that the up-regulation
      of IL-10 cross-regulates the effector function of IFN-gamma and supports cytokine
      mediated immune dysregulation, which may be a mechanism of tolerance after
      orthotopic liver transplantation in rats.

PMID- 7638758
TI  - Influence of hypercortisolemia on soluble tumor necrosis factor receptor II and
      interleukin-1 receptor antagonist responses to endotoxin in human beings.
AB  - BACKGROUND: We have previously reported that the antecedent administration of
      glucocorticoids altered both the hormonal and proinflammatory cytokine responses
      to lipopolysaccharide (LPS) when administered to human volunteers. In that study,
      subjects with vastly exaggerated levels of tumor necrosis factor (TNF) and
      interleukin (IL)-6 12 and 144 hours after cortisol infusion exhibited hemodynamic
      and hormonal responses no different from those of untreated subjects after
      endotoxin. The current study examined levels of the antiinflammatory cytokines
      interleukin-1 receptor antagonist (IL-1ra) and soluble receptors to tumor
      necrosis factor (sTNF-R) in the same setting of the previous report. METHODS:
      Hydrocortisone succinate was infused into healthy volunteers. LPS was then
      injected immediately or was delayed by 6, 12, or 144 hours (C, C-6, C-12, and C
      144, respectively). Subjects receiving LPS alone served as controls. Plasma was
      analyzed to determine levels of TNF, sTNF-R and IL-1ra by enzyme-linked
      immunosorbent assay before administration of LPS and at 30-minute intervals after
      administration of LPS for 6 hours. RESULTS: Levels of sTNF-R increased after LPS
      administration in all groups (p < 0.05 versus baseline) with a significantly
      higher level recorded in the subjects having received hydrocortisone 144 hours
      before (C-144, p < 0.05 versus all other groups). TNF levels remained
      undetectable in association with immediate infusion of LPS (C) and the relatively
      short delay group (C6). This cytokine peaked 90 minutes after LPS in all other
      groups, with a significantly higher peak in the C-144 subjects when compared with
      controls. IL-1ra levels rose in all groups but to a lesser extent in the C group
      (p < 0.05). CONCLUSIONS: These data confirm that glucocorticoids influence the
      production of both sTNF-R and IL-1ra. The potential for an exaggerated response
      of sTNF-R exists for an extended period of time after exposure to
      glucocorticoids.

PMID- 7638759
TI  - Antioxidants attenuate endotoxin-induced activation of alveolar macrophages.
AB  - BACKGROUND: Endotoxin (lipopolysaccharide [LPS]) stimulation of tissue-fixed
      macrophages induces the generation of toxic oxidants. However, recent studies
      also implicate redox changes in both the signal transduction pathways for
      cytokine genes and the generation of physiologically active arachidonic acid
      metabolites. Because cytokines and arachidonic acid metabolites initiate and
      perpetuate deleterious systemic inflammatory responses, we tested whether
      macrophage activation could be modulated by antioxidants. METHODS: Rabbit
      alveolar macrophages were obtained by bronchoalveolar lavage, isolated, treated
      with the antioxidants vitamin E or N-acetylcysteine (NAC), and stimulated with an
      optimal dose of LPS (10 ng/ml). Assays were performed for tumor necrosis factor
      (TNF), procoagulant activity, and prostaglandin E2. Total cellular RNA was
      extracted for Northern blot analysis of TNF messenger RNA. RESULTS: Exposure of
      the macrophage to the antioxidants vitamin E and NAC inhibited TNF production,
      accumulation of TNF messenger RNA, procoagulant activity expression, and
      prostaglandin E2 production. CONCLUSIONS: Macrophage signal transduction of LPS
      is dependent on the generation of reactive oxygen intermediates that can be
      blocked both at the level of the lipid membrane (vitamin E) and at the
      intracellular level (NAC). This suggests a potential therapeutic role for
      antioxidants is disease states such as adult respiratory distress syndrome and
      multiple organ failure syndrome, which are characterized by excessive macrophage
      activation.

PMID- 7638760
TI  - Early, complete burn wound excision partially restores cytotoxic T lymphocyte
      function.
AB  - BACKGROUND: Cytotoxic lymphocytes (CTLs) are an important component of immune
      function, involved in antigen recognition and resistance to viral infection. Burn
      injury suppresses cell-mediated immunity, induces allograft tolerance, and
      increases the risk of viral infection, but the mechanisms are not well
      understood. This study analyzes the effect of burn size and burn wound excision
      on CTL activity. METHODS: Anesthetized CBA mice (n = 12) received a 0%, 20%, or
      40% body surface area contact burn. Additional mice (n = 16) received a 40% burn
      that was totally, partially, or not excised 72 hours after burn. Excised areas
      were covered with normal, syngeneic skin. Two weeks later harvested splenocytes
      were cocultured with allogeneic stimulators. CTL activity was determined by a
      51Cr release assay, in which CTL effectors were tested on allogeneic,
      radiolabeled targets. Dilution curves of CTL activity were compared by ANOVA:
      RESULTS: Both 20% and 40% burns significantly inhibited CTL activity (p < 0.05).
      Total but not partial excision of a 40% burn restored CTL activity (p < 0.01).
      Both total and partial wound excision also improved survival (p < 0.05).
      CONCLUSIONS: Burn injury inhibits CTL activity in a size-dependent manner, and
      total wound excision significantly improves both CTL function and survival after
      injury. This study suggests a mechanism for the immunosuppressive effects of burn
      injury and provides an immunologic rationale for early, complete burn wound
      excision.

PMID- 7638762
TI  - Blockade of endothelin-converting enzyme reduces pulmonary hypertension after
      cardiopulmonary bypass and circulatory arrest.
AB  - BACKGROUND: Pulmonary dysfunction associated with elevated pulmonary vascular
      resistance is a significant problem after cardiopulmonary bypass (CPB) and
      circulatory arrest. Mediators of the pulmonary hypertensive response to CPB have
      not been fully elucidated. The purpose of this study was to examine the
      contribution of the endothelium-derived vasoconstrictor endothelin-1 to
      postbypass pulmonary hypertension. METHODS: Twelve 1-month-old piglets were
      instrumented with left atrial and pulmonary artery (PA) micromanometers and a PA
      flow probe. Phosphoramidon (Phos, n = 6) pigs received a 30 mg/kg bolus of Phos,
      an endothelin converting enzyme inhibitor. Controls (n = 6) received saline
      solution. All animals were placed on CPB and underwent a 60-minute period of
      circulatory arrest. The indexed pulmonary vascular resistance (PVRI) was
      calculated at baseline for controls, both before and 10 minutes after drug
      infusion in the Phos group, and 15 minutes after separation from CPB in both
      groups. RESULTS: Pre-CPB, mean PA pressure, and PVRI were not different between
      the control and Phos groups (14.6 +/- 1.1 versus 14.5 +/- 1.1 mm Hg and 7322 +/-
      1269 versus 7260 +/- 947 dyne/sec/kg/cm-5, respectively). After CPB mean PA
      pressure was significantly higher in control than Phos animals (32.1 +/- 1.1
      versus 22.5 +/- 1.3 mm Hg, p = 0.0003). PVRI was also significantly higher in the
      controls (30896 +/- 4714 versus 14972 +/- 1710, dyne/sec/kg/cm-5, p = 0.02).
      CONCLUSIONS: Production of endothelin-1 during CPB and circulatory arrest is a
      mediator of postbypass pulmonary hypertension.

PMID- 7638761
TI  - Interleukin-6 production after thermal injury: evidence for nonmacrophage sources
      in the lung and liver.
AB  - BACKGROUND: Thermal injury induces circulating levels of interleukin-6 (IL-6).
      The liver and lung have been proposed as major sources of IL-6 after injury;
      however, multiple cell types within these organs are capable of IL-6 production.
      In these experiments we further characterize cellular sources of IL-6 after
      thermal injury by examining tissue macrophage response in the liver and lung and
      IL-6 production of cultured pulmonary microvascular endothelial cells (PMECs).
      METHODS: Serum, liver and lung tissue, and tissue macrophage IL-6 response was
      determined in Wistar rats subjected to a 35 to 40% total body surface area scald
      injury. Cultured PMEC IL-6 production was determined after treatment with serum
      from the burned animals. IL-6 bioactivity was assayed by 7TD1 proliferation, and
      IL-6 messenger RNA levels were determined by reverse transcriptase-polymerase
      chain reaction. Alveolar macrophages were obtained by bronchoalveolar lavage.
      Kupffer cells and PMECs were obtained by enzyme digestion of liver and lungs.
      RESULTS: Burn increases circulating IL-6 activity through postburn day 3 (388 +/-
      50 units/0.1 ml versus 80 +/- 12 units/0.1 ml in controls). Burn increases lung
      and liver IL-6 messenger RNA without concurrent increase in the alveolar
      macrophages or Kupffer cells and persists in the lung after bronchoalveolar
      lavage. PMECs cultured in the presence of postburn day 3 serum (10% vol) release
      more IL-6 activity (1118 +/- 333 units/culture versus sham rat serum with 288 +/-
      146 units/culture) than control cultures and have more readily detectable levels
      of IL-6 messenger RNA. CONCLUSIONS: Non-tissue macrophage sources including
      microvascular endothelium may be a contributing source of IL-6 in the lung after
      thermal injury.

PMID- 7638763
TI  - Mechanisms of immature myocardial tolerance to ischemia: phenotypic differences
      in antioxidants, stress proteins, and oxidases.
AB  - BACKGROUND: Previous work has suggested tolerance to ischemic injury in newborn
      myocardium. Although various mechanisms for this protection have been proposed, a
      link between oxidant-antioxidant factors, stress protein expression, and
      protection from cardiac ischemia/reperfusion (I/R) injury has not been made in
      newborn myocardium. We hypothesized total newborn myocardial resistance to I/R is
      related to decreased oxygen radical producing potential, increased free radical
      scavenging capacity and augmented stress protein expression. The purposes of the
      study were to examine in newborn and adult rat hearts (1) functional recovery
      from I/R, (2) catalase and xanthine oxidase (XO) activities, and (3) heat shock
      protein 72 (HSP 72) expression. METHODS: Isolated rat hearts (7 to 10 days versus
      60 days) were perfused on a nonworking Langendorff apparatus at 60 mm Hg (Krebs
      Henseleit buffer, pH 7.4, 37 degrees C) and subjected to 20 minutes of global
      ischemia and 40 minutes of reperfusion. Left ventricular developed pressure was
      recorded by using a left ventricular catheter. Catalase and XO were measured by
      means of standard assays, and HSP 72 was assessed with in situ
      immunohistochemistry. RESULTS: Newborn rat hearts had greater percentage
      functional recovery of left ventricular developed pressure after I/R (66.0% +/-
      4.2% versus 44.3% +/- 3.5%; p < 0.05). The newborn myocardium also had increased
      catalase activity (1027.9 +/- 20.6 units/gm versus 707.3 +/- 38.7 units/gm; p <
      0.05), whereas the activity of XO was decreased relative to the adult (0.23 +/-
      0.01 mU/gm versus 7.6 +/- 1.4 mU/gm; p < 0.05). Furthermore, the expression of
      HSP 72 was greater in the newborn than the adult control. CONCLUSIONS: Relative
      to adult hearts, newborn rat hearts are more tolerant to a global ischemic insult
      followed by reperfusion. This improved functional recovery is associated with
      decreased oxidant production potential (XO), increased scavenging capacity
      (catalase), and augmented stress protein expression (HSP 72).

PMID- 7638764
TI  - Reversal of enhanced pancreatic cancer growth in diabetes by insulin.
AB  - BACKGROUND: Epidemiologic and animal studies have linked pancreatic cancer growth
      with both diabetes and fat intake. This study examined the influence of insulin
      treatment on pancreatic cancer growth in diabetes. Diabetes-induced elevations in
      levels of glucose and free fatty acids were correlated with enhanced tumor growth
      both in vivo and in vitro. METHODS: Hamsters were divided into three groups:
      control (n = 15), streptozocin-diabetic (n = 20), or insulin-treated diabetic (n
      = 20). Diabetes was induced with streptozocin and treated with a continuous
      subcutaneous infusion of insulin delivered via osmotic pumps. Five x 10(5) H2T
      hamster pancreatic cancer cells were implanted into the cheek pouch. Levels of
      plasma glucose and fatty acids were measured, and their effect on H2T cell
      division was assessed in vitro with a spectrophotometric cell proliferation
      assay. RESULTS: Levels of plasma glucose and fatty acids were elevated in
      streptozocin-diabetic animals and normalized with insulin treatment. After 21
      days of growth, tumor weight was 36 mg in the control group, 156 mg in the
      diabetic group (p < 0.01 versus other groups), and 33 mg in the insulin-treated
      diabetic group. In vitro dose-dependent promotion of cell growth was shown for
      glucose (250%), linoleic acid (287%), linolenic acid (169%), and oleic acid
      (98%). CONCLUSIONS: Insulin ameliorated enhanced tumor growth in this model of
      diabetes. Glucose and free fatty acids mobilized during diabetes may serve as
      fuel for established pancreatic cancers.

PMID- 7638766
TI  - Periodontal disease in adult insulin-dependent diabetics.
AB  - The overall objective with the present investigations was to study the influence
      of insulin-dependent diabetes mellitus (IDDM) on periodontal conditions and to
      identify factors that may be predictors for severe periodontal disease in
      individuals with IDDM. Periodontal conditions were studied in two cross-sectional
      studies of adult, insulin-dependent diabetics and age-and sex-matched controls.
      In one study 72 diabetics with short-(SD) and 82 with long-duration (LD) diabetes
      and 77 controls participated. In the other study 83 LD diabetics and 99 controls
      took part. The portion of individuals exhibiting severe periodontal disease was
      larger in the diabetic group than in the control group. Advanced periodontal
      disease appeared in earlier ages (40-49 years) in the LD diabetics compared to
      the SD diabetics and controls. In fact, the 40-49-year-old LD diabetics had
      alveolar bone loss equal to the older controls (60-69 years). LD diabetics
      exhibited more severe periodontitis than SD diabetics. Some salivary factors were
      studied in 72 SD and 82 LD diabetics and 77 controls. LD and SD diabetics had a
      lower stimulated salivary secretion rate and an increased glucose content
      compared to the controls. The reduction in flow rate, however, was moderate, and
      all mean values were within the normal limits. The moderately increased glucose
      content did not result in higher mean numbers of Candida albicans, lactobacilli,
      and mutans streptococci. The subgingival bacterial species currently considered
      to be associated with periodontitis were studied in 30 LD diabetics and 34
      controls. All these bacterial species were recovered in diabetics as well as
      controls. More LD diabetics than controls harboured Porphyromonas gingivalis. In
      the control group the periopathogens were recovered more often in deep
      periodontal pockets. In the LD group, however, these bacterial species were
      recovered as often in shallow as in deep periodontal pockets. The medical status
      of 39 matched pairs of LD diabetics was analysed. One in each pair had severe
      periodontal disease while the other had no/minor symptoms of periodontal disease.
      Biochemical analyses and clinical variables routinely used in monitoring
      diabetics failed to discriminate between diabetics with severe and minor
      periodontal disease. Diabetics with severe periodontal disease, however, showed a
      higher prevalence of renal disease and cardiovascular complications such as
      stroke, transient ischemic attacks, angina, myocardial infarct, heart failure,
      and claudicatio intermittens than diabetics with only minor periodontal disease.
      This indicates that closer cooperation between the diabetologist and the dentist
      is necessary in monitoring the diabetic patient.

PMID- 7638765
TI  - Orthodontic tooth movement and root resorption with special reference to force
      magnitude and duration. A clinical and histological investigation in adolescents.
AB  - The purpose of orthodontic treatment is to move teeth as efficiently as possible
      with least damage to teeth and their supporting tissues. Root resorption may
      occur as an unwanted side effect and may in some instances jeopardize an
      otherwise successful treatment. The general aim of this series of clinical
      investigations was to study the association between applied force, achieved tooth
      movement and related root resorptions. In 144 adolescents, the maxillary first or
      second premolar was buccally moved with a fixed orthodontic appliance. The
      variables studied were duration, magnitude and type of force. Moreover, both the
      occurrence of orthodontically induced root resorptions and the reparative
      potential were investigated in histological preparations of the teeth. When a
      continuous force of a clinically relevant magnitude (50 cN approximately 50 g)
      was applied, tooth movement increased gradually over time. Root resorptions were
      recorded in all test teeth but 4 (93%). After 3 weeks a few teeth revealed root
      resorptions extending half way to the pulp or more in the apical third of the
      root. No association was found between root resorptions and tooth movement.
      Doubling the force magnitude (100 cN approximately 100 g) affected neither the
      tooth movement nor the severity of root resorptions. However, when the force was
      increased 4 times (200 cN approximately 200 g), tooth movement increased 50% but
      still with no significant increase in the occurrence or severity of root
      resorptions. Tooth movement was achieved more efficiently with a continuous force
      than with an interrupted type of force of the same magnitude (50 cN). Root
      resorptions, though, did not seem to be affected differently by the two types of
      forces. Reduction of all types of applied forces was considerable, about 25-30%,
      already within one week. Repair with secondary cementum was recorded almost 3
      times more often after 8 weeks (75%) of retention than after 1 week (28%).
      Irrespective of magnitude and type of force, large individual variations were
      observed regarding tooth movements and root resorptions as well as their
      reparative potential. The possible clinical consequences of the results obtained
      are discussed with regard to cost-benefit effects, convenience to the patient and
      risk of complications.

PMID- 7638767
TI  - [The clinical importance of determining the von Willebrand factor in patients
      with lupus nephritis].
AB  - Venous occlusion test has found out the reserve of vascular and renal endothelium
      in excretion of Willebrand factor in patients with inactive lupus nephritis and
      those with active lupus nephritis with urinary syndrome. In severe active lupus
      nephritis (lupus nephritis with nephrotic syndrome and rapidly progressive lupus
      nephritis) it was not recorded. This fact evidences intensity of immune
      inflammation and coagulation in the kidneys in the above forms of lupus
      nephritis.

PMID- 7638769
TI  - [The use of angiotensin-converting enzyme inhibitors in chronic diffuse kidney
      diseases].
AB  - The treatment with inhibitors of angiotensin-converting enzyme (ACE) was
      conducted in 57 patients with chronic diffuse renal diseases. Of them 45 patients
      received Capoten, 12 patients Renitek. ACE inhibitors were examined for effects
      on arterial pressure, proteinuria, renal and intrarenal hemodynamics. A
      hypotensive effect was apparent in hypertension and minimal in normotension. One
      month later renal bloodflow increased, glomerular filtration rate did not change.
      ACE inhibitors proved able to correct intrarenal hypertension: renal functional
      reserve returned to normal on posttreatment month 1-3 in 10 of 16 patients.
      Noticeable antiproteinuria effect of the drugs emerged 3 months after the
      treatment.

PMID- 7638768
TI  - [Tissue-type plasminogen activator in patients with lupus nephritis].
AB  - ELISA was used to measure tissue plasminogen activator antigen in blood plasma
      and urine of 42 patients with active lupus nephritis (16 with isolated urinary
      syndrome, 13 with nephrotic syndrome, 13 with rapidly progressive LN). Control
      groups consisted of 17 patients with inactive LN and 15 healthy subjects.
      Inhibition of fibrinolysis in vascular system correlating with the disease
      severity was found in patients with active LN. This may result from both
      defective synthesis of tissue plasminogen activator and neutralizing action of
      antiactivator. Urinary fibrinolytic activity was inhibited only in patients with
      rapidly progressive LN because of hyperactive synthesis of antiactivator. The
      above changes occur as endothelial cell dysfunction due to activating and
      damaging action of immune complexes, antibodies, cytokines on vascular
      endothelium. Zero activator activity of plasma and urine in patients with active
      LN reflects severe dysfunction of endothelial cell caused by its structural
      disorganization.

PMID- 7638770
TI  - [The dynamic importance of proteinuria and arterial pressure for detecting late
      toxicosis in pregnant women with chronic kidney diseases and hypertension].
AB  - Time course of 187 pregnancies was followed up in 103 females with chronic renal
      diseases (CRD), 76 females with essential hypertension (EH) and 14 posteclampsia
      females. Three variants of arterial pressure (AP) and 5 types of proteinuria
      changes were recognized in CRD and EH patients. The pattern of these changes was
      compared to that in posteclampsia patients, the eclampsia being an absolute
      criterium of late toxicosis. It is shown that neither elevated AP and proteinuria
      nor their absolute values can serve reliable signs of late gestosis in CRD and EH
      patients. Only the trend in these parameters is significant. CRD and EH females
      with late gestosis exhibit rapidly growing proteinuria in line with the onset or
      exacerbation of EH. Retrospective analysis of the pregnancies has confirmed
      association of late gestosis in 15% of EH and 7% of chronic glomerulonephritis
      patients. These estimates are lower than commonly accepted. Early diagnosis of
      late gestosis in pregnant females with CRD and EH requires not only regular AP
      registration, but also dynamic, in some cases hourly, evaluation of proteinuria.

PMID- 7638771
TI  - [The efficacy of an erythropoietin-calcitriol combination in patients with
      chronic kidney failure on programmed hemodialysis].
AB  - In 8 patients with chronic renal failure (CRF) on hemodialysis combined therapy
      (erythropoietin+calcitriol) effect was evaluated versus control group of 9
      hemodialysis patients on erythropoietin monotherapy. In patients on the combined
      regimen the antianemic effect occurred sooner, this effect of calcitriol coming
      prior to correction of uremic defects in phosphoric-calcium metabolism.
      Calcitriol mechanisms of action in renal anemia and benefits of potential
      calcitriol+erythropoietin combination use in CRF patients suffering from uremic
      osteodystrophy, hypercatabolic conditions, uremic hypogonadism and infection
      complications are discussed.

PMID- 7638772
TI  - [On the centenary of the birth of Evgenii Mikhaiklovich Tareev].

PMID- 7638773
TI  - [Tubulointerstitial nephritis in chronic viral diseases of the liver].
AB  - The paper reports 4 cases of tubulointerstitial nephritis (TIN) in chronic
      diffuse diseases of the liver (CDDL). The latter comprised such conditions of
      virus etiology as chronic active hepatitis, chronic lobular hepatitis. TIN
      presented with pronounced renal tubular affections: defects of concentration
      capacity, distal renal tubular acidosis, renal diabetes insipidus. In 3 cases
      renal lesions occurred 1 and 6 years prior to CDDL detection. TIN pathogenesis in
      CDDL of viral etiology is discussed.

PMID- 7638774
TI  - [Kidney involvement in industrial exposure to lead and cadmium].

PMID- 7638775
TI  - [Acute kidney failure related to the use of x-ray contrast agents and
      indomethacin: the risk factors and mechanisms of its development].
AB  - 7 acute renal failure (ARF) and experiments provided information on ARF induced
      by radio-opaque substances and indomethacin. The leading mechanism underlying
      renal failure is supposed to be the spasm of renal afferent arterioles secondary
      to hypercalcemia, prostaglandin synthesis blockade, activation of renin
      angiotensin system and high activity of adenosine.

PMID- 7638776
TI  - [The current concepts of microscopic polyarteritis].
AB  - Clinical picture, morphological changes, immunological disorders confirm reality
      and nosological independence of MPA. A clear nosological differentiation of
      systemic vasculitis is important for decision on an individual choice of
      treatment.

PMID- 7638777
TI  - [Vasculopathy in patients with systemic lupus erythematosus and the
      antiphospholipid syndrome].
AB  - Clinicomorphological examination covered 100 patients with confirmed SLE: 79 with
      concomitant APS (group 1), 21 free of APS (group 2). In group 1 thrombolytic
      complications occurred in 75%, in group 2- in 13%. The recurrences were more
      frequent in group 1. Overall percentage of arterial and venous thromboses was
      approximately the same. According to biopsy and autopsy 2 kinds of morphological
      changes were found: typical for SLE and APS. Morphological specificity of APS
      manifested with proliferative and thrombotic changes in both arteries and veins.

PMID- 7638778
TI  - [The long-term parenteral use of cyclophosphane in treating patients with
      systemic lupus erythematosus and central nervous system involvement].
AB  - In the treatment of systemic lupus erythematosus (SLE) with acute CNS affections
      good results may be obtained with intravenous cyclophosphamide (CP) +
      methylprednisolone followed with long-term parenteral CP administration. CNS
      abnormalities in SLE patients can be effectively managed by parenteral CP in
      combination with minimal-dose glucocorticoids given for 5-7 years.

PMID- 7638779
TI  - [Does the basic therapy affect the development of secondary amyloidosis in
      rheumatoid arthritis?].
AB  - Anti-rheumatic drug treatments were studied in 260 patients from Finland and
      Russia suffering from rheumatoid arthritis (RA) with or without biopsy-proven
      secondary amyloidosis (RSA). Chloroquine was used for longer period in RSA group
      in Russia (p = 0.003) and in Finland (p = 0.06). In Finland chloroquine was used
      more often in the RSA group (p = 0.02), and sulphasalazine (p = 0.02), D
      penicillamine (p = 0.03) and cytotoxics (p = 0.04) in the control group. The role
      of therapy in the prevention of RSA in chronic inflammation is discussed.

PMID- 7638780
TI  - [Nephritis in middle-aged and elderly subjects].

PMID- 7638781
TI  - [The evolution of the concepts of systemic scleroderma].

PMID- 7638782
TI  - [Antiendothelial antibodies in systemic scleroderma and Raynaud's disease].
AB  - Using ELISA on fixed endothelial hybridoma (EAhy.926) cells we investigated the
      occurrence of antiendothelial antibodies (AEA) in the sera from patients with
      scleroderma systematica (SS) (n = 70) and Raynaud's disease (RD) (n = 19). The
      mean IgG and IgA-AEA levels were significantly higher in the SS patients than RD
      patients (p < 0.001) and controls (p < 0.001). We have detected circulating IgG
      AEA in 64.2% of patients with SS, 35.2% of SS sera were positive for IgA-AEA. In
      patients with RD, the frequency of AEA corresponded to that of the random
      population sample. We have found a high incidence of Raynaud's phenomenon,
      myositis, telangiectasia and marked digital ischaemia (digital ischemic pulp
      ulcers, digital scars, osteolysis and autoamputation) among AEA positive patients
      with SS. AEA-positive patients were characterized by high extent and severity of
      Raynaud's phenomenon and higher average nailfold capillary microscopy scores. No
      correlations were found between AEA and different clinical or laboratory
      parameters, including the type of scleroderma (diffuse and limited), the presence
      of anti-Scl-7O and anticentromere antibodies and the clinical features of SS
      (lungs, kidneys and heart involvement, esophageal dysfunction, calcinosis,
      Sjogren's syndrome). There was no significant correlation between the AEA level
      and patient age, extent of skin involvement (skin score). Thus, in SS, AEA is
      associated with a peripheral vasculopathy and represent a useful marker for the
      diagnosis of endothelial dysfunction.

PMID- 7638783
TI  - [Oncogenic osteomalacia: its pathogenesis, clinical picture and treatment].
AB  - A female of 53 and male of 35 complained of myasthenia and pain in the bones.
      Biochemically, they had severe hypophosphatemia secondary to a sharp decline in
      tubular reabsorption of phosphates. X-ray showed tumor of bone tissue. The
      patients were diagnosed to have oncogenic osteomalacia. Literature data on
      pathogenesis, clinical features and treatment of this rare disease are reviewed.

PMID- 7638784
TI  - [Myocardial scintigraphy with thallium-201 in the diagnosis of cardiac
      involvement in systemic scleroderma].
AB  - 201Tl scintigraphy of the myocardium is a highly sensitive method of diagnosis of
      cardiac damage in SS. More severe lesions occur in patients with diffuse skin
      affections and subacute SS. Improvement of perfusion in dipiridamol test
      indicates the contribution of the spasm of microcirculation coronary vessels to
      the onset of perfusion defects. Further investigations are needed for evaluation
      of the role various vasodilators have in prevention of perfusion lesions and
      progressive myocardial fibrosis in SS patients.

PMID- 7638785
TI  - [Approaches to predicting the course and outcome of subacute infectious
      endocarditis].

PMID- 7638786
TI  - [Interstitial lung diseases--the clinical aspects of the problem].
AB  - Upon analysis of 550 cases of different chronic diffuse pulmonary diseases
      included in a group of interstitial diseases of the lungs (IDL) the authors came
      to the conclusion that IDL incorporate such variants as alveolitis, pulmonary
      vasculitis and pulmonary hemorrhages; granulomatosis covers exogenic allergic
      alveolitis, alveolitis in chronic active hepatitis; vasculitis group includes
      such rare diseases as necrotizing sarcoid granulomatosis vasculitis and lymphoid
      granulomatosis; fibrosing alveolitis--secondary alveolitis in sclerodermia
      systematica, rheumatoid arthritis, Sjogren's disease, chronic active hepatitis.
      Knowledge of IDL etiology (environmental, occupational, induced by radionuclides,
      drugs, viruses, fungi) with focus on drug affection of the lungs is thought of
      value. Biopsy and bronchial lavage findings are compared clinically and
      morphologically. Mechanisms of pulmonary fibrosis and approaches to inhibition of
      pulmonary fibrosis progression are outlined.

PMID- 7638787
TI  - [Variants and stages in the course of idiopathic fibrosing alveolitis].
AB  - Clinicomorphological analysis covered 41 cases of idiopathic fibrosing alveolitis
      (IFA). The comparison of the degree of respiratory insufficiency, hypoxia,
      survival of the patients with cytogram of the bronchoalveolar lavage,
      morphological findings, generation of active oxygen forms by alveolar macrophages
      and leukocytes has provided evidence on an important role of alveolar macrophage
      in interstitial alveolitis and fibrosis in IFA. Three variants of chronic IFA are
      distinguished: aggressive, persistent and slowly progressive. The variants have
      different prognosis and need individual therapeutic approach.

PMID- 7638788
TI  - [The use of ramipril in treating patients with chronic heart failure].

PMID- 7638789
TI  - [Chronic viral diseases of the liver: their patho- and morphogenesis and clinical
      characteristics].

PMID- 7638790
TI  - [Kidney involvement in lymphosarcomas].

PMID- 7638791
TI  - [A rare case of a combination of hereditary amyloidosis and sarcoidosis].

PMID- 7638792
TI  - [The successful treatment of chronic active hepatitis due to hepatitis C viral
      infection with alpha-interferon and a cytokine complex (a clinical case)].

PMID- 7638793
TI  - [The development of diffuse cholangiocarcinoma in a female patient with long-term
      undiagnosed Wilson's disease].

PMID- 7638794
TI  - [Thrombocytopenia in patients with lupus nephritis].
AB  - 60 patients with lupus nephritis (LN) were examined for frequency of
      thrombocytopenia, role of IgG and IgM antibodies to cardiolipin (AC),
      antithrombocytic antibodies (AA) and anaerobic platelet metabolism.
      Thrombocytopenia occurred in 28 (46.7%) patients, it was 2 times more frequent in
      active LN patients with AC than in those free of AC. AA were recorded in 36.6% of
      patients (32.2% versus 37.5% for patients with thrombocytopenia and free of it,
      respectively). In active LN platelet activity and metabolism became enhanced.
      Genesis of thrombocytopenia in various LN forms may be induced by different
      mechanisms.

PMID- 7638795
TI  - Tuberculous pleurisy and adenosine deaminase.

PMID- 7638796
TI  - Long-term nasal ventilation.

PMID- 7638797
TI  - Who should look after asthma?

PMID- 7638798
TI  - Value of adenosine deaminase in the diagnosis of tuberculous pleural effusions in
      young patients in a region of high prevalence of tuberculosis.
AB  - BACKGROUND: Pleural biopsy is usually considered important for the diagnosis of
      pleural effusions, especially for distinguishing between tuberculosis and
      neoplasia, even though tuberculous pleural fluid contains sensitive biochemical
      markers. In regions with a high prevalence of tuberculosis, and in patient groups
      with a low risk of other causes of pleurisy, the positive predictive value of
      these markers is increased. The criteria for performing a pleural biopsy under
      these circumstances have been investigated, using adenosine deaminase (ADA) as a
      pleural fluid marker for tuberculosis. METHODS: One hundred and twenty nine
      patients with a pleural effusion aged < or = 35 years (mean (SD) 25.2 (4.9)
      years) were studied. Seventy three were men. Eighty one effusions (62.8%) were
      tuberculous, 12 (9.3%) parapneumonic, and 10 (7.7%) neoplastic, five were caused
      by pulmonary thromboembolism, four by systemic lupus erythematosus, seven by
      empyema, three following surgery, one was the result of asbestosis, and one of
      nephrotic syndrome. In five cases no definitive diagnosis was reached. ADA levels
      were determined by the method of Galanti and Giusti. RESULTS: The diagnostic
      yield of procedures not involving biopsy was 94.5% (122/129). Pleural biopsy
      provided a diagnosis in a further two cases, but not in the remaining five. All
      tuberculous cases had pleural fluid levels of ADA of > 47 U/l (mean (SD) 111.1
      (36.6) U/l). The only other cases in which ADA exceeded this level were six of
      the seven patients with empyema. Cytological examination of the pleural fluid
      diagnosed eight of the 10 neoplastic cases, compared with six diagnosed by
      pleural biopsy. CONCLUSIONS: In a region with a high prevalence of tuberculosis
      procedures not involving pleural biopsy have a very high diagnostic yield in
      patients with a pleural effusion aged < or = 35 years, making biopsy necessary
      only in cases in which pleural levels of ADA are below 47 U/l, pleural fluid
      cytology is negative and, in the absence of a positive basis for some other
      diagnosis, neoplasia is suspected.

PMID- 7638799
TI  - Outcome of domiciliary nasal intermittent positive pressure ventilation in
      restrictive and obstructive disorders.
AB  - BACKGROUND: Nasal intermittent positive pressure ventilation (NIPPV) is a new
      technique which has rapidly supplanted other non-invasive methods of ventilation
      over the last 5-10 years. Data on its effectiveness are limited. METHODS: The
      outcome of long term domiciliary NIPPV has been analysed in 180 patients with
      hypercapnic respiratory failure predominantly due to chest wall restriction,
      neuromuscular disorders, or chronic obstructive lung disease. One hundred and
      thirty eight patients were started on NIPPV electively, and 42 following an acute
      hypercapnic exacerbation. Outcome measures were survival (five year probability
      of continuing NIPPV), pulmonary function, and health status. A crossover study
      from negative pressure ventilation to NIPPV was carried out in a subgroup of
      patients. RESULTS: Five year acturial probability of continuing NIPPV for
      individuals with early onset scoliosis (n = 47), previous poliomyelitis (n = 30),
      following tuberculous lung disease (n = 20), general neuromuscular disorders (n =
      29), and chronic obstructive pulmonary disease (n = 33) was 79% (95% CI 66 to
      92), 100%, 94% (95% CI 83 to 100), 81% (95% CI 61 to 100), 43% (95% CI 6 to 80),
      respectively. Most of the patients with bronchiectasis died within two years. One
      year after starting NIPPV electively the mean (SD) PaO2 compared with the
      pretreatment value was +1.8 (1.9) kPa, mean PaCO2 -1.4 (1.3) kPa in patients with
      extrapulmonary restrictive disorders, and PaO2 +0.8 (1.0) kPa, PaCO2 -0.9 (0.8)
      kPa in patients with obstructive lung disease. Arterial blood gas tensions
      improved in patients transferred from negative pressure ventilation to NIPPV.
      Health status was ranked highest in patients with early onset scoliosis, previous
      poliomyelitis, and following tuberculous lung disease. In the group as a whole
      health perception was comparable to outpatients with other chronic disorders.
      CONCLUSIONS: The long term outcome of domiciliary NIPPV in patients with chronic
      respiratory failure due to scoliosis, previous poliomyelitis, and chest wall and
      pulmonary disease secondary to tuberculosis is encouraging. The results of NIPPV
      in patients with COPD and progressive neuromuscular disorders show benefit in
      some subgroups. The outcome in end stage bronchiectasis is poor.

PMID- 7638800
TI  - Nocturnal saturation and respiratory muscle function in patients with chronic
      obstructive pulmonary disease.
AB  - BACKGROUND: Nocturnal desaturations, mainly caused by hypoventilation, occur
      frequently in patients with chronic obstructive pulmonary disease (COPD). Daytime
      arterial oxygen and carbon dioxide tensions (PaO2 and PaCO2) appear to predict
      which patients will desaturate at night. It is unknown if respiratory muscle
      strength, which may be decreased in these patients, plays an additional part.
      METHODS: Polysomnography, maximal respiratory pressures, lung function, and
      arterial blood gas tensions were measured in 34 patients with COPD (mean (SD)
      forced expiratory volume in one second (FEV1) 41.7 (19.9)% pred). RESULTS:
      Significant correlations were found between the mean nocturnal arterial oxygen
      saturation and maximal inspiratory mouth pressure (r = 0.65), maximal inspiratory
      transdiaphragmatic pressure (r = 0.53), FEV1 (r = 0.61), transfer coefficient
      (KCO) (r = 0.38), arterial oxygen saturation (SaO2) (r = 0.75), and PaCO2 (r = 
      0.44). Multiple regression analysis showed that 75% of the variance in nocturnal
      SaO2 (70%) and FEV1 (5%). CONCLUSION: Inspiratory muscle strength and nocturnal
      saturation data are correlated, but daytime SaO2 and FEV1 remain the most
      important predictors of nocturnal saturation.

PMID- 7638802
TI  - Mouth pressure in response to magnetic stimulation of the phrenic nerves.
AB  - BACKGROUND: Diaphragm strength can be assessed by the measurement of gastric (TW
      PGA), oesophageal (TW POES), and transdiaphragmatic (TW PDI) pressure in response
      to phrenic nerve stimulation. However, this requires the passage of two balloon
      catheters. A less invasive method of assessing diaphragm contractility during
      stimulation of the phrenic nerves would be of clinical value. A study was
      undertaken to determine whether pressure measured at the mouth (TW PM) during
      magnetic stimulation of the phrenic nerves accurately reflects TW POES, and to
      investigate the relations between TW PM and TW PDI; and also to see whether
      glottic closure and twitch potentiation can be avoided during these measurements.
      METHODS: Eight normal subjects and eight patients with suspected respiratory
      muscle weakness without lung disease were studied. To prevent glottic closure
      magnetic stimulation of the phrenic nerves was performed at functional residual
      capacity during a gentle expiratory effort against an occluded airway
      incorporating a small leak. TW PDI, TW POES, and TW PM were recorded. Care was
      taken to avoid potentiation of the diaphragm. RESULTS: In normal subjects mean TW
      PM was 13.7 cm H2O (range 11.3-16.1) and TW POES was 13.3 cm H2O (range 10.4
      15.9) with a mean (SD) difference of 0.4 (0.81) cm H2O. In patients mean TW PM
      was 9.1 cm H2O (range 0.5-18.2) and TW POES was 9.3 (range 0.7-18.7) with a mean
      (SD) difference of -0.2 (0.84) cm H2O. The relation between TW PM and TW PDI was
      less close but was well described by a linear function. In patients with
      diaphragm weakness (low sniff PDI) TW PM was < 10 cm H2O. CONCLUSIONS: TW PM
      reliably reflects TW POES and can be used to predict TW PDI in normal subjects
      and patients without lung disease. TW PM may therefore be a promising non
      invasive, non-volitional technique for the assessment of diaphragm strength.

PMID- 7638801
TI  - Sleep apnoea in patients with quadriplegia.
AB  - BACKGROUND: This study was undertaken to establish the prevalence of, and the
      factors contributing towards, sleep disordered breathing in patients with
      quadriplegia. METHODS: Forty representative quadriplegic patients (time since
      injury > 6 months, injury level C8 and above, Frankel category A, B, or C; mean
      (SE) age 35.0 (1.7) years) had home sleep studies in which EEG, EOG, submental
      EMG, body movement, nasal airflow, respiratory effort, and pulse oximetry (SpO2)
      were measured. Patients reporting post traumatic amnesia of > 24 hours, drug or
      alcohol abuse or other major medical illness were excluded from the study. A
      questionnaire on medications and sleep was administered and supine blood
      pressure, awake SpO2, spirometric values, height, and neck circumference were
      measured. RESULTS: A pattern of sustained hypoventilation was not observed in any
      of the patients. Sleep apnoeas and hypopnoeas were, however, common. Eleven
      patients (27.5%) had a respiratory disturbance index (RDI, apnoeas plus
      hypopnoeas per hour of sleep) of > or = 15, with nadir SpO2 ranging from 49% to
      95%. Twelve of the 40 (30%) had an apnoea index (AI) of > or = 5 and, of these,
      nine (75%) had predominantly obstructive apnoeas-that is, > 80% of apnoeas were
      obstructive or mixed. This represents a prevalence of sleep disordered breathing
      more than twice that observed in normal populations. For the study population RDI
      correlated with systolic and diastolic blood pressure and neck circumference. RDI
      was higher in patients who slept supine compared with those in other postures.
      Daytime sleepiness was a common complaint in the study population and sleep
      architecture was considerably disturbed with decreased REM sleep and increased
      stage 1 non-REM sleep. CONCLUSIONS: Sleep disordered breathing is common in
      quadriplegic patients and sleep disturbance is significant. The predominant type
      of apnoea is obstructive. As with non-quadriplegic patients with sleep apnoea,
      sleep disordered breathing in quadriplegics is associated with increased neck
      circumference and the supine sleep posture.

PMID- 7638803
TI  - Respiratory muscle strength in chronic heart failure.
AB  - BACKGROUND: Several studies have suggested that the respiratory muscles are weak
      in patients with heart failure, but the aetiology and clinical relevance of this
      weakness are unclear. In order to see if respiratory muscle weakness in this
      context is part of a more generalised myopathic process, respiratory and limb
      muscle strength were compared in patients with heart failure. The relation
      between respiratory muscle strength, breathlessness on exercise, and exercise
      capacity was also examined. METHODS: Twenty patients (three women) with New York
      Heart Association (NYHA) class II-IV heart failure of mean age 63 years were
      studied. Respiratory muscle strength was assessed using maximum inspiratory and
      expiratory mouth pressures (MIP and MEP) and transdiaphragmatic pressure during
      sniffs (sniff PDI). These parameters were compared with cardiac output (indirect
      Fick) and with limb muscle strength as assessed by grip strength. The patients
      also performed two exercise tests during which they rated their breathlessness on
      a Borg scale. RESULTS: Mean (SD) cardiac index was 2.2 (0.4) l/min/m2. MIP and
      MEP were 66 (27) and 99 (29) cm H2O respectively. Sniff PDI was 103 (21) cm H2O
      and was positively correlated with grip strength and cardiac output (Spearman
      rank correlation coefficients 0.527 and 0.451, respectively). None of the indices
      of respiratory muscle strength were related to exercise time or breathlessness
      during exercise. CONCLUSIONS: The respiratory muscles are weak in patients with
      heart failure. This weakness reflects a more generalised myopathic process,
      possibly related to reduced cardiac output. However, respiratory muscle weakness
      does not appear to be an important factor in the aetiology of breathlessness on
      exercise.

PMID- 7638804
TI  - Lack of effect of inhaled morphine on exercise-induced breathlessness in chronic
      obstructive pulmonary disease.
AB  - BACKGROUND: Inhaled nebulised morphine may reduce breathlessness in patients with
      lung disease, although the results of controlled trials are conflicting. A direct
      action of morphine on the lung has been postulated. This study aimed to
      investigate whether nebulised morphine reduced exercise-induced breathlessness in
      patients with chronic obstructive pulmonary disease (COPD) and to determine if
      this was a local pulmonary effect or occurred after systemic morphine absorption.
      METHODS: A double blind, randomised, crossover study was performed in 12 men with
      COPD to compare the effects of nebulised morphine (10 and 25 mg), equivalent
      intravenous doses (1 and 2.5 mg), and placebo. Breathlessness (visual analogue
      scale), ventilation, gas exchange, and exercise endurance were measured during
      graded bicycle exercise. RESULTS: None of the treatments altered breathlessness,
      ventilation, or gas exchange at rest or at any time during exercise, and exercise
      endurance was unaffected. At peak exercise mean (95% CI) changes from placebo in
      ventilation were -0.8 (-0.57 to 1.1) l/min and -0.4 (-2.8 to 2.0) l/min for the
      highest intravenous and nebulised doses, respectively. For breathlessness
      equivalent values were +2 (-5 to 9) and +1 (-9 to 11) mm. The study was of
      sufficient power that it is unlikely that a clinically important effect was
      missed. CONCLUSIONS: Nebulised morphine in these doses has no effect on exercise
      induced breathlessness. These findings do not support the hypothesis that
      intrapulmonary opiates modulate the sensation of breathlessness in patients with
      COPD.

PMID- 7638805
TI  - Differences in aerosol output and airways responsiveness between the DeVilbiss 40
      and 45 hand held nebulisers.
AB  - BACKGROUND: The DeVilbiss 40 glass hand held nebulisers have been widely used for
      airways responsiveness testing in epidemiological surveys of asthma. These
      nebulisers have been superseded in some recent studies by the DeVilbiss 45
      plastic hand held nebulisers with the assumption that they are interchangeable.
      This study compared the aerosol outputs of the DeVilbiss 40 and DeVilbiss 45
      nebulisers and investigated whether there was any difference in the in vivo
      measurements of airways responsiveness when using the two nebuliser types.
      METHODS: The aerosol output of six DeVilbiss 40 and six DeVilbiss 45 nebulisers
      was calculated by weight loss per actuation, the usual method of calibrating
      nebuliser output, and compared with the true amount of aerosol obtained measured
      by a flouride tracer technique. Airways responsiveness was measured twice in 13
      asthmatic patients under identical conditions by the Yan protocol using DeVilbiss
      40 and 45 nebulisers in random order. RESULTS: Weight loss overestimated the true
      aerosol output of both types of nebulisers. Weight loss was similar for the
      DeVilbiss 40 and 45 nebulisers but the true aerosol output of the DeVilbiss 45
      was nearly twice that of the DeVilbiss 40 nebuliser. The geometric mean PD20
      values with the DeVilbiss 40 nebuliser was a mean 1.7 doubling doses of histamine
      higher than that obtained with the DeVilbiss 45 nebuliser. CONCLUSIONS: The
      DeVilbiss 40 and 45 nebulisers should not be used interchangeably for airways
      responsiveness testing merely because their outputs based on weight loss are
      similar. Artefactual differences in the prevalence rates of airways
      responsiveness could occur in longitudinal studies if a change was inadvertently
      made from using DeVilbiss 40 to DeVilbiss 45 nebulisers.

PMID- 7638806
TI  - Aerosol deposition in the human lung following administration from a
      microprocessor controlled pressurised metered dose inhaler.
AB  - BACKGROUND: Gamma scintigraphy was employed to assess the deposition of aerosols
      emitted from a pressurised metered dose inhaler (MDI) contained in a
      microprocessor controlled device (SmartMist), a system which analyses an
      inspiratory flow profile and automatically actuates the MDI when predefined
      conditions of flow rate and cumulative inspired volume coincide. METHODS:
      Micronised salbutamol particles contained in a commercial MDI (Ventolin) were
      labelled with 99m-technetium using a method validated by the determination of (1)
      aerosol size characteristics of the drug and radiotracer following actuation into
      an eight stage cascade impactor and (2) shot potencies of these non-volatile
      components as a function of actuation number. Using nine healthy volunteers in a
      randomised factorial interaction design the effect of inspiratory flow rate
      (slow, 30 l/min; medium, 90 l/min; fast, 270 l/min) combined with cumulative
      inspired volume (early, 300 ml; late, 3000 ml) was determined on total and
      regional aerosol lung deposition using the technique of gamma scintigraphy.
      RESULTS: The SmartMist firing at the medium/early setting (medium flow and early
      in the cumulative inspired volume) resulted in the highest lung deposition at
      18.6 (1.42)%. The slow/early setting gave the second highest deposition at 14.1
      (2.06)% with the fast/late setting resulting in the lowest (7.6 (1.15)%).
      Peripheral lung deposition obtained for the medium/early (9.1 (0.9)%) and
      slow/early (7.5 (1.06)%) settings were equivalent but higher than those obtained
      with the other treatments. This reflected the lower total lung deposition at
      these other settings as no difference in regional deposition, expressed as a
      volume corrected central zone:peripheral zone ratio, was apparent for all modes
      of inhalation studied. CONCLUSIONS: The SmartMist device allowed reproducible
      actuation of an MDI at a preprogrammed point during inspiration. The extent of
      aerosol deposition in the lung is affected by a change in firing point and is
      promoted by an inhaled flow rate of up to 90 l/min-that is, the slow and medium
      setting used in these studies.

PMID- 7638807
TI  - Pulmonary deposition and disappearance of aerosolised secretory leucocyte
      protease inhibitor.
AB  - BACKGROUND: The neutrophil elastase inhibitor, secretory leucocyte protease
      inhibitor (SLPI), is a potential therapeutic tool in inflammatory lung diseases
      such as cystic fibrosis and pulmonary emphysema. The distribution and
      disappearance in the lung of aerosolised recombinant SLPI (rSLPI) was
      investigated in healthy humans and in patients with cystic fibrosis or alpha 1
      antitrypsin-associated emphysema. METHODS: To distinguish aerosolised rSLPI from
      endogenous SLPI the recombinant inhibitor was radiolabelled with 99m-technetium
      (99mTc) pertechnetate. Distribution and disappearance of aerosolised 99mTc-rSLPI
      in the lungs were studied by gamma radiation imaging. RESULTS: The deposition of
      99mTc-rSLPI in normal volunteers was homogeneous in all lung lobes, while in
      patients with cystic fibrosis or emphysema only well ventilated areas showed
      deposition of the aerosol. The disappearance rate of 99mTc-rSLPI was
      biexponential. The half life of the rapid phase was 0.2-2.8 hours, while that of
      the slow phase was more than 24 hours. CONCLUSIONS: Future aerosol therapy with
      rSLPI will be most beneficial for well ventilated lung tissue that needs
      protection against neutrophil derived elastase. It may be more difficult to
      neutralise the burden of elastase in poorly ventilated, highly inflamed areas as
      are seen in cystic fibrosis.

PMID- 7638808
TI  - Effect of cigarette smoke on the mRNA and protein expression of carcinoembryonic
      antigen (CEA), a possible chemoattractant for neutrophils in human
      bronchioloalveolar tissues.
AB  - BACKGROUND: The concentration of carcinoembryonic antigen (CEA), known as a
      marker of malignant transformation and chronic inflammation, is increased in
      bronchoalveolar lavage fluid obtained from smokers compared with fluid from non
      smokers. This study investigated the mechanism and biological significance of CEA
      production in the lungs of smokers by evaluating protein and mRNA expression in
      non-carcinomatous lung parenchymal tissues and in cell lines derived from human
      fetal lung. METHODS: Lung parenchymal tissue free from cancer or an inflammatory
      lesion was obtained from five non-smokers (four with lung cancer, one with
      pulmonary mycetoma), five ex-smokers (all with lung cancer except for one with
      mesothelioma), and 14 smokers (nine with lung cancer, five with emphysema) at
      surgery or necropsy. Cancer tissue was also collected simultaneously from the
      subjects with lung cancer. CEA protein in the tissue homogenates was measured by
      enzyme linked immunoassay. CEA mRNA expression in the non-carcinomatous
      parenchymal tissue and cancer tissue was evaluated by in situ hybridisation using
      CEA specific riboprobe and was semiquantitated by counting the number of silver
      grains per cell. CEA mRNA expression was also compared in three cell lines
      derived from human fetal lung (IMR-90, MRC-9, and CCD-14Br) after in vitro
      stimulation with medium exposed to cigarette smoke or air. Chemoattractant
      activity of purified CEA for neutrophils and monocytes was also studied in vitro.
      RESULTS: CEA content in non-carcinomatous lung tissue was increased in smokers
      with emphysema (mean (SD) 38.0 (9.2) ng/mg protein) or with lung cancer (38.2
      (21.6)) compared with non-smokers (11.0 (5.4)) or ex-smokers (5.9 (2.2)). CEA
      mRNA expression in non-carcinomatous tissue, expressed by average number of
      grains per cell, was also increased in smokers with emphysema (mean (SD) 11.2
      (4.1)) or with lung cancer (14.0 (8.4)) compared with non-smokers (3.1 (0.6)) or
      ex-smokers (4.0 (1.7)). CEA content in carcinomatous tissues was 42.8 (37.3) for
      non-smokers, 38.2 (42.4)) for ex-smokers, and 59.0 (22.5) for smokers. The CEA
      content in carcinomatous tissue was higher than in non-carcinomatous tissue, but
      there was no difference between non-smokers, ex-smokers, and smokers. The numbers
      of grains per cell in carcinomatous tissue were higher than in non-carcinomatous
      tissues, but not different among non-smokers (30.3 (3.9)), ex-smokers (38.3
      (13.8)), and smokers (44.3 (5.2)). CEA mRNA expression in the cell lines was
      upregulated after the incubation with smoke-treated medium. Purified CEA was
      chemoattractant for neutrophils but not for monocytes in vitro. CONCLUSIONS: mRNA
      and protein expression of CEA were increased in the normal lung tissue from
      smokers compared with non-smokers or ex-smokers. Since CEA content and mRNA
      expression were no different between smokers with non-small cell lung cancer and
      those with non-carcinomatous disease, it is unlikely that CEA expression in non
      carcinomatous lung parenchymal tissue was influenced by the presence of the
      tumour and is consistent with the effect of smoking. This is supported by in
      vitro studies which show that cigarette smoke could induce CEA mRNA expression in
      fetal lung derived cells. In addition, CEA might play a part in recruitment of
      neutrophils into the lower respiratory tract.

PMID- 7638809
TI  - Bronchus-associated lymphoid tissue (BALT) in the lungs of children who had died
      from sudden infant death syndrome and other causes.
AB  - BACKGROUND: Bronchus-associated lymphoid tissue (BALT) is well characterised in
      rabbits and rats. In humans, however, it does not seem to be present in the
      healthy adult lung, although it can develop after certain microbial stimulation.
      METHODS: In the present study a consecutive series of lungs from 88 children who
      had died of sudden infant death syndrome (SIDS) and 34 control cases of
      comparable age were examined for the presence of BALT. RESULTS: BALT was present
      in 36.4% of the patients who had died of SIDS and in 44.1% of the control cases.
      The probability of finding BALT increased with age, with similar kinetics in both
      groups. CONCLUSIONS: Future studies need to define when and at what rate BALT
      disappears as children get older. In young children BALT may act as an entry site
      for antigens to initiate an immune response, as is well documented for the gut
      associated lymphoid system.

PMID- 7638810
TI  - Neutrophil sequestration in rat lungs.
AB  - BACKGROUND: The transit of neutrophils through the pulmonary microvasculature is
      prolonged compared with red blood cells and is increased further during cigarette
      smoking and in exacerbations of chronic obstructive pulmonary disease. The
      increased residence time (sequestration) of neutrophils in the pulmonary
      capillaries in these conditions may be the first step leading to the accumulation
      of cells within the lung interstitium and in the bronchoalveolar space, so
      potentiating lung damage. A rat model has been developed to investigate the
      factors which may influence neutrophil transit through the lung microvasculature.
      METHODS: Intratracheal instillation of the heat killed organism Corynebacterium
      parvum was used to induce an acute neutrophil alveolitis. Neutrophils and red
      blood cells were isolated from donor rats, labelled with two distinct
      radioisotopes, and then reinjected into recipient rats to assess their transit
      through the pulmonary circulation. To ascertain whether peripheral blood
      neutrophils were minimally altered by the isolation procedure their functional
      status in vitro was compared with that of inflammatory neutrophils in a number of
      assays commonly used as descriptors of neutrophil activation. The influence of
      neutrophil activation on the accumulation of cells in the lungs was assessed by
      comparing the lung sequestration of control neutrophils, isolated from peripheral
      blood, with that of inflammatory neutrophils obtained from bronchoalveolar lavage
      of inflamed rat lungs. Lung sequestration of neutrophils was defined as the fold
      increase in the ratio of neutrophils labelled with chromium-51 to red blood cells
      labelled with technetium-99m in lung tissue compared with the same ratio in
      peripheral blood. RESULTS: Sequestration of peripheral blood neutrophils occurred
      in control rat lungs as shown by a 17.5 (2.1) fold increase in the ratio of
      neutrophils to red blood cells in the pulmonary circulation compared with the
      ratio of these cells in the peripheral circulation. When inflammatory
      neutrophils, obtained by bronchoalveolar lavage from C parvum-treated animals,
      were injected into control rats, the increase was 90.6 (11.0) fold. Induction of
      an inflammatory response in the lung tissue of the recipient rat also caused an
      increase in the sequestration of control neutrophils compared with the same cells
      in control rat lungs which was, however, less marked than when inflammatory
      neutrophils were used (34.7 (4.7) fold). The mean (SE) pressure developed on
      filtration of inflammatory neutrophils in vitro through a millipore filter (7.53
      (0.2) cm H2O) was greater than that of peripheral blood neutrophils (1.18 (0.2)
      cm H2O). Increased filtration pressure indicates a decrease in cell deformability
      and suggests that this may be a contributory factor to the increased
      sequestration of inflammatory neutrophils in the pulmonary vasculature.
      CONCLUSIONS: This study shows that there is sequestration of neutrophils in the
      pulmonary vasculature in normal rat lungs which increases in acute lung
      inflammation and when inflammatory neutrophils are injected into control animals.
      In this model changes in the neutrophil, such as cell deformability, may have a
      more important role in inducing increased neutrophil sequestration than the
      inflammatory response in the lungs.

PMID- 7638811
TI  - Prognostic factors influencing the outcome in pneumocystis carinii pneumonia in
      patients with AIDS.
AB  - BACKGROUND: Studies attempting to identify the prognostic factors that influence
      the outcome of Pneumocystis carinii pneumonia (PCP) in patients with AIDS using a
      multivariate analysis are few. In order to identify those prognostic factors
      amenable to medical intervention, univariate and multivariate analyses were
      performed on 102 patients with AIDS suffering a first episode of PCP. METHODS:
      One hundred and two consecutive patients with AIDS (51% drug abusers, 45%
      homosexuals, and 4% with other HIV risk factors) admitted to our institution
      between 1986 and 1989 whose respiratory infection was diagnosed by
      bronchoalveolar lavage were studied prospectively. RESULTS: The overall mortality
      was 28%, rising to 79% in those patients who required mechanical ventilation.
      According to univariate analysis the following variables were related to a poor
      prognosis: age > 35 years; risk factor for HIV infection other than drug abuse;
      and AIDS diagnosis confirmed before 1988; PaO2 < 8 kPa at admission; severe acute
      respiratory failure on admission (PaO2/FIO2 < 20 kPa); mechanical ventilation;
      antibiotic therapy for PCP other than trimethoprim-sulphamethoxazole; multiple
      microbial pulmonary infection; serum lactate dehydrogenase (LDH) > 22.5 mukat/l
      on admission; serum albumin level < 30 g/l. Multivariate analysis showed that
      only mechanical ventilation was independently associated with a poor outcome.
      CONCLUSIONS: The mortality of AIDS patients presenting with a first episode of
      PCP before 1990 was high (28%). The main prognostic factor associated with poor
      outcome was the requirement for mechanical ventilation due to severe acute
      respiratory failure.

PMID- 7638812
TI  - Use of adenosine deaminase as a diagnostic tool for tuberculous pleurisy.
AB  - BACKGROUND: A statistical audit of adenosine deaminase (ADA) in pleural effusions
      was undertaken. METHODS: ADA analysis, cytological and microbiological
      examinations, and differential cell counts were performed on 462 pleural fluid
      samples. RESULTS: ADA activity in tuberculous effusions was higher than in any
      other diagnostic group. At a level of 50 U/l the sensitivity and specificity for
      the identification of tuberculosis was 90% and 89%, respectively. CONCLUSIONS:
      ADA activity remains a useful test in the evaluation of pleural effusions.

PMID- 7638813
TI  - Posterior subcapsular cataract and inhaled corticosteroid therapy.
AB  - BACKGROUND: Although posterior subcapsular cataract complicates both systemic and
      topical corticosteroid therapy, the literature on the effects of inhaled
      corticosteroids is conflicting. METHODS: One hundred and forty children and young
      adults on inhaled corticosteroids were examined by slit lamp ophthalmoscopy after
      pupillary dilatation; 103 had received one or more short courses (< or = 7 days)
      of oral corticosteroids in the management of acute asthmatic attacks and four had
      also received one or more prolonged courses (> or = 4 weeks) of alternate day
      oral corticosteroid therapy. RESULTS: Bilateral posterior subcapsular cataract
      was identified in one girl who had received several prolonged courses of oral
      corticosteroids, but was not identified in any other patient. CONCLUSIONS: There
      is no evidence to support the contention that inhaled corticosteroid therapy on
      its own, or in association with short courses of oral corticosteroid therapy,
      might cause cataracts. Although children receiving long term systemic
      corticosteroid therapy should be screened for cataracts, this is unnecessary in
      children on inhaled corticosteroids alone.

PMID- 7638814
TI  - Inhaled frusemide and exercise-induced bronchoconstriction in children with
      asthma.
AB  - BACKGROUND: Nebulised frusemide has been shown to be protective against
      bronchoconstricting stimuli in adult asthmatic subjects and against cold air
      challenge in children. Animal studies suggest that inhaled frusemide may be more
      effective in the young. METHODS: A double blind placebo, controlled, crossover
      study on the effect on exercise of pretreatment with frusemide (20 mg) from a
      metered dose inhaler via a large volume spacer (Volumatic) was performed in 12
      asthmatic children. Exercise testing consisted of eight minutes of running on a
      treadmill in an environmentally controlled laboratory. RESULTS: Deterioration in
      lung function was less after frusemide than after the placebo exercise tests. The
      mean (95% CI) maximum percentage falls in forced expiratory volume in one second
      (FEV1) were 14.4% (7.7 to 21.0) for placebo and 5.7% (2.3 to 9.0) for frusemide.
      CONCLUSIONS: Inhaled frusemide via a metered dose inhaler reduces exercise
      induced bronchoconstriction in children.

PMID- 7638815
TI  - Salmeterol inhaler using a non-chlorinated propellant, HFA134a: systemic
      pharmacodynamic activity in healthy volunteers.
AB  - BACKGROUND: Metered dose inhalers for the treatment of asthma use
      chlorofluorocarbons as propellants. These face an international ban due to their
      effect on the ozone layer. Salmeterol has been reformulated using the non
      chlorinated propellant Glaxo inhalation grade HFA134a. METHODS: The safety,
      tolerability and systemic pharmacodynamic activity of the salmeterol/HFA134a
      inhaler, the current salmeterol inhaler, and placebo (HFA134a) were compared in
      12 healthy volunteers in a double blind, randomised crossover study using a
      cumulative dosing design. RESULTS: Safety and tolerability were similar and the
      response was related to the dose over the range used (50-400 micrograms) with
      both salmeterol inhalers. The salmeterol/HFA134a inhaler showed no differences
      from the current inhaler for pulse rate, blood pressure, tremor, QTc interval,
      and plasma glucose levels. The salmeterol/HFA134a inhaler had significantly less
      effect on plasma potassium levels. CONCLUSIONS: In healthy volunteers the
      salmeterol/HFA134a inhaler is at least as safe and well tolerated as the current
      salmeterol inhaler, and has similar systemic pharmacodynamic activity.

PMID- 7638816
TI  - Sleep-related breathing disorders. 1. Obstructive sleep apnoea: definitions,
      epidemiology, and natural history.

PMID- 7638817
TI  - Obstructive sleep apnoea with Arnold-Chiari malformation.
AB  - A case of obstructive sleep apnoea associated with the Arnold-Chiari malformation
      is described, in which the loss of pharyngeal sensation seems to have played an
      important part in the aetiology of the obstruction of the upper airway.

PMID- 7638818
TI  - Sleep apnoea syndrome secondary to rheumatoid arthritis.
AB  - A patient who developed severe sleepiness and sleep apnoea in association with
      adult acquired retrognathia and subluxation of the cervical spine at the level of
      C3-C4, both resulting from rheumatoid arthritis, is described. The possible
      causative factors of the association between sleep apnoea and rheumatoid
      arthritis include reduction of the size of the upper airway by temporomandibular
      joint destruction, brainstem compression due to rheumatoid arthritis affecting
      the cervical spine, sleep fragmentation, and drug effects.

PMID- 7638819
TI  - Paradoxical vocal cord adduction in an adolescent with cystic fibrosis.
AB  - Many patients with cystic fibrosis have symptoms of dyspnoea and wheeze which are
      responsive to treatment with bronchodilators. An adolescent woman with cystic
      fibrosis is described who presented with inspiratory stridor and in whom the
      classical features of paradoxical vocal cord adduction were found.

PMID- 7638820
TI  - Dieulafoy's disease of the bronchus.
AB  - Dieulafoy's vascular malformation has not been described outside the
      gastrointestinal tract. Two cases are reported in which this vascular abnormality
      arose in right lower lobe bronchi, both of which presented with massive
      haemoptysis.

PMID- 7638821
TI  - Pulmonary veno-occlusive disease presenting with thrombosis of pulmonary
      arteries.
AB  - Pulmonary veno-occlusive disease is a rare cause of pulmonary hypertension. An
      unusual case presenting with thrombosis of the right pulmonary artery and
      serological evidence of autoimmunity is reported.

PMID- 7638822
TI  - BAL fluid analysis and HIV-1 infection.

PMID- 7638823
TI  - Transfer of severe asthmatics.

PMID- 7638824
TI  - Tuberculosis in the UK, 1994.

PMID- 7638825
TI  - [Muslim physicians in Egypt].

PMID- 7638827
TI  - [Increased governmental steering of health services].

PMID- 7638826
TI  - [We need a Pendleton in social medicine. A task for the new scientific position
      in social medicine?].

PMID- 7638828
TI  - [Peroral fluid therapy in gastroenterites. Time to change routines].

PMID- 7638829
TI  - [Parasuicide in Sor-Trondelag 1989-1992--clinical and psychological
      characteristics].
AB  - The present study is based on interviews with 953 patients (572 females and 381
      males) from the county of Sor-Trondelag who came in contact with the health
      services after a parasuicide during the period 1 October 1988 to 31 December
      1992. Almost half of the patients had a history of earlier parasuicide, and
      almost half reported that the intention of the last parasuicide was to kill
      themselves. The parasuicides were regarded as serious by the medical staff in 26%
      of the cases. There was a significant association between suicidal intention and
      seriousness. The patients often reported alcohol, drug, family and psychiatric
      problems, and had often been in contact with health services during the month
      preceding the parasuicide. 3% of the females and 23% of the males had been
      sentenced to jail. 24% had experienced a parasuicide and 17% a suicide among
      family members or friends. 33% of the females and 18% of the males reported
      having been physically abused, and 14% of the females and 6% of the males
      reported sexual abuse. The results are discussed in light of previous Norwegian
      studies.

PMID- 7638830
TI  - [Percutaneous pyeloplasty of ureteropelvic junction stenoses].
AB  - From March 1990 to November 1993, percutaneous endopyelotomy was performed in 22
      patients for treatment of symptomatic ureteropelvic obstruction. One patient was
      treated bilaterally. In three patients renal pelvic stones were removed during
      the same procedure. Clinical findings, intravenous pyelography and isotope
      renography were considered in preoperative and postoperative evaluation. Overall,
      18 of 23 procedures (79%) were successful. The success rate was lowest in
      patients with enlarged renal pelvis. Failed procedures became evident less than
      six months after operation.

PMID- 7638831
TI  - [Extravasation of cytostatic agents--what is a good treatment?].
AB  - Extravasation of vesicant antitumour agents is a feared complication within
      oncologic therapy. The treatment is often meant to give palliation. Should
      extravasation occur it might further spoil the limited time many of these
      patients have left to live. The question is how to treat an extravasation injury
      without giving the patient an additional problem. The aim must be to remove the
      vesicant as soon as possible in a way that implies minimum morbidity and loss of
      function. At the Norwegian Radium Hospital, oncologists and plastic surgeons have
      cooperated on early surgical intervention, with good results. In our opinion, the
      problem arises when treatment is delayed. We present a retrospective study of 19
      patients operated at the Norwegian Radium Hospital between 1986 and 1994, and
      discuss current methods of treatment.

PMID- 7638832
TI  - [Environmental poisons and the nervous system].
AB  - The neurons are extremely vulnerable to changes in the local chemical
      environment, and the nervous system has therefore been given special priority and
      protection compared with other organ systems. Neurotoxic syndromes may occur when
      these biochemical conditions are disturbed. The brain is particularly vulnerable
      to hypoxia, and exposure to toxins that interfere with the intake, transport and
      utilization of oxygen provoke rapid and major neuronal damage. Compounds crossing
      the blood-brain barrier may induce both general and extremely localized
      neurotoxic effects. Today, dramatic and acute neurotoxic manifestations seldom
      occur in our part of the world. The focus of attention is now directed at the
      consequences of long-term and low-level exposure. This review presents a general
      description of some neurotoxic mechanisms, and the clinical effects of a few
      hazardous substances, ie metals, pesticides, organic solvents.

PMID- 7638833
TI  - [Peroxisome proliferation and possible cancer hazard].
AB  - Approximately 80 chemicals, including hypolipidemic fibrates, have been shown to
      induce peroxisome proliferation in rodent liver. There is a strong concordance
      between this effect and development of liver cancer in rats and mice. There is
      evidence that the peroxisome proliferators induce cancer via a non-genotoxic,
      receptor-mediated mechanism. Both oxidative stress as a consequence of peroxisome
      proliferation and preferential growth of preneoplastic lesions following
      hepatocyte proliferation have been proposed as underlying processes in the
      neoplastic development. Peroxisome proliferation does not seem to occur in human
      liver to any significant extent. Therefore exposure to chemicals with such an
      effect apparently represents little, if any, human carcinogenic hazard.

PMID- 7638834
TI  - [Gastroenteritis in children. Peroral rehydration, intravenous fluid therapy and
      nutrition].
AB  - In pediatrics, oral rehydration treatment is increasingly used in the management
      of gastroenteritis, and based on third world experiences, it is becoming used
      also in hospitals in western countries. In this paper, the advantages,
      limitations and practical use of oral rehydration treatment are discussed.
      Clinical examination of dehydrated children is described, and guidelines are
      given for intravenous fluid treatment. Furthermore, the article reviews modern
      research on the nutritional management of gastroenteritis. The incidence of
      secondary lactose intolerance has been dramatically reduced in recent decades,
      and this necessitates some changes in our traditional nutritional therapy. Rest
      of the bowels, and removal of lactose from the diet are seldom justified.

PMID- 7638835
TI  - [Factor VIII preparation produced by recombinant DNA-technology is approved in
      Norway].
AB  - Recombinant factor VIII (Baxter) is approved by the Norwegian Medicines Control
      Authority. The product represents an alternative to plasma-derived factor VIII in
      the treatment of patients with haemophilia A. Its use should be guided by
      clinical experts in care of haemophilia. Characterization studies of this and
      another recombinant factor VIII preparation have revealed no significant
      differences from plasma-derived factor VIII as regards biochemical and functional
      properties. Clinical studies have demonstrated similar in vivo recovery, plasma
      half-life and haemostatic activity as for plasma-derived factor VIII. Recombinant
      factor VIII should carry a low, if any, risk of transmitting blood-borne viruses
      pathogenic to man. The product includes pasteurized human albumin added as
      stabilizer, which has a well-documented safety record. There is no clear evidence
      of increased incidence of factor VIII inhibitors than with plasma-derived factor
      VIII. Further long-term surveillance studies are needed, however, to elucidate
      these matters.

PMID- 7638836
TI  - [Preventive health practices. What can be learned from municipal accounts?].
AB  - To what extent does health promotion work vary among the municipalities, and how
      can the variation be explained? We answer these questions by analyzing
      municipality accounts for 1991 and 1992. According to these accounts, there is a
      large difference in municipalities' involvement. We seek to explain this
      variation through different hypotheses, and show that part of the variation can
      be explained by the size of the local revenues. Demographic needs and
      organizational aspects seem to have lesser effect. On the other hand, there is a
      clear connection between earmarked grants from central government and the
      municipality's involvement in health promotion. This analysis is unable to
      determine, however, whether earmarked grants are a cause of municipal
      involvement, or an effect of local activity.

PMID- 7638837
TI  - [Consumer participation in the shaping of clinical quality assurance. A handling
      oriented study of patient satisfaction].
AB  - Health care in a department of rheumatology was evaluated by interviewing 15
      patients by a person not associated with the department. The patients' evaluation
      of the health care was then further evaluated by 264 former patients and the
      staff. There was a considerable mismatch between the patients' and staff's rating
      of the problems. The patients' feedback was then used systematically to choose
      between alternative methods of organising and providing the health care, and the
      effect of this was then re-evaluated by the patients.

PMID- 7638838
TI  - [Increased quality demands for emergency internal medicine. Increased resource
      crisis or a possibility for growth through new thinking?].

PMID- 7638839
TI  - [Do we honour those who deserve to be honoured?].

PMID- 7638840
TI  - [A spade is a spade and demagogy is demagogy].

PMID- 7638841
TI  - [Thrombolytic therapy in acute myocardial infarction. Should we start the
      treatment prior the patient's admission to hospital?].

PMID- 7638842
TI  - [Are we able to reduce the use of antibiotics in acute bronchitis?].

PMID- 7638843
TI  - [Compartment pressure after intramedullary fracture nailing].
AB  - Acute compartment syndrome is a serious complication to tibial fractures. The
      reported incidence is 1-10%. The present series includes 60 patients treated with
      intramedullary nailing of fractures in the tibial diaphysis. Tissue pressure was
      measured in 31 patients. Decompressive fasciotomy was performed if the pressure
      exceeded 30 mm Hg for more than 30 minutes. Follow-up showed no patients with
      clinical sequelae from a compartment syndrome, but the incidence of fasciotomy
      was as high as 18%.

PMID- 7638844
TI  - [The hibernating myocardium].
AB  - The hibernating myocardium refers to the presence of persistent myocardial and
      left ventricular dysfunction at rest, due to reduced coronary blood flow. This
      left ventricular dysfunction represents an endogenous adaptive mechanism which
      prevents irreversible cell damage. The dysfunction in hibernating myocardium
      improves following restoration of coronary blood flow. A key concept in
      hibernating myocardium is that the reduction in contractile function induced by
      ischaemia has a protective effect. By reducing oxygen demand the myocardium
      maintains its viability in the setting of limited oxygen supply. The hibernating
      myocardium is a new metabolic state that is a consequence of an ischaemic
      condition, but the hibernating cardiomyocytes are not necessarily ischaemic.
      There are no adequate animal models for chronic hibernation. However, there are
      models for acute hibernation both in intact beating hearts and in isolated
      hearts. In these models a stable reduction in mechanical function for some hours
      has been demonstrated, whereas metabolic indicators of ischaemia improve during
      sustained low-flow ischaemia.

PMID- 7638845
TI  - [Intranasal meningeal cysts].
AB  - Intrasacral meningeal cysts are relatively uncommon. They are usually
      asymptomatic, but because of their expansive character, radicular symptoms or
      functional disturbances in the urinary bladder or rectum can occur. It is of
      importance to recognize these cysts in order to give the patient the correct
      treatment and to avoid unnecessary examinations and operations. The diagnosis can
      be made by myelography, computer tomography or magnetic resonance imaging.

PMID- 7638846
TI  - [Anterior sacral meningocele].
AB  - Anterior sacral meningocele is an uncommon and often occult disorder of clinical
      importance. The pelvic mass induces symptoms mainly because of its pressure on
      surrounding organs. Obstipation and urinary symptoms are common. In females,
      complications due to prolonged or obstructed labour and infections are serious
      and can be fatal. The radiological manifestation is quite typical. It is
      important to be aware of anterior sacral meningocele in order to reach the right
      diagnosis, and to suspect it when typical symptoms are present.

PMID- 7638847
TI  - [Light stylet--an alternative when intubation is difficult].
AB  - Using a light stylet, it is possible to perform oro- and nasotracheal intubation
      without the need of visualizing the larynx or extending the patient's neck. This
      makes the light stylet a valuable alternative when conventional intubation with a
      laryngoscope is difficult or impossible. Intubation with the light stylet is easy
      to learn, is relatively atraumatic, has an acceptable success rate and is fast
      enough to compete with laryngoscopic intubation. The equipment is inexpensive. We
      describe successful intubation with the light stylet in four patients. Two had
      unstable neck fractures, one had previously been difficult to intubate, and one
      had trismus.

PMID- 7638848
TI  - [Clinical neuropsychology].
AB  - The article reviews the development of clinical neuropsychology as a professional
      discipline and comments on important contributions from various research fields
      and clinical disciplines. The consequences of disturbances in the
      neurotransmitter systems for neuropsychological functioning are discussed, as
      well as various clinical issues and the applications of clinical neuropsychology,
      and of neuropsychological evaluations.

PMID- 7638849
TI  - [Neuronal migration disorders. Radiological and clinical aspects].
AB  - Neuronal migration disorders can cause congenital cerebral malformations during
      the third and fourth months of gestation. They are usually classified as agyria,
      pachygyria, schizencephaly, polymicrogyria and heterotopic gray matter. The best
      diagnostic tool for detecting neuronal migration disorders is magnetic resonance
      imaging (MRI). Frequently, the migration disorders are associated with epilepsy,
      psychomotor retardation and cerebral palsy, and patients with these symptoms
      should always be investigated by cerebral MRI. In this article we discuss
      radiologic and clinical aspects in the case of six persons with different
      categories of migration disorders.

PMID- 7638850
TI  - [Blocking of carbohydrate adhesion. A new principle for therapy of many
      conditions?].
AB  - Cell adhesion is of fundamental biological importance. In this article we
      describe the therapeutic potential of blocking carbohydrate dependent adhesion.
      The animal studies are promising, and there is a realistic hope that "anti
      adhesion" therapy for acute conditions like reperfusion injury and severe
      infections will be of clinical value. Treatment of more chronic diseases like
      rheumatoid arthritis and cancer by blocking carbohydrate mediated cell adhesion
      is theoretically possible, but probably more difficult.

PMID- 7638851
TI  - [Prehospital thrombolytic therapy of myocardial infarction in Northern Norway.
      How to improve the service for patients in sparsely-populated areas?].
AB  - Up to now, thrombolytic treatment in myocardial infarction has been restricted to
      coronary care departments in Norwegian hospitals. Owing to the highly significant
      impact of the time elapsing between onset of symptoms and thrombolytic treatment,
      it has been a challenge to offer patients in remote areas early treatment. The
      rescue helicopter in Northern Norway is manned by an anaesthesiologist. By taking
      advantage of this, in combination with strict diagnostic criteria, prehospital
      treatment with streptokinase is now offered in addition to pain relief, oxygen,
      nitrates and aspirin, and observation against arrhythmia. By these means,
      patients in remote areas can receive thrombolytic treatment without the delay
      caused by transportation and in-hospital examination, and a high level of safety
      is maintained. It still remains, however, to shorten the patients' and the
      doctors' delay in notifying the helicopter. It is suggested, that all
      anaesthesiologist-manned air ambulances implement this technique after consulting
      local general practitioners and cardiologists.

PMID- 7638852
TI  - [Investigation of palpable breast tumours. Patient flow and quality assessment of
      the tripple diagnostic procedure].
AB  - The evaluation of patients with a palpable breast lump includes physical
      examination, mammography, and fine needle aspiration cytology. Combined use of
      these diagnostic procedures (triple diagnostic) gives nearly the same degree of
      accuracy as excisional biopsy with a sensitivity of 97-99% in patients with
      palpable breast carcinomas. Ultrasonography is a valuable adjunct when
      mammography is normal or nonconclusive and should be the primary imaging modality
      in patients under 35 years of age with benign findings on physical examination.
      Ongoing quality assessment of mammography and ultrasonography is mandatory, since
      the imaging modalities play a central role in the evaluation of patients with
      lumps in the breast. There are considerable practical problems associated with
      the medical audit of the triple diagnostic procedure. Aspects of the evaluation
      of breast lumps and organization of breast imaging centres are discussed in the
      light of our own experiences.

PMID- 7638853
TI  - [A simple survey of post-traumatic stress disorders among Bosnian war refugees in
      Norway].
AB  - 150 Bosnian war refugees (100 men and 50 women) were followed for 12 months by
      means of a brief screening procedure to determine prevalence and course of
      symptoms of post-traumatic stress disorder. 88 men and 18 women had spent some
      time in Serbian concentration camps before arriving in Norway. A short check list
      for interview and a simple self-assessment questionnaire based on stressor and
      symptom criteria for post-traumatic stress disorders according to DSM-III-R were
      used three times. The number of persons with a diagnosis of post-traumatic stress
      disorder remained high throughout the period of observation. The presented
      diagnostic approach was compared with a comprehensive, standardized diagnostic
      test battery applied in a similar population of refugees by comparing the
      outcomes. For the majority of outcomes, no significant difference in prevalence
      was found. The experiences and results indicate that our approach is practicable,
      and can deliver diagnostic outcomes with acceptable validity.

PMID- 7638854
TI  - [Mesurement errors--concepts and terminology for different specialties].

PMID- 7638855
TI  - [Diagnostic imaging in epilepsy].

PMID- 7638856
TI  - [The 400 year anniversary of pharmacies].

PMID- 7638857
TI  - Genetic polymorphism within HLA-A*02: significant allelic variation revealed in
      different populations.
AB  - HLA-A2 is present at high frequency in most populations, as identified by
      serological and biochemical means. The value of these methods is limited by their
      failure to discriminate between the products of the 14 known allelic HLA-A*02
      variants. The great majority of genetic polymorphism which defines the allelic
      variants is found in exons 2 and 3 of the A*02 genes. These exons encode the
      alpha-1 and alpha-2 domains of the HLA Class I molecules, and variation within
      the genes may influence the peptide binding specificity of the gene products of
      each allele. Failure to accurately assign the allelic types has implications in
      transplantation, in interpretation of cellular assays and in the understanding of
      HLA disease associations. We have developed a method for determining the 14 known
      alleles of HLA-A*02 by use of ARMS-PCR to determine the degree of variation of
      HLA-A*02 alleles in 3 different population groups. Considerable variation was
      found in the relative frequencies of particular A*02 alleles between Caucasian,
      oriental and black individuals. Our results indicate the importance of ethnic
      origin in terms of the expected HLA-A*02 allelic profile, and emphasize the
      functional significance of allele specific subtyping of HLA-A*02.

PMID- 7638858
TI  - Modification of an HLA-B PCR-SSOP typing system leading to improved allele
      determination.
AB  - Modifications have been introduced to a previously reported HLA-B PCR-SSOP typing
      system. This has enabled further definition of alleles, determination of the
      probe pattern of some alleles not previously examined and identification of
      patterns of possible new alleles. However there are still some alleles that
      cannot be differentiated and there are several alleles which when present as a
      homozygote have the same pattern as in combination with another allele. When the
      method was applied to the typing of 66 consecutive cadaveric donors there were
      three donors whose type differed from the serological type.

PMID- 7638859
TI  - The contribution of the HLA-A, -B, -C and -DR, -DQ DNA typing to the study of the
      origins of Spaniards and Basques.
AB  - The high polymorphism of the HLA system has been used as a powerful genetic tool
      to single out individuals and populations. By studying characteristic allele
      frequencies and extended HLA haplotypes in different populations, it is possible
      to identify ethnic groups and establish the genetic relationships among them. In
      the present study, HLA-A, -B, -C, -DR and -DQ typing at the serological/antigenic
      and the DNA level has been used for the first time to assign specific HLA
      frequencies and haplotypes to Spaniards and Basques and compare them with
      frequencies in other populations, particularly with North Africans. Allelic
      frequencies do not significantly differ between Spaniards and Basques. HLA
      genetic distances and their respective dendrogram together with the results on
      complete HLA haplotypes place Basques and Spaniards closer to paleo-North African
      populations than to other Europeans. This goes in favour of the Basques being a
      relative genetic isolate coming from the primitive Iberian/paleo-North African
      people. In addition, a tentative assignment of the most common Spanish HLA
      haplotypes to the different people who populated Iberia according to historical
      records has been done.

PMID- 7638860
TI  - HLA class II typing and idiopathic IgA nephropathy (IgAN): DQB1*0301, a possible
      marker of unfavorable outcome.
AB  - Previous studies have reported associations between HLA antigens and Idiopathic
      IgA Nephropathy (IgAN). Nevertheless most of the studies were performed by
      serology. Thus we decided to perform the HLA class II typing of 58 patients by
      molecular biology techniques. We report a small increase of DRB1*04. But the main
      result of our study is the identification of a strong association between HLA
      DQB1*0301 and IgAN patients with an unfavorable outcome.

PMID- 7638861
TI  - Characterization and epitope mapping of four HLA class II reactive mouse
      monoclonal antibodies using transfected L cells and human cells transfected with
      mutants of DQB1*0302.
AB  - To study epitopes of HLA class II molecules, four mouse monoclonal antibodies
      (mAbs) 13B6, 17F8, 19A1 and 12G6 were made using HLA-DQ8, DP2 and DP4 expressing
      mouse transfectants for immunization. Three of the mAbs, 13B6, 17F8 and 19A1,
      bound to all DQ1, 4, 8 or 9 positive B-lymphoblastoid cell lines (B-LCLs) and
      transfectants tested, i.e. cells carrying the DQB1 genes 0302-3, 0401-2, 0501-3,
      0601-4 and 0609 irrespective of the accompanying DQA1 gene. These DQB1 genes code
      for the shared amino acids (aa) GVY in position 45-47 of the DQ beta chain.
      DQ1+4+8+9 specific (IIB3) and DQ3 specific (IVD12) reference mAbs inhibited
      binding of all three mAbs. Testing 13B6, 17F8 and 19A1 with cells made using aa
      substitutions in various positions of DQ beta 1*0302 indicated involvement of aa
      45 in the epitopes of all three mAbs. The last mAb (12G6) bound to all B-LCLs and
      all DP transfected cells. However, only some DR transfectants and a single DQ
      transfectant (carrying DQA1*0201 and DQB1*0202) bound mAb 12G6. This reactivity
      pattern correlates with a shared sequence of aa (RFDSDVGE) in position 39-46 of
      DR- and DQ- and 37-44 of DP beta chains.

PMID- 7638862
TI  - Polymorphism in the upstream regulatory region of DQA1 gene in the Italian
      population.
AB  - Polymorphism in the 5'-upstream regulatory region of the DQA1 gene has been
      recently described. Using PCR-SSO method and SSCP analysis we have investigated
      this polymorphism in a group of 111 Italian blood donors which had been
      oligotyped for DRB1, DQA1 and DQB1 genes. Eight allelic variants were detected.
      Looking at the relationships among QAP sequences and DQA1 and DRB1 genes, three
      alternative situations were found: 1. a one-to-one relation between QAP and DQA1
      alleles, independently of the other class II genes; 2. the same QAP allele in
      association with different DQA1-DRB1 haplotypes; 3. the same DQA1 allele with
      different QAP sequences according to the DRB1 specificity. No unexpected
      associations with DQB1 gene were found. These results must be interpreted
      considering that DQA1 and DRB1 genes are transcribed in opposite directions so
      that the promoter region of DQA1 gene lies between DQA1 and DRB1, close to the
      former but several hundreds kb away from the latter.

PMID- 7638863
TI  - HLA-DPB1 alleles in a population from north India and description of a new
      variant (DPB1*5601).
AB  - HLA-DPB1 alleles were studied in 51 normal individuals and 93 leprosy patients
      from North India using a PCR-oligotyping technique. Hybridization patterns could
      identify 47 alleles of which 20 were found in the population studied. DPB1*0401
      was found to be the most frequent allele with a frequency of 66.7% followed by
      DPB1*0402 (21.6%), DPB1*0201 (21.6%), DPB1*1301 (15.7%) and DPB1*0301 (13.7%).
      Besides the common alleles, DPB1*0101, *1701, *2601, *1001, *1601, *0901, *2901,
      *1501, *0501, *1401, and *3301 were observed at low frequencies. DPB1*2101,
      DPB1*2801, DPB1*3201 and DPB1*3501 were not found in the normal individuals
      studied but were observed in the group of leprosy patients. DPB1*0202, *0601,
      *0801 and *1101 were not found in this population. Two alleles with apparent new
      hybridization patterns were isolated and sequenced. The nucleotide sequences
      obtained have confirmed the hybridization patterns. One of them (DPB1*4601)
      confirms a sequence recently reported. The other has been given the official
      designation of DPB1*5601.

PMID- 7638864
TI  - DR4Dw4/DR53 molecules contain a peptide from the autoantigen calreticulin.
AB  - Rheumatoid arthritis (RA) occurs more frequently in HLA-DR4+ individuals than in
      those who do not express this MHC class II molecule. Although the role of this
      genetic factor in the immunopathology of this autoimmune disease is unclear, the
      association of RA with HLA-DR4 may indicate that DR4 molecules present
      autoantigen(s) to T cells. Here we report the analysis of naturally processed
      peptides, eluted from a mixture of HLA-DR4Dw4 (DRB1*0401) and DR53 (DRB4*0101)
      molecules isolated from an RA patient-derived EBV-transformed B cell line.
      Several (size variants of) self-peptides originating from the autologous
      molecules HLA-A2, HLA-Cw9, HLA-B62, HLA-DR4Dw4 and HLA-DR53, were identified. We
      also found a sequence that has no homology to any protein in the SwissProt
      protein sequence databank, and a peptide identical to an internal fragment of the
      autoantigen calreticulin. The association of the identified peptides with cells
      expressing HLA-DR4Dw4/DR53 was confirmed by peptide binding analysis. In
      agreement with previously described peptide binding motifs for DR4Dw4, most
      peptides contained an aromatic residue (Phe, Tyr, Trp) at relative position i and
      a small hydroxyl-containing residue (Ser, Thr) at i + 5. Our findings indicate
      that in RA patient-derived EBV-transformed B cells DR4Dw4/DR53 molecules present
      a peptide from the autoantigen calreticulin. Interestingly, autoantibodies
      against calreticulin have been found in various rheumatic diseases, including
      rheumatoid arthritis. Thus, the analysis of HLA class II-bound peptides can lead
      to the identification of putative T helper epitopes, which might be involved in
      the immunopathology of autoimmune diseases.

PMID- 7638865
TI  - A new member of the HLA-B40 family of alleles, B*4007, coding for B'FU'
      serological specificity.

PMID- 7638866
TI  - Immunogenetics of juvenile chronic arthritis. I. HLA interaction between A2,
      DR5/8-DR/DQ, and DPB1*0201 is a general feature of all subsets of early onset
      pauciarticular juvenile chronic arthritis II. DPB1 polymorphism plays a role in
      systemic juvenile chronic arthritis.

PMID- 7638867
TI  - Nucleotide sequence and polymorphism analysis of canine DRA cDNA clones.

PMID- 7638869
TI  - 11th World Congress on Animal, Plant and Microbial Toxins. Tel Aviv, Israel, 2-7
      October 1994. Abstracts.

PMID- 7638868
TI  - Nomenclature for factors of the HLA system, update February 1995. The WHO
      Nomenclature Committee for Factors of the HLA System.

PMID- 7638870
TI  - Experimental assessment of a new, low-cost antivenom for treatment of carpet
      viper (Echis ocellatus) envenoming.
AB  - Morbidity and mortality due to envenoming by the carpet viper (Echis ocellatus)
      in northern Nigeria remains unacceptably high and constitutes a severe economic
      and public health problem to the local farming community in particular. The only
      effective treatment of systemic envenoming is antivenom, but supplies are very
      limited as the little that is available is either too expensive, ineffective or
      both. Here, we describe a new ovine antivenom, designed both to be effective and
      to be available at low cost. The antivenom, a polyclonal ovine Fab preparation,
      provides superior protection, both in vivo and in vitro, to the best
      alternatives, the monospecific South African Institute of Medical Research
      antivenom and the polyspecific Pasteur Isper Africa antivenom. Fab fragments,
      which have the advantages of large volumes of distribution and, theoretically,
      low immuno-reactivity, are produced by a reusable solid-phase papain matrix which
      eliminates enzyme contamination of the product and reduces cost. The antivenom is
      lyophilised for increased stability and extended shelf-life in tropical climates
      where it is often impossible to keep such products cool.

PMID- 7638871
TI  - Lipid peroxidation in rats intoxicated with 3-nitropropionic acid.
AB  - Using an electron spin resonance technique, free radical signals were observed to
      be increased in liver of rats 15, 30 and 45 min after orally dosing with 80 mg/kg
      3-nitropropionic acid (3-NPA). Concentrations of 3-NPA from 595 to 2380 mg/litre
      enhanced the formation of adrenochrome from adrenaline in mitochondria and
      microsome suspensions of liver and brain. The activities of superoxide dismutase
      (SOD) and glutathione peroxidase (GSH-PX) as well as the content of
      malonidialdehyde (MDA) were significantly increased in liver of rats dosed with
      80 mg/kg 3-NPA. There was also a cerebral increase of activity of SOD and content
      of MDA. These results suggest that 3-NPA is able to produce lipid peroxidation
      both in vivo and in vitro.

PMID- 7638872
TI  - Presence of curarizing polypeptides and a pancreatitis-inducing fraction without
      muscarinic effects in the venom of the Venezuelan scorpion Tityus discrepans
      (Karsch).
AB  - Four toxic polypeptidic fractions (TdF-I-IV) were purified from the venom of the
      Venezuelan scorpion Tityus discrepans by means of gel filtration on Sephadex G'
      50. The peptides have mol. wts of approx. 6000 and normalized elution volumes (Vn
      = Elution volume/Total column volume) of: TdF-I = 0.27 (0.26, 0.28), n = 13; TdF
      II = 0.40 (0.39, 0.41), n = 15; TdF-III = 0.57 (0.56, 0.59), n = 14, and TdF-IV =
      0.68 (0.67, 0.70), n = 13 (median and its 95% confidence interval, n = number of
      elutions used to calculate the median). Mice (white, male, 16-19 g, IVIC strain)
      were injected with these fractions and sacrificed 48 hr later. No toxicity was
      observed when fraction I (0.93 microgram/g mice) or IV (2.51 micrograms/g mice)
      was injected i.p. into mice. TdF-II (9 to 50 micrograms/g mice) produced
      sialorrhea, dyspnea and death 1 hr after i.p. injection. Light microscopy of the
      pancreas revealed that TdF-III (3.42 micrograms/g mice) produced structural
      modifications such as acinar cell vacuolization, degranulation and interstitial
      swelling; these changes are characteristic of acute pancreatitis. No effects on
      the islets of Langerhans or the pancreatic ducts were observed. TdF-III had no
      overt muscarinic effects when injected i.p. into mice. On the neuromuscular
      preparation of the frog (Hyla crepitans) TdF-I blocked neuromuscular transmission
      at the postsynaptic membrane; TdF-II depolarized the muscle membrane by opening
      sodium channels and TdF-IV prolonged action potentials, suggesting potassium
      channel blockage.

PMID- 7638873
TI  - Haemocyte changes in the Pacific oyster, Crassostrea gigas, caused by exposure to
      domoic acid in the diatom Pseudonitzschia pungens f. multiseries.
AB  - The physiological effects of domoic acid on the immune system of marine
      invertebrates, which are known to accumulate this neurotoxin, have not been
      investigated previously. Changes in the number and relative phagocytic activity
      of circulating haemocytes in Crassostrea gigas exposed to domoic acid in the
      diatom Pseudonitzschia pungens f. multiseries for 48 hr, followed by clearance
      for 240 hr, were investigated using chemiluminescence. An initial stress response
      to the toxin assimilation was characterized by a marked increase in number and
      activity of haemocytes with 4 hr of exposure to the algae. Although the toxin
      level in the oyster increased during the 48 hr exposure, both number and activity
      of haemocytes declined from the 4 hr peak values to those significantly lower
      than control values after 24 hr clearance. This suppression in number and
      activity of circulating haemocytes following the initial toxin response was
      rectified only after 48 hr clearance, when domoic acid levels in the oyster
      tissue had declined to trace levels, allowing blood cells to regain their normal
      characteristics.

PMID- 7638874
TI  - Effect of scorpion toxin from Tityus serrulatus on the contraction of the
      isolated rat uterus.
AB  - Scorpion toxin T1 from Tityus serrulatus was tested for its effects on the
      isolated rat uterus preparation. T1 (5 micrograms/ml) caused a contraction of the
      uterus, which was potentiated by neostigmine (1.64 x 10(-6) M) and abolished by
      atropine (1.4 x 10(-7) M). After addition of neostigmine to the bath, we noted a
      higher amplitude of the toxin-induced contractions, and the appearance of
      repetitive rhythmic contractions. The scorpion toxin-induced contraction was not
      prevented by previous addition to the bath of hexamethonium or bradykinin, 5-HT
      and angiotensin II antagonists. The uterine contraction was prevented by previous
      addition to the bath of either tetrodotoxin (5 x 10(-8) M) or lidocaine (4.2 x
      10(-5) M). These data seem to indicate that scorpion toxin-induced rat uterus
      contractions are due to actions on post-ganglionic autonomic nerve endings, with
      acetylcholine release and stimulation of muscarinic receptors.

PMID- 7638875
TI  - Effects of waglerin-I on neuromuscular transmission of mouse nerve-muscle
      preparations.
AB  - The effects of waglerin-I, a toxin from Trimeresurus wagleri, on neuromuscular
      (NM) transmission were studied on the phrenic nerve-diaphragm preparation and
      triangularis sterni nerve-muscle preparation of mice. The toxin (1.2-4.0 microM)
      reversibly inhibited the indirectly elicited twitch tension of the diaphragm and
      decreased the ACh-elicited muscle contracture of chronically denervated
      diaphragm, while the directly elicited twitch tension was not affected. The toxin
      reversibly decreased the amplitude of miniature endplate potential (MEPP) at 0.52
      microM and endplate potential (EPP) at 1.2-4 nM. The toxin (120 nM-0.4 microM)
      also decreased the quantal content of EPP. The perineural waveforms were recorded
      with an extracellular electrode placed into the perineural sheaths of motor
      nerves of M. triangularis sterni. The toxin (4 microM) did not alter the
      amplitudes of waveforms related to sodium and potassium currents of the nerve
      terminal action potential, while the waveform related to calcium current was
      decreased. It is concluded that the toxin acts on both presynaptic and
      postsynaptic sites of the mouse motor endplate, and that the presynaptic effect
      is apparently more potent than the postsynaptic effect.

PMID- 7638876
TI  - Humoral response following Russell's viper (Daboia russelli siamensis) bites in
      Myanmar.
AB  - A prospective study of the development, intensity and protective ability of the
      antibody response to Russell's viper bite and its relation to the severity of
      envenoming was carried out in 15 patients 3 to 116 weeks after the bites using
      enzyme immunoassay. Retrospective screening in 123 cases revealed antibody in
      112/123 (91%) which could be detected from 1 week to 15 years after the bite. A
      slow peaking (30 weeks) and waning of antibody response was observed in the
      majority of cases. Development of antibody response was related to the initial
      venom level, rather than to the delay between bite and antivenom therapy, or the
      dose of antivenom. Uraemia depressed the IgM response to venom.

PMID- 7638877
TI  - King cobra (Ophiophagus hannah) bites in Myanmar: venom antigen levels and
      development of venom antibodies.
AB  - Venom, venom IgG and IgM antibody and total serum IgG levels following king cobra
      bites in two reptile handlers were measured by enzyme immunoassay. The patient in
      case 1 received antivenom while the patient in case 2 did not. Case 1 made a
      complete recovery following the bite and produced a high titre short-lived
      antibody. Venom antigen was not detected in the sample taken 11 hr after
      antivenom. Case 2 had experienced two recent minor king cobra bites and had
      received traditional immunization 4 weeks before the accident reported here. He
      had developed only local swelling and suffered no neurological symptoms. Venom
      antigen measured at 1.45 hr after the bite was 132 ng/ml; this rapidly fell to 45
      ng/ml over the next 30 min, and was no longer detectable 14 hr after the bite.
      The pattern of venom IgG and IgM antibody responses in both cases was comparable,
      except that in case 2 the venom IgG peak was maintained for 13 days, compared
      with 1 day in case 1; in case 2 it subsequently fell to low levels 8 weeks after
      the bite. Venom IgM appeared 1 day after the bite, peaked at day 7-9, rapidly
      tailed off on day 12-16 and was then undetectable from day 20 onwards in both.
      Total IgG level remained within normal limits in both. It is possible that
      previous bites and recent immunization contributed to the boosting of the venom
      IgG response in case 2.

PMID- 7638878
TI  - Crystallization and preliminary diffraction data of bothropstoxin I isolated from
      the venom of Bothrops jararacussu.
AB  - The myotoxic Lys-49 phospholipase bothropstoxin I was crystallized, and X-ray
      diffraction data were collected to 3.5 A resolution. Preliminary analysis reveals
      the presence of four molecules in the asymmetric unit.

PMID- 7638879
TI  - Bibliography of toxinology.

PMID- 7638880
TI  - [The forensic medical assessment of light bodily injuries. 2].

PMID- 7638881
TI  - [The characteristics of diagnosing homosexuality in examining a special
      population contingent].
AB  - In social terms homosexuality is one of the most dangerous sexual perversions,
      for it is subject to a strong social disapproval, affects the personality core,
      leads to social disadaptation, growth of anxiety, development of neurotic and
      depressive states, suicidal inclination, is conducive to the spread of syphilis
      and AIDS, forms the basis for numerous crimes (violence, aggression, murder).
      Homosexuality virtually cannot be corrected and is carefully concealed. In single
      sex groups (soldiers, students of military schools, convicts) the prevalence of
      homosexuality may be as high as 30 to 50%. The proposed complex method for the
      diagnosis of homosexuality in men has been developed on the basis of methods of
      sexology, anthropometry, verbal and nonverbal psychodiagnosis, multidimensional
      mathematical statistics. The method consists of several independent blocks
      representing different aspects of sexuality. It is conductive to a flexible and
      rapid solution of numerous practical problems from singling out a risk group in
      screening examinations to full expert evaluation of the sexual sphere with a
      resulting differential diagnosis.

PMID- 7638882
TI  - [The use of capillaroscopy of the skin of the nail wall in personal
      identification].
AB  - Capillaries of the nail wall skin are the most convenient objects for
      investigation in a live man. Over 2500 investigations were carried out, which
      demonstrated, that, despite a marked variability of morphometric parameters, the
      contour of capillary loops on each subject is individual, this recommending
      capillaroscopy of the skin as a method for personality identification.

PMID- 7638883
TI  - [The morphological signs of hair disease in children poisoned by thallium and
      boron].
AB  - Morphologic signs of hair disease of children aged 1 to 5 (town of Chernovtsy,
      Ukraine) with poisoning are presented. Using scanning electron and light
      microscopy revealed a number of morphologic signs in the radicular part and bulbs
      of hairs, which are commonly observed in thallium poisoning.

PMID- 7638884
TI  - [The determination of ferroceron in the practice of forensic chemical expertise].
AB  - Valov's method followed by extraction of the acid form of ferroceron with ether
      is recommended for isolation of ferroceron from cadaveric material in forensic
      chemical practice expert evaluation. Detection and measurement of isolated
      ferroceron are carried out by thin-layer chromatography and spectroscopy in the
      visible part of the spectrum. The developed method for ferroceron detection in
      cadaveric material was used in two expert evaluations. Recommendations are
      offered on the detection of ferroceron in cadaveric and biological material and
      on resuscitation measures in cases with poisoning with this drug.

PMID- 7638885
TI  - [The competence of persons who abuse alcohol when they complete property
      transactions].
AB  - Changes in the social conditions and attitude to property led to a drastic
      increase of the number of property deals and of expert evaluations of the
      competence of subjects committing such deals. Subjects with mental disorders,
      with chronic alcoholism, among other things, frequently participate in such
      deals. It is this population that so often becomes the victim of dealers and is
      left without flats. The authors discuss new interesting questions related to
      difficulties in assessment of the mental status of a chronic alcoholic at the
      moment of commitment of a property deal.

PMID- 7638886
TI  - [Approaches to shaping the modern technologies of producing expertise and to
      regulating the expert process].
AB  - The author proposes transfer to new technology of expert evaluations and of
      management of the forensic medical service of a region. This will appreciably
      improve the quality of expert assessment, accelerate it, and improve labor
      productivity.

PMID- 7638887
TI  - [Erdheim's disease as a cause of sudden death].
AB  - Morphologic findings in three cases are presented. Death was caused by Erdheim's
      disease which was complicated by rupture of a false aneurysm of the ascending
      part of the aorta. A typical dystrophic involvement of the aortic wall at late
      stages of the disease is shown to be associated with a manifest inflammatory
      process presenting as nonspecific aortoarteritis. To verify the diagnosis,
      histologic examination of the aortic wall at some distance from the site of
      rupture should be performed.

PMID- 7638888
TI  - [The Vitus Bering we do not know].

PMID- 7638889
TI  - [The personnel of the forensic chemistry departments of bureaus of forensic
      medical expertise. 2].

PMID- 7638890
TI  - [Personal identification by bone remains in the laboratory of the U.S. Army].

PMID- 7638891
TI  - [The forensic medical service in Australia (exemplified by the state of
      Victoria)].

PMID- 7638892
TI  - [Prof. Nikolai Vladimirovich Popov (on the centenary of his birth)].

PMID- 7638893
TI  - [The 70th anniversary of the Department of Forensic Medicine of the Saint
      Petersburg Medical Academy of Postgraduate Education].

PMID- 7638894
TI  - [The diagnosis of retroperitoneal hematomas].
AB  - The authors developed a method for assessment of the volume of retroperitoneal
      hematomas in children, based on measurements and mathematical processing of two
      parameters (body length or mass and the level of hematoma in relation to the
      lumbar spine). This method may be useful both in forensic and clinical medicine.

PMID- 7638895
TI  - A role for phosphorylation and degradation in the control of NF-kappa B activity.

PMID- 7638896
TI  - The synaptonemal complex and the distribution of meiotic recombination events.

PMID- 7638897
TI  - Transcriptional regulation by a cyclin-cdk.

PMID- 7638898
TI  - Human mitochondria: distinct organelles or dynamic network?

PMID- 7638899
TI  - Opinions on left-right axis formation.

PMID- 7638900
TI  - Opinions on left-right axis formation.

PMID- 7638901
TI  - A simple procedure to increase efficiency of DEAE-dextran transfection of COS
      cells.

PMID- 7638902
TI  - A versatile quick-prep of genomic DNA from gram-positive bacteria.

PMID- 7638903
TI  - Identification of mammalian cell clones exhibiting highly regulated expression
      from inducible promoters.

PMID- 7638904
TI  - World Wide Web resources for the biologist.
AB  - The World Wide Web is currently the major networking resource for biologists. It
      has passed Gopher and simple electronic mail (email) servers in popularity. In
      the 1990s, the advent of client-server software will be the main driving force in
      bioinformatics. During the past few years, biologists have used the Internet
      increasingly to distribute data, and the methods of doing this have become more
      and more sophisticated as the speed with which network links can be made has
      increased.

PMID- 7638905
TI  - The maize mitochondrial genome: dynamic, yet functional.
AB  - The organization of the mitochondrial genome of higher plants is complex. It has
      two striking features: a large size that can vary among plant species; and the
      ability to undergo homologous recombination that results in variation within
      species. From cosmid clone mapping studies, the total genetic information of the
      plant mitochondrial genome can be arranged into a single circular molecule that
      is referred to as the master chromosome. This circular DNA molecule contains
      repeated sequences that can generate, via intramolecular recombination, either
      isomeric forms of the master chromosome or smaller subgenomic circular DNA
      molecules. The maize mitochondrial genome is the most complex and largest
      mitochondrial genome for which a physical map is presently available. Its
      organization varies considerably among the different maize cytotypes. In an
      attempt to understand the numerous different mitochondrial DNA rearrangements
      encountered among those cytotypes, we have proposed a general model of genome
      evolution that can explain a multitude of genomic rearrangements, not only for
      the maize mitochondrial DNA but also for other higher plant mitochondrial genomes
      as well.

PMID- 7638907
TI  - [Rehabilitation after fractures--why? how?].

PMID- 7638906
TI  - Genetic approaches to nuclear pore structure and function.
AB  - The major features of nucleocytoplasmic transport through nuclear pore complexes
      are conserved from yeast to humans. This transport machinery, which includes the
      125 MDa nuclear pore complex structure, has been molecularly dissected in the
      yeast Saccharomyces cerevisiae by genetic approaches. Here, we summarize the
      genetic analyses used to elucidate structure-function relationships within this
      large supramolecular assembly.

PMID- 7638908
TI  - [Rehabilitation after trochanteric femoral fractures].
AB  - Hip fractures constitute an increasing problem due to the associated lengthy
      hospitalization, pressure on orthopaedic units and the frequently serious
      consequences for the health and social function of the patients. The outcome of
      rehabilitation following hip fractures depends on several prefracture risk
      factors with only limited possibilities for intervention. Modern surgical
      techniques permit early mobilisation and possible changes in surgical procedures
      will probably not essentially influence the outcome of rehabilitation. Foreign
      experiences, however, suggest that early transfer to a specialized unit for
      rehabilitative aftercare involves more effective rehabilitation with reduced
      consumption of resources.

PMID- 7638909
TI  - [Marginal costs of total hip replacement--experiences from a county hospital
      department].
AB  - The marginal cost of total hip replacement was analysed at a county hospital in
      Denmark. We found that, with correction for inflation the price of a hip
      prosthesis has remained stable. In addition, we found that the cost of total hip
      replacement at a public hospital is considerably lower than the price listed at
      private hospitals in Denmark. We therefore conclude, that from an economic
      viewpoint it would be better to expand the existing capacity at public hospitals
      than that the public health service should pay for treatment of patients at
      private hospitals.

PMID- 7638910
TI  - [Laparoscopic surgery].

PMID- 7638911
TI  - [Laparoscopic ultrasonography. A review and authors' own experiences].
AB  - Laparoscopic ultrasound scanning has long been available, but interest in and
      reports of the technique have until the last few years been sporadic. The rapid
      development and growing interest in laparoscopic surgery as well as the advent of
      commercially available systems designed for laparoscopic ultrasound have resulted
      in renewed interest in the technique. The available published reports lack
      prospective, controlled clinical studies with respect to where and when
      laparoscopic ultrasound would be indicated. A favourable picture is given as
      concerns the use of laparoscopic ultrasound in the diagnosis and evaluation of
      primary liver and pancreas tumours as well as liver metastases. Laparoscopic
      ultrasound is also mentioned as a reliable alternative to cholangiography in
      laparoscopic cholecystectomy. Our own preliminary experiences with two
      laparoscopic ultrasound systems and a simple system using an ultrasound finger
      probe are described. A laparoscopic ultrasound scanning system consisting of a
      stiff instrument with a convex (linear) transducer mounted on a flexible support
      and with the possibility of ultrasound-guided biopsy and colour-Doppler seems
      optimal. Prospective studies are being carried out to identify areas of
      utilization and limitations of laparoscopic ultrasound.

PMID- 7638912
TI  - [Laparoscopic ultrasonography of liver, biliary tract and pancreas with flexible
      tip transducers].
AB  - The scanning procedure and the ultrasound-anatomy of the liver, gall-bladder,
      bile ducts and pancreas are presented. Ten consecutive patients referred for
      laparoscopic cholecystectomy were scanned through a 10/11 mm trocar inserted
      periumbilically. In two cases concrements in the bile ducts were found
      peroperatively. The flexible-tip enables operator steering of the transducer
      which ensures an optimal acoustic contact. Colour and spectral Doppler were
      frequently used to identify vascular structures. We conclude that a flexible-tip
      laparoscopic ultrasound-scanner provides valuable assistance in abdominal
      laparoscopic procedures, and may substitute the palpation of the abdominal organs
      in laparoscopic abdominal surgery.

PMID- 7638913
TI  - [Randomized trial on the value of diagnostic laparoscopy before appendectomy].
AB  - Two groups of 30 women with clinical signs of appendicitis were randomized to
      immediate appendicectomy or diagnostic laparoscopy. In the latter group,
      appendicectomy was performed if a diagnosis of acute appendicitis was established
      or if the appendix could not be visualized. Eleven patients who underwent
      immediate operation had unnecessary appendicectomy, compared with two who
      underwent laparoscopy. This difference of 30% (95% confidence interval 11-49%)
      was significant (p = 0.01). There was no significant difference in postoperative
      morbidity rate in the two groups. Diagnostic laparoscopy is a useful preliminary
      investigation in women with clinical signs of acute appendicitis.

PMID- 7638914
TI  - [Legionella pneumophila in the hot water system of Danish hospitals and
      institutions. A questionnaire study and a random sample test].
AB  - Hitherto, nosocomial epidemic outbreaks of legionnaire's disease have not been
      reported in Denmark. Only sporadic cases have been described. A survey of 75
      Danish hospitals concerning the dimensions and operation of the hot-water systems
      revealed that only 13% had a hot water tank temperature above the recommended 60
      degrees C. Temperatures of coldest tap water and of returning water were above 50
      degrees C in only 31% and 24% respectively. Twelve representative hospitals with
      35 independent water systems were investigated for the presence of Legionella
      pneumophila (Lp). Lp was demonstrated in all the hospitals and in 34 (97%) of the
      systems. The prevailing serogroups were (in order of frequency) 3, 1, 2, 5 and 6.
      We conclude that the operation of the hot tap water systems should be optimized.
      This report indicates that nosocomial epidemics are conceivable and attention
      should be paid to the disease as a diagnostic possibility in patients with
      primary atypical pneumonia.

PMID- 7638916
TI  - [Digital strangulation--released by the use of a dentist's drill].
AB  - A six year-old girl got her third right finger stuck into a padlock-fitting made
      of hardened steel. It was impossible to loosen the finger using the conventional
      methods of oil, soap, cooling, compression or wind-unwind technique. The fitting
      was split using a dentist's high speed drill and then easily removed leaving the
      finger uninjured.

PMID- 7638915
TI  - [Nosocomial Legionella pneumophila infection in a nephrology department].
AB  - During the autumn and winter of 1993-94 four cases of legionellosis were
      diagnosed in a Department of Nephrology. Three of the patients were kidney
      transplanted patients. Two of the patients died. The diagnosis was based on
      positive culture in two patients and by positive urinary antigen test in the
      other two patients. Serology was negative for all four patients. Legionella
      pneumophila was initially found in the cold and hot shower water, in ice-water
      from the ice machine, from the hot water tank and in the cold water inlet to the
      building. The isolate from patient no. one and isolates of serogroup 5 from the
      ice machine and the shower water had identical REA profiles, different from the
      profiles of the isolate from patient no. four. We concluded that at least one of
      the four patients was likely to have been infected from the water in the
      department, either by inhalation of contaminated aerosols from the shower or by
      aspiration of contaminated ice-water. Precautions were taken to reduce the number
      of Legionella in the shower- and ice-water. In addition, restrictions in the use
      of showers and ice-water from the ice machine were introduced.

PMID- 7638917
TI  - [Severe vitamin D deficiency in an immigrant family].
AB  - A case of severe vitamin D deficiency in a family of immigrants is presented. All
      had secondary hyperparathyroidism and the children had hypocalcaemia. Symptoms
      and pathogenesis including dark skin pigmentation and vegetarianism are
      discussed. It is recommended that the whole family be screened if a deficiency of
      vitamin D caused by skin pigmentation or eating habits is found in one of the
      family members.

PMID- 7638918
TI  - [Reliability of controlled clinical trials--the problem of randomization].

PMID- 7638919
TI  - [Guidelines for documentation of data].

PMID- 7638920
TI  - [Recurrent abdominal pain in children and Helicobacter pylori].

PMID- 7638921
TI  - [Organizational strategy for the treatment of apoplexy?].

PMID- 7638922
TI  - [Ultrasound criteria of fresh rupture of the anterior cruciate ligament].
AB  - In a prospective, controlled, monocentric clinical study 193 recently traumatized
      knee joints, suspicious of a ruptured anterior cruciate ligament, were examined
      sonographically. Three indirect signs of rupture were analyzed and compared to
      the results of the clinical tests of stability (Lachmann). Arthroscopy and
      arthrotomy were regarded as approved methods of reference. The sonographic
      pattern of an echo-free mass in the area of the femoral insertion of the anterior
      cruciate ligament proved to be more informative (sensitivity 0.91, specificity
      0.78, effectivity 0.84) than the clinical signs of instability. A standardized
      sonographic examination of the knee joint should be a constant component of the
      posttraumatic examination. It is an inexpensive method, easy to learn and to
      perform, and is more reliable in the diagnosis of the ruptured anterior cruciate
      ligament than the clinical evaluation of instability.

PMID- 7638923
TI  - [Examinations with the KT-1000 knee arthrometer in injuries of the posterior
      cruciate ligament in comparison with stress roentgen images in the Scheuba
      positioning device].
AB  - Eighteen patients with surgically treated ruptures of the posterior cruciate
      ligament were tested on follow-up 2 to 13 years with KT-1000 Kneearthrometer and
      radiologically according to Scheuba to objectify the clinical results and to
      compare the 2 methods. It could be shown that both methods are highly specific
      and do correspond in 89%. In 11% a borderline difference between a "+" posterior
      drawer and a "++" posterior drawer in the classification by Hughston et al. [5]
      was detected. Since the Scheuba test does involve radiation, the KT-1000 Knee
      arthrometer testing device represents a safe alternative to objectify a posterior
      drawer.

PMID- 7638924
TI  - [Diagnostic possibilities and treatment approaches for fracture of the of the
      intercondylar eminence in the growth period].
AB  - Between 1970 and 1993 29 fractures of the intercondylar eminence were seen in
      children with almost the same number of cases showing no or minor displacement as
      those requiring open reduction for major dislocation. Combined knee injury must
      be suspected the higher the patient's age and the more pronounced the
      displacement of the fragment. Magnetic resonance imaging (MRI) has gained
      diagnostic predominance. Arthroscopy remains important for surgical management,
      especially of associated meniscus and cartilage damage. Early puncture of
      hemarthrosis is essential. Closed management is the therapy for nondisplaced
      fragments or those with bone contact or only tuberculum fractures--while
      displaced fragments require operative reduction. Arthroscopy-aided wire fixation
      is the preferred technique, followed by open reduction using absorbable suture
      material (wire in special cases). Traction screws should be used only in older
      children with large fragments. Our series show good late results because
      occasional function impairment with knee instability tends to normalize with
      growth. Corrective orthopedic procedures--if at all--are required only for
      juveniles or adults.

PMID- 7638925
TI  - [Color-coded duplex ultrasound as a screening method in trauma surgery].
AB  - Deep vein thrombosis with consecutive pulmonary embolism is one of the most
      important complications for trauma patients. At the University Hospital of Mainz,
      Department of Traumatology, colour duplex ultrasound is used as screening method
      in trauma patients. Fractures of thoracic and lumbal spinal bones, pelvis, hip
      and lower extremities, endoprosthesis of hip and knee joints and longer
      immobilisation are considered as special risk for the genesis of deep vein
      thrombosis. Out of 326 patients investigated with colour duplex ultrasound, 24
      patients suffered from unknown deep vein thrombosis, 8 developing pulmonary
      embolism. We recommend colour duplex sonography on day 10, after the third week,
      and after longer immobilisation. Colour duplex sonography provides an easy
      performable and noninvasive method for screening evaluation of deep vein
      thrombosis in trauma patients.

PMID- 7638926
TI  - [Physical prevention of thrombosis with the ankle joint with the motorized ankle
      joint movement device. Initial results of a clinical study].
AB  - Between 1993 and 1994 the value of the "Artroflow" device in deep venous
      thrombosis was tested in 95 trauma surgical high risk patients. Parallel to the
      application of Heparin and physical methods, the "Artroflow" device was employed.
      The test and compare group showed an equal amount of risk parameters and
      comparable injuries. In all patients until full mobilization a weekly clinical
      examination, a compression sonography of the deep leg veins and a venous Doppler
      examination was performed. In the test group 1 deep venous thrombosis (2.3%) and
      no clinically manifest lung embolism occurred. In the control group, the deep
      venous thrombosis rate was 21.6%. This showed a highly significant drop of the
      deep venous thrombosis rate in trauma surgical patients (p < 0.0041 Fisher test)
      and allows us to suggest the use of the "Artroflow" device in high risk patients
      parallel to heparin prophylaxis.

PMID- 7638927
TI  - [Radius fractures in typical sites in young patients--is it early osteoporosis?].
AB  - Fractures of the radius in premenopausal women caused by a slow speed trauma are
      often associated with osteoporosis. Out of 156 patients we were able to screen 26
      for osteoporosis. Bone mineral density (BMD) of the lumbar spine and the femoral
      neck was compared with the age related control group. At the lumbar spine the
      mean decrease of BMD was 13.1% (CI 95% 8.78 to 17.4%; SEM = 2.1). The patients
      showed a BMD between Z = -1 and Z = -2 and 4 patients lessen than Z = -2. At the
      femoral neck the mean decrease of BMD was 15.8% (CI 95% 11.3 to 20.3%; SEM =
      2.17). Z was between -1 and -2 in 10 patients and smaller -2 in 6 patients. There
      was no correlation between the number of risk factors and bone mineral decrease.
      All evaluated laboratory tests were within normal range. As a result of our
      investigation we suggest looking for osteoporosis in premenopausal women with
      fractures following slow speed trauma as a routine procedure to offer adequate
      therapy.

PMID- 7638928
TI  - [Hygienic requirements in parenteral administration of drugs].

PMID- 7638929
TI  - [Thoughts on the integration of the (revised) continuing education regulation and
      guidelines on the content of continuing education in the area of surgery].

PMID- 7638930
TI  - An adaptive approach to computing the spectrum and mean frequency of Doppler
      signals.
AB  - Modern ultrasound Doppler systems are facing the problem of processing
      increasingly shorter data sets. Spectral analysis of the strongly nonstationary
      Doppler signal needs to shorten the analysis window while maintaining a low
      variance and high resolution spectrum. Color flow imaging requires estimation of
      the Doppler mean frequency from even shorter Doppler data sets to obtain both a
      high frame rate and high spatial resolution. We reconsider these two estimation
      problems in light of adaptive methods. A regularized parametric method for
      spectral analysis as well as an adapted mean frequency estimator are developed.
      The choice of the adaptive criterion is then addressed and adaptive spectral and
      mean frequency estimators are developed to minimize the mean square error on
      estimation in the presence of noise. Two suboptimal spectral and mean-frequency
      estimators are then derived for real-time applications. Finally, their
      performance is compared to that of both the FFT based periodogram and the AR
      parametric spectral analysis for the spectral estimator, and, to both the
      correlation angle and the Kristoffersen's [8] estimators for the mean frequency
      estimator using Doppler data recorded in vitro.

PMID- 7638931
TI  - Simulation of two-dimensional ultrasonic imaging of biological tissues in the
      presence of phase aberrations.
AB  - A simulator of phase aberrations for mathematical modeling of two-dimensional (2
      D) ultrasonic medical imaging is developed. Principal characteristics of expected
      phase aberrations were put into the model to investigate the distorting influence
      of intervening tissues on the quality of conventional medical B-scan images.
      Information necessary for numerical simulations, including the form of the phase
      correlation function, correlation length and distortion magnitude, was obtained
      from analysis of known experimental data on abdominal and breast imaging in vivo.
      Examples of simulated acoustical images of some simple phantoms are presented.
      Improvement of image quality due to one simple phase adaptation algorithm is also
      presented.

PMID- 7638932
TI  - 20th International Symposium on Ultrasonic Imaging and Tissue Characterization.
      Arlington, Virginia, June 7-9, 1995. Abstracts.

PMID- 7638933
TI  - Prevention better than cure: problems of lameness examined.

PMID- 7638935
TI  - Prevalence of Onchocerca species and Thelazia lacrimalis in horses examined post
      mortem in Normandy.
AB  - The umbilical skin and ligamentum nuchae of 368 horses were examined post mortem
      for Onchocerca species. Only four of the horses were infected and pathological
      changes were observed on the skin of two of them. Thelazia lacrimalis was
      recovered from 38 (10.3 per cent) of the horses, and animals aged six months to
      two years were more frequently infected. No ocular lesions were observed. The
      prevalences of these two nematodes were low when compared with the infection
      rates reported in the United Kingdom and North America.

PMID- 7638934
TI  - Control of bovine tuberculosis by vaccination.
AB  - The control of bovine tuberculosis remains a significant problem in the United
      Kingdom, especially in the south west of England where the rising prevalence of
      the disease is attributed to a reservoir of Mycobacterium bovis infection in
      badgers. The possibility of controlling the disease by the vaccination of cattle
      has been unpopular with veterinarians largely because of the potential compromise
      of existing diagnostic tests. However, the vaccination of badgers to reduce the
      risk of transmission to cattle is an attractive option and has now been adopted
      as a potential control strategy. Recent research has led to important advances in
      the molecular genetics of mycobacteria and in the understanding of protective
      immune responses. These advances mean that it may be feasible to design and
      develop effective mycobacterial vaccines. This review summarises the current
      understanding of protective immunity against M bovis infection and discusses the
      possible strategies for the development of vaccines.

PMID- 7638936
TI  - Metabolic epidermal necrosis in two dogs with different underlying diseases.
AB  - Two dogs with metabolic epidermal necrosis had hyperkeratosis of the footpads
      accompanied by erythematous, erosive and crusting lesions affecting the muzzle,
      external genitalia, perineum and periocular regions. Histopathological
      examination of skin biopsies revealed a superficial hydropic dermatitis with
      marked parakeratosis. Both dogs had high plasma activities of alkaline
      phosphatase and alanine aminotransferase and high concentrations of glucose, and
      also a marked hypoaminoacidaemia. Despite these similarities, the cutaneous
      eruptions were associated with different underlying diseases. One dog had a
      pancreatic carcinoma which had metastasised widely; the primary tumour and the
      metastases showed glucagon immunoreactivity on immunocytochemical staining, and
      the dog's plasma glucagon concentration was markedly greater than that of control
      dogs. The other dog had diffuse hepatic disease; its plasma glucagon
      concentration was similar to that of control samples and cirrhosis was identified
      post mortem. Metabolic epidermal necrosis in dogs is a distinct cutaneous
      reaction pattern which may be associated with different underlying systemic
      diseases; however, the pathogenesis of the skin lesions remains unclear.

PMID- 7638937
TI  - Isolation of salmonellae from seals from UK waters.

PMID- 7638938
TI  - Completion of the veterinary written direction.

PMID- 7638939
TI  - Live animal exports.

PMID- 7638940
TI  - Tapeworm infection in donkeys.

PMID- 7638941
TI  - Lead poisoning in cattle at turnout.

PMID- 7638942
TI  - Quadriceps muscle hypoplasia causing congenital lameness in Holstein calves.

PMID- 7638943
TI  - Swan anaesthesia.

PMID- 7638944
TI  - [Vitreoretinal proliferation as a cause of tractional retinal ablation after
      severe perforating injury].
AB  - The main idea of this paper was to investigate the influence of proliferative
      reaction in vitreous body, in case of serious injuries of the eyeball on the
      development of complications. It was shown that the presence of hemophthalmia
      which intensified PVR process and anteroposterior traction influenced the
      intensity of PVR and also the development of retinal ablation. The complete
      perforation of the posterior wall of the eye ball (duplex perforation) with the
      small foreign body would produce bigger scar on the posterior wall than in case
      of singular perforations, which would usually be enough to control
      anteroposterior traction towards vitreous body and prevent retinal ablation.

PMID- 7638945
TI  - [The role and morphology of thrombocyte concentrates prepared from a buffy coat].
AB  - The results of quantification and investigation of thrombocyte morphology in 112
      concentrated thrombocyte units, prepared from buffy coat of the whole blood taken
      from the unchosen donors are shown. Immediately after the preparation of units
      the thrombocyte count was 66.99 +/- 7.04 x 10 cells (contribution of procedure
      65.05%), the number of residual leukocytes 70.2 +/- 17.91 x 10 cells and the
      value of morphological thrombocyte score was 364 +/- 32.1. During the first day
      of storage on the temperature of 20 +/- 2 degrees C, along with the constant
      shaking of units the significant decrease of number of morphological score of
      thrombocyte (p < 0.05) was stated. Beside the mentioned side effects, the units
      of concentrated thrombocytes prepared in this procedure showed to be
      therapeutically effective after the storage of 5 days. In contribution to this
      spoke electronic-microscopic investigations that showed the presence of
      degenerative changes of thrombocytes during the fourth day of storage. Further
      improvement of procedure is necessary due to the prolonged preservation of the
      concentrated thrombocyte units quality.

PMID- 7638946
TI  - [Blood autotransfusion in head and neck surgery].
AB  - Autotransfusion as a method of blood compensation after multilative surgical
      operation in cases of malignant neoplasm of the maxillofacial region, was
      introduced in our clinical practice in 1989, and up to now we have performed it
      in a group of 23 patients. It has been known that an autotransfusion depends on
      the patients' general health situation, hemoglobin level, hematocrit and iron
      concentration in serum. We exfused at least three days before operation 450 ml of
      blood from each patient. The blood was taken into plastic bags and kept in the
      refrigerator at the temperature of +4 degrees C. The decrease of serum iron
      concentration was approximately 54.26% in all tested patients that demanded the
      substitution therapy with iron together with vitamin C before and after surgery.
      There was neither prolongation of postoperative treatment nor complications
      associated with this method of post-operative blood loss compensation. Based on
      obtained results we could conclude that the best method of inter- and
      postoperative blood compensation was autotransfusion, taking care about factors
      which could limit the possibilities of its applications.

PMID- 7638947
TI  - [The effect of sodium cyanide and its antidotes on the isolated perfused rat
      heart].
AB  - The experiments were performed to investigate the effects of cyanide and several
      antidotes (sodium nitrite, DMAP, sodium thiosulfate and phentolamine) on isolated
      perfused rat heart to further elucidate the mechanism of action of cyanide and
      its antidotes. Sodium cyanide (40, 50 and 60 mg/ml) produced maximum effects on
      amplitude, heart rate and coronary flow, after 3 min, regardless of the event
      recorded. Some dose-dependence was noted, especially on the heart rate, somewhat
      less on amplitude and almost none on the coronary flow up to 15 min, but notable
      afterwards. Some spontaneous recovery occurred in each event, the most
      significant being that of the heart rate. Antidotes per se did not differ
      significantly in their action on isolated rat heart. All values, with some
      variations, were maintained within 10-20% of control. Antidotes, injected 1 min
      after sodium cyanide produced the most evident effects on amplitude and heart
      rate -- all antidotes practically and almost instantly neutralized the depressant
      effect of cyanide. Nitrite and particularly DMAP, were the most effective on
      coronary flow while other antidotes, although effective up to 3 min, did not much
      differ from cyanide alone throughout the rest of observation.

PMID- 7638948
TI  - Pulmonary pathohistological changes in mice in experimental infection with
      Pneumocystis carinii.
AB  - The infection Pneumocystis carinii was activated in mice of closely related
      BALBc/AnNCR, C57BL/6 and DBA/2 strains applying various doses of hydro-cortisone
      acetate in combination with hypoprotein or complete food. The males of all
      investigated strains showed to be more sensitive than the females and the longest
      survived mice of C57BL/6 strain. The character of pathohistological pulmonary
      changes varied depending on the duration of survival. The mature cyst forms of
      Pneumocystis carinii were confirmed in tissue applying GMS and PAP method, and
      intracystic sporozoite by GMS staining.

PMID- 7638949
TI  - [The inverse procedure in stapedioplasty].
AB  - The inverse procedure in stapedoplastic with the primary stapedectomy was done in
      55 patients with otosclerosis. The early cochleo-vestibular disorders (1.8-3.6%),
      graver sensoneural damage after 6 months (1.8%) and bone--air conduction gap were
      significantly better in relation to the patients operated in classical way. Many
      advantages of inverse procedure were analyzed in prevention of inner ear lesions
      and better functional outcome.

PMID- 7638950
TI  - [Treatment of acute migraine attacks].
AB  - Considering that migraine patients ask for the physician's help in outpatient
      clinics and hospitals due to the acute attacks dominated by headaches, the latest
      research in pathophysiology and pharmacotherapy of migraine, directed the aim of
      this research to investigate the efficiency of dihydroergotamine in the treatment
      of the acute attacks of migraine headaches and to define a treatment program of
      the acute migraine headaches for the out patient and in patient conditions. The
      investigations were performed in 34 patients of the middle age and younger, of
      both sexes, with the established clinical diagnosis of a common migraine, with no
      history of coronary disease, ischemic brain disease, kidney and hepatic
      deficiency, and who were not for different reasons, Under the prophylactic
      therapy. Patients were randomly divided into two equal groups. The first group
      was treated i.m. with dihydroergotamine (1 mg) in combination with metoclopramide
      (10 mg). In case of insufficient effect the dose was repeated after one and eight
      hours after the first dose. The second group was treated with diclofenac (75 mg)
      and metoclopramide (10 mg), using the same pattern. The results investigation
      showed the significantly better effect of dihydroergotamine regarding the onset
      and the intensity of the positive effect. It was concluded that in case of acute
      attacks of migraine headaches in younger patients with no history of coronary
      disease, ischemic brain disease, kidney and hepatic deficiency, dihydroergotamine
      with metoclopramide administered i.m. could be used as a therapy of choice in all
      treatment conditions.

PMID- 7638951
TI  - [Contribution of fiber optic bronchoscopy to the etiologic diagnosis of bacterial
      pneumonia].
AB  - In 24 patients with bacterial pneumonia, reliability of the samples routinely
      taken for etiologic diagnosis (sputum, throat swab, bronchial brushing,
      bronchoalveolar lavage fluid--BALF, blood, pleural fluid) was determined.
      Organisms detected in blood, pleural fluid, transbronchial biopsy (TBB) or
      percutaneous transthoracic needle aspiration biopsy (PTNAB) samples were
      considered as truly causative, whereas those isolated in at least two various
      samples from a single patient were considered as presumably causative. Most
      sensitive diagnostic samples were BALF, TBB and PTNAB (100% each). However, the
      specificity of BALF was very low (17%). Bronchial aspirate was highly sensitive
      (95%) but not specific (14%). Bronchial brushing was sensitive (86%) but its
      specificity low (14%). Sputum was hardly sensitive (40%) and had no specificity.
      Throat swab had virtually no diagnostic value because of its low sensitivity
      (10.5%) and specificity (50%).

PMID- 7638952
TI  - [Is it possible that hepatitis virus A can cause autoimmune liver disease?].

PMID- 7638953
TI  - [Stiff-man syndrome].

PMID- 7638954
TI  - [Moyamoya associated with cerebral arteriovenous malformations--case report].

PMID- 7638955
TI  - [An example of double glomerulonephritis with nephrotic syndrome].

PMID- 7638956
TI  - [The health culture and beginnings of organized health care in Montenegro].

PMID- 7638957
TI  - [Personal experience in the care of thoracic war injuries 1992-1993].
AB  - The aim of this paper was to clear some dilemmas about the surgical treatment of
      chest injuries. In the period April 1992-December 1993 in the General Hospital of
      Foca 160 chest injuries were treated (71 penetrating and 89 unpenetrating
      injuries) that was 10.2% of the total number of injuries. The explosive injuries
      were 53.8% of cases and 46.2% sclopetary injuries. Those injuries dominated in 93
      wounded and in 57 cases the injuries were associated. The isolated injuries were
      in 40% and combined ones in 60% of cases. Thirty five thoracotomies and 40 thorax
      drainages were done while on the rest of the wounded only surgical wound
      treatment was performed. The active immunization and antibiotic prophylaxis were
      performed on the wounded. The infection problem was present in one operated
      person and lethality rate was 4.4%. The treatment results were good due to the
      appropriate organization of the surgical service and timely primary specialist
      aid as well as sufficient quantity of blood and timely and adequate surgical
      procedure.

PMID- 7638958
TI  - [Detection of Toxoplasma gondii DNA in body fluids by polymerase chain reaction].
AB  - The polymerase chain reaction (PCR) is used for in vitro amplification of
      specific DNA fragments. The PCR technique is based on the reiteration of a three
      step process: denaturation DNA into single strands, annealing primers (specific
      synthetic oligonucleotides) to the DNA template and enzymatic extension from the
      primers along the templates. The usefulness of this new technique to the
      detection of Toxoplasma gondii DNA has been described.

PMID- 7638959
TI  - [Detection of coproantigens in parasitic diseases].
AB  - The author presented general issues in detecting of parasite's coproantigens and
      carried out a critical review of abstracts submitted to the scientific session
      (17th Congress of the Polish Parasitological Society, September 1994, Gdynia,
      Poland). The abstracts are being published in a special edition of the
      "Methodical and Organisational Bulletin" (Institute of Marine and Tropical
      Medicine, Gdynia, Poland).

PMID- 7638960
TI  - [Waterborne outbreaks of Giardia].
AB  - The authors present the actual informations on waterborne outbreaks of giardiasis
      as well as the evidences of Giardia cyst transmission by municipal water supply.
      In the article a recommendations is given to molecular biology techniques which
      contributed to the armentarium applied in the modern diagnostics of giardiasis.

PMID- 7638961
TI  - [Usefulness of genome analysis methods for diagnosis of giardiasis and
      cryptosporidiosis].
AB  - The article comprises a critical review on practical applications of molecular
      technology in parasitological diagnostics in a broad sense, also as a diagnosis
      of species and a method of epidemiological analysis. Techniques of genome
      analysis at different levels, as specific nucleic acid probes, DNA restriction
      profiles (RFLP), hybridization techniques, pulse-field gel electrophoresis, in
      vitro nucleic acid amplification, and DNA fingerprint technique used in studies
      on Giardia and Cryptosporidium were discussed. The essential reservation as far
      as this technology is concerned refers to its usefulness in parasitological
      diagnostics; there is no sense in working out methods for recognizing parasites
      which could otherwise be identified by well trained parasitologists and simple
      microscopic methods. The improved diagnosis of parasites resulting from the
      application of molecular technology significantly contributed to the armarium of
      parasitologists. Application of recent molecular technology in diagnosis of
      giardiasis and cryptosporidiosis may basically support clinical diagnosis which
      provides possibilities of early and selective treatment and makes possible
      epidemiological studies. These assays will permit not only a rapid diagnosis and
      exact differentiation but will also enable a better recognition of Giardia and
      Cryptosporidium genome organization. However, in spite of the wide availability
      of this new techniques they have not been fully applied--as yet--in diagnosis and
      in epidemiological studies on these parasites. The authors share the opinion of
      Busch (1991) on the need of proper recognition of high-quality and rigorous work
      in employing new molecular assays, because their wide availability and high
      sensitivity could cause "false-positive" results by contamination with amplified
      DNA sequences.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7638962
TI  - Intensified morphological variability during patency in Hymenolepis diminuta
      originating from inbred tapeworm--WMS IL1.
AB  - Variable position of genital ducts and pores (PGP) was found in 23.3% of five
      months old tapeworms obtained as a result of administering to rats a dose of 6
      cysticercoids proceeding from the third generation of inbred Hymenolepis diminuta
      -WMS il1. In tapeworms coming from generations no 18 and 32 PGP changes were
      reported only in 7.5 month, with only 5.9% of strobilas in the 32 generation
      group being characterized by this feature. These results indicate a time shift
      with respect to the appearance of PGP changes in tapeworms proceeding from latter
      inbred generations to a further period of tapeworm invasion in rats. The number
      of PGP changes is positively correlated with the number of type 2p1a proglottids
      (two testes on the poral and one on the aporal side). The average number of type
      Op3a proglottids increases with the number of generations. In 5-month old
      tapeworms of unilateral PGP coming from generation no 3, 18 and 32 it amounts to
      5.9%, 6.6% and 8.1%, respectively.

PMID- 7638963
TI  - [Contemporary strategies and methods of modeling antiparasitic drugs].
AB  - Contemporary methods of directed chemotherapy are based on multi-step procedures,
      which require co-ordinated activities of interdisciplinary teams of biochemists,
      pharmacologists, geneticists, crystallographers as well as computer scientists.
      Biochemists select the proper target, such as an enzyme, throughout screening of
      the biochemical influence of compounds-potential drugs on this target. For
      further research they use targets with very low inhibition constants (> 10(-6)
      M). Determination of the relation between therapeutic activity of the compound
      and modelling of its chemical structure constitutes an important part of the
      procedure. The most important part of the procedure is the recognition of the
      primary structure of the target. The two following pathways allow to do that: 1.
      isolation of DNA and gDNA or cDNA-started cloning of a gene responsible for
      production of the target protein and then its sequencing. 2. purification and
      crystallization of the target protein and further computer-aided processing of
      crystallographic data in order to determine the primary structure. Computational
      chemistry (C/C) methods are the basic part of the procedure of molecular
      modelling (M/M) of a target molecule and its interactions with a molecule of the
      future drug. Data obtained using a technology which engages the C/C and M/M
      methods not only allow to determine the aminoacid sequence of the target protein
      in question (e.g. a unique parasite enzyme); they also enable to further
      speculate on its secondary and tertiary structures. Such structure includes
      specified number of repeated motifs of alpha-helixes, beta-sheets and loops or
      turns. Particularly, the "barrel" structure is very common in numerous enzymes.
      Two following examples of research on target-antiparasitic drug interactions is
      presented. They are the interaction between phosphoglicerate kinase in Leishmania
      and drug suramin and malic enzyme of Trichinella and drug closantel. New
      promising targets for new anti-protozoan drugs (protozoa of Trypanosoma species)
      include e.g. microbody translocation signal in kinetosom proteins (SKL) or
      protein blocking the transport of proteins to glycosomes-metabolic centres in
      Trypanosoma (repetitive groups of QRLQ). Recently, scientists from Arris
      Pharmaceutical (San Francisco) have considered, employing new data, up to 100 to
      fully characterize the surface structure of a molecule, using the systems of
      artificial intelligence.

PMID- 7638964
TI  - [Karyometric analysis of selected neurohormonal cells of the snail Lymnaea
      stagnalis (L.) under conditions of natural infection with digenetic trematode
      parthenites].
AB  - To supply more documentary evidence for the effect of parasitic infection on
      activity of neurosecretory centres in the cerebral ganglia of the snail host,
      caudo-dorsal and light green cells of adult individuals of Lymnaea stagnalis
      naturally infected with digenean parthenites were subjected to karyometric
      analysis. In infected animals significant enlargement of nuclear volumes of both
      examined types of neurosecretory cells was ascertained. Mean nuclear volume of
      the light green cells in snails infected with Furocercariae was significantly
      lower in comparison with the individuals infected with parthenites from groups
      Echinostomata and Xiphidiocercariae. In remaining cases differences in nuclear
      volumes among subpopulations distinguished on the ground of an infection factor
      were not statistically significant.

PMID- 7638965
TI  - [Immunity against tick-borne encephalitis in healthy residents of endemic areas].
AB  - Specific IgG antibodies against Tick-Borne Encephalitis Virus (anti-TBEV) at
      levels exceeding 60 VIEU/ml were detected in almost 14% of forestry workers and
      in 1.5% of other healthy persons, residents of the endemic area. Mean levels of
      anti-TBEV were similar in comparable subgroups of men and women, or subgroups of
      urban and rural residents, however, increased levels of these antibodies were
      found in elderly persons.

PMID- 7638966
TI  - [Evaluation of soil sanitation on Poznan beaches based on helminth examination].
AB  - It was proved that the soil of recreational areas can be potential source of
      human geohelminthiosis. The eggs of Ascaris lumbricoides and Trichocephalus
      trichiurus as well as of Toxocara canis were found on the beaches of Poznan
      lakes.

PMID- 7638967
TI  - New species of mites collected on Tenebrionidae, Scarabaeidae, Cerambycidae and
      Lucanidae with the description of new subfamily Vereoxiinae (Acari, Astigmata,
      Canestriniidae).
AB  - A new subfamily Vereoxiinae among Canestriniidae is created for the new genus
      Vereoxia with one species V. bogeri n. sp. Four new canestriniid species are
      described: Gasuthiana melillae n. sp. from undetermined Tenebrionidae, Brazil,
      Afrocanestrinia rufinae n. sp. from Smaragdesthes oertzeni, Tanzania, A. samsoni
      n. sp. fromS. africana, Senegal, Canestriniella phoebinae n. sp. from Batocera
      albofasciata octomaculata, Java. New diagnosis of the genera Gasuthiana,
      Afrocanestrinia and Canestriniella are given.

PMID- 7638968
TI  - Regulation of smooth muscle cell proliferation and its possible role in
      preventing restenosis post-angioplasty.
AB  - The introduction of balloon angioplasty in 1978 as an alternative treatment for
      vascular stenosis has created a new clinical problem: restenosis, the renarrowing
      that occurs after the procedure in certain patients. Restenosis is an important
      long-term complication, with an incidence of 30-50% within 6 months post
      angioplasty. Three mechanisms contribute to vascular restenosis: recoil, thrombus
      formation and direct trauma. Growth factors which enhance the expression of other
      growth-regulating proteins, in particular "second messengers", proto-oncogenes
      and other cell cycle controlling proteins, are released by local thrombi and the
      injured arterial segment itself, resulting in an excessive inflammatory and
      myofibroproliferative response which culminates in restenosis. From
      investigations in animal models it is known that restenosis takes place in
      several phases: thrombosis, inflammation, cell proliferation and matrix
      formation. Various factors seem to interact in each particular phase, either as
      agonists or antagonists; hence the pathway that results in restenosis is complex.
      The introduction of directional percutaneous atherectomy has made it possible to
      examine human arterial tissue obtained in vivo, including restenosis material,
      from a sufficient number of patients in order to complement animal experiments.
      Not all of the mechanisms which lead to restenosis are known; nevertheless, after
      more than 15 years' experience of balloon angioplasty, there is an urgent need to
      develop therapeutic strategies based on currently available information.
      Selective elimination or alteration of proliferating cells, enhancement of
      natural growth inhibitors, blocking of signal transduction or inhibition of the
      gene expression for distinct growth-stimulating proteins all appear to be
      potentially promising.

PMID- 7638969
TI  - [Isosorbide-5-mononitrate in silent ischemia].
AB  - Thirty six patients with documented coronary artery disease and exercise-induced
      silent ischemia were evaluated in a double-blind randomised placebo-controlled
      crossover study. The effect of once daily 60 mg sustained-release isosorbide-5
      mononitrate (IS-5-MN) was tested on exercise-induced and ambulatory silent
      ischemia. After a wash-out period in which no cardioactive drugs were
      administered, each patient received IS-5-MN for the first week, followed by
      placebo for the second week, or vice versa. A symptom-limited bicycle exercise
      test and Holter monitoring over a 24-hour period were performed after wash-out
      and at the end of each one-week treatment period. In comparison with wash-out IS
      5-MN significantly (p < 0.05) prolonged time on onset of 1 mm ST-segment
      depression during exercise testing. On the other hand, the number and circadian
      variation of ischemic episodes during Holter monitoring were not influenced by IS
      5-MN. Thus, 60 mg IS-5-MN once daily significantly improved silent ischemia
      during exercise testing but not during Holter monitoring. This discrepancy may be
      due to different pathogenetic mechanisms of ischemia during ergometry as opposed
      to the everyday situation; nitrates may also provoke silent ischemia by
      increasing the heart rate. Furthermore, the choice of only one antiischemic drug
      at a fixed dosage may not be aggressive enough in suppressing ischemia
      completely.

PMID- 7638970
TI  - [Chronic thromboembolic pulmonary hypertension and its treatment with pulmonary
      thrombendarterectomy].
AB  - Chronic recurrent pulmonary embolism can lead to extensive pulmonary hypertension
      by obstruction of the pulmonary vessels. Pulmonary thrombendarteriectomy is a new
      approach to normalizing the elevated pulmonary vascular resistance by removal of
      the adsorbed thrombi. Between 1992 and 1994 we have operated on 8 patients aged
      between 34 and 62 years. The first patient died due to extensive reperfusion
      edema, all others showed significant improvement in hemodynamic parameters (mean
      pulmonary artery pressure preop. 63 +/- 5 mmHg; postop. 30 +/- 9 mmHg; Cardiac
      Index preop. 2.0 +/- 0.2 l/min; postop. 3.5 +/- 0.5 l/min; pulmonary vascular
      resistance preop. 1169 +/- 75 dyn; postop. 228 +/- 55 dyn) and exercise
      performance (NYHA classification preop. III-IV, postop. I-II). Pulmonary
      thrombendarteriectomy represents an efficient method to normalize elevated
      pulmonary pressure and exercise performance of patients with far-advanced chronic
      thromboembolic pulmonary hypertension.

PMID- 7638971
TI  - [Emergency house calls in a Vienna medical practice].
AB  - Daytime emergency visits (7 a.m.-8 p.m.) requested in a general practice on the
      outskirts of Vienna were investigated between 1985 and 1992. Altogether 56 such
      calls were registered, on average 7.1 per year, with a decreasing tendency over
      the investigated period. The average visit started 9 minutes after demand and
      lasted for 17 minutes. An objective assessment after the visits revealed 35.7%
      life-threatening indications, 57.1% absolute, 3.6% relative and 3.6% trivial
      indications. Only 34% of all patients were referred to hospital for inpatient
      treatment. This form of general practitioner home visiting based on telephone
      assessment of urgency by the doctor personally keeps calls to a minimum, saves
      money and is efficient.

PMID- 7638972
TI  - [Voice--mood: psycholinguistic therapy with psychiatric patients].
AB  - The voice is the result of a complex network between mental condition, mood and
      cognition of a person. The voice not only serves as a means of communication, it
      has also an effect on the person who is uttering the sounds. Language development
      phases and the emotional development phases form the theoretical base for
      therapeutic interventions. The way the therapist proceeds depends on the
      momentary mental state the patient is in. The structuring of the intervention
      levels depends on the degree of the disorder. In patients with pronounced
      inhibitions the therapist tries to activate the patient's feelings by means of
      passive breathing exercises and kinaesthetic awareness exercises which are
      accompanied by low music (awareness phase). Once a patient is successfully
      activated, she/he is asked to actively breathe and use her/his voice for reading
      and reciting purposes. The texts are accompanied by appropriate music
      (instrumental phase). This intervention is meant to lead the patient away from
      his/her egocentric state towards social interaction. After an amelioration and/or
      stabilisation of the psycho-pathological state, therapeutic activities are
      continued in the setting of group work. Patients with disorders primarily in the
      social area take part in this group work right from the start of therapy. The
      patients learn social strategies in that they get practice in creatively working
      with texts in the form of readings and theatre performances. They also learn how
      to throw a party together. In this phase they realise their abilities but also
      their limits (communicational phase). Due to the playful character of the work in
      the group the patients experience themselves independently; they leave the
      passive role of the patient and become active human beings. That way this form of
      therapy provides a bridge between the "biotope" of the stationary area and
      everyday life.

PMID- 7638973
TI  - [Diagnostic imaging in follow-up of surgically treated stenosis of the aortic
      isthmus in adolescents and adults].
AB  - Local abnormalities of the ascending aorta, especially at the site of correction
      are well known complications after surgical correction of aortic coarctation.
      Regular follow-up is therefore necessary. Besides chest X-ray, transesophageal
      echocardiography and substraction angiography, magnetic resonance imaging (MRI)
      and computertomography (CT) provide a complete and noninvasive examination of the
      great vessels. MRI and CT are ideally suited for this purpose.

PMID- 7638974
TI  - [Patient education in multiple sclerosis: experiences and wishes of affected
      patients].
AB  - 110 patients suffering from multiple sclerosis (MS) were asked about their
      experiences and their preferences concerning patient information. 85% were
      informed about diagnosis by physicians. The time from the occurrence of first
      symptoms until information about the diagnosis was 5.6 years on average. Most of
      our patients require frankness, but 29% would prefer to be informed only after
      disabilities have occurred. Contradictory statements of some patients seem to
      express their ambivalent feelings. It is difficult and needs a lot of sensitivity
      to find the best moment and the right quantity of information a patient is able
      to accept.

PMID- 7638975
TI  - Views of women in Yoruba culture and their impact on the abortion decision.

PMID- 7638976
TI  - Family work demands, employment demands and depressive symptoms in women with
      rheumatoid arthritis.
AB  - The effects of psychological demands, work autonomy and social support on
      psychological well-being are evaluated in a sample of employed women with
      rheumatoid arthritis (RA). Two hundred sixty-seven employed women with a
      diagnosis of RA were recruited from a national random sample of private
      rheumatology practices. Women were interviewed by telephone and data were
      obtained on demographic variables, health status, demands in paid and family
      work, autonomy in paid and family work, social support and depressive symptoms.
      Women reported relatively high levels of psychological demands in both paid and
      family work, with time constraints being the most frequent problem. Women also
      had relatively high levels of autonomy in family work. Hierarchical regression
      analysis showed that family demands appeared to be more important than paid work
      demands in psychological well-being. High autonomy in family work seemed to
      mediate the effects of family demands. Having higher social support reduced the
      effects of work demands on depressive symptoms in employed women with RA.

PMID- 7638977
TI  - Missouri's parental consent law and teen pregnancy outcomes.
AB  - The Supreme Court decision of July 1989 upholding state regulation of abortion
      has led to numerous attempts to impose parental consent and/or parental
      notification legislation for females under the age of 18 seeking abortions. The
      effect of such legislation on teen pregnancy outcomes is hotly debated. Missouri
      vital statistics data from 1980 through 1992 are examined for the effect of such
      a law on pregnancy resolution choices among teens. The Missouri data suggest that
      since the enforcement of the parental consent statute in 1985 there has been a
      decrease in the selection of abortion as a pregnancy outcome, particularly among
      white teens. In addition there has been an increase in the percent of abortions
      among teens taking place in other states and an irregular but steady trend toward
      later abortions. The increasing number of births to unmarried mothers under the
      age of 18 suggest the need for specific services to help these young mothers
      cope.

PMID- 7638978
TI  - The time of first holding of the infant and maternal self-esteem related to
      feelings of maternal attachment.
AB  - This study tested the hypotheses that the earlier the mother holds her infant
      after delivery the sooner she will develop feelings of maternal attachment, and
      the more positive her self-esteem the sooner she will develop feelings of
      maternal attachment. A voluntary sample of 67 mothers completed self-administered
      questionnaires including the Rosenberg Self-Esteem Scale and three tools designed
      for use in this study. Findings from Pearson product-moment correlations
      supported the first hypothesis but not the second. Implications for health care
      practice and research are discussed.

PMID- 7638979
TI  - Older women and health services: moving from ageism toward empowerment.
AB  - Ageism and sexism in health services and research affect the quality of care,
      patient-provider interaction, patient self-perceptions, and the planning of
      health education programs for older women. Stereotyping of older women in the
      health care encounter, although often subtle, can have far-reaching effects on
      the health status of older women. Prevailing research methodologies are focused
      on disease processes and neglect older women's subjective experience of illness.
      Changes at the organizational, community, and individual levels that promote the
      autonomy and empowerment of older women are discussed.

PMID- 7638980
TI  - Papers from a meeting on malignant melanoma. Brisbane, April 1994.

PMID- 7638981
TI  - Current melanoma epidemic: a nonmetastasizing form of melanoma?
AB  - During the mid to late 1980s in white populations in Australia, New Zealand, and
      Scotland, melanoma incidence increased sharply above preceding long-term trends.
      Most of this increase was in thin melanomas (< 1.50 mm thick), and men were more
      affected than women. Thick melanomas also generally increased in incidence,
      particularly in men 65 years or older. Although advancement of the time of
      diagnosis was a likely factor in the increase in melanoma incidence, the
      maintenance of new higher incidence levels and the increase in the incidence of
      thick lesions indicated that earlier diagnosis did not explain most of the
      increase. Real increases in incidence due to continuation of long-term trends and
      the increasing diagnosis of a preexisting, nonmetastasizing form of thin melanoma
      probably explain most of the recent increases in melanoma incidence.

PMID- 7638982
TI  - Childhood melanoma in Australia.
AB  - Data from a population-based registry, the Australian Paediatric Cancer Registry,
      were used to determine the incidence of malignant melanoma in children under 15
      years of age in Australia. Over a 17-year period, 217 cases were identified. For
      the period 1977-89 inclusive, the annual age incidence was 0.34 per 100,000.
      There was some variation in incidence between the different states with
      Queensland recording the highest incidence at 0.97 per 100,000, the highest
      reported incidence in the world for childhood melanoma. Most of the cases
      occurred in children aged 13 or 14 years old with girls affected slightly more
      often, the sex ratio being 0.92. There was a statistically significant seasonal
      variation with fewer cases being diagnosed during the winter months. The
      commonest site was the trunk. Two of the cases were second neoplasms. This series
      demonstrates the need for increased education of children living in tropical and
      subtropical regions about the dangers of sun exposure and of methods of reducing
      exposure. Children who have undergone chemotherapy appear to be at particular
      risk.

PMID- 7638983
TI  - Megestrol melanoma study.
AB  - The progestogen megestrol acetate (160 mg/day PO continuously starting 2 days
      before chemotherapy) plus chemotherapy with dacarbazine (220 mg/m2/day IV for 3
      days), cisplatin (25-30 mg/m2/day IV for 3 days) every 3 weeks, and carmustine
      (150 mg/m2 IV single dose every 6 weeks) were administered to 22 patients, 18 of
      whom were evaluable. Toxicity was tolerable, and more than 80% of ideal dosing
      was achieved during the first two cycles of treatment. A net weight gain of 0.95
      kg was observed during this program of treatment. A 56% objective response rate,
      including visceral responding sites, with a median duration of response of 37.5+
      weeks was achieved. A median survival of 15 months for all evaluable study
      patients was seen, which is somewhat longer than that achieved by most prior
      studies, including those employing the same chemotherapy regimen plus tamoxifen.
      Megestrol acetate may contribute to a high objective response rate and prolonged
      median survival in viscerally dominant metastatic melanoma when used with a
      chemotherapy regimen of dacarbazine, carmustine, and cisplatin.

PMID- 7638984
TI  - Recommended width of excision for primary malignant melanoma.
AB  - Wide local excision for melanoma with margins of 3 to 5 cm have been advocated in
      the literature for nearly 140 years. These reports have grouped all stages of
      melanoma rather than addressing primary early stage disease. Breslow first
      advocated limited excision margins for these tumors. We have been excising all
      thicknesses of melanoma with a limited margin (1.00-1.50 cm, mostly 1.00 cm)
      since 1975. We advocate a 1 cm excision margin irrespective of tumor thickness.
      Clark has shown that melanoma invades in a vertical fashion, and thus one would
      expect to be more generous in depth than in width on a pathologic basis. Two
      studies have shown that there is no difference in the increase in locoregional
      recurrence and no change in death rate from the disease with more conservative
      treatment margins. Excision of this lesion is not an office procedure. It should
      be performed meticulously in an operating room, preferably under light general
      anesthesia.

PMID- 7638985
TI  - Local melanoma recurrences in the scar after limited surgery for primary tumor.
AB  - The clinical and histologic records of 46 consecutive patients were reviewed who
      during the period 1980-1993 had recurrence from melanoma in the scar after
      limited surgery for a skin tumor. They constituted about 50% of all patients
      admitted with local recurrence from melanoma during this period. At reexamination
      of the primary tumors, 16 were found to be malignant melanomas and 9 were nevi
      (four atypical and five benign). Twenty-one were missing, 11 of which had never
      been set for histologic examination. The median thickness of nine measurable
      melanomas was 0.66 mm. The recurrences in scar consisted of 34 primary melanomas:
      18 superficial spreading, 4 nodular, 3 lentigo malignant, and 9 unclassified.
      Twelve tumors were dermal melanoma metastases. The median thickness of the 25
      measurable melanomas was 0.78 mm. The 5-year overall survival was 69%. At the
      closing date of the study 15 patients had died, 13 of them because of
      disseminated melanoma. A comparison of the survival curves from this study with
      those from other series of melanomas with comparable tumor thickness indicates a
      considerably worse prognosis than is expected with such thin tumors. We believe
      that the considerable number of local recurrences in the form of a new primary in
      a scar following limited surgery supports the theory of limited field change
      around a primary melanoma. Furthermore, limited procedures for primary melanoma,
      if followed by a recurrence in the scar, worsen the prognosis.

PMID- 7638986
TI  - Involvement of the 4q21 region in human malignant melanomas: cytogenetic and
      immunocytochemical characterization of three primary cell cultures.
AB  - The GRO1 oncogene (melanoma growth-stimulating activity alpha) has been localized
      in region 4q21. The involvement of this chromosomal region in clonal aberrations
      found in primary melanoma cell cultures could have an important role in the
      etiology and pathogenesis of this tumor. We characterized three primary cell
      cultures obtained from different patients, each of which showed clonal
      chromosomal aberrations involving the 4q21 region.

PMID- 7638987
TI  - Spontaneous regression of human melanoma/nonmelanoma skin cancer: association
      with infiltrating CD4+ T cells.
AB  - Spontaneous regression occurs in some human malignant melanomas and basal cell
      carcinomas (BCCs). We have compared the cellular infiltrate in regressing and
      nonregressing tumors in order to analyze the mechanism by which regression
      occurs. Regressing primary melanomas and BCCs were infiltrated with a larger
      number of CD4+, but not CD8+, T lymphocytes than were seen in nonregressing
      tumors. The number of interleukin 2 receptor-positive (early activation marker)
      but not transferrin receptor-positive (intermediate activation marker) T cells
      was increased, indicating that the infiltrating T cells were activated. Large
      numbers of Langerhans cells, macrophages, and other class II major
      histocompatibility complex (MHC)-expressing cells were present but were not
      increased in the regressing tumors. There were no detectable B lymphocytes, and
      the regressing tumor cells displayed levels of HLA-DR expression similar to those
      of the nonregressing tumors. Comparison of squamous cell carcinoma (SCCs) with
      keratoacanthomas (KAs), which are likely to be a spontaneously regressing form of
      SCC, also showed increased infiltration of activated CD4+, but not CD8+, T cells
      within the KA. A murine ultraviolet (UV)-induced squamous tumor that
      spontaneously regresses when transplanted into immunocompetent syngeneic mice was
      also infiltrated with increased numbers of activated CD4+, but not CD8+, T cells
      prior to and during rejection. These results indicate that spontaneous regression
      of human skin tumors is likely to be immunologically mediated, and that CD4+ T
      lymphocytes seem to mediate this regression.

PMID- 7638988
TI  - Local hyperthermia and systemic chemotherapy for treatment of recurrent melanoma.
AB  - Thirty-two patients with recurrent (skin) or metastatic (skin, node, or both)
      melanoma have been treated with a hyperthermia-cisplatin regimen. The
      hyperthermic treatment was carried out for 60 minutes at 43 degrees C with the
      MHS-SMA and the Sapic SVO3 ALENIA devices once a week. When the tumor temperature
      reached 42 degrees C, cisplatin was administered at a dosage of 50 mg/m2 given by
      intravenous bolus infusion. The treatment was repeated four times and the tumor
      response evaluated 4 weeks after the last treatment. Significant systemic or
      local toxicity was not seen. In terms of results, there were 9 patients with
      complete responses (28.1%), 13 with partial responses (40.6%), 8 with no change
      (25.0%), and two with disease progression (6.3%). The objective response rate was
      68.7%. The response duration for those with complete responses ranged from 4 to
      49 months (median 20 months). The median time to progression for patients with
      partial responses and those with no change was 6 and 5 months, respectively, with
      ranges of 1-7 and 1-10 months, respectively. The 4-year actuarial survival rates
      were 47.6% and 20.3% for the complete and incomplete responders, respectively.
      These results can be considered satisfactory, taking into account that most
      patients were pretreated with radiotherapy, chemotherapy or both, confirming the
      therapeutic potential of the hyperthermia and cisplatin regimen.

PMID- 7638989
TI  - Hyperthermic isolated limb perfusion for malignant melanoma: response and
      survival.
AB  - Response to and survival after hyperthermic isolated limb perfusion (HILP) with
      melphalan in patients with malignant melanoma at the Royal Brisbane Hospital were
      reviewed in order to assess the major determinants of response to treatment. Data
      were collected by clinical chart review and direct patient contact. Response was
      assessed by clinical observation and measurement of nodules. Survival was
      calculated from the date of perfusion to the date of patient death. Since 1965
      there have been 85 patients (38 men, 47 women) who have undergone 109 limb (102
      leg, 7 arm) perfusions. The mean age was 58 years (range 32-82 years). The number
      of patients per disease stage (M.D. Anderson classification) was as follows:
      stage I, 5 patients; stage II, 8 patients; stage IIIa, 41 patients; stage IIIab,
      25 patients; and stage IIIb, 8 patients. The mean duration of perfusion was 81
      minutes. Melphalan was given in divided doses, with a mean total dose 1.39 mg/kg.
      The mean maximal limb temperature was 41.5 degrees C. Major complications
      occurred during 20 perfusions (18%). There was one postoperative death from
      myocardial infarction, and one patient required amputation. Median patient follow
      up was 2.65 years (range 1-27 years). A complete response was noted in 34
      patients (40%), a partial response in 36 patients (42%), and no response in 11
      patients (13%). Response could not be assessed in four patients. The actuarial 5
      year survival for the whole group was 45%: stage I, 80%; stage II, 75%; stage
      IIIa, 44%; stage IIIab, 23%; stage IIIb, 56%. The two significant determinants of
      response to perfusion were disease stage (p = 0.00005) and nodal status (p =
      0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7638990
TI  - Radiation therapy for nodal disease in malignant melanoma.
AB  - Radiation therapy has been widely used for palliative management of inoperable
      metastatic malignant melanoma. For patients with nodal disease, response rates of
      approximately 70% have been reported. There are limited data concerning the role
      of adjuvant irradiation following therapeutic lymph node dissection. In this
      review, 57 patients with isolated resectable and nonresectable nodal disease have
      been treated with radiation. The overall response rate is 84% for bulky disease.
      Large fractions are beneficial. The median disease-free survivals were 11 months
      after adjuvant treatment and 7 months for those with inoperable disease. The
      median overall survivals were 20 months and 18 months, respectively. Local
      control in long-term survivors was excellent. Sixty-five percent of patients
      developed distant metastases. There is a need for additional studies with the use
      of adjuvant radiation therapy following lymph node dissection.

PMID- 7638991
TI  - Diagnostic outcome of repeated mammography screening.
AB  - Mammographic screening for breast cancer within health service routines was
      evaluated for the years 1987-1992, with special focus on repeated screening
      during 1989-1992. The overall attendance rate by women aged 40 to 74 years was
      82.8%. During 1989-1992 malignancy was found in 2.6/1000 screened women, giving a
      87.4% positive predictive rate at surgery and 95.9% efficiency. Among women aged
      > or = 45 years, the positive predictive rate was > 94%. Fine-needle aspiration
      (FNA) biopsy showed invasive cancers in 84% and highly suspected cancer in
      another 15%; 60% of the lesions were nonpalpable. For first-time (prevalence)
      screening (1987-1988) the positive predictive rate was 86% and the malignancy
      yield 6.4/1000. In women aged 40-44 years there were few surgical referrals
      (1.6%), but the positive predictive rate at surgery was only 48.3%, indicating
      diagnostic difficulties in young women. The median size of all invasive cancers
      was 12 mm: 84% were classified as pT1, and 23% had lymph node involvement. Stage
      II disease was found in 27% of all malignancies. The use of FNA in the diagnostic
      workup for breast cancer screening is of crucial importance to the maintenance of
      high positive predictive rates at surgery. Moreover, regular analysis is
      important even when mammographic screening is incorporated into the routine work
      of health services.

PMID- 7638992
TI  - Tuberculosis of the breast masquerading as carcinoma: a study of 100 patients.
AB  - One hundred patients with tuberculous mastitis were referred to the Tata Memorial
      Hospital, a cancer center, with a clinical diagnosis of malignancy. This study
      identifies the possible causes of misdiagnosis and reviews the management of
      these patients. A lump in the breast with or without ulceration was the commonest
      presentation, the others being diffuse nodularity and multiple sinuses.
      Concomitant axillary lymph nodes were found in one-third of the patients.
      Tuberculosis lesions such as nodular mastitis, disseminated mastitis, and
      sclerosing lesions clinically mimicked a fibroadenoma, carcinoma, and fibrocystic
      mastitis depending on the mode of presentation. A young, multiparous, lactating
      woman with a lesion should arouse the suspicion of tuberculous mastitis, although
      pretherapeutic pathologic confirmation of a benign disease is mandatory.
      Mammography, fine-needle aspiration cytology, and excision biopsy for this
      purpose are successful in 14%, 12%, and 60% of cases, respectively. Acid-fast
      bacilli were identified in 12% patients. All patients received antituberculous
      chemotherapy, and 14% patients required simple mastectomy, due to either lack of
      response to chemotherapy (10%) or large painful, ulcerative lesions involving the
      entire breast (4%). Axillary dissection was performed in only 8% patients with
      large ulcerated axillary nodes. All patients, followed for a minimum of 2 years,
      were free of disease after therapy.

PMID- 7638993
TI  - Laparoscopy for management of nontraumatic acute abdomen.
AB  - The diagnostic and therapeutic influence of laparoscopy has been studied in 255
      patients presenting with nontraumatic acute abdominal pain. Laparoscopy provided
      a correct diagnosis in 93% (236 of 255) of the cases, the others requiring a
      laparotomy. An erroneous preoperative diagnosis was corrected by laparoscopy in
      50 patients (20%), which called for a change of treatment in 25 patients (10%).
      Seventy-three percent (186 of 255) of acute abdominal conditions were treated
      exclusively by laparoscopy, 23% (58 of 255) by conventional surgery, and 4% (11
      of 255) by laparoscopically assisted surgery. Mortality was 2% (5 of 247) and
      morbidity 11% (28 of 247). We conclude that laparoscopy is a valuable tool for
      the general surgeon facing a patient with an acute abdomen.

PMID- 7638994
TI  - Clinical management of blunt trauma patients with unilateral rib fractures: a
      randomized trial.
AB  - Optimal pain management is essential in blunt trauma patients sustaining
      significant chest trauma. The purpose of this randomized prospective trial was to
      measure the difference in pulmonary function in nonintubated patients with
      unilateral multiple rib fractures receiving two modalities of pain relief:
      systemic narcotic medications alone or local anesthetics given by intrapleural
      catheter (IPCs). Forty-two patients were randomized to receive systemic narcotic
      medications or IPCs for pain control. The patients with IPCs statistically had
      more compromised pulmonary function as measured by forced vital capacity (FVC) on
      admission; however, they tended toward a greater objective improvement of FVC on
      discharge. When analyzing a cohort of severely impaired patients (initial FVC <
      20%), half of the systemic medication patients compared to only 10% of the IPC
      group failed and required another mode of therapy. Catheter complications were
      minor and did not contribute to overall morbidity. The IPC patients had fewer
      failures than the systemic medication patients.

PMID- 7638995
TI  - Laparoscopic cholecystectomy: an original three-trocar technique.
AB  - At present, laparoscopic cholecystectomy is the treatment of choice for
      gallbladder stones. The operating technique reported by most authors includes the
      use of four trocars. We report a group of 710 consecutive patients treated by an
      original three-trocar technique. The use of the fourth trocar was necessary in
      only 55 cases (8%). However, among 56 cases of acute cholecystitis the use of the
      fourth trocar was necessary in 14 cases (25%) (p < 0.01). Twenty-six
      laparoscopies were converted to open procedures (3.6%). Four common bile duct
      injuries were observed (0.5%): two of them among the 655 operations with three
      trocars (0.3%) and two after application of the fourth trocar at the beginning of
      the procedure because of dissection difficulties. Our results are similar to
      those using the "classic" four-trocar technique. Moreover, this technique is less
      expensive and allows one less scar.

PMID- 7638996
TI  - Surgery for chronic pancreatitis: what quality of life ahead?
AB  - We attempted to evaluate the quality of life of patients with proved long-lasting
      chronic pancreatitis. We measured the clinical and psychological status of 60
      patients who had undergone various surgical treatments for their disease. The
      presence and severity of depression and other symptoms of distress were assessed,
      as were disease-specific functional and physical problems. Few patients had
      serious conditions, such as pain, malnutrition, or psychoneurotic complaints. The
      relation between depression and the time of onset of symptoms and of surgery
      appeared doubtful, and no statistically significant correlations were found
      between severity of emotional disturbance and other functional characteristics.
      Insulin-dependent diabetes and correlated diseases had the most negative
      influence on everyday well-being. Postoperative follow-up and the need for
      recurrent medical control and care did not lead to negative feelings.

PMID- 7638997
TI  - Resection of the pancreatic head with or without gastrectomy.
AB  - Early and late results of proximal pancreatoduodenectomy were determined in a
      personal and consecutive series of 100 patients (64 men, 36 women, mean age 51.9
      years). Final diagnoses were chronic pancreatitis in 35, idiopathic bile duct
      stricture in 1, carcinoma of the head of pancreas in 27, and other periampullary
      tumors in 37 (duodenal carcinoma 11, ampullary carcinoma 11, neuroendocrine tumor
      10, cholangiocarcinoma 5). Mean follow-up period was 30.5 months (range 3.5-132.0
      months). Resection was conventional (including distal gastrectomy) in 39 patients
      and conservative (retaining the stomach, pylorus, and duodenal cap) in 61
      patients. Resection for inflammatory disease caused greater operative blood loss
      (mean 2.29 versus 1.75 L; p = 0.054) and a longer operative time (6.2 versus 5.2
      hours; p = 0.040) than resection for neoplastic disease. There were four
      operative deaths, two from leakage of the pancreatic anastomosis; another two
      patients survived pancreatojejunostomy leaks. Twenty patients developed
      postoperative complications, seven of whom required reoperation. Good pain relief
      was obtained in 76% of patients with chronic pancreatitis, but five required
      completion distal pancreatectomy at a mean 22.8 months after the first resection.
      Mean survival of patients with pancreatic cancer was 13.2 months. Sixteen
      patients with other periampullary cancers are still alive 41.6 months after the
      operation.

PMID- 7638998
TI  - Outcome of microscopically nonradical, subtotal pancreaticoduodenectomy
      (Whipple's resection) for treatment of pancreatic head tumors.
AB  - From 1983 to 1992 a total of 240 patients with a pancreatic head tumor underwent
      laparotomy to assess the resectability of the tumor. In 44 patients the tumor was
      not resected because of distant metastases (n = 20) or major vascular involvement
      or local tumor infiltration (n = 24) not detected during the preoperative workup.
      A palliative biliary and gastric bypass was performed in these patients. All
      other patients underwent a subtotal (Whipple's resection, n = 164) or total (n =
      32) pancreaticoduo-denectomy. However, in 56 cases after Whipple's resection,
      microscopic examination of the specimen showed tumor invasion in the dissection
      margins. For this reason, these resections were considered palliative. We
      compared hospital mortality, morbidity, and long-term survival of patients who
      had undergone a biliary and gastric bypass for a locally advanced tumor (group A,
      n = 24) with a matched group of patients who had undergone a macroscopically
      radical Whipple's resection that on microscopic examination proved to be
      nonradical (group B, n = 36). Both groups were comparable with regard to age
      (mean 61 years in both groups), duration of symptoms (8 weeks in group A and 10
      weeks in group B), and tumor size (mean 4.25 cm in group A and 4.30 cm in group
      B). Median postoperative hospital stay was 18 days in group A and 25 days in
      group B. Postoperative complications (intraabdominal abscess, gastrointestinal
      hemorrhage, anastomotic leakage, delayed gastric emptying) occurred in 33% of
      patients in group A and in 44% of patients in group B. Hospital mortality was 0%
      and 3% in group A and group B, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7638999
TI  - General rules for recording endoscopic findings of esophagogastric varices
      (1991). Japanese Society for Portal Hypertension.
AB  - The general rules made in 1980 for recording endoscopic findings of esophageal
      varices have widely been used in Japan and in other countries. However, since the
      development of endoscopic sclerotherapy and other modalities of endoscopic
      treatment, these 1980 rules were found to be insufficient for recording mucosal
      changes after treatment. The general rules as revised in 1991 recognize mucosal
      changes such as erosion, ulcer, scar, thrombosed varices, and bleeding signs.
      These new 1991 rules, which seem useful for recording initial evaluation of
      gastroesophageal varices and for describing mucosal changes after sclerotherapy
      as well, are described here.

PMID- 7639000
TI  - Simple, effective procedure with few complications for esophageal varices.
AB  - The surgical morbidity, mortality, and effectiveness of a modified nonshunting
      operation that includes splenic artery division instead of splenectomy,
      devascularization, and esophageal transection (SAD group) were evaluated.
      Eighteen cirrhotic patients with varices who underwent this modified procedure
      were compared with 54 patients treated with a conventional nonshunting operation
      (splenectomy group). Results show that immediate effects on portal pressure and
      preservation of portal perfusion between the two groups were similar. The
      operative time is shorter (p < 0.05), and the bleeding amount is less (p < 0.005)
      in the SAD group than in the splenectomy group. No surgical mortality and no
      major complications were noted in the SAD group. A surgical mortality of 2.3% and
      30% was noted for the elective and emergency operations of the splenectomy group,
      respectively. There was no encephalopathy in the SAD group but one in the
      splenectomy group. Recurrent bleeding occurred in three patients of the
      splenectomy group 1 year after surgery but none in the SAD group. These data
      indicate that this modified procedure is a simple and effective operation with
      few complications for esophageal varices.

PMID- 7639001
TI  - Octreotide for treatment of postoperative alimentary tract fistulas.
AB  - Eighteen patients with postoperative fistulas of the gastrointestinal tract were
      treated with the somatostatin analog octreotide between November 1989 and
      November 1992. Fourteen patients had enterocutaneous fistulas: seven from the
      duodenum and seven from the ileum. Another three patients had pancreatic
      fistulas, and one patient had a biliary fistula. Within 24 hours of octreotide
      treatment, a mean reduction of 52% in the intestinal fistulas' output, 40% in the
      pancreatic fistulas, and 30% in the biliary fistula was noted. In the intestinal
      fistulas group the closure rate was 72% after a mean of 11 days. Early closure
      (mean 6 days) was achieved in all three pancreatic fistulas. In the patient with
      the biliary fistula a 30% reduction was observed twice following the
      administration of octreotide, and an increase occurred when it was withheld. The
      reduction rate of the secretions in high-output intestinal fistulas (> 500
      ml/day) was higher than in the low-output fistulas (63 +/- 8% versus 39 +/- 4%, p
      < 0.05). Fistula output and the initial response to octreotide treatment had no
      value in predicting spontaneous healing. In conclusion, octreotide is a valuable
      tool for the conservative treatment of fistulas of the digestive tract. It is
      especially valuable for management of high-output enteric fistulas and pancreatic
      fistulas.

PMID- 7639002
TI  - Nonfluoroscopic reduction of intussusception by air enema.
AB  - Intussusception is a common pediatric condition in China. Hydrostatic reduction
      with barium sulfate or pneumatic reduction using air and fluoroscopy has become
      the standard method in most centers throughout the world. To avoid radiation
      exposure, reduction without fluoroscopic confirmation was studied. Between 1981
      and 1985 a total of 224 children were diagnosed and treated for intussusception.
      The diagnosis was made correctly on clinical grounds in 184 cases; in 40 cases
      ultrasonography confirmed the clinical diagnosis. Pressurized air reduction was
      successful in 217 patients (96.9%); seven patients required operative reduction.
      Ultrasonograms of the abdomen supported the diagnosis in 40 patients and
      confirmed subsequent reduction. This experience demonstrates that childhood
      intussusception can be reduced using pneumatic pressure without exposing the
      patient to ionizing radiation.

PMID- 7639003
TI  - Impaired liver function and long-term prognosis after hepatectomy for
      hepatocellular carcinoma.
AB  - Patients with hepatocellular carcinoma (HCC) show a wide variety of histologic
      changes in the noncancerous liver parenchyma, and these changes may affect the
      prognosis. In this study, we grouped patients according to the extent of liver
      impairment and investigated their long-term prognosis after hepatectomy for HCC.
      A total of 194 patients were divided into two groups according to their plasma
      clearance rate of indocyanine green (ICG-K) values: those with values < 0.13 min
      1 (group A, n = 97) and those with values of > or = 0.13 min-1 (group B, n = 97).
      Eighty-nine patients with stage I or II HCC were also divided into two groups:
      those with values < 0.13 min-1 (group C, n = 52) and those with values of > or =
      0.13 min-1 (group D, n = 37). Group B patients tended to survive longer than
      group A patients during 4 years after hepatectomy, and group D patients survived
      significantly longer than group C patients (p < 0.01). There was no significant
      difference in the recurrence-free survival rates between those in groups A and B
      or groups C and D. Because patients with poor liver function frequently had
      multiple recurrent lesions and limited therapeutic options, patients with good
      liver function received more intensive treatment. In conclusion, the extent of
      liver impairment is one of the factors determining long-term prognosis after
      hepatectomy for HCC, especially during the early stage of the disease.

PMID- 7639004
TI  - Adjuvant postoperative radiation therapy after curative resection of squamous
      cell carcinoma of the thoracic esophagus: a prospective randomized study.
AB  - Postoperative radiation therapy following curative resection of squamous cell
      carcinoma of the esophagus was investigated in a prospective randomized study. A
      group of 33 patients received postoperative radiation therapy and were compared
      to a control group of 35 patients treated by surgery alone. No statistically
      significant differences were noted between the two treatment groups concerning
      overall and disease-free survival rates. Postoperative irradiation significantly
      increased the incidence of fibrotic strictures of the esophagogastric or
      esophagocolonic anastomoses and caused a delayed recovery of patients quality of
      life. Based on these results, we believe that postoperative radiation therapy
      alone cannot be advocated as a adjuvant therapy following curative resection of
      squamous cell carcinoma of the esophagus.

PMID- 7639005
TI  - Prophylaxis with intraoperative chemohyperthermia against peritoneal recurrence
      of serosal invasion-positive gastric cancer.
AB  - Continuous hyperthermic peritoneal perfusion (CHPP) with a solution which
      contains 30 mg mitomycin C and 300 mg cisplatin has been introduced as a
      prophylactic treatment for peritoneal recurrence after curative resection of 79
      advanced gastric cancers. The control group consisted of 81 patients with
      advanced gastric cancer who underwent curative surgery during the same period.
      CHPP was performed for 60 minutes by perfusing MMC- and CDDP-containing saline
      solutions warmed at 43.5 degrees C by a special CHPP device. In patients with
      pathologically confirmed serosal invasion-positive tumors, the survival rate of
      the CHPP group was significantly higher than that of the control group. A
      survival advantage for stage IV patients was also obtained by CHPP. However,
      there was no survival advantage between the CHPP group and the control group with
      serosal invasion-negative tumors. Adverse effects were observed in four patients
      who underwent CHPP: One developed severe bone marrow suppression, and transient
      hyperazotemia was observed in the other three. There was no difference in the
      incidence of mortality and morbidity between the two groups. These results
      indicate that CHPP is a safe, readily available prophylactic therapy for
      peritoneal recurrence after gastric cancer surgery.

PMID- 7639006
TI  - Early postoperative evaluation of pylorus-preserving gastrectomy for gastric
      cancer.
AB  - Early postoperative evaluation was prospectively performed in 35 gastric cancer
      patients after pylorus-preserving gastrectomy (PPG) between 1989 and 1991,
      comparing the results with those of 29 patients who underwent conventional distal
      gastrectomy (CDG). Surgical stress, including the duration of operation (149.0 +/
      4.3 minutes) and the total volume of bleeding at operation (97.0 +/- 11.2 g),
      was significantly less in the PPG patients. Early postoperative complications
      were seen in 31% after PPG and in 35% after CDG. The most frequent complication
      in PPG patients was remnant gastric stasis (23%). Endoscopy showed redness or
      erosion (or both) of the gastric remnant in 17% after PPG and in 81% after CDG.
      Bile regurgitation was demonstrated in 11% after PPG and in 62% after CDG. In PPG
      patients, the pyloric ring opened and closed during the examination. Gastric pH
      was 4.2 +/- 0.4 in PPG patients but was significantly lower in CDG patients. The
      resting gallbladder area, examined by ultrasonography, demonstrated no changes
      after PPG but was significantly enlarged after CDG (from 11.3 +/- 1.2 cm2 to 15.8
      +/- 1.5 cm2 at 2 weeks). The percentage of the original resting gallbladder area
      at 20 minutes after injection of cerulein increased slightly in PPG patients but
      recovered thereafter, whereas in CDG patients it increased significantly (from
      39.4 +/- 8.3% to 66.7 +/- 9.1% at 2 weeks). No gallstone formation was detected
      throughout the observation period after PPG, whereas after CDG it was detected in
      two patients at 1 year.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7639007
TI  - History of replantation: from miracle to microsurgery.
AB  - Severed body parts, from fingers to extremities, are now being routinely
      reattached at medical centers around the world. The dream of replantation traces
      its rich history from miracles and legends to early laboratory experiments and
      clinical attempts, culminating in today's commonplace procedure.

PMID- 7639008
TI  - Cancer of the stomach: a review of two hospitals in Korea and Japan.

PMID- 7639009
TI  - A rapid test for measuring the infectivity of Yellow Fever vaccine.
AB  - An in-house reference preparation of 17D-204 Yellow Fever vaccine was tested 60
      times using LD50 mouse assay and CCID50 method. The mean virus titre, standard
      deviation and coefficient of variation obtained were comparable. Student's t-test
      indicated that there was a statistically insignificant difference between the two
      methods (p > 0.05) used for potency test with a correlation coefficient of 0.666
      (p < 0.05). CCID50 assay for measuring the infectivity of Yellow Fever vaccine is
      rapid, sensitive and reproducible.

PMID- 7639010
TI  - The influence of gamma inulin and Algammulin on the immune response in sheep to a
      recombinant antigen of Taenia ovis.
AB  - Gamma inulin and Algammulin, two new adjuvants, were examined and compared with
      alum and Freund's Complete/Incomplete Adjuvant (FCA/FIA), for potentiation of
      cell-mediated immunity (CMI) and humoral immunity in sheep to a recombinant
      Taenia ovis antigen. The ability to protect sheep when challenged with live T.
      ovis eggs was also assessed. The results showed that gamma inulin and Algammulin
      induced a CMI response which was comparable to the FCA/FIA and alum groups and
      significantly higher than the control saline group. While gamma inulin,
      Algammulin and alum performed similarly and induced a significantly higher
      humoral immune response than the saline group. FCA/FIA elicited a much higher
      humoral immune response. Algammulin did not show the synergistic effect seen in
      mice and performed similarly to gamma inulin and alum alone. All the adjuvant
      groups induced significantly higher IgG1 and IgG2 levels than the saline group
      and they all favoured IgG1 production. When the sheep were challenged with live
      T. ovis eggs, at 25 weeks after primary immunization, the only group to show
      significant protection was the one which received FCA/FIA.

PMID- 7639011
TI  - The Lyme disease vaccine candidate outer surface protein A (OspA) in a
      formulation compatible with human use protects mice against natural tick
      transmission of B. burgdorferi.
AB  - Development of a vaccine for the Lyme disease spirochete, Borrelia burgdorferi,
      has focused on the bacterial lipoprotein, major outer surface protein A (OspA).
      With few exceptions, testing of OspA vaccines in animal models has involved
      challenge with needle inoculation of cultured spirochetes. Recombinant OspA
      proteins from two OspA divergent strains of B. burgdorferi were tested for their
      vaccine potential in three different strains of mice challenged with laboratory
      reared ticks with a high rate of B. burgdorferi infection. All formulations of
      the B. burgdorferi sensu stricto derived OspA vaccine protected all strains of
      mice when challenged by ticks infected with an OspA homologous strain of the
      spirochete, whereas heterologous OspA from B. afzelii did not protect.
      Furthermore, ticks feeding on protected mice had reduced OspA levels compared to
      unvaccinated controls.

PMID- 7639012
TI  - Quantification of hepatitis B vaccine-induced antibodies as a predictor of anti
      HBs persistence.
AB  - Hepatitis B vaccine-induced antibodies (anti-HBs) were quantified in 35 subjects
      (study group) and in an additional 24-59 subjects (controls) during a period of
      82 months after vaccination against hepatitis B and the values used as a basis to
      develop a logarithmic formula to describe the post-booster antibody kinetics. The
      actual anti-HBs titres are shown to be proportional to the peak titre one month
      post-booster but inversely proportional to the number of months between the time
      of booster and of retesting. Using this model and an anti-HBs quantification more
      than a month post-booster, the individual persistence of vaccine-induced anti-HBs
      antibodies can be calculated.

PMID- 7639013
TI  - Synthesis and characterization of a polyvalent Escherichia coli O-polysaccharide
      toxin A conjugate vaccine.
AB  - A 12-valent Escherichia coli O-polysaccharide (O-PS)-toxin A conjugate vaccine
      was formulated. Nonpyrogenic, low-molecular-weight O-PS was derived from
      lipopolysaccharides (LPS) of the following serotypes: O1,O2,O4,O6,O7,O8,O12,
      O15,O16,O18,O25, and O75. Individual O-PS were covalently coupled to Pseudomonas
      aeruginosa toxin A using adipic acid dihydrazide as a spacer molecule and
      carbodiimide as a coupling agent. On a weight basis, the final multivalent
      vaccine was composed of 43% O-PS and 57% toxin A. The vaccine was nontoxic nad
      nonpyrogenic in anti-LPS immunoglobulin G (IgG) antibody titers. When passively
      transferred to mice, immune rabbit IgG conferred statistically significant (p <
      0.05) protection against a challenge with 9 of the 12 vaccine serotypes. For two
      serotypes, although the mortality rate declined by > or 50% in the passively
      immunized versus the control group, the difference did not reach statistical
      significance. The degree of protection provided by passively transferred IgG was
      influenced by both the anti-LPS antibody levels in the IgG preparation and the
      virulence of the challenge strain. Active immunization of mice with either
      conjugate vaccine or killed E. coli whole cells did not confer protection. This
      was most probably due to the fact that these antigens induced a meagre anti-LPS
      IgG antibody response.

PMID- 7639015
TI  - Protection against ricin intoxication in vivo by anti-idiotype vaccination.
AB  - A BALB/c murine anti-ricin monoclonal antibody (mAb BG11-G2, IgG1K), was recently
      isolated and shown to passively protect syngeneic mice against ricin intoxication
      in vivo. New Zealand White rabbit polyclonal anti-idiotype (anti-Id) antibodies
      were raised to BG11-G2 anti-ricin mAb, and rendered specific by repeated
      absorption over agarose normal mouse immunoglobulin (Ig). The absorbed rabbit
      anti-Id antibodies lost reactivity to normal mouse Ig and to a BALB/c anti-T-2
      mycotoxin IgG1K mAb (HD11), but remained reactive with BG11-G2 anti-ricin mAb.
      The rabbit anti-Id inhibited the binding of BG11-G2 mAb to ricin-coated wells,
      and elicited a specific and protective anti-ricin antibody response in naive
      BALB/c mice. Whereas all mice vaccinated with a control rabbit anti-Id antibody
      preparation died from in vivo ricin challenges, mice immunized with the rabbit
      anti-Id specific for BG11-G2 mAb were protected to various degrees. All mice
      vaccinated with rabbit anti-Id to BG11-G2 and challenged with ricin doses of 35
      and 50 micrograms kg-1 body weight died from the challenge; however, a delay in
      the elapsed time between ricin administration and death was observed in these
      mice as compared to that of the control anti-Id-immune mice. Five of seven mice
      vaccinated with the rabbit anti-Id to BG11-G2 and subsequently challenged in vivo
      with a ricin dose of 20 micrograms kg-1 body weight survived the lethal in vivo
      ricin challenge, whereas all the control mice died.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7639014
TI  - Immune responses and protection against Bordetella pertussis infection after
      intranasal immunization of mice with filamentous haemagglutinin in solution or
      incorporated in biodegradable microparticles.
AB  - The intranasal (i.n.) immunization of mice with Bordetella pertussis filamentous
      haemagglutinin (FHA) either as a solution or incorporated in biodegradable
      microparticles induced very similar immune responses. Both resulted in strong
      systemic IgG responses to FHA and good levels of anti-FHA IgG and IgA in the
      lungs of immunized mice. In comparison, the intraperitoneal (i.p.) immunization
      of mice with FHA, as a solution, engendered anti-FHA antibody responses which
      were stronger for serum IgG, similar for lung IgG and lower for lung IgA. The
      anti-FHA antibody levels, as measured by immunosorbent assay, were shown to
      correlate with their functional activity in the blocking of B. pertussis adhesion
      to HeLa tissue-culture cells. All three forms of immunization appeared to
      stimulate T-cell responses as assessed by in vitro antigen-specific spleen cell
      proliferation and IL-2 secretion indicative of a Th1 type response, however,
      cells from i.p. immunized mice only secreted low levels of IL-5. All three
      methods of FHA immunization provided mice with significant protection against
      subsequent aerosol challenge with virulent B. pertussis. Mice which had been
      immunized intra-nasally eliminated the bacteria from their lungs slightly more
      rapidly than i.p. immunized mice, demonstrating the efficacy of intranasal
      administration of FHA in solution and in the more practical biodegradable
      microparticle form.

PMID- 7639016
TI  - Search for optimal parent for recombinant vaccinia virus vaccines. Study of three
      vaccinia virus vaccinal strains and several virus lines derived from them.
AB  - Three vaccinia virus strains (Praha, DD--a DRYVAX Wyeth vaccine-derived virus-and
      LIVP) were examined for growth in various cell cultures and for virulence and
      immunogenicity in mice. The viruses did not differ by their growth rates in
      monkey kidney cells (CV-1), human diploid cells (LEP), rat TK cells (RAT 2) or
      primary dog kidney cells. The immunogenicity of Praha and DD viruses was similar,
      the virus LIVP was somewhat more immunogenic. In terms of virulence in 3-day-old
      mice, the DD virus was the most attenuated. Single-plaque progenies were derived
      from the original smallpox vaccines VARIE Sevac (strain Praha) and DRYVAX Wyeth
      and tested for the above markers and DNA restriction patterns. The results
      obtained demonstrated biological and molecular heterogeneity of the original
      virus populations. Close linkage was observed between immunogenic activity and
      virulence in 3-day but not in 3-week mice. The results indicate that smallpox
      vaccine preparations may serve as an abundant source of virus mutants.

PMID- 7639017
TI  - Evaluation of the safety, immunogenicity, and efficacy in healthy adults of four
      doses of live oral hybrid Escherichia coli-Shigella flexneri 2a vaccine strain
      EcSf2a-2.
AB  - In previous trials, live invasive Escherichia coli-Shigella flexneri 2a hybrid
      vaccine candidate EcSf2a-2, administered to adult volunteers as 3 doses of ca. 2
      x 10(9) colony forming units (c.f.u.) spaced over one week, induced fever and/or
      diarrhea in 11% of subjects and provided only limited protection (36% efficacy)
      against illness following challenge with virulent S. flexneri 2a. We sought to
      improve the clinical safety of this vaccine by administering a lower inoculum,
      and to enhance protective immunity by administering additional booster doses at 2
      weeks. Twenty-one healthy adults were immunized with ca. 7 x 10(8) c.f.u. of
      EcSf2a-2 on days 0, 3, 14, and 17. The vaccine consistently colonized the
      intestine without causing serious adverse reactions; mild diarrhea developed in
      one subject and low grade fever in another. Vaccination elicited an antibody
      secreting cell (ASC) response to lipopolysaccharide (LPS) in all subjects, which
      was highest on day 7 and notably diminished thereafter on days 10, 16, 21, and
      24, suggesting that active mucosal immunity developed rapidly. The magnitude of
      the response was modest (geometric mean peak = 16 IgA ASC/10(6) peripheral blood
      mononuclear cells) and an IgG serological response to LPS was detected in only
      19% of subjects. Following experimental challenge with virulent S. flexneri 2a
      administered with bicarbonate buffer, shigellosis (diarrhea, dysentery, or fever)
      developed in 10 of 16 vaccine recipients (63%) and in 12 of 14 unvaccinated
      controls (86%), resulting in a vaccine efficacy of 27% (95% confidence limits 
      197, 82, p = 0.15, 1-tailed).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7639019
TI  - Anaesthesia in Papua New Guinea: an ethnological viewpoint.

PMID- 7639020
TI  - Maintenance of clinical standards of anaesthetists.

PMID- 7639021
TI  - A choice of techniques--or techniques of choice?

PMID- 7639018
TI  - Effect of DETOX as an adjuvant for melanoma vaccine.
AB  - The identification of effective adjuvants is critical for tumor vaccine
      development. Towards this end, we examined whether the immunogenicity of a
      melanoma vaccine could be potentiated by DETOX, an adjuvant consisting of
      monophosphoryl lipid A (MPL) and purified mycobacterial cell-wall skeleton (CWS).
      Nineteen patients with resected stage III melanoma were immunized with a
      polyvalent melanoma antigen vaccine (40 micrograms) admixed with DETOX, q3 wks x
      4. Seven patients received vaccine + low-dose DETOX (10 micrograms MPL + 100
      micrograms CWS) and 12 received vaccine + high-dose DETOX (20 micrograms MPL +
      200 micrograms CWS). A non-randomized control group of 35 patients was treated
      similarly with 40 micrograms vaccine + alum. One week after the fourth vaccine
      immunization, melanoma antibodies were increased over baseline in 7/7 (100%)
      patients treated with vaccine + low-dose DETOX, 8/12 (67%) patients treated with
      vaccine + high-dose DETOX, and in 4/19 (21%) of vaccine + alum patients. For the
      entire DETOX group, the antibody response rate was 15/19 (79%) compared 4/19
      (21%) in the alum group (p < 0.001). In contrast, a strong delayed-type
      hypersensitivity (DTH) response (> or = 15 mm increase in DTH response over
      baseline) was induced in 50% of the entire DETOX group versus in 47% of the alum
      group. Median disease-free (DF) survival for the entire DETOX group was 17.8
      months compared with 32.1 months in the alum group (p < 0.05). In conclusion,
      DETOX markedly potentiated antibody but had little effect on DTH responses to
      melanoma vaccine immunization. It did not appear to improve disease-free survival
      in comparison to alum in this non-randomized study.

PMID- 7639022
TI  - Comparison of conventional anaesthesia, total intravenous ketamine and epidural
      block for abdominal hysterectomy.
AB  - Techniques of total intravenous anaesthesia with ketamine and continuous epidural
      block are compared with the conventional method of using halothane, nitrous oxide
      and relaxant. Both ketamine and epidural techniques were associated with minimal
      cardiovascular disturbances, low blood loss and better quality of anaesthesia and
      recovery scores. The usual psychomimetic effect associated with ketamine
      administration was observed in only one patient. Further experience of total
      intravenous ketamine anaesthesia with adjunctive use of fentanyl to attenuate
      cardiovascular effects and midazolam for the pyschomimetic effect can further
      refine the technique. Cerebral function monitoring, if possible, will allow
      correlation of depth of anaesthesia with drug dosage and can ensure appropriate
      anaesthetic depth and recovery.

PMID- 7639023
TI  - Pain clinic in Goroka Base Hospital: a retrospective analysis.
AB  - Over a nine-month period in Goroka Base Hospital 310 patients with chronic pain
      were treated in the pain clinic. Disabling lower backache was the most common
      complaint, followed by myofascial disorders and cancer pain. Best results for the
      management of pain was observed in patients receiving intralesional steroids,
      followed by intercostal block and lumbar sympathetic block for abdominal
      malignancies.

PMID- 7639024
TI  - A review of analgesia for knee surgery.
AB  - This review demonstrates that there are inadequate data to draft a protocol in
      pain management after knee surgery. The review is intended to provide a stimulus
      for those who manage their orthopedic patients in a particular manner to test
      their pain management strategy in a random, prospective, controlled manner. They
      should aim to provide a data base that will assist in solving the knee surgery
      conundrums which inhibit identification of the most efficacious delivery of
      analgesia.

PMID- 7639025
TI  - Induced hypotension in a smoker.
AB  - An episode of hypoxia following the use of propranolol and sodium nitroprusside
      to induce hypotension in a 50-year-old male patient undergoing craniotomy for
      frontal meningioma is described. The importance of proper preoperative screening
      of lung function and intraoperative monitoring of blood gases is highlighted.

PMID- 7639026
TI  - Chronic pain management: the role of the anaesthetist.
AB  - World-wide more than 4 million people are at present suffering from cancer pain,
      and many more from other kinds of pain. Pain remains an under-treated and
      neglected public health problem. Lately technological advances and greater
      understanding of the physiology and anatomy of pain have helped further progress
      in pain management but much is still empirical without a scientific basis. Since
      the fundamental component of the practice of anaesthesiology in the treatment of
      pain, the anaesthetist is the best person to understand pain and organize pain
      clinics.

PMID- 7639027
TI  - The perioperative management of diabetic patients undergoing surgery.

PMID- 7639028
TI  - [Can selective decontamination of the digestive tract as a routine procedure on
      intensive care units be recommended?].
AB  - After giving an overview on the epidemiological and microecological background,
      the applicable drugs, and the necessary microbiological surveillance for
      Selective Decontamination of the Digestive tract (SDD), the results of 2 new
      metaanalyses of 22 and 25 individual randomized studies are discussed. A 50%
      reduction of the pneumonia incidence results in an only marginal reduction of the
      mortality rate in the subgroup of topically plus for the first few days
      systemically treated patients in mixed intensive care units. Facing the weak
      prognostic relevance of ventilator pneumonia, the reduction of microbial
      translocation from the lower GI tract as a major goal for SDD is discussed. The
      chance and the need to confirm a mortality benefit in multicentre trials
      enrolling large numbers of homogeneous surgical patients are explained. At the
      present time, SDD as a routine can not (yet) be recommended.

PMID- 7639029
TI  - [Current trends in clinical urology].
AB  - Many recent developments in urologic diagnostic and therapy are also of interest
      for general surgeons. Flexible and semirigid ureteroscopes (6-8 F) provide easy
      and atraumatic access to the whole upper urinary tract. Beside extracorporeal
      shockwave-lithotripsy now various endourologic modalities to treat ureteral
      stones are available. Although useful, laparoscopic techniques are not yet widely
      accepted by urologists because there is a lack of indications in urologic
      laparoscopic surgery. The functional reconstruction of the urinary bladder by
      means of an ileal neobladder with an anastomosis to the urethra in the male or
      with a continent stoma and selfcatheterism provides better quality of life in
      patients after radical cystectomy. Nephron-sparing tumor surgery may become a
      routine procedure under certain precautions such as small tumor size, patient's
      compliance and good local medical infrastructure. Especially for urologic
      microsurgery, neurourology and different treatments of benign prostatic
      hyperplasia essential new and interesting improvements are expected.

PMID- 7639030
TI  - [Cause of death after liver transplantation: an analysis of 41 cases in 382
      patients].
AB  - The aim of this study was to analyse the causes of death after liver
      transplantation in order to find and to avoid preventable fatal complications if
      possible. METHODS: Between September 1988 and September 1993 415 orthotopic liver
      transplantations in 382 patients were performed at the Rudolf Virchow University
      Hospital in Berlin. During the same interval 41 (10.7%) of these patients died.
      Their clinical records were reviewed. RESULTS: The main cause of death was
      infection (29.3%), followed by recurrent malignancy (21.9%). Less patients died
      because of hepatitis B-reinfection (14.6%), chronic rejection (7.3%), hemorrhage
      (7.3%), cardiac failure (7.3%), trauma (4.8%), hypoxia (4.8%) and recurrence of
      alcoholic liver disease (4.8%). There was a wide spectrum of opportunistic
      infectious agents with CMV and Pneumocystis carinii being the most important
      pathogenic organisms. Only one isolated bacterial infection as principle cause of
      death was found. In all fatal infections the lung was the primary site of
      infection, 7 patients additionally developed sepsis. Altogether 75 patients
      (19.6%) with hepatitis B-cirrhosis were transplanted. Six of them (8%) developed
      a fatal hepatitis B-reinfection. Malignancy was the indication for OLT in 41
      patients (10.7%). Six of these patients (14.6%) died because of recurrent tumor.
      Regarding the whole series, most deaths occurred four to twelve months (58.5%)
      and only five (12.2%) during the first month after OLT. CONCLUSION: Recurrence of
      primary disease is an important factor regarding total mortality. Therefore it is
      necessary to practise a careful selection of liver transplant recipients. In the
      future more attention needs to be drawn towards prevention, identification and
      management of opportunistic infections.

PMID- 7639031
TI  - [Arterial complications after liver transplantation].
AB  - Disturbances of the arterial perfusion of the graft following liver
      transplantation (LTx) are mainly of technical origin and contribute considerably
      to the postoperative morbidity and lethality. Aim of this retrospective survey
      was to determine the incidence and the consequences of hepatic artery thrombosis
      (HAT) and stenosis (HAS) in 203 patients (pts.) who underwent 246 liver
      transplantations. HAT was identified in 22 pts. by clinical, laboratory and
      sonographic and/or angiographic means. In 4 pts. HAT was asymptomatic and was
      detected during routine examination. Two pts. underwent immediate
      retransplantation, of which only one survived. Primary revascularization was
      performed in 16 pts., but was successfully only in 5 pts. Six pts. eventually
      underwent retransplantation with only one survivor. Biliary complications after
      HAT were observed in 10 pts. (45%), presenting in 8 pts. as biliary leak, in 2
      pts. as bile duct stenosis. In the 12 patients with HAT who died the leading
      causes of death were sepsis (n = 3) and multiple organ failure (n = 3). HAS was
      observed in 11 pts., of which one was asymptomatic. Ten pts. underwent surgical
      revision. Redo of the arterial anastomosis was the most common procedure. Four
      pts. survived long term. Biliary tract complications were seen in 3 pts. (leak 1,
      stenosis 2). Three pts. died secondary to HAS from sepsis. These results confirm
      the life threatening character of any arterial complication after LTx. Because
      other reasons are rarely detected, the majority is attributable to technical
      faults. In order to avoid arterial complications extraordinary care has to be
      taken in the surgical handling of the arterial supply of the graft during
      harvesting, back table work and transplantation.

PMID- 7639032
TI  - [Effect of anastomosis reconstruction on vascular complications after liver
      transplantation].
AB  - AIM: Besides primary non function (PNF), vascular complications are responsible
      for the majority of early surgical and interventional therapy following liver
      transplantation. The purpose of this study was to evaluate the influence of the
      variety of arterial anastomosis on postoperative morbidity and mortality. METHOD
      USED: In 179 liver transplantations, vascular (arterial and portal) complications
      within the first 3 months were analyzed with respect to the type of
      reconstruction. The arterial anastomoses were divided into 3 groups according to
      the recipient artery used [Group (I): common hepatic artery (CHA), (II): hepatic
      artery (HA), (III): aorta]. For statistical analysis comparison of two
      proportions and the logrank test were used. RESULTS: The reconstruction was done
      primarily to the recipient CHA (69%, n = 124), less often to the HA (15%, n = 26)
      or directly to the aorta (16%, n = 29). The portal anastomosis-with the exception
      of two cases (dacron graft and internal iliac vein interposition)-was always end
      to end and resulted in four reinterventions (2.2%, kinking: n = 1, thrombosis: n
      = 3). Arterial complications (11.7%) like thrombosis, stenosis and dissection (n
      = 17), bleeding (n = 2) and steal phenomenon (n = 2) occurred more frequently.
      The difference in one year survival between patients with (n = 12/25, 47%) and
      without (n = 42/53, 79%) vascular complications was significant (chi 2 = 4.72, FG
      1, logrank test p < 0.05). CONCLUSION: The rate of complications causing surgical
      or interventional therapy is independent of the choice of arterial
      reconstruction. The one year survival rate in patients with vascular
      complications is significantly decreased.

PMID- 7639033
TI  - [Therapeutic approach to hemobilia].
AB  - AIM OF THE STUDY: Hemobilia, defined as hemorrhage arising from pathological
      changes in the biliary tract, represents a rare entity. In a retrospective study
      the presentation, diagnosis, and management of hemobilia were investigated.
      PATIENTS AND METHODS: Since January 1991 six patients suffering from severe
      hemobilia presented to our department. Jaundice, right upper quadrant abdominal
      pain, hematemesis and melaena were the most frequent symptoms leading to
      admission. Hemobilia originated from iatrogenic injury following percutaneous
      liver biopsy and endoscopic removal of common bile duct stones, and malignant
      hepatic or biliary tumors. Duodenoscopy revealed bleeding from the papilla in all
      patients. Diagnosis was confirmed by ERCP in all patients and angiography in 5 of
      6 patients. RESULTS: Angiographic occlusion of an arterial lesion with coils was
      successfully achieved in one patient. One patient was treated conservatively. In
      3 patients liver resections were performed to control bleeding and the underlying
      tumorous pathology. In another patient, operative ligation of the supplying
      artery had to be performed. Within a minimum follow-up of six months none of the
      six patients showed recurrence of hemobilia. CONCLUSION: Considering the impact
      of etiologic, diagnostic and therapeutic aspects in treatment of hemobilia we
      suggest an algorithm for a rational approach to hemobilia. Angiographic occlusion
      may control the bleeding and improve the patient's general condition. Definitive
      surgical treatment of hemobilia is safe and effective.

PMID- 7639034
TI  - [Is liver abscess still an indication for liver resection?].
AB  - AIM: The standard therapy for liver abscesses consists of percutaneous drainage.
      In certain cases a liver resection may be indicated. The indication for liver
      resection in six patients with liver abscess is analysed retrospectively.
      METHODS: Between 7.7.87-13.10.93 six patients (4 male, 2 fem.) in the age of 40
      72 years (mean 59 yrs.) underwent liver resection for liver abscess at our
      institution. The patients suffered from symptoms of a progressive liver abscess
      formation: fever, hepatomegaly, loss of weight, jaundice and anorexia. Abscess
      localization was performed preoperatively by ultrasound and CT. Drainage attempts
      were unsuccessful in these patients, resections were carried out for suspicion of
      malignancy or during a laparotomy due to other reasons. RESULTS: Liver resections
      were left and right hemihepatectomy (1x each), left lateral resection (3x) and
      one wedge resection. Intraoperative blood transfusion requirements were not
      different from those of other indications for resection. Postoperative
      hospitalization lasted 12-33 days (mean 19 days). The postoperative course was
      uneventful, in one case a hematoma at the resection site required drainage.
      CONCLUSION: Resection for liver abscesses is indicated only in exceptional cases
      but allows for definite therapy.

PMID- 7639035
TI  - [Bile duct injuries after laparoscopic cholecystectomy].
AB  - Injuries to the extrahepatic bile duct present a severe complication in
      laparoscopic cholecystectomy occurring in 0-2.6%. From June 1991 to September
      1994 four patients were treated to the Department of Surgery at Bonn University
      with bile duct injuries after laparoscopic cholecystectomy. All had complete
      sections of the common bile duct. They were treated twice with a biliodigestive
      anastomosis and once by direct suturing of the d choledochus. One of our own
      patients suffered an injury of the right hepatic duct, most probably due to a
      thermic lesion. In all cases anatomy was irregular or unclear. To avoid these
      complications an intraoperative cholangiography should be performed in these
      situations. The reconstruction after inadvertent injuries of the bile duct
      depends on the localisation and the age of the lesion.

PMID- 7639036
TI  - [Effect of various methods of resection of the stomach in liberation of
      cholecystokinin, neurotensin and on pancreatic function].
AB  - In a follow up study 19 patients after Billroth-I, 22 patients after Billroth-II
      resection and 38 patients after total gastrectomy (23 with Roux-Y-reconstruction
      and 15 with Longmire-Gutgemann) underwent a stool fat determination and an
      indirect pancreatic function test with fluorescein dilaurate in serum und urine.
      In 9 of 19 cases (47.3%) after B-I-resection and 14 of 22 patients (63.5%) after
      B-II-resection there were pathological results of the PLT-test in urine. After
      total gastrectomy as well with reconstruction of the duodenal passage as with its
      exclusion the PLT-test results were pathological in 60% resp. 87%. These results
      indicate a secondary pancreatic insufficiency following gastric resection.

PMID- 7639037
TI  - [Graft-vs.-host reaction: a severe complication after orthotopic liver
      transplantation].
AB  - INTRODUCTION: Patients with solid-organ transplantation are at risk for Graft
      versus-host disease (GVHD) even though GVHD is a rare phenomenon after orthotopic
      liver transplantation (OLT). CASE REPORT: The 30 yrs old male patient received an
      ABO compatible orthotopic liver graft for acute liver failure due to intoxication
      with amanita phalloides. Twenty-four days after OLT the patient developed high
      temperatures up to 40.0 degrees C and pancytopenia and was treated for CMV
      infection. On postoperative day (POD) 32 an erythematous maculo-papular rash
      developed. A drug induced toxic epidermal necrolysis was suspected and treated
      with plasmapheresis for three days. Acute renal failure and respiratory
      insufficiency occurred while liver function was not impaired. A skin biopsy at
      that time showed no specific signs for GVHD. On POD 42 HLA-typing of circulating
      lymphocytes presented donor HLA phenotype and GVHD was established. Therapy with
      ATG was started but the clinical status of the patient did not improve. Following
      administration of OKT3 on POD 48 a reduction of activated CD-3 lymphocytes from
      90% to 60% could be achieved. Due to the low platelet count the patient died of
      intracerebral hemorrhage on POD 52. CONCLUSION: Since a fully developed GVHD is
      rare after OLT and the similarity of the clinical findings to viral or drug
      induced diseases is high, diagnosis is often made late in the course of the
      disease. Furthermore, therapeutic measures for GVHD are scarce and diagnosis has
      to be established as early as possible, hence pretransplant procurement of donor
      and recipient mononuclear cells for later study should be considered to decrease
      the time period between clinical suspicion and diagnosis.

PMID- 7639038
TI  - [Induction of impaired hepatic microcirculation by in situ hilus preparation in
      liver explantation].
AB  - AIM: Usually, in-situ preparation of the hepatic hilar structures is performed
      prior to the perfusion with preservation solution. Aim of this study was to
      investigate mechanical effects of liver preparation on the hepatic
      microcirculation. METHODS: 16 pigs (German landrace) were randomized in two
      groups. In both groups, laparotomy was performed after intratracheal intubation.
      Subsequently, a thermal diffusion probe was implanted into the medial left liver
      lobe for quantification of microperfusion. In group A (n = 8), bile duct, hepatic
      artery, and portal vein were exposed and the lesser omentum transsected
      thereafter. Ultrasound-volume-probes were placed around the hepatic artery and
      portal vein. Simultaneous measurement of hepatic microperfusion and total liver
      blood flow was performed five minutes after the end of liver preparation. In
      group B (n = 8) hepatic microperfusion was quantified 45 minutes after laparotomy
      without further manipulations. RESULTS: By the preparation, liver perfusion was
      significantly reduced in group A from 78 +/- 13 ml/100g/min to 61 +/- 16
      ml/100g/min. After preparation a total liver blood flow of 137 +/- 46 ml/100g/min
      was recorded indicating a shunt fraction of 51 +/- 21%. In contrast, hepatic
      microperfusion in group B remained at baseline during the whole observation
      period (79 +/- 3 ml/100g/min vs. 78 +/- 5 ml/100g/min). CONCLUSION: In-situ liver
      preparation induces a relevant disturbance of hepatic microcirculation.
      Preservation perfusion shortly after surgical manipulation could become
      ineffective because of an increase in shunt flow. If the regeneration period is
      too short, e.g. lack of heart explantation, the quality of the liver graft could
      be limited.

PMID- 7639039
TI  - [Is ion-selective measurement of the liver surface for detection of cell damage
      suitable?--A study of the rat liver transplantation model].
AB  - Aim of the study is to detect a reperfusion injury in rat liver transplantation
      by the Ion-selective Surface-Measurement (OMS). METHODS: Lewis rats served as
      models for 30 liver transplantations with 1, 6 or 12 hrs of cold ischemia
      respectively. Directly before, during and after transplantation potassium- and
      hydrogen-concentrations were measured with the OMS and compared to transaminase
      values on day 1, 3 and 7 as well as to biopsies on day 3. RESULTS: Transaminase
      values and histology show ischemic cell injuries correlating to the length of
      ischemia, whereas potassium- and hydrogen-concentrations on the organ surface do
      not. CONCLUSIONS: Ischemic cell injury in the rat liver cannot be detected by the
      Ion-selective Measurement.

PMID- 7639040
TI  - [Comments on the contribution "Benefit-risk assessment of surgical treatment of
      asymptomatic carotid lesions" (G. Hohlbach and R. Meffert)].

PMID- 7639043
TI  - [Spontaneous brain abscess--bacteriology, therapy and prognosis].
AB  - Spontaneous intracranial abscesses are quite rare in western industrial
      countries. According to the recently published papers, each neurosurgical centre
      is expecting 2 to 4 cases a year. Whereas in the last three years we only
      operated on one or two cases a year we treated 8 cases in the first ten months of
      1994. Although this remarkable increase is not statistically significant, further
      observations seem to be indicated. In 5 cases the origin of the abscess remained
      unknown. 3 patients had odontogeneous focuses, 2 middle ear and 2 pulmonary
      infections. One patient was operated on for spontaneous liver abscess few days
      before. Streptococcus was found in 9 cases, Bacteroides, Nocardia and Rhodoturola
      in 1 case each. For one patient no pathogen could be detected. In regard of our
      results, minimal invasive neurosurgical aspiration of the abscess with adjacent
      longterm antibiotic therapy gives a good prognosis with little morbidity. In
      contrast the mortality rate rises if diagnostic procedures are delayed or if the
      detected microorganism is highly resistant to current antibiotics.

PMID- 7639042
TI  - Parafalxial empyemas (two cases).
AB  - Intracranial infections can locate at anywhere in the brain. Subdural empyemas
      are the less common type of intracranial infections, and parafalxial localization
      is seen rare. Findings of intracranial pressure increase developed in a cases who
      were treated for purulent meningitis. Parafalxial empyemas were diagnosed in
      succeeding cranial computed tomography. Middle line was drained by means of
      craniotomy or burrhole. We reported two cases who recovered without any
      postoperative sequel considered the rare localization site of infection.

PMID- 7639041
TI  - Typical interhemispheric subdural haematomas and falx syndrome: four cases and a
      review of the literature.
AB  - Typical Interhemispheric Subdural Haematomas (ISDHs) are located along the whole
      interhemispheric fissure. In the four cases of our series, three of which
      surgically treated, and in the 29 cases reported in literature ISDH has been
      usually encountered in elderly age (mean age 56) in most of cases following head
      injury. Anticoagulant therapy was a favouring factor. The source of bleeding was
      never demonstrated at surgery, nevertheless some authors report a parafalcic
      bridging-veins laceration due to a brain linear acceleration during trauma, as
      cause. Clinically, immediate loss of consciousness was usually absent. Focal
      symptoms arose within 8-48 hours after trauma. In the majority of cases with
      ISDH, focal symptoms have been characterized by controlateral motor palsy with
      crural dominance as it has been observed in the "falx syndrome". Facial palsy was
      absent in all cases but one. Skull fractures were rare. On CT scan ISDH was shown
      as a spontaneously high density parafalcic area in a flat-convex lenticular
      shape. In the only case studied with MRI, the site where the ISDH emerged at
      brain convexity from the interhemispheric fissure, has been clearly localized by
      means of multiplanarity reconstructions, allowed us a target surgical approach.
      The majority of patients underwent surgery. The overall mortality rate was 24%:
      14% among the 7 cases conservatively treated and 27% among the 26 operated ones.
      These last patients had a good recovery in 58% and an improvement in 15%.
      Surgical treatment must be promt as much as possible because of the possible
      sudden worsening of patient clinical conditions. Craniotomy is the surgical
      treatment that achieved the best results, nevertheless in our opinion the
      additional data offered by MRI may repropose the use of target cranial burr
      holes.

PMID- 7639044
TI  - [Cerebral space-occupying lesion in thrombocytosis].
AB  - We report a case of venous thrombosis presented as ischemic intracranial
      expanding lesion localized in the parietal lobe of a young man with essential
      thrombocytosis. As surgical intervention became necessary we were able to
      investigate the morphological changes by histology and immunocytochemistry. The
      almost exclusive venous manifestation of thrombosis most probably initiated by
      elevated amounts of platelets suggests altered blood flow conditions as the
      predominant factor. Surgical interventions in such conditions are rare and might
      only proceed in space-occupying lesions with clinical symptoms. Treatment with
      inhibitors of platelet aggregation under strict control of the patient is the
      therapy of choice.

PMID- 7639045
TI  - [Autonomic dysfunction and the development of secondary brain death syndrome].
AB  - Vegetative disturbances were observed in 88 out of 102 patients, 86%, after a
      primary brain lesion during onset of brain death. Tachycardia was most common in
      64%, hypotonia below 80 mm Hg and hypertonia above 170 mm Hg were present in
      about half of all cases. Hyperthermia above 40 degrees C was noted in 25%,
      hypothermia below 36 degrees C was observed in 31%. The kind of underlying brain
      lesion had no regular influence on the vegetative disturbances. In 5 out of 6
      younger patients these disturbances were less pronounced.

PMID- 7639046
TI  - Intra-extradural hemangioblastoma of the cauda equina.
AB  - This is a case report of a hemangioblastoma of the cauda equina with intra
      extradural extension in the form of a dumbbell tumor. For the first time
      diagnosis of an intra-extradural spinal hemangioblastoma was made by computerized
      tomography (CT) and magnetic resonance imaging (MRI). A total excision was
      performed with microneurosurgical techniques and application of Nd:YAG laser.
      Clinical appearance, neuroradiological diagnostic procedures and neurosurgical
      therapy of intra-extradural hemangioblastomas of the cauda equina and of spinal
      hemangioblastomas of other localization were compared.

PMID- 7639048
TI  - [Bilateral carpal tunnel syndrome--surgical therapy--prognostic factors and
      results].
AB  - Patients submitted to bilateral section of the transverse carpal ligament suffer
      from predisposing diseases, hormonal alterations or have wrists exposed to
      increased occupational strain more frequently than patients with unilateral
      carpal tunnel syndrome. In addition, in this group of patients the results of
      neurophysiological tests are more markedly pathologic. The good initial operative
      results are frequently followed by a relapse of symptoms. There is no appreciable
      difference between the operative results for the right versus for the left hand
      nor between the hand operated on in the first versus in the second place. A long
      term improvement of opposite side symptoms following the first operation only
      occurs in exceptional cases.

PMID- 7639047
TI  - [Type 2 neurofibromatosis without acoustic neuroma].
AB  - Bilateral vestibular schwannomas (VSs) are the hallmark of neurofibromatosis type
      2 and the crucial criteria for the diagnosis of this autosomal dominant disorder
      according to the criteria of the National Institutes of Health Consensus
      Statement. We describe three patients without VSs aged 47, 52 and 69 years, in
      whom a NF2 gene carrier status was diagnosed by spinal tumors, a cataract and
      schwannoma of cranial and peripheral nerves. In one case the diagnosis was
      ascertained by mutation analysis, which revealed a 163bp deletion in the NF2
      cDNA, and by the fact that two daughters had the same deletion and NF2 according
      to the NIH criteria. Our finding suggests that patients with spinal tumors,
      multiple brain tumors, associated neurinomas or cataract might be carriers of a
      mutated NF2-gene. The study suggests that the NIH criteria are too restrictive,
      since NF2 seems to show up for a broader spectrum of phenotypes.

PMID- 7639049
TI  - Mantle-cell lymphoma in a patient with human immunodeficiency viral infection.
AB  - Rare cases of low-grade lymphomas have been described in patients with human
      immunodeficiency virus (HIV) infection. However, this is the first reported case
      of mantle-cell lymphoma, a type of low-grade lymphoma, in a patient who also had
      HIV infection. Salient clinical features included lymphocytosis, lymphadenopathy,
      splenomegaly, and involvement of the bone marrow and meninges. The disease proved
      to be unusually aggressive and response to chemotherapy was insignificant. The
      patient survived only 4 months.

PMID- 7639051
TI  - Human herpesvirus 6 infection associated with hemophagocytic syndrome.

PMID- 7639050
TI  - Sickle cell anemia identified in a multiple-transfused patient through analysis
      of mRNA with an RT-PCR-based technique.
AB  - We report the identification of an Hb S homozygosity in a 29-year-old multiple
      transfused patient with severe kidney disease using a new reverse-transcription
      polymerase chain reaction (RT-PCR) technique with mRNA as starting template. The
      procedure requires considerably less time than sequencing of genomic DNA and is
      recommended for use in the diagnosis of Hb S and other hemoglobinopathies.

PMID- 7639052
TI  - 9th Symposium on Molecular Biology of Hematopoiesis and Treatment of Leukemias
      and Lymphomas. Genoa, June 23-27, 1995. Abstracts.

PMID- 7639053
TI  - Demonstration of thymopoietin transcripts in different hematopoietic cell lines.
AB  - We have cloned and characterized the human thymopoietin (TP) coding region and
      studied the mRNA expression of this gene in different hematopoietic cell lines.
      The 150-bp PCR fragment that encodes the 49-amino-acid human TP peptide was
      isolated from genomic placental DNA. Its colinearity with the cDNA sequence
      suggests lack of introns within the coding region. TP mRNA expression was
      demonstrated in lymphocytes from all the differentiation stages investigated, as
      well as in a myeloid cell line (K-562). These findings suggest a further
      expansion of the proposed TP functions.

PMID- 7639054
TI  - Effects of interleukin-1 and tumor necrosis factor on megakaryocytopoiesis:
      mechanism of reactive thrombocytosis.
AB  - We studied the effects of interleukin-1 (IL-1) and tumor necrosis factor (TNF) on
      mouse megakaryocytopoiesis to evaluate the role of these cytokines in reactive
      thrombocytosis associated with inflammation. Injections of IL-1 or TNF to mice
      induced a significant increase in the megakaryocyte progenitor cell (CFU-Meg)
      count in the spleen. When IL-1 and TNF were injected simultaneously, the splenic
      CFU-Meg count was remarkably increased compared with mice injected with either IL
      1 (p < 0.003) or TNF (p < 0.001) alone. On the other hand, neither IL-1 nor TNF
      showed any megakaryocyte-potentiating or -stimulating effects in vitro. In the
      sera obtained 4 h after administration of IL-1, TNF or both, high megakaryocyte
      potentiating activities were found. Furthermore, an extremely high level of IL-6
      was detected in the serum after administration of both IL-1 and TNF. These
      results strongly suggest that IL-1 and TNF stimulate megakaryocytopoiesis
      indirectly via other cytokine(s) induced from accessory cells, and that increased
      levels of IL-1 and TNF play important roles in the development of reactive
      thrombocytosis caused by inflammation.

PMID- 7639055
TI  - Chronic idiopathic thrombocytopenic purpura in the elderly.
AB  - From a group of 118 patients with chronic idiopathic thrombocytopenic purpura
      (ITP), 43 were older than 60 years at diagnosis. In this report, we describe the
      clinical evolution and therapeutic response in young and old patients. The overal
      rate of hemorrhagic manifestations was similar in the two age groups, but a
      greater risk for severe bleeding was observed in elderly patients. There were no
      significant differences between old and young patients in response to steroids.
      In none of our patients was mortality associated with bleeding or side effects of
      the treatment. In conclusion, we have observed a more benign clinical course in
      elderly patients with chronic ITP as compared to previous reports.

PMID- 7639056
TI  - Small intestinal perforation due to cytomegalovirus infection in patients with
      non-Hodgkin's lymphoma.
AB  - We describe two patients with non-Hodgkin's lymphoma (NHL) who suffered
      cytomegalovirus (CMV)-related small intestinal perforations during the course of
      chemotherapy. Surgical specimens from both patients revealed histologic evidence
      of occlusive vasculitis and tissue destruction caused by CMV-affected cells in
      the submucosa and muscular walls, that may have played an important role in the
      pathogenesis of these perforations. Although such intestinal perforations are
      rare complications in NHL patients, CMV infection should be recognized as a
      primary etiological factor in acute abdominal crises when treating NHL patients
      with pharmaceutical agents including steroids. Emergency surgery and the anti-CMV
      agent, ganciclovir, would improve the prognoses of such patients.

PMID- 7639058
TI  - Serum and urinary manganese levels in patients with Parkinson's disease.
AB  - To elucidate the possible role of manganese in the risk of developing Parkinson's
      disease (PD), we compared serum levels of manganese, and 24-h manganese excretion
      by urine in 29 PD patients and in 27 matched controls. We also measured chromium
      and cobalt in the same samples. All these values did not differ significantly
      between the groups, they were not influenced by antiparkinsonian drugs, and they
      did not correlate with age, age at onset and duration of the PD, scores of the
      Unified PD Rating Scale or the Hoehn & Yahr staging in the PD group. These
      results might suggest that serum levels and urinary excretion of manganese are
      apparently unrelated to the risk of developing PD.

PMID- 7639057
TI  - Geographical variations in mortality from Parkinson's disease in Japan, 1977
      1985.
AB  - Geographical variations in the age-adjusted death rate from Parkinson's disease
      (PD) were analyzed using Japanese vital statistics for 1977-1985. The highest age
      adjusted PD death rate was 2.7 times higher in Tottori (2.9 per 100,000
      population aged 25 years and over) than Fukushima (1.1) prefectures. The overall
      age-adjusted PD death rate was 1.8. The age-adjusted PD death rate was higher in
      urban (2.0) than in rural (1.7) areas during the period 1979-1985. The age
      adjusted PD death rate was higher in the southwest than in the northeast.
      Correlation coefficients between the age-adjusted PD death rate, and the mean
      physician-population ratio and the mean neurologist-population ratio were
      positive, but not statistically significant. The regional variations in the age
      adjusted PD death rate were not entirely explained by the availability of medical
      facilities. Environmental risk factors for PD might differ regionally. Further
      investigation is needed to explain the differential age-adjusted PD death rate in
      Japan.

PMID- 7639059
TI  - Multiple sclerosis in the Faroe Islands: transmission across four epidemics.
AB  - As of 1991 we had ascertained 42 native resident Faroese plus 12 non-resident
      "migrant" Faroese with clinical onset of MS in this century. The resident series
      comprised four successive epidemics beginning in 1943 and then at 13-year
      intervals thereafter, a separation of very high statistical significance (p <
      0.00001). We concluded that the first epidemic in the Faroes resulted from the
      introduction of a specific but unknown infection which we call the "primary MS
      affection" (PMSA) by occupying British troops during World War II. Clinical
      neurologic MS (CNMS) is then the rare late sequel of infection with PMSA. The
      first epidemic defined age of susceptibility to PMSA as age 11 to 45 at onset of
      exposure. Models of transmission used for the first three epidemics included the
      need for two years of exposure before PMSA acquisition and limitation of
      transmissibility of PMSA to age 13 to 26. With these conditions successive
      cohorts of susceptible Faroese were defined to account for the second and third
      epidemics, and they also predicted the occurrence of the fourth epidemic. Further
      consideration of these models suggests transmissibility is even more limited,
      perhaps to age 20 to 26 or so.

PMID- 7639060
TI  - Leber's hereditary optic neuropathy associated with a disorder indistinguishable
      from multiple sclerosis in a male harbouring the mitochondrial DNA 11778
      mutation.
AB  - This report describes a multiple sclerosis (MS)-like disorder in a male patient
      with Leber's hereditary optic neuropathy (LHON) harbouring the mitochondrial DNA
      11778 base pair mutation. Given the population frequencies of MS and LHON,
      coincidental occurrence is unlikely. Hypothetically the mitochondrial mutation
      underlying LHON may contribute to presumably immunologically mediated involvement
      of other myelinated axons in the central nervous system in susceptible
      individuals, producing a disorder indistinguishable from MS. We recommend that
      investigation for oligoclonal bands in CSF, evoked potentials and MR brain scan
      in these patients be supplemented with mitochondrial DNA analysis.

PMID- 7639061
TI  - Hyperbaric oxygen for multiple sclerosis. Review of controlled trials.
AB  - This review assesses the evidence of the efficacy of hyperbaric oxygen in
      multiple sclerosis. Material & methods - We used a list of predefined criteria
      for good methodology and interpreted the results of 14 identified controlled
      trials with emphasis on the quality. Results - At least eight trials can be
      considered to have a reasonable to high quality. In one of these 8 trials the
      results were in favour of hyperbaric oxygen treatment; the others found no clear
      positive effects. The patients had chronic progressive or chronic stable multiple
      sclerosis. In most trials, hyperbaric oxygen was supplied at pressures of 1.75-2
      ATA, during 20 sessions of 90 min in 4 weeks. The principle endpoint was the
      (Expanded) Disability Status Score [(E)DSS] and the Functional Status Score as
      described by Kurtzke. Also specific outcomes such as evoked potentials were
      frequently used, but no consistent positive effects were demonstrated. Side
      effects were generally minor, ear and visual problems predominated. Conclusions -
      The majority of controlled trials could not show positive effects. Further
      evidence might consist of trials in patients with disease of recent onset or with
      other dosing regimens but the case for such further trials is not strong.
      Considering the state of affairs we cannot recommend the use of hyperbaric oxygen
      in the treatment of multiple sclerosis.

PMID- 7639062
TI  - Multiple choice vocabulary test MWT as a valid and short test to estimate
      premorbid intelligence.
AB  - The discrepancy between current and premorbid ability is a relevant indicator of
      acquired mental impairment, which itself is closely related to general cerebral
      dysfunction. The use of tests sensitive to cerebral dysfunction, raises
      relatively few problems compared with tests being resistant that are used to
      estimate premorbid mental ability. For premorbid ability, verbal tests assessing
      knowledge, especially vocabulary, have been shown to be valid. A test, possibly
      more insensitive to brain dysfunction than the ones usually administered, is the
      multiple choice vocabulary test (MWT = Mehrfachwahl-Wortschatz-Test). At present
      only German versions are available. They are presented in some detail because of
      their advantages. Construction of the MWT is simple, and it can be easily
      administered in about five minutes. The results correlate fairly well with global
      IQ in healthy adults (median of r = 0.72 in 22 samples) and are more insensitive
      to current disturbances than such tests as the WAIS vocabulary test. The
      limitations of premorbid tests with respect to diagnostic validity are discussed.
      It is concluded, that studies which do not control premorbid intelligence have to
      be considered as a "malpractice" and should not be accepted by scientists.

PMID- 7639063
TI  - Course of attention and memory after common whiplash: a two-years prospective
      study with age, education and gender pair-matched patients.
AB  - Attentional functioning and memory of common whiplash patients were evaluated
      during the first two years after experiencing injury. The study was based on a
      non-selected sample of 117 whiplash patients referred from primary care and
      recruited according to a strict injury definition. All patients had a similar
      socioeconomic background, all being injured in automobile accidents and fully
      covered by insurance plans. Two years following initial trauma, 21 patients
      remained symptomatic. For each of these 21 patients, a counterpart matched by
      age, educational attainment and gender was selected from the group of patients
      who had fully recovered during the follow-up period. Symptomatic patients and
      matched controls were compared with regard to baseline, six-months and two-years
      findings. Examinations included testing of different aspects of attention (i.e.
      Digit Span, Corsi Block-Tapping Test, Trail Making Test, Number Connection Test,
      Paced Auditory Serial Addition Task) and memory functioning (California Verbal
      Learning Test). Cognitive functioning was assessed in conjunction with self
      ratings of cognitive abilities (Cognitive Failures Questionnaire), well-being
      (Well-being Scale), headache and neckpain intensity, utilized medication and
      subjective complaints. Results show no impairment of memory in symptomatic
      patients. In attentional functioning, different levels of improvement were found
      for symptomatic patients and matched counterparts, with the former showing
      difficulty at follow-up with tasks of divided attention. Utilized medication and
      pain intensity could not explain this difference in recovery of attentional
      functioning between the groups. These findings suggest problems in selective
      aspects of attentional functioning after common whiplash, which under real life
      circumstances may explain these patients' cognitive complaints and cause
      adaptational problems in daily life.

PMID- 7639064
TI  - Lyme encephalopathy: long-term neuropsychological deficits years after acute
      neuroborreliosis.
AB  - We studied long-term cognitive deficits in 20 patients with previously diagnosed
      Lyme borreliosis several years (average 51.6 months) after their acute phase of
      illness. Compared with an age- and education matched control group Lyme patients
      revealed deficits of verbal memory, mental flexibility, verbal associative
      functions and articulation, but performed adequately on tests of intellectual and
      problem solving skills, sustained attention, visuoconstructive abilities and
      mental speed. The late cognitive outcome was unrelated to disease variables from
      the acute stage of illness, but also to the interval elapsed since infection with
      B. burgdorferi. These and similar observations (Krupp et al. 1991) suggest that
      the so-called Lyme encephalopathy may be associated with a long-lasting
      neuropsychological deficit predominantly affecting mnestic functions.

PMID- 7639065
TI  - Cognitive event-related potential in hepatic encephalopathy.
AB  - A study of auditory P300 was performed on 24 patients with cirrhosis of the
      liver: 13 patients with hepatic encephalopathy (HE grade 1-2) and 11 patients
      without clinical encephalopathy (HE grade 0). The patients were also assessed
      using spontaneous EEG and neuropsychological methods: Mini Mental State, Digit
      Span and Number Connection Test. The P3 latency was found to be significantly
      increased in all patients (100%) with HE grade 1-2 and in 6 patients (54.5%) with
      HE grade 0. The clinical value of using the P300 latency in the hepatic
      encephalopathy is subsequently discussed.

PMID- 7639066
TI  - Auditory event-related magnetic fields in a tone-duration discrimination task.
      Source localization for the mismatch field and for a new component M2".
AB  - Auditory event related magnetic fields were measured using an odd-ball paradigm
      in which the rare event was a tone of short duration, D2, and the frequent one a
      tone of longer duration, D1. The subjects were required to attend to and count
      the number of rare stimuli. In the average across target stimuli a mismatch field
      (MMF) occurs and the dependence of the MMF, especially its latency, on the tone
      duration D2 is examined in detail. The location of an equivalent current dipole
      for the MMF-source is found and turns out to be at variance with earlier results.
      In addition to the MMF we propose a new component, here called M2", which in time
      overlaps the magnetic equivalent of the P200 signal and which has a source
      location (equivalent current dipole) lying rather close to the MMF-source. The
      two sources are, however, active at latencies differing by a time equal to D2. We
      speculate that M2" indicates the onset of the process: "evaluation of tone
      duration" while the MMF indicates the end of this process.

PMID- 7639067
TI  - Sympathetic skin responses (SSRs) in monofocal brain lesions: topographical
      aspects of central sympathetic pathways.
AB  - Lesions of the central sympathetic pathways are likely to be of clinical
      relevance. In patients with acute stroke, in particular, they may be responsible
      for the partially deleterious cardiac arrhythmia. There is little knowledge of
      the central organization of sympathetic pathways above the brainstem level for
      both cardio-efferent and sudomotor fibers. We studied the sympathetic skin
      response (SSR) in 29 patients with brainstem stroke or infarction in the
      territory of the middle cerebral artery (MCA) in order to evaluate the pathways
      mediating emotional sweating. In 24 patients (82.8%) the SSR was pathological.
      These abnormalities were bilateral with no clear asymmetry in 10 patients
      (34.5%), bilateral with marked contralateral pathology in 8 patients (27.6%),
      purely contralateral in 5 patients (17.2%) and purely ipsilateral in one patient
      (3.5%). Bilateral abnormalities were more frequent and more marked in brainstem
      than in MCA stroke. This is probably indicative of a more generalized sympathetic
      dysfunction. In contrast, contralateral abnormalities were more pronounced in MCA
      than in brainstem infarcts. Our results show that sympathetic skin responses are
      suppressed in the majority of stroke patients. Asymmetric responses may indicate
      that sudomotor fibers mediating emotional sweating have their origin or receive
      input from the contralateral MCA territory.

PMID- 7639068
TI  - Asterixis associated with anatomic cerebral lesions: a study of 45 cases.
AB  - INTRODUCTION: Asterixis is an uncommon sign in structural central nervous system
      disorders. When asterixis is present, one cannot rule out the possibility of a
      focal lesion, but it is almost always due to a metabolic encephalopathy. PATIENTS
      AND METHODS: In the last five years all patients with uni- or bilateral
      neurologic asterixis attended in our hospital have been studied. Cerebral
      computed tomogram or magnetic resonance imaging was performed in all patients
      with uni or bilateral asterixis. RESULTS: We describe 45 patients with different
      forms of structural cerebral pathology who presented unilateral (37 patients) or
      bilateral (8 patients) asterixis not associated to either toxic or metabolic
      disorder. Central nervous system ischemic or hemorrhagic disorders were found to
      be the most frequent causes of asterixis (95.5%) and the thalamus the most
      frequent localization for unilateral asterixis to result (54%). CONCLUSIONS:
      Bilateral asterixis is not always associated with toxic or metabolic disorders
      and it may be a sign of some structural neurologic alterations. A good
      correlation was found between the presence of unilateral asterixis and structural
      intracranial disease.

PMID- 7639069
TI  - Sleep-apnoea and autonomic dysfunction: a cardiopressor and pupillometric study.
AB  - Isolated alterations in the autonomic nervous system (ANS) have been described in
      obstructive sleep-apnea syndrome (OSAS), but the exact nature and degree of ANS
      involvement in OSAS is as yet uncharted. In the present study we evaluated some
      autonomic nervous functions in 13 OSAS patients using cardiopressor and
      pupillometric tests. Almost all showed only slight alterations of ANS function,
      generally in the form of a hypofunction of both sympathetic and parasympathetic
      branches. Pupillometry was more sensitive than cardiovascular indexes in
      detecting neurovegetative involvement which correlated with some respiratory
      indices. The data suggest that autonomic involvement in OSAS is ascribable to
      metabolic changes (hypoxia, hypercapnia) rather than to primary "neurogenic"
      alterations.

PMID- 7639070
TI  - Thermal threshold determination in alcoholic polyneuropathy: an improvement of
      diagnosis.
AB  - Reports on the incidence of alcoholic polyneuropathies are variable depending on
      diagnostic tools. In this study, 50 chronic alcoholics with positive MALT (Munich
      Alcoholism Test) and greater than seven years history of excessive alcohol abuse
      were examined neurologically. Tibial and peroneal motor and sural nerve
      conduction velocities (NCV) were studied. Warm and cold perception was evaluated
      in the area behind the internal malleolus using a Somedic-Thermotest. Thresholds
      were determined by the method of limits. The effect of a slow, medium and fast
      temperature change rate on thermal perception was tested. Thirty-eight patients
      (76%) showed signs of neuropathy. Thermal perception was more often abnormal
      (62%) than NCV (42%) and clinical examination (56%). A medium temperature change
      rate of 2.0-2.5 degrees C/s was the most sensitive index of small fiber
      neuropathy. Thermal threshold measurement proved to be a reliable, sensitive and
      easy to perform method that should become standard in the examination of
      polyneuropathies.

PMID- 7639071
TI  - Alpha-1-antitrypsin phenotypes and associated disease patterns in neurological
      patients.
AB  - INTRODUCTION: Alpha-1-antitrypsin (AAT) deficiency is usually associated with
      lung or liver disease. It is often detected as a qualitative reduction of the
      alpha-1 band on the serum protein electrophoretic pattern. MATERIAL AND METHODS:
      We examined the protein electrophoretic pattern in sera of 22980 unselected
      consecutive patients with neurological disorders and noted a reduced alpha-1 band
      in 88. Their phenotypes were compared with the clinical disease. RESULTS: 75
      patients had a deficient or non-M and 13 the usual MM phenotype. Contrary to in
      the general population, PiMZ was four times more common than PiMS. Vascular
      disease was more common in patients with PiMZ while multiple sclerosis
      significantly more frequent in patients with PiMS than with other phenotypes,
      including PiMM. CONCLUSIONS: Other genetic abnormalities have previously been
      found in AAT associated with multiple sclerosis, but not PiMS. Since PIMS leads
      to modest reduction of AAT activity, the association may be through other
      mechanisms than reduced protease activity.

PMID- 7639072
TI  - Clinical characteristics of rapidly progressive leuko-araiosis.
AB  - INTRODUCTION: 38 patients found to have either pure leuko-araiosis (LA) or LA
      combined with infarction(s) on computer tomography (CT) in 1989 were re-examined
      in 1992 in order to evaluate the progression of LA. The follow-up period averaged
      3.2 years. MATERIAL AND METHODS: The clinical and radiological data on patients
      in 1989 were collected from hospital records and re-evaluated. The patients were
      re-examined clinically (including 24 hour ambulatory blood pressure measurement),
      and neuroradiologically (CT) in 1992 for this study. RESULTS: 11 (29%) patients
      were found to have significant (rapid) progression of the extent of LA on CT
      during the follow-up. At baseline, there was no significant difference in the
      mean number of brain infarctions between the groups with progressing (prLA) and
      non-progressing LA (nprLA) or between the number of cortical and central
      infarctions within these groups. At follow-up, the total number of infarctions
      had increased significantly in both groups, but it was mostly because of the
      increase in cortical infarctions in the prLA group (p = 0.043) and, conversely,
      the central ones in the nprLA group (p = 0.011). prLA was found to be related to
      heart failure (82% vs 37%, p = 0.029) and atrial fibrillation (55% vs 19%, p =
      0.047), whereas nprLA was strongly associated with a sudden onset of symptoms
      (78% vs prLA 18%, p = 0.001) like a true brain infarction. Other clinical
      factors, including mean blood pressure and heart rate, did not clearly
      differentiate between the groups. CONCLUSION: The results suggest that there are
      different subgroups of patients with LA associated with various vascular factors.
      The occurrence of LA is not related to the distribution of infarctions. The
      progression of LA is not related to the number of brain infarctions or to the
      simultaneous increase of infarctions on CT.

PMID- 7639073
TI  - High acceptability and low morbidity of diagnostic lumbar puncture in elderly
      subjects of mixed cognitive status.
AB  - A total of 273 participants (186 with clinical dementia; 87 "normal" controls;
      mean age 72 years) in a prospective, longitudinal, dementia research study,
      underwent lumbar puncture (LP), where possible, on an annual basis. Reporting of
      symptoms after all LP's (n = 541) was 21.6%, the predominant complaints being
      mild localised back-pain (12.8%) and headache (10.7%). All symptoms were self
      limiting. Analysis of headaches after all first LP's (n = 273) revealed an
      incidence of 14.2% with marked differences between subjects under 60 years of age
      (33%) and those over 60 years (10.1%), between subjects with "minimal" cerebral
      atrophy (19.5%) and those with "significant" atrophy (5.6%) and, to a lesser
      extent, between subjects with no or mild cognitive impairment (20.6%) and those
      with significant impairment (9.5%). Age under 60 years and lack of significant
      cerebral atrophy were shown to be independent predictors of headache.
      Acceptability of LP was high as demonstrated by agreement to a second procedure
      by 92.2% of eligible subjects. Our results show that LP can be successfully
      incorporated into research with the elderly.

PMID- 7639074
TI  - Increased levels of plasma von Willebrand factor in migraine crisis.
AB  - INTRODUCTION: To evaluate the participation of the vessel wall in the
      pathogenesis of migraine attack, we measured the plasma levels of von Willebrand
      factor (vWF), a protein secreted from the endothelial cells. MATERIAL & METHODS:
      17 patients suffering from migraine without aura and 25 healthy volunteers were
      studied. von Willebrand factor and platelet aggregation tests were studied by
      conventional methods. RESULTS: The levels of vWF:antigen increased from 72.4 +/-
      29 U/dl in the intercrisis to 130.2 +/- 75 U/dl during the attack (p < 0.01). We
      did not detect difference in the platelet aggregability in both phases. Plasma
      vWF activity measured as ristocetin cofactor (vWF:RCo) was similar in intercrisis
      and crisis (100.6 +/- 31 U/dl vs 94.5 +/- 44 U/dl). CONCLUSIONS: There is a
      plasma release of vWF molecules during the migraine crisis. This feature is not
      platelet dependent and is probably a consequence of endothelial stress.

PMID- 7639075
TI  - Painful unilateral epileptic seizure.
AB  - Two rare cases with focal, paroxysmal pain as the initial manifestation of
      partial epilepsy have been reported. The pain attacks subsided after treatment
      with anti-epileptic drugs.

PMID- 7639076
TI  - Exacerbations of myasthenia gravis after removal of thymoma.

PMID- 7639077
TI  - High cervical myelopathy and tactile object recognition disturbance.

PMID- 7639078
TI  - [Effects of dopexamine on the electrophysiologic changes during myocardial
      ischemia and comparison with fenoldopam and procaterol].
AB  - The effects of dopexamine (DPX), a new dopamine receptor agonist, on
      transmembrane potential and effective refractory period (ERP) of isolated guinea
      pig ventricular muscle superfused either with hypoxia or mimic ischemia
      perfusates were investigated by using intracellular microelectrode technique and
      compared with fenoldopam (FODA) and procaterol. DPX (3 x 10(-6) mol.L-1) was
      found to significantly reduce both the extent of decrease of resting potential,
      action potential amplitude and maximal upstroke velocity and the degree of
      shortening of action potential duration caused by hypoxia or ischemia. These
      effects of DPX were significantly greater than those of FODA and procaterol
      albeit the latter showed effects similar to DPX. DPX could not only lengthen the
      abbreviated ERP resulting from hypoxia, but also shorten the prolonged ERP caused
      by ischemia. This action of DPX was more evident than that of FODA and
      procaterol. The results reveal the potential advantages of DPX over other
      dopaminergic agonists in the antiarrhythmic activity during myocardial ischemia.

PMID- 7639081
TI  - [Protective effects of salvianolic acid A against impairment of memory induced by
      cerebral ischemia-reperfusion in mice].
AB  - In the present experiments, an impairment of memory model was made by cerebral
      ischemia-reperefusion in mice. Sal A at the dosage of 3 and 10 mg.kg-1 i.v. was
      shown to improve the impairment of memory function induced by cerebral ischemia
      reperefusion in step down and step through tests. In these tests, the number of
      errors of Sal A treated group was less and the latency was longer than that of
      control group. Meanwhile, Sal A 3 and 10 mg.kg-1 i.v. was found to reduce the MDA
      contents in the cortex, hippocampus and striatum of cerebral ischemia-reperfused
      rats in vivo. Sal A 10-100 nmol.L-1 was shown to inhibit the brain lipid
      peroxidation and scavenge the free hydroxyl radical in vitro. These results
      indicate that the antagonistic effects of Sal A on impairment of learning and
      memory caused by cerebral ischemia-reperefusion may be related with its anti
      oxidant activity.

PMID- 7639080
TI  - [The antihepatoma effect of lyophilized aclacinomycin A polyisobutylcyanoacrylate
      nanoparticles in vitro and in vivo].
AB  - This paper reports the results of experiments on the antihepatoma effects of live
      targeted drug delivery system--lyophilized aclacinomycin A
      polyisobutylcyanoacrylate nanoparticle (ACM-IBC-NP) in vitro and in vivo. The
      median inhibition concentration were found to be 0.28 micrograms.ml-1 and 0.34
      micrograms.ml-1 of lyophilized ACM-IBC-NP and ACM respectively in vitro. The
      inhibition ratio of colony formation were found to be 99% and 88% of lyophilized
      ACM-IBC-NP and ACM respectively in vitro. The antihepatoma activity was shown to
      be significantly concentration dependent. The results showed that lyophilized ACM
      IBC-NP and ACM possess strong cytotoxicity on human hepatoma cell 7703, and the
      cytotoxicity was not significantly different between lyophilized ACM-IBC-NP and
      ACM in vitro. The model of orthotopic transplantation of human hepatoma in nude
      mice were used for evaluation of the activity of lyophilized ACM-IBC-NP against
      hepatoma. The tumor inhibition rate were found to be 86.84% for lyophilized ACM
      IBC-NP and 46.69% for ACM. The cell proliferative activity of hepatoma were found
      to be 20.83% by lyophilized ACM-IBC-NP and 72.50% by ACM. All the results
      indicate that lyophilized ACM-IBC-NP and ACM have clinical application potential
      and the antihepatoma activity of lyophilized ACM-IBC-NP was obviously higher than
      that of ACM.

PMID- 7639079
TI  - [NONMEM approach for estimating population pharmacokinetic parameters of
      phenytoin in Chinese epileptics].
AB  - Routine clinical pharmacokinetic data collected from epileptic out-patients who
      received phenytoin (PHT) were analysed to estimate population pharmacokinetic
      parameters. There were 258 steady-state serum phenytoin concentrations and
      associated dosage (mg.d-1) from 161 out-patients. The data were analysed using
      NONMEM program. The influence of body weight, drug combinations and sex on the
      maximum elimination rate (Vm) and age on the Michaelis-Menten constant (Km) were
      investigated. The Vm and Km of phenytoin in a 60 kg adult out-patient, without
      combination with other drugs (phenobarbital, clonazepam or diazepam) were
      estimated to be 439 mg.d-1 and 6.21 micrograms.ml-1, respectively. The best
      function adjusts Vm to the 0.57 power in proportion to body weight. The Km for
      patients less than 15 years old was 7% less than that for adults. The Vm of
      patients treated with phenytoin combined with phenobarbital, clonazepam or
      diazepam will increase 8.4 mg.d-1.

PMID- 7639082
TI  - [Comparison of concentration of piroxicam in blood and local site after two
      routes of administration].
AB  - The systematic and local concentrations of piroxicam after oral and transdermal
      administration were determined and compared. Mice were randomly grouped, and oral
      suspensions (0.72 mg.ml-1) or transdermal gels 1 mg.ml-1 were given. Systematic
      concentration (Cs) and local concentration (C1) of the drug in each mouse were
      determined by HPLC method. After transdermal administration of 0.25 mg of
      piroxicam gels Cmax(s) = 8.06 micrograms.ml-1 and AUC(s)0-24(s) = 58.36
      micrograms.h.ml-1 were obtained, whereas after oral administration of 0.026 mg.10
      g-1 body weight of piroxicam suspensions Cmax(s) was 36.82 micrograms.ml-1 and
      AUC(s)0-24 was 155.59 micrograms.h.ml-1. The C1/Cs ratio (0.01) through oral
      route was far lower than the C1/Cs ratio (0.13) through transdermal route. The
      area under local concentration-time curve (15.85 micrograms.h.ml-1) calculated
      from transdermal administration was much higher than that from oral
      administration (1.93 micrograms.h.ml-1). So, it seems to be unreasonable that
      only serum concentration is taken as a criterion for bioavailability test of
      piroxicam for local dosage forms, the local drug concentration should also be
      investigated and evaluated.

PMID- 7639084
TI  - Cerebrospinal fluid levels of phenylacetic acid in mental illness: behavioral
      associations and response to neuroleptic treatment.
AB  - Cerebrospinal fluid levels of phenylacetic acid (CSF PAA) were obtained from
      normal controls and from drug-free psychiatric inpatients (schizophrenia, major
      depression, mania, and schizoaffective disorder). Post-treatment CSF PAA levels
      were obtained from 16 patients after 4 weeks of neuroleptic treatment.
      Phenylacetic acid levels were higher in women and were significantly correlated
      with age. There were no differences in CSF PAA levels between the various
      diagnostic groups and no difference between the paranoid and the nonparanoid
      subtypes of schizophrenia. CSF PAA was significantly correlated with several
      measures of psychopathology, especially the Brief Psychiatric Rating Scale
      hostility/suspiciousness factor. Neuroleptic treatment did not result in
      significant PAA changes. These findings are discussed in light of the amphetamine
      like role ascribed to phenylethylamine, the precursor of PAA.

PMID- 7639083
TI  - Slow-wave sleep deficits and outcome in schizophrenia and schizoaffective
      disorder.
AB  - Schizophrenia is associated with altered sleep architecture, particularly in
      regard to delta sleep. We examined the relation between the baseline
      polysomnographic measures in schizophrenic and schizoaffective patients and
      psychosocial outcome as measured by the Strauss & Carpenter scale at 1 (n = 20)
      and 2 (n = 7) years. The percentages of delta sleep at baseline were
      significantly correlated with total outcome scores at 1 and at 2 years. These
      preliminary findings suggest that delta sleep deficits may be associated with
      relatively poor outcome in this disorder.

PMID- 7639085
TI  - Neuropsychological changes during steady-state drug use, withdrawal and
      abstinence in primary benzodiazepine-dependent patients.
AB  - Impairment on neuropsychological tests during steady-state drug use and
      withdrawal, and after discontinuation of benzodiazepines, was studied in primary
      benzodiazepine-dependent patients. One group of patients was tested before and
      the other group after the initiation of a gradual tapering-off of the drug, and
      both groups were tested approximately 1 year later. At the initial assessment,
      both groups of patients showed impairment on most of the tests of general
      intelligence and on several of the tests in the Halstead-Reitan battery, as well
      as on a test of nonverbal memory, in comparison with healthy controls. At follow
      up the patient groups had reached the level of the control group. This study
      confirmed earlier observations of neuropsychological deficits in long-term
      benzodiazepine-using patients and demonstrated that these changes are at least
      partly reversible by discontinuing drug intake.

PMID- 7639086
TI  - Educational level and hospital use in mental disorders. A population-based study.
AB  - This population-based study presents socioeconomic differences in psychiatric
      inpatient care by diagnosis. Inpatient care among the Finnish population aged 25
      64 years was studied using data from the Finnish National Hospital Discharge
      Register. All major mental disorders in the ICD-9 were included in the study. The
      socioeconomic status of individual patients was defined by years of education in
      the population census. Discharge rates, first-time admission rates and
      hospitalization risk were usually 2- to 4-fold higher in the low educational
      group compared with the highly educated population. The socioeconomic gradient
      was steepest for schizophrenia. No gradient was observed for major affective
      disorders. However, bipolar disorder was most common in the highest educational
      category. For most conditions, the socioeconomic gradient among women was lower
      than among men. In Finland hospitalization was more common among low than high
      socioeconomic groups for most mental disorders and most indicators of inpatient
      care. Most of these differences are fairly consistent with previous data on
      socioeconomic gradients in the prevalence of mental disorders.

PMID- 7639088
TI  - Coping with life span crises in a group at risk of mental and behavioral
      disorders: from the Lundby study.
AB  - The subjects belong to a prospective, longitudinal population study on mental
      health, the Lundby study, performed in 1947, 1957 and 1972. In 1988-1989, 148
      individuals, then 42-56 years of age, raised in families with at least 3 risk
      factors for mental or behavioral disorders, were interviewed about their life
      span coping style. Twenty-two coping mechanisms were rated; optimism,
      substitution, wishful thinking, problem-solving, planning, self-reliance, humor,
      acceptance, resignation, social support, comparison with others, religion,
      catharsis, self-criticism, value reinforcement, alcohol and drug consumption,
      professional help, endurance, information-seeking, isolating activity, magic and
      minimizing. Together they contributed statistically significantly to mental
      health (explained variance 24%) and quality of life (explained variance 28%).
      Problem-solving, social support and optimism were frequently used and were
      statistically associated with positive mental health and lower frequencies of
      some mental disorders. Sense of coherence, a personal disposition factor, was
      also statistically associated (explained variance 22%) with the combined coping
      mechanisms.

PMID- 7639087
TI  - Classification of patients with affective disorders using platelet monoamine
      oxidase activity, serum melatonin and post-dexamethasone cortisol.
AB  - Platelet monoamine oxidase activity (MAO), melatonin and cortisol post
      dexamethasone suppression test (DST) were examined in 28 patients with major
      affective disorder and in 20 controls. MAO activity was lower and cortisol post
      dexamethasone was higher in depressed patients. Platelet MAO activity and
      cortisol in depressed and controls yielded high sensitivity (90%) and specificity
      (89%). The patients were re-examined after 10 years and categorized into
      affective psychosis or neurotic depression (ICD-9). Multidimensional analysis
      identified one subgroup coinciding in 92% with affective psychosis and another
      subgroup coinciding in 87% with neurotic depression. Combination of MAO,
      melatonin and post-DST cortisol may be useful in the diagnosis of subgroups of
      depressed patients and in choice of therapy.

PMID- 7639089
TI  - Compliance with treatment in schizophrenia: a drug intervention program in a
      developing country.
AB  - The compliance with drug regimens and follow-up visits of 225 known cases of
      relapsed schizophrenia was assessed. About 27% of the patients met the criteria
      for good compliance. The compliance was found to be significantly related to the
      patients' view of usefulness of the medication, treatment duration of less than 5
      years, dosage schedule of once or twice per day and the supervision of medication
      at home. Patients with poor compliance who were prescribed drug dosage of not
      more than twice per day throughout follow-up and underwent counseling to enhance
      treatment compliance had a significantly lower relapse rate than the controlled
      group at the end of 1 year of follow-up. The importance of family support and
      understanding patients' cultural background in ensuring good compliance was
      highlighted.

PMID- 7639090
TI  - Survival analysis of suicide risk after attempted suicide.
AB  - Survival analysis of suicide risk by sex and age after attempted suicide was
      studied in a cohort of 1573 suicide attempters referred to the psychiatric
      emergency room at the Karolinska Hospital from 1981 to 1988. The time course of
      suicide risk and the overall prognosis after attempted suicide and, in
      particular, the possible usefulness of sex and age as risk factors for the
      prediction of suicide risk after attempted suicide was analyzed. Nearly two
      thirds of the sample were women and most of the suicide attempters were young (in
      their twenties and thirties), and the median age was 35 years. The overall
      mortality after a 5-year mean observation period after attempted suicide was 11%,
      and the suicide mortality was 6%. The suicide risk after attempted suicide among
      men (8.3%) was nearly twice the female suicide risk (4.3%). Age as a possible
      suicide risk factor was analyzed for each sex separately by median split
      subgrouping. It was concluded that both older and younger male suicide attempters
      are at high risk of suicide (7% and 10% respectively), and older women are at
      higher risk than younger (6% vs 2%). The suicide risk is particularly high during
      the first year after the suicide attempt. The high suicide risk group of young
      adult male suicide attempters is one of the main feasible targets of psychiatric
      intervention research programs on suicidal behavior. Suicide among young men is a
      major cause of years of life lost.

PMID- 7639091
TI  - Reliability of the ICD-10 diagnostic criteria for research in mental disorders in
      the Republic of Korea.
AB  - The interrater reliability, confidence and ease of use of ICD-10 diagnostic
      criteria for research were assessed in the Republic of Korea as part of the field
      trials of World Health Organization collaborative study. A total of 279 patients
      were diagnosed according to the ICD-10 diagnostic criteria for research.
      Interrater reliability, calculated by kappa statistics, was found to be between
      0.74 and 0.91 on 2-character categories and between 0.64 and 0.90 on 3-character
      categories except schizotypal disorder (F21). On the 4-character categories, the
      agreement in the affective states between raters was lower. The reasons are
      discussed based on cultural differences.

PMID- 7639092
TI  - Citalopram, a selective serotonin reuptake inhibitor, in the treatment of
      aggression in schizophrenia.
AB  - The aim of this double-blind cross-over study was to investigate whether
      treatment with the selective serotonin reuptake inhibitor, citalopram reduces
      aggressiveness in chronically violent schizophrenic inpatients. Initially 19
      patients were enrolled into this double-blind cross-over study in which the
      patients were treated for 24 weeks with placebo and 24 weeks with citalopram (20
      60 mg/day) as a supplement to their previous neuroleptic medication. Fourteen
      patients completed the entire study, but sufficient data on 15 patients could be
      used in the end-point analysis of efficacy. Psychiatric assessments (Brief
      Psychiatric Rating Scale, Clinical Global Impression Scale for Severity of
      Illness, Social Dysfunction and Aggression Scale and the Global Aggression Scale)
      and side effects (UKU Side Effect Scale) were recorded at baseline and 4 times
      during both periods. Aggressive incidents (Staff Observation Aggression Scale)
      were recorded throughout the study. During citalopram treatment, the frequency of
      aggressive incidents was significantly lower and the mental state did not
      deteriorate. Patients either experienced no side effects or else side effects
      were equally mild during both periods.

PMID- 7639093
TI  - Light treatment in seasonal and nonseasonal depression.
AB  - Ninety patients with major depressive disorder were classified according to
      seasonal (n = 68, 50 women) or nonseasonal (n = 22, 17 women) pattern according
      to DSM-III-R. They were also clinically evaluated and rated before and after
      morning (0600-0800) or evening (1800-2000) light treatment for 10 days in a room
      with a luminance of 350 cd/m2 (approximately 1500 lx) at eye level. Mood ratings
      were performed using both the Comprehensive Psychopathological Rating Scale and
      the Hamilton Depression Rating Scale. Depressed patients with seasonal pattern
      improved significantly more than those with a nonseasonal pattern suggesting a
      specific nonplacebo effect of light treatment in depressed patients with seasonal
      pattern. There were no significant differences in outcome when light treatment
      was given in the morning or in the evening, and not between patients with and
      without atypical symptoms such as carbohydrate craving or increased appetite.

PMID- 7639094
TI  - Constancy and normalization in the perception of Voice Offset Time as a cue for
      preaspiration.
AB  - It is a well-established fact that the realization of individual speech segments
      is heavily dependent on context. One factor, temporal organization, has been
      shown to affect numerous speech cues, especially those which are defined in the
      temporal domain. Theories of speech perception have adopted two different views
      of the nature of these contextual effects. On the one hand it has been
      hypothesized that the listener normalizes by taking account of the context. On
      the other hand it has been hypothesized that higher-order invariants, e.g. speech
      segment ratios, are sufficient cues for the relevant temporal contrasts, thus
      obviating the need for mechanisms of normalization. The present series of
      experiments investigates the merits of these opposing theoretical positions. The
      experiments involve Voice Offset Time as a cue for preaspiration in Icelandic.
      The results indicate that durational ratios can, for the most part, function as
      higher-order invariants for the perception of preaspiration.

PMID- 7639095
TI  - Neurobehavioral, neurochemical and electrophysiological studies in 6
      hydroxydopamine lesioned and neural transplanted rats.
AB  - Unilateral injection of 6-hydroxydopamine (6-OHDA) into the caudate nucleus of
      rat caused degeneration of dopaminergic terminals, evidenced by significant (P <
      0.05) elevation of spontaneous and drug-induced motor behaviour, enhanced DA
      receptor binding and significant increase in the neuronal firing rate of caudate
      neurons, suggesting supersensitivity of dopaminergic receptors. Eight weeks
      following the transplantation of embryonic cell suspensions from caudate at the
      lesioned site, a significant restoration of the enhanced 3H spiperone binding and
      neuronal activity of caudate neurons was observed in comparison with lesioned
      rats. These results clearly demonstrate that transplanted embryonic neuronal
      tissue at the lesioned site is capable of restoring the neuronal deficits caused
      by 6-OHDA as evidenced by significant amelioration in neurochemical, behavioral
      and electrophysiological alterations.

PMID- 7639096
TI  - cis-acting signals and trans-acting proteins are involved in tau mRNA targeting
      into neurites of differentiating neuronal cells.
AB  - Tau microtubule-associated protein is a neuron specific protein found primarily
      in axons and is developmentally regulated. The function of tau is in
      stabilization of microtubules, which is important in establishing and maintaining
      neuronal morphology. Axonal localization of tau involves a multistep process
      which is studied in differentiating primary neuronal culture. The initial step
      involves sorting and subcellular localization of its encoding mRNA into the
      proximal portion of the axon. Using the transfection assay into neuronal cells,
      we have demonstrated that sequences located in the 3'-untranslated region include
      a cis-acting signal which is involved in tau mRNA targeting. In addition, using
      ultraviolet cross-linking assay, two RNA-binding proteins of 43 and 38 kDa were
      identified, that exhibit specific binding to a minimal sequence of 91 nucleotides
      located within the same functional region, which is involved in targeting. The 43
      and 38-kDa RNA-binding proteins are present in cytoplasmic extracts, prepared
      from neuronal cells, and in isolated microtubule preparations. Our results
      support a novel model in which cis-acting signals, together with RNA-binding
      proteins are involved in the targeting of tau mRNA, that may ultimately lead to
      its axonal localization.

PMID- 7639097
TI  - Early postnatal appearance of enhanced noradrenaline content in the brain of
      vasopressin-deficient Brattleboro rat; normal adrenoceptor densities and aberrant
      influences of vasopressin treatment.
AB  - The course of postnatal development of noradrenaline (NA) and its unconjugated
      free metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG), as well as the influence
      on early chronic vasopressin treatment, were investigated in various brain
      regions of the hereditary vasopressin-deficient (homozygous di/di) Brattleboro
      rat. In addition, the densities of the adrenergic receptor subtypes were measured
      in adult brain. Brain NA levels of di/di pups appeared enhanced already at 7 days
      of age when compared with data of heterozygous (+/di) controls. This was also
      seen in areas not known to receive a vasopressinergic input, e.g. the frontal
      cortex. Levels of MHPG also differed between genotypes, but changes were slight
      and either a decrease or increase, depending on age and region tested. Saturation
      analyses of alpha 1-, alpha 2-, and beta-adrenoceptor binding on crude membrane
      preparations of some brain regions revealed no differences in adulthood. Chronic
      treatment with vasopressin between 6 and 13 days of age reduced the enhanced NA
      brain levels throughout the brain of the di/di Brattleboro pups. The known
      vasopressin-mediated enhancement of NA turnover in adult brain was also
      measurable in +/di pups of this neonatal period (MHPG/NA ratios), indicating the
      early maturation of the interaction of vasopressinergic and NAergic systems.
      However, the dose-response in the di/di Brattleboro rat was biphasic with a
      decrease at a low dose of vasopressin. Since changes were found throughout the
      brain, it was concluded that vasopressin deficiency had altered the maturation of
      NA neurons of the locus coeruleus which may be due to the absence of a presumed
      inhibitory control of vasopressin on synthesis and storage mechanisms at the
      perikaryal level.

PMID- 7639098
TI  - Development of ependyma in neural transplants.
AB  - Under in situ conditions, the innermost (juxtaventricular) neuroepithelial layer
      of the embryonic brain wall develops into ependyma. No development of ependyma
      was usually observed, however, in transplanted embryonic brain wall. In our
      telencephalic transplants, however, cysts lined by epithelium resembling ependyma
      were observed, although only sporadically. We supposed that occasional foldings
      of the transplanted telencephalic wall enclosed the aforementioned cysts and so
      induced the formation of ependyma. This hypothesis was supported by the
      observation that ependyma developed frequently in a model system in which the
      telencephalic wall was folded artificially prior to transplantation.

PMID- 7639099
TI  - Innervation of the rat gastrointestinal sphincters: changes during development
      and aging.
AB  - The effect of age on the adrenergic and peptidergic innervation of the lower
      oesophageal, pyloric and ileocaecal sphincters of the rat was investigated using
      immunohistochemical techniques. The distribution of nerve fibres containing the
      neuronal protein, growth associated protein-43, was also studied to determine the
      integrity of the enteric nervous system during development and aging. The four
      age groups examined were 2-3 days, 6 weeks, 3 months and 25 months old rats.
      Using protein gene product 9.5 antibody (a non-specific general neuronal marker),
      it was revealed that the myenteric ganglia in all sphincter regions were
      compactly arranged and were smaller in size at neonatal stage getting more spaced
      out and larger in size with age. There was no obvious change in the structure of
      the neutral elements with age. In the lower oesophageal sphincter, calcitonin
      gene-related peptide- and substance P-like immunoreactive nerve fibres showed
      notable changes in density and fluorescence intensity with age, decreasing and
      increasing, respectively, with no obvious change in vasoactive intestinal
      polypeptide- and growth-associated protein-like immunoreactivity. A slight
      increase in dopamine-beta-hydroxylase-like immunoreactivity was seen in old age.
      In the pyloric sphincter, there was an increase in calcitonin gene-related
      peptide- and substance P-like immunoreactivity with a less notable increase in
      dopamine-beta-hydroxylase-like immunoreactivity. A decrease in vasoactive
      intestinal polypeptide- and growth-associated protein-43-like immunoreactivity in
      the circular muscle of the sphincter was seen in old age. In the ileocaecal
      sphincter there was a marked increase in growth associated protein-43-,
      vasoactive intestinal polypeptide-, dopamine-beta-hydroxylase and substance P
      like immunoreactivity. There was a decrease in the density of calcitonin gene
      related peptide-like immuno-reactive nerve fibres in old age. In summary, two
      main conclusions can be drawn from the results of the present study. First, there
      was an age-related differential change in the density of immunoreactive nerve
      fibres containing various neuroactive substances. This indicates a level of
      plasticity of the various enteric nerve types and may reflect the degree of
      importance of the different neurotrasmitters in the physiological activities of
      the specific sphincter.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7639100
TI  - The ability to re-express polysialylated NCAM in soleus muscle after denervation
      is reduced in aged rats compared to young adult rats.
AB  - The neural cell-adhesion molecule, NCAM, contains an unusual homopolymer of
      sialic acid units, polysialic acid. This carbohydrate seems to be involved in
      neurite outgrowth, bundling and branching, processes which are important during
      reinnervation. In aged rats, reinnervation of denervated muscle fibres is
      incomplete. In this study, age-related changes in the degree of polysialylation
      of NCAM re-expressed after denervation were examined using a monoclonal antibody
      recognizing polysialic acid and a polyclonal antibody recognizing NCAM. The
      results show that, after denervation, the degree of polysialylation on NCAM was
      clearly reduced in rat soleus muscle of aged, compared to young, adult rats. This
      age-related change in expression of polysialic acid probably influences the
      reinnervation process in aged muscle.

PMID- 7639101
TI  - Influence of spontaneous calcium intake and physical exercise on the vertebral
      and femoral bone mineral density of children and adolescents.
AB  - Peak bone mass is determined mainly by genetic-ethnic factors, but environmental
      factors such as calcium intake and physical activity during childhood and
      adolescence could play a role. We have measured the bone mineral density (BMD) of
      151 healthy children and adolescents, ages 7-15.3 years. Density was measured by
      dual X-ray absorptiometry (DXA) at two sites (lumbar verterbrae L1-L4 and the
      upper femur), and the data were analyzed in terms of the height, weight, sexual
      maturation, spontaneous calcium intake, and physical activity. Of the children,
      57-71% had calcium intakes below 1000 mg/day. BMD increased with pubertal
      maturation from 0.68 +/- 0.08 to 0.92 +/- 0.09 g/cm2 (vertebral bone density,
      VBD) and from 0.87 +/- 0.10 to 1.03 +/- 0.09 g/cm2 (femoral bone density, FBD)
      between Tanner stage 1 and 5. Multiple regression analysis showed that body
      weight and Tanner stage were main determinants of bone density when expressed as
      g/cm2. The weekly duration of sports activity also influenced both the vertebral
      (p < 0.001) and femoral (p = 0.01) sites, especially in girls and during puberty.
      Dietary calcium appeared to be another independent determinant of BMD, especially
      before puberty, at the vertebral (p = 0.02) site. Most important, dietary calcium
      was found to be the main determinant of vertebral mineral density, when expressed
      as z score, in both sexes. Moreover, 93% of the 28 children with low vertebral z
      score values (below -1) and 84% of the 31 children with low femoral z score
      values (below -1) had dietary calcium intakes below 1000 mg/day.

PMID- 7639102
TI  - Inhibition of bone resorption and stimulation of formation by mechanical loading
      of the modeling rat ulna in vivo.
AB  - During normal growth of the rat ulna, bone is resorbed from the medial periosteal
      surface. This occurs as part of the modeling process by which the bone achieves
      its adult shape. By attaching strain gauges to the ulnae of rats in vivo, we
      measured the strains imposed on that surface of the bone during normal
      locomotion. We then applied mechanical loads to the ulnae of other rats in vivo
      for 6 consecutive days, inducing strains approximately double those we had
      measured. Fluorochromes were given on the 1st and 5th days. The histology of the
      medial ulnar periosteal surface was correlated with the amount of fluorochrome
      incorporation and tartrate resistant acid phosphatase (TRAP) activity in serial
      sections. In the nonloaded ulnae, the surfaces were lined with bone resorbing
      cells. Corresponding areas of the loaded bones were lined with osteoid and
      osteoblasts. There was insignificant label incorporation in the nonloaded bones
      but almost continuous label incorporation in the corresponding regions of the
      loaded bones, which was significantly different from the nonloaded bones. TRAP
      activity of the periosteal cells in the loaded bones was significantly less than
      in the nonloaded limbs. It is widely acknowledged that loading induces bone
      formation, and this implies that it also has the ability to inhibit resorption.
      However, to date there has been little direct evidence for the inhibition of
      resorption in vivo by mechanical loading. The changes we have observed are
      similar to the sequence of cellular events that occur during the reversal phase
      of bone remodeling, in which osteoclastic resorption ceases and osteoblasts are
      recruited and begin formation. This model may help increase understanding of that
      process.

PMID- 7639103
TI  - Osteogenic growth peptide regulates proliferation and osteogenic maturation of
      human and rabbit bone marrow stromal cells.
AB  - The recently discovered osteogenic growth peptide (OGP) has been shown to
      regulate proliferation in fibroblastic and osteoblastic cell lines derived from
      rats and mice and also alkaline phosphatase activity in the latter was found to
      be affected. In vivo the OGP enhances bone formation and trabecular bone density.
      The results of the current study indicate that the OGP is also a potent regulator
      of marrow stromal cells from man and rabbit, as well as rabbit muscle
      fibroblasts. The main OGP activity in both marrow systems is a marked stimulation
      of alkaline phosphatase activity and matrix mineralization. In the rabbit-derived
      cell culture this enhancement is accompanied by a reciprocal inhibition of
      proliferation. On the other hand, the human cells show a concomitant increase of
      both parameters. The proliferative effect of the OGP is similar to that of growth
      hormone (GH) and basic fibroblast growth factor (bFGF). The combined activity of
      the OGP with GH is smaller than that of each of the polypeptides alone. The OGP
      and bFGF potentiate each other. Of the three polypeptides tested, OGP is the most
      potent enhancer of alkaline phosphatase activity and mineralization. bFGF has no
      influence on these characteristics of osteogenic maturation. The OGP maturational
      activity is unaffected by either GH or bFGF. These data suggest that the marrow
      stromal cells serve as targets for the OGP that mediate the OGP-induced increase
      in osteogenesis. The effect on the human cells implies a role for the OGP in
      clinical situations where the osteogenic potential of bone marrow is involved.

PMID- 7639104
TI  - Cyclical clodronate is effective in preventing postmenopausal bone loss: a
      comparative study with transcutaneous hormone replacement therapy.
AB  - An investigative study was carried out for 2 years involving 124 randomly
      selected early postmenopausal women with spine bone mineral density (BMD) below
      the mean value of a normal premenopausal subject. After random division into
      three groups, the first 42 patients were treated with transcutaneous 17-beta
      estradiol (50 micrograms daily), the second 42 were treated with cyclical
      intravenous clodronate (200 mg/month iv infusion), and the third group of 40
      (controls) was left untreated. After 2 years, the total drop in BMD within the
      control group was more than 7% as opposed to the values of -0.14% +/- 0.93 in the
      estradiol group and 0.67% +/- 0.84 in the clodronate group. A change in BMD of <
      1% was considered satisfactory, and this result was obtained in 32% of the
      controls, in 79% of the estradiol group where the percentage change in BMD
      moderately correlated with serum estradiol levels (r = 0.399), and in 90% of the
      clodronate-treated patients, in whom the percentage change in BMD inversely
      correlated with basal values of markers of bone turnover. Both estrogen and
      clodronate prevent postmenopausal bone loss. The response to transcutaneous
      hormone replacement therapy may be influenced by transcutaneous absorption and by
      a lower sensitivity to estrogen. Response to cyclical clodronate seems to be
      influenced by the rate of bone turnover. An interdosage interval ranging from 2-4
      weeks appears suitable for most patients.

PMID- 7639105
TI  - Inhibitors of ER Ca(2+)-ATPase activity deplete the ATP- and thrombin-sensitive
      Ca2+ pool in UMR 106-01 osteosarcoma cells.
AB  - While calcium release from intracellular stores is a signaling mechanism used
      universally by cells responding to hormones and growth factors, the
      compartmentalization and regulated release of calcium is cell type-specific. We
      employed thapsigargin and 2,5,-di-(tert-butyl)-1,4-benzohydroquinone (tBuHQ), two
      inhibitors of endoplasmic reticulum (ER) Ca(2+)-ATPase activity which block the
      transport of Ca2+ into intracellular stores, to characterize free Ca2+
      compartmentalization in UMR 106-01 osteoblastic osteosarcoma cells. Each drug
      elicited transient increases in cytosolic free Ca2+ ([Ca2+]i), followed by a
      stable plateau phase which was elevated above the control [Ca2+]i. The release of
      Ca2+ from intracellular stores was coupled to an increased plasma membrane Ca2+
      permeability which was not due to L-type Ca2+ channels. Thapsigargin and tBuHQ
      emptied the intracellular calcium pool which was released in response to either
      ATP or thrombin, identifying it as the inositol 1,4,5-trisphosphate-sensitive
      calcium store. The results of sequential and simultaneous additions of
      thapsigargin and tBuHQ indicate that both drugs depleted the same Ca2+ store and
      inhibited the same Ca(2+)-ATPase activity.

PMID- 7639106
TI  - Peak bone mass in young women.
AB  - Increasing peak bone mineral density (BMD) or content (BMC) in young women may
      help to reduce the incidence of osteoporosis. Identifying the age when peak bone
      content or density is attained is essential to develop strategies aimed at
      optimizing peak BMD and BMC. Total body bone mineral density (TBBMD) and content
      (TBBMC) were measured by a dual X-ray absorptiometer in healthy females (n = 247,
      aged 11-32 years). TBBMD and TBBMC were modeled separately as a nonlinear
      function of age. By age 22.1 +/- 2.5 years, 99% of peak BMD is attained, and by
      age 26.2 +/- 3.7 years, 99% of peak BMC is attained. Nonlinear relationships
      between weight and TBBMD or TBBMC were also modeled. In this model, the influence
      of several parameters, including age, weight, and height, on BMC and BMD were
      simultaneously assessed. A model with age and weight described the best fit for
      TBBMD, whereas age, weight, and height described the best fit for total body
      TBBMC.

PMID- 7639107
TI  - Effects of endothelin-1 on Ca2+ signaling and secretion in parathyroid cells.
AB  - It has been previously reported that parathyroid cells express endothelin (ET)
      receptors and secrete ET-1 in an extracellular Ca2+ concentration ([Ca2+]e)
      dependent manner. Here, we examined the effects of ET-1 on intracellular
      signaling and parathyroid hormone (PTH) secretion in dispersed bovine parathyroid
      (bPT) cells, which comprise several cell types including epithelial and
      endothelial cells, in two cell lines, the rat parathyroid epithelial (PT-r) and
      the bovine parathyroid endothelial (BPE-1) cells. An RNA-polymerase chain
      reaction analysis revealed that both ETA and ETB receptors are expressed in
      bovine parathyroid tissue and BPE-1 cells, and only the ETA receptor is expressed
      in PT-r cells. PT-r cells also expressed an inositol 1,4,5-trisphosphate
      (Ins[1,4,5]P3) receptor, and ionomycin induced an increase in the intracellular
      Ca2+ concentrations ([Ca2+]i) in a Ca(2+)-deficient medium, indicating the
      presence of an operative intracellular Ca2+ pool in these cells. In cells bathed
      in 1 mM [Ca2+]e, ET-1 induced a rapid and transient increase in the Ins(1,4,5)P3
      production, which was associated with a similar profile of increase in [Ca2+]i
      and with a peak response of about 800 nM. No changes in the profile of [Ca2+]i
      responses were observed in ET-1-stimulated cells in the presence of Ca2+ channel
      blockers, or in Ca(2+)-deficient medium, indicating that Ca2+ mobilization was
      not associated with Ca2+ entry. Furthermore, a sustained stimulation with ET-1
      induced a decrease in [Ca2+]i below the prestimulatory level in a large
      population of cells, and the percentage of the cell population that shows the
      sustained decrease of [Ca2+]i increased in higher ET-1 concentrations. [Ca2+]i in
      PT-r cells was also controlled by a [Ca2+]e-dependent mechanism that changed
      [Ca2+]i from 28 to 506 nM in a 0.1-3 mM concentration range with an EC50 of 1.2
      mM, which is comparable to that reported for bPT cells. In the same range of
      [Ca2+]e, PTH secretion from bPT cells was inhibited with an IC50 of 1 mM, and ET
      1 increased PTH release in a dose-dependent manner but without affecting the IC50
      for the [Ca2+]e-dependent inhibition. Thus, the parathyroid epithelial cells
      appear to respond to ET-1 in a unique way, and the ET autocrine system can be
      regarded as a possible mechanism to modulate the sensitivity of [Ca2+]e-dependent
      PTH release.

PMID- 7639108
TI  - Surface-associated proteins from Staphylococcus aureus demonstrate potent bone
      resorbing activity.
AB  - Staphylococcus aureus infections are associated with rapid bone destruction in
      conditions such as osteomyelitis, bacterial arthritis, and infected orthopedic
      implant failure. How this bacterium induces bone destruction has not been
      defined. In studies of the role of oral Gram-negative bacteria in periodontal
      pathology, we have established that cell surface-associated proteins (SAPs) are
      potent stimulators of bone resorption. The surface-associated components from S.
      aureus have now been isolated and demonstrated to be extremely potent stimulators
      of bone resorption in the murine calvarial bone resorption assay. Bone resorption
      appears to be due to proteins, is not the result of contamination with
      lipoteichoic acid or muramyl dipeptide, and is potently inhibited by indomethacin
      and can be completely blocked by high concentrations of interleukin-1 receptor
      antagonist or TN3-19.12, a neutralizing monoclonal antibody to murine TNF. The
      SAP fraction can stimulate fibroblasts or monocytes to release osteolytic
      cytokines, but only at high concentrations. Fractionation of the SAPs by high
      performance liquid chromatography demonstrated that a number of fractions were
      osteolytically active. The most active contained a heterodimeric protein of
      molecular weight 32-36 kD. The presence of this osteolytically active surface
      associated fraction may account for the bone resorption associated with local
      infection with S. aureus.

PMID- 7639109
TI  - Inhibitory effects of basic fibroblast growth factor on chondrocyte
      differentiation.
AB  - The role of basic fibroblast growth factor (bFGF) and insulin-like growth factor
      I (IGF-I) in cartilage growth was studied in primary cultures of rat rib growth
      plate chondrocytes. Growth factors effects on expression of the proto-oncogene c
      fos, DNA synthesis, differentiation, and morphological changes were analyzed by
      in situ hybridization, 3H-thymidine incorporation, and light and fluorescence
      microscopy. In serum-deprived cells, bFGF induced a transient expression of c-fos
      with a maximal effect 15-30 minutes after stimulation. After 24 h of culture it
      had a slightly lower stimulatory effect on DNA synthesis than IGF-I, but became a
      significantly more potent mitogen than IGF-I after 48 and 72 h. The stimulatory
      effect of bFGF on DNA synthesis coincided with a decrease in collagen type II and
      IGF-II expression. In contrast, IGF-I alone stimulated expression of these genes.
      In bFGF-treated cultures, cell morphology and the appearance of actin filaments
      was changed. Polygonal chondrocytes became elongated, fibroblast-like, and the
      smooth actin filaments were brush-like and disrupted. Addition of IGF-I reduced
      these changes without affecting c-fos expression induced by bFGF. Our results
      suggest that bFGF stimulates cell proliferation by preventing terminal
      differentiation of chondrocytes. This effect is mediated by induction of c-fos
      expression and a decrease in the steady-state levels of transcripts for collagen
      II and IGF-II.

PMID- 7639110
TI  - Thapsigargin stimulates intracellular calcium mobilization and inhibits
      parathyroid hormone release.
AB  - Ca2+ and other divalent cations like Sr2+, Ba2+, and Mg2+ stimulate rapid and
      sustained increases in intracellular Ca2+ ([Ca2+]i) and 1,4,5-inositol
      trisphosphate (1,4,5-InsP3) presumably by interacting with recently identified
      parathyroid cell membrane Ca2+ receptors. We used thapsigargin (THAPS), an
      inhibitor of the microsomal Ca(2+)-ATPase, to deplete InsP3-sensitive
      intracellular Ca2+ stores to determine whether sustained increases in [Ca2+]i due
      to divalent cations require intact cytosolic Ca2+ pools. In Fura 2-loaded
      parathyroid cells, THAPS produced a gradual increase in [Ca2+]i which reached a
      steady-state level by 2-3 minutes. The effect of THAPS (3 x 10(-6) M) was
      substantial with [Ca2+]i, rising from 281 +/- 27 nM at 0.5 mM Ca2+ to a peak
      value of 684 +/- 30 nM (p < 0.0001). The addition of Sr2+ to cells at 0.5 mM
      extracellular Ca2+ induced an immediate 2- to 3-fold increase in [Ca2+]i which
      stabilized at a [Ca2+]i above baseline for > or = 10 minutes. THAPS (3 x 10(-6)
      M) pretreatment for > or = 5 minutes blocked this sustained-phase increment in
      [Ca2+]i due to Sr2+. In the absence of extracellular Ca2+, there was a slight but
      nonsignificant effect of THAPS on [Ca2+]i. Incubation of cells with THAPS did not
      change the levels of 3H-inositol phosphates (InsP3, InsP2, and InsP1) or alter
      Sr(2+)-induced accumulation of InsP3, InsP2, and InsP1.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7639111
TI  - Plasma levels of parathyroid hormone-related peptide are elevated in
      hyperprolactinemia and correlated to bone density status.
AB  - Osteopenia is an important clinical manifestation of hyperprolactinemia. Bone
      loss in these patients has mainly been attributed to concomitant deficiency of
      gonadal hormones rather than to hyperprolactinemia per se. Parathyroid hormone
      related peptide (PTHrP) is expressed in human mammary tissue, and elevated
      circulating PTHrP levels as well as concomitant hypercalcemia have been described
      during lactation. We sought to determine circulating PTHrP levels in patients
      with long-standing hyperprolactinemia and whether PTHrP may exert possible
      systemic effects on bone and mineral metabolism. We studied 45 patients (30 women
      and 15 men) with persisting hyperprolactinemia 6 +/- 4 years (mean +/- SD) after
      trans-sphenoidal surgery for prolactin-producing pituitary adenomas. PTHrP levels
      in 117 healthy controls were 10.6 +/- 7.3 pmol-eq/l (mean +/- SD). In
      hyperprolactinemic patients, plasma PTHrP was elevated to 30.3 +/- 13.4 pmol-eq/l
      (p < 0.001, n = 45), and in patients with humoral hypercalcemia of malignancy
      PTHrP levels were 52.9 +/- 29.6 (p < 0.001 to controls and hyperprolactinemic
      patients). Fifty-three percent of hyperprolactinemic patients (n = 24) had
      clearly elevated PTHrP levels (> 2 SD). Retrospective immunocytochemical studies
      of the removed pituitary adenomas from 19 patients generally showed a higher
      degree of immunoreactivity for PTHrP (1-34) in all but one case when compared
      with normal pituitary tissue. Patients with elevated circulating PTHrP levels
      showed in most instances strong immunoreactivity to PTHrP in 70-100% of tumor
      cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7639113
TI  - Ethnic differences in regional bone density, hip axis length, and lifestyle
      variables among healthy black and white men.
AB  - There are few published data on bone mass, measured by dual-energy X-ray
      absorptiometry (DXA), in healthy white or black men. Similarly, a recently
      described predictor of hip fracture among white women, hip axis length (HAL), has
      not been studied in men. We recruited 160 white and 34 black men, aged 23-80
      years, and screened for diseases and drug exposures that adversely affect
      skeletal health. We measured bone mineral density (BMD) in the lumbar spine,
      femoral neck, and radial shaft by DXA; height and weight; skin color by
      reflectometry; and hip axis length both directly from DXA output and using
      automated software in a subsample. We also obtained historical data on education,
      smoking, exercise, and fractures. There were no significant black/white
      differences in mean weight, height, body mass index (BMI), or HAL. The black men
      had higher BMDs than did the white men at every site (5% for the radius, 10% for
      the lumbar spine, and 20% for the femoral neck). Skin pigmentation and BMD were
      not significantly correlated in either group (p > 0.38). Among the white men,
      smoking was associated with lower lumbar BMD, but there was no significant
      relationship between BMD and exercise frequency in either group. There was no
      significant ethnic difference in fracture experience. We conclude that: (1) the
      higher BMD in black men than in white men is not due to greater body size, (2)
      the lower hip fracture risk reported for black men than for white men is not due
      to a difference in hip axis length; (3) skin color is not related to BMD in
      either sex.

PMID- 7639112
TI  - Generation and characterization of a human osteosarcoma cell line stably
      transfected with the human estrogen receptor gene.
AB  - Although 17 beta-estradiol (E2) replacement therapy has been shown to be
      effective in treating postmenopausal osteoporosis, the underlying mechanism
      remains unclear. The presence of low levels of functional endogenous estrogen
      receptor (ER) in some osteoblastic cells has been demonstrated, and the
      suggestion that the abundance of ER may be rate-limiting in the action of E2 on
      these cells has been made. To study the mechanism of ER in regard to E2-mediated
      effects, we stably transfected a human osteosarcoma cell line, SaOS-2, with an
      expression vector, pMV-7-ER, containing the human ER gene. We characterized six
      of the stably transfected clones. One of the stable clones, SaOS-2-ER, expressed
      extra copies of ER genes integrated into the genome as detected by Southern blot
      analysis, showed a significantly increased level of ER mRNA by RT-PCR, and
      contained an increased level of ER cytosolic protein as detected by an ER
      specific EIA. The overexpressed ER was functional and sensitive to E2 in a dose
      dependent fashion after transient transfection with a vector containing an
      estrogen response element (ERE) linked to a chloramphenicol acetyltransferase
      (CAT) reporter gene. Scatchard analysis revealed a single high-affinity binding
      site with a Kd similar to values obtained for the ER in MCF-7 breast cancer
      cells. These SaOS-2-ER cells had altered osteoblast phenotypic features including
      growth inhibition, decreased basal alkaline phosphatase activity, and decreased
      IL-6 expression and secretion. In response to E2, a greater than 2-fold increase
      in TGF-beta 1 mRNA was quantitatively measured in these ER-overexpressing
      osteoblasts. These cells may provide a sensitive and unique model for
      understanding the mechanism of E2 and ER in overall bone metabolism.

PMID- 7639115
TI  - Prevalence of low femoral bone density in older U.S. women from NHANES III.
AB  - Data on the number of U.S. women with low femoral bone mineral density (BMD) are
      currently available only from indirect estimates. We used dual-energy X-ray
      absorptiometry (DXA) measurements of femoral BMD from phase 1 of the third
      National Health and Nutrition Examination Survey (NHANES III, 1988-1991) to
      estimate prevalences of low femoral BMD in women ages 50 years and older using an
      approach proposed recently by an expert panel of the World Health Organization
      (WHO). Cutpoints for low BMD were derived from BMD data of 194 non-Hispanic white
      (NHW) women aged 20-29 years from the NHANES III dataset. The prevalence of older
      U.S. women with femoral osteopenia (BMD between 1 standard deviation [SD] and 2.5
      SD below the mean of young NHW women) ranged from 34-50% in four different femur
      regions, which corresponds to approximately 12-17 million women. The prevalence
      with osteoporosis (BMD > 2.5 SD below the mean of young NHW women) ranged from 17
      20%, or approximately 6-7 million women. Prevalences were 1.3-2.4 times higher in
      NHW women than non-Hispanic black women (NHB), and 0.8-1.2 times higher in NHW
      versus Mexican American (MA) women. The estimated numbers of NHW, NHB, and MA
      women with osteopenia were 10-15 million, 800,000-1.2 million, and 300,000
      400,000, respectively; corresponding figures for osteoporosis were 5-6 million,
      200,000-300,000, and 100,000 respectively. Thus, the first data on BMD from a
      nationally representative sample of older women show a substantial number with
      low femoral BMD.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7639114
TI  - Normal human osteoblast-like cells consistently express genes for insulin-like
      growth factors I and II but transformed human osteoblast cell lines do not.
AB  - Insulin-like growth factors I (IGF-I) and II (IGF-II) are anabolic for
      osteoblastic cells. Although expression of IGF-I and IGF-II mRNA has been
      demonstrated in rodent osteoblastic cells, little is known about IGF gene
      expression in human osteoblastic cell models. In this study we characterized IGF
      I and -II mRNA expression in (1) normal human osteoblast-like (hOB) cells, (2) a
      simian virus 40 immortalized hOB (HOBIT) cell line, and (3) human osteosarcoma
      cell lines SaOS-2, TE-85, MG-63, and U-2. Since cross-hybridization of IGF cDNA
      probes with ribosomal RNA obscures detection of some of the multiple IGF
      transcripts in human cells, we replaced Northern analysis with the more specific
      ribonuclease protection assay (RPA). We also used the reverse transcriptase
      polymerase chain reaction (RT-PCR) to assess whether mRNAs were present at trace
      levels. IGF-I mRNA expression was consistently observed in normal hOB cells only
      and by both RT-PCR and RPA. Among IGF-I transcript variants, Ea IGF-I mRNA was
      more abundant than the Eb mRNA in normal hOB cells. Trace levels of IGF-I mRNA
      were variably detected in SaOS-2 and U-2 osteosarcoma cells when RT-PCR was
      performed, but we found no IGF-I mRNA in HOBIT, TE-85, or MG-63 cells. IGF-II
      mRNA was expressed in normal hOB, HOBIT, TE-85, and U-2 cells as assessed by
      either method.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7639116
TI  - Quantitative analysis of trabecular microstructure by 400 MHz nuclear magnetic
      resonance imaging.
AB  - A new approach for the quantitative analysis of trabecular microstructure, based
      on high-field proton nuclear magnetic resonance (NMR) imaging, is presented. NMR
      is ideal because it provides high contrast between the marrow proton signal and
      the bone, which appears with background intensity. Images from 1 cm3 defatted
      specimens of trabecular bone, suspended in water doped with 1 mM Gd(DTPA) to
      shorten T1 to about 300 ms, can be obtained at a resolution on the order of 30-50
      microns and slice thickness of 150 microns, in 10 minutes at 400 MHz proton
      frequency. Digital image processing algorithms were designed and evaluated for
      the measurement of bone area fraction, perimeter length, mean trabecular
      thickness, and separation. Bone area fraction derived from the NMR images was
      found to be in excellent agreement with bone volume fraction measured
      independently (slope = 0.96, r2 = 0.924, p < 0.0001). Errors in the mean
      trabecular thickness and separation were < 6%. The effects of finite imaging
      slice thickness and signal-to-noise ratio (SNR) were also evaluated. The data
      suggest a resolution of 50 x 50 x 200 microns 3 and an SNR on the order of 10 to
      provide safe margins for precise and accurate structural analysis by means of the
      algorithms presented in this paper. The method allows simultaneous measurement at
      multiple locations within the specimen volume without the need for physical
      sectioning.

PMID- 7639117
TI  - IGF-II receptor number is increased in TE-85 osteosarcoma cells by combined
      magnetic fields.
AB  - Human osteosarcoma-derived osteoblast-like cells, TE-85, were used to assess the
      effect of a low frequency alternating magnetic field in combination with a
      controlled static magnetic field (combined magnetic fields, CMF) on insulin-like
      growth factor receptor regulation. In our culture system, application of a 15.3
      Hz CMF induces a calculated maximum electrical potential in the culture media of
      10(-5) V/m. Initial characterization of TE-85 cells demonstrated that (a) TE-85
      cells contain both type I insulin-like growth factor (IGF-I) and IGF-II receptors
      and (b) dose dependence for IGF-stimulated cell proliferation were comparable to
      the affinities of the IGF's binding to membrane binding sites (i.e., receptors
      had dissociation constants in the low nanomolar concentration range). The studies
      with CMF exposure revealed that CMF treatment for 30 minutes increased the number
      of IGF-II receptors in a frequency-dependent manner without affecting the number
      of IGF-I receptors. The CMF-dependent increase in IGF-II receptor number was
      associated with a significant increase in the IGF-II dissociation constant. These
      results indicate that a membrane receptor levels can be altered by short-term
      exposure to low-energy, low-frequency electromagnetic fields and suggest a
      potential biochemical mechanism for electromagnetic effects on bone formation and
      remodeling.

PMID- 7639118
TI  - Physical exercise during remobilization restores a normal bone trabecular network
      after tail suspension-induced osteopenia in young rats.
AB  - To determine how bone recovers from immobilization-induced bone loss and to
      specify whether its recovering capacity is improved by physical exercise, 5-week
      old male Wistar rats (287.07 g +/- 10.65 SD) were tail suspended for 14 days,
      then returned to either normal weight-bearing (R) or controlled physical exercise
      for 28 days (R + E). Bone mineral density (BMD) was measured in three parts of
      the femur. Using histomorphometric analysis, bone mass and architecture were
      estimated in the primary (1 degree sp) and secondary spongiosa (2 degrees sp) of
      the proximal tibial metaphysis. Bone cellular parameters were measured in the 2
      degrees sp of the tibia. Tail suspension induced a significant decrease in BMD, 2
      degrees sp bone mass, mineral apposition rate, and bone formation rate and marked
      alterations of the trabecular network. In R rats, BMD was still significantly
      decreased, except in the distal part of the femur. Long-bone lengthening was
      significantly altered. The 2 degrees sp bone mass returned to the age-matched
      control values; however, the trabeculae were still significantly thinner and bone
      resorption was significantly higher. R + E rats had a normal long bone
      lengthening and a significant increase in 2 degrees sp bone mass and trabecular
      thickness when compared with R rats. Bone resorption was significantly depressed,
      and osteoid surfaces and thickness were significantly increased. Thus, although
      bone mass returns to normal values in the R group, trabecular alterations
      persist.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7639119
TI  - Differences in calcium absorption and kinetics between black and white girls aged
      5-16 years.
AB  - To assess racial differences in calcium (Ca) metabolism, we measured Ca
      absorption and kinetics in 89 girls (38 black and 51 white) aged 4.9-16.7 years
      using a dual-tracer stable isotope technique. We found significantly greater
      rates of fractional (0.44 +/- 0.13 vs. 0.25 +/- 0.08, p < 0.0001) and total
      calcium absorption (406 +/- 142 vs. 234 +/- 82 mg/day, p < 0.0003) in black than
      in white postmenarcheal girls. Fractional absorption of Ca was also greater in
      black than in white premenarcheal girls (0.39 +/- 0.14 vs. 0.30 +/- 0.10, p =
      0.01). Fractional absorption of Ca was more closely correlated to Ca intake in
      white (r = -0.42, p = 0.002) than in black girls (r = -0.25, p = 0.14). Urinary
      Ca excretion was significantly lower in pre- but not postmenarcheal black girls
      than in white girls. Calcium kinetic values associated with bone calcium
      deposition were greater in black girls, indicating a greater rate of bone Ca
      deposition in both pre- and postmenarcheal black girls. These results suggest
      that the greater bone mass accumulated during childhood and adolescence in black
      than in white females is due, in part, to greater rates of Ca absorption in black
      girls.

PMID- 7639120
TI  - The influence of volumetric tumor doubling time, DNA ploidy, and histologic grade
      on the survival of patients with intracranial astrocytomas.
AB  - PURPOSE: To improve the prediction of individual survival in patients with
      intracranial astrocytomas through the analysis of volumetric tumor doubling time
      (VDt) and DNA ploidy. METHODS: A pilot study was retrospectively conducted on a
      group of 25 patients with intracranial astrocytomas in whom recurrent and/or
      progressive disease was observed on serial contrast-enhanced CT or MR
      examinations. VDt was computed using two or more data points from a
      semilogarithmic plot of tumor volume versus time. Size-adjusted survival was
      calculated using a method based on VDt and initial tumor volume to decrease the
      lead time bias attributable to differing tumor sizes at presentation. RESULTS:
      Slower VDt was associated with significantly longer survival and size-adjusted
      survival as determined by a univariate Cox proportional hazard analysis.
      Aneuploidy was a significant indicator of poor survival. Aneuploid and
      multiclonal astrocytomas had poor size-adjusted survivals compared with diploid
      astrocytomas. Grade IV astrocytomas had significantly poorer survival and size
      adjusted survival compared with lower grades (I to III), which individually were
      not significantly correlated. However, grade IV histology was not a significant
      independent predictor of size-adjusted survival in a multivariate Cox model,
      whereas VDt and DNA ploidy remained significant. VDt also had a significant
      direct linear correlation to survival and size-adjusted survival. CONCLUSIONS:
      VDt and DNA ploidy were more sensitive than histologic grading as indicators of
      individual survival. Initial tumor size needs to be considered when staging and
      assessing survival in patients with intracranial astrocytomas.

PMID- 7639121
TI  - Patterns of growth of gliomas.

PMID- 7639122
TI  - Diffuse leptomeningeal gliomatosis with osteoblastic metastases and no evidence
      of intraaxial lesions.
AB  - An autopsy-proved case of cerebral and medullary leptomeningeal gliomatosis and
      diffuse osteoblastic metastases without evidence of intraaxial tumor is
      described. MR findings included diffuse thickening of the cerebral and medullary
      leptomeninges on T1-weighted, proton density-weighted, and T2-weighted images and
      abnormal enhancement of the sulci and cisterns of the cerebrum, brain stem,
      cerebellum, and medulla on postcontrast T1-weighted images. MR also showed
      several areas of replacement of the normal bone marrow of the skull. No
      intraaxial lesion was seen.

PMID- 7639123
TI  - MR staging of acute dural sinus thrombosis: correlation with venous pressure
      measurements and implications for treatment and prognosis.
AB  - PURPOSE: To correlate parenchymal brain changes, venous sinus pressure
      measurements, and outcome in 29 patients with acute dural sinus thrombosis.
      METHODS: A retrospective review of 29 patients with angiographically proved acute
      dural sinus thrombosis was made from January 1989 to December 1993. MR
      examinations were performed on either a 0.5- or 1.5-T superconductive scanner in
      multiple planes. Direct dural sinus venography, cerebral angiography, and MR
      venography were performed. Venous sinus pressure measurements were obtained in 11
      of 29 patients. RESULTS: We identified five distinct stages of brain parenchymal
      changes; each stage correlated with increasing intradural sinus pressure. The
      pressures measured in this study ranged from 20 to 50 mm Hg. Brain parenchymal
      changes were reversible up to stage III if thrombolytic treatment was performed.
      Beyond stage III, there were some residual changes, even after thrombolysis. All
      stage V patients died. CONCLUSION: Acute dural sinus thrombosis leads to distinct
      stages of parenchymal changes, the severity of which depends on the degree of
      venous congestion, which, in turn, is closely related to intradural sinus
      pressure. As intradural sinus pressure increases, progression from mild
      parenchymal change to severe cerebral edema and/or hematoma may occur if
      thrombolysis is delayed.

PMID- 7639124
TI  - Collagen microbeads: experimental evaluation of an embolic agent in the rete
      mirabile of the swine.
AB  - PURPOSE: To evaluate the histologic and angiographic effects of collagen
      microbeads as an embolic agent in the swine rete mirabile. METHODS: Human
      collagen particles (380 +/- 100 microns) of spheroidal shape and smooth surface
      were used to embolize the rete mirabile in five swine. Control angiograms and
      pathologic examinations were obtained immediately and sequentially from 3 to 35
      days after embolization. RESULTS: The collagen particles were easy to inject
      through microcatheters. Embolization was always angiographically complete and
      persistent for at least 5 weeks. Histologic studies showed occlusion of 25% to
      50% of the rete vessels. After 3 and 5 weeks' follow-up, transmural and
      adventitial chronic inflammation was present. Inflammatory infiltrates included
      lymphohistiocytic cells and scattered eosinophils. The foreign-body giant-cell
      reaction was pronounced. No evidence of angionecrosis or focal hemorrhage was
      shown. CONCLUSIONS: Collagen microbeads are a promising experimental embolic
      agent, with potential future applications in humans.

PMID- 7639125
TI  - Experimental maxillofacial arterial chemoembolization with encased-cisplatin
      ethylcellulose microspheres.
AB  - PURPOSE: To compare chemoembolization with conventional chemotherapy and explore
      the possibility of chemoembolization in the oral and maxillofacial region using
      encased-anticancer-drug microspheres. METHOD: Six mongrel dogs were divided into
      two equal groups, an experimental group undergoing maxillofacial arterial
      chemoembolization with cisplatin encased in ethylcellulose microspheres, and a
      control group undergoing the conventional chemotherapy with cisplatin. The
      peripheral venous cisplatin concentration and the cisplatin concentration at the
      local tissue were determined. RESULT: The experiment showed a significant
      difference in the peripheral venous cisplatin concentration between the two
      groups and between the time period. There was also a significant interaction
      between groups and time. The peak concentration in the experimental group
      appeared 12 to 24 hours after chemoembolization. The peak concentration in the
      control group appeared immediately after the anticancer drug was infused. There
      was a significant difference in the concentration in the local tissue between the
      two groups, when all time periods were aggregated. CONCLUSION: Compared with
      conventional chemotherapy, the maxillofacial arterial chemoembolization with
      cisplatin encased in ethylcellulose microspheres significantly decreases the
      cisplatin concentration in the peripheral venous circulation and increases the
      concentration in the local tissues, allowing for the possibility of target cancer
      therapy.

PMID- 7639126
TI  - Self-expanding nitinol stents in canine vertebral arteries: hemodynamics and
      tissue response.
AB  - PURPOSE: To evaluate the hemodynamics and tissue response associated with stent
      placement in low-flow-velocity arteries. METHODS: Six self-expanding nitinol
      stents (5.5 mm caliber) were implanted transfemorally within the proximal
      segments of vertebral arteries (2.5 mm diameter) in six adult dogs during
      anticoagulative protection. RESULTS: Control angiograms demonstrated patency and
      20% dilatation of all stented arteries. One artery was partially thrombosed 1
      week later and subsequently showed a 50% stenosis. Throughout the observation
      period (4 to 9 months after stenting), the other five arteries remained patent
      without significant narrowing (< or = 15%). Small cervical muscle branches
      originating from the vertebral arteries within the stented segments remained
      patent. No major branch occlusions of the vertebrobasilar system were detected.
      Stent migration or kinking did not occur. MR studies of the brain 4 months after
      implantation revealed no infarcted areas. These findings were confirmed with
      brain sections. Stented artery specimens showed delayed stent dilatation. A
      comparison of the total mean thickness of intima covering the five 30- to 40-mm
      stents removed at 4, 6, and 9 months showed no significant difference (338, 332,
      and 389 microns, respectively). Histologic findings verified the macroscopic
      impression of a thicker intima at the inner curve of the stented artery segments
      and at the junctions of the stent filaments. The shortest (10 mm) stent had the
      thinnest neointimal growth (155 microns). Stented vessels showed compression of
      the media with atrophy, but without necrosis or perforation. Scanning electron
      photomicrographs revealed intact endothelial cell linings with typical elongated
      cells. CONCLUSIONS: No significant risk of thromboembolic events exists after
      implanting these nitinol stents in nonatherosclerotic vertebral arteries in dogs.
      Thicker neointimal growth after stenting may result from either low wall shear
      stress with possible flow separation or from changes in the shape and size of the
      stent, or both.

PMID- 7639127
TI  - Giant serpentine aneurysms: radiographic features and endovascular treatment.
AB  - PURPOSE: To describe the characteristic CT, MR, and angiographic features of
      giant serpentine aneurysms and discuss their endovascular treatment. METHODS:
      Thirteen patients with giant serpentine aneurysms were studied at our institution
      in the last 3 years. They all underwent CT and MR studies as well as cerebral
      angiography. More recently, some of the patients were studied with MR
      angiography. Seven patients had endovascular occlusion of the giant serpentine
      aneurysms, 3 with N-butyl cyanoacrylate, 2 with Guglielmi detachable coils, and 2
      with detachable balloons. RESULTS: Giant serpentine aneurysms mimic cerebral
      neoplasms on CT and MR studies; they are often associated with mass effect and
      adjacent edema, and they enhance with contrast medium. The cerebral angiogram
      shows a residual irregular lumen of the partially clotted aneurysm, which
      continues into normal branches supplying the distal arterial territory. Six
      patients were treated successfully with an endovascular approach consisting of
      complete and permanent occlusion of the parent artery. CONCLUSION: Giant
      serpentine aneurysms from a subgroup of large intracranial aneurysms that have
      specific CT, MR, and angiographic features, which should be recognized before
      their treatment. The endovascular treatment of the aneurysm consists of permanent
      occlusion of the parent artery.

PMID- 7639128
TI  - Giant serpentine aneurysms: a review and presentation of five cases.
AB  - We present five cases of giant serpentine aneurysms (large, partially thrombosed
      aneurysms containing tortuous vascular channels with a separate entrance and
      outflow pathway) and review 28 cases reported in the literature. Giant serpentine
      aneurysms should be considered as a subgroup of giant aneurysms, distinct from
      saccular and fusiform varieties, given their unique clinical presentation and
      radiographic features.

PMID- 7639129
TI  - Severe symptomatic vasospasm after rupture of an arteriovenous malformation.
AB  - A 31-year-old woman had intracerebral and intraventricular hemorrhage from an
      arteriovenous malformation. Vasospasm of the internal carotid arteries developed
      and was treated with angioplasty. On initial CT scans, only traces of blood were
      seen in the basal cisterns; thus, the development of symptomatic vasospasm was an
      unexpected complication.

PMID- 7639130
TI  - Hemimegalencephaly and intractable epilepsy treated with embolic hemispherectomy.
AB  - A patient with hemimegalencephaly and intractable epilepsy underwent a
      preoperative embolic hemispherectomy. A seizure-free interval of 1 year followed
      the embolization procedure. In addition, the procedure was thought to be
      beneficial in limiting blood loss during a subsequent surgical hemispherectomy.

PMID- 7639131
TI  - Endovascular treatment of epistaxis in a patient with tuberculosis and a giant
      petrous carotid pseudoaneurysm.
AB  - A 31-year-old man with pulmonary tuberculosis who did not have human
      immunodeficiency virus had massive epistaxis from a giant petrous internal
      carotid artery pseudoaneurysm. Endovascular trapping of the aneurysm was
      performed, curing the epistaxis. MR showed multiple enhancing brain lesions that
      resolved with additional antituberculous drug therapy.

PMID- 7639132
TI  - A comparison of functional MR activation patterns during silent and audible
      language tasks.
AB  - PURPOSE: To compare word generation tasks performed silently and aloud as
      paradigms for functional MR. METHODS: Images were obtained at 1.5 T, with
      echoplanar acquisition in nine subjects performing word generation aloud or
      silently. Functional images created from the echoplanar images by means of cross
      correlation techniques were superimposed on anatomic reference images. The
      location of activation from the two tasks was tabulated; the number of activated
      pixels in each region from the two tasks was compared. RESULTS: Both silent and
      aloud word generation produced activation in the inferior frontal lobes,
      sensorimotor cortex regions, supplementary motor areas, and anterior cingulate
      gyri, predominantly in the dominant hemisphere. Significantly more activated
      pixels and fewer artifacts were detected with silent word generation than with
      word generation aloud. CONCLUSION: Word generation silently or aloud produce
      activation in the brain. Greater activation can be detected in the left frontal
      lobe with silent word generation, although the subject's performance of the task
      cannot be monitored independently during silent word generation.

PMID- 7639133
TI  - Neuroradiology in Boston: historical beginnings.

PMID- 7639134
TI  - Common carotid artery occlusion: evaluation with duplex sonography.
AB  - PURPOSE: To demonstrate the efficacy of carotid duplex ultrasound to diagnose
      common carotid artery occlusion (CCAO) and to define the clinical features of
      CCAO. METHODS: We reviewed 5400 carotid duplex ultrasonograms obtained over a 7
      year period for suspected carotid artery disease. In cases of CCAO, medical
      records were reviewed. RESULTS: Thirteen cases (0.24%) of CCAO were diagnosed by
      carotid duplex ultrasonography, including five cases of isolated CCAO. Seven
      cases were proved by cerebral angiography. Cerebral angiography failed to
      demonstrate patent internal carotid arteries in two cases of isolated CCAO. Mean
      age of onset was 67 +/- 9 years. The main clinical presentation was stroke in
      nine cases (69%). The most common vascular risk factors were hypertension (62%)
      and heart diseases (54%). Three patients had a history of radiation therapy to
      the neck. Two of five patients with isolated CCAO had major stroke, with good
      recovery in one, whereas five of eight patients with CCAO had major stroke; among
      them, only one had good recovery. CONCLUSION: Patients with isolated CCAO may
      have a better outcome than patients with CCAO. Duplex sonography, particularly
      with color-coded flow imaging, provides an accurate examination to define the
      patency of the arteries distal to the carotid bifurcation. The clinical features
      of CCAO are similar to those of internal carotid artery occlusion except for the
      low prevalence of CCAO.

PMID- 7639135
TI  - Role of vasogenic edema and tissue cavitation in ischemic evolution on diffusion
      weighted imaging: comparison with multiparameter MR and immunohistochemistry.
AB  - PURPOSE: To examine the mechanisms of further evolution that occurs from the
      early to late phase after initial changes in diffusion-weighted imaging after
      cerebral ischemia. METHODS: Sprague-Dawley rats were subjected to middle cerebral
      artery occlusion. Diffusion-, proton density-, T1- and T2-weighted imaging were
      performed on days 0, 2, and 6. Histologic examination (IgG, glial fibrillary
      acidic protein, and cresyl violet staining) was done after scanning. RESULTS:
      Apparent diffusion coefficients (ADCs) in the ischemic hemisphere were
      significantly decreased on day 0. Thereafter, ADCs increased over time and became
      significantly higher than the contralateral side by day 6. Changes in basal
      ganglia occurred more rapidly than in cortex. Proton density-, T1-, and T2
      weighted scans showed maximal changes on day 2. From day 0 to day 2, there are
      significant correlations between changes in ADC and changes in T1-weighted
      signals and T2-weighted signals. Histologic exam showed early neuronal injury on
      day 0, intense gliotic activity and protein leakage associated with infarction
      and edema on day 2, and cavitation in severely infarcted areas on day 6.
      CONCLUSION: After initial reduction of ADC, the subsequent increase in ADC values
      on day 2 may be associated with vasogenic edema and cell lysis. Later elevations
      in ADC may be related to cavitation of infarcted tissue.

PMID- 7639136
TI  - Congenital hypothyroidism: assessment with ultrasound.
AB  - PURPOSE: To determine the clinical utility of cervical ultrasound in patients
      suspected of having congenital hypothyroidism. METHODS: Thirty-seven patients
      with suspected congenital hypothyroidism underwent ultrasound and scintigraphic
      evaluation of the thyroid anatomy, morphology, and function. The ultrasound
      findings and laboratory data were compared with the standard-of-reference
      scintigraphic findings and laboratory data for diagnosing specific causes in
      those patients, and prognosis was correlated with the ultrasound findings.
      RESULTS: Ultrasound was not reliable for detecting ectopia (n = 8) or
      differentiating ectopia from aplasia (n = 1). Ultrasound showed ectopia in six
      (four in the mouth floor and two in the tongue base) of eight cases (75%
      sensitivity). Ultrasound did not show one ectopia in the floor of mouth because
      its echogenicity was similar to that of surrounding tissues. A second ectopia, in
      the hypopharynx, was missed because of hindrance of the laryngeal air.
      Radioactive iodine uptake and scintigraphy was required for the patients with
      enlarged glands in the normal place to differentiate dyshormonogenesis from other
      categories. Specific causes were diagnosed correctly with ultrasound findings and
      laboratory data alone in all of the 20 patients who had hemiaplasia or small or
      normal-size glands in the normal location. Incidences of heterogeneity and
      hypoechogenicity of the thyroid gland in patients with prolonged clinical course
      (whose replacement therapy or follow-up extended for more than 1 year) were
      significantly higher than those in patients with short clinical course.
      CONCLUSION: Ultra-sound can obviate the need for scintigraphy in more than half
      (54%) of patients with possible congenital hypothyroidism. Ultrasound has a
      potential to predict prognosis of these patients.

PMID- 7639137
TI  - MR of cystic aberrant cervical thymus.
AB  - The clinical, MR imaging, surgical, and histologic findings in two cases of
      cystic aberrant cervical thymus were reviewed. Aberrant cervical thymic tissue
      was sharply circumscribed and extended deep to the posterior pharyngeal wall at
      the level of the piriform sinus in both cases. Both lesions had cyst contents
      that were of increased signal intensity on T1-weighted images. Solid components
      displayed MR signal characteristics identical to normal thymus.

PMID- 7639138
TI  - Polycystic disease of the parotid glands.
AB  - A 31-year-old woman had bilateral swelling of the parotid glands at 4 months of
      pregnancy. MR imaging showed marked enlargement of the parotid glands with
      increased signal on images with long repetition times. A diagnosis of polycystic
      disease of the parotid gland was made after biopsy and histologic examination.
      The radiographic and histologic features of this rare disease are discussed.

PMID- 7639139
TI  - Nasopharyngeal nonossifying variant of ossifying fibromyxoid tumor: CT and MR
      findings.
AB  - The CT and MR findings of a nasopharyngeal nonossifying variant of an ossifying
      fibromyxoid tumor are presented. The findings are radiographically
      indistinguishable from more common malignant neoplasms encountered in this
      region. The tumor was isointense with muscle on T1-weighted images. On proton
      density- and T2-weighted images, the mass was mostly isointense with gray matter
      but contained some areas of lower intensity that might reflect the fibrous tissue
      component. The tumor eroded through the floor of the middle cranial fossa.

PMID- 7639140
TI  - Magnetic susceptibility artifacts on high-resolution MR of the temporal bone.
AB  - PURPOSE: To determine whether signal variations and subtle anatomic deformities
      observed in high-resolution MR studies of temporal bones were caused by the large
      susceptibility differences at air-fluid interfaces near the round and oval
      window. METHODS: A systematic study of healthy subjects and plastic phantoms was
      conducted. The phantom consisted of a series of cylindrical holes of various
      small sizes within a solid block of plastic. These holes were partially filled
      with water and then covered with a reservoir of gelatin to simulate the otic
      capsule air-water interfaces. On a 1.5-T system, T2-weighted fast spin-echo
      images and three-dimensional Fourier transform gradient acquisition in steady
      state images were obtained using dedicated phased-array radio frequency coils.
      The directions of the frequency and in-plane phase-encoding gradients were
      swapped, and the receiver bandwidth was changed to demonstrate the dependence of
      the artifacts on these parameters. RESULTS: The phantom images confirmed and
      characterized artifacts consistent with magnetic susceptibility differences at
      the air-water interfaces. There is a combination of signal loss, misregistration
      in the frequency-encoding direction, and high signal foci related to the air
      water interfaces. Furthermore, the artifacts were worse with narrower receiver
      bandwidth. Similar consistent artifact patterns were seen near the oval and round
      windows in studies of healthy subjects. CONCLUSIONS: In high-resolution MR
      imaging there are significant deformities in the display of the normal anatomy
      because of magnetic susceptibility.

PMID- 7639141
TI  - Geniculate ganglion meningiomas: CT and MR appearances.

PMID- 7639142
TI  - Detection of cerebrospinal fluid metastasis: CT myelography or MR?
AB  - PURPOSE: To determine the sensitivity of contrast MR versus myelography followed
      by CT in the detection of cerebrospinal fluid metastases in children with primary
      central nervous system tumors. METHODS: Thirty-three patients who had primary
      central nervous system malignancies had spinal MR with gadolinium within 2 weeks
      of a myelogram followed by CT. MR technique included T1-weighted image sequences
      of the entire spine with and without gadolinium. CT scans were routinely
      performed at T-12 to L-2, L-4 to S-1, and foramen magnum to C-2. All studies were
      reviewed blindly; the number, character, and location of all metastases was
      recorded and the results of the two studies compared. Cerebrospinal fluid
      cytologic findings were recorded for each patient, and compared with the results
      of the imaging studies. RESULTS: Seven of the 33 patients had metastases
      detected; metastases were seen on both MR and myelography followed by CT.
      However, MR showed 24 lesions and myelography followed by CT showed only 15. When
      a lesion was seen on both MR and myelography followed by CT, the MR was usually
      more convincing. Superficial lesions seen on MR sometimes would be missed on
      myelography followed by CT. Both MR and myelography followed by CT were quite
      sensitive in the detection of small lesions (2 to 3 mm) when present on spinal
      nerve roots. Whereas MR showed multiple lesions not seen on myelography followed
      by CT, CT failed to show any metastases not seen on MR. Imaging studies showed
      metastases in 3 patients who had normal cytologic findings. CONCLUSIONS: MR shows
      significantly more cerebrospinal fluid metastases than myelography followed by
      CT.

PMID- 7639143
TI  - Primary osseous amyloidoma causing spinal cord compression.
AB  - The myelographic, CT, and MR findings of a rare localized primary bone amyloidoma
      causing upper thoracic spinal cord compression are presented. Imaging showed a
      large, calcified mass centered in the posteromedial portion of the left second
      rib that invaded the second thoracic vertebra and the spinal canal.

PMID- 7639144
TI  - Unusual fracture dislocation of the craniovertebral junction.

PMID- 7639145
TI  - Spontaneous resolution of a Chiari I malformation: MR demonstration.
AB  - The MR findings in a case of a Chiari type I malformation that resolved
      spontaneously over a 4-year period are presented. Differential growth of the
      skull and spine might have accounted for the resolution of this anomaly.

PMID- 7639146
TI  - Skull-base meningoencephalocele presenting as a unilateral neck mass in a
      neonate.

PMID- 7639147
TI  - Tumoral multiple sclerosis of the cerebellum in a child.
AB  - We present a case of cerebellar tumoral multiple sclerosis in an 11-year-old girl
      and emphasize these two features: (1) Tumoral multiple sclerosis can occur within
      the posterior fossa and should be strongly considered in the differential
      diagnosis of mass lesions of the posterior fossa when typical white matter
      lesions are seen on T2-weighted images. (2) Tumoral multiple sclerosis can
      demonstrate ring enhancement on MR.

PMID- 7639148
TI  - MR of the brain in mitochondrial myopathy.
AB  - PURPOSE: To determine the spectrum of MR findings in patients with mitochondrial
      myopathy and correlate them with central nervous system symptoms and signs.
      METHODS: We performed a prospective evaluation of the MR findings of eight
      patients with mitochondrial myopathy (three with Kearns-Sayre syndrome and five
      with chronic progressive external ophthalmoplegia), six of whom had central
      nervous system symptoms or signs (ataxia, sensorineural hearing loss, or
      cognitive dysfunction). RESULTS: All six patients with neurologic symptoms or
      signs had multiple abnormal MR findings, whereas patients without neurologic
      symptoms had either normal MR findings (one patient) or the solitary finding of
      cortical atrophy (one patient). Abnormal MR findings consisted of cerebral
      cortical atrophy (seven patients), cerebellar atrophy (six patients), and
      hyperintense signal abnormalities on T2-weighted images within the cerebral white
      matter (three patients), cerebellar white matter (one patient), basal ganglia
      (three patients), brain stem (one patient), and thalamus (one patient). In two
      patients, the cerebral white matter signal abnormalities were primarily
      peripheral and involved the arcuate fibers. All patients with ataxia had abnormal
      cerebellar findings on MR imaging, but there was poor correlation between other
      neurologic features and MR findings. CONCLUSIONS: Cerebral and cerebellar atrophy
      are the most common MR findings in Kearns-Sayre syndrome and chronic progressive
      external ophthalmoplegia. White matter and deep gray nuclei abnormalities,
      presumed to result from the diffuse spongiform encephalopathy reported in these
      patients, can also be seen. Patients with abnormal neurologic findings typically
      have multiple abnormalities on MR imaging, which frequently do not correlate with
      specific symptoms.

PMID- 7639149
TI  - CT appearance of a traumatic cataract.
AB  - We describe a case of a traumatic cataract that presented on CT as a hypodense
      lens with a hyderdense rim. The finding reflects the pathogenesis of this entity:
      a capsular tear and consequent entry of fluid into the lens.

PMID- 7639150
TI  - Bone erosion caused by sinonasal cavernous hemangioma: CT findings in two
      patients.
AB  - We report two cases of cavernous hemangioma originating in the sinonasal cavity.
      Although CT showed some enhancing areas within both tumors, the substantial bone
      destruction caused by these tumors made it difficult to differentiate them from
      the more common malignant epithelial tumors. Angiography was performed in one
      patient and showed characteristic pooling of contrast material.

PMID- 7639151
TI  - MR of central nervous system actinomycosis.

PMID- 7639152
TI  - Annotated bibliography.

PMID- 7639153
TI  - Improved identification of coronary artery disease in patients with left bundle
      branch block by use of dobutamine stress echocardiography and comparison with
      myocardial perfusion tomography.
AB  - This study compared the efficacy of dobutamine stress testing using 2-dimensional
      echocardiography and perfusion tomography for the noninvasive identification of
      coronary artery disease (CAD) in patients with left bundle branch block (LBBB).
      Twenty-four patients with permanent, complete LBBB (11 with previous myocardial
      infarction) were studied prospectively with dobutamine echocardiography and
      perfusion tomography. The presence of > 50% luminal diameter coronary stenosis
      was compared with the presence of dobutamine-induced fixed or reversible
      perfusion defects, and with resting or dobutamine-induced abnormalities of wall
      thickening. For each test, the left anterior coronary artery territory was
      compared with the circumflex and/or right coronary artery. Significant CAD was
      found in the left anterior descending coronary artery in 12 patients; all (100%)
      were identified by perfusion imaging, and 10 (83%, p = NS) by 2-dimensional
      stress echocardiography. In the 12 patients without left anterior descending CAD,
      scintigraphy was also positive in all (specificity: 0%), and echocardiography in
      only 1 (specificity: 92%, p < 0.01). The diagnostic accuracy was 50% and 87% (p <
      0.05), respectively. This low specificity of perfusion tomography was improved by
      requiring an associated apical defect to indicate left anterior descending CAD
      and was corrected by restricting the diagnosis of coronary disease to those
      patients with partially reversible defects. In the circumflex and/or right
      coronary artery territory, sensitivity and specificity were similar using both
      techniques. We conclude that dobutamine-stress echocardiography is a specific and
      accurate test for the noninvasive identification of CAD, even in the left
      anterior descending artery territory of patients with LBBB.

PMID- 7639154
TI  - The genotype of the angiotensin-converting enzyme gene and global left
      ventricular dysfunction after myocardial infarction.
AB  - We examined the relation between the genotype of the angiotensin-converting
      enzyme (ACE) gene and the development of left ventricular dysfunction, as
      assessed by biplane left ventriculograms, after myocardial infarction. Seventy
      nine patients (deletion homozygote [DD] = 13; insertion/deletion heterozygote
      [ID] = 38; insertion homozygote [II] = 28) underwent cardiac catheterization
      twice for reevaluation of percutaneous transluminal coronary angioplasty.
      Subjects who had their first cardiac catheterization within 2 months from the
      onset of myocardial infarction were enrolled. The second cardiac catheterization
      was performed from 4 to 7 months after the first cardiac catheterization. ACE
      genotypes were determined by using the polymerase chain reaction. Ejection
      fraction, and end-diastolic and end-systolic volume indexes at the first cardiac
      catheterization were not significantly different among the 3 groups. The end
      diastolic volume index at the second cardiac catheterization was not
      significantly different among the 3 groups. Ejection fractions (mean +/- SD) at
      the second catheterization in the 3 groups were 0.51 +/- 0.15 (DD), 0.56 +/- 0.12
      (ID), and 0.62 +/- 0.09 (II) (p = 0.02), and were significantly lower in the DD
      group than in the II group. The end-systolic volume indexes (mean +/- SD) were 46
      +/- 21 (DD), 43 +/- 24 (ID), and 30 +/- 14 (II) ml/m2 (p = 0.01), and were
      significantly greater in the DD and ID groups than in the II group.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7639155
TI  - Comparison of early invasive and conservative treatments in patients with
      anterior wall non-Q-wave acute myocardial infarction.
AB  - To compare the long-term prognosis of a group of patients treated by an early
      invasive approach after a non-Q-wave anterior wall acute myocardial infarction
      (AMI) with a similar group treated conservatively, data from 110 consecutive
      patients with non-Q-wave AMI were retrospectively obtained from 3 different
      hospitals: (1) a hospital with coronary angioplasty and coronary bypass
      facilities favoring on early invasive approach, (2) a hospital with a
      catheterization laboratory and no coronary angioplasty or coronary bypass
      facilities, and (3) a community hospital without a catheterization laboratory.
      Patients were divided according to the presence or absence of an early invasive
      approach: those who had undergone in-hospital catheterization and
      revascularization (n = 55) and those with a conservative approach (n = 55). The
      early invasive approach resulted in a significant decrease in major events. The
      rate of recurrent myocardial infarction was 29% in the conservative group versus
      7.2% in the invasive group (p = 0.025). Survival rate curves at 3-year follow-up
      showed significant differences in mortality (p = 0.001), recurrent myocardial
      infarction (p = 0.002), recurrent angina pectoris (p = 0.001), and development of
      congestive heart failure (p = 0.05). Multivariate analysis disclosed the early
      invasive approach to be an independent predictor for decreasing the likelihood of
      recurrent infarction by 86% (odds ratio 0.14, confidence intervals 0.04 to 0.48,
      p = 0.0006), and for decreasing the likelihood of recurrent angina by 66% (odds
      ratio 0.34, confidence intervals 0.18 to 0.63, p < 0.005). The early invasive
      strategy may result in an improved outcome in the treatment of patients with non
      Q-wave anterior wall AMI compared with patients treated conservatively.

PMID- 7639156
TI  - Can nitroglycerin convert effort-induced angina in men into silent myocardial
      ischemia?
AB  - The relief of anginal pain with nitroglycerin may not correspond to the
      disappearance of ischemia. To evaluate the possible lack of the elimination of
      ischemia with sublingual nitroglycerin, we studied 25 male patients with stable
      angina pectoris who underwent exercise stress testing with recording of blood
      pressure, pulse, and ST-segment displacement. The stress test was repeated 30
      minutes after administration of 0.4 mg of sublingual nitroglycerin. All 25
      patients had angina and ischemic ST-segment changes in the first stress test. On
      repeat stress testing, 15 patients had angina and ST-segment changes, 2 patients
      had angina but no ST-segment changes, and 4 patients had no ST-segment changes
      and no angina. Four patients, however, had no angina but persistent ischemic ST
      segment changes suggesting that angina was converted into silent ischemia. The
      mean exercise duration was 311 +/- 66 seconds before and 421 +/- 81 seconds after
      the nitroglycerin test. Peak heart rate and systolic blood pressure before the
      nitroglycerin stress test were 109 +/- 18 and 155 +/- 23 mm Hg; in the repeat
      stress test, they increased to 123 +/- 21 and 162 +/- 20 mm Hg, respectively.

PMID- 7639158
TI  - Relative importance of electrode placement over number of channels in transient
      myocardial ischemia detection by Holter monitoring.
AB  - To compare the efficacy of 3-channel ambulatory electrocardiographic monitoring
      (Holter monitoring) with 2-channel Holter monitoring in the detection of
      transient myocardial ischemia (TMI), channels CM2, CM5, and modified II were
      studied. Sixty patients with documented coronary artery disease underwent 48-hour
      Holter monitoring during their normal daily life, followed by exercise stress
      testing in the laboratory monitored by means of radionuclide ventriculography and
      standard 12-lead electrocardiography. Analysis revealed that 3-channel Holter
      monitoring identified 24 patients with a total of 205 TMI episodes and a total
      ischemic burden of 371.00 mV-min. By itself, CM2 would have detected only 3
      patients (13% of the TMI population), 6 TMI episodes (3% of the total TMI
      episodes), and a 2.4 mV-min ischemic burden (0.7% of the total ischemic burden).
      Modified II alone would have identified 17 patients (71% of the TMI population),
      160 TMI episodes (78% of the total TMI episodes), and 307.24 mV-min of the
      ischemic burden (82% of the total ischemic burden). The combination of
      CM5/modified II identified 23 patients (96% of the TMI population), 201 TMI
      episodes (98% of the total TMI episodes), and 370.44 mV-min of the ischemic
      burden (98% of the total ischemic burden). These findings suggest that the
      electrode placement is more important than the absolute number of channels in the
      detection of TMI by Holter monitoring.

PMID- 7639157
TI  - Correlation of donor characteristics with transplant coronary artery disease as
      assessed by intracoronary ultrasound and coronary angiography.
AB  - The mechanisms responsible for transplant coronary artery disease (CAD) and its
      predisposing factors remain incompletely understood. The influence of donor
      characteristics as predisposing factors has not been studied systematically. We
      examined the correlation of donor demographic, clinical, and immunologic
      parameters with transplant CAD assessed by both intracoronary ultrasound (ICUS)
      and coronary angiography in 116 heart transplant recipients (age 44.7 +/- 12.0
      years) studied 3.4 years (range 1.0 to 14.6) after transplantation. Quantitative
      ultrasound data were obtained by calculating mean intimal thickness from several
      distinct coronary sites. Coronary angiograms were categorized visually as normal
      or showing any transplant CAD. By multivariate regression analysis, donor
      undersize of > 20% of recipient weight (p < 0.02) and duration after
      transplantation (p < 0.005) were independently correlated with the amount of ICUS
      intimal thickness (r = 0.36, p = 0.0007), and older donor age with angiographic
      evidence for the disease (r = 0.34, p < 0.006). In a subgroup analysis of the 39
      patients studied 1 year after transplantation, white donor race (p < 0.05), fewer
      human leukocyte antigen-DR mismatches (p < 0.002), shorter ischemic time (p <
      0.04), and donor smoking history (p < 0.02) were independent predictors for
      severity of ICUS intimal thickening (r = 0.92, p = 0.0009); higher donor age (p <
      0.006) and higher arterial partial pressure of oxygen (p < 0.003) were
      independent predictors for angiographic disease (r = 0.67, p < 0.002). In
      conclusion, donor characteristics may contribute to the probably multifactorial
      pathogenesis of transplant CAD.

PMID- 7639159
TI  - Clinical and echocardiographic features of intermittent atrial fibrillation that
      predict recurrent atrial fibrillation. Stroke Prevention in Atrial Fibrillation
      (SPAF) Investigators.
AB  - In addition to antithrombotic therapy, 2 treatment strategies for intermittent
      atrial fibrillation (AF) are evolving: suppression of AF or control of the
      ventricular response during AF. Clinical and echocardiographic features that
      predict recurrent AF may influence the choice of management. In this study,
      clinical, echocardiographic, and electrocardiographic data from 486 patients with
      intermittent AF enrolled in the Stroke Prevention in Atrial Fibrillation studies
      were analyzed. Patients with intermittent AF were younger (p < 0.001), had fewer
      incidences of systemic hypertension (p < 0.007) and heart failure (p < 0.001),
      and had more recent-onset AF than patients with constant AF. They also had a
      smaller mean left atrial diameter, a lower prevalence of a large (> 5 cm) left
      atrium, better left ventricular performance by echo, and less mitral
      regurgitation. After a mean follow-up of 26 months, 51% of patients remained in
      sinus rhythm and 49% of patients developed recurrent AF, including 12% who had
      AF, as seen on all follow-up electrocardiograms. Clinical factors predicting
      recurrent AF were age, heart failure, and myocardial infarction. An enlarged left
      atrium was associated with recurrent intermittent AF; an enlarged left ventricle
      predicted conversion to constant AF. Thus, clinical and echocardiographic
      parameters predict recurrent AF in patients with intermittent nonvalvular AF.

PMID- 7639160
TI  - Efficacy and safety of radiofrequency catheter ablation of left-sided accessory
      pathways through the coronary sinus.
AB  - Radiofrequency catheter ablation of left-sided accessory pathways (APs) with the
      use of an endocardial technique carries all potential risks of left heart
      catheterization. We analyzed the determinants of success, efficacy, and safety of
      radiofrequency catheter ablation from the coronary sinus (CS), as a potential
      alternative to the endocardial technique in these patients. Thirteen patients
      (mean age 40 +/- 20 years) with 15 left-sided APs and a history of symptomatic
      supraventricular tachycardia were included in the study. Nine APs were localized
      in the left posteroseptal region, and the remaining 6 in the left free wall.
      Ablation from CS was attempted in 12 patients with 14 APs. In 1 patient ablation
      within the CS was not deemed safe because of a small venous lumen. All 14 APs
      were successfully ablated using either CS ablation alone or combined with the
      endocardial technique. Efficacy of the CS ablation as a primary technique was 56%
      (5 of 9 APs). In 5 additional APs, ablation in the CS eliminated pathway
      conduction after failed endocardial attempts. CS ablation either as a primary or
      a secondary technique eliminated conduction in 10 of 14 APs (71.4%) (group 1). In
      the remaining 4 APs (group 2), the primary CS attempt was unsuccessful and APs
      were ablated with a subsequent endocardial approach. Determinants of success for
      the CS method were local AP to atrial and/or ventricular electrogram amplitude
      ratios > or = 1 (p < 0.05). The success rate of CS ablation was 83% in the left
      posteroseptal APs adjoining the branching point of the middle cardiac vein or a
      CS anomaly.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7639161
TI  - Comparison of the 10-minute supine-30-minute tilt test with 24-hour ambulatory
      blood pressure for the diagnosis of diastolic systemic hypertension.
AB  - A variant of the protracted tilt test, the 10-minute supine -30-minute tilt test
      (10S-30TT), has been proposed by us for the evaluation of blood pressure (BP).
      The present investigation compares parameters of diastolic BP by 3 methods:
      office measurements, 10S-30TT, and 24-hour ambulatory monitoring; the last method
      served as a reference standard. Twenty patients presenting at the office with
      diastolic BP values ranging from 80 to 120 mm Hg (median 90) were studied.
      Statistically significant correlations were observed between the following
      parameters: diastolic office BP and average ambulatory awake diastolic BP (r =
      0.64, p = 0.002); average tilt-test diastolic BP and average ambulatory awake
      diastolic BP (r = 0.69, p = 0.0006); frequency of elevated diastolic BP values
      during the tilt test and frequency of elevated ambulatory awake diastolic BP
      values (r = 0.69, p = 0.0007). Diastolic BP diagnosis scores exhibited strong
      correlation only between the ambulatory and tilt-test diagnosis (kappa = 0.70),
      but not between ambulatory and office BP diagnosis (kappa = 0.50). Based on the
      close correlation between results of the 10S-30TT and ambulatory monitoring in
      the evaluation of diastolic BP, we suggest that the faster and cheaper tilt test
      may serve as a substitute in certain categories of patients.

PMID- 7639162
TI  - Optimal electrode configuration for pectoral transvenous implantable
      defibrillator without an active can.
AB  - A new 83 cm3 implantable cardioverter-defibrillator (ICD) designed for pectoral
      implantation has been implanted most frequently using right ventricular and
      superior vena cava (RV-->SVC) electrodes; a patch electrode (RV-->patch + SVC)
      has been added when necessary to decrease the defibrillation threshold (DFT). The
      goal of this prospective study was to compare biphasic waveform DFTs for 3
      electrode configurations: RV-->patch, RV-->SVC, and RV-->patch + SVC in 25
      consecutive patients. The patch was positioned in a left retro-pectoral pocket,
      and the SVC electrode was positioned with the tip at the junction of the SVC and
      innominate vein. In the first 15 patients, all 3 electrode configurations were
      tested in random order; in the last 10 patients, only the RV-->patch and RV-
      >patch + SVC configurations were tested. In the first 15 patients, the stored
      energy DFT for the RV-->SVC configuration (15.2 +/- 7.7 J) was higher (p < 0.001)
      than the DFT for the RV-->patch configuration (11.3 +/- 6.2 J) and the RV-->patch
      + SVC configuration (10.0 +/- 5.8 J). For all 25 patients, the DFT was lower for
      the RV-->patch + SVC configuration (9.7 +/- 5.1 J) than for the RV-->patch
      configuration (12.4 +/- 6.6 J, p = 0.005). The pathway resistance was highest for
      the RV-->patch configuration (72 +/- 9 omega), lower for the RV-->SVC
      configuration (63 +/- 6 omega, p < 0.01), and lowest for the RV-->patch + SVC
      configuration (46 +/- 3 omega, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7639163
TI  - Nocturnal dosing of a novel delivery system of verapamil for systemic
      hypertension. Verapamil Study Group.
AB  - To evaluate the efficacy and safety of a novel delivery system of physiologic
      pattern release (PPR)-verapamil administered nocturnally to patients with stages
      I and II hypertension using ambulatory blood pressure (BP) monitoring, we
      performed a multicenter (17 centers), double-blind, randomized, placebo
      controlled, parallel-group trial with placebo and 120, 180, 360, and 540 mg of
      verapamil in 287 randomized patients. The delivery system has a delay in the
      release of verapamil for 4 to 6 hours, and then delivers the drug from an osmotic
      pumping system for approximately 12 hours. Patients were dosed at 10 P.M. The
      primary end point was change from baseline in trough diastolic BP assessed by
      ambulatory BP monitoring from 6 to 10 P.M. after 8 weeks of therapy, whereas
      secondary measures included changes from baseline in peak, early morning (6 to 10
      A.M.) systolic and diastolic BP, trough clinic BP, and 24-hour average daytime (8
      A.M. to 8 P.M.) and nighttime (8 P.M. to 8 A.M.) BP. The 180, 360, and 540 mg
      verapamil doses achieved statistically significant reductions in trough (6 to 10
      P.M.) diastolic BP (-3.9 +/- 1.0, -7.8 +/- 1.2, and -10.6 +/- 1.1 mm Hg,
      respectively). Reductions in peak early morning (6 to 10 A.M.) diastolic BP were
      greater (-4.6 +/- 0.9, -13.3 +/- 1.2, and -19.0 +/- 1.2, for 180, 360, and 540
      mg, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7639164
TI  - Alterations of radial artery compliance in patients with congestive heart
      failure.
AB  - Congestive heart failure is accompanied by several hemodynamic alterations. To
      investigate whether these alterations include reduced arterial compliance, we
      studied 25 patients (age 57 +/- 2 years, mean +/- SE) with a mild or severe
      congestive heart failure based on clinical symptoms (New York Heart Association
      class II vs III or IV) and on echocardiographic alterations of left ventricular
      diastolic diameter and ejection fraction. Radial artery diameter and blood
      pressure were continuously measured by Doppler ultrasonography and a finger
      pressure device, respectively. Compliance was calculated by the Langewouters
      formula, and compliance values were derived throughout the systolic-diastolic
      pressure range. The area under the compliance-pressure curve normalized for pulse
      pressure was used to compare compliance values in the various groups. Data were
      obtained both in baseline condition and at the release from a 12-minute brachial
      artery occlusion. Fourteen healthy, age-matched subjects served as controls.
      Compared with the control group, patients with severe congestive heart failure
      showed a reduction of baseline compliance index (-48%, p < 0.01). Furthermore,
      while in control subjects compliance markedly increased after brachial artery
      occlusion (+43%, p < 0.01), in patients with severe congestive heart failure no
      increase occurred. No baseline compliance alteration was seen in patients with
      mild congestive heart failure in whom, however, the postischemic increase in
      compliance was also significantly blunted (-50% vs controls, p < 0.05). Thus,
      arterial compliance and arterial compliance modulation are impaired in congestive
      heart failure. Although more marked in severe congestive heart failure, the
      impairment is manifest in mild congestive heart failure as well.

PMID- 7639165
TI  - Effect of age and surgical technique on symptomatic arrhythmias after the Fontan
      procedure.
AB  - The purpose of this study was to determine the effects of newer Fontan
      modifications (lateral tunnel with or without fenestration) and patient's age at
      surgery on the incidence and impact of symptomatic postoperative early and
      intermediate arrhythmias. Modifications to the Fontan procedure are used to
      decrease postoperative complications, and the Fontan procedure is now being
      performed on younger patients to reduce age-related changes in ventricular
      function. A retrospective review was done of the medical records of 151
      consecutive patients, ranging in age from 1 to 49 years, who underwent a Fontan
      procedure at Texas Children's Hospital between 1987 and 1993. Risk factors were
      identified for early and intermediate arrhythmias. Age at time of the procedure
      was an independent predictor of early atrial arrhythmias (p = 0.03), ventricular
      arrhythmias (p = 0.003), and junctional ectopic tachycardia (JET) (p = 0.05). We
      found that the older the patient at surgery, the higher the incidence of atrial
      and ventricular arrhythmias, whereas the younger the patient, the higher the
      incidence of JET. Using Cox's proportional-hazards model, the risk of
      intermediate atrial arrhythmias after lateral tunnel modification was 1/3 that
      after atriopulmonary connection. Younger patients who underwent the Fontan
      procedure had a lower risk for early atrial and ventricular arrhythmia but an
      increased risk for JET. The lateral tunnel modification can be performed in order
      to reduce the risk of intermediate atrial arrhythmias.

PMID- 7639166
TI  - Comparison of echocardiographic assessment of cardiac hemodynamics in the
      intensive care unit with right-sided cardiac catheterization.
AB  - Estimation of left ventricular filling pressure and cardiac index is important in
      the management of patients requiring right heart catheterization. Doppler
      echocardiography can provide a noninvasive measure of these parameters, but its
      accuracy in individual measurements, predicting hemodynamic subgroups, and in
      tracking serial changes in critically ill patients remains to be elucidated. Left
      ventricular filling pressure and cardiac index were assessed in 49 critically ill
      patients requiring right heart catheterization and Doppler echocardiographic
      studies. Two or more serial studies were performed in 18 of these subjects.
      Patients were placed into 1 of 4 hemodynamic subgroups for each technique based
      on the acquired hemodynamic parameters. Left ventricular filling pressure and
      cardiac index by Doppler echocardiography and right heart catheterization were
      similar (21 +/- 8 vs 20 +/- 8 mm Hg; 3.0 +/- 1.2 vs 2.9 +/- 1.2 L/min/m2,
      respectively) and correlated well with each other (left ventricular filling
      pressure, r = 0.88; cardiac index, r = 0.92). The Doppler technique accurately
      placed 73 of 76 studies into the correct hemodynamic subgroup. The noninvasive
      technique also reliably tracked serial hemodynamic measurements. We conclude that
      Doppler echocardiography accurately assesses left heart hemodynamics in
      critically ill patients. Since this technique can be readily acquired, it can be
      ideal for the rapid assessment of hemodynamic parameters in critically ill
      patients, especially when right heart catheterization is delayed or is
      problematic.

PMID- 7639167
TI  - Impact of a thrombolysis research trial on time to treatment for acute myocardial
      infarction in the emergency department.
AB  - Because time to treatment in AMI is a critical factor in long-term outcome, it is
      important that complex trials designed to improve reperfusion therapy do not
      delay the time to treatment. Participation in the TIMI 5 trial did not
      significantly prolong our door-to-needle time. These results indicate that, if
      done carefully, complex, labor-intensive studies can be performed within a
      reasonable time limit. Care should be taken to design protocols incorporating
      easy drug preparation, informed consent by the ED, and efficiency of trial
      initiation.

PMID- 7639168
TI  - Electrophysiologic effects of intranasal cocaine.

PMID- 7639169
TI  - Randomized comparison of atenolol and fludrocortisone acetate in the treatment of
      pediatric neurally mediated syncope.
AB  - Overall, these results indicate that oral treatment of neurally mediated syncope
      is safe and efficacious. Further randomized trials in children will be required
      to determine the significance of a placebo effect, as well as potential
      differences in results related to the mechanism of syncope.

PMID- 7639170
TI  - Relation of left ventricular chamber shape in patients with low (< or = 40%)
      ejection fraction to severity of functional mitral regurgitation.

PMID- 7639171
TI  - Mitral valvotomy with the Inoue balloon in juvenile rheumatic mitral stenosis.
AB  - We conclude that balloon valvotomy of the mitral valve with the Inoue technique
      is a safe and effective procedure for treating juvenile rheumatic MS. The almost
      complete absence of iatrogenic atrial septal defect and the low incidence of
      significant mitral regurgitation is noteworthy.

PMID- 7639172
TI  - Percutaneous transvenous mitral commissurotomy for mitral stenosis patients with
      markedly severe mitral valve deformity: immediate results and long-term clinical
      outcome.
AB  - In conclusion, to evaluate the efficacy and safety of PTMC for mitral stenosis
      patients with markedly severe valve deformity, we performed PTMC in 17 patients
      with severe mitral stenosis assessed by echocardiography (echo score > or = 12).
      This study demonstrates that PTMC can be performed safely and is clinically
      useful in treating the mitral stenosis patient with a markedly severe valve
      deformity.

PMID- 7639173
TI  - Clinical significance of high-frequency, low-amplitude electrocardiographic
      signals and QT dispersion in patients operated on for tetralogy of Fallot.

PMID- 7639174
TI  - Automated determination of pulmonary artery pulsatility during transesophageal
      echocardiography.

PMID- 7639175
TI  - Quantitative measurement of normal and excessive (cor adiposum) subepicardial
      adipose tissue, its clinical significance, and its effect on electrocardiographic
      QRS voltage.
AB  - In summary, adipose tissue in the heart may constitute up to 50% of the cardiac
      weight. The greater amounts of cardiac adipose tissue are associated with lower
      total 12-lead QRS voltages.

PMID- 7639176
TI  - Tuberous sclerosis and cardiac rhabdomyoma.
AB  - We conclude that echocardiographically detected cardiac rhabdomyomata are common
      in patients with tuberous sclerosis complex, and are more prevalent and prominent
      in the younger patient. Tumors regress in size or number, or both, in most
      patients aged < 4 years, and less so in older patients. Cardiac rhabdomyomata are
      associated with a higher incidence of preexcitation and may increase the risk for
      arrhythmia.

PMID- 7639177
TI  - Spontaneous closure of a patent foramen ovale and disappearance of impending
      paradoxical embolism after fibrinolytic therapy in the course of massive
      pulmonary embolism.
AB  - Our case suggests that a negative transesophageal contrast echocardiographic
      study during stable hemodynamic conditions does not definitively rule out the
      possibility of a functional PFO with transient right-to-left shunting in
      situations of increased right heart pressures. In addition, we confirm that
      thrombolysis can be considered as an alternative to surgery in high-risk patients
      with impending paradoxical embolism. The risk-to-benefit ratio of this choice,
      however, should be individually evaluated.

PMID- 7639178
TI  - Left ventricular and papillary muscle rupture following blunt chest trauma.

PMID- 7639179
TI  - Personal finances.

PMID- 7639180
TI  - Comments on Thomas J. Moore's article "Justice delayed--the Dean Mason story.

PMID- 7639181
TI  - Coronary angiography in Q-wave versus non-Q-wave acute myocardial infarction.

PMID- 7639182
TI  - False-positive diagnoses in exfoliative cytology.

PMID- 7639183
TI  - Cocaethylene. What is it?

PMID- 7639184
TI  - Laboratory medicine parameter. Utilizing monospecific antihuman globulin to test
      blood-group compatibility.
AB  - When using polyspecific antihuman globulin (AHG) reagents to detect unexpected
      antibodies or for crossmatching, reactivity in the AHG phase may be due
      exclusively to the AHG anticomplement component. A lengthy evaluation may be
      needed to prove that the reactivity is caused by a "nuisance" antibody, one that
      is clinically insignificant. Clinically significant transfusion intolerance is
      rare when caused by blood group alloantibodies, which are detected only with AHG
      sera that contain anticomplement activity. Using monospecific anti-IgG AHG
      reagents to detect unexpected antibodies offers reliability while avoiding
      interference from some common and clinically insignificant IgM complement-fixing
      antibodies, and thereby saves time and expense.

PMID- 7639185
TI  - Surgical pathology examination of lymph nodes. Practice survey by American
      Society of Clinical Pathologists.
AB  - The American Society of Clinical Pathologists surveyed 363 pathologists to
      determine practices used in processing and reporting lymph node specimens
      submitted for surgical pathology examination. This topic is of interest because
      lymph nodes are some of the more common organs biopsied for diagnostic purposes
      and the constant change in and diversity of classification systems in the past 30
      years. The definition of newly recognized entities and the use of sophisticated
      diagnostic tools also have made it difficult for there to be a solid consensus of
      pathologists in diagnosing lymphoproliferative disorders for correlation with
      clinical behavior and response to therapy. The survey, conducted in November
      1992, contained 79 questions. Participants were selected to represent a variety
      of practice settings and 179 (49%) responses were received.

PMID- 7639186
TI  - False-positive interpretations of carcinoma in exfoliative respiratory cytology.
      Report of two cases and a review of underlying disorders.
AB  - The false-positive interpretation of malignancy is a potential pitfall of
      exfoliative respiratory tract cytopathology. However, the underlying causes of
      this problem are still relatively under-recognized. The authors herein present
      two additional examples in which bronchial brushing and washing specimens were
      misinterpreted as showing carcinoma of the lung. The first case concerned a
      patient with a granulomatous mass that simulated a malignancy on chest
      radiographs and was the apparent cause of atypical bronchial squamous metaplasia
      (ABSM). Exfoliated cells from the latter process were thought to explain the
      false-positive cytologic result in that instance. In the second case, a large
      cell angiocentric T-cell lymphoma replaced the lower lobe of the left lung. It
      was likewise associated with ABSM as the cause of a mistaken diagnosis of
      carcinoma in exfoliative respiratory cytology specimens, representing the first
      instance of such an association of which the authors are aware. Repeated
      evaluation of all bronchial cytology samples by several experienced pathologists
      yielded no reliable observations that might have been used to avoid an erroneous
      interpretation in either case. A review is provided of the spectrum of underlying
      conditions that may be associated with false-positive respiratory cytology
      results.

PMID- 7639187
TI  - Interphase cytogenetics of renal cortical neoplasms. Correlation with DNA ploidy
      by flow cytometry.
AB  - The genotypic changes in 22 renal cortical neoplasms and 16 of the corresponding
      normal kidney tissues by fluorescence in situ hybridization (FISH) were studied
      using directly labelled probes for chromosomes 7, 8, 10, 11, 12, 17, 18, X, and
      Y, and by flow cytometry (FCM). DNA ploidy analysis revealed 8 DNA aneuploid and
      14 DNA diploid neoplasms. The mean single spot hybridization in normal kidney was
      5 +/- 0.9% for chromosomes 7, 8, 10, 11, 12, and the X in females. The mean
      single spot hybridization for chromosomes 17 and 18 was 14.9% and 18.5%,
      respectively. The mean number of more than two (> 2) hybridization signals in
      normal kidney cells for all autosomes and the X-chromosome in females was 3 +/-
      1.2%. Significant chromosomal loss was restricted to chromosomes 8, 18, X, and Y.
      The net chromosomal gain and loss correlated with the DIs in aneuploid tumors.
      All DNA diploid neoplasms showed both chromosomal loss and gain with a tendency
      to a net loss. No apparent correlation between the chromosomal aberrations and
      the clinicopathologic factors was found in this cohort. Our study demonstrates
      that: (1) tissue specific controls may provide better information for definable
      performance criteria for this technique; (2) monosomy can more reliably be
      assessed on fresh samples; (3) chromosomal loss is confined to certain
      chromosomes; (4) DNA diploid tumors manifest heterogeneous gain and loss of
      various chromosomes with a tendency to a net loss; and (5) integrated FISH and
      FCM analysis provide more information on the chromosomal abnormalities of these
      neoplasms.

PMID- 7639188
TI  - ThinPrep versus conventional smear cytologic preparations in the analysis of
      thyroid fine-needle aspiration specimens.
AB  - Paired fine-needle aspiration specimens were analyzed from 41 surgically resected
      thyroid nodules, to compare diagnostic accuracy, amount (absent, mild, moderate,
      or marked) and pattern (diffuse, droplets, or both) of colloid, nuclear detail
      (poor, satisfactory, or excellent) and cytoplasmic detail (intact or disrupted)
      in ThinPrep (TP) (Cytyc, Marlborough, MA) versus conventional smear (CS)
      cytologic preparations. The 41 surgical specimens included 25 colloid nodules, 6
      papillary carcinomas, 4 follicular adenomas, 2 minimally invasive (encapsulated)
      follicular carcinomas, 3 Hashimoto's thyroiditis, and 1 Grave's disease. Both
      techniques identified seven of the eight carcinomas with the minimally invasive
      follicular carcinomas categorized as hypercellular follicular nodule, possibly
      malignant (HCFN). One papillary carcinoma was classified as a HCFN by both TP and
      CS techniques. The four follicular adenomas were classified as HCFN based on the
      TP slides. One oxyphilic follicular adenoma, associated with focal lymphocytic
      thyroiditis, was misinterpreted as Hashimoto's thyroiditis on a conventional
      smear. Three colloid nodules were interpreted as HCFN based on the TP slides. Two
      of these were similarly classified based on the conventional smear. ThinPrep
      slides contained less colloid and the colloid occurred as droplets rather than a
      diffuse pattern. TP slides had better nuclear detail but more often disrupted
      cytoplasm. In conclusion, the TP process does alter some cellular features;
      however, we experienced similar diagnostic accuracy with the TP and conventional
      smear preparations.

PMID- 7639189
TI  - Assessment of Ki-67 antigen immunostaining in squamous intraepithelial lesions of
      the uterine cervix. Correlation with the histologic grade and human
      papillomavirus type.
AB  - A formalin-fixation and paraffin-processing resistant epitope of Ki-67 cell
      proliferation-associated antigen was immunohistochemically detected by the MIB-1
      monoclonal antibody (Immunotech, Marseille, France) in 25 routinely processed
      cervical biopsies showing normal squamous epithelium or squamous metaplasia and
      in 65 cervical intraepithelial lesions (SILs) (44 low grade and 21 high grade
      SILs) with human papillomavirus (HPV) infection. Expression of Ki-67 antigen was
      exclusively confined to the parabasal and basal layers of normal and metaplastic
      epithelium. There was no significant difference of Ki-67 antigen immunostaining
      between normal cervical biopsies and cases of squamous metaplasia. In SIL
      specimens, the staining was markedly increased in the parabasal and basal layers
      and Ki-67-positive cells were also distributed in the intermediate (low grade
      SIL) or all layers of epithelium (high grade SIL). Statistically significant
      differences for the density of Ki-67 antigen-labeled cells, which were assessed
      with an image analysis system, were found in comparisons between normal or
      metaplastic epithelium and SILs (P < .001) and between low grade SILs and high
      grade SILs (P < .001). In our series of SILs, HPV 16/18 and 31/33/35/novel types,
      which were found in both low grade and high grade SILs, were significantly
      associated with higher densities of Ki-67 antigen-positive cells than HPV 6/11
      types that were found exclusively in low grade SILs. There was no significant
      difference found between the densities of Ki-67 antigen-labeled cells in HPV
      16/18-positive and HPV 31/33/35/novel types-positive tissues in our series of
      SILs taken as a whole or when segregating SILs into low grade and high grade.

PMID- 7639190
TI  - Adrenocortical cytopathology.
AB  - Cytopathologic smears and/or imprints of human adrenal cortex (9 cases) and its
      disorders were examined, including adrenocortical nodule (3 cases),
      adrenocortical adenoma (23 cases), carcinoma (8 cases), and renal cell carcinoma
      (6 cases). Immunocytochemistry directed against 3 beta-hydroxysteroid
      dehydrogenase and adrenal-4-binding protein (Ad4BP), a transcription factor in
      steroidogenesis, was also performed. There were no cytologic differences between
      normal adrenal and adrenocortical nodules. Large nuclei with prominent nucleoli
      were observed predominantly in adrenocortical neoplasms. Cellular atypia or
      pleomorphism and the degree of cohesiveness were unreliable criteria in
      differentiating between adrenocortical adenoma and carcinoma. Mitosis and
      necrotic materials were observed only in adrenocortical carcinoma. These
      cytologic findings were considered contributory, but not diagnostic when
      evaluating adrenocortical disorders because of marked intra-tumoral
      heterogeneity. There were no reliable cytologic criteria in differentiating
      adrenocortical and renal cell carcinoma. Immunocytochemistry of 3 beta
      hydroxysteroid dehydrogenase and especially Ad4BP was demonstrated to aid greatly
      in the differential diagnosis between these carcinomas by identifying
      adrenocortical parenchymal cells.

PMID- 7639191
TI  - Quality control of imprint and tissue section DNA ploidy analysis in image
      analysis systems utilizing cell culture-based control materials.
AB  - Currently, there are no standard controls available for quality control of DNA
      ploidy assays in image analysis systems. The authors have developed a system of
      controls based on cultured human cell lines that can mimic tissue sections and
      touch preparations. This allows for quality control for the entire process for
      DNA ploidy analysis from the initial cutting of the paraffin block or production
      of the touch preparation through fixation, staining, and interactive image
      analysis. The use of cell line controls rather than normal tissue is advantageous
      because of cell population homogeneity and the volume of uniform slides that are
      obtainable. This system, while providing an excellent means of controlling day-to
      day performance of DNA ploidy analysis, may also be adapted for use as a means of
      multi-institutional proficiency testing.

PMID- 7639192
TI  - Fatty acids. Biochemistry to clinical significance.
AB  - Fatty acids are a major source of lipids in the diet. Dietary fatty acids are
      able to significantly influence the concentration of serum cholesterol and
      thereby influence the risk of atherosclerosis. This brief review on fatty acids
      will present information on the structure and nomenclature of fatty acids, the
      metabolic pathways for fatty acids in cells, and the influence of dietary fatty
      acids on serum cholesterol levels.

PMID- 7639193
TI  - Cocaine and cocaethylene binding in human serum.
AB  - The binding of cocaine (COC) and cocaethylene (CE) in human serum was studied by
      equilibrium dialysis. Scatchard analysis suggested a high-affinity binder (Ka,
      2.56 x 10(4)L/mol; Bo, 7.38 x 10(-5) mol/L) and a low-affinity binder (Ka, 4.47 x
      10(3)L/mol; Bo, 2.77 x 10(-4) mol/L) for COC. Two high-affinity binders (Ka, 5.21
      x 10(4) L/mol; Bo, 2.54 x 10(-5) mol/L; and Ka, 4.32 x 10(4) L/mol; Bo, 2.43 x
      10(-5) mol/L) were discernible for CE. For both compounds additional, very-low
      affinity, high-capacity (nonspecific) binding was also seen. Supplementation of
      serum with specific proteins suggested that the high-affinity binding was due to
      alpha-1-acid glycoprotein, whereas the low-affinity binding was due to albumin,
      inasmuch as such supplementation increased the ratio of bound to free drug for
      both COC and CE.

PMID- 7639194
TI  - Confirmation and quantitation of cocaine, benzoylecgonine, ecgonine methyl ester,
      and cocaethylene by gas chromatography/mass spectrometry. Use of microwave
      irradiation for rapid preparation of trimethylsilyl and T-butyldimethylsilyl
      derivatives.
AB  - The authors developed a technique by which cocaine metabolites as well as
      cocaethylene can be identified and quantitated using gas chromatography/mass
      spectrometry (GC/MS), and deuterated standards of benzoylecgonine, cocaine,
      ecgonine methyl ester, and cocaethylene as internal standards. The authors used a
      solid phase extraction (Clean Screen, Worldwide Monitoring Corporation, (Horsham,
      PA)) technique, and rapid derivatization of metabolites using microwave
      irradiation before GC/MS analysis. The t-butyldimethylsilyl derivatives (prepared
      by microwave irradiation in 2.5 minutes, 640 Watts [W]) offered better baseline
      separation and chromatography than conventional trimethylsilyl derivatives. The
      assay was linear between 0.87-17.3 mumol/L of benzoylecgonine (250-5,000 ng/mL)
      concentration, 0.83-16.6 mumol/L of cocaine (250-5,000 ng/mL), 0.79-15.8 mumol/L
      of cocaethylene (250-5,000 ng/mL) and 1.25-25.1 mumol/L of ecgonine methyl ester
      (250-5,000 ng/mL). The yields are comparable between the microwave technique and
      conventional heating.

PMID- 7639195
TI  - alpha-Glutathione S-transferase as a marker of hepatocellular damage in chronic
      hepatitis C virus infection.
AB  - alpha-Glutathione S-transferase (alpha GST) may be a good serologic marker of
      hepatocellular damage because of its low molecular weight, uniform hepatic
      distribution, high cytosolic concentration, and short half-life. To determine the
      clinical utility of alpha GST in patients with chronic hepatitis C virus (HCV)
      infection, serum alpha GST levels were measured in 96 patients with chronic HCV
      infection, of whom 47 subsequently underwent interferon-alpha therapy. Patients
      were simultaneously evaluated with conventional liver biochemistry, serum HCV RNA
      levels, and liver histology. Different methods of serum collection did not affect
      alpha GST values, indicating that this was a stable serum marker. In 93% of
      patients with chronic HCV infection, alpha GST was elevated and showed an
      excellent correlation with serum aminotransferases. Histologic analysis revealed
      a correlation of alpha GST with both lobular inflammation and bile duct lesions.
      There was no correlation between serum alpha GST levels and the demographic
      features, mode of transmission, virologic, other histologic parameters, or
      subsequent response to interferon-alpha. During serial monitoring in patients
      undergoing interferon-alpha therapy, elevation of serum alpha GST correlated with
      biochemical relapse and in some patients virologic relapse in the presence of
      normal liver biochemistry. alpha GST was persistently elevated in all
      nonresponders. Four of six of those patients who responded completely followed by
      early relapse had elevated alpha GST intermittently or continuously during
      therapy despite normalization of serum aminotransferases. Two of five of those
      with a complete and sustained response had elevated alpha GST during treatment
      and follow-up, and both were also seropositive for HCV RNA during follow-up.
      These data demonstrate that alpha GST is a stable marker, has similar diagnostic
      utility as serum aminotransferases, and may have a role in the monitoring of
      patients undergoing interferon-alpha therapy.

PMID- 7639196
TI  - Trisomy 12 in Richter's transformation of chronic lymphocytic leukemia.
AB  - Conventional cytogenetic data and fluorescence in situ hybridization (FISH)
      interphase cytogenetic studies have shown that trisomy 12 is found in many cases
      of B-cell chronic lymphocytic leukemia (B-CLL). Several reports indicate that +12
      is an acquired numerical cytogenetic abnormality, and may be associated with a
      worse prognosis or more extensive disease. Wright-Giemsa-stained blood or bone
      marrow smears obtained after initial diagnosis, and subsequent lymph node cells,
      bone marrow aspirate smears, or effusions were retrospectively studied from five
      patients whose disease underwent morphologic transformation from typical B-CLL to
      a high grade lymphoproliferative disease (Richter's syndrome). Using an alpha
      satellite DNA probe to the centromere of chromosome 12, trisomy 12 was found in a
      proportion of cells from all five specimens with high grade lymphoproliferative
      disease, but in only one of five samples collected before transformation. These
      data suggest that +12 is an acquired cytogenetic abnormality in CLL and has a
      high frequency in Richter's syndrome. Because only a subpopulation of the
      neoplastic cells contain an extra copy of chromosome 12, it is unlikely that this
      numerical abnormality plays a direct role in transformation to high grade
      lymphoproliferative disease.

PMID- 7639197
TI  - Natural killer cell acute leukemia with myeloid antigen expression. A previously
      undescribed form of acute leukemia.
AB  - An acute leukemia of natural killer cell origin with myeloid antigen expression
      has not previously been described in the literature. Although lymphoproliferative
      disorders of large granular lymphocytes may be of natural killer cell origin and
      may have an aggressive clinical course, the morphology in the blood and bone
      marrow is that of large granular lymphocytes. An acute leukemia with blastic
      morphology is described, which was of natural killer cell origin by flow
      cytometric immunophenotyping (CD45+, CD2+, CD3, CD7+, CD5+, CD4, CD8, CD56+,
      CD57, CD16, CD13+, CD33+, CD34+, C-Kit+, HLA-DR, TdT) and histochemical staining.
      This was supported by the lack of T-cell gene rearrangement. The patient had an
      aggressive clinical course despite therapy for acute lymphoblastic leukemia. The
      authors recommend routine flow cytometric immunophenotyping of acute leukemia to
      identify other similar cases to better clinically define this entity.

PMID- 7639198
TI  - On the biological role of T-lymphocytes in T-cell-rich B-cell lymphomas.

PMID- 7639199
TI  - Granulomatous orchitis associated with retrograde ejaculation.

PMID- 7639200
TI  - Adolescent problem behavior: the effect of peers and the moderating role of
      father absence and the mother-child relationship.
AB  - Examined the effect of peer problem behavior, the absence of a father or
      equivalent in the home, and the mother-adolescent relationship as predictors of
      adolescent problem behavior in a sample of 112 African American adolescents.
      Statistical analyses compared a moderator model to a mediational model and a
      cumulative risk model. As predicted, the moderator model was superior to the
      alternative models. Specifically, whereas the mediational model predicted that
      the effect of father absence and the mother-child relationship upon adolescent
      problem behavior would be mediated by peer problem behavior, neither effected
      peer problem behavior or adolescent problem behavior. Similarly, a cumulative
      risk index did not predict either child or parent reports of problem behavior and
      was not sensitive to specific contingencies that existed between the predictor
      variables. In contrast, an interactive, moderator model described the data quite
      well. This model suggested that father or equivalent absence magnifies the
      negative impact of peer problem behavior, while a positive mother-adolescent
      relationship attenuates this risk. A strong mother-adolescent relationship also
      served to protect adolescents in father-absent homes from the risk of peer
      problem behavior.

PMID- 7639201
TI  - Depression and unemployment: panel findings from the Epidemiologic Catchment Area
      study.
AB  - Studies that have found an association between unemployment and psychological
      depression often fail to establish the direction of causal influence. Analyses of
      Epidemiologic Catchment Area panel data revealed that of employed respondents not
      diagnosed with major depression at first interview, those who became unemployed
      had over twice the risk of increased depressive symptoms and of becoming
      clinically depressed as those who continued employed. Although the increase in
      symptoms was statistically significant, the effect on clinical depression was
      not, possibly because of the low power of the test. The reverse causal path from
      clinical depression at Time 1 to becoming unemployed by Time 2 was not supported.
      The unemployment rate in the respondent's community at time of interview was not
      related directly to psychological depression but appeared associated indirectly
      with depression via its impact on the risk of becoming unemployed. Implications
      for policy and further research were discussed.

PMID- 7639202
TI  - An examination of the cross-ethnic equivalence of measures of negative life
      events and mental health among Hispanic and Anglo-American children.
AB  - Recently there has been concern over the need for mental health research within
      ethnic minority populations, particularly Hispanic populations. Although there
      has been research focusing upon the similarity of mental health problems among
      Hispanic and Anglo-American samples, the absence of information regarding the
      cross-ethnic measurement equivalence of the assessment tools used in these
      comparisons seriously limits the interpretability of these findings. The two
      reported studies were designed to (a) examine the cross-ethnic functional and
      scalar equivalence of several mental health measures by examining the
      interrelations of these mental health indicators and examining the regression
      equations using negative life events to predict mental health outcomes; and (b)
      compare several mental health indicators among Hispanic and Anglo-American 8- to
      14-year-old children. Findings suggest considerable cross-ethnic functional and
      scalar equivalence for the measure of depression, conduct disorders, and negative
      life events. In addition, findings indicate that the Hispanic children scored
      higher in depression than did the Anglo-American children, but this difference
      could be a function of differences in SES. The reader is cautioned that the
      present samples included only English-speaking and primarily Mexican American
      children.

PMID- 7639203
TI  - Relationship between drug preference and indicators of psychiatric impairment.
AB  - This study was conducted to investigate the relationship between the indicators
      of psychiatric disorders of individuals and their choice of either cocaine or
      heroin, drugs that differ markedly in their pharmacological effects. Cocaine acts
      as an intense stimulant, and heroin has profound sedative effects. This
      investigation examined the relationship between preference for heroin or cocaine
      and indicators of psychiatric impairment. Data from 282 subjects were grouped
      according to drug of choice and analyzed. Ninety-three percent of these subjects
      were African-American, 32% were female, and the average age was 34. Univariate
      and multivariate statistical analyses, such as discriminant analyses, were used
      to determine group differences. The results are evaluated and interpreted in
      relation to both the current empirical findings and to the hypotheses and
      theories postulated as a result of earlier clinical observations on drug of
      choice and psychopathology. Discriminant analysis yielded an overall correct
      classification rate of 75%. The discriminant function suggests that members in
      the cocaine drug of choice group as contrasted with members in the heroin
      preference group can be characterized as more socially inhibited and more self
      defeating after adjusting for differences in age, duration of use of illicit
      substances, and marital status. Those who favored cocaine as contrasted with
      those who favored heroin were more likely to have never married, be younger, and
      have used illicit substances for a shorter period of time.

PMID- 7639204
TI  - Diagnosing comorbidity in substance abusers: a comparison of the test-retest
      reliability of two interviews.
AB  - This study examines the test-retest reliability of two interview schedules
      (computer- and clinician-administered) in diagnosing lifetime comorbidity in
      treated substance abusers. The Computerized Diagnostic Interview Schedule (C-DIS)
      and the Structured Clinical Interview for DSM-III-R (SCID) were both administered
      to 173 substance abusers after random assignment to one of two groups. Within 1
      to 2 weeks, subjects in the first group repeated the C-DIS and subjects in the
      second group were reinterviewed by a different clinician, blind to the results of
      the initial SCID. Both instruments showed good to excellent reliability for DSM
      III-R psychoactive substance use disorders with kappas ranging from .50 to .89
      for individual disorders. However, the reliability of comorbid other mental
      disorders was substantially poorer on both instruments, particularly the SCID. C
      DIS kappas ranged from -.05 for generalized anxiety to .70 for simple phobia.
      SCID kappas ranged from .31 for panic disorder to .83 for antisocial personality
      disorder. Anxiety disorders as a category, some phobic disorders, and antisocial
      personality disorder showed acceptable levels of test-retest reliability on both
      instruments. There was a trend for borderline or threshold cases to account for
      some of the disagreement on the C-DIS. Differences of opinion between clinicians
      on organicity accounted for some of the disagreements on panic disorder and major
      depression. The C-DIS, unlike the SCID, tended to diagnose more disorders at
      initial interview, perhaps a result of its tedious probe structure. Neither
      instrument should be administered only once to provide a reliable lifetime
      diagnostic profile of comorbidity in substance abusers.

PMID- 7639205
TI  - Predictive validity of the Drug Lifestyle Screening Interview: a two-year follow
      up.
AB  - One hundred and eighteen inmates enrolled in a comprehensive residential drug
      treatment program were administered the Drug Lifestyle Screening Interview (DLSI)
      and followed for 2 years. A marginally significant predictive effect was observed
      in which subjects achieving elevated DLSI scores (> or = 12) displayed more
      subsequent alcohol and drug misuse than lower scoring subjects, 21.7 versus 9.7%.
      The Lifestyle Criminality Screening Form (LCSF) enjoyed a somewhat stronger
      predictive relationship with future outcome in that 27.3% of the high scoring
      subjects (LCSF score > or = 10) subsequently misused alcohol or other drugs as
      opposed to only 4.4% of the low scoring subjects. Regression analysis also
      revealed the superiority of the LCSF in predicting future outcome. These findings
      suggest that criminal background should be taken into account when evaluating the
      relapse potential of drug-involved offenders once they leave treatment.

PMID- 7639206
TI  - Aggressivity among sons of substance-abusing fathers: association with
      psychiatric disorder in the father and son, paternal personality, pubertal
      development, and socioeconomic status.
AB  - An association between childhood aggression and risk for subsequent development
      of a substance abuse disorder is now well-accepted. In order to better understand
      the relationship between the presence of paternal substance abuse and aggression
      among their offspring, 10-12 year old sons of fathers with (n = 34) and without
      (n = 39) a history of a substance abuse disorder were contrasted on demographics,
      aggressivity, biological indices of reproductive maturation, and the presence of
      psychiatric diagnoses. In addition, personality factors, the potential for
      physical abuse, and psychiatric diagnoses were also ascertained among their
      fathers. Sons of substance-abusing fathers were found to be significantly more
      aggressive than sons of nonsubstance abusers. However, they also differed from
      comparison boys on the basis of SES and school grade attained, as well as the
      proportion with specific psychiatric disorders. Substance-abusing fathers
      differed from nonsubstance-abusing men in terms of personality factors and the
      presence of specific psychiatric disorders, including antisocial personality.
      They also showed significantly higher child abuse potential scores. A multiple
      regression analysis of factors contributing to aggression in the boys revealed
      that a paternal personality factor characterized by stress reactivity,
      alienation, and aggression was the most robust contributor to aggression among
      the boys. The boys' diagnoses of attention deficit disorder, oppositional defiant
      disorder, and lower household socioeconomic status were also significant
      predictors of aggressivity. Contrary to expectations, paternal, psychiatric
      diagnoses, substance abuse status, and potential for physical abuse were
      noncontributory. The results suggest potential mechanisms by which both
      aggression and risk for substance abuse may be transmitted from father to son.

PMID- 7639207
TI  - Reliability of two brief questionnaires for drug abuse treatment evaluation.
AB  - The authors report the inter-interviewer reliability of two brief questionnaires
      developed to measure the effects of innovations in methadone maintenance. The
      instruments were designed to answer the research questions, but to intrude only
      minimally into the clinical assessment and treatment processes. The Initial
      Interview, completed at the time of admission, yielded information on 23
      variables, and the Followup Interview, completed as soon as possible after the
      first anniversary of admission, yielded information on 20 variables. To assess
      reliability, a repeat interview was conducted by a different interviewer
      immediately after the first interview was completed. Repeat interviews were
      conducted with 19 subjects who completed the Initial Interview and 30 who
      completed the Followup Interview. Exact agreement was found in all the pairs of
      responses from the Initial Interview for 5 of the 6 categorical variables and 6
      of the 17 quantitative variables. For the remaining 11 quantitative variables,
      the intraclass correlation coefficients ranged from .700 to .999. Exact agreement
      was found in all pairs of responses from the Followup Interview for 2 of the 4
      categorical variables and 8 of the 16 quantitative variables. For each of the
      remaining categorical variables, the kappa statistic was significant (.73 and
      .49). For the remaining 8 quantitative variables, the intraclass correlation
      coefficients ranged from .750 to .999. The findings signify satisfactory
      interviewer reliability of the instruments. These brief instruments could easily
      be adapted for use in other treatment evaluation studies where brevity in data
      collection is considered desirable.

PMID- 7639208
TI  - Patterns of cocaine use among individuals in substance abuse treatment.
AB  - Recognition of the heterogeneity among substance abusers has led to increased
      attention to the issue of client-treatment matching. One approach involves
      identifying different patterns of use within samples of substance abusers. The
      present preliminary report employed a cluster analysis of various aspects of
      cocaine use to examine subgroups of cocaine users within a sample of individuals
      in treatment for substance abuse. Three clusters emerged, differentiated
      primarily by quantity/frequency of use and route of administration. The resulting
      subgroups were compared on measures of external validity. Results suggest that
      subgroups of cocaine use patterns do exist within a sample of substance abusers.
      In addition, these subgroups differ in age of cocaine use onset and the severity
      of negative consequences. Future research is needed to establish the clinical
      utility of these clusters.

PMID- 7639209
TI  - Intensive surveillance for cocaine use in obstetric patients.
AB  - OBJECTIVE: To determine the value of intensive surveillance for cocaine use in
      pregnancy and also determine the prevalence of cocaine use in our institution.
      METHODS: Among 124 consecutive new obstetrical clinic patients, urine specimens
      were collected anonymously at the first prenatal visit, in each subsequent
      trimester of pregnancy, and on labor and delivery. Corresponding newborn urine
      and meconium were also collected for these patients. 324 urine specimens and 49
      meconium specimens were obtained. A local private group also collected first
      prenatal visit urine from an additional 104 patients. Urine specimens were
      analyzed for cocaine metabolites by fluorescent polarization immunoassay with
      confirmation of positive results by gas chromatography/mass spectrophotometry.
      RESULTS: One clinic patient had a positive cocaine screen. All other urine and
      meconium screens were negative. CONCLUSION: Intensive surveillance did not
      increase the detection rate for cocaine abuse in our obstetric population. We
      also found that the prevalence of cocaine abuse among obstetrical patients at our
      institution is low (< 1%). These data reconfirm that resource allocation for drug
      treatment centers should be based on prevalence data specific to an area or
      institution.

PMID- 7639210
TI  - Needle-using practices within the sex industry. National AIDS Research
      Consortium.
AB  - The addicted prostitute faces a risk of AIDS from both her sexual practices and
      intravenous drug use. While the sexual practices of these women have been
      studied, much less is known about their needle-using practices. We suggest women
      in the sex industry are more enmeshed in the drug-using scene and occupy a more
      constricted set of social roles than other women. They will therefore lack the
      resources and have fewer opportunities to engage in safer behaviors compared to
      women who support themselves by other means. The analysis is based on 9,055
      addicted women not in treatment. Women who trade sex for money and/or drugs are
      less likely to use new needles on any consistent basis or to clean old needles.
      They are more likely to share needles with others compared to women who support
      themselves by other means. Three identifiable patterns of needle-using practices
      emerge: indiscriminate sharing, monogamous sharing with a sexual partner, and
      exclusive use of new needles. To reach those engaged in promiscuous sharing,
      needle-swapping programs must be particularly "user friendly." Where needle-using
      behaviors reflect an intimate relationship, the spouse/sex partner must be
      engaged if change is to take place. Finally, policymakers and practitioners
      should capitalize on the strengths and strategies of those who report they
      consistently use sterile needles.

PMID- 7639211
TI  - Relationship between concurrent substance abuse in psychiatric patients and
      neuroleptic dosage.
AB  - The use of a structured diagnostic interview (The Schedule for Affective
      Disorders and Schizophrenia) with 58 consecutively admitted general adult
      psychiatric patients revealed that 62.1% of them abused alcohol and 58.6% had a
      substance use disorder. The drug abusers did not differ significantly from the
      nonabusers on mean psychoticism (Brief Psychiatric Rating Scale) scores. However,
      they received higher doses of antipsychotic agents (mean daily dose 1022 mg CPZ
      EQ (SD = 614) vs 609 mg CPZ EQ (SD = 481); z = 2.58, p < .01) to achieve
      stabilization. The clinical implications of this finding are discussed.

PMID- 7639212
TI  - Understanding gender differences in psychosocial functioning and treatment
      retention.
AB  - Although much research has compared males and females who seek substance abuse
      treatment, little attention has been given to factors that moderate or mediate
      relations between gender and dependent measures such as psychological functioning
      and retention. Consequently, this study examined whether family support, prior
      homelessness, embracement of the 12-step ideology, and attributions for addiction
      modified or accounted for these relations. Bivariate correlations showed that
      females reported less self-esteem and family support, as well as more self-blame
      and parental blame, than did their male counterparts. In contrast, males
      displayed more prior homelessness and less program completions than did the
      females. Multivariate analyses indicated that the relatively poor functioning of
      females was linked to lower family support and greater tendencies to blame
      themselves and their parents for their addictions. In addition, females were most
      likely to display low esteem when they engaged in high embracement of the 12-step
      ideology. On the other hand, the lower rate of program completion for males was
      linked to their higher rates of prior homelessness.

PMID- 7639213
TI  - T cell counts from "methadone" and "nonmethadone" groups.

PMID- 7639214
TI  - "Cure" of Helicobacter pylori and "cure" of peptic ulcer: do they mean the same
      thing?

PMID- 7639215
TI  - Achalasia: the debate continues.

PMID- 7639216
TI  - The validity and importance of subtypes in autoimmune hepatitis: a point of view.
AB  - OBJECTIVE: To advocate formal subclassification of autoimmune hepatitis into two
      types based on the presence of mutually exclusive immunoserological markers,
      target antigen diversity, contrasting genetic predispositions, and differences in
      clinical profile and behavior. METHODS: Relevant references in English were
      identified through a Medline Search (1984-1994) and through a personal library of
      journals and reprints. RESULTS: Antinuclear antibodies and/or smooth-muscle
      antibodies are mutually exclusive of antibodies to liver/kidney microsome type 1.
      The cytochrome monooxygenase P450 IID6 is the target autoantigen for patients
      with antibodies to liver/kidney microsome type 1, and patients with these
      autoantibodies are different from others. The human lymphocyte antigens DR3 and
      DR4 are risk factors for patients with antinuclear and/or smooth-muscle
      antibodies, whereas the B14, DR3, and C4A-QO antigens are common in patients with
      antibodies to liver/kidney microsome type 1. Patients with antibodies to
      liver/kidney type 1 are younger, and they more commonly have concurrent organ
      specific autoantibodies and/or immunological diseases than counterparts with
      antinuclear and/or smooth-muscle antibodies. They also progress to cirrhosis more
      frequently. CONCLUSIONS: Two distinct types of autoimmune hepatitis can be
      defined by immunoserological markers, genetic predispositions, autoantigen
      status, and clinical features. Each should be recognized as a valid and
      independent entity.

PMID- 7639217
TI  - Wrap session: is the Nissen slipping? Can medical treatment replace surgery for
      severe gastroesophageal reflux disease in children?
AB  - For over 20 yr, antireflux surgery has been the treatment of choice for severe
      gastroesophageal (GE) reflux disease in children, and antireflux operations are
      said to be the commonest major surgical procedures performed by pediatric
      surgeons in North America. Yet, only recently have the results of surgery been
      more closely examined; both the surgical morbidity and operative failure rates
      have been found to be particularly high in children with neurological impairment,
      repaired esophageal atresia, and chronic lung disease. Of interest, these groups
      of children are among those most at risk for developing severe GE reflux disease
      in the first place. Close examination of surgical reports also raises some
      questions about the indications for surgery in some children, specifically
      whether the presence of severe GE reflux disease had been established before
      surgery and whether a trial of appropriate medical management had been given.
      Failure of medical management has always been an accepted indication for surgery.
      However, in the past the medical management that was available for children was
      ineffective because drug dosages were not optimized (H2-receptor antagonists),
      the drugs had side effects precluding their use long term or in high doses
      (bethanechol, metoclopramide), or they were simply insufficiently potent to treat
      severe GE reflux disease (all the above drugs plus cisapride). Thus, in the past,
      failure of medical management did not mean failure of very much. In contrast, the
      proton pump inhibitor omeprazole has recently been shown to be effective and safe
      for the treatment of severe childhood GE reflux disease refractory to other
      medical treatments and where antireflux surgery has failed. The issues of why
      certain groups of children are at highest risk for severe GE reflux disease are
      discussed as are the outcomes and roles of surgical and medical treatment for all
      groups of children with severe GE reflux disease. The options of antireflux
      surgery or omeprazole should be reserved for those children with severe GE reflux
      disease, e.g., GE reflux accompanied by a complication.

PMID- 7639218
TI  - Recrudescence of Helicobacter pylori infection in patients with healed duodenal
      ulcer after treatment with different regimens.
AB  - OBJECTIVE: To determine the 12-month posttherapy recurrence (recrudescence) of
      Helicobacter pylori in patients with healed duodenal ulcer after apparent
      eradication of the organism with anti-H. pylori treatment. The influence of
      original anti-H. pylori treatment regimens on the recrudescence was also
      evaluated. METHODS: One hundred and ninety patients who had duodenal ulcer healed
      and H. pylori eradicated (as assessed by four routine techniques 4 wk after the
      end of anti-H. pylori therapy) with one of five regimens were studied. The five
      regimens were: 1) colloidal bismuth subcitrate (CBS) 120 mg; 2) CBS plus
      amoxicillin (500 mg); 3) CBS plus metronidazole (400 mg); 4) CBS plus
      metronidazole and amoxicillin; and 5) CBS plus metronidazole and tetracycline
      (500 mg). CBS was taken four times daily for 4 wk, and antibiotics were taken
      three times daily for the first week. The patients were re-endoscoped, and the
      status of H. pylori, duodenal ulcer, and gastritis was assessed after a period of
      follow-up (mean 14 months after commencement of treatment). RESULTS: H. pylori
      infection recurred in 36 (18.9%) of these patients. Recrudescence rate with
      monotherapy was 47.1%, with dual therapy 29.2-35% and with triple therapy 9.2
      14.3%. Nineteen (52.7%) of the 36 patients with recrudescent infection had ulcer
      relapse, and the rate for H. pylori-negative patients was 3.2% (5/154).
      CONCLUSION: Recrudescence of H. pylori infection after apparent eradication can
      occur, but it could be that the treatment was only suppressing the organism. The
      definition of eradication of H. pylori infection may need to be revised, and more
      sensitive techniques to assess eradication of H. pylori are required.

PMID- 7639219
TI  - Pneumatic dilation for achalasia without fluoroscopic guidance: safety and
      efficacy.
AB  - OBJECTIVES: To describe the technique of pneumatic dilation for achalasia without
      fluoroscopic guidance and to assess its safety and efficacy. METHODS: Twenty
      seven consecutive patients who underwent pneumatic dilation with the Rigiflex
      achalasia balloon under direct endoscopic visualization were reviewed. The
      balloon was passed into the stomach over a guidewire, withdrawn across the
      gastroesophageal junction, and dilated with the endoscope positioned proximally.
      Patients were graded pre- and posttreatment on the frequency of dysphagia,
      daytime regurgitation, nighttime symptoms, chest pain, and heartburn. Response
      was assessed by the improvement in dysphagia frequency. RESULTS: Twenty-seven
      patients (16 females, 11 males; mean age 54.0 yr) underwent 30 pneumatic
      dilations. The 30-mm balloon was used in most cases (67%). The mean postdilation
      follow-up was 21.1 months (1.5-57.4 months). The range of inflation pressures was
      8-18 psi (median 15 psi), and the duration of inflation was 30-120 s (median 90
      s). Eighteen of 27 patients (67%) had excellent or good results, six (22%) had
      fair results, and three (11%) had poor results. The outcome of pneumatic dilation
      was successful in 78% of patients after a single dilation and in 89% of patients
      overall. There were no perforations related to balloon inflation. CONCLUSIONS:
      The Rigiflex balloon can be successfully positioned across the gastroesophageal
      junction and dilated under direct endoscopic observation. Pneumatic dilation for
      achalasia can therefore be performed simply, safely, and effectively without the
      use of fluoroscopy.

PMID- 7639220
TI  - Screening for Barrett's esophagus by balloon cytology.
AB  - OBJECTIVE: to determine whether balloon cytology would allow a nonendoscopic
      diagnosis of Barrett's esophagus. METHODS: In 10 unselected patients with
      Barrett's esophagus, balloon cytology was performed with a Brandt esophageal
      cytology balloon catheter prior to endoscopy/esophageal biopsy. Specimens were
      cytologically evaluated for the presence of goblet cells and/or dysplasia.
      RESULTS: No patient had goblet cells or definitive columnar cell dysplasia.
      CONCLUSION: This technique with a commercially available balloon catheter does
      not allow for a nonendoscopic diagnosis of Barrett's esophagus.

PMID- 7639221
TI  - Sucralfate maintenance therapy in reflux esophagitis. Sucralfate Investigational
      Working Team.
AB  - OBJECTIVE: to prove in a double-blind placebo-controlled multinational trial the
      effects of sucralfate suspension 2 g BID and placebo in the prevention of
      recurrent reflux esophagitis. METHODS: One hundred and eighty-four patients from
      16 centers with reflux esophagitis Savary grade 1 and 2 were initially healed
      with antisecretory therapy before entering the study. They were randomly
      allocated to sucralfate suspension 2 g BID or placebo for 6 months. Symptoms were
      monitored monthly. Endoscopy was performed at the end of the trial or earlier in
      case of clinical suspension of relapse. RESULTS: The two treatment groups were
      well matched. We were able to analyze 88 sucralfate- and 93 placebo-treated
      patients. There was a significant reduction in the endoscopic relapse rate (31%
      in the sucralfate group vs. 65% in the placebo group, p < 0.001). This reduction
      was especially obvious for symptomatic relapses (10% vs. 34%, respectively, p <
      0.001). CONCLUSION: This is the first study to show that sucralfate suspension is
      capable of preventing recurrent reflux esophagitis in patients with solitary or
      confluent erosions previously healed with antisecretory therapy.

PMID- 7639222
TI  - Transjugular intrahepatic portosystemic shunt in nonliver transplant candidates:
      is it indicated?
AB  - BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) is an effective
      treatment of severe portal hypertension complications. Liver transplantation (LT)
      candidacy has not been a prerequisite to TIPS placement in some medical centers.
      OBJECTIVES: To investigate the outcome and survival of non-LT candidates after
      TIPS. METHODS: From November 1991 to February 1994, all patients referred for
      TIPS placement were evaluated for LT candidacy. Exclusions for LT included: age
      (> 70 yr), other significant medical conditions, or noncompliance. Indications
      for TIPS included refractory variceal bleeding during an acute bleed, recurrent
      bleeding after more than or equal to four sessions of sclerotherapy, or
      refractory ascites. RESULTS: Sixty patients received TIPS. Nineteen were
      considered non-LT candidates. Over a 2-yr follow-up, 14 of these non-LT
      candidates did not survive. Their median age was 63.5 compared with 56.5 yr for
      LT candidate nonsurvivors (p < 0.05). Among the 14 non-LT candidate nonsurvivors,
      10 were Childs C class, and eight had emergent TIPS placement. The 2-year
      mortality rate was 84% for non-LT candidates versus 24% for LT candidates. Median
      survival time for non-LT candidates was 2.6 months compared with 20 months in the
      LT candidates (p < 0.001). Only one death was due to a TIPS-related complication.
      CONCLUSIONS: TIPS is unquestionably an advancement in the management of patients
      with portal hypertension complications. Non-LT candidates, compared with LT
      candidates, tended to be older and of a Child-Pugh C class, and they had survival
      rates often less than 90 days post-TIPS. Given these high mortality rates, we
      need to address whether TIPS is indicated in these non-LT candidates.

PMID- 7639223
TI  - Extreme serum elevations of aspartate aminotransferase.
AB  - OBJECTIVE: To determine the frequency, etiology, and associated mortality of
      extreme elevations of serum AST. METHODS: The medical records were reviewed of
      all patients with a serum AST over 3000 U/L during 1 full calendar year at a
      large, tertiary-care hospital. Serum AST, with an upper limit of normal at 35
      U/L, is included in the automated, 18-test chemistry profile run on virtually all
      clinically ill patients admitted to this hospital. RESULTS: Of 23,125 admissions,
      56 patients had or developed serum AST concentrations greater than 3000 U/L, an
      occurrence rate of approximately two per 1000 admissions. Either liver or
      skeletal muscle was the origin of virtually all such AST elevations. Acute
      hypotension (ischemic or hypoxic hepatitis) accounted for the majority (29/56) of
      the cases; toxic (seven) or viral (four) hepatitis together accounted for 11/56
      cases. Overall mortality, on this admission, was 31/56 (55%). CONCLUSIONS:
      Extreme elevations of AST are most often attributable to hypoxic hepatitis.
      Patients with extreme AST due to hypoxic hepatitis had a 22/29 (75%) mortality
      compared with 9/27 (33%) for all other causes combined.

PMID- 7639224
TI  - A controlled study to determine the optimal dose regimen of interferon-alpha 2b
      in chronic hepatitis C.
AB  - OBJECTIVES: The efficacy of three different dose treatments of interferon (IFN)
      was evaluated in patients with chronic hepatitis C (HCV). METHODS: Ninety-one
      patients with chronic hepatitis C were allocated to receive 3, 6, or 10 U of
      recombinant IFN-alpha 2b three times weekly for 24 wk. The number of patients was
      26, 35, and 30 in the low, middle, and high dose groups, respectively. Treatment
      was discontinued, however, in four patients (one in the middle dose group and
      three in the high dose group) because of depression occurring 1-3 months after
      therapy began. A total of 87 patients, therefore, was analysed and was comprised
      of 26 patients in the low dose group, 34 in the middle dose group, and 27 in the
      high dose group. RESULTS: At the end of treatment, serum levels of ALT were
      normal in 50% (13/26) of patients in the low dose group, 70% (24/34) in the
      middle dose group, and 74% (20/27) in the high dose group. Patients with
      persistent normalization of ALT for 12 months of follow-up were defined as
      sustained responders. Twelve months after treatment cessation, the percentage of
      sustained responders was 23% (6/23) in the low dose group, 44% (15/34) in the
      middle dose group, and 41% (11/27) in the high dose group. Including the four
      patients who required discontinuation of IFN administration, the percentage of
      sustained responders was 43 and 37% in the middle and high dose groups,
      respectively. The clearance of HCV RNA was 40% in the middle dose group and 33%
      in the high dose group. This decrease in the clearance of HCV RNA was prominent
      in the high dose group. The percentage tended to be higher in the middle dose
      group, but the differences were not significant. CONCLUSIONS: The results suggest
      that a regimen of recombinant IFN-alpha 2b in a dose of 6 U three times weekly
      for 24 wk may be appropriate for the treatment of chronic HCV.

PMID- 7639225
TI  - Relationship of aminotransferases to liver histological status in chronic
      hepatitis C.
AB  - OBJECTIVES: Serum aminotransferase levels characteristically fluctuate in chronic
      hepatitis C, but their relationship to grade (i.e., inflammatory activity) and
      stage (i.e., degree of fibrosis) of liver disease is uncertain. We therefore
      correlated aminotransferase levels and liver biopsy findings in 90 patients with
      serologically confirmed chronic hepatitis C. METHODS: Mode of transmission;
      disease duration; symptoms and signs of liver disease; alcohol intake;
      autoantibody, HIV, and hepatitis B virus status; and liver biochemistries were
      obtained from records. Liver biopsies were 1) given a morphological diagnosis, 2)
      evaluated for features of chronic hepatitis C, and 3) scored with a histological
      activity index. RESULTS: Individual aminotransferase levels were not related to
      clinical or laboratory variables, nor were they reliably predictive of
      morphological diagnosis. No histological characteristics were associated with a
      particular range of aminotransferase values, except aminotransferases > 350 U/L,
      which were associated with piecemeal necrosis. Although mean values of
      aminotransferases were significantly lower among patients with chronic persistent
      hepatitis (CPH) (i.e., with minimal activity) compared with chronic active
      hepatitis (CAH) (mild to moderate activity) (ALT 110 U/L +/- 71 SD vs 256 +/-
      211; AST 57 U/L +/- 34 vs 123 +/- 88) and in the absence of piecemeal necrosis
      compared with in its presence (ALT 133 +/- 84 vs 207 +/- 149; AST 73 +/- 47 vs
      120 +/- 83), overlap of values was considerable between different histological
      groups. CONCLUSION: Aminotransferases do not predict liver histological status in
      chronic hepatitis C, although > or = 10-fold elevations suggest that piecemeal
      necrosis is present.

PMID- 7639226
TI  - Diagnostic laparoscopy: a 5-year experience in a hepatology training program.
AB  - Diagnostic laparoscopy continues to have a role in the evaluation and diagnosis
      of acute and chronic liver diseases, primary and metastatic liver tumors, and
      peritoneal diseases. We retrospectively reviewed the records of 1794 diagnostic
      laparoscopies performed at our institution from 1987 to 1992 to identify the
      indications, results, and safety of this procedure in our training program. A
      definitive diagnosis was made in 91% of cases with biopsy performed in 93%.
      Chronic liver disease was evaluated in 890 patients, and a diagnosis was made in
      98%. Four hundred thirty-seven patients were evaluated for suspected primary or
      metastatic carcinoma, and a diagnosis was made in 85%. Ascites was evaluated in
      73 patients, and a diagnosis was made in 82%. One-hundred sixty-four patients
      were evaluated for abnormal liver function tests, and a diagnosis was made in
      91%. HIV-related liver function test abnormalities were evaluated in 67 patients,
      and a diagnosis was made in 81%. One hundred sixty-three patients underwent
      diagnostic laparoscopy for the evaluation of hepatomegaly, splenomegaly,
      unexplained portal hypertension, fever of unknown origin, and cholestasis, and a
      diagnosis was made in 74% of cases. Eight major complications (including
      abdominal viscus perforation, hemobilia, splenic laceration, bleeding) and thirty
      one minor complications were seen. Our findings confirm that diagnostic
      laparoscopy is a safe and valuable procedure in the evaluation of chronic liver
      disease.

PMID- 7639227
TI  - Endoscopic retrograde cholangiopancreatography in pregnancy.
AB  - BACKGROUND: Pancreaticobiliary disease in pregnancy is relatively uncommon. The
      frequency of choledocholithiasis in pregnancy requiring intervention has been
      reported to be as low as one in 1200 deliveries. Traditionally, intervention in
      these patients has been surgical. Although surgery has an overall low morbidity
      and mortality for the expectant mother, it carries with it a 4- to 6-wk recovery
      period and a possibly increased risk of fetal wastage. Published information
      regarding the role and safety of ERCP in pregnancy is limited. This series of 23
      pregnant patients undergoing ERCP was collected from six different medical
      centers. METHODS: Twenty-three pregnant patients with symptomatic
      pancreaticobiliary disease underwent a total of 29 ERCPs (three patients had
      diagnostic ERCP, and 20 had therapeutic ERCP). Fifteen, eight, and six procedures
      were performed in the first, second, and third trimesters, respectively. The only
      ERCP complication was pancreatitis in one patient. There was one spontaneous
      abortion (3 months after ERCP) and one neonatal death; however, casual
      relationship to ERCP was not apparent. CONCLUSION: Diagnostic and therapeutic
      ERCP appears reasonably safe and effective in pregnancy. Cautious and selective
      use of this procedure offers a viable alternative to surgery or observation in
      patients with emergent pancreaticobiliary problems.

PMID- 7639228
TI  - A study of the safety and clinical efficacy of esophagogastroduodenoscopy after
      esophageal, gastric, or duodenal surgery in 60 patients.
AB  - OBJECTIVES: Our purpose was to evaluate the safety of esophagogastroduodenoscopy
      (EGD) after esophageal, gastric, or duodenal surgery, a previously unstudied
      subject. EGD could promote suture breakdown at sites of anastomoses, ostia, or
      repair by abrasion or stretch from endoscopic intubation, torque, or
      insufflation. METHODS: Risks versus benefits of EGD performed within 24 days of
      upper gastrointestinal surgery were analyzed at five medical centers in 60 study
      patients and were compared with 120 controls matched for age, sex, and EGD
      indication. RESULTS: Of 13,170 hospitalized patients undergoing EGD, 60 patients
      (0.46%) had EGD within 24 days of upper gastrointestinal surgery. EGD indications
      in study patients included gross upper gastrointestinal bleeding in 24, nausea
      and vomiting in 23, bright red blood per rectum in four, dysphagia in three,
      abdominal pain in three, and "other" in three. EGD was performed on average 14.7
      +/- 7.2 (SD) days after surgery. EGD provided the diagnosis in 45 (75%) study
      patients (control rate = 77%, not significantly different, chi 2). In particular,
      postoperative EGD provided the diagnosis in 20 (83%) of 24 patients with upper
      gastrointestinal bleeding (control rate = 92%, not significantly different,
      Fisher's exact test). Thirteen study patients (22%) had upper gastrointestinal
      lesions directly related to surgery including: anastomotic ulcers in six,
      anastomotic erosions in six, and an excessively tight Nissen fundoplication in
      one. One additional patient at EGD had extrinsic duodenal compression attributed
      to postoperative adhesions. EGD led to surgery in nine and to successful
      endoscopic therapy in six. No study patient experienced an endoscopic
      complication. The control group had one endoscopic complication (not
      significantly different rates, Fisher's exact test). CONCLUSION: In this study,
      the benefits outweighed the risks of postoperative EGD when performed more than 7
      days after surgery: the diagnostic yield was high and the complication rate was
      low. Indeed, the yield and risks were similar to that of other EGDs.
      Postoperative EGD identified a surgical complication in about 20% of cases.
      Clinicians should use discretion and perform postoperative EGD for clinically
      important indications. EGD is contraindicated when wound dehiscence or bowel
      perforation is suspected.

PMID- 7639229
TI  - Effect of administration of ranitidine bismuth citrate with food on the
      suppression and eradication of Helicobacter pylori in infected volunteers.
AB  - OBJECTIVE: This study examined the effect of administration with food on the
      ability of ranitidine bismuth citrate to suppress and eradicate Helicobacter
      pylori in 41 infected volunteers. RESULTS: After a 7-day course of treatment with
      ranitidine bismuth citrate (400 mg b.i.d.), 90% (18/20) of subjects who received
      the drug with food compared with 55% (11/20) of subjects who received the drug
      without food tested H. pylori-negative in a 13C-urea breath test (p = 0.031).
      Follow-up 13C-urea breath tests performed at least 3 months after therapy showed
      that H. pylori was eradicated in 14% (2/14) of subjects who received ranitidine
      bismuth citrate with food compared with 0% (0/18) of subjects who received
      ranitidine bismuth citrate without food (p = 0.183). The incidence of potentially
      drug-related adverse events was similar regardless of whether subjects received
      ranitidine bismuth citrate with or without food. Headache was the most common
      potentially drug-related adverse event. CONCLUSIONS: These data demonstrate that
      administration of ranitidine bismuth citrate with food compared with without food
      significantly improves the suppression of H. pylori in infected volunteers.

PMID- 7639230
TI  - Helicobacter pylori in patients with gastric and nongastric cancer.
AB  - OBJECTIVES: To compare the seroprevalence of Helicobacter pylori in gastric and
      nongastric carcinoma patients and to investigate the relationship between H.
      pylori, gastric cancer site, and histological type. METHODS: In a 24-month
      period, 307 gastric cancer patients (male/female: 185/122; age range 19-94 yr,
      mean 69 yr) were investigated by serology (IgG to H. pylori), histology, and
      urease test for H. pylori. One hundred and seventy-seven gastric cancers were in
      the antrum, 98 were in the corpus, and 32 were in the fundus; 227 were intestinal
      and 80 were diffuse type. In the same study period, we assessed the H. pylori
      seroprevalence in 162 patients with nongastric carcinoma (lung n = 41, breast n =
      42, genitourinary n = 41, GI tract n = 22, others n = 16) (male/female: 84/78;
      age range 31-81 yr, mean 56 yr). RESULTS: The overall seroprevalence of H. pylori
      in gastric cancer and in nongastric cancer was 82 and 56%, respectively (p <
      0.001). In asymptomatic blood donors (age range 55-65 yr) and in dyspeptic
      patients older than 60 yr, a seroprevalence of 55 and 58% was found,
      respectively, which is significantly lower (p > 0.001) than the gastric cancer
      patients but similar to the nongastric cancer population. No difference was found
      in the H. pylori status according to the gastric cancer site (83, 82, and 81% in
      the antrum, corpus, and fundus, respectively). Two hundred and twenty-seven
      gastric cancers [185 (81%) H. pylori-positive] were found to be of an intestinal
      type and 80 [66 (82%) H. pylori-positive] of a diffuse type (not significant). No
      age-related difference (below and above 60 yr) in H. pylori prevalence was
      observed within each cancer population, and, in both age groups, the
      seroprevalence of infection was higher in gastric cancer patients (86 and 81%)
      than in nongastric cancer patients (56 and 56%) (below and above 60 yr,
      respectively). CONCLUSION: H. pylori seroprevalence is significantly higher in
      gastric cancer compared with nongastric cancer patients. No differences were
      observed in H. pylori seroprevalence according to gastric cancer site or
      histological type. The higher H. pylori seroprevalence in gastric cancer patients
      is not age related.

PMID- 7639231
TI  - Restriction fragment length polymorphism in the adhesin gene hpaA of Helicobacter
      pylori.
AB  - OBJECTIVES: To assess the degree of restriction fragment length polymorphism
      (RFLP) in the Helicobacter pylori adhesin gene hpaA and to determine the
      molecular basis of RFLP in this gene. METHODS: A 375-bp, polymerase chain
      reaction-amplified internal sequence of hpaA, obtained from 50 different H.
      pylori isolates, was restricted with Sau3A and HinfI, individually. Polymerase
      chain reaction products representing different RFLP types were sequenced.
      RESULTS: Seven different polymorphic types were found in hpaA. Base substitutions
      at only four positions, two in Sau3A and two in HinfI sites, account for all of
      the RFLP types, including the size of the restriction fragments determined by gel
      electrophoresis. Most, 90%, of the base substitutions are very conservative,
      i.e., either do not change the encoded amino acid or substitute a homologous
      amino acid, and cause no detectable antigenic or functional effect on hpaA. The
      region of hpaA encoding the receptor-binding motif was particularly well
      conserved. CONCLUSIONS: RFLP typing of hpaA using Sau3A and HinfI provides an
      additional tool for comparing the genetic relatedness of H. pylori isolates
      collected during epidemiological and/or treatment studies.

PMID- 7639232
TI  - Comparison of once daily doses of lansoprazole (15, 30, and 60 mg) and placebo in
      patients with gastric ulcer.
AB  - OBJECTIVES: A multicenter, double-blind study was conducted in 268 patients to
      compare the safety and efficacy of 15, 30, and 60 mg of lansoprazole and placebo
      in the treatment of gastric ulcer. METHODS: The study included an 8-wk treatment
      period to assess healing and a 6-month posttreatment period to evaluate ulcer
      recurrence. Endoscopies were performed, GI symptoms and antacid use were
      assessed, and safety evaluations were conducted, including serum gastrin and
      biopsies of the lesions and the greater curvature of the stomach. RESULTS: At
      week 4, healing rates were significantly higher with lansoprazole 15 and 30 mg
      (64.6 and 58.1%, respectively) compared with placebo (37.5%). By week 8, healing
      rates were 76.7% with placebo, 92.2% with 15 mg of lansoprazole, 96.8% with 30
      mg, and 93.2% with 60 mg of lansoprazole (p < 0.05). The drug was well tolerated,
      with no significant differences from placebo in the incidence of adverse events.
      Fasting serum gastrin increased in all lansoprazole groups, reaching a plateau by
      week 2 and returning to baseline levels by month 1 posttreatment. No significant
      increase in Grimelius-positive cells or inflammation was evident. All but two
      patients had normal gastric morphology evaluated by Solcia classification.
      CONCLUSIONS: Lansoprazole, 15, 30, and 60 mg, administered once daily before
      eating, healed gastric ulcers to an approximately equal degree, and all were
      significantly better than placebo.

PMID- 7639233
TI  - Delayed colonic transit in spinal cord-injured patients measured by indium-111
      Amberlite scintigraphy.
AB  - OBJECTIVE: Constipation is a major problem for patients with chronic spinal cord
      injury (SCI). However, it is not clear whether abnormal colonic transit is
      restricted to the rectosigmoid region or involves the entire colon. We assessed
      regional colonic transit with emphasis on the ascending and transverse segments
      in patients with chronic SCI and compared the results with those of controls
      using scintigraphic techniques. METHODS: Seven patients with SCI below T1 and 10
      control subjects were studied after oral ingestion of a capsule containing indium
      111-labeled Amberlite (Sigma Chemical, St. Louis, MO) pellets. The capsule was
      coated with a pH-sensitive polymer that prevents disintegration until it reaches
      the ileocecal region. Assessments of the half-time of emptying and residence time
      of contents in ascending and transverse segments were made, as well as an
      assessment of the velocity of contents throughout the entire colon, including the
      descending colon. RESULTS: A significantly slower half-time of emptying was found
      in SCI patients (ascending: 29 +/- 27 hr in SCI, 6.81 +/- 3.03 hr in controls, p
      < 0.01; ascending + transverse: 42 +/- 12 hr in SCI, 15.3 +/- 7.16 hr in
      controls, p < 0.01). The residence time of the median position of the contents
      was significantly prolonged in SCI patients (ascending: 31 +/- 23 hr in SCI, 8.75
      +/- 4.68 hr in controls, p < 0.05; transverse: 26 +/- 3 hr in SCI, 5.0 +/- 4.4 hr
      in controls, p < 0.05). Overall, the velocity of the median position of contents
      throughout the entire colon was significantly lower in SCI (0.63 +/- 0.33 cm/hr
      in SCI, 2.58 +/- 1.20 cm/hr in controls, p < 0.001). CONCLUSIONS: Patients with
      chronic SCI have prolonged colonic transit that involves the entire colon. Hence,
      treatment of constipation in these patients may need to include prokinetic agents
      as well as local rectal maneuvers.

PMID- 7639234
TI  - Circulating soluble interleukin-2 receptor alpha and beta chain in inflammatory
      bowel disease.
AB  - OBJECTIVES: Inflammatory bowel disease is characterized by T cell activation.
      Activated T cells shed interleukin-2 receptors (IL-2R) in a soluble form. A
      positive correlation between sIL-2R alpha (CD25) and disease activity in
      inflammatory bowel disease has been shown previously, whereas IL-2R beta (CD122)
      has never before been investigated in this respect. Serum from 27 patients with
      ulcerative colitis (UC), 31 with Crohn's disease (CD), and 29 healthy volunteers
      was obtained. METHODS: Disease activity was scored according to a
      semiquantitative score for UC and by Crohn's disease activity index for CD. sIL
      2R alpha and -beta chains were assessed by a sandwich ELISA technique using
      monoclonal antibodies specific for CD25 and CD122, respectively. RESULTS: The
      median concentration of sIL-2R alpha was 4424 pg/ml in healthy controls, 6460 in
      UC (p < 0.004), and 6371 in CD (p < 0.01). The corresponding value of sIL-2R beta
      in healthy volunteers was 605 pg/ml; in active UC, significantly lower levels
      were found at 233 pg/ml (p < 0.01), whereas in inactive UC, no such difference
      was observed at 725 pg/ml (p > 0.05). In CD, the levels were 839 pg/ml in
      inactive and 920 pg/ml in active disease stages (p > 0.05 vs controls). A
      positive and significant correlation existed between sIL-2R levels of alpha and
      beta chains in CD (r = 0.64; p < 0.01) but not in UC (r = -0.32; p > 0.05) or in
      healthy volunteers (r = 0.16; p > 0.05). CONCLUSION: Future longitudinal studies
      will be necessary to learn whether this newly assessed sIL-2R beta (CD122), which
      may interfere with IL-15R, could be used to predict disease exacerbation and to
      monitor anti-inflammatory therapy in UC.

PMID- 7639235
TI  - Reevaluation of prognostic factors in gastric leiomyosarcoma.
AB  - OBJECTIVES: The aim of our study was to reevaluate the prognostic factors in
      gastric leiomyosarcomas, particularly those under 6 cm, which, because of
      improved diagnostic techniques, make up a large proportion of this series, in
      contrast to previously published works. METHODS: The clinicopathological features
      in 83 patients with gastric leiomyosarcoma were reviewed. Cox's proportional
      hazards regression analysis was used to determine the prognostic factors.
      RESULTS: Sixty of 84 leiomyosarcomas (71.4%) were less than 6 cm in diameter. In
      univariate analysis, the following factors were considered to be unfavorable,
      with statistical significances: 1) presence of distant metastasis and/or direct
      invasion of adjacent structures at diagnosis (hazard ratio 36.60), 2) > or = 4
      mitoses per 20 high-power fields (25.39), 3) severe nuclear atypia (16.74); 4)
      presence of ulceration of overlying gastric mucosa (12.57), and 5) diameter > or
      = 6 cm (5.57). Among these factors, mucosal ulceration has been identified as a
      new factor associated with poor prognosis. Histologically, the tumors with
      ulceration showed more severe nuclear atypia (p < 0.05), necrosis (p < 0.01), and
      a higher incidence of mitosis (p < 0.01), compared with tumors without
      ulceration. In multivariate analysis, factors 1, 2, and 3 were statistically
      significant, although neither size nor ulceration was significant. CONCLUSIONS:
      The presence of distant metastasis and/or direct invasion, high mitotic rate, and
      severe nuclear atypia were confirmed to be unfavorable prognostic indicators.
      Mucosal ulceration, indicating high proliferative activity of the tumor, even if
      small, suggests a poor prognosis, although it was not significant in multivariate
      analysis.

PMID- 7639236
TI  - Disorders of the rectus abdominis muscle and sheath: a 22-year experience.
AB  - OBJECTIVES: To determine the spectrum of diseases that can involve the rectus
      abdominis muscle and sheath (RMS) and to describe the clinical features of these
      conditions. METHOD: A retrospective medical record review of RMS disorders seen
      at The New York Hospital-Cornell Medical Center from 1971 to 1992. RESULTS: A
      total of 40 patients with diseases of the RMS were identified. Thirty patients
      had primary diseases of the RMS, most commonly desmoid tumor and hematoma.
      Secondary disorders of the RMS included abscesses from diverticulitis, a
      perforated sigmoid carcinoma, gallbladder empyema, and disseminated
      actinomycosis. Eleven of 18 patients with desmoid tumors had familial adenomatous
      polyposis (FAP). The desmoid tumors in patients with FAP resulted in greater
      morbidity and mortality than those in patients without FAP. All patients with
      hematomas were on anticoagulation or had a history of trauma, vigorous coughing,
      or physical exertion. CONCLUSIONS: 1) RMS disease should be suspected in patients
      with a palpable abdominal mass and a history of familial adenomatous polyposis,
      trauma, anticoagulation, or vigorous coughing or exercise. 2) The most common non
      neoplastic condition of the RMS is a hematoma. 3) The desmoid tumor is the most
      common neoplasm of the RMS. 4) Abdominal ultrasonography and CT readily
      distinguish RMS disease from intraabdominal pathology.

PMID- 7639237
TI  - Botulinum toxin for suspected pseudoachalasia.
AB  - We describe a 74-yr-old man with stage III adenocarcinoma of the lung who
      presented with suspected malignancy-induced secondary achalasia and responded
      clinically to intrasphincteric injections of botulinum toxin type A (Botox,
      Allergen Inc., Irvine, CA). We discuss the use of botulinum toxin in this
      setting, as well as diagnostic strategies to differentiate achalasia from
      pseudoachalasia.

PMID- 7639238
TI  - Advantages of sphincterotomy and nasobiliary tube drainage in the treatment of
      cystic duct stump leak complicating laparoscopic cholecystectomy.
AB  - We have used sphincterotomy and nasobiliary tube drainage in preference to other
      forms of endoscopic therapy to manage three cases of cystic duct stump leak
      complicating laparoscopic cholecystectomy. The ability to monitor daily
      nasobiliary tube output and to perform repeat cholangiograms without subjecting
      the patients to multiple endoscopies permitted precise determination of cystic
      duct stump leak closure and timely discharge. We observed that an approximate
      doubling of the 24-h nasobiliary tube output coincided with closure of the cystic
      duct stump leak at cholangiography. Bile ascites was present in two of the cases
      and was conveniently removed by CT-guided placement of peritoneal drains. All
      cystic duct stump leaks sealed after 5 days of nasobiliary tube drainage. The
      advantages of sphincterotomy and nasobiliary tube drainage include precise
      determination of cystic duct leak closure, final device removal without follow-up
      endoscopy, and ongoing decompression of the biliary tree after removal of the
      nasobiliary tube.

PMID- 7639239
TI  - Massive gastrointestinal hemorrhage during pregnancy caused by ectopic decidua of
      the terminal ileum and colon.

PMID- 7639240
TI  - Endoscopic therapy of a bleeding duodenal diverticulum.

PMID- 7639241
TI  - A case of Peutz-Jeghers syndrome with nasal polyposis, extreme iron deficiency
      anemia, and hamartoma-adenoma transformation: management by combined surgical and
      endoscopic approach.
AB  - We report a rare variant of Peutz-Jeghers syndrome identified by the presence of
      nasal polyposis and extreme anemia. Multiple hamartomatous polyps were found
      throughout the upper and lower gastrointestinal tract. We conducted a combined
      surgical-endoscopic approach to prevent the development of a short-bowel
      syndrome. The polyps removed by snare and surgical polypectomy showed features
      typical of harmartomas. Three colonic polyps and two nasal polyps showed
      histological evidence of adenomatous change. This adenomatous change seems to fit
      into the pathogenic sequence of hamartoma-adenoma.

PMID- 7639242
TI  - Acalculous candidal cholecystitis: a previously unrecognized complication after
      cardiac transplantation.
AB  - Acalculous cholecystitis is a life-threatening complication in critically ill
      surgical patients. Whereas Candida albicans and Torulopsis glabrata have been
      reported as the primary pathogens in 14 previous cases of acalculous
      cholecystitis, we report the first case of Candida parapsilosis as a biliary
      pathogen in a patient after cardiac transplantation. Although cardiac transplant
      recipients often have many of the risk factors for acalculous candidal
      cholecystitis, including major surgery, immunosuppression, antibiotic therapy,
      parenteral nutrition, and prolonged intensive care unit stay, this entity has not
      been previously reported in the cardiac transplant population. Although rare,
      acalculous candidal cholecystitis is associated with very high morbidity and a
      mortality rate of 40%. Early diagnosis necessitates an aggressive approach to the
      critically ill patient with abdominal complaints. Prompt drainage or
      cholecystectomy, if possible, represent the mainstays of therapy and offer the
      greatest chance for survival.

PMID- 7639244
TI  - A fatal complication related to gastrostomy button placement.

PMID- 7639243
TI  - Retroperitoneal leiomyosarcoma and gastroparesis: a new association and review of
      tumor-associated intestinal pseudo-obstruction.
AB  - Intestinal pseudo-obstruction has been associated with several types of
      underlying neoplasms and has been hypothesized to result from a paraneoplastic
      process in patients with small cell lung carcinoma and bronchial carcinoid. This
      article documents the first reported association of gastroparesis and a
      retroperitoneal leiomyosarcoma. A paraneoplastic process is the proposed basis of
      this relationship, inasmuch as these syndromes have been noted in other tumors of
      mesodermal origin. The resolution of intestinal dysmotility after tumor
      resection, as described here, has only rarely been reported.

PMID- 7639245
TI  - Adenocarcinoma of the colon presenting as Streptococcus sanguis bacteremia.

PMID- 7639247
TI  - Biliary phytobezoar: a medical curiosity.
AB  - This report describes a case of cholestatic jaundice caused by concretions of
      vegetable material obstructing the extrahepatic bile ducts. We have named this a
      biliary phytobezoar, by analogy with its gastric counterpart. The anomaly
      underlying this curiosity was a surgical cholecystogastrostomy performed 15 yr
      earlier.

PMID- 7639246
TI  - A case of hepatocellular adenomatosis with a follow-up of 11 years.
AB  - Hepatocellular adenomatosis is characterized by the presence of numerous
      (arbitrarily > 10) adenomas within an otherwise normal liver without a history of
      glycogen storage disease or steroid hormone therapy. Although the disease is
      rare, its importance lies in its tendency to produce symptoms such as abdominal
      pain and its potential for abdominal hemorrhages. However, the prognosis of
      hepatocellular adenomatosis remains uncertain. Here we describe the case of a 40
      yr-old female with hepatocellular adenomatosis without evidence of serious
      complications, who was observed over a period of 11 yr.

PMID- 7639248
TI  - Esophagocardioplasty for achalasia in closure of a complicated esophagobronchial
      fistula.
AB  - We report a rare case of benign esophagobronchial fistula associated with
      achalasia. The fistula healed spontaneously after esophagocardioplasty with a
      gastric patch, suggesting the utility of this procedure.

PMID- 7639249
TI  - Primary gastric plasmacytoma of rapid growth presenting with upper
      gastrointestinal bleeding.
AB  - We report a new case of primary gastric plasmacytoma. The presenting symptoms was
      upper gastrointestinal bleeding, and the diagnosis was made preoperatively by
      means of gastroscopically obtained biopsy material. The demonstration of a single
      type of IgA-kappa immunoglobulin in plasma cells infiltrating the gastric antrum
      is considered conclusive evidence of its neoplastic nature. Endoscopically, the
      gastric plasmacytoma progresses from a benign antral ulcer (0.5 cm in diameter)
      to an ulcerated mass (7 cm in diameter) in an 8-wk period, suggesting rapid
      tumoral growth of a kind not described in the revised literature.

PMID- 7639250
TI  - Severe diarrhea due to Cokeromyces recurvatus in a bone marrow transplant
      recipient.
AB  - Cokeromyces recurvatus, a sporangiola-forming dimorphic fungus, is a rare cause
      of urogenital infection in humans. We report here a case of severe watery
      diarrhea due to C. recurvatus, which was treated successfully with high-dose oral
      nystatin therapy. We speculate that our patient was probably predisposed to
      infections due to opportunistic organisms, such as C. recurvatus, because of post
      transplantation immunosuppression. To our knowledge, our patient represents the
      first documented case of diarrhea due to C. recurvatus in man, and this case
      highlights the potential pathogenic capability of this opportunistic organism in
      immunosuppressed patients.

PMID- 7639251
TI  - Treatment of hepatocellular carcinoma with transjugular intrahepatic
      portosystemic shunting and chemoembolization.

PMID- 7639252
TI  - The enigma of achalasia.

PMID- 7639253
TI  - Gastrointestinal bleeding in the critically ill: a penny saved....

PMID- 7639254
TI  - Dispar makes its debut.

PMID- 7639255
TI  - Long-term results of heater probe treatment for ulcer bleed.

PMID- 7639256
TI  - Gastrointestinal motility and Helicobacter pylori infection in nonulcer
      dyspepsia.

PMID- 7639257
TI  - Trachesophageal fistula complicating placement of a self-expanding metallic
      tracheal stent.

PMID- 7639258
TI  - The endoscopic appearance of eosinophilic gastroenteritis in infancy.

PMID- 7639259
TI  - Inflammatory cloacogenic polyp and solitary rectal ulcer syndrome resemble rectal
      adenocarcinoma.

PMID- 7639260
TI  - Liver abscesses as initial presentation of Crohn's disease.

PMID- 7639261
TI  - So-called "autoimmune hepatitis type IIb" is not categorized in autoimmune
      hepatitis.

PMID- 7639262
TI  - Is there a relationship between hypergastrinemia and colorectal cancer risk?
      Rectal cell proliferation in Zollinger-Ellison syndrome.

PMID- 7639263
TI  - Right corpus cavernosum metastasis of a left colonic adenocarcinoma.

PMID- 7639264
TI  - Antithyroid peroxidase antibody and development of silent thyroiditis during
      interferon-alpha 2a treatment of chronic hepatitis C.

PMID- 7639265
TI  - Gastrointestinal transit in alcoholic cirrhosis.

PMID- 7639266
TI  - Absence of seasonal variations in peptic ulcer activity and bleeding from peptic
      ulcer.

PMID- 7639267
TI  - A case of esophageal dysplasia associated with human papilloma virus.

PMID- 7639268
TI  - Pseudomonas aeruginosa-induced toxic enteritis (Pseudomonas enteritis) in a
      postoperative patient with sigmoid colon cancer and bronchiectasis associated
      with antibiotic and H2-blocker administration.

PMID- 7639269
TI  - Presence of sebaceous glands in the esophagus.

PMID- 7639271
TI  - Low proteins C and S and activation of fibrinolysis in treated essential
      thrombocythemia.
AB  - The aim of this study was to investigate whether abnormalities in the
      fibrinolytic system and in the naturally occurring anticoagulant proteins could
      contribute to the thrombotic risk in essential thrombocythemia. Euglobulin lysis
      time, fibrin plate lysis area, tissue plasminogen activator antigen, and activity
      and plasminogen activator inhibitor antigen were measured before and after venous
      occlusion in a group of 16 patients with essential thrombocythemia and in 16
      healthy age and sex matched controls. In addition, resting levels of antithrombin
      III, D-dimer, prothrombin fragment 1 + 2, and protein C and S were assessed. The
      results were related to the presence or absence of a thrombotic history. The
      results demonstrated that the patients had a significantly elevated fibrin plate
      lysis area and significantly decreased plasminogen activator antigen, both at
      baseline and after venous occlusion. They also had significantly decreased levels
      of plasma protein C and total protein S. There was a modest, non-significant
      elevation in the plasma concentration of D-Dimer and F 1 + 2. Those patients with
      a history of thrombosis had significantly lower protein C levels compared with
      individuals without a thrombotic history. We conclude that patients with
      essential thrombocythemia have evidence of activated fibrinolysis in the resting
      state and after stimulation. This, and the decreased levels of protein C and
      total protein S, may be secondary to chronic clinically occult thrombosis
      occurring in myeloproliferative disorders.

PMID- 7639270
TI  - Abnormal gamma IFN and alpha TNF secretion in purified CD2+ cells from autoimmune
      thrombocytopenic purpura (ATP) patients: their implication in the clinical course
      of the disease.
AB  - Gamma inferferon (gamma IFN), alpha tumor necrosis factor (alpha TNF), and
      interleukin 6 (IL-60) are cytokines produced by a wide variety of cells,
      including T lymphocytes and NK cells. These cytokines affect B-cell proliferation
      and differentiation into immunoglobulin secreting cells. In addition, gamma IFN
      and alpha TNF also enhance the function of macrophages, upregulating the
      expression of their IgG receptors. Abnormalities in the production of these
      cytokines may be involved in the clinical course of autoimmune thrombocytopenic
      purpura (ATP). This paper describes the production of these cytokines in PHA
      stimulated peripheral blood CD2+ cells from ATP patients. Both gamma IFN and
      alpha TNF were significantly increased in PHA-stimulated CD2+ cells from therapy
      dependent ATP patients (platelet counts < 50,000/microliter), as compared to ATP
      patients with stable disease (sustained platelet counts < 50,000/microliter
      without need treatment) (P < 0.05). No significant differences were found in
      gamma IFN production by PHA-stimulated CD2+ cells between therapy-dependent ATP
      patients and healthy controls (P < 0.05). However, the production of alpha TNF by
      PHA-stimulated CD2+ cells from therapy-dependent ATP patients was significantly
      higher compared to that found in healthy controls (P < 0.05). There were no
      significant differences in IL-6 production by PHA-stimulated CD2+ cells from ATP
      patients and healthy controls (P < 0.05). These findings demonstrate abnormal
      gamma IFN and alpha TNF secretion in purified CD2 cells from ATP patients. The
      clinical severity of the disease is associated with the altered secretion of
      these lymphokines by CD2 cells.

PMID- 7639272
TI  - Anabolic-androgenic steroid abuse in weight lifters: evidence for activation of
      the hemostatic system.
AB  - Anabolic-androgenic steroid abuse has recently been linked with acute vascular
      events in athletes. To date, the relationship between steroid abuse and the
      potential for cardiovascular disease has been considered almost exclusively in
      terms of lipid metabolism. However, recent reports of thrombosis in androgen
      abusing athletes with no evidence of atherosclerosis suggests the hypothesis that
      thrombosis risk in such athletes could be mediated through androgen induced
      abnormalities of coagulation. To determine if anabolic-androgenic steroid abuse
      in weight lifters is associated with an activation of the hemostatic system we
      studied forty-nine weight lifters recruited through advertisements. History of
      androgen use or abstinence was confirmed via urine assays. Plasma was assayed for
      clotting and fibrinolytic activity by measuring thrombin/antithrombin complexes
      (TAT), prothrombin fragment 1 + 1 (F1 + 2), and D-dimers (D-di); markers of the
      endothelial based fibrinolytic components were assayed by measuring tissue
      plasminogen activator antigen (t-PA Ag) and its inhibitor (PAI-1); finally, the
      activity of antithrombin III, protein C, and protein S were measured. Abnormally
      high concentrations of TAT complexes were noted in 16% of our confirmed steroid
      using weight lifters compared to 6% of our confirmed nonusers (P = .01). Steroid
      users also demonstrated abnormally high concentrations of F1 + 2 and D-dimers
      when compared to nonusers (44 vs. 24%, P < .001, and 9 vs. 0%, respectively). Non
      steroid users were more likely to have elevated levels of t-PA Ag and PAI-1 than
      our steroid using weight lifters (both P < .001). The activities of antithrombin
      III and protein S were more likely to be higher in users compared to nonusers (22
      vs. 6%, P = .005; 19 vs. 0%, respectively). Some anabolic-androgenic steroid
      using weight lifters have an accelerated activation of their hemostatic system as
      evidence by increased generation of both thrombin and plasmin. These changes
      could reflect a thrombotic diatheses that may contribute to vascular occlusion
      reported in young athletes using these drugs. The predictive value of these
      coagulation abnormalities in terms of risk of thrombosis to individual steroid
      using weight lifters or the population as a whole remains to be studied.

PMID- 7639273
TI  - Platelet von Willebrand factor abnormalities in myeloproliferative syndromes.
AB  - Plasma and platelet von Willebrand factor (vWF) measurements, multimeric pattern
      and subunit composition of plasma vWF were obtained in 29 consecutive patients
      with chronic myeloproliferative syndromes. In the 8 patients with chronic
      myelogenous leukemia (CML), plasma vWF was significantly higher than in the 11
      patients with essential thrombocythemia (ET) and in the 10 patients with
      polycythemia vera (PV). The RiCof/vWF:Ag ratio was low in all these groups of
      patients (mean 0.64 +/- 0.1, 0.66 +/- 0.2, and 0.61 +/- 0.2; normal 0.97 +/-
      0.2). Bleeding time was prolonged (> 7.5 min) in 1/8 CML patients, 1/10 with PV,
      and 3/11 with ET. Plasma vWF multimers showed a minor loss of the largest
      multimers in 3/8 patients with CML, 4/10 with PV, and a more severe reduction in
      9/11 ET patients. The latter pattern correlated with an abnormal proteolysis of
      vWF, expressed by a major increase of the 140-Kd fragment and decrease of the
      intact 225-Kd subunit in ET patients, whereas the 176-Kd fragment was
      significantly increased in all the subgroups of patients. Platelet vWF was
      significantly higher in CML patients in comparison to ET and normal controls.
      However, minor losses of the larger multimers were evident in all the subsets of
      patients. In ET patients also the intermediate forms were lacking in platelets,
      accompanied by a significant decrease of platelet RiCof. This abnormality was
      significantly correlated with the occurrence of bleeding symptoms in PV and ET
      patients (P = 0.007; Fisher's exact test). In conclusion, plasma and platelet vWF
      abnormalities are common findings in myeloproliferative syndromes and are more
      severe in ET. The more pronounced platelet vWF abnormalities in ET may reflect
      the more frequent bleeding symptoms observed in this disorder.

PMID- 7639274
TI  - Molecular characterization of a new family with alpha-thalassemia-1 (--MA
      mutation).
AB  - A Spanish family with alpha-thalassemia-1 (alpha-Thal-1), deletion (--MA), is
      described. In addition to the loss of 22 kb of DNA with a deletion of the alpha
      1, alpha 2, psi alpha 2, and psi zeta 1 genes, a triplication of the zeta gene
      cluster in "cis" is produced. The structure of this triplication is formed by the
      psi zeta 1 gene, the interzeta region, and, possibly, the insertion of the psi
      alpha 2 fragment.

PMID- 7639275
TI  - Discordant morphologic features in bone marrow involvement by malignant
      lymphomas: use of gene rearrangement patterns for diagnosis.
AB  - Discordant morphology between lymph node or extra-nodal site and bone marrow (BM)
      involvement by non-Hodgkin's malignant lymphoma (NHL) is a common occurrence,
      causing diagnostic difficulties. Additional diagnostic problems are posed by
      lymphoid aggregates commonly found in the BM of elderly patients, the age group
      with the highest incidence of lymphoma. Morphologic features are used to
      distinguish between benign and malignant lesions but no feature is diagnostic and
      exceptions are numerous. Immunophenotyping is helpful for detecting B cell
      monoclonality, but it cannot detect T cell monoclonality. Unique B and T cell
      gene rearrangement patterns, the molecular "signature" of the lymphoma, can be
      used to detect monoclonal lymphoid populations. Finding the same rearrangement
      pattern in the BM as in the primary mass is proof of BM involvement by the same
      clone of malignant cells. We used B/T and Bcl-2 gene rearrangements to help
      diagnose cases with discordant morphology between primary site and BM. One
      hundred and seventy-five specimens, obtained from patients undergoing staging or
      restaging for NHL, were analyzed for B/T cell and Bcl-2 gene rearrangements by
      multiple restriction endonuclease digestion and Southern hybridization with 32P
      labeled JH, JK, CT beta, and Bcl-2 probes. Forty-two specimens (24%) from 24
      patients showed discordant morphology: of 13 specimens with atypical lymphoid
      aggregates, only one had B cell gene rearrangement; of 15 specimens with
      morphologically benign lymphoid aggregates, one demonstrated B cell gene
      rearrangement; and of 14 specimens positive for NHL with different morphology
      than the lymph node, 13 were positive for B cell gene rearrangements. Molecular
      analysis can aid in the diagnosis of NHL, can establish a "baseline" for
      detection of recurrence, and is useful in monitoring therapy. These data suggest
      that it is also a tool for the pathologist in cases of discordant morphology
      between the primary tumor and BM, and should be strongly considered for each
      site.

PMID- 7639276
TI  - Autoantibody to factor VIII that has less reactivity to factor VIII/von
      Willebrand factor complex.
AB  - To determine the difference in reactivity of factor VIII (FVIII) inhibitor to
      FVIII/von Willebrand Factor (vWF) complex and FVIII free of vWF, an autoantibody
      to FVIII light chain was tested. A patient (1-3) suffered from autoimmune
      hemolytic anemia with autoantibody to FVIII. Epitope specificity of the patient's
      IgG (I-3 IgG) was shown to be the C2 domain of FVIII light chain (2170-2332) by
      Western blotting using recombinant FVIII deletions expressed in Escherichia coli.
      The inhibitory effect on FVIII procoagulant activity (VIII:C) of I-3 IgG was
      tested against a conventional FVIII concentrate; Haemate P, a monoclonal antibody
      purified FVIII concentrate; Hemofil M, and a recombinant FVIII (rFVIII);
      Kogenate. I-3 IgG showed only 1.3 BU/mgIgG for Haemate P, in contrast to 20
      BU/mgIgG for both Hemofil M and Kogenate. The ratio of VIII:C/vWF:Ag in Haemate P
      and Hemofil M was 1/3.43 and 1/0.01, respectively, while Kogenate did not contain
      vWF. The inhibitory effect of the I-3 IgG was then compared with Kogenate and its
      complex with vWF. The inhibitory effect was decreased against the rFVIII by
      forming a complex with vWF from 22 BU/mgIgG to 0.5 BU/mgIgG. Fab from the I-3 IgG
      had the same effect. In addition, vWF showed a protective effect on FVIII
      inactivation by the I-3 IgG in a dose dependent manner. Fifty-nine percent of
      residual VIII:C was retained in the presence of 8 U/ml of vWF after 1 hr
      incubation with I-3 IgG. These results suggested that vWF could compete with the
      I-3 IgG for binding to FVIII.

PMID- 7639277
TI  - Clinical correlates of subnormal vitamin B12 levels in patients infected with the
      human immunodeficiency virus.
AB  - OBJECTIVES: To determine the prevalence and describe the clinical correlates of
      subnormal cobalamin levels in subjects infected with the human immunodeficiency
      virus (HIV), and to assess its relationship to virus-mediated immunosuppression
      and/or anti-viral therapy. SETTING: Outpatient referral clinic in tertiary care
      hospital. PATIENT POPULATION: 200 HIV infected individuals. STUDY DESIGN:
      Descriptive cross sectional survey, with prospective follow-up in a subgroup of
      patients before and after initiation of zidovudine therapy. MEASURES: Routine
      complete blood count, serum B12 assay, CD4 counts. Serum homocysteine levels, and
      Schilling tests were performed on subgroups of study subjects. RESULTS: Subnormal
      serum B12 levels were found in 61 subjects (30.5%). B12 deficient subjects were
      more likely to be taking zidovudine. (P = .007). Serum homocysteine levels were
      significantly higher in patients with subnormal cobalamin levels but were
      unrelated to CD4 counts or zidovudine use, and were rarely outside of the normal
      range. Malabsorption of vitamin B12 as evidenced by abnormal Schilling tests was
      more likely among patients with more advanced HIV disease, or gastrointestinal
      symptoms but was not necessarily associated with low B12 levels. CONCLUSIONS:
      Decreased cobalamin levels are found frequently in HIV disease, especially among
      those treated with zidovudine. Evidence of B12 malabsorption is found among those
      with more advanced disease and gastrointestinal symptoms.

PMID- 7639278
TI  - Multidrug transporter P-glycoprotein 170 as a differentiation antigen on normal
      human lymphocytes and thymocytes: modulation with differentiation stage and
      during aging.
AB  - P-glycoprotein 170 (P-gp), the multidrug transport pump, excludes drugs from the
      interior of cells and is inhibited by agents such as cyclosporin A (CsA),
      verapamil, and FK-506, which are also substrates for the P-gp pump. This work
      documents the age- and differentiation-related changes in P-gp on T and B
      lymphocytes from human blood or spleen, and its absence on most thymus and bone
      marrow cells. Analysis of rhodamine 123 (Rh123) dye efflux, and its inhibition by
      cyclosporin A, was used as a quantitative measure of functional P-gp, and
      reactivity with MRK-16 was used as a measure of P-gp surface expression. The dye
      efflux and phenotypic expression of P-gp+ PBMC appeared equivalent to that of a
      moderately drug-resistant cell line, although efflux is prolonged. The
      sensitivity to inhibition by CsA, cyclosporin G (CsG), and PSC833 of P-gp on
      PBMC, thymocytes, or T-cell lines varied with apparent cell-type specificity.
      Normal blood and splenic T- or B-cells included 50-80% of cells with surface P-gp
      (MRK-16+), which mediated CsA-sensitive dye export. The proportion of P-gp+ T-
      and B-cells was lowest among children under age 10 years, increased in adulthood,
      and decreased after age 60. Thymus included 30% of P-gp+ cells mediating CsA
      sensitive dye export, including CD3-4-8- progenitors and mature CD3hi CD4+8- or
      CD4-8+ thymocytes. Mature T-cells in cord or adult blood, spleen, and bone marrow
      included a large proportion (50-60%) with efficient CsA-sensitive dye export,
      preferentially among the CD45RA+ subset. Monocytes from all tissue sources, and
      most bone marrow cells, expressed surface P-gp but retained Rh123, suggesting the
      absence of a functional dye export mechanism. In vitro mitogen-stimulated PBMC T
      and B lymphocytes lost P-gp function within 4-24 hr, consistent with the
      observation that P-gp was reduced on antigen-experienced CD45R0+ T-cells in vivo.
      Drug export by P-gp may protect lymphocytes from toxic effects of CsA, and may
      contribute to the immunosuppressive effects of such drugs. The developmentally
      regulated expression of P-gp function on lymphocytes, and its modulation on
      activated T- or B-cells, suggest an important role in normal immune development.

PMID- 7639279
TI  - Immune mediated agranulocytosis and anemia associated with thymoma.
AB  - Thymoma has been associated with a variety of autoimmune disorders. We report a
      case of agranulocytosis and anemia in a 68-year-old woman with a spindle cell
      thymoma. She was unresponsive to treatment with antibiotics, granulocyte-colony
      stimulating factor (G-CSF), prednisone, and high-dose intravenous immunoglobulin.
      Serial bone marrow examinations on this therapy showed progression from a
      cellular marrow with mild myeloid and erythroid hyperplasia and lymphocytosis, to
      granulocyte aplasia and severe erythroid hypoplasia. Her serum contained
      granulocyte-specific antibodies and inhibited the growth in culture of her own
      marrow cells and marrow cells from a normal donor. An IgG fraction from her serum
      also inhibited the growth of marrow cells. Although the patient's spindle cell
      thymoma was surgically removed, she remained neutropenic. She was treated with
      six plasma exchanges followed by 1,000 milligrams of intravenous cyclophosphamide
      2 days after the final plasma exchange and daily G-CSF. Three weeks later her
      peripheral blood showed marked leukocytosis with pronounced neutrophilia and a
      left shift. Although her agranulocytosis resolved, she died of fungal sepsis.
      This case demonstrates that aggressive plasma exchange and immunosuppressive
      therapy may benefit patients with agranulocytosis associated with thymoma.

PMID- 7639280
TI  - Late appearance of the Philadelphia chromosome with monosomy 7 in a patient with
      de novo AML with trilineage myelodysplasia.
AB  - We report here a patient with de novo acute myelocytic leukemia with trilineage
      myelodysplasia (AML/TMDS) in whom cytogenetic analysis was normal at diagnosis
      and in whom Philadelphia chromosome (Ph1) with monosomy 7 emerged at the terminal
      stage of the disease. Reverse transcription polymerse chain reaction (RT-PCTR) on
      the Ph1 positive specimen detected the mRNA encoding p190bcr/abl but did not
      detect mRNA encoding p210bcr/abl. However, mRNA encoding p190bcr/abl was not
      detected at diagnosis and or at relapse. These observations support the
      hypothesis that late-appearing Ph1 and monosomy 7 might be the result of clonal
      evolution during the course of leukemia, and p190bcr/abl might play a role in the
      terminal transformation or progression of leukemia.

PMID- 7639281
TI  - Antibody to annexin V has anti-phospholipid and lupus anticoagulant properties.
AB  - Anti-annexin V (anti-ANXV) IgG and lupus anticoagulant (LAC) were both shown to
      be capable of inducing apoptosis in umbilical vein endothelial cells [Nakamura et
      al.: Biochem Biophys Res Commun 205:1488-1493, 1994]. In the present study, we
      have demonstrated that anti-ANXV IgG prolongs the activated partial
      thromboplastin time and has an affinity for phospholipids in enzyme-linked
      immunosorbent assay. This indicates overlapping of anti-ANXV and LAC activities,
      suggesting that ANXV may be involved in the autoimmune mechanism for LAC
      production.

PMID- 7639282
TI  - Cytokine profile in acute myelofibrosis associated with aggressive large granular
      lymphocyte leukemia.
AB  - We report a patient with acute large granular lymphocyte (LGL) leukemia,
      presenting as acute myelofibrosis (AMF). The leukemic cells were immature T-cells
      (CD5+, CD7+, CD16-, CD56-, CD57-, and CD41-), had monosomy 7, and secreted large
      amounts of Transforming Growth Factor-beta 1(TGF-beta 1). The serum levels of
      interleukins (IL)-2, -2R, -6 and -8 were elevated, while the IL-1 beta, IL-4, and
      tumor necrosis factor-alpha were normal.

PMID- 7639283
TI  - Dexamethasone in the treatment of meningeal leukemia.
AB  - To determine if dexamethasone has a role in the treatment of meningeal leukemia,
      8 consecutive patients with acute lymphoblastic and signs or symptoms of CNS were
      included in the study. After the confirmation of leukemic blast cells on
      cerebrospinal fluid, they received intrathecal and IV dexamethasone; 3 days later
      the patients received "triple" intrathecal chemotherapy with dexamethasone,
      methotrexate and cytarabine, and the spinal fluid was studied again. All patients
      had good clinical response and 7 out of the 8 patients showed reduction on the
      CSF cell count after the use of dexamethasone alone. The results suggest that
      dexamethasone is a lymphocytic agent that could play a more active role in the
      prevention and therapy of meningeal leukemia and should be preferred over
      hydrocortisone in the so called "triple" intrathecal chemotherapy for the
      prevention and treatment of CNS leukemia.

PMID- 7639285
TI  - Autoimmune hemolytic anemia in a patient with idiopathic hypereosinophilia.

PMID- 7639284
TI  - Minimal change glomerulonephritis with reversible proteinuria during interferon
      alpha 2a therapy for chronic myeloid leukemia.

PMID- 7639286
TI  - Third case of acute monocytic leukemia (M5) occurring in an HIV-seropositive man:
      a case report.

PMID- 7639288
TI  - Histiocytosis and two classes of M-proteinemia in pre-treated Ph positive ALL.

PMID- 7639287
TI  - Pharmacokinetics of meperidine in sickle cell patients.

PMID- 7639289
TI  - Long-term complete remission after interferon treatment in a case of multicentric
      Castelman's disease.

PMID- 7639290
TI  - Thrombocytopenia accompanying early postnatal infection by human parvovirus B19.

PMID- 7639291
TI  - Case of chronic B-lymphocytic leukemia with clover leaf nuclei.

PMID- 7639292
TI  - Cell adhesion receptors on neoplastic plasma cells.

PMID- 7639293
TI  - Congenital afibrinogenemia: successful prevention of recurrent hemoperitoneum
      during ovulation by oral contraceptive.

PMID- 7639294
TI  - ATRA-induced gingival infiltration: report of a case.

PMID- 7639295
TI  - Antiphospholipid antibodies and Sezary syndrome.

PMID- 7639296
TI  - Myasthenia gravis induced by alpha-interferon therapy.

PMID- 7639297
TI  - Anterior chamber contamination after uncomplicated phacoemulsification and
      intraocular lens implantation.
AB  - PURPOSE: To determine the frequency of anterior chamber contamination occurring
      during uncomplicated cataract surgery with intraocular lens implantation using
      phacoemulsification through a scleral tunnel incision. METHODS: In a prospective
      study, anterior chamber aspirates of one eye each of 103 consecutive ambulatory
      patients who underwent uncomplicated cataract surgery with lens implantation were
      cultured. The anterior chamber aspirate was withdrawn immediately upon the
      completion of surgery. Conjunctival cultures of the same eye were taken
      immediately before surgery, after the eye and periocular area had been prepared
      and draped. Multiple use topical medications used preoperatively on all patients
      were cultured at the end of the surgical day. RESULTS: Intraocular aspirates
      yielded positive cultures in five specimens (5%), four of which were identified
      as Staphylococcus epidermidis. Quantification disclosed colony counts ranging
      between 100 and 200 colony forming units per milliliter. Results of conjunctival
      cultures were positive in ten specimens (10%). Staphylococcus epidermidis was the
      most common isolate, identified in seven of the ten positive cultures. Positive
      intraocular and conjunctival culture results were not present concurrently in any
      patient. Microorganisms were recovered from the multiple use topical medications
      on nine of the 26 successive surgical days. Neisseria species was the most
      frequent isolate (7,44%), followed by S. epidermidis (5,31%). The frequency of
      contamination of the anterior chamber was independent of wound width (chi 2 =
      0.869) and operative time (chi 2 = 4.77). CONCLUSION: Bacterial contamination of
      the anterior chamber was detected in five (5%) of the patients. This reduced
      incidence of contamination compared with that of previous studies may be related
      to the preoperative preparation, the surgical technique, or both. Contamination
      of the multiple use topical medications and bulbar conjunctiva define possible
      sources of pathogens that may enter the anterior chamber. The absence of any
      clinical ocular infection in all patients attests to the small inoculum sizes, as
      well as the ability of the anterior chamber to clear small bacterial loads.

PMID- 7639298
TI  - A randomized trial comparing mitomycin C and conjunctival autograft after
      excision of primary pterygium.
AB  - PURPOSE: To determine the rate of recurrence and complications after bare sclera
      excision of primary pterygia followed by low-dose mitomycin C (0.2 mg/ml twice
      daily for five days), placebo (balanced saline solution), or conjunctival
      autograft. METHODS: We performed a prospective, double-masked clinical trial of
      64 patients (60 Hispanic) randomly assigned to a treatment group. Twenty-four
      patients received mitomycin C, 23 conjunctival autograft, and 17 placebo.
      Recurrence was defined as fibrovascular tissue over the corneoscleral limbus onto
      clear cornea in the area of previous pterygium excision. RESULTS: The recurrence
      rate after mitomycin C and conjunctival autograft was 38% and 39% of eyes,
      respectively, after mean follow-up (in recurrence-free patients) of 12.3 and 13.5
      months, respectively. The recurrence rate after placebo treatment was
      significantly higher (P = .002), 88%, after mean follow-up (in recurrence-free
      patients) of 9.3 months. Increasing age was associated with significantly fewer
      recurrences (P = .006) after controlling for pterygium type (atrophic,
      noninflamed, or inflamed) and treatment group. The mean time to recurrence varied
      from 3.7 to 4.8 months; only 6% of recurrences were noted after the sixth
      postoperative month. Major complications included symblepharon (two), loose
      autograft (one), and pyogenic granuloma (two). No group had significantly more
      complications. CONCLUSIONS: Conjunctival autograft and low-dose topical mitomycin
      C are equally effective as adjunctive treatment after excision of primary
      pterygia in this young, southern California, predominantly Hispanic population.
      Both methods have significantly lower rates of recurrence than bare sclera
      excision alone, and neither is associated with severe complications after one
      year of follow-up. Increasing patient age is associated with significantly less
      risk of recurrence.

PMID- 7639299
TI  - Echographic evaluation of primary cysts of the iris pigment epithelium.
AB  - PURPOSE: Primary cysts of the iris pigment epithelium frequently appear to be
      focal elevations of the peripheral iris. To differentiate them from other
      anterior segment tumors requires the ability to assess the distribution, tissue
      characteristics, and progression of such lesions, which we accomplished by using
      anterior segment echography. METHODS: We reviewed the medical records of 49
      consecutive patients referred to the Doheny Eye Institute for echographic
      evaluation of focal bulging of the peripheral iris. Echography of the anterior
      segment was performed on each patient by using an immersion technique. Clinical
      examination was also performed on 20 (41%) patients at the time of initial
      examination. RESULTS: We identified 52 iris pigment epithelial cysts in 52 eyes
      of the 49 patients studied. All lesions were single, localized to the posterior
      iris surface, and demonstrated a well-circumscribed, echolucent structure on B
      scan echography. Average maximal sagittal thickness was 1.6 +/- 0.4 mm. Cysts
      were most frequently located in the inferotemporal quadrant (31%). Minimal
      increase in size or regression of lesions was noted in the nine patients (ten
      eyes) for whom follow-up echographic examinations were available. CONCLUSIONS:
      Primary iris pigment epithelial cysts possess characteristic features with regard
      to location, size, and internal structure, which can be accurately documented
      with echography. Clinically evident lesions tend to be between 1 and 4 mm in
      maximum sagittal thickness, conform to the contour of posterior chamber
      structures without distortion, produce anterior bulging of the peripheral iris,
      are preferentially located in the inferotemporal quadrant, and demonstrate
      limited potential for growth.

PMID- 7639300
TI  - Retrobulbar arterial hemodynamic effects of betaxolol and timolol in normal
      tension glaucoma.
AB  - PURPOSE: beta-Adrenergic blocking drugs lower intraocular pressure. The question
      of whether these drugs also alter, either directly or indirectly, orbital
      hemodynamics is potentially of great importance for patients with normal-tension
      glaucoma who may have some degree of reversible vasospasm. METHODS: We compared
      the effect of selective (betaxolol) and nonselective (timolol) beta-adrenergic
      blocking drugs on flow velocities (as determined by color Doppler imaging) in
      orbital vessels in 13 patients with normal-tension glaucoma (mean age, 62 +/- 3
      years; mean intraocular pressure, 15 +/- 2 mm Hg). A one-month drug treatment
      double-masked crossover design, with a three-week washout before each drug, was
      used. RESULTS: Neither drug changed peak systolic velocity in any of the four
      vessels studied (ophthalmic, nasal and temporal posterior ciliary, and central
      retinal arteries). Additionally, timolol did not alter end-diastolic velocity or
      resistance index (defined as [peak systolic velocity minus end-diastolic
      velocity] divided by peak systolic velocity) in any of the vessels measured. In
      contrast, betaxolol tended to increase end-diastolic velocity and to decrease
      resistance index: the four-vessel average end-diastolic velocity increased 30% (P
      = .08), and the four-vessel average resistance index decreased significantly (P =
      .04). These reductions in resistance index occurred despite that betaxolol, in
      contrast to timolol, did not significantly decrease intraocular pressure.
      CONCLUSIONS: These results suggest that, in patients with normal-tension
      glaucoma, selective beta-adrenergic blockade (betaxolol) may have ocular
      vasorelaxant effects independent of any influence on intraocular pressure,
      whereas nonselective blockade (timolol) lowers intraocular pressure without
      apparently altering orbital hemodynamics.

PMID- 7639301
TI  - Comparison of clinician judgment with digitized image analysis in the detection
      of induced optic disk change in monkey eyes.
AB  - PURPOSE: To compare the ability of clinicians to detect change in the
      photographic appearance of the optic disk with the performance of a system for
      digitized image analysis. METHODS: In 11 monkey eyes, a Topcon Imagenet System
      was used to acquire eight digitized image pairs and four stereoscopic photographs
      at an intraocular pressure of 10 mm Hg, and then, again, 45 minutes after
      intraocular pressure was increased to 45 mm Hg. We recently reported detection of
      global (ten of 11 eyes) and regional (11 of 11 eyes) change in the digitized
      images of these eyes by using two new statistical strategies for optic disk
      analysis. For the current study, we evaluated the ability of three clinicians
      (the authors) to detect a change within the stereoscopic photographs of these 11
      optic disks. For each eye, the eight stereoscopic photographs (four at
      intraocular pressure of 10 mm Hg and four at intraocular pressure of 45 mm Hg)
      were developed as stereoscopic slides and arranged into four pairs (10/10, 45/45,
      10/45, and 45/10 mm Hg). Thus, two pairs represented no change in intraocular
      pressure (10/10 and 45/45 mm Hg) and the other two pairs represented either an
      increase or a decrease in intraocular pressure (10/45 and 45/10 mm Hg). The 44
      pairs of stereoscopic slides (four pairs for each of 11 eyes) were masked then
      randomly mixed. On two separate occasions, each clinician evaluated each pair of
      stereoscopic slides for the presence of absence of optic disk change. RESULTS:
      Reproducibility between the two readings of each clinician ranged from .50 to .64
      (kappa statistic). Clinicians correctly detected change (as detected by image
      analysis) within 45% to 64% of the 10/45 and 45/10 pairs of stereoscopic slides.
      Clinicians correctly indentified no change within 86% to 100% of the 10/10- and
      45/45-mm Hg pairs of stereoscopic slides. Clinicians correctly identified no
      change significantly more often than change (P < .01, chi 2 test). Change was not
      detected consistently by all three clinicians in any of the 11 eyes. CONCLUSION:
      In a controlled experimental setting, digitized image acquisition with extensive
      secondary statistical analysis more sensitively detected small short-term changes
      in the surface of the optic disks of monkeys than did three masked clinicians.

PMID- 7639302
TI  - Comparison of ganglion cell loss and cone loss in experimental glaucoma.
AB  - PURPOSE: To compare the loss of ganglion cells to cone loss in the macular area
      of monkey eyes with experimental glaucoma. METHODS: Experimental glaucoma was
      induced in eyes of three cynomolgus monkeys by argon laser applications to the
      trabecular meshwork. The average duration +/- S.D. of glaucoma in the
      experimental animals was 3.8 +/- 0.5 months. Glaucomatous damage was estimated,
      before the animals were killed, by evaluating stereoscopic photographs of the
      optic disk and red-free photographs of the nerve fiber layer. Ganglion cell
      nucleoli and cone pedicles were counted by using light microscopy from slides
      containing strips of retinal tissue. Cell density was then calculated by using
      the modified Abercrombie formula. Percent loss of ganglion cells and cones was
      determined from three eyes of three monkeys in 300-micron segments that were 900
      to 1,200 microns superior and inferior to the foveal center. RESULTS: Cone loss
      was not found at 4.5 to 6 degrees eccentricity above and below the fovea, whether
      damage was mild or severe. The average loss +/- S.D. of ganglion cells was 81.1%
      +/- 10.7%, whereas the average cone loss was only 3.5% +/- 6.4%. CONCLUSIONS:
      Marked parafoveal cone loss was not found in experimental glaucoma in which
      extensive damage to ganglion cells occurred.

PMID- 7639303
TI  - Alcohol use and age-related maculopathy in the Beaver Dam Eye Study.
AB  - PURPOSE: Because there are few epidemiologic data examining the relationship
      between alcohol use and age-related maculopathy, we investigated this
      relationship via the population-based Beaver Dam Eye Study. METHODS: Alcohol
      consumption in the year before examination was determined by a standardized
      questionnaire. Age-related maculopathy status was determined by grading
      stereoscopic color fundus photographs. RESULTS: While controlling for other
      factors, consumption of beer in the past year was related to greater odds of
      increased retinal pigment degeneration (odds ratio, 1.13; 95% confidence
      interval, 1.02, 1.25) and exudative macular degeneration (odds ratio, 1.41; 95%
      confidence interval, 1.05, 1.88). Current consumption of neither wine nor liquor
      was related to early or late age-related maculopathy. CONCLUSIONS: These data
      suggest a relationship between beer consumption and greater odds of having
      exudative macular degeneration. Whether this is from a toxic effect specific to
      beer or from other unknown confounders cannot be determined.

PMID- 7639304
TI  - Clinicopathologic correlation of surgically removed macular hole opercula.
AB  - PURPOSE: To determine the ultrastructural characteristic of the operculum
      associated with macular holes. METHODS: We developed instrumentation and a
      technique to capture the operculum observed with macular holes. Two opercula were
      studied by transmission electron microscopy. RESULTS: The two specimens were
      attached to a layer of native collagen identified as cortical vitreous and were
      composed primarily of Mueller cells and fibrous astrocytes without adjacent inner
      limiting membrane. No distinct retinal neuronal tissue was present. CONCLUSIONS:
      Our findings indicate that proliferation of fibrous astrocytes and Mueller cells
      occurs with the formation of a macular hole, that this reparative tissue may be
      dislodged, and it is the reparative tissue that previously has been interpreted
      as an operculum.

PMID- 7639305
TI  - Indocyanine green angiography in Stargardt's flavimaculatus.
AB  - PURPOSE: We studied the indocyanine green videoangiographic characteristics of
      eyes in patients with Stargardt's flavimaculatus and fluorescein angiographic
      evidence of a dark choroid. METHODS: Affected individuals underwent ophthalmic
      examination and fluorescein angiographic examination. Indocyanine green
      videoangiography was performed on eight patients with classic Stargardt's
      flavimaculatus. Two additional asymptomatic patients with mild manifestations of
      Stargardt's flavimaculatus, both of whom were related to one patient with the
      classic phenotype, were also examined with indocyanine green videoangiography.
      RESULTS: Choroidal detail was evident in all patients examined with indocyanine
      green videoangiography, and varying degrees of choroidal vascular closure were
      documented in the maculas of eight patients. Retinal pigment epithelial flecks
      were found to block indocyanine green videoangiographic fluoresence
      progressively. Late indocyanine green videoangiographic imaes frequently showed
      retinal pigment epithelial involvement in areas of retina thought to be
      uninvolved clinically and by fluorescein angiography. Peripapillary crescents of
      hypofluorescence, which in some patients were not noted clinically or by
      fluorescein angiography, were observed in all ten patients examined with
      indocyanine green videoangiography. In one asymptomatic patient, retinal pigment
      epithelial flecks could be identified only with indocyanine green
      videoangiography. CONCLUSIONS: Indocyanine green videoangiography in conjunction
      with fluorescein angiography can be a valuable tool in the recognition and
      further understanding of Stargardt's flavimaculatus.

PMID- 7639306
TI  - A sensitive and specific polymerase chain reaction-based assay for the diagnosis
      of cytomegalovirus retinitis.
AB  - PURPOSE: To develop a sensitive and specific laboratory assay for the diagnosis
      of cytomegalovirus retinitis. METHOD: We used a polymerase chain reaction-based
      assay for detection of cytomegalovirus DNA in vitreous samples. We attempted to
      detect cytomegalovirus DNA in 19 vitreous samples from patients with the acquired
      immunodeficiency syndrome (AIDS) who had untreated cytomegalovirus retinitis and
      in 40 vitreous samples from patients with AIDS who had been treated with systemic
      ganciclovir or foscarnet, or both. We also attempted to detect cytomegalovirus
      DNA in vitreous samples from 54 immunocompetent patients, including 32 with
      retinal detachment or macular hole, 11 with vitreous inflammation, and 11 with
      vitreous hemorrhage. Additionally, we attempted to detect cytomegalovirus DNA in
      15 vitreous samples from patients with AIDS who had vitreoretinal inflammation
      not caused by cytomegalovirus. RESULTS: Cytomegalovirus DNA was detected in 18 of
      19 eyes with untreated cytomegalovirus retinitis. We detected cytomegalovirus DNA
      in 19 of 40 vitreous samples from patients with previously treated
      cytomegalovirus retinitis. Cytomegalovirus DNA was not detected in any of 69
      patients who did not have a clinical diagnosis of cytomegalovirus retinitis.
      Thus, the assay had an estimated sensitivity of 95% in detecting untreated
      cytomegalovirus retinitis and a sensitivity of 48% in detecting cytomegalovirus
      retinitis that had been treated with systemic ganciclovir or foscarnet, or both.
      The assay did not give false-positive results in patients with vitreous
      hemorrhage or vitreous inflammation. Most important, the assay did not give false
      positive results in AIDS patients with vitreous inflammation from causes other
      than cytomegalovirus retinitis. CONCLUSION: We have developed a sensitive and
      specific diagnostic assay that will assist in the diagnosis of cytomegalovirus
      retinitis.

PMID- 7639307
TI  - Visual acuity modeling using optical raytracing of schematic eyes.
AB  - PURPOSE: We developed a methodology to predict changes in visual performance that
      result from changes in the optical properties of the eye. METHODS: Exact
      raytracing of schematic eyes was used to calculate the point spread function and
      the modulation transfer function of the visual system. The Stiles-Crawford
      effect, photopic response, diffraction, and the retinal contrast sensitivity are
      included in the model. Visual acuity was predicted by examining the modulation of
      the resultant retinal image of a bar target and by determining when the
      modulation falls below a threshold value. Visual acuity was predicted for
      refractive errors ranging from 0 to 5 diopters and for pupil diameters ranging
      from 0.5 to 8 mm. RESULTS: Visual acuity predictions were compared to clinically
      found Snellen visual acuities and were found to be highly correlated (r2 = .909).
      CONCLUSIONS: This modeling technique shows promise as a means of evaluating
      clinical and surgical procedures before undertaking clinical trails.

PMID- 7639308
TI  - Ophthalmologic findings in a patient with cerebellar ataxia, hypogonadotropic
      hypogonadism, and chorioretinal dystrophy.
AB  - PURPOSE: To determine the ophthalmologic findings in a 39-year-old woman with the
      Boucher-Neuhauser syndrome, which is a disorder of autosomal recessive
      inheritance characterized by the triad of spinocerebellar ataxia, chorioretinal
      dystrophy, and hypogonadotropic hypogonadism. METHODS: The patient underwent
      clinical and electrophysiologic examinations and fluorescein angiography.
      RESULTS: The main clinical findings were extensive areas of retinal pigment
      epithelial and choriocapillaris atrophy affecting the posterior pole and
      midperiphery of both eyes. Results of electroretinographic examination showed
      subnormal photopic and scotopic responses. CONCLUSIONS: The Boucher-Neuhauser
      syndrome should be included in the differential diagnosis of patients with
      chorioretinal degeneration, particularly if there are neurologic or
      endocrinologic manifestations.

PMID- 7639309
TI  - Macular pattern dystrophy associated with a mutation of mitochondrial DNA.
AB  - PURPOSE/METHODS: To establish association of a macular pattern dystrophy with
      maternally inherited diabetes and deafness, a new subtype of diabetes mellitus
      caused by a mutation of mitochondrial DNA (mtDNA). Two probands of two different
      families with maternally inherited diabetes and deafness were examined.
      RESULTS/CONCLUSION: Both probands exhibited a macular pattern dystrophy,
      maternally inherited in one patient. The association of a macular pattern
      dystrophy with diabetes should lead to screening for a mutation of mtDNA.

PMID- 7639310
TI  - Metastatic adenocarcinoma to the retina in a patient with Muir-Torre syndrome.
AB  - PURPOSE/METHODS: A 74-year-old woman had multiple tumors including a retinal
      mass. Her medical history included cutaneous sebaceous adenomas, adenocarcinoma
      of the breast, and colonic adenocarcinoma. Her involved eye became painful and
      was enucleated. RESULTS/CONCLUSIONS: Examination of the enucleated eye disclosed
      metastatic adenocarcinoma to the retina with retinal detachment. The patient
      described has a retinal metastasis of an unknown primary tumor site with Muir
      Torre syndrome, characterized by an association of a sebaceous gland tumor with
      an internal malignancy.

PMID- 7639311
TI  - Premacular hemorrhage as a sign of subacute bacterial endocarditis.
AB  - PURPOSE/METHODS: We examined a patient with mitral valve insufficiency, a sudden
      decrease in vision in the right eye, and premacular hemorrhage, which was a sign
      of subacute bacterial endocarditis. RESULTS/CONCLUSION: The patient was
      hospitalized and treated with intravenous antibiotics. Blood cultures grew
      Streptococcus viridans. Ocular symptoms and signs improved over two months.
      Premacular hemorrhage may be a sign of subacute bacterial endocarditis and may
      obscure other classic signs. Subacute bacterial endocarditis should be included
      in the differential diagnosis of premacular hemorrhage.

PMID- 7639312
TI  - Aqueous and vitreous humor samples for the diagnosis of cytomegalovirus
      retinitis.
AB  - PURPOSE/METHODS: Techniques for detection of viral DNA based on the polymerase
      chain reaction are increasingly being applied to ocular fluids; however, the
      clinical significance of such findings can sometimes be unclear. Two patients had
      the acquired immunodeficiency syndrome (AIDS) in whom different herpesviruses
      were detected in aqueous and vitreous fluids from the involved eye.
      RESULTS/CONCLUSIONS: In both patients dual viral infections were present and the
      application of polymerase chain reaction-based methods to ocular fluids made a
      useful contribution to the treatment of the patients.

PMID- 7639313
TI  - Induction of ligneous conjunctivitis by conjunctival surgery.
AB  - PURPOSE/METHODS: A woman with ligneous conjunctivitis of the left upper eyelid
      underwent conjunctival autograft transplant from the left lower to the upper
      eyelid. The disease in the upper eyelid persisted, and the previously healthy
      lower eyelid developed ligneous conjunctivitis at the autograft donor site.
      RESULTS/CONCLUSIONS: The conjunctivitis was aggressively treated with multiple
      surgical debridements and topical and oral medications, including topical
      cyclosporine. The conjunctivitis slowly resolved over the course of seven months,
      with the longest persistence in the upper eyelid at the junction between the
      original tissue and the autograft. We conclude that the conjunctival transplant
      surgery worsened ligneous conjunctivitis in this patient's upper eyelid and
      induced it in her lower eyelid.

PMID- 7639314
TI  - Aspergillus keratitis after radial keratotomy.
AB  - PURPOSE/METHODS: A case of severe Aspergillus keratitis after radial keratotomy
      manifested as a discrete midstromal infiltrate along a radial incision. Despite
      aggressive treatment with topical amphotericin B and oral itraconazole, the
      patient required a therapeutic penetrating keratoplasty. RESULTS/CONCLUSIONS:
      Histopathologic examination disclosed a corneal ulcer with numerous septate,
      branching hyphae throughout the stroma, and marked stromal necrosis. Aspergillus
      species should be included among the microbial pathogens responsible for
      infectious keratitis after radial keratotomy. If infectious keratitis is
      suspected, comprehensive cultures for bacteria and fungi should be obtained.

PMID- 7639315
TI  - Corneal abnormalities in a mother and daughter with focal dermal hypoplasia
      (Goltz-Gorlin syndrome).
AB  - PURPOSE/METHODS: Focal dermal hypoplasia is an inherited dermatologic disorder
      commonly associated with skeletal and dental abnormalities. Ocular abnormalities
      frequently found in patients with focal dermal hypoplasia include microphthalmos,
      anophthalmos, and colobomas. Corneal abnormalities rarely have been described in
      patients with focal dermal hypoplasia. We examined a mother and daughter with
      focal dermal hypoplasia with distinctive corneal lesions. RESULTS/CONCLUSION:
      Several discrete vascularized peripheral subepithelial corneal opacifications
      were present bilaterally in both patients with focal dermal hypoplasia. No ocular
      abnormalities that would predispose to these abnormalities were found. These
      corneal lesions appear to represent an unusual manifestation of focal dermal
      hypoplasia.

PMID- 7639316
TI  - Convergence insufficiency secondary to subdural hematoma.
AB  - PURPOSE/METHODS: Symptomatic convergence insufficiency developed in a 56-year-old
      man after he sustained head trauma and developed subdural hematoma.
      RESULTS/CONCLUSION: All symptoms resolved after surgical evacuation of the
      subdural hematoma. Convergence insufficiency developing after head trauma could
      be the result of a subdural hematoma.

PMID- 7639317
TI  - Simplified method of sizing implants for orbital fracture repair.
AB  - PURPOSE/METHODS: Over the past six years, we have used ordinary radiographic film
      as a template for sizing alloplastic implants for orbital fracture repair in over
      60 patients. The implants are made of such materials as titanium, Vitallium, and
      porous high-density polyethylene. Autoclaved 9.5 x 4.5-cm rectangles of
      radiographic film are easily trimmed, held by nontoothed forceps, inserted, and
      removed from the orbital cavity. RESULTS/CONCLUSIONS: We have found this simple
      and inexpensive technique to be superior to using aluminum templates that are
      supplied in commercially available plating sets.

PMID- 7639318
TI  - Orbital cellulitis, subperiosteal abscess, sinusitis, and septicemia caused b
      Arcanobacterium haemolyticum.
AB  - PURPOSE/METHODS: A 16-year-old boy had orbital cellulitis, subperiosteal abscess,
      sinusitis, and septicemia. Arcanobacterium haemolyticum was identified as the
      causative organism. RESULTS/CONCLUSIONS: This organism is a cause of orbital
      cellulitis and may require aggresive therapy in order to achieve a therapeutic
      response.

PMID- 7639319
TI  - Diagnosis and clinical characteristics of ocular Lyme borreliosis.

PMID- 7639320
TI  - Cataract in infants treated with argon laser photocoagulation for threshold
      retinopathy of prematurity.

PMID- 7639321
TI  - Death by any other name.

PMID- 7639322
TI  - Flavonoids: naturally occurring anti-inflammatory agents.

PMID- 7639323
TI  - Conformational mimicry in Alzheimer's disease. Role of apolipoproteins in
      amyloidogenesis.
AB  - Several apolipoproteins are known to be closely associated with amyloid
      fibrillogenesis. Serum amyloid A, apolipoprotein (apo) AII and apo A1 are each
      deposited as biochemically distinct forms of amyloid. Late-onset Alzheimer's
      disease is linked to one isotype of apo E, apo E4. Apo E and apo E4 in particular
      have been shown to modulate amyloid fibril formation by amyloid-beta peptides in
      vitro. Furthermore, the carboxy terminus of apo E has been shown to be a
      constituent of plaque amyloid. We show immunohistochemically and electron
      microscopically the presence of apo A1 in senile plaques. The intact apo A1 can
      itself form amyloid-like fibrils in vitro that are Congo Red positive. We propose
      that some proteins when misfolded can propagate this misfolding to identical
      units, either autocatalytically or to other proteins that are induced to fold
      into the same abnormal conformation. This conformational mimicry may initiate
      and/or augment fibrillogenesis in Alzheimer's disease.

PMID- 7639324
TI  - Coexpression of transforming growth factor-alpha and epidermal growth factor
      receptor in capillary hemangioblastomas of the central nervous system.
AB  - The expression of epidermal growth factor receptor (EGFR) and the pre-pro form of
      one of its ligands, transforming growth factor-alpha (TGF-alpha), was studied by
      Northern blotting in a series of 14 capillary hemangioblastomas of the central
      nervous system. A constant coexpression of EGFR and pre-pro-TGF-alpha mRNAs was
      found. Immunocytochemical investigation of an extended series of 51 capillary
      hemangioblastomas revealed that the stromal cells in these tumors showed
      immunoreactivity with monoclonal antibodies to EGFR and TGF-alpha. Analysis of
      gene dosage by Southern blotting in 20 tumors indicated a normal gene copy number
      of EGFR and TGF alpha in all cases. Our findings suggest that autocrine and/or
      juxtacrine growth stimulation via the EGFR may contribute to tumor growth in
      capillary hemangioblastomas.

PMID- 7639325
TI  - Evidence for apoptosis in advanced human atheroma. Colocalization with
      interleukin-1 beta-converting enzyme.
AB  - This study sought evidence for apoptosis, a form of programmed cell death, in
      human atheromatous coronary and carotid arteries. Markers for apoptotic cells
      included in situ terminal deoxynucleotidyl transferase-mediated dUTP nick end
      labeling (TUNEL), genomic DNA electrophoresis, and morphological analysis.
      Intimal lesions contained more TUNEL+ cells (34 +/- 6%, n = 8) than non
      atherosclerotic arterial intima (8 +/- 3%, n = 5, P < 0.05). The tunica media of
      the diseased arteries had a percentage of TUNEL+ cells (5 +/- 1%) similar to that
      in the normal vessels (3 +/- 1%, N.S.). Oligonucleosomal DNA fragments were
      visualized in extracts from 12 atheromatous plaques but in none of 5 non
      atherosclerotic vessels. Both smooth muscle cells (SMC) and macrophages, two
      major cell types in the atherosclerotic intima, bore markers of apoptosis, but
      with different patterns, as determined by double histochemical labeling for cell
      types and TUNEL. The TUNEL+ SMC localized mainly in the fibrotic portion of the
      atheroma, whereas TUNEL+ macrophages clustered near or within the lipid-rich core
      of the lesion. Atheromatous lesions expressed mRNA encoding interleukin-1 beta
      converting enzyme (ICE), a mammalian cell death gene, as demonstrated by reverse
      transcriptase polymerase chain reaction. Immunohistochemistry revealed that ICE
      localized in regions of TUNEL+ SMC and macrophages. TUNEL- cells showed little or
      no immunoreactive ICE. These data point to a role for apoptosis in regulation of
      cell accumulation during atherogenesis and suggest involvement of ICE in SMC
      death in fibrous regions of complex atheroma, and in macrophage death in the
      lipid-rich core of the lesion. Apoptosis of vascular cells in fibrous cap may
      impede maintenance or repair of the matrix in this region and affect stability of
      the plaques.

PMID- 7639326
TI  - Evidence for apoptosis in human atherogenesis and in a rat vascular injury model.
AB  - Apoptosis is a physiological cell death process important for normal development
      and involved in many pathological conditions. In atherosclerosis, pathological
      accumulation of cells in the intima has been attributed to the migration and
      proliferation of smooth muscle cells, macrophages, and lymphocytes. In this
      report, we explored the possibility that apoptosis may also contribute to the
      pathogenesis of this disease. We examined 35 human atherosclerotic lesion samples
      and identified a substantial number of cells undergoing apoptosis in 25 of the
      samples. Furthermore, in a rat vascular injury model, apoptotic cells were
      specifically identified in the neointima. The presence of apoptotic cells was
      demonstrated by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick
      end labeling, nuclear staining with propidium iodide, and electron microscopy.
      Immunostaining with cell-type-specific markers and subsequent terminal
      deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling analysis on
      the same sample revealed that the majority of the apoptotic cells were modulated
      smooth muscle cells as well as macrophages. These results indicate that apoptosis
      occurs in cells of the injured blood vessel as well as the advanced
      atherosclerotic lesion and that physiological cell death may have an important
      role in determining the course of atherogenesis.

PMID- 7639327
TI  - Prominence of coronary arterial wall lipids in human heart allografts.
      Implications for pathogenesis of allograft arteriopathy.
AB  - Transplant arteriopathy is a major late complication in human heart allograft
      recipients and the pathogenesis of such arteriopathy remains uncertain. The
      degree to which lipids and atheromata are involved in the arteriopathic lesions
      remains unsettled, and there is uncertainty regarding the significance of
      insudation or retention of lipids within the coronary artery walls of
      transplanted hearts. On current immunosuppressive regimens, most patients
      experience an increased serum total cholesterol and low-density lipoprotein
      cholesterol after transplant. Elevation of these blood lipids has an undetermined
      relationship to arteriopathy. We carried out morphological, morphometric,
      immunohistochemical, ultrastructural, and biochemical studies of particular
      coronary artery segments from 23 unselected explant or autopsy allografts and
      donor age-matched native coronary controls. Patients died of cardiac and non
      cardiac reasons over a period of 4 to 1610 days after transplant. Atheromata were
      frequent, and diffuse intra- and extra-cellular accumulation of lipids in both
      intimal and medial walls was documented by oil red O positivity,
      immunohistochemical staining (muscle-specific alpha-actin), transmission and
      scanning electron microscopy, and biochemical analysis. Mean total cholesterol,
      esterified cholesterol, free cholesterol, and phospholipid content (microgram/cm2
      intimal surface area) and concentration (microgram/mg dry defatted weight) in
      arteriopathic coronaries were > 10-fold higher than in comparable native coronary
      segments. Extent of lipids in the arterial walls was highly correlated with
      digitized percent luminal narrowing, mean daily and cumulative cyclosporin dose,
      and mean cumulative prednisone dose. Our data suggests strongly that lipid
      accumulation is an important early and persistent phenomenon in the development
      of transplant arteriopathy.

PMID- 7639328
TI  - Neurotrophin and neurotrophin receptors in vascular smooth muscle cells.
      Regulation of expression in response to injury.
AB  - The neurotrophins, a family of related polypeptide growth factors including nerve
      growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin
      (NT)-3 and NT-4/5 promote the survival and differentiation of distinctive sets of
      embryonic neurons. Here we define a new functional role for neurotrophins, as
      autocrine or local paracrine mediators of vascular smooth muscle cell migration.
      We have identified neurotrophins, and their cognate receptors, the trk tyrosine
      kinases, in human and rat vascular smooth muscle cells in vivo. In vitro,
      cultured human smooth muscle cells express BDNF; NT-3; and trk A, B, and C.
      Similarly, rat smooth muscle cells expressed all three trk receptors as well as
      all four neurotrophins. Moreover, NGF induces cultured human smooth muscle cell
      migration at subnanomolar concentrations. In the rat aortic balloon
      deendothelialization model of vascular injury, the expression of NGF, BNDF, and
      their receptors trk A and trk B increased dramatically in the area of injury
      within 3 days and persisted during the formation of the neointima. In human
      coronary atherosclerotic lesions, BDNF, NT-3, and NT-4/5, and the trk B and trk C
      receptors could be demonstrated in smooth muscle cells. These findings suggest
      that neurotrophins play an important role in regulating the response of vascular
      smooth muscle cells to injury.

PMID- 7639329
TI  - Collagen remodeling after myocardial infarction in the rat heart.
AB  - In this study changes in the amount and distribution of types I and III collagen
      mRNA and protein were investigated in the rat heart after induction of a left
      ventricular myocardial infarction (MI). Sham operated rats served as controls.
      The animals were sacrificed at different time intervals after operation. Northern
      blotting of cardiac RNA and hybridization with cDNA probes for types I and III
      procollagen revealed a 5- to 15-fold increase in the infarcted left ventricle.
      Type III procollagen mRNA levels were already increased at day 2 after MI,
      whereas type I procollagen mRNA followed this response at day 4 after MI. This
      increase was sustained for at least 21 days in the infarcted left ventricle for
      type III procollagen mRNA, whereas type 1 procollagen mRNA levels were still
      elevated at 90 days after MI. In the noninfarcted right ventricle a 5- to 7-fold
      increase was observed for both type I and type III procollagen mRNA levels, but
      only at day 4 after MI. In the non-infarcted septum a transient increase was
      observed for type I procollagen mRNA from day 7-21 (4- to 5-fold increase) and a
      decline to sham levels thereafter. In the septum type III procollagen mRNA levels
      were only elevated at 7 days after MI (4- to 5-fold increase) compared with sham
      operated controls. In situ hybridization with the same types I and III
      procollagen probes showed procollagen mRNA-producing cells in the infarcted area
      around necrotic cardiomyocytes, and in the interstitial cells in the non
      infarcted part of the myocardium. No labeling was detected above cardiomyocytes.
      Combined in situ hybridization and immunohistochemistry showed that the collagen
      mRNA producing cells have a myofibroblast-like phenotype in the infarcted
      myocardium and are fibroblasts in the noninfarcted septum and right ventricle.
      The increase in types I and III procollagen mRNA in both infarcted and non
      infarcted myocardium was followed by an increased collagen deposition, measured
      by computerized morphometry on sirius red-stained tissue sections as well as by
      the hydroxyproline assay. In the non-infarcted septum and right ventricle the
      collagen-positive area was maximal at day 14 (3- to 5-fold increase compared with
      sham operated controls) and slightly declined at day 21. In the infarcted
      myocardium the collagen-positive area was 57 +/- 10% at day 14 after MI.
      Hydroxyproline contents were significantly increased in the noninfarcted
      septum.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7639330
TI  - Elevated D-glucose concentrations modulate TGF-beta 1 synthesis by human cultured
      renal proximal tubular cells. The permissive role of platelet-derived growth
      factor.
AB  - Interstitial fibrosis is a marker of progression of renal impairment in diabetic
      nephropathy. Transforming growth factor (TGF)-beta 1 is one of a group of pro
      fibrotic cytokines and growth factors that have been associated with the
      development of interstitial fibrosis. We have examined the modulating influence
      of glucose on the production of TGF-beta 1 by cultured human proximal tubular
      cells. Incubation of growth-arrested human proximal tubular cells (HPTC) (72
      hours in serum free medium) in 25 mmol/L D-glucose resulted in increased
      expression of TGF-beta 1 mRNA (as assessed by reverse transcription polymerase
      chain reaction). This was apparent after 6 hours and increased up to 120 hours
      exposure. TGF-beta 1 secretion, however, as measured by specific enzyme-linked
      immunoassay, was unaffected by exposure to 25 mmol/L D-glucose. Sequential
      stimulation of HPTC, first with 25 mmol/L D-glucose for 48 hours and then with
      platelet-derived growth factor (PDGF) isoforms, resulted in a dose-dependent
      secretion of TGF-beta 1. Pre-exposure to 5 mmol/L D-glucose or 25 mmol/L L
      glucose did not prime for TGF-beta 1 release. At 50 ng/ml PDGF this effect was
      greatest for the AA isoform (AA 31.4 +/- 7.1, AB 20.98 +/- 8.9, BB 7.8 +/- 2.2, P
      < 0.05 for all versus control, n = 3, mean +/- SEM ng/10(6) cells/24 hours).
      These effects were blocked by the addition of antibody to the PDGF alpha
      receptor. TGF-beta 1 secretion was inhibited in a dose-dependent manner by
      pretreatment with cyclohexamide, but was not affected by pretreatment with
      actinomycin D. Stimulation of HPTC with a single dose of PDGF induced TGF-beta 1
      mRNA; however, only after application of a second dose of PDGF (after TGF-beta 1
      mRNA induction) did TGF-beta 1 protein secretion occur. We also demonstrated that
      PDGF stimulation of HPTC induced an inherently more stable TGF-beta 1 mRNA
      transcript. These findings demonstrate that elevated D-glucose concentration
      alone is insufficient to lead to increased TGF-beta 1 secretion by HPTC despite
      increased mRNA expression. However, application of a second stimulus such as
      PDGF, when TGF-beta 1 mRNA expression is increased, leads to increased protein
      synthesis and secretion of TGF-beta 1. This implies that elevated glucose
      concentrations might prime proximal tubular cells for TGF-beta 1 synthesis and
      thus contribute to the development of interstitial fibrosis.

PMID- 7639331
TI  - Pathogenesis of glomerulosclerosis in light chain deposition disease. Role for
      transforming growth factor-beta.
AB  - The glomerulopathy of monoclonal immunoglobulin light chain deposition disease is
      a progressive disorder characterized by accumulation of monoclonal light chains
      and matrix proteins in the mesangium. To define the role of light chains in this
      process, cultured rat mesangial cells were exposed to different light chains and
      human albumin. Two light chains were purified from the urine of patients who had
      biopsy-proven light chain deposition disease. These proteins inhibited mesangial
      cell proliferation and increased production of matrix proteins, including type IV
      collagen, laminin, and fibronectin. By immunocytochemistry and bioassay,
      transforming growth factor-beta (TGF-beta) production and activity increased when
      mesangial cells were exposed to these proteins. Furthermore, anti-TGF-beta
      antibody abolished the inhibition of cell proliferation and the increase of
      extracellular matrix protein production caused by these light chains. These
      findings were not observed in mesangial cells exposed to human albumin and two
      other light chains previously characterized to be tubulopathic. We concluded that
      the glomerulopathic light chains increased TGF-beta, which inhibited mesangial
      cell proliferation and increased matrix protein production. Together with
      overexpression of TGF-beta in affected glomeruli of light chain deposition
      disease, light chain-mediated stimulation of mesangial cells to produce TGF-beta
      appears to be a key pathological mechanism of this disease.

PMID- 7639332
TI  - Hepatocyte growth factor and its receptor (c-MET) in prostatic carcinoma.
AB  - Hepatocyte growth factor (scatter factor) and its receptor, the c-met proto
      oncogene product (c-MET), have been implicated in embryogenesis, tissue
      reorganization, and tumor progression. Little is known, however, of the
      expression and functional significance of these molecules in prostatic cells and
      tissue. In this investigation, we assessed the expression of hepatocyte growth
      factor (HGF) and c-MET in prostatic tissues and cell lines and also determined
      the effect of purified recombinant HGF on cell proliferation and scattering of
      prostatic carcinoma cell lines. HGF was expressed by human prostatic stromal
      myofibroblasts in primary culture but not by three human prostatic carcinoma cell
      lines (LNCaP, DU 145, and PC-3) as assessed by Northern blot analysis. HGF was
      also detected by reverse transcriptase-polymerase chain reaction in both benign
      and malignant tissues from radical prostatectomy specimens. c-MET transcripts
      were identified by Northern blot in two androgen-insensitive human prostatic
      carcinoma cell lines (DU 145 and PC-3) but not the androgen-sensitive LNCaP cell
      line. Additional evidence of linkage of androgen responsiveness and c-MET was
      provided by experiments in which androgen deprivation of normal rat prostates via
      castration produced a marked up-regulation of c-MET expression as determined by
      Northern blot and immunohistochemistry. c-MET protein was detected by
      immunohistochemical analysis in a substantial percentage (58 of 128 or 45%) of
      prostatic carcinomas and was found more often in metastatic growths of human
      prostatic carcinoma (15 of 20 patients) compared with primary tumors (43 of 108
      patients; P < 0.005). Moreover, in Dunning R-3327 rat prostatic carcinoma cell
      lines, c-MET expression was highest in the androgen-insensitive subline with the
      highest metastatic capacity. Purified recombinant human HGF induced dose
      dependent cellular proliferation and scattering in the DU 145 carcinoma cell
      line. These data indicate that HGF may function in the prostate gland as a
      paracrine growth factor, with synthesis by stromal cells and with biological
      target cells being the epithelial cells. Expression of the HGF receptor, c-MET,
      is up-regulated by androgen deprivation and c-MET appears to be preferentially
      expressed on androgen-insensitive, metastatic cells, suggesting a possible
      linkage of c-MET expression with prostatic carcinoma progression.

PMID- 7639333
TI  - Morphometric and immunohistochemical characterization of human liver
      regeneration.
AB  - Regeneration in human liver is characterized in part by the formation of ductular
      structures, so-called ductular hepatocytes in massive hepatic necrosis and bile
      ductules in mechanical biliary obstruction. In an attempt to characterize the
      liver regenerative process, we performed image analysis and immunohistochemical
      staining of the ductular structures in these well defined human liver disorders,
      13 cases of massive hepatic necrosis and 9 cases of mechanical biliary
      obstruction. The proliferation index was determined and the expression of several
      antigens was localized by immunohistochemical staining using antibodies to alpha
      fetoprotein, alpha-1-antitrypsin, albumin, and cytokeratin 19. The ductular
      structures in adult human liver were compared with the developing ductal plates
      in 11 fetal livers, ranging in age from 9 to 36 weeks of gestation. Image
      analysis demonstrated that the mean total area, mean nuclear area, and mean cell
      size of ductular hepatocytes were significantly larger than those of bile
      ductules (p < 0.05). The proliferation index of ductular hepatocytes and bile
      ductules was significantly higher than that of hepatocytes of normal livers (p <
      0.02). Bile ducts, bile ductules in mechanical biliary obstruction, ductular
      hepatocytes in massive hepatic necrosis, and the ductal plate cells in fetal
      liver showed strong staining for cytokeratin 19, which characterizes intermediate
      filaments associated with bile duct epithelial cells. Albumin, a liver-specific
      protein, and alpha-1-antitrypsin, a protease inhibitor, were strongly expressed
      in ductal plate cells of fetal liver, hepatocytes, and ductular hepatocytes,
      whereas bile duct cells and bile ductules were negative for albumin. In summary,
      ductular hepatocytes demonstrate morphometric and immunophenotypic features of
      both hepatocytes and biliary epithelial cells, whereas bile ductules share
      characteristics primarily with fetal ductal plates and mature bile ducts. These
      findings suggest that ductular hepatocytes in massive hepatic necrosis may serve
      as bipotential progenitor cells, and bile ductules in mechanical biliary
      obstruction are related to ductal plates of fetal liver.

PMID- 7639334
TI  - A specific monoclonal antibody (PG-B6) detects expression of the BCL-6 protein in
      germinal center B cells.
AB  - The BCL-6 gene is frequently involved in translocations occurring at the 3q27
      locus and is rearranged in approximately 30% of diffuse large cell lymphomas and
      in a small fraction of follicular lymphomas. The BCL-6 gene encodes for a Kruppel
      type zinc-finger protein, the cell/tissue expression and function of which is
      unknown. In this study, we describe a new monoclonal antibody (PG-B6) that is
      specifically directed against a fixative-sensitive epitope on the amino-terminal
      region of the BCL-6 protein. By immunocytochemical analysis, BCL-6 localizes in
      the nucleus where PG-B6 staining gives a microgranular/diffuse pattern with
      exclusion of the nucleoli. The main reactivity of PG-B6 in tonsil and spleen is
      with the nuclei of germinal center B cells, whereas B cells within the mantle and
      marginal zones do not express BCL-6. No other lymphoid cells in the tonsil
      express BCL-6 except for a subset of CD3+/CD4+ intrafollicular and
      interfollicular T cells. A few lymphoid cells of unknown phenotype express BCL-6
      in the thymus. Extra-lymphoid BCL-6 expression includes a weak nuclear positivity
      of epithelia. In non-Hodgkin's lymphomas, BCL-6 expression parallels that
      observed in normal lymphoid compartments, eg, expression in germinal center
      derived tumors (follicular and diffuse large cell lymphomas), but not in mantle
      cell and marginal zone lymphomas. In most diffuse large cell lymphomas, the BCL-6
      protein is expressed at high levels in cases with or without BCL-6 gene
      rearrangements. These findings indicate that BCL-6 expression is specifically
      regulated during B lymphocyte development and suggest that BCL-6 may play a role
      during B cell differentiation in the germinal center.

PMID- 7639335
TI  - The Emu-bcl-2 transgene enhances antigen-induced germinal center formation in
      both BALB/c and SJL mice but causes age-dependent germinal center hyperplasia
      only in the lymphoma-prone SJL strain.
AB  - Emu-bcl-2 transgenic and littermate control BALB/c and SJL mice were immunized in
      the front footpads with trinitrophenylated Brucella abortus and the germinal
      center (GC) response in draining brachial lymph nodes was studied by staining
      with peanut agglutinin peroxidase and methyl green. Although the GCs induced were
      not larger in transgenic than in control young mice, there was a significant
      increase in the percentage of B cell follicles exhibiting GCs 7 to 8 days after
      primary and secondary antigen injections in the transgenic mice of both strains.
      In addition, glucocorticosteroid injected on day 7 after the primary injection
      caused a marked decrease in GCs in littermate controls but had no effect in the
      bcl-2 transgenic SJL mice. Antibody production to B. abortus was only slightly
      higher in transgenic than in control mice, but anti-TNP immunoglobulin M and G
      titers were significantly enhanced in the transgenic mice. The bcl-2 transgenic
      SJL mice, older than 6 months, showed the spontaneous appearance of large numbers
      of peanut agglutinin-binding GCs that greatly varied in size and were located
      without regard for the normal lymph node structure or follicle localization. This
      GC hyperplasia was seen in a large percent of the older transgenic SJL mice and
      never in similarly aged normal SJL or BALB/c mice with and without the bcl-2
      transgene. Frank lymphomatous transformation of peanut agglutinin-binding
      germinal center-like areas was seen in lymph nodes and Peyer's patches of some of
      the older bcl-2 transgenic SJL mice. These results suggest that the tendency of
      SJL mice to develop GC-derived lymphomas synergizes with the presence of the bcl
      2 transgene to cause the development of GC hyperplasia.

PMID- 7639336
TI  - Spontaneous apoptosis in human thymocytes.
AB  - Apoptosis seems to be involved in different stages of immune cell development. In
      particular, experimental evidence suggests that it is a major form of cell death
      in the thymus. The present analysis of human thymocytes reveals that a fraction
      of these cells, cultured in vitro, undergoes spontaneous apoptosis. This
      observation is based both on molecular (DNA fragmentation) and morphological
      (electron microscopic) investigations of the cells. The apoptotic thymocytes are
      CD3- or CD3lo, CD4lo, and CD8lo and do not express Bcl-2 protein. Furthermore,
      thymocytes die by apoptosis when exposed to pharmacological stimuli, such as
      tumor necrosis factor-alpha, dexamethasone, ATP, or Ca++ ionophore. Thus the
      apoptotic machinery in thymocytes can be triggered by an imbalance in growth
      factors in the in vitro culture media and can be modulated by various biochemical
      signals. The process of spontaneous apoptosis is independent of mRNA or protein
      synthesis, as actinomycin D and cycloheximide fail to inhibit this phenomenon.
      Furthermore, apoptosis seems to require active oxidative phosphorylation, as it
      is prevented by incubation of the cells with inhibitors of the respiratory chain.

PMID- 7639337
TI  - Local and systemic response of mice to interferon-alpha 1-transfected Friend
      leukemia cells.
AB  - DBA/2 mice were injected subcutaneously with an interferon (IFN)-alpha/beta
      resistant line of Friend erythroleukemia cells (FLC) transfected with the mouse
      IFN-alpha 1 gene. These tumor cells produced IFN constitutively, and mice had
      persistently high levels of IFN in the circulation. We examined the IFN-induced
      host mechanisms responsible for the local inhibition of growth of these IFN-alpha
      transfected FLC and some of the unusual systemic effects of constant
      interferonemia such as extramedullary hematopoiesis in the liver, an increase in
      myeloid cells in the spleen, and persistently elevated splenic natural killer
      (NK) cell activity. In addition, both DBA/2 +/bg and beige mice developed a rapid
      and specific resistance to intravenous challenge with parental FLC. In previous
      experiments DBA/2 beige mice could not be protected by exogenous IFN-alpha/beta.
      The differences in the response of mice to the constitutive production of IFN
      alpha by IFN-alpha-transfected tumor cells and their response to exogenous IFN is
      discussed in terms of the effects of IFN on the host and of antitumor therapy.

PMID- 7639339
TI  - Topographic abnormalities of proinsulin to insulin conversion in functioning
      human insulinomas. Comparison of immunoelectron microscopic and clinical data.
AB  - It has been proposed that the major defect in human insulinomas is a decreased
      hormone storage capacity resulting in uncontrolled release of proinsulin and
      insulin. By immunoelectron microscopy with monoclonal antibodies we studied the
      subcellular distribution of proinsulin and insulin in benign and malignant
      functioning insulinomas of different histology and compared the findings with
      various clinical and pathohistological parameters. We found that, in contrast to
      normal B cells, the proinsulin to insulin conversion in insulinomas occurs
      already in the trans Golgi apparatus but remains incomplete, resulting in the
      formation of secretory granules containing both proinsulin and insulin. Thus, in
      functioning insulinomas, sorting into secretory granules is not a prerequisite
      for hormone conversion. Furthermore, proinsulin and insulin storage and most
      probably subsequent secretion occurs through the secretory granules via the
      regulated pathway. A substantial variability for both proinsulin and insulin
      immunolabeling in secretory granules was found not only in individual tumor cells
      but also among the insulinomas studied. This observed variability may account for
      the lack of correlation between pathohistological, immunohistochemical, and
      clinical parameters in functioning insulinomas.

PMID- 7639338
TI  - Infrequency of cytomegalovirus genome in coronary arteriopathy of human heart
      allografts.
AB  - In heart transplantation, long-term engraftment success is severely limited by
      the rapid development of obliterative disease of the coronary arteries. Data from
      various groups have been suggestive of a pathogenetic role of herpesviruses,
      particularly human cytomegalovirus, in accelerated allograft coronary artery
      disease; however, results are not yet conclusive. This study examines the
      hypothesis that human cytomegalovirus infection of allograft tissues is related
      pathogenetically and directly to accelerated coronary artery disease. Using in
      situ DNA hybridization and polymerase chain reaction, we examined particular
      coronary artery segments from 41 human heart allografts (ranging from 4 days to
      greater than 4 years after transplantation; mean, 457 days) and 22 donor age- and
      gender-comparable, coronary site-matched trauma victims for presence of human
      cytomegalovirus DNA. Human cytomegalovirus genome was detected in 8 of 41 (19.5%)
      allografts and in 1 of 22 (4.5%) control hearts. This difference in positivity
      was not statistically significant (P = 0.10). In the human cytomegalovirus
      positive hearts, viral genome was localized to perivascular myocardium or
      coronary artery media or adventitia. Human cytomegalovirus genome was not
      detected in arterial intima of any allograft or control heart, although human
      cytomegalovirus genome was readily identified within intima of small pulmonary
      arteries from lung tissue with human cytomegalovirus pneumonitis. By statistical
      analyses, the presence of human cytomegalovirus genome was not associated with
      the nature or digitized extent of transplant arteriopathy, evidence of rejection,
      allograft recipient or donor serological data suggestive of human cytomegalovirus
      infection, duration of allograft implantation, or causes of death or
      retransplantation. Thus, our data indicate a low frequency of detectable human
      cytomegalovirus genome in accelerated coronary artery disease and do not support
      a direct role for human cytomegalovirus in vascular wall infection or in the
      development of accelerated coronary artery disease.

PMID- 7639340
TI  - Chemical and immunological heterogeneity of fibrillar amyloid in plaques of
      Alzheimer's disease and Down's syndrome brains revealed by confocal microscopy.
AB  - Amyloid beta peptides (A beta) are deposited in the brains of Alzheimer's disease
      (AD) and elderly Down's syndrome (DS) patients in a variety of amyloid plaques.
      Among these are classical plaques composed of a spherical core and corona.
      Analyzing AD tissue sections single and double stained with anti-A beta
      antibodies and thioflavin S (thioS) by bright field, fluorescence, and confocal
      microscopy revealed that spherical plaque cores consist of a thioS-positive
      center and an anti-A beta antibody immunoreactive rim. This indicates that there
      is a fibrillar form of amyloid that is thioS positive but not immunoreactive with
      anti-A beta antibodies. In contrast, classical plaques in DS patients have
      irregular cores that are thioS positive as well as anti-A beta immunoreactive. In
      addition, a subset of plaques in both DS and AD patients have a distinct
      "fibrous" appearance when stained with thioS, but are amorphous when
      immunostained. These findings suggest that anti-A beta antibodies and thioS stain
      similar; as well as different forms of fibrillar amyloid. A beta may become thioS
      positive by interacting with one or more of its known molecular chaperons, and
      this may be important for the pathogenesis of AD, given that thioS-positive A
      beta deposits are associated with neuritic and synaptic damage.

PMID- 7639341
TI  - Atomic force microscopy of paired helical filaments isolated from the autopsied
      brains of patients with Alzheimer's disease and immunolabeled against microtubule
      associated protein tau.
AB  - Atomic force microscopy was employed to study the structural features of paired
      helical filaments isolated from autopsied brains of Alzheimer's disease patients.
      The identity of paired helical filaments was confirmed following a specific
      immunogold labeling using antibodies directed against the microtubule-associated
      protein tau, which is the main constituent of paired helical filaments. Computer
      assisted analysis of high resolution, three-dimensional images allowed us to
      study the longitudinal and cross-sectional profiles of individual filaments.
      Vertical dimensions of filaments were assessed along these sectional profiles.
      The smallest vertical diameter (6.66 +/- 0.78 nm) was obtained at the level of
      the greatest lateral profile (ie, "loop"), while the greatest vertical diameter
      was two times larger (13.68 +/- 1.46 nm) and was obtained at the level of the
      smallest lateral profile (ie, "crossover") of the filament. Based on the shapes
      of these sectional profiles and their vertical dimensions, paired helical
      filaments appeared to be composed of two identical integral subunits, each of a
      circular cross-sectional profile of approximately 7 nm in diameter, wound around
      one another in a left helical manner, with a 7-nm center-to-center separation.
      Half-period of this helix was estimated at 81.4 +/- 2.1 nm. Serial cross
      sectional profiles of paired helical filaments were further utilized to construct
      a theoretical model of their internal organization. This model suggests that each
      structural subunit of the paired helical filament incorporates at least four
      identical protofilaments.

PMID- 7639342
TI  - Excretion of alpha-tocopherol into human seminal plasma after oral
      administration.
AB  - In this open controlled study, we investigated the blood and seminal plasma
      concentrations of alpha-tocopherol in 15 unselected male volunteers, who received
      either 600, 800 or 1200 mg d-alpha-tocopherol per day for 3 weeks. During the
      intervention, both the blood and seminal plasma vitamin E concentrations
      increased significantly, although the increase did not correlate with the dose
      administered. The highest median blood and seminal plasma concentrations were
      achieved with 800 mg vitamin E per day, but the differences between the group
      medians were not significant, except in the blood plasma concentration after the
      first week of treatment between men receiving 600 and 800 mg per day (P < 0.05).
      No significant improvement was noted in the movement characteristics of
      spermatozoa, hypo-osmolar swelling of spermatozoa, or the velocity of
      deterioration in the parameters mentioned above. The seminal plasma vitamin E
      concentrations achieved during the treatment remained low (< 1 mumol l-1)
      compared to the concentrations found effective in protecting spermatozoa from
      peroxidative damage in vitro.

PMID- 7639343
TI  - Seminal fibronectin-like antigen and transferrin concentrations in infertile and
      fertile men.
AB  - Fibronectin like antigen (Fn) and transferrin (Trs) levels were measured in the
      seminal plasma of 40 fertile and 102 infertile men. The concentrations of both
      proteins were significantly (P < 0.001) higher in the fertile controls compared
      to the infertile groups. The levels of Fn and Trs (mean value +/- SEM) in the
      fertile men were 857.9 +/- 9.8 micrograms ml-1 and 164.0 +/- 6.5 micrograms ml-1,
      respectively; in the azoospermic men (n = 17) 552.7 +/- 24.65 micrograms ml-1 and
      20.7 +/- 2.19 micrograms ml-1, respectively; in the group of severe
      oligozoospermia (n = 35) 568.34 +/- 25.7 micrograms ml-1 and 31.1 +/- 4.18
      micrograms ml-1, respectively; in the moderate oligozoospermic group (n = 8)
      572.50 +/- 47.9 micrograms ml-1 and 43.4 +/- 15.4 micrograms ml-1 respectively,
      and in the asthenozoospermic group (n = 26) 512.76 +/- 40.4 micrograms ml-1 and
      47.0 +/- 7.9 micrograms ml-1, respectively. Of special interest was the finding
      from a group of 16 normospermic men (partners of couples with unexplained
      infertility) who showed significantly lower levels of Fn like antigen, 632.5 +/-
      26.9 micrograms ml-1 (P < 0.001) and Trs 41.8 +/- 6.94 micrograms ml-1 (P <
      0.0001) compared to normals. No correlation was found between Fn levels with
      either Trs or FSH levels or sperm count. In conclusion, our results indicate that
      male infertility is associated with changes in seminal plasma Fn like antigen
      concentrations and that it can be possibly used as an index of sperm fertilizing
      capacity.

PMID- 7639344
TI  - Value of sperm morphology assessed by strict criteria for prediction of the
      outcome of artificial (intrauterine) insemination.
AB  - The purpose of this study was to investigate the relationship between sperm
      parameters and the outcome of artificial (intrauterine) insemination (IUI). One
      hundred and twenty-six patients undergoing 395 consecutive IUI cycles in a 1-year
      period in our institution were studied. In all cases, controlled ovarian
      stimulation and hCG-timed IUI were performed, followed by progesterone
      supplementation of the luteal phase. In 86 patients, (243 cycles) the husband's
      sperm was utilized, whereas in 40 couples (152 cycles), donor sperm was used due
      to severe male factor infertility. Among the sperm parameters of the original
      ejaculate, % normal morphology (assessed by strict criteria) was the most
      significant predictor of pregnancy (stepwise regression analysis, P = 0.003).
      Using logistic regression, morphology was the best predictor of pregnancy (r =
      0.12); linearity of movement significantly enhanced the predictive value of
      morphology alone (r = 0.17, P = 0.004). Overall, the pregnancy rates were
      significantly higher (P = 0.01) in cases with > or = 14% normal morphology (15%
      per cycle) compared to cases with < 14% normal morphology (7% per cycle). This
      threshold level for morphology is in agreement with previously published IVF
      results. These results underscore the significance of sperm morphology assessed
      by strict criteria as a predictor of pregnancy outcome in the IUI setting.

PMID- 7639345
TI  - Choosing among different technical variations of Percoll centrifugation for sperm
      selection.
AB  - We compared the efficiency of different methodological variations of the
      centrifugation through discontinuous Percoll gradients (PC) to improve semen
      samples in the laboratory. Five different combinations of the number, volume and
      density of PC layers were assayed in 14 semen samples presenting various
      qualities. Each specimen was divided into five aliquots and processed
      simultaneously. The percentage of spermatozoa showing optimal movement (VAP > 30
      microns s-1 and STR > 80%) after PC selection when the number of gradients was
      reduced to three or two (PC-3: 43.3%, PC-2: 41.3%) and when the volume of layers
      was diminished to 0.5 ml (mPC-3: 44.2%, and mPC-2: 48.1%), was higher than in
      classical columns with four gradients of 1 ml (PC-4: 26.3%). The absolute
      recovery of optimal sperm was better with PC-2, mPC-2 and mPC-3. In samples
      showing low concentration or motility of spermatozoa, mPC-2 was the most
      effective technique. PC-2 and mPC-2 showed a tendency to eliminate more red blood
      cells contaminating the samples. Straight line velocity and straightness were
      similarly improved by all the methods. We conclude that the technique of PC
      centrifugation with only two gradients is simpler and more effective for sperm
      selection and in cases of poor samples can be used with low-volume layers.

PMID- 7639346
TI  - The influence of a mineral oil overlay on the zona pellucida binding potential of
      human spermatozoa.
AB  - The objective of the study was to evaluate the effect of mineral oil on zona
      pellucida binding potential of human spermatozoa. The study compared zona binding
      using micro volume droplets under mineral oil as apposed to micro droplets in
      cryopreservation straws. Spermatozoa from eight proven fertile sperm donors were
      used. One hundred and fifty five matched hemizonae in 50 microliters, 100
      microliters and 200 microliters insemination sperm droplets were co-incubated;
      (i) under mineral oil and (ii) 0.5 ml plastic cryopreservation straws. The
      results were analysed to determine the number of the zona bound spermatozoa
      during each experiment. Microvolumes with an oil overlay had a decrease in sperm
      bound per hemizona of 38% (mean +/- SD; 563 +/- 415 vs. 921 +/- 597), 51% (mean
      +/- SD; 392 +/- 359 vs. 800 +/- 566 sperm) and 18% (mean +/- SD; 502 +/- 369 vs.
      618 +/- 445) in 200 microliters, 100 microliters and 50 microliters respectively,
      compared to microvolumes in cryopreservation straws. It was concluded that
      mineral oil may have some detrimental factors which interfere with zona binding
      of spermatozoa.

PMID- 7639347
TI  - Metallothionein binding zinc inhibits nuclear chromatin decondensation of human
      spermatozoa.
AB  - Nuclear chromatin decondensation (NCD) of the human spermatozoa was induced by 1%
      sodium dodecyl sulphate (SDS). NCD of the spermatozoa induced in healthy and
      fertile men was significantly stronger and at higher rates than that in infertile
      men. In 1% SDS with 6 mM zinc chelating EDTA, metallothionein (MT) significantly
      enhanced NCD in a healthy man. In contrast MT alone significantly inhibited sperm
      NCD. Sperm NCD rate induced by 1% SDS in 10 infertile men was significantly
      inhibited by adding 75 or 750 micrograms ml-1 of MT. By adding 1.5 mM zinc, MT at
      concentrations of 0.75, 7.5, 75, or 750 micrograms ml-1, enhanced the inhibitory
      effect of 1.5 mM zinc. This suggested that thiols in the MT could, when liberated
      from zinc by zinc-chelating EDTA, induce sperm decondensation by cleaving
      stabilizing S-S bridges and that zinc bound to MT could exert a chromatin
      stabilizing effect mediated by the zinc dependent type of chromatin stability.
      The present study suggested that zinc bound to MT, which is secreted mainly from
      the prostate gland, is one factor that contributes to the chromatin stabilizing
      effect of human prostatic fluid.

PMID- 7639348
TI  - A case of decapitated spermatozoa in an infertile man.
AB  - A case of headless or decapitated spermatozoa of an infertile man is reported.
      The 33-year-old patient showed almost normal spermiogram except for a high
      percentage (more than 90%) of headless spermatozoa. Both hypoosmotic swelling and
      zona-free hamster egg tests showed that most headless spermatozoa appeared to be
      normal in their function as tails. The ultrastructure of the ejaculated
      spermatozoa was observed using a surface replica method and by conventional
      ultrathin sectioning. The headless spermatozoa were almost normal in structure
      except for the absence of the head. Tailless heads were rarely observed.
      Varieties of ultrastructural abnormalities were observed in spermatozoa heads.
      Among them, abnormalities in the nuclear membrane covering the posterior pole of
      the nucleus were prominent. The implantation fossa and the basal plate were not
      formed. Instead, the nuclear membrane with numerous nuclear pores was found in
      this region. The decapitation seemed to take place between the region of the
      basal plate and the proximal centriole.

PMID- 7639349
TI  - XY-quadrivalent association and sterility in a man carrier of a reciprocal
      autosomal translocation involving the whole arm of an acrocentric chromosome
      t(2;15)(q21.3;cen).
AB  - Meiotic and synaptonemal complex studies using electron microscopy were carried
      out on an infertile man with a 46,XY t(2q;15p). Synaptonemal complex analysis
      showed terminal asynapsis in the totality of quadrivalents and a high and
      significant frequency of association with the XY vesicle (80%), possibly related
      to the high amount of satellite DNA of the acrocentric chromosome 15. In this
      translocation carrier, the XY quadrivalent association at pachytene stage is
      positively correlated with the degree of spermatogenic breakdown after pachytene
      stage. Whether association with the non-paired segment represents the causative
      factor or only a secondary effect has still to be clarified.

PMID- 7639350
TI  - Embedding resin space, water contents and chromatin compaction in rabbit sperm
      nuclei: electron microscopic X-ray spectrophotometry of a brominated probe.
AB  - EPON labelled with bromide was used to embed ejaculated rabbit spermatozoa, with
      the hypothesis that it replaces cell water. X-Ray spectrophotometric
      microanalysis of sperm nuclei, of egg yolk (an internal standard containing
      roughly 50% water) and of surrounding embedding resin, revealed that a part of
      the bromide was bound to the biological components. These latter were saturated
      when bromide was added in higher concentrations, and the increase in measured
      bromide could be used to calculate absolute resin contents in sperm nuclei which
      gives a mean value of 22.62%. Most nuclei (60.80%) were well condensed and
      displayed a mean resin space close to 17% of the total nuclear volume. The less
      condensed nuclei had a mean resin space close to 28%. The use of an internal
      standard revealed that calculated values were underestimated by 4%.

PMID- 7639351
TI  - Histological and endocrinological investigations of cyclosporine effects on the
      rat testis.
AB  - To investigate the effects of cyclosporine on spermatogenesis and
      endocrinological function of the testis, cyclosporine was administered
      subcutaneously to mature male Sprague-Dawley rats. Four and 6 weeks after the
      termination of cyclosporine administration (40 or 60 mg kg-1), the diameter of
      seminiferous tubules was diminished. The percentage of tubules with spermatozoa
      was decreased 6 weeks after the termination of cyclosporine treatment (20-60 mg
      kg-1). However, tubular wall thickness did not change throughout the experiment.
      Serum follicular stimulating hormone level increased significantly immediately
      after termination of cyclosporine administration dose-dependently, while the
      serum levels' luteinizing hormone and testosterone did not alter throughout the
      experiment. It is strongly suggested that cyclosporine impairs spermatogenesis
      and Sertoli cell function, although Leydig cell function is not injured.

PMID- 7639352
TI  - Effects of the platelet-activating factor receptor antagonist BN 52021 on
      hematologic variables and blood loss during and after cardiopulmonary bypass.
AB  - Cardiopulmonary bypass (CPB)-induced thrombocytopenia and leukopenia is augmented
      after heparin reversal of protamine. Platelet-activating factor (PAF) might be
      implicated in these disorders. To evaluate the effects of PAF on the hematologic
      disorders and blood loss during and after CPB, patients were pretreated with BN
      52021, a PAF receptor antagonist, or a placebo. BN 52021 (120 mg) (n = 13) or
      placebo (n = 15) were infused intravenously before vascular cannulation and
      before cross-clamp release. Platelet and leukocyte counts were assessed in venous
      blood before and after the first dose of BN 52021 or placebo, 2 min after the
      beginning of CPB (at the entry of the oxygenator), at the end of CPB, 1, 15, and
      30 min after protamine infusion, and 6 and 24 h after CPB. The decrease in
      platelet and leukocyte counts were the same between groups during and after CPB
      and after protamine infusion. Bleeding times were not modified by the
      pretreatment of patients with BN 52021. During surgery, blood loss reached 1660
      +/- 297 mL in the BN 52021 group and 1599 +/- 283 mL in the placebo group (P >
      0.05). Forty-eight hours postoperatively, the chest tube outputs were not
      different between groups (1460 +/- 418 mL vs 1640 +/- 362 mL in the BN 52021 and
      placebo groups, respectively). This study shows that BN 52021 infusion did not
      change the hematologic variables studied. Moreover, a PAF antagonist pretreatment
      did not protect the patients against CPB- or protamine-induced hematologic
      changes.

PMID- 7639353
TI  - Experimental hypothermia: effects of core cooling and rewarming on hemodynamics,
      coronary blood flow, and myocardial metabolism in dogs.
AB  - Conflicting results have been reported as to the extent that cardiovascular
      function can be reestablished after rewarming from hypothermia. We measured
      hemodynamic function, myocardial metabolism and tissue water content in dogs core
      cooled to 25 degrees C and later rewarmed. At 25 degrees C left ventricular (LV)
      systolic pressure (LVSP) was 54% +/- 4%, maximum rate of LV pressure rise (LV
      dP/dtmax) 44% +/- 5%, aortic pressure (AOP) 50% +/- 6%, heart rate (HR) 40% +/-
      0%, cardiac output (CO) 37% +/- 5%, myocardial blood flow (MBF) 34% +/- 5%, and
      myocardial oxygen consumption (MVO2) 8% +/- 1%, compared to precooling. Stroke
      volume (SV) and LV end-diastolic pressure (LVEDP) were unchanged. As normothermia
      (37 degrees C) was reestablished, the depression of cardiac function and
      myocardial metabolism remained the same as that at 25 degrees C: LVSP 71% +/- 6%,
      LV dP/dtmax 73% +/- 7%, SV 60% +/- 9%, AOP 70% +/- 6%, CO 57% +/- 9%, MBF 53% +/-
      8%, and MVO2 44% +/- 8% HR, in contrast, recovered to precooling values. The
      arterial concentrations of glucose and free fatty acids (FFA) did not change
      significantly during the experimental period, whereas an increase in lactate of
      nonmyocardial origin appeared after rewarming. Increased myocardial contents of
      creatine phosphate and water were found during both hypothermia and rewarming.
      The present study demonstrates a persistent depression of cardiac function after
      hypothermia and rewarming in spite of adequate energy stores. Thus, a direct
      influence on myocardial contractile function by the cooling and rewarming process
      is suggested.

PMID- 7639354
TI  - Midazolam pharmacokinetics in patients undergoing abdominal aortic surgery.
AB  - Fentanyl and its analogs are eliminated slowly by patients having abdominal
      aortic surgery. This is principally due to larger volumes of distribution,
      compared to the pharmacokinetics determined in other surgical patients.
      Midazolam, like these opioids, is a lipophilic organic base, suggesting that it
      may also have a larger volume of distribution in patients undergoing abdominal
      aortic reconstruction. The pharmacokinetics of intravenous midazolam, 0.25 mg/kg,
      were determined in patients undergoing elective infrarenal abdominal aortic
      surgery. The mean (+/- SD) age of the patients was 66.7 +/- 9.2 yr, and their
      mean weight was 74.3 +/- 12.7 kg. Blood samples were drawn at increasing
      intervals for 24 h after administration of midazolam, and serum midazolam
      concentrations were measured by gas-liquid chromatography. A 3 compartment model
      best described the concentration versus time data. Simulations of the times
      required for 20%, 50%, and 80% decreases in midazolam concentrations after
      stopping an infusion that maintains a constant plasma midazolam concentration
      were performed, comparing pharmacokinetic variables from this study with
      previously published values. Metabolic clearance was 361 +/- 97 mL/min. Rapid
      intercompartmental clearance was 2197 +/- 997 mL/min and slow intercompartmental
      clearance, 481 +/- 225 mL/min. The volume of the central compartment (Vc) and the
      volume of distribution at steady state (Vdss) were 5.8 +/- 5.3 L and 118.2 +/-
      70.4 L, respectively. The elimination half-life was 6.3 +/- 3.6 h, 1.5- to 3-fold
      longer than has been previously reported in patients undergoing surgery. Compared
      to previously published studies of other groups of patients, metabolic clearance
      of midazolam was slower in patients undergoing abdominal aortic surgery.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7639355
TI  - Halothane protects the isolated rat myocardium against excessive total
      intracellular calcium and structural damage during ischemia and reperfusion.
AB  - A recent study from our laboratory demonstrated halothane to be a powerful
      protectant of the isolated rat heart during reperfusion after normothermic
      cardioplegic arrest. It was speculated that this protective effect might be due
      to prevention of excessive intracellular calcium. The aim of the present study
      was to evaluate the effect of halothane on the total intracellular calcium (Ca2+)
      content and on myocardial structure both at the end of normothermic cardioplegic
      arrest and at the end of reperfusion. Isolated perfused rat hearts were perfused
      for a control period of 30 min, followed by 40 min of normothermic cardioplegic
      arrest with or without reperfusion for 30 min. Halothane (1.5%) was administered
      continuously before and after arrest. Halothane caused a significant decrease of
      intracellular Ca2+ at the end of normothermic cardioplegic arrest and after
      reperfusion. Myocardial morphology was assessed by extensive light microscopy and
      ultrastructure was evaluated by electron microscopy. Grading of ischemic damage
      showed that exposure to normothermic cardioplegia resulted in marked ischemic
      injury, regardless of whether the hearts were treated with halothane. Reperfusion
      in the presence of halothane caused a significant reversal of ischemic damage and
      almost complete ultrastructural repair, whereas untreated hearts still exhibited
      severe edema, contracture, and contracture bands. Our results indicate that the
      beneficial effects of halothane on myocardial structural recovery during
      reperfusion is associated with a reduction in excessive intracellular Ca2+. The
      exact mechanism of this protective action is under investigation.

PMID- 7639356
TI  - Pharmacokinetics do not explain the absence of an anesthetic effect of
      perfluoropropane or perfluoropentane.
AB  - In conflict with the prediction of the Meyer-Overton hypothesis, perfluoropropane
      (C3F8) and perfluoropentane (C5F12) have no anesthetic effect in rats. To test
      whether this resulted from a failure of the inspired drugs to reach the brain, we
      determined the increase in partial pressures of C3F8 and C5F12 in the blood and
      brains of rats exposed to 0.65 ata of each drug. C3F8 and C5F12 blood/gas
      partition coefficients equaled 0.00125 +/- 0.00037 (mean +/- SD, n = 9) and
      0.00277 +/- 0.00082 (n = 4), and brain/gas partition coefficients equaled 0.0119
      +/- 0.0002 (n = 4) and 0.0229 +/- 0.0055 (n = 7), respectively. As a fraction of
      the inspired value (Pa/PI), the partial pressures of C3F8 and C5F12 in blood (Pa)
      were 0.99 +/- 0.12 and 0.69 +/- 0.19, respectively, 30 min after administration.
      The increases in cerebral (Pb) partial pressures of both drugs paralleled the
      arterial increases (Pb/PI = 0.85 +/- 0.02, and 1.05 +/- 0.03, respectively at 30
      min), with C3F8 reaching a plateau at 2 h of 96% +/- 4% of the partial pressure
      of inspired gas. We conclude that failure of C3F8 and C5F12 to reach the brain
      does not account for the absence of an anesthetic effect of these compounds.

PMID- 7639357
TI  - A cutoff in potency exists in the perfluoroalkanes.
AB  - Anesthetic potencies (minimum alveolar anesthetic concentration [MAC]) of
      perfluoroalkanes from perfluoromethane to perfluorooctane were assessed in male
      rats to determine whether a cutoff in anesthetic effect (i.e., an absence of any
      anesthetic effect) exists for the larger compounds in this series. Although
      hyperbaric measurements suggested a MAC of 38.9 +/- 6 atm (mean +/- SD) for CF4,
      this pressure was nearly identical to the lethal pressure of 41.1 +/- 5.8 atm.
      Hyperbaric studies of C2F6 caused death without causing anesthesia, the lethal
      pressure being 23.8 +/- 2.6 atm. Results from studies of additivity with
      desflurane suggested that the MAC of CF4 was 66.5 +/- 13.4 atm at an average CF4
      test partial pressure of 17.7 +/- 4.0 atm (i.e., 17.7 atm of CF4 decreased the
      MAC of desflurane by 26.6%). Studies of additivity with desflurane, isoflurane,
      or halothane did not reveal an anesthetic effect of C2F6 at a pressure of 7.2 +/-
      0.4 atm, or of larger perfluoroalkanes near to or at their saturated vapor
      pressures. We conclude that a cutoff in anesthetic potency for perfluoroalkanes
      exists between perfluoromethane and perfluoroethane.

PMID- 7639358
TI  - Molecular properties of the "ideal" inhaled anesthetic: studies of fluorinated
      methanes, ethanes, propanes, and butanes.
AB  - We examined 35 unfluorinated, partially fluorinated, and perfluorinated methanes,
      ethanes, propanes, and butanes to define those molecular properties that best
      correlated with optimum solubility (low) and potency (high). Limited additional
      data were obtained on longer-chained alkanes. Using standard techniques, we
      assessed anesthetic potency (minimum alveolar anesthetic concentration [MAC] in
      rats); vapor pressure; stability in soda lime; and solubility in saline, human
      blood, and oil. If nonflammability, stability, low solubility in blood,
      clinically useful vapor pressures, and potency permitting delivery of high
      concentrations of oxygen are essential components of an anesthetic that might
      supplant those presently available, our data indicate that such a drug would have
      three or four carbon atoms with single or dual hydrogenation of two carbons,
      especially terminal carbons. We conclude that: 1) smaller and larger molecules
      and lesser hydrogenation provide insufficient potency; 2) high vapor pressures of
      smaller molecules do not permit the use of variable bypass vaporizers; 3) greater
      hydrogenation enhances flammability, and complete hydrogenation decreases
      potency; 4) internal hydrogenation decreases stability; and 5) greater
      hydrogenation increases blood solubility.

PMID- 7639359
TI  - Effects of intravenous anesthetics on phosphatidylinositol turnover in rat
      cerebral cortical prisms.
AB  - Noradrenergic pathways in the brain have been thought to be related to the site
      of anesthetic action. Norepinephrine (NE) in the central nervous system
      stimulates phosphatidylinositol (PI) turnover through alpha 1-adrenergic
      receptors. The present study was designed to examine the effects of intravenous
      anesthetics on NE-induced PI turnover in rat cerebral cortical prisms. NE-induced
      inositol monophosphate (IP1) formation was inhibited by droperidol (dose for 50%
      inhibition [ID50], 0.0258 +/- 0.00023 microM [mean +/- SE]), fentanyl (2.36 +/-
      0.0017), diazepam (201 +/- 2.12), and thiamylal (231 +/- 1.94) in a dose
      dependent manner, but was not affected by ketamine. Naloxone or flumazenil did
      not attenuate the inhibitory effect of fentanyl or diazepam on NE-induced IP1
      formation. The results suggest that these effects on the PI turnover in the
      cortex may be related to their pharmacologic properties including the anesthetic
      action.

PMID- 7639360
TI  - The effect of clonidine on the activity of neurons in the rat dorsal raphe
      nucleus in vitro.
AB  - The dorsal raphe (DR) nucleus is a system of nuclei in the midline of the lower
      brainstem, which is considered one of the most important nuclei in the modulation
      of pain in the central nervous system. Central noradrenergic systems play an
      important role in the control of cardiovascular regulation and pain transmission.
      Clonidine, an alpha 2-adrenergic agonist is used extensively in anesthesia
      research. In this study, we evaluated the involvement of clonidine in the
      activity of DR nucleus and its possible role in pain modulation. Seventy-four
      neurons within the DR nucleus in the rat brainstem slice preparation were tested
      using extracellular recording techniques. Application of noradrenaline (NA), 50
      mumol/L, induced firing activity in 68 neurons tested (92%). NA produced a
      regular long-lasting firing activity on the DR neurons. Fifty-six neurons (88%)
      previously excited by NA were inhibited by clonidine, 20 mumol/L. Clonidine
      suppressed the firing activity of neurons. The results indicate that the firing
      of DR neurons was under noradrenergic influence and was inhibited by clonidine,
      which in turn alters nociception by modifying the central serotonergic system.

PMID- 7639361
TI  - Spinal potentiation and supraspinal additivity in the antinociceptive interaction
      between systemically administered alpha 2-adrenoceptor agonist and cocaine in the
      rat.
AB  - We studied the antinociceptive interaction of systemically administered
      medetomidine, a selective alpha 2-adrenoceptor agonist, with cocaine in the
      tailflick and hotplate tests in rats. In intact rats, both medetomidine alone (25
      300 micrograms/kg subcutaneously [SC]) and cocaine alone (10-30 mg/kg
      intraperitoneally [IP]) produced a dose-dependent antinociception in the
      supraspinally mediated hotplate test, and their combination (medetomidine 25
      micrograms/kg+cocaine 10-20 mg/kg) produced an additive antinociceptive effect.
      In the spinally mediated tailflick test, only medetomidine alone produced a
      significant antinociceptive effect both in intact and spinal rats, whereas
      cocaine alone produced a marginally significant antinociceptive effect in the
      tailflick test only at the highest dose used (30 mg/kg) and only in intact rats.
      The combination of medetomidine (25 micrograms/kg SC) with cocaine (10-20 mg/kg
      IP) produced potentiation of antinociception in the tailflick test both in intact
      and spinal rats. The results indicate that at the supraspinal level there is an
      additive antinociceptive interaction between cocaine and medetomidine, whereas at
      the spinal level cocaine potentiates the medetomidine-induced antinociception
      independent of supraspinal mechanisms. The results further support previous
      evidence indicating that antinociception produced by a systemically administered
      alpha 2-adrenergic drug alone is mainly due to spinal mechanisms, whereas that by
      systemically administered cocaine alone is mainly due to supraspinal mechanisms.

PMID- 7639362
TI  - Isoflurane modulates phorbol myristate acetate-, prostaglandin D2-, and
      prostaglandin E2-induced alterations in hepatic flow and metabolism in the
      perfused liver in fasted rats.
AB  - Protein kinase C (PKC) is thought to play an important role in the regulation of
      hepatic flow and metabolism in the liver. The activation of PKC has been
      implicated in pathologic responses of the organisms to immunologically active
      substances including endotoxin. The effects of volatile anesthetics on the
      hemodynamic and metabolic alterations associated with PKC activation were studied
      using isolated liver perfusion. The liver was isolated from overnight-fasted,
      male Sprague-Dawley rats, and placed in a recirculating perfusion-aeration
      system. The liver was perfused through the portal vein at a constant pressure of
      12 cm H2O. Isoflurane at a concentration of 3% maintained hepatic flow, reduced
      oxygen consumption, and transiently enhanced lactate production. Phorbol 12
      myristate 13-acetate (PMA), a potent activator of PKC, at an initial
      concentration of 80 nM decreased hepatic flow and oxygen consumption, and
      enhanced lactate production. Isoflurane significantly attenuated the PMA-induced
      alterations in hepatic flow, oxygen consumption, and lactate production. A
      similar inhibition of the PMA-induced alterations was observed in the liver
      treated with halothane at 2%. Isoflurane attenuated the flow reduction and
      stabilized the oxygen consumption after the administration of prostaglandin D2
      (PGD2) and E2 (PGE2), possible mediators of PMA. Isoflurane, and presumably other
      volatile anesthetics, may elicit beneficial effects on the liver by attenuating
      the PKC-mediated alterations in hepatic hemodynamics and metabolism when PKC in
      the liver is activated through pathologic mechanisms.

PMID- 7639363
TI  - Recovery from outpatient laparoscopic tubal ligation is not improved by
      preoperative administration of ketorolac or ibuprofen.
AB  - The analgesic efficacy of a single dose of ketorolac or ibuprofen given
      preoperatively was assessed in healthy outpatients undergoing general anesthesia
      for laparoscopic tubal ligation. Fifty patients were randomized to receive either
      ketorolac 60 mg intravenously (i.v.), ibuprofen 800 mg orally, or placebo in a
      double-blind manner. Anesthesia was induced with fentanyl 2 micrograms/kg,
      thiopental 5 mg/kg, and either vecuronium 0.1 mg/kg or succinylcholine 1.5 mg/kg
      i.v. and was maintained with nitrous oxide 67% in oxygen and isoflurane. Patients
      were assessed at 15-min intervals in the postanesthesia care unit (PACU) and
      treated for pain with i.v. morphine by protocol. Patients were evaluated for
      pain, analgesic requirements, side effects, and recovery times. After discharge,
      patients completed questionnaires to assess pain, analgesic use, and side effects
      6 and 24 h postoperatively. Parenteral morphine was required in 80% of patients
      in the control group, and 73% of patients in both treatment groups, and the
      difference was not statistically significant. The dose of parenteral morphine
      required in the PACU was not different between the control (7 +/- 1.2 mg),
      ibuprofen (5.7 +/- 1.4 mg), and ketorolac (6.1 +/- 1.4 mg) groups. There was no
      difference between groups in terms of pain visual analog scale (VAS) scores,
      fatigue VAS scores, recovery times, or the incidence of postoperative nausea and
      vomiting. The preoperative administration of either parenteral ketorolac or oral
      ibuprofen did not decrease postoperative pain or side effects when compared to
      placebo in this outpatient population.

PMID- 7639364
TI  - Transdermal scopolamine for the reduction of postoperative nausea in outpatient
      ear surgery: a double-blind, randomized study.
AB  - We evaluated the effect of transdermal scopolamine on the incidence of
      postoperative nausea and vertigo after outpatient ear surgery (exploratory
      tympanotomy, mastoidectomy, or endolymphatic sac and oval and round window
      surgery) in a double-blind, placebo-controlled study. A transdermal patch
      containing either scopolamine (n = 19) or placebo (n = 20) was placed behind the
      nonsurgical ear 2 h before surgery. Anesthesia was induced with thiopental (4-6
      mg/kg intravenously [i.v.]), sufentanil (0.5 microgram/kg i.v.), and vecuronium
      (0.1 mg/kg i.v.) and maintained with isoflurane (0.2%-2%) and nitrous oxide (70%)
      in oxygen. Patients were observed postoperatively in the recovery room and after
      discharge for 72 h. There was no significant difference between groups with
      respect to time in recovery room, time to discharge, incidence of in-house
      nausea, vomiting, amount of antiemetics required, or postoperative visual analog
      scale (VAS) scores while in the hospital. After discharge, there were lower VAS
      nausea scores (by repeat measures analysis, P < 0.05) and a lower reported
      incidence of nausea (31% vs 62%; P < 0.05) and vertigo (6.2% vs 25%; P < 0.05) in
      the active patch group versus the placebo group. There was a higher incidence of
      dry mouth in the active patch group (44% vs 25%). Seven patients did not complete
      the study due to failure to keep the patch in place or failure to return the
      diary from home; and one patient from the placebo patch group was admitted for
      uncontrolled nausea and vomiting. The authors concluded that transdermal
      scopolamine is effective in reducing, but not eliminating, postoperative nausea
      and vertigo after discharge in outpatient ear surgery.

PMID- 7639365
TI  - An isobolographic study of epidural clonidine and fentanyl after cesarean
      section.
AB  - Although the epidural administration of clonidine and fentanyl provides pain
      relief after surgery, the interaction between the two drugs has not been examined
      formally. This study used an isobolographic method to determine whether
      epidurally administered fentanyl and clonidine interact in an additive or
      synergistic manner. Ninety women with moderate to severe pain after elective
      cesarean section under epidural anesthesia were studied. Using a randomized,
      double-blind protocol, we assigned each patient to receive a single epidural
      injection of one of three doses of fentanyl, clonidine, or a fixed ratio
      combination. Pain relief, blood pressure (BP), heart rate (HR), and sedation were
      measured 15 min after injection. Each drug alone and in combination produced
      analgesia, as measured by pain relief scores, and reduced need for intravenous
      morphine. Although the effective dose producing analgesia in 50% of patients
      (ED50) for the mixture was only 52% of that predicted by an additive interaction,
      this did not differ significantly from additivity, likely due to large
      variability. Clonidine, alone or in combination with fentanyl, produced a minor
      reduction in BP, but did not affect HR or cause more sedation than fentanyl.
      Unlike studies in rodents, this clinical study did not demonstrate synergy
      between fentanyl and clonidine. This could reflect a true species difference or
      differences in methodologies used. Nonetheless, a reduced dose of fentanyl and
      clonidine can be combined for excellent analgesia.

PMID- 7639366
TI  - Previous wet tap does not reduce success rate of labor epidural analgesia.
AB  - Whether unintentional dural puncture (wet tap) during a previous labor epidural
      increases the failure rate of epidural analgesia for later deliveries is
      controversial. In this study, charts of 47 women with a previous wet tap who
      received epidural analgesia for labor were compared to those of 500 consecutive
      women receiving epidural analgesia in 1991 and, separately, to 44 women matched
      for month of delivery, previous epidural without a wet tap, and the same
      anesthesiologist. In comparison to the 500 consecutive control patients, women
      with a previous wet tap had a lower incidence of epidural catheter manipulation
      for inadequate block (9% vs 20%), but a similar incidence of catheter removal for
      failed block (4% vs 6.7%). In comparison to matched control patients, women with
      a previous wet tap had a similar incidence of epidural catheter manipulation and
      removal for inadequate or failed blocks. Epidural analgesia was considered
      successful in 93% of cases and 89% of matched control subjects by chart review.
      Two women (4%) with previous wet tap experienced a second wet tap during
      attempted epidural catheterization, compared to 0% in 500 consecutive patients (P
      < 0.001). These data suggest that there is no decrease in the success rate of
      epidural analgesia in women with a previous wet tap, although the chance for a
      repeated wet tap may be increased.

PMID- 7639367
TI  - Measurements of protein binding of lidocaine throughout pregnancy.
AB  - Pregnancy-related anatomic and physiologic changes result in altered
      pharmacologic and toxicologic responses to local anesthetics. Reductions in serum
      protein binding have been implicated in enhanced toxic effects. Previous studies
      have demonstrated these reductions in protein binding only in the term
      parturient. The present study defines the pattern of protein binding changes of
      lidocaine throughout gestation. Venous samples were obtained from pregnant
      patients of varying gestational age, as well as from nonpregnant control
      patients. The percent free drug at a fixed concentration (2 micrograms/mL) was
      determined for each sample using an ultrafiltration technique. The free
      concentration of lidocaine increased significantly throughout gestation,
      reflecting a corresponding decrease in protein binding. However, these changes
      were small compared to those in the nonparturient, which suggests that toxicity
      to lidocaine should not vary during pregnancy.

PMID- 7639368
TI  - Preoperative analgesia with epidural morphine.
AB  - In a prospective double-blind study, we examined the effects of preoperative
      epidural morphine associated with general anesthesia (GA) on intra- and
      postoperative analgesic requirements over a 3-day postoperative period. Twenty
      patients scheduled for major intraabdominal surgery were randomly assigned to two
      groups: a control group (n = 10) and an epidural group (n = 10) which received an
      epidural injection of 5 mg of preservative-free morphine in 10 mL of 0.9% saline.
      Afterward, both groups received the same GA. Postoperative pain relief was
      achieved with intravenous (IV) boluses of morphine using a patient-controlled
      analgesia device. We found smaller opioid requirements in the epidural group than
      in the control group for intraoperative fentanyl (465 +/- 179 micrograms vs 983
      +/- 682 micrograms), for postoperative morphine at 12 h (3.1 +/- 3 mg vs 21.4 +/-
      13.8 mg) and 24 h (9.1 +/- 6.4 mg vs 20.6 +/- 9.8 mg), and for the cumulated
      needs over the 3-day postoperative period (37 +/- 24 mg vs 86 +/- 42 mg). The
      consumption of IV morphine by the control group decreased over time (P < 0.001, r
      = 0.44), whereas, in the epidural group, consumption remained constant and small
      during the 3 days. The maximum pain score was significantly lower in the epidural
      group than in the control group at 24 h (0.65 +/- 2.4 vs 3 +/- 2), at 36 h (0.3
      +/- 0.6 vs 3 +/- 2.7), and at 60 h (0.1 +/- 0.3 vs 1.8 +/- 1.2) after surgery.
      These results suggest that a single epidural injection of 5 mg of morphine before
      major surgery produces intra- and postoperative pain relief for at least 3 days.

PMID- 7639369
TI  - Nifedipine-induced analgesia after epidural injection in rats.
AB  - We explored the analgesic effect of epidural nifedipine in male Sprague-Dawley
      rats. By using an implanted epidural catheter, the rats were given 35 microL of
      dimethylsulfoxide (DMSO) alone or DMSO containing 2.5, 5, 10, or 20 microM of
      nifedipine. Analgesia was measured by tailflick (TF) involving spinal reflexes,
      and by hotplate (HP) requiring an intact central nervous system. The latencies
      were recorded up to 120 min after the injection. The cutoff time of the noxious
      stimuli was 20 s in the TF and 60 s in the HP to prevent tissue damage. The TF
      technique revealed a significant difference from the control at doses of 5, 10,
      and 20 microM with no difference among the groups. Maximum latencies (cutoff
      time) lasted for 15, 30, and 40 min at doses of 5, 10, and 20 microM,
      respectively. The HP technique disclosed a dual effect: a significant decrease at
      the dose of 2.5 microM, no effect at 5 microM, and an increase at 10 and 20
      microM. However, the median latency did not reach the cutoff time. We conclude
      that nifedipine, given epidurally, possesses antinociceptive properties at the
      dose of 5 microM and higher, detected better by the TF than HP. Our data suggest
      that the antinociceptive effect of nifedipine, at the studied doses, is more
      prominent at the spinal than the supraspinal level.

PMID- 7639370
TI  - Single versus staged epidural injections of 0.75% bupivacaine: pharmacokinetic
      and pharmacodynamic effects.
AB  - Epidural anesthesia may be performed as a single injection or by staged doses.
      Thirty patients undergoing primary total hip replacement were randomly assigned
      to have epidural anesthesia using a single injection or a staged technique with
      25 mL of 0.75% bupivacaine. Arterial plasma bupivacaine concentrations were
      significantly higher in the single injection group for the first 15 min but were
      not significantly different thereafter. Peak bupivacaine concentrations did not
      differ significantly between groups, but the time to achieve the peak
      concentration was delayed by staging injections (P = 0.001). Hemodynamic effects
      were similar between groups. Resolution of thoracic sensory block through T12 and
      duration of motor block measured by Bromage scale were both significantly longer
      in the staged injection group (P < 0.01). The method of epidural injection may
      affect resolution of neural block and the time to reach peak arterial plasma
      concentration of local anesthetic.

PMID- 7639371
TI  - Propofol infusion during regional anesthesia: sedative, amnestic, and anxiolytic
      properties.
AB  - We examined the plasma concentrations and resultant clinical effects produced by
      four different propofol bolus infusion regimens in 98 healthy males undergoing
      elective urologic procedures under regional anesthesia. Patients were randomly
      assigned to one of four propofol dosage groups. In Groups 1-4, loading doses of
      propofol equal to 0.2, 0.4, 0.5, or 0.7 mg/kg intravenously, respectively, were
      followed by fixed-rate propofol infusions of 0.5, 1, 2, or 4 mg.kg-1.h-1,
      respectively, during the regional block procedure. Sedation (sleepiness) was
      assessed independently by the patient and a blinded observer using 100-mm visual
      analog scales. Intraoperative amnesia was assessed using picture recall. Sedation
      scores increased in a dose-dependent fashion (13 +/- 19, 21 +/- 19, 45 +/- 28,
      and 73 +/- 26 mm at 30 min in Groups 1-4, respectively). Within a given dosage
      group, sedation scores were stable during the maintenance infusion period. Mean
      plasma propofol concentrations increased with higher propofol infusion rates
      (0.16 +/- 0.3, 0.18 +/- 0.1, 0.47 +/- 0.2, and 1.1 +/- 0.8 microgram/mL at 30 min
      in Groups 1-4, respectively). However, significant variability was observed among
      individual patient sedation scores and plasma propofol concentrations. Anxiety
      scores decreased in all four propofol infusion groups during the maintenance
      period. Hemodynamic variables and hemoglobin oxygen saturation values were
      similar in all four treatment groups. Recovery from propofol's central effects
      was rapid after discontinuation of the propofol infusion, and the incidence of
      side effects was low. Recall of intraoperative events was more commonly observed
      in the lower-dosage groups (86%, 96%, 58%, and 13% of patients in Groups 1-4,
      respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7639372
TI  - Comparison of methohexital and alfentanil on movement during placement of
      retrobulbar nerve block.
AB  - We compared the use of methohexital (0.5 mg/kg) with alfentanil (20
      micrograms/kg) as a drug for limiting movement and pain during the placement of a
      retrobulbar block (RBB). Thirty patients (ASA class I-III) were randomly assigned
      to receive either methohexital or alfentanil (15 patients in each group). All but
      two patients (87%) treated with alfentanil were awake and responsive to command.
      All of the patients given methohexital were unresponsive at the time of block
      placement. However, less movement was observed when patients were treated with
      alfentanil compared to methohexital (P < 0.0002). None of the patients treated
      with alfentanil complained of pain during placement of the RBB. No difference was
      detected in the incidence of respiratory depression. However, one patient who
      received alfentanil had a prolonged period of apnea (approximately 30 s) with a
      significant decrease in oxygen saturation. The incidence of nausea and vomiting
      and the time to discharge from the outpatient department were similar in the two
      groups. The results of this study suggest that alfentanil may be used as a single
      drug to limit movement during placement of retrobulbar block for ophthalmic
      surgery.

PMID- 7639373
TI  - Subcutaneously versus subfascially administered lidocaine in pain treatment after
      inguinal herniotomy.
AB  - We conducted a randomized, prospective, double-blind trial to compare the
      efficacy of subfascial (SF) versus subcutaneous (SC) lidocaine (10 mL 1%) given
      in the wound postoperatively through a catheter placed in the respective layer
      intraoperatively. The initial pain scores were similar in the two groups before
      injection of lidocaine. In the SC group, there was a reduction in pain scores
      during rest from 4 to 3 (P > 0.05), during cough from 6 to 5 (P > 0.05), and
      during mobilization from 7 to 5.5 (P > 0.05) at 15 min. In the SF group, the
      reductions in pain scores were from 4 to 2 (P < 0.05), from 6 to 3 (P < 0.05),
      and from 7 to 3 (P < 0.05), respectively. Supplemental analgesics after the
      lidocaine administration were needed earlier in the SC group than in the SF group
      (P < 0.01). We conclude that postoperative pain treatment with local lidocaine
      application after herniotomy has a better effect when applied in the SF, rather
      than the SC, layer.

PMID- 7639374
TI  - Interpleural infusion of 2% lidocaine with 1:200,000 epinephrine for
      postthoracotomy analgesia.
AB  - The value of intrapleural analgesia after thoracotomy is still controversial. We
      investigated the pharmacokinetics of interpleural analgesia in 14 patients with
      and without thoracic drainage (Groups TD+ and TD-, respectively) to determine the
      safety of the technique. The infusion led to a high steady-state concentration
      (Css) of 5.91 +/- 2.46 mg/mL in Group TD-. We then performed a placebo-controlled
      double-blind study on 16 patients to evaluate the analgesic effects of an
      interpleural infusion of 2% lidocaine using intravenous patient-controlled
      analgesia (PCA) with morphine and a visual analog scale score (VAS). In both
      studies an initial bolus of 3 mg/kg of 2% lidocaine was followed by an infusion
      of 1 mg.kg-1.h-1 for 48 h. The VAS score was slightly reduced after the bolus
      (6.6 +/- 1.0 vs 8.7 +/- 0.3; P < 0.05 vs the placebo group) but the cumulative
      doses of morphine were similar in both groups. There was a slight, but not
      sustained, improvement in pulmonary function test. In conclusion, interpleural
      analgesia by continuous infusion of lidocaine is poor after thoracotomy and may
      lead to blood levels in the toxic range.

PMID- 7639375
TI  - Echocardiographic evaluation of bupivacaine cardiotoxicity.
AB  - In nine pentobarbital anesthetized dogs, the global effects of bupivacaine on the
      heart were examined during and after the onset of bupivacaine cardiotoxicity. The
      onset of bupivacaine cardiotoxicity was followed by the use of echocardiography
      to determine the sequence of events. The overall sequence of changes in the
      heart, demonstrated by the echocardiographic images, was markedly impaired
      systolic function and right ventricular dilation. The right ventricular dilation
      was so profound that it was associated with a septal shift into the left
      ventricle. Right ventricular dilation was so profound that the ability to
      maintain the whole ventricle within the echocardiographic image was lost. Areas
      obtained from the left ventricle at the two time points studied (the half-time
      from the beginning of injection to the occurrence of asystole referred to as
      midway through the toxic episode and at asystole) exhibited a significant
      systolic dilation only midway through the toxic episode. The mean total dose of
      bupivacaine resulting in the dilation of the ventricles was 14.0 +/- 3.3 mg/kg.
      The mean arterial pressure was reduced from control by 46.9% +/- 8.8% midway
      through the toxic episode. The mean pulmonary arterial pressure exhibited no
      significant change from before the bupivacaine injection sequence. A variety of
      conduction changes seen midway through the toxic episode were widening of the QRS
      complex, inversion, bradycardia, premature ventricular contractions (PVCs), or a
      combination of these. PVCs, if seen at all, were only beginning to develop and no
      heart block was seen in any dog midway through the toxic episode.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7639376
TI  - Epidural morphine combined with epidural or intravenous butorphanol for
      postoperative analgesia in pediatric patients.
AB  - We performed a prospective, randomized, double-blinded study in 60 postoperative
      pediatric patients aged 6 wk to 7 yr to compare the efficacy of butorphanol given
      epidurally or intravenously in preventing the side effects of epidural morphine.
      Three groups of patients received 60 micrograms/kg epidural morphine; 20 patients
      also received epidural butorphanol 30 micrograms/kg, and 20 patients also
      received 30 micrograms/kg intravenous butorphanol. All patients were evaluated
      for analgesia, sedation, vomiting, urinary retention, pruritus, and respiratory
      depression for 24 h postoperatively. Although the overall incidence of side
      effects was not different in the three groups, the epidural butorphanol group had
      a significant decrease in severity of pruritus. Sedation was seen more frequently
      in the groups receiving butorphanol, but was most pronounced in the epidural
      butorphanol group. We conclude that butorphanol has little or no effect on the
      side effects of epidural morphine.

PMID- 7639378
TI  - Relative sodium current block by bupivacaine and lidocaine in neonatal rat
      myocytes.
AB  - Bupivacaine is more cardiotoxic than lidocaine and can produce fatal arrhythmias
      during accidental overdose or intravascular injection. Studies using Vmax in
      adult guinea pig myocytes suggest that this toxicity is due to the greater
      inhibition of sodium current by bupivacaine. Human neonates and cardiac tissue
      from neonatal animals show resistance to the cardiac effects of many local
      anesthetic and antiarrhythmic drugs, and a slower onset of use-dependent block.
      We used whole-cell patch clamp (20 degrees C, [Na]o = 50 mmol/L) to examine
      directly the kinetics of sodium current block by bupivacaine and lidocaine in
      ventricular myocytes from 1- to 2-day-old rats. We found that 1 microgram/mL
      bupivacaine and 5 micrograms/mL lidocaine produced equivalent amounts of use
      dependent block for protocols corresponding to 30-200 depolarizations per minute
      (cell resting potential of -85 mV). Block due to bupivacaine surpassed that from
      lidocaine (37.6% +/- 3.4% vs 26.4% +/- 2.7%) (P < 0.01) only after the resting
      membrane potential was hyperpolarized to -110 mV and the length of depolarization
      and repolarization were increased to nonphysiologic durations (1 s and 0.5 s,
      respectively). Double-pulse protocols were used to measure the underlying rate of
      onset and recovery from block. At these concentrations, blockade development was
      more than seven times slower for bupivacaine (4.11 +/- 0.32 s vs 0.57 +/- 0.06 s)
      (P < 0.01, and recovery from block was five times slower (10.81 +/- 0.54 s vs
      2.14 +/- 0.50 s) (P < 0.01). In these neonatal myocytes, bupivacaine does not
      produce more use-dependent block than lidocaine, and the effect of bupivacaine is
      limited by its slow binding to the sodium channel.

PMID- 7639377
TI  - Mivacurium after atracurium in children.
AB  - The effect of mivacurium after atracurium was evaluated in 36 children
      anesthetized with halothane-nitrous oxide-oxygen by measuring the force of
      contraction of the adductor pollicis during train-of-four stimulation at 0.1 Hz.
      The children were evaluated in two main groups. In Group 1 the effect of bolus
      doses of mivacurium after equipotent repeat doses of atracurium were evaluated.
      When the first twitch of the train-of-four response (T1) had recovered to 25% of
      control after a tracheally intubating dose of atracurium, a repeat dose of
      atracurium was given, on subsequent recovery to 25%, an equipotent dose of
      mivacurium was administered. In Group 2 when T1 had recovered to > 10% from 0.5
      mg/kg atracurium, a mivacurium infusion was started; the initial infusion rate
      was 4 micrograms.kg-1.min-1 with adjustments made to maintain 90%-99% depression
      of T1. Patients were allowed to recover spontaneously from the effect of the
      relaxants. In Group 1 prolongation of the effect of mivacurium was noted after
      atracurium; the recovery indices (25%-75% and 5%-95%) of mivacurium were longer
      than those seen when mivacurium is the sole relaxant but shorter than atracurium.
      In Group 2, 15 min after the start of the mivacurium infusion, the dose
      requirement was 3.7 +/- 0.3 micrograms.kg-1.min-1 (approximately about one-third
      that required after a tracheally intubating dose of mivacurium). The infusion
      requirement increased gradually (P < 0.0001) until, at 90 min of infusion, it was
      7.4 +/- 0.8 micrograms.kg-1.min-1. In Group 2 the recovery indices were similar
      to those seen when mivacurium is the sole relaxant given. When mivacurium is
      given after atracurium, evidence of the residual neuromuscular effects of the
      atracurium are detected beyond the usual recovery range.

PMID- 7639379
TI  - Quality of washed salvaged red blood cells during total hip replacement: a
      comparison between the use of heparin and citrate as anticoagulants.
AB  - A randomized, prospective study comparing heparin with citrate (ACD) as
      anticoagulant during red blood cell saving was performed in 10 ASA grade I-II
      patients undergoing primary total hip replacement. Blood samples were taken
      before and after surgery and at several steps during cell saving. In the heparin
      group, salvaged red cells showed normal values, with the exception of decreased
      filtrability and moderate hemolysis. More differences in red cell quality were
      found in the ACD group. Mean corpuscular volume was higher (110 vs 95 x 10(-12)
      mL), red cell distribution was increased (17% vs 13%), osmotic resistance was
      lower (0.54 vs 0.43 g NaCl/L at 50% hemolysis), antioxidative reserve capacity
      was lower (1.9 vs 4.6 U glutathione reductase per gram of hemoglobin) and there
      was more hemolysis (15% vs 11%). Despite the small volume of autologous blood
      retransfused (388 +/- 92 mL), the differences in vitro produced significantly
      higher free hemoglobin levels in the patients' plasma at the end of the operation
      (58 vs 23 mg/dL). We conclude that heparin is preferable to citrate as an
      anticoagulant during autotransfusion with cell washing and immediate
      retransfusion.

PMID- 7639380
TI  - Effectiveness of low levels of nonventilated lung continuous positive airway
      pressure in improving arterial oxygenation during one-lung ventilation.
AB  - Continuous positive airway pressure (CPAP) of 5 and 10 cm H2O applied to the
      nonventilated lung is effective in improving arterial oxygenation during one-lung
      ventilation (1-LV). The effectiveness of lower levels of CPAP on improving
      oxygenation, however, has not been reported, possibly because of limitations of
      previous methods of CPAP delivery. Recently, a disposable, self-assembled CPAP
      system capable of delivering CPAP over a wide range of pressures has been
      introduced (Mallinckrodt Medical, Inc., St. Louis, MO). The purpose of this study
      was to evaluate the effectiveness of 2 and 5 cm H2O of CPAP delivered with this
      device in improving PaO2 in thoracic surgical patients during 1-LV. Twenty
      patients scheduled for thoracotomy were anesthetized and a left-sided
      endobronchial tube was placed with fiberoptic bronchoscopic guidance. Patients
      were ventilated with a tidal volume of 12 mL/kg, an FIO2 of 1.0, and the
      respiratory rate was adjusted to maintain PaCO2 at 40 +/- 4 mm Hg. Patients were
      randomized to receive nonventilated lung CPAP at either the 2 (Group I) or 5
      (Group II) cm H2O pressure setting of the device. Application of CPAP followed 20
      min of stable 1-LV in the lateral decubitus position. Compared with two-lung
      ventilation, PaO2 (mean +/- SD) was significantly less with 1-LV (Group I, 126 +/
      75 mm Hg, and Group II, 173 +/- 79 mm Hg). Application of the assigned CPAP
      resulted in an increase in PaO2 compared to 1-LV (Group I, 270 +/- 112 mm Hg, and
      Group II, 386 +/- 66 mm Hg; P < or = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7639381
TI  - Epidural lidocaine delays arousal from isoflurane anesthesia.
AB  - To clarify the effect of epidural lidocaine on arousal from inhaled anesthesia,
      we investigated the minimum alveolar anesthetic concentration at awakening (MAC
      Awake) of isoflurane and the duration between discontinuance of isoflurane
      inhalation and arousal from anesthesia in 60 female abdominal hysterectomy
      patients. All patients received epidural catheterization and were randomly
      assigned to one of five groups. The control group, A, was given normal saline
      intravenously (IV) and epidurally. Group B was given 1 mg/kg of 2% lidocaine IV
      as a bolus. Groups C and D were given 0.5 and 1 mg/kg, respectively, of 2%
      lidocaine IV for 5 min, followed by 30 micrograms.kg-1.min-1. Group E was given 3
      mg/kg of 1.5% lidocaine epidurally as a bolus. These doses of lidocaine or
      control saline were administered 15 min before the end of the surgical procedure.
      MAC-Awake values in Groups A, B, C, D, and E were 0.30% +/- 0.05%, 0.28% +/-
      0.04%, 0.29% +/- 0.04%, 0.31% +/- 0.04%, and 0.18% +/- 0.05% (mean +/- SD),
      respectively. MAC-Awake in Group E was lower than in the other groups (P <
      0.001). The duration until arousal in Group E (21.0 +/- 2.0 min) was longer than
      in Groups A, B, C, and D (12.6 +/- 1.8 min, 12 +/- 2.3 min, 13.3 +/- 2.5 min, and
      14.3 +/- 2.7 min, respectively) (P < 0.001). Plasma lidocaine levels in Groups B,
      C, D, and E were 0.95 +/- 0.17 microgram/mL, 1.07 +/- 0.16 microgram/mL, 2.09 +/-
      0.31 micrograms/mL, and 1.02 +/- 0.16 micrograms/mL, respectively. We conclude
      that analgesia produced by epidural lidocaine delays arousal from isoflurane
      anesthesia. Furthermore, lidocaine plasma levels are shown to be too low to cause
      any sedative effect, thus suggesting that postoperative pain may cause
      significantly faster arousal from anesthesia.

PMID- 7639382
TI  - Changes in heart rate variability under propofol anesthesia: a possible
      explanation for propofol-induced bradycardia.
AB  - We propose to study the bradycardia associated with propofol anesthesia. Ten
      women undergoing laparoscopy for benign disease were studied using ambulatory
      electrocardiogram monitoring. Anesthesia was induced with an intravenous bolus of
      propofol and maintained with an infusion. After ventilation using positive
      pressure via a mask for 5 min, relaxants (succinylcholine or vecuronium) and
      opioids (alfentanil or fentanyl) were administered and the trachea was intubated.
      Approximately 15 min later, the laparoscopic trocar was placed and carbon dioxide
      insufflated. Heart rate variability spectra using a fast Fourier transformation
      technique were determined from the recordings in four separate time periods
      (preinduction, postinduction, postintubation, and posttrocar placement). Total,
      high-frequency, and low-frequency power in each time period was determined.
      Induction of anesthesia with propofol was associated with a significant reduction
      in total, low-frequency, and high-frequency power. Maintenance of anesthesia with
      propofol alone resulted in further reductions in total and low-frequency, but not
      high-frequency, power. Placement of the laparoscopic trocar and insufflation of
      carbon dioxide resulted in a decrease in heart rate and an increase in high
      frequency power. We conclude that high-frequency variability reflects
      parasympathetic tone. Propofol anesthesia reduces parasympathetic tone to a
      lesser degree than sympathetic tone. This autonomic milieu predisposes the
      patient to developing bradycardia in response to parasympathetic stimuli.

PMID- 7639383
TI  - Determination of end-tidal sevoflurane concentration for tracheal intubation and
      minimum alveolar anesthetic concentration in adults.
AB  - The purpose of this study was to determine both the concentration of sevoflurane
      required for tracheal intubation (MACEI) and its minimum alveolar anesthetic
      concentration (MAC) in adults. The study group consisted of 86 elective surgical
      patients, ASA physical status I or II, aged 16-59 yr. There was no premedication
      administered. For MACEI determination, after establishing and maintaining the
      predetermined end-tidal concentration for 20 min, tracheal intubation was
      attempted using a cuffed tracheal tube without muscle relaxant or other
      adjuvants. Each concentration at which tracheal intubation was attempted was
      predetermined as follows: 2.5%, 3.0%, 3.5%, 4.0%, 4.5%, 5.0%, 5.5%, 6.0%, 6.5%,
      and 7.0%. For MAC determination, the patients examined were basically the same as
      those for MACEI determination, except for those who received muscle relaxant or
      other adjuvants because they were "not intubated smoothly." After establishing
      and maintaining the predetermined end-tidal concentration for 20 min, skin
      incision was attempted. Each concentration at which skin incision was attempted
      was predetermined as follows: 0.5%, 1.0%, 1.5%, 2.0%, 2.5%, and 3.0%. The MACEI
      of sevoflurane was 4.52% (95% confidence limits, 3.91%-5.21%), and the ED95 for
      tracheal intubation was 8.07%. The MAC of sevoflurane was 1.58% (95% confidence
      limits, 1.14%-1.98%), and the AD95 (anesthetic ED95) was 2.96%. The MACEI/MAC
      ratio was 2.86 (95% confidence limits, 2.63-3.43). Anesthesia induction followed
      by tracheal intubation can be accomplished in adults when sevoflurane is
      administered as a sole anesthetic, but in excess of 8% end-tidal concentration.

PMID- 7639384
TI  - Transient cardiac standstill associated with embolic phenomena diagnosed by
      intraoperative transesophageal echocardiography during cemented total hip
      arthroplasty.

PMID- 7639386
TI  - Management of difficult intubation caused by lingual tonsillar hyperplasia.

PMID- 7639385
TI  - Bronchospasm after intravenous adenosine administration.

PMID- 7639387
TI  - Another cause of an absent capnogram.

PMID- 7639388
TI  - Blind nasotracheal intubations revisited.

PMID- 7639389
TI  - Calculating the cost of desflurane and propofol: lower costs with lower infusion
      rates.

PMID- 7639390
TI  - Use of ketorolac and fentanyl during outpatient gynecologic surgery: a
      statistical analysis.

PMID- 7639391
TI  - Elimination of 12 and 24 Fr esophageal stethoscopes from anesthetic practice (an
      attempt at cost containment)

PMID- 7639392
TI  - Carotid shunt malposition.

PMID- 7639394
TI  - The magic ball induction.

PMID- 7639393
TI  - Failure of an epidural needle.

PMID- 7639396
TI  - A pitfall in the ventilator circuit leak-check procedure.

PMID- 7639395
TI  - Isoflurane-induced hypotension and vital organ blood flow.

PMID- 7639397
TI  - Adductor pollicis response to ulnar nerve stimulation.

PMID- 7639398
TI  - Usefulness of creatinine clearance.

PMID- 7639399
TI  - Preventing nosocomial tuberculosis--progress at last.

PMID- 7639400
TI  - Nosocomial transmission of multidrug-resistant Mycobacterium tuberculosis.

PMID- 7639401
TI  - Implementing a tuberculosis control program.
AB  - Between January 1989 and December 1990, 26 patients acquired multidrug-resistant
      tuberculosis at our institution. Their exposures occurred when they were admitted
      to a ward where a patient with acid fast bacillus smear-positive pulmonary
      tuberculosis was also admitted. In 20 cases, the infectious patients were not
      isolated until the sputum smears were positive. When the outbreak was recognized
      in the spring of 1990, the infection control department undertook a risk
      assessment and instituted measures that would become the tuberculosis control
      program. Since then, administrative and environmental controls have been
      implemented, education programs are ongoing, personal protective equipment is in
      use, and a more aggressive employee health testing program is underway. The steps
      we took and the barriers we had to overcome to implement our plan are included in
      this article.

PMID- 7639402
TI  - Interrupting transmission from patients with unsuspected tuberculosis: a unique
      role for upper-room ultraviolet air disinfection.

PMID- 7639403
TI  - Respiratory protection devices.
AB  - OSHA authority and responsibility have led to the requirement that health care
      workers potentially exposed to patients with active tuberculosis in situations
      where engineering controls are not feasible for protection must utilize personal
      protective equipment at least equivalent to HEPA respirators. ICPs generally
      believe that this approach is unnecessarily conservative and imposes undue
      burdens on patient care. The arguments on both sides of this controversy have
      some merit. Reported cases of tuberculosis and skin-test conversions among health
      care workers since 1988 and the absence of a demonstrated safe level of exposure
      have led many to the conclusion that HEPA respirators are justified. On the other
      side, tuberculosis currently is not a major problem in some areas of the country,
      and many believe that less stringent personal protective devices (e.g., DM
      respirators) may provide protection equivalent to HEPA filters--at least in terms
      of preventing infection if not in terms of filtration efficiency. They believe
      that the lesser discomfort and lower cost associated with DM respirators justify
      the argument for a more flexible standard. Perhaps additional research can help
      to resolve the remaining controversy. Definitive answers are unlikely to surface
      quickly, however, and it is likely that the controversy and confusion will
      continue for at least awhile longer.

PMID- 7639404
TI  - Efficacy and cost-effectiveness of a needleless intravenous access system.
AB  - BACKGROUND: Needlestick injury has been identified as a major cause of exposure
      to blood and body fluids. The heparin-lock intermittent intravenous procedure was
      implicated in the largest number of needlestick-related exposures (26%) at this
      1100-bed tertiary care hospital, and replacement of this system was imperative.
      Cost concerns, however, necessitated that replacement products not increase
      overall hospital costs. METHODS: A needleless intravenous access system
      (Interlink i.v. Access System; Baxter Healthcare Corp., Parenterals Division,
      Deerfield, Ill.) was introduced. Effectiveness and cost-benefit of this system
      were analyzed by comparing needlestick injuries and their associated costs, as
      well as costs of relevant products and procedures, for the year before
      introduction of the new product with those for 1 year after implementation of the
      new system. RESULTS: During the study period, the needleless access system was
      78.7% effective in reducing intravenous line-related needlestick injuries. There
      was an overall reduction of 43.4% in total needlestick injuries from all
      procedures and events. The incremental cost to this hospital ranged from a 5.3%
      additional cost to a 5.7% savings, without even considering the less quantifiable
      benefits associated with avoidance of needlestick injury, time saved by using
      this product, and decreased infection rate. CONCLUSION: When used as intended,
      this system was extremely effective in reducing intravenous line-related
      needlestick injuries, and the system does pay for itself.

PMID- 7639405
TI  - The effects of circuit and humidifier type on contamination potential during
      mechanical ventilation: a laboratory study.
AB  - BACKGROUND: This study was undertaken because of concerns that ventilator
      humidifiers could be exacerbating the problem of nosocomial pneumonia in patients
      receiving mechanical ventilation. METHODS: Four different brands of humidifiers
      were used in conjunction with a siemens Servo 900B mechanical ventilator (Siemens
      Life Support Services, Solna, Sweden). In the first part, the ventilator was
      operated with humidifiers filled with contaminated water at room temperature. The
      viability of airborne particles and the effect of flow rates on the number of
      particles produced were assessed. In the second part, we measured the effect of
      time and temperature on bacterial survival in humidifier chambers. Because only
      bubble-through humidifiers were determined to produce infectious particles, the
      speed with which a contaminated bubble-through humidifier could infect circuit
      condensate was also determined. Aliquots of chamber water and circuit condensate,
      as well as air samples and distal circuit swabs, were cultured. RESULTS:
      Humidifiers other than bubble-through humidifiers did not produce aerosols.
      Particle production by bubble-through humidifiers varied directly with flow rate
      (R2 = 0.91). Chamber temperatures did not affect chamber colony counts except in
      bubble-through humidifiers. Although chamber colony counts in bubble-through
      humidifiers decreased with time, organisms remained viable throughout the study.
      When bubble-through humidifiers were heated, both condensate and effluent gas
      became heavily contaminated within minutes of flow initiation. CONCLUSIONS:
      Bubble-through humidifiers produce aerosols that readily contaminate both circuit
      condensate and effluent gas. Avoiding bubble-through humidifiers should improve
      patient safety while allowing changes in practice that can result in significant
      cost savings.

PMID- 7639407
TI  - Infection control, human immunodeficiency virus, and home health care: II. Risk
      to the caregiver.

PMID- 7639406
TI  - Training needs of infection control professionals in long-term care facilities in
      Virginia.
AB  - BACKGROUND: Infection control professionals from area long-term care facilities
      contacted us and asked for help in securing infection control training. To
      determine whether there was sufficient statewide need to warrant University
      activity, we conducted a needs assessment. METHOD: An eight-page questionnaire
      was mailed to 220 infection control professionals in nursing homes statewide. The
      instrument focused on training needs and also on training accessibility issues.
      Ninety-nine completed questionnaires were returned for a 41% response rate.
      RESULTS: The infection control professionals who responded came from a
      representative group of long-term care facilities throughout the state. Ninety
      three percent indicated that they were "very interested" or "interested" in a
      series of sessions addressing a wide variety of long-term care infection control
      topics. Ninety-nine percent of the respondents indicated that it was "extremely
      important" or "important" for any such training to focus specifically on long
      term care facilities. CONCLUSIONS: Considerable need for infection control
      training was expressed by infection control professionals in Virginia long-term
      care facilities. Such training must be relevant to long-term care facilities and
      should meet accessibility requirements.

PMID- 7639408
TI  - Recommendations for preventing the spread of vancomycin resistance:
      recommendations of the Hospital Infection Control Practices Advisory Committee
      (HICPAC).
AB  - A rapid increase in the incidence of infection and colonization with vancomycin
      resistant enterococci (VRE) has been reported from U.S. hospitals in the last 5
      years. This increase poses several problems, including a) the lack of available
      antimicrobials for therapy of infections due to VRE, since most VRE are also
      resistant to multiple other drugs, e.g., aminoglycosides and ampicillin,
      previously used for the treatment of infections due to these organisms, and b)
      the possibility that the vancomycin resistance genes present in VRE may be
      transferred to other gram-positive microorganisms such as Staphylococcus aureus.
      An increased risk of VRE infection and colonization has been associated with
      previous vancomycin and/or multi-antimicrobial therapy, severe underlying disease
      or immunosuppression, and intra-abdominal surgery. Because enterococci can be
      found in the normal gastrointestinal or female genital tract, most enterococcal
      infections have been attributed to endogenous sources within the individual
      patient. However, recent reports of outbreaks and endemic infections due to
      enterococci, including VRE, have shown that patient-to-patient transmission of
      the microorganisms can occur either via direct contact or indirectly via hands of
      personnel or contaminated patient-care equipment or environmental
      surfaces.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7639411
TI  - Risk factor profile of nonsmokers with peripheral arterial disease.
AB  - Cigarette smoking is a very common and important risk factor for peripheral
      arterial disease (PAD) such that a history of never having smoked is unusual in
      diseased subjects. The aim of this study was to determine whether never smokers
      with PAD had a unique risk factor profile that put them at particularly high risk
      of disease. The study population was derived from the Edinburgh Artery Study,
      which is a cross-sectional random sample survey of 1592 men and women aged fifty
      five to seventy-four years. PAD was measured by means of the WHO questionnaire on
      intermittent claudication, the ankle brachial pressure index, and a reactive
      hyperemia test. Cigarette smoking was measured by use of a standardized
      questionnaire. In the 561 subjects who had never smoked, 32 (5.7%) had PAD as
      compared with 12.3% in ex-smokers and 17.8% in current smokers. The never smokers
      with disease were slightly older and were more likely to be female than the
      current smokers. They had a higher body mass index, serum cholesterol (non-HDL),
      HDL cholesterol, systolic and diastolic blood pressure, and glucose intolerance,
      although a statistically significant difference (P < 0.01) between never and
      current smokers was found only for body mass index. The risks of disease
      associated with each risk factor were not significantly different. The authors
      conclude that a unique risk factor profile for disease was not apparent among
      subjects who had never smoked, although never smokers were more likely to be
      women and to have higher levels of other risk factors.

PMID- 7639409
TI  - Angiotensin II pressor activity depends on medial and lateral anterior
      hypothalamic pathways.
AB  - The preoptic region of hypothalamus was disconnected from caudal structures with
      two different-size knife cuts in rats to investigate the pathway responsible for
      the effects of intracerebroventricular (ICV) and intravenous (IV) angiotensin II
      (ang II) on blood pressure and arginine vasopressin (AVP) release. Seven days
      after surgery ICV ang II (125 ng) in sham-operated (sham) rats increased mean
      arterial pressure (MAP) (+23 +/- 3 mmHg) and decreased heart rate (HR) (-58 +/- 5
      beats/minute). However, ICV ang II had no effect on MAP or HR of rats with a
      large (preoptic-hypothalamic disconnection) cut. Both the pressor response (+12
      +/- 2 mmHg) and the bradycardia (-39 +/- 6 beats/minute) were significantly
      reduced by a small (medial preoptic-hypothalamic disconnection) cut. The
      increased plasma AVP to ICV ang II in sham rats (9.8 +/- 3.6 pg/mL) was abolished
      in large-cut rats and attenuated in small-cut rats (3.2 +/- 0.7 pg/mL). IV bolus
      injection of ang II (125 ng) in sham rats increased MAP by 43 mmHg, whereas large
      cut rats showed a blunted (25%) pressor response. The pressor response to IV
      infusion of ang II (8 ng/20 microL/minute for 15 minutes) was diminished in large
      cut rats (+4 +/- 1 mmHg) as compared with that in sham rats (+19 +/- 2 mmHg).
      Both cuts transected the projection between the periventricular tissue
      surrounding the anteroventral third ventricle and supraoptic nucleus, but the
      supraoptic-neurohypophyseal pathway was severed only by the large cut.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7639410
TI  - Intrathrombus administration of tissue plasminogen activator in acute
      cerebrovascular occlusion.
AB  - Intraarterial thrombolysis for acute cerebrovascular occlusion has achieved
      recanalization at a 50-90% rate. Clinical outcome has been unpredictable. The
      authors sought to test the hypothesis that intrathrombus administration of
      recombinant tissue plasminogen activator (rt-PA) would improve recanalization
      rate and to assess the possibility that clinical outcome would be predicted by
      the extent of collateral flow. Seven patients with acute cerebrovascular
      occlusion (less than six hours in 6, twenty-four hours in 1) were treated with
      intrathrombus rt-PA at 1 mg/minute. Examinations were scored on a five-point
      motor scale. Collateral flow was assessed angiographically. Vessels recanalized
      in 5 patients, 3 of whom had good outcomes. Vessels failed to recanalize in 2
      patients, 1 of whom had good outcome. Good collateral flow was evident in all 4
      patients with good outcome and in none of those with poor outcome. Intrathrombus
      administration of rt-PA is technically feasible. Favorable clinical outcome is
      more likely in the presence of good collateral flow. In the absence of good
      collateral flow, ultra-early intervention may be necessary.

PMID- 7639412
TI  - In vivo ultrasonic parametric imaging of carotid atherosclerotic plaque by
      videodensitometric technique.
AB  - Extensive experimental and clinical data show that the ultrasonic image conveys
      information on the biochemical composition of the atherosclerotic plaque, ie, the
      relative content of lipids (hypoechoic), fibrous tissue (hyperechoic), and
      calcific deposits (very echogenic with shadowing). A more dishomogeneous echo
      structure of the plaque is also more often associated with clinically complicated
      carotid plaques. To date, however, the assessment of plaque density and
      homogeneity by transcutaneous B-mode imaging remains subjective and qualitative.
      The aim of this study was to assess whether plaque echodensity and homogeneity
      might be established on a more objective and quantitative basis by description of
      the spatial distribution of echo amplitude (referred to as tissue texture)
      applied to digitized images, obtained with commercially available B-mode
      transcutaneous imaging systems. A total of 47 B-mode images derived from
      echotomographic studies in 10 patients were digitized off line. For each region
      of interest, a set of first-order (mean gray level, standard deviation, skewness,
      kurtosis: mathematical descriptors of the shape of the frequency distribution of
      gray-level histogram) and of second-order (entropy, angular moment: mathematical
      descriptors of the spatial distribution of gray levels within the region of
      interest) textural parameters were evaluated. The visual, concordant reading by
      two independent, experienced observers assigned the plaques on the basis of
      qualitatively assessed echodensity to three groups: "soft" (n = 18), "fibrotic"
      (n = 20), "calcific" (n = 9). Regarding spatial gray-level distribution, 46
      plaques would be separated into "homogenous" (n = 17) and "dishomogeneous" (n =
      29). On digitized images, the normalized mean gray level was the most effective
      first-order textural parameter for distinguishing soft (24.2 +/- 12.4 arbitrary
      units in a zero to 255 scale) from fibrotic (64.5 +/- 16.4) and calcific plaques
      (125.3 +/- 24.5), P < 0.01 for all intergroup differences. "Homogeneous" plaques
      were separated from "heterogeneous" ones on the basis of entropy (5 +/- 1 vs 7.9
      +/- 9.7; P < 0.01), whereas the values of angular second moment overlapped
      (1.542E-3 + 1.334E-3 vs 5.181E-4 +/- 2.5615E-4, P = ns). In conclusion,
      quantitative texture analysis of ultrasonic images derived from transcutaneous,
      high-resolution, commercially available B-scan systems is feasible in man and
      provides a quantitative operator-independent assessment of plaque echodensity and
      homogeneity.

PMID- 7639413
TI  - Heart rate-corrected ankle-to-arm index in the diagnosis of moderate lower
      extremity arterial disease.
AB  - Although the ratio of ankle-to-arm systolic pressures (AAI) at rest is widely
      used in the clinical diagnosis of peripheral arterial disease, the heart rate
      (HR) at which the measurements are performed is rarely reported. The relation of
      ankle-to-arm index (AAI) to HR was studied in a normal population (n = 65) and in
      a population of patients (n = 101) suspected of moderate lower extremity arterial
      disease (LEAD). In the normal population, a significant inverse correlation was
      found between AAI and HR at rest: AAI = -0.277 x HR/100 + 1.303; r = -0.52, P <
      0.001. In the second population suspected of LEAD, the authors recorded AAI and
      HR at rest on both legs; 80 normal legs, 110 diseased legs. Thereafter, with
      normal limits as superior to 0.8, 0.9, and 0.95, sensitivity was respectively 16,
      39, and 46%, and specificity was 100, 100, and 98%. In defining normal limit as
      superior to -2 standard deviations of the AAI-HR relation found in the normal
      population, sensitivity and specificity were 57 and 100%, respectively. IN
      CONCLUSION: In screening for LEAD in the general population with the use of AAI
      at rest, the authors suggest that the heart rate at which arterial pressure
      measurements are performed should be reported.

PMID- 7639414
TI  - Coronary artery aneurysms develop in weanling rabbits with serum sickness but not
      in mature rabbits. An experimental model for Kawasaki disease in humans.
AB  - The involvement of the cardiovascular system in rabbits with serum sickness is
      similar of that in Kawasaki disease, both with respect to the histologic changes
      of the myocardium, the valves, the coronary arteries, and the aorta and to the
      sequence with which they appear. Although coronary arteritis appears the same
      histologically, aneurysms did not occur in mature rabbits, even in case of
      necrosis of an arterial segment with deletion of muscle and elastic tissue. On
      the other hand, weanling rabbits with serum sickness had a tendency to develop
      aneurysms of coronary arteries, despite little cellular infiltration and reactive
      fibrocellular hyperplasia. The age factor thus appears to play an important role
      in the development of coronary aneurysms in Kawasaki disease, irrespective of the
      underlying mechanism, be it a markedly increased permeability to mediators
      through degenerated endothelial cells, or primary degenerated muscle cells with
      marked thinning of the media without much inflammatory cellular reaction.
      Furthermore, this study provides an insight into the long-term prognosis of
      transient dilatation of coronary arteries in the acute stage of Kawasaki disease.

PMID- 7639415
TI  - Transcutaneous oxygen tension and Doppler ankle pressure during upper and lower
      body exercise in patients with peripheral arterial occlusive disease.
AB  - The effects of upper and lower body exercise on blood supply to the lower
      extremities were investigated in patients with peripheral arterial occlusive
      disease (PAOD) by measurements of transcutaneous oxygen tension (tcPO2) and
      Doppler ankle pressure (DAP). Twenty patients with PAOD (PAOD group) and 10
      subjects without PAOD (control group) performed treadmill test (TT), recumbent
      cycle ergometry (CE), and rowing ergometry (RE) with a fixed seat. The tcPO2 was
      registered on the calf and DAP was measured at the end of each step of CE and RE.
      The walking distance in TT of the control group was not limited (> 1000 m),
      whereas that of the PAOD group was 161 m in median. In the control group there
      was no significant difference of performance between CE (125 +/- 33 W) and RE
      (111 +/- 24 W), whereas in the PAOD group, performance was lower in CE (72 +/- 31
      W) than in RE (102 +/- 28 W) (P < 0.01). DAP of controls increased during both CE
      (136 to 165 mmHg) and RE (170 to 213 mmHg), whereas the DAP of the PAOD group
      decreased during CE (from 85 to 44 mmHg) and remained relatively constant during
      RE (113 to 101 mmHg). In controls, tcPO2 did not distinctly change during TT (70
      to 66 mmHg) and increased during CE (58 to 73 mmHg) and RE (69 to 82 mmHg),
      whereas in the PAOD group, tcPO2 decreased during TT (66 to 33 mmHg) and CE (50
      to 22 mmHg) and remained almost unchanged in RE (64 to 60 mmHg). A hyperbolic
      relationship was found between tcPO2 and DAP. In conclusion, during upper body
      exercise, blood supply to the lower extremities in patients with PAOD was not
      affected, whereas lower body exercise led to exhaustion of the functional reserve
      of blood supply. Because of a hyperbolic relationship between tcPO2 and DAP,
      tcPO2 remained relatively constant if blood supply was sufficient, but in
      disturbed blood supply a small change of DAP was accompanied by a great change of
      tcPO2. Therefore, in critical ischemia the change of tcPO2 was more sensitive
      than that of DAP.

PMID- 7639416
TI  - Efficacy of Ibudilast on lower limb circulation of diabetic patients with
      minimally impaired baseline flow: a study using color Doppler ultrasonography and
      laser Doppler flowmetry.
AB  - Ibudilast is a prostacyclin-mediated vasodilator and antiplatelet agent. The
      hemodynamic effects of ibudilast were evaluated in 41 patients with non-insulin
      dependent diabetes mellitus by means of two-dimensional Doppler ultrasonography
      and laser Doppler blood flowmetry. Before and one hour after oral administration
      of ibudilast (10 mg), or elastase (1800 U) as a control, the cross-sectional area
      (CSA) of the dorsal pedis artery, its blood flow index (BFI), and dermal
      microcirculatory blood volume (MBV) were measured. In the ibudilast group, all of
      the parameters (CSA, BFI, and MBV) significantly increased as compared with the
      elastase group. These data suggest that ibudilast is effective in ameliorating
      diabetic macroangiopathy and microangiopathy of the lower limbs.

PMID- 7639417
TI  - L-propionylcarnitine effect on postexercise and postischemic hyperemia in
      patients affected by peripheral vascular disease.
AB  - The hemodynamic effect of L-propionylcarnitine (LPC) administered intravenously
      was evaluated in a double-blind, randomized, three-period crossover study in 12
      men (aged sixty to seventy-five years) with Leriche-Fontaine stage II peripheral
      arterial disease of lower limbs. At baseline, maximum working capacity of each
      patient was determined by a standardized ergometric test. This test was repeated
      at 80% of each patient's maximum working capacity before and after intravenous
      administration of LPC. Each patient received three single doses of 300 mg, 600
      mg, and 1200 mg of LPC with a two-day rest period between them. Hemodynamic
      variables measured by strain-gauge plethysmography were: peak blood flow, peak
      flow time, and halftime and total time of hyperemia both after exercise and after
      induction of ischemia (with an occlusion cuff). LPC administration significantly
      shortened the halftime as well as the total time of hyperemia after exercise and
      after ischemia. With the two highest doses, LPC shortened the peak flow time
      after exercise. The peak blood flow after exercise and after ischemia increased,
      but this increase did not reach statistical significance. The results obtained
      indicate that LPC improves circulatory reserve of the ischemic limb and has no
      effect on heart rate and arterial blood pressure. No adverse events were
      reported. The effect of LPC on the hyperemic response to stress, mainly on
      halftime of hyperemia, is possibly due to a drug-induced increase of adenosine
      triphosphate utilization by the ischemic tissues.

PMID- 7639418
TI  - The effect of ageing on platelet function and fibrinolytic activity.
AB  - Twelve healthy male volunteers, mean age twenty-five, range twenty-one to thirty
      years, and 12 healthy middle-aged male volunteers mean age fifty-eight, range
      forty-four to seventy-two years, were tested regarding platelet aggregation
      induced by adenosine diphosphate and fibrinolytic activity, estimated as
      euglobulin clot lysis time (ECLT), tissue plasminogen activator (t-PA), and the
      fast-acting inhibitor against t-PA normally referred to as (PAI-1). Platelet
      aggregation increased significantly in the middle-aged group as compared with the
      young, as shown by a decrease in ADP thresholds for irreversible aggregation (P <
      0.01). In healthy young volunteers, vigorous cycling exercise by itself caused
      platelet aggregability to decrease (P < 0.05). Such changes were not observed in
      the elderly. Fibrinolytic activity decreased significantly in the middle-aged
      group as shown by a prolongation of the ECLT (P < 0.01) and PAI-1, although not
      significantly, increased by approximately 100%, whereas t-PA significantly
      increased in the middle-aged group (P < 0.01). The present results suggest that
      increasing age is associated with not only increased platelet aggregability but
      also decreased fibrinolytic activity.

PMID- 7639419
TI  - Relation of hematocrit values to coronary heart disease, arterial hypertension,
      and respiratory impairment in occupational and population groups of the Athens
      area.
AB  - Hematocrit values (Hct) were studied in relation to clinical and
      electrocardiographic (ECG) manifestations of coronary heart disease (CHD),
      arterial hypertension (AH), and respiratory impairment (RI) in 2901 adults (2033
      men, 868 women) thirty to seventy years old, who comprised selected groups of
      large occupational (8611 workers) and population (5573 individuals) samples of
      the Athens area. The results of this study were as follows: 1. The women of the
      population sample with high Hct values had a significantly greater frequency of
      CHD (14.6%) as compared with women of the same sample with low Hct values (7.4%)
      (chi 2 = 12.778 P < 0.005). 2. Subjects of both sexes in the population sample
      with high Hct values had significantly higher mean levels of systolic and
      diastolic blood pressure as compared with subjects of the same population sample
      with low Hct values (F:4.61, P < 0.01). 3. In the women of the population sample
      with RI, the mean Hct values were significantly higher than those in the normal
      population (t:1.994, P < 0.05). It is concluded that high Hct values as an
      indirect measure of increased blood viscosity seem to be related to CHD and AH.
      Moreover, RI is correlated with high Hct values.

PMID- 7639420
TI  - Does increased lipoprotein (a) impair the effectiveness of thrombolysis with
      streptokinase?
AB  - Although lipoprotein (a) [Lp(a)] has been shown to interfere with thrombolysis in
      vitro, its effects on thrombolytic therapy in patients with acute myocardial
      infarction (MI) are not clear. The authors evaluated 32 male patients ages thirty
      five to seventy-five (mean fifty-two +/- ten) with the diagnosis of acute MI who
      underwent thrombolytic therapy with 1,500,000 units of intravenous streptokinase.
      All patients underwent coronary angiography within seven days of the infarction
      from which the thrombolysis in myocardial infarction (TIMI) flow grades of the
      infarct-related artery, coronary scores, and ejection fraction were determined.
      Anterior MI was found in 19 patients (59.4%), inferior MI in 12 (37.5%), and
      posterolateral MI in 1 patient (3.1%). They found that 6 patients (18.8%) had
      TIMI flow 0 to 1, and 26 patients (81.2%) had TIMI flow grade 2 or 3. The Lp(a)
      levels ranged from 0.1 to 60 mg/dL with a mean of 8.6 +/- 17 mg/dL. Eight (25%)
      of the patients had Lp(a) levels above 30 mg/dL. The TIMI flow rates were not
      found to be lower in patients with high Lp(a) levels (P > 0.05), and there was no
      significant correlation between the TIMI flow rates and the Lp(a) levels (r =
      0.28). There was a good correlation between coronary scores and Lp(a) levels (r =
      0.87). They conclude that although there is a good correlation between the extent
      of coronary atherosclerosis and Lp(a) levels, Lp(a) is not a strong predictor of
      the outcome of thrombolytic therapy.

PMID- 7639421
TI  - Transthoracic visualization of pulmonary thrombus that mimicked left atrial
      thrombus. A case report.
AB  - A forty-five-year-old woman with an unusual case of primary pulmonary
      hypertension is presented. She showed a progressive dilatation of the pulmonary
      arteries and pulmonary thrombus over twenty-one years. Transthoracic
      echocardiography showed the presence of pulmonary arterial thrombus that mimicked
      left atrial thrombus. However, when the transducer was rotated clockwise to
      obtain the short-axis view, a thrombus was observed in the right pulmonary artery
      with spontaneous echo contrast. Although the visualization of pulmonary arterial
      thrombus by echocardiography has been quite limited, it would be worthwhile since
      patients with primary pulmonary hypertension may have enlarged pulmonary
      arteries, as observed in the present case.

PMID- 7639422
TI  - Pseudo-alternans of left ventricular end diastolic pressure. A case report.
AB  - The authors report a case of left ventricular end diastolic pressure alternans
      without systolic alternans in a patient with bradycardia and tachypnea. This is
      an artifact due to the heart rate falling in a 2:1 ratio to the respiratory
      cycle. Alternation of left ventricular end diastolic pressure should be
      interpreted carefully in patients with bradycardia.

PMID- 7639423
TI  - Coronary artery disease in dermatomyositis. A case report.
AB  - A sixty-two-year-old woman with chronic dermatomyositis (DM) receiving steroid
      monotherapy developed coronary artery stenosis. She had lung fibrosis and
      complained of dyspnea, but no ischemia was suggested by electrocardiogram.
      Ateriographic findings and clinical symptoms of coronary artery disease in DM
      have not been previously reported.

PMID- 7639424
TI  - Nonocclusive ischemic colitis following glycerin enema in a patient with coronary
      artery disease. A case report.
AB  - Acute colonic ischemia is the most common form of intestinal ischemia.
      Nonocclusive ischemic colitis contributes to some of these disorders. Heart
      disease, such as congestive heart failure, myocardial infarction, arrhythmias,
      aortic valve disease, and atherosclerotic cardiovascular disease, account for
      many of its risk factors. The majority of cases are associated with severe
      congestive heart failure with low cardiac output, or disease states resulting in
      dehydration, or the splanchnic vasoconstrictive effect of some medications.
      Reactive splanchnic vasoconstriction is responsible for nonocclusive ischemic
      colitis. Ischemic colitis induced by a cleansing enema has been reported once
      before. The authors present a case of coronary artery disease complicated by
      colonic ischemia following glycerin enema in preparation for coronary bypass
      surgery. Reactive inferior mesenteric artery spasm in response to the enema was
      noted in this case, rather than diffuse mesenteric artery spasm in response to
      low cardiac output state and vasoconstrictive drugs.

PMID- 7639425
TI  - Left coronary sinus of Valsalva aneurysm: an extremely rare malformation. A case
      report.
AB  - The authors describe a sixty-four-year-old man who underwent coronary angiography
      for angina pectoris and was found to have a left coronary sinus aneurysm--an
      extremely rare malformation.

PMID- 7639426
TI  - Orthodontists needed on the implant team.

PMID- 7639427
TI  - The CR-CO interchange.

PMID- 7639428
TI  - CR-CO study well done.

PMID- 7639429
TI  - Purpose of CR-CO study clear.

PMID- 7639430
TI  - Use of maxillary intraosseous implants for Class II elastic anchorage.

PMID- 7639431
TI  - The extraction-nonextraction dilemma as it relates to TMD.
AB  - Extraction has been a controversial subject for as long as the specialty of
      orthodontics has existed. Some authors believe that the extraction of premolars
      leads to temporomandibular disorders. This occurs, they say, because the vertical
      dimension collapses. Concomitantly, over-retraction and retroclination of the
      incisors cause the facial profile to flatten, bring about premature anterior
      contacts, and distally displace the mandible and mandibular condyle. Numerous
      correlation studies in the dental literature do not support this contention.
      There appears to be no higher incidence of temporomandibular disorders in
      patients treated with the extraction of premolars than in nontreated patients or
      those treated without extractions. Analysis of premolar extraction cases reveals
      that there is no collapse of the vertical dimension; on the contrary, the
      vertical dimension is either maintained or slightly opened. Similarly, there is
      no evidence that premolar extraction causes undesirable flattening of the facial
      profile. The facial profile established during treatment is primarily the result
      of diagnosis and treatment mechanics. Excessive anterior interferences resulting
      in possible posterior condyle displacement are the result of treatment mechanics.
      When arches are leveled properly and space closure and overjet reduction are
      adequately controlled, there is no reason that such interferences should occur.

PMID- 7639432
TI  - An analytical evaluation of a new spring design for segmented space closure.
AB  - Contemporary segmented-arch space-closure springs require activation techniques
      that have the side effect of producing a significant amount of geometric
      nonlinearity. This nonlinearity makes these springs difficult to manipulate
      because it allows tipping during space closure which may be considered adverse. A
      new spring mechanism has been designed in response to these difficulties so that
      the advantages of the segmented-arch technique can be extended to those
      clinicians presently using simple sliding mechanics as a means of space closure.
      This spring mechanism has eliminated a significant portion of the geometric
      nonlinearity by using force-application devices (activators) such as elastics or
      coil springs as the means of activation. By selecting the right activator it may
      be possible to close an entire extraction site (approx. 7 mm) with one
      activation. The proposed mechanism essentially consists of two units: an
      anchorage unit (M/F = 18 mm), and a translational unit (M/F = 11 mm). These units
      are combined in order to achieve anterior retraction, posterior protraction, or a
      combination of the two, which is termed reciprocal-attraction. The finite-element
      method was used in place of bench studies to test the new spring design. The
      commonly used reciprocal-attraction spring tested with a nearly constant M/F
      ratio equal to 11 +/- 1 mm over an effective force range of 50 gm to 450 gm. The
      results from the other two tests also showed that precisely controlled couple-to
      force (M/F) ratios can be maintained over a wide range of effective forces.

PMID- 7639433
TI  - Initial tooth movement under extraoral force and considerations for controlled
      molar movement.
AB  - Initial movement of the maxillary first molars under the application of straight
      pull, cervical-pull, and high-pull headgear was measured in human subjects.
      Facebow deflection can influence molar movement as the relationship of the force
      vector to the molar's center of resistance changes with an increase of force. The
      present study proposes using headgear with a combination of variable-pull headcap
      and short outer bow. A variable-pull headcap allows a great range in force
      direction. The direction of the headgear force system can be accurately
      determined using a short outer bow.

PMID- 7639434
TI  - Orthodontic resin under water immersion.
AB  - The absorption and desorption of water by a polymer matrix of composite
      orthodontic resin could cause debonding of the filler-matrix or hydrolytic
      degradation of fillers and loss of bond strength. In this study, the bond
      strength of brackets directly bonded with orthodontic composite to the enamel
      surface of premolars was measured with an Instron machine; the debonding
      interface distribution was analyzed by scanning electron microscope and energy
      dispersive x-ray spectrometry following water immersion for 1, 2, and 3 days, and
      1, 2, 4, 8, 16, 24, and 32 weeks, respectively. The results show that, under
      water immersion, bond strength may gradually weaken over time. The greatest loss
      occurs initially, followed by a period of relative stabilization, and then a
      weaker reduction after 24 weeks. The greater the time in water immersion, the
      less the bond strength and the greater the destruction of the composite resin.
      The debonding interface occurs between bracket and resin.

PMID- 7639435
TI  - The role of intercuspation in the regulation of transverse maxillary development
      in Macaca fascicularis.
AB  - The role of intercuspation of the teeth in transverse maxillary growth and dental
      arch development was investigated radiographically with the aid of implants in
      Macaca fascicularis monkeys. Fourteen animals were randomly allocated to a
      control group (n = 7) and an experimental group (n = 7) and were followed from 29
      to 100 weeks of age. Intercuspation was eliminated in the experimental group by
      grinding the canines and molar cusps in both dental arches as soon as possible
      after emergence. Maxillary occlusal radiographs were taken at regular intervals.
      Linear and angular analyses of skeletal changes revealed that midpalatal sutural
      growth seems to be independent of intercuspation. The developing dental arch,
      however, showed a significantly greater increase in width in certain areas in the
      experimental group than in the control group. Most findings support the
      hypothesis that the width of the maxillary dental arch is guided by the width of
      the mandible through the intercuspation of the posterior teeth.

PMID- 7639436
TI  - F-H to AB plane angle (FABA) for assessment of anteroposterior jaw relationships.
AB  - The horizontal relationship of the jaws has been defined as the angles or
      distances between the reference planes of the craniofacial complex and points A
      and B, which are representative of the anterior limits of the denture bases. The
      aims of this study were (1) to examine statistically and geometrically the
      different cephalometric measurements which are used to indicate the A-P jaw
      relationship, and (2) to provide a more reliable parameter by means of
      comparative cephalometric analyses with various clinical examples. The APDI and
      Wits appraisal are parameters for evaluating the anteroposterior relationship of
      the dentition rather than the jaws. FH to AB plane angle (FABA) may provide not
      only a reliable cephalometric measurement of the anteroposterior relationship of
      the jaws but also a clue to the facial profile.

PMID- 7639437
TI  - Method for quantifying facial asymmetry in three dimensions using
      stereophotogrammetry.
AB  - A three-dimensional method to quantify facial asymmetry is introduced.
      Stereophotogrammetry was applied to determine three-dimensional (3-D) coordinates
      for eight pairs of surface landmarks of 106 individuals, including 16 with an
      operated complete unilateral cleft lip and palate. Facial asymmetry was
      quantified from four different reference planes that were defined perpendicular
      to and bisecting lines between pairs of bilateral landmarks related to the eyes,
      nose and mouth. Significant differences (P < 0.01) between these four planes were
      determined using multivariate analyses of variance (MANOVA). It is concluded that
      the best reference plane to select in studies of facial asymmetry is formed by
      the one which is perpendicular to and bisects the line that connects the
      landmarks Exocanthion. Reproducibility and validity of the method is
      demonstrated.

PMID- 7639438
TI  - Treatment of postmenopausal osteoporosis with slow-release sodium fluoride. Final
      report of a randomized controlled trial.
AB  - OBJECTIVE: To test whether slow-release sodium fluoride inhibits spinal fractures
      and is safe to use. DESIGN: Placebo-controlled randomized trial. INTERVENTIONS:
      Slow-release sodium fluoride, 25 mg twice daily, in four 14-month cycles (12
      months receiving sodium fluoride followed by 2 months not receiving it) compared
      with placebo. Calcium citrate, 400 mg calcium twice daily, continuously in both
      groups. PATIENTS: 48 of 54 patients who received sodium fluoride and 51 of 56
      patients who received placebo completed at least 1 year of the study. All
      patients had postmenopausal osteoporosis. RESULTS: Compared with the placebo
      group, the fluoride group had a lower individual vertebral fracture rate (0.064
      +/- 0.182 per patient-year compared with 0.205 +/- 0.297 per patient-year; P =
      0.002), a higher unadjusted fracture-free rate (85.4% compared with 56.9%; P =
      0.001), and a greater survival estimate (relative risk, 0.3 [95% CI, 0.12 to
      0.76]) for new fractures. The recurrent spinal fracture rate did not differ
      between the two groups. The fluoride group had a substantial increase in L2-L4
      bone mass of 4% to 5% per year for 4 years, a mean increase in femoral neck bone
      density of 2.38% +/- 3.33% per year, and no change in radial shaft bone density.
      The frequency with which minor side effects and appendicular fractures occurred
      was similar in the two groups; no patients developed microfractures or gastric
      ulcers. CONCLUSION: Slow-release sodium fluoride and calcium citrate administered
      for 4 years inhibits new vertebral fractures (but not recurrent fractures),
      augments spinal and femoral neck bone mass, and is safe to use.

PMID- 7639439
TI  - The first reported outbreak of diarrheal illness associated with Cyclospora in
      the United States.
AB  - OBJECTIVE: To investigate and characterize the epidemiology of a diarrheal
      outbreak associated with a potentially new pathogen, Cyclospora species
      (previously referred to as Cyanobacteria [blue-green algae]-like bodies). DESIGN:
      Three retrospective cohort studies supported by laboratory studies, environmental
      investigation, and community surveillance. SETTING: A hospital in Chicago.
      PARTICIPANTS: Housestaff physicians and hospital administrative staff.
      MEASUREMENTS: Identification of clinical features associated with illness and
      potential risks for acquisition of infection. RESULTS: Illness was characterized
      by watery diarrhea, abdominal cramping, decreased appetite, and low-grade fever.
      Symptoms typically occurred in a distinctive cycle of remissions and
      exacerbations lasting up to several weeks. Stool cultures and examinations for
      known ova and parasites were negative. Microscopic examination of stool specimens
      from 11 ill persons showed many spherical bodies, 8 to 10 microns in diameter,
      that were identified as Cyclospora organisms. The organisms disappeared by 9
      weeks after onset of illness in the 7 patients from whom follow-up specimens were
      obtained. Epidemiologic studies implicated tap water from a physicians' dormitory
      as the most likely source of the outbreak. Environmental investigation suggested
      that stagnant water in a storage tank may have contaminated the water supply
      after a pump failure. CONCLUSIONS: This is the first reported outbreak of
      diarrhea associated with Cyclospora in the United States. Cyclospora may be a
      human enteric pathogen able to produce bouts of acute and relapsing diarrhea, and
      it should be considered in assessments of patients with unexplained, prolonged
      diarrheal illness.

PMID- 7639440
TI  - Risk factors for group B streptococcal disease in adults.
AB  - OBJECTIVE: To determine risk factors for community-acquired and nosocomial group
      B streptococcal disease in adults. DESIGN: Case-control study. SETTING: 3
      metropolitan areas in the United States with an aggregate population of 6.6
      million persons. PATIENTS: 219 nonpregnant adults with invasive group B
      streptococcal infection identified by a population-based surveillance in 1991 and
      1992 and 645 hospital-matched controls. RESULTS: The following conditions were
      associated with a significantly increased risk for community-acquired group B
      streptococcal infection after controlling for age in multivariate analysis:
      cirrhosis (odds ratio, 9.7 [95% CI, 3.5 to 26.9]; P < 0.001), diabetes (odds
      ratio, 3.0 [CI, 1.9 to 4.7]; P < 0.001), stroke (odds ratio, 3.5 [CI, 1.9 to
      6.4]; P < 0.001), breast cancer (odds ratio, 4.0 [CI, 1.6 to 9.8]; P = 0.002),
      decubitus ulcer (odd ratio, 4.0 [CI, 1.6 to 9.8]; P = 0.002), and neurogenic
      bladder (odds ratio, 4.6 [CI, 1.4 to 15.1]; P = 0.01). Sixty-three percent of
      community case-patients had at least one of these conditions. Nosocomial
      infection (48 cases [22%]) was independently associated with the placement of a
      central venous line (odds ratio, 30.9 [CI, 5.2 to 184.1]; P < 0.001), diabetes,
      congestive heart failure, and seizure disorder. CONCLUSIONS: Several chronic
      conditions were independently associated with group B streptococcal disease, and
      most case-patients had at least one of these conditions. If group B streptococcal
      vaccines being developed for prevention of neonatal disease are protective in
      adults, a vaccination strategy targeting those at highest risk has the potential
      to substantially reduce the burden of invasive group B streptococcal infection in
      adults.

PMID- 7639441
TI  - Relapsing invasive group B streptococcal infection in adults.
AB  - OBJECTIVE: To study recurrent group B streptococcal infection in adults. DESIGN:
      Patients with more than one reported group B streptococcal infection were
      identified through active surveillance for this infection. Sterile-site group B
      streptococcal isolates were evaluated for serotype and molecular subtyping using
      restriction endonuclease analysis of chromosomal DNA (REAC). SETTING: All acute
      care hospitals in Maryland. PATIENTS: Nonpregnant residents of Maryland 18 years
      of age or older. RESULTS: 22 adults had at least two group B streptococcal
      episodes that were separated by 2 to 95 weeks (mean, 24 weeks). Of 395 patients
      with invasive group B streptococcal infection who survived the first episode and
      were followed for at least 1 year, 17 (4.3% [95% CI, 2.6% to 6.9%]) had more than
      one episode. Several patients were found to have endocarditis or osteomyelitis
      during the second episode. Group B streptococcal isolates from both episodes were
      obtained from 18 of 22 patients. Of the 18 isolate pairs, 13 (72% [CI, 46% to
      90%]) had identical REAC patterns; the probability that at least 13 matches would
      be found by chance alone was less than 0.000001. Among patients with recurrent
      infection caused by the same strain, the interval between episodes was shorter
      (mean, 14 weeks) than that among patients with recurrent infection caused by
      another strain (mean, 43 weeks; P = 0.05). CONCLUSIONS: Recurrent group B
      streptococcal infection is common among adults and in most cases appears to be
      caused by relapse. The optimal management of adults with a first episode of group
      B streptococcal infection needs to be further defined to minimize the likelihood
      of recurrent disease.

PMID- 7639442
TI  - Long-term follow-up of adults with acute lymphoblastic leukemia in first
      remission treated with chemotherapy or bone marrow transplantation. The Acute
      Lymphoblastic Leukemia Working Committee.
AB  - OBJECTIVE: To determine whether the conclusions of a 1991 study, which showed
      that adults with acute lymphoblastic leukemia in first remission had similar
      leukemia-free survival rates when treated with chemotherapy or HLA-identical
      sibling bone marrow transplantation, remain valid after more than 4 years of
      additional follow-up. DESIGN: Retrospective comparison of two cohorts of patients
      using left-truncated Cox regression to adjust for differences in baseline
      characteristics and time to treatment. SETTING AND PATIENTS: Chemotherapy
      recipients were 484 consecutive patients with acute lymphoblastic leukemia in
      first remission treated in 44 hospitals in Germany that were participating in two
      consecutive trials of the German Acute Lymphoblastic Leukemia Therapy Trials
      Group. Transplant recipients were 234 consecutive recipients of HLA-identical
      sibling bone marrow transplants for acute lymphoblastic leukemia in first
      remission in 98 centers, worldwide, reporting data to the International Bone
      Marrow Transplant Registry. INTERVENTIONS: Intensive combination chemotherapy or
      HLA-identical sibling bone marrow transplantation preceded by high-dose
      chemotherapy with or without total body irradiation. MEASUREMENTS: Relapse,
      treatment-related mortality, and leukemia-free survival rate 9 years after first
      complete remission. RESULTS: The conclusions of our previous analyses were
      confirmed. Actuarial relapse probabilities at 9 years were 66% (95% CI, 61% to
      70%) for chemotherapy and 30% (CI, 22% to 37%) for transplantation (P < 0.0001).
      The leukemia-free survival rates at 9 years were 32% (CI, 27% to 37%) for
      chemotherapy and 34% (CI, 28% to 40%) for transplantation (P > 0.02).
      CONCLUSIONS: Fewer relapses but more treatment-related deaths were seen with
      transplantation than with chemotherapy. Thus, leukemia-free survival rates were
      similar in adults receiving transplantation and adults receiving chemotherapy for
      acute lymphoblastic leukemia in first remission.

PMID- 7639443
TI  - Syncope mediated by posturally induced ventricular tachycardia.

PMID- 7639444
TI  - Pressure ulcers in the nursing home.
AB  - OBJECTIVE: To review the literature on the causes, epidemiology, prevention, and
      treatment of pressure ulcers in nursing homes and to summarize this information
      for clinicians caring for nursing home residents. DATA SOURCES: A MEDLINE search
      of English-language articles published between 1980 and October 1994 using the
      terms decubitus ulcer and elderly. References from identified articles were also
      examined. STUDY SELECTION: Articles were excluded if the title indicated that
      patients were not nursing home residents (unless data from nursing homes were
      limited or unavailable), that patients were not elderly, or that the ulcers were
      related to peripheral vascular disease or neuropathy. DATA EXTRACTION: Selected
      studies either contained original data or were meta-analyses. Prevalence studies
      were required to have an identifiable denominator; risk factor and incidence
      studies were required to have an identifiable cohort and a specified duration of
      follow-up. Preference was given to risk factors identified through multivariate
      analyses. Studies of preventive and therapeutic interventions were required to
      have an identifiable control group; preference was given to randomized controlled
      trials. DATA SYNTHESIS: Seventeen percent to 35% of patients have pressure ulcers
      at the time of admission to a nursing home, and the prevalence of pressure ulcers
      among nursing home residents ranges from 7% to 23%. Among high-risk patients, the
      incidence of pressure ulcers is estimated to be 14/1000 patient-days. Residents
      at higher risk for developing ulcers are those who have limited ability to
      reposition themselves, cannot sense the need to reposition, have fecal
      incontinence, or cannot feed themselves. Occlusive dressings are as effective and
      less costly than traditional wet-to-dry saline dressings for treating earlier
      stages of pressure ulcers. There is no consensus on the use of specialized beds
      in the nursing home for promoting the healing of advanced-stage ulcers or for
      reducing the incidence of ulcers in high-risk patients. Specific interventions
      should not detract from careful, total assessment and management of the patient.
      CONCLUSIONS: Pressure ulcers in the nursing home are common problems associated
      with significant morbidity and mortality. Because resident characteristics can
      identify residents likely to develop ulcers, preventive measures can be
      implemented early. Therapy for advanced stages of pressure ulcers is expensive
      and prolonged. Involvement of the physician with the multidisciplinary nursing
      home team is essential for prevention and therapy.

PMID- 7639445
TI  - Expanding indications for permanent pacemakers.
AB  - PURPOSE: To review the current clinical experience with new and expanding
      indications for permanent cardiac pacing. DATA SOURCES: A MEDLINE search was done
      of the English-language literature published from 1980 through 1994 about
      indications for permanent pacing. Five major areas were identified and searched:
      cardiomyopathies, atrial fibrillation, the long QT syndrome, cardiac
      transplantation, and vasovagal syncope. A manual search was then done for other
      contributions, including abstracts. STUDY SELECTION: Because published reports in
      these areas are scarce, all of the peer-reviewed articles and most of the
      relevant abstracts found were reviewed. DATA EXTRACTION: Data were manually
      extracted from the various sources, and the reports were classified and
      summarized according to specific indications. RESULTS: Pacing is becoming an
      important option in the treatment of patients with symptomatic drug-resistant
      hypertrophic obstructive cardiomyopathy. Symptomatic and hemodynamic benefits
      have been shown in patients with pacing over various periods of follow-up. In
      patients with the long QT syndrome in whom medical therapy had failed, pacing at
      relatively fast rates markedly reduced symptoms and almost completely abolished
      fainting spells. Preliminary results suggest that pacing may be beneficial in
      dilated cardiomyopathy and in preventing episodes of paroxysmal atrial
      fibrillation. Further studies are needed to clarify the mechanisms of and to
      improve selection criteria for pacing in these conditions. Our ability to select
      cardiac transplant recipients for permanent pacing and our ability to optimize
      the timing of pacing in these patients have recently improved considerably. The
      role of pacing therapy in patients with neurally mediated (vasovagal) syncope
      remains incompletely understood. Better classification of these patients, made
      according to the sequence of hemodynamic events leading to syncope, is likely to
      clarify the potential benefit of pacing in these patients and improve the
      selection of patients for pacing. CONCLUSION: Few peer-reviewed clinical trials
      have been done, and further studies are needed to confirm the promising effects
      of pacing in patients with these newly recognized and expanding indications for
      pacing.

PMID- 7639446
TI  - Severe osteoporosis in men.
AB  - OBJECTIVE: To evaluate men with severe osteoporosis for pathogenetic factors and
      to review the reported features of primary osteoporosis in men. DESIGN: Case
      series and clinical review. PATIENTS: 47 men consecutively referred to a
      metabolic bone center because of atraumatic (or minimally traumatic) fractures
      (91%) or radiographic osteopenia (9%). MEASUREMENTS: Clinical assessment,
      radiographs, chemical analyses of serum and urine, hormone assays, skeletal
      densitometry, and histomorphometry of iliac crest biopsy specimens. RESULTS: 27
      of the 47 men (57%) had vertebral fractures, and 16 (34%) had appendicular
      fractures. Causal factors identified in 30 men (64%) included glucocorticosteroid
      treatment (8 men); hypogonadism (7 men); excessive alcohol consumption (7 men);
      and anticonvulsant use, osteomalacia, severe hyperthyroidism, or bone marrow
      neoplasia (8 men). Seventeen men (36%) had no medical conditions or known risk
      factors associated with bone disease. Spinal mineral density was well below the
      mean value for healthy young men in 94% of the patients with primary osteoporosis
      tested. Examination of biopsy specimens from 13 of 17 men with primary
      osteoporosis showed reduced trabecular bone volumes, normal bone formation rates,
      and slightly increased resorption surfaces. Fasting hypercalciuria was seen in
      some men (41%). In the primary osteoporosis group, eight men were followed
      serially (range of follow-up, 6 months to 9 years) while they were receiving a
      nonpharmacologic regimen (diet and activity); the mean axial bone mineral density
      of these men increased slightly. CONCLUSIONS: A thorough evaluation for
      identifiable causes of severe osteoporosis in men is warranted because definable
      pathogenetic factors are seen in many cases. A few men with severe osteoporosis
      have primary or idiopathic osteoporosis. Primary osteoporosis in men is probably
      caused by many factors because heterogeneous clinical, laboratory, and histologic
      features were seen in our series and in those of others. Further studies of
      primary osteoporosis are needed to define the course of the disease, to identify
      pathogenetic mechanisms, and to develop therapeutic interventions.

PMID- 7639447
TI  - Drug legalization, harm reduction, and drug policy.
AB  - The current U.S. policy options on drug use are reviewed in the context of the
      history of drug policy in the United States. A restrictive drug policy is a
      deterrent to drug use and helps reduce drug-related costs and societal problems.
      Although legalization or decriminalization of drugs might reduce some of the
      legal consequences of drug use, increased drug use would result in harmful
      consequences.

PMID- 7639448
TI  - Osteoporosis and the primary care physician: time to bone up.

PMID- 7639449
TI  - Perception and regulation of drug use: the rise and fall of the tide.

PMID- 7639450
TI  - Undocumented HIV infection.

PMID- 7639451
TI  - Undocumented HIV Infection.

PMID- 7639452
TI  - Irritable bowel syndrome.

PMID- 7639453
TI  - Host-directed therapy for AIDS.

PMID- 7639454
TI  - Life-threatening bleeding in a patient treated with cefonicid.

PMID- 7639455
TI  - A case of severe withdrawal syndrome due to dextropropoxyphene.

PMID- 7639456
TI  - Nonabandonment: medical ethics.

PMID- 7639457
TI  - Nonabandonment: medical ethics.

PMID- 7639458
TI  - Nonabandonment: medical ethics.

PMID- 7639459
TI  - Nonabandonment: medical ethics.

PMID- 7639460
TI  - Nonabandonment: medical ethics.

PMID- 7639461
TI  - Nonabandonment: medical ethics.

PMID- 7639462
TI  - Nonabandonment: medical ethics.

PMID- 7639463
TI  - Nonabandonment: medical ethics.

PMID- 7639464
TI  - Immigrants and health care.

PMID- 7639465
TI  - Immigrants and health care.

PMID- 7639466
TI  - Cholesteatoma surgery: the individualized technique.
AB  - A retrospective analysis of 433 cholesteatoma cases, surgically treated at the
      Gruppo Otologico, Piacenza, Italy, over a 7-year period, is reported. The purpose
      of this study was to delineate actual indications for individualizing open and
      closed procedures and to compare their results as regards residual or recurrent
      disease and hearing. The total incidences of residual and recurrent cholesteatoma
      in the open cavity procedures were 10% and 2.38%, respectively, while the closed
      procedures showed higher incidences of residual and recurrent cholesteatoma:
      31.22% and 11.16%, respectively. The problem of a persistently discharging cavity
      was encountered in only 1 case of an open procedure, while 2 patients had
      persistent otorrhea among the closed cavity cases. The hearing results, although
      slightly better in the closed procedures, were not significantly different from
      those in the open procedures.

PMID- 7639467
TI  - Laryngeal dysplasia: epidemiology and treatment outcome.
AB  - A retrospective analysis was undertaken of 65 patients with long-term follow-up
      for laryngeal squamous dysplasia. Based on the degree of dysplasia demonstrated
      on initial biopsy, 0 of 6 patients showing hyperkeratosis without dysplasia, 3 of
      26 patients (12%) showing mild dysplasia, 5 of 15 patients (33%) showing moderate
      dysplasia, 4 of 9 patients (44%) showing severe dysplasia, and 1 of 9 patients
      (11%) showing carcinoma in situ eventually progressed to invasive carcinoma. An
      analysis was made of the impact of various treatment modalities in 33 patients
      demonstrating moderate dysplasia, severe dysplasia, or carcinoma in situ.
      Invasive carcinoma developed in 10 of 21 patients (48%) treated endoscopically
      and 0 of 12 patients treated by more aggressive therapy, including external beam
      radiotherapy, partial laryngectomy, or total laryngectomy. Of the patients in the
      endoscopic therapy group who developed invasive carcinoma, all were salvaged
      successfully. The overall rate of laryngeal preservation was 15 of 21 patients
      (71%) in the endoscopic treatment group and 11 of 12 patients (92%) in the
      aggressive treatment group. This difference is not statistically significant. We
      conclude that there is a moderately high rate of progression to invasive
      carcinoma in patients undergoing repeated endoscopic therapy for intraepithelial
      neoplasms of the larynx. However, with close, long-term follow-up, patients
      undergoing endoscopic therapy have an overall outcome similar to that in patients
      treated with partial laryngectomy or radiotherapy prior to developing invasive
      disease.

PMID- 7639468
TI  - Improvement of dysphagia following cricopharyngeal myotomy in a group of elderly
      patients. Histochemical and biochemical assessment of the cricopharyngeal muscle.
AB  - Cricopharyngeal myotomy is not effective in all cases of dysphagia. However, it
      should be the specific treatment in cases of dysphagia caused by a primary
      cricopharyngeal muscle dysfunction. Of a group of 10 patients with swallowing
      disorders in the absence of any defined cause, 7 (mean age, 81.6 years) were
      improved by a myotomy and 3 were not. The cricopharyngeal muscle was studied
      histologically and biochemically and compared to muscle obtained from
      nondysphagic subjects. In the muscle of the 7 improved patients, homogeneous
      histologic abnormalities were demonstrated: connective tissue infiltration,
      inflammatory cell infiltration, and degenerative changes of the muscle fibers.
      Conversely, muscles of the nonimproved patients and of the controls did not
      present the same degree of histologic lesions.

PMID- 7639469
TI  - Microvascular decompression by the retrosigmoid approach for idiopathic
      hemifacial spasm: experience with 300 cases.
AB  - Three hundred patients with idiopathic hemifacial spasm who underwent
      microvascular decompression through the retrosigmoid approach are reported.
      Vascular compression was found in every patient on operation. The results of 1 to
      6 years of follow-up show that 276 patients are free of the symptom, 4 patients
      have markedly diminished spasms and a decreased episode rate, 10 patients have no
      significant relief from the operation, and 9 have had recurrences of the symptom
      since the operation. The cure rate in this group is 92%. Complications were
      sensorineural hearing loss in 13 patients (7 temporary cases, 6 permanent),
      tinnitus in 7 (4 temporary cases, 3 permanent), temporary postoperative facial
      weakness in 16, and postoperative meningitis in 10 (9 cases were controlled with
      antibiotics and 1 patient died).

PMID- 7639470
TI  - Are papillary adenomas endolymphatic sac tumors?
AB  - Papillary adenomas of the temporal bone have been considered as originating from
      the endolymphatic sac. The radiologic, surgical, and pathologic findings in a
      patient suffering from von Hippel-Lindau disease with bilateral papillary
      adenomas of the temporal bone cast some doubt on this site of origin.
      Radiologically, the center of tumor growth was at the top of the jugular bulb.
      Intraoperatively, the tumor was found to have reached the lateral wall of the
      endolymphatic sac, but the lumen was tumor-free. Both ciliated and nonciliated
      tumor cells were found in the resected tumor, resembling the ultrastructure of
      normal epithelial lining in the human mastoid. A strong positive
      immunohistochemical reaction for keratin and negative reactions for vimentin,
      glial fibrillary acidic protein, and S-100 protein in the tumor tissue of this
      patient are typical for middle ear mucosa. Therefore, the described papillary
      adenoma originated from the mucosa of the pneumatic spaces surrounding the
      jugular bulb, and the theory that the endolymphatic sac is the origin of all
      papillary-cystic tumors (adenocarcinomas) should be questioned.

PMID- 7639471
TI  - Effect of otitis media on the vestibular system in children.
AB  - Forty-one children with otitis media (OM) were evaluated by moving platform
      posturography (Equitest, NeuroCom) before and after insertion of tympanostomy
      tubes, and were compared to children with no ear disease (N = 50). Velocity of
      sway increased with increasing difficulty of test conditions (I-VI) for both
      groups of children (p < .001), and children less than 7 years of age had a higher
      velocity than children 7 years old or older (p < .001). Children with OM had a
      higher velocity than normal children (p < .05). For children tested less than 30
      days after insertion of tympanostomy tubes, the velocity for condition VI was
      significantly lower than before insertion (p < .05). Also, that the 6 children
      who had fallen on all trials on condition V or VI were able to stand on these
      trials after insertion of tympanostomy tubes indicates an improvement. These
      findings indicate that episodes of OM may affect balance, leaving children more
      clumsy and accident-prone, and possibly impairing motor development.

PMID- 7639472
TI  - Myringosclerosis caused by increased oxygen concentration in traumatized tympanic
      membranes. Experimental study.
AB  - The purpose of this study was to elucidate possible relationships between the
      oxygen concentration of the middle ear cavity and the development of
      myringosclerosis. Three groups of rats with myringotomized tympanic membranes
      were exposed to different oxygen concentrations of 10%, 15%, and 40%,
      respectively, for 1 week. A fourth group was kept in ambient air. Two other
      groups of rats with myringotomized and intubated tympanic membranes were exposed
      to oxygen concentrations of 10% and 40%, respectively, for the same period of
      time. Otomicroscopically, all hyperoxic animals had more numerous
      myringosclerotic lesions compared with the ambient air group, and also displayed
      a pronounced hyperplasia of the keratinizing epithelium around the perforation
      border. By contrast, the hypoxic animals showed less pronounced myringosclerotic
      lesions or even completely lacked them. It is inferred that an increased oxygen
      concentration in the middle ear cavity will increase the likelihood of
      myringosclerotic deposits. The mechanism involved could be related to the
      formation of oxygen radicals.

PMID- 7639473
TI  - Differential diagnosis of pulsatile neck masses by Doppler color flow imaging.
AB  - A pulsatile neck mass (PNM) requires careful judgment in its evaluation, and it
      is difficult and inaccurate to diagnose a PNM only by physical examination, even
      though a thrill or bruit is present. Doppler colorflow imaging (DCI) was
      performed as an initial evaluation in nine patients with PNMs. Intravenous
      digital subtraction angiography, intra-arterial angiography, X-ray computed
      tomography, and magnetic resonance imaging were performed in selected cases. The
      DCI revealed seven vascular masses (three tortuosities of the common carotid
      artery, two tortuosities of the brachiocephalic artery, one pseudoaneurysm, and
      one traumatic arteriovenous fistula) and two nonvascular masses (one neurofibroma
      and one metastatic lymph node). The clinical diagnoses of all the vascular masses
      were defined by DCI. In nonvascular masses, fine-needle aspiration biopsy could
      be performed relatively safely and accurately by monitoring the feeding artery or
      the common carotid artery by DCI. This method was quite useful for the initial
      evaluation in the differential diagnosis of PNMs.

PMID- 7639474
TI  - Respiratory epithelial adenomatoid hamartomas of the sinonasal tract and
      nasopharynx: a clinicopathologic study of 31 cases.
AB  - We report the clinicopathologic features of 31 cases of respiratory epithelial
      adenomatoid hamartomas occurring in the nasal cavity, paranasal sinuses, and
      nasopharynx. The patients included 27 men and 4 women ranging in age from 27 to
      81 years (median, 58 years). Symptoms included nasal obstruction, nasal
      stuffiness, deviated septum, epistaxis, and chronic (recurrent) rhinosinusitis.
      The symptoms occurred over various time periods from as short as a few months to
      up to 8 years in duration. Physical examination identified the presence of a
      polypoid mass lesion(s), most often identified in one or both nasal cavities (n =
      22). Within the nasal cavity the most common site of occurrence was the nasal
      septum, particularly along its posterior aspect. Other areas within the nasal
      cavity were also involved, as were the ethmoid sinus, frontal sinus, and
      nasopharynx. The gross appearance of the mass lesions suggested a diagnosis of an
      inflammatory polyp, but because of subtle differences, including frequent
      occurrence along the nasal septum and a more indurated quality, these polyps were
      considered unusual for the typical inflammatory polyps. Histologically, these
      lesions were characterized by a prominent glandular proliferation lined by
      ciliated respiratory epithelium originating from the surface epithelium. The
      differential diagnosis of these adenomatoid hamartomas includes schneiderian
      papillomas of the inverted type and adenocarcinomas. Diagnostic
      misinterpretations may result in untoward surgical intervention. Limited but
      complete surgical resection was the treatment of choice, following which there
      were no instances of recurrent disease.

PMID- 7639475
TI  - Quantitative bacteriology of tonsils removed from children with tonsillitis
      hypertrophy and recurrent tonsillitis with and without hypertrophy.
AB  - The aerobic and anaerobic bacterial species and their numbers were studied in
      tonsillar specimens from children who had undergone elective tonsillectomy: 6
      patients with recurrent tonsillitis (RT), 9 with recurrent tonsillitis with
      hypertrophy (RTH), and 8 with obstructive tonsillar hypertrophy (OTH). Mixed
      flora were present in all tonsils, yielding an average of 6.7 isolates (5.6
      aerobic or facultative and 1.1 anaerobic bacteria). The highest recovery rate of
      organisms per tonsil was in patients with OTH (7.7 per tonsil), compared to 6.3
      per tonsil in RT and 5.9 per tonsil in RTH. The predominant aerobic and
      facultative organisms were Haemophilus influenzae (22 isolates), Neisseria sp
      (16), Staphylococcus aureus (14), and Eikenella corrodens (14), and the
      predominant anaerobic bacteria were Fusobacterium sp (8), Bacteroides sp (7), and
      Prevotella melaninogenica (5). The number of bacteria per gram of tonsillar
      tissue varied between 10(4) and 10(8). A higher concentration of S aureus and H
      influenzae was found in hypertrophic tonsils (RTH and OTH) as compared to RT.
      These findings suggest the presence of an increased bacterial load and supports
      an etiologic role for H influenzae and S aureus in hypertrophic tonsils with and
      without inflammation (RTH and OTH). Further studies to elucidate the effect of
      selective antimicrobial therapy directed at these organisms may offer an
      alternative management of hypertrophic tonsils.

PMID- 7639476
TI  - Pharyngeal and pharyngolaryngeal bands: report of an unusual combination of
      congenital anomalies.
AB  - Multiple abnormal pharyngeal and pharyngolaryngeal bands were present in a child
      presenting with diffuse interstitial pulmonary fibrosis. The soft palate was
      fused to the posterior pharyngeal wall. Instead of there being facial pillars, a
      muscular band on either side extended from the base of the tongue to the lateral
      pharyngeal walls. There was neither tonsil nor adenoid tissue present. The
      epiglottis was tethered to the posterior pharyngeal wall by bands from its
      lateral aspects. The right arytenoid mound was tethered to the posterior wall of
      the hypopharynx. It is postulated that these arose from a failure of development
      of the second branchial pouch.

PMID- 7639477
TI  - Beta-Amyloid peptide and amyloid precursor proteins in olfactory mucosa of
      patients with Alzheimer's disease, Parkinson's disease, and Down syndrome.
AB  - Dystrophic neurites are present in olfactory epithelium (OE) of patients with
      Alzheimer's disease (AD), Parkinson's disease (PD), and Down syndrome (DS) and
      occasionally in normal individuals. Cultured olfactory neuroblasts from AD
      patients generate carboxy terminal amyloid precursor protein (APP) fragments that
      contain beta-amyloid (A beta), but it is not known if deposits of A beta and/or
      APP fragments occur in the OE of individuals with or without AD, PD, or DS. To
      determine if A beta accumulates in the OE in situ, we probed postmortem samples
      of olfactory mucosa from patients with AD, PD, and AD (PD/AD), and DS and AD
      (DS/AD), as well as from controls, using polyclonal and monoclonal antibodies to
      A beta and flanking sequences in APPs. Samples of OE also were examined by
      thioflavin-S and electron microscopy. Labeling of A beta was observed in 10 of 12
      AD cases, 2 of 3 PD/AD cases, 3 of 4 DS/AD cases, 3 of 10 adult controls, and 4
      of 6 fetal cases. The A beta staining was seen in the basal third of the OE, in
      axons projecting through the lamina propria, and in metaplastic respiratory
      epithelium within the OE. Antibodies to other APP domains stained the OE of
      patients and controls. Thioflavin-S staining was present in the basal third of
      the OE of 8 of 9 AD patients and several PD/AD and DS/AD patients, but only in
      rare cells of 3 controls. Electron microscopy did not reveal amyloid fibrils in
      the OE.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7639478
TI  - Cervical lymphangioma with simultaneous skull base invasion and soft tissue
      regression.

PMID- 7639479
TI  - Intranasal astrocytoma.

PMID- 7639480
TI  - Role of mini- and microplate fixation in fractures of the midface and mandible.
AB  - Le Fort defined the classic weak points of facial fractures. Fractures of the
      midface and mandible are believed to require management with standard rigid
      fixation. Recent work has allowed mini- and microplating of multiple fracture
      fragments into more manageable larger segments for reduction and subsequent
      plating with rigid fixation to peripheral buttresses. The technique and
      indications for use are outlined.

PMID- 7639481
TI  - Periorbital soft-tissue and socket reconstruction.
AB  - Deformities of the periorbital soft tissue and socket after trauma or infection
      may involve the bony framework, orbital contents, and periorbital soft tissues,
      requiring careful evaluation. Soft-tissue reconstruction necessitates the
      appreciation of a three-dimensional defect.  Structural reconstruction in
      conjunction with prosthetic replacement of the globe requires careful planning.
      Three cases illustrating problems and results after reconstructions are
      presented.

PMID- 7639482
TI  - Chest wall reconstruction for radionecrosis after breast carcinoma therapy.
AB  - This study aimed at evaluating various reconstructive procedures for chest wall
      radionecrosis after breast carcinoma therapy. Four different techniques were
      performed between 1973 and 1992 in 120 patients: latissimus dorsi
      musculocutaneous flap (LDF; n = 81); transposed omentum and split-thickness skin
      graft (TGO; n = 20); fasciocutaneous flap (FCF; n = 10), and transverse rectus
      abdominis musculocutaneous flap (TRAM; n = 9). Initial dose of irradiation ranged
      from 60 to 110 Gy. The average interval between initial treatment and
      reconstruction was 11 years. Local recurrence was suspected in 26 patients and
      was histologically proven after removal in 36 (30%). Surgical procedure results
      were analyzed by mean hospital stay (8 days for LDF vs. 52 days for TGO), early
      (13% LDF vs. 60% TGO) and late (7% LDF vs. 35% FCF) complications, second surgery
      (15% LDF vs. 53% FCF), and functional and cosmetic outcomes. In our experience,
      the LDF was the first-line flap. The TRAM was used to cover very large defects
      and when breast reconstruction was needed. When these flaps were impossible or
      dangerous, we performed a TGO. These three procedures have replaced FCF
      indications.

PMID- 7639483
TI  - Transposition of the greater omentum for recalcitrant median sternotomy wound
      infections.
AB  - During a 3-year period, 25 patients underwent transposition of the greater
      omentum, either alone or in combination with muscle flaps, for treatment of
      recalcitrant median sternotomy wound infections. Most patients underwent radical
      sternectomy for deep and extensive sternal wounds; the others had significant
      defects involving the lower third of the sternum. The most common combination of
      flaps was omentum and bilateral pectoralis major musculocutaneous flaps (14
      patients). Delay to reconstruction after the recognition of median sternotomy
      infection ranged from 2 to 36 days (average, 13.9 days) except for one patient
      treated outside by the "open method" for 18 months. Definitive closure was
      performed after an average of 1.8 debridements (range, 1-4). Hospitalization
      averaged 28.5 days (range, 13-42 days) in 16 of the 19 surviving patients. The
      majority of these patients had far more extensive sternal defects than those
      usually treated by muscle flaps alone. Healing was ultimately achieved in 95% of
      infected sternotomy wounds. Seventy-four percent of patients healed their sternal
      wounds uneventfully without subsequent problems. Flap site complications in the
      remaining patients included recurrent chondritis (16%) and partial (4%) or
      complete (4%) flap loss. Donor-site complications included abdominal wall
      herniation (21%), hematoma (8%), and seroma (4%). There were no problems with
      chest wall instability or intra-abdominal morbidity. Six patients (24%) succumbed
      to multisystem failure unrelated to sternal infection. We present our experience-
      including indications, technique, and outcome--with transposition of the greater
      omentum for recalcitrant median sternotomy wound infections.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7639484
TI  - Tissue expansion-assisted prefabrication of the forehead flap for nasal
      reconstruction.
AB  - A new technique for nasal reconstruction is described. This method--expansion
      assisted flap prefabrication--is essentially a simultaneous application of
      pretransfer grafting and tissue-expansion procedures for creating custom-made
      forehead flaps to meet varying requirements of nasal reconstruction. We have
      applied this new technique on seven patients, with full-thickness nasal defects
      during a 3-year period. Results from these patients are presented with a review
      of different use of flap prefabrication principles in nasal reconstruction.

PMID- 7639485
TI  - Reconstruction of the sole and heel and infancy in childhood followed up for more
      than 10 years.
AB  - We evaluated 10 patients in which the initial reconstruction of the weight
      bearing area of the sole and heel was performed in infancy or childhood and which
      had been followed up more than 10 years. In the initial operations, a cross-leg
      flap was used in 5, full-thickness skin graft in 5, and split-thickness skin
      graft in 1 (in 1 patient, both a cross-leg flap and a full-thickness skin flap
      was used). Secondary reconstruction was performed using skin graft from non
      weight-bearing areas in 6 patients and a cross-leg flap in 1 patient. In infancy
      and childhood, temporary closure of a wound by skin graft from the inguinal area
      or a cross-leg flap was attempted. Initial reconstruction using the non-weight
      bearing area must be performed carefully in infancy and childhood.

PMID- 7639486
TI  - Dry, moist, and wet skin wound repair.
AB  - Effects of wet (saline in a vinyl chamber), moist (hydrocolloid dressing), and
      dry (sterile gauze dressing) environments on wound repair were studied in a
      porcine partial-thickness wound model. Chambers were exchanged and refilled daily
      with normal saline containing penicillin G (100 U/ml) and streptomycin (100
      micrograms/ml). Hydrocolloid and gauze dressings were kept in place until biopsy
      of the wound site. Wounds in wet, moist, and dry environments were completely
      epithelialized on days 6, 7, and 8, respectively. Thickness of the epidermis in
      wet, moist, and dry wounds was 204 +/- 23, 141 +/- 12, and 129 +/- 18 (mean +/-
      SEM), respectively. Moist wounds had more subepidermal inflammatory cells than
      wet wounds. In comparison to dry wounds, the moist or the wet healing environment
      resulted in less necrosis and faster and better quality of healing in the
      formation of the newly regenerated epidermis.

PMID- 7639487
TI  - Free temporoparietal fascia flap in reconstruction of the lower extremity.
AB  - Twenty-one patients with open wounds of the non-weight-bearing foot or the ankle
      underwent coverage with a free temporoparietal fascia flap and split-thickness
      skin graft. Our indications for this thin, well-vascularized flap included
      osteomyelitis and exposed tendon, bone, or fixation hardware. The pliability of
      the flap allowed superior restoration of natural anatomical contours. Only one
      flap was completely lost (95.2% overall success). There were four cases (20%) of
      partial flap loss, none of which required flap revision or a new flap. Four
      patients (19%) experienced transient donor-site alopecia, and one patient
      suffered transient palsy of the temporal branch of the facial nerve. One patient
      (4.7%) had an area of persistent scar alopecia in the temporal scalp after a
      donor-site hematoma that required revision under local anesthesia. Follow-up was
      available on 95% of the patients and averaged 20 months (range, 1-54 months). All
      patients resumed weight-bearing ambulation within 1 month from operation using
      unmodified footwear. The free TPF flap is a reliable coverage option, with long
      term durability and minimal donor-site morbidity, for relatively superficial
      wounds of the distal lower extremity.

PMID- 7639488
TI  - Use of recovery-enhanced thermography to localize cutaneous perforators.
AB  - Recovery-enhanced thermography implies the scanning, after cooling, of the skin
      surface with ice water for several seconds. Using this method, cutaneous
      perforators were clearly identified in constant distributions on the trunks of 12
      healthy volunteers. Clinically, preoperative recovery-enhanced thermography is
      useful for the design of perforator-based flaps. We describe this method in
      detail and demonstrate its reliability with successful clinical cases.

PMID- 7639489
TI  - Midface distraction advancement in the canine without osteotomies.
AB  - Midface hypoplasia, often associated with exorbitism and malocclusion, has been
      traditionally corrected by using Le Fort advancement osteotomies through wide
      surgical exposure. These procedures suffer the disadvantages of hemorrhage,
      unpredictable bone graft resorption, the need for retained hardware, and bone
      graft donor-site morbidity. We present an investigation of midface distraction in
      the canine without osteotomies. Five canines were the subjects of this study and
      were divided into two groups. At the time of placement of the lengthening
      devices, Group 1 animals were 10 weeks of age and Group 2 animals were 5 years of
      age. Under general anesthesia, four modified Hoffman bone distractors were
      mounted on 2-mm half pins placed individually across the nasofrontal and the
      zygomaticotemporal sutures on each side of the craniofacial skeleton. Distraction
      of all devices was begun on postoperative day 1 at the rate of 0.5 mm/day for 4
      days and then 1.0 mm/day for 28 days, after which interval the devices were
      removed. The dogs were serially monitored and examined for 3 months. One dog in
      the first group served as a sham control. The results were assessed by
      standardized cephalograms, and craniofacial computed tomographic scans with three
      dimensional reconstruction performed before device placement as well as after
      removal of the device. In one Group 1 animal, computed tomographic scanning was
      performed every 2 to 4 weeks for 3 months. Gross examination of the Group 1
      animals demonstrated the development of enophthalmos, dolichocephaly, and a class
      II malocclusion-overbite.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7639490
TI  - Clinical applications of venous flaps.
AB  - Reconstruction involving seven venous flaps on six patients was performed. One
      saphenous venous flap demonstrated partial dermal necrosis; the remaining six
      survived completely. The largest flap to survive was 5 x 15 cm. Three technical
      requirements are emphasized; (1) a healthy recipient bed, (2) a donor site with a
      luxuriant venous network and a flow-through vein, and (3) stable fixation of the
      flap to its bed.

PMID- 7639491
TI  - Pollicization of the mutilated hand by transposition of middle and ring finger
      remnants.
AB  - Traumatic injuries to the thumb are frequently associated with mutilation of one
      or more of the remaining digits. The most common digital injuries associated with
      thumb loss are partial or complete amputation of the index finger or index and
      long fingers. Occasionally, satisfactory index finger function will be preserved
      with damage or amputation of the middle or ring fingers, making them the best
      candidates for transposition. Although pollicization of the index finger has
      received considerable attention in the literature, pollicization of injured
      middle and ring finger remnants has not. Transposition of these comparatively
      useless digital stumps, which may be sacrificed without significant functional
      deficit to the rest of the hand, may be advantageously performed to create a well
      functioning thumb. This procedure facilitates the conversion of a useless,
      mutilated hand into a well-functioning one in a single operation. We present our
      experience with pollicization of middle and ring finger remnants in four patients
      including indications, technique, and functional outcome.

PMID- 7639492
TI  - The characteristics of cultured mucosal cell sheet as a material for grafting;
      comparison with cultured epidermal cell sheet.
AB  - The characteristics of cultured mucosal cells from the oral mucosa were
      investigated and compared with those of cultured epidermal cells. Total cell
      counts showed that mucosal cells possessed greater proliferating ability than
      epidermal cells. The results of 3(4,5-dimethyle-thiazoyl-2-yl)2,5
      diphenyltetrazolium bromide assay confirmed this observation and also suggested
      that the mucosal cells maintained biological activity longer than epidermal
      cells. The most important morphological characteristics of mucosal cells in
      culture were their low grade of differentiation. Interestingly, the epidermal
      cells showed enucleation and keratinization progressively during culture, whereas
      the mucosal cells showed no obvious enucleation when examined by light
      microscopy. Transmission electron microscopy showed a smaller number of
      desmosomes in cultured mucosal cells than epidermal cells. The results of this
      study reveal cultured mucosal cell sheets to be a possible material for grafting
      in addition to cultured epidermal cell sheets.

PMID- 7639493
TI  - Effect of skin-graft harvesting on hair growth; implications for the study of
      alopecia.
AB  - An experiment using guinea pigs was performed to demonstrate the feasibility of
      repeated skin-graft harvesting as a model system in the study of diffuse
      alopecia. In response to four split-thickness skin harvests from the same site at
      2-week intervals, the number of hairs observed and follicular area doubled,
      implying a transition of hair follicles from vellus to terminal, compared with
      ungrafted control skin from the alternate side of the same animals. The guinea
      pig may serve as a future model for the study of diffuse alopecia because its
      hair growth patterns are similar to those observed in humans.

PMID- 7639494
TI  - Successful elimination of traumatic tattoos by the Q-switched alexandrite (755
      nm) laser.
AB  - Traumatic tattoos are very difficult to eradicate because of the resultant deep
      penetration of foreign body particles. Previous treatments, such as surgical
      excision and dermabrasion, commonly resulted in incomplete removal or significant
      scarring or both. Three patients with traumatic tattoos were treated with the Q
      switched alexandrite laser (755 nm), with complete lesional resolution observed
      after one to four treatments. No adverse sequelae, such as scarring or pigmentary
      alteration, were noted in the laser-irradiated skin.

PMID- 7639495
TI  - Facial nerve palsy after mandibular fracture.
AB  - A 19-year-old man sustained a right parasymphyseal fracture and bilateral
      condylar neck fractures in a motor vehicle accident. The parasymphyseal fracture
      was treated by open reduction and internal fixation, and the subcondylar
      fractures were treated with closed reduction and maxillomandibular fixation.
      Three days postoperatively, a near-complete left facial nerve palsy developed.
      Facial nerve recovery was not full. The literature is reviewed, and possible
      mechanisms of this rare and devastating complication are discussed.

PMID- 7639496
TI  - Bilateral snapping triceps tendon after bilateral ulnar nerve transposition for
      ulnar nerve subluxation.
AB  - Reports of subluxation of the medial head of the triceps tendon over the medial
      epicondyle are rare. This may be associated with symptomatic ulnar nerve
      compression at the elbow. We report a case of bilateral snapping triceps tendon
      after bilateral ulnar nerve release at the elbow with anterior submuscular
      transposition. Careful inspection of the triceps tendon in flexion and extension
      at the time of the ulnar nerve submuscular transposition may prevent this
      potential complication.

PMID- 7639497
TI  - Earliest attempt at free skin grafting.

PMID- 7639498
TI  - A new method of skin-graft stabilization: the Reston technique.
AB  - We describe a new staple-on dressing technique for skin-graft stabilization,
      using gas-sterilized polyurethane foam as bolster material. The method has all
      the attributes of a satisfactory skin-graft dressing: compression to prevent
      hematoma and seroma, resistance to shear forces, splinting properties, and
      protection from the outside environment. Although we have not completed a
      randomized, prospective study, skin-graft "take" appears to be excellent in most
      cases. The technique is cost effective, and application requires a fraction of
      the time required for a traditional bolster dressing.

PMID- 7639499
TI  - All I really need to know about cooking I learned in the operating room.

PMID- 7639500
TI  - Re: Reduction mammaplasty for gigantomastia using inferiorly based pedicle and
      free nipple transplantation.

PMID- 7639501
TI  - Re: Composite chondrocutaneous graft.

PMID- 7639502
TI  - Re: Risk of dissemination of cancer to flap donor sites during immediate
      reconstructive surgery.

PMID- 7639503
TI  - [Transient cerebral ischemic complications. The neurologist's point of view].
AB  - Transient ischaemic attacks (TIA) are defined by the focal and sudden loss of a
      cerebral function or the vision of one eye, resolving without sequelae within 24
      hours and related to a vascular cause, thromboembolic much more frequently than
      haemodynamic. TIA represent between 9% and 25% of all cerebrovascular accident
      (CVA) with a variable global incidence from one study to another, between 0.2 and
      3.3/1,000/year. The natural history of TIA is characterized by an excess
      mortality and an increased risk of cerebral infarction and myocardial infarction.
      It is therefore essential to recognize these events in order to prescribe
      effective preventive treatment. The clinical picture is characterized by a
      usually brief focal deficit (2 to 30 min, on average) and a normal clinical
      examination. The diagnosis is therefore exclusively based on the clinical
      interview. Complementary investigations have a dual objective: 1) to eliminate
      other diseases likely to cause transient neurological manifestations, and 2) to
      detect the mechanism and cause of cerebral ischaemia; the commonest causes are
      atheromatous stenosis and emboligenic heart disease. In addition to the routine
      laboratory examinations, basic complementary investigations consist of cerebral
      CT scan, cervical ultrasound and echocardiography. Conventional angiography is
      performed less and less frequently due to the progress in ultrasound and vascular
      imaging (helicoidal CT scan and magnetic resonance angiography). The treatment of
      TIA is designed to prevent cerebral and myocardial infarction, and to decrease
      the cardiovascular mortality [2]. In the short-term, it is essentially based on
      heparin, while waiting for the results of the aetiological assessment.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7639504
TI  - [Current respective role of surgery and permanent endocavitary stimulation in the
      treatment of hypertrophic cardiomyopathies].
AB  - Surgery and cardiac pacing are the two main non-drug treatments for hypertrophic
      cardiomyopathy. Various surgical techniques have been proposed over the last 35
      years: myotomy, myotomy-septal myomectomy, isolated mitral valve replacement,
      heart transplantation. Patients eligible for surgery are those with severe
      symptoms (NYHA stage III or IV) and refractory or no longer responding to drug
      treatment. The choice between the various techniques is based on morphological
      and haemodynamic criteria (significant subaortic gradient associated with
      increased septal thickness, severe and/or organic mitral regurgitation, either
      isolated or associated with obstruction, or less severe or heterogeneous septal
      thickness [< 18 mm]) or therapeutic criteria (failure of primary myomectomy,
      depletion of all surgical possibilities). Analysis of the results of surgery is
      complicated by the variety of techniques performed and the experience of the
      various teams. The operative mortality was markedly decreased (between 2 and 11%
      at the present time); the complications of myomectomy (ventricular septal defect,
      disturbances of conduction requiring continuous pacing) are still frequent.
      Intraoperative transoesophageal ultrasonography could help to further decrease
      the operative risk. Surgery improves functional symptoms and exercise tolerance.
      This beneficial effect appears to be more marked, more frequent and more lasting
      than that of medical treatment. Surgical treatment does not ensure permanent
      cure, as the symptoms related to pathophysiological abnormalities other than
      intraventricular obstruction (abnormalities of diastolic filling, myocardial
      ischaemia, arrhythmias) may develop subsequently. No controlled trial has
      demonstrated a favourable effect on survival. Continuous pacing, introduced more
      recently, can now be considered to be a therapeutic method in its own
      right.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7639505
TI  - [Comparison of the efficacy of enalapril + hydrochlorothiazide and captopril +
      hydrochlorothiazide combinations in mild-to-moderate arterial hypertension by
      ambulatory measurement of blood pressure].
AB  - This two-centre trial compared the efficacy of combinations of enalapril +
      hydrochlorothiazide (E + H) and captopril + hydrochlorothiazide (C + H) on mild
      to-moderate hypertension, after a two-week placebo period, in 26 patients with
      mild-to-moderate HT (DBP between 95 and 114 mmHg) not controlled by previous
      treatment, randomized under double-blind conditions into two groups for two 4
      week crossover treatment periods separated by a 4-week wash-out period. One group
      received E + H (20 mg/12.5 mg) followed by C + H (50 mg/25 mg) and the other
      group received C + H (50/25) followed E + H (20/12.5), once a day. The efficacy
      of the two treatments was evaluated by 24-hour ambulatory blood pressure
      monitoring (ABPM) at the start of the study and after each treatment period.
      Plasma renin activity, aldosterone and angiotensin converting enzyme were assayed
      under the same conditions. Analysis was based on 26 cases, as none of the
      patients were withdrawn from the trial. No difference was observed between the
      two groups in terms of the main biometric and laboratory characteristics. Blood
      pressure evaluated by ABPM and intermittently was not significantly different
      between the two groups at the time of inclusion in the study. On intermittent Bp
      determinations, E + H and C + H decreased diastolic and systolic blood pressure,
      with no significant difference between the two treatments. On ABPM, the two
      treatments significantly decreased mean systolic, diastolic and mean blood
      pressure during the diurnal, nocturnal and circadian periods.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7639506
TI  - Inactivation and cleavage of liver 6-P-gluconate dehydrogenase during irradiation
      in the presence of vanadate.
AB  - Lamb liver phosphogluconate dehydrogenase is inactivated and selectively cleaved
      during irradiation in the presence of vanadate. Under our experimental
      conditions, the correlation between the species of vanadate in solution and rates
      of enzyme inactivation and cleavage indicates tetravanadate as the most likely
      photosensitizing agent, in agreement with previous data on other proteins. The
      enzyme is inactivated more rapidly at acidic pH and is partially protected by the
      coenzyme NADP, but not by the substrate phosphogluconate. Complete inactivation
      is obtained when only half of the protein is cleaved into smaller peptides.
      Differences in the pattern of the peptides produced are observed when irradiation
      is carried out in phosphate rather than in Hepes buffer: in the former instance
      cleavage results into formation of a main peptide of 47 kDa, while in latter case
      two additional peptides of 31 and 25 kDa are produced.

PMID- 7639507
TI  - Reactivity of the H(+)-ATPase from Kluyveromyces lactis to sulfhydryl reagents.
AB  - N-Ethylmaleimide (NEM) inhibited the H(+)-ATPase (EC 3.6.1.35) from Kluyveromyces
      lactis with a second-rate constant of 200 M-1 min-1. H(+)-ATPase was partially
      protected by Mg-ADP. Low concentrations of Mg protected ATPase from the effects
      of NEM, while high Mg sensitized ATPase to NEM. The reaction of 14C-NEM with the
      native enzyme modified three cysteine residues/monomer, two of which were
      involved in 80% of the inactivation of the enzyme. In the presence of Mg-ADP, NEM
      binding to the first residue had only a slight effect on the activity (10-20%
      inhibition). After further incubation, the modification of a second cysteine
      residue (probably cys-221) inactivated the ATPase. Methyl methanethiosulfonate
      did not inhibit the H(+)-ATPase but resulted in a NEM-resistant H(+)-ATPase.
      There seems to be at least one cys (probably cys-532) at, or near, the nucleotide
      binding site of the H(+)-ATPase, which does not appear to be essential for
      activity. Modification of a second cys residue (cys-221) also resulted in
      inactivation by NEM; this residue was not protected by ADP and thus probably is
      not at the ATP binding site.

PMID- 7639508
TI  - Superoxide anion generation by human peripheral blood mononuclear cells in
      response to prothymosin alpha.
AB  - The ability of human peripheral blood mononuclear cells to respond to highly
      purified prothymosin alpha by generating superoxide anion was investigated. The
      generation of superoxide anion was detected by measuring the superoxide dismutase
      inhibitable reduction of oxidized cytochrome C. Prothymosin alpha was shown to
      stimulate weakly these cells. The dose-response curve displayed a biphasic bell
      shaped superoxide generation profile with two specific concentration optima for
      each individual blood donor, but with variations in optimal concentrations
      between the donors. By using a counter current centrifugation (elutriation)
      system, the mononuclear cell population was separated into several fractions
      according to their volume and density. Selective stimulation of these fractions
      with prothymosin alpha revealed that different cell populations were responsible
      for the generation of superoxide at higher and lower concentrations of stimulant,
      respectively. The response to the stimulus was immediate and lasted for a time
      period of about 4 to 8 min during which approximately 0.7 nmol O2- per min/10(6)
      cells were generated. The superoxide generation was cell-number-dependent with an
      optimum at 1 x 10(6) cells and lower rates for both smaller and larger cell
      numbers. Staurosporine, a potent inhibitor of protein kinase C, at concentrations
      sufficient to inhibit totally PMA-induced O2- generation, failed to affect the
      response of the cells to prothymosin alpha, while chelation of the extracellular
      Ca2+ abolished the lower but not the higher peak of O2- generation. Finally,
      simultaneous addition of prothymosin alpha and PMA resulted in a approximately
      40% decrease of the O2- generation induced by PMA alone. A putative role as cell
      injury indicator is proposed for prothymosin alpha.

PMID- 7639509
TI  - Diurnal rhythms of rat liver serine dehydratase, D-site binding protein, and 3
      hydroxy-3-methylglutaryl coenzyme A reductase mRNA levels are altered by
      destruction of the suprachiasmatic nucleus of the hypothalamus.
AB  - It is generally accepted that a clock generating biological rhythms exists in the
      suprachiasmatic nuclei (SCN) of the hypothalamus in rodents. We have examined if
      diurnal variations of rat liver serine dehydratase (SDH), D-site binding protein
      (DBP), and 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMGR) mRNA levels,
      each of which exhibits low values during the daytime (06:00-18:00) and high
      values during the dark period, are controlled by the SCN. The SCN were destructed
      electrolytically, and, 2 weeks later, rats were sacrificed at 06:00, 12:00,
      18:00, and 24:00. Completeness of SCN lesions was assessed by the alteration of
      spontaneous locomotor activity and histological examination of the brains. The
      SDH and DBP mRNA levels in SCN-lesioned rats were very low at 06:00 and almost
      eliminated at 18:00, whereas the HMGR mRNA level at 06:00 was low at 06:00 and
      slightly increased at 18:00 compared to the control values. When determined at
      12:00 and 24:00, the SDH, DBP, and HMGR mRNA levels in sham-operated rats were
      higher at 24:00 than at 12:00, whereas those in SCN-lesioned rats were higher at
      12:00 than at 24:00. The hepatic beta-actin and glycine N-methyltransferase mRNA
      levels showed no significant diurnal variation and were not affected by SCN
      lesions. These results indicate that the SCN also play a pivotal role in
      determining rhythmic gene expression in liver.

PMID- 7639510
TI  - Identification of the residues responsible for the alkaline inhibition of the
      activity of Cu,Zn superoxide dismutase: a study of native and chemically modified
      enzymes.
AB  - The pH dependence of the activity of Cu,Zn superoxide dismutases from bovine
      erythrocytes and shark liver was studied by pulse radiolysis in both the native
      enzymes and those chemically modified at lysine side chains. The study was aimed
      at identifying the residues responsible for the activity decrease at pH > 9,
      observed in all native Cu,Zn superoxide dismutases, and is based on the Lys-->Arg
      substitution present in the shark protein at position 134, which has been
      established to be critical for the catalytic efficiency of the enzyme. Both
      native enzymes display a pH dependence that can be deconvoluted by three
      deprotonation equilibria, at pH 9-9.5 (pK1), at pH 10.2 (pK2), and at pH 11.5
      (pK3). pK1 is lacking in both the modified enzymes and thus can be assigned to
      activity-linked lysine residues. pK2 is clearly dominated by Arg134 in the
      modified shark enzyme and can be assigned to surface arginine residues. pK3 is
      shared by all four enzyme forms and is likely to be due to the invariant Arg141.

PMID- 7639511
TI  - Dual effect of lipid peroxidation on the membrane order of retinal cells in
      culture.
AB  - The effect of lipid peroxidation, induced by ascorbic acid and ferrous sulfate
      (Fe2+) at pH 7.4 or pH 6.5, on the membrane order of retinal cells in culture was
      examined. Membrane order was measured by fluorescence anisotropy using 1-[4
      (trimethylammonium)-phenyl]-6-phenylhexa-1,3,5-triene as a fluorescent probe.
      Alterations of cellular membrane order were correlated with the susceptibility to
      peroxidation and viability of these cells. At pH 7.4, 1.5 mM ascorbate/7.5 microM
      Fe2+ induced a low production of thiobarbituric acid-reactive substances (3.47 +/
      0.26 nmol TBARS/mg protein), while 5 mM ascorbate/100 microM Fe2+ significantly
      increased TBARS production to 11.17 +/- 1.43 nmol/mg protein. At pH 6.5, in the
      presence of 5 mM ascorbate/100 microM Fe2+, cellular oxidation was mostly
      increased following 15 min incubation (19.33 +/- 1.66 nmol TBARS/mg protein) and
      decreased thereafter as a result of a prolonged exposure to the oxidizing agents
      to levels of 11.02 +/- 0.66 nmol TBARS/mg protein, after 180 min peroxidation.
      The membrane order of control retinal cells treated at pH 6.5 was not changed
      compared to controls at pH 7.4. Moreover, the membrane order of retinal cells
      peroxidized at pH 7.4 was not significantly different compared to controls, in
      the absence of ascorbate/Fe2+. However, significant time-dependent alterations
      were found in the membrane order of cells peroxidized with 5 mM ascorbate/100
      microM Fe2+, at pH 6.5: cellular membrane order decreased after 15 min
      peroxidation, while longer peroxidative incubation periods, from 60 and up to 180
      min, induced an increase in the membrane order. The dual effect of lipid
      peroxidation, under moderately acidic conditions (pH 6.5), on the membrane order
      of retinal cells was shown to be prevented upon cellular pretreatment with
      vitamin E, supplemented to the culture medium. Moreover, vitamin E pretreatment
      increased the viability of control retinal cells and reduced the production of
      TBARS after 15 min peroxidation with 5 mM ascorbate/100 microM Fe2+, at pH 6.5.
      Vitamin E was also shown to reduce conjugated dienes formation after 15 or 60 min
      peroxidation at pH 6.5.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7639513
TI  - A thermolabile triosephosphate isomerase from the psychrophile Vibrio sp. strain
      ANT-300.
AB  - We report the isolation of a gene encoding triosephosphate isomerase (TIM; EC
      5.3.1.1) from Vibrio sp. strain ANT-300, a psychrophilic marine eubacterium that
      grows optimally at 7 degrees C. The deduced primary sequence of this isomerase is
      50% identical to Escherichia coli TIM and 37% identical to the isomerase of the
      psychrotroph Moraxella sp. TA137. Transformation with this gene allowed growth of
      a TIM-deficient E. coli strain on selective media, but only at temperatures below
      30 degrees C. The temperature dependence of this complementation is likely to
      result from an intrinsic thermolability of the isomerase. Indeed, the TIM
      activity present in ANT-300 lysates is markedly heat-sensitive, with a half-life
      of inactivation of 520 s at 25 degrees C.

PMID- 7639512
TI  - Expression of cytochrome P450 genes of the CYP4 family in midgut and fat body of
      the tobacco hornworm, Manduca sexta.
AB  - Two conserved regions in the alignment of cytochrome P450 family 4 (CYP4)
      proteins served as guide to the synthesis of degenerate oligonucleotide primers.
      The primers were used in PCR from a midgut cDNA library and RT-PCR from fat body
      mRNA, both from last instar larvae of the tobacco hornworm, Manduca sexta. The
      PCR products of 443-449 bp were cloned and sequenced. Nine P450 clones
      representing four new genes were obtained from the midgut. Fifteen P450 clones
      representing three new genes were obtained from the fat body. Two genes were
      expressed in both tissues. A number of putative allelic variants were also
      observed for three of the P450 genes. The resulting sequences of 130-132 amino
      acids were aligned to generate a parsimony analysis of CYP4 P450 proteins. Two
      new subfamilies of CYP4 were designated from M. sexta by these procedures, CYP4L
      and CYP4M. The sequence of a full-length cDNA clone for CYP4M2 (41.2% identity to
      CYP4C1) confirmed that the PCR products obtained by this method were P450s
      belonging to the CYP4 family. The developmental expression of the CYP4 genes
      appeared to be coordinately regulated in both fat body and midgut. In the fat
      body, CYP4 mRNA levels declined after the first day of the final larval instar,
      peaked during the wandering stage, and fell again until the prepupal molt. Midgut
      CYP4 mRNA levels were higher during the active feeding, midwandering, prepupal,
      and pupal stages. Addition of 2-tridecanone or 2-undecanone to the diet induced
      several P450s in the midgut and in the fat body. Phenobarbital induced CYP4M1 in
      the fat body and dietary clofibrate induced the mRNA levels of CYP4M1 and CYP4M3
      in the midgut. The results indicate that at least four CYP4 genes are expressed
      in single tissues of a Lepidopteran insect. Several of these P450 may be involved
      in tissue responses to xenobiotics.

PMID- 7639514
TI  - Antioxidant paradoxes of phenolic compounds: peroxyl radical scavenger and lipid
      antioxidant, etoposide (VP-16), inhibits sarcoplasmic reticulum Ca(2+)-ATPase via
      thiol oxidation by its phenoxyl radical.
AB  - The effectiveness of a phenolic antioxidant as a radical scavenger is determined
      by its reactivity toward peroxyl radicals and also by the reactivity of the anti
      oxidant phenoxyl radical toward oxidation substrate. If the phenoxyl radical
      efficiently interacts with vitally important biomolecules, this interaction may
      result in oxidative damage rather than antioxidant protection. In the present
      work, we studied effects of phenoxyl radicals generated from a phenolic antitumor
      drug, Etoposide (VP-16), on oxidation of thiols and activity of Ca(2+)-ATPase in
      sarcoplasmic reticulum (SR) membranes from skeletal muscles. We found that VP-16
      is an effective scavenger of peroxyl radicals as judged by its ability to inhibit
      a water-soluble azo-initiator, 2,2'-azobis(2-amidinopropane)dihydrochloride
      (AAPH)-induced (i) chemiluminescence (oxidation) of luminol, (ii) fluorescence
      decay (oxidation) of cis-parinaric acid incorporated in SR membranes, and (iii)
      peroxidation of SR membrane lipids. VP-16 did not prevent AAPH-induced oxidation
      of sulfhydryl groups and inhibition of Ca(2+)-ATPase in SR membranes. Electron
      spin resonance measurements showed that AAPH-induced VP-16 phenoxyl radicals were
      reduced by interaction with SR thiols. By using tyrosinase to generate VP-16
      phenoxyl radicals as the only source of free radicals in the model system, we
      found that inhibition of Ca(2+)-ATPase was accompanied by oxidation of about 5
      mol of Ca(2+)-ATPase SH groups per 1 mol of oxidized VP-16. Secondary products of
      VP-16 oxidation (including VP-16 o-quinone) were not efficient in inhibiting SR
      Ca(2+)-ATPase. Reduction of VP-16 phenoxyl radicals by ascorbate protected
      against AAPH- and tyrosinase-induced thiol oxidation and Ca(2+)-ATPase
      inhibition. The results suggest that efficient phenolic scavengers of peroxyl
      radicals such as VP-16--which are commonly considered as potent antioxidants--may
      themselves produce oxidative stress due to secondary reactions of their phenoxyl
      radicals with thiols.

PMID- 7639515
TI  - Fumarate reductase: a target for therapeutic intervention against Helicobacter
      pylori.
AB  - The potential of fumarate reductase as a therapeutic target against the human
      pathogen Helicobacter pylori was investigated by studying the cytotoxicity of
      morantel, oxantel, and thiabendazole, known to inhibit the enzyme in parasitic
      worms. Nuclear magnetic resonance spectroscopy was employed to investigate the
      effects of the inhibitors on the fumarate reductase activity of laboratory
      adapted and wild-type bacterial strains. Production of succinate from fumarate in
      H. pylori cells was inhibited by morantel, oxantel, and thiabendazole. Cell
      growth and viability techniques were used to examine the bacteriostatic and
      bactericidal effects of the three anthelmintics. Each of the antiparasites
      arrested growth and produced cell death in liquid cultures, although the minimal
      inhibitory and bactericidal concentrations of these compounds are such that they
      would not be of therapeutic use. The strength of the effects as measured by
      minimal inhibitory and bactericidal concentrations was oxantel > thiabendazole >
      morantel. The findings suggested that fumarate reductase is an essential
      component of the metabolism of H. pylori and as such constitutes a possible
      target for therapeutic intervention in the treatment of the bacterium.

PMID- 7639516
TI  - Sodium dodecyl sulfate (SDS) activation of the 20S proteasome in rat liver.
AB  - The peptidase activity of the 20S proteasome (multicatalytic protease complex)
      was examined in the 100,000g supernatant fraction prepared from rat liver tissue.
      Fluorogenic substrates for three proteasome peptidase activities were selected on
      the basis of (i) observation of an accelerated degradation in the presence of
      sodium dodecyl sulfate (SDS) and (ii) preferential degradation by the proteasome.
      Peptidase activities were assayed using an immunoprecipitation technique
      utilizing polyclonal antibodies raised against the purified rat proteasome. The
      ability to demonstrate SDS activation of the proteasome is shown to be dependent
      upon the choice of substrate. In addition, among the cytosolic peptidases, the
      property of SDS activation appears to be unique to the proteasome. SDS activation
      profiles were determined for each peptidase activity. Chymotrypsin-like and
      peptidylglutamyl peptide-hydrolyzing activities exhibit a broad plateau of
      activation between 0.04 and 0.05% SDS. Trypsin-like activity exhibits a sharp
      peak of activation at an SDS concentration of 0.04%. The SDS activation profile
      can be altered by changing the protein (proteasome) concentration, i.e.,
      increasing protein (proteasome) concentration of the reaction mixture produces a
      marked rightward shift of the activation profile. On the other hand, changing the
      substrate concentration does not alter the profile. In conclusion, a technique
      for measuring proteasome peptidase activity in the 100,000g supernatant has been
      described. This approach increases the ease of measurement of peptidase activity
      and provides data which may more closely reflect the in vivo activity of the
      proteasome.

PMID- 7639517
TI  - Similar metabolites formed from beta-carotene by human gastric mucosal
      homogenates, lipoxygenase, or linoleic acid hydroperoxide.
AB  - To determine the basis for the formation of excentric cleavage products of beta
      carotene (beta-C) after incubation with human gastric mucosal homogenates, we
      have studied the effect of lipoxygenase in beta-C metabolism. beta-C was
      incubated with human gastric mucosal homogenates, soybean lipoxygenase with
      linoleic acid, or the lipoxygenase primary product, 13(S)-hydroperoxycis,trans
      9,11-octadecadienoic acid (13-LOOH). The beta-C metabolites, beta-apo-14', -12', 
      10', and -8'-carotenals, beta-apo-13-carotenone, retinoic acid, and retinal were
      detected and quantified by HPLC after a 30-min incubation with 1.8 microM beta-C.
      The products from the lipoxygenase plus linoleic acid incubation and from the
      lipoxygenase primary product, 13-LOOH, with beta-C were exactly the same as the
      products from a human gastric mucosal homogenate incubation. Significantly larger
      amounts of the same beta-C metabolites were formed when beta-C was incubated with
      gastric mucosal homogenates and lipoxygenase together. Furthermore,
      nordihydroguaiaretic acid (NDGA), a specific lipoxygenase inhibitor, was found to
      significantly inhibit the formation of beta-apo-carotenoids and retinoids
      produced by gastric mucosal homogenates incubated with beta-C. The similarity of
      the beta-C metabolites when beta-C was incubated with human gastric mucosal
      homogenate, lipoxygenase plus linoleic acid, or 13-LOOH and the inhibition of
      beta-C metabolite production by NDGA in gastric tissue incubation with beta-C
      suggest that lipoxygenase is involved in beta-C metabolism in gastric mucosa. The
      activity of 13-LOOH in our hands would indicate that an enzyme-linked process is
      occurring in gastric tissue producing fatty acid hydroperoxides, and that the
      hydroperoxide, or a radical species derived from it, is able to carry out the
      oxidation of beta-C independently of the enzyme.

PMID- 7639518
TI  - Role of carbohydrates in oxidative modification of fibrinogen and other plasma
      proteins.
AB  - Oxidative stress is related to the mechanism of oncogenesis, cell death, and the
      pathogenesis of many human diseases. Proteins are important targets for oxidative
      modification, and a Western blot assay that can identify individual oxidized
      proteins in whole tissue extracts has been described. Using that assay, it was
      found that plasma proteins show different susceptibilities to oxidative
      modification. Here, we examine the possibility that the carbohydrate groups of
      glycoproteins may contribute to the assessment of protein oxidation by carbonyl
      assays. We used fibrinogen as a model because it is highly susceptible to
      oxidative modification and contains subunits that are differentially
      glycosylated. When oxidation-induced carbonyls were measured in fibrinogen
      subunits by Western blot immunoassay, it was found that the A alpha-chains, which
      contain no associated carbohydrate groups, were most highly oxidized while the B
      beta- and gamma-chains, which are glycosylated, were oxidized far less. However,
      no major difference in the oxidation pattern was obtained when fibrinogen was
      deglycosylated prior to or after exposure to oxidants. This argues against a
      possible protective role of the carbohydrate moieties in oxidation of the
      different fibrinogen subunits. Similar results were obtained with purified human
      immunoglobulin G and transferrin as well as whole plasma. The results show that
      carbohydrate moieties are not good targets for oxidative attack by metal
      catalyzed oxidation systems. Oxidant-induced carbonyl formation in glycoproteins
      derives largely, if not entirely, from amino acid oxidation and not from
      oxidation of carbohydrate groups.

PMID- 7639519
TI  - Yeast protein geranylgeranyltransferase type-I: overproduction, purification, and
      characterization.
AB  - Protein geranylgeranyltransferase type-I (PGGTase-I) catalyzes alkylation of the
      cysteine residue in proteins containing a consensus C-terminal CaaX sequence
      ending in leucine by the C20 hydrocarbon moiety in geranylgeranyl diphosphate
      (GGPP). The Saccharomyces cerevisiae genes encoding the alpha (RAM2) and beta
      (CDC43) subunits of PGGTase-I were translationally coupled by overlapping the
      RAM2-CDC43 stop-start codons and by locating a ribosome-binding site near the 3'
      end of RAM2. Recombinant PGGTase-I was overproduced in Escherichia coli to give
      approximately 8% of total cellular protein and purified 12-fold to > 95%
      homogeneity in two steps by ion-exchange and immunoaffinity chromatography. The
      purified heterodimer contained alpha- and beta-subunits with molecular masses of
      34 and 42 kDa, respectively. A continuous fluorescence assay was developed to
      measure PGGTase-I activity. The recombinant enzyme showed maximal activity at pH
      7.5 and required both Mg2+ and Zn2+. Michaelis constants for GGPP (1.0 microM)
      and dansyl-Gly-Cys-Ile-Ile-Leu (2.4 microM) were similar to those reported for
      yeast protein farnesyltransferase (PFTase) with farnesyl diphosphate and dansyl
      Gly-Cys-Val-Ile-Ala; Vmax = 0.20 mumol min-1 mg-1 for recombinant yeast PGGTase-I
      was similar to that reported for yeast PFTase.

PMID- 7639520
TI  - Characterization, subcellular localization, and developmental regulation of a
      cysteine proteinase from Dictyostelium discoideum.
AB  - Previous studies showed that vegetative cells of Dictyostelium discoideum make a
      cysteine proteinase called proteinase-1, which contains multiple residues of
      GlcNAc-1-P linked directly to peptidyl serines. As a prelude to understanding the
      function of this novel carbohydrate modification, we purified and extensively
      characterized this proteinase in terms of its enzymatic activity, subcellular
      localization, and developmental regulation. The purified enzyme has an apparent
      molecular weight of 38 kDa in heat-denatured, reducing SDS/PAGE and 55 kDa under
      nonreducing conditions. Native gel electrophoresis and isoelectric focusing
      revealed two protein bands with equal activity and having pI values of 2.5 and
      2.6. Even more complex patterns are found in non-heat-denatured SDS/PAGE gels.
      However, partial amino acid sequencing of the purified protein gave predominantly
      a single sequence. The enzyme is inhibited by trans-epoxysuccinyl-L-leucylamido
      (4-guanidino) butane, Na-p-tosyl-L-lysine chloromethyl ketone, N-tosyl-L
      phenylalanine chloromethyl ketone, and leupeptin, has a pH optimum of 5.0, and
      cofractionates with lysosomal enzymes in bacterially grown cells. It appears to
      comprise about 90% of the total cysteine proteinase activity in cells at a time
      when the cells have just finished clearing the bacterial lawn. Prior to this
      point and after the onset of development, its level is 2- to 20-fold lower. This
      remarkably fine regulation parallels the developmental regulation of other
      cysteine proteinases in Dictyostelium. Based on these results it appears that
      proteinase-1 may be primarily used for specialized proteolysis just before the
      onset of development rather than for simply digesting the bacteria for food.

PMID- 7639521
TI  - Effects of long-chain acyl-coenzyme A's on the activity of the soluble form of
      nicotinamide adenine dinucleotide phosphate-specific isocitrate dehydrogenase
      from lactating bovine mammary gland.
AB  - The cytosolic form of NADP+:isocitrate dehydrogenase, a primary source of the
      NADPH required for de novo fatty acid synthesis in lactating bovine mammary
      gland, was studied to determine possible mechanisms of regulation by fatty acyl
      coenzyme A (CoA). The reduction of NADP+ by the enzyme is inhibited by palmitoyl
      CoA. In steady-state experiments, when added enzyme is used to start the
      reaction, analyses of velocity versus palmitoyl-CoA concentration as a binding
      isotherm, following the assumptions of Wyman's theory of thermodynamic linkage,
      suggested that binding of palmitoyl-CoA produced two different inhibitory effects
      on the enzyme. This analysis suggested inhibition first through binding to sites
      with an average dissociation constant of 3.3 microM, then by binding to sites
      with an average dissociation constant of 294 microM. When the enzyme is
      preincubated with palmitoyl-CoA there is an induction of a significant lag-burst
      reaction rate (hysteretic kinetics). Preincubation of the enzyme with its
      substrate, metal-isocitrate complex, nearly abolished the lag time and decreased
      the degree of inhibition. Changes in lag time and percentage inhibition as a
      function of concentration of palmitoyl-CoA followed patterns, similar to those
      observed in steady-state reactions, where the enzyme is not preincubated.
      Examination of the effect of acyl chain length at 300 microM demonstrated that
      only long-chain CoA's with carbon numbers > 14 have pronounced effects on
      kinetics. CoA alone has little or no effect, while stearoyl-CoA completely
      inhibited the enzyme. Other C18 acyl groups produced varying effects depending on
      the degree of unsaturation and cis-trans isomerism. NADP+:Isocitrate
      dehydrogenases, from other sources including that from Escherichia coli, do not
      show such sensitivity to acyl chain character under these conditions.
      Concentration ranges observed for these transitions are compatible with
      physiological conditions. This suggests that complexes of acyl-CoA's and
      NADP+:isocitrate dehydrogenase, in tissue rich in the cytoplasmic form of the
      enzyme, could be related to cytoplasmic events in the synthesis and secretion of
      lipid and possibly protein, since palmitoyl-CoA is known to promote secretory
      processes through acylation reactions which lead to vesicle fusion.

PMID- 7639522
TI  - Fructated protein is more resistant to ATP-dependent proteolysis than glucated
      protein possibly as a result of higher content of Maillard fluorophores.
AB  - Glycation by fructose (fructation) renders bovine serum albumin more refractory
      to degradation by an ATP-dependent proteolytic system from reticulocytes than
      glycation by glucose (glucation). It appears that the decrease in the protein's
      susceptibility to degradation is a complex effect of the various protein-bound
      moities that are generated at the different stages of the Maillard reaction and
      not only the result of primary amino group blockage. Advanced Maillard reaction
      fluorescent components may induce a decrease in proteolysis, whereas the
      intermediate Amadori groups possibly may enhance degradation. However, the
      inhibitory effect on degradation of the fluorophores would predominate at higher
      levels of glycation. Resistance of intracellular fructated proteins to ATP
      dependent degradation may lead to alterations in the function of cells with an
      active sorbitol pathway and, in this way, underlie the complications of diabetes.

PMID- 7639523
TI  - Expression and characterization of a single recombinant proteoglycan tandem
      repeat domain of link protein that binds zinc and hyaluronate.
AB  - The first proteoglycan tandem repeat (PTR) of bovine link protein has been cloned
      in the pMAL-c vector and overexpressed in fusion with maltose-binding protein
      (MBP) in Escherichia coli. The fusion protein can be isolated from the soluble
      phase of the bacterial lysate by amylose affinity chromatography. The PTR domain
      can be cleaved from the MBP domain with factor Xa protease. Evidence using zinc
      affinity chromatography is presented which indicates that at least one of the
      zinc-binding sites of bovine link protein is contained within the first PTR
      domain. Zinc affinity chromatography was then incorporated as the final
      purification step of the MBP/PTR protein. Evidence for the binding of MBP/PTR to
      hyaluronic acid (HA) is demonstrated by coprecipitation with HA using
      cetylpyridinium chloride. Binding is specific since MBP/PTR does not
      coprecipitate with chondroitin sulfate. Binding is also demonstrated in an ELISA
      assay on HA-coated plates. In this assay, binding could be inhibited by the
      addition of HA or HA oligosaccharides.

PMID- 7639524
TI  - Short-chain 3-hydroxy-2-methylacyl-CoA dehydrogenase from rat liver: purification
      and characterization of a novel enzyme of isoleucine metabolism.
AB  - Short-chain L-3-hydroxy-2-methylacyl-CoA dehydrogenase (SC-HMAD), a soluble
      mitochondrial enzyme, was purified 6000-fold from rat liver in 6% yield by a six
      step purification procedure. The purified enzyme was homogenous as judged by gel
      electrophoresis in the presence of sodium dodecyl sulfate. The molecular mass of
      this protein was estimated to be 28 kDa under denaturing conditions. Under
      nondenaturing conditions, the enzyme behaved on Sephacryl S-200 like serum
      albumin with a molecular mass of 66 kDa. Thus, SC-HMAD seems to be a dimer
      composed of two, most likely identical 28-kDa subunits. Immunoblotting with
      antibodies to pig heart L-3-hydroxyacyl-CoA dehydrogenase (HAD) (EC 1.1.1.35)
      revealed that SC-HMAD and HAD are immunologically unrelated proteins. SC-HMAD,
      but not HAD, catalyzes the NAD(+)-dependent dehydrogenation of L-3-hydroxy-2
      methybutyryl-CoA, a metabolite of isoleucine, to 2-methylacetoacetyl-CoA.
      Relative activities with 3-hydroxy-2-methylacyl-CoA thioesters having acyl chains
      with 4, 5, 10, and 16 carbon atoms are 88, 100, 16, and 0%, respectively.
      Unbranched 3-hydroxyacyl-CoA thioesters are also substrates of SC-HMAD, although
      poorer ones as evidenced by apparent Km values of 5 and 19 microM for L-3-hydroxy
      2-methylbutyryl-CoA and L-3-hydroxybutyryl-CoA, respectively. Maximal velocities
      observed with these two substrates were similar. It is concluded that SC-HMAD
      catalyzes the second dehydrogenation step during the beta-oxidation of the
      isoleucine metabolite 2-methylbutyryl-CoA. This enzyme may also be involved in
      the beta-oxidation of natural and xenobiotic branched chain carboxylic acids.

PMID- 7639525
TI  - Mitochondrial beta-oxidation of 2-methyl fatty acids in rat liver.
AB  - The mitochondrial beta-oxidation of 2-methyl fatty acids was studied with coupled
      rat liver mitochondria and purified enzymes. Measurements of mitochondrial
      respiration supported by 2-methyl fatty acids, straight chain fatty acids, or
      their coenzyme A (CoA) thioesters revealed that free short-chain and medium-chain
      2-methyl fatty acids are oxidized nearly or as efficiently as are their straight
      chain analogs. Long-chain 2-methyl hexadecanoyl-CoA is also oxidized, although
      more slowly than its unbranched counterpart. However, medium-chain 2
      methyldecanoyl-CoA, in contrast to its unbranched analog, is not oxidized at all.
      Of all acyl-CoA dehydrogenases only long-chain acyl-CoA dehydrogenase acts on
      medium-chain and long-chain 2-methylacyl-CoA thioesters. The resultant 2-methyl-2
      enoyl-CoA thioesters are substrates of the mitochondrial trifunctional beta
      oxidation complex which catalyzes the sequential hydration, dehydrogenation, and
      thiolytic cleavage of 2-methyl-substituted substrates to yield chain-shortened
      acyl-CoA thioesters and propionyl-CoA. The matrix enzymes L-3-hydroxyacyl-CoA
      dehydrogenase and 3-ketoacyl-CoA thiolase, in contrast to enoyl-CoA hydratase,
      are inactive with medium-chain and long-chain 2-methyl-substituted chain
      substrates. The specificity of the beta-oxidation enzymes toward 2-methyl
      branched substrates forms the basis for assays of long-chain acyl-CoA
      dehydrogenase and the trifunctional beta-oxidation complex in the presence of
      their mitochondrial isozymes. It is concluded that rat liver mitochondria can
      oxidize 2-methyl fatty acids, but does so most effectively with medium-chain and
      short-chain ones that can enter mitochondria directly in a carnitine-independent
      manner.

PMID- 7639526
TI  - Site-specific mutagenesis demonstrates that the structural requirements for
      efficient electron transfer in Anabaena ferredoxin and flavodoxin are highly
      dependent on the reaction partner: kinetic studies with photosystem I,
      ferredoxin:NADP+ reductase, and cytochrome c.
AB  - Electron transfer reactions involving site-specific mutants of Anabaena
      ferredoxin (Fd) and flavodoxin (Fld) modified at surface residues close to the
      prosthetic groups, with photoexcited P700 in spinach photosystem I (PSI)
      particles, ferredoxin:NADP+ reductase (FNR), and horse cytochrome c (cytc), have
      been investigated by laser flash photolysis and stopped-flow spectrophotometry.
      Nonconservative mutations in Fd at F65 and E94, which have been shown to result
      in very large inhibitions of electron transfer to FNR, were found to yield wild
      type behavior in reactions with PSI and cytc. In general, the effects of Fd
      mutagenesis on the PSI reactions were considerably smaller than those observed
      for the FNR reaction. In the case of Fld, mutagenesis was found to have only
      small effects on both the FNR and PSI reactions, although the specific sites
      whose mutation caused changes in electron transfer properties differed for the
      two systems. In contrast, several of the Fld mutants showed appreciably larger
      effects on the nonphysiological reaction with cytc. We conclude from these
      studies that the structural requirements for efficient electron transfer
      involving the Fd and Fld molecules differ, depending upon the reactant with which
      these redox proteins interact. This is consistent with the multiple roles that
      these proteins have in vivo in biological electron transfer and implies that
      different conserved residues in these proteins have evolved to satisfy varying
      requirements of particular reaction partners.

PMID- 7639527
TI  - Dissociation of dimeric 6-hydroxymellein synthase, a polyketide biosynthetic
      enzyme in carrot cell extracts, with loss of keto-reducing activity.
AB  - 6-Hydroxymellein synthase, an inducible polyketide biosynthetic enzyme in carrot
      cell extracts, is composed of two identical subunits, and the homodimer is
      dissociated to monomeric peptides under high-ionic-strength conditions with loss
      of the synthase activity. Appreciable radioactivities were associated with the
      synthase proteins when the monomer enzyme was incubated with the radiolabeled
      substrates, acetyl-coenzyme A (CoA) and malonyl-CoA. Therefore, it appeared that
      the synthase does not lose the ability of binding the substrate even after the
      dissociation to monomers. The monomeric synthase liberated triacetic acid lactone
      as the derailment product instead of 6-hydroxymellein from the enzyme-attached
      triketomethylene chain which is the immediate precursor of an NADPH-dependent
      keto-reducing reaction involved in 6-hydroxymellein biosynthesis. These
      observations strongly suggest that the monomeric synthase retains the ability of
      ketomethylene chain elongation by the condensation of acyl-CoAs, but is lacking
      in an NADPH-dependent keto-reducing activity toward the triketide intermediate.
      Results obtained in the present experiments imply that the catalytic domain of
      acyl-CoA condensation is able to associate with that of keto reduction, possibly
      belonging to another subunit, only in the homodimeric structure to organize the
      multicatalytic reaction center.

PMID- 7639528
TI  - Oxidative conversion of thiocyanate to cyanide by oxyhemoglobin during acid
      denaturation.
AB  - Human oxyhemoglobin (Hb-O2) converts thiocyanate to cyanide under acidic
      conditions, in a hemoglobin and thiocyanate concentration-dependent manner. Other
      naturally occurring hemoglobin derivatives and hematin did not result in cyanide
      producing activity. Pre-denaturation completely destroyed cyanide production. In
      the presence of 10% phosphoric acid, 12 microM cyanide was produced by 1 mM Hb-O2
      (per heme) and 1 mM thiocyanate. This conversion was observed over a wide range
      of acidic pH levels at 50 degrees C, with an optimal pH of 4. The production of
      cyanide under strong acidic conditions was completed within 1 s, while under weak
      acidic conditions (pH approximately 5) the production gradually increased for
      half an hour. Under both conditions, the time course for cyanide production
      coincided with the disappearance of this converting activity. Thiocyanate
      conversion by acidified Hb-O2 was completely suppressed by the addition of
      ascorbic acid, significantly suppressed by superoxide anion radical (O2-)
      scavengers or thiourea, but not effected by scavengers of hydroxyl radical,
      singlet oxygen, and protein radical. In addition to acidification, other
      processes for denaturation of Hb-O2 resulted in detectable production of cyanide,
      e.g., heating, extraction by organic solvents, and incubation with denaturating
      or oxidative reagents. These data suggest that O2- generated during Hb-O2
      denaturation and also a hydroperoxyl radical converted under acidic conditions
      are the oxidizing species that convert thiocyanate to cyanide.

PMID- 7639530
TI  - NF-kappa B transcription factor activation by hydrogen peroxide can be decreased
      by 2,3-dihydroxybenzoic acid and its ethyl ester derivative.
AB  - Reactive oxygen species like hydrogen peroxide (H2O2) have been shown to serve as
      messengers in the induction of NF-kappa B and, hence, in the activation and
      replication of human immunodeficiency virus type 1 (HIV-1) in human cells.
      Several antioxidant compounds and iron chelators have been shown to interfere
      with both NF-kappa B and HIV-1 activation under oxidative stress. Because 2,3
      dihydroxybenzoic acid (DHB) and its ethyl ester derivative (DHB-EE) are potent
      oral iron chelators, we started to investigate their effects on monocytes treated
      with increasing H2O2 concentrations. These two compounds exert important
      protective effects against the cytotoxic effect of H2O2 as 300 microM DHB or DHB
      EE increased cell survival from 30 to 85%. The treatment of monocytes with
      increasing amounts of H2O2 (from 0 to 3 mM) leads to the nuclear induction of NF
      kappa B which is dose dependently inhibited by both DHB and DHB-EE. Addition of
      ferric ions to DHB only partially restores the NF-kappa B induction by H2O2,
      while this effect is almost completely restored by ferric ion addition to DHB-EE.
      Using spin trapping coupled to electron spin resonance, we have demonstrated that
      DHB and, to a lesser extent, DHB-EE trapped hydroxyl radicals produced by H2O2
      photolysis. These data demonstrate that small aromatic molecules harboring both
      iron-chelating and antioxidant properties like DHB and DHB-EE can effectively
      interfere with the deleterious effects of H2O2 in monocytes where iron overload
      can be observed in HIV-1-infected patients.

PMID- 7639529
TI  - Mutagenic activation of 3-methoxy-4-aminoazobenzene by mouse renal cytochrome
      P450 CYP4B1: cloning and characterization of mouse CYP4B1.
AB  - A new P450 responsible for mutagenic activation of 3-methoxy-4-aminoazobenzene (3
      MeO-AAB) which is a potent procarcinogen was purified from renal microsomes of
      male mice using an index of umu gene expression. The purified P450 had high
      bioactivation toward 3-MeO-AAB and also 2-aminofluorene and 2-aminoanthracene.
      The antibody against this P450 completely inhibited mutagenic activation of 3-MeO
      AAB of mouse renal microsomes. With immunoblotting, this form was present
      abundantly in renal microsomes of male mice but not in those of female mice. This
      P450 was also present in pulmonary microsomes of male and female mice but not in
      hepatic microsomes. The NH2-terminal amino acid sequence analysis indicated that
      this form belonged to the CYP4B subfamily. Thus, mouse kidney cDNA library was
      screened with rat CYP4B1 probe. The cDNA-deduced amino acid sequence of isolated
      cDNA consisted of 511 amino acids and bore 90, 86, and 84% similarities to rat,
      rabbit, and human CYP4B1, respectively. The NH2-terminal amino acid sequence of
      the purified renal P450 and amino acid sequence of BrCN-digested peptides from
      the purified P450 agreed with the cDNA-deduced amino acid sequence. These results
      suggest that CYP4B1 is a major form in renal microsomes of male mice and plays a
      major role in mutagenic activation of 3-MeO-AAB. In extrahepatic tissue, CYP4B1
      may contribute to chemical carcinogenesis.

PMID- 7639531
TI  - A cationic manganic porphyrin inhibits uptake of paraquat by Escherichia coli.
AB  - A manganic porphyrin (MnTMPyP), which catalyzed the dismutation of O2-,
      facilitated the aerobic growth of a sodA sodB strain of Escherichia coli and
      protected a superoxide dismutase (SOD)-competent parental strain against
      paraquat. Surprisingly, the latter effect was more complete than the former and
      the mimic could block the inductions of fumarase C and of glucose 6-phosphate
      dehydrogenase by paraquat, even though SOD could not. An explanation for these
      apparent paradoxes was found in the ability of MnTMPyP to inhibit the uptake of
      paraquat by E. coli. MnTMPyP was accumulated by E. coli until its intracellular
      concentration was 20-fold greater than the extracellular concentration. This
      happened in a glucose plus salts medium, but not from a rich LB medium. MnTMPyP
      was bound onto cellular macromolecules and was maintained in the reduced state
      within E. coli. The free form of the reduced MnTMPyP was autoxidizable, but the
      bound form was not. Consequently, the free form could catalyze the oxidation of
      ascorbate, while the bound form did not.

PMID- 7639532
TI  - Spin trap studies on the decomposition of peroxynitrite.
AB  - The observation of the hydroxyl radical spin adduct of 5,5-dimethyl-1-pyrroline-N
      oxide (DMPO) is evaluated as a probe for the production of hydroxyl radicals from
      the decomposition of peroxynitrite. Although a weak signal corresponding to the
      DMPO-hydroxyl radical spin adduct (.DMPO-OH) is observed when peroxynitrite is
      allowed to decompose in the presence of DMPO, it is concluded that this does not
      constitute proof of the presence of free hydroxyl radicals. The observed rate
      constant for the decay of peroxynitrite increases from 0.35 to 0.51 s-1 (46%
      increase) when the concentration of DMPO is increased from 0 to 75 mM. This
      strongly suggests there is a reaction between DMPO and HOONO, or between DMPO and
      an activated intermediate of HOONO, to produce the hydroxyl radical spin adduct.
      The addition of glutathione or cysteine produces a large increase in the
      intensity of the .DMPO-OH spin adduct signal; experiments employing superoxide
      dismutase suggest that the increases in the amounts of .DMPO-OH adduct are
      produced from the decomposition of the spin adduct of the superoxide radical
      (.DMPO-OOH). The superoxide adduct arises as a result of the autoxidation of
      thiols, a process known to produce superoxide. The results presented here are
      incompatible with the formation of free hydroxyl radicals but can be explained in
      terms of an intermediate of HOONO that is less reactive and more selective than
      the free hydroxyl radical.

PMID- 7639533
TI  - Affinity binding of distinct functional fibronectin domains to immobilized metal
      chelates.
AB  - Fibronectin has been found to bind metal ions. Using metal chelate chromatography
      and limited proteolysis to generate the distinct functional domains of
      fibronectin we set out to address the metal binding sites to well-defined regions
      of fibronectin. The results show that the affinity binding of fibronectin to Co2+
      is mediated exclusively via the collagen binding domain of the molecule, whereas
      fibronectin will bind to Zn2+, Ni2+, and Cu2+ by metal binding sites located in
      two, three, and four well-defined regions of fibronectin, respectively. Fe2+ and
      Mn2+ chelates did not bind any of the isolated fibronectin domains. Combined
      metal chelate affinity chromatography opens a possibility to isolate particular
      fibronectin domains.

PMID- 7639534
TI  - Oxidative damage to extracellular fluids by ozone and possible protective effects
      of thiols.
AB  - Environmental levels of ozone (O3) frequently exceed air quality standards in
      many urban areas, and much research has been devoted to pathophysiological
      effects of O3 inhalation. Inhaled O3 will interact primarily with respiratory
      tract lining fluids (RTLF) and with constituents therein. It is believed that
      interaction of O3 with constituents in RTLF occurs by reactive absorption. We
      investigated interactions of O3 with human blood plasma, used as a model
      extracellular fluid representing RTLF, and studied oxidation of plasma
      antioxidants, proteins, and lipids. Plasma was exposed to various concentrations
      of O3 in humidified air, supplied at a continuous flow, in a system that mimics
      exposure of RTLF to inhaled O3 in vivo. Interaction of O3 with plasma appeared to
      be caused by reactive absorption of O3 by plasma. It was found that O3 reacts
      primarily with the aqueous antioxidants ascorbate and urate. Reactive absorption
      of O3 by plasma ascorbate and urate was found to be more efficient at low (2 ppm)
      O3 levels than at high (16 ppm) levels. We were also able to detect oxidative
      damage to plasma proteins and lipids after prolonged exposure to O3. Second, we
      investigated whether GSH or dihydrolipoic acid (DHLA) could prevent oxidative
      damage to plasma proteins and lipids by O3, under our exposure conditions. In
      contrast to plasma, RTLF contain relatively high amounts of GSH, which may
      contribute to antioxidant protection to respiratory tract epithelial cells. DHLA
      is an endogenous dithiol and has potent antioxidant properties. Addition of
      either GSH or DHLA to plasma (at concentrations up to 1 mM) prior to O3 exposure
      did not inhibit oxidation of plasma proteins and lipids during exposure to O3,
      nor did it attenuate depletion rates of ascorbate or urate. Our results indicate
      that added thiols cause increased reactive absorption of O3, rather than
      preventing reaction of O3 with other plasma constituents. Thiol supplementation
      could afford protection against O3-induced injury in vivo by increasing reactive
      absorption of O3 in the upper respiratory tract, thereby protecting the epithelia
      of lower airways and gas-exchanging portions of the lungs from exposure to toxic
      levels of O3.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7639535
TI  - Production of hydroxyl radical by iron(III)-anthraquinone complexes through self
      reduction and through reductive activation by the xanthine oxidase/hypoxanthine
      system.
AB  - The iron(III) complexes of doxorubicin and epirubicin were observed to undergo a
      self-reduction (autoxidation) reaction in the absence of added reductants under
      aerobic conditions that resulted in the formation of ferrous anthracycline
      complexes. These self-reduction reactions resulted in significant hydrogen
      peroxide-mediated hydroxyl radical formation, as determined by electron
      paramagnetic resonance spin trapping. In contrast, the iron(III) complexes of
      daunorubicin, idarubicin, and mitoxantrone produced no significant amount of
      hydroxyl radical formation. Only the anthraquinones with an alpha-ketol side
      chain were observed to undergo both self-reduction and hydroxyl radical
      formation. Thus, the alpha-ketol side chain must be undergoing concomitant
      oxidation. The rate of self-reduction of the iron(III)-doxorubicin complex is
      consistent with a mechanism in which unbound doxorubicin binds to an iron(III)
      doxorubicin complex of decreased coordination and after binding undergoes an
      intramolecular electron transfer. Molecular modeling was used to identify
      iron(III)-doxorubicin complexes that could result in electron transfer from the
      doxorubicin side chain hydroxyl group to the iron(III). All of the iron(III)
      anthracycline complexes were able to produce hydroxyl radicals at significantly
      increased rates in the presence of the xanthine oxidase/hypoxanthine superoxide
      generating system. In this system the iron(III)-epirubicin complex gave the
      greatest rate of hydroxyl radical production, with iron(III)-idarubicin giving
      the least.

PMID- 7639536
TI  - Glutathione redox cycle-driven recovery of reduced glutathione after oxidation by
      tertiary-butyl hydroperoxide in preimplantation mouse embryos.
AB  - The purpose of this study was to determine whether mouse embryos at the two-cell
      to blastocyst stage have the capacity to reduce glutathione disulfide (GSSG) and
      to elucidate the mechanism that embryos utilize to recover from tertiary-butyl
      hydroperoxide (tBH)-induced oxidative stress. Experiments were conducted on
      embryos in vitro and tBH was used to induce oxidation of embryonic reduced
      glutathione (GSH). After derivatization of extracted embryo samples with dansyl
      chloride, GSH and GSSG were measured at picomole levels by fluorometric HPLC. Two
      cell- and blastocyst-stage embryos were able to recover their GSH levels within
      45 min after depletion of GSH by incubation in tBH for 15 min. Addition of 1,3
      bis(2-chloroethyl)-1-nitrosourea to the culture medium blocked recovery of GSH
      and resulted in continued elevation of GSSG. Addition of buthionine sulfoximine
      (BSO) to the culture medium did not affect GSH levels in two-cell-stage embryos,
      but did reduce GSH levels in blastocysts by 1.5 h. Culture of two-cell embryos in
      the presence of BSO for 45 h decreased embryonic GSH content and percentage of
      embryos developing to the blastocyst stage. These results indicate that
      preimplantation mouse embryos have the capacity to reduce GSSG and suggest that
      under normal conditions, depletion and synthesis of GSH occur to a greater extent
      in the blastocyst than in the two-cell-stage embryo. A major protective role for
      glutathione reductase during specific stages of embryo development is indicated.

PMID- 7639537
TI  - Oxaloacetate decarboxylase: on the mode of interaction with substrate-mimetic
      affinity ligands.
AB  - The mode of interaction of the ketocarboxyl-group-recognizing enzyme oxaloacetate
      decarboxylase (OXAD) from Pseudonomas sp., with purpose-designed (keto)-carboxyl
      terminal biomimetic monochlorotriazinyl-dyes (BM) and parent dichlorotriazinyl
      dye Vilmafix blue A-R (VBAR) was investigated. Kinetic inhibition studies and
      determinations of KD values of the respective dye-enzyme complex from both
      difference spectra and enzyme inactivation studies were employed.
      Substratemimetic (biomimetic) dye-ligands bear a terminal (keto)carboxyl-moiety
      linked to the reactive chlorotriazine ring, thus mimicking the organic acid
      substrate of OXAD. Dichlorotriazine-dye VBAR bound specifically and irreversibly
      to OXAD (k3 0.22 min-1). The inactivation of OXAD by VBAR was enhanced in the
      presence of 1 mM Mn+2 (KD 67.2 microM) but in the absence of metal cation was
      decreased (KD 117 microM). The metal cation behaves as a partial competitive
      activator. Either of binary complexes dye.OXAD and OXAD.Mn+2 could be formed
      first, prior to addition of the third constituent to form the ternary complex,
      although the former route may be favored. The pKa of the catalytically important
      nucleophile, involved in the specific modification of OXAD, was calculated to
      7.4. Biomimetic monochlorotriazine dyes have failed to inactivate OXAD but
      inhibited competitively the inactivation by VBAR. When compared to commercial
      VBAR and Cibacron blue 3GA (CB3GA), all BM ligands show lower KD values,
      therefore, higher affinity for the enzyme. OXAD preferred binding to BM dyes
      which exhibited a large aliphatic ketocarboxyl-terminal biomimetic moiety. Dye
      binding to OXAD was accompanied by a characteristic spectral change in the range
      550-800 nm. Electrostatic interactions appeared to play a dominant role in the
      dye.OXAD complex. The BM ligand bearing an aminoethyloxamate as its terminal
      biomimetic moiety (BM7) displayed the highest affinity (KD 0.5 or 7.0 microM;
      approx 10-fold decrease over CB3GA). The BM7 ligand behaved as competitive
      inhibitor (Ki 98 microM) of oxaloacetate decarboxylase against oxaloacetate as
      variable substrate.

PMID- 7639538
TI  - Characterization of the substrate specificity of sucrose-phosphate synthase
      protein kinase.
AB  - Sucrose-phosphate synthase (SPS; EC 2.4.1.14) is regulated by reversible protein
      phosphorylation. When the enzyme is phosphorylated it is inactivated and can be
      reactivated by removal of phosphate. The major regulatory phosphorylation site is
      known to be Ser158 in the spinach-leaf enzyme, and two protein kinase activities
      have been resolved chromatographically which phosphorylate SPS at this site in
      vitro. In this report, we use a set of synthetic peptide substrate analogs based
      on the phosphorylation site sequence, and a set of Escherichia coli-expressed 26
      kDa fragments of spinach SPS which contain the site, to identify the recognition
      elements that target the two protein kinases to Ser158. The major recognition
      element consists of basic residues at P-3 and P-6 relative to the phosphorylated
      serine. Comparison of the spinach enzyme amino-acid sequence with two other plant
      species show conservation of these amino acids and implies that these signals are
      also conserved. We also present evidence that glucose-6-phosphate is not only an
      allosteric activator of SPS but also an inhibitor of SPS-protein kinase per se,
      thereby allowing it to act at both levels of SPS regulation.

PMID- 7639539
TI  - A site-directed mutagenesis study at Lys-113 of NAD(P)H:quinone-acceptor
      oxidoreductase: an involvement of Lys-113 in the binding of the flavin adenine
      dinucleotide prosthetic group.
AB  - NAD(P)H: quinone-acceptor oxidoreductase (EC 1.6.99.2), also referred to as DT
      diaphorase, is a flavoprotein that catalyzes the two-electron reduction of
      quinones and quinonoid compounds to hydroquinones, using either NADH or NADPH as
      the electron donor. Using an Escherichia coli expression system developed
      previously, we prepared three mutants of the rat liver quinone reductase. These
      mutants are Lys-113-His (K113H), Lys-113-Asp (K113D), and Lys-113-Ala (K113A).
      While the mutant K113H was readily purified using the same procedure as for the
      purification of the wild-type quinone reductase and found to have an activity
      similar to that of the wild-type enzyme, K113D and K113A were purified only in
      very small quantities, mainly in the form of apoprotein, and had very low
      activities. The results suggest that a positively charged amino acid at this
      position is important for the binding of the flavin adenine dinucleotide (FAD)
      prosthetic group. Flavin spectral studies of 6-mercapto-FAD-reconstituted mutants
      revealed that mutation at Lys-113 affects the protein environment around position
      6 of the isoalloxazine ring.

PMID- 7639540
TI  - Evaluation of the cell specificity and sulfate dependence of glomerular
      extracellular matrix proteoglycan synthesis.
AB  - Homogeneous cultures of epithelial, endothelial, and mesangial cells from calf
      glomeruli were radiolabeled with [35S]sulfate in order to evaluate their capacity
      for the biosynthesis of the proteoglycan (PG) components present in the
      glomerular extracellular matrix. Although each cell type was observed to
      incorporate into its matrix predominantly immunologically related heparan sulfate
      (HS) PGs (M(r) approximately 500 kDa), endothelial and mesangial cells also
      deposited substantial amounts of PGs with chondroitin sulfate (CS) and dermatan
      sulfate (DS) chains. The limited capacity of epithelial cells to synthesize PGs
      other than those containing HS was also evident from the immunologically distinct
      components (M(r) approximately 300 kDa) shed into the medium which in contrast to
      those from the endothelial and mesangial cells contained no CS and only small
      amounts of DS glycosaminoglycans. While the matrix proteoglycan HS chains
      differed in length depending on cell type, they were similar in containing the
      six mono- and disulfated disaccharide species previously found in bovine
      glomerular basement membrane, including the distinctive iduronic-GlcNSO3 (3-SO4)
      sequences. While the addition of sulfate to medium free of this ion brought about
      no change in HS PG production by any of the three cell types and the formation of
      CS and DS chains by epithelial and mesangial cells was unaffected, the formation
      of CS/DS PGs by endothelial cells was altered to a pronounced extent through the
      conversion of an undersulfated PG to a more polyanionic molecule. Our findings
      are consistent with the concept that the glomerular extracellular matrix is made
      up of two biosynthetically distinct regions (mesangium and basement membrane) and
      are relevant to an understanding of various diseases affecting the renal filter.

PMID- 7639541
TI  - Purification and characterization of Azotobacter vinelandii glucose-6-phosphate
      dehydrogenase: dual coenzyme specificity.
AB  - Azotobacter vinelandii glucose-6-phosphate dehydrogenase isolated from cell
      sonicates was purified 81-fold to electrophoretic homogeneity and a specific
      activity of 73 units/mg protein using ion-exchange and Matrex Dye chromatography.
      Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and molecular exclusion
      chromatography indicated the enzyme to be a tetramer composed of 52,000 M(r)
      subunits. The enzyme utilized both NAD and NADP as coenzymes with Km values of
      220 and 50 microM, respectively. In addition, the purified enzyme functioned well
      with the thionicotinamide analogs of NAD and NADP. A sigmoidal response was
      observed in studies of the effect of glucose 6-phosphate concentration on initial
      velocities. Evidence in support of one enzyme with dual coenzyme specificity was
      obtained in purification, thermodenaturation, and inhibitor studies. The enzyme
      exhibited a pH optimum of 8.5. Coenzyme-competitive inhibition was observed with
      nine adenosine derivatives with no significant selectivity shown for 2'
      phosphoryl derivatives. Ki values for product inhibition by NADH and NADPH were
      higher than the Km values for the respective oxidized forms of the coenzymes.

PMID- 7639542
TI  - James Spence Medallist 1995. Professor Richard H R White.

PMID- 7639543
TI  - Cross sectional stature and weight reference curves for the UK, 1990.
AB  - The current reference curves of stature and weight for the UK were first
      published in 1966 and have been used ever since despite increasing concern that
      they may not adequately describe the growth of present day British children.
      Using current data from seven sources new reference curves have been estimated
      from birth to 20 years for children in 1990. The great majority of the data are
      nationally representative. The analysis used Cole's LMS method and has produced
      efficient estimates of the conventional centiles and gives a good fit to the
      data. These curves differ from the currently used curves at key ages for both
      stature and weight. In view of the concerns expressed about the current curves
      and the differences between them and the new curves, it is proposed that the
      curves presented here should be adopted as the new UK reference curves.

PMID- 7639544
TI  - Body mass index reference curves for the UK, 1990.
AB  - Reference curves for stature and weight in British children have been available
      for the past 30 years, and have recently been updated. However weight by itself
      is a poor indicator of fatness or obesity, and there has never been a
      corresponding set of reference curves to assess weight for height. Body mass
      index (BMI) or weight/height has been popular for assessing obesity in adults for
      many years, but its use in children has developed only recently. Here centile
      curves for BMI in British children are presented, from birth to 23 years, based
      on the same large representative sample as used to update the stature and weight
      references. The charts were derived using Cole's LMS method, which adjusts the
      BMI distribution for skewness and allows BMI in individual subjects to be
      expressed as an exact centile or SD score. Use of the charts in clinical practice
      is aided by the provision of nine centiles, where the two extremes identify the
      fattest and thinnest four per 1000 of the population.

PMID- 7639545
TI  - Screening tests for coeliac disease.

PMID- 7639546
TI  - Recruiting patients to clinical trials: lessons from studies of growth hormone
      treatment in renal failure.
AB  - Issues raised by the recruitment of children to trials of growth hormone
      treatment for short stature in chronic renal failure are reported. Information
      needs of parents and children are discussed, the latter should take account of
      the children's developmental level and anticipated involvement in decision
      making. When the incidence of certain side effects is low and probably
      unquantifiable there are particular problems; failure to include these in
      information sheets may compromise informed consent but inclusion will, at least
      for some families, make an already difficult decision even more complicated. A
      process of recruitment is described which attempts to protect against bias and
      which balances the requirement to impart neutral information with appropriate
      clinical involvement in the decision to enter the study. Other functions of the
      recruitment process are identified. Analysis of understanding and decision making
      demonstrates that good understanding is neither necessary nor sufficient for ease
      of decision making. The recruitment process was time consuming and needs planning
      and funding in future studies. Many of these issues are of general importance for
      trials of treatment in children.

PMID- 7639547
TI  - Short stature and chronic renal failure: what concerns children and parents?
AB  - Multicentre trials are evaluating growth hormone treatment in short children
      (height > 2 SDs below mean) with chronic renal failure (CRF), on dialysis, or
      with a transplant. Thirty children and parents from four centres were interviewed
      to assess psychological functioning and evaluate their concerns about growth in
      the context of CRF. There were 24 males and six females, age range 2-18 years.
      Fifty per cent of patients had additional non-renal complications and 30% had
      learning difficulties. Differences between the respective concerns of parents and
      children were striking. Parents' predominant concern was their child's future
      health (50%) and prospects (37%) while children's main concern was the impact of
      illness on their family (50%). Growth was a major concern for 30% of parents and
      28% of children. Growth problems are important and should be considered within
      the context of other illness issues. Improved understanding of parental and child
      concerns may help maximise the benefits of growth hormone and assist in the
      management of children with CRF.

PMID- 7639548
TI  - Microalbuminuria and nephropathy in insulin dependent diabetes mellitus.

PMID- 7639549
TI  - Development and satisfaction with individual programme planning in a disability
      service.
AB  - A consumer survey of a preschool disability service identified parents who did
      not feel their concerns were fully understood by professionals, nor felt involved
      or in agreement with treatment decisions, nor that services were provided in a
      coordinated way. A system of individual programme planning (IPP) was introduced
      in order to address these issues and other shortfalls of the existing service.
      Information was obtained from 96% of parents and 87% of professionals who
      attended IPP meetings over a four month period. Overall satisfaction was high
      (92% of parents: 96% of professionals). Parents now felt fully involved in
      decision making, 80% felt their views were understood and 100% agreed with
      treatment goals. Dissatisfaction was expressed with meeting attendance, the
      marginalisation of parents, and the timing and chairing of meetings. Consumer
      satisfaction surveys are recommended for use in highlighting areas of service
      shortfall, to direct and evaluate service change, and to monitor quality.

PMID- 7639550
TI  - Impact of functional severity on self concept in young people with spina bifida.
AB  - This study examines the relationship between medical and functional severity of
      disability and levels of self esteem and self concept in 79 young people with
      spina bifida. Greater feelings of global self worth and of self esteem in
      physical appearance were associated with greater severity of disability. This was
      only in part an effect of lower IQ among the most disabled young people. Many of
      the least disabled had marked impairment of self esteem. Analysis of the impact
      of individual aspects of disability confirmed the association between increased
      self esteem in physical appearance and global self worth, and diminished
      functional ability. Academic self ratings, however, were higher in the less
      disabled. Hydrocephalus and continence appeared to have minimal effect on self
      esteem. The relationship between severity of disability in spina bifida and self
      concept is complex and mediated by a range of factors. It is incorrect to assume
      that the psychological impact is less in the mildly disabled young person.

PMID- 7639551
TI  - Visual impairment in severe and profound sensorineural deafness.
AB  - The frequency of reversible and irreversible visual impairment was determined in
      children with severe and profound sensorineural deafness, as subnormal vision can
      adversely affect their educational and social development. Eighty three of 87
      such children attending an audiology service were examined to assess the
      incidence and severity of visual impairment. Each child underwent a detailed
      ophthalmic assessment. The criteria for visual impairment were visual acuity <
      6/9 Snellen or equivalent and/or abnormal binocular vision. Forty five had a
      normal ophthalmic examination (54.2%). Twenty nine had visual impairment (34.9%)
      and nine had ophthalmological abnormalities that did not interfere with vision
      (10.9%). A higher proportion of children with risk factors for visual pathology
      demonstrated visual impairment than those in whom there were no risk factors.
      None the less, 44% of visual impairment was among patients without risk factors.
      The results underline the need to examine all children with severe and profound
      sensorineural deafness soon after diagnosis and indicate that children with
      multiple handicaps have a greater likelihood of visual impairment (11 of 14
      cases).

PMID- 7639552
TI  - Parents' views of health surveillance.
AB  - The aim of the study was to discover the views of parents about the 1991
      Leicestershire child health surveillance programme, its organisation, and
      content. The study design was a postal questionnaire survey to parents of a
      sample of children eligible for the new surveillance programme. One thousand
      parents received questionnaires, of which 66% (660) were returned. Poor access
      for prams and wheelchairs (595 responses) and inadequate general cleanliness (249
      responses) caused most criticism of clinic premises. The experiences of parents
      from ethnic minorities were significantly worse for some professional
      consultation factors, but they received significantly more health advice than
      other parents. Parents lacked sufficient information about the surveillance
      programme and their most frequent reasons for non-attendance were time related
      factors. Minimum standards for child health surveillance premises are required.
      At present, many fail to reach adequate standards of privacy and accessibility.
      Schemes to ensure an equal partnership in child health surveillance between
      parents and professionals are essential.

PMID- 7639553
TI  - Lipid profile with paternal history of coronary heart disease before age 40.
AB  - Serum lipids were measured in children and their parents from 40 families in
      which the father had a myocardial infarction or coronary heart disease (CHD)
      before age 40 years. The relationship between physical activity and serum lipid
      concentrations in the children was also evaluated. Twenty six men had one or more
      abnormal lipid value (in mmol/l): total venous cholesterol (TVC) > 6.24,
      triglycerides < 2.55, low density lipoprotein cholesterol (LDL-C) > 4.42, or high
      density lipoprotein cholesterol (HDL-C) < 0.91. There were 15 spouses with
      significant hyperlipidaemia (values above). In the 107 children examined, TVC
      mean (SD) was 4.68 (1.17), triglycerides 1.4 (0.8), LDL-C 3.0 (1.0), and HDL-C
      1.18 (0.28). Altogether 42% of the children had significant hyperlipidaemia. No
      significant correlation was found between the degree of physical activity of the
      children and their LDL-C and TVC concentrations. However, a significant positive
      correlation was found between the degree of physical activity and HDL-C and a
      significant negative one with triglyceride concentrations. It is concluded that
      screening the progeny of young CHD patients is highly productive in identifying
      young people at excessive risk for future CHD. The data also suggest that
      promoting high degrees of activity among these children may have a positive
      influence on risk factors for adult onset CHD.

PMID- 7639554
TI  - Contemporary results of balloon valvuloplasty and surgical valvotomy for
      congenital aortic stenosis.
AB  - The purpose of this study was to compare contemporary results of balloon
      dilatation and surgery for valvar aortic stenosis in infants and children in the
      five years between August 1988 and October 1993. Thirty four children underwent
      attempted balloon valvuloplasty (age 1 day-16 years, weight 1720 g-68 kg) (group
      1), eight of whom were neonates with critical aortic stenosis. During the same
      period, 17 children underwent direct surgical valvotomy (group 2) (seven
      neonates). Successful balloon valvuloplasty was achieved in 33 (97%) with
      immediate reduction in the instantaneous systolic pressure gradient from 82 to 34
      mm Hg (mean). There were two deaths in this group (both neonates), the second in
      a preterm neonate from necrotising enterocolitis. Complications requiring
      intervention in group 1 were aortic regurgitation in one and femoral artery
      injury in two. Follow up from four months to five years showed sustained results
      in most cases. There were two neonatal deaths in the surgical group. When the two
      groups were compared there was no significant difference in mortality, morbidity,
      or need for reintervention within 12 months. Deaths from both groups were
      attributed to small left ventricles. Hospital stay was significantly shorter in
      group 1. It is concluded that balloon dilatation for valvar aortic stenosis is
      effective and safe for the entire paediatric population. The results compare
      favourably with those of surgery.

PMID- 7639555
TI  - Hydrosonography in the evaluation of colorectal polyps.
AB  - Prewarmed saline enemas and transabdominal ultrasound (hydrosonography) were used
      to evaluate 17 consecutive children with rectal bleeding before colonoscopy.
      Twelve patients with polyps were identified (10 by ultrasound, 10 by endoscopy):
      these included multiple hyperplastic polyps (1), multiple polyps (1), solitary
      polyps (9), and pseudopolyps (1). Ultrasound identified 11 polyps in 10 patients,
      missing two patients with small polyps less than 0.5 cm in diameter. The polyps
      were hyperechoic ovoid masses fixed to the colonic wall, with a stalk (7),
      submucosal infolding (5), and intraluminal floating (5). There was one false
      positive. Colonoscopy was refused by one patient and failed to reach beyond the
      distal sigmoid in another following previous surgery for malrotation. Colonoscopy
      was superior in identifying finer mucosal detail (colitis, ulcers, proctitis,
      anal fissure) and in detecting smaller polyps (sessile polyps, hyperplastic
      polyps). Hydrosonography of the colon is a simple, relatively non-invasive
      procedure that provides an alternative, radiation-free examination of the whole
      colon before colonoscopy. It is complementary to colonoscopy in the management of
      rectal bleeding in children.

PMID- 7639556
TI  - Faecal interleukin-8 and tumour necrosis factor-alpha concentrations in cystic
      fibrosis.
AB  - Interleukin-8 (IL-8) and tumour necrosis factor-alpha (TNF-alpha) concentrations
      were measured in faecal samples from nine patients with cystic fibrosis and nine
      healthy age matched controls. The patients were assessed with Shwachman score,
      apparent energy absorption, pancreatic enzyme dosage, simple spirometry, and
      presence of pseudomonal colonisation. Median (range) wet stool IL-8 and TNF-alpha
      concentrations in patients were 32,113 pg/g (21,656-178,128) and 3187 pg/g (368
      17,611) respectively, compared with < 43.5 pg (IL-8)/g (< 22-4079) and 99 pg (TNF
      alpha)/g (< 0.26-231) in controls. IL-8 concentration was negatively correlated
      with Shwachman score (r = -0.79) and pancreatic enzyme dosage (r = -0.77), but
      not with energy absorption. Seven patients were mature enough to cooperate with
      spirometry. Their IL-8 concentrations correlated with percentage predicted forced
      expiratory volume in one second (r = -0.78). IL-8 concentration was greater in
      four patients with, than five without, established pseudomonal colonisation:
      median difference 134,583 pg/g. TNF-alpha concentration was not correlated with
      measures of disease severity. Faecal IL-8 concentration might reflect the
      severity of pulmonary inflammation in cystic fibrosis and could provide an easily
      obtainable marker of disease activity.

PMID- 7639557
TI  - Behaviour in mucopolysaccharide disorders.
AB  - This paper reports a study of the nature and prevalence of behaviour problems in
      258 children with mucopolysaccharide disorders. Questionnaire data obtained
      through the post was supplemented by home visits to 42 families in the sample and
      by regular discussions with families at meetings of the Society for
      Mucopolysaccharide Diseases. High rates of behaviour problems were found,
      particularly in children with Sanfilippo's and Hunter's disease aged 5 to 9
      years. These included destructiveness, restlessness, and aggressiveness. Sleep
      problems were common across subtypes with an overall prevalence of 66%. Parents
      reported that they received little or no support in the management of these
      difficult behaviours. It is concluded that behaviour problems are a primary
      feature of the mucopolysaccharide disorders and place a major strain on families.
      Services to help families cope with these problems are urgently needed.

PMID- 7639558
TI  - Conditional reference charts to assess weight gain in British infants.
AB  - Growth monitoring in infancy is a useful tool for detecting growth disorders and
      failure to thrive. However, current weight charts do not monitor growth as such,
      they only identify infants whose weight centile is low and/or falling. A
      reference of conditional weight gain is described which compares an infant's
      current weight with that predicted from their previous weight, allowing for the
      fact that on average, light infants tend to grow faster than heavier infants. The
      reference, which expresses conditional weight gain as an SD score of centile, is
      based on the UK 1990 weight reference supplemented with correlation data on 223
      infants from the Cambridge Infant Growth Study measured regularly between 4 weeks
      and 2 years of age. The reference is validated with data on 727 infants from the
      Newcastle Regional Health Authority database. The conditional reference provides
      a valid assessment of the weight gain of British infants, over time periods of
      four or more weeks, throughout the first two years of life.

PMID- 7639559
TI  - Diagnosis and treatment of gastro-oesophageal reflux.

PMID- 7639560
TI  - Screening for growth: towards 2000.

PMID- 7639561
TI  - Body mass index centile charts to assess fatness of British children.

PMID- 7639562
TI  - Trends in breast feeding in New Zealand.

PMID- 7639563
TI  - Premenarchal endometrial shedding revealed by peritoneal dialysis.

PMID- 7639564
TI  - Management of anaphylactic reactions to food.

PMID- 7639565
TI  - Manganese in long-term paediatric parenteral nutrition.

PMID- 7639566
TI  - The irritable hip.

PMID- 7639567
TI  - [Is there a place for radical prostatectomy without lymphadenectomy?].
AB  - OBJECTIVES: Herein we present the procedure we have followed to determine N+ low
      risk factors which allow us to identify those patients with prostate cancer in
      whom radical perineal prostatectomy (RPP) can be performed without a previous
      staging lymphadenectomy, thereby maintaining the oncological principles but with
      less morbidity. METHODS: In a series of 88 patients who underwent RPP, we
      identified an N+ low-risk factor group; i.e., patients with clinically localized
      tumor of the prostate gland, a Gleason score of < or = 7 and PSA < or = 10 ng/ml.
      The foregoing criteria were based on the findings reported by Stamey and the
      status of the lymph nodes of our own series of radical prostatectomies. RESULTS:
      In 71 of the 88 patients with a follow up of more than one year, RPP was
      performed after laparoscopic pelvic lymphadenectomy. Of these 71 patients, 17
      (19.3%) presented the above-mentioned low-risk characteristics and were all pN-.
      Since then, the subsequent patients who met this low-risk criteria (n = 17; 19.3%
      of the total) were submitted to RPP alone without previous staging
      lymphadenectomy. The rate of positive margins in this group was 17.6%, all cases
      maintaining PSA within feminization levels after a mean follow-up of 21.7 months.
      Considering the overall series, 38.6% of the patients could have avoided
      lymphadenectomy according to our criteria. CONCLUSIONS: We have found RPP without
      previous staging lymphadenectomy to be a valid therapeutic option for patients
      with clinically localized prostate cancer, preoperative PSA < or = 10 ng/ml and a
      Gleason score of < or = 7. According to our data, this group accounts for
      approximately 40% of the patients in whom radical prostatectomy had been
      recommended.

PMID- 7639568
TI  - [Epidemiologic study of the factors influencing renal trauma in Cantabria].
AB  - OBJECTIVE: In this study, the most important factors that influence renal trauma
      (RT) were evaluated in patients that had suffered different types of accidents.
      METHODS: Data from 340 cases of RT that were seen over a period of 15 years were
      obtained. This was performed in two stages: first, data were obtained during this
      time period; secondly, the patients were followed after discharge from hospital.
      RESULTS: All this information was filed in a data base specifically for this
      purpose and were statistically analyzed to determine and quantify the types of RT
      and their incidence in relation to demographic and temporal factors, type of
      accident, etc. CONCLUSIONS: Weekends, alcohol, age, road traffic accidents, type
      of road, etc., are the most important factors that influence the development of
      RT. The incidence of RT in Cantabria is similar to that of the US and European
      countries.

PMID- 7639569
TI  - [Epidemiologic study of the clinical features, diagnosis, and treatment of kidney
      trauma in Cantabria].
AB  - OBJECTIVE: This study reviews the clinical features, methods and treatment of
      renal trauma (RT). METHODS: The epidemiological study was conducted using data
      from 340 cases of RT that had been treated in the Department of Urology of the
      Marques de Valdecilla University Hospital in Santander. All the information was
      filed in a data base specifically for the purpose. RESULTS: Statistical analyses
      of the data showed the incidence of the symptoms, diagnosis and treatment of RT.
      CONCLUSIONS: Radiological and ultrasound evaluation are still fundamental for the
      diagnosis of RT. Only 4% of these patients have died. Abdominal, thoracic and
      cranial injuries cause the most severe lesions. Concerning treatment, only 17% of
      the cases with RT required surgery.

PMID- 7639570
TI  - [Clinical trial with intravesical alfa-2b interferon for the prevention of T1
      transitional carcinoma of the bladder: preliminary results. Review of the
      bibliography].
AB  - OBJECTIVE: To assess the efficacy of 60 MU intravesical alpha-2b interferon (IFN)
      in preventing recurrence of transitional cell carcinoma of the bladder. METHODS:
      A prospective, randomized double-blind study was conducted to assess the efficacy
      of 60 MU intravesical alpha-2b IFN compared to a control group. T1G2-G3 and the
      G1 recurrent tumors were included in the study (30 in each group). Instillation
      was started 2-3 weeks after complete TUR and administered once weekly for 12
      weeks and once monthly thereafter for one year. RESULTS: The distribution
      according to sex and age of the patient, tumor size, grade and classification as
      primary or secondary was the same for both groups. Multiple tumors were prevalent
      in the IFN-treated group. During the first year of follow up, the tumor
      recurrence rate was 23.3% for the IFN-treated group and 36.6% for the control
      group. At 22.4 months mean follow up, the rate of recurrence was 40% for the IFN
      treated group and 46.6% for the control group. Of these recurrences, 8.3% of
      tumors in the IFN group showed progression in grade and/or stage versus 35.7% for
      the control group. The disease-free interval averaged 8.5 months; 10.5 for the
      treated group and 6.9 months for the control group. Local or systemic toxicity
      was negligible. CONCLUSIONS: Alpha-2b IFN is well-tolerated at a dose of 60 MU.
      It prolongs the disease-free interval and while throughout the follow up period
      the recurrence rate is similar to that of the control group, it does seem to
      markedly slow progression in the grade and/or stage of the tumor.

PMID- 7639571
TI  - [Incidence of the different types of hypercalciuria in Spain].
AB  - OBJECTIVE: To carry out a comparative biochemical study of primary
      hyperparathyroidism, the different types of hypercalciuria and a healthy
      population. METHODS: Fourteen patients with primary hyperparathyroidism and 103
      patients with idiopathic hypercalciuria were studied under conditions of
      restricted calcium intake and following a calcium load; the results were compared
      to those of 18 healthy controls. RESULTS: The patients with hyperparathyroidism
      showed high parathormone concentrations. Sixty-nine patients with idiopathic
      hypercalciuria had normal parathormone levels and were considered suffering from
      absorptive hypercalciuria. Those patients with high urinary calcium excretion
      under restricted calcium intake and normal urinary phosphate threshold were
      considered as being absorptive hypercalciuria type I, those with normal urinary
      calcium as absorptive hypercalciuria type II, and those with low urinary
      phosphate threshold constituted a renal phosphate leakage group. Thirty-four
      patients had normal serum calcium, elevated parathormone, hypophosphatemia and
      high calcium excretion under all dietary conditions, and were considered
      undergoing renal hypercalciuria. Patients with renal hypercalciuria had increased
      urine hydroxyproline and low serum calcium compared with the controls after an
      oral calcium load. This biochemical behaviour is compatible with secondary
      hyperparathyroidism caused by renal calcium leakage. CONCLUSIONS: In summary, the
      biochemical parameters: parathormone, urinary phosphate threshold and urinary
      calcium excretion, measured in fasting conditions, allowed classification of
      patients with idiopathic hypercalciuria.

PMID- 7639572
TI  - [Multivariate analysis of graft survival prognostic factors in renal
      transplantation].
AB  - OBJECTIVE: The aim of this paper is to identify the variables that could be of
      interest in the outcome of a series of cadaveric kidney transplantation performed
      at the University Hospital, Navarra School of Medicine, by means of
      multifactorial and multivariate statistical analyses. METHOD: We analyzed 307
      cadaveric kidney transplantation performed since 1976 at the University Hospital,
      School of Medicine, University of Navarra. Two series are included: the
      historical and the actual. The former did not include cyclosporine A in the
      immunosuppressor protocol. RESULTS: The first step was to compare survival in
      both series. The cyclosporine A series had a better survival, which was
      statistically significant (p < 0.0001). The prognostic factors in both series
      were also analyzed. The influence of the different variables were studied in the
      survival distribution. The worse prognostic variables of the historical group on
      allograft survival were donor's age (particularly between 20 and 50 years old),
      delayed graft function, serum creatinine level greater than 2.5 mg/dl at the
      first month following transplantation, general surgical complications, and
      vascular and other complications. In the actual group, the allografts with the
      worst survival were in those that received 4-10 pre-transplant blood
      transfusions, those with more that 2 HLA-DR mismatches, the hyperimmunized
      receptors with a level of pre-formed cytotoxic antibodies greater than 50%, those
      who rejected the allograft in the initial post-transplant period, those with a
      serum creatinine level greater than 2.5 mg/dl and those who presented surgical
      complications in general and urinary and vascular complications in particular.
      CONCLUSIONS: The multivariate analysis reveals that the prognostic factors of the
      historical group were delayed graft function, surgical complications, HLA A+B
      mismatches and the donor's age. In the actual group, the factors were receptor's
      age, surgical complications, large ischemia time, peak reactive antibody and
      number of rejections.

PMID- 7639573
TI  - [Endoscopic treatment of inguinal cryptorchism].
AB  - OBJECTIVE: A new endoscopic approach for the treatment of the testicle located in
      the inguinal canal is described. METHOD: Three trocars are inserted in the
      umbilicus and both flanks, then the spermatic vessels and vas deferens are
      dissected. A 2 cm skin incision is performed at the level of the internal
      inguinal ring and a finger is introduced. An incision is made endoscopically in
      the inguinal canal between the epigastric vessels and the conjoined tendon. With
      the finger the testicle is located and partially dissected. Pressure is applied
      on it until it is introduced into the peritoneal cavity through this incision,
      where it is released by dividing the sustentaculum testis. The cord is then
      pulled, the testicle is passed in front of the epigastric vessels and taken
      through the internal ring. Once the testicle is free in the peritoneum, it is
      brought into the scrotum. Finally, the inguinal canal is closed endoscopically.
      CONCLUSIONS: So far endoscopic orchiopexy has only been performed in
      intraabdominal testicles, and we believe that this procedure can extend the
      indications of endoscopic treatment for the undescended testis.

PMID- 7639574
TI  - [Physiology of erection].
AB  - OBJECTIVE: The present study reviews the mechanism involved in the initiation and
      maintenance of penile erection. METHOD: The study reviews the literature on the
      basic concepts supporting either "magically" or scientifically the erectile
      mechanism. An anatomo-physiological update is also included (i.e., the main
      neurological, muscular, and vasculoendothelial phenomena). RESULTS: Present
      studies based on the vasoactive action of different drugs have increased the
      knowledge on the neurological, muscular, and vasculoendothelial phenomena. The
      cavernous muscular relaxation may start and finish due to the equilibrium between
      the contractile adrenergic and the relaxing non adrenergic-non cholinergic
      stimulus through intracellular nitric oxide synthesis. This is an essential
      phenomenon involved in the entry and "trapping" of blood within the sinus spaces.
      CONCLUSIONS: Our knowledge on the erectile mechanisms through neuromediators is
      increasing. The role of the endothelium in intracellular nitric oxide synthesis
      and its relaxing effect, will improve our understanding of both physiological and
      therapeutic phenomena.

PMID- 7639575
TI  - [Analysis of the results with Rigiscan in 93 impotent patients].
AB  - OBJECTIVE: This study was undertaken to evaluate the performance of the Rigiscan
      in the diagnosis of sexual impotence. METHODS: Erectile nocturnal activity was
      evaluated by Rigiscan in 93 patients consulting for impotence; mean age 56.8
      years. Diagnosis and treatment were performed between October, 1990 and May,
      1992. Follow up is currently ongoing. RESULTS: 95.1% of the patients with normal
      recordings had no organic pathology, and 80% of these recordings were observed on
      the first night of the study. In ruling out organic pathology, the Rigiscan did
      not have a higher specificity than the report of early morning erection (EME) by
      the patients (p > 0.05). Seventy three percent of the pathological results on the
      Rigiscan studies were associated to organic pathology. This test showed a higher
      sensitivity than the absence of EME (p < 0.01). Although no pathognomonic
      diagnostic pattern was found, a flat pattern and uncoupling were highly
      suggestive of organic disorders. CONCLUSIONS: The Rigiscan is a useful diagnostic
      tool, especially in patients reporting no EME. Furthermore, the Rigiscan was able
      to detect almost all the patients with organic pathology.

PMID- 7639576
TI  - [Intraluminal invagination technic for the incision of ureterointestinal
      stenosis].
AB  - OBJECTIVE: This paper describes the endoscopic incision of uretero-ileal
      anastomotic strictures by a combined approach (percutaneous antegrade and
      endoscopic retrograde) using the intraluminal invagination technique over a
      balloon dilatation catheter. METHODS: The different steps of the surgical
      procedure of incision of the stenotic segment of different techniques of
      ureteroileal diversion (Bricker, Camey, ureterosigmoidostomy) are described in
      detail. Endoscopic images and those from the image intensifier are shown.
      RESULTS: Of the 6 cases described herein, incision was achieved in 5 and in 1
      case stenting of the stenotic segment could not be achieved. CONCLUSIONS:
      Intraluminal invagination of the stenotic segment considerably facilitates
      endoscopic incision.

PMID- 7639577
TI  - Between Scylla and Charybdis.

PMID- 7639578
TI  - Orthotopic liver transplantation in fulminant and subfulminant hepatitis. The
      Paul Brousse experience.
AB  - OBJECTIVE: The authors report on the experience of orthotopic liver
      transplantation in fulminant hepatitis at Paul Brousse Hospital. SUMMARY
      BACKGROUND DATA: Liver transplantation is a breakthrough in the treatment of
      patients with fulminant hepatitis. However, the indications, the timing for
      transplantation, the type of transplantation, and the use of ABO incompatible
      grafts in this setting still are debated. METHODS: Transplantation was indicated
      in patients with confusion or coma and factor V less than 20%, younger than 30
      years of age, and confusion or coma and factor V less than 30% older than 30
      years of age. RESULTS: Among 139 patients who met the aforementioned criteria for
      transplantation, 1 recovered, 22 died before transplantation, and 116 underwent
      transplants with a 1-year survival of 68%. Survival was 83% in patients with
      grade 1 and 2 comas at transplantation versus 56% (p < 0.001) in those with grade
      3 comas; it was 51% versus 81% (p < 0.001) in those transplanted with high risk
      (ABO-incompatible, split, or steatotic) and low-risk grafts, respectively. In a
      multivariate analysis, steatotic and partial grafts were predictive of poorer
      patient survival, and ABO incompatibility was predictive of poorer graft
      survival. CONCLUSIONS: Orthotopic liver transplantation is an effective treatment
      in fulminant hepatitis. Use of high-risk grafts permitted transplantation of 83%
      of patients, but was responsible for higher mortality.

PMID- 7639579
TI  - Ileal pouch-anal anastomoses complications and function in 1005 patients.
AB  - BACKGROUND: Restorative proctocolectomy and ileal pouch-anal anastomosis (IPAA)
      has become an established surgery for patients with chronic ulcerative colitis
      and familial adenomatous polyposis. PURPOSE: The authors report the results of an
      11-year experience of restorative proctocolectomy and IPAA at a tertiary referral
      center. METHODS: Chart review was performed for 1005 patients undergoing IPAA
      from 1983 through 1993. Preoperative histopathologic diagnoses were ulcerative
      colitis (n = 858), familial adenomatous polyposis (n = 62), indeterminate colitis
      (n = 75), and miscellaneous (n = 10). Information was obtained regarding patient
      demographics, type and duration of diseases, previous operations, and indications
      for surgery. Data were collected on surgical procedure and postoperative
      pathologic diagnosis. Early (within 30 days after surgery) and late complications
      were noted. Follow-up included an annual function and quality-of-life
      questionnaire, physical examination, and biopsies of the pouch and anal
      transitional zone. RESULTS: Of the 1005 patients (455 women), postoperative
      histopathologic diagnoses were as follows: ulcerative colitis (n = 812), familial
      adenomatous polyposis (n = 62), indeterminate colitis (n = 54), Crohn's disease
      (n = 67), and miscellaneous (n = 10). During a mean follow-up time of 35 months
      (range 1-125 months), histopathologic diagnoses were changed for 25 patients. The
      overall mortality rate was 1% (n = 10 patients, early = 4, late = 6); one death
      (0.1%) was related to pouch necrosis and sepsis. The overall morbidity rate was
      62.7% (1218 complications in 630 patients; early, n = 27.5%; late, n = 50.5%).
      Septic complication and reoperation rates were 6.8% and 24%, respectively. The
      ileal pouch was removed in 34 patients (3.4%), and it is nonfunctional in 11
      (1%). Functional results and quality of life were good to excellent in 93% of the
      patients with complete data (n = 645) and are similar for patients with
      ulcerative colitis, familial adenomatous polyposis, indeterminate colitis, and
      Crohn's disease. Patients who underwent operations from 1983 through 1988 have
      similar functional results and quality of life compared with patients who
      underwent operations after 1988. CONCLUSION: Restorative proctocolectomy with an
      IPAA is a safe procedure, with low mortality and major morbidity rates. Although
      total morbidity rate is appreciable, functional results generally are good and
      patient satisfaction is high.

PMID- 7639580
TI  - Choledochal cyst in the adult.
AB  - OBJECTIVE: The authors examined the natural history of choledochal cysts in
      adults treated surgically. BACKGROUND: An initial diagnosis of choledochal cyst
      is uncommon in adults. The recommended treatment is excision, rather than bypass,
      to achieve effective biliary drainage and because of the risk of cancer. METHODS:
      A retrospective study of 27 adult patients was completed to determine the
      frequency of anastomotic complications and the incidence of cancer. RESULTS:
      Fifteen patients were treated by cyst excision, and one developed an anastomotic
      stricture, treated by percutaneous dilation. Eight of 11 patients treated by cyst
      enterostomy required additional surgery for anastomotic revision. A final patient
      was treated by T-tube drainage. Five of the seven patients with cancer have died
      at a mean of 21.6 months. CONCLUSION: This experience documents the high
      incidence of cancer (26%), and high rate of stricture after cyst enterostomy
      (73%). The dismal prognosis once cancer has developed warrants cyst excision,
      even in asymptomatic patients, including those with prior cyst enterostomies.

PMID- 7639581
TI  - A rational process for the reform of the physician payment system.
AB  - Analysis of the resource-based relative value scale (RBRVS) for physician payment
      indicates that in 1996, hourly reimbursement rates will be unrelated to the
      intensity of work and income will be unrelated to hours worked. A "consensus
      method" of payment is proposed as an alternative to the RBRVS. METHOD: As with
      the method of the RBRVS study, a pilot survey asked a specialty-representative
      cohort of physicians to assign dimensionless numbers to the relative value of
      work in 15 specialties using the Hsiao et al. definition of work intensity as
      "time modified by, a) mental effort, b) clinical judgment, c) technical skill,
      and d) physical effort under stress." The consensus method is similar to that of
      the Hsaio method, except there is no mathematical transformation of the raw data
      to establish specialty work values once the data are collected. A comparative
      analysis was then made of work hours, reimbursement rates, and annual income with
      1) the customary prevailing and reasonable system (CPR, pre-1992), 2) the RBRVS
      system (1996), and 3) the proposed consensus system. RESULTS: The RBRVS intends
      that physicians be reimbursed on the basis of time and intensity of work. Neither
      the CPR nor the RBRVS systems accomplish this objective when the data and
      computational methods of the Physician Payment Review Commission are used with
      independently determined work intensity to compute hourly reimbursement rates in
      the specialties. The consensus method shows the desired direct linear correlation
      of income with both length of the physician's work week and intensity of effort.
      It rates the primary care specialties as a group more highly than the RBRVS.
      CONCLUSION: The proposed consensus method meets the original intent of the RBRVS
      to reimburse physicians on the basis of the resource input of time as modified by
      the criteria of Hsiao et al.

PMID- 7639582
TI  - Exogenous transforming growth factor-beta amplifies its own expression and
      induces scar formation in a model of human fetal skin repair.
AB  - OBJECTIVE: Fetal skin wounds heal without scarring. To determine the role of TGF
      beta 1 in fetal wound healing, mRNA expression of TGF-beta 1 was analyzed in
      human fetal and adult skin wounds. METHODS: Human fetal skin transplanted to a
      subcutaneous location on an adult athymic mouse that was subsequently wounded
      heals without scar, whereas human adult skin heals with scar formation in that
      location. In situ hybridization for TGF-beta 1 mRNA expression and species
      specific immunohistochemistry for fibroblasts, macrophages, and neutrophils were
      performed in human adult wounds, fetal wounds, and fetal wounds treated with a
      TGF-beta 1 slow release disk. RESULTS: Transforming growth factor-beta 1 mRNA
      expression was induced by wounding adult skin. No TGF-beta 1 mRNA upregulation
      was detected in human fetal skin after wounding. However, when exogenous TGF-beta
      1 was added to human fetal skin, induction of TGF-beta 1 mRNA expression in human
      fetal fibroblasts occurred, an adult-like inflammatory response was detected, and
      the skin healed with scar formation. CONCLUSIONS: Transforming growth factor-beta
      1 is an important modulator in scar formation. Anti-TGF-beta 1 strategies may
      promote scarless healing in adult wounds.

PMID- 7639583
TI  - Transforming growth factor-beta receptors and mannose 6-phosphate/insulin-like
      growth factor-II receptor expression in human hepatocellular carcinoma.
AB  - OBJECTIVE: The authors examined the expression of transforming growth factor-beta
      receptor (TGF-beta r) types I and II and the mannose 6-phosphate/insulin-like
      growth factor-II receptor (M6-P/IGF-IIr) in human hepatocellular carcinoma (HCC).
      SUMMARY BACKGROUND DATA: Transforming growth factor-beta (TGF-beta) is part of a
      superfamily of peptide-signaling molecules that play an important role in
      modulating cell growth. It is secreted as a latent complex and therefore, must be
      activated to elicit a biological response. Bioactivation of the TGF-beta complex
      is facilitated by binding to the M6-P/IGF-IIr. Once activated, TGF-beta exerts
      its effects by binding to specific cell membrane TGF-beta receptors. The loss of
      responsiveness of hepatocytes to TGF-beta has been implicated in
      hepatocarcinogenesis and could result from a loss in the expression of either the
      TGF-beta receptors or the M6-P/IGF-IIr. METHODS: Human hepatocellular carcinomas
      and surrounding normal tissue were collected from operating room samples and snap
      frozen in liquid nitrogen (n = 13). Tissues from two tumors were fixed in Omni
      fix for sectioning and immunohistochemistry staining for the M6-P/IGF-IIr and TGF
      beta 1. RNA was extracted from both normal and malignant liver tissue and
      analyzed using an RNase protection assay. SDS-PAGE of purified membrane
      hybridized with 125I-TGF-beta 1 and 125I-IGF-II was used to determine the TGF
      beta type I (TGF-betarI) and type II (TGF-beta rII) receptors and M6-P/IGF-IIr
      protein levels, respectively. Gels were quantitated by phosphorimager, and a
      paired t test was used for statistical analysis. RESULTS: In HCC, a 60% (p <
      0.01) and 49% (p < 0.02) reduction in the mRNA levels for T beta rI and T beta
      rII, respectively, relative to the receptor levels in surrounding normal liver,
      was shown. A similar decrease in the receptor protein levels also was observed.
      The M6-P/IGF-IIr mRNA and protein levels were reduced in 7 of 11 hepatocellular
      carcinomas. Immunohistochemical staining demonstrated an absence of intracellular
      TGF-beta 1 and reduced M6-P/IGF-IIr in the hepatocellular carcinoma cells.
      CONCLUSIONS: These results demonstrate that human HCCs have a significantly
      reduced expression of both the TGF-beta rI- and TGF-beta rII-signaling receptors
      for TGF-beta. This may provide a selective growth advantage to the HCC by
      allowing them to escape the mito-inhibitory effects of activated TGF-beta.
      Furthermore, in the subset of HCC in which the expression of the M6-P/IGF-IIr is
      downregulated, the bioactivation of TGF-beta also may be impaired.

PMID- 7639584
TI  - Pathogenesis and prevention of early pancreatic infection in experimental acute
      necrotizing pancreatitis.
AB  - OBJECTIVE: The authors test antibiotic strategies aimed at either mitigating
      bacterial translocation from the gut or delivering antibiotics specifically
      concentrated by the pancreas for prevention of early secondary infection after
      acute necrotizing pancreatitis. BACKGROUND: Infection currently is the principal
      cause of death after severe pancreatitis. The authors have shown that the risk of
      bacterial infection correlates directly with the degree of tissue injury in a
      rodent model of pancreatitis. Bacteria most likely arrive by translocation from
      the colon. METHODS: Severe acute necrotizing pancreatitis was induced in rats by
      a combination of low-dose controlled intraductal infusion of glycodeoxycholic
      acid superimposed on intravenous cerulein hyperstimulation. At 6 hours, animals
      were randomly allocated to five treatment groups: controls, selective gut
      decontamination (oral antibiotics and cefotaxime), oral antibiotics alone,
      cefotaxime alone, or imipenem. At 96 hours, surviving animals were killed for
      quantitative bacterial study of the cecum, pancreas, and kidney. RESULTS: The 96
      hour mortality (35%) was unaffected by any treatment regimen. Cecal gram-negative
      bacteria were significantly reduced only by the oral antibiotics. Pancreatic
      infection was significantly reduced by full-gut decontamination and by imipenem,
      but not by oral antibiotics or by cefotaxime alone. Renal infection was reduced
      by both intravenous antibiotics. CONCLUSIONS: Early pancreatic infection after
      acute necrotizing pancreatitis can be reduced with a full-gut decontamination
      regimen or with an antibiotic concentrated by the pancreas (imipenem) but not by
      unconcentrated antibiotics of similar spectrum (cefotaxime) or by oral
      antibiotics alone. These findings suggest that 1) both direct bacterial
      translocation from the gut and hematogenous seeding interplay in pancreatic
      infection while hematogenous seeding is dominant at extrapancreatic sites and 2)
      imipenem may be useful in clinical pancreatitis.

PMID- 7639585
TI  - Nitric oxide regulates basal but not capsaicin-, CGRP-, or bile salt-stimulated
      rabbit esophageal mucosal blood flow.
AB  - BACKGROUND/AIMS: Esophageal mucosal blood flow is a dynamic phenomenon that is
      altered by luminal content that probably represents an important intrinsic method
      of defense. This study investigated the role played by endogenous nitric oxide in
      the regulation of esophageal mucosal blood flow at rest and in response to
      luminal capsaicin, a specific stimulant for visceral afferent nerves, as well as
      calcitonin gene-related peptide, and the bile salt deoxycholate. METHODS: The L
      arginine analog L-NAME was used to block nitric oxide synthesis. Radiolabeled
      microspheres were used to measure blood flow in a well-characterized rabbit
      model. Phenylephrine was used to mimic the hemodynamic effects of L-NAME to show
      the specificity of positive findings. RESULTS: Administration of L-NAME led to a
      significant reduction in mucosal blood flow at rest, an effect that was not
      shared by phenylephrine. The blood flow responses to luminal capsaicin, intra
      arterial calcitonin gene-related peptide (CGRP), and luminal deoxycholate,
      however, were not diminished in the presence of L-NAME. CONCLUSIONS: Although
      nitric oxide may play a role in the maintenance of normal resting esophageal
      mucosal blood flow, the reactive responses to luminal capsaicin, luminal
      deoxycholate, and intra-arterial CGRP are not nitric oxide dependent.

PMID- 7639587
TI  - Presence of antiphospholipid antibodies and thromboses.

PMID- 7639586
TI  - Noncardiac surgery in long-term implantable left ventricular assist-device
      recipients.
AB  - OBJECTIVE: The authors describe their experience with left ventricular assist
      device (LVAD) recipients undergoing noncardiac surgery and delineate surgical,
      anesthetic, and logistic factors important in the successful intraoperative
      management of these patients. SUMMARY BACKGROUND DATA: Left ventricular assist
      devices have become part of the armamentarium in the treatment of end-stage heart
      failure. As the numbers of patients chronically supported with long-term
      implantable devices grows, general surgical problems that are commonly seen in
      other hospitalized patients are becoming manifest. Of particular interest is the
      intraoperative management of patients undergoing elective noncardiac surgical
      procedures. METHODS: The anesthesia records and clinical charts were reviewed for
      eight ventricular assist-device recipients undergoing general surgical procedures
      between August 1, 1990 and August 31, 1994. RESULTS: A total of 12 procedures
      were performed in 6 men and 2 women averaging 52.7 years of age. Mean time
      elapsed from device implantation to operation was 68 +/- 35 days. Conventional
      inhalational and intravenous anesthetic techniques were well tolerated in these
      patients undergoing diverse surgical procedures. No perioperative mortality was
      observed. Five of eight patients went on to successful cardiac transplantation.
      CONCLUSIONS: Hemodynamic recovery after LVAD insertion has defined a new group of
      patients who develop noncardiac surgical problems often seen in other critically
      ill patients. Recognition of the unique potential problems that the LVAD
      recipient may encounter in the perioperative period--in particular patient
      positioning, device limitations, and fluid and inotropic management--will ensure
      an optimal surgical outcome for LVAD recipients undergoing noncardiac surgery.

PMID- 7639588
TI  - Cost and outcome of the Whipple procedure.

PMID- 7639589
TI  - Laparoscopic alternatives for the repair of inguinal hernias.

PMID- 7639590
TI  - Laparoscopic alternatives for the repair of inguinal hernias.

PMID- 7639591
TI  - Laparoscopic alternatives for the repair of inguinal hernias.

PMID- 7639592
TI  - [A comparison of the effects of serotonin, 2-(2-aminoethyl)quinoline (D-1997) and
      sumatriptan on the external carotid blood flow in the dog].
AB  - The quinoline derivative, 2-(2-aminoethyl)-quinoline (D-1997) has been shown to
      mimic the contractile effects induced by serotonin (5-hydroxytryptamine; 5-HT) in
      the saphenous vein and basilar artery of the dog. Inasmuch as the receptor
      mechanisms mediating the above effects are similar to those involved in 5-HT
      induced vasoconstriction of the canine common carotid circulation, the present
      study was set out to analyze the haemodynamic profile of D-1997 in the canine
      external carotid vascular bed. The effects of D-1997 were compared with those
      produced by 5-HT and the antimigraine drug, sumatriptan. One-min intracarotid
      (i.c.) infusions of D-1997 (10, 30, 100, 300 and 1000 micrograms/min), 5-HT (0.3,
      1, 3, 10, 30 and 100 micrograms/min) and sumatriptan (3, 10, 30 and 100
      micrograms/min) elicited dose-dependent decreases in external carotid blood flow
      (ECBF); since the infusions of agonists did not modify arterial blood pressure,
      they produced dose-dependent increases in external carotid resistance (ECR). The
      vasoconstrictor responses to D-1997 and 5-HT were of short duration (up to 10
      min) whilst those to sumatriptan were longer lasting (up to 40 min). In addition,
      the effects induced by the agonists in the external carotid bed did not affect
      basal resistance in the contralateral common carotid, thereby suggesting a local
      effect by D-1997. The rank order of agonist potency was 5-HT > sumatriptan > D
      1997; however, the order of agonist efficacy, represented as the maximum response
      obtained with the highest dose, displayed a different pattern, namely, D-1997 >
      or = sumatriptan > 5-HT.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7639593
TI  - [A new electrocardiographic algorithm for localizing accessory pathways using
      only the polarity of the QRS complex].
AB  - From 250 consecutive patients who underwent radiofrequency ablation of accessory
      pathways, we studied 102 patients with successful ablation of a single overt
      accessory pathway. All patients had manifested preexcitation on a baseline 12
      lead electrocardiogram. None of this patients had additional congenital or
      acquired cardiac abnormalities which could have affected the QRS morphology. A
      new algorithm for localizing the AP site was developed, based only on the
      polarity of the QRS complexes in DIII, V1 and V2, without analysis of the delta
      wave. We could localize the accessory pathway in five sites with 88% of
      probability of success. This simplify the electrocardiographic analysis of Wolff
      Parkinson White and improvement the results of radiofrequency ablation.

PMID- 7639594
TI  - [Structural and functional changes in the heart of the hypertensive patient. An
      echocardiographic study].
AB  - We studied 15 patients with essential hypertension (EH) in whom the diagnosis was
      corroborated with ambulatory blood pressure monitoring (ABPM). The blood pressure
      levels (BP) were compared with values obtained from healthy people (HP). We
      studied 31 HP with 2-D echocardiogram and the parameters of ventricular
      performance were compared with the values obtained from EH people. ABPM shown
      that the EH people has higher BP values than HP around 24 hs (EH loss the
      circadian rhythm of BP). On the other hand the EH had left ventricular
      hypertrophy (LVH) with normal systolic ventricular function (VF). The systolic
      wall stress was low because the LVH was inappropriate. The LVH as adaptative
      mechanism maintains normal the VF in spite of pressure overload without
      increasing MVO2. When the pressure overload is not eradicated in a variable
      amount of time the adaptative mechanisms slowly change to a pathologic process
      caused by collagen deposition in the interstitium of the heart. In advanced
      stages the remodeling process causes diastolic disfunction, myocardial ischemia,
      arrhythmias and death by heart failure or suddenly. This last stage is the real
      hypertensive heart disease.

PMID- 7639596
TI  - [Valve prostheses and transesophageal echocardiography].
AB  - The aim of this paper is to inform about the experience of the Echocardiography
      Department of the National Institute of Cardiology Ignacio Chavez, in the
      assessment of prosthetic valves dysfunction by transesophageal echocardiography.
      Sixty patients with a total of 75 prosthetic valves: 19 bioprostheses and 56
      mechanical valves were studied. Forty four were in mitral position, 27 in aortic
      position and 4 in tricuspid position. All patients were evaluated using 5 MHz
      monoplane or biplane transesophageal transducers. The 52% (39) of the studied
      prosthetic valves were found normally functioning. However, 48% (36) of these
      showed signs of dysfunction. The causes of dysfunction in the mechanical valves
      were: obstruction, pannus, infectious endocarditis and periprosthetic leak, and
      in relation with bioprostheses rupture of the leaflets, stenosis and
      calcification, partial dehiscence, infectious endocarditis and periprosthetic
      leak were identified. The obtained percentage and type of prosthetic valves
      dysfunction in our results agree with those reported in the literature and
      confirm the great utility of transesophageal research in the detection of the
      valvular prosthetic dysfunction.

PMID- 7639595
TI  - [Mitral insufficiency after mitral balloon-catheter valvuloplasty: its incidence,
      predictive factors and prognosis].
AB  - From October 1991 to October 1993, a total of 205 patients with rheumatic mitral
      stenosis (178 female, 27 male, mean age 38 years, range 17-72) underwent
      percutaneous transvenous mitral commissurotomy (PTMC), 138 with the Inoue balloon
      and 67 with double balloon-catheter techniques. Mitral regurgitation (MR) was
      detected in 10% of the cases prior to the procedure, and 37% after PTMC (p <
      0.05), grade I in 45 patients (22%), grade II in 24 (12%), grade III in 4 (2%),
      and grade IV in 3 (1.5%) cases (p = 0.003, 0.002, N.S. and N.S., respectively. In
      40% of the total group (83/205) there was no new or worsening MR; in 26.8% of the
      cases (55/205) new MR appeared (p = 0.004); in 23% (47/205) MR increased one
      grade (p = 0.002) and in 9.7% (20/205) two or more grades. The comparative
      incidence of MR was 40.5% (56/138) with the Inoue balloon, and 16.4% (11/67) with
      the double balloon technique (p = 0.03); the severity of MR was grade I in 27% vs
      9% (p = 0.001), grade II in 9.4% vs 6% (p = 0.05), grade III in 2.1% vs 1.5%
      (N.S.), and grade IV in 2.1% vs 0% (N.S.). Only the presence of commissural
      calcification and echo-score > 8 points were found as independent predictors of
      severe MR. In conclusion, mild and moderate MR occur frequently after PTMC, with
      significantly greater incidence using the Inoue technique. Severe MR following
      PTMC is much less frequent, and the comparative incidence is somewhat greater
      with the Inoue balloon, though the difference is not significant.

PMID- 7639597
TI  - [Corrected transposition of the great arteries in patients over 65].
AB  - Three cases with corrected transposition of the great arteries in patients older
      than 65 years are described. Two had atrial situs solitus and one atrial situs
      inversus. One had pulmonary valvular stenosis with valvular calcification and a
      small ventricular septal defect in association with ischemic heart disease. This
      patient died due to cardiac failure at the age of 80 years. The second case was
      associated with ventricular septal defect, atrial septal defect and pulmonary
      hypertension. The third patient presented with mild tricuspid regurgitation.
      Although this congenital heart malformation is theoretically compatible with
      normal life, few patients have long survival because of associated congenital
      defects or the subsequent development of tricuspid regurgitation or
      atrioventricular block.

PMID- 7639598
TI  - [Acute infarct of the right ventricle secondary to a massive pulmonary
      thromboembolism].
AB  - The hemodynamic and cardiovascular responses to a massive pulmonary embolism are:
      severe pulmonary hypertension, right ventricular failure and cardiogenic shock.
      The irreversible state of the latest condition and mortality could be due to a
      secondary right ventricle myocardial infarction, an entity which was first
      described in 1949. We report a necropsy case with massive pulmonary embolism and
      as a relevant finding a recent right ventricular myocardial infarction without
      significant obstructive coronary lesions. The relevance of right ventricle
      myocardial infarction as a major risk factor for mortality, its clinical and
      hemodynamic profile as well as the ischemic phenomena, are analyzed. It is
      emphasized also the importance of an early lysis of thrombus to rescue myocardium
      and to preserve right ventricle viability. This could be the first case reported
      in Mexico, in which the relationship between massive pulmonary embolism and right
      ventricle myocardial infarction is demonstrated as a determinant factor for
      mortality.

PMID- 7639599
TI  - [The methodology of teaching cardiology via images].

PMID- 7639600
TI  - [Kawasaki disease: the echocardiographic diagnosis of coronary aneurysms. A
      report of 2 cases].
AB  - We report two infants with Kawasaki disease and coronary aneurysms diagnosed by
      echocardiography. First case, a one year old male with abnormalities of left
      coronary artery, developed a myocardial infarction and died three weeks later.
      Second case a two months old male with aneurysm in the right coronary artery who
      doing well three months after the diagnosis was made. Echocardiography is the
      primary tool for evaluation and follow up of coronary abnormalities.

PMID- 7639601
TI  - [The cellular substrates of the acute myocardial infarct syndrome].

PMID- 7639602
TI  - [Interactions between the renin-angiotensin-aldosterone system and sympathetic
      neurotransmission].

PMID- 7639603
TI  - [60th anniversary of the Mexican Society of Cardiology].

PMID- 7639604
TI  - [Effects of adenosine on automaticity and post-potential oscillations in Purkinje
      fibers of mammals].
AB  - The aim of the present paper was to study the effects of adenosine (ADO) on
      automaticity and after potential oscillations on canine cardiac Purkinje fibers.
      ADO concentrations from 10(-8) to 10(-5) M were used. The intracellular
      electrical activity was recorded with conventional microelectrodes. ADO increased
      during the first two minutes the basic cycle length (BLC) with concentrations
      higher than 10(-8) M, to a value 50% above control, later there is a progression
      to a steady state. The dose-response curve in the steady state is sigmoidal and
      resembles those of receptor occupation. The slopes of pacemaker potentials have a
      tendency to decrease along with the increase in BLC length. After potential
      oscillations decrease with 10(-8) M of ADO but not with larger concentrations.
      There results supports the hypothesis that ADO produces an increase in the time
      independent potassium current similar to the one described for atrial and
      ventricular myocytes. This effect probably depends on specific receptor
      stimulation. The biphasic time course suggests the existence of subtypes of A1
      receptor with different dissociation constants and affinities but with similar
      actions. The idea that the ADO effects depend mainly on the potassium currents
      and not on I(f) is supported by the absence of a dose-dependent effects in the
      oscillatory after potentials.

PMID- 7639605
TI  - [Antibodies against extracellular products of group A Streptococcus. Diagnostic
      importance in acute rheumatic fever].
AB  - Streptococcal throat infection is a sine qua non for the development of rheumatic
      fever (RF) in genetically susceptible people. Demonstration of such infection is
      not easy. In overt RF less than 10% of patients still carry streptococci in their
      throat and immunologic methods are required to identify antibodies against
      streptococcal products (SP). Humoral response against SP was studied in children
      and adults with and without RF. Antistreptolysin O (ASO) showed a non-gaussian
      distribution, and reference value was established as percentile. Adults have a 97
      percentile of 227, in children 90 percentile was 451. When RF was present all
      cases, except one, showed higher values. When antibodies against SP besides ASO
      were sought by an agglutination test (Streptozyme tm), people below 15 years of
      age showed low titers in 15 out of 28 cases. In contrast, high titers were the
      rule in children suffering RF. High ASO titer correlated with high Streptozyme
      value. These methods are capable to recognize an specific immune response against
      Group A Beta hemolytic streptococci, and are valuable tools in the diagnosis of
      RF.

PMID- 7639606
TI  - [The DDD pacemaker implanted intravenously].
AB  - Retrospectively, we studied 66 consecutive patients in whom we implanted an
      intravenous DDD pacemaker. The indications were: AV block in 52 patients (79%),
      sick sinus syndrome in 5 patients (7.5%), both AV block and sick sinus syndrome
      in 4 patients (6%), and other causes in 5 (7.5%). The venous access route was by
      subclavian punction in 38 cases (57.5%) and by cephalic vein dissection in 28
      (42.5%). With a mean follow-up of 16 months, there were complications in 11
      patients (17%), in 9 of them, it was necessary a change in pacing mode different
      to DDD, and was possible to maintain a DDD pacing mode in 2 patients with a
      minimal reprogramming. The complications were: A) lost of sense and/or atrial
      capture in 10 patients (3 of them, had also loss of ventricular capture, one had
      pacemaker-mediated tachycardia, other had diaphragmatic stimulation and other had
      a severe infection of the pocket), B) atrial fibrillation appeared in another
      patient. At the implantation time there were significant differences between
      patients with and without complications on follow-up, the P wave amplitude was
      1.86 +/- 0.75 mV in the first group vs. 3.06 +/- 1.52 mV in the latter group, p <
      0.005, and the atrial pacing threshold was 1.10 +/- 1.17 microJ in the first
      group vs. 0.65 +/- 0.66 microJ in the latter group, p < 0.005. We consider that
      dual chamber stimulation is a well established form of therapy, although, it
      requires a more laborious implantation and specialized personal for its follow
      up.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7639608
TI  - [Long-term follow up of Doppler parameters of ventricular diastolic function
      after myocardial infarct].
AB  - Forty-two survivors of a first transmural, noncomplicated myocardial infarction
      underwent mitral flow pulsed-Doppler studies both at predischarge time and 1 year
      later, in order to assess the long-term evolution of diastolic parameters in the
      absence of reinfarction or revascularization procedures. Results showed a
      decrease of mean value of E wave peak velocity (59.6 +/- 14 cm/sec vs 46.8 +/- 13
      cm/sec, p < 0.001). Mean value of A wave peak velocity remained stable (59.4 +/-
      16 cm/sec vs 58.8 +/- 13 cm/sec, p = 0.86). The mean value of the E/A ratio
      showed a significant decrease during follow-up from an initial value > or = 1 to
      a final value < 1 (1.08 +/- 0.4 vs 0.82 +/- 0.2, p < 0.01). From the point of
      view of individual results, only 8 of 22 patients with an E/A ratio > or = 1
      before discharge presented the same ratio value 1 year later, whereas only 1
      patient with a E/A ratio < 1 before discharge presented a > 1 value of this ratio
      in the late study. It is concluded that during the first year of evolution after
      transmural, nonrevascularized, noncomplicated infarction, the left ventricle
      filling pattern displays a significant change from predischarge phase (mainly
      protodiastolic with predominant E wave) to late follow-up (mainly telediastolic
      with predominant A wave). Different hypotheses to explain these results are
      discussed.

PMID- 7639607
TI  - [Residual shunts after application of the Rushkind occlusion system in closure of
      persistent ductus arteriosus. Insertion of a second device].
AB  - From May 1991 to August 1994, we performed transcatheter closure of patent ductus
      arteriosus with Rashkind umbrella system in 25 patients. In one, the device had
      embolism, to the right pulmonary artery and was operated 24 hs afterwards without
      complications. Seven had residual shunts, two had subsequent surgery, two are
      being followed (one for mild and one for moderate residual shunt). In the other
      three cases we inserted a second device. We used a 12 mm device in two cases and
      a 17 mm device in the other. Two cases had total occlusion 24 hrs after and in
      one had mild residual shunt without clinical repercussion. There were no
      complications. All had electrocardiographic and clinical improvement, take no
      medication, and their cardiomegaly had decreased (Cardiac index pre 61 vs post
      54%). In conclusion the insertion of a second device is safe and effective
      alternative for residual shunt after first Rashkind occluder.

PMID- 7639609
TI  - [Adenosine for suppression of paroxysmal supraventricular tachycardia in a
      newborn infant. First case in Mexico].
AB  - We present the case of a 20-day old baby who was admitted with orthodromic
      supraventricular reentry tachycardia with a heart-rate of 300/minute. Suppression
      of the arrhythmia was tried with vagal maneuvers and digoxin. On failure to
      control the heart rate, a 0.05 mg/kg intravenous bolus of adenosine was given,
      with immediate response and subsequent normal heart rate and rhythm. In the
      following year he has been adequately controlled with oral digoxin. This is the
      first pediatric patient treated with adenosine in Mexico. Even though experience
      elsewhere in this age group is also limited, the properties of adenosine make it
      a valuable first-choice drug for the control of paroxysmal supraventricular
      tachycardia.

PMID- 7639610
TI  - [The family of a child with congenital heart disease].

PMID- 7639611
TI  - [Cardiology in medical botany of New Spain].

PMID- 7639612
TI  - Bioassay and pharmacological characterization of the nitrergic neurotransmitter.
AB  - Based on organ bath experiments illustrating nitric oxide (NO) or an NO-releasing
      substance as mediator of the nonadrenergic noncholinergic (NANC) nerve-induced
      relaxations in the canine ileocolonic junction and rat gastric fundus, a bioassay
      superfusion technique was developed to detect and characterize the inhibitory
      NANC neurotransmitter. Evidence is provided that NANC nerve stimulation results
      in the release of a vasorelaxant factor with pharmacological properties similar
      to NO: its release is blocked by inhibition of the NO biosynthesis and
      tetrodotoxin, but enhanced by L-arginine. Its half-life is comparable to that of
      NO, and its biological activity is enhanced by superoxide dismutase, but
      abolished by hemoglobin. In addition, the nitrergic transferable factor is
      similarly affected as authentic NO by pyrogallol, hydroquione, hydroxocobalamin
      and L-cysteine. Nitrosothiols, like S-nitroso-L-cysteine, S-nitrosoglutathione
      and S-nitroso-N-acetyl-D,L- penicillamine, on the other hand, have a different
      pharmacological profile compared to NO and the nitrergic factor, indicating that
      NO, and not a nitrosothiol, is released from inhibitory NANC nerves in the canine
      ileocolonic junction. This nerve-induced release is Ca(2+)-dependent and
      prejunctionally regulated by K+ channels and alpha 2-adrenoceptors: blockade of
      K+ channels enhances the release, whereas alpha 2-adrenoceptor activation reduces
      the release of the nitrergic factor, possibly by activating K+ channels.

PMID- 7639613
TI  - The 5-hydroxytryptamine-nitric oxide connection: the key link in the initiation
      of migraine?
AB  - The evidence for an involvement of 5-hydroxytryptamine (5-HT) and nitric oxide
      (NO) in the initiation of migraine is reviewed. Based on this, the following
      scenario is proposed. Endogenous 5-HT, arising perhaps from platelets but more
      likely from perivascular 5-HT-containing neurons in response to different types
      of "stress", would activate 5-HT2B/5-HT2C receptors on endothelial cells of the
      cerebral vasculature to release NO. Nitric oxide would, by directly activating
      sensory neurons, induce neurotransmitter release, plasma extravasation, pain and
      hyperalgesia. The result would be induction of the "sterile" inflammatory
      response, believed to be the key step in the development of migraine.

PMID- 7639614
TI  - Interactions of serotonin with multiple receptors and neurotransmitters in the
      guinea-pig isolated colon.
AB  - The motor effects of 5-hydroxytryptamine (5-HT; serotonin) on the guinea-pig
      isolated proximal colon were studied and analyzed. A classical organ bath setup
      was used to measure the longitudinal muscle responses isotonically. 5
      Hydroxytryptamine induced concentration-dependent contractions which were
      preceded by relaxations at low concentrations. By means of the neurotoxin,
      tetrodotoxin, the muscarinic cholinoceptor antagonist, atropine, and selective 5
      HT receptor antagonists, it was shown that the contractions to 5-HT are mediated
      by 5-HT2A receptors, localized on the smooth muscle, and by 5-HT3 and 5-HT4
      receptors, localized on cholinergic nerves. The relaxation was abolished by
      tetrodotoxin and appeared to be mediated by two 5-HT receptor subtypes; the
      pharmacological profile of the high affinity 5-HT receptor resembled that of 5
      HT2C receptors though it displayed also pronounced differences. Subsequently, it
      was shown that nitric oxide is the mediator released by lower concentrations of 5
      HT, while, at higher concentrations, adenosine triphosphate could be involved as
      an end neurotransmitter as well. No evidence for a peptidergic neurotransmitter,
      such as vasoactive intestinal polypeptide, was obtained. Results with two 5-HT
      analogues confirmed the presence of a dual 5-HT receptor system (high and low
      affinity) regulating each the release of a different neurotransmitter (nitric
      oxide and adenosine triphosphate, respectively). The above described results
      stress the important role of 5-HT as a neurotransmitter involved in
      gastrointestinal motility.

PMID- 7639615
TI  - Adenosine receptors: protein and gene structure.
AB  - Adenosine produces a wide variety of effects throughout the body via activation
      of cell surface adenosine receptors. Adenosine receptors belong to the family of
      seven transmembrane domain G protein-coupled receptors and four subtypes have
      been cloned from a variety of species: the A1AR, A2aAR, A2bAR and A3AR. With a
      knowledge of both the protein sequence of adenosine receptors and the structure
      of the A1AR gene, the function and regulation of these receptors can be further
      explored. Site-directed mutagenesis of the A1AR has resulted in the
      identification of amino acid residues in transmembrane domains 6 and 7 that are
      critical in both agonist and antagonist binding. The construction and analysis of
      A1/A3 chimeric receptors has also revealed regions of adenosine receptors
      important in ligand binding. These include the distal region of the second
      extracellular loop of adenosine receptors, which has a role in the binding of
      both agonist and antagonist ligands. A segment of the exofacial portion of the
      transmembrane domain 5 of adenosine receptors appears to be involved in the
      selective recognition of agonist ligands containing a substitution at the 5'
      position of the ribose moiety. Isolation of the genomic sequence of the human
      A1AR, in combination with analysis of the transcript distribution in several
      tissues, indicates that alternative splicing of the human A1AR occurs in the 5'
      untranslated region of the gene. Two distinct transcripts, containing either
      exons 3, 5 and 6 or exons 4, 5 and 6, exist with exons 3 and 4 apparently
      mutually exclusive. The exon 4, 5 and 6 transcript has been detected in all
      tissues that express the A1AR, while the exon 3, 5 and 6 mRNA is found in tissues
      that display a relatively high A1AR expression. Findings suggest that the
      presence of two ATG codons in exon 4, upstream of the translation start site, is
      involved in the repression of the A1AR expression in those tissues containing the
      exon 4, 5 and 6 transcript.

PMID- 7639616
TI  - Characterization of the adenosine receptors in the airways.
AB  - Adenosine causes bronchoconstriction both in vivo and in vitro in human
      asthmatics. In an in vivo rat model of adenosine-induced bronchoconstriction, the
      order of bronchoconstrictor potency of adenosine analogues was NECA = CPA > APNEA
      > CHA > R-PIA > CGS21680. This order of potency does not fit with the classical
      order of potency for a single subtype of adenosine receptors. The complete lack
      of bronchoconstrictory activity of CGS21680 suggests, nevertheless, that the A2A
      receptor subtype is not involved in the adenosine-induced bronchoconstriction. A
      remarkable finding was the dose-response curve to APNEA, which is thought to have
      some selective activity on the A3 receptor. The A2A-selective antagonist KF17837
      (10(-7) to 10(-5) mol/kg) had no significant inhibitory activity on the adenosine
      induced bronchoconstriction. The A1 antagonists, KF15372 and KW3902, both
      significantly inhibited the NECA-induced bronchoconstriction in BDE rats. We,
      therefore, conclude that the adenosine-induced bronchoconstriction in the rat is
      most likely due to binding of adenosine to different receptor subtypes including
      the A1, A2B and A3 subtypes.

PMID- 7639617
TI  - Tachykinin receptors and receptor subtypes.
AB  - The tachykinins, substance P, neurokinin A and neurokinin B, are a family of
      neuropeptides widely distributed in the mammalian central and peripheral nervous
      system. In the peripheral nervous system, tachykinins released from peripheral
      endings of sensory nerves are responsible for the neurogenic inflammation
      phenomenon. In the spinal cord/central nervous system, tachykinins play a role in
      pain transmission/perception and in some autonomic reflexes and behaviors. Their
      actions are mediated by three distinct receptors, termed NK1, NK2 and NK3. All
      tachykinin receptors belong to the superfamily of G protein-coupled receptors,
      with seven putative transmembrane spanning segments. In the past few years, a
      number of potent and selective antagonists, of both peptide and nonpeptide
      nature, has been developed for the NK1, NK2 and NK3 receptors. The contemporary
      isolation and cloning of the three tachykinin receptors enable now to study the
      molecular determinants for the interaction of natural tachykinins with their
      receptors, and the mechanism by which the antagonists interfere in this process.
      Furthermore, the introduction of tachykinin antagonists has revealed a striking
      species-related heterogeneity among the tachykinin receptors, and has also
      suggested a possible intra-species heterogeneity for both NK1 and NK2 receptors.
      However, molecular biology studies are needed to prove the existence of true
      tachykinin receptor subtypes.

PMID- 7639619
TI  - Proceedings of the 3rd Workshop on Nonadrenergic Noncholinergic Mechanisms.
      Ghent, September 22-23, 1994.

PMID- 7639618
TI  - Interplay of VIP and nitric oxide in the regulation of neuromuscular activity in
      the gut.

PMID- 7639620
TI  - Nitric oxide-mediated contraction in enteric smooth muscle.
AB  - Nitric oxide (NO) seems to be involved as neurotransmitter in nonadrenergic
      noncholinergic (NANC) smooth muscle relaxation throughout the gastrointestinal
      tract. Contractile responses to NO in the gastrointestinal smooth muscle have
      also been reported. In the guinea-pig ileal longitudinal muscle-myenteric plexus
      preparation at basal tone, NO induces a moderate relaxation followed by an
      aftercontraction; the latter is blocked by tetrodotoxin. The aftercontraction is
      also reduced by atropine, the remaining part being inhibited by a substance P
      antagonist. This indicates the activation of cholinergic and, possibly,
      tachykininergic neurons; it is not clear whether this represents a rebound
      phenomenon to the relaxation or a direct action of NO, initially masked by the
      relaxation. Nitrergic "off"-contractions, in response to electrical stimulation
      of the inhibitory NANC nerves, were reported in the opossum esophageal body and
      in the cat distal colon. Primary contractions to NO have been reported in the rat
      ileum and in the longitudinal muscle of the opossum esophagus. In the rat
      preparation, the contraction to NO is observed at lower concentrations than the
      relaxant effect. While the contraction in the opossum seems to be related to
      guanylate cyclase activation, this is not the case in the rat ileum, as methylene
      blue did not influence the contractions and 8-bromo-cGMP only had a relaxant
      effect. No clear-cut rise in cGMP was observed during the NO-induced contraction.
      The NO-induced contraction was also not influenced by ryanodine but it was
      concentration-dependently reduced by nifedipine, suggesting that it is related to
      extracellular calcium influx through L-type calcium channels. Primary
      contractions due to NO were also observed in the rat whole ileum and in the rat
      caecal longitudinal muscle, while aftercontractions, due to NO, were also
      obtained in the rat descending, transverse and sigmoid colon, as well as in the
      cat ileal longitudinal muscle.

PMID- 7639621
TI  - Sensory nerves, nitric oxide and NANC vasodilatation.
AB  - Primary afferent neurons, originating from the dorsal root ganglia, provide a
      perivascular network of fibres around the arterial system throughout the body.
      When stimulated, these fibres cause a nonadrenergic noncholinergic (NANC)
      vasodilatation by release of calcitonin gene-related peptide (CGRP). This peptide
      is a potent vasodilator and, in this action, cooperates with nitric oxide (NO) in
      a tissue-specific manner. The hyperaemic effect of intravascularly injected rat
      CGRP-alpha in the rat gastric mucosa is reduced by blockade of the NO synthesis,
      which indicates that CGRP dilates the gastric microvascular bed via NO-dependent
      and -independent mechanisms. This is also true for endogenous CGRP, as the
      gastric mucosal hyperaemia, which is caused by gastric acid challenge and
      involves CGRP, is likewise blocked by inhibition of the NO synthesis. The CGRP/NO
      mediated vasodilatation is an important element of a neural emergency system that
      strengthens the resistance of the gastric mucosa in the face of pending acid
      injury. In the rat skin, CGRP participates in neurogenic inflammatory processes
      but the cutaneous vasodilator action of exogenous CGRP and the CGRP-mediated
      vasodilatation, evoked by antidromic stimulation of afferent nerve fibres, do not
      depend on the formation of NO. This L-arginine-derived autacoid, however, plays a
      role in the release of CGRP from afferent nerve fibres in the skin since it
      contributes to the CGRP-mediated vasodilator responses to chemical irritation or
      immunological challenge via interleukin-1 beta. These data indicate that the type
      of interaction between CGRP and NO in causing a NANC vasodilatation varies with
      the vascular bed under study. Depending on the tissue, NO may facilitate the
      release of CGRP from afferent nerve fibres or be a secondary vasorelaxant
      messenger of the peptide.

PMID- 7639622
TI  - Nitric oxide and bronchial hyperresponsiveness.
AB  - Increasing evidence points to an important role for nitric oxide in the
      regulation of pulmonary functions and in pulmonary disease. In the respiratory
      tract, sensory nerves, endothelial cells, vascular and airway smooth muscle
      cells, inflammatory cells and the airway epithelium are sources of nitric oxide.
      Different nitric oxide synthases have been isolated, cloned and sequenced.
      Functionally, there are constitutive and inducible forms of nitric oxide
      synthase. A number of cytokines have been shown to inhibit or induce the
      expression of the inducible nitric oxide synthase. In human airways, endogenous
      nitric oxide appears to account for the bronchodilator nonadrenergic and
      noncholinergic response. Nitric oxide-containing vasodilators, such as glyceryl
      trinitrate and sodium nitroprusside, induce relaxation of the isolated airway
      smooth muscle, activate guanylate cyclase and raise c-GMP levels. Nitric oxide
      (constitutive), produced by the epithelial layer, appears to be important in
      blunting the histamine contractile response of the airway tissue. Furthermore,
      tracheal relaxation by, e.g., bradykinin or potassium chloride, is mediated by
      the release of nitric oxide. The virus (Parainfluenza type 3)-induced airway
      hyperreactivity in guinea-pigs is correlated with a deficiency in endogenous
      constitutive nitric oxide production by the airways and can be blocked by low
      doses of L-arginine. In inflamed tissue, nitric oxide quickly reacts with
      superoxide anion, resulting in the formation of the toxic peroxynitrite which
      promotes lipid and sulfhydryl oxidation. Asthmatic patients have higher amounts
      of nitric oxide in the expired air, possibly due to the inflammation. This
      increased nitric oxide production can be inhibited by inhaled corticosteroids.
      The effect of inhaled nitric oxide on the lung function of asthmatic patients is
      variable. In contrast, low doses of inhaled nitric oxide are effective in
      reversing the pulmonary vasoconstriction. These results point to an important
      role for nitric oxide in modulating airway reactivity.

PMID- 7639624
TI  - Anterograde memory impairment in Pick's disease.

PMID- 7639623
TI  - Nitric oxide as a neurotransmitter in human airways.
AB  - Human airway smooth muscle possesses a prominent nonadrenergic noncholinergic (i
      NANC) bronchodilator response. Nitric oxide (NO) appears to account for all the i
      NANC response in human central and peripheral airways in vitro. Furthermore, it
      appears that i-NANC relaxations in human trachea are associated with a
      concomitant selective elevation of cGMP, but not cAMP levels, which are inhibited
      by an NO synthase (NOS) inhibitor. This confirms the hypothesis that the L
      arginine/NO/cGMP pathway is responsible for mediating the i-NANC response in this
      tissue. It is not certain from where the NO is formed or the location of the NOS
      enzyme. However, in human trachea, NOS immunoreactivity (NOS-IR) has been
      described in nerve fibres originating from intrinsic neurons. In addition, the
      density of NOS-IR is reduced from proximal to distal airways and this correlates
      with functional data describing a reduced i-NANC relaxation response from central
      to peripheral airways. The i-NANC bronchodilator nerves are the only neural
      relaxant pathway in human airways and, therefore, it is important to determine
      whether there is any defect in the ability of these nerves to function in
      diseased airways. In fact, functional and immunohistochemical data suggest that
      there may be a deficiency in NOS-IR nerves leading to a decreased i-NANC response
      in tissue from patients with cystic fibrosis. NOS inhibitors appear to enhance
      the cholinergic bronchoconstriction in human airways in vitro. Therefore, if the
      nitrergic innervation is dysfunctional in inflammatory conditions, its absence
      may lead to exaggerated bronchoconstriction.

PMID- 7639625
TI  - Similar disorders viewed with different perspectives.

PMID- 7639626
TI  - Correlations between triplet repeat expansion and clinical features in
      Huntington's disease.
AB  - OBJECTIVE: To investigate possible correlations between the length of the (CAG)n
      trinucleotide repeat in Hungtington's disease gene IT15 and clinical features
      (age at onset, symptoms at onset, and mode of progression) in Huntington's
      disease. DESIGN: In 59 patients with Huntington's disease, the expansion of the
      (CAG)n trinucleotide repeat was determined and clinical data were obtained
      retrospectively. SETTING: The Center for Human Genetics, affiliated with a
      university hospital. PATIENTS: All patients belonged to an initial group of 248
      individuals tested in an indirect predictive testing procedure. RESULTS: A good
      correlation was found between the expansion of the (CAG)n trinucleotide repeat
      and the age at onset (r = -.71). No correlation was found between the repeat
      length of the normal allele and the age at onset. No correlations were found
      between repeat expansion and other clinical features, such as the nature of the
      symptoms at onset (neurologic, psychiatric/cognitive, or both) and the mode of
      progression. CONCLUSION: Factors that determine the nature of symptoms at onset
      and the mode of progression of Huntington's disease seem to be operating
      independently of the (CAG)n trinucleotide repeat in gene IT15.

PMID- 7639627
TI  - Measuring patient-centered outcomes in neurologic disease. Extending the Q-TWiST
      method.
AB  - BACKGROUND: Current clinical research and outcomes assessment on multiple
      sclerosis rely on an approach to disability measurement that is heavily
      influenced by ambulation. Not only is this strategy often insensitive to the
      clinical changes affected by pharmacotherapeutic or rehabilitative interventions
      but it also disregards the symptoms that patients seem to consider most
      enervating. We propose a new method for evaluating clinical interventions in
      terms of their impact on the symptoms of multiple sclerosis, side effects,
      parameters of exacerbation, and disease progression, while considering the
      patient's perspective. METHODS: The extended Q-TWiST method yields an estimation
      of treatment trade-offs in terms of Quality-adjusted Time Without Symptoms and
      Toxicities (Q-TWiST). An illustration of this method is presented by using a
      hypothetical clinical trial of two treatments. The trade-offs between the two
      treatments are highlighted to facilitate treatment decision making by using
      individual patient importance weights. CONCLUSION: We discuss applications to
      other clinical research and other chronic diseases.

PMID- 7639628
TI  - Alzheimer's disease in the National Academy of Sciences-National Research Council
      Registry of Aging Twin Veterans. III. Detection of cases, longitudinal results,
      and observations on twin concordance.
AB  - OBJECTIVES: To detect cases of Alzheimer's disease (AD) in a large population of
      twins living throughout the United States and to examine concordance for AD in
      twins as a function of age and genotype for apolipoprotein E (APOE). SETTING:
      Nationwide survey. DESIGN: Multistage screening and field evaluation beginning
      with two telephone interviews and culminating with laboratory tests, longitudinal
      neuropsychological measures, physician examination, and diagnostic consensus
      among experts. PARTICIPANTS: Membership in 1990-1991 of intact pairs in the
      National Academy of Sciences--National Research Council Registry of veteran
      twins, then aged 62 to 73 years. MAIN OUTCOME MEASURES: Completeness of case
      detection was examined in collateral studies. Zygosity and APOE genotypes were
      determined by restriction mapping. Concordance was calculated by the proband
      method. RESULTS: Ninety subjects who screened positively for AD were studied in
      person, and 60 whose differential diagnoses included AD were followed up, as were
      their co-twins. Sensitivity of screening was estimated at greater than 99%, but
      24% of subjects refused participation after initial screening. Seven of 38
      diagnoses of AD have been confirmed at autopsy, and 31 other subjects eventually
      met criteria for probable or possible AD (prevalence estimate, 0.42%, 95%
      confidence interval, 0.29% to 0.56%), with good interrater reliability
      (intraclass r = .86). Excluding one discordant pair with unknown zygosity,
      concordance rates were 21.1% (4/19) for monozygotic and 11.1% (2/18) for
      dizygotic probands. Concordance was 50% for twins sharing the epsilon 4/epsilon 4
      genotype at APOE, but there were no affected co-twins of 15 probands with onset
      before age 70 years, no epsilon 4 allele, and no family history of AD. The mean
      (SD) period of discordance in the latter pairs was 11.3 (3.3) years. CONCLUSIONS:
      The multistage case-detection approach achieved reliable and valid diagnoses of
      AD with high apparent sensitivity but substantial attrition after initial
      screening. Genetic influences in AD at this age are limited, except among
      homozygotes for allele epsilon 4 at APOE. Subjects with early-onset AD who lack
      the epsilon 4 allele are not rare, and their condition appears to have little
      genetic influence. They should be ideal for studies on environmental cause of AD.

PMID- 7639631
TI  - Reduced size of corpus callosum in autism.
AB  - OBJECTIVE: To determine via magnetic resonance imaging if the posterior corpus
      callosum is reduced in the midline cross-sectional area in autistic patients,
      consistent with previous reports of parietal lobe abnormalities. DESIGN: Case
      control study. SETTING: Tertiary care facility. PATIENTS AND OTHER PARTICIPANTS:
      Fifty-one autistic patients (45 males and six females; age range, 3 to 42 years),
      including both mentally retarded and nonretarded patients who met several
      diagnostic criteria for autism were prospectively selected. Fifty-one age-and sex
      matched volunteer normal control subjects were also included. INTERVENTION: None.
      MAIN OUTCOME MEASURES: Computer-aided measurement of cross-sectional area, areas
      of five subregions, and thickness profile. RESULTS: Overall size reduction,
      concentrated in posterior subregions. CONCLUSIONS: Evidence is found of a reduced
      size of the corpus callosum in autistic patients. This reduction is localized to
      posterior regions, where parietal lobe fibers are known to project. This finding
      further supports the idea that parietal lobe involvement may be a consistent
      feature in autism.

PMID- 7639629
TI  - Cortical abnormalities associated with subcortical lesions in vascular dementia.
      Clinical and position emission tomographic findings.
AB  - OBJECTIVE: To examine the effects of subcortical lesions on cortical metabolic
      rate and clinical symptoms in patients with vascular dementia. METHOD: Eleven
      elderly patients with vascular dementia who demonstrated no lesion involving the
      cerebral cortex on magnetic resonance imaging underwent 18F-fluorodeoxyglucose
      positron emission tomography to assess global cortical metabolism and metabolic
      activity in each cortical lobe. Subcortical lesions on magnetic resonance imaging
      (periventricular hyperintensities, deep white matter hyperintensities, and
      subcortical lacunar infarcts) were measured using a graded scale of severity.
      Cognitive and noncognitive symptoms were assessed with the Neurobehavioral Rating
      Scale. RESULTS: Reduced cortical metabolism was generally associated with the
      severity of subcortical pathologic changes, but there was substantial
      heterogeneity in the relationship between subcortical lesions and cortical
      metabolic activity. Mean global cortical metabolism was lower in patients with
      periventricular hyperintensities in anterior subcortical regions than in those
      without such lesions. The metabolic rate in the frontal cortex was lower in
      patients with a lacunar infarct of the basal ganglia or thalamus than in those
      without. Neurobehavioral Rating Scale total score, the Verbal Output Disturbance
      factor score, and the Anxiety/Depression factor score were correlated with the
      severity of white matter lesions. CONCLUSIONS: Cortical metabolic dysfunction is
      related to ischemic subcortical lesions in patients with vascular dementia.
      Metabolism in the frontal cortex may be particularly dependent on pathologic
      alterations of subcortical nuclei. Anxiety, depression, and the overall severity
      of neuropsychiatric symptoms in vascular dementia are associated with the extent
      of white matter ischemia.

PMID- 7639630
TI  - The predictive value of cerebrospinal fluid dynamic tests in patients with th
      idiopathic adult hydrocephalus syndrome.
AB  - OBJECTIVE: To evaluate the predictive value of the cerebrospinal fluid (CSF) tap
      test and CSF outflow conductance in the selection of patients with the idiopathic
      adult hydrocephalus syndrome, defined exclusively on a clinical basis, for shunt
      surgery. DESIGN: A prospective, consecutive case series. All patients were
      assessed before surgery and at 3 months after shunt placement. Preoperatively,
      CSF pressure, conductance, and CSF formation rate were assessed by a constant
      pressure infusion method. Improvement in gait and cognitive functions after
      removal of CSF was noted (ie, with the CSF tap test). Postoperatively, the
      infusion method was used to evaluate shunt function. SETTING: Tertiary, academic
      referral center. PATIENTS: Thirty-five patients with idiopathic adult
      hydrocephalus (normal-pressure hydrocephalus) syndrome based on conservative
      clinical criteria. No predictive tests were used for inclusion. All patients had
      a typical gait disturbance and a communicating hydrocephalus. Twenty-eight
      patients also had dementia or incontinence, or both. INTERVENTION: The CSF
      diversion (Cordis, [Orbis-Sigma]) valve, six patients; Hakim's standard system
      (Cordis Hakim standard system), 29 patients. OUTCOMES OF SURGERY: Serial
      videotaping of gait, a comprehensive neuropsychologic battery, and the Bartel
      index of activities of daily life. RESULTS: Gait was improved in 25 (72%) of the
      35 patients, whereas the Bartel index remained unchanged. The conditions of five
      of seven patients with gait disturbance as the sole symptom improved. The spatial
      function (37% improved) and the findings from the Fuld object memory tests (29%
      improved) were significantly improved. Shunt dysfunction could not explain the
      lack of effect of an operation in the remaining patients. It should be noted that
      these results obtained at 3 months postoperatively may not be applicable in a
      long-term perspective. The CSF outflow conductance or CSF tap test were not able
      to identify those patients who would or would not benefit from a CSF diversion
      procedure. However patients had a lower conductance and a higher CSF pressure
      than did control subjects. CONCLUSIONS: Considerable improvement in gait was
      seen, but cognitive function was little affected. The CSF tap test or conductance
      does not provide additional information that is necessary to distinguish between
      patients whose conditions will or will not respond to shunting, when selection
      for surgery is based on conservative clinical criteria.

PMID- 7639632
TI  - Psychogenic parkinsonism.
AB  - BACKGROUND: Parkinsonism resulting from a primary psychiatric disorder has not
      been well characterized previously. We had been impressed that this was a rare
      but definite cause of parkinsonism in patients presenting to our subspecialty
      movement disorders clinics. OBJECTIVE: To define the clinical characteristics of
      "psychogenic parkinsonism" to assist in the differentiation of these patients
      from those with "organic" parkinsonian disorders. DESIGN: Retrospective chart
      reviews of patients seen at three large movement disorders centers. PATIENTS:
      Seven men and seven women were diagnosed as having "documented" or "clinically
      established" psychogenic parkinsonism after repeated assessments. RESULTS: Tremor
      (12 patients) was present at rest but continued without the usual transient
      dampening on taking up a posture and persisted with action. Tremor frequency and
      rhythmicity varied markedly. Tremor could often be entrained to the frequency of
      other movements or subsided with distraction. Rigidity (six patients) had
      features of voluntary resistance, often decreasing with distraction and/or
      activating synkinetic movements in opposite limbs. Arm swing was usually
      diminished or absent on the affected side; however, the arm could be held tightly
      to the side or cradled in front of the patient. Slowness of movement (all 14
      patients) usually lacked the typical decrementing amplitude feature of
      bradykinesia. The slowness, ambulatory abnormalities, and postural instability
      (12 patients) often had bizarre, inconsistent, or incongruous features.
      Functional "give-way" weakness and nonorganic sensory disturbances were common
      (10 patients). Spontaneous remissions and remissions with placebo treatment or
      psychotherapy and response fluctuations related to unusual interventions were
      occasionally seen (five patients). Underlying psychological factors varied
      considerably. Most patients had been seen by several physicians and had undergone
      multiple unrevealing investigations. Fluorodopa F 18 (F-dopa) positron emission
      tomographic scanning yielded normal findings in three patients. Abnormal positron
      emission tomographic scanning results in a fourth patient, whose signs and
      symptoms had improved with psychotherapy and haloperidol therapy, emphasizes the
      possibility that prominent psychogenic features may be superimposed on organic
      parkinsonism in some patients. CONCLUSION: Psychogenic parkinsonism occurs
      rarely. It is a diagnosis of exclusion that should be made only by physicians
      with considerable experience in the care and treatment of patients with
      parkinsonism.

PMID- 7639633
TI  - Immunological and clinical response to immunosuppressive treatment in
      paraneoplastic cerebellar degeneration.
AB  - OBJECTIVE: To report the clinical and immunological response to immunosuppressive
      treatment with cyclophosphamide in two patients with paraneoplastic cerebellar
      degeneration. DESIGN: Case reports. Clinical and immunological follow-up data
      available for 4 1/2 years in the first patient and for 2 years in the second
      patient. SETTING: A 1500-bed university hospital and a 1200-bed university
      teaching hospital. INTERVENTION: Cyclophosphamide intermittent treatment. MAIN
      OUTCOME MEASURE: Clinical disability. RESULTS: One of the patients, who was
      treated from an early stage, recovered completely. The other patient showed a
      partial clinical response. While the two patients were receiving a maintenance
      regimen with cyclophosphamide, the conditions of both patients remained stable
      for at least 2 years. In both patients, intrathecal antibody synthesis declined
      considerably. CONCLUSION: Early induction of immunosuppressive therapy with
      cyclophosphamide should be tried in treating patients with paraneoplastic
      cerebellar degeneration.

PMID- 7639634
TI  - Hippocampal volumetrics differentiate patients with temporal lobe epilepsy and
      extratemporal lobe epilepsy.
AB  - OBJECTIVE: To determine whether the occurrence of hippocampal formation (HF)
      volumetric asymmetry can reliably discriminate between complex partial seizures
      (CPSs) of a temporal lobe origin and CPSs of an extra-temporal lobe origin in a
      prospective study of patients with intractable CPSs (approximately 70% of
      patients have electrographic foci in the temporal lobe [HF volumetric asymmetry
      on magnetic resonance imaging scans has been shown to lateralize such foci
      reliably)]. DESIGN: We examined HF volumetrics on magnetic resonance imaging
      scans that were acquired with a 1-T magnetic resonance imaging scanner (Siemens
      Magnetom, Siemens Medical Systems, Iselin, NJ) by using magnetization-prepared
      rapid gradient echo three-dimensional sequences (producing a gapless series of
      high-contrast 1.25-mm images). These data were compared with ictal, interictal,
      invasive, and noninvasive videoelectroencephalographic monitoring data,
      functional imaging data, and outcome data to define each patient's type of
      epilepsy. SETTING AND PATIENTS: Forty-one patients were recruited from a tertiary
      university comprehensive epilepsy program, and 22 control subjects were recruited
      from the neurologically normal university community. RESULTS: Among the control
      subjects, the difference in HF volumetrics (right-left HF volumetrics) was +
      0.085 +/- 0.253 cm3. Of the 41 patients, 25 had temporal lobe epilepsy. When we
      set the upper limit of normal at the mean +/- 3 SDs, all patients beyond the
      upper limit had CPSs of a temporal lobe origin. Of the patients with temporal
      lobe epilepsy, only three fell within normal limits. No patient with CPSs of an
      extratemporal lobe origin fell beyond the upper limit. CONCLUSION: The presence
      of significant HF volumetric asymmetry makes it highly unlikely that a patient's
      CPSs are of an extratemporal lobe origin.

PMID- 7639635
TI  - Dystonia and unique muscle features. A 23-year follow-up and correction of
      diagnosis in two brothers.
AB  - OBJECTIVE: To provide follow-up information and a corrected diagnosis on two
      brothers who were primarily described in the ARCHIVES in 1971 as having had a
      genetic dystonia with unusual muscle biopsy features. MEASURES: Clinical
      observation of response to treatment and muscle histologic findings. RESULTS:
      These brothers are an unusual example of dopa-responsive dystonia that was
      present since birth. The muscle histopathologic features were caused by an
      abnormal cerebral influence on the developing motor unit and were not a primary
      abnormality. A repeated muscle biopsy performed 1 year after treatment continued
      to show the same pattern of fiber-type abnormalities. CONCLUSIONS: Dopa
      responsive dystonia can be present from birth or early infancy. The response to
      levodopa is excellent even after a delay in treatment of more than 20 years.
      Intrauterine dystonia can cause a predominance of small type 2 fibers. A trial of
      levodopa/carbidopa is indicated in all patients with a childhood-onset dystonia
      or gait disturbance.

PMID- 7639636
TI  - The identification by imaging methods of patients who might benefit from carotid
      endarterectomy.

PMID- 7639637
TI  - Angiography before carotid endarterectomy--no.

PMID- 7639638
TI  - The issue is standards, not techniques.

PMID- 7639639
TI  - The role of brain acetylcholine in phenol-induced tremor in mice.
AB  - The relation between phenol-induced tremor and brain acetylcholine levels, and
      the effects of cholinergic drugs on the tremor were investigated, using male ddY
      mice weighing 28-35 g. The magnitude of phenol-induced tremor was graded on a 4
      point scale: 0, normal; 1, slight; 2, moderate; 3, severe, and acetylcholine
      levels were measured by high-performance liquid chromatography with
      electrochemical detection. The magnitude of tremor and the decrease in
      acetylcholine levels in the striatum and cerebral cortex induced by s.c.
      injection of phenol (50, 100, 200 mg/kg) were dose-dependent, and both showed
      parallel time courses. Intracerebroventricular (i.c.v.) injection of phenol (100
      micrograms/mouse) caused a decrease in acetylcholine levels in the striatum but
      did not induce tremor. Intraperitoneal injection of pentobarbital (10 mg/kg),
      which inhibits the release of acetylcholine, weakened both the magnitude of the
      tremor and the decrease in acetylcholine levels induced by phenol (200 mg/kg),
      whereas i.c.v. injection of pentobarbital (120 micrograms/mouse) attenuated the
      decrease in acetylcholine levels induced by phenol, but did not affect the
      magnitude of the tremor. Intraperitoneal (20 mg/kg) or i.c.v. (60
      micrograms/mouse) injection of mecamylamine further strengthened the tremor.
      Intraperitoneal (0.3 mg/kg) injection of physostigmine strengthened the tremor,
      while i.c.v. injection (1 microgram/mouse) caused a reduction in its magnitude.
      These results suggest that the tremor is caused directly by the phenol-induced
      increase in acetylcholine release in the peripheral nervous system (motor nerve
      endings), that the decrease in brain acetylcholine levels may be due to phenol
      induced increases in acetylcholine release within the central nervous system, and
      that the resultant reduction in brain acetylcholine levels indirectly suppresses
      the tremor.

PMID- 7639640
TI  - The reinnervation of the tongue and salivary glands after two methods of lingual
      nerve repair in the cat.
AB  - The recovery of fibres in the chorda tympani after repair by epineurial suture or
      entubulation was investigated. The combined trunk of the chorda tympani and
      lingual branch of the trigeminal nerve was sectioned unilaterally, repaired using
      either epineurial sutures or entubulation, and allowed to recover for 12 weeks.
      The properties of gustatory, thermosensitive and mechanosensitive units, and the
      return of vasomotor and secretomotor responses were then investigated. After
      repair by epineurial suture, integrated whole-nerve activity recorded from the
      chorda tympani during stimulation of the tongue with gustatory or thermal stimuli
      was reduced in all areas of the tongue when compared to controls. After
      entubulation repair, little or no activity could be recorded. Recordings made
      from 57 single units in the chorda tympani after repair by epineurial suture
      revealed a greater proportion of purely mechanosensitive units and fewer
      gustatory units than in the controls. Fewer units were spontaneously active, they
      had lower maximum discharge frequencies, and produced fewer impulses when
      stimulated. Recordings made from 61 single units after repair by entubulation
      revealed receptor characteristics with greater differences from controls than
      after epineurial suture and there was only one gustatory and one thermosensitive
      unit. Vasomotor responses were completely restored after repair by epineurial
      suture, but some responses were smaller after entubulation repair. Secretomotor
      responses were significantly smaller after both methods of repair and there was
      no difference between the two groups.

PMID- 7639641
TI  - Calcium and water diffusion in single-species model bacterial plaques.
AB  - The diffusion of tritiated water and 45Ca through single-species model plaques
      was measured in a diaphragm cell. Using plaques of Streptococcus downei, the
      apparent diffusion coefficient for tritiated water showed a small but significant
      decrease between pH 7.0 and 5.0 with a smaller, non-significant decrease for
      calcium. These effects are attributed to possible plaque shrinkage at reduced pH,
      which overcomes effects due to charge-dependent changes in permeability.
      Effective diffusion coefficients for 45Ca obtained from lag-time measurements
      were much reduced at low carrier concentrations, demonstrating a binding which
      correlated with previous results from equilibrium dialysis. Strep. sanguis and
      Corynebacterium matruchotii showed few differences from Strep. downei, although
      the corynebacterium previously demonstrated stronger calcium binding.
      Permeability to water and calcium were slightly affected by pH, while effective
      diffusion of calcium depended on concentration. This may have important
      implications for the process of mineral loss in dental caries.

PMID- 7639642
TI  - Changes in extracellular matrix macromolecules in human gingiva after treatment
      with drugs inducing gingival overgrowth.
AB  - It is generally agreed that gingival overgrowth results from an increase in the
      levels of gingival extracellular macromolecules infiltrated with various numbers
      of inflammatory cells. The relative amounts of extracellular matrix
      macromolecules observed in 12 cases of gingival hyperplasia associated with the
      use of cyclosporin, hydantoin or nifedipine were compared with those obtained in
      a control group on the basis of histological and immunohistochemical
      investigations. From tissue sections, the quantification was by computerized
      morphometric analysis on a BFM 186 microcomputer to which were implemented the
      transformations of mathematical morphology. The area fractions (AA%) occupied by
      total collagen, type III and type IV collagen, vessels, fibroblasts, fibronectin
      and elastic fibres were estimated and compared. The overall histological aspects
      of drug-induced gingival overgrowth were similar, but quantification of different
      extracellular matrix components showed differences. In the nifedipine and
      cyclosporin groups, the area occupied by fibroblasts were not significantly
      greater than in healthy gingiva and chronic gingivitis. The area occupied by
      collagen was significantly greater in the nifedipine group than in the other
      pathological groups. Fibronectin was also strongly expressed in the nifedipine
      group, and the elastic fibre network was preserved in this group.

PMID- 7639643
TI  - Swallow thresholds in human mastication.
AB  - Brazil-nut particles were broken down and classified by sieves into four classes
      of particle size. Samples of these classes were suspended in plain yoghurt in
      varying concentrations and presented to nine humans for chewing. Both the number
      of chews made before swallowing and the time needed to swallow increased
      significantly with particle size and concentration but the chewing frequency
      (number of chews/time) decreased. The rate of change of the chewing frequency,
      averaged over the chewing sequence (chewing frequency/time), was calculated for
      each food input and termed the swallowing index. This index did not differ
      significantly for concentrations above 20%, but increased sharply at lower
      concentrations. These results were interpreted in terms of a model in which food
      is swallowed only when particles are both small enough and sufficiently
      lubricated. For our food mixture, the lubrication threshold was satisfied by a
      20% concentration and the particle-size threshold was 1.4 mm. Chews made with
      concentrations lower than this and containing smaller particle sizes were few in
      number and slow, reflecting the need to detect particle size with the oral
      mucosa.

PMID- 7639644
TI  - Myosin expression in the jaw-closing muscles of the domestic cat and American
      opossum.
AB  - Sodium dodecylsulphate-polyacrylamide gel electrophoresis (SDS-PAGE), glycerol
      SDS-PAGE, two-dimensional electrophoresis, and protein immunoblotting techniques
      were used to identify myosin heavy chain (MHC) and light chain (MLC) isoforms in
      limb and masticatory muscles of the cat and American opossum. The fibre types in
      which these isoforms are expressed were identified by histochemistry and
      immunohistochemistry. Antibodies specific for the type IIM MHC isoform
      characteristic of cat jaw-closing muscles and the type I MHC isoform were
      produced and characterized. The IIM antibody stained the majority of fibres found
      in the jaw-closing muscles of both species. These IIM-containing fibres
      characteristically had a histochemical ATPase that remained active after both
      acid and alkali pre-incubations. A minority of type I fibres was also present in
      cat jaw-closing muscles, and these reacted positively with antibody specific for
      type I MHC. It was confirmed that the vast majority of fibres in the cat jaw
      closing muscles contained only the characteristic masticatory MHC (IIM) and
      masticatory MLCs (LC1m and LC2m). These muscles did not contain either the type
      II fibre isoforms of limb muscles or the atrial cardiac (alpha-cardiac) MHC. The
      type IIM MHC could also be identified in jaw-closing muscles of the opossum. Two
      dimensional gel electrophoresis was used to identify the MLC composition of
      single, histochemically defined, type I fibres in the cat soleus and deep
      masseter. The type I fibres of limb muscle contained the usual slow MLCs, but
      type I fibres from the jaw-closing muscles contained only the masticatory light
      chains.

PMID- 7639645
TI  - Bite force displayed during assessment of hardness in various texture contexts.
AB  - The relationship between mastication pattern, mechanical properties of the food
      bolus and texture perception are not fully understood, though the mastication
      process is known to adjust to different textural properties of foods. This study
      investigated the role of the bite force as one major aspect in hardness
      assessment of materials exhibiting simple mechanical properties over a wide
      hardness range. Elastic, plastic and brittle materials (silicone elastomers,
      waxes and pharmaceutical tablets, respectively) were tested. The rheological
      characteristics of these products were measured. For each product, one to four
      differential thresholds were determined at different points on a hardness scale
      by 10 individuals free of dental pathology. Bite forces were recorded by placing
      a small intraoral load cell under each sample. To assess the influence of the
      nature of the applied force, bites were made either directly on to the sample or
      on a metal disc placed between the teeth and the sample. As the individuals had
      to break the brittle products to perceive any hardness difference, bite forces
      were very closely correlated with the hardness of the products (r = 0.99). For
      plastic products, bite forces again correlated with the hardness (r = 0.96), even
      though individuals could stop biting at any time during the plastic deformation.
      Hardness perception of brittle and plastic products depends directly on sensory
      information about the bite force. However, hardness assessment of elastic
      products was obtained under constant bite force; here, the resulting deformation
      may provide sensory information about hardness.

PMID- 7639646
TI  - Effect of lipids on glycoprotein sulphotransferase activity in rat submandibular
      salivary glands.
AB  - Although glycoprotein sulphation has been implicated in the processing of
      salivary mucin, little is known about the regulation of the enzyme responsible
      for this event. Using desulphated glycoprotein as sulphate acceptor, the
      glycoprotein sulphotransferase (GPST) from Golgi membranes of submandibular
      salivary gland was used to study the effect of various lipids on its activity.
      The GPST activity in the Golgi membrane was 0.7 pmol/mg protein per min and the
      activity was extractable by Triton S-100. The Km of the solubilized GPST for
      glycoprotein and 3'-phosphoadenosine 5'-phosphosulphate (PAPS) were 11 and 0.2
      microM, respectively. Among the various lipids tested, phosphatidylinositol and
      sphingosine stimulated the GPST activity, while other lipids such as
      sphingomyelin, phosphatidylcholine and phosphatidylserine did not produce a
      significant effect. At 12 mol% (when expressed as mol% of sphingosine to total
      phospholipids plus Triton X-100) of sphingosine concentration, the enzyme
      activity was increased nearly 1.7-fold. The stimulatory effect of sphingosine was
      accompanied by a significant decrease in Km for glycoprotein from 11 to 2 microM
      but the increase in Vmax was small. In contrast, the sphingosine effect did not
      change the Km for PAPS but increased the Vmax nearly two fold. Of the two
      sphingosine analogues tested, threosphinganine and erythrosphinganine had a
      lesser stimulatory effect than sphingosine. Stearylamine was partially active,
      whereas the amino acids (glutamate, aspartate, glutamine, asparagine and serine)
      were not. These observations and our earlier finding of tyrosylprotein
      sulphotransferase inhibition by sphingosine demonstrate diverse sphingosine
      effects on the post-translational sulphation involved in the processing of
      salivary proteins and suggest an important role for sphingosine in the regulation
      of salivary protein sulphation.

PMID- 7639647
TI  - Proton microprobe assessment of the distribution of fluoride in the enamel and
      dentine of developing central incisors of sheep and changes induced by daily
      fluoride supplements.
AB  - Ten sheep were given 0.5 mg fluoride (F) and 10 sheep 0.2 mg F/kg body wt orally
      for periods of 1-6 months while 8 sheep received no additional F. One incisor
      from each sheep was sectioned longitudinally in the midline and, using the proton
      microprobe, multiple scans for calcium and F were made across the enamel and
      dentine. F was determined by proton-induced gamma-ray emission and calcium by X
      ray emission. Tooth length and hence the stage of ameloblast activity for each of
      the 28 teeth at the start of the experiment was determined using a tetracycline
      marker. In addition, the stage of enamel development of the eight control teeth
      (no dietary F) at the time of their extraction was assessed from their
      macroscopic appearance. Continuous changes in F levels occurred in both enamel
      and dentine throughout tooth development and also in the mature enamel and
      associated dentine after ameloblast regression. All scans for all stages of tooth
      development and all F treatments showed a high F concentration at the enamel
      surface. Early in the secretory phase, a wide-based F peak occupied the entire
      width of the enamel with a similar F peak in the dentine. In the control teeth,
      no consistent increase in F concentration occurred at the enamel surface during
      later development. When F supplements were started early in the maturation phase
      an increase in F concentration only at the enamel surface was recorded. When F
      supplements were also given during the secretory phase, higher F concentrations
      were recorded not only at the enamel surface but also for the inner enamel and
      dentine plateau. These findings, based on a small number of sheep, indicate that
      further research is needed to clarify the method and control of F uptake and to
      determine the changes in these processes during the different stages of tooth
      development.

PMID- 7639648
TI  - A histochemical study of carbonic anhydrase in the plasma membranes of human oral
      epithelial cells.
AB  - Carbonic anhydrase (EC 4.2.1.1) was detected histochemically from the following
      regions in patients of various ages (14-84 yr): buccal mucosa, buccal flap, hard
      palate and tongue. The enzyme was principally located in the cell membranes but
      was also present in nuclei. There was a gradation in activity from basal (strong)
      to superficial cells (weak/negative). The carbonic anhydrase inhibitors
      ethoxyzolamide and acetazolamide abolished activity at 0.001 mM, but were
      ineffective, even at 1.2 mM, against a reaction associated with the granules of
      the stratum granulosum. No activity was detected in the absence of bicarbonate
      from the substrate.

PMID- 7639649
TI  - Micromorphometric analysis of cervical enamel structure of human upper third
      molars.
AB  - Fifty-two teeth were sectioned and embedded such that the structural
      characteristics of the palatal enamel could be examined by scanning electron
      microscopy. Measurements were made of the height of aprismatic cervical enamel,
      of cervical enamel with atypically shaped prisms, and of cervical enamel without
      Hunter-Schreger bands. Enamel thickness 80, 1000 and 2500 microns occlusally from
      the cervical enamel border, the maximum thickness of cervical enamel with
      atypical prism shape and that of aprismatic cervical enamel, and the thickness of
      occlusal enamel were also measured. The height of cervical enamel with atypical
      prism shape ranged between 103 and 756 microns, and was inversely related to the
      thickness of typically structured enamel, suggesting that atypical enamel
      formation follows some order. Atypical enamel in the cervical area may affect
      caries susceptibility as well as the efficacy of acid-etching in this region.

PMID- 7639651
TI  - A double-masked, randomized 1-year study comparing dorzolamide (Trusopt),
      timolol, and betaxolol. International Dorzolamide Study Group.
AB  - OBJECTIVE: To investigate the safety profile and efficacy of 2.0% dorzolamide
      hydrochloride, when administered three times daily for up to 1 year, compared
      with that of 0.5% timolol maleate and 0.5% betaxolol hydrochloride, each
      administered twice daily. In addition, the effect of adding dorzolamide to the
      regimen of patients with inadequate ocular hypotensive efficacy while they were
      receiving one of the two beta-adrenoceptor antagonists and the effect of adding
      timolol to the regimen of patients receiving dorzolamide were also evaluated.
      DESIGN: A double-masked, randomized, parallel comparison. SETTING: Multinational
      study at 34 international sites. PATIENTS: Five hundred twenty-three patients
      with open-angle glaucoma or ocular hypertension, 17 to 85 years of age. Patients
      currently using ocular hypotensive medications were required to undergo a
      washout. INTERVENTION: Two percent dorzolamide three times a day, 0.5% timolol
      (Timoptic, Merck, Whitehouse Station, NJ) twice daily, and 0.5% betaxolol
      solution (Betoptic, Alcon, Fort Worth, Tex) twice daily. RESULTS: At 1 year, the
      mean percent reduction in intraocular pressure at peak of 2% dorzolamide, 0.5%
      timolol, and 0.5% betaxolol was approximately 23%, 25%, and 21%, respectively. At
      afternoon trough, the mean percent reduction in intraocular pressure was 17%,
      20%, and 15% for dorzolamide, timolol, and betaxolol, respectively. CONCLUSIONS:
      The ocular hypotensive efficacy of 2.0% dorzolamide, given three times a day, is
      comparable with that of 0.5% betaxolol, given twice daily, for up to 1 year. In
      addition, long-term use of dorzolamide was not associated with clinically
      meaningful electrolyte disturbances or systemic side effects commonly observed
      with the use of oral carbonic anhydrase inhibitors.

PMID- 7639650
TI  - Neural rim area declines with increased intraocular pressure in urban Americans.
AB  - OBJECTIVE: To determine intraocular pressure (IOP)-related differences in the
      neural rim area among urban Americans without known optic nerve disease. DESIGN:
      Population-based prevalence study conducted in 16 cluster areas in East
      Baltimore, Md. PARTICIPANTS: A population-based sample of 1521 black and 1851
      white individuals aged 40 years and older without evidence of optic nerve
      disease. MAIN OUTCOME MEASURE: Intraocular pressure-related differences in neural
      rim area, neural rim area-to-disc area ratio, and cup-to-disc ratio. RESULTS: We
      analyzed optic disc photographs using the Imagenet system (Topcon Instrument Corp
      of America, Paramus, NJ). After adjusting for age and disc area, white Americans
      had a 6% decrease in neural rim area for every 10-mm Hg increase in IOP (P =
      .0001). In black Americans, there was a quadratic relationship between neural rim
      area and IOP, with little decline with IOP up to approximately 17 mm Hg, after
      which neural rim area declined significantly with higher IOP (P = .001).
      Similarly, the neural rim area-to-disc area ratio decreased and the vertical cup
      to-disc ratio increased with increasing IOP in both black and white Americans.
      CONCLUSIONS: The higher the level of IOP, the smaller was the amount of neural
      rim tissue in the optic disc for both black and white Americans. However, the
      relationship between IOP and neural rim area was different in whites and blacks.

PMID- 7639653
TI  - Asymptomatic rhegmatogenous retinal detachments.
AB  - OBJECTIVE: To describe the clinical characteristics and risk of progression of
      asymptomatic rhegmatogenous retinal detachments. METHODS: We retrospectively
      reviewed the clinical records of 28 patients (31 eyes) with asymptomatic
      rhegmatogenous retinal detachments followed up without surgery for 0.5 to 12.1
      years (mean, 3.4 years). Tractional tears were present in six eyes and atrophic
      holes in 25 eyes. In five patients, the asymptomatic retinal detachment was noted
      when the patient presented with a symptomatic retinal detachment in the fellow
      eye. RESULTS: Twenty-nine of the 31 eyes remained asymptomatic without
      progression of the retinal detachment. Two eyes progressed to a symptomatic
      retinal detachment 2.25 and 3.3 years after the initial examination, underwent a
      successful scleral buckling procedure, and maintained 20/20 visual acuity.
      CONCLUSIONS: Observation can be considered a reasonable option in the treatment
      of patients with asymptomatic retinal detachments. Chart documentation of the
      risks and benefits of observation and instruction of the patient on self
      monitoring of the peripheral visual field are necessary in such patients.

PMID- 7639654
TI  - A comparison of driving in older subjects with and without age-related macular
      degeneration.
AB  - OBJECTIVE: To determine the effects of age and central vision loss on driving
      skills. METHODS: Ten subjects with age-related macular degeneration and average
      binocular visual acuity of 20/70, and 11 age-similar subjects with normal vision,
      were examined with a battery of cognitive and visual tests, an interactive
      driving simulator, and an on-road driving test. Data were collected on the
      frequency of real-world accidents and convictions for traffic violations.
      RESULTS: There were no significant differences between the two groups on any of
      the cognitive tests. The age-related macular degeneration group demonstrated
      poorer performance on the driving simulator, including delayed braking response
      times to stop signs, slower speeds, and more of both lane boundary crossings and
      simulator accidents. The age-related macular degeneration group also demonstrated
      poorer overall on-road test performance, including having significantly more
      points deducted for driving too slowly and for not maintaining proper lane
      position. However, these effects on the simulator and the on-road test did not
      translate into an increased risk of real-world accidents for the age-related
      macular degeneration group. Significantly more control subjects than patients
      with age-related macular degeneration were involved in self-reported accidents,
      and significantly more control subjects had state convictions for traffic
      violations. There was evidence of compensation in the age-related macular
      degeneration group in four major areas: (1) not driving in unfamiliar areas; (2)
      traveling at slow speeds; (3) self-restricting their nighttime driving, and (4)
      taking fewer risks while driving (eg, not changing lanes). There was also
      evidence of compensation in the older control group. CONCLUSIONS: Vision,
      simulator, and on-road test variables combined with subjective risk taking
      predicted self-reported real-world accidents in a logistic regression analysis.
      However, risk taking, rather than simulator or road-test performance, was the
      most significant predictor for both patients with age-related macular
      degeneration and the control group.

PMID- 7639652
TI  - Quantitative assessment of macular edema with optical coherence tomography.
AB  - OBJECTIVE: To evaluate optical coherence tomography, a new technique for high
      resolution cross-sectional imaging of the retina, for quantitative assessment of
      retinal thickness in patients with macular edema. DESIGN: Survey examination with
      optical coherence tomography of patients with macular edema. SETTING: Referral
      eye center. PATIENTS: Forty-nine patients with the clinical diagnosis of diabetes
      or diabetic retinopathy and 25 patients with macular edema secondary to retinal
      vein occlusion, uveitis, epiretinal membrane formation, or cataract extraction.
      MAIN OUTCOME MEASURES: Correlation of optical coherence tomograms with slit-lamp
      biomicroscopy, fluorescein angiography, and visual acuity. RESULTS: Optical
      coherence tomograms of cystoid macular edema closely corresponded to known
      histopathologic characteristics. Quantitative measurement of retinal thickness is
      possible because of the well-defined boundaries in optical reflectivity at the
      inner and outer margins of the neurosensory retina. Serial optical coherence
      tomographic examinations allowed tracking of both the longitudinal progression of
      macular thickening and the resolution of macular edema after laser
      photocoagulation. In patients with diabetic retinopathy, measurements of central
      macular thickness with optical coherence tomography correlated with visual
      acuity, and optical coherence tomography was more sensitive than slit-lamp
      biomicroscopy to small changes in retinal thickness. CONCLUSIONS: Optical
      coherence tomography appears useful for objectively monitoring retinal thickness
      with high resolution in patients with macular edema. It may eventually prove to
      be a sensitive diagnostic test for the early detection of macular thickening in
      patients with diabetic retinopathy.

PMID- 7639655
TI  - Anterior ischemic optic neuropathy secondary to interferon alfa.
AB  - OBJECTIVE: To report the occurrence of anterior ischemic optic neuropathy as a
      complication of treatment with interferon alfa and to consider the possible
      underlying mechanisms for this association. DESIGN: Description of the clinical
      findings in two patients with this condition. SETTING: A neuro-ophthalmology
      referral center. PATIENTS: Two patients, ages 40 and 51 years, undergoing
      treatment with interferon alfa for malignant neoplasms experienced sudden
      bilateral, sequential visual loss with disc-related field defects and segmental
      optic disc edema. INTERVENTIONS: Treatment with aspirin and prednisone in one
      patient. MAIN OUTCOME MEASURES: Visual acuity, color vision, Goldmann perimetry
      testing, and fundus photography. RESULTS: Visual loss was mild and generally
      nonprogressive. The interval between initiating treatment with interferon alfa
      and onset of anterior ischemic optic neuropathy was similar to that of interferon
      associated vascular retinopathy. CONCLUSION: Anterior ischemic optic neuropathy
      may complicate treatment with interferon alfa. The underlying pathogenesis is
      probably multifactorial.

PMID- 7639656
TI  - Painful oculomotor palsy caused by posterior-draining dural carotid cavernous
      fistulas.
AB  - BACKGROUND: Carotid cavernous fistulas cause conjunctival hyperemia and orbital
      soft-tissue swelling because of increased flow directed anteriorly in ophthalmic
      veins. Less well recognized is that when fistular flow is directed posteriorly,
      these congestive features will be absent and the diagnosis of the "white-eyed
      shunt" will be missed unless angiography is performed. METHODS: Two patients who
      had oculomotor nerve palsies caused by posteriorly draining dural carotid
      cavernous fistulas were studied, and the 28 previously described cases were
      reviewed. RESULTS: One patient had a chronic painful palsy of the sixth cranial
      nerve, and the other, a palsy of the third cranial nerve. Cerebral angiography
      disclosed the fistulas. The clinical and imaging features of these cases conform
      to those of the 28 previously reported white-eyed shunts. Angiographic features
      do not explain why some posterior-draining fistulas cause sixth-nerve palsies and
      others cause third- (or rarely, fourth-) nerve palsies. CONCLUSIONS: Dural
      carotid cavernous fistulas that drain primarily into the inferior petrosal sinus
      may cause painful oculomotor palsies that elude diagnosis because they lack
      congestive orbito-ocular features. Treatment by embolization leads to more rapid
      resolution of manifestations.

PMID- 7639657
TI  - Management of overfiltering and leaking blebs with autologous blood injection.
AB  - We describe our experience with intrableb autologous blood injection to manage
      over-filtering and leaking blebs. Autologous blood was injected into 12 thin
      cystic filtration blebs of 12 eyes. Indications for blood injection included
      symptomatic hypotony in five eyes, hypotony associated with bleb leakage in five
      eyes, and bleb leakage without hypotony in two eyes. Seven eyes (58.3%) were
      classified as successes and five eyes (41.7%) were classified as failures. The
      mean (+/- SD) follow-up was 6.8 +/- 2.6 months. Among the eyes classified as
      successes, a significant increase was noted in intraocular pressure and visual
      acuity by a mean (+/- SD) of 5.1 +/- 2.9 mm Hg and 5.3 +/- 2.1 lines,
      respectively. Bleb leakage resolved in four of seven eyes. The most common
      complication was hyphema formation. Injection of autologous blood into a
      filtration bleb is an alternative procedure for management of excessive
      filtration or bleb leakage in selected patients.

PMID- 7639658
TI  - Experimental globe rupture after excimer laser photorefractive keratectomy.
AB  - OBJECTIVE: To assess corneal weakening after photorefractive keratectomy.
      METHODS: Photorefractive keratectomy was performed in 16 human eye-bank eyes by
      means of a 193-nm excimer laser (range, 6 to 54 diopters [D]). Porcine eyes
      underwent either photorefractive keratectomy procedures (range, 30 to 93 D) with
      a 5-mm beam diameter or deep 5-mm plano disc ablations. Intraocular pressure was
      increased gradually with the use of nitrogen gas until the globe ruptured.
      RESULTS: Human eyes with less than 42 D of correction ruptured at the limbus or
      behind the insertions of the extraocular muscles. Two eyes showed initial leakage
      at the 42-D ablation site. Ablations greater than 46 D entered the anterior
      chamber during treatment. One porcine eye ruptured at the ablation site after a
      42-D treatment. Other eyes ruptured at the equator with treatments up to 78 D.
      CONCLUSION: Excimer laser photorefractive keratectomy does not weaken the cornea
      after degrees of ablation commonly used in the clinical setting.

PMID- 7639659
TI  - Efficacy of equator rings in an experimental rabbit study.
AB  - OBJECTIVE: To determine the efficacy of the equator ring in maintaining the
      circular contour of the capsule bag equator and transparency of the posterior
      capsule after crystalline lens extraction in 12 rabbit eyes. METHODS: After
      phacoemulsification through a 5-mm window made by continuous circular
      capsulorrhexis in the central anterior capsule, a flexible silicone ring (outer
      diameter, 11.0 mm; width, 1.5 mm; and thickness, 1.5 mm) was implanted in the
      capsule in seven rabbit eyes. A 13.0-mm Sinskey-style posterior chamber
      intraocular lens was then implanted inside the ring. Three other eyes received
      only equator rings, and two others received only intraocular lenses. Eyes were
      followed up for 3.5 +/- 1.4 months (mean +/- SD) before enucleation and
      evaluation by stereomicroscopy; they then underwent light microscopic
      examination. RESULTS: The two eyes that received only the intraocular lens had
      equatorial distortion and severe posterior capsule opacification. In nine (90%)
      of the 10 eyes that were implanted with the rings, the circular contour of the
      equator was preserved, and seven (70%) of these 10 eyes had transparent posterior
      capsules. CONCLUSION: Implantation of the equator ring effectively maintained the
      circular contour of the capsule bag equator and inhibited cells at the bag
      equator from proliferating toward the center of the posterior capsule in the
      rabbit.

PMID- 7639661
TI  - Evolution of a retinal hemorrhage in a patient with sickle cell-hemoglobin C
      disease.

PMID- 7639660
TI  - Selective loss of blue cones and rods in human retinal detachment.
AB  - OBJECTIVE: To determine if there are histopathologic changes in the outer retina
      that could explain the blue-yellow color confusion previously described following
      rhegmatogenous retinal detachment in humans. METHODS: Ten eyes with traumatic
      retinal detachments were studied. Eight of the eyes were removed from 2 1/2 to 11
      days following trauma. In the remaining two eyes, the retinas were successfully
      reattached. Enzyme histochemical studies for carbonic anhydrase and
      immunochemical studies for S antigen were performed to distinguish blue cones
      from red/green cones. RESULTS: With the 2 1/2- to 4-day-old detachments, nearly
      all of the carbonic anhydrase-negative (blue-sensitive) cones and many of the
      rods were seen to have signs of irreversible necrosis, including extreme swelling
      of the inner segments and mitochondria, loss of the outer segments, and pyknotic
      and displaced nuclei. In the 6- and 11-day-old detachments, almost all of the
      carbonic anhydrase-negative cones and many rods were missing. Blue cones were
      essentially absent from the reattached retinas, and there were only about half
      the normal number of rods. CONCLUSIONS: Rhegmatogenous retinal detachment results
      in rapid and almost total loss of the blue cones. Significant rod loss also
      occurs in this type of detachment but the red/green cones are comparatively
      resistant to damage. These findings could explain the observed blue-yellow color
      confusion in such patients. We discuss other clinical implications.

PMID- 7639662
TI  - Lightning-induced ocular injury.

PMID- 7639663
TI  - Meeting report of the American Ophthalmological Society, 131st year annual
      meeting, Hot Springs, Va, May 21-24, 1995.

PMID- 7639664
TI  - Ophthalmologists in the 'news'.

PMID- 7639665
TI  - Four-point fixation technique for sutured posterior chamber intraocular lenses.

PMID- 7639666
TI  - Grating acuity tests should not be used for social service purposes in
      preliterate children.

PMID- 7639667
TI  - Bilateral optic neuritis following herpes zoster ophthalmicus.

PMID- 7639668
TI  - Corneal edema due to Asclepias curassavica.

PMID- 7639669
TI  - Coats' disease as a cause of anterior chamber cholesterolosis.

PMID- 7639670
TI  - Large pigmented actinic keratosis of the eyelid.

PMID- 7639671
TI  - Kaposi's sarcoma of the bulbar conjunctiva as an initial clinical manifestation
      of acquired immunodeficiency syndrome.

PMID- 7639672
TI  - Clarification of the Archives' publication policy.

PMID- 7639673
TI  - A topical carbonic anhydrase inhibitor finally arrives.

PMID- 7639674
TI  - Interferon: friend or foe?

PMID- 7639675
TI  - Use of ethical criteria in medical decision making. Corneal transplantation.
AB  - OBJECTIVES: To determine for a defined procedure the prevalence of the use of 15
      criteria currently or historically relied on to select recipients of scarce
      medical resources, and to compare this use with the determinations of a report of
      the American Medical Association Council on Ethical and Judicial Affairs
      identifying many of these criteria as ethically appropriate or inappropriate for
      such use. DESIGN: Survey. PARTICIPANTS: All US members of a national cornea
      society were sent survey instruments. Approximately 63% (214/340) responded. MAIN
      OUTCOME MEASURES: Mean ratings on a scale of 1 to 5 (not important to very
      important) for each of the allocation criteria with regard to degree of influence
      on the decision to perform a corneal transplantation. RESULTS: Ethically
      appropriate criteria tended to receive high overall ratings, and inappropriate
      criteria, low ratings. Three ethically inappropriate criteria received relatively
      high ratings: previous use of resources, perceived obstacles to treatment, and
      contribution of patient to disease. High percentages of respondents applied
      ratings other than not important to all criteria deemed ethically inappropriate.
      CONCLUSIONS: Certain ethically inappropriate criteria may have been viewed as
      influencing graft survival and thus thought to have ethically appropriate
      aspects, mitigating to some degree the aforementioned three ratings. Nonetheless,
      the study supports the need for standard setting and educational efforts about
      criteria for the allocation of medical resources to ensure that ethically
      inappropriate criteria are consciously excluded from decision making and to
      stimulate discussion and raise consciousness regarding this important issue.

PMID- 7639676
TI  - One-year evaluation of excimer laser photorefractive keratectomy for myopia and
      myopic astigmatism. Melbourne Excimer Laser Group.
AB  - OBJECTIVE: To evaluate prospectively the efficacy and safety of excimer laser
      photorefractive keratectomy in the treatment of myopia and myopic astigmatism.
      METHODS: Up to 15 diopters (D) of myopia with or without astigmatism of less than
      6 D was treated with an excimer laser (VISX Twenty/Twenty). One hundred fifty
      procedures have been followed up for more than 12 months. RESULTS: Postoperative
      refractions were generally stable after 3 months without significant early
      overcorrection. Of those eyes treated with spherical equivalents of 5 D or less,
      96% were within 1 D of the targeted refraction after photorefractive keratectomy
      and 88% had uncorrected visual acuities of 20/40 or better. At 12 months, 77% of
      all 150 eyes treated achieved an uncorrected visual acuity of 20/40 or better and
      81% were within 1 D of the intended correction. Nine eyes (6%) lost 2 or more
      lines of best corrected visual acuity and 14 (9%) gained 2 or more lines. Adverse
      reactions were reported in 12 patients (8%) during the postoperative period.
      CONCLUSIONS: Photorefractive keratectomy is capable of correcting low and
      moderate myopic errors with a relatively high degree of accuracy and safety. The
      predictability and stability of the postoperative refraction during the first 12
      months seem to be good.

PMID- 7639677
TI  - Cloning and expression of cDNAs for the beta subunit of eukaryotic initiation
      factor-2B, the guanine nucleotide exchange factor for eukaryotic initiation
      factor-2.
AB  - A key control point in the initiation of protein synthesis in mammalian cells is
      the recycling of eukaryotic initiation factor (eIF)-2 by the guanine nucleotide
      exchange factor eIF-2B. In mammalian cells, eIF-2B is a complex of five different
      subunits termed epsilon, delta, gamma, beta and alpha. To clone cDNAs for the
      beta subunit of rabbit eIF-2B, amino acid sequence data was first obtained and
      used to design redundant oligonucleotide primers for use in PCR. PCR products
      were used to screen a rabbit liver cDNA library in lambda gt11 to obtain full
      length cDNAs for eIF-2B beta. The cDNAs were sequenced completely on both strands
      and revealed an open reading frame encoding a predicted 351-amino acid
      polypeptide of 39.0 kDa. The molecular mass and pI (5.99) of the predicted
      protein agree well with the properties of eIF-2B beta purified from rabbit
      reticulocytes. In vitro transcription/-translation of the cDNAs gave rise to a
      product that migrated at a position indistinguishable from that of this subunit
      of the purified protein. The amino acid sequence shows a high degree of
      similarity to that of GCD7, a Saccharomyces cerevisiae protein thought to be
      equivalent to mammalian eIF-2B beta. Northern-blot analysis revealed a single
      major mRNA species for eIF-2B beta in each of the four rabbit tissues tested.

PMID- 7639678
TI  - Proliferative and cytotoxic effects of mildly oxidized low-density lipoproteins
      on vascular smooth-muscle cells.
AB  - We have investigated the role of low-density lipoprotein (LDL) oxidation in the
      proliferative effect of LDLs on cultured bovine aortic smooth-muscle cells and
      compared it with their effect on bovine aortic endothelial cells. The following
      conclusions were reached. (1) Non-toxic doses of mildly oxidized LDLs elicit a
      proliferative effect on smooth-muscle cells significantly higher than that of
      native LDLs or lipoprotein-depleted serum. The proliferative effect is dependent
      on time (relatively slow), dose (high doses are cytotoxic) and the level of LDL
      oxidation. (2) The proliferative effect on smooth-muscle cells is counterbalanced
      at high concentrations of mildly oxidized LDLs (or at high oxidation levels) by
      their cytotoxic effect. (3) The same dose of mildly oxidized LDLs exhibits no
      proliferative effect on endothelial cells but rather a cytotoxic one. Endothelial
      cells may therefore be intrinsically more susceptible to the cytotoxic effect of
      mildly oxidized LDLs than are smooth-muscle cells. (4) The proliferative effect
      of native LDLs on smooth-muscle cells results (at least in part) from cell
      induced LDL oxidation during cell culture as suggested by (i) the progressive LDL
      oxidation over the 3 days of contact between LDLs and smooth-muscle cells and
      (ii) the concomitant inhibition of LDL oxidation and proliferative effect by
      butylated hydroxytoluene. The hypothetical mechanisms and potential involvement
      in atherogenesis are discussed.

PMID- 7639679
TI  - Aggretin, a novel platelet-aggregation inducer from snake (Calloselasma
      rhodostoma) venom, activates phospholipase C by acting as a glycoprotein Ia/IIa
      agonist.
AB  - A potent platelet aggregation inducer, aggretin, was purified from Malayan-pit
      viper (Calloselasma rhodostoma) venom by ionic-exchange chromatography, gel
      filtration chromatography and HPLC. It is a heterodimeric protein (29 kDa) devoid
      of esterase, phospholipase A and thrombin-like activity. Aggretin (> 5 nM)
      elicited platelet aggregation with a lag period in both human platelet-rich
      plasma and washed platelet suspension. EDTA (5 mM), prostaglandin E1 (1 microM)
      and 3,4,5-trimethoxybenzoic acid 8-(diethylamino)octyl ester ('TMB-8'; 100
      microM) abolished its aggregating activity, indicating that exogenous bivalent
      cations and intracellular Ca2+ mobilization are essential for aggretin-induced
      platelet aggregation. Neomycin (4 mM) and mepacrine (50 microM) completely
      inhibited aggretin (33 nM)-induced aggregation; however, creatine
      phosphate/creatine phosphokinase (5 mM, 5 units/ml) and indomethacin (50 microM)
      did not significantly affect its aggregating activity. Aggretin caused a
      significant increase of [3H]InsP formation in [3H]Ins-loaded platelets,
      intracellular Ca2+ mobilization and thromboxane B2 formation. Neomycin, a
      phospholipase C inhibitor, completely inhibited both the increase of [3H]InsP and
      intracellular Ca2+ mobilization of platelets stimulated by aggretin. A monoclonal
      antibody (6F1) directed against glycoprotein Ia/IIa inhibited platelet shape
      change and aggregation induced by aggretin. 125I-aggretin bound to platelets with
      a high affinity (Kd = 4.0 +/- 1.1 nM), and the number of binding sites was
      estimated to be 2119 +/- 203 per platelet. It is concluded that aggretin may act
      as a glycoprotein Ia/IIa agonist to elicit platelet aggregation through the
      activation of endogenous phospholipase C, leading to hydrolysis of
      phosphoinositides and subsequent intracellular Ca2+ mobilization.

PMID- 7639680
TI  - Enoyl-acyl-carrier-protein reductase and Mycobacterium tuberculosis InhA do not
      conserve the Tyr-Xaa-Xaa-Xaa-Lys motif in mammalian 11 beta- and 17 beta
      hydroxysteroid dehydrogenases and Drosophila alcohol dehydrogenase.

PMID- 7639682
TI  - The regulatory protein of glucokinase binds to the hepatocyte matrix, but, unlike
      glucokinase, does not translocate during substrate stimulation.
AB  - The kinetic properties of hepatic glucokinase (hexokinase IV) are modulated by
      binding to a regulatory protein. This study shows that, in hepatocytes incubated
      with 5 mM glucose as sole carbohydrate substrate, both glucokinase and its
      regulatory protein bind to the cell matrix by a Mg(2+)-dependent mechanism. After
      incubation with an elevated [glucose] or with fructose, glucokinase, but not its
      regulatory protein, translocates from the Mg(2+)-dependent binding site. It is
      suggested that the regulatory protein acts as a receptor for anchoring
      glucokinase to the hepatocyte matrix and inhibiting its activity in metabolically
      quiescent conditions.

PMID- 7639681
TI  - Control of adipocyte differentiation.

PMID- 7639683
TI  - The cloning and sequence of the C isoform of PtdIns4P 5-kinase.
AB  - In this study we describe the purification and sequencing of the C isoform of
      platelet PtdIns4P 5-kinase. Subsequently a cDNA was isolated from a human
      circulating-leucocyte library, which when sequenced was shown to contain all of
      the peptides identified in the purified protein. In addition, expression of this
      cDNA in bacteria led to the production of a protein which was recognized by
      specific monoclonal antibodies raised to the bovine brain enzyme [Brooksbank,
      Hutchings, Butcher, Irvine and Divecha (1993) Biochem. J. 291, 77-82] and also
      led to the appearance of PtdIns4P 5-kinase activity in the bacterial lysates.
      Interestingly, the cDNA showed no similarity to any of the previously cloned
      inositide kinases. A search of the DNA databases showed that two proteins from
      Saccharomyces cerevisiae shared close similarity to this enzyme, one of which,
      the mss4 gene product, has been implicated in the yeast inositol lipid pathway.
      These data suggest that the PtdIns4P 5-kinases are a new family of inositide
      kinases unrelated to the previously cloned phosphoinositide 3/4-kinases.

PMID- 7639684
TI  - Retinoic acid directly stimulates osteoclastic bone resorption and gene
      expression of cathepsin K/OC-2.
AB  - Vitamin A metabolites such as all-trans-retinoic acid (all-trans-RA) affect
      several steps of metabolic processes in vertebrates. In the last few years,
      several studies have shown the effect of RA on bone formation and metabolism.
      However, mechanisms of its action still remain unclear, especially with respect
      to the regulation of bone cells. Therefore, this study was carried out to clarify
      how RA regulates the activity of osteoclasts. Using a pit assay involving
      unfractionated bone cells, including osteoclasts obtained from rabbits, we found
      that RA stimulated an increase in the bone-resorbing activity in a dose- and time
      dependent manner. Furthermore, this effect occurred more rapidly than that of
      treatments with 1 alpha,25-dihydroxyvitamin D3. However, this effect of RA may be
      partly related to cross-talk between osteoclasts and other types of cells.
      Therefore we studied the effect of RA on isolated osteoclasts. We found that all
      trans-RA regulates the gene expression of cathepsin K/OC-2, a dominant cysteine
      proteinase, at the transcriptional level in mature osteoclasts isolated from
      rabbits. Moreover, retinoic acid-receptor alpha mRNA and retinoid X-receptor beta
      mRNA were expressed in these mature osteoclasts. Our results indicate that
      osteoclasts are target cells for RA and that RA might regulate a part of bone
      formation and metabolism through osteoclasts.

PMID- 7639685
TI  - Primaquine, an inhibitor of vesicular transport, blocks the calcium-release
      activated current in rat megakaryocytes.
AB  - The whole-cell patch-clamp technique was used to study the effect of primaquine,
      an inhibitor of vesicular transport, on the calcium-release-activated current
      (Icrac) in rat megakaryocytes. Addition of primaquine, before emptying of
      internal Ca2+ stores by ionomycin, prevented the development of Icrac, with a
      half-maximal concentration of near 100 microM. Maximal inhibition (> or = 83%)
      was observed at 0.6-1 mM primaquine. At 1 mM, chloroquine, a related compound
      which is less effective at blocking vesicular secretion, had no effect on Icrac.
      Primaquine (0.8 mM) added after sustained activation of Icrac caused a gradual
      block of current, with maximal inhibition of 50% observed after 2-3 min. At 1 mM,
      internal guanosine 5'-[gamma-thio]triphosphate reduced Icrac by 65 +/- 13%.
      Neither 1 mM GTP nor 2 mM guanosine 5'-[beta-thio]diphosphate had any significant
      effect on Icrac. The recognized role of GTPases in the regulation of vesicular
      trafficking, together with block of Icrac activation by primaquine, provide
      evidence that the channels carrying Icrac may be stored in a vesicular membrane
      compartment and transferred to the plasma membrane following store depletion.

PMID- 7639686
TI  - Dissection of stress-activated glucose transport from insulin-induced glucose
      transport in mammalian cells using wortmannin and ML-9.
AB  - The signaling pathways responsible for the activation of glucose transport by
      insulin and by metabolic stress in mammalian cells were studied in Clone 9 cells
      and 3T3-L1 adipocytes. Exposure of both cell types to azide or insulin markedly
      increased their glucose uptake capacity (Vmax.) without affecting their apparent
      affinity for glucose (Km). The effects of azide and insulin were not additive.
      Wortmannin, a selective inhibitor of phosphatidylinositol (PI) 3-kinase, did not
      affect stimulation of transport by azide but inhibited insulin-induced glucose
      transport with a Ki of < 10 nM. ML-9, a putative mitogen-activated protein kinase
      inhibitor, was equipotent in its inhibition of azide- and insulin-stimulated
      glucose transport. These findings suggest that multiple signalling cascades are
      involved in the stimulation of glucose transport in mammalian cells and that PI 3
      kinase, an essential link in the pathway by which insulin stimulates glucose
      transport, is not necessary for the activation of glucose uptake by metabolic
      stress.

PMID- 7639687
TI  - Fate of soluble methionine in African trypanosomes: effects of metabolic
      inhibitors.
AB  - The metabolism of [35S]methionine in cultured bloodstream forms of African
      trypanosomes was followed using flow-through radiodetection linked to liquid
      chromatography separation. The effects of a transmethylase inhibitor, sinefungin,
      and of the ornithine decarboxylase inhibitor, DL-alpha-difluoromethylornithine
      (Ornidyl; DFMO), on methionine metabolism were also observed. Trypanosomes
      rapidly incorporated [35S]methionine into S-adenosylmethionine (AdoMet) and the
      metabolites methylthioadenosine, S-adenosylhomocysteine, homocysteine,
      cystathionine cysteine and glutathione. Untreated trypanosomes excreted large
      quantities of cystathionine and cysteine into the growth medium. DFMO-treated
      cells formed larger quantities of AdoMet more rapidly than did control cells, as
      was evident from initial time points (30 min and 1 h). Decarboxylated AdoMet,
      present in trace quantities in control cells, accumulated in DFMO-treated cells.
      Sinefungin increased the AdoMet concentrations approximately 20-fold over that of
      controls after a 6 h incubation with [35S]methionine, while cystathionine and
      cysteine levels decreased. The half-life (t1/2) and rate of turnover of AdoMet
      were measured in cells treated with DFMO or sinefungin. DFMO treatment caused a
      substantial increase in the rate of AdoMet utilization, while sinefungin extended
      the t1/2 and lowered AdoMet turnover. These studies show that trypanosomes
      rapidly metabolize methionine through AdoMet to intermediates of the polyamine
      and transmethylation pathways. Agents inhibiting these pathways rapidly affect
      the concentration and rate of utilization of AdoMet, significantly changing the
      concentrations of metabolites.

PMID- 7639688
TI  - Characterization and partial purification of a ferrireductase from human duodenal
      microvillus membranes.
AB  - Reduction of ferric iron in the presence of HuTu 80 cells or duodenal microvillus
      membranes (MVMs) was investigated. With both systems, NADH-dependent reduction of
      Fe3+/NTA (nitrilotriacetic acid) was demonstrated, using the ferrous iron
      chelator ferrozine. Uptake of Fe3+ from Fe3+/NTA by HuTu 80 cells was strongly
      inhibited by addition of ferrozine, indicating that Fe2+ is the substrate for the
      iron uptake system. With isolated plasma membranes it is shown that the reductase
      activity is sensitive to trypsin and incubation at 65 degrees C. The reductase
      activity could be extracted from the plasma membrane and partially purified by
      ammonium sulphate precipitation and isoelectric focusing. From the purification
      and inhibition characteristics we conclude that reduction of ferric iron on the
      surface of duodenal plasma membranes is catalysed by a membrane protein.

PMID- 7639689
TI  - The non-catalytic cellulose-binding domain of a novel cellulase from Pseudomonas
      fluorescens subsp. cellulosa is important for the efficient hydrolysis of Avicel.
AB  - A genomic library of Pseudomonas fluorescens subsp. cellulosa DNA, constructed in
      lambda ZAPII, was screened for carboxymethyl-cellulase activity. The pseudomonad
      insert from a recombinant phage which displayed elevated cellulase activity in
      comparison with other cellulase-positive clones present in the library, was
      excised into pBluescript SK- to generate the plasmid pC48. The nucleotide
      sequence of the cellulase gene, designated celE, revealed a single open reading
      frame of 1710 bp that encoded a polypeptide, defined as endoglucanase E (CelE),
      of M(r) 59663. The deduced primary structure of CelE revealed an N-terminal
      signal peptide followed by a 300-amino-acid sequence that exhibited significant
      identity with the catalytic domains of cellulases belonging to glycosyl hydrolase
      Family 5. Adjacent to the catalytic domain was a 40-residue region that exhibited
      strong sequence identity to non-catalytic domains located in two other
      endoglucanases and a xylanase from P. fluorescens. The C-terminal 100 residues of
      CelE were similar to Type-I cellulose-binding domains (CBDs). The three domains
      of the cellulase were joined by linker sequences rich in serine residues.
      Analysis of the biochemical properties of full-length and truncated derivatives
      of CelE confirmed that the enzyme comprised an N-terminal catalytic domain and a
      C-terminal CBD. Analysis of purified CelE revealed that the enzyme had an M(r) of
      56000 and an experimentally determined N-terminal sequence identical to residues
      40-54 of the deduced primary structure of full-length CelE. The enzyme exhibited
      an endo mode of action in hydrolysing a range of cellulosic substrates including
      Avicel and acid-swollen cellulose, but did not attack xylan or any other
      hemicelluloses. A truncated form of the enzyme, which lacked the C-terminal CBD,
      displayed the same activity as full-length CelE against soluble cellulose and
      acid-swollen cellulose, but exhibited substantially lower activity than the full
      length cellulase against Avicel. The significance of these data in relation to
      the role of the CBD is discussed.

PMID- 7639690
TI  - Mutation in aspartic acid residues modifies catalytic and haemolytic activities
      of Bacillus cereus sphingomyelinase.
AB  - Four aspartic acid residues (Asp126, Asp156, Asp233 and Asp295) of Bacillus
      cereus sphingomyelinase (SMase) in the conservative regions were changed to
      glycine by in vitro mutagenesis, and the mutant SMases [D126G (Asp126-->Gly
      etc.), D156G, D233G and D295G] were produced in Bacillus brevis 47, a protein
      producing strain. The sphingomyelin (SM)-hydrolysing activity of D295G was
      completely abolished and those of D126G and D156G were reduced by more than 80%,
      whereas that of D233G was not so profoundly affected. Two mutant enzymes (D126G
      and D156G) were purified and characterized further. The hydrolytic activities of
      D126G and D156G toward four phosphocholine-containing substrates with different
      hydrophobicities, SM, 2-hexadecanoylamino-4-nitrophenylphosphocholine(HNP),
      lysophosphatidylcholine (lysoPC) and p-nitro-phenylphosphocholine (p-NPPC), were
      compared with those of the wild-type. The activity of D126G toward water-soluble
      p-NPPC was comparable with that of the wild-type. On the other hand, D156G
      catalysed the hydrolysis of hydrophilic substrates such as HNP and p-NPPC more
      efficiently (> 4-fold) than the wild-type. These results suggested that Asp126
      and Asp156, located in the highly conserved region, may well be involved in a
      substrate recognition process rather than catalytic action. Haemolytic activities
      of the mutant enzymes were found to be parallel with their SM-hydrolysing
      activities. Two regions, including the C-terminal region containing Asp295, were
      found to show considerable sequence identity with the corresponding regions of
      bovine pancreatic DNase I. Structural predictions indicated structural similarity
      between SMase and DNase I. An evolutionary relationship based on the catalytic
      function was suggested between the structures of these two phosphodiesterases.

PMID- 7639691
TI  - Evidence for the location of a binding sequence for the alpha 2 beta 1 integrin
      of endothelial cells, in the beta 1 subunit of laminin.
AB  - To date no specific location on laminin 1 for the binding of alpha 2 beta 1
      integrin has been described, although recent evidence supports a location in the
      E1XNd fragment of the cross region. We have identified a peptide sequence from
      this region, in the beta 1 chain of laminin 1, YGYYGDALR, which inhibits the
      adhesion of endothelial cells to laminin 1 and type-IV collagen. A structurally
      related sequence from the CNBr-cleaved fragment CB3 of the alpha 1 chain of
      collagen type IV, FYFDLR, inhibits endothelial cell adhesion to both collagen
      types I and IV and laminin 1. The CB3 fragment containing the FYFDLR sequence has
      been shown to contain binding sites for both alpha 1 beta 1 and alpha 2 beta 1
      integrins. Present experiments with anti-integrin antibodies indicate that the
      alpha 2 beta 1 integrin on endothelial cells can account for all the cell binding
      to collagen types I and IV, and that this integrin makes a major contribution
      towards the adhesion of these cells to laminin 1. We therefore propose that the
      peptide FYFDLR participates in alpha 2 beta 1 binding to collagen type IV and
      that the putatively structurally similar peptide, YGYYGDALR, participates in
      alpha 2 beta 1 binding to laminin 1. This is the first account of structurally
      related peptide sequences from laminin 1 and type-IV collagen which show
      reciprocal inhibition of cell adhesion to either ligand and which might form part
      of a common integrin-binding site, as well as the first suggestion of a precise
      location contributing to the alpha 2 beta 1 integrin binding site on laminin 1.

PMID- 7639692
TI  - Sequence variation of a novel heptahelical leucocyte receptor through alternative
      transcript formation.
AB  - Chemoattractants, including chemokines such as interleukin 8 (IL-8) and related
      proteins, activate leucocytes via seven-transmembrane-domain G-protein-coupled
      receptors. A cDNA for a novel receptor of this kind consisting of 327 amino acids
      was isolated from a human blood monocyte cDNA library. The polypeptide, termed
      monocyte-derived receptor 15 (MDR15), is an alternative form of the Burkitt's
      lymphoma receptor 1 (BLR1) encoded by a human Burkitt's lymphoma cDNA [Dobner,
      Wolf, Emrich and Lipp (1992) Eur. J. Immunol. 22, 2795-2799]. MDR15 and BLR1
      cDNAs differ in the 5' region, where the open reading frame of MDR15 is shorter
      by 45 codons. Southern-blot analysis indicates that the two transcripts for MDR15
      and BLR1 are encoded by the same gene. Northern-blot analysis using a probe that
      hybridizes with both mRNAs demonstrated high-level expression in chronic B
      lymphoid leukaemia and non-Hodgkin's lymphoma cells and, to a lesser extent,
      peripheral blood monocytes and lymphocytes. Reverse transcription-PCR studies
      with MDR15- and BLR1-specific primers showed similar levels of transcripts for
      both receptors in RNA that was positive in Northern-blot analysis. MDR15 and BLR1
      have high structural similarity to receptors for human IL-8 (about 40% amino acid
      identity) and other chemokines. However, none of a series of radiolabelled
      chemokines (IL-8, NAP-2, GRO alpha, PF4, IP10, MCP-1, MCP-2, MCP-3, I-309, RANTES
      and MIP-1 alpha) and other ligands (C3a and leukotriene B4) bound to Jurkat
      transfectants that stably expressed either MDR15 or BLR1 mRNA. The fact that
      MDR15 and BLR1 are expressed on leucocytes and show marked sequence similarity to
      chemokine receptors suggests the existence of as yet unidentified chemokines.
      Alternative transcript formation affecting the 5'-terminal part of the coding
      region may be a way to modify ligand-binding selectivity.

PMID- 7639694
TI  - The structure of polyamine analogues determines haemoglobin production and
      cytotoxicity in murine erythroleukaemia cells.
AB  - The naturally occurring polyamine spermine induces haemoglobin synthesis in
      murine erythroleukaemia (MEL) cells. We have studied the ability of various
      polyamine analogues to inhibit cell growth and induce haemoglobin production.
      Polyamine analogues with free terminal amino groups were good inducers of
      haemoglobin production in MEL cells. Haemoglobin levels correlated with the
      number of positive charges: pentamines (five positive charges) were stronger
      inducers than tetramines (four positive charges). Compounds ethylated at their
      terminal amines were poor inducers of haemoglobin production but good inhibitors
      of MEL cell growth. These results provide evidence that polyamine analogues
      support specific biological functions of polyamines in MEL cells and suggest
      relationships between polyamine structure and function.

PMID- 7639693
TI  - Spermine induces haemoglobin synthesis in murine erythroleukaemia cells.
AB  - The naturally occurring polyamine spermine induces haemoglobin synthesis in
      murine erythroleukaemia (MEL) cells. Haemoglobin production was accompanied by
      accumulation of cytoplasmic beta-globin mRNA and growth inhibition, but not by
      cell-cycle block or changes in cell volume. Hexamethylene-bisacetamide (HMBA), a
      well known differentiating agent, also induces haemoglobin production, but causes
      a G1 block and decreases cell volume. These findings indicate that HMBA and
      spermine affect MEL cells differently, even though both induce haemoglobin
      production.

PMID- 7639695
TI  - Octopus S-crystallins with endogenous glutathione S-transferase (GST) activity:
      sequence comparison and evolutionary relationships with authentic GST enzymes.
AB  - S-Crystallin is a major protein present in the lenses of cephalopods (octopus and
      squid). To facilitate the cloning of this crystallin gene, cDNA was constructed
      from the poly(A)+ mRNA of octopus lenses, and amplified by PCR for nucleotide
      sequencing. Sequencing of 10 of 15 positive clones coding for this crystallin
      revealed three distinct S-crystallin isoforms with 61-64% identity in nucleotide
      sequences and 42-58% similarity in amino acid sequences when compared with
      homologous crystallins in squid lenses. These charge-isomeric crystallins also
      show between 26 and 33% amino acid sequence identity to four major classes of
      glutathione S-transferase (GST), a major detoxification enzyme present in most
      mammalian tissues. For further analysis, expression of one of the S-crystallin
      cDNAs was carried out in the bacterial expression system pQE-30, and the S
      crystallin protein produced in Escherichia coli was purified to homogeneity to
      determine the enzymic properties. We found that the expressed octopus S
      crystallin possessed much lower GST activity than the authentic GSTs from other
      tissues. Sequence comparison and construction of phylogenetic trees for S
      crystallins from squid and octopus lenses and various classes of GSTs revealed
      that S-crystallins represent a multigene family which is structurally related to
      Alpha-class GSTs and probably derived from the ancestral GST by gene duplication
      and subsequent multiple mutational substitutions.

PMID- 7639696
TI  - Distinct populations of high-M(r) mucins secreted by different human salivary
      glands discriminated by density-gradient electrophoresis.
AB  - High-M(r) mucins [mucin glycoprotein 1 (MG1)] isolated from human saliva from the
      individual salivary glands were chemically characterized. The carbohydrate
      content of MG1 derived from palatal (PAL), submandibular (SM) and sublingual (SL)
      saliva was typical of mucins but showed heterogeneity, especially in the amount
      of sialic acid and sulphated sugar residues. The physicochemical properties of
      native MG1s make conventional SDS/PAGE and ion-exchange chromatography unsuitable
      for investigating differences between individual samples. Recently a density
      gradient electrophoresis (DGE) device has been developed, primarily for
      separation based on the charge of entire cells or cell organelles [Tulp, Verwoerd
      and Pieters (1993) Electrophoresis 14, 1295-1301]. We have used this apparatus to
      study the high-M(r) salivary mucins. Using DGE, the MG1s of individual glands
      were seen to have clearly distinct electrophoretic mobilities, as monitored by
      ELISA using MG1-specific monoclonal antibodies. Even within a particular MG1
      preparation, subpopulations could be distinguished. DGE analysis of a chemically
      and enzymically modified MG1 series, followed by ELISA and dot-blot detection
      using specific monoclonal antibodies, lectins and high-iron diamine staining,
      suggests that the high electrophoretic mobility of PAL-MG1 is mainly the result
      of a high sulphate content, whereas the SL subpopulations differ mainly in
      binding type and amount of sialic acid. SM-MG1 most resembles the low-mobility
      subpopulation of SL-MG1, except that it has a lower sulphate content. In
      conclusion, DGE appears to be a powerful method for analysis of native mucin; it
      has been used to demonstrate that MG1s from the various salivary glands are
      biochemically much more diverse than was previously assumed.

PMID- 7639697
TI  - Epoxidation of plasmalogens: source for long-chain alpha-hydroxyaldehydes in
      subcellular fractions of bovine liver.
AB  - 1. Masked long-chain alpha-hydroxyaldehydes were trapped in all subcellular
      fractions of bovine liver by application of pentafluorbenzyloxime derivatization
      [van Kuijk, Thomas, Stephens and Dratz (1986) Biochem. Biophys. Res. Commun. 139,
      144-149] and quantified via GLC/MS using characteristic ion traces. 2. The chain
      length profile of long-chain 2-hydroxyalkanales clearly indicates their
      relationship to plasmalogens as precursor molecules. 3. The previously postulated
      existence of alpha-acyloxyplasmalogens as precursor molecules of masked long
      chain alpha-hydroxyaldehydes in bovine tissue lipids [Lutz and Spiteller (1991)
      Liebigs Ann. Chem. 1991, 563-567] was excluded. 4. The constant oxidation rate of
      plasmalogens in all subcellular fractions provides conclusive evidence for a non
      enzymic plasmalogen epoxidation process (probably via hydroperoxy radicals). 5.
      The high reactivity of alpha-hydroxyaldehydes sheds some doubt on the postulation
      that plasmalogens protect mammalian cells against oxidative stress as postulated
      previously [Morand, Zoeller and Raetz (1988) J. Biol. Chem. 263, 11590-11596;
      Morand, Zoeller and Raetz (1988) J. Biol. Chem. 263, 11597-11606].

PMID- 7639698
TI  - Association of a RING finger protein with the cytoplasmic domain of the human
      type-2 tumour necrosis factor receptor.
AB  - A human gene encoding a protein that specifically binds to the intracellular
      domain of the 75 kDa type-2 tumour necrosis factor (TNF) receptor (TNFR-2IC) has
      been identified using the yeast-based two-hybrid system. The N-terminal half of
      the TNF receptor-associated protein (TRAP) contains RING finger and zinc finger
      motifs often found in DNA-binding proteins including transcription factors. The
      2.4 kb TRAP mRNA was barely detectable, if present at all, in lung, and variably
      expressed in heart, liver, placenta, brain, skeletal muscle, kidney and the
      pancreas; interestingly, the TRAP was more highly expressed in transformed cell
      lines than in normal tissues. This observation may be consistent with a role for
      this TRAP in promoting or regulating cellular proliferation. After in vitro
      transcription/translation and 35S labelling the TRAP was precipitated using a
      fusion protein consisting of glutathione S-transferase and the intracellular
      domain of TNFR-2 (TNFR-2IC), which showed that the two proteins directly interact
      in a mammalian cell-free system and also that identification of the TRAP was not
      an artifact of the two-hybrid system. By using truncated TNFR-2ICs for in vitro
      precipitation of 35S-TRAP, it was shown that the C-terminal half of the TNFR-2IC
      contains the domain necessary for interaction with TRAP. The TRAP identified in
      the present study shares considerable homology with, and may be the human
      homologue of, a mouse protein, TNF receptor-associated factor 2 (TRAF2), that
      binds mouse TNFR-2.

PMID- 7639699
TI  - Isolation and characterization of the androgen-dependent mouse cysteine-rich
      secretory protein-3 (CRISP-3) gene.
AB  - The mRNA for cysteine-rich secretory protein-3 (CRISP-3) was originally
      identified in the mouse salivary gland as an androgen-dependent transcript, and
      is closely related to CRISP-1 and CRISP-2 which are abundantly expressed in the
      epididymis and testis respectively. Overlapping phage clones encompassing the
      entire length of the CRISP-3 gene were isolated from a lambda EMBL3 genomic
      library and analysed. DNA sequencing revealed that the gene consisted of eight
      exons ranging between 55 and 740 bp in size, and seven introns. All exon-intron
      junctions conformed to the GT/AG rule established for eukaryotic genes. The
      length of the introns was determined by PCR and was found to vary between 1.0 and
      3.7 kb, indicating that the gene spans over 20 kb of the mouse genome. Primer
      extension allowed the mapping of the major transcription initiation site to an
      adenine located at the appropriate position downstream of a bona fide TATA box,
      in a region corresponding well to the eukaryotic consensus sequence. Over 800 bp
      of CRISP-3 promoter region were determined and two regions almost exactly
      matching the androgen-responsive element consensus RGWACANNNTGTWCY detected. In
      addition, sequences described in the Drosophila melanogaster Sgs-3 gene as being
      involved in its salivary gland-specific expression as well as two putative OTF-
      and GATA-binding elements were also found.

PMID- 7639700
TI  - Molecular cloning of an orphan G-protein-coupled receptor that constitutively
      activates adenylate cyclase.
AB  - A human gene encoding an orphan G-protein-coupled receptor named ACCA (adenylate
      cyclase constitutive activator) was isolated from a genomic library using as a
      probe a DNA fragment obtained by low-stringency PCR. Human ACCA (hACCA) is a
      protein of 330 amino acids that exhibits all the structural hallmarks of the main
      family of G-protein-coupled receptors. Expression of hACCA resulted in a dramatic
      stimulation of adenylate cyclase, similar in amplitude to that obtained with
      other Gs-coupled receptors fully activated by their respective ligands. This
      stimulation was obtained in a large variety of stable cell lines derived from
      various organs, and originating from different mammalian species. hACCA was found
      to be the human homologue of a recently reported mouse orphan receptor (GPCR21).
      The mouse ACCA (mACCA) was therefore recloned by PCR, and expression of mACCA in
      Cos-7 cells demonstrated that the mouse receptor behaved similarly as a
      constitutive activator of adenylate cyclase. It is not known presently whether
      the stimulation of adenylate cyclase is the result of a true constitutive
      activity of the receptor or, alternatively, is the consequence of a permanent
      stimulation by a ubiquitous ligand. The tissue distribution of mACCA was
      determined by RNase protection assay. Abundant transcripts were found in the
      brain, whereas lower amounts were detected in testis, ovary and eye. Various
      hypotheses concerning the constitutive activity of ACCA and their potential
      biological significance are discussed.

PMID- 7639701
TI  - Regulation of skeletal-muscle AMP deaminase: involvement of histidine residues in
      the pH-dependent inhibition of the rabbit enzyme by ATP.
AB  - Reaction of rabbit skeletal-muscle AMP deaminase with a low molar excess of
      diethyl pyrocarbonate results in conversion of the enzyme into a species with one
      or two carbethoxylated histidine residues per subunit that retains sensitivity to
      ATP at pH 7.1 but, unlike the native enzyme, it is not sensitive to regulation by
      ATP at pH 6.5. This effect mimics that exerted on the enzyme by limited
      proteolysis with trypsin, which removes the 95-residue N-terminal region from the
      80 kDa enzyme subunit. These observations suggest involvement of some histidine
      residues localized in the region HHEMQAHILH (residues 51-60) in the regulatory
      mechanism which stabilizes the binding of ATP to its inhibitory site at acidic
      pH. Carbethoxylation of two histidine residues per subunit abolishes the
      inhibition by ATP of the proteolysed enzyme at pH 7.1, suggesting the obligatory
      participation of a second class of histidine residues, localized in the 70 kDa
      subunit core, in the mechanism of the pH-dependent inhibition of the enzyme by
      ATP. At a slightly acidic pH, these histidine residues would be positively
      charged, resulting in a desensitized form of the enzyme similar to that obtained
      with the carbethoxylation reaction.

PMID- 7639702
TI  - Purification and properties of the lipoate protein ligase of Escherichia coli.
AB  - Lipoate is an essential component of the 2-oxoacid dehydrogenase complexes and
      the glycine-cleavage system of Escherichia coli. It is attached to specific
      lysine residues in the lipoyl domains of the E2p (lipoate acetyltransferase)
      subunit of the pyruvate dehydrogenase complex by a Mg(2+)- and ATP-dependent
      lipoate protein ligase (LPL). LPL was purified from wild-type E. coli, where its
      abundance is extremely low (< 10 molecules per cell) and from a genetically
      amplified source. The purified enzyme is a monomeric protein (M(r) 38,000) which
      forms irregular clusters of needle-like crystals. It is stable at -20 degrees C,
      but slowly oxidizes to an inactive form containing at least one intramolecular
      disulphide bond at 4 degrees C. The inactive form could be re-activated by
      reducing agents or by an as-yet unidentified component (reactivation factor)
      which is resolved from LPL at the final stage of purification. The pI is 5.80,
      and the Km values for ATP, Mg2+ and DL-lipoate were determined. Selenolipoate and
      6-thio-octanoate were alternative but poorer substrates. Lipoylation was
      reversibly inhibited by the 6- and 8-seleno-octanoates and 8-thio-octanoate,
      which reacted with the six cysteine thiol groups of LPL. LPL was inactivated by
      Cu2+ ions in a process that involved the formation of inter- and intra-molecular
      disulphide bonds. Studies with lplA mutants lacking LPL activity indicated that
      E. coli possesses another distinct lipoylation system, although no such activity
      could be detected in vitro.

PMID- 7639703
TI  - Identification and characterization of a functional retinoic acid/thyroid hormone
      response element upstream of the human insulin gene enhancer.
AB  - A deletion analysis of the human insulin gene extending to 2 kb upstream of the
      transcription start site provided evidence of regulatory sequences located
      upstream of the insulin-linked polymorphic region (ILPR). Within this ILPR-distal
      region is a sequence (Ink, for insulin kilobase upstream) which contains three
      potential nuclear hormone-receptor half-sites, closely matching the consensus
      sequence AGGTCA. These sequences are arranged as a palindromic element with zero
      spacing over-lapping a direct repeat with 2 bp spacing. The Ink sequence was used
      in electrophoretic mobility-shift assays within nuclear extracts from COS-7 cells
      overexpressing the vitamin D, thyroid hormone or retinoic acid receptors, or from
      an insulin-expressing hamster cell line, HIT-T15. These studies suggest that the
      insulin-expressing cell line contains thyroid hormone and retinoic acid receptors
      at least, and that these receptors are able to recognize the Ink sequence. Three
      copies of the Ink sequence were placed upstream of the thymidine kinase promoter
      and firefly luciferase reporter gene. In COS-7 cells expressing the appropriate
      nuclear hormone receptor, this construct was responsive to both thyroid hormone
      (18-fold) and all-trans-retinoic acid (31-fold). In HIT-T15 cells the same
      construct responded to all-trans-retinoic acid, but not to thyroid hormone.
      Within the context of a 2 kb insulin gene fragment, the Ink sequence was shown to
      be activated by retinoic acid and by the retinoic acid receptor, but acted as a
      negative element in the presence of both retinoic acid and the retinoic acid
      receptor. Mutagenesis studies demonstrated that the palindromic sequence was
      important for the retinoic acid response, and for binding of complexes containing
      retinoic acid receptor. In human islets of Langerhans, retinoic acid was shown to
      stimulate insulin mRNA levels. These results demonstrate that a functional
      nuclear hormone-receptor-response element is located upstream of the human ILPR.
      As retinoic acid and thyroid hormone are frequently involved in developmental
      regulatory processes, it is possible that this element may be important in the
      process of islet cell differentiation.

PMID- 7639704
TI  - The modulation of phosphatidylinositol biosynthesis in hamster hearts by methyl
      lidocaine.
AB  - Methyl lidocaine is an experimental anti-arrhythmic drug which has been shown to
      enhance the biosynthesis of phosphatidyl-inositol (PI) in the hamster heart. In
      this study, the effect of methyl lidocaine on enzymes involved in the
      biosynthesis of PI in the heart was examined. When the hamster heart was perfused
      with labelled methyl lidocaine, the majority of the compound was not metabolized
      after perfusion. The direct action of methyl lidocaine on an enzyme was studied
      by the presence of the drug in enzyme assays, whereas its indirect action was
      studied by assaying the enzyme activity in the heart after methyl lidocaine
      perfusion. CTP:phosphatidic acid cytidylyl-transferase, a rate-limiting enzyme in
      PI biosynthesis, was stimulated by methyl lidocaine in a direct manner. Kinetic
      studies revealed that methyl lidocaine caused a change in the affinity between
      the enzyme and phosphatidic acid and resulted in the enhancement of the reaction.
      Alternatively, acyl-CoA:lysophosphatidic acid acyltransferase, another key enzyme
      for PI biosynthesis, was not activated by the presence of methyl lidocaine.
      However, the enzyme activity was stimulated in hearts perfused with methyl
      lidocaine. The enhancement of the acyl-transferase by methyl lidocaine perfusion
      was found to be mediated via the adenylate cyclase cascade with the elevation of
      the cyclic AMP level. The stimulation of protein kinase A activity by cyclic AMP
      resulted in the phosphorylation and activation of the acyltransferase.
      Interestingly, the activity of protein kinase C was not stimulated by methyl
      lidocaine perfusion. We conclude that the enhancement of PI biosynthesis by
      methyl lidocaine in the hamster heart resulted from the direct activation of the
      cytidylyltransferase, as well as the phosphorylation and subsequent activation of
      the acyltransferase.

PMID- 7639705
TI  - The hydrophobic mannoside Man alpha 1-6Man alpha 1-S-(CH2)7-CH3 acts as an
      acceptor for the UDP-Gal:glycosylphosphatidylinositol anchor alpha 1,3
      galactosyltransferase of Trypanosoma brucei.
AB  - The variant surface glycoproteins (VSGs) of Trypanosoma brucei are attached to
      the plasma membrane via a glycosylphosphatidylinositol (GPI) membrane anchor.
      This anchor contains the core sequence ethanolamine-PO4-6Man alpha 1-2Man alpha 1
      6Man alpha 1-4GlcN alpha 1-6myo-inositol, which is conserved in all GPI anchors,
      and a unique alpha Gal side chain attached to the 3-position of the alpha Man
      residue adjacent to the alpha GlcN residue. Here we report that trypanosome
      membranes can catalyse the transfer of Gal from UDP-Gal to the hydrophobic
      thioglycoside Man alpha 1-6Man alpha 1-S-(CH2)7-CH3. Characterization of the
      galactosylated products by electrospray mass spectrometry, exoglycosidase
      digestion and periodate-oxidation studies revealed that the major product was Man
      alpha 1-6(Gal alpha 1-3)Man alpha 1-S-(CH2)7-CH3. The similarity of this product
      to part of the mature VSG GPI anchor suggests that the thioglycoside is able to
      act as an acceptor for the trypanosome-specific UDP-Gal-GPI anchor alpha 1,3
      galactosyltransferase.

PMID- 7639706
TI  - Reduction of ubiquinone in membrane lipids by rat liver cytosol and its
      involvement in the cellular defence system against lipid peroxidation.
AB  - Rat liver homogenates reduced ubiquinone (UQ)-10 to ubiquinol (UQH2)-10 in the
      presence of NADPH rather than NADH. This NADPH-dependent UQ reductase (NADPH-UQ
      reductase) activity that was not inhibited by antimycin A and rotenone, was
      located mainly in the cytosol fraction and its activity accounted for 68% of that
      of the homogenates. Furthermore, the NADPH-UQ reductase from rat liver cytosol
      efficiently reduced both UQ-10 incorporated into egg yolk lecithin liposomes, and
      native UQ-9 residing in rat microsomes, to the respective UQH2 form in the
      presence of NADPH. The gross redox ratios of UQH2-9/(UQ-9 + UQH2-9) in individual
      tissues of rat correlated positively with the log of their respective cytosolic
      NADPH-UQ reductase activities, while the redox ratios in every intracellular
      fraction from liver were at about the same level, irrespective of NADPH-UQ
      reductase activities in the respective fractions. The combined addition of rat
      liver cytosol and NADPH inhibited to a great extent 2,2'-azobis(2,4-dimethyl
      valeronitrile)-induced lipid peroxidation of UQ-10-fortified lecithin liposomes
      and completely inhibited such peroxidation in the liposomes in which UQH2-10
      replaced UQ-10. The NADPH-UQ reductase activity was clearly separated from DT
      diaphorase (EC 1.6.99.2) activity by means of Cibacron Blue-immobilized Bio-Gel A
      5m chromatography. In conclusion, the NADPH-UQ reductase in cytosol, which is a
      novel enzyme to our knowledge, was presumed to be responsible for maintaining the
      steady-state redox levels of intracellular UQ and thereby to act as an endogenous
      antioxidant in protecting intracellular membranes from lipid peroxidation that is
      inevitably induced in aerobic metabolism.

PMID- 7639707
TI  - Oxygen free radicals enhance the nitric oxide-induced covalent NAD(+)-linkage to
      neuronal glyceraldehyde-3-phosphate dehydrogenase.
AB  - Nitric oxide (NO) induces a covalent modification of glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH) from various tissues. This phenomenon, which has previously
      been interpreted as an auto-ADP-ribosylation, is in fact a covalent binding of
      NAD+ to the enzyme. In the present study, we show that 3-morpholino-sydnonimine
      (SIN-1) is much more efficient than sodium nitroprusside (SNP) in stimulating the
      covalent labelling of GAPDH from cultured striatal neurones in the presence of
      [adenylate-32P]NAD+ (877 +/- 110 and 266 +/- 33% increase in NAD(+)-labelling
      induced by maximally effective concentrations of SIN-1 and SNP respectively). The
      difference in the efficacy of both NO-generating compounds could be due to the
      additional release of superoxide by SIN-1, since superoxide dismutase and the
      nitrone 5,5'-dimethyl pyrroline-1-oxide markedly inhibited the SIN-1-induced
      covalent binding of NAD+ to GAPDH. Catalase and selective scavengers of hydroxyl
      radicals, mannitol and dimethyl sulphoxide, did not alter the SIN-1-induced
      covalent modification of GAPDH, ruling out the involvement of hydroxyl radicals
      in this phenomenon. Supporting further a role of oxygen free radicals in the NAD+
      linkage to GAPDH, pyrogallol, a superoxide generator, which alone was
      ineffective, potentiated the SNP-evoked response. The NAD+ linkage to neuronal
      GAPDH measured in the presence of NO and superoxide probably involves sulphydryl
      groups, since the radiolabelling of the protein was reversed by exposure to HgCl2
      and prevented by pretreatment with the alkylating agent N-ethylmaleimide.
      Moreover, the NO-induced inhibition of GAPDH activity was enhanced by pyrogallol,
      which was ineffective alone. In conclusion, the present study indicates that
      superoxide anions potentiate NO-induced covalent NAD(+)-linkage to GAPDH and
      enzyme inactivation.

PMID- 7639708
TI  - The binding of animal low-density lipoproteins to human apolipoprotein(a).
AB  - Lipoprotein(a) [Lp(a)] is a risk factor for coronary artery disease. It is
      composed of lipids and apolipoprotein(a) [apo(a)] linked to apolipoprotein B
      (apoB) by a disulphide bond between Cys-4057 of apo(a)'s kringle 36 and possibly
      Cys-3734 of apoB. We call this the covalent apo(a): apoB-Lp interaction, to
      distinguish it from the non-covalent apo(a)/Lp(a): apoB-Lp interaction, which is
      probably mediated by apo(a)'s kringle 33 and residues 3304-3317 of apoB. The non
      covalent interaction could be the initial interaction which brings apo(a) and
      apoB together prior to covalent linkage and Lp(a) formation. The non-covalent
      apo(a)/Lp(a)-binding site on apoB is evolutionarily more ancient than the
      covalent apo(a)-binding site on apoB. Both human and non-human low-density
      lipoproteins (LDLs) bind non-covalently to human apo(a)/Lp(a); however, only
      rabbit and human LDLs bind covalently to human apo(a). The non-covalent
      interaction between mouse LDL and human apo(a)/Lp(a) has a Kd of (1.7 +/- 1.33) x
      10(-7) M (n = 3). This explains the co-localization of human apo(a) and mouse
      apoB in the atherosclerotic lesions of human apo(a) transgenic mice and supports
      our hypothesis that the non-covalent interaction is a contributing factor to
      apo(a) atherogenicity.

PMID- 7639709
TI  - Fluorescent, short-chain C6-NBD-sphingomyelin, but not C6-NBD-glucosylceramide,
      is subject to extensive degradation in the plasma membrane: implications for
      signal transduction related to cell differentiation.
AB  - The involvement of the plasma membrane in the metabolism of the sphingolipids
      sphingomyelin (SM) and glucosylceramide (GlcCer) was studied, employing
      fluorescent short-chain analogues of these lipids, 6-[N-(7-nitro-2,1,3
      benzoxadiazol-4-yl) amino]hexanoylsphingosylphosphorylcholine (C6-NBD-SM), C6-NBD
      GlcCer and their common biosynthetic precursor C6-NBD-ceramide (C6-NBD-Cer).
      Although these fluorescent short-chain analogues are metabolically active, some
      caution is to be taken in view of potential changes in biophysical/biochemical
      properties of the lipid compared with its natural counterpart. However, these
      short-chain analogues offer the advantage of studying the lipid metabolic enzymes
      in their natural environment, since detergent solubilization is not necessary for
      measuring their activity. These studies were carried out with several cell types,
      including two phenotypes (differing in state of differentiation) of HT29 cells.
      Degradation and biosynthesis of C6-NBD-SM and C6-NBD-GlcCer were determined in
      intact cells, in their isolated plasma membranes, and in plasma membranes
      isolated from rat liver tissue. C6-NBD-SM was found to be subject to extensive
      degradation in the plasma membrane, due to neutral sphingomyelinase (N-SMase)
      activity. The extent of C6-NBD-SM hydrolysis showed a general cell-type
      dependence and turned out to be dependent on the state of cell differentiation,
      as revealed for HT29 cells. In undifferentiated HT29 cells N-SMase activity was
      at least threefold higher than in its differentiated counterpart. In contrast, in
      all cell types studied, very little if any biosynthesis of C6-NBD-SM from the
      precursor C6-NBD-Cer occurred. Moreover, in the case of C6-NBD-GlcCer, neither
      hydrolytic nor synthetic activity was found to be associated with the plasma
      membrane. These results are discussed in the context of the involvement of the
      sphingolipids SM and GlcCer in signal transduction pathways in the plasma
      membrane.

PMID- 7639710
TI  - Regulation of phosphoenolpyruvate carboxykinase gene transcription by thyroid
      hormone involves two distinct binding sites in the promoter.
AB  - Transcription of the gene for phosphoenolpyruvate carboxy-kinase (PEPCK) is
      stimulated by thyroid hormone (T3), glucagon (via cyclic AMP) and
      glucocorticoids. A region of the PEPCK promoter between -332 and -308 mediates
      the induction of transcription by T3. To characterize this region further,
      mutations were introduced into this region of the PEPCK promoter and the modified
      promoters ligated to the chloramphenicol acetyltransferase (CAT) reporter gene.
      Using these PEPCK-CAT vectors in transient transfections in HepG2 cells, it was
      found that T3 stimulates PEPCK transcription through two direct repeats of the
      AGGTCA motif located between nucleotides -330 and -319 [PEPCK-thyroid-hormone
      responsive element (TRE)]. The beta form of the T3 receptor (TR beta) bound PEPCK
      TRE as a homodimer but bound far more efficiently as a heterodimeric complex with
      the retinoid X receptor (RXR). An additional region called P3(I) (-250 to -234)
      is required for T3 responsiveness and binds members of the CCAAT-enhancer-binding
      protein (C/EBP) family. P3(I) contains an AGGTCA-like motif that can bind the TR
      beta-RXR heterodimer. Mutagenesis of this motif abolished TR beta-RXR binding
      without reducing T3 induction. Mutation of the C/EBP-binding site or insertion of
      a cyclic AMP-responsive-binding-protein site at P3(I) eliminated the T3 response.
      Our results indicate that T3 stimulation of PEPCK transcription is mediated by TR
      beta bound to PEPCK-TRE and requires C/EBP to be bound at the P3(I) site.

PMID- 7639711
TI  - Cloning of the cDNA encoding mast cell tryptase of Mongolian gerbil, Meriones
      unguiculatus, and its preferential expression in the intestinal mucosa.
AB  - By using the combination of reverse-transcription PCR and rapid amplification of
      cDNA ends methods, a cDNA encoding mast cell tryptase was successfully cloned
      from the small intestine of Mongolian gerbil, Meriones unguiculatus, infected
      with Nippostrongylus brasiliensis. The cDNA was 1219 bp long including 810 bp of
      an open reading frame. Based on the deduced amino acid sequences of known mast
      cell tryptases of other species, the gerbil mast cell tryptase (gMCT) was highly
      similar to mouse mast cell protease (mMCP)-7, and seems to be translated as a
      prepro-enzyme with 25 amino acids of signal and activation peptides and 245 amino
      acids of mature enzyme. The gMCT mRNA was preferentially transcribed in the
      intestinal mucosa and to a far lesser extent in the connective tissue such as
      skin and tongue. Moreover, kinetic study after infection revealed that the amount
      of gMCT mRNA in the small intestine correlated well with the degree of intestinal
      mastocytosis. Throughout the course of infection, enzyme-histochemically
      detectable tryptase activity was limited to mucosal mast cells. Since mucosal
      mast cells of other rodents, including mice and rats, do not express tryptases,
      this is the first report of rodent mast cell tryptase expressed in the intestinal
      mucosa.

PMID- 7639712
TI  - The design of peptide-based substrates for the cdc2 protein kinase.
AB  - The substrate sequence specificity of the cdc2 protein kinase from Pisaster
      ochraceus has been evaluated. The peptide, Ac-Ser-Pro-Gly-Arg-Arg-Arg-Arg-Lys
      amide, serves as an efficient cdc2 kinase substrate with a Km of 1.50 +/- 0.04
      microM and a Vmax. of 12.00 +/- 0.18 mumol/min per mg. The amino acid sequence of
      this peptide is not based on any sequence in a known protein substrate of the
      cyclin-dependent kinase, but rather was designed from structural attributes that
      appear to be important in the majority of cdc2 substrates. The cyclin-dependent
      enzyme is remarkably indiscriminate in its ability to recognize and phosphorylate
      peptides that contain an assortment of structurally diverse residues at the P-2,
      P-1 and P+2 positions. However, peptides that contain a free N-terminal serine or
      lack an arginine at the P+4 position are relatively poor substrates. These
      aspects of the substrate specificity of the cdc2 protein kinase are compared and
      contrasted with the previously reported substrate specificity of a cdc2-like
      protein kinase from bovine brain [Beaudette, Lew and Wang (1993) J. Biol. Chem.
      268, 20825-20830].

PMID- 7639713
TI  - Lysophospholipids activate ovarian and breast cancer cells.
AB  - We have investigated the effects of phospholipids on activation and proliferation
      of ovarian and breast cancer cells. Lysophosphatidic acid (LPA),
      lysophosphatidylserine (LPS) and sphingosylphosphorylcholine (SPC) all induce
      transient increases in cytosolic free Ca2+ ([Ca2+]i) in both ovarian and breast
      cancer cell lines. The ability of LPA, LPS and SPC to induce increases in [Ca2+]i
      in ovarian and breast cancer cells is likely to be due to an interaction with
      cell-surface receptors as the increases in [Ca2+]i were: (1) due to release of
      calcium from intracellular stores and not from transmembrane uptake due to
      changes in permeability; (2) blocked by lanthanum and suramin which do not enter
      cells; (3) blocked by phorbol esters which interrupt increases in [Ca2+]i induced
      through a number of different receptors; and (4) not detected in freshly isolated
      peripheral blood mononuclear cells, indicating cell type specificity. In
      addition, increases in [Ca2+]i induced by LPA, LPS and SPC in ovarian and breast
      cancer cells completely self-desensitized and cross-desensitized each other, but
      did not block increases in [Ca2+]i induced by thrombin. Lysophosphatidylglycerol
      (LPG), but not other lysophospholipids, inhibited LPA- but not LPS- or SPC
      induced increases in [Ca2+]i, suggesting that LPA may interact with a different
      receptor(s) to LPS or SPC and that their downstream signalling pathways converge
      or interact. LPA, SPC and LPS also induced rapid increases in tyrosine
      phosphorylation of specific cellular proteins, including p125FAK. Strikingly,
      LPA, but not LPS or SPC, induced activation of mitogen-activated protein (MAP)
      kinases. Despite an ability to activate similar intracellular signaling events,
      LPA, LPS and SPC exhibited markedly different effects on cell proliferation.
      Whereas LPA induced a significant increase in cell proliferation, LPS did not
      substantially alter cell proliferation and SPC inhibited cell proliferation.
      Surprisingly, phosphatidic acid (PA), which did not induce increases in [Ca2+]i,
      p125FAK activation or activation of MAP kinases, did induce proliferation of
      ovarian cancer cells, albeit at higher concentrations that LPA. The discordance
      between sensitivity to LPG, early biochemical events stimulated, and the eventual
      proliferation response combine to suggest that LPA probably utilizes a different
      receptor from LPS, SPC and PA. Therefore ovarian and breast cancer cells are
      sensitive to the effects of a number of different phospholipids which may play a
      role in the growth of these tumour cells in the cancer patient and are thus
      potential targets for therapy.

PMID- 7639714
TI  - The phosphorylation state of the microtubule-associated protein tau as affected
      by glutamate, colchicine and beta-amyloid in primary rat cortical neuronal
      cultures.
AB  - The effects of the excitatory amino acid glutamate, the microtubule destabilizing
      agent colchicine, and beta 25-35-amyloid peptide on the phosphorylation state of
      tau were studied in rat cortical neurons in primary culture. Using
      immunocytochemistry and Western-blot analysis, we demonstrated that a proportion
      of tau in these cultures is normally highly phosphorylated, but most of this tau
      fraction is dephosphorylated after treatment of the cultures with glutamate or
      colchicine, but not with beta-amyloid; the glutamate- and colchicine-induced
      changes in tau phosphorylation commenced before cell death, as assessed by
      release of lactate dehydrogenase. Dephosphorylation of tau was readily revealed
      by using the monoclonal antibodies Tau.1 and AT8, which have phosphate-sensitive
      epitopes that both centre around serine-199 and -202 (numbering of the largest
      tau isoform). On Western blots and by immunocytochemistry, AT8 labelling strongly
      decreased after glutamate and colchicine treatments, whereas Tau.1 staining was
      more intense. Neurofilament monoclonal antibodies, including RT97, 8D8, SMI31 and
      SMI310, all additionally known to recognize tau in a phosphorylation-dependent
      manner, also demonstrated that glutamate and colchicine treatments of the
      cultures induced a dephosphorylation of tau. We also showed immunocytochemically
      that there is an increase in tau immunoreactivity in neuronal perikarya in
      response to glutamate and colchicine treatment, and this occurs concomitantly
      with the dephosphorylation of tau. Treatment of the primary rat cortical neuronal
      cultures with beta 25-35-amyloid peptide, under conditions which induce neuronal
      degeneration, did not induce a change in tau phosphorylation, and failed to act
      synergistically with glutamate to produce an increase in dephosphorylation of tau
      over that produced by glutamate treatment alone. These findings demonstrate that
      glutamate and colchicine induce tau dephosphorylation, as opposed to increased
      tau phosphorylation, which would be more indicative of Alzheimer-type
      neurodegeneration.

PMID- 7639715
TI  - Alignment of caldesmon on the actin-tropomyosin filaments.
AB  - We have reported previously that each smooth-muscle caldesmon binds predominantly
      to a region within residues 142-227 of tropomyosin, but a weaker binding site
      also exists at the N-terminal region of tropomyosin [Watson, Kuhn, Novy, Lin and
      Mak (1990) J. Biol. Chem. 265, 18860-18866]. In view of recent evidence for the
      presence of tropomyosin-binding sites at both the N- and C-terminal domains of
      caldesmon, we have studied the binding of the N- and C-terminal fragments of
      human fibroblast caldesmon expressed in Escherichia coli to tropomyosin and its
      CNBr fragments. The N-terminal fragment, CaD40 (residues 1-152), binds
      tropomyosin, but the interaction is mostly abolished in the presence of actin.
      CaD40 binds strongly to Cn1B(142-281) of tropomyosin, but weakly to Cn1A(11-127).
      The C-terminal fragment, CaD39, which corresponds to residues 443-736 of gizzard
      caldesmon, binds tropomyosin, and the interaction is enhanced by actin. CaD39
      binds to both Cn1A(11-127) and Cn1B(142-281) of tropomyosin. Our results suggest
      that the N-terminal domain of caldesmon interacts with the C-terminal half of one
      tropomyosin molecule, whereas the C-terminal domain binds to both N- and C
      terminal regions of the adjacent tropomyosin molecule along the actin filament.
      In addition, the binding of the N-terminal domain of caldesmon to the actin
      tropomyosin filament is weak, which may allow this domain to project off the thin
      filament to interact with myosin.

PMID- 7639716
TI  - Expression of cell-surface proteoglycan mRNA by human articular chondrocytes.
AB  - The expression of six cell-surface proteoglycans (syndecan, fibroglycan,
      amphiglycan, glypican, betaglycan and CD44) was studied at the mRNA level.
      Analysis was performed by Northern blotting using total RNA preparations from
      freshly isolated articular chondrocytes obtained from both juveniles and adults.
      Similar results were obtained for both age groups. By far the most abundant
      message was that for amphiglycan, CD44 message was next in relative abundance,
      and the messages for fibroglycan, glypican and betaglycan were all expressed at
      low levels. Syndecan message could not be detected by this technique. This
      pattern of expression was different to that observed in cultured skin
      fibroblasts, where the messages for amphiglycan, CD44, fibroglycan and glypican
      were all expressed at a similar level. In contrast with the fibroblasts, where
      the amphiglycan message exhibits no size polymorphism, the chondrocyte
      amphiglycan message is present in three polymorphic forms, due to the use of
      alternative polyadenylation signals. When the newly isolated chondrocytes are
      maintained in monolayer culture for several passages, the amphiglycan message
      heterogeneity reverts to that characteristic of the fibroblasts. Thus human
      articular chondrocytes are characterized by both their high level of amphiglycan
      message expression and their use of alternative polyadenylation signals.

PMID- 7639717
TI  - Arg-27, Arg-127 and Arg-155 in the beta-trefoil protein barley alpha
      amylase/subtilisin inhibitor are interface residues in the complex with barley
      alpha-amylase 2.
AB  - Arginine residues in barley alpha-amylase/subtilisin inhibitor (BASI) involved in
      binding to barely alpha-amylase 2 (AMY2) were differentially labelled using AMY2
      as protectant and phenylglyoxal (PGO) and [14C]PGO as modifying agents.
      Chymotryptic fragments of labelled BASI were purified by reverse-phase HPLC, and
      we concluded that the radiolabelled Arg-27, Arg-155 and most likely Arg-127,
      identified by amino acid, sequence and 14C analyses, are protected by AMY2. While
      Arg-106 and Arg-107 showed intermediate reactivity and apparently were only
      partly accessible, Arg-15, Arg-41 and Arg-61 reacted with PGO and were thus
      exposed in the BASI-AMY2 complex. Patterns of arginine modification by [14C]PGO
      in free or in AMY2-complexed BASI were consistent with the results of
      differential labelling. The AMY2-protected arginines in BASI are at a distance
      from each other, as deduced from crystal structures of different beta-trefoil
      proteins (Erythrina caffra and soybean trypsin inhibitors, interleukin-1 alpha
      and -1 beta and WASI, the wheat homologue), suggesting that the BASI-AMY2 complex
      has multiple contacts at a larger interface. Accordingly, 11-16-residue-long BASI
      oligopeptides synthesized to include Arg-27, Arg-106/Arg-107 or Arg-127 were
      unable to suppress the formation of BASI-AMY2 or the effect of an inhibitory
      monoclonal antibody to BASI. Since Arg-27 is not conserved in rice and wheat
      ASIs, we further propose that Arg-155 in BASI is the kinetically identified PGO
      sensitive group that is essential for inhibition [Abe, Sidenius and Svensson
      (1993) Biochem. J. 293, 151-155].

PMID- 7639718
TI  - Bound plasminogen is rate-limiting for cell-surface-mediated activation of
      plasminogen by urokinase.
AB  - The ability of U937 monocyte-like cells and KATO III cells (a human gastric
      carcinoma line) to potentiate activation of plasminogen by single-chain urokinase
      type plasminogen activator (scu-PA), as mediated by the cell receptor for
      urokinase (u-PAR), was compared. It was observed that, although the concentration
      of u-PAR on these cell lines differed considerably (U937 cells: 5000
      receptors/cell, Kd 0.35 nM; KATO III cells: 400 receptors/cell, Kd 0.85 nM), the
      rate of activation of plasminogen by scu-PA in the presence of the same density
      of each cell line was equivalent. From data generated in the presence of
      increasing concentrations of scu-PA, the kcat, for plasminogen activation in the
      presence of each cell line was calculated and found to differ by 26-fold (0.36 s
      1 on U937 cells; 9.25 s-1 on KATO III cells). However, the Km for plasminogen
      with respect to the rate of formation of plasmin was lower than the Kd for
      binding (0.2 microM compared with 0.5 microM on U937 cells; 0.34 microM compared
      with 1.6 microM on KATO III cells). A rapid transformation from Glu-plasminogen
      (native plasminogen with N-terminal Glu) to Lys-plasminogen (plasmin-degraded
      plasminogen with primarily N-terminal Lys-77) occurred on the surface of U937
      cells (unlike KATO III cells), but this transition did not coincide with faster
      rates of plasminogen activation. From this evidence it is concluded that the
      accessibility of bound plasminogen acts to limit the rate of activation by cell
      bound urokinase. The significance of this proposal is that the proteolytic
      potential of the cell-mediated activation of plasminogen would be controlled by
      the accessibility of plasminogen for activation rather than by the concentration
      of u-PAR (the latter may act to localize proteolysis to appropriate domains on
      the surface of the cell).

PMID- 7639719
TI  - The napEDABC gene cluster encoding the periplasmic nitrate reductase system of
      Thiosphaera pantotropha.
AB  - The napEDABC locus coding for the periplasmic nitrate reductase of Thiosphaera
      pantotropha has been cloned and sequenced. The large and small subunits of the
      enzyme are coded by napA and napB. The sequence of NapA indicates that this
      protein binds the GMP-conjugated form of the molybdopterin cofactor. Cysteine-181
      is proposed to ligate the molybdenum atom. It is inferred that the active site of
      the periplasmic nitrate reductase is structurally related to those of the
      molybdenum-dependent formate dehydrogenases and bacterial assimilatory nitrate
      reductases, but is distinct from that of the membrane-bound respiratory nitrate
      reductases. A four-cysteine motif at the N-terminus of NapA binds a [4Fe-4S]
      cluster. The DNA- and protein-derived primary sequence of NapB confirm that this
      protein is a dihaem c-type cytochrome and, together with spectroscopic data,
      indicate that both NapB haems have bis-histidine ligation. napC is predicted to
      code for a membrane-anchored tetrahaem c-type cytochrome that shows sequence
      similarity to the NirT cytochrome c family. NapC may be the direct electron donor
      to the NapAB complex. napD is predicted to encode a soluble cytoplasmic protein
      and napE a monotopic integral membrane protein, napDABC genes can be discerned at
      the aeg-46.5 locus of Escherichia coli K-12, suggesting that this operon encodes
      a periplasmic nitrate reductase system, while napD and napC are identified
      adjacent to the napAB genes of Alcaligenes eutrophus H16.

PMID- 7639720
TI  - Immunochemical characterization of L-isoaspartyl-protein carboxyl
      methyltransferase from mammalian tissues.
AB  - Polyclonal antibodies were raised against a synthetic peptide corresponding to a
      sequence of 14 amino acid residues found near the C-terminus of L-isoaspartyl (D
      aspartyl)-protein carboxyl methyltransferase (PCMT). The affinity-purified
      antibodies were used to detect the methyltransferase by Western-blot analysis in
      cytosolic and membrane fractions from several mammalian tissues. A protein of 27
      kDa was detected in the cytosol of most tissues; co-incubation with the peptide
      used for immunization abolished the detection. The identity of the 27 kDa protein
      as a PCMT was demonstrated by renaturation of PCMT activity from
      SDS/polyacrylamide gels. The methyltransferase from brain cytosol was
      immunoprecipitated by the anti-PCMT antibodies and Protein A-agarose, indicating
      that the native protein was recognized by the antibodies. PCMT was also
      immunodetected in crude membranes from brain, testes and heart, and in purified
      membranes from kidney cortex. The expression of the methyltransferase was higher
      in bovine and human brain than in rat tissues. The bovine enzyme had a greater
      electrophoretic mobility, suggesting small structural differences. The membrane
      bound methyltransferase could be extracted with detergents above their critical
      micellar concentration, but not with salt, alkaline or urea solutions suggesting
      that the binding of the enzyme to membranes is hydrophobic by nature. Anti-PCMT
      antibodies provide an interesting tool for studies regarding the expression of
      these enzymes in both soluble and membrane fractions of various cell types.

PMID- 7639721
TI  - The biosynthesis of threonine by mammalian cells: expression of a complete
      bacterial biosynthetic pathway in an animal cell.
AB  - The coding regions for the Escherichia coli gene for aspartokinase I/homoserine
      dehydrogenase I (thrA) and the Corynebacterium glutamicum gene for aspartic
      semialdehyde dehydrogenase (asd) have been subcloned into a Simian Virus 40
      (SV40)-based mammalian expression vector. Both enzyme activities are expressed in
      mouse 3T3 cells after transfer of the corresponding chimaeric gene. The kinetic
      parameters are similar to those of the native bacterial enzymes, and
      aspartokinase I/homoserine dehydrogenase I retains its allosteric regulation by
      threonine. An extract of the cells expressing aspartokinase I/homoserine
      dehydrogenase I, mixed with one from cells expressing aspartic semialdehyde
      dehydrogenase, produced homoserine when the mixture was incubated with aspartic
      acid, ATP and NADPH. The thrA and asd expression cassettes were combined into a
      single plasmid which, when transfected into 3T3 cells, enabled them to produce
      homoserine from aspartic acid. Homoserine-producing 3T3 cells were transfected
      with the plasmid pSVthrB/C (homoserine kinase and threonine synthase) and
      selected for growth on homoserine. Cell lines isolated from these cells expressed
      the complete bacterial threonine pathway, were independent of threonine for
      growth and could be maintained in medium which contained no free threonine. The
      threonine in the proteins of these cells became enriched in 15N when the culture
      medium contained [15N]aspartic acid. The production of homoserine and the growth
      of cells was at a maximum when there was more than 2.5 mM aspartate in the
      medium. Below this concentration the high Km of aspartokinase limited the flux
      through the pathway. In the presence of additional aspartic acid the new pathway
      could sustain a cell cycle time close to that of the same cells cultured in
      threonine-containing medium.

PMID- 7639722
TI  - Heat shock factor-1 and the heat shock cognate 70 protein associate in high
      molecular weight complexes in the cytoplasm of NIH-3T3 cells.
AB  - Interaction of heat shock transcription factor-1 (HSF-1) with the seventy
      kilodalton heat shock cognate protein (HSC70) was examined in NIH 3T3 cells. HSF
      1 was found in the cytoplasm of non-stressed cells associated with HSC70 in large
      (Mr 400-500,000) complexes. After heat shock, HSF-1 became concentrated in the
      nucleus in smaller, more stable complexes that did not contain HSC70, an
      indication of significant rearrangement within the complexes. These experiments
      show a profound effect of heat shock on the structure and stability of HSF-1
      complexes during nuclear localization and support the hypothesis that HSC70
      binding may control HSF-1 function.

PMID- 7639723
TI  - Phenol sulfotransferase activities and localization in human nasal polyp
      epithelium.
AB  - Nasal polyp epithelia, which exhibit a wide variation in epithelial cell
      morphologies, were tested for phenol sulfotransferase (PST) enzymes.
      Immunohistology revealed little or no detectable PST antigen in normal ciliated
      pseudostratified epithelia or in simple squamous metaplastic epithelia; however,
      intense expression was observed in regions of non-ciliated epithelial cell
      hyperplasia and in squamous epithelial cells overlying such hyperplastic sites.
      Western blots confirmed the presence of both P-PST (32 kDa) and M-PST (34 kDa) in
      the tissue extracts. Bimodal distribution of PST activity as a function of 4
      nitrophenol concentration was consistent with expression of these two PST
      isoforms. These results indicate dynamic and epithelial differentiation-dependent
      expression of human PSTs in the nasal mucosa and suggest that these
      sulfotransferases can be modulated within human airways in vivo.

PMID- 7639724
TI  - Characterization of nuclear retinoic acid binding activity in sensitive leukemic
      cell lines: cell specific uptake of ATRA and RAR alpha protein modulation.
AB  - The diverse effects of all-trans retinoic acid (ATRA) on growth, differentiation
      and homeostasis of vertebrate organisms are mediated by three distinct isoforms
      of retinoic acid receptors (RARs). Although it is not known to what extent each
      RAR contributes to the different effects of ATRA, several studies have
      demonstrated that ATRA induced granulocytic differentiation in human myeloid
      leukemic cell lines is mediated by RAR alpha. In this study, we investigated ATRA
      binding affinity of the endogenous nuclear receptors of HL-60 and NB4 leukemic
      cells. Scatchard plot analysis yielded an apparent dissociation constant of 5 +/-
      0.3 nM and 1400 +/- 80 receptor sites per cell in HL-60 cells, whereas the NB4
      promyelocytic leukemic cell line showed a lower affinity (8.5 +/- 0.5 nM and 900
      +/- 30 receptor sites per cell). Modulation of RAR alpha protein (5 fold excess)
      was found in NB4 cells after 24 hours ATRA exposure, whereas HL-60 cells required
      a 72-hour culture period to weakly increase the RAR alpha protein level. These
      data were closely related to the ATRA intracellular concentration and kinetics of
      terminal differentiation of the cells.

PMID- 7639725
TI  - Rapid aldosterone signaling in vascular smooth muscle cells: involvement of
      phospholipase C, diacylglycerol and protein kinase C alpha.
AB  - Rapid in vitro effects of aldosterone (ALDO) on intracellular sodium, potassium
      and calcium, cell volume and the sodium-proton-antiport have been described in
      human mononuclear leukocytes and rat vascular smooth muscle cells (VSMC). These
      nongenomic effects are signaled through membrane receptors with a high affinity
      for aldosterone, but not for hydrocortisone. Effects of ALDO on the production of
      diacylglycerol (DAG) and protein kinase C alpha (PKC) were measured in VSCM by
      enzymatic assay and immunoblotting. DAG production was stimulated twofold by ALDO
      (> or = 1 nM) within 30 sec while hydrocortisone was inactive at concentrations
      of up to 1 microM. The inhibitors of phospholipase C, neomycin and U-73122
      completely blocked this effect. PKC translocation from cytosol to membranes by
      ALDO occurred within 5 min, the extent of this effect was comparable to that of
      angiotensin II. These data demonstrate rapid intracellular signaling for ALDO in
      VSMC through phospholipase C, DAG and PKC in addition to calcium and inositol
      1,4,5-trisphosphate as determined earlier.

PMID- 7639726
TI  - Stable production of mutant mice from double gene converted ES cells with
      puromycin and neomycin.
AB  - The antibiotic puromycin is an effective inhibitor of protein synthesis and
      puromycin N-acetyl transferase gene could be used as a dominant selection marker.
      We report the effective production of mutant mice from double gene-converted ES
      cells by selection with G418 and puromycin. We confirmed that (i) puromycin
      efficiently inhibited the growth of ES cells at a low-dose (0.1 microgram/ml) and
      for a short time (2 days), independent of G418 selection; (ii) when these
      selected ES cells were injected into eight-cell stage embryos, the cells produced
      chimeras with high levels of chimerism; (iii) these chimeric males were fertile
      and exclusively yielded ES cell-derived offspring; and (iv) each offspring
      contained both neomycin transferase and puromycin N-acetyl transferase genes.

PMID- 7639727
TI  - Cytoplasmic cellular structures control permeability of outer mitochondrial
      membrane for ADP and oxidative phosphorylation in rat liver cells.
AB  - The kinetics of regulation mitochondrial respiration by external ADP in
      permeabilized hepatocytes was studied further. In digitonin-permeabilized
      hepatocytes, the apparent Km for ADP in regulation of respiration was decreased
      from 275 +/- 35 microM in control to 48 +/- 8 microM by a treatment with trypsin
      (15 min, 0.125 mg/ml). In liver tissue homogenates, trypsin treatment similarly
      decreased the Km value for ADP. These results show that ADP diffusion in
      hepatocytes may be retarded due to some unknown cytoplasmic trypsin-sensitive
      protein factor(s) which may be lost during isolation of mitochondria. Since we
      have previously reported a limited permeability of the outer mitochondrial
      membrane in isolated hepatocytes (Saks et al. 1995, Biochem. Biophys. Res.
      Commun., 208, 919-926), we conclude that an important site of control of
      respiration in liver cells in vivo is located at the porin channels of the outer
      mitochondrial membrane.

PMID- 7639728
TI  - Loop-size spacings between CGCG clusters in long segments of human DNA.
AB  - The CGCG tetranucleotides are clustered inside the CpG islands in the genomes of
      vertebrates. In order to study the distribution of the islands in the human
      chromosome we have mapped the loci sensitive to the CGCG specific restriction
      nuclease, in a 1.5 Mb long DNA segment cloned as Yeast Artificial Chromosome
      (YAC). The sites most sensitive to Bsh 1236 I nuclease show chromosomal loop-size
      spacing. This result, as well as the result of nucleotide sequence analysis of
      long genomic segments, suggests that the CGCG are organised in clusters (not
      always undermethylated) which are coincident with GC peaks on the sine wave-like
      curve representing DNA composition along the mammalian chromosome.

PMID- 7639729
TI  - NGF promotes amyloid precursor protein secretion via muscarinic receptor
      activation.
AB  - Processing of beta-amyloid precursor protein (APP) is coupled to several
      neurotransmitter receptors, including m1 muscarinic (m1AChR), and is associated
      with decreased amyloid deposition. Muscarinic agonist-stimulated APP secretion
      and membrane APP were measured in control and in NGF-differentiated PC12 cells
      stably transfected with m1AChR. This secretion was markedly enhanced following
      treatment with 50 ng/ml NGF for 3 days, and was observed using either carbachol
      or the M1-selective agonist AF102B. The effects of NGF were reflected by larger
      reductions in membrane-associated APP levels following muscarinic stimulation.
      These observations imply that M1 muscarinic receptors may act in concert with NGF
      to boost APP processing, and M1-selective agonists may thus be beneficial for
      reducing amyloid deposition by NGF-responsive neurons.

PMID- 7639730
TI  - Molecular cloning of the human gene encoding lanosterol synthase from a liver
      cDNA library.
AB  - Lanosterol synthase [(S)-2,3-epoxysqualene mutase (cyclizing, lanosterol
      forming), EC 5.4.99.7] catalyzes the cyclization of (S)-2,3-oxidosqualene to
      lanosterol in the reaction that forms the sterol nucleus. We report herein the
      cloning and characterization of the human gene (OSC) encoding lanosterol
      synthase, a predicted 83 kDa protein of 732 amino acids. The deduced amino acid
      sequence is 36-40% identical to known yeast and plant homologues and 83%
      identical to Rattus norvegicus lanosterol synthase. The new gene was shown to
      encode lanosterol synthase. The yeast lanosterol synthase deficient mutant SMY8
      was complemented by the human gene, and a cell-free homogenate of SMY8 expressing
      the human gene was shown to convert 2,3-oxidosqualene to lanosterol.

PMID- 7639731
TI  - Poly(ADP-ribose) polymerase activity in various U937 cell subclones with
      different susceptibility to HIV-1 infection: its dramatic decrease following
      persistent virus infection.
AB  - Poly(ADP-ribose) polymerase, a nuclear enzyme, is suggested to be involved in
      apoptotic cell death. It is also known that apoptotic cell death following HIV-1
      infection is the most important feature of AIDS pathogenesis. Thus, to evaluate
      the relations between the enzyme and HIV-1 infection, we examined the enzyme
      activity of several subclones of human promonocytic cell line U937, which showed
      different susceptibility to HIV-1 infection. The nuclear extracts of two "high
      type clones" (possessing high susceptibility to HIV-1 infection) contained
      approximately 4 to 7-fold less enzyme than two low type clones when assayed under
      a full activation of enzyme. Parent clone, possessing an intermediate
      susceptibility to HIV-1, showed an intermediate enzyme level, suggesting that low
      level of this enzyme in cells is important for an effective infection of HIV-1.
      Furthermore, when these U937 subclones persistently infected with HIV-1 were
      examined, a dramatic decrease of the enzyme activity, reaching 2 to 16% of
      uninfected cells, was observed in all of these clones. The levels of poly(ADP
      ribose) glycohydrolase in these clones were relativity unchanged. Activity gel
      analysis and immunoblotting of the enzyme in the clones revealed that the low
      enzyme activities observed in uninfected "high type clones" and all HIV-1
      infected clones were due to a marked decrease of the enzyme protein itself. All
      of these results suggest that HIV-1 infection involves some mechanism to
      downregulate cellular poly(ADP-ribose) polymerase and that a lower level of the
      enzyme may be essential for an effective production of the virus and/or for a
      stable virus/host interaction.

PMID- 7639732
TI  - Fasciola hepatica: rapid identification of newly excysted juvenile proteins.
AB  - The sensitivity of N-terminal sequencing has been used to identify proteins
      expressed by the newly excysted juvenile stage of the parasite Fasciola hepatica.
      Of the seven proteins identified, a number have significant sequence homology to
      the cysteine proteases: cathepsin B, cathepsin L and asparaginyl endoproteinase.
      Proteolytic activity was demonstrated using gelatin substrate sodium dodecyl
      sulphate polyacrylamide gel electrophoresis. In addition, a number of novel
      proteins were identified which shared no significant sequence homology to
      proteins in the databases. The availability of such N-terminal sequence
      information allows rapid identification of major proteins from scarce
      developmental stages and provides the basis for further molecular studies.

PMID- 7639733
TI  - Kinetic studies on cyclophellitol analogues--mechanism-based inactivators.
AB  - The (1R,6S)- and (1R,2S,6S)-diastereoisomers of cyclophellitol were found to be
      effective irreversible inactivators of alpha-D-glucosidase and alpha-D
      mannosidase, respectively. The (1R,6S)-diastereoisomer inactivates brewers yeast
      alpha-D-glucosidase according to pseudo-first order kinetics with inactivation
      constants of Ki = 26.9 microM, ki = 0.401 min-1 while the (1R,2S,6S)
      diastereoisomer inactivates jack beans alpha-D-mannosidase in a similar manner
      with Ki = 120 microM, ki = 2.85 min-1. The irreversibility of these compounds was
      evidenced by the lack of reactivation upon dialysis of the inactivated enzyme.

PMID- 7639734
TI  - Isolation of candidate genes for macular degeneration using an improved solid
      phase subtractive cloning technique.
AB  - An improved solid-phase subtraction procedure was developed to generate a readily
      amplifiable library of short cDNA fragments highly enriched in the macula
      (target) versus the peripheral region (driver) of the monkey neural retina. The
      generated clones were sequenced and 63 were analyzed by northern blotting using
      total RNA from the monkey macula and peripheral retina. The results indicate that
      32% are highly enriched in macula, 36% are below the limits of detection and 32%
      are not enriched. No clones were found which were enriched in the peripheral
      retina. Our technique is therefore successful in identifying novel cDNAs enriched
      in the macula area of the neural retina that may represent potential candidate
      genes for hereditary ocular diseases. It should thus be useful in other
      situations where subtle differences in expression between cell types or tissue
      areas need to be analyzed.

PMID- 7639735
TI  - Segregation of mitochondrial DNAs carrying a pathogenic point mutation
      (tRNA(leu3243)) in cybrid cells.
AB  - To investigate the mechanism of segregation of mitochondrial DNAs (mtDNAs)
      carrying a pathogenic point mutation in the tRNA(leu(UUR)) gene (A to G at
      position 3243) cytoplasts, derived from a heteroplasmic myoblast clone, were
      fused to rhoo cells to create cybrid cells carrying different proportions of
      mutant and wild-type mtDNAs. Although the individual myoblasts used as fusion
      partners contained predominantly mutant mtDNAs (mean proportion 0.77, range 0.46
      0.94), the majority (56%) of the cybrid clones isolated after growth in selective
      medium were homoplasmic wild-type, indicating preferential replication of wild
      type mtDNAs. Long-term culture of heteroplasmic cybrid clones in non-selective
      medium produced no change in the mean proportion of wild-type mtDNAs but an
      increase in population variance, consistent with a purely stochastic segregation
      mechanism. These results are at variance with a previous report suggesting a
      replicative advantage for mtDNAs carrying the tRNA(leu3243) point mutation.

PMID- 7639736
TI  - Endothelial damage induced by nitric oxide: synergism with reactive oxygen
      species.
AB  - Interactions of reactive oxygen and nitrogen species to mediate endothelial cell
      damage were studied in vitro. S-Nitroso-N-acetyl-DL-penicillamine (SNAP), 3
      morpholinosydnonimine-N-ethylcarbamide (SIN-1) and sodiumnitroprusside (SNP) were
      used as NO.-donating agents. The toxicity of SIN-1 (5 mM), which produces both O2
      . and NO., was reduced when catalase was added to remove H2O2 whereas superoxide
      dismutase had a marginal protective influence. Low doses of H2O2 producing
      enzymes added to low doses of SNAP (1 mM) or SNP (5 mM) substantially increased
      toxicity. Such damage was absent when catalase was present, but was still seen in
      the presence of superoxide dismutase. Non toxic doses of KCN (1 mM), antimycin A
      (1 microM), and rotenone (0.5 microM) in order to increase endogeneously produced
      reactive oxygen species increased toxic effects by 20-30% (p < 0.05). In our
      experiments we provide evidence that extracellularly produced H2O2 rather than O2
      . enhances toxicity of NO. against endothelial cells. Likewise, endogeneous
      production of reactive oxygen species may increase toxicity of NO..

PMID- 7639737
TI  - Human nuclear and mitochondrial Mt element-binding proteins to regulatory regions
      of the nuclear respiratory genes and to the mitochondrial promoter region.
AB  - We have found that Mt element-binding proteins (MtEBPs) with the same binding
      capability are present in the nuclei and mitochondria of human, bovine, and rat
      cells. MtEBPs purified from the human nuclei and mitochondria with Mt element
      specific DNA affinity chromatography contained 4 different polypeptides,
      respectively. A UV-induced DNA cross-linking study showed that 47- or 55-kDa of
      the nuclear MtEBP recognizes Mt in the 5'-flanking region of the human cytochrome
      c1 gene and that both 140- and 180-kDa polypeptides of the mitochondrial (mt)
      MtEBPs bind Mts in the human mt promoter region. Mt MtEBPs recognized a Mt4
      element-like sequence within the mt transcription factor A binding site for the
      heavy-strand promoter. These results suggest a MtEBP-mediated coordination
      mechanism between nuclear and mt genetic systems.

PMID- 7639738
TI  - Genomic organization of a mouse type I activin receptor.
AB  - We have characterized the genomic organization of a mouse type I activin
      receptor. Using the mouse tsk7L cDNA, 4 overlapping lambda clones containing the
      activin receptor IA (ActRIA) gene were isolated from a mouse 129 Sv genomic
      library. The mouse ActRIA gene is encoded by 10 exons and spans approximately 40
      kb. The size of the introns was determined and the intron/exon boundaries were
      sequenced. Primer extension analysis of the 5' non-translated region using RNA
      from different organs or tissues revealed a strong transcription start site 68
      nucleotides upstream of the ATG. Knowledge of the structure of the ActRIA gene is
      essential for the production of ActRIA deficient mice by homologous
      recombination.

PMID- 7639739
TI  - Cloning, sequencing and expression of an isoform of cardiac C-protein from the
      Mexican axolotl (Ambystoma mexicanum).
AB  - C-protein, a myosin binding protein, is thought to regulate and stabilize thick
      filaments during assembly of sarcomeric A-bands. Multiple isoforms of C-protein
      have been characterized in avian and mammalian systems. We now report the
      isolation and the nucleic acid sequence of a partial C-protein cDNA clone from an
      axolotl heart cDNA expression library in lambda gt11. The clone was isolated by
      screening the library with a heterologous monoclonal anti-C-protein antibody
      (MF1). Sequence comparison revealed that CPROAxocard1 has an average sequence
      identity of 62-68% at the nuclei acid and 72-78% at the amino acid levels
      respectively to human and chicken sequences. We could not detect any significant
      differences at the levels of expression of the cardiac isoform of C-protein
      (CPROAxocard1) in normal and non-beating heart tissues of the double-recessive
      cardiac lethal mutant (c/c) axolotl, Ambystoma mexicanum. This is the first
      report of a C-protein sequence from an amphibian species.

PMID- 7639741
TI  - Purification and characterization of human pancreatic polypeptide expressed in E.
      coli.
AB  - The region of cDNA encoding human pancreatic polypeptide (hPP) was obtained by
      polymerase chain reaction (PCR) and subcloned into an expression vector. The
      pancreatic polypeptide gene was expressed in Escherichia coli in two versions: as
      a cleavable fusion protein with IgG-binding synthetic ZZ domains of protein A
      from Staphylococcus aureus or with the 1-48 fragment of lambda Cro repressor.
      Site-specific hydrolysis by hydroxylamine was used to cleave the fusion protein,
      releasing the human polypeptide. The structure of the obtained hPP has been
      studied by scanning microcalorimetry and circular dichroism spectrometry. It has
      been shown that hPP in solutions close to neutral has a compact and unique
      spatial structure with an extended hydrophobic core. This structure is stable at
      20 degrees C and co-operatively breaks down upon heating from this temperature.

PMID- 7639740
TI  - Transcriptional properties of oligonucleosomal templates containing acetylated
      (H3-H4)2 tetramers.
AB  - Direct chemical acetylation of an oligonucleosomal template for bacteriophage T7
      RNA polymerase is accompanied by a substantial increase in its capability to
      support RNA synthesis. The template was assembled from a plasmid, containing a
      promoter and a terminator for T7 RNA polymerase, plus one (H3-H4)2 tetramer and
      two H2A.H2B dimers for each 200 base pairs of DNA. Under the employed conditions,
      acetylation modifies in a preferential way the lysine residues located in the
      amino-terminal domains of core histones. When the template is assembled with
      acetylated tetramers and untreated dimers, its efficiency in promoting RNA
      synthesis is also largely increased. Since a previous work reported
      transcriptional stimulation upon acetylation of H2A.H2B dimers [Puerta et al.
      (1995) Biochem. Biophys. Res. Commun. 210, 409], the transcriptional repression
      brought about by core histone octamers seems to require that the amino-terminal
      domains of both (H3.H4)2 tetramers and H2A.H2B dimers are not acetylated.

PMID- 7639742
TI  - Ubiquitination of the rat uterine estrogen receptor: dependence on estradiol.
AB  - Using polyclonal antibodies against estrogen receptor and ubiquitin, the
      ubiquitination of the estrogen receptor has been demonstrated in both in vitro
      and in vivo conditions. The ubiquitination of the estrogen receptor is estradiol
      specific and is enhanced by estradiol. Estrogen withdrawal is associated with
      decreased ubiquitination of the estrogen receptor.

PMID- 7639743
TI  - Cloning of no tI-cleaved genomic DNA fragments appearing as spots in 2D gel
      electrophoresis.
AB  - RLGS (Restriction Landmark Genomic Scanning) is a simple and rapid scanning of
      genomic DNA in two-dimensional electrophoresis. Human genomic DNA is first
      cleaved by NotI, and the cleaved ends are radio-labeled and cleaved further by
      EcoRV, followed by size-fractionation by first dimensional electrophoresis. The
      sample is then cleaved in situ by the second enzyme HinfI and resolved by the
      second dimensional electrophoresis. Nearly 2,000 spots emerge with spot
      intensities reflecting the copy number in the genome. Because of the resolving
      power and capacity to scan the entire genome, RLGS has been used to monitor
      genomic aberrations and imprinting. Here, we report a means of cloning the DNA in
      spots. The DNA was eluted and ligated to biotinylated NotI and HinfI likers
      followed by affinity separation using streptavidin. The ligated fragment was
      recovered by EcoRV cleavage, the target sequence of which was located in the NotI
      linker and amplified by PCR using a primer pair, the sequences of which lie in
      the linkers. The products were then cloned into a vector for further tests. An
      amplified spot in stomach cancer genomic DNA and a dwindling spot in liver cancer
      genomic DNA were taken as examples for cloning.

PMID- 7639744
TI  - Overexpression of mammalian protein kinase C-zeta does not affect the growth
      characteristics of NIH 3T3 cells.
AB  - The structure of protein kinase C zeta (PKC zeta) is unusual with respect to
      other PKCs, as it lacks the C2 domain and possesses only one zinc finger region.
      Consequently, PKC zeta can not be activated by diacylglycerol or phorbol esters
      and is not downregulated by prolonged treatment by phorbol esters nor blocked by
      commonly utilized PKC inhibitors. In this study, we have explored the idea that
      PKC zeta might participate in proliferative pathways. Our findings show that
      marked overexpression of mammalian PKC zeta does not alter the growth
      characteristics of NIH 3T3 cells, nor induces cellular transformation.
      Furthermore, mammalian PKC zeta does not potentiate the transforming ability of
      oncogenes such as ras, sis and the muscarinic receptor m1. In this context, PKC
      zeta or its dominant negative mutant do not affect MAP kinase activation by
      oncogenes or growth factors. Taken together, our findings demonstrate that
      mammalian PKC zeta does not directly participate in signaling pathways involved
      in oncogenic transformation.

PMID- 7639745
TI  - Molecular characterization of the murine syk protein tyrosine kinase cDNA,
      transcripts and protein.
AB  - Using a RT-PCR based cloning strategy and conventional cDNA library screening we
      have cloned the murine syk cDNA. Sequence analysis of the 5350bp full length cDNA
      revealed a 5' untranslated region (UTR) of 477bp, an open reading frame of 1884bp
      and an unusually long 3' UTR of 2989bp containing a polyadenylation signal. The
      cDNA encodes a putative protein of 628 amino acids with two SH2 domains located N
      terminally of the protein tyrosine kinase domain. The highest overall homology,
      98%, was observed to the rat syk. Northern blot analysis revealed that the murine
      syk protein is encoded by two transcripts of approximately 5.4 and 3.5kb, the
      difference in size being attributable to differences in the 3' UTR. Rabbit
      antisera raised against a pGEX-syk bacterial fusion protein recognized
      specifically a protein of approximately 67kd with intrinsic protein tyrosine
      kinase activity in lymphoid cell extracts. The size of the syk protein could be
      confirmed by in vitro transcription/translation of the full length clone.
      Expression of syk was found in a variety of mouse organs with the highest levels
      in spleen, heart, mammary gland and thymus and in several lymphoid cell lines.
      The majority of the expression observed in whole mammary glands originated from
      the lymph node. Upregulated expression of syk was observed in aggressive,
      metastasizing mammary gland tumours but not in well differentiated, non
      metastasizing tumors.

PMID- 7639746
TI  - Topoisomerase-II-mediated DNA cleavage within the human ribosomal genes.
AB  - The interaction of topoisomerase II (topo II) with human ribosomal DNA (rDNA) was
      investigated in vivo using the antitumoral drug VM26, a specific inhibitor of
      topo II, that stabilizes the transient cleavable complex. rDNA-protein complexes
      isolated from nucleoli of TG cells were analyzed for double strand breaks with
      probes that covered almost all intergenic transcribed spacer (IGS) and all
      transcribed sequences of tandem repeat ribosomal DNA genes. Preferential cleavage
      sites were present in only a part of nucleolar rDNA, i.e., the transcribed
      region. Proteins, purified from the same complexes, were analyzed by Western-blot
      and stained by an antiserum against both topo II forms, showing the presence of
      topo II beta.

PMID- 7639747
TI  - Vanadium-diascorbates are strong candidates for endogenous ouabain-like factors
      in human urine: effects on Na-K-ATPase enzyme kinetics.
AB  - Recently, we isolated from the urine of salt-loaded healthy subjects a more polar
      ouabain-like factor OLF-1 and a more apolar OLF-2, the latter cross-reacted with
      a digoxin anti-body. They were purified to single compounds with dose-dependent
      Na-K-ATPase inhibition. Mass-spectroscopy (MS) showed a Mr of around 400 and 1H
      NMR- and IR-spectroscopy suggested diascorbic acid salts, i.e., vanadium (V)
      diascorbates (Mr 403) with similar elution times from RP-HPLC as OLFs. IC50 was 9
      x 10(-5)M for VIV-diascorbate as compared to 2 x 10(-6)M for Vv-diascorbate.
      Enzyme inhibition was non-competitive with respect to sodium and Mg-ATP; p-NPPase
      assay showed strong inhibition in its E2-configuration. We suggest that V
      diascorbates represent endogenous OLFs excreted in human urine.

PMID- 7639748
TI  - Dystrophin, the protein that promotes membrane resistance.
AB  - Deficiency of dystrophin, a 427-kDa subsarcolemma membrane protein, is
      responsible for Duchenne muscular dystrophy. The function of this protein is not
      clear but its subcellular distribution suggests that it is an important link
      between the cytoskeleton and the extracellular matrix, thus maintaining membrane
      integrity. The N-terminus of dystrophin was shown to bind actin in vivo and in
      vitro via two major actin binding sites. The role of dystrophin/actin
      interactions has been investigated and the results presented here demonstrate for
      the first time that the N-terminal part of dystrophin is able (i) to interact
      with G-actin monomers, and (ii) to slowly promote G->F actin transformation. This
      conversion was shown to be stimulated the presence of calmodulin in a calcium
      dependent manner. This is evidence that dystrophin is an anchor protein for actin
      involved in the control of membrane cell shape deformation and developing a
      calmodulin-calcium induced F-actin network, thus stiffening the myotube membrane
      cytoskeleton.

PMID- 7639749
TI  - A relatively small 5' regulatory region of esterase S gene of Drosophila virilis
      determines the specific expression as revealed in transgenic experiments.
AB  - Expression of the esterase S gene of Drosophila virilis was studied in transgenic
      experiments. Truncated genomic copy of this gene including 400 bp of 5'
      regulatory region was integrated into the genome of Drosophila melanogaster. The
      products of the transferred gene were detected. It was found that strict temporal
      and tissue specificity of the esterase S gene expression is conserved in
      transformed flies. The results suggest that this specificity is evidently
      determined by the regulatory region of the esterase S gene and controlled by cis
      mechanism.

PMID- 7639750
TI  - N-acetylglucosaminidase inhibitor isolated from the vitelline coat of ascidian
      eggs is a candidate sperm receptor.
AB  - An inhibitor against the egg beta-D-N-acetylglucosaminidase (GlcNAcase) was
      purified from the vitelline coat of eggs of the ascidian, Halocynthia roretzi.
      The purified inhibitor gave a single band with an apparent molecular mass of 70
      kDa on SDS-PAGE under non-reducing conditions. The GlcNAcase inhibitor potently
      inhibited the ascidian egg GlcNAcase activity, and also substantially inhibited
      the GlcNAcase activity in the ascidian sperm extract, although to lesser extent.
      In contrast, it showed little inhibitory effect on the activity of GlcNAcase from
      Jack beans. This inhibitor was found to block the binding of sperm to the
      vitelline coat of the eggs in a concentration-dependent manner. These results
      strongly suggest that the GlcNAcase inhibitor isolated from the vitelline coat
      functions in the binding of sperm to the egg coat, as a possible sperm receptor.

PMID- 7639751
TI  - Arrest of cell growth by necdin, a nuclear protein expressed in postmitotic
      neurons.
AB  - Necdin is a 325 amino acid residue protein localized to the nuclei of postmitotic
      neurons, which withdraw permanently from the cell cycle. To examine whether
      necdin confers the postmitotic phenotype, necdin cDNA was stably transfected into
      NIH3T3 cells, in which the protein was conditionally expressed using a eukaryotic
      lac repressor-operator expression system. When the transfectants were induced to
      express ectopic necdin, cell growth was arrested without appreciable reduction in
      cell viability. The expressed necdin molecule was localized to the nuclei of the
      transfectants. These results suggest that necdin is a nuclear factor that governs
      the permanent arrest of cell growth of postmitotic neurons during development of
      the nervous systems of vertebrates.

PMID- 7639752
TI  - Ligand-induced polyubiquitination of receptor tyrosine kinases.
AB  - The platelet-derived growth factor beta-receptor undergoes polyubiquitination as
      a consequence of ligand binding. In the present study, we have examined the
      ligand-induced receptor ubiquitination also in the other receptor tyrosine kinase
      (structurally different) subfamilies by immunoblotting with anti-ubiquitin
      antiserum. In addition to the platelet-derived growth factor alpha- and beta
      receptors, all the monomeric receptor tyrosine kinases examined, such as the
      receptors for epidermal growth factor (subfamily I), colony stimulating factor-1
      (subfamily III), and fibroblast growth factor (subfamily IV), were found to be
      ubiquitinated after ligand stimulation. However, the insulin receptor (subfamily
      II), which is a tetrameric molecule, was not. These data suggest that the ligand
      induced polyubiquitination of the receptor is a general phenomenon observed in
      most of the monomeric receptor tyrosine kinases.

PMID- 7639753
TI  - A mammalian delayed-early response gene encodes HNP36, a novel, conserved
      nucleolar protein.
AB  - Murine fibroblasts respond to mitogens by sequential gene expression in which
      immediate-early, or primary response, gene transcription factors direct
      expression of secondary transcripts encoded by delayed-early response (DER)
      genes. DER gene products include growth progression factors, but the products of
      several novel cDNAs are unknown. Murine and human cDNAs derived from one novel
      DER gene (DER12) were characterized to identify its product and to probe its role
      in the growth response. Both sequences encoded a hydrophobic 36 kD protein
      (HNP36) that was related to the yeast protein, FUN26. Anti-murine HNP36
      antibodies were prepared and shown to immunoprecipitate both mammalian in vitro
      translation products. Immunocytochemical staining indicated localization of HNP36
      to the nucleolus where its concentration increased after mitogen stimulation.
      Although HNP36 protein function is unknown, its identification as a nucleolar
      gene transcriptionally activated by growth factors implicates it as participating
      in the proliferative response.

PMID- 7639754
TI  - Type I, II and III inositol 1,4,5-trisphosphate receptor co-immunoprecipitation
      as evidence for the existence of heterotetrameric receptor complexes.
AB  - The recently described co-expression of type I, II and III inositol 1,4,5
      trisphosphate (InsP3) receptors in the same cell type has raised the issue of
      whether these proteins exist as homotetramers or heterotetramers. To address this
      question, InsP3 receptors were immunoprecipitated with specific antibodies and
      then probed for co-immunoprecipitating proteins. This revealed that type I, II
      and III InsP3 receptors co-immunoprecipitate and thus, exist in heteromeric
      complexes. This situation was maintained when the relative abundance of InsP3
      receptors was altered radically during cell differentiation. Thus,
      heterotetrameric InsP3 receptors are likely to contribute towards signaling in
      cells expressing more than one receptor type.

PMID- 7639755
TI  - Survival motor neuron gene transcript analysis in muscles from spinal muscular
      atrophy patients.
AB  - We have identified and characterized four different mRNA isoforms of the survival
      motor neuron (SMN) gene from skeletal muscle of 9 SMA patients and 15 unaffected
      controls. These isoforms appear to be generated by combinatorial splicing of both
      exons 5 and 7 of the SMN telomeric and centromeric gene copies. The full-size and
      the truncated SMN-1b isoforms of the telomeric SMN copy are significantly reduced
      in muscle of SMA patients, irrespective of the disease types. Our results suggest
      that multiple RNA splicing is operative in the two SMN-related genes and that SMN
      related polypeptides may be active in the muscle.

PMID- 7639756
TI  - Influence of caltropin on the caldesmon induced polymerization of G-actin.
AB  - The effect of caltropin (CaT) on the caldesmon (CaD)-G-actin interaction was
      monitored by viscosity measurements, bioassays measuring the release of inorganic
      phosphate (Pi) following G-actin polymerization and fluorescence studies using
      acrylodan labelled G-actin. CaD induced polymerization of G-actin into filaments
      in the absence of salt was accompanied by an increase in relative viscosity. This
      effect of CaD was essentially abolished by CaT in the presence of Ca2+. In
      bioassays the rate of Pi release was reduced significantly in the presence of
      Ca2+/CaT. Acrylodan labelled G-actin when excited at 375 nm exhibited an emission
      maximum at 478 nm. Polymerization of G-actin resulted in shifting the emission
      maximum to 465 nm. When CaD was added to G-actin containing Ca2+/CaT, the rate of
      G-actin polymerization was reduced considerably, suggesting that CaT interferes
      in the CaD-G-actin interaction.

PMID- 7639757
TI  - Structural investigation and kinetic characterization of potential cleavage sites
      of HIV GP160 by human furin and PC1.
AB  - A key event in the biosynthesis of the human immunodeficiency virus is the
      maturation of the gp160 precursor generating gp120 and gp41, two proteins that
      are fundamental for the infective process. In vivo, gp160 is specifically cleaved
      at the 515-519 site (REKR decreases A), in spite of the presence in its sequence
      of another consensus sequence KAKR decreases R (residues 507-511). Comparative
      kinetic studies on synthetic peptides reproducing different sequences of gp160 by
      the enzymes PC1 and furin are reported in this paper. The data demonstrate the
      higher efficiency of furin in the cleavage of peptidic substrates with respect to
      PC1 and its preference for REKR decreases A vs. KAKR decreases R. Furthermore,
      furin and PC1 are unable to process peptides patterned on the sequence 307-330 of
      specific viral strains of the gp120 V3 loop.

PMID- 7639758
TI  - Identification of a de Novo point mutation resulting in infantile form of Pompe's
      disease.

PMID- 7639759
TI  - Similarities of an autoantigen in aneurysmal disease of the human abdominal aorta
      to a 36-kDa microfibril-associated bovine aortic glycoprotein.
AB  - Immunoglobulin G (IgG) from human aneurysmal aorta was used to partially purify
      an aortic protein with an apparent MW approximately 80 kDa. Amino acid sequencing
      of a tryptic digest revealed two sequences with homology to mouse tenascin-X. The
      autoimmune IgG was then shown to react with purified human tenascin, and a rabbit
      polyclonal anti-human tenascin antibody was found to react with the purified
      autoantigen. These observations suggest that the autoantigen of abdominal aortic
      aneurysm disease may be homologous to a calcium-binding member of the tenascin
      superfamily that has been identified by others in pig and cow.

PMID- 7639761
TI  - Expression, purification, and neurotrophic activity of amyloid precursor protein
      secreted forms produced by yeast.
AB  - The secreted form of amyloid precursor protein (APPs) including most of the
      extracellular domain of APP is released from the cell surface, suggesting
      physiological significance of APPs in vivo. We used the methylotrophic yeast
      Pichia pastoris as a host system for the production of recombinant APPs (rAPPs).
      Two rAPPss derived from isoforms of APP (APP695 and APP770) were secreted into
      the culture medium from the yeast, which carried cDNA encoding the N-terminal
      portion of APP under the control of a P. pastoris alcohol oxidase promoter. Like
      APPss produced by the transfected COS-1 cells, the purified rAPPss from yeast
      were shown to be biologically active in terms of neurite outgrowth of embryonic
      rat neocortical explants. These rAPPss could be valuable tools for investigating
      the biological functions of APPss.

PMID- 7639762
TI  - 1,25-Dihydroxyvitamin D3 regulation of myocardial growth and c-myc levels in the
      rat heart.
AB  - In this report we demonstrate that rats maintained on a calcium supplemented
      vitamin D3-deficient diet for nine weeks showed an increase in heart to body
      weight ratio. Morphometric analysis indicated that vitamin D3 deficiency produced
      cardiac myocytes that were smaller yet more numerous, indicating hyperplasia.
      Western blot analysis showed that vitamin D3 deficiency also resulted in
      increased c-myc protein levels in the hearts of vitamin D3-deficient rats.
      Furthermore, 1,25-dihydroxyvitamin D3 reduced c-myc protein levels in primary
      cultures of ventricular myocytes from neonatal rat hearts. Our data suggest a
      possible relationship between myocyte hyperplasia and increased c-myc levels in
      the vitamin D3-deficient rat heart.

PMID- 7639760
TI  - High- and low-affinity CCKA receptor states mediate specific growth inhibitory
      effects on CHO cells.
AB  - To relate specific effects on growth and transformation to activation of specific
      affinity states of the CCKA receptor stably expressed in CHO cells we compared
      responses to the CCK analogues JMV-180 and CCK8. CCK8 led to an inhibition of
      both cell proliferation and transformation. Effects on proliferation were
      indicated by a reduction of DNA synthesis and cell numbers. Effects on
      transformation were indicated by a reduction of colony formation in soft-agar.
      JMV-180 did not inhibit cell proliferation although a small inhibitory effect on
      DNA synthesis was observed. JMV-180 inhibited the maximal effects of CCK8 on cell
      proliferation and DNA synthesis. In contrast, JMV-180 substantially inhibited
      cell colony formation in soft-agar and did not inhibit the effects of CCK8 on
      this parameter. Collectively these data with receptor affinity state specific
      analogues indicated that inhibition of cell proliferation and growth in soft-agar
      can be attributed to activation of distinct affinity states. Thus, different
      second messengers are likely responsible for the inhibitory effects on anchorage
      dependent and -independent growth.

PMID- 7639763
TI  - Cloning and functional expression of a metalloendopeptidase from human brain with
      the ability to cleave a beta-APP substrate peptide.
AB  - Using a combination of PCR and hybridization screening, we have isolated a cDNA
      clone for a metalloendopeptidase (h-MP78) from a human temporal cortex library.
      This 2.5-kb cDNA encodes a 689-amino acid protein with a predicted molecular mass
      of approximately 78.5 kDa. The primary structure of h-MP78 exhibits high
      similarity to those of porcine (94%) and rat (92%) thimet oligopeptidase.
      Expression of the cDNA in HEK-293 resulted in the production of an active enzyme
      able to cleave a chromogenic beta-APP derived substrate peptide KTEEISEVKM-P
      nitro-anilide. RNA blot analysis of various human tissues revealed one major
      species of h-MP78 mRNA of approximately 2.55 kb. The highest level of mRNA was
      found in the brain.

PMID- 7639764
TI  - Phosphorylation of proteasome substrate by a protein kinase associated with the
      26 S proteasome is linked to the ATP-dependent proteolysis of the 26 S
      proteasome.
AB  - A protein kinase phosphorylating the 45-kDa proteasome subunit was co-purified
      with the 26 S proteasome from the porcine heart. This kinase appears to be
      associated with the 26 S proteasome, since the kinase activity was co-eluted with
      the 26 S proteasome on Superose 6 FPLC and immunoprecipitated with anti-20 S
      proteasome antibody. This kinase also phosphorylated the casein. Furthermore, the
      phosphorylated casein was more efficiently hydrolyzed by the 26 S proteasome than
      the dephosphorylated casein without ATP. Inhibition patterns of kinase inhibitors
      against the 45 kDa subunit and casein were well in accord with the inhibition
      pattern against the ATP-dependent proteolysis of the 26 S proteasome, suggesting
      that the phosphorylation of casein by a protein kinase associated with the 26 S
      proteasome is linked to the ATP-dependent proteolysis of the 26 S proteasome.

PMID- 7639765
TI  - Mutational specificity of the ferrous ion in a supF gene of Escherichia coli.
AB  - A plasmid, pZ189, was treated with Fe2+/EDTA, and mutagenesis was determined by
      DNA sequencing. In the fgp+ Escherichia coli host, 78% were base substitutions,
      with G:C- > C:G transversion (58.7%) predominant, followed by G:C- > T:A
      transversion (28.3%). In the fpg-1 mutant, 88% were base substitutions among
      which 46% were G:C- > C:G and 42% G:C- > T:A. Fe2+ resulted in increased
      formation of 8-hydroxydeoxyguanosine (8-ohdG) in pZ189 DNA. The origin of Fe(2+)
      induced G:C- > T:A transversion may be 8-ohdG; on the other hand, the origin of
      G:C- > C:G is neither 8-ohdG nor 2,6-diamino-4-hydroxy-5-formamidopyrimidine.

PMID- 7639766
TI  - Uptake of exogenous DNA by rat liver: effect of cationic lipids.
AB  - We have investigated by using centrifugation methods, the uptake and the
      intracellular fate of 35S DNA by rat liver and the effect on these processes of N
      (1-(2,3-dioleoxyloxy)propyl)-N,N,N,-trimethylammonium-methyl-sul fate(DOTAP,
      Boehringer, Mannheim, Germany), an artificial cationic lipid frequently used in
      transfection experiments. Labeled DNA molecules are quickly taken up by the liver
      but a progressive degradation takes place with time. Subcellular distribution of
      the radioactivity was established after differential and isopycnic
      centrifugation. Results indicate that 35S DNA enters liver cells by endocytosis
      and reaches lysosomes. The uptake of 35S DNA is not modified if the molecule is
      associated with DOTAP but marked differences are observed after internalization
      of the macromolecule. When DOTAP is used, radioactive products remain for a long
      time in low density organelles distinct from lysosomes indicating that the
      transfer of internalized DNA to these organelles is delayed by the cationic
      lipid. These results suggest that cationic lipids could favor transfection by
      preventing the delivery of DNA to lysosomes, allowing these molecules to be kept
      intact and available for transfer from endosomes to cytosol for a long time.

PMID- 7639767
TI  - Role of porins in the antibiotic susceptibility of Pseudomonas aeruginosa:
      construction of mutants with deletions in the multiple porin genes.
AB  - We inserted deletions in the chromosomal genes of Pseudomonas aeruginosa coded
      for the outer membrane porins, proteins C, D2, or E1, and all possible
      combinations of these proteins by the gene replacement technique and selecting
      for imipenem-resistance. Determination of the minimum inhibitory concentrations
      of beta-lactams, fluoroquinolones, chloramphenicol and gentamicin in these
      mutants revealed that most mutants showed equal susceptibility to the porin
      sufficient strain. The only exception was that imipenem and meropenem showed
      increased minimum inhibitory concentrations in all of the mutants lacking protein
      D2. These results firmly established that the P. aeruginosa porins identified so
      far form the pores do not accommodate the passage of most antipseudomonal
      antibiotics, with the exception of carbapenems.

PMID- 7639768
TI  - Platelets are the primary source of amyloid beta-peptide in human blood.
AB  - The main component of Alzheimer's disease (AD) amyloid deposits is amyloid beta
      peptide (A beta), a fragment of the larger amyloid precursor protein (APP). The
      cellular source of A beta is not known, but a circulatory origin has been
      postulated. We studied human blood from healthy individuals and found that
      platelets account for almost 90% of the total anti-A beta immunoreactivity
      detected in whole blood. Using reverse-phase HPLC, we identified a platelet
      peptide which corresponds to A beta by three criteria: (a) it shares a retention
      time with the synthetic A beta 1-40 peptide in two consecutive HPLC tests; (b) it
      interacts with two anti-A beta antibodies in separate ELISAs; and, (c) its
      partial N-terminal amino acid sequence closely matches that of A beta. The
      detection of this peptide in platelets indicates that, aside from the well-known
      non-amyloidogenic (secretory) pathway, the processing of APP in platelets from
      healthy individuals also involves an amyloidogenic pathway. These findings are
      consistent with the view that platelets are one of the major sources of A beta in
      the circulation.

PMID- 7639769
TI  - Cell wall structural proteins--can we deduce function from sequence?

PMID- 7639770
TI  - Characterization of hepta-beta-glucoside elicitor-binding protein(s) in soybean.
AB  - We are studying the cellular signalling pathway leading to pterocarpan
      phytoalexin biosynthesis in soybean that is induced by a branched hepta-beta
      glucoside originally isolated from the mycelial walls of the phytopathogenic
      oomycete, Phytophthora megasperma f. sp. glycinea. Our research has focused on
      the first step in this signal pathway, namely the specific recognition of the
      hepta-beta-glucoside elicitor by plasma-membrane-localized binding protein(s) in
      soybean cells. Binding of a radio-iodinated derivative of the elicitor-active
      hepta-beta-glucoside by membrane elicitor-binding proteins is specific,
      reversible, saturable and of high affinity (Kd = 0.75 nM). After solubilization
      using the non-ionic detergent n-dodecylsucrose, the elicitor-binding proteins
      retain the binding affinity (Kd = 1.8 nM) for the radiolabelled elicitor and the
      binding specificity for elicitor-active oligoglucosides. A direct correlation is
      observed between the ability of elicitor-active and structurally related inactive
      oligoglucosides to displace labelled elicitor from the elicitor-binding proteins
      and the elicitor activity of the oligosaccharides. Thus, the elicitor-binding
      proteins recognize the same structural elements of the hepta-beta-glucoside
      elicitor that are essential for its phytoalexin-inducing activity, suggesting
      that the elicitor-binding proteins are physiological receptors for the elicitor.
      Current research is directed toward the purification and cloning of the hepta
      beta-glucoside elicitor-binding proteins. Purification and characterization of
      the hepta-beta-glucoside-binding protein(s) or their corresponding cDNAs is a
      first step toward elucidating how the hepta-beta-glucoside elicitor triggers the
      signal transduction pathway that ultimately leads to the synthesis of
      phytoalexins in soybean.

PMID- 7639771
TI  - Cytosolic protons as secondary messengers in elicitor-induced defence responses.
AB  - A variety of early elicitor-induced membrane responses have been described, and
      their possible role in the generation of second messengers involved in the
      cascades of events leading to the activation of defence genes is actively
      investigated. Treatment of tobacco cells with a crude elicitor preparation from
      Phytophthora megasperma, purified oligouronides and a commercial pectate lyase,
      induce a common set of membrane reactions similar to those described in a variety
      of plant material, i.e. efflux of K+, extracellular alkalinization, net Ca2+
      uptake and membrane depolarization. In the same conditions the three elicitors
      stimulate the activity of phenylalanine ammonia-lyase (PAL) and O-diphenol
      methyltransferase (OMT), two enzymes of the phenylpropanoid pathway. A good
      correlation between the intensity of the membrane response and the extent of
      enzyme stimulation has been observed. Cytosolic acidifications have also been
      measured as a rapid response to the different elicitor preparations used. These
      results show that plant cells (which usually succeed in counteracting pH
      perturbing processes associated with their metabolism, with the transport of
      solutes or with the effect of various factors from the environment) display
      significant variation in the concentration of cytosolic protons in specific
      physiological circumstances, such as the perception of signals inducing defence
      reactions. Direct evidence that these cytosolic pH changes could be interpreted
      by plant cells as messages involved in triggering defence responses is provided
      by experiments showing that artificial acidifications of the cytoplasm lead to a
      co-ordinated stimulation of PAL and OMT. These results stress the need to explore
      in more detail the role played by cytoplasmic mechanisms underlying those pH
      changes.

PMID- 7639772
TI  - Signal transduction pathways in plant pathogenesis response.

PMID- 7639773
TI  - Signals involved in the wound-induced expression of the proteinase inhibitor II
      gene of potato.

PMID- 7639774
TI  - Polypeptide signalling for plant defence genes.
AB  - The synthesis of proteinase inhibitor proteins in response to wounding is a
      defensive response against pest and pathogen attacks. Wounding of leaves results
      in the release of a mobile wound signal which induces proteinase inhibitor
      synthesis throughout the plant. The signal transduction pathway regulating this
      response is not fully understood, but several compounds have been identified
      which are capable of inducing proteinase inhibitor synthesis in tomato and potato
      leaves. These compounds include cell wall fragments of both plant and pathogen
      origin [1-3], abscisic acid [4], jasmonic acid [5] and, most recently, an 18
      amino-acid polypeptide, called systemin, isolated from tomato leaves [6]. In this
      chapter, we describe the properties of systemin and its precursor prosystemin,
      and we summarize the evidence supporting a role for systemin as an initial signal
      that regulates proteinase inhibitor synthesis in response to wounding.

PMID- 7639775
TI  - Molecular and structural features of the pistil of Nicotiana alata.

PMID- 7639776
TI  - Signalling events in the wound response of tomato plants.
AB  - The wound response of tomato plants provides a useful experimental system to
      analyse local and systemic signalling events. Wounding one region on the plant
      leads to changes in the expression of genes at the local site of damage and
      elsewhere in unwounded tissues. A wound stimulus is thus converted to signal(s)
      that are transduced locally and signals that are involved in establishing long
      distance spread of the initial stimulus. Data from studies at Leeds will be
      integrated into a wider discussion of the available evidence, to work towards an
      integrated model for understanding signalling events in the wound response.

PMID- 7639777
TI  - Regulation of gene expression in ripening fruits by sense and antisense genes.

PMID- 7639778
TI  - Perception and transduction of an elicitor signal in cultured parsley cells.
AB  - Treatment of cultured parsley cells or protoplasts with a purified extracellular
      glycoprotein from Phytophthora megasperma f.sp. glycinea induces the
      transcription of the same set of defence-related genes as is activated in parsley
      leaves upon infection. Elicitor activity was shown to reside in a specific
      portion of the protein moiety which was isolated, sequenced and synthesized.
      Partial cDNAs encoding the entire mature protein as well as other related
      proteins have been isolated, indicating the presence of a small gene family. The
      elicitor-active oligopeptide is located in the C-terminal portion of the deduced
      amino acid sequence. Binding of the elicitor to target sites on the parsley
      plasma membrane appears to be the initial event in defence gene activation. The
      subsequent intracellular transduction of the elicitor signal was shown to involve
      rapid and transient influxes of Ca2+ and H+, as well as effluxes of K+ and Cl-.
      Inhibition of elicitor-induced ion fluxes by channel blockers also inhibited
      phytoalexin synthesis, while stimulation of similar ion fluxes by treatment of
      cells or protoplasts with the polyene antibiotic, amphotericin B, induced the
      production of phytoalexins and activated the complete set of defence-related
      genes in the absence of elicitor.

PMID- 7639779
TI  - Using T-DNA tagging to search for genes involved in the mechanism of phytohormone
      action.

PMID- 7639780
TI  - Molecular biology of resistance to potato virus X in potato.
AB  - It has been proposed that plants express resistance to pathogens when the product
      of a resistance gene interacts with an elicitor molecule produced by the
      pathogen. Although there is one instance with tobacco mosaic virus (TMV) in which
      virus resistance is known to act through the same type of mechanism, it is not
      known whether this model accounts generally for resistance interactions with
      plant viruses. To address this issue the interactions of resistance genes in
      potato with potato virus X (PVX) have been analysed at the molecular level. PVX
      is an RNA virus that is affected by three different types of resistance locus in
      various potato cultivars. By using recombinant isolates of PVX, incorporating
      components of strains or mutant viruses able to overcome or avoid the effects of
      the resistance loci, we have identified different regions of the viral genome
      that determine the outcome of the resistance interaction. This information has
      allowed us to investigate the resistance in detail. For example, with the
      resistance specified by the Rx locus, it has been shown that the coat protein is
      an avirulence determinant and elicitor of an induced resistance. This resistance
      acts by reducing virus accumulation in the inoculated cell. Although the
      recognition component of the resistance is highly specific, the induced response
      is apparently non-specific and is effective against viruses unrelated to PVX in
      cells doubly inoculated with PVX and a second virus. The recognition function of
      Rx is also expressed in Gomphrena globosa which is a non-host plant of PVX. Based
      on these data, we propose that virus resistance fits the paradigm of resistance
      to fungal and bacterial pathogens and that there are similarities between the
      mechanism of cultivar specific resistance and non-host resistance to pathogen
      attack. Further analysis of the mechanism of the non-specific response phase may
      ultimately allow genetic engineering of broad-spectrum virus resistance in crop
      plants.

PMID- 7639781
TI  - Induction, modification, and perception of the salicylic acid signal in plant
      defence.
AB  - Endogenous salicylic acid (SA) levels increase and several families of
      pathogenesis-related genes (including PR-1 and PR-2) are induced during the
      resistance response of tobacco to tobacco mosaic virus (TMV) infection. We have
      found that at a temperature (32 degrees C) that prevents the induction of PR
      genes and resistance, the increases in SA levels were eliminated. However, when
      the resistance response was restored by shifting inoculated plants to lower
      temperatures, SA levels increased dramatically and preceded PR-1 gene expression
      and necrotic lesion formation associated with resistance. SA was also found in a
      conjugated form whose levels increased in parallel with the free SA levels. This
      SA beta-glucoside (SAG) was as active as SA in inducing PR-1 gene expression. PR
      1 gene induction by SAG was preceded by a transient release of SA. The existence
      of a mechanism that releases SA from SAG suggests a possible role for SAG in the
      maintenance of systemic acquired resistance. Previously, we identified a soluble
      salicylic acid-binding protein (SABP) in tobacco whose properties suggest that it
      may play a role in transmitting the SA signal during plant defence responses.
      This SABP has been purified 250-fold by sequential chromatography on DEAE
      Sephacel, Sephacryl S-300, Blue Dextran-Agarose and Superose 6. Several
      monoclonal antibodies (mAbs) raised against the highly purified SABP
      immunoprecipitated the SA-binding activity and a 280 kDa protein. This 280 kDa
      protein also co-purified with the SA-binding activity during the various
      chromatography steps, suggesting that it was responsible for binding SA.
      Immunoblot analysis with the SABP-specific mAbs also detected the 280 kDa protein
      in highly purified preparations of SABP. However, in crude homogenates these mAbs
      only recognized a 57 kDa protein. These and other results suggest that SABP is a
      multimeric complex which contains, at least, a 57 kDa protein and whose
      components are readily cross-linked during purification.

PMID- 7639783
TI  - Molecular mechanisms underlying induction of plant defence gene transcription.

PMID- 7639782
TI  - Regulation of gene expression in bacterial pathogens.

PMID- 7639784
TI  - Photomorphogenic mutants of tomato.

PMID- 7639785
TI  - Genes controlling Arabidopsis photomorphogenesis.

PMID- 7639786
TI  - Cloning and characterization of cDNAs encoding oat PF1: a protein that binds to
      the PE1 region in the oat phytochrome A3 gene promoter.
AB  - In monocotyledons, the expression of the oat phytochrome A gene (PHYA) is down
      regulated by phytochrome itself. This autoregulatory repression is the most rapid
      light-induced effect on gene expression reported in plants to date. A functional
      analysis of the oat PHYA3 gene minimal promoter in a rice transient expression
      assay has identified two promoter elements, PE1 and PE3, that interact
      synergistically in positive regulation. We have isolated an oat cDNA clone (pO2)
      that encodes a DNA-binding protein that binds to the PE1 region of the oat PHYA3
      gene promoter. The in vitro binding properties of the pO2-encoded protein,
      towards DNA probes containing either the PE1 sequence or linker-substitution
      mutations in PE1, correlate with the activity of these DNA elements in the rice
      transient expression assay. These mutations are known to abolish expression of a
      reporter gene in vivo. Binding of these linker-substitution mutants to the pO2
      encoded protein in vitro was lower by one to two orders of magnitude than the
      binding of the native PE1 region. We suggest, therefore, that the pO2 clone may
      encode the putative nuclear factor, oat PF1, that is involved in positive
      regulation of PHYA3 by binding to PE1 in vivo. pO2 encodes a 170-amino-acid-long
      protein that contains three repeats of the 'AT-hook' DNA-binding motif found in
      high mobility group I-Y (HMGI-Y) proteins. Oat PF1 is highly similar to rice PF1
      and to the protein encoded by soybean cDNA SB16. They all have a strong
      similarity in their N-terminus to the pea H1 histone, and the presence of several
      AT-hook DNA-binding motifs in their C-terminal halves.

PMID- 7639787
TI  - Developmental dynamics of plant cell-surface glycoproteins: towards a molecular
      plant anatomy.

PMID- 7639788
TI  - Elucidation of phytochrome signal-transduction mechanisms.

PMID- 7639789
TI  - Glycoprotein domains and their role in gamete recognition in Fucus.

PMID- 7639790
TI  - Formation of embryogenic cells in plant tissue cultures.

PMID- 7639791
TI  - Oligosaccharins as plant growth regulators.
AB  - Oligosaccharides with regulatory effects on living plant tissue have been
      obtained by parital hydrolysis of xyloglucan, cellulose and pectic
      polysaccharides. Attention is focused here on xyloglucan-derived oligosaccharides
      (XGOs), which exert the following two distinct effects on cell growth in pea-stem
      segments. (i) At approx. 1 nM, the L-fucosylated XGOs, such as XXFG, XFFG and FG
      (for structure of XXFG, see Fig. 1), antagonize 2,4-dichlorophenoxyacetic acid
      (2,4-D)-stimulated growth. At approx. 100 nM, XXFG loses this growth-inhibitory
      effect, probably because it gains a growth-promoting effect [see (ii)]; in
      contrast, FG retains its growth-inhibitory effect. The growth-inhibitory effect
      is tentatively attributed to membrane-binding of the active XGOs. (ii) At approx.
      1 microM, at least four different cellotetraose-based XGOs (XXXG, XXLG, XXFG and
      XLLG) mimic auxin in that they induce growth. This effect is thus not L-fucose
      dependent and is not exhibited by the cellobiose-based pentasaccharide, FG.
      Effect (ii) is attributed to the ability of cellotetraose-based XGOs to act as
      acceptor substrates for xyloglucan endotransglycosylase. [formula: see text] The
      biosynthesis and biodegradation of relevant XGOs has been investigated. By use of
      labelling with L-[3H]arabinose and L-[3H]fucose in vivo, XXFG and O-acetyl
      derivatives thereof were shown to accumulate extracellularly, in spinach cell
      cultures, to approx. 0.1 microM. The kinetics of labelling of XXFG showed it to
      be formed by degradation of pre-formed polysaccharide rather than by de novo
      synthesis of the oligosaccharide. XXFG was remarkably stable in vivo, undergoing
      little hydrolysis in contact with the surfaces of cultured cells; the major
      metabolic fate of exogenous [3H]XXFG was sequestration into apoplastic
      polysaccharide by endotransglycosylation.

PMID- 7639792
TI  - Lipo-oligosaccharide signalling: the mediation of recognition and nodule
      organogenesis induction in the legume-Rhizobium symbiosis.

PMID- 7639793
TI  - Bacterial and plant glycoconjugates at the Rhizobium-legume interface.
AB  - Many classes of bacterial and plant glycoconjugate have been shown to be involved
      in establishing the Rhizobium root nodule symbiosis with peas (Pisum sativum). It
      was demonstrated, using techniques of molecular genetics, that a group of
      Rhizobium nodulation genes (nod genes) co-operate to synthesize a lipo
      oligosaccharide signal molecule that specifically initiates nodule development on
      legume hosts. An additional gene function, encoded by nodX, has been found to
      extend the host range of Rhizobium leguminosarum bv. viciae to include nodulation
      of a pea mutant, cultivar Afghanistan; the nodX gene product specifies the
      addition of an acetyl group to the terminal N-acetylglucosamine residue at the
      reducing end of the pentasaccharide core of this signal molecule. Several other
      classes of bacterial glycoconjugate have also been shown by genetic analysis to
      be essential for normal nodule development and function: these include a capsular
      extracellular polysaccharide; lipopolysaccharide in the outer membrane; and
      cyclic glucans present in the periplasmic space. Potential functions for these
      glycoconjugates are discussed in the context of tissue and cell invasion by
      Rhizobium. Some plant components involved in symbiotic interactions have been
      identified by the analysis of nodule-specific gene expression (early nodulins).
      Several of the cDNA clones encoding these early nodulins specify proline-rich
      proteins that presumably correspond to cell wall glycoproteins or membrane
      arabinogalactan proteins. Other plant glycoconjugates have been identified using
      monoclonal antibodies as probes. A plant glycoprotein present in intercellular
      spaces has been identified as a component of the luminal matrix of infection
      threads. Because it attaches to the surface of bacteria and is itself susceptible
      to oxidative cross-linking, this glycoprotein may be involved in limiting the
      progress of microbial infections. Endocytosis of bacteria into the plant
      cytoplasm is apparently driven by direct interactions between the bacterial
      surface and the plasma membrane that is exposed within an unwalled infection
      droplet; glycoprotein and glycolipid components of the plant membrane glycocalyx
      have been defined using monoclonal antibodies. Differentiation of endosymbiotic
      bacteroids is preceded by differentiation of the plant-derived peribacteroid
      membrane which encloses the symbiosome compartment. Using a monoclonal antibody
      that identifies a group of plant membrane-associated, inositol-containing
      glycolipids, we have identified a very early marker for the differentiation of
      peribacteroid membrane from plasma membrane.

PMID- 7639794
TI  - Barley-fungal interactions: signals and the environment of the host-pathogen
      interface.

PMID- 7639795
TI  - Oligosaccharins involved in plant growth and host-pathogen interactions.

PMID- 7639796
TI  - Systemic signals condition plant cells for increased elicitation of diverse
      defence responses.

PMID- 7639797
TI  - Measuring relevant change: an emerging challenge in rheumatologic clinical
      trials.

PMID- 7639798
TI  - Levels of circulating collagenase, stromelysin-1, and tissue inhibitor of matrix
      metalloproteinases 1 in patients with rheumatoid arthritis. Relationship to serum
      levels of antigenic keratan sulfate and systemic parameters of inflammation.
AB  - OBJECTIVE: To measure serum levels of matrix metalloproteinase-1 (MMP-1), matrix
      metalloproteinase-3 (MMP-3), and tissue inhibitor of MMP-1 (TIMP-1) in patients
      with rheumatoid arthritis (RA) and in age-matched control subjects, and to
      determine how these correlate with serum levels of antigenic keratan sulfate (KS)
      and other biochemical and clinical indicators of disease activity. METHODS:
      Immunoassays were used to measure levels of MMP-1, MMP-3, TIMP-1, and antigenic
      KS. Radiologic and functional joint scores were based upon Steinbrocker's
      criteria. Erythrocyte sedimentation rates (ESR) and levels of C-reactive proteins
      (CRP) were measured. RESULTS: In RA patients, levels of MMP-3 and TIMP-1 were
      significantly increased, and strongly correlated with the ESR and CRP levels but
      not with radiologic or functional joint scores. Levels of antigenic KS were
      significantly lower in RA patients and correlated negatively with systemic
      parameters of inflammation and serum levels of TIMP-1. CONCLUSIONS: The increase
      in serum levels of MMP-3 and TIMP-1 appears to reflect systemic inflammation in
      RA. The inverse correlation between serum levels of TIMP-1 and antigenic KS
      suggests that an upregulation of TIMP-1 synthesis might be responsible for the
      apparent suppression of cartilage aggrecan catabolism in patients with severe
      inflammatory changes.

PMID- 7639799
TI  - Differential effects of interleukins 10 and 4 on the production of interleukin-6
      by blood and synovium monocytes in rheumatoid arthritis.
AB  - OBJECTIVE: To determine how the antiinflammatory cytokines interleukin-10 (IL-10)
      and IL-4 affect the production of IL-6 in rheumatoid arthritis (RA) and to assess
      the contribution of IL-10 production. METHODS: IL-6 production was measured by
      enzyme-linked immunosorbent assay (ELISA) in the supernatants of cultured RA
      synovium pieces (from 23 patients), purified RA synovial tissue
      monocyte/macrophages, and RA blood monocytes, in the presence of IL-10 and IL-4.
      IL-10 was also detected by ELISA in culture supernatants and in RA sera. RESULTS:
      The production of IL-6 by RA synovium was strongly inhibited by IL-4 (46.6%; P =
      0.0001) and was inhibited to a lower extent by IL-10 (25.3%; P = 0.03). Likewise,
      the spontaneous production of IL-6 by RA synovial tissue monocyte/macrophages was
      decreased by the addition of IL-4 (48.8%) and IL-10 (23.7%). This inhibition of
      IL-6 production was significantly lower (P < 0.03) than that observed with RA
      blood monocytes (83.0% for IL-10 and 85.2% for IL-4). Interestingly, and in
      contrast to RA blood monocytes, RA synovial tissue monocyte/macrophages produced
      spontaneously high levels of IL-10, which were inhibited by IL-4 and interferon
      gamma. CONCLUSION: The ability of IL-10 and IL-4 to suppress IL-6 production was
      dependent on 1) differences in the state of differentiation of blood and synovial
      tissue monocytes, and 2) local production of cytokine inside the synovium.

PMID- 7639800
TI  - Interleukin-1 receptor antagonist in patients with active systemic lupus
      erythematosus. Enhanced production by monocytes and correlation with disease
      activity.
AB  - OBJECTIVE: To evaluate the relationship between the serum concentration of
      interleukin-1 receptor antagonist (IL-1Ra) and systemic lupus erythematosus (SLE)
      disease activity, and to investigate the expression of IL-1Ra messenger RNA
      (mRNA) and its production by monocytes from patients with SLE. METHODS: Serum IL
      1Ra was measured by enzyme-linked immunosorbent assay, and expression of IL-1Ra
      mRNA was determined by Northern blotting. RESULTS: Serum IL-1Ra concentrations
      were significantly higher in patients with active SLE compared with normal
      subjects and patients with other rheumatic diseases, and showed a strong
      correlation with SLE disease activity. IL-1Ra mRNA expression in freshly isolated
      monocytes from patients with active SLE was considerably higher than that in
      normal monocytes. Moreover, monocytes from patients with active SLE produced
      increased amounts of IL-1Ra in response to adherent IgG, compared with monocytes
      from normal subjects. CONCLUSION: A high serum concentration of IL-1Ra is a
      pathophysiologic feature of active SLE and a good indicator of disease activity.
      Functional changes of monocytes, such as increased secretion of IL-1Ra in
      response to adherent IgG and enhanced expression of IL-1Ra mRNA in freshly
      isolated cells, may be involved in the enhanced IL-1Ra production in active SLE.
      High concentrations of IL-1Ra in the circulation and possibly in peripheral
      lymphoid tissues may influence immunologic and inflammatory features of SLE.

PMID- 7639801
TI  - Increased susceptibility to oxidation of low-density lipoproteins isolated from
      patients with systemic sclerosis.
AB  - OBJECTIVE: To examine the resistance to oxidation of low-density lipoproteins
      (LDL) from patients with systemic sclerosis (SSc) and primary Raynaud's
      phenomenon (RP) compared with healthy controls. METHODS: Plasma LDL were isolated
      from patients with diffuse cutaneous and limited cutaneous SSc (dcSSc and lcSSc,
      respectively), patients with primary RP, and healthy control subjects. The
      lipoproteins were assessed for their resistance to oxidation in the presence of
      cupric ions, using spectrophotometric assays. RESULTS: LDL from patients with
      dcSSc and lcSSc were more susceptible to oxidation than were those from healthy
      control subjects or patients with RP. CONCLUSION: Our findings suggest that free
      radicals may play a role in the pathology of SSc.

PMID- 7639802
TI  - A human monoclonal antiphospholipid antibody that is representative of serum
      antibodies and is germline encoded.
AB  - OBJECTIVE: To investigate the origins of antiphospholipid antibodies associated
      with thrombosis and other disorders that are found in patients with systemic
      lupus erythematosus and primary antiphospholipid syndrome (APS). METHODS:
      Characterization, idiotypic study, and nucleotide sequencing of a human
      monoclonal antiphospholipid antibody generated from a patient with primary APS.
      Identification of the germline genes from which the antibody is derived. RESULTS:
      A human monoclonal antibody, BH1, was generated. This antibody has ligand-binding
      properties that closely resemble those of the serum antiphospholipid antibodies
      found in our patient and in other individuals with APS: it recognizes negatively
      charged phospholipids, and has lupus anticoagulant activity; it does not bind to
      neutral phospholipids, or to single-stranded or double-stranded DNA. The
      relevance of BH1 to the patient's serum antibodies is supported by our idiotypic
      studies. BH1 is encoded by a new germline VH gene, and by a lambda light chain
      gene that displays > 99% homology with the V lambda III.1 germline gene.
      CONCLUSION: Serum antiphospholipid antibodies associated with thrombosis may be
      encoded by either germline or only slightly mutated variable-region genes.

PMID- 7639803
TI  - Biased T cell receptor V beta gene usage during specific stages of the
      development of autoimmune sialadenitis in the MRL/lpr mouse model of Sjogren's
      syndrome.
AB  - OBJECTIVE: To analyze the repertoire of T cell receptor (TCR) V beta gene
      transcribed and expressed within the autoimmune lesions of the salivary gland in
      the MRL/lpr mouse model of Sjogren's syndrome. METHODS: Monoclonal antibodies
      (MAb) were used to determine the prevalence of selected V gene elements on T cell
      infiltrates from salivary glands of MRL/lpr mice. To analyze TCR V beta gene
      usage, we used reverse-transcriptase polymerase chain reaction (RT-PCR) and
      single-strand conformational polymorphism (SSCP) analyses. RESULTS: A
      predominance of V beta 8+ T cells was detected within the inflammatory lesions
      during development of autoimmune disease (confirmed by flow cytometry). RT-PCR
      analysis revealed that in autoimmune sialadenitis, the predominant expression of
      the V beta 8 gene segment began in the early stages of disease (2-month-old mice)
      and increased over time. Extensive age-related diversity of TCR V beta gene usage
      was also observed. SSCP analysis demonstrated a distinct and common binding
      pattern of the V beta 8 gene PCR product from the cell infiltrates during the
      course of the disease. CONCLUSION: Our data suggest that in the MRL/lpr mouse
      model of Sjogren's syndrome, there is restricted usage of TCR V beta elements
      according to the stage of the disease, and that V beta 8 are probably used
      preferentially in the recognition of a single unknown self antigen in the
      salivary gland.

PMID- 7639804
TI  - Even low-grade synovitis significantly accelerates the clearance of protein from
      the canine knee. Implications for measurement of synovial fluid "markers" of
      osteoarthritis.
AB  - OBJECTIVE: In recent studies, the synovial fluid concentration of molecules
      derived from the extracellular matrix of articular cartilage has been used to
      deduce the magnitude of cartilage destruction or repair in osteoarthritic (OA)
      joints. Because low-grade synovitis is often present in such joints, we assessed
      the effect of synovial inflammation on the clearance of a prototypical protein,
      albumin, from synovial fluid. METHODS: 131I-labeled albumin (RISA) was injected
      into 1 (control) knee of each of 14 dogs. The concentration of RISA in synovial
      fluid aspirated 7 hours after the injection and serial measurements of surface
      radioactivity were used to calculate the volume of distribution (Vd) and
      clearance of RISA. One week later, synovitis was induced in the contralateral
      knee by intraarticular injection of various quantities of calcium pyrophosphate
      dihydrate (CPPD) crystals, after which RISA was injected into that joint and
      these measurements were repeated. RESULTS: Intraarticular injection of 500
      micrograms of CPPD crystals produced intense synovitis, with a mean synovial
      fluid white blood cell (WBC) count of 43,200 cells/mm3, and values for RISA Vd
      and RISA clearance (36.5 ml and 33.7 microliters/minute) were much higher than
      those for saline-injected control knees (2.7 ml and 1.5 microliters/minute,
      respectively). Injection of 0.5 microgram of CPPD also produced marked synovitis
      and values for Vd and RISA clearance that were 2-3-fold greater than those in the
      contralateral knee. The low-grade synovitis produced by only 0.05 microgram of
      CPPD, which resulted in synovial fluid WBC counts as low as 1,000-2,000
      cells/mm3, was accompanied by increases in the clearance and Vd of RISA to levels
      approximately 40% and approximately 80% higher, respectively, than those for the
      contralateral knee. CONCLUSION: Even mild synovitis, as seen in OA, may
      significantly increase the clearance of a protein from the joint. Synovitis is a
      significant variable which must be considered in studies of putative
      chondroprotective drugs if conclusions about the effects of drugs on cartilage
      metabolism are to be drawn from changes in the synovial fluid concentration of a
      "marker" protein.

PMID- 7639805
TI  - Suppression of antigen-induced arthritis in Lewis rats by oral administration of
      type II collagen.
AB  - OBJECTIVE: To assess the effect of orally administered type II collagen (CII) in
      antigen-induced arthritis (AIA). METHODS: Arthritis was induced in Lewis rats by
      immunization with methylated bovine serum albumin (mBSA) in Freund's complete
      adjuvant, followed by an intraarticular injection of mBSA 2 weeks later.
      Different doses of CII, mBSA, and an unrelated control protein, keyhole limpet
      hemocyanin (KLH), were orally administered 5 times over several days prior to the
      induction of arthritis. Ankle joint swelling and delayed-type hypersensitivity
      (DTH) responses were measured. RESULTS: Joint swelling was significantly reduced
      at a dose of 3 micrograms and 30 micrograms of CII, but not at 300 micrograms.
      The most prominent suppression of AIA was observed when rats were fed 10 mg of
      mBSA, whereas oral KLH had no effect. DTH responses were significantly reduced in
      the mBSA-fed rats, but not in rats that were fed CII or KLH. CONCLUSION: Oral CII
      can suppress arthritis in an animal model in which immunity to collagen does not
      play a role. The effect is dose dependent and occurs at lower doses of CII. These
      results demonstrate the biologic relevance of bystander suppression associated
      with oral tolerance, and the potential use of this approach to treat human
      inflammatory joint disease.

PMID- 7639806
TI  - A randomized, double-blind, placebo-controlled study of CD4 monoclonal antibody
      therapy in early rheumatoid arthritis.
AB  - OBJECTIVE: To assess the efficacy of the CD4 monoclonal antibody (MAb) cM-T412 in
      the treatment of early rheumatoid arthritis (RA). METHODS: Sixty patients were
      enrolled in a 6-week randomized, double-blind, placebo-controlled study
      investigating multiple dose regimens of cM-T412. Thirty patients subsequently
      were enrolled in a 9-month randomized, double-blind, placebo-controlled study
      investigating monthly single-dose administrations of cM-T412. RESULTS: Analysis
      of clinical parameters revealed no changes in arthritis activity in the groups
      that received CD4 MAb or the placebo group, and no difference between the groups,
      in either in the first or the second part of the study. The number of circulating
      CD4+ cells decreased substantially in the patients treated with CD4 MAb.
      CONCLUSION: CD4 MAb treatment of patients with early RA induced no therapeutic
      effect.

PMID- 7639807
TI  - Effects of high-dose fish oil on rheumatoid arthritis after stopping nonsteroidal
      antiinflammatory drugs. Clinical and immune correlates.
AB  - OBJECTIVE: To determine the following: 1) whether dietary supplementation with
      fish oil will allow the discontinuation of nonsteroidal antiinflammatory drugs
      (NSAIDs) in patients with rheumatoid arthritis (RA); 2) the clinical efficacy of
      high-dose dietary omega 3 fatty acid fish oil supplementation in RA patients; and
      3) the effect of fish oil supplements on the production of multiple cytokines in
      this population. METHODS: Sixty-six RA patients entered a double-blind, placebo
      controlled, prospective study of fish oil supplementation while taking diclofenac
      (75 mg twice a day). Patients took either 130 mg/kg/day of omega 3 fatty acids or
      9 capsules/day of corn oil. Placebo diclofenac was substituted at week 18 or 22,
      and fish oil supplements were continued for 8 weeks (to week 26 or 30). Serum
      levels of interleukin-1 beta (IL-1 beta), IL-2, IL-6, and IL-8 and tumor necrosis
      factor alpha were measured by enzyme-linked immunosorbent assay at baseline and
      during the study. RESULTS: In the group taking fish oil, there were significant
      decreases from baseline in the mean (+/- SEM) number of tender joints (5.3 +/-
      0.835; P < 0.0001), duration of morning stiffness (-67.7 +/- 23.3 minutes; P =
      0.008), physician's and patient's evaluation of global arthritis activity (-0.33
      +/- 0.13; P = 0.017 and -0.38 +/- 0.17; P = 0.036, respectively), and physician's
      evaluation of pain (-0.38 +/- 0.12; P = 0.004). In patients taking corn oil, no
      clinical parameters improved from baseline. The decrease in the number of tender
      joints remained significant 8 weeks after discontinuing diclofenac in patients
      taking fish oil (-7.8 +/- 2.6; P = 0.011) and the decrease in the number of
      tender joints at this time was significant compared with that in patients
      receiving corn oil (P = 0.043). IL-1 beta decreased significantly from baseline
      through weeks 18 and 22 in patients consuming fish oil (-7.7 +/- 3.1; P = 0.026).
      CONCLUSION: Patients taking dietary supplements of fish oil exhibit improvements
      in clinical parameters of disease activity from baseline, including the number of
      tender joints, and these improvements are associated with significant decreases
      in levels of IL-1 beta from baseline. Some patients who take fish oil are able to
      discontinue NSAIDs without experiencing a disease flare.

PMID- 7639808
TI  - Usefulness of the American College of Rheumatology recommendations for liver
      biopsy in methotrexate-treated rheumatoid arthritis patients.
AB  - OBJECTIVE: To test the usefulness and cost savings resulting from application of
      the new American College of Rheumatology (ACR) guidelines for assessing the risk
      for the development of clinically significant liver disease in rheumatoid
      arthritis (RA) patients treated with methotrexate (MTX). METHODS: One-hundred
      twelve MTX-treated RA patients were prospectively followed up for MTX
      hepatotoxicity and underwent liver biopsies according to modified guidelines of
      the Psoriatic Task Force (PTF). All biopsies were graded according to the Roenigk
      classification. The new ACR recommendations were then retrospectively applied to
      test their usefulness and cost-effectiveness in this cohort. RESULTS: Based on
      the PTF guidelines, 66 patients underwent liver biopsies; a total of 110 liver
      biopsies were performed. Two patients had biopsy-related complications. Five
      patients were found to have Roenigk grade IIIB or IV histologic abnormalities.
      The total cost for this group was $111,380. Applying the new ACR criteria, only
      15 patients would have undergone liver biopsies; there would have been a total of
      18 biopsies, with no complications. Four of the 5 patients with Roenigk grade
      IIIB or IV liver abnormalities would have been identified. One patient with
      insulin-dependent diabetes mellitus (IDDM) who was found to have cirrhosis
      (Roenigk grade IV) on liver biopsy as a result of use of the PTF guidelines would
      have been missed with use of the ACR guidelines. The total cost for the group
      receiving biopsies based on the ACR guidelines would have been $16,956. Overall,
      the new ACR guidelines had 80% sensitivity and 82% specificity and resulted in a
      cost savings of $1,430 per patient. CONCLUSION: The new ACR guidelines on MTX
      monitoring and biopsy surveillance appear to be clinically useful and result in
      considerable cost savings. However, 1 IDDM patient with significant liver
      histologic abnormalities would have been missed. We suggest that IDDM be added to
      the ACR guidelines as a risk factor for MTX hepatotoxicity.

PMID- 7639809
TI  - Effects of cyclophosphamide on the development of malignancy and on long-term
      survival of patients with rheumatoid arthritis. A 20-year followup study.
AB  - OBJECTIVE: To examine the effects of cyclophosphamide (CYC) on the development of
      malignancies and on the long-term survival of patients with rheumatoid arthritis
      (RA). METHODS: We used a longitudinal cohort design in which 119 patients (76
      women and 43 men) with refractory RA who were treated with oral CYC between 1968
      and 1973 were compared with 119 control patients with RA (matched for age, sex,
      disease duration, and functional class) who were evaluated during the same time
      period but did not receive CYC. RESULTS: There was increased risk of malignancy
      in the CYC-treated group, with 50 cancers found in 37 patients in the CYC group
      compared with 26 cancers in 25 of the control patients (P < 0.05). The relative
      risk of cancer for those treated with CYC was 1.5 (95% confidence interval 0.93
      5.5). Nine of the malignancies in the CYC group were bladder cancers and 19 were
      skin cancers, compared with no bladder cancers and 6 skin cancers in the control
      group. The total dose of CYC was higher in those who developed cancer,
      particularly in those with bladder cancer. Three of the bladder cancers occurred
      14, 16, and 17 years after CYC had been discontinued. CONCLUSION: The risk of
      malignancy, particularly bladder cancer, in RA patients treated with oral CYC
      continues even 17 years after discontinuation of the drug.

PMID- 7639810
TI  - Access to medical care among persons with musculoskeletal conditions. A study
      using a random sample of households in San Mateo County, California.
AB  - OBJECTIVE: To study access to medical care services, including subspecialty care,
      among persons with musculoskeletal conditions. METHODS: In early 1993, a random
      sample of households in San Mateo County, California, was screened for the
      presence of household members with musculoskeletal conditions, and a member of
      each household so identified was administered a structured survey about access to
      medical care and other related subjects. RESULTS: Eighty-six percent of all
      persons with a musculoskeletal condition had ever seen at least one physician for
      the condition, but only 6.5% had ever seen a rheumatologist. Those without health
      insurance were only 82% as likely as those with health insurance to have ever
      seen a physician. CONCLUSION: Most persons with a musculoskeletal condition have
      seen a physician for the condition, but lack of health insurance significantly
      reduces the proportion who have done so.

PMID- 7639811
TI  - Incidence of symptomatic hand, hip, and knee osteoarthritis among patients in a
      health maintenance organization.
AB  - OBJECTIVE: To quantify the incidence of symptomatic hand, hip, and knee
      osteoarthritis (OA) among members of the Fallon Community Health Plan, a health
      maintenance organization located in central Massachusetts. METHODS: Incident OA
      was defined as the first evidence of OA by radiography (grade > or = 2 on the
      Kellgren-Lawrence scale of 0-4) plus joint symptoms at the time the radiograph
      was obtained or up to 1 year before the radiograph was obtained. RESULTS: The age
      and sex-standardized incidence rate for hand OA was 100/100,000 person-years
      (95% confidence interval [95% CI] 86, 115), for hip OA 88/100,000 person-years
      (95% CI 75, 101), and for knee OA 240/100,000 person-years (95% CI 218, 262). The
      incidence of hand, hip, and knee OA increased with age, and women had higher
      rates than men, especially after age 50. A leveling off or decline occurred for
      both groups around the age of 80. CONCLUSION: In a large study of symptomatic OA
      we observed incidence rates that increased with age. In women ages 70-89, the
      incidence of knee OA approached 1% per year.

PMID- 7639812
TI  - Development of an observation method for assessing pain behaviors in children
      with juvenile rheumatoid arthritis.
AB  - OBJECTIVE: To develop an observation method for assessing pain behaviors in
      children with juvenile rheumatoid arthritis (JRA). METHODS: Thirty children with
      JRA performed a standardized sequence of activities for video recording, and
      correlations between the pain behaviors observed on the videotapes and
      established measures of pain, depression, and functional disability were
      determined. RESULTS: Pain behaviors were reliably observed (kappa coefficients
      0.53-0.79). Total pain behaviors were significantly correlated with subjective
      reports of pain (r = 0.50) and disability levels (r = 0.64). These behaviors were
      not significantly associated with children's depression ratings (r = 23).
      CONCLUSION: The results indicate that the behavioral observation method provides
      a reliable and valid measure of pain associated with JRA. Measurement of pain
      behaviors may be especially useful in treatment outcome studies because these
      behaviors are relatively independent of depression.

PMID- 7639813
TI  - Photoexacerbation of cutaneous lupus erythematosus due to ultraviolet A emissions
      from a photocopier.
AB  - This report describes a woman with systemic lupus erythematosus (LE) who worked
      as a photocopy technician and developed cutaneous LE of the hands, neck, face,
      and chest. Her skin lesions improved when she discontinued her employment.
      Testing of several photocopy devices showed emission of small quantities of
      ultraviolet A (UVA), but no UVB. Phototesting of the patient with UVA and UVB
      induced skin lesions that were clinically and histopathologically consistent with
      LE. Thus, the action spectrum of cutaneous LE may be within the UVB range, the
      UVA range, or both ranges of the solar spectrum, and repeated exposure to short
      bursts of light may induce clinical disease. This case suggests that occupational
      sources of UV light should be considered as possible exacerbating factors in LE.

PMID- 7639814
TI  - Lyme disease in a 74-year-old forest owner with symptoms of dermatomyositis.
AB  - We describe a 73-year-old forest owner with widespread erythema, myalgia, and
      proximal muscle weakness. The clinical signs and the results of electromyography,
      magnetic resonance imaging, and a muscle biopsy were consistent with
      dermatomyositis. However, serology was positive for Borrelia burgdorferi. More
      importantly, B burgdorferi DNA was detected in skin by polymerase chain reaction
      techniques, and spirochete-like organisms were detected in the muscle by silver
      staining. Lyme disease with muscle involvement can mimic or trigger
      dermatomyositis and should be considered in the differential diagnosis of
      dermatomyositis.

PMID- 7639815
TI  - Fever, arthralgias, skin lesions, and ischemic digits in a 59-year-old man.

PMID- 7639816
TI  - The American Board of Internal Medicine recertification program in rheumatology.

PMID- 7639817
TI  - T cell epitope mapping of U1-A RNP.

PMID- 7639818
TI  - Effect of patient population characteristics in assessing the efficacy and
      toxicity of methotrexate in rheumatoid arthritis: comment on the article by
      Weinblatt et al.

PMID- 7639819
TI  - Association of Wegener's granulomatosis with parvovirus B19 infection: comment on
      the concise communication by Nikkari et al.

PMID- 7639821
TI  - [Validity of the clinical diagnosis with autopsy].

PMID- 7639820
TI  - [The piriformis muscle syndrome due to pyomyositis].

PMID- 7639822
TI  - [Fatal cocaine poisoning].

PMID- 7639823
TI  - [Malaria after diethylcarbamazine].

PMID- 7639824
TI  - [The validation of a rapid diagnostic method for urinary infection in the school
      age population].
AB  - Validity of visual reading of a reactive strip is measured, in comparison with
      automatized reading and the exam of the urinary sediment, in 562 school pupils
      with ages between 6 and 16 years. Using urine culture as standard reference,
      sensibility of the leukocyte-esterase (L-E) test, nitrites and red cells was
      66.7%, 33.3% and 66.7% respectively, for the visual reading; 66.7%, 33.3% and
      33.3% for automatized reading, respectively; and 66.7% for leukocyturia, and
      33.3% for hematuria in the urine sediment. Specificity of tests was 84.9%, 99%
      and 42.7% for L-E, nitrites and red cells, in visual reading; 92.5%, 100% and
      80.8% for the same tests in automatized reading, and 94.5% (leukocyturia) and
      86.3% (red cells) in the urinary sediment. Validity of these diagnostic methods
      results different depending on the population they are applied to. Even though
      the multi-urine test is still the most effective test in a symptomatic population
      and the less expensive, it would be not recommendable its use as a screening test
      in a school population with hidden urinary infection.

PMID- 7639825
TI  - Effects of pethidine, acetylsalicylic acid, and indomethacin on pain and behavior
      in the mole-rat.
AB  - The antinociceptive and behavioral effects of pethidine (10, 20, or 30 mg/kg),
      acetylsalicylic acid (200, 400, or 600 mg/kg) and indomethacin (20, 40, or 50
      mg/kg) in the naked mole-rat was studied in the hot-plate test. Instead of
      inducing analgesia, pethidine caused a dose-dependent reduction in response
      latency. Sensorimotor impairment and aggressive behavior were also observed
      following administration of pethidine (20 or 30 mg/kg). All animals receiving
      pethidine (30 mg/kg) died following fighting when kept in colony cages.
      Aggressive behavior and death was prevented by naloxone or by keeping animals in
      single cages. Acetylsalicylic acid (600 mg/kg) and indomethacin (40 or 50 mg/kg)
      caused a significant increase in response latency. It is concluded that in the
      mole-rat pethidine elicits aggression, sensorimotor impairment, and apparent
      hyperalgesia.

PMID- 7639827
TI  - [Transient thrombus in patent foramen ovale with pulmonary and paradoxical
      embolization].
AB  - Ten days after surgical treatment of a gastric perforation a 70-year-old woman
      developed progressive dyspnoea and hypertension without any signs of deep vein
      thrombosis. Emergency echocardiography revealed acute cor pulmonale with a
      dilated right atrium and ventricle, as well as paradoxical ventricular septal
      motion. In addition it demonstrated an elongated, extremely mobile thrombus stuck
      in a patent foramen ovale with most of it floating in the right atrium, the
      remainder in the left atrium. Within 2 hours of the ultrasound examination she
      went into fulminant pulmonary embolism with circulatory arrest and paradoxical
      embolization from the atria to the brain, after which the intraatrial thrombus
      was no longer detectable. She was successfully resuscitated and thrombolysis was
      immediately started with tissue-plasminogen activator (100 mg over 90 min), with
      ensuing stabilization of the circulation. The patient was gradually weaned off
      the ventilator over the following few days, but she died 10 days after the
      resuscitation from the severe cerebral damage.

PMID- 7639826
TI  - [Comment on the contribution by B. Stuck. Vaccination--in legal compliance and of
      free will].

PMID- 7639828
TI  - [Is laparoscopy helpful in acute appendicitis?].

PMID- 7639829
TI  - [In search of a second opinion].

PMID- 7639830
TI  - [Overdiagnosis of cervix cancer. Increasing anxiety of patients and more
      expensive health care services].

PMID- 7639831
TI  - [Cost-effective treatment with ondansetron].

PMID- 7639832
TI  - [A FEM (Finite-Element-Measurement) study for the biomechanical comparison of
      labial and palatal force application on the upper incisors].

PMID- 7639833
TI  - [Is cannabis always a soft drug?].

PMID- 7639834
TI  - [Is laparoscopy of value in acute appendicitis?].

PMID- 7639835
TI  - [Financing of health care research. The pharmaceutical industry].

PMID- 7639836
TI  - [Synovial reaction in rheumatoid arthritis].

PMID- 7639837
TI  - [Effect of district psychiatry on admission and ambulatory treatment].

PMID- 7639838
TI  - Non-isotopic labeling of DNA by newly developed hapten-containing platinum
      compounds.
AB  - A newly developed reagent was tested for its applicability in in situ
      hybridization and in reversed hybridization of DNA fragments generated by PCR
      amplification. This Platinum-complex, designated universal linkage system (ULS),
      equipped, for instance, with biotin or fluorescein as hapten, enables versatile
      nonenzymatic "one step" labeling of genomic, cloned or amplified DNA. Here we
      demonstrate direct in situ detection of integrated human papilloma virus (HPV)
      DNA in cervical carcinoma cells using DNA probes labeled with fluorescein-ULS. In
      cervical smears the presence of HPV or Chlamydia trachomatis was assessed by PCR.
      To analyze the amplified DNA, a reversed hybridization assay was developed.
      Immobilized probes were incubated with amplimers that were labeled post
      amplification through the action of the biotinylated (BIO)-ULS complex. This
      novel type of nonradioactive analysis appeared to be as sensitive as its isotopic
      or colorimetric equivalents. This labeling procedure is simple, versatile and can
      be included as a universal hapten linkage system in any PCR test or in situ
      hybridization assay aiming at the detection and identification of DNA or RNA
      molecules.

PMID- 7639839
TI  - [Internal medicine and medical specialties].

PMID- 7639840
TI  - [Visit to the day surgery unit of the Addenbrooke Hospital].

PMID- 7639841
TI  - [Female gender and mortality following acute myocardial infarction].

PMID- 7639842
TI  - [Colchicine in gout: yes or no?].

PMID- 7639843
TI  - A matched cohort study of planned home and hospital births in Western Australia
      1981-1987.
AB  - OBJECTIVE: to evaluate practice comparing planned home birth with planned
      hospital birth DESIGN: a retrospective analysis of a cohort who had planned to
      have a home birth compared with a matched hospital birth group SETTING: Western
      Australia (WA) PARTICIPANTS: all women (N = 976) who 'booked' to have a home
      birth 1981-1987 and 2928 matched women who had a planned hospital birth
      (singleton births only). MEASUREMENTS AND FINDINGS: women in the home birth group
      had a longer labour, were less likely to have had labour induced or to have had
      any sort of operative delivery. They were less likely overall to have had
      complications of labour, but more likely to have had a postpartum haemorrhage and
      more likely to have had a retained placenta. Babies in the home birth group were
      heavier and more likely to be post-term. They were less likely to have had an
      Apgar score below 8 at 5 minutes, to have taken more than 1 minute to establish
      respiration or to have received resuscitation. The crude odds ratio for planned
      home births for perinatal mortality was 1.25 (95% CI 0.44-3.55). Postneonatal
      mortality was more common in the hospital group. Planned home births were
      generally associated with less intervention than hospital births and with less
      maternal and neonatal morbidity, with the exception of third stage complications.
      Although not significant, the increase in perinatal mortality has been observed
      in other Australian studies of home births and requires continuing evaluation.
      KEY CONCLUSIONS: Planned home births in WA appear to be associated with less
      overall maternal and neonatal morbidity and less intervention than hospital
      births. IMPLICATIONS FOR PRACTICE: whether these observed differences in
      intervention and morbidity have any relationship to the small, non-significant
      increase in perinatal mortality could not be determined in this study. Continuing
      evaluation of home birth practice and outcome is essential.

PMID- 7639844
TI  - Direct DNA sequencing of PCR-amplified vector inserts following enzymatic
      degradation of primer and dNTPs.

PMID- 7639845
TI  - Gene synthesis, high-level expression, and mutagenesis of Thiobacillus
      ferrooxidans rusticyanin: His 85 is a ligand to the blue copper center.
AB  - An artificial gene of the blue copper protein rusticyanin from Thiobacillus
      ferrooxidans was constructed from eight overlapping oligonucleotides in a
      recursive "one-pot" polymerase chain reaction. The gene was placed behind the
      T7/lacOR promoter of pET24a and expressed in Escherichia coli as a soluble
      protein. A purification scheme involving a pH titration step, cation-exchange
      chromatography, and reverse-phase HPLC separation provided yields of the
      apoprotein ranging from 70 to 100 mg/L of cell culture; reconstitution with
      Cu(II) is quantitative at pH 3.4-5.5. The redox reactions and the electronic
      absorption and EPR spectra of the recombinant Cu(II)-rusticyanin and NMR spectra
      of the reduced holoprotein are indistinguishable from those of the protein
      derived from T. ferrooxidans. Rusticyanin possesses the phylogenetically
      conserved carboxy-terminal loop of three copper ligands (Cys 138, His 143, and
      Met 148), but the identity of the fourth ligand was not clear from sequence
      homology to other blue copper proteins. To address this question directly, we
      have prepared two site-specific mutants where two of the proposed ligands, Asp 73
      and His 85, have been replaced with alanine. The Asp73Ala mutant retained the
      electronic properties of the wild-type blue copper center (absorption maxima at
      452, 597, and 750 nm), whereas the His85Ala variant gave rise to a green type 1
      copper protein (absorption maxima at 455 and 618 nm).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7639846
TI  - Making routine data adequate to support clinical audit.

PMID- 7639847
TI  - Response to the letter of Sheldon Wolff (Radiat. Res. 141, 230-231, 1995)

PMID- 7639848
TI  - Prevention of spontaneous tumours in female rats by fadrozole hydrochloride, an
      aromatase inhibitor.
AB  - Mammary tumours are oestrogen dependent in female Sprague-Dawley rats and in a
      significant proportion of women, so pharmacological treatment to inhibit
      oestrogen production is a valuable therapeutic measure to prevent or slow the
      progression of disease. Here we show that a non-steroidal aromatase inhibitor,
      which competitively inhibits the conversion of androstenedione to oestrone,
      prevents the development of both benign and malignant spontaneous mammary
      neoplasms in female Sprague-Dawley ats. It also slows the spontaneous development
      of pituitary pars distalis adenomas in female rats, and reduces the incidence of
      spontaneous hepatocellular tumours in male and female rats.

PMID- 7639849
TI  - Low level quantification of cholesteryl ester transfer protein in plasma
      subfractions and cell culture media by monoclonal antibody-based immunoassay.
AB  - Sensitive immunoradiometric (IRMA) and ELISA assays for cholesteryl ester
      transfer protein (CETP) have been developed using two different monoclonal
      antibodies (MAbs). The MAbs were prepared against human plasma CETP and
      demonstrated specificity by their inhibition of cholesteryl ester transfer
      activity and by immunoblots of crude plasma fractions and whole media from
      transfected CHO cells. For these sandwich-type assays, one MAb, 2F8, is used for
      capture, and the second MAb, 2E7, is iodinated (IRMA) or conjugated with alkaline
      phosphatase (ELISA) and used for detection. Both assays are linear and provide
      sensitivities much greater than previously reported. The IRMA allows for the
      accurate quantification of CETP in the range of 0.5-20 ng/assay (5-200 ng/ml),
      the ELISA 0.05-5 ng/assay (0.5-50 ng/ml). Using the IRMA, the mean plasma CETP
      concentration in 44 normolipidemic individuals was determined to be 2.10 +/- 0.36
      micrograms/ml; 2.05 +/- 0.33 for males (n = 25) and 2.16 +/- 0.40 for females (n
      = 19). Values ranged from 1.28 to 2.97 micrograms/ml and CETP mass correlated
      well with cholesteryl ester transfer activity (r = 0.913, n = 23). The
      distribution of CETP in human plasma was examined both by gel permeation fast
      protein liquid chromatography (FPLC) and by native gel electrophoresis. For FPLC
      using agarose resins, a low ionic strength, isotonic buffer system resulted in
      near total recoveries of CETP, and demonstrated a peak for CETP mass centered at
      molecular masses of 150 to 180 kilodaltons, larger than that for free monomeric
      CETP. Native acrylamide gel electrophoresis of plasma from six individuals,
      followed by 2F8/2E7 sandwich immunoblotting, showed CETP migrating within a size
      range of 170-220 kilodaltons. This result is consistent with suggestions that
      plasma CETP is associated with small-sized HDL. Agarose gel electrophoresis
      showed plasma CETP, as well as purified recombinant CETP, to be prebeta
      migrating. For determining the concentration of CETP in the media of cultured
      HepG2 cells, advantage was taken of the high sensitivity of the ELISA. CETP
      levels were found to increase linearly over the 100-h culture period, reaching
      8.0 +/- 0.4 ng/ml (18.0 +/- 1.3 ng/mg cell protein). These sensitive, direct
      immunoassays for CETP mass should be valuable aids for examining the behavior of
      CETP in plasma and other complex systems, as well as for studying the synthesis
      and secretion of CETP by different cells and tissues.

PMID- 7639850
TI  - [Quality assurance in pathologic anatomy and cytology].

PMID- 7639851
TI  - [To study protein p53. Why, how?].

PMID- 7639852
TI  - [Transgenic mice, animal models of human diseases].

PMID- 7639853
TI  - [The tumor suppressor gene p53 (part one). Structure, function and mechanisms of
      inactivation].

PMID- 7639854
TI  - [The tumor suppressor gene p53 (part 2). Applications in human pathology].

PMID- 7639855
TI  - [Immunocytochemical analysis of human prolactin receptors using anti-idiotypic
      antibodies in human breast cancer].
AB  - In this study, we have prepared antiidiotypic antibodies specific of human
      prolactin receptors (PRL-R) in order to localize these receptors in breast
      cancer. Antiidiotypic antibodies were prepared using anti-human prolactin (anti
      hPRL) sera obtained from New Zealand rabbits. 25 breast cancer were PRL-R
      positive using radio receptor assay. For immunohistochemistry, the tissues fixed
      with Nakane and treated by NH4Cl and Saponin to improve staining specificity,
      were incubated with antiidiotypic antibodies (1/100e). Cytoplasm and membrane of
      human breast cancer cells were PRL-R positive in 20/25 breast cancer with
      antiidiotypic antibodies. There was no staining with preimmune serum and
      immunohistochemical staining elimination by prior absorption with anti-hPRL
      antibodies.

PMID- 7639856
TI  - [Histologic and immunohistochemical profiles of benign granular cell tumors.
      Report of 41 cases].
AB  - Since the descriptions of << myoblastomas >>, later denominated granular cell
      tumours, many immunohistological and ultrastructural studies have been undertaken
      with the aim of establishing their histogenesis. Now the hypothesis of a
      neurogenic origin appears clear. From the large number of cases (53) diagnosed in
      Geneva over a period of 10 years, we decided to do a retrospective study of these
      tumours with regard to their immunohistological phenotypes, using the following
      markers: S100 protein (S100), Neuron specific enolase (NSE), Vimentin,
      Chromogranin, Glial fibrillary acidic protein (GFAP), Keratin, Epithelial
      membrane antigen (EMA), Desmin, Smooth muscle alpha actin. 100% of tumours were
      positive for S100, and 90% for NSE, which confirms the neurogenic origin. 70%
      were Vimentin positive, with however a variable intensity. All the other markers
      were negative. Immunohistological staining for S100 and NSE may be useful tool in
      the diagnosis of these tumours.

PMID- 7639857
TI  - [Primary synovial sarcoma of the mediastinum. A case report with
      immunohistochemistry, ultrastructural and cytogenetic study].
AB  - A biphasic synovial sarcoma occurring in the anterior and inferior mediastinum in
      a 19-year-old woman is reported. A biopsy showed a mesenchymal proliferation and
      the tumor was first misdiagnosed as a hemangiopericytoma. Inefficacy of
      chemotherapy led to a tumorectomy. Histologic and immunohistochemical studies on
      multiple samples showed a biphasic tumor. Ultrastructural study confirmed the
      presence of epithelial elements and cytogenetic analysis disclosed a
      translocation t(X;18) (p11;q11), leading to a diagnosis of synovial sarcoma.
      Synovial sarcoma of the mediastinum is very rare and to our knowledge has not
      been previously studied with the help of cytogenetics. Given the biphasic pattern
      of the tumor and its mediastinal location, it can be confused with mesothelioma.
      This stresses the interest of chromosome analysis in the study of tumors
      histologically difficult to classify.

PMID- 7639858
TI  - [Inflammatory myofibroblastic tumor of the lung with endobronchial, infiltrating,
      multifocal and recurrent form].
AB  - Pulmonary inflammatory myofibroblastic tumor (inflammatory pseudotumor, plasma
      cell granuloma) was reported most often as a single peripheral mass, successfully
      cured by surgery. A 14-year-old girl presented with a large left pulmonary mass
      involving and obliterating the main bronchus; there were angioinvasion and
      infiltration of mediastinum, hilar lymph nodes and pleura. Multiple, often tiny
      nodules were seen in the right lung. At microscopic examination, there were
      lymphocytic and plasmacytic infiltrates and borderline myofibroblastic
      proliferation with focal nuclear anaplasia. Smaller lesions were similar to
      organizing pneumonia. Disease was progressive in the remaining right lung after
      surgical resection and a two-month treatment with corticoids. The patient was
      then treated with chemotherapy. She was alive and well (twenty-month follow-up).

PMID- 7639859
TI  - [Adenocarcinoma of Brunner's glands: an entity exceptionally described. Report of
      a case].
AB  - The authors report two cases of adenocarcinoma arising from Brunner's glands. The
      diagnosis was made on histological, histochemical and lectin-histochemical
      grounds. Brunner's glands carcinoma cells were alike and located very close to
      normal Brunner's glands. Brunner's glands carcinoma cells contained neutral
      glycoproteins and were positive for Concanavalin A.

PMID- 7639860
TI  - [A case of post-traumatic uveitis].

PMID- 7639861
TI  - [Cerebrovascular accidents of unusual etiology and fatal course].

PMID- 7639862
TI  - [Guidelines for the diagnosis of endocarditis. Pathology of the cardiac valves].
AB  - This article reports the difficulties of the diagnosis of endocarditis,
      especially when blood cultures are negative. It emphasizes the respective roles
      of the microbiology and pathology laboratories for the processing of cardiac
      valves removed by surgery. It clarifies the morphological characteristics of the
      endocarditis.

PMID- 7639863
TI  - [Reversible pulmonary overload with clofazimine (Lamprene) in HIV-positive
      subjects].

PMID- 7639864
TI  - [Histologic classification of bone tumors (WHO 1993)].

PMID- 7639865
TI  - Statistical issues in the design of HIV vaccine trials.
AB  - HIV vaccine trials present significant challenges related to trial endpoints,
      vaccine efficacy measurement, and the role of nonvaccine interventions. Infection
      is a valid endpoint for detecting sterilizing immunity. But if the vaccine
      prevents AIDS without preventing infection, infection may be a misleading
      surrogate. Appropriate endpoints must be defined for other mechanisms of vaccine
      action. Direct, indirect, behavioral, and biological effects all determine
      vaccine efficacy. False security among HIV-vaccine recipients may make negative
      behavioral effects an important component of vaccine performance. Both biological
      potency and a more comprehensive program effectiveness should be measured. These
      goals may require unblinded designs or community randomization. Nonvaccine
      interventions are currently the only HIV-prevention strategy. Support for larger
      scale implementation requires more rigorous evaluation that is less dependent on
      self-reported behavioral changes. The vaccine trial cohorts provide a unique
      opportunity to cost-effectively evaluate behavioral interventions.

PMID- 7639866
TI  - The importance of human exposure information: a need for exposure-related data
      bases to protect and promote public health.
AB  - As a subfield of public health, environmental health is concerned with evaluating
      and ameliorating the effects of people on the environment and the effects of the
      environment on people. Separating hazards from risks, and characterizing the
      magnitude, likelihood, and uncertainty of risks is at the heart of environmental
      health in the 1990s. To this end, a full range of data is needed, including data
      that characterize the distribution of hazards, the population potentially at
      risk, and the contact between people and pollution that creates the risk. Several
      government-sponsored data systems contain information on a range of exposure
      estimators. The challenge is to develop meaningful, properly validated models to
      identify public health needs and evaluate public health programs.

PMID- 7639867
TI  - Microbial contamination of shellfish: prevalence, risk to human health, and
      control strategies.
AB  - There has been significant concern in recent times about the safety of molluscan
      shellfish for human consumption. Despite extensive efforts to assure a safe
      supply of molluscan shellfish, the number of cases of disease and death are still
      great enough to cause concern among the public. The number of cases of illness
      and death associated with the ingestion of shellfish falls in the lower end of
      the range of other similar microbial pathogen-related foodborne disease. Disease
      and deaths due to viruses and naturally occurring bacteria are now of greatest
      concern because they are the most often cited causative agents. The greatest risk
      of disease or death due to shellfish consumption is among the population with
      underlying health conditions who choose to consume raw shellfish. Control
      strategies to limit shellfish-borne disease should focus upon disease and death
      caused by viruses and naturally occurring bacteria among at-risk populations.

PMID- 7639868
TI  - Infectious risks for health care workers.
AB  - Although health care has been practiced for eons and although hundreds of
      thousands of workers are engaged in it, we know distressingly little about ways
      to prevent work-related infectious illnesses in this important group. Assumptions
      may be dangerous and expensive: Are "universal precautions" effective; when are
      respirators necessary? These kinds of questions have taken on particular urgency
      in the face of multiple-drug resistant tuberculosis and the spread of human
      immunodeficiency virus and other blood-borne pathogens. Furthermore, health care
      has moved from the traditional hospital setting into ambulatory, home, and other
      noninstitutional settings, thus increasing the complexity of worker protection
      measures. Steps to ensure the safety and health of health care workers must
      therefore include research and action that lead to identifying workers at risk;
      planning; education; providing necessary equipment and assuring adequate
      staffing; using appropriate techniques and precautions; immunizing workers;
      appropriately isolating patients; record-keeping; and evaluation. Curricula in
      schools for health professionals should include material on ways to achieve good
      health for health care workers. Public health officials and regulators should pay
      more attention to this arena.

PMID- 7639869
TI  - Safety and health in the construction industry.
AB  - Workers in the building, renovation, and demolition of roads and commercial
      structures in the U.S. suffer a disproportionate share of occupational fatalities
      and lost-time injuries. Nearly all of the injuries and deaths are preventable.
      The fatality rate from work-related ailments, such as cancers and silicosis, is
      believed to be excessive, but is not generally computed. The safety and health
      problems are tied largely to the construction industry's organization and how the
      work is performed. Many hazardous exposures result from inadequacies in access to
      information, measurement technology, and personal protective equipment. Potential
      solutions are in labor-management site safety and health planning and management,
      education and training of workers and supervisors, new technologies, federal
      regulation, workers' compensation law, medical monitoring, and occupational
      health delivery. Public health opportunities involve health care delivery
      systems, improved preventive medicine, disability determination and
      rehabilitation programs, and research, beginning with the standardization of data
      to monitor these problems.

PMID- 7639870
TI  - Workers' compensation in the United States: high costs, low benefits.
AB  - Studies suggest that income replacement is low for many workers with serious
      occupational injuries and illnesses. This review discusses three areas that hold
      promise for raising benefits to workers while reducing workers' compensation
      costs to employers: improving safety, containing medical costs, and reducing
      litigation. In theory, workers' compensation increases the costs to employers of
      injuries and so provides incentives to improve safety. Yet, taken as a whole,
      research does not provide convincing evidence that workers' compensation reduces
      injury rates. Moreover, unlike safety and health regulation, workers'
      compensation focuses the attention of employers on individual workers. High costs
      may lead employers to discourage claims and litigate when claims are filed.
      Controlling medical costs can reduce workers' compensation costs. Most studies,
      however, have focused on costs and have not addressed the effectiveness of
      medical care or patient satisfaction. Research also has shown that workers'
      compensation systems can reduce the need for litigation. Without litigation,
      benefits can be delivered more quickly and at lower costs.

PMID- 7639871
TI  - Advances in public health communication.
AB  - There have been tremendous advances in recent years in the innovative use of
      communication to address public health problems. This article outlines the use of
      communication techniques and technologies to (positively) influence individuals,
      populations, and organizations for the purpose of promoting conditions conducive
      to human and environmental health. The approaches described include social
      marketing, risk communication, and behavioral decision theory, entertainment
      education, media advocacy, and interactive decision support systems. We also
      address criticism of these approaches among public health professionals because
      of perceived discrepancies in their inherent goals and objectives. In conclusion,
      we call for the rapid diffusion of state-of-the-art public health communication
      practices into public health service agencies and organizations.

PMID- 7639872
TI  - Bayesian statistical methods in public health and medicine.
AB  - This article reviews the Bayesian statistical approach to the design and analysis
      of research studies in the health sciences. The central idea of the Bayesian
      method is the use of study data to update the state of knowledge about a quantity
      of interest. In study design, the Bayesian approach explicitly incorporates
      expressions for the loss resulting from an incorrect decision at the end of the
      study. The Bayesian method also provides a flexible framework for the monitoring
      of sequential clinical trials. We present several examples of Bayesian methods in
      practice including a study of disease progression in AIDS, a comparison of two
      therapies in a clinical trial, and a case-control study investigating the link
      between dietary factors and breast cancer.

PMID- 7639873
TI  - Public health informatics: how information-age technology can strengthen public
      health.
AB  - The combination of the burgeoning interest in health, health care reform and the
      advent of the Information Age, represents a challenge and an opportunity for
      public health. If public health's effectiveness and profile are to grow,
      practitioners and researchers will need reliable, timely information with which
      to make information-driven decisions, better ways to communicate, and improved
      tools to analyze and present new knowledge. "Public Health Informatics" (PHI) is
      the science of applying Information-Age technology to serve the specialized needs
      of public health. In this paper we define Public Health Informatics, outline
      specific benefits that may accrue from its widespread application, and discuss
      why and how an academic discipline of public health informatics should be
      developed. Finally, we make specific recommendations for actions that government
      and academia can take to assure that public health professionals have the
      systems, tools, and training to use PHI to advance the mission of public health.

PMID- 7639874
TI  - International aspects of the AIDS/HIV epidemic.
AB  - This review provides the reader with pertinent information on the epidemiology,
      prevention, and new technologies of the ongoing HIV pandemic. These aspects are
      key to international policy discussions surrounding the public health response to
      the international spread of HIV. Our understanding of the impact of AIDS on other
      diseases is evolving, as is our insight into the demographic and economic effects
      of the epidemic on the global community. Observations on the success of certain
      prevention strategies allow rational allocation of resources in newly affected
      epidemic areas. Information on the origin and nature of HIV transmission
      exemplifies the phenomenon of global emerging infections. As world populations
      are brought closer together through transportation, communication, trade, and
      commerce, insight into emerging infections of epidemic potential becomes
      increasingly important to the practitioner of public health. Although important,
      legal and social aspects of the epidemic will not be emphasized here. The
      epidemics of HIV/AIDS in the United States and Europe are not reviewed here. The
      global pandemic has recently been described in an overview in this publication to
      which the reader is also referred.

PMID- 7639875
TI  - Tuberculosis, public health, and civil liberties.
AB  - The resurgence of tuberculosis confronts policy-makers with difficult legal and
      ethical questions about the proper use of state power and resources to protect
      public health. This chapter examines the implications of expanded use of invasive
      or coercive measures-including directly observed therapy, involuntary detention
      of noncompliant patients, and forced administration of medications--designed to
      reduce the risk of tuberculosis transmission and to ensure that those with TB are
      fully treated. These measures focus attention on the limitations of government
      power and obligation and on the delicate balance between the demands of civil
      liberty and the demands of public health.

PMID- 7639876
TI  - The status of health assessment 1994.
AB  - General health status and a broader concept of quality of life are discussed and
      methods of widely used surveys are reviewed. A consensus regarding the inclusion
      of measures of physical, mental, social, and role functioning and general health
      perceptions is noted for comprehensive assessments of health. A schematic of
      relationships among condition-specific and generic measures is presented along
      with results expected for objective and subjective measures of physical and
      mental dimensions of health. Suggestions are offered for the labeling of disease
      specific and generic measures and ways to avoid confounding of content.
      Applications of health surveys in general population monitoring, health policy
      evaluation, clinical trials of alternative treatments, monitoring and improving
      of health care outcomes, and in everyday clinical practice are exemplified and
      discussed. A unified measurement strategy is proposed and arguments in favor of
      standardizing the content of health surveys across applications are offered.

PMID- 7639877
TI  - Incidence, risk factors and prevention strategies for work-related assault
      injuries: a review of what is known, what needs to be known, and countermeasures
      for intervention.
AB  - This review organizes available data to address current epidemiological
      understanding of injuries from workplace assaults. We describe the incidence and
      general populations at risk for fatal and nonfatal work-related injury, and
      assess available information on risk factors and countermeasures considered
      important in reducing injury occurrence. Overall rates of occurrence of work
      related homicides and nonfatal injuries are estimated, and those factors that
      appear to be consistent across studies are explored. Much of what is known about
      occupations at high risk for assaults and injuries comes from a small number of
      documents and special studies within subsets of workplaces. Unfortunately, the
      potency of specific countermeasures for prevention of violence-related injury in
      work settings continues to be largely unknown. Numerous fundamental questions
      remain to be answered: Critical is a full assessment of risk, identification of
      situations and circumstances amenable to intervention, and evaluations to
      demonstrate effectiveness.

PMID- 7639879
TI  - Risk adjusting community rated health plan premiums: a survey of risk assessment
      literature and policy applications.
AB  - This paper surveys recent health care reform debates and empirical evidence
      regarding the potential role for risk adjusters in addressing the problem of
      competitive risk segmentation under capitated financing. We discuss features of
      health plan markets affecting risk selection, methodological considerations in
      measuring it, and alternative approaches to financial correction for risk
      differentials. The appropriate approach to assessing risk differences between
      health plans depends upon the nature of market risk selection allowed under a
      given reform scenario. Because per capita costs depend on a health plan's
      population risk, efficiency, and quality of service, risk adjustment will most
      strongly promote efficiency in environments with commensurately strong incentives
      for quality care.

PMID- 7639878
TI  - Methodological challenges in injury epidemiology and injury prevention research.
AB  - In the past decade there has been increasing attention to the public health
      importance of injuries. Public health agencies seeking to reduce injuries need
      methods for counting injuries, calculating injury rates, identifying the causes
      of injuries, and measuring outcomes of interventions. All of these areas present
      problems for injury epidemiologists and injury prevention programs. This paper
      provides a framework for classifying these problems into five categories: (a)
      numerator problems; (b) denominator problems; (c) causation; (d) exposure
      measurement problems; and (e) multiplicity. For most problems, we identify proven
      or potential solutions, using examples from the literature of injury
      epidemiology.

PMID- 7639880
TI  - Exposure assessment error and its handling in nutritional epidemiology.
AB  - Exposure assessment is the weakest element in nutritional epidemiologic studies.
      In the absence of an adequate arsenal of biomarkers of intake in the United
      States, food frequency questionnaires are widely used to assess habitual
      frequency of consumption of foods. These tools need to be designed for the
      population under study, based on prior information on the eating behavior of the
      population. The questions to be addressed to insure appropriate application of
      these tools are presented. The influence of various sources and types of
      measurement error on various scientific hypotheses is addressed. In assessment of
      nutrient adequacy, information on intra- to interindividual variation of the
      nutrient or substance of interest is essential. Risk assessment requires
      examination of sources and extent of bias and differential and nondifferential
      measurement error within the study. The theory required for error correction is
      well developed, but rarely carried out because of lack of software and lack of
      information needed to calibrate the measures.

PMID- 7639881
TI  - Variations in resource utilization among medical specialties and systems of care.
AB  - As sweeping changes in the organization and delivery of health care are
      implemented, it is important to examine the relationship between various types of
      cost-containment efforts, health care costs, and quality of care. This article
      reviews the evidence that physician specialty training, the organization of
      physicians, and the method of physician payment are significant influences upon
      the utilization of health care services. Data from before the late 1980s raised
      the possibility that family practitioners employed fewer resources than general
      internists and that health maintenance organizations used fewer resources than
      solo practitioners. However, the studies from which these data were derived were
      marred by insufficient attention to patient mix, failure to account for
      interactions between specialty and system, and inadequate regard for the
      complexities of modern practice structures. More recent data from the Medical
      Outcomes Study (MOS) overcomes some but not all of these problems. In general, it
      can be safely concluded that primary care specialty training, group practice, and
      prepaid care are associated with less utilization. Nevertheless, much more
      research is needed to address remaining methodological problems and to obtain
      data that are generalizable to the wide array of modern practice settings.

PMID- 7639882
TI  - Nonfinancial barriers to care for children and youth.
AB  - Public health and medical care interventions have produced dramatic changes in
      the health of children in the United States. Emerging new morbidities such as
      behavioral and learning disorders, and child abuse and neglect, highlight the
      lack of an integrated system of health. Children's developmental vulnerability,
      dependency, and unique morbidities have been underemphasized in the organization
      and delivery of health care. The Andersen and Aday model of health care
      utilization is used to describe financial and nonfinancial barriers to care for
      children that include family characteristics and organizational characteristics
      of the health system. Case studies of immunization delivery, children with
      chronic illness, and mobile populations of children reveal the mismatch between
      the health care system and children's basic health needs. Integrated service
      models for high-risk populations of children represent an essential mechanism for
      coordinating the delivery of medical, developmental, educational, and social
      services needed by children and families. Universal, coordinated public health
      and medical services of adequate scope and quality should be assured for children
      through market and health system reform.

PMID- 7639883
TI  - Medicaid managed care: contribution to issues of health reform.
AB  - This chapter examines the emergence of managed care in Medicaid from an
      alternative to the mainstream delivery system for many beneficiaries. It offers a
      definition that encompasses the broad spectrum of program manifestations, and
      presents a brief historical perspective on the major eras of managed care in
      Medicaid. The major program prototypes are described and their contribution to
      enrollment growth is discussed. Research evidence is examined to address both
      operational issues and program impacts. Finally, we conclude with an appraisal of
      contemporary issues of importance and speculation on the next generation of
      Medicaid managed care programs with an eye to how federal and state health care
      reform proposals will shape this future.

PMID- 7639884
TI  - Ecologic studies in epidemiology: concepts, principles, and methods.
AB  - An ecologic study focuses on the comparison of groups, rather than individuals;
      thus, individual-level data are missing on the joint distribution of variables
      within groups. Variables in an ecologic analysis may be aggregate measures,
      environmental measures, or global measures. The purpose of an ecologic analysis
      may be to make biologic inferences about effects on individual risks or to make
      ecologic inferences about effects on group rates. Ecologic study designs may be
      classified on two dimensions: (a) whether the primary group is measured
      (exploratory vs analytic study); and (b) whether subjects are grouped by place
      (multiple-group study), by time (time-trend study), or by place and time (mixed
      study). Despite several practical advantages of ecologic studies, there are many
      methodologic problems that severely limit causal inference, including ecologic
      and cross-level bias, problems of confounder control, within-group
      misclassification, lack of adequate data, temporal ambiguity, collinearity, and
      migration across groups.

PMID- 7639885
TI  - Biomarkers and mechanistic approaches in environmental epidemiology.
AB  - Environmental epidemiological research involves the identification of
      relationships between previous exposures to putative causative agents and
      subsequent biological effects with study populations. Such relationships are
      often hard to fully characterize because of difficulties in accurately
      quantifying exposure, dose, and effect. Biomarkers are indicators, residing in
      biological systems or samples, of exposure, dose, effect, or susceptibility.
      Biomarkers of exposure indicate the presence of previous exposure to an
      environmental agent; a biomarker of dose bears a quantitative relationship to
      previous exposure or dose; these include exogenous substances, interactive
      products, or interactions that change the status of the target molecule.
      Biomarkers of effect indicate the presence and magnitude of a biological response
      to exposure to an environmental agent; these include endogenous components, or
      measures of the functional capacity or state of the system. Biomarkers of
      susceptibility indicate an elevated sensitivity to the effects of an
      environmental agent; these include the presence or absence of an endogenous
      component, or abnormal functional responses to an administered challenge. The
      development of molecular biomarkers for environmental agents is based upon
      specific knowledge of metabolism, interactive product formation, and general
      mechanisms of action. The validation of any biomarker-effect link requires
      parallel experimental animal and human epidemiological studies.

PMID- 7639886
TI  - The future of the Nordic Council for Arctic Medical Research.

PMID- 7639887
TI  - Growth patterns of Canadian Inuit children. A longitudinal study.
AB  - A longitudinal study has examined the growth of height, sitting height, body mass
      and triceps skinfolds in a sample of Inuit (281 boys and 266 girls) attending the
      Igloolik school between the years 1981 and 1989. Heights were around the 10th
      percentile of U.S. norms for 1970. A peak height velocity of 9.2 +/- 2.3 cm/year
      was reached by girls at 11.3 +/- 0.7 years, and in boys the peak rate of 8.6 +/-
      3.7 cm/year was seen at 13.5 +/- 0.8 years. Sitting heights were also low
      relative to urban norms. Body mass approached the 50th percentile of U.S. norms,
      giving a large mass for height ratio at all ages. Triceps thicknesses for the
      girls were around the 10th percentile of urban norms, and in the boys began
      around the 25th percentile, but dropped steadily to the 5-10th percentile. No
      significant differences of growth patterns were seen between cohorts formed from
      students born in the years 1970/72, 1973/74 and 1975/76. However, comparison with
      earlier cross-sectional surveys in the same community showed a secular trend to
      greater stature and greater skinfold readings as the community had become
      acculturated to such features of modern living as mechanized transport and
      television. There were no systematic differences of growth rates between the
      summer and the winter seasons, and nutrition was good throughout. We thus
      conclude that the short stature has an inherited basis. Attention is drawn to the
      problem of interpreting curves of growth and weight for height in populations
      with an unusual body build.

PMID- 7639888
TI  - Validity of urine-blood hydrational measures to assess total body water changes
      during mountaineering in the sub-Arctic.
AB  - Mountaineering involves high altitude and cold exposure which are each associated
      with significant levels of dehydration (via altitude-cold diuresis, high energy
      expenditures, and poor access to water). The purpose of this study was to
      identify and validate urine and blood indices of dehydration as compared to
      changes in total body water (which served as the reference standard). Male
      subjects (n = 10) were studied during a 14 day mountaineering expedition in the
      sub-Arctic during which they climbed to an altitude of 5245 +/- 229 m (mean +/-
      SE). Daily activity consisted of approximately 10-15 hours skiing, hiking, and
      performing mountaineering tasks with heavy loads (> 30 kg). Various measurements
      were made immediately before ascending (Pre) and after descending (Post) the
      mountain: body weight (Bw) and composition (%Fat), urine specific gravity (USG),
      urine protein (UP), plasma electrolytes (K+, Cl-, Na+), plasma proteins (PP),
      plasma and urinary osmolality (UOsm), hematocrit (Hct), hemoglobin (Hb), blood
      urea nitrogen (BUN), plasma aldosterone, and total body water (TBW determined via
      deuterium oxide). Post the expedition significant (p < 0.05) decreases were
      observed in Bw, and %Fat, while significant increases were found in Na+, K+, USG,
      UOsm and UP. TBW was slightly reduced, however, changes were non-significant (Pre
      = 52.9 +/- 1.2 L vs. Post = 52.6 +/- 1.3 L). USG is often used to monitor
      hydration status in field settings; however, no significant correlations were
      found between changes in TBW and USG, nor between changes in TBW and other
      typical urinary indicators of dehydration.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7639889
TI  - Mercury, dental amalgam fillings and intellectual abilities in Inuit school
      children in Greenland.
AB  - The hair mercury concentration of 125 Greenland pupils aged 12 to 17 was recorded
      and compared with the pupils' marks in selected school subjects. Mercury values
      ranged from 0.2 to 15.9 microgram per gram (micrograms/g) and 20% of the pupils
      had more than 6 micrograms/g. There was no correlation between a high mercury
      concentration score and poor results in school. Correlation of the number of
      dental amalgam fillings with mercury concentration showed a weak trend but no
      significant relation. Eating habits were significantly correlated with mercury
      concentration. Girls had a significantly higher number of amalgam fillings than
      boys, and had a significantly higher mercury concentration. Modern Inuit and the
      mummified Qilaqitsoq Inuit from the 15th century had largely identical levels of
      mercury in the hair irrespective of today's higher exposure to global
      environmental contamination. This is believed to result from a change in eating
      habits away from the traditional Greenland food towards a more continental diet.

PMID- 7639890
TI  - Thyroid hormone responses to military winter exercises in the Arctic region.
AB  - The effects of military field exercises in the arctic on thyroid hormone
      concentrations were examined in Norwegian soldiers (n = 35). Originally the
      soldiers were divided into 4 groups having low (2 h) or high (6 h) levels of
      daily sleep, and low or high physical work requirements during the field
      exercises. The operations were three days of stimulated combat scenarios during
      winter. Day 1 consisted of 30 h without sleep. Sleep was then provided at
      approximately 18-22 h intervals thereafter. Blood samples were taken immediately
      prior to the exercises (BASELINE), during the exercises at 24 h, 48 h, and 72 h,
      and at 24 h and 48 h of recovery from the exercises (REC1, and REC2). Hormonal
      analysis consisted of total (T) thyroxine (TT4), free (f) T4, total
      triidothyronine (TT3), fT3, and thyroid stimulating hormone (TSH). No significant
      group interactions were observed therefore groups were pooled. However, main
      effects over time (i.e., days) were observed for all hormones (p < 0.001). TSH
      declined throughout the exercises, as did fT3. TT4, fT4, and TT3 increased in the
      first 24 to 48 h of the exercises, then progressively declined thought REC1. By
      REC2, TT4, fT4, and TSH showed trends towards returning to BASELINE levels,
      although recovery was not complete. The findings from this study demonstrates
      that thyroid hormone concentrations become reduced with as little as 72 h of
      military field operations in an arctic winter environment. However, short-term
      sleep deprivation and differing levels of physical work seem to have no major
      impact on the magnitude of the hormonal changes.

PMID- 7639891
TI  - Human endocrine responses to the cold.

PMID- 7639892
TI  - Proceedings from the symposium on Family Health in Circumpolar Regions.
      Ilulissat, Greenland, April 18-22, 1994.

PMID- 7639893
TI  - Mental health promotion among American Indian children.
AB  - Programs designed to promote mental health of the children of the Navajo Indian
      Tribe bear priority status. 1. Among these programs are the Brazelton Neonatal
      Behavioral Assessment Scale, a psychological and physical assessment of the
      neonate. It is designed to enhance bonding as well as identify and treat neonates
      affected by intrauterine alcohol or other drug use of the mother during
      pregnancy. 2. Description of a Fetal Alcohol Syndrome project enabling over 90%
      of those enrolled to refrain from using alcohol during their pregnancies. Many
      alcohol counsellors are employed for the entire Reservation. 3. Outreach to day
      and boarding school aids in many ways, including suicide prevention. 4. Use of
      knowledge and respect for patients' culture as vital to the treatment process. 5.
      "Back to Native values" program, involving using not only families but clans in
      the treatment of problems of children, including sexual or physical abuse and
      violence. This provides another treatment dimension, while enhancing the self
      esteem of the Native people. 6. The social work, substance abuse and mental
      health programs have been combined into one department named "Place of Healing",
      a Navajo term.

PMID- 7639894
TI  - Preventive health programs among Sami adolescents in a Sami community.
AB  - The town of Karasjok had during the eighties one of the highest prevalence of
      suicide among young men with a cluster of deaths in 1987 and 1988. This situation
      highlighted the life situation of the Sami adolescents in this area and a special
      suicide prevention program was established. Health and social workers from the
      primary health care in the town, the psychiatric outpatient clinics, the school,
      the church among others, worked together in an emergency interventional service
      for suicidal patients and postventional for the survival relatives and friends.
      In addition the preventive aspects of health services for the youth were focused.
      Firmer health services in the primary care in the town were reorganized to
      recognize and treat children and adolescents with special problems and needs. The
      school nurses got a central role in the schools available for children and
      teachers both in treatment, counselling and teaching. A special health service
      for youth, "the Youth office," was established one evening in the week staffed
      with a doctor and a nurse. All consultations are free and to make a data is not
      necessary. Everyone who wants a consultation gets it on the same evening. The
      Youth office runs evenings with films and discussions on special topics which the
      youth themselves want to learn more about as contraceptives, AIDS, abortion,
      friendship, the relationship between a boy and a girl and so on. This offer is
      very popular, but mostly among girls. The staff also organizes courses for other
      professionals in cooperation with the youth.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7639895
TI  - Child survival in Greenland.
AB  - The high infant and child mortality in Greenland covers significant differences
      among geographic regions. In the capital, Nuuk, 14 of 1000 live born children die
      before their first birthday, in the remote communities of northern and eastern
      Greenland the figure is 45. An independently higher mortality risk has also been
      demonstrated in children of mothers with alcohol problems, frequent admissions to
      hospital, and various other characteristics. A substantial proportion of infant
      and child deaths are potentially avoidable, either through improved health
      services or through action at community level. Based on the results of a research
      project certain concrete actions have been proposed and adopted by the health
      authorities.

PMID- 7639896
TI  - Improving child survival in Greenland.
AB  - Infant and child mortality have been shown to be high in Greenland compared with
      northern European countries. Mortality is highest in the socioeconomically less
      developed areas, and the medical reasons are particularly perinatal conditions,
      infectious diseases, and injuries. However, possibilities for making correct
      diagnosis are poor, and so are possibilities for an effective, systematic
      preventive effort. Recent studies indicate that stillbirths and child deaths
      below the age of 15 can be divided into avoidable and unavoidable deaths, and
      that avoidable deaths under local circumstances count for 16%. Therefore, it has
      been decided to systematically try to improve child survival primarily based on
      the following program: 1. Establishing a Pediatric Death Review Committee. 2.
      Education of health care workers, and 3. Improvement of the equipment status. The
      main goals of the program are to reduce infant mortality by 40% within a 4 year
      period, to reduce the number of child deaths in the age group 1-14 by 20%, and to
      reduce regional differences in child mortality in Greenland by 50%.

PMID- 7639897
TI  - Investigation and management of cervical intraepithelial neoplasia in Canadian
      Inuit: enhancing access to care.
AB  - Cervical intraepithelial neoplasia (CIN) is a major cause of morbidity among
      Circumpolar women. Cervical cancer comprised 15% of all cancers in Canadian Inuit
      women from 1969-1988. The age standardized incidence for invasive cervical cancer
      in Canadian Inuit women is 3.1 times the rate in the general Canadian population.
      Management of CIN in women of remote Arctic regions has traditionally required
      multiple visits to specialized medical centres for diagnosis, therapy and follow
      up. Such centralized care requires separation of women from their families,
      resulting in significant medical, emotional and economic costs for the patient,
      her family and community. In the Canadian Central Arctic, a program for the
      diagnosis and therapy of CIN has been established using colposcopy with loop
      electrosurgery, performed by a trained local family practitioner and visiting
      gynecologist. Early program evaluation has indicated reduction in medical
      expenditures due to travel costs, minimal procedure-related morbidity and
      discomfort, and improved patient satisfaction associated with reduced separation
      from family and community. It is hoped that the program design, which harnesses
      technology in order to provide improved care closer to home, will be applicable
      to other Circumpolar regions.

PMID- 7639898
TI  - Legal abortion in Greenland. Report from a workshop.

PMID- 7639899
TI  - Early mother-child relationship. The Copenhagen model of early preventive
      intervention towards mother-infant relationship disturbances.
AB  - The development of interactive patterns in the first year of life has been
      studied in healthy mother-infant pairs and in infants whose mothers have
      psychiatric or psychosocial problems, interfering with their relation to the
      child. During the first 3 months a relationship develops in healthy mother-infant
      pairs characterized by an intimate interchange of signals and responses between
      mother and child. The baby develops a basic pattern of social relating. During
      the next months the baby begins to expect the mother to fulfil it's wishes and
      still the mother adapts to and supports the baby's expanding capacities and
      needs. A beginning sense of self and not-self develops. At 10-12 months the
      infant is able to move around trying to examine everything within range. At this
      age the infant senses that there exist other wills and minds than it's own. The
      child looks at the mother and reads her expressions for "yes", "no", and "maybe".
      The mother can stop or encourage her child by verbal and body signals. At 12-18
      months the child has developed a secure attachment apt to protect the child
      against later adversities. The development during the first year of life may be
      seriously disturbed if the mother cannot adapt to and support the baby's signals
      and needs. Relationship disturbances in the first year of life may be related to
      maternal or infant problems: Low birth weight babies, irritable babies with low
      stimulus tolerance and babies with withdrawal reactions following maternal
      alcoholism or drug abuse during pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7639900
TI  - Vicissitudes of attachment: nurturance and dependence in Canadian Inuit family
      relationships, old and new.
AB  - This paper describes complex and counterbalancing motivations underlying
      attachment, which governed social life in traditional Inuit camps and continue to
      influence Inuit behaviour in modern settlements. These motivational patterns are
      capable of maintaining a strong sense of personal worth and connectedness with
      other people; but they can malfunction in difficult circumstances. The differing
      vicissitudes of nurturance and dependence in camps and in settlements are
      described, with focus on the development of a vicious circle, which can afflict
      the self-esteem of Inuit who live under modern conditions.

PMID- 7639901
TI  - Skolt Saami socialization with special reference to the traditional eco-culture
      and on-going changes.
AB  - The paper presents selected findings on socialization from a long-term
      psychological project conducted among the Skolt Saami living in the north of
      Finland. The data are based on participant observation, interviews (Schaefer's
      scale: school-aged children's perceptions of their parents, N = 64; and Block's Q
      sorting method for their parents; interviews with almost all the adult Skolts; N
      approximately 500;) (1). The basic studies of the research project was carried
      out in 1967-74, and changes in socialization have been followed up in several
      phases later on. Comparisons are drawn with the majority culture of Northern
      Finland (61 children and their parents). Changes in ecology, economics and
      accultration have modified the roles of adult Skolts, affecting the men and women
      differently, and having repercussions for their paternal and maternal
      aspirations, power and influence. The changes were less confusing for the Skolt
      women than for the men whose role underwent a radical shift. Under these
      circumstances the wife was the head of the family, her responsibilities, power
      and influence increased. The developmental process in socialization has been
      characterized by a search for balance between the traditional life style and
      attitudes and the challenges and conflicts that arise from the culture and
      education of the majority.

PMID- 7639902
TI  - Changing roles in Sami families--a case illustration.
AB  - During the last 20-30 years the Sami society has undergone an accelerating
      process of change. A planned national policy to integrate the Samis into the
      Norwegian nation state making them "equal members of our nation state", has
      resulted in dramatic changes in the standard of living, the educational patterns,
      and the structure of settlement, occupation and industry. This process of change
      has dramatically changed the life situation of the Sami people. This paper will
      examine how these external macroprocesses have changed the role and
      responsibilities of the family and its members. Special consideration will be
      given to gender and generational aspects.

PMID- 7639904
TI  - Families in distress, the development of children growing up with alcohol and
      violence.
AB  - Growing up in a family with alcohol problems and violence means a greater risk of
      abuse and neglect depending on: who is the alcoholic, how violent is the
      violence, social conditions, social status, relations outside the family and
      individual factors in the child (the resilient child). The psychological
      environment in which the children are raised is characterized by: having
      experienced one or both parents losing contact with reality because of being
      drunk, fear of losing one or both parents because of death, fear of not being
      loved and fear of being stigmatised if it is known, that one or both parents are
      alcoholics and/or violent. Results show that the more passive forms of neglect
      are the most common and that children develop strategies for survival. The
      presentations will be based on four Danish research projects 1988, 1990, 1992 and
      1994 by the author.

PMID- 7639903
TI  - Male sexuality and sexual offences.
AB  - Men in contemporary western societies differ from women regarding several sexual
      expressions. For example, men show a more stationary, linear sexual desire, more
      often separate sex-life from love-life, engage in heterosexual or homosexual one
      night-stands and more often buy sex from a prostitute. Some sexual deviations
      manifest themselves only in males. Most sexual offences are committed by mean.
      Sexual assaults are, of course, unacceptable. But sexual offences are often a
      token of powerlessness when failing in relation to oneself and/or other people.
      Thus not only victims of sexual assaults, but also the perpetrators need help in
      order to prevent further sexual assaults. In the paper some experiences with
      therapy of sexual offenders in Denmark and Germany are discussed.

PMID- 7639905
TI  - Mental disorders and conditions of life in childhood in Greenlanders.
AB  - A cohort of Greenlandic psychiatric patients, domiciled in Greenland and admitted
      for the first time to a psychiatric institution in 1980-84, has been analyzed and
      followed until 1991. In this part of the study their conditions in childhood were
      analyzed in relation to diagnoses. Failing care, disharmony and possible violence
      in the early home were associated with great risk of later personality disorders,
      whereas they were not associated with a neurotic development. No direct
      association was found with the structure of the early home, whether or not
      spending the whole childhood with both or one of the biological parents. It was
      the quality of the home(s) that mattered. For other diagnoses there was no clear
      association between conditions in childhood and occurrence of the diagnosis. But
      there was an astonishingly high prevalence of poor conditions in childhood in the
      total study population, especially among those younger than 35 years at first
      admission.

PMID- 7639906
TI  - A one year Greenlandic study of temporary and permanent placement of children and
      adolescents outside their homes.

PMID- 7639907
TI  - A keynote on family health.

PMID- 7639908
TI  - Experiences from a consultative journey to Greenland presented by a child
      psychiatrist and a psychologist.
AB  - This consultative journey to Greenland was the first to be made recently by a
      child psychiatrist and should be given serious considerations. The material is
      selected because of the arbitrariness in the referrals as child psychiatry is not
      (yet) continuously available on Greenland. When this is taken into consideration
      there seems to be an overrepresentation of emotional disorders, pathological and
      prolonged reactions of grief and of crisis and of conduct disorders. In
      connection with this we have put forward some hypotheses that the difficulties
      perhaps are caused by more specific conditions in the Greenlandic society, for
      instance, the Greenlandic "way of communication" and changes of upbringing of
      children, particularly boys.

PMID- 7639909
TI  - The population survey as a tool for assessing family health in the Keewatin
      region, NWT, Canada.
AB  - The population survey is an important tool in community health assessment,
      including the physical and psychological aspects of family health. It provides
      data on health status and health determinants not available from vital statistics
      and health service utilization. The Keewatin Health Assessment Study (KHAS),
      which was designed in collaboration with the Keewatin Regional Health Board
      (KRHB), surveyed a representative sample of the predominantly Inuit population in
      8 communities in the central Canadian Arctic. The entire survey included 874
      individuals in all age groups, of whom 440 were children and adolescents under 18
      years of age, and consisted of questionnaires, clinical examination and
      laboratory tests. Of the large number of variables on which data were collected,
      some were of particular relevance to the health of children and the well-being of
      the family, including: (1) Child growth and development; (2) Nutrition and diet;
      (3) Social pathologies: suicide attempts and sexual abuse; (4) Oral health; and
      (5) Audiologic health. In addition to providing cross-sectional data, survey
      participants constitute a cohort which, if followed up longitudinally, can be
      used to determine the incidence of specific conditions and identify risk factors
      which promote or prevent their occurrence. An example of such a cohort study is
      one on acute respiratory infection. Surveys serve many functions--providing data
      for planning and evaluation, promoting community awareness of health issues, and
      addressing basic research questions. The KHAS is one of several surveys launched
      over the past several years which jointly will begin to provide a circumpolar
      perspective on the health of Inuit people.

PMID- 7639910
TI  - The Icelandic child mental health study.
AB  - The purpose of this study was to test the applicability of a standardized
      procedure for assessing Icelandic children's behavior/emotional problems and
      competencies, and to identify differences related to demographic variables. This
      study focuses upon the method of using the Child Behavior Checklist by Achenbach
      to estimate the self-reported prevalence by parents and adolescents of emotional
      and behavior problems in children from 2-16 years of age and self-reported
      prevalence of adolescents from 11-18 years, selected at random from the general
      population, both in urban and rural areas. The information was obtained by
      mailing lists with a letter to parents of children 2-10 years of age. The lists
      for adolescents 11-18 years of age were distributed by teachers in school. Those
      adolescents who were not in school received the lists by mail at their homes. The
      Child Behavior Checklists used for analyses were completed by 109 parents of 2-3
      year old children; 943 parents of 4-16 year old children, and 546 non-referred
      adolescents from the general population. The rate of response was lowest for the
      youngest age group (47%), but increasing to 62% with increasing age of the child.
      The response rate among the adolescents answering the Youth Self Report was 64%.
      Comparisons are presented with the Child Behavior Checklist for this study with
      Dutch, American, French, Canadian, German and Chilean samples and show striking
      similarities in four of these countries in behavior/emotional problems reported.
      The present study prevalence data behavior/emotional problems in Icelandic
      children from the general population from 4-16 year olds for 943 children is 17.5
      (boys 19.1; girls 15.).

PMID- 7639911
TI  - Health interview survey in Greenland.
AB  - The Greenland Health Interview Survey was initiated in 1991 by the Greenlandic
      health authorities in order to generate a comprehensive and epidemiologically
      sound basis for health planning and prevention. Trained interviewers have
      collected information from June 1993 until now but results are not available yet.
      In a culturally sensitive frame of reference information is gathered on self
      perceived health, use of health services, life style and living conditions. The
      interviewers are indigenous lay persons and the main survey neither includes
      clinical examinations nor collection of blood specimens. The scope of the survey
      is broad and several topics are relevant for family health. The main
      questionnaire covers persons 18 years old and over.

PMID- 7639912
TI  - Drug prescription to children living in the Arctic. An investigation from Nuuk,
      Greenland.
AB  - The prescription pattern to children living in an arctic environment (Nuuk,
      Greenland) is similar to the pattern seen in other countries e.g. Sweden, Norway
      or the US, but the prescription rate of both anti-infectives and the total number
      of drugs is 2-3 times larger. This may reflect differences both in socioeconomic
      factors, in disease patterns and in sickness rate in children living in the
      Arctic. Inuit children are known to have a disease pattern that partly differs
      from the one seen elsewhere. Most drugs were prescribed to the youngest children
      who also received less phenoxymethylpenicillin and more other anti-infectives.
      2/3 of all drugs were prescribed during the winter (November to April). A small
      group of large scale consumers, 116 children or 7% of the children prescribed
      drugs, were prescribed anti-infective drugs 3 times or more and were prescribed
      more than 1/5 of all drugs to children in Nuuk in the year surveyed.

PMID- 7639913
TI  - Classifying urban crashes for countermeasure development.
AB  - Efforts to reduce urban crash rates have been hampered by a lack of information
      about motor vehicle crash types. The present study is based on a systematic
      sample of 4,526 police crash reports from four urban areas. The sample was
      weighted to give each area equal representation. Diagrams and narrative
      descriptions from each report were reviewed, and the most common crash types
      based on precrash driver/vehicle behavior, were identified. Fourteen crash types
      were defined, and five of these were found to account for 76% of all crash events
      and 83% of injury crashes. Although the rank order of the five types differed
      from city to city, they accounted for the vast majority (69%-81%) of the crashes
      in each. Potential countermeasures are discussed based on the predominant crash
      types identified in this study. For example, ran traffic control crashes, the
      most common types, might be reduced by changes in signal timing, providing all
      red signal intervals, increasing sign visibility, and increasing sight distances.

PMID- 7639914
TI  - Medical conditions, risk exposure, and truck drivers' accidents: an analysis with
      count data regression models.
AB  - Recent studies do not agree on the possible relationship between medical
      conditions and traffic safety; most of them do not control for exposure factors.
      This problem has become more pertinent for scientific studies because of
      litigation that showed that present regulations about access to driver permits
      might contravene human rights legislation. In our study, we estimate the effect
      of different medical conditions on truck drivers' distributions of accidents. Our
      data and our models permit simultaneous control for age; medical conditions;
      exposure factors measured by hours, kilometer, and qualitative factors; and other
      characteristics of truck drivers. Our results show that diabetic truck drivers of
      the permit class for straight trucks have more accidents than drivers in good
      health. No other studied medical condition has a significant effect on individual
      accident distributions. Many risk exposure variables are also significant. The
      effect of age is discussed in detail.

PMID- 7639915
TI  - Methods used in studies of drink-drive control efforts: a meta-analysis of the
      literature from 1960 to 1991.
AB  - We searched the drink-drive control literature over the past three decades,
      finding over six thousand documents. After detailed review of the abstracts and
      papers, 125 studies contained separate empirical evaluations of the effects of 12
      DWI control policies and enforcement efforts (administrative license suspension,
      illegal per se, implied consent, preliminary breath test, mandatory jail
      sentence, mandatory community service, mandatory license suspension, limits on
      plea bargaining, mandatory fines, selective enforcement patrols, regular police
      patrols, and sobriety checkpoints). The 125 studies contained 664 distinct
      analyses that formed the basis for meta-analysis. All of the DWI control efforts
      were associated with reductions in drink-driving and traffic crashes. The DWI
      control literature is limited by the preponderance of weak study designs and
      reports that often fail to include basic data required for meta-analysis. Because
      of the poor quality of much extant research, we were limited to simple gain
      scores or percent change estimates in the current study. Further research that
      does not include appropriate research designs and analytic methods will be of
      limited utility. We recommend that all future reports include effect estimates
      and standard error estimates, minimum data required for effective meta-analysis.

PMID- 7639916
TI  - Child pedestrian injury taxonomy based on visibility and action.
AB  - With data from multidisciplinary investigations of child pedestrian injuries in
      Chicago, a new and simpler four-category taxonomy is presented based on the
      process that led to the collision. Two dimensions are recognized: the visibility
      of the child and/or the vehicle immediately prior to the event and the rapidity
      of action, either movement or change in direction, of the victim or the vehicle.
      The taxonomy is neutral with respect to responsibility for the collision and
      accommodates the findings of other researchers. This classification scheme is
      tested empirically using objective data elements such as child gender and age and
      event location. It is further tested using the results of a multidisciplinary
      causal sequence reconstruction of each injury event, based on such factors as
      child's psychological character, traffic risks, driver behavior, visibility
      obstructions, whether the child negotiated part of the street before being
      struck, and child's activities immediately prior to the injury. The results show
      that events in the categories in this new taxonomy are distinctly different from
      each other, and that the structure is useful for identifying and organizing
      interventions.

PMID- 7639917
TI  - Alcohol, drugs, and impairment in fatal traffic accidents in British Columbia.
AB  - Blood samples and accident records of 41 female and 186 male fatally injured
      drivers were examined. Analyses suggested that drugs other than alcohol are
      causally related to fatal traffic accidents in British Columbia. Toxicologies
      showed: 37% alcohol only, 11% alcohol and drugs, and 9% drugs only. The most
      frequently found drugs were: 48% alcohol, 13% tetrahydrocannabinol or its
      metabolites (THC/THCCOOH), 4% cocaine, and 5% diazepam. In addition, alcohol-only
      impairment was missed by investigating police officers in many cases, impairment
      by alcohol and drugs was mistakenly identified as alcohol-only impairment, and
      drug-only impairment was misclassified as "driving without due care and
      attention".

PMID- 7639918
TI  - Road traffic offending and the introduction of speed cameras in England: the
      first self-report survey.
AB  - There is some evidence to suggest that the use of speed cameras to enforce speed
      limits can lead to a decrease in both speed violations and road accidents. The
      precise effects of such measures, however, are unclear. This paper describes an
      initial survey of driver attitudes and behaviour conducted following the
      experimental introduction of speed cameras in the United Kingdom. The survey was
      designed to determine, by means of drivers' self-reports, (a) to what extent
      drivers' choice of speed had changed due to the presence of speed cameras, and
      whether this change generalised to areas where cameras were absent; (b) the
      relationship between individual differences and the influence of the cameras; and
      (c) drivers' opinions of the use of cameras. Five hundred and twenty-four
      subjects completed a brief questionnaire. Overall, the results indicate that the
      presence of speed cameras is effective in reducing the speeds adopted by some
      drivers and that this effect, to some extent, generalises to areas without
      cameras. However, it is also apparent that those drivers who report adopting the
      most excessive speeds in general are the most likely to report driving more
      slowly in the presence of cameras, but no differently or faster in other areas.
      Overall, drivers in this sample expressed more positive than negative views about
      the presence of speed cameras. The implications of the results for the widespread
      introduction of speed cameras are discussed.

PMID- 7639919
TI  - Prediction of police officers' traffic accident involvement using behavioral
      observations.
AB  - The current study used scores on the Driver Performance Measurement (DPM) test
      and data gathered over four years on accident type and frequency from 47 police
      officers to provide evidence that cognitive-behavioral observations of driving
      patterns can lead to predictions of subsequent accident involvement. Results
      indicate that after controlling for age and experience, scores on the DPM test
      predicted involvement in preventable accidents but not unpreventable accidents.
      Implications for future research involving the observation of cognitive
      behavioral sequences are discussed.

PMID- 7639920
TI  - Relationship of helmet use and head injuries among motorcycle crash victims in El
      Paso County, Colorado, 1989-1990.
AB  - A case-control study was conducted in El Paso County, Colorado to estimate
      differences in risk of head injury among persons in motorcycle crashes who were
      or were not wearing helmets. There were 71 cases, motorcyclists with head
      injuries from crashes, and 417 controls, motorcyclists in crashes without head
      injuries. Motorcyclists not wearing helmets were 2.4 times as likely to sustain
      head injuries (95% confidence limits: 1.23, 4.70) than motorcyclists wearing
      helmets. This odds ratio was adjusted for age and crash characteristics, using
      logistic regression. Alcohol intoxication and severity of motorcycle damage were
      also associated with significantly elevated odds ratios related to sustaining a
      head injury.

PMID- 7639921
TI  - Effect of roadway geometrics and environmental factors on rural freeway accident
      frequencies.
AB  - This paper explores the frequency of occurrence of highway accidents on the basis
      of a multivariate analysis of roadway geometrics (e.g. horizontal and vertical
      alignments), weather, and other seasonal effects. Based on accident data
      collected in the field, a negative binomial model of overall accident frequencies
      is estimated along with models of the frequency of specific accident types.
      Interactions between weather and geometric variables are proposed as part of the
      model specifications. The results of the analysis uncover important determinants
      of accident frequency. By studying the relationship between weather and geometric
      elements, this paper offers insight into potential measures to counter the
      adverse effects of weather on highway sections with challenging geometrics.

PMID- 7639922
TI  - Characteristics of older road users and their effect on road safety.
AB  - This paper reports the results of several field surveys on the characteristics of
      older road users in Japan and of their traffic accident statistics. The results
      obtained are as follows: the reduced physical and mental functions with advancing
      age give improper driving characteristics to elderly drivers, but are not
      deterministic factors of quitting driving; the driving characteristics have some
      relation with traffic accidents; problematic drivers seem to emerge among elderly
      drivers; reduced functions are also related to the occurrence of accidents among
      elderly people in bicycle riding and walking. Further, a systematic and
      comprehensive approach is presented for traffic accident prevention among the
      elderly based upon these results.

PMID- 7639923
TI  - What is happening to the number of fatalities in road accidents? A model for
      forecasts and continuous monitoring of development up to the year 2000.
AB  - A model for successively forecasting and monitoring the development in the number
      of fatalities in traffic is presented. The model has been created through time
      series analysis covering the years 1977-1991. The model is simple, with the
      number of fatalities as the dependent variable and with time and traffic as the
      only predictors. The time factor describes the cumulative effect of changes such
      as better roads, vehicles, drivers, etc. The model is multiplicative and permits
      a nonproportional relationship with traffic volume. Taking into account the
      purely random fluctuations in the number of fatalities, the historical fit for
      the period 1977-1991 is very good. Also the forecasts for 1992 and 1993 have
      proved very accurate. The model will be revised as new annual data are received.
      At present, the model points to a favorable development in the reduction of the
      number of fatalities up to the year 2000, assuming a moderate increase in
      traffic.

PMID- 7639924
TI  - Risk factors and mechanisms of occurrence in motor vehicle-related spinal cord
      injuries: Utah.
AB  - The purpose of this paper is to describe the incidence, risk factors, and crash
      factors of motor-vehicle-related spinal cord injuries in Utah. The Utah
      Department of Health established a statewide registry of spinal cord injuries
      (SCIs) occurring in 1989-1991, analyzing data from hospital medical records and
      police reports. Forty-nine percent of all SCIs involved motor vehicles, including
      injuries arising from motor vehicle collisions with bicyclists and pedestrians.
      Adolescent and young adult males were at highest risk of injury. Among occupants
      of automobiles and trucks with SCI, 70% were involved in a vehicle rollover,
      while 39% were ejected from the vehicle. Only 25% reported using seatbelts. SCIs
      were much more likely to be associated with rollover compared with other types of
      motor vehicle-occupant injuries. These findings suggest areas in which SCI
      prevention programs and research should be focused.

PMID- 7639925
TI  - Age, sex, and blood alcohol concentration of killed and injured pedestrians.
AB  - The relationships between age, sex, and blood alcohol concentration were examined
      among all adult pedestrians fatally injured in South Australia from 1981 to 1992
      inclusive and among all adult pedestrians admitted to a Level 1 trauma center
      from August 1985 to July 1987. Among the 400 fatalities and 217 admissions,
      respectively, 68% and 60% were male, 35% and 21% were over 65 years of age, and
      38% and 29% had a BAC of .10 or above. Three distinct high-risk groups of adult
      pedestrians were identified: elderly sober pedestrians, young and middle-aged
      intoxicated males, and male and female teenagers. Temporal trends in numbers,
      rates, and extent of alcohol involvement of driver and pedestrian fatalities were
      examined for the years 1981 to 1992: the numbers and rates of driver and, in
      particular, pedestrian fatalities have decreased over the last decade, but the
      extent of alcohol involvement has declined significantly only among fatally
      injured drivers. Comparisons of the extent of alcohol involvement among fatally
      injured pedestrians, drivers, passengers, and motorcycle riders showed that
      alcohol involvement, particularly at the higher levels of blood alcohol
      concentration, was most prevalent among pedestrians.

PMID- 7639926
TI  - Are unintended hospital injury events avoidable?

PMID- 7639927
TI  - Antibody-directed enzyme prodrug therapy (ADEPT) with mustard prodrugs.
AB  - Antibody-directed enzyme prodrug therapy (ADEPT) is a two-step targeting
      procedure designed to improve the selectivity of anti-tumour agents. The approach
      is based on the activation of specially designed prodrugs by enzyme-antibody
      conjugates targeted to tumour-associated antigens. This review concerns ADEPT
      using nitrogen mustard prodrugs and carboxypeptidase G2 (CPG2) as the activating
      enzyme. The specific structural features required of the nitrogen mustard
      prodrugs, their design, syntheses, physicochemical properties, biological
      characteristics and activation to the corresponding drugs are reviewed. The ADEPT
      clinical trial with a nitrogen mustard prodrug is also discussed.

PMID- 7639928
TI  - Synthesis, DNA binding, and sequence specificity of DNA alkylation by some novel
      cyclic peptide-chlorambucil conjugates.
AB  - In an effort to investigate the potential of cyclic peptides as carriers for
      cytotoxic agents, we synthesized four cyclic peptide-chlorambucil conjugates:
      cyclo[Lys(CHB)-Lys(CHB)-Gaba-] (peptide Y), cyclo[Lys(CHB)-Gly-Lys(CHB)-Gaba-]
      (peptide A), cyclo[Lys(CHB)-beta-Ala-Lys(CHB)-Gaba-] (peptide B) and
      cyclo[Lys(CHB)-Gaba-Lys(CHB)-Gaba-] (peptide C). The cyclic peptides were
      synthesized by coupling protected amino acid residues in solution and the
      subsequent cyclization was performed by the pentafluorophenyl ester method as
      described previously (Sheh et al., 1990, 1993a,b). After deblocking the lysyl
      carbobenzyloxy protecting group (Z), the conjugation was achieved by reaction
      with the pentafluorophenyl ester of chlorambucil (CHB). These cyclic peptides
      differ from one another in ring size and are disubstituted with CHB via the
      epsilon-amino group of the lysyl residue. The various conjugates were designed to
      study the effect of ring size on the mode of DNA binding and alkylation. A DNA
      binding assay using lambda-DNA with ethidium bromide showed that whereas peptide
      Y and CHB have no observable binding affinity, the apparent binding constants for
      peptide A, peptide B and peptide C on lambda-DNA were determined to be 2.36 x
      10(5), 1.27 x 10(5) and 3.50 x 10(5), respectively. Thus, it is suggested that
      cyclic peptides bearing aliphatic side chains attached to a ring larger in size
      than 14 members would be more favourable as regards augmenting the binding
      affinity. DNase I footprinting showed that no footprinting patterns were observed
      for the 253-mer fragment and 117-mer fragment with peptide A, but two new bands
      corresponding to G69 and G80 were observed for the 117-mer fragment. DNA
      alkylation studies using a piperidine cleavage assay on the 117-mer DNA fragment
      showed that the sequence selectivity, judged by reaction intensity observed with
      peptide A, peptide B and peptide C, was similar to that seen with CHB alone. The
      selectivity of alkylation for both CHB and its peptide derivatives appears to be:
      3'-Pur-G-Pyr-5' > 3'-Pyr-G-Pyr-5' > 3'-Pyr-G-Pur-5' = 3'Pur-G-Pur-5'. However,
      there are apparent differences in the intensity of alkylation by peptides A, B, C
      and CHB at certain guanine residues.

PMID- 7639929
TI  - Design, synthesis, DNA sequence preferential alkylation and biological evaluation
      of N-mustard derivatives of distamycin and netropsin analogues.
AB  - The design and synthesis of certain oligopeptides structurally related to
      distamycin and netropsin, but bearing mixed heterocyclic moieties capable of
      recognizing alternative base sites and nitrogen mustard moieties capable of
      covalent binding to DNA, are described. The binding and thermally induced DNA
      cleavage, covalent interstrand cross-linking, DNA preferential alkylation and
      anticancer cytotoxicities of the new agents are described. In contrast to the
      mustard derivative derived directly from distamycin, the new agents give evidence
      of extensive DNA alkylation and interstrand cross-linking. In general, strong
      alkylation is observed at A residues for this class of agents, while the G
      residues that are alkylated appear to be more characteristic of individual
      compounds. Densitometric analysis of the frequency of bases adjacent to the
      alkylation sites (-3 to +3) revealed that the preferred bases are exclusively A/T
      with little preference shown for G bases and none for C sites. Further insight
      into the DNA alkylation processes afforded by the drugs was provided by an
      independent assay whereby heating the drug-DNA adduct with 10% aqueous piperidine
      only yielded strand breaks specifically at G-N7 sites in the major groove.

PMID- 7639930
TI  - Interference of new alkylphospholipid analogues with mitogenic signal
      transduction.
AB  - The interference of several new hexadecylphosphocholine analogues with mitogenic
      signal transduction was investigated in NIH3T3 fibroblasts by studying the
      effects of these agents on thrombin-induced inositol 1,4,5-trisphosphate
      (Ins(1,4,5)P3) formation and the subsequent Ca2+ release, on protein kinase C
      (PKC) in cell-free extracts, on the PKC-mediated activation of the Na+/H+
      antiporter and on c-fos induction. The compounds investigated include
      hexadecylphosphocholine (HePC), octadecyl-[2-(N-methyl-piperidinio)-ethyl]
      phosphate (D20133), octadecyl-(N,N-dimethyl-piperidinio-4-yl)-phosphate (D21266);
      octadecyl-[2-(trimethyl-arsonio)-ethyl]-phosphate (D21805) and hexadecylphospho-L
      serine (HePS). The data indicate that (i) all compounds inhibit the thrombin
      induced progression of growth-arrested NIH3T3 cells into S phase with similar
      IC50 values; (ii) the common denominator of all compounds is a reduction of
      Ins(1,4,5)P3 formation, resulting in an attenuation of Ca2+ release; (iii) the
      direct interaction with PKC does not significantly contribute to the antitumor
      activity of these agents; (iv) the new HePC congeners D21266, D21133 and D21805
      affect the same targets as HePC, i.e. PKC and phosphatidylinositol 4,5
      bisphosphate-specific phospholipase C (PLC). The lower toxicities of these
      compounds cannot be explained by a less pronounced inhibition of PKC or PLC,
      respectively.

PMID- 7639931
TI  - Abortive transcription of the T7 promoter induced by elsamicin A.
AB  - The capacity of two intercalating drugs, actinomycin D and elsamicin A, to act as
      obstacles to transcript elongation by T7 RNA polymerase was analysed using a
      transcription assay in vitro. Whereas actinomycin D only delayed the production
      of full-length ('run-off') transcripts from the T7 promoter, elsamicin A arrested
      the transcription after a short transcript was made, and full-length transcripts
      were not obtained. The halt of transcription at the drug binding sites close to
      the promoter causes transcript arrest and results in the formation of a stable
      RNA hairpin. Actinomycin D appears to be able to detach from the template,
      allowing the phage polymerase to read through the pause site. In this way, full
      length transcripts were obtained in a time-dependent way. With elsamicin A, a
      blockage of the transcription was observed which could be followed by the release
      of the phage RNA polymerase. The abortive transcription induced by elsamicin A
      might be explained considering that this DNA-binding drug drastically reduces the
      elongation rate and indirectly interferes with the polymerase during
      transcription, thus favouring its loose association with the nascent RNA and the
      inability of the enzyme to translocate along the DNA template. A direct
      interaction of the drug with the polymerase cannot be ruled out as an alternative
      explanation for the abortive transcription induced by elsamicin A.

PMID- 7639932
TI  - Serodiagnosis of leishmaniasis.
AB  - Leishmaniasis is a spectrum of diseases ranging in severity from cutaneous (CL),
      post-kala-azar dermal (PKDL), and diffuse cutaneous (DCL) to mucocutaneous (MCL)
      and visceral (VL) infections that are endemic in 86 tropical and subtropical
      countries around the world, accounting for 75,000 deaths per year. Different
      forms of leishmaniases are generally caused by different distinct species of
      Leishmania having a digenetic life cycle alternating between an aflagellated
      amastigote form replicative within the macrophages of the host and a flagellated
      promastigote form that multiplies within the gut of the sandfly. VL, MCL, PKDL,
      DCL, and CL forms of the disease can be arranged on a priority basis in
      accordance with the humoral immune responses of host. Generally, the cell
      mediated immunity, particularly the delayed-type hypersensitivity to leishmanial
      antigens, is associated with CL, MCL, PKDL, and cured VL cases. The serodiagnosis
      of leishmaniasis appears to be an alternative to parasite detection in biopsy
      samples either by the staining of amastigotes or by culturing the amastigotes,
      which transform to a promastigote form and replicate. A battery of immunological
      procedures have been developed or adapted to demonstrate either humoral or cell
      mediated immune responses against Leishmania for diagnosis and epidemiological
      survey. The sensitivity and specificity of such diagnostic methods depend on the
      type, source, and purity of antigen employed, as some of the leishmanial antigens
      have common cross-reactive epitopes shared with other microorganisms,
      particularly Trypanosoma, Mycobacteria, Plasmodia, and Schistosoma.
      Serodiagnostic techniques for the detection of antileishmanial antibodies have
      been employed with about 72 to 100, 23 to 90, 83, and 33 to 100% success in VL,
      CL, MCL, and PKDL patients, respectively. The Leishmanin skin test (LST) is
      useful to detect MCL and CL, with about 100 and 84% success, respectively. In
      PKDL, the gradual fall of antileishmanial antibody titer to some extent and the
      rise of delayed hypersensitivity to the parasite antigen are the characteristic
      features associated with the chronicity of the disease. The use of whole
      promastigote as the source of antigens in the direct agglutination test (DAT) and
      immunofluorescent test (IFAT) gave cross-reactions with the sera of leprosy,
      tuberculosis, and African trypanosomiasis patients. Again, the use of cell-free
      extracts of promastigotes generally gave false positive results with the sera of
      normal human and Chagas' disease, leprosy, tuberculosis, and malaria patients in
      enzyme-linked immunosorbent assay (ELISA), dot ELISA, immunodiffusion,
      immunoelectrophoresis, and counter-current immunoelectrophoresis tests.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7639933
TI  - Host-microbe interaction in the gastrointestinal tract.
AB  - In order for an infection to occur, the target organ must come in contact with
      sufficient microbes, the microbe must possess specific virulence factors, these
      virulence factors must be expressed, and the defenses of the organ system must be
      overcome. This dynamic process, which is ongoing in all living entities, can be
      described by the following relationship: [formula: see text] The establishment of
      infection first occurs in a particular organ. This phenomenon is known as tissue
      trophism and the association of microbes with organ systems governs the practice
      of clinical microbiology and infectious disease. With some microbes (e.g.,
      Giardia, Cryptosporidium) the interaction with the particular organ is so
      specific that infections are almost always confined to one site; with others
      (e.g., Salmonella, enterovirus) the microbe has the potential to become systemic.
      When attempting to establish health risk assessment from microbes by contact with
      food and drinking water, one must therefore consider that the gastrointestinal
      tract is a complex organ system with a variety of specific host defense
      mechanisms. It is only when the microbe has particular virulence factors for
      sites in gastrointestinal tract, and the specific host defense mechanisms in the
      gastrointestinal tract are breached, that infection of this organ system occurs.
      Therefore, the general terms "immunosuppression" or "immunocompromise" are
      meaningless unless the specific immune defect is known. A description of the
      microbial virulence factors active against the gastrointestinal tract and the
      defense mechanisms of this organ system are reviewed to provide a biological
      basis health risk assessment and future food and drinking water regulations.

PMID- 7639934
TI  - Effect of delivery on fetal erythropoietin and blood gases in pregnancies with
      maternal diabetes mellitus.
AB  - In 29 pregnancies complicated by maternal diabetes mellitus paired samples of
      umbilical venous blood were obtained at cordocentesis and delivery to investigate
      the effect of delivery on indices of fetal oxygenation. After delivery by
      elective Caesarean section the median umbilical venous blood pH was significantly
      lower than predelivery, however, there was no significant change in the median
      umbilical venous blood pO2 or plasma erythropoietin concentration. In those
      delivered after labour the median umbilical venous blood pH and pO2 were
      significantly lower and the median plasma erythropoietin concentration was
      significantly higher than predelivery. The data of this study demonstrate that
      umbilical venous blood pH and pO2 and plasma erythropoietin are influenced by the
      mode of delivery and results obtained at delivery may not accurately reflect in
      utero homeostasis.

PMID- 7639935
TI  - Helping parents to grieve after second trimester termination of pregnancy for
      fetopathic reasons.
AB  - The main interest in our study was to find out if advice given to facilitate
      mourning after perinatal child loss (looking at the dead child, picture, burial)
      could be used to help parents terminating pregnancies for fetopathic reasons. To
      evaluate the acceptance and to compare the outcome in grief reactions we
      interviewed women undergoing termination of pregnancy for fetopathic reasons 1-2
      days after the loss of the child and they answered a mailed questionnaire 8 weeks
      later. For comparison we assessed data from women with spontaneous child losses
      within the 12th to 24th week of pregnancy in a similar way. No difference in the
      extent of creating memories between the two groups of child losses could be
      assessed (44% of women after termination and 55% after spontaneous loss looked at
      their dead child). Making the dead baby a tangible person led to stronger grief
      reactions immediately after the loss without significant difference due to the
      kind of loss. But 8 weeks later women after spontaneous child losses reported
      significantly more mourning than those after termination. It could be shown that
      women do mourn after termination of pregnancy, that creating memories leads to
      more intense grief reactions shortly after the loss and that grief diminishes
      over time. The advice given to facilitate mourning after perinatal child loss can
      be transferred to parents dealing with termination of pregnancy for fetopathic
      reasons although coping seems to be more complicated in the latter situation.

PMID- 7639936
TI  - Current maternal age recommendations for prenatal diagnosis: a reappraisal using
      the expected utility theory.
AB  - The expected utility theory suggests eliminating an age-specific criterion for
      recommending prenatal diagnosis to patients. We isolate the factors which
      patients and physicians need to consider intelligently in prenatal diagnosis, and
      show that the sole use of a threshold age as a screening device is inadequate.
      Such a threshold fails to consider adequately patients' attitudes regarding many
      of the possible outcomes of prenatal diagnosis; in particular, the birth of a
      chromosomally abnormal child and procedural-related miscarriages. It also
      precludes testing younger women and encourages testing in patients who do not
      necessarily require or desire it. All pregnant women should be informed about
      their prenatal diagnosis options, screening techniques, and diagnostic
      procedures, including their respective limitations, risks, and benefits.

PMID- 7639937
TI  - Endoscopically assisted, ultrasound-guided fetal muscle biopsy.
AB  - Direct endoscopic visualization of in utero fetal muscle biopsy was performed in
      2 cases for which the primary guidance for the procedure remained real time
      ultrasound. Direct visualization aids in the precise placement of the biopsy gun
      which may enable the procedure to be done at earlier gestational ages. At the
      currently used gestational ages (i.e. 18+ weeks), it does not substantially
      improve the procedure.

PMID- 7639938
TI  - Fetal blood sampling and fetal thrombocytopenia.
AB  - The purpose of this investigation is to determine whether fetal thrombocytopenia
      is a risk factor for puncture site bleeding. Three groups of fetuses either with
      or at known risk for thrombocytopenia were identified from a prospectively
      maintained data base of 1,100 procedures: alloimmune thrombocytopenia (ATP, 29
      cordocenteses); unexpected thrombocytopenia (53 cordoncenteses), and
      intravascular transfusion for fetal hemolytic anemia (194 transfusions). A fourth
      group (58 cordocenteses) included as a normal control consisted of all
      appropriately grown fetuses tested within the same gestational age range as those
      with ATP. In total, 276 fetal blood sampling procedures were included, of which
      134 (49%) yielded a platelet count of < 120 x 10(3)/microliters and 38 (14%) a
      platelet count of < 50 x 10(3)/microliters. The first platelet count obtained
      from fetuses with ATP ranged from 1 x 10(3) to 159 x 10(3)/microliters. There was
      no correlation between the platelet count and bleeding time whether the analysis
      was limited to only pretreatment procedures or included all. Each fetus with
      unexpected thrombocytopenia was systemically ill. There was no correlation
      between platelet count and the duration of bleeding from the cord puncture site.
      Intravascular transfusion produced a significant decline in the platelet count
      (238 +/- 66 x 10(3) vs. 153 +/- 56 x 10(3)/microliters, p < 0.001). Twenty-nine
      percent of the post-transfusion platelet counts were below 120 x
      10(3)/microliters. There was a significant negative correlation between the final
      platelet count and the duration of puncture site bleeding (r = -0.178, p = 0.03)
      independent of either the presence of hydrops, the initial or the increase in the
      umbilical venous pressure during transfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7639939
TI  - Single-needle insertion: an alternative technique for early second-trimester
      genetic twin amniocentesis.
AB  - Single-needle insertion as an alternative technique for genetic amniocentesis in
      twin gestation has been evaluated in 27 pregnancies. A 22-gauge needle was
      inserted into the most proximal sac and amniotic fluid was aspirated. The needle
      was then traversed through the dividing membrane to enter the second sac and
      amniotic fluid was aspirated. This technique avoids the use of dye and ensures
      tapping of both sacs. No fetal losses attributable to the procedure occurred
      during the trial. In comparison with the double-needle insertion, it is a swift
      and easy procedure and reduces discomfort to the patient.

PMID- 7639940
TI  - Role of ultrasonography in pregnancies with marker chromosome aneuploidy.
AB  - The objective of this report was to evaluate the effect of ultrasonographic (US)
      findings on pregnancy management in patients with marker chromosome (MC)
      aneuploidy ascertained through prenatal diagnosis. From 1989 through June 1993,
      15,522 prenatal diagnostic procedures were performed for accepted indications.
      Charts of patients with MC on amniocentesis or chorionic villus sampling (CVS)
      karyotype were evaluated with respect to US anomalies, pregnancy complications,
      and outcome. Nineteen cases of MC were identified. The prevalence of MC in our
      study was 0.12% (1:816 procedures). No significant difference between CVS and
      amniocentesis was found: 5/19 (26%) were CVS specimens, which is comparable to
      our CVS (3,259/15,522) case distribution. Three cases with incomplete records
      were excluded from the analysis. Four inherited MC cases were identified: 1 case
      had anencephaly. Of the 12 de novo MC cases 4 (33%) had abnormal US findings, and
      an additional 4 were found to have cytogenetic evidence for partial trisomy.
      Seven of these 8 abnormal de novo MC cases were terminated. MC aneuploidy is more
      common in pregnancies sampled for usual genetic indications than previously
      reported in pediatric series. High-resolution US may identify a major
      malformation not etiologically related to a MC inherited from a normal phenotypic
      parent. The association of the novo MC with US anomalies confers a poor
      prognosis, suggesting the expression of genetic imbalance from the accessory
      chromatin (partial trisomy). However, when US appears normal on initial and
      follow-up examinations, the chances for a normal-phenotypic newborn are high.

PMID- 7639941
TI  - Second trimester selective termination of a twin with ruptured membranes:
      elimination of fluid leakage and preservation of pregnancy.
AB  - Second trimester selective termination has been used for 15 years to prevent the
      birth of children with fetal abnormalities. We have managed a twin pregnancy in
      which one twin had spontaneous rupture of membranes at 15 weeks, with continued
      fluid leakage and oligohydramnios. There was a high risk for infection, and
      selective termination was performed at 18 weeks of gestation, followed by the
      term delivery of the remaining twin. Selective termination may preserve the
      viability of the second twin otherwise considered at high risk for fetal loss.

PMID- 7639942
TI  - Fetal tissue dosages of retinoids. Experimental study concerning a case of
      isotretinoin (Roaccutan) administration and pregnancy.
AB  - The authors report the case of a women who took retinoids (Roaccutan,
      isotretinoin) during the first trimester of pregnancy, and a therapeutic abortion
      was carried out. The interest in this case report lies in the determination of
      the concentration of isotretinoin and its metabolites (4-oxo-isotretinoin, and
      tretinoin) in fetal tissues, using high performance liquid chromatography. The
      findings show the significant transplacental crossing of isotretinoin, an
      accumulation of 4-oxo-isotretinoin in the liver, and a low concentration of
      retinoids in the brain of this 4-month-old fetus. The authors emphasize that
      contraception must be used during retinoid treatment, and 4 weeks after retinoids
      have been stopped.

PMID- 7639943
TI  - Cordocentesis for rapid karyotype: 421 consecutive cases.
AB  - Between October 1985 and December 1993, 421 patients underwent fetal blood
      sampling for rapid karyotyping (426 samplings, 5 twin pregnancies). The aim of
      the study was to evaluate cordocentesis in terms of results, complications and
      additional information in this specific indication especially in case of abnormal
      pregnancy sonogram. The fetal loss rate possibly related to fetal blood sampling
      was 1.9%. Abnormal sonograms represented 91% of rapid karyotype indications.
      Chromosomal abnormalities were found in 9.5% of abnormal sonograms and in 16.9%
      of fetal structural anomalies (37 cases). The commonest chromosomal abnormality
      was trisomy 21 (11 cases). In conclusion, cordocentesis is a safe and reliable
      method for rapid karyotyping although it is associated with more risks than in
      other indications (congenital infections). The high rate of chromosomal
      abnormalities pleaded for ultrasonographic screening in a population usually not
      investigated by cytogenetic studies.

PMID- 7639944
TI  - Transient ascites associated with a fetal ovarian cyst. Case report.
AB  - A case of fetal ovarian cyst associated with transient ascites is presented. The
      cyst showed serial changes from a fluid-debris interface to an anechoic
      structure. The changing ultrasonographic appearance of the cyst, disappearance of
      ascites and postnatal spontaneous resolution, suggests in utero torsion of the
      cyst.

PMID- 7639945
TI  - Fetal-maternal hydrops syndrome in human parvovirus infection.
AB  - A case of maternal generalized edema with hyponatremia, hypoosmolality and
      secondary hyperaldosteronism was associated with pseudomolar plasma human
      chorionic gonadotropin (hCG) concentrations in a case of fetal and placental
      hydrops due to parvovirus B19 infection. Digoxigenin in situ hybridization
      techniques were effective in demonstrating parvovirus B19 infection on fixed
      tissues. Hydropic changes in the placenta may have massively increased the
      maternal plasma hCG concentration with subsequent fluid imbalance leading to
      maternal hydrops mimicking molar pregnancy.

PMID- 7639946
TI  - A case of fetal bradycardia and sinusoid-like fetal heart rate pattern associated
      with maternal hypothermia.
AB  - A 23-year-old pregnant woman presented with severe hypothermia (33.8 degrees C)
      as a complication of treatment for urosepsis. The baseline fetal heart rate was
      100 beats/min. Despite evidence of variability, a 'sinusoid-like' pattern was
      observed. However, the fetal heart rate gradually returned to normal after
      rewarming the patient. This suggests that maternal hypothermia may induce fetal
      bradycardia and a 'sinusoid-like' fetal heart rate pattern.

PMID- 7639947
TI  - Selective serotonin reuptake inhibitors: effects of chronic treatment on ethanol
      reinforced behavior in mice.
AB  - Several lines of evidence suggest that aspects of ethanol drinking are mediated,
      at least in part, by serotonergic (5-HT) neurotransmitter systems. Ethanol
      preferring animals show decreases in serotonin function and receptor densities.
      In addition, serotonin uptake inhibitors have been shown to decrease ethanol
      consumption in animal models and in humans. However, the time course of these
      effects and their duration remain undetermined. In the present studies, C57BL/6J
      male mice were treated with one of three selective 5-HT reuptake inhibitors
      (SSRIs): fluoxetine, sertraline, or paroxetine. All three drugs produced initial
      decreases in operant lever pressing behavior for ethanol followed by a return to
      baseline on subsequent days. Immediately following 14 days of this initial
      treatment, subsequent treatment with higher SSRI doses was ineffective in
      decreasing ethanol-reinforced behavior. However, after a several week "washout
      period," SSRI pretreatment again produced an initial decrease in responding for
      ethanol, again followed by a return to baseline. Thus, suppression of ethanol
      drinking may be related to immediate changes in 5-HT function following treatment
      with SSRIs, and tolerance to this effect appears to develop rapidly.

PMID- 7639948
TI  - Chronic ethanol consumption affects cholinoceptor- and purinoceptor-mediated
      contractions of the isolated rat bladder.
AB  - Isolated bladder strips from 12-week ethanol-fed, pair-fed and control adult male
      rats were investigated. Contractile responses to carbachol (CCh; 0.1-300 microM)
      were statistically significantly potentiated in the ethanol-fed group compared to
      pair-fed and control. Contractions to beta,gamma-methylene ATP (beta,gamma-MeATP;
      1-300 microM) were statistically significantly potentiated in the ethanol-fed
      group at the highest concentration tested (300 microM). Neurogenic contractions
      (0.5-32 pps) from the ethanol-fed group in the absence of atropine and after
      desensitisation by alpha,beta-methylene ATP (alpha,beta-MeATP; 3 microM), were
      significantly potentiated compared to the pair-fed and control groups; in the
      presence of atropine (1 microM), neurogenic contractions were significantly
      augmented at the higher frequencies. It is concluded that chronic ethanol
      treatment affects both cholinoceptor- and purinoceptor-mediated contractions of
      the rat bladder.

PMID- 7639950
TI  - The effect of tropisetron injected into the nucleus accumbens septi on ethanol
      consumption in rats.
AB  - Earlier studies have shown that 5-HT3 antagonists possess properties of reducing
      ethanol (EtOH) preference and intake in EtOH high-preferring rats. In this study
      we examined the effect of tropisetron (ICS 205-930) microinjection (1 and 10 ng)
      into the nucleus accumbens septi (NAS) on EtOH drinking in a scheduled access to
      EtOH paradigm. Control rats received vehicle only. Tropisetron, when injected
      bilaterally into the NAS, significantly reduced EtOH intake in EtOH high
      preferring animals. It is concluded that 5-HT3 antagonists might exert their
      antipreference activity by influencing the receptors within the NAS and that 5
      HT3 receptors might play an important role in reinforcing properties of EtOH.

PMID- 7639951
TI  - Characterization of a GM1-dependent surface interaction for alcohol with DPPC
      membranes.
AB  - A unique surface interaction for perdeuterated ethanol and 1-butanol with
      dipalmitoylphosphatidylcholine (DPPC)/monosialoganglioside (GM1) multilamellar
      vesicles can be detected from the fast exchange averaging of the nuclear
      quadrupole coupling constant of the alcohol in the free and bound states using
      deuterium NMR. At 1.0% perdeuterated ethanol or 0.5% perdeuterated 1-butanol, a
      small splitting of the alcohol resonance(s) was detected in the liquid
      crystalline phase, but not in the gel phase of the bilayer. The observed
      splitting is proportional to the fraction of alcohol bound and is dependent on
      temperature, alcohol, and GM1 concentrations. The splitting was only observed in
      the presence of negatively charged GM1 but not neutral asialoganglioside (asialo
      GM1) in DPPC multilamellar vesicles. The observed splitting decreased with the
      addition of Ca2+ or Mg2+ ions. This effect was reversed upon the addition of
      chelating agents. It is proposed that the unique surface interaction for alcohol
      may result from small surface perturbations of the phosphatidylcholine head
      groups by the negatively charged sialic moieties of neighboring GM1 molecules in
      the bilayer.

PMID- 7639949
TI  - Modification of VLDL apoprotein B by acetaldehyde alters apoprotein B metabolism.
AB  - Acetaldehyde (AcA), the first metabolite in ethanol oxidation, is chemically
      highly reactive and forms adducts with proteins in alcoholics. We examined the
      effect of very low density lipoprotein (VLDL) apoprotein B (apoB) modification by
      AcA on the metabolism of apoB-containing lipoproteins [VLDL, intermediate density
      lipoprotein (IDL) and low density lipoprotein (LDL)]. VLDL-B was selectively
      radiolabelled with either 125I or 131I and modified with various AcA
      concentrations, and the preparation was injected into rabbits simultaneously with
      control-treated VLDL. AcA modification of VLDL-B reduced the fractional catabolic
      rates for VLDL-B, IDL-B, and LDL-B. The direct removal of VLDL-B from plasma was
      decreased, whereas the fraction of VLDL-B converted to IDL-B was increased. The
      effect of AcA modification on the overall fraction of VLDL converted to LDL was
      qualitatively heterogeneous: VLDL-B modification with 2.0 mM AcA reduced the
      fraction converted, whereas modification with 4.0 and 8.0 mM AcA increased it.
      The concentrations of AcA used were higher than those reported in blood after
      ethanol ingestion, but the experiments serve to test in qualitative terms the
      model of VLDL-B modification by AcA. The observed VLDL-B alteration by AcA in
      vivo in alcoholics is most likely to be close to the minor modification used
      here, thereby theoretically contributing to the low IDL and LDL levels observed
      in alcoholics.

PMID- 7639952
TI  - Female Syrian golden hamster: drinking of high concentrations of ethanol aversive
      to other mammals.
AB  - The present experiments were designed to determine: 1) the pattern of preference
      for different concentrations of ethanol in the female Syrian golden hamster
      (Mesocricetus auratus), and 2) the influence of drinking ethanol on their intakes
      of food and total calories. A standard three-bottle preference test was
      undertaken in six female hamsters over an 11-day period in which water was
      offered together with ethanol, which was increased in concentration over 11 days
      from 3% to 50% as follows: 3%, 5%, 7%, 9%, 12%, 15%, 20%, 25%, 30%, 40%, 50%.
      Then, each hamster was offered its individually preferred concentration for a
      period of 8 days until the intake of ethanol had stabilized. During the
      preference testing for 3-25% solutions, the proportional intakes ranged between
      0.6 and 0.8 whereas the mean absolute amount consumed per day increased from 2.3
      to 16.1 g/kg at the 25% concentration. However, at the 50% concentration, ethanol
      drinking declined substantially to 8.7 g/kg per day. The overall mean percent
      concentration of ethanol preferred by the hamsters was 24.2 +/- 1.5%. During the
      following 8-day period when the maximally preferred concentration of ethanol of
      each hamster was offered with water, the mean intake of ethanol was 17.9 +/- 1.1
      g/kg per day. Throughout the test sequence, the caloric intake of the animals was
      maintained in that calories obtained from food declined at the same rate as the
      calories obtained from ethanol in rising concentrations.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7639953
TI  - Gastrectomy enhances vulnerability to the development of alcoholism.
AB  - A history of gastrectomy was more frequently encountered in Japanese male
      alcoholics (9.7%, 47/486) than in male employee populations of two large
      companies (0.8%, 36/4,381, p < 0.001, and 0.6%, 6/950, p < 0.001). Gastrectomized
      men are known to achieve a higher blood ethanol level after the ingestion of the
      equal amount of ethanol than nongastrectomized men. To examine whether or not
      gastrectomy was responsible for the subsequent development of alcohol dependence,
      47 gastrectomized alcoholics were compared with 47 age-matched nongastrectomized
      alcoholics. The mean lifetime duration of heavy drinking (> 120 g ethanol/day)
      was shorter in the former than in the latter (11 +/- 10 years vs. 16 +/- 9, p <
      0.05), and the mean lifetime cumulative ethanol consumption level also smaller
      (834 +/- 497 kg vs. 1047 +/- 508, p < 0.05). The majority of gastrectomized
      patients (30/47) had no history of problem drinking before gastrectomy. The daily
      consumption was rapidly increased within 5 years after gastrectomy in 18 of 38
      habitual drinkers (47%). Seven of the remaining nine nonhabitual drinkers (78%)
      became habitual drinkers and alcoholics within a short period of time (7 +/- 4
      years), though with low lifetime cumulative consumption (< 400 kg). The incidence
      of disorders of the central and peripheral nervous systems observed did not
      differ between the two groups, except for frequent alcoholic blackouts reported
      in the gastrectomized patients. In conclusion, the majority of the gastrectomized
      patients changed their drinking habits after gastrectomy and developed alcohol
      dependence. They did not require as much lifetime cumulative ethanol as
      nongastrectomized patients to become ethanol dependent.

PMID- 7639954
TI  - Ethanol enhancement of the motor-stimulating effect of nicotine in the rat.
AB  - Although ethanol stimulates locomotion in mice, it has been difficult to
      demonstrate such an action in rats. In contrast, nicotine has been shown to
      enhance locomotion, including ipsiversive rotation in nigral-lesioned rats. We
      found no significant effect of ethanol alone on rat rotation at doses of 0.125,
      0.50, 1.0, and 2.0 g/kg, IP, during a 30-min observation period. However, there
      was a dose-dependent effect of ethanol enhancing the rotation induced by nicotine
      (0.4 mg/kg, SC) given 30 min after the ethanol. The interaction of ethanol and
      nicotine on locomotion most likely involves the release of dopamine and may be
      related to the motor abnormalities sometimes seen clinically.

PMID- 7639955
TI  - Sex- and strain-related differences in first-pass alcohol metabolism in mice.
AB  - Adult males and females of three strains of mice, C57BL/10J, C57BL/6J and DBA/2J,
      were intubated or injected intraperitoneally with 0.02 ml/g body weight of a 25%
      alcohol solution. Thirty minutes later, their blood alcohol levels (BAL) were
      measured. Another group of mice, including both sexes, representative of the
      three strains, was fasted for 12 h and sacrificed; their stomachs were removed,
      homogenized, and assayed for gastric alcohol dehydrogenase (GAD) activity. Higher
      BALs were found in all intubated females compared to the intubated males. The
      reverse was observed in the injected group, which showed the males with the
      highest BAL values. GAD activity was evidenced in both sexes of the three strains
      and it was highest in the males. Strain-related differences were evident in the
      intubated groups and not in the injected groups. Intubated DBA animals had the
      lowest BALs as well as the highest GAD values. The results provide evidence for
      first-pass alcohol metabolism in mice and show the effects of sex and strain on
      gastric oxidation of alcohol.

PMID- 7639956
TI  - Antioxidant defense mechanisms in the female rat: interactions with alcohol,
      copper, and type of dietary carbohydrate.
AB  - The purpose of this study was to examine the effects of ethanol, type of dietary
      carbohydrate (fructose vs. starch), and levels of dietary copper (deficient vs.
      adequate) on antioxidant defense mechanism in the female rat. The consumption of
      20% ethanol in the drinking water depressed growth rate due to a reduction of
      feed efficiency. Ethanol also lowered hepatic copper concentration, but had no
      effect on hepatic iron. Among the three antioxidant enzymes studied [i.e.,
      superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase], only
      catalase activity was increased by ethanol. This effect was independent of copper
      or the type of dietary carbohydrate. As expected, copper deficiency dramatically
      reduced SOD. Copper deficiency also reduced GSH-Px activity; however, the
      combination of fructose feeding with copper deficiency caused a further reduction
      in GSH-Px. The data show that copper deficiency, per se, and the combination of
      copper deficiency with fructose feeding lower the antioxidant defense system in
      female rats.

PMID- 7639957
TI  - Ethanol ingestion on allylamine-induced experimental subendocardial fibrosis.
AB  - Effects of ethanol ingestion on allylamine-induced subendocardial fibrosis of the
      myocardium and intimal hyperplasia of the intramyocardial coronary artery were
      investigated in male Wistar rats. The toxic effect of allylamine is ascribed to
      acrolein produced from allylamine by benzylamine oxidase. Animals were forced to
      drink allylamine solution for 12 weeks. Incidence and size of subendocardial
      fibrosis were examined, and the lesions of the intramyocardial artery were
      scrutinized. Effects of ethanol on the systemic blood pressure and benzylamine
      oxidase activity were investigated in another experiment. Treatment with
      allylamine resulted in subendocardial fibrosis (size = 4.2%) in 4 of 12 rats. The
      incidence of fibrosis was increased (up to 6/12) and the area of fibrosis was
      augmented (to 6.8%) in animals additionally treated with epinephrine. The lesions
      in the intramyocardial vasculature were also augmented. Ethanol ingestion reduced
      allylamine-induced subendocardial fibrosis and intramyocardial coronary lesions.
      The effects were significant in animals additionally treated with epinephrine.
      Systemic blood pressure and benzylamine oxidase activity were not significantly
      affected by allylamine or by ethanol. The vasodilatory effect of ethanol may have
      prevented the development of microvascular spasm induced by allylamine.

PMID- 7639958
TI  - Chronic intragastric infusion produces tolerance to ethanol in LS and SS mice.
AB  - Tolerance to ethanol's effects is seen after chronic injections and after chronic
      treatment with ethanol-containing liquid diets. However, tolerance associated
      with injections is often associated with environmental cuing (learned tolerance)
      and liquid diets do not allow for careful control of dose. The studies reported
      here demonstrate that chronic (3 g/kg every 6 h for 7 days) intragastric infusion
      of ethanol produces tolerance to ethanol in both LS and SS mice, as measured by
      sleep time and effects on open field activity and body temperature. LS mice
      developed more tolerance for all measures than the SS. The rate of ethanol
      elimination was increased slightly in both the LS and SS mouse lines following
      chronic ethanol infusion, which suggests that both lines developed a modest
      metabolic tolerance to ethanol. In contrast, the waking blood ethanol levels were
      altered only in the LS mice, which argues that some of the tolerance to ethanol
      seen in the LS mice is pharmacodynamic tolerance. Thus, chronic intragastric
      infusion of ethanol is a reliable method for treating animals chronically with
      ethanol that allows for the precise control of dose and dose interval, oral
      administration of ethanol, and minimal animal handling that can be associated
      with drug delivery, thereby reducing the risk of developing learned tolerance to
      ethanol.

PMID- 7639959
TI  - Alcohols induce rapid depletion of intracellular free Mg2+ in cerebral vascular
      muscle cells: relation to chain length and partition coefficient.
AB  - Acute effects of a series of alcohols (methanol, ethanol, n-butanol) on
      intracellular free magnesium concentration ([Mg2+]i) in canine cerebral vascular
      smooth muscle cells was studied using mag-fura-2 and digital imaging microscopy.
      In 1.2 mM [Mg2+]o, basal [Mg2+]i was 500 +/- 30 microM. Exposure of cells to a
      low concentration (25 mM) of ethanol, but not methanol, for only 30 s resulted in
      significant loss of [Mg2+]i. Exposure to 100 mM methanol, ethanol, and butanol
      for 30 s resulted in a relative order of potency for [Mg2+]i depletion, where
      butanol >> ethanol > methanol. The heterogeneous and relative subcellular
      compartmented concentrations of [Mg2+]i, where perinuclear > nuclear >>
      peripheral (cytosolic) region, was not significantly altered by the alcohols. The
      degree of cellular depletion of [Mg2+]i was directly a function of each alcohol's
      partition coefficient and chain length. The latter is suggestive of the
      probability that alcohols promote intracellular depletion of Mg2+ by partitioning
      in membranes and disordering lipid bilayers.

PMID- 7639960
TI  - Simultaneous changes in striatal dopamine, serotonin, and metabolites after
      withdrawal seizures in rats from dependence on alcohol.
AB  - Ethanol dependence was achieved in male, Long-Evans rats after 8 days on a
      balanced liquid diet that supplied 4.5% ethanol. After 1-h access to a solution
      of 10% ethanol (95%)/5% sucrose, the rats were deprived of food, water, and
      ethanol for 9 h. Following 30-s key jingling, about 80% of the animals exposed to
      ethanol experienced tonic-clonic seizures. Neurochemical analyses of striatal
      tissues revealed a significant (p < 0.05) increase in dopamine (DA) and a
      significant decrease in serotonin (5-HT) in the ethanol-exposed rats that had
      seizures compared to control rats. Homovanillic acid concentrations of the
      ethanol-treated rats with seizures were significantly higher than the levels
      found in ethanol-treated animals that had experienced no seizures. Daily average
      ethanol intake of the rats that had seizures vs. those that did not was almost
      the same at 16 g/kg/day. The findings indicate that rats experiencing ethanol
      withdrawal-induced seizures manifest opposite alterations in dopaminergic and
      serotoninergic activity compared to controls. The present results do not reveal
      if the striatal changes are caused by ethanol rather than by the seizures.

PMID- 7639961
TI  - The effects of acute stress on ethanol absorption in LS and SS mice.
AB  - Previously, our laboratory demonstrated that naive long-sleep (LS) mice absorb
      ethanol faster than short-sleep (SS) mice when administered 6.0 g/kg ethanol
      intragastrically (IG). We also demonstrated that the removal of the adrenal
      glands results in decreased absorption in both lines of mouse. The present study
      was designed to assess whether acute short-term elevations of corticosterone
      produced by exposure to a mild stressor could also alter ethanol absorption in LS
      and SS mice. Because a difference in ethanol absorption rates was observed in LS
      mice as a function of time of day, all stress experiments were performed in the
      morning. CCS elevation was induced by exposure to an elevated plus-maze for 45
      min. LS mice demonstrated greater CCS release in response to this stressor than
      SS mice. This exposure to a mild stressor produced an increase in ethanol
      absorption in both lines of mice receiving a 6.0 g/kg intragastric dose of
      ethanol. Although this effect of stress on ethanol absorption could be prevented
      by adrenalectomy in SS mice, adrenalectomy alone did not completely block these
      effects of stress on ethanol absorption in LS mice. Dexamethasome treatment at
      the time of adrenalectomy was required to block the effects of stress on ethanol
      absorption in LS mice. These results suggest that exposure to mild stressors may
      alter ethanol pharmacokinetic parameters but that genetic factors may play a role
      in this response via regulation of the hypothalamic-pituitary-adrenal axis.

PMID- 7639962
TI  - Ethanol-induced free radical injury to the hepatocyte glucagon receptor.
AB  - Plasma membrane receptors are essential in cellular homeostasis. Free radical
      generation and catalytic iron have been implicated in alcohol-induced liver
      injury; damage to plasma membrane receptors may be one important mechanisms of
      injury. The effect of ethanol-induced free radicals on hepatocyte receptor
      dysfunction was investigated in rodent models of free radical injury due to
      chronic alcohol administration. Receptors for glucagon and their postreceptor
      signal transduction pathway (cyclic AMP production [cAMP]) were investigated as
      sites of free radical injury in isolated perfused livers. Glucagon-stimulated
      cAMP decreased (15%-80%) over a range of physiological (submaximal) doses of
      glucagon after 6 weeks of ethanol feeding, while free radical generation (alkane
      evolution) increased greater than three to fourfold over baseline (ethane; 2.04
      +/- 0.36 vs. 0.58 +/- 0.08 pmole/10(6) cell/hr, p < 0.01; pentane 3.15 +/- 0.30
      vs. 0.91 +/- 0.16, p < 0.01). Iron loading (125 mg/kg IP) potentiated this
      inhibition of cAMP production (40%-95%) and further increased alkane production
      twofold (ethane 4.29 +/- 0.78, pentane 5.76 +/- 0.71). Scatchard analysis
      revealed decreased numbers of glucagon receptors paralleling cAMP responses. Free
      radical damage to hepatocyte cell membrane receptors may be an important
      mechanism of alcohol-induced liver injury.

PMID- 7639963
TI  - Piracetam impedes hippocampal neuronal loss during withdrawal after chronic
      alcohol intake.
AB  - In previous studies we have demonstrated that prolonged ethanol consumption
      induced hippocampal neuronal loss. In addition, we have shown that withdrawal
      after chronic alcohol intake augmented such degenerative activity leading to
      increased neuronal death in all subregions of the hippocampal formation but in
      the CA3 field. In an attempt to reverse this situation, we tested, during the
      withdrawal period, the effects of piracetam (2-oxo-1-pyrrolidine acetamide), a
      cyclic derivative of gamma-aminobutyric acid, as there is previous evidence that
      it might act as a neuronoprotective agent. The total number of dentate granule,
      hilar, and CA3 and CA1 pyramidal cells of the hippocampal formation were
      estimated using unbiased stereological methods. We found out that in animals
      treated with piracetam the numbers of dentate granule, hilar, and CA1 pyramidal
      cells were significantly higher than in pure withdrawn animals, and did not
      differ from those of alcohol-treated rats that did not undergo withdrawal. These
      data suggest that piracetam treatment impedes, during withdrawal, the pursuing of
      neuronal degeneration.

PMID- 7639964
TI  - Acetylcarnitine-mediated inhibition of ethanol oxidation in hepatocytes.
AB  - Carnitine-mediated prevention of ethanol-induced hepatic steatosis is related to
      the attenuation of ethanol metabolism by carnitine in the intact rat. Although
      carnitine retards ethanol oxidation in the intact animal, the in vitro activities
      of ethanol-metabolizing enzymes remain unaltered. Therefore, hepatocytes were
      targeted to understand the mechanism of carnitine effect on ethanol metabolism.
      Rat hepatocytes were isolated by a collagenase-perfusion technique and incubated
      in albumin-containing medium with ethanol in the presence or absence of added
      carnitine or related compounds. Ethanol oxidation was determined by the loss of
      ethanol as well as by the products formed. The rate of ethanol oxidation in the
      presence of carnitine was one-half the rate in the absence of carnitine (14 vs.
      25 nmol.min-1.million-1 cells). It took 100 times the concentration of carnitine
      to equal the maximal inhibition produced by acetylcarnitine and the effect of
      acetylcarnitine was without a lag time. It is concluded that acetylcarnitine is
      the mediator of carnitine inhibition of ethanol oxidation.

PMID- 7639965
TI  - Uncommon invasive mycoses in AIDS.

PMID- 7639966
TI  - Different patterns of HIV-1-specific cytotoxic T-lymphocyte activity after
      primary infection.
AB  - OBJECTIVE: To analyse the HIV-1-specific cytotoxic T-lymphocyte (CTL) responses
      of nine HIV-seropositive subjects in relation with primary infection. METHODS:
      Anti-HIV CTL were generated by in vitro stimulation of peripheral mononuclear
      cells obtained from HIV-seropositive donors at various times after primary
      infection. They were tested against several structural or regulatory HIV-1
      proteins, using autologous target cells infected with recombinant vaccinia
      viruses expressing one of the HIV-1LAI proteins. RESULTS: An important CTL
      activity was found during the first month following seroconversion only in those
      donors who showed clinical symptoms during primary infection. The temporal
      evolution of this response differed for each subject; one remained a non
      responder even 30 months after seroconversion. The structural proteins were
      recognized particularly early, while the antigenicity of regulatory proteins
      appeared later. CONCLUSION: Different patterns of HIV-specific CTL response can
      be observed after primary infection. The evolution of infection in these
      different HIV-seropositive subjects will be particularly interesting to analyse.

PMID- 7639969
TI  - Reduced toxoplasmastatic activity of monocytes and monocyte-derived macrophages
      from AIDS patients is mediated via prostaglandin E2.
AB  - OBJECTIVE: To establish the role of prostaglandin E2 (PGE2) formed and released
      by monocytes and monocyte-derived macrophages (MDM) in the reduced
      toxoplasmastatic activity of these cells. DESIGN: Determination of PGE2 levels in
      the serum of AIDS patients, the release of PGE2 by monocytes and MDM from AIDS
      patients, the toxoplasmastatic activity of these cells and the effect of
      indomethacin, an inhibitor of PGE2 synthesis, on this cell function. SETTING:
      Laboratory of Cellular Immunology of the Department of Infectious Diseases,
      University Hospital, Leiden. PARTICIPANTS: Twenty-six AIDS patients. Healthy
      blood donors served as controls. RESULTS: The concentration of PGE2 in the serum
      from AIDS patients was significantly higher compared with serum from controls.
      Non-stimulated monocytes and lipopolysaccharide-stimulated monocytes and MDM from
      AIDS patients released significantly more PGE2 than corresponding cells from the
      controls. The proliferation of Toxoplasma gondii in monocytes and MDM from AIDS
      patients was significantly higher than in the respective cells from controls.
      Preincubation of these cells with indomethacin resulted in a decreased
      proliferation of T. gondii in non-activated monocytes and MDM and in interferon
      gamma-activated MDM from AIDS patients. Preincubation of monocytes from healthy
      donors with PGE2 resulted in a dose-dependent increase of Toxoplasma
      proliferation which confirms that PGE2 can reduce the toxoplasmastatic activity
      of monocytes. CONCLUSION: PGE2 is involved in the reduced toxoplasmastatic
      activity of monocytes and MDM from AIDS patients.

PMID- 7639967
TI  - Viral phenotype and host-cell susceptibility to HIV-1 infection as risk factors
      for mother-to-child HIV-1 transmission.
AB  - OBJECTIVE: To investigate the role of maternal HIV-1 isolate phenotype and a
      child's cell susceptibility/resistance to viral infection in mother-to-child HIV
      1 transmission. PATIENTS AND METHODS: Forty-nine women were studied at the time
      of delivery. Primary isolates, obtained by culturing patient peripheral blood
      mononuclear cells (PBMC) with PBMC from healthy donors, were characterized for
      tropism and syncytium-inducing capability in monocyte-derived macrophages (MDM),
      peripheral blood lymphocytes (PBL), and in the MT-2 and MOLT-3 T-cell lines.
      RESULTS: Seven women transmitted HIV-1 to their children. Primary isolates were
      obtained from six and 28 transmitting and non-transmitting mothers, respectively.
      All primary isolates from transmitting mothers and their infants but only 50% of
      those from non-transmitting mothers replicated in MDM, regardless of their
      replication capacity in T-cell lines. PBL and MDM cells from six uninfected
      children were exposed to the corresponding maternal isolates. Polymerase chain
      reaction analysis of HIV-1 DNA in cells and p24 antigen assay in culture
      supernatants disclosed that two PBL and five MDM cultures were resistant to viral
      infection; two other PBL cultures, although HIV-1-infected, were negative for p24
      production. Depletion of CD8+ cells only partially restored productive infection
      in CD4+ cell cultures. Moreover, all six PBL but only one MDM cultures were
      productively infected by an isolate obtained from a transmitting mother, thus
      suggesting that MDM resistance to HIV-1 infection is not viral isolate
      restricted. CONCLUSIONS: Our findings strongly suggest that mother-to-child HIV-1
      transmission is influenced by both monocyte-macrophage tropism of the maternal
      isolate and susceptibility of the child's target cells, in particular monocyte
      macrophages, to HIV-1 infection.

PMID- 7639968
TI  - Simultaneous introduction of distinct HIV-1 subtypes into different risk groups
      in Russia, Byelorussia and Lithuania.
AB  - OBJECTIVE: To investigate genotypes and serotypes of HIV-1 variants in Russia,
      Byelorussia and Lithuania. PATIENTS AND METHODS: Sera from 20 HIV-1-infected
      individuals were tested in an enzyme-linked immunosorbent assay (ELISA) with 19
      V3 synthetic peptides, and serum HIV-1 V3 RNA was amplified and sequenced.
      RESULTS: Sequence comparison of the envelope V3 region among specimens tested
      revealed a 2-29% range nucleotide divergence, with a mean of 19%. Phylogenetic
      analysis from the homosexual men were shown to belong to subtype B, and all of
      the heterosexually infected individuals to subtype C. Sequences from the
      parenterally infected individuals were more heterogeneous. IOn the peptide ELISA
      three reactivity patterns were found. Serum samples from six out of seven
      homosexual men showed reactivity to peptides p108 or p110 representing V3 amino
      acid sequences found in US/West European HIV-1 isolates. Serum samples from six
      of seven individuals who had acquired HIV-1 through heterosexual contacts were
      reactive to peptide p169. Four out of six parenterally infected patients had peak
      reactivity to p168. CONCLUSION: Distinct HIV-1 variants were found in Russia,
      Byelorussia and Lithuania, which were introduced simultaneously in the mid-1980s.
      This diversity was shown to be associated with the route of transmission.
      Homosexual men appeared to be infected with subtype B and heterosexually infected
      individuals with subtype C HIV-1 variants. HIV-1 subtypes A, C, D and G were
      found among parenterally infected individuals.

PMID- 7639970
TI  - Onset of clinical signs in children with HIV-1 perinatal infection. Italian
      Register for HIV Infection in Children.
AB  - OBJECTIVE: To investigate the timing of onset of each clinical sign in infants
      and children with HIV-1 perinatal infection. DESIGN AND METHODS: A total of 200
      HIV-1-infected children followed-up from birth were studied. Failure and
      conditional probabilities were estimated by the Kaplan-Meier product-limit
      method. Cox proportional hazard analysis was used to evaluate independently
      associated factors. Results of 934 seroreverters were used to calculate reference
      values of CD4+ cell counts and predictivity of early signs. RESULTS: Median age
      at the onset of any sign was 5.2 months (range, 0.03-56 months). The probability
      of remaining asymptomatic was 19% [95% confidence interval (CI), 14-25.1] at 12
      months and 6.1% (95% CI, 2.6-11.7) at 5 years. Lymphadenopathy (69.5%),
      splenomegaly (62.4%) and hepatomegaly (58.4%) were the most common signs in the
      first year of life. Peculiar to the first year of life (compared with subsequent
      ages) was the onset of primary HIV-1 hepatitis and diarrhoea (rate ratios, 23.3
      and 15.2, respectively). When CD4+ cell counts in the asymptomatic stage (age, 2
      months; range, 0.03-5.9 months) were below rather than above the fifth percentile
      in seroreverters, onset of signs was earlier [3 range, 0.03-19) versus 5 (range,
      0.03-56) months]. Children manifesting signs before the 5.2-month breakpoint had
      a lower survival rate [74% (range, 65.9-82%) at 12 months and 45% (range, 32.9
      57%) at 5 years] than children manifesting signs later [98% (range, 92.2-100%) at
      12 months and 74% (range, 60.3-87.7%) at 5 years]. Children whose birthweight was
      < or = 2400 g had an earlier onset (24 months; range, 1-57 months) of severe
      conditions than children with higher birthweight (71 months; range, 1-71 months).
      Development of lymphadenopathy or hepatosplenomegaly within 3 months of life were
      reliable indicators of infection. CONCLUSIONS: This study describes the sequence
      of onset of signs in perinatal HIV-1 infection. Infection is shown to progress
      faster than in adults and in a different manner. Low birthweight, early decreased
      CD4+ cell counts, and early onset of signs are predictive of rapid progression.

PMID- 7639971
TI  - A dose comparison study of didanosine in patients with very advanced HIV
      infection who are intolerant to or clinically deteriorate on zidovudine. German
      ddI Trial Group.
AB  - OBJECTIVE: Zidovudine (ZDV) is the only antiretroviral drug which has been shown
      to reduce mortality in patients with symptomatic HIV disease, but its use is
      restricted by intolerance in a significant proportion of patients. Additionally,
      the efficacy of ZDV therapy appears to decrease after prolonged treatment
      particularly in the advanced stage of HIV disease. Therefore, alternative
      antiretroviral regimens for patients are needed. In this study, didanosine (ddI;
      2',3'-dideoxyinosine), another HIV reverse transcriptase inhibitor, was
      evaluated. DESIGN: A total of 426 patients with AIDS or AIDS-related complex
      (ARC) who were intolerant to or clinically progressing on ZDV therapy and who had
      CD4+ cell counts < or = 150 x 10(6)/l were randomized to receive either a high
      (750 mg for bodyweight > or = 60 kg or 500 mg for bodyweight < 60 kg) or a low
      (200 mg and 134 mg, respectively) dose of ddI daily. SETTING: The patients were
      recruited from 31 German and Austrian AIDS clinical primary-care centres.
      RESULTS: The study was stopped after the second interim analysis due to a
      statistically significant difference in the incidence of pancreatitis (nine
      versus 26; relative risk, 2.92; P = 0.003) and neuropathy (28 versus 43; relative
      risk, 1.55; P = 0.05) in favour of the low dose. There was no difference between
      the low and high dosage groups in survival rate at 6 (80 versus 80%) and 12
      months (61 versus 65%), number of deaths [82 (43.6 per 100 patient-years) versus
      84 (44.4 per 100 patient-years)], progression from ARC to AIDS or to AIDS or
      death, or average number of new/recurrent opportunistic infections (2.8 versus
      3.0 per patient). CONCLUSIONS: This study cannot conclude on ddI efficacy but it
      shows that in patients with advanced HIV disease for whom no alternative
      antiretroviral therapy is available and ddI therapy is considered, daily doses <
      750 mg should be administered.

PMID- 7639972
TI  - Intravenous versus oral ganciclovir: European/Australian comparative study of
      efficacy and safety in the prevention of cytomegalovirus retinitis recurrence in
      patients with AIDS. The Oral Ganciclovir European and Australian Cooperative
      Study Group.
AB  - OBJECTIVES: To evaluate the efficacy and safety of oral ganciclovir for the
      maintenance treatment of cytomegalovirus (CMV) retinitis in patients with AIDS.
      DESIGN: A 20-week, randomized, multicentre, open-label study. Progression of
      retinitis was assessed by funduscopy and masked reading of fundus photographs.
      METHODS: Adult patients with AIDS and stable CMV retinitis following a 2-3 week
      induction course of intravenous ganciclovir (5 mg/kg every 12 h) were randomized
      2:1 to receive maintenance therapy with oral ganciclovir 500 mg six times daily,
      or 5 mg/kg intravenous ganciclovir once daily infused over 1 h. The primary
      efficacy variable was time to progression of CMV retinitis from initiation of
      maintenance therapy. RESULTS: A total of 159 patients were enrolled; 112 received
      oral ganciclovir and 47 intravenous ganciclovir. By masked assessment of fundus
      photographs, CMV retinitis progressed in 72% of patients in the oral group and
      76% in the intravenous group. Mean time to progression was 51 days with oral
      ganciclovir and 62 days with intravenous ganciclovir (P = 0.15). By funduscopy,
      CMV retinitis progressed in 59% of oral ganciclovir patients and 43% of
      intravenous ganciclovir patinets. Mean time to progression was 86 and 109 days,
      respectively (P = 0.02). Diarrhoea and neutropenia (absolute neutrophil count <
      500 x 10(6)/l) were the most frequently reported adverse events in both groups.
      The incidence of spesis for the oral and intravenous ganciclovir patients was 3
      and 8.5%, respectively. Infection at the intravenous site occurred in 0 and 9% of
      patients, respectively. CONCLUSIONS: Oral ganciclovir offers an effective and
      safe alternative to intravenous ganciclovir in the maintenance therapy of CMV
      retinitis.

PMID- 7639973
TI  - Behavioural interventions for HIV/AIDS prevention.
AB  - OBJECTIVES: The aim of this study was to identify and critically review
      behavioural interventions in the HIV prevention and sexual health fields.
      METHODS: Electronic and hand searches were conducted to retrieve relevant
      published and unpublished reports of outcome evaluations. A methodological review
      was carried out to identify those with sufficient methodological strengths to
      generate reliable conclusions as to effectiveness. Soundly designed studies were
      defined as those which met the four core criteria of employing control groups,
      providing pre- and post-intervention data and reporting on all targeted outcomes.
      RESULTS: A total of 68 separate reports of outcome evaluations were located. Only
      18 were judged to be methodologically adequate. Major problems found were lack of
      a control group or non-equivalent/unbalanced control groups, small sample sizes,
      failures to report pre-intervention measures, short follow-up, and high attrition
      rates. Academic reviewers were more likely than the authors of papers to judge
      reports of evaluations as providing insufficient information to assess
      effectiveness. CONCLUSION: Evaluation design in this field needs to be improved.
      Recommendations include more use of randomized controlled trials and the raising
      of publication standards by journals.

PMID- 7639974
TI  - HIV testing patterns: where, why, and when were persons with AIDS tested for HIV?
AB  - OBJECTIVE: To describe the location of, primary reason for, and time between the
      first positive HIV test and AIDS diagnosis in a sample of persons with newly
      diagnosed AIDS. DESIGN: Interviews supplementing information routinely collected
      through AIDS case reporting. SETTING: Eleven US states and cities. PATIENTS:
      Persons with AIDS (2441) diagnosed between January 1990 and December 1992. MAIN
      OUTCOME MEASURES: Location of first positive HIV test, primary reason for
      testing, and time interval between first positive HIV test and AIDS diagnosis.
      RESULTS: Overall, persons were tested late in their course of HIV infection: 36%
      were tested for HIV within 2 months and 51% within 1 year of their AIDS
      diagnosis. Sixty-five per cent were HIV-tested in acute health-care settings: 33%
      in hospitals, 28% in physicians' offices, and 4% in emergency departments.
      Testing during hospitalization was most common among injecting drug users (43%)
      and persons infected through heterosexual contact (50%). Persons primarily sought
      HIV testing because of illness (58%); other reasons included being in a known
      risk group (13%) and having had a known HIV-infected sex partner (8%). Testing
      because of being in a known risk group was least common among persons infected
      through heterosexual contact (1%). Among persons in these exposure categories,
      testing differed by race/ethnicity. CONCLUSION: Most persons with AIDS were
      tested relatively late in their course of HIV infection, in acute health-care
      settings, and because of illness. Not knowing one's serostatus precludes early
      medical intervention and may increase transmission.

PMID- 7639975
TI  - Changes in the injecting risk behaviour of injecting drug users in London, 1990
      1993.
AB  - OBJECTIVE: To describe changes in the injecting risk behaviour of injecting drug
      users (IDU) in London between 1990 and 1993. DESIGN: Injecting risk behaviour was
      measured over 4 years (1990-1993) in a serial point HIV prevalence study of 2062
      IDU recruited in both drug treatment and non-treatment community-based settings
      within greater London. The study used a structured questionnaire and common
      sampling and interview strategy developed by a World Health Organization
      technical group and implemented in 13 cities. METHODS: Log-linear models were
      used to assess patterns of change over years and of differences in injecting risk
      behaviour, including syringe sharing and syringe hygiene between 1990 and 1993.
      The log likelihood chi 2 statistic, G2, was used to test statistical
      significance. Changes in the mean values were assessed first using parametric
      tests assuming normality and the results were compared with Kruskal-Wallis (non
      parametric) tests. Pearsons chi 2 was used to measure differences in frequency of
      sharing occasions and partner selectivity. RESULTS: An overall reduction in
      injecting risk behaviour was observed during the first 2 years of this study,
      including a decline in syringe sharing (both accepting and passing on used
      syringes), the number of sharing partners and the frequency of sharing occasions.
      Most sharers restricted sharing to sexual partners and close friends. The
      majority of sharers reported always cleaning injecting equipment. Main source of
      sterile equipment was pharmacies and syringe exchanges. Indirect sharing (of
      spoons, filters, and by front- or backloading) was reported. Since 1991 there has
      been a stabilization in risk behaviour. CONCLUSIONS: The data indicate that IDU
      in London have made positive reductions in risk behaviour. Levels of syringe
      sharing were substantially lower than those reported up to 1987 before AIDS
      awareness and the introduction of HIV prevention measures. The majority did not
      share syringes or confined their sharing to close friends and sexual partners,
      and if shared, cleaned their syringes. Continuation of indirect sharing indicates
      the need for more detailed prevention messages. While the initial decline in
      syringe-sharing rates may be attributed to the wide availability of sterile
      injecting equipment and other preventive measures, it may now be necessary to
      look beyond current intervention initiatives to develop interventions which seek
      to change the social etiquette of sharing and move towards the long-term
      maintenance of low levels of injecting risk behaviour.

PMID- 7639976
TI  - Migration and HIV-1 seroprevalence in a rural Ugandan population.
AB  - OBJECTIVE: To study the association between change of residence and HIV-1
      serostatus in a rural Ugandan population. DESIGN: A longitudinal cohort study.
      METHODS: As part of the annual surveillance of a population cohort of
      approximately 10,000 individuals in a rural subcounty of southwest Uganda,
      information has been collected for all adults on change of residence over a 3
      year period and its association with HIV-1 serostatus. Sera were collected by a
      medical team during home visits. Antibody testing was performed at the Uganda
      Virus Research Institute using two independent enzyme immunoassay systems and
      Western blot when appropriate. RESULTS: At the fourth survey-round, age and sex
      standardized seroprevalence rates were 7.9% overall; the rate was 5.5% for 2,129
      adults who had not changed address since the first survey, 8.2% for 336 who moved
      within the village, 12.4% for 128 who moved to a neighbouring village, 11.5% for
      1,130 who had left the area and 16.3% for 541 who had joined the study area
      during the previous 3 years (P << 0.001, 4 degrees of freedom). We also observed
      an inverse relationship between years lived at the present house at the time of
      the first survey and both seroprevalence and subsequent seroincidence rates. The
      reported numbers of lifetime sexual partners were higher in those who changed
      residence. CONCLUSION: Change of residence is strongly associated with an
      increased risk of HIV-1 infection in this rural population and is likely to be
      the result of more risky sexual behaviour among those who move. These findings
      have important implications for the design of AIDS control programmes and
      intervention studies.

PMID- 7639977
TI  - The relational determinants of condom use with commercial sex partners in
      Thailand.
AB  - OBJECTIVE: To analyze the extent and determinants of condom use with commercial
      sex partners among lower socioeconomic status groups in the Thai population.
      DESIGN: Respondents were sampled in Udon Thani, Saraburi and Bangkok in 1992.
      Completed sample size was 678 women in brothels, 330 male truck drivers and 1,075
      men aged 17-45 years. Behavioral data and local sexual network information were
      collected using structured questionnaires (face-to-face interviews), focus groups
      and in-depth unstructured interviews. METHODS: Data were analyzed using
      univariate and multivariate logistic regression. RESULTS: Condom use with
      commercial partners remains inconsistent. Consistent use was reported by 61% of
      women in brothels, 25% of truck drivers, and 29% of men in the low-income
      population. The single strongest predictor of consistent condom use for all
      groups is type of partnership. Consistent use drops significantly with regular
      (multivisit) commercial sex partners compared with casual (single visit)
      commercial partners; adjusted odds of consistent use are 0.22 for women and 0.25
      for men. Brothel women report that one in five of their commercial partners is a
      'regular', and 20% of the young men who report a commercial partner report a
      'regular'. DISCUSSION: The strongest determinant of consistent condom use is the
      nature of the relational bond between the partners, rather than their individual
      characteristics, knowledge or attitudes. To raise condom use further, programs
      will have to move beyond the standard knowledge-attitudes-practices paradigm
      focus on individual attributes to address the contextual determinants of
      behavior.

PMID- 7639979
TI  - Condom use in Thailand: how much is it slowing the HIV/AIDS epidemic?

PMID- 7639978
TI  - The epidemiology of HIV and syphilis among male commercial sex workers in
      northern Thailand.
AB  - OBJECTIVE: To examine the prevalence and incidence of HIV and syphilis, and risk
      behaviors for these infections, among 1,172 male commercial sex workers (CSW)
      followed prospectively from 1989 to 1994 in Chiang Mai, northern Thailand.
      METHODS: Twice yearly visits were conducted by the Thai Ministry of Public Health
      at all cooperating gay bars and clubs (17 sites) in Chiang Mai City as part of a
      national HIV sentinel surveillance. Men and boys who agreed were followed
      prospectively. Sentinel visits included an interview, HIV pre-test counseling,
      HIV and syphilis serology, condom distribution, and referral for post-test
      counseling. Participation was voluntary, confidential, and individual HIV results
      were available only to participating subjects. A total of 219 CSW were seen at
      least twice, allowing for incidence estimates based on 100 person-years (PY).
      RESULTS: Median age of male CSW was 20 years. Median time of work as a CSW was 4
      months. Most men (57.6%) described themselves as heterosexual. Median number of
      clients was 2.5 per week, and reported condom use with clients was low: 42%
      reported inconsistent or no condom use, while 58% reported always using condoms.
      Reactive Venereal Disease Research Laboratory results were 7.6%, overall, but
      showed a declining trend. HIV prevalence was 1.4% in June 1989, 13.9% in June
      1990, and 20.1% in December 1993, and showed a significant increasing trend.
      There were 27 incident HIV infections in 227.3 PY of observation, for an overall
      incidence during the 4.5-year period of 11.9 per 100 PY (95% confidence interval,
      7.42-16.38). CONCLUSION: Male CSW in northern Thailand are at high risk for HIV
      despite current prevention efforts. The majority are heterosexual, which may be
      an important epidemiologic link in the spread of HIV between male CSW users and
      heterosexual women in Thailand.

PMID- 7639981
TI  - Kinetics of detection of antibodies to HIV-1 and plasma p24 antigens during a
      severe primary HIV-1 infection.

PMID- 7639980
TI  - Failure to infect lower primate species with SIVcpz.

PMID- 7639982
TI  - Comparison of the rates of CD4 count decline among HIV-infected women and men.

PMID- 7639984
TI  - Cytomegalovirus encephalitis resistant to anti-cytomegalovirus therapy.

PMID- 7639983
TI  - ABO blood groups and rhesus group antigens in epidemic Kaposi's sarcoma.

PMID- 7639985
TI  - Thrombotic thrombocytopenic purpura and haemolytic uraemic syndrome in HIV
      infected patients.

PMID- 7639986
TI  - Azole-resistant oropharyngeal and esophageal candidiasis in patients with AIDS.

PMID- 7639988
TI  - Severe ulcers from an unconventional therapy against AIDS.

PMID- 7639987
TI  - Papular mucinosis in HIV-infected patients.

PMID- 7639989
TI  - Condom promotion strategies: what we need to know?

PMID- 7639990
TI  - Bacillus cereus and Bacillus thuringiensis isolated in a gastroenteritis outbreak
      investigation.
AB  - During investigation of a gastroenteritis outbreak in a chronic care institution,
      Norwalk virus was found in stool specimens from two individuals and bacterial
      isolates presumptively identified as Bacillus cereus were isolated from four
      individuals (including one with Norwalk virus) and spice. Phage typing confirmed
      all Bacillus clinical isolates were phage type 2. All clinical isolates were
      subsequently identified as B. thuringiensis when tested as a result of a related
      study (L. Leroux, personal communication). Eight of 10 spice isolates were phage
      type 4. All B. cereus and B. thuringiensis isolates showed cytotoxic effects
      characteristic of enterotoxin-producing B. cereus. An additional 20 isolates each
      of B. cereus and B. thuringiensis from other sources were tested for
      cytotoxicity. With the exception of one B. cereus, all showed characteristic
      cytotoxic patterns.

PMID- 7639991
TI  - Assessment of rapid bioassays for detecting cyanobacterial toxicity.
AB  - Simple and easy-to-use bioassays with Artemia salina (brine shrimp) larvae,
      luminescent bacteria and Pseudomonas putida were evaluated for the detection of
      toxicity due to cyanobacterial hepato- and neurotoxins. The hepatotoxins and a
      neurotoxin, anatoxin-a, were extracted from laboratory-grown cultures and natural
      bloom samples by the solid phase fractionation method and dissolved in diluent
      for different bioassays. The toxin concentration of cyanobacterial extracts was
      determined with HPLC. The Artemia biotest appeared to be quite sensitive to
      cyanobacterial hepatotoxins, with LC 50 values of 3-17 mg l-1. The Artemia test
      was also shown to be of value for the detection of toxicity caused by anatoxin-a.
      The fractionated extract of anatoxin-a was not lethal to Artemia but it disturbed
      the ability of the larvae to move forwards. Filtered cyanobacterial cultures with
      anatoxin-a, on the other hand, caused mortality of Artemia larvae at
      concentrations of 2-14 mg l-1. With the solid phase fractionation of
      cyanobacterial samples, no non-specific toxicity due to compounds other than
      hepato- and neurotoxins was observed. In the luminescent bacteria test, the
      inhibition of luminescence did not correlate with the abundance of hepatotoxins
      or anatoxin-a. The growth of Ps. putida was enhanced, rather than inhibited by
      cyanobacterial toxin fractions.

PMID- 7639992
TI  - Effects of chlorhexidine gluconate on the development of spores of Bacillus
      subtilis.
AB  - The effects of sublethal concentrations of the membrane-active agent
      chlorhexidine gluconate (CHG) on the growth rate and sporulation of Bacillus
      subtilis vegetative MB2 cells have been investigated. CHG increased the mean
      generation time (Mgt) of vegetative cells in casein medium. It also affected
      spore development: as CHG concentrations increased, spore index (SI) values
      decreased and sensitivity to both toluene and heat increased.

PMID- 7639993
TI  - Inhibitory effect of selected lactic acid bacteria on microflora associated with
      ready-to-use vegetables.
AB  - The addition of selected lactic acid bacteria strains had a remarkable inhibitory
      effect on the growth dynamics of microflora associated with ready-to-use
      vegetables, during refrigerated storage. In particular, coliforms and enterococci
      were strongly reduced or eliminated from the products from the third day of
      storage. Lactobacillus casei strains proved more effective than pediococci. The
      use of lactic cultures able to produce bacteriocins and to grow at low
      temperatures could be a useful tool to preserve fresh vegetables and to ensure
      their microbiological safety.

PMID- 7639994
TI  - Czapek casein 50% glucose (CZC50G): a new medium for the identification of
      foodborne Chrysosporium spp.
AB  - A new medium Czapek Casein 50% Glucose agar (CZC50G) has been developed, on which
      the four foodborne Chrysosporium spp., C. xerophilum, C. inops, C. farinicola and
      C. fastidium can be distinguished by differences in growth rates and colony
      morphology. Chrysosporium xerophilum and C. inops both produced dense white
      colonies, but C. xerophilum grew faster than C. inops, 22 mm in 14 d compared to
      9-12 mm in 14 d at 25 degrees C. Some isolates produced a yellow or red reverse
      due to the reaction of ferric ammonium citrate incorporated in the medium with a
      fungal metabolite. Chrysosporium farinicola and C. fastidium both grew poorly on
      this medium and produced sparse colonies: C. farinicola grew faster. Electron
      micrographs of arthroconidia with a cryo-scanning electron microscope showed
      thickening of the spore walls in C. inops but not in C. xerophilum. The
      aleurioconidia of C. farinicola and C. fastidium were different in shape. The
      differences in colony morphology and growth rate on CZC50G reflected these
      differences and demonstrated that these four species could be distinguished
      easily on CZC50G.

PMID- 7639995
TI  - A defined medium for rumen bacteria and identification of strains impaired in de
      novo biosynthesis of certain amino acids.
AB  - A completely defined growth medium has been developed to determine the nitrogen
      requirements for several species of ruminal bacteria, and has revealed two
      strains which are impaired in de novo biosynthesis of certain amino acids. Using
      NH4Cl as a sole nitrogen source, the medium supported growth of Butyrivibrio,
      Selenomonas, Prevotella and Streptococcus species. One strain of B. fibrisolvens
      (E14) and one strain of P. ruminicola (GA33) did not grow in the presence of
      NH4Cl until the medium was supplemented with amino acids or peptides. For B.
      fibrisolvens strain E14, methionine was identified as the specific growth
      limiting amino acid although methionine alone did not support growth in the
      absence of NH4Cl. For P. ruminicola strain GA33, any individual amino acid other
      than methionine or cysteine could supplement the medium and support growth.
      Enzyme assays confirmed a lack of NADH and NADPH-dependent glutamate
      dehydrogenase (GDH) activities in this strain.

PMID- 7639996
TI  - Molecular analysis of Japanese isolates of Verticillium dahliae and V. albo
      atrum.
AB  - Sixteen isolates of different pathogenicity groups of the plant pathogen
      Verticillium dahliae and four isolates of V. albo-atrum from Japan were analysed
      by means of an RAPD (random amplified polymorphic DNA) method using a PCR
      (polymerase chain reaction). Verticillium dahliae and V. albo-atrum could be
      distinguished by RAPD analysis. Four pathogenicity groups of V. dahliae could
      also be classified to a certain extent by this method. Similarities and
      differences in banding patterns obtained by RAPD may be a useful molecular tool
      in phylogenetic studies of the pathogenicity groups.

PMID- 7639997
TI  - Evaluation of the TECRA Escherichia coli O157 visual immunoassay for tests on
      dairy products.
AB  - The TECRA visual immunoassay was compared with an enrichment plating procedure
      according to the United States Food and Drug Administration procedures, for the
      detection of Escherichia coli in dairy foods. Both methods were used to detect E.
      coli O157 which had been inoculated into cheeses, milk powders, caseins and whey
      products. A centrifugation step was needed to test whey products according to the
      TECRA method. The results from both test methods were in complete agreement.

PMID- 7639998
TI  - Construction of species-specific primers for Pseudomonas andropogonis based on
      16S rDNA sequences.
AB  - Approximately 94% of the total 16S rDNA of Pseudomonas andropogonis strain ACH
      01053A was sequenced and compared with that of strain ATCC 23061 obtained from
      the GenBank database. The two sequences were highly homologous with 1.3%
      difference. Alignment of sequences with those from closely related bacteria
      revealed two possible regions for design of a specific primer suitable for
      detection of Ps. andropogonis. Using primers designed to these variable regions
      in a PCR test, an amplification product of approximately 410 bp was specifically
      produced by 40 strains of Ps. andropogonis. No other bacterial species showed an
      amplification product under optimized PCR conditions. As few as 1000 cells per
      reaction were detected.

PMID- 7639999
TI  - Escherichia coli JA221 can suppress the UAG stop signal.
AB  - The Escherichia coli strain JA221 can suppress the UAG stop codon, although the
      existence of an amber suppressor tRNA has not previously been described for this
      strain. When using a plasmid to express alpha-sarcin, which has TAG as its stop
      signal, two proteins were obtained: a smaller protein corresponding in size to
      that of the expected protein, and a larger protein, which could be accounted for
      by the presence of a second stop codon (TGA) 18 base pairs downstream of the
      original. This feature of strain JA221 must therefore be considered when using
      this strain as a host for the production of recombinant proteins.

PMID- 7640000
TI  - Beta-D-galactosidase activity of viable, non-culturable coliform bacteria in
      marine waters.
AB  - The beta-D-galactosidase activity of viable but non-culturable (vnc) Escherichia
      coli cells in seawater was investigated using a rapid fluorimetric enzyme assay.
      Results from microcosm studies showed that loss of culturability did not
      necessarily result in loss of the ability to produce the galactosidase enzyme.
      Even when no culturable cells were detected, a positive enzyme assay response was
      observed and the activity of the inducible enzyme over time more closely
      reflected the number of vnc cells present.

PMID- 7640001
TI  - Effect of growth environment on the stability of a recombinant shuttle plasmid,
      pCPPS-31, in Escherichia coli.
AB  - The effect of environmental growth conditions on the segregational stability of a
      recombinant Escherichia coli-Bacillus subtilis shuttle plasmid pCPPS-31 which
      expresses carboxymethyl cellulase (CMCase) and contains the neomycin resistance
      gene (Ner), was studied in E. coli DH5 alpha. The stability increased with the
      decrease in medium complexity. Lowering culture temperatures had a negative
      effect on stability. Stability was maximum at 100 rpm and a medium/flask volume
      ratio of 1:10. A pH range of 5-8 had no significant effect on stability. The
      recombination (rec) and gyrase (gyr) backgrounds of E. coli hosts had no apparent
      effect on plasmid stability. The plasmid was structurally stable under all
      circumstances.

PMID- 7640002
TI  - A new design intended to relate high pressure treatment to yeast cell mass
      transfer.
AB  - A new optical device has been developed to allow the observation of
      microorganisms during a high pressure treatment up to 700 MPa. To measure cell
      volume variation during the high pressure application, an image analysis system
      was connected with the light microscope. With this device, growth of
      Saccharomyces cerevisiae was studied at moderate pressure (10 MPa) through the
      observation of individual cell budding. Cell volume variations were also measured
      on the yeast Saccharomycopsis fibuligera on fixed cells as well on a population
      sample and a shrinkage in average cell volume was observed consequently to a
      pressure increase of 250 MPa. The observed compression rate (25%) under pressure
      and the partial irreversibility of cell compression (10%) after return to
      atmospheric pressure lead to the conclusion that a mass transfer between cell and
      cultivation medium occurred. The causes of this transfer could be explained by a
      modification of membrane properties, i.e., disruption or increase in
      permeability.

PMID- 7640003
TI  - Penicillium purpurogenum produces several xylanases: purification and properties
      of two of the enzymes.
AB  - The fungus Penicillium purpurogenum produces several extracellular xylanases. The
      two major forms (xylanases A and B) have been purified and characterized. After
      ammonium sulfate precipitation and chromatography in Bio-Gel P 100, xylanase A
      was further purified by means of DEAE-cellulose, hydroxylapatite and CM-Sephadex,
      and xylanase B by DEAE-cellulose and CM-Sephadex. Both xylanases showed apparent
      homogeneity in SDS-polyacrylamide gel electrophoresis. Xylanase A (33 kDa) has an
      isoelectric point of 8.6, while xylanase B (23 kDa) is isoelectric at pH 5.9.
      Antisera against both enzymes do not cross-react. The amino terminal sequences of
      xylanases A and B show no homology. The results obtained suggest that the enzymes
      are produced by separate genes and they may perform different functions in xylan
      degradation.

PMID- 7640005
TI  - The measurement of permeability in single rat venules using the red cell
      microperfusion technique.
AB  - The red cell microperfusion-micro-occlusion technique has been used to measure
      fluid filtration and reabsorption (Jv/A) at known microvascular pressures (Pc) in
      single mesenteric venules of anaesthetized rats. The relation between Jv/A and Pc
      is linear over the range of Pc from 15 to 50 cmH2O and its slope is the hydraulic
      permeability, Lp. Reproducible estimates of Lp can be made in the same venule in
      separate microperfusions. The value of Pc at Jv/A = 0 varies linearly with
      perfusate oncotic pressure and is the effective oncotic pressure of the
      perfusate, sigma delta pi, when the hydrostatic pressure in the pericapillary
      fluid is zero. The mean value for Lp (+/- S.E.M.) in forty venules was 2.43 (+/-
      0.2) x 10(-7) cm s-1 cmH2O-1. Two potential errors of the micro-occlusion
      technique (vessel distensibility and marker red cell size) were investigated. It
      was found that the effects of vessel distensibility had little effect on red cell
      movements at times later than 2 s after a step change in Pc. Red cell size had a
      potentially large effect on estimates of the absolute values of Lp. Cooling the
      mesenteric tissues from 37 to 7 degrees C reduced Lp in proportion to the change
      in the reciprocal of water viscosity with temperature. Rat venular permeability
      was shown to be sensitive to histamine, with Lp increasing and sigma delta pi
      falling in a concentration-dependent fashion with histamine concentrations of 1.6
      x 10(-5) to 3.3 x 10(-4) mol l-1 in the perfusate.

PMID- 7640004
TI  - Opioid tolerance and dependence in the magnocellular oxytocin system: a
      physiological mechanism?
AB  - At the neurosecretory terminals in the neural lobe, oxytocin secretion is
      restrained by co-secreted endogenous opioids, which act via kappa-receptors. The
      co-secreted opioids include products of pro-dynorphin (released by both
      vasopressin and oxytocin terminals) and proenkephalin (released by oxytocin
      terminals). In morphine-tolerant rats this opioid mechanism is more effective,
      but in late pregnancy it is less effective. Opioids also act directly on oxytocin
      cell bodies, via separate mu- and kappa-receptors, inhibiting excitation by all
      stimuli tested, and also exert presynaptic and more distal actions on afferent
      systems. During chronic morphine exposure, tolerance and dependence develop in
      oxytocin neurones; the former involves reduction in mu-opioid receptor density,
      while the latter may involve compensatory upregulation of mechanisms regulating
      Ca2+ influx. In mid-pregnancy, the effectiveness of opioid mechanisms in the
      neural lobe increases, assisting the accumulation of oxytocin stores in advance
      of parturition, but by the end of pregnancy the effectiveness of these mechanisms
      is reduced. At this time, a separate endogenous opioid system, acting via mu
      receptors, actively restrains the electrical activity of oxytocin neurones.
      Release of this endogenous opioid inhibition may contribute to the increase in
      activity during parturition analogous to that occurring during morphine
      withdrawal excitation. Central opioid mechanisms retain the ability to control
      oxytocin neurones during parturition, and can interrupt established parturition
      by inhibiting oxytocin neurone firing rate in disadvantageous environmental
      circumstances.

PMID- 7640006
TI  - Swelling-activated conductances for chloride, potassium and amino acids in the
      rat colon: a whole-cell study.
AB  - Cell swelling induced by superfusion with a hypotonic medium (152 mosmol l-1)
      induced a reversible membrane depolarization of 13.8 +/- 5.3 mV in isolated
      colonic crypts during whole-cell recording using nystatin-permeabilized patches.
      This depolarization was concomitant with an increase in Cl- current as shown by
      anion substitution. In the absence of Cl- ions, the effect of the hypotonic
      medium was reversed into a hyperpolarization, which was associated with an
      increase in membrane outward (K+) current. The hyperpolarization was dependent on
      the presence of Ca2+ ions. It was blocked by TMB-8 ((N,N-diethylamino)-octyl
      3,4,5-trimethoxy-benzoate hydrochloride; 10(-5) mol l-1), an inhibitor of
      intracellular Ca2+ release, but not by a Ca2+ channel blocker, verapamil (5 x 10(
      5) mol l-1). Using butyrate as a stimulus for cell swelling, it was investigated
      whether swelling induces a conductance for an amino acid, glutamate. In the
      absence of Cl- ions, superfusion with butyrate induced a reversible
      depolarization when glutamate was present in the intracellular medium, and a
      reversible hyperpolarization when glutamate was present in the extracellular
      medium. This response was blocked by the lipoxygenase inhibitor, NDGA
      (nordihydroguaiaretic acid, 10(-5) mol l-1), and was markedly attenuated when
      glutamate was replaced by the poorly permeable anion, gluconate. Measurements of
      the membrane current during voltage clamping revealed a modest increase in
      membrane current carried by glutamate during cell swelling. These results
      demonstrate that the dominant effect of cell swelling in rat colonic crypts is an
      increase in Cl- conductance, a smaller increase in K+ conductance and a modest
      increase in conductance of amino acids, such as glutamate.

PMID- 7640007
TI  - Influences of secretory activities in rat submandibular glands on tissue
      kallikrein circulating in the blood.
AB  - Changes in serum levels of rat tissue kallikrein (rK1) in venous blood were
      measured, using a newly developed radioimmunoassay, before and after autonomic
      nerve stimulations of submandibular salivary secretion. rK1 secreted into saliva
      under these conditions was measured by radioimmunoassay and by enzymic activity
      assay, using the fluorogenic peptide substrate D-Val-Leu-Arg-7-amino-4
      trifluoromethylcoumarin (AFC). Following an overnight fast, serum rK1
      concentration was 30-40 ng ml-1. Unilateral electrical stimulation of the
      submandibular sympathetic nerve supply (at 50 Hz in bursts of 1 s every 10 s for
      60 min) evoked a small flow of saliva with a very high rK1 concentration,
      resulting in a large output of rK1 of 2104.4 +/- 603.5 micrograms (n = 6). Such
      stimulation caused a large degranulation of granular duct cells and a
      corresponding reduction in glandular rK1 content. Unilateral electrical
      stimulation of the parasympathetic nerve supply (at 5 Hz continuously for 60 min)
      evoked a copious flow of saliva with a very low rK1 concentration, resulting in a
      low output of rK1 (18.1 +/- 4.9 micrograms; n = 6). Despite these large
      differences in salivary outputs of rK1, serum concentrations of rK1 were
      increased similarly following either sympathetic or parasympathetic stimulation
      by 48 and 46%, respectively. If the submandibular duct was briefly obstructed
      during sympathetic stimulation, inducing leakage and glandular oedema, then serum
      rK1 increased greatly (40-fold); a similar increase to that seen by others in
      previous studies without deliberate obstruction. Four days after bilateral
      submandibular-sublingual sialadenectomy serum rK1 concentration was reduced by
      approximately 50%. The results indicate that submandibular glands normally
      contribute to circulating levels of rK1 in rats, but this contribution is
      independent of the amounts of rK1 secreted into saliva by sympathetically induced
      exocytosis, and is likely to arise from basal vesicular transport. However, if
      glandular leakage occurs during sympathetic stimulation of submandibular
      secretion this then causes increases in the circulating levels of rK1 that
      correlate with the large amounts being secreted into saliva.

PMID- 7640008
TI  - Interactions between oxoglutarate oxidation and acid secretion in isolated rabbit
      gastric glands.
AB  - The effects of gastric secretagogues, and other agents that modify H+,K(+)-ATPase
      activity and cell calcium concentration, on the rate of oxoglutarate oxidation
      were investigated in isolated gastric glands. Oxoglutarate was oxidized in a dose
      dependent manner by gastric glands, with an apparent Km for oxoglutarate of 3.9
      +/- 0.5 mM. Oxoglutarate progressively inhibited the rate of glucose oxidation.
      In the presence of 0.5 mM oxoglutarate plus 10 mM glucose, the latter substrate
      was preferentially oxidized and contributed most to oxygen uptake. With 10 mM
      oxoglutarate plus 10 mM glucose, the rate of glucose oxidation was greatly
      inhibited and oxoglutarate oxidation accounted for most of the oxygen
      consumption. Acid secretion (aminopyrine accumulation) was significantly
      increased by 0.1 mM histamine in glands oxidizing 10 mM oxoglutarate, although
      this stimulation was significantly lower than that observed in the presence of
      0.5 mM oxoglutarate plus 10 mM glucose. Omeprazole, an inhibitor of the H+,K(+)
      ATPase, significantly reduced the oxidation of oxoglutarate, whereas NH4+, an
      activator of the enzyme, stimulated the oxidation of a submaximal dose of
      oxoglutarate. Carbachol at 0.1 mM significantly increased the rate of oxidation
      of non-saturating concentrations of oxoglutarate. The calcium ionophore ionomycin
      at 10 microM produced a similar effect. Chelation of intracellular calcium by
      BAPTA AM caused a significant inhibition of oxoglutarate oxidation. The results
      provide further evidence that changes in the ATP:ADP ratio resulting from
      activation of the H+,K(+)-ATPase, and calcium ions are involved in the mechanisms
      of activation of oxidative metabolism in the parietal cell.

PMID- 7640009
TI  - EB 1089, a calcitriol analogue, decreases fetal calcium content when injected
      into pregnant rats.
AB  - EB 1089 is a calcitriol analogue with low calcaemic activity, which inhibits
      parathyroid hormone-related peptide (PTHrP) secretion in rats implanted with the
      Leydig cell tumour H-500. We have studied its effect on maternal and fetal plasma
      PTHrP concentrations and on fetal calcium and phosphorus contents in rats. Three
      groups of six pregnant rats were injected I.P. daily with EB 1089 (0.10, 0.25 and
      0.50 microgram kg-1 in groups 1, 2 and 3, respectively, from day 12 to day 20 of
      gestation). The control group received an equal volume of solvent alone. On day
      21 of gestation the animals were anaesthetized with chloral hydrate and blood
      samples were taken. Fetuses were collected, weighed and ashed for Ca and P
      measurements. PTHrP concentrations were measured by radioimmunoassay (RIA) in
      maternal and fetal plasma. Calcium content (mg (g fetal wt)-1; mean +/- S.E.M.)
      in control fetuses was not different from that measured in fetuses from dams
      given the lowest dose of EB 1089, but was higher than that in fetuses from rats
      injected with EB 1089 at 0.25 microgram kg-1 (1.18 +/- 0.20; P < 0.05) or 0.50
      microgram kg-1 (1.08 +/- 0.29; P < 0.05). There was no difference in fetal P
      content between any of the groups of rats. The PTHrP concentration (pg
      equivalents human PTHrP(1-34) fragment ml-1) in maternal plasma from control rats
      (1.70 +/- 0.50) was not different from that in maternal plasma of rats given the
      lowest dose of EB 1089 (1.44 +/- 0.63).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7640010
TI  - The glucogenic capacity of the fetal pig: developmental regulation by cortisol.
AB  - In the present study, the ontogenic changes in gluconeogenic enzyme activities
      and in hepatic glycogen and beta-adrenergic receptor levels were investigated in
      fetal pigs from 70 days of gestation until delivery at term (114 +/- 2 days). The
      values were compared with those observed in fetuses infused subcutaneously with
      cortisol for 6 days beginning at 82-84 or 92-94 days of gestation. Tissue glucose
      6-phosphatase (G6Pase) activity increased with increasing gestational age in the
      liver, kidney and duodenum of control fetal pigs. At birth, there was a further
      increase in G6Pase activity in the liver but not in the kidney or duodenum. In
      the kidney, there was a similar gestational increase in phosphoenolpyruvate
      carboxykinase (PEPCK) activity. These changes in enzyme activities closely
      paralleled the prepartum increase in fetal plasma cortisol and were accompanied
      by increases in hepatic glycogen content and beta-adrenergic receptor density. At
      98-100 days, there were significant increases in G6Pase activity in the liver,
      kidney and duodenum of the cortisol-infused fetuses, whereas at 88-90 days only
      renal G6Pase was significantly elevated by cortisol infusion. Cortisol infusion
      also increased hepatic beta-receptor density at 88-90 days and hepatic glycogen
      content at both gestational ages. There were no changes in hepatic PEPCK, hepatic
      or renal fructose diphosphatase and aspartate amino transferase activities during
      cortisol infusion or with increasing gestational age. When the data from all the
      piglets were combined, irrespective of age or treatment, there were significant
      positive correlations between log plasma cortisol and G6Pase activity in the
      liver, kidney and duodenum. Similar positive correlations were observed between
      hepatic beta-adrenoceptor density and log plasma cortisol and between the latter
      values and the hepatic glycogen content. These findings show that cortisol
      induces tissue G6Pase activity in the fetal pig and suggest that the prepartum
      rise in endogenous cortisol may be responsible for the increase in fetal
      glucogenic capacity observed towards term in this as in other species.

PMID- 7640012
TI  - Force responses to controlled stretches of electrically stimulated human muscle
      tendon complex.
AB  - Human first dorsal interosseus muscle was tetanized using percutaneous electrical
      stimulation. During the tetanus the muscle was subjected to constant velocity
      stretches. The stretch produced an enhancement of muscular force of up to 80%
      during the stretch. The size of the enhancement was dependent on both the
      amplitude and the velocity of the stretch. During an isometric hold phase after
      the stretch, the force decayed quickly for the first 100 ms and thereafter much
      more slowly, reaching a level 30% higher than the isometric force without pre
      stretch. The force during this hold phase was dependent on amplitude of stretch
      but was independent of stretch velocity. The interaction of tendon elasticity and
      muscle fibre mechanics in producing these responses is discussed. Implications
      for normal human movements are also explored.

PMID- 7640011
TI  - Effect of oral corticosterone administration on locomotor development of neonatal
      and juvenile rats.
AB  - In order to simulate the elevated corticosteroid levels to which offspring of
      stressed women may be subjected, rat pups were treated daily with two levels of
      oral corticosterone from the 2nd to the 15th postnatal day. The rat pups were
      subjected to swimming tests from their 8th postnatal day to examine their
      neuromuscular development and learning abilities. The locomotor performance of
      corticosterone-treated groups was similar to that of controls but its development
      was delayed, which demonstrates that even relatively low levels of corticosterone
      have a significant negative influence on the maturation and learning ability of
      neonatal rat pups. This indicates that the glucocorticoid levels to which
      suckling neonates (for example, children of women suffering from stress) might be
      exposed could modify the complex integrated neuromuscular adaptive mechanisms
      involved in normal locomotor development.

PMID- 7640013
TI  - The effects of MM-creatine kinase deficiency on sustained force production of
      mouse fast skeletal muscle.
AB  - Twitch force production was normal in muscles of mice which lack MM-creatine
      kinase, but the tetanic force:twitch force ratio was lower than in control
      muscles (3.60 vs 4.27; P < 0.05). In a series of repeated tetanic contractions
      the force in the second contraction was already markedly depressed (20-50%),
      while subsequently only small changes were observed. The effect was greater in
      exercise that would require a higher metabolic peak flux. The depressed force
      production was not accompanied by a slowing of relaxation, indicating that enough
      ATP was present to sustain myofibrillar ATPase and Ca(2+)-ATPase activity.

PMID- 7640014
TI  - Reference values for normal adult transesophageal echocardiographic measurements.
AB  - Normal transesophageal echocardiographic measurements have not been presented
      previously relative to the effects of age, sex, and body surface area. This
      comparison was obtained by measuring cardiac and aortic dimensions in 60 patients
      (20 to 75 years old; 33 women) with normal transesophageal echocardiograms. We
      found a variable and usually important relationship between body surface area and
      11 of 20 structures measured. A gender effect was not significant after indexing
      for body surface area for all but one structure. Age correlated with the diameter
      of the aortic root, descending aorta, superior vena cava, and right pulmonary
      artery. Similar dimensions were noted for certain paired structures as the two
      atria, the mitral and tricuspid annuli, and the aortic root and right ventricular
      outflow tract. Although multiple factors underlie what is normal in a given
      individual, our reference values serve to facilitate recognition of cardiac and
      aortic disease.

PMID- 7640015
TI  - Transesophageal transgastric echocardiography in infants and children: the
      subcostal view equivalent.
AB  - Transesophageal echocardiography has been limited in the assessment of congenital
      heart disease involving ventriculoarterial connections. These can be viewed with
      biplane imaging, but the angle of incidence does not permit assessment of
      gradients. To determine whether transgastric transesophageal imaging could
      provide this information, we examined 127 infants and children during cardiac
      surgery, ranging from 2.7 to 32 kg in weight and 1 day to 16 years in age. The
      additional information (if any) provided by the transgastric plane, the frequency
      with which views could be obtained, the value in examining different congenital
      heart lesions, and assessing reductions in pressure across the left and right
      ventricular outflow tracts were determined. Slices obtained from anatomic
      specimens substantiated the imaging planes and confirmed the anatomic features.
      Transgastric images were obtained successfully in 89% of patients. Doppler
      estimates of pressure drops across the ventricular outflow tracts were within
      good limits of agreement with estimates obtained by manometry. There were no
      major complications from this technique. We conclude that the transgastric
      viewing plane enhances the usefulness of intraoperative transesophageal
      echocardiography for diagnosis and evaluation of congenital heart lesions by
      permitting more complete echocardiographic examinations and detection of areas of
      residual obstruction across the ventricular outflow tracts.

PMID- 7640016
TI  - The utility of transesophageal echocardiography in the management of renal cell
      carcinoma with intracardiac extension.
AB  - The accurate assessment of the distal extent of vena caval invasion of renal cell
      carcinoma into the hepatic veins, inferior vena cava, and right atrium is
      critical before surgical resection. We present two cases of renal carcinoma with
      vena caval extension in which preoperative transesophageal echocardiography
      accurately assessed tumor extent and guided surgical therapy. The role of
      transesophageal echocardiography in comparison to other diagnostic modalities is
      discussed.

PMID- 7640017
TI  - Transesophageal echocardiographic demonstration of resolution of mitral
      vegetations after warfarin in a patient with the primary antiphospholipid
      syndrome.
AB  - A 16-year-old girl with multiple cerebral infarcts was reported to have a normal
      transthoracic echocardiogram, but transesophageal echocardiography revealed
      vegetations on the atrial surfaces of both mitral leaflets at their line of
      closure. Blood cultures were negative, and prolonged treatment with intravenous
      antibiotics produced no echocardiographic improvement in the appearance of the
      vegetations. A diagnosis of primary antiphospholipid syndrome was made
      subsequently, although test results for this condition had initially been normal.
      Serial transesophageal echocardiograms showed complete resolution of the
      vegetations but some persistent thickening of the mitral leaflets, after warfarin
      therapy for 9 months. We suggest that in patients with culture-negative
      endocardial vegetations, specific tests should be performed for the primary
      antiphospholipid syndrome and a therapeutic trial of warfarin should be
      undertaken before contemplating heart surgery.

PMID- 7640018
TI  - "Views from the back" by subscapular retrocardiac imaging: technique and clinical
      application.

PMID- 7640020
TI  - Intraventricular early diastolic velocity profile during acute myocardial
      ischemia: a color M-mode Doppler echocardiographic study.
AB  - The aim of the study was to investigate the effect of acute myocardial ischemia
      on the early diastolic mitral-to-apical velocity profile. Intraventricular
      filling velocities were measured by color M-mode Doppler echocardiography, which
      allows simultaneous measurements of velocities at multiple sites. Twenty patients
      were examined during angioplasty and eight dogs during transient coronary artery
      occlusion. Velocities at each 0.46 cm level from the mitral tip toward the apex
      were determined at the time of peak early transmitral velocity. Before
      angioplasty, early diastolic flow velocities decreased progressively from the
      mitral tip toward the apex. During angioplasty, intraventricular velocities
      showed a more abrupt decrease from the middle region toward the apex (p < 0.05).
      A similar change in the mitral-to-apical profile was found during myocardial
      ischemia in dogs (p < 0.05). Also, there was a decrease in peak early transmitral
      velocity (p < 0.01) and peak early transmitral pressure gradient (p = 0.06).
      Volume loading and constriction of the caval veins performed in the nonischemic
      ventricle did not appear to change the mitral-to-apical velocity profile.
      Regional myocardial ischemia was associated with a change in the mitral-to-apical
      velocity profile as measured by color M-mode Doppler echocardiography. The
      altered filling pattern could not be explained by changes in loading conditions
      and may reflect impaired relaxation of the ischemic ventricle.

PMID- 7640019
TI  - The spectrum of left ventricular-right atrial communications in the adult:
      essentials of echocardiographic assessment.
AB  - Left ventricular-right atrial communication may be a congenital defect or can
      result from trauma, endocarditis, or valve replacement. Traditionally the
      preoperative diagnosis of this entity was made during cardiac catheterization,
      but recent advances in echocardiography, particularly color Doppler imaging, have
      greatly facilitated the noninvasive diagnosis of left ventricular-right atrial
      communication. We present four cases of left ventricular-right atrial
      communication, each identified by two-dimensional and color Doppler imaging. One
      case is a congenital defect, two were identified years after cardiac surgery, and
      one presents as an unusual complication of myocardial infarction. Optimal views
      for identifying this defect are discussed along with clues to quantifying its
      hemodynamic significance.

PMID- 7640021
TI  - The value of two-dimensional echocardiography and Doppler examination in the
      assessment of hypertensive patients: a pilot study.
AB  - There has been hesitation in accepting the routine use of echocardiography in
      patients with hypertension. The concept of "limited" or "focused"
      echocardiography has been introduced but incompletely evaluated. In this
      prospective observational cohort study, 100 consecutive hypertensive adults
      underwent comprehensive two-dimensional echocardiography and Doppler assessment
      regardless of referral question. Patients were categorized on the basis of
      echocardiographic referral questions into two groups: (1) determination of left
      ventricular mass only (limited echocardiography) and (2) determination of left
      ventricular mass and associated cardiac problems. In group 1, missed diagnoses
      were rare (5%). Additional, clinically relevant information was provided by
      comprehensive echocardiography in 9% of patients. Doppler echocardiography did
      not provide any additional useful information in group 1 but was useful in group
      2. In both groups, echocardiography affected clinical management. In patients
      referred for determination of left ventricular mass only, the equivalent of
      limited echocardiography, missed diagnoses are rare. Additional, clinically
      relevant information is provided in only a small number of patients by
      comprehensive two-dimensional echocardiography. Comprehensive two-dimensional
      echocardiography, including Doppler echocardiography, was useful in selected
      patients referred with hypertension and other cardiac problems and should be part
      of the echocardiographic assessment of such patients. With careful selection of
      hypertensive patients, limited echocardiography can be a cost-effective strategy.

PMID- 7640022
TI  - Pulsatile pressure affects the disappearance of echocardiographic contrast
      agents.
AB  - The purpose of this study was to determine in an in vitro model the effect of
      pulsatile pressure on the decay of echocardiographic contrast agents. Use of
      contrast agents for quantitative assessment of perfusion requires understanding
      of the factors controlling their rates of disappearance. Prior studies have shown
      that constant pressure affects the rate of disappearance of these agents. It is
      not known whether pulsatile pressure influences the rate of decay of contrast
      agents. In an in vitro chamber, three contrast agents (Albunex, hand-agitated
      saline solution, and hand-agitated Angiovist) were exposed to pulses of pressure
      at three rates (30, 60, and 120 pulsations/min), keeping pressure characteristics
      (peak, nadir, and mean) within a narrow range. Five injections were performed for
      each agent at each rate. Two-dimensional echocardiographic images of the effects
      of contrast material were recorded from injection until total disappearance.
      Videointensity was measured and time-intensity curves were generated. These
      curves of intensity decay were fitted to an exponential decay function (I = Ae
      lambda t) and the velocity of decay (lambda) was used for comparisons. For all
      agents, intensity of contrast decreased over time. Saline solution and Angiovist,
      but not Albunex, showed pulsatile decreases in intensity of contrast with each
      peak pressure and partial recovery of contrast intensity with each nadir
      pressure. (ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7640023
TI  - Technical guidelines for performing automated border detection studies.

PMID- 7640024
TI  - JPEG compression of digital echocardiographic images: impact on image quality.
AB  - Routine echocardiograms are not handled digitally because of enormous storage
      needs. Image compression techniques can reduce memory requirements, but the
      impact on diagnostic content is unknown. We studied the effect of an
      internationally accepted compression algorithm called Joint Photographic Experts
      Group (JPEG) on digital echocardiographic images. Diagnostic and image quality of
      JPEG compressed, two-dimensional echocardiograms at ratios ranging from 4:1 to
      40:1 was compared with that of uncompressed images both subjectively by a blinded
      expert panel (540 observations) and objectively by quantitative image-processing
      parameters (180 images). Accuracy of 432 measurements performed on compressed M
      mode and spectral Doppler tracings was determined. Simultaneously acquired
      videotaped images and their never-compressed digital counterparts were compared
      quantitatively for image fidelity. This study demonstrates that the JPEG
      compression algorithm produces little degradation of echocardiographic images at
      compression ratios of at least 20:1, with less measured distortion than is
      produced by videotape recording. With JPEG, digital storage and retrieval in
      routine echocardiography are feasible.

PMID- 7640025
TI  - The DICOM Image Formatting Standard: what it means for echocardiographers.

PMID- 7640026
TI  - Inverted left atrial appendage presenting as an unusual left atrial mass.
AB  - An unusual left atrial mass in an infant after repair of truncus arteriosus was
      imaged by transthoracic and transesophageal echocardiography. The mass was
      identified as an inverted left atrial appendage, and the patient underwent
      uncomplicated surgical eversion. Unnecessary anticoagulation was avoided.

PMID- 7640027
TI  - A case report of complete heart block caused by non-Hodgkin's lymphoma: the
      diagnostic role of transesophageal echocardiography.
AB  - We present a very rare case of complete atrioventricular block caused by
      malignant lymphoma diagnosed before death by transesophageal echocardiography. We
      believe that early detection of metastatic cardiac involvement of tumor is
      important for proper diagnostic and therapeutic interventions.

PMID- 7640028
TI  - Myocardial abscess complicating myocardial infarction.
AB  - Myocardial abscess may occur rarely as a complication of myocardial infarction.
      This case report is the first demonstration of a myocardial abscess at the site
      of acute myocardial infarction in a 38-year-old man diagnosed by transesophageal
      echocardiography and color-flow imaging. Transesophageal echocardiography was
      crucial in the timing of surgery. Three months later the patient was well. Our
      patient is the first reported survivor of this uncommon complication of
      myocardial infarction.

PMID- 7640029
TI  - Saphenous vein graft pseudoaneurysm: diagnosis by transesophageal
      echocardiography and magnetic resonance imaging.
AB  - Coronary cineangiography showed probable pseudoaneurysm formation at the origin
      of an 11-year-old saphenous vein coronary bypass graft. Transesophageal
      echocardiography and magnetic resonance imaging were helpful in differentiating
      this from aortic dissection or true aneurysm formation and assisted the surgeon
      in avoiding perforation of the pseudoaneurysm during sternotomy.

PMID- 7640030
TI  - Decision making in abdominal surgery following chemotherapy for testicular
      cancer.

PMID- 7640031
TI  - Ovarian cancer: diagnostic second laparotomy and salvage intra-peritoneal
      chemotherapy fail again.

PMID- 7640032
TI  - Childhood cancer: trends in incidence, survival and mortality.

PMID- 7640033
TI  - Is there a need to follow-up cancer patients?

PMID- 7640034
TI  - Differences in the growth pattern and clinical course of EBV-LMP1 expressing and
      non-expressing nasopharyngeal carcinomas.
AB  - All low differentiated or anaplastic forms of nasopharyngeal carcinoma (NPC)
      carry multiple copies of EBV-DNA and express EBNA1. The major membrane protein,
      LMP1, is only expressed in 65% of the tumours. The physiological function of LMP1
      in the viral life cycle is unknown, but it has been shown to transform
      established rodent fibroblasts and immortalised human keratinocytes in vitro, and
      to increase the likelihood of a malignant transformation. We studied 74 cases
      collected from the Shanghai and Guanzhou areas in China. LMP1 expression was
      assessed in tumour biopsies by immunoblotting. Clinical and follow-up data were
      evaluated according to the classification of WHO. The laboratory and the clinical
      data were assembled in a mutually independent double blind fashion. Our findings
      indicate that the LMP1-positive tumours grew faster and more expansively than
      LMP1-negative tumours, but nevertheless had a better prognosis. LMP1-negative
      tumours recurred at a higher frequency, and showed an increased tendency to
      metastasise.

PMID- 7640035
TI  - Prognostic value of total cathepsin B in invasive ductal carcinoma of the breast.
AB  - Total cathepsin B (catB) was determined by ELISA in 62 specimens of invasive
      ductal carcinoma of the breast. It was measured in microgram/g of tumour protein
      (microgram/gtp). The median catB was 91 micrograms/gtp, not varying significantly
      with T-stage or with age. It was higher in lymph-node negative (143
      micrograms/gtp) than in lymph-node positive patients (49 micrograms/gtp) (P =
      0.0005), in grade 3 (132 micrograms/gtp) than in grade 1 and 2 tumours (72
      micrograms/gtp) (P = 0.07) and in hormone receptor-negative (155 micrograms/gtp)
      than in hormone receptor-positive tumours (72 micrograms/gtp) (P = 0.025). The
      recurrence-free survival (RFS) at 54 months for patients with tumours with catB <
      or = 23 micrograms/gtp was 22% and for catB > 23 micrograms/gtp, 68% (P =
      0.0004). CatB > 23 micrograms/gtp did not significantly influence the RFS.
      Multivariate analysis showed that lymph nodes involvement (P = 0.003) and catB (P
      = 0.007) were independent prognostic factors.

PMID- 7640036
TI  - Feasibility of five courses of pre-operative chemotherapy in patients with
      resectable adenocarcinoma of the oesophagus or gastrooesophageal junction.
AB  - The purpose of this study was to examine the feasibility of administering all
      chemotherapy pre-operatively to patients with resectable adenocarcinoma of the
      oesophagus or gastrooesophageal junction. 32 patients with potentially resectable
      adenocarcinoma of the oesophagus or gastrooesophageal junction were studied in a
      stepwise fashion in which combination chemotherapy with cisplatin, high-dose
      arabinoside and 5-fluorouracil was administered. In the first part, 15 patients
      were to receive three chemotherapy courses pre-operatively and two chemotherapy
      courses postoperatively. In the second part, the next 15 patients were to receive
      all five chemotherapy courses pre-operatively, provided there was an objective
      response after three courses. Endoscopic ultrasonography was also performed, when
      feasible, prior to chemotherapy and surgery, and in some patients sequentially
      between chemotherapy courses. All of the 14 assessable patients in the first
      group tolerated all three courses of pre-operative chemotherapy, and 86% of
      patients in this group completed all protocol chemotherapy. In the second group,
      9 of 18 (50%) assessable patients tolerated all five courses of preoperative
      chemotherapy, and 100% of patients in this group received all protocol
      chemotherapy. The median number of chemotherapy courses for the entire group (32
      patients) was five (range one to five). Forty-one per cent (13/32) of patients
      had a major response to chemotherapy. Sixty-nine per cent (or 76% of 29 patients
      taken to surgery) had a curative resection. One patient had a pathological
      complete response. The median survival time of 32 patients was 17 months (range 2
      36+ months). 14 patients (37%) remain alive at a median follow-up time of 26+
      months. There was a correlation between endoscopic ultrasonographic tumour and
      nodal stage and pathological tumour and nodal stages in 16 patients. The tumour
      stage correlation was higher (75%) than the nodal stage correlation (62%). Our
      data suggest that it is feasible to administer five courses of cisplatin-based
      chemotherapy to patients with potentially resectable adenocarcinoma of the
      oesophagus or gastrooesophageal junction. More effective chemotherapy regimens
      that might result in higher pathological complete response rates and acceptable
      toxic effects are needed.

PMID- 7640037
TI  - Relationship between cathepsin D and other pathological and biological parameters
      in 1752 patients with primary breast cancer.
AB  - The relationship between cathepsin D and other pathological or biological
      prognostic parameters has not yet been defined through systematic studies in
      breast cancer. The aim of the present investigation was to define the
      relationship between cathepsin D and nodal status, tumour size, steroid receptors
      and tumour grade in a wide patient series. Cytosol cathepsin D was assayed with
      an immunoradiometric assay in tumour samples from 1752 patients. A statistically
      significant, but not biologically meaningful association was found between
      cathepsin D and both tumour size and grade. Cathepsin D was significantly higher
      in node-positive than in node-negative tumours. However, cathepsin D is not of
      great use in order to predict the risk of axillary metastases in individual
      patients, due to overlapping of cathepsin D values between node-positive and node
      negative cases. A significant, direct association was found between cathepsin D
      and both oestrogen receptor and progesterone receptor cytosol levels.
      Nevertheless, preliminary data indicate that cathepsin D and steroid receptors
      provide independent prognostic information.

PMID- 7640038
TI  - Neurotoxicity is not enhanced by increased dose intensities of cisplatin
      administration.
AB  - It is uncertain whether intensive dosing schedules of cisplatin, intended to
      attain a higher anti-tumour efficacy, alter the severity of cisplatin-induced
      neuropathy. We assessed the development of neuropathy in three groups of patients
      treated with cisplatin in different dosing schedules. The severity of neuropathy
      was determined by measurement of the vibration perception threshold (VPT) before
      treatment and during follow-up for 2-12 months after the last cycle. 66 patients
      were treated with an intensive weekly regimen of doses varying from 70 to 85
      mg/m2 in 1 day (trial A), 21 patients with a 3-weekly combination chemotherapy
      containing cisplatin 75 mg/m2 in 1 day (trial B) and 20 patients with a 3-weekly
      regimen containing cisplatin 20 mg/m2 for 5 consecutive days (trial C). The mean
      dose intensity achieved was 59 mg/m2/week in trial A, 21 mg/m2/week in trial B
      and 33 mg/m2/week in trial C. The maximum post-treatment VPT correlated
      significantly with pretreatment VPT (P < 0.001) and with the cumulative dose of
      cisplatin (P < 0.001). Following correction for these two variables, the maximum
      posttreatment VPT did not show a statistically significant association with dose
      intensity. These results suggest that neuropathy is not related to dose intensity
      of cisplatin. This implies that treatment with more intensive dosing schedules,
      employing equal cumulative doses of cisplatin, does not result in a concomitant
      increase in neurotoxicity within a cumulative dose range of 280-675 mg/m2.

PMID- 7640039
TI  - Single-dose intraperitoneal radioimmunotherapy with the murine monoclonal
      antibody I-131 MOv18: clinical results in patients with minimal residual disease
      of ovarian cancer.
AB  - Sixteen of 19 enrolled patients with minimal residual disease of ovarian cancer
      (macroscopic disease < 5 mm or positive blind biopsies and/or positive peritoneal
      washing), demonstrated by surgical second-look, underwent intraperitoneal
      radioimmunotherapy (RIT) with the radiolabelled monoclonal antibody I-131 MOv18
      (mean dose 14 mg of MOv18 with 3700 GBq of I-131) 30-40 days after the second
      look procedure. Clinical follow-up and/or third-look evaluation performed 90 days
      after RIT showed complete response (CR) in 5 patients, no change (NC) in 6
      patients and progressive disease (PD) in 5 patients. Follow-up study showed long
      term maintained CR in 1 patient (34 months) and relapses in the other 4 patients
      after a mean disease-free period of 10.5 months. 5 NC patients showed clinical or
      instrumental progression after a mean disease-free period of 13 months. The
      toxicity of RIT was negligible. Only 1 patient showed mild and transient bone
      marrow suppression (platelet count nadir 52,000 mm3 after 30 days). HAMA
      production was demonstrated in 94% (15/16) of patients. In conclusion, RIT
      appears to be a very promising therapeutic approach to treat minimal residual
      disease of ovarian cancer.

PMID- 7640040
TI  - Prognostic factors for survival after breast conserving therapy for stage I and
      II breast cancer. The role of local recurrence.
AB  - Risk factors for local recurrence (LR) in a univariate analysis had a significant
      correlation with survival. Local and distant failure could not be regarded as
      independent events. We undertook a multivariate survival analysis to study the
      relation between LR and survival. In a retrospective study of 1026 patients
      treated with tumorectomy, axillary dissection and radiotherapy, factors
      associated with disease-specific survival (DSS) were analysed. Actuarial
      estimates for DSS are 91% at 5 years and 86% at 10 years. The multivariate
      analysis revealed five factors: clinical stage, number of affected axillary
      nodes, histological grade, degree of tubule formation and left-sided primary
      tumour. Controlling for these factors, LR appeared to be significantly correlated
      with DSS. The hazard rate of DSS was estimated to increase by a factor 8.8 (95%
      confidence interval 4.6-16.8) upon occurrence of a LR. Local recurrence per se,
      apart from the identified prognostic factors, is a risk factor for DSS. The exact
      mechanism by which LR has an influence on survival cannot be clarified from these
      data.

PMID- 7640041
TI  - Adoptive transfer of ex vivo activated memory T-cells with or without
      cyclophosphamide for advanced metastatic melanoma: results in 36 patients.
AB  - Autolymphocyte therapy (ALT) is the infusion of autologous peripheral blood
      mononuclear cells (PBMC) activated ex vivo by a cytokine-rich supernatant (T3CS)
      generated from a previous autologous lymphocyte culture using low doses of the
      anti-CD3 mitogenic monoclonal antibody. The mechanism of action is enhancement of
      a recall response by CD45RO+ (memory) T-cells (ALT cells) to host tumour without
      dependence on exogenous interleukin (IL)-2. The existence of anti-tumour-specific
      T-cells in melanoma patients has been well described, and efforts to utilise them
      therapeutically have achieved modest tumour response rates. However, few long
      term survival data have been reported. From 1986 to 1992, we treated 36 patients
      with disseminated melanoma using ALT alone (26 patients) or adoptive
      chemoimmunotherapy using ALT and cyclophosphamide (CY) (10 patients). Over this
      time period, the cell activation method evolved from using cytokine supernatants
      derived from a one-way allogeneic mixed lymphocyte culture (MLCS), to the current
      practice of utilising anti-CD3 and autologous cytokines (T3CS). There were 21 men
      and 15 women, average age 57 years, range 30-82. 27 had failed prior therapies
      and 9 had no prior therapy. A total of 161 infusion of ALT cells were given: 65
      with cells activated in MLCS and 96 with T3CS. There were no grade 3 adverse
      events, and an approximate 20% incidence of grades 1 and 2 reactions to ALT-cell
      infusions. Transient cytopenias were seen in patients receiving CY. Sixty-one per
      cent (22/36) of patients received the planned six ALT-cell infusions, while 39%
      did not due to progressive disease. In 33 evaluable patients, there were four
      complete responses, four partial responses and 6 patients with stable disease
      (SD). Responding patients and those with SD had prolonged survival compared to
      historical controls when matched for number of organ systems involved. Ex vivo
      depletion of CD45RO+ T-cells revealed preferential lysis of autologous and HLA-A
      matched melanoma targets that was dependent on these memory T-cells. These data
      suggest that adoptive cellular therapy using ex vivo activated memory T-cells
      with and without CY is active, has low toxicity, is tumour-specific and can
      result in clinical benefit in patients with disseminated melanoma.

PMID- 7640042
TI  - Phase II study of intraperitoneal cisplatin plus systemic etoposide as second
      line treatment in patients with small volume residual ovarian cancer.
AB  - The efficacy and toxicity of intraperitoneal (i.p.) cisplatin plus systemic
      etoposide were studied in 36 patients with small (< 2 cm) residual i.p. ovarian
      cancer after achieving a partial response to platinum-based, first-line
      chemotherapy. Treatment comprised 90 mg/m2 i.p. cisplatin with intravenous (i.v.)
      sodium thiosulphate (day 1) and 600-800 mg/m2 i.v. etoposide (days 1 and 2),
      every 4 weeks for four to six cycles. 7 patients achieved a pathological complete
      response (pCR), one a pathological partial response and 16 were clinically stable
      without evidence of disease. After a median follow-up of 13 months, the median
      progression-free survival (PFS) was 11 months (95% confidence interval 7-16
      months). The actuarial PFS at 24 months is 22% (95% confidence interval 8-36%).
      Three of six relapses after achieving a pCR (50%) were sited i.p., and 9 of 14
      other patients with disease progression (64%) had an i.p. relapse, indicating
      insufficient local efficacy. There was no renal toxicity, but grade 3-4
      leucopenia occurred in 63% and grade 3-4 thrombocytopenia in 8% of cycles, while
      nausea, vomiting and complete alopecia were common. Although side-effects were
      acceptable, the efficacy of treatment with i.p. cisplatin plus i.v. etoposide is
      limited.

PMID- 7640043
TI  - The effects of oral pentoxifylline on interleukin-2 toxicity in patients with
      metastatic renal cell carcinoma.
AB  - Interleukin-2 (IL-2) mediates the regression of metastatic renal cell carcinoma,
      but clinical application has been limited by associated toxicities. Preclinical
      studies show that pentoxifylline (PTXF), a methylxanthine derivative, inhibits IL
      2 toxicity while preserving anti-tumour efficacy. This study was designed to
      determine whether oral PTXF would alter IL-2-induced toxicities. Patients with
      disseminated renal cell carcinoma were treated with continuous infusion of 18 x
      10(6) IU/m2/24 h for 4 days followed by 3 days without treatment, for 4
      consecutive weeks. After a 2-week interval, the 4-week treatment cycle was
      repeated. All patients concomitantly received oral PTXF (2000 mg/24 h) in five
      divided doses. Despite the co-administration of PTXF, all patients demonstrated a
      spectrum and severity of toxicities consistent with previous reports of
      continuous infusion of IL-2 alone. There was considerably more nausea and
      vomiting associated with the administration of PTXF which improved on withdrawal
      of PTXF. Oral PTXF in IL-2 therapy did not show any substantiated benefit.
      Indeed, patients suffered more severe nausea and vomiting than if they had
      received IL-2 alone, resulting in the early termination of the trial.

PMID- 7640045
TI  - A case-control study on breast cancer and body mass. The American Health
      Foundation--Division of Epidemiology.
AB  - A hospital-based case-control study was carried out to examine the effect of body
      weight/fat and physical activity on risk of breast cancer on 617 newly diagnosed
      breast cancer cases and 531 controls matched to the cases by age (+/- 5 years),
      race, year of interview (+/- 1 year) and hospital of admission. Breast cancer was
      not found to be associated with height, while being overweight appeared to be
      protective in premenopausal women [odds ratio, OR = 0.4 (0.2-0.7) for cases who
      weighted > or = 72.7 kg versus controls]. Increased body mass index (BMI) was
      protective in premenopausal women [OR = 0.4 (0.2-0.6) in breast cancer cases with
      BMI > or = 27 versus controls], but not in postmenopausal women, for whom it was
      a risk factor [OR = 1.5 (1.0-2.3)]. Few women reported any strenuous physical
      activity from ages 15 to 22 years (22% of premenopausal, 13% of postmenopausal
      women), and no significant effect on breast cancer risk was observed.

PMID- 7640044
TI  - High-dose carboplatin and etoposide for salvage chemotherapy of germ cell
      tumours.
AB  - We evaluated high-dose carboplatin and etoposide with autologous bone marrow stem
      cell support in the salvage treatment of patients with metastatic germ cell
      tumours who had failed previous chemotherapy. The treatment programme comprised
      initial conventional dose chemotherapy. 23 patients received a first cycle of
      high-dose treatment, and 12 who showed no evidence of progression had a second
      cycle 2-3 months later. 8 of the 23 patients treated with high-dose chemotherapy
      are alive in remission 4-29 months from the start of high-dose treatment. 3 of
      these 8 required further treatment for recurrence. In the initial part of the
      study, the dose of carboplatin was escalated in successive patients. Grade 3/4
      treatment-related toxicity occurred in 4 of 18 patients (1 fatal) who received
      carboplatin doses to give a AUC (area under the serum concentration/time curve)
      of 30 mg.min/ml or less and 3 of 5 patients (2 fatal) who received higher doses.
      We, therefore, recommend 30 mg.min/ml for further evaluation in chemotherapy
      sensitive patients.

PMID- 7640046
TI  - Quality assurance in cervical cancer screening: the Icelandic experience 1964
      1993.
AB  - Monitoring of the effectiveness of a screening programme is vital to ensure
      optimal use of public resources. This report correlates the results of the
      Icelandic cervical cancer screening programme with the results of monitoring the
      programme since 1964. Screening has significantly decreased both the incidence
      and mortality rates and greatly affected the stage distribution of squamous cell
      carcinomas, but not of adeno- and adenosquamous carcinomas. In the 25-64 years
      age group, 84% were screened, 80% of whom were in the organised screening. Smears
      taken outside the guidelines amounted to 10%. Sensitivity at 1 year was 93% for
      all smears. At 3 years it was 81% for squamous cell carcinomas, and 42% for adeno
      and adenosquamous carcinomas. The rate of unsatisfactory smears was 1.3% for all
      smears, and 4.5% of the women had abnormal smears (7.7% in the 20-24 years age
      group). The specificity of the smears test was 98%. It is concluded that
      monitoring is vital for optimal screening results and although screening is
      effective in the targeted age group of 25-64 years it should preferably start
      sooner after age 20 years with a screening interval of 2-3 years.

PMID- 7640047
TI  - Detection of TP53 gene mutations in human sarcomas.
AB  - To determine the frequency and type of TP53 mutations in human sarcomas, we
      examined exons 5-8 of the TP53 gene in 48 sarcomas using single-strand
      conformation polymorphism (SSCP) analysis and direct sequencing. Nine tumours had
      mobility-shifts on SSCP analysis, and sequencing of six of these tumours revealed
      10 mutations: one insertion, two deletions and seven point mutations (four
      transitions and three transversions). Four of these mutations resulted in frame
      shifts, one in a truncated protein, four cases in mono-allelic point mutations
      and one case in an altered splice site. These data show that approximately 20% of
      sarcomas harbour TP53 gene alterations and illustrate a variety of TP53 gene
      mutation types.

PMID- 7640048
TI  - Programmed cell death in response to chemotherapeutic agents in human germ cell
      tumour lines.
AB  - Testicular germ cell tumours are amongst the most chemosensitive neoplasms both
      in vivo and in vitro. In the present study we demonstrate that following exposure
      to drugs used in chemotherapeutic treatment of testicular germ cell cancer tumour
      cells undergo death by apoptosis. Thus, after exposure of the GCT27 embryonal
      carcinoma cell line to cisplatin, we observed the degradation of DNA into
      oligonucleosomal fragments, which is a hallmark of apoptosis. Furthermore, light,
      fluorescence and electron microscopy reveal the presence of condensed abnormal
      shaped nuclear chromatin which is characteristic of apoptosis. Changes diagnostic
      of apoptosis were also observed following (a) cisplatin treatment of the GCT48
      and Susa embryonal carcinoma cell lines and the GCT44 yolk sac tumour cell line
      and (b) etoposide treatment of the GCT27 and Susa cell lines. When the GCT27 cell
      line was treated with 15 microns cisplatin, apoptosis was first observed at 6-9 h
      and greater than 90% of cells were dead within 24 h. Apoptosis was not blocked
      when cisplatin-treated cells were incubated in the presence of cycloheximide,
      although this agent did cause a 4-6 h delay in the onset of cell death. In
      addition, we demonstrated that the GCT27 cell line can be induced to undergo
      apoptosis by exposure to low concentrations of the calcium ionophore, ionomycin.
      These observations show that germ cell tumours are remarkably sensitive to a
      range of agents that act by different mechanisms. They are triggered to undergo
      apoptosis rapidly by a mechanism that is not blocked by inhibitors of protein
      synthesis.

PMID- 7640049
TI  - Temozolomide reduces the metastatic potential of Lewis lung carcinoma (3LL) in
      mice: role of alpha-6 integrin phosphorylation.
AB  - The involvement of protein kinase c (PKC) in the mechanism underlying the
      antimetastatic properties of triazenes was studied in C57BL/6 mice bearing Lewis
      lung carcinoma (3LL). In vivo and in vitro treatment with temozolomide, an in
      vitro active analogue of dacarbazine, or calphostin c produced a concentration
      dependent reduction of spontaneous and artificial metastases. Both agents reduced
      the ability of 3LL cells to adhere to endothelium. Diethylaminoethyl (DEAE)
      sepharose chromatography of cell extracts revealed that incubation of 3LL cells
      with 12-O-tetradecanoylphorbol-13-acetate (TPA) caused a rapid translocation of
      protein kinase c activity from cytosol to the membrane fraction. Membrane PKC
      activity induced by TPA was reduced by 60% after treatment with temozolomide.
      Coincident with these changes, TPA induced phosphorylation of alpha-6 integrin,
      whereas temozolomide or calphostin c abolished the appearance of this
      phosphoprotein. These results suggest that temozolomide reduced metastatic
      potential by interfering with alpha-6 phosphorylation induced by PKC activation.

PMID- 7640050
TI  - The effect of different routes of administration of 5-fluorouracil on thymidylate
      synthase inhibition in the rat.
AB  - A rat colon tumour model of liver metastases was used to administer 5
      fluorouracil (5FU) by intraperitoneal (i.p.) bolus injection (50 mg/kg), isolated
      liver perfusion (ILP, 150 mg/kg) and hepatic artery infusion (HAI, 50 mg/kg). The
      biochemical effect of 5FU, delivered by different routes, on its target enzyme
      thymidylate synthase (TS) was studied in both tumour and normal tissues of the
      rat. In tumour tissue, only small differences were observed in the extent of TS
      inhibition. A pronounced inhibition of TS was observed 3 h after 5FU
      administration by all routes, but was followed by a recovery of TS activity
      within 24 and 48 h. Effects of 5FU on normal tissues were diverse. In liver, TS
      activity increased 6-fold after ILP and HAI administration of 5FU, and a 2-fold
      increase of FdUMP binding to TS was seen for all routes of administration. In
      intestinal mucosa, both induction of TS activity (by ILP) and inhibition of TS
      activity (by HAI) were observed, while i.p. injection did not cause major
      changes. TS activity and FdUMP binding to TS in bone marrow was strongly
      inhibited after administration of 5FU by all routes, but administration by ILP
      seemed slightly advantageous, since a smaller extent of TS inhibition was
      observed compared to the other routes of administration. 5FU given by ILP had a
      small antitumour effect in this colon tumour model, while HAI administration had
      no antitumour activity. Since this difference in antitumour activity could not be
      related to differences in TS inhibition in the tumour, the RNA-directed mechanism
      of action of 5FU could be involved. Focusing on the effects of TS, we may
      conclude that the ILP administration of 5FU offered the important advantage of a
      lack of severe TS inhibition in normal tissues, which corresponds with the low
      systemic toxicity observed.

PMID- 7640051
TI  - Influence of molecular weight on passive tumour accumulation of a soluble
      macromolecular drug carrier.
AB  - The molecular weight-dependence of tumour capture of N-(2
      hydroxypropyl)methacrylamide (HPMA) copolymers (fractions of mw 22,000-778,000)
      was studied in vivo using subcutaneous (s.c.) Sarcoma 180 or B16F10 melanoma
      models. At 10 min, all fractions were already detectable in the tumour (1.5-3% of
      dose administered per gram) and those of molecular weight greater than the renal
      threshold showed progressive tumour accumulation up to 20% of dose administered
      per gram after 72 h in the Sarcoma 180 model. Tumour-selective uptake was
      confirmed for all copolymer fractions in both tumour models and in the sarcoma
      180 model, the ratio (accumulation index, AI) of the AUC in tumour to AUC in
      skeletal muscle (a typical normal tissue) increasing from six to 12 with
      increasing copolymer molecular weight. The tumour/blood AI was greater (1-3) in
      the Sarcoma 180 model than the B16F10 melanoma model (0.4-1.0).

PMID- 7640052
TI  - Patterns of childhood cancer mortality: America, Asia and Oceania.
AB  - Age-standardised mortality rates for childhood cancers for the calendar period
      1950-1989 were reviewed for 22 countries (Canada, U.S.A., 10 Latin American
      countries or territories, Egypt, seven countries or territories from Asia,
      Australia and New Zealand) using data from the World Health Organization
      database. The highest mortality rates (between 6 and 7.5/100,000 boys, between 5
      and 6/10,000 girls) for all childhood neoplasms were registered in Latin American
      countries (Uruguay, Cuba, Argentina, Costa Rica), Kuwait, New Zealand and
      Singapore. Rates were low in most developed countries, such as Canada, U.S.A.,
      Australia, Japan and Israel (3.5 to 4.5/100,000). The pattern was similar for
      leukaemias, which account for approximately 50% of all childhood cancer
      mortality. From the 1960s onwards, a 50% decline in childhood cancer mortality
      was observed in the U.S.A. and Canada, and substantial declines were also
      observed in other developed countries, such as Australia, Israel and Japan. The
      pattern was much less favourable for other areas of the world, including Latin
      America and a few countries from Asia for which there were data. These declines
      in childhood cancer mortality are essentially attributable to improved management
      of the disease. The delay observed in the decline in mortality for most
      developing countries emphasises the scope and the importance of extending
      adequate treatments for childhood cancers to these areas of the world.

PMID- 7640053
TI  - Phase II study of rapid-scheduled etoposide in paediatric soft tissue sarcomas.
AB  - Twenty three patients with paediatric soft tissue sarcomas who had relapsed or
      refractory disease were treated with a rapid schedule of intravenous etoposide
      (100 mg/m2 daily on three consecutive days, weekly over 3 weeks). The regimen was
      well tolerated with predictable myelotoxicity. In 19 patients with
      rhabdomyosarcoma, there was a response rate of 42%. This appears to be better
      than previously reported with conventional three weekly schedules. These data
      indicate that for rhabdomyosarcoma, as for some other tumours, a divided dose
      regimen may be the optimal schedule and is worthy of further evaluation.

PMID- 7640055
TI  - Therapy of carcinoma of the oesophagus: either attempt it not or succeed.

PMID- 7640054
TI  - Comparison of continuous infusion and bolus administration of ifosfamide in
      children.
AB  - The pharmacological effects of ifosfamide (IFO) are dependent on its metabolism
      which may vary between different modes of administration. This was studied in 17
      patients who received both a continuous infusion (9 g/m2 over 72 h) and repeated
      bolus administration (3 g/m2 every 24 h for 3 days). Concentrations of IFO and
      its metabolites were determined in plasma and urine. There was up to 70% less of
      the dechloroethylated metabolites in plasma following bolus administration
      compared to continuous infusion. Since dechloroethylation results in the
      formation of the toxic metabolite chloroacetaldehyde, this difference in
      metabolism may have an impact on the toxicity of IFO. There were no other
      consistent differences between the two modes of administration. Auto-induction of
      IFO metabolism, with an increase in dechloroethylated metabolites, was observed
      for both modes of administration. In conclusion, apart from dechloroethylation,
      there is little difference between these two modes of administration. However,
      during multiple cycles of IFO therapy such differences could have a significant
      effect.

PMID- 7640056
TI  - Cutaneous T-cell lymphoma: molecular genetics, immunology and pathogenesis.

PMID- 7640057
TI  - Conformal radiation treatment: a critical appraisal.
AB  - Significant technical advances have improved the precision of radiation treatment
      of human malignancies and permitted dose-escalation studies. However, a number of
      challenges remain, particularly in the clinical and radiobiological aspects of
      radiotherapy. Even with these deficiencies, it is likely that improved overall
      treatment results will be forthcoming with 3DCRT. Nevertheless, the cost
      effectiveness of this approach needs to be assessed, based on the magnitude of
      the improvement in the treatment of various disease sites.

PMID- 7640058
TI  - The present role of laparoscopy in gynaecological oncology; the EORTC point of
      view.

PMID- 7640059
TI  - Gene therapy for cancer.

PMID- 7640060
TI  - Genetic testing of the common cancers: potential and problems.

PMID- 7640061
TI  - High dose therapy and ABMT rescue in lymphoma and solid tumours.

PMID- 7640062
TI  - High-dose chemotherapy of breast cancer: current status and developmental
      strategies.

PMID- 7640063
TI  - High-dose chemotherapy in tumours other than lymphomas and breast cancer.

PMID- 7640064
TI  - Haemopoietic growth factors: uses and misuses.

PMID- 7640065
TI  - Combined modality treatment in small cell lung cancer (SCLC).

PMID- 7640066
TI  - Chemotherapy in head and neck cancer.

PMID- 7640067
TI  - Ovarian cancer--new insights into systemic therapy.

PMID- 7640068
TI  - Taxoids.

PMID- 7640069
TI  - New endocrine agents in the treatment of breast cancer.

PMID- 7640071
TI  - Biology and therapy of Hodgkin's disease.

PMID- 7640070
TI  - Topoisomerase I inhibitors and other new cytotoxic drugs.

PMID- 7640072
TI  - Signal transduction inhibitors.

PMID- 7640073
TI  - Retinoids in oncology.

PMID- 7640074
TI  - Developments in radiotherapy.

PMID- 7640075
TI  - Recent developments in the biology and management of advanced bladder cancer.

PMID- 7640076
TI  - Controversies in testicular cancer management.

PMID- 7640077
TI  - Recent advances in the management of lymphoma.

PMID- 7640078
TI  - Molecular basis of radioresistance.

PMID- 7640079
TI  - Flow cytometric and cytophotometric DNA analysis cannot predict subsequent tumour
      recurrence in pathological stage IIA/B non-seminomatous testicular germ cell
      tumour patients who do not receive adjuvant chemotherapy.

PMID- 7640080
TI  - Exceptional toxicity of 5-fluorouracil and interferon-alpha in a patient with
      hepatocellular carcinoma.

PMID- 7640081
TI  - A double-blind comparison study of tropisetron and placebo in the prevention of
      radiation-induced diarrhoea.

PMID- 7640082
TI  - Prognostic significance of TGF-beta 2 expression in female breast cancer.

PMID- 7640083
TI  - Biological response to intrahepatic adoptive immunotherapy with autologous
      interferon activated macrophages.

PMID- 7640084
TI  - Determination of oestrogen receptor by enzyme immunoassay.

PMID- 7640085
TI  - Mutational analysis of the MCC gene by single-strand conformational polymorphism
      analysis.

PMID- 7640086
TI  - Defecography.

PMID- 7640087
TI  - Defecography.
AB  - Defecography, a dynamic imaging modality, plays an important role in the
      diagnosis of functional and morphologic abnormalities of the anorectal region. We
      have here summarized the principle and techniques as well as observations of
      defecography, with special emphasis on morphologic measurements, clinical
      relevance, and limitations. The application of MR imaging in examination of
      anorectal function has also been addressed.

PMID- 7640088
TI  - Videoradiography of free jejunal grafts for rehabilitation of speech in
      laryngectomized patients.
AB  - In laryngectomized patients a tracheo-esophageal artificial fistula can be used
      to achieve air flow from the trachea to the esophagus during speech. A one-way
      plastic valve is often used for the fistula. A free jejunal graft between the
      trachea and the esophagus can also be used. To avoid aspiration the transplant is
      attached to the submental area giving the graft a siphon-like shape. We performed
      23 videoradiographic examinations using high-density barium in 14 such patients.
      The aim was to evaluate the protective function of these grafts against
      aspiration. Penetration of the bolus and a small amount of residual contrast
      material in the ascending limb of the graft was a normal finding. If the standard
      barium bolus reached the descending limb at any time during the examination, this
      was a sign of aspiration hazard. To avoid aspiration, the vertex of the speech
      siphon should be higher than the level of the hypopharyngeal anastomosis.

PMID- 7640089
TI  - Dynamic Octreotide scintigraphy in neuroendocrine tumours.
AB  - The purpose of the present study was to investigate the optimal time for
      scintigraphy after injection of the radio-labelled somatostatin analogue,
      Octreotide. A secondary purpose was to evaluate the value of SPECT. One SPECT
      study and up to 4 whole body scans were performed in 22 patients with
      neuroendocrine tumours 0.5, 5, 24 and 48 hours after an injection of 110 MBq In
      DTPA Octreotide. A total of 98 scintigrams were studied. A pathological uptake
      was found in 19 of the 22 patients. In 3 cases, early scintigrams (0.5 and 5
      hours after injection) were of the most value whereas late scintigrams (24 and 48
      hours) were the best in 4 cases. SPECT was found to be of value in 13 of 21
      cases. For correct interpretation of Octreotide scintigraphy it is necessary to
      obtain both early and late scintigrams as well as a SPECT study.

PMID- 7640090
TI  - Colo-colonic intussusception caused by lipoma. Case reports.
AB  - Intussusception is primarily seen among children, most often as idiopathic
      ileocolic intussusception (1, 4), and only 5 to 16% of all intussusceptions are
      seen in adults (1, 8). In contrast to childhood invagination, in adults
      underlying pathologic processes are identified in 18 to 90% (1, 8). This report
      presents 2 cases of colo-colonic intussusception caused by a colonic lipoma. The
      ultrasonic features of this benign tumour are rather characteristic. A definitive
      diagnosis can be provided by CT.

PMID- 7640091
TI  - Ultrasonically guided insertion of a peritoneo-gastric shunt in patients with
      malignant ascites.
AB  - PURPOSE: A new method for internal drainage of malignant ascites is presented in
      5 patients with symptomatic malignant ascites. MATERIAL AND METHODS: US-guided
      percutaneous gastrostomy and paracentesis were performed using the Seldinger
      technique. A 2.5-mm Cope-loop catheter was inserted in the fluid-filled stomach.
      In the lower abdomen the proximal part of a Denver peritoneo-venous shunt was
      introduced after dilation up to 4.8 mm. The pump chamber was sutured to the skin.
      The distal part of the Denver shunt was cut a few cm from the pump chamber and
      connected to the gastrostomy catheter. When pumping, ascites is shunted to the
      stomach lumen. RESULTS: The insertion presented no complications, and all shunt
      systems initially functioned well. However, the shunts had to be removed within
      the first 2 weeks because of mechanical problems such as clotting, leakage, and
      peritoneal septum formation. No infections were reported. CONCLUSION: The
      peritoneo-gastric shunt may present a therapeutic alternative in selected
      patients, but the mechanical problems have first to be solved.

PMID- 7640092
TI  - Yield and complications in ultrasound-guided biopsy of abdominal lesions.
      Comparison of fine-needle aspiration biopsy and 1.2-mm needle core biopsy using
      an automated biopsy gun.
AB  - A series of 458 consecutive ultrasound-guided biopsies in 347 patients-171 fine
      needle aspiration biopsies (FNABs) and 287 1.2-mm needle core biopsies (NCBs)-was
      analysed for diagnostic yield and complications. FNAB was diagnostic in 107 (64%)
      biopsies of focal lesions with a correct diagnosis of malignancy in 86 of 125
      biopsies (69%) and of benign disease in 21 of 43 (49%) biopsies. NCB provided a
      correct diagnosis in 189 (90%) biopsies for focal lesions, divided into 140 of
      159 (88%) correct for malignancy and 49 of 50 (98%) correct for benign disease.
      In 69 patients examined with both FNAB and NCB on the same occasion, 50 out of 55
      malignant lesions were identified with NCB but only 34 with FNAB; all 14 benign
      lesions were correctly identified by NCB, and only 6 by FNAB. Clinical relevant
      bleeding complications occurred in 6 out of 458 biopsies (1.3%)-3 out of 287
      following NCB (1.0%) and 3 out of 171 following FNAB (1.8%). It is concluded that
      if FNAB is replaced with 1.2-mm NCB using an automated biopsy gun, the diagnostic
      accuracy for abdominal lesions increases significantly (p < 0.001), while the
      complication rate remains the same.

PMID- 7640093
TI  - Differentiation between contained and noncontained lumbar disk hernias by CT and
      MR imaging.
AB  - AIMS: The investigation was carried out in order to compare the accuracy of CT
      and MR imaging in depicting whether disk hernias were contained by the posterior
      longitudinal ligament (PLL). This is crucial in the evaluation of patients who
      are possible candidates for percutaneous nucleotomy, which is considered
      effective only in contained hernias. RESULTS: Of 124 pathologic disks examined in
      114 patients, CT was more accurate than MR imaging in 7 patients due to
      misinterpretation of the integrity of the PLL by MR. These hernias were therefore
      erroneously classified as noncontained. There was consistency between the
      classification by CT and MR imaging in the other 117 disks, of which 109 were
      correct. Both methods overstaged a large hernia that was contained by the PLL,
      and failed to demonstrate that 7 others were noncontained. CONCLUSIONS: CT, which
      has higher sensitivity in depicting calcifications, representing further
      contraindications to percutaneous nucleotomy, is therefore recommended as the
      primary examination in these patients. Additional MR imaging should be considered
      if the results of CT are equivocal or at variance with the clinical presentation.

PMID- 7640094
TI  - CT-diskography in patients with sciatica. Comparison with plain CT and MR
      imaging.
AB  - AIMS: The findings at CT-diskography (CT-D), including recording of the pain
      introduced at contrast injection, were compared with plain CT and MR imaging in
      111 disks in 101 patients aged 18 to 68 years. RESULTS: Six disks which were
      normal at CT had normal CT-D and 5 of them had normal signal on MR imaging. The
      degree of annular degeneration and the depth of the annular tears were
      significantly associated with each other and with loss of disk height, but not
      with size or location of the hernias. Only the depth of the tears was
      significantly associated with loss of signal on MR. However, frequently complete
      annular tears and severe annular degeneration were seen in association with small
      bulges and hernias, even in disks with normal or slightly reduced signal on MR
      and with normal height. The type and intensity of the pain introduced were
      associated with each other and with the depth of the annular tears, but not with
      the degree of annular degeneration, size of the hernia or the MR signal intensity
      of the disks. CONCLUSIONS: Annular degeneration and tears on one hand, and the
      type and intensity of pain introduced on the other, seem to be related than
      separate phenomena.

PMID- 7640095
TI  - Low-field MR imaging of the spine. A comparative study of a traditional and a
      new, completely balanced gradient-echo sequence.
AB  - PURPOSE: To evaluate a new steady-state sequence in the delineation of the
      various structures in the spine at low-field MR imaging with a very high
      homogeneity of the main field. METHODS: 49 patients underwent 53 examinations
      with both a traditional T1-weighted gradient-echo (PS) sequence and a new
      completely balanced steady-state 3-D (CBASS3D) sequence; 20 examinations included
      the cervical spine, 8 the thoracic spine and 25 the lumbar spine. All 106
      examinations were reviewed twice regarding visibility of selected structures in
      the spinal region and diagnostic usefulness. RESULTS: The CBASS3D sequence
      delineated the medulla, nerve roots, CSF, the intervertebral discs and the
      posterior longitudinal ligament significantly better than the PS sequence. Disc
      hernia was also better visualised (p < 0.01). There were significantly more
      artefacts on images obtained with the CBASS3D sequence, but they were usually
      outside the region of interest and occurred less frequently over time due to
      increased experience of the staff. Both reviewers found the diagnostic usefulness
      of CBASS3D to be superior compared to that of PS and excellent for diagnostic
      purposes. CONCLUSION: The CBASS3D sequence is a considerable improvement in the
      visualisation of degenerative changes of the spine at low-field MR imaging.

PMID- 7640096
TI  - MR imaging of tubo-ovarian abscess.
AB  - PURPOSE AND MATERIAL AND METHODS: MR findings of 9 surgically proven tubo-ovarian
      abscesses were analyzed in 8 patients. The images were evaluated for signal
      intensity characteristics and morphologic appearance of the mass, and presence of
      secondary changes in adjacent pelvic organs and structures. RESULTS: The signal
      intensity of the lesions on T1-weighted images was hypointense to the surrounding
      muscle and myometrium in 5 patients, isointense in 3 and hyperintense in 1. On T2
      weighted images the signal intensity was hyperintense (n = 6) or heterogeneous (n
      = 3). A thin rim (1-3 mm) with hyperintensity on T1-weighted images was noted in
      the innermost aspect of the masses. Other findings were ill-defined margin,
      thickened wall, multiple internal septa, shading and gas collection. "Mesh-like"
      linear strands were noted in the pelvis in all patients, with involvement of
      adjacent pelvic organs in 7 and lymphadenopathy in 3. CONCLUSIONS: In this
      limited number of cases MR imaging showed great potential for demonstrating the
      extent of the disease, characterizing the lesions and making a specific
      diagnosis.

PMID- 7640097
TI  - Survival of patients after resection for lung cancer. Predictive value of staging
      by CT vs thoracotomy.
AB  - PURPOSE: The predictive value of staging of primary lung cancer by CT and
      thoracotomy with respect to survival was assessed in a series of 151 consecutive
      patients. MATERIAL AND METHODS: The new international staging system for lung
      cancer was used, with an additional indeterminate stage employed for cases in
      which a definite classification was impossible by CT. RESULTS: The survival rate
      curves for the stage groups assessed at CT and thoracotomy showed moderate to
      good parallelism. The patients with tumor stage I at thoracotomy but
      indeterminate or IIIa at CT had a significantly lower survival rate than those
      scored stage I at both. It was concluded that a sign of tumor spread obtained at
      any of the investigations should lead to an active approach, increasing the
      radicality of surgery or omitting noncurative operations.

PMID- 7640098
TI  - Echo-planar MR cerebral blood volume mapping of gliomas. Clinical utility.
AB  - Neovascularization is a common phenomenon in gliomas. MR imaging cerebral blood
      volume (CBV) mapping utilizes ultrasfast echo-planar imaging and simultaneous use
      of gadolinium-based contrast material. To determine the utility of MR CBV mapping
      in the clinical evaluation of gliomas, we followed 15 patients with serial
      studies. This technique provided functional information that was not evident with
      conventional CT or MR imaging. Low-grade tumors demonstrated homogeneously low
      CBV, while high-grade tumors often showed areas of both high and low CBV. The
      maximum tumor CBV/white matter ratio was compared between low- (n = 3) and high
      grade gliomas (n = 5) in patients without previous treatment and with histologic
      verification (n = 8) and was significantly higher in high-grade gliomas (p <
      0.01). High CBV foci in nonenhancing tumor areas were present in 2 cases. The
      distinction between radiation necrosis and active tumor could be made correctly
      in 3 of 4 cases. The information provided by MR CBV mapping has the potential to
      be an adjunct in the clinical care of glioma patients.

PMID- 7640100
TI  - A 3-D method for delineation of activity distributions and assessment of
      functional organ volumes with SPECT.
AB  - The distribution volume of an organ may have a clinical impact in many cases and
      various methods have been designed to make volume assessments. In this paper, we
      describe a new method for delineation of the distribution outline and volume
      determination. The method is based on smoothing, differentiation, image
      relaxation and voxel counting of single photon emission computer tomography
      (SPECT) image sets with 3-D operators. A special routine corrects for the
      inherent thickness of the voxel-based outline. Phantom experiments, using a SPECT
      system with LEGP-collimator and a 64 x 64 acquisition matrix with 6.3 x 6.3 mm2
      pixel size, demonstrated good correlation between the measured and the true
      volumes. For volumes larger than 120 cc the correlation coefficient was 0.9999
      with SE 1.0 cc and an average relative deviation of 0.49%. For volumes below 120
      cc, the accuracy was impaired due to low resolution power. By improving the
      system spatial resolution with an LEHR-collimator and a smaller pixel-size (4.1 x
      4.1 mm2), good accuracy was achieved also for volumes in the range from 3 to 120
      cc. Measurements of 15 differently shaped phantoms of volumes between 3 and 104
      cc demonstrated high correlation between measured and true volumes: R = 0.9921
      and SE = 0.74 cc (5.3%). For volumes as small as 3 and 5 cc, the difference
      between the true and the assessed volume was 0.6 cc. The reproducibility of the
      method was within 3% for volumes above 120 cc and within 7% for volumes
      below.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7640099
TI  - Pituitary microadenoma. MR appearance and correlation with CT.
AB  - Twenty surgically proven pituitary microadenomas were examined with MR imaging
      and CT. MR demonstrated 20 of 20 microadenomas: 90% of the tumors were
      hypointense on T1-weighted images before Gd-DTPA administration and in 45% the
      tumors were more clearly delineated postcontrast. CT demonstrated 19 of 20
      diagnosed microadenomas: showing low attenuation in 85% of the tumors
      precontrast. Iohexol facilitated delineation of the tumors in 45%. Focal
      enlargement of the gland and diaphragma sellae convexity were more useful than
      infundibular tilting and sellar-floor erosion as ancillary findings supporting
      the diagnosis. In general, CT and MR agreed regarding the microadenomas size and
      location, measurement of enlarged intrasellar contents, detection of the
      diaphragma sellae bulge, and demonstration of infundibulum abnormality. CT was
      more sensitive than MR in identifying sellar-floor erosion. We suggest that CT be
      the first method for demonstration of microadenomas.

PMID- 7640101
TI  - Comparative study of the dialysability of iobitridol and iohexol in the rat with
      impaired renal function.
AB  - PURPOSE: To assess the dialysability of iobitridol, a comparative study with
      iohexol was conducted in the rat over 4 hours. MATERIAL AND METHODS: After
      ligature of the renal veins and arteries, a group of animals was submitted to
      continuous peritoneal dialysis, while the remainder were not. RESULTS: In the
      event of total renal failure, biliary excretion rose from 0.4 to 9% for
      iobitridol and from 2 to 16% for iohexol. In the rats submitted to peritoneal
      dialysis, biliary excretion decreased to 5% in the iobitridol group and to 13% in
      the iohexol group. Further, 18% of the test substances were eliminated in the
      dialysis liquid. CONCLUSIONS: As their physicochemical characteristics are very
      similar, the differences between the biliary excretion levels of these 2 media
      may be caused by a factor related to their respective molecular conformations.

PMID- 7640102
TI  - Contrast enhancement of the upper abdomen evaluated by CT. A comparison between
      iohexol 350 mg I/ml and iopamidol 370 mg I/ml.
AB  - The non-ionic monomeric contrast media iopamidol and iohexol were compared
      concerning enhancement in the organs of the upper abdomen in CT. The average peak
      enhancement above the base line for the 2 contrast media in the liver, vena cava,
      aorta and spleen was calculated. No difference between the contrast media was
      found with regard to increase in contrast enhancement. No correlation between the
      peak enhancement and body weight and body surface was found with either of the 2
      contrast media.

PMID- 7640103
TI  - Deuterium MR in vivo imaging of the rat eye using 2H2O.
AB  - In vivo deuterium MR imaging (2H MR) was investigated in rats after
      intraperitoneal administration of deuterated saline, and a dynamic study of the
      water movement in rat eyes was performed. Deuterium MR imaging was carried out by
      means of a gradient-echo (GRE) and a spin-echo (SE) pulse sequence. The rat eye
      was imaged in 2H MR more selectively by SE than by GRE, but a lower signal-to
      noise ratio was obtained in 2H MR imaging using the SE sequence. The MR signal
      intensity of the rat eye was followed by a 3-compartment model, which enabled
      determination of the flow rate constant of the water in the eye (0.359/min).
      Deuterium MR imaging is useful to visualize the dynamic change of water in rat
      eyes using 2H MR at the same magnetic field (2 T) that can also be used for
      conventional MR imaging in humans.

PMID- 7640104
TI  - Efficient memory management strategy in hypermedia with interactive MR images.
AB  - When composing hypermedia with interactive image sets the main problem is to
      allocate minimal memory of random access memory (RAM). The stand-alone product
      should be accessible to the public and not require too much memory to maintain
      interaction between the images and the text. We designed a new hypermedia
      application using SuperCard and image stacks in PICS format running on a
      Macintosh LC computer. Memory use was effective since the images were kept in
      external files outside the application. On browsing cards the images were
      requested from the image file and each image was displayed within about 1 second
      as a floating frame on top of the card in the top window. Interactivity when
      presenting, for example, anatomical parts was achieved by bitmap objects which
      were activated through the image by pointing at them through the image. By
      pointing at a text object the corresponding anatomical bitmap object was
      visualised through the image. The stand-alone version of the application with up
      to 100 cards runs on a 2 Mb RAM set-up. The maximum sizes of the external image
      stacks are not dependent on the RAM size.

PMID- 7640105
TI  - Leadership challenges after downsizing.

PMID- 7640106
TI  - Making sense of work redesign.

PMID- 7640107
TI  - Service redesign through the continuum of care: a total quality improvement
      approach.

PMID- 7640108
TI  - Multidisciplinary shared governance model in a union setting.

PMID- 7640109
TI  - Consortium program prepares nurses for the shift from hospital- to community
      based nursing.

PMID- 7640110
TI  - Staff member support in continuous performance improvement.

PMID- 7640111
TI  - Organizational discipline.

PMID- 7640112
TI  - Lessons observed: why reegineering flounders or succeeds.

PMID- 7640113
TI  - The Noisebusters: a continuous quality improvement approach to managing noise.

PMID- 7640114
TI  - Cerebral blood flow during induced hypotension.

PMID- 7640115
TI  - Increase in Mallampati score during pregnancy.
AB  - A photographic version of the Mallampati test was developed and applied to 242
      pregnant patients at 12 weeks' gestation and again at 38 weeks' gestation. At 38
      weeks the number of grade 4 cases had increased by 34% (P < 0.001). This is in
      agreement with other evidence which suggests that difficult laryngoscopy is
      slightly more frequent in obstetrics (1.7%) than in general surgery (1.3%). The
      increase in Mallampati score correlated with gain in body weight (r = 0.3, P <
      0.001), which gives some support to the concept that fluid retention is the
      underlying cause. We conclude that pharyngeal oedema causes some hindrance to
      tracheal intubation in obstetrics, but not enough to explain the high failure
      rate reported. A case is made for rationalizing the management of difficult
      intubation. Our data also show that more research is needed on factors which
      affect Mallampati's test, particularly neck extension.

PMID- 7640116
TI  - I.v. tenoxicam for analgesia during caesarean section.
AB  - We have studied the analgesic efficacy of a single i.v. dose of tenoxicam 20 mg,
      given 10 min before induction of anaesthesia in 25 patients undergoing elective
      Caesarean section. Another group of 25 similar patients served as controls.
      Nalbuphine consumption in the first 24 h after operation was reduced by 50% when
      tenoxicam was given. The median time to first request for analgesia was increased
      from 25 to 110 min in the tenoxicam group. Subjective experiences of pain and
      sedation were significantly greater in the control group up to 24 h after
      operation. The haemodynamic variability after intubation was of shorter duration
      in the tenoxicam group. There was no significant difference in incidence and
      severity of postoperative nausea and vomiting between the two groups. The
      surgeon's assessment of uterine relaxation and bleeding, using a visual analogue
      score, and infant well-being, as judged by Apgar score and cord blood-gas
      analysis, showed no significant difference between the two groups. There was no
      evidence of premature closure of the ductus arteriosus or pulmonary hypertension.
      We conclude that a single i.v. dose of tenoxicam is a useful pretreatment to
      minimize the haemodynamic variability of light general anaesthesia at induction
      delivery and in reducing 24 h postoperative opioid consumption.

PMID- 7640117
TI  - Effect of transdermal hyoscine on nausea and vomiting after surgical correction
      of prominent ears under general anaesthesia.
AB  - In a double-blind, randomized study, we have compared the efficacy of transdermal
      hyoscine with placebo in the reduction of nausea and vomiting in 50 patients, ASA
      I-II, after surgical correction of prominent ears under general anaesthesia. In
      the placebo group, 28%, 4% and 48% of patients suffered nausea, retching and
      vomiting, respectively, during the first 24 h after anaesthesia. The
      corresponding values in the hyoscine group were 12%, 0% and 16% (P < 0.01). In
      the placebo group more patients (48%) needed droperidol as an antiemetic compared
      with the hyoscine group (16%; P < 0.05). There was significantly more sedation in
      the hyoscine group.

PMID- 7640118
TI  - Prediction of infusion rates of vecuronium using the bolus test dose technique.
AB  - Fifty neurosurgical patients were given loading doses of vecuronium 0.1 mg kg-1
      followed by boluses of 1, 2 or 4 mg after return of T1 of the train-of-four.
      Neuromuscular function was assessed simultaneously by palpation of the great toe
      after peripheral nerve stimulation of the lateral popliteal nerve using a
      handheld nerve stimulator and also using a Relaxograph attached to one arm. The
      time taken for the return of T1 after the bolus dose was recorded and an infusion
      of vecuronium was begun and subsequently adjusted to maintain steady state
      neuromuscular block. It was possible to predict the infusion rate of vecuronium
      from the duration of action of a 2-mg or 4-mg but not a 1-mg bolus dose using the
      handheld stimulator. The infusion rate could also be predicted from the duration
      of action of the initial loading dose.

PMID- 7640119
TI  - Continuous measurement of cardiac output during aortic cross-clamping by the
      oesophageal Doppler monitor ODM 1.
AB  - We have compared the Doppler against the thermodilution technique for measurement
      of cardiac output in six patients during aortic surgery. The correlation
      coefficient between the two methods was between 0.76 and 0.84 during the
      different periods of the operation. Using the integral nomogram instead of direct
      calibration, the Doppler system underestimated cardiac output in atherosclerotic
      patients. However, the Doppler method did register accurately significant changes
      in cardiac output.

PMID- 7640120
TI  - Perioperative plasma endothelin-1 concentrations and vasoconstriction during
      prolonged plastic surgical procedures.
AB  - The role of endothelin-1, a potent vasoconstrictor released by vascular
      endothelium, in the vasoconstriction that develops after prolonged operations is
      not clear. This study was performed in order to determine if there was any
      relationship between endothelin-1 and the degree of vasoconstriction during
      prolonged plastic surgery. Plasma concentrations of endothelin-1, skin-forearm
      temperature gradient (Tgrad), rectal temperature, mean arterial pressure (MAP)
      and heart rate (HR) were measured at nine predetermined times before, during and
      after operation in nine women undergoing breast reconstruction with a pedicled
      transverse rectus abdominis musculocutaneous flap. Development of cutaneous or
      fat necrosis of the flap was assessed clinically and with ultrasound.
      Concentrations of endothelin-1 before induction were increased (median 8.9 (25
      75% quartiles 5.5-12.5) pg ml-1). During operation they were approximately 3 pg
      ml-1 and after operation approximately 5 pg ml-1. Tgrad was approximately 4
      degrees C before induction and after operation, indicating marked
      vasoconstriction; during operation it was about zero, indicating vasodilatation.
      There was a statistically significant correlation between endothelin-1
      concentrations and Tgrad (Spearman non-linear correlation) (r = 0.32, P = 0.004)
      and between endothelin-1 and MAP (r = 0.25, P = 0.02), but not between endothelin
      1 and HR or development of minor cutaneous or fat necrosis of the flap (five
      patients). We conclude that increased plasma concentration of endothelin-1 is
      associated with the extent of peripheral vasoconstriction.

PMID- 7640121
TI  - Effect of total flow rate on the concentration of degradation products generated
      by reaction between sevoflurane and soda lime.
AB  - We have compared concentrations of degradation products in the circle system
      during sevoflurane anaesthesia at different fresh gas flows. Twenty-four patients
      underwent sevoflurane anaesthesia with fresh gas flows of 1 litre min-1 (1L
      group), 3 litre min-1 (3L group), or 6 litre min-1 (6L group) (n = 8 in each
      group). During anaesthesia, the concentrations of degradation products were
      measured every hour, and the temperature of soda lime, end-tidal carbon dioxide
      concentrations, inspired and end-tidal sevoflurane concentrations, and carbon
      dioxide elimination were measured. CF2 = C (CF3)-O-CH2F (compound A) was the only
      degradation product detected. The mean maximum concentration of compound A was
      19.7 (SD 4.3) ppm in the 1L group, 8.1 (2.7) ppm in the 3L group and 2.1 (1.0)
      ppm in the 6L group (P < 0.05). The maximum temperature of soda lime was 44.6
      (1.5) degrees C in the 1L group, 37.0 (4.4) degrees C in the 3L group and 29.1
      (5.1) degrees C in the 6L group (P < 0.05). There were no significant differences
      in end-tidal sevoflurane concentration or mean carbon dioxide elimination between
      the groups. Only compound A was detected following anaesthesia, with higher
      concentrations observed at lower flow rates.

PMID- 7640122
TI  - Analgesic and hypnotic effects of subanaesthetic concentrations of xenon in human
      volunteers: comparison with nitrous oxide.
AB  - The purpose of this study was to examine the effects of xenon and nitrous oxide
      in equipotent doses of 0.3 MAC on pain threshold and auditory response time in
      six healthy male volunteers. Compared with 100% oxygen inhalation, xenon and
      nitrous oxide significantly increased the pain threshold as measured by a radiant
      heat algometer. There was no significant difference in analgesic effects between
      xenon and nitrous oxide. Xenon significantly prolonged the response time to
      auditory stimuli compared with 100% oxygen, but nitrous oxide did not. The
      inhibitory effect of xenon on the auditory response time was significantly
      greater than that of nitrous oxide. The same six volunteers were studied to test
      if naloxone antagonized analgesia induced by xenon or nitrous oxide. The
      analgesic effects of xenon and nitrous oxide did not differ with or without
      naloxone.

PMID- 7640123
TI  - The P300 event-related potential during propofol sedation: a possible marker for
      amnesia?
AB  - We have studied the effects of conscious sedation with propofol on long latency
      components of the auditory event-related potential (ERP) in 10 normal volunteers
      (aged 21-41 yr) receiving propofol 75 micrograms kg-1 min-1 i.v. We examined the
      effects of propofol on ERP amplitudes and latencies, and their relationship to
      delayed recognition performance using a verbal memory test, a selective attention
      task (button pushing) and serum concentrations of propofol. During infusion of
      propofol, subjects were mildly sedated, oriented and readily responsive to verbal
      commands. ERP were recorded from monopolar FZ, CZ and PZ electrodes. We used a
      standard paradigm requiring selective attention to randomly occurring stimuli
      associated with a task (button push). The peak-to-peak amplitudes and latencies
      of the N2 and P3 waves were obtained before and during infusion, and 15, 100 and
      170 min after infusion. Propofol produced a 70% decrease in the amplitude of P3
      (P < 0.0001) from baseline and a 50% increase in reaction time. The differential
      response to target compared with non-target stimuli was maintained during
      infusion for both N2 and P3. Memory performance correlated more strongly with
      changes in P3 amplitude (r = 0.59) than with serum propofol concentrations (r = 
      0.07), although this correlation with memory did not reach statistical
      significance (P = 0.08). We conclude that P3 amplitude was profoundly affected by
      propofol given in sedative concentrations.

PMID- 7640124
TI  - Visually evoked bursts during isoflurane anaesthesia.
AB  - We studied EEG reactivity to visual stimuli during deep isoflurane (1.5-2.05 vol%
      end-tidal concentration) anaesthesia. Twelve patients were anaesthetized with
      isoflurane until burst suppression occurred in the EEG. Red LED goggles were used
      to give visual stimulation of 60 flashes, 4-ms duration each, at a frequency of
      20 Hz. The stimuli, 3-strains of flashes, were given at random intervals. Both
      onset and offset of stimulation evoked bursts. The latency of visually evoked
      bursts was comparable with long latency evoked potentials, which are known to be
      related to cognitive processing. Our data showed that the central nervous system
      reacts strongly to photic stimulation during deep anaesthesia.

PMID- 7640125
TI  - Cerebral blood flow distribution during induced hypotension with haemorrhage,
      trimetaphan or nitroprusside in rats.
AB  - Local cerebral blood flow (CBF) during three types of profound hypotension were
      compared using the quantitative autoradiographic [14]-C iodo-antipyrine method.
      Rats were rendered hypotensive to a mean arterial pressure of 30 mm Hg for 30 min
      by haemorrhage, trimetaphan or nitroprusside during 0.8% halothane anaesthesia.
      During haemorrhagic hypotension, mean local CBF was reduced significantly in all
      except two pontine regions. This reduction in flow ranged from 83% to 41%
      compared with the normotensive control group, with the neocortex and
      telencephalon most affected. During trimetaphan-induced hypotension, local CBF
      was reduced to the same degree and in the same pattern as that during
      haemorrhagic hypotension. In contrast, during nitroprusside-induced hypotension,
      local CBF in many regions of the brain was well maintained (57-101%); although
      local CBF was significantly below control in all cortical and telencephalic
      regions, it was significantly greater in the majority of these regions than in
      the other two hypotensive groups. We conclude that local CBF was significantly
      reduced in the neocortex and telencephalon by hypotension of this degree induced
      by all three methods, but nitroprusside preserved local CBF significantly better
      than the other methods, in these, as in most other regions.

PMID- 7640126
TI  - Selective effects of alfentanil on nociceptive-related neurotransmission in
      neonatal rat spinal cord.
AB  - We have examined the effects of alfentanil on nociceptive-related
      neurotransmission in isolated neonatal rat spinal cord, with particular attention
      to acute tolerance. Electrical stimulation of a lumbar dorsal root was used to
      evoke the monosynaptic reflex (MSR), a slow ventral root potential (sVRP), and
      the dorsal root potential (DRP). Alfentanil (0.5 nmol litre-1 to 1 mumol litre-1)
      depressed sVRP area by a maximum of 85%; EC50 was approximately 2 nmol litre-1.
      The effects of alfentanil were selective for very slow, metabotropically mediated
      sVRP components compared with faster NMDA receptor-mediated components. The MSR
      was unaffected. Alfentanil depressed DRP area by a maximum of 50% at 1 mumol
      litre-1. Naloxone antagonized all alfentanil effects. Morphine depressed sVRP
      area with an approximate EC50 of 90 nmol litre-1, giving an alfentanil:morphine
      potency ratio of 45:1. The effects of alfentanil on sVRP showed no biphasic time
      dependence up to 60 min. Naloxone administered after alfentanil produced a
      significant rebound in sVRP area to a level of 143 (SD 21.3)% above control.
      Thus, in this study there was no evidence for acute tolerance, as measured by a
      decrease in effectiveness over time, but there was evidence as measured by
      rebound following naloxone.

PMID- 7640127
TI  - Red blood cell substitutes: current status.

PMID- 7640128
TI  - Maximum recommended doses of lignocaine are not toxic.
AB  - The maximum recommended doses of lignocaine are frequently exceeded in clinical
      practice as some blocks may need more lignocaine to produce adequate anaesthesia.
      We have examined the success rate of brachial plexus block, possible toxic
      symptoms after a dose of lignocaine 900 mg with adrenaline, and the maximum
      plasma concentration of lignocaine produced in 17 adult patients. In all
      patients, the block was excellent and no toxic symptoms were encountered. The
      highest mean lignocaine plasma concentration was 2.9 micrograms ml-1 45 min after
      the block. We conclude that in brachial plexus block, the dose of lignocaine with
      adrenaline can be as high as 900 mg without fear of toxic symptoms.

PMID- 7640129
TI  - Evaluation of the efficacy and safety of amethocaine gel applied topically before
      venous cannulation in adults.
AB  - We have assessed in a placebo-controlled, double-blind trial, the efficacy and
      safety of an amethocaine gel preparation for alleviating the pain of venous
      cannulation. Forty-two unpremedicated adult patients were allocated randomly to
      receive either amethocaine gel 1 g (4% w/w) or placebo gel 1 g applied to the
      dorsum of the hand for 40 min before venous cannulation. After removal of the
      gel, a 20-gauge cannula was inserted and the pain of cannulation assessed by a
      three-point rank score and a 100-mm visual analogue scale: 90% of patients who
      received amethocaine reported clinically acceptable topical anaesthesia. Both
      verbal rating scores and visual analogue scores for pain were significantly less
      with amethocaine. Slight erythema associated with amethocaine occurred in one
      patient and slight itching in two patients. No other adverse features were
      evident.

PMID- 7640130
TI  - Comparison of duration of neuromuscular blocking effect of atracurium and
      vecuronium in young and elderly patients.
AB  - In a controlled, randomized study, we evaluated duration of neuromuscular block
      in 80 patients undergoing routine abdominal surgery. Forty patients were aged 18
      50 yr (control group) and 40 patients were more than 65 yr (elderly group). All
      patients had normal plasma creatinine concentrations. After induction of
      anaesthesia, patients were allocated randomly to receive either atracurium 0.5 mg
      kg-1 or vecuronium 0.1 mg kg-1 to facilitate tracheal intubation. Monitoring of
      the evoked response of the adductor pollicis muscle to supramaximal single twitch
      ulnar nerve stimulation every 10 s was performed and measured with a strain
      gauge. Repeat doses of atracurium 0.1 mg kg-1 or vecuronium 0.02 mg kg-1 were
      administered when the adductor pollicis response recovered to 25% of the control
      twitch height. We found that the duration of action of the initial dose of
      atracurium was similar in the control and elderly groups, and it did not vary
      after repeated doses. However, the initial dose of vecuronium caused a
      significantly longer period of clinical block in the elderly group compared with
      the controls, and the duration of action of repeated doses was longer in the
      elderly group. We conclude that as there is a risk of prolonged effect of
      vecuronium in the elderly, monitoring of neuromuscular function is recommended in
      this group. Alternatively, atracurium should be preferred for prolonged surgery
      in elderly patients.

PMID- 7640131
TI  - Effect of different volatile anaesthetics on suxamethonium-induced jaw muscle
      contracture in rats.
AB  - Previous work has demonstrated that the interaction of hyperthermia and halothane
      may greatly increase the jaw muscle contracture produced by suxamethonium. We
      have compared the interaction of temperature and suxamethonium in the presence of
      halothane with the suxamethonium/temperature interaction of two other volatile
      anaesthetics, isoflurane and desflurane. Rats were anaesthetized with 1.35 MAC of
      halothane, isoflurane or desflurane. The jaw area was heated to 36-41 degrees C
      by a heating lamp while rectal temperature was maintained at 37 degrees C.
      Isometric tension was recorded from the jaw muscles. Suxamethonium 750 micrograms
      kg-1 i.v. induced a transient jaw muscle contracture (JMC) during halothane,
      isoflurane and desflurane anaesthesia. JMC exhibited significant dependence on
      jaw muscle temperature with all three volatile anaesthetics. Increasing the
      temperature of the jaw area from 37 degrees C to 41 degrees C increased JMC 8.7
      fold with halothane, 8.8-fold with isoflurane and 3.1-fold with desflurane. The
      difference between halothane and desflurane was significant. While suxamethonium
      induced JMC was dependent on temperature for all three volatile anaesthetic, the
      temperature dependence appeared to be less with desflurane.

PMID- 7640132
TI  - Relationship of peak flow rate and peak velocity time during voluntary coughing.
AB  - The differences in phonation between men and women are thought to occur from
      anatomical differences in the larynx. However, it is not known if there are any
      differences in cough dynamics between the sexes. We investigated this by asking
      100 healthy, non-smoking adults (50 male) to perform a voluntary cough into a
      tussometer. Each volunteer coughed at four different lung volumes, ranging from
      total lung capacity to functional residual capacity. There was a positive
      correlation between peak velocity time and cough peak flow rate in both males (r
      = 0.73, P < 0.001) and females (r = 0.78, P < 0.001). Multiple regression
      analysis showed that height (P < 0.05) and sex (P < 0.001) were significant
      determinants of the relationship between peak flow rate and peak velocity time.
      In a height-matched subgroup, sex differences remained significant (P < 0.05).
      This may be related to anatomical differences in laryngeal structure and may have
      implications when using tussometry to assess laryngeal function.

PMID- 7640133
TI  - Auditory evoked responses and near infrared spectroscopy during cardiac arrest.
AB  - We describe a patient who had a cardiac arrest during anaesthesia, in whom
      regional cerebral oxygen saturation was being measured by near infrared
      spectroscopy and the auditory evoked responses (AER) were being recorded. Both of
      these monitors provided useful information on cerebral oxygenation during cardiac
      arrest. Changes in the AER as the result of either reduced circulation or
      hypothermia are similar, and should these two situations occur simultaneously
      there could be difficulty in the interpretation of the AER.

PMID- 7640134
TI  - Use of the Hayek oscillator in a case of failed fibreoptic intubation.
AB  - We describe the management of a patient with predicted difficult tracheal
      intubation after failed awake fibreoptic intubation. Anaesthesia was induced with
      propofol and ventilation controlled by means of the Hayek oscillator, a high
      frequency cuirass ventilator, without tracheal intubation. The patient underwent
      uneventful laser debulking of his massive pharyngeal tumour to establish a clear
      airway.

PMID- 7640135
TI  - Removal of lumbar extradural catheters.

PMID- 7640136
TI  - Prevention of venous air embolism: are humans like sheep?

PMID- 7640137
TI  - Comparison of sevoflurane with halothane: statistically valid?

PMID- 7640138
TI  - Rechargeable Optima laryngoscopes.

PMID- 7640139
TI  - Drugs, money and society.

PMID- 7640140
TI  - Comparison of non-invasive methods for the assessment of haemodynamic drug
      effects in healthy male and female volunteers: sex differences in cardiovascular
      responsiveness.
AB  - 1. The study was performed to determine the sensitivity and short-term and day-to
      day variability of a novel technique based on laser interferometry of ocular
      fundus pulsations and of non-invasive methods for the quantification of
      haemodynamic drug effects. An additional aim was to assess sex differences in
      haemodynamic responsiveness to cardiovascular drugs in male and female healthy
      volunteers. 2. Ten males and nine females (age range 20-33 years) were studied in
      a double-blind, randomized, cross-over trial. Simultaneous measurements from
      systemic haemodynamics, laser interferometry of ocular fundus pulsations,
      systolic time intervals from mechanocardiography, a/b ratio from oxymetric
      fingerplethysmography and Doppler sonography of the radial artery were used to
      describe the haemodynamic effects of cumulative, stepwise increasing intravenous
      doses of phenylephrine, isoprenaline, sodium nitroprusside and of placebo. 3.
      Laser interferometry detected the isoprenaline-effects at the lowest dose level
      of 0.1 micrograms min-1 with a high signal-to-noise ratio. The reproducibility of
      measurements under baseline was high, no changes were observed after systemically
      effective doses of phenylephrine or sodium nitroprusside. Systolic time intervals
      were sensitive and specific for isoprenaline-induced effects, PEP and QS2c
      measurements had high reproducibility. Fingerplethysmography proved a sensitive
      measurement for the detection of the vasodilating effects of sodium
      nitroprusside, but was not specific, and showed low reproducibility. Measurements
      from Doppler sonography had lower reproducibility and sensitivity compared with
      the other applied methods. 4. There was a significant sex difference for several
      of the haemodynamic parameters under baseline conditions; however, the
      responsiveness to the drugs under study was not different, when drug effects were
      expressed as %-change from the baseline. 5. Laser interferometry is a valuable
      non-invasive, highly sensitive and specific approach for the detection of pulse
      pressure changes. A battery of non-invasive tests appears useful for the
      characterization of cardiovascular drugs. Gender differences may not pose a
      relevant problem for the study of acute haemodynamic effects of cardiovascular
      drugs.

PMID- 7640141
TI  - Comparison of the pharmacokinetics and pharmacodynamics of oral doses of
      perindopril in normotensive Chinese and Caucasian volunteers.
AB  - 1. The pharmacokinetics of perindopril and perindoprilat and the hormonal and
      haemodynamic responses following a single oral dose were studied in 12 Chinese
      and 10 Caucasian healthy, normotensive volunteers on two occasions. Perindopril
      was given on the first occasion as a 4 mg dose and then after at least 10 days as
      a weight-adjusted dose of 4 mg/70 kg. Plasma was sampled for assay of
      perindopril, perindoprilat, plasma renin activity (PRA), aldosterone, angiotensin
      I (AI) and ACE activity. Urine was collected for perindopril and perindoprilat
      assay. A radioimmunoassay technique was used to measure the prodrug and its
      active metabolite. 2. The time to maximum concentration (tmax) for perindopril
      was shorter for the Chinese group after the 4 mg dose (median 0.5, range 0.5-1.5
      h vs median 1.0, 0.5-1.5 h P < 0.05) and also tended to be shorter after the
      weight-adjusted dose (median 0.5, range 0.5-1.0 h vs median 1.0, range 0.5-3.0
      h). Cmax and AUC tended to be higher after the 4 mg dose in the Chinese group who
      had a lower body weight than the Caucasians. 3. The tmax of perindoprilat tended
      to be shorter for both doses and there was a tendency towards a higher Cmax after
      the 4 mg dose in the Chinese group but there was no statistically significant
      difference between the two groups. 4. There were no differences in the levels of
      PRA, plasma AI, plasma aldosterone or the degree of ACE-inhibition for either
      dose in the two ethnic groups. 5. Blood pressure was measured at intervals up to
      24 h post-dose in both the supine and standing positions. Perindopril reduced
      blood pressure acutely with respect to the pre-dose level with good tolerability
      in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7640142
TI  - The potentiation of adrenaline-induced in vitro platelet aggregation by ADP,
      collagen and serotonin and its inhibition by naftopidil and doxazosin in normal
      human subjects.
AB  - 1. Aggregation in platelet-rich plasma from normotensive men was induced by
      adrenaline (0.25-16 microM), ADP (0.25-16 microM), collagen (0.25-8 micrograms ml
      1) or serotonin (10 microM) alone, or by previously sub-threshold concentrations
      of adrenaline (0.03-1 microM) in combination with sub-threshold concentrations of
      serotonin (2.5 microM), ADP (0.5 microM) or collagen (0.125 micrograms ml-1). The
      effects of the alpha 1-adrenoceptor blockers naftopidil and doxazosin on platelet
      aggregation were investigated. 2. The dose-response curves for collagen and ADP
      were unaffected by either drug. However, naftopidil (40 microM) inhibited
      serotonin-induced platelet aggregation (23.9%, 95% confidence interval (CI) 10.7
      to 37.1%; P < 0.01) and caused a slight shift to the right of the adrenaline dose
      response curve with a mean increase in the EC50 value of 0.5 microM (95% CI 0.07
      to 0.93 microM; P < 0.05). Doxazosin had no effect on serotonin or adrenaline
      induced aggregation. 3. A marked potentiation of the aggregation induced by
      subthreshold concentrations of adrenaline resulted from the prior addition of low
      concentrations of ADP, collagen or serotonin. 4. These potentiated responses were
      inhibited in a dose-dependent manner by naftopidil and to a lesser extent
      doxazosin. The maximum inhibitions (%) produced by naftopidil (40 microM) on the
      responses of adrenaline potentiated by ADP were 58.3% (95% CI 36.8 to 79.8%; P <
      0.001), serotonin 58.9% (95% CI 40.0 to 77.8%; P < 0.001), and collagen 70.9%
      (95% CI 52.5 to 89.3%; P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7640143
TI  - Pharmacokinetics and pharmacodynamics of tucaresol, an antisickling agent, in
      healthy volunteers.
AB  - 1. Tucaresol is an orally administered antisickling agent which increases the
      oxygen affinity of haemoglobin. 2. The pharmacokinetics, effects on moderate
      graded exercise and psychometric performance of tucaresol were examined in a
      double-blind, placebo-controlled, parallel groups study in 12 healthy men. 3.
      Three doses of tucaresol were given at 48 h intervals intended to modify 15, 25
      and 32.5% of a subject's haemoglobin to a high affinity form (%MOD). 4. Mean peak
      %MOD was 34%. Mean Cmax values in plasma and erythrocytes were 81.4 and 1459
      micrograms ml-1, respectively. 5. Heart rate, compared with baseline, increased
      in the tucaresol group with the greatest changes at the highest %MOD and
      workload. There were no differences between groups in psychometric test
      performance. 6. Three volunteers on active drug developed fever, rash and tender
      cervical lymphadenopathy with onset 7-10 days from the start of dosing,
      suggesting an immune mechanism. 7. The acute increase in oxygen affinity with
      tucaresol is physiologically well-tolerated, but the utility of tucaresol in the
      management of sickle cell disease will depend on the identification of a dosing
      regimen with a lower incidence of drug allergy.

PMID- 7640144
TI  - The effects of pharmaceutical excipients on small intestinal transit.
AB  - 1. The effect of three iso-osmotic pharmaceutical excipient solutions on
      gastrointestinal transit were investigated in eight healthy male volunteers. Each
      subject received 200 ml radiolabelled purified water, or a 200 ml solution of
      sodium acid pyrophosphate ((SAPP) 1.1 g/200 ml), mannitol (2.264 g/200 ml) or
      sucrose (4.08 g/200 ml) in a four way cross over design. On each of the study
      days the volunteers also received five 6 mm diameter non-disintegrating tablets.
      Dual isotope gamma scintigraphy was used to assess the transit behaviour of the
      tablets and solutions. 2. There were no significant differences between the
      gastric emptying times of the four solution formulations. Rapid gastric emptying
      was observed in all cases (mean t 50% varied from 11-14 min). 3. Small intestinal
      transit (SIT) times for the SAPP and mannitol solutions were reduced by 39 and
      34%, respectively, when compared with the control solution (purified water = 240
      min; SAPP = 147 min; mannitol = 158 min). The 95% confidence limits for the mean
      differences in SIT time between the control and SAPP solutions was 39-94-149 min,
      and 40-82-124 min between the mannitol and the control. Intestinal transit for
      the sucrose solution was similar to that for the control solution (sucrose = 229
      min). 4. There were no significant differences in the transit times of the non
      disintegrating tablet preparations, when co-administered with each
      solution.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7640146
TI  - A comparative study of acute and subchronic effects of dothiepin, fluoxetine and
      placebo on psychomotor and actual driving performance.
AB  - 1. The acute and subchronic effects of dothiepin 75-150 mg and fluoxetine 20 mg
      on critical fusion frequency (CFF), sustained attention and actual driving
      performance were compared with those of placebo in a double-blind, cross-over
      study involving 18 healthy volunteers. Drugs and placebo were administered for 22
      days in evening doses. Fluoxetine doses were constant but dothiepin doses
      increased on the evening of day 8. Performance was assessed on days 1, 8 and 22
      of each treatment series. Subjective sleep parameters and possible side effects
      were recorded on visual analogue scales on alternate treatment days. 2. Dothiepin
      reduced sustained attention on day 1 by 6.7% (95% confidence interval (C1): -12.0
      to -1.3%) and CFF on day 22 by 1.1 (CI: -2.2 to -0.1) Hz. Fluoxetine reduced
      sustained attention days 1, 8 and 22 of treatment by 7.4, 6.7 and 6.5%
      respectively (CI: -11.3 to -3.6; -14.3 to -1.5 and -9.5 to -3.4). CFF decreased
      linearly over days during fluoxetine treatment and significantly differed from
      placebo on day 22 with 1.2 Hz (CI: -2.3 to -0.2). Neither drug significantly
      affected driving performance. Whilst receiving dothiepin, subjects complained of
      drowsiness on days 1-3 of treatment (mean rank 5.6; CI: 2.0 to 9.2) and slept 43
      min longer (CI: 8.2 to 76.2).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7640145
TI  - The effects of oral sumatriptan, a 5-HT1 receptor agonist, on circulating ACTH
      and cortisol concentrations in man.
AB  - 1. The effects of oral sumatriptan (50, 100 and 200 mg), a 5-HT1 receptor
      agonist, and placebo, on circulating adrenocorticotrophic hormone (ACTH) and
      cortisol concentrations were determined over 24 h after dosing, in 26 healthy
      male subjects. ACTH was measured by immunoradiometric assay and cortisol by
      radioimmunoassay. 2. After sumatriptan all subjects displayed a normal diurnal
      rhythm for circulating ACTH and cortisol compared with placebo. 3. There was a
      reduction in the trough circulating ACTH concentration over 0-4 h which was 18%
      with 100 mg (P = 0.002), and 25% with 200 mg (P < 0.001). The 5 h, post-prandial,
      peak ACTH concentration was reduced by 21% with 100 mg (P = 0.018) and by 20%
      with 200 mg (P = 0.024). The weighted mean ACTH over 24 h was reduced by 8% with
      100 mg (P = 0.029) and by 8% with 200 mg (P = 0.018). The nadir concentration of
      ACTH over the 24 h and the ACTH concentration 24 h after sumatriptan were not,
      however, significantly reduced. All results are compared with placebo. 4. There
      was a reduction in the trough circulating cortisol concentration over 0-4 h which
      was 15% with 50 mg (P = 0.015), 14% with 100 mg (P = 0.022) and 24% with 200 mg
      (P < 0.001). The 5 h, post-prandial, peak cortisol concentration was reduced by
      16% with 100 mg (P = 0.012) and by 15% with 200 mg (P = 0.017).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7640147
TI  - Sensation seeking amongst healthy volunteers participating in phase I clinical
      trials.
AB  - 1. Phase I clinical trials are usually carried out in healthy volunteers. In
      addition to economic gain, factors that may influence willingness to participate
      include scientific interest, curiosity and choice for risky activities. 2. We
      assessed the relationship between personality variables and volunteering for
      clinical pharmacology research. Two personality questionnaires, the Sensation
      Seeking Scale (SSS, form V) and the Eysenck Personality Questionnaire (EPQ), were
      administered to 48 male healthy university students who volunteered to
      participate in a phase I clinical trial and to 43 male university students who
      were not willing to participate in phase I clinical trials. General norm data
      were also used for the comparison of results. 3. When healthy volunteers were
      compared with unwilling subjects, significant differences were found in thrill
      and-adventure seeking (7.9 vs 6.7, P = 0.0034), experience seeking (6.4 vs 5.2, P
      = 0.0012), disinhibition (6.2 vs 4.3, P < 0.0001), boredom susceptibility (3.9 vs
      2.8, P = 0.0073), total sensation seeking trait (24.3 vs 19.0, P < 0.0001),
      extraversion (15.1 vs 13.3, P = 0.0490), and psychoticism (4.4 vs 3.5, P =
      0.0086). When healthy volunteers were compared with general norm data similar
      statistically significant differences were found in all these scales, except for
      boredom susceptibility and psychoticism. 4. The personality profile of healthy
      volunteers was characterized by a higher sensation seeking trait and extraversion
      as compared with individuals who were not willing to participate in phase I
      clinical trials and general norm data.

PMID- 7640148
TI  - Glutathione S-transferase mu genotype (GSTM1*0) in Alzheimer's patients with
      tacrine transaminitis.
AB  - 1. Tacrine (1,2,3,4-tetrahydro-9-aminoacridine) which is used in Alzheimer's
      disease, causes elevation of liver transaminases ('tacrine transaminitis') in 40
      50% of patients. This may be related to the formation of a chemically reactive
      metabolite from tacrine, which can be detoxified in vitro by glutathione. 2.
      Glutathione-S-transferase mu (GSTM1), a detoxication enzyme, is polymorphically
      expressed being absent in about 50% of patients. Its role in the detoxication of
      the reactive metabolite of tacrine is not known. 3. The frequency of the enzyme
      deficiency (GSTM1*0) has been investigated in patients with tacrine transaminitis
      using polymerase chain reaction (PCR) to determine whether the GSTM1 status can
      be used as an absolute predictive factor for susceptibility to tacrine
      transaminitis. 4. The frequency of the GSTM1*0 genotype in patients with tacrine
      transaminitis (n = 33; 45.5%) was not significantly different from that in
      patients treated with tacrine without liver dysfunction (n = 37; 43%), and when
      compared with all the controls used in the study (n = 167; 56%). 5. The frequency
      of the GSTM1*0 genotype in patients with Alzheimer's disease (n = 79; 46%) was
      not significantly different from that in healthy volunteers (n = 121; 59.5%). 6.
      Our results indicate that the GSTM1 status cannot be used clinically to predict
      individual susceptibility to tacrine transaminitis, and that patients with the
      GSTM1*0 genotype are unlikely to have an increased risk of tacrine-induced liver
      damage. Furthermore, the GSTM1 status was not associated with Alzheimer's
      disease.

PMID- 7640149
TI  - Cytochrome P4502D6 genotype does not determine response to clozapine.
AB  - 1. The atypical antipsychotic drug clozapine, used in the treatment of resistant
      schizophrenia, is metabolized partly by the hepatic cytochrome P450 enzyme
      CYP2D6. Two phenotypes with respect to the activity of the enzyme are recognized
      (extensive metabolisers (EM) and poor metabolisers (PM)), resulting from allelic
      variation in the gene, CYP2D6. 2. Genotype was determined in 123 schizophrenic
      patients currently being treated with clozapine, in order to determine if EM or
      PM status influences response to this drug. Patients were divided into responders
      and non-responders using the Global Assessment Scale, and genotyped for the A and
      B poor metaboliser mutations by digesting PCR products with HpaII or BstNI. 3.
      Fifty-nine patients were heterozygous for allele B and for allele A. Eight
      patients were determined as poor metabolisers since they were homozygous either
      for A and B. Poor metabolisers were equally distributed between responders and
      nonresponders and no correlation between CYP2D6 alleles and response to clozapine
      was found. 4. The results are consistent with recent findings showing that
      CYP1A2, rather than CYP2D6, is the major enzyme responsible for the metabolism of
      clozapine.

PMID- 7640150
TI  - Identification of human CYP isoforms involved in the metabolism of propranolol
      enantiomers--N-desisopropylation is mediated mainly by CYP1A2.
AB  - 1. Studies using human liver microsomes and six recombinant human CYP isoforms
      (i.e. CYP1A2, 2A6, 2B6, 2D6, 2E1 and 3A4) were performed to identify the
      cytochrome P450 (CYP) isoform(s) involved in the ring 4-hydroxylation and side
      chain N-desisopropylation of propranolol enantiomers in humans. 2. alpha
      Naphthoflavone and 7-ethoxyresorufin (selective inhibitors of CYP1A1/2) inhibited
      the N-desisopropylation of R- and S-propranolol by human liver microsomes by 20
      and 40%, respectively, while quinidine (a selective inhibitor of CYP2D6)
      abolished the 4-hydroxylation of both propranolol enantiomers almost completely.
      In contrast, sulphaphenazole (CYP2C8/9 inhibitor), S-mephenytoin (CYP2C19
      inhibitor), troleandomycin (CYP3A3/4 inhibitor) and diethyldithiocarbamate
      (CYP2E1 inhibitor) elicited only weak inhibitory effects on propranolol
      metabolism via the two measured metabolic pathways. 3. Significant (P < 0.01)
      correlations were observed between the microsomal N-desisopropylation of both
      propranolol enantiomers and that for the O-deethylation of phenacetin among the
      11 different human liver microsome samples (r = 0.98 and 0.77 for R- and S
      propranolol, respectively). A marginally significant (r = 0.60, P congruent to
      0.05) correlation was also observed between N-desisopropylation of S-, but not of
      R-propranolol and the 4'-hydroxylation of S-mephenytoin. No significant
      correlations were observed between the N-desisopropylation of propranolol
      enantiomers and the 2-hydroxylation of desipramine, the hydroxylation of
      tolbutamide or the 6 beta-hydroxylation of testosterone. 4. Significant (P <
      0.01) correlations were observed between the microsomal 4-hydroxylation of R- and
      S-propranolol and the 2-hydroxylation of desipramine (r = 0.85 and 0.98,
      respectively). A weak (r = 0.66), albeit significant (P < 0.05) correlation was
      observed between the 4-hydroxylation of R-, but not of S-propranolol and the
      hydroxylation of tolbutamide. No significant correlations were observed between
      the 4-hydroxylation of propranolol enantiomers and the oxidation of other
      substrates for CYP1A2, 2C19, and 3A3/4. 5. Recombinant human CYP1A2 and CYP2D6
      exhibited comparable catalytic activity with respect to the N-desisopropylation
      of both propranolol enantiomers; only expressed CYP2D6 exhibited a marked
      catalytic activity with respect to the 4-hydroxylation of both propranolol
      enantiomers.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7640152
TI  - The role of S-mephenytoin hydroxylase (CYP2C19) in the metabolism of the
      antimalarial biguanides.
AB  - The effects of the CYP2C19 substrates, mephenytoin, methsuximide and
      mephobarbitone on the metabolism of proguanil and chlorproguanil by human liver
      microsomes were studied. All of the CYP2C19 substrates significantly inhibited (P
      < 0.05) the formation of both cycloguanil and chlorcycloguanil from their parent
      compounds. In the presence of mephenytoin (50 and 100 microM) the extent of
      proguanil cyclisation was decreased by 66% and 67% whilst the cyclisation of
      chlorproguanil was decreased by 51% and 70%, respectively. Methsuximide (50 and
      100 microM) inhibited cycloguanil formation by 68% and 77% and chlorcycloguanil
      formation by 43% and 58%, respectively. In the presence of mephobarbitone (50 and
      100 microM) the cyclisation of proguanil and chlorproguanil to their active
      metabolites was reduced by 24% and 42% and 48% and 63%, respectively. In
      addition, proguanil and chlorproguanil were shown to be mutual competitive
      inhibitors of metabolism to their triazine metabolites. In the presence of
      proguanil (50 and 100 microM) the Km value for chlorcycloguanil production was
      increased by 118% and 200%, respectively, with little change in Vmax. Similarly,
      chorproguanil (50 microM) increased the Km for the in vitro cyclisation of
      proguanil by 50% with no alteration in Vmax. These data suggest that both
      chlorproguanil and proguanil are metabolised in vitro by mephenytoin hydroxylase,
      CYP2C19.

PMID- 7640151
TI  - Imipramine metabolism in relation to the sparteine and mephenytoin oxidation
      polymorphisms--a population study.
AB  - 1. Sparteine and mephenytoin phenotyping tests were carried out in 327 healthy
      Danish subjects. Two weeks later each subject took 25 mg imipramine followed by
      urine collection for 24 h. The urinary content of imipramine, desipramine, 2
      hydroxy-imipramine and 2-hydroxy-desipramine was assayed by h.p.l.c. 2. The
      medians of the hydroxylation ratios (i.e. 2-hydroxy-metabolite over parent
      compound) were 6 to 14 times higher in 300 extensive metabolizers of sparteine
      (EMs) as compared with 27 poor metabolizers (PMs), but none of the ratios
      separated the two phenotypes completely. 3. There were 324 EM of mephenytoin
      (EMM) and three PM (PMM) in the sample. The demethylation ratios between
      desipramine, 2-hydroxy-desipramine and their corresponding tertiary amines showed
      statistically significant correlations with the mephenytoin S/R isomer ratio
      (Spearman's rs: -0.20 and -0.27, P < 0.05). 4. The demethylation ratios were
      higher in 80 smokers than in 245 non-smokers. This indicates that CYP1A2, which
      is induced by cigarette smoking, also catalyzes the N-demethylation of
      imipramine. 5. CYP2D6 genotyping was carried out by PCR in 325 of the subjects,
      and the D6-wt allele was amplified in 298 EMs, meaning that they were genotyped
      correctly. One PMs was D6-wt/D6-B, another PMs had the genotype D6-wt/ and hence
      both were misclassified as EMs. The remaining 25 PMs were D6-A/D6-B (n = 5), D6
      B/ (n = 18) or D6-D/D6-D (no PCR amplification, n = 2).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7640153
TI  - The pharmacokinetics of teniloxazine in healthy subjects and patients with
      hepatic cirrhosis.
AB  - The single-dose and steady-state pharmacokinetics of teniloxazine, an
      investigational drug with antidepressant and anti-anoxic properties, were
      compared in 12 healthy volunteers and 12 cirrhotic patients, following oral
      administration of 80 mg teniloxazine maleate every 12 h for 7 days. In healthy
      volunteers, an increase in oral clearance, CLo (from a mean (s.d.) value of 14.6
      (3.9) to 18.0 (6.6) ml min-1 kg-1; mean % ratio between the two values (95% CI),
      123 (94-151)) and a significant shortening of t 1/2 (from 6.2 (2.7) to 4.8 (1.4)
      h; mean % ratio (95% CI), 78 (58-98)) were observed upon repeated administration,
      suggesting autoinduction of teniloxazine metabolism. In cirrhotic patients, the
      pharmacokinetic parameters of teniloxazine remained essentially invariant with
      time. Compared with normal subjects, CLo was about halved in cirrhotic patients,
      whereas t 1/2 was more than doubled. As a consequence of these modifications, the
      multiple-dose regimen resulted in a two-fold mean drug accumulation in cirrhotic
      patients, compared with virtually no accumulation in healthy volunteers. Although
      no adverse events were noted in either study group, it is suggested that
      maintenance doses for patients with liver dysfunction should initially be at the
      lower end of the therapeutic range.

PMID- 7640154
TI  - Absorption of clonazepam after intranasal and buccal administration.
AB  - Serum concentrations of clonazepam after intranasal, buccal and intravenous
      administration were compared in a cross-over study in seven healthy male
      volunteers. Each subject received a 1.0 mg dose of clonazepam intranasally and
      buccally and 0.5 mg intravenously. A Cmax of 6.3 +/- 1.0 ng ml-1 (mean; +/- s.d.)
      was measured 17.5 min (median) (range 15-20 min) after intranasal administration.
      A second peak (4.6 +/- 1.3 ng ml-1) caused by oral absorption was seen after 1.7
      h (range 0.7-3.0 h). After buccal administration a Cmax of 6.0 +/- 3.0 ng ml-1
      was measured after 50 min (range 30-90 min) with a second peak of 6.5 +/- 2.5 ng
      ml-1 after 3.0 h (range 2.0-4.0 h). Two minutes after i.v. injection of 0.5 mg
      clonazepam the serum concentration was 27 +/- 18 ng ml-1. It is concluded that
      intranasal clonazepam is an alternative to buccal administration. However, the
      Cmax of clonazepam after intranasal administration is not high enough to
      recommend the intranasal route as an alternative to intravenous injection.

PMID- 7640155
TI  - Pharmacokinetics of ifosfamide and its enantiomers following a single 1 h
      intravenous infusion of the racemate in patients with small cell lung carcinoma.
AB  - Ifosfamide is a chiral pro-drug which is administered clinically in its racemic
      form. Serum concentrations of rac-ifosfamide and its enantiomers were measured in
      12 patients with lung carcinoma following a mean (+/- s.d.) intravenous dose of
      4.2 (0.83) g infused over 1 h. The mean (+/- s.d.) volumes of distribution (VSS)
      of rac, (R)- and (S)-ifosfamide were 0.61 (0.17), 0.60 (0.16) and 0.61 (0.19) l
      kg-1, respectively. The mean (+/- s.d.) half-lives and clearances were 6.57
      (1.69), 7.12 (1.92) and 5.98 (1.52) h and 0.065 (0.013), 0.060 (0.013) and 0.072
      (0.014) l h-1 kg-1 for rac, (R)- and (S)-ifosfamide, respectively. The half-life
      of (S)-ifosfamide was significantly (P < 0.001) shorter than that of (R)
      ifosfamide and it had a significantly higher clearance (P < 0.001). There was no
      significant difference in the volumes of distribution of the enantiomers. The
      clinical significance of the faster elimination of (S)-ifosfamide is not known.

PMID- 7640157
TI  - The effect of amoxycillin on salivary nitrite concentrations: an important
      mechanism of adverse reactions?
AB  - Broad spectrum antibiotics are known to predispose towards oral candidiasis and
      gastroenteritis. Oral nitrite synthesis by commensal bacteria may be important in
      protecting the mouth and lower intestine from pathogenic organisms, including
      Candida albicans. The effect of 2 days administration of the broad spectrum
      antibiotic amoxycillin on salivary nitrite concentration, following a 200 mg
      potassium nitrate oral load, was studied in 10 healthy volunteers. The Cmax fell
      by 40% and the AUC was reduced by 1227 microM h (43%, 95% CI 273, 2181, P <
      0.006) in the antibiotic treated group when compared with control. These findings
      suggest that destruction of nitrate reductase containing bacteria in the mouth by
      antibiotics may explain an increased incidence of infection with Candida and
      other pathogens.

PMID- 7640156
TI  - Sulphasalazine inhibition of thiopurine methyltransferase: possible mechanism for
      interaction with 6-mercaptopurine and azathioprine.
AB  - Thiopurine drugs are used in the treatment of inflammatory bowel disease--as are
      sulphasalazine and its metabolite 5-aminosalicylic acid (ASA). S-Methylation
      catalyzed by thiopurine methyltransferase (TPMT) is a major pathway in the
      metabolism of thiopurines. The hypothesis was tested that TPMT might be inhibited
      by sulphasalazine or isomers of ASA. Sulphasalazine as well as 3-, 4- and 5-ASA
      inhibited recombinant human TPMT, with IC50 values of 78, 99, 2600 and 1240
      microM, respectively. Kinetic studies demonstrated that the inhibition of TPMT by
      sulphasalazine and ASA isomers was non-competitive with regard to the thiopurine
      substrate, 6-MP, and was uncompetitive with regard to the methyl donor for the
      reaction, S-adenosyl-L-methionine. Our observations raise the possibility of a
      clinically significant drug-drug interaction in patients treated simultaneously
      with sulphasalazine and thiopurine drugs.

PMID- 7640158
TI  - A retrospective analysis of the prevalence of HIV seropositivity and its
      demographics in the normal healthy volunteer population of a phase-I clinical
      drug study unit.

PMID- 7640159
TI  - The alpha spending function approach to interim data analyses.

PMID- 7640160
TI  - A review of tree-based prognostic models.

PMID- 7640161
TI  - Decision analysis and Bayesian methods in clinical trials.

PMID- 7640162
TI  - A Bayesian model for evaluating specificity of treatment effects in clinical
      trials.

PMID- 7640163
TI  - The exact analysis of contingency tables in medical research.

PMID- 7640164
TI  - Stratified-adjusted versus unstratified assessment of sample size and power for
      analyses of proportions.

PMID- 7640165
TI  - Quality-of-life assessment in clinical trials.

PMID- 7640166
TI  - Issues in the design and analysis of AIDS clinical trials.

PMID- 7640167
TI  - Recent developments in the design of phase II clinical trials.

PMID- 7640168
TI  - Multivariate failure time data.

PMID- 7640169
TI  - Goodness-of-fit and diagnostics for proportional hazards regression models.

PMID- 7640170
TI  - Lack of metabolic racemisation of ropivacaine, determined by liquid
      chromatography using a chiral AGP column.
AB  - Ropivacaine hydrochloride monohydrate (ropivacaine) is a new local anaesthetic
      agent which is administered exclusively as the (-)-(S)-form. The aim of the study
      was to determine whether metabolic racemisation of (-)-(S)-ropivacaine occurs.
      This was tested in man, rat, dog, and sheep after different routes of
      administration. The enantiomers of ropivacaine and two of the major metabolites,
      3-hydroxy-ropivacaine and 2',6'-pipecoloxylidide (PPX), were determined in urine
      samples by liquid chromatography on a Chiral AGP column after liquid-liquid
      extraction. It was possible to detect < 1% of the (+)-(R)-enantiomer of both
      ropivacaine and the two major metabolites. In the samples examined, no trace of
      metabolic racemisation was observed. In pharmacokinetic, pharmacodynamic,
      toxicological, and metabolic studies, therefore, nonchiral assays are considered
      to be adequate.

PMID- 7640171
TI  - Stereochemical aspects of the hydration of trans-anethole epoxide in the rat.
AB  - Racemic trans-anethole epoxide [1-(4'-methoxyphenyl)-propane-1,2-oxide] was
      incubated with water, buffers, and rat liver microsomes and cytosol and the
      stereochemistry of the diols produced was determined by HPLC as their dicamphanyl
      esters. The diol metabolites were isolated by HPLC from the urine of rats
      administered [1'-14C] trans-anethole and their stereochemistry determined after
      derivatization to their camphanyl esters. The stereochemical course of the
      metabolism of trans-anethole by rat liver microsomes and cytosol is discussed.

PMID- 7640172
TI  - Stereoselective and species-dependent kinetics of reboxetine in mouse and rat.
AB  - Reboxetine, (RS)-2-[(RS)-alpha-(2-ethoxyphenoxy)benzyl]morpholine
      methanesulphonate, is a racemic compound and consists of a mixture of the (R,R)-
      and (S,S)-enantiomers. In this study, brain and plasma levels of both enantiomers
      were determined in mice and rats after oral administration of reboxetine at doses
      (1.1 mg/kg, mouse; 20 mg/kg, rat) twice the respective ED50 values in the
      antireserpine test. Plasma and brain concentrations of each enantiomer were
      measured up to 6 h postdosing using an HPLC method with fluorimetric detection
      after derivatization with a chiral agent (FLEC). In mice and rats, brain and
      plasma levels of the (R,R)-enantiomer were always higher than those of the (S,S)
      enantiomer. After normalization for dose, the mean AUC0-tz values of both the
      (R,R)- and (S,S)-enantiomers in mouse brain were about 23 and 32 times higher
      than in rat brain, respectively. In plasma, the corrected mean AUC0-tz values
      were about 5 (R,R) and 10 (S,S) times higher in mice than in rats. These results
      provide evidence for the higher bioavailability and/or lower clearance of both
      enantiomers in mice than in rats, and for a higher penetration of both
      enantiomers into mouse brain compared to rat brain.

PMID- 7640173
TI  - Enantioselective assay of beta-receptor antagonists present in microdialysis and
      plasma samples of rats.
AB  - The enantiomers of alprenolol, metoprolol, and propranolol have been separated on
      an enantioselective cellulase column and analysed using a fully automated HPLC
      system involving coupled column chromatography and fluorescence detection. The
      assays had sufficient selectivity and sensitivity to investigate the disposition
      of these beta 2-receptor antagonists in blood and brain extracellular fluid of
      rats. A cellulase column was used as the first column to separate the enantiomers
      giving separation factors between 2.9 and 4.3. After the separation, the
      enantiomers were trapped on two small precolumns by the use of a switching valve
      and were then introduced on an achiral C18 analytical column by eluting the small
      columns backward. The enantiomers in blood and brain tissue dialysates were
      analysed by direct injection of 8 microliters samples. The limit of quantitation
      was 0.025-0.4 micrograms/ml of the different enantiomers. Plasma samples were
      analysed after a simple extraction procedure. The intraassay precision of the
      lowest quality control plasma samples (0.2-0.8 micrograms rac-drug/ml) was 4-8%
      for the different enantiomers.

PMID- 7640174
TI  - Stereoselective hydrolysis of xenobiotic esters by different cell lines from rat
      liver and hepatoma and its application to chiral prodrugs for designated growth
      suppression of cancer cells.
AB  - Stereoselectivity in the hydrolysis of racemic ethyl 2-phenylacetate derivatives
      by cultured cells of noncancerous cell lines from rat liver (BRL, BRL 3A, Clone
      9, and ARLJ301-3), spontaneously or oncogene transformed rat liver cell lines
      (ARLJ301-3TR1, Anr4, Anr9-1, and Anr13-1), and cancer cell lines from rat
      hepatoma (H4-II-E, McARH7777, and MH1C1) and sarcoma (XC) was studied. A strong
      (R)-enantiomer preference was found in the hydrolysis of ethyl 2-hydroxy-(2c) and
      2-methoxy-2-phenylacetate (3c) by the noncancerous and oncogene-transformed cells
      and an (S)-enantiomer preference for ethyl N-acylphenylalaninates with all the
      present cell lines. These inclinations were, however, not recognized with ethyl 2
      methoxy-2-phenylpropanoate and ethyl N-difluoroacetyl- or N
      trifluoroacetylphenylalaninate. Moreover, the R preference for 3c was reversed in
      the reaction by hepatoma cells. Thus, the stereoselectivity is influenced by both
      structure of acyl group and species of cell lines. The hepatoma cells were
      considerably different from the noncancerous or oncogene-transformed cells in
      stereoselectivity. This fact was consistent with the order of colony formation in
      soft agar cultures (index of malignancy) and the resemblance in actively stained
      esterase patterns in gel electrophoresis. The stereoselective hydrolysis leads to
      cell-specific activation of anticancer prodrugs. This has been confirmed for the
      first time by the stereoselectivity of Anr4 and H4-II-E cells in the hydrolysis
      of a chiral mustard ester, bis(2-chloroethyl)aminophenyl 2-methoxy-2
      phenylacetate (14) and by the difference of IC50 values of (R)- and (S)-14
      against the two cell lines.

PMID- 7640175
TI  - Elevated tumor necrosis factor-alpha in association with severe anemia in human
      immunodeficiency virus infection and Mycobacterium avium intracellulare
      infection.
AB  - Mycobacterium avium intracellulare (MAI) infection is a serious opportunistic
      infection that occurs in children with human immunodeficiency virus (HIV)
      infection. In MAI the hematologic system is profoundly affected. In the present
      study the hematologic manifestations of MAI in 37 HIV-infected infants and
      children were reviewed. Anemia was the predominant feature in all patients, with
      severe anemia (hemoglobin < 6 g/dL) occurring in 7 of 34 (21%) patients. This was
      followed by leukopenia (79%), monocytosis (82%), thrombocytopenia (59%),
      leukoerythroblastic reaction (68%), and neutropenia (41%). Serum tumor necrosis
      factor (TNF)-alpha was markedly elevated in all patients with MAI with an X +/-
      SE of 702 +/- 182 pg/mL. There was an association between elevated TNF-alpha and
      anemia in these patients.

PMID- 7640176
TI  - Testicular function in adult males surviving childhood malignancy.
AB  - Testicular function was studied in 109 males aged 16 to 25 years surviving
      leukemia or solid tumors in childhood. The mean follow-up time was 10.3 years
      after diagnosis. Of the patients studied, 18 had received testicular
      radiotherapy, 35 central nervous system radiotherapy, and 3 total body
      radiotherapy. Twenty-one patients presented with incomplete puberty and 85
      presented with small testicles (< 20 mL). Of the 109 patients, 43 had elevated
      concentrations of serum follicle-stimulating hormone (FSH) or serum FSH and
      leutinizing hormone. Compared with survivors of solid tumors, the patients
      surviving acute lymphoblastic leukemia (ALL) had inferior testicular status. This
      was also the case even when those treated with testicular radiotherapy were
      excluded. Twenty-six patients were receiving testosterone substitution therapy at
      the time of the study; 25 of whom were survivors of ALL. The probability of
      normospermia was 50% if both testicular volume and serum FSH were within normal
      limits and 0% if they were abnormal. Of the 86 patients over 18 years of age, 16
      had evidence of normal testicular function. Of these 16, 8 patients had
      normospermia, only 1 of whom was a survivor of ALL. These findings suggest that
      ALL survivors have inferior testicular function compared with patients surviving
      solid tumors. Our findings confirm that testicular radiotherapy inevitably
      results in testicular damage, the degree of which is generally severe but
      variable in some individuals. We were unable to find an explanation for the
      individual tolerance to therapy, eg, age at diagnosis.

PMID- 7640177
TI  - Central venous catheter clots: incidence, clinical significance and catheter care
      in patients with hematologic malignancies.
AB  - In a 7-month period we studied 38 Hickman central venous catheters (CVCs)
      positioned in children with hematologic malignancies with the aim of evaluating
      the incidence and clinical impact of CVC clots. Clots were found in 74% of the
      CVCs. Three methods of catheter care were developed for flushing the clotted
      CVCs: (a) use of a heparinized solution (400 IU/mL) on alternate days, (b) use of
      a heparinized solution (400 IU/mL) and saline solution containing urokinase
      (10,000 IU/mL) on alternate days, and (c) use of a saline solution containing
      urokinase (10,000 IU/mL) daily. Only method b decreased clot formation (33%
      success rate). There were no major mechanical complications in any of the CVCs
      with clots. Eighteen percent of patients with clots in their CVCs presented with
      CVC-related infections while no infective complications were observed in the
      patients without clots in their CVCs. In conclusion, CVC clots may predispose the
      patient to infections, which must be correctly treated.

PMID- 7640178
TI  - An effective salvage regimen with aclarubicin for daunorubicin-resistant acute
      non-lymphocytic leukemia in children.
AB  - We evaluated the efficacy and toxicity of aclarubicin for acute non-lymphocytic
      leukemia (ANLL) refractory to daunorubicin in childhood. Twenty-four patients
      were treated with aclarubicin and prednisolone with or without 6-mercaptopurine
      and behenoyl-cytosine arabinoside daily for 5 to 14 days. Of 21 evaluable
      patients, 14 (67%) responded: 12 obtained complete remission and 2 partial
      remission. The median time to reach complete remission was 37 days (range, 16 to
      60 days), and the median duration of complete remission was 5.5 months (range, 2
      to 41 months). The cumulative dose of anthracycline administered before the study
      was not considered significant for the response. The only major complication was
      severe bone marrow suppression; infectious episodes occurred in 14 patients (58%)
      and three died of sepsis and/or bleeding. The observed non-hematologic toxicities
      included hematuria, an elevation of serum amylase, nausea/vomiting, and angitis.
      In addition, one patient showed abnormal cardiac function. Aclarubicin is
      therefore considered a highly active drug for remission reinduction of previously
      treated children suffering from ANLL with an acceptable toxicity.

PMID- 7640179
TI  - A PC database to facilitate treatment of pediatric hematology/oncology patients.
AB  - In an effort to simplify chemotherapy dose calculations and reduce the incidence
      of medication errors, a commercially available, general database management
      program was used to aid in the management of an active pediatric
      hematology/oncology service. The software was customized to include all
      medications used by the specialty practice, as well as some used in a general
      pediatric setting. After entering a patient's height and weight, the database
      rapidly computes and immediately displays the patient's surface area, appropriate
      intravenous fluid rates, and doses of antibiotic, chemotherapeutic, and other
      drugs. No prior computer expertise is required to run the program, which can be
      used easily by physicians and nurses. A database program similar to this can be
      implemented and customized easily for any hematology/oncology practice, and can
      facilitate patient care by reducing both the time and effort needed to order
      medications as well as the number of medication errors.

PMID- 7640180
TI  - Advanced nasopharyngeal carcinoma in the young: The Northern Israel Oncology
      Center experience, 1973-1991.
AB  - Between 1973 and 1991, 10 patients with locally advanced [stages III and IV]
      nasopharyngeal carcinoma were treated at the Northern Israel Oncology Center. All
      patients were treated with wide-field irradiation to the primary tumor, including
      the base of skull, neck, and supraclavicular region. After 1984, 6 patients also
      received cisplatin/5FU-based chemotherapy prior to radiotherapy and 1 patient
      received it after radiotherapy. All the patients who received chemotherapy are
      alive with no evidence of disease, for a mean disease-free survival of 96 months
      (range, 77 to 108 months), and no serious therapy-related late side-effects have
      been noted, except in one patient. We conclude that adjuvant chemotherapy may be
      effective in improving outcome, but only randomized prospective studies can
      evaluate its exact role.

PMID- 7640181
TI  - Burkitt's lymphoma: a case file study of 160 patients treated in Queen Elizabeth
      Central Hospital from 1988 to 1992.
AB  - From 1988 to 1992 160 children with clinically or pathologically proven Burkitt's
      lymphoma were seen and treated in Queen Elizabeth Central Hospital in Blantyre,
      Malawi. We present the epidemiologic features, the results of staging using
      ultrasonography, fine needle aspiration biopsy, and the different treatment
      regimens used. Lack of resources made it extremely difficult to provide the
      necessary high level of care for these children or to carry out a proper study in
      the management of this fascinating disease.

PMID- 7640182
TI  - Severe lactic acidosis and renal involvement in a patient with relapsed Burkitt's
      lymphoma.
AB  - We describe an 8-year-old patient with relapsed Burkitt's lymphoma who developed
      complex metabolic problems, including renal diabetes insipidus and severe lactic
      acidosis. The lactic acidosis responded temporarily to chemo- and radiotherapy
      but not to bicarbonate or thiamine administration. These metabolic changes were
      most likely due to the lymphomatous infiltration of the kidneys. Severe lactic
      acidosis, without evidence of thiamine deficiency, seems to be a very rare event
      in children with cancer.

PMID- 7640183
TI  - Prolonged remission induced by cyclosporine in a patient with familial
      thrombocytopenia and enteropathy.
AB  - A 21-year-old patient, since the age of 16, presented a familial type of chronic
      autoimmune thrombocytopenia that responded only partially to various types of
      immunosuppressive treatment. His prolonged survival, compared to his decreased
      siblings, was complicated by the appearance of a severe enteropathy. High doses
      of corticosteroids induced a type 1 diabetes as a major side effect. The
      introduction of cyclosporine resulted in both a continuous complete clinical
      remission and a partial hematological remission and allowed the discontinuation
      of all other medication for 18 months. In uncommon complex autoimmune disease,
      cyclosporine may represent a safe and effective alternate therapy when other
      immunosuppressive agents have failed.

PMID- 7640184
TI  - Listeria septicemia complicating bone marrow transplantation for Diamond-Blackfan
      syndrome.
AB  - Infection with Listeria monocytogenes is uncommon in patients receiving cytotoxic
      chemotherapy, and is even rarer among recipients of bone marrow transplantation.
      Hemosiderosis, either idiopathic or caused by transfusion, appears to be another
      risk factor. We report a 3-year-old Chinese girl with transfusion-dependent
      Diamond-Blackfan syndrome who had L. monocytogenes septicemia when she received
      an allogeneic bone marrow transplantation. She was treated successfully with
      intravenous ampicillin. Our case adds to the clinical evidence that patients with
      iron overload are susceptible to listeriosis, particularly when they are
      immunocompromised and do not receive iron-chelation treatment.

PMID- 7640185
TI  - Childhood leukemia is still a deadly disease in Yaounde, Cameroon: a report of 14
      cases.
AB  - In the Pediatric Unit of the University Teaching Hospital Center of Yaounde, 58
      of 2,900 (2%) hospitalized children aged 0 to 15 years who had a malignancy were
      studied. Fourteen (24.1%) had acute leukemia based on morphologic and
      cytochemical studies. Acute lymphoblastic leukemia was encountered in 11 of these
      patients (78.6%). The male to female ratio was 1.3 to 1. Nine of the 11 children
      (64.3%) were 5 years of age or younger. Eleven (78.6%) died of disease
      progression and its complications.

PMID- 7640186
TI  - Dysgerminoma in mother and daughter: use of lactate dehydrogenase as a tumor
      marker in the child.
AB  - A 7-year-old girl presented with an extragonadal dysgerminoma arising from the
      pelvis. Her mother had been treated for a histologically identical pituitary
      tumor 3 years previously. The child's serum lactate dehydrogenase (LDH) level was
      markedly elevated at presentation and fell as the tumor responded to treatment.
      The potential use of LDH as a marker for gonadal dysgerminoma is well documented,
      but raised LDH in association with primary extragonadal dysgerminoma has not been
      described previously. In addition, this is the first report of extragonadal
      dysgerminoma occurring in female relatives.

PMID- 7640188
TI  - Renal cell carcinoma in childhood: a case report.

PMID- 7640189
TI  - Eosinophilic vasculitis syndrome: recurrent cutaneous eosinophilic necrotizing
      vasculitis.
AB  - We recently identified a syndrome of recurrent cutaneous eosinophilic vasculitis
      in three patients. These patients had in common widespread pruritic,
      erythematous, purpuric papules and angioedema of face and hands associated with
      peripheral blood eosinophilia. Eight skin biopsies from these three patients all
      showed necrotizing vasculitis of the small vessels of the skin, with exclusively
      eosinophilic infiltration and minimal or no leukocytoclasis. The disease followed
      a chronic course, with recurrent, itchy, swelling skin lesions and without
      evidence of systemic involvement over observation periods of 3, 17, and 23 years.
      The skin lesions responded promptly to systemic steroid treatment, but two
      patients required maintenance doses for control of the disease.
      Immunofluorescence studies showed marked deposition of the cytotoxic eosinophil
      granule major basic protein in the affected vessel walls. Eosinophil-active
      cytokine IL-5 was detected in the serum of one patient. Expression of the
      vascular cell adhesion molecule-1 for eosinophil adherence was detected on the
      endothelium of the affected vessels. Because this disease showed distinctive
      clinical manifestations and characteristic histopathological features, we believe
      it is a distinct entity and should be distinguished from other types of
      vasculitis.

PMID- 7640190
TI  - Epidermal nevus syndromes.
AB  - A clinical entity called "the epidermal nevus syndrome" does not exist. Rather,
      there are various epidermal nevus syndromes that can be distinguished by
      clinical, histopathological, and genetic criteria. In this review, five distinct
      epidermal nevus syndromes, recognizable by different types of associated
      epithelial nevi, are described. The Schimmelpenning syndrome is characterized by
      a sebaceous nevus associated with cerebral anomalies, coloboma, and lipodermoid
      of the conjunctiva. By contrast, cataracts are a prominent feature of the nevus
      comedonicus syndrome. The pigmented hairy epidermal nevus syndrome includes
      Becker nevus, ipsilateral hypoplasia of the breast, and skeletal defects such as
      scoliosis. In the Proteus syndrome, the associated epidermal nevus is of a flat,
      velvety, nonorganoid type. The CHILD syndrome occurs almost exclusively in girls.
      The associated CHILD nevus shows unique features such as a diffuse form of
      lateralization, ptychotropism, and microscopic changes of verruciform xanthoma.
      The five epidermal nevus syndromes differ in their genetic basis. The
      Schimmelpenning and nevus comedonicus syndromes are most likely nonhereditary
      traits. By contrast, the pigmented hairy epidermal nevus syndrome and the Proteus
      syndrome may be explained by paradominant inheritance. The CHILD syndrome is
      caused by an X-linked dominant mutation exerting a lethal effect on male embryos.
      A correct diagnosis of these phenotypes is important for both recognition and
      treatment of associated anomalies as well as for genetic counseling.

PMID- 7640187
TI  - Primary pelvic neuroblastoma with central nervous system metastases.
AB  - Secondary intracranial neuroblastoma is an extremely rare site of metastasis from
      primary extracranial disease. Direct parenchymal involvement of the neuraxis
      without disease involving the overlying bone, dura, or venous sinuses is even
      rarer. We report a case of pelvic neuroblastoma with cerebral and cerebellar
      metastasis and communicating hydrocephalus, probably caused by diffuse
      leptomeningeal involvement. Clumps of neuroblastoma cells were seen in the
      cerebrospinal fluid (CSF). The CSF pathway was the probable route for neuraxis
      dissemination.

PMID- 7640191
TI  - Hypereosinophilic syndrome.
AB  - The hypereosinophilic syndrome is a multisystem syndrome characterized by
      peripheral blood eosinophilia and eosinophil infiltration of bone marrow, heart,
      and other organs. The syndrome is associated with cardiac, hematological,
      pulmonary, neurological, and cutaneous involvement and, if untreated, has a high
      fatality rate. Criteria for the diagnosis of hypereosinophilic syndrome include
      (1) peripheral blood eosinophilia with eosinophil counts greater than
      1,500/microL for at least 6 months; (2) no evidence of parasitic, allergic, or
      other known causes of eosinophilia; and (3) presumptive signs and symptoms of
      multiple organ involvement. Cutaneous manifestations occur commonly but are not
      diagnostic either clinically or histologically, although the presence of
      angioedema is a favorable prognostic sign. Because eosinophils are thought to
      mediate important pathogenic effects, treatment is aimed at controlling
      peripheral blood eosinophilia.

PMID- 7640192
TI  - Jadassohn-Lewandowski syndrome (pachyonychia congenita).
AB  - Pachyonychia congenita is an uncommon autosomal dominant disorder with variable
      expression. Symmetrical nail hypertrophy, present in nearly all cases, is
      accompanied by dyskeratosis and dysplasia of other ectodermal tissues. This
      article reviews the genetics, clinical manifestations, histopathology, and
      treatment of pachyonychia congenita. Many clinical features have been reported in
      association with this syndrome. From a review of the literature, we propose
      criteria for the diagnosis of pachyonychia congenita using the more important of
      these clinical manifestations.

PMID- 7640193
TI  - Melkersson-Rosenthal syndrome.
AB  - Melkersson-Rosenthal syndrome is a triad of recurrent orofacial swelling,
      relapsing facial paralysis, and fissured tongue. However, the classic triad is
      not frequently seen in its complete form. Monosymptomatic and oligosymptomatic
      forms are more common. The histological findings of sarcoid-like granuloma in
      skin or mucosal biopsy specimens support the diagnosis. The course is chronic but
      benign. Treatment is difficult, but intralesional or systemic corticosteroids may
      be helpful.

PMID- 7640195
TI  - Olmsted syndrome.
AB  - Nine cases of Olmsted syndrome have been reported in the world literature. In
      this syndrome, keratoderma usually starts during infancy on the palms and soles
      when the baby starts to use the feet for walking and the hands for grasping.
      Within weeks or months, there is progressive spread of solid, symmetrical, thick
      hyperkeratotic keratoderma to both palms and soles, surrounded by erythematous
      margins. Contraction of fingers and deep fissuring of the feet are common
      complications. Symmetrical, yellow-brown hyperkeratotic plaques and papules are
      also observed around body orifices such as the mouth, nares, inguinal region, and
      perianal and gluteal areas. Other clinical manifestations have been reported,
      including diffuse alopecia, thin nails, leukokeratosis of the oral mucosa,
      onychodystrophy, hyperkeratotic linear streaks, exaggerated keratosis pilaris,
      and large verrucous plaques in the axillae. In the differential diagnosis, other
      keratoderma and hyperkeratotic syndromes should be considered.

PMID- 7640196
TI  - Palmoplantar keratoderma and associated syndromes.
AB  - This article focuses on the current state of knowledge concerning the
      characterization and classification of palmoplantar keratoderma and associated
      syndromes. In addition, therapeutic options are discussed. Exact diagnosis
      enables dermatologists to give patients accurate genetic counseling and may help
      to detect underlying defects or proneness to cancer. Furthermore, precise
      classification of this disease facilitates the use of the most efficient
      therapeutic modalities. Important criteria for the classification of palmoplantar
      keratoderma are the mode of transmission, age at onset, and distribution of the
      keratoderma. The disorder may be diffuse or focal; it may be restricted to the
      palms and soles or also involve the dorsal aspects of the hands and feet.
      Psoriatic-like lesions in other parts of the body may occur in certain variants.
      The association of other signs and symptoms may provide diagnostic clues.
      Ultrastructural investigation will show diagnostic features in some types of
      palmoplantar keratoderma, and biochemical analysis may be helpful in the
      classification of keratoderma. In the future, the most accurate diagnosis will be
      the identification of the genetic defect and its chromosomal localization.

PMID- 7640194
TI  - Noonan syndrome.
AB  - The Noonan syndrome is a rare disease characterized by dysmorphic facies, short
      stature, ear abnormalities, cryptorchidism, ocular abnormalities, cardiovascular
      anomalies, cubitus valgus, webbed neck, and cutaneous and hair abnormalities.
      Some 25% to 40% of patients have dermatologic abnormalities. Diagnosis is purely
      clinical, and intrauterine diagnosis is very important based on the presence of
      cystic hygroma and evidence of myocardial abnormalities. Treatment is
      symptomatic. Genetic counseling is necessary.

PMID- 7640197
TI  - POEMS syndrome.
AB  - The principal features of POEMS syndrome are osteosclerotic bone lesions,
      peripheral sensorimotor neuropathy, and elevated levels of a monoclonal protein
      in the serum or urine. Skin lesions are present in the majority of patients with
      POEMS syndrome. Diffuse hyperpigmentation is the most common cutaneous finding.
      Hemangiomas with histopathological features resembling renal glomeruli are the
      most specific skin lesions.

PMID- 7640198
TI  - Sneddon syndrome.
AB  - Sneddon syndrome--cerebrovascular lesions and livedo racemosa--is a distinctive
      and uncommon disorder delineated by Sneddon in 1965. The clinical hallmarks are
      generalized livedo racemosa and central nervous system ischemia. Cutaneous
      vascular changes begin with intimal endothelial proliferation and fibromucinous
      matrix formation, leading to obstruction and obliteration of the vessel. The
      disorder is slowly progressive. No effective treatment is available, but platelet
      inhibiting agents or newer antithrombotic agents may offer some hope in
      preventing or minimizing serious sequelae of this disease.

PMID- 7640199
TI  - Sweet syndrome: acute febrile neutrophilic dermatosis.
AB  - Sweet, in 1964, described a skin condition characterized by fever, leukocytosis,
      tender erythematous plaques, and, histopathologically, a predominantly
      neutrophilic dermal inflammation. However, other dermatologic conditions can
      present with similar clinical and histological features. Therefore, diagnostic
      criteria are important for the correct diagnosis. Use of systemic steroids is the
      treatment of choice for Sweet syndrome. A number of other medications can be
      useful at times, such as potassium iodide, dapsone, indomethacin, and colchicine.

PMID- 7640200
TI  - TORCH syndrome.
AB  - The original TORCH complex described clinically similar congenital infections
      caused by Toxoplasma gondii, rubella virus, cytomegalovirus, and herpes simplex
      virus, types 1 and 2. Cutaneous manifestations, including petechiae, purpura,
      jaundice, and dermal erythropoiesis, are commonly seen in toxoplasmosis, rubella,
      and cytomegalovirus infections. In herpes simplex virus infections, 80% of
      symptomatic infants show single or grouped cutaneous vesicles, oral ulcers, or
      conjunctivitis. Extracutaneous signs and symptoms are variable and can be severe.
      Significant clinical signs in congenital toxoplasmosis include diffuse
      intracerebral calcification, chorioretinitis, and microcephaly; congenital
      rubella can result in deafness, congenital heart disease, retinopathy, and brain
      calcification. Cytomegalic inclusion disease can include hepatomegaly,
      splenomegaly, paraventricular calcification, and intrauterine growth retardation.
      Localized or disseminated congenital herpes virus infection often involves the
      central nervous system and the eye. Diagnosis is confirmed by culture and
      identification of species-specific immunoglobulin M within the first 2 weeks of
      life. Histological examination contributes to the diagnosis in herpes simplex
      virus infection. Treatment for toxoplasmosis includes pyrimethamine with
      sulfadiazine or trisulfapyrimidine; congenital herpes simplex virus infection is
      treated with acyclovir. No specific therapy for congenital rubella or
      cytomegalovirus infections has been established, and so treatment is primarily
      supportive.

PMID- 7640201
TI  - Bazex syndrome: acrokeratosis paraneoplastica.
AB  - The focus of this article is acrokeratosis paraneoplastica, one of two disorders
      that have acquired the eponym Bazex syndrome. To date, all of the patients
      reported in the literature have had an underlying neoplasm, most commonly
      squamous cell carcinoma of the upper aerodigestive tract. In this review of 113
      cases of acrokeratosis paraneoplastica (mean age, 61 years; 105 males, 8
      females), the psoriasiform lesions preceded the diagnosis of the associated
      malignancy in 73 (67%) of 109 patients, whereas the cutaneous manifestations
      followed the diagnosis of the neoplasm in only 16 (15%) of 109; in the remainder,
      the onset of the skin lesions and the diagnosis of the tumor occurred
      simultaneously. Therefore, awareness of the cutaneous signs of Bazex syndrome is
      of obvious importance to dermatologists. Evidence in favor of the paraneoplastic
      nature of this disease is as follows: in 81 (93%) of 87 patients with adequate
      clinical descriptions, the skin lesions either improved significantly (or
      resolved) when the underlying neoplasm was treated or they remained unchanged in
      the setting of persistent disease. Occasionally, the reappearance of skin lesions
      has signaled a recurrence of the tumor.

PMID- 7640202
TI  - Carney complex: the complex of myxomas, spotty pigmentation, endocrine
      overactivity, and schwannomas.
AB  - The complex of myxomas, spotty pigmentation, endocrine overactivity, and
      schwannomas (the Carney complex) is a multisystem tumorous disorder that is
      transmitted as a mendelian autosomal dominant trait. Approximately 150 affected
      patients are known worldwide. The myxomas, which tend to be multiple in the
      involved organ, affect the heart, skin and breast. Typical sites for the skin
      myxomas are the eyelids, external ear canal, and nipples. The lesions commonly
      recur after excision. The spotty skin pigmentation includes lentigines and blue
      nevi, but ephelides and junctional and compound nevi also occur. The lentigines
      are widespread and typically involve the centrofacial area, including the
      vermilion border of the lips, and the conjunctiva, especially the lacrimal
      caruncle and the conjunctival semilunar fold. One or more intraoral pigmented
      spots are seen occasionally. The blue nevi occur on the face, trunk, and limbs,
      but not the hands and feet. Endocrine overactivity includes Cushing's syndrome
      (caused by primary pigmented nodular adrenocortical disease), acromegaly (caused
      by growth hormone-producing pituitary adenoma), and sexual precocity (caused by
      large-cell calcifying Sertoli cell tumor). The schwannomas are a special
      histological type, featuring psammoma bodies and melanin. Most commonly, they
      affect the upper gastrointestinal tract and sympathetic nerve chains, but a few
      have occurred in the skin. The most serious component of the Carney complex is
      cardiac myxoma. Patients suspected of having the syndrome (and their primary
      relatives) should be examined for this neoplasm.

PMID- 7640203
TI  - Degos syndrome: malignant atrophic papulosis.
AB  - Malignant atrophic papulosis is a rare disorder characterized by pathognomonic
      cutaneous lesions that have been associated with multiple infarctive thrombotic
      lesions of other viscera, most notably the gastrointestinal tract and the central
      nervous system. Systemic involvement may develop from weeks to years after the
      onset of the characteristic cutaneous lesions or, rarely, may precede the
      cutaneous lesions. However, the existence of patients with a prolonged, purely
      cutaneous variant of this disease has been increasingly appreciated, and this
      brings into question the appropriateness of applying the term "malignant" to all
      patients who have the peculiar characteristic cutaneous lesions of malignant
      atrophic papulosis. Despite half a century of sporadic investigation, the precise
      cause of this disease remains unknown, and accurate classification of this entity
      as a primary vasculopathy or primary coagulopathy has not been possible.
      Unfortunately, no effective therapy exists for those patients in whom systemic
      involvement develops.

PMID- 7640204
TI  - Cholera in 1994. Part II.

PMID- 7640205
TI  - The molecular detection of circulating tumour cells.

PMID- 7640206
TI  - Growth arrest vs direct cytotoxicity and the importance of molecular structure
      for the in vitro anti-tumour activity of ether lipids.
AB  - A panel of 25 different lipid agents was evaluated for in vitro activity against
      HT29 human colon carcinoma and HL60 promyelocytic leukaemia cells by 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The structure
      activity relationships seen with this series, including those for four sets of
      positional or stereoisomers, indicate that specific receptor proteins are
      unlikely as targets for anti-tumour lipid (ATL) action. Additional data confirm
      the lack of involvement of the platelet-activating factor receptor in particular
      and suggest that metabolic stability is a most important determinant of ATL
      activity. More detailed studies, with 1-O-octadecyl-2-O-methyl-rac-glycero-3
      phosphocholine (ET18-OCH3) and (+/-)-2-(Hydroxy[tetrahydro-2
      (octadecyloxy)methylfuran-2- yl]methoxyphosphinyloxy)-N,N,N,
      trimethylethaniminium hydroxide (SRI 62-834), suggest three different modes of
      activity, depending on drug concentration and exposure time. Low doses of up to 5
      microM in standard serum-containing medium cause population growth arrest after
      prolonged exposure. Growth arrest was associated with a leaky G2/M block as
      determined by flow cytometry. These effects are reversible. Intermediate
      concentrations (5-40 microM) were cytotoxic, causing a net reduction in cell
      numbers after 2-3 days. At even higher concentrations, all lipids caused rapid,
      direct membrane lysis. When the clonogenic assay was used to assess the effects
      of ATLs, most agents reduced colony formation at concentrations above 5 microM.
      However, some compounds proved stimulatory at nanomolar concentrations,
      suggesting that they might possess mitogenic properties. These results,
      particularly those concerning the concentration and time dependence, may be
      relevant to current clinical trials with ether lipids.

PMID- 7640207
TI  - Reversal of radiation-induced cisplatin resistance in murine fibrosarcoma cells
      by selective modulation of the cyclic GMP-dependent transduction pathway.
AB  - Cisplatin resistance, induced in murine fibrosarcoma cells (SSK) in vitro or in
      vivo by low-dose irradiation, can be overcome by activation of the cyclic
      GMP(cGMP)-dependent transduction pathway. This is mediated either by stimulating
      cGMP formation with sodium nitroprusside or by replacing cGMP with a selective
      activator of the cGMP-dependent protein kinase, 8-bromo-cGMP. The cyclic AMP
      dependent transduction pathway is not involved in cisplatin resistance. Instead,
      activation of cAMP sensitises both parental and resistant SSK cells equally to
      the action of cisplatin. There is a 1.8 to 2.5-fold increase in drug toxicity,
      depending on the activating agent. Enhancement of cisplatin sensitivity is
      induced by specific inhibition of cAMP hydrolysis, increase in cAMP formation or
      by increasing the activation potential to cAMP-dependent protein kinase by
      specific cAMP analogues. Cells that have lost cisplatin resistance respond to
      cGMP- or cAMP-elevating agents in the same way as the parental SSK cells. The
      radiation sensitivity is unchanged in all cell lines, even after activation of
      cAMP or cGMP. These results suggest that specific DNA repair pathways are altered
      by radiation but affected only in cisplatin damage repair, which is regulated by
      cGMP. Although there is ample cooperativity and interaction between the cAMP- and
      the cGMP-dependent transduction pathways, specific substrate binding by cGMP
      appears to play an important role in radiation-induced cisplatin resistance.

PMID- 7640208
TI  - Human papillomavirus DNA and TP53 mutations in lung cancers from butchers.
AB  - To investigate whether the high frequency of human papillomavirus infection in
      butchers may be linked to their higher than average incidence of lung cancer, we
      have examined lung cancers from 40 butchers and 26 controls for the presence of
      DNA from both HPV type 7, which is found almost uniquely in hand warts from
      butchers and fishermen, and for those HPV types associated with laryngeal and
      genital cancers. No HPV 7, and only a low frequency of HPV DNA was found,
      suggesting that HPV infection does not make an important contribution to the
      elevated levels of lung cancer in meat handlers. In addition, the frequency of
      p53 mutation was shown to be slightly lower than previously reported in lung
      cancers.

PMID- 7640209
TI  - Altered MRP is associated with multidrug resistance and reduced drug accumulation
      in human SW-1573 cells.
AB  - We have analysed the contribution of several parameters, e.g. drug accumulation,
      MDR1 P-glycoprotein (P-gp), multidrug resistance-associated protein (MRP) and
      topoisomerase (topo) II, to drug resistance in a large set of drug-resistant
      variants of the human non-small-cell lung cancer cell line SW-1573 derived by
      selection with low concentrations of doxorubicin or vincristine. Selection with
      either drug nearly always resulted in MDR clones. The resistance of these clones
      could be explained by reduced drug accumulation and was associated with a
      decrease rather than an increase in the low MDR1 mRNA level. To test whether a
      decrease in MDR1 mRNA indirectly affected resistance in these cells, we
      introduced a MDR1-specific hammerhead ribozyme into wild-type SW-1573 cells.
      Although this led to a substantial reduction in MDR1 mRNA, it did not result in
      resistance. In all resistant clones we found an altered form of the multidrug
      resistance-associated protein (MRP), migrating slightly slower during SDS
      polyacrylamide gel electrophoresis than MRP in parental cells. This altered MRP
      was also present in non-P-gp MDR somatic cell hybrids of the SW-1573 cells,
      demonstrating a clear linkage with the MDR phenotype. Treatment of crude cellular
      membrane fractions with N-glycanase, endoglycosidase H or neuraminidase showed
      that the altered migration of MRP on SDS-PAGE is due to a post-translational
      modification. There was no detectable difference in sialic acid content. In most
      but not all doxorubicin-selected clones, this MDR phenotype was accompanied by a
      reduction in topo II alpha mRNA level. No reduction was found in the clones
      selected with vincristine. We conclude from these results that selection of the
      SW-1573 cell line for low levels of doxorubicin or vincristine resistance,
      predominantly results in MDR with reduced drug accumulation associated with the
      presence of an altered MRP protein. This mechanism can be accompanied by other
      resistance mechanisms, such as reduced topo II alpha mRNA in case of doxorubicin
      selection.

PMID- 7640210
TI  - P-glycoprotein is not expressed in a majority of colorectal carcinomas and is not
      regulated by mutant p53 in vivo.
AB  - Overexpression of the MDR1 product, P-glycoprotein (Pgp), has been shown to be
      one of the mechanisms underlying the development of multidrug resistance (MDR).
      Recently, one mutant p53 has been shown to stimulate the MDR1 gene promoter in
      vitro, whereas wild-type p53 repressed this activity. We measured Pgp and p53
      expression by immunoblotting in 34 colorectal tumours, and performed mutation
      analyses on the p53-positive tumours to confirm the presence of mutant p53
      protein. Tumour DNA indices (DIs) were also measured using flow cytometry. Pgp
      was detected in 44% (15/34) of the tumours and in 100% (13/13) of the normal
      mucosas (P = 0.0005), with highest levels of expression seen in normal mucosa,
      suggesting that initial drug resistance in colorectal tumours is not caused by
      Pgp. Highly DNA aneuploid tumours demonstrated the lowest levels of Pgp
      expression relative to moderately aneuploid and diploid colorectal tumours. p53
      protein was detected in 53% (18/34) of the tumours, and 12 of 14 p53-positive
      tumours had p53 gene mutations, p53-negative tumours had approximately twice the
      level of Pgp expression of p53-positive tumours. Pgp expression was not
      associated with either p53 expression (P = 0.73) or incidence of p53 gene
      mutation (P = 0.70), suggesting that mutant p53 does not induce Pgp
      overexpression in colorectal carcinomas.

PMID- 7640212
TI  - Phenotype of glutathione S-transferase Mu (GSTM1) and susceptibility to malignant
      melanoma. MMM group. Multidisciplinary Malignant Melanoma Group.
AB  - The isoenzyme Mu of glutathione S-transferase (GSTM1) is dominantly inherited,
      and the prevalence of this isoenzyme in the population is about 60%. The lack of
      GSTM1 has been linked with cancer risk. The frequency of the phenotypes of this
      isoenzyme in melanoma (MM) patients (n = 197) is reported here. A significantly
      higher proportion of individuals in the control group (n = 147) had measurable
      GSTM1 than MM patients (59.1% vs 42%, P = 0.002); there was a higher proportion
      of positive phenotypes in general among women than among men. Odds ratio analysis
      indicated that individuals with this polymorphic variant have an approximately 2
      fold risk of developing these cancers. GSTM1 phenotype distribution depends on
      age, smoking habit and tumour pathology. A group of MM patients with dysplastic
      naevi was also studied.

PMID- 7640213
TI  - Differential patterns of placental and epithelial cadherin expression in basal
      cell carcinoma and in the epidermis overlying tumours.
AB  - P-cadherin (P-CD) and E-cadherin (E-CD) are expressed by keratinocytes and play
      an important role in skin morphogenesis. P-CD expression is restricted to the
      basal layer of normal epidermis, whereas E-CD is expressed in all the living
      layers. We have previously reported a reduced expression of E-CD in most cases of
      infiltrative basal cell carcinoma (BCC). In the present work we have investigated
      by immunohistochemistry the expression of both P-CD and E-CD in a new series of
      32 patients with BCC. Most cases of superficial multicentric BCC and some nodular
      tumours had preserved expression of both cadherins in all tumour cells. The
      majority of nodular BCCs had partially reduced expression of one or both
      cadherins with an ordered distribution of cells showing different cadherin
      staining throughout the tumour mass. A severe reduction of E-CD expression with a
      disordered distribution of cells with different immunostaining intensity was
      observed in most specimens of infiltrative BCC. In contrast, P-CD expression was
      preserved in all cases of infiltrative BCC. These results suggest that P-CD and E
      CD play different roles in the growth pattern of BCC. In addition, both anomalous
      P-CD expression and reduced E-CD expression were frequently observed in the
      spinous layer of epidermis overlying tumours. This phenomenon was significantly
      associated with the presence of keratinocytic atypia, which suggests that
      disturbed cadherin expression could be a marker of premalignant changes and/or
      hyperproliferative activity in human epidermis.

PMID- 7640211
TI  - The novel fluorinated 2-nitroimidazole hypoxia probe SR-4554: reductive
      metabolism and semiquantitative localisation in human ovarian cancer
      multicellular spheroids as measured by electron energy loss spectroscopic
      analysis.
AB  - The novel fluorinated 2-nitroimidazole SR-4554 is undergoing preclinical
      development as a magnetic resonance spectroscopy and imaging probe for hypoxic
      tumour cells. We have used electron energy loss spectroscopic analysis (EELS) to
      show selective reduction and differential subcellular localisation of SR-4554 in
      human ovarian multicellular spheroids. SR-4554 was demonstrated to be metabolised
      by these A2780 cells under hypoxic but not under normal aerobic cell culture
      conditions. The EELS technique illustrated that the relative amount of drug
      within the cytoplasm of cells from both the inner region (150-160 microns from
      edge) and outer edge of the spheroid did not differ significantly after an
      initial 3 h incubation with drug. In contrast, an 8-fold differential between the
      amount of drug retained in the cytoplasm (primarily ribosomes and endoplasmic
      reticulum) of cells from the inner vs outer regions of the spheroids was observed
      following a subsequent 2 h 'chase' culture in drug-free medium. Within cells from
      the hypoxic region of the spheroid, SR-4554 was mainly associated with the
      endoplasmic reticulum, nucleus and the cytoplasmic side of intracellular vesicles
      and also to a lesser extent with the nuclear periphery. Interestingly, the drug
      was only weakly associated with the mitochondria and plasma membrane of the
      cells. The characteristics of cellular and subcellular distribution of SR-4554
      are consistent with the hypothesis that 2-nitroimidazole compounds undergo
      hypoxia-mediated enzymatic reduction to reactive species. These reactive species
      are selectively retained in the cells in which they are metabolised through
      covalent association with subcellular components. These findings provide
      additional support for the clinical development of the drug as a non-invasive
      probe for tumour hypoxia and at the same time illustrate the utility of the EELS
      technique for examining the heterogeneity of drug distribution both between and
      within cells.

PMID- 7640215
TI  - Effect of thalidomide on tumour necrosis factor production and anti-tumour
      activity induced by 5,6-dimethylxanthenone-4-acetic acid.
AB  - The investigational anti-tumour agent, 5,6-dimethylxanthenone-4-acetic acid (5,6
      MeXAA), an analogue of flavone acetic acid (FAA), has been scheduled for clinical
      evaluation. Like FAA, 5,6-MeXAA exhibits excellent experimental anti-tumour
      activity and is an efficient inducer of cytokines in mice. We have examined the
      effect of pharmacological suppression of tumour necrosis factor (TNF) production
      on the anti-tumour activity of 5,6-MeXAA, taking advantage of previous
      observations that TNF production in response to endotoxin in vitro is inhibited
      by thalidomide. Thalidomide at doses of between 8 and 250 mg kg-1 efficiently
      suppressed serum TNF activity in response to 5,6-MeXAA at its optimal TNF
      inducing dose of 55 mg kg-1. Suppression was achieved when thalidomide was
      administered at the same time as, or up to 4 h before, 5,6-MeXAA. Under
      conditions in which TNF activity was suppressed, the degree of tumour
      haemorrhagic necrosis and the proportion of cures in the subcutaneous Colon 38
      tumour were increased. In mice administered thalidomide (100 mg kg-1) together
      with 5,6-MeXAA (30 mg kg-1), complete tumour regression was obtained in 100% of
      mice, as compared with 67% in mice receiving 5,6-MeXAA alone. The results suggest
      a possible new application for thalidomide and pose new questions about the
      action of 5,6-MeXAA and related compounds.

PMID- 7640214
TI  - Hyperthermia, thermotolerance and topoisomerase II inhibitors.
AB  - The cytoxicity of both intercalating (m-AMSA) and non-intercalating (VP16, VM26)
      topoisomerase II-targeting drugs is thought to occur via trapping DNA
      topoisomerase II on DNA in the form of cleavable complexes. First, analysis of
      cleavable complexes (detected as DNA double-strand breaks) by pulsed-field gel
      electrophoresis confirmed the correlation between cleavable complex formation and
      cytotoxicity of three topoisomerase-targeting drugs in HeLa S3 cells (the order
      of effects being VM26 > m-AMSA > VP16). In contrast to many antineoplastic
      agents, hyperthermic treatments were found to protect cells against the toxicity
      of all three topoisomerase II drugs. Hyperthermia treatment does not alter drug
      accumulation but reduces the ability of the drug-topoisomerase II complex to form
      the cleavable complexes. Nuclear protein aggregation induced by heat at the sites
      of topoisomerase II-DNA interaction may explain such an effect. In thermotolerant
      cells, the toxic effects of VP16 but not m-AMSA were reduced. For both drugs,
      however, the status of thermotolerance did not affect cleavable complex formation
      by the drugs. Thus, protection against VP-16 toxicity seems not to be associated
      with heat-induced activation of the P-gp 170 pump or altered topoisomerase II-DNA
      interactions. Rather, a protective (heat shock protein mediated?) mechanism
      against non-intercalating topoisomerase II drugs seems to occur at a stage after
      DNA-drug interaction. Finally, heat treatment before topoisomerase II drug
      treatment reduced toxicity and cleavable complex formation in thermotolerant
      cells to about the same extent as in non-tolerant cells, consistent with the
      presumption of nuclear protein aggregation being responsible for this effect.

PMID- 7640216
TI  - Mechanisms for optimising photodynamic therapy: second-generation
      photosensitisers in combination with mitomycin C.
AB  - Mechanisms for improving photodynamic therapy (PDT) were investigated in the
      murine RIF1 tumour using meso-tetrahydroxyphenylchlorin (m-THPC) or
      bacteriochlorin a (BCA) as photosensitisers and comparing these results with
      Photofrin-mediated PDT. The 86Rb extraction technique was used to measure changes
      in perfusion at various times after interstitial PDT. Non-curative combinations
      of light doses with m-THPC and BCA PDT markedly decreased vascular perfusion.
      This decrease was more pronounced for both new photosensitisers than for
      Photofrin. Comparison of tumour perfusion after PDT with tumour response revealed
      an inverse correlation for all three photosensitisers, but the relationship was
      less clear for m-THPC and BCA. In vivo/in vitro experiments were performed after
      Photofrin or m-THPC PDT in order to assess direct tumour kill (immediate plating)
      vs indirect vascular effects (delayed plating). For both photosensitisers, there
      was little direct cell killing but clonogenic survival decreased as the interval
      between treatment and excision increased. When m-THPC PDT was combined with
      mitomycin C (MMC), light doses could be decreased by a factor of 2 for equal
      tumour effects. Lower light and m-THPC doses could be used compared with
      Photofrin PDT in combination with MMC. BCA PDT with MMC did not result in a
      greater tumour response compared with BCA PDT alone. Reduction in both light and
      photosensitiser does for effective PDT regimes in combination with MMC offers
      substantial clinical advantages, since both treatment time and skin
      photosensitisation will be reduced.

PMID- 7640217
TI  - Analysis of p16 gene deletion and point mutation in breast carcinoma.
AB  - We looked for p16 gene deletion by Southern analysis and p16 gene point mutation
      by single-stranded conformation polymorphism (SSCP) analysis and direct
      sequencing of DNA from fresh tumour samples of 35 and 33 breast carcinomas
      respectively. No homozygous p16 gene deletion was found in any case. A missense
      point mutation of the p16 gene was found in only one patient. This point mutation
      was absent from the patient's lymphocytes, ruling out a polymorphism or a
      germline mutation. These findings suggest that p16 gene alterations are rarely
      observed in breast carcinoma.

PMID- 7640219
TI  - Epidermal growth factor, oestrogen and progesterone receptor expression in
      primary ovarian cancer: correlation with clinical outcome and response to
      chemotherapy.
AB  - The expression of epidermal growth factor receptor (EGFR), oestrogen receptor
      (ER) and progesterone receptor (PR) was assayed by a radioreceptor method in 117
      primary ovarian cancers. EGFR was not significantly related to any of the
      clinicopathological parameters examined. In patients with stage II-IV disease who
      underwent second-look surgery after primary chemotherapy, a significant
      correlation between high EGFR levels and poor response to chemotherapy was
      demonstrated (P = 0.031). Moreover, post-operative residual tumour showed an
      independent role in predicting chemotherapy response (P = 0.0007) and EGFR status
      showed a borderline significance (P = 0.052) in the multivariate analysis. No
      correlation between steroid hormone receptors and clinicopathological parameters
      was observed. Whereas a significant relationship was shown between EGFR
      positivity and a shorter overall survival (OS) (P = 0.0022) and progression-free
      survival (PFS) (P = 0.0033), patient survival was not related to steroid hormone
      receptor status. Among the parameters tested only stage, ascites and EGFR status
      retained an independent prognostic value in the multivariate analysis.

PMID- 7640218
TI  - Prognostic value of bcl-2 expression in invasive breast cancer.
AB  - Expression of the bcl-2 proto-oncogene was studied immunohistochemically in 251
      invasive ductal breast carcinomas (median follow-up time 91 months, range 24-186
      months) and the results were correlated with clinicopathological data and
      prognostic variables. Sixty-three (25%) tumours were scored bcl-2 negative and
      188 (75%) tumours were bcl-2 positive. No relationship could be observed between
      bcl-2 status and tumour grade, pTNM staging or menopausal status. A strong
      positive relationship was demonstrated between bcl-2 immunoreactivity and
      oestrogen receptor status (P < 0.001) and progesterone receptor status (P <
      0.001). No prognostic value was demonstrated for bcl-2 expression on disease-free
      survival and overall survival in axillary node-negative breast cancer patients.
      However, in axillary node-positive breast cancer patients multivariate analysis
      demonstrated absence of bcl-2 expression to be independently related to shortened
      disease-free survival (P = 0.003) and shortened overall survival (P < 0.001). Our
      results suggest a potential important role for bcl-2 expression as a modulator of
      response to adjuvant therapy in breast cancer.

PMID- 7640221
TI  - Microsatellite instability in ovarian neoplasms.
AB  - Microsatellite instability has been observed in a variety of sporadic
      malignancies, but its existence in sporadic ovarian cancer has been the subject
      of conflicting reports. We have performed a polymerase chain reaction-based
      microsatellite analysis of DNAs extracted from the neoplastic and non-neoplastic
      tissues of 41 ovarian cancer patients. Tumour-associated alterations were
      observed in seven (17%) of these cases. Clinicopathological correlations revealed
      that: (1) alterations among tumours classified as serous adenocarcinomas occurred
      with relatively low frequency (2/24 or 8%); (2) most of the tumours with
      microsatellite alterations (5/7 or 71%) were of less common histopathological
      types (epithelial subtypes such as endometrioid and mixed serous and mucinous, or
      non-epithelial types such as malignant mixed Mullerian or germ cell tumours); (3)
      tumour-associated alterations were observed in 3/4 (75%) of the patients with
      stage I tumours vs 4/37 (11%) of the patients with stage II, III and IV tumours
      (P = 0.01); (4) tumour-associated microsatellite instability was found to occur
      with similar frequencies among patients with and without clinical features
      suggestive of familial disease, including positive family history, early onset,
      or multiple primary tumours. In summary, we have observed microsatellite
      alterations in the neoplastic tissues of ovarian cancer patients with diverse
      genetic backgrounds and clinicopathological features. The pattern of alterations
      is consistent with the possibility that multiple mechanisms may be responsible
      for microsatellite instability in ovarian neoplasms.

PMID- 7640220
TI  - Chromosome 11 allele imbalance and clinicopathological correlates in ovarian
      tumours.
AB  - Allele imbalance on chromosome 11 loci in ovarian cancer is a frequent event,
      suggesting the presence of tumour-suppressor genes for ovarian carcinogenesis on
      this chromosome. Ten highly polymorphic (CA) repeat microsatellites were used to
      determine allele imbalance in 60 primary ovarian tumours, including 47 epithelial
      ovarian cancers (EOCs). Forty EOCs (85%) showed allele imbalance at one or more
      loci, and in 39 of these (83%) the data suggested subchromosomal deletions: eight
      of 11p only; six of 11q only; and 25 of both 11p and 11q. Three consensus regions
      of deletion were indicated at 11p15.5-p15.3, 11q12-q22 and 11q23.3-q24.1. Allele
      imbalance at the 11q subtelomeric region (D11S912) correlated significantly with
      adverse survival, while imbalance at 11q14.3 and retention of heterozygosity at
      11q22 (close to the site of the progesterone receptor gene) were associated with
      favourable clinicopathological features. The findings allow development of a
      preliminary model for the molecular evolution of epithelial ovarian cancer.

PMID- 7640222
TI  - Evidence for the presence of two tumour-suppressor genes for hepatocellular
      carcinoma on chromosome 13q.
AB  - The concept that genetic changes accumulate during development and progression of
      cancer is widely accepted. Frequent allelic losses at chromosome 13q have been
      found in hepatocellular carcinomas (HCCs), and a known tumour-suppressor at
      13q14, the retinoblastoma (RB) gene, is thought to be the target of those events.
      However, no strong evidence has emerged to support a significant role of RB
      during hepatocarcinogenesis. To investigate the minimal area(s) of loss on
      chromosome 13q in HCCs, we analysed DNAs isolated from 92 tumours for loss of
      heterozygosity (LOH) at 13 loci on chromosome 13q, using polymorphic
      microsatellite markers. In 30 (32.6%) of 92 cases we detected LOH for at least
      one locus on chromosome 13q and 20 revealed a partial or interstitial deletion of
      chromosome 13q. Deletion mapping of these 20 tumours indicated two separate
      commonly deleted regions: one was located in the region including RB and the
      other was located in the region including the BRCA2 locus. These findings suggest
      that at least one putative tumour-suppressor gene for HCC other than RB, possibly
      BRCA2, exists on chromosome 13q.

PMID- 7640223
TI  - The induction of apoptosis in human mammary luminal epithelial cells by
      expression of activated c-neu and its abrogation by glucocorticoids.
AB  - The effects of expressing neu-T, a mutated constitutively activated form of c
      neu, have been examined in the non-transformed conditionally immortalised human
      mammary luminal epithelial cell line, HB4a. A variant cell line, N4.1, which
      expressed neu-T, showed evidence of transformation, including partial loss of
      growth factor dependence and acquisition of anchorage-independent growth, but
      failed to give rise to tumours in nude mice, indicating that expression of neu-T
      alone was probably insufficient to cause tumorigenic progression to a full
      malignant phenotype. During characterisation of the N4.1 cell line, it was
      observed that under conditions of serum deprivation, it underwent apoptotic cell
      death, as demonstrated by light microscopy, flow cytometry and DNA gel
      electrophoresis. The induction of apoptotic cell death in the N4.1 cell line by
      serum deprivation was abrogated specifically by the addition of steroids with
      glucocorticoid activity but not any peptide growth factors studied. This study
      shows the induction of apoptosis by serum deprivation, and its abrogation by
      glucocorticoids occurring in human mammary luminal epithelial cells transformed
      by expression of neu-T, and implicates the involvement of receptor protein
      tyrosine kinases in an apoptotic signalling pathway in this cell type.

PMID- 7640224
TI  - Homozygous deletion frequency and expression levels of the CDKN2 gene in human
      sarcomas--relationship to amplification and mRNA levels of CDK4 and CCND1.
AB  - Homozygous deletions of the putative tumour-suppressor gene CDKN2, which encodes
      an inhibitor of cdk4, have been detected in a high percentage of cancer cell
      lines of various histological types. In the present study, 109 human sarcomas
      were examined for homozygous deletions and for mRNA expression levels of the
      CDKN2 gene. Altogether, deletions were found in only eight (7%) of the cases,
      but, interestingly, in two (of eight) malignant Schwannomas and in two (of five)
      rhabdomyosarcomas. In comparison, such deletions were seen in only one (of 21)
      osteosarcomas and in none of 20 MFHs and 21 liposarcomas. Notably, highly
      elevated CDKN2 mRNA levels were found in 33% of the sarcomas, whereas no
      detectable transcript was present in 12 normal tissues. Amplifications of CDK4
      and CCND1 (cyclin D1) were observed in 11% and 4% of the sarcomas respectively,
      but never in tumours with CDKN2 deletions. The level of CDK4 mRNA expression was
      increased in nine tumours in addition to the 12 samples with CDK4 amplification.
      Increased levels of the cyclin D1 transcript was found in 37 cases, four with and
      33 without amplification. The data indicate that aberrations of these
      functionally related genes, or in regulation of the expression of the kinase, the
      activator or the inhibitor, may participate in sarcoma development. Furthermore,
      the data suggest that homozygous CDKN2 deletions may be of dissimilar
      significance in different sarcoma subtypes.

PMID- 7640225
TI  - Characterisation of a human small-cell lung cancer cell line resistant to the DNA
      topoisomerase I-directed drug topotecan.
AB  - Camptothecins are DNA topoisomerase I-directed anti-tumour drugs with a novel
      mechanism of action. Topotecan (TPT), a hydrophilic derivative of camptothecin,
      is currently undergoing phase II clinical trials in small-cell lung cancer
      (SCLC). Human SCLC OC-NYH cells were made more than 6-fold resistant to topotecan
      by stepwise drug exposure and resistance was stable for 70 passages without drug.
      NYH/TPT cells had half the topoisomerase I level and activity of wild-type cells.
      However, no difference in camptothecin or topotecan inhibition of topoisomerase I
      mediated DNA relaxation was found, indicating that the enzyme itself was
      unchanged in the resistant cell. In NYH/TPT cells, topoisomerase II alpha and
      beta levels were increased approximately 2-fold. Accordingly, the topoisomerase
      II-directed drug etoposide (VP-16) induced an increased number of DNA single
      strand breaks in NYH/TPT cells. However, sensitivity to different topoisomerase
      II-targeting agents in NYH/TPT cells varied from increased to decreased,
      indicating a role for as yet unidentified factors acting on the pathway to cell
      death after topoisomerase II-induced DNA damage has occurred. Of 20 anti-cancer
      agents tested, only hydroxyurea showed marked collateral hypersensitivity in
      NYH/TPT cells.

PMID- 7640226
TI  - Frequency of down-regulation of individual HLA-A and -B alleles in cervical
      carcinomas in relation to TAP-1 expression.
AB  - The development of cervical carcinoma is strongly associated with specific types
      of human papillomaviruses (HPVs). A role for cellular immunity in cervical
      disease is supported by the increased occurrence of HPV-associated lesions in
      immunosuppressed individuals. Upon viral infection or malignant transformation,
      ensuing alterations in gene expression result in the generation of novel sets of
      peptides which can form complexes with specific HLA class I heavy chains and beta
      2-microglobulin. These are then expressed at the cell surface as potential
      targets for specific T cells. In this study of 100 carcinomas HLA-A and -B class
      I expression by the tumour cells was down-regulated at one or more alleles in at
      least 73% of cervical carcinomas. Interference with the transporter associated
      with antigen presentation (TAP), which translocates cytosolic peptides from
      endogenously synthesised proteins (e.g. viral) into the lumen of the endoplasmic
      reticulum was found in 38% of the HLA class I down-regulated tumours. Loss of
      expression for common HLA class I alleles ranged from 36% to 71%, and such
      changes might be expected to influence specific immunogenic peptide presentation
      and consequent immune recognition. These results underline the importance of
      single as well as multiple allelic loss in cervical neoplasia and have important
      implications for attempts to intervene immunologically in cervical cancer.

PMID- 7640228
TI  - Improvements in diagnosis have changed the incidence of histological types in
      advanced gastric cancer.
AB  - The data on 912 patients with early cancer and 1245 with advanced cancer who were
      seen between 1971 and 1990 were compared. The incidence of undifferentiated-type
      cancer increased significantly in patients with advanced gastric cancer, but not
      in patients with early gastric cancer. When the histological types were compared
      with regard to sex, age and location in patients with early gastric cancer the
      undifferentiated type was found to increase only in males, while in patients with
      advanced gastric cancer the undifferentiated type increased in both sexes as well
      as in younger patients and in both the upper and middle third of the stomach.
      These differences in the trends between early and advanced cancers are probably
      due to the different degrees of diagnostic accuracy for the early detection of
      histological types.

PMID- 7640227
TI  - Chemosensitisation of spontaneous multidrug resistance by a 1,4-dihydropyridine
      analogue and verapamil in human glioma cell lines overexpressing MRP or MDR1.
AB  - Multidrug resistance phenotypes in human tumours are associated with the
      overexpression of the 170 kDa P-glycoprotein encoded by the multidrug resistance
      1 (MDR1) gene, and also with that of the non-P-glycoprotein-mediated multidrug
      resistance gene, MRP, which encodes a 190 kDa membrane ATP-binding protein. We
      have previously reported that overexpression of MRP appears to be responsible for
      spontaneous multidrug resistance in some human glioma cell lines (Abe et al.,
      Int. J. Cancer, 58, 860-864, 1994). In this study, we investigated whether
      chemosensitising agents of P-glycoprotein-mediated multidrug resistance such as
      verapamil, a biscoclaurine alkaloid (cepharanthine), and a dihydropyridine
      analogue (NIK250) could also reverse multidrug resistance in human glioma cells.
      The glioma cell lines were the two MRP-expressing cell lines, T98G and IN500, an
      MDR1-expressing cell line, CCF-STTG1, and the MRP1 MDR1-non-expressing cell line,
      IN157. Verapamil and NIK250 almost completely reversed drug resistance to
      vincristine, etoposide and doxorubicin in T98G cells, while they also reversed
      drug resistance to vincristine and etoposide, but only partially to doxorubicin
      in IN500 cells. Cepharanthine as well as verapamil and NIK250 reversed
      vincristine resistance in CCF-STTG1 cells, but cepharanthine only partially
      reversed drug resistance in T98G and IN500 cells. The cellular accumulation of
      [3H]etoposide increased about 2- and 3-fold compared with control in T98G cells
      in the presence of verapamil and NIK250 respectively. Furthermore, the release of
      doxorubicin from the nuclei of T98G cells was blocked by NIK250. However, NIK250
      and verapamil caused no apparent increase in vincristine accumulation in T98G
      cells. NIK250 or verapamil might exert inhibitory effects upon MRP function,
      resulting in a reversal of MRP-mediated spontaneous multidrug resistance in
      cultured human glioma cells.

PMID- 7640229
TI  - Cellular kinetics in rectal cancer.
AB  - Measurements of dynamic tumour cell kinetic parameters, particularly the
      potential doubling time (Tpot) may have potential as predictive assays for
      treatment outcome after radiotherapy. This paper details the distributions of
      Tpot and other kinetic and DNA content parameters measured in rectal cancers.
      Biopsies were taken from 119 patients approximately 6 h after infusion of 200 mg
      m-2 bromodeoxyuridine (BrdUrd). The samples were analysed by bivariate DNA/BrdUrd
      flow cytometry. The primary purpose of the study was to measure the kinetic
      parameters of labelling index (LI), duration of S-phase (TS) and Tpot.
      Secondarily, tumour DNA ploidy (DNA index) and S-phase fractions (SPFs) were also
      estimated from the univariate DNA histograms. The 101 evaluable patients were
      classified according to clinical stage as T2 (n = 12), T3 (n = 53), T4 (n = 28)
      or recurrent tumours (n = 8). Of the evaluable tumours, 73 were DNA aneuploid.
      The median LI, TS, and Tpot of the aneuploid tumours were 21%, 20 h and 3.3 days
      respectively. The calculated LI, TS, and Tpot of diploid tumours were subject to
      uncertainties because of the contribution of normal cells. The LI and SPF of all
      tumours were, however, significantly (P < 0.001) correlated, having a correlation
      coefficient of only 0.76. The wide distributions of values for LI (quartiles
      13.5%, 26.9%) and Tpot (quartiles 2.4, 5.6 days) that were found are necessary
      baseline information if these parameters are to be useful in individual treatment
      selection or as predictors of treatment outcome.

PMID- 7640231
TI  - Increased soluble interleukin-2 receptor concentration in plasma predicts a
      decreased cellular response to IL-2.
AB  - Interleukin 2 (IL-2) immunotherapy has met with limited success in the treatment
      of renal cell carcinoma (RCC) and malignant melanoma (MM). However, non
      responders still account for up to 80% of those patients receiving IL-2. A high
      concentration of soluble IL-2 receptor (sIL-2R) is commonly found in the blood of
      such patients. We investigated the possibility that high sIL-2R concentration
      pretreatment may interfere with the bioavailability of IL-2. The mean
      concentration of sIL-2R in plasma from patients with MM, RCC and head and neck
      cancer was 3378 U ml-1, 8778 U ml-1 and 764 U ml-1 respectively, compared with
      1315 U ml-1 in plasma from healthy volunteers. Inclusion of plasma from patients
      with RCC and MM patient plasma in cytotoxic T-lymphocyte leukaemic (CTLL) cell/IL
      2 assays inhibited the ability of CTLL cells to respond to IL-2, and an inverse
      correlation was found between the concentration of sIL-2R and the growth response
      of CTLL cell to IL-2 (r = -0.86, P = 0.003). Plasma with soluble IL-2R
      concentrations greater than 3000 U ml-1 produced a reduction in cell growth of
      more than 50% when included in CTLL IL-2 assays. The addition of increasing
      concentrations of IL-2 to cultures containing suppressive plasma failed to
      restore CTLL cell growth response to normal. Failure to saturate sIL-2R by
      exogenous IL-2 addition therefore suggests that another factor, initially present
      at a concentration similar to the sIL-2R concentration, is responsible for the
      observed effect. Determination of the suppressive effect of patient plasma as
      presented here may allow more effective IL-2 dosing schedules.

PMID- 7640230
TI  - Increased thromboembolic incidence in anti-cardiolipin-positive patients with
      malignancy.
AB  - This study was undertaken to determine the prevalence of anti-cardiolipin
      antibodies (ACLAs) in patients with malignancy and to investigate a possible
      association of ACLAs with thromboembolic events in such patients. The study
      included 216 patients with solid and non-solid malignancies and an age-matched
      control group of 88 healthy subjects. ACLA levels were measured and related to
      thromboembolic phenomena (diagnosed by imaging methods) that occurred within 12
      months of the diagnosis of cancer. Forty-seven patients (approximately 22%) with
      cancer were ACLA positive as compared with only three subjects (approximately 3%)
      in the control group (P < 0.0001). The ACLA-positive cancer patients had a
      significantly higher rate of thromboembolic events than ACLA-negative cancer
      patients: 13 of 47 (28%) vs 24 of 169 (14%), respectively (P < 0.05). High titres
      of either IgG-ACLA or IgM-ACLA were found in 10 out of 13 ACLA-positive cancer
      patients with thrombotic complications, but in only 2 out of 34 cancer ACLA
      positive patients without thromboembolic events (P < 0.0001). In four cancer
      patients in whom ACLA levels were followed ACLA decreased after successful
      surgery/chemotherapy treatment and remained negative and thromboembolic free for
      12 months of follow-up. Patients with malignancies show an increased prevalence
      of ACLA. Furthermore, ACLA-positive patients, mainly those with high titres, are
      much more prone to thromboembolic events.

PMID- 7640232
TI  - Post-operative levamisole may compromise early healing of experimental intestinal
      anastomoses.
AB  - There exists growing interest in immediate post-operative local adjuvant therapy
      after resection of intestinal malignancies. It is therefore necessary to assess
      it potential effect on the healing of intestinal anastomoses. Five groups (n =
      20) of rats underwent resection and anastomosis of both ileum and colon: a
      control group and four experimental groups receiving intraperitoneal 5
      fluorouracil (5-FU), 5-FU plus leucovorin, 5-FU plus levamisole or levamisole
      alone, on the day of surgery and the next 2 days. Animals were killed 3 or 7 days
      after operation. Another three groups (n = 6) of animals were used to compare
      anastomotic collagen synthetic capacity in control rats or rats receiving 5-FU or
      5-FU plus levamisole. On the third post-operative day, the average anastomotic
      bursting pressure in the 5-FU/levamisole group was reduced by 36% as compared
      with the control group, both in ileum (P = 0.02) and in colon (P = 0.01). Values
      in the other groups were similar to those in the control group. Anastomotic
      breaking strength was significantly (P < 0.025) lowered in the ileum from the
      levamisole group at both days 3 and 7. Anastomotic collagen synthetic capacity
      was strongly reduced in the 5-FU and 5-FU/levamisole groups. However, there was
      no significant difference between the control group and the four experimental
      groups with regard to anastomotic hydroxyproline concentration and content,
      either 3 or 7 days after operation. Thus, limited use of levamisole, alone or in
      combination with intraperitoneal 5-FU, may compromise intestinal healing.

PMID- 7640233
TI  - A phase I trial of bryostatin 1 in patients with advanced malignancy using a 24
      hour intravenous infusion.
AB  - Bryostatin 1 is a macrocyclic lactone derived from the marine invertebrate Bugula
      neritina. In vitro, bryostatin 1 activates protein kinase C (PKC), induces the
      differentiation of a number of cancer cell lineages, exhibits anti-tumour
      activity and augments the response of haemopoietic cells to certain growth
      factors. In vivo, bryostatin 1 is also immunomodulatory, but the range of tumours
      which respond to bryostatin 1 in xenograft tumour models is mostly the same as
      the in vitro tumour types, suggesting a direct mode of action. Nineteen patients
      with advanced malignancy were entered into a phase I study in which bryostatin 1
      was given as a 24 h intravenous infusion, weekly, for 8 weeks. Myalgia was the
      dose-limiting toxicity and the maximum tolerated dose was 25 micrograms m-2 per
      week. The myalgia was cumulative and dose related, and chiefly affected the
      thighs, calves and muscles of extraocular movement. The mechanism of the myalgia
      is unknown. CTC grade 1 phlebitis affected every patient for at least one cycle
      and was caused by the diluent, PET, which contains polyethylene glycol, ethanol
      and Tween 80. Most patients experienced a 1 g dl-1 decrease in haemoglobin within
      1 h of commencing the infusion which was associated with a decrease in
      haematocrit. Radiolabelled red cell studies were performed in one patient to
      investigate the anaemia. The survival of radiolabelled red cells during the week
      following treatment was the same as that seen in the week before treatment.
      However, there was a temporary accumulation of radiolabelled red cells in the
      liver during the first hour of treatment, suggesting that pooling of erythrocytes
      in the liver might account for the decrease in haematocrit. Total or activated
      PKC concentrations were measured in the peripheral blood mononuclear cells
      (PBMCs) of three patients for the first 4 h of treatment and during the last hour
      of the infusion. This showed that PKC activity was significantly modulated during
      the infusion. Bryostatin 1 is immunomodulatory in vitro, and we have confirmed
      this activity in vivo. An investigation of the first three cycles of treatment in
      seven patients showed an increased IL-2-induced proliferative response in
      peripheral blood lymphocytes and enhanced lymphokine-activated killer (LAK)
      activity. A previously reported rise in serum levels of interleukin 6 (IL-6) and
      tumour necrosis factor alpha (TNF 1) was not confirmed in our study; of nine
      patients in this study, including patients at all dose levels, none showed an
      increase in these cytokines.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7640234
TI  - Adjuvant chemotherapy for soft-tissue sarcoma: review and meta-analysis of the
      published results of randomised clinical trials.
AB  - Fifteen published randomised trials comparing adjuvant chemotherapy with no
      chemotherapy in soft-tissue sarcoma (STS) were identified (1546 patients). A
      qualitative review and a meta-analysis of this published literature were
      performed. With the qualitative review it was not possible to synthesise the
      apparently conflicting results of individual trials. The meta-analysis of the
      published data suggests an improvement in survival at 2 years (OR = 0.73, 95% CI
      = 0.53-0.99, P = 0.044) and at 5 years (OR = 0.59, 95% CI = 0.45-0.78, P =
      0.0002) in favour of chemotherapy. However, the assumptions and approximations
      required to conduct this quantitative summary demand that the results are
      interpreted with caution. The only reliable means of assessing the current
      evidence on whether adjuvant chemotherapy has a role in the treatment of patients
      with STS, is to collect, check and reanalyse individual patients data (IPD) from
      each trial centrally, and formally combine the results in a stratified time-to
      event analysis. Such an IPD analysis is currently being undertaken by an
      international collaborative group.

PMID- 7640235
TI  - Mammographic densities as a criterion for entry to a clinical trial of breast
      cancer prevention.
AB  - The most convincing evidence that a factor such as dietary fat is causally
      related to breast cancer would be obtained from a randomised controlled trial in
      which exposure to dietary fat intake was systematically varied. A limitation of
      randomised controlled trials of breast cancer prevention, however, is the large
      sample size required to detect plausible reductions in risk resulting from the
      intervention. We describe here experience over a period of 9 years with the use
      of one risk factor for breast cancer as a criterion for entry to a clinical trial
      of breast cancer prevention. The risk factor used was the presence of extensive
      densities in the breast tissue on mammography, which has been found by several
      investigators to be strongly associated with risk of breast cancer. Using this
      criterion for selection, 1800 subjects of mean age 46 years were enrolled between
      1982 and 1986, and again between 1988 and the present. Throughout this period,
      the point estimate of annual invasive cancer incidence was approximately 6 per
      1000 per year. The observed cancer incidence has been consistently 4-5 times the
      incidence expected from age-specific breast cancer incidence data for women
      living in Ontario. These data show that the selection of subjects for a clinical
      trial of breast cancer prevention using the criterion of extensive breast
      parenchymal densities does identify a group at substantially increased risk of
      breast cancer. Use of this criterion for the selection of subjects can
      substantially reduce the sample size required for a clinical trial of a
      preventive strategy.

PMID- 7640236
TI  - The short-term and long-term effect of a pregnancy on breast cancer risk: a
      prospective study of 802,457 parous Norwegian women.
AB  - Time-related effects of a pregnancy on breast cancer risk were examined in a
      population-based prospective study of 802,457 parous Norwegian women aged 20-56
      years. The mean follow-up time was 16.4 years. A total of 4787 women were
      diagnosed with breast cancer. We observed a short-term increase in risk of breast
      cancer after a full-term pregnancy, with a maximum 3-4 years after delivery,
      followed by a long-lasting decrease in risk. The maximum risk was about twice the
      risk for women whose last delivery was 20 or more years previously (incidence
      rate ratio = 1.99, 95% confidence interval = 1.70-2.33). Compared with
      nulliparous women, those with one or two children were at higher risk in the
      first decade after the last pregnancy, whereas those with three or more children
      were at lower risk in most categories of time since the last birth. The positive
      association between breast cancer risk and age at last birth was markedly reduced
      after adjustment for time since last birth. We conclude that there is a non
      linear relationship between breast cancer incidence and time since last birth.
      Part of the relation with age at last birth may be attributed to the association
      with time since last birth.

PMID- 7640237
TI  - Recent trends in incidence of and mortality from breast, ovarian and endometrial
      cancers in England and Wales and their relation to changing fertility and oral
      contraceptive use.
AB  - Reproductive-related factors play a major role in the aetiology of cancers of the
      breast, ovary and endometrium. Pregnancy history influences the risk of each of
      these cancers, and oral contraceptive use modifies the risks of ovarian and
      endometrial cancers, although its effect on breast cancer risk is less certain.
      We analysed recent time trends in the incidence and mortality of these cancers in
      England and Wales and assessed whether they can be explained by changes in
      fertility and oral contraceptive use. During 1962-87, there were significant
      increases in the overall incidence of breast cancer (0.95% increase per annum)
      and ovarian cancer (0.76% per annum) but little increase in endometrial cancer
      (0.13% per annum). At young ages incidence of each of the cancers has declined in
      recent years, whereas at older ages there have been substantial increases.
      Mortality data show similar time trends. In analyses by birth cohort, incidence
      of each of the cancers increased steeply for successive cohorts born before the
      turn of the century, and more slowly for cohorts thereafter, reaching a maximum
      for those born in the 1920s, and decreased for those born subsequently. The
      increases in incidence for women born before the turn of the century paralleled
      marked declines in their fertility. The fall in risk for women born after the
      1920s was not accompanied by significant increases in their fertility, but
      coincided with the introduction and increase in use of oral contraceptives. For
      ovarian and endometrial cancers this accords with strong evidence from person
      based studies of the protective effect of oral contraceptives. For breast cancer,
      the reasons for the recent decline are not clear. It would accord with recent
      suggestions of a long-term protective effect of oral contraceptives, on which
      further studies are needed. It is also possible, however, that changes in other
      risk factors such as dietary fat intake and menarcheal age might have contributed
      to the recent declines in the risk of these cancers.

PMID- 7640238
TI  - Trends in breast cancer mortality among Swedish women 1953-92: analyses by age,
      period and birth cohort.
AB  - Trends in breast cancer mortality among Swedish women were explored on the basis
      of all 51,048 deaths in women 30-89 years of age in Sweden during the period 1953
      92. The age-standardised mortality rates were virtually unchanged during the
      observation period (with a mean of 32 deaths per 100,000 females and year), as
      were age-specific rates. In age-period-cohort analyses, age alone explained
      almost all of the variation in the rates. The effects of period and cohort were
      statistically significant, but very modest. Cohort effects seemed to explain more
      than period effects, and a weak downward trend starting with women born in 1883
      92 was noted. A change in 1981 in the policy to classify the causes of death from
      the death certificates seemed to entail an artificial lowering of the mortality
      rates in women older than 75 years. It is concluded that breast cancer mortality
      in Sweden during the last 40 years has been remarkably stable, in spite of a
      substantial and constant increase in the incidence. This divergence between
      mortality and incidence reflects improved survival, which could in part be
      explained by earlier detection and more efficient treatment, or by an increasing
      occurrence of less aggressive tumours.

PMID- 7640239
TI  - Efficiency of organised and opportunistic cytological screening for cancer in
      situ of the cervix.
AB  - Cervical cancer incidence and mortality can be reduced by removal of precursor
      lesions detected at cytological screening. Organised screening, i.e. regular
      invitation of defined target groups, is generally considered more effective than
      opportunistic screening. The latter method however, is predominant in most
      settings. There is no scientific basis for advocating one type of screening or
      the other. Our aim was to compare the two types and to analyse their efficiency.
      We analysed 466,275 smears taken in an open cohort of 118,890 women during 1969
      88. A computerised database permitted standardised classification of all smears
      and complete ascertainment of cancer in situ through record linkage. The number
      of in situ cancers detected per 1000 smears, the detection ratio, was used as an
      outcome measure both in univariate analyses and in multivariate logistic
      regression models. Cancer in situ was detected in 1076 women in the study cohort,
      with a detection ratio of 3.0 at organised and 2.1 at opportunistic screening,
      yielding an unadjusted odds ratio of 0.69 (95% CI 0.61-0.79). After adjustment
      for age and time period, the probability of detecting cancer in situ was around
      25% higher with opportunistic than with organised screening (OR = 1.26; 95% CI
      1.09-1.46). This difference in favour of opportunistic screening was most
      pronounced in the first 10 year period and disappeared during the last decade.
      The difference in efficiency between organised and opportunistic screening in the
      detection of cancer in situ was slight, if any. The dogma that organised
      screening is significantly more efficient than the opportunistic type needs
      reconsideration.

PMID- 7640240
TI  - Limitations of the death certificate only index as a measure of incompleteness of
      cancer registration.
AB  - The death certificate only (DCO) index, which quantifies the proportion of
      patients for whom the death certificate provides the only notification to the
      registry, is a widely used measure of incompleteness of population-based cancer
      registration. This paper provides an algebraic assessment and a quantitative
      illustration of the relationship between the DCO index and incompleteness of
      cancer registration. It is shown that the relationship between the DCO index and
      incompleteness of registration is strongly dependent on the case fatality rate
      and the misclassification rates of cancer deaths among unregistered patients.
      Therefore, the DCO index is a very poor indicator of incompleteness. Similar
      limitations apply to the DCN index (proportion of cases first notified by death
      certificate), which has been proposed as an alternative measure of
      incompleteness.

PMID- 7640242
TI  - [Cycles of paintings in magnificent color by an adult woman with Down syndrome].

PMID- 7640241
TI  - Review of survival analyses published in cancer journals.
AB  - Survival analysis has found widespread applications in medicine in the last 10-15
      years. However, there has been no published review of the use and presentation of
      survival analyses. We have carried out a systematic review of the research papers
      published between October and December 1991 in five clinical oncology journals. A
      total of 132 papers were reviewed. We looked at several aspects of study design,
      data handling, analysis and presentation of the results. We found that almost
      half of the papers did not give any summary of length of follow-up; that in 62%
      of papers at least one end point was not clearly defined; and that both logrank
      and multivariate analyses were frequently reported at most only as P-values
      [63/84 (75%) and 22/47 (47%) respectively]. Furthermore, although many studies
      were small, uncertainty of the estimates was rarely indicated [in 13/84 (15%)
      logrank and 16/47 (34%) multivariate results]. The procedure for categorisation
      of continuous variables in logrank analyses was explained in only 8/49 (16%)
      papers. The quality of graphs was felt to be poor in 43/117 (37%) papers which
      included at least one survival curve. To address some of the presentational
      inadequacies found in this review we include new suggested guidelines for the
      presentation of survival analyses in medical journals. These would complement the
      statistical guidelines recommended by several clinical oncology journals.

PMID- 7640243
TI  - [Developing nursing standards. Report on the assembling and engaging of a working
      group for the establishment of nursing standards at the Pediatric
      Department/Pediatric Nursing Center of the Tubingen University Hospital].

PMID- 7640244
TI  - [Burns--seen not only from a medical viewpoint].

PMID- 7640245
TI  - [The child with partial hearing loss. 2. Treatment of partial hearing loss].

PMID- 7640246
TI  - [Sunrise in a foreign language. Experiences of a deaf patient after cochlea
      implantation].

PMID- 7640247
TI  - [Care planning for a premature infant].

PMID- 7640248
TI  - [Ambulatory surgery. The German Association for Medical Legislation passed
      recommendations].

PMID- 7640249
TI  - ["Initiative Babyfriendly Hospital" of the WHO and UNICEF].

PMID- 7640250
TI  - An investigation to estimate the fluoride uptake adjacent to a fluoride-releasing
      bonding agent.
AB  - Decalcification of the teeth remains a problem during orthodontic treatment with
      fixed appliances. It has been suggested that bonding agents which release
      fluoride could supply it to the area of the tooth most at risk from
      decalcification. The aim of this study was to estimate uptake by enamel adjacent
      to a fluoride releasing bonding agent. Acid etch biopsies were used to estimate
      the concentration of fluoride in enamel adjacent to brackets bonded with
      Vitrabond and Geristore. Results indicate that there was a significant increase
      in the concentration of fluoride in enamel adjacent to Vitrabond. The clinical
      significance of the increase in the concentration of fluoride adjacent to
      Vitrabond and the mechanism by which fluoride moves from the material into the
      enamel remain unclear.

PMID- 7640251
TI  - Long-term effects of the Herbst appliance on the dental arches and arch
      relationships: a biometric study.
AB  - The purpose of this study was to evaluate biometrically the treatment and post
      treatment effects of the Herbst appliance on the dental arches and arch
      relationships. The sample consisted of 53 Class II, division 1 malocclusion
      patients (33 boys and 20 girls) treated with the Herbst appliance. The mean age
      of the patients before treatment was 12.5 years (SD = 1.2 years). Dental casts
      were analysed before treatment, after treatment, 6 months post-treatment and at
      the end of the growth period (5-10 years post-treatment). The following variables
      were assessed: sagittal molar and canine relationships, overjet, overbite,
      maxillary and mandibular arch perimeters, and inter-molar and inter-canine dental
      arch widths. During treatment, the overjet, overbite, and sagittal molar
      relationship were overcorrected in most of the cases, while the sagittal canine
      relationship was normalized. The maxillary and mandibular arch perimeters
      increased during treatment, as did dental arch widths (molar and canine). In the
      long-term (mean = 6.7 years after treatment), Herbst appliance treatment resulted
      in a normal or over-corrected sagittal molar relationship in 79 per cent and a
      normal canine relationship in 68 per cent of the cases. Eighty-three per cent of
      the subjects had an overjet of 4.5 mm or less. In the long-term, the arch
      perimeters seemed to follow a normal dental development pattern. The increase of
      the upper molar and canine dental arch widths during treatment remained virtually
      stable whilst the lower intermolar arch widths seemed unaffected by treatment.

PMID- 7640252
TI  - Chernoff faces: an orthodontic application.
AB  - This retrospective study examined 21 children (12 males and nine females) with
      Class III malocclusions, who had been successfully treated by a non-extraction
      technique and for whom follow-up records were available at least 2 years after
      all treatment and retention had ceased. On the basis of their post-retention
      records, children were divided into two groups: those who remained stable (n =
      10) and those whose treatment relapsed (n = 11). A graphical technique of data
      description, Chernoff faces, in which variables for each individual may be
      portrayed by appropriate scaling of selected facial features, was used to
      construct cartoon faces for each child. Seven variables, overjet, overbite, upper
      and lower incisor inclination, the numbers of anterior and posterior teeth in
      lingual occlusion and the angle ANB were chosen and diagrammatic faces drawn
      using data from both the start of treatment and post-retention stages. These were
      arranged according to relapse status and scrutinized to determine whether the
      groups possessed any common features which were related to the outcome of
      treatment. The faces showed a wide range of variation, especially at the
      pretreatment stage. Whilst the cartoons were easy to read, no typical features
      could be identified at the start of treatment which might indicate that therapy
      would later relapse.

PMID- 7640253
TI  - The ex vivo effect of ligation technique on the static frictional resistance of
      stainless steel brackets and archwires.
AB  - This ex vivo investigation compared the effect of various orthodontic ligation
      techniques on the static frictional resistance of stainless steel brackets and
      archwires under both dry and wet conditions. The techniques studied were:
      elastomeric modules tied conventionally and in a 'figure of 8' pattern, stainless
      steel ligatures, and Teflon-coated ligatures. The first part of the investigation
      involved the construction of calibration curves for each of the materials, so an
      estimate of the normal force exerted by the ligatures could be ascertained.
      Secondly, a pair of ligature locking pliers were modified so that ligatures could
      be placed with a standardized force. Finally, the four methods of ligation were
      directly compared on a specially constructed testing apparatus. Results revealed
      that elastomeric modules tied in a 'figure of 8' pattern produced significantly
      more friction than any other method tested, under both dry and wet conditions. No
      significant differences in frictional resistance were found between
      conventionally tied elastomeric modules and stainless steel ligatures. Teflon
      coated ligatures, however, were associated with the lowest frictional forces. The
      results of the calibration tests indicated that the normal forces exerted by all
      four methods of ligation may be higher than previously estimated.

PMID- 7640254
TI  - The effects of archwire forces on incisor intrusion.
AB  - The forces exerted by archwires were measured in association with both Begg and
      Straight-Wire attachments. Seven stainless steel and three nickel-titanium wires
      were tested at vertical deflections equivalent to 20, 30, and 40 degrees, these
      being incorporated via anchor bends or reverse curve of Spee as appropriate to
      each system. All seven brands of stainless steel arches demonstrated similar
      performance. An increase in archwire diameter from 0.016 to 0.018 inch increased
      intrusive forces by 64 per cent for stainless steel and 58 per cent for nickel
      titanium. Increasing anchor bend or reverse curve of Spee produced considerable
      force increases across the range of specimens. Begg archforms produced more force
      than Straight-Wire archforms of similar deflection when attached to molars only.
      Attachment of archwires to second premolars in addition to molars reduced the
      intrusive forces produced by Begg arches, but increased the forces of Straight
      Wire arches.

PMID- 7640255
TI  - The effect of sandblasting on the retention of first molar orthodontic bands
      cemented with glass ionomer cement.
AB  - This study examined the effect of sandblasting, in vitro, on the bond strength
      and survival time of first molar orthodontic bands. Survival time was assessed
      following simulated mechanical fatigue in a ball mill. The amount of cement left
      attached to the band after debanding was also assessed. In addition, the effect
      of sandblasting on the failure rate of 320 first molar bands cemented in 107
      patients was examined in a half-mouth trial. Ketac-cem, mixed according to
      manufacturers' instructions was used as the luting agent for both laboratory and
      clinical trials. In vitro, sandblasting increased bond strength by 27 per cent (P
      < 0.01) and produced a three-fold increase in the median survival time relative
      to the untreated sample (P < 0.001) in the ball mill experiment. Sandblasting
      resulted in more cement remaining on the band rather than on the tooth enamel
      after band removal. In vivo, sandblasting reduced the clinical failure rate of
      the first molar bands (P < 0.001).

PMID- 7640256
TI  - Long-term evaluation of treated class II division 1 malocclusions utilizing the
      PAR index.
AB  - The PAR Index was used to evaluate treatment and long-term post-retention results
      obtained from 50 Class II division 1 malocclusions. Dental casts were used to
      record the occlusions pre- and post-treatment, as well as 1 and 10 years post
      retention. The results suggested a high treatment standard, as indicated by mean
      percentage PAR score reduction. However, maintenance of post-treatment results 1
      and 10 years post-retention was only achieved in 60 and 38 per cent of cases,
      respectively. The major factor involved in this deterioration appeared to be late
      lower anterior crowding.

PMID- 7640257
TI  - Pneumosinus dilatans of the ethmoid sinus--incidental finding on a cephalometric
      radiograph.
AB  - A case of pneumosinus dilatans of the posterior ethmoidal region is presented.
      The condition known as pneumosinus dilatans is discussed, as are accessory
      ethmoidal air cells with respect to their most common localization and
      radiographic appearance. The diagnostic imaging features of this condition are
      described and a recommendation of views to adequately delineate this disorder are
      given. The importance of an adequate and thorough review of the cephalometric
      radiograph for pathologic conditions is stressed.

PMID- 7640258
TI  - Partial glossectomy for the treatment of anterior open bite. A case report.
AB  - A 24-year-old Afro-Caribbean with a pronounced anterior open bite and bimaxillary
      protrusion was successfully treated to a stable result with a partial glossectomy
      and fixed appliance therapy. Although transient sialorrhea and paraesthesia were
      experienced post-operatively, speech and function showed some improvement 2 years
      after treatment.

PMID- 7640259
TI  - Customized jig for a bonded palatal retainer: a case report.
AB  - The construction of a customized jig to assist with the placement of multiple
      multistranded wire retainers is described and illustrated. Its use in a patient
      with severe resorption of the roots and surrounding alveolar bone of the upper
      anterior teeth is reported.

PMID- 7640260
TI  - The split Tru-tain: a simple answer to a common problem.
AB  - A cheap and easy to wear alternative to the Barrer appliance is described. This
      appliance can be used in either jaw for the treatment of very mild malocclusions,
      the correction of post-treatment relapse or as a retainer where minor changes are
      desirable after the removal of fixed appliances.

PMID- 7640261
TI  - Orthodontic facebow injuries.

PMID- 7640262
TI  - Re: obtaining data from patient records.

PMID- 7640263
TI  - Orthodontics in Romania. A visit to Bucharest, June 1994.

PMID- 7640264
TI  - Proton sharing between cysteine thiols in Escherichia coli thioredoxin:
      implications for the mechanism of protein disulfide reduction.
AB  - Proton sharing between acidic groups has been observed in the active sites of
      several enzymes, including bacteriorhodopsin, aspartic proteases, and
      ribonuclease HI. We here report NMR observations suggestive of proton sharing
      between cysteine thiols in the active site of the oxidation-reduction enzyme
      thioredoxin. The pKas of the two cysteine thiols in the Escherichia coli protein
      are removed from the expected value of 8.4 by approximately 1 pH unit in either
      direction, upward and downward. Further, the C beta resonances of both residues
      show clearly the effects of both of these pKas, indicating that the titrations of
      the two thiol groups are intimately linked. This behavior strongly suggests that
      the low pKa ascribed to the deprotonation of the Cys 32 thiol most likely arises
      through the interaction and close approach of the thiol of Cys 35, with the
      thiolate anion of Cys 32 stabilized through the sharing of the remaining thiol
      proton, nominally attached to Cys 35. These observations provide a rationale for
      the mediation of active site pH control, an important aspect of the mechanism of
      thioredoxin and other proteins with catalytic thioredoxin domains, such as
      protein disulfide isomerases.

PMID- 7640265
TI  - Dynamic interactions of rabbit liver cytochromes P450IA2 and P450IIB4 with
      cytochrome b5 and NADPH-cytochrome P450 reductase in proteoliposomes.
AB  - Purified liver microsomal cytochrome P450IA2 or P450IIB4 was co-reconstituted
      with cytochrome b5 or NADPH-cytochrome P450 reductase in phosphatidylcholine
      phosphatidylethanolamine-phosphatidylserine vesicles at a lipid to P450 weight
      ratio of 2 by cholate dialysis procedures. The proteoliposomes catalyzed drug
      oxidation. Rotational diffusion of cytochrome P450 was measured by observing the
      decay of absorption anisotropy, r(t), after photolysis of the heme.CO complex.
      Analysis of r(t) was based on a "rotation-about-membrane normal" model. The
      absorption anisotropy decayed within 1 ms to a time-independent value, r3.
      Different rotational mobility for the two cytochrome P450s was observed. Though
      20% of cytochrome P450IA2 was immobile, all cytochrome P450IIB4 molecules were
      rotating. The rotational relaxation time, phi, of the mobile population was 237
      microseconds for cytochrome P450IA2 and 160 microseconds for cytochrome P450IIB4.
      The two cytochrome P450s have shown very different interactions with cytochrome
      b5 and NADPH-cytochrome P450 reductase. By the presence of the redox partner, the
      mobile population of cytochrome P450IA2 was increased significantly from 80% to
      96% (plus cytochrome b5) and to 89% (plus NADPH-cytochrome P450 reductase) due to
      dissociation of P450 oligomers. On the other hand, the mobility of cytochrome
      P450IIB4 was not considerably affected by the presence of cytochrome b5 or NADPH
      cytochrome P450 reductase as judged by little difference in phi and r3, keeping
      the mobile population of 100%. These results imply that cytochrome P450IA2 forms
      a transient association with cytochrome b5 and NADPH-cytochrome P450
      reductase.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7640266
TI  - Fusion of proteolyzed low-density lipoprotein in the fluid phase: a novel
      mechanism generating atherogenic lipoprotein particles.
AB  - During atherogenesis, lipid droplets appear in the extracellular space of the
      arterial intima. We previously observed generation of lipid droplets on the
      surface of exocytosed mast cell granules when granule neutral proteases degraded
      the granule-bound LDL particles and the particles became unstable and fused
      [Kovanen, P.T., & Kokkonen, J.O. (1991) J. Biol. Chem. 266, 4430-4436]. We have
      now extended our studies to the fluid phase and examined the effects of several
      proteases (trypsin, alpha-chymotrypsin, Pronase, plasmin, kallikrein, and
      thrombin) all known for their ability to cleave the apolipoprotein B-100
      component (apoB-100) of LDL. The fused LDL particles were separated from unfused
      particles by gel filtration or by density gradient ultracentrifugation.
      Proteolytic degradation of LDL with trypsin, alpha-chymotrypsin, or Pronase led
      to fragmentation of apoB-100 and release of the fragments from the LDL particles
      and triggered particle fusion. In contrast, proteolytic degradation of LDL with
      plasmin, kallikrein, or thrombin, which also led to fragmentation of apoB-100 but
      not to release of fragments, did not trigger particle fusion. With advancing
      degradation of apoB-100, particles having progressively lower densities and
      larger sizes were generated. Thus, after incubation for 24 h with alpha
      chymotrypsin (apoB-100:alpha-chymotrypsin mass ratio 10:1) 40% of the apoB-100
      was degraded and about 30% of the LDL particles had fused and reached diameters
      of up to 70 nm and densities ranging from 1.020 to < 1.005 g/mL. When the
      proteolyzed LDL particles, both unfused and fused, were incubated with
      macrophages, only those particles that had undergone fusion were ingested and
      converted into intracellular cholesteryl ester droplets. Thus proteolysis of LDL
      with release of apoB-100 fragments renders the particles sufficiently unstable to
      fuse and thus to become liable to ingestion by macrophages. Since the fused LDL
      particles resemble the extracellular lipid droplets in the atherosclerotic
      arterial intima and generate foam cells in vitro, these findings support the idea
      that proteolytic fusion of LDL is an atherogenic process.

PMID- 7640267
TI  - Non-A beta component of Alzheimer's disease amyloid (NAC) is amyloidogenic.
AB  - The non-A beta component of Alzheimer's disease (AD) amyloid (NAC) was identified
      biochemically as the second major component in the amyloid purified from brain
      tissue of AD patients. NAC, derived from its 140 amino acid long precursor, NACP,
      is at least 35 amino acids long (NAC35) although its amino terminus is not
      definitely determined. An antiserum, anti-NAC-X1, was raised against the amino
      terminal 9 amino acid sequence of NAC35 and purified on a peptide affinity
      column. This affinity-purified anti-NAC-X1 antibody immunostained amyloid in AD
      brain sections and recognized NAC35 but not NACP on Western or dot blot. In
      aqueous solutions, synthetic NAC35 self-aggregated in a time-, concentration-,
      and temperature-dependent manner. NAC35 was detected initially as a monomer with
      a molecular mass of 3500 Da but became aggregated as a function of time into a
      higher molecular mass component that could not migrate into the gel. The
      aggregate of NAC35 showed green-gold birefringence after Congo red staining when
      analyzed under polarized light and fiber-like structure when analyzed
      ultrastructurally. These results suggest that NAC can form amyloid after it has
      been cleaved out of its precursor and may be a crucial factor in amyloidosis in
      the AD brain.

PMID- 7640268
TI  - Identification of the active site catalytic residue in human isovaleryl-CoA
      dehydrogenase.
AB  - Isovaleryl-CoA dehydrogenase (IVD) is a homotetrameric flavoenzyme which
      catalyzes the conversion of isovaleryl-CoA to 3-methylcrotonyl-CoA. E376 of pig
      medium chain acyl-CoA dehydrogenase (MCAD), a homologous enzyme, has been
      identified as the active site catalytic residue. Amino acid sequence alignment
      shows that A375 is the corresponding residue in human IVD. Using the atomic
      coordinates determined for MCAD, molecular modeling suggests that E254 is the
      substituting catalytic residue in IVD. To substantiate the importance of this
      residue for enzyme function, cDNAs for the wild-type human IVD and E254G, E254D,
      E254Q, and E254G/A375E mutant IVDs were constructed and cloned into a prokaryotic
      expression vector. The proteins were synthesized in Escherichia coli and
      purified, and their properties were examined. The catalytic activity of the
      recombinant wild-type IVD was the highest in the presence of isovaleryl-CoA, and
      its UV/visible light spectrum in the presence of isovaleryl-CoA showed quenching
      of its characteristic absorption in the 445-nm region and appearance of
      absorption at 600 nm. The E254G and E254Q mutant IVDs had no detectable enzymatic
      activity, and isovaleryl-CoA did not induce quenching of the absorption in the
      445-nm region or the appearance of absorption at 600 nm. The E254D mutant IVD had
      residual activity for isovaleryl-CoA, and its spectrum was altered compared to
      that of the wild type. The E254G/A375E mutant IVD exhibited catalytic activity
      toward isovaleryl-CoA, and its spectrum in the absence or presence of the
      substrate was similar to that of the wild-type IVD.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7640269
TI  - Thermodynamics of inhibitor binding to mutant forms of glucoamylase from
      Aspergillus niger determined by isothermal titration calorimetry.
AB  - We have investigated the binding of mutant forms of glucoamylase from Aspergillus
      niger to the inhibitors 1-deoxynojirimycin and acarbose. The mutants studied
      comprise a group of single amino acid replacements in conserved regions near the
      active site of the enzyme. For each mutant we have determined both the affinities
      for the two inhibitors and the thermodynamic state functions for binding using
      titration microcalorimetry. We find that acarbose binds to all the mutants with a
      wide range of binding constants (10(4) < Ka < 10(13) M-1). In contrast, 1
      deoxynojirimycin shows either binding at near wild-type affinity (Ka
      approximately equal to 10(4) M-1) or no detectable binding. The changes in the
      affinities of the mutant enzymes are rationalized in terms of the known three
      dimensional structure of the wild-type enzyme with subsites 1, 2, and 3 being
      important for acarbose binding while only subsite 1 is critical for 1
      deoxynojirimycin binding. In most of the mutants studied the magnitudes of the
      enthalpies and the entropies of binding of the mutant enzymes differed from those
      of the wild-type enzyme with the mutant enzymes having a relatively large portion
      of their binding energy composed of enthalpy and a relatively small proportion
      composed of entropy. The pattern of changes in the enthalpy and entropy is
      hypothesized to be due to changes in the structural complementarity of the
      binding pocket and the inhibitor.

PMID- 7640270
TI  - Mutational analysis of the roles in catalysis and substrate recognition of
      arginines 54 and 305, aspartic acid 309, and tryptophan 317 located at subsites 1
      and 2 in glucoamylase from Aspergillus niger.
AB  - The mutants Arg54-->Leu, Arg54-->Lys, Arg305-->Lys, Asp309-->Glu, and Trp317-
      >Phe, located at subsites 1 and 2 in glucoamylase from Aspergillus niger, provide
      insight into the importance of specific hydrogen bonds and hydrophobic
      interactions in substrate recognition, catalytic mechanism, and stability. As
      suggested from the crystal structure of a closely related glucoamylase [Aleshin,
      A. E., Firsov, L. M., & Honzatko, R. B. (1994) J. Biol. Chem. 269, 15631-15639],
      Arg54 in subsite 1 hydrogen bonds to the key polar group 4'-OH of maltose. The
      two mutants of Arg54 display losses in transition-state stabilization of 16-21 kJ
      mol-1 in the hydrolysis of different maltooligodextrins, which originate from a
      [(1.2-1.8) x 10(3)]-fold reduction in kcat and changes in Km ranging from 25% to
      300% of the wild-type values. Arg305 similarly hydrogen bonds to 2'-OH and 3-OH,
      located at subsites 1 and 2, respectively. Arg305-->Lys glucoamylase is not
      saturated at concentrations of maltose or maltoheptaose of 400- and 40-fold,
      respectively, the Km of the wild-type enzyme. This mutant also has highly reduced
      kcat. On the other hand, for the alpha-1,6-linked isomaltose, the Lys305 mutant
      surprisingly has the same Km as the wild-type enzyme, while kcat is 10(3)-fold
      reduced. Arg305 is thus an important determinant in the distinction of the alpha
      1,4 to alpha-1,6 substrate specificity. Arg305 interacts electrostatically and
      hydrophobically with the side chains of Asp309 and Trp317.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7640271
TI  - Structural and electronic factors that influence oxygen affinities: a
      spectroscopic comparison of ferrous and cobaltous oxymyoglobin.
AB  - Various structural and electronic factors that result in similar rates of oxygen
      association (kon) and differing rates of oxygen dissociation (koff) for ferrous
      (FeMb) and cobaltous (CoMb) myoglobin have been investigated. Similar values for
      kon indicate similar barriers to oxygen binding for CoMb and FeMb. Through
      optical spectroscopy, we have found that the stable quantum yields of photolysis
      for CoMbO2 (0.55 +/- 0.05) and FeMbO2 (0.50 +/- 0.05) at 10 K are the same. The X
      ray absorption near edge spectra (XANES) of CoMb and FeMb reveal similar metal
      heme displacements for the deoxy, oxy, and low temperature photoproduct states of
      CoMb and FeMb. Thus, similar barriers to ligand binding, indicated by similar
      kon's and photoproduct yields for CoMb and FeMb, correlate with the metal-heme
      displacements for the oxy, deoxy, and low temperature photoproduct states of CoMb
      and FeMb. Lower values of koff for FeMbO2 versus CoMbO2 imply different barriers
      to oxygen release for the two species. X-ray edge positions of CoMb and FeMb
      indicate a substantial transfer of electron density from the metal to the ligand
      upon oxygenation. The distribution of electron density throughout the M-O-O
      moiety differs for CoMbO2 and FeMbO2. Resonance Raman spectroscopy has
      demonstrated that the Co-O bond is weaker when compared to Fe-O [Tsubaki, M., &
      Yu, N. T. (1981) Proc. Natl. Acad. Sci., U.S.A. 78, 3581]. We have used
      photolyzed/unphotolyzed Fourier Transform Infrared (FTIR) difference spectra of
      CoMb16O2, CoMb18O2, FeMb16O2, and FeMb18O2 to show that the dioxygen stretching
      frequency, v(O-O), in CoMbO2 (approximately 1138 cm-1) is higher than FeMbO2
      (approximately 1131 cm-1). The dioxygen stretching frequency in CoMbO2 is closer
      to that of heme protein models lacking a hydrogen bond to the distal histidine,
      suggesting that formation of the hydrogen bond in FeMbO2 provides a greater
      effect on the distribution of electron density throughout the Fe-O-O... HN
      moiety, potentially stabilizing a more ionic Fe-O-O bond. These findings
      demonstrate important electrostatic differences in the distal environments of
      CoMbO2 and FeMbO2, resulting in different barriers to oxygen release.

PMID- 7640272
TI  - Evidence for two distinct azurins in Alcaligenes xylosoxidans (NCIMB 11015):
      potential electron donors to nitrite reductase.
AB  - We have isolated two type 1 copper-containing proteins (M(r) approximately 13K)
      from Alcaligenes xylosoxidans (NCIMB 11015) grown under denitrifying conditions.
      Amino acid sequence analysis of these two proteins shows one to be the previously
      identified azurin (Ambler, 1971), which we shall call azurin I, and the other to
      be a related, but previously undescribed, blue copper protein which we show to
      also be an azurin and propose to call azurin II. Thus, NCIMB 11015 becomes the
      second system where two distinct azurins are found, the other being Methylomonas
      J (Ambler & Tobari, 1989). On isoelectric focusing, azurin I migrates very
      similarly to the previously identified azurin from this organism while azurin II
      migrates similarly to azurin purified from Alcaligenes denitrificans NCTC 8582.
      The sequence of azurin II is 33% different than the azurin I sequence but is only
      11% different than the azurin from Alcaligenes denitrificans NCTC 8582. Optical
      spectra for the two proteins are very similar with epsilon mM values of 6.27 and
      5.73 mM-1 cm-1 for azurin I and II, respectively, at lambda max approximately 620
      nm. The 291 nm shoulder normally ascribed to the hydrophobic nature of tryptophan
      48 is clearly observed in azurin I but is missing in azurin II. Amino acid
      analysis confirms that this tryptophan is missing in azurin II. Azurin I and
      azurin II show essentially the same redox potential of 305 +/- 10 mV at pH 7.5
      and are equally effective electron donors to the purified dissimilatory nitrite
      reductase of Alc. xylosoxidans in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7640273
TI  - Effects of base analog substitutions in the noncoding dC of the 3'-d(CTG)-5'
      template recognition site of the bacteriophage T7 primase.
AB  - The 63-kDa gene 4 protein (DNA primase) of bacteriophage T7 catalyzes the
      synthesis of the oligoribonucleotides pppACC(C/A) and pppACAC at single-stranded
      DNA recognition sites 3'-d[CTGG-(G/T)]-5' and 3'-d(CTGTG)-5', respectively. At
      these sites, the 3'-terminal deoxycytidine residue is conserved but noncoding;
      the 3'-dC residue is required to initiate catalytic synthesis of
      oligoribonucleotides, yet it is not used as a template residue for the synthesis
      of a complementary G residue in the RNA primer. We have examined the interactions
      between T7 primase and the functional groups of the 3'-dC residue by measuring
      the ability of the primase to catalyze the synthesis of oligoribonucleotides on
      synthetic single-stranded 20-mer templates [e.g., 3'-d(GCTATGGTGACTGGTAGTCG)-5']
      that contain analogs of dC in the conserved pentanucleotide recognition site.
      Recognition sites containing 5-methyldeoxycytidine (m5dC) or 1-(beta-D-2'
      deoxyribosyl)-2-pyrimidinone (dH4C) substitutions for dC support
      oligoribonucleotide synthesis whereas those containing deoxythymidine (dT) and
      deoxyuridine (dU) substitutions do not. Oligoribonucleotide synthesis on the
      native template (containing dC) is inhibited competitively by the template
      containing a dT residue in the primase recognition site, 3'-[(N10)TTGGT(N5)]-5',
      with an apparent Ki of 1.30 +/- 0.04 microM. Templates containing dU residues, 3'
      [(N10)UTGGT(N5)]-5' and 3'-[(N9)UTTGGT-(N5)]-5', affect both the apparent Km and
      Vmax parameters for oligoribonucleotide synthesis on the 3'-[(N10)CTGGT(N5)]-5'
      template.

PMID- 7640274
TI  - Uptake and processing of duplex DNA by RecA nucleoprotein filaments: insights
      provided by a mixed population of dynamic and static intermediates.
AB  - In the polarized strand exchange that is promoted by Escherichia coli RecA
      protein, when the initiating end of a duplex DNA molecule is blocked by
      heterology, the homologous distal end nonetheless forms a joint with single
      stranded DNA, but strand exchange in that joint cannot be completed because the
      strand that would otherwise be displaced lacks a free 5' end. Instead, 2/3 to 3/4
      of such distal joints cyclically form and dissociate. Dissociation requires the
      hydrolysis of ATP (Burnett et al., 1994). Observations on DNase protection
      revealed that consistent with their dynamic nature, these joints were
      heterogeneous in length, extending from the labeled distal end of the duplex up
      to 600 base pairs within the homologous region. Switching of base pairs was
      undetectable in this fraction of distal joints. However, the other 1/3 to 1/4 of
      distal joints, which did not cycle, were as long as the entire homologous region
      (6 kb), and underwent complete switching of base pairs. The formation of these
      static joints occurred at a rate in excess of 100 bp per second, without
      requiring hydrolysis of ATP. These and earlier observations suggest that the RecA
      filament containing single-stranded DNA rapidly incorporates duplex DNA into a
      coaxial three-stranded helix by a passive process, whereas additional energy is
      required to convert the three-stranded intermediate into products or back into
      substrates, both of which involve the unwinding of many turns of three-stranded
      helix.

PMID- 7640275
TI  - Characterization of Mg(2+)-dependent 3'-processing activity for human
      immunodeficiency virus type 1 integrase in vitro: real-time kinetic studies using
      fluorescence resonance energy transfer.
AB  - Human immunodeficiency virus type 1 integrase (HIV-1 IN) catalyzes the
      integration of HIV-1 DNA into the host chromosome. In vitro reactions with
      endogenous viral DNA require Mg2+ as the metal cofactor, whereas in vitro studies
      performed with short oligonucleotide substrates utilize Mn2+. In this study, we
      report that the donor processing activity of HIV-1 IN alters depending on the
      structure and length of the oligonucleotide substrates. Increases in the length
      of the substrate cause alterations in the efficiency of Mg(2+)-dependent donor
      processing activity, thereby reconciling this discrepancy between the in vivo and
      in vitro HIV-1 IN mediated reactions. We have also found that the 3'-processing
      activity of HIV-IN is responsible for cleaving the junction between the viral and
      target sequences of the recombination intermediate. Its mechanism differs from
      the previously described disintegration reaction in that the donor strands are
      regenerated without a joining reaction of the target strands. Kinetic studies of
      3'-processing activity suggest that the kcat (0.24/h) is very low. This implies
      that HIV-1 IN remains as a complex with the processed DNA prior to the strand
      transfer reaction.

PMID- 7640276
TI  - Substrate-length-dependent activities of human immunodeficiency virus type 1
      integrase in vitro: differential DNA binding affinities associated with different
      lengths of substrates.
AB  - Human immunodeficiency virus type 1 integrase (HIV-IN) is an enzyme essential for
      the integration of viral DNA into the host chromosome, a process that is an
      attractive target for drug development. In vitro assays have been developed to
      study both components of the integration process, the 3'-processing and strand
      transfer reactions. However, major discrepancies between results obtained from in
      vivo and in vitro events raise concerns as to the biological relevance of
      activities observed in vitro. These discrepancies include the size of the
      substrate and the nature of the divalent cation used. In this study, we
      characterized activities of HIV-IN with oligonucleotide substrates varying in
      length. Our previous studies indicate that the preferred cation in vitro for 3'
      processing is altered from Mn2+ to Mg2+ by increasing the length of the
      oligonucleotide substrate. This study demonstrates that HIV-IN efficiently
      catalyzes Mg(2+)-dependent 3'-processing while repressing the strand transfer
      reaction. Substrate competition studies indicate that longer substrates
      preferentially bind to the viral DNA binding site of the integrase, whereas the
      shorter substrate has much less specificity. In addition, the shorter substrate
      requires a higher concentration of Mg2+, indicating that there is an alteration
      in the metal binding affinity associated with the varying substrates. Our results
      show that substrate-length-dependent differential activities are due to
      differences in the divalent metal binding and DNA binding affinities associated
      with the different substrates. These results suggest that the structure of the
      viral DNA is an important factor in differentiating the donor and target
      substrates.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7640277
TI  - N-proximal sequence motif in light-harvesting chlorophyll a/b-binding protein is
      essential for the trimerization of light-harvesting chlorophyll a/b complex.
AB  - The major light-harvesting complex (LHCII) of photosystem II can be reconstituted
      in its native, trimeric form starting from its apoprotein light-harvesting
      chlorophyll a/b-binding protein (LHCP), pigments, and thylakoid lipids. In this
      paper we identify segments in the LHCP polypeptide that are essential for the
      formation of stable LHCII trimers by analyzing N- and C-terminal deletion mutants
      of LHCP and mutants carrying point-specific amino acid exchanges. C-terminal
      deletions that do not abolish pigment binding to LHCP do not affect trimerization
      either. By contrast, on the N-terminus of LHCP, where as many as 61 amino acids
      can be deleted without significant effects on pigment binding, only 15 amino
      acids are dispensible for LHCII trimer formation. This indicates that structural
      elements between amino acids 16 and 61 are involved in the stabilization of LHCII
      trimers but not monomers. Closer inspection of this protein domain in a more
      detailed mutation analysis revealed that amino acids W16 and/or Y17 as well as
      R21 are essential for the formation of LHCII trimers. These amino acids are
      conserved in virtually all known sequences of LHCII apoproteins but only in some
      of the minor chlorophyll a/b complexes. Possible functions of the crucial
      residues are discussed.

PMID- 7640279
TI  - Photoelectric characterization of forward electron transfer to iron-sulfur
      centers in photosystem I.
AB  - The photoelectric response of oriented PS I membranes from the cyanobacterium
      Synechocystis 6803 has been investigated in the nanosecond time range. Besides an
      unresolved rapidly rising phase, there is a further positive electrogenic phase
      with a rise time constant of 220 +/- 20 ns. The amplitude of the 220-ns phase is
      66 +/- 10% that of the subnanosecond phase. The fast phase contains two kinetic
      components faster than 100 ps, which have recently been resolved and attributed
      to primary charge separation (P+Ao-formation) and subsequent electron transfer to
      A1, respectively (Hecks, B., Wulf, K., Breton, J., Leibl, W., & Trissl, H.-W.
      (1994) Biochemistry 33, 8619-8624). The 220-ns phase is lost under conditions
      where iron-sulfur centers FA, FB, and Fx are prereduced, and its kinetics match
      the reoxidation kinetics of A1- as verified by absorbance change measurements at
      380 nm. Therefore, this electrogenic phase is attributed to electron transfer to
      the iron-sulfur centers that function as further electron acceptors in the PS I
      reaction center. Gradual removal of FA and FB by urea treatment reveals that the
      amplitude of the 220-ns phase is linearly correlated with the fraction of FA,B
      present. However, complete removal of FA,B does not lead to a complete loss of
      the nanosecond phase but reduces its amplitude by more than a factor of 2 to
      yield an amplitude of 25-30% relative to the initial picosecond rise, with only a
      slight change in kinetics. The residual amplitude is further reduced when a large
      fraction of Fx is removed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7640278
TI  - 13C magic angle spinning NMR characterization of the functionally asymmetric QA
      binding in Rhodobacter sphaeroides R26 photosynthetic reaction centers using site
      specific 13C-labeled ubiquinone-10.
AB  - Photosynthetic reaction centers (RCs) of Rhodobacter sphaeroides R26 were
      reconstituted at the QA site with ubiquinone-10, selectively 13C-enriched on
      positions 1, 2, 3, 4, and 3-Me (IUPAC numbering). RCs dispersed in LDAO detergent
      were studied with 13C CP/MAS NMR spectroscopy at temperatures between 180 and 240
      K, while RCs precipitated by removal of the detergent were investigated at
      ambient temperature and at temperatures down to 180 K. Electrostatic charge
      differences in QA induced by polarization from the protein are less than 0.02
      electronic equivalent for any of the labeled positions. This includes the 4
      carbonyl, which is therefore not significantly polarized by an electrostatic
      binding interaction with the protein. The QA site is slightly heterogeneous on
      the scale of the NMR as the observed line widths of the labels are between 150
      and 300 Hz and inhomogeneous broadening is observed for the signals of positions
      1, 2, and 3 upon cooling. This contrasts with earlier MAS observations for labels
      in the vicinity of the special pair. The chemical shifts are 184, 144, and 137
      ppm for the labels at positions 1, 2, 3, and 12 ppm for the 3-methyl 13C. For the
      4-carbonyl only at sample temperatures below approximately 255 K a CP/MAS
      response can be observed at 183 ppm. The principal components of the chemical
      shift tensors for the ring labels in QA were estimated using difference
      spectroscopy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7640281
TI  - Three-dimensional structure in solution of the calcium channel blocker omega
      conotoxin MVIIA.
AB  - The three-dimensional solution structure of omega-conotoxin MVIIA, a 25-mer
      peptide antagonist of N-type calcium channels, was determined by two-dimensional
      1H NMR spectroscopy with simulated annealing calculations. A total of 13
      converged structures of omega-conotoxin MVIIA were obtained on the basis of 273
      experimental constraints, including 232 distance constraints obtained from
      nuclear Overhauser effect (NOE) connectivities, 22 torsion angle (phi, chi 1)
      constraints, and 19 constraints associated with hydrogen bonds and disulfide
      bonds. The atomic root mean square difference about the averaged coordinate
      positions is 0.47 +/- 0.08 A for the backbone atoms (N, C alpha, C) and 1.27 +/-
      0.14 A for all heavy atoms of the entire peptide. The molecular structure of
      omega-conotoxin MVIIA is composed of a short triple-stranded antiparallel beta
      sheet. The overall beta-sheet topology is +2x, -1, which is the same as that
      reported for omega-conotoxin GVIA, another N-type calcium channel blocker. The
      orientation of beta-stranded structure is similar to each other, suggesting that
      the conserved disulfide bond combination is essential for the molecular folding.
      We have recently determined by using alanine substitution analyses that Tyr 13 is
      essential for the activity of both toxins. On the basis of functional and
      structural analysis, it is shown that both omega-conotoxin MVIIA and GVIA retain
      a similar conformation to locate Tyr 13 in the appropriate position to allow
      binding to N-type calcium channels. These results provide a molecular basis for
      understanding the mechanism of calcium channel modulation through the toxin
      channel interaction and insight into the discrimination of different subtypes of
      calcium channels.

PMID- 7640280
TI  - Structure of CuB in the binuclear heme-copper center of the cytochrome aa3-type
      quinol oxidase from Bacillus subtilis: an ENDOR and EXAFS study.
AB  - We have studied the structure of the CuB site in the binuclear heme-copper center
      of the fully oxidized form of the quinol-oxidizing cytochrome aa3-600 from
      Bacillus subtilis by EXAFS and ENDOR spectroscopy. This enzyme is member of the
      large superfamily of heme-copper respiratory oxidases, which catalyze the
      reduction of dioxygen to water and link it to translocation of protons across the
      bacterial or mitochondrial membrane. The EXAFS of the CuB site strongly suggests
      tetragonal coordination by two or three histidines with one or two O/N donor
      ligands. There are some indications that a Cl- ion might fractionally occupy
      substitution-labile sites, although the majority of enzyme molecules did not
      contain any heavy (second row) scatters, indicative of a Cl- (or S) bridge
      between the heme iron and CuB [cf. Powers, L., et al. (1994) Biochim. Biophys.
      Acta 1183, 504-512]. Proton ENDOR spectroscopy of the CuB site in 1H2O and 2H2O
      media showed evidence of an oxygenous copper ligand with an exchangeable proton.
      14N ENDOR revealed three inequivalent nitrogenous ligands with hyperfine coupling
      constants consistent with histidines. Together, these results strongly suggest
      that the fully oxidized enzyme has a low-symmetry, tetragonal CuB site with three
      histidine nitrogens and one oxygen as ligands, the latter with an exchangeable
      proton(s). The identity and assignment of these ligands are discussed.

PMID- 7640283
TI  - Long amyloid beta-protein secreted from wild-type human neuroblastoma IMR-32
      cells.
AB  - The 39- to 43-amino acid amyloid beta-protein (A beta) is deposited as amyloid in
      Alzheimer's disease. Recent studies have suggested that short A beta (A beta 39
      or A beta 40) and long A beta (A beta 42 or A beta 43) play different roles in
      Alzheimer-type pathology. However, little attempt has been made to investigate
      the cellular mechanisms underlying the generation of short and long A beta
      individually. In the present report, we first measured the amount of short and
      long A beta that are secreted from wild-type human and rodent cells with neuron-
      or glia-like properties using highly sensitive sandwich-ELISAs that discriminate
      long A beta from short A beta. The results showed that long A beta secreted by
      all cells constitutes approximately 10% of the total A beta. To identify the
      molecular species of long A beta, we next isolated the A beta species secreted
      from human neuroblastoma IMR-32 cells by affinity chromatography, gel-filtration
      HPLC, and reverse-phase HPLC. Mass spectrometric analysis demonstrated
      unequivocally that IMR-32 cells produce A beta 1-42 together with A beta 1-37, A
      beta 1-38, A beta 1-39, and most predominantly, A beta 1-40. Finally, to
      investigate the cellular mechanisms that generate A beta 1-42, we studied the
      effects of brefeldin A and monensin on the production of A beta 1-40 and A beta 1
      42 in IMR-32 cells. These reagents reduced the production of both A beta 1-40 and
      A beta 1-42 simultaneously in a concentration-dependent manner.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7640282
TI  - Identification of a plasminogen binding region in streptokinase that is necessary
      for the creation of a functional streptokinase-plasminogen activator complex.
AB  - Streptokinase is a plasminogen activator widely used to treat patients with
      myocardial infarction. However, streptokinase is not a protease, and must first
      bind and interact with plasminogen to form an enzymatic complex. By measuring the
      binding of recombinant streptokinase fragments to plasminogen, we have sought,
      first, to identify a plasminogen binding region in streptokinase and, second, to
      explore the relation between binding (via this region) and the generation of a
      functional streptokinase--plasminogen activator complex. Recombinant
      streptokinase bound in a saturable and specific manner to human Glu-plasminogen
      with a dissociation constant of 4.2 x 10(-10) M. Recombinant streptokinase
      fragments spanning amino acids 1-127 and 1-253 could not be shown to bind to Glu
      plasminogen, whereas fragments spanning amino acids 1-352, 120-352, and 244-414
      bound tightly to plasminogen and each fragment completely inhibited the binding
      of full-length streptokinase to plasminogen. Although these latter streptokinase
      fragments formed a complex with plasminogen, enzymatic assays indicated that none
      of them was capable of generating an active site. When the streptokinase region
      shared by these three fragments, spanning residues 244-352, was expressed, it
      also bound plasminogen and competitively inhibited the formation of a functional
      plasminogen activator complex by full-length streptokinase. Taken together, these
      data indicate that streptokinase binds to plasminogen with high affinity, that a
      primary binding region for plasminogen is located within amino acids 244-352, and
      that binding via this region is necessary for the generation of a functional
      plasminogen activator complex.

PMID- 7640285
TI  - Rate-limiting mechanisms of exchange reactions in the cardiac sarcolemma Na(+)
      Ca2+ exchanger.
AB  - The effects of temperature, pH, voltage and K+ were tested on Na(+)-Ca2+ and
      Ca(2+)-Ca2+ exchanges with a goal to elucidate the rate-limiting mechanisms. The
      initial rates (t = 1 s) of Nai- and Cai-dependent 45Ca uptakes were measured in
      the sarcolemma vesicles. At pH 7.4 the Ca(2+)-Ca2+ exchange shows a bell-shaped
      temperature curve with a maximum at 27-29 degrees C. This effect is not caused by
      irreversible inactivation of the exchanger. The increase of pH from pH 6.0 to 7.4
      in the K(+)-free medium decelerates the Ca(2+)-Ca2+ exchange 1.5-2.0-fold, while
      the addition of K+ accelerates the Ca(2+)-Ca2+ exchange 2.0-3.0-fold. Therefore,
      the accelerating effect of K+ opposes the decelerating effect of deprotonation.
      Temperatures increase (6-45 degrees C) in the K(+)-free medium (pH 7.4) elevates
      the Na(+)-Ca2+/Ca(2+)-Ca2+ exchange ratio from 0.8 to 5.0. With varying
      temperatures (6-37 degrees C) and pH 5.0-9.7, K+ has no considerable effect on
      Na(+)-Ca2+ exchange but accelerates the Ca(2+)-Ca2+ exchange 2-3-fold. At 6-45
      degrees C and fixed pH 7.4, the inside-positive potential (delta psi > or = +200
      mV) accelerates the Na(+)-Ca2+ exchange 1.7-2.0-fold, suggesting that the same
      rate-limiting reaction controls the Na(+)-Ca2+ exchange at various temperatures.
      It is concluded that (a) At pH > 6.5 (6-45 degrees C and 0-100 mM K+) the voltage
      sensitive Na+ efflux limits the Na(+)-Ca2+ exchange, while the Ca2+ efflux limits
      the Ca(2+)-Ca2+ exchange.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7640284
TI  - Pulmonary surfactant protein SP-A with phospholipids in spread monolayers at the
      air-water interface.
AB  - Spread monolayers of pulmonary surfactant protein SP-A, alone or mixed with
      phospholipid(s), were formed at the air-water interface. Binary monolayers of SP
      A plus dipalmitoylphosphatidylcholine (DPPC) showed positive deviations from
      ideal behavior of the mean areas in the films consistent with partial miscibility
      and interaction between the protein and lipid. During compression of SP-A/DPPC
      films which contained > or = 5 wt % SP-A, properties were displayed which were
      consistent with the protein being partially squeezed out at surface pressures of
      about 30 mN/m. Some protein appeared to remain in the monolayers even when they
      were compressed to high surface pressures of about 65-70 mN/m, and it was
      possibly included in the collapse phase(s) that was (were) formed at 72 mN/m.
      During dynamic cyclic compression-expansion of SP-A/DPPC monolayers initially
      formed at low surface pressures, SP-A enhanced the respreading of the films
      compressed beyond collapse compared to the respreading after collapse of films
      containing DPPC alone. Spread monolayers of SP-A plus either
      dipalmitoylphosphatidylglycerol (DPPG) or a mixture of DPPC plus DPPG (7:3,
      mol/mol) displayed additivity of the mean areas in the films, consistent with
      complete immiscibility (or ideal miscibility, an unlikely effect) between the
      protein and lipid components. Electrostatic repulsion between SP-A and DPPG, both
      negatively charged at physiological pH, possibly governed the behavior of these
      lipid-protein films. Calcium ions in the subphase did not alter the properties of
      SP-A/DPPC films, whereas they improved the ability of SP-A to mix with DPPG and
      DPPC/DPPG. Binding of calcium to the negatively charged DPPG and SP-A may account
      for association of the protein with DPPG and DPPC/DPPG in the monolayers in the
      presence of the divalent ions.

PMID- 7640287
TI  - Catalysis of a protein folding reaction: mechanistic implications of the 2.0 A
      structure of the subtilisin-prodomain complex.
AB  - Biosynthesis of subtilisin is dependent on a 77 amino acid, N-terminal prodomain,
      which is autocatalytically processed to create the mature form of the enzyme
      [Ikemura, H., Takagi, H., & Inouye, M. (1987) J. Biol. Chem. 262, 7859-7864]. In
      order to better understand the role of the prodomain in subtilisin folding, we
      have determined the structure of the processed complex between the prodomain and
      subtilisin Sbt-70, a mutant engineered for facilitated folding. The prodomain is
      largely unstructured by itself but folds into a compact structure with a four
      stranded antiparallel beta-sheet and two three-turn alpha-helices when complexed
      with subtilisin. The Ka of the complex is 2 x 10(8) M-1 at 25 degrees C. The
      prodomain binds on subtilisin's two parallel surface alpha-helices and supplies
      caps to the N-termini of the two helices. The C-terminal strand of the prodomain
      binds in the subtilisin substrate binding cleft. While Sbt-70 is capable of
      independent folding, the prodomain accelerates the process by a factor of > 10(7)
      M-1 of prodomain in 30 mM Tris-HCl, pH 7.5, at 25 degrees C. X-ray structures of
      the mutant subtilisin folded in vitro either with or without the prodomain are
      compared and show that the identical folded state is achieved in either case. A
      model of the folding reaction of Sbt-70 and the prodomain is described as the
      following equilibria: P + Su<-->Pf--SI<-->Pf--Sf, where Su and P are Sbt-70 and
      prodomain, respectively, which are largely unstructured at the start of the
      reaction, Pf--SI is a collision complex of a partially folded Sbt-70 and folded
      prodomain, and Pf--Sf is the complex of folded Sbt-70 and prodomain.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7640286
TI  - Complex interactions between SP1 bound to multiple distal regulatory sites and
      HNF-4 bound to the proximal promoter lead to transcriptional activation of liver
      specific human APOCIII gene.
AB  - Footprinting analysis of the human apoCIII promoter identified a set of four
      proximal (A-D) and six distal (E-J) regulatory elements between nucleotides -792
      and -25 [Ogami, K., et al. (1990) J. Biol. Chem. 265, 9808-9815]. The distal
      regulatory elements of the apoCIII gene increase by 10-fold the strength of the
      homologous as well as of heterologous proximal promoters. Required for such
      transcriptional enhancement is the presence of an intact hormone response element
      (HRE) on the proximal promoter which binds a variety of nuclear hormone
      receptors. To understand the mechanism of this transcriptional activation, we
      identified the nature and the importance of the factors which bind to the
      upstream regulatory elements of the apoCIII promoter by DNA binding, competition,
      supershift, and transient transfection assays. These analyses showed that the
      upstream apoCIII promoter contains multiple binding sites for the ubiquitous
      transcription factor SP1, which recognizes the regulatory elements F, H, and I.
      The regulatory element G represents a specialized HRE which is recognized by the
      orphan receptors ARP-1 and EAR-3 but not by HNF-4. A single activity designated
      CIII J1 binds to the regulatory element J. The same or a similar activity binds
      as a minor component to the regulatory elements F and I where SP1 is the
      predominant binding activity. Finally, a minor activity designated CIII 15 binds
      to the regulatory element I.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7640288
TI  - Molecular biology of nicotinamide nucleotide transhydrogenase--a unique proton
      pump.

PMID- 7640289
TI  - Raman detection of a peroxy intermediate in the hydroquinone-oxidizing cytochrome
      aa3 of Bacillus subtilis.
AB  - When the mixed valence, carbon monoxide-bound form of the hydroquinone-oxidizing
      cytochrome aa3-600 of Bacillus subtilis is illuminated in the presence of O2, it
      forms a species that corresponds to 'Compound C', first described for the
      mitochondrial cytochrome c oxidase by Chance, Saronio and Leigh (J. Biol. Chem.
      250 (1975) 9226-9237). Resonance Raman spectra of the this species show a mode at
      366 cm-1 that shifts to 342 cm-1 when the experiment is repeated with 18O2. The
      appearance of this mode is insensitive to deuteration exchange within the limits
      of resolution. High- (1200-1700 cm-1) and low-frequency (200-500 cm-1) data,
      allow us to assign the 366 cm-1 mode to the Fe(3+)-O stretching vibration of a
      peroxide adduct where the iron is either low or intermediate spin. This is to our
      knowledge the first time an 18O2-sensitive iron-oxygen stretching mode has been
      reported for 'Compound C', providing strong support for the notion that this
      species is a peroxide adduct. The observed 366 cm-1 v(Fe(3+)-O(-)-O-) frequency
      is 8 cm-1 higher than that previously found for a transient peroxy intermediate
      in the reaction between the fully reduced mitochondrial enzyme and O2. Our
      observation indicates that, while similar, the metastable peroxyheme a3 species
      reported here differs in the fine details of geometry, protonation state, and/or
      hydrogen bond status.

PMID- 7640290
TI  - The coding sequence of the bovine ferrochelatase gene.
AB  - The amino acid code and surrounding regions in the bovine ferrochelatase gene
      were amplified by a combination of reverse transcriptase PCR and vectorette PCR
      and sequenced. The bovine code was 86% homologous to the human ferrochelatase
      code but was altered at a position corresponding to the presumed human initiator
      codon.

PMID- 7640293
TI  - Liposomes and ISCOMS as vaccine formulations.

PMID- 7640292
TI  - Force-velocity relations of rat cardiac myosin isozymes sliding on algal cell
      actin cables in vitro.
AB  - The difference in kinetic properties between two myosin isozymes (V1 and V3) in
      rat ventricular myocardium was studied by determining the steady-state force
      velocity (P-V) relations in the ATP-dependent movement of V1 and V3-coated
      polystyrene beads on actin cables of giant algal cells mounted on a centrifuge
      microscope. The maximum unloaded velocity of bead movement was larger for V1 than
      for V3. The velocity of bead movement decreased with increasing external load
      applied by the centrifuge microscope, and eventually reached zero when the load
      was equal to the maximum isometric force (P0) generated by the myosin heads. The
      maximum isometric force P0 was less than 10 pN, and did not differ significantly
      between V1 and V3. The P-V curves consisted of a hyperbolic part in the low force
      range and a non-hyperbolic part in the high force range. The critical force above
      which the curve deviated from the hyperbola was much smaller for V1 than for V3.
      An analysis using a model with an extremely small number of myosin heads involved
      in the bead movement suggested a marked difference in kinetic properties between
      V1 and V3.

PMID- 7640291
TI  - Initial spectroscopic characterization of the ciliate photoreceptor stentorin.
AB  - Stentorin serves as the primary photosensor in the single cell ciliate, Stentor
      coeruleus, for its photophobic and phototactic response to light of visible
      wavelengths. We separated two subunits, stentorin-2A and -2B, from the previous
      stentorin complex ('stentorin-2') of greater than half a million molecular mass
      isolated from the photoreceptor organelle (pigment granule). Stentorin-2B bears
      the chromophore covalently linked to an approx. 50 kDa apoprotein, as determined
      by SDS-urea-PAGE. Partial amino acid sequences were obtained from this 50 kDa
      subunit. Its visible and CD spectra were found to be similar to those of
      stentorin-2. The steady-state and time-resolved fluorescence spectra of stentorin
      2B, in H2O and D2O buffers, were also similar to those of stentorin-2. This
      suggests that the 50 kDa subunit retains the spectral integrity and primary
      photoreactivity of the stentorin-complex. The picosecond time-resolved
      fluorescence study revealed that the short picosecond emission component (tau F
      approximately equal to 8-10 ps) was the predominant emitting species in stentorin
      2B and -2, followed by longer decaying species. No deuterium solvent effect was
      seen in this fast-decaying species. The possible mechanism for the primary
      photoreaction appears to involve electron transfer coupled with proton transfer.

PMID- 7640294
TI  - The mitochondrial permeability transition.

PMID- 7640295
TI  - Mannose 6-phosphate receptors in sorting and transport of lysosomal enzymes.
AB  - Mannose 6-phosphate receptors have been intensively studied with regard to their
      genomic organization, protein structure, ligand binding properties, intracellular
      trafficking and sorting functions. That their main function is sorting of newly
      synthesized lysosomal enzymes is commonly accepted, but much more remains to be
      learned about their precise recycling pathways and the mechanisms which regulate
      their vesicular transport. Additional functions have been reported, e.g., export
      of newly synthesized lysosomal enzymes from the cell by MPR 46 or a--probably
      indirect--participation in growth factor-mediated signal transduction by MPR 300.
      To understand the physiological relevance of these observations will be a
      challenge for future research.

PMID- 7640296
TI  - Chloride-dependent amino acid transport in the small intestine: occurrence and
      significance.
AB  - The unidirectional influx of amino acids, D-glucose and ions across the brush
      border membrane of the small intestine of different species has been measured in
      vitro with emphasis on characterization of topographic and species differences
      and on chloride dependence. The regional differences in transport along the small
      intestine are outlined and shown to be caused by variation in transport capacity,
      while the apparent affinity constants are unchanged. Rabbit small intestine is
      unique by exhibiting maximal rates of transport in the distal ileum and a very
      steep decline in the oral direction from where tissues are normally harvested for
      preparation of brush-border membrane vesicles. Transport in the guinea pig and
      rat is much more constant throughout the small intestine. Since the capacity of
      nutrient carriers is regulated by their substrates it is possible that bacterial
      breakdown of peptides and proteins in rabbit distal ileum increases the
      concentration of amino acids leading to an upregulation of the carriers. Chloride
      dependence is a characteristics of the carrier rather than the transported amino
      acid, and is used to improve the classification of amino acid carriers in rabbit
      small intestine. In this species the imino acid carrier, the beta-amino acid
      carrier, and the beta-alanine carrier, which should be renamed the B0,+ carrier,
      are chloride-dependent. The steady-state mucosal uptake of classical substrates
      for these carriers in biopsies from the human duodenum is also chloride
      dependent. The carrier of beta-amino acids emerges as ubiquitous and chloride
      dependent, and evidence of cotransport with both sodium and chloride is reviewed.
      A sodium:chloride:2-methyl-aminoisobutyric acid coupling stoichiometry of approx.
      2:1:1 is suggested by ion activation studies. Direct measurements of coupled ion
      fluxes in rabbit distal ileum confirm that sodium, chloride and 2-methyl
      aminoisobutyric acid are cotransported on the imino acid carrier with an
      identical influx stoichiometry. Control experiments and reference to the
      literature on the electrophysiology of the small intestine exclude alterations of
      the membrane potential as a feasible explanation of the chloride dependence.
      Thus, it is concluded that chloride is cotransported with both sodium and 2
      methyl-aminoisobutyric acid across the brush-border membrane of rabbit distal
      ileum.

PMID- 7640297
TI  - Hepatobiliary secretion of organic compounds; molecular mechanisms of membrane
      transport.

PMID- 7640298
TI  - Interaction of detergents with lipid vesicles.

PMID- 7640299
TI  - Forces and factors that contribute to the structural stability of membrane
      proteins.
AB  - While a considerable amount of literature deals with the structural energetics of
      water-soluble proteins, relatively little is known about the forces that
      determine the stability of membrane proteins. Similarly, only a few membrane
      protein structures are known at atomic resolution, although new structures have
      recently been described. In this article, we review the current knowledge about
      the structural features of membrane proteins. We then proceed to summarize the
      existing literature regarding the thermal stability of bacteriorhodopsin,
      cytochrome-c oxidase, the band 3 protein, Photosystem II and porins. We conclude
      that a fundamental difference between soluble and membrane proteins is the high
      thermal stability of intrabilayer secondary structure elements in membrane
      proteins. This property manifests itself as incomplete unfolding, and is
      reflected in the observed low enthalpies of denaturation of most membrane
      proteins. By contrast, the extramembranous parts of membrane proteins may behave
      much like soluble proteins. A brief general account of thermodynamics factors
      that contribute to the stability of water soluble and membrane proteins is
      presented.

PMID- 7640300
TI  - The duck gene for alpha B-crystallin shows evolutionary conservation of discrete
      promoter elements but lacks heat and osmotic shock response.
AB  - The gene for alpha Beta-crystallin from a bird (the domestic duck, Anas
      platyrhynchos) has been cloned and sequenced to allow comparison with its
      mammalian homologues. The duck gene has the same general structure as those of
      humans and rodents although, unlike those of mammals, the duck gene has two
      polyadenylation signals at the 3' end. The most interesting comparisons are in
      the 5'flanking promoter regions. In contrast to the broad conservation of
      promoter sequence among mammals, only two significant blocks and a few smaller
      elements have been conserved during evolution in the more distantly related avian
      gene. Block 1 (-350/-308) corresponds to alpha BE-2, a functional element defined
      in the mouse gene. Further downstream, block 2 (-98/-65) shows 27/33 identity
      among all three species but does not correspond to any previously defined
      element. Other regions are less well-conserved. In particular, putative heat
      shock response elements of the mammalian alpha B-crystallin genes are absent from
      the duck gene. In contrast to the heat and osmotic stress-inducibility of mouse
      alpha B-crystallin in NIH 3T3 cells, duck alpha B-crystallin showed no
      inducibility in duck cells in culture. Thus, although high expression in lens is
      common to alpha B-crystallin genes in birds and mammals, other modes of
      expression appear to be taxon-specific.

PMID- 7640302
TI  - Regulation of c-jun mRNA expression by hydroxyurea in human K562 cells during
      erythroid differentiation.
AB  - Hydroxyurea (HU) is an antitumor agent which also induces hemoglobinization
      during erythroid differentiation. In addition, HU stimulates the synthesis of
      fetal hemoglobin in sickle cell anemia patients. To further understand its
      mechanism of action, we investigated the effects of HU on regulation of c-jun
      expression prior to the onset of erythroid differentiation of K562 cells. HU
      induced a dose-dependent stimulation of c-jun synthesis. The levels of c-jun mRNA
      was elevated 4 to 7.5-fold by HU within 2 h. This was followed by a gradual
      decline to the basal level by 24 h. Both nuclear run-on and actinomycin D pulse
      experiments strongly indicate that HU regulates c-jun mRNA expression by
      increasing the rate of synthesis as well as stabilizing the c-jun mRNA. In
      addition, the level of jun protein was elevated by 2 to 5-fold within 4 h in HU
      treated cells. Furthermore, concentrations of HU below 250 microM slightly
      increased the 5X AP-1/CAT activity. These results strongly suggest that HU
      induces both transcriptional and post-transcription regulation of c-jun during
      erythroid differentiation.

PMID- 7640304
TI  - An aphidicolin-resistant mutant of Chinese hamster ovary cell with altered DNA
      polymerase and 3' exonuclease activities.
AB  - A comparison was made of partially purified DNA polymerases alpha, delta, epsilon
      and from normal Chinese hamster ovary cells and mutant cells (JK3-1-2A) resistant
      to aphidicolin, araA, and araC. In vitro the pol alpha from the mutant cells (1)
      was resistant to aphidicolin and araCTP but was sensitive to araATP, (2) showed a
      1.6 to 2.6-fold reduced specific activity, and (3) was more sensitive to
      carbonyldiphosphonate, DMSO and SJK 287-38 anti-pol alpha antibody inhibition,
      but was less sensitive to alkylphenyl nucleotide analogs BuPdGTP and BuAdATP. On
      the other hand, pol delta and pol epsilon of the mutant cells did not show
      increased aphidicolin-resistance but differed from the wild type enzymes with
      regard to their 3' exonuclease activity. The 3' exonuclease/DNA polymerase
      activity ratio was increased 6-fold for pol delta and 3.3-fold for pol epsilon
      for enzymes from the mutant cells in comparison to wild type values. It is
      suggested that these altered properties of the DNA polymerases of the alpha
      family are responsible for in vivo aphidicolin resistance of the mutant cells.
      The higher 3' exonuclease activity may explain the observed antimutator phenotype
      of this cell line. In view of the proficient 3' exonuclease activities of the DNA
      pol delta and epsilon, the present aphr mutant is unique among all mammalian DNA
      polymerase mutants.

PMID- 7640303
TI  - Transcriptional regulation of the ezrin gene during rat intestinal development
      and epithelial differentiation.
AB  - Polarized intestinal epithelial cells are characterized by the presence of a
      brush border at their apical surface. The brush border cytoskeleton is assembled
      during cell differentiation and is composed of parallel actin bundles, held
      together by specific actin-binding proteins. Using specific cDNA probes we have
      studied the expression of the mRNAs encoding ezrin and moesin, two members of a
      class of proteins that connect the microvillar cytoskeleton to the plasma
      membrane, during the process of enterocyte maturation that occurs both in the
      embryonic and in the adult small intestine, along the crypt-villus axis. The
      steady state levels of ezrin mRNA were found to increase in the fetal gut
      epithelium between day 15 and day 20 of gestation and during the first week after
      birth, in parallel with the morphogenetic process that leads to cell polarization
      and brush border assembly. On the contrary, moesin mRNA is expressed at very low
      levels in the mature small intestine, with a sudden drop in transcription
      occurring at birth. In the continuously renewing epithelium of adult animals,
      ezrin mRNA levels are higher in the differentiated villus cells of the distal
      portions of the gastrointestinal tract and very low in undifferentiated crypt
      cells. These data demonstrate that the expression of the ezrin gene is regulated
      at the level of mRNA abundance during development and differentiation of the
      intestinal epithelium.

PMID- 7640305
TI  - Transcriptional control of the osteocalcin gene by 1,25-dihydroxyvitamin D-2 and
      its 24-epimer in rat osteosarcoma cells.
AB  - The effects of two vitamin D analogs, 1,25-dihydroxyvitamin D-2 and 24-epi-1,25
      dihydroxyvitamin D-2, were examined on osteocalcin gene expression in the rat
      osteosarcoma cell line ROS 17/28. Our results indicate that these analogs are
      more transcriptionally active than 1,25-dihydroxyvitamin D-3, particularly the 24
      epimer. Assessment of reporter gene chloramphenicol acetyltransferase (CAT)
      activity, using the vitamin D responsive element (VDRE) derived from the human
      osteocalcin gene promoter. revealed that both analogs stimulated CAT activity 5-
      to 10-fold. 1,25-Dihydroxyvitamin D-2 was slightly more active than 1,25
      dihydroxyvitamin D-3, while the 24-epimer was twice as effective. 1,25
      Dihydroxyvitamin D-3 also stimulated osteocalcin mRNA accumulation by 2-fold over
      vehicle-treated cells, 1,25-dihydroxyvitamin D-2 by 2.5-fold, and 24-epi-1,25
      dihydroxyvitamin D-2 by 4-fold. Electrophoretic mobility shift assays using the
      osteocalcin vitamin D responsive element revealed no increase in DNA binding with
      either analog when compared to 1,25-(OH)2D3. Examination of CAT activity using
      the rat 24-hydroxylase VDRE indicated no significant difference in transcription
      with these compounds, suggesting that the vitamin D-2 analogs preferentially
      activate osteocalcin gene expression.

PMID- 7640306
TI  - Conserved amino acid residues in the primary structure of ribosomal protein S20
      from selected gram-negative bacteria.
AB  - Partial DNA sequences encoding ribosomal protein S20 have been determined for a
      number of Gram-negative bacteria including three species of Aeromonas, Klebsiella
      pneumoniae, Proteus mirabilis, and Salmonella typhimurium and compared to the
      known sequence from Escherichia coli. The derived amino acid sequence is well
      conserved, particularly in the C-terminal one-third of S20. In contrast, there is
      much less conservation of the nucleotide sequence or potential secondary
      structure in the corresponding mRNA.

PMID- 7640301
TI  - Transcription factors as targets for oxidative signalling during lymphocyte
      activation.
AB  - We previously have demonstrated a requirement for oxidative events during cell
      cycle entry in T lymphocytes and have hypothesised that reactive oxygen species
      may act as intracellular signalling agents during lymphocyte activation. In the
      current study, cysteamine, an aminothiol compound with antioxidant activity, has
      been used to further investigate the role of oxidative signalling during
      lymphocyte activation. Treatment of normal human peripheral blood lymphocytes
      with cysteamine in vitro was found to inhibit proliferation in a dose-dependent
      manner, with essentially complete inhibition occurring at a dose of 400 microM.
      This inhibitory effect was limited to the first 2 h after mitogenic activation,
      localizing the time-frame of action of cysteamine to within the commitment
      period. It therefore was of interest to establish which, if any, commitment
      events were affected by oxidative signalling during cell cycle entry. Taking the
      IL-2 gene as a candidate, we examined the effect of cysteamine treatment on early
      gene expression during lymphocyte activation, and on the activity of
      transcription factors AP-1, NF-kappa B, NF-AT and Oct1, whose functions are
      required for expression of the IL-2 mRNA. Cysteamine treatment inhibited both
      expression of the IL-2 mRNA and secretion of IL-2 into the culture medium. The
      inhibitory effect of cysteamine may be mediated at least in part by an effect on
      transcription factor function, as the DNA binding activities of AP-1 and NF-kappa
      B extracted from mitogen-stimulated cells were significantly inhibited by
      cysteamine treatment. Interestingly, Oct1 and NF-AT DNA binding activity were not
      affected by cysteamine treatment, suggesting that oxidative signalling processes
      operate in a selective manner. The identification of regulatory proteins, such as
      transcription factors, as molecular targets for oxidative signalling provides
      further evidence to implicate oxidative signalling as being intimately involved
      in the G0 to G1 phase transition in T lymphocytes.

PMID- 7640307
TI  - Molecular cloning and nucleotide sequence of the genomic DNA for 1,2-alpha-D
      mannosidase gene, msdC from Penicillium citrinum.
AB  - A gene encoding 1,2-alpha-D-mannosidase (EC 3.2.1.113) was cloned from
      Penicillium citrinum genomic DNA using the polymerase chain reaction (PCR). The
      coding region of the gene, msdC, occupied 1737 bp and was separated into four
      exons by three introns. The predicted protein consisted of 511 amino acid
      residues with M(r) 56,569. Penicillium enzyme had a hydrophobic signal peptide at
      the N-terminal region as did mammalian membrane-bound alpha-mannosidases, but in
      this case a proteolytic cleavage occurred at Lys-35-Ser-36 to remove the signal
      sequence during cell growth. Parts of amino acid sequences were similar to those
      of mammalian Golgi alpha-mannosidase IA and IB, but the sequence around the
      aspartic acid residue which interacted with 1-deoxymannojirimycin (Yoshida et al.
      (1994) Biochem. J. 303, 97-103) was unique in Penicillium enzyme.

PMID- 7640308
TI  - Deer antler tissue contains two types of bone morphogenetic protein 4 mRNA
      transcripts.
AB  - Previously we isolated a bone morphogenetic protein 4 (BMP-4) cDNA from human
      prostate cancer cells and found that the 5' noncoding exon 1 of this BMP-4 cDNA
      was different from that of human bone cell BMP-4 cDNA. Recently we identified two
      alternate exon 1s, 1A and 1B, for BMP-4 gene by reverse transcription-polymerase
      chain reaction (RT-PCR) assays from fetal rat calvarial osteoblasts. In order to
      further examine alternate exon 1 usage in the BMP-4 gene, we screened deer antler
      tissue cDNA library. We isolated two types of cDNA clones encoding BMP-4 from
      this deer antler cDNA library. Sequencing of these clones have revealed a single
      open reading frame encoding a 408 amino acid protein. Comparison of 5' noncoding
      exon 1 portion of these cDNA sequences with those of human bone and prostate BMP
      4 cDNA sequences and mouse BMP-4 genomic DNA sequence demonstrated that deer
      antler tissue expresses both exon 1A and 1B containing BMP-4 mRNA transcripts.
      This suggests that BMP-4 gene may contain alternate promoters or alternate
      splicing sites in deer antler tissue.

PMID- 7640309
TI  - The human high mobility group (HMG)-box transcription factor TCF-1: novel
      isoforms due to alternative splicing and usage of a new exon IXA.
AB  - The C-terminal peptide sequences of the human lymphocyte-specific high mobility
      group (HMG)-box transcription factor TCF-1 are determined by alternative splice
      mechanisms affecting the exons VIII to X. Here we report, in addition to four
      splice forms described previously (TCF-1A, B, C, D), the identification of three
      novel transcripts designated TCF-1E, F, G. Cloning and sequencing of the novel
      cDNAs revealed (i) joining of the exons VIII and IX to an internal exon X splice
      acceptor site resulting in a new open reading frame (ORF) of 99 amino acids
      derived from exon X sequences, (ii) the identification of an additional
      functional splice acceptor site within exon X, and (iii) a new 81-nucleotide
      insertion between exon VIII and exon X sequences in a novel transcript form.
      Genomic cloning and sequence analysis of this transcribed segment of 81 basepairs
      revealed that it was bordered by canonical splice consensus sites and located in
      a distance of some 400 bp from both the exons IX and X. It was therefore termed
      exon IXA. Novel ORFs were generated as a consequence of these alternative splice
      mechanisms resulting in TCF-1 gene products with significantly different C
      terminal peptide sequences, which are prone to selective protein-protein
      interactions or transactivating functions.

PMID- 7640311
TI  - Nucleotide sequence of the bacterial streptothricin resistance gene sat3.
AB  - The nucleotide sequence of the sat3 gene which encodes resistance of enteric
      bacteria to the antibiotic streptothricin is reported. A protein with a molecular
      mass of about 23 kDa is expressed from this gene. The sat3 gene is not obviously
      related to any one of the streptothricin resistance determinants identified so
      far among Gram-negative or Gram-positive bacteria.

PMID- 7640312
TI  - Amino acid oxidation and urea production rates in fetal life.
AB  - Amino acid oxidation and urea production rates are quite different at various
      stages of development from fetal to adult life. Such information may become
      increasingly useful in the evaluation of the nutritional state in newborn infants
      and particularly in very-low-birth-weight infants. A brief commentary on some of
      the current clinical and basic physiological literature as it relates to amino
      acid oxidation and urea production is presented. The commentary emphasizes that
      the literature supports the concept of a higher urea production rate expressed
      per kilogram body weight in late fetal life as compared with postnatal life. It
      also discusses some differences for the phases of fetal life, the period of
      parturition, and the immediate neonatal period.

PMID- 7640310
TI  - Mouse cytochrome P-450 linked ferredoxin: its cDNA cloning and inducibility by
      dibutyryladenosine 3',5'-cyclic monophosphate and forskolin.
AB  - Two full-length cDNAs (F1-1 and F41-1) complementary to mouse kidney mRNA coding
      for cytochrome P-450 (P450) linked ferredoxin were isolated and completely
      sequenced. The coding sequences between F1-1 and F41-1 were identical. However,
      the 3' untranslated regions of F1-1 and F41-1 were 228 and 27 bases long due to
      the presence of alternative polyadenylation sites, respectively. The deduced
      amino acid sequence of mouse cytochrome P-450 linked ferredoxin showed 92.5,
      75.0, 71.2 and 71.0% identities with those of rat, human, pig and bovine
      cytochrome P-450 linked ferredoxin, respectively. The cytochrome P-450 linked
      ferredoxin mRNA was detected in adrenal, kidney and ovary among the organs
      examined. The treatment of Y-1 cells with dibutyryladenosine 3',5'-cyclic
      monophosphate or forskolin induced the transcript of cytochrome P-450 linked
      ferredoxin mRNA.

PMID- 7640313
TI  - Maternal-fetal folate status and neural tube defects: a case control study.
AB  - The object of this study was to explore the role of folate in the pathophysiology
      of neural tube defects (NTD). Maternal and fetal serum and red blood cell folate
      were assayed in 14 cases of NTDs and compared with 14 controls with other
      malformations and matched for gestational age (range 18-36 weeks). In mothers of
      NTD fetuses, serum folate (5.2 ng/ml), red blood cell folate (294 ng/ml) and the
      folate methylation rate (65%) were significantly lower than in controls (6.6 and
      399 ng/ml, respectively, and 77%). However, the fetal folate status was similar
      in cases and controls. In the NTD group, folate metabolism was altered in the
      mothers but not in the fetuses. Therefore, a normal folate placental transfer can
      be assumed in this group. In addition, it could be speculated that decreased
      maternal folate methylation might be involved in the pathogenesis of NTDs.

PMID- 7640314
TI  - Obstetric risk factors affecting incidence of low birth weight in live-born
      infants.
AB  - This study was conducted to determine the incidence of low birth weight (LBW) in
      the indigenous population of Al Ain and to identify some risk factors associated
      with it. The population studied included all consecutive deliveries, occurring in
      the 3 hospitals in Al Ain City, where almost all deliveries take place, during a
      1-year period. When a LBW infant (< 2,500 g) was born, gestational age assessment
      was made and a questionnaire completed during an interview with the mother. For
      control, the first baby who weighed more than 2,500 g at birth, following the
      birth of a LBW was recruited. It was found that a total of 3,485 live births
      occurred of which 293 were classified as LBW, giving an LBW incidence of 8.4%. Of
      these, 73 (24.9%) were small for gestational age (< 10th percentile for
      gestational age). Overall, the mothers of LBW infants were found to be
      statistically significantly younger in age. The mothers of LBW infants also had a
      significantly higher number of previous LBW deliveries, twin deliveries and a
      larger number of premature rupture of membranes. The factors that were not
      significantly different in the 2 groups were diabetes during pregnancy, chronic
      hypertension, preeclampsia/eclampsia, occurrence of significant infection during
      pregnancy, 1st and 2nd trimester bleeding, and antepartum hemorrhage. This is the
      first comprehensive study on the incidence of LBW infants in the United Arab
      Emirates. The main obstetric factors responsible for this were found to be age,
      number of previous LBW babies, premature rupture of membranes and multiple
      births.

PMID- 7640315
TI  - Closure of patent ductus arteriosus decreases pulmonary myeloperoxidase in
      premature infants with respiratory distress syndrome.
AB  - The aim of the study was to determine whether in premature infants with
      respiratory distress syndrome (RDS), an interrelationship existed between patent
      ductus arteriosus (PDA) and pulmonary neutrophil content. Thirteen premature
      infants with PDA (gestational age 26.9 +/- 2.4 weeks, birth weight 903 +/- 300 g)
      were pair-matched with infants without PDA (gestations age 27.1 +/- 2.5 weeks,
      birth weight 1,041 +/- 430 g) with regard to gestational age, birth weight and
      severity of RDS. The myeloperoxidase (MPO) contents of tracheal aspirates were
      analyzed before (age 2.8 +/- 1.7 days, MPO I) and after closure of PDA with
      indomethacin (5.5 +/- 1.9 days, MPO II), and at corresponding time points in
      controls (2.6 +/- 1.6 and 4.8 +/- 1.8 days). In PDA patients closure of PDA
      decreased MPO from 14.7 (range 2.1-27.4) to 4.6 (1.2-8.0) micrograms/mg protein
      (p = 0.0008), whereas in controls it remained unchanged: 5.4 (2.9-7.8) and 5.3
      (2.9-7.8; p = 0.58). A significant difference existed in the change in MPO
      contents between the infants with PDA and the controls. In premature infants with
      RDS, closure of PDA decreases the neutrophil content of the lungs. The effect may
      be caused by closure of PDA as such, or by indomethacin. The high pulmonary
      neutrophil content in PDA may exacerbate inflammatory processes and contribute to
      the development of chronic pulmonary disease.

PMID- 7640316
TI  - Early minimal feedings promote growth in critically ill premature infants.
AB  - Critically ill premature infants requiring mechanical ventilation and an
      umbilical artery catheter usually do not receive enteral feedings during the
      acute phase of their illness. We studied the safety and benefit of early minimal
      enteral feedings during this time in a prospective, controlled, and randomized
      study. Twenty-nine infants were randomly assigned to receive only standard
      intravenous fluid and nutrition (nothing per OS, NPO group; n = 13), or in
      addition to receive small-volume hypocaloric continuous feedings (1 ml/kg/h),
      beginning at 24 h of age (early-feeding group; n = 16). Standard enteral feedings
      were begun in both groups at the resolution of the acute phase of the illness and
      advanced by protocol. The two groups were of comparable birth weight, gestational
      age, and Apgar scores. There were no significant differences in the episodes of
      feeding intolerance. Two infants in the NPO group developed clinical signs of
      necrotizing enterocolitis. Serum diamine oxidase and somatomedin C were measured
      weekly until 30-60 days of age and were not different between the two groups. The
      early-feeding group required fewer days to reach 120 ml/kg/day enteral intake
      (early-feeding group 10 +/- 3 days, NPO group 13 +/- 4 days; p < 0.05). On day 30
      of life the early-feeding group was 223 +/- 125 g above birth weight, while the
      NPO group was 95 +/- 161 g above birth weight (p < 0.05). The average intake
      (kcal/kg/day) from day 6 to day 30 was not different between the two groups. We
      conclude that early minimal feedings in critically ill very-low-birth-weight
      infants requiring mechanical ventilation are well tolerated and result in reduced
      time to reach 120 ml/kg/day of enteral feeding and in a greater weight gain by
      day 30 of life.

PMID- 7640317
TI  - End-tidal carbon monoxide in newborn infants: observations during the 1st week of
      life.
AB  - Serial end-tidal carbon monoxide corrected for ambient CO (ETCOc) levels were
      measured in an ethnically diverse population of 87 normal newborn infants during
      the first 5 days of life. The results demonstrate a progressive reduction in
      ETCOc from 1.6 +/- 0.4 to 0.8 +/- 0.2 ppm. These levels were unrelated to
      ethnicity, but were inversely related to serum bilirubin levels. We conclude that
      ETCOc is not a useful indicator for predicting the course of transitional
      hyperbilirubinemia in the normal newborn infant.

PMID- 7640318
TI  - Effect of hypoinsulinemia on growth in the fetal rabbit.
AB  - Insulin is an important regulatory hormone in the control of fetal growth. In a
      fetal rabbit model, a non-ruminant species, the effects of insulin deprivation on
      glucose, growth and protein metabolism were studied. The fetuses of 10 pregnant
      New Zealand white rabbits in one uterine horn received a subcutaneous injection
      on day 25 of gestation (term = 30 days) of 0.1 mg streptozotocin (STZ)/gm fetal
      weight. The fetuses in the opposite horn received a sham injection of buffer. The
      dams were then killed on day 29. The fetal insulin concentration was depressed by
      38%, and the serum glucose concentration was elevated by 28% in animals given STZ
      when compared to control animals. Fetal weights, carcass weights and skeletal
      growth, as measured by crown-rump length and tibial length of STZ-treated
      fetuses, were significantly reduced by 7-13%. However, organ weights were not
      significantly different, except for the kidneys which were 17% lighter. Protein
      and mineral contents of the carcasses were also reduced compared to the control
      fetuses. Thus, insulin deprivation in fetal rabbits results in significant growth
      impairment in a pattern similar to that of human asymmetric intrauterine growth
      retardation.

PMID- 7640319
TI  - Lack of production and growth-modulating effects of 1a,25-dihydroxyvitamin D3 in
      cultured fetal rat hepatocytes.
AB  - 1a,25-Dihydroxyvitamin D3 [1,25(OH)2D3], the hormonal form of vitamin D3, has
      been shown to play a role in the regulation of growth of the regenerating adult
      rat liver following partial hepatectomy. In addition, a recent study implicated
      the neonatal liver as a possible extrarenal site of 1,25(OH)2D3 synthesis.
      Therefore, in our present study we used rapidly growing fetal hepatocytes in
      culture as a model cell line for regenerating hepatocytes and tested the
      hypothesis that fetal hepatocytes locally produce 1,25(OH)2D3 which in turn
      regulates their growth. Hepatocytes isolated from 19-day rat fetuses were grown
      in culture for 24 h in minimal essential medium without added serum or mitogens.
      To identify 1,25(OH)2D3 production, we incubated fetal hepatocytes in culture
      with 3H-25-hydroxyvitamin D3 (3H-25-OH D3) for 2, 6 and 24 h. High-pressure
      liquid chromatographic analysis of the lipid extract of the medium and cells
      revealed no evidence of conversion of 3H-25-OH D3 into 3H-1,25(OH)2D3.
      Additionally, to investigate the effect of 1,25(OH)2D3 on DNA synthesis in fetal
      liver, we measured 3H-thymidine incorporation by the cultured fetal hepatocytes
      following 24 h of exposure to various concentrations of 1,25(OH)2D3. The results
      of DNA synthesis revealed no effect of 1,25(OH)2D3 on fetal hepatocyte growth. As
      alterations in growth regulation by 1,25(OH)2D3 in other cells are thought to be
      mediated by intracellular vitamin D receptors (VDR), the expression of the VDR
      message in the fetal and maternal tissues of a pregnant rat was studied. RNA was
      first isolated from fetal liver, fetal kidney, maternal liver and maternal
      kidney, and the corresponding cDNA was then generated by reverse
      transcription.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7640320
TI  - Acute entry of bilirubin into rat brain regions.
AB  - In kernicterus bilirubin appears at higher concentrations in the basal ganglia,
      the cerebellum, and the medulla. The mechanism for this distribution is unknown,
      but might involve differences in bilirubin entry among brain regions. We infused
      [3H]bilirubin (30 mg/kg over 5 min) intravenously into young Sprague-Dawley rats
      (n = 21, weight 144 +/- 10 g, mean +/- SD). Blood was sampled from the tail, and
      groups of rats were killed at 15, 30, 45, 60, and 75 min by intravenous
      pentobarbital. After in situ flushing of the brain vasculature, the brain was
      dissected into seven regions, each of which was weighed, dissolved in Soluene
      350, and subsequently scintillation counted. Blood samples were analyzed for
      bilirubin (including specific activity), albumin, and blood gases. Brain
      bilirubin concentrations in each of the regions were calculated by comparing the
      radioactivity in that region with the specific activity of bilirubin. Using a
      curve-fitting program (EXPOFIT), the concentrations of bilirubin in each brain
      region at 5 min (i.e. the end of bilirubin infusion) could be estimated, and were
      as follows (nmol/g +/- SD): cortex 6.4 +/- 4.4; hippocampus 6.2 +/- 3.3; striatum
      6.3 +/- 4.5; midbrain 7.3 +/- 4.4; hypothalamus 6.3 +/- 4.6; cerebellum 6.7 +/-
      4.1, and medulla 7.0 +/- 4.0. There were no significant differences in the
      bilirubin concentrations between brain regions (F6,140 0.205). The mechanism for
      preferential localization of bilirubin to the basal ganglia probably does not
      involve the acute entry of bilirubin into brain.

PMID- 7640321
TI  - Retinal and choroidal blood flow response to hyperoxemia after severe hypoxemia
      in the newborn piglet.
AB  - To investigate the effect of hyperoxemia on the ocular circulation after a severe
      hypoxemic insult (8% O2 until base excess reached -20 mmol/l), we randomly
      reoxygenated newborn piglets with 100% (study group, n = 8) or 21% O2 (control
      group, n = 10). Retinal (RBF) and choroidal blood flow (ChBF) were measured with
      radioactive microspheres. The hypoxemic insult did not change RBF, while ChBF
      significantly decreased. However, a marked reduction in both retinal (RDO2) and
      choroidal oxygen delivery (ChDO2) was observed, probably resulting in hypoxia
      both in the inner and outer retina. At 5 and 20 min of reoxygenation a similar
      hyperemic response in the retina was seen in both groups. RDO2 also increased
      significantly and no significant differences between the 2 groups could be
      demonstrated. We found no indication of retinal vasoconstriction during
      hyperoxemia. We speculate that the vasodilating effect of the preceding hypoxemia
      overrules the vasoconstrictive effect of the retinal vessels normally found
      during hyperoxemia.

PMID- 7640322
TI  - Does endothelin-1 mediate the hypoxemia-induced renal dysfunction in newborn
      rabbits?
AB  - In the newborn rabbit, acute normocapnic hypoxemia increases the renal vascular
      resistance, leading to renal hypoperfusion and decreased glomerular filtration
      rate. Endothelin is a potent vasoconstrictor peptide, produced by vascular
      endothelial cells, which could play a role as a mediator of the hypoxemia-induced
      renal dysfunction. To test this hypothesis, experiments were performed in 24
      anesthetized and mechanically ventilated newborn rabbits. Renal blood flow and
      glomerular filtration rate were determined by the clearance of p-aminohippuric
      acid and inulin, respectively. Each animal acted as its own control. In 8 newborn
      rabbits (group 1), a bolus injection of 5 nmol.kg-1 of endothelin caused a marked
      increase in mean blood pressure and renal vascular resistance leading to a
      significant fall in glomerular filtration rate (-12 +/- 4%) and renal blood flow
      (-16 +/- 3%). A second group of animals (n = 8) confirmed the neutralizing
      activity of the endothelin-1 antiserum in vivo. In spite of pretreatment with
      endothelin-1 antiserum, hypoxemia induced an increase in renal vascular
      resistance (+40 +/- 18%; p < 0.05) associated with a significant fall in
      glomerular filtration rate (-18 +/- 7%) and renal blood flow (-29 +/- 6%) in 8
      newborn rabbits (group 3). The present results suggest that endothelin-1 does not
      mediate the hypoxemia-induced renal changes.

PMID- 7640323
TI  - Negative symptoms of schizophrenia: where do we go from here?

PMID- 7640324
TI  - Cholecystokinin messenger RNA deficit in frontal and temporal cerebral cortex in
      schizophrenia.
AB  - No consistent markers of pathology have been established yet in schizophrenia,
      although abnormalities in frontal and temporal structures are indicated from
      positron emission tomography (PET) studies. We have used in situ hybridization to
      investigate functional changes focusing on the quantitation of cholecystokinin
      (CCK) mRNA, whose product has been shown to be depleted in schizophrenia. CCK
      mRNA and G(o) alpha-subunit mRNA were measured in eight schizophrenic and eight
      control subjects matched for age and postmortem delay. The study revealed a
      marked decrease in CCK mRNA of 83% in frontal cortex (BA10) and 63% in superior
      temporal cortex (BA22) in schizophrenia with no change in G(o) alpha-subunit mRNA
      in either region. This study was extended to a further series of eight patients
      to determine the reproducibility of this effect and to quantitate laminar changes
      in CCK mRNA. Quantitation of CCK mRNA in inner cortical layers (layer V/VI) was
      carried out in frontal and temporal cortex in comparison with G(o) alpha-subunit
      mRNA, which is also concentrated in this region; this study showed a similar
      selective decrease in CCK mRNA in frontal and temporal cortex of 47% and 51%,
      respectively. A confirmatory decrease in CCK mRNA was also obtained by slot blot
      analysis of CCK mRNA in tissue extracts of frontal cortex by reference to levels
      of beta-tubulin mRNA, CCK mRNA:beta-tubulin mRNA was significantly decreased
      (67%) in schizophrenic tissue compared to control tissue. There was no
      significant correlation of CCK mRNA loss with neuroleptic treatment or duration
      of illness.

PMID- 7640325
TI  - Improved event-related potential signs of selective attention after the
      administration of the cholecystokinin analog ceruletide in healthy persons.
AB  - Cholecystokinin (CCK) is co-localized with dopamine (DA) in neurons of the
      mesolimbic-frontocortical dopamine (DA) system, considered essential for the
      pathology of psychotic behavior and associated attention deficits. The present
      experiments in 13 healthy men aimed at examining the effects of the CCK analog
      ceruletide on attention as reflected by event-related brain potentials (ERPs).
      Subjects were tested according to a double-blind cross-over design on three
      occasions, following intravenous infusion of placebo, 0.5 microgram ceruletide,
      and 2.5 micrograms ceruletide. ERPs were recorded during the subject's
      performance on an auditory selective attention task including the concurrent
      presentation of frequent standard tones and infrequent deviant tones which the
      subject had to listen to, or to ignore. The processing negativity (PN) over
      frontocentral cortical areas, reflecting selective attention, was higher after
      ceruletide than placebo, this increase being most pronounced after the 2.5
      micrograms dose (placebo -1.29 +/- 0.38 microV versus ceruletide -3.02 +/- 0.65
      microV, p < .05). ERP signs of a general increase in cortical arousal after
      ceruletide did not reach significance. Likewise, mismatch negativity, an
      indicator of preattentive processing of stimulus deviance, was not significantly
      affected by the peptide. The results indicate that ceruletide affects human brain
      function primarily by improving selective attention.

PMID- 7640326
TI  - Seizure threshold in electroconvulsive therapy: I. Initial seizure threshold.
AB  - We measured initial seizure threshold by means of a structured stimulus dosage
      titration procedure in a clinical sample of 111 depressed patients undergoing
      brief-pulse, constant-current electroconvulsive therapy (ECT). Initial seizure
      threshold was approximately 60 millicoumbs (mc) (10 Joules) on average, but
      varied widely (6-fold) across patients. Initial seizure threshold was predicted
      by four variables: electrode placement (higher with bilateral), gender (higher in
      men), age (higher with increasing age), and dynamic impedance (inverse
      relationship). Use of neuroleptic medication was associated with a lower seizure
      threshold. EEG seizure duration was inversely related to initial seizure
      threshold, but no other relations with seizure duration were found. These
      findings may have important clinical implications for stimulus dosing strategies
      in ECT.

PMID- 7640328
TI  - Differential impairments of selective attention due to frequency and duration of
      cannabis use.
AB  - The evidence for long-term cognitive impairments associated with chronic use of
      cannabis has been inconclusive. We report the results of a brain event-related
      potential (ERP) study of selective attention in long-term cannabis users in the
      unintoxicated state. Two ERP measures known to reflect distinct components of
      attention were found to be affected differentially by duration and frequency of
      cannabis use. The ability to focus attention and filter out irrelevant
      information, measured by frontal processing negativity to irrelevant stimuli, was
      impaired progressively with the number of years of use but was unrelated to
      frequency of use. The speed of information processing, measured by the latency of
      parietal P300, was delayed significantly with increasing frequency of use but was
      unaffected by duration of use. The results suggest that a chronic buildup of
      cannabinoids produces both short- and long-term cognitive impairments.

PMID- 7640327
TI  - Alterations in heart rate and pupillary response in persons with organic solvent
      exposure.
AB  - Cardiac and pupillary reactivity were examined in 25 persons with a history of
      exposure to organic solvents and 19 nonexposed controls during performance of a
      counting and a choice reaction task. The solvent-exposed group demonstrated an
      atypical pattern of responding across tasks. While control subjects showed a
      decline in heart rate across the two conditions (e.g., habituation), exposed
      persons had an increase in heart rate. Initial pupil diameter was similar for
      both groups, but only the control subjects exhibited habituation across the two
      tasks. In the exposed group, higher heart rate was not associated with higher
      levels of self-reported anxiety. Anticipatory cardiac deceleration preceding
      unpredictable events was significantly less in the exposed group, but there were
      no significant group differences on poststimulus acceleration. The results
      suggest that persons with solvent exposure have a deficiency in the allocation of
      attention (reduced anticipatory deceleration and decreased pupillary dilation).
      It is further suggested that difficulty in the allocation of attention produces
      an increase in tonic sympathetic levels when confronted with a cognitively
      challenging task. In this experiment, in which the choice reaction task was
      purposely presented last, and was apparently more challenging for exposed
      persons, a failure to exhibit autonomic habituation over the course of the
      session characterized the solvent-exposed group.

PMID- 7640329
TI  - Hormonal responses to the administration of m-chlorophenylpiperazine in patients
      with seasonal affective disorder and controls.
AB  - We report on the plasma cortisol and prolactin responses to the serotonergic
      agonist m-CPP (0.1 mg/kg) in 10 patients with winter seasonal affective disorder
      (SAD) and 10 controls during the winter, in both untreated and bright light
      treated conditions; and on 8 other SAD patients and 8 other controls during the
      summer. Following m-CPP infusion, untreated patients had exaggerated prolactin (p
      < .05) and cortisol (p < .05) responses compared to controls. Light treatment
      significantly reduced responses of both hormones to m-CPP (prolactin: p < .01;
      cortisol: p < .01). When untreated winter subjects and summer subjects were
      compared, cortisol, but not prolactin responses to m-CPP were found to be higher
      in patients than in controls during the winter, and lower in patients than in
      controls during the summer (diagnosis by season: p < .05). These results are
      consistent with those of our previous report on the behavioral responses to m-CPP
      in the same patients and suggest an abnormality in serotonergic function in
      untreated SAD patients in winter, which is normalized following treatment with
      light therapy and naturally during the summer.

PMID- 7640330
TI  - Verbal learning and memory in relatives of schizophrenics: preliminary findings.

PMID- 7640331
TI  - Delayed peak latency of the mismatch negativity in schizophrenics and alcoholics.

PMID- 7640332
TI  - Histologic probe penetration in healthy and inflamed peri-implant tissues.
AB  - Periodontal probing is commonly used for assessing both the status of gingival
      health and the connective tissue attachment level around teeth. The role of
      probing around endosseous implants still remains unclear. The purpose of this
      study was to determine the histological level of probe penetration in healthy and
      inflamed mucosal tissues around implants. Five beagle dogs were used and a total
      of 30 one-stage, Titanium Plasma Spary (TPS)-coated implants of the ITI type were
      placed in the mandibles. After the healing period with meticulous oral hygiene,
      the dogs were divided into 3 groups: 1) clinical healthy mucosal tissues; 2)
      experimental mucositis (3 dogs); and 3) experimental ligature-induced peri
      implantitis (2 dogs). Four months after implant placement, respectively 6 months
      in the third group, 60 probes were placed with a standardized force of 0.2 N and
      fixed at the mesial and distal aspects of the implants. Probing depth, clinical
      attachment level (CAL), Plaque Index (PlI) and Gingival Index (GI) were assessed
      throughout the study. Tissue sections were obtained for histometrical analysis.
      In the healthy group, the mean PII was 0.47, the GI 0.06 and the clinical probing
      depth (CPD) 2.12 mm. In the mucositis group the PlI was 1.61, the GI 1.61 and the
      CPD 1.87 mm. In the peri-implantitis group the PlI was 1.96, the GI 2.05 and the
      CPD 3.73 mm. The histologic results show that the probes were able to identify
      the connective tissue adhesion level in the healthy group with a mean error of 
      0.05 mm (mean histologic probing depth (HPD): 1.75 mm) and, in the mucositis
      group, with -0.02 mm (mean HPD: 1.62 mm). Probe penetration increased with the
      degree of inflammation and in the peri-implantitis group the probe exceeded the
      connective tissue level by a mean 0.52 mm (mean HPD: 3.8 mm). Therefore, probing
      around implants represents a good technique for assessing the status of peri
      implant mucosal health or disease.

PMID- 7640333
TI  - A histomorphometric evaluation of bone-to-implant contact on machine-prepared and
      roughened titanium dental implants. A pilot study in the dog.
AB  - This investigation was performed to assess the bone-to-implant surface contact at
      fixtures of titanium that either had a standard machine prepared or a TiO2
      blasted surface. Five beagle dogs were used in the experiment. Extractions of the
      premolars were performed in the maxilla. After 4 months of healing, 5 standard
      machine-prepared fixtures and 5 prepared according to the TioBlast technique were
      inserted. Two months later another 5 "standard" and 5 TioBlast-prepared implants
      were inserted. Four months after the first fixture installation, the animals were
      killed and ground sections prepared from each implant site. Of the 20 implants
      installed, 19 were successfully incorporated. The mean bone-to-implant surface
      for "standard" fixtures was about 40% both at the 2 and 4 months observation
      interval. The corresponding figures for the TioBlast-prepared fixtures were
      similar during the first 2 months of observation, while subsequently the TioBlast
      prepared fixture surface seemed to stimulate to a more close bone-to-implant
      contact (65%) than the "standard" one.

PMID- 7640334
TI  - Overdentures supported by two IMZ implants in the lower jaw. A retrospective
      study of peri-implant tissues.
AB  - Between 1987 and 1990, 57 edentulous patients were treated with overdentures
      supported by 2 endosseous IMZ implants connected by a bar in the lower jaw. The
      condition of the peri-implant tissue was evaluated for a loading period ranging
      from 12 to 57 months (mean 30 months and median 24 months). The evaluation
      parameters included Plaque Index, Bleeding Index, Gingiva Index, pocket depth,
      dysesthesia of chin or lip, peri-implant bone loss and loss of implants. During
      the healing phase prior to the construction of an overdenture, 3 implants were
      lost. After a healing period of 6 months, these implants were successfully
      replaced. During the follow-up period, a Plaque Index < or = 1 was observed in 45
      patients and an abundance of plaque and calculus was observed in 1 patient. Heavy
      or profuse bleeding and severe gingival inflammation was observed in 3 patients.
      The mean pocket depth was 3.6 +/- 1.7 mm. None of the patients experienced lip or
      chin dysesthesia. Marginal bone loss was observed around 30 (26%) implants. From
      this study it is concluded that, once proper osseointegration is obtained, 2 IMZ
      implants connected with a bar in the lower jaw supply a proper base for the
      support of an overdenture; the condition of the peri-implant tissues is steady
      and independent of the follow-up time.

PMID- 7640335
TI  - Titanium implant insertion into dog alveolar ridges augmented by allogenic
      material.
AB  - The purpose of this investigation was to evaluate whether titanium endosseous
      implants would osseointegrate in dog alveolar ridges augmented by allogenic
      material. In 8 dogs en bloc resection, including 2 pre-molars, was performed
      bilaterally in the maxilla and the mandible. After a healing period of 6 weeks
      allogenic, demineralized and lyophilized dentin or bone was implanted
      subperiosteally. Titanium implants were installed 5.5 months later in some of the
      regions. Light and fluorescence microscopic evaluation revealed fibrous
      encapsulation of the implanted allogenic material, no osteoinduction and only
      minimal osteoconduction, few multinuclear giant cells and a sparse inflammatory
      reaction. The titanium implants healed mainly by fibrous encapsulation.

PMID- 7640336
TI  - Mucosal topography around implants in edentulous upper jaws. Photogrammetric
      three-dimensional measurements of the effect of replacement of a removable
      prosthesis with a fixed prosthesis.
AB  - A photogrammetric technique was tested to measure the topography of the mucosa
      around implants, placed in edentulous upper jaws. Photographs were taken of casts
      from 6 patients, who all had used a removable overdenture for one year. Another
      series of photographs was taken on new casts after the use of a fixed prosthesis
      for a second year. The 6 pairs of photographs were measured and compared in an
      analytical stereo plotter for surface contour and implant positions. The results
      from the measurements indicated a trend of general recession of the mucosa after
      one year with fixed prosthesis, both on the buccal as well as on the palatal
      side. The mean volume of recession was 222.4 mm3, corresponding to an average of
      0.4 mm3/mm2 of mucosa. More recession was generally observed on the palatal side,
      but obvious variations between the patients were present. In conclusion, the
      photogrammetric technique was considered to be well suited for analysing tissue
      contours in various dental situations.

PMID- 7640337
TI  - A comparison of the diagnostic advantages of panoramic radiography and computed
      tomography scanning for placement of root form dental implants.
AB  - This study evaluated the advantages of computed tomography (CT) in comparison to
      routine panoramic radiography for dental implant treatment planning. An in vitro
      validation study was performed to assess the accuracy of CT and panoramic
      radiography film images for measurement of anatomic structures and distances
      between anatomic structures. After correcting by a standard 25% magnification on
      the panoramic images, a significant difference in measurements was found between
      the CT and panoramic radiography images. Ten subjects requiring implants in
      compromised ridges were treatment planned with either CT and panoramic
      radiographs or panoramic radiographs alone. The ideal implant length was
      determined at surgery with direct digital radiography. The dentists were
      significantly more confident using CT and panoramic images than panoramic
      radiographs alone. Implant length treatment planned with panoramic radiography
      alone underestimated length significantly compared with the implant length
      determined to be ideal during surgery, whereas treatment planning with CT and
      panoramic radiography demonstrated no significant difference. The data indicate
      the CT may be of value in treatment planning for dental implants, especially when
      gaining maximum length is of critical importance.

PMID- 7640338
TI  - Microbial penetration along the implant components of the Branemark system. An in
      vitro study.
AB  - This study examined in vitro the existence of microbial leakage along the
      components of the Branemark implant system. Thirty-two implant/abutment
      assemblies were installed in a liquid blood medium previously inoculated with
      oral micro-organisms. To examine the leakage at the implant-abutment interface,
      16 assemblies were partially immersed. The remaining 16 were completely immersed
      to observe the leakage at both the implant-abutment and abutment-prosthesis
      interface. After 7 days of anaerobic incubation, the micro-organisms in the
      internal part of the implants were collected and incubated on blood agar plates
      in anaerobic conditions. Micro-organisms were found in the completely immersed
      assemblies and at lower numbers in the partially immersed implants, indicating
      that bacterial leakage at both levels seems to exist. Several penetrating
      bacteria have been associated with peri-implantitis. The clinical importance of
      this bacterial leakage is not yet well understood. Although the longevity of the
      Branemark implants is well documented, this bacterial leakage might play a role
      in peri-implantitis, both in the etiology as well as in the treatment.

PMID- 7640339
TI  - Formation of jawbone tuberosities by guided tissue regeneration. An experimental
      study in the rat.
AB  - The aim of this study was to explore the possibility of creating bone
      tuberosities on the mandibular ramus in rats, using a rigid, occlusive, Teflon
      capsule. The experiment was carried out in 30 rats. The mandibular ramus was
      exposed bilaterally. On the test side, the periosteum was left covering the
      lateral surface of the ramus. On the contralateral side (control), the periosteum
      was elevated from the lateral surface together with the flap. A hemispherical,
      Teflon capsule was then placed to face the periosteum or the bone surface with
      its open part before closure of the wound. The healing periods comprised 7-120
      days. Histological analysis demonstrated increasing bone fill in the test
      specimens from 7 to 60 days, and a limited further increase was observed from 60
      to 120 days. In the control specimens, limited bone fill was seen within the
      first month after surgery, but substantial amounts of new bone were produced from
      30-120 days. At 120 days, the mean amount of bone obtained in the test specimens
      was 56% (range 39%-71%) of the total space created by the capsules, and it was
      52% (range 32%-85%) in the controls. The amount of newly formed bone was
      equivalent to a 5-6 times increase of the original width of the mandibular ramus.
      These findings indicate that a secluded space created by an occlusive barrier
      adjacent to existing bone or periosteum may be filled out with bone tissue. This
      may have a great clinical impact in cranial and maxillofacial surgery.

PMID- 7640340
TI  - Experimentally induced peri-implant mucositis. A clinical study in humans.
AB  - The purpose of this study was to compare the clinical and microbiological
      (microscopic) parameters during the development of experimental gingivitis and
      experimental peri-implant mucositis. Twenty partially edentulous patients were
      treated for moderate to advanced periodontal disease. Following active
      periodontal therapy consisting of motivation, instruction in oral hygiene
      practices, scaling and root planing and periodontal surgery where indicated, IMZ
      oral implants were incorporated in posterior edentulous areas. After 3 months of
      healing, the prosthetic abutments were connected, and the patients were closely
      supervised for another 2 months of healing. At this time, baseline data were
      obtained. Re-examinations were scheduled at 3 and 6 months. Following this, the
      patients were asked to refrain from oral hygiene practices for 3 weeks. At all
      examinations including the end of the period of no oral hygiene, the following
      clinical parameters were obtained: Plaque Index, Gingival Index and Sulcus
      Bleeding Index, all modified by Mombelli et al. (1987), probing pocket depths and
      recession in mm. Furthermore, submucosal/subgingival plaque samples were obtained
      and analyzed using phase contrast microscopy. At the end of the 3-week period of
      plaque accumulation, optimal oral hygiene was reinstituted. There were no
      statistically significant differences between the mean values of all parameters
      at implant compared to tooth sites at any observation periods. The period of no
      oral hygiene demonstrated a similar cause-effect relationship between the
      accumulation of bacterial plaque and the development of peri-implant mucositis as
      established for the gingival units by the experimental gingivitis model.

PMID- 7640341
TI  - The effect of smoking on early implant failure.
AB  - This retrospective study describes the effect of smoking on initial fixture
      failure before functional loading with fixed prosthetic restorations. Of 208
      installed Branemark fixtures in the mandible, only 1 failed (0.5%), and no
      detrimental effect of smoking on fixture survival could be detected. In the
      maxilla, 10/244 fixtures failed (4%); 7/78 fixtures failed in smokers and 3/166
      in nonsmokers. The failure rate before loading was 9% in smokers versus 1% in
      nonsmokers and was statistically significant, despite the fact that bone quality
      in both groups was comparable. Failed fixtures occurred in 31% of the smokers,
      despite often excellent bone quality, long fixture length or good initial
      stability. Only 4% of the nonsmokers had failures, in most cases related to poor
      bone quality. It is concluded that smoking is a significant although not the only
      important factor in the failure of implants prior to functional loading.
      Prospective studies are needed to assess the risk of implant failure in
      conjunction with smoking. In the mean time, patients should be informed of the
      adverse effect of smoking.

PMID- 7640342
TI  - Cloning, sequencing and expression of the ovine interleukin 6 gene.
AB  - Gene amplification by reverse transcriptase PCR with heterologous primers has
      been used to obtain a cDNA clone encoding the structural sequences of ovine
      interleukin 6 from alveolar macrophages. This cDNA encodes a protein of M(r) =
      23,429, which is 53% homologous in amino acid sequence to human IL = 6. The clone
      hybridizes to an RNA of size 1260 nt in alveolar macrophages, expression of which
      is potentiated by LPS. The ovine IL-6 structural gene has been cloned into the
      yeast expression vector pOGS40, and used to produce a recombinant protein. This
      protein is capable of causing increased immunoglobulin production in pokeweed
      mitogen stimulated ovine peripheral blood mononuclear cells at concentrations of
      10-100 ng/ml, but it only causes very limited replication of B9 cells, a murine
      IL-6 dependent cell line. This is in contrast to recombinant human IL-6, which is
      capable of stimulating B9 cell proliferation, but not immunoglobulin production
      by ovine PBMC.

PMID- 7640343
TI  - The rat interleukin 4 receptor: coevolution of ligand and receptor.
AB  - A rat interleukin 4 receptor (IL-4R) cDNA was cloned by polymerase chain reaction
      (PCR) using RNA of Con A activated T cells and primers deduced from mouse and
      human IL-4R sequences. Sequence analysis revealed an open reading frame for a
      putative membrane protein of 800 amino acids in length. It comprises an overall
      identity of 52 and 78% to its human and mouse homologues, respectively. The
      extracellular part of the rat IL-4R contains a number of residues including
      cysteines and a WSXWS motif typical for the cytokine receptor superfamily.
      Analysis of amino acid exchanges between rat and mouse IL-4 receptors deciphered
      for replacement (R) or silent (S) mutations suggested different types of
      selective pressure acting on the extracellular and intracellular domains. A high
      R/S value that indicates selective pressure for amino acid exchanges was found
      for the extracellular domain and a low R/S value for the intracellular part of
      the IL-4R. Since we previously found a similar high R/S value in the rat IL-4
      gene encoding the ligand for the IL-4R, the high amino acid exchange rate can
      best be explained by coevolution between IL-4 and the ligand binding domain of
      the IL-4R to improve or retain affinity.

PMID- 7640344
TI  - Regulation of metallothionein gene expression by TNF-alpha and IFN-beta in human
      fibroblasts.
AB  - We have compared the regulation of the human metallothionein (MT)-IIA gene by the
      cytokines tumour necrosis factor-alpha (TNF) and interferon beta (IFN-beta) in
      human fibroblasts. Both TNF and IFN-beta induced MT-II mRNA rapidly, but
      stimulation by TNF was more sustained. The effects of TNF and IFN-beta were
      further distinguished by the action of the protein synthesis inhibitor
      cycloheximide, which reduced MT-II mRNA stimulation by TNF but enhanced IFN-beta
      induced MT-II mRNA. These results suggested that TNF and IFN-beta activate MT-II
      gene expression by partially distinct mechanisms. Consistent with this notion,
      combined treatment with both cytokines resulted in more than an additive level of
      MT-II mRNA induction. TNF and IFN-beta also acted cooperatively in inducing MT-II
      mRNA in HeLa cells. A reporter construct containing positions -765/+80 of the MT
      II promoter linked to the CAT reporter gene failed to respond to either TNF or
      IFN-beta in HeLa cells, despite the presence of a putative IFN-stimulated
      response element (ISRE) and an activator protein-1 (AP-1) binding site,
      suggesting that these elements are insufficient for the activation of the MT-II
      gene by these cytokines. Thus induction of MT-II expression differs from the
      genes whose activation by TNF can be induced via the AP-1 element alone, as well
      as those genes whose activation by IFN is mediated solely through the ISRE site.

PMID- 7640345
TI  - Chimeric anti-TNF-alpha monoclonal antibody cA2 binds recombinant transmembrane
      TNF-alpha and activates immune effector functions.
AB  - Results of clinical trials have indicated that cA2, a neutralizing mouse/human
      IgG1 chimeric anti-human TNF-alpha monoclonal antibody, may have therapeutic
      benefit for rheumatoid arthritis patients. Arthritic joints contain, in addition
      to elevated levels of soluble TNF-alpha, high numbers of CD4+ T cells and
      macrophages, cells known to express transmembrane TNF-alpha upon activation. For
      that reason, we sought to determine if cA2 binds to transmembrane TNF-alpha and
      what effects such binding may have on TNF-alpha-expressing cells. A cell line
      expressing a cell-surface, mutant form of transmembrane TNF-alpha was prepared
      for these studies. Analysis of these TNF+ cells by flow cytometry, direct
      binding, and competitive binding assays showed that cA2 binds to the
      transmembrane form of TNF-alpha with high avidity. Binding of the IgG1 isotype of
      cA2, but not an IgG4 version of cA2, resulted in efficient killing of the TNF+
      cells by both antibody-dependent cellular toxicity and complement-dependent
      cytotoxicity effector mechanisms. These findings indicate that, in addition to
      blocking soluble TNF-alpha activity, cA2 can bind to transmembrane TNF-alpha in
      vitro and suggest that cA2 binding may lead to lysis of TNF-alpha-expressing
      cells in vivo.

PMID- 7640346
TI  - Influence of cytokines on the density of beta 2-adrenergic receptors on
      peripheral blood mononuclear cells in vitro.
AB  - Previous investigations have demonstrated a decrease of the number of beta 2
      adrenergic receptors (beta 2R) on peripheral blood mononuclear cells (PBMC) in
      patients with rheumatic diseases that correlated with the systemic inflammatory
      activity. However, the main factor(s) modulating the beta 2R on lymphocytes in
      inflammatory diseases are still unidentified. The present study aimed at
      evaluating the influence of interleukin 1 beta (IL-1 beta) and interleukin 2 (IL
      2) on the number and on the dissociation constant (KD) of beta 2R on PBMC in
      vitro. PBMC from healthy volunteers were incubated with different concentrations
      of IL-1 beta (10-100 U/ml) or IL-2 (10-50 U/ml) for 1,6,12,24 and 72 hours (h),
      respectively. Cultures with medium alone served as controls. beta 2R were
      determined using a radioligand binding assay with 125Iodo-cyanopindolol. The
      results showed a significant spontaneous decline of beta 2R after 72 h (mean +/-
      SEM = 2674 +/- 392 binding sites/cell (bs/c) vs. 1131 +/- 149 bs/c P < 0.02). IL
      2 at a concentration of 50 U/ml diminished this spontaneous reduction of beta 2R
      numbers significantly (control: 1439 +/- 139 bs/c vs. IL-2: 1724 +/- 107 bs/c, P
      < 0.05). However, beta 2R densities did not hold baseline levels and were still
      significantly lower as compared to preculture values. Incubation with 100 U/ml IL
      1 beta for 6 h induced a significant increase of beta 2R densities (control: 1760
      +/- 214 bs/c vs. IL-1: 2233 +/- 424 bs/c, P < 0.05).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7640347
TI  - Interleukin 6 production by lipopolysaccharide-stimulated human fibroblasts is
      potently inhibited by naphthoquinone (vitamin K) compounds.
AB  - Naphthoquinone vitamins (vitamins K) are widely recognized for their role in the
      gamma-carboxylation of specific glutamyl residues in coagulation, anti
      coagulation and extra-hepatic proteins. Recently, however, there have been
      reports that these compounds can exert actions other than those normally
      associated with protein gamma-carboxylation. These observations suggest that
      naphthoquinones may have effects on the production of inflammatory mediators
      including cytokines. Fibroblasts are now recognized as a rich source of cytokines
      and we have examined the effect of various naphthoquinones on the production of
      interleukin 6 (IL-6) by lipopolysaccharide-stimulated human gingival fibroblasts.
      Compounds examined in this study include: phylloquinone (K1), menaquinone-4 (K2),
      menadione (K3), 2,3-dimethoxy-1,4-naphthoquinone (DMK) and a synthetic product of
      vitamin K catabolism, 2-methyl, 3-(2'methyl)-hexanoic acid-1,4-naphthoquinone
      (KCAT). All of these compounds are capable of inhibiting IL-6 production with a
      rank order of potency: KCAT > K3 > DMK > K2 > K1. The most potent compound, KCAT,
      inhibited IL-6 production with an IC50 of 3 x 10(-7)M. The mechanism of action of
      these naphthoquinones on fibroblast IL-6 production is unknown. Given that K3 and
      KCAT are inactive in the gamma-carboxylation reaction, we suggest that this
      activity is not essential for the inhibition of IL-6 production and that activity
      may be related to the redox capacity of these naphthoquinones.

PMID- 7640348
TI  - GM-CSF rapidly primes mice for enhanced cytokine production in response to LPS
      and TNF.
AB  - Subcutaneous administration of Granulocyte-macrophage-colony stimulating factor
      (GM-CSF) to mice enhanced LPS-induced cytokine production in the circulation
      (TNF, IL-6) and peritoneal cavity (IL-1 beta, IL-6). This effect was induced
      rapidly (within 1 h) and persisted for 4 h. Mice made leukopenic with
      cyclophosphamide retained the ability to respond to GM-CSF. In addition, TNF
      induced IL-6 production was also enhanced. These results demonstrate that GM-CSF
      has a pronounced priming effect on cytokine producing cells in vivo and raises
      the possibility that this cytokine may contribute to the pathogenesis of septic
      shock.

PMID- 7640349
TI  - Interleukin 4 impairs rat pancreatic islet function in vitro by an action
      different to that of interleukin 1.
AB  - Cytokines, in particular interleukin 1 beta (IL-1 beta), have been implicated in
      pancreatic beta-cell destruction in insulin-dependent diabetes mellitus. In the
      rat prolonged exposure in vitro of islets of IL-1 beta leads to nitric oxide
      formation, impaired glucose metabolism and inhibition of insulin secretion.
      Interleukin 4 (IL-4) has been shown to be able to modulate nitric oxide formation
      in other cell systems. In the present study we have investigated the effect of IL
      4 alone and in combination with IL-1 beta on islet cells. For this purpose
      isolated rat pancreatic islets were cultured for 42 h in medium supplemented with
      0, 0.1, 1.0 or 10 ng/ml of human IL-4 in the absence or presence of 25 U/ml of IL
      1 beta during the last 24 h of culture. IL-4 alone dose-dependently decreased the
      islet glucose oxidation rate and the glucose-stimulated insulin release.
      Furthermore, the cytokine potentiated IL-1 beta-induced reduction in the islet
      DNA content and (pro)insulin biosynthesis rate. The medium nitrite accumulation,
      as an index of nitric oxide formation, was not influenced by IL-4 (10 ng/ml)
      alone, whilst IL-1 beta stimulation of medium nitrite was partly reduced by IL-4.
      Compared to the action exerted by IL-1 beta the inhibitory action of IL-4 on rat
      islet function was moderate, and the latter action seems to be independent on
      nitric oxide production.

PMID- 7640350
TI  - Expression of leukocyte chemotactic cytokines in myocardial tissue.
AB  - Cytotoxic action of leukocytes may be involved in the pathogenesis of
      inflammatory heart muscle disorders. We investigated the expression of rat
      leukocyte chemotactic cytokines--cytokine induced neutrophil chemoattractant
      (CINC) and JE--in cultured neonatal rat cardiac myocytes; CINC belongs to the
      interleukin 8 (IL-8) family and JE is a homologue of human monocyte
      chemoattractant protein 1 (MCP-1). In Northern blot analysis, CINC and JE
      transcripts were not clearly observed in unstimulated rat cardiac myocytes.
      However, their expression was clearly observed after exposure to tumour necrosis
      factor-alpha (TNF-alpha; 100 U/ml) for 2-6 h. We then evaluated IL-8 and MCP-1
      mRNA expression in human endomyocardial biopsy specimens from seven patients with
      idiopathic dilated cardiomyopathy by polymerase chain reaction analysis. Both IL
      8 and MCP-1 mRNA transcripts were recognized in all patients studied. These
      results show for the first time that leukocyte chemotactic cytokines, IL-8 and
      MCP-1, are expressed in myocardial tissue, which might contribute to the
      pathogenesis of inflammatory heart muscle disorders.

PMID- 7640351
TI  - Separation of AG function in floral meristem determinacy from that in
      reproductive organ identity by expressing antisense AG RNA.
AB  - The Arabidopsis floral homeotic gene AGAMOUS (AG) is a regulator of early flower
      development. The ag mutant phenotypes suggest that AG has two functions in flower
      development: (1) specifying the identity of stamens and carpels, and (2)
      controlling floral meristem determinacy. To dissect these two AG functions, we
      have generated transgenic Arabidopsis plants carrying an antisense AG construct.
      We found that all of the transgenic plants produced abnormal flowers, which can
      be classified into three types. Type I transgenic flowers are phenocopies of the
      ag-1 mutant flowers, with both floral meristem indeterminacy and floral organ
      conversion; type II flowers are indeterminate and have partial conversion of the
      reproductive organs; and type III flowers have normal stamens and carpels, but
      still have an indeterminate floral meristem inside the fourth whorl of fused
      carpels. The existence of type III flowers indicates that AG function can be
      perturbed to affect only floral meristem determinacy, but not floral organ
      identity. Furthermore, the fact that floral meristem determinacy is affected in
      all transformants, but floral organ identity only in a subset of them, suggests
      that the former may required a higher level of AG activity than the latter. This
      hypothesis is supported by the levels of AG mRNA detected in different
      transformants with different frequencies of distinct types of abnormal antisense
      AG transgenic flowers. Finally, since AG inhibits the expression of another
      floral regulatory gene AP1, we examined AP1 expression in antisense AG flowers,
      and found that AP1 is expressed at a relatively high level in the center of type
      II flowers, but very little or below detectable levels in the inner whorls of
      type III flowers. These results provide further insights into the interaction of
      AG and AP1 and how such an interaction may control both organ identity and floral
      meristem determinacy.

PMID- 7640352
TI  - A carrot cDNA encoding an atypical protein kinase homologous to plant calcium
      dependent protein kinases.
AB  - Calcium-dependent protein kinases (CDPKs) in plants typically contain a C
      terminal calmodulin-like domain with four EF-hand calcium-binding motifs. We have
      isolated a carrot somatic embryo cDNA clone which encodes a new, divergent
      isoform of this family, designated CRK (CDPK-related kinase). The catalytic
      domain of CRK shares a high degree of homology with the catalytic domains of
      plant CDPKs (53.5% average identity with its two closest phylogenetic relatives,
      CDPK431 (carrot) and AK1 (Arabidopsis). However, the C-terminal domain of CRK
      bears significantly less homology to calmodulin (22.0% identity to barley
      calmodulin) than other plant CDPKs (38.0% average identity between barley
      calmodulin and the C-terminal domains of CDPK431 and AK1). This degeneracy also
      involves the EF-hand motifs of CRK, which have diverged to varying extents. The
      predicted structure of CRK also contains an extended N-terminal domain 145 amino
      acids in length possessing a consensus N-myristoylation signal. CRK transcripts
      are most abundant in somatic embryos, with lesser accumulations in flowers and
      leaves and lowest levels in roots. Homologous genomic DNA sequences that
      hybridize with CRK cDNA but not with a carrot CDPK probe have been detected in a
      variety of higher plant taxa, including monocotyledonous species, suggesting that
      this CDPK-related kinase is widely conserved among angiosperms.

PMID- 7640354
TI  - Peroxisomal thiolase mRNA is induced during mango fruit ripening.
AB  - Fruit ripening is a complex, developmentally regulated process. A series of genes
      have been isolated from various ripening fruits encoding enzymes mainly involved
      in ethylene and cell wall metabolism. In order to aid our understanding of the
      molecular basis of this process in a tropical fruit, a cDNA library was prepared
      from ripe mango (Mangifera indica L. cv. Manila). By differential screening with
      RNA poly(A)+ from unripe and ripe mesocarp a number of cDNAs expressing only in
      ripe fruit have been isolated. This paper reports the characterization of one
      such cDNA (pTHMF 1) from M. indica which codes for a protein highly homologous to
      cucumber, rat and human peroxisomal thiolase (EC 2.3.1.16), the catalyst for the
      last step in the beta-oxidation pathway. The cDNA for the peroxisomal mango
      thiolase is 1305 bp in length and codes for a protein of 432 amino acids with a
      predicted molecular mass of 45,532 Da. Mango thiolase is highly homologous to
      cucumber thiolase (80%), the only other plant thiolase whose cloning has been
      reported, and to rat and human thiolases (55% and 55% respectively). It is shown
      by northern analysis that during fruit ripening THMF 1 is up-regulated. A similar
      pattern of expression was detected in tomato fruit. Wounding and pathogen
      infection do not appear to affect THMF 1 expression. The possible involvement of
      thiolase in fatty acid metabolism during fruit ripening will be discussed. To our
      knowledge this is the first report cloning of a plant gene involved in fatty acid
      metabolism showing an induction during fruit ripening.

PMID- 7640353
TI  - Characterization and expression of rpoC2 in CMS and fertile lines of sorghum.
AB  - A 165 bp deletion in the middle of rpoC2, the plastid gene which encodes the RNA
      polymerase beta" subunit, was identified in the small-anthered types of CMS
      sorghum, Sorghum bicolor (L.). Moench, containing A1, A2, A5, and A6 cytoplasms.
      It was previously shown that the amino acid sequence deleted in these CMS lines
      is in a monocot-specific region that contains several protein motifs that are
      characteristic of several transcription factors. Using primers flanking the
      deletion in PCR analyses, various types of CMS lines, some of which are used in
      hybrid sorghum production, were classified into two groups. CMS lines containing
      A1, A2, A5, A6 cytoplasms display the deletion in rpoC2. These lines have small
      anthers in which pollen development is arrested at an early stage and in which
      usually only empty exines are found. CMS lines containing A3, A4, and 9E
      cytoplasms do not possess the deletion. These lines have large anthers in which
      pollen degenerates at a later stage. Run-on transcription assays using 15
      chloroplast genes showed that chloroplast gene transcription rates are similar in
      CMS and fertile (maintainer and restorer) lines and F1 in seedling leaves.
      Analyses of RNA blots indicated that rbcL, rpoB and rpoC2 transcripts are
      accumulated mainly in the leaves and low in the inflorescence tissues and pollen.
      These data document plastid gene expression in leaves and non-photosynthetic
      tissues from CMS and fertile lines of sorghum.

PMID- 7640356
TI  - Organization, inheritance and expression of acetohydroxyacid synthase genes in
      the cotton allotetraploid Gossypium hirsutum.
AB  - The acetohydroxyacid synthase (AHAS) gene family of the cotton AD allotetraploid
      Gossypium hirsutum has been cloned and characterized. We have identified six
      different AHAS genes from an analysis of genomic clones and Southern blots of
      genomic DNA. Four of the six genes are organized as tandem pairs, in which the
      genes are separated by only 2-3 kb. Conservation of restriction fragment length
      polymorphisms between G. hirsutum and A-genome and D-genome-containing diploid
      cottons was sufficient to assign the single genes in clones A5 and A19 to the A
      and D subgenomes, respectively. Each diploid genome has one tandem pair, but in
      these cases we could not make specific subgenomic assignments. DNA and deduced
      amino acid sequences were determined for the A5 and A19 genes, and an AHAS cDNA
      clone isolated from a leaf library. The sequence of the A19 gene matches that of
      the cDNA clone, while the A5 gene is 97.8% similar. The four genes comprising the
      tandem pairs are much less similar to the cDNA clone. The deduced amino acid
      sequences of the mature polypeptides encoded by the A5 and A19 genes are
      collinear with the housekeeping forms of AHAS from Arabidopsis thaliana,
      Nicotiana tabacum and Brassica napus. The constitutive expression of A5 and A19
      was confirmed with RNase protection assays and northern blots. We conclude that
      these genes encode the main housekeeping forms of AHAS in G. hirsutum. Among the
      four AHAS genes comprising the two tandem pairs, at least two are functional.
      These genes exhibit either low-level constitutive expression (one or both of the
      'downstream' genes of each pair), or highly specific expression in reproductive
      tissue (one or both of the 'upstream' genes of each pair). The AHAS gene family
      of G. hirsutum is more complex than that of other plants so far examined.

PMID- 7640355
TI  - Transgenic analysis of the 5'- and 3'-flanking regions of the NADH-dependent
      hydroxypyruvate reductase gene from Cucumis sativus L.
AB  - The 5'- and 3'-flanking regions of HPRA, a cucumber gene that encodes
      hydroxypyruvate reductase, were evaluated for regulatory activity with respect to
      light responsiveness and organ specificity. To define the functional regions of
      the 5'-flanking region of HPRA, a series of deletions was generated and the
      remaining portions fused to the beta-glucuronidase (GUS) reporter gene (uidA)
      containing a minimal 35S promoter truncated at -90. The region from -66 to +39
      was found to be necessary for light-regulated expression of the uidA reporter
      gene, while the region from -382 to -67 was found to be necessary for its leaf
      specific expression. Further deletion of the HPRA 5' flanking region to -590
      resulted in high levels of root expression, suggesting the presence of a negative
      regulatory element responsible for silencing root expression of the HPRA gene
      between -590 and -383. The 3'-flanking region of the HPRA gene downstream of the
      polyadenylation site contains several sequence motifs resembling regulatory
      elements present in the promoters of several light-responsive genes. An 823 bp
      portion of the HPRA 3'-flanking region containing these putative regulatory
      elements enhanced GUS expression in leaves when placed downstream of the uidA
      reporter gene in the forward orientation, but not in the reverse orientation.
      When placed 5' of the -90 35S promoter, the 823 bp fragment enhanced slightly,
      independently of orientation, the root tip-specific expression pattern intrinsic
      to the -90 35S promoter, indicating that in some cases this region can act as a
      transcriptional enhancer.

PMID- 7640357
TI  - The S-locus of Nicotiana alata: genomic organization and sequence analysis of two
      S-RNase alleles.
AB  - Genomic clones encoding the S2- and S6-RNases of Nicotiana alata Link and Otto,
      which are the allelic stylar products of the self-incompatibility (S) locus, were
      isolated and sequenced. Analysis of genomic DNA by pulsed-field gel
      electrophoresis and Southern blotting indicates the presence of only a single S
      RNase gene in the N. alata genome. The sequences of the open-reading frames in
      the genomic and corresponding cDNA clones were identical. The organization of the
      genes was similar to that of other S-RNase genes from solanaceous plants. No
      sequence similarity was found between the DNA flanking the S2- and S6-RNase
      genes, despite extensive similarities between the coding regions. The DNA
      flanking the S6-RNase gene contained sequences that were moderately abundant in
      the genome. These repeat sequences are also present in other members of the
      Nicotianae.

PMID- 7640358
TI  - Isolation of cDNA clones of genes with altered expression levels in phosphate
      starved Brassica nigra suspension cells.
AB  - Differential gene expression at the transcriptional level was examined as an
      initial step in the investigation of the P(i) starvation response of Brassica
      nigra suspension cells. Total RNA was extracted from 7-day old cells grown in
      media containing either no P(i), 1.25 mM or 10 mM Pi. In vitro translation was
      carried out using their respective poly(A)+ RNA isolates and the resultant
      polypeptides were separated on a high-resolution SDS-PAGE gel. Scanning
      densitometry identified four polypeptides (ca. 31.7, 32.3, 52.5 and 64.8 kDa)
      present only in the P(i)-starved samples. Screening by differential hybridization
      was performed on a cDNA library constructed from mRNA isolated from P(i)-starved
      cells. Probes prepared from mRNA from P(i)-deficient and P(i)-sufficient cells
      identified a number of clones representing mRNA species that were preferentially
      transcribed under P(i) deficiency. These phosphate starvation-responsive (psr)
      clones were placed into eleven groups as determined by cross-hybridization.
      Northern blots showed that the corresponding genes are inducible in both mild and
      severe P(i) starvation conditions. Preliminary sequencing identified one of the
      clones as being homologous to beta-glucosidases from several plant species. The
      possible role of beta-glucosidase during Pi starvation and the identities of the
      other psr genes are discussed.

PMID- 7640361
TI  - Histone H3 transcript stability in alfalfa.
AB  - The stability of histone H3 transcripts in alfalfa for replication-dependent and 
      independent gene variants was measured by northern analysis under conditions of
      inhibition of transcription and/or translation. Replication-dependent histone
      H3.1 transcripts were about three-fold less stable than the equally
      polyadenylated mRNA for replacement variant H3.2 histone. In actively growing
      suspension cultures treated with dactinomycin half-lives of 2 and 7 h were
      observed for H3.1 and H3.2 mRNAs, respectively. mRNA stabilities were also
      measured indirectly by histone protein synthesis. The translation inhibitor
      cycloheximide strongly increased mRNA levels for both histone H3 variants. The
      dependence of histone mRNA turnover on translation in animals also appears to
      exist in plants. The combination of inhibition of transcription and translation
      by dactinomycin and cycloheximide was used in an indirect assessment of H3 mRNA
      stability throughout the cell cycle in partially synchronized and cycle-arrested
      cultures. Destabilization of replication-dependent histone H3.1 mRNA was detected
      in non-S phase cells.

PMID- 7640359
TI  - The Arabidopsis thaliana 4-coumarate:CoA ligase (4CL) gene: stress and
      developmentally regulated expression and nucleotide sequence of its cDNA.
AB  - An Arabidopsis cDNA clone encoding 4-coumarate:CoA ligase (4CL), a key enzyme of
      phenylpropanoid metabolism, was identified and sequenced. The predicted amino
      acid sequence is similar to those of other cloned 4CL genes. Southern blot
      analysis indicated that 4CL is single-copy gene in Arabidopsis. Northern blots
      showed that 4CL expression was activated early during seedling development. The
      onset of 4CL expression was correlated with the onset of lignin deposition in
      cotyledons and roots 2-3 days after germination. The timing of the expression of
      a parsley 4CL1-GUS fusion in transgenic Arabidopsis seedlings was examined in
      parallel and was very similar to that of endogenous 4CL. In mature plants,
      highest 4CL expression was observed in bolting stems, where relatively large
      amounts of lignin accumulate. Both 4CL and 4CL1-GUS mRNA accumulation was
      strongly and transiently activated by wounding of mature Arabidopsis leaves. 4CL
      expression was specifically activated within 6 h after infiltration of
      Arabidopsis ecotype Columbia leaves with a Pseudomonas syringae pv. maculicola
      strain harboring the bacterial avirulence gene avrB, which causes in incompatible
      interaction. The timing of 4CL activation was identical to the previously
      observed activation of PAL gene expression in this interaction. No activation of
      4CL expression was observed in a compatible interaction caused by a Pseudomonas
      syringae pv. maculicola strain without avrB.

PMID- 7640362
TI  - GA3-regulated cDNAs from Hordeum vulgare leaves.
AB  - The barley mutant dbg 576 shows an extreme vegetative dwarf phenotype. This is
      reversed after the application of GA3 which also induces the mutant florets to
      become partly fertile. cDNA clones ES1A and ES2A were isolated by differential
      screening with subtracted probes from a DNA library prepared from mutant leaf
      blades after GA3 treatment. Both the ES1A and the ES2A mRNA level increases as
      early as 30 min after GA3 treatment and decreases later. Accumulation of ES1A and
      ES2A mRNAs is leaf blade-specific and both are ca. 750 nucleotides long. ES1A
      encodes a protein of approximately 6 kD which shows a significant homology with
      mammalian epidermal growth factors (EGFs). ES2A encodes a protein of 22 kDa with
      homology, in regions with potential amphiphilic helices, with the D7 family of
      late embryogenesis-abundant proteins (LEA).

PMID- 7640364
TI  - Gerbera hybrida (Asteraceae) imposes regulation at several anatomical levels
      during inflorescence development on the gene for dihydroflavonol-4-reductase.
AB  - In the ornamental cut flower plant Gerbera hybrida the spatial distribution of
      regulatory molecules characteristic of differentiation of the composite
      inflorescence is visualized as the various patterns of anthocyanin pigmentation
      of different varieties. In order to identify genes that the plant can regulate
      according to these anatomical patterns, we have analysed gene expression
      affecting two enzymatic steps, chalcone synthase (CHS) and dihydroflavonol-4
      reductase (DFR), in five gerbera varieties with spatially restricted anthocyanin
      pigmentation patterns. The dfr expression profiles vary at the levels of floral
      organ, flower type and region within corolla during inflorescence development
      according to the anthocyanin pigmentation of the cultivars. In contrast, chs
      expression, although regulated in a tissue-specific manner during inflorescence
      development, varies only occasionally. The variation in the dfr expression
      profiles between the varieties reveals spatially specific gene regulation that
      senses the differentiation events characteristic of the composite inflorescence.

PMID- 7640365
TI  - Characterization of a low-temperature-induced cDNA from winter Brassica napus
      encoding the 70 kDa subunit of tonoplast ATPase.
AB  - A cDNA clone, pBN59, was isolated by differential screening of a cDNA library of
      winter Brassica napus during cold acclimation. Nucleotide sequence of BN59 was
      found to be homologous to that encoding the 70 kDa subunit of the vacuolar H(+)
      ATPase in plants. Transcripts hybridizing to BN59 accumulated during exposure to
      low temperatures and to the exogenous application of abscisic acid (ABA). Western
      blot analyses also indicated an increase in the 70 kDa subunit during cold
      acclimation. The accumulation of an endomembrane H(+)-ATPase is consistent with
      the observation of osmotic adjustment, increases in endogenous ABA and the
      proliferation of endomembranes during cold acclimation.

PMID- 7640366
TI  - Activity of constitutive promoters in various species from the Liliaceae.
AB  - In this paper we first review literature on the performance of various promoters
      in monocotyledonous species. In general, promoters isolated from monocots show a
      higher activity in monocot species. Moreover, the presence of an intron between
      the promoter and reporter gene increases transcription levels. We used the same
      approach to study gene expression in Liliaceae. The activities of the CaMV 35S,
      maize Adh1-based pEmu, rice Act1 and maize Ubi promoters, coupled to the beta
      glucuronidase (gus) reporter gene, were evaluated for transient gene expression
      upon particle bombardment of tissues of tobacco, rice, tulip, lily and leek.
      Although monocot promoters performed very well in rice tissues, the results of
      this study show that this cannot be generalized for other monocot species. The
      transcription inducing effects of monocot promoters were less pronounced or even
      absent in tissues of Liliaceae, while the presence of an intron between promoter
      and gus gene reduced promoter activity.

PMID- 7640363
TI  - A near-upstream element in a plant polyadenylation signal consists of more than
      six nucleotides.
AB  - A plant polyadenylation signal consists of three distinct components: a far
      upstream element (FUE) that can control utilization of several polyadenylation
      sites, one or more near-upstream elements (NUEs) that control utilization of each
      site in a transcription unit, and polyadenylation site (CSs) themselves. NUEs
      have previously been suggested to be related to the mammalian polyadenylation
      signal AAUAAA. However, many plant genes do not contain AAUAAA-like motifs near
      their polyadenylation sites. To better understand the nature of NUEs, we
      conducted a systematic analysis of the NUE for one polyadenylation site (site 1)
      in the pea rbcS-E9 gene; this NUE lacks an AAUAAA motif. Linker substitution
      studies showed that the NUE for site 1 in this gene resides in the sequence
      AAAUGGAAA. Single-nucleotide substitutions in this domain had modest effects on
      the functioning of this NUE. Replacement of part of this sequence with the
      sequence AAUAAA increased the efficiency of this NUE. However, alteration of
      nucleotides immediately 3' of the AAUAAA reversed this effect. Our results
      indicate that the NUE for site 1 consists of as many as 9 nucleotides, that these
      9 bases do not include an element that is intolerant of single base changes, that
      the sequence AAUAAA can function as a NUE for site 1, and that sequences flanking
      AAUAAA can affect the efficiency of functioning as a NUE.

PMID- 7640367
TI  - An S-RNase promoter from Nicotiana alata functions in transgenic N. alata plants
      but not Nicotiana tabacum.
AB  - Nicotiana tabacum and Nicotiana alata plants were transformed with genomic clones
      of two S-RNase alleles from N. alata. Neither the S2 clone, with 1.6 kb of 5'
      sequence, nor the S6 clone, with 2.8 kb of 5' sequence, were expressed at
      detectable levels in transgenic N. tabacum plants. In N. alata, expression of the
      S2 clone was not detected, however the S6 clone was expressed (at low levels) in
      three out of four transgenic plants. An S6-promoter-GUS fusion gene was also
      expressed in transgenic N. alata but not N. tabacum. Although endogenous S-RNase
      genes are expressed exclusively in floral pistils, the GUS fusion was expressed
      in both styles and leaves.

PMID- 7640368
TI  - Ultrastructural aspects of megakaryocyte/platelet system in essential
      thrombocythemia.
AB  - Six cases of essential thrombocythemia (ET) have been investigated in bone marrow
      as well as in blood cells. In majority of the cases, the bone marrow aspirate was
      hypercellular and presented an increased number of megakaryocytes, some of them
      with displastic appearance. The ultrastructural pattern of platelet peroxidase
      permitted us to identify atypic megakaryocytes and megakaryoblasts, particularly
      when present in pheripheral blood.

PMID- 7640360
TI  - Stress responses in alfalfa (Medicago sativa L.) XIX. Transcriptional activation
      of oxidative pentose phosphate pathway genes at the onset of the isoflavonoid
      phytoalexin response.
AB  - We have isolated cDNA clones encoding the pentose phosphate pathway enzymes 6
      phosphogluconate dehydrogenase (6PGDH, EC 1.1.1.44) and glucose 6-phosphate
      dehydrogenase (G6PDH, EC 1.1.1.49) from alfalfa (Medicago sativa L.). These
      exhibit extensive nucleotide and amino acid sequence similarity to the
      corresponding genes from bacteria, Drosophila and mammals. Transcripts encoding
      both enzymes are expressed at high levels in roots and nodules. Exposure of
      alfalfa suspension cells to an elicitor from yeast cell walls results in co
      ordinated increases in transcription rates for both genes, followed by increased
      steady state transcript levels but only slightly increased extractable enzyme
      activities, at the onset of accumulation of isoflavonoid phytoalexins. Levels of
      NADPH and NADP remain relatively constant in alfalfa cells following elicitation.
      The rapid transcriptional activation of 6PGDH and G6PDH does not therefore appear
      to be a response to altered pyridine nucleotide redox state. These genes appear
      to respond to early events in elicitor-mediated signalling rather than to
      subsequent elicitor-induced changes in secondary metabolism. Hydrogen peroxide, a
      potential signal for elicitation of anti-oxidative genes in biologically stressed
      plant cells, did not induce 6PGDH or G6PDH transcripts or enzymatic activity.

PMID- 7640369
TI  - Spindle and epithelioid cell nevus (Spitz nevus). Observation on nine cases.
AB  - Nine cases with spindle and epithelioid cell nevus occurred in children were
      analysed clinically and morphologically. The results indicate that Spitz nevus is
      composed of cells resembling those of a malignant melanoma. There are some
      morphological aspects such as: discontinuous junctional proliferation, the sparse
      mitotic activity, the process of maturation of the cells with increasing depth,
      considered as valuable markers for the benign character of this type of tumour.

PMID- 7640371
TI  - Histopathological and histoenzimological investigations of the rheumatoid
      articular cartilage.
AB  - Twenty seven biopsies of articular cartilage taken intraoperatively from patients
      with Rheumatoid arthritis (RA) and from control patients with traumas were
      examined using histopathological techniques (HE, VG, PAS-Alcian, Gomori,
      Safranine 0) and histoenzymological techniques (Acid phosphatase-lysomal marker,
      Chondroitinsulphatase, Peroxidase). Histopathologically, the rheumatoid articular
      cartilage appears with superficial and deep cartilaginous fissures, frequent
      perichondrocytic gaps associated with modification of the tinctorial activity. At
      the pannus synovia-cartilage junction we found invasive and destructive synovial
      inflammatory infiltrates penetrating and eroding the cartilage.
      Histoenzymologically, the rheumatoid chondrocytes have a high lysosomal potential
      (phosphatasic, chondroitinsulphatasic) and highly oxidative potential
      (peroxidasic) specific for lesion modifications.

PMID- 7640372
TI  - Delayed cell cycle kinetics and chromosome aberrations induced by girostan in
      human peripheral blood lymphocytes (PBL) in vitro. Note 1. Modified S-phase
      traverse.
AB  - Human peripheral blood lymphocytes (PBL) maintained in vitro for 72 hours were
      labeled with 5-Bromodeoxyuridine (BrdU) at 50 microliters/ml and concomitantly
      treated with girostan at 1.5; 2 and 2.5 micrograms/ml during the last 13; 11; 9;
      7; 5 and 3 hours before cells gathering for incorporation banding analysis in
      metaphase spreads. Similar untreated cultures, labeled with BrdU for the same
      time intervals were set up as controls in order to determine the phase of cell
      cycle traverse in the moment when girostan was given to the cultures. When
      compared with controls, incorporation banding pattern in treatment samples
      revealed the effect induced by girostan on cell cycle kinetics during different
      time intervals before mitosis. Cells with entirely dark chromosomes at metaphase
      [were] considered in G1/G2 phase, while metaphases with a clear banding on the
      chromosome were presumed to be at different moments within S-phase. Connected to
      the observed type of banding (R or G), early S, middle S and late S-phase
      metaphases were identified. A dose-related delay of cell cycle traverse was
      induced as revealed by the increased frequency of cells that lasted in S-phase
      and did not reach the G2-phase. More than that, within S-phase population, an
      evident accumulation of cells traversing middle S-phase was observed at the same
      time with the decrease of cells in late S. This effect of girostan on cell
      kinetics is also correlated with the moment during the cell cycle traverse when
      cytostatic treatment is gives.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7640373
TI  - Histologic comparative study on the relationships between dendrites and blood
      vessels in the central nervous system.
AB  - Histologic relationships between nerve cells and brain vessels have not been
      thoroughly studied yet. Golgi, in 1903, admitted the existence of specific
      linkage between brain dendrites and capillaries. We tried to discover the sites
      of dendro-vascular rapports and to compare their histology in rodents and lower
      vertebrates. The Golgi method and a histochemical method for ATPase (Wachstein
      and Meisel, 1957; Barka and Anderson, 1963) were used.

PMID- 7640374
TI  - Delayed cell cycle kinetics and chromosome aberrations induced by girostan in
      human peripheral blood lymphocytes (PBL) in vitro. Note 2. Chromosome
      aberrations.
AB  - Human peripheral blood lymphocytes (PBL) maintained in vitro for 72 hours were
      labeled with 5-Bromodeoxyuridine (BrdU) at 50 ug/ml and concomitantly treated
      with girostan at 1.5; 2 and 2.5 ug/ml during the last 13; 11; 9; 7; 5 and 3 hours
      before cells gathering to estimate the chromosome aberrations induced during
      different stages of cell cycle traverse as determined by incorporation banding
      pattern observed in metaphase spreads; similar untreated cultures but labeled
      with BrdU were set-up as controls in order to determine the phase of cell cycle
      traverse in the moment when girostan was given to the cultures. Chromosome
      aberrations were induced especially when treatments were performed 13 and 11
      hours before fixation. Their frequency was rather low (up to 7% of observed
      metaphases) and the lesions were not dose-related. When cells were treated during
      S- and G2-phases, chromatid and chromosome gaps, breaks, deletions and fragments
      were observed. Chromatid rearrangements as tri- or quadriradials were seen only
      when girostan was given during middle S-phase indicating that DNA breaking and
      misrejoining are successive steps during the same replication round. When cells
      were exposed to BrdU and girostan during the last 3 hours of incubation, no
      labeled metaphase or structural aberration was seen, but spiralization defects
      and premature separation of despiralated chromatids frequently appeared. This
      could indicate that the induction of chromosome condensing factor and of proteins
      responsible for normal centromere activity is disturbed when girostan treatment
      is applied during the last part of G2-phase, in the immediate proximity of
      mitosis.

PMID- 7640370
TI  - Giant congenital nevi. A clinical and histopathological study.
AB  - 17 cases of giant congenital nevi were reported. The lesions were located on the
      scalp, on the back and on the shoulders. The histopathological study revealed two
      cellular types of giant nevus; nevus cell type and neuroid type. Two types of
      neuroid structures were observed in neuroid type: Verocay bodies and pseudo
      Meissnerian corpuscles. The congenital nature of a benign nevus includes the
      presence of nevus cells, single or in nests within the follicular epithelium,
      eccrine ducts or glands. Essentially, all giant nevi show conspicuous nevic cell
      permeation not only of the reticular dermis but typically also of the subcutis
      and even the fascia.

PMID- 7640375
TI  - Fine needle aspiration of seminal vesicles: aspects of normal seminal cells.
AB  - Seminal vesicle cytology was studied in 18 patients admitted with diseases of the
      prostate, in whom fine needle aspiration by transrectal route was performed.
      Three cell-types are described: principal, basal and degenerative forms. Nuclear
      and cytoplasmic peculiarities of the principal and basal cells are revealed,
      discussing their value in the differential diagnosis from well-differentiated
      carcinoma of the prostate. It is emphasized the importance of pseudoatypical
      aspects of seminal cells--considered as a source for false positive results in
      FNAB of the prostate.

PMID- 7640376
TI  - Gliosarcoma cerebri with a myxoid matrix of the sarcomatous component.
AB  - A case of a cerebral gliosarcoma in a 63-year old female located in the left
      parietooccipital area of the brain is herewith described. Histology showed the
      tumour to consist of two components: a gliomatous resembling glioblastoma, and a
      sarcomatous with a prominent myxoid intercellular substance, a feature reported
      only thrice before in the medical literature. We report the histochemical and
      immunohistochemical characteristics of our case, and compare them with those of
      previous case reports.

PMID- 7640378
TI  - Extensive cutaneous lymphoma.
AB  - The case of a 35-years-old patient with a progressive and densely developed
      subcutaneous tumour comprising the whole right cervical and subcutaneous region
      is presented. The tumour was painless of pale brown and light red colour, with no
      adherence on the epidermis and subjacent muscles. The patient has no pathological
      symptoms. After the histopathological examination we found the dermal
      infiltration with small, round or oval hyperchromatic cells and the
      histoenzymological investigation revealed intense positive markers CLA and MB2
      pleading for their leukocytic nature while L26 reaction attested the B-cell
      nature of these lymphocytes and the diagnosis of polymorphous centroblastic
      malignant lymphoma (K type Working Classification).

PMID- 7640379
TI  - Wilms' tumor in the adult patient.
AB  - One documented case of Wilms' tumor in an adult patient is presented. The patient
      is diagnosed clinically with renal tumor, probably renal carcinoma. Wilms' tumor
      is extremely difficult to diagnose preoperatively in an adult patient. The
      pathologic hallmarks of this neoplasm are distinctive and it is histologically
      similar to the childhood tumor. The therapeutic guidelines and surgical
      principles governing childhood Wilms' tumor should be applied to adult Wilms'
      tumor. This patient is still alive after 15 months.

PMID- 7640380
TI  - Nucleolar organizer regions (AgNORs) in in situ and invasive components of breast
      cancers.
AB  - The authors have studied the nucleolar organizer regions (AgNORs) (which reflect
      the cell kinetic activity) in the in situ and invasive components of breast
      cancers. The mean number of AgNORs/nucleus was 4.18 (s.d.: 1.35) in the in situ
      compartments and 5.41 (s.d.: 1.90) in invasive areas. The difference between
      these two groups is statistically significant. The higher proliferative activity
      in the infiltrating component might be due to the interaction between epithelial
      cells and the supporting stroma.

PMID- 7640377
TI  - Rare palpebral tumours. Histopathological aspects.

PMID- 7640381
TI  - Rethinking nursing's basic competencies.
AB  - An increasing tendency to focus primarily on the intellectual and technical
      competence of nurses is radically redefining nursing and threatening nursing's
      ability to respond to human need. After exploring why interpersonal skills and
      moral competence are essential to the practice of nursing, the article describes
      practical strategies to develop interpersonal competence and challenges nurses to
      hold themselves and one another accountable for interpersonal proficiency. The
      discussion redirects nursing's attention to the human outcomes of nursing and
      health care.

PMID- 7640382
TI  - Nurse caring and the new health care paradigm.
AB  - The current health care environment has ignited a renewed interest in the value
      of nurse caring and its potential effect on quality of care and patient
      satisfaction. This study compared perceptions of nurse caring behaviors of
      inpatient hospice nurses and the families of inpatient hospice clients. The
      Professional Caring Behaviors Instrument was administered to staff nurses and
      family representatives in the hospice of a midwestern hospital. Perceptions of
      nurse caring behaviors were similar for both groups. Only one item. "The caring
      nurse respects the patient's spiritual beliefs," was significantly more important
      to the nurses than the family members. Several differences in perceptions were
      noted in relationship to age.

PMID- 7640383
TI  - Synchronous connections: nursing's little secret.
AB  - As nurses prepare for their place in health care reform, it is becoming more
      important than ever to be clear about the unique contribution nurses make to
      health care outcomes. In our technology-driven society, however, some of
      nursing's most powerful contributions go unacknowledged. An unexpected finding of
      a study on nurse experts' perceptions of synchrony revealed that nurses
      themselves frequently do not document or even dialog about important
      contributions if they cannot be captured within the dominant paradigm of high
      technology care. The article describes nurses "little secret" that must be
      exposed.

PMID- 7640384
TI  - Perceptions of a dying patient of the quality of care and caring: an interview
      with Ivan Hanson. Interview by June A Schmele.
AB  - As a health care professional for many years, Ivan Hanson was an advocate of
      quality health care and the caring component. As a health care consumer during
      his nearly 5-year struggle with cancer, he had ample opportunity for thoughtful
      reflection about this same care and caring. During the last stage of his illness
      he willingly shared his reflections about important aspects of the quality of
      care from the consumer's perspective. He leaves this as a legacy that has the
      potential to influence the caring dimension of the services that nurses provide.

PMID- 7640385
TI  - Watson's theory of caring: a model for implementation in practice.
AB  - Jean Watson's theory of human caring in nursing is introduced as an innovative
      approach to improving care for residents in a special dementia unit. The
      rationale for theory-based nursing practice includes implementation projects of
      caring theory that have increased job satisfaction among staff, shortened
      hospital length of stay, and reduced health care costs. Specific examples of ways
      that Watson's model can be applied in typical nurse-client situations are
      presented. Implementation strategies with creative visual aids are included, and
      research tools for the evaluation of outcomes are described.

PMID- 7640386
TI  - Caring for the nurse self: verbal abuse as a case in point.
AB  - An assumption that undergirds quality improvement activities is that a
      practitioner cares for himself or herself. The article describes six caring
      attributes. The discussion focuses on care of the nurse self with verbal abuse as
      a case in point. Nurses average five to six incidents of verbal abuse every
      month. Understanding oneself and implementing certain techniques can help one
      overcome feelings of powerlessness, incompetence, and decreased self-worth. Self
      knowledge and self-change are important aspects of the nurse caring for himself
      or herself. Quality nursing practice is a positive outcome.

PMID- 7640387
TI  - A simultaneous analysis of nursing care quality and cost.
AB  - The simultaneous evaluation of quality and the cost of health care can provide
      information that is useful for guiding quality improvement activities while
      minimizing or reducing cost. Despite the evidence of concern for health care
      costs, a long history of concern for health care quality, and numerous efforts to
      evaluate the quality and cost of health care simultaneously, current methods have
      been relatively ineffective in decreasing or containing costs. Simultaneous
      monitoring of cost and quality indicators can be used to compare differences
      between the cost of prevention and the cost of failure and can be utilized to
      determine areas where failure costs can be decreased.

PMID- 7640388
TI  - Quality improvement in action: development of a tool.
AB  - Based on findings of the Utilization/Peer Review Forum, a quality assurance
      system committee comprising public health professionals, there was a question
      about whether public health nurses followed the standards of care when treating
      children with anemia. The article describes the process of identifying the
      problem and then developing and implementing an investigation to determine the
      magnitude of the problem. A sample of 703 child care records was audited. As a
      result of this process, conflicts in the established protocols of the county
      health department were identified, and an unexpectedly high prevalence of
      childhood anemia was discovered.

PMID- 7640389
TI  - Continuous quality improvement in the neonatal intensive care unit: evaluating
      parent satisfaction.
AB  - A comprehensive approach to the delivery of family-centered care in the neonatal
      intensive care unit (NICU) requires that parental perceptions of caregiving be
      addressed. The Parent Feedback Questionnaire is based on researched needs of NICU
      parents. Specific dimensions of needs (informational, emotional, parenting, and
      environmental) and overall satisfaction are identified and included in survey
      items. Ongoing feedback from parents is obtained and incorporated into a planned
      multidisciplinary continuous quality improvement program. Evaluation of data has
      resulted in planned interventions to reduce sources of stress and dissatisfaction
      for parents.

PMID- 7640390
TI  - Caring in the nursing profession is being forgotten.

PMID- 7640391
TI  - Diadenosine polyphosphates: their biological and pharmacological significance.
AB  - Diadenosine polyphosphates are members of a group of dinucleoside polyphosphates
      that are ubiquitous in bacteria to mammals. In recent years, the diadenosine
      polyphosphates have received considerable attention in view of their multiple
      biological activities and potential pharmacological activities. Diadenosine
      polyphosphates have been identified as modulators of cardiovascular and
      neurotransmitter-like activities in recent years, besides their previously
      described role in cell proliferation and as signal molecules when cells are
      undergoing stress. Diadenosine polyphosphates and their synthetic analogues are
      being evaluated for their potential as pharmacological agents. This article
      discusses the various biological functions and physiological significance of the
      diadenosine polyphosphates.

PMID- 7640392
TI  - Computer analysis of the migrating motility complex of the small intestine
      recorded in freely moving rats.
AB  - Myoelectric activity of the small intestine was recorded digitally in fasted,
      freely moving rats fitted with multiple pairs of electrodes in the
      antimesenterial smooth muscle. The electrodes were implanted under strict aseptic
      conditions to safeguard the animal's health and thereby benefit experimental
      results. As in many other mammalian species, the fasted electrical and mechanical
      activity of the small intestine in the rat consists of alternating periods of
      activity and quiescence jointly called the Migrating Motility Complex (MMC).
      Existing methods for the analysis of small bowel myoelectric activity either
      integrate spike activity over longer periods of time or describe characteristics
      of single bursts. We have developed a computer program for fast, automated
      analysis that distinguishes the three characteristic phases of the MMC. The
      computer program recognizes periods of varying spike burst frequency and then
      produces a graphical and numerical output of the length and mean burst frequency
      of the different phases of each MMC that correlates well with the results of
      visual evaluation. The techniques used are discussed in relation to existing
      recording and analysis methods, and specific decisions in the program are
      motivated. The system will be a useful tool in assessing the effects of drugs,
      peptides, or stress on small bowel motility.

PMID- 7640393
TI  - Calculating slope and ED50 of additive dose-response curves, and application of
      these tabulated parameter values.
AB  - Comparing dose-response curves (DRCs) of a compound A in the absence and presence
      of a fixed dose of an antagonist B is standard in pharmacology and toxicology.
      When B qualitatively resembles A in its action, it is often useful to construct
      theoretical DRCs of additive and independent combinations. Theoretical curves are
      calculated from experimental values by the program ALLFIT, which uses the four
      parameter logistic equation. DRCs of theoretical, additive DRCs are obtained by
      using the respective values for slope and ED50, which were taken from tables
      presented here compiled on the basis of the slope of the DRC of A alone (0.6-14)
      and of the effect of B alone (1-75%). These tables are unnecessary for the
      construction of theoretical curves if A acts by an independent mechanism, giving
      values for slope and ED50 identical to those of the DRC of A alone. Experimental
      DRCs of antiviral and other effects (the latter taken from data in the
      literature) are compared with theoretical curves by an F-test analysis provided
      by ALLFIT. The method can be used successfully for the construction of
      theoretical curves for additive and independent DRCs and comparison with
      experimental curves. This comparison may help clarify the mode of interaction of
      A with B.

PMID- 7640394
TI  - Measuring the weight of the isolated perfused rat lung during negative pressure
      ventilation.
AB  - Weight measurement represents a means of quantitating edema formation in isolated
      lungs and following its time course. During ventilation by negative pressure
      measurements with commonly used weight transducers are impossible because the
      pressure changes inside the artificial thoracic chamber affect the weight
      reading. Therefore, we have developed a weight transducer that can be used during
      negative pressure ventilation. Its design and applicability for assessing weight
      gain induced by various agents in the negative-pressure-ventilated isolated
      perfused rat lung is presented here.

PMID- 7640396
TI  - Mechanical and contractile properties of in situ localized mesenteric arteries in
      normotensive and spontaneously hypertensive rats.
AB  - An in situ model was developed for studying mechanical properties of mesenteric
      arteries in rats. A branch of the mesenteric artery was exposed and dissected in
      normotensive (WKY) and spontaneously hypertensive rats (SHR). A catheter was
      introduced into the larger branch of the mesenteric artery and connected to a
      pressure chamber. The artery was submitted to transmural pressures ranging from 0
      to 200 mmHg per steps of 25 mmHg and observed using a microscope-video-camera
      system. The diameter-pressure relations were established under basal conditions,
      under contraction (phenylephrine 10(-6) M), and after abolition of the smooth
      muscle tone by potassium cyanide (KCN, 0.1 mg/mL). The arterial segment was then
      fixed (glutaraldehyde 2.5%), and the wall cross-sectional areas were measured in
      transverse sections. Compliances, distensibility, wall tensions, and wall
      stresses were calculated from diameter, pressure, and media thickness values
      under three conditions. Active tension and active stress were defined as
      differences in wall stresses and wall tensions calculated under passive and
      active conditions. Comparison of WKY and SHR when arteries were studied at the
      respective operating pressure indicates (1) thicker and stiffer mesenteric
      arteries in SHRs than in WKY rats, (2) similar wall stresses in mesenteric
      arteries from WKY and SHRs despite larger wall tensions in the hypertensive
      group, and (3) larger contractility to phenylephrine in SHRs than in WKY
      mesenteric arteries.

PMID- 7640395
TI  - The application of the human beta-globin gene locus control region and murine
      erythroleukemia cell system to the expression and pharmacological
      characterization of human endothelin receptor subtypes.
AB  - The cDNAs encoding both A and B subtypes of the human endothelin receptor have
      been inserted into mammalian cell expression vectors that utilize the human
      globin gene, locus control region. These constructs have been introduced into
      murine erythroleukemia cells and inducible high level expression of the receptors
      has been achieved (approximately 1.5-pM/mg membrane protein and approximately
      13,500 binding sites/cell for both receptor subtypes). Cell lines expressing
      these receptors were obtained on a rapid time scale (3-4 weeks), facilitated by
      the need for the analysis of only small numbers of cell clones/receptor
      (approximately 6). Competitive binding assays with endothelin-1 gave IC50s of 130
      +/- 30 pM for endothelin-A receptor and 160 +/- 30 pM for endothelin-B receptor.
      Similar studies with the different isoforms of endothelin, sarafatoxin-S6b and 
      S6c, BQ123 and BQ3020, all gave the expected selectivity profiles. The IC50s for
      all compounds were in close agreement with those reported for native receptors.
      Thus, this expression system, which has several advantages over other described
      expression systems, is capable of rapidly providing large quantities of receptor
      for detailed pharmacological analyses or drug screening. In addition, the
      expressed receptors display the expected pharmacological profiles in the absence
      of any complicating, competing interactions from other subtypes or binding sites.

PMID- 7640397
TI  - Storage-phosphor autoradiography: a rapid and highly sensitive method for spatial
      imaging and quantitation of radioisotopes.
AB  - This study evaluates a storage-phosphor imaging system for rapid autoradiography
      and quantitation of beta- and gamma-ray emitters in mice. Known quantities of
      authentic 3H, 14C, and 195mPt (0.06 to 31,714 DPM/mm2) were exposed to imaging
      plates of the storage-phosphor system for 0.5 min to 15 hr at room temperature.
      Immediately after exposure, the imaging plates were scanned and the
      autoradiograms were quantified. Radioactivity as low as 1.8 DPM/mm2 (3H), 0.06
      DPM/mm2 (14C) and 3.1 DPM/mm2 (195mPt) was visualized and quantified in 8 hr (3H
      and 14C) and 6 min (195mPt), respectively. The system displayed a linear range of
      four to five orders of magnitude (14C: 0.5 to 6,914 DPM/mm2 for 2-hr exposure;
      3H: 1.8 to 15,372 DPM/mm2 for 15-hr exposure; and 195mPt: 66 to 198,000 DPM 6 min
      exposure). Variation from scan-to-scan was small (< 1% to 5%) and was more
      pronounced at the lower detection limits and exposure periods. Similar
      sensitivity, linearity, and variability were obtained in cryosections of murine
      tumors treated with 14C-fluorouracil or 3H-epinephrine and whole-body
      autoradiograms of mice treated with 195mPt-cisplatin via liver. The high
      sensitivity allowed noninvasive imaging of live unanesthetized mice treated with
      195mPt with a short exposure time (105 sec). These results validate, for the
      first time, the high sensitivity, linearity, and wide dynamic range of storage
      phosphor technology for quantitative autoradiography of 14C, 3H, and 195mPt
      isotopes. Storage-phosphor imaging will be useful in rapid quantitative
      autoradiographic disposition studies of radiolabeled drugs and excipients in
      vitro and in vivo.

PMID- 7640398
TI  - Myocardial mitogenic effect of erythropoietin through the activation of Na(+)
      K(+)-ATPase activity.
AB  - Erythropoietin is considered unique among the hematopoietic growth factor with a
      specific action on the differentiation and proliferation of erythroid progenitor
      cells. We have observed a dose-dependent modulatory action of human recombinant
      erythropoietin (rHuEpo) stimulated the rate of cell growth but at higher ones (3
      10 U/ml) inhibited it. The mitogenic action of the hormone is correlated with
      cardiac membrane Na(+)-K(+)-ATPase activity since concentrations of rHuEpo that
      increased cell growth stimulated paranitrophenilphosphatase (pNPPase) activity,
      while those concentrations that inhibit the enzyme markedly bloqued its mitogenic
      action. Moreover, ouabain (10(-5) M), concentration that inhibits Na(+)-K(+)
      ATPase activity, blunted the stimulatory action of rHuEpo on cell proliferation.
      We also demonstrated that rHuEpo while activated the cardiac membrane Na(+)-K(+)
      ATPase was able to alter the contractile action of ouabain on isolated neonatal
      rat atria. Indeed rHuEpo (1 U/ml) enhanced the non toxic action of the cardiac
      glycoside attenuating and delaying the onset of the toxic effect of the drug.
      These results show that rHuEpo has a non hematopoietic cardiac effect, associated
      with the cardiac Na(+)-K(+)-ATPase activity, that regulates the myocytes growth
      and the biological action of cardiac glycosides on isolated rat myocardium.

PMID- 7640399
TI  - Influence of pirenzepine on colonic serotonin changes induced by short chain
      fatty acid.
AB  - In this work we have demonstrated the influence of a short chain fatty acid
      (acetate) on the number of enterochromaffin (EC) cells containing serotonin
      (5HT), at two different pH (pH 6.9 absorptive stimuli, and pH 2.9 secretory
      stimuli), infused into the colon during one hour. The number of EC cells decrease
      significatively, specially in the cecum with a solution of low pH (2.9). The
      action of piprenzepine in preventing this reduction demonstrated that was partly
      mediated by a cholinergic receptor mechanism. On the other hand, a decrease on
      the release of 5HT to the lumen was a observed under the influence of
      pirenzepine. We conclude that the short chain fatty acid acetate, at a low pH
      induces the release of serotonin through a cholinergic mechanisms indicated by
      the inhibition observed with antimuscarinic drug.

PMID- 7640401
TI  - On the phasic reflex bronchodilation in the cat.
AB  - In records of tracheal pressure or flow taken from anesthetized cats appear large
      pressure-negative, or air inflow excursions, in response to single pulses applied
      to the central end of the vagus nerve. These responses have been attributed to
      phasic bronchodilation and not only due to the brief contractions of inspiratory
      muscles that occur as part of the total responses. Phasic bronchodilation
      responses appear mainly during inspiration but they may also occur in the
      expiratory phase through facilitation, during post-hyperventilatory apnea or that
      induced by constant current (d.c.) vagal stimulation. They are significantly
      reduced after lung sympathectomy. These bronchomotor responses showed long term
      depression (LTD) after spontaneous or reflexly evoked hiccups, and long term
      potentiation (LTP) after repetitive, or d.c. vagal stimulation. They are also
      potentiated on the experimental conditions that include exaggerated sympathetic
      activity. These and some other characteristics described indicate that
      bronchomotor responses are legitimate and can be used to follow the changes in
      excitability of the central generator of breathing.

PMID- 7640400
TI  - Influence of anterodorsal thalamic nuclei on adrenal function in rats.
AB  - Experiments were carried out in order to elucidate a possible role of
      anterodorsal thalamic nuclei (ADTN) upon adrenal gland function in rats.
      Bilateral stimulation of ADTN produced a significant decrease in corticosterone
      concentration (C) in both plasma and adrenal tissue. After exposure to ether
      vapour, rats with bilateral lesion of ADTN showed that the increase in plasma C
      was markedly higher than that in the sham lesioned ones. Sham-lesioned stressed
      rats showed values of adrenal C higher than the values in sham unstressed rats.
      Whereas, ADTN-lesioned rats showed that adrenal C values were significantly lower
      than in the lesioned unstressed rats. The concentration of adrenal
      catecholamines, norepinephrine (NE) and epinephrine (E), in sham-lesioned rats
      was unaffected by ether stress. In stressed lesioned rats, adrenal glands
      contained 4 times as much NE and 2 times as much E as did the adrenal glands from
      lesioned unstressed rats. Our results suggest that the ADTN exert and inhibitory
      effect on adrenocortical function. They would involved in mediating the effect of
      stress in adrenal cortex and medulla in rats.

PMID- 7640402
TI  - Precise measurement of bone mineral density in rats using dual-energy X-ray
      absorptiometry.
AB  - The dual X-ray absorptiometer (DEXA, Hologic ZDR-1000) in a high resolution mode
      was evaluated for measuring: Area (A), Bone Mineral Content (BMC) and Bone
      Mineral Density (BMD) in femur and tibia of adults rats at four regions: proximal
      (L1), diaphysis (L2-L3) and distal (L4). Reproducibility with and without
      repositioning was evaluated in femur after ten measurements in a water bath at
      depths between 2.0 and 2.5 cm. The whole coefficient of variation (CV = 100 x
      SD/mean) of BMD was 0.52% and 0.47% respectively. Accuracy was evaluated by
      comparing the BMC to bone ash weight. BMC was highly correlated with chemical
      analysis (r = 0.98, p < 0.001) for femur. The ability to detect changes in BMD
      was studied by comparing BMD of the right and left femurs and tibias of adult
      normal males and females rats. No significant differences were found between both
      sides. Nevertheless, when BMD (X +/- SE) of male and female rats were compared,
      female rats presented lower BMD at distal femur (0.263 +/- 0.021 vs. 0.315 +/-
      0.009, p < 0.05) and proximal tibia (0.259 +/- 0.016 vs. 0.315 +/- 0.013 p <
      0.02) than male rats. We also studied the ability to detect BMD changes in
      abnormal metabolic conditions. SHAM operated rats were compared to ovariectomized
      (OVX) rats and it was observed that femur of OVX showed a lower distal BMD than
      SHAM (0.217 +/- 0.005 vs. 0.263 +/- 0.021, p < 0.05). In summary, DEXA is a
      technique accurate and precise enough to detect changes on BMC and BMD in small
      animals permitting the experimental study of different metabolic bone conditions.

PMID- 7640405
TI  - Basal and paracetamol-depleted glutathione from human lymphocytes: ethnic
      variability.
AB  - Glutathione (GSH) combines with several xenobiotics and its electrophilic
      metabolites enhancing their elimination in bile and urine. Thus protects cells by
      preventing binding of these labile intermediary with vital molecules. Some
      individuals may be susceptible to this deleterious effect according to the
      intracellular GSHB concentration. In the present study we intend to determine the
      extent and nature of interindividual variation of human lymphocyte glutathion
      contents, after oxidative stress with paracetamol. Intracellular basal GSH was
      measured after one hour of incubation in a cell culture medium additioned with
      rat liver microsomes and NADPH at 37 degrees C. Each time two batches of
      lymphocytes were measured in parallel, one without paracetamol (basal) and the
      other with paracetamol (paracetamol-depleted). In 90 normal adult Caucasians,
      mean basal GSH concentration of lymphocytes (22.3 mumol/10(7) cells) were higher
      than in a comparable group of 20 Chinese (19.1 mumol/10(7) cells) or 20 Blacks
      (17.9 mumol/10(7) cells) subjects. Paracetamol treated lymphocytes were depleted
      of GSH at the same rate in each group, thus the same differences seen in basal
      conditions persist post oxidative stress. Probit analysis of values for each
      ethnic group revealed only a single mode. In otherwise normal Caucasians males
      with Down's syndrome, mean basal GSH concentration (29.7 mumol/10(7) cells) were
      higher than those of Caucasians, Chinese and Blacks.

PMID- 7640407
TI  - Morphological and morphometrical features of the corpus albicans in the course of
      the postmenopausal period.
AB  - Studying the morphological and morphometrical aspects of corpora albicantia at
      different phases of the postmenopausal period, the authors observed that, until
      five years after menopause, the fibroblasts were developed, and later in this
      period of life, the number and activity of these cells are diminished. It is
      suggested that the description of corpora albicantia in atrophic ovaries of
      postmenopausal women occurs owing to a decrease of remodelling fibroblastic and
      macrophagic activity, or connective tissue substitution, made by these cells
      under physiological conditions.

PMID- 7640403
TI  - Physiological studies in the South American camelid llama (Lama guanicoe f. d.
      glama). I. Body water spaces and water turnover.
AB  - Body water (BW) and extracellular water (ECW), were determined with tritiated
      water (THO) and 82Br injected into the vein, to 8 mature animals of both sexes
      during the winter season. The biological half-time of THO (T1/2 THO) and the
      daily water turnover (WT) were measured and the intracellular water (ICW)
      calculated. The studies with THO were repeated in the same animals and in 2
      lactating females in spring and summer. Two calves were also studied during
      spring. The values obtained in winter were: BW 659 +/- 12 ml/kg; T1/2 THO 9.2 +/-
      1 day; WT per 24 h 50 +/- 3 ml/kg or 116 +/- 5 ml/kg 82 and 163 +/- 9 ml per 1 of
      BW82; ECW 215 +/- 8 ml/kg or 32.5 +/- 3% BW; ICW 447 +/- 12 ml/kg or 67.7 +/- 4%
      BW. The results of the spring's studies showed a significant increase in the
      values of WT. In summer a further increment of this parameters was observed when
      expressed as ml/kg body solids. This differences were remarkable in those in
      lactation. The proportion of water in the body was significantly higher during
      summer in all animals. BW in lactating animals during summer was 783 +/- 9 ml/kg
      and in the other animals 718 +/- 18; T1/2 THO values were 3.3 +/- .-06 and 4.5 +/
      .4 day, respectively. WT was 396 +/- 9 ml/kg.82 or 484 +/- 8 ml/l BW82 in the
      lactating animals and 260 +/- 9 ml/kg 82 or 341 +/- 12 ml/l BW82 in the other
      animals.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7640404
TI  - [Effects of hydrocortisone on acid secretion in the isolated toad gastric
      mucosa].
AB  - The effects of steroids on gastric acid secretion have been studied in different
      animal species with contradictory results. In the present work we investigated
      direct effects of hydrocortisone on acid secretion in the isolated toad gastric
      mucosa (Bufo marinus). The rate of hydrogen ion secretion (QH+) was measured
      using the pH-stat method of Durbin and Heinz. Hydrocortisone significantly
      stimulated QH+ in a dose dependent manner. The effect tended to reach a maximum
      with the concentration of 10mM and lasted for at least one hour. In the mucosa
      pre-treated with 1mM cimetidine, an specific antagonist of histamine H2
      receptors, the addition of 10mM hydrocortisone did not stimulate QH+, but
      addition of the cholinergic agonist carbachol did produce a significant
      stimulation in the rate of acid secretion. In the gastric mucosa previously
      stimulated with 5mM hydrocortisone, the addition of a submaximal dose of
      histamine increased QH+ and this effect was greater than that provoked by
      histamine in the absence of the steroid. The results indicate that hydrocortisone
      significantly stimulates acid secretion in a dose-dependent manner in the
      isolated toad gastric mucosa. This effect seems to be dependent on the activation
      of H2 receptors.

PMID- 7640406
TI  - [Analysis of restraint of the femur head. Experimental study of allograft of cold
      bone and autoclaved bone to kill the HIV virus].
AB  - The retrovirus S.I.A.D. grown in marrow bone and iatrogenic infections may be
      possible after bone graft in following total hip arthroplasties. Previous
      investigators proposed several methods to kill the virus, but without
      bacteriological safety. They found 20 to 55% of loss on mechanical properties.
      The present study reports the response of autoclaved femoral heads compression
      testing on material machine Model 1026 Instron. The stress response of marrow
      bone to stains showed a classic peak and with linear regression study we saw a
      relationship between autoclaved bone and cold bone. The cortical bone resists to
      strains highly 12% of load.

PMID- 7640408
TI  - Variations in the anatomical organization of the human aortic arch. A study in a
      Portuguese population.
AB  - We have studied the anatomical features of human aortic arches in a sample of the
      Portuguese population using postmortem measurements of the arches and their
      branches in 33 cadavers. We found that there is a significant minority of
      individuals (18% of the total) who did not present the usual 3-branched aortic
      arch; interestingly, all 2-branched arches were seen in women and all 4-branched
      arches were observed in men. The arterial branches could spring either from the
      ascending segment of the arch (61% of total) or from its horizontal segment (39%
      of total). Our measurements showed that the springing of the branches was
      associated with the narrowing of the aortic arch, so that the difference in the
      diameter of the aortic arch between the origin of the first and last branches
      could reach up to 11 millimeters. We found that the relative caliber of the
      arterial branches of the aortic arch depended on the position of its origin at
      the arch: in aortic arches with branches that were originated at the horizontal
      segment of the arch the first arterial branch was always the widest of the three,
      whereas in aortic arches with branches coming out at the ascending segment of the
      arch the widest arterial branch was the third one. Our data support the view that
      there is a wide spectrum of variations in the anatomical arrangement of the
      aortic arch in humans, and offer information on the prevalence of aortic arch
      variations in a Portuguese population.

PMID- 7640409
TI  - Cell kinetics of the human mammary lobule during the proliferative and secretory
      phase of the menstrual cycle.
AB  - We evaluated the mitotic index and nuclear volume of the epithelium of the human
      mammary lobule during the menstrual cycle. Thirty patients were selected and
      divided at random into two groups, i.e., 15 women in the proliferative phase and
      15 in the secretory phase. Normal mammary tissue was obtained on the occasion of
      fibroadenoma enucleation. Mitotic indices (/1000) and nuclear volume (micron 3)
      were 0.0 and 53.8, respectively, during the proliferative phase, and 11.6 and
      130.0, respectively, during the luteal phase, the difference being statistically
      significant (p < 0.05). These data indicate that the proliferative stimulus of
      the mammary lobule is more intense during the luteal phase of the normal cycle
      and may probably be due to a synergistic action between progesterone and
      estradiol.

PMID- 7640411
TI  - Development of the axial cartilaginous skeleton in the regenerating tail of
      lizards.
AB  - In order to study the pattern of growth of regenerating cartilage, H3-thymidine
      was injected in individuals of the lizards Anolis carolinensis and Lampropholis
      delicata during advanced stages of tail regeneration. Light and electron
      microscopic autoradiographical analysis showed that the regenerating
      cartilaginous tube was mostly derived from the interstitial proliferation of
      chondroblasts. Appositional growth is limited during the initial stages of
      cartilage formation. Later, after the differentiation of an inner and outer
      perichondrium, a few cells were added to the cartilaginous tube while cellular
      degeneration of the calcifying areas was in progress. In this way a constant
      diameter of the cartilaginous tube was maintained. In order to study the rate of
      production of matrix protein (collagen), H3-proline was administered to other
      samples of Lampropholis. To the best of the author's knowledge this was done for
      the first time in the cartilage of a reptiles. The tracier was mostly localized
      in the apical-intermediate cartilage and one hour postinjection it was mostly
      concentrated in the ergastoplasm around the Golgi apparatus and its secretory
      vesicles. Three hours after the injection of H3-proline some of the tracier was
      found in the cytoplasm of chondrocytes and in the extracellular matrix.

PMID- 7640410
TI  - [Angiographic study of collateral circulation in coronary occlusion].
AB  - To define the collateral circulation pathways between coronary arteries, 101
      coronarographies of patients who had at least one occlusion of a coronary artery
      (left-anterior descending artery, circumflex, right coronary) were analysed. We
      found 12 collateral pathways for the right coronary, 8 for the anterior
      descending artery, and 4 for the circumflex artery. These collateral circulation
      pathways have been mapped and compared to those of literature.

PMID- 7640413
TI  - [The intervertebral disk. Attempt at a "finite element" model].
AB  - Intervertebral disk composite model is unsatisfactory definite in biomechanical
      behaviour despite multiples technics used. Using histologic and histoenzymology
      it's possible to determinate proportions of collagen fibers in the different
      parts of the disk. A trustworthy finite element 3D model is proposed and tried by
      real experiments.

PMID- 7640412
TI  - An important anatomic variation in head and neck region: anomaly of the anterior
      belly of the digastric muscle.
AB  - Anomalies of the anterior belly of the digastric muscle are not very rare. An
      anomaly in this region may have clinical significances. In this study, bilateral
      anomalies of the anterior bellies of both digastric muscles are presented. When
      an asymmetry in the floor of the mouth is detected during diagnostic procedures
      like radiologic studies, anomalies of the anterior belly of the digastric muscle
      should also be considered besides other reasons of asymmetry. Additionally,
      possible occurrence of this kind of anomalies should be remembered during
      surgical procedure involving this region.

PMID- 7640414
TI  - Dialysis in acute renal failure--muddying the waters.

PMID- 7640415
TI  - "Junk science" in the courtroom. Causes and effects.

PMID- 7640416
TI  - The refrigerated dialysis situation.

PMID- 7640417
TI  - Reprocessing of reusable medical devices.
AB  - Advances in medical science and, in particular, minimally invasive surgical and
      diagnostic procedures have stimulated the development of new and improved medical
      devices. This has been made possible because of developments in engineering and
      material sciences. The design of devices for reusability is particularly
      important in an effort to provide cost effective healthcare. Concerns and issues
      include the ability to safely and effectively reprocess the devices, infection
      prevention and control, safety of the patient and healthcare worker,
      environmental concerns, and effective use of resources. From an infection
      prevention point of view, present requirements are based upon the intended use of
      the devices. Critical devices require sterilization. Semi-critical devices
      require, as a minimum, high level disinfection. Sterilization is, however,
      preferred whenever possible. Before sterilization or disinfection, devices should
      be cleaned adequately. Device designs should be readily amenable to cleaning and
      sterilization. In the past, design requirements focused primarily on the clinical
      user and device functionality, with reuse considerations left to the user. In the
      current market, the customer is redefined and, for reusable medical devices,
      includes all those associated with the device through the reprocessing procedure.
      In addition, regulations require that manufacturers give detailed instructions
      for reprocessing medical devices. The device users have the obligation to follow
      reprocessing instructions. Many choices exist today in device designs, including
      disposable or reusable devices. The user needs to balance cost versus convenience
      and reprocessing requirements for reusables. Current trends are to reuse more
      devices, including many of which were meant to be disposable. Cost effective
      designs can best be achieved when the user and manufacturer work together on the
      design.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7640418
TI  - Liquid chemical sterilization using peracetic acid. An alternative approach to
      endoscope processing.
AB  - Recurrent episodes of endoscope contamination with nontuberculous mycobacterium
      and Pseudomonas species, coupled with employee concerns about exposure to 2%
      glutaraldehyde and the requirement for rapid scope turnover time, led to the
      investigation of an alternative method for endoscope processing. A prospective
      evaluation of 220 bronchoscopy procedures was carried out. Endoscope culture
      surveillance was performed twice a month for a 12 month period on all endoscopes.
      In addition, the deliberate inoculation of bronchoscopes with Mycobacterium
      gordonae was carried out. No indications of cross contamination were noted among
      the 220 bronchoscopy procedures after processing the scopes by the studied liquid
      chemical sterilization system using peracetic acid. Ongoing patient surveillance
      did not reveal any indications of cross contamination for nearly 15,000 patients
      diagnostic or surgical endoscopic procedures using instruments processed by this
      liquid chemical sterilization system. Twice a month for 12 months, bronchoscopes,
      colonoscopes, and gastroscopes were cultured for bacterium, fungi, and acid fast
      bacilli and showed no growth. Deliberate inoculation of bronchoscopes with M.
      gordonae showed the scopes were rendered sterile. No unusual occurrences of
      occupational chemical exposure were found in 11 individuals working with this
      liquid chemical sterilization system. The peracetic acid based sterilization
      system studied proved to be an effective, safe, and economical alternative to the
      glutaraldehyde method.

PMID- 7640419
TI  - Automated liver cell processing facilitates large scale isolation and
      purification of porcine hepatocytes.
AB  - An automated method for large scale isolation and purification of porcine
      hepatocytes is described. Liver cells were harvested by a two-step portal vein
      perfusion with ethylenediaminetetraacetate and collagenase. Hepatocyte
      purification was carried out using either a standard manual processing method
      (Procedure A) or an automated processing method using a filtration chamber and a
      programmable cell washer (Procedure B). Both methods produced high cell yields
      (Procedure A: 1.30 +/- 0.55 x 10(10) viable hepatocytes/liver; Procedure B: 1.38
      +/- 0.32 x 10(10) viable hepatocytes/liver) and viability (Procedure A: 89 +/-
      6.5%; Procedure B: 92 +/- 3.9%). Hepatocyte purity was significantly greater
      after Procedure B than after Procedure A (93.1 +/- 3.1% versus 83.1 +/- 3%, p <
      0.01). Isolated hepatocytes by either method were morphologically intact, as
      demonstrated by transmission electron microscopy showing integrity of plasma
      membranes and intracellular organelles. Cultured hepatocytes isolated by either
      method were functionally intact, although those isolated by Procedure A showed
      significantly lower activity of microsomal 7-ethoxycoumarin-O-deethylase activity
      (p < 0.05) and mitochondrial succinate dehydrogenase activity (p < 0.01). In
      conclusion, use of the automated hepatocyte processing method resulted in
      efficient large scale preparation of porcine hepatocytes, with higher purity and
      greater retention of differentiated liver metabolic functions, and was found to
      be less time consuming and less labor intensive.

PMID- 7640420
TI  - Concepts in the application of pneumatic ventricular assist devices for ischemic
      myocardial injury.
AB  - The clinical results of "bridge-to-recovery" from ischemic myocardial injury
      using pneumatic ventricular assist devices (VADs) have been disappointing,
      because no significant improvement in the hospital discharge rate (25%) has been
      observed during the past 10 years. Interestingly, similar results have been
      reported using the less sophisticated and more widely available centrifugal
      pumps. It is well recognized that appropriate patient selection and early device
      implantation are important determinants of patient survival; however, it is less
      clear why there is a lack of difference in the results between pneumatic VADs and
      the centrifugal pumps. The reasons for the lack of difference in the results
      between pneumatic VADs and centrifugal pumps are multifactorial, and to some
      extent may be due to a conservative approach in the application of the more
      capable pneumatic VADs. In an effort to provide a more effective approach to the
      clinical application of pneumatic VADs for bridge-to-recovery, two pneumatic
      devices (the Jarvik 7-70 total artificial heart and the Symbion acute VAD) were
      functionally characterized using an in vitro mock circulatory system. The
      performance under pneumatic VAD asynchronous pumping compared to
      electrocardiogram synchronous counterpulsation was also evaluated. Based upon the
      results obtained, a two phase approach was developed. In the initial phase (i.e.,
      the first 12-48 hrs), device output is maximized through asynchronous pumping to
      rapidly reverse the effects of cardiogenic shock. During the second phase (i.e.,
      after hemodynamic stabilization and early evidence of end-organ recovery),
      electrocardiogram synchronous counterpulsation is used to focus more specifically
      on recovery of the heart.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7640421
TI  - Percutaneously inserted silastic jugular hemodialysis catheters seldom cause
      jugular vein thrombosis.
AB  - To find out whether internal jugular vein cannulation with a soft silastic
      hemodialysis access catheter causes jugular vein thrombosis, the authors carried
      out Doppler ultrasound examinations on 96 patients receiving hemodialysis who had
      undergone 144 separate catheter insertion episodes in 116 veins. Two internal
      jugular vein thromboses were found in 101 veins that had been the site of
      percutaneous insertions only. In addition, 5 internal jugular vein thromboses
      were identified in 15 veins that had been cannulated surgically with the Quinton
      PermCath. The authors conclude that percutaneous internal jugular vein
      cannulation for hemodialysis access causes an acceptably low incidence of jugular
      vein damage. This strengthens the case for preferential use of the internal
      jugular vein for vascular access in patients with end-stage renal failure, and
      suggests that percutaneous cannulation is less damaging than surgical insertion.

PMID- 7640422
TI  - Thromboxane B2 blood levels and incipient system clotting in heparin free
      hemodialysis.
AB  - Clotting of the extracorporal system is the main complication of heparin free
      hemodialysis performed in patients with an increased risk of bleeding. The
      authors compared thromboxane B2, platelet factor 4, beta-thromboglobulin, and
      thromboelastography in systemic blood as markers of thrombogenicity during
      hemodialysis in eight patients with an increased risk of bleeding. Measurements
      were performed during hemodialysis with and without heparin. Thromboxane B2
      levels in centrifuged blood were evaluated by an 125I assay system using a
      special extraction with mini-columns and magnetic separation (normal 32-64
      pg/ml). At the onset of hemodialysis, thromboxane B2 concentrations in the inflow
      arterial blood line were lower than normal (30 +/- 23 pg/ml). Thromboxane B2
      increased (97 +/- 105 versus 40 +/- 26 pg/ml) and was significantly higher during
      heparin free hemodialysis than during hemodialysis with heparin (p = 0.01,
      Wilcoxon matched pairs signed rank test). The highest values were observed in 5
      cases with signs of clotting (152 +/- 122 pg/ml). Among the investigated
      parameters, thromboxane B2 proved to be the most significant serum parameter
      correlated with platelet activation and the consequently increased risk of
      incipient clotting during heparin free hemodialysis.

PMID- 7640423
TI  - Excess mortality in small dialysis centers. The result of dialyzing high-risk
      patients.
AB  - End Stage Renal Disease Network 12 regularly collects information describing the
      Medicare dialysis population within its boundaries (Iowa, Nebraska, Missouri, and
      Kansas). Hoping to foster a regional quality improvement program, Network 12
      began calculating provider specific mortality rates in 1988. These rates were
      extremely variable, but small dialysis units (< or = 30 patients) generally had
      higher mortality rates than their larger counterparts. To determine why mortality
      rates were inversely proportional to the number of patients treated within the
      center, we undertook a more intensive statistical review of patient mortality
      rate within the network. Actual and expected mortality rates were derived for
      each Network 12 dialysis center. Forty-eight percent of dialysis centers served
      30 or fewer patients (small centers), and 40% had an expected mortality rate < or
      = 5 deaths per year. In 1989 and 1990, the crude mortality rate for dialysis
      centers enrolling 30 or fewer patients exceeded that of larger dialysis centers
      (p = 0.02). When Standardized Mortality Ratios were analyzed, this relationship
      disappeared (p = 0.83). Statistical review of dialysis providers is a complex
      process. Adjusting mortality rates for patient characteristics known to influence
      survival obviated the relation of dialysis unit size to patient mortality rate
      within Network 12. This suggests that patients were not randomly assigned to
      dialysis units and that small providers enrolled a disproportionate number of
      high risk patients. Adjusting mortality rates for endemic patient characteristics
      did not reduce the extreme variability noted in small mortality rates. This
      uncertainty, embedded in probability theory, cannot be eliminated from the
      statistical analysis of small samples.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7640424
TI  - Flow in a rotating membrane plasma separator.
AB  - Rotating filter separators are very effective in the separation of plasma from
      whole blood, but details of the flow field in the device have not been
      investigated. The flow in a commercial device has been modeled computationally
      using the finite element code FIDAP. Taylor vortices appear in the upstream end
      of the annulus but disappear in the downstream end because of increasing blood
      viscosity as plasma is removed. Fluid transport at the upstream end of the
      annulus results from both translation of Taylor vortices and fluid winding around
      the vortices. If the inertial effects of the axial flow are reduced, less fluid
      winds around the vortices and more fluid is transported by the translation of the
      vortices. The pressure at the membrane is nonuniform in the region where vortices
      appear, although the relative magnitude of the fluctuations is small.

PMID- 7640427
TI  - Cardiac pacing induced flow responses in internal thoracic artery and saphenous
      vein coronary artery bypass grafts.
AB  - The flow reactivity of an internal thoracic artery (ITA) graft and a vein graft
      for multiple coronary beds in response to different modes of cardiac pacing
      remains unclear. These experiments were conducted in 14 anesthetized dogs with
      the ITA or the vein grafted to the circumflex coronary artery, off pump, using a
      brief local occlusion. The left main coronary artery was occluded, rendering the
      entire left ventricle totally dependent upon the ITA graft or the vein graft.
      When the left main coronary artery was occluded and the heart rate was 120 beats
      per min, graft flow was 93.4 +/- 9.6 ml per min in the ITA, and 96.1 +/- 10.4 ml
      per min in the vein graft. Atrial pacing to increase heart rates 25% to 150 beats
      per min increased both the ITA graft flow (110.3 +/- 9.7 ml per min, p < 0.05
      versus flow in sinus rhythm) and the vein graft flow (109.8 +/- 7.9 ml per min, p
      < 0.05 versus flow in sinus rhythm). The increases in flow in both cases were not
      attributable to changes in perfusion pressure. In contrast, ventricular pacing to
      the same heart rate decreased systemic pressure slightly, but insignificantly.
      Despite the slight decrease in perfusion pressure, ventricular pacing increased
      ITA flow (107.9 +/- 8.4 ml per min, p < 0.05 versus flow in sinus rhythm), but
      the increase in vein graft flow was not significant compared with flow in sinus
      rhythm (102.1 +/- 7.3 ml per min, p = ns versus flow in sinus rhythm).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7640426
TI  - Leukocyte kinetics in patients with peritonitis on long-term peritoneal dialysis.
AB  - Dialysate and blood leukocyte counts were measured during 130 episodes of
      peritonitis in 91 hospitalized patients on long-term peritoneal dialysis (CPD).
      The authors found that the blood/dialysate leukocyte count can be less than 1.0,
      and this is usually the case when dialysate leukocyte count exceeds 20,000/mm3.
      Dialysate leukocyte removal in a single 2 L drain bag can approach the leukocyte
      number in the entire circulating blood volume. Daily drainage can remove
      leukocytes in amounts exceeding the blood leukocyte pool 2 to 3 fold. The
      observed blood leukocyte counts throughout a range of 2,700 to 10,000 at
      dialysate leukocyte counts greater than 20,000 per mm3 may reflect: 1) leukocyte
      removal approaching maximum bone marrow output of leukocytes, and/or 2)
      increasing microcirculatory margination of leukocytes in those episodes of
      peritonitis associated with very high dialysate leukocyte counts.

PMID- 7640425
TI  - Porcine hepatocytes from slaughterhouse organs. An unlimited resource for
      bioartificial liver devices.
AB  - Most recent strategies for the development of hybrid artificial liver devices
      focus on the use of parenchymal liver cells (hepatocytes). For clinical
      application of these devices, a sufficient cell supply is mandatory. Because
      human liver tissue is rarely available, isolated porcine hepatocytes from
      laboratory animals have been suggested for use in bioartificial livers. The
      authors introduce a modified isolation protocol to yield large scale numbers of
      viable porcine hepatocytes from slaughterhouse organs. Perfusion and enzymatic
      digestion of the left medial liver lobe (n = 74) resulted in 1.0 +/- 0.3 x 10(7)
      viable hepatocytes per gram of tissue, and an overall yield of 1.92 +/- 0.5 x
      10(9) viable cells per isolation (viability: 93 +/- 2%). Collagen gel
      immobilization maintained morphologic integrity and functional activity of
      hepatocyte cultures over long-term periods. Cell morphology, as assessed by light
      microscopic evaluation, was maintained for 2 weeks. Stable DNA content (51 +/- 5
      micrograms) and low values of alanine aminotransferase release (8
      microU/hr/micrograms DNA) indicated structural stability of cultures after a
      short period of post isolational adaptation. Albumin secretion (4.5
      micrograms/hr/micrograms DNA) and persistent Cytochrome P450 IA1 dependent
      deethylation of 7-ethoxycoumarin (4.5 nmol/hr/micrograms DNA) indicated long-term
      metabolic activity of cultured hepatocytes. Hepatocytes from livers of
      slaughtered pigs represent an unlimited resource of viable material for cell
      culture, and their usefulness as functional units of bioartificial liver support
      devices should be tested.

PMID- 7640428
TI  - Experimental evaluation of local reactions due to Dacron used in Tenckhoff
      catheters for peritoneal dialysis.
AB  - Inbred male Wistar rats were implanted subcutaneously with samples of Dacron and
      Silastic tubing as used in Tenckhoff catheters for peritoneal dialysis, to
      evaluate their capacity to evoke toxic reactions. Implants of Dacron induced a
      modest to severe granulomatous reaction with giant cell formation persisting for
      at least 30 days. Thereafter, this reaction subsided, with Dacron fibers being
      surrounded by fibrous sheaths. Silastic tubing induced a mild local reaction that
      regressed by day 10. Predictably, adverse reactions, including erosions,
      abscesses, and prolonged inflammatory changes noted in clinical patients
      implanted with Tenckhoff catheters may be attributable to misplacements of the
      catheters, recurrent infections, or toxic materials from extraneous sources, but
      not the materials used.

PMID- 7640430
TI  - Effects of different sampling methods for measurement of post dialysis blood urea
      nitrogen on urea kinetic modeling derived parameters in patients undergoing long
      term hemodialysis.
AB  - A simple and reliable sampling method for measuring post-dialysis blood urea
      nitrogen (C2) has not been well established. Therefore, the effects of different
      methods of sampling C2 on calculating urea kinetic modeling (UKM) derived
      parameters were studied in patients on hemodialysis. At first, C2 values were
      sampled at the end of hemodialysis at a blood flow rate of 300 ml per min (blood
      flow rate (Qb) 300 ml per min). They were then divided into two groups. In group
      1 (n = 11), C2 samples were taken after slowing down Qb to 100 ml per min for 3
      min (C2-100); the blood pump was then stopped for 1 min, and C2 was again sampled
      (C2-100-stop). Finally, C2 was sampled with Qb restored to 100 ml per min and the
      venous line clamped for another 12 sec (C2-100-clamp). In group 2 (n = 11), C2
      samples were collected after Qb was slowed down to 50 ml per min for 3 min (C2
      50), and C2-50-stop was then measured. Finally, C2-50-clamp was measured. Using
      C2-clamp as a reference standard, UKM parameters were calculated using a variable
      volume, single pool UKM. The authors found that Kt/V calculated by C2-300, C2
      100, and C2-50 overestimated the reference Kt/V by 8.4-9.1%, 5.1%, and 3%,
      respectively. In contrast, protein catabolic rate and time-averaged BUN were
      affected only minimally. Therefore, a low flow technique with a Qb of 50 ml per
      min for 3 min can be used for the routine estimation of C2 and UKM-derived
      parameters with reasonable accuracy.

PMID- 7640431
TI  - Biocompatibility and performance of a modified cellulosic and a synthetic high
      flux dialyzer. A randomized crossover comparison between cellulose triacetate and
      polysulphon.
AB  - The biocompatibility and performance of two high flux membranes (modified
      cellulosic: cellulose-triacetate (CTA), and a synthetic material: polysulphon
      [PS]) were assessed in 31 stable patients on hemodialysis (HD) in a randomized
      crossover study. Parameters evaluated included leukocytes, complement activation
      products C3a and C5a, cytokines, lymphocyte subpopulations, urea, creatinine,
      phosphate, and beta 2 microglobulin. Considering biocompatibility, the drop in
      the number of leukocytes was more pronounced during CTA HD compared with PS (p =
      0.045), although both were low in comparison with cuprammonium dialysis in the
      same patients, as observed during a separate study. Both membranes induced a low
      and transient state of complement activation. Interleukin 1 beta and interleukin
      6 could not be detected at all, whereas tumor necrosis factor alpha levels were
      marginally elevated before and after HD with both membranes. During the first 30
      min of HD with either membrane, the numbers of CD8+ cells decreased
      significantly, resulting in an increase in the CD4/CD8 ratios; in addition, the
      number of NK cells decreased. Performance, as measured by extraction ratios for
      small molecular weight solutes and Kt/V urea, was significantly better during CTA
      dialysis (p < 0.001), but almost similar after correction for membrane surface
      area. On the basis of these data, it seems justified to conclude that, whereas
      biocompatibility of the PS dialyzer appeared slightly superior to CTA,
      performance of both dialyzers was comparable.

PMID- 7640436
TI  - Does vacuum mixing of bone cement affect heat generation? Analysis of four cement
      brands.
AB  - Four different brands of bone cement (Palacos R, Simplex P, Sulfix, CMW 1) were
      tested for exothermic changes during polymerization at atmospheric pressure and
      under partial vacuum of 0.2 bar. Palacos R was also mixed at four pressure levels
      (1.0, 0.2, 0.12, and 0.05 bar). The peak temperature in the bone cement was 46 to
      124 degrees C, depending on the measuring point. There was no difference in peak
      temperature or duration of temperature increase above 50 degrees C during the
      curing of cement whether mixed at atmospheric pressure or under partial vacuum at
      different pressure levels.

PMID- 7640432
TI  - Zeolitic ammonium ion exchange for portable hemodialysis dialysate regeneration.
AB  - Ammonia removal from a recirculating dialysate stream is a major challenge in
      developing a truly portable, regenerable hemodialysis system. Three zeolites,
      type F, type W, and clinoptilolite, were found to have good ammonia ion exchange
      capacity with linear equilibrium ion exchange coefficients of 0.908, 0.488, and
      0.075 L/g, respectively. The linear equilibrium ion exchange coefficient relates
      dialysate ammonia concentration (mumol/L) to the amount of ammonia absorbed by
      zeolite (mumol/g) at equilibrium. Ammonia uptake by zeolite powders was fast,
      with equilibrium reached within 15 sec. Zeolite ammonia ion exchange and
      regeneration through multiple cycles was studied using an ion exchange column
      containing clinoptilolite pellets. Zeolite ion exchange capability was
      regenerated by flushing the column with 2 mol/L sodium chloride after an ion
      exchange run. The column maintained ammonia ion exchange capacity through six ion
      exchange/regeneration cycles, demonstrating multiple dialysis use possibilities.
      Atomic absorption spectroscopy of the column effluent showed no detectible (< 1
      part per million) Si or Al leached from the zeolite.

PMID- 7640434
TI  - New and prevalent patients with end-stage renal disease in Canada. A portrait of
      the year 2000.
AB  - The number of patients initiating treatment for end-stage renal disease (ESRD)
      has increased dramatically in Canada and other countries. To assist healthcare
      planners, the prevalence of ESRD in Canada has been projected to the year 2000
      using a Markov modelling technique. Significant increases in ESRD are expected in
      Canada during the next decade, particularly among the elderly and diabetic
      populations: estimated increases in prevalence rates of ESRD between 1992 and the
      year 2000 were 78% and 154% for non diabetic and diabetic populations
      respectively. These expected increases did not differ significantly between the
      treatment groups, except among patients with diabetes, in whom projected
      increases in the prevalence of functioning transplant was smaller than for
      hemodialysis or peritoneal dialysis. Because the current Canadian prevalence
      rates are lower than those of some other countries, such as the United States and
      Japan, these expected trends in prevalence appear reasonable, and illustrate the
      growing healthcare needs of the ESRD population in Canada during the next decade.

PMID- 7640429
TI  - Skeletal muscle ventricles seeded with autogenous endothelium.
AB  - Skeletal muscle ventricles (SMVs) are muscular pumping chambers constructed from
      skeletal muscle. Previously, SMVs were connected to the systemic circulation with
      vascular conduits and used to assist the heart. In this study, SMVs were
      constructed from the latissimus dorsi muscle in eight dogs. The SMVs were seeded
      with autologous endothelial cells, but not connected to the circulation.
      Endothelial cells were harvested enzymatically from autogenous external jugular
      vein and grown in tissue culture. After 9 weeks, 6 electrically conditioned SMVs
      were seeded with endothelial cells by injecting 4-5 ml of culture medium
      containing 5-8 x 10(6) autogenous endothelial cells into each SMV lumen adjacent
      to the mandrel. Conditioning was stopped at the time of endothelial seeding. One
      week after seeding, electrical conditioning was resumed. Two weeks after seeding,
      the animals were killed and the SMVs excised. Histologic examination confirmed
      the presence of a confluent monolayer of cells covering 80-100% of the luminal
      surface in each seeded SMV. The endothelial nature of the cells lining the SMV
      lumen was established by fluorescent microscopy. Endothelial cells were pre
      labeled with the cellular marker PKH before seeding; the SMVs were also incubated
      with the endothelial marker dil-acetylated LDL. Endothelial cells also were
      identified by staining with fluorescently labeled antibodies to von Willebrand
      factor. Based upon these data, electrically conditioned SMVs can be seeded
      successfully with a near-complete, autologous endothelial monolayer.
      Additionally, this endothelial monolayer can be maintained on the luminal surface
      of a contracting SMV. In-circulation studies will determine whether endothelial
      cell seeding of SMVs can decrease or eliminate the incidence of thromboembolism.

PMID- 7640435
TI  - A fibrin clot stops low density lipoprotein apheresis.

PMID- 7640437
TI  - Acute toxicity of metal ions in cultures of osteogenic cells derived from bone
      marrow stromal cells.
AB  - The effects of metal ions released from orthopedic implants on nearby bone cells
      remain largely unknown. The purpose of this study was to examine the acute
      toxicity of metal ions on osteogenic cells derived from bone marrow. Bone marrow
      stromal cells were cultured with metal ions found in commonly used orthopedic
      implants, that is, Ti-6Al-4V, Co-Cr-Mo, and 316L stainless steel. Solutions of
      individual ions and combinations representing the alloy composition were prepared
      from atomic absorption standards and added to the cultures to give concentrations
      ranging from 50 ppb to 50 ppm. After a 48-h period of exposure to ions, the bone
      marrow cultures were examined for effects of cytotoxicity by measuring total cell
      number, total cell protein, and mitochondrial activity. Cr6+ was grossly
      cytotoxic; Co2+, Mo6+, Fe3+, and Ni2+ were moderately cytotoxic; and Ti4+, Al3+,
      V5+, and Mn2+ were minimally toxic, as determined by the assays used. Ion
      solutions representing Co-Cr-Mo and 316L stainless steel were moderately toxic;
      solutions representing Ti-6Al-4V were toxic at only the highest concentrations
      used. The observed cytotoxicity was time-dependent, with irreversible toxic
      effects being initiated following as short as a 3- to 6-hour exposure. These
      results show that metal ions associated with Co-Cr-Mo and 316L stainless steel
      are toxic to osteogenic cells at concentrations approximating those measured in
      the fibrous membrane encapsulating orthopedic implants.

PMID- 7640440
TI  - Preliminary effects of in vitro lipid exposure on absorbable poly(ortho ester)
      films.
AB  - Bioabsorbable films show promise in preventing postoperative interfacial tissue
      adhesion. Absorbable polymers in film form are generally more sensitive to
      chemical environments, due to their large surface area to volume ratio. The in
      vivo environment contains lipids such as cholesterol, triglycerides, and
      phospholipids, which are known to affect the degradation of permanent and
      absorbable polymeric biomaterials. Preliminary investigations of in vitro lipid
      exposure of bioabsorbable poly(ortho ester) (POE) films for implant use are
      described. POE has been studied previously for use in controlled drug delivery
      and fracture fixation. Six-week in vitro exposure of 65:35 POE films to a
      cholesterol emulsion (1 g/L) showed no apparent difference in hydrolytic
      degradation rates of mechanical properties or mass loss compared to deionized
      water exposed films. Decreases of 28 and 6% in inherent viscosity were observed
      after 5 weeks for cholesterol and deionized water exposed films, respectively,
      suggesting cholesterol may have some effect. Further examination of the data, due
      to sample variation, revealed that clear, uniform films showed only minor changes
      in mass loss and mechanical properties after 6 weeks in either of the in vitro
      media. But slightly cloudy films possessing microscopic bubbles showed
      accelerated degradation in both media, indicating the effect of cholesterol was
      inconclusive due to sample variation. Control of the microbubble formation
      process could have utility in controlling hydrolytic degradation of POE films.

PMID- 7640438
TI  - Materials and design concepts for an intervertebral disc spacer. II.
      Multidurometer composite design.
AB  - The main function of the intervertebral disc is to transmit and attenuate
      compressive and torsional forces, and stabilize the intervertebral joint.
      Unfortunately, the disc may be displaced or damaged due to trauma or disease
      causing the nucleus to herniate and protrude into the vertebral canal or
      intervertebral foramen. Pressure on the spinal nerve may cause pain or paralysis
      in the area of its distribution. At present, the surgical procedures used to
      alleviate this condition include disc excision, and/or spinal fusion. A more
      desirable situation would involve removing the nucleus pulposus and part or all
      of the annulus fibrosis and implanting a suitable biofunctional equivalent. Such
      a prosthesis should attenuate stresses and prevent abnormal stress at adjacent
      intervertebral joints. Maintenance of normal disc height would prevent
      impingement of the posterior facet joints and facet joint syndrome. In a previous
      companion paper (J. Applied Biomat. 5:125-132; 1994), the mechanical behavior of
      disc prostheses manufactured from fiber reinforced, elastomeric thermoset resins
      were examined. In order to develop devices which were more practical from a
      manufacturing standpoint and extremely reproducible, the fiber reinforced
      thermoset resins were replaced by multi-durometer thermoplastic elastomeric
      materials. In the present paper, the mechanical properties of thermoplastic
      multicomponent designs have been investigated.

PMID- 7640441
TI  - Educational goals for biomaterials science and engineering: prospective view.
AB  - The research field of biomaterials and surgical implants has matured to a point
      suggesting that a formal and comprehensive education is now required to handle
      all professional issues related to biomaterials and implant development. A
      professional curriculum is proposed for a discipline of biomaterials science and
      engineering on a graduate level. The curriculum includes the definition of an
      essential knowledge base and describes two track options for a study period of 3
      years. Lists of prerequisites as well as required and suggested courses are
      presented and discussed. Continuing education courses are presented as examples.
      A quick vision of the immediate future of the field enforces the need for
      biomaterials professionals to take the lead in bringing the field into the next
      century.

PMID- 7640439
TI  - Characterization of three formulations of a synthetic foam as models for a range
      of human cancellous bone types.
AB  - Porous polyurethane foams were prepared from Daro foam components with a range of
      mechanical properties to simulate human trabecular bone. Ratios of 10.0:5.0,
      10.0:7.9, and 10.0:10.0 isocyanate to resin were mixed, cured, and cut into
      cubes. Properties were determined from uniaxial compression to 50% of the
      original cube height at a strain rate of 1.2 mm/s. Electron microscopy was used
      to characterize the foam structure. Average compressive yield stress values,
      ultimate compressive stresses, and elastic moduli ranged from 4.44 to 2.79, 5.61
      to 3.28, and 134.0 to 110.1 MPa, respectively, for the three formulations. The
      foam materials showed a similar morphology of spherical bubbles, and the average
      bubble size tended to decrease as the ratio of isocyanate to resin increased even
      though the bubble size differences were not statistically significant. The
      results indicate that large blocks of foam can be prepared with consistent
      mechanical properties simulating a range of trabecular bone properties so that
      implants can be tested for various patient populations.

PMID- 7640442
TI  - Technical note: bioluminescent bacterial test for acute toxicity: the effect of
      pH and buffer solutions.

PMID- 7640443
TI  - The editor's corner: medical technology and competitiveness in the world market:
      reinventing the environment for innovation.

PMID- 7640433
TI  - Short phase efficacy of autologous peritoneum as a pericardial substitute.
AB  - The risks associated with resternotomy are largely related to loss of pericardial
      integrity. No satisfactory substitute for pericardium has been identified. The
      structural similarity between pericardium and peritoneum prompted an assessment
      of the latter as a biologic substitute. Two peritoneal patches were harvested
      from four juvenile swine, which then underwent left thoracotomies. In each pig,
      two pericardial defects were created and repaired with fresh and glutaraldehyde
      treated autologous peritoneal patches. Three weeks post operatively, the chest
      and abdomen were re-explored and the patches evaluated. In all cases,
      extrapericardial adhesions were insignificant. On gross examination of the
      intrapericardial surfaces, the fresh patches appeared smooth and glistening, with
      neither degenerative changes nor adherence to the epicardium. The treated patches
      were easily separated from the epicardium in two cases, but the other two patches
      were moderately to severely adherent. Histologic examination demonstrated well
      preserved morphology in all patches. C proline uptake and autoradiography
      revealed preserved fibroblast viability in the fresh patches. Intra abdominally,
      in all cases, there was complete reperitonealization without adhesion formation.
      In conclusion, fresh autologous peritoneum performed well as a pericardial
      substitute after heart surgery.

PMID- 7640444
TI  - Histological and electron microscopic analysis of tissue response to synthetic
      composite bone graft in the canine.
AB  - A synthetic composite bone graft material, composed of fibrillar collagen,
      hydroxyapatite, and tricalcium phosphate, was evaluated in canine femoral shaft
      defects and compared to ungrafted defects and defects grafted with autogenous
      bone. The results of mechanical testing of the grafted femora in torsion at 1
      year postoperatively were previously reported. This report details the
      histological and microscopic features of the graft sites. The results of this
      study suggest that the healing of the graft site is not yet complete at 1 year
      and that healing may be more complete in defects that received the synthetic
      graft as compared to ungrafted sites and autogenous bone graft. The bone tissue
      appears to respond to the graft particles as if they were bone particles.

PMID- 7640446
TI  - Report on the first annual survey of home parenteral nutrition in Japan.
AB  - An annual survey of the current national status of home parenteral nutrition
      (HPN) in Japan was begun in 1991, with a total of 231 registered patients from
      142 institutions providing adequate data for evaluation and analysis. HPN was
      given for an average of 683 +/- 764 days to 93 patients with malignant diseases
      and 138 with benign disease, including 53 with inflammatory bowel disease and 79
      with short bowel syndrome, 107 (46.3%) of whom were successfully rehabilitated.
      By the end of 1990, 61% of the patients investigated were still on HPN, 7% had
      already completed HPN, and 26% had died, the deceased accounting for 54% of the
      patients with malignant diseases and 7% of those with benign diseases. A total of
      321 catheters had been used by all 231 patients, the most common being the
      subcutaneously implanted type, accounting for 33% of all catheters. By the end of
      1990, 32% of these 321 catheters were still in place, 18% had been removed on the
      termination of HPN and 44% had been removed due to complications of total
      parenteral nutrition, including 20% for catheter fever. Rehospitalization was
      required in 62% of the patients, the cause being HPN-related in 21% of the total
      patients. Metabolic complications were experienced by 60% of the patients, but
      none of these were severe although 6% required hospitalization.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7640445
TI  - Increase of stability in external fracture fixation by hydroxyapatite-coated bone
      screws.
AB  - A major problem in fracture treatment by external fixation is screw loosening,
      which often results in reduced stability and can lead to prolonged treatment. A
      load-carrying experiment was conducted to determine whether coating implants with
      bioactive hydroxyapatite (HA) increases screw stability. Twelve HA-coated ASIF
      screws with 3 different macroporosities were inserted in 12 sheep that had
      already been fitted with a 6-pin external fixator for the treatment of a tibial
      osteotomy. The same number of uncoated polished steel screws served as controls.
      Although initial stability was not different for HA-coated screws, average
      removal torque after a 9-week implantation period increased with increasing
      macroporosity of the HA coating (p < .002). Instability of some screws was
      accompanied by histologic findings of cartilagenous tissue and proliferation of
      periosteal callus. Near the threads in the tibial cortex and in the shaft area of
      the screw were seen large numbers of HA particles that had been sheared off
      during implantation as well as during screw removal because of high contact
      forces between the HA coating and bone. Particulate debris of HA particles as
      well as the release of small bone fragments during explanation is likely to be
      unavoidable since HA adherence to bone is greater than adherence to steel after
      several weeks of implantation.

PMID- 7640448
TI  - Prophylactic portal infusion chemotherapy as adjuvant therapy for the prevention
      of metachronous liver metastasis in colorectal cancer.
AB  - The DNA ploidy and DNA indices (DI) of 414 patients with colorectal cancer were
      analyzed, and the incidence of patients with metachronous liver metastasis was
      found to be significantly higher in those with aneuploid tumors and a DI above
      1.5 than in those with aneuploid tumors and a DI below 1.4, or in those with
      diploid tumors and a DI equal to 1.0. Next, to confirm the effectiveness of
      administering prophylactic portal infusion chemotherapy (PPIC) as adjuvant
      therapy for the prevention of metachronous liver metastasis in colorectal cancer,
      a randomized controlled trial of PPIC was performed on 110 consecutive patients
      with primary colorectal cancer who had undergone curative resection. Although the
      incidence of patients with metachronous liver metastasis in the two study groups
      was not significantly different at 3.3% in the PPIC group and 10.3% in the
      control group, the incidence in the patients with aneuploidy and a DI above 1.5
      was significantly lower in the PPIC group than in the control group. These
      findings suggest that colorectal cancer with aneuploidy and a DI above 1.5 may
      have a strong tendency to metastasize to the liver, and that prophylactic portal
      infusion chemotherapy may be effective for preventing metachronous liver
      metastasis in such patients.

PMID- 7640447
TI  - Peritoneal lavage versus drainage for perforated appendicitis in children.
AB  - A total of 231 children with acute appendicitis were treated at our hospitals
      during the 10 years between 1984 and 1993, 53 of whom had a perforated appendix.
      These 53 patients were randomly assigned to two groups at the time of surgery
      according to the different procedures performed. Thus, 29 children were managed
      by appendectomy followed by peritoneal lavage using a large amount of saline, and
      intravenous antibiotic therapy consisting of aminoglycoside and cephem (lavage
      group), while the other 24 children were treated by appendectomy with silicon
      tube drainage and the same systemic antibiotic therapy (drainage group). The mean
      length of hospitalization, and the mean durations of fever and the need for
      fasting after laparotomy in the lavage group were significantly less than those
      in the drainage group: 10.1 versus 18.8 days, 2.8 versus 7.7 days, and 1.8 versus
      3.5 days, respectively. The operation wounds healed well in the lavage group due
      to the fact that there was no drain. Wound infections occurred in two children
      from the lavage group and six from the drainage group. Intra-abdominal abscesses
      occurred in two children from the drainage group. Accordingly, peritoneal lavage
      appears to be superior to intraperitoneal tube drainage for the management of
      perforated appendicitis in children.

PMID- 7640450
TI  - Changes in serum myosin light chain I following aortocoronary bypass operations.
AB  - The changes in myosin light chain I (MLC I) following aortocoronary bypass were
      studied in 31 patients and the curves of these changes were classified into three
      different patterns. A peak level of 14.7 +/- 1.54 ng/ml was seen in seven
      patients on postoperative day (POD) 2 which decreased suddenly to less than twice
      the normal value by POD 7 (group 1). Another 19 patients showed a peak level of
      20.7 +/- 16.5 ng/ml on POD 5, which decreased slowly and was still high even by
      POD 7 (group 2). The remaining five patients developed only a slight increase in
      the MLC I level after the operation, with a peak value of 5.5 +/- 0.8 ng/ml
      (group 3). Creatine kinase myocardial band and glutamic oxaloacetic transaminase
      also remained low in this group. No correlation existed between the peak value of
      MLC I and the aortic cross-clamping time, or between the peak value of MLC I and
      the cardiopulmonary bypass time. Furthermore, the difference in cardiac output
      before and after the operation did not significantly differ among the three
      groups. These findings indicate that the measurement of MLC I is useful for
      diagnosing perioperative myocardial damage and may also be useful in the study of
      myocardial protection.

PMID- 7640451
TI  - Mid-term surgical results after valve replacement with the CarboMedics valve
      prosthesis.
AB  - We present herein a review of 95 patients who underwent valve replacement with
      the CarboMedics (CM) valve prosthesis between April 1990 and December 1992. The
      operative mortality for the entire group was 4.2%: 0% following aortic valve
      replacement (AVR), 2.7% following double valve replacement (DVR). All patients
      were prescribed warfarin and bucolome for anticoagulation, and were followed up
      for a mean period of 29.9 months. Late mortality was 8.4%; 3.1% following AVR,
      10.8% following MVR, and 12.5% following DVR. There were no cases of mechanical
      prosthetic valve failure, significant hemolysis, infective prosthetic valve
      endocarditis, or bleeding complications. After 44 months of follow-up, the
      actuarial freedom from complications was calculated as: thromboembolism, 97.8 +/-
      1.6%; valve thrombosis, 97.8 +/- 1.1%; paravalvular leak, 96.7 +/- 1.9%; and
      reoperation, 98.9 +/- 1.1%. The overall survival rate was 84.3 +/- 6.3% and all
      survivors showed a significant improvement in NYHA functional class, from 81% in
      classes III and IV preoperatively to 99% in classes I and II postoperatively. The
      CM valve exhibited no significant differences in hemolytic parameters or
      hemodynamic performance after isolated AVR or MVR compared with the similar type
      of St. Jude Medical bileaflet valve. The evidence provided by the present study
      therefore suggests that the CM valve prosthesis can achieve excellent mid-term
      clinical results and hemodynamic performance with a low incidence of
      thromboembolism and valve thrombosis.

PMID- 7640449
TI  - Clinicopathological findings and p53 expression of thyroid cancer in children.
AB  - Although thyroid cancer tends to metastasize early in children, it is generally
      associated with a good prognosis. In this study, the expression of p53, mutations
      of which are found in many cancers, including anaplastic thyroid cancer, was
      examined to determine the relationship between cell proliferation and the
      clinical course of thyroid cancer. The clinicopathological findings and clinical
      courses of 15 children who underwent surgery before the age of 18 years at our
      hospital between 1972 and 1992 were examined, and the expression of p53 was
      studied using immunohistochemical techniques and an RNase protection assay.
      Postoperative follow-up ranged from 1 to 20 years, with a median of 12 years. No
      abnormal expression of p53 was detected in the thyroid cancer of any of the
      children tested, and none of them have died. The findings of this study therefore
      strongly suggest that p53 may play a role in the regulation of cell
      proliferation, and in this capacity slow the growth of and be related to the
      prognosis of differentiated thyroid cancer in children.

PMID- 7640452
TI  - Conversion of the rabbit gracilis muscle for transposition as a neoanal sphincter
      by electrical stimulation.
AB  - To re-establish anal function in fecally incontinent patients it may be feasible
      to transpose the gracilis muscle around the anal canal, using electrical
      stimulation to trigger contraction. However, because the fast-twitching gracilis
      muscle is incapable of prolonged contraction without fatigue, it is necessary to
      convert it to a slow-twitching, fatigue-resistant muscle. We demonstrated this
      conversion by longterm electrical stimulation at low frequencies using a rabbit
      model. The nerve to the gracilis muscle was continuously stimulated at 2 Hz, 5
      Hz, and 10 Hz for 2, 4, or 6 weeks. In the 6-week conditioning group, the
      percentage of type I fibers, identified by ATPase staining, increased as the
      conditioning frequency became higher, but the twitch contraction speed reduced
      with conditioning at a frequency of more than 5 Hz. The fatigue resistance
      improved by conditioning at 10 Hz, and conversion occurred in 6 weeks. Thus, we
      concluded that conditioning at 10 Hz for 6 weeks can convert rabbit gracilis
      muscle to a slow-twitching, fatigue-resistant muscle suitable for use as a
      neoanal sphincter.

PMID- 7640454
TI  - Characterization of cell surface antigens expressed in the HMA-1 breast cancer
      cell line.
AB  - This report describes the characterization of an estrogen receptor-positive
      breast cancer cell line, HMA-1, established from a breast cancer patient, based
      on the expression of tumor-associated antigens (TAAs), the HLA-DR antigen, and
      the c-erbB-2 proto-oncogene product. In flow cytometric and immunohistochemical
      analyses, HMA-1 was found to express increased levels of several TAAs including
      MUC1, TAG-72 (sialyl Tn), Tn, T, sialyl Le(a), Le(x), and Le(y). HMA-1 also
      expressed enhanced levels of the HLA-DR antigen and c-erbB-2 protein. These
      results indicate that HMA-1 is a unique cell line with abundant TAAs which may
      serve as an appropriate breast cancer cell line for application in the
      multidisciplinary research of breast cancer.

PMID- 7640453
TI  - Expression of HGF and TGF-beta 1 mRNA after partial hepatectomy in rats with
      liver cirrhosis.
AB  - Hepatocyte growth factor (HGF) is a potent mitogen for the maturation of
      hepatocytes in vitro which plays a role in liver regeneration in vivo. In
      addition, transforming growth factor-beta 1 (TGF-beta 1) is also a potent
      regulator of liver regeneration. In attempting to clarify the mechanisms related
      to liver regeneration after partial hepatectomy, we investigated the expression
      of HGF and TGF-beta 1 in rats with liver cirrhosis (LC). A rat model of LC was
      prepared using carbon tetrachloride (CCl4). The expression of HGF mRNA in both
      the LC and control groups showed a similar time-course with the highest
      expression seen at 18h after a 70% hepatectomy. The expression of TGF-beta 1 mRNA
      peaked at 18h after partial hepatectomy in the LC group and at 48h in the control
      group. The 5-bromo-2'-deoxyuridine (BrdU) labeling index for the LC group at 24,
      48, and 72 h after partial hepatectomy was 9.2%, 5.9%, and 1.8%, while for the
      control group it was 7.0%, 11.7%, and 6.8%, respectively. The BrdU labeling index
      in the LC group was thus suppressed earlier than that in the control group. We
      therefore postulate that regeneration of the remnant liver in the presence of LC
      accelerates immediately after partial hepatectomy, but the extent of regeneration
      is insufficient because of an early cessation due to an early expression of TGF
      beta 1.

PMID- 7640456
TI  - Carcinoma of the reconstructed stomach tube following esophageal resection for a
      benign stricture: report of a case and review of the literature.
AB  - We report herein the case of a 60-year-old woman who presented with dysphagia and
      anorexia and was subsequently diagnosed as having gastric cancer of the
      reconstructed stomach tube 36 years after undergoing surgery for a benign
      esophageal stricture. Reports on carcinoma of the reconstructed stomach tube are
      rarely found and interestingly, all of the previous cases, which were documented
      only in the Japanese literature, corresponded to metachronous double cancers
      after esophageal malignancies. To our knowledge, this is the first case of
      carcinoma of the reconstructed stomach tube following esophageal resection for a
      benign stricture, and it is thought that the carcinoma probably developed at the
      site of the anastomosis a long time after the first operation. We reviewed 30
      cases of carcinoma of the reconstructed stomach tube for which the
      clinicopathological data was complete, and we believe that this new type of
      cancer needs more than 10 years to develop and should be defined as "carcinoma of
      the gastric remnant".

PMID- 7640455
TI  - Long-term hypothermic preservation of cardiac myocytes isolated from the neonatal
      rat ventricle: a comparison of various crystalloid solutions.
AB  - In this study, the functional and biochemical effects of crystalloid solutions on
      immature cardiac myocytes incubated under hypothermic conditions were evaluated.
      Cardiac myocytes were isolated from neonatal rat ventricles and cultured for 4
      days, following which 12.5 x 10(5) myocytes per flask were incubated at 4 degrees
      C for 3, 6, 12, and 18 h in five types of crystalloid solutions: lactated
      Ringer's (LR), St. Thomas' Hospital (ST), University of Wisconsin (UW), 5%
      glucose-based potassium (GK), and normal saline (NS). The levels of creatine
      phosphokinase (CPK) and lactate dehydrogenase (LDH) in the solutions were
      measured after each hypothermic incubation, following which the myocytes were
      cultured for an additional 24 h at 37 degrees C to evaluate the recovery of the
      myocyte beating rate. In the LR, UW, and NS groups, the recovery ratios of the
      myocyte beating rate were over 95% of the control (the beating rate prior to
      hypothermic incubation) at 3 h, but decreased to 20.3, 15.1, and 0%,
      respectively, at 18 h. The ST and GK groups had significantly lower recovery
      ratios than the other three groups (72.9% and 63.4%, respectively) at 3 h. The
      release of CPK and LDH in the LR, UW, and NS groups was significantly suppressed
      compared to the ST and GK groups, with the greatest suppression observed in the
      LR group. Moreover, the ST and GK groups had the highest CPK and LDH levels,
      respectively. Thus, LR solution had the least cytotoxic effects, indicating that
      it could be the most suitable basic solution of the various cardioplegic or
      preservation solutions during the neonatal period.

PMID- 7640458
TI  - Conservative management of idiopathic pneumoperitoneum masquerading as
      peritonitis: report of a case.
AB  - Pneumoperitoneum is most commonly caused by the perforation of a hollow viscus,
      in which case an emergency laparotomy is indicated. We report herein the case of
      a patient who presented with the signs and symptoms of peritonitis, but who was
      found to have idiopathic pneumoperitoneum which was successfully managed by
      conservative treatment. A 70-year-old man presented with epigastric pain, nausea,
      and a severely distended and tympanitic abdomen. Abdominal examination revealed
      diffuse tenderness with guarding, but no rebound tenderness. He was febrile with
      leukocytosis and high C-reactive protein. Chest X-ray and abdominal computed
      tomography demonstrated a massive pneumoperitoneum without pneumothorax,
      pneumomediastinum, pneumoretroperitoneum, or subcutaneous emphysema, and
      subsequent examinations failed to demonstrate perforation of a hollow viscus.
      Thus, a diagnosis of idiopathic pneumoperitoneum was made, and the patient was
      managed conservatively, which resulted in a successful outcome. This experience
      and a review of the literature suggest that idiopathic pneumoperitoneum is
      amenable to conservative management, even when the signs and symptoms of
      peritonitis are present.

PMID- 7640459
TI  - The successful repair of annuloaortic ectasia using Cabrol's operation in a 5
      year-old child with Marfan's syndrome of the forme fruste type.
AB  - This report describes our experience of treating a 5-year-old boy with
      annuloaortic ectasia and a presumptive diagnosis of Marfan's syndrome. He had
      elongation of the distal aortic arch and dilatation of the abdominal aorta.
      Surgical repair of annuloaortic ectasia was successfully carried out using
      Cabrol's operation, following which no significant perioperative complications
      developed. To our knowledge, this is the first reported case of Cabrol's
      operation being successfully performed on a child aged 5 years or less.

PMID- 7640460
TI  - Klippel-Trenaunay syndrome associated with splenomegaly: report of a case.
AB  - We report herein the case of a 19-year-old woman, diagnosed as having Klippel
      Trenaunay syndrome at the age of 3 years, who presented to our hospital with
      severe abdominal pain. Abdominal computed tomography revealed splenomegaly,
      ascites, and paracentesis confirming an intraabdominal hemorrhage. Thus, an
      emergency laparatomy was performed for a suspected splenic rupture, and 2.5 L of
      blood was drained from the abdominal cavity. Splenomegaly was confirmed, and a
      splenectomy was performed. The patient's postoperative course was complicated by
      disseminated intravascular coagulation, but she recovered and was discharged 3
      weeks following surgery. Pathological examination of the spleen suggested that
      the splenomegaly was caused by high venous pressure due to splenic vein stenosis.
      To our knowledge, this is the first reported case of Klippel-Trenaunay syndrome
      associated with marked splenomegaly.

PMID- 7640462
TI  - Right pneumonectomy syndrome: report of two cases.
AB  - We report herein the cases of two infants who developed right pneumonectomy
      syndrome, both of whom were born with gross C-type esophageal atresia (EA/TEF),
      and a hypoplastic right lung arising from the lower esophagus, being a
      bronchopulmonary foregut malformation (BPFM). Appropriate and well-timed
      treatments for a variety of sequelae primarily caused by the mediastinal shift
      must be considered after right pneumonectomy in early childhood.

PMID- 7640461
TI  - A new approach for performing a one-stage operation through the mediastinum to
      resect bilateral lung metastases: report of a case.
AB  - We describe herein a new operative technique for reaching the opposite lung from
      the thoracotomy site through the mediastinum. This procedure was successfully
      performed on a 76-year-old woman with bilateral lung metastases whose case is
      presented. After resection of the right lower lobe which contained two
      metastases, the anterior mediastinum was opened, and contralateral metastasis
      located in the lingular segment was resected using a neodymium:yttrium-aluminum
      garnet (Nd:YAG) laser. A chest drainage tube was inserted through the mediastinal
      window. This transmediastinal approach seems to be a feasible technique for
      preserving the respiratory function of the chest wall in patients with imbalanced
      bilateral metastases.

PMID- 7640457
TI  - Application of whole-body positron emission tomography in the imaging of
      esophageal cancer: report of a case.
AB  - We describe herein a case of esophageal cancer in which both primary and
      metastatic lymph node foci were successfully imaged with whole-body positron
      emission tomography (PET) scanning. A 75-year-old woman with biopsy-proven
      squamous cell carcinoma of the esophagus underwent whole-body PET scanning for
      staging evaluation. The patient was injected with 373.7 MBq [18F]-2-fluoro-2-D
      deoxyglucose (FDG), and 60 min later, scanning was performed from the neck to the
      pelvis. The whole-body images showed intense FDG uptake in the primary lesion and
      multiple focal areas of increased FDG uptake in the mediastinum and abdomen,
      which corresponded to the lymph node foci confirmed by computed tomography (CT)
      scan. To our knowledge, this is the first report of whole-body PET scanning being
      applied in the imaging of esophageal cancer.

PMID- 7640463
TI  - Gene rearrangement studies on lymphoma of the lung: report of a case.
AB  - We describe herein how true lymphoma of the lung was differentiated from
      pseudolymphoma in a 45-year-old woman presenting with pulmonary infiltrates.
      Although segmental resection revealed typical histologic findings of
      pseudolymphoma of the lung and immunohistochemical studies did not demonstrate a
      monoclonal proliferation, Southern blot analysis of the frozen tissue revealed
      rearrangements in the heavy and light chains of the immunoglobulin gene, with no
      T-cell receptor gene rearrangement suggestive of a lymphoproliferative disorder.
      These findings indicate that the identification of gene rearrangement may be
      utilized to distinguish between true lymphoma and pseudolymphoma.

PMID- 7640464
TI  - Successful one-stage operation for completely obstructive colorectal carcinoma.
AB  - We describe herein a new and successful method of performing a safe and steady
      one-stage operation for completely obstructive colorectal carcinoma. First, a
      long ileus tube is utilized to decompress the dilated proximal bowel
      preoperatively and irrigate the feces-loaded colon intraoperatively. Following
      this procedure, a standard resection with radical lymph node dissection is
      carried out without a diverting colostomy. We performed this procedure
      successfully in seven patients, none of whom developed any anastomotic leakage.

PMID- 7640465
TI  - PCNA immunostaining combined with AgNOR staining in esophageal squamous cell
      carcinoma to identify patients with a poor prognosis.
AB  - Immunostaining of the proliferating cell nuclear antigen (PCNA) provides
      important information about cell kinetics and is easily performed on routinely
      obtained formalin-fixed, paraffin-embedded materials. We report herein the
      results of a retrospective study on PCNA staining in esophageal cancer undertaken
      to determine its significance. As this study indicated that immunoreactivity was
      preserved in specimens fixed within 24h, only 31 specimens from surgical patients
      were available for this investigation. The mean PCNA index of the patients
      without invasion to the adventitia (35.7 +/- 17.9) was significantly lower than
      that of those with invasion to the adventitia or neighboring structures (49.7 +/-
      14.5), while the PCNA index did not correlate with other clinicopathologic
      parameters such as histologic type, lymph node metastases, or prognosis. However,
      when an analysis of PCNA staining was combined with an analysis of argyrophilic
      nucleolar organizer region (AgNOR) staining, a correlation with prognosis was
      found. In fact, seven patients with a high PCNA index (> or = 44) and AgNOR count
      (> or = 6) had a significantly poorer prognosis than the remaining 22 (P =
      0.0014), and six of these seven patients died within 2 years. These results
      indicate that this combined evaluation may be useful for the identification of
      patients with a poor prognosis among those undergoing surgery for esophageal
      squamous cell carcinoma.

PMID- 7640466
TI  - Preoperative intraperitoneal chemotherapy for gastric cancer, with special
      reference to delayed peritoneal complications.
AB  - Preoperative intraperitoneal (IP) chemotherapy was performed in 23 patients with
      gastric malignancies to inhibit peritoneal recurrence. Cis
      diamminedichloroplatinum (CDDP) and mitomycin C (MMC) were administered
      intraperitoneally 3 days prior to surgery, at which time a very viscid peritoneum
      and mucinous intraperitoneal fluid were found in 100% and 83% of the patients,
      respectively. Inflammatory changes were microscopically observed in the
      subserosal layer of the resected stomachs and in the intraperitoneal fluid, but
      degenerative changes characteristic of cancer cells could not be seen. The 3-year
      survival rate of the stage III patients was 55.6%, and peritoneal recurrence was
      found in three of six patients with recurrence. Extensive adhesions were found in
      eight patients (34.8%) as a delayed peritoneal complication, and chronic bowel
      obstruction resulting from the adhesion developed in five patients (21.7%). Thus,
      we conclude that the administration of this IP chemotherapy demonstrated no
      definite antitumor effects or survival benefits, but was frequently associated
      with delayed peritoneal complications.

PMID- 7640467
TI  - Evaluation of aspiration biopsy cytology and combined preoperative tests in the
      diagnosis of breast cancer.
AB  - This study was conducted to investigate the usefulness of aspiration biopsy
      cytology (ABC) and other combined tests for the preoperative diagnosis of breast
      cancer. In an analysis of 599 aspirates of breast tumors, "suspicious" cases were
      included among the positive, while "borderline" cases were considered to be
      negative. The sensitivity of ABC was 87.3%, the specificity was 92.3%, and the
      predictive value of a positive diagnosis was 92.8%. A total of 207 cases of
      breast cancer were evaluated to determine the diagnostic significance of breast
      cancer, particularly for tumors less than 2.0cm by means of quadruple test
      including physical examination, mammography (MMG), ultrasonography (US), and ABC.
      The combined tests of MMG or US, and ABC resulted in a sensitivity of 96.2% and
      94.9%, respectively, and were considered to complement each other in the
      diagnosis of small breast cancer. Surgical biopsy is thus not always necessary in
      malignant cases that are conclusively diagnosed by the combined quadruple test.

PMID- 7640469
TI  - Portal vein embolization with ethanol injection via a fine needle in dogs.
AB  - We devised a method for portal vein embolization with ethanol injection (PVEEI)
      via a fine needle. Both the efficacy and safety of this procedure were evaluated
      in 28 dogs. An embolization of the left central and lateral lobes was undertaken
      with various doses of absolute (95%) ethanol. The smallest dose, 0.25 ml/kg
      ethanol (n = 7), caused the least damage to the liver, but the embolization was
      not complete. At the highest dose at 1.0 ml/kg, four of the seven dogs died of
      respiratory arrest; however, embolization was complete in the remaining dogs. All
      animals tolerated the procedure by 0.5 ml/kg ethanol (n = 11) with a satisfactory
      embolic effect, slight toxicity to the hepatic parenchyma, and only transient
      changes in liver function. The results suggested that PVEEI is safe and effective
      when a suitable dose of ethanol is administered. Local overembolization occurred
      in one dog due to extension of the thrombus, suggesting that the point of
      puncture should not be near the confluence of the branches. Since a selective
      portal venous puncture is not difficult to perform under sonographic guidance,
      PVEEI is expected to be clinically applied.

PMID- 7640468
TI  - Alteration in gastric nerve fibers containing gastrin-releasing peptide in
      relation to the gastrin-producing cell population after truncal vagotomy in a rat
      model.
AB  - The fine structural alteration in the gastric nerve fibers containing gastrin
      releasing peptide (GRP) was studied in relation to the dynamics of gastrin
      producing cells (G-cells) after truncal vagotomy in a rat model. The circulating
      gastrin levels were markedly elevated from the 1st day after vagotomy and the
      number of G-cells with positive immunoreaction for G17 and G34(1-15) was
      significantly increased in the vagotomized group. On the 3rd day after vagotomy,
      the G-cells showed conspicuous ultrastructural changes characterized by
      hypertrophy of the Golgi complexes and increased numbers of secretory granules.
      The GRP-positive nerve fibers formed a fine network in the gastric wall and were
      densely distributed in the oxyntic mucosa close to the blood vessels and showing
      varicosities composed of either small clear or GRP-positive large vesicles
      containing an electron-dense core. In the oxyntic mucosa of the vagotomized rats,
      axonal swelling of the nerves occurred on the 3rd day, and a depletion of GRP
      immunoreactivity was evidenced by a markedly decreased number of large-cored
      vesicles on the 7th day, when the serum GRP levels were also found to be markedly
      elevated. These findings indicate that the alteration in gastric nerve fibers
      containing GRP after truncal vagotomy may be related to hypergastrinemia and
      antral G-cell hyperplasia in the rat gastric mucosa.

PMID- 7640470
TI  - The effects of intraportal prostaglandin E1 administration on hepatic warm
      ischemia and reperfusion injury in dogs.
AB  - To determine the route of prostaglandin E1 (PGE1) administration which would have
      the greatest protective effect against hepatic warm ischemia, two experiments
      were performed using dogs. The pharmacokinetics of PGE1 were investigated in a
      preliminary study, after which, the effects of PGE1 in a 90-min warm ischemic
      liver model were examined. The dogs were divided into three groups of ten,
      according to the treatment given: group A was an untreated control group, group B
      received PGE1 intravenously, and group C received PGE1 intraportally. The PGE1
      was infused continuously at a rate of 0.02 microliters/kg/min before and after
      ischemia. All the dogs in groups A and B died within 24 h of induced ischemia.
      Whereas, six of the ten dogs in group C survived for over 3 days. The arterial
      ketone body ratio was not maintained in groups A and B, but it was in group C.
      Furthermore, in group C the serum lipid peroxide level, which reflects
      hepatocellular membrane damage, was maintained at a lower level than that in the
      other groups after ischemia. Electron microscopy revealed sinusoid destruction
      and changes in both the plasma membrane and parenchymal cell mitochondria in
      groups A and B, while in group C these structures were well preserved. These
      findings confirmed that intraportally administered PGE1 improved the hepatic
      microcirculation and stabilized the hepatocellular membranes. Our results
      indicate that intraportal administration of PGE1 has a greater protective effect
      than intravenous administration against warm ischemic liver injury.

PMID- 7640471
TI  - Auxiliary heterotopic partial liver transplantation in pigs with acute liver
      failure.
AB  - Fulminant hepatic failure is usually fatal without liver transplantation;
      however, orthotopic liver transportation is often difficult to perform due to the
      high risk of coagulopathy and the development of multiple organ failure.
      Auxiliary heterotopic partial liver transplantation (APLT), However, has the
      potential to provide an effective hepatic support system considering that the
      host liver is left in situ and the surgical procedure is less invasive. In this
      report, we describe the beneficial effects of performing 60% APLT on the hepatic
      function and survival of pigs with acute hepatic failure induced by hepatic
      artery ligation. The pigs were divided into a control group of nine animals
      (group 1) that had portal vein and hepatic artery ligation with a side-to-side
      portacaval shunt, and an APLT group of seven animals (group 2) that had portal
      vein and hepatic artery ligation with APLT. The two left lateral lobes of the
      donor liver were resected, reducing the liver weight to about 60%, and the graft
      was placed in the right subhepatic space. No deaths occurred intraoperatively. In
      group 1, eight pigs died of massive liver necrosis within 48 h and one died
      between 48 and 72 h (median survival 23 h). In group 2, two pigs died within 72 h
      due to preservation or anesthetic problems, but five survived for more than 3
      days (median survival 13.4 days), with a significant difference between the two
      groups (P < 0.05). One animal was killed 30 days after APLT and excellent graft
      function was demonstrated by the synthesis of clotting factors, ammonia
      detoxification, and glucohomeostasis. Moreover, evidence of hepatic regeneration
      was found in the transplanted livers.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7640472
TI  - How safe are the xenogeneic hemostats?--Report of a case of severe systemic
      allergic reaction.
AB  - We report herein the unusual case of a 55-year-old woman who developed a severe
      systemic allergy to Avitene (microfibrillar collagen hydrochloride), a xenogeneic
      agent sometimes used for topical hemostasis in laparoscopic cholecystectomy. The
      patient developed fever, general fatigue, mild liver dysfunction, and prominent
      eosinophilia postoperatively. A skin allergy test confirmed that these abnormal
      findings were attributable to an allergic reaction to Avitene.

PMID- 7640473
TI  - Neurofibroma of the stomach: report of a case.
AB  - We report herein the case of a 71-year-old-Japanese woman who was admitted to
      hospital for surgical treatment of a lower abdominal tumor. At laparotomy the
      tumor was found to be pedunculated and growing extramurally from the greater
      curvature of the stomach. Thus, a wedge resection of the stomach, including the
      mass, was performed. The tumor measured about 9 x 8 x 7 cm and histological
      examination of the resected specimen showed that the main elements consisted of
      wavy, long-spindled cells, which crossed irregularly, indicating that it was
      palisading negative. Immunohistochemically, the specimen was positive for both S
      100 protein and Alcian blue. From these findings, the tumor was histologically
      diagnosed as a neurofibroma. The patient had an uneventful postoperative course
      and no signs of recurrence have been recognized in the 3 years since her
      operation.

PMID- 7640474
TI  - A 10-year survivor with unresectable hepatic metastases from sigmoid colon
      carcinoma treated with regional chemotherapy.
AB  - We treated a man with unresectable hepatic metastases from sigmoid colon
      carcinoma who has since survived for more than 10 years. A sigmoidectomy with
      lymph node dissection was performed and a continuous hepatic arterial infusion of
      5-fluorouracil (5-FU) with intermittent infusion of mitomycin C (MMC) was
      administered for about 3 months after this operation. The total doses of 5-FU and
      MMC were 16 g and 84 mg, respectively. Tegafur also was administered orally at a
      dose of 600 mg/day for about 8 months. The carcinoembryonic antigen (CEA) level
      (which had reached 4,409 ng/ml preoperatively) normalized 4 months after surgery,
      and still remains normal. Very few patients with unresectable hepatic metastases
      survive for 5 or more years. However, regional chemotherapy can be effective in
      some patients.

PMID- 7640475
TI  - Minute malignant islet cell tumor of the pancreas: report of a case.
AB  - We present herein the case of a 73-year-old Japanese man in whom a minute
      malignant islet cell tumor, 7 mm in maximal diameter, was discovered. The patient
      was admitted to our hospital to undergo a gastrectomy for gastric cancer, at
      which time preoperative ultrasonography (US) revealed a minute hypoechoic mass
      located in the head of the pancreas. Endoscopic retrograde pancreatography,
      angiography, computed tomography, and magnetic resonance imaging failed to reveal
      the features or location of the tumor; however, these details were obtained by
      endoscopic and intraoperative US. Although intraoperative fine-needle aspiration
      cytology of the tumor enabled a diagnosis of islet cell tumor to be made, it
      failed to provide enough material to evaluate the grade of malignancy, which was
      confirmed by histologic examination of the enucleated tumor, allowing the
      appropriate surgical procedure to be decided.

PMID- 7640476
TI  - Multicentric liposarcoma: report of two cases.
AB  - We present herein two unusual cases of multicentric liposarcoma which highlight
      the problems associated with the management of this disease entity. When the
      surgeon is confronted with multicentric liposarcomas, it is necessary to define
      whether they are secondary tumors or independently arising multicentric
      liposarcomas, since the latter situation merits a more aggressive approach.
      Guidelines for this differentiation are suggested in the discussion following the
      case reports. Surgery, which is often multiple, remains the mainstay of
      treatment, although adjuvant chemotherapy and radiotherapy are also usually
      required.

PMID- 7640477
TI  - Malignant melanoma with mesenteric metastasis causing an intrapelvic abscess:
      report of a case.
AB  - We present herein the case of a 66-year-old woman with disseminated malignant
      melanoma in whom a metastasis in the ileal mesentery ruptured into the peritoneal
      cavity causing an acute abdomen. The patient suddenly developed lower abdominal
      pain and a computed tomography (CT) scan of the pelvis confirmed the presence of
      an intrapelvic abscess. At emergency laparotomy, a 10 x 10 cm ruptured metastatic
      melanoma was found in the ileal mesentery, which demonstrated no communication
      with the ileum itself. To our knowledge, no other case of an acute abdomen being
      caused by the rupture of mesenteric metastatic melanoma lacking any communication
      with the bowel lumen has ever been reported.

PMID- 7640478
TI  - Surgically resected adrenal leiomyoma: report of a case.
AB  - This report describes the case of a 48-year-old woman found to have a leiomyoma
      of the left adrenal gland after presenting with anemia and hypertension. An upper
      gastrointestinal series revealed a mass in the posterior region of the body that
      distorted the stomach. A computed tomography (CT) scan showed a well
      circumscribed mass with a high-density outline in the left adrenal gland, and
      magnetic resonance imaging (MRI) revealed a homogeneous mass. Multiple catheter
      samplings of vena cava blood revealed a slight elevation of epinephrine and
      norepinephrine in the left adrenal vein and the left renal vein. Thus,
      asymptomatic pheochromocytoma of the left adrenal gland was highly suspected as a
      preoperative diagnosis and a left adrenalectomy was performed. However,
      histologic examination subsequently revealed findings suggestive of leiomyoma of
      the adrenal gland, which was confirmed by electron microscopy. The patient's
      postoperative course was uneventful and she has remained free from any further
      symptoms.

PMID- 7640479
TI  - Left ventricular thrombosis following coronary artery bypass grafting in a
      patient with nephrotic syndrome: report of a case.
AB  - We present herein the case of a 63-year-old man with nephrotic syndrome who
      developed an apical infarction 4 days after undergoing coronary artery bypass
      grafting. Echocardiography done 2 weeks postoperatively revealed a left
      ventricular thrombus which was successfully removed. He has no further thrombotic
      events since anticoagulant therapy was initiated.

PMID- 7640480
TI  - Development of a fistula between an internal mammary artery graft and the
      pulmonary vasculature following coronary artery bypass grafting: report of a
      case.
AB  - We report herein the rare case of a 56-year-old man who gradually developed
      congestive cardiac failure 6 months after undergoing coronary artery bypass
      grafting and was found to have a fistula between the internal mammary artery and
      the pulmonary artery of the upper lobe diagnosed by selective left internal
      mammary arteriogram. A second sternotomy was performed and demonstrated dense
      adhesion between the fissure surrounding the internal mammary artery and the
      upper lobe, and the fistula was resected. We believe that the patient's
      increasing cardiac failure was almost certainly caused by coronary seal.

PMID- 7640481
TI  - Spontaneous rupture of the iliac vein: report of a case.
AB  - We report a rare case of a spontaneous rupture of the iliac vein which was then
      surgically treated with good results. A 66-year-old woman was admitted
      complaining of leg swelling and lower abdominal pain. On the 3rd day after
      admission, an operation was performed because of a gradually increasing hematoma
      in the retroperitoneal space. Laparotomy revealed a 17 mm longitudinal tear on
      the anterior surface of the left external iliac vein with a thrombus inside the
      lumen. Most of the previously reported 14 cases of this nature have required
      emergency operations.

PMID- 7640482
TI  - Spontaneous dissecting aneurysm of the main trunk of the superior mesenteric
      artery: report of a case.
AB  - A 47-year-old man with a sudden onset of abdominal pain was diagnosed as having
      an aneurysm of the main trunk of the superior mesenteric artery (SMA), which
      induced ischemic colitis of the transverse colon probably because of a transient
      decrease in the SMA blood flow. The patient was successfully treated by resection
      of the aneurysm and an end-to-side anastomosis of the SMA to the aorta. A
      histological examination revealed a spontaneous dissecting aneurysm of the SMA.

PMID- 7640483
TI  - Ligation of the thoracic duct without thoracotomy as an effective treatment for
      postoperative chylothorax: a newly designed surgical procedure.
AB  - We describe herein a newly designed surgical procedure for ligating the thoracic
      duct to treat postoperative chylothorax, without performing a thoracotomy. This
      technique was successfully performed on a 50-year-old man who developed
      chylothorax following resection of carcinoma of the esophagus whose case is
      briefly presented. The advantages of this procedure include the following: the
      integrity of the thorax is maintained, there is less traumatization, the need for
      a drainage tube is eliminated, shorter hospitalization is required, and the
      thoracic duct is much more easily exposed than by conventional transthoracic
      approaches. No similar report was found in our research of the literature.

PMID- 7640484
TI  - Effect of anti-ICAM-1 and anti-LFA-1 antibodies on rat liver transplantation.
AB  - The effect of the anti-cell adhesion molecule antibodies, anti-ICAM-1 (1A29) and
      anti-LFA-1 (WT1), on rat liver transplantation was investigated. Livers from ACI
      rats were transplanted into Lewis rats by Kamada's method and during the
      recipient operation 1A29 1 mg/kg, and WT1 1 mg/kg were administered intravenously
      to one group of rats (treated group). The survival time of the treated group was
      significantly longer than that of the untreated group, but permanent
      unresponsiveness could not be induced. Postmortem examination revealed little
      histological evidence of acute rejection in treated rats, in which the main cause
      of death was thought to be chronic rejection.

PMID- 7640485
TI  - The applicability of the Kaufman Assessment Battery for Children (K-ABC) with
      older adults (50+ years) with moderate, severe and profound intellectual
      impairment.
AB  - To define the intellectual characteristics of a population of older people (50+
      years) with severe intellectual impairment who were the focus of a wider
      demographic study, participants were assessed on the Kaufman Assessment Battery
      for Children (K-ABC). Test material was modified to make it age-appropriate and
      culturally suitable. Of the 122 people in the population [chronological age (CA)
      = 63.5 years; range 50-90 years], 61 were successfully tested on the K-ABC (CA =
      60.9 years; range 51-81 years). Factor analysis closely replicated the factorial
      structure demonstrated for younger children. Separate Sequential and Simultaneous
      Mental Processing factors were identified, with subtests from the Achievement
      Scale loading on these factors and not constituting a separate factor.
      Application of hierarchical cluster analysis confirmed the factor structures.
      Inferences in relation to cognitive development from a Piagetian perspective are
      drawn, and the utility of information on mental processing for educational
      intervention with older persons with severe intellectual impairment is noted.

PMID- 7640486
TI  - Community adjustment of mobile people with learning difficulties after total
      hospital closure: a preliminary report.
AB  - A study is described in which 50 residents of a hospital for people with learning
      difficulties were assessed immediately before and 1 year after moving into two
      types of community provision; purpose-built campuses or small homes in
      residential streets. Measures were taken of residents' adaptive and unwanted
      behaviours and of aspects of their lifestyles. The results report the changes in
      these measures that were found for both campus and small home residents.

PMID- 7640487
TI  - Assessing clinicians' consultation with people with profound learning disability:
      producing a rating scale.
AB  - This paper describes the development of a scale for assessing clinicians'
      communication with people with profound learning disability. Four psychiatrists
      and four nurses were assessed completing three simple non-invasive clinical
      procedures--blood pressure, pulse and axillary temperature--with people with
      profound learning disability. Videotaped assessment of consultations was
      performed by three experienced speech and language therapists using a previously
      designed scale for analysing encounters with people with mild learning
      disability. This led to the production of a new scale specifically for people
      with profound learning disability. A significant inter-rater reliability was
      found between the three speech therapists for total scores (rater a-b, corr =
      0.654, P = 0.006; rater a-c, corr = 0.795, P = 0.0001: rater b-c, corr = 0.673, P
      = 0.004). Significant reliability between raters was also found for the
      subsections of verbal behaviour and non-verbal behaviour.

PMID- 7640488
TI  - The Reiss Screen for Maladaptive Behaviour: its reliability and internal
      consistencies.
AB  - The inter-rater and test-retest reliabilities, and internal consistencies of the
      Reiss Screen for Maladaptive Behavior (Reiss 1987) were evaluated on a random
      sample of adults with moderate through profound mental retardation living in an
      institutional setting. Generally, the Reiss Screen showed good inter-rater
      reliability, modest to good test-retest and good internal consistency. This
      suggests that the Reiss Screen has moderate to good psychometric robustness.

PMID- 7640489
TI  - The effect of age on language in people with Down's syndrome.
AB  - It has been previously suggested, in a small-sized study of 60 people with Down's
      syndrome, that receptive language skills were lower, the older the individual,
      whereas expressive language skills did not correlate with age (Carter-Young &
      Kramer 1991). By assessing language skills on 345 Down's syndrome adults living
      in Leicestershire (91% of the total population), the present authors have been
      able to confirm this finding, using the AAMD Adaptive Behaviour Scale. This may
      have clinical relevance with regard to communication with older people with
      Down's syndrome, and also for estimation of an individual's skill level when he
      or she was younger.

PMID- 7640490
TI  - Adaptive behaviour after schizophrenia in people with Down's syndrome.
AB  - Seven individuals with Down's syndrome and a past history of schizophrenia were
      matched for age, sex and residence to adults with Down's syndrome but no past
      psychiatric history. The AAMD Adaptive Behaviour Scale was completed for all
      individuals in both groups, at a mean follow-up period of 6.4 years after the
      schizophrenic episode. The skill level of the subject group was found to be the
      same as for the control group, which rejects the notion of a 'defect state'
      occurring post-schizophrenia in Down's syndrome. The importance of accurate
      diagnosis and treatment for this group is stressed.

PMID- 7640491
TI  - Intra-individual factors influencing efficacy of interventions for stereotyped
      behaviours: a meta-analysis.
AB  - The efficacy of treatments targeting stereotyped behaviours has been the focal
      point of several reviews. This study examined efficacy as a function of intra
      individual characteristics, including age, gender, level of disability and
      topography of the behaviour. A meta-analysis of studies reporting treatments of
      stereotyped behaviours appearing in 23 journals over 20 years was conducted.
      Efficacy was determined using two metrics, Percentage Non-overlapping Data and
      Percentage Zero Data, which indicate treatment success as a function of the
      degree to which the behaviour fell below baseline levels, and once reaching zero,
      remained there. Non-parametric analyses indicated differences in treatment
      efficacy according to age and the form of the stereotypy. Implications for the
      design of treatments to address stereotypies are discussed.

PMID- 7640492
TI  - Sentence imitation by adolescents and young adults with Down's syndrome and other
      intellectual disabilities.
AB  - Sentence imitation performance was evaluated longitudinally in 26 adolescents and
      young adults with Down's syndrome (DS), and 26 age- and IQ-matched non-DS
      individuals with other causes of intellectual disability (ID). In each of three
      annual assessments, the DS group began sentence repetitions more slowly and
      imitated sentences less accurately than the ID group. DS sentence repetition
      accuracy was equivalent to the ID group only for two-word sentences and was
      poorer for every other sentence length. Comparisons of sentence imitation and
      auditory digit span scores suggested that only ID subjects benefitted from the
      additional meaning and structure provided by sentences. Correlational analyses
      performed between each year's sentence imitation score and a set of language,
      memory and hearing measures revealed that sentence imitation was related to
      grammatical comprehension, auditory short-term memory and IQ in both groups, and
      to expressive language ability, speed of spoken word processing, speech
      discrimination and acoustic reflexes in the DS group only. A significant
      relationship between sentence imitation and middle-ear functioning was further
      supported by a categorical analysis in which DS subjects with bilateral abnormal
      tympanograms tended to perform more poorly on sentence imitation tasks than DS
      subjects with at least one normal tympanogram. It was concluded that sentence
      imitation is a task that is sensitive to the auditory-perceptual, cognitive and
      expressive difficulties evidenced by individuals with DS.

PMID- 7640493
TI  - Psychotherapeutic approaches in the treatment of mental illness and behavioural
      disorders in mentally retarded people: the significance of a psychoanalytic
      perspective.
AB  - As a result of the increasing preoccupation with pre-oedipal disturbances,
      psychoanalytic theory has had to expand its basis. Through this new
      interpretation, better possibilities for the explanation and treatment of the
      various forms of psychopathology associated with mental retardation emerge. In
      this connection, the notion of a 'persisting developmental deficit' plays an
      important role based on ego-psychology which includes object-relation theory and
      psychoanalytic developmental psychology. Four specific issues illustrate the
      significance of a psychoanalytically orientated approach, namely: (I) the
      transformation of organic brain deficits into mental disorders; (2) 'secondary
      psychosocial deficit'; (3) the significance of the therapeutic relationship; and
      (4) re-enactments as expression of a pathological identity.

PMID- 7640494
TI  - Personality profiles of youngsters with Prader-Willi syndrome and youngsters
      attending regular schools.
AB  - For the study of the personality profile of youngsters with Prader-Willi syndrome
      (PWS), a PWS group was compared with a matched group of youngsters attending
      regular school. The PWS group consisted of 28 youngsters (12 males and 16
      females; mean age 11 years, 11 months). These youngsters were matched on gender
      and age level with 28 youngsters out of a group of 333 youngsters in regular
      school. Behaviour and personality characteristics of each youngster in both
      groups were described by both parents, using a Dutch version of the California
      Child Q-set (CCQ; Block & Block 1980). The present authors compared the scores of
      both groups on eight personality dimensions, derived from the aggregated CCQ
      descriptions for fathers and mothers. The personality dimensions were
      Extraversion, Agreeableness, Conscientiousness, Emotional Stability, Openness,
      Motor Activity, Irritability and Dependency. The authors investigated further
      individual differences of PWS youngsters on the same eight CCQ personality
      dimensions, considering gender and age level as well as IQ level and the presence
      or absence of a 15q11-q13 deletion. The personality profile of PWS youngsters was
      markedly different from youngsters in regular school. Some personality
      characteristics were related to gender and IQ. The lower level of physical
      activity in PWS girls without 15q11-q13 deletion needs further study.

PMID- 7640495
TI  - [Clinical observation on diabetic nephropathy treated with alcohol of Abelmoschus
      manihot].
AB  - Sixty-eight cases of non-insulin dependent diabetes mellitus (NIDDM) complicated
      with nephropathy were randomly divided into two groups: treated group, 35 cases
      treated with alcohol extraction of Abelmoschus manihot, Gliclazide and Captopril
      tablets; control group, 33 cases treated with Gliclazide and Captopril tablets,
      over a period of 8 weeks. The total effective rate in treated and control group
      were 83.87% and 31.03%(P < 0.01), urinary micro-albumin were 31.7 mg/L and 76.3
      mg/L (P < 0.05), proteinuria were 0.41 g/24h and 0.77 g/24h (P < 0.01), blood
      beta 2-microglobulin were 3317.8 ng/ml and 3473.1 ng/ml (P < 0.05), urinary beta
      2-microglobulin were 367.2 ng/ml and 641.5 ng/ml (P < 0.01), urinary N-acetyl
      beta-glucosaminidase (NAG) were 26.3 u/L and 66.7 u/L (P < 0.01), plasma lipid
      peroxide (LPO) were 6.13 nmol/L and 8.78 nmol/L (P < 0.05), and plasma superoxide
      anion were 8.36 kcpm and 10.42 kcpm respectively (P < 0.05). It was suggested
      that Abemoschus manihot alcohol extraction could eliminate oxygen free radicals,
      alleviate renal tubular-interstitial diseases, improve renal function and reduce
      proteinuria.

PMID- 7640496
TI  - [Relationship between various syndrome-types and defect of erythrocyte insulin
      receptors in non-insulin dependent diabetes mellitus].
AB  - Fifty-seven patients of non-insulin dependent diabetes mellitus (NIDDM) were
      divided into various groups by Syndrome Differentiation in TCM and 18 cases of
      non-diabetes mellitus were taken as control. The relationship of Syndrome-types
      and defect of the erythrocyte insulin receptors were studied with the percentage
      of specific insulin binding to erythrocyte, number and average affinity of
      erythrocyte insulin receptors. The results showed: (1) The patients of NIDDM had
      defect of erythrocyte insulin receptors specified with decreased number of
      insulin receptors; (2)Mild defect of erythrocyte insulin receptors was found in
      Syndrome of Yin Deficiency and hyperactivity of Heat, but serious defect in the
      Syndrome of both Qi and Yin Deficiency, in the Syndrome of both Yin and Yang
      Deficiency. Above data suggested that the defect of erythrocyte insulin receptors
      was correlated with Syndrome-types of patients with NIDDM, the more serious
      Deficiency Syndrome, the more serious defect of erythrocyte insulin receptors.

PMID- 7640498
TI  - [Clinical study of improving effect of shuxinyin on abnormal left ventricular
      diastolic function in coronary heart disease].
AB  - There was evidence that abnormal left ventricular diastolic function was common
      in patients with coronary heart disease which led to symptoms such as dyspnea on
      exertion, distress in chest etc, even overt congestive heart failure. The changes
      of left ventricular diastolic function were examined with pulsed doppler
      echocardiography as well as of clinical symptoms, signs, electrocardiographic
      findings and plasma lipoprotein after Shuxinyin (SXY) therapy in 31 patients with
      coronary heart disease and abnormal left ventricular diastolic function. The SXY
      mainly consists of medicinal herbs capable of tonifying Qi and Yin. After
      treatment for one month the symptoms, signs and ECG were improved, the
      symptomatic effective rate was 87.1%. Plasma lipoprotein was reduced (P < 0.05).
      The main changes in doppler echocardiography were as follows. The peak of E wave,
      the area of E wave and Dec rate increased significantly (P < 0.01). The ratio of
      A wave peak to E wave peak was decreased. The changes in peak of A wave, the area
      of A wave and time index were insignificant (P > 0.05). It was concluded that SXY
      mainly improved the early left ventricular diastolic functions, increased the
      peak velocity and volume of rapid left ventricular filling blood flow during the
      early diastole, and thus alleviated symptoms as well as ECG findings.

PMID- 7640497
TI  - [Clinical research of compound salviae miltiorrhizae injection for severe
      pancreatitis].
AB  - Compound salviae miltiorrhizae injection was administered after operation for 28
      cases of severe pancreatitis, and 13 cases were taken as a control group. The
      results showed that: (1) the difference was not obvious in the morbidity of
      complications between the two groups, but the mortality (3.6%) of the trial group
      was significantly lower than that (30.8%) of the control group (P < 0.05); (2)
      Hematocrit was clearly decreased from 46.1 +/- 5.2% to 33.2 +/- 3.9% in the trial
      one (P < 0.05), but platelet and hemoglobin showed no statistical significance.
      It is concluded that compound salviae miltiorrhiza injection might improve
      hemorheologic abnormalities of the disease, promote the recovery of the
      pancreatic tissue, and correct the serious complications such as adult
      respiratory distress syndrome etc.

PMID- 7640499
TI  - [Clinical study in epidural injection with lappaconitine for post-operative
      analgesia].
AB  - This paper studied the effect and side-effect of Lappaconitine for post-operative
      analgesia with epidural injection. 50 patients who were operated in the upper
      abdomen with epidural anesthesia. These patients were randomly divided into 5
      groups. The general condition of every group was similar. Group A, B, C was given
      Lappaconitine 4 ml, 8 ml, 12 ml individually for observation. Group D, E was
      given 0.9% NS 6 ml and morphine 2 mg individually as control. When the operation
      was finished the drug was injected into the epidural space with single blind
      method. The result showed the analgesia of the drug and its effective time was:
      group E > C > B > A > D. The analgesic effect of Group C was satisfactory. The
      efficacy and the maintenance time of A, B, C groups were significantly different
      from that of group D (P < 0.05, P < 0.01). Although the effect of group C was
      less potent than that of group E (morphine injection), there was no side-effect
      as morphine had. It suggested that Lappaconitine for post-operative analgesia
      with epidural injection is effective and safe.

PMID- 7640500
TI  - [Preliminary study on relationship between syndrome differentiation of esophageal
      cancer and changes of exfoliated cells of tongue coating].
AB  - Exfoliated cells of tongue coating of 63 esophageal cancer (EC) cases have been
      investigated by applying exfoliate cytologic examination, which showed that
      abnormal cornified cells were commonly seen while they were less in the patients
      of EC than those in the healthy group, and their difference was significant (P <
      0.05), It showed an increase mainly in the number of pro-cornified cells in the
      patient of the Qi-Yang Deficiency group, an increase mainly in completely
      cornified cells in the Yin Deficiency and an increase in both pro-cornified cells
      and completely cornified cells in Phlegn-Dampness and blood Stasis patients. The
      difference among four groups was significant (P < 0.05). The changes of
      exfoliated cells of tongue coating provided an objective index for the early
      diagnosis of EC.

PMID- 7640501
TI  - [Clinical study on fungus lipid-reducing capsule in regulating lipometabolic
      disorder].
AB  - The patients with lipometabolic disorder were randomly divided into control group
      (70 cases), Fungus Lipid-reducing Capsule (FLC) treated group (70 cases),
      augmented treated group (90 cases). The results shown that: (1) TC and TG were
      reduced markedly in all three groups. The reducing extent in the treated group
      was greater than that in the control group (P < 0.01). HDL-C was increased
      markedly in all three group. The increasing extent in the treated group was
      greater than that in the control group (P < 0.05). These results indicated that
      the effectiveness of FLC was higher than that of control drug in the treatment of
      hyperlipidemia. (2) FLC had obvious effect in improving hemorheology indexes. (3)
      The therapeutic effect of TCM Syndrome-type indicated that FLC could activate the
      Spleen, remove Dampness and nourish the Liver and Kidney.

PMID- 7640502
TI  - [Efficacy of poria-polyporus anti-diarrhea oral liquor in treating infantile
      rotavirus diarrhea: a controlled study with smicta].
AB  - The efficacy of Poria-Polyporus Anti-diarrhea Mixture (PPAM) in infantile
      rotavirus diarrhea with Smicta was observed. In two groups of patients,
      altogether 60 patients were enrolled. The effective rate in the PPAM group and
      Smicta groups were 83.33% and 90.00% (P < 0.05) respectively. No statistically
      significance in respect of the duration of fever and diarrhea. Human rotavirus
      RNA in stool was detected by PAGE, which showed positive result in 13 patients of
      PPAM group and 19 in Smicta group. The duration of virus excretion in both group
      were 2-7 days, which was much shorter than 9-21 days of previous report.

PMID- 7640503
TI  - [Effect of xueguantong on inhibiting experimental atherosclerosis in rabbits].
AB  - In this experiment, the model of experimental atherosclerosis in rabbits was
      established by feeding the cholesterol contained food for 12 weeks. The effect of
      Xueguantong (XGT) in inhibiting atherosclerotic formation in rabbits has been
      studied. It was found that XGT could decrease serum total cholesterol (TC), low
      density lipoprotein cholesterol (LDL-C), platelet aggregation and platelet
      adhesion. The aortic atherosclerotic plaque intimal coverage and ratio of
      atherosclerotic plaque of aortic intimal coverage to aortic medium coverage in
      XGT groups were significantly smaller than that in the model group (P < 0.05).
      The results showed that XGT could inhibit experimental atherosclerotic formation
      in rabbits, it might be relevant to that XGT could reduce the TC and inhibit
      platelet aggregation.

PMID- 7640504
TI  - [Experimental study on effect of sanchaning in treating primary trigeminal
      neuralgia].
AB  - Sanchaning is an empirial prescription in treating primary trigeminal neuralgia
      (PTN). Pills of this prescription have been applied to animal models in an
      experimental study and their effects were compared with that of distilled water
      as well as carbamazepine, a common Western medicine for curing PTN. The indexes,
      including the attack number of PTN of the model animals, the duration of the
      spontaneous reaction and the positive time of the induced response, showed that
      Sanchaning differed significantly from distilled water in treating PTN (P <
      0.01), but slightly differed from that of carbamazepine (P < 0.05). The
      sequential trial has identified that Sanchaning could be used effectively to
      inhibit PTN and has the same effect as carbamazepine. But further study should be
      carried out to investigate the mechanism of its function in relieving PTN.

PMID- 7640505
TI  - [Experimental study on effect of kang ai-bao II to cancer cells with cell CT
      analysis in mice].
AB  - The result of the experiment indicated that Kang Ai-bao II ([symbol: see text]
      II) had a destructive effect on DNA and RNA of cancer cells. Our study provided
      the basis for the clinical practice. The effect of Kang Ai-bao II on U14 cancer
      cell in C57 BL mice was investigated with confocal laser scanning microscopy.

PMID- 7640506
TI  - [Is it possible to study the pharmacokinetics of chemical component of
      decoction?].

PMID- 7640507
TI  - [Progress in the study on antileukemic Chinese herbal drugs and the natural
      medicines].

PMID- 7640508
TI  - [GPT limit values in blood donors: lower, higher or eliminate completely?].

PMID- 7640509
TI  - [Alanine aminotransferase (ALAT, GPT): a reevaluation of exclusion limits for
      blood donors].
AB  - BACKGROUND: The screening policy of alanine aminotransferase (ALT) testing in
      blood donors was reassessed. The cutoff value for ALT levels according to German
      guidelines has always been controversial. In this study the activity and
      distribution of ALT in a blood donor population were reevaluated and new
      exclusion levels were defined. METHODS: 5,706 blood donors were tested for ALT
      activities with the Reflotron system at 37 degrees C. Donors with ALT levels > 51
      IU/l were deferred, a detailed physical examination and additional serologic and
      biochemical testing were done. RESULTS: ALT values of blood donors were
      transformed in logarithmic values in order to get a Gaussian distribution. The
      mean transformed value +/- SD was calculated with 1.24 +/- 0.14 for females and
      with 1.35 +/- 0.16 for males, corresponding to mean values of ALT activity of
      17.6 and 22.5 IU/l, respectively. Exclusion levels of > 33.4 IU/l for female and
      > 46.7 IU/l for male blood donors (geometric mean +2.0 SD) predict a loss of
      donations of 2.8 and 2.7%, respectively, cutoff values of > 39.1 or > 56.1 IU/l
      (geometric mean +2.5 SD) a loss of 1.8 and 1.4%, respectively. The most likely
      causes of elevated ALT levels in 166 of our donors included daily alcohol use
      (82), infections with/without antibiotic medication (29), therapy with
      hepatotoxic drugs (8), strenuous exercises (5), bodybuilding complemented by
      anabolic steroids (2), acute infections with HCV (1), HBV (1) and CMV (1),
      alcohol/drug abuse and detection of HCV antibodies (1). CONCLUSIONS: ALT
      screening is still considered a useful indicator of risk donors despite its
      nonspecificity and limited predictive value. The selection of the appropriate
      cutoff value has always been disputed. The present exclusion level of > 45 IU/l
      (25 degrees C), analogous to > 81.8 IU/l (37 degrees C), does not even take into
      account such a variable as sex. The cutoff value above 4.5 SD of the geometric
      mean for females and above 3.5 SD for males seems to be of limited medical and
      practical value.

PMID- 7640510
TI  - The impact of polymorphonuclear neutrophils on the quality of stored cellular
      blood products.
AB  - BACKGROUND: Storage of blood affects all blood components. Polymorphonuclear
      neutrophils (PMNs) are considered the main culprits of the storage lesion. Their
      prestorage removal improves the quality of blood components. Therefore, they are
      considered of no use in blood transfusion. However, their reduction may remove
      important antibacterial defense mechanisms. METHODS: The phagocytic activity of
      PMNs in whole blood was therefore determined together with additional, sequential
      changes of granula-specific and cytosolic constituents which they release. Blood
      from 12 volunteer donors was analyzed for plasma Na+ and K+, pH, LDH, lysozyme,
      PMN elastase, leukocytes, neutrophils, and neutrophil phagocytosis with
      Phagotest. RESULTS: Leukocytes decreased from (5.0 +/- 1.4) x 10(3) to (3.3 +/-
      1.3) x 10(3) cells/microliter (mean +/- SD), most of them being PMNs. Their
      phagocytic capacity when rewarmed did not change significantly during the first
      24 h of storage, after 3 days it came to a halt. At the same time an increasing
      fall in plasma sodium and pH became apparent, while plasma potassium, LDH,
      lysozyme, and elastase all rose by 427%, 235%, 87% respectively 1,479% at day 11.
      Together with these marker enzymes an armamentarium of antibiotic proteins, other
      proteolytic enzymes, and immunoregulatory molecules is released. CONCLUSION: At
      present, it seems that the bactericidal activity in blood, due to the removal of
      phagocytic PMNs, does not outweight the clinical benefits of an improved
      component preparation where storage lesions are minimized and a number of
      transfusion-associated adverse reactions are avoided.

PMID- 7640511
TI  - Effects of PEEP ventilation on liver metabolism.
AB  - OBJECTIVE: To study the influence of positive endexpiratory pressure (PEEP)
      ventilation on metabolic parameters with specific regard to liver metabolism.
      DESIGN: Prospective experimental study on the effects of PEEP ventilation on
      hemodynamic and gas exchange as well as metabolic parameters, i.e. hepatic
      glucose production, arterial, hepatic and portal venous insulin, glucagon, free
      fatty acid (FFA), glycerol, beta-hydroxybutyrate and lactate concentrations.
      SETTING: Experimental Laboratory Unit of the University Hospital. ANIMALS: 10
      Labrador Beagle dogs (18-22 kg) were studied. INTERVENTIONS: Animals were
      ventilated with PEEP of 0, 7.5, 15, and 0 mm Hg, each level lasting 2 h. RESULTS:
      PEEP 15 significantly increased heart rate from 110(70) to 220(55) beats/min and
      decreased cardiac output from 2.5 (2.0) to 1.5 (0.8) l/min. This was associated
      with significant increases in mean pulmonary artery pressure, pulmonary artery
      occlusion pressure, portal and hepatic venous pressure, whereas mean systemic
      pressure did not change. While whole-body oxygen consumption and respiratory
      quotient remained constant, whole-body oxygen delivery significantly decreased
      from 456(266) to 294(168) ml/min during PEEP 15 concomitant to augmented whole
      body oxygen extraction (from 27(34) to 51(33)%). Oxygen extraction from the
      splanchnic organs increased from 41(31) to 81(30)%. Hepatic venous oxygen tension
      (PhvO2) and hemoglobin oxygen saturation (ShvO2) during PEEP 15 decreased from
      41(18) to 28(47) mm Hg and from 60(31) to 18(66)%, respectively. Hepatic glucose
      production was significantly stimulated from 3.44(1.44) to 3.92(1.83) mg/kg/min
      at PEEP 15. Arterial and portalvenous glucagon/insulin ratios did not change. FFA
      and glycerol concentrations depending on PEEP levels were significantly higher in
      the hepatic artery and portal vein than in the hepatic vein. Compared to portal
      venous and arterial hepatic concentrations, hepatic venous beta-hydroxybutyrate
      significantly increased with rising PEEP levels. CONCLUSIONS: Low values of PhvO2
      and ShvO2 during PEEP 15 gave evidence for hypoxia of the liver. This was
      associated with a stimulated hepatic glucose production rate accompanied by
      enhanced hepatic uptake and utilization of FFA serving as fuel substrates. As the
      rate of gluconeogenesis is a major determinant of hepatic oxygen consumption
      these metabolic effects of PEEP ventilation have to be considered during states
      of critical illness.

PMID- 7640512
TI  - [The legally required guidelines for reporting risks or side-effects caused by
      blood components].
AB  - OBJECTIVE: To prevent dangers to health resulting from the application of drugs,
      the legislator requires the central registration and evaluation of all drug
      risks, especially of side effects and reciprocal effects. Since 1988
      pharmaceutical enterprises have had to denominate a qualified person
      ('Stufenplanbeauftragter') who is responsible for the fulfilment of obligatory
      reporting. In case of complaints or side effects he has to take suitable measures
      according to a special plan ('Stufenplan'). DATA SOURCES: The basis of this
      survey are the legal requirements for drugs ('Arzneimittelgesetz') and
      supplementary regulations which define the duties of the
      'Stufenplanbeauftragter'. RESULTS: Blood components are subject to the legal
      requirements ('Arzneimittelgesetz') without reservations. Therefore the
      corresponding regulations have to be applied without modification in institutes
      for transfusion medicine. In this article the tasks of the
      'Stufenplanbeauftragter' are summarized and practical experience of a university
      institute for transfusion medicine is presented. CONCLUSIONS: In connection with
      the transmission of viral infectious diseases it became evident that the
      'Stufenplanbeauftragter' is very important for the initiation of effective
      measures in case of serious side effects. The security of blood components could
      be improved by the realization of the corresponding legal requirements in the
      institutes for transfusion medicine.

PMID- 7640513
TI  - [Validation of a computer-assisted procedure for producing blood and blood
      component transfusions].
AB  - BACKGROUND: The validation of computer-aided methods in the production of stored
      blood and blood components represents for a pharmaceutical institution a basic
      condition for the carrying out of the decrees of pharmaceutical companies. When
      validating computer-aided methods in medicine or pharmacy, the fields of
      informatics and technology have to be linked to applications in medicine and
      pharmacy. METHOD: In many cases the methods for the documented proof that a
      system achieves the expected capacity are too complex, so that a validation is
      only practicable in module groups. This is shown with an example of the blood
      typing on microtiter plates. RESULTS: After the selection of the hard- and
      software according to the safety criteria of information technology taking into
      consideration functional classes and degrees of quality, a complete documentation
      of the validation of blood typing on the microtiter plate was carried out.

PMID- 7640514
TI  - Metastatic variants of the B16 melanoma: metastasis is related to environmental
      conditions. Phenotypic changes in vitro and metastatic colonization potential in
      nude mice.
AB  - Variants of B16 melanoma exhibit strikingly different metastatic potential in
      AY/a (YB16 tumours) and a/a C57BL/6J (MB16 tumours) syngeneic mice. This study
      focused on relative pigmentation and metastatic potential in eight subline
      cultures initiated from B16 control and YB16 and MB16 tumours. During 6 months of
      in vitro growth in minimal essential medium, cells displayed a continuous
      decrease in their ability to form spontaneous lung colonies in 140 syngeneic mice
      with only persistence of enhanced metastasis-related characteristics depending on
      genetic change in yellow AY/a mice. Conversely, in a parallel experiment in 101
      syngeneic mice in vitro, cells had a greater capacity to generate experimental
      metastases; this might be related to successive different environmental factors.
      In order to compare these prior results obtained in syngeneic mice, the above
      eight secondary cell lines were inoculated subcutaneously into Swiss nude mice.
      The primary tumours thus obtained were then serially transplanted monthly during
      4 months. The new results obtained in a total of 277 mice showed that metastatic
      properties of cells were enhanced or restored in nude mice. Various tumour cell
      environments seem to be responsible for selective pressures that determine the
      melanoma metastatic potential. New, enhanced, heritable, metastasis-related
      characteristics can occur in melanoma cells as a result of genetic and metabolic
      changes and immunologic deficiency of the host. Apparent tumour-host relationship
      should not be neglected, since it has a clear influence on neoplastic diversity
      and malignant behaviour.

PMID- 7640515
TI  - Treatment of nude mice with 4-amidinoindan -1- one2 '- amidinohydrazone, a new S
      adenosylmethionine decarboxylase inhibitor, delays growth and inhibits metastasis
      of human melanoma cells.
AB  - CGP 48664A (4-amidinoindan-1-one2'-amidinohydrazone) is a novel inhibitor of S
      adenosyl-methionine decarboxylase (SAMDC), a key enzyme in the biosynthesis of
      polyamines, which are themselves essential for proliferation of mammalian cells.
      Seven different human melanoma cell lines were treated in vitro with CGP 48664A.
      High, intermediate and low levels of cytostasis were induced in four, one and two
      melanoma lines, respectively. This cytostasis was reversed by the addition of
      exogenous spermidine or spermine to the culture medium. The heterogeneous low
      metastatic (CGP 48664A-resistant) A375P cells and highly metastatic (CGP 48664A
      sensitive) A375SM cells were implanted into the subcutis or injected
      intravenously into nude mice. Systemic daily administration of CGP 48664A
      significantly reduced the size of cutaneous lesions and the number of lung
      metastases in mice implanted with A375SM cells. No beneficial effects were found
      in mice injected with A375P cells. Drug activity was dose dependent, and maximal
      effects were observed when treatment began in mice with small tumour burdens. The
      data suggest that CGP 48664A is effective against melanoma metastasis in nude
      mice and that its activity should be tested in combination with other
      cytoreductive agents.

PMID- 7640516
TI  - The incidence of melanocytic naevi in adolescent children in Queensland,
      Australia.
AB  - The aim of this study was to assess longitudinally the development of melanocytic
      naevi in children around the time of their puberty. In Queensland, Australia, 102
      schoolchildren born mostly in 1977 or 1978, were examined annually on four
      occasions from 1990. All naevi on the body except for the scalp and parts covered
      by a bathing suit were counted by an experienced research nurse or trained
      assistant according to a set protocol. In addition, each subject's pigmentary
      characteristics were recorded and height, weight and pubertal status were
      assessed annually. The findings confirmed that the average number of naevi and
      average density of naevi (count per m2) on the whole body in boys and girls
      increase significantly with increasing age and increases were also seen on each
      of the following anatomic sites: face and neck, back and shoulders, and upper and
      lower limbs. Children who had a high baseline naevus count, or a large increase
      in skin surface area during the 3-year follow-up period had the highest absolute
      increases in naevus count but the smallest proportionate increases. Associations
      between baseline naevus counts and male sex, light brown or blonde hair, blue or
      hazel eyes, facial freckling and a tendency to sunburn, which have been
      previously reported, were also found. However, the independent relations of each
      of these factors to the increase in new naevi were more complex, once the effects
      of high naevus counts at baseline and increases in skin surface area were taken
      into account.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7640517
TI  - A comparative study of atypical and melanocytic naevi on the tropical island
      Curacao and in The Netherlands.
AB  - A cross-sectional study was undertaken in 270 inhabitants of The Netherlands
      (moderate maritime climate, latitude 51 degrees 5' N-53 degrees 3' N) with skin
      types I-III and 757 inhabitants of the tropical island Curacao (latitude 12
      degrees 2' N-12 degrees 23' N). The latter group consisted of 282 White
      individuals (mostly Dutch immigrants) and 475 people with non-White skin types
      IV, V and VI. All participants underwent total skin examination and melanocytic
      naevi (MN) and clinically atypical naevi (AN) were noted. There was no
      statistical difference in the mean number of naevi > or = 2 mm or > or = 5 mm
      between the Curacao and The Netherlands White groups, but the mean number of
      naevi > or = 2 mm and > or = 5 mm was significantly lower in the Curacao non
      White group. We found no obvious differences in mean naevus counts between
      genders and the various comparable age groups. Furthermore, we found no
      significant difference in mean crude and mean age-standardized prevalence of (one
      or more) AN between Whites in The Netherlands and on Curacao. The Mantel-Haenszel
      prevalence ratio weighted for age and gender differences of Curacao Whites vs non
      Whites was 5.93 (95% confidence interval 3.9-12.0), demonstrating that AN are
      significantly less prevalent in darker skin types. In all groups, people with AN
      had significantly more MN than people without AN. We found a generation-dependent
      difference in the expression of AN among White inhabitants of The Netherlands and
      on Curacao, with a higher prevalence of AN in the younger generation.

PMID- 7640518
TI  - CDKN2 explains part of the clinical phenotype in Dutch familial atypical multiple
      mole melanoma (FAMMM) syndrome families.
AB  - Combined multi-point linkage analysis in seven Dutch families with FAMMM syndrome
      confirmed the location of a melanoma susceptibility (MLM) gene in the 9p21 area.
      The occurrence of a shared high-risk haplotype in six of the families strongly
      suggests a founder effect in the Leiden region. No indication for locus
      heterogeneity was observed. Recently, the CDKN2 (p16) gene, an important
      regulator of the cell cycle, was isolated from the 9p21 region. A 19-bp germline
      deletion in the CDKN2 gene was detected in the high-risk haplotype, suggesting
      CDKN2 to be identical to MLM. Loss of heterozygosity studies in melanoma and
      pancreatic carcinoma from gene carriers strongly support the view that CDKN2 is a
      general tumour suppressor gene predisposing not only to melanoma but also to
      other malignancies. Interestingly, the occurrence of apparent clinical FAMMM
      cases with melanoma but without the high-risk deletion haplotype suggests the
      necessity of additional (naevus) genes to explain the complete FAMMM phenotype.

PMID- 7640519
TI  - Serum interleukin-8 (IL-8) is elevated in patients with metastatic melanoma and
      correlates with tumour load.
AB  - It was recently demonstrated that IL-8 is produced by melanoma cell lines and
      acts as an essential autocrine growth factor. We studied the constitutive
      production of IL-8 by melanoma cell lines and the serum concentrations in
      patients with metastatic melanoma. All of 10 melanoma cell lines investigated
      constitutively produced IL-8 (mean 315 +/- 58 pg/10(5) cells per 24 h. IL-8 was
      detectable (mean 159 +/- 13.1 pg/ml) in the serum of 21 out of 56 patients by an
      enzyme-linked immunosorbent assay (ELISA; detection limit < 100 pg/ml). There was
      a significant correlation with tumour load, whereas no correlation with
      metastatic sites was found. No increased IL-8 levels were seen in healthy
      controls or patients with metastatic renal cell carcinoma. These results suggest
      that IL-8 is constitutively produced by melanoma cells in vivo.

PMID- 7640520
TI  - Accumulation of p53 protein in human malignant melanoma. Relationship to clinical
      outcome.
AB  - Paraffin-embedded tissue from the primary tumours of 116 patients with malignant
      melanoma, and in 40 cases also from corresponding metastases, were examined for
      accumulation of p53 protein. The fraction of tumours with positive p53
      immunostaining was 13% in the least invasive and 36% in the most invasive primary
      lesions and 48% in the metastases. Where comparisons could be made, both the
      level and pattern of p53 immunoreactivity were the same in the primary and
      metastatic tumours. Nine (50%) patients with p53-positive and 34 (39%) with p53
      negative primaries relapsed during the first 5 years, but no difference in
      disease-free period was observed between the two groups. However, an overall
      longer survival time was observed among patients with p53-positive primaries,
      especially for those with tumours less invasive than 3.0 mm. Notably, all 11
      patients in this group were alive 5 years after diagnosis of the disease, whereas
      15 out of 70 (21%) patients with p53-negative tumours died in same period. The
      results show that an increased level of p53 protein does not indicate increased
      degree of malignancy in melanoma, but rather suggests a more favourable disease
      progression.

PMID- 7640521
TI  - Elective lymph node dissection in primary malignant melanoma: a matched-pair
      analysis.
AB  - The role of elective lymph node dissection (ELND) in primary malignant melanoma
      is still controversial. Our purpose in this study was to evaluate the benefit
      from ELND on survival and disease-free survival in malignant melanoma of the
      trunk and extremities. We performed a matched-pair analysis on 750 patients.
      There was no significant benefit from wide local excision (WLE) plus ELND
      compared with WLE in the total group. Increased survival rates were noted for
      tumour thicknesses of 1.51-4.0 mm for the WLE+ELND group, as shown by 10-year
      survival rates of 73.1% vs 60.3% (p = 0.14). A significant benefit of ELND was
      detected for malignant melanoma of the trunk (p < 0.05). Disease-free survival
      rates were significantly higher in the collective treated by additional ELND for
      all tumour thicknesses (p < 0.05) and even more in intermediate tumour
      thicknesses of 1.51-4.0 mm (p < 0.001). Our data give further support that ELND
      may be valuable in improving the prognosis in case of malignant melanoma of
      intermediate Breslow thickness.

PMID- 7640522
TI  - Terpenoid metabolism.

PMID- 7640523
TI  - Plant carotenoids: pigments for photoprotection, visual attraction, and human
      health.

PMID- 7640524
TI  - Nitrate: nutrient and signal for plant growth.

PMID- 7640525
TI  - Use of Arabidopsis mutants and genes to study amide amino acid biosynthesis.

PMID- 7640526
TI  - Tryptophan biosynthesis and metabolism: biochemical and molecular genetics.

PMID- 7640527
TI  - Seed storage proteins: structures and biosynthesis.

PMID- 7640528
TI  - Lipid biosynthesis.

PMID- 7640529
TI  - Starch biosynthesis.

PMID- 7640530
TI  - Cellulose biosynthesis.

PMID- 7640531
TI  - Insertion of long term central venous catheters: time for a new look.

PMID- 7640532
TI  - Problem based, small group learning.

PMID- 7640534
TI  - Dutch face up to blood scandal.

PMID- 7640533
TI  - Cycling, physical exercise, and the millennium fund.

PMID- 7640535
TI  - Studies highlight chemical threats to reproduction.

PMID- 7640536
TI  - Israeli court paves way for surrogacy.

PMID- 7640537
TI  - Nestle appears in court in India.

PMID- 7640538
TI  - Randomised comparison of chiropractic and hospital outpatient management for low
      back pain: results from extended follow up.
AB  - OBJECTIVE: To compare the effectiveness over three years of chiropractic and
      hospital outpatient management for low back pain. DESIGN: Randomised allocation
      of patients to chiropractic or hospital outpatient management. SETTING:
      Chiropractic clinics and hospital outpatient departments within reasonable
      travelling distance of each other in 11 centres. SUBJECTS: 741 men and women aged
      18-64 years with low back pain in whom manipulation was not contraindicated.
      OUTCOME MEASURES: Change in total Oswestry questionnaire score and in score for
      pain and patient satisfaction with allocated treatment. RESULTS: According to
      total Oswestry scores improvement in all patients at three years was about 29%
      more in those treated by chiropractors than in those treated by the hospitals.
      The beneficial effect of chiropractic on pain was particularly clear. Those
      treated by chiropractors had more further treatments for back pain after the
      completion of trial treatment. Among both those initially referred from
      chiropractors and from hospitals more rated chiropractic helpful at three years
      than hospital management. CONCLUSIONS: At three years the results confirm the
      findings of an earlier report that when chiropractic or hospital therapists treat
      patients with low back pain as they would in day to day practice those treated by
      chiropractic derive more benefit and long term satisfaction than those treated by
      hospitals.

PMID- 7640539
TI  - Using decision analysis to compare policies for antenatal screening for Down's
      syndrome.
AB  - OBJECTIVE: To compare different screening policies for Down's syndrome across a
      broad range of outcomes, using decision analysis, with particular reference to
      the role of maternal serum testing. DESIGN: A decision tree was used to combine
      data from local sources and the medical literature to predict the likely
      frequency of several outcomes. Sensitivity analyses were used to test the
      robustness of the conclusions drawn. SETTING: Oxfordshire Health Authority. MAIN
      OUTCOME MEASURES: Live births with and without Down's syndrome; miscarriages with
      Down's syndrome; cases of Down's syndrome detected antenatally; amniocenteses
      performed (and associated miscarriages); direct NHS screening costs; number of
      women offered screening. RESULTS: Screening policies for Down's syndrome that
      include serum testing can produce better population outcomes than programmes that
      do not. Each option for screening for Down's syndrome that we considered had
      significant drawbacks. In Oxfordshire, offering serum testing to women of all
      ages would prevent the birth of approximately one more baby with Down's syndrome
      per year than would a policy of screening for women aged 30 years or more. The
      cost of preventing this one extra Down's birth would be one or two normal babies
      lost after amniocentesis, 4500 blood tests for young women (with the associated
      anxiety and counselling), approximately 200 false positive serum test results and
      amniocenteses (with the associated anxiety and distress), and 90,000 pounds for
      the extra tests, counselling, and amniocenteses. Opinions are divided as to which
      policy is the better option for the population. CONCLUSIONS: Decision analysis is
      a useful tool for determining the likely consequences of different policy options
      across a broad range of outcomes. This focuses debate and decision making on
      outcomes of care, which in turn makes it clear that the choice of screening
      programme for Down's syndrome depends on the relative importance ascribed to the
      different outcomes. If individuals' values vary widely it may be impossible to
      find one screening policy that meets the needs of all pregnant women.

PMID- 7640540
TI  - Period trends in rate of suicide in first 28 days after discharge from
      psychiatric hospital in Scotland, 1968-92.
AB  - OBJECTIVE: To examine period trends in the rate of suicide in the first 28 days
      after discharge from psychiatric hospital. DESIGN: Cohort study of patients
      discharged from psychiatric hospital. SETTING: Scotland. SUBJECTS: All patients
      aged 15-84 who were discharged from Scottish psychiatric hospitals during 1968 to
      1992. OUTCOME MEASURE: The rate of suicide (classified as codes E950-9 and E980-9
      according to the International Classification of Diseases, Ninth Revision) within
      28 days of discharge per 100,000 person years at risk for five year periods
      during 1968 to 1992. Crude, within cohort rates and externally standardised rates
      were calculated. RESULTS: Overall, 196 male patients committed suicide in 20,520
      person years at risk, and 171 female patients committed suicide in 24,114 person
      years at risk. A significant linear trend was seen in period effect on externally
      standardised mortality ratios in both sexes: a decrease in male patients (P =
      0.008) and an increase in female patients (P = 0.0001). The adjusted standardised
      mortality ratio in 1988-92 compared with 1968-72 was 0.62 (95% confidence
      interval 0.39 to 0.98) in male patients and 2.73 (1.64 to 4.56) in female
      patients. CONCLUSION: The increase in the rate of suicide in the 28 days after
      discharge in female psychiatric patients makes this an increasingly important
      period to target. The rise has occurred against the background of a reduction of
      60% in the number of psychiatric beds for adults.

PMID- 7640541
TI  - A survey of acute pain services in the United Kingdom.

PMID- 7640542
TI  - Pulmonary oedema and haemoptysis induced by strenuous swimming.

PMID- 7640543
TI  - Trends in prescriptions of paracetamol for children.

PMID- 7640544
TI  - Double blind trial of repeated treatment with transdermal nicotine for relapsed
      smokers.
AB  - OBJECTIVE: To assess the efficacy and safety of a repeat course of treatment with
      transdermal nicotine for cessation of smoking in a brief intervention setting.
      STUDY DESIGN: Randomised, double blind, placebo controlled trial with follow up
      for 26 weeks. SUBJECTS: 629 smokers who had unsuccessfully attempted to stop
      smoking by using active transdermal nicotine and brief behavioural counselling.
      Smokers were motivated to quit smoking for a second time and smoked > or = 15
      cigarettes a day. INTERVENTIONS: Twelve weeks' treatment with active transdermal
      nicotine patches or placebo and brief counselling at monthly visits. MAIN OUTCOME
      MEASURE: Sustained smoking cessation for the 28 days before the visit at week 12
      verified by expired carbon monoxide concentrations. RESULTS: At 12 weeks 21/315
      (6.7%) subjects allocated to active treatment had stopped smoking compared with
      6/314 (1.9%) allocated to placebo (absolute difference 4.7%; 95% confidence
      interval 1.6% to 7.9%; P = 0.003). At 26 weeks the rates were 20/315 (6.4%) and
      8/314 (2.6%) (3.8%; 0.6% to 7.0%; P = 0.021). Difficulty in sleeping was reported
      by 43/179 (24.0%) on active treatment and 19/143 (13.3%) on placebo (P = 0.015).
      Severe reactions at the site of application were rare (6/322; 1.9%). CONCLUSIONS:
      Repeated treatment with transdermal nicotine together with brief counselling can
      improve the low success rates of smoking cessation in recently relapsed, moderate
      to heavy smokers. Questions remain about whether more intensive interventions or
      higher doses of nicotine could be more effective. The likelihood of severe
      reactions at the site of application with repeated treatment is low.

PMID- 7640545
TI  - Pulse oximetry: a practical review.

PMID- 7640546
TI  - Development of review criteria: linking guidelines and assessment of quality.
AB  - Review criteria are designed to enable clinicians and others to assess care.
      However, there is no established method for developing criteria, and they are
      often confused with guidelines. Criteria should comprise measurable activities
      that are appropriate for the setting in which they are to be used. They should
      also be based on research evidence and prioritised according to the strength of
      that evidence and effect on outcome. Good criteria can be used to aid
      implementation of guidelines by providing a standard against which to monitor
      performance and enabling clinical audit.

PMID- 7640547
TI  - Commentary: the perils of checklist medicine.

PMID- 7640548
TI  - Managing in flight emergencies.

PMID- 7640550
TI  - ABC of medical computing. Linking your computer to the outside world.

PMID- 7640549
TI  - Consensus methods for medical and health services research.
AB  - Health providers face the problem of trying to make decisions in situations where
      there is insufficient information and also where there is an overload of (often
      contradictory) information. Statistical methods such as meta-analysis have been
      developed to summarise and to resolve inconsistencies in study findings--where
      information is available in an appropriate form. Consensus methods provide
      another means of synthesising information, but are liable to use a wider range of
      information than is common in statistical methods, and where published
      information is inadequate or non-existent these methods provide a means of
      harnessing the insights of appropriate experts to enable decisions to be made.
      Two consensus methods commonly adopted in medical, nursing, and health services
      research--the Delphi process and the nominal group technique (also known as the
      expert panel)--are described, together with the most appropriate situations for
      using them; an outline of the process involved in undertaking a study using each
      method is supplemented by illustrations of the authors' work. Key methodological
      issues in using the methods are discussed, along with the distinct contribution
      of consensus methods as aids to decision making, both in clinical practice and in
      health service development.

PMID- 7640551
TI  - Strategy needed for adolescent patients with cancer.

PMID- 7640552
TI  - Treatment for cancer pain in France.

PMID- 7640553
TI  - Pneumococcal vaccine for HIV patients. Patients with HIV infection should be
      immunised...

PMID- 7640554
TI  - Surgical bleeding and calcium antagonists. Incidence of bleeding may be lower
      than suggested.

PMID- 7640555
TI  - Surgical bleeding and calcium antagonists. Other causes for increased risk of
      bleeding are possible.

PMID- 7640556
TI  - Faulty blood bags. Faulty bags were withdrawn from routine use.

PMID- 7640557
TI  - Faulty blood bags. Reputation of English blood transfusion service has been
      unjustly damaged.

PMID- 7640558
TI  - Screening for melanoma.

PMID- 7640559
TI  - Labour and birth in water. Safety has yet to be determined.

PMID- 7640560
TI  - Place of tricyclics in depression of young people is not proved.

PMID- 7640561
TI  - Labour and birth in water. Temperature of pool is important.

PMID- 7640562
TI  - Treatment in the air. Strategy of descent is not without risk.

PMID- 7640563
TI  - Non-steroidal anti-inflammatory drugs in elderly people. Enteric coated aspirin
      may reduce risk.

PMID- 7640564
TI  - Non-steroidal anti-inflammatory drugs in elderly people. Treat mild chronic pain
      with paracetamol initially.

PMID- 7640565
TI  - Non-steroidal anti-inflammatory drugs in elderly people. Gastrointestinal
      bleeding is common.

PMID- 7640566
TI  - Non-steroidal anti-inflammatory drugs in elderly people. Mefenamic acid is more
      dangerous than most.

PMID- 7640567
TI  - Rethinking consultants.

PMID- 7640568
TI  - Continuing medical education. College programme will be acceptable to clinicians.

PMID- 7640569
TI  - Continuing medical education. Competence and performance are measurable but do
      not equate with practice.

PMID- 7640570
TI  - Assessing quality of economic submissions to the BMJ.

PMID- 7640571
TI  - Adjusting for underenumeration in the 1991 census.

PMID- 7640572
TI  - Deputising general practitioners' role in emergencies.

PMID- 7640573
TI  - Journals sponsored by single companies.

PMID- 7640574
TI  - Air pollution and health.

PMID- 7640575
TI  - British government's proposals on poorly performing doctors.

PMID- 7640576
TI  - Sex and HIV/AIDS education in schools.

PMID- 7640578
TI  - Doctors could oppose child's right to die.

PMID- 7640577
TI  - Triage in accident and emergency departments.

PMID- 7640579
TI  - US report denies that gulf war syndrome is disease.

PMID- 7640580
TI  - Government wants doctors to report unfit colleagues.

PMID- 7640581
TI  - Russia delays HIV testing for foreigners.

PMID- 7640582
TI  - Illinois sanctions doctor's role in executions.

PMID- 7640583
TI  - Cut red tape for GPs, urges report.

PMID- 7640584
TI  - Low serum total cholesterol concentrations and mortality in middle aged British
      men.
AB  - OBJECTIVE: To examine the relation between low serum total cholesterol
      concentrations and causes of mortality. DESIGN: Cohort study of men followed up
      for an average of 14.8 years (range 13.5-16.0 years). SETTING: One general
      practice in each of 24 British towns. SUBJECTS: 7735 men aged 40-59 at screening
      selected at random from the 24 general practices. MAIN OUTCOME MEASURES: Deaths
      from all causes, cardiovascular causes, cancer, and non-cardiovascular, non
      cancer causes. RESULTS: During the mean follow up period of 14.8 years there were
      1257 deaths from all causes, 640 cardiovascular deaths, 433 cancer deaths, and
      184 deaths from other causes. Low serum cholesterol concentrations (< 4.8
      mmol/l), present in 5% (n = 410) of the men, were associated with the highest
      mortality from all causes, largely due to a significant increase in cancer deaths
      (age adjusted relative risk 1.6 (95% confidence interval 1.1 to 2.3); < 4.8 v 4.8
      5.9 mmol/l) and in other non-cardiovascular deaths (age adjusted relative risk
      1.9 (1.1 to 3.1)). Low serum cholesterol concentration was associated with an
      increased prevalence of several diseases and indicators of ill health and with
      lifestyle characteristics such as smoking and heavy drinking. After adjustment
      for these factors in the multivariate analysis the increased risk for cancer was
      attenuated (relative risk 1.4 (0.9 to 2.0) and the inverse association with other
      non-cardiovascular, non-cancer causes was no longer significant (relative risk
      1.5 (0.9 to 2.6); < 4.8 v 4.8-5.9 mmol/l). The excess risks of cancer and of
      other non-cardiovascular deaths were most pronounced in the first five years and
      became attenuated and non-significant with longer follow up. By contrast, the
      positive association between serum total cholesterol concentration and
      cardiovascular mortality was seen even after more than 10 years of follow up.
      CONCLUSION: The association between comparatively low serum total cholesterol
      concentrations and excess mortality seemed to be due to preclinical cancer and
      other non-cardiovascular diseases. This suggests that public health programmes
      encouraging lower average concentrations of serum total cholesterol are unlikely
      to be associated with increased cancer or other non-cardiovascular mortality.

PMID- 7640585
TI  - School sex education: an experimental programme with educational and medical
      benefit.
AB  - OBJECTIVES: To develop and teach a school sex education programme that will lead
      to a decrease in sexual activity. DESIGN: A matched internal and external control
      experiment, comparing control populations which received their own sex education
      programmes with populations which received a novel sex education intervention
      that included medical and peer led teaching. SETTING: Comprehensive secondary
      schools; control and intervention populations within Devon, and distant controls
      from rural, semiurban, and urban areas of England excluding major conurbations.
      SUBJECTS: Schoolchildren were taught from age 12 to 16; three successive cohorts
      of students were evaluated in school year 11 (mean age 16.0). MAIN OUTCOME
      MEASURES: Questionnaire conducted under "examination conditions" and invigilated
      by the research team and other trained medical staff. RESULTS: In the
      intervention population, progressive increase in knowledge related to
      contraception, sexually transmitted diseases, and prevalence of sexual activity
      (chi 2 (trend) P < 0.001 for all three series); relative increase between
      intervention and control populations in knowledge, relative decrease in attitudes
      suggesting that sexual intercourse is of itself beneficial to teenagers and their
      relationships, relative decrease in sexual activity, and relative increase in
      approval of their "sex education" (relative risk > 1.00 with 95% confidence
      limits not including 1.00 for all series and for comparisons with both control
      populations); odds ratio (control v programme) for sexual activity of 1.45,
      controlling for sociodemographic variables. CONCLUSION: School sex education that
      includes specific targeted methods with the direct use of medical staff and peers
      can produce behavioural changes that lead to health benefit.

PMID- 7640586
TI  - Provision of sex education and early sexual experience: the relation examined.
AB  - OBJECTIVES: To explore the relation between receipt of sex education and
      experience of first intercourse. SUBJECTS AND DESIGN: The national survey of
      sexual attitudes and lifestyles is based on a sample of 18,876 respondents aged
      16-59, randomly selected from the Post Office's small-user postcode address file.
      Data were collected between May 1990 and November 1991 by personal interviews
      combining a self administered questionnaire with a face to face interview. MAIN
      OUTCOME MEASURES: Age at first intercourse, use of contraception at first
      intercourse, actual and preferred source of sex education (including school based
      lessons). RESULTS: Median age at first intercourse fell by four years for women
      and three years for men over the past four decades, to 17 for both men and women
      aged 16-19 at the time of interview. Of those respondents for whom school was the
      main source of information about sexual matters, men were less likely, and women
      no more likely, to have had intercourse before the age of 16 than were those
      citing other main sources, such as friends and the media. Both men and women were
      more likely to have used some method of contraception. In multivariate analysis,
      these effects remained after controlling for the effect of current age,
      educational attainment, and religious affiliation. CONCLUSIONS: These data
      provide no evidence to support the concern that provision of school sex education
      might hasten the onset of sexual experience. These findings have important
      implications for the provision of sexual health education and highlight the need
      to carry out prospective and randomised studies of the impact of sex education.

PMID- 7640587
TI  - Complications at site of injection of depot neuroleptics.

PMID- 7640588
TI  - Exacerbation of idiopathic Parkinson's disease by naproxen.

PMID- 7640589
TI  - Interaction between cyclosporin and fluoxetine.

PMID- 7640590
TI  - Transverse myelitis after measles, mumps, and rubella vaccine.

PMID- 7640592
TI  - Primary care in the accident and emergency department: II. Comparison of general
      practitioners and hospital doctors.
AB  - OBJECTIVE: To compare the process and outcome of "primary care" consultations
      undertaken by senior house officers, registrars, and general practitioners in an
      accident and emergency department. DESIGN: Prospective, controlled intervention
      study. SETTING: A busy, inner city accident and emergency department in south
      London. SUBJECTS: Patients treated during a stratified random sample of 419 three
      hour sessions between June 1989 and May 1990 assessed at nurse triage as
      presenting with problems that could be treated in a primary care setting. 1702 of
      these patients were treated by sessionally employed local general practitioners,
      2382 by senior house officers, and 557 by registrars. MAIN OUTCOME MEASURES:
      Process variables: laboratory and radiographic investigations, prescriptions, and
      referrals; outcome variables: results of investigations. RESULTS: Primary care
      consultations made by accident and emergency medical staff resulted in greater
      utilisation of investigative, outpatient, and specialist services than those made
      by general practitioners. For example, the odds ratios for patients receiving
      radiography were 2.78 (95% confidence interval 2.32 to 3.34) for senior house
      officer v general practitioner consultations and 2.37 (1.84 to 3.06) for
      registrars v general practitioners. For referral to hospital specialist on call
      teams or outpatient departments v discharge to the community the odds ratios were
      2.88 (2.39 to 3.47) for senior house officers v general practitioners and 2.57
      (1.98 to 3.35) for registrars v general practitioners. CONCLUSION: Employing
      general practitioners in accident and emergency departments to manage patients
      with primary care needs seems to result in reduced rates of investigations,
      prescriptions, and referrals. This suggests important benefits in terms of
      resource utilisation, but the impact on patient outcome and satisfaction needs to
      be considered further.

PMID- 7640591
TI  - Primary care in the accident and emergency department: I. Prospective
      identification of patients.
AB  - OBJECTIVE: To compare patient characteristics and consultation activities for
      attenders at accident and emergency departments assessed by nurse triage as
      presenting with "primary care" or "accident and emergency" type problems. DESIGN:
      One year prospective study. SETTING: A busy, inner city accident and emergency
      department in south London. SUBJECTS: Of the 5658 patients treated for new
      problems during a stratified random sample of 204 three hour sessions between 10
      am and 9 pm during June 1989 to May 1990, all "primary care" (2065 patients) and
      a 10% random sample of "accident and emergency" (291 patients) were included in
      the analysis. MAIN OUTCOME MEASURES: Patient's age, sex, duration of presenting
      problem, diagnosis, laboratory and radiographic investigations, treatments, and
      referrals. RESULTS: 40.9% of attenders with new problems were classified by
      triage as presenting with "primary care" problems (95% confidence interval 39.6%
      to 42.2%). Primary care attenders were more likely than accident and emergency
      patients to be young adults, to have symptoms with a duration of longer than 24
      hours, and to present problems not related to injury (all P < 0.001). Accident
      and emergency patients were considerably more likely to be referred to on call
      teams and to be admitted. Even so, 9.7% of primary care patients were referred to
      on call teams and a further 8.9% were referred to the fracture clinic or advised
      to return to the accident and emergency department for follow up. CONCLUSION:
      Accident and emergency triage can be developed to identify patients with problems
      that are more likely to be of a primary care type, and these patients are less
      likely to receive an investigation, minor surgical procedure, or referral. Many
      patients in this category, however, receive interventions likely to support their
      decision to attend accident and emergency rather than general practice. This may
      reflect limitations in the sensitivity of triage practice or a clinical approach
      of junior medical staff that includes a propensity to intervene.

PMID- 7640593
TI  - Observations on the NHS internal market: will the dodo get the last laugh?
AB  - Distinguishing between the theory and practice of the internal market has been
      obscured by the considerable controversy generated by the reforms themselves. In
      such an environment both the advocates and the opponents of a market based
      solution have tended to promote their respective claims by reference to
      underlying political philosophies and economic theories rather than practical
      experience. Royce gives his observations of the actual operation of the internal
      market with particular reference to the commissioning function in Wales. He
      highlights inadequacies and inequities in the current system and proposes some
      remedial actions. Central to these are the importance of ensuring equitable
      funding for all purchasers, acknowledging the necessity of rationing, and
      promoting efficient and effective health care, sometimes at the expense of
      patient choice and guaranteed local service provision.

PMID- 7640594
TI  - Cambodian health in transition.
AB  - As conflict and suffering in Bosnia, Chechnya, Rwanda, and Zaire continue to be
      at the forefront of world attention, some countries seem to be largely forgotten.
      It is timely to take stock of conditions in the small country of Cambodia as it
      struggles to take its place after a long period of isolation. Countless
      Cambodians and ethic Vietnamese have died there this year and during the past 25
      years, victims of senseless killing or preventable disease.

PMID- 7640596
TI  - Case study evaluation.
AB  - Case study evaluations, using one or more qualitative methods, have been used to
      investigate important practical and policy questions in health care. This paper
      describes the features of a well designed case study and gives examples showing
      how qualitative methods are used in evaluations of health services and health
      policy.

PMID- 7640595
TI  - Obesity in Britain: gluttony or sloth?
AB  - The prevalence of clinical obesity in Britain has doubled in the past decade. The
      Health of the Nation initiative has set ambitious targets for reversing the trend
      in recognition of the serious health burden which will accrue, but efforts to
      develop prevention and treatment strategies are handicapped by uncertainty as to
      the aetiology of the problem. It is generally assumed that ready access to highly
      palatable foods induces excess consumption and that obesity is caused by simple
      gluttony. There is evidence that a high fat diet does override normal satiety
      mechanisms. However, average recorded energy intake in Britain has declined
      substantially as obesity rates have escalated. The implication is that levels of
      physical activity, and hence energy needs, have declined even faster. Evidence
      suggests that modern inactive lifestyles are at least as important as diet in the
      aetiology of obesity and possibly represent the dominant factor.

PMID- 7640597
TI  - Is it time to stop using chloramphenicol on the eye? Fears are based on only six
      cases.

PMID- 7640598
TI  - Is it time to stop using chloramphenicol on the eye? Safe in patients with no
      history of blood dyscrasia.

PMID- 7640599
TI  - Is it time to stop using chloramphenicol on the eye? Risk is low in short
      courses.

PMID- 7640600
TI  - Is it time to stop using chloramphenicol on the eye? Prospective study of
      aplastic anaemia should give definitive answer.

PMID- 7640601
TI  - Is it time to stop using chloramphenicol on the eye? General practitioners would
      expect to see aplasia roughly once each century.

PMID- 7640602
TI  - Should herbal medicines be licensed?

PMID- 7640603
TI  - Monitoring during endoscopy. Attention to sedation techniques may reduce
      mortality.

PMID- 7640604
TI  - Monitoring during endoscopy. Gastric lavage poses risks to patient.

PMID- 7640605
TI  - Monitoring during endoscopy. Pulse oximetry has limitations.

PMID- 7640606
TI  - Monitoring during endoscopy. Paediatric endoscopy should be carried out under
      general anaesthesia.

PMID- 7640607
TI  - Monitoring during endoscopy. Hypoxia during endoscopy also occurs in unsedated
      patients.

PMID- 7640608
TI  - Monitoring during endoscopy. Italian data support upper gastrointestinal
      endoscopy without sedation.

PMID- 7640609
TI  - Open access echocardiography.

PMID- 7640610
TI  - Patients' perceptions of need for primary health care services. Patients could
      consider general good rather than their own.

PMID- 7640611
TI  - Measuring NHS activity. Admission rates are misleading.

PMID- 7640612
TI  - Measuring NHS activity. General household survey provides valuable data.

PMID- 7640613
TI  - Polymyalgia rheumatica and giant cell arteritis. High dose corticosteroids are
      recommended.

PMID- 7640614
TI  - Polymyalgia rheumatica and giant cell arteritis. Synovitis and polymyalgia
      rheumatica can coexist.

PMID- 7640616
TI  - Accrediting hospitals.

PMID- 7640615
TI  - Polymyalgia rheumatica and giant cell arteritis. Consider prophylaxis for steroid
      induced osteoporosis.

PMID- 7640617
TI  - General practitioners' separate out of hours contract. Accident departments
      cannot guarantee cover if GPs opt out.

PMID- 7640619
TI  - A danger to health.

PMID- 7640618
TI  - General practitioners' separate out of hours contract. Fundamental review of
      primary and secondary emergency services is required.

PMID- 7640620
TI  - Midsummer madness: x rays and breast cancer.

PMID- 7640621
TI  - Thyroid calorigenesis and oxidative stress: modification of the respiratory burst
      activity in polymorphonuclear leukocytes.
AB  - 1. Recent research on experimental animals indicates that thyroid hormone
      administration is associated with greater electron flow through the microsomal,
      mitochondrial, and peroxisomal electron transport systems of the liver, as
      indicated by the enhanced production of superoxide radicals (O2.-) and/or
      hydrogen peroxide (H2O2). 2. Hyperthyroidism induces an increased respiratory
      burst activity in rat and human polymorphonuclear leukocytes, an effect that
      seems to be related to changes in the myeloperoxidase-H2O2 system of the cell,
      rather than to the direct actions of the hormone or changes in the opsonic
      capacity of plasma. 3. These findings indicate that thyroid calorigenesis
      involves an elevated prooxidant activity in target cells, which may be relevant
      in determining toxic effects within the tissue or in neighboring cells.

PMID- 7640622
TI  - Molecular structure and long-range functional linkage of phosphorylation and
      cation binding domains in the Ca2+ transport ATPase.

PMID- 7640623
TI  - Effect of mild iron overload on liver and kidney lipid peroxidation.
AB  - 1. Hepatotoxicity is the most common finding in patients with iron overload since
      the liver is the major recipient of iron excess, even though the kidney could be
      a target of iron toxicity. The effect of iron overload was studied in the early
      stages after iron-dextran injection in rats, as a model for secondary
      hemocromatosis. 2. Total hepatic and kidney iron content was markedly elevated
      over control values 20 h after the iron administration. Plasma GOT, GPT and LDH
      activities were not affected, suggesting that liver cell permeability was not
      affected by necrosis. 3. Spontaneous liver chemiluminescence was measured as an
      indicator of oxidative stress and lipid peroxidation. Light emission was
      increased four-fold 6 h after iron supplementation. 4. Increases in the
      generation of thiobarbituric acid reactive substances (TBARS in liver and kidney
      homogenates were detected after iron administration. 5. The activities of
      catalase, SOD and glutathione peroxidase were determined. Enzymatic activities
      declined in liver homogenates by 25, 36 and 32%, respectively, 20 h after iron
      injection. These activities were not affected in kidney as compared to control
      values, except for SOD activity that was decreased by 26%. 6. The content of
      alpha-tocopherol was decreased by 31% in whole kidney homogenates and by 40% in
      plasma. 7. Our data indicate that lipid peroxidation occurs after mild iron
      overload both in liver and kidney. Enzymatic antioxidants are consumed
      significantly in liver and alpha-tocopherol content decreases in kidney,
      suggesting an organ-specific antioxidant effect.

PMID- 7640624
TI  - The gene encoding eIF-2 beta in S. cerevisiae maps to chromosome XVI.
AB  - The gene encoding the beta subunit of the translation initiation factor eIF-2 in
      the yeast Saccharomyces cerevisiae was mapped by physical methods to the distal
      part of the left arm of chromosome XVI, adjacent to the HSP90 locus. This
      assignment was confirmed by genetic linkage data with the GAL4 locus.

PMID- 7640625
TI  - Isolation and characterization of c-fos recombinant baculovirus.
AB  - The use of the baculovirus system to produce recombinant proteins is based on the
      high level of protein production and the possibility to obtain, in Spodoptera
      frugiperda insect cells, recombinant proteins with the post-translational
      modifications found in the native proteins. Here we describe the isolation and
      characterization of a recombinant baculovirus containing the mouse c-fos gene.
      The c-fos cDNA was subcloned into the pVL1392 baculovirus transfer vector. The
      recombinant plasmid (pVL1392.fos) was introduced into Sf9 insect cells by co
      transfection with viral wild-type DNA. Upon selection and characterization of a
      viral recombinant clone, Sf9 cells were infected with this virus stock and the
      cFos protein expression was detected by immunological methods using an anti-cFos
      polyclonal antiserum.

PMID- 7640626
TI  - A scanning electron microscope investigation of calcium fluoride-like material
      deposited during topical fluoride exposure on sound human enamel in vitro.
AB  - 1. The morphological aspects of globules deposited in vitro when a NaF solution
      is applied to sound human enamel were studied by scanning electron microscopy. 2.
      Particles, presumably of calcium fluoride-like material, formed on the surfaces
      of an unerupted tooth and consisted of subunits showing a "cauliflower"
      appearance, indicating agglomeration of even smaller particles. The number and
      size of the crystals increased with time of exposure. 3. These particles
      represent highly resistant fluoride reservoirs and may be of clinical
      significance.

PMID- 7640627
TI  - Development and clinical application of an immunofluorometric assay for intact
      parathyroid hormone.
AB  - Parathyroid hormone (PTH) is a linear peptide of 84 amino acids that is found in
      serum mainly in the form of carboxyl-terminal fragments. The biological activity
      of PTH depends on the presence of the amino-terminal portion and in circulation
      is limited to the intact molecule. We describe an immunofluorometric assay for
      the measurement of PTH-(1-84) based on a chicken egg yolk-derived amino-terminal
      antibody bound to microtiter plates by an anti-chicken Ig monoclonal antibody. As
      tracer antibody we employed a Europium-labelled carboxyl-terminal specific
      monoclonal antibody produced from a mouse immunized with hPTH-(53-84)-BSA
      conjugate. The assay included an initial overnight incubation of the sample and
      the solid phase-bound amino-terminal antibody, followed by washing and addition
      of the tracer antibody, and an additional two hours of incubation prior to
      fluorescence reading. The least-detectable dose was in the order of 2.5 pg/ml and
      preliminary studies in 40 normal adults showed values in the range of 4 to 70
      pg/ml; for 12 patients with surgery-proven primary hyperparathyroidism values
      ranged from 109 to 743 pg/ml and for 34 patients with humoral hypercalcemia of
      malignancy from 2.5 to 66 pg/ml. We conclude that this assay, with its increased
      sensitivity and specificity, will be a valuable tool in the study of PTH
      secretion in normal and pathological situations.

PMID- 7640628
TI  - Membrane permeability and sensitivity to lethal heat are affected by lexA and
      recA mutations in Escherichia coli K12.
AB  - Membrane permeability was evaluated in several SOS-deficient strains. Great heat
      sensitivity was observed in all the lexA (Ind-) strains, which was associated to
      an increase in membrane permeability (up to 120% increase above the wild-type
      control), as assayed by the crystal violet (CV) growth inhibition. After
      irradiation with a single UV dose (75 J.m-2 delivered to wild-type and 2 J.m-2 to
      the lexA3 strain), survival was followed by plating cells in both nutrient and
      membrane permeability-selective (nutrient + CV) media and a great lethality due
      to CV was observed in a lexA mutant, which appeared to be about 100 times more
      sensitive to CV compared to its wild-type parent strain. The decreased membrane
      integrity found in the lexA-deficient strains suggests that LexA protein and/or
      LexA-repressed genes may interact with the bacterial membrane, which could be the
      location of SOS events.

PMID- 7640629
TI  - Role of platelets and complement in the clearance of epimastigote forms of
      Trypanosoma cruzi.
AB  - 1. Trypanosoma cruzi epimastigote forms are very rapidly removed from the
      circulation of normal and C5-deficient mice. Depletion of C3 by cobra venom
      factor results in a significant delay in parasite clearance. 2. During parasite
      clearance there is a significant decrease in the number of circulating platelets
      and parasite clearance is considerably delayed in thrombocytopenic animals. 3. In
      vitro incubation of epimastigote forms with normal mouse serum leads to the
      formation of parasite clumps provided that platelets are present. Inactivation of
      factor B or depletion of C3 prevents this phenomenon. 4. When epimastigotes are
      incubated with normal mouse serum they absorb one or more factors required for
      their aggregation with platelets. 5. It is suggested that in mice T. cruzi
      epimastigote forms are removed from circulation by the alternative pathway of
      complement activation and that both C3 and platelets are required for parasite
      clearance.

PMID- 7640630
TI  - A new mutant hairless mouse with lymph node hyperplasia and late onset of
      autoimmune pathology.
AB  - Adult BALB/c male mice were injected with a single dose of ethyl nitroso urea
      (ENU; 250 mg/kg, i.p.) and mated to C57BL/6, DBA/2 and A/J adult females 13 weeks
      later. F1 males were mated with BALB/c females and F2 females were than
      backcrossed to the F1 parents. One BALB/c male mouse thus treated gave origin to
      a mutant presenting hair and skin alterations similar to those of natural
      hairless mutants. The new mutation is located on chromosome 14 near the Es10
      locus, and probably at the same locus for the hairless mutation. Similar to the
      hairless mouse, this new mutant has a normal phenotype at birth and after three
      weeks starts to loose hair which is never replaced. Additionally, the skin
      becomes thickened and wrinkled. One feature that distinguishes this mutant from
      other hairless mice is the peculiar enlargement of its axillary and cervical
      lymph nodes. The new mutant develops membranoproliferative glomerulonephritis
      similar to the rhino mouse, one of the hairless allele mutants already described
      in the literature, but with a much later onset.

PMID- 7640631
TI  - Antiviral activity of interferon gamma in vivo during mouse hepatitis virus
      infection.
AB  - A/J mice became resistant to experimental MHV3 infection after immunization with
      UV-inactivated MHV3 (0% mortality, 0/10). Depletion of interferon (IFN) gamma
      producing CD4+ T lymphocytes with monoclonal antibodies to CD4+ led to
      susceptibility to virus infection (60% of mortality, 6/10). The resistance to
      MHV3 infection of CD4+ T lymphocyte-depleted-A/J mice was restored by treatment
      with 1000 U of IFN gamma on days -1, 0, 1, 2, 3 and 4 (10% of mortality, 1/10).
      The low virus titers observed in resistant mice (controls or CD4+ depleted plus
      IFN gamma treated) were cleared 6 days after infection and the virus titers
      observed among susceptible mice (CD4+ depleted) increased gradually and peaked on
      day 6, when the animals died. Previous data, taken together with the direct
      evidence presented in this paper, provide strong evidence supporting the concept
      of an in vivo antiviral role of IFN gamma through a central action on the
      mechanisms of resistance to MHV3 infection.

PMID- 7640632
TI  - Temporal stability of auditory evoked potentials at different stimulation rates.
AB  - 1. We determined the temporal stability of the N1 and P2 waves of the auditory
      evoked potentials (AEP) for twelve healthy subjects who were tested in two
      sessions separated by 2 to 63 days (mean = 25 days). AEP were obtained at two
      different stimulation rates (1/s and 0.3/s). In addition to wave amplitude and
      latency, the latency difference and the amplitude ratio between the two
      stimulation rates were calculated. 2. Mean amplitudes, latencies, latency
      differences and amplitude ratios were not significantly different between the two
      sessions. Pearson's correlation was significant only for N1 latency at the 1/s
      stimulation rate (r = 0.64, P = 0.02). 3. Factors such as arousal and other
      subjective states of the subjects, personality traits, as well as technical
      aspects of the examinations, may have influenced the temporal stability of the
      AEP.

PMID- 7640633
TI  - Rats do react to stimulus omission.
AB  - 1. The great majority of data supporting the hypothesis of a system capable of
      comparing current sensorial inputs with an internal representation of the
      environment comes from studies about exploratory activity to new stimuli or to
      manipulation of features of a familiar stimulus. On the other hand, these data
      could also be explained simply by arousal constructs. In this context,
      demonstrations of exploratory behavior to the absence of a previously presented
      stimulus (i.e., stimulus omission) would provide stronger support for the idea of
      a comparator. 2. To test the reaction of rats to the absence of a stimulus, rats
      were submitted to 7 exploratory trials in an open-field. In the 1st trial there
      were only two patterns on the apparatus wall. In trials 2-6 a stimulus was
      presented in a designated area of the field. Finally, in the 7th trial this
      stimulus was omitted. Results showed that the animals reacted to the stimulus
      omission by spending more time in the stimulus presentation place during the 7th
      trial than 1) in the 1st trial (also without stimulus), 2) in the 6th trial (last
      trial with a stimulus present), and 3) in 3 neutral sectors of the same size as
      the stimulus presentation place, during the 7th trial. 3. These data indicate
      that rats do react to the absence of a familiar stimulus and provide strong
      support for the existence of a Comparator System since the rats responded to
      "something that wasn't there anymore", a response that could only be due to a
      reaction triggered by a mismatch between internal representation of the
      environment and its present state.

PMID- 7640634
TI  - Distribution of NADPH-diaphorase-positive neurons in the opossum neocortex.
AB  - The distribution of NADPH-diaphorase reactive cells were evaluated both in
      horizontal sections of a flattened cortex and in transversal sections of the
      opossum (Didelphis marsupialis) neocortex. The tangential distribution of labeled
      cells behind the orbitalis fissure was denser in the rostral vs caudal regions
      and in the lateral vs medial regions. Transversal sections revealed that most of
      the positive neurons are in the grey matter, although 1/4 of this population is
      located in the underlying white matter. This pattern of neuronal distribution is
      similar to that previously described in rodents, but quite different from that
      observed in higher mammals such as the cat and primates.

PMID- 7640635
TI  - 5-HT2 receptor blockade by ICI 170,809 does not affect the inhibitory effect of
      the 5-HT1A receptor ligand gepirone on neuroleptic-induced catalepsy.
AB  - Considerable experimental evidence suggests that central dopaminergic (DA)
      transmission is under serotonergic (5-HTergic) modulation. For instance,
      neuroleptic-induced catalepsy (NIC) in rodents, a behavior mainly due to blockade
      of DA receptors in the striatum, can be affected by 5-HTergic manipulation. It
      has been shown that ligands of 5-HT1A receptors (e.g. buspirone, gepirone) reduce
      NIC, while 5-HT2 receptor antagonists (e.g. ritanserin) do not affect this
      phenomenon. However, the role of 5-HT2 receptors in the modulation of NIC is
      still controversial and there is evidence from behavioral models other than NIC
      suggesting the existence of functional interaction between the two subtypes of 5
      HT receptors. The present study was designed to evaluate the effect of ICI
      170,809 (a selective 5-HT2 receptor antagonist) on NIC and to test the possible
      effect of this drug on the anticataleptic effect of gepirone (GP). Male Wistar
      rats weighing 300-350 g were used, and each animal (7 per group, 4 groups) was
      used only once. Catalepsy was induced with haloperidol (H; 1 mg/kg, i.p.) and
      measured at 30-min intervals by means of a bar test. Animals received either ICI
      170,809 (3 mg/kg, i.p.) or 0.9% saline (SL; 0.8 ml, i.p.) 30 min before H. At 110
      min after H, the rats received GP (1 mg/kg, i.p.) or SL (0.8 ml, i.p.). GP
      significantly attenuated NIC (e.g. 739 +/- 106 s vs 1009 +/- 85 s for controls,
      at 150 min after H), while ICI 170,809 did not significantly affect the
      phenomenon (e.g. 978 +/-89 s vs 1009 +/- 85 s for controls, at 150 min after H).
      Pretreatment with ICI 170,809 did not significantly modify the anticataleptic
      effect of GP (e.g. 617 +/- 90 s vs 739 +/- 106 s for SL-pretreated animals, at
      150 min after H). These results confirm reports of the anticataleptic effect of
      GP and the lack of effect of 5-HT2 receptor antagonists on NIC. Moreover, these
      data also suggest the absence of functional interactions between central 5-HT1A
      and 5-HT2 receptors in this model of DA transmission.

PMID- 7640636
TI  - Acquisition and extinction of jumping, two-way shuttle-box and bar press
      avoidance responses in malnourished rats: effects of shock intensity.
AB  - 1. In order to investigate the role of avoidance response and shock intensity in
      avoidance learning in malnourished rats, three avoidance responses (jumping, two
      way shuttle-box and bar press) and three shock intensities (0.4, 0.6 and 1.0 mA)
      were used. Independent groups of 6 rats were used for each response topography
      and shock intensity. 2. Malnourished male Wistar rats were suckled by mothers fed
      a 12% casein diet during the lactation period (0-21 days of age) while the
      mothers of well-nourished controls received a 25% casein diet. After weaning
      (21st day), all animals received a commercial lab chow diet until 70 days of age,
      when the avoidance training started. 3. Malnutrition did not affect the
      acquisition of the avoidance response, but malnourished groups required more
      trials to extinguish jumping and two-way shuttle-box. During the acquisition
      phase all animals learned the jump response faster in comparison to bar press and
      shuttle-box avoidance responses. Both groups in the acquisition phase responded
      faster with 1.0 mA when compared to lower intensities (0.6 and 0.4 mA). The
      malnourished animals showed lower latency of avoidance in the jumping response
      when compared with well-nourished animals. During the extinction phase there was
      a significant effect of diet, response topography and shock intensity in the
      latency to respond and trials to criterion. The increased resistance to
      extinction in malnourished rats was particularly evident with 1.0 mA in the two
      way shuttle-box response. 4. These results suggest that contradictory data
      related to the acquisition of the avoidance response in malnourished animals
      cannot be attributed to response topography or variations in shock intensity.
      Furthermore, our results also indicate that resistance to extinction and latency
      to respond are appropriate parameters for detecting differences between well
      nourished and malnourished animals.

PMID- 7640637
TI  - Behavioral effects of intra-amygdala injections of GABA and 5-HT acting drugs in
      the elevated plus-maze.
AB  - The effect of drugs bilaterally injected into the basolateral/medial nuclei of
      the amygdala on the behavior of male Wistar rats (300-330 g) in the elevated plus
      maze was measured. The benzodiazepine agonist midazolam (MDZ, 20 and 40 nmol, 0.2
      microliters; N = 8-14) significantly increased open-arm exploration (% open-arm
      entries: control = 20.27 +/- 3.71; 40 nmol MDZ = 42.63 +/- 7.16), having thus an
      anxiolytic effect. On the contrary, the non-selective 5-HT2 antagonist ketanserin
      (KET, 1 and 10 nmol, 0.2 microliters; N = 8-11) had an anxiogenic effect (% open
      arm entries: control = 35.61 +/- 6.41; 10 nmol KET = 18.65 +/- 3.89). The 5-HT1A
      full agonist 8-OH-DPAT (2, 4, and 8 nmol, 0.2 microliters; N = 9-12) did not
      significantly change rat behavior in the plus-maze. While the present anxiolytic
      effect of midazolam agrees with results reported by others using punished
      behavior, the effect of the serotonergic drugs does not. Therefore, the effect of
      5-HT acting drugs injected into the amygdala may be determined by the type of
      experimental model of anxiety used.

PMID- 7640638
TI  - Elicitation of retinal spreading depression by barium ions.
AB  - The association of potassium ions with the occurrence and propagation of
      spreading depression is well known. The effects of barium ions, a potassium
      channel blocker, on spreading depression in isolated retina are described. Pulses
      of 1-4 mM BaCl2, when applied to the retina, first induce the reaction, then
      hinder the propagation of the wave which finally stops. The threshold level which
      triggers the reaction is 0.4-0.6 mM BaCl2 but it varies with the composition of
      the superfusing Ringer solution. For example, in retinas superfused with low
      NaCl, or NaCl partially substituted by sodium isethionate, spreading depression
      may be evoked by barium ions at micromolar concentrations, without changing the
      velocity of spreading. The delayed blocking actions observed with higher doses
      may predominantly affect the recovery processes of the wave front, and are
      related to the refractory period of a preceding spreading depression.

PMID- 7640639
TI  - Effects of intrauterine and postnatal protein-calorie malnutrition on metabolic
      adaptations to exercise in young rats.
AB  - The effect of intrauterine and postnatal protein-calorie malnutrition on the
      biochemical ability to perform exercise was investigated in young male rats.
      Malnourished rats were obtained by feeding dams a low-protein (6%) casein-based
      diet prepared in the laboratory during pregnancy and lactation. Control rats
      received an isocaloric diet containing 25% protein. The low-protein diet
      contained additional starch and glucose. At 45 days of age, malnourished rats
      showed lower body weight, serum protein, albumin and glucose levels, hematocrit
      values and heart glycogen content but higher circulating free fatty acids and
      gastrocnemius muscle glycogen than control rats. In response to exercise (50 min
      of swimming), control rats displayed lower heart, gastrocnemius and liver
      glycogen levels whereas malnourished rats showed low glycogen levels only in the
      gastrocnemius muscle. Both control and malnourished rats showed high serum
      glucose and free fatty acid levels after exercise. In conclusion, protein-calorie
      malnutrition improved muscle glycogen storage but this substrate was broken down
      to a greater extent in response to exercise. Malnourished rats were able to
      perform exercise maintaining high blood glucose levels, as observed in control
      rats, perhaps as a consequence of the elevated availability of circulating free
      fatty acids.

PMID- 7640640
TI  - Putative pathways involved in cardiovascular responses evoked from the caudal
      pressor area.
AB  - 1. The caudal pressor area (CPA) is a recently identified site within the
      ventrolateral medulla which is involved in cardiovascular regulation. CPA
      chemical stimulation by L-glutamate produces an increase in arterial blood
      pressure (ABP) while its inhibition by GABA or glycine evokes marked hypotension.
      In the present study, we sought to determine the potential neural pathways
      underlying these responses. 2. In urethane-anesthetized, paralyzed, artificially
      ventilated rats, CPA inhibition by bilateral microinjection of the inhibitory
      amino acid glycine (Gly, 100 nmol 200 nl-1 site-1) produced an average decrease
      of -38 +/- 4.3 mmHg in ABP (N = 6). Ten min after bilateral microinjection of the
      broad-spectrum glutamate antagonist kynurenic acid (KYN, 2 nmol 200 nl-1 site-1)
      into the caudal ventrolateral medulla (CVLM) depressor responses to CPA
      inhibition were virtually abolished (-3 +/- 1.7 mmHg, P < 0.05). Similar
      microinjection of KYN into the rostral ventrolateral medulla (RVLM) or into the
      CPA itself did not modify depressor responses to CPA inhibition by glycine. 3.
      CPA stimulation by bilateral microinjection of the excitatory amino acid L
      glutamate (L-glu, 50 nmol 200 nl-1 site-1) produced an increase in ABP (+43 +/-
      5.4 mmHg, N = 6). Bilateral microinjection of the GABAA antagonist bicuculline
      methiodide (BIC, 200 pmol 200 nl-1 site-1) into the CVLM markedly reduced pressor
      responses to CPA stimulation (+6 +/- 2.7 mmHg, P < 0.05). Similar application of
      BIC into the RVLM or CPA did not modify pressor responses to CPA stimulation by
      glutamic acid.

PMID- 7640641
TI  - Effect of caffeine on the metabolism of rats exercising by swimming.
AB  - Several studies have demonstrated that caffeine improves endurance exercise
      performance but the mechanisms are not fully understood. Possibilities include
      increased free fatty acid (FFA) oxidation with consequent sparing of muscle
      glycogen as well as enhancement of neuromuscular function during exercise. The
      present study was designed to investigate the effects of caffeine on liver and
      muscle glycogen of 3-month old, male Wistar rats (250-300 g) exercising by
      swimming. Caffeine (5 mg/kg) dissolved in saline (CAF) or 0.9% sodium chloride
      (SAL) was administered by oral intubation (1 microliter/g) to fed rats 60 min
      before exercise. The rats (N = 8-10 per group) swam bearing a load corresponding
      to 5% body weight for 30 or 60 min. FFA levels were significantly elevated to
      0.475 +/- 0.10 mEq/l in CAF compared to 0.369 +/- 0.06 mEq/l in SAL rats at the
      beginning of exercise. During exercise, a significant difference in FFA levels
      between CAF and SAL rats was observed at 30 min (0.325 +/- 0.06 vs 0.274 +/- 0.05
      mEq/l) but not at 60 min (0.424 +/- 0.13 vs 0.385 +/- 0.10 mEq/l). Blood glucose
      showed an increase due to caffeine only at the end of exercise (CAF = 142.1 +/-
      27.4 and SAL = 120.2 +/- 12.9 mg/100 ml). No significant difference in liver or
      muscle glycogen was observed in CAF as compared to SAL rats, at rest or during
      exercise. Caffeine increased blood lactate only at the beginning of exercise (CAF
      = 2.13 +/- 0.2 and SAL = 1.78 +/- 0.2 mmol/l). These data indicate that caffeine
      (5 mg/kg) has no glycogen-sparing effect on rats exercising by swimming even
      though the FFA levels of CAF rats were significantly higher at the beginning of
      exercise.

PMID- 7640642
TI  - Vascular actions of insulin in health and disease.
AB  - Insulin has well known metabolic effects. However, depending on the magnitude and
      duration of the insulin stimulus, this hormone can also produce vasodilation and
      vascular smooth muscle growth. The association of hyperinsulinemia with the
      metabolic disorders of obesity and non-insulin-dependent diabetes, as well as
      with the cardiovascular pathologies of hypertension and atherosclerosis, has led
      to suggestions that perhaps elevated insulin levels are causally related to these
      diseases. Alternatively, insulin resistance may develop following an increase in
      skeletal muscle vascular resistance, with or without hypertension, such that a
      reduction in skeletal muscle blood flow leads to an attenuated glucose delivery
      and uptake. These hypotheses are explored in this review by examining the effects
      of insulin on vascular smooth muscle tissue during both acute and prolonged
      exposure. An interaction among hyperinsulinemia, hyperglycemia, and
      hyperlipidemia associated with the insulin resistant state is described whereby
      insulin resistance can be both a cause and a result of elevated vascular
      resistance. The association between blood flow and insulin stimulated glucose
      uptake suggests that therapeutic intervention against the development of skeletal
      muscle vascular resistance should occur early in individuals generally
      predisposed to cardiovascular pathology in order to attenuate, or avoid, insulin
      resistance and its sequelae.

PMID- 7640643
TI  - Stress proteins: the exercise response.
AB  - A class of proteins that undergoes preferential synthesis following a variety of
      stressors has been demonstrated to carry out important cellular functions under
      both stressed and nonstressed conditions. These so-called heat shock (HSP) or
      stress (SP) proteins have been termed "molecular chaperones" and play important
      roles in cellular transportation, assembly/degradation, and cell survival. This
      review provides a basic introduction to the function and regulation of these
      proteins. Emphasis is placed on members of the HSP 70 family of proteins
      (especially HSP 72) and their role in cellular protection, their pattern of
      distribution in skeletal muscle, and changes in their expression following
      exercise and exercise training.

PMID- 7640644
TI  - Caffeine ingestion and performance of a 1,500-metre swim.
AB  - The purpose of this study was to evaluate the potential ergogenic benefit of
      caffeine in the performance of a 1,500-meter swim. Caffeine (6 mg.kg-1) or
      placebo was administered 2-1/2 hrs prior to the swim trial in a double-blind
      crossover design. Caffeine resulted in a significantly lower perceived exertion
      for 100-m warm-up swims. Subjects swam significantly (p < 0.05) faster with
      caffeine (20:58.8 +/- 0:36.4, mean +/- SEM) than without (21:21.8 +/- 0:38).
      Plasma potassium was significantly lower prior to the swim with caffeine, and
      blood glucose was higher after that swim. Caffeine provides an ergogenic benefit
      for a 1,500-meter swim, an event that is completed in less than 25 min. Lower
      plasma potassium concentration prior to exercise and higher blood glucose
      following the trial suggest that electrolyte balance and glucose availability may
      be important aspects of the ergogenic effects of caffeine.

PMID- 7640645
TI  - Central adaptations in aerobic circuit versus walking/jogging trained cardiac
      patients.
AB  - This study was done to determine (a) whether in coronary artery disease (CAD)
      left ventricular (LV) adaptations differed after 6 months of walking/jogging
      (legs-only, LO) versus aerobic circuit training (arms and legs, AL) versus a
      control group, and (b) whether a transfer of fitness to the untrained arms in the
      LO group was related to superior LV adaptations. Peak oxygen uptake for arm and
      leg ergometry and for cycle ergometry using radionuclide cardiac angiography were
      performed before and after training. Leg and arm VO2peak increased significantly
      by 13% in the AL group, and by 13% and 7%, respectively, for the LO group. LV
      function was greater after training for the LO versus the AL group. Improvements
      in systolic and diastolic function and a speculated hypervolemia explain these LV
      adaptations. In CAD patients, walking/jogging produces greater LV function
      improvements versus circuit training, possibly due to differences in the
      exercised muscle mass.

PMID- 7640646
TI  - Kinetics of oxygen uptake for submaximal exercise in hyperoxia, normoxia, and
      hypoxia.
AB  - This study evaluated the dynamic response of VO2 in 6 healthy men at the onset
      and end of submaximal step changes in work rate during a pseudorandom binary
      sequence (PRBS) exercise test and during ramp incremental exercise to exhaustion
      while breathing three different gas mixtures. The fractional concentrations of
      inspired O2 were 0.14, 0.21, and 0.70 for the hypoxic, normoxic, and hyperoxic
      tests, respectively. Both maximal VO2 and work rate was significantly reduced in
      hypoxic tests compared to normoxic and hyperoxic tests. Maximal work rate was
      greater in hyperoxia than in normoxia. Work rate at ventilatory threshold was
      lower in hypoxia than in normoxia and hyperoxia but above the upper limit of
      exercise for the submaximal tests. Hypoxia significantly slowed the response of
      VO2 both at the onset and end of exercise compared to normoxia and hyperoxia.
      Hypoxia also modified the response to PRBS exercise, and again there was no
      difference between normoxia and hyperoxia. These data support the concept that
      VO2 kinetics can be slowed from the normoxic response by a hypoxic gas mixture.

PMID- 7640647
TI  - A study to validate the modified Canadian Aerobic Fitness Test.
AB  - This study evaluated the predictive ability of the modified Canadian Aerobic
      Fitness Test (mCAFT) on an independent sample of subjects and compared it to the
      original Canadian Aerobic Fitness Test (CAFT). Male and female subjects (n =
      154), 15-69 yrs of age, performed the mCAFT and a maximal treadmill test. VO2max
      scores predicted from the mCAFT equation did not differ significantly from those
      measured during the treadmill test, whether the sample was analysed overall or
      categorized by sex, whereas the CAFT (Jette) equation resulted in VO2max scores
      that were significantly lower than either the measured values or those predicted
      using the mCAFT. The strength of the linear relationship between predicted and
      measured VO2max scores is the same for both the mCAFT (r = 0.88) and CAFT (r =
      0.89). However, the mCAFT results in a lower mean square error (37.0 for mCAFT
      vs. 63.3 for CAFT) and thus is an improvement over the CAFT prediction.

PMID- 7640648
TI  - Effects of PNF stretching phases on acute arterial blood pressure.
AB  - This study examined acute systolic (SBP) and diastolic (DBP) blood pressure
      responses within passive and modified proprioceptive neuromuscular facilitation
      (PNF) stretching techniques. Nonhypertensives (N = 60) were assigned to one of
      three treatment groups. Group 1 employed an antagonist passive stretch (APS), 6
      sec maximal voluntary isometric contraction (MVIC) of the antagonist, and
      subsequent APS. Group 2 employed an APS, a 6-sec MVIC of the antagonist,
      submaximal concentric contraction of the agonist, and APS. Group 3 was similar to
      Group 2, with the deletion of an MVIC prior to the concentric contraction. Blood
      pressures were obtained during rest, baseline following passive stretch, and at
      the end of the three phases of the PNF technique. Range of motion (ROM) data were
      collected for baseline and treatment in terminal hip flexion for each group. All
      PNF treatments were effective for increasing ROM. One or two trials of PNF
      improve ROM and avoid increasing SBP, while a third trial increases SBP.

PMID- 7640649
TI  - Isometric cervical extension strength of recreational and experienced cyclists.
AB  - The effect for cyclists of the typical forward sitting position on neck strength
      and its possible relationship to neck pain have not been examined. The purpose of
      this study was to measure the peak isometric cervical extension strength (PICES)
      of both recreational and experienced road cyclists and to compare these values to
      those of noncyclists. Subjects, 45 men between the ages of 18 and 40, were tested
      for voluntary PICES through a 126 degrees range of motion on a MedX cervical
      extension machine. No significant differences were found between the three groups
      in PICES at any angle. When expressed relative to body weight, significant
      differences in PICES were found at 126 degrees between the control group and the
      recreational cyclist group (p < 0.05), and between the control group and the
      experienced cyclist group (p < 0.01), but not at any other angle. Furthermore, no
      significant differences in strength were found between cyclists experiencing neck
      pain and those who did not. These data indicate that the cervical muscles of
      cyclists have not adapted by increasing maximal isometric strength above that of
      noncyclists, and that the neck pain frequently reported may be due to fatigue
      from sustained muscular contractions associated with time spent cycling, rather
      than from muscle weakness.

PMID- 7640650
TI  - Cardiovascular response to orthostatic stress: effects of exercise training
      modality.
AB  - The effects of exercise training posture on cardiovascular and baroreflex
      responses to orthostatic challenge were assessed in highly trained cyclists (CT,
      n = 8) and swimmers (ST, n = 8), and in untrained men (UT, n = 8). CT
      demonstrated the lowest orthostatic tolerance to lower body negative pressure
      (LBNP, 0 to -50 mmHg), with only 3 subjects completing the full LBNP procedures;
      5 UT and all ST completed the testing. During LBNP, stroke volume (SV) decreases
      were similar in CT and ST, but greater than in UT. Mean pulse pressure and
      systemic vascular resistance (SVR) were reduced in CT relative to ST and UT at
      the highest levels of LBNP; the slope of the delta SVR/delta Zo and delta
      SVR/delta SV relationships in CT, used to assess peripheral vascular baroreflex
      function, were attenuated relative to the other groups. There were no between
      group differences in the heart rate response to LBNP. The greater incidence of
      orthostatic intolerance observed in upright-versus supine-trained athletes during
      passive LBNP was linked to attenuated baroreflex control of peripheral vascular
      resistance.

PMID- 7640651
TI  - Polypeptide growth factors in wound healing.

PMID- 7640652
TI  - "Polypeptide growth factors" with special emphasis on wound healing.
      Introduction.

PMID- 7640653
TI  - Transforming growth factor-beta 3.
AB  - Transforming Growth Factor-Beta (TGF-beta) is the general name for a family of
      naturally-occurring polypeptides which have multiple regulatory effects on cell
      proliferation and differentiation. Over the last decade it has become apparent
      that TGF-betas can be produced by most cell types and exert a wide range of
      effects in a context-dependent autocrine, paracrine or endocrine fashion via
      interactions with distinct receptors on the cell surface. This review summarizes
      current knowledge concerning the molecular and cellular biology of TGF-beta 3,
      the most recently described mammalian isoform, and focuses on those physiological
      actions which may lead to clinical applications, particularly in the indication
      areas of wound healing and chemoprotection.

PMID- 7640654
TI  - Transforming growth factor alpha.
AB  - Transforming growth factor alpha (TGF alpha) is a close relative of epidermal
      growth factor (EGF), the first polypeptide mitogen discovered in 1962 (Cohen,
      1962). TGF alpha, like EGF, exerts its effect on cells through binding to the EGF
      Receptor (EGF-R). Here we review the molecular and cell biology of TGF alpha
      before proceeding to describe our own work on signaling molecules induced in
      response to activation of the EGF-R.

PMID- 7640655
TI  - Platelet-derived growth factor.
AB  - Platelet-derived growth factor (PDGF) is a potent activator for cells of
      mesenchymal origin. Two different PDGF chains termed A and B encoded by different
      genes have been identified leading to three different PDGF isoforms, the AA and
      BB homodimers and the AB heterodimer. All three forms have been observed in vivo
      and possess biological activity in vitro with the AA homodimer being the poorest
      cellular mitogen. The availability of highly purified recombinant PDGF isoforms
      was the initial basis for comparative studies in order to specify the different
      spectra of activity of the various PDGF species. This review is particularly
      focused on AB heterodimer as from the standpoint of heterologous gene expression,
      this species is the one with the highest demands concerning expression and
      purification protocols. This explains the fact that, in comparison to PDGF-BB,
      only very limited data on the in vivo application of PDGF-AB are available so
      far.

PMID- 7640656
TI  - Keratinocyte growth factor.
AB  - Keratinocyte growth factor (KGF) is a member of the heparin-binding fibroblast
      growth factor family (FGF-7) with a distinctive pattern of target-cell
      specificity. Studies performed in cell culture suggested that KGF was
      mitogenically active only on epithelial cells, albeit from a variety of tissues.
      In contrast, KGF was produced solely by cells of mesenchymal origin, leading to
      the hypothesis that it might function as a paracrine mediator of mesenchymal
      epithelial communication. Biochemical analysis and molecular cloning established
      that the KGF receptor (KGFR) was a tyrosine kinase isoform encoded by the fgfr-2
      gene. Many detailed investigations of KGF and KGFR expression in whole tissue and
      cell lines largely substantiated the pattern initially perceived in vitro of
      mesenchymal and epithelial distribution, respectively. Moreover, functional
      assays in organ culture and in vivo and studies of KGF regulation by sex steroid
      hormones reinforced the idea that KGF acts predominantly on epithelial cells to
      elicit a variety of responses including proliferation, migration and
      morphogenesis.

PMID- 7640657
TI  - The epidermal growth factor.
AB  - Epidermal growth factor (EGF) is a single polypeptide of 53 amino acid residues
      which is involved in the regulation of cell proliferation. Egf exerts its effects
      in the target cells by binding to the plasma membrane located EGF receptor. The
      EGF receptor is a transmembrane protein tyrosine kinase. Binding of EGF to the
      receptor causes activation of the kinase and subsequently receptor
      autophosphorylation. The autophosphorylation is essential for the interaction of
      the receptor with its substrates. These bind to the receptor by the so-called SH2
      domains. The signal transduction pathways activated by EGF include the
      phosphatidylinositol pathway, leading to activation of protein kinase C and to
      increase in the intracellular Ca2+ concentration, and to the ras pathway leading
      to MAP kinase activation. Recently the cytoplasm has been implicated as playing
      an important role in EGF induced signal transduction. The EGF receptor has been
      demonstrated to be an actin-binding protein. In addition EGF causes a rapid actin
      depolymerisation and the formation of membrane ruffles. In particular these
      membrane ruffles have been shown to act as the first site of signal transduction
      after EGF binding, and thus may be considered as signal transduction structures.
      Finally evidence has been presented suggesting a positive role for EGF and/or the
      receptor in the nucleus.

PMID- 7640658
TI  - Insulin-like growth factors.
AB  - The insulin-like growth factors I and II are single chain polypeptides homologous
      to proinsulin. IGF I and IGF II contribute to cell regulation and stimulate
      protein synthesis via signaling through type 1 receptors which are homologous to
      insulin receptors and activate phosphorylation cascades. IGFs enhance the
      proliferation of chondocytes and the proliferation of their collagen and
      proteoglycan matrix; IGFs stimulate longitudinal (endochondral) bone growth.
      Throughout life, IGFs are constitutively expressed ubiquitous factors which help
      to maintain the survival of differentiated cells, Increased expression is found
      during growth and tissue repair, Six specific binding proteins, IGFBP 1-6, allow
      additional tissue compartment specific control of IGF activity; IGFBP production
      favours storage and IGFBP cleavage leads to activation.

PMID- 7640660
TI  - Factors influencing myofibroblast differentiation during wound healing and
      fibrosis.
AB  - Granulation tissue fibroblasts (myofibroblasts) develop several ultrastructural
      and biochemical features of smooth muscle (SM) cells, including the presence of
      microfilaments bundles and the expression of alpha-SM actin, the actin isoform
      typical of contractile vascular SM cells. Myofibroblasts have been suggested to
      play a role in wound contraction and in retractile phenomena observed during
      fibrotic diseases. When granulation tissue evolves into a scar, myofibroblasts
      containing alpha-SM actin disappear, probably as a result of apoptosis. In
      contrast myofibroblasts expressing alpha-Sm actin persist in excessive scarring
      and in fibrotic conditions. The mechanisms leading to the development of
      myofibroblastic features remain to be investigated. Studies on the factors
      regulating the phenotype of myofibroblasts will be necessary for understanding
      their behavior in vivo, and possibly modifying this behavior during the different
      clinical settings.

PMID- 7640659
TI  - NGF: not just for neurons.
AB  - Nerve growth factor (NFF) is the prototypic member of a family of related
      neurotrophins (Nts). Although originally defined by its actions in the peripheral
      and central nervous systems, recent data indicate the presence of extensive
      interactions between NGF and the endocrine and immune systems steroid hormones
      are able to modulate the neurosomal expression NGF, while functional NGF
      receptors have been detected on cells of the immune system, and increased levels
      of NGF protein are found during the acute phase of diseases with a significant
      inflammatory component. These wider functions are likely to be of concern in any
      attempted therapeutic use of NGF.

PMID- 7640661
TI  - Characterization of two human cAMP-specific phosphodiesterase subtypes expressed
      in baculovirus-infected insect cells.
AB  - Recombinant baculoviruses were constructed to express cDNAs encoding two distinct
      subtypes of human cAMP-specific phosphodiesterase (hPDE4A and hPDE4B). Infection
      of Spodoptera frugiperda insect cells with the appropriate recombinant
      baculoviruses resulted in high level production of biologically-active protein as
      measured by enzymatic activity and immunoblotting using subtype-specific anti
      hPDE4 antisera. Both recombinant proteins showed catalytic activity with a low Km
      (approximately 3 microM) for cAMP (with no cGMP hydrolyzing activity) and were
      inhibited by R-rolipram with apparent Kis of 0.38 and 0.25 microM, respectively.
      The recombinant enzymes also contained saturable, stereoselective and high
      affinity rolipram-binding sites (Kd approximately 2 nM). Thus, insect cell
      derived hPDE4s possess kinetic properties analogous to native enzymes as well as
      to recombinant enzymes produced in yeast.

PMID- 7640662
TI  - Activation of macrophage-like cells by multiple grooved substrata. Topographical
      control of cell behaviour.
AB  - We studied the influence of substrata topography on the behaviour of murine
      P388D1 macrophage cell line. Cells were plated on plain fused silica substrata or
      substrata with microfabricated grooves of varying depth and width. Cell spread
      area, elongation, orientation and F-actin content were measured on plain
      substratum and 6 sets of gratings. The speed and persistence of cell movement
      were also studied. We found that patterned substrata substantially activated cell
      spreading and elongation and significantly increased the persistence and speed of
      cell movement, shallow grooves being more effective than deep ones. The contact
      of cells with micropatterned substrata significantly increased the F-actin
      content in cells. The sensitivity of LPS (lipopolisaccharide) stimulated and
      unstimulated macrophages to topographical cues was also compared.

PMID- 7640663
TI  - The effect of cisplatin and transplatin on the conformation and association of F
      actin.
AB  - The effects of cisplatin and transplatin on the conformation and association of F
      actin were studied by ESR, turbidimetry and CD measurement. The results indicate
      that the major component affecting F-actin secondary conformation is derived from
      their effect on the tertiary or quaternary conformation and association states of
      F-actin. The effect of platinum is seen by the fact that binding of cisplatin
      causes first an increase in molecular size followed by a later decrease. The
      induction time for the association depended on the concentration of cisplatin.
      Transplatin was able to reach the target site more readily, resulting in the
      dissociation of F-actin even at a very low concentration.

PMID- 7640664
TI  - Morphological alterations caused by lithium in various cell lines.
AB  - Lithium is being used for the treatment of mental diseases and for the
      attenuation of muelosuppression during chemotherapy. As during long term lithium
      treatment kidney damage has been reported, we studied morphological alterations
      in cells of kidney origin after exposure to lithium chloride. Above the level of
      4 mmol, lithium has fatal effects in CV1 cells while HeLa cells that are not
      originating from kidneys, tolerate higher lithium concentrations. Cellular
      morphology alters during treatment duration. At early stages, cells become
      flatter on their substrate and upon longer than 4 days treatment begin to detach
      from their substrate and eventually cell death comes in a concentration dependent
      manner. The only morphological alteration observed in a lymphoblastoid cell line
      was a statistically significant cellular swelling.

PMID- 7640665
TI  - Production of human immunodeficiency virus by chronically infected cells grown in
      protein-free medium.
AB  - A human T cell line chronically infected with Human Immunodeficiency Virus (HIV)
      has been adapted to grow in a chemically defined, protein-free medium. Virus
      particles are produced at rates comparable to those of serum-supplemented
      cultures; virus preparations free of undesirable proteins can be produced in
      preparative amounts by simple ultrafiltration procedures and cell culture
      supernatants can be used as such for the preparation of ELISA solid phases. This
      material has been used very conveniently for studies concerning characterization
      of antibodies against HIV-specific proteins, interaction of HIV with complement
      components and inclusion of human cell-derived proteins into virions; we propose
      its use as a powerful tool for the structural as well as functional analysis of
      the virus particle itself.

PMID- 7640666
TI  - Regulation of fibronectin expression by PDGF-BB and IGF-I in cultured rat
      thoracic aortic adventitial fibroblasts.
AB  - Regulation of fibronectin (FN) by Platelet-derived Growth Factor-BB (PDGF-BB) and
      Insulin-like Growth Factor-I (IGF-I) in cultured rat thoracic aortic adventitial
      fibroblasts were examined. PDGF-BB enhances FN mRNA levels in a time and
      concentration-dependent fashion. The effect of IGF-I on PDGF-BB-induced FN levels
      was also examined. There was a larger increase in FN mRNA levels (4-fold) in the
      cells treated with both IGF-I and PDGF-BB than with either IGF-I (2-fold) or PDGF
      BB (2-fold) alone. The effects of PDGF-BB and IGF-I on FN levels were examined.
      There was a larger increase in FN levels (135%) in the cells treated with both
      PDGF-BB and IGF-I than with either PDGF-BB (43%) or IGF-I (45%) alone. Regulation
      of adventitial fibroblast FN may lead to blood vessel diseases and/or
      angiogenesis.

PMID- 7640667
TI  - Early endocytotic steps in elicited macrophages: omega-shaped plasma membrane
      vesicles at their cell surface.
AB  - Fluid-phase and receptor-mediated endocytosis were studied in Freund's adjuvant
      elicited macrophages. These cells were found to bind and internalize
      significantly larger amounts of peroxidase-antiperoxidase (PAP) immune complex
      than resident macrophages. Similarly the rate of the fluid-phase uptake was
      higher in elicited cells. When studying the early steps of endocytotic processes,
      omega-shaped plasma membrane pits (d approximately 90 nm) were found at the
      macrophage cell surface. Although occurring occasionally in resident cells, their
      number was highly increased after elicitation in 30% of the macrophage cell
      population. The different morphology of these cells coincided with a lower
      endocytotic activity and a very strong ecto Ca(2+)-ATPase reaction. The present
      findings indicate that the elicited macrophage population is heterogenous and
      consists of different subclasses.

PMID- 7640668
TI  - Reconstituted human normal breast in nude mice using collagen gel or Matrigel.
AB  - Human breast epithelial cells dissociated from reduction mammoplasty specimens
      were embedded in two commonly used extracellular matrices, type I collagen gel or
      Matrigel, and subsequently transplanted subcutaneously into athymic nude mice.
      Histological sections from both types of recovered gels showed epithelial
      structures arranged as short tubules with some branching as well as preservation
      of epithelial cell polarity. Proliferation was studied in vivo by 5-bromo-2'
      deoxy-uridine labeling followed by immunostaining of sections from recovered
      gels. Human breast epithelia embedded in collagen gel or Matrigel had similar
      proliferative activity. Cholera toxin, 17 beta-estradiol, and epidermal growth
      factor, when tested singly, were growth promoting, and in combination 17,beta
      estradiol and cholera toxin had an additive effect but 17,beta-estradiol and
      epidermal growth factor were not additive. Our model system provides a means to
      study the endocrine control of normal human breast development.

PMID- 7640669
TI  - The involvement of tumor necrosis factor in the multinucleation of macrophages.

PMID- 7640670
TI  - A piperacillin-tazobactam resistant Escherichia coli strain isolated from a
      faecal sample of a healthy volunteer.
AB  - As part of a surveillance programme of the prevalence of antibiotic resistance,
      the faecal bacteria of healthy people (n = 1348) were examined, and the
      antibiotic resistance of the Escherichia coli strains determined. One strain out
      of 142 amoxycillin-resistant isolates, E. coli strain 1662, was also resistant to
      piperacillin-tazobactam but susceptible to amoxycillin-clavulanic acid. The
      piperacillin-tazobactam resistance determinant was transferable to standard E.
      coli strains by conjugation. However, the strain produced a beta-lactamase with
      several characteristics very similar to those of the TEM-1 beta-lactamase, i.e.
      pI of 5.4, an M(r) value of 22,000 and a comparable substrate profile. The enzyme
      was as efficiently inhibited by clavulanic acid and tazobactam as the TEM-1 and
      TEM-2 beta-lactamases but more than the amoxycillin-clavulanic acid-resistant TRC
      1 enzyme. The transferable resistance to piperacillin-tazobactam appears to be
      mediated by a novel resistance mechanism that has previously not been described.

PMID- 7640671
TI  - Evaluation of PCR mediated DNA amplification in non-invasive biological specimens
      for subclinical detection of Mycobacterium leprae.
AB  - DNA from Mycobacterium leprae, present in non-invasive clinical samples from
      leprosy patients, such as nasal secretion and hair bulbs, was submitted to
      amplification by the polymerase chain reaction using a M. leprae-specific
      repetitive sequence as a target. After optimization of sample processing and of
      the PCR conditions, we were able to detect DNA from M. leprae in both types of
      clinical samples, even from paucibacillary leprosy patients. The use of hair
      bulbs and nasal secretion as clinical samples for screening of household contacts
      and for the evaluation of a risk population, or for the follow-up of patients
      under chemotherapy, and monitoring of bacterial load is discussed.

PMID- 7640672
TI  - Biological and serological characterization of Campylobacter jejuni
      lipopolysaccharides with deviating core and lipid A structures.
AB  - Lipopolysaccharides from Campylobacter jejuni were tested for their ability to
      induce toxic lethality in galactosamine-sensitized mice, pyrogenicity in rabbits
      and tumour necrosis factor (TNF) secretion from mouse peritoneal macrophages.
      Compared with those of Salmonella LPS, lethal toxicity was 50% lower,
      pyrogenicity was 30- to 50-fold lower, and ability to induce TNF was 100-fold
      lower. C. jejuni LPS and lipid A exhibited higher phase-transition temperatures
      than those of Salmonella preparations, and thus the former have lower fluidity at
      37 degrees C. This lower fluidity of acyl chains may influence the biological
      activities of C. jejuni LPS, but acyl chain characteristics and diaminoglucose
      replacing glucosamine in the hydrophilic lipid A backbone may also influence the
      supramolecular structure of lipid A, thereby affecting biological activities.
      Although diaminoglucose is present in the backbone of C. jejuni lipid A,
      antigenically the latter resembled classical lipid A of the Enterobacteriaceae
      when tested with anti-lipid A antibodies. Chemical investigations suggested the
      presence of glucuronic acid in an acid labile linkage in the inner core region,
      thus producing a structurally unusual region in C. jejuni LPS.

PMID- 7640673
TI  - Emergence of tetracycline resistance due to a multiple drug resistance plasmid in
      Vibrio cholerae O139.
AB  - Of the 173 clinical strains of Vibrio cholerae O139 isolated from India,
      Bangladesh, and Thailand tested, six strains from India were resistant to
      tetracycline, ampicillin, chloramphenicol, kanamycin, and gentamicin. These six
      strains harbored a self-transmissible plasmid that mediated resistance to
      tetracycline, ampicillin, chloramphenicol, kanamycin, gentamicin,
      sulfamethoxazole, trimethoprim, and O/129. The multiple drug resistance plasmids
      were 200 kb in size and belonged to the incompatibility group C. Although a
      majority of the O139 strains (94.8%) were highly resistant to streptomycin,
      sulfamethoxazole, trimethoprim, and O/129, the tetracycline-susceptible strains
      so far tested were plasmid-negative. The data suggest the existence of two
      distinct multiple antimicrobial agent resistance (MAR) patterns in V. cholerae
      O139.

PMID- 7640674
TI  - Lipid A-associated proteins from periodontopathogenic bacteria induce interleukin
      6 production by human gingival fibroblasts and monocytes.
AB  - The aim of this study was to determine whether lipid A-associated proteins (LAP)
      from two periodontopathogenic species of bacteria were able to stimulate
      interleukin-6 (IL-6) release from human gingival fibroblasts and myelomonocytic
      cells. LAP and lipopolysaccharide (LPS) were extracted from Porphyromonas
      gingivalis and Prevotella intermedia and added to cultures of human gingival
      fibroblasts and mono-mac-6 monocytic cells. Release of IL-6 into the culture
      supernatants was determined by ELISA. LAP and LPS from Por. gingivalis, but not
      from Prev. intermedia, stimulated IL-6 release from both cell types in a dose
      dependent manner although LPS was less potent than LAP in inducing IL-6 release
      from the fibroblasts. IL-6 was detectable in cultures of both cell types
      following stimulation with LAP from Por. gingivalis at a concentration as low as
      10 ng/ml. In response to LAP from Prev. intermedia, IL-6 was produced by mono-mac
      6 cells but not by fibroblasts. Our results show that bacterial cell wall
      components other than LPS can induce IL-6 release from cells of the periodontium
      in vitro. The production of such potent immunomodulatory agents in vivo may
      contribute to the connective tissue breakdown characteristic of chronic
      periodontitis.

PMID- 7640675
TI  - Mouse protection induced by Pseudomonas aeruginosa PAC1R and its defective
      mutants, Salmonella minnesota Re-mutant and Escherichia coli O14.
AB  - Pseudomonas aeruginosa PAC1R and its defective mutants (acetone-killed bacteria),
      Salmonella minnesota Re mutant (acetone-killed bacteria and Re-LPS) and
      Escherichia coli O14 (acetone-killed bacteria and enterobacterial common antigen,
      ECA) were studied in a mouse active protection test. Immunized mice were
      challenged with wild-type P. aeruginosa strains. It was established that P.
      aeruginosa LPS-defective mutants induced cross-immunity against different Fisher
      immunotypes of P. aeruginosa. S. minnesota Re-LPS and ECA gave mice protection
      against P. aeruginosa.

PMID- 7640676
TI  - Vibrio cholerae O139 produces a protease which is indistinguishable from the
      haemagglutinin/protease of Vibrio cholerae O1 and non-O1.
AB  - Haemaglutinin/protease (HA/P) is one of the virulence factors of Vibrio cholerae
      O1 and pathogenic strains of V. cholerae non-O1. In this study, we examined
      protease activity of a new serogroup of Vibrio cholerae recently designated as
      O139 synonym Bengal. The protease activity was produced by all eight isolates of
      V. cholerae O139 from Bangladeshi patients. Purification and partial
      characterization of the protease from V. cholerae O139 demonstrated the purified
      protease (O139-P) was indistinguishable from that previously reported for HA/P of
      V. cholerae non-O1 (NAG-HA/P) and V. cholerae O1 (Vc-HA/P). These results prove
      that V. cholerae O139 produces a protease belonging to HA/P, and suggest that the
      protease is another virulence factor found in newly emerged V. cholerae O139, as
      in V. cholerae O1.

PMID- 7640677
TI  - Staphylococcal enterotoxin B toxicity in BALB/c mice: effect on T-cells, plasma
      cytokine levels and biochemical markers.
AB  - Groups of BALB/c mice were treated with a sub-lethal dose (60 micrograms) of
      staphylococcal enterotoxin B (SEB) intraperitoneally and were sacrificed at 2, 5,
      8, or 10 h post-injection. Organ, blood plasma and lymph node samples from these
      mice were analyzed. Plasma levels of urea, creatinine and alanine
      aminotransferase were significantly raised above normal by 5 h post-injection.
      However, alkaline phosphatase levels showed an erratic increase after toxin
      administration and, after administration of 10-40 microgramS SEB per mouse, were
      consistently at least 30% below normal levels at 24 h post-injection. Weight
      change was also monitored but found to be inconsistent. Lung, spleen and kidney
      samples appeared normal on histopathological examination, but liver samples
      showed minor polymorph infiltration and congestion. TNF-alpha, and IL-1 alpha
      levels in the plasma were raised by 8 h to picogram levels per ml of plasma,
      whereas IFN-gamma and IL-2 were raised by 2 h to nanogram levels per ml of
      plasma. Lymph node cells taken from mice treated with toxin were given a
      secondary stimulation with toxin in vitro. Although the response of the cells was
      lower than normal on assay at four days, a time response curve showed a peak in
      cell responsiveness to secondary stimulation with toxin at three days. These data
      indicate that biochemical markers and cytokine levels are affected by the
      administration of SEB to mice and may be used as indicators of toxicity.

PMID- 7640678
TI  - Biological activity of Burkholderia (Pseudomonas) cepacia lipopolysaccharide.
AB  - Burkholderia cepacia has emerged as an important multiresistant pathogen in
      cystic fibrosis (CF), associated in 20% of colonised patients with a rapid and
      fatal decline in lung function. Although knowledge of B. cepacia epidemiology has
      improved, the mechanisms involved in pathogenesis remain obscure. In this study,
      B. cepacia lipopolysaccharide (LPS) was assessed for endotoxic potential and the
      capacity to induce tumour necrosis factor (TNF). LPS preparations from clinical
      and environmental isolates of B. cepacia and from the closely related species
      Burkholderia gladioli exhibited a higher endotoxic activity and more pronounced
      cytokine response in vitro compared to preparations from the major CF pathogen
      Pseudomonas aeruginosa. This study help to explain the vicious host immune
      response observed during pulmonary exacerbations in CF patients colonised by B.
      cepacia and lead to therapeutic advances in clinical management.

PMID- 7640679
TI  - Evaluating social skills following traumatic brain injury: the BRISS as a
      clinical tool.
AB  - Deficits in social behaviour are a major obstacle to the reintegration into the
      community of traumatically brain-injured (TBI) individuals. Recognition of the
      importance of social skill remediation has highlighted the need for a suitable
      assessment tool. The TBI population presents particular requirements with respect
      to the special nature of deficits which commonly occur as a result of frontal
      lobe impairment. The Behaviorally Referenced Rating System of Intermediate Social
      Skills (the BRISS) has been shown to have good psychometric properties with a TBI
      population. It also provides a measure of particular social skills associated
      with frontal lobe functioning. This study examines the ability of the verbal
      scales of the BRISS to identify social skill deficits at the individual client
      level and to detect significant changes in skills following an intervention
      programme involving five chronic TBI males. In the case of one client, who
      demonstrated significant clinical improvement in social behaviour, the BRISS was
      found to identify specific areas of apparent change. The difficulty of using the
      BRISS as a sole measure of social skills is discussed in the light of relatively
      large pre-intervention within-subject variability which was found with respect to
      some behaviours.

PMID- 7640680
TI  - The disablement experienced by traumatically brain-injured adults living in the
      community.
AB  - The disablement that occurs following traumatic brain injury (TBI) can be
      extensive and severe and consequently has been difficult to report on in a
      comprehensive and thorough manner. We were able to address this difficulty by
      analysing a sub group of data from the Canadian Health and Activity Limitation
      Survey (HALS) using the theoretical framework of disablement developed by the
      World Health Organization, the International Classification of Impairment,
      Disability and Handicap (ICIDH). There were 454 survey respondents (representing
      12,290 in the Canadian population) with disability resulting from a TBI and a
      mean time post-injury of 13 years. Three handicaps identified in the ICIDH were
      the focus of the study: physical independence, work, social integration. The
      prevalence of long term handicap was very high with 66% of the sample reporting
      the need for ongoing assistance with some activities of daily living, 75% not
      working, and 90% reporting some limitations or dissatisfaction with their social
      integration. Multivariate regression analysis was used to investigate the
      determinants of the handicaps. The determinants included: age, gender, level of
      education, living alone, physical environment, and specific disabilities. The
      implications of these findings are discussed in relation to rehabilitation
      issues, the usefulness of the ICIDH as a model to investigate outcomes, and
      directions for future research.

PMID- 7640681
TI  - Establishing standards for the provision of brain injury services.
AB  - Standards and an assessment process were developed to evaluate the quality of
      traumatic brain injury services in New South Wales, Australia, by The Australian
      Council on Healthcare Standards. The set of standards developed addressed the
      provision of rehabilitation services, the management of human and physical
      resources, education, research and quality assurance. An educational peer review
      model was used to conduct on-site assessments of the 14 public sector Brain
      Injury Rehabilitation Program Services. Data collected on the level of compliance
      with the standards showed a high rate of conformity, particularly in the areas of
      patient management, the provision of outpatient and community services, and staff
      development. Feedback from the participating services indicated that the
      assessment process was regarded as a useful tool for identifying problems and
      improving services. The standards and assessment process were shown to be an
      effective tool for evaluating the quality of services provided, and repeat
      assessments will enable the ongoing development of services to be monitored.

PMID- 7640682
TI  - Persistent vegetative state: which sensory-motor variables should the
      physiotherapist measure?
AB  - This study used a modified Delphi technique to establish a list of core items
      which should be included in the measurement, by the physical therapist, of
      sensory-motor capacities of persons in a persistent vegetative state. Twenty
      eight physical therapists with a mean of 5.9 years of experience working with
      this clientele participated in the study and identified 105 items as being
      important in the evaluation of the PVS patient (Round I). The study planning
      committee reduced these to 20 categories and asked the therapists to rate each
      category of items (a 5-point scale) as to it's importance (Round II).
      Physiotherapists identified 14 variables as being 'extremely' or 'very important'
      to include in such an evaluation. These included: tonus, voluntary movement on
      request, postural reactions, passive range of motion, tolerance to
      verticalization and postural status. These results are being used to develop a
      quantitative assessment instrument to be used by the physical therapist working
      with the PVS patient.

PMID- 7640683
TI  - Extent of cognitive decline in traumatic brain injury based on estimates of
      premorbid intelligence.
AB  - Global cognitive impairment following traumatic brain injury (TBI) is common,
      with some abilities more significantly affected than others. However, due to
      difficulties in estimating premorbid intelligence, there has been no systematic
      evaluation of the extent of decline in different cognitive abilities following
      TBI. Recent studies indicate that the Wide Range Achievement Test-Revised (WRAT
      R) Reading subtest is an accurate estimate of premorbid intelligence, suggesting
      that post-TBI cognitive test scores can be compared to the WRAT-R to estimate the
      extent of decline that occurs in specific cognitive abilities. The current study
      estimated the extent of deficit in intelligence, memory, attention, speed of
      processing, and cognitive flexibility for 97 outpatients with TBI. Extent of
      decline was calculated by subtracting WRAT-R z-scores from cognitive test z
      scores to determine a z-difference score (ZDiff) for each cognitive ability. The
      results suggest that intelligence is least declined following TBI (WAIS-R 3-4
      point decline; VIQ ZDiff = -0.23: FIQ ZDiff = -0.27), followed by attention (WMS
      R 5-point decline; ZDiff = -0.31), memory (WMS-R 6-9-point decline; Verbal Memory
      ZDiff = -0.41; General Memory ZDiff = -0.51; Delay Memory ZDiff = -0.57), speed
      of processing (Trails A 15-16 second decline; ZDiff = -1.90) and cognitive
      flexibility (Trails B 35-52 second decline; ZDiff = -2.65). Implications for
      provision of feedback to individuals with TBI and their families are discussed.

PMID- 7640684
TI  - The impact of brain injury on family functioning: implications for subacute
      rehabilitation programmes.
AB  - An attempt was made to institute a monthly family treatment programme at a medium
      to-long-term subacute care rehabilitation facility. Patients were generally
      between the ages of 20 and 70, and time since onset of injury ranged from
      approximately 1 to 15 years. In addition, these patients were markedly impaired
      and often exhibited periods of severe behavioural dyscontrol. Family involvement
      was idiopathic and unstructured at the beginning of the project. In contrast, the
      literature is replete with both empirically based studies and theoretical papers
      that attest to the critical importance of working with brain injury survivors'
      families throughout the acute and subacute phases of recovery [1, 2]. Clearly,
      sequelae of moderate to severe brain injury can be as pervasive and severe for
      families as for patients themselves [3, 12]. Therefore, the department of
      psychology introduced a structured family treatment programme in the hope of
      facilitating effective communication between family members, decreasing displaced
      incidences of behavioural dyscontrol, and allowing patients to concentrate on and
      successfully achieve their treatment goals.

PMID- 7640685
TI  - Performance data for traumatic brain-injured subjects on the Gordon Diagnostic
      System (GDS) tests of attention.
AB  - Thirty adults with traumatic brain injury (TBI) (20 males and 10 females, mean
      age 40 years) and a non-injured control group (12 males and 13 females, mean age
      41 years) were tested on 16 tests of attention including three tasks of the
      Gordon Diagnostic System (GDS), a relatively new set of attention tasks. No
      differences between groups were found on age or education. Both groups had
      estimated IQs in the average range. Performance data for the GDS are presented
      for the TBI and CON groups. Mild to moderate deficits of attention were seen in
      the TBI group relative to controls on the Vigilance and Distractibility tasks. No
      differences between groups were seen on the Standard Delay groups. Person product
      moment correlations suggested different patterns of relationships between the GDS
      tasks and other tests of attention for the TBI and CON groups. These results
      support the utility of the Vigilance and Distractibility tasks for assessment of
      attention in a mild to moderately injured population.

PMID- 7640686
TI  - Mild traumatic brain injury does not produce post-traumatic stress disorder.
AB  - It has been widely assumed that patients who sustain mild traumatic brain injury
      (MTBI) or post-concussive syndrome develop post-traumatic stress disorder (PTSD)
      in response to their cognitive difficulties, diminished coping skills, or other
      losses. This study examined 70 patients who had previously been diagnosed as
      having either PTSD or MTBI. Each patient was asked to provide a highly detailed
      chronological history of the events which preceded, followed, and occurred during
      the traumatic event, to indicate whether they were rendered unconscious or had
      amnesia for the event, and to describe the various symptoms they developed. All
      (100.0%) of the PTSD patients were able to provide a highly detailed and
      emotionally charged recollection of the events which occurred within 15 minutes
      of the traumatic event in comparison to none (0.0%) of the MTBI patients. None of
      the MTBI patients reported symptoms such as intrusive recollections of the
      traumatic event, nightmares, hypervigilance, phobic or startle reactions, or
      became upset when they were asked to describe the traumatic event or were exposed
      to stimuli associated with it. These data suggest that PTSD and MTBI are two
      mutually exclusive disorders, and that it is highly unlikely that MTBI patients
      develop PTSD symptoms. Furthermore, these findings suggest that clinicians should
      exercise considerable caution in ruling out PTSD prior to making the diagnosis of
      MTBI.

PMID- 7640687
TI  - Deep venous thrombosis in the spastic upper limb.
AB  - Deep venous thrombosis (DVT) of the upper extremity (UE) is an uncommon
      diagnosis, whereas DVT of the lower extremity is a well-known cause of morbidity
      and mortality in the rehabilitation patient. Patients with UE DVT secondary to
      venous stasis, vessel wall abnormalities, hypercoagulability, venous
      instrumentation and cancer have been previously reported in the literature. To
      our knowledge no case of DVT in a spastic upper extremity has been noted. A case
      report of a patient with UE DVT in a spastic extremity secondary to traumatic
      brain injury is presented, with a discussion of the aetiology, diagnosis and
      management of this disorder.

PMID- 7640689
TI  - Publications from the Caribbean in the health sciences.
AB  - The investigation reported here examined scientific publications from Barbados,
      Jamaica, and Trinidad and Tobago over the period 1976-1990. Its purpose was to
      provide new information about Caribbean research in the health field through
      assessment of published works. To this end a broad array of journal subject
      categories was examined using SCISEARCH, an international index of medical and
      scientific literature. In all, 1,712 titles (articles, editorials, reviews,
      letters, meeting abstracts, and notes) were selected for analysis. This analysis
      indicated that Jamaica accounted for about three-quarters of the titles and that
      there had been a steady increase in the number of titles published over the study
      period that was most marked in Barbados. Most of the principal authors were
      affiliated with the University of the West Indies, and nearly one-third of the
      titles were published in the West Indian Medical Journal, the sole publication
      from the three study countries that SCISEARCH listed. Most of the subjects
      covered fell within the area of "general medicine" rather than experimental
      medicine or public health. However, of the 383 titles dealing with experimental
      medicine, nearly all (331) originated in Jamaica. In contrast, less than half of
      the 262 titles in the public health field came from Jamaica, a relatively large
      number (106) originating in Trinidad and Tobago. Most of the 1,712 titles (63.8%)
      dealt with topics outside the priority areas identified by the Caribbean
      Ministers of Health as part of the Caribbean Cooperation in Health (CCH)
      Initiative.

PMID- 7640688
TI  - Classification of the spectrum of mild traumatic brain injury.
AB  - Mild traumatic brain injury (TBI) is a very common injury, resulting in immediate
      and possible long-term symptoms. The accurate and consistent definition of mild
      TBI is important in the initial and rehabilitation management of the injury, and
      in research concerning mild TBI. A definition of mild TBI has been developed by
      the Head Injury Interdisciplinary Special Interest Group of the American Congress
      of Rehabilitation Medicine. Within the spectrum of injury severity in mild TBI
      there are several classification systems, primarily used in management of acute
      mild TBI, that breakdown mild TBI into grades of injury severity. These are based
      upon the presence or absence of mental status changes, amnesia, loss of
      consciousness, anatomical lesion or neurological deficit.

PMID- 7640690
TI  - Neonatal tetanus mortality in Veracruz, Mexico, 1989.
AB  - This article describes a survey conducted in the State of Veracruz, Mexico, to
      estimate neonatal tetanus (NNT) mortality. The survey, which entailed visits to
      72,720 households, collected data on 8,401 live births and 209 infant deaths
      occurring between April 1988 and May 1989. Twenty-six of the 209 fatalities
      conformed to a WHO standard case definition of death from neonatal tetanus. The
      estimated neonatal tetanus mortality was thus 3.1 deaths per 1,000 live births
      (95% confidence limits = 1.7, 4.5). Comparison of this rate to reported figures
      suggests that for every NNT death recorded in Veracruz during the study period,
      as many as 50 others went unreported. A case-control study nested within the
      survey was conducted to assess preventable NNT risk factors. Limited information
      on 13 NNT deaths and 217 controls showed an increased risk for neonates who were
      delivered at home and whose parents' ethnic background was Mexican Indian. Five
      of the 13 fatalities had their umbilical cords cut with a domestic or traditional
      cutting tool such as a reed cane, as compared to none of the 217 controls. The
      observed vaccine efficacy of 2+ doses of tetanus toxoid was 70% (95% confidence
      limits = 52, 100). Both the mothers of neonates who died of NNT and their
      controls missed an average of five opportunities to receive tetanus toxoid. These
      findings underscore the need to launch a perinatal health program serving
      Mexico's high-risk populations.

PMID- 7640691
TI  - Parasitic infections associated with HIV/AIDS in the Caribbean.
AB  - This review article seeks to highlight the significance for the Caribbean of
      major parasitic infections associated with AIDS, encourage awareness of these
      opportunistic parasites, and promote familiarity with appropriate diagnostic
      techniques and their clinical relevance. Specific agents considered include
      Pneumocystis carinii; Toxoplasma gondii; the enteric coccidians Cryptosporidium
      spp., Isospora belli, and Cyclospora cayetanensis; the hemoflagellates Leishmania
      spp. and Trypanosoma cruzi; the fungi Histoplasma capsulatum and Cryptococcus
      neoformans; the nematode Strongyloides stercoralis; and the mite Sarcoptes
      scabiei. These disease agents can be divided into two groups, the immune
      regulated "endogenous" parasites (the protozoans P. carinii and T. gondii, and
      possibly the roundworm S. stercoralis) and intracellular parasites (including the
      enteric coccidia, hemoflagellates, and fungi). Both in the Caribbean and
      elsewhere, the endogenous parasites (particularly P. carinii and T. gondii) are
      the most troublesome for AIDS patients, partly because they are likely to be
      transmitted and establish a benign immunoregulated presence early in the
      subject's life. Indeed, health management programs for AIDS patients often
      routinely include P. carinii prophylaxis, since nearly all such patients who
      survive long enough are expected to experience an episode of acute P. carinii
      infection. In contrast, there is no known epidemiologic association between AIDS
      and strongyloidiasis in the Caribbean, and the prevalence there of potentially
      opportunistic hemoflagellates such as Leishmania spp. and Trypanosoma cruzi is
      relatively low.

PMID- 7640692
TI  - Infant bottle propping among a low-income urban population in Mexico.
AB  - The prevalence of bottle propping (permitting an infant to drink from a bottle
      unattended) and the determinants of this practice at 1 week and 4 months of life
      were studied in a selected sample of urban women in Hermosillo, Mexico. The
      sample (n = 165) consisted of mothers planning to breast-feed who gave birth to
      healthy infants at one of two public hospitals. Data were obtained by
      interviewing women shortly before they were discharged from the hospital and at
      about 1 week and 4 months postpartum. Among those mothers giving liquid breast
      milk substitutes to their infants, the percentage practicing bottle propping
      increased from 27% at 1 week (n = 20/74) to 67% at 4 months (n = 87/130). Women
      who practiced bottle propping at 1 week were significantly more likely to
      continue this practice at 4 months. Bottle propping was significantly more
      common, both at 1 week and 4 months, among women who had completely weaned their
      infants than among those who were still combining breast and formula feeding.
      Multivariate logistic regression indicated that 1-week risk factors for bottle
      propping were low socioeconomic status, being a multiparous single mother, and
      being a young mother (< or = 18 years old) with a female infant, while 4-month
      risk factors were complete weaning, delivery in a "nursery" (versus a "rooming
      in") hospital, and lack of support by the mother's partner for breast-feeding.
      While the possible health risks associated with early bottle propping have not
      been well defined, the extent of the practice observed in this study suggests
      that such risks deserve further investigation.

PMID- 7640693
TI  - Dengue in French Guiana, 1965-1993.
AB  - While it seems likely that dengue fever (DF) has existed in French Guiana for at
      least one century, data on outbreaks are sketchy before temporary eradication of
      the dengue vector mosquito Aedes aegypti and its reestablishment in the early
      1960s. Dengue cases were serologically confirmed for the first time in 1965, and
      since then dengue epidemics have occurred at two to six year intervals, the most
      important occurring in 1968-1969, 1970, 1972, 1976, 1982, 1986, and 1992. Three
      of the four dengue virus serotypes (dengue-1, dengue-2, and dengue-4) have been
      implicated in these outbreaks. During the 1992 epidemic, which appears to have
      begun in 1991 and extended into 1993, cases of dengue hemorrhagic fever (DHF)
      were confirmed for the first time. In all, at least 40 DHF cases and several
      deaths were associated with this epidemic. This development has raised
      considerable concern about the public health threat posed by DHF in French
      Guiana. Such concern is only heightened by the fact that while vector control is
      the sole means of preventing or combating dengue outbreaks, it has proved
      difficult to maintain vector populations at low levels with the control measures
      currently employed.

PMID- 7640695
TI  - Prevention and elimination of rabies in Latin America: meeting of national
      program directors.

PMID- 7640694
TI  - The management information system and change processes in health systems.
AB  - This report describes a management information system (MIS) designed by PAHO's
      Health Systems and Services Division in collaboration with technical experts from
      a number of different countries. This MIS, a methodology currently used at the
      institutional or national level in more than 21 countries of the Americas, is a
      strategic and practical instrument that is easy to apply, interpret, and use, and
      whose purpose is to facilitate fundamental changes in health management. Based on
      the management concept that inputs, processes, and outputs are quantifiable, the
      MIS places special emphasis on health system productivity, an essential condition
      for achieving health coverage that is both adequate and equitable.

PMID- 7640696
TI  - Humanitarian assistance in Haiti.

PMID- 7640697
TI  - World Health Day 1995 focuses on immunization.

PMID- 7640698
TI  - Isolation of dengue type 3 virus prompts concern and action.

PMID- 7640699
TI  - Bolivian hemorrhagic fever reappears.

PMID- 7640700
TI  - Rising sex, drugs and violence hurt U.S. teens' health.

PMID- 7640701
TI  - Elevator etiquette.

PMID- 7640702
TI  - Gauging your system's performance.

PMID- 7640703
TI  - Boost in drug psychotherapy.

PMID- 7640704
TI  - Treating cancer.

PMID- 7640705
TI  - Reality check.
AB  - Rather than take part in realigning the way health care is delivered, organized
      nursing has opted to stonewall change. But if nurses proactively participate in
      the process, they can be in on the decisions that will shape our new health care
      structure.

PMID- 7640706
TI  - A man for the people. Interview by Kevin Lumsdon.
AB  - The new chairman-elect of the American Hospital Association believes passionately
      in the social mission of health care. His 25-year career in health care has
      taught the CEO of PMH Health Resources Inc. exactly what the terms "community"
      and "commitment" mean, and given him a clear notion of the challenges facing the
      AHA as it strives to meet the needs of health care executives in the coming
      years.

PMID- 7640707
TI  - Can purchasing alliances adapt?
AB  - Hospital purchasing alliances' niche used to be buying products in bulk and
      passing on the savings to their members. Since multihospital networks often have
      enough economic clout to cut their own deals, alliances need to be more than go
      betweens.

PMID- 7640708
TI  - Fit to be cared for. Crozer-Keystone has a new design for health care.

PMID- 7640709
TI  - Choose your tomorrow.
AB  - In this climate of rapid change, hospitals need to be ready for anything.
      Scenario-based planning, a tool other industries swear by, could help. The
      process involves coming up with a handful of likely contingencies and then
      inventing strategies to react to those potential tomorrows.

PMID- 7640710
TI  - Future non-shock. An AHA (American Hospital Association) event looks ahead.

PMID- 7640711
TI  - Rehabilitation. Learning on Easy Street.

PMID- 7640712
TI  - Community. Give a CARE (Creating an Attitude for a Responsive Environment).

PMID- 7640713
TI  - Training. Managed care 101.

PMID- 7640714
TI  - Waiting room. Tuning out TV trash.

PMID- 7640715
TI  - Ten tips: an ambulatory care primer.

PMID- 7640716
TI  - Mergers. Why tie the knot?

PMID- 7640717
TI  - HospitalPulse ... March saw admissions still on the rise.

PMID- 7640718
TI  - Congress is driving, but we've got the map.

PMID- 7640719
TI  - Anesthesia mishap: who's in charge.

PMID- 7640720
TI  - Dysphagia: evaluation and treatment.
AB  - Normal swallowing consists of a set of physiologic behaviors which result in
      food, liquid or other substances moving safely and efficiently from the mouth to
      the stomach. Dysphagic patients may have difficulty with any one or more of the
      anatomic or physiologic components of the oral, pharyngeal or esophageal stages
      of the swallow. Evaluation of the dysphagic patient should identify the anatomic
      or physiologic abnormalities characterizing the patient's swallow and include
      introduction and assessment of the efficacy of treatment strategies. Treatment
      may involve compensatory management, such as postural changes or enhancing
      sensory input, or active muscle exercise with or without the introduction of
      food. Speech-language pathologists have taken the lead in research on normal
      swallow and evaluation and treatment strategies for dysphagia.

PMID- 7640721
TI  - Augmentative and alternative communication: past, present and future.
AB  - Augmentative and alternative communication (AAC) for severely communicationally
      impaired people has developed with input from clinicians, users and their
      families, manufacturers, and researchers. A number of users of AAC are now
      internationally known figures. The increasing power and decreasing size and cost
      of computer-based technology continually offer new possibilities for improving
      AAC systems. It is important that such systems take into account the real needs
      of users, and the complex nature of human communication. It is also important to
      realize that AAC development is not a technical question alone. Many effective
      techniques do not involve sophisticated technology, and the provision of AAC for
      those who need it is often a matter of policy implementation rather than
      technical development. AAC is a new and exciting field. It is one which offers
      many challenges to all those associated with it. The benefits, however, are
      enormous. In order to advance the field increased international co-operation is
      required with respect to interventions, technologies, policies and services.

PMID- 7640722
TI  - Determinants of treatment choice for menopausal hot flushes: hormonal versus
      psychological versus no treatment.
AB  - Sixty-one women, reporting hot flushes once a week or more frequently, completed
      questionnaires eliciting information about demographic details, health, mood and
      health beliefs. They were interviewed and asked to choose between no treatment,
      hormone treatment (HRT), psychological treatment (cognitive-relaxation therapy
      (CRT) and no preference for either CRT or HRT. Seventy-five per cent wanted
      treatment, with approximately 40% of these women preferring HRT and 60% CRT.
      Women who wanted treatment for hot flushes were significantly more anxious, coped
      less well with stress, had lower internal locus of control scores and lower self
      esteem, compared with those not seeking treatment. Hot flush frequency was the
      same for both groups, but those wanting treatment viewed flushes as being more
      problematic. Few differences emerged between those preferring hormonal or
      psychological treatment. However, particular reasons were given based upon past
      experience, views about medication and practical considerations. This study
      highlights the need for the development of alternative treatment regimens for
      women seeking help for menopausal problems.

PMID- 7640723
TI  - Coping style and preterm labor.
AB  - Psychometric tests (State-Trait Anxiety Index and Utrechtse Coping Lijst) were
      administered to 23 primigravidae hospitalized for preterm labor and to 22
      controls in order to investigate whether women with and without preterm labor
      present a different coping style or (in) effectiveness of this coping and whether
      the coping style predicts duration of hospitalization and gestational age at
      delivery. No significant differences in trait anxiety nor in coping style were
      found between women with and women without preterm labor. However, within the
      group of women with preterm labor, coping mechanisms are important predictors of
      course and outcome of the preterm contractions. Palliative coping and social
      support seeking are protective mechanisms while active coping has an adverse
      effect upon outcome: an older gestational age at the moment of delivery is for
      44% predicted by a higher social support seeking and a lower active coping.

PMID- 7640724
TI  - Psychosomatic obstetrics in the countries of central and Eastern Europe.
AB  - Womens' experiences of pregnancy and birth in the countries of Central and
      Eastern Europe are explored in this paper. Most of these countries are in
      transition from a totalitarian system of government to that of democracy. The
      implications of this re-orientation are many. Not least of all are the changes
      taking place in health care systems in general, as well as in maternal-child
      health care in particular. This paper reviews the current state of some perinatal
      care systems in these countries. It is not a research paper: it reflects
      observations and recommendations arising from humanitarian aid service in these
      countries and from available literature.

PMID- 7640725
TI  - Patterns of psychological distress in infertile couples.
AB  - The present investigation used a sample of 104 infertile couples to examine
      patterns of distress among couples. Couples were separated on the basis of which
      spouse(s) experienced distress: Both non-distressed (33%), Male distressed (18%),
      Female distressed (22%), Both distressed (27%). Most couples tended to exhibit
      parallel functioning (60%) with both spouses functioning at similar levels, while
      the remainder experienced complementary patterns with one distressed and the
      other not. Of particular note is the finding that a substantial number of
      infertile couples (18%) have a distressed husband paired with a non-distressed
      wife, which is counter to the general assumption that infertility is more
      distressing to women than to men. The Both non-distressed couples had the least
      overall psychological distress, with higher estimates of marital satisfaction.
      They and the couples from the Male distressed group had been in the treatment
      process less time and were drawn primarily from infertility clinics. The Female
      distressed group and Both distressed group had been in treatment for the longest
      time and were primarily recruited through RESOLVE, Inc. (a national non-profit
      organization for infertile people). These data illustrate the importance of
      considering the contextual pattern of distress in couples when considering women
      or men being treated for infertility.

PMID- 7640726
TI  - Two cases of premenstrual sleep terrors and injurious sleep-walking.
AB  - There are currently three recognized menstrual-related sleep disorders:
      premenstrual insomnia, menopausal insomnia and premenstrual hypersomnia. Another
      category, premenstrual parasomnia (sleep behavior disorder), is now suggested.
      Case 1, a 17-year-old female, presented with a 6-year history of exclusively
      premenstrual sleep terrors and injurious sleep-walking that began 1 year after
      menarche. During the four nights preceding each menses, she would scream and run
      from her bed. There was no history of premenstrual syndrome. Neurological
      evaluations had been unrevealing, apart from mild mental retardation and
      attention deficit disorder; there was no psychiatric history. Polysomnography 3
      days before the onset of menses confirmed the diagnosis of sleep-walking.
      Pharmacotherapies were not satisfactory, but self-hypnosis at bedtime was rapidly
      effective with benefit sustained at 2.5-year follow-up. Case 2, a 46-year-old
      woman without psychiatric disorder, presented with a 5-year history of sleep
      terrors and injurious sleep-walking that initially was not menstrually related,
      but beginning 8 months prior to referral, she developed an exclusively
      premenstrual parasomnia that, after polysomnography, was partially controlled
      with bedtime self-hypnosis and clonazepam, 0.25 mg.

PMID- 7640727
TI  - Focal vulvitis: a psychosexual problem for which surgery is not the answer.
AB  - In the last decade focal vulvitis has been identified as a distinct syndrome,
      characterized by unexplained burning vulvar pain and superficial dyspareunia. A
      'Woodruff perineoplasty' has been recommended as a treatment method. A research
      project was conducted, investigating the long-term results of surgical treatment
      and the etiology of focal vulvitis. Results showed that the great majority of
      women continued to suffer from focal vulvitis after the operation, which leads to
      the conclusion that the procedure should be abandoned. Retrospective data
      revealed several immediate causes of mechanical and chemical irritation of the
      vulva. All women exhibited 'inadequate sexual behavior': having intercourse
      without a sufficient amount of lubrication and/or in the presence of hypertonia
      of the pelvic floor. Psychosexual processes were further characterized by
      deterioration of sexual and general well-being, resulting in lack of libido and
      depression, which contributed considerably to the problem. An integrated approach
      to treatment is recommended, which incorporates protection of the vulvar skin,
      relaxation of pelvic muscles and sexological treatment of the psychosexual and
      relational aspects.

PMID- 7640728
TI  - Expectations and knowledge of pelvic examinations in a random sample of Danish
      teenagers.
AB  - The purpose of the study was to describe teenagers' expectations and knowledge of
      the pelvic examination (PE). The study was carried out as a cross-sectional
      postal questionnaire study. A total of 1500 women, aged 17 years, were selected
      at random from all Danish women of that age. The response rate was 76%, and 551
      of these 1112 teenagers had experienced their first PE. Among the teenagers who
      had not had a PE, 48% thought the examination would be painful, 29% feared that
      the doctor would discover abnormal anatomy, 67% felt they would be embarrassed by
      exposing their genitals and 23% expected to be indisposed for the rest of the
      examination day. Among the teenagers who had not experienced a PE, only 17% felt
      that they had sufficient knowledge of the examination, compared to 68% in the
      group who had already experienced an examination. In the group who had not
      experienced a PE 33% knew what the doctor was able to inspect during the
      instrumental part of the examination, compared to 55% in the other group with
      experience. It is concluded that a considerable proportion of teenagers have
      negative expectations of the PE, and increased effort to improve teenagers'
      expectations and knowledge of the PE may be recommended.

PMID- 7640729
TI  - [Quinolones in pediatrics].

PMID- 7640730
TI  - [Ear atresia. From principles to a particular case].

PMID- 7640731
TI  - [Cord blood grafts: perspectives and problems].

PMID- 7640732
TI  - [Eradication of asymptomatic carrier state of non-typhoid Salmonella with two
      doses of pefloxacin].
AB  - BACKGROUND: The carrier state of Salmonella may represent a source of
      contamination for other people. Its treatment is unsatisfactory so that a carrier
      may shed organisms for numerous months. POPULATION AND METHODS: From 1990 to
      1993, 17 children aged 1.5 months to 8 years were seen because they were
      asymptomatic carriers of non-typhoid Salmonella, confirmed by three successive
      stool cultures. All had presented earlier acute severe infection having required
      treatment with amoxicillin (13 cases) and ceftriaxone or cefotaxime (four cases).
      They were given one dose of pefloxacin, 12 mg/kg, 4 to 8 weeks after the initial
      episode. This unique dose was administered again 4 days later. Stool cultures
      were performed before the first administration and 10, 30, 45 and 60 days after,
      with a last control 3 to 4 months later. RESULTS: Eradication of the Salmonella
      was obtained by the 10th day in 13 patients and within the 3 following weeks in 2
      others. Those children who excreted a few number of organisms were early
      eradicated while the 2 patients who did not respond to pefloxacin shed larger
      number of bacteria. There was no side-effects of treatment. CONCLUSION: A short
      treatment with pefloxacin appears to be effective and safe in eradicating the
      carrier state when stool excretion of Salmonella is moderate.

PMID- 7640733
TI  - [Esophageal dilatation in pediatrics: study of 33 patients].
AB  - BACKGROUND: Esophageal dilatation is usually regarded as an effective therapy in
      a majority of esophageal stenosis in childhood. However, the limited number of
      pediatric data does not allow definite conclusions on indications and
      complications of such a procedure. PATIENTS AND METHODS: The files of 33 children
      whose esophageal stenosis had been treated by dilatation by the same operator
      between 1983 and 1992 were retrospectively reviewed. The structure mechanisms
      were: group 1: repair of esophageal atresia (n = 9), group 2: caustic esophagitis
      (n = 6), group 3: peptic esophagitis (n = 12), group 4: unclassified structures
      (congenital esophageal stenosis, achalasia) (n = 6). The dilatations were
      performed under general anesthesia, and the dilatator guide was introduced under
      endoscopic control. Two methods were used: Savary esophageal bougies and balloon
      dilatation. A thoracic X-ray was systematically performed after each dilatation.
      RESULTS: One hundred and fourteen dilatations (3.5 dilatations/child) were
      performed (range: 1-32 dilatations). Twenty-five of the 33 children (76%) were
      dramatically improved after mechanical dilatation. Esophageal dilatation was
      unsuccessful in the eight other patients, seven of them requiring a surgical
      repair. Complications occurred in 3.4% of the dilatations: one esophageal
      perforation, one pneumomediastinum and two cardiac arrests (one of vagal origin
      and 1 after accidental extubation). All patients survived. Efficacy, duration of
      dilatation and complication rates were not similar in the four groups.
      CONCLUSIONS: Esophageal dilatation should be considered as a simple and effective
      procedure when strict security rules are respected by a trained operator.

PMID- 7640734
TI  - [Judicial and administrative consequences of reporting of adolescents in danger].
AB  - Adolescent victims of abuse or neglect are regularly reported to social agencies
      and legal authorities. However, decisions following reports often remain unknown,
      leaving the question of the reporting's relevance open. POPULATION AND METHODS-
      Forty-one consecutive written reports sent to child protective services were
      reviewed, and their content analysed. These services were then contacted by
      telephone, in order to gather information on outcome. RESULTS--Forty-one reports
      concerned 40 adolescents (32 girls, 8 boys); 36 of whom had been admitted to our
      adolescent medicine ward. The most common reason for admission was a suicide
      attempt (20 cases). Thirty-nine reports were destined to legal authorities, while
      two to social agencies. The reason for reporting was physical or sexual abuse in
      more than half of the cases. In twenty-five cases, the main request was a
      separation from the family. Eighteen adolescents were lost from our medical
      follow-up after reporting. Thirty-two reports to legal authorities had led to a
      hearing by a juvenile judge answered favorably in two-thirds of the cases, after
      a mean period of 26 days. All the subjects for whom a separation from the family
      was not requested in the report remained at home. CONCLUSION--A simple telephone
      call is enough to gather information about the following of reports and enables
      an evaluation of the relevancy of its requests. The interface between the health
      care and legal systems needs improving through better coordination. Pediatricians
      should be leaders in this field.

PMID- 7640735
TI  - [Precocious puberty and hypothalamic hamartoma: treatment with triptorelin during
      eight years].
AB  - BACKGROUND: Hypothalamic hamartoma, a rare cause of true sexual precocity, may
      develop slowly so that its diagnosis may be late. CASE REPORT: A 7 1/2-month-old
      girl was admitted because she suffered from development of physical pubertal
      changes. Laboratory tests were consistent with premature activation of the
      hypothalamic-pituitary axis. Initial neuroradiological investigation failed to
      find any cause. The patient was given medroxyprogesterone that resulted in
      regression of secondary sexual characteristics but growth rates and skeletal
      maturity remained accelerated. For that reason, the patient was given
      triptorexine, LH-RH analogue, 18 months later that resulted in a deceleration of
      puberty growth rate and skeletal maturity. MRI performed at the age of 9 years
      showed a small hypothalamic hamartoma and the LH-RH analogue was stopped at the
      age of 10 years. CONCLUSION: MRI is now the best technique for investigating the
      hypothalamo-hypophyseal area.

PMID- 7640736
TI  - [Hemophagocytic syndrome in children infected by HIV. Apropos of 3 cases].
AB  - BACKGROUND: The hemophagocytic syndrome has previously been reported in different
      infectious diseases (EBV, CMV, tuberculosis...) but rarely in adults with AIDS
      and never in children suffering from AIDS. CASE REPORTS: A hemophagocytic
      syndrome was recognized during the follow-up of 3 children with AIDS. The first,
      a 9-year-old girl developed an acute EBV coinfection and was treated with shots
      of corticosteroids and vepesid but died shortly afterwards. The second patient, a
      3-year-old girl was infected with Aspergillus fumigatus for which she was given
      amphotericin B with a rapid improvement. The third patient, an 8-year-old boy had
      multi-resistant Streptococcus pneumoniae otitis and pneumonitis; his condition
      improved rapidly with adapted antibiotherapy. DISCUSSION: The HIV-hemophagocytic
      syndrome is not exceptional in HIV infection because of the association of
      immunodeficiency and resulting superinfections. Its diagnosis and treatment
      should be etiologic. Severe cases without etiology could benefit from
      chemotherapy. CONCLUSION: Management and outcome of this potentially lethal
      syndrome might depend on the identification of a curable infectious cause.

PMID- 7640737
TI  - [Early manifestations of Tangier disease].
AB  - BACKGROUND: The diagnosis of Tangier disease in childhood is based on the
      specific aspect of tonsils or by screening relatives of affected subjects. CASE
      REPORT: A moderately enlarged liver associated with splenomegaly was found upon
      routine physical examination of a 3 month-old breast-fed boy, born in Turkey from
      consanguineous parents. Laboratory studies disclosed moderate increase in serum
      alanine aminotransferase activity (ALAT 52 UI/l, N < 30). The diagnosis of
      Tangier disease was confirmed by studies of plasma cholesterol and apolipoprotein
      A. By 8 months of age, the patient had enlarged orange tonsils. Small cervical,
      axillary and inguinal lymphadenopathies were present. The tonsilar and adenoidal
      tissues were removed at 18 months of age because the patient suffered from
      chronic airway obstruction. Colonoscopic examination revealed tiny flat orange
      spots, 1 to 2 mm in diameter, scattered throughout the rectosigmoidal and colonic
      mucosa. Survey of the family led to the discovery of one sister, with
      asymptomatic apolipoprotein Al deficiency and a normal sister, while the parents
      were heterozygotes for Tangier disease. CONCLUSION: Enlarged liver associated
      with a moderate level in serum aminotransferase may be an early manifestation of
      Tangier disease in infants. Rectosigmoidal and colonic lesions may be convenient
      for biopsy when tonsillectomy is not indicated.

PMID- 7640738
TI  - [Conjoined omphalopagous twins separated at fifteen days of age].
AB  - BACKGROUND: Conjoined (siamese) twins represent a rare situation which may occur
      in 1 of every 50,000 births. A prenatal diagnosis usually leads to stopping
      pregnancy. We report a case with successful surgical separation at the age of 15
      days. CASE REPORT: Ultrasonographic examination at 20 weeks of gestation showed
      omphalopagus siamese joined at the abdomen from the xiphoid process to the
      umbilicus. Conjoined structures included liver. There was a multicystic right
      kidney in one twin, without other malformation. Karyotype was normal, 46XX. The
      mother refused interruption of her pregnancy. Both girls were born by cesarean
      section. Angiography, magnetic resonance imaging and intravenous urography
      confirmed the ultrasound examination. There was no cross circulation into the
      liver and the gastrointestinal tract was not conjoined. The twins were separated
      at 15 days of age with right heminephrectomy of the multicystic kidney. The girls
      are now 16 months old and are in very good health. CONCLUSION: Prognosis of
      siamese twins depends on the nature of joined structures and presence of
      malformations. Ultrasonographic examination during pregnancy shows the
      possibility of surgical separation, which is performed by a double anesthetic and
      surgical pediatric team. Preoperative investigations must include MRI.

PMID- 7640739
TI  - [Familial form of pyknodysostosis with hematologic manifestations in a child].
AB  - BACKGROUND: Pyknodysostosis is characterized by post-natal onset of short-limbed
      short stature and generalized hyperostosis. It must be differentiated from
      osteopetrosis with precocious manifestations in which hyperostosis may crowd the
      marrow cavity with extramedullary hematopoiesis. CASE REPORTS: A boy, born from
      consanguineous parents presented with classical features of pyknodysostosis:
      short-limbed stature, large skull, frontal bossing, wide anterior fontanelle and
      tendency to fracture. His sister had the same features at the age of 3 months;
      she had hepatosplenomegaly at the age of 5 months with anemia, erythroblastosis
      (13%), myelemia and, at 10 months, thrombocytopenia. CONCLUSION: Hyperosostis can
      be complicated by development of such severe hematological manifestations as
      classically seen in osteopetrosis. Differential diagnosis between both entities
      is based upon radioclinical investigation.

PMID- 7640740
TI  - [Peak bone mass: facts and uncertainties].
AB  - Peak bone mass, which can be defined as the amount of bony tissue present at the
      end of the skeletal maturation, is an important determinant of osteoporotic
      fracture risk in adulthood. The techniques of single or dual energy
      absorptiometry measure the so-called "areal" or "surface" bone mineral density
      (BMD), a variable which has been shown to be directly related to bone strength.
      During puberty the gender difference in bone mass becomes expressed. This
      difference appears to be essentially due to a more prolonged bone maturation
      period in males than in females, with a larger increase in bone size and cortical
      thickness, as there is no significant sex difference in the volumetric trabecular
      density at the end of pubertal maturation. At the beginning of the 3rd decade,
      there is a large variability in the normal values of areal BMD in axial and
      appendicular skeleton. This large variance, which is observed at sites
      particularly susceptible to osteoporotic fractures in adulthood, such as lumbar
      spine and femoral neck, is barely reduced after correction for statural height,
      and does not appear to substantially increase during adult life. It is generally
      accepted that peak bone mass at any skeletal site is attained in both sexes
      during the mid-thirties. However, recent studies indicate that in healthy
      caucasian females, bone mass accumulation can virtually be completed before the
      end of the second decade, for both lumbar spine and femoral neck. Several
      variables are supposed to influence bone mass accumulation during growth:
      heredity, sex, diet components, endocrine factors, mechanical forces, and
      exposure to risk factors.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7640741
TI  - [Hyperexplexia].
AB  - Hyperexplexia is a disease of neonatal onset characterized by an exaggerated
      startle reflex. Early diagnosis is important to rule out epilepsy. Clinical
      findings are mainly hypertony and generalized startle reflex which is exaggerated
      by tiredness and some exogenous stimuli. Electroencephalogram is normal. The
      expression of the disease is variable including minor forms that may be unnoticed
      and major forms with arthrogryposis-like symptoms, orthopedic complications,
      false passages, apnea and even sudden infant death (SID). The evolution is
      generally benign and symptoms disappear within 2 or 3 years. A neuromotor
      retardation is often present, without intellectual deficit. In severe forms, the
      risk of SID requires a multidisciplinary follow-up including monitoring and
      treatment with clonazepam. A low GABA level in cerebrospinal fluid has been
      reported. Present etiological hypotheses include neuromediator and/or receptor
      dysfunction.

PMID- 7640742
TI  - [Psychologic management of extreme prematurity].
AB  - The ongoing progress in neonatal intensive care is modifying the psychic context
      of prematurity for all the partners, infants as well as parents and physicians.
      Comfort and prognosis of preterm infants have much improved. Since newborns under
      24 weeks of gestational age are now surviving, they spend approximately half the
      duration of pregnancy out of the maternal uterus. All the psychological issues of
      such an early separation have to be considered, including the developmental
      outcome of a sensorial environment which is quite different from the intra
      uterine one. Research has been developing in this field. The cooperation between
      neonatalogists and psychologists has been profitable to parents. Problems linked
      to the separation, such as difficulty in representing the infant, are no more
      frequent owing to the attention paid to the mother-child bond and subsequent
      early contacts. What is forward now is the impact of an hyper technical world of
      intensive care on the parents, and of the strange aspect of the tiny baby
      surrounded by engines and tubes. Such an overpresence of reality often results in
      a reaction of traumatic daziness among parents. The cooperation of the whole
      staff is necessary for the resumption of an imaginary process of psychic
      functioning. Finally, the survival of very-low-birth-weight infants confronts the
      neonatalogists with some delicate ethical questions. Psychiatrists and
      psychologists might have an important part to play in aiding the profession in
      its sorting out of these ethical issues.

PMID- 7640743
TI  - [Nutritional aspects in Duchenne muscular dystrophy].

PMID- 7640744
TI  - [Urodynamic exploration in functional micturition disorders in children].
AB  - Urodynamic investigation in paediatric patients is presented. The practical
      aspects and usefulness of each method are discussed in the cases of functional
      micturition disorders based upon the most significant results from the literature
      and the author's experience. Urodynamic investigation in children provides a
      pathophysiological explanation of bladder-sphincter dysfunction and guidelines
      for appropriate treatment.

PMID- 7640745
TI  - [Use of nalbuphine during labor].

PMID- 7640746
TI  - [Subcortical laminar heterotopia and lissencephaly: brain malformations with X
      linked dominant heredity?].

PMID- 7640747
TI  - [Lyell syndrome following administration of erythromycin-sulfafurazole and
      morniflumate].

PMID- 7640748
TI  - [Identification of the gene determining spinal muscular atrophy: perspectives].

PMID- 7640749
TI  - [Diseases of the endoplasmic reticulum and the Golgi apparatus: glycosylation
      deficiencies of glycoproteins].

PMID- 7640750
TI  - [Encephalopathy induced by arterial hypertension: clinical, radiological and
      therapeutical aspects].
AB  - BACKGROUND: Neuroradiological features of hypertensive encephalopathy are not yet
      well-known. PATIENTS AND METHODS: The clinical manifestations, neuroradiological
      aspects and treatment of four patients suffering from hypertensive encephalopathy
      were studied; special attention was paid to manifestations presented by one
      patient which appeared representative of the usual manifestations of hypertensive
      encephalopathy. RESULTS: The main clinical features were visual disturbances (n =
      4); altered consciousness (n = 2) and seizures (n = 3). Visual disturbances
      resulted from cortical lesions (n = 4) associated with optic nerve damage and
      retinopathy (n = 2). Cerebral imaging showed low density images (CT scan) and
      hypersignal (MRI, T2 sequence) located in parieto-occipital cortical ribbon and
      adjacent white matter from the first 24 hours following the onset of neurologic
      symptoms. In the studied patient, the abnormal images resolved within 1 month
      after the onset of the disease. Unilateral infarction of the anterior visual
      pathway affected two patients in whom: 1) hypertension remaining undetected for a
      long time was revealed by neurological signs; 2) visual impairment was preceded
      by an hypotensive episode induced by antihypertensive therapy. CONCLUSIONS:
      Neuroradiological features of hypertensive encephalopathy are useful in
      establishing the diagnosis. A gradual reduction of blood pressure could prevent
      the risk of visual complications.

PMID- 7640751
TI  - [The individualization of care practices for twins during the first year].
AB  - BACKGROUND: Mothers of twins have some difficulties to individualize their child
      raising activities during the first year. This study was aimed to determine
      factors influencing such activities. POPULATION AND METHODS: Thirty-seven pairs
      of twins born after 36 weeks of gestation and weighing more than 2,000 g were
      included in the study. Relationships between the parents and their children were
      studied from questionnaires concerning activities during the first trimester and
      the end of the first year of age. Each item concerning organization of meals and
      sleeping was graded 1 to 3 according to the degree of individualization of the
      care. Items concerning support of the mother by the father or other people were
      graded 1 to 3 according to the degree of this assistance. The physical and
      psychological status of the mother was also graded according to the presence or
      not of asthenia and/or depression. Home activities of the mother were also
      observed. RESULTS: The state of the mother during the first few months had an
      impact on her mothering behavior: tired or depressed mothers tend to treat the
      twins collectively and simultaneously. No link was found between social, paternal
      or general familial support and the degree of individualization in the maternal
      behaviors. CONCLUSIONS: Several factors can interfere with the psychological
      repercussions of a twin birth on the mother and subsequent psychoemotional
      development of children. Further studies are necessary to understand how each
      parent contributes to the organization of the family system.

PMID- 7640752
TI  - [Milk feeding of infants and cow's milk protein hypersensitivity].
AB  - BACKGROUND: Cow milk protein intolerance (CMPI) is characterized by a wide range
      of symptoms and signs affecting the gastro-intestinal tract, the respiratory
      system and the skin. A better definition, a stricter application of diagnostic
      criteria and critical evaluation of certain immunologic correlates can contribute
      to a better understanding and preventive treatment of this entity. POPULATION AND
      METHODS: Two hundred-seventeen infants with CMPI seen between January 1980 and
      December 1993 were included in the study. They were classified into two groups:
      1) acute reaginic CMPI (type I): 125 infants and 2) CMP enteropathy or colitis
      (type III or IV): 92 infants, according to classical diagnostic criteria. Careful
      investigation concerning the type of milk feeding (breast or artificial) proposed
      prior to clinical manifestations was performed. RESULTS: Among the 125 infants
      (aged 3 to 20 weeks) with acute reaginic CMPI, 121 (97%) had been breast-fed with
      a sudden weaning; 30 of these infants had also received one to three formula
      bottles during the first 3 days of life and 14 certainly had not received such
      formula bottles. Among the 92 infants with CMPI, type III or IV, 33 (38%) had
      been exclusively breast-fed, a figure quite similar to the breast feeding
      incidence in our region. CONCLUSIONS: These results clearly show the importance
      of breast-feeding in the personal history of CMPI. Acute reaginic type of CMPI is
      favored by early ingestion of formula bottles in breast-fed infants and by early
      sudden weaning. Hypoallergenic formula in five cases was unable to protect
      infants against further allergic manifestation.

PMID- 7640753
TI  - [Epidemiological study of sequelae of injuries in adolescents].
AB  - BACKGROUND: In all industrialized countries, injuries constitute the primary
      public health problem during adolescence; study of long-term outcome of injuries
      to adolescents remains poor. POPULATION AND METHODS: A longitudinal
      epidemiological study performed on 8,140 students in 17 secondary schools in
      Paris and the Department of the Cote-d'Or followed the development over one year
      of 777 adolescents who had injuries in 1990. All injuries, both within and
      outside school, were included if they fulfilled the following criteria: school
      absence or excused from vocational training exceeding or equal to 2 days, or
      excused from physical education classes for at least 14 days. RESULTS: One year
      after the injury, 13% of the adolescents were still bothered by their injury,
      especially those who were older and the girls. Among described impairments,
      musculo-skeletal problems (88% of cases) were the major difficulty. These
      impairments were primarily in the lower limbs (53%). Unaesthetic scars were found
      in 17% of cases, and a psychological impact was found in 16.5% of the
      adolescents. The presence of sequelae was related to the type of initial lesion
      (present in 24% of head injuries and in 16% of cases affecting the lower limbs).
      The most serious difficulties were caused by dislocations, serious sprains and
      fractures. One year after the injury, sequelae were serious in 10% of those
      adolescents still experiencing problems; they had some impact on the daily life
      of the adolescents in 36% of cases, that is, 5% of all adolescents experiencing
      an injury. These sequelae were responsible for a high level of consumption of
      medical services. CONCLUSIONS: Although observed sequelae were relatively minor,
      the high frequency of injuries during adolescence, as well as their high economic
      costs, justify the most appropriate care available for victims of injuries, even
      those which appear benign. In addition, longitudinal studies should be prepared
      using adapted tools (scales for the evaluation of the gravity of injury
      sequelae).

PMID- 7640754
TI  - [Hydrops fetalis and G-6-PD deficiency].
AB  - BACKGROUND: Antenatal manifestation of glucose-6-phosphate dehydrogenase
      deficiency is uncommon. CASE REPORT: A male was born by caesarian section at 34
      weeks of GA for hydrops fetalis (HF). Fetal ultrasonography showed hydrops
      fetalis for the first time at 24 weeks of GA. All investigations were normal,
      except moderate anemia (Hb: 11.5 g/dl) and important erythroblastosis (67%) in
      the fetal blood sampling at 25 weeks. HF spontaneously resolved, until caesarian
      section at 34 weeks for recurrence of HF. Hydrops and neonatal anemia were
      successfully treated with pleural and peritoneal aspiration and blood
      transfusion. At the age of 4 months, investigations showed low levels of G-6-PD
      activity. At the age of 12 months, the child's growth and development appeared to
      be appropriate. CONCLUSIONS: Diagnosis of G-6-PD deficiency must be suspected
      when HF due to anemia occurs in a population at risk; it could be confirmed by an
      enzyme study of fetal red blood cells.

PMID- 7640755
TI  - [Melanotic neuroectodermal tumor in an infant].
AB  - BACKGROUND: Melanotic neuroectodermal tumor is a mostly benign tumor, rare in
      childhood, essentially located in the head and neck region. CASE REPORT: A two
      month-old girl was seen for a rapidly increasing odontogenic tumor which appeared
      cystic at the CT scan. After enucleation, this premaxillar tumor recurred one
      month later with an osteogenic aspect at the CT scan. Urine catecholamine
      excretion was normal; Methyl Iodo Benzyl Guanidin scintigraphy failed to show any
      fixation and electron microscopy examination of the biopsy showed several
      varieties of melanocytes. A partial maxillectomy was performed by oral approach.
      The patient is well 4 1/2 years later. CONCLUSION: This observation confirms the
      recurrence potential of this tumor and the cosmetic interest of the oral surgical
      approach.

PMID- 7640756
TI  - [A rare complication of multiple exostoses: hemothorax].
AB  - BACKGROUND: Hemothorax is a rare complication of hereditary multiple exostosis.
      CASE REPORT: A 12 year-old boy suffered from abrupt thoracic pain, firstly
      attributed to pleural effusion. He had hereditary multiple exostosis known since
      the age of 9 years. The patients was given anti-inflammatory drugs and
      erythromycin but the pleural effusion became more abundant 6 days later requiring
      thoracentesis which showed hemothorax. All bacteriological and cytologic
      investigations were negative. X rays, ultra-sonography and CT scan showed several
      costal exostoses developing into the thoracic cavity. The hemothorax disappeared
      within 12 days and the patient was well 4 months later, without pleural sequelae.
      CONCLUSIONS: Hemothorax may be due to internal costal exostosis. It may be cured
      with thoracentesis; more aggressive therapy should be performed in exceptional
      cases with severe and/or recurrent bleeding.

PMID- 7640757
TI  - [Clinical heterogeneity of Townes-Brocks syndrome].
AB  - BACKGROUND: Townes-Brocks syndrome (TBS) is a rare autosomal dominant entity
      mainly characterized by ano-rectal, ear and extremities abnormalities with
      variable clinical expression. CASE REPORTS: The first case had ear and
      extremities, but not anorectal, abnormalities; a Pierre-Robin sequence with
      esophageal atresia was also observed. The second case had the classical triad of
      abnormalities also associated with tetralogy of Fallot which has been only once
      reported in the literature. CONCLUSIONS: Both cases are other examples of the
      frequent clinical variability observed in this syndrome explaining diagnostic
      difficulties in the absence of a specific marker.

PMID- 7640758
TI  - [Vascular tracheal compression presenting as bronchiolitis in infants].
AB  - BACKGROUND: Anomalies of the aortic arch and pulmonary arteries may produce
      compression of the trachea with chronic stridor or wheezing aggravated by crying,
      feeding and flexion of the neck. CASE REPORTS: Three infants, 3, 5 and 2 months
      old, respectively, were admitted suffering from acute bronchiolitis. The first
      patient had intermittent wheezing for one month; lateral chest X-rays showed an
      opaque area inserted between the trachea and oesophagus and computed tomography
      showed pulmonary artery sling with tracheal stenosis which was successfully
      operated. The second patient displayed pulmonary atelectasia which required
      bronchoscopy; this technique showed tracheal stenosis which was due to pulmonary
      artery sling. The third patient had a history of congenital stridor: he required
      endotracheal intubation; a bronchoscopy performed because persistent pulmonary
      atelectasia showed tracheal stenosis which was secondary to a double aortic arch.
      The condition was improved after surgical correction. CONCLUSIONS: A history of
      stridor and/or wheezing in patients admitted for bronchiolitis must lead to
      consider the possibility of vascular compression of the trachea and to perform
      specific investigations.

PMID- 7640759
TI  - [Hereditary nephrogenic diabetes insipidus].
AB  - Congenital nephrogenic diabetes insipidus (NDI) is a rare inherited disorder
      characterized by the inability of the kidney to concentrate urine in response to
      vasopressin (AVP). Following the recent characterization of the cDNA and genomics
      sequences encoding the human V2 receptor to AVP (AVPR2), X-linked NDI has been
      found to be due to mutations in the AVPR2 gene that maps to the chromosome Xq28
      region. To date more than 30 mutations, insertions or deletions have been
      reported in independent families, without any significant differences in the
      phenotypic expression of the disease. The AVPR2 is a member of the superfamily of
      7 transmembrane domain, G protein-coupled receptor, linked to cyclic AMP second
      messenger system. Other types of inheritance have been described in NDI, and
      recently, a mutation of the aquaporin-2 gene, encoding a water channel of the
      renal collecting duct, has been reported in an autosomal recessive form of NDI.

PMID- 7640760
TI  - [Benefits and risks of fluoride supplements].
AB  - Fluoride is an essential trace element. It is incorporated in calcified tissues.
      At doses lower than 1.5 mg/day, fluoride has a prophylactic action against dental
      caries by absorption on the enamel surface. At doses ranging from 15 to 25
      mg/day, it is used as a therapeutic agent in adults, in the treatment of post
      menopausal osteoporosis with vertebral crush fractures. At high doses, fluoride
      may induce skeletal fluorosis leading in children to pseudorachitism. In
      children, fluoride supplement has been recommended for several years, as a
      prophylactic agent against dental caries. It may be given either as dentifrices
      and toothwash solutions, easy to use and economic but contraindicated in very
      young children; or as tablets, sure and effective but requiring a daily intake;
      or as domestic salts supplemented with 250 mg/kg. Fluoride supplement may also be
      given through drinking water. Fluoride content is limited to 1.5 mg/l but some
      mineral waters contain high amounts of fluoride and may have a beneficial effect
      on bone mass. In order to prevent an excessive fluoride intake in children and in
      adults, different forms of fluoride supplements must not be associated.

PMID- 7640761
TI  - [Helicobacter pylori infection in children].
AB  - Helicobacter pylori (Hp) is a pathogen of human gastric mucosa and is considered
      as the major cause of chronic gastritis and duodenal ulcer disease recurrence.
      The prevalence rate of Hp infection increases with age and is related to low
      socioeconomic status in childhood. Childhood appears to be a high-risk period for
      Hp infection. Clinical and histological features of Hp infection are variable and
      often moderate in children. This is probably due to both genetic and
      environmental factors. Abdominal pain is the most frequent symptom and is usually
      associated with a mild chronic gastritis. Serology, 13C-urea breath test,
      bacterial culture and histological examination of biopsy specimen can be used for
      the diagnosis of Hp infection. Eradication of Hp infection is difficult and
      indications and modalities of treatment need to be specified in children. A
      better knowledge of epidemiology and natural history of Hp infection in childhood
      should permit to answer these questions.

PMID- 7640762
TI  - [Research on bone marrow involvement in the diagnosis of solid tumors in
      children. Methods, results and interpretation].
AB  - The assessment of bone marrow involvement by tumor cells remains an essential
      problem at diagnosis in pediatric solid tumors. Besides the conventional
      cytological and histological methods, some modern cell density separation
      techniques have been described in order to improve the detection of minimal or
      scattered bone marrow involvement. Immunological or genetical (molecular biology)
      tools can be used for the recognition of separated cells. In terms of
      investigations, MRI and MIBG radionucleide scan, although giving no definite
      proof, have the ability to macroscopically study the scattering of bone marrow
      invasion in the particular case of neuroblastoma. In some pediatric tumors,
      especially neuroblastomas and non Hodgkin lymphomas, an extensive bone marrow
      investigation is mandatory at diagnosis. Such an investigation is only necessary
      in case of particular criteria at diagnosis of Hodgkin's disease, Ewing'
      sarcomas, rhabdomyosarcomas and retinoblastomas. All other pediatric solid tumors
      do not need to be investigated in terms of bone marrow involvement at diagnosis,
      with the exceptions of advanced disseminated disease or if an autologous bone
      marrow transplantation is planned.

PMID- 7640763
TI  - [Radiologic case of the month. Familial hypercalcemia with hypocalciuria].

PMID- 7640764
TI  - [What is the future of pediatrics in the coming years?].

PMID- 7640765
TI  - [Mortality and short-term outcome of low birth-weight infants 1500 g or less in
      Reunion].

PMID- 7640766
TI  - [Repartition of frequency of main mutation (delta F508) in mucoviscidosis in
      France: results of multicenter study of 1030 unrelated families].

PMID- 7640767
TI  - [Pediatric emergencies in Le Havre hospitals: analysis of admission modalities].

PMID- 7640768
TI  - Optimization of a modified electrode for the sensitive and selective detection of
      alpha-dipeptides.
AB  - Sensitive and selective detection of dipeptides is important in neurochemistry.
      We have developed a flexible detection scheme for dipeptides based on a modified
      carbon electrode. The modification arises from the anodic treatment of the carbon
      electrode in alkaline solution. The flexibility of the detection scheme arises
      from the different conditions used in both the modification and the detection. It
      is shown that the modification step requires the presence of cupric ion, while
      the detection step does not. On the other hand, it is shown that the presence of
      copper in the detection eluent, as well as the pH of the environment, can be used
      in controlling the selectivity of the modified electrode. For example, the
      modified electrode is more selective for alpha-dipeptides over beta- and gamma
      dipeptides as well as amino acids at pH 9.8, whereas it is selective for all
      dipeptides over amino acids at pH 8.0. Detection limits of dipeptides on the
      order of 10 nM were achieved at pH 8.0 by flow-injection analysis with a knotted
      Teflon tubing connecting the injector and the detector that gave a typical peak
      volume of about 0.50 ml at 1.0 ml/min. From surface analysis it is shown that the
      oxygenation of the glassy carbon electrode gives rise to the selectivity. The
      oxidation of dipeptides at the modified electrode is completely inhibited by 10
      mM Mg2+ in the eluent.

PMID- 7640769
TI  - Chromatographic behaviour of opioid peptides containing beta-methylphenylalanine
      isomers.
AB  - A reversed-phase high-performance liquid chromatographic (RP-HPLC) method was
      developed to obtain pure erythro[2S3S, 2R3R]- and threo[2S3R, 2R3S]-beta
      methylphenylalanine. These amino acids were incorporated into an enkephalin, H
      Tyr-D-Ala-Gly-beta-MePhe-Val-Val-Gly-NH2, and into a deltorphin C, H-Tyr-D-Ala
      beta-MePhe-Asp-Val-Val-Gly-NH2, analogue, which yielded four diastereoisomers of
      the peptides. The diastereoisomers were separated on different columns and with
      different eluent systems. The sequence of elution of the peptide diastereoisomers
      was determined after hydrolysis of the peptides. For identification of the beta
      methylphenylalanine enantiomers, enzymatic degradation and an RP-HPLC method were
      used, with application of 1-fluoro-2,4-dinitrophenyl-5-L-alanine amide as
      derivatizing reagent.

PMID- 7640770
TI  - Enantiomeric separation of basic drugs using N-benzyloxycarbonylglyclyl-L-proline
      as counter ion in methanol.
AB  - Direct separation of enantiomeric amines using mainly N-benzyloxycarbonylglycyl-L
      proline (L-ZGP) but also N-benzyloxycarbonylglyclglcyl-L-proline (L-ZGGP) as the
      chiral counter ion in methanol is described. The solid phase was Hypercarb porous
      graphitic carbon. Several amines of pharmacological interest (e.g., alprenolol,
      sotalol, terbutaline, promethazine and trimipramine) were separated with high
      enantioselectivity (alpha = 1.16-1.98) using L-ZGP and L-ZGGP as chiral
      selectors. In accordance with ion-pair chromatography, the retention of the
      enantiomeric amines was found to increase with increasing concentration of the
      anionic form of L-ZGP. Addition of a base (sodium hydroxide or an alkylamine) in
      excess of L-ZGP gave rise to a decrease in retention and enantioselectivity. The
      enantioselective retention was also affected by adding 2-propanol or acetonitrile
      to the mobile phase.

PMID- 7640771
TI  - Purification of preparative quantities of group B Streptococcus type III
      oligosaccharides.
AB  - Many bacterial capsular polysaccharides are regularly repeating units of
      oligosaccharides. Bacterial oligosaccharides have been used in neoglycoconjugate
      vaccines and as reagents in the study of specific antibody binding.
      Unfortunately, separation methods have not been adequate for the purification of
      preparative quantities of bacterial oligosaccharides. Here we describe a size
      exclusion procedure that resulted in the resolution of group B Streptococcus type
      III oligosaccharides composed of 4-25 sugars.

PMID- 7640772
TI  - Separation of hydroxyl protected heparin derived disaccharides using reversed
      phase high-performance liquid chromatography.
AB  - A simple and efficient method for the separation of hydrophobic derivatives of
      glycosaminoglycan-derived disaccharides is described. Hydroxyl-protected
      derivatives of a trisulfated disaccharide, prepared from heparin using heparin
      lyase, were separated by reversed-phase high-performance liquid chromatography.
      These disaccharide derivatives differed by the number, position, and
      stereochemistry of acetyl and pivaloyl groups. Separation was achieved on a C18
      column using a reversed gradient of ammonium sulfate in water. This method has
      application in the purification of disaccharide derivatives being used as chiral
      synthons in the preparation of higher oligosaccharides.

PMID- 7640773
TI  - Determination of anions in human and animal tear fluid and blood serum by ion
      chromatography.
AB  - An important factor contributing to the development of ion chromatography (IC)
      has been the need for repetitive analyses of samples with high ionic contents and
      samples available in microvolumes. IC was selected for the determination of Cl,
      NO3, SO(2-)4 and PO(3-)4 anions in tear fluid and serum from ten human volunteers
      of both sexes, seven young-adult black vultures (Coragyps atratus) and three
      young-adult chickens (Gallus gallus domesticus). The samples were analysed on a
      Dionex Model 2000i/SP ion-exchange chromatograph equipped with an anion guard
      column (Dionex IonPac AG4A), anion separator column (Dionex IonPac AS4A),
      suppressor column (Dionex AMMS-II) and a conductivity detector. The flow-rte of
      the mobile phase, 1.7 mM NaHCO3 - 1.8 mM Na2CO3 was set at 2.0 ml/min. The R.S.D.
      was calculated to be less than 1.5% for all anions. In the human, black vulture
      and chicken serum samples, the NO3, PO(3-)4 and SO(2-)4 anion contents were
      higher than in tears; for Cl the reverse was found. No correlation was found
      amongst the anion concentrations present in the tear fluid and blood serum in all
      samples (p > 0.05). With no sample treatment, column maintenance was required.

PMID- 7640774
TI  - Direct determination of seleno-amino acids in biological tissues by anion
      exchange separation and electrochemical detection.
AB  - Several studies have described the determination of selenium in protein extracts
      from tissues of marine or terrestrial animals, but have not identified the
      different chemical forms of selenium that are present. Selenium may be present as
      seleno-amino acids. Selenocysteine, for example, is a normal component of
      glutathione peroxidase, an antioxidant enzyme which may behave like other
      antioxidants, such as vitamin E, protecting tissues against methylmercury
      toxicity. The present study illustrates a method for the characterization of
      seleno-amino acids, such as selenocysteine and selenomethionine, in proteins
      extracted from the liver of marine mammals. The mechanism of detoxification of
      methylmercury, which involves seleno-compounds, is identified. The analytical
      determination was carried out using high-performance anion-exchange
      chromatography coupled with integrated pulsed amperometric detection (HPAEC
      IPAD). This method allows the direct determination of underivatized amino acids,
      eliminating the procedure of pre- or postcolumn derivatization. The
      chromatographic separation was carried out on an anion-exchange column using a
      quaternary gradient elution. In order to optimize this method, interferences of
      amino acids and the influence of pH and ionic strength on the separation and
      electrochemical detection were studied. The IPAD response for the direct
      detection of amino acids is optimum at pH > 11. The detection limit (S/N = 3) for
      selenocysteine was found to be 450 micrograms/l. The application of this method
      for the identification of seleno-amino acids in protein hydrolysates is also
      shown.

PMID- 7640775
TI  - Nitric oxide in biological fluids: analysis of nitrite and nitrate by high
      performance ion chromatography.
AB  - The analysis of nitric oxide-derived nitrite and nitrate ions in biological
      fluids represents a proven strategy for determining nitric oxide participation in
      a diverse range of physiological and pathophysiological processes in vivo. In
      this article we describe a versatile method for the simultaneous measurement of
      NO2- and NO3- anions in both plasma and isolated tumour models based on anion
      exchange chromatography with spectrophotometric detection (214 nm). This method
      compares well with the capillary electrophoresis technique, exhibiting an
      equivalent sensitivity for NO2-/NO3- anions and short run-times, i.e. not greater
      than 4 min. Comparisons are also made with two alternative but less satisfactory
      methods which employ ion-exchange or reversed-phase ion-pair chromatography with
      conductimetric as well as spectrophotometric detection. Technical problems
      associated with each method, particularly those arising from nitrate
      contamination, have been addressed.

PMID- 7640776
TI  - Ion chromatography as potential reference methodology for the determination of
      total sodium and potassium in human serum.
AB  - The potential of ion chromatography to serve as a new reference method principle
      for the determination of total sodium and potassium in human serum was
      investigated. Sample pretreatment consisted of acidic dilution and filtration and
      detection was based on conductivity. Methods for the separate and simultaneous
      determination of both analytes were investigated. Further, the influence of
      calibration (using either a single-point calibration or a standard curve) on
      method imprecision, inaccuracy and analysis time was examined. The best method
      performance was achieved by separate analysis using single-point calibration with
      bracketing analysis scheme. For this variant, the mean total coefficient of
      variation for sodium and potassium was 1.0% and the mean method bias was -0.2%
      for sodium and  2% for potassium, as determined with three control materials from
      the National Institute of Standards and Technology. Our results are comparable to
      those of reference methods based on flame atomic emission spectrometry.
      Therefore, we consider ion chromatography as a valuable reference methodology for
      the determination of total sodium potassium in human serum.

PMID- 7640777
TI  - Plasma level determination of 1,4-butanedisulphonate by ion chromatography and
      conductimetric detection.
AB  - A rapid, specific and reproducible liquid chromatographic method was developed
      for the determination of 1,4-butanedisulphonate in plasma. The method involves
      protein precipitation with perchloric acid, precipitation of perchlorate ions by
      addition of potassium carbonate followed by ion chromatography on an ion-exchange
      column connected with a conductimetric detector. Calibration graphs were linear
      over the concentration range 2.5-25 micrograms/ml; the intra-assay precision was
      < or equal to 3.6% and the inter-assay precision was < or equal to 5.8%. The
      analyte was stable in plasma and in perchloric acid at 37 degrees C for 24 h. The
      assay procedure was applied to monitoring plasma levels in animals receiving
      chronic intravenous and oral administration of the analyte.

PMID- 7640778
TI  - Analysis of the acidic microenvironment in murine tumours by high-performance ion
      chromatography.
AB  - High-performance ion chromatography (HPIC) has been utilised to probe the
      biochemistry associated with changes in tumour pH following total vascular
      occlusion. Samples from the tumour extracellular compartment were obtained by
      insertion of a microdialysis probe and analysed by HPIC with conductivity
      detection. Separations were carried out by ion-exclusion chromatography using an
      IonPac ICE AS1 weak-acid column. The eluent (0.5 mM octanesulphonic acid) was
      chemically suppressed with 5 mM tetrabutylammonium hydroxide through a
      micromembrane suppressor. After complete vascular occlusion induced by a clamp,
      lactate levels increased in the extracellular compartment.

PMID- 7640779
TI  - CAG triplet analysis in families with androgen insensitivity syndrome by
      capillary electrophoresis in polymer networks.
AB  - The potential use of capillary zone electrophoresis in polymer networks (linear
      polymers above the entanglement threshold, added to the background electrolyte
      for sieving purposes) for analysis of DNA fragments amplified by a polymerase
      chain reaction, is shown. In typical runs, the capillary is filled with Tris
      borate-EDTA buffer, at pH 8.3, containing 6% linear polyacrylamide as a dynamic
      sieving matrix. Such formulations allow replenishing the capillary with fresh
      sieving solution when resolution decays after prolonged use (typically > 30
      injections per capillary are obtained). The DNA fragments are detected by their
      intrinsic absorbance at 254 nm. This system has been applied to the analysis of
      CAG triplet polymorphism in families carrying the androgen insensitivity
      syndrome. While easy separation is obtained for fragments 139 base pairs (bp) and
      160 bp (in families carrying a difference of 7 CAG repeats) even more difficult
      cases (such as those of families exhibiting fragments of 136 and 139 bp, thus
      differing by only one CAG repeat) are resolved with precision and diagnostic
      value.

PMID- 7640780
TI  - Mt. Washington Pediatric Hospital, Baltimore, MD.

PMID- 7640781
TI  - What nursing has known all along.

PMID- 7640782
TI  - Stamping out chickenpox.

PMID- 7640783
TI  - RN produces health-related television program. Interview by Mary Jane Zusey .

PMID- 7640784
TI  - Home care for children with chronic illness.

PMID- 7640786
TI  - Management a la Disney.

PMID- 7640785
TI  - Colors of the spectrum. The pediatric nurse in managed ambulatory care.

PMID- 7640787
TI  - Management perspectives. I am a nursing executive in an institution whose goal is
      to change its culture to become more customer oriented.

PMID- 7640788
TI  - Pediatric nurse practitioners in specialty clinics.

PMID- 7640789
TI  - Summer vacation? Asthma camp nursing.

PMID- 7640790
TI  - Day care and nursing care come together.

PMID- 7640791
TI  - [Continuing education within the workplace. An instrument for the development of
      personnel].

PMID- 7640792
TI  - [The patient's will--a sample without value?].

PMID- 7640793
TI  - [Computer programs in the hospital. The automatic "dunce" has many good
      features].

PMID- 7640794
TI  - [No clear-cutting for the production of cellulose].

PMID- 7640795
TI  - [Nursing education in eastern Germany. Changes in Saxony are almost completed].

PMID- 7640796
TI  - [Dishes--colorful dots in the everyday life of the hospital].

PMID- 7640797
TI  - [Working time legislation 1994. Commentary regarding the domain of the hospital].

PMID- 7640798
TI  - [Interactions between nursing and therapeutic teams. Divide et impera--divide and
      conquer].

PMID- 7640800
TI  - [The first year of nursing education. Guidelines for the adjustment of nursing
      students].

PMID- 7640799
TI  - [Introduction into Chinese medicine. Use of acupuncture and homeopathy in the
      treatment of migraine].

PMID- 7640801
TI  - [Bremen nursing study courses. Qualification and professionalization].

PMID- 7640802
TI  - [The invisible ailment. Patients with epilepsy in the hospital].

PMID- 7640803
TI  - [Supervision of nursing teams in internal medicine. Interest in all professional
      groups].

PMID- 7640804
TI  - Hepatitis B virus and employment in the NHS.

PMID- 7640805
TI  - Antiplatelet antibodies.

PMID- 7640806
TI  - Rationalisation of colonoscopy surveillance services: the need for clearer
      guidelines.
AB  - Colonoscopic surveillance in premalignant conditions and after resection of
      colorectal cancer is necessary. However, it is expensive, time-consuming and
      patients find it unpleasant. Furthermore, limited resources exist. Cost
      effectiveness will depend upon a rational approach. This article is stimulated by
      the need for clearer guidelines.

PMID- 7640807
TI  - Psychiatric complications of corticosteroid therapy.
AB  - Despite limited evidence, the general consensus is that corticosteroids can cause
      psychiatric complications, mainly depression. This is most noticeable in high
      doses or in medical conditions with neuropsychiatric sequelae. The prognosis is
      usually good if corticosteroids are discontinued, but further study of the
      prevalence of psychiatric reactions, their mechanism of action and appropriate
      treatment is necessary.

PMID- 7640809
TI  - Examination of the breasts for surgical short cases.
AB  - For patients, examination of the breasts is a sensitive and sometimes anxious
      situation. Candidates should therefore display a thorough and confident technique
      aimed at reassuring both the patient and the examiner.

PMID- 7640808
TI  - Drug treatment in post-traumatic stress disorder.
AB  - As our knowledge of post-traumatic stress disorder grows, so new treatment
      strategies develop. This article evaluates the benefits and limitations of drug
      treatment, with reference to underlying neurobiological changes seen in the
      condition. Drug treatment has a beneficial role if used as part of a flexible,
      client-centred approach.

PMID- 7640810
TI  - Reducing the incidence of postoperative nausea and vomiting.
AB  - In the first part of this article (Vol 53(7) 1995, p.327), the physiology of
      vomiting and the factors known to influence postoperative nausea and vomiting
      (PONV) were summarised. In this second part the therapeutic options available to
      reduce the incidence of PONV are reviewed.

PMID- 7640811
TI  - How to do it in paediatrics. 4. Auxology.

PMID- 7640812
TI  - Assessment and management of snoring: a surgical perspective.
AB  - This article reviews the assessment and treatment options for both 'simple
      snorers' and those with obstructive sleep apnoea. Accurate assessment of all
      snorers is essential for optimal outcome and new surgical techniques now provide
      good symptom relief while maintaining normal palatal anatomy. The need for
      involvement of both respiratory physicians and otolaryngologists in the patient's
      care is emphasised.

PMID- 7640813
TI  - Optimal management of the heart-lung donor.
AB  - Optimising the management of the heart-lung donor may increase the number of
      organs suitable for transplantation. This can be achieved by understanding the
      pathophysiology of brain death and implementing therapeutic measures to
      counteract the deleterious effect of brain death on end-organ function.

PMID- 7640814
TI  - Ambulatory myocardial ischaemia in stable angina.
AB  - Episodes of ischaemic ST segment depression detected by continuous ambulatory
      electrocardiographic (Holter) monitoring have been extensively investigated for
      over two decades, but no consensus has emerged about their clinical significance.
      This review examines the prevalence and reported prognostic importance of
      ambulatory myocardial ischaemia in patients with stable angina, and discusses
      whether or not detection and treatment of ischaemic episodes in ambulant angina
      patients can be justified on the basis of the available evidence.

PMID- 7640815
TI  - Third-degree heart block during anaesthesia on two successive occasions.

PMID- 7640816
TI  - Consumer audit in the NHS.
AB  - Recent Department of Health publications and initiatives have emphasised the need
      to make services more responsive to the needs of patients. This article describes
      the consumer audit process, developed by the College of Health, involving a range
      of sensitive yet rigorous qualitative research processes to provide feedback from
      patients and their carers, in a form which is of practical and educational use to
      clinicians and managers and results in change and development.

PMID- 7640817
TI  - A preoperative gynaecological clinic.

PMID- 7640818
TI  - Gold to silver: reverse alchemy?

PMID- 7640819
TI  - Fear of being asleep.

PMID- 7640820
TI  - Preventable deaths after injury: why are the traditional 'vital' signs poor
      indicators of blood loss?

PMID- 7640821
TI  - Women attending an accident and emergency department after assaults.
AB  - Assaults on women are a distressing aspect of A&E work. In a combined prospective
      and retrospective study, covering a 6-month period, 282 female victims were
      identified (0.75% of attendances). Although most of the injuries were relatively
      minor the recording of historical and social factors was poor. Attempted follow
      up for counselling and support proved ineffective. Better education of the
      doctors regarding the documentation for such patients, assessment of the social
      dimensions of their needs and requirement for improving both their immediate care
      and long term follow-up are discussed.

PMID- 7640822
TI  - The effect of pre-hospital administration of intravenous nalbuphine on on-scene
      times.
AB  - The use of intravenous nalbuphine in pre-hospital settings by paramedics has been
      demonstrated to be safe and effective. We assessed the effect of this additional
      intervention by comparing the time spent on-scene by ambulance crews treating
      patients with fractures of the tibia and fibula who received intravenous
      nalbuphine with those who had placement of an intravenous cannula alone and those
      who had neither cannula nor nalbuphine. The mean on-scene times were 17.1 min
      without cannulation, 29.9 min for cannulation without nalbuphine and 37.5 min for
      cannulation and administration of nalbuphine. The benefits of effective pre
      hospital analgesia thus have a cost in terms of time. Continued audit of
      interventions and on-scene times is important to prevent inappropriate delays in
      pre-hospital care which may cause clinical and operational problems.

PMID- 7640823
TI  - Who should see eye casualties?: a comparison of eye care in an accident and
      emergency department with a dedicated eye casualty.
AB  - Emergency care for eye complaints is provided both by accident and emergency
      (A&E) departments as well as by dedicated eye casualty departments. This study
      examines the role of each type of department and the quality of eye care
      provided. Significant differences were found between the accident and emergency
      department and the eye casualty department in the history, examination and
      management of eye patients. Most notably, there were significant differences in
      the quality of the assessment in the two institutions. Overall 19% (19/100) of
      A&E records had an inadequate history, compared with 2% (1/50) for eye casualty
      records. Fifty-nine per cent (59/100) of A&E records contained a significant
      examination omission, compared with only 8% (4/50) of eye casualty records. Most
      of the omissions related to a failure to perform an adequate, yet simple, ocular
      examination including failure to record visual acuity. In 44% (44-100) of A&E
      cases visual acuity was not recorded or recorded incorrectly. In comparison
      acuity omissions in eye casualty were present in only 4% (2/50) of cases.

PMID- 7640824
TI  - Out-of-hours radiographs: the effect of resident registrar cover.
AB  - A retrospective study was undertaken to assess the effect of the presence of a
      resident compared with a non-resident registrar on the selection of patients for
      radiography outside normal working hours at a north London district general
      hospital accident and emergency (A&E) department. During periods when the
      registrar was resident there was a significant reduction in the proportion of
      patients referred for radiography.

PMID- 7640825
TI  - The Glastonbury Festival 1993: pattern of attendances and admissions to an NHS
      Trust.

PMID- 7640826
TI  - Support for victims of assaults and domestic violence: are accident and emergency
      departments doing enough?

PMID- 7640828
TI  - Violence towards junior doctors in accident and emergency departments.
AB  - The experience and training of accident and emergency (A&E) junior doctors with
      regard to patient aggression was investigated by use of a telephone
      questionnaire. A total of 114 A&E departments in five different regions in the
      United Kingdom were telephoned. A total of 100 junior doctors answered the
      questionnaire. Verbal aggression had been experienced by 96 of them, 50 had
      received threats and 32 said that patients had tried to assault them. Eighteen
      doctors had been assaulted by patients on a total of 23 occasions. Thirty-two
      doctors admitted that they had been upset after a violent incident, so much so
      that they were preoccupied with it after work. None of those assaulted received
      any counselling and no police charges resulted from the assaults. Only 11 doctors
      had received any training on how to manage aggressive patients, although 88
      believed that it would be useful. The results of this study indicate that
      violence towards junior doctors in A&E is a significant problem. Aspects of this
      problem, including training and support for staff, need to be addressed urgently.

PMID- 7640827
TI  - Out-of-hospital cardiac arrest: two and a half years experience of an accident
      and emergency department in Hong Kong.
AB  - The results are presented of 2 1/2 years of experience of patients with out-of
      hospital cardiac arrests who were resuscitated in an accident and emergency
      department (A&E) attached to an acute district hospital in Hong Kong. Out of 263
      cases of out-of-hospital cardiac arrest as a result of a variety of causes only
      seven patients survived (3%) and among the 135 patients with cardiac aetiology
      only four survived (3%). Ways to improve the outcome for out-of-hospital cardiac
      arrest are discussed.

PMID- 7640829
TI  - Heroin bodypacking.
AB  - Drug smuggling by internal bodily concealment is a well-recognized international
      problem, particularly in view of the difficulty of its detection and the
      potential for large financial gains. This mode of transport can have serious
      medical complications, including drug intoxication--sometimes fatal--as well as
      intestinal obstruction by foreign bodies (FBs). We discuss a case of heroin
      'bodypacking' (the ingestion of heroin filled condoms) with its resultant
      complications. The initial medical management and indications for surgery are
      discussed, and the relevant literature reviewed.

PMID- 7640830
TI  - Dangerous monoamine oxidase inhibitor interactions are still occurring in the
      1990s.
AB  - The clinical course is described of a 28-year-old woman who was severely ill
      following ingestion of a Do-Do tablet (which consists of ephedrine, caffeine and
      theophylline), 24 h after discontinuing phenelzine treatment. Signs and symptoms
      were delayed for 8 h after which she developed encephalopathy, neuromuscular
      irritability, hypotension, sinus tachycardia, rhabdomyolysis and hyperthermia.
      Her illness was complicated by pneumonia and adult respiratory distress syndrome
      (ARDS). The management of monoamine oxidase inhibitor (MAOI) toxicity, which can
      arise from interactions and overdoses, is discussed. It should be remembered
      that, despite the increase in use of alternative and safer antidepressants, MAOI
      interactions still occur and unless they are managed appropriately, are
      potentially fatal. Patients need to be warned that restrictions apply for up to 2
      weeks after stopping the medication, and doctors need to be aware that serious
      interactions can occur in this time period.

PMID- 7640831
TI  - Pharyngeal trauma as a result of blind finger sweeps in the choking child.

PMID- 7640832
TI  - Blunt traumatic pericardial rupture.
AB  - A 28-year-old man presented with left chest, head and limb injuries following a
      road traffic accident (RTA). Increasing haemodynamic instability necessitated an
      emergency left thoracotomy at which a complete rupture of the pericardium and
      herniation of the heart was found. After repair, the patient made an uneventful
      post-operative recovery. The aetiology, investigation and management of this rare
      injury is discussed.

PMID- 7640833
TI  - Self-castration in a transsexual.

PMID- 7640834
TI  - HIV malingering in the accident and emergency department.
AB  - This paper reports a number of cases of patients attending an accident and
      emergency (A&E) department claiming to be HIV positive when they have been tested
      negative and are known to be negative by other departments in the hospital. The
      reasons for these patients claims are not always apparent. These patients may
      place an inappropriate workload on an already busy department. We caution doctors
      working in A&E departments to be vigilant when dealing with patients who claim to
      be HIV positive when there are no clinical or laboratory findings to substantiate
      the claim and we recommend liaison between relevant departments within a hospital
      and the patient's general practitioner (GP) when dealing with these patients.

PMID- 7640835
TI  - Iris dialysis and retinal dialysis caused by coin throwing.
AB  - A 13-year old boy was hit in the right eye by a coin that was thrown at him. He
      presented to the accident and emergency (A&E) department with an oblique corneal
      abrasion, microscopic hyphaema, iris-ciliary body dialysis, commotio retinae with
      retinal haemorrhages and a large retinal dialysis. The limited amount of
      available data in the medical literature suggests that eye injuries as a result
      of coin throwing are serious and should always be referred to an ophthalmologist
      for evaluation.

PMID- 7640836
TI  - Using a metal detector to locate a swallowed ring pull.
AB  - A 48-year-old man accidently swallowed the ring pull from a soft drink can. He
      complained of pain in his chest. Chest radiographs were normal. A metal detector
      emitted a strong response when passed across the front of his chest.
      Oesophagoscopy was carried out and the ring pull was successfully removed. We
      recommend the wider use of metal detectors by accident and emergency (A&E)
      department staff particularly when dealing with patients who have ingested metals
      of low radiodensity.

PMID- 7640837
TI  - Breakfast bar palsy.

PMID- 7640839
TI  - Fracture of the accessory navicular.

PMID- 7640838
TI  - The management of paracetamol overdose by junior doctors.

PMID- 7640840
TI  - Selenops radiata bite.

PMID- 7640841
TI  - Toxic shock syndrome after burns in children.

PMID- 7640842
TI  - Steps are required to improve pre-hospital care.

PMID- 7640843
TI  - Pre-hospital ABCs: getting the right message across!

PMID- 7640844
TI  - Reduction of inappropriate attendances.

PMID- 7640845
TI  - Contamination of clothing in accident and emergency departments.

PMID- 7640846
TI  - Training in major incident planning.

PMID- 7640847
TI  - Head injuries in the accident and emergency department.

PMID- 7640848
TI  - Ecstasy toxicity.

PMID- 7640849
TI  - Long term results of inflatable mammary implants.
AB  - In this retrospective study, the long term results of 167 inflatable mammary
      implants in 77 patients who underwent either breast reconstruction or
      augmentation between 1972 and 1990 were evaluated. All inflatable implants were
      manufactured by Heyer-Schulte/Mentor company, and were equipped with a posterior
      leaf valve (style 1800). The mean follow-up was 9 years (SD = 4.3). Complete
      deflation was found in 23.9% of the implants (22.2% deflation rate from 1972 to
      1984 and 25.5% from 1985 to 1992). The incidence of this complication was
      significantly higher in patients who underwent previous open (p = 0.012) or
      closed (p = 0.038) capsulotomy. Severe contracture of the implant fibrous capsule
      (BAC 3 and 4) was found in 37.6% of the patients. Its incidence increased
      significantly when the postoperative blood loss (assessed by the volume of blood
      collected by suction drainage) exceeded 250 cc (p = 0.025). Neither the site of
      the implant (submuscular/subglandular) nor the indication for surgery
      (reconstruction/augmentation) influenced the rate of severe capsular contracture
      significantly in this retrospective study.

PMID- 7640850
TI  - An experimental model to investigate the dynamics of wound contraction.
AB  - An excisional wound model in the Hooded Lister rat is described. The methods used
      to inflict, measure and characterise the process of wound contraction are
      comprehensively discussed. The model is shown to be reliable, reproducible and
      capable of detecting the effect of systemically administered prednisolone.

PMID- 7640851
TI  - Modifications to the rate of wound contraction by allopurinol.
AB  - The effect of allopurinol (50 mg/kg) on the rate of full thickness excisional
      wound contraction in the Hooded Lister rat was assessed by planimetric and
      histological examinations. Compared with control animals, those treated with
      allopurinol showed a significantly lower coefficient of wound area contraction
      for days 0-7 (p < 0.05) than those of control animals. Histologically, in the
      allopurinol treated wounds the granulation tissue was less cellular but appeared
      to contain more collagen. This inhibition by allopurinol of the contraction phase
      of wound healing associated with an increased quantity of granulation tissue
      suggests that mediation of the process may involve a complex interaction between
      the fibroblasts/myofibroblasts and free radicals.

PMID- 7640852
TI  - Facelifting: an initial eight year experience.
AB  - A retrospective analysis of facelifting experience during the author's initial 8
      years of consultant practice is presented. 137 procedures are reviewed and the
      surgical technique described. 70% were SMAS-platysma lifts, 24% skin only lifts
      and 6% subperiosteal (mask) lifts. Particular attention was paid to
      complications, most common of which was haematoma requiring surgical evacuation
      in 3.6% of patients.

PMID- 7640853
TI  - The fabricated radial forearm flap in pharyngolaryngeal surgery: saliva leakage
      and its prevention.
AB  - Reconstruction of the circular pharyngo-oesophageal defect continues to represent
      a formidable challenge for the head and neck surgeon. The fabricated radial
      forearm flap can provide thin and pliable skin and has potential in this one
      stage reconstructive surgery. However, major problems with this technique are
      saliva leakage, fistula formation and stricture of the oesophageal anastomosis.
      Our experience with this flap for 11 pharyngo-oesophageal reconstructions has
      given us a better understanding of how to prevent these complications. Fistula
      formation and stricture were problems in our first two cases. With the 9
      following cases, prevention of these complications was achieved by positioning
      the T-shaped suture lines of the tubed flap posteriorly. Our results suggest that
      adequate protection of the T-shaped suture lines during fabrication and
      anastomosis of the forearm flap is important in the prevention of saliva leakage.

PMID- 7640854
TI  - The effect of mannitol and anisodamin on the prevention of free radical injury to
      post-ischaemia flaps: an experimental study.
AB  - Rat abdominal skin flaps were subjected to total venous occlusion for 8 h. Five
      minutes before release of the vascular occlusion, mannitol, mannitol plus
      anisodamin, anisodamin or placebo (0.9% normal saline) was administered
      intravenously. Drug treated flaps showed a statistically significant increase in
      the proportion of area surviving (P < 0.001). The combination of mannitol and
      anisodamin was not more effective than either agent alone in increasing the
      proportion of area surviving. The results of biochemical analyses indicated that
      neither mannitol nor anisodamin affected xanthine oxidase activity (p > 0.05) but
      that both agents significantly reduced the increase of malondialdehyde (MDA)
      concentration caused by ischaemia-reperfusion (p < 0.01). Treatment with mannitol
      or anisodamin also prevented the increase of lactate and water content and the
      decrease in glucose content in the island skin flap tissue which occurred on
      reperfusion. The data indicate that mannitol and/or anisodamin have the potential
      to salvage anticipated flap necrosis. It is possible that the mechanism of action
      is inhibition of damage caused by toxic oxygen species and improvement in
      capillary reperfusion.

PMID- 7640855
TI  - Further applications of "bilayer artificial skin".
AB  - A "bilayer artificial skin", composed of an inner layer of collagen sponge and an
      outer silicone layer, was developed by modifying the material reported by Yannas
      and Burke. Since our early results from experimental and clinical use of the
      original version of the "bilayer artificial skin" were reported, several
      improvements have been made in stages to eliminate some drawbacks related to
      disinfection and preservation and to reduce the primary cost of manufacture. The
      latest version of the material was successfully used in 27 sites on 23 patients.
      In this paper, the improvements in the material and the clinical results are
      described.

PMID- 7640856
TI  - Toxicity testing of wound dressing materials in vitro.
AB  - There is a bewildering array of dressing materials available for wound coverage.
      The choice of dressing is often by local custom or practical experience. We
      wished to investigate if different dressings varied in their ability to either
      stimulate or inhibit proliferative activity and differentiation in an in vitro
      test system. We have used a number of test systems for this study. Human dermal
      fibroblast and keratinocyte cultures were used to screen for proliferative and
      cytotoxic effects. A more complex "organotypic" method involving fibroblast
      impregnated collagen gels overlaid with epidermal keratinocytes was used to
      investigate effects on differentiation. Dressings were selected from each of the
      major types available, from simple gauze to hydrocolloids. Of the dressings
      tested, some reduced cell growth rates but the majority showed no major effect on
      proliferation or differentiation. Of those displaying an effect, only one could
      be attributed to cytotoxicity.

PMID- 7640857
TI  - A dorsal flap with lateral digital extensions for palmar web contractures.
AB  - A dorsal flap with lateral digital extensions for correction of palmer web
      contractures following burns is described. Two cases, one with multiple web
      contractures, are presented.

PMID- 7640858
TI  - Multifocal congenital hemangiopericytomas associated with Kasabach-Merritt
      syndrome.
AB  - A newborn male with multifocal congenital hemangiopericytomas complicated by
      Kasabach-Merritt syndrome was treated by excision of a large hemangiopericytoma
      in the right mandibular area. After excision of this lesion, the associated
      consumptive coagulopathy abated. Spontaneous regression of other subcutaneous
      tumours over the thighs and left flank was noted by age 6 months; this
      illustrates the benign course of most congenital hemangiopericytomas. Surgical
      excision of congenital hemangiopericytoma is indicated when there is a coexisting
      consumptive coagulopathy or for the definitive control of large lesions. For
      smaller lesions and in the absence of Kasabach-Merritt syndrome, the benign
      nature and predilection for spontaneous regression of congenital
      hemangiopericytomas render observation as the preferred strategy.

PMID- 7640859
TI  - Intralesional methotrexate in keratoacanthoma of the nose.
AB  - Keratoacanthomas are rapidly growing benign cutaneous neoplasms, usually
      occurring on sun-exposed areas of the body. Although many treatment modalities
      have been described, surgical excision is currently the treatment of choice for
      the majority of keratoacanthomas. Occasionally, however, the size and location of
      these lesions preclude complete excision without extensive reconstruction and/or
      scarring. Two such cases of large keratoacanthoma of the nose were treated
      successfully with intralesional methotrexate. The rapid regression and very
      acceptable final cosmetic result suggest that intralesional methotrexate may play
      a beneficial role in the treatment of these difficult lesions and encourage
      further study of the benefits of this treatment modality.

PMID- 7640861
TI  - Bilateral congenital fatty heel pads.

PMID- 7640860
TI  - A pigmented lesion clinic: analysis of the first year's 1055 patients.
AB  - The Pigmented Lesion Clinic (PLC) at Frenchay Hospital was started in January
      1993 to deal rapidly and effectively with a growing number of referrals of
      suspicious pigmented lesions. Its objectives were to offer expert assessment and
      either reassurance or excision at the first PLC following referral by the
      patient's general practitioner. During 1993, 1055 patients were seen in 37 PLCs
      and 357 excision biopsies were performed. We have compared the Breslow
      thicknesses of malignant melanomas diagnosed from the PLCs with those of all
      other (non-PLC) malignant melanomas referred to our unit over the same period. We
      discuss the development and results of the first year of our PLC and the
      advantages it confers.

PMID- 7640862
TI  - Plastic surgery in Aberdeen.

PMID- 7640863
TI  - Distally based posterior interosseous island flap.

PMID- 7640864
TI  - One-stage repair of hypospadias.

PMID- 7640865
TI  - Formation of porcine hepatocyte spheroids for use in a bioartificial liver.
AB  - Xenogeneic hepatocytes have recently been used in a bioartificial liver device as
      a potential short-term extracorporeal support of acute liver failure. Scaling up
      the system requires large quantities of viable and highly active cells.
      Hepatocytes grown as spheroids manifest higher metabolic activities for longer
      time periods as compared to those in monolayer cultures. Use of hepatocyte
      spheroids for application in a bioartificial liver can possibly alleviate the
      need of scaling up. Porcine hepatocytes when cultured under stirred conditions,
      from multicellular spheroids in a defined culture medium. Spheroids were formed
      24 h after cell inoculation with an efficiency of 80-90% and a mean diameter of
      about 135 microns. Scanning electron microscopy revealed numerous microvilli
      projecting from the entire surface of the spheroids. Transmission electron
      microscopy revealed differentiated hepatocytes which displayed well-developed
      cytoplasmic structures separated by bile canaliculus-like structures. The
      morphological studies show a resemblance between cells in the spheroids and in
      the liver in vivo. Urea-genesis by spheroids was twice as active and was
      sustained for a longer culture period than that by hepatocytes cultured as
      monolayers. Preparation of porcine hepatocyte spheroids in an agitated vessel is
      simple efficient and reproducible. It will allow for preparation of large
      quantities of spheroids to be employed in a bioartificial liver device as well as
      in liver metabolism studies.

PMID- 7640866
TI  - Importance of pH in resuspension media on viability of hepatocytes preserved in
      University of Wisconsin solution.
AB  - The effect of different pH of resuspension media on the viability of hepatocytes
      preserved (for 96 h at 4 degrees C) in University of Wisconsin solution (UW
      solution) was analyzed. After this cold resuspension media storage, we evaluated
      the rewarming step (incubation time 120 min at 37 degrees C) using different pH
      levels (6.80, 7.00, 7.20, and 7.40). Cell viability assessed by trypan blue
      exclusion (TBE) showed a significant difference (p < 0.05) for cells incubated at
      pH = 7.20. For instance, TBE expressed as percent of change was 78.1 +/- 1.4
      compared with cells tested at other pH (pH = 6.80, TBE = 44.2 +/- 9.5; pH = 7.00,
      TBE = 66.5 +/- 1.1 and pH = 7.40, TBE = 62.0 +/- 1.4). We also evaluated the
      capacity of these cells both to maintain potassium content (0.509 +/- 0.230
      microEq. K+/10(6) cells) and to synthesize urea (5.36 +/- 1.81 mumol Urea/10(6)
      cells). These results were compared with those obtained from freshly isolated non
      preserved hepatocytes (0.518 +/- 0.060 microEq. K+/10(6) cells and 5.91 +/- 0.43
      mumol Urea/10(6) cells). The results show that viability is pH dependent and
      suggest that when resuspension media were used, the viability of hepatocytes was
      improved after 96 h of cold storage.

PMID- 7640867
TI  - Collagenase lot selection and purification for adipose tissue digestion.
AB  - Crude Clostridial collagenase (CCC) remains the most widely used enzyme for the
      digestion of tissues prior to cell isolation and culture. CCC contains numerous
      components in addition to specific collagenases and proteases. A chronic problem
      associated with CCC is significant lot variability which occurs with respect to
      the ability of different lots of CCC to digest tissue. We have evaluated numerous
      commercially available samples of CCC for their ability to digest human
      liposuction-derived SC fat. Digestion capacity was evaluated as the ability to
      release endothelial cells from fat as well as the ability of isolated cells to
      adhere to tissue culture plastic. A significant variation in digestion efficacy
      between lots of collagenase was observed. We subsequently purified CCC using a
      partial purification method with dialysis and centrifugation as well as a
      complete purification, using liquid chromatography, to remove all nonspecific
      proteases. While partially purified collagenase retained digestion capacity, pure
      collagenase exhibited reduced digestion capacity. Maximum digestion was achieved
      with pure collagenase when trypsin was added. The use of completely purified
      collagenase with trypsin is advantageous where all components in the enzyme
      digestion mixture must be known.

PMID- 7640868
TI  - Limitations of in-vitro labeling of endothelial cells with indium-111 oxine.
AB  - Indium-111 oxine labeling is widely used as a marker of endothelial cell
      attachment to vascular prostheses. The long term effect of labeling human adult
      endothelial cells (HAECs) with this isotope has not been determined. In this
      study the viability of labeled HAECs, leakage of isotope from labeled cells and
      adherence of circulating isotope to fibronectin coated prostheses were
      investigated over 24 h. The effect of incubation time on labeling efficiency was
      also assessed. There were significant differences in cell viability between the
      labeled and unlabeled groups beyond 4 h (p < 0.005, 2-tailed, unpaired t-test).
      In the control group cell numbers increased by 42% while in the labeled group
      this had decreased by 20% at 24 h. Spontaneous leakage increased with time but
      was maximal in the first 2 h. Adherence of circulating isotope to fibronectin
      coated expanded polytetrafluoroethylene (ePTFE) grafts was minimal but was
      significantly greater to gelatin impregnated Dacron (GEL-SEAL) beyond 1 hour (p <
      0.05). Incubation times greater than 5 minutes during labeling do not
      significantly improve labeling efficiency, and may contribute to toxicity by
      prolonging exposure to oxine. Indium-111 oxine labeling of HAECs is a suitable
      technique for acute studies of endothelial cell kinetics up to 4 h, but its use
      in chronic studies may lead to significant underestimations of cell retention.

PMID- 7640869
TI  - Site for unpurified islet transplantation is an important parameter for
      determination of the outcome of graft survival and function.
AB  - Transplantation of unpurified islets into the liver, unlike that of purified
      islets, causes portal hypertension and coagulopathy. The aim of this project was
      to determine the most suitable alternative site for transplantation of unpurified
      pancreatic islets in autotransplanted dogs. Twenty-five female mongrel dogs were
      divided into 5 groups depending on the site of islet transplantation: liver (3),
      spleen (7), skeletal muscle (5), omental pouch (6), and renal subcapsule (4).
      Pancreatic digestion of the total pancreatectomized specimen was carried out by
      distension of the pancreas with 1.5 mg/mL collagenase suspended in 250 mL Hanks'
      balanced salt solution using a semiautomatic method. The total number of islets
      equivalent isolated from 25 dogs was 90948 +/- 6053. Only islets > 60 microns in
      diameter were counted, and the mean islet equivalent transplanted per kg body wt
      was 6762 +/- 429. Islet function was achieved with transplantation into spleen in
      71%, omental pouch in 50%, and muscle in 20%, but none in the renal subcapsule or
      liver groups. Glucose tolerance test at 30 d showed a mean K Value (decline in
      glucose, %/min) of 1.94 +/- 0.73, 0.79 +/- 0.15 and 1.02 in the splenic, omental
      pouch and muscle groups, respectively. All animals in the liver group, 2 from the
      splenic group, and 2 from the renal subcapsule group died of diffuse bleeding.
      Four out of 5 dogs in the muscle group developed necrosis at the site of
      transplantation and the islets never functioned. This study demonstrates that in
      dogs, spleen and omental pouch appear to be suitable sites for transplantation of
      unpurified islets.

PMID- 7640870
TI  - Embedded-culture of pancreatic beta-cells derived from transgenic mouse
      insulinoma as a potential source for xenotransplantation using a diffusion
      chamber.
AB  - Embedded-culture of pancreatic beta-cells derived from a transgenic mouse
      insulinoma (MIN6 cells) was studied in vitro and in vivo. The MIN6 cells were
      enmeshed in an agarose-PVMA-collagen matrix for long-term maintenance. The cells
      formed islet-like cell clusters (ICCs) in the mixed matrix. When 10 mmol/L
      nicotinamide was added to these cultures the cells secreted insulin in response
      to various concentrations of glucose, whereas the untreated control cells were
      unresponsive. Both control and nicotinamide-treated MIN6 cells exhibited normal
      beta-cell function for up to 35 days in the mixed matrix, and the cells were much
      better preserved with nicotinamide than without it. MIN6 cells were suspended in
      the mixed matrix with nicotinamide and transferred into diffusion chambers to
      create a bio-artificial endocrine pancreas (Bio-AEP). In streptozotocine-induced
      diabetic rats with implanted Bio-AEP but without any immunosuppressants, a return
      to normoglycaemia was observed for up to 12 wk or more after transplantation. Our
      results indicate that nicotinamide-treated MIN6 cells embedded in a mixed matrix
      should be useful for the study of xenotransplantation and the development of a
      bioartificial endocrine pancreas.

PMID- 7640871
TI  - Immunosuppressive effect of 2'-deoxycoformycin (Pentostatin) for rat islet
      allotransplantation.
AB  - Adenosine deaminase (ADA) is an important enzyme for proper function of
      lymphocytes and congenital absence of ADA results in a form of severe combined
      immunodeficiency syndrome. 2'-Deoxycoformycin (Pentostatin, DCF) irreversibly
      inhibits ADA and therefore has been suggested as an immunosuppressive drug. The
      present study evaluated the immunosuppressive effect of DCF for islet
      allotransplantation in rats. Isolated islets (1,500 islets) from Lewis rats were
      transplanted into the kidney subcapsular space of streptozotocin-induced diabetic
      Wistar-Furth rats. DCF was administered IP either as a single injection at 1
      mg/kg/wk, 1 mg/kg twice weekly, 5 mg/kg/twice weekly or 1 mg/kg/day, or as a
      continuous infusion at 0.8 or 1 mg/kg/day. Daily administration of DCF at 0.8
      mg/kg in both methods, single daily injection or continuous infusion, resulted in
      a lymphopenia and a decrease in concanavalin A stimulation of splenic
      lymphocytes. However, DCF (in all doses) was not effective in preventing islet
      allograft rejection as evaluated by measuring the duration of normoglycemia
      following islet transplantation and by microscopic examination of the islet
      grafts. In fact, the duration of normoglycemia following islet transplantation
      was 7.5 +/- 0.9 and 9.0 +/- 1.0 days in rats receiving DCF in single daily
      injection or continuous infusion, respectively. This was not significantly
      different from control nontreated transplanted rats (8.5 +/- 0.7 days).
      Increasing the dose of DCF to 1 mg/kg, administered by continuous infusion,
      resulted in 100% mortality. For comparison, cyclosporine A (20 mg/kg, IP daily
      injection for 14 days) prolonged islet allograft survival to 27.3 +/- 1.5 days (p
      < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7640872
TI  - Transplantation of mesencephalic cell suspensions from wild-type and heterozygous
      Weaver mice into the denervated striatum: assessing the role of graft-derived
      dopaminergic dendrites in the recovery of function.
AB  - The Weaver (wv) mutation leads to a loss of mesencephalic dopamine cells and
      nigrostriatal dopamine axons in homozygosity (wv/wv) and to a deficiency of
      nigral dopaminergic dendrites without a concomitant loss of dopamine cell somata
      or axons in heterozygosity (wv/+). Previous studies have shown that grafts of
      foetal dopamine cells from wild-type (+/+) donors can survive when implanted into
      the wv/wv striatum, supply both an axonal and a dendritic innervation to the
      host, establish synaptic connections with host striatal neurons, and bring about
      a functional recovery evidenced by rotational asymmetry tests. The aims of the
      present study were to examine whether wv/+ dopamine cells maintain a "dendrite
      poor" phenotype after transplantation to the denervated striatum, and to compare
      their functional effects with those of wild-type (+/+) grafts in reversing
      amphetamine-induced turning behaviour. To that end, +/+ and wv/+ ventral
      mesencephalic tissue (dissected out from E10-E12 foetal mice and made into a cell
      suspension by enzymatic and mechanical dissociation) was stereotactically grafted
      into the right striatum of either wv/wv hosts or +/+ hosts subjected in advance
      to 6-OHDA lesions of the right substantia nigra. Viability and morphology of
      grafted neurons were assessed by tyrosine hydroxylase immunocytochemistry on
      serial sections of the host forebrains. Dopamine cell bodies survived in
      comparable numbers in the grafts regardless of donor genotype; however, grafts of
      either genotype contained fewer dopaminergic cells when they were hosted in the
      wv/wv striatum as compared to the striatum of +/+ mice with 6-OHDA lesions.
      Despite the survival of cell somata, the dendritic arborisation of wv/+ cells was
      strikingly poorer than that of +/+ cells in grafts placed into both host types,
      most likely reflecting their in situ phenotypic abnormality. Recipient wv/wv mice
      with +/+ and wv/+ grafts exhibited 88% and 83% left rotations, respectively; 6
      OHDA hosts with +/+ and wv/+ grafts showed 178% and 165% reversals of asymmetry,
      respectively. The differences between the effects of +/+ and wv/+ grafts were not
      statistically significant.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7640873
TI  - Isolation and manipulation of rostral mesencephalic tegmental progenitor cells
      from rat.
AB  - A technique for isolating mitotic progenitor cells from the embryonic rostral
      mesencephalon is described. Culture of the progenitor cells in complete media
      with subsequent staining for neuron specific enolase (NSE) revealed that only
      0.6% of the cells were NSE immunoreactive. Co-culturing the progenitor cells with
      established striatal cultures did not result in conversion of any of the cells to
      the dopamine neuron phenotype (tyrosine hydroxylase immunoreactive (THir)
      neurons). In contrast, co-culture of progenitor cells with established
      mesencephalic cultures produced a statistically significant, and in some cases
      (three of twelve), dramatic increase in the number of THir cells. The THir cells
      that were present had more pronounced process extension than those observed in
      mesencephalic mono-cultures. Culturing progenitor cells in transwell baskets that
      were continuously exposed to media but physically separated from established
      mesencephalic cultures growing underneath the baskets led to the conversion of
      only a few progenitor cells to THir neurons in four of twelve transwell studies
      suggesting that cell-cell contact between progenitor cells and mesencephalic
      cells is required for the conversion. This co-culture technique also increased
      the number of THir neurons in the mesencephalic cultures although the increase
      was not profound enough to explain the increase observed in traditional co
      culture. These data suggest that mitotic progenitor cells can be isolated from
      fetal rat tissue and successfully converted to the dopamine neuron
      phenotype.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7640874
TI  - Immunostaining of human amniotic epithelial cells: possible use as a transgene
      carrier in gene therapy for inborn errors of metabolism.
AB  - Immunoreactivity of human cultured amniotic epithelial (AE) cells was
      investigated to evaluate the possible use of these cells as a transgene carrier
      in gene therapy for inborn errors of metabolism. AE cells were prepared and
      cultured by the methods described previously. Flow cytometry analysis revealed
      that these cells did not express any class II antigen at all on their surfaces.
      But the class I antigen was slightly expressed on their surfaces.
      Immunoperoxidase staining was slightly positive as to the class I antigen but not
      to the class II antigen at all. pSV-beta-galactosidase was transfected into AE
      cells by means of electroporation, followed by staining of the cells with X-gal.
      Several cells in 60 mm dish expressed beta-galactosidase activity. The possible
      gene transfer of beta-galactosidase into cultured AE cells may suggest that these
      cells could be used as a transgene carrier in gene therapy for inborn errors of
      metabolism.

PMID- 7640875
TI  - Effect of beta-carotene supplementation on the human sunburn reaction.
AB  - Beta-carotene, a quencher of excited species such as singlet oxygen and free
      radicals, has been reported to protect against cutaneous photodamage, including
      sunburn acutely and photocarcinogenesis chronically. The present double blind
      placebo-controlled study examines the effect of beta-carotene supplementation on
      the human sunburn response and specifically on the induction of sunburn cells at
      the time of peak reaction intensity (24 h) after a single solar simulated light
      exposure 3 times the individually determined minimal erythema dose (MED).
      Administered orally either as a single 120 mg dose to dietarily restricted
      subjects or for 23 d as a daily 90 mg supplement to subjects on standard diets,
      beta-carotene increased plasma and skin levels of beta-carotene compared to both
      pretreatment levels and placebo-treated controls, but provided no clinically or
      histologically detectable protection against a 3 MED sunburn reaction. Thus,
      these data suggest that oral beta-carotene supplementation is unlikely to modify
      the severity of cutaneous photodamage in normal individuals to a clinically
      meaningful degree.

PMID- 7640876
TI  - Reduced cytokine production in response to stimulation with dust mite antigen
      after cyclosporin A treatment of atopic dermatitis.

PMID- 7640877
TI  - Proto-oncogenes and oncogenes in epidermal neoplasia.
AB  - This review briefly will focus on the role of selected proto-oncogenes and their
      activated forms during the regulation of cell proliferation, cell death and tumor
      formation in the epidermis. In addition, the multiple and complex functions of
      these proteins in normal as well as transformed cells will be discussed.

PMID- 7640878
TI  - Incorporation of 15-hydroxyeicosatrienoic acid in specific phospholipids of
      cultured human keratinocytes and psoriatic plaques.
AB  - 15-hydroxyeicosatrienoic acid, 15-HETrE, the 15-lipoxygenase product of
      dihomogammalinolenic acid (DGLA), can inhibit the biosynthesis of the
      proinflammatory eicosanoids leukotriene B4 (LTB4) and 12-hydroxyeicosatetraenoic
      acid (12-HETE). The purpose of the present study was to investigate the
      incorporation of [14C]15-HETrE in specific membrane phospholipids of cultured
      human keratinocytes in vitro. [14C]15-HETrE was rapidly incorporated into
      keratinocytes. When a plateau was reached after 3 hours, 15% of the added
      radioactivity was incorporated into lipids; 96.5% into phospholipids (PL) and
      3.5% into neutral lipids (NL). Within the phospholipid classes, [14C]15-HETrE
      showed selectivity for incorporation into phosphatidylinositol (PI). The mean
      proportion of [14C]15-HETrE in the PI, phosphatidylcholine (PC) and
      phosphatidylethanolamine (PE) was 83.2%, 8.5% and 8.3%, respectively. We then
      investigated the incorporation of 15-HETrE in epidermal phospholipids of
      psoriatic skin intralesionally injected with 15-HETrE. Four patients took part in
      the study. In each patient four identical plaques were injected with 0.65 ml of
      2.0 microM, 6.2 microM, 18.6 microM of 15-HETrE (0.4 micrograms, 1, 2 micrograms
      and 3.6 micrograms respectively) or 0.65 ml of 0.88% NaCl twice a week. After 3
      wk keratome biopsies were obtained from the treated plaques. Phospholipids
      extracted from the skin biopsies were separated into major classes by two
      dimensional thin layer chromatography. 15-HETrE was then released from specific
      phospholipids after treatment with phospholipase A2 and identified by reverse
      phase and straight phase high performance liquid chromatography. There was a dose
      dependent incorporation of 15-HETrE into the specific phospholipids PI and PC.
      When expressed as ng 15-HETrE/micrograms phospholipid phosphate, 15-HETrE
      accumulated preferentially in PI.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7640879
TI  - Effect of azelaic acid on melanoma cells in culture.
AB  - Using a clonogenic assay in vitro, it has been shown that exposure to azelaic
      acid (1-100 mM) for 24 hours has a dose-dependent effect on the survival of the
      colony-forming ability of murine (B16) and human (HMB2, and SK23) melanoma cells
      as compared with a non-melanotic non-tumoral Chinese hamster cell line (CHO).
      Both human cell lines were more sensitive to the diacid than the murine cells,
      and the HMB2 cells were more sensitive than the SK23 cells. These differences may
      be partly correlated with differences in pigmentation and doubling times between
      the three melanoma cell lines. The two human lines were more pigmented than the
      B16, and the SK23 more than the HMB2; the human lines had a longer doubling time
      than the others.

PMID- 7640880
TI  - Tyrphostins suppress the growth of psoriatic keratinocytes.
AB  - Tyrosine kinase inhibitors of the tyrphostin family which block EGF receptor
      kinase are reported to arrest the growth of psoriatic keratinocytes in vitro.
      Three tyrphostins with the potency ratio AG555 >> AG18 >> AG814 were found to
      arrest growth with no adverse cytotoxic effects. The potency ratio to inhibit
      keratinocyte proliferation follows their potency to inhibit EGF receptor kinase
      activity in vitro. These compounds represent novel leads for the therapy of
      psoriasis.

PMID- 7640881
TI  - Separation of epidermis from dermis in the rhesus monkey.
AB  - Effective methods exist for separating epidermis from dermis for many species;
      however, a simple and effective skin separation method for non-human primates is
      not available. This investigation describes an easy and reliable method for
      separating epidermis from dermis in Rhesus monkeys. Skin was shaved and washed
      prior to necropsy. Skin samples were placed on cardboard and then in Whirl-Pak
      bags, frozen on dry ice and stored at -70 degrees C. Just prior to the separation
      procedure, Whirl-Pak bags were returned to dry ice storage. Immediately after
      removal from dry ice, each closed Whirl-Pak bag was placed into a waterbath
      maintained between 60 and 67 degrees C. After 2 minutes, the Whirl-Pak bag was
      removed from the waterbath, opened and the skin surface of the application site
      was gently scraped with a scalpel blade to remove the epidermis. Effectiveness of
      removal was verified by histologic examination of the remaining dermal samples.

PMID- 7640882
TI  - Regulation of CRABP II mRNA expression in human keratinocytes.
AB  - Cultured human neonatal keratinocytes were used to study the mechanisms and
      factors involved in the regulation of CRABP II gene expression. Post-confluent,
      relatively differentiated keratinocyte cultures had higher levels of CRABP II
      mRNA, but nuclear run-on experiments detected no sustained increase in CRABP II
      gene transcription rate between pre-confluent and post-confluent cells. Also, our
      studies could detect no change in the long half-life (> 32 hours) of this message
      in pre- and post-confluent cultures. Hydrocortisone was found to reduce the
      confluency-related increase in CRABP II mRNA in keratinocyte cultures. Because
      corticosteroids are known to reduce the effect of various cytokines, a series of
      epidermal cytokines were examined for a modulating effect on CRABP II mRNA
      content in cultured keratinocytes. IL1 alpha produced the greatest increase and
      IL6 the strongest reduction in the level of this message in cells grown in serum
      free, defined medium. These data support a role for CRABP II in the proliferation
      and differentiation of human keratinocytes and suggest that epidermal cytokines
      may at least in part regulate the expression of the CRABP II gene at the mRNA
      level.

PMID- 7640883
TI  - Functional MR imaging. Capabilities and limitations.
AB  - Functional MR imaging techniques are showing promise in the detection and
      assessment of cerebral pathophysiology and, more recently, in the
      characterization and regional mapping of distinct human cognitive functions, such
      as vision, motor skills, language, and memory. This article discusses the
      mechanism of functional MR imaging, its capabilities, and its limitations.

PMID- 7640884
TI  - Functional MR imaging of perceptual and cognitive functions.
AB  - Functional MR imaging using the blood oxygen level dependent technique as an
      endogenous contrast agent localizes eloquent cortex when stimulated by a variety
      of motor or sensory tasks. To date, visual, motor, speech, and cerebellar studies
      have been conducted, revealing significant information regarding cortical
      localization and control of various functions. The technique is also an important
      management tool for localizing eloquent cortex contiguous to a tumor or
      arteriovenous malformation, so that injury can be avoided if ablation of the
      lesion is contemplated.

PMID- 7640886
TI  - Magnetoencephalography and magnetic source imaging. Capabilities and limitations.
AB  - The advent of large-array superconducting biomagnetometer systems, including
      sophisticated operating and data processing electronics, has enabled practical
      patient studies evaluating the potential contribution of magnetoencephalography
      to clinical medicine. The superimposition of sources localized magnetically onto
      anatomic images, referred to as magnetic source imaging, has allowed physicians
      to conduct this evaluation in the content of their customary medical practice.
      This article summarizes the basic technology of magnetoencephalography and
      magnetic source imaging and includes brief descriptions of the various
      applications that are being studied with these new sensor systems, some of which
      are discussed in subsequent articles.

PMID- 7640885
TI  - Functional MR imaging correlations with positron emission tomography. Initial
      experience using a cognitive activation paradigm on verbal working memory.
AB  - The most established functional MR imaging technique for activation studies
      relies on a T2*-weighted contrast. This signal arises primarily from a blood
      oxygen level dependent contrast generated by an imbalance between the increase in
      regional cerebral blood flow and oxygen metabolism in the brain during
      activation. As predicted by theory, the percentage signal changes observed in
      functional MR imaging experiments are considerably smaller than those detected by
      positron emission tomography, which directly measures regional cerebral blood
      flow as an index of neuronal activity. Cross-validation of functional MR imaging
      with an established technique such as positron emission tomography would be
      extremely valuable for determining the correlation between functional MR image
      signal change and regional cerebral blood flow change and for assessing the
      sensitivity of the functional MR imaging technique. The authors report on such
      cross-validation experiments in three subjects challenged with a verbal working
      memory task and show that satisfactory replication of positron emission
      tomography results with functional MR imaging was achieved in two subjects.
      Limitations owing to magnetic field strength used and single-slice sampling may
      have contributed to the lack of signal detection in the case where no reliable
      activation pattern was detected with functional MR imaging.

PMID- 7640887
TI  - Applications of magnetic source imaging to presurgical brain mapping.
AB  - This article highlights the patient benefits of noninvasive presurgical mapping
      using magnetic source imaging, discusses magnetic source imaging in terms of its
      practical implementation and current limitations in mapping the human cerebral
      cortex, and illustrates the use of magnetic source imaging in ongoing clinical
      studies. An overview of preliminary research studies that have attempted to
      evaluate the accuracy and cost-effectiveness of magnetic source imaging in
      presurgical mapping is also provided.

PMID- 7640888
TI  - Applications of magnetic source imaging in evaluation of candidates for epilepsy
      surgery.
AB  - Epilepsy was the first clinical entity to which magnetic source imaging was
      applied; however, the technology available severely limited early studies. The
      introduction of large-array magnetic source imaging systems has enabled striking
      advances in the application of magnetic source imaging in epilepsy surgery
      programs. The superimposition of functional localization of epileptic sources on
      anatomic images from MR imaging or computed tomography allows precise definition
      of the area and extent of epileptogenic tissue for possible resection.
      Concordance of magnetic source imaging indications with other noninvasive studies
      may reduce that need for invasive studies in certain patient populations.

PMID- 7640889
TI  - Pediatric magnetic source imaging.
AB  - Magnetic source imaging has changed the perspective of managing pediatric
      patients with epilepsy since its introduction into clinical imaging in the
      pediatric population. Magnetic source imaging can be important in understanding
      pediatric functional neuroanatomy and for epileptic surgery in children with
      intractable seizures. The use and efficacy of magnetic source imaging for
      surgical planning and patient management is demonstrated by case reports
      presented in this article.

PMID- 7640890
TI  - Purification and properties of wall-bound endo-1, 4-beta-glucanase from
      suspension-cultured poplar cells.
AB  - A wall-bound endo-1, 4-beta-glucanase (EC 3.2.1.4) was obtained from a
      preparation of the cell walls of suspension-cultured poplar cells and purified to
      electrophoretic homogeneity by cation-exchange, hydrophobic, and gel-filtration
      chromatography. The molecular mass was estimated to be 47 kDa by SDS-PAGE and 48
      kDa by gel filtration on Superdex 200 pg. The isoelectric point (pI) was 5.6. The
      purified enzyme catalyzed the endo-hydrolysis of carboxymethylcellulose with an
      optimal pH of 6.5, a Km of 1.2 mg ml-1, and a Vmax of 280 units. The purified
      enzyme specifically hydrolyzed the 1, 4-beta-glucosyl linkages of
      carboxymethylcellulose, phospho-swollen cellulose, lichenan, xylan and
      xyloglucan. The activity of the enzyme was strongly stimulated by cysteine-HCl.
      The N-terminal sequence of the enzyme was similar to that of an extracellular
      endo-1, 4-beta-glucanase found in suspension cultures of poplar cells and some
      homology was recognized to avocado fruit-ripening and bean abscission endo-1, 4
      beta-glucanases.

PMID- 7640891
TI  - Cytosolic aconitase participates in the glyoxylate cycle in etiolated pumpkin
      cotyledons.
AB  - Two different aconitases are known to be expressed after the germination of oil
      seed plants. One is a mitochondrial aconitase that is involved in the
      tricarboxylic acid cycle. The other participates in the glyoxylate cycle, playing
      a role in gluconeogenesis from stored oil. We isolated and characterized a cDNA
      for an aconitase from etiolated pumpkin cotyledons. The cDNA was 3,145 bp long
      and capable of encoding a protein of 98 kDa. N-terminal and C-terminal amino acid
      sequences deduced from the cDNA did not contain mitochondrial or glyoxysomal
      targeting signals. A search of protein databases suggested that the cDNA encoded
      a cytosolic aconitase. Immunoblotting analysis with a specific antibody against
      the aconitase expressed in Escherichia coli revealed that developmental changes
      in the amount of the aconitase were correlated with changes in levels of other
      enzymes of the glyoxylate cycle during growth of seedlings. Further analysis by
      subcellular fractionation and immunofluorescence microscopy revealed that
      aconitase was present only the cytosol and mitochondria. No glyoxysomal aconitase
      was found in etiolated cotyledons even though all the other enzymes of the
      glyoxylate cycle are known to be localized in glyoxysomes. Taken together, the
      data suggest that the cytosolic aconitase participates in the glyoxylate cycle
      with four glyoxysomal enzymes.

PMID- 7640892
TI  - Purification and characterization of a vegetative lytic enzyme responsible for
      liberation of daughter cells during the proliferation of Chlamydomonas
      reinhardtii.
AB  - A vegetative lytic enzyme (VLE) of Chlamydomonas reinhardtii mediates digestion
      of the cell walls of mother cells (sporangia) to allow release of daughter cells
      after miotic cell division in the vegetative cell cycle. This enzyme is secreted
      into the culture medium concurrently with the appearance of daughter cells in
      synchronized cultures. Using an assay that monitors digestion of the mother cell
      wall, we purified VLE by ion-exchange and gel-filtration chromatography from the
      medium of synchronized cultures. The purified enzyme was a basic glycoprotein
      with an apparent molecular mass of 120 kDa on gel filtration and 130 kDa on SDS
      PAGE. Thus, VLE appeared to behave as a monomer. The enzyme acted specifically on
      the mother cell wall and was unable to digest the cell walls derived from single
      vegetative cells. The enzymatic activity was inhibited by PMSF, p-APMSF, TLCK,
      HgCl2, iodoacetate, EGTA, EDTA and 1, 10-phenanthroline. VLE cleaved several
      synthetic model peptides on the carboxyl side of a Lys or Arg residue, indicating
      that it is a protease that acts on protein in the mother cell wall in vivo to
      release the daughter cells.

PMID- 7640893
TI  - Presence of a chloroplast DNA sequence in an autonomous circular DNA molecule in
      cultured rice cells (Oryza sativa L).
AB  - Sequence analysis of twelve DNA fragments, which had previously been found to be
      extensively amplified in suspension-cultured rice cells, revealed that two of
      them, isolated on plasmids designated pE10 and pE11, have sequences identical to
      distinct regions of chloroplast DNA (ct-DNA). Both sequences are part of an
      extrachromosomal circular DNA molecule (ECD). The molecular structure of the ECD
      was investigated by a combination of restriction analysis, standard and pulsed
      field gel electrophoresis, hybridization with ct-DNA probes and amplification by
      the polymerase chain reaction in the presence of oligonucleotide primers
      homologous to selected regions of rice ct-DNA. The results showed that a
      continuous and unrearranged stretch of ct-DNA from the long single-copy region,
      of at least 28 kbp in length, is present in the ECD. It was estimated that the
      number of copies of the ECD in cultured cells was almost equivalent to that of ct
      DNA molecules in rice leaves, while the ratio of ECD to ct-DNA molecules in the
      cultured cells was approximately 200:1.

PMID- 7640894
TI  - [Ebola 1995: history repeats itself].

PMID- 7640895
TI  - [Ebola, a tranquil river in the heart of Africa].

PMID- 7640896
TI  - [From tropical ophthalmology to public health ophthalmology].

PMID- 7640897
TI  - [The use of ivermectin in the control of onchocerciasis].
AB  - Onchocerciasis is an infection with the nematode Onchocerca volvulus. The main
      clinical symptoms are caused by the microfilariae. They include ocular lesions
      leading to blindness. Onchocerciasis is widely distributed in Africa from the
      Sahara to the southern tip, and is also found in some areas of South and Central
      America. Ivermectin was shown to be an effective treatment in the early 1980's,
      and is safe and better tolerated than diethylcarbamazine. We report the results
      of ivermectin treatment of onchocerciasis, and various features of the control
      obtained by large-scale ivermectin treatment programs. In large-scale programs,
      ivermectin (150 micrograms/kg) is administered once a year. This dose paralyses
      the microfilariae, such that they are carried away by the lymph to the lymph
      nodes where they are destroyed. This dose thereby reduces the load of
      microfilaria by 90%. The effects of a dose of ivermectin last about two or three
      years, and the lesions in the anterior segment of the eye can be cured or
      substantially reduced. Regular treatment prevents severe lesions of the posterior
      segment of the eye. The effects of repeated treatment on lesions of the retina
      are currently under investigation. Frequent doses of ivermectin prevent the
      development of embryo parasites in the females, and reduces the number of adults
      by attrition. Large-scale treatment programs reduce the transmission of the
      parasite by its vectors. There are several problems impeding large-scale
      treatment programs. Choosing patients for priority treatment requires expensive
      and sometimes aggressive methods of diagnosis. Thus new techniques for the
      identification of communities in which onchocerciasis is a serious public health
      problem are required. The choice of strategies for distribution, to optimize the
      cost, benefit ratio and feasibility, remain controversial. Wide distribution by
      mobile teams is effective, but expensive. Active distribution by trained
      community distributors is a cheaper potential alternative. Clinic-based or
      passive distribution requires the population to present to be able to obtain
      ivermectin. Thus, although cheap, this approach is generally poorly effective. A
      further complication is the clearly defined criteria on which these methods
      should be evaluated.

PMID- 7640898
TI  - [Xerophthalmia. Identification of populations at intermediate risk].
AB  - In developing countries, vitamin A deficiency (VAD) is a major contributor to
      child blindness and is associated with increased mortality. We assessed the
      vitamin A status of a Sahelien population and evaluated the correlation between
      the various criteria used to score xerophthalmia. The survey was carried out
      between June 1992 (the end of the dry season) using a representative sample of
      906 children between the ages of 3 and 7 years in the district of Douentza. The
      population sample was selected by a two stage cluster sampling method (villages
      and then households). Vitamin A status was evaluated using clinical, histological
      and nutritional criteria. Clinical examination included testing for night
      blindness (XN), Bitot's spots (X1B) and corneal scars (XS). The Impression
      Cytology with Transfer (ICT) test described by Amedee-Manesme was used for
      histological analysis. Cases of follicular trachoma were recorded because of the
      possible influence of active trachoma on the findings of the ICT test.
      Nutritional status was determined by measuring the height for weight ratio
      according to the National Center for Health Statistics criteria. The prevalence
      of XN was 2.7% (1.6-3.7), significantly higher than the WHO threshold for a
      public health problem. The prevalence of X1B was 0.5% (0.1-1.2), and no corneal
      scars were detected. 31.7% of the children were suffering from malnutrition, but
      malnutrition did not correlate with any of the ophthalmological indicators of a
      public health problem. Among the 842 readable ICT tests, 265 were abnormal (31.4%
      of the total, 28.2-34.5). This incidence of abnormal results was unexpectedly
      low, in the light of the clinical results, and well below the threshold value of
      50% suggested by Carlier.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7640899
TI  - [A survey of the prevalence and causes of eye disorders in primary school
      children in Antananarivo].
AB  - To assess the prevalence and causes of ocular abnormalities in children, we
      performed a cross-sectional survey with cluster sampling in Madagascar in
      Antananarivo primary schools in October 1994. Our other aim was to sensitize the
      sanitary authorities and the students of ophthalmology to the notion of public
      health ophthalmology in a country where a national blindness prevention program
      is being established. 1,081 children aged from 8 to 14 years (mean age 10.6
      years) were examined. 51, or 4.7%, were diagnosed as having ocular abnormalities.
      These abnormalities were distributed as follows: 22 cases or 2% of the sample had
      refractive errors including 0.74% with myopia of less than 6 dioptrics, 0.18%
      with myopia of more than 6 dioptrics, 0.83% with hypermetropia of less than 6
      dioptrics, and 0.28% with hypermetropia of more than 6 dioptrics; 15 cases or
      1.4% of the sample had unilateral amblyopia including 0.9% with anisometropia,
      0.37% with strabismus, and 0.09% with macular pathology; 8 cases or 0.74% of the
      sample had strabismus without amblyopia; and 6 cases or 0.57% of the sample had
      simple medical pathology. The results showed that 29 children were supposed to
      have an optic correction, including surgical treatment for 12 and medical
      treatment for 6. The same low frequencies of ocular abnormalities, mainly
      concerning refractive errors, were found in the literature. However, children
      suffering from important visual impairment do not attend school, and we cannot
      generalize the above results for the whole population.

PMID- 7640900
TI  - [Health indicators of a population in an agro-industrial complex of southern
      Cameroon].
AB  - An agro-industrial program involving sugar cane farming was established in
      Mbandjock (Cameroon) in the 1960's. We studied the impact of this development
      project on the health of the population by determining the prevalence and
      distributions of the major parasitic diseases according to district, ethnic
      origin, age and sex. Three main conclusions can be drawn. First, in the study
      area, economic development was not associated with deteriorating health
      conditions. Indeed, the incidence of parasitic disease was lower in Mbandjock
      than in surrounding areas. Second, imported diseases (loaiasis and
      schistosomiasis for example) did not develop locally despite the large population
      concentrations created by the implantation of the agro-industrial complex. Third,
      endemic parasitic diseases (malaria, onchocerciasis and intestinal infection by
      helminths or protozoan) were found only in a few districts. Thus, integrated
      control measures should be taken in these areas as a priority.

PMID- 7640901
TI  - [An outbreak of Shigella dysenteriae type 1 dysentery in a refugee camp in
      Rwanda].
AB  - As a consequence of the civil war that devastated Burundi in October 1993, more
      than 300,000 refugees settled in the neighboring country of Rwanda. We describe
      the outbreak of dysentery due to Shigella dysenteriae type 1 (Sd1) that developed
      in Nzangwa, a camp hosting some 20,000 Burundese refugees. Between November 17,
      1993 and March 10, 1994, 6,122 cases of bloody diarrhea were notified by the
      health information system of the camp. The overall attack rate was 32.3%, and the
      fatality rate was 3.8%. Children under five years of age were the most affected
      group of the population. All dysentery cases were treated with nalidixic acid for
      5 days. The compliance assessment showed that less than 50% of the ambulatory
      patients completed the 5-day regimen. From 35 stool samples obtained from the
      refugees, seven Sd1 strains were isolated, of which three were multi-resistant to
      nalidixic acid. These results confirmed the morbidity and mortality of Sd1
      outbreaks in the displaced populations of Central Africa. We also emphasize the
      difficulties in implementing effective prevention measures and appropriate case
      management strategies in this environment. To improve the management of patients
      in large Sd1 outbreaks with limited resources, we devised a clinical
      classification of cases according to the risk of dying.

PMID- 7640902
TI  - [Larval Clinostomum infection of cichlid fish in the lake of Kompienga in Burkina
      Faso: a menace to haleutic exploitation and public health].
AB  - Clinostomum sp. is a trematode, a parasitic worm, of which the larva infest a
      number of species of wild fish. In intertropical Africa and particularly in
      artificial lakes in the east of Burkina Faso, the infestation is especially
      observed in the cichlids fish. Because cichlids constitute 80 to 90% of the fish
      catches, enzootic infestation could infringe upon the fisheries, and also
      adversely affect public health. For this epidemiological study conducted during
      the first three quarters of 1994, we examined a total of 932 cichlids, a mix of
      all species. Prevalence (Pr) and intensity (I, number of parasites per fish) were
      the two indicators of the infestation level. 387 fish were carriers of the
      parasite, comprising 41.5% of the total. Differences were observed between the
      species of cichlids. Oreochromis niloticus was the most infested (Pr, 56%; I,
      17), followed by Sarotherodon galilaeus (Pr, 44%; I,6); and Hemichromis fasciatus
      (Pr, 20%; I, 5). In 89% of the carriers, the parasite was localized on the
      internal face of the operculum and in the pericardial septum, compared to 11% of
      the localizations in subcutaneous and muscular tissues. These last two
      localizations render the fish repugnant, and can cause the fresh fish to be
      rejected. If the parasitized fish is not rejected and then insufficiently cooked,
      as occurs at public grills with multitudes of consumers, the living parasite can
      penetrate and stay in the upper digestive tract and constitute a threat for
      consumer health.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7640904
TI  - British Society for Rheumatology, Heberden Round, Keele, 13-15 September 1995.
      Abstracts.

PMID- 7640903
TI  - [79 cases of invasive cancer of the cervix uteri in the Department of Oncology in
      Antananarivo. Can diagnostic delays be improved?].
AB  - The frequency of invasive cervical carcinoma in Western countries is currently
      decreasing. The development of methods of early diagnosis has improved the
      prognosis of the disease. In Madagascar, like in other African countries,
      invasive cervical carcinoma is the first genital cancer affecting women. The
      diagnosis comes late. Actions can be taken to improve the prognosis through early
      diagnosis of invasive cervical carcinoma. Our purpose was to analyze the main
      causes leading to these delays in diagnosis and to evaluate possibilities for
      improvement. This study was retrospective, consecutive and open wide not random,
      dealing with 79 cases of invasive cervical carcinoma, all confirmed by a
      histological examination, picked from the Department of Oncology at Antananarivo
      within a period of 24 months from the 1st of January 1990 through the 1st of
      January 1992. The Department of Oncology at Antananarivo is the only anti-cancer
      center available on the island. The position for an oncologist was occupied form
      1984 to 1988 by a French doctor under the Technical Cooperation Agreement with
      France. Since then, no oncologist has been practicing in Madagascar. We evaluated
      the different reasons that could explain the delays in diagnosis and suggested
      possible actions to remedy the problem. We selected medical, human and technical,
      as well as geographical and social criteria for evaluation. Diagnosis was delayed
      too much (on average, about 8.48 +/- 7.12 months), possibly due to the above
      mentioned criteria.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7640905
TI  - Biomarkers used for the assessment of health hazards in populations living in the
      vicinity of communal and industrial waste dump sites.
AB  - The measure of individual hazard from exposure to environmental toxicants are the
      biomarkers which are indices of abnormalities within different biological systems
      that may be induced by hazardous agents of various chemical or biological nature.
      The biomarkers make it possible to "monitor" the processes within the organism
      from the moment of toxic agent penetration to the development of clinical
      symptoms. Biomarkers offer the possibility of early detection of phenomena which
      tend to be arranged in the sequence of pathogenic changes, usually not detectable
      by the conventional methods. Depending on the type of processes which accompany
      the effect of a specified harmful environmental agent on the human organism it
      may be determined with the aid of the biomarkers, which are then classified as
      exposure, health effect, and individual susceptibility. By integrating such
      concepts as exposure, health effect, and individual susceptibility, enhanced
      analysis of the problem of health risk in people exposed to environmental toxic
      agents has become possible.

PMID- 7640906
TI  - The effect of the working environment on occupational skin disease development in
      workers processing rockwool.
AB  - Our examinations involved 259 workers (46 females and 213 males) manufacturing
      insulation matting of rockwool and phenol-formaldehyde resin. The control group
      included 529 people. All of the subjects were patch-tested. The age-adjusted
      relative risk was used as a measure for evaluating the increase in the incidence
      of dermatitis and allergy to metals. An atomic absorption method was used to
      determine metal content in rockwool. Dermatitis was found in every fourth subject
      examined, oil acne in every tenth subject; 7.3% of the subjects examined were
      found to be allergy-positive to nickel, 6.9% to chromium, 5.0% to cobalt, 3.1% to
      formaldehyde, 1.5% to phenol-formaldehyde resin, 0% to phenol. Out of the 39
      subjects examined twice (in 1988 and 1990), 5 were found to be allergy-positive
      to nickel during the second examination. A statistically significant increase in
      the risk of incidence of occupational dermatitis and allergy to nickel and cobalt
      was found in people producing insulation products made of rockwool. The latter
      material was found to contain 200 ppm chromium, 88 ppm nickel and 29 ppm cobalt.

PMID- 7640907
TI  - Cardiac arrhythmia in women performing heavy physical work.
AB  - The objective of this work was to determine the response of the circulatory
      system to heavy physical work (the average energy expenditure was about 5000
      kJ/shift). The tests were performed on a group of 35 women aged between 24 and 50
      years, employed at a printing office as printing machine operators. The average
      length of employment for the group was 17 years (3-28 years). A 24-hour Holter
      ECG recording was taken on these women with the aid of an Oxford Medilog 3000
      system. Before and after each recording, the arterial blood pressure was
      measured. Based on the ECG recordings, the heart rates during work, leisure time
      and sleep were calculated and the morphologies of the recordings were evaluated.
      In the group investigated, the abnormality in 24-hour ECG recordings classified
      as pathology, were found in 9 women within this group. Frequent ventricular
      premature beats (ExV) occurred in 3 women, ventricular bigeminy in 1 women, and
      single R/T excitations in 1 women. Frequent premature supraventricular
      extrasystols (ExSV) were found in 4 women, and within this number, in 1 woman
      both those heart rhythm disturbances were found. The heart rhythm disturbances
      occurred in connection with the performed physical task. Sinusal pauses were
      found in 2 women and A-V Mobitz II block was found in 1 women within the group
      investigated. Those changes occurred at night. No resting ECG changes were
      observed. The high frequency of occurrence of pathological changes in the group
      investigated indicates that the careful control of the state of the circulatory
      system in people performing heavy physical work is required.

PMID- 7640908
TI  - Effect of physical exercise on antioxidative enzymatic defense in blood platelets
      from healthy men.
AB  - Our investigations were carried out on blood platelets obtained from 41 healthy
      men subjected to submaximal physical exercise. Physical exercise was found to
      induce a significant increase of superoxide dismutase, catalase and glutathione
      peroxidase activities in blood platelets accompanied by a decrease of platelet
      malonyldialdehyde and thromboxane A2 concentration.

PMID- 7640909
TI  - Non-mutagenicity of thiadiazole-1,3,4 derivatives in Salmonella typhimurium
      strains.
AB  - The Ames mutagenicity assay with Salmonella typhimurium strains (TA97a, TA98,
      TA100 and TA102) was used to investigate the ability of five dyes (thiadiazole
      1,3,4 derivatives) to induce point mutations. The results did not reveal any
      mutagenic effects of the tested dyes on the S. typhimurium strains. No mutagenic
      activity was observed in the experimental series with and without exogenous
      activation.

PMID- 7640910
TI  - Lymphocytes, T and NK cells, in men occupationally exposed to mercury vapours.
AB  - Lymphocytes, T-cells (CD3+), T-helper (CD4+) and T-suppressor (CD8+) as well as
      NK-cells (CD16+) counts were determined in the peripheral blood of 81 males
      occupationally exposed to metallic mercury vapours and of 36 non-exposed males
      using monoclonal antibodies in indirect immunofluorescence tests. Mean weighted
      mercury concentration in air accounted for 0.0028 mg x m-3. Urine mercury
      concentrations ranged from 0 to 240 micrograms x 1(-1) and concentrations in the
      blood varied from 0 to 30 micrograms x 1(-1). Stimulation of T-lymphocytes
      manifested by an increased number of T-cells, T-helper and T-suppressor was
      observed. Quantitative change in T-cells night be an immunological index of
      exposure to mercury vapours as indicated by a positive correlation between the
      exposure duration and the number of these cells.

PMID- 7640911
TI  - Hazard prevention and control in the work environment. Report of a WHO meeting.
AB  - On the 19-21 September 1994 an international meeting of experts was convened at
      the World Health Organization office in Geneva. The result of this meeting was
      the formation of the PACE working group. PACE stands for 'Prevention And Control
      Exchange'. It is a programme designed to stimulate the sharing of solutions and
      control measures in order to reduce occupational hazards. Internationally there
      is wide agreement on the need for sharing of knowledge and a realisation that a
      collaborate effort is required.

PMID- 7640912
TI  - Cellular composition of cervical smears taken by general practitioners.
AB  - The quality of the cervical smears taken by general practitioners, and also by
      some practice assistants, of the Dutch Screening Programme in the region of
      Nijmegen was evaluated. Of 18,398 preventive cervical smears taken by GPs in this
      region, 437 (2%) were diagnosed as "class" 0 and 2907 (16%) smears did not
      contain endocervical cells (EC-). The quality of the smears per general
      practitioner varied enormously. The percentage of smears without endocervical
      cells taken by six practice assistants was 18. During the screening period the
      percentage of smears without endocervical cells taken by GPs decreased from 19
      (1989) to 14 (1992). In February 1990 the six practice assistants followed a
      theoretical and practical course on cervical smear-taking. Remarkable was the
      decrease in the percentage of smears without an endocervical component from 25%
      in 1990 to 13% in 1991. The quality of smears taken by GPs would improve if the
      general practitioner had more experience in smear-taking. We recommend to offer
      GPs the opportunity to take practical training courses in smear-taking, just as
      the practice assistants in this project.

PMID- 7640913
TI  - AUDILAB: quality audit simulation to prepare biomedical testing laboratories for
      accreditation.
AB  - In order to prepare biomedical laboratories for accreditation a quality audit
      simulator has been developed. By means of a dialogue with the laboratory, AUDILAB
      simulates the process by which the auditor identifies deviations or assesses
      conformity to the standard. AUDILAB is based on a knowledge processing system
      accessible via Minitel (French videotex terminal). With reference to the EN 45001
      standard which is the European standard concerning the "General criteria for the
      operation of testing laboratories", it provides an assessment of the laboratory's
      degree of conformity and prompts it to take corrective action.

PMID- 7640914
TI  - Clinical practice and the use of laboratory tests at the May 15 Hospital in
      Egypt.
AB  - The purpose of this study was to assess physicians' practices in the use of
      laboratory tests at a public hospital in Egypt. Methods included medical record
      reviews, interviews with selected physicians, literature review, and cost
      analysis. Three variables were examined in the medical record: appropriateness of
      laboratory tests, laboratory tests performed but not used as a basis for clinical
      treatment, and laboratory tests requested but not performed. Direct and indirect
      costs for each test were calculated. Results of the study indicated that 31.4% of
      the tests were inappropriate, 20.1% of test results were not used in treatment
      decisions, and 16.3% were not performed. Inappropriate and unused tests accounted
      for 22.6% of the annual total budget deficit for the hospital laboratory. To
      improve the quality of patient care and to decrease the wasteful use of
      resources, the hospital formed process improvement terms to develop clinical
      guidelines for problem-prone tests and to improve processes for requesting and
      providing laboratory results in a timely manner.

PMID- 7640915
TI  - When time is precious--time lags as indicators of quality of care in acute
      myocardial infarction.
AB  - Intravenous thrombolytic therapy is known to reduce mortality in acute myocardial
      infarction. The effect is highly time dependent and is uncertain 12 hours or more
      after onset of major symptoms. In order to assess aspects of quality of care for
      the initial treatment of acute myocardial infarction, pre- and in-hospital time
      lags were recorded in four Norwegian hospitals for patients admitted to the
      intensive care unit with acute myocardial infarction and for patients who
      received thrombolytic therapy for acute ischemic coronary heart disease. Four
      hundred and forty-six patients were included, of whom 45% (199) received
      thrombolytic medication, 159 after the initial assessment and 40 after
      observation and reassessment. All patients receiving thrombolytic therapy had a
      history of pain, and 94% (187) had significant ECG-changes. Median pre-hospital
      time was 240 (1. and 3. quartil 120, 519) min for the total sample and 155 (91,
      280) min for those who received thrombolytic medication after the primary
      assessment. Median in-hospital time before thrombolysis was 55 (35, 75) min for
      the latter group, and 177 (111, 335) for those who were observed and reassessed.
      We conclude that there is considerable potential for reducing the time lag for
      initiation of thrombolytic medication in acute myocardial infarction. Audits,
      written guidelines and standards are necessary to reduce in-hospital time.

PMID- 7640916
TI  - Internists' evaluation of guidelines: the IMCARE Practice Guidelines Network.
AB  - This paper presents the attitudes and experiences of one group of practicing
      internists, the IMCARE Practice Guidelines Network, with clinical practice
      guidelines. From its beginning the Network has enjoyed close ties to both the
      Agency for Health Care Policy and Research (AHCPR) and the Institute of Medicine
      (IOM) with their guideline mandates. The Network is a self-selected group of 471
      internists and their subspecialty colleagues, dispersed throughout the U.S.
      Network member evaluations of draft clinical practice guidelines present a
      compelling case for the need for clarity of language and a more condensed
      guideline structure. As Network members' critique indicates, once published,
      guidelines have become communication tools.

PMID- 7640917
TI  - Balancing science and practice in indicator development: the Maryland Hospital
      Association Quality Indicator (QI) project.
AB  - This paper describes the technical and conceptual aspects in the development of
      an indicator project to measure hospital performance. Almost a decade ago, a
      research based--hence explorative, series of inpatient and ambulatory care
      indicators were developed. This paper describes some of the most fundamental
      technical and applied knowledge gleaned from the study and applicable to all
      quality assurance/quality improvement activities. These findings, and the
      resulting indicator development guiding principles, are based on more than 900
      hospitals' experience in the US, Japan, and England. Although this paper presents
      the necessary scientific underpinning for a valid and reliable analysis, its
      principal emphasis is on the practical applicability of this decade old research
      project aimed at measuring select outputs of performance and identifying and
      explaining the determinants of these outputs.

PMID- 7640918
TI  - Impact of non-response and of late-response by patients in a multi-centre
      surgical outcome audit.
AB  - OBJECTIVE: To determine the impact of non-responders on the results of a multi
      centre surgical outcome audit, factors associated with failure to respond and to
      assess the benefits of pursuing non-responders beyond two reminders. DESIGN: A
      multi-centre prospective cohort study. SETTING: English health regions of Wessex,
      Mersey and Northern and South-West Thames. SUBJECTS: Five thousand two hundred
      and eighty-one (5281) consecutive cases undergoing surgery for prostate disease
      for a 6-month period. MAIN OUTCOME MEASURES: Socio-demographic and clinical
      factors associated with response (both early and late) and associations of these
      factors with outcomes (change in symptom severity, overall outcome, and
      occurrence of complications) three months after surgery. RESULTS: An overall
      response rate of 82.4% was achieved. Non-responders were likely to be older and
      in poorer physical health than responders. Although non-response would lead to
      the results of an audit overestimating the benefit and underestimating the
      adverse effects of surgery, the size of these errors is small. Pursuit of a
      random sample of non-responders beyond two reminders led to 45% responding,
      potentially boosting the overall response rate by 8% to a total of 90.4%.
      However, there were few significant differences between these late responders and
      those who responded earlier suggesting that effort and resources expended in
      obtaining their response would not be justified in the routine practice of audit.
      CONCLUSIONS: The results show that in a large multi-centre audit of post
      operative patient perceived outcome, a response rate in excess of 80% will
      provide sufficiently accurate data for assessing the overall outcome of the
      service.

PMID- 7640919
TI  - Quality assurance in an ear, nose and throat department in Saudi Arabia. A
      surgical audit.
AB  - Quality assurance (QA) in health care is being introduced in developing countries
      also. However, QA still meets resistance from some clinicians. A prospective
      voluntary surgical audit was set up in the ENT department of a university
      teaching hospital in Saudi Arabia. Roles, responsibilities and objectives were
      defined and designated facilities were provided. There were 2125 admissions and
      2389 operations in a 3-yr period. The stated objectives were achieved concerning
      resource management, post-graduate training, and, especially, the successful
      establishment of surgical audit as an on-going and open-forum activity in a
      developing country. We conclude that other clinicians can feel encouraged by our
      positive experience and implement QA.

PMID- 7640920
TI  - Localisation using physical devices, radioisotopes and radiographic methods. I.-
      Demonstration of tissue interfaces within the body by ultrasonic echo sounding.
      1961.

PMID- 7640921
TI  - Ultrasonic assessment of hemidiaphragmatic movement: an indirect method of
      evaluating mediastinal invasion in non-small cell lung cancer.
AB  - This preliminary study aimed to assess the potential value of diaphragmatic
      ultrasound (DUS) in evaluating phrenic nerve involvement indirectly, in the non
      invasive pre-operative staging of mediastinal invasion in non-small cell lung
      cancer (NSCLC). A prospective study of 30 patients with NSCLC comparing the
      findings of diaphragmatic ultrasound, chest radiograph, computed tomography (CT)
      thorax and mediastinoscopy was performed. In all cases adequate quantitiative
      assessment of hemidiaphragmatic excursion was obtained. There was discordance in
      four of 30 patients between DUS and chest radiograph. Three of nine patients with
      extensive mediastinal disease on CT had abnormal DUS, and two of eight patients
      with indeterminate mediastinal disease on CT had abnormal DUS and were later
      found to be non-resectable. No abnormal cases of DUS were found in those cases
      with normal mediastinal CT. There was no clear relationship between the site,
      size and side of the primary tumour on CT, or its pleural or diaphragmatic
      contiguity, and hemidiaphragmatic excursion. There was concordance between DUS
      and mediastinoscopy in 17 of 21 patients. Two patients had normal mediastinoscopy
      and abnormal DUS but were not resectable at thoracotomy. No patient with abnormal
      DUS was resectable. DUS may be of potential value in the pre-operative staging of
      NSCLC and is therefore worthy of further evaluation.

PMID- 7640922
TI  - Percutaneous varicocele embolization in the treatment of infertility.
AB  - Clinical and sub-clinical varicoceles are associated with infertility and
      abnormal sperm parameters. Percutaneous embolization is a minimally invasive,
      safe, outpatient method of treatment which is cost effective in comparison to
      surgery. This study is a retrospective review of embolization of the spermatic
      vein using stainless steel occluding spring coils, performed in 116 males from
      two infertility clinics. Follow-up results were complete in 87 patients of which
      79 (91%) were successful both technically and clinically and all had sperm
      analysis performed both before and within 2 years after embolization. There was a
      highly significant increase in motility (mean 35% before, mean 46% after, p <
      0.001). Sperm density showed a trend towards improvement, but only p < 0.10, and
      there was no significant change in semen volume or morphology. The partners of 29
      men (33%) became pregnant in a total of 241 years of follow-up.

PMID- 7640923
TI  - Magnetic resonance imaging in patients with penile carcinoma.
AB  - The aim of the study was to determine the role of pre-operative magnetic
      resonance imaging (MRI), with and without contrast enhancement, in patients with
      penile carcinoma. Nine patients with a penile cancer were studied. The staging of
      the tumours was performed by clinical examination, MRI and surgery, according to
      the TNM classification. Six patients had primary tumours, of clinical stage T1 (n
      = 1) and T2 (n = 5). Three other patients had been previously treated and
      presented with a local recurrence of clinical stage T2. Surface-coil MRI was
      performed at 0.5 T with T1 weighted sequences before and after gadolinium-DOTA,
      and T2 weighted sequences. MRI results were compared with the clinical and
      surgical findings. T1 weighted sequences did not clearly demonstrate the margins
      of the tumours. T2 weighted sequences were the more useful in five patients,
      whereas contrast enhanced T1 weighted sequences allowed better delineation of the
      lesions in only three patients. Therefore, an imaging protocol should include
      spin echo T2 weighted sequences. Clinical examination correctly staged six of
      nine tumours; MRI, seven of nine tumours and the combination of both
      examinations, eight of nine tumours. MRI provided good evaluation of tumoral
      invasion into the penile shaft.

PMID- 7640924
TI  - A randomized, double-blind, parallel group trial of iomeprol, iohexol and
      iopamidol in intravenous urography.
AB  - The aim of this study was to compare the safety, tolerance, and diagnostic
      efficacy of iomeprol 350 mg I ml-1, iohexol 350 mg I ml-1, and iopamidol 370 mg I
      ml-1 in 90 adult patients undergoing intravenous urography. Radiographs obtained
      5, 10 and 15 min after contrast injection were blindly graded for quality on a
      four point scale as: 0, non-diagnostic; 1, diagnostic but of limited quality; 2,
      diagnostic and of good quality; 3, fully diagnostic and of very good quality. The
      sum of these scores indicated the overall diagnostic quality (0-4, non
      diagnostic; 4-8, diagnostic; 9-12, good or excellent). Contrast tolerability was
      evaluated by discomfort (heat or pain) associated with injection of the test
      compounds, and patients were monitored and questioned for adverse experiences.
      The quality of the individual radiographs was assessed as diagnostic and good or
      fully diagnostic and very good in most cases, with no significant differences
      between the three study groups, and overall scores were predominantly good or
      excellent (p = 0.55). All adverse reactions were transient and non-serious, and
      most of them were reported as mild in intensity. There were no significant
      differences between the three groups for heat sensation (p = 0.29). Pain at the
      injection site was reported only in the iohexol group (p = 0.104). It is
      concluded that iomeprol 350 mg I ml-1 is at least as safe and effective as
      iohexol 350 mg I ml-1 or iopamidol 370 mg I ml-1 when used for intravenous
      urography.

PMID- 7640925
TI  - Ultrasound guided aspiration of symptomatic supraspinatus calcific deposits.
AB  - 11 consecutive patients with shoulder pain were referred from the shoulder clinic
      for plain radiography. Supraspinatus calcific deposits were suspected after other
      causes of shoulder pain had been eliminated by clinical examination and local
      anaesthetic tests. Radiographs confirmed calcific deposits in all 11 shoulders
      and all deposits were shown by ultrasound to be lying in the supraspinatus
      tendon. Using a free-hand ultrasound guidance technique, a 19 G needle was passed
      percutaneously into all 11 shoulders in an attempt to aspirate the deposit. Six
      patients experienced immediate pain relief or relief on the same day, whilst four
      others were pain free at the 2 weeks follow-up clinic. One patient who was though
      to have a co-existing supraspinatus tear diagnosed by the scan was
      symptomatically unchanged.

PMID- 7640926
TI  - The measurement of nuchal translucency with transabdominal and transvaginal
      sonography--success rates, repeatability and levels of agreement.
AB  - The objective of this prospective observational study was to assess the abilities
      of transabdominal sonography (TAS) and transvaginal sonography (TVS) to measure
      nuchal translucency (NT) and to establish the levels of agreement between the two
      scan mode measures. The study was carried out in the Fetal Medicine Unit and 242
      pregnant women were recruited from a routine dating scan clinic. All patients
      underwent TAS and TVS, and two separately obtained measurements of the NT were
      recorded. The ability to measure NT and the repeatability and levels of agreement
      between the scan mode measures was assessed. A measurement of NT was obtained in
      92% and 90% of fetuses using TAS and TVS, respectively, and in 100% of fetuses by
      combination of the scan modes. Failure to measure NT with TAS was due to
      inability to obtain mid-sagittal views because of unfavourable fetal lie or poor
      resolution, especially in patients with high body mass indexes. Although there
      was generally good correlation between the two scan mode measurements, a
      significant overmeasuring of NT was observed with TAS (mean difference +/- SD:
      0.10 +/- 0.29 mm, p < 0.01). The repeatability coefficients were 0.40 mm and 0.22
      mm for TAS and TVS, respectively. An examiner needs to have the ability and
      equipment to perform TAS and TVS to consistently measure NT. Considering the
      overmeasurement of NT with TAS and the improved repeatability with TVS,
      measurements of NT in a screening programme for chromosomal abnormalities should
      be by TVS, at least when a prior TAS reveals a value close to a threshold level.

PMID- 7640927
TI  - Multispiral three-dimensional computed tomography in the investigation of
      craniosynostosis: technique optimization.
AB  - 21 infants with craniosynostosis were studied with a new three-dimensional (3D)
      computed tomography (CT) methodology. We describe technique optimization using
      multiple spiral data acquisitions with low dose (85 mAs) technique. One caudal
      volume of 3 mm slice thickness was obtained with a further two volumes of 1 mm
      slice thickness at the vertex. Image reconstruction of spiral raw data allowed
      overlapping 3 mm sections to be generated without the dose increase that would
      result from conventional axial CT scanning. We illustrate common technical
      artefacts of 3D CT and explain their cause and solution. A dramatic dose
      reduction to the lens was achieved with no loss in 3D image quality. Lens dose
      was 8.91 mSv compared with 24.6 mSv using the standard paediatric head technique.

PMID- 7640928
TI  - Implementation of multiple isocentre treatment for dynamic radiosurgery.
AB  - Radiosurgery using the dynamic rotation technique with a single isocentre was
      introduced at the Toronto-Bayview Regional Cancer Centre (T-BRCC) in 1988. Since
      then, over 100 patients have been treated. It was soon recognized that 25-30% of
      patients were referred with either non-spherical lesions or multiple lesions
      located sufficiently close together that consideration had to be given to the
      overlapping dose distributions throughout the treated volume. To treat these more
      complex targets a multiple isocentre technique was developed which also took
      account of these effects and the resulting normalization problem. This technique
      was implemented in September 1992. Comparisons between calculated doses and
      actual doses delivered have been undertaken using a spherical phantom containing
      radiochromic film. Measured dose distributions agreed with the planned
      distributions to within +/- 1 mm. The effect of multiple isocentres on the
      penumbra of dose distributions has been examined. The methods adopted for the
      normalization of treatment plans and clinical examples illustrating the
      application of the multiple isocentre technique are presented.

PMID- 7640929
TI  - Are moving junctions in craniospinal irradiation for medulloblastoma really
      necessary?
AB  - The case notes of 35 patients treated for medulloblastoma using a standard
      technique of craniospinal irradiation (CSI) from 1978 to 1992 were reviewed. Two
      large opposed lateral fields to the whole brain and an orthogonal posterior
      spinal field were used. The position of the junction between the fields was
      constant throughout treatment with no feathering and no gap. We present our
      results, review the literature and discuss the need for feathering. The junction
      between the cranial and spinal fields produces an area of dose inhomogeneity but
      the clinical significance of this and the effect of feathering is uncertain.

PMID- 7640930
TI  - An estimate of the margin required when defining blocks around the prostate.
AB  - The portal films of 54 consecutive patients treated for primary prostate cancer
      have been compared to the simulation films. The systematic and random uncertainty
      in the set-up, defined by the couch movement required to move the patient to the
      simulated position, was determined to be 1.6 mm UP (SD 3.3 mm), 0.3 mm RT (SD 2.6
      mm) and 1.3 mm IN (SD 2.4 mm). The area of fields defined on simulation films was
      compared with that on portal films to determine the error in block production
      which was -0.7 mm (SD = 0.9 mm). Five sources of uncertainty in the radiotherapy
      have been identified, three occur before and two during the course of treatment.
      A method for combining these uncertainties is proposed and used on the data
      obtained in this study. This provides estimates of the margin required when
      drawing blocks so that the minimum dose to the target is 95% of the prescription
      in 95% of treatments. The block margins are not uniform and range from 21 mm,
      when drawing the block outline to the posterior on a lateral film, to 13 m when
      drawing laterally on an anterior film.

PMID- 7640932
TI  - Mammography in the follow-up after breast-conserving treatment in cancer of the
      breast: suitability for mammographic interpretation, validity and interobserver
      variation.
AB  - The aims of this study were to determine the suitability for radiographic
      interpretation, interobserver variability and validity of mammography after
      breast-conserving treatment. Initial and post-treatment mammograms of 100
      consecutive patients treated between 1982 and 1987, with a minimal follow-up of 5
      years, were independently selected for review by two radiologists. Mammograms
      were classified according to suitability for interpretation and radiological
      diagnosis based on the presence of characteristics of malignancy. The
      interobserver variability was expressed in kappa values, the validity in a
      receiver operating characteristic (ROC) plot. 534 post-treatment and 86 initial
      mammograms of 92 patients were obtained. Suitability for interpretation was not
      different from pre-treatment mammograms and was significantly associated with
      age, being better in the age group over 50 years. No association was observed
      between suitability for interpretation and treatment-related factors, even if
      irradiation was combined with concurrent chemotherapy. Reliability of conclusions
      regarding sensitivity and specificity in this study are limited due to the small
      number of events. Interobserver agreement concerning classification was moderate
      (weighted kappa = 0.49). ROC analysis showed an optimal decision threshold
      between the "uncertain" and "suspect" categories of malignancy, resulting in a
      sensitivity of 86% and a specificity of 98%. The appearance of new pathological
      microcalcifications with or without tumour mass seemed to be the most important
      characteristics of malignancy predicting local relapse. No clear alteration in
      suitability for interpretation was observed in the mammograms after breast
      conserving treatment, even if irradiation was combined with concurrent
      chemotherapy. Mammography after breast conserving-treatment may be slightly less
      sensitive but is equally specific compared with mammography in the screening
      situation.

PMID- 7640931
TI  - A comparison of bone densitometry measurements of the central skeleton in post
      menopausal women with and without vertebral fracture.
AB  - The purpose of this investigation was to compare the ability of two different
      bone densitometry techniques (quantitative computed tomography and dual X-ray
      absorptiometry) to discriminate subjects without any vertebral fracture from
      those with definite vertebral fractures. Bone mineral density (BMD) was
      determined in 112 post-menopausal women. 83 women were classified free of
      vertebral fracture and 29 were considered to have definite vertebral fractures.
      Quantitative computed tomography (QCT) was performed using three different spinal
      regions of interest. Dual X-ray absorptiometry (DXA) was measured at the spine
      (both in posteroanterior (PA) and lateral (L-DXA) projection, and at hip (total,
      neck and Ward regions). An additional estimated volumetric BMD was derived from
      the PA and L-DXA spine scans. Individuals with definite vertebral fractures had
      lower bone mineral density for each of the methods and regions of interest (ROI).
      Spinal QCT results, total and Ward hip DXA results showed the greatest percentage
      decrement. Odds ratio estimates revealed a significant relationship between BMD
      and fracture with spinal QCT, hip, and volumetric spinal DXA. The greatest areas
      under the receiver operating characteristic (ROC) curves were found with results
      of spinal QCT, total and Ward hip DXA, and volumetric spinal DXA measurements. It
      is concluded that spinal QCT and femoral total DXA measurement may be preferred
      to PA and lateral L3 DXA measurements.

PMID- 7640933
TI  - Technical note: dual compression mammography using computed radiography.
AB  - On mammography most malignant growths may be seen as a tethered mass or
      architectural distortion. Benign lesions such as cysts and fibroadenomas have no
      focal tethering and are usually well circumscribed. Computed radiography (CR) is
      a direct digital system which may be used for mammography. One of the main
      advantages of CR is its wide exposure latitude allowing images to be acquired at
      lower exposures than required for film-screen systems. A technique was developed,
      utilizing the exposure latitude of CR, to acquire two mammograms of the same
      breast at two slightly different compressions, but using approximately the same
      exposure as a single film-screen mammogram. These images were then "animated" on
      a computer allowing the fibrous septa movement to be visualized. The movement of
      the fibrous septa in the presence of an abnormality was used to help confirm
      whether a lesion was benign or malignant. This technique may have clinical
      application in classifying architectural distortions and masses which are
      ultrasonically benign but later found to be malignant. Microcalcifications cannot
      be used as a diagnostic indicator with this technique because of the increased
      noise associated with the lower exposures. The increased noise did not affect the
      visualization of masses.

PMID- 7640934
TI  - Case report: the role of arteriography in patients with isolated neurological
      deficit following a penetrating upper limb injury.
AB  - Two cases are described of patients who presented with isolated neurological
      deficit following penetrating injury to the upper limb. Arteriography
      demonstrated brachial artery false aneurysm formation in each case. There are
      accepted indications for emergency angiography following stab wounds including
      pulse deficit, vascular bruit, expanding haematoma and hypotension with no
      obvious cause. Indirect indicators of vascular damage include proximity of the
      injury to an artery with no physical signs or isolated neurological deficit.
      These indications do have a significant association with concurrent arterial
      injury and should be investigated by elective angiography if the patient is
      haemodynamically stable.

PMID- 7640935
TI  - Case report: brain metastases from papillary carcinoma thyroid.
AB  - Papillary carcinoma, the commonest thyroid malignancy, has a good prognosis and
      low incidence of distant metastases. Brain metastasis is extremely rare with a
      frequency of 0.1-5% in reported series. The clinical details of two cases of
      histologically proven brain metastases from papillary thyroid cancer treated in
      our centre are presented. In one patient, the lesion was in the cerebellar
      hemisphere, and in the other, the frontal lobe. Also presented is a review of the
      literature of this unusual clinical presentation.

PMID- 7640936
TI  - Case report: multiple thoracic haemangiomas--a rare cause of spinal cord
      compression.
AB  - Benign haemangiomas are a rare cause of mediastinal masses. We present a patient
      with multiple thoracic wall and mediastinal haemangiomas who developed spinal
      cord compression as a result of extradural extension of the haemangiomas. This is
      a rare cause of spinal cord compression.

PMID- 7640937
TI  - Case of the month: an unusual cause of baldness.

PMID- 7640938
TI  - A simple method for skin/lesion localization using magnetic resonance imaging.

PMID- 7640939
TI  - Systematic errors in displacement measurements performed using CT scannograms.

PMID- 7640940
TI  - Proceedings of the British Medical Ultrasound Society 26th annual meeting.
      Scarborough, 14-16 December 1994. Abstracts.

PMID- 7640941
TI  - [Sanaven: topical venous medication with comprehensive effect].

PMID- 7640942
TI  - Pathophysiology and current concepts in the diagnosis of obstructive jaundice.
AB  - Although diagnosing jaundice is quite simple, elucidating the underlying cause
      can be challenging. Of particular importance is early identification of patients
      whose jaundice is secondary to extrahepatic obstruction, or what is erroneously
      referred to as surgical jaundice. Unfortunately, the clinical and biochemical
      presentation of biliary obstruction is often nonspecific and indistinguishable
      from other hepatocellular disorders. Over the past decade, there have been
      numerous technological advances that have radically changed the diagnostic
      approach to jaundice. Modern gastroenterologists currently have a large
      armamentarium of imaging and diagnostic procedures from which to choose. We
      present a review of the pathophysiology, differential diagnosis, and diagnostic
      evaluation of obstructive jaundice. Special emphasis is placed on reviewing
      laboratory tests and imaging studies. We provide a simple and rational algorithm
      for judicious use of new technology in the work-up of obstructive jaundice.

PMID- 7640943
TI  - Hepatotoxicity: newer aspects of pathogenesis and treatment.
AB  - The etiology and the pathogenesis of different forms of hepatotoxicity are
      discussed; case reports are included to illustrate the importance of history
      taking and examination of liver tissue in establishing a specific diagnosis. The
      role of alcohol as a hepatotoxin as well as an enzyme-inducing agent is stressed.
      Genetic factors have been identified that may determine susceptibility to
      alcoholism and the hepatotoxic effects of alcohol and other compounds. Some cases
      of drug-induced cholestasis may be explained by disturbances in the known
      pathways of bile acid uptake, transport, and excretion. The importance of small
      duct destruction in patients with progressive drug-induced cholestasis is
      discussed. Finally, the potential hepatic complications of some nonprescription
      remedies used by adherents of "alternative medicine" are described, emphasizing
      the relevance of thorough etiological inquiry in all patients presenting with
      hepatic dysfunction.

PMID- 7640944
TI  - Access routes for enteral nutrition.
AB  - Comprehensive management of patients includes a thorough evaluation of
      nutritional requirements. The risks and the benefits of enteral and parenteral
      supplementations have been heavily investigated. Recent literature supports use
      of the gastrointestinal tract, when functioning, as the preferred route for
      supplemental nutrition. There are multiple access routes available to clinicians
      to provide enteral nutrition, including feeding tubes, which can be placed
      transnasally, percutaneously, or surgically. These various techniques have
      individual indications, contraindications, and complications associated with the
      procedures. They also have varying levels of invasiveness and overall durability.
      We discuss the different access routes available for enteral feeding, as well as
      the process for selecting the most appropriate route.

PMID- 7640945
TI  - Immunosuppressive therapy of inflammatory bowel disease: a historical
      perspective.
AB  - I present the progressive development of treatment with immunosuppressive drugs
      for Crohn's disease and ulcerative colitis, starting with rationale, failure of
      corticosteroids for maintenance, early observations, controlled trials,
      collaborations, toxicity (including fear of neoplasms), and considerations in
      pregnancy. Emphasis is on 6-mercaptopurine and azathioprine. Observations on
      methotrexate and cyclosporine are included, as well as advice on when to initiate
      immunosuppressive therapy, what is occurring currently, and what is expected to
      occur in the near future.

PMID- 7640947
TI  - Cyclosporine: indications and use in gastrointestinal diseases.
AB  - Cyclosporine is the most important drug used in transplant medicine, and it has
      revolutionized the field of organ transplantation. It suppresses cytotoxic T-cell
      activity without producing myelosuppression. Recently, its use has been expanded
      to include an increasing number of immunologically mediated disorders. Many of
      these diseases involve the liver and the gastrointestinal tract, which is
      therefore of interest to practicing gastroenterologists. However, cyclosporine is
      associated with a number of adverse effects. A knowledge of these side effects
      and their management is essential for any physician who intends to use this drug.
      Current gastrointestinal indications and a practical approach to cyclosporine use
      in gastroenterology are discussed.

PMID- 7640948
TI  - Laparoscopic Nissen fundoplication.
AB  - Most patients with gastroesophageal reflux disease (GERD) can be treated
      effectively with medical therapy; however, in patients with severe GERD who are
      unresponsive to medical therapy, the lower esophageal sphincter (LES) is often
      found to be mechanically incompetent. Surgical therapy, which improves the LES
      antireflux barrier, may then be a good option. A very effective and popular
      antireflux procedure is the Nissen fundoplication, which can be safely done via
      the laparoscopic route. Preoperative evaluation should include contrast
      radiography, esophagoduodenoscopy (EGD) with biopsies, esophageal manometry, and
      24-hour pH monitoring. Indications for surgery include failure or inability to
      continue on medical therapy, GERD-related respiratory symptoms, and severe
      complications of GERD, such as ulceration, stricture, and Barrett's esophagus. A
      short, loose Nissen fundoplication is ideal for patients with normal esophageal
      body motility. Operative complications are infrequent, and they include gastric
      perforation, bleeding, and pneumothorax. Following the laparoscopic approach,
      nearly all patients can leave the hospital on the first or second postoperative
      day. Follow-up esophageal manometry and 24-hour pH monitoring show the same good
      long-term results as seen after open Nissen fundoplication. Laparoscopic Nissen
      fundoplication can be performed safely and effectively with all of the advantages
      of a minimally invasive approach.

PMID- 7640946
TI  - Diagnosis and therapy of hereditary polyposis syndromes.
AB  - The hereditary polyposis syndromes include the adenomatous polyposis syndromes
      (familial adenomatous polyposis and Gardner syndrome, and Turcot syndrome) and
      the hamartomatous polyposis syndromes (Peutz-Jeghers syndrome, juvenile
      polyposis, and Cowden's disease). The adenomatous polyposis syndromes are
      characterized by numerous adenomatous polyps throughout the entire colon and a
      spectrum of extracolonic manifestations; they invariably progress to colorectal
      cancer without appropriate intervention. The hamartomatous polyposis syndromes
      are characterized by diffuse intestinal or colonic hamartomatous polyps, such as
      juvenile polyps. Although hamartomatous polyps have virtually no malignant
      potential, the hamartomatous polyposis syndromes are associated with increased
      risk of cancer, both within and outside the small intestine and the colon.
      Diagnosis of symptomatic polyposis is by colonoscopy, but in presymptomatic
      screening of familial adenomatous polyposis, genetic testing can be effective,
      and it is becoming increasingly available though research laboratories.
      Management involves treatment of affected individuals, counseling of patients and
      their families, screening of at-risk individuals, and surveillance of affected
      patients for extracolonic cancers. Treatment of adenomatous polyposis is
      primarily colectomy during the second or third decade. For the hamartomatous
      polyposis syndromes, surveillance for early cancers and their excision remain the
      only practical, although not totally satisfactory, approaches.

PMID- 7640949
TI  - Detection of EBV mRNA in nodular sclerosis type of Hodgkin's disease using in
      situ hybridization with EBER 1 and EBER 2 probes with regard to the
      immunophenotype of Reed-Sternberg cells.
AB  - Hodgkin's disease (HD) is a heterogenous disorder in terms of morphology,
      immunophenotype, genotype and association with viruses. Seroepidemiologic,
      immunohistochemical and molecular studies suggest that Epstein-Barr Virus (EBV)
      plays an important role in the pathogenesis of HD. We used in situ hybridization
      (ISH) with digoxigenin-labeled EBER 1 and EBER2 probes to examine a series of 28
      lymph node specimens from untreated patients from Poland with the nodular
      sclerosis NS 1 and NS 2 subtypes of HD to detect EBV mRNA in Reed-Sternberg cells
      (RSC), or in small non-neoplastic lymphocytes called "bystander cell" (ByC). EBV
      mRNA was detected in 12 of 28 cases (32.1%). Furthermore, the expression of
      Latent Membrane Protein (LMP) of EBV strongly correlated with expression of EBER
      1 and EBER 2 in RSC but not in "bystander cells", which were LMP negative. The
      correlation between EBV status and immunophenotype of RSC are discussed.

PMID- 7640950
TI  - The expression of multidrug resistance (MDR) molecule in acute leukemia and
      lymphoma.
AB  - Multidrug resistance (MDR) is associated with expression of P-glycoprotein in the
      malignant cells as the one of known mechanisms for this phenomenon. The isolated
      blast cells of 60 patients with acute leukemia and non-Hodgkin's lymphoma (NHL)
      were assayed for the expression of P-glycoprotein (P-170) with MRK16 antibody.
      The frequency of P-170 expression was studied in the different subtypes of
      leukemia and NHL based on blasts phenotype. In acute leukemia and lymphoma with B
      cell lineage of blast cells the percentage of P-170 positive samples was 41.3%,
      in the non-lymphoblastic leukemia--35.3% and the T cell lineage--75% of P-170
      positive samples. The expression of P-170 molecule was associated with: 1. T cell
      origin of blasts, 2. lymphoma form of proliferation. The P-170 assay selects the
      group of patients with higher risk of drug resistance for modified therapy.

PMID- 7640951
TI  - Cellular blue nevi with myxoid change--diagnostic difficulties and the review of
      the literature.
AB  - We report three cases of a rare morphologic variant of the cellular blue nevus,
      which usually occurs in young patients on the buttocks and lumbar area. This
      variant is characterized by the myxoid degeneration of the stroma, which
      separates alveolar nests of nevus cells. The uncommon occurrence and atypical
      pathologic features may bring about diagnostic pitfalls and unnecessary excessive
      treatment modalities, therefore, we tried to re-evaluate the criteria of
      diagnosis of cellular and malignant blue nevi.

PMID- 7640952
TI  - Oxygen--friend or foe?

PMID- 7640953
TI  - Infectious agents and joint diseases.

PMID- 7640954
TI  - Equine pleuropneumonia.
AB  - Pleuropneumonia is a clinically important equine disease, predisposed by a number
      of identifiable factors. Successful management is largely dependent on early
      identification and prompt initiation of appropriate treatment strategies. Rapid
      resolution of the disease process is associated with appropriate treatment
      commenced within 48 h of the causative insult. Lower airway contamination by
      oropharyngeal organisms and subsequent extension into the pulmonary parenchyma
      results in respiratory dysfunction and systemic toxaemia. Acute disease is
      associated with the isolation of facultatively anaerobic organisms, especially
      beta-haemolytic Streptococcus spp. and Pasteurellaceae. Delayed or inappropriate
      treatment is likely to result in chronic disease characterized by the involvement
      of anaerobic bacteria and a poor response to therapy. The primary mode of
      treatment for anaerobic infection of the human thorax is surgical drainage and
      resection of necrotic tissue but whilst such techniques have been described for
      the management of equine pleuropneumonia, the size of the equine thoracic cavity
      hinders accurate diagnostic evaluation and successful completion of such
      intervention. The chronic nature and cost of ongoing treatment and limitations on
      choice of antimicrobial agents warrant a poor prognosis for survival and a poorer
      prognosis for return to athletic endeavour.

PMID- 7640955
TI  - Early reproductive loss due to bovine pestivirus infection.
AB  - Bovine pestivirus infection has been mainly recognized as the cause of mucosal
      disease, a syndrome which occurs sporadically in weaned and adult cattle as a
      late sequel to foetal infection during the first 3-4 months of gestation.
      Infection has also been associated with the occurrence of congenital
      malformations, especially of the central nervous system. Following the
      development of improved diagnostic and research techniques, pestivirus has now
      been shown to be associated with significant early reproductive loss including
      fertilization failure, embryonic mortality and abortion. The principal
      determinant of the outcome of in utero infection in the bovine is the age of the
      conceptus when infection occurs.

PMID- 7640956
TI  - Antibodies to heat shock proteins in dogs with rheumatoid arthritis and systemic
      lupus erythematosus.
AB  - Antibodies to heat shock proteins of the 65 kDa group were demonstrated in canine
      sera and synovial fluid. This paper reports these antibody measurements in three
      groups of dogs with joint disease and compares them with those of a control
      population. Dogs with rheumatoid arthritis (RA) showed higher anti-heat shock
      proteins (HSP) antibody levels, in both their sera and synovial fluids, compared
      to the control dogs and these antibodies were predominantly of the IgG and IgM
      class; there was a significant correlation between IgM anti-HSP65 and IgM
      rheumatoid factors. There was also a significant correlation between anti-HSP65
      and antibodies to canine distemper virus, but only of the IgM class and the
      relevance of these antibodies to the overall pathogenesis of canine RA and, in
      particular, to the presence of canine distemper virus within the joint, are
      discussed.

PMID- 7640957
TI  - Ischaemia-reperfusion injury--a small animal perspective.
AB  - Disease processes that produce ischaemia are a common cause of morbidity and
      mortality in companion animals. The majority of damage to transiently ischaemia
      tissues occurs following reperfusion and not during ischaemia per se. This
      discovery raises the encouraging prospect that therapeutic intervention prior to
      reperfusion may reduce the severity of ischaemic damage. Recently, the central
      role of oxygen-derived free radicals (oxyradicals) in reperfusion injury has been
      demonstrated. It appears that the adverse consequences of ischaemic diseases can
      be reduced by optimizing the anti-oxidant capability of tissues with anti-oxidant
      nutrients or drugs. The importance of oxyradicals in individual ischaemic
      diseases of the dog and cat, however, remains largely uninvestigated. Similarly,
      the best pharmaceutical and nutritional approaches to the therapy of oxyradical
      mediated damage have yet to be devised.

PMID- 7640958
TI  - Distribution of lactate in plasma and erythrocytes during and after exercise in
      horses.
AB  - The distribution of lactate between red blood cells (RBC) and plasma was examined
      at rest, during exercise and 30 min after exercise in six Standardbred horses.
      Lactate and water concentrations were measured in blood and plasma samples
      collected prior to exercise, during the last 15 s of each step of an incremental
      exercise test and at 5 min intervals during the first 30 min after exercise. The
      mean ratio of RBC lactate concentration (RBCLa) to plasma lactate concentration
      (PLa) prior to exercise was 1.02 +/- 0.34. Haemoconcentration during exercise was
      associated with more rapid accumulation of lactate in plasma than in RBCs. Mean
      whole blood lactate concentration (BLa) was only 59% of PLa in samples collected
      during exercise. BLa was highly correlated with PLa during exercise (r = 0.98; P
      < 0.001), but individual PLa values differed from predicted BLa values by up to
      2.1 mmol l-1 when PLa exceeded 8 mmol l-1. At each exercise speed and time after
      exercise there was a large variation between horses in the ratio of BLa/PLa.
      During exercise at 11 m s-1 the ratio ranged from 0.46-0.73. The BLa/PLa ratio
      was significantly correlated with increasing exercise intensity, (r = -0.68, P <
      0.001) and with haematocrit, (r = -0.69, P < 0.001). The effects of PLa and
      haematocrit on the BLa/PLa ratio during exercise and the post-exercise period
      varied greatly between horses. The ratio of lactate concentrations in water of
      RBCs and plasma varied greatly during and after exercise (0.61-1.22). The ratio
      also varied considerably between horses, with coefficients of variation ranging
      from 14-34%. Lactate concentrations in RBC and plasma water vary greatly between
      horses during and after exercise. We concluded that lactate is unevenly
      distributed between red blood cells and plasma in blood samples centrifuged
      immediately after collection, and the variability depends on haematocrit.

PMID- 7640959
TI  - Pathological findings in the intestinal tract and liver of chicks after exposure
      to Salmonella serotypes Typhimurium or Kedougou.
AB  - Day-old chicks were inoculated either via the feed or by direct oral inoculation
      with salmonellas which were either invasive or non-invasive (serotypes
      Typhimurium and Kedougou, respectively). Colonization of the alimentary tract and
      visceral organs, determined by microbiological examination, occurred more quickly
      in birds inoculated orally with S. serotype Typhimurium compared with feed
      challenged birds. By contrast, S. serotype Kedougou remained confined to the
      alimentary tract. In birds inoculated either orally or via the feed, S. serotype
      Typhimurium, but not serotype Kedougou, was identified in the lamina propria of
      the caecum by immunostaining. Electron microscopic examination confirmed that the
      organisms were within macrophages.

PMID- 7640960
TI  - Sequence of an exon of tumour suppressor p53 gene--a comparative study in
      domestic animals: mutation in a feline solid mammary carcinoma.
AB  - Partial sequence determinations were performed on exon 8 of tumour suppressor
      gene p53 of cattle, sheep, goat, horse and pig. High sequence homology between
      these species and other species including dog, cat, chicken and man is
      demonstrated. A mutation CGG-->TGG (arginine-->tryptophan) was detected in a
      feline solid carcinoma of the mammary gland.

PMID- 7640961
TI  - Effect of testosterone on the pharmacokinetics of sulphadimidine and
      sulphachloropyrazine in roosters--a preliminary report.

PMID- 7640962
TI  - Attentional effects in dichotic listening.
AB  - This study addresses attentional effects in dichotic listening (DL) to consonant
      vowel syllables. Previous research has shown that ear advantages in DL are
      modulated by biased attention to either the left or the right ear. Attentional
      effects in DL can be the result of two processes: facilitation of reports from
      the attended ear, or suppression of intrusions from the nonattended ear. Sixty
      two students were tested with DL under three different task instructions:
      nonforced (divided) attention, attention forced to the right ear, and attention
      forced to the left ear. The main finding was inhibition of intrusions from the
      nonattended ear, combined with the facilitation of the correct reports from the
      attended ear during the two forced-attention conditions, compared with the
      nonforced condition. The results are discussed in relation to right hemisphere
      processing of dichotic input, and that attention may activate subcortically
      biased asymmetries which suppress input from the nonattended channel.

PMID- 7640963
TI  - Inspecting asymmetric presentations of words differing in informational and
      morphemic structure.
AB  - Are laterality effects in visual word recognition a product of functional
      asymmetry of the cerebral hemispheres or a result of stimulus inspection factors
      such as asymmetric eye fixations before and during visual presentation, different
      movement time to asymmetric targets, an interaction of the informative
      components, or morphemic structure of a target with a drop in acuity with
      distance? Two experiments were conducted to address these questions. Experiment
      One recorded the inspection of prefixed and matched control words presented
      unilaterally for 200 msec. Experiment Two displayed suffixed words and their
      appropriate controls. The words also varied in their information distribution.
      Reader's eye movements were monitored while they inspected the target words in
      preparation for a synonym judgement task. Measures of the location of the initial
      fixation on the screen showed that subjects were not biased to the right visual
      field prior to stimulus onset. When only those occasions in which the subject had
      correctly fixated the central cursor were analyzed, a robust right visual field
      advantage was observed on many of the target inspection time measures, but no
      reliable difference was observed for faster movement time to the right visual
      field's target compared to that observed in the left visual field. Neither the
      distribution of information within the word nor its morphemic structure affected
      the pattern of any inspection time measures. Consequently, such factors can be
      ruled out as threats to the hypothesis concerned with the functional asymmetry of
      the cerebral hemispheres.

PMID- 7640964
TI  - Favor referential representations.
AB  - Avrutin and Hickok (1993) argue that agrammatic patients have the ability to
      represent nonreferential or "government" chains ("who ... e") but not referential
      or "binding" chains ("which girl ... e"). By contrast, we propose the
      "referential representation hypothesis," which suggests that agrammatics attempt
      to cope with their well-known capacity limitations by favoring referential or
      content-based representations. This predicts that agrammatic patients'
      performance should degrade noticeably as task demands increase, and referential
      demands should take priority over computational ones. In a semantic task,
      referential phrases should lead to better or more accurate performances. In
      syntactic tasks, the availability of a referential or content-based
      representation will interfere with the development of a syntactic representation,
      resulting in worse syntactic performance on the referential phrases than on
      nonreferential ones. This predicts that agrammatic patients should incorrectly
      accept (resumptive) pronoun sentences with a referential wh-phrase because the
      pronouns will find the semantic or discourse referent of the referential wh
      phrase and take it as an antecedent for the pronoun. However, they should reject
      a (resumptive) pronoun in a sentence with the nonreferential question constituent
      "who" or "what." "Who" and "what" will remain in syntactic form, since they have
      only grammatical content and therefore will have only a "nonreferential"
      syntactic representation. Consequently, they cannot serve as the antecedent of
      the pronoun. These predictions were largely confirmed by the results of a
      grammaticality judgement study. Agrammatics performed well on questions with
      pragmatic biases but failed to distinguish reliably between grammatical and
      ungrammatical questions where pragmatic biases were neutralized. They assigned
      especially low ratings to object gap sentences with referential wh-constituents,
      as predicted. They assigned relatively high ratings to ungrammatical subject
      pronoun sentences with either type of wh- constituent. The agrammatics accepted
      ungrammatical reflexive sentences even though syntactic number and gender
      features alone could have been used to correctly judge the sentences. We
      attribute this, too, to the unavailability of a reliable syntactic representation
      of those phrases with referential or extragrammatical semantic content.

PMID- 7640965
TI  - Spelling and attention in early Alzheimer's disease: evidence for impairment of
      the graphemic buffer.
AB  - The present study was conducted to investigate the spelling ability of persons
      affected by mild Alzheimer's disease (AD). AD subjects produced more phonemically
      implausible (PI) spelling errors (e.g. enough-->enougigh) than normal subjects;
      in addition, AD subjects produced a higher percentage of PI spelling errors than
      normal AD subjects. We found that two clinical visual attention tests were better
      predictors of the number of PI spelling errors than a language measure. Moreover,
      we also found that AD subjects performed more poorly when they copied words that
      were viewed and removed from sight than when the same words were copied directly.
      In contrast, there was no significant difference in the performance of the normal
      elderly on direct and delayed copying tasks. AD subjects produced more errors
      when spelling long words than when spelling short words. Although the spelling
      performance of the normal elderly was also affected by the length of the words
      spelled, AD subjects showed a significantly greater drop in performance than
      normal subjects when the length of the words increased. The vocabulary of the
      short and long word lists did not differ in frequency of occurrence or
      imagability (i.e. abstractness). The results suggest that visual attention
      impairment and not language impairment accounts for the PI spelling errors of
      mild AD subjects. The results are discussed with reference to graphemic buffer
      deficits identified in case studies of stroke patients with dysgraphia.

PMID- 7640966
TI  - A property level analysis of lexical semantic representation in Alzheimer's
      disease.
AB  - In order to assess the hypotheses that Alzheimer's disease (AD) results in a
      property level restructuring, loss, or degradation of lexical-semantic knowledge,
      Alzheimer's patients and normal elderly subjects were presented with a property
      verification task in which they were asked to judge the truth value of
      telegraphic statements which paired objects with their properties (e.g., "Apple
      is red."). Objects with either high- or low-typical exemplars of categories
      (e.g., "oak" is a high typical exemplar of the category "tree." while "palm" is a
      less typical item). Properties were varied with respect to normatively determined
      dominance (e.g, "fins" is a high dominant property of "trout," while "slimy" is a
      less dominant property) and whether they were distinctive (i.e., served to
      distinguish between subsets of exemplars within a category) or shared among most
      or all category members (e.g., "stem" for the category "fruit"). Analyses of
      accuracy and reaction time data suggested that AD results in neither a loss per
      se of representation of properties, nor a reorganization of relations between
      objects' properties. However, results were consistent with a property level
      degradation of AD patients' object concepts. While there was no evidence for a
      differential degradation of distinctive vs shared properties, results suggested
      that AD patients have degraded representations of lower dominant properties and
      properties of low-typical category exemplars.

PMID- 7640967
TI  - Aphasia following right hemisphere lesion in a woman with left hemisphere injury
      in childhood.
AB  - The case of a 56-year-old woman who became aphasic following a right
      temporoparietal lesion is reported. At the age of 2, this woman had an acute
      infantile hemiplegia on the right side of the body and it was reported by
      relatives that a deterioration of language was also noted. There was a slow
      recovery of these deficits and she was considered as having normal language only
      at age 7. Although it is difficult to be sure about the hand preference of the
      patient before the stroke at age 2, the relatives were quite positive saying,
      that she previously preferred the right hand and that she became left handed. The
      CT scan showed an old left frontal ischemic lesion and a recent right
      temporoparietal lesion. This case illustrates the ability of the right hemisphere
      to take over functions of the left when a left lesion occurs in early stages of
      language acquisition. Although this is an accepted model for recovery, this is
      the only case in the literature with a documented early focal lesion of the left
      hemisphere. Other evidence comes from studies performed in populations where
      severe epilepsy may contribute to particular functional organization.

PMID- 7640968
TI  - Anatomical specialization of the anterior motor speech area: hemispheric
      differences in magnopyramidal neurons.
AB  - The lateralization of motor speech function to the left hemisphere is supported
      by multiple lines of evidence, but relatively little is known about the
      anatomical basis of that specialization. In a preliminary study, we recently
      reported that area 45 of the left hemisphere (Broca's area) contained a
      subpopulation of magnopyramidal neurons which were significantly larger than any
      seen in the homotopic region of the right hemisphere (Hayes & Lewis, 1993a). In
      the present study we examined a larger sample of cases in order to determine how
      consistently this difference is present in the population, if it is specific to
      Broca's area or is a general feature of cortical regions mediating lateralized
      functions, and whether the subpopulation of large magnopyramidal neurons in left
      area 45 can be distinguished by their chemical phenotype. In Nissl-stained
      sections from 19 human brains, the mean (+/- SD) cross-sectional area of the
      largest layer III pyramidal neurons in area 45 was significantly (p < .0001)
      greater in the left hemisphere (522.1 +/- 128.3 microns2) than in the right
      (454.1 +/- 121.5 microns2). This interhemispheric difference appeared to be a
      unique characteristic of the largest neurons, since the mean size of all layer
      III pyramids in this area was not significantly different in the left (206.2 +/-
      93.5 microns2) and right (213.3 +/- 103.9 microns2) hemispheres. In contrast to
      area 45, there was no interhemispheric difference in the mean cross-sectional
      area of the largest layer III pyramids in another lateralized region, primary
      motor cortex. In addition, in area 46, a region of prefrontal association cortex
      not known to be functionally lateralized, the mean somal size of the largest
      layer III pyramidal neurons was significantly (p < .001) smaller in the left
      hemisphere (402.4 +/- 84.9 microns2) than in the right (437.8 +/- 88.3 microns2).
      Finally, although the large layer III pyramids in area 45 were immunoreactive for
      nonphosphorylated neurofilament protein in both hemispheres, the mean cross
      sectional area of the largest labeled neurons was significantly larger (p < .002)
      in the left hemisphere (525.2 +/- 149.0 microns2) than in the right (490.3 +/-
      154.1 microns2). These findings demonstrate that layer III of Broca's area
      contains a distinctive subpopulation of neurons that may play an important role
      in the specific functional architecture of this region.

PMID- 7640969
TI  - Inter-rater reliability of a clinical test of standing function.
AB  - The Functional Standing Test (FST) has been proposed and described as an
      evaluative tool to assess a person's ability to perform one-handed reaching tasks
      while standing. The test items, several of which are identical to those in the
      Jebson Test of Hand Function, require the manipulation of objects on a counter
      top and on simulated kitchen shelves while the person is standing. The purpose of
      this study was to assess the inter-rater reliability of FST when it is
      administered to adolescents with spinal cord injuries who stand with braces, and
      to able-bodied young adults. Two testers administered the FST separately to three
      individuals with spinal cord injuries (SCI) below T-2 who stood with knee-ankle
      foot orthoses (KAFOs) and to 10 able-bodied people who stood unassisted. The
      order in which the testers operated was randomized and the Intraclass Correlation
      Coefficient (ICC (2,1)) was used to analyze inter-rater reliability. Eighty
      percent of the subtests were found to be moderately to very reliable when applied
      to either group on the same day. Half of the test items were categorized as
      having the same level of inter-rater reliability between the two sample
      populations. A modified version of the test eliminating unreliable components
      could serve as a valuable and inexpensive means of evaluating the effectiveness
      of various therapies and technologies to provide or assist standing function.
      Validity and specificity of the test remain the focus of future research.

PMID- 7640970
TI  - Ossification of the posterior longitudinal ligament of the spine: a case report.
AB  - Ossification of the posterior longitudinal ligament of the spine (OPLL) is a
      common cause of severe myelopathy and radiculopathy in Oriental populations. It
      typically involves the cervical spine. We present a 60-year-old Asian male with
      OPLL who developed progressively worsening cervical myopathy. The diagnosis and
      management are discussed.

PMID- 7640971
TI  - Evaluation of a thin-film peripheral nerve cuff electrode.
AB  - This is a study of the reaction of large nerves to implantation using a flexible,
      thin-film cuff electrode. Cuff electrodes were implanted on the sciatic nerve of
      three cats. An implantation period of six weeks allowed sufficient time for any
      injury responses in the nerve and connective tissue sheath around the cuff to
      develop. The electrode came off the nerve in one of the cats. In the remaining
      two cats, gross observation following explantation of the electrodes revealed
      encapsulation of the cuffs without swelling of nerve tissue. Histological
      evaluation did not demonstrate nerve injury. The nerve cuff electrodes, which are
      comprised of titanium and iridium coatings on a fluorocarbon polymer substrate,
      appeared unaffected by the implantation, and connective tissue encapsulation did
      not adhere to either the polymer substrate or metallization. Evaluation of the
      electrodes using activated iridium oxide charge injection sites in more extended
      studies is now being undertaken.

PMID- 7640972
TI  - Surgery in the acute treatment of spinal cord injury: a review of the past forty
      years.
AB  - This review is concerned with changes that have occurred during the past forty
      years in surgery as acute therapy for spinal cord injury. Included is a summary
      of experimental and clinical information upon which many of the decisions for
      change were based. Despite the evidence, following World War II, of improvement
      of mortality and morbidity with non-invasive treatment of spinal cord injuries,
      increased utilization of surgery has continued to the present. Reasons include a
      decrease in mortality and morbidity with modern surgical techniques, easier
      handling of the patient with an unstable spine who has early fusion, and the
      decrease in hospital and rehabilitation costs with earlier stabilization and
      earlier mobilization.

PMID- 7640973
TI  - Scoring acute spinal cord injury: a study of the utility and limitations of five
      different grading systems.
AB  - We recorded Frankel Scale, Yale Scale, Motor Index Score, Modified Barthel Index,
      Functional Independence Measurement scores, and important clinical parameters
      simultaneously and repetitively for 35 consecutive acute spinal cord injury
      patients. We found that 1) these scores can be determined as long as "yes/no"
      communication can be obtained reliably, pharmacological paralysis is not present,
      and a reliable observer with a flexible schedule is available, 2) impairment
      based scores (FS, YS, MIS) have little tendency to change during acute care, 3)
      function based scales (MBI, FIM) can be distorted by acute care phenomena which
      limit self care, 4) impairment-based and disability-based scales do not convert
      reliably, 5) none of these scales correlated strongly with common milestones for
      mobility or nutrition and 6) a good description of a population of ASCI patients
      can be made by a combination of two scales, one based on impairment and the other
      on disability.

PMID- 7640974
TI  - Prevalence and impact of wrist and shoulder pain in patients with spinal cord
      injury.
AB  - Spinal cord injury (SCI) patients experience varying degrees of wrist and
      shoulder pain. Previous studies indicated that 30 to 64 percent of SCI patients
      reported chronic shoulder pain. The purpose of this study was to identify the
      prevalence of chronic wrist and shoulder pain, to determine which activities
      caused or exacerbated the pain, and assess functional and emotional responses to
      chronic pain and identify ways in which the pain might be reduced. Eight hundred
      SCI patients were surveyed by questionnaire with 451 (66 percent) responding. In
      addition, 30 patients were available for clinical observation and evaluation.
      Data was evaluated using the Statistical Analysis System and the Cornell Personal
      Adjustment Scale. Results indicated that wrist and shoulder pain were more
      prevalent than previously indicated (72.7 percent of respondents reported some
      degree of chronic pain in one or both of these areas), wheelchair propulsion and
      transfers caused most pain and also increased the degree of pain. Patient's age,
      neurologic level and time since injury were not statistically significant in the
      study and emotional responses did not significantly vary between groups with and
      without pain. Further, it was noted that among the pain group, various routine
      therapies were not effective. We conclude that alternative methods for wheelchair
      propulsion and transfers, which lessen stress and cumulative trauma, need to be
      developed for SCI patients in order to diminish the incidence of chronic upper
      limb pain.

PMID- 7640975
TI  - American Spinal Injury Association annual meeting. Abstracts.

PMID- 7640976
TI  - Maggot therapy for treating pressure ulcers in spinal cord injury patients.
AB  - For centuries, maggot therapy (MT) has been recognized as an aid to wound
      healing. By including live blowfly larvae in wound dressings, earlier physicians
      noted thorough debridement which hastened wound healing. We initiated a
      prospective controlled study to evaluate the utility of maggot therapy for
      treating pressure ulcers in spinal cord injury patients in the modern era. Eight
      of our patients received MT after a baseline assessment of healing under
      conventional therapy (defined as any therapy prescribed by the patient's primary
      care team). Surface area, tissue quality and healing rates were monitored weekly.
      MT debrided most of the necrotic wounds within one week, which was more rapid
      than all other non-surgical methods. Wound healing was more rapid during MT than
      during antecedent conventional therapy (p = 0.01). No complications were seen. We
      have demonstrated that MT can be beneficial in the treatment of pressure ulcers
      in persons with spinal cord injuries. MT was significantly more effective and
      efficient than the current, conventional treatment alternatives being used. MT
      was also safe, simple and inexpensive. MT can be a valuable modality in the
      treatment of pressure ulcers.

PMID- 7640977
TI  - Autonomic dysreflexia revisited.
AB  - Autonomic dysreflexia (AD) is a clinical phenomenon that affects patients with
      spinal cord injury (SCI) above the major sympathetic outflow tract. The lesion is
      most often at or above the T-6 level. Any noxious stimuli below this level
      initiate reflex sympathetic activity resulting in life threatening hypertension
      uncontrollable by the feedback parasympathetic activity. The episodes of
      hypertension generally persist until the offending stimulus is removed. Absence
      of higher control over reflex sympathetic activity due to transection of the cord
      is an anatomical explanation of the phenomenon. Current evidence suggests
      additional factors such as supersensitivity and possibly increased numbers of
      spinal alpha adrenoreceptors and peripheral microvascular adrenoreceptors as well
      as accumulation of substance P below the lesion. It has been suggested that
      substance P acts as a modulator, initiating the sympathetic event to produce a
      strong, slow and prolonged excitatory action. Autonomic dysreflexia is further
      accentuated by the absence of gamma amino benzoic acid (GABA), norepinephrine
      (NE) and 5-hydroxytryptamine (5-HT) below the lesion. GABA is an inhibitory
      neurotransmitter. It has been suggested that either NE or 5-HT may also act as an
      inhibitory neurotransmitter. Resetting of the baroreceptors at a lower level also
      plays an important role. The anatomical transection at or above T-6 then helps in
      maintaining and accentuating the biochemical changes that develop in patients
      with high spinal cord lesions. The current article reviews the pathophysiology
      and management of this potentially life threatening, yet easily treatable,
      phenomenon.

PMID- 7640978
TI  - Management of sphincter dyssynergia using the sphincter stent prosthesis in
      chronically catheterized SCI men.
AB  - This effort represents a subset analysis of the long-term Multicenter North
      American Trial of the UroLume sphincter stent prosthesis to determine the effect
      of the sphincter stent prosthesis in SCI men afflicted with detrusor-external
      sphincter dyssynergia (DESD) and chronically managed with an indwelling urinary
      catheter. Forty-one of 153 male patients in this study were evaluated
      urodynamically before and after placement of the sphincter stent prosthesis. Of
      the 41 patients, 34 (81 percent) suffered cervical-level injury while 10 patients
      (25 percent) had been treated previously with external sphincterotomy. Forty
      patients (98 percent) were troubled with recurrent urinary tract infections
      (UTI), with a mean of 4.6 +/- 3 episodes of UTI per year. Seven patients (17
      percent) demonstrated hydronephrosis prior to stent placement. Follow-up ranged
      from six to 44 months. Voiding pressures decreased from a mean of 77 +/- 23 cmH2O
      preoperatively to 35 +/- 18 cmH2O at 12 months (n = 34) and 33 +/- 20 cmH2O at 24
      months (n = 22) after stent insertion (p = 0.001). Post-void residual urinary
      volume decreased from 202 +/- 187 ml preinsertion to 64 +/- 69 ml at 24 months (p
      = 0.001) postinsertion. Maximum cystometric capacity remained constant at 201 +/-
      144 ml preinsertion to 203 +/- 79 ml at 24 months (p = 0.75) postinsertion. No
      significant changes in any of the urodynamic parameters occurred after 24 months
      of follow-up between patients with (n = 10) and without (n = 31) previous
      external sphincterotomy. Neither hemorrhage requiring blood transfusion,
      obstructive hyperplastic epithelial overgrowth, stent encrustation or stone
      formation, nor soft tissue erosion occurred in any patient.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7640979
TI  - Upper extremity neuropathies in patients with spinal cord injuries.
AB  - We present a cross-sectional study designed to screen and evaluate 19 male
      patients with acute or chronic spinal cord injury for the presence of carpal
      tunnel syndrome (CTS) and radial neuropathies (RNP) in order to establish the
      prevalence of CTS and RNP, to compare characteristics of persons with spinal cord
      injury who do not have these neuropathies, to evaluate the effects of their
      activities and to define the causation of these neuropathies in order to prevent
      their occurrence during and after the rehabilitation process. Patients admitted
      to the Spinal Cord Injury Service with acute and chronic spinal injury (below C3)
      were included in the study. The level of activity was determined with the
      Functional Independence Measure (FIM) Score. Patients underwent neurological
      examination. Neurophysiological studies were done in all cases to determine the
      presence, nature and duration of CTS and RNP. As longevity of the spinal cord
      injured population is increasing, heightened awareness of the prevalence of CTS
      and RNP are necessary to develop strategies to prevent and manage these
      neuropathies which may adversely affect the patient's quality of life. Of 19
      patients studied, three had clinical CTS, confirmed by neurophysiological had no
      neuropathies and five had non-CTS neuropathies. No RNP was found, but one patient
      in the non-CTS group had symptomatic left ulnar neuropathy also confirmed by
      neurophysiological exam.

PMID- 7640980
TI  - Direct bladder stimulation with percutaneous electrodes and impedance monitoring
      of volume in an SCI animal model.
AB  - Bladder responses to percutaneous electrodes were investigated with stimulation
      in three male spinal cats. The animals had been spinalized (T1 level lesion) 10
      weeks prior to these studies and had been instrumented with chronic bladder had
      been spinalized (T1 level lesion) 10 weeks prior to these studies and had been
      instrumented with chronic bladder wall electrodes and suprapubic bladder
      catheters for filling and pressure recording. percutaneous stimulation in
      tethered animals was conducted wit hook electrodes inserted with a needle in the
      abdomen bilaterally adjacent to the bladder trigone. Stimulation was conducted
      with 40 Hz pulse trains of 10 to 30 mA for three seconds. Stimulation with both
      percutaneous and chronic electrodes induced high bladder pressures and voiding.
      In addition, with chronically implanted electrodes, impedance monitoring of
      bladder volume was found to be an effective recording technique.

PMID- 7640981
TI  - Demand management: enabling patients to use medical care appropriately.
AB  - A rationale is presented for considering demand management as well as supply
      management (managed care) in the current debate on health care reform. Demand
      management is the support of individuals so that they may make rational health
      and medical decisions based on a consideration of benefits and risks. The concept
      of demand for medical services is examined within a theoretical framework of four
      components: morbidity, perceived need, patient preference, and nonhealth motives.
      Two components, perceived need and patient preference, are suggested to offer
      considerable potential for making utilization more appropriate and reducing
      costs. Current demand services and potential hazards related to their continued
      expansion are discussed.

PMID- 7640982
TI  - Prevention and managed care: the next generation.
AB  - As we stand at the doorway to the twenty-first century, we are witnessing the
      restructuring of American health care from a fragmented cottage industry to an
      actual health care system. This new system is emerging from a foundation of
      managed care and will be built upon the pillars of prevention. One of the reasons
      this phenomenon is occurring so rapidly is that capitated managed care shifts to
      providers the financial risk for the health care needs of an enrolled population.
      Once providers accept financial risk, it is imperative to assess and manage the
      medical, health, and economic risks of the enrolled population. Under these
      incentives, quality-driven, cost-effective care takes on new meaning to
      physicians. In fact, this new managed care environment begins to merge personal
      health and public health in such a way that the delivery system will begin to
      provide personal-based health care from a population-based perspective.
      Furthermore, the incentives and rewards for maintaining the health of a
      population will finally be present.

PMID- 7640983
TI  - An expert system based preventive medicine examination adviser.
AB  - Periodic preventive medicine examinations generally rely on a standardized
      approach. In addition, they are often performed by physicians with only limited
      training in preventive medicine. Evaluation of a corporate-based program led to
      the prototype development of an artificial intelligence (AI)-based expert system
      to collect information from employees and make very specific recommendations for
      primary practitioners. Unique features include the customizing of questions for
      each subject and the selection of information to be acquired, both based on
      answers to previous questions. Recommendations are highly person specific and
      fall into four categories: laboratory testing, primary physician testing,
      counseling, and referral. The AI approach allows for easy updating of
      recommendations in order to meet changes in local preventive resources and
      national recommendations.

PMID- 7640984
TI  - Fatal farm injuries: a five-year study utilizing a unique surveillance approach
      to investigate the concordance of reporting between two data sources.
AB  - The agricultural industry has been ranked among the most hazardous. Yet, it has
      been alleged that occupational injuries and fatalities are seriously
      underreported. Access to quality agricultural injury data poses a special
      problem. The purpose of this study was to investigate the concordance of
      reporting of fatal agricultural injuries between death certificate data and the
      Newspaper Clipping Service data in the state of Minnesota, utilizing a
      surveillance system developed by the University of Minnesota. Between September
      1, 1981, and August 31, 1986, a total of 350 agricultural fatalities were
      identified in Minnesota; 82% were identified through death certificate data and
      67% through the Newspaper Clipping Service. Differences in reporting between the
      two data sources were noted for gender, age, injury type, anatomical site,
      source, mechanism of injury, and multiple versus single injury. If only death
      certificates had been utilized, 18% of the fatalities would have been missed.
      Although it is apparent that death certificate data have an advantage over the
      Newspaper Clipping Service data for fatality reporting of specific variables,
      this study revealed that death certificate surveillance alone will miss mortality
      data and detection of certain potential risk factors. Suggestions for improving
      surveillance of agricultural fatalities are identified. However, until relevant
      changes are made, it will be essential to use a combination of data sources that
      include the Newspaper Clipping Service to identify agricultural injury fatalities
      accurately.

PMID- 7640985
TI  - Medical surveillance practices of blue collar and white collar hazardous waste
      workers.
AB  - Given the occupational risks of hazardous waste workers, this study was conducted
      to explore possible differences in medical surveillance practices among blue and
      white collar workers. Demographic and medical surveillance data were collected
      from 636 white collar and 206 blue collar trainees, enrolled in health and safety
      training courses. Overall, 4.5% of the trainees reported being ill or injured
      because of hazardous substances. Significant differences (P < .0001) were noted
      between groups; blue collar trainees were more likely to have been ill or
      injured. Differences also existed for medical surveillance enrollment; 32% of the
      white collar trainees report enrollment compared to 19% of the blue collar
      trainees (P = .004). This study indicates that blue collar trainees are more
      likely to be injured and less likely to be enrolled in medical surveillance
      programs. Issues of illness and injury, as well as medical surveillance
      enrollment, must be addressed; ensuring that all workers receive medical
      surveillance needed to prevent occupational illness in the hazardous waste field.

PMID- 7640987
TI  - ACOEM position on the confidentiality of medical information in the workplace.

PMID- 7640986
TI  - The confidentiality of medical information in the workplace.
AB  - Ethical dilemmas involving confidentiality issues are frequently encountered in
      occupational medicine. The occupational physician faces a unique challenge
      because in many circumstances, a physician-patient relationship, in the ordinary
      or legal sense, may not exist. The occupational physician often faces a
      conflicting interest between the employees' desire for privacy and the employer's
      legitimate need to know. The occupational physician must carefully balance these
      interests for the benefit of society and the parties involved. Occupational
      physicians also work in a wide variety of practice situations, and the ethical
      and legal duty of confidentiality may vary substantially with these roles. This
      article provides an overview of the ethical and legal requirements of
      confidentiality in the workplace. The constitutional, statutory, and common law
      framework governing the treatment of employee medical information, as well as
      defenses to liability, are discussed. Recent legislative changes such as the
      Americans with Disabilities Act, and new challenges such as the proper handling
      of HIV information, present unique confidentiality problems.

PMID- 7640988
TI  - Occupationally related cancer risk among coke oven workers: 30 years of follow
      up.
AB  - This study concerns the update of cause-specific mortality among coke oven
      workers. Updated information provides 3 decades of work history and vital status
      follow-up on 15,818 workers. Mortality patterns are summarized by race,
      cumulative exposure, and period of follow-up. The findings are consistent with
      those from earlier assessments, indicating that occupational exposure to coke
      oven emissions is associated with significant excess mortality from cancer of the
      respiratory system and of the prostate. Depending on the segment of the
      population considered, the respiratory cancer risk for coke oven workers ranged
      as high as 4.45 times that for non-oven workers. Relative risk values for cancer
      of the prostate ranged as high as 1.93. Rates of respiratory cancer across period
      of follow-up are declining, suggesting that the implementation of emissions
      control and occupational exposure limits has been beneficial.

PMID- 7640989
TI  - Health information privacy reform.
AB  - Statutory protection for personal health information privacy is in clear need of
      reform. With few exceptions, current legal safeguards provide uneven coverage and
      limited protection. Absence of a uniform federal code of fair health information
      practices leaves individual rights in health information compromised, exposes
      data users, and poses a potential threat to the integrity of the data. Current
      legislative proposals for national health care reform seek to standardize privacy
      protection while simultaneously facilitating usage of personal health information
      in an electronic data network. Reform provisions for confidentiality of health
      data will establish explicit duties for "health information trustees" and should
      strengthen privacy safeguards in the workplace.

PMID- 7640990
TI  - Risk management and recovered memories.

PMID- 7640991
TI  - A grain of sand.

PMID- 7640992
TI  - Effectiveness of diagnosis-related groups in predicting psychiatric resource
      utilization in the U.K.

PMID- 7640993
TI  - Recurring themes and a tribute.

PMID- 7640994
TI  - Psychiatric consultation in the general hospital emergency department.

PMID- 7640995
TI  - When doctors face cancer, and when patients face death.

PMID- 7640996
TI  - Suicide among elderly persons.

PMID- 7640997
TI  - Testing the limits of deinstitutionalization.
AB  - OBJECTIVE: From 1978 to 1993, under favorable administrative and political
      conditions and protected by a court-ordered consent decree, a comprehensive
      community-based mental health system was established in western Massachusetts
      that entirely replaced Northampton State Hospital. This paper examines that
      experience to describe the characteristics and comparative department of mental
      health expenditures on alternative treatment settings and to explore whether the
      need for state hospitals can be eliminated. METHODS: Data on distribution and
      department of mental health funding of services in western Massachusetts were
      compared with similar data from the rest of the state, where state hospital
      utilization remained relatively high. RESULTS: Between 1978 and 1992, department
      of mental health expenditures on noninpatient community services in western
      Massachusetts increased from 15 percent to 74 percent of total expenditures on
      adult mental health services. In 1992 per capita expenditures on such services in
      western Massachusetts and the rest of the state were similar. However, per capita
      expenditures for inpatient services constituted 27 percent of total expenditures
      in western Massachusetts, compared with 53 percent in the rest of the state.
      Western Massachusetts spent approximately twice as much per capita on residential
      and emergency services and one and a half times as much on case management
      services and support. Very few Northampton patients were transferred to nursing
      homes, and the inpatient census per 100,000 population supported by the
      department of mental health in western Massachusetts was one-third of that in the
      rest of the state. CONCLUSION: Under certain conditions, the role and functions
      of state hospitals can be completely replaced by a system of comprehensive
      community services.

PMID- 7640998
TI  - A qualitative approach to assessing the effects of system change on consumers,
      families, and providers.
AB  - OBJECTIVE: In 1988 Vermont implemented a policy designed to reduce the state
      hospital census and expand community-based services. This qualitative study
      assessed perceptions of the policy's impact among mental health consumers, family
      members, and providers. METHODS: Eleven focus groups were convened, which
      included 94 participants from across the state. Separate groups were held for
      consumers, family members, and providers. Trained facilitators guided discussion
      of the policy's effect on quality of life, housing and vocational status,
      community integration, and social networks. Audiotapes of the discussion were
      transcribed, and content was analyzed. RESULTS: Several universal themes were
      noted. All participants reported that stigma was still a substantial barrier to
      integration and that community education to reduce stigma had not been effective.
      Tension between families and providers was a problem; family members felt that
      although providers depended on their supporting the consumer, they were not
      included in treatment planning. All participants noted that urban areas were
      better served by the policy's service packages. A lack of coordination of
      community services was reported to be a continuing problem across the state. In
      contrast to findings of previous studies, consumers in this study preferred not
      to live alone, which led to feelings of isolation. CONCLUSIONS: Service delivery
      in rural areas and system coordination throughout the state must be improved.
      Families' conflicting feelings of burden and isolation must be addressed. Further
      research should determine more clearly the range of housing preferences among
      consumers.

PMID- 7640999
TI  - The first 18 months of mental health reform in Kansas.
AB  - OBJECTIVE: The effects of the first 18 months of implementation of the Kansas
      Mental Health Reform Act were evaluated. The act designated community mental
      health centers as gatekeepers for admission to mental health services, created
      screening and diversion services for state hospital admission, allocated state
      hospital bed days to each center, and reallocated funds from hospitals to
      communities. METHODS: Data from the catchment area in which reform was
      implemented in the 18-month study period, January 1991 to June 1992, were
      compared with data for that area before reform, and with data for the two state
      hospital catchment areas in which reform was not yet implemented. RESULTS: In the
      catchment area in which reform was implemented, state hospitalization decreased
      by about 29 percent, and state mental health funds allocated to the area's mental
      health centers almost doubled. Service utilization by patients discharged from
      the state hospital was higher than in the other two catchment areas, and most
      indicators of living status and vocational or educational involvement reflected
      improvement. CONCLUSIONS: The first 18 months of implementation suggest that
      state-level systems change can decrease state hospitalization and improve the
      utilization of community services while improving the quality of life for people
      with severe and persistent mental illness.

PMID- 7641000
TI  - Racial differences in treatment of psychiatric inpatients.
AB  - OBJECTIVE: The study examined several aspects of inpatient psychiatric treatment
      to determine if differences existed between treatment of African-American and
      white patients. METHODS: Using a structured chart review, data were collected on
      76 African-American and 88 white patients consecutively admitted to an acute
      inpatient setting with a principal axis I diagnosis of a major mood or psychotic
      disorder. Racial differences in treatment were examined using analysis of
      variance and logistic regression to assess the effects of diagnosis and
      socioeconomic status. RESULTS: Nonpsychotic African-American patients had shorter
      lengths of stay than white patients with similar disorders. White patients were
      more likely to be on one-to-one observational status. Clinicians were more likely
      to order urine drug screens for African-American patients with high socioeconomic
      status than for comparable white patients. African-American patients with
      schizophrenic disorders received higher neuroleptic dosages than white patients
      with similar diagnoses. CONCLUSIONS: Most racial differences cited in earlier
      studies of psychotic patients were not found or were not statistically
      significant once socio-economic status and diagnosis were accounted for. However,
      racial differences related to the detection, phenomenology, treatment, and course
      of psychotic disorders and the diagnosis and management of alcohol and drug use
      disorders and personality disorders were found.

PMID- 7641001
TI  - Mental illness and substance use among sheltered homeless persons in lower
      density population areas.
AB  - OBJECTIVE: The prevalence of mental illness and substance abuse in homeless
      populations has been studied primarily in large urban areas. This study examines
      a sheltered homeless population in two counties of lower-density population,
      Dauphin and Cumberland counties in central Pennsylvania, to assess the prevalence
      of mental illness and substance abuse. METHODS: A total of 81 homeless adults
      from nine emergency shelters were interviewed using a structured questionnaire.
      RESULTS: The estimated lifetime prevalence rate of major depressive disorder was
      26.6 percent; 6.4 percent of the sample showed evidence of psychotic thinking.
      Almost one-third reported previous hospitalization for emotional problems, and
      about one-third reported a suicide attempt. The estimated lifetime prevalence
      rate of alcohol or drug abuse or dependence was almost 60 percent. CONCLUSIONS:
      Although mental illness, especially psychosis, and substance abuse may be
      somewhat less prevalent among homeless persons in lower-density population areas
      than in large urban areas, they are nevertheless significant problems.

PMID- 7641002
TI  - Base-rate estimates of criminal behavior by homeless mentally ill persons in New
      York City.
AB  - OBJECTIVES: The study aimed to estimate the prevalence of homelessness among
      mentally disordered offenders entering the criminal justice and forensic mental
      health systems, to compare base rates of arrest for violent and nonviolent
      criminal charges among homeless and domiciled persons with mental illness, and to
      examine patterns in the categories of victims chosen by these two groups.
      METHODS: The authors analyzed data from structured psychiatric interviews and
      criminal and psychiatric records of 77 homeless defendants and 107 domiciled
      defendants referred for psychiatric examination by the criminal and supreme
      courts in Manhattan over a six-month period. RESULTS: Mentally disordered
      defendants had 40 times the rate of homelessness found in the general population,
      and 21 times the rate in the population of mentally ill persons in the city. The
      overall rate of criminal offenses was 35 times higher in the homeless mentally
      ill population than in the domiciled mentally ill population. The rate of violent
      crimes was 40 times higher and the rate of nonviolent crimes 27 times higher in
      the homeless population. Homeless defendants were significantly more likely to
      have been charged with victimizing strangers. CONCLUSIONS: Homeless mentally ill
      persons appear to be grossly overrepresented among mentally disordered defendants
      entering the criminal justice and forensic mental health systems and to have a
      higher base rate of arrest for both violent and nonviolent crimes than domiciled
      mentally ill persons.

PMID- 7641003
TI  - Modifying the PACT model: preserving critical elements.
AB  - Few agencies have the resources to replicate the Program for Assertive Community
      Treatment (PACT) model pioneered in Madison, Wisconsin, which calls for around
      the-clock, comprehensive treatment and rehabilitation services for persons with
      serious mental illness. Most agencies modify the model program, and little is
      known about patient outcomes in such altered programs. This paper discusses
      issues in modifying the PACT model, especially for use in rural areas. The
      authors focus on six basic elements of the PACT model: multiservice teams, 24
      hour service availability, small caseloads that do not vary in composition,
      ongoing and continuous services, assertive outreach, and in vivo rehabilitation.
      They describe how programs in South Carolina that are adaptations of the PACT
      model have retained these elements and achieved desired outcomes with smaller
      teams operating on modified schedules.

PMID- 7641004
TI  - Characteristics of effective day treatment programming for persons with
      borderline personality disorder.
AB  - Day treatment, or partial hospitalization, may have unique advantages for the
      treatment of patients with borderline personality disorder. Such treatment may
      offer patients the optimal level of intensiveness and containment, resulting in
      less regressive dependency and acting-out behavior. To be successful in treatment
      of patients with borderline personality disorder, a day treatment program should
      facilitate the patient's need to experience and express affect safely, optimize
      the program's ability to provide less restrictiveness than inpatient treatment
      but more sustained and intensive support than outpatient treatment, and use
      verbal and nonverbal approaches to help patients maintain primary responsibility
      for their well-being. A length of stay of three weeks allows patients to regain
      baseline functioning and resume long-term outpatient care. Treatment goals should
      be clear and resolvable in three weeks.

PMID- 7641005
TI  - The relationship between nurses' limit-setting styles and anger in psychiatric
      inpatients.
AB  - OBJECTIVE: Violence by patients in psychiatric settings is frequently associated
      with the quality of staff-patient interactions. Impulsivity has been identified
      as a high risk factor for anger and aggression. This study was designed to test
      the influence of nurses' limit-setting styles on anger among psychiatric
      inpatients grouped by high or low levels of impulsivity. METHODS: Ninety-seven
      patients with various diagnoses and either high or low levels of impulsivity
      participated in role-play scenarios in which nurse actors played out six limit
      setting styles, ranging from belittlement to explanations of rules to empathy
      linked with a presentation of an alternative course of action. Patients' level of
      anger in response to the acted scenario was assessed using the Spielberger State
      Trait Anger Scale. RESULTS: Patients' level of anger was highest in response to
      unempathic limit-setting styles, moderate for explanations, and lowest for
      empathic styles. Impulsive subjects were more likely to respond with anger than
      nonimpulsive patients, regardless of the limit-setting style. CONCLUSIONS:
      Although many current intervention programs focus on reducing patients' anger
      after it occurs, the study results suggest that it may be possible to prevent
      some of patients' anger by improving nurses' limit-setting styles.

PMID- 7641006
TI  - Psychiatric patients' explanations for assaults.
AB  - Using videocameras, the authors detected 134 assaults by 40 of 113 patients
      treated over a 23-month period on a 14-bed intensive ward for violent psychiatric
      patients. After assailants were approached by an interviewer to obtain their
      explanations for the assaults, investigators analyzed the content of their
      responses by assigning up to four themes to each response. Most frequently the
      patient refused to be interviewed. Assailants who cooperated often claimed to
      have been playing with the victim, complained of verbal abuse, or said they
      wanted to stop objectionable behaviors by the victim. The results suggest that
      assailants may perceive some behaviors by victims as provocations.

PMID- 7641007
TI  - Training health professionals in the recognition and treatment of depression.
AB  - A total of 423 health professionals, including physicians, psychologists,
      counselors, social workers, and nurses, attended a two-day program to increase
      awareness, recognition, and treatment of depression. In a preprogram opinion
      survey, nurses and social workers reported less perceived ability to recognize
      mood disorders compared with physicians and psychologists. In a group of 274
      respondents who took a 20-item test of their knowledge about depression before
      and after attending the program, scores for all professions increased after the
      program and pretest differences in scores between professions decreased. The
      results suggest that training was successful in increasing knowledge about
      depression among a diverse group of health professionals.

PMID- 7641008
TI  - Identifying anxiety disorders in adolescents hospitalized for alcohol abuse or
      dependence.
AB  - In structured clinical interviews of 43 adolescents hospitalized for alcohol
      abuse or dependence, 17 subjects met criteria for an anxiety disorder, with
      social phobia (N = 9) and posttraumatic stress disorder (N = 7) most common. Of
      these 17 subjects, only four were identified in hospital records as having an
      anxiety disorder. In a comparison of 30 hospitalized adolescents with a matched
      control group of 30 adolescents from the community, the hospitalized adolescents
      had a higher rate of anxiety disorders, psychoactive substance use disorders,
      disruptive behavior disorders, and mood disorders.

PMID- 7641009
TI  - Characteristics of police referrals to a psychiatric emergency unit in Australia.
AB  - The study examined characteristics of patients referred by police to a
      psychiatric emergency unit on the campus of a 400-bed psychiatric hospital in
      Adelaide, South Australia. Of all police referrals (N = 634) during a 21-month
      period, 437 cases were admitted to the hospital. Most police referrals were
      young, single, unemployed men. In a subsample of 61 patients, 72 percent had
      previous psychiatric admissions and 39 percent had been previously referred by
      police. Compared with nonpsychotic subjects, psychotic subjects used more mental
      health resources, had a longer index admission, and after the index discharge
      relapsed more rapidly and spent more days in the hospital.

PMID- 7641010
TI  - Hospital ethics committees.

PMID- 7641011
TI  - Medications in emergencies.

PMID- 7641012
TI  - The needle biopsy should replace open excisional biopsy ... but will the
      surgeon's role in coordinating breast cancer treatment be diminished?

PMID- 7641013
TI  - Should axillary dissection be performed in patients with DCIS?

PMID- 7641015
TI  - Analysis of residual cancer after diagnostic breast biopsy: an argument for fine
      needle aspiration cytology.
AB  - BACKGROUND: Diagnostic breast biopsy (DxBx) requires an effective strategy for
      successful treatment of breast cancer by lumpectomy or mastectomy. Clearance of
      margins is required to achieve local control. METHODS: We reviewed 844 malignant
      diagnostic biopsies. The strategy was to perform DxBx on all nonpalpable lesions
      and fine-needle aspiration (FNA) on all palpable lesions. When FNA was equivocal,
      DxBx was performed. After positive DxBx, either the biopsy cavity or FNA-positive
      breast mass was excised, and margins were documented with touch preparation
      cytology analysis (TPC) and frozen section (FS) as necessary to achieve negative
      margins. RESULTS: Outside institutions referred 430 excisional biopsies. Two
      hundred twenty-five (52.3%) were found to have residual cancer at surgical
      excision. Our institution performed 414 biopsies: 169 were performed on
      nonpalpable lesions in which 58% had residual tumor at resection; 245 were
      diagnosed by FNA of palpable lesions. Residual disease was found in 12 (5%).
      CONCLUSIONS: Of patients who undergo DxBx, > 50% have residual breast cancer. It
      is recommended that (a) FNA be performed on all palpable masses or DxBx of
      nonpalpable masses; when cancer is diagnosed, proceed to surgical excision. (b)
      When lumpectomy is the option, margins should be reexcised and intraoperatively
      evaluated with TPC and FS at the time of axillary dissection.

PMID- 7641014
TI  - Stereotactic breast biopsy as an alternative to open excisional biopsy.
AB  - BACKGROUND: Health care cost continues to play a dominant role in our society.
      Technological advances are expensive, with the possible exception of stereotactic
      breast biopsy. We must learn other alternatives that give the same diagnostic
      accuracy at lower cost. The intention of this study was to find other acceptable
      alternatives to open excisional breast biopsies. METHODS: Patients were referred
      to Baylor University Medical Center between May 1990 and June 1992 for
      stereotactic breast biopsy of nonpalpable mammographic abnormalities. Before
      stereotactic biopsy, lesions were categorized into low or high suspicion for
      malignancy based on screening mammography. Slides were reviewed by a pathologist
      and the histological diagnosis was compared with mammographic characterization.
      Benign histology confirming the low-suspicion mammographic abnormality
      demonstrated mammographic and histologic correlation. Mammographic follow-up was
      recommended. RESULTS: Two hundred twenty-five women underwent 250 stereotactic
      breast biopsies. Malignancy was diagnosed in 47 patients; the remaining 203
      lesions were benign on pathological examination and are being followed regularly.
      Seventy-eight percent of the lesions were characterized as low suspicion for
      malignancy, and 22% were characterized as high suspicion. The average cost
      savings per lesion using stereotactic biopsy was $1,629. CONCLUSION: Stereotactic
      breast biopsy is an acceptable, less expensive alternative to open excisional
      biopsy for diagnosing nonpalpable mammographic findings.

PMID- 7641016
TI  - Treatment trends for ductal carcinoma in situ of the breast.
AB  - BACKGROUND: As a result of clinical trial publications, breast conservation
      treatment has been increasingly used for invasive breast cancer. The patterns of
      care for ductal carcinoma in situ (DCIS) were analyzed for the years 1985, 1986,
      1988, 1990, and 1991 to determine whether the same treatment principles had been
      applied to patients with non-invasive disease. METHODS: Data submitted on 20,556
      patients with DCIS during the 5 study years were analyzed with regard to basic
      demographics and treatment trends. RESULTS: Breast-conserving surgery for DCIS
      increased from 20.9% in 1985 to 35.4% in 1991. Modified radical mastectomy
      remained constant at 42%. Axillary node surgery increased from 52% in 1985 to
      58.5% in 1991. The use of radiation therapy for patients with partial mastectomy
      and no lymph node dissection ranges from 24.2% in 1990 to 37.7% in 1985, with
      31.1% receiving radiation therapy in 1991. Patients undergoing lymph node
      dissection with partial mastectomy were more than twice as likely to receive
      postoperative radiation therapy than were patients without lymph node dissection.
      CONCLUSIONS: Modified radical mastectomy remains the most common surgical
      procedure, despite the eligibility of many women for breast conservation
      treatment. As of 1991 the majority of women were still undergoing axillary lymph
      node surgery despite a node positivity rate of approximately 1%. Radiation
      therapy is significantly underused in patients with partial mastectomy,
      especially when no nodes were removed. Clinical trial results and professional
      education for DCIS treatment should change these trends.

PMID- 7641017
TI  - A phase II trial investigating primary immunochemotherapy for malignant pleural
      mesothelioma and the feasibility of adjuvant immunochemotherapy after maximal
      cytoreduction.
AB  - BACKGROUND: The treatment of malignant pleural mesothelioma (MPM) continues to be
      inadequate with the use of standard techniques, including surgery, radiotherapy
      and chemotherapy. We initiated a phase II trial of immunochemotherapy with
      cisplatinum (25 mg/m2 four times weekly), interferon-alpha (5 mU/m2 s.c. three
      times weekly, and tamoxifen (20 mg orally twice a day for 35 days) (CIT) based on
      in vitro and in vivo data suggesting interrelating efficacy of this combination.
      METHODS: Since July 1991, 36 patients have been evaluable for response after
      receiving one to five cycles of CIT. Ten additional patients had debulking
      surgery followed by two cycles of postoperative adjuvant CIT commencing a mean of
      6 weeks after surgery. RESULTS: Toxicity was acceptable (4% grade III/IV). One
      treatment-related death (2%) occurred, from myocardial infarction. A 19% partial
      response rate, objectively quantified using three-dimensional computerized
      tomographic (CT) measurement of solid disease volume, was recorded. The median
      survival for the seven responders was 14.7 months, whereas that of the
      nonresponders was 8 months (p2 = 0.2). Median survival for the entire group was
      8.7 months. Preoperative size, platelet count > 360,000/ml, and nonepithelial
      histology were associated with shortened survival. CONCLUSIONS: The CIT regimen
      has some activity in MPM and can be delivered after debulking resection. In good
      risk patients, as defined by favorable prognostic factors, a randomized trial
      using this combination may be warranted.

PMID- 7641018
TI  - Radical and local excisional methods of sphincter-sparing surgery after high-dose
      radiation for cancer of the distal 3 cm of the rectum.
AB  - BACKGROUND: Despite conventional attitudes that interdict sphincter-preservation
      surgery (SPS) for cancers arising in the terminal 3 cm of rectum, we have
      selectively employed high-dose preoperative external radiation (HDPER) and either
      radical or local excisional SPS techniques for rectal cancer arising between the
      0.5 and 3 cm levels above the anorectal ring. We have reported a preliminary
      experience with HDPER and full-thickness local excision (FTLE) and three
      different methods of radical SPS. We now describe our experience with a single
      method of radical excision, transanal abdominal transanal proctosigmoidectomy
      with coloanal anastomosis (TATA) and FTLE in conjunction with HDPER for cancers
      of the distal 3 cm of rectum based on specific guidelines. METHODS: Since 1984,
      109 patients with cancers at or below the 3 cm level have been treated with HDPER
      in doses of 4,500-7,000 cGy and a sphincter-preserving radical or local excision
      method in a prospective rectal cancer management program. Sixty-five patients
      (group A) underwent transanal abdominal transanal radical proctosigmoidectomy
      with colonal anastomosis (TATA) and 44 patients (group B) underwent FTLE.
      RESULTS: There was one death (1%). Mean follow-up was 40 months. Local recurrence
      rates for groups A and B were 9 and 14%, respectively. Kaplan-Meier 5-year
      actuarial survival was 85 and 90% for groups A and B, respectively, and 87%
      collectively. CONCLUSION: Experience with 109 patients with cancers of the distal
      3 cm of rectum indicates that SPS can be accomplished by either radical or local
      excisional methods with acceptable local control and survival if HDPER and strict
      selection guidelines are employed.

PMID- 7641019
TI  - Intraoperative photodynamic therapy as an adjunct to surgery for recurrent rectal
      cancer.
AB  - BACKGROUND: Locally recurrent rectal cancer is a difficult management problem for
      the surgical oncologist. Current therapies including radical surgery, radiation
      and chemotherapy have had little success in producing curative results for these
      patients. This study incorporated intraoperative photodynamic therapy (PDT) as an
      adjunct to radical surgery for the treatment of locally recurrent rectal cancer.
      METHODS: Twenty-two patients were enrolled in a prospective feasibility study and
      injected with Photofrin (Quadra Logic Technologies, Vancouver, British Columbia,
      Canada) before surgery. Eight patients were found to be candidates and received
      PDT after surgical exploration and resection. Seven patients had rectal
      adenocarcinoma and one had squamous cell carcinoma of the anal canal. RESULTS:
      Based on the indication for PDT, three patient groups were evaluated: group A,
      resection of all gross disease with negative pathologic margins in four patients;
      group B, resection of gross disease with positive pathologic margins in two; and
      group C, residual bulky tumor in two patients. There was one perioperative death
      (12.5%), not related to PDT, and one major morbidity due to PDT (12.5%). Local
      recurrence occurred in six patients (two in group A, two in group B, two in group
      C). Mean overall survival was 15.4 months for group A, 6.5 months for group B,
      and 24.5 months for group C. CONCLUSIONS: The results of this study suggest that
      intraoperative PDT may be administered safely in patients undergoing resection of
      recurrent rectal cancer. However, its use in the present state of technology
      appears to be inadequate for control of disease, particularly if bulky tumor or
      residual microscopic disease is left behind.

PMID- 7641020
TI  - Characterization of the neoplastic potential of solitary solid thyroid lesions
      with Tc-99m-pertechnetate and Tc-99m-sestamibi scanning.
AB  - BACKGROUND: Radionuclide scans that use Tc-99m-pertechnetate or I-123 currently
      lack the specificity to assess the malignant potential of solitary solid lesions
      of the thyroid gland. Tc-99m-sestamibi scanning was used to determine the
      neoplastic potential of thyroid lesions. METHODS: Patients with lesions of the
      thyroid underwent Tc-99m-sestamibi imaging to assess the neoplastic potential of
      their thyroid lesions, identified as solitary and cold by radionuclide imaging
      with Tc-99m-pertechnetate. Tc-99m-sestamibi uptake was correlated with fine
      needle aspiration cytology or surgical pathology. RESULTS: Twenty-seven patients
      were evaluated using Tc-99m-pertechnetate and Tc-99m-sestamibi scans: 14 had
      right thyroid lesions, and 13 had left thyroid lesions. Of 27 patients, 10 had a
      positive Tc-99m-sestamibi scan: one Hurthle cell adenoma, one papillary
      carcinoma, six follicular adenomas, and two nodular goiters. Of 27 patients, 17
      had a negative Tc-99m-sestamibi scan: one follicular carcinoma, one papillary
      carcinoma, two follicular adenomas, one Hurthle cell adenoma, one metastatic
      adenocarcinoma, one medullary carcinoma, four nodular goiters, and six colloid
      nodules. Positive Tc-99m-sestamibi scan identified neoplasms with a sensitivity
      of 53%, a specificity of 83%, and a positive predictive value of 80%.
      CONCLUSIONS: Tc-99m-sestamibi scanning lacks sufficient sensitivity for diagnosis
      of solitary thyroid nodules. Future work may define a role for its use in
      recurrent or metastatic thyroid neoplasms.

PMID- 7641021
TI  - Effects of tamoxifen on growth and apoptosis of estrogen-dependent and 
      independent human breast cancer cells.
AB  - BACKGROUND: Apoptosis ("programmed cell death") is an active process
      characterized by prominent nuclear changes and DNA cleavage, which distinguishes
      it from cellular necrosis. In this study we investigated whether tamoxifen (TAM)
      treatment of estrogen receptor ER(+) MCF-7 and ER(-) MDA-231 human breast cancer
      cells resulted in cytotoxicity and cellular changes typical of apoptosis.
      METHODS: Cytotoxicity was measured using a tetrazolium assay. Cellular
      morphologic changes were observed using transmission electron microscopy. DNA
      cleavage was assessed using 1.6% agarose gel electrophoresis and was also
      quantitated biochemically. RESULTS: Exposure of cells to TAM for 24 h resulted in
      dose-dependent cytotoxicity, and MCF-7 cells were somewhat more sensitive to TAM.
      TAM induced chromatin condensation around the nuclear periphery in both cell
      lines, changes typical of apoptosis. TAM-induced cytotoxicity correlated with
      dose-dependent DNA cleavage, which showed the characteristic "internucleosomal
      ladder." DNA cleavage occurred at a slightly lower TAM dose and occurred somewhat
      sooner in MCF-7 cells. TAM-induced DNA cleavage in MCF-7 cells was inhibited by
      the protein synthesis inhibitor cycloheximide, the RNA synthesis inhibitor
      actinomycin D, and by 17 beta-estradiol. However, in MDA-231 cells, DNA cleavage
      was inhibited by cycloheximide, partially but not significantly inhibited by
      actinomycin D, and not inhibited by 17 beta-estradiol. CONCLUSIONS: TAM induces
      typical apoptosis in ER(+) or ER(-) human breast cancer cells. TAM induction of
      apoptosis in MCF-7 cells involves the estrogen receptor, and requires the
      synthesis of new protein and mRNA. TAM induction of apoptosis in MDA-231 cells
      depends primarily on protein synthesis. TAM-induced cytotoxicity and DNA damage
      appear to be explained in part by the induction of apoptosis.

PMID- 7641022
TI  - Secondary malignancy of the thyroid gland and its management.
AB  - BACKGROUND: Secondary cancer of the thyroid gland is widely acknowledged as
      infrequent but is a persistent problem requiring ongoing awareness, particularly
      with respect to clinical recognition and treatment. METHODS: From 1978 to 1993, a
      15-year period, patients demonstrating secondary involvement of the thyroid gland
      as a surgical problem were collected and analyzed with regard to pathology,
      demography, behavior of primary and secondary disease, treatment, and patient
      outcome. RESULTS: In the 15-year span, 11 patients with secondary involvement of
      the thyroid gland were recognized, consisting of 3 men and 8 women with primary
      lesions occurring in oral cavity, esophagus, stomach, colon, pancreas, breast,
      skin, unknown, kidney, and lung. Needle biopsy produced a 90% malignancy rate but
      in only half of such cases was the diagnosis specific for secondary malignancy.
      Eight of 11 underwent palliative surgery, usually total thyroidectomy. No patient
      survived > 2 years. There was no undue surgical morbidity. One patient died of
      pulmonary embolus postoperatively. CONCLUSIONS: Secondary cancer of the thyroid
      is rare and can be detected by fine-needle aspiration biopsy in the face of
      clinical findings. Where indicated, palliative thyroidectomy can be effective,
      because other methods of treatment appear ineffective.

PMID- 7641023
TI  - Characterization and growth factor stimulation of L-arginine transport in a human
      colon cancer cell line.
AB  - BACKGROUND: Epidermal growth factor (EGF) and transforming growth factor alpha
      (TGF alpha) are potent mitogens that contribute to abnormal growth regulation in
      colon cancer. Growth factors have been shown to regulate transmembrane nutrient
      uptake as an adaptive response to support cellular proliferation. METHODS: The
      transport of L-arginine by the SW480 primary human colon adenocarcinoma cell line
      was characterized by assaying the uptake of [3H]L-arginine in the presence and
      absence of sodium. Kinetic studies were performed over a range of L-arginine
      concentrations to determine transport affinity (Km) and maximal transport
      velocity (Vmax). To further characterize the specific transporters, [3H]L
      arginine uptake was measured in the presence of selected amino acids, hormones,
      and under conditions of varying external pH. To investigate the effects of EGF
      and TGF alpha, cells were incubated with increasing doses of growth factors (1,
      10, 50 ng/ml) and L-arginine transport was measured at various time intervals (8,
      12, 24 h). Proliferation was assessed by the colorimetric 3-(4,5-dimethylthiazol
      2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay 3 days after growth factor
      stimulation. RESULTS: The majority of carrier-mediated L-arginine transport was
      via a sodium-independent process (65-70%), whereas the remainder was sodium
      dependent (28-30%). Diffusion contributed a small amount to total L-arginine
      uptake (2%). Kinetic studies of arginine transport revealed a single high
      affinity Na(+)-independent transporter with a Km = 55.8 +/- 5.8 microM and a Vmax
      = 710.6 +/- 87.3 pM/mg protein/30 s. Na(+)-independent arginine uptake was pH
      insensitive and markedly inhibited by system y+ substrates L-homoarginine, L
      lysine, and L-ornithine. A single Na(+)-dependent transporter with a Km = 19.8 +/
      2.3 microM and a Vmax = 159.1 +/- 8.9 pM/mg protein/30 s was identified. Na(+)
      dependent arginine uptake was inhibited by system BO,+ substrates L-lysine, L
      ornithine, L-leucine, L-cysteine, and L-glutamine, but not by 2
      methylaminoisobutyric acid. In addition, Na(+)-dependent arginine uptake was pH-
      and hormone-insensitive. Incubation with EGF or TGF alpha had no effect on Na(+)
      independent L-arginine uptake; however, Na(+)-dependent uptake was enhanced 60%
      by EGF (10 ng/ml, p < 0.05) and 100% by TGF alpha (10 ng/ml, p < 0.05), whereas
      cellular proliferation was increased 27% by EGF (10 ng/ml, p < 0.05) and 37% by
      TGF alpha (10 ng/ml, p < 0.01). CONCLUSIONS: L-arginine transport in the SW480
      colon cancer cell line is principally mediated by the Na(+)-independent system y+
      and to a lesser extent by the Na(+)-dependent system BO,+. Furthermore, EGF and
      TGF alpha preferentially stimulate L-arginine uptake via the Na(+)-dependent
      transporter, ostensibly to accommodate for the mitogenic stimulus.

PMID- 7641024
TI  - Effect of lovastatin alone and as an adjuvant chemotherapeutic agent on hepatoma
      tissue culture-4 cell growth.
AB  - BACKGROUND: Cholesterol is essential for cell viability and growth. Interference
      with the cholesterol biosynthetic pathway with a 3-hydroxy-3-methylglutaryl
      coenzyme A reductase inhibitor (e.g., lovastatin) may preferentially slow
      malignant cell growth and offer a new approach to cancer chemotherapy. To test
      this hypothesis, we evaluated the effect of lovastatin alone, and as an adjuvant
      chemotherapeutic agent, on the growth and function of hepatoma tissue culture-4
      (HTC-4) cells. METHODS: HTC-4 cells were treated with lovastatin at
      concentrations of 1, 3, 5, and 10 microM, with mitomycin-C at concentrations of
      10, 25, 50, and 100 nM, or with combinations of the two drugs. Cell growth was
      evaluated by daily cell counts and substrate adhesion to fibronectin. RESULTS:
      Lovastatin alone slowed HTC-4 cell growth at concentrations as low as 1 microM (p
      < 0.01). Mitomycin-C alone slowed HTC-4 cell growth at concentrations of 25 nM
      and above (p < 0.01). Lovastatin added to mitomycin-C-treated cells resulted in a
      significant adjuvant effect, with cell growth slowed by an additional 20-30% by 1
      microM lovastatin and by an additional 43-63% by 5 microM lovastatin, compared to
      mitomycin-C alone (p < 0.01). Lovastatin-treated cells also exhibited decreased
      adherence to substrate (p < 0.05). CONCLUSIONS: Lovastatin is effective alone and
      as an adjuvant to mitomycin-C in slowing the growth of HTC-4 cells. These in
      vitro results support further investigation of lovastatin as an adjuvant
      chemotherapeutic agent in animal models.

PMID- 7641026
TI  - Why pharmacists should not sell homeopathic remedies.

PMID- 7641025
TI  - Breast-conserving surgery for breast cancer: patterns of care in a geographic
      region and estimation of potential applicability.
AB  - BACKGROUND: It has been postulated that one of the rewards of breast cancer
      screening is the increased likelihood of receiving breast-conserving surgery. The
      recent wide application of screening mammography has led to an acceleration in
      the otherwise gradual shift toward smaller, earlier-stage breast cancer that has
      been occurring since the turn of the century. METHODS: We examined data from
      patients with pathologically diagnosed breast cancers from all general hospitals
      in the state of Vermont for use of breast-conserving surgery by era (1975-1984 [n
      = 1,652] versus 1989-1990 [n = 683]), method of cancer detection, age, clinical
      tumor-node-metastases (cTNM) stage, pathologic size, and node status. RESULTS:
      Cancers detected by mammography were 2% in 1975-1984 and 36% in 1989-1990.
      Invasive breast cancers < 2 cm maximum pathologic diameter were 34% in 1975-1984
      and 50% in 1989-1990 (p < 0.001). Statewide, the use of breast-conserving surgery
      for invasive cancer increased from 8.6% in 1975-1984 to 42.9% in 1989-1990 (p <
      0.001). In 1989-1990 at the single university hospital, 73% of the patients were
      treated with breast-conserving surgery versus 22% at the community hospitals
      (range 0-39%, p < 0.001). Differential referral patterns related to stage and age
      did not appear to explain the variation, because the percentages of cTNM stage I
      and II patients at the university hospital were similar to those of the community
      hospitals. Using the university hospital as the standard, we estimated that at
      least 67% of all patients in the state were eligible for breast-conserving
      surgery in the years 1975-1984 and 73% in the years 1975-1984, a 6% increase.
      CONCLUSIONS: Most of the variation in breast-conserving surgery was related to
      factors other than patient age and stage of disease. Variation was probably
      related more to local community factors and physician attitudes. At least two
      thirds of the women in the state were eligible for breast-conserving surgery even
      before the wide use of mammography screening.

PMID- 7641027
TI  - Wanted: timely receipt of drug-recall information.

PMID- 7641028
TI  - Wanted: timely receipt of drug-recall information.

PMID- 7641029
TI  - Hepatitis A vaccine gains marketing approval.

PMID- 7641030
TI  - FDA expands access to gemcitabine for pancreatic cancer.

PMID- 7641031
TI  - Zidovudine regimen in pediatric AIDS trial halted, other regimens shown superior.

PMID- 7641032
TI  - Cancer centers form national network.

PMID- 7641034
TI  - Staff development.

PMID- 7641033
TI  - Getting every last drop from ampuls and vials.

PMID- 7641035
TI  - Human immunodeficiency virus infection in children.
AB  - The transmission, diagnosis, and clinical manifestations of human
      immunodeficiency virus (HIV) infection in children up to 13 years of age are
      reviewed, and maintenance and prophylactic drug therapies for these patients are
      discussed. HIV can be transmitted from mother to infant in utero, during
      delivery, or through breast milk. Perinatal transmission accounts for almost 90%
      of all pediatric HIV infections. HIV infection can be diagnosed with HIV
      culturing, polymerase chain reaction testing, the enzyme-linked immunosorbent
      assay, the Western blot antibody assay, or the p24 core-antigen assay. Testing
      should begin as soon as possible after the at-risk child reaches one month of
      age. CD4+ lymphocyte counts are also used in diagnosis and monitoring. The median
      age at diagnosis of AIDS in children with perinatally acquired HIV infection is
      12-24 months. Among the many possible clinical features are Pneumocystis carinii
      pneumonia (PCP), cytomegalovirus infection, failure to thrive, encephalopathy,
      recurrent bacterial infection, thrush, lymphoid interstitial pneumonitis,
      lymphadenopathy, pancreatis, hepatitis, anemia, and thrombocytopenia. Zidovudine
      is considered the drug of choice for initial therapy in HIV-infected children and
      is indicated for asymptomatic infection, early symptomatic disease, and advanced
      disease. However, new research is questioning the role of zidovudine monotherapy.
      Didanosine is the only agent with FDA-approved labeling for use as second-line
      therapy in children who do not respond to or become resistant to zidovudine.
      Agents under investigation for pediatric use are zalcitabine, stavudine,
      lamivudine, and nevirapine. Drug combinations, such as zidovudine plus
      didanosine, are also being examined. Zidovudine appears to reduce the rate of
      maternal transmission of HIV. Agents used prophylactically against PCP in
      children are trimethoprim-sulfamethoxazole, dapsone, and inhaled or i.v.
      pentamidine. HIV-infected children should also received prophylaxis against
      recurrent bacterial infections. The standard pediatric immunization schedule is
      used, but inactivated injectable poliovirus vaccine must be given instead of the
      live oral vaccine. Zidovudine remains the first-line agent for treating HIV
      infection in children. Alternatives are available for those who do not respond to
      zidovudine.

PMID- 7641036
TI  - Pharmacist participation in cardiopulmonary resuscitation.
AB  - Pharmacist participation in cardiopulmonary resuscitation (CPR), including the
      basic life support (BLS) activities of artificial respiration and chest
      compressions, was studied. A questionnaire was mailed in September 1991 to the
      197 graduates (1986-90) of a Michigan college of pharmacy requiring BLS training
      for graduation. Another questionnaire was mailed in April 1992 to the 181
      pharmacy directors at all general acute-care hospitals in Michigan. The
      "graduate" survey covered practice setting, current status of BLS certification,
      use of BLS, and attitudes toward BLS training. The "director" survey covered the
      characteristics of the institution and its pharmacists, pharmacist involvement in
      CPR, and departmental BLS-training requirements. The response rates for the
      graduate and director surveys were 81% (160 questionnaires) and 76% (138),
      respectively. Only 66 (41%) of the graduates were currently certified in BLS, and
      only 77 (48%) had completed a BLS course since graduation. More than half (84, or
      53%) indicated they had never been involved in any CPR activity. Activities most
      likely to be reported were drug preparation, dosage calculation, documentation,
      and drug information; very few pharmacists had given artificial respiration or
      chest compressions. Forty-six (33%) of the directors indicated that pharmacists
      routinely were members of the CPR team. Most (59%) of these 46 hospitals did not
      require BLS training for pharmacists. Hospital size significantly affected
      whether pharmacists were included on the CPR team. Hospitals with decentralized
      pharmacists were more likely than hospitals with centralized pharmacists to have
      pharmacist involvement on the CPR team. Both study groups expressed ambivalence
      about the value of BLS training for their current pharmacy practice
      situations.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7641037
TI  - Self-reported memory of medication use by the elderly.
AB  - Correlates of self-reported memory for adherence to prescription drug regimens in
      noninstitutionalized elderly persons were studied. Independently living persons
      at least 55 years of age participated in a "brown-bag" medication review. A
      structured interview consisting of background questions and medication-related
      questions was conducted. Included in the interview were questions about general
      memory and questions about memory specifically related to medication use. Also
      asked were questions about demographic variables, the number of drugs being
      taken, the number of limitations on functional health and ability for self-care,
      the number of medical problems, and level of mental depression. A total of 105
      persons (mean +/- S.D. age, 81 +/- 9 years) were interviewed. Overall, the
      subjects rated themselves higher for medication-specific memory than for general
      memory. Global ratings of success in remembering to take medications as directed
      were moderately correlated (r = 0.44) with subjects' concerns about the
      seriousness of their general problems with memory. Level of depression was the
      best predictor (adjusted R2 = 0.18) of self-rated success in remembering to take
      medications. However, when the subjects were asked specifically about the
      frequency with which they "got off truck," age was the best predictor of problems
      (adjusted R2 = 0.14). Most of the subjects reported using strategies for
      remembering that were based on external cues, such as bedtime and meals. There
      was no association, though, between the presence or type of such a strategy and
      self-reported success in medication adherence. Most independently living elderly
      persons believed they were remembering to take their medications as directed and
      described strategies for doing so.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7641038
TI  - Pharmacist-operated drug information centers in the United States.
AB  - Pharmacist-operated drug information centers (DICs) in the United States were
      surveyed to obtain current information on the availability and scope of their
      services. Questionnaires were mailed in late 1991 to 179 institutions believed to
      have organized DICs. Topics covered in the questionnaire included staffing,
      resources, funding, and services provided. The results were compared with
      previous survey results to identify trends. Through 1992, 120 usable responses
      were received. Compared with findings from earlier surveys, DICs' affiliations
      with medical centers and hospitals have declined and affiliations with pharmacy
      schools have increased. More personnel work in DICs than ever. Computers are now
      used by nearly every DIC, there is an increased emphasis on quality-assurance
      programs for services rendered, and many DICs have increased revenue with new and
      expanded services. Although DICs are no longer increasing in number, their
      services are becoming more sophisticated.

PMID- 7641039
TI  - Compatibility of etomidate, thiopental sodium, and propofol injections with drugs
      commonly administered during induction of anesthesia.

PMID- 7641040
TI  - Stability of piperacillin sodium-tazobactam sodium in polypropylene syringes and
      polyvinyl chloride minibags.

PMID- 7641041
TI  - Widening effect of FTC investigation.

PMID- 7641042
TI  - Opinion polls rate refractive surgery preferences.

PMID- 7641043
TI  - Patient testimonials and radial keratotomy marketing--effective, but beware.

PMID- 7641044
TI  - Correction of high myopia with the Worst myopia claw intraocular lens.
AB  - BACKGROUND: Phakic anterior chamber lenses is one of the modalities used to
      correct high myopia. We report the initial results of our prospective study on
      the Worst myopia claw intraocular lens (IOL) that is fixated to the anterior
      iris. METHODS: We studied 35 eyes in 18 patients with a preoperative myopia
      ranging from -6.00 to -28.00 diopters (D). The follow up ranged from 6 months (n
      = 15) to 12 months (n = 20). RESULTS: In 26 (74.3%) eyes, the postoperative
      spherical equivalent refractive error was within 1.00 D of emmetropia. The mean
      refraction was stable between 1 to 2 months and 12 months. The mean spectacle
      corrected visual acuity improved from 20/50 to 20/40. The straylight measurements
      did not show a significant increase postoperatively (p = .64). The mean
      endothelial cell loss was 5.6% (range, +6.3% to -22.6%) at 6 months, and 8.9%
      (range, +0.77% to -23.5%) at 12 months. We did not encounter major complications.
      CONCLUSION: Implanting a Worst myopia claw IOL in high myopic eyes resulted in a
      stable, reasonably accurate refractive outcome. This group of patients will be
      followed longer because of concern over ocular complications with this technique.

PMID- 7641045
TI  - Digital system measurement of decentration of Worst-Fechner iris claw myopia
      intraocular lens.
AB  - BACKGROUND: Topography measures the centration in refractive and corneal
      refractive surgery, but until recently there was no effective method to measure
      decentration in intraocular lens (IOL) implantation. PATIENTS AND METHODS: We
      measured the decentration of 22 phakic eyes, in 14 high myopic patients, based
      upon photographs of the anterior segment using a digital analysis system
      (IMAGEnet Topcon Corporation 1988, Tokyo, Japan). These eyes had undergone IOL
      implantation for the correction of myopia with Worst-Fechner iris claw lenses.
      Decentration was measured with respect to the centers of both the cornea and
      pupil. RESULTS: Mean decentration of the IOL center from the cornea center was
      0.51 +/- 0.25 mm (range, 0 to 0.8374 mm). When measured with respect to the
      center of the pupil, the average decentration was 0.47 +/- 0.29 mm (range, 0.182
      to 0.9341 mm). A positive correlation between the decentration measurements of
      the two methods was found (p < .01 indicated statistical significance).
      CONCLUSIONS: This digital imaging system (IMAGEnet) accurately measured
      decentration of IOLs in myopic eyes.

PMID- 7641046
TI  - Excimer laser phototherapeutic keratectomy for shield ulcers and corneal plaques
      in vernal keratoconjunctivitis.
AB  - BACKGROUND: Shield-shaped corneal ulcers and corneal plaques in vernal
      keratoconjunctivitis are associated with delayed epithelial healing, as well as
      the risks of infectious keratitis and sterile stromal ulceration. Significant
      visual impairment due to scarring and irregular astigmatism may result from
      central corneal lesions. METHODS: Three eyes with central corneal lesions
      resulting from vernal keratoconjunctivitis were treated by excimer laser after
      active vernal keratoconjunctivitis was controlled and inflammatory plaque
      overlying the shield ulcers was removed. RESULTS: All three eyes showed rapid
      reepithelialization within 1 week. Spectacle-corrected visual acuity of 20/30 or
      better was obtained in each eye. CONCLUSIONS: In selected patients, excimer laser
      phototherapeutic keratectomy may be a useful adjunct in the treatment of shield
      shaped corneal ulcers and plaques in vernal keratoconjunctivitis.

PMID- 7641047
TI  - Comparison of laser and manual removal of corneal epithelium for photorefractive
      keratectomy.
AB  - BACKGROUND: Photorefractive keratectomy relies on precise ablation of cornea
      stromal tissue to achieve a desired change in refraction. The routine technique
      for photorefractive keratectomy has been manual debridement of the epithelium
      prior to performing excimer laser ablation. We investigated whether laser
      ablation versus manual debridement of the corneal epithelium influences the
      refractive result. METHODS: A retrospective matched controlled study analyzing
      the refractive outcome of 46 eyes after excimer laser photorefractive keratectomy
      was performed. Half of the eyes had the corneal epithelium ablated with the
      excimer laser, while the other half had mechanical removal. Topical postoperative
      corticosteroid dosing was different in the two groups. All photorefractive
      keratectomies were performed by the same surgeon (H.V.G.). The two groups were
      analyzed for statistical differences in refractive outcomes and corneal haze
      after 6 months. RESULTS: The mean preoperative spherical equivalent refraction in
      the laser removal group was -5.11 diopters (D), and -5.09 D in the manual group.
      At 6 months postoperatively, the mean spherical equivalent refraction in the
      laser group was +0.03 D and -0.40 D for the manual group (p = .21). At no point
      postoperatively was there any significant difference in the mean refractive
      outcome or variance of the refractive results between the two groups, although
      there was a trend toward greater correction with laser ablation of epithelium.
      There was no statistical difference in the amount of stromal haze by slit-lamp
      microscopy in the two different debridement groups. There was no significant
      difference in final uncorrected visual acuity, rate of reepithelialization, or
      reported incidence of halos or glare between the two groups. CONCLUSION: There
      was a tendency toward greater refractive correction at 6 months using the laser
      for corneal epithelial removal than manual debridement, although the difference
      was not statistically significant. The trend toward slightly higher correction
      emphasizes the need for care when removing epithelium with the laser to prevent
      concomitant stromal ablation.

PMID- 7641048
TI  - Randomized clinical trial of topical sodium hyaluronate after excimer laser
      photorefractive keratectomy.
AB  - BACKGROUND: Sodium hyaluronate (Healon) has been reported to promote corneal
      epithelial healing following severe eye burns in humans and rabbits. Endogenous
      hyaluronate has been shown to be significantly increased in the corneal tissue
      following extracapsular lens extraction, anterior segment trauma, and radial
      keratotomy. The authors report the use of topical sodium hyaluronate
      administration on the cornea of eyes which have been treated by photorefractive
      keratectomy for myopia. METHODS: Forty eyes of 40 patients undergoing excimer
      laser photorefractive keratectomy for myopia were studied to evaluate the effect
      of topical sodium hyaluronate versus placebo (Healon buffer) instillation on pain
      and corneal epithelial healing in an observer blind randomized clinical trial.
      RESULTS: There was no significant difference between patients whose eyes were
      treated with sodium hyaluronate and those treated with a placebo (Healon buffer),
      with regard to the amount of postoperative pain or the rapidity of corneal
      epithelial healing. CONCLUSIONS: Topical sodium hyaluronate administration showed
      no effect on pain or corneal epithelial healing following photorefractive
      keratectomy in this study.

PMID- 7641049
TI  - Comparison of yellow dye, continuous wave Nd:YAG, and argon green laser on
      experimentally induced corneal neovascularization.
AB  - BACKGROUND: Corneal neovascularization is generally undesirable because it can
      lead to corneal scarring, lipid deposits, and corneal graft failure. To eliminate
      these vessels, several techniques are available including laser photocoagulation.
      METHODS: This prospective study was designed to compare the effectiveness of
      three laser wavelengths (continuous wave Nd:YAG, 1064 nm; argon green 514 nm; and
      yellow dye, 570 nm) to obliterate experimentally induced corneal
      neovascularization in the rabbit. Corneal vascularization was created in 12
      rabbits by placing 7-0 silk sutures through two quadrants of the cornea. Once
      neovascularization was complete, the suture was removed and one of the three
      lasers was applied to occlude vessels at one of the neovascular sites. The other
      site was used as a control. RESULTS: The yellow wavelength, when compared with
      the green required fewer exposures to occlude corneal vessels. At no time during
      observation was any laser more effective than the control. In the continuous wave
      Nd:YAG group, tissue necrosis was needed to achieve closure of vessels.
      CONCLUSIONS: Yellow and green laser light are equally effective in eliminating
      the corneal vessels. Continuous wave Nd:YAG, as used here, appears to be a poor
      choice.

PMID- 7641050
TI  - Rapidly polymerized collagen gel as a smoothing agent in excimer laser
      photoablation.
AB  - BACKGROUND: Excimer laser photoablation effectively and precisely removes corneal
      tissue but may not smooth irregularities on the anterior corneal surface. An even
      surface might be obtained by applying a smoothing substance that fills in
      irregularities and ablates at the same rate as corneal tissue. Evaluation of
      collagen gel as a smoothing agent is reported. METHODS: Pure, type I collagen
      solutions were prepared to remain soluble at physiological pH and to
      spontaneously gel when exposed to cationic buffers. Collagen gels were formed on
      the surface of enucleated porcine corneas and on human donor corneas and exposed
      to varying pulses of 193-nanometer excimer laser energy. Effects of collagen gel
      on ablation depth, corneal surface smoothness, and smoothing of roughened cornea
      were evaluated by examining scanning electron micrographs of control and treated
      specimens. RESULTS: Collagen gels formed from 5 mg/ml collagen solutions
      dramatically altered the depth of photoablation. Photoablation of roughened
      cornea with collagen gels produced smooth corneal surfaces, whereas control eyes
      remained roughened and irregular. The smoothness of photoablated cornea surfaces
      improved when collagen gels were applied prior to photoablation. CONCLUSIONS: The
      rapidly gelling collagen solution appears to exhibit the functional properties
      required for an effective smoothing agent for excimer laser photoablation. The
      substance has low viscosity when applied to the corneal surface and forms a rigid
      gel when exposed to cationic buffer solution. In addition, the concentration of
      the collagen gel can be adjusted to provide different ablation rates.

PMID- 7641052
TI  - Sher receives third Troutman Award.

PMID- 7641051
TI  - New technique for knife and radial keratotomy.
AB  - BACKGROUND: Radial keratotomy is the most popular method of surgical correction
      of myopia, but requires further improvements. This study presents a new knife
      design for radial keratotomy. METHODS: Radial keratotomy was performed on 120
      eyes of 60 patients with myopia. We utilized two diamond knife designs. The new
      knife allows a surgeon to perform corneal incisions of varying programmed depth
      with one movement of the hand, deeper at the limbus. As a control, we used the
      standard Fyodorov knife. One eye was operated on with one type of knife, the
      other eye with the other type. The number of incisions was the same with both
      techniques. RESULTS: After a 2-year follow up of the group of eyes operated on
      with the new knife, the mean keratometric power changed from 43.20 diopters (D)
      to 39.30 D, and the mean amount of myopia from -4.37 to -0.32 D. In the group of
      eyes operated on with the standard knife, the mean keratometric power changed
      from 43.20 to 39.50 D, and the mean amount of myopia from -4.36 to -0.40 D.
      CONCLUSIONS: The final refractive effect of the new knife was equal to that of
      standard knives. However, the new knife was more convenient: duration of surgery
      was shorter, and there was no need to change the length of the blade to deepen
      the incisions during surgery.

PMID- 7641053
TI  - A sense of loss. Thoughts on the loss of babies 29 years on.

PMID- 7641054
TI  - A sense of loss. Miscarriage two years ago.

PMID- 7641056
TI  - RCM claims victory in pay dispute.

PMID- 7641055
TI  - Grief counselling following stillbirth.

PMID- 7641057
TI  - RCM/HVA conference "invest in breast together".

PMID- 7641058
TI  - Ethics & midwifery.

PMID- 7641059
TI  - Night duty isolation--difficulties in continuing education and communication.

PMID- 7641060
TI  - Different behavior of forearm blood flow during intermittent isometric handgrip
      in a thermo-neutral and a hot environment.
AB  - The purpose of the present study was to evaluate the different behavior of
      forearm blood flow (FBF) during intermittent isometric handgrip (IIHG, 6 seconds
      contraction +6 seconds relaxation) in a thermoneutral versus a hot environment.
      Six healthy men performed three times of 5-minute period IIHG at three different
      work loads (10%, 20% and 30% MVC). The IIHG was performed with the right hand.
      The experiments of IIHG were performed at two different air temperatures (25
      degrees C and 40 degrees C, RH: 50%), and an experiment without work was also
      carried out at 40 degrees C (RH: 50%). The physiological responses measured
      involved heart rate (HR), cardiac output (CO), mean arterial blood pressure
      (MBP), FBF, and skin blood flow (SBF). HR, CO and SBF showed higher values during
      IIHG at 40 degrees C than at 25 degrees C. MBP had a tendency to increase with
      the intensity of work load at both 25 degrees C and 40 degrees C. Since
      intramuscular pressure might increase during contraction periods at 20% MVC and
      30% MVC at 25 degrees C, FBF was significantly higher during relaxation periods
      than during contraction periods. FBF showed similar values between contraction
      and relaxation periods at 10% MVC at both temperatures. The present study
      suggested that FBF was sufficient for active muscles during IIHG at 10% MVC. FBF
      of contraction periods was close to that of relaxation periods at 40 degrees C
      due to the modulation of the sympathetic outflow to the muscles and/or the
      decreased efficiency of the muscle pump. It was suggested that FBF showed
      different behaviors during HHG at 25 degrees C versus at 40 degrees C.

PMID- 7641061
TI  - Thermophysiological effects of two different types of clothing under warm
      temperatures.
AB  - This paper is aimed to investigate which part of the body should be uncovered by
      clothing for the heat stress to be lessened under the influence of an ambient
      temperature increase from 32 degrees C to 40 degrees C. Two types of clothing
      were used as experimental garments: one was turtle necklined sports jacket with
      short sleeves and short pants (HALF) and the other was open round necklined
      sports jackets with long sleeves and short pants (OPEN). Both types of clothing
      were made of 100% vinyl. Uncovered area was same between HALF and OPEN. Five
      males volunteered as subjects. The subjects wearing either HALF or OPEN sat
      quietly in a bioclimatic chamber for 160 min, where ambient temperature (Ta) was
      gradually increased from 32 degrees C to 40 degrees C by 2 degrees C every 30 min
      with a relative humidity of 40%. Thermophysiological parameters such as
      esophageal temperature (Tes), tympanic temperature (Tty), local sweat rate, skin
      temperatures at 11 sites and evaporation were continuously measured. Main
      findings are as follows: 1) Tty was kept lower significantly in HALF than in OPEN
      during warm exposure. 2) An increase of local sweat rate was significantly lower
      in HALF. 3) Skin temperature at abdomen region was kept lower significantly in
      HALF, reflecting lower core temperature in HALF. It is concluded that HALF seems
      more beneficial than OPEN in reducing heat strain during warm exposure, due to
      more effective cooling by evaporation from the uncovered forearms (HALF) than
      from the uncovered upper trunk (OPEN).

PMID- 7641062
TI  - Effects of fructose ingestion on carbohydrate and lipid metabolism during
      prolonged exercise in distance runners.
AB  - The effects of ingestion of fructose (F), as well as of arginine (A) and citric
      acid (C) on both carbohydrate metabolism and lipid metabolism during prolonged
      exercise in seven distance runners on treadmill running were investigated by
      comparing it with those of glucose + arginine + citric acid (GAC) and placebo.
      With the values of the plasma glucose, though FAC as well as placebo
      contrastively indicated almost a flat distribution, GAC increased from 30 min
      rest before the exercise (i.e., the time for 500 ml intake of GAC) to the
      beginning of the exercise. The plasma glucose for GAC showed significantly higher
      values (138 +/- 22 mg/dl) than that for FAC or placebo, whose values were 102 +/-
      18 mg/dl and 93 +/- 8 mg/dl, respectively. The plasma glucose for GAC was likely
      to decrease gradually as the exercise progressed more. At the end of exercise,
      however, the plasma glucose for FAC indicated significantly higher values (100 +/
      12 mg/dl) than that for GAC, whose values were 89 +/- 12 mg/dl. Though the serum
      free fatty acid showed upward tendencies of values in all cases of FAC, placebo,
      and GAC as the exercise progressed, no significant difference of the values in
      those cases was observed (the following values were drawn at the end of the
      exercise; FAC:655 +/- 185 microEq/l, placebo:603 +/- 289 microEq/l, GAC:485 +/-
      140 microEq/l).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7641063
TI  - Use of B-mode ultrasound for visceral fat mass evaluation: comparisons with
      magnetic resonance imaging.
AB  - The validity of the visceral fat evaluation based on B-mode ultrasonography was
      tested on 30 healthy young women (mean age 19.6 years). The mass of visceral fat
      (VFM) was estimated by subtracting the subcutaneous fat mass (SFM) from the total
      body fat mass. The SFM was calculated as the sum of segmental subcutaneous fat
      mass determined from the surface area and mean thickness of adipose tissue in six
      body segments (face and neck, upper arm, forearm, thigh, lower leg, and trunk).
      Reproducibility of the determination of VFM by the repeated measures of SFM and
      total fat mass was sufficiently high with the difference of 5.0%. Serial cross
      sectional areas of visceral adipose tissue (VATarea) were measured by magnetic
      resonance imaging (MRI) at three different positions of the trunk (at umbilicus
      and at 3.5 cm upper and lower positions). The VFM correlated significantly to
      each VATarea (r = 0.75 to r = 0.78, P < 0.01). The present findings suggest that
      the VFM can be determined with the use of B-mode ultrasonography for the clinical
      assessment and field surveys.

PMID- 7641064
TI  - Sweat responses to pesticide-proof clothing influenced by textile materials.
AB  - Themoregulatory responses were compared at an ambient temperature of 30 degrees C
      and a relative humidity of 50% between two kinds of protective clothing for
      pesticide spraying. One was made of nylon with wet coating polyurethane (A) and
      another was made of cotton with water repellent finish (B). The clothing ensemble
      was composed of a short-sleeved cotton shirt, long cotton underpants, cotton
      socks, shoes and the protective clothing. Five young female adults served as
      subjects. They took a rest with protective clothing ensemble for 15 min and then
      walked on a motor-driven treadmill (80m/min, 5% uphill grade) for 40 min,
      followed by 20-min rest. The increase of forearm sweat rate was higher in
      clothing A than in clothing B in 4 out of 5 subjects, although the average values
      were not significantly different. The total sweat rate of the whole body was also
      significantly larger in clothing A. Mean skin temperature and local skin
      temperatures in the arm, the chest and the thigh were significantly higher in
      clothing A than in clothing B. Clothing microclimate humidity was significantly
      higher in clothing A, while clothing microclimate temperature tended to be higher
      in clothing A. Individual observations about thermal, humidity and comfort
      sensation disclosed that the sensation was improved as a whole in clothing B.
      Local sweat rate was linearly related to mean body temperature and the regression
      line for clothing A was located above that for clothing B in 4 out of 5
      subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7641065
TI  - Effects of upper limb exercise on thermoregulatory responses in patients with
      spinal cord injury.
AB  - We evaluated changes in body temperature, heart rate, and oxygen uptake during
      arm cranking exercise (20 watts, 30 min) in an artificial climate room at a
      temperature of about 25 degrees C or 35 degrees C (relative humidity, about 50%)
      in 5 patients with paraplegics due to spinal cord injury (SCI). The tympanic
      temperature (Tty) was significantly higher from rest to recovery at 35 degrees C
      than at 25 degrees C. The mean Tty after 10 minutes of rest was 36.68 degrees C
      +/- 0.396 (mean +/- SD) at a room temperature of 25 degrees C and 37.25 degrees C
      +/- 0.253 at 35 degrees C, showing a difference of about 0.5 degrees C. This
      difference was maintained during exercise and recovery. The Tty at the end of
      exercise was higher than that at the start of exercise by 0.66 degrees C +/-
      0.218 (mean +/- SD) at 25 degrees C and by 0.59 degrees C +/- 0.210 at 35 degrees
      C. The skin temperature (Tsk) in each measurement area (the head, arm, chest,
      thigh, shin, and calf) was significantly higher at 35 degrees C. Oxygen uptake
      did not differ between 25 degrees C and 35 degrees C. The heart rate was
      significantly higher at 35 degrees C than at 25 degrees C during rest and at the
      start of exercise but did not differ during exercise and recovery. Thus, mild
      moderate exercise in this study did not cause marked changes such as increases in
      body temperature and heart rate that affect biological function in SCI.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7641066
TI  - Kinetics of mixed venous CO2 pressure in constant-load exercise.

PMID- 7641067
TI  - Immunocytochemistry and in situ hybridization in the electron microscope:
      combined application in the study of virus-infected cells.
AB  - The present review evaluates methods for electron microscopic immunocytochemistry
      and in situ hybridization, using post-embedding techniques and colloidal gold as
      a label. Special emphasis is given to double labeling immunocytochemistry and
      double in situ hybridization and to their combined application on the same
      specimen. Brief guidelines are presented for fixation, embedding media, the use
      of polyclonal and monoclonal antibodies and nucleic acid probes. Conditions for
      labeling and binding of antibody and nucleic acid probes to the target and
      protocols for direct and indirect immunodetection are discussed. Combinations of
      direct and indirect immunodetections in multiple labeling experiments are
      summarized.

PMID- 7641068
TI  - Localization of immuno-analogues of erythrocyte protein 4.1 and spectrin in
      epidermis of psoriasis vulgaris.
AB  - The presence and localization of immuno-analogues of human erythrocyte protein
      4.1 and spectrin were examined in the epidermis of psoriasis vulgaris. Immunoblot
      analysis with antibodies against human erythrocyte protein 4.1 revealed that
      psoriatic epidermis contains a 4.1-like protein of 80 kDa, and also minor
      immunoreactive polypeptides, including a 45-kDa polypeptide. The 45-kDa band was
      not detected in non-lesional epidermis. Lesional epidermis of psoriasis contains
      spectrin-like proteins of 240 kDa. Analysis with immunofluorescence microscopy
      revealed that 4.1-like proteins were detected mainly in the cytoplasm of the
      suprabasal cells in lesional epidermis and in the peripheral cytoplasm of the
      basal cells in non-lesional epidermis. On the other hand, spectrin-like proteins
      were localized to the peripheral cytoplasm of basal keratinocytes in both
      lesional and non-lesional psoriatic epidermis. The present results indicate that
      proteins related to protein 4.1 and spectrin are consistently detected within
      epidermal cells of psoriasis, a chronic skin disease characterized by epidermal
      hyperplasia; the expression and distribution of protein 4.1 in lesional epidermis
      of psoriasis differs from that in non-lesional epidermis. These membrane skeletal
      proteins may be of significance in the hyperproliferative epidermis of psoriasis.

PMID- 7641069
TI  - Localization of deoxyribonuclease I gene transcripts and protein in rat tissues
      and its correlation with apoptotic cell elimination.
AB  - The expression and distribution of deoxyribonuclease I (DNase I) in rat parotid
      gland, kidney, small intestine and keratinized epithelium was further analysed at
      the level of its mRNA by in situ hybridization and correlated to
      immunohistochemical results using polyclonal anti-DNase I antibodies. High
      amounts of DNase I-specific mRNA and immunoreactivity were detected in the
      parotid gland, kidney and small intestine in agreement with previous
      immunohistochemical results. In the parotid gland, both the DNase I-specific mRNA
      and antigenicity were detected within the secretory cells. In the kidney, DNase I
      gene transcripts were localized in distal tubules and the collecting duct system.
      In this organ an identical localization of DNase I antigenicity was obtained. In
      the small intestine only the enterocytes covering the villi were shown to express
      DNase I-specific mRNA; the highest level being detected within the enterocytes
      along the lower third of the villi. In contrast, the highest level of
      immunoreactivity was found in enterocytes covering the middle and upper thirds of
      the villi. Within the stratified epithelium of the tongue, DNase I gene
      transcription and protein expression started in lower parts of the stratum
      spinosum and reached into the stratum granulosum. However, the gradient of DNase
      I gene transcript expression appeared to be shifted to lower layers of the
      stratum spinosum when compared to DNase I immunoreactivity.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7641070
TI  - L-NNA inhibits the histochemical NADPH-d reaction in rat spinal cord neurons.
AB  - In nerve tissue the histochemical nicotinamide adenine dinucleotide phosphate
      diaphorase (NADPH-d) reaction is considered a suitable marker for nitric oxide
      synthase (NOS) activity. We have previously shown that the NOS-specific inhibitor
      L-nitroarginine (L-NNA) can block NADPH-d staining in intermediolateral (IML)
      neurons of the rat spinal cord: such a reaction might serve as a control for the
      presence of a NOS-related catalytic activity, i.e., L-NNA-dependent NO synthesis
      in these neurons. However, L-NNA inhibition of neuronal NADPH-d is inconsistent
      and is therefore disputed by others. This prompted us to reinvestigate the
      reaction conditions to provide a standardized protocol for inhibition
      experiments. In IML neurons of formaldehyde-fixed spinal cord tissue, inhibition
      of NADPH-d reaction was tested by preincubation of frozen sections with the
      flavin-binder diphenylene iodonium chloride (DPI, 10 microM-1 mM) which blocked
      the NADPH-d reaction in a concentration-dependent way, suggesting an inverse
      relationship of inhibitor concentration and final reaction product generated.
      Preincubation with the NOS-specific inhibitor L-NNA in glycine-NaOH buffer (pH
      8.5-9.5) but not L-nitroarginine methyl ester (L-NAME) revealed a concentration
      dependent blocking effect on neuronal NADPH-d comparable to the effects seen with
      DPI, suggesting the existence of a L-NNA sensitive NADPH-d activity. Blocking
      with L-NNA (100 microM-10 mM) was prevented by excess L-arginine (10-100 mM),
      suggesting competitive binding sites. NADPH-d staining was not inhibited by 7
      nitro indazole, another NOS inhibitor. Thus, in formaldehyde-fixed nervous tissue
      both DPI and L-NNA inhibit the NOS-associated catalytic NADPH-d activity, thereby
      preventing NADPH-dependent conversion of nitroblue tetrazolium to formazan.

PMID- 7641071
TI  - Carbonic anhydrase isozyme VI in rat lacrimal gland.
AB  - Using monoclonal antibody specific to rat carbonic anhydrase isozyme VI (CA VI),
      the isozyme was localized in the lacrimal gland. A minority of acini (less than
      10% of the total) contained a few immunoreactive acinar cells. Enzyme
      histochemistry indicated that the CA VI-positive cells were the only cells
      possessing CA in the lacrimal acini. In the acinar cells, the reaction product
      for CA VI was distributed in the secretory granules and cytosol between secretory
      granules. Except for mitochondrial enzyme (CA V) activity, the intracellular
      distribution of enzyme activity was similar to that of CA VI immunoreactivity,
      suggesting that rat lacrimal acinar cells contain only CA VI and CA V. CA VI in
      the secretory granules was discharged into the acinar lumen and is considered to
      carry out its function on the surface of the conjunctiva and cornea. The
      cytosolic CA VI may function in situ and be involved in electrolyte and water
      secretion by the acinar cells. Polyclonal antibody to rat erythrocyte CA (CA I
      and CA II) stained only the interlobular ducts. In contrast, all the ductal
      elements exhibited CA enzyme activity. This discrepancy between
      immunohistochemistry and enzyme histochemistry suggests the presence of CA
      isozyme(s) other than CA I, CA II and CA VI in the lacrimal duct.

PMID- 7641072
TI  - A normal rabbit serum containing Golgi-specific autoantibodies identifies a novel
      74-kDa trans-Golgi resident protein.
AB  - A normal rabbit serum has been identified which contains Golgi-specific
      autoantibodies. In indirect immunofluorescence experiments the serum was found to
      stain the juxtanuclear Golgi complex in a variety of cell lines, including human
      skin fibroblasts, rat osteoblasts, rat myoblasts (L6), baby hamster kidney
      epithelial cells, and human embryonic kidney cells (293). Thus, the antigen(s)
      recognized by this serum seems to be well conserved and universally expressed in
      various mammalian cell types. Immunoelectron microscopy revealed that the epitope
      resides in the luminal side of the Golgi membranes, and that the antigen is
      concentrated in the trans-face of the Golgi stacks. In agreement with these
      results, brefeldin A treatment did not release the antigen from the membranes,
      but caused its redistribution partly into the endoplasmic reticulum but also into
      the juxtanuclear area, similarly as with other proteins known to be present in
      the trans-Golgi cisternae or trans-Golgi network. Our immunoprecipitation studies
      in human skin fibroblasts demonstrated that the serum recognizes specifically
      only a single protein with a molecular size of 74 kDa. This protein also
      cosedimented with a known trans-Golgi-specific marker protein,
      galactosyltransferase, after fractionation of subcellular organelles by Nycodenz
      gradient centrifugation. The widespread and polarized expression of this 74-kDa
      trans-Golgi resident protein suggests that it is required for the late Golgi
      functions in different mammalian cell types.

PMID- 7641073
TI  - Use of aminopropyltransferase inhibitors and of non-metabolizable analogs to
      study polyamine regulation and function.
AB  - The polyamines spermidine and spermine are essential for the growth of mammalian
      cells. This review describes the properties of the two aminopropyltransferases
      that are responsible for their biosynthesis, the synthesis and use of specific
      aminopropyltransferase inhibitors, and the use of analogs of the polyamines to
      investigate polyamine transport and function. Highly specific and potent
      multisubstrate adduct inhibitors of these enzymes have been synthesized while
      less potent inhibitors have been obtained by the synthesis of amines that bind at
      the active site. Studies with these inhibitors indicate that polyamines are
      needed for a normal rate of growth and that, although some of the functions of
      polyamines may be interchangeable, other functions may have a specific
      requirement for spermidine or spermine. Two groups of growth-promoting polyamine
      analogs can be distinguished: the many that are effective in short-term
      experiments compared to the few that can act over a prolonged period. The more
      stringent structural requirements for long-term growth are probably due to a need
      for spermidine, or a closely related analog, as a precursor of hypusine in the
      protein eIF-5A. Metabolically resistant polyamine analogs can be used as model
      substrates for studies of the polyamine transport system, which plays a critical
      role in maintaining normal cellular polyamine levels. The feedback regulation by
      high levels of polyamines that downregulates transport is essential to prevent
      the accumulation of polyamines at toxic levels. Such accumulation may be
      associated with apoptosis and, therefore, polyamine analogs are useful tools for
      investigating the mechanism(s) of polyamine-mediated toxicity.

PMID- 7641074
TI  - Biochemical effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related
      compounds on the central nervous system.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and related compounds are an important
      class of environmental contaminants which induce several types of biochemical
      alterations. Their effects have been most thoroughly characterized in the liver,
      especially regarding the Ah receptor-mediated induction of xenobiotic
      metabolizing enzymes. The behavioral signs exhibited by animals exposed to TCDD
      (progressive anorexia and body weight loss) suggest a role for the central
      nervous system (CNS) in TCDD toxicity. At lethal doses, TCDD affects the
      metabolism of serotonin, a neurotransmitter able to modulate food intake in the
      brain. This effect is associated with an elevated concentration of free
      tryptophan in the plasma. There does not appear to be any major changes in
      catecholaminergic neurotransmitter systems in TCDD-treated rats. Cytochrome P-450
      related enzyme activities are induced by TCDD in the brain. As is the case in the
      liver, this induction does not correlate with susceptibility to TCDD lethality in
      rats. The involvement of the CNS in TCDD toxicity is still obscure. Elucidation
      of this role as well as the mechanism of TCDD-induced wasting may well advance
      our understanding of the regulation of food intake and body weight.

PMID- 7641075
TI  - Role of lysine residues in the nucleotides binding to bovine liver high-Km
      aldehyde reductase.
AB  - The inactivation of bovine liver high-Km aldehyde reductase (ALR) by heat (47
      degrees C), 0.3 mM 2,4,6-trinitrobenzene sulfonate (TNBS) and 0.03 mM pyridoxal
      5'-phosphate (PAL-P) followed pseudo-first-order kinetic as a function of
      incubation-time and concentration of TNBS. Nucleotides which have a 2'-phosphate
      group, especially beta-NADPH and beta-NADP+, showed effective protection on ALR
      inactivation. However, typical substrates for ALR such as D,L-glyceraldehyde, D
      erythrose, D-glucuronate and p-carboxybenzaldehyde could not protect the enzyme
      from inactivation. Completely inactivated enzyme was estimated to have 2.07 TNBS
      modified lysine residues/mol enzyme from the determination of free amino group
      using fluorescamine (Ex = 390 nm, Em = 475 nm). Enzyme protected by beta-NADP+
      (96.5% remaining activity) did not lose a significant number of lysine residues.
      Kd-values for beta-NADPH and beta-NADP+ were estimated to be 0.48 microM and 4.7
      microM, respectively and TNBS-treated enzyme lost its ability to bind to these
      nucleotides.

PMID- 7641076
TI  - Domains in human interferon alpha-1 gene containing tandems of arginine codons
      AGG play the role of translational initiators in E. coli.
AB  - The AGG and AGA are the least used arginine codons in E. coli but they are the
      most preferable ones in eukaryotes. The low expression of some eucaryotic genes
      (such as human alpha-1 interferon gene) which contain clusters of AGG codons is
      explained either by the limited pool of the tRNA(AGG) (Varenne and Lazdunski,
      1986) or by the competition of these clusters with the Shine-Dalgarno (SD)
      sequence (Ivanov et al., 1992). The aim of the present study is to demonstrate
      the in vivo capacity of AGG tandems to bind to bacterial ribosomes. The two
      tandems of AGG codons (Arg12 Arg13 and Arg163 Arg164) of hIF alpha 1 with their
      surrounding nucleotides were cloned in a bacterial expression plasmid containing
      a strong promoter and a reporter gene (chloramphenicol acetyltransferase, CAT)
      devoid of a ribosome binding site. The results obtained showed that both AGG
      tandems initiated translation of the CAT mRNA with an efficiency equal to that of
      the consensus SD sequence and several fold higher than the native SD sequence of
      the CAT gene.

PMID- 7641077
TI  - Binding of etiopurpurin to human plasma proteins. Delivery in cremophor EL and
      dimethyl sulphoxide. III.
AB  - Binding of the photosensitizer etiopurpurin (ET2) to human plasma was assessed,
      using conditions that would yield a high percentage of ET2 in the form of LDL
      bound monomers which may favor photosensitizer tumor localization. Two delivery
      systems, Cremophor EL (CRM) and dimethyl sulphoxide (DMSO), were used. The
      binding of ET2 to CRM-modified lipoproteins was compared to the binding of the
      dye to the native proteins using delivery in DMSO. Plasma-bound monomers and
      unbound high density aggregates were shown to coexist. The density and rate of
      formation of the dye aggregates were correlated. The aggregates formed by
      delivery in DMSO could be partially converted into plasma-bound monomeric ET2.
      There was no mode-delivery-effect upon the distribution of monomeric ET2 among
      the plasma proteins. 70% of monomeric ET2 was bound to LDL and most of the
      remainder to HDL. In delivery in DMSO the yield of LDL-bound dye monomers (up to
      30% of added ET2) increased with decreasing concentration of ET2 in the delivery
      solution and with increasing time of incubation (< or = 48 hr). Long incubation
      also induced changes in the densities of LDL and HDL. The yields of LDL-bound
      monomers (up to 40%) increased with increasing concentration of CRM-bound ET2.
      High yields of LDL-bound monomers were obtained using both modes of delivery.
      Although the aggregates associated with the two modes of delivery had different
      properties. The change in lipoprotein composition might be involved in the
      conversion of aggregates into plasma-bound monomers.

PMID- 7641078
TI  - Ascorbate-induced free radical toxicity to isolated islet cells.
AB  - Ascorbate is known to be cytotoxic by generating free oxygen radicals, a property
      shared with the diabetogenic drug alloxan. Some reports indicate that also
      ascorbate may be diabetogenic. In this study the cytotoxicity of ascorbate on
      isolated mouse islet cells has been investigated. Ascorbate (0.5-2.0 mmol/l)
      induced a concentration-dependent increase of trypan blue uptake by the cells,
      indicating an increase of membrane permeability to the dye. Trypan blue uptake
      induced by 2.0 mmol/l ascorbate was inhibited by concomitant incubation of the
      cells with 200 mg/l superoxide dismutase, 200 mg/l catalase, 3.0 mmol/l
      cytochrome-c or 50 mumol diethylenetriaminepentacetic acid (DTPA), but not by 50
      mmol/l D-mannitol. The results indicate that ascorbate is cytotoxic to islet
      cells by metal-catalysed free radical generation.

PMID- 7641079
TI  - Effect of density-gradients on the binding of photosensitizing agents to plasma
      proteins.
AB  - The binding of photosensitizing agents to low-density lipoprotein is considered
      an important factor in tumor localization. We examined the affinity of a group of
      photosensitizers, varying in charge and hydrophobicity, for LDL, under conditions
      designed to determine whether the high salt concentration involved in
      conventional KBr gradients affected the results. Density-gradients containing KBr
      vs D2O were evaluated; the latter can delineate VLDL and LDL from other plasma
      components, while the KBr gradient readily resolved VLDL, LDL, HDL and albumin.
      Distribution of the photosensitizers to plasma fractions was assessed, along with
      the effect of Cremophor EL, an emulsifier used for formulation of water-insoluble
      drugs. Both the D2O and KBr gradients provided similar results with regard to the
      affinity of anionic, neutral or cationic photosensitizers for LDL. The use of
      Cremophor EL for drug formulation was associated with an altered electrophoretic
      lipoprotein profile. In some cases, affinity of CRM-solubilized sensitizers for
      plasma components varied with the density-gradient employed. The high salt
      concentration used in density-gradient fractionation had little effect on the
      affinity of photosensitizing agents to low-density lipoprotein but may introduce
      artifacts when emulsifiers are used in drug formulation.

PMID- 7641080
TI  - Nucleotide sequence of a cDNA coding for bovine mitochondrial aspartate
      aminotransferase.
AB  - Aspartate aminotransferase is a pyridoxal-phosphate dependent enzyme which plays
      a key role in cell metabolism. We describe the cloning and sequence analysis of
      the cDNA encoding bovine mitochondrial aspartate aminotransferase and compare the
      sequence with those of isoenzymes from other mammalian species. An adult bovine
      heart cDNA library constructed in lambda lambda gt11 was screened using two 32P
      end labeled synthetic oligonucleotides. From the screening of the cDNA library
      two positive clones were isolated. A subclone in pEMBL18, 6B2, generated from the
      longest recombinant phage was further analyzed. This clone contains an insert of
      2500 bp with an Open Reading Frame of 1287 bp that encodes a protein of 430 amino
      acids. The deduced amino acid sequence confirms previous results obtained by mass
      spectrometric sequencing. We calculated the percentage of amino acid identity for
      each protein pair and for each comparison the average number of amino acid
      substitution per site (Kaa); the lowest Kaa values were obtained from the
      comparison between the bovine and pig enzymes. This study shows that the rate of
      evolution of mammalian mitochondrial AspAT is lower and more constant than the
      equivalent cytosolic enzyme and adds to the growing body of knowledge on the
      evolution of the aspartate aminotransferase.

PMID- 7641081
TI  - Changes in the structure of pyruvate dehydrogenase complex induced by mono- and
      divalent ions.
AB  - The activity of pyruvate dehydrogenase complex purified from pig kidney cortex
      was affected by various mono- and di-valent ions and changes in ionic strength.
      The fluorescence emission spectrum of PDC exposed to 0.04 M ionic strength and
      excited at 280 nm exhibited a maximum at 334 nm; the fluorescence intensity of
      PDC appeared to depend upon the ionic strength and the K+ and Na+ content of the
      incubation buffer. Alteration of ionic strength to which the enzyme complex was
      exposed produced a change in the absorption of the complex at 230 nm. The
      presence of HPO4(2-) ions prevented changes in the UV absorption spectrum of PDC
      induced by the variation in ionic strength. The K+ and Na+ ions alone had no
      effect on the UV spectrum of PDC. Upon increasing the ionic strength to which the
      enzyme complex was exposed, dramatic changes in the circular dichroism (CD)
      pattern were observed. At 0.04 M ionic strength PDC exhibited a CD spectrum with
      minima at 216, 218 and 222 nm and a cross-over point at 215 nm. At 0.15 M ionic
      strength the CD spectrum of PDC exhibited minima at 223, 226, 228 nm and a cross
      over point at 221 nm. The presence of HPO4(2-) ions prevented alterations in the
      CD spectrum of PDC induced by variations in ionic strength. The K+ and Na+ ions
      had no effect on the CD spectrum of PDC.

PMID- 7641083
TI  - The ARRT of uremia therapy.

PMID- 7641082
TI  - Isolation and partial purification of mitochondrial and cytosolic rhodanese from
      liver of normal and p-dimethylaminoazobenzene treated mice.
AB  - Rhodanese (thiosulfate:cyanide sulfurtransferase, E.C. 2.8.1.1), an enzyme
      involved in heme regulation, showed distinctive mitochondrial and cytoplasmic
      activities in several models of tumorigenesis. To investigate the basis for these
      differences, the enzyme was partly purified and characterized from the
      mitochondrial and cytosolic liver fraction of mice treated with the carcinogen p
      dimethyl-aminoazobenzene (DAB). A linear relationship between incubation time and
      specific activity was observed up to about 30 min for cytosolic enzyme and 15 min
      for mitochondrial enzyme irrespective of whether or not the enzyme was derived
      from treated or untreated animals. The optimum incubation temperature was 3
      degrees C for the enzyme of both fractions in control animals and 30 degrees C
      for treated animals in both cases. In control and DAB treated animals the
      cytoplasmic rhodanese exhibited a maximum at a lower pH than for the
      mitochondrial enzyme. The enzyme showed typical Michaelis-Menten behavior with
      cyanide inhibition at concentrations higher than 25 mM for controls and 10 mM for
      treated animals for both fractions and thiosulfate inhibition at concentrations
      higher than 100 mM in all cases studied. Km values of 190 and 65.66 mM were
      obtained for thiosulfate and 6.37 and 9.79 mM for cyanide for both mitochondrial
      and cytosolic fractions of control animals; while Km values of 31.75 and 4.58 mM
      were obtained for thiosulfate and 0.61 and 1.11 mM for cyanide in both fractions
      of treated animals. We demonstrated differences in the kinetics for rhodanese
      derived from mitochondrial and cytoplasmic fractions of livers taken from tumor
      bearing mice. These differences might provide an explanation for the
      abnormalities of heme synthesis previously reported during hepatocarcinogenesis.

PMID- 7641084
TI  - Assessment of adequacy in peritoneal dialysis.
AB  - Adequacy of peritoneal dialysis has been less well studied than that of
      hemodialysis. Fractional urea removal, total creatinine removal, and various
      indices have been proposed to reflect or predict patient morbidity and mortality.
      No prospective study has been published in this regard. To evaluate this area
      further, in addition to reviewing selected literature, 45 continuous ambulatory
      peritoneal dialysis (CAPD) patients were recruited in two dialysis centers for a
      prospective study on treatment adequacy. Patients were well rehabilitated and had
      no peritonitis or hospitalization in the 6 months before the study. Urea and
      creatinine kinetics were analyzed, as were dietary intake and fluid balance. The
      weekly Kt/V, calculated to include peritoneal and residual renal clearance
      (KprT/V), averaged 1.77 with a Kt/V hemodialysis equivalent of 0.59. Patients
      with residual renal function (58% of the studied population) had an average
      residual renal clearance of 3.42 mL/min, and had lower steady-state
      concentrations of urea nitrogen and creatinine in the plasma than patients with
      no residual renal function. As a consequence, a lower percent excretion of urea
      and creatinine in the peritoneal fluid was observed in the former patients
      compared with the latter, where the peritoneal route was the only one for solute
      excretion. The concentration profiles in blood appear to be the critical factor
      in achieving the final target of the treatment, ie, the excretion of the overall
      amount of waste products derived from protein and other metabolic pathways. The
      constant blood levels in CAPD explain why such a low Kt/V can be adequate
      whereas, in hemodialysis, a higher Kt/V is required.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7641085
TI  - Financing of end-stage renal disease care: past, present, and future.
AB  - The Medicare end-stage renal disease (ESRD) program has offered financial access
      to needed health care for ESRD patients, and it has given ESRD providers a
      reliable source of payment for their services. Total Medicare ESRD expenditures
      have increased since the inception of the program, due mainly to increased
      enrollment and changing patient mix. As a result, cost control is a dominant
      theme of payment policy. This article describes the history of Medicare ESRD
      financing policy and identifies related service delivery issues including
      treatment technology, service resources, treatment processes, and patient
      selection. It also discusses several options available to Medicare for managing
      the growth of ESRD program costs, including capitation payment methods, control
      of ESRD enrollment, and payment for erythropoietin treatment. Possible future
      changes in financing ESRD are identified. With a goal to control costs. Medicare
      probably will use payment methods to change service mix and reduce use by
      influencing provider incentives and marketplace competition. Health system reform
      also may affect ESRD benefits and payments, if the ESRD program is folded into a
      new financing system. ESRD patients and providers face a challenge of uncertainty
      during this period of change.

PMID- 7641086
TI  - Developments and dilemmas in renal transplantation.
AB  - The number of patients waiting for a kidney transplant is about three times
      greater than the number of transplants performed each year. This article
      highlights current immunosuppression protocols and the newer immunosuppressive
      drugs under investigation in a number of multicenter trials. These hold out the
      promise of reducing the frequency of acute rejection and of prolonging graft
      survival. They are divided into three groups. The first, like cyclosporine,
      interferes with the action of interleukin 2. The second, like azathioprine, are
      antimetabolites; and the third, new monoclonal antibodies. The use of antibody
      induction therapy is compared with standard regimens. There are risks related to
      prednisone withdrawal protocols and inadequate cyclosporine dosing that may lead
      to accelerated graft loss. Cardiovascular disease is a significant problem in
      older diabetic patients for whom coronary angiography is recommended. A defined
      set of risk factors is outlined that predicts which younger diabetic patients
      should have a cardiovascular evaluation. Chronic liver disease is a growing
      problem and rational strategies are emerging from studies of patients with biopsy
      proven active hepatitis. The presence of hepatic inflammation is associated with
      progressive liver disease and patients must be made aware of this risk when
      seeking transplantation. A large number of studies of various prophylactic
      regimens are starting to provide data on the cost-effective reduction of
      cytomegalovirus disease in transplant recipients. It is recommended that patients
      receiving antibody therapy also receive preemptive gangciclovir. The issue of
      chronic allograft rejection is discussed briefly. The most important predictors
      of chronic allograft rejection are the frequency of acute rejection, inadequate
      immunosuppression, and infections.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7641087
TI  - Cognitive, psychosocial, and physical development in infants and children with
      end-stage renal disease.
AB  - The purpose of this article is to synthesize research related to the cognitive,
      physical, and psychosocial development of children with end-stage renal disease
      who are receiving conservative management, hemodialysis or peritoneal dialysis,
      or who have received transplants. An impressive array of research in these three
      areas of development was found, but more work is needed. Suggestions are made for
      more multicenter research with larger sample sizes and greater generalizability.
      In addition, more developmental research that includes measures of renal disease,
      such as age at onset, severity of disease, and length of time in renal failure,
      is needed.

PMID- 7641088
TI  - Urea kinetic modeling at high urea clearances: implications for clinical
      practice.
AB  - The original description of urea kinetic modeling in hemodialysis was based on a
      single pool of fluid equal to total body water. This assumption is valid only if
      the rate of transport between compartments is sufficiently rapid compared with
      the rate of urea removed by hemodialysis. We have reexamined the issue of urea
      compartmentation using 10 patients with initial BUN values ranging from 28 to 101
      mg/dL who were studied while on high flux hemodiafiltration. Sampling was carried
      out at times as short as 1 minute after the beginning of the treatment. In 4
      patients, samples were also drawn after the dialysis ended. The measured BUN
      values were used to fit a two-compartment, variable-volume kinetic model. The
      mean urea diffusive clearance of the dialyzer during the treatment was 503
      mL/minute, and the bidirectional urea clearance between compartments was 1,282
      mL/minute. The percentage of total body water in the rapidly exchangeable
      compartment was 35.4%. Comparison with a one-compartment, variable-volume model
      showed a statistically better fit for all patients with the more complex model.
      In the 4 patients studied in the postdialysis period, the rebound in BUN ranged
      from 22% to 24%. These studies show that, at high urea clearances, the urea
      distribution space and, therefore, dialysis modeling requires two compartments.
      These results explain the majority of the rebound in urea concentration observed
      30 to 60 minutes following the discontinuation of the dialysis treatment and
      point out an improved strategy for monitoring the efficiency of the treatment
      delivered to the patient.

PMID- 7641089
TI  - The impact of recombinant human erythropoietin on exercise capacity in
      hemodialysis patients.
AB  - Peak oxygen uptake (VO2peak) of patients with end-stage renal failure treated
      with hemodialysis is very low. The improvement of anemia with recombinant human
      erythropoietin (rHuEPO) results in a very small change in VO2peak. This change is
      minimal compared with the magnitude of change in hematocrit, suggesting that
      other factors continue to limit exercise tolerance. This article reviews the
      physiology of oxygen transport and the determinants of VO2peak. Anemic
      hemodialysis patients are limited by a reduced cardiac output response to
      exercise and an inability to widen the arterio-venous oxygen difference. The lack
      of change in cardiac output and a remaining low arterio-venous oxygen difference
      following improvement of anemia with rHuEPO therapy suggest an underlying muscle
      limitation to exercise. Evidence for this muscle limitation is presented.
      Exercise training may improve the ability of muscle to use oxygen, thus
      optimizing the effect of the increased hematocrit resulting from rHuEPO therapy.

PMID- 7641090
TI  - Renal replacement therapy in diabetic nephropathy.
AB  - The case of a patient with diabetes mellitus and renal failure is presented and
      discussed. This case represents the very successful course of a diabetic patient
      who received peritoneal dialysis for 14 years. Not all patients with end-stage
      renal disease (ESRD) from diabetic nephropathy are this fortunate. The success
      and complications of dialytic modalities are discussed by a nephrologist and
      nurse dialysis coordinator. Renal transplantation, the preferred treatment for
      most diabetic ESRD patients, is discussed by a nurse transplant coordinator.
      Simultaneous pancreas kidney transplantation, with its potential benefits in the
      future is discussed by an experienced transplant surgeon. In addition, the
      psychosocial issues of renal failure, dialysis, and transplantation in the
      diabetic patient are addressed by clinical social workers. Lastly, the very
      important issue of foot care and treatment, and prevention of vascular-related
      morbidity is discussed by a practicing podiatrist. With such a multidisciplinary
      approach, medical and psychosocial outcomes can be optimized for diabetic
      patients with renal failure.

PMID- 7641091
TI  - Hemodialysis membrane biocompatibility in acute renal failure.
AB  - Hemodialysis is a lifesaving procedure for patients with acute renal failure.
      Nevertheless, the institution of hemodialysis may result in a continued or
      accelerated decline in renal function. Loss of osmotic drive and hypotension may
      be partially responsible for this observation. However, multiple lines of
      evidence suggest that the nature of the hemodialysis membrane also influences
      renal function following acute renal failure. The cellulosic hemodialysis
      membrane activates humoral pathways and the cellular elements of blood. The
      inflammatory responses entrained from the activation result in hypersensitivity
      reactions attributable to anaphylatoxin generation, hypoxemia, increased
      susceptibility to infection, and catabolic events. In addition, recent studies
      indicate that the use of bioincompatible membranes delays recovery from acute
      renal failure. Increased numbers of neutrophils are found in the glomeruli
      following exposure to cellulosic membranes, suggesting that inflammatory events
      induced by complement activation may mediate continuing renal injury and
      prolonged recovery from acute renal failure. Membrane choice for patients with
      acute renal failure is emerging as an important therapeutic consideration, just
      as it is for those patients on long-term dialysis.

PMID- 7641092
TI  - Blood flow measurement during hemodialysis.

PMID- 7641093
TI  - The latest trend in patient care: self service.

PMID- 7641094
TI  - Building RN political activism for a challenging future.

PMID- 7641095
TI  - RNs and health care workers unite to battle patient care crisis.

PMID- 7641097
TI  - Title 22 hearings: RNs urge DHS to protect patients.

PMID- 7641096
TI  - Most frequently asked questions about the effects of restructuring.

PMID- 7641098
TI  - Professional crisis of a lifetime sparks united vision of care.

PMID- 7641099
TI  - The nursing process & caregivers' roles.

PMID- 7641100
TI  - Surgical complications of the Le Fort I osteotomy--a retrospective review of 146
      cases.
AB  - A retrospective review of 146 cases with Le Fort I osteotomy performed between
      1981 and 1990 is presented. A complication of 6.1% was recorded. These
      complications include intraoperative hemorrhage, trigeminal nerve injury,
      oronasal fistula and dental injury. Although the Le Fort I osteotomy has proven
      to be relatively safe, improvements in technique will further reduce the
      incidence and the severity of complications.

PMID- 7641101
TI  - Parameters of semen analysis affecting the pregnancy rate of artificial
      insemination with husband's spermatozoa.
AB  - The efficacy of intrauterine insemination with husband's semen (AIH) is well
      established for some types of infertility. Results that had been reported
      previously were Dwing difficult to assess owing to the low number of patients or
      treatment cycles as well as an inadequate definition of the indications in most
      cases. In this study, we report our experience with intrauterine insemination
      (IUI) using post-treated sperm suspension from husband's semen in the treatment
      of infertility. A total of 328 treatment cycles were completed from January to
      December in 1991. The indications for AIH/IUI were male infertility (130 cycles),
      unexplained infertility (87 cycles), sex selection (72 cycles) and anovulatory
      disorder (39 cycles). Sixty-eight pregnancies were achieved. The clinical
      usefulness of AIH/IUI with or without concomitant hMG regimens were established
      according to diagnostic subgroups. In our results, the cycle fecundity of
      pregnancy was higher in patients with ovulatory disturbance. The importance of
      sperm motility confirmed by our results that have compared by the serial sperm
      parameters. The motile sperm count may appear to be a highly consistent parameter
      that serves as a sensitive indicator of sperm function and correlation of
      successful pregnancy in our results. In conclusion, this study indicates that AIH
      with controlled ovarian hyperstimulation can result in higher viable pregnancy
      rate, and it is also a non-invasive and relatively easy procedure. We believe
      that this is a transient useful method for the treatment of non-organic
      infertility, prior to any attempt of aggressive assisted reproductive procedures.

PMID- 7641102
TI  - Pollakiuria: extraordinary daytime urinary frequency a common problem in
      pediatric practice.
AB  - Forty-eight children (28 males and 20 females) with acute onset of isolated
      daytime urinary frequency were retrospectively reviewed. Their age at the onset
      of symptom ranged from 4 to 7.8 years (median 6.3 years). Clinical evaluations by
      noninvasive means are completely normal in all patients. Treatment with
      anticholinergics or antibiotics did not relieve the symptom. In all patients,
      urinary frequency was resolved spontaneously after an average of 1.8 months from
      time of onset. There was no particular relationship between the season and the
      occurrence of the symptoms. Although the actual cause of pollakiuria is still not
      known, some kinds of psychophysiologic reaction has been implicated. In only 19
      out of 48 patients, the possible trigger factor could be obtained. It should be
      emphasized that this clinical entity is a benign, self-limited situation that
      requires no invasive investigation or management other than reassurance.

PMID- 7641103
TI  - Electrocardiographic findings of organophosphate intoxication in emergency
      department as predictors of prognosis: a retrospective analysis.
AB  - To investigate the clinical significance of electrocardiographic (ECG) findings
      in patients with organophosphate intoxication and to find predictors for
      prognosis, we reviewed 170 patients whose ECG was taken in the emergency
      department (ED) from 1981 to 1989. There were 67 cases whose ECG showed
      prolongation of corrected Q-T interval (QTc). In this group, the mortality rate,
      respiratory failure rate and frequency of ventricular premature contraction (VPC)
      were significantly higher than those of patients without QTc prolongation. In the
      group with presence of VPC, the overall mortality rate and respiratory failure
      rate were also significantly higher when compared with those without VPC. We
      concluded that QTc prolongation and the presence of VPCs in patients with
      organophosphate intoxication may predict their clinical respiratory failure and
      mortality.

PMID- 7641104
TI  - The quantitative measurements of hip isometric muscle torques in Chinese young
      adults--a preliminary report.
AB  - A standard procedure for measurement of hip muscle strength (maximal isometric
      torque) with the Cybex 340 isokinetic dynamometer is presented. Twenty-two
      healthy males aged 30-40 years (average 34.3 years) were tested on hip flexors,
      extensors and abductors; in which the factors as sex, age, dominant side and
      testing session were all eliminated. The test was redone two weeks later on the
      same 10 males to evaluate its reproducibility. The results disclosed the maximal
      isometric torque of the hip flexors was stronger than that of extensors and
      abductors in both sides hips. The comparison between two sides hips showed only
      the abductors of right side hip significantly stronger than that of left side (P
      = 0.0259). The tests between the two different periods were quite compatible. The
      results have clinical implications for objective assessment of preoperative and
      postoperative hip strengths in patients with hip arthropathy and thus giving a
      reasonable guidance for physiotherapeutic management.

PMID- 7641105
TI  - Clinical application of simultaneous pattern VEP and pattern ERG recording.
AB  - Thirteen eyes of optic neuropathy and 13 eyes of maculopathy during Sep. 1990-May
      1992 were studied by simultaneous pattern VEP (PVEP) and pattern ERG (PERG)
      recording. In optic neuropathy, the P100 of PVEP was delayed in 7 eyes (ave.
      108.87 msec; normal 94.41 +/- 3.51 msec), absent in 5 eyes, normal in 1 eye.
      Their PERG showed normal P50 amplitude (either normal or delayed latency) but
      small or absent N95 in 8 eyes. In maculopathy, the P100 of PVEP was delayed in 2
      eyes (ave. 103.59msec), absent in 7 eyes, normal in 4 eyes. However, their PERG
      showed 12 eyes had small or absent P50. Combined PVEP & PERG test, when compared
      to PVEP alone, increased the diagnostic value from 57.1% to 100% for optic
      neuropathy and from 42.9% to 80% for maculopathy in this study. Thus,
      simultaneous PVEP & PERG recording is highly recommended in evaluation of
      anterior visual pathway disorders.

PMID- 7641106
TI  - Transtympanic microendoscopy of the eustachian tube: a new approach method.
AB  - The eustachian tubes (ET) of sixteen patients suffering from chronic otitis media
      or otitis media with effusion were observed transtympanically by using an 0.85mm
      tip-controllable fiberoptic microendoscope. The examination was accomplished
      under local anesthesia. The osseous portion of ET was endoscopically accessible
      and was usually found patent in most patients. Similar to findings of the
      cadaveric temporal bone studies, a collapsed wall was observed in the lumen of
      isthmus and valve section of cartilaginous ET. The parapharyngeal section of
      cartilaginous ET, however, was found to include an open lumen, where pulsatile
      movements of the medioinferior membranous ET wall could be seen. In addition,
      special endoscopic findings of the ET lumen in different patients including
      relatively narrow isthmus, mucus accumulation, edematous mucosa, intraluminal
      tumor invasion, opening failure of valve section, etc. were also observed.
      Despite the technical difficulties involved, transtympanic ET microendoscopy is a
      potentially useful technique for exploring the physiology and pathophysiology of
      ET.

PMID- 7641107
TI  - [Postoperative evaluation in mandibular prognathism treated by bilateral sagittal
      split osteotomy].
AB  - The present study was undertaken to evaluate the postoperative relapse from the
      period of unwiring to 1 year postoperatively and its correlation to the amount of
      mandibular setback and change in vertical dimension after mandibular bilateral
      sagittal split osteotomy. Twenty-seven patients were evaluated cephalometrically
      by the time preoperatively, 6 weeks, 6 months and 1 year postoperatively. It was
      found that 1) the average amount of mandibular setback at pogonion point, 6 weeks
      postoperatively, is 7.6mm backward and 1.9mm downward, 2) the average amount of
      horizontal relapse at pogonion point, 6 months and 1 year postoperatively, are
      1.9mm and 2.3mm respectively. 86% of the horizontal relapse, 1 year
      postoperatively, occurs in the first 6 months after removal of intermaxillary
      fixation, 3) the average amount of vertical relapse at pogonion point, 6 months
      and 1 year postoperatively, are 0.9mm and 1.1mm upward. 82% of the vertical
      relapse, 1 year postoperatively, occurs in the first 6 months after removal of
      intermaxillary fixation, 4) the amount of 1 year postoperatively horizontal
      relapse is significantly correlated both with the amount of horizontal mandibular
      set back and vertical downward change (r = 0.58, 0.67, p < 0.001), whereas the
      amount of vertical relapse is with the vertical downward change only, but
      horizontal setback isn't.

PMID- 7641108
TI  - [Diagnosis of intraperitoneal injuries in patients with pelvic fractures].
AB  - It is difficult to diagnose blunt abdominal trauma in unstable patients with
      pelvic fractures. In the United States the standard diagnostic procedures for
      these patients were the physical examinations and diagnostic peritoneal lavages.
      However, abdominal echograms were prevalent in Europe and Japan. We reviewed 60
      patients suspected blunt abdominal trauma in 804 pelvic fractures in the past
      four years. Eighteen DPLs and twenty-five abdominal echograms were done
      separately. Sensitivity, specificity, and accuracy were 100%, 40%, 66% for DPL
      and 94.7%, 50%, 84% for abdominal echograms respectively. Besides the better
      correlation with the results for echogram, it provides easy availability,
      noninvasiveness, and imaging function. Thus we recommend that the echogram be the
      first-line screening test DPL acts as a complementary test, especially in the
      cases of bowel perforation.

PMID- 7641109
TI  - Plasmacytoid lymphocytic lymphoma presenting with IgG hyperviscosity syndrome and
      peritoneal lymphomatosis.
AB  - We reported a 74-year-old woman with plasmacytoid lymphocytic lymphoma who
      initially presented with exertional dyspnea, conscious disturbance, ascites, and
      lytic skull lesions. Protein electrophoresis and immunoelectrophoresis showed
      monoclonal IgG-lambda gammopathy with IgG level of 13300 mg/dl and marked
      suppression of the residual normal immunoglobulins. Abdominal computed tomography
      (CT) revealed a pattern mimicked cancerous peritonitis. She responded to
      plasmapheresis with much clinical improvement of the hyperviscosity syndrome but
      died of H. influenza sepsis 3 weeks after diagnosis. The unusual and interesting
      features of this case included: (1) IgG hyperviscosity syndrome and diffuse
      peritoneal involvement as the initial manifestations in plasmacytoid lymphocytic
      lymphoma, and (2) presence of lytic bone lesions in conjunction with high level
      of M--component and marked suppression of normal residual immunoglobulins in a
      patient with lymphoma rather than multiple myeloma.

PMID- 7641110
TI  - Splenic artery aneurysm rupture in pregnancy--a review and case report.
AB  - Spontaneous rupture of a splenic artery aneurysm in the third trimester of
      pregnancy is a catastrophic event associated with a very high fetal and maternal
      mortality rate. Review of the literature reveals nine reported cases of combined
      maternal and fetus survival. None were diagnosed prior to rupture and the need
      for an emergency laparotomy. They survived due to early surgery after fetal
      distress was noted. We present a 29-year-old female presenting at 33 weeks
      gestation seeking emergency assistance for vomiting, diarrhea and epigastralgia.
      During her evaluation and initial management she into shock. At laparotomy a
      ruptured splenic artery aneurysm was found and ligated. After splenectomy the
      mother recovered well but unfortunately fetus did not survive.

PMID- 7641112
TI  - Granulosa cell tumor and dermoid cyst--report of one case.
AB  - Granulosa cell tumor combined with dermoid cyst in the same ovary is extremely
      rare. This report describes such a case in a 55-year-old postmenopausal woman
      presenting with left lower abdominal pain. The resected fist-sized left ovary
      disclosed a dermoid cyst containing a mural nodule which was found to be a
      sarcomatoid granulosa cell tumor histologically. She has been disease free for
      two years after the operation.

PMID- 7641111
TI  - Salmonella psoas abscess--a case report.
AB  - The clinical presentation of psoas abscess is often non-specific and insidious
      that may mislead the diagnosis and treatment. The abscess often extends beyond
      the retroperitoneum and pelvis before its diagnosis, and leads to serious
      complications. Many diseases have the similar signs and symptoms and must be
      ruled out. Computed tomogram is the most useful and reliable diagnostic tool.
      Only a few cases of salmonella psoas abscess were reported in the literature, and
      were usually associated with spinal osteomyelitis or septic hip. We present a
      case of salmonella psoas abscess in a patient with diabetes mellitus. The patient
      had the history of cholecystitis with sepsis due to salmonella infection 4 years
      before and cholecystectomy had been done. No associated lesion was found to be
      associated with the abscess, and we believed the abscess being the result of
      recurrent bacteremic attack. High index of suspicion, early diagnosis, adequate
      drainage and effective antibiotic treatment are the key points in managing the
      disease.

PMID- 7641113
TI  - Pulmonary echinococcosis--a case report.
AB  - Pulmonary echinococcosis is a rare disease in Taiwan and has never been reported
      in Taiwan's literatures. Here we report an overseas Chinese from Calcutta, India,
      presenting with recurrent hemoptysis and chest pain and with two big lung masses
      on chest roentgenogram. Rupture and spike fever ensured after fine needle
      aspiration of the cysts. Successful surgical intervention was obtained and
      echinococcal infection was documented pathologically.

PMID- 7641114
TI  - Fabellar impingement after total knee replacement--a case report.
AB  - An unusual postoperative knee pain caused by fabellar impingement after total
      knee replacement is described. A 68-year-old woman with knee arthrosis had large
      fabellae in both knees. She had total knee replacements of both knees. One knee
      developed fabellar impingement to the knee prosthesis, while the other knee was
      free of symptoms due to simultaneous fabellectomy during knee replacement. At 3
      month postoperative follow-up, pain and local tenderness at posterolateral aspect
      of the left knee was noted during flexion up to 90 degrees. Physical examination
      revealed a tender fabella on the posterolateral part of the left knee. The
      lateral radiograph of the knee revealed a large fabella impinging on the
      prosthesis. The symptoms and signs were alleviated after surgical excision of the
      fabella. Careful evaluation of the preoperative lateral radiograph of the knee is
      necessary to detect a large fabella. If it is present and larger than 1 cm,
      excision during knee replacement is recommended.

PMID- 7641115
TI  - [Small cell lung cancer with liver and bone metastasis associated with
      hypercalcemia and acute pancreatitis--a case report].
AB  - A 67-year-old man was hospitalized with the chief complaint of diffuse abdominal
      pain for 3 days. Hypercalcemia and acute pancreatitis was found by laboratory
      examination. Abdominal CT scans showed swelling of the pancreas, multiple liver
      tumors and osteolytic lesions of bone. Upper mediastinal lobulated mass was
      suspected from chest x-ray examination, then small cell lung cancer (SCLC) was
      proved by bronchoscopic and pathological examination. The final diagnosis is SCLC
      with liver and bone metastasis associated with hypercalcemia and acute
      pancreatitis. After pancreatitis subsided, the patient was put on chemotherapy.
      Unfortunately, due to immunocompromise, he died of pneumonia and sepsis. There
      was no reasonable explanation regarding to the cause of acute pancreatitis except
      hypercalcemia, which might be due to SCLC with bone metastasis. This is the first
      report of such a complication in a patient with SCLC.

PMID- 7641116
TI  - [Play therapy for a child with separation anxiety disorder].
AB  - Separation anxiety disorder is characterized by severe and exceeding anxiety and
      fear when a child is facing separation with attachment objects. More over, it
      affected the child in language, emotional and social interest and development.
      These children usually brought to physician's attention due to refusal to go to
      school, social withdraw or multiple somatic complaints with attachment behavior
      wanted to be nearby or closed to the attachment objects. A child's early
      attachment relationship and previous separation experience play a major role in
      the formation of separation anxiety disorder. This report presents a
      psychoanalytically-oriented play therapy for a 2-year-8-month-old boy in 17
      months period total of 54 sessions. According to the main themes in each session
      the process can be divided into 4 stages, namely establishing therapeutic
      relationship, expressing repressed emotions, management of transference,
      attachment and conflict in therapy, and self growth and termination. The
      formulation of this case and management were discussed.

PMID- 7641117
TI  - [Non-significant in univariate but significant in multivariate analysis: a
      discussion with examples].
AB  - Perhaps as a result of higher research standard and advancement in computer
      technology, the amount and level of statistical analysis required by medical
      journals become more and more demanding. It is now realized by researchers that
      univariate analysis alone may not be sufficient, especially for complex data
      sets. Additional, and sometimes even contradictory, results may be found using
      multivariate analysis. During the course of data analysis, a common practice is
      to include in multivariate analysis only those variables that are statistically
      significant in univariate analysis. Such a habit is risky as some variables not
      significant in univariate analysis may become significant in multivariate
      analysis. In this study, we identify, with examples, four possible scenarios in
      which the above situation could occur: (1) the effect of unbalanced sample size;
      (2) the influence of missing data; (3) an extremely large within group variation,
      relative to between group variation; and (4) the presence of interaction. In
      addition to detailed analysis steps, raw data sets are also available for readers
      to verify all the results presented. Although we only used the log-rank test and
      Cox regression for illustration purposes, the underlying concepts can be applied
      to other multivariate procedures such as the logistic regression and multiple
      linear regression.

PMID- 7641118
TI  - Animal study of phoenix total artificial heart implantation.
AB  - BACKGROUND: It is well accepted that a total artificial heart (TAH) can be used
      as a bridge to heart transplantation during the waiting period for organ
      donation. A series of combined studies, conducted by the Kaohsiung Veterans
      General Hospital, National Yang-Ming Medical College and Municipal Tainan
      Hospital, has been performed to improve the Phoenix artificial heart developed by
      Dr. Kevin Kuo-Tsai Cheng. METHODS: In growing calves (weighed about 80 kg),
      standard procedures were used to remove the hearts and replace them with the
      TAHs. Records were made of hemodynamic data, physiological responses, blood
      biochemistry data and physical activities after operation and until the death of
      the calves. Finally, autopsies were used to determine the causes of death.
      RESULTS: A total of 23 calves were studied. Twenty-two of them survived 1 to 12
      days, or an average 4.95 days. One survived more than 30 days. All the calves
      could breathe, stand, eat and void by themselves two hours after operation.
      Respiratory failure was the major cause of death. CONCLUSIONS: No thrombus within
      the TAH was noted in the last five cases, meaning that turbulent flow or dead
      space of the TAH was improved. Better intensive care and prevention of infection
      will be the next challenge for long-term use of TAH.

PMID- 7641119
TI  - Establishment of in vivo hepatoma models in rat and mouse from rodent hepatoma
      cell lines.
AB  - BACKGROUND: Hepatoma is one of the most common cancers in Southeast Asia and
      African countries. In Taiwan, it is the leading cause of death in male cancer
      patients. In order to examine the effect of various factors on the growth of
      hepatoma, in vivo hepatoma models such as carcinogen-induced hepatoma and
      subcutaneous implantation of hepatoma in nude mice have been used. However, there
      are disadvantages in these models. METHODS: Rats and mice were anesthetized by
      ketamine or ether, respectively. After a midline incision was made, N1S1 rat
      hepatoma cells were injected intrasplenically to partially hepatectomized or sham
      operated rats, while BALB/c mice received intrasplenic injection of ML-2 and ML-3
      mouse hepatoma cells. For direct tumor implantation, a 1mm3 N1S1 tumor piece was
      implanted in liver of Sprague-Dawley (SD) rat using a trocar. Animals were
      sacrificed at specific times after tumor implantation. Tumor incidence and the
      number of tumor nodules on the liver surface were recorded. Tumor samples were
      fixed and embedded for histological examination. RESULTS: After intrasplenic
      implantation of ML-2 cells, no tumor was observed on the liver in any of the 10
      mice 40 days later. In comparison, rapid growth of hepatic ML-3 tumors was
      observed in all animals. Rat hepatoma cells RH-35, McA-RH7777 and McA-RH8994
      cells did not form tumors in SD rats. The tumorigenicity of N1S1 cells in SD rats
      was dose-dependent on implanted tumor cells. In addition, hepatic N1S1 tumors
      could be obtained within a few weeks by homograft. CONCLUSIONS: We have
      successfully established in vivo hepatoma models in both the rat and the mouse.
      The murine ML-3 cells generated hepatoma in syngeneic BALB/c mice while the
      tumorigenicity of N1S1 cells in partially hepatectomized SD rats was dose
      dependent on implanted tumor cells. These in vivo rodent models will be valuable
      tools for future studies of hepatoma.

PMID- 7641120
TI  - A biopsy urease test in the detection of Helicobacter pylori: comparison of
      antral and body specimens.
AB  - BACKGROUND: This study was to compare the difference of positive rate and
      reaction time between the antrum and the body specimens in duodenal ulcer (n =
      124) and non-duodenal ulcer (n = 181) patients. METHODS: A total of 305 subjects
      with positive urease test were evaluated. During endoscopy each biopsy specimen
      from the greater curvature side of the antrum and the body was immediately
      incubated in a thermostatically controlled 37 degrees C waterbath and examined
      regularly in the first 6 h, and if there was no response, reexamined after 24
      hours. A change from orange to pinkish red was considered positive. RESULTS:
      There was no difference in the positive rate of urease test between the antrum
      and the body in patients with duodenal ulcer (95.2% vs. 94.4%); whereas, the
      positive rate was higher in the body specimens than in the antral specimens in
      patients without duodenal ulcer (p < 0.05, 97.8% vs. 89%). Antral specimens had
      more rapid color change of urease test than the body specimens patients with
      duodenal ulcer; whereas no such difference was found in patients without duodenal
      ulcer. In the antral specimens of patients without duodenal ulcer who were less
      than 60 years old, the color change was more rapid than in those older than 60
      (median 1.0 hr vs. 1.5 hr, p < 0.05). CONCLUSIONS: For better detection of H.
      pylori colonization using a urease test, it is critical to choose a suitable
      biopsy site. In non-duodenal ulcer disease, biopsy of the greater curve of the
      body has a higher detection rate than that of the antrum. In duodenal ulcer
      disease, biopsy of the antrum is better than that of the body for its quicker
      reaction.

PMID- 7641121
TI  - A comparison of antihypertensive effects between two formulations of atenolol:
      tenolol and tenormin.
AB  - BACKGROUND: Atenolol is a cardioselective beta-blocker. Tenolol is a new
      formulation of atenolol, with bioequivalence to the original atenolol (Tenormin).
      This study was designed to compare the antihypertensive effects between the two
      formulations of atenolol, Tenolol and Tenormin. METHODS: Twenty-three patients,
      with mild to moderate hypertension untreated with any antihypertensive drugs,
      were recruited. They were randomized to receive two weeks of placebo, four weeks
      of Tenolol or Tenormin (100 mg once daily) and two weeks of placebo. Then the
      treatments were crossed over for four more weeks. RESULTS: At two weeks five
      patients were excluded because their blood pressures (BP) were below 160/90 mmHg.
      The baseline BPs for the patients receiving Tenormin (162 +/- 18/97 +/- 8 mmHg)
      and Tenolol (164 +/- 17/97 +/- 9 mmHg) were not distinct. After two weeks of
      treatment with Tenormin or Tenolol, systolic BPs decreased by 12 +/- 11 mmHg and
      13 +/- 14 mmHg, respectively (p < 0.01 for both formulations). Similarly the
      diastolic BPs decreased significantly (p < 0.01) by 7 +/- 9 mmHg and 7 +/- 10
      mmHg, respectively. The hypotensive effects persisted at four weeks of treatment
      for both formulations. Reductions in systolic and diastolic BPs by treatment with
      Tenormin and Tenolol were not significantly different by two-way ANOVA analysis.
      There were no side effects in any patient throughout the study. CONCLUSIONS: The
      results indicate that the generic formulation of atenolol (Tenolol) has
      comparable antihypertensive effects as the original formulation (Tenormin).

PMID- 7641122
TI  - Clinical experience of neurosurgical reconstruction in anterior skull base
      lesions.
AB  - BACKGROUND: Surgery of the anterior skull base confronts with the life
      threatening risks of infection and cerebrospinal fluid (CSF) leakage, especially
      after extensive tumor resection. Avoidance of these complications demands a good
      intraoperative reconstruction. The technical feasibility has been demonstrated in
      previous reports. A judicious rationale of surgical principle is investigated in
      review of our patients and other series. METHODS: Fourteen cases underwent
      neurosurgical procedures involving the anterior skull base by the authors between
      June 1992 and January 1994. Five patients with trauma, 1 with inflammation, and 8
      with space-occupying lesion were included. The modality of skull base
      reconstruction and patients' outcome were evaluated. RESULTS: Eleven of these
      cases accepted reconstructive procedures to some extent including pericranium,
      lyodura, tissue glue, bone graft and muscle flaps. Four cases of traumatic CSF
      leakage were successfully repaired after anterior skull base reconstruction. One
      case with traumatic optic neuropathy restored vision after surgical optic nerve
      decompression. A rhinogenic infected discharging sinus was cured with pedicle
      island flap obliteration. Space-occupying lesions in 8 cases were totally removed
      without postoperative wound infection, CSF leakage, or meningitis, of which 2
      cases of malignancy recurred 7 and 5 months after operation respectively. The
      follow-up period was from 5 to 26 months with a mean of 14 months. CONCLUSIONS:
      Meticulous reconstruction with different possibilities of closure is the
      cornerstone of anterior skull base surgery, in spite of its difficulties and
      needs for extensive resection. Combined craniofacial resection could achieve "en
      bloc" or radical excision of "inoperable" anterior skull base lesions confidently
      with low morbidity and mortality based on skillful reconstructive techniques.

PMID- 7641124
TI  - Efficacy and safety of estriol replacement therapy for climacteric women.
AB  - BACKGROUND: As an estrogen derivative, estriol is rather effective in the relief
      of climacteric symptoms due to estrogen deficiency. When given one dose a day, it
      will not provoke endometrial proliferation and shedding. Thus, it is suitable for
      postmenopausal women who no longer want to have uterine bleeding and for those
      with comparatively higher risk of endometrial hyperplasia. In the aspect of
      postmenopausal osteoporosis, the prevention of further bone loss due to estrogen
      deficiency is also important and to be evaluated. METHODS: We collected 20
      patients, aged 44-62 years, who had undergone either natural or surgical
      menopause and were treated with estriol succinate (Synapause; Organon; Holland 2
      mg/tab) 2 mg/day for 2 years, with relief of climacteric symptoms evaluated after
      the first 3 months of treatment. Bone mineral density (BMD) of lumbar spine was
      measured using quantitative computed tomography (QCT) after one and two years of
      treatment, respectively. RESULTS: Estriol was very effective in the improvement
      of major subjective climacteric complaints in 86% of patients, especially hot
      flush and insomnia within 3 months. The atrophic genital changes caused by
      estrogen deficiency were also improved satisfactorily. No subjective symptoms
      induced by the therapy were seen. The rate of uterine bleeding was low,
      complained by only one patient. However, our study did not show the preventive
      effect of estriol against osteoporosis. CONCLUSIONS: Estriol can be a safe and
      effective alternative in the relief of climacteric symptoms for postmenopausal
      women, but it cannot prevent the bone loss.

PMID- 7641123
TI  - A clinical study of colorectal cancer accompanied by cancer of other organs.
AB  - BACKGROUND: The incidence of double primary neoplasms has increased in recent
      decades. The etiologies and epidemiologies of double primary neoplasms are under
      investigation, and relationships between some cancers are well established. A
      group of patients with double primary cancers was studied to determine the
      relationships between certain cancers. METHODS: From November 1982 to September
      1993, 48 patients with colorectal cancer accompanied by cancer of another organ
      (double primary cancers) were treated here. The male-to-female ratio was 31 to
      17. According to Warren's definitions, the patients were classified into two
      groups: synchronous and metachronous. Data collection was done on the basis of
      locations, pathological staging and interval between cancers. RESULTS: Among the
      48 patients, extracolonic cancers were mainly found in the cervix (8), stomach
      (7), prostate (5), lung (5), urinary bladder (4), and breast (4). In the female
      patients, 88.2% (15/17) of extracolonic cancers were in the female reproductive
      organs. In male patients, 45% (14/31) of extracolonic cancers were GI tract
      neoplasms, and 35.5% (11/31) were cancers of the GU tract. Nearly half of the
      patients expired within two years after diagnosis of the second primary cancer.
      CONCLUSIONS: Cancers of the cervix, stomach, prostate, lung, urinary bladder and
      breast may have some etiologic factors in common with that of colorectuim. Thus,
      attention should be paid to these sites during the period of post-operative
      follow-up of the first primary cancer.

PMID- 7641125
TI  - Preeclampsia in multiple pregnancy.
AB  - BACKGROUND: Preeclampsia is one of the most common pregnancy-induced
      complications, and results in a large number of maternal deaths. How pregnancy
      incites or aggravates hypertension remains unresolved; despite decades of
      intensive research directed to hypertensive disorders, they remain among the most
      important unresolved problems in obstetrics. The incidence of preeclampsia is
      increased in multiple pregnancies, and several preeclampsia-related fetal risks
      may be particularly hazardous to the babies of multiple gestations. METHODS: The
      records of 561 women with multiple pregnancies delivered consecutively at Mackay
      Memorial Hospital were reviewed retrospectively. Thirteen mild cases and 39
      severe cases of preeclampsia in multiple pregnancies were compared with 52
      control cases of multiple pregnancies without preeclampsia, but matched for
      maternal age and parity. The categories for comparison included parity,
      gestational age, time of onset of preeclampsia, route of delivery, mean birth
      weight, growth discordancy, maternal complications, neonatal morbidity and
      mortality. RESULTS: The incidence of preeclampsia in our consecutive series of
      561 multiple pregnancies was 9.3% compared with 1.8% in singleton pregnancies (p
      < 0.0001). In primiparas with multiple pregnancies, the incidence of preeclampsia
      was 12.2% compared with 6.2% (p < 0.05) in multiparas. Breech presentation was
      the most common indication for Cesarean section in all groups. The preeclamptic
      group had a significantly higher rate of Cesarean section compared with the
      control group (p < 0.006), with prolonged labor and fetal distress were the two
      main reasons for this difference. Severe preeclamptic patients had babies with
      significantly lower mean birth weights (p < 0.05), higher incidence of
      intrauterine growth retardation (p < 0.025) and neonatal respiratory distress
      syndrome (p < 0.0008) compared with those of the control group. All seven cases
      with maternal complications were in the severe preeclamptic group. CONCLUSIONS:
      An unfavorable perinatal outcome was found to be associated with severe, but not
      with mild, preeclampsia in multiple pregnancies.

PMID- 7641127
TI  - Unusual presentation of acute abdomen in scrub typhus: a report of two cases.
AB  - Two young soldiers presented with acute abdomens, then received surgical
      procedures under initial impression of acute cholecystitis and acute appendicitis
      respectively. Operative findings did not confirm the initial diagnosis, and the
      clinical condition did not improve after operation. Scrub typhus was suggested
      later by clinical manifestations of fever, chills, headache, lymphadenopathy,
      skin rash and presence of eschar formation; this diagnosis was finally confirmed
      by positive serologic results of high Weil-Felix OXK agglutination and/or
      Rickettsia tsutsugammushi immunoflorescence titers in paired sera. Both patients
      rapidly became afebrile after administration of tetracycline. This unusual
      presentation with acute abdomen in scrub typhus is emphasized, with caution that
      the possibility of scrub typhus should be taken considered, especially in
      patients coming from hyperendemic areas.

PMID- 7641126
TI  - Acute heroin intoxication with complications of acute pulmonary edema, acute
      renal failure, rhabdomyolysis and lumbosacral plexitis: a case report.
AB  - After intravenous injection of heroin, a 27-year-old male with altered mental
      status and hypotension was seen at the Emergency Service where acute pulmonary
      edema was noted. The problem was resolved three days later after oxygen therapy
      had been administered by face mask. Acute renal failure, rhabdomyolysis and
      monoplegia of the patient's left leg were exhibited during his stay at the
      Intensive Care Unit. Neurological examination and electro-diagnostic studies
      (electromyography and nerve conduction velocity) showed left lumbosacral
      plexitis. Hemodialysis was given. Though the patient's hospital course was
      uneventful, satisfactory recovery from his left leg weakness, which persisted for
      one year after hospital discharge, was finally achieved.

PMID- 7641128
TI  - Angiographic findings in Tolosa-Hunt syndrome: a case report.
AB  - A 71-year-old man suffered from left-side throbbing headache over the region of
      the fifth cranial nerve first division, followed by left ptosis and
      ophthalmoplegia. Under tentative diagnosis of Tolosa-Hunt syndrome (THS), oral
      prednisolone 60 mg was given daily. His headache and ophthalmoplegia dramatically
      improved within 24 hours. Magnetic resonance (MR) imaging and computed tomography
      (CT) of the head were negative. However, irregularity in the siphon of the left
      internal carotid artery was disclosed by angiography. This case illustrates that
      angiography may be useful in diagnosing THS, when CT and MR imaging are negative.

PMID- 7641129
TI  - Gastrointestinal bleeding due to whipworm (Trichuris trichiura) infestation: a
      case report.
AB  - Severe whipworm infestation, an exceedingly uncommon cause of gastrointestinal
      bleeding, has not been reported in Taiwan. The reported case concerns a 59-year
      old female who had suffered from abdominal pain and passage of tarry stool for
      several days. Esophagogastroduodenoscopy was performed, and several roundworms
      were seen in the second portion of duodenum. After removal, the characteristic
      appearance of Trichuris trichiura was apparent. After exploratory laparotomy for
      intractable bloody stool, the result of operative findings and pathological
      reports also confirmed our diagnosis. This is a case presented of massive
      gastrointestinal bleeding in which the cause of bleeding was diagnosed before
      operation to be whipworm infestation by endoscopic examination. The clinical and
      pathologic characteristics of the trichuriasis are described, with a brief review
      and discussion.

PMID- 7641130
TI  - Psoas abscess due to mucinous cystadenocarcinoma of the appendix: a case report.
AB  - Psoas muscle abscess is an uncommon and challenging entity. The present report
      describes a 64-year-old man presenting with right flank mass. Abdominal
      computerized tomography showed a right psoas abscess. Extraperitoneal drainage
      was performed, and pathology revealed metastatic mucinous adenocarcinoma. After
      further study, laparotomy and right hemicolectomy were performed under the
      impression of colon cancer. The final pathology showed mucinous
      cystadenocarcinoma of appendix. The literature about the etiology, diagnosis and
      treatment of psoas abscess are reviewed. Additionally, the treatment and
      prognosis for mucinous cystadenocarcinoma of the appendix are noted.

PMID- 7641131
TI  - Lumboperitoneal shunt complicated with chronic tonsillar herniation: a case
      report.
AB  - Lumbopritoneal shunt (L-P shunt) has been widely accepted as a treatment for
      communicating hydrocephalus. The technique offers many advantages such as easy
      insertion, a low infection rate, a reduced incidence of brain damage, et centera.
      Despite these advantages, there are also some associated complications, such as
      tonsillar herniation. This complication rarely occurs, but, when it does, it
      develops gradually. This report concerns an eight-year-old girl, who had received
      L-P shunt at the age of 20 days; she then developed tonsillar herniation,
      requiring operative decompression, eight years later. This case illustrates the
      necessity for carefully follow up patients who have undergone the L-P shunt
      procedure.

PMID- 7641132
TI  - A joint hospital/vendor project brings CQI and point-of-care technology to home
      care.
AB  - A joint project team consisting of personnel from Parkview Episcopal Medical
      Center, Pueblo, Colorado, and Patient Care Technologies, Atlanta, Georgia, a
      software vendor, codeveloped a point-of-care based system of electronic patient
      records and administrative data capture for home health care. Well established
      continuous quality improvement techniques, in use at Parkview for approximately 6
      years, guided the development project and the subsequent alpha and beta testing
      of the system. Significant results to date include an overall productivity gain
      approaching 20%, the potential to increase annual home care revenue $876,000 with
      the same staffing level, and an 83% reduction in billing errors. Although not
      directly measured as a part of the study, the project team believes the quality
      of charting has improved because it is now done at the point-of-care in the home
      rather than in the office--some period of time after care is delivered.
      Anticipated future development includes integration of the home care clinical
      record with the hospital's clinical data repository and explicit support of
      critical pathways.

PMID- 7641133
TI  - A clinical information system for ambulatory care.
AB  - This article describes a clinical information system developed for ambulatory
      care nurse practitioners. An overview of the clinical information system is
      presented, followed by a detailed description. The clinical information system
      uses the relational database structure proposed by Hettinger and Brazile (1992),
      and creates a longitudinal electronic health care record. The database design
      includes the Nursing Minimum Data Set and provides links to external aggregate
      data sets such as the U. S. Census data. Special features are discussed such as
      the ability to select from several problem classification schemes, including
      North American Nursing Diagnosis Association, Omaha, and International
      Classification of Diseases, 9th Revision; insert new menu selections whenever
      needed; create and track groups; and store detailed outcome data. A brief summary
      of implementation considerations is included.

PMID- 7641134
TI  - Accessing nursing resources on the Internet.
AB  - Nurses and other health professionals have recognized the exponential increase in
      published nursing, medical, scientific, and allied health literature. The
      Internet is adding more information to that expanse. Information specialists and
      librarians have noted that although a virtually limitless range of health
      information is present on the Internet's discussion lists, file transfer
      protocol, telnet, gopher, and World Wide Web sites, computer users are just
      beginning to use the "information super-highway." This article describes the uses
      of the Internet while providing practical information addressing questions of
      connecting to the network and searching its most useful features.

PMID- 7641135
TI  - Factors that contribute to computer-assisted instruction effectiveness.
AB  - This article describes factors that contribute to the effectiveness of computer
      assisted instruction as a teaching strategy. According to the literature
      reviewed, three major variables that can influence computer-assisted instruction
      are the quality of the software programs, the environment of use of the computer,
      and the characteristics of the learner. The nurse educator should be aware of the
      significance of each variable to provide an optimal learning experience for the
      students.

PMID- 7641136
TI  - Multimedia training in nursing education.
AB  - The new developments in computer technology are changing the way training
      professionals look at computer-assisted instruction (CAI). Nursing educators and
      practitioners can plan on CAI capabilities that will be both possible and
      economical as well as within the reach of most organizations. Health care
      delivery may not be in a position to forego multimedia training as part of its
      repertoire. In this article, we review interactive video instruction as a
      multimedia tool in nursing education with an emphasis on the new developments in
      hardware and software technology. In particular, we examine the changing role of
      CD-ROM technology and how it has become a tool to change the face of CAI. We
      define the current status and future trends in CAI and interactive video
      instruction for nursing education. Several key definitions are introduced to
      reflect the new direction of multimedia in nursing education.

PMID- 7641137
TI  - Applied information technology: a clinical perspective. Feature focus: the
      Computer-based Patient Record (Part 3).

PMID- 7641138
TI  - The evolution of invasion by enteric bacteria.
AB  - Despite differences in disease pathologies and host range, many enteric
      pathogens, including Salmonella and Shigella spp., utilize a remarkably similar
      machinery to secrete proteins that promote their entry into host cells. Analogous
      structures are required for the export of virulence proteins in other animal and
      plant pathogens. While the structure and organization of the gene complexes
      specifying these secretory pathways are broadly conserved, their phylogenetic
      distribution and genomic locations suggest that these sequences arose
      independently in divergent pathogens.

PMID- 7641139
TI  - Characterization of monoclonal antibodies to Yersinia enterocolitica iron
      regulated proteins.
AB  - Yersinia enterocolitica 1165 (0:8) expressed several iron-regulated proteins with
      molecular masses of 240, 194, 80, 79, 70, and 67 kDa. These proteins were not
      detected in cells grown in iron-rich conditions. Cell surface iodination
      indicated that the 240- and 190-kDa proteins (HMWPs) were not surface exposed,
      whereas the 67- and 70-kDa proteins appeared to be exposed to the cell surface.
      Incubation with iron protected the 67- and 70-kDa proteins from proteinase K
      treatment, suggesting that they may be involved in iron acquisition. Monoclonal
      antibodies (MAbs) were produced against the HMWPs and the 67-kDa iron-regulated
      protein. MAbs to the HMWPs not only recognized the 240- and 194-kDa proteins but
      also reacted with the 67- and 70-kDa iron-regulated proteins. Similarly, MAbs to
      the 67-kDa protein reacted with the 67- and 70-kDa proteins and the HMWPs,
      suggesting that these iron-regulated proteins are related immunologically. In
      addition, the MAbs recognized the 67- and 70-kDa proteins and HMWPs from other Y.
      enterocolitica serotypes, suggesting that the antigenic sites recognized on these
      iron-regulated proteins are conserved. The MAbs examined did not inhibit iron
      binding or iron uptake and did not provide protection against a Y. enterocolitica
      1165 (0:8) infection in a systemic mouse infection model. Although these MAbs
      were not protective in this model, these iron-regulated proteins may play a role
      in iron acquisition and virulence, but the MAbs examined are probably not
      directed against epitopes involved in iron acquisition or virulence.

PMID- 7641140
TI  - Repression of motility and flagellin production at 37 degrees C is stronger in
      Listeria monocytogenes than in the nonpathogenic species Listeria innocua.
AB  - Listeria monocytogenes and Listeria innocua differ markedly in virulence but are
      indistinguishable by classical taxonomic criteria. Both species are actively
      motile and produce abundant flagellin at 22 degrees C. We have found, however,
      noticeable differences between L. monocytogenes and L. innocua in motility and
      flagellin production at 37 degrees C. At this temperature, L. monocytogenes
      strains were virtually nonmotile and produced little or no detectable flagellin,
      whereas strains of L. innocua were frequently motile and produced substantial
      amounts of flagellin. This flagellin was recognized by a Listeria genus-specific
      monoclonal antibody that also recognized flagellin produced at 22 degrees C.
      These results suggest differential regulation of flagellin production between L.
      monocytogenes and L. innocua at 37 degrees C.

PMID- 7641141
TI  - Investigation of the lignin-degrading activity of Serratia marcescens:
      biochemical screening and ultrastructural evidence.
AB  - Forty-one morphologically distinct bacterial isolates were developed from six
      lignin-containing environments. Each isolate was initially screened for potential
      lignin-degrading activity using relative growth on a lignocellulosic substrate
      and relative decolorization of a polymeric dye. Screened isolates were then
      tested for the ability to oxidize various lignin-related monomers, and the dimers
      anisoin and veratrylglycerol-beta-guaiacyl ether. Although most of the isolates
      oxidized the monomers, only two successfully oxidized the dimers. The dimer
      degrading isolates were tested for extracellular activity against the beta-O-4
      dimer veratryl-glycerol-beta-guaiacyl ether. No activity was detected for the
      isolates. Phanerochaete chrysosporium Burds used as a positive control
      demonstrated a high degree of activity in each assay. Extensive ultrastructural
      studies of lignocellulose alteration by the dimer-degrading isolates were
      conducted via light and transmission electron microscopy. These studies indicate
      that one of the isolates, identified as Serratia marcescens, is capable of
      degrading highly lignified secondary cell wall components. This activity is
      localized, apparently requiring direct contact between cells and substrate, which
      could be facilitated by an associated glycocalix. The results of the dimer
      degradation assays concur with the characterization of the responsible enzyme
      system as being membrane associated.

PMID- 7641142
TI  - Effects of leader sequences upon the heterologous expression of restrictocin in
      Aspergillus nidulans and Aspergillus niger.
AB  - The effects of altered leader sequences on the secretion and localization of
      restrictiocin expression in Aspergillus nidulans and Aspergillus niger were
      investigated. The region encoding the leader sequence of the Aspergillus
      restrictus restrictocin (res) gene was altered and variants were expressed under
      the glucoamylase (glaA) promoter in A. nidulans and A. niger. The entire
      restrictocin leader sequence was replaced by the glaA leader sequence in one
      variant. In another, the signal sequence of restrictocin was replaced with the
      glaA signal, leaving a hybrid with the putative restrictocin pro region in place
      of the glaA pro region. The putative pro region was deleted from the restrictocin
      leader of a third variant. Toxic effects, such as reduced transcript levels and
      cellular lysis, were minimal when restrictocin was expressed with the native
      leader sequence, but became more pronounced as the leader sequence was varied.
      These toxic effects were inversely proportional to the level of restrictocin
      secreted. In all transformed strains, restrictocin secretion appeared at the
      periphery of colonies and was observed to occur at the tips of hyphae.
      Localization of restrictocin to differentiated structures (conidiophores), as
      occurs in A. restrictus, was observed only in transformed strains containing the
      complete restrictocin leader sequence.

PMID- 7641143
TI  - Characterization by arbitrary primer polymerase chain reaction of polychlorinated
      biphenyl (PCB)-degrading strains of Comamonas testosteroni isolated from PCB
      contaminated soil.
AB  - In this study, we isolated and characterized biphenyl (BP) and polychlorinated
      biphenyl (PCB) degrading bacterial strains found in PCB-contaminated soil from an
      auto manufacturing plant located in Syracuse, New York. Twenty-one BP and PCB
      degrading bacteria were randomly selected to form a representative sample of the
      bacterial population present at the site. Of the 21 bacteria, 13 were identified
      as Comamonas testosteroni, constituting about 60% of the bacterial population
      examined. Other PCB degraders identified were Acidovorax facilis, Alcaligenes
      xylosoxydans, Bacillus sphericus, Hydrogenophaga pseudoflava, Pseudomonas avanae,
      and Rhodococcus fascians. Owing to the abundance of C. testosteroni at this site,
      only these isolates were further characterized for their PCB congener degradation
      profile, 2,3-dihydroxybiphenyl 1,2-dioxygenase activity, and genetic relatedness
      by polymerase chain reaction (PCR) analysis. The PCB congener degradation pattern
      revealed a high degree of variability among the C. testosteroni isolates. The
      majority of the C. testosteroni isolates tested could degrade more than 95% of
      the PCB congeners up to pentachlorinated biphenyl. Only four isolates could
      degrade more than 80% of hexachlorobiphenyl. All 12 isolates of C. testosteroni
      tested were able to attack 2,3,4,5,6,3',4'-heptachlorobiphenyl, indicating
      involvement of biphenyl 2,3-dioxygenase, while 2,3,5,6,2',3',6'
      heptachlorobiphenyl was attacked by 6 strains, suggesting an oxidation reaction
      mediated by 3,4-dioxygenase. 2,3-Dihydroxybiphenyl 1,2-dioxygenase activity was
      also found to vary among the C. testosteroni isolates tested in this study.
      Eleven strains showed 2,3-dihydroxybiphenyl 1,2-dioxygenase activity specific for
      2,3-dihydroxybiphenyl, whereas isolate BW 169 could metabolize both 2,3
      dihydroxybiphenyl and 4-methylcatechol, and isolate BW74 had the ability to
      metabolize all three substrates (2,3-dihydroxybiphenyl, 4-chlorocatechol, and 4
      methylcatechol).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7641144
TI  - Replication of measles virus in human monocytes and T cells.
AB  - Replication of measles virus (MV) in populations of peripheral blood mononuclear
      cells enriched for T cells and monocytes was studied using a temperature
      sensitive mutant, MV ts38, and the parent counterpart, MV Lec. Stimulation of the
      cells was required for a full cycle of virus replication in both cell types. More
      infectious virus was released after stimulation from MV-infected populations
      enriched for T cells, T cell-enriched than from monocyte-enriched populations.
      However, similar amounts of viral mRNA, genomic RNA, and viral proteins of the
      expected size were found in both cell populations. The results indicate that MV
      specific macromolecular synthesis is similar in both T cells and monocytes, but
      the assembly and (or) release of infectious virus is greatly reduced in monocytes
      as compared with T cells.

PMID- 7641145
TI  - Purification of sex pheromones specific for pMB1 and pMB2 plasmids of
      Enterococcus faecalis S-48.
AB  - The strain Enterococcus faecalis S-48 carries two large conjugative plasmids
      (pMB1 and pMB2) encoding for antagonistic substances. The pheromone response of
      these two plasmids was established by purifying the corresponding sex pheromones,
      using conventional reversed-phase columns. Plasmid pMB1 responds to pheromone
      cCF10. Plasmid pMB2 responds to a pheromone with an amino acid sequence identical
      to that of cPD1 (Phe-Leu-Val-Met-Phe-Leu-Ser-Gly). The two pheromone-responding
      plasmids coexist in a stable fashion in the wild-type strain E. faecalis S-48.

PMID- 7641146
TI  - Bacterial succession within a biofilm in water supply lines of dental air-water
      syringes.
AB  - Biofilms have been implicated as reservoirs for bacterial contamination of water
      delivered by dental air-water syringes. A 6-month study was done of bacterial
      colonization and biofilm formation in plastic water supply lines connected to
      dental air-water syringes. Changes in biofilm flora were observed by both
      scanning electron microscopy and bacteriologic culture. By day 7, many rod- and
      spiral-shaped bacteria had colonized the ridged surface of the luminal wall of
      the tubing, as revealed by scanning electron microscopy. By day 30, individual
      microcolonies were embedded in extracellular polymeric material. By day 120,
      these microcolonies had begun to coalesce, and by day 180 the biofilm had
      developed into a multilayered, heterogeneous mixture of microcolonies. The mean
      aerobic plate counts of colony-forming units of planktonic and biofilm
      populations were, in log10 values, 5.9 +/- 0.54/mL and 4.2 +/- 0.82/cm2,
      respectively. Early colonizers were predominantly Pseudomonas spp., but included
      Pasteurella, Moraxella, Ochrobactrum, and Aeromonas spp. Flavobacterium and
      Acinetobacter spp. were observed later. Many of these organisms are opportunistic
      pathogens. These results demonstrate the longitudinal dynamics of biofilm
      formation.

PMID- 7641147
TI  - Prescribing for elderly people in NB: where do the figures point?

PMID- 7641148
TI  - Good practices make good medicine.

PMID- 7641149
TI  - Pregnant mare's urine: welfare or rights for animals?

PMID- 7641150
TI  - HIV transmission: rights of workers and patients.

PMID- 7641151
TI  - The impact of unemployment on health: a review of the evidence.
AB  - OBJECTIVE: To review the scientific evidence supporting an association between
      unemployment and adverse health outcomes and to assess the evidence on the basis
      of the epidemiologic criteria for causation. DATA SOURCES: MEDLINE was searched
      for all relevant articles with the use of the MeSH terms "unemployment,"
      "employment," "job loss," "economy" and a range of mortality and morbidity
      outcomes. A secondary search was conducted for references from the primary search
      articles, review articles or published commentaries. Data and definitions of
      unemployment were drawn from Statistics Canada publications. STUDY SELECTION:
      Selection focused on articles published in the 1980s and 1990s. English-language
      reports of aggregate-level research (involving an entire population), such as
      time-series analyses, and studies of individual subjects, such as cross
      sectional, case-control or cohort studies, were reviewed. In total, the authors
      reviewed 46 articles that described original studies. DATA EXTRACTION:
      Information was sought on the association (if any) between unemployment and
      health outcomes such as mortality rates, specific causes of death, incidence of
      physical and mental disorders and the use of health care services. Information
      was extracted on the nature of the association (positive or negative), measures
      of association (relative risk, odds ratio or standardized mortality ratio), and
      the direction of causation (whether unemployment caused ill health or vice
      versa). DATA SYNTHESIS: Most aggregate-level studies reported a positive
      association between national unemployment rates and rates of overall mortality
      and mortality due to cardiovascular disease and suicide. However, the relation
      between unemployment rates and motor-vehicle fatality rates may be inverse.
      Large, census-based cohort studies showed higher rates of overall mortality,
      death due to cardiovascular disease and suicide among unemployed men and women
      than among either employed people or the general population. Workers laid off
      because of factory closure have reported more symptoms and illnesses than
      employed people; some of these reports have been validated objectively.
      Unemployed people may be more likely than employed people to visit physicians,
      take medications or be admitted to general hospitals. A possible association
      between unemployment and rates of admission to psychiatric hospitals is
      complicated by other institutional and environmental factors. CONCLUSIONS:
      Evaluated on an epidemiologic basis, the evidence suggests a strong, positive
      association between unemployment and many adverse health outcomes. Whether
      unemployment causes these adverse outcomes is less straightforward, however,
      because there are likely many mediating and confounding factors, which may be
      social, economic or clinical. Many authors have suggested mechanisms of
      causation, but further research is needed to test these hypotheses.

PMID- 7641152
TI  - Fetal tissue transplantation and abortion decisions: a survey of urban women.
AB  - OBJECTIVE: To describe women's attitudes and predicted behaviour regarding the
      potential for fetal tissue transplantation (FTT) to influence abortion decisions.
      DESIGNS: Self-administered questionnaire survey by mail. SETTING: Academic family
      practice in Toronto. PARTICIPANTS: Random sample of 475 women 18 to 40 years of
      age selected from the family practice registry of an urban teaching hospital.
      Family physicians were blind to their patients' participation, and investigators
      were blind to the subjects' identity. Forty questionnaires were undeliverable. Of
      the remaining 435, 272 (62.5%) were completed. Six of the women were over 40
      years of age or did not indicate their age and were excluded, which left 266
      (61.1%) questionnaires for analysis. OUTCOME MEASURES: Number of women who would
      (a) be more likely to have an abortion if they could donate tissue for FTT and
      (b) feel better or worse about choosing abortion if FTT were an option, and open
      ended comments about the potential for FTT to influence abortion decisions.
      RESULTS: Of the 266 respondents 32 (12.0%) reported that they would be more
      likely to have an abortion if they could donate tissue for FTT, 178 (66.9%)
      stated that they would not be more likely to do so, and 56 (21.1%) were
      uncertain. Of the 122 who indicated that they would consider an abortion if they
      were pregnant, 21 (17.2%) stated that they would be more likely to have an
      abortion if they could donate tissue for FTT, 77 (63.1%) replied that they would
      not be more likely to do so, and 24 (19.7%) were uncertain. The women 25 to 33
      years of age were more likely to be influenced by FTT than the younger or older
      women, and the women 18 to 24 years were more uncertain about the influence of
      FTT on abortion decisions than the older women. In written responses some of the
      women felt that FTT might make abortion decisions easier; many were troubled that
      FTT might be used to justify a morally problematic abortion decision and felt
      that FTT should not be used to justify abortion. CONCLUSION: The data, the first
      of their kind gathered from from women, suggest that some women's abortion
      decisions may be influenced by the option to donate tissue for FTT. Further
      research is necessary to explore the mechanism of influence.

PMID- 7641153
TI  - Interactions with the pharmaceutical industry: experiences and attitudes of
      psychiatry residents, interns and clerks.
AB  - OBJECTIVE: To examine the type and number of interactions of psychiatry
      residents, interns and clerks with sales representatives of pharmaceutical
      companies and the attitudes of physicians-in-training toward these interactions.
      DESIGN: Survey conducted with the use of a self-report questionnaire. SETTING:
      Seven teaching hospitals affiliated with the Department of Psychiatry, University
      of Toronto. PARTICIPANTS: All 105 residents, interns and clerks training in
      psychiatry at the seven teaching hospitals between October 1993 and February 1994
      were eligible; 74 completed questionnaires, for a response rate of 70%. One
      respondent was excluded from the analysis. OUTCOME MEASURES: Number of personal
      meetings and "drug lunches" attended, number of drug samples and promotional
      items received and estimated value of gifts received by each physician-in
      training during a 1-year period as well as attitudes of residents, interns and
      clerks about interactions with pharmaceutical representatives. RESULTS: Median
      number of personal meetings reported was 1 (range 0 to 35), of drug lunches
      attended was 10 (range 0 to 70), of promotional items received was 2 (range 0 to
      75) and of drug samples received was 1 (range 0 to 20). Trainees' median estimate
      of the value of gifts received was $20 (range $0 to $800 Fewer than one third
      felt that pharmaceutical representatives were a source of accurate information
      about drugs; however, 71% (52/73) disagreed with the statement that
      representatives should be banned from making presentations. Although only 15%
      (11/73) felt they had sufficient training about meeting with pharmaceutical
      representatives, 34% (25/73) felt that discussions with representatives would
      have no impact on their prescribing practices, and 56% (41/73) felt that
      receiving gifts would have no impact on prescribing. Fewer than half said they
      would maintain the same degree of contact with representatives if they did not
      receive promotional gifts. The more money and promotional items a physician-in
      training had received, the more likely he or she was to believe that discussions
      with representatives did not affect prescribing (p < 0.05). Clerks, interns and
      junior (first-year and second-year) residents attended two to three times more
      drug lunches than senior (third-year and fourth-year) residents, and
      significantly more junior than senior residents felt that pharmaceutical
      representatives have a valuable teaching role. Junior residents were three times
      more likely than senior residents to have received drug samples. CONCLUSIONS:
      Interactions between pharmaceutical representatives and psychiatry residents,
      interns and clerks are common. The physicians-in-training perceive little
      educational value in these contacts and many, especially clerks, interns and
      junior residents, disavow the potential of these interactions to influence
      prescribing. Therefore, supervisors of postgraduate medical training programs may
      wish to provide instruction concerning potential conflicts of interest inherent
      in these types of interactions.

PMID- 7641155
TI  - The Brandes-Friesen case reports: how should we interpret the news?
AB  - In this issue (see pages 561 to 566 two case reports by Lorne J. Brandes and
      Linda A. Friesen illustrate a temporal relation between the discontinuation or
      initiation of therapy with certain non-antineoplastic agents (lithium,
      carbamazepine and an H1-antihistamine) and the clinical course of cancer. Only an
      accumulation of similar case reports and the results of epidemiologic and
      controlled clinical studies will show whether the temporal relation observed in
      these cases is also a causal one. In the absence of strong, let alone conclusive,
      evidence that antidepressants or antihistamines promote the growth of tumours in
      human beings, a recommendation to stop using these medications would be
      premature. The news about these case reports and about animal studies on the
      tumour-promoting potential of some antidepressants and antihistamines is likely
      to spread through the media. The realistic and responsible option for physicians
      and clinical investigators is to help patients and prospective participants in
      clinical trials to interpret this information in a balanced and reasonable
      fashion.

PMID- 7641154
TI  - Can the clinical course of cancer be influenced by non-antineoplastic drugs?
AB  - Laboratory and anecdotal clinical evidence suggests that some common non
      antineoplastic drugs may affect the course of cancer. The authors present two
      cases that appear to be consistent with such a possibility: that of a 63-year-old
      woman in whom a high-grade angiosarcoma of the forehead improved after
      discontinuation of lithium therapy and then progressed rapidly when treatment
      with carbamazepine was started, and that of a 74-year-old woman with metastatic
      adenocarcinoma of the colon that regressed when self-treatment with a
      nonprescription decongestant preparation containing antihistamine was
      discontinued. The authors suggest that epidemiologic studies are needed to
      investigate a possible association between non-antineoplastic drugs and the
      clinical course of cancer and that consideration should be given to discontinuing
      all nonessential medications for patients with cancer.

PMID- 7641156
TI  - Reflections on supply-demand mismatch in dialysis services in Ontario.
AB  - The population-based dialysis rate in Ontario more than doubled between 1981 and
      1992; yet there is concern about over-loaded facilities, delayed treatment and
      denial of dialysis through nonreferral and implicit rationing. A working party
      involving several stakeholders has been established in Ontario to address these
      issues. However, clinical policy making concerning dialysis services is impeded
      in all provinces by a lack of information. The causes of the moderately large
      variations in dialysis rates from province to province remain unclear. The exact
      extent and risks of delayed therapy have not been well defined. Dialysis
      protocols vary inexplicably among centres, and cost data on different methods of
      providing dialysis are limited. Many steps could be taken in Ontario and other
      provinces to generate a better information base for planning and managing
      dialysis services. Predialysis clinics with outreach programs could help to
      ensure equitable access to this life-saving therapy. Criteria for choosing modes
      and intensities of renal-replacement therapy must be reviewed. In areas of clear
      disagreement and uncertainty, patients could be randomly assigned to different
      protocols and outcomes studied. In areas of agreement, the criteria should be
      standardized. Advance directives may help ascertain patients' wishes concerning
      the initiation or continuation of dialysis, and more accurate data on prognosis
      of different patient subgroups would aid in early identification of patients in a
      hopelessly deteriorating situation. Last, studies comparing the "output" (e.g.,
      hours on hemodialysis) per dollar of different dialysis units and modalities are
      also needed to ensure that all facilities are opening efficiently without
      compromising patient outcomes.

PMID- 7641157
TI  - A question of rhythm: recent advances in growth hormone research.
AB  - Research by Dr. Gloria Shaffer Tannenbaum at the McGill University-Montreal
      Children's Hospital Research Institute has led to the development of a new test
      to differentiate children who are deficient in growth hormone from those who are
      short but growing normally. This clinical application is the fruit of
      Tannenbaum's discovery that growth hormone secretion occurs in a rhythmic pattern
      regulated by intricate interactions between two neurohormones: growth hormone
      releasing hormone (GHRH) and somatotropin release-inhibiting factor (SRIF). In
      the test an analogue of SRIF is used to allow stores of growth hormone to build
      up. A subsequent challenge with GHRH is then used to identify children with a
      genuine deficiency. Tannenbaum's research also indicates that there are sexual
      differences in the pattern of growth hormone release and that growth hormone
      regulates its own secretion by means of a negative feedback system.

PMID- 7641158
TI  - Statement on influenza vaccination for the 1995-96 season. National Advisory
      Committee on Immunization.

PMID- 7641159
TI  - Anesthetist receives jail sentence after patient left in vegetative state.
AB  - A former Saskatchewan anesthetist is the first Canadian doctor to be jailed as a
      result of criminal negligence causing bodily harm. He received a 6-month jail
      sentence after a 17-year-old patient was left in a vegetative state after an
      operation. The anesthetist had left the operating room during the procedure and
      the patient became disconnected from his respirator. Dr. Dennis Kendel, registrar
      of the College of Physicians and Surgeons of Saskatchewan, says that the sentence
      "sends a very clear signal to physicians."

PMID- 7641160
TI  - Where is the silver lining? Anxious doctors ask.
AB  - When Nova Scotia elected a Liberal government in September 1993, a wave of
      optimism washed over the province's medical community. One of their own, Dr. John
      Savage, was now premier, and another, Dr. Ron Stewart, was minister of health.
      However, anticipation soon turned to anger as Stewart took aim at physician fees
      and hospital costs to help reduce the province's health care budget by $62
      million. Last November, relations between him and the Medical Society of Nova
      Scotia (MSNS) hit bottom. In an uncharacteristically political move, the society
      launched an ad campaign featuring slogans such as "Death by 1000 cuts" and "Uncle
      Sam want me. Ron Stewart doesn't." Four months later, the health department and
      the MSNS called a truce, with an agreement that many physicians consider a
      positive step. Today the province and its doctors are speaking again, and the
      medical society is working hard to help define physicians' roles in a new,
      regionalized health care system. But has the mood of doctors really improved?
      Last spring, CMAJ interviewed a cross section of Nova Scotia physicians to find
      out.

PMID- 7641161
TI  - Past presidents join forces to refurbish gravesite of Sir Charles Tupper, first
      CMA president.
AB  - The CMA's past presidents have donated a plaque and refurbished the headstone and
      plot at the Halifax gravesite of Sir Charles Tupper, the association's first
      president. "Sir Charles Tupper was a very significant personality in the
      conception of a national medical association and the past presidents wanted that
      fact to be remembered," Dr. Athol Roberts says of the endeavour.

PMID- 7641162
TI  - My father's life.
AB  - Medicine has many unsung heroes, and among them are physicians who spend their
      careers providing medical care in remote areas. In this article, Ronald Porth
      remembers the life of his father, Dr. Frank Porth, who for more than 30 years
      provided medical care on native reserves and in rural parts of the Prairies.

PMID- 7641163
TI  - CMA-cosponsored conference raises many questions about future of regionalized
      health care.
AB  - Is regionalization better because it's cheaper? Or because it provides better
      outcomes? Or simply because it's different from whatever went before? Those were
      some of the questions asked during a recent conference cosponsored by the CMA and
      Queen's University. With each successive speaker, says Charlotte Gray, the
      message became clearer: there are more muddled theories behind the trend and more
      pitfalls ahead than planners ever expected when they embarked on the exercise to
      decentralize health care in Canada and elsewhere.

PMID- 7641164
TI  - Psychiatrists campaign to attract colleagues to treat HIV-disease patients.
AB  - The shortage of psychiatrists willing to treat patients with HIV infection has
      become so severe the Canadian Psychiatric Association has launched a campaign to
      try and encourage more specialists to enter the field. At the heart of the
      campaign is a booklet, Consultant/Mentor Directory for HIV Disease and
      Psychiatry, that provides a network of 40 psychiatrists across the country who
      regularly deal with HIV-infected patients. They want to encourage colleagues to
      do the same. "There aren't a lot of psychiatrists seeing people with HIV
      disease," maintains Dr. Allan Peterkin, chair of the CPA Working Group on HIV
      Disease and Psychiatry. He worries that the shortage has led to some
      "ghettoization" of treatment.

PMID- 7641165
TI  - Forensic dentistry joins DNA analysis as important tool for police work.
AB  - A Vancouver dentist who works as a teacher, researcher and administrator at the
      University of British Columbia has a unique extracurricular interest. Dr. David
      Sweet, one of four forensic odontologists in Canada, has put names to
      unidentified bodies and the remains of car-crash victims, helped convict child
      abusers and provided evidence in robbery cases.

PMID- 7641166
TI  - Requests approaching 50,000 annually for emergency drug release program.
AB  - Health Canada's Emergency Drug Release Program, which allows physicians to
      acquire nonmarketed drugs to treat people with HIV infection, AIDS and other
      illnesses, handles about 44 000 requests annually. The executive director of the
      Drugs Directorate says the program's name is a misnomer, since few of the
      requests involve medical emergencies. Dr. Philip Berger, who uses the program for
      his AIDS patients, complains that the amount of paperwork required is oppressive.
      A government spokesperson says changes may be made to make the program less
      labour intensive.

PMID- 7641167
TI  - Northern practices offer a challenge but few MDs willing to make the move.
AB  - Manitoba's Norway House offers a ruggedly beautiful location and a challenging
      medical practice, but the physical and professional appeal has not been strong
      enough to entice physicians to make a long-term commitment to the community,
      which has needed medical service since September 1994. A physician who left there
      this spring said concerns about practice restrictions convinced him to move
      south.

PMID- 7641168
TI  - Leaner health care budgets prompt hospitals to Toronto area to pool resources.
AB  - Tighter health care budgets are prompting dozens of hospitals in the Toronto area
      to work together to become more efficient and save money. Projects range from
      sharing physicians' expertise to combining forces to make equipment purchases. As
      budgets become tighter, more large-scale projects are likely.

PMID- 7641169
TI  - Computer-assisted bone age assessment based on features automatically extracted
      from a hand radiograph.
AB  - This paper presents a computer-aided classification algorithm to assist the
      radiologist in the bone age assessment of pediatric patients. The classification
      is based on features automatically extracted from two regions of Computed
      Radiography (CR) left hand wrist images: phalangeal region of interest (PROI) and
      carpal bone region of interest (CROI). Due to imprecise nature of the bone age
      assessment problem, a fuzzy classifier for both regions has been developed. After
      defining a membership function for each region, features are processed yielding a
      matrix which maps the set of features to a year of age within the predefined
      range. The grades of membership are described as membership function values in
      the interval [0, 1]. A classification rule based on a max-sum operator, processes
      the matrix assessing the bone age. Since both regions are analyzed independently,
      two bone age assessments are obtained. They reflect the phalangeal and carpal
      bones maturity individually. In pathological cases the discrepancy between both
      assessments may reach as much as 2 yr.

PMID- 7641170
TI  - Preliminary time-flow study: comparison of interpretation times between PACS
      workstations and films.
AB  - Toshiba Hospital installed a PACS and RIS in the diagnostic imaging department
      along with a hospital-wide HIS in May 1993. Our PACS includes three diagnostic
      workstations each of which is provided with six monochrome CRT monitors. The
      diagnostic workstations have been used as the primary tools for interpretation of
      almost all radiographic images. The actual image interpretation time was measured
      for diagnostic workstations (237 examinations) and for conventional hard-copy
      films (219 examinations) for CR, CT, and MRI. The difference in interpretation
      times between diagnostic workstations and films was not significant. With regard
      to image interpretation time, diagnostic workstations are thought to be
      acceptable for practical image reading.

PMID- 7641171
TI  - Morphology-based interpolation for 3D medical image reconstruction.
AB  - Interpolation is an important processing step in 3D reconstruction. A new method,
      based on mathematical morphology, is presented here to implement the
      interpolation by means of a combined operation of weighted dilation and erosion.
      Compared with previously proposed methods, the new approach successfully resolves
      the interpolation problem when there is no overlapping area between the two
      objects. In the mean time, it has a wide adaptability and is easy to implement.

PMID- 7641172
TI  - Clinical evaluation of newly developed CRT viewing station: CT reading and
      observer's performance.
AB  - The clinical performance of the new viewing station with six CRT monitors (17
      inch, 1,024 x 1,280) was evaluated. In the primary interpretation of CT images,
      time measurements were carried out for eight radiologists. No significant
      differences in reading time existed between CRT and film in 3 of 4 readers in
      head CT series, and in 2 of 6 readers in body CT series. Compared with the
      previous system, the new prototype system achieved an approximately 30% decrease
      in reading time in both head and body CT studies and could reduce mental and eye
      fatigue.

PMID- 7641173
TI  - Quantitative contrast media dose evaluation for cranial computed tomography.
AB  - The goal of this study was to quantitatively evaluate the CT enhancement
      characteristics of selected intracranial blood vessels using four different
      volumes of a contrast medium under otherwise identical conditions in order to
      help determine a cost-effective dose. In a double blind, prospective manner, 100
      patients referred for contrast-enhanced cranial CT were randomly assigned to
      receive one of four different volumes (50, 75, 100 or 120 ml) of ioversol 320 mg
      I/ml which was subsequently administered intravenously at a rate of 1 ml/s via a
      power injector. Unenhanced images were also obtained. Scanning times, slice
      thickness and other parameters were identical in all patients. Scanning was
      initiated immediately following delivery of the full volume of contrast. Region
      of interest Hounsfield unit measurements were acquired in a standardized manner
      using a 1 mm diameter circle on the pre- and post-contrast scans of the
      supraclinoid left internal carotid artery (LICA), supraclinoid right internal
      carotid artery (RICA), basilar artery (BA), and torcular region (TR). The mean
      enhancement value (in Hounsfield units) for the 50 ml, 75 ml, 100 ml and 120 ml
      dose groups respectively were as follows for each vessel: LICA 29.9, 41.5, 63.9,
      64.6; RICA 30.1, 39.4, 62.6, 65.1; BA 30.0, 41.7, 66.0, 71.9; TR 31.7, 46.8,
      68.9, 74.3. There was no statistically significant (p > 0.05) difference in
      enhancement in any of the four vessels when the 120 ml volume was delivered
      compared to the 100 ml volume. However, there was a statistically significant (p
      < 0.05) improvement in enhancement in all four vessels when 100 ml of contrast
      was administered compared to 75 ml.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7641174
TI  - Visualizing the evolution of abnormal metabolic networks in the brain using PET.
AB  - By applying novel statistical methods and visualization techniques to PET data
      obtained from combined groups of patients and normals, we are able to illustrate
      topographic covariance profiles unique to neurodegenerative disorders such as
      Parkinson's Disease at various stages of progression. Each profile represents a
      neuroanatomical network of metabolically covarying regions. The expression of the
      profile in each patient is characterized by a subject score which can correlate
      with independent clinical disease severity measures. To visualize these profiles,
      a semi-automatic routine is used (3D) animation of the metabolic topography as it
      evolves from initial to final stages of the disease.

PMID- 7641175
TI  - Unilateral cerebral cortical and basal ganglia enhancement following overdosage
      of nonionic contrast media.
AB  - A 69-year-old woman developed seizures after cerebral angiography immediately
      preceded by coronary angiography. The preceding coronary angiography resulted in
      hyperconcentration, hyperosmolar loading, and overdosing of the nonionic contrast
      medium. A CT examination demonstrated gyriform enhancement throughout the left
      cortex and the left basal ganglia. Preloading with contrast material, as in this
      case, predisposes to disruption of the blood-brain barrier during selective
      common carotid or vertebral artery injection with nonionic contrast.

PMID- 7641176
TI  - Incorporation of 5-bromo-2'-deoxyuridine into colorectal liver metastases and
      liver in patients receiving a 7-day hepatic arterial infusion.
AB  - Preclinical and clinical data suggest that the combination of hepatic arterial
      bromodeoxyuridine (BrdUrd), a thymidine analogue radiation sensitizer, and high
      dose three-dimensional conformal radiation therapy offer a high potential for
      improving the local control of intrahepatic cancers. A key step in the design of
      a successful protocol is to determine in patients the conditions for BrdUrd
      administration that would be expected to produce selective radiosensitization of
      the tumor. Therefore, we designed a clinical trial to assess BrdUrd incorporation
      into the DNA of hepatic colorectal metastases and normal liver after a 7-day
      continuous BrdUrd infusion at a dose rate of 25 mg/kg/day (the maximal tolerated
      dose for a 14-day infusion) for patients undergoing laparotomy for either
      resection of liver metastases or hepatic arterial catheter and pump placement.
      Thirteen patients were entered into this study. We found that the average
      replacement of thymidine by BrdUrd in the tumor and normal liver were 11.6 +/-
      1.2% and 1.1 +/- 0.2%, respectively. This extent of incorporation would be
      expected to produce a single fraction radiation enhancement of 1.5 in the tumor
      without detectable sensitization of the normal liver. Immunohistochemical
      staining for BrdUrd revealed heterogeneity of incorporation with a range of
      approximately 60-80% of the cells labeled in different regions of the specimens.
      These findings suggest that hepatic arterial BrdUrd given at this dose and
      schedule has a high likelihood of producing clinically significant
      radiosensitization for patients with hepatic metastases from colorectal cancer.
      Furthermore, the demonstrated selectivity of tumor perfusion that can be obtained
      with hepatic arterial infusion combined with the high proliferative rate of
      colorectal metastases (versus normal liver) suggests that these patients may be
      good candidates for tumor-directed gene transfer therapy by using regionally
      delivered retroviral vectors.

PMID- 7641177
TI  - Interleukin 4 retards dissemination of a human B-cell lymphoma in severe combined
      immunodeficient mice.
AB  - We have examined the antitumor activity of murine interleukin 4 (IL-4) on
      development of a human B-cell lymphoma (Daudi) in severe combined immunodeficient
      (SCID) mice. The progression of Daudi cells in SCID mice was followed by
      histological staining and by flow cytometric analysis of CD20+ cells in spleen,
      liver, bone marrow, and kidneys. By day 35, CD20+ Daudi cells populate the
      majority of space in the bone marrow and kidney in vehicle-treated mice. Mice
      receiving i.p. injections of IL-4, commencing 7 or 14 days after tumor
      inoculation, exhibit a reduction in tumor burden as well as a decrease in CD20+
      cells in both compartments. The antitumor activity of IL-4 does not appear to be
      due to an antiproliferative effect, since the cytokine does not alter the growth
      of Daudi cells in vitro, nor does it correlate with any marked cellular
      infiltrate in tumor-bearing tissues. In 51Cr-release assays, we observed that
      splenocytes from IL-4-treated mice were capable of lysing YAC-1 but not Daudi
      cell targets. Our findings demonstrate that: (a) systemic administration of IL-4
      retards dissemination of a human B-cell lymphoma in SCID mice; and (b) antitumor
      activity elicited by IL-4 may not involve a direct effect on proliferation of
      Daudi cells or on the induction of cytolytic activity.

PMID- 7641178
TI  - Involvement of NAD-poly(ADP-ribose) metabolism in p53 regulation and its
      consequences.
AB  - We have used two different approaches to study the consequences of NAD/poly(ADP
      ribose) deficiency on p53 expression and its activity in V79-derived cell lines.
      In the first approach, we have used two cell lines that are deficient in poly(ADP
      ribose) (pADPR) synthesis because of deficiency in the enzyme poly(ADP-ribose)
      polymerase (PARP). In a second approach, we have used a cell line that is
      deficient in NAD/pADPR metabolism due to unavailability of NAD, the substrate for
      PARP. These NAD/PARP-deficient cell lines exhibit a significant reduction in both
      baseline p53 expression and its activity compared to their parental V79 cells.
      Furthermore, etoposide, a topoisomerase II inhibitor that was shown to cause an
      increase in p53 expression and subsequent apoptosis in V79 cells, failed to
      produce any significant increase in p53 expression or apoptotic DNA fragmentation
      in NAD/PARP-deficient cell lines. Thus, our studies suggest that NAD/pADPR
      synthesis may be involved in the regulation of p53 and its dependent pathways.

PMID- 7641179
TI  - In vivo administration of dichloroacetic acid suppresses spontaneous apoptosis in
      murine hepatocytes.
AB  - Spontaneous apoptosis in hepatocytes of male B6C3F1 mice that received
      dichloroacetic acid (DCA) in their drinking water for 5-30 days (28-58 days of
      life) was examined as part of ongoing studies to determine the molecular basis of
      the hepatocarcinogenicity of this nongenotoxic water chlorination by-product. DCA
      at 0.5 and 5.0 g/liter, significantly reduced apoptosis relative to untreated
      controls in a dose-dependent fashion. Regression analysis indicated that
      apoptosis declined over the 30-day period in the livers of control, age-paired
      animals receiving no drug. Animals receiving low-dose DCA exhibited a similar,
      although quantitatively depressed, trend line, whereas animals receiving high
      dose DCA showed maximal depression of apoptosis at 5 days, which was sustained
      throughout the course of the 30-day period. These studies suggest that DCA has
      the ability to down-regulate apoptosis in murine liver. When taken together with
      previous data demonstrating DCA-dependent decrease in labeling index in these
      same livers, these data further support the hypothesis that the carcinogenic
      mechanism of DCA may involve suppression of the ability of the liver to remove
      initiated cells by apoptosis rather than by induction of selective proliferation
      of initiated cells.

PMID- 7641181
TI  - Induction of apoptosis by beta-lapachone in human prostate cancer cells.
AB  - beta-Lapachone, a plant product, has been shown to be a novel inhibitor of DNA
      topoisomerase I, with a mode of action different from camptothecin and a chemical
      structure distinct from those of current anti-cancer drugs. We observed that beta
      lapachone, at concentrations of less than 8 microM, induces cell death with
      characteristics of apoptosis in human prostate cancer cell lines. This effect of
      beta-lapachone was also observed in a human promyelocytic leukemia cell line (HL
      60). beta-Lapachone-induced apoptosis is independent of p53 expression, and
      ectopic overexpression of bcl-2 did not confer significant resistance to beta
      lapachone. Among other human carcinoma and adenoma cell lines tested, human
      breast and ovary carcinoma showed sensitivity to the cytotoxic effect of beta
      lapachone without manifesting signs of apoptosis. These results suggest that beta
      lapachone is a potential compound to be added to cancer chemotherapy,
      particularly for prostate cancer.

PMID- 7641180
TI  - Beta-lapachone-mediated apoptosis in human promyelocytic leukemia (HL-60) and
      human prostate cancer cells: a p53-independent response.
AB  - beta-Lapachone and certain of its derivatives directly bind and inhibit
      topoisomerase I (Topo I) DNA unwinding activity and form DNA-Topo I complexes,
      which are not resolvable by SDS-K+ assays. We show that beta-lapachone can induce
      apoptosis in certain cells, such as in human promyelocytic leukemia (HL-60) and
      human prostate cancer (DU-145, PC-3, and LNCaP) cells, as also described by Li et
      al. (Cancer Res., 55: 0000-0000, 1995). Characteristic 180-200-bp oligonucleosome
      DNA laddering and fragmented DNA-containing apoptotic cells via flow cytometry
      and morphological examinations were observed in 4 h in HL-60 cells after a 4-h, >
      or = 0.5 microM beta-lapachone exposure. HL-60 cells treated with camptothecin or
      topotecan resulted in greater apoptotic DNA laddering and apoptotic cell
      populations than comparable equitoxic concentrations of beta-lapachone, although
      beta-lapachone was a more effective Topo I inhibitor. beta-Lapachone treatment (4
      h, 1-5 microM) resulted in a block at G0/G1, with decreases in S and G2/M phases
      and increases in apoptotic cell populations over time in HL-60 and three separate
      human prostate cancer (DU-145, PC-3, and LNCaP) cells. Similar treatments with
      topotecan or camptothecin (4 h, 1-5 microM) resulted in blockage of cells in S
      and apoptosis. Thus, beta-lapachone causes a block in G0/G1 of the cell cycle and
      induces apoptosis in cells before, or at early times during, DNA synthesis. These
      events are p53 independent, since PC-3 and HL-60 cells are null cells, LNCaP are
      wild-type, and DU-145 contain mutant p53, yet all undergo apoptosis after beta
      lapachone treatment. Interestingly, beta-lapachone treatment of p53 wild type
      containing prostate cancer cells (i.e., LNCaP) did not result in the induction of
      nuclear levels of p53 protein, as did camptothecin-treated cells. Like other Topo
      I inhibitors, beta-lapachone may induce apoptosis by locking Topo I onto DNA,
      blocking replication fork movement, and inducing apoptosis in a p53-independent
      fashion. beta-Lapachone and its derivatives, as well as other Topo I inhibitors,
      have potential clinical utility alone against human leukemia and prostate
      cancers.

PMID- 7641182
TI  - Inhibition of leukemic cell growth by the protein kinase C activator bryostatin 1
      correlates with the dephosphorylation of cyclin-dependent kinase 2.
AB  - Bryostatin 1 is a natural antineoplastic agent that activates protein kinase C.
      Treatment of U937 human leukemic cells with bryostatin 1 caused a 60% reduction
      in cell growth, whereas another protein kinase C activator, phorbol myristate
      acetate (PMA), completely inhibited U937 cell growth. Both bryostatin 1 and PMA
      induced inhibition of cyclin-dependent kinase 2 (cdk2) activity. The first phase
      of cdk2 inhibition correlated with the transient induction of p21, a known
      inhibitor of cdk2. In contrast, the second phase of cdk2 inhibition correlated
      with the dephosphorylation of cdk2 on threonine-160, which must be phosphorylated
      for cdk2 activity. The level of growth inhibition induced by these two compounds
      correlated with the degree of cdk2 dephosphorylation as follows: bryostatin 1,
      60%; PMA, 100%.

PMID- 7641183
TI  - Evidence for a connection between the mismatch repair system and the G2 cell
      cycle checkpoint.
AB  - The human colon tumor cell line HCT116 is deficient in wild-type hMLH1, is
      defective in mismatch repair (MMR), exhibits microsatellite instability, and is
      tolerant to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Transferring a normal
      copy of hMLH1 on chromosome 3 into the cell line restores MMR activity,
      stabilizes microsatellite loci, and increases the sensitivity of the cell to
      MNNG. Previous studies in other cell lines tolerant to alkylating agents such as
      MNNG or N-methylnitrosourea have shown cross-tolerance to 6-thioguanine (6TG),
      leading to a hypothesis that tolerance to MNNG or 6TG may be the result of MMR
      deficiency. To test this hypothesis, we studied the effects of 6TG on the MNNG
      tolerant, MMR-deficient HCT116 cell line and its MNNG-sensitive, MMR-proficient,
      MNNG-tolerant, and MMR-deficient derivatives. Continuous exposure to low doses of
      6TG (0.31-1.25 micrograms/ml) had no apparent effect on colony-forming ability
      (CFA) in MNNG-tolerant, MMR-deficient cells, whereas MNNG-sensitive, MMR
      proficient cells exhibited a dose-dependent decrease in CFA. Growth kinetics and
      cell cycle analysis revealed that the growth of 6TG-treated HCT116 + chr3 cells
      was arrested at G2 after exposure to low dose of 6TG. In contrast, the same
      exposure to 6TG did not induce G2 arrest but rather a G1 delay in HCT116 and
      HCT116 + chr2. To obtain further evidence for the role of MMR on 6TG and MNNG
      toxicity, we isolated an MNNG-resistant revertant clone, M2, from the MNNG
      sensitive, MMR-proficient HCT116 + chr3 cell line and characterized the MMR
      activity, hMLH1 status, and 6TG response. The results showed that M2 cells lost
      MMR activity as well as the previously introduced normal hMLH1 gene. Restoration
      of the CFA of M2 and an absence of G2 arrest were observed after treatment with
      low doses of 6TG. These results suggest that the mismatch repair system interacts
      with the G2 checkpoint in response to 6TG or MNNG-induced DNA lesions. The
      results further suggest that any agent that induces DNA mispairs will cause G2
      arrest in MMR-proficient cells but not in MMR-deficient cells.

PMID- 7641184
TI  - Alternatively spliced adenomatous polyposis coli (APC) gene transcripts that
      delete exons mutated in attenuated APC.
AB  - Reverse transcription-PCR combined with either (a) restriction enzyme digestion
      and repeat PCR or (b) ligase chain reaction has identified two new alternatively
      spliced transcripts of the adenomatous polyposis coli (APC) gene. In one of these
      transcripts exons 1-4 and the first 16 bases of exon 5 are deleted; in the other
      exons 2-4 and the first 16 bases of 5 are deleted. Both transcripts use an
      intraexonic splice acceptor in exon 5. These transcripts delete exons mutated in
      attenuated APC (3 and 4) and could account for the reduction in severity of this
      variant.

PMID- 7641185
TI  - Correlation between apoptosis, tumorigenesis, and levels of insulin-like growth
      factor I receptors.
AB  - We have investigated whether there is a quantitative relationship between the
      insulin-like growth factor I receptor (IGF-IR), the extent of apoptosis in vivo,
      and tumorigenesis. C6 rat glioblastoma cells were treated with increasing
      concentrations of antisense oligodeoxynucleotides to the IGF-IR RNA. The extent
      of apoptosis in vivo is correlated to the decrease in IGF-IR levels and, in turn,
      tumorigenesis in nude mice is correlated to the fraction of surviving cells. In
      syngeneic rats, a host response leads to complete inhibition of tumorigenesis.
      These findings establish, for the first time on a quantitative basis, the
      relationship between IGF-IR levels and the extent of apoptosis, as well as the
      relationship between the initial apoptotic event and the time of appearance of
      transplantable tumors.

PMID- 7641186
TI  - Base excision repair of U:G mismatches at a mutational hotspot in the p53 gene is
      more efficient than base excision repair of T:G mismatches in extracts of human
      colon tumors.
AB  - Approximately 50% of mutations that inactivate the p53 tumor suppressor gene in
      the germline and in colon tumors are C to T transitions at methylation sites (CpG
      sites). These mutations are believed to be caused by an endogenous mechanism and
      spontaneous deamination of 5-methyl-cytosine to T is likely to contribute
      significantly to this high mutation rate. The resulting T:G mismatches created by
      this process have been hypothesized to be less efficiently repaired than U:G
      mismatches formed by deamination of C. We have, therefore, performed the first
      study to directly compare rates of T:G versus U:G base excision repair at
      identical sites observed to be mutated in the p53 gene using extracts of human
      normal colon mucosa and colon carcinoma tissue. Mismatched U was excised up to
      6000-fold more efficiently than T, suggesting that differences in repair
      efficiencies are the major source of C to T transition mutations at CpG sites in
      human tissues. The data also suggests that T:G mismatches are repaired by
      additional mechanisms in human cells.

PMID- 7641187
TI  - Human breast carcinoma cells transfected with the gene encoding a c-myc promoter
      binding protein (MBP-1) inhibits tumors in nude mice.
AB  - We have identified previously a gene from a human cervical carcinoma cell (HeLa)
      cDNA expression library that encodes a M(r) approximately 37,000 c-myc promoter
      binding protein (MBP-1), which binds to the TATA box sequences of c-myc P2
      promoter and exerts a negative regulatory function by down-regulating c-myc
      expression. In normal human tissues, this cloned gene showed variable expression.
      In this study, we have demonstrated that introduction of the MBP-1 gene into
      human breast carcinoma cells reduced their ability to invade through a basement
      membrane matrix in vitro but did not alter their growth rate. Human breast
      carcinoma transfected with MBP-1 cells showed a loss of anchorage-independent
      growth and also suppressed tumor formation in athymic nude mice. These results
      suggest the possible involvement of MBP-1 as a tumor suppressor gene in human
      breast carcinoma cells.

PMID- 7641188
TI  - Vascular permeability in a human tumor xenograft: molecular size dependence and
      cutoff size.
AB  - Molecular size is one of the key determinants of transvascular transport of
      therapeutic agents in tumors. However, there are no data in the literature on the
      molecular size dependence of microvascular permeability in tumors. Therefore, we
      measured microvascular permeability to various macromolecules in the human colon
      adenocarcinoma LS174T transplanted in dorsal skin chambers in severe combined
      immunodeficient mice. These molecules were fluorescently labeled and injected
      i.v. into mice. The microvascular permeability was calculated from the
      fluorescence intensity measured by the intravital fluorescence microscopy
      technique. The value of permeability varied approximately 2-fold in the range of
      molecular weight from 25,000 to 160,000. These data indicate that tumor vessels
      are less permselective than normal vessels, presumably due to large pores in the
      vessel wall. The transport of macromolecules appears to be limited by diffusion
      through these pores. The cutoff size of the pores was estimated by observations
      of transvascular transport of sterically stabilized liposomes of 100-600 nm in
      diameter. We found that tumor vessels in our model were permeable to liposomes of
      up to 400 nm in diameter, suggesting that the cutoff size of the pores is between
      400 and 600 nm in diameter.

PMID- 7641190
TI  - Cell proliferation as a major risk factor for cancer: a concept of doubtful
      validity.

PMID- 7641189
TI  - A CYP1A1 restriction fragment length polymorphism is associated with breast
      cancer in African-American women.
AB  - We examined the role of CYP1A1 polymorphisms as potential molecular markers of
      breast cancer susceptibility in Caucasian and African-American women. The case
      control study involved 51 women with breast cancer and 269 female controls. In
      African-Americans, the frequency of the homozygous MspI polymorphism was 3.5% in
      controls and 19% in breast cancer cases. The odds ratio of breast cancer with the
      MspI homozygous variant was 9.7 (95% confidence interval: 2.0-47.9). This
      association was not observed in Caucasian women. The exon 7 and AA polymorphisms
      were not associated with breast cancer in either group. The mechanism for the
      observed association between the MspI polymorphism and breast cancer is unclear.
      It is possible that the CYP1A1 MspI RFLP is linked with other polymorphisms in
      the African-American population, either in the CYP1A1 gene, which is involved in
      estrogen metabolism, or other genes related to risk of breast cancer.

PMID- 7641191
TI  - Influence of cellular trafficking on protein synthesis inhibition of immunotoxins
      directed against the transferrin receptor.
AB  - Previously, a quantitative analysis that related protein synthesis inhibition of
      transferrin-toxin conjugates to the cellular trafficking of transferrin was
      proposed (P.T. Yazdi and R. M. Murphy, Cancer Res., 54: 6387-6394, 1994). Here,
      this work is extended to evaluate cellular trafficking of anti-transferrin
      receptor antibodies and protein synthesis inhibition kinetics of immunotoxins
      constructed from the same antibodies and the toxin gelonin. Cellular trafficking
      models for two monoclonal anti-transferrin receptor antibodies (5E9 and OKT9) in
      HeLa cells were developed. The two mAbs had similar trafficking parameters, which
      differed significantly from those for transferrin. Protein synthesis inhibition
      kinetics for immunotoxins constructed from 5E9 or OKT9 and gelonin were measured.
      Analysis of the data using our previously proposed relationship between protein
      synthesis and cellular trafficking indicated that the relationship is also valid
      for these new systems. The protein synthesis inhibition constants for 5E9-gelonin
      and OKT9-gelonin conjugates were similar to those for the transferrin-gelonin
      conjugate. These results suggest that it may be possible to predict the efficacy
      of gelonin immunotoxins from knowledge of the trafficking of the corresponding
      targeting agent. A sensitivity analysis showed which cellular trafficking
      parameters have the greatest influence on immunotoxin efficacy and are,
      therefore, the most likely to be profitably manipulated.

PMID- 7641192
TI  - Reduced fidelity of DNA synthesis in cell extracts from chemically induced
      primary thymic lymphomas of mice.
AB  - To examine whether the fidelity of DNA synthesis is reduced in tumor cells, M13
      mp2-based fidelity assays were carried out using 15 samples of whole-cell
      extracts from primary mouse thymic lymphomas induced by alkylating agents. We
      found that DNA synthesis activities of thymic lymphomas, detected as
      incorporation of [3H]TTP into acid-insoluble materials, were 2- to 10-fold higher
      compared to those of normal thymus. Furthermore, mutant frequencies in the
      forward mutation assay of DNA synthesis were increased 2- to 7-fold in cell
      extracts from thymic lymphomas compared to those from normal thymus. As the DNA
      polymerase beta (pol beta) activity was extremely high in the thymic lymphomas,
      we screened mutations in the pol beta gene to examine the possibility of
      involvement of mutated pol beta in reduction of the fidelity of DNA synthesis. Of
      20 lymphomas, one case of point mutation (T to A) was found by reverse
      transcription-PCR single-strand conformation polymorphism analysis. These results
      suggest that the mutagenic DNA synthesis is involved in murine thymic lymphoma
      genesis, although mutation of the pol beta gene is not a major causal event.

PMID- 7641193
TI  - Frequent development of pancreatic carcinomas in the Rana nigromaculata group.
AB  - In 1979, 2 species of pond frogs (Rana nigromaculata and Rana plancyi plancyi)
      were imported from China, and hybrids were made between these and Japanese,
      Korean, and Taiwanese pond frogs (R. nigromaculata, Rana plancyi fukienensis and
      Rana brevipoda) that had been kept for a number of years in the Laboratory for
      Amphibian Biology of Hiroshima University. From 1982, development of tumors,
      especially in the peritoneal cavity, was noticed frequently in the hybrids and
      also later, although rarely, in the Japanese pond frogs. Such tumors had never
      previously been observed among pond frogs in the laboratory. Histological and
      immunohistochemical studies identified the i.p. tumors to be pancreatic
      carcinomas with occasional production of insulin and/or somatostatin.
      Ultrastructural investigation revealed both endocrine and exocrine secretion
      granules together with C-type retrovirus particles in the carcinoma cells. Other
      tumors included a retroperitoneal rhabdomyosarcoma, liver adenomas, and an
      unclassifiable mesenchymal tumor of the foot pad.

PMID- 7641194
TI  - Expression of cyclooxygenase-1 and -2 in human colorectal cancer.
AB  - Several studies indicate that nonsteroidal anti-inflammatory drugs including
      indomethacin, aspirin, sulindac, and piroxicam reduce the risk of colon cancer.
      Furthermore, nonsteroidal anti-inflammatory drugs that inhibit the cyclooxygenase
      (COX) enzyme were shown to inhibit the development of colon cancer in animal
      models of carcinogenesis. Non-steroidal anti-inflammatory drugs inhibit the
      enzymatic activity of both the constitutive (COX-1) and inducible (COX-2)
      isoforms of COX enzyme. We have investigated the expression of COX-1 and COX-2
      polypeptides in human colon cancer tissues using immunohistochemistry. Enhanced
      COX-2 expression was observed in colon cancer tissues from 15 subjects with
      clinically diagnosed colorectal cancer. Marked COX-2 expression was observed in
      cancer cells, inflammatory cells, vascular endothelium, and fibroblasts of the
      lesional tissues compared with the nonlesional and normal colon tissues. The
      extent and intensity of the immunoreactive COX-2 in cancer cells was much greater
      than that of the other cell types. In contrast, the expression of COX-1
      polypeptide was weak in both normal and cancerous specimens. These data suggest
      that the enhanced expression of the COX-2 gene in colon cancer tissues may
      contribute to the enhanced synthesis of prostaglandin E2 by the colon cancer
      tissues. Enhanced expression of COX-2 may play a role in the pathogenesis of
      colon cancer. Furthermore, selective inhibition of COX-2 may prove to be more
      efficacious in the retardation of colon cancer development.

PMID- 7641195
TI  - Isolation of a gene encoding a human reduced folate carrier (RFC1) and analysis
      of its expression in transport-deficient, methotrexate-resistant human breast
      cancer cells.
AB  - Our laboratory has previously reported the isolation of a murine cDNA which
      restores reduced folate carrier (RFC) activity and methotrexate (MTX) sensitivity
      to a MTX-resistant, transport-deficient human breast cancer cell line (MTXR ZR-75
      1) (K. H. Dixon et al., J. Biol. Chem., 269: 17-20, 1994). Using this murine cDNA
      as a probe, we have isolated two homologous overlapping partial cDNAs from a
      human testis cDNA library. In addition, using human cDNA as a probe, we have
      isolated a 20-kb human genomic fragment which contains RFC coding regions.
      Analysis of the nucleotide sequence of these clones revealed that the human RFC
      gene, RFC1, is approximately 65% homologous to the murine and hamster genes.
      Using a human genomic P1 plasmid clone containing RFC1, we mapped the location of
      RFC1 by fluorescence in situ hybridization to the end of the long arm of
      chromosome 21 (21q22.2-q22.3). Fluorescence in situ hybridization analysis also
      showed that two copies of RFC1 were present in MTXR ZR-75-1 cells, and showed no
      evidence of rearrangement of this gene. Northern blot analysis of MTXR ZR-75-1
      cells demonstrated a marked decrease in the level of the 3-kb RFC1 transcript
      relative to the parental cell line, and Western blot analysis using a polyclonal
      antibody raised against a peptide generated from the RFC1 sequence showed
      decreased expression of an approximately M(r) 56,000 protein in MTXR ZR-75-1
      cells. Finally, MTXR ZR-75-1 cells transfected with an RFC1 gene showed increased
      MTX uptake, which was more sensitive to competition by folinic acid than by folic
      acid. Therefore, decreased RFC1 expression appears to be the molecular mechanism
      of decreased MTX uptake in this MTX-resistant cell line.

PMID- 7641196
TI  - Functional activity of the reduced folate carrier in KB, MA104, and IGROV-I cells
      expressing folate-binding protein.
AB  - The role of a membrane-associated folate binding protein (mFBP) in transport of
      folate analogues was investigated in three epithelial cell lines that were grown
      in high folate medium and folate-conditioned medium and express different levels
      of mFBP: human nasopharyngeal KB cells, monkey kidney MA104 cells, and IGROV-I
      ovarian carcinoma cells. Folate analogues were selected for which mFBP exhibits a
      low affinity, i.e., methotrexate (MTX) and 10-ethyl-10-deazaaminopterin (10-EdAM)
      or a (moderately) high affinity as compared to folic acid, i.e., N-(5[N-(3,4
      dihydro-2-methyl-4-oxoquinazolin-6-ylmethyl(-N-m ethylamino]-2-theonyl)-L
      glutamic acid (ZD1694), N10-propargyl-5,8-dideazafolic acid (CB3717), and 5,10
      dideazatetrahydrofolic acid. Regardless of the medium folate status, growth
      inhibition studies with IGROV-I and MA104 cells demonstrated a lack of
      correlation between the affinity of mFBP for the antifolate drugs and their
      sensitivity profile; both cell lines were highly sensitive to growth inhibition
      by MTX, 10-EdAM, ZD1694 and 5,10-dideazatetrahydrofolic acid, but were
      insensitive for CB3717. The same drug sensitivity profile was observed for KB
      cells, with the exception that these cells were also sensitive to growth
      inhibition by CB3717 but only in folate-conditioned medium. This overall drug
      sensitivity profile appeared to correlate with the differential efficiency of
      drug transport via the "classical" reduced folate/MTX carrier (RFC), rather than
      by mFBP. Characteristics that further supported functional RFC activity in KB,
      IGROV-I, and MA104 cells included: (a) the growth inhibitory effects of the drugs
      could be prevented by the reduced folate leucovorin rather than by folic acid;
      (b) rates for uptake of [3H]10-EdAM were 2-4-fold higher than for [3H]MTX at 1
      microM extracellular concentrations and coincided with the affinity of the RFC
      for these drugs, rather than those of the mFBP; (c) uptake of [3H]10-EdAM and
      [3H]leucovorin was markedly inhibited by leucovorin and 10-EdAM, respectively, or
      by an N-hydroxysuccinimide ester of MTX (irreversibly labeling RFC) but only to a
      minor extent by folic acid or an N-hydroxysuccinimide ester of folic acid
      (irreversibly labeling mFBP); and, finally, (d) labeling with an N
      hydroxysuccinimide ester of [3H]MTX identified a protein with a molecular weight
      within the range of that reported for the RFC in human leukemic cells.
      Altogether, these results indicate that both RFC and mFBP are coexpressed in
      three epithelial cell lines and that RFC is the preferential route of entry for
      antifolate compounds, even when mFBP is expressed to very high levels.

PMID- 7641197
TI  - Intraarterial administration of melphalan for treatment of intracranial human
      glioma xenografts in athymic rats.
AB  - Malignant gliomas will affect 15,000-17,000 Americans each year and carry a
      dismal prognosis. Adjuvant chemotherapy is hampered by inadequate drug delivery,
      systemic toxicity, and a markedly variable biological sensitivity. Intraarterial
      (i.a.) therapy may enhance selectivity by improving tumor drug delivery and
      reducing systemic toxicity. Using melphalan given i.a., we studied the therapy of
      intracranial human glioma xenografts in male athymic nude rats (mean weight, 300
      g) which were inoculated intracerebrally with D-54 MG and D-456 MG. On Days 6 and
      7 (D-54 MG) or Days 9 and 10 (D-456 MG), rats randomized by body weight and
      treated with single-dose melphalan given i.a. at 0.5 or 0.75 mg produced
      significantly higher median survival (D-54 MG, Days 33 and 32; D-456 MG, Days 52
      and 54, respectively) compared with i.a. saline (D-54 MG, Day 14, P < 0.001; D
      456 MG, Day 24, P = 0.000) or melphalan given i.v. at 0.75 mg and 0.9 mg (D-54 MG
      only; Day 19, P < 0.001; Day 23, P < 0.001, respectively) and at 0.5 and 0.75 mg
      (D-456 MG only; Day 26 for both doses, P = 0.00). Although a dose-dependent
      increase in median survival (D-54 MG, 0.25 mg, Day 18; 0.5 mg, Day 28.5; 0.75 mg,
      Day 32.5) was observed with i.a. administered melphalan, no significant
      difference was apparent between 0.5 and 0.75 mg in either tumor model (D-54 MG, P
      = 0.15; D-456 MG, P = 0.37). Toxicity studies in nontumor-bearing athymic rats
      yielded a maximum tolerated dose of 0.8 mg for i.a. administered melphalan. This
      dosage was superior in spite of different xenograft permeabilities (apparent mean
      blood-to-tissue transport [K] values for alpha-aminoisobutyric acid, 5.8 for D-54
      MG and 1.3 for D-456 MG). Pharmacokinetic experiments demonstrated a significant
      first pass advantage for i.a. (versus i.v.) melphalan. The short plasma half
      life, marked antiglioma activity, and lack of requirement for metabolic
      activation indicate that i.a. melphalan holds considerable promise for human
      glioma therapy.

PMID- 7641198
TI  - Liposome-mediated in vivo gene transfer of antisense K-ras construct inhibits
      pancreatic tumor dissemination in the murine peritoneal cavity.
AB  - K-ras point mutation occurs at a characteristically high incidence in human
      pancreatic cancer. Plasmids expressing antisense (AS), AS-K-ras-LNSX or sense K
      ras gene fragment, were first transduced into three human pancreatic cancer cell
      lines (AsPC-1, MIAPaCa-2, and BxPC-3) by liposome-mediated transfection. A stable
      expression of antisense or sense K-ras RNA was detected by Northern blot
      analysis, and Western blot analysis confirmed a reduction of up to 20% of K-ras
      specific p21 protein in AsPC-1 cells transduced with AS-K-ras-LNSX. The growth of
      pancreatic cancer cells with K-ras point mutations (AsPC-1 and MIAPaCa-2) was
      significantly suppressed after transduction of AS-K-ras-LNSX, although the effect
      of antisense construct was not found in cells with a wild-type K-ras gene (BxPC
      3). Next, to test the efficacy in vivo, AsPC-1 cells were inoculated into the
      intraperitoneal cavity of nude mice, and 3 days later, the AS-K-ras-LNSX:liposome
      complex was injected i.p. 3 times. Twenty-eight days after tumor cell
      inoculation, 9 of 10 control mice developed peritoneal dissemination and/or solid
      tumors on the pancreas, whereas only 2 of 12 mice treated with AS-K-ras-LNSX
      showed any evidence of tumors. Although PCR analysis indicated that the injected
      DNA was delivered to various organs except for the brain, treatment-related
      toxicity was not observed. This study shows that the liposome-mediated in vivo
      gene transfer of antisense K-ras construct may be a useful therapeutic strategy
      for pancreatic cancer.

PMID- 7641199
TI  - Inhibition of lymphoma growth in vivo by combined treatment with hydroxyethyl
      starch deferoxamine conjugate and IgG monoclonal antibodies against the
      transferrin receptor.
AB  - Synergistic inhibition of hematopoietic tumor growth can be observed in vitro
      when the iron chelator deferoxamine (DFO) is used in combination with an IgG mAb
      against the anti-transferrin receptor antibody (ATRA). Our goal was to ascertain
      whether similar findings could be seen in vivo. A high molecular weight conjugate
      of deferoxamine, known as hydroxyethyl starch (HES) DFO or HES-DFO, was tested in
      conjunction with C2, a well-defined rat antimouse transferrin receptor mAb,
      against the 38C13 tumor in C3H/HeN mice. It was shown that while neither HES-DFO
      alone nor C2 alone produced consistent, significant inhibition of tumor growth,
      the combination of HES-DFO and C2 produced virtually complete inhibition of
      initial tumor outgrowth. The latter combination failed, however, to inhibit the
      growth of established tumors. It was then found that when C2 was used in
      conjunction with RL34, another IgG ATRA, the two ATRAS were themselves capable of
      causing synergistic inhibition of the growth of 38C13 in vitro. When the two IgG
      ATRAS were used together in vivo, regressions of established tumors were
      observed. Moreover, the addition of HES-DFO to the IgG ATRA pair then caused more
      frequent regressions. Although there was never any obvious toxicity seen with a
      single IgG ATRA, the use of the IgG ATRA pair was associated with sporadic
      mortality. In addition, although HES-DFO by itself was also not associated with
      any obvious toxicity, combined treatment with HES-DFO and a single ATRA resulted
      in death due to bacterial infection in about half of the mice after 10-15 days.
      Combined treatment with HES-DFO and the ATRA pair resulted in death attributed to
      infection in nearly all of the mice after 6 days. Thus, an iron deprivation
      treatment protocol with HES-DFO and IgG ATRAS produced both a significant
      antitumor effect and an increased risk of infection in a murine model system.

PMID- 7641200
TI  - Reduction of the renal uptake of radiolabeled monoclonal antibody fragments by
      cationic amino acids and their derivatives.
AB  - The renal uptake of radiolabeled antibody fragments and peptides is a problem in
      radioimmunodetection and radioimmunotherapy, especially with intracellular
      retained radiometals. The aim of this study was to develop suitable methods to
      reduce this kidney uptake. BALB/c mice or nude mice bearing the human GW-39 colon
      carcinoma xenograft were given i.p. injections of basic amino acids or a range of
      different basic amino acid derivatives, amino sugars, as well as cationic
      peptides. The effect of these agents on the biodistribution of Fab' and F(ab')2
      fragments of different mAbs radiolabeled with 99mTc, 188Re, 111In, 88Y, or 125I
      was studied. Tumor and organ uptake was determined and compared to untreated
      mice. The kidney uptake of Fab' fragments was reduced 5-6-fold in a dose
      dependent manner as compared to untreated controls. The uptake in all other
      organs, as well as the tumor, was unaffected. A similar reduction in renal
      retention was seen for all other intracellularly retained isotopes, as well as
      for F(ab')2 fragments. D- and L-isomers of lysine were equally effective whether
      given i.p. or p.o. D-glucosamine was effective, but its N-acetyl derivative was
      not. Basic polypeptides (e.g., poly-L-lysine) were also effective; their potency
      increased with increasing molecular weight. HPLC of the urine taken from treated
      animals showed the excretion of intact Fab', in contrast to mostly low-molecular
      weight metabolites in the control group. These studies indicate that a variety of
      basic compounds is capable of inhibiting the tubular reabsorption of peptides and
      proteins, thus lowering the kidney uptake of antibody fragments significantly. On
      a molecular basis, the effect seems to essentially rely on the presence of a
      positively charged amino group. By reducing renal retention of antibody
      fragments, their role as imaging and therapeutic agents may be expanded.

PMID- 7641201
TI  - Identification of HLA-unrestricted CD8+/CD28- cytotoxic T-cell clones specific
      for leukemic blasts in children with acute leukemia.
AB  - We report on the identification of 57 T-cell clones (TCC) cytolytic to autologous
      leukemic blasts (LB) but not autologous bone marrow remission cells. LB-reactive
      TCC were obtained from 3 children with acute leukemia at remission; all expressed
      the same phenotype, CD3/TCR alpha beta/CD8+, but were heterogeneous for the
      expression of V beta T-cell receptor (TCR) V region chains, thus showing that
      these cells were not derived from the expansion of a single clone. Cytolytic
      activity of LB-reactive TCC was not restricted to autologous LB because they were
      also able to lyse phenotypically similar allogeneic LB but not bone marrow
      remission cells of the same patients. Neither autologous nor allogeneic LB used
      in the present study as stimulator and target cells expressed CD80 (B7/BB-1)
      antigen, and LB-reactive TCC were CD28-. Cytolytic activity of the clones was
      only inhibited by anti-CD11a (LFA-1) mAb but not by mAbs specific for HLA class I
      and II, CD3, CD8, or TCR alpha beta. In conclusion, these data suggest that a
      subset of apparently HLA-unrestricted, CD3/TCR alpha beta/CD8+ CD28- cytotoxic T
      lymphocytes, which use a TCR/CD3-independent recognition pathway, is primarily
      involved in antitumor immune response of children with acute leukemia at
      remission, possibly contributing to the control of minimal residual disease.

PMID- 7641202
TI  - Partial degradation of T-cell signal transduction molecules by contaminating
      granulocytes during protein extraction of splenic T cells from tumor-bearing
      mice.
AB  - Flavone-8-acetic acid plus recombinant human interleukin 2 is a successful
      antitumor therapy in mice bearing the Renca murine renal cell carcinoma. This
      report demonstrates that T cells, particularly CD8+ T cells, are critical for the
      generation of this response. Initial experiments examining T-cell signal
      transduction proteins demonstrated that T cells from Renca-bearing mice had
      undetectable levels of p56lck and zeta-chain of the T-cell receptor and that
      flavone-8-acetic acid and recombinant human interleukin 2 therapy could be used
      as a model for reversal of these alterations. However, further experimentation
      showed that the majority of the reduction in zeta-chain and part of the reduction
      in p56lck was due to degradation of these molecules during protein extraction
      caused by mature granulocytes contaminating the enriched T-cell population. This
      was not the case for nuclear c-Rel or NF kappa B p65, which remained at
      undetectable/reduced levels in the absence of granulocytes, confirming our
      previous data that transcription factor alterations exist in tumor-bearing mice.
      Thus, most of the reduction in zeta-chain in T cells from Renca-bearing mice is
      due to granulocyte contamination and emphasizes the need to use pure T-cell
      populations and/or sufficient amounts and types of protease inhibitors when
      quantitating proteins in T cells from tumor-bearing mice.

PMID- 7641203
TI  - Human non-small cell lung cancer cells express a type 2 cytokine pattern.
AB  - In addition to infiltrating inflammatory cells, tumors also produce cytokines and
      growth factors that may alter tumor growth, tumor immunogenicity, and the host
      immune response. To characterize the expression profile of human non-small cell
      lung cancer (NSCLC)-derived cytokines, the mRNA expression of type 1 and type 2
      cytokines in five human NSCLC lines was analyzed by reverse transcriptase-PCR.
      Expression of interleukin 5 (IL-5) and IL-10 was demonstrated in all tumor lines
      evaluated, whereas IL-4 was present in three of five lines and IL-13 was present
      in two of five lines. In contrast, none of the tumor lines expressed IL-2 and IFN
      gamma. Type 2 cytokine protein production by NSCLC lines was confirmed by
      immunoprecipitation and cytokine specific ELISA. Tumor-derived IL-10 secretion
      was significantly augmented by exogenous recombinant cytokines including IL-4 and
      tumor necrosis factor-alpha. To evaluate whether fresh NSCLC nodules also express
      a type 2 cytokine pattern, the content of type 1 and type 2 cytokines in tissue
      homogenates from 13 fresh NSCLC nodules and normal lung surgical specimens was
      assessed. Human NSCLC nodules contain significantly more type 2 cytokines than
      does normal lung tissue when corrected for total protein concentration. To
      identify the cellular source of type 2 cytokine production in tumor nodules,
      immunohistology was performed on sections from 5 lung squamous cell carcinomas
      and 5 adenocarcinomas. All of the specimens revealed positive staining for type 2
      cytokines within tumor cells. In summary, we report that human NSCLC cells
      produce type 2 cytokines both in situ and in vitro, which may play an active
      immunoregulatory role in the lung cancer microenvironment.

PMID- 7641204
TI  - Multiple myeloma: high incidence of chromosomal aneuploidy as detected by
      interphase fluorescence in situ hybridization.
AB  - Because metaphase cytogenetic studies in multiple myeloma (MM) are hampered by a
      low proliferative activity of myeloma cells in vitro, interphase cytogenetics by
      means of fluorescence in situ hybridization (FISH) should improve the detection
      of chromosomal abnormalities in MM. We therefore investigated chromosomal
      aneuploidy in 36 patients with MM using interphase FISH and alpha-satellite DNA
      probes for chromosomes 1, 3, 7, 8, 11, 12, 16, 17, 18, and X. By FISH, myeloma
      cells from 32 patients (88.9%) were aneuploid for at least one of the chromosomes
      examined. In 24 patients (66%), aberrations of > or = 3 chromosomes were
      observed. Aneuploidy was predominantly characterized by a gain of chromosome
      numbers, with involvement of chromosomes 3, 7, and 11 occurring in > 50% of
      patients. Loss of a centromeric signal suggesting monosomy was most frequently
      observed for chromosomes 17 (22.2% of patients) and X (monosomic in 42.3% of
      female patients, but loss of chromosome X was never observed in males, P < 0.05).
      Dual-color FISH studies provided evidence for marked heterogeneity of aneuploid
      cells in 8 patients (22.8%). Occurrence of chromosomal aneuploidy was independent
      of stage and pretreatment status. Gain of chromosome 3 was significantly
      correlated with an IgA paraprotein (P < 0.05). In 12 patients, the direct
      comparison of metaphase cytogenetics and FISH showed that FISH detected
      aneuploidy of chromosomes in 9 patients that was missed by metaphase analysis. In
      conclusion, interphase FISH, by which chromosomal aneuploidy was detected in
      almost 90% of patients with MM, represents an approach for evaluating the
      clinical significance of specific chromosomal abnormalities in MM.

PMID- 7641205
TI  - DNA topoisomerase II alpha gene expression under transcriptional control in
      etoposide/teniposide-resistant human cancer cells.
AB  - We previously isolated etoposide/teniposide-resistant cell lines from human
      cancer KB cells, designated KB/VP-2 and KB/VM-4, respectively, and we found that
      decreased expression of topoisomerase II alpha was associated with the
      acquisition of etoposide/teniposide resistance in both resistant cell lines. In
      this study, we studied how the expression of the DNA topoisomerase II alpha gene
      is regulated in drug-resistant cell lines at the transcriptional level. We first
      examined whether the decreased topoisomerase II alpha mRNA level was due to a
      shorter lifetime of mRNA molecules in drug-resistant cell lines. A comparison of
      the degradation kinetics of topoisomerase II alpha mRNA demonstrated that there
      was no difference in mRNA stability between both resistant cell lines and their
      parental counterpart. A run-on experiment with isolated nuclei showed that the
      transcriptional activity of topoisomerase II alpha gene of both resistant cell
      lines constituted less than 20% of the parental KB cells. The activity of DNA
      topoisomerase II alpha promoter in resistant cells was also less than 20% of that
      in KB cells when transient transfection assays were performed with the promoter
      driven bacterial chloramphenicol acetyltransferase gene. Among the several
      transcription factors that might be involved in DNA topoisomerase II alpha gene
      expression, expression of Sp3, an inhibitory member of the Sp1 family, was
      elevated to about 3-fold higher in both resistant cell lines than their parental
      counterpart. These results indicated that the expression of DNA topoisomerase II
      alpha gene decreased at the transcriptional level through the enhanced expression
      of Sp3 in our two etoposide/teniposide-resistant cell lines.

PMID- 7641206
TI  - Analysis of meningiomas by methylation- and transcription-based clonality assays.
AB  - The clonal derivation of tumors can be determined by X chromosome inactivation
      analysis based on differential expression of genes or differential methylation of
      cytosine residues in CpG islands near polymorphic loci. In this report, we
      compared a transcription-based RNA analysis with a methylation-based DNA assay to
      determine clonality of meningiomas. Both clonality assays use PCR-based analysis
      at the hunan androgen-receptor gene (HUMARA) on the X chromosome. Among 23
      meningiomas from female patients, 19 were informative heterozygotes at this locus
      (83%). The patterns of X chromosome inactivation in four patients were extremely
      skewed towards one allele in blood (unequal Lyonization), which precluded
      clonality determination in the tumor samples. Concordant clonality results with
      methylation- and transcription-based clonality assays were demonstrated in 9 of
      13 informative tumors expressing the androgen receptor. Seven meningiomas were
      monoclonal, but surprisingly, two pathologically documented cases of meningiomas
      were polyclonal. There was disparity in 4 of 13 tumor specimens that were
      polyclonal by the methylation-based assay but monoclonal by the transcription
      assay. Clonality examination of these tumors by the methylation-based
      phosphoglycerate kinase assay provided identical results to the methylation-based
      analysis at the HUMARA locus. In addition, loss of heterozygosity (LOH) studies
      of chromosome 22, which is frequently deleted in meningiomas, showed that four of
      four informative samples of the six polyclonal tumors had partial LOH in tumor
      tissues. However, complete LOH was observed in primary cultured cells, which were
      also monoclonal by the methylation assay. Taken together, these data suggest that
      the disparity of the two assays in these four cases may be due to differences in
      the level of expression of the androgen receptor gene in tumors. Therefore, we
      conclude that: (a) clonal derivation of meningiomas determined by both
      transcription- and methylation-based clonality assays are in full agreement in
      many (9 of 13) but not all cases (4 of 13); and (b) most meningiomas (9 of 15)
      are monoclonal in origin, whereas some meningioma samples (6 of 15) are
      polyclonal or may contain heterogeneous components.

PMID- 7641207
TI  - In vitro and in vivo footprint analysis of the promoter of carcinoembryonic
      antigen in colon carcinoma cells: effects of interferon gamma treatment.
AB  - The analysis of the carcinoembryonic antigen (CEA) promoter in the colon
      carcinoma lines HT-29 and SW403, using HeLa as a control, was performed using gel
      mobility shift assays and in vitro and in vivo footprinting before and after IFN
      gamma treatment. Using a 332-bp probe extending from the start of translation (+1
      to -331), we detected 4-5 specific complexes that increased with intensity with
      IFN-gamma treatment as measured by a gel mobility shift assay. In contrast, no
      complexes were observed for probes covering the regions -500 to -1000 and -1000
      to -1500. DNase I in vitro footprinting with the 332-bp probe revealed three
      footprints, FP-I to FP-III, none of which changed during the course of IFN-gamma
      treatment. Using probes corresponding to each footprint, 6-7 specific complexes
      were observed by gel mobility shift assays. Although minor changes were observed
      on IFN-gamma treatment, no consistent pattern was observed for all cell lines
      tested. Several of the proteins involved in the promoter complexes were
      identified by antibody super shifts, UV cross-linking, and Southwestern blotting.
      FP-I bound an Sp1-like protein, binding to a GT box sequence, and USF (upstream
      regulatory factor). FP-II and FP-III bound Sp1, binding through the consensus
      sequence for a GC box. Lower molecular weight complexes of an unknown nature were
      observed with sequence specificity for both single- and double-stranded DNA.
      DNase I in vivo footprints confirmed the boundaries of FP-I to FP-III and
      revealed a fourth but weaker footprint, FP-IV. The strongest in vivo footprints
      were observed for SW403 cells, with weaker and no footprints observed for HeLa
      cells, thus correlating with the degree of CEA transcriptional activity (HeLa
      cells make no CEA mRNA). DNase I hypersensitive sites correlated well with the
      boundaries of the footprints and also revealed activity around the start of
      transcription (-110). The specific pattern for DNase I hypersensitivity for Sp1
      in the CEA promoter was the same as observed for the SV40 early promoter. In vivo
      footprinting with dimethyl sulfate revealed protein binding at the Sp1 consensus
      sequences in FP-II and FP-III and at the USF consensus sequence in FP-I. We
      conclude that in vivo footprinting is the most accurate predictor of the state of
      transcriptional activity of the CEA gene. It is also likely that Sp1 and USF play
      a major role in CEA transcriptional activation and that the majority of IFN-gamma
      effects are at the posttranscriptional level.

PMID- 7641208
TI  - Spontaneous and ionizing radiation-induced chromosomal abnormalities in p53
      deficient mice.
AB  - Chromosomal abnormalities have been assessed in p53-deficient mice. The in vivo
      frequency of spontaneous stable aberrations in bone marrow cells was elevated by
      approximately 20-fold in p53 nulls and 13-fold in p53 heterozygotes compared to
      wild-type. No excessive induction of stable aberrations by gamma-irradiation was
      observed, but p53 deficiency resulted in excess radiation-induced hyperploidy (>
      10-fold wild-type frequency). No influence of p53 genotype on sister chromatid
      exchange or G2 chromatid damage was observed in mitogen-stimulated spleen cell
      cultures; however, a p53 effect on postirradiation mitotic entry was seen.
      Abnormalities in chromosome segregation and mitotic delay following irradiation
      in p53-deficient mice suggest a G2-M checkpoint role for p53 and are broadly
      consistent with data on tumorigenesis in these animals.

PMID- 7641209
TI  - The number of 5-fluoro-2'-deoxyuridine-5'-monophosphate binding sites and reduced
      folate pool in human colorectal carcinoma tissues: changes after tegafur and
      uracil treatment.
AB  - Thymidylate synthase (TS) is a target enzyme of 5-fluorouracil and is inhibited
      by 5-fluoro-dUMP (FdUMP) to form an inactive ternary complex. We investigated the
      changes in the number of FdUMP binding sites in human colorectal carcinoma
      tissues after treatment with 5-fluorouracil derivatives and also examined the
      mechanisms underlying these changes. The number of FdUMP binding sites was
      significantly increased in patients who received tegafur and uracil
      preoperatively [UFT (+) group, n = 14] compared with those who did not [UFT (-)
      group, n = 36; P < 0.0001]. No amplification of the TS gene was observed in the
      carcinoma tissues in either group. The level of TS mRNA in the carcinoma tissues
      showed no significant difference between UFT (-) and UFT (+) groups. There was a
      significant correlation between the level of TS mRNA and TS in the UFT (-) group,
      as shown by simple linear regression analysis (P < 0.05). In the UFT (+) group, 9
      of 12 cases showed TSf corresponding to their level of TS mRNA. It seemed that
      the augmentation of TStot is the result of accumulation of ternary complex. Thus,
      TS inhibition by FdUMP will be insufficient in the absence of
      methylenetetrahydrofolate in the cytosol, because translation of TS from TS mRNA
      has been shown to continue in the presence of FdUMP.

PMID- 7641210
TI  - Estrogen promotes chemotherapeutic drug resistance by a mechanism involving Bcl-2
      proto-oncogene expression in human breast cancer cells.
AB  - Recent studies have shown that the Bcl-2 protein suppresses programmed cell death
      or apoptosis induced by a variety of stimuli including chemotherapeutic drugs.
      Because estrogen promotes the survival of estrogen-dependent breast cancer cells
      in vivo, we investigated whether estrogen might regulate levels of Bcl-2 gene
      expression in an estrogen-responsive human breast cancer cell line. Estrogen
      receptor-positive MCF-7 human breast cancer cells cultured in the presence of
      estrogen express the 8.5-kb Bcl-2 mRNA transcript. Depletion of estrogen from the
      medium results in loss of expression of the mRNA, whereas reexposure to estrogen
      markedly induces the Bcl-2 transcript. The changes in Bcl-2 mRNA are paralleled
      by changes in Bcl-2 protein levels. Estrogen-induced increases in Bcl-2 are
      significantly inhibited by inclusion of the pure antiestrogen ICI 164,384 in the
      medium. The Bax protein that heterodimerizes with Bcl-2 and promotes cell death
      is expressed in MCF-7 cells grown in the presence of estrogen and is unaffected
      by culture in estrogen-free medium. Estrogen depletion doubles the sensitivity of
      MCF-7 cells to the cytotoxic effects of Adriamycin compared with cells cultured
      in medium supplemented with estrogen, consistent with a decrease in the Bcl-2
      levels. MCF-7 cells treated simultaneously with estrogen and ICI 164,384 exhibit
      markedly lower resistance to Adriamycin compared with cells treated with estrogen
      alone. In the absence of estrogen, MCF-7 cells transfected with Bcl-2 expression
      plasmids display a marked increase in resistance to Adriamycin. In the presence
      of estrogen, MCF-7 cells expressing Bcl-2 antisense transcripts are rendered
      twice as sensitive to acute Adriamycin cytotoxicity as a control clone. We
      conclude that estrogen can promote resistance of estrogen receptor bearing human
      breast cancer cells to chemotherapeutic drugs through a mechanism that involves
      regulation of the Bcl-2 proto-oncogene.

PMID- 7641211
TI  - Inhibition of mammary gland involution is associated with transforming growth
      factor alpha but not c-myc-induced tumorigenesis in transgenic mice.
AB  - Deregulated expression of transforming growth factor alpha (TGF-alpha) or c-myc
      has been implicated in the genesis of human breast cancer. To better characterize
      the role of these molecules in this disease, we generated transgenic mice that
      express TGF-alpha or c-myc under control of the mouse whey acidic protein (WAP)
      promoter. We then compared the resulting mammary gland neoplasia in these mice
      and in previously described mice expressing a metallothionein-driven TGF-alpha
      transgene. Nonvirgin female mice in all transgenic lineages developed mammary
      tumors with 100% incidence but variable latency. Among TGF-alpha lines, mean
      survival time correlated with the level of transgene expression, and the average
      life spans of high-expressing WAP-TGF-alpha and WAP-c-myc mice were similarly
      reduced. The majority of TGF-alpha-induced tumors were relatively well
      differentiated adenomas and adenocarcinomas; in contrast, WAP-c-myc tumors were
      poorly differentiated, solid carcinomas with a minority of adenocarcinomas. Most
      TGF-alpha and all c-myc-induced tumors were transplantable, but lung metastases
      were infrequently observed in all transgenic lines. WAP-TGF-alpha-induced tumors,
      in marked contrast to those induced by WAP-c-myc, displayed frequent induction of
      cyclin D1 mRNA, suggesting that expression of this gene may complement that of
      TGF-alpha during mammary tumor development. Expression of TGF-alpha also induced
      precocious development of pregnant glands and delayed or inhibited mammary
      involution. As a result, multiparious MT-TGF-alpha and especially WAP-TGF-alpha
      females accumulated large numbers of hyperplastic alveolar nodules that resembled
      the more differentiated TGF-alpha-induced tumors. Finally, coexpression of WAP-c
      myc and WAP-TGF-alpha transgenes markedly decreased tumor latency, increased
      tumor growth, and even induced mammary tumors in virgin female and male mice.
      These findings provide further evidence for the importance of deregulated TGF
      alpha expression in multistage carcinogenesis, and they suggest that in the
      mammary gland the mechanism of TGF-alpha-induced transformation may depend on
      postlactational survival of differentiated epithelium. They also provide evidence
      of a potent tumorigenic collaboration between TGF-alpha and c-myc in mammary
      epithelium.

PMID- 7641212
TI  - Transforming growth factor beta 1 inhibits mouse keratinocytes late in G1
      independent of effects on gene transcription.
AB  - Potential mechanisms by which transforming growth factor beta 1 (TGF beta 1)
      inhibits cell growth include suppression of transcription of genes required for
      proliferation and inactivation of enzymatic activities that regulate progression
      through G1. To clarify which events are important for TGF beta 1 signaling, we
      have defined more precisely the times in G1 when the mouse keratinocyte cell line
      BALB/MK is sensitive to TGF beta 1-induced inhibition. TGF beta 1 is capable of
      inhibiting BALB/MK cell growth when the inhibitory factor is added to cells at
      any point before the G1-S transition. Synchronization at the G1-S boundary with
      mimosine, an inhibitor of initiation of origins of DNA replication, followed by
      release into S phase in the presence of TGF beta 1, indicated that cells lose
      sensitivity to TGF beta 1 as they enter the replicative phase. It is interesting
      that TGF beta 1 can inhibit BALB/MK cell growth late in G1, at a time when cell
      cycle progression is not blocked by an inhibitor of RNA polymerase II-mediated
      transcription. 5,6-dichlorobenzimidazole riboside (DRB). In addition, the ability
      of TGF beta 1 to inhibit entry into S phase in late G1 is unaffected by
      concurrent treatment with DRB. The data suggest that, at least when added to
      cultures that are in the latter few hours of G1, TGF beta 1 can inhibit cell
      cycle progression through mechanisms that do not involve stimulation or
      inhibition of gene expression at the transcriptional level.

PMID- 7641213
TI  - Re: M. D. Dabholkar et al., Malignant and nonmalignant brain tissues differ in
      their messenger RNA expression patterns for ERCC1 and ERCC2. Cancer Res., 55:
      1261-1266, 1995.

PMID- 7641215
TI  - Therapy of bovine ocular squamous-cell carcinoma with local doses of interleukin
      2: 67% complete regressions after 20 months of follow-up.
AB  - We have tested the therapeutic potency of peritumorally injected low doses of
      interleukin-2 (IL-2). Seventy tumours of the bovine ocular squamous-cell
      carcinoma (BOSCC), 1-3 cm in diameter, were treated with 5000, 20,000 or 200,000
      U IL-2 from Eurocetus (Chiron) to find the optimal dose for treatment. Injections
      were given peritumorally on Monday to Friday on 2 consecutive weeks. The size of
      the tumours was measured before treatment and 1, 3, 4, 9 and 20 months after
      treatment. After 9 months complete regression was observed in 89% of the tumours
      treated with 5000 U IL-2, 80% treated with 20,000 U and 67% treated with 200,000
      U. After 20 months, there was complete regression of 35%, 31% and 67% of the
      tumours respectively. The 9- and 20-month results of the 200,000-U treatment are
      significantly better than those of the 5000-U and 20,000-U treatments taken
      together. This protocol may be useful to treat advanced inoperable tumours (e.g.
      of the nasopharynx or skin) of human patients.

PMID- 7641214
TI  - High expression of adhesion molecules/activation markers with little interleukin
      2, interferon gamma, and tumor necrosis factor beta gene activation in fresh
      tumor-infiltrating lymphocytes from lung adenocarcinoma.
AB  - Little is known about the activation level of tumor-infiltrating lymphocytes
      (TIL) in human lung adenocarcinoma. We investigated the activation of fresh TIL
      at cellular and molecular levels and compared it with autologous and healthy
      normal peripheral blood lymphocytes (PBL) for baseline level. TIL were extracted
      from 12 primary lung adenocarcinomas by mechanical disruption without enzyme use
      and isolated by double-density Ficoll gradients. Flow-cytometry analysis of TIL
      subset distribution revealed that the majority was composed of T lymphocytes, and
      double labeling with alpha-CD3 and adhesion/activation markers revealed T cell
      subsets expressing CD49a, CD49b, CD54, and CD15, each of which was almost absent
      in autologous T peripheral blood lymphocytes (T-PBL). Moreover, the proportions
      of T-TIL expressing CD58, CD65, or CD25 were increased severalfold compared to T
      PBL. Lymphokine gene activation in TIL was assessed by mRNA reverse
      transcriptase/polymerase chain reaction (RT-PCR) and primers for interleukin(IL)
      2, IL-4, interferon (IFN) gamma, granulocyte/macrophage-colony-stimulating factor
      (GM-CSF), and tumor necrosis factor (TNF) beta. Semiquantitative comparisons
      between patients' TIL and PBL and healthy normal and activated PBL were performed
      by computerized image analysis. RT-PCR gel band products were quantified in
      relative units as a function of their size and intensity. TIL expressed
      detectable lymphokine mRNA but seemed poorly activated with respect to the total
      number of lymphokine genes and the amount of mRNA compared with alpha-CD3
      activated healthy PBL. IL-2, IFN gamma, and TNF beta did not appear to be
      expressed at higher levels in TIL than in autologous or healthy normal PBL.
      However, two-thirds of the patients had TIL distinguishable from autologous PBL
      by specific expression of GM-CSF and from healthy normal PBL by expression of IL
      4. These results show that lung adenocarcinoma TIL populations had little
      lymphokine gene activation despite the presence of several T cell subsets
      expressing different adhesion/activation markers. The lack or deficient
      combination of lymphokine production may be a factor that prevented efficient
      activation of TIL in these tumors.

PMID- 7641216
TI  - Functional properties of FC-2.15, a monoclonal antibody that mediates human
      complement cytotoxicity against breast cancer cells.
AB  - FC-2.15 is a murine IgM monoclonal antibody (mAb) that recognizes a cell-surface
      antigen (Ag2.15) expressed in most tumor-proliferating cells of human breast
      carcinomas and other neoplasias. In this study the cytotoxic ability of mAb FC
      2.15, its cell-surface binding properties and endocytosis in Ag2.15-expressing
      (Ag2.15+) cells were investigated. A 51Cr-release assay was used to test the FC
      2.15-mediated cytotoxicity. When human serum was used as source of complement, FC
      2.15 exerted a strong cytotoxic effect against human Ag2.15+ cells such as MCF-7
      (breast cancer cell line), primary breast carcinoma cells, polymorphonuclear
      leukocytes and chronic myeloid leukemia cells. The mAb concentration range was 1
      50 micrograms/ml. Cytotoxicity was completely abolished when complement was
      inactivated. Only 3.8 +/- 2.9% of MCF-7 cells survived the treatment with FC-2.15
      in the presence of human serum. A flow-cytometry assay was performed to study the
      Ag2.15 expression of the surviving cells and they were found to be Ag2.15-. FC
      2.15 did not mediate antibody-dependent cell cytotoxicity when different effector
      cells were used. Scatchard analysis with 125I-FC-2.15 on MCF-7 cells demonstrated
      an affinity constant of 6.9 x 10(7) M-1 and 2.8 x 10(6) antigenic sites/cell.
      125I-FC-2.15 was internalized to cytoplasmic vesicles reaching a maximum of 27%
      after 6 h incubation, followed by the release of labeled degradation products to
      the supernatant. FC-2.15 appears to exert its cytotoxic effect mainly in the
      presence of human complement, it reacts with intermediate affinity with a high
      density surface antigen, and it is slowly internalized by Ag2.15+ cells.

PMID- 7641217
TI  - Pharmacokinetics of anti-ganglioside GD2 mAb 14G2a in a phase I trial in
      pediatric cancer patients.
AB  - A phase I trial of a murine anti-ganglioside (GD2) monoclonal antibody (mAb)
      14G2a was conducted in 14 neuroblastoma patients and 1 osteosarcoma patient to
      assess its safety, toxicity and pharmacokinetics in pediatric patients. The
      pharmacokinetics of mAb 14G2a were biphasic with a t alpha 1/2 of 2.8 +/- 2.8 h
      and a t beta 1/2 of 18.3 +/- 11.8 h. In general, t beta 1/2 was dose-dependent
      with a level of significance of P = 0.036, and it reached a plateau at doses of
      250 mg/m2 or more. Overall the peak serum levels were dose-dependent at P <
      0.001. However, they demonstrated an abrupt increase between doses of 100 mg/m2
      and 250 mg/m2. The latter two suggest a saturable mechanism for mAb elimination.
      In addition, peak serum concentrations were observed earlier at higher mAb doses,
      which indicates the achievement of a steady state. The t beta 1/2 of mAb 14G2a in
      children appears to be shorter than in adults. Furthermore, 2 patients
      demonstrated a considerable decrease in t beta 1/2 following retreatment with
      14G2a. This was paralleled by high human anti-(mouse Ig) antibody levels. This
      study represents the first comprehensive analysis of murine mAb pharmacokinetics
      in children and will be useful in the future design of mAb therapy.

PMID- 7641218
TI  - Treating tumor-bearing mice with vitamin D3 diminishes tumor-induced myelopoiesis
      and associated immunosuppression, and reduces tumor metastasis and recurrence.
AB  - Metastatic Lewis lung carcinoma (LLC-LN7) tumors that secrete
      granulocyte/macrophage-colony-stimulating factor (GM-CSF) stimulate myelopoiesis
      and induce bone marrow-derived immunosuppressor cells that are homologous to
      granulocyte/macrophage progenitor cells. In vitro treatment of the LLC-LN7 cells
      with 1 alpha,25-dihydroxyvitamin D3 reduced tumor cell production of suppressor
      inducing activity, although suppressor-inducing activity could be restored by
      reconstituting the tumor supernatants with recombinant GM-CSF. Treatment of mice
      having LLC-LN7 tumors with vitamin D3 reduced tumor production of GM-CSF and the
      frequency of myeloid progenitor cells. This was associated with a reduction in
      immunosuppressor activity and an increase in T cell function. Vitamin D3
      treatment of mice having palpable tumors transiently retarded tumor growth, but
      caused a prominent reduction in tumor metastasis. Treating mice with vitamin D3
      after tumor excision resulted in a reduction in the tumor-induced myelopoietic
      stimulation and associated immunosuppressive activity, and enhanced T cell
      function. These mice had a markedly reduced incidence of tumor recurrence. The
      results of this study suggest that vitamin D3 treatment of mice with GM-CSF
      secreting tumors can interrupt the myelopoiesis-associated immunosuppressor
      cascade and, in turn, reduce tumor metastasis and recurrence.

PMID- 7641219
TI  - Antibody-independent phagocytosis of tumor cells by human monocyte-derived
      macrophages cultured in recombinant macrophage colony-stimulating factor.
AB  - Human monocytes exposed in vitro to recombinant macrophage-colony-stimulating
      factor (rhMCSF) differentiate into monocyte-derived macrophages (MDM), which
      mediate efficient antibody-dependent cytotoxicity (ADCC) against tumor cells. We
      and others have shown that this form of ADCC is unusual in that phagocytosis,
      rather than extracellular lysis, appears to play the major role in target cell
      killing. In this study, we asked whether the phagocytic form of cytotoxicity seen
      with ADCC could occur in the absence of an opsonizing antibody. We now report
      that, whereas cell lines derived from solid tumors are often resistant to
      antibody-independent cytotoxicity, malignant cells of lymphoid origin appear
      particularly susceptible to such antibody-independent killing. We found that all
      of nine lymphocytic leukemia and lymphoma cell lines tested in a total of 35
      experiments, plus all four samples of fresh leukemic blasts, were consistently
      susceptible to antibody-independent MDM cytotoxicity. Antibody-independent
      cytotoxicity against these cells was efficient (40%-63% killing) at effector:
      target (E:T) ratios as low as 2:1. Like ADCC, antibody-independent cytotoxicity
      involved phagocytosis of target cells, as demonstrated by ingestion of
      fluorescently labeled targets and analysis by flow cytometry. At the time of
      phagocytosis, the majority of target cells retained membrane integrity, as
      indicated by the direct transfer of intracellular [51Cr]chromate from
      radiolabeled targets to phagocytosing MDM, without release of the label into the
      medium. However, in contrast to ADCC, we found that the degree of antibody
      independent cytotoxicity was not a function of the E:T ratio. Instead, a constant
      proportion of the available target cells were killed regardless of the E:T ratio,
      suggesting that target cell recognition, rather than effector cell potency, might
      be the limiting factor in determining cytotoxicity. In additional experiments, we
      have also identified a second tumor cell type, nueroblastoma, as being
      susceptible to antibody-independent phagocytosis (all of five cell lines tested,
      cytotoxicity 40%-93%, E:T = 3:1). Our data thus indicate that the cytotoxicity
      induced by rhMCSF is not confined to antibody-mediated killing, and that
      phagocytosis can play a significant role in target cell destruction even in the
      absence of opsonizing antibody.

PMID- 7641221
TI  - Graft-versus-host disease following interleukin-2/lymphokine-activated killer
      (LAK) cell immunotherapy in a patient with acute myelogenous leukaemia in second
      complete remission: autologous LAK cells following allogeneic bone marrow
      transplantation are donor-derived.
AB  - A 48-year-old man was treated by allogeneic bone marrow transplantation (BMT) in
      first remission of M4 acute myelogenous leukaemia (AML). He experienced no graft
      versus-host disease (GVHD) and 7 months later he relapsed. Following further
      chemotherapy, he entered a second complete remission; however, he refused a
      further allogeneic or autologous BMT but agreed to immunotherapy with interleukin
      2 and autologous lymphokine-activated killer (LAK) cells. He tolerated this
      treatment well but went on to develop grade II skin GVHD. Polymerase chain
      reaction studies of DNA microsatellites of the autologous LAK cells showed that
      they were of donor origin. The patient remained well for 9 months until,
      immediately following the introduction of prednisolone for his persistent GVHD,
      he relapsed. He declined further active treatment and died 5 months later. The
      case shows that IL-2/LAK cells can be safely given to patients who have
      experienced no GVHD following allo-BMT and are likely to be effective through an
      ongoing graft-versus-leukaemia effect.

PMID- 7641220
TI  - Lymphocytes infiltrating colorectal cancer have low proliferative capacity but
      can secrete normal levels of interferon gamma.
AB  - Significant numbers of infiltrating mononuclear cells are commonly observed in
      solid tumours, although their role in restricting tumour growth is not clear.
      Tumour-infiltrating lymphocytes (TIL) from 38 patients with colorectal cancer, in
      parallel with peripheral blood lymphocytes (PBL), were assayed to determine their
      ability to proliferate in response to concanavalin A (ConA), interleukin-2 (IL
      2), ConA+IL-2, phorbol 12-myristate 13-acetate (PMA)+ionomycin ionomycin (IOM),
      and staphylococcal enterotoxin B(SEB). These reagents were selected to give a
      range of weak to strong proliferative responses either via or independent of the
      T cell receptor. Proliferation of TIL was significantly lower than that of PBL in
      all cultures: ConA (P < 0.001), IL-2 (P = 0.002), ConA+IL-2 (P < 0.001), PMA+IOM
      (P < 0.001), SEB (P = 0.002). In addition to the low proliferative capacity of
      TIL, production of cytokines by TIL may also play a role in control of tumour
      growth. We have assayed IFN gamma production in the supernatants from 16 paired
      TIL and PBL cultures, and tumour necrosis factor alpha (TNF alpha) in 6 paired
      cultures. TNF alpha concentrations were significantly lower in TIL cultures than
      in PBL cultures stimulated with ConA (P < 0.05), but no different in control or
      IL-2 stimulated cultures. IFN gamma levels did not significantly differ between
      PBL and TIL cultures, indicating that despite the restricted proliferative
      capacity of TIL, these cells remain capable of secreting significant amounts of
      IFN gamma.

PMID- 7641223
TI  - Metal-Induced Alterations in Excitable Membranes. Proceedings of a conference.
      Tihany, Hungary, July 22-24, 1993.

PMID- 7641222
TI  - The public health significance of metal neurotoxicity.

PMID- 7641224
TI  - GABA receptor-channel complex as a target site of mercury, copper, zinc, and
      lanthanides.
AB  - 1. The GABAA receptor-chloride channel complex has been shown to be modulated by
      a variety of chemicals. Scores of chemicals with diverse and unrelated structures
      augment the GABA-induced chloride current, while some other chemicals suppress
      the current. Certain heavy metals and a variety of polyvalent cations increase or
      decrease the current in a potent and efficacious manner. 2. We have studied the
      mechanisms whereby mercury, copper, zinc, and lanthanides modulated the GABA
      system by whole-cell and single-channel patch clamp techniques as applied to the
      rat dorsal root ganglion neurons in primary culture. 3. Mercuric chloride
      augmented the GABA-induced current to 115% of control at 0.1 microM and to 270%
      of control at 100 microM. It also generated a slowly developing inward current
      carried by a variety of ions. In contrast, methylmercury suppressed the GABA
      induced current. The potent stimulation of the GABA system by mercuric chloride
      is deemed important in mercury intoxication. 4. Copper and zinc suppressed the
      GABA-induced current with an EC50 of 16 and 19 microM, respectively. They bound
      to a common site on the external surface of the GABA receptor-channel complex. 5.
      Lanthanum augmented the GABA-induced current with an EC50 of 230 microM by
      increasing the affinity of the receptor for GABA. It bound to a site on or near
      the external surface of the GABA receptor-channel complex which is different from
      the sites for GABA, barbiturates, benzodiazepines, picrotoxin, and copper/zinc.
      6. Six other lanthanides with larger atomic numbers also exerted the same
      stimulatory effect with their efficacies increasing with the atomic number. 7.
      Single-channel analyses have revealed that the augmentation of whole-cell current
      by terbium, a lanthanide, is due to three actions: an increase in the overall
      mean open time, a decrease in the overall mean closed time, and an increase in
      the overall mean burst time.

PMID- 7641225
TI  - Astrocytes as potential modulators of mercuric chloride neurotoxicity.
AB  - 1. MC has been shown to inhibit the uptake of L-glutamate and increase D
      aspartate release from preloaded astrocytes in a dose-dependent fashion. 2. Two
      sulfhydryl (SH-)-protecting agents; reduced glutathione (GSH), a cell membrane
      nonpenetrating compound, and the membrane permeable dithiothreitol (DTT), have
      been shown consistently to reverse the above effects. MC-induced D-aspartate
      release is completely inhibited by the addition of 1 mM DTT or GSH during the
      actual 5-min perfusion period with MC (5 microM); when added after MC treatment,
      DTT fully inhibits the MC-induced D-aspartate release, while GSH does not. 3.
      Neither DTT nor GSH, in the absence of MC, have any effect on the rate of
      astrocytic D-aspartate release. Other studies demonstrate that although MC
      treatment (5 microM) does not induce astrocytic swelling, its addition to
      astrocytes swollen by exposure to hypotonic medium leads to their failure to
      volume regulate. 4. Omission of calcium from the medium greatly potentiates the
      effect of MC on astrocytic D-aspartate release, an effect which can be reversed
      by cotreatment of astrocytes with the dihydropyridine Ca(2+)-channel antagonist
      nimodipine (10 microM), indicating that one possible route of MC entry into the
      cells is through voltage-gated L-type channels.

PMID- 7641226
TI  - Effect of HgCl2 on acetylcholine, carbachol, and glutamate currents of Aplysia
      neurons.
AB  - 1. Using conventional two-microelectrode voltage-clamp techniques we studied the
      effects of inorganic mercury (HgCl2) on acetylcholine-, carbachol-, and glutamate
      activated currents on Aplysia neurons. Hg2+ was applied with microperfusion. 2.
      Acetylcholine and carbachol activated an inward, sodium-dependent current in the
      anterior neurons of the pleural ganglion. The medial neurons gave a biphasic
      current to acetylcholine and carbachol, which was outward at resting membrane
      potential. The faster component was Cl- dependent and reversed at about -60 mV,
      while the slower component was K+ dependent and reversed at greater than -80 mV.
      3. Hg2+ (0.1-10 microM) caused a dramatic increase in the acetylcholine- and
      carbachol-induced inward current in anterior neurons and the fast Cl- current in
      medial neurons. With only a 1-min preapplication of Hg2+, the acetylcholine- or
      carbachol-activated sodium or chloride currents were increased to 300% and the
      effect was only partly reversible. The threshold concentration was 0.1 microM
      Hg2+. 4. Contrary to the effects on sodium and chloride currents, concentrations
      of 0.1-10 microM Hg2+ caused a complete and irreversible blockade of K(+)
      dependent acetylcholine and carbachol currents. The block of the potassium
      current was relatively fast and increased with time. The concentration of HgCl2
      that gave a half-maximal blockade of the carbachol-activated potassium current
      was 0.89 microM. The chloride-dependent current elicited by glutamate on medial
      neurons was increased by HgCl2 as well. 5. These results suggest that actions at
      agonist-activated channels must be considered as contributing to mercury
      neurotoxicity. It is possible that the toxic actions of Hg2+ on synaptic
      transmission at both pre- and postsynaptic sites are important factors in the
      mechanism of Hg2+ toxicity.

PMID- 7641227
TI  - Mercuric(II) chloride modulates single-channel properties of carbachol-activated
      Cl- channels in cultured neurons of Aplysia californica.
AB  - 1. The effect of mercuric(II) chloride on kinetic parameters of carbachol
      activated single chloride channels were studied in cultured neurons of the marine
      mollusk, Aplysia californica. 2. Single neurons of Aplysia were cultured in L-15
      medium containing 1 mM beta-D-xyloside, which improved the success rate for
      gigaseal formation by 46%. Carbachol-activated single chloride channels were
      recorded in the cell-attached patch clamp configuration. Recordings with control
      solution (1 microM carbachol) and with test solution (1 microM carbachol + 1
      microM HgCl2) were performed successively on the same neuron. 3. In both the
      control and the test solution the open and closed time distributions were fitted
      with a double-exponential function. However, kinetic analysis revealed that Hg2+
      caused a significant reduction of the mean closed time (10.37 +/- 1.08 vs. 3.32
      +/- 0.02 msec) and of the second time constant tau 2 of the closed time
      distribution (2.09 +/- 0.05 vs. 0.66 +/- 0.5 msec). The reduction of tau 2, i.e.,
      fewer events in the longer closed state under the action of Hg2+, may be the
      physical cause for the reduction of the mean closed time and thus underlies the
      increased open probability p0 (0.13 +/- 0.01 vs. 0.29 +/- 0.01 msec) of carbachol
      activated chloride channels. 4. Inorganic Hg2+ affects the acetylcholine receptor
      at lower concentrations than previously reported.

PMID- 7641229
TI  - Zinc modulates A-type potassium currents and neuronal excitability in snail
      neurons.
AB  - 1. Zinc-induced actions were studied on the A-current and neuronal activity in
      identified and unidentified nerve cells of the snail, Helix pomatia, L., under
      voltage and current clamp conditions. 2. Extracellularly applied Zn2+ attenuated
      the peak amplitude of the A-current in a potential- and dose-dependent way (Ki =
      1.8 mM at -30 mV, nH = 0.6). 3. Attenuation of the A-currents was initiated as
      Zn2+ shifted the potential dependence of both activation and inactivation of the
      currents toward more positive potential values. 4. Zinc concomitantly prolonged
      the time to peak and the decay time constant of the A-currents (Kd = 1.7 mM, nH =
      1.4) as well. 5. Zn2+ decreased the resting membrane potential and the spike
      amplitude and increased the action potential duration and the input resistance of
      the cells in current clamp experiments. 6. A complex action of zinc increased the
      neuronal excitability, indicating spontaneous and synaptically evoked spike
      discharges. 7. Common and specific zinc binding sites are supposed on vertebrate
      and invertebrate A-type potassium channel proteins, where binding Zn2+ can
      modulate the gating properties and kinetics of the fast outward potassium
      currents.

PMID- 7641228
TI  - Mercury (Hg2+) and zinc (Zn2+): two divalent cations with different actions on
      voltage-activated calcium channel currents.
AB  - 1. We examined the actions of mercury (Hg2+) and zinc (Zn2+) on voltage-activated
      calcium channel currents of cultured rat dorsal root ganglion (DRG) neurons,
      using the whole-cell patch clamp technique. 2. Micromolar concentrations of both
      cations reduced voltage-activated calcium channel currents. Calcium channel
      currents elicited by voltage jumps from a holding potential of -80 to 0 mV
      (mainly L- and N-currents) were reduced by Hg2+ and Zn2+. The threshold
      concentration for Hg2+ effects was 0.1 microM and that for Zn2+ was 10 microM.
      Voltage-activated calcium channel currents were abolished (> 80%) with 5 microM
      Hg2+ or 200 microM Zn2+. The peak calcium current was reduced to 50% (IC50) by
      1.1 microM Hg2+ or 69 microM Zn2+. While Zn2+ was much more effective in reducing
      the T-type calcium channel current--activated by jumping from -80 to -35 mV--Hg2+
      showed some increased effectiveness in reducing this current. 3. The effects of
      both cations occurred rapidly and a steady state was reached within 1-3 min.
      While the action of Zn2+ was not dependent on an open channel state, Hg2+ effects
      depended partially on channel activation. 4. While both metal cations reduced the
      calcium channel currents over the whole voltage range, some charge screening
      effects were detected with Hg2+ and with higher concentrations (> 100 microM) of
      Zn2+. 5. As Zn2+ in the concentration range used had no influence on resting
      membrane currents, Hg2+ caused a clear inward current at concentrations > or 2
      microM.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7641230
TI  - Lead as an inductor of some morphological and functional changes in synaptosomes
      from rat brain.
AB  - 1. The effect of lead (in vivo) on the uptake of GABA, dopamine, and histidine as
      a precursor of histamine in synaptosomes obtained from chronically lead-treated
      rats was studied. 2. Lead decreased the uptake of GABA, increased the uptake of
      dopamine, and did not change the uptake of histidine. These effects were
      independent of calcium concentration. 3. Lead administration to the rat changed
      the morphology of the synaptosomes, as manifested in the decreased number of
      synaptic vesicles and disturbed mitochondrial structure. 4. The results suggest
      the existence of several mechanisms of lead toxicity on uptake, related to
      individual neurotransmitters, which are not necessarily connected with a
      Pb2+/Ca2+ interaction.

PMID- 7641231
TI  - Pb2+ reduces voltage- and N-methyl-D-aspartate (NMDA)-activated calcium channel
      currents.
AB  - 1. While intracellular calcium concentrations are closely regulated, two types of
      ion channels in neurons allow calcium influx: both voltage-activated and NMDA
      activated channels are significantly permeable to calcium. In this study we
      compare the effects of lead (Pb2+) on currents carried through voltage-activated
      calcium channels and NMDA-activated channels. 2. Pb2+ reduces voltage-activated
      calcium channel currents elicited by a voltage jump from -80 to 0 mV at 0.1 to 1
      microM, with an IC50 of 0.64 microM and a Hill slope of 1.22. This effect was
      partially reversible and not voltage dependent. Sodium and potassium currents
      were relatively unaffected at Pb2+ concentrations sufficient to block calcium
      channel currents by more than 80%. Pb2+ is, thus, a potent, reversible and
      selective blocker of voltage-dependent calcium channel currents. 3. A fast
      reversible and slow irreversible blocking action of Pb2+ was found on NMDA
      activated currents. When Pb2+ was applied simultaneously with aspartate and
      glycine (Asp/Gly), the inward currents were rapidly and reversibly reduced in a
      dose-dependent manner with a minimum effective concentration below 2 microM and a
      total blockade (> 80%) with 100 microM Pb2+. The IC50 was approximately 45 microM
      and the Hill coefficient 1.1. Preincubation with 50 microM Pb2+ resulted in a
      greater reduction in the response to Asp/Gly/Pb2+. This effect was reversed
      within 2 to 5 sec of wash. The lack of voltage dependence suggests that Pb2+ does
      not block the channel but rather alters the binding of agonists. Prolonged
      superfusion of a cell with the Asp/Gly/Pb(2+)-containing external solution
      resulted in a slow and irreversible decrease in the Asp/Gly activated
      current.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7641232
TI  - Long-term potentiation in the piriform cortex is blocked by lead.
AB  - 1. Long-term potentiation (LTP) is a prolonged increase in synaptic efficacy that
      is triggered by a brief tetanic stimulation at certain central synapses. LTP is
      one of the best available model systems available to the neurophysiologist of
      neuronal plasticity such as that underlying learning and memory. 2. We have
      studied the susceptibility of LTP to blockade by lead as a test of the hypothesis
      that the negative effect of lead on intelligence in children may result from
      interference with this process. LTP was studied in slices of rat piriform cortex.
      At this site, as in many other central synapses, LTP requires activation of
      postsynaptic N-methyl-D-aspartate (NMDA) receptors, and we investigated whether
      lead actions, if any, were mediated via effects on NMDA-activation ion channels
      or, alternatively, at voltage-activated calcium channels. 3. We find that lead
      blocks LTP at low micromolar concentrations. However, concentrations of lead that
      totally block LTP had no apparent effect on either NMDA-activated responses or
      presynaptic calcium channels, as monitored by transmitter release from
      presynaptic terminals. 4. While the mechanism of lead blockade of LTP remains to
      be determined, these observations are consistent with the hypothesis that the
      cognitive effects of lead neurotoxicity may result from effects on LTP.

PMID- 7641233
TI  - Modulation of synaptic events by heavy metals in the central nervous system of
      mollusks.
AB  - 1. The effects of heavy metals (Pb2+, Hg2+, and Zn2+) on synaptic transmission in
      the identified neural network of Helix pomatia L. and Lymnaea stagnalis L.
      (Gastropoda, Mollusca) were studied, with investigation of effects on inputs and
      outputs as well as on interneuronal connections. 2. The sensory input running
      from the cardiorenal system to the central nervous system and the synaptic
      connections between central neurons were affected by heavy metals. 3. Lead and
      mercury (10(-5)-10(-3) M) eliminated first the inhibitory, then the excitatory
      inputs running from the heart to central neurons. At the onset of action lead
      increased the amplitude of the excitatory postsynaptic potentials, but blockade
      of sensory information transfer occurred after 10-20 min of treatment. 4. The
      monosynaptic connections between identified interneurons were inhibited by lead
      and mercury but not by zinc. Motoneurons were found to be less sensitive to heavy
      metal treatment than interneurons or sensory pathways. 5. The treatment with Pb2+
      and Hg2+ often elicited pacemaker and bursting-type firing in central neurons,
      accompanied by disconnection of synaptic pathways, manifested by insensitivity to
      sensory synaptic influences. 6. Zn2+ treatment also sometimes induced pacemaker
      activity and burst firing but did not cause disconnection of the synaptic
      transmission between interneurons. 7. A network analysis of heavy metal effects
      can be a useful tool in understanding the connection between their cellular and
      their behavioral modulatory influences.

PMID- 7641234
TI  - Action of lead on glutamate-activated chloride currents in Helix pomatia L.
      neurons.
AB  - 1. In molluscan neurons glutamate may, on different neurons, evoke either
      excitation or inhibition. We studied neurons of Helix pomatia which have
      hyperpolarizing responses to glutamate and determined the effects of lead on
      these responses. 2. In voltage clamp experiments, the reversal potentials of
      these glutamate responses indicate that they are due to a conductance increase to
      chloride ions. Further evidence for this conclusion was obtained by the
      demonstration that responses to glutamate remained unaffected in experiments with
      intracellular dialysis with K-free saline in the presence of Na- and K-free
      extracellular media. In these circumstances, there is effectively no other ion
      than chloride to carry the current. In isolated neurons the glutamate-evoked
      chloride current is concentration dependent between 25 and 2500 microM. The
      current rises over 200 msec and declines in the continued presence of glutamate
      over a period of about 3 sec. 3. Lead (0.5-1.0 microM) potentiated the glutamate
      evoked chloride current provided that the channels were not maximally activated.
      The potentiation was greater if lead was added 30-60 sec before glutamate
      application. 4. These results suggest that potentiation of transmitter-evoked
      responses by lead must be considered as yet another possible site of action of
      lead on neurons, and thus this effect must be considered as a part of the
      mechanism responsible for the neurotoxicity of this heavy metal.

PMID- 7641235
TI  - Effects of chronic exposure to cadmium- or lead-enriched environments on ionic
      currents of identified neurons in Lymnaea stagnalis L.
AB  - 1. Voltage-activated ionic currents of three identified neurons of Lymnaea
      stagnalis L. were compared in control snails and in animals having been exposed
      to a cadmium- or lead-enriched environment for 2 weeks. We determined the
      presence, amplitude, and changes, if any, in the current-voltage characteristics
      of calcium and potassium currents in each of the three neurons from each of the
      three groups of animals. Finally, we have compared the effects of acute
      administration of Cd2+ or Pb2+ on neurons from control and chronically exposed
      animals. 2. Chronic exposure to cadmium resulted in a near doubling of the high
      voltage-activated calcium current. 3. No differences were found in the effects of
      acute application of Cd2+ or Pb2+ on neurons of pretreated and control animals.
      Cadmium was a potent blocker of the Ca current in either case, while lead caused
      only a 20% inhibition of the Ca current in neurons of both control and lead
      exposed animals. 4. Potassium currents were affected in both Cd(2+)- and Pb(2+)
      exposed animals. While the sustained outward current was not influenced
      noticeably, the fast K current was affected in different ways in different
      neurons. Some did not show this current in the controls but expressed it in
      neurons from the exposed animals. Other neurons showed the current in the
      controls and its depression in exposed animals. Acute application of cadmium did
      not modulate the K current, but lead enhanced the peak amplitude of the transient
      K current in neurons of both exposed and control snails.

PMID- 7641236
TI  - Metal ion-induced permeability changes in cell membranes: a minireview.
AB  - 1. The paper summarizes the effects of the metal ions Cu2+, Pb2+, Ag+, Hg2+,
      Zn2+, and Cd2+ applied externally or internally to the surface membrane of
      different excitable cells. 2. Conductance changes induced by metal ions, and
      metal ion-activated current, are compared with respect to their ion and voltage
      dependence. 3. It is suggested that metal ion-induced effects can be realized
      through special structures of the cell membrane, the metal ion "receptors,"
      although other mechanisms, as, for example, competition for Ca-binding sites in
      the channel forming proteins, cannot be excluded.

PMID- 7641237
TI  - Studies of aluminum neurobehavioral toxicity in the intact mammal.
AB  - 1. Aluminum (Al) has been implicated in neurotoxic syndromes in several
      conditions, including Alzheimer's disease (AD). The developmental stage of the
      mammalian brain most susceptible to Al was determined in rabbits systematically
      exposed to Al during the prenatal, postnatal, or second month or for 1 month as
      adults or as aged subjects. Eyeblink reflex classical conditioning showed an Al
      induced learning deficit only in the adult and aged rabbits. 2. 4-Aminopyridine,
      which was reported to improve learning in AD subjects, attenuated the Al-induced
      learning deficit. 3. Conditioned eyeblink acquisition is slower in AD subjects
      than controls, supporting the Al-loaded rabbit as a model of some AD effects. 4.
      To determine if the Al-loaded rabbit modeled the AD cholinergic deficit,
      acetylcholine (Ach) overflow was measured in rabbit hippocampus using
      microdialysis. Aluminum pretreatment reduced basal and potassium-stimulated Ach
      overflow compared to controls. 5. Acetylcholine overflow increased as control
      rabbits acquired the conditioned eyeblink reflex, then subsequently decreased,
      although conditioned eyeblink performance continued. In contrast, Al-loaded
      rabbits showed a delay in conditioned eyeblink acquisition and greatly attenuated
      Ach overflow. The Al-induced attenuation of Ach overflow may contribute to the Al
      induced learning deficit. 6. Brain Al entry was studied using microdialysis of
      blood, brain, and lateral ventricle. Aluminum rapidly entered the brain and
      lateral ventricle. Frontal cortical Al was greater than lateral ventricular Al,
      suggesting that Al primarily enters the brain through the cerebral
      microvasculature. 7. The brain/blood Al ratio was always significantly less than
      1. This ratio was influenced by the Al form administered, brain site and animal
      species. Thus, there appears to be an active process moving Al out of brain
      extracellular fluid (ECF). 8. Brain and blood dialysate Ach concentrations were
      not different after cyanide addition to the dialysate, supporting the conclusion
      that an active process moves Al out of brain ECF.

PMID- 7641238
TI  - The effects of Al on the calcium currents in Helix neurons.
AB  - 1. The effects of aluminium (Al) on calcium (Ca) currents were investigated by
      using the conventional two-electrode voltage clamp technique in Helix pomatia
      neurons. The peak amplitude, kinetics, and voltage dependence of activation and
      inactivation of the Ca currents were studied in the presence of 10(-5)-10(-3) M
      AlCl3, at pH 6. 2. Al prolonged the rising phase of the Ca currents and therefore
      increased the time to peak at each command voltage step used. 3. There was no
      significant influence of Al on the peak amplitude of the Ca currents, but the
      voltage dependence of the time to peak, activation, and inactivation of the Ca
      currents shifted to more positive potentials as a consequence of Al treatment. 4.
      The leak currents were not influenced by Al up to 1 mM, which was the maximal
      dose applied. 5. The results support the suggestion that Al may modify the Ca
      homeostasis and that it exerts a neurotoxic effect, at least in part, by
      modulation of the Ca current of the neuronal membrane.

PMID- 7641239
TI  - Actions of aluminum on voltage-activated calcium channel currents.
AB  - 1. Extracellular and intracellular effects of aluminum (Al) on voltage-activated
      calcium channel currents (VACCCs) of cultured rat dorsal root ganglion (DRG)
      neurons were investigated. Al (0.54 to 5.4 micrograms/ml = 20-200 microM) applied
      extracellularly reduces VACCCs in a concentration-dependent manner. The IC50 was
      calculated to be 2.3 micrograms/ml (83 microM). All types of VACCCs were
      similarly reduced by Al treatment. A slight shift of the current-voltage relation
      to depolarized potentials was observed for higher Al concentrations (> 2
      micrograms/ml). The action of Al was found to be use dependent, with little
      recovery (max. 20%) after wash. 2. The effect of Al was highly pH dependent in
      the investigated range (pH 6.4 to 7.8). We observed a rightward shift of the
      concentration-response curve at pH 7.7 (IC50:3.1 micrograms/ml) and a leftward
      shift at pH 6.4 (IC50:0.56 microgram/ml) compared to the concentration-response
      curve at pH 7.3. 3. The VACCC declined when 2.7 micrograms/ml Al was added to the
      internal solution. A steady state was reached within a few minutes. Additional
      extracellular application of the same concentration lead to an additional
      decrease of the current. These observations strongly suggest the existence of
      both intracellular and extracellular accessible binding sites for Al on voltage
      activated calcium channels (VACCs). 4. The special characteristics of the action
      of Al on VACCCs, i.e., the irreversibility, use dependence, and pH dependence, as
      well as the additional internal binding site may contribute to its neurotoxicity.

PMID- 7641240
TI  - Combined actions of Pb2+, Zn2+, and Al3+ on voltage-activated calcium channel
      currents.
AB  - 1. Whole-cell patch clamp experiments were performed on rat dorsal root ganglion
      (DRG) neurons to investigate the actions of various combinations of Pb2+, Zn2+,
      and Al3+ on voltage-activated calcium channel currents (VACCCs). 2. Each of these
      metals has been shown to reduce VACCCs. 3. We investigated the effects of
      simultaneous application of two cations in the range of their IC50 values. For
      all possible combinations (Pb2+/Zn2+, Zn2+/Al3+, Al3+/Pb2+), independent of the
      order of application, we found additive actions on VACCCs. 4. We observed a 75%
      (+/- 9%) block of the control current when two cations were applied
      simultaneously. This observation is consistent with both, an action of two metals
      at the same site as well as independent actions at different locations of the ion
      channel. 5. The additivity of the effects should be taken into account for
      questions of public health and the assessment of threshold limits in cases of
      environmental contamination.

PMID- 7641242
TI  - Dietary migraine: recent progress in the red (and white) wine story.
AB  - The concept of dietary migraine as a clinical entity remains controversial. We
      review here such objective evidence that has been put forward for its existence.
      Red wine, in particular, is commonly alleged to initiate attacks in susceptible
      individuals. We discuss how some of its recently described pharmacological
      properties might trigger off the sequence of events leading to migrainous
      headache.

PMID- 7641241
TI  - Differential effects of heavy metal ions on Ca(2+)-dependent K+ channels.
AB  - 1. The ability of various divalent metal ions to substitute for Ca2+ in
      activating distinct types of Ca(2+)-dependent K+ [K+(Ca2+)] channels has been
      investigated in excised, inside-out membrane patches of human erthrocytes and of
      clonal N1E-115 mouse neuroblastoma cells using the patch clamp technique. The
      effects of the various metal ions have been compared and related to the effects
      of Ca2+. 2. At concentrations between 1 and 100 microM Pb2+, Cd2+ and Co2+
      activate intermediate conductance K+(Ca2+) channels in erythrocytes and large
      conductance K+(Ca2+) channels in neuroblastoma cells. Pb2+ and Co2+, but not
      Cd2+, activate small conductance K+(Ca2+) channels in neuroblastoma cells. Mg2+
      and Fe2+ do not activate any of the K+(Ca2+) channels. 3. Rank orders of the
      potencies for K+(Ca2+) activation are Pb2+, Cd2+ > Ca2+, Co2+ >> Mg2+, Fe2+ for
      the intermediate erythrocyte K+(Ca2+) channel, and Pb2+, Cd2+ > Ca2+ > Co2+ >>
      Mg2+, Fe2+ for the small, and Pb2+ > Ca2+ > Co2+ >> Cd2+, Mg2+, Fe2+ for the
      large K+(Ca2+) channel in neuroblastoma cells. 4. At high concentrations Pb2+,
      Cd2+, and Co2+ block K+(Ca2+) channels in erythrocytes by reducing the opening
      frequency of the channels and by reducing the single channel amplitude. The
      potency orders of the two blocking effects are Pb2+ > Cd2+, Co2+ >> Ca2+, and
      Cd2+ > Pb2+, Co2+ >> Ca2+, respectively, and are distinct from the potency orders
      for activation. 5. It is concluded that the different subtypes of K+(Ca2+)
      channels contain distinct regulatory sites involved in metal ion binding and
      channel opening. The K+(Ca2+) channel in erythrocytes appears to contain
      additional metal ion interaction sites involved in channel block.

PMID- 7641243
TI  - 5HT2 receptors in cerebral cortex of migraineurs studied using PET and 18F
      fluorosetoperone.
AB  - Since the brain 5HT2 receptors might be implicated in migraine pathogenesis, we
      have used positron emission tomography and 18F-fluorosetoperone, a 5HT2 specific
      radioligand, to investigate in vivo the cortical 5HT2 receptors in migraine
      subjects. Nine migraineurs who had either migraine with and without aura (n = 5)
      or only migraine without aura (n = 4) were studied between attacks. Twelve
      unmedicated healthy subjects of similar mean age were used as controls. Brain
      radioactivity was measured after 18F-setoperone IV injection for 90 min. A
      decrease of the regional specific distribution volumes (SDV) of the ligand was
      observed both in migraineurs and in controls. The age adjusted group means of SDV
      did not differ between patients and controls for the whole and for the right or
      left frontal, temporal, parietal and occipital cortex. These results suggest that
      cortical 5HT2 receptors may be unaltered between attacks in migraine sufferers.

PMID- 7641244
TI  - Cerebral blood flow velocities are reduced during attacks of unilateral migraine
      without aura.
AB  - It has been disputed whether or not large intracranial arteries are dilated
      during migraine attacks. In order to answer this question the present
      transcranial Doppler study focused on side-to-side differences of middle cerebral
      artery blood velocity during unilateral attacks of migraine without aura in 25
      patients. Blood velocity in the middle cerebral artery was lower on the headache
      side (59 cm/s) than on the non-headache side (65 cm/s) during the migraine
      attack. No such difference was found outside of attack (65 cm/s both sides). The
      difference (headache side minus non-headache side) was on average -6.1 cm/s
      during attack compared to -0.4 cm/s outside of attack (p = 0.01). Assuming that
      rCBF is unchanged during attacks of migraine without aura, our results suggest a
      9% increase in middle cerebral artery lumen (cross-sectional area) on the
      affected side during unilateral attacks of migraine without aura. The findings,
      however, do not necessarily mean that arterial dilatation is the only or even the
      most significant cause of pain.

PMID- 7641245
TI  - Thresholds for detection of a target against a background grating suggest visual
      dysfunction in migraine with aura but not migraine without aura.
AB  - Square-wave gratings with particular spatial characteristics induce visual
      illusions. Patients with migraine are particularly susceptible to these illusions
      and report discomfort. Their discomfort tends to be greater when the gratings are
      illuminated by red light, a tendency not shown by controls. Gratings that induce
      illusions have been found to impair the recognition of optically superimposed
      targets in headache-free control subjects. We measured the impairment of target
      detection under illuminants of various chromaticities in migraineurs with and
      without aura and in matched controls. Migraineurs with aura had significantly
      higher thresholds for target detection than either migraineurs without aura or
      controls; in addition, the effect of chromaticity was slightly more pronounced in
      both migraine groups than in the control group. These findings are consistent
      with a recent suggestion that migraine with aura might give rise to subclinical
      damage to the primary visual cortex.

PMID- 7641246
TI  - Contingent negative variation during migraine attack and interval: evidence for
      normalization of slow cortical potentials during the attack.
AB  - The contingent negative variation (CNV) amplitudes of 16 subjects with migraine
      without aura were studied during pain-free intervals and during attacks and the
      results were compared with those of 22 healthy subjects. In 32 trials the CNV
      amplitudes were calculated for (a) "total interval", (b) "early CNV component",
      (c) "late CNV component", and (d) habituation. There was a significantly higher
      total CNV amplitude in migraine subjects during pain-free intervals compared to
      that of the healthy subjects and migraine patients during an attack. Healthy
      subjects as well as subjects studied during the attack showed a significant
      habituation whereas migraine subjects studied during pain-free intervals did not.
      This suggests that the higher CNV amplitude in migraine patients studied between
      pain-free attacks may be due in part to impaired habituation.

PMID- 7641247
TI  - The effects of aspirin on the CNV in healthy individuals.
AB  - The effects of aspirin on the contingent negative variation (CNV) of 16 healthy,
      right-handed volunteers were studied in accordance with a placebo-controlled
      double-blind crossover design. Early and late CNV factors were measured. Aspirin
      caused a statistically significant decrease of the early wave and an increase of
      mean amplitude of the late wave. A central action of aspirin, affecting
      noradrenergic and dopaminergic structures, may be responsible for the CNV
      changes.

PMID- 7641248
TI  - Platelet and plasma levels of glutamate and glutamine in migraine with and
      without aura.
AB  - We evaluated plasma and platelet glutamate and glutamine levels in migraine with
      and without aura during headache-free periods and compared the results with those
      of normal controls. The plasma and platelet levels of glutamine in migraine with
      and without aura were normal. Migraine without aura patients had higher glutamate
      levels in plasma, and normal platelet levels. In migraine with aura patients,
      glutamate levels were high in platelets, but not in plasma. This suggests
      different profiles of excitatory amino acid metabolism in migraine with and
      without aura.

PMID- 7641249
TI  - Nocturnal melatonin excretion is decreased in patients with migraine without aura
      attacks associated with menses.
AB  - Nocturnal melatonin excretion was studied throughout a complete menstrual cycle
      in 10 women with migraine without aura attacks associated with menses and 9 women
      controls. Urine melatonin was determined by radioimmunoassay. The mean nocturnal
      melatonin excretion throughout the cycle was significantly lower in the migraine
      patients than in controls. In the control group, melatonin excretion increased
      significantly from the follicular to the luteal phase, whereas no difference was
      observed in the migraine group. Results are discussed in view of the role of the
      pineal gland in the organization of biological rhythms and homeostasis in
      relation to environmental conditions.

PMID- 7641250
TI  - Sex-hormone-related events in migrainous females. A clinical comparative study
      between migraine with aura and migraine without aura.
AB  - In this study, the relationship between hormonal-related events and migraine with
      aura (MA) and without aura (MO) was investigated. Subjects included 268 women
      suffering from MA (88) and MO (180). Data were collected on the relationship
      between sex-hormone-related events and migraine. Migraine during menses was
      observed in a significantly higher percentage of MO than MA patients (p < 0.03).
      Menstrual migraine was significantly more common in MO than in MA patients (p <
      0.01). Migraine began during pregnancy in a significantly higher percentage of MA
      than of MO patients (p < 0.01). No significant difference was observed between
      the two groups of patients regarding the onset of migraine at menarche, after
      menopause, in the postpartum period or during the early cycles of oral
      contraceptives. Also, both groups of patients showed a similar migraine course
      during pregnancy, oral contraceptive use and menopause. Eight patients with
      coexisting migraine with aura and migraine without aura attacks reported the
      appearance of the aura symptom for the first time in the early cycles of oral
      contraceptive intake. These findings suggest that gonadal hormone fluctuation may
      influence both types of migraine.

PMID- 7641251
TI  - Migraine, tension headache and left-handedness.
AB  - The Geschwind-Behan hypothesis, that migraine is more common among left-handed
      patients, was tested in 320 migraine sufferers. The frequency of left-handedness
      was also assessed in 68 tension headache patients and compared to that in 140
      healthy controls. No significant differences were observed. This study failed to
      support the association between migraine, tension headache and left-handedness
      using the IHS classification of headache.

PMID- 7641252
TI  - Non-invasive trigeminal evoked potentials: normative aging data.
AB  - A mild electric shock applied to the lower lip was used to elicit reliable evoked
      potentials from the trigeminal nerve in 50 normal adults who ranged in age from
      20 to 69 years. The waveforms were morphologically similar to those observed with
      invasive procedures. No substantial effects for subject age, side of stimulation,
      or recording electrode were obtained for any of the individual trigeminal evoked
      potential amplitudes or latencies. Female subjects tended to have somewhat larger
      amplitudes and shorter latencies than male subjects. The results suggest that non
      invasive procedures produce reliable evoked potential measures of trigeminal
      nerve function for patients of all ages.

PMID- 7641253
TI  - Increased adverse effects of opiates in migraine patients.

PMID- 7641254
TI  - Ictal TCD studies in migraine.

PMID- 7641255
TI  - Inhibition dysfunction in the primary visual cortex.

PMID- 7641256
TI  - Elongated styloid process and Eagle's syndrome.
AB  - A controversial entity, Eagle's syndrome, is reviewed. After an anatomical
      description of the maxillo-vertebro-pharyngeal region we summarize the causative,
      diagnostic and therapeutic aspects of the syndrome. Two different conditions are
      often reported as Eagle's syndrome: one characterized by dysphagia and unilateral
      pharyngeal pain radiating to the ear and worsened by swallowing; the other
      characterized by pain in the head and neck region due to compression of the
      neurovascular structure by an elongated styloid process. The latter also includes
      typical cranial neuralgias (such as glossopharyngeal neuralgia) and carotidynia.
      We believe that the term "Eagle's syndrome" is legitimate only in the first case
      and in those "atypical" painful head and neck conditions related to an elongated
      styloid process and relieved by styloidectomy. We believe Eagle's syndrome
      deserves consideration in the International Headache Classification.

PMID- 7641257
TI  - The nitric oxide hypothesis of migraine and other vascular headaches.
AB  - The molecular mechanisms of migraine pain remain to be determined. Our studies of
      glyceryl trinitrate (GTN)-induced and histamine-induced headaches have led us to
      propose that nitric oxide (NO) may be the causative molecule in migraine pain. We
      also propose that substances capable of inducing experimental vascular headache
      do so with NO as the common mediator. Finally, we suggest that drugs with
      antimigraine activity inhibit NO and the cascade of intracellular reactions
      triggered by NO. We believe these observations provide new insight into the
      mechanisms of vascular headache. The importance of NO as a potential initiator of
      the migraine attack indicates new directions for the pharmacological treatment of
      migraine and other vascular headaches.

PMID- 7641258
TI  - Recognizing and managing the difficult patient.
AB  - Expectations, history, attitudes, biases and experiences are part of the dentist
      patient relationship. How dentists manage these within themselves and within the
      delicate, complex dentist-patient relationship is the difference between a
      stressful day at the office and a satisfying dental experience for everyone
      involved.

PMID- 7641259
TI  - Making psychological referrals.
AB  - Although the actual occasions for doing so may be infrequent, it is important
      that the dentist be aware of how to make referrals for psychological reasons.

PMID- 7641260
TI  - Dentists mostly unified on health reform issues.

PMID- 7641262
TI  - Payment for a kid's first fillings and other thoughtful acts.

PMID- 7641261
TI  - Local study shows inner city schoolchildren do not receive appropriate dental
      care.

PMID- 7641263
TI  - Holistic dentistry: innovation or quackery?

PMID- 7641264
TI  - Molding our image: the media and dentistry.
AB  - Dentistry has had a few nasty media shocks in the past year. Part of the problem
      is that dentists who are willing to talk to the press in good times, shy away
      from the media when the questions get tough. And if you won't answer the
      question, what's a journalist--and the public--to think?

PMID- 7641265
TI  - Endodontic microsurgery.

PMID- 7641266
TI  - Infection control made simple.

PMID- 7641267
TI  - Five marketing myths and why they are wrong.
AB  - Marketing is a continual process of retaining current patients and attracting new
      patients. A practice markets itself daily by conveying an image that attracts and
      retains patients.

PMID- 7641268
TI  - Gloving up for the future.

PMID- 7641269
TI  - Endodontics: recapitulation and evolution.

PMID- 7641271
TI  - Taking prevention a major step forward.

PMID- 7641270
TI  - Why you should help your patients stop using tobacco.

PMID- 7641272
TI  - Helping snuff out tobacco use: preventive dentistry for the '90s.

PMID- 7641273
TI  - Abuse of children and older adults: uncanny parallels.
AB  - The violence around us seems to be growing. Daily we read or hear about children
      such as the 22-month-old girl who was found abandoned in a Chicago alley or a
      malnourished older adult living in squalor, while his or her adult child spends
      the parent's money. Can something be done?

PMID- 7641274
TI  - Dental sterilization practices--the Chicago story.

PMID- 7641275
TI  - Negotiating dental provider agreements.

PMID- 7641276
TI  - Brace yourself for retirement.

PMID- 7641278
TI  - No insurance--no treatment.

PMID- 7641277
TI  - Rescuing the victims of domestic violence: a disturbing selectivity.

PMID- 7641279
TI  - Our dental family.

PMID- 7641280
TI  - More dentists accept credit cards for payment of dental services.

PMID- 7641281
TI  - CDS survey shows 90% of local dentists offer pro bono care.

PMID- 7641282
TI  - Pre-implant planning: the key to repeated success.

PMID- 7641283
TI  - How to terminate a partnership or associateship without being sued.

PMID- 7641284
TI  - The majority report.

PMID- 7641285
TI  - Dental office safety.

PMID- 7641287
TI  - Esthetic root coverage in periodontics: a review.
AB  - Root coverage is a common, but challenging goal. The many options in surgical
      root coverage, their benefits and limitations are explored.

PMID- 7641286
TI  - They're not just gloves: a guideline on proper use.

PMID- 7641288
TI  - Freud's oral problems: the Chicago connection.

PMID- 7641289
TI  - Learning by the rules.

PMID- 7641290
TI  - The business of dentistry.

PMID- 7641291
TI  - Principles and applications of biosensors for bioprocess monitoring and control.
AB  - Biosensors are useful analytical devices that can be integrated with on-line
      process monitoring schemes. In this article, the principles and applications of
      these devices for bioprocess monitoring are considered. Several different types
      of biosensors are described, and the applications and limitations of flow
      injection analysis (FIA) for these applications are discussed. It is hoped that
      the background provided here can be useful to researchers in this area.

PMID- 7641292
TI  - Solvent selection for whole cell biotransformations in organic media.
AB  - Although they were used historically as antimicrobial agents, there is a modern
      requirement to devise organic solvent systems for exploitation in the
      biotransformation by intact cells of substrates that are poorly soluble in water.
      Water-immiscible solvents are normally less cytotoxic than are water-miscible
      ones. While a unitary mechanism is excluded, damage to the membrane remains the
      likeliest major mechanism of cytotoxicity, and may be conveniently assessed using
      an electronic biomass probe. Studies designed to account for the mechanisms of
      action of general anesthetics and of uncouplers parallel those designed to
      account for the cytotoxicity of organic solvents. Although there are hundreds of
      potential physical descriptors of solvent properties, many are broadly similar to
      each other, such that the intrinsic dimensionality of solvent space is relatively
      small (< 10). This opens up the possibility of providing a rational biophysical
      basis for the optimization of the solvents used for biotransformations. The
      widely used descriptor of solvent behavior, log P (the octanol:water partition
      coefficient), is a composite of more fundamental molecular descriptors; this
      explains why there are rarely good correlations between cytotoxicity and log P
      when a wide variety of solvents is studied. Although the intrinsic dimensionality
      of solvent space is relatively small, pure solvents still populate it rather
      sparsely. Thus, mixtures of solvents can and do provide the opportunity of
      obtaining a solvent optimal for a biotransformation of interest.

PMID- 7641293
TI  - Separate control of the survival, the self-renewal and the differentiation of
      hemopoietic stem cells.
AB  - Hemopoietic stem cells adhere to hemopoietic supportive (MS-5) cells, but not to
      non-supportive (MS-K) cells. Although a soluble stem cell factor (SCF) was
      produced by both of these cell lines, little activity was detectable in the
      supernatant from the cultures of either of these cells, indicating that SCF might
      be compartmentalized within the extracellular matrix (ECM), and transferred
      directly to the stem cells via the ECM (44). To probe this possibility, we
      studied the transfer of SCF from the ECM and the subsequent support of the
      survival of the hemopoietic stem cells. A stem cell-enriched bone marrow cell
      fraction was overlaid on SCF-containing ECM. The stem cells survived and
      proliferated for some days without differentiation under these conditions,
      whereas stem cells overlaid on ECM without SCF died within a few days. Addition
      of interleukin-3 (IL-3) to the ECM that contains SCF, induced differentiation of
      the stem cells. Granulocyte-macrophage colony-stimulating factor (GM-CSF) induced
      further differentiation of the stem cells, which was accompanied by a decrease in
      the number of colony-forming unit in spleen (CFU-S). These observations verified
      the above hypothesis, and indicated that the survival, the self-renewal, and the
      differentiation of hemopoietic stem cells can be separately controlled at least
      in vitro.

PMID- 7641294
TI  - Estrogen-depleted condition induces apoptosis of rat mammary cancer cells after
      entering the S-phase of the cell cycle.
AB  - To elucidate the relationship of estrogen-depleted condition to apoptosis and
      tumor regression, 7,12-dimethylbenz[a]anthracene-induced mammary cancers of
      Sprague-Dawley rats were ovariectomized or treated with the anti-estrogenic agent
      epitiostanol after which proliferative activity and the incidence of apoptosis
      were investigated using the nick end labeling method, agarose gel electrophoresis
      of DNA, electron microscopy, the BrdU-labeling method and mitotic count. Tumor
      regression was found after 7-day treatment, and apoptosis induced by the agent on
      the 3rd day was clearly shown in both agarose gel electrophoresis of DNA and
      electron microscopy, which are two major methods used to judge apoptosis. The
      incidence of apoptosis revealed by the nick end labeling method reached its
      maximum, about threefold the control level, on the 3rd day of epitiostanol
      treatment compared with control tumors (P < 0.01). The incidence of the cells
      incorporating BrdU reached its maximum of 9.7% on the 2nd day of the treatment,
      while the incidence in tumors without treatment was 7.5% (P < 0.05).
      Subsequently, the incidence of apoptosis was reduced after 7-day treatment, and
      the incidence of BrdU-positive cells was significantly reduced to about 3% after
      5-day treatment. The incidence of mitosis did not change until the 3rd day of the
      treatment and was reduced after 5-day treatment. Similarly, chronological changes
      of the incidences of BrdU-labeled cells, apoptotic cells and mitosis were
      observed in the tumors after ovariectomy. BrdU-labeled apoptotic bodies were
      detected in the tumors on the 3rd day in epitiostanol-treated rats that received
      a 6-hr bolus of BrdU before sacrifice.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7641295
TI  - CBP-140, a novel endoplasmic reticulum resident Ca(2+)-binding protein with a
      carboxy-terminal NDEL sequence showed partial homology with 70-kDa heat shock
      protein (hsp70).
AB  - Antibodies against pokeweed agglutinin binding proteins isolated from F9
      embryonal carcinoma cells were used to screen a lambda gt11 expression library
      constructed from the cells. A cDNA clone thus obtained encoded a novel calcium
      binding protein of 140 kDa (CBP-140). Antibodies raised against the CBP-140
      fusion protein stained a 140 kDa band in extracts not only from F9 cells but also
      from various mouse organs. A calcium blot experiment using CBP-140 fusion protein
      verified the calcium binding property of the protein. In the partial amino acid
      sequence so far clarified (652 amino acid residues) we could not detect EF-hand,
      but could detect contiguous acidic amino acids, which may serve as a calcium
      binding site. CBP-140 showed homology with 70-kDa heat shock protein, though it
      was not induced by heat shock treatment. Localization of CBP-140 in endoplasmic
      reticulum was shown by indirect immunofluorescence staining and also by
      subcellular fractionation. Amino acid sequence of CBP-140 contains a carboxyl
      terminal Asn-Asp-Glu-Leu (NDEL) sequence, which resembles Lys-Asp-Glu-Leu (KDEL)
      sequence, a signal to retain the resident proteins in endoplasmic reticulum; NDEL
      sequence may indeed play a similar role.

PMID- 7641296
TI  - Phosphoinositide signalling enzymes in human T lymphocytes: modulation of
      phosphoinositidase C isoform gamma 1 upon interferon treatment.
AB  - In human T lymphocytes immunoblotting analysis of phosphoinositidase C (PIC)
      isoforms has shown that gamma 1 is the most represented isoform both at the
      cytoplasmic and nuclear level, and that interferon beta produces, within 90 min
      of treatment, an increase of its expression. These results, also supported by
      immunoelectronmicroscopic investigation, strongly suggest the involvement of PIC
      gamma 1 in the cascade of molecular events generated by the interaction between
      interferon and its cell surface receptors.

PMID- 7641297
TI  - A novel method of preparing rat-monoclonal antibody-producing hybridomas by using
      rat medial iliac lymph node cells.
AB  - A novel method of preparing hybridomas producing rat monoclonal antibodies was
      established. The enlarged medial iliac lymph nodes from rats injected via hind
      footpads with an emulsion of antigen and Freund's adjuvant were used for cell
      fusion. Ovalbumin was used as a representative antigen. The incidence of
      hybridomas producing antibody of interest with this method was about 10 times
      higher than that of hybridomas with the conventional method using mouse or rat
      spleen cells. The average percentages of hybridomas producing IgG1, IgG2a, IgG2b
      and IgG2c were 37.1%, 47.0%, 15.9% and 0.0%, respectively. A single injection
      with antigen was sufficient for immunization in this method.

PMID- 7641298
TI  - Cotranslocation and colocalization of hsp40 (DnaJ) with hsp70 (DnaK) in mammalian
      cells.
AB  - A novel 40-kDa heat-shock protein hsp 40 in mammalian cells has been recently
      identified to be a homolog of bacterial DnaJ protein. We have previously shown
      the colocalization of hsc70 (p73, constitutive form) with hsp40 in the nucleoli
      of heat-shocked HeLa cells. In this report we further investigated intracellular
      translocation and localization of hsp40 and hsp70 (both constitutive p73 and
      inducible p72) in several mammalian cells. Translocation kinetics of hsp40 during
      heating at mild temperature were almost the same as those of hsp70 in HeLa cells.
      Hsp40 colocalized not only with hsc70 (p73) but also with hsp70 (p72) in heat
      shocked HeLa (human), HA-1 (Chinese hamster) and NRK (rat) cells. Direct
      interaction of hsp40 with hsp70 (p73 and/or p72) was observed in all cells tested
      by immunoprecipitation methods. Also, treatments of cells with cytoskeleton
      acting drugs such as cytochalasin E, colchicine and taxol had no effect on the
      heat-induced translocation of hsc70 (p73) and hsp40 in NRK cells. These results
      strongly suggest that hsp40 and hsp70 (p73/p72) form a complex in the cytoplasm
      at normal temperature, translocate together and colocalize in the nuclei and
      nucleoli upon heat-shock, and that they may function cooperatively to repair
      (refold) denatured proteins under stress conditions.

PMID- 7641300
TI  - A simplified general method for determination of recombinant retrovirus titers.
AB  - To construct recombinant retroviruses with only a single active promoter, we
      introduced point mutations into the TATA box region of the 3'-LTR, and
      successfully obtained high-titer virus with sufficient self-inactivating
      activity. However, the viral titer could not be determined by the number of G418
      resistant colonies since the neomycin resistance gene was under 5'-LTR control,
      because of inactivation of the selection marker in target glioma cells. To
      overcome this problem, we constructed PCR primers with homology to a gene under
      the control of the internal promoter of recombinant retrovirus, and to retrovirus
      specific sequences. There was good correlation between the amount of PCR
      amplified product and the number of colony forming units when glioma cells were
      transduced with the retroviruses containing both the neomycin resistance gene and
      the HTK gene. Amplified PCR products quantitated by densitometry after glioma
      cells were transduced with SIV retrovirus vectors, and there was good correlation
      between density and sensitivity to GCV following transduction. Therefore,
      detection of HTK PCR products from glioma cells transduced with HTK-bearing
      retroviruses is useful for determining the appropriate packaging cell for
      efficient production of viral particles. This detection system is especially
      useful for isolating high titer clones producing SIV-type retroviruses.

PMID- 7641301
TI  - Photodegradation kinetics of the new antibacterial fluoroquinolone derivative,
      orbifloxacin, in aqueous solution.
AB  - The photodegradation kinetics of orbifloxacin (1-cyclopropyl-5,6,8-trifluoro-1,4
      dihydro-7-(cis-3,5-dimethyl-1-pipe raz inyl)-4-oxoquinoline-3-carboxylic acid)
      was investigated in aqueous solution at various pH values (1.2-12.5) and at an
      ionic strength of 0.5. The photodegradation experiments were performed using a
      fluorescent or a chemical lamp as a light source and the cumulative number of
      photons during exposure was determined by a ferrioxalate actinometer. It was
      found that the photodegradation of orbifloxacin followed apparent first-order
      kinetics under both types of artificial light. The photodegradation rates of
      orbifloxacin in a neutral medium were higher than those in acidic and alkaline
      media. Orbifloxacin was most unstable in solution at pH 7.4, and its degradation
      half-life was 0.9 h. Also, the log k-pH profile indicated that the
      photodegradation rate of orbifloxacin was related to the dissociation of the
      carboxylic and dimethylpiperazinyl groups and the main photo-labile species was
      the zwitterionic form. In addition, the photodegradation kinetics of the
      decarboxylated derivative of orbifloxacin in aqueous solution was investigated to
      determine the effect of the functional groups on the photodegradation of
      orbifloxacin.

PMID- 7641299
TI  - TGF-beta completely blocks the formation of small-cell colonies: effects of mito
      inhibitory factors on the proliferation of primary cultured rat hepatocytes.
AB  - The proliferation of primary cultured rat hepatocytes was observed in serum-free
      modified DMEM supplemented with 10 mM nicotinamide and 10 ng/ml EGF. These
      proliferating cells were mainly mononucleate and formed small-cell colonies after
      4 days of culture. In the present experiment primary cultured hepatocytes were
      treated with Activin A, IL-1 beta, IL-6, and TGF-beta, which have been shown to
      be inhibitors of the DNA synthesis of rat hepatocytes, to examine whether these
      four inhibitors could suppress the formation of small-cell colonies. The initial
      DNA synthesis of more than 50% of the cells was dose-dependently inhibited by all
      the factors and the strongest inhibition was demonstrated in the cells treated
      with TGF-beta. Although Activin A and IL-6 did not block the colony development
      when the agents were administered at 96 h, just before the time when the cells
      started to form colonies, TGF-beta and IL-1 beta could inhibit the colony
      formation completely and partially, respectively. Transient treatment (48-72 h)
      with TGF-beta was enough to suppress colony development, while Activin A and IL-6
      did not block the formation of colonies. IL-1 beta partially suppressed this
      formation. However, continuous administration (48-144 h) of IL-beta as well as
      TGF-beta stimulated the detachment of the cells from dishes and the remaining
      hepatocytes failed to form colonies. In addition, only TGF-beta could inhibit the
      DNA synthesis of most small cells in the established colonies as well as that of
      relatively large hepatocytes. Neither Activin A, IL-1 beta nor IL-6 could inhibit
      the DNA synthesis of the small cells. Thus, only TGF-beta could completely
      inhibit both the DNA synthesis of any type of hepatocyte and the formation of
      small-cell colonies.

PMID- 7641303
TI  - Synthesis of toddacoumaquinone, a coumarin-naphthoquinone dimer, and its
      antiviral activities.
AB  - Toddacoumaquinone (1), a coumarin-naphthoquinone dimer, was synthesized through
      Diels-Alder reaction between 8-(1-acetoxy-3-methyl-1,3-butadienyl)-5,7
      dimethoxycoumarin (15) and 2-methoxy-1,4-benzoquinone (5). The activities of 1
      against several viruses were examined. A weak activity (EC50 = 10 micrograms/ml)
      was observed against HSV-1 and HSV-2, but no activity was seen against HIV-1.

PMID- 7641302
TI  - Physical-chemistry characteristics and biodistribution of poly(ethylene glycol)
      coated liposomes using poly(oxyethylene) cholesteryl ether.
AB  - Poly(ethylene glycol)-coated liposomes were prepared with poly(oxyethylene)
      cholesteryl ethers (mPEG-Chol). PEG unit numbers tested were 50, 100 and 200, of
      which the average molecular weights (m) of PEG were 2200, 4400 and 8800,
      respectively. Properties of both PEG-coated liposomes and PEG-Chol molecules were
      investigated. These liposomes exhibited a long circulation time in the blood
      after i.v. injection in rats, estimated by both the lipid membrane marker, L
      alpha-dipalmitoylphosphatidylcholine [2-palmitoyl-9,10-3H](3H-DPPC), and an
      internal aqueous marker, 3H-inulin. Accumulation in the liver and spleen at 8h
      post-injection was significantly reduced compared with conventional liposomes.
      The percentage of PEG-Chol incorporation in liposomal membranes was also
      investigated. Liposomes composed of egg yolk phosphatidylcholine (EPC)/PEG-Chol
      at various molar ratios were separated from free PEG-Chol molecules, which are
      not incorporated in liposomal membranes by chromatography over Sepharose CL-4B
      columns, PEG-Chol incorporation reached approx. 14 and 18 mol% of the total
      lipids with 25% PEG-Chol unit numbers of 200 and 50, respectively. The occupied
      area per molecule of PEG-Chol was larger than that of Chol, and the fluorescence
      anisotropy (r) of the initial 25 mol% (8800)PEG-Chol liposomes was smaller than
      that observed for 12.5 mol% Chol liposomes. PEG-coated liposomes containing
      calcein were incubated at 37 degrees C in heat-inactivated fetal bovine serum
      (FBS). In the presence of FBS, calcein leakage was increased with PEG-Chol
      percentage incorporation and an increase in FBS concentration. The amount
      released from PEG-coated liposomes represented 60% at maximum and was larger than
      that of the control liposomes. PEG-Chol molecules are interesting compounds since
      they can be easily synthesized in a large amount on an industrial scale. The
      basic physical-chemistry characteristics investigated in this article are
      critical to assess the pharmacological application of PEG-Chol liposomes as drug
      delivery systems.

PMID- 7641305
TI  - Degradation kinetics of the new antibacterial fluoroquinolone derivative,
      orbifloxacin, in aqueous solution.
AB  - The degradation kinetics of orbifloxacin [1-cyclopropyl-5,6,8-trifluoro-1,4
      dihydro-7-(cis-3,5-dimethyl-1-pipe raz inyl)-4-oxoquinoline-3-carboxylic acid]
      was investigated as a function of pH (1.5-10.5), temperature (100-120 degrees C)
      and buffer concentration (0.05-0.2 M) by means of high-performance liquid
      chromatography. The degradation of orbifloxacin in aqueous solution followed
      apparent first-order kinetics under all experimental conditions. No appreciable
      effect of buffer on the degradation of orbifloxacin was observed for any of the
      buffer species used in this study. The log k-pH profiles indicated specific-acid
      and specific-base catalyses and there were inflection points near pH 6 and 9
      corresponding to the pKa1 and pKa2 values. From the Arrhenius plots, the
      activation energies for k'H, k'H2O, kH2O, k"H2O and k"OH were found to be 31.9,
      36.9, 23.5, 26.5 and 19.0 kcal/mol, respectively. Arrhenius data obtained from
      this study showed that the degradation of orbifloxacin at room temperature was
      negligible at all pH values studied conditions (pH 1.5-10.5).

PMID- 7641304
TI  - Studies on new phosphodiesterase inhibitors. I. Synthesis of 1-(2,3-epoxypropoxy)
      2(4)-fluorobenzenes and 1-(2-hydroxy-3-morpholinopropoxy and
      piperazino)fluorobenzene derivatives.
AB  - A series of 1-(2,3-epoxypropoxy)-2(4)-fluorobenzenes and their corresponding 1-(2
      hydroxy-3-morpholinopropoxy and piperazino)fluorobenzene derivatives (8a--f) were
      synthesised via a short synthetic route in good chemical yields and were
      evaluated for inotropic and chronotropic activity in isolated guinea-pig atria
      preparation. The compounds act as potential phosphodiesterase (PDE) inhibitors
      with desirable biological activity and have considerable promise in heart
      therapy.

PMID- 7641306
TI  - Resistance of highly branched (1-->3)-beta-D-glucans to formolysis.
AB  - Small molecular weight (MW) glucan derivatives could be a useful tool for
      studying the mechanisms of beta-glucan mediated biological activity, especially
      as antagonists for a beta-glucan receptor. This paper described the stability of
      various (1-->6) branched (1-->3)-beta-D-glucans to formolysis in the preparation
      of small MW derivatives. The glucans used were curdlan (linear), pachyman (few
      branches), GRN (one branch in every third main chain unit; 2/6), SPG (2/6), SSG
      (3/6), and OL-2 (4/6). Curdlan and pachyman were easily degraded to
      oligosaccharides by degradation for 20 min at 100 degrees C by 90% formic acid.
      However, branched glucans, especially the highly branched glucans, SSG and OL-2,
      were significantly resistant to degradation, and the majority remained high MW.
      SSG required a longer period and/or a higher temperature (121 degrees C
      treatment) to produce small MW derivatives. Branched glucans were also resistant
      to zymolyase (an endo-(1-->3)-beta-D-glucan hydrolase) digestion. These facts
      suggest that the (1-->6)-beta-D-branched residues contribute to the glucans'
      resistance to formic acid degradation and zymolyase digestion.

PMID- 7641307
TI  - A novel resin glycoside, merremin (tuguajalapin X dimer), from Merremia
      hungaiensis.
AB  - A novel resin glycoside, merremin (1), has been isolated from the root of
      Merremia hungaiensis (Convolvulaceae). The structure has been determined to be an
      ester-type dimer of tuguajalapin X (2) on the basis of chemical and spectral
      data.

PMID- 7641308
TI  - Comparative catalytic activity of hemin and hematin in the breakdown of
      methyllinoleate hydroperoxide and peroxidation of methyllinoleate in methanol.
AB  - The breakdown of methyllinoleate hydroperoxide (LOOH) and peroxidation of
      methyllinoleate (LH) catalyzed by hemin and hematin were studied in 98% methanol.
      Spectrophotometry was used to follow the breakdown of LOOH. The peroxidation
      process of LH was monitored by the oxygen consumption. The pKa for the conversion
      of hemin to hematin was determined as 7.3 in 98% methanol. The catalytic rates
      for both processes were found to reach a maximum at pH 8 where about 80% of hemin
      was in the hematin form. This could be accounted for by the acceleration of the
      breakdown of LOOH due to binding of hydroxide or methoxide ion to the hemin iron.
      The reduction in the catalytic activity at a higher pH, where 100% of hemin was
      in the hematin form, however, suggested that H+ was also necessary. We propose a
      new scheme which shows the role of H+ and OH- (or CH3O-) together with ferryl
      iron in the catalytic process. The breakdown of hemin itself was also observed
      and its catalytic cycle number was estimated as 9. The gradual decomposition of
      hemin suggests involvement of a Fenton-type mechanism as a minor catalytic
      process.

PMID- 7641309
TI  - Fungal metabolites. XIX. Structural elucidation of channel-forming peptides,
      trichorovins-I-XIV, from the fungus Trichoderma viride.
AB  - Trichorovins (TV)-I-XIV are new antibiotic peptides obtained from conidia of the
      fungus Trichoderma viride. The peptide mixture of TVs was repeatedly fractionated
      by preparative HPLC until individual TVs showed a single peak on their analytical
      HPLC chromatograms. Nevertheless, FAB-MS or NMR indicated that each of TVs-I-XIV
      was composed of at least two components. We attempted to elucidate their
      structures within the fractions by electrospray ionization (ESI)-MS, FAB-MS, FAB
      MS/MS and NMR. TVs generally have molecular weights of approximately 1100-1200
      Da, and are characterized by an acetylated N-terminus, the presence of an
      aminoalcohol, e.g. leucinol, isoleucinol or valinol, at the C-terminus, and
      eleven residues including three alpha-aminoisobutyric acids in the molecule.
      Thus, it was determined that TVs belong to the class of peptaibols.

PMID- 7641310
TI  - Inhibitory effects of perillosides A and C, and related monoterpene glucosides on
      aldose reductase and their structure-activity relationships.
AB  - Monoterpene glucosides, perillosides A and C, obtained from the leaves of Perilla
      frutescens, were found to be inhibitors of aldose reductase (EC 1.1.1.21) which
      is considered to be a key enzyme in diabetic complications such as cataract. The
      apparent type of inhibition of rat lens aldose reductase by perillosides A and C
      was competitive with respect to glyceraldehyde and their K(i) values were 1.4 x
      10(-4) and 2.3 x 10(-4) M, respectively. The type of inhibition by their
      tetraacetates was non-competitive with respect to the same substrate, although
      their inhibitory effects were increased by about one order of magnitude compared
      with those of the perilllosides and the K(i) values were 2.5 x 10(-5) and 7.1 x
      10(-5) M, respectively. We also prepared related monoterpene glucosides and their
      tetraacetates and determined their inhibitory activities towards aldose reductase
      in order to elucidate the relationship between structure and inhibitory activity.

PMID- 7641311
TI  - Studies on the preparation of bioactive lignans by oxidative coupling reaction.
      V. Oxidative coupling reaction of methyl (E)-3-(2-hydroxyphenyl)propenoate
      derivatives and lipid peroxidation inhibitory effects of the produced lignans.
AB  - The oxidative coupling reactions of 2-hydroxycinnamates were investigated as a
      continuation of our previous studies on 4-hydroxy derivatives. The reaction of 2
      hydroxycinnamate 1 and 2-hydroxy-4-methoxycinnamate 3 with silver oxide afforded
      polymerized lignin-like products, while that of 2-hydroxy
      bis(methoxymethoxy)cinnamates 5 and 6, after acetylation, gave the enol acetates,
      8 and 14, of oxotetrahydrobenzoxanthene derivatives, respectively. These two
      products were also obtained by the oxidation of 5 and 6 with potassium
      hexacyanoferrate(III). In the reactions of 5 and 6 with iron(III) chloride, the
      major products were the partially demethoxymethoxylated compounds 9 and 15,
      respectively. Thus, the course of the reactions in the oxidation of 2
      hydroxycinnamates is quite different from that in the case of 4-hydroxy
      derivatives. The product 8 and the corresponding oxotetrahydrobenzoxanthene
      derivative were found to show moderate inhibitory effects upon lipid
      peroxidation.

PMID- 7641312
TI  - Alpha 1-adrenoceptor reagents. Synthesis of some 5,6,11,11a-tetrahydro-1H
      imidazo[1',5':1,6]pyrido and 5,6,11,11b-tetrahydro-1H
      imidazo[1',5':1,2]pyrido[3,4-b]indole-1,3(2H) -diones.
AB  - Several 2-substituted 5,6,11,11a-tetrahydro-1H-imidazo[1',5':1,6]pyrido (1) and
      5,6,11,11b-tetrahydro-1H-imidazo [1',5':1,2]pyrido[3,4-b]indole,3(2H)-diones (2)
      were synthesized and studied by 2D-NMR spectroscopy and difference nuclear
      Overhauser effect experiments. All the compounds were evaluated for in vitro
      alpha(1) adrenoceptor affinity by radioligand receptor binding assays. The most
      active derivative in displacement of [3H]prazosin from rat cortical membranes was
      1b (K(i) = 219 nM). At 1 microM concentration, compounds 1 and 2 had no effect on
      the benzodiazepine or 5-HT(1A) receptor. The biological activity profile of 1b
      makes it a possible lead compound for the design of new selective alpha1
      adrenoceptor ligands.

PMID- 7641313
TI  - Studies on cerebral protective agents. VII. Synthesis of novel 4-arylazole
      derivatives with anti-anoxic activity.
AB  - Novel 4-arylazole (i.e. thiazole, oxazole, and imidazole) derivatives, possessing
      an amino moiety at the C-5 position of the azole ring, were prepared and tested
      for anti-anoxic (AA) activity in mice. Among them, 5-(4-methylpiperazin-1
      yl)methyl-4-(3-nitrophenyl)-2-phenylthia zole (3b, FR75094) possessed significant
      AA activity (10 mg/kg, i.p. and 100 mg/kg, p.o., respectively), and was also
      effective on anti-lipid peroxidation (ALP) assay and inhibited arachidonate
      induced cerebral edema in rats. Structure-activity relationships in regard to AA
      activity of this series of compounds are discussed.

PMID- 7641314
TI  - Synthesis, antiviral, antibacterial and antitumor cell activities of 2'-deoxy-2'
      fluoropuromycin.
AB  - A procedure for the synthesis of 2'-deoxy-2'-fluoropuromycin (1b) was developed.
      Ring opening of the lyxo-epoxide (4) or nucleophilic displacement of the 3'-O
      mesylate (5) by an azide ion afforded two azido nucleosides, 6a and 7a. The major
      product (7a) was reacted with diethylaminosulfur trifluoride (DAST) to give the
      2'-fluoronucleoside (8), which was converted to the 3'-aminonucleoside (9) by
      hydrogenation. Compound 9 was condensed with an amino acid by the conventional
      method and subsequently deprotected by acid to give 1b. Compounds 1b, 6b and 7b
      exhibited no selective antiviral activity against several DNA and RNA viruses.
      Compound 1b had weak antibacterial activity (minimum inhibitory concentration
      approximately 25-50 micrograms/ml) and was cytotoxic to several tumor cell lines
      (L1210, Molt 4, CEM) at a concentration of about 5 microM. This antitumor cell
      activity may be attributed to inhibition of protein biosynthesis.

PMID- 7641316
TI  - Studies on the constituents of Polygala japonica HOUTT. II. Structures of
      polygalasaponins XI-XIX.
AB  - Nine new oleanane-type saponins polygalasaponins XI-XIX were isolated from the
      aerial part of Polygala japonica. The structures of these compounds were
      established on basis of spectroscopic and chemical evidence.

PMID- 7641315
TI  - Synthesis and evaluation of novel pyrazolo[1,5-alpha]pyrimidine derivatives as
      nonpeptide angiotensin II receptor antagonists.
AB  - A novel series of 6-alkyl-7-oxo-4,7-dihydropyrazolo[1,5-alpha]pyrimidine-3
      carboxyli c acid derivatives was prepared as angiotensin II (AII) receptor
      antagonists. When evaluated in an in vitro binding assay using COS cells
      transfected with a cDNA encoding a human AT1 angiotensin II receptor, the
      compounds in this series showed Ki values in the range of 0.4-4.0 nM. In
      anesthetized spontaneously hypertensive rats (SHRs), administration of the 6
      propyl derivative 4d (1 mg/kg, i.v.) reduced the mean blood pressure (MBP) by a
      maximum of more than 30 mmHg from the normal value.

PMID- 7641317
TI  - Structures of steroidal saponins from the tubers of Brodiaea californica and
      their inhibitory activity on tumor promoter-induced phospholipid metabolism.
AB  - Phytochemical examination of the fresh tubers of Brodiaea californica resulted in
      the isolation of four new steroidal saponins. Their structures were determined,
      by extensive spectral analysis including two-dimensional (2D) NMR spectroscopy
      and acid-catalyzed hydrolysis, to be (25S)-spirost-5-ene-1 beta,3 beta-diol
      [(25S)-ryscogenin] 1-O-[O-beta-D-glucopyranosyl-(1-->3)-O-alpha-L-rhamnopyranosyl
      (1-->2)- beta-D-glucopyranoside] (1), (25S)-ruscogenin 1-O-[O-beta-D
      glucopyranosyl-(1-->3)-O-alpha-L-rhamnopyranosyl-(1-->2)-O -[beta-D-xylopyranosyl
      (1-->3)]-beta-D-glucopyranoside] (2), the C-20 and C-22 isomer of 2 (3) and the
      6'-O-acetyl derivative of 2 (4), respectively. The conformations of the
      tetrasaccharide moiety of 2 and 4 were inspected through molecular mechanics and
      molecular dynamics calculation studies, showing that the acetyl group attached to
      C-6 of the inner glucose was near the C-21 methyl of the aglycon in the
      calculated preferred conformation of 4, which must cause the downfield shift of
      21-Me by 0.07 ppm in comparing the 1H-NMR of 4 with that of 2. The inhibitory
      activity of the isolated saponins on 12-O-tetradecanoylphorbor-13-acetate (TPA)
      stimulated 32P-incorporation into phospholipids of HeLa cells was evaluated to
      identify new antitumor-promoter compounds.

PMID- 7641318
TI  - The intima. Soil for atherosclerosis and restenosis.

PMID- 7641319
TI  - Characterization of 5' end of human thromboxane receptor gene. Organizational
      analysis and mapping of protein kinase C--responsive elements regulating
      expression in platelets.
AB  - Platelet thromboxane receptors are acutely and reversibly upregulated after acute
      myocardial infarction. To determine if platelet thromboxane receptors are under
      transcriptional control, we isolated and characterized human genomic DNA clones
      containing the 5' flanking region of the thromboxane receptor gene. The exon
      intron structure of the 5' portion of the thromboxane receptor gene was
      determined initially by comparing the nucleotide sequence of the 5' flanking
      genomic clone with that of a novel human uterine thromboxane receptor cDNA that
      extended the mRNA 141 bp further upstream than the previously identified human
      placental cDNA. A major transcription initiation site was located in three human
      tissues approximately 560 bp upstream from the translation initiation codon and
      380 bp upstream from any previously identified transcription initiation site. The
      thromboxane receptor gene has neither a TATA nor a CAAT consensus site. Promoter
      function of the 5' flanking region of the thromboxane receptor gene was evaluated
      by transfection of thromboxane receptor gene promoter/chloramphenicol
      acetyltransferase (CAT) chimera plasmids into platelet-like K562 cells.
      Thromboxane receptor promoter activity, as assessed by CAT expression, was
      relatively weak but was significantly enhanced by phorbol ester treatment.
      Functional analysis of 5' deletion constructs in transfected K562 cells and gel
      mobility shift localized the major phorbol ester-responsive motifs in the
      thromboxane receptor gene promoter to a cluster of activator protein-2 (AP-2)
      binding consensus sites located approximately 1.8 kb 5' from the transcription
      initiation site. These studies are the first to determine the structure and
      organization of the 5' end of the thromboxane receptor gene and demonstrate that
      thromboxane receptor gene expression can be regulated by activation of protein
      kinase C via induction of an AP-2-like nuclear factor binding to upstream
      promoter elements. These findings strongly suggest that the mechanism for
      previously described upregulation of platelet thromboxane receptors after acute
      myocardial infarction is increased thromboxane receptor gene transcription in
      platelet-progenitor cells.

PMID- 7641320
TI  - Endothelium-specific in vivo gene transfer.
AB  - Targeted expression of genetic material within the vascular endothelium is
      potentially a powerful tool for the investigation of endothelial cell (EC)
      biology. We developed, optimized, and characterized an efficient somatic
      transgenic model of EC-specific gene transfer. Rat carotid arteries were infused
      with adenovirus expressing a beta-galactosidase (beta-gal) gene. The level and
      cell-type specificity of recombinant gene expression were measured by assaying
      beta-gal activity in vessel extracts and by counting transduced cells in
      histological sections. Toxicity was evaluated by counting total ECs (3 days) and
      by measuring neointimal formation (14 days). Effects of transduction on the
      proliferation of vascular cells were measured with bromodeoxyuridine and
      [3H]thymidine. Maximum recombinant gene expression resulted from infusion of 1 x
      10(10) to 1 x 10(11) plaque-forming units (pfu) per milliliter; approximately 35%
      of luminal ECs were transduced. A high degree of EC specificity (90% to 98% of
      total transduced cells) was maintained over this range of virus concentrations.
      More highly concentrated virus resulted in loss of beta-gal expression and a
      large decrease in luminal EC number (97% decrease, P < .001). Gene transfer at 4
      x 10(10) pfu/mL was efficient, preserved EC integrity, and caused minimal
      neointimal formation. After gene transfer, there were early (3-day) increases in
      both EC and smooth muscle cell proliferation. At 14 days, only EC proliferation
      remained elevated (18% versus 1.4% in vehicle-infused arteries, P = .005). This
      animal model permits efficient highly EC-specific gene transfer. Vascular
      toxicity is minimal, although the EC proliferative index is elevated. This model
      will be useful in experiments that elucidate the biological role of EC gene
      products and define pathways of EC gene regulation and signal transduction in
      vivo.

PMID- 7641321
TI  - Thrombin regulates expression of monocyte chemoattractant protein-1 in vascular
      smooth muscle cells.
AB  - Thrombin, a serine protease generated at sites of vascular injury, plays a role
      in the pathogenesis of atherosclerosis and restenosis after angioplasty.
      Adherence of monocytes to the endothelium and migration into the subendothelial
      space is an important early event in the pathogenesis of atherosclerosis.
      Monocyte chemoattractant protein 1 (MCP-1) may be an important mediator of
      monocyte recruitment to the tissue in this and other diseases. We have
      characterized the expression of MCP-1 in vascular smooth muscle cells (VSMCs)
      isolated from human renal artery and studied its regulation by thrombin. Serum
      deprived cells release monocyte chemotactic activity that is neutralized (80%) by
      an MCP-1 antibody. The antibody recognized a 13- and 15-kD protein in smooth
      muscle cell-conditioned medium. Thrombin stimulates MCP-1 gene expression in a
      concentration- and time-dependent manner. An increase over basal levels was
      observed with concentrations of thrombin as low as 0.05 U/mL. The maximal effect
      occurred at 5 U/mL. The stimulatory effect was detected within 1 hour, reached a
      maximum at 3 hours, and was still present at 8 to 24 hours after the addition of
      thrombin. A concentration- and time-dependent effect of thrombin on MCP-1 gene
      expression was also found in rat VSMCs. The thrombin protease inhibitor hirudin
      blocked thrombin-induced MCP-1 expression. Thrombin stimulated the release of MCP
      1 protein in conditioned medium of human VSMCs as measured by radioimmunoassay
      and chemotactic assay. Thrombin also increased monocyte chemotactic activity in
      short-term organ cultures of rat aortic rings and in first passage
      cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7641322
TI  - Epidermal growth factor receptor-targeted cytotoxin inhibits neointimal
      hyperplasia in vivo. Results of local versus systemic administration.
AB  - Smooth muscle cell accumulation is a key feature of restenosis that may be
      inhibited by the delivery of receptor-targeted cytotoxins. DAB389EGF is a
      recombinant fusion protein in which the receptor-binding domain of diphtheria
      toxin has been replaced by human epidermal growth factor (EGF). We investigated
      the effectiveness of DAB389EGF to inhibit neointimal hyperplasia in the balloon
      injured rat carotid artery. Incubation of rat carotid arteries with 125I-labeled
      EGF revealed extensive EGF binding sites in the neointima of balloon-injured
      arteries. Sixty rats subsequently received either saline or DAB389EGF (total
      dose, 0.15 mg) delivered immediately following balloon injury either
      systemically, via 14-day continuous osmotic pump infusion, or locally, via 30
      minute intraluminal incubation. The effect of both treatment strategies was
      measured 2 weeks after injury by cross-sectional morphometric analysis of intimal
      area, the ratio of intimal/medial area (I/M), and the percent luminal narrowing
      (%LN). In addition, proliferative activity was assessed by immunostaining for the
      presence of the proliferating cell nuclear antigen (PCNA). Compared with
      controls, systemic delivery of fusion toxin significantly reduced intimal area,
      I/M, and %LN by 40%, 40%, and 29%, respectively. However, these rats exhibited 2%
      weight loss, indicating mild systemic toxicity. Local, intraluminal
      administration of DAB389EGF yielded a more pronounced reduction in intimal area,
      I/M, and %LN by 74%, 79%, and 72%, respectively. This inhibitory effect was
      preserved at 3 weeks postinjury, and PCNA immunostaining of locally treated
      arteries revealed a virtual absence of proliferative activity in the neointima
      and media at this timepoint. In contrast to systemically treated rats, rats
      receiving fusion toxin locally gained weight at a rate similar to controls,
      indicating avoidance of systemic toxicity. We conclude that DAB389EGF is a potent
      inhibitor of neointimal hyperplasia in vivo and that whereas an inhibitory effect
      may be achieved by systemic delivery, local delivery appears to be more potent,
      avoids systemic toxicity, and thus represents a feasible strategy to preempt
      restenosis.

PMID- 7641323
TI  - Elevated levels of cAMP inhibit protein kinase C--independent mechanisms of
      endothelial platelet-derived growth factor-B chain and intercellular adhesion
      molecule-1 gene induction by lysophosphatidylcholine.
AB  - Lysophosphatidylcholine (lyso-PC), a polar phospholipid product increased in
      atherogenic lipoproteins and atherosclerotic lesions, has been shown to
      differentially induce functional intercellular adhesion molecule-1 (ICAM-1) and
      vascular cell adhesion molecule-1 and mRNA for platelet-derived growth factor
      (PDGF)-A and -B chains and heparin-binding epidermal growth factor-like growth
      factor in various cultured endothelial cells. In this study, we have demonstrated
      increased expression of cell- and matrix-associated forms of PDGF-B chain (PDGF
      B) protein elicited by lyso-PC and further characterized potential signal
      transduction mechanisms responsible for lyso-PC-induced gene expression, focusing
      on PDGF-B and ICAM-1 genes in cultured human umbilical vein endothelial cell
      models. Cycloheximide almost completely inhibited PDGF-B but not ICAM-1 mRNA
      induction elicited by lyso-PC, suggesting that dependence on de novo protein
      synthesis for PDGF-B is different from that for ICAM-1. Prolonged exposure to
      phorbol myristate acetate (PMA), which depletes protein kinase C (PKC), or
      staurosporine, a PKC inhibitor, did not block lyso-PC-induced increases in PDGF-B
      or ICAM-1 mRNA. Forskolin and dibutyryl cAMP, which elevate intracellular cAMP
      levels, blocked both PDGF-B and ICAM-1 upregulation elicited by lyso-PC; however,
      these cAMP-elevating agents did not suppress ICAM-1 upregulation by PMA. Taken
      together, PDGF-B and ICAM-1 gene induction by lyso-PC may involve different
      signaling mechanisms; however, both appear to be independent of PMA-regulatable
      PKC activation but are suppressed by increased levels of intracellular cAMP.

PMID- 7641324
TI  - Some growth factors stimulate cultured adult rabbit ventricular myocyte
      hypertrophy in the absence of mechanical loading.
AB  - Cultured adult rabbit cardiac myocytes treated with recombinant growth factors
      display enhanced rates of protein accumulation (ie, growth) in response to
      insulin and insulin-like growth factors (IGFs), but epidermal growth factor,
      acidic or basic fibroblast growth factor, and platelet-derived growth factor
      failed to increase contractile protein synthesis or growth of the heart cells.
      Insulin and IGF-1 increased growth rates by stimulating anabolic while
      simultaneously inhibiting catabolic pathways, whereas IGF-2 elevated growth
      modestly by apparently inhibiting lysosomal proteolysis. Neutralizing antibodies
      directed against either IGF-1 or IGF-2 or IGF binding protein 3 blocked protein
      accumulation. A monoclonal antibody directed against the IGF-1 receptor also
      inhibited changes in protein turnover provoked by recombinant human IGF-1 but not
      IGF-2. Of the other growth factors tested, only transforming growth factor-beta 1
      increased the fractional rate of myosin heavy chain (MHC) synthesis, with beta
      MHC synthesis being elevated and alpha-MHC synthesis being suppressed. However,
      the other growth factors were able to modestly stimulate the rate of DNA
      synthesis in this preparation. Bromodeoxyuridine labeling revealed that these
      growth factors increased DNA synthesis in myocytes and nonmyocytes alike, but the
      heart cells displayed neither karyokinesis or cytokinesis. In contrast,
      cocultures of cardiac myocytes and nonmyocytes and nonmyocyte-conditioned culture
      medium failed to enhance the rate of cardiac MHC synthesis or its accumulation,
      implying that quiescent heart cells do not respond to "conditioning" by cardiac
      nonmyocytes. These findings demonstrated that insulin and the IGFs promote
      passively loaded cultured adult rabbit heart cells to hypertrophy but suggest
      that other growth factors tested may be limited in this regard.

PMID- 7641325
TI  - Cl- -HCO3- exchange in developing neonatal rat cardiac cells. Biochemical
      identification and immunolocalization of band 3-like proteins.
AB  - The Cl- -HCO3- exchanger is the main anionic exchanger (AE) that alleviates
      alkaline loads in cardiac cells. We recently identified in adult ventricular
      cells two membrane proteins (80 and 120 kD) immunologically related to the
      erythroid band 3 and likely to mediate the anion exchange. In the present study,
      we further investigated the Cl- -HCO3- exchanger activity concomitantly with the
      expression and intracellular localization of the band 3-like proteins during the
      development of neonatal rat cardiac cells maintained in culture for 17 days.
      Microspectrofluorometric measurements of pHi in single cells show that neonatal
      rat cardiomyocytes display a fully functional DIDS-sensitive Cl- -HCO3- exchanger
      at early stages of development. Neither basal pHi nor the anion exchange activity
      changes with different stages of the culture. In Western blotting with an anti
      whole erythroid band 3 antibody, we found both the 80- and the 120-kD band 3-like
      proteins in whole heart and cultured neonatal cardiac cells. The 80-kD protein
      was also recognized by an anti-AE1 antiserum, whereas the 120-kD protein was
      specifically detected by an anti-cardiac AE3 antibody. Thus, we propose that the
      proteins are encoded by two different genes, AE1 and AE3, respectively.
      Subcellular fractionation of isolated and cultured cardiomyocytes revealed the
      presence of both proteins in the membrane, nuclear, and myofibril fractions. The
      results obtained in biochemical experiments corroborate the confocal images of
      immunostained neonatal cells, which demonstrate perinuclear location of band 3
      like proteins at an early stage of development and their appearance within
      myofilaments after cell maturation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7641326
TI  - beta-Adrenergic stimulation induces acetylcholine to activate ATP-sensitive K+
      current in cat atrial myocytes.
AB  - Our previous work on atrial myocytes suggested that the effect of acetylcholine
      (ACh) to increase K+ conductance can be potentiated by prior loading of the
      sarcoplasmic reticulum (SR) with Ca2+. The present study, therefore, sought to
      determine whether prior exposure to isoproterenol (ISO) potentiates ACh-induced
      increases in K+ conductance and the underlying mechanisms. A nystatin-perforated
      patch whole-cell configuration was used to record from cat atrial myocytes.
      Voltage-clamp ramps (40 mV/s) were used to assess total membrane conductance. The
      experimental protocol consisted of two consecutive 30-second ACh exposures (ACh1
      and ACh2) separated by a 6-minute recovery period in ACh-free solution. In
      general, experimental interventions, such as exposure to ISO, were imposed during
      the period between ACh1 and ACh2 to determine their effects on the response to
      ACh2 in relation to ACh1. Under control conditions, K+ conductances induced by
      ACh1 and ACh2 were not different from one another with or without activation of L
      type Ca2+ current (ICa,L) during the recovery period. When 1 mumol/L ISO plus
      ICa,L activation was imposed during the recovery period, ACh2 induced a
      significantly larger increase in K+ conductance than ACh1. The ACh2-induced K+
      current potentiated by ISO was time independent and selectively blocked by 10
      mumol/L glibenclamide and therefore identified as ATP-sensitive K+ current
      (IK,ATP). The effect of ISO to induce ACh2-activated IK,ATP was mimicked by 1
      mumol/L forskolin or 200 mumol/L 8-(4-chlorophenylthio)-cAMP, but not by 0.5
      mumol/L BAY K 8644, and was selectively abolished by (1) 5 mumol/L thapsigargin
      or 1 mumol/L ryanodine, agents that prevent accumulation of SR Ca2+, (2)
      inhibition of L-type Ca2+ current (ICa,L) by 1 mumol/L nisoldipine or zero
      external Ca2+, (3) 50 mumol/L Rp-cAMPs, an inhibitor of cAMP-dependent protein
      kinase A, or (4) 2 mumol/L propranolol. Atropine (1 mumol/L) abolished all ACh
      induced currents. Moreover, ACh2-activated IK,ATP was selectively blocked by 0.2
      mumol/L pirenzepine, an M1 muscarinic receptor antagonist, or 0.1 mumol/L
      calphostin C, a selective inhibitor of protein kinase C. AFDX116 (100 mumol/L),
      an M2 muscarinic receptor antagonist, blocked the conventional ACh-activated K+
      current and revealed ACh2-activated IK,ATP. These results indicate that prior
      exposure to ISO potentiates ACh-induced increases in K+ current via ACh-activated
      IK,ATP.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7641327
TI  - Determinants of antiarrhythmic drug action. Electrostatic and hydrophobic
      components of block of the human cardiac hKv1.5 channel.
AB  - The molecular basis of antiarrhythmic drug action is still poorly understood. We
      recently reported that block of the human cardiac hKv1.5 channel by quinidine
      displayed similarity with internal quaternary ammonium block of squid and Shaker
      potassium channels. To gain further insight into the molecular determinants of
      the affinity and the stereoselectivity of antiarrhythmic drug action, we studied
      the effects of quinine (a diastereomer of quinidine), clofilium (a quaternary
      ammonium class III agent), and tetrapentylammonium (TPeA, a biophysical reference
      probe for the internal quaternary ammonium binding site). For all compounds,
      block was voltage dependent, with a steep increase over the voltage range of
      channel opening and a superimposed weaker voltage dependence at more positive
      potentials. The latter electrostatic component was similar for all drugs,
      consistent with a binding reaction sensing approximately 20% of the transmembrane
      electrical field. Clofilium and TPeA displayed a higher apparent affinity (0.15
      and 0.28 mumol/L, respectively), and quinine displayed a lower one (21 mumol/L)
      compared with quinidine (6.2 mumol/L). Block development upon depolarization was
      time dependent for clofilium and TPeA but slow compared with quinidine. A time
      dependent component was difficult to resolve for quinine, but the time course of
      deactivating tail currents was slower than in the control condition. The
      resulting crossover phenomenon was also observed for the quaternary drugs.
      Compared with TPeA alone, the combined application of quinine and TPeA resulted
      in a reduced current that decayed slower, consistent with competition.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7641328
TI  - On the molecular nature of the lidocaine receptor of cardiac Na+ channels.
      Modification of block by alterations in the alpha-subunit III-IV interdomain.
AB  - The mechanism of inhibition of Na+ channels by lidocaine has been suggested to
      involve low-affinity binding to rested states and high-affinity binding to the
      inactivated state of the channel, implying either multiple receptor sites or
      allosteric modulation of receptor affinity. Alternatively, the lidocaine receptor
      may be guarded by the channel gates. To test these distinct hypotheses,
      inhibition of Na+ channels by lidocaine was studied by voltage-clamp methods in
      both native and heterologous expression systems. Native Na+ channels were studied
      in guinea pig ventricular myocytes, and recombinant human heart Na+ channels were
      expressed in Xenopus laevis oocytes. Fast inactivation was eliminated by mutating
      three amino acids (isoleucine, phenylalanine, and methionine) in the III-IV
      interdomain to glutamines or by enzymatic digestion with alpha-chymotrypsin. In
      channels with intact fast inactivation, lidocaine block developed with a time
      constant of 589 +/- 42 ms (n = 7) at membrane potentials between -50 and +20 mV,
      as measured by use of twin pulse protocols. The IC50 was 36 +/- 1.8 mumol/L.
      Control channels inactivated within 20 ms, and slow inactivation developed much
      later (time constant of slow inactivation, 6.2 +/- 0.36 s). The major component
      of block developed long after activated and open channels were no longer
      available for drug binding. Control channels recovered fully from inactivation in
      < 50 ms at -120 mV (time constant, 11 +/- 0.5 ms; n = 50).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7641329
TI  - Optical transmembrane potential measurements during defibrillation-strength
      shocks in perfused rabbit hearts.
AB  - To study the optical transmembrane potential change (delta F) induced during
      shocks, optical recordings were obtained in 15 isolated perfused rabbit hearts
      treated with the potentiometric dye di-4-ANEPPS and diacetyl monoxime. Shock
      electrodes were sutured on the right and left ventricles. A laser beam 30 microns
      in diameter was used to optically excite di-4-ANEPPS. Fluorescence from a region
      150 microns in diameter was recorded during a shock. In the macroscopic study
      (six animals), there were nine recording spots that were 3 mm apart between the
      two shock electrodes. In the microscopic study, there were three recording
      regions that were 3 mm away from either shock electrode and midway between them,
      with nine recording spots that were 30 microns (three animals), 100 microns
      (three animals), and 300 microns (three animals) apart in each region. After 20
      S1 stimuli, a 10-ms truncated exponential S2 shock of defibrillation-threshold
      strength was given during the plateau of the last S1 action potential. In the
      microscopic study, shocks were also given during diastole, with delta F
      recordings at the three recording regions. Shocks of both polarities were tested.
      delta F during the shock was expressed as a percentage of the fluorescence change
      during the S1 upstroke action potential amplitude (the S1 Fapa), ie, delta
      F/Fapa%. In the macroscopic study, the magnitudes of delta F/Fapa% from recording
      spots 1 to 9, numbered from the left to the right ventricular electrodes, were 77
      +/- 41%, 46 +/- 32%, 32 +/- 27%, 28 +/- 20%, 37 +/- 25%, 24 +/- 20%, 33 +/- 22%,
      37 +/- 25%, and 59 +/- 29%, respectively (P < .05 among the nine spots).
      Depolarization or hyperpolarization could occur near either shock electrode with
      both shock polarities, but the magnitude of hyperpolarization was 1.8 +/- 0.9
      times that of depolarization at the same recording spot when the shock polarity
      was reversed (P < .01). In the microscopic study, the change in delta F/Fapa%
      varied significantly over the microscopic regions examined. The maximum values of
      delta F/Fapa% for hyperpolarizing shocks during diastole reached only 7 +/- 10%
      of those for shocks during the plateau (P < .01). During diastole, the time until
      a new action potential occurred after the beginning of the shock was shorter when
      the membrane was depolarized (1.1 +/- 0.5 ms) than when it was hyperpolarized
      (12.8 +/- 9.1 ms, P < .01). Conclusions are as follows: (1) A shock can induce
      either hyperpolarization or depolarization. (2) Hyperpolarization or
      depolarization during a shock can occur near either the anodal or cathodal shock
      electrode. (3) Variation of delta F/Fapa% exists within a microscopic
      region.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7641330
TI  - Reperfusion of rat heart after brief ischemia induces proteolysis of calspectin
      (nonerythroid spectrin or fodrin) by calpain.
AB  - Rat myocardium expresses the 240- and 235-kD polypeptides antigenically related
      to alpha- and beta-subunits of brain calspectin (nonerythroid spectrin or
      fodrin), respectively. In the subcellular fractions of the myocardium, alpha
      calspectin was found in the 600g, 10,000g, and 100,000g pellets, whereas beta
      calspectin was localized to the 10,000g pellet. On the basis of the Na+,K(+)
      ATPase activity and the contents of a gap junction protein, the sarcolemma was
      distributed to the 10,000g and 100,000g pellets, and the intercalated disks were
      enriched in the 10,000g pellet. Both alpha- and beta-calspectin were proteolyzed
      by calpain in vitro. The two subunits were also proteolyzed in vivo, when the rat
      hearts underwent 10 to 60 minutes of global ischemia followed by 30 minutes of
      reperfusion. The reperfusion following the ischemia induced the proteolysis of
      alpha-calspectin in the 10,000g and 100,000g pellets, producing the 150-kD
      fragment. A synthetic calpain inhibitor, calpain inhibitor-1, suppressed the
      degradation of calspectin in vivo, which indicates that calpain is responsible
      for the reperfusion-induced proteolysis of calspectin. The inhibitor also
      improved myocardial stunning. Immunohistochemical study revealed that the
      proteolysis of alpha-calspectin occurs at the intercalated disks and the
      sarcolemma after postischemic reperfusion, in accord with the biochemical data.
      These results suggest that degradation of calspectin partly accounts for the
      contractile failure of the myocardium after postischemic reperfusion by
      disrupting the membrane skeleton and the intercalated disks.

PMID- 7641331
TI  - Role of bradykinin in protection of ischemic preconditioning in rabbit hearts.
AB  - Bradykinin receptor activation has been proposed to be involved in ischemic
      preconditioning. In the present study, we further investigated the role of this
      agent in preconditioning in both isolated and in situ rabbit hearts. All hearts
      were subjected to 30 minutes of regional ischemia followed by reperfusion for 2
      hours (in vitro hearts) and 3 hours (in situ hearts). Infarct size was measured
      by tetrazolium staining and expressed as a percentage of the size of the risk
      zone. Preconditioning in situ hearts with 5 minutes of ischemia and 10 minutes of
      reperfusion significantly reduced infarct size to 10.2 +/- 2.2% of the risk
      region (P < .0005 versus control infarct size of 36.7 +/- 2.6%). Pretreatment
      with HOE 140 (26 micrograms/kg), a bradykinin B2 receptor blocker, did not alter
      infarct size in nonpreconditioned hearts (40.6 +/- 5.3% infarction) but abolished
      protection from ischemic preconditioning (34.1 +/- 1.6% infarction). However,
      when HOE 140 was administered during the initial reflow period following 5
      minutes of ischemia, protection was no longer abolished (15.6 +/- 3.9% infarction
      versus 13.3 +/- 3.8% without HOE 140, P = NS). Bradykinin infusion in isolated
      hearts mimicked preconditioning, and protection was not affected by pretreatment
      with the nitric oxide synthase inhibitor N omega-nitro-L-arginine methyl ester or
      the prostaglandin synthesis inhibitor indomethacin but could be completely
      abolished by the protein kinase C (PKC) inhibitors polymyxin B and staurosporine
      as well as by HOE 140. HOE 140 could not block the protection of ischemic
      preconditioning in isolated hearts. That failure was apparently due to the
      absence of blood-borne kininogens rather than autonomic nerves. When the
      preconditioning stimulus in the in situ model was amplified with four cycles of 5
      minute ischemia/10-minute reperfusion, HOE 140 pretreatment could no longer block
      protection (infarct size was 10.7 +/- 3.5% versus 6.4 +/- 2.0% without HOE 140, P
      = NS). We propose that bradykinin receptors protect by coupling to PKC as do
      adenosine receptors, and blockade of either receptor will diminish the total
      stimulus of PKC below threshold and prevent protection. A more intense
      preconditioning ischemic stimulus can overcome bradykinin receptor blockade,
      however, by simply enhancing the amount of adenosine and possibly other agonists
      released.

PMID- 7641332
TI  - Direct in vivo observation of subendocardial arteriolar response during reactive
      hyperemia.
AB  - To study the vasodilatory capacity of subendocardial (ENDO) arterioles, we
      evaluated the reactive hyperemic responses of ENDO as well as subepicardial (EPI)
      arterioles in 40 dogs by our needle-probe intravital microscope. We also examined
      the individual and combined effects of an ATP-sensitive K+ channel blocker
      (glibenclamide, 200 micrograms/kg), an inhibitor of nitric oxide synthase (NG
      monomethyl-L-arginine [L-NMMA], 2 mumol/min, 20 minutes), and an adenosine
      receptor antagonist (8-phenyltheophylline [8PT], 0.75 mumol/min, 15 minutes). The
      percent increase in end-diastolic diameter of ENDO arterioles was larger (P <
      .01) than that of EPI arterioles during reactive hyperemia, especially for the
      arterioles larger than 120 microns (P < .01). The diastolic-to-systolic vascular
      pulsation amplitude at the peak flow was greater in ENDO than EPI arterioles (25%
      versus 6%, P < .05). Compared with control conditions, the presence of both
      glibenclamide and L-NMMA suppressed the vasodilation responses of ENDO arterioles
      (P < .01 for both) and EPI arterioles (P < .05 for both). The effect of L-NMMA
      was greater in ENDO arterioles (P < .01), but that of glibenclamide was not
      different between ENDO and EPI arterioles. 8PT influenced the hyperemic response,
      although statistical significance was found only in the flow response. The effect
      of combined infusion of L-NMMA and glibenclamide with or without 8PT was greater
      than that of individual infusions in both ENDO and EPI arterioles. Conclusions
      are as follows: (1) The vasodilatory response of ENDO arterioles was even larger
      than that of EPI arterioles. Thus, the smaller flow reserve of ENDO arterioles
      may be caused by other factors, including the greater effects of myocardial
      compression and nitric oxide on the ENDO arterioles. (2) The vascular responses
      of ENDO and EPI arterioles were modulated by both endothelium-independent and 
      dependent vasodilative factors, and the effect of each factor including adenosine
      was associated with the effects of others.

PMID- 7641333
TI  - In vivo echocardiographic detection of enhanced left ventricular function in gene
      targeted mice with phospholamban deficiency.
AB  - We evaluated the ability of M-mode and Doppler echocardiography to assess left
      ventricular (LV) function reliably and repeatedly in mice and tested whether
      these techniques could detect physiological alterations in phospholamban (PLB)
      deficient mice. Anesthetized wild-type mice (n = 7) and mice deficient in PLB (n
      = 8) were studied with two-dimensional guided M-mode and Doppler echocardiography
      using a 9-MHz imaging and 5- to 7.5-MHz Doppler transducer. Data were acquired in
      the baseline state and after intraperitoneal isoproterenol administration (2.0
      micrograms/g IP). Interobserver and intraobserver variability and reproducibility
      were excellent. PLB-deficient mice were associated with significant (P < .05)
      increases in several physiological parameters (mean +/- SD) compared with wild
      type control mice: normalized mean velocity of circumferential shortening (7.7 +/
      2.1 versus 5.5 +/- 1.0 circ/sec), peak aortic velocity (105 +/- 13 versus 75 +/-
      9.2 cm/s), mean aortic acceleration (57 +/- 16 versus 31 +/- 4 m/s2), and peak
      early-diastolic transmitral velocity (80.0 +/- 7.2 versus 66.9 +/- 7.7 cm/s). LV
      dimensions, shortening fractions, heart rates, late diastolic transmitral (A)
      velocities, and early to late (E/A) diastolic velocity ratios were similar in
      both groups. Isoproterenol administration resulted in significant increases in
      Doppler indices of ventricular function in control but not PLB-deficient mice.
      These findings indicate that assessment of LV function can be performed
      noninvasively in mice under varying physiological conditions and that PLB
      regulates basal LV function in vivo.

PMID- 7641334
TI  - Hypoxia regulates vascular endothelial growth factor gene expression in
      endothelial cells. Identification of a 5' enhancer.
AB  - Vascular endothelial growth factor (VEGF) is a potent mitogen specific for
      endothelial cells. Its expression is dramatically induced by low oxygen tension
      in a variety of cell types, and it has been suggested to be a key mediator of
      hypoxia-induced angiogenesis. Although VEGF action is targeted to endothelial
      cells, it is generally believed that these cells do not express VEGF. In
      addition, the mechanisms by which hypoxia regulates VEGF production remain
      unclear. We report in the present study that pulmonary artery endothelial cells
      do not express VEGF under basal conditions; however, significant VEGF mRNA levels
      accumulate when these cells are exposed to hypoxia. Using a DNA fragment
      containing human VEGF promoter sequence, we identified a 28-bp element that is
      necessary and sufficient to upregulate transcription in response to hypoxia. This
      element can act as a hypoxia-specific enhancer when placed upstream or downstream
      from a heterologous promoter. The enhancer includes, in addition to an octamer
      homologous to the hypoxia-inducible factor-1 (HIF-1) consensus, a sequence that
      resides 3' to the consensus. Although this sequence may not be involved in the
      binding of HIF-1, it is absolutely required for the enhancer activity and may be
      the binding site for certain constitutive binding proteins. The expression of
      VEGF by endothelial cells in response to hypoxia may provide an important
      mechanism by which endothelial cell permeability and proliferation is regulated
      in an autocrine manner.

PMID- 7641335
TI  - Endogenous and exogenous nitric oxide protect against intracoronary thrombosis
      and reocclusion after thrombolysis.
AB  - BACKGROUND: Nitric oxide (NO), an endothelium-derived relaxing factor, plays an
      important role in regulating platelet activation. We evaluated the effect of NO
      in a canine model of intracoronary thrombosis, thrombolysis, and reocclusion.
      METHODS AND RESULTS: Before thrombosis was induced, 34 anesthetized dogs were
      treated with a continuous intracoronary infusion of saline (n = 8); NG-nitro-L
      arginine (L-NNA, n = 8), an inhibitor of NO synthetase; L-arginine (n = 7), the
      precursor for NO; or sodium nitroprusside (SNP, n = 11), an NO donor. Ten minutes
      after the infusion was begun, an electric current of 150 microA was applied to
      the endothelium of coronary arteries to induce thrombosis. Occlusive thrombi
      developed in all dogs in the saline group (38 +/- 4 minutes) and the L-NNA group
      (30 +/- 6 minutes), in 6 of 7 dogs in the L-arginine group (81 +/- 18 minutes),
      and in 6 of 11 dogs in the SNP group (102 +/- 21 minutes) (P < .01). The time to
      thrombus was prolonged by L-arginine (P < .05) and SNP (P < .01). After 3 hours
      of thrombus formation in coronary arteries, tissue plasminogen activator and
      heparin were administered intravenously. Thrombi were lysed in 4 (of 8) dogs in
      the saline group (71 +/- 8 minutes), in 4 (of 8) dogs in the L-NNA group (72 +/-
      8 minutes), in 4 (of 6) dogs in the L-arginine group (50 +/- 14 minutes), and in
      4 (of 6) dogs in the SNP group (49 +/- 11 minutes) (P > .05). After thrombolysis,
      coronary artery reocclusion developed in all reperfused dogs in the saline group
      (30 +/- 8 minutes) and in the L-NNA group (48 +/- 12 minutes), in 3 (of 4)
      reperfused dogs in the L-arginine group (123 +/- 26 minutes), and in 3 (of 4)
      reperfused dogs in the SNP group (128 +/- 19 minutes) (P < .01). The ex vivo
      platelet aggregation induced by collagen was inhibited after in vivo treatment
      with L-arginine or SNP. CONCLUSIONS: Increasing NO production or giving an NO
      donor may inhibit platelet aggregation and delay intracoronary thrombus formation
      and reocclusion after thrombolysis.

PMID- 7641336
TI  - Bioenergetic consequences of left ventricular remodeling.
AB  - BACKGROUND: Left ventricular (LV) remodeling is associated with LV dysfunction
      and decrease of coronary flow reserve. The underlying mechanisms responsible for
      these alterations are unclear. Changes in myocardial high-energy phosphate levels
      may be associated with these alterations. METHODS AND RESULTS: Twelve dogs with
      LV remodeling secondary to discrete necrosis produced by transmyocardial DC shock
      were compared with 8 normal dogs. LV mass and end-diastolic volume were measured
      by magnetic resonance imaging 7 days before and 12.9 +/- 1.3 months after DC
      shock. Transmurally localized 31P nuclear magnetic resonance spectra from five
      layers across the LV wall were obtained simultaneously with transmural blood flow
      measurements (microspheres) under basal conditions and during pacing at 200 and
      240 beats per minute. LV mass and end-diastolic volume were significantly
      increased after DC shock (33% and 26%, respectively, each P < .01). Under basal
      conditions, the subendocardial creatine phosphate (CP)/ATP ratio was
      significantly lower in remodeled LV compared with the control group (1.71 +/-
      0.09 versus 2.04 +/- 0.09, P < .05). The subendocardial CP/ATP ratio was
      inversely correlated with both the increase in LV mass and LV end-diastolic
      volume (r = -.77 and r = -.70, P < .01 and P < .05, respectively). In remodeled
      myocardium, pacing induced a significant increase in LV end-diastolic pressure
      (from 8 +/- 1 to 20 +/- 3 mm Hg, P < .05), which was accompanied by a significant
      decrease of subendocardial/subepicardial (Endo/Epi) blood flow ratio (from 1.01
      +/- 0.10 to 0.63 +/- 0.11, P < .05) and a significant decrease in subendocardial
      CP/ATP ratio (from 1.78 +/- 0.07 to 1.61 +/- 0.10, P < .05) and increase of delta
      P(i)/ATP ratio (from 0 to 0.24 +/- 0.05, P < .01). The decrease in subendocardial
      CP/ATP ratio was correlated with the decrease in Endo/Epi blood flow ratio (r =
      .79, P < .05). CONCLUSIONS: These results demonstrate that alterations in
      myocardial high-energy phosphate levels are correlated with the extent of LV
      remodeling. In remodeled hearts, pacing-induced tachycardia produces further
      changes of myocardial high-energy phosphate levels in the subendocardium that
      appear to be related to ventricular dysfunction and redistribution of blood flow
      away from the subendocardium.

PMID- 7641337
TI  - Angiotensin II augments reflex activity of the sympathetic nervous system during
      cardiopulmonary resuscitation in pigs.
AB  - BACKGROUND: During hypotensive states, angiotensin II augments reflex activity of
      the sympathetic nervous system. The purpose of the present study was to assess
      the effects of this vasoconstrictor on myocardial blood flow and plasma
      catecholamine concentrations during and after CPR. METHODS AND RESULTS: After 4
      minutes of ventricular fibrillation and 3 minutes of open-chest CPR, 14 pigs (24
      to 26 kg) were randomized into two groups receiving either saline (n = 7) or 0.05
      mg/kg angiotensin II (n = 7). Arterial plasma catecholamine concentration was
      measured with high-pressure liquid chromatography. Organ blood flow was measured
      with radiolabeled microspheres. During CPR, after drug administration, left
      ventricular myocardial blood flow was significantly higher in the angiotensin II
      treated group than in the control group. During CPR, median epinephrine
      concentrations before and 90 seconds and 5 minutes after drug administration were
      63.0, 35.2, and 22.5 ng/mL, respectively, in the control group and 63.2, 139.8,
      and 154.2 ng/mL, respectively, in the angiotensin II group (P < .001 at 90
      seconds and P < .01 at 5 minutes). At the same times, median norepinephrine
      concentrations were 52.6, 59.8, and 33.9 ng/mL, respectively, in the control
      group and 42.5, 98.7, and 111.3 ng/mL, respectively, in the angiotensin II group
      (P < .01 at 5 minutes). Restoration of spontaneous circulation was possible in
      all of the angiotensin II-treated pigs, whereas only 3 of the 7 saline-treated
      pigs could be resuscitated. At 5 minutes after successful resuscitation,
      epinephrine was 6.8 ng/mL in the control group and 16.1 ng/mL in the angiotensin
      II group (P < .05). CONCLUSIONS: During CPR, angiotensin II appears to increase
      coronary perfusion pressure and myocardial blood flow, not only by direct
      peripheral arteriolar vasoconstriction via angiotensin II receptors but also by
      inducing a massive catecholamine release with adrenergic peripheral
      vasoconstriction.

PMID- 7641338
TI  - Automated echocardiographic measures of right ventricular area as an index of
      volume and end-systolic pressure-area relations to assess right ventricular
      function.
AB  - BACKGROUND: On-line determination of right ventricular (RV) volume to assess its
      function is clinically difficult. Echocardiographic automated border detection
      measures of left ventricular (LV) cavity area have been shown to reflect changes
      in volume, and pressure-area relations have been used to estimate LV
      contractility. The potential for RV cavity area to estimate changes in volume and
      to assess RV function, however, has not been evaluated. Accordingly, the
      objective of this study was to determine the relation between echocardiographic
      automated border-detected RV cross-sectional area and true volume and to assess
      the potential for end-systolic pressure-area relations to estimate RV function in
      an isovolumically contracting isolated canine heart preparation. METHODS AND
      RESULTS: Eight excised dog hearts with both right and left intraventricular
      balloons were perfused in an ex vivo apparatus in which both ventricular volumes
      were controlled independently. RV area data from the level of the left
      midventricular short-axis plane and pressure data were recorded on a computer
      through a customized hardware and software interface with the ultrasound system.
      RV volumes were varied from 9.4 +/- 3.9 to 43.8 +/- 6.9 mL at each of three
      different LV volume ranges (low range, 12.5 +/- 3.8 mL; medium range, 23.9 +/-
      5.6 mL; and high range, 37.5 +/- 5.4 mL). The variation of RV area during
      isovolumic contraction, which we called deformational area change, was
      considerable (1.49 +/- 0.68 cm2 mean +/- SD) but did not change significantly
      with changing RV and LV volumes. Linear regression analysis correlated the
      maximum, minimum, and mean automated border-detected RV area during isovolumic
      contraction with absolute volume. A predominantly linear relation was observed,
      with the group mean r = .98 (y = 0.16x + 0.97; SEE = 0.21 cm2). The effect of LV
      volume on RV area-volume relation was a significant parallel downward shift (P <
      .05) by increases in LV volume. End-systolic pressure-area and pressure-volume
      relations using simultaneously RV pressure were both highly linear and covaried
      with changing LV volume. CONCLUSIONS: Echocardiographic automated border-detected
      RV area reflects changes in RV volume under a constant LV volume, and the derived
      end-systolic pressure-area relation has potential for on-line assessment of RV
      function.

PMID- 7641339
TI  - Blood pressure measurement in childhood epidemiological studies.
AB  - BACKGROUND: Accurate measurement of blood pressure in childhood epidemiological
      studies requires standardized conditions, valid instruments, and multiple
      measurements. METHODS AND RESULTS: We used published literature and our own data
      to make recommendations on the reduction of biases caused by various technical
      factors, to discuss the advantages and disadvantages of selected measurement
      devices, and to evaluate the optimal number of visits and measurements per visit
      for accurate estimation of a child's blood pressure level. The conditions under
      which blood pressure is measured should be standardized. This includes training
      and certification to minimize observer biases; equipment factors such as use of
      an appropriate cuff bladder size, subject factors such as minimizing activities
      before and during the reading, environmental factors such as accounting for the
      time of day and ambient temperature, and technique factors such as recording both
      the fourth and fifth Korotkoff sounds. The choice of instrument for measuring
      blood pressure depends on the goals of the study and the resources available to
      the investigators. CONCLUSIONS: Although relatively economical and easy to use,
      the standard mercury sphygmomanometer is subject to the bias resulting from
      knowledge of earlier readings. The random-zero sphygmomanometer overcomes this
      bias, but it is more expensive and difficult to use and may underestimate blood
      pressure levels. In contrast to auscultatory devices, automated oscillometric
      devices are not subject to observer biases. They are gaining wider use and may be
      especially appropriate for younger children. However, they are expensive, and
      each model requires validation before use in epidemiological studies. Ambulatory
      blood pressure monitoring represents a potentially useful technique for future
      epidemiological studies. Multiple measurements are vital in estimating a child's
      blood pressure, and the number of visits, days or weeks apart, is at least as
      important as the number of measurements per visit.

PMID- 7641340
TI  - Images in Cardiovascular medicine. Noninvasive diagnosis of cor triatriatum.

PMID- 7641341
TI  - Benefit of respiratory muscle training on exercise capacity.

PMID- 7641342
TI  - Prodromal angina limits infarct size: a role for ischemic preconditioning.

PMID- 7641343
TI  - Dual chamber pacemaker therapy in obstructive hypertrophic cardiomyopathy.

PMID- 7641344
TI  - Is the benefit of preinfarction angina on infarct size due to faster coronary
      recanalization?

PMID- 7641345
TI  - Lipid lowering and enhancement of fibrinolysis with niacin.

PMID- 7641346
TI  - Prevalence of hypertrophic cardiomyopathy and limitations of screening methods.

PMID- 7641347
TI  - Osteopontin expression is increased in the heritable cardiomyopathy of Syrian
      hamsters.
AB  - BACKGROUND: Osteopontin, a noncollagenous matrix protein, is transiently
      expressed in the heart after experimental cardiac injury, but its expression in
      states of continuing cardiac remodeling is unknown. We evaluated osteopontin
      expression in the heritable cardiomyopathy of the Syrian hamster. METHODS AND
      RESULTS: Hamster hearts were obtained for RNA isolation and analysis and in situ
      hybridization from two groups: normal control animals (n = 4) and untreated
      cardiomyopathic hamsters (n = 5). Osteopontin mRNA was 12-fold greater in
      cardiomyopathic hearts compared with normal controls (1.76 +/- 0.31 versus 0.14
      +/- 0.04 arbitrary units normalized to GAPDH, mean +/- SEM, P < .05). In situ
      hybridization was used to define the origin of osteopontin in the heart.
      Osteopontin mRNA above background levels was not detected in sections from
      noncardiomyopathic hamster hearts but was readily detected in sections from
      cardiomyopathic hamsters, in which it originated in cells morphologically
      consistent with tissue macrophages. CONCLUSIONS: In the hamster, osteopontin is
      expressed in heritably cardiomyopathic hearts under conditions of chronic injury
      and repair, and the source of ostopontin message appears to be issue macrophage
      like cells in foci of inflammation. This model could be used to evaluate the
      biological role of osteopontin in myocardial inflammation and remodeling.

PMID- 7641348
TI  - Relation between ischemia time, infarct size, and left ventricular function in
      humans.
AB  - BACKGROUND: Experimental studies indicate that duration of ischemia is a major
      determinant of myocardial infarct size, but only limited information is available
      about the relation between ischemia time and infarct size in individual patients.
      This prospective study sought to document the role of ischemia time as a
      determinant of infarct size in humans. METHODS AND RESULTS: We studied 61
      patients (50 men, 11 women) 57 +/- 11 years old admitted with a first infarct (31
      anterior, 30 inferior) who underwent continuous 12-lead ECG monitoring to
      document ischemia time. Infarct size (32-point QRS score on day 7) and changes in
      regional myocardial wall motion (echocardiography) during the following month
      were related to ischemia time. Among patients with < 3 hours of ischemia (n =
      16), mean infarct size on day 7 was 21 +/- 13% of potential infarct size; in
      patients with 3 to 6 hours of ischemia (n = 23), infarct size was 38 +/- 18% of
      potential (P < .05 versus 0 to 3 hours of ischemia); and in patients with 6 to 9
      hours of ischemia (n = 10), infarct size was 66 +/- 14% of potential (P < .05
      versus 3 to 6 hours). In contrast, the 12 patients with an ischemia time > 9
      hours had a final infarct size of 77 +/- 10% of potential (P < .01 versus 3 to 6
      hours). Multivariate regression identified size of risk region, duration of
      ischemia, and degree of initial ST-segment elevation as independent predictors of
      infarct size, of which the most important variable was ischemia time. The
      regression models accurately predicted both individual absolute infarct size (R2
      = .83) and individual infarct/risk ratio (R2 = .74). Patients with < 6 hours of
      ischemia exhibited significant recovery of myocardial wall motion by day 7 (wall
      motion score, 2.1 +/- 1.4 versus 5.7 +/- 3.2 on day 1, P < .01). Patients with 6
      to 9 hours of ischemia had some recovery by 1 month (score, 6.3 +/- 4.4 versus
      10.9 +/- 3.8 on day 1, P < .01), but patients with > 9 hours of ischemia had
      little recovery of wall motion by 1 month (score, 10.3 +/- 4.5 versus 12.8 +/-
      3.1 on day 1, P < .05). CONCLUSIONS: Measurement of ischemia time allows improved
      prediction of infarct size in humans. Significant myocardial salvage and
      functional recovery may be achieved by reperfusion up to 9 hours after coronary
      occlusion. Continuous ST-segment monitoring should be used to measure ischemia
      time and guide interventions to reperfuse the infarct artery.

PMID- 7641349
TI  - Subclinical disease as an independent risk factor for cardiovascular disease.
AB  - BACKGROUND: The primary aim of the present study was to determine the relation
      between measures of subclinical cardiovascular disease and the incidence of
      clinical cardiovascular disease among 5201 adults 65 years of age or older who
      were participating in the Cardiovascular Health Study. METHODS AND RESULTS: A new
      method of classifying subclinical disease at baseline examination in the
      Cardiovascular Health Study included measures of ankle-brachial blood pressure,
      carotid artery stenosis and wall thickness, ECG and echocardiographic
      abnormalities, and positive response to the Rose Angina and Claudication
      Questionnaire. Participants were followed for an average of 2.39 years (maximum,
      3 years). For participants without evidence of clinical cardiovascular disease at
      baseline, the presence of subclinical disease compared with no subclinical
      disease was associated with a significant increased risk of incident total
      coronary heart disease including CHD deaths and nonfatal MI and angina pectoris
      for both men and women. For individuals with subclinical disease, the increased
      risk of total coronary heart disease was 2.0 for men and 2.5 for women, and the
      increased risk of total mortality was 2.9 for men and 1.7 for women. The
      increased risk changed little after adjustment for other risk factors, including
      lipoprotein levels, blood pressure, smoking, and diabetes. CONCLUSIONS: The
      measurement of subclinical disease provides an approach for identifying high-risk
      older individuals who may be candidates for more active intervention to prevent
      clinical disease.

PMID- 7641350
TI  - Hirulog in the treatment of unstable angina. Results of the Thrombin Inhibition
      in Myocardial Ischemia (TIMI) 7 trial.
AB  - BACKGROUND: Direct thrombin inhibitors are a new class of drugs that may offer a
      more effective and potentially simpler alternative to heparin. Hirulog is a
      synthetic peptide based on the leech-derived compound hirudin and, like hirudin,
      is a highly specific, direct inhibitor of free and clot-bound thrombin. METHODS
      AND RESULTS: TIMI 7 was a randomized, double-blind study of Hirulog, given with
      325 mg/d aspirin to 410 patients with unstable angina. Patients received a
      constant infusion of Hirulog for 72 hours at one of four doses: 0.02 (n = 160),
      0.25 (n = 81), 0.5 (n = 88), and 1.0 (n = 81) mg.kg-1.h-1. The primary efficacy
      end point was "unsatisfactory outcome," defined as death, nonfatal myocardial
      infarction (MI), rapid clinical deterioration, or recurrent ischemic pain at rest
      with ECG changes by 72 hours. Unsatisfactory outcome was not different among the
      four dose groups: 8.1%, 6.2%, 11.4%, and 6.2% (P = NS). However, the secondary
      end point of death or nonfatal MI through hospital discharge occurred in 10.0% of
      patients treated with 0.02 mg.kg-1.h-1 compared with 3.2% of patients treated
      with the three higher doses of Hirulog (0.25, 0.5, and 1.0 mg.kg-1.h-1, P =
      .008). Only 2 of 410 patients (0.5%) experienced a major hemorrhage attributed to
      Hirulog. CONCLUSIONS: The direct thrombin inhibitor Hirulog is a promising new
      antithrombotic agent that deserves further study. The results of TIMI 7 lend
      support to the use of an antithrombin agent with aspirin in patients with
      unstable angina.

PMID- 7641351
TI  - Predictors and sequelae of distal embolization during saphenous vein graft
      intervention from the CAVEAT-II trial. Coronary Angioplasty Versus Excisional
      Atherectomy Trial.
AB  - BACKGROUND: The purpose of this study was to identify the predictors and sequelae
      of distal embolization from a multicenter, randomized trial of saphenous vein
      graft intervention. The CAVEAT-II trial demonstrated that saphenous vein graft
      directional coronary atherectomy (DCA) was associated with greater angiographic
      success and less need for repeat intervention compared with percutaneous
      transluminal coronary angioplasty (PTCA) but at the cost of more acute
      complications--notably distal embolization. METHODS AND RESULTS: In CAVEAT-II,
      305 patients were randomly assigned to DCA (149 patients) or PTCA (156 patients)
      for lesions with > 60% diameter stenosis in vein grafts > or = 3 mm in diameter.
      Distal embolization occurred in 20 patients (13.4%) assigned to DCA and 8
      patients (5.1%) assigned to PTCA (P = .011). Independent predictors of distal
      embolization were use of DCA (71% in distal embolization patients versus 47% in
      patients without distal embolization, P = .011) and presence of thrombus (39% in
      distal embolization patients versus 14% in patients without distal embolization,
      P < .00). In-hospital adverse events were more frequent after distal
      embolization; 71% versus 20%, odds ratio plus (95% confidence intervals) 9.87
      (4.65, 20.94). At 12-month follow-up, adverse event rates were also higher in
      patients with distal embolization (odds ratio, 3.05 [1.95, 4.76]). CONCLUSIONS:
      In this first prospective multicenter trial of saphenous vein graft intervention,
      distal embolization was more common after DCA than PTCA and in lesions containing
      thrombus. It also was associated with worse in-hospital and 12-month outcomes.
      The risk and sequelae of distal embolization should be considered when choosing a
      treatment strategy for vein graft disease.

PMID- 7641352
TI  - In-hospital cost of percutaneous coronary revascularization. Critical
      determinants and implications.
AB  - BACKGROUND: Hospital charges associated with percutaneous transluminal coronary
      revascularization (PTCR) in the United States exceeded $6 billion in 1994 and are
      likely to be constrained in some manner in the near future. Despite this high
      cost to the public, little is known about the major determinants and sources of
      variability of PTCR. METHODS AND RESULTS: From a consecutive series of 1258
      procedures with attempted PTCR at a single tertiary referral center, we analyzed
      65 clinical, angiographic, physician, and outcome variables as potential
      correlates of total (hospital and physician) cost. Direct and indirect costs,
      both hospital and physician, were determined on the basis of resource utilization
      using "top-down" methodology and were available for 1237 procedures (1086
      patients) (98.3%). Mean (+/- SD) patient age was 62 +/- 11 years, 76% were male,
      3% had acute myocardial infarction, 71% had unstable angina, 58% had multivessel
      disease, left ventricular ejection fraction was 54 +/- 12%, 26% had use of at
      least one nonballoon revascularization device, and median length of stay was 4.4
      days. Procedural success was obtained in 89%, and major complications (death,
      bypass surgery, or Q-wave myocardial infarction) occurred in 3.8%. The median
      cost was $9176, but it was asymmetrically distributed, and the interquartile and
      total ranges were wide ($7333 to $13,845 and $3422 to $193,474, respectively).
      Analyses of independent correlates of cost and loge(cost) were performed using
      multivariate linear regression in training and test populations. Modeling found
      15 independent preprocedural correlates of loge(cost) (R2 = .37) and 23 overall
      correlates (R2 = .65), excluding length of stay per se. Additional of length of
      stay to the model increased the explanatory power of the model to R2 = .82.
      Preprocedural variables most predictive of loge(cost) included presentation with
      acute myocardial infarction, decision delay (> 48 hours between admission and
      diagnostic angiography and/or > 24 hours between angiography and intervention),
      weekend delay, use of intra-aortic balloon counterpulsation, intention to stent,
      creatinine > or = 2.0 mg%, and lesion complexity (modified American College of
      Cardiology/American Heart Association score) (all P < .001). In the model that
      included postprocedural variables as well, length of stay, noncardiac death,
      urgent bypass surgery, use of the Rotablator, Q-wave myocardial infarction, rise
      in creatinine > or = 1.0%, and blood product transfusion were all strong
      independent correlates of loge(cost) (P < .001). CONCLUSIONS: The range of total
      hospital costs associated with percutaneous intervention is extraordinarily wide.
      Baseline patient characteristics account for nearly half of the explained
      variance, but procedural complications and system delays account for much of the
      remainder. Quantification of the determinants of cost may promote more
      economically efficient care in the future.

PMID- 7641353
TI  - Incremental doses of dobutamine induce a biphasic response in dysfunctional left
      ventricular regions subtending coronary stenoses.
AB  - BACKGROUND: Dobutamine stress echocardiography has been proposed as a diagnostic
      tool to identify viable myocardium. How regional wall thickening responds to
      dobutamine in the ischemic or short-term hibernating myocardium has not been
      adequately defined. We hypothesized that regional wall thickening would improve
      initially and subsequently deteriorate with incremental doses of dobutamine in
      viable myocardial regions supplied by a stenotic coronary artery. This study was
      undertaken to determine whether this biphasic pattern of regional function
      characterizes the response of ischemic or hibernating myocardium to dobutamine
      and to explore the factors and mechanisms that determine this response. METHODS
      AND RESULTS: Twenty-six pigs in four groups were studied: a control group (n = 5)
      to assess the response of myocardium perfused by nonstenotic coronary artery to
      incremental doses of dobutamine, and three experimental groups with a left
      anterior descending coronary artery stenosis producing acute myocardial ischemia
      (n = 7), short-term myocardial hibernation for 90 minutes (n = 7), and short-term
      hibernation for 24 hours (n = 7) to determine the functional and metabolic
      response to dobutamine under these conditions. Regional coronary flow was reduced
      to 40% to 60% of baseline, with significant reductions of regional wall
      thickening as measured by two-dimensional echocardiography and sonomicrometers.
      An incremental dobutamine infusion from 2.5 to 25 micrograms.kg-1.min-1 increased
      wall thickening and coronary flow without lactate production in the control
      group. In the other three groups, during the incremental dobutamine infusion,
      regional wall thickening improved initially, from 11.4 +/- 7.5% to 19.8 +/-
      11.4%, P < .01, at dobutamine doses of 2.5 to 10 (4.5 +/- 2.2) micrograms.min
      1.kg-1 but deteriorated subsequently to 5.0 +/- 5.8% at the maximal dose of
      dobutamine of 12.6 +/- 4.1 micrograms.min-1.kg-1. The initial improvement of
      regional wall thickening was associated with a small increase in regional
      coronary flow (from 0.53 +/- 0.18 to 0.68 +/- 0.25 mL.min-1.g-1 myocardium, P <
      .05) and with regional lactate production. High doses of dobutamine did not
      further increase regional coronary flow but markedly increased lactate production
      and induced regional myocardial acidosis (pH 7.26 +/- 0.07). The biphasic pattern
      of response to dobutamine was observed in each of the three experimental groups.
      Both peak improvement and peak deterioration occurred earlier and at lower
      dobutamine dose levels in the group with acute ischemia compared with the group
      with short-term hibernation for 24 hours (P < .05). CONCLUSIONS: A biphasic
      response of wall thickening to incremental dobutamine with initial improvement
      and subsequent deterioration is characteristic of ischemic or short-term
      hibernating myocardium. The initial low-dose dobutamine infusion improved wall
      thickening in the ischemic or hibernating myocardial region to a modest level.
      This initial modest improvement was transient and at the expense of metabolic
      deterioration of myocardial ischemia, so that at higher doses during prolonged
      dobutamine infusion, wall thickening deteriorated, lactate accumulated, and
      myocardial acidosis developed.

PMID- 7641354
TI  - Attenuation of the synthesis of plasminogen activator inhibitor type 1 by niacin.
      A potential link between lipid lowering and fibrinolysis.
AB  - BACKGROUND: Plasminogen activator inhibitor type 1 (PAI-1), the primary
      physiological inhibitor of endogenous plasminogen activators, has been implicated
      as a potentiating factor in atherogenesis as well as in coronary thrombosis. We
      and others have observed attenuation of PAI-1 expression by gemfibrozil both in
      vivo and in vitro. METHODS AND RESULTS: To determine whether other lipid-lowering
      agents with different mechanisms of action exert similar effects, we exposed Hep
      G2 cells, a highly differentiated human hepatoma cell line, to selected
      concentrations of niacin. Accumulation of PAI-1 protein, assayed with an ELISA,
      decreased in conditioned media by 72% in 48 hours in a specific, concentration
      dependent fashion. Metabolic labeling experiments demonstrated a decrease in the
      rate of PAI-1 synthesis. Northern blot analysis demonstrated a preceding,
      parallel, and specific decrease in the concentration of PAI-1 mRNA. Niacin
      attenuated the increased PAI-1 synthesis induced by mediators released from
      thrombi as well. Thus, with 4.25 ng/mL transforming growth factor-beta 1, PAI-1
      accumulation increased 4.5-fold in conditioned media in 48 hours. However, niacin
      attenuated the increase by 65%. Again, both the rate of PAI-1 synthesis and PAI-1
      mRNA were reduced. The increased plasma PAI-1 activity and PAI-1 mRNA in liver
      induced by dexamethasone (0.8 mg IP) in vivo in rats were attenuated by 3 weeks
      of pretreatment with niacin. CONCLUSIONS: These results suggest that niacin, by
      decreasing PAI-1 expression, may potentiate fibrinolysis, thereby decreasing the
      stimulation of atherogenesis by clot-associated mitogens associated with
      microthrombi. Furthermore, the results imply that a pathogenetic link may exist
      between intracellular lipid metabolism and regulation of expression of
      fibrinolytic system components.

PMID- 7641355
TI  - Long-term (5-year) changes in HDL cholesterol in cardiac rehabilitation patients.
      Do sex differences exist?
AB  - BACKGROUND: It is unknown whether the benefits of a cardiac rehabilitation
      program on HDL cholesterol (HDL-C) are equally achieved in men and women. To
      study this, we compared changes in HDL-C and other lipids in a large group of men
      and women participating in a cardiac rehabilitation program for up to 5 years.
      METHODS AND RESULTS: We compared changes in HDL-C and other fasting lipids in 553
      men and 166 women participating in a cardiac rehabilitation program at baseline
      and then annually for up to 5 years. Patients exercised 3 days a week at 70% to
      85% of their maximum heart rate predetermined by a symptom-limited treadmill
      test. Aerobic capacity was estimated in metabolic equivalents (METs), and percent
      body fat was determined by skin-fold measurements. Baseline HDL-C, LDL
      cholesterol (LDL-C), and total cholesterol were significantly higher in women,
      whereas the ratio of total cholesterol to HDL-C was lower. Although both men and
      women showed an increase in HDL-C after 1 year (10% and 7%, respectively), only
      the women's level continued to increase over 5 years (20% versus 5% for men, P =
      .03). The sex difference in change in HDL-C remained after adjustment for age and
      smoking. A nonsignificant trend toward a greater change in HDL-C in women existed
      after adjustment for baseline percent body fat and estimated METs. The change in
      the ratio of total cholesterol to HDL-C was also more favorable in women, with a
      38% decrease over 5 years compared with a 14% decrease in men (P = .01). Total
      cholesterol decreased by 20% in women and 8% in men (P = .001), whereas LDL-C
      dropped by 34% in women and 15% in men (P = .0001). There was no sex difference
      in change in triglycerides. CONCLUSIONS: Women with heart disease who participate
      in a cardiac rehabilitation program may achieve greater lipid benefits over
      longer periods of time than previously demonstrated in men.

PMID- 7641356
TI  - Alterations of sarcoplasmic reticulum proteins in failing human dilated
      cardiomyopathy.
AB  - BACKGROUND: Previous studies provide considerable evidence that excitation
      contraction coupling may be disturbed at the level of the sarcoplasmic reticulum
      (SR) in the failing human heart. Disturbed SR function may result from altered
      expression of calcium-handling proteins. METHODS AND RESULTS: Levels of SR
      proteins involved in calcium release (ryanodine receptor), calcium binding
      (calsequestrin, calreticulin), and calcium uptake (calcium ATPase, phospholamban)
      were measured by Western blot analysis in nonfailing human myocardium (n = 7) and
      in end-stage failing myocardium due to dilated cardiomyopathy (n = 14). The
      levels of the ryanodine receptor, calsequestrin, and calreticulin were not
      significantly different in nonfailing and failing human myocardium. Phospholamban
      protein levels (pentameric form) normalized per total protein were decreased by
      18% in the failing myocardium (P < .05). However, phospholamban protein levels
      were not significantly different in failing and nonfailing myocardium when
      normalization was performed per calsequestrin. Protein levels of SR calcium
      ATPase, normalized per total protein or per calsequestrin, were decreased by 41%
      (P < .001) or 33% (P < .05), respectively, in the failing myocardium.
      Furthermore, SR calcium ATPase was decreased relative to ryanodine receptor by
      37% (P < .05) and relative to phospholamban by 28% (P < .05). CONCLUSIONS: Levels
      of SR proteins involved in calcium binding and release are unchanged in failing
      dilated cardiomyopathy. In contrast, protein levels of calcium ATPase involved in
      SR calcium uptake are reduced in the failing myocardium. Moreover, SR calcium
      ATPase is decreased relative to its inhibitory protein, phospholamban.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7641357
TI  - Prevalence of hypertrophic cardiomyopathy in a general population of young
      adults. Echocardiographic analysis of 4111 subjects in the CARDIA Study. Coronary
      Artery Risk Development in (Young) Adults.
AB  - BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a genetically transmitted
      disease and an important cause of morbidity and sudden cardiac death in young
      people, including competitive athletes. At present, however, few data exist to
      estimate the prevalence of this disease in large populations. METHODS AND
      RESULTS: As part of the Coronary Artery Risk Development in (Young) Adults
      (CARDIA) Study, an epidemiological study of coronary risk factors, 4111 men and
      women 23 to 35 years of age selected from the general population of four urban
      centers had technically satisfactory echocardiographic studies during 1987
      through 1988. Probable or definite echocardiographic evidence of HCM was present
      in 7 subjects (0.17%) on the basis of identification of a hypertrophied,
      nondilated left ventricle and maximal wall thickness > or = 15 mm that were not
      associated with systemic hypertension. Prevalence in men and women was
      0.26:0.09%; in blacks and whites, 0.24:0.10%. Ventricular septal thickness was 15
      to 21 mm (mean, 17 mm) in the 7 subjects. Only 1 of the 7 subjects had ever
      experienced important cardiac symptoms attributable to HCM, had previously been
      suspected of having cardiovascular disease, or had obstruction to left
      ventricular outflow; 4 other subjects had relatively mild systolic anterior
      motion of the mitral valve that was insufficient to produce dynamic basal outflow
      obstruction. ECGs were abnormal in 5 of the 7 subjects. Five other study subjects
      had left ventricular wall thicknesses of 15 to 21 mm that were a consequence of
      systemic hypertension. CONCLUSIONS: HCM was present in about 2 of 1000 young
      adults. These unique population-based data will aid in assessments of the impact
      of HCM-related mortality and morbidity in the general population and the
      practicality of screening large populations for HCM, including those comprising
      competitive athletes.

PMID- 7641358
TI  - Carcinoid heart disease. Correlation of high serotonin levels with valvular
      abnormalities detected by cardiac catheterization and echocardiography.
AB  - BACKGROUND: Although serotonin has been postulated as an etiologic agent in the
      development of carcinoid heart disease, no direct evidence for different ambient
      serotonin levels in cardiac and noncardiac patients has been reported to date.
      METHODS AND RESULTS: The present study reviews our experience with 604 patients
      in the Duke Carcinoid Database. Nineteen patients with proven carcinoid heart
      disease (by cardiac catheterization and/or echocardiogram) were compared with the
      remaining 585 noncardiac patients in the database with regard to circulating
      serotonin and its principal metabolite, 5-hydroxyindole acetic acid (5-HIAA). No
      significant demographic differences existed between the cardiac and noncardiac
      groups; however, typical carcinoid syndrome symptoms (ie, flushing and diarrhea)
      were almost threefold more common in the cardiac group (P < .001). Compared with
      the noncardiac group, heart disease patients demonstrated strikingly higher (P <
      .0001) mean serum serotonin (9750 versus 4350 pmol/mL), plasma serotonin (1130
      versus 426 pmol/mL), platelet serotonin (6240 versus 2700 pmol/mg protein), and
      urine 5-HIAA (219 versus 55.3 mg/24 h) levels. The spectrum of heart disease
      among the 19 patients showed a strong right-sided valvular predominance, with
      tricuspid regurgitation being the most common valvular dysfunction (92% by
      cardiac catheterization; 100% by echocardiogram). CONCLUSIONS: These data suggest
      that serotonin plays a major role in the pathogenesis of the cardiac plaque
      formation observed in carcinoid patients.

PMID- 7641359
TI  - Myocardial blood flow response to pacing tachycardia and to dipyridamole infusion
      in patients with dilated cardiomyopathy without overt heart failure. A
      quantitative assessment by positron emission tomography.
AB  - BACKGROUND: Myocardial blood flow (MBF) impairment has been documented in
      advanced dilated cardiomyopathy (DCM) in which hemodynamic factors, secondary to
      severe ventricular dysfunction, may limit myocardial perfusion. To assess whether
      MBF impairment in DCM may also be present independent of hemodynamic factors, the
      present study was designed to quantify myocardial perfusion in patients with mild
      disease without overt heart failure. METHODS AND RESULTS: Absolute regional MBF
      (milliliters per minute per gram) was measured by positron emission tomography
      and 13N-ammonia in resting conditions, during pacing-induced tachycardia, and
      after dipyridamole infusion (0.56 mg/kg over 4 minutes) in 22 DCM patients and in
      13 healthy subjects. Patients were in New York Heart Association functional class
      I-II and showed depressed left ventricular (LV) ejection fraction by radionuclide
      angiography (35 +/- 8%; range, 21% to 48%), normal coronary angiography, and
      normal or moderately increased LV end-diastolic pressure (9.2 +/- 5.5 mm Hg;
      range, 2 to 20 mm Hg). There were no differences in arterial blood pressure,
      heart rate, and rate-pressure product between patients and control subjects in
      the three study conditions. Compared with control subjects, DCM patients had
      lower mean MBF at rest (0.80 +/- 0.25 versus 1.08 +/- 0.20 mL.min-1.g-1, P <
      .01), during atrial pacing tachycardia (1.21 +/- 0.59 versus 2.03 +/- 0.64 mL.min
      1.g-1, P < .01), and after dipyridamole infusion (1.91 +/- 0.76 versus 3.78 +/-
      0.86 mL.min-1.g-1, P < .01). LV MBF values were related to baseline LV end
      diastolic pressure at rest (r = -.57, P < .01) and during pacing (r = -.67, P <
      .01) but not after dipyridamole infusion (r = .19, P = .40). Five patients had LV
      end-diastolic pressure > 12 mm Hg; in 4, myocardial perfusion was severely
      depressed both at baseline and in response to stress. CONCLUSIONS: In patients
      with DCM without overt heart failure, myocardial perfusion is impaired both at
      rest and in response to vasodilating stimuli. The abnormalities in vasodilating
      capability can be present despite normal hemodynamics; progression of the disease
      is associated with more depressed myocardial perfusion.

PMID- 7641360
TI  - Left ventricular hypertrophy has a greater impact on survival in women than in
      men.
AB  - BACKGROUND: Echocardiographically determined left ventricular hypertrophy (LVH)
      has a well-demonstrated association with cardiovascular morbidity and mortality.
      However, whether or not there is a sex differential in the impact of LVH on
      mortality has never been systematically explored. METHODS AND RESULTS: This study
      enrolled 436 consecutive black patients (163 men and 273 women) free of
      angiographic coronary artery disease from a hospital registry. LVH (left
      ventricular [LV] mass/body surface area > or = 117 g/m2 in men and > or = 104
      g/m2 in women) was present in 84 men (52%) and 119 women (44%). During a mean of
      5 years' follow-up (range, 0 to 9), 49 patients (26 men and 23 women) died. The
      mortality rate was 5.40 per 100 patient-years in men with LVH and 2.58 in men
      without LVH (crude relative risk [RR] = 2.09) and 3.21 and 0.66, respectively, in
      women (RR = 4.87). In Cox regression analysis, adjusting for age, hypertension,
      and ejection fraction, the RR of total death for LVH versus non-LVH was 2.0 (95%
      confidence interval [CI], 0.8 to 5.0) in men and 14.3 (95% CI, 1.6 to 11.7) in
      women. For cardiac death, RR was 1.3 (95% CI, 0.4 to 3.7) and 7.5 (95% CI, 1.6 to
      33.8) in men and women, respectively. Analyses using LV mass indexed by height or
      height with the use of different LVH cut points, comparing patients in the
      highest sex-specific tertile of mass index to those in the lower two tertiles,
      and the use of LV mass indexes as continuous variables similarly demonstrated a
      greater increase in risk of either fatal end point among women than men.
      CONCLUSIONS: These findings indicate a sex difference in the contribution of LV
      mass and hypertrophy to mortality in the absence of coronary artery disease.

PMID- 7641361
TI  - Effects of valve surgery on left ventricular contractile function in patients
      with long-term mitral regurgitation.
AB  - BACKGROUND: Patients with long-term mitral regurgitation were studied both before
      and 1 year after successful valve surgery to test the hypothesis that impaired
      left ventricular contractile function improves after surgery for long-term mitral
      regurgitation in humans. METHODS AND RESULTS: Fifteen patients with long-term
      mitral regurgitation were studied. Micromanometer left ventricular pressures and
      radionuclide angiograms for left ventricular volumes were acquired over a range
      of loading conditions both before and 1 year after successful valve surgery for
      long-term mitral regurgitation. To assess both left ventriculoarterial coupling
      to evaluate the interaction of the left ventricle with the arterial system with
      the use of the left ventricular contractile index, Ees, and effective arterial
      elastance, Ea. Left ventricular pump efficiency was expressed as the ratio of
      forward left ventricular stroke work to the corresponding pressure-volume area.
      All patients had successful mitral valve surgery as manifest by no or only
      trivial residual mitral regurgitation on physical examination and Doppler
      echocardiography. The average radionuclide regurgitant index of 1.28 +/- 0.56 was
      also less than the preoperative value of 2.70 +/- 0.80 (P < .0001). The mean left
      ventricular end-diastolic volume index decreased from 137 +/- 37 to 90 +/- 31
      mL/m2 (P < .001), and the average left ventricular end-systolic volume index also
      decreased (59 +/- 29 to 45 +/- 27 mL/m2, P < .01), although individual variation
      was observed. The average left ventricular ejection fraction fell from 0.58 +/-
      0.12 to 0.53 +/- 0.16, which was not significant. In contrast, Ees increased from
      a mean value of 0.95 +/- 0.66 mm Hg/mL during the preoperative study to 2.62 +/-
      2.16 mm Hg/mL at the 1-year postsurgical study (P < .01). This improvement in
      left ventricular contractility was observed in patients with long-term mitral
      regurgitation, who before surgery had preserved left ventricular ejection
      fraction (P < .001), less left ventricular dilation at end diastole (P < .01) and
      end systole (P < .001), and less impaired left ventricular contractility. Because
      effective arterial elastance was unchanged, left ventriculoarterial coupling also
      improved from an average of 0.47 +/- 0.39 to 1.81 +/- 1.63 (P < .01).
      Consequently, left ventricular pump efficiency improved from a mean preoperative
      value of 0.23 +/- 0.10 to 0.55 +/- 0.22 at the 1-year postsurgical study (P <
      .0001). CONCLUSIONS: The results indicate that left ventricular contractile
      impairment is reversible in many patients with long-term mitral regurgitation. In
      fact, these data indicate that mitral valve surgery can be recommended to
      preserve left ventricular contractility in patients with long-term mitral
      regurgitation, particularly in those patients who before surgery have normal left
      ventricular ejection fractions and less left ventricular dilation and contractile
      impairment.

PMID- 7641362
TI  - Pressure and volume loading of the right ventricle have opposite effects on left
      ventricular ejection fraction.
AB  - BACKGROUND: Left ventricular ejection fraction has been reported to be depressed
      in patients with right ventricular volume overload (RVVO) due to Ebstein's
      anomaly and uncomplicated atrial septal defect, whereas it is usually preserved
      in right ventricular pressure overload (RVPO) due to congenital pulmonic
      stenosis. In the present study, we examined the hypothesis that the differential
      timing of active displacement of the ventricular septum into the left ventricle
      in RVPO (end systole) and RVVO (end diastole) results in opposite effects of RVPO
      and RVVO on left ventricular ejection fraction. METHODS AND RESULTS: Ten patients
      with severe tricuspid regurgitation after tricuspid valve resection for
      endocarditis and 10 patients with primary pulmonary hypertension were studied as
      models of isolated RVVO and RVPO, respectively. Left ventricular ejection
      fraction, end-diastolic volume, and regional systolic shortening were measured
      with the use of echocardiographic techniques in these 20 patients and 10 healthy
      control subjects. In RVPO, despite marked underfilling of the left ventricle
      relative to the healthy control subjects (end-diastolic volume, 48 +/- 26 versus
      77 +/- 20 mL; P < .02), left ventricular ejection fraction was similar to that of
      the control subjects (56 +/- 5% versus 60 +/- 4%; P = .07) and only 1 of 10 RVPO
      patients had an ejection fraction of less than 50%. In contrast, in RVVO the left
      ventricle was volume replete (end-diastolic volume, 84 +/- 26 versus 77 +/- 20
      mL; P = NS), but left ventricular ejection fraction was significantly depressed
      (51 +/- 4% versus 60 +/- 4%, P < .001) compared with the control subjects, and 4
      of 10 RVVO patients had an ejection fraction of less than 50%. Analysis of
      systolic fractional shortening along two perpendicular short-axis diameters and
      the mutually orthogonal long axis demonstrated isolated augmentation of
      fractional shortening in the ventricular septal-to-posterolateral free wall
      dimension in RVPO (47.4 +/- 13.7% versus 34.2 +/- 13.1%, P < .05) and isolated
      depression of fractional shortening along that same dimension in RVVO (13.7 +/-
      11.8% versus 34.2 +/- 13.1%, P < .001) compared with the control subjects.
      CONCLUSIONS: End-systolic leftward ventricular septal shift in RVPO results in
      isolated augmentation of systolic shortening in the septal-to-free wall
      dimension, whereas end-diastolic leftward ventricular septal shift in RVVO
      results in isolated reduction in systolic shortening in the septal-to-free wall
      dimension. As a result, despite relative underfilling of the left ventricle in
      RVPO, resting left ventricular ejection fraction is preserved, whereas ejection
      fraction is depressed for the volume-replete left ventricle of patients with
      RVVO.

PMID- 7641363
TI  - Additive effects of combined angiotensin-converting enzyme inhibition and
      angiotensin II antagonism on blood pressure and renin release in sodium-depleted
      normotensives.
AB  - BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors do not decrease plasma
      angiotensin (Ang) II levels 24 hours after drug intake to the same extent as at
      peak. This intermittent partial "escape" is explained either by a renin-mediated
      reactive rise in plasma Ang I or by non-ACE-dependent Ang II generation. We
      therefore tested the hypothesis that a combination of ACE inhibition and Ang II
      blockade may have additive biological and hemodynamic effects. METHODS AND
      RESULTS: In a single-dose, double-blind, randomized, four-way, crossover study,
      an Ang II antagonist (losartan 50 mg), an ACE inhibitor (captopril 50 mg), their
      combination, and matched placebos were orally administered to 12 normotensive
      male volunteers maintained in mild sodium depletion. When captopril 50 mg and
      losartan 50 mg were given alone, the magnitude of their effects on blood
      pressure, plasma active renin, Ang I, and aldosterone was similar, whereas the
      kinetics of their effects were different, reflecting differences in drug
      pharmacokinetics. The losartan-captopril combination completely suppressed the
      rise in plasma Ang II induced by losartan 2 hours after drug intake (3.3 +/- 3.6
      pg/mL versus 20.3 +/- 19.1 pg/mL, respectively, P < .05). Six hours after drug
      intake, the losartan-captopril combination induced a significantly greater
      decrease in mean blood pressure than that produced by either losartan or
      captopril alone (73 +/- 7 mm Hg versus 79 +/- 8 mm Hg versus 81 +/- 7 mm Hg,
      respectively, P < .05). The maximum placebo-subtracted falls in mean blood
      pressure for the losartan-captopril combination, captopril 50 mg, and losartan 50
      mg were 14 +/- 5 mm Hg, 10 +/- 3 mm Hg, and 9 +/- 6 mm Hg, respectively (F2.22 =
      3.45, P < .05). The duration of the mean blood pressure fall was not prolonged by
      the combination. After combined losartan-captopril administration, the area under
      the plasma active renin versus time curve (0 to 24 hours) was significantly
      increased when compared with either losartan or captopril alone (6404 +/- 2961
      pg.h.mL-1 versus 3105 +/- 1461 pg.h.mL-1 versus 2092 +/- 867 pg.h.mL-1,
      respectively, P < .05). The combination had no additive effects on plasma
      aldosterone decrease when compared with either losartan or captopril alone (58 +/
      17% versus 51 +/- 20% versus 53 +/- 21%, respectively, NS). CONCLUSIONS: The
      combined administration of a standard single oral dose of an ACE inhibitor and an
      Ang II antagonist to mildly sodium-depleted normal subjects (1) had a major
      additive effect on plasma renin rise, (2) induced an additional mean blood
      pressure reduction, and (3) had no additive effect on plasma aldosterone fall.

PMID- 7641364
TI  - Left atrial size and the risk of stroke and death. The Framingham Heart Study.
AB  - BACKGROUND: The medical literature contains conflicting reports on the
      association of left atrial (LA) enlargement with risk of stroke. The relation of
      LA size to risk of stroke and death in the general population remains largely
      unexplored. METHODS AND RESULTS: Subjects 50 years of age and older from the
      Framingham Heart Study were studied to assess the relations between
      echocardiographic LA size and risk of stroke and death. During 8 years of follow
      up, 64 of 1371 (4.7%) men and 73 of 1728 (4.2%) women sustained a stroke, and 296
      (21.6%) men and 271 (15.7%) women died. Sex-specific Cox proportional-hazards
      models were adjusted for age, hypertension, diabetes, atrial fibrillation,
      smoking, ECG left ventricular (LV) hypertrophy, and congestive heart failure or
      myocardial infarction. After multivariable adjustment, for every 10-mm increase
      in LA size, the relative risk of stroke was 2.4 in men (95% CI, 1.6 to 3.7) and
      1.4 in women (95% CI, 0.9 to 2.1); the relative risk of death was 1.3 in men (95%
      CI, 1.0 to 1.5) and 1.4 in women (95% CI, 1.1 to 1.7). Adjusting for ECG LV
      mass/height attenuated the relation of LA size to stroke and death. CONCLUSIONS:
      After multivariable adjustment, LA enlargement remained a significant predictor
      of stroke in men and death in both sexes. The relation of LA enlargement to
      stroke and death appears to be partially mediated by LV mass.

PMID- 7641365
TI  - Assessment of cardiac function by three-dimensional echocardiography compared
      with conventional noninvasive methods.
AB  - BACKGROUND: Reliable, serial, noninvasive quantitative estimation of left
      ventricular ejection fraction is essential for selecting and timing therapeutic
      interventions in patients with heart disease. Equilibrium radionuclide
      angiography is widely used for this purpose but has well-recognized limitations.
      Advantages of echocardiography over equilibrium radionuclide angiography include
      assessment of wall motion, valvular pathology, and cardiac hemodynamics, in
      addition to portability, lack of radiation exposure, and substantially lower
      cost. However, conventional echocardiographic techniques are limited by geometric
      assumptions, image positioning errors, and use of subjective visual methods. To
      overcome these limitations, a three-dimensional echocardiographic method was
      developed. This study compares ejection fraction by three-dimensional
      echocardiography, quantitative two-dimensional echocardiography, and subjective
      two-dimensional echocardiographic visual estimation with that by equilibrium
      radionuclide angiography. METHODS AND RESULTS: Fifty-one unselected patients with
      suspected heart disease underwent left ventricular ejection fraction
      determination by equilibrium radionuclide angiography and three-dimensional
      echocardiography using an interactive line-of-intersection display and a new
      algorithm, ventricular surface reconstruction, for volume computation. In 44
      patients, ejection fractions were also estimated visually by experienced
      observers from two-dimensional echocardiography and by quantitative two
      dimensional echocardiography using an apical biplane summation-of-disks
      algorithm. An excellent correlation was obtained between three-dimensional
      echocardiography and equilibrium radionuclide angiography (r = .94 to .97, SEE =
      3.64% to 5.35%; limits of agreement, 10.3% to 13.3%) without significant
      underestimation or overestimation. SEE values and limits of agreement were
      twofold to threefold lower than corresponding values for all two-dimensional
      echocardiographic techniques. In addition, interobserver variability was
      significantly lower for the three-dimensional echocardiographic method (10.2%)
      than for the apical biplane summation-of-disks method (26.1%) and subjective
      visual estimation (33.3%). CONCLUSIONS: Determination of ejection fraction by
      three-dimensional echocardiography yields results comparable to those obtained by
      equilibrium radionuclide angiography and is substantially superior to all two
      dimensional echocardiographic methods. Therefore, three-dimensional
      echocardiography may be used for accurate serial quantification of left
      ventricular function as an alternative to equilibrium radionuclide angiography.

PMID- 7641366
TI  - Transesophageal echocardiographic assessment of mitral valve position and
      pulmonary venous flow during cardiopulmonary resuscitation in humans.
AB  - BACKGROUND: The mechanisms of blood flow during closed-chest cardiopulmonary
      resuscitation (CPR) in humans have been debated since the technique was first
      described in 1960. Two competing models, the cardiac pump theory and the thoracic
      pump theory, have been proposed, and some investigators have used mitral valve
      position during the downstroke of chest compression to distinguish between them.
      Previous studies using either transthoracic or transesophageal echocardiography
      have yielded conflicting results, and there have been few, if any, hemodynamic or
      echocardiographic studies on pulmonary venous flow (PVF) during CPR. METHODS AND
      RESULTS: In this study, transesophageal two-dimensional and pulsed Doppler
      echocardiography were used to study mitral valve position and flow, together with
      PVF, in 20 adult patients undergoing manual CPR. In the 17 patients who could be
      analyzed, the mitral valve closed in 5 patients (group 1) during chest
      compression but stayed open or opened further in the remaining 12 patients (group
      2). Peak forward mitral flow occurred during the release phase in group 1 but
      during the compression phase in group 2. During chest compression, PVF occurred
      in the forward direction (from the pulmonary vein to the left atrium) in 8 of the
      group 2 patients (group 2a) and in the backward direction (from the left atrium
      to the pulmonary vein) in all group 1 patients and the remaining 4 patients in
      group 2 (group 2b). The downtime (time from collapse to CPR) was significantly
      shorter (P < .05) for those in group 1 (7.0 +/- 4.4 minutes) than in groups 2a
      (19.8 +/- 7.7 minutes) and 2b (17.8 +/- 6.8 minutes). CONCLUSIONS:
      Transesophageal echocardiography performed during manual CPR in humans disclosed
      three different patterns of mitral valve position and PVF during chest
      compression. The presence of an opened mitral valve with forward mitral flow and
      backward pulmonary venous flow during chest compression in a small number of
      subjects underscores this heterogeneity in blood flow and suggests the possible
      existence of a "left atrium pump" in addition to the currently known "left
      ventricle pump" and "chest pump" mechanisms.

PMID- 7641367
TI  - Frequency of hypoxanthine guanine phosphoribosyltransferase (HPRT-) T cells in
      the peripheral blood of cardiac transplant recipients. A noninvasive technique
      for the diagnosis of allograft rejection.
AB  - BACKGROUND: Histological evaluation of serial endomyocardial biopsies performed
      at fixed time intervals after cardiac transplantation is the universal method
      used for the detection of cardiac rejection and assessment of the adequacy of
      antirejection therapy. No noninvasive methodology thus far investigated has
      achieved a high enough sensitivity and predictive accuracy to be considered as a
      potential replacement for endomyocardial biopsy in the detection of rejection in
      adults. The present study exploited the finding that the rate of spontaneous
      mutation in the hypoxanthine guanine phosphoribosyltransferase (HPRT) gene is
      higher in proliferating human T cells than in resting cells. Thus, it was
      reasoned that in the posttransplantation setting, the frequency of HPRT- cells in
      peripheral blood may provide an indirect measure of alloactivated T lymphocytes.
      METHODS AND RESULTS: This study consisted of determining the clonal frequency of
      HPRT- mutant cells (FMC/10(6) peripheral blood mononuclear cells [PBMCs]) within
      a total of 293 peripheral blood samples representing various numbers of
      sequential samples from each of 27 transplant recipients. These sequential
      samples represented time periods when endomyocardial biopsy specimens showed
      either (1) no evidence of rejection (n = 5 patients), (2) a single initial
      episode after transplantation of early (< 1 year) or late (> 1 year) rejection (n
      = 12 patients), or (3) multiple rejection episodes (n = 10 patients). Statistical
      analyses were used to quantify the time profiles of FMC/10(6) PBMCs in serial
      samples among transplant recipients and to determine the association of these
      profiles with both the onset of first rejection episodes and, in appropriate
      patients, the recurrence of rejection episodes. Data showed that PBMCs from
      patients with no evidence of rejection uniformly gave low values of < 6 FMC/10(6)
      cells, a frequency similar to that seen in healthy nontransplanted volunteers. In
      contrast, 19 of the 22 PBMC samples that were obtained from patients whose
      corresponding biopsy sample was diagnosed with a histological rejection grade of
      > or = 3 gave values of > 6 FMC/10(6) cells, 11 of which gave values > 50/10(6)
      cells (range, 146 to 46,982 FMC/10(6) cells). A significant association between
      the onset of first rejection and an increased rate of FMC/10(6) values was noted
      (P = .0001). The ability of a rising trend in FMC/10(6) values to correctly
      identify the onset of rejection was 81.8% and to correctly identify no rejection,
      100%. In addition, a significant association between recurrent rejection episodes
      and persistence of high FMC/10(6) values in the weeks after treated rejection
      episodes was noted (P = .0003). The ability of a persistently elevated trend in
      values of FMC/10(6) cells to correctly identify recurrent rejection was 90% and
      to correctly identify no rejection, 100%. CONCLUSIONS: Increasing frequencies of
      HPRT- mutant cells in peripheral blood correlated with the onset of first
      rejection, and persistently elevated HPRT- mutant cells in the weeks after a
      treated rejection episode correlated with recurrent rejection. This quantitative
      noninvasive assay may thus serve as a useful adjunct to endomyocardial biopsy for
      monitoring post-cardiac transplantation patients, and its use as a prospective
      diagnostic tool merits further study.

PMID- 7641368
TI  - Effect of increased drive-train stimulus intensity on dispersion of ventricular
      refractoriness.
AB  - BACKGROUND: Most studies evaluating the effects of high-intensity drive-train
      (S1) stimulation on the measurement of the ventricular effective refractory
      period (VERP) demonstrated a shortening of the VERP. Because this effect may be
      due to the local release of catecholamines, VERP shortening would be expected to
      occur only near the site of stimulation. Local shortening in the VERP should then
      result in an increased dispersion of refractoriness during high-intensity drive
      train stimulation. Thus, this study evaluated the spatial distribution of the
      VERP shortening resulting from high-intensity S1 stimulation and its effect on
      dispersion of refractoriness. METHODS AND RESULTS: Three groups of patients were
      studied. In group 1, 10 subjects without structural heart disease had VERP
      determinations performed at the right ventricular apex (RVA) and outflow tract
      (RVOT) while the S1 site was changed to evaluate the effects of low-intensity S1
      stimulation on the measured VERP. In group 2, the effect of high-intensity S1
      stimulation on the VERP was studied 0, 7, 14, and 21 mm away from the S1 site to
      measure the spatial distribution of VERP shortening and the effect on dispersion
      of refractoriness; 10 additional subjects without structural heart disease made
      up group 2. Because increased dispersion of refractoriness may be deleterious in
      certain clinical situations, the effect of high-intensity S1 stimulation was
      studied in group 3, which comprised 10 subjects with chronically implanted
      transvenous defibrillators; noninvasive measurements of the VERP through the
      chronic lead were made while the S1 stimulus intensity was varied from low to
      high intensity. All VERP determinations were performed during continuous pacing
      by use of an incremental method and a low stimulus intensity for the
      extrastimulus. In group 1, the RVA VERPs were 218 +/- 9 and 214 +/- 10 ms when
      the S1 site was the RVA and RVOT, respectively (P = NS). The RVOT VERPs were also
      unchanged when the S1 site was changed from the RVOT to the RVA. In group 2, high
      intensity S1 changed the VERP from 224 +/- 8 (at twice the threshold) to 203 +/-
      10 ms (P < .01), 220 +/- 11 to 209 +/- 12 ms (P < .01), 222 +/- 12 to 221 +/- 12
      ms, and 220 +/- 11 to 221 +/- 11 ms at 0, 7, 14, and 21 mm away from the S1 site,
      respectively. High-intensity S1 stimulation led to an increase in the dispersion
      of refractoriness from 13 +/- 4 to 22 +/- 9 ms (P = .006). In group 3, high
      intensity S1 stimulation shortened the VERP from 309 +/- 23 to 285 +/- 30 ms (P =
      .0003). CONCLUSIONS: Low-intensity S1 stimulation has no significant effect on
      the VERP. High-intensity S1 stimulation shortens the refractory period maximally
      at the site of stimulation; the VERP shortening dissipates between 7 and 14 mm
      away from the site of S1 stimulation, resulting in an increased dispersion of
      refractoriness. The local VERP shortening with high-intensity stimulation is
      noted in patients with chronically implanted defibrillator leads, which may have
      implications for the mechanism of proarrhythmia during high-intensity
      stimulation.

PMID- 7641369
TI  - Endovascular stents in the pulmonary circulation. Clinical impact on management
      and medium-term follow-up.
AB  - BACKGROUND: The use of endovascular stents to relieve obstructions in the setting
      of non-balloon dilatable pulmonary artery stenosis has been encouraging. The
      benefits in management and the potential for restenosis, however, have not been
      defined. This study attempts to assess the impact of such implants on clinical
      outcomes and the pattern of stent incorporation within the vessel wall. METHODS
      AND RESULTS: Fifty-five balloon-expandable stents were implanted in 42 patients
      6.1 +/- 4.7 years of age. Patients were followed prospectively (median, 15
      months) and recatheterized 1 year after implantation. Thirty-eight patients had
      the implants positioned percutaneously (49 implants), while 4 patients (6
      implants) had intraoperative implantations. There was a diameter increase in the
      stenotic area of 109 +/- 79% (P < .0001) and a gradient reduction of 74 +/- 26%
      (P < .0001). Twelve stents straddled the orifice of side-branch pulmonary
      arteries and reduced flow to the branch vessel acutely in 7 patients. Twenty-nine
      patients underwent recatheterization, and various degrees and locations of
      acquired intraluminal narrowing were observed in all cases, particularly in areas
      of diameter mismatch between the stented and nonstented vessels. Eleven patients
      had further dilation with diameter improvement. Of the 38 patients who underwent
      percutaneous implantation, planned surgery for pulmonary artery stenosis was
      avoided in 33 and deferred in 4 patients. One patient who was considered
      inoperable had stent implantation as a palliative procedure. Symptomatic
      improvement was reported in 27 patients, and 15 patients remained asymptomatic.
      CONCLUSIONS: Endovascular stents have a role in the treatment of pulmonary artery
      stenoses and positively affect clinical care. The stenosis relief, however, may
      be tempered by the development of intraluminal stent obstruction, which may
      require redilation (15 of 55 stents) and mandates long-term follow-up.

PMID- 7641370
TI  - Quantitative morphometric analysis of progressive infundibular obstruction in
      tetralogy of Fallot. A prospective longitudinal echocardiographic study.
AB  - BACKGROUND: The morphological hallmark of tetralogy of Fallot is controversial,
      with much disagreement as to whether the subpulmonary infundibulum in this lesion
      is hypoplastic. In addition, few quantitative data are available regarding the
      morphometry of the subpulmonary infundibulum, what anatomic characteristics are
      acquired in the postnatal period, and at what rate they progress. We also sought
      to determine whether echocardiographic morphometric analysis of the infundibulum
      can predict clinical course in infants with tetralogy of Fallot. METHODS AND
      RESULTS: Twenty-one infants with tetralogy of Fallot (median age at initial
      study, 1.6 months) were prospectively followed with serial echocardiograms until
      the time of first surgical intervention (median age at surgery, 10 months).
      Selected video still frames were digitized off-line with a computerized system.
      Compared with age-matched normal control infants (n = 37), the following indexed
      infundibular dimensions in patients with tetralogy of Fallot were significantly
      smaller: length (1.86 +/- 0.54 versus 2.7 +/- 0.56 cm/BSA0.5, P < .0001), cross
      sectional area (1.6 +/- 0.49 versus 4.7 +/- 1.3 cm2/BSA, P < .0001), and volume
      (1.24 +/- 0.62 versus 7.2 +/- 3 mL/BSA1.5, P < .0001). The following measurements
      were increased in tetralogy patients: infundibular septal thickness (0.83 +/-
      0.21 versus 0.54 +/- 0.06 cm/BSA0.5, P = .0002) and infundibular free-wall
      thickness (0.62 +/- 0.13 versus 0.49 +/- 0.06 cm/BSA0.5, P = .006). The angle
      between infundibular septum and ventricular septum had a greater degree of
      anterosuperior deviation in tetralogy patients, resulting in a larger
      infundibuloventricular septal angle (77 +/- 8.2 degrees versus 31 +/- 6.5
      degrees, P < .0001). During follow-up, infundibular volume in tetralogy patients
      decreased from 1.24 +/- 0.62 to 0.81 +/- 0.47 mL/BSA1.5 (P = .002), correlating
      with infundibular septal thickness (r = -.63, P < .003). The mean rate of
      decrease of indexed infundibular volume was 0.1 +/- 0.13 mL.BSA-15.mo-1.
      Correlation analysis revealed a nonlinear correlation between the degree of
      infundibular septal malalignment and indexed infundibular volume (r = .93, P <
      .0001). Tetralogy patients who required early surgical intervention (4.8 +/- 0.9
      versus 10.7 +/- 1.7 months, P < .0001) had a smaller infundibulum at presentation
      (0.92 +/- 0.35 versus 1.41 +/- 0.67 mL/BSA1.5, P = .04) and an accelerated rate
      of infundibular narrowing (0.17 +/- 0.18 versus 0.06 +/- 0.08 mL.BSA-1.5.mo-1, P
      = .04). CONCLUSIONS: Compared with normal infants, the subpulmonary infundibulum
      in tetralogy of Fallot is characterized by a smaller volume, shorter and thicker
      infundibular septum, and anterosuperior deviation of the infundibular septum.
      Infundibular obstruction in tetralogy patients is progressive, with an average
      rate of decrease in indexed infundibular volume of 0.1 +/- 0.13 mL.BSA-1.5.mo-1.
      Infants who are likely to require early therapeutic intervention may be
      identified on their initial echocardiogram as having an infundibular volume of <
      0.9 to 1.0 mL/BSA1.5.

PMID- 7641371
TI  - Repeat dilation of intravascular stents in congenital heart defects.
AB  - BACKGROUND: Intravascular (Palmaz) stents have been successfully implanted in
      patients with congenital and acquired branch pulmonary stenosis. Early results
      are excellent; however, there is no information on restenosis and repeat dilation
      in patients with congenital heart disease. The purpose of this study is to review
      the incidence of restenosis and demonstrate the safety and efficacy of repeat
      dilation of stents in this group of patients. METHODS AND RESULTS: Of 94 patients
      with 163 implanted stents in this single-center study, 43 patients with 73
      implanted stents underwent recatheterization. Only 2 of 73 restudied stents (3%)
      developed significant restenosis. In 20 patients, 30 stents were redilated. At
      stent implantation, the mean age of this subgroup was 14.2 years, the mean
      intraluminal diameter increased from 4.9 to 10.7 mm (P = .0001), and the systolic
      gradient (mean) across the stent decreased from 52 to 11 mm Hg (P = .0001). At
      recatheterization (mean, 13 months), all stents were patent. The mean diameter
      decreased by 1.2 mm (P = .0001), but the increase in the gradient (mean, 3 mm Hg)
      was not significant (P = .11). After repeat dilation, the diameter increased from
      9.5 to 12.2 mm (P = .0001), and the gradient decreased from 14 to 8 mm Hg (P =
      .0003). The 2 stents with restenosis were redilated successfully. Two patients
      underwent a successful second redilation of 3 stents at 18 and 26 months. There
      were no complications. CONCLUSIONS: All stents remained patent. The occurrence of
      significant restenosis is low (3%), and these restenoses can be redilated and/or
      restented. Repeat dilation of the Palmaz stent implanted in branch pulmonary
      artery stenosis can be performed with safety and efficacy (94% success rate) up
      to 3 years after stent implantation.

PMID- 7641372
TI  - Dietary correction of hypercholesterolemia in the rabbit normalizes endothelial
      superoxide anion production.
AB  - BACKGROUND: We have shown that hypercholesterolemia increases vascular superoxide
      anion (O2-) production, which could be responsible for augmented inactivation of
      endothelium-derived vascular relaxing factor. We sought to determine whether this
      increased vascular O2- production is due to infiltration of macrophages into the
      intima and whether dietary treatment of hypercholesterolemia normalizes O2-
      production. METHODS AND RESULTS: A specific and sensitive assay for O2- based on
      chemiluminescence of lucigenin was used; the amount of O2- produced by vascular
      ring segments was quantified based on known quantities of O2- produced by
      xanthine-xanthine oxidase standards. O2- production of aortic segments from
      normal rabbits (n = 9), cholesterol-fed rabbits (1% cholesterol diet for 1 month,
      n = 7), and rabbits fed a 1% cholesterol diet for 1 month followed by a normal
      diet for 1 month (regression rabbits, n = 5) was measured. At the end of these
      diets, serum cholesterol levels were 1.5 +/- 0.2, 26.0 +/- 3.9, and 1.8 +/- 0.5
      mmol/L (58 +/- 6, 1000 +/- 150, and 71 +/- 19 mg/dL) in the normal, cholesterol
      fed, and regression animals, respectively. Vessels from normal rabbits with
      endothelium produced 0.32 +/- 0.06 nmol O2-/mg dry wt per minute, whereas those
      without endothelium produced approximately twice as much O2- (0.66 +/- 0.12 nmol
      O2- mg dry wt per minute. Vessels with endothelium from cholesterol-fed rabbits
      produced 4.5-fold more O2- than vessels from normal animals. This increased
      production of O2- was normalized by endothelial removal. This increased
      production of O2- was not due to infiltration of macrophages in the intima,
      because there was no correlation between vascular O2- production and macrophage
      infiltration assessed by immunohistochemistry with use of a specific antibody
      against rabbit macrophage. O2- production by vessels from regression rabbits was
      similar to that observed in normal animals, and as in the normal rabbits,
      endothelial removal increased O2- production. Aortic rings from these animals
      also were studied in organ chambers. Dietary lowering of cholesterol dramatically
      improved vasodilator responses to acetylcholine and A23187 (P < .05 versus
      cholesterol-fed rabbits). CONCLUSIONS: Dietary lowering of cholesterol not only
      improves endothelium-dependent vascular relaxation but also normalizes
      endothelial O2- production. Decreases of O2- production by dietary lowering of
      cholesterol not only may improve vasomotor control but also may improve other
      aspects of vascular integrity in atherosclerosis.

PMID- 7641373
TI  - Accumulation of fetal fibronectin mRNAs after balloon denudation of rabbit
      arteries.
AB  - BACKGROUND: Fibronectin (FN), a component of the extracellular matrix, influences
      cellular migration and differentiation. It is a prominent component of the
      extracellular matrix of normal arteries and is thought to play an important role
      in the pathogenesis of restenosis after angioplasty. FN exists in multiple forms
      that arise from a single RNA transcript that can be alternatively spliced. EIIIA-
      and EIIIB-containing FN mRNAs predominate in the embryo, whereas in the adult,
      most of the normal tissue FN lacks these domains. Since few data were available
      concerning pattern of expression of the different alternatively spliced forms of
      FN mRNA in arteries after endoluminal injury, we analyzed the expression of EIIIA
      and EIIIB FN isoforms at different times after experimental angioplasty. METHODS
      AND RESULTS: The spatial and temporal alterations in FN expression were studied
      in an in vivo model of endothelial denudation in the rabbit aorta and iliac
      artery by a combination of immunochemistry and in situ hybridization methods.
      Alternatively spliced forms of FN EIIIA and EIIIB were detected in the media and
      the adventitia of both types of vessels 24 to 48 hours after injury. Two weeks
      after injury, EIIIA and EIIIB mRNAs were found to accumulate within the luminal
      layers of the neointima. The cellular form of FN protein was not found until 2
      weeks after the injury and accumulated in the inner part of the neointima.
      CONCLUSIONS: These data demonstrate that FN upregulation is an early and long
      lasting process after arterial injury. These results suggest that the induction
      of the embryonic FN isoforms may be involved in the restenotic process that
      follows balloon denudation of arteries.

PMID- 7641374
TI  - Myocardial protection by Na(+)-H+ exchange inhibition in ischemic, reperfused
      porcine hearts.
AB  - BACKGROUND: Studies in isolated myocytes and isolated heart preparations have
      suggested that Na(+)-H+ exchange is an important mechanism for myocardial
      ischemia-reperfusion injury. This study was undertaken to determine whether
      inhibition of Na(+)-H+ exchange limits infarct size and improves regional
      systolic shortening in regional ischemia and reperfusion in intact pigs. METHODS
      AND RESULTS: The left anterior descending coronary artery was occluded in 18
      anesthetized and thoracotomized pigs for 45 minutes and then reperfused for 24
      hours. As main end points of this study, regional systolic shortening
      (sonomicrometry) and infarct size (percentage of infarcted to ischemic
      myocardium) were determined at the end of the experiments. Infarcted myocardium
      was assessed by histochemistry (tetrazolium stain) and by quantitative histology
      of one heart slice. The Na(+)-H+ exchange inhibitor Hoe 694 was administered
      intravenously at a dose of 3 mg/kg in 6 pigs each either 10 minutes before
      ischemia (group A) or 10 minutes before the onset of reperfusion (group B). Six
      pigs served as controls (group C). Treatment with Hoe 694 before ischemia
      decreased histochemical infarct size from 65 +/- 18% (control group) to 13 +/- 8%
      (P < .01) and histological infarct size from 49 +/- 20% (control group) to 14 +/-
      4% (P < .01). Histochemical (55 +/- 19%) and histological (42 +/- 15%) infarct
      sizes of group B were insignificantly reduced by 15%. Myocardial protection in
      group A was associated with an attenuated contracture after 10 minutes of
      reperfusion and an improved regional systolic shortening after 24 hours of
      reperfusion (group A, 25 +/- 12%; control group, 6 +/- 5%; P = .01). These
      parameters remained unaffected in group B. CONCLUSIONS: This study clearly
      demonstrates that Na(+)-H+ exchange is an important mechanism for cell death in
      myocardial ischemia and reperfusion in intact pigs; thus, inhibition of this
      exchange system may prove a promising new strategy in the clinical treatment of
      myocardial ischemia and reperfusion.

PMID- 7641375
TI  - Chronic hypoxia differentially regulates alpha 1-adrenergic receptor subtype
      mRNAs and inhibits alpha 1-adrenergic receptor-stimulated cardiac hypertrophy and
      signaling.
AB  - BACKGROUND: After myocardial ischemia and/or infarction, surviving cardiac
      myocytes in and around the injured zone develop hypertrophy to compensate for the
      loss of contractile units due to myocyte injury and death. One of the factors
      that may be involved in the development of hypertrophy after ischemic injury is
      norepinephrine (NE), an agent that induces hypertrophy of cardiac myocytes
      through the alpha 1-adrenergic receptor (AR). It is not known, however, whether
      hypoxia, a major component of ischemia, has any direct effect on NE-stimulated
      hypertrophy. Therefore, we sought to determine whether chronic hypoxia could
      alter NE-stimulated hypertrophy and if so, whether this alteration was related to
      alpha 1-AR-mediated signaling and alpha 1-AR changes at both the protein and mRNA
      levels. METHODS AND RESULTS: We developed a model of chronic hypoxia in cultured
      neonatal rat cardiac myocytes in which myocytes were exposed to 1% oxygen for 72
      hours. Initially, we observed that chronic hypoxia inhibited NE-stimulated
      hypertrophy, as reflected by decreases in both new protein synthesis and total
      protein content during chronic hypoxia. Then we found that chronic hypoxia also
      inhibited alpha 1-AR-transduced phosphatidylinositol hydrolysis, as indicated by
      a reduction in alpha 1-AR-stimulated inositol phosphate production in hypoxic
      cells. These observations suggested that the inhibition of NE-stimulated
      hypertrophy seen during chronic hypoxia was due to impairment of alpha 1-AR
      mediated signaling and could result from changes in alpha 1-AR numbers and/or
      subtype distribution. To address this issue, we determined alpha 1-AR density and
      subtype distribution by radioligand binding and alpha 1-AR subtype mRNAs,
      including alpha 1A/D-, alpha 1B-, and alpha 1C-ARs, by RNase protection assays.
      We found that chronic hypoxia differentially regulated both the pharmacologically
      defined alpha 1-AR subtypes and the mRNAs for the alpha 1-AR subtypes. Thus,
      hypoxia for 72 hours coordinately downregulated both the pharmacologically
      defined alpha 1A-AR density and the alpha 1C-AR mRNA level. During normoxia, NE
      increased the pharmacologically defined alpha 1A-AR density and the alpha 1C-AR
      mRNA level, but hypoxia for 72 hours prevented these NE-mediated changes.
      CONCLUSIONS: Chronic hypoxia (1) inhibits alpha 1-AR-mediated hypertrophy of
      cardiac myocytes and alpha 1-AR-transduced phosphatidylinositol hydrolysis and
      (2) downregulates both the pharmacologically defined alpha 1A-AR density and the
      alpha 1C-AR mRNA level.

PMID- 7641376
TI  - Impact of left ventricular unloading after late reperfusion of canine anterior
      myocardial infarction on remodeling and function using isosorbide-5-mononitrate.
AB  - BACKGROUND: Late reperfusion during acute myocardial infarction results in
      delayed recovery of ventricular function and less remodeling, whereas ventricular
      unloading with nitrates improves function and attenuates remodeling. Whether late
      reperfusion combined with prolonged unloading with isosorbide-5-mononitrate
      (ISMN) might produce greater functional recovery and less remodeling than late
      reperfusion alone is not known. METHODS AND RESULTS: In vivo left ventricular
      function and topography (echocardiograms), postmortem topography (planimetry),
      and collagen (hydroxyproline) were measured in dogs that were randomized to
      reperfusion 2 hours after left anterior descending coronary artery ligation, and
      ISMN (n = 12) or placebo (n = 12) was given as 25 mg IV over 4 hours followed by
      50 mg PO QID for 6 weeks. Compared with placebo, the ISMN group had similar heart
      rate but lower left atrial pressure, mean arterial pressure, and rate-pressure
      products. Although in vivo baseline remodeling and functional parameters were
      similar in the two groups, by 6 weeks the ISMN group had smaller (P < or = .05)
      infarct and noninfarct segment lengths, ventricular volumes, and mass; less (P <
      .001) asynergy; and greater (P < .001) ejection fraction. More important, by 2
      days, ejection fraction was 18% greater (P < .025) and asynergy 26% less (P <
      .05) with ISMN. At 6 weeks, ISMN showed less (P < or = .05) scar size, scar
      collagen, cavity dilation, noninfarct wall thickness, and apical bulging than
      placebo. In another 4 dogs, acute ISMN produced less improvement in function and
      remodeling than prolonged ISMN. CONCLUSIONS: Late reperfusion of acute anterior
      myocardial infarction combined with prolonged ISMN unloading results in greater
      and earlier recovery of ventricular function and less remodeling than late
      reperfusion alone.

PMID- 7641377
TI  - Infarct salvage with liposomal prostaglandin E1 administered by intravenous bolus
      immediately before reperfusion in a canine infarction-reperfusion model.
AB  - BACKGROUND: Prostaglandin E1 (PGE1) inhibits leukocyte and platelet function and
      reduces infarct size during left atrial infusion. Intravenous liposomal PGE1 (TLC
      C-53) accelerates thrombolysis and prevents reocclusion in canine coronary
      thrombosis. We tested the hypothesis that intravenous TLC C-53 would attenuate
      reperfusion injury in a canine infarction-reperfusion model. METHODS AND RESULTS:
      Twenty-one open-chest dogs were randomized to receive a 10-minute intravenous
      infusion of either liposome diluent (placebo), free PGE1 (2 micrograms/kg), or
      TLC C-53 (2 micrograms/kg PGE1) after 2 hours of left anterior descending (LAD)
      occlusion just before reperfusion. Hemodynamic assessment, regional myocardial
      blood flow determination with radioactive microspheres, myocardial leukocyte
      infiltration by myeloperoxidase assay, and estimation of infarct size using
      triphenyl tetrazolium chloride staining were performed. Regional fractional
      shortening was measured with sonomicrometer crystals implanted in the
      midmyocardium. Infarct size as a percentage of the risk region was significantly
      reduced (P < .05) with TLC C-53 (37.9 +/- 17.4%) compared with PGE1 (56.7 +/-
      13.9%) or placebo (58.0 +/- 9.9%) infusion. Infarct salvage with TLC C-53 was
      independent of collateral blood flow by ANCOVA. There was a dramatic reduction in
      myeloperoxidase activity in the infarct, risk, and border regions of dogs treated
      with TLC C-53 compared with placebo. Enzyme activity was also significantly
      reduced (P < .05) in the infarct zone with TLC C-53 (0.11 +/- 0.1 U/100 mg)
      treatment compared with PGE1 (0.38 +/- 0.3 U/100 mg). No significant differences
      in regional myocardial blood flow or myocardial function among treatment groups
      were identified, although there was a trend toward improved function in the TLC C
      53 dogs. CONCLUSIONS: Bolus intravenous administration of TLC C-53 immediately
      before reperfusion results in reduced leukocyte infiltration and substantial
      infarct salvage. TLC C-53 mah be useful in limiting reperfusion injury during
      treatment of acute myocardial infarction.

PMID- 7641378
TI  - Maintenance of coronary patency after fibrinolysis with tissue factor pathway
      inhibitor.
AB  - BACKGROUND: Pharmacological coronary fibrinolysis induces procoagulant effects
      that contribute to delayed recanalization and early reocclusion. This study was
      designed to determine whether brief inhibition of activation of the coagulation
      cascade with tissue factor pathway inhibitor, a physiological inhibitor of
      activated factor X and its activation by the tissue factor/factor VII complex,
      would facilitate fibrinolysis, sustain patency of recanalized arteries, or both.
      METHODS AND RESULTS: Platelet-rich coronary thrombi were induced with anodal
      current that elicited intimal injury in 21 conscious dogs. Each was randomized to
      human recombinant tissue-type plasminogen activator (rTPA 1.0 mg/kg IV over 1
      hour) with infusion of 50 micrograms.kg-1.min-1 of human recombinant tissue
      factor pathway inhibitor (rTFPI, n = 7), 100 micrograms.kg-1.min-1 of rTFPI (n =
      8), or 300 mmol/L arginine phosphate buffer as a control (n = 6) concomitant with
      and for 1 hour after infusion of the plasminogen activator. Recanalization,
      verified with proximal Doppler flow probes, occurred in all but 1 dog given the
      high dose of rTFPI. It was not accelerated by conjunctive rTFPI. Reocclusion
      occurred within 90 minutes after infusion of rTPA in all 6 control dogs. However,
      reocclusion was delayed and patency was sustained for the entire 24-hour
      observation interval in 2 of 6 dogs (excluding 1 that did not survive) given the
      low dose and in 4 of 6 dogs (excluding 1 that did not receive the desired amount)
      given the high dose of rTFPI (P < .05 compared with controls). Cyclic flow
      variations indicative of platelet aggregation and disaggregation locally were
      virtually eliminated by rTFPI (3 +/- 4[SD]/h in dogs given the low dose and 2 +/-
      2/h in those given the high dose of rTFPI compared with 13 +/- 12/h in controls,
      P < .05). In addition, rTFPI increased activated partial thromboplastin time and
      prothrombin time only at the high dose (1.4 +/- 0.3 and 2.1 +/- 0.9 times
      baseline) and had no effects on platelet aggregation assayed ex vivo and only
      minimal effects on bleeding time assayed in vivo. CONCLUSIONS: Brief inhibition
      of the coagulation system by administration of rTFPI sustains patency of arteries
      recanalized by pharmacological fibrinolysis without markedly perturbing
      hemostatic mechanisms.

PMID- 7641379
TI  - Beneficial effects of inhibition of angiotensin-converting enzyme on ischemic
      myocardium during coronary hypoperfusion in dogs.
AB  - BACKGROUND: Angiotensin-converting enzyme (ACE) produces angiotensin II, causing
      vasoconstriction of coronary arteries and reduction of coronary blood flow. The
      present study was undertaken to test the hypothesis that an ACE inhibitor
      increases coronary blood flow and improves myocardial metabolic and contractile
      functions of ischemic myocardium. METHODS AND RESULTS: In 65 open-chest dogs, the
      left anterior descending coronary artery was perfused through an extracorporeal
      bypass tube from the left carotid artery. When cilazaprilat (3 micrograms/kg per
      minute) was infused into the bypass tube for 10 minutes after reduction of
      coronary blood flow due to partial occlusion of the bypass tube, coronary blood
      flow increased from 30 +/- 1 to 43 +/- 2 mL/100 g per minute despite there being
      no changes in coronary perfusion pressure (43 +/- 1 mm Hg). The ratio of
      myocardial endocardial flow to epicardial flow increased during an infusion of
      cilazaprilat. Both fractional shortening and lactate extraction ratio of the
      perfused area were increased (fractional shortening: 4.1 +/- 0.6% to 8.9 +/-
      0.6%, P < .001; lactate extraction ratio: -55.7 +/- 3.3% to -36.7 +/- 3.9%, P <
      .001). During an infusion of cilazaprilat, the bradykinin concentration of
      coronary venous blood was markedly increased. The increased coronary blood flow
      due to cilazaprilat was attenuated by HOE-140 (an inhibitor of bradykinin
      receptors; coronary blood flow: 35 +/- 2 mL/100 g per minute), and by N omega
      nitro-L-arginine methyl ester (an inhibitor of nitric oxide synthase; coronary
      blood flow: 34 +/- 2 mL/100 g per minute). Intracoronary administration of
      bradykinin mimicked the beneficial effects of cilazaprilat. Cyclic GMP content of
      the coronary artery was increased by cilazaprilat compared with the untreated
      condition in the ischemic myocardium. In the denervated hearts, the increased
      coronary blood flow due to cilazaprilat was not attenuated. On the other hand,
      CV11974, an inhibitor of angiotensin II receptors, slightly increased coronary
      blood flow to 34 +/- 2 from 30 +/- 1 mL/100 g per minute. CONCLUSIONS: We
      conclude that an inhibitor of ACE can increase coronary blood flow and ameliorate
      myocardial ischemia, primarily due to accumulation of bradykinin and production
      of nitric oxide from the ischemic myocardium. Inhibition of angiotensin II
      production due to inhibition of ACE partially contributes to coronary
      vasodilation in the ischemic myocardium.

PMID- 7641380
TI  - Role of thrombin compared with factor Xa in the procoagulant activity of whole
      blood clots.
AB  - BACKGROUND: Thrombi are known to induce activation of the coagulation system,
      which may be a mechanism for progression of thrombosis and its recurrence after
      thrombolysis. This study was designed to characterize the relative role of
      thrombin and activated factor X (factor Xa) as mediators of procoagulant activity
      of whole blood clots in blood and plasma. METHODS AND RESULTS: Clots formed from
      human blood were incubated in recalcified (25 mmol/L CaCl2) citrated plasma or
      nonanticoagulated blood with increasing concentrations of recombinant
      desulfatohirudin (hirudin) to inhibit thrombin activity, recombinant tick
      anticoagulant peptide (TAP) or recombinant tissue factor pathway inhibitor (TFPI)
      to inhibit factor Xa, or heparin. Fibrinopeptide A (FPA) was assayed serially as
      an index of procoagulant (thrombin) activity. FPA generation was greatly
      accelerated by addition of clots to recalcified plasma (from 1251 +/- 211 ng/mL
      after 15 minutes without clot to 5916 +/- 1412 ng/mL with clot, n = 7, P < .01)
      or whole blood (4803 +/- 761 ng/mL with clot compared with 546 +/- 233 without
      clot, n = 5, P < .05) and was attenuated by inhibitors of thrombin (> 90%
      inhibition of FPA with 0.05 mumol/L hirudin and 1.0 U/mL heparin) and factor Xa
      (> 90% inhibition of FPA with 1.0 mumol/L TAP and 0.15 mumol/L TFPI) in a
      concentration-dependent manner. Preincubation of clots with tissue-type
      plasminogen activator sufficient to induce partial clot lysis increased the rate
      of thrombin-induced FPA generation by increasing the surface area of clot exposed
      to plasma. However, procoagulant activity induced by partially lysed clots was
      attenuated by lower concentrations of both thrombin and Xa inhibitors, presumably
      because access of the inhibitors to bound procoagulant molecules was facilitated.
      Comparable results were obtained with incubations in nonanticoagulated blood.
      CONCLUSIONS: These results indicate that factor Xa is primarily responsible for
      the procoagulant activity of clots in vitro and suggest a potential molecular
      mechanism for the observed efficacy of inhibitors of factor Xa in preventing
      recurrent thrombosis after coronary thrombolysis.

PMID- 7641381
TI  - Investigation of coronary vessels in microscopic dimensions by two- and three
      dimensional NMR microscopic imaging in the isolated rat heart. Visualization of
      vasoactive effects of endothelin 1.
AB  - BACKGROUND: Nuclear magnetic resonance (NMR) imaging of macroscopic coronary
      vessels is rapidly advancing, whereas little attention has focused on development
      of NMR techniques for investigation of coronary microvessels. Such techniques
      would be of particular importance, since conventional methods to visualize
      coronary microvessels have specific limitations. The aim of our study was to
      develop two- and three-dimensional (2D and 3D) high-resolution imaging of
      coronary microvessels. Quantitative analysis of vessel size was performed in
      tomograms and applied to evaluate the vasoconstrictor effect of endothelin 1.
      METHODS AND RESULTS: Angiographic imaging was performed on an 11.75-T magnet by
      2D and 3D gradient-echo pulse sequences. In tomograms, the validity of this
      method in providing correct vessel size was tested by phantom experiments.
      Experiments were carried out in the isolated constant-pressure-perfused rat heart
      with continuous registration of coronary flow and left ventricular pressure. NMR
      pulse sequences were pressure-triggered in mid diastole. Four groups of hearts
      were studied. In group 1 (n = 20), 2D imaging perpendicular and parallel to the
      long axis of the heart was performed. Cross sections of vessels with diameter >
      140 microns were clearly detectable. In group 2 (control, n = 5) and group 3 (n =
      13), tomograms perpendicular to the long axis were obtained before and after
      administration of vehicle (group 2) and 200 pmol endothelin 1 bolus (group 3).
      Vehicle had no effect on vessel cross section. Endothelin 1, which decreased
      global coronary flow by 47%, reduced vessel cross section by 38 +/- 19%. A weak
      but, on average, significant inverse correlation between area of cross section
      and vessel size was found. In group 4 (n = 10), 3D imaging was performed in 7
      normal hearts and 3 hearts with anterior myocardial infarction. A 3D image of the
      entire coronary artery tree was obtained, revealing excellent agreement with
      anatomic studies. In infarcted rat hearts, occlusion of the left coronary artery
      was demonstrated. CONCLUSIONS: Visualization and quantification of coronary
      microvessels are feasible by NMR microscopy. NMR microscopy bears the potential
      of becoming a powerful tool for the investigation of the coronary
      microcirculation.

PMID- 7641382
TI  - Hemodynamic mechanisms responsible for reduced subendocardial coronary reserve in
      dogs with severe left ventricular hypertrophy.
AB  - BACKGROUND: Reduced subendocardial coronary reserve is a hallmark of left
      ventricular hypertrophy (LVH). The goal of this study was to determine whether
      hemodynamic, as opposed to structural, mechanisms were responsible for the
      reduced subendocardial coronary reserve. METHODS AND RESULTS: The effects of near
      maximal vasodilation with adenosine were examined in 10 conscious dogs with LVH
      (79% increase in ratio of LV weight to body weight) induced by aortic banding in
      puppies with and without preload reduction. At baseline, LV end-diastolic
      pressure, LV end-diastolic circumferential and compressive radial wall stresses,
      and LV myocardial blood flow were similar in dogs with LVH and sham-operated
      controls, while LV end-systolic circumferential wall stress tended to be greater
      in the LVH group compared with the control group. In control dogs, adenosine
      reduced LV circumferential end-systolic and end-diastolic wall stresses and
      compressive radial subendocardial wall stress; LV subendocardial blood flow
      increased (from 1.41 +/- 0.16 to 3.58 +/- 0.27 mL.min-1.g-1) and the ratio of
      subendocardial to subepicardial blood flow decrease from 1.30 +/- 0.07 to 0.69 +/
      0.05. In dogs with LVH, during adenosine infusion, LV circumferential end
      systolic and end-diastolic wall stresses and LV radial subendocardial wall
      stresses remained elevated, the increase in LV subendocardial blood flow was
      significantly smaller (from 1.11 +/- 0.11 to 2.27 +/- 0.24 mL.min-1.g-1, P <
      .05), and the subendocardial/epicardial ratio fell to a lower level (from 1.22 +/
      0.17 to 0.35 +/- 0.03, P < .05). When LV wall stresses during adenosine were
      reduced in a subgroup of 5 dogs with LVH, the endocardium/epicardium ratio during
      adenosine infusion was no longer different from that in control dogs (0.63 +/-
      0.11), nor was the level of subendocardial blood flow different (3.42 +/- 0.60
      mL.min-1.g-1). CONCLUSIONS: These data suggest that hemodynamic factors, eg,
      compressive forces, are an important component of the reduced subendocardial
      coronary reserve as opposed to structural alterations, even in the presence of
      severe LVH.

PMID- 7641383
TI  - Acute rejection accelerates graft coronary disease in transplanted rabbit hearts.
AB  - BACKGROUND: The relation between episodes of acute rejection and the development
      of graft coronary arteriosclerosis remains controversial. We examined the
      hypothesis that acute rejection episodes accelerate graft coronary
      arteriosclerosis lesion formation in rabbit allografts. METHODS AND RESULTS: A
      control group (n = 5) received cyclosporine 5 mg.kg-1.d-1 for 6 weeks after
      heterotopic heart transplantation. In a rejection group (n = 5), cyclosporine was
      omitted for 4 days at 1 and 4 weeks after transplantation. We studied cross
      sections of grafted hearts at 6 weeks and evaluated myocardial rejection grade,
      incidence, and severity and cell composition of intimal lesions in multiple
      coronary artery profiles. Episodic withdrawal of cyclosporine augmented
      myocardial rejection (International Society for Heart and Lung Transplantation
      grades 0, 0, 0, 0, and 1A in the control group to grades 1A, 1B, 2, 3A, and 3B in
      the rejection group). Episodes of acute rejection significantly increased the
      incidence (7.8 +/- 2.7% to 49.7 +/- 1.9%) and severity (from grade 0.10 +/- 0.04
      to 0.79 +/- 0.24) of intimal thickening in graft coronary arteries. Most intimal
      lesions consisted of smooth muscle cells and contained various degrees of T
      lymphocyte infiltration but sparse macrophages. CONCLUSIONS: In this experimental
      model, episodes of acute rejection precipitated by cyclosporine withdrawal
      accelerated the development of graft vascular lesion formation. Activation of
      vascular cells and leukocyte recruitment during acute rejection may thus
      contribute to the pathogenesis of graft arteriosclerosis.

PMID- 7641385
TI  - Chest pain in a patient with congenital heart disease.

PMID- 7641384
TI  - Comparison of thallium-201 resting redistribution with technetium-99m-sestamibi
      uptake and functional response to dobutamine for assessment of myocardial
      viability.
AB  - BACKGROUND: 201Tl scintigraphy is useful for determination of viability in
      patients with coronary artery disease and depressed left ventricular function.
      Whether 99mTc sestamibi is adequate for viability detection remains
      controversial. The primary goal of this study was to compare 99mTc-sestamibi
      uptake with 201Tl uptake in canine models of sustained low flow and regional
      asynergy for determination of viability. A secondary objective was to compare
      myocardial uptake of these tracers with the functional response to low-dose
      dobutamine. METHODS AND RESULTS: In protocol 1, 14 open-chested, anesthetized
      dogs with a 50% reduction in resting left anterior descending coronary artery
      (LAD) flow underwent 1 hour of transient LAD occlusion followed by reperfusion
      through the severe stenosis. Then 1.0 mCi of 201Tl was injected, and serial
      imaging was performed 5 minutes and 2 hours later. After acquisition of the
      delayed 201Tl image, 10 mCi of 99mTc sestamibi was injected, and imaging was
      repeated 45 minutes later. No significant difference was seen between the 201Tl
      defect ratio (LAD/left circumflex coronary artery [LCx]) on redistribution images
      (0.62 +/- 0.02) and 99mTc-sestamibi defect ratio (0.60 +/- 0.02). Similarly,
      LAD/LCx activity ratios by gamma-well counting were comparable (0.62 +/- 0.02
      versus 0.59 +/- 0.04) and reflected the flow decrement. Systolic thickening was 
      11 +/- 3% at the time of tracer injection. In protocol 2, 16 dogs underwent
      serial 201Tl and 99mTc-sestamibi imaging during a 50% reduction in LAD flow with
      no superimposed transient LAD occlusion. In this model, the 99mTc-sestamibi
      LAD/LCx image defect ratio (0.61 +/- 0.03) was significantly less than the 201Tl
      redistribution image defect ratio (0.66 +/- 0.03, P < .01). In 10 dogs, the
      stenosis was released, resulting in a significant increase in systolic thickening
      (P = .003), which increased further in response to 5 micrograms.kg-1.min-1 of
      dobutamine (P = .02). In contrast, thickening increased only from -7 +/- 3% to 2
      +/- 4% (P = .004) in response to dobutamine infusion in the remaining 6 dogs with
      persistent severe LAD stenoses. In protocol 3, 5 dogs received both 201Tl and
      99mTc sestamibi to compare the degree of delayed redistribution between tracers
      at 2 hours. The LAD/LCx microsphere flow ratios when 201Tl and 99mTc sestamibi
      were injected were 0.44 +/- 0.06 and 0.43 +/- 0.05 (P = NS), respectively. The
      LAD/LCx activity ratio by gamma-well counting was greater for 201Tl (0.56 +/-
      0.08) than 99mTc sestamibi (0.50 +/- 0.07) at 2 hours of redistribution (P <
      .05), indicating greater redistribution for 201Tl. The LAD/LCx 99mTc-sestamibi
      defect ratios on serial imaging improved from 0.49 +/- 0.07 to 0.52 +/- 0.07 (P =
      .0005), consistent with a slight amount of 99mTc-sestamibi redistribution. In
      protocol 4, no difference between 201Tl and 99mTc-sestamibi defect magnitudes was
      seen in 4 dogs undergoing 3 hours of total LAD occlusion and ligation of visible
      coronary collaterals. Infarct size was 68 +/- 19% of the risk area. CONCLUSIONS:
      Although 99mTc-sestamibi and 201Tl defect magnitudes and regional activities were
      comparable in dogs with sustained low coronary flows and superimposed
      subendocardial infarctions and in dogs with large infarctions, approximately 5%
      more 201Tl than 99mTc-sestamibi uptake was observed in dogs with chronic low flow
      and severe systolic dysfunction. Substantial 99mTc-sestamibi uptake in asynergic
      zones was observed in this low-flow model, with some slight resting 99mTc
      sestamibi redistribution observed on serial images. Systolic thickening was
      negligibly enhanced during dobutamine infusion in dogs with sustained low flow,
      whereas 201Tl uptake was only mildly reduced.

PMID- 7641386
TI  - Managing acetaminophen overdose.

PMID- 7641387
TI  - Identifying early markers of type II diabetes.

PMID- 7641388
TI  - Dopamine agonists in the treatment of Parkinson's disease.
AB  - Bromocriptine or pergolide can be used as initial monotherapy in Parkinson's
      disease. When used as an adjuvant to levodopa therapy, these drugs can result in
      clinical improvement and a decreased levodopa requirement. To avoid side effects,
      the starting dosage should be low (1.25 mg per day of bromocriptine or 0.05 mg of
      pergolide) and should be increased slowly. The standard daily dose of
      bromocriptine ranges from 7.5 to 60 mg, and of pergolide, from 0.75 to 4 mg.
      Combination therapy with low dosages of levodopa and a dopamine agonist may also
      decrease the incidence of side effects of both agents.

PMID- 7641389
TI  - Oral disease in the geriatric patient: the physician's role.
AB  - In the elderly, oral health has a profound impact on general well-being. The
      ability to quickly identify potentially harmful oral health problems is valuable
      to the physician, who generally will see an older patient more often than the
      dentist will.

PMID- 7641390
TI  - Current status of stress echocardiography in the diagnosis of coronary artery
      disease.
AB  - Stress echocardiography is a cost-effective and reliable diagnostic test for
      patients with suspected coronary artery disease. Stress echocardiography should
      be used in preference to exercise electrocardiography as the primary test in
      patients with uninterpretable ST segments. It is attractive for use as the
      primary test in patients with coexisting valvular disease. It probably is the
      optimal test for women. Stress echocardiography should be used as a secondary
      test when the result of exercise electrocardiography is inconsistent with the
      clinical status. In patients requiring nonexercise stress testing, an imaging
      test is mandatory. The ability of stress echocardiography to identify the
      location and extent of myocardial ischemia makes it appropriate in situations
      where decisions regarding revascularization will be made on these grounds. The
      overall accuracy of stress echocardiography and perfusion scintigraphy is
      comparable in expert hands. but one must always consider the expertise of the
      operator and the quality of each test in the environment in which it is
      performed.

PMID- 7641391
TI  - Stress echocardiography: its emerging role in identifying viable myocardium.

PMID- 7641392
TI  - Pathogenesis of epilepsy: the role of excitatory amino acids.
AB  - EAAs appear to have a major role in both the development and the propagation of
      seizures. However, since EAAs have an important role in learning and brain
      plasticity, it is important that future investigators study not only the
      antiepileptic and neuroprotective properties of EAA antagonists, but also their
      effects on learning, memory, and behavior.

PMID- 7641393
TI  - Drugs for the prevention and treatment of acute renal failure.
AB  - Certain preventive measures might decrease the incidence or severity of acute
      renal failure, including vigorous hydration before the administration of
      radiocontrast agents, and use of mannitol, loop diuretics, dopamine, and calcium
      antagonists. However, the pharmacologic agents should be used judiciously, and
      clinicians should not accept blindly that they are indicated in all clinical
      situations involving acute renal failure until further studies are available.

PMID- 7641394
TI  - Trends in radiation oncology: a review for the nononcologist.
AB  - Fifty percent of cancer patients will undergo radiation therapy for either cure
      or palliation. This paper reviews the basic principles, practice, and future
      trends.

PMID- 7641395
TI  - Caring for dying patients: physicians and assisted suicide.

PMID- 7641396
TI  - Postpartum myocardial infarction: association with primary coronary artery
      dissection.
AB  - CASE SUMMARY: A 36-year-old woman presented with an acute myocardial infarction 2
      weeks after the birth of her first child. The patient had smoked two packs of
      cigarettes a day for 12 years and had been taking bromocriptine to suppress
      lactation. While in the emergency room, the patient went into ventricular
      fibrillation, but defibrillation successfully restored sinus rhythm. Coronary
      angiography revealed several atherosclerotic lesions. The patient refused to
      undergo coronary artery bypass grafting, and she was discharged receiving medical
      therapy. DISCUSSION: Forty-eight cases of postpartum myocardial infarction have
      previously been reported; the present case makes 49. In 41 cases a cardiac
      examination was performed, either on necroscopy or by angiography. Twenty-two
      (54%) of the 41 patients had occlusion related to primary coronary artery
      dissection, 11 (27%) had normal coronary arteries and presumed spasm, and only 6
      (15%) had atherosclerosis-related coronary occlusion. The mortality rate was 39%,
      and surviving patients had significant cardiac limitation. CONCLUSION: Postpartum
      myocardial infarction and coronary occlusion, when they do occur, are frequently
      caused by primary coronary artery dissection. Immediate recognition of this
      association may significantly reduce morbidity and mortality for these patients.

PMID- 7641397
TI  - Impact of the health care marketplace on tertiary care institutions.

PMID- 7641398
TI  - Clinical practice guidelines: non-Hodgkin's lymphomas.
AB  - BACKGROUND: Despite the common clonal origin of the non-Hodgkin's lymphomas
      (NHLs), their characteristic diversity contributes to the difficulty of defining
      comprehensive treatment regimens. OBJECTIVES: To review and compare historical
      and current data that define practice guidelines in the treatment of the NHLs.
      DISCUSSION: Early-stage, low-grade NHLs: Irradiation remains the standard
      treatment. Late-stage, low-grade NHLs and advanced-stage indolent lymphomas:
      Alkylating agents (eg, chlorambucil, cyclophosphamide) are the standard response,
      although recent studies suggest maintaining a vigilant, watch-and-wait course
      anticipatory of intervention. Some new therapies, alone or in combination, offer
      potential for development (eg, the chemotherapeutic agents fludarabine, 2'
      deoxycoformycin, and 2-chlorodeoxyadenosine for low-grade NHLs, and bone marrow
      transplantation, monoclonal antibodies, and recombinant interferon-alfa for
      advanced-stage indolent lymphomas). Intermediate-grade aggressive and high-grade
      NHLs: Combination chemotherapy (ie, CHOP) is the historical treatment, plus
      regional irradiation, with CNS prophylaxis an additional option in high-grade
      lymphoblastic disease, and bone marrow transplantation an additional option in
      large-cell immunoblastic and small noncleaved-cell NHLs. CONCLUSIONS: Presently
      accepted therapies remain the mainstays in treating the NHLs; however,
      progressive therapeutic regimens, such as watching and waiting for intermediate
      level disease progression or employing salvage, high-dose chemotherapeutic
      regimens, often with bone marrow transplantation, in intermediate- or high-grade
      disease stages, have yielded measurable successes in significant minorities of
      patients.

PMID- 7641399
TI  - Large goitre as a maladaptation to iodine deficiency.

PMID- 7641400
TI  - Investigation of delayed puberty.
AB  - Delayed puberty is defined arbitrarily on the basis of statistical consideration,
      when no signs of puberty have occurred at 2.0 SD (13.4 years in girls and 13.8 in
      boys) above the mean chronological age for the onset of puberty. The vast
      majority of these patients have no endocrine abnormality and their pubertal
      development and growth spurt are simply consequences of primary delay
      (constitutional delay of growth and puberty (CDGP)) or secondary delay due to a
      chronic disease of childhood, such as asthma. However, a small proportion may
      have pathological causes of delayed puberty which must be careful identified as
      specific management may be required. Associated with delayed puberty, the growth
      spurt is always delayed which is why the condition is described as delayed growth
      and puberty. Short stature and lack of sexual development may lead to emotional
      and social difficulties and in some patients their consequences can persist when
      'normal' height and full sexual maturation are attained. Recent data also suggest
      that a delay in the 'tempo' of pubertal maturation may interfere with the normal
      bone accretion occurring during puberty, later causing osteoporosis. Such
      findings suggest that a new approach in delayed puberty may be necessary not only
      for psychological reasons but also for optimizing bone mass accretion.

PMID- 7641401
TI  - The effects of high altitude on hypothalamic-pituitary secretory dynamics in men.
AB  - OBJECTIVE: Individuals adapted to high altitude (HA) have abnormalities in
      endocrine function and specifically in the pituitary-thyroid axis and aldosterone
      regulation. In this study we assessed hypothalamic-pituitary function in men
      adapted to high altitude living using exogenous administration of synthetic
      hypothalamic hormones. DESIGN: Growth hormone releasing hormone (Geref 1-29) 1
      microgram/kg, TRH 500 micrograms, GHRH 100 micrograms and ovine corticotrophin
      releasing hormone (oCRH) 1 microgram/kg were simultaneously administered
      intravenously to two groups of men: 12 born and raised in the city of Pasto,
      Colombia, South America, located at an altitude of 2600 m in the southern
      Colombian Andes (HA group) and 10 men living at sea level (SL) in Tampa, Florida.
      MEASUREMENTS: The following hormones were measured: GH, IGF-I, TSH, T4, free T4,
      free T3, PRL, ACTH, beta-endorphin and cortisol. IGF binding protein-3 (IGFBP-3)
      and cortisol binding globulin (CBG) were also measured. RESULTS: GH response to
      GHRH in HA men was exaggerated compared to SL men, and IGF-I concentration was
      also significantly increased in the presence of normal levels of IGFBP-3. No
      differences in TSH or PRL responses were found following TRH. HA men had lower
      basal total T4 levels, but higher free T4 and free T3 concentrations. The basal
      ACTH concentrations in the HA men were significantly lower than SL, although the
      response to oCRH was still present. beta-Endorphin basal levels were similar at
      HA and SL but the response to oCRH at HA was blunted. At HA, basal cortisol
      levels as well as CBG were elevated compared to SL and, in contrast to SL, did
      not increase significantly after endogenous ACTH secretion. CONCLUSIONS: This
      study is the first description of exaggerated GH response to the administration
      of GHRH in HA men and also of a significant increase in IGF-I concentration in
      the same subjects in the presence of normal levels of IGFBP-3. An altered
      hypothalamic-pituitary response was found in HA men after administration of oCRH
      characterized by a significantly lower basal ACTH concentration at HA, although
      the response to oCRH was present but the beta-endorphin response to oCRH was
      blunted. At HA, basal cortisol levels, as well as CBG, were elevated and the
      cortisol levels did not significantly increase after endogenous ACTH secretion.
      We have characterized the differences in hypothalamic-pituitary dynamics after
      the administration of TRH, GnRH and oCRH in HA men comparing their response to
      age/sex matched SL men.

PMID- 7641402
TI  - Bioactive GH-like immunoglobulins G in active acromegaly: response to long-term
      treatment with bromocriptine.
AB  - In acromegaly, certain forms of circulating immunoreactive hGH are not true GH
      but IgGs which possess GH biological activity (bioactive GH-like IgGs). In this
      study, we tested the effect of bromocriptine on circulating bioactive GH-like
      IgGs in an acromegalic woman. Increasing doses of oral bromocriptine (2.5, 5.0
      and 7.5 mg/day) were administered (for 2, 8 and 6 months respectively). TRH tests
      were performed before treatment and at the end of treatment with each dose. The
      patient was without detectable pituitary or extra-pituitary tumour by magnetic
      resonance imaging. Her serum contained bioactive GH-like IgGs equivalent to 240
      mU/l of hGH and elevated insulin-like growth factor I (IGF-I; 9500 U/l). Basal
      hGH was 12.8 mU/l and increased to 220 mU/l 15 min after TRH (200 micrograms,
      i.v.). In addition, in the basal samples of each test we measured total IgGs
      (radial immunodiffusion), bioactive GH-like IgGs (isolated by Sephadex and
      protein A affinity chromatography and assayed using the Nb2 cell assay) and IGF
      I(RIA). Bromocriptine treatment gradually reduced serum levels of bioactive GH
      like IgGs and IGF-I, with significant falls observed first at 10 months of
      treatment. Bioactive GH-like IgGs were 240, 240, 36.0 and < 0.124 mU/l and IGF-I
      levels were 9500, 8700, 4000 and 3100 U/l at 0, 2, 10 and 16 months of treatment,
      respectively. In contrast, IR-hGH response to TRH decreased after 2 months of
      treatment to 89 mU/l and to 49.2 mU/l at the end of the study while basal IR-hGH
      remained between 13 and 8.4 mU/l. Basal PRL fell to almost undetectable levels.
      Bromocriptine treatment decreased the GH response to TRH and the serum
      concentration of bioactive GH-like IgGs and IGF-I. The striking similarity
      between the pattern of decrease of serum bioactive GH-like IgGs and IGF-I
      supports the presence of an immuno component in our patient's acromegaly.

PMID- 7641403
TI  - Octreotide exacerbated fasting hypoglycaemia in a patient with a proinsulinoma;
      the glucostatic importance of pancreatic glucagon.
AB  - Octreotide, a long-acting somatostatin analogue, has been used to alleviate
      hypoglycaemia in patients with insulinomas. Transient worsening of fasting
      hypoglycaemia following octreotide has also been described (Stehouwer et al.,
      1989). We describe a patient with a 'proinsulinoma' in whom octreotide caused
      rapid and prolonged symptomatic worsening of fasting hypoglycaemia. Catecholamine
      and cortisol counterregulatory hormonal responses were normal but those of
      glucagon and GH were impaired. Acute neuroglycopaenic symptoms were present
      during octreotide induced hypoglycaemia, which was accompanied by and attributed
      to an acute reduction in pancreatic glucagon secretion in the presence of
      persistent and unsuppressed hyperproinsulinaemia. This suggests that glucagon may
      be important in maintaining glucose homeostasis in chronic hypoglycaemia due to
      endogenous hyperinsulinism even though its concentration in the peripheral blood
      is not raised.

PMID- 7641404
TI  - Low frequency of germline mutations in the RET proto-oncogene in patients with
      apparently sporadic medullary thyroid carcinoma.
AB  - BACKGROUND AND OBJECTIVES: Medullary thyroid carcinoma (MTC) occurs both
      sporadically and in the autosomal dominantly inherited multiple endocrine
      neoplasia (MEN) type 2 syndromes. The distinction between true sporadic MTC and a
      new mutation familial case is important for future clinical management of both
      the patient and family. The susceptibility gene for MEN 2 is the RET proto
      oncogene. Systematic analysis for germline mutations of the RET proto-oncogene
      was performed in a series of 67 patients with apparently sporadic MTC to
      determine whether they were true sporadic cases or unsuspected de novo MEN 2
      cases. DESIGN AND PATIENTS: Sixty-seven unselected patients with sporadic MTC
      were randomly ascertained from clinic patients from four centres. The diagnosis
      of MTC was confirmed by histopathology. Germline DNA was extracted from
      peripheral blood leucocytes or from paraffin-embedded tissue and subsequently
      used for polymerase chain reaction amplification. MEASUREMENTS: Polymerase chain
      reaction based RET mutation analysis was performed by direct double-stranded
      cycle sequencing of exons 10, 11, 13 and 16, within which the majority of MEN2
      mutations have been shown to occur. RESULTS: In this series, there was one proven
      case of germline mutation in RET codon 620, which previously has been shown to be
      responsible for MEN 2, thus indicating heritable disease. No germline mutation in
      codon 918, typical of MEN 2B, was found. CONCLUSIONS: A figure of 1.5% germline
      mutations in 67 apparently sporadic MTC is lower than the incidence of familial
      disease reported in previous series involving clinical and biochemical screening.
      The presence of a germline mutation in the RET proto-oncogene in a patient with
      MTC indicates heritable disease. The absence of germline RET exon 10, 11, 13 or
      16 mutation appears to rule out MEN 2A to a high probability, although the
      presence of a familial form of MTC other than classical MEN 2A cannot be excluded
      conclusively.

PMID- 7641405
TI  - Appearance of Graves'-like disease after radioiodine therapy for toxic as well as
      non-toxic multinodular goitre.

PMID- 7641406
TI  - Primary hyperparathyroidism and vitamin D deficiency.

PMID- 7641407
TI  - Addison's disease.

PMID- 7641408
TI  - Investigation, management and therapeutic outcome in 12 cases of childhood and
      adolescent Cushing's syndrome.
AB  - OBJECTIVE: Cushing's syndrome in childhood and adolescence is rare. We analysed
      the clinical presentation, investigation, management and therapeutic outcome in
      12 paediatric patients with Cushing's syndrome. DESIGN: Retrospective review of
      case notes. PATIENTS: Twelve patients, 7 males and 5 females, aged 7.6-17.8 years
      with Cushing's syndrome who were admitted to St Bartholomew's Hospital between
      1978 and 1993, were studied. Aetiologies of the Cushing's syndrome patients were:
      Cushing's disease (9), adrenal adenoma (1), nodular adrenocortical dysplasia (1)
      and ectopic ACTH syndrome (1). One further male patient, aged 17.8 years who
      presented with Nelson's syndrome after bilateral adrenalectomy for Cushing's
      disease in 1978, is described. MEASUREMENTS: Presenting symptoms, endocrine tests
      for hypercortisolism, imaging studies, simultaneous bilateral inferior petrosal
      sinus sampling and therapeutic strategies are discussed. RESULTS: The dominant
      clinical features were obesity, short stature, virilization, headaches, fatigue
      and emotional lability. Investigations confirmed Cushing's syndrome by
      demonstrating absent cortisol circadian rhythm and impaired suppression on low
      dose dexamethasone test and differentiated Cushing's disease from other
      aetiologies by high dose dexamethasone and hCRH tests. In Cushing's disease,
      pituitary CT scan identified a microadenoma in 4 out of 9 subjects. In 5 of the 9
      patients (3 with a normal pituitary CT, 2 with a suggested microadenoma), a
      pituitary MRI scan was performed and confirmed the CT findings. Inferior petrosal
      sinus catheterization for ACTH in 4 patients confirmed excess pituitary ACTH
      secretion, correctly lateralizing the tumour in all cases. Cushing's disease was
      treated by transsphenoidal surgery alone in 6 patients and combined with
      pituitary irradiation in 3 patients. Of these 9 patients, 7 are cured and 2 are
      in remission. The patient with Nelson's syndrome is cured after total
      hypophysectomy. CONCLUSIONS: This series describes the clinical features,
      aetiologies and management of juvenile Cushing's syndrome. Investigation with low
      and high-dose dexamethasone suppression tests and hCRH test identified the
      aetiology in each case. Collaboration between paediatric and adult endocrine
      units together with an experienced neurosurgeon and a radiotherapist contributed
      to the successful therapeutic outcome of these patients.

PMID- 7641409
TI  - Benzodiazepines attenuate the pituitary-adrenal responses to corticotrophin
      releasing hormone in healthy volunteers, but not in patients with Cushing's
      syndrome.
AB  - OBJECTIVE: The corticotrophin-releasing hormone (CRH) stimulation test has become
      established as a powerful tool in differentiating the source of ACTH in patients
      with Cushing's syndrome. Psychiatric symptoms are common in patients with
      Cushing's syndrome, and many patients with psychiatric illnesses may show
      disturbances of function of the pituitary-adrenal axis; both of these groups of
      patients may be receiving benzodiazepine drugs when presenting for evaluation of
      their possible endocrine problems. Both animal and human studies suggest that
      interactions occur between benzodiazepines and the hypothalamo-pituitary-adrenal
      axis. We have therefore evaluated the effects of a benzodiazepine drug on the
      pituitary-adrenal response to CRH. DESIGN: We have investigated the effects of 20
      mg oral temazepam or placebo on serum cortisol and plasma ACTH after the
      administration of 100 micrograms i.v. human CRH in 12 healthy volunteers and in 9
      patients with Cushing's syndrome. RESULTS: Temazepam significantly inhibited the
      peak serum/plasma levels and area under the curve for circulating cortisol and
      ACTH in normal subjects after CRH, but there was no such difference after
      temazepam in patients with Cushing's syndrome. CONCLUSIONS: Our results have
      shown that temazepam inhibits the pituitary-adrenal responses to human CRH in
      normal subjects, but not in those with Cushing's syndrome. We believe that
      inhibition of endogenous AVP by temazepam is the most likely explanation for our
      findings in healthy volunteers: the hypercortisolaemia in Cushing's syndrome
      suppresses the release of both endogenous CRH and AVP in portal blood which then
      results in abolition of the temazepam induced reduction in the pituitary-adrenal
      response to exogenous CRH, as seen in our patients. These effects of
      benzodiazepines should clearly be taken into account in patients using these
      compounds while undergoing endocrine assessment.

PMID- 7641410
TI  - Oestrogen formation from androstenedione in human bone.
AB  - BACKGROUND AND OBJECTIVE: Peripheral aromatization of testosterone and
      androstenedione is the principal source for circulating oestrogens in men and in
      castrated and post-menopausal women. Since human bone is a target organ for
      androgens and oestrogens, aromatase activity was assessed in human spongiosa
      obtained from patients who were undergoing orthopaedic surgery. DESIGN AND
      PATIENTS: In initial experiments for assessing aromatization, oestrogen formation
      from 1,2,6,7-3H-androstenedione was compared with the release of tritiated water
      from 1 beta-3H-androstenedione. Since the rates of enzyme activity were similar
      with the two methods, rates of oestrogen formation were determined under
      standardized conditions with the tritiated water generation technique in bone
      specimens obtained from 4 men and 11 post-menopausal women. RESULTS: The apparent
      Km of the aromatase ranged between 6 and 50 nM (20.4 +/- 3.9; mean +/- SEM),
      values in the range of those reported for human placental microsomes. The maximum
      velocity (Vmax) of the aromatase activity ranged between 0.14 and 1.23 nmol/g
      DNA/h. CONCLUSIONS: Oestrogens formed in human bone may play a physiological role
      in steroid hormone action in this tissue.

PMID- 7641411
TI  - Effects of quinagolide (CV 205-502), a selective D2-agonist, on vascular
      reactivity in patients with a prolactin-secreting adenoma.
AB  - BACKGROUND: Quinagolide (CV 205 502) is a dopamine D2-receptor agonist which has
      proved effective in the treatment of prolactinomas, reducing both serum PRL and
      tumour size. Some of its D2-receptor effects are mediated via alpha
      adrenoceptors, which have a major influence on the control of vascular tone. The
      aim of this study was to examine the influence of quinagolide on in-vivo dorsal
      hand vein vascular responses to noradrenaline in patients with a prolactinoma.
      DESIGN AND PATIENTS: Seven female patients with prolactinomas (age 37 (28-46)
      years), intolerant of bromocriptine, were studied before and after 3 months
      treatment with quinagolide (0.75-1.5 mg/day). Patients were otherwise disease
      free, were taking no other medication, and had been on no other medication
      (including bromocriptine) for at least 3 months prior to enrollment into the
      study. MEASUREMENTS: Vascular responses to locally infused noradrenaline were
      measured in dorsal hand veins using an established technique. PRL, oestradiol,
      FSH, LH, blood pressure and body mass index were also measured before and after 3
      months treatment. RESULTS: Quinagolide significantly reduced PRL in all 7
      patients (1795 (696-4680) (mean (range)) vs 488 (290-868) mU/l, P = 0.001), with
      no effect on the other parameters, including mean arterial pressure (88 (2) vs 87
      (4) mmHg, P = 0.6). Vascular reactivity to noradrenaline was significantly
      increased after 3 months therapy: log10 dose estimated to cause 50%
      vasoconstriction (ED50) 1.37 (0.12) vs 0.85 (0.12) ng/min (P = 0.003; a lower
      ED50 indicates less noradrenaline is required to constrict the vein by 50%).
      CONCLUSIONS: Vasoconstrictor responses to noradrenaline were increased in all
      patients after 3 months treatment with quinagolide. Peripheral veins carry alpha
      adrenoceptors analogous to those of systemic resistance vessels. If this
      increased vasoconstrictor response in patients with prolactinomas was occurring
      in hypophyseal vessels, it would lead to reduced tumour blood supply. Quinagolide
      may therefore reduce tumour blood flow, which may be one factor responsible for
      its effectiveness in these patients.

PMID- 7641413
TI  - Genetic counselling in complete androgen insensitivity syndrome: trinucleotide
      repeat polymorphisms, single-strand conformation polymorphism and direct
      detection of two novel mutations in the androgen receptor gene.
AB  - OBJECTIVE: Androgen insensitivity syndrome is a disorder of male sexual
      development which results in varying degrees of undervirilization in 46XY
      individuals with functional testes. In the most severe form, complete androgen
      insensitivity syndrome (CAIS), patients have a normal female appearance. Although
      CAIS is not life-threatening, affected individuals are infertile and require
      counselling, gonadectomy, hormone therapy, and sometimes vaginoplasty. Many
      families therefore request genetic counselling. Defects in the androgen receptor
      gene account for most if not all cases of CAIS. The purpose of this study was to
      evaluate the use of the polyglutamine and polyglycine trinucleotide repeat
      polymorphisms in the first exon of the androgen receptor gene for carrier status
      determination in three CAIS families. In two of these families novel mutations in
      the androgen receptor gene were subsequently identified which allowed
      confirmation of carrier status and also a prenatal diagnosis to be made in one
      family. PATIENTS: Three CAIS families were studied. The index cases all presented
      with a clinical phenotype typical of CAIS. MEASUREMENTS: Family members were
      typed initially for the polyglutamine repeat. In one family this was not
      informative and the polyglycine repeat was therefore studied. In this and one
      further family, the androgen receptor gene was sequenced to identify the mutation
      causing the CAIS. RESULTS: On the basis of information from trinucleotide repeat
      analysis carrier status could be assessed in each family. In one family, evidence
      for somatic instability of the polyglutamine repeat was found. In the same
      family, a novel mutation in the androgen receptor gene, which substituted valine
      for leucine 881, was identified. Other family members were subsequently typed for
      the mutation and a prenatal diagnosis was performed. A novel mutation was also
      identified in a second family substituting the glycine codon at position 371 with
      a stop codon. Other family members were typed for this mutation. CONCLUSIONS:
      Both the polyglutamine and polyglycine repeat polymorphisms are useful for the
      genetic counselling of complete androgen insensitivity syndrome families. In some
      cases, however, where the family history is limited, more precise information can
      be provided only once the androgen receptor mutation causing the complete
      androgen insensitivity syndrome has been identified.

PMID- 7641412
TI  - The incidence of thyroid disorders in the community: a twenty-year follow-up of
      the Whickham Survey.
AB  - BACKGROUND AND OBJECTIVE: The original Whickham Survey documented the prevalence
      of thyroid disorders in a randomly selected sample of 2779 adults which matched
      the population of Great Britain in age, sex and social class. The aim of the
      twenty-year follow-up survey was to determine the incidence and natural history
      of thyroid disease in this cohort. DESIGN, PATIENTS AND MEASUREMENTS: Subjects
      were traced at follow-up via the Electoral Register, General Practice registers,
      Gateshead Family Health Services Authority register and Office of Population
      Censuses and Surveys. Eight hundred and twenty-five subjects (30% of the sample)
      had died and, in addition to death certificates, two-thirds had information from
      either hospital/General Practitioner notes or post-mortem reports to document
      morbidity prior to death. Of the 1877 known survivors, 96% participated in the
      follow-up study and 91% were tested for clinical, biochemical and immunological
      evidence of thyroid dysfunction. RESULTS: Outcomes in terms of morbidity and
      mortality were determined for over 97% of the original sample. The mean incidence
      (with 95% confidence intervals) of spontaneous hypothyroidism in women was
      3.5/1000 survivors/year (2.8-4.5) rising to 4.1/1000 survivors/year (3.3-5.0) for
      all causes of hypothyroidism and in men was 0.6/1000 survivors/year (0.3-1.2).
      The mean incidence of hyperthyroidism in women was 0.8/1000 survivors/year (0.5
      1.4) and was negligible in men. Similar incidence rates were calculated for the
      deceased subjects. An estimate of the probability of the development of
      hypothyroidism and hyperthyroidism at a particular time, i.e. the hazard rate,
      showed an increase with age in hypothyroidism but no age relation in
      hyperthyroidism. The frequency of goitre decreased with age with 10% of women and
      2% of men having a goitre at follow-up, as compared to 23% and 5% in the same
      subjects respectively at the first survey. The presence of a goitre at either
      survey was not associated with any clinical or biochemical evidence of thyroid
      dysfunction. In women, an association was found between the development of a
      goitre and thyroid-antibody status at follow-up, but not initially. The risk of
      having developed hypothyroidism at follow-up was examined with respect to risk
      factors identified at first survey. The odds ratios (with 95% confidence
      intervals) of developing hypothyroidism with (a) raised serum TSH alone were 8 (3
      20) for women and 44 (19-104) for men; (b) positive anti-thyroid antibodies alone
      were 8 (5-15) for women and 25 (10-63) for men; (c) both raised serum TSH and
      positive anti-thyroid antibodies were 38 (22-65) for women and 173 (81-370) for
      men. A logit model indicated that increasing values of serum TSH above 2mU/l at
      first survey increased the probability of developing hypothyroidism which was
      further increased in the presence of anti-thyroid antibodies. Neither a positive
      family history of any form of thyroid disease nor parity of women at first survey
      was associated with increased risk of developing hypothyroidism. Fasting
      cholesterol and triglyceride levels at first survey when corrected for age showed
      no association with the development of hypothyroidism in women. CONCLUSIONS: This
      historical cohort study has provided incidence data for thyroid disease over a
      twenty-year period for a representative cross-sectional sample of the population,
      and has allowed the determination of the importance of prognostic risk factors
      for thyroid disease identified twenty years earlier.

PMID- 7641414
TI  - DNA synthesis by pituitary tumours, with reference to plasma hormone levels and
      to effects of bromocriptine.
AB  - BACKGROUND AND OBJECTIVE: In parathyroid adenomas and experimentally in the
      normal rat pituitary gland, cell replication and secretory activity were
      previously shown to be correlated. A similar relationship has now been
      investigated in human pituitary tumours, since this could have relevance to their
      growth and aetiology. The effect of bromocriptine on the two variables was
      examined. PATIENTS: Data were derived from 50 patients undergoing operation for
      pituitary tumour, including 15 with acromegaly and 11 with prolactinoma.
      MEASUREMENTS: Preoperative plasma levels of GH, PRL and gonadotrophins were
      measured by radioimmunoassay. DNA synthesis, an index of cell replication, was
      measured in vitro in freshly removed tumour tissue. Nuclear diameter of tumour
      cells was measured in histological sections and immunostaining for relevant
      hormones was carried out on tumour tissue. RESULTS: DNA synthesis was correlated
      (P < 0.05) with plasma hormone levels in cases of prolactinoma, both treated and
      not treated with bromocriptine, and in a group of putative FSH secreting tumours
      from male patients. The correlation was not significant in cases of acromegaly.
      Comparisons of mean values between groups treated and not treated with
      bromocriptine showed significantly lower DNA synthesis and mean nuclear diameter
      in prolactinomas under treatment but not in GH secreting tumours. CONCLUSIONS:
      The findings in prolactinomas suggest a close relationship between secretion and
      tumour cell replication dependent on still undefined agents, but including
      dopamine, affecting both variables, and isoforms of PRL, which may stimulate or
      inhibit replication of PRL secreting cells. The basis of the relationship in FSH
      secreting tumours is unknown. The relationship was absent in the non-homogeneous
      group of GH secreting tumours. When secretion and growth are correlated, the
      secretory process may be the site of the primary abnormality in the tumour cell.
      Evidence that bromocriptine inhibits tumour cell replication was obtained for
      prolactinomas but not for GH secreting tumours.

PMID- 7641415
TI  - High dose testosterone therapy for reduction of final height in constitutionally
      tall boys: does it influence testicular function in adulthood?
AB  - OBJECTIVE: We have studied the effect of treatment with high doses of androgens
      during puberty on testicular function in adult men with constitutionally tall
      stature, taking into account confounding factors interfering with sperm quality,
      since existing published data do not include whether testicular function is
      impaired by such treatment. DESIGN: Historical cohort study. PATIENTS: Forty
      three previously androgen treated tall men (cases) and 30 non-treated tall men
      (controls). MEASUREMENTS: Physical examination, semen analysis and plasma levels
      of LH, FSH, testosterone (T), sex hormone binding globulin (SHBG) and inhibin.
      RESULTS: Sperm quality and testis volume were comparable between cases and
      controls. Mean sperm concentration was 66.4 x 10(6)/ml in cases and 66.2 x
      10(6)/ml in controls. A left-sided varicocele was found in 45% of the cases and
      37% of the controls. In cases we observed a significant effect of the age at
      start of androgen therapy on sperm motility (regr. coeff. (SE): 4.92 (2.41)%, P =
      0.048). In addition, testicular size at start of therapy had a significant effect
      on sperm concentration (regr. coeff. (SE): 5.57 (1.54) x 10(6)/ml, P = 0.0012)
      and on total sperm count (regr. coeff. (SE): 43.1 (7.73) x 10(6), P = 0.0001).
      Plasma levels of T, SHBG and inhibin were not statistically different between the
      groups. Cases had significantly higher FSH levels (mean (SD) 3.3 (2.2) vs 2.1
      (0.8) IU/I, P = 0.004) and significantly lower LH levels (mean (SD) 2.3 (0.9) vs
      3.1 (1.4) IU/I, P = 0.019). We found a significant effect of age at start of
      therapy on plasma FSH level in the treated men (regr. coeff. (SE): -0.73 (0.18)
      IU/I, P = 0.0003). CONCLUSIONS: Treatment with high doses of androgens for
      reduction of final height in constitutionally tall stature has no long-term side
      effect on sperm quality, testicular volume or plasma testosterone levels.
      However, treated men had significantly higher plasma levels of FSH compared with
      controls. The meaning of this difference remains to be established. Varicocele
      was present in 42% of the adult tall men.

PMID- 7641416
TI  - The evolution of radiation-induced growth hormone deficiency in adults is
      determined by the baseline growth hormone status.
AB  - OBJECTIVE: Recent studies of GH replacement have suggested several beneficial
      effects for GH deficient adults. It would therefore be helpful to predict the
      time of onset of GH deficiency after external pituitary irradiation. We have
      studied the evolution of GH deficiency with time in patients irradiated for
      pituitary adenomas and other hypothalamic pituitary tumours. DESIGN: Analysis of
      serial peak GH responses to insulin hypoglycaemia following external irradiation
      to the hypothalamic-pituitary axis using statistical models which allowed for
      age, sex, previous surgery and the pre-radiotherapy GH peak response. PATIENTS:
      Eighty-five non-acromegalic adults (48 male), 75 of whom had either a pituitary
      adenoma or a craniopharyngioma and 10 who had other tumours in the hypothalamic
      pituitary region. All the patients had received a radiation dose between 37.5 and
      45 Gy divided into 15 fractions given over 21 days. MEASUREMENTS: The GH
      responses to an insulin tolerance test (ITT) performed as part of the regular
      endocrine follow-up in patients who received irradiation to the hypothalamic
      pituitary region. RESULTS: Three hundred and forty-five ITTs were performed over
      a period of 10 years following radiotherapy. There was a decline in the modelled
      mean peak GH response to an ITT over the first 5 years which then appeared to
      plateau. Using an extended model, women had higher GH peak responses than men and
      this difference was maintained throughout the ten-year period. The magnitude of
      the post-radiotherapy peak GH response at any given time was dependent on the
      baseline peak GH response, but the rate of the decrease was not affected (P =
      0.66). To develop severe GH deficiency (peak GH response less than 5 mU/l) after
      radiotherapy it took patients with baseline GH peaks of 30, 20 and 10 mU/l
      approximately 4 years, 3 years and 1 year respectively. Those patients with a
      baseline GH peak of greater than 50 mU/l are unlikely to develop severe GH
      deficiency within the first 5 years following radiotherapy. CONCLUSION: These
      results provide an insight into the pattern of the decline in GH secretion
      following radiotherapy in patients with pituitary disease and the factors
      affecting it. This information will help the clinician predict the frequency and
      timing of GH deficiency in patients irradiated for pituitary disease and the
      potential need for GH replacement therapy.

PMID- 7641417
TI  - Developmental progression of Gpd expression from the inactive X chromosome of the
      Virginia opossum.
AB  - Metatherian (marsupial) mammals possess a non-random form of X-chromosome
      inactivation in which the paternally-derived X is always the one inactivated. To
      examine the progression of X-linked gene expression during metatherian
      development, we compared relative levels of the maternally and paternally encoded
      Gpd gene products in heterozygous female Virginia opossums (Didelphis virginiana)
      across a major portion of the developmental period. Panels of tissues obtained
      from fetuses, newborns, and pouch young were examined via polyacrylamide gel
      electrophoresis of the G6PD protein. As in adults, G6PD phenotypes in these
      developmental stages were highly skewed in favor of the maternal allele product,
      but in some tissues there was a marked increase in paternal allele expression
      with advancing developmental age. However, even by 42 days of post-partum
      development, expression of the paternal Gpd allele had not attained the adult,
      tissue-specific activity pattern. Our findings indicate remarkable developmental
      changes in the activity of the paternal allele in several tissues/organs
      continuing well into mid pouch-life stages and beyond. Specifically we found that
      1) a substantially repressed paternal Gpd gene is present in the cells of female
      stage 29 fetuses and later developmental stages, 2) the activity state of the
      paternal Gpd gene is not fixed during early embryonic development in this
      species, 3) major changes in paternal Gpd expression occur in advanced
      developmental stages and comprise a maturation of the gene expression pattern
      during ontogeny, and 4) alterations of paternal Gpd allele activity during
      development occur in a tissue-specific manner.

PMID- 7641418
TI  - Antitumor reactivity induced by liposomal MTP-PE in a liver metastasis model of
      colon cancer in the rat.
AB  - The antitumor effects of muramyl tripeptide phosphatidylethanolamine,
      incorporated within the lipophilic phase of liposomes (lipMTP-PE) were studied
      using a model of liver metastasis of colon cancer in the rat. Intravenous
      immunotherapy with lipMTP-PE, when started 2 days before the inoculation of tumor
      cells and given twice a week, significantly reduced subsequent tumor growth in
      the liver. The main effect of treatment appeared to be a substantial local
      increase in the number of tumoricidal macrophages and lymphocytes. Tumor cell
      lysis by isolated macrophages in vitro, however, appeared not to be elevated
      above the level triggered by tumor growth alone. Therefore, the observed
      therapeutic effect of lipMTP-PE probably results from a combination of (1) an
      increase in the number of cytotoxic macrophages at the onset of metastatic growth
      in the liver, thus increasing the probability of lethal contacts between
      tumoricidal effectors and tumor cells and (2) indirect effects of lipMTP-PE, via
      the induction of cytokine production by liver macrophages, leading to increased
      numbers and/or activity of cytotoxic lymphocytes and natural killer cells.

PMID- 7641419
TI  - Human melanoma invasion and metastasis enhancement by high expression of
      aminopeptidase N/CD13.
AB  - Aminopeptidase N/CD13 is a Zn(2+)-dependent exoprotease present on the cell
      surface as a transmembrane protein. Our previous studies using aminopeptidase
      inhibitors and antibodies demonstrated that aminopeptidase N is involved in the
      degradation and invasion of the extracellular matrix (ECM) by metastatic tumor
      cells. In the present study we transfected human A375M melanoma cells with
      eukaryotic plasmid expression vectors that contained full length cDNA of
      aminopeptidase N/CD13 and examined their characteristics. The transfectants that
      expressed extremely high levels of aminopeptidase N/CD13 degraded type IV
      collagen and invaded ECM more actively than the parental and control vector
      transfected cells. Furthermore, the aminopeptidase N/CD13-transfected A375M cells
      had significantly augmented lung colonizing potential in nude mice. The results
      show that the aminopeptidase N/CD13 plays an active role in degradation and
      invasion of ECM and may be involved in the molecular mechanisms of blood-borne
      metastasis.

PMID- 7641420
TI  - Control pathways of the 67 kDa laminin binding protein: surface expression and
      activity of a new ligand binding domain.
AB  - A number of papers have been published on the clinical correlation of the
      expression of the 67 kDa laminin binding protein (LBP) with the metastatic
      potential of solid tumors. Both mRNA and protein expression levels have been
      reported, but both the relationship between them and the molecular nature of the
      67 kDa surface product remain unclear. We have utilized a homotypic
      overexpression system to investigate the cell surface presentation of the 67 kDa
      LBP and the contribution of this protein to the invasive phenotype of cultured
      cell lines. We report here that the cellular mRNA levels do not directly reflect
      the levels of the 67 kDa LBP observed on the cell surface in this overexpression
      system. Methotrexate amplification of transfected plasmids expressing the 67 kDa
      LBP leads to an initial elevation of both the LBP mRNA and surface protein
      levels. This is accompanied by an altered, more flattened, cell morphology.
      Later, apparent adaptation of the cells to methotrexate is accompanied by a down
      regulation of the surface expression of the protein. mRNA levels, however, remain
      elevated. A nine amino acid sequence, CDPGYIGSR (peptide 11), within the beta
      chain of laminin 1 has been identified as a probable binding domain for the 67
      kDa LBP. Previous studies have identified a region of the 67 kDa LBP which may be
      involved in laminin interaction, although not necessarily via the peptide 11
      domain. We have identified a second site within the amino acid coding sequence of
      the 67 kDa LBP which also shows biological activity both in vitro and in vivo. A
      peptide with this sequence, LBP residues 205-229, binds laminin-1 in a peptide 11
      inhibitable manner. The receptor-derived peptide modulates invasion of basement
      membrane matrix in vitro and inhibits experimental lung colony formation when
      injected along with B16BL6 mouse melanoma cells. However, pretreatment of the
      melanoma cells with the peptide enhances lung colony formation. Thus, the
      interaction of the 67 kDa LBP with basement membrane matrix appears to involve a
      complex series of events including multiple adhesive sites and tight regulation
      of cell surface expression.

PMID- 7641421
TI  - Hyaluronic acid secreted by mesothelial cells: a natural barrier to ovarian
      cancer cell adhesion.
AB  - The adhesion to mesothelial monolayers of eight cultured ovarian tumour cell
      lines was studied in multiwell plates as a model for some of the interactions of
      ovarian cancer in the peritoneal cavity. When only the upper half of the
      conditioned medium (CM) from a confluent mesothelial cell culture was aspirated,
      the adhesion of the tumour cells was low (3.5%-36%). When the medium was removed
      completely the adhesion increased. The tumour cell lines showing the greatest
      enhancement of adhesion were those which had previously been shown to express the
      highest amounts of CD44. By adding erythrocyte suspensions to mesothelial cells
      it was shown that there was a pericellular coat around the mesothelial cells that
      could be destroyed by aspirating the medium, or by treating the medium with
      hyaluronidase (Hase). Treatment of the CM with Hase also considerably increased
      tumour cell adhesion. Furthermore, CM was shown to contain high amounts of
      hyaluronic acid (HA). HA blocked adhesion in the absence of CM, but the effect
      was not as large as that produced by the pericellular coat. It is proposed that
      pericellular HA produced by mesothelial cells has an important role in the
      invasion of ovarian tumour cells in the peritoneal cavity.

PMID- 7641422
TI  - Localization of messenger RNA for tissue inhibitor of metalloproteinases-1 and
      type IV collagenases/gelatinases in monkey hepatocellular carcinomas.
AB  - Studies of tissue inhibitors of metalloproteinases (TIMPs) suggest that one of
      their main functions is to inhibit metalloproteinase (MMP) activity and thus
      prevent tumor invasion by preserving extracellular matrix (ECM) integrity. In the
      present study we examined the distribution of transcripts for TIMP-1, MMP-2 and
      MMP-9 in monkey hepatocellular carcinoma tissues. In situ hybridization
      demonstrated elevated levels of TIMP-1 transcripts in fibrous tissue septa, tumor
      inflammatory infiltrate, tumor blood vessels and in expanded portal areas.
      However, elevated transcripts for MMP-2 and MMP-9 were found only in tumor
      inflammatory infiltrate. In lung metastasis high levels of TIMP-1 transcripts
      were found in the stromal cells surrounding necrotic tumor nodules, in tumor
      blood vessels, and in mesothelial cells. MMP-9 transcripts were elevated at the
      periphery of the necrotic tumor nodules. These findings suggest that TIMP-1 and
      type IV collagenases/gelatinases can be independently regulated in vivo and that
      TIMP-1 may have functions in ECM remodeling which are unrelated to inhibition of
      MMP activity.

PMID- 7641423
TI  - Sarcomatous lesions in CBA female mice treated with 1,2-dimethylhydrazine:
      independent primaries or metastases?
AB  - CBA female mice treated with 1,2-dimethylhydrazine (DMH) alone or in combination
      with oestradiol dipropionate (EP) or ascorbic acid (AA) developed, as expected, a
      high incidence of uterine sarcomas. In addition, sarcomatous lesions at unusual
      sites (mainly in the forestomach) were evident. The incidence of sarcomatous
      lesions at other sites was 53/220 in mice having uterine sarcomas and 0/186 in
      mice treated with DMH but without uterine sarcomas. The difference between the
      two groups was highly statistically significant (P < 0.001) and demonstrates non
      coincidental association of the above sarcomatous lesions with uterine sarcomas.
      Uterine sarcomas which presented in association with lesions at other sites were
      of a larger size than those found in isolation, and the difference in weights in
      three out of four groups was statistically significant (P = 0.008, 0.035 and
      0.011). Histologically, sarcomatous lesions were similar in structure to those of
      uterine sarcomas, i.e. were of a fibroblastic-histiocytic nature with admixture
      of giant cells. On the basis of the above data the sarcomatous lesions described
      appear to represent uterine sarcoma metastases rather than independent primary
      tumours. AA did not have any influence on carcinogenesis induced by DMH alone but
      inhibited the growth of uterine sarcomas (whether or not they were associated
      with other sarcomatous lesions) induced by DMH combined with oestradiol
      dipropionate.

PMID- 7641426
TI  - Perimalleolar tendon transfer to the os calcis for triceps surae insufficiency in
      patients with postpolio syndrome.
AB  - Twelve patients (14 feet) with the diagnosis of postpolio syndrome underwent
      patients-specific transfer of perimalleolar tendons to the os calcis for triceps
      surae insufficiency. One to 5 tendons were transferred, for a resulting mean
      muscle strength of Grade 3 at a mean followup of 2.7 years. At final followup, 7
      patients were restudied with ankle plantar flexion torque measurements, range of
      motion, and gait analysis. Patients reported subjective improvements in endurance
      (86%), pain (90%), and ambulatory distance (50%). No progression of foot
      deformity was noted. Three of 5 patients became brace free. After tendon
      transfer, patients recorded increased ankle plantar flexion torque strength (80%)
      and an increase in 1 grade of muscle strength (29%). There was no significant
      change in gait velocity, stride length, or heeloff time between pre- and
      postoperative gait analysis. No tenodesis effect was observed. In conclusion,
      perimalleolar tendon transfers for triceps surae insufficiency in postpolio
      patients was effective in decreasing subjective complaints, arresting progressive
      foot deformity caused by muscle imbalance, and increasing plantar flexion
      strength, whereas the results of gait analysis failed to show significant
      improvement.

PMID- 7641424
TI  - Inhibition of cancer cell motility and invasion by interleukin-12.
AB  - Tumour cell motility and attachment are crucial requirements in the formation of
      metastatic lesions. These properties are affected by a number of cytokines
      including hepatocyte growth factor/scatter factor (HGF/SF) and several
      immunoregulatory proteins, including interleukin-12 (IL-12). Although IL-12 has
      been reported to exhibit potent anti-tumour effects in vivo, a direct effect of
      IL-12 on cancer cells has not been reported. We show here that IL-12 directly
      inhibited the attachment of the human colon cancer cell lines HRT18, HT29 and
      HT115 to Matrigel, HGF/SF-stimulated cell motility and HGF/SF-induced cell
      invasion through a reconstituted basement membrane. IL-12 did not affect the
      growth of these cell lines. Flow cytometry, Western analysis and
      immunohistochemistry revealed an up-regulation of E-cadherin cell-surface
      adhesion molecules. These direct effects of IL-12 on colon cancer cells suggest a
      potentially important role for IL-12 in metastasis.

PMID- 7641425
TI  - Micromotion of the acetabular component and periacetabular bone morphology.
AB  - The quality of the periacetabular bone might be an explanation for the increase
      in the rate of socket loosening seen radiographically in patients with rheumatoid
      arthritis as compared with patients with osteoarthrosis. Early implant
      micromotion, as measured by roentgen stereophotogrammetric analysis, is of
      predictive value with regard to long time retention. For uncemented porous
      sockets, the initial fixation might be decisive for the degree of bone ingrowth.
      Roentgen stereophotogrammetry was used to study cemented Charnley acetabular
      components in 32 hips with rheumatoid arthritis and 30 hips with osteoarthrosis,
      and uncemented Harris-Galante acetabular components in 19 hips with
      osteoarthrosis. Micromotions as long as 24 months after surgery were related to
      the periacetabular cancellous bone quality, as assessed by histomorphometric
      methods from samples taken during surgery. Acetabular components migrated more in
      hips with rheumatoid arthritis than in those with osteoarthrosis (p < 0.04). Hips
      with rheumatoid arthritis had approximately 4 times more nonmineralized bone than
      hips with osteoarthrosis (p < 0.0002). However, within each diagnostic group, no
      correlation was found between migration and the degree of mineralization (r < or
      = 0.24, p > or = 0.07). Migration of uncemented acetabular components did not
      correlate with the histomorphometric variables (r < or = 0.20, p > or = 0.42).
      Histomorphologic characteristics of the periacetabular trabecular bone do not
      seem to be of importance for acetabular component micromotion.

PMID- 7641427
TI  - Idiopathic carpotarsal osteolysis with Bartter's syndrome. A case report and
      review of the literature.
AB  - Idiopathic carpotarsal osteolysis is 1 of the rare types of disappearing bone
      diseases characterized by painful limitation of movement and deformity of the
      wrist and tarsal joints, and associated with frequent episodes of joint
      inflammation and a radiographic appearance of osteolysis. Reported here is an 8
      year-old girl with idiopathic carpotarsal osteolysis and Bartter's syndrome with
      significantly decreased re-absorption of chloride at distal renal tubules, low
      level of serum potassium, a metabolic alkalosis, and high levels of aldosterone
      and renin. Bartter's syndrome associated with idiopathic carpotarsal osteolysis
      has not been published previously. The typical plantar nodule in this patient
      confirmed the presence of fibromatosis with aggressive histologic signs in light
      and electron microscopic examination.

PMID- 7641428
TI  - Shock-absorbing effect of shoe insert materials commonly used in management of
      lower extremity disorders.
AB  - The efficacy of 3 shock-absorbing materials was compared by determining impact
      characteristics with a drop test method and also by testing the effect of each
      material when used as a shoe insert in 16 asymptomatic subjects. Peak vertical
      ground reaction force (F1, F2, F3) and temporal force factors (T1, T2, T3) were
      obtained with a force plate at a high-frequency sampling rate. Impact force,
      impact time, impact slope, and impact energy were determined. A standard weight
      was dropped from 3 heights on each material covering the force plate while
      reduction of peak force was compared. Impact force was attenuated most
      effectively by Insert 3 (polymeric foam rubber) and averaged 11% less than that
      in shoes without inserts. Impact time was increased for all 3 inserts. Impact
      slope and impact energy were reduced significantly in Insert 3. There was a
      significant difference in peak vertical force F1 for all 3 inserts, in vertical
      force F2 for Insert 2 (viscoelastic polymeric material), and in vertical force F3
      for Insert 2. Drop-test studies showed that at all ball heights, the highest mean
      peak force was observed consistently in Insert 2.

PMID- 7641429
TI  - Ultrasound for the early diagnosis of fracture healing after interlocking nailing
      of the tibia without reaming.
AB  - Fourteen fractures (8 open, 6 closed) were treated with small-diameter
      interlocking tibial nails and observed for at least 1 year. Radiographs were
      obtained to monitor the maintenance of reduction and fracture healing. The
      treating orthopaedic surgeon was blinded to the results of ultrasound studies,
      which were obtained at 2-week intervals for 10 weeks postoperatively and read by
      a radiologist who was blinded to the clinical and radiographic progress.
      Ultrasound correctly predicted fracture healing in all 9 fractures that
      subsequently progressed to fracture union. Of the 5 fractures that did not heal
      and required secondary procedures, ultrasound predicted delayed healing in 4
      fractures. Overall, ultrasound was able to predict fracture healing before it was
      radiographically evident. Ultrasound may provide important prognostic information
      concerning tibial fracture healing after treatment using interlocking nails
      without reaming. Additional study is warranted.

PMID- 7641430
TI  - The effects of lasers and electrosurgical devices on human meniscal tissue.
AB  - The purpose of this study was to evaluate the effects of various laser
      wavelengths on human meniscal tissue in vitro and to compare them with the
      effects of electrosurgical devices. The carbon dioxide (CO2) laser produced the
      best cutting and ablating effects among the infrared lasers, although the contact
      neodymium:yttrium-aluminum-garnet (Nd:YAG) and holmium:YAG (Ho:YAG)lasers were
      nearly as satisfactory, offering the additional advantage of fiberoptic
      capability and the ability to be used in saline. The free-beam Nd:YAG laser and
      coagulation mode electrosurgical device produced unacceptably severe thermal
      changes. The excimer laser at 308 nm produced the best tissue effect and caused
      no detectable adjacent thermal change in the tissue.

PMID- 7641432
TI  - Ambulatory ability after hip fracture. A prospective study in geriatric patients.
AB  - Three hundred thirty-six community-dwelling, previously ambulatory, geriatric
      patients with hip fracture were observed prospectively to determine ambulatory
      ability at a minimum followup of 1 year. One hundred thirty-seven (41%) patients
      maintained their prefracture ambulatory ability at a minimum followup of 1 year;
      134 (40%) patients remained ambulatory but became more dependent on assistive
      devices; 39 (12%) previous community ambulators became household ambulators, and
      26 (8%) patients became nonfunctional ambulators. Analysis was performed to
      determine which pre- and postinjury factors were predictive of failure to recover
      ambulatory capacity 1 year after fracture. Potential predictor variables analyzed
      included age, gender, number of comorbid conditions, prefracture ambulatory
      ability, prefracture living situation, fracture type, American Society of
      Anesthesiologists rating of operative risk, type of surgery, and number of
      postoperative complications. Multiple logistic regression analysis identified
      significant contributions of age, prefracture ambulatory ability, American
      Society of Anesthesiologists rating of operative risk, and fracture type to
      ambulatory recovery.

PMID- 7641431
TI  - Use of capacitive coupled electric fields in stress fractures in athletes.
AB  - The authors report the results of an open study on the treatment of stress
      fracture in athletes by capacitive coupling, a bone healing stimulation method
      promoting bone formation by application of alternating current in the form of a
      sinusoidal wave. Twenty-five lower-limb (navicular, 2nd and 5th metatarsal,
      tibia, fibula, and talus) stress fractures in 21 athletes (mean age, 21.8 years
      old) were treated. The mean stimulation time was 52 days (navicular fractures, 60
      days). Twenty-two fractures were healed, 1 was not healed, and 2 were improved.
      This preliminary report shows that capacitive coupling can be used safely in the
      treatment of these stress fractures.

PMID- 7641433
TI  - Shepherd's crook deformity with an intracapsular femoral neck fracture in fibrous
      dysplasia.
AB  - A shepherd's crook deformity with an intracapsular femoral neck fracture in the
      fibrous dysplasia of a 19-year-old woman is reported. The deformity and fracture
      were treated by bone grafting using a single fibula through the femoral neck to
      its head, and corrective valgus osteotomy. Blood flow measurement using
      electrochemically generated hydrogen clearance was useful in evaluating avascular
      necrosis of the femoral head affected by tumorous tissue. Osteosynthesis combined
      with a fibular graft, and corrective valgus osteotomy after proper evaluation of
      the blood flow in the femoral head, is a reliable procedure for the treatment of
      shepherd's crook deformity associated with an intracapsular femoral neck
      fracture.

PMID- 7641434
TI  - Stress fractures of the femoral diaphysis in young children. A report of 2 cases.
AB  - Stress fractures of the femoral diaphysis in young children are rare. Pain and an
      antalgic gait are the most common features. There is usually no history of either
      trauma or a recent increase in physical activities. Initial radiographs may be
      normal. Technetium bone scanning is the most sensitive method of early diagnosis,
      but may not be diagnostic. Computed tomography and magnetic resonance imaging are
      useful in early confirmation of the diagnosis. Serial radiographs will show
      maturation of the periosteal new bone with evidence of repair. Biopsy should be
      avoided, except in cases of obvious neoplasm shown by computed tomography or
      magnetic resonance imaging, or in cases with progressive cortical destruction
      shown on serial radiographs, because fracture callus may be difficult to
      distinguish from osteosarcoma. Treatment consists of protected weight bearing and
      activity restriction until resolution of symptoms and radiographic evidence of
      healing.

PMID- 7641435
TI  - Osteoid osteoma of the hip. Percutaneous resection guided by computed tomography.
AB  - Seven patients with a presumptive diagnosis of osteoid osteoma located at the hip
      were treated with percutaneous resection of the nidus through computed tomography
      guidance. Histologic confirmation was obtained in 5 of the 7 patients. The
      average hospital stay was 27 hours. At followup, from 12 to 40 months, all
      patients remain asymptomatic. This procedure presents potential advantages that
      traditional open surgery techniques do not have.

PMID- 7641436
TI  - MIC2 detection in tumors of bone and adjacent soft tissues.
AB  - The diagnosis of Ewing's sarcoma has been based classically in large part on the
      exclusion of other similar small round-cell tumors by light microscopic and
      histochemical criteria. This study was undertaken to explore the use of a
      recently developed immunohistochemical stain directed against the glycoprotein
      p30/32MIC2 antigen (the gene product of MIC2), as a diagnostic tool and as a
      probe for the examination of potential interrelationships among the putative
      members of the family of peripheral primitive neuroectodermal tumors. Fifty-six
      small round-cell tumors of bone were selected for study from the files of the
      Armed Forces Institute of Pathology and Rhode Island Hospital; all tissues had
      been formalin fixed and paraffin embedded. Nine of 10 Ewing's sarcomas were MIC2
      positive, as were 2 of 3 atypical Ewing's sarcomas (small round-cell tumors that
      diverged from the classic pattern of Ewing's sarcoma by exhibiting a greater
      degree of cytologic atypia and pleomorphism), and 7 of 8 Askin tumors of the
      thoracopulmonary region. Ten of 11 mesenchymal chondrosarcomas, 1 primitive
      neuroectodermal tumor of bone, 10 small cell osteosarcomas, 10 malignant
      lymphomas, and 3 sarcomas of bone (not additionally subclassified) were negative.
      The finding of MIC2 positivity in the majority of Ewing's sarcomas and Askin
      tumors provides additional support for earlier proposals (based on a shared
      cytogenetic abnormality, among other criteria) that these lesions be considered
      members of the same family, the peripheral primitive neuroectodermal tumors. The
      present study, drawing on archival and current case material (including
      decalcified and undecalcified specimens), indicates that neither the specimen age
      nor the application of any of a variety of decalcification solutions appears to
      adversely influence MIC2 staining of paraffin-embedded tissues. This suggests
      that this antibody has use in retrospective and prospective studies. The rare
      occurrence of false negative (in the case of Ewing's sarcoma) and positive
      results in tumors other than peripheral primitive neuroectodermal tumors (as in 1
      of the mesenchymal chondrosarcomas) suggests that MIC2 staining should not be
      relied on as the sole criterion for identification or exclusion of Ewing's
      sarcomas and related tumors.

PMID- 7641437
TI  - Pulmonary resection for metastatic soft tissue sarcomas.
AB  - The therapeutic results of pulmonary resection for metastatic soft tissue
      sarcomas were analyzed. From 1970 to 1992, 23 patients (15 male and 8 female)
      underwent 40 pulmonary resections for metastatic soft tissue sarcomas. Nine (39%)
      patients had multiple thoracotomies for recurrences (range, 2-6). The 5-year
      actuarial overall survival was 32% (median, 28 months). Statistical analysis
      showed that age, gender, location of primary tumor, histology, site of pulmonary
      metastasis, tumor doubling time, or chemotherapy did not impact on survival.
      Significant prognostic factors associated with improved survival (p < 0.05)
      included a disease-free interval, and completeness and extent of the initial
      pulmonary resection. Patients with disease-free intervals > or = 12 months
      survived longer (5-year survival, 48.5%) than patients with disease-free
      intervals < 12 months (12%). Patients who could be rendered free of disease at
      their initial thoracotomy, without extended chest-wall resection, achieved a
      better outcome (5-year survival, 44%) than the others (5-year survival, 0%).

PMID- 7641438
TI  - Adamantinoma of the olecranon. A report of a case with serial metastasizing
      lesions.
AB  - Adamantinomas are slow-growing, invasive malignant tumors. Although the majority
      of cases have arisen in the tibia, these aggressive tumors have been reported in
      most of the long bones. This is the first known report of a patient with
      adamantinoma of the olecranon, an unusual site for this lesion. However, the
      patient not only had a novel site of appearance of the tumor and local recurrence
      of the disease, but also had a series of distant, isolated, bony tissue
      metastases before a fatal metastasis to the lung within a 9-year period. Although
      metastasis to other bony sites has been reported, a series of metastases to bony
      and soft tissues is unusual.

PMID- 7641439
TI  - Giant-cell tumor of the distal phalanx of the hand in a child.
AB  - Giant-cell tumor of bone in the distal phalanx is rare, as is its clinical
      occurrence in children. A case of a 10-year-old girl with giant-cell tumor in the
      distal phalanx of the left thumb is reported, and a literature review of
      phalangeal giant-cell tumor of the hand is presented. The tumor was curetted, and
      after 2.5 years there was no recurrence.

PMID- 7641440
TI  - Efficacy of immediate postirrigation culture in the treatment of upper-extremity
      abscesses.
AB  - A retrospective chart review of 192 patients of the musculoskeletal infection
      ward at the authors' facility was performed to assess the value of immediate
      postirrigation cultures in the treatment of acute soft tissue infections of the
      upper extremity. Twenty-two patients (11.5%) had postirrigation cultures with an
      organism that was not present in the preirrigation cultures. All of those
      organisms not previously found were gram-positive organisms, and no changes were
      necessary in the initial antibiotic regimes. Immediate postirrigation cultures
      did not prove to be effective in the information they provided related to
      treatment of acute soft tissue infections of the upper extremity.

PMID- 7641441
TI  - In vitro analysis of laser meniscectomy.
AB  - Partial meniscectomies were performed on 32 fresh human meniscal autopsy
      specimens. The following laser systems were tested: carbon dioxide (CO2),
      neodymium:yttrium aluminum garnet (Nd:YAG), potassium titanyl phosphate (KTP),
      holmium:YAG (Ho:YAG), and excimer. Meniscectomies with these lasers were compared
      with scalpel, mechanical, and electrocautery meniscectomies. Lasers were applied
      to specimens in and out of normal saline. Routine hematoxylin and eosin and
      sirius red sections were prepared for each specimen, and the depths of thermal
      changes were analyzed. Scanning electron microscopy was used to visualize the
      meniscectomy interface. Among these specimens, the scalpel and mechanical
      meniscectomies showed the least extension of cellular changes (range, 10-15 nm).
      The excimer laser caused the least tissue changes of the lasers tested. Tissue
      changes were less extensive with the pulsed CO2 laser than with the holmium:YAG,
      neodymium:YAG, and KTP lasers. Scanning electron microscopy showed that use of
      the scalpel meniscectomy resulted in the smoothest meniscectomy edge, followed by
      use of the excimer, CO2, holmium:YAG, neodymium:YAG, and KTP lasers. The most
      surface disruption occurred with electrocautery. Meniscectomies under saline
      required more energy and took longer in each case, with the holmium:YAG,
      neodymium:YAG, and CO2 laser cutting the best. Saline meniscectomies showed less
      thermal change. The CO2 and KTP lasers cut best in air.

PMID- 7641442
TI  - Electromyograph analysis of the popliteus muscle in level and downhill walking.
AB  - It has been proposed that the popliteus muscle is a source of lateral knee pain,
      typically after downhill activities. Electromyography of the popliteus muscle was
      recorded in 9 normal subjects during level walking, downhill walking, and walking
      downhill wearing a 40-lb backpack (to simulate hiking). Popliteal muscle
      intensity during the midstance phase of walking downhill with weights increased
      significantly over that of level walking (30% versus 13%, respectively) (p <
      0.05). There was a nonsignificant trend (p = 0.07) for a similar increase at
      terminal swing (51% versus 36%). Significantly greater knee flexion was recorded
      at loading response, midstance, and terminal stance (p < 0.01) during both
      downhill trials as compared with level walking. Initial contact position showed
      no differences. Velocities for downhill walking (72.9 m/min) and downhill walking
      with weights (71.1 m/min) were significantly less than those of level walking
      (83.9 m/min) (p < 0.01). Stride analysis showed no significant difference in
      stance phase duration or in initial double-limb support times between level
      walking and either downhill condition. These data suggest that increased
      popliteal muscle activity during midstance in downhill walking with weights is in
      response to weight bearing with an increased load on a flexed knee. Increased
      Electromyographic activity may be associated with overuse of the popliteus
      muscle.

PMID- 7641443
TI  - Early fracture callus in the diaphysis of human long bones. Histologic and
      ultrastructural study.
AB  - The medullary callus and the periosteal callus of fractured long bones were
      studied in 26 adults undergoing open reduction and internal fixation of closed
      diaphyseal fractures that occurred 1 to 21 days before surgery. In the 1st week
      after fracture, a progressive increase was observed in the number of polymorphic
      mesenchymal cells in the medullary callus and of fibroblast-like cells in the
      periosteum, where the first calcification foci were seen 7 days after injury. In
      the 2nd week after fracture, the medullary callus presented numerous mesenchymal
      cells, fibroblasts, and newly formed capillaries, whereas the inner periosteal
      layer showed many osteoblast-like cells. New bone trabeculae were first seen in
      the periosteal callus 12 days after injury. In the 3rd week after fracture, new
      trabecular bone appeared in the medullary callus. Cartilage also became apparent
      in the medullary and periosteal callus but remained limited in amount.
      Calcification within cartilage was first observed in the periosteum 18 days after
      fracture. The process of fracture healing in long bones in humans is similar,
      though not identical, to that described for long bones in laboratory animals.

PMID- 7641444
TI  - Assessment of argyrophilic nucleolar organizer region quantification in benign
      and malignant bone tumors.
AB  - Quantification of argyrophilic nucleolar organizer regions has been proposed as a
      technique that may aid in diagnosing and predicting the biologic behavior of a
      variety of neoplasms. A 1-step silver staining technique was used to identify and
      quantify argyrophilic nuclear organizer regions in a series of 96 bone tumor
      specimens. Malignant bone tumors had a higher mean argyrophilic nuclear organizer
      region count (3.05 +/- 0.82) than giant cell tumors (1.39 +/- 0.14, p < 0.001)
      and benign bone tumors (1.51 +/- 0.42, p < 0.001). Despite these differences in
      mean counts, an overlap of argyrophilic nuclear organizer region scores was
      observed in some benign and malignant cases. The argyrophilic nuclear organizer
      region counts of the osteosarcomas were analyzed to determine whether they
      correlated with tumor behavior. The mean argyrophilic nuclear organizer region
      count of specimens from patients in whom metastatic disease developed was not
      significantly different than that of patients who remained disease free.

PMID- 7641445
TI  - Strength of the pin-bone interface of external fixation pins in the iliac crest.
      A biomechanical study.
AB  - The iliac crest is a frequent insertion site for external fixation pins in
      treating unstable pelvic or acetabular fractures and in iliofemoral distraction
      for superiorly dislocated hips. The pin-bone interface is critical for the
      success of treatment, but studies of the iliac crest are lacking. The purpose of
      this study was to investigate the strength of the pin-bone interface of different
      pins and different insertion methods. Four types of commercial pins, Wagner pins,
      Orthofix cortical and cancellous screws, and AO pins, were driven into sheep
      iliac crests by 2 methods: the intercortical and the transcortical. Specimens
      were tested for pullout and bending with an Instron testing machine (Model 1343)
      at a extension rate of 0.02 mm/sec to failure. The results revealed that the
      intercortical method had a stronger pullout force than the transcortical in all
      types of screws (p < 0.05), probably caused by longer insertion in the bone. In
      the pullout tests, the Wagner pins were the strongest and the Orthofix cancellous
      screws were the weakest. There were no differences in bending. In the iliac
      crest, the intercortical method was the better way of driving pins, and the new
      Orthofix screws were not proven to be stronger than the Wagner pins, nor were the
      cancellous screws more suitable than the cortical ones.

PMID- 7641446
TI  - Anterior versus posterior provisional fixation in the unstable pelvis. A
      biomechanical comparison.
AB  - Pelvic ring injuries with associated hemorrhage often require provisional
      fixation to achieve tamponade. Biomechanics information regarding these
      provisional fixators is unknown. Six fresh-frozen cadaveric pelvic specimens were
      physiologically loaded, first intact and then after each of the following
      modifications: disrupted--unilateral superior and inferior rami osteotomies,
      ipsilateral anterior and posterior sacroiliac joint, and sacrospinous and
      sacrotuberous ligament disruption; disrupted and with placement of a Ganz pelvic
      resuscitation clamp; and disrupted and with placement of a simple anterior 2-bar
      external fixator. This injury resulted in significant motion at the disrupted
      rami and the injured sacroiliac joint, compared with the intact pelvic specimen.
      Motions at the superior ramus and injured sacroiliac joints were significantly (p
      < 0.05) greater than the intact specimen, with both the external fixator and the
      Ganz clamp. Motions at the superior ramus and injured sacroiliac joints were not
      significantly (p < 0.05) different when comparing the Ganz clamp to the external
      fixator. However, the anterior external fixator decreased motion to a greater
      degree at the disrupted rami, whereas the Ganz clamp decreased motion to a
      greater degree at the disrupted sacroiliac joint.

PMID- 7641447
TI  - Bone graft harvest site as a determinant of iliac crest strength.
AB  - Bone graft harvest site fracture can occur after removal of bone from the
      anterior iliac crest. No biomechanically proven guidelines for safe removal of
      bone exist. Cadaveric hemipelves were tested in a materials testing system
      machine, with the harvest site occurring 15-mm posterior to the anterosuperior
      iliac spine in 8 specimens and 30-mm posterior in 7 specimens. These pelves were
      then tested to failure by simulating avulsion fractures caused by the forces of
      the flexors of the hip. Average force at failure was 783 N (standard deviation,
      +/- 333 N) in the 15-mm group and 1917 N (standard deviation, +/- 735) in the 30
      mm group. This study provides objective data which demonstrate that harvest 30 mm
      posterior to the anterosuperior iliac spine weakens the iliac crest less than
      harvest 15 mm posterior to the anterosuperior iliac crest. To minimize the
      possibility of iliac crest fracture after bone graft harvest, bone should be
      removed at least 30 mm from the anterior superior iliac spine.

PMID- 7641448
TI  - Elbow injuries in athletes. A review.
AB  - Elbow injuries are becoming more common as increasing numbers of people
      participate in throwing and racquet sports. The understanding and treatment of
      elbow injuries is becoming more sophisticated in conjunction with better
      noninvasive and invasive diagnostic techniques. The majority of injuries to the
      elbow in the athlete are chronic, overuse injuries. These injuries are the result
      of repetitive intrinsic or extrinsic overload, or both, resulting in microrupture
      of soft tissue such as ligament or tendon. In children, apophyses, being the
      weakest link in the immature musculoskeletal system, are susceptible to stress
      injuries. Elbow injuries are most commonly caused by valgus stress, from throwing
      or axial compression, resulting in increased force absorbed by the medial elbow.
      With repetitive valgus stress, patients may develop chondromalacia, loose bodies
      in the posterior or lateral compartments, injury to the ulnar collateral
      ligament, myotendinous injury to the flexor-pronator muscle group,
      osteochondritis dissecans, or ulnar neuritis. The purpose of this paper is to (1)
      define the significance of elbow injuries in athletics, (2) review the anatomy
      and biomechanics of the elbow, and (3) discuss the prevention and treatment of
      elbow injuries.

PMID- 7641449
TI  - A spectrophotometer analysis of light absorption in the human meniscus.
AB  - The spectrophotometer analysis of light absorption curves in human meniscal
      tissue showed a reproducible series of graphs for varying tissue thickness, age,
      zone, and sectioning plane. These data show water as the essential reason for
      light absorption in the infrared portion of the light spectrum. The excimer laser
      in the ultraviolet region, and wavelengths around 2000 nm in the infrared region,
      appeared to provide the best wavelength match for laser energy transfer and the
      cutting or ablating of meniscal tissue. On-going research into clinical
      applications should focus on these wavelengths.

PMID- 7641451
TI  - A tribute to Emile Letournel, MD (1927-1994).

PMID- 7641450
TI  - Soft tissue thigh mass in a 29-year-old man.

PMID- 7641452
TI  - Mechanisms of failure of modular prostheses.

PMID- 7641453
TI  - Toxic effects of chymopapain.

PMID- 7641454
TI  - A preliminary note on a new surgical-current generator. 1928.

PMID- 7641455
TI  - Mechanisms of meniscal tissue ablation by short pulse laser irradiation.
AB  - A new experimental technique was developed to study short-pulsed laser ablation
      of biologic tissues (human meniscus and bovine tibial bone), water, and acrylic.
      The experimental technique was based on interferometric monitoring of the motion
      of the tissue surface to measure its laser-induced expansion after irradiation.
      The thermoelastic expansion of these materials after laser irradiation under
      subablation threshold was examined to determine its role in the initiation of
      ablation. The experimentally observed surface expansion of cortical bone and
      acrylic was in agreement with theoretical predictions. The movement of meniscal
      tissue was similar to that shown by water. The latter 2 materials showed
      additional features consistent with the growth and collapse of cavitation
      bubbles. The exact role of cavitation in the irradiation of meniscal tissue by
      laser light remains unknown, but may represent a clinically important mode of
      tissue ablation and postirradiation trauma.

PMID- 7641456
TI  - Laser-assisted fibrin clot soldering of human menisci.
AB  - Fibrin mixtures have been used as a solder in conjunction with argon ion lasers
      to create strong tissue welds in several organ systems. An analogous method of
      meniscus repair could obviate the need for partial meniscectomy and its
      subsequent degenerative effects in a subset of meniscal tears. This study
      measured the in vitro tensile strength in 4 groups of human menisci (1-mm x 2-mm
      x 5-mm sections): (1) bisected menisci repaired with fibrin clot mixture, (2)
      bisected menisci bonded by fibrin clot mixture and exposure to argon laser energy
      (energy density, 60 W/cm2), (3) bisected menisci repaired with 2 interrupted
      sutures, and (4) untreated meniscal controls. After irradiation with argon ion
      laser energy, the tensile strength of the laser-assisted fibrin clot-bonded
      menisci increased 40-fold over that of nonirradiated fibrin clot-bonded menisci.
      Suture controls (0.515 +/- 0.221 MPa) had a higher tensile strength than the
      fibrin clot mixture and irradiated groups; however, the suture controls had only
      8.5% the strength of native menisci (6.081 +/- 0.221 MPa). Laser-assisted fibrin
      clot soldering may allow the opposing edges of a meniscal tear to be held
      together with a biologic scaffold, possibly inducing reparative cell migration
      and proliferation.

PMID- 7641457
TI  - Lateral retinacular release. The holmium:YAG laser versus electrocautery.
AB  - A retrospective study was conducted in which several parameters of postoperative
      recovery were compared between 2 groups of patients: 25 patients who had lateral
      retinacular release surgery in which the holmium:yttrium-aluminum-garnet (Ho:YAG)
      laser was used, and a control group of 17 patients who had the same surgery in
      which electrocautery was used. Postoperative recovery times of patients treated
      with the Ho:YAG laser were significantly decreased as compared with the recovery
      rates of patients in the control group. Morbidity also was reduced in the group
      for whom the laser was used. The results of this study indicate that the 2.1
      micron-wave-length, pulsed Ho:YAG laser can be used safely and effectively to
      perform lateral retinacular release surgery.

PMID- 7641458
TI  - The biological effects of carbon dioxide laser surgery on rabbit articular
      cartilage.
AB  - A pulsed carbon dioxide laser made predetermined superficial and deep
      (subchondral) lesions through arthrotomies on the femoral condyles of adult New
      Zealand rabbits. Twenty rabbits, including controls, were divided into acute, 1-,
      3-, 6-, and 12-month sacrifice groups. Early sacrifice groups showed some fibrous
      ingrowth from the deep lesions, but not the superficial lesions, and this was not
      seen in the 6- or 12-month groups. Cells below and adjacent to the laser lesions
      appeared viable when compared with controls. In each group studied, no histologic
      evidence of healing or fibrous covering in the superficial or deep laser lesions
      was found. No adverse clinical effects (synovitis, infection) were found in the
      laser groups, and the laser permitted excellent depth control during
      vaporization. However, the authors caution against irradiating articular
      cartilage.

PMID- 7641459
TI  - Acute and chronic response of articular cartilage to holmium:YAG laser
      irradiation.
AB  - A Ho:YAG (holmium-yttrium-aluminum-garnet) laser system operating at a wavelength
      of 2.1 microns has been introduced recently for use in arthroscopic surgery. The
      acceptability of this new tool will be determined not only by its ability to
      resect tissue, but also by its long-term effects on articular surfaces. Two
      studies were performed to evaluate the acute and chronic effects of the laser on
      cartilaginous tissue. The acute in vitro effects of 2.1-micron laser irradiation
      were evaluated, including measurement of ablation efficiency, ablation threshold,
      and thermal damage in meniscal and articular cartilage. To document the chronic
      effects on articular cartilage in vivo, a 10-week healing study was performed.
      Eight sheep weighing 30 to 40 kg underwent bilateral arthrotomy procedures.
      Multiple full-thickness and partial-thickness defects were created. Animals were
      euthanized at 0, 2, 4, and 10 weeks. The results of the healing study showed (1)
      no healing of full- or partial-thickness defects in hyaline cartilage at 10
      weeks; (2) fibrocartilaginous granulation tissue filling full-thickness defects
      at 2 and 4 weeks that was no longer evident at 10 weeks; (3) chondrocyte necrosis
      extending to > 900 microns distal to ablation craters at 4 weeks, with no
      evidence of repair at later dates; (4) chondrocyte hyperplasia at the borders of
      the damage zone at 2 weeks but not at euthanization occurring at later periods.

PMID- 7641460
TI  - Percutaneous laser disc nucleotomy.
AB  - In September 1988, the first laser decompression of a symptomatic contained
      bulging disc was performed in the United States. This author participated in a
      case study of 333 patients treated with the neodymium (Nd)-impregnated yttrium
      aluminum garnet (YAG) laser of 1064-nm wavelength. He also treated 117 patients
      with the potassium titanyl phosphate (KTP) laser of 532-nm wavelength. Detailed
      surgical techniques and followup statistics of the 117 patients treated with the
      KTP laser are presented and compared with those of a subset of 36 of the 333
      patients treated with the Nd:YAG laser. Of the 117 patients treated with the KTP
      laser, 23 patients were at the 2-year followup, and 46 patients at the 1-year
      followup, at the time of this writing. A statistically significant reduction in
      overall average patient pain was documented by disc level as a function of
      followup duration. Variation in average specific neurologic findings (knee jerk,
      reflex, toe strength, ankle jerk, pinprick, and Lasague's sign) by disc level as
      a function of followup duration was not significant. These procedures were
      accomplished with no major complications. The success rate based on a 2-year
      followup was 72%. The success rate with the Nd:YAG laser was very similar, at
      70%. These data provide encouraging information substantiating the validity of
      laser surgery for percutaneous disc nucleotomy.

PMID- 7641461
TI  - Laser biophysics for the orthopaedic surgeon.
AB  - The purposes of this paper are to review theoretical and practical aspects of
      laser-tissue interaction and to help the practicing orthopaedic surgeon
      understand basic laser terminology. Only with a full understanding of the laser's
      interaction with tissue and the jargon of laser physics can the orthopaedic
      surgeon fully be aware of the laser's potential as an orthopaedic tool as well as
      the laser's limitations.

PMID- 7641462
TI  - Carbon dioxide laser removal of polymethylmethacrylate.
AB  - Polymethylmethacrylate remains an excellent method of securing orthopaedic
      implants. However, revision surgery may be necessary when loosening of the
      prosthesis has occurred with symptomatology. Removal of polymethylmethacrylate
      during revision surgery can be difficult. Care must be taken to avoid damage to
      the remaining bone and surrounding soft tissue. This study was undertaken to
      characterize the efficacy of the carbon dioxide (CO2) laser for cement removal in
      vitro and in vivo. The CO2 laser did not damage adjacent bone or soft tissue via
      lateral heat transfer in vitro and in vivo. The maximum bone cortex temperature
      during CO2 laser removal was 56 degrees C. This was lower than the 60 degrees C
      temperature encountered during initial cement insertion and curing. The CO2 laser
      preferentially penetrates polymethylmethacrylate with absorption versus apparent
      relative reflection with bone. The products of vaporization from CO2 laser
      removal of polymethylmethacrylate were removed safely (to < 12.2 ppm) with a
      smoke evacuator without risk to the patient or operating room personnel. Removal
      of polymethylmethacrylate by CO2 laser was performed in 117 patients undergoing
      revision operations, including 78 total hip revisions, 33 total knee revisions, 3
      total elbow revisions, and 3 spine revisions. No perforation or fracture of bone
      occurred with the use of the laser. There was no statistical difference in
      surgical time, blood loss, infection rate, or hospital stay when the CO2 laser
      was used. There were no cases of osteonecrosis or obvious soft tissue necrosis
      caused by the laser. The infection rate was 3.4% (4/117) when the laser was used
      for cement removal.

PMID- 7641463
TI  - The excimer laser in orthopaedics.
AB  - This review details clinical and laboratory experience with the 308 nm XeCl
      excimer laser. This ultraviolet laser is not approved yet for use in arthroscopy,
      but has been shown to be extremely proficient for debridement of degenerate
      articular cartilage and meniscus. It has fewer advantages than conventional
      techniques for synovectomy, meniscectomy, and lateral release. Preliminary in
      vitro and in vivo studies were performed to investigate the character of laser
      irradiated articular cartilage and to search for evidence of regeneration. A
      model of arthritis was created in rabbits to test the effects of the laser.
      Partial-thickness cuts in articular cartilage also were irradiated to test for
      cartilage regeneration. In vitro results indicated that the cartilage was sealed,
      with only a negligible loss in thickness. The results of live rabbit studies
      initially showed a similar sealing under scanning electron and light microscopy;
      however, it tended to break down in time. The results of autoradiographic and
      histologic studies showed no evidence of cartilage regeneration. Recent evidence
      suggests that the laser may adversely affect chondrocyte vitality in a region
      beyond the region of visible damage. There is no evidence to suggest that the
      laser is mutagenic.

PMID- 7641464
TI  - Arthroscopic posteromedial visualization of the knee.
AB  - Arthroscopic visualization of the posteromedial compartment of the knee via an
      anterolateral portal is not commonly practiced, yet it is relatively simple, has
      low morbidity, and is of diagnostic and therapeutic value. This prospective study
      evaluates posteromedial visualization of the knee joint in a series of 117
      consecutive patients who underwent arthroscopy for diagnosis or treatment, or
      both, of 209 pathologic conditions. The technique was deemed simple to perform in
      78% of patients. It was found to be more difficult in knees with degenerative
      joint disease. Posteromedial visualization was found to be essential for
      diagnosis or treatment in 4% of the diagnosed conditions, and helpful in an
      additional 13%. The technique was most useful for tears of the posterior horn of
      the medial meniscus, some of which were not detected by visualization from the
      anteromedial compartment alone. Visualization of the posteromedial compartment
      was deemed adequate in 89% of the patients, and there was no morbidity.

PMID- 7641465
TI  - Anterior-posterior stability in partially conforming condylar knee replacement.
AB  - The purpose of the study was to estimate the anterior-posterior displacements
      that would occur with total knee prosthetic designs of different sagittal radii
      under functional conditions. A key question was whether some designs provided
      excessive constraint. Patients who had different total knee prosthetic designs
      were tested in a special rig where the AP drawer was measured under loaded and
      unloaded conditions. These same designs of total knee prostheses were then tested
      in a rig under different conditions of compressive and shear loads. Using these
      experiments as verification, a theoretical treatment was developed to predict the
      AP displacement for different activities. It was concluded that designs with low
      to moderate conformity required soft tissue restraint under more strenuous
      activities, or where high shear forces occurred under low compressive loads.
      Designs of moderate to high conformity could be fully self-stabilizing under all
      realistic conditions. However, for all designs, the AP displacement was only a
      few millimeters under functional loads, indicating that special care must be
      taken during surgery to avoid conflict between the condylar surfaces and the
      retained cruciate ligaments so that restriction of motion and excessive wear do
      not occur.

PMID- 7641466
TI  - Short-term results of hydroxyapatite-coated primary total hip arthroplasty.
AB  - One hundred consecutive patients who had Howmedica ABG total hip replacements, a
      system in which the femoral stem and the acetabular component are hydroxyapatite
      coated, during the period from September 1989 to January 1991 were studied
      prospectively. Clinical assessment using the d'Aubigne score showed that 96
      patients had an excellent score at a minimum of 2 years from the operation.
      Radiographic analysis, based on DeLee and Charnley criteria for the acetabular
      cup and on Gruen criteria for the femoral stem, showed equally good results.
      There was good initial stability of the cup and the metaphyseal portion of the
      stem, with a secondary increase of load transmission in Zones 2 and 6 with
      cortical and cancellous thickening.

PMID- 7641467
TI  - Interleukin-10 stimulates hematopoiesis in murine osteogenic stroma.
AB  - Bone marrow from 5-fluorouracil-treated mice support osteogenesis when cultured
      in the presence of beta-glycerophosphate and vitamin C. These cultures are unable
      to support the growth of granulocyte/macrophage colony-forming units for longer
      than 2 weeks. In contrast, granulocyte/macrophage colony-forming units were
      detected for more than 6 weeks in interleukin-10 (IL-10)-treated cultures. In
      addition, IL-10-treated cultures contain long-term culture initiating cells,
      suggesting the presence of pluripotent hematopoietic cells. Apparently, IL-10
      does not directly stimulate the proliferation of granulocyte/macrophage colony
      forming units. Interleukin-10 is unable to stimulate [3H]-thymidine incorporation
      or to increase the number of granulocyte/macrophage colony-forming units in cell
      suspensions harvested from untreated or interleukin-10-treated bone marrow
      cultures. Interleukin-10 acts via an indirect pathway. Because exogenous
      transforming growth factor-beta (TGF-beta) reverses IL-10's stimulatory activity
      on myeloid progenitors, IL-10 most likely works by blocking TGF-beta synthesis,
      which acts as an endogenous suppressor of hematopoiesis in osteogenic marrow
      cultures. This is shown further by the increased numbers of
      granulocyte/macrophage colony-forming units in cultures treated with neutralizing
      anti TGF-beta antibodies (1D11.16). Interleukin-10 and 1D11.16 change the
      cultured bone marrow stroma from an osteogenic into a hematopoietic morphology.
      It may be that by blocking endogenous TGF-beta production, IL-10 drives marrow
      mesenchymal cells away from osteogenic differentiation toward hematopoietic
      support.

PMID- 7641468
TI  - Bone morphogenetic proteins, bone marrow stromal cells, and mesenchymal stem
      cells. Maureen Owen revisited.
AB  - In postnatal mammals, there are persistent molecular signals and responding cells
      in bone to initiate osteogenesis and repair in response to trauma. The responding
      osteogenic precursor cells are of 2 categories: determined and inducible. The
      latter can be induced by demineralized bone matrix to form bone. Demineralized
      bone matrix consists of extracellular matrix and tightly associated bone
      morphogenetic proteins. The genes for bone morphogenetic proteins have been
      cloned, the recombinant proteins have been expressed, and currently their
      mechanism of action is being explored. Bone morphogenetic proteins are
      pleiotropic initiators of inducible osteogenic precursor cells. Bone
      morphogenetic proteins govern the 3 key steps in the osteogenic cascade:
      chemotaxis, mitosis, and differentiation. The receptors for bone morphogenetic
      proteins have been cloned and expressed and consist of 2 classes, Types I and II,
      that are membrane bound serine/threonine protein kinases. Bone morphogenetic
      proteins bind to extracellular matrix and their collaborative action on
      osteogenic cells culminates in the terminal differentiation of the osteoblast
      osteocyte continuum. Bone morphogenetic proteins are currently on the threshold
      for clinical applications.

PMID- 7641469
TI  - Endogenous lipids in matrix-induced bone morphogenesis.
AB  - Demineralized matrix was delipidized with chloroform methanol before and after
      demineralization and implanted in muscle of allogeneic rats. Because lipids are
      difficult to separate completely from bone collagen, another preparation was
      gelatinized and delipidized with either chloroform methanol or acetone or both.
      Bone matrix demineralized without delipidization induced formation of a spherical
      shaped deposit of new bone, which was remodeled to form a shell of cortical bone
      and central pool of normal hematopoietic bone marrow. When the bone was
      delipidized, only 20% to 25% was resorbed and replaced by new bone; unresorbed
      matrix failed to recalcify. Gelatinized bone matrix delipidized before
      implantation was even less well resorbed or replaced by new bone, but 12% to 44%
      of the matrix residue recalcified. The new deposits of bone were colonized by
      blood-borne bone marrow-derived stem cells and developed central pools of normal
      hematopoietic bone marrow. Recalcified residual matrix did not develop bone
      marrow. Additional investigations are required to determine whether the host bed
      adipocytes provide the phospholipids for recalcification of bone matrix. There
      was no preliminary recalcification in matrix-induced bone development, even
      though the 2 processes may occur simultaneously under specified experimental and
      pathologic conditions. Additional investigations are in progress to determine
      whether certain acetone soluble lipids may form the endogenous delivery system
      for bone morphogenetic protein and induced bone development.

PMID- 7641470
TI  - The mechanism of bone induction and bone healing by human osteosarcoma cell
      extracts.
AB  - Saos-2 cultured human osteosarcoma cells contain an extractable bone inducing
      agent that can induce heterotopic bone in the muscle of Nu/Nu mice. A
      semipurified GuHCl extract of Saos-2 cells also can promote healing and complete
      bony union in otherwise non-healing surgically induced defects of rat femur.
      Northern blot analyses indicate expression of mRNAs for bone morphogenetic
      proteins (BMP)-1, 2, 3, 4, 6 and transforming growth factor beta (TGF beta) in
      Saos-2 cells, and BMP-2, 3, 4, 5, 7 and TGF beta in nonosteoinductive U20S human
      osteosarcoma cells. Saos-2 cells exceeded U20S cells in expression levels of BMP
      1, 3, 4 and TGF beta, whereas U20S cells expressed higher levels of BMP-2, 6 and
      also expressed trace amounts of BMP-5 and 7 not seen in Saos-2 cells. The authors
      hypothesize that Saos-2 cells contain an optimal admixture of known bone growth
      factors plus possible other unknown components that, acting alone or in
      combination with bone morphogenetic protein and/or TGF beta, can induce bone.
      Although bone inducing agent-induced heterotopic bones have half lives of only a
      few weeks, the reparative bone induced by bone inducing agent in femoral defects
      gives every indication of being permanent and self-sustaining. This suggests a
      fundamental difference between heterotopic and orthotopic osteoprogenitor cells
      with those involved in orthotopic bone repair more closely resembling the
      committed or determined osteoprogenitor cells of marrow as described by
      Friedenstein.

PMID- 7641471
TI  - Posterior capsulorrhaphy in total shoulder arthroplasty. A case report.
AB  - The management of intraoperative posterior instability during total shoulder
      arthroplasty includes soft tissue balancing, reduction of humeral component
      retroversion, and augmentation of posterior glenoid defects. Severe instability
      caused by incompetence of the posterior capsule may require plication of the
      capsular remnant or a posterior muscle to the glenoid or proximal humerus. A
      technique of posterior capsulorrhaphy to the proximal humerus is described that
      does not require a separate surgical approach. By restoring stability, early
      range of motion exercises can be instituted, eliminating the need for
      postoperative immobilization. Posterior stability should be assessed during all
      total shoulder arthroplasties.

PMID- 7641472
TI  - Arthroscopic surgery of the elbow. Therapeutic benefits and hazards.
AB  - In this study, 22 patients were reviewed who underwent arthroscopic surgery of
      the elbow mainly for loose bodies or osteochondrotic lesions. Of these, 12
      patients rated the result as good or excellent, 4 had slight improvement, and 6
      were not satisfied. The average score (Hospital of Special Surgery scoring
      system; maximum 100 points) was raised from 70 points to 87 points after surgery.
      Patients with loose bodies in the elbow and no severe damage of the articular
      cartilage benefitted most. The results in patients with marked degenerative
      changes differed considerably.

PMID- 7641473
TI  - Cementless femoral components should be made from cobalt chrome.
AB  - Before 1982, the authors performed 177 primary total hip arthroplasties using a
      single-sized, extensively porous-coated cobalt-chrome femoral prosthesis. The
      current status of 122 of these arthroplasties is known. Two femoral prostheses
      have been revised for late symptomatic loosening, 2 for stem fracture, and 1 for
      infection. From 1982 to 1984, 227 primary arthroplasties were performed using the
      same stem in multiple sizes. Of these cases, 171 are available for followup. One
      stem (0.6%) has been revised for symptomatic loosening. Large osteolytic femoral
      lesions (average size, 8.1 cm2) developed in 3 patients, associated with an
      unusually large amount of polyethylene wear of their acetabular components. These
      patients have been treated by exchange of the polyethylene liner within the
      porous-coated acetabular component and allografting of the osteolytic lesions.
      The femoral components were not exchanged because osteolysis had not eroded the
      integrity of the supporting bone-implant interface to a point where loosening
      occurred. Before 1987, 193 patients with loose femoral components were treated
      with revision total hip arthroplasty, also using an extensively porous-coated
      cobalt-chrome femoral stem of similar design. Ten (5.7%) patients have required
      rerevision of the femoral prosthesis. Six of these 10 rerevisions were performed
      because of symptomatic loosening. Ninety-three percent of the patients in the
      primary series had relief of their preoperative pain and have improved functional
      ability; 94.2% are satisfied with their results. In the revision series, 89.1% of
      the patients are free of pain and function better than preoperatively, and 89.6%
      are fully satisfied with their results.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7641474
TI  - The effect of heterotopic bone formation on prosthetic loosening after total hip
      replacement.
AB  - Seven hundred thirty-two total hip replacements performed from 1970 to 1980 were
      evaluated for the degree of heterotopic bone formation postoperatively and its
      effect on long-term mechanical loosening. There were 231 Charnley total hip
      replacements, of which 152 had no heterotopic bone formation, 58 had Grade 1
      formation, and 21 had Grade 2 or 3 formation. Among the 123 Mueller total hip
      replacements, 98 had no heterotopic bone formation, 19 had Grade 1 formation, and
      6 had Grade 2 or 3 formation. For the 378 T-28 total hip replacements, there were
      305 with no heterotopic bone formation, 59 with Grade 1 formation, and 14 with
      Grade 2 or 3 formation. Survival analyses using the definition of failure as
      loosening, fracture, or revision of the acetabulum or femoral components were
      constructed. There was no correlation between mechanical loosening, fracture, or
      revision of the total hip replacement and any degree of heterotopic bone
      formation.

PMID- 7641475
TI  - Osteoarthrosis and late growth.
AB  - To examine the hypothesis that late growth of bone may occur, pelvic radiographs
      taken during 1990 to 1992 of patients born between 1901 and 1972 were studied.
      All radiographs were taken using the same equipment with constant exposure
      techniques. Films showing osteoarthrosis (obviously decreased joint space) or hip
      fracture were discarded. The remaining films of 116 women and 100 men divided
      into 3 age groups (18-39 years old, 40-59 years old, and > 60 years old) were
      measured. With a millimeter ruler and a circle template, the center and 5 radii
      of each femoral head, the width of the acetabulum, and the pelvic diameters, the
      femoral neck, and the height of the superior joint space were determined. Most of
      the measurements increased significantly with age, including those of the femoral
      head, the acetabulum, the femoral neck in women, and the pelvic diameters. The
      increase in superior joint space (the combined heights of the cartilage of the
      femoral head and acetabulum) with age was not significant, but in men between 50
      and 70 years old there were cartilage measurements that were higher than in other
      age groups, and in women > 80 years of age there were significantly more single
      high values. The results are discussed against the background that growth of bone
      and of cartilage can hypothetically cause injuries of the cartilage.

PMID- 7641476
TI  - Relationship between severity of gonarthrosis and cardiovascular fitness.
AB  - Cardiovascular fitness was assessed in 3 groups of patients having varying
      severity of gonarthrosis. Group I consisted of 16 patients with severe knee
      symptoms scheduled for total knee arthroplasty. Group II included 17 patients
      with medically treated osteoarthrosis who were not considered surgical candidates
      because knee symptoms were not severe. Group III consisted of 14 healthy control
      patients with no lower extremity arthritis. All patients were evaluated with
      Hospital for Special Surgery knee scores, Arthritis Impact Measurement Scale
      questionnaires, and a cardiopulmonary exercise test using semi-upright bicycle
      ergometry. All patients achieved anaerobic threshold during exercise. Mean (+/-
      standard deviation) maximum oxygen consumption (VO2) at peak exercise was 13.9 +/
      3.3 for Group I, 16.2 +/- 4.1 for Group II, and 21.5 +/- 3.9 for Group III. Mean
      (+/- standard deviation) Hospital for Special Surgery score was 55 +/- 7 for
      Group I, 70 +/- 14 for Group II, and 100 +/- 1 for Group III. Lower Hospital for
      Special Surgery score was associated with lower VO2 at peak exercise, suggesting
      that inactivity secondary to more severe arthritic symptoms can result in
      cardiovascular deconditioning. The association between severity of gonarthrosis
      and cardiovascular deconditioning supports the concept that a regular exercise
      program should be recommended for patients with arthritis. Also, for patients who
      are surgical candidates, the practice of delaying total knee arthroplasty may be
      associated with worsening cardiovascular fitness, particularly when physical
      activity becomes more limited. The expected longevity of implant function as well
      as the effect of continued arthritic symptoms on cardiovascular fitness should be
      considered when determining the optimal time for a patient to undergo total knee
      arthroplasty.

PMID- 7641477
TI  - Squatting following total knee arthroplasty.
AB  - This prospective study was performed to investigate whether postoperative
      alternate flexion and extension splinting (daily change in position of
      immobilization by splinting) was useful in restoring full range of motion (ROM)
      after total knee arthroplasty as compared with continuous passive motion. The
      alternate flexion and extension splinting group and the continuous passive motion
      group were each composed of 34 knees. Final ROM was measured at an average of 3.5
      years postoperatively. Squatting was possible in 31 knees (45.6%) of the
      alternate flexion and extension splinting group. The postoperative ROM of the
      osteoarthritic knees (131.8 degrees +/- 12.3 degrees) was significantly greater
      than that of the rheumatoid knees (121.9 degrees +/- 22.4 degrees) (p < 0.05).
      The postoperative ROM of the alternate flexion and extension splinting group
      (135.1 degrees +/- 11.9 degrees) also was significantly greater than that of the
      continuous passive motion group (120.0 degrees +/- 19.7 degrees) (p < 0.01).
      There was no statistically significant relationship between the posterior slope
      of tibial cutting and the postoperative ROM. It is suggested that alternate
      flexion and extension splinting is effective in restoring full ROM after total
      knee arthroplasty.

PMID- 7641478
TI  - Occult osseous lesions associated with anterior cruciate ligament tears.
AB  - Occult osseous lesions occurring with anterior cruciate ligament tears have been
      described only recently. Twenty patients with complete anterior cruciate ligament
      disruptions and evidence of occult osseous lesions on their preoperative magnetic
      resonance (MR) images were evaluated retrospectively at 24- to 73-months'
      followup to document the natural history and long-term effects of the lesions.
      Thirty-seven initial osseous signal abnormalities were documented on the MR
      images of 20 patients. All 20 patients had lesions in the posterolateral tibial
      plateau, and 13 had additional lesions in the lateral femoral condyle. Twenty
      four of the 37 osseous lesions appeared resolved on followup MR images, and 13
      had become sclerotic. Lesions of the lateral tibial plateau were especially
      likely to be sclerotic at followup. This study reaffirms the specificity of bone
      signal abnormalities of the posterolateral tibial plateau and lateral femoral
      condyle in association with complete anterior cruciate ligament tears. The data
      indicate that a proportion of anterior cruciate ligament patients will incur
      progressive articular cartilage abnormalities, although case-by-case predictions
      based on initial MR images would be unreliable.

PMID- 7641480
TI  - Knee deformities in multiple hereditary exostoses. A longitudinal radiographic
      study.
AB  - For a mean period of 7.8 years, the morphology of knee deformity and its annual
      changes in 8 patients (16 knees; mean age at the initial examination, 8.4 years)
      with multiple hereditary exostoses were evaluated radiographically. Knee
      deformity developed during the growth spurt period. Genu valgum with a
      femorotibial angle that decreased more than 2 standard deviations from the mean
      of age-matched normal children was observed in 6 of the 16 knees. In 3 of these 6
      knees, recurrent dislocation of the patella was observed. Angulation of the femur
      varied among the knees, but the tibia showed valgus angulation in the proximal
      metaphysis in all knees. Thus, knee deformity in patients with multiple
      hereditary exostoses was primarily genu valgum caused by valgus angulation of the
      tibia.

PMID- 7641479
TI  - Local control of bone formation by osteoblasts.
AB  - Although bone formation traditionally has been difficult to study in vitro,
      recent improvements in cell culture techniques have made it possible to study
      primary cultures of fetal rat calvarial osteoblasts, and to examine specific gene
      events associated with osteoblast proliferation, differentiation, and
      mineralization of extracellular matrix to form bone nodules. Results of studies
      show that extracellular matrix proteins such as Type I collagen and osteocalcin
      are expressed. Also expressed are growth regulatory factors such as the bone
      morphogenetic proteins, which are presumably secreted and stored in the bone
      matrix or involved in additional osteoblast differentiation in an
      autocrine/paracrine role. The bone matrix is 1 source of these growth regulatory
      factors for bone formation; another is those animal and human tumors associated
      with osteoblastic metastases. In some of these tumors, an extended form of basic
      fibroblast growth factor has been identified, and various bone morphogenetic
      proteins have been found in others.

PMID- 7641481
TI  - Operative treatment of nonunion of surgical neck fractures of the humerus.
AB  - Seventeen patients who had undergone operative treatment for painful nonunion of
      a surgical neck fracture of the proximal humerus were evaluated an average of 6.3
      years (range, 2-11 years) from the time of surgery to determine clinical and
      radiographic outcome. Ten patients underwent open reduction and internal fixation
      with tension band wiring and Rush rods, and 7 underwent proximal humeral
      hemiarthroplasty. The average age of the patients was 60 years old. After
      surgery, pain, function, and range of motion improved for both groups. University
      of California Los Angeles scores improved from an average of 4.4 to 22 points in
      the internal fixation group and from 4.8 to 21.4 in the hemiarthroplasty group.
      All 17 patients were eventually able to perform activities of daily living
      independently. No patient in either group was able to return to his or her
      preinjury level of work. Nonunion persisted in 2 patients who had undergone
      internal fixation, and avascular necrosis developed in 2 others. Eight of 10
      patients in the internal fixation group required removal of the Rush rods for
      treatment of symptomatic mechanical impingement. Painful nonunion of a surgical
      neck fracture of the proximal humerus is a difficult problem to manage
      operatively. Pain relief and functional improvement was similar in patients who
      underwent either procedure. However, 11 of 17 patients had fair or poor ultimate
      outcomes.

PMID- 7641482
TI  - Correct placement of the screw or nail in trochanteric fractures. Effect of the
      initial placement in the migration.
AB  - This is a prospective study of 106 patients with 37 stable and 69 unstable
      trochanteric fractures treated with 2 different implants: a sliding screw-plate
      and a triflanged nail-plate. The fractures were classified according to Jensen's
      modification of Evans classification. The parameter migration was compared
      between the 2 implants and for the various areas of placement of the screw or
      nail within the femoral head. For stable fractures, the migration observed was
      independent of the area of implant placement or the type of implant used. For
      unstable fractures, central placement of the sliding screw resulted in a
      decreased mean value of migration. When the nail was used, the mean values of
      migration observed were independent of the areas of placement within the femoral
      head. In cases of central placement, the sliding screw appeared to be superior to
      the triflanged nail.

PMID- 7641483
TI  - Septic sacroiliitis.
AB  - The authors treated 31 patients with septic arthritis of the sacroiliac joint (14
      patients with tuberculosis, 7 acute staphylococcal, 6 gonococcal, and 4 typhoid).
      The clinical presentation was vague and nonspecific, but most patients reported
      buttock pain, low back pain and difficulty walking. In 28 patients, the diagnosis
      was established after clinical examination, bone scans, hematologic
      investigations, and blood cultures. The diagnosis was established through
      arthrocentesis of the sacroiliac joint in 9 patients. In 3 patients, there was a
      delay in diagnosis. Twenty-nine patients improved on a conservative regimen of
      bed rest and antibiotics. Two patients required open drainage because of a large
      buttock abscess that was secondary to tuberculosis sarcoiliitis.

PMID- 7641484
TI  - Severe symptomatic osteopenia in a man with pigmented micronodular adrenal
      hyperplasia.
AB  - The authors describe the unusual case of a 52-year-old man with Cushing's
      syndrome caused by bilateral pigmented micronodular adrenal hyperplasia. The only
      features of hypercortisolism were hypertension and severe symptomatic osteopenia
      with vertebral, rib, and scapular fractures. Four years after bilateral
      adrenalectomy, the bone density had increased slightly, but the patient remained
      osteopenic and continued to have vertebral compression fractures. This case
      report emphasizes the importance of an indepth search for secondary causes of
      osteoporosis, including evaluation of adrenal function in patients who have
      unexplained osteoporosis. Early diagnosis and treatment is imperative to prevent
      severe bone loss and associated skeletal morbidity.

PMID- 7641485
TI  - Ultrastructural observations on fibril profiles in normal and degenerative human
      articular cartilage.
AB  - Ultrastructural changes in collagen fibril morphology in human osteoarthritis
      have not been critically analyzed. In this study, fibril profiles in healthy and
      fibrillated articular cartilage samples obtained from specimens resected during
      prosthetic arthroplasty were examined by transmission electron microscopy.
      Collagen fibrils were deposited parallel to the articular surface in the
      tangential zone, but were aligned radially to the surface in the deeper layers.
      In the 3 zones studied, fibril volume density was similar despite interzonal
      variation in mean fibril diameter values. The pattern of collagen deposition in
      degenerative samples correlated to some extent with the severity of surface
      fibrillation seen by light microscopy. Samples in which fibrillation was confined
      to the superficial zone contained fibril profiles similar in size and orientation
      to those seen in control samples. Where fibrillation extended to the deeper
      zones, volume density and mean fibril diameter values decreased accordingly. The
      data suggest that fibril profile differences may reflect variations in matrix
      proteoglycan levels between normal and degenerative samples.

PMID- 7641486
TI  - Contractile characteristics on electrical stimulation of muscle with multiple
      motor points. An in vivo study in rabbits.
AB  - The purpose of this study was to investigate the significance of motor points in
      muscle and to determine their role in functional electrical stimulation. The long
      head of the triceps in adult female rabbits was used as the muscle model to study
      the contractile response to electrical stimulation of 1 motor point as opposed to
      simultaneous stimulation of multiple motor points in the muscle belly. The
      contractile response was studied with gradually increasing voltage amplitude and
      with or without added loads. Simultaneous stimulation of multiple motor points
      gave a consistently greater range of elbow extension when compared with
      stimulation of individual motor points. At low-voltage values, simultaneous
      stimulation of multiple motor points gave excursions obtainable only with high
      voltages on a single motor point. This pattern was observed with and without
      loads. These findings indicate that for optimal control of muscle contraction in
      functional electrical stimulation, electrodes may need to be inserted into
      multiple motor points for a given muscle. Stimulation for maximal muscle function
      then may be possible in the optimal low-voltage range without relying on
      spillover effect of high voltages. Nerve, muscle, and electrode damage also may
      be avoided.

PMID- 7641487
TI  - Tension characteristics of the iliotibial tract and role of its superficial
      layer.
AB  - Change in tension along the iliotibial tract by sectioning its superficial layer
      was analyzed using 5 fresh whole cadavers, and the role of the superficial layer
      was investigated. Tibial attachment of the iliotibial tract (Gerdy's tubercle)
      was detached and pulled gradually in a distal direction with respect to the
      femur. Tension along the iliotibial tract by the distal movement of Gerdy's
      tubercle (stretching the iliotibial tract) was measured first when the whole
      iliotibial tract was intact, and then when the superficial layer was sectioned at
      different levels. When the superficial layer was sectioned above the greater
      trochanter, no significant change in tension was observed from that observed when
      the whole iliotibial tract was intact. When the superficial layer was sectioned
      at the middle of the thigh, the tension at Gerdy's tubercle was significantly
      reduced. It was concluded that not only Kaplan's fibers, those attached to the
      distal end of the femur and Gerdy's tubercle, but also the superficial layer of
      the iliotibial tract had an important role in producing tension at Gerdy's
      tubercle.

PMID- 7641488
TI  - Real-time calcium response of cultured bone cells to fluid flow.
AB  - Using a parallel-plate flow chamber and fura-2 fluorescence microscopy,
      intracellular calcium was measured cell by cell in preconfluent primary culture
      rat calvarial bone cells to 18, 35, and 70 dynes/cm2 of fluid-induced shear
      stress. A heterogeneous response with respect to peak amplitude and latency was
      observed for the culture, with an overriding dose-dependent relationship between
      the mean peak amplitude of response and shear-stress magnitude. A dose dependence
      was observed between the number of responsive cells (responding > 50% over basal
      levels) and shear-stress magnitude. Not all cells could be restimulated by
      repeated exposure to flow. The observed cell response appears to be independent
      of whether cells are clustered together or isolated. Substratum stretch,
      hydrostatic pressure, and fluid shear stress have been shown in the literature to
      increase inositol phosphate (IP3) in bone cells, with IP3 causing the release of
      calcium from intracellular stores such as the endoplasmic reticulum. Therefore, a
      6-fold inhibitory effect observed when calcium release from stores was blocked
      with 8-(n,N-diethylamino)octyl 1-3,4,5-atrimethoxybenzoate hydrochloride
      implicates an IP3 biochemical pathway mediating the fluid flow response in bone
      cells.

PMID- 7641489
TI  - In vitro effects of growth factors and dexamethasone on rat marrow stromal cells.
AB  - Bone marrow contains multipotential stromal stem cells that can differentiate
      into fibroblastic, osteogenic, adipocytic, and other cell lines. There is
      evidence for a considerable degree of plasticity in the differentiation of these
      different marrow stromal lines. Additional studies have been undertaken
      investigating the effects of basic fibroblastic growth factor (bFGF),
      transforming growth factor beta (TGF beta), and dexamethasone on the
      proliferation and differentiation of rat marrow stromal cells in in vitro
      cultures. Cell proliferation was stimulated by bFGF and inhibited by
      dexamethasone and TGF beta. Alkaline phosphatase activity was stimulated by TGF
      beta and dexamethasone, whereas the expression of the enzyme was inhibited by
      bFGF. Adipogenesis was induced in cultures containing dexamethasone, but this was
      depressed by the presence of TGF beta. These observations support the authors'
      previous hypothesis that there may be an inverse relationship between the
      differentiation of osteogenic and adipocytic cell lines. The results are relevant
      to osteoporosis and the aging skeleton, where excess marrow fat is a common
      feature, and have implications for the pathology of bone and marrow.

PMID- 7641490
TI  - Antiinflammatory drug effects on bone repair and remodeling in rabbits.
AB  - Ketorolac and methylprednisolone effects on bone repair were studied.
      Demineralized bone matrix was used to graft the defects of rabbits' ulnae. Twenty
      seven rabbits were divided into 4 groups: Group A (control group; no drug
      treatment), Group B (treated with ketorolac 2 mg/kg body weight daily), Group C
      (treated with ketorolac 4 mg/kg body weight daily), and Group D (treated with
      methylprednisolone 1 mg/kg body weight weekly). Drug treatment was continued for
      6 weeks. The biomechanical results indicated methylprednisolone significantly
      deteriorated the mechanical properties of the grafted ulnae and the contralateral
      intact ulnae, although the effects were more pronounced in the grafted side. In
      Group B, there was minimum effect of ketorolac on the bone properties. In Group
      C, ketorolac significantly decreased the torsional stiffness and energy
      absorption of the grafted ulnae and also decreased the maximum torque in the
      intact and the grafted bones. It was concluded that the inhibitory effect of
      ketorolac on bone repair was dose dependent. In comparing the effects of
      ketorolac and methylprednisolone, the latter is more pronounced on torsional
      stiffness, but the effects on maximum torque and energy absorption were similar
      to ketorolac. The mechanism of the effects of ketorolac needs additional
      investigation.

PMID- 7641491
TI  - In vitro chemosensitivity assay for human osteosarcoma using tumor xenografts.
AB  - The authors have established an in vitro chemosensitivity assay for human
      osteosarcoma. To overcome the difficulty of maintaining primary osteosarcoma
      cells in culture, biopsy or surgical specimens were transplanted directly into
      athymic nude mice and early generation xenografts were used for in vitro
      scintillation assay. These xenografts enabled a large number of viable tumor
      cells to be obtained even from small biopsy specimens. As a result, this system
      afforded a workable assay in 21 (62%) of 34 osteosarcomas tested and enabled the
      assay of numerous drugs at 4 different concentrations. Reproducibility of the
      assay can be checked by using serially transplanted xenografts. Retrospectively,
      the in vitro results were compared with the histologic response of the resected
      tumor in 18 patients who had received preoperative chemotherapy. The true
      positive rate, true negative rate, and predictive accuracy were 40%, 100%, and
      66.7%, respectively. The authors suggest that this system provides a valid tool
      to determine which drugs are ineffective in individual osteosarcoma patients and
      thus may allow more efficient therapy.

PMID- 7641492
TI  - A tribute to Mr. "BMP". Marshall Urist.

PMID- 7641493
TI  - Knee pain in an 18-year-old man.

PMID- 7641494
TI  - Chopart amputation with percutaneous heel cord lengthening.

PMID- 7641495
TI  - Cell population kinetics of an osteogenic tissue. I. 1963.

PMID- 7641496
TI  - The role of prostaglandins in the regulation of bone metabolism.
AB  - Prostaglandins are likely to play an important role in the physiologic and
      pathologic responses of skeletal tissue. They are potent agonists that can
      stimulate and inhibit bone resorption and formation. In vivo, the major effect of
      exogenous prostaglandins, particularly prostaglandin E2, is to stimulate
      resorption and formation. These effects appear to involve replication and
      differentiation of osteoclast and osteoblast precursors, and to be mediated at
      least in part by cyclic 3' 5' adenosine monophosphate. Prostaglandins can inhibit
      the activity of isolated osteoclasts, probably also by a cyclic 3' 5' adenosine
      monophosphate-mediated mechanism. Inhibition of collagen synthesis can be seen in
      cell and organ cultures and appears to be caused by a receptor selective for
      prostaglandins of the F series and to involve activation of protein kinase C.
      Prostaglandin production by bone cells is regulated highly by mechanical forces,
      cytokines, growth factors, and systemic hormones. Prostaglandins also can amplify
      their own production. Regulation is associated with marked changes in the newly
      described "inducible" prostaglandin G/H synthase with less effect on the
      constitutive enzyme. Prostaglandins also may play a role in postmenopausal bone
      loss because estrogen deficiency, which increases bone turnover, can increase
      prostaglandin production in bone.

PMID- 7641497
TI  - Is collagenase (matrix metalloproteinase-1) necessary for bone and other
      connective tissue remodeling?
AB  - In physiologic remodeling of bone and other connective tissues, proteinases such
      as the matrix metalloproteinases (MMPs) which can cleave Type I collagen play a
      critical role. In bone, MMP-1 is secreted by stromal fibroblasts, osteoblasts,
      and osteoclasts. Only the collagenases (MMP-1 and MMP-8) cleave native
      undenatured collagen at neutral pH. The cleavage is site specific at a single
      locus in the alpha 1(I) chain between Gly775/Ile776. The authors have altered the
      amino acid sequences around the collagenase cleavage site by site-directed
      mutagenesis of the murine Col1a-I gene, introducing Pro for Gln774, Pro for
      Ala777, and Met for Ile776. The mutant Col1a-I gene has been expressed in Mov13
      fibroblasts, and secreted Type I collagen molecules have been found to be
      resistant to cleavage at Gly775/Ile776 by MMP-1 or MMP-8. This subtle mutation
      was introduced recently into the endogenous Col1a-I gene by homologous
      recombination in embryonic stem cells to determine the role of collagenase in
      vivo. Chimaeric mice derived from blastocysts injected with these embryonic stem
      cells transmitted the mutant Col1a-I gene to their offspring. Surprisingly,
      homozygous mutant mice reproduce and appear to develop normally. The mechanisms
      of collagen resorption in remodeling of bone and soft tissues in these mice are
      being examined currently. Information should be derived that will be useful in
      interpreting human disorders characterized by increased collagen deposition, such
      as osteopetrosis and dermal fibrosis.

PMID- 7641498
TI  - The plasminogen activator inhibitor system in bone cell function.
AB  - The plasminogen activator (PA)/plasmin pathway has been implicated in a variety
      of physiologic and pathologic processes that require tissue remodeling and cell
      motility. The pathway is highly regulated and results in the generation of the
      broad spectrum serine protease, plasmin, from the zymogen plasminogen. Urokinase
      type plasminogen activator (uPA) and tissue-type plasminogen activator (tPA) are
      produced by osteoblasts, as are the specific inhibitor plasminogen activator
      inhibitor-1 (PAI-1) and a cellular receptor for uPA. Little is known about
      regulation of the receptor, but the other 3 components of the pathway are
      regulated differentially by various osteotropic hormones and local factors.
      Several roles have been proposed for this pathway in bone. These involve
      proteolytic activation of procollagenase and latent growth factors, such as
      transforming growth factor beta (TGF beta) and insulin-like growth factor (IGF),
      as well as cell motility as a result of pericellular proteolysis. The roles of
      this pathway in bone remodeling may not be confined to proteolytic events,
      because uPA has been reported to act as a mitogen on osteoblast-like cells. This
      effect is independent of proteolytic activity but requires the growth factor
      domain of uPA to bind to uPA cellular receptors. If the plasminogen
      activator/plasmin pathway encompasses these roles, it would serve to couple
      formation and resorption of bone in a highly regulated manner.

PMID- 7641499
TI  - Regulatory role of osteogenic growth peptide in proliferation, osteogenesis, and
      hemopoiesis.
AB  - Bone marrow regeneration after injury is preceded by local and systemic
      osteogenic reactions. Recently, an osteogenic growth peptide was characterized in
      the regenerating marrow. The osteogenic growth peptide also is abundant in normal
      serum where it is markedly and transiently increased after marrow injury. This
      increase and the osteogenic growth peptide-induced stimulation of bone formation
      in vivo suggest a role for this peptide in mediating the systemic osteogenic
      response. In vitro, the osteogenic growth peptide is an autocrine mitogen for
      osteoblastic and fibroblastic cells. It also stimulates alkaline phosphatase
      activity and matrix mineralization. The serum osteogenic growth peptide is
      downregulated in osteoporotic ovariectomized mice. The osteogenic growth peptide
      levels as well as the bone loss, tetracycline uptake, and serum osteocalcin are
      reversed by exogenously administered osteogenic growth peptide. In normal mice,
      the osteogenic growth peptide increases white blood cell counts and total femoral
      bone marrow cellularity. These increases include all the hemopoietic lineages.
      When given to mice for 1 week before ablative radiotherapy and bone marrow
      transplantation, synthetic osteogenic growth peptide stimulates the bone marrow
      transplant engraftment; optimal osteogenic growth peptide doses doubled the
      survival rate. These data indicate that osteogenic growth peptide has an
      important role in the pathogenesis and treatment of systemic bone loss and
      provide a basis for further development of an antiosteoporotic osteogenic growth
      peptide therapy. It is suggested also that the osteogenic growth peptide promotes
      hemopoiesis secondary to the stimulation of the stromal (particularly osseous)
      microenvironment.

PMID- 7641500
TI  - Age-related bone loss. A hypothesis and initial assessment in mice.
AB  - The osteopenia associated with advanced age appears to be a universal phenomenon
      in humans and animals, but the mechanisms by which it occurs are understood
      incompletely. However, the explanation must lie in an absolute or relative
      diminution in the level of osteoblastic bone-forming activity when compared with
      osteoclastic bone-resorbing activity. The authors postulated that with old age
      there would be a reduction in the number or function or both of osteoblastic stem
      cells that could account for part of the diminution in bone formation. They
      further postulated that there would be either no change or an increase in
      osteoclastic potential and bone resorption. To test these concepts, bone marrow
      cells were isolated from 4- to 6-month-old or 24-month-old mice and cultured in
      vitro under a variety of circumstances that permitted an assessment of the
      stromal osteogenic cells and marrow hemopoietic progenitor cells belonging to the
      monocyte and osteoclast series. These data show a marked reduction in the number
      and in vitro activity of stromal osteogenic cells from old animals. There is an
      increase in old mice in the number of marrow cells capable of forming osteoclasts
      in coculture and responsive to the growth factors believed operational in the
      monocyte and osteoclast series. The authors now are exploring the hypothesis that
      an age-related diminution in transforming growth factor-beta levels is
      responsible for these changes in progenitor cell levels in marrow and their
      functional status as expressed in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7641502
TI  - Injectable bone marrow preparations to stimulate osteogenic repair.
AB  - The great versatility of bone marrow transplants based on stem cell activity has
      been demonstrated successfully for a variety of previously untreatable
      hemopoietic conditions. Autologous bone marrow delivered by percutaneous
      injection or by direct transplant as a composite graft also has proven effective
      for osteogenic stimulation in a series of 100 skeletal healing problems,
      including delayed unions and nonunions of fractures, arthrodeses, and bone
      defects. The efficiency of marrow to form bone can be increased by a number of
      methods, including differential centrifugation and composite grafts of marrow
      with demineralized bone matrix and other carriers or stimulatory factors.

PMID- 7641501
TI  - Expression and regulation of vascular endothelial growth factor in osteoblasts.
AB  - Bone formation is linked closely to angiogenesis. Because prostaglandin E2 (PGE2)
      is a potent stimulator of bone formation, its effects were evaluated on vascular
      endothelial growth factor, a secreted endothelial cell-specific mitogen, and a
      potent angiogenic protein. Prostaglandin E2 increased vascular endothelial growth
      factor protein in conditioned media of osteoblastic RCT-3 cells within 3 hours.
      Prostaglandin E2 also increased the steady-state levels of vascular endothelial
      growth factor mRNA in a dose-dependent manner. The increased expression of
      vascular endothelial growth factor mRNA produced by PGE2 was rapid (maximal at 1
      hour) and was enhanced by the protein synthesis inhibitor cycloheximide (5
      micrograms/ml). The increase in vascular endothelial growth factor mRNA by PGE2
      was inhibited strongly by pretreatment for 3 hours with dexamethasone (10(-7) M).
      Stimulation of vascular endothelial growth factor by PGE2 and its suppression by
      dexamethasone implicate the involvement of vascular endothelial growth factor in
      bone metabolism.

PMID- 7641503
TI  - Extracellular adenosine triphosphate. A shock to hemopoietic cells.
AB  - Many or perhaps all cell types in the body possess extracellular binding sites
      for nucleosides and nucleotides, the purinoceptors. The binding sites that favor
      adenosine triphosphate (ATP) have been classified as P2-purinoceptors. One
      subclass of the P2-purinoceptors is the P2z-purinoceptor that mediates the
      permeabilizing effect of ATP4- (the fully ionized form of adenosine
      triphosphate). In the presence of millimolar concentrations of ATP4-, this
      receptor, which was found on all cells of hemopoietic origin but not on cells of
      stromal origin, renders the sensitive cells permeable for molecules up to 1 kD.
      This property has been used to eliminate cells of hemopoietic origin from mixed
      populations. Skeletal- and blood-forming tissues have a complex cellular
      composition of predominantly stromal and hemopoietic cells. The 2 cell types
      influence each others' formation, differentiation, and activities in a largely
      unclarified manner. Rigorous separation would help the study of the properties
      and potencies of the 2 cell types and their mutual interactions. A short
      treatment of cell populations isolated from bone, bone marrow, or cartilage with
      2 mM adenosine triphosphate and 1 mM of cytotoxic, but not permeant, potassium
      thiocyanate obliterates all cells of hemopoietic origin, including macrophages,
      osteoclasts, and their progenitors from these populations.

PMID- 7641504
TI  - Direct effect of calcitriol on the regulation of parathyroid hormone secretion in
      a case of pseudo-hypoparathyroidism (a 24-month follow-up study).
AB  - The diagnosis of pseudohypoparathyroidism with osteitis fibrosa was made in a 51
      year-old woman on the basis of hypocalcaemia, elevated plasma PTH (1-84) and
      blunted cAMP response to hPTH infusion. Radiologically, widespread signs of
      hyperparathyroidism were observed and quantitative histomorphometry confirmed the
      increased bone cellular turnover. Treatment with calcitriol (1,25
      dihydroxyvitamin D3) induced a dramatic improvement of bone lesions. During
      treatment PTH (1-84) normalized with high dosage of calcitriol in spite of low or
      subnormal levels of serum calcium, and subsequently increased for each reduction
      of calcitriol dosage despite normal calcium levels. Our observations support a
      major and direct effect of 1,25 dihydroxyvitamin D3 on the regulation of
      parathyroid secretion of parathyroids glands.

PMID- 7641505
TI  - Serum levels of soluble forms of T cell activation antigens CD27 and CD25 in
      systemic lupus erythematosus in relation with lymphocytes count and disease
      course.
AB  - Systemic lupus erythematosus (SLE) patients are characterized by a low lymphocyte
      count, which is considered a specific disease marker and is related to disease
      activity. The membrane bound molecules CD25 and CD27 are expressed and released
      in a soluble CD25 (sCD25) and soluble CD27 (sCD27) form by activation of
      predominantly T cells. In previous studies it was claimed that sCD25 as well
      sCD27 might be used as parameters for activation of the immune system; a
      correlation between the sCD25 profile with the disease course in SLE patients was
      also shown. To assess the relationship between lymphocyte count and these T cell
      activation markers, we performed a cross-sectional and a longitudinal study. In
      the longitudinal study three SLE patients who were known for a long time at our
      outpatient clinic were studied. Both T cell markers strongly correlated with each
      other and formed a reflection of the disease course. In all 7 periods of
      exacerbation, which we observed in the 3 investigated patients, both levels
      increased preceding this period; however, no correlation was found with the
      lymphocyte count. In the cross sectional study of 69 patients with SLE, sCD25 and
      sCD27 levels were correlated with defined disease manifestations; sCD25 was
      elevated in all periods of increased disease activity. The same holds true for
      sCD27, with the exception of patients with nephritis in which the highest levels
      were observed. Both profiles of sCD25 and sCD27 were strongly correlated during
      the whole disease course. Our data prove that in the pathogenesis of SLE an
      active recruitement of unprimed and primed T cells takes place.

PMID- 7641506
TI  - CT and MRI evaluation of tenosynovitis of the rheumatoid hindfoot.
AB  - Thirty-nine patients with rheumatoid arthritis who had presented with tarsitis
      before, were investigated at the level of the rearfoot. The first 17 patients had
      CT with previous tenography when it was possible; the following 22 patients had
      MRI with gadolinium injection. Tendon involvement appeared in 52.9% of the cases
      on CT, and in 90% of the feet on MRI; therefore, in case of clinical or
      radiological signs of tarsitis, it appears that tendon involvement must be
      suspected. With the two procedures the tibialis posterior tendon lesions were
      very predominant. In the majority of the patients (31/39), there was associated
      involvement of two or more tendons. If there is a ruptured tendon, the authors
      think that one must be cautious with surgical tendinous transfer; indeed, the
      long-term results of this surgical procedure present a strong probability of
      being compromised in rheumatoid arthritis which is a progressive disease.

PMID- 7641507
TI  - Isometric and isokinetic quadriceps strength in gonarthrosis; inter-relations
      between quadriceps strength, walking ability, radiology, subchondral bone density
      and pain.
AB  - Patients with osteoarthrosis suffer from disability and pain. We measured
      isokinetic and isometric peak torque in 20 women with gonarthrosis (GA) and in 26
      healthy controls. Relationships between muscle strength, walking and stair
      climbing time, pain level and pain disability scores as assessed by the patients
      using an extensive questionnaire, radiological changes and subchondral sclerosis
      expressed as bone mineral density (BMD, g/cm2) of the proximal tibia were
      studied. Precision errors of the torque measurements in both GA patients and
      controls were approximately 6%. In the GA patients, isokinetic and isometric
      quadriceps strength was reduced by 40 and 15% (p < 0.01) respectively, and
      walking and stair climbing time was increased by 30% (p < 0.005). Isokinetic
      strength was a better predictor of pain level and pain disability scores than
      isometric strength and radiological stage. Walking time and stair climbing time
      were not associated with quadriceps strength, pain level, pain disability scores
      or radiological changes. Subchondral BMD was not predictive of pain. The study
      suggests that quadriceps strength assessed by isokinetic dynamometry in GA is a
      reliable measurement. Isokinetic strength was pronouncedly reduced compared to
      isometric strength and was a more important predictor of pain and pain disability
      than isometric strength. These findings should be taken into consideration when
      planning exercise studies and programmes in GA.

PMID- 7641508
TI  - The CRP initial response to treatment as prognostic factor in patients with
      polymyalgia rheumatica.
AB  - To test the hypothesis that the initial response to corticosteroid treatment
      makes it possible to predict the further course of patients with polymyalgia
      rheumatica (PMR), 20 patients with PMR were prospectively given a therapeutic
      challenge with 15 mg of prednisolone (PDN) per day. The erythrocyte sedimentation
      rate (ESR), the fibrinogen and the C-reactive protein (CRP) were measured before
      and after 7 days of therapy. At the end of the challenge, the CRP had normalized
      in 11 patients (Group I), whereas it had remained elevated in 9 (Group II). The
      dose of PDN was thereafter tapered according to a strict and standard schedule
      integrating clinical and laboratory parameters, and was used as the index of
      disease control. The statistical analysis was made using a generalized linear
      model. Follow-up ranged from 8 to 60 months with a median of 38 months. With the
      PDN dose as the end point, Group I showed a significantly better course than
      Group II (p = 0.014). There were fewer adverse events due to corticosteroid
      treatment in Group I (3/11) compared to Group II (7/9). We conclude that the CRP
      initial response to the corticosteroid treatment is a prognostic factor in
      patients with PMR. Larger studies are needed to confirm these preliminary
      results.

PMID- 7641509
TI  - Air in the oesophagus: a sign of oesophageal involvement in systemic sclerosis.
AB  - An air oesophagogram, defined as a column of air involving the entire oesophagus,
      seen on a lateral chest X-ray was observed in 6 (20%) of 30 consecutive patients
      with systemic sclerosis (SSc) but in none of the controls. The presence of this
      sign was unrelated to the clinical subset of SSc and to age but was associated
      with the symptom of regurgitation.

PMID- 7641510
TI  - Evaluation of response to methotrexate by a functional index in juvenile chronic
      arthritis.
AB  - In juvenile chronic arthritis (JCA) the indices of disease activity, such as
      joint swelling, pain, tenderness, and limitation of motion, may poorly correlate
      with the degree of functional impairment. Since the improvement of functional
      capacity is one of the main objectives of treatment, we evaluated the effect of
      methotrexate (MTX) in 29 children with JCA by assessing both the articular
      indices and a functional status measure. After 6 months of therapy, 15 of the 29
      patients had a significant (> or = 50%) reduction in the number of joints with
      active arthritis and/or the articular severity score and were then judged as
      responders, while 14 did not respond to MTX. In the responder group, the median
      functional index score decreased from 17 (range: 13-27) at baseline to 13 (range:
      13-15) at 6 months (p < 0.001); the median score of the non-responder group was
      20 both at baseline and at 6 months (ranges: 14-27, and 13-36, respectively).
      These results show an improvement of functional impairment in those patients who
      respond to MTX according to the conventional indices of articular inflammation.

PMID- 7641511
TI  - Ultrasound-guided aspiration in suspected sepsis of resection arthroplasty of the
      hip joint.
AB  - The authors described 17 patients who had had resection arthroplasty of the hip
      and who were suspected of having an infection. The resection arthroplasties had
      been performed for previous infection. All the patients were studied by
      ultrasonography to detect effusion in the pseudoarticular space. Thirteen of the
      17 patients were found to have an effusion by ultrasonography. Fluid was obtained
      in 9 of the 13 patients by ultrasonographic-guided aspiration. The mean aspirated
      volume was 3 ml (range 1-25 ml). Five of the 9 aspirates proved to be septic. The
      echopattern in all but one of those five with sepsis was nonechofree. Of four
      other patients in whom it was not possible to aspirate fluid lavage of the
      pseudoarticular space one yielded a positive culture. The role of ultrasonography
      in the diagnosis and management of patients who have undergone resection
      arthroplasty of the hip and who are suspected of having an infected
      pseudoarticular space is discussed.

PMID- 7641512
TI  - The influence of sectional interval on the reliability of temporal arterial
      biopsies in polymyalgia rheumatica.
AB  - Temporal arterial biopsies from 27 patients with a clinical diagnosis of pure
      polymyalgia rheumatica (PMR) were examined using light microscopy on paraffin and
      plastic sections. The primary routine examination of the paraffin-embedded parts
      of the biopsies (biopsy length: 12.7 +/- 4.5 mm, sub-segments: 4.9 +/- 1.2 mm)
      revealed 4 positive cases, whereas the primary examination of the smaller plastic
      embedded parts showed inflammation in 6 cases (biopsy length: 2.7 +/- 1.2 mm, sub
      segments: 0.7 +/- 0.3 mm). Serial sectioning with a 50 microns interval of
      arteries which were negative primarily revealed three new positive cases in the
      paraffin-embedded material (total length: 174.0 mm), whereas sectioning the
      plastic-embedded material (total length: 52.8 mm) produced one more positive
      artery. All the new cases displayed a focal inflammatory process in atrophic,
      calcified arterial segments. The high yield of positive biopsies in the present
      material (11 of 27; 40.7%) demonstrates the diagnostic value of temporal arterial
      biopsy in PMR and the importance of a careful histologic examination. The results
      also indicate the influence of biopsy length on the yield of positive biopsies.
      The division of fixed temporal arterial biopsies into approximately 1-mm-long sub
      segments before the embedding and the further serial sectioning of those negative
      biopsies which are atrophic and/or calcified is recommended in cases of pure PMR.

PMID- 7641513
TI  - Systemic lupus erythematosus in Saudi patients.
AB  - Eighty-seven patients with systemic lupus erythematosus (SLE) were
      retrospectively studied in King Khalid University Hospital, Riyadh. There were 78
      females and 9 males (F:M ratio of 9:1). The mean age (+/- SD) at onset and at
      diagnosis were 25.3 +/- 10.5 and 28.5 +/- 10.9 years, respectively, with peak
      incidence in the 20-30 year age group. Musculoskeletal (91%), constitutional
      (76%), cutaneous (72%) and renal (63%) manifestations occurred most frequently,
      while neuropsychiatric manifestations (26%), photosensitivity (26%) and oral
      ulcers (16%) were relatively less frequent. The most common laboratory
      abnormalities included ANA (98%), anti-DNA (93%), LE cells (66%) and lymphopenia
      (70%). There were seven deaths during the study period and most of them were
      related to renal failure and complications from infections. Overall, the pattern
      of SLE observed in the series was comparable to that observed in other series
      among Caucasians.

PMID- 7641514
TI  - Factors related to change in global health after group physical therapy in
      ankylosing spondylitis.
AB  - The purpose of this study was to evaluate how improvements in global health in
      patients with ankylosing spondylitis (AS), who had received group physical
      therapy, were associated with changes in physical functioning and other outcome
      measures. Sixty-seven AS patients from 2 outpatient departments (modified New
      York criteria) received group physical therapy weekly. After 9 months we studied
      the following variables to explain changes in global health: disease duration,
      spinal mobility, fitness, functional status (SIP, HAQ and Functional Index),
      pain, stiffness, and articular and enthesis indices. Change scores were
      calculated as baseline values minus scores at 9-month follow-up. Personality
      traits (neuroticism, social inadequacy, self-esteem and health locus of control)
      and loneliness were also included as possibly explanatory variables. Patient's
      assessment of change in global health after 9 months of group physical therapy
      was self-reported on a 10 cm visual analogue scale (-5 = maximum worsening, 0 =
      no change, +5 = maximum improvement). Correlations were calculated between change
      in global health and all candidate explanatory variables. In this pre/post test
      design multiple and stepwise regression analyses were performed to study the
      relations between changes in global health and all explanatory variables. Pearson
      correlation coefficients between improved global health and the explanatory
      variables were significant for lower self-esteem (0.27) and improvements in chest
      expansion (0.31), fitness (0.32), HAQ-S (0.29), and stiffness (0.33). Regression
      analysis revealed 2 significantly explanatory steps: changes in fitness explained
      16% of total variance of changes in global health, and changes in stiffness
      contributed an additional 11%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7641515
TI  - Recurrent peritonitis with ascites as the predominant manifestation of systemic
      lupus erythematosus.
AB  - We describe a patient with abdominal pain and ascites, mesenteric lymphadenitis
      and peritoneal panniculitis. Initially her ANA was negative. The abdominal pain
      recurred again three years later and in between the two episodes she had had skin
      rash, alopecia, arthralgia, and positive Coombs' test-haemolytic anaemia. Her ANA
      became positive a few years after the initial episode.

PMID- 7641516
TI  - Spinal abnormalities similar to ankylosing spondylitis in a 58-year-old woman
      with ochronosis.
AB  - Ochronotic arthropathy (spondylosis or peripheral arthropathy) is a late
      complication of alkaptonuria. There is a tendency for HLA-B27 positive patients
      with alkaptonuria to develop ochronotic spondylosis. A 58-year-old white woman,
      presented with ochronotic spondylosis. She was HLA-B27 positive. Her family
      history was positive for alkaptonuria. Ochronotic patients with HLA-B27
      positivity develop spinal changes similar to ankylosing spondylitis (AS).

PMID- 7641517
TI  - Iliopsoas bursa of the rheumatoid hip joint. A case report and review of the
      literature.
AB  - Presented is the case of a 63-year-old woman, with a 30-year history of
      rheumatoid arthritis, whose hip was completely destroyed and accompanied with
      enlargement of the iliopsoas bursa. Preoperative diagnosis was confirmed by
      computed tomography, magnetic resonance (MR) imaging and arthrography. She was
      treated by resection of the iliopsoas bursa and total prosthetic replacement of
      the hip joint. The pathogenesis is uncertain. In the literature, enlargement of
      the iliopsoas bursa with rheumatoid arthritis, osteoarthritis, pigmented
      villonodular synovitis, and synovial chondromatosis had been reported.
      Nevertheless, a correct preoperative diagnosis of the enlargement of the
      iliopsoas bursa is very difficult. MR imaging with enhanced Gadolinium-DTPA (Gd
      DTPA) is proposed as the most useful examination for preoperative diagnosis.

PMID- 7641518
TI  - A rare case of primary skeletal muscle lymphoma: the value of octreotide
      scintigraphy.
AB  - We report a case of non-Hodgkin lymphoma presenting as a painless mass of the
      quadriceps femoris muscle that was detected by a somatostatin analogue
      (octreotide) scintigraphy. We review the few reported cases of primary muscular
      lymphoma and discuss the potential value of octreotide imaging as a new
      diagnostic tool.

PMID- 7641519
TI  - Systemic lupus erythematosus with necrotizing vasculitis and upregulated
      expression of VLA-4 antigen.
AB  - We report on a patient (S.A.), with well-defined SLE who developed a perforation
      of the ileum due to pathologically confirmed necrotizing vasculitis. No anti-DNA
      antibody was detected at the ileal perforation, and the serum complement level
      was normal. These findings raise the alternative possibility of a cell-mediated
      immune mechanism as a cause of necrotizing vasculitis. Upregulated expression and
      function of VLA-4 antigen on peripheral blood T cells were observed, suggesting
      that T cells with VLA-4 antigen may participate in the onset and/or perpetuation
      of vascular inflammation.

PMID- 7641520
TI  - Polymyositis associated with primary biliary cirrhosis.
AB  - The coexistence of polymyositis (PM) and primary biliary cirrhosis (PBC) is rare;
      only nine cases have been described in English literature. We report a case of a
      46-year-old woman presenting with these two autoimmune diseases. The diagnosis of
      PM was based on the symmetrical, proximal limb muscle weakness, elevated muscle
      enzymes and was confirmed with the electromyography and muscle biopsy. The
      diagnosis of PBC was based on the increased serum levels of alkaline phosphatase,
      gamma glutamyltransferase, IgM immunoglobulin, the presence of antimitochondrial
      antibodies and diagnostic liver biopsy.

PMID- 7641521
TI  - Prevalence of autoimmune thyroid disease (AITD) in patients with mixed connective
      tissue disease (MCTD)

PMID- 7641522
TI  - Serum interleukin-6 level in patients with systemic sclerosis: lack of
      correlation with aminoterminal propeptide of type III procollagen.

PMID- 7641523
TI  - Aseptic osteomyelitis of the ilium in the palmoplantar pustulosis.

PMID- 7641524
TI  - Infants' detection of the sound patterns of words in fluent speech.
AB  - A series of four experiments examined infants' capacities to detect repeated
      words in fluent speech. In Experiment 1, 7 1/2-month old American infants were
      familiarized with two different monosyllabic words and subsequently were
      presented with passages which either included or did not include the familiar
      target words embedded in sentences. The infants listened significantly longer to
      the passages containing the familiar target words than to passages containing
      unfamiliar words. A comparable experiment with 6-month-olds provided no
      indication that infants at this age detected the target words in the passages. In
      Experiment 3, a group of 7 1/2-month-olds was familiarized with two different non
      word targets which differed in their initial phonetic segment by only one or two
      phonetic features from words presented in two of the passages. These infants
      showed no tendency to listen significantly longer to the passages with the
      similar sounding words, suggesting that the infants may be matching rather
      detailed information about the items in the familiarization period to words in
      the test passages. Finally, Experiment 4 demonstrated that even when the 7 1/2
      month-olds were initially familiarized with target words in sentential contexts
      rather than in isolation, they still showed reliable evidence of recognizing
      these words during the test phase. Taken together, the results of these studies
      suggest that some ability to detect words in fluent speech contexts is present by
      7 1/2 months of age.

PMID- 7641525
TI  - Cataphoric devices in spoken discourse.
AB  - We propose that speakers mark key words with cataphoric devices. Cataphoric
      devices are counterparts to anaphoric devices: Just as anaphoric devices enable
      backward reference, cataphoric devices enable forward reference. And just as
      anaphoric devices mark concepts that have been mentioned before, cataphoric
      devices mark concepts that are likely to be mentioned again. We investigated two
      cataphoric devices: spoken stress and the indefinite this. Our experiments
      demonstrated three ways that concepts marked by cataphoric devices gain a
      privileged status in listeners' mental representations: Cataphoric devices
      enhance the activation of the concepts that they mark; cataphoric devices
      suppress the activation of previously mentioned concepts; and cataphoric devices
      protect the concepts that they mark from being suppressed by subsequently
      mentioned concepts.

PMID- 7641526
TI  - Pediatric tuberculosis: an update.
AB  - The incidence of tuberculous infection and disease in children has risen
      significantly over the last decade. The management of TB has become more
      complicated by the changing epidemiology of this disease and the emergence of
      resistant MTB. Many new recommendations have recently been made to address these
      issues. It is crucial that pediatricians become familiar with this disease again
      and have a good working knowledge of pediatric TB.

PMID- 7641527
TI  - Major treatment considerations for attention-deficit hyperactivity disorder.

PMID- 7641528
TI  - Healthy Child Care America campaign: you can make a difference in your community.

PMID- 7641529
TI  - Mortality in a child welfare population: implications for policy.
AB  - The mortality rate in a one-year cohort of children with child welfare status in
      Alberta, Canada, was found to be significantly elevated. Specifically, neglected
      and abused children were apt to have died violently, while handicapped children
      were more likely to have died because of disease or infirmity. The proportion of
      children dying while in care did not differ from the proportion who died after
      leaving care. Death rates were elevated only for age-categories surrounding the
      point (18 years) at which child welfare support was withdrawn.

PMID- 7641530
TI  - A more humane workplace: responding to child welfare workers' personal losses.
AB  - The personal losses of employees, such as the death of a family member, divorce,
      or serious illness, can diminish work performance and increase stress. This study
      surveyed 106 child welfare workers on the type of personal loss they experienced;
      the kinds of benefits and emotional support they received from their employing
      organization, supervisor, and coworkers; their expectations; and potential
      problem areas. Eighty-five percent of the workers endured a loss during their
      current employment. They received the most help from their coworkers, followed by
      their immediate supervisors, and then the employing organization. Those suffering
      a loss would have liked more emotional support, acknowledgment of the loss, and a
      longer leave of absence for recovery than they received.

PMID- 7641531
TI  - The resolution scrapbook as an aid in the treatment of traumatized children.
AB  - The resolution scrapbook is a therapeutic technique in which traumatized children
      complete treatment activities and compile them in the form of a scrapbook.
      Scrapbook activities facilitate children's resolution of traumatization impacts.
      Their progress through the phases of treatment becomes a lasting record for the
      children after treatment is terminated.

PMID- 7641532
TI  - Support groups for children in alternate care: a largely untapped therapeutic
      resource.
AB  - Children in alternate care often have adjustment problems that manifest in
      various aspects of their lives. Individual therapy is often assumed to be the
      desired intervention, but resources seldom permit one-to-one therapy for these
      disturbances. The authors argue that groupwork should be considered as a possible
      treatment of choice. Not only is it likely to be more economical than individual
      therapy, it has the inherent advantage of telling children in care that they are
      not alone, and that other children have similar experiences and feelings. It also
      allows them to develop their own support network. Such groups appear to have been
      underutilized in work with children in out-of-home care. This article describes
      such a group and its outcome. Various techniques were developed to achieve
      specified aims. The techniques appeared to be successful. Further work on such
      groups and more specific evaluation is called for.

PMID- 7641533
TI  - Citizen's Committee for Children of New York.

PMID- 7641534
TI  - Neoadjuvant chemotherapy for the treatment of osteosarcoma of the extremities:
      excellent response of the primary tumor to preoperative treatment with
      methotrexate, cisplatin, adriamycin, and ifosfamide. Preliminary results.
AB  - A total of 48 patients with non-metastatic osteosarcoma of the extremities were
      treated with a new neoadjuvant chemotherapy protocol which, prior to surgery,
      included the use of high dose methotrexate, cisplatin, adriamycin and ifosfamide.
      Cisplatin was administered intra-arterially, whereas the other drugs were given
      intravenously. In all of the cases response to this chemotherapy protocol was
      very good, allowing for conservative treatment in 46 out of 48 patients.
      Histological evaluation of chemotherapy response showed good (> 90%) and total
      necrosis in 87 and 54% of the cases, respectively. Drug toxicity was acceptable.
      Results were significantly better than those previously obtained in our and in
      other institutes when only three drugs were used (methotrexate, cisplatin, and
      adriamycin) in the preoperative treatment scheme. Since it has been demonstrated
      that grade of histological response to preoperative chemotherapy, and prognosis
      are closely related in osteosarcoma of the extremities treated with neoadjuvant
      chemotherapy, in addition to allowing for the use of conservative surgery in the
      majority of cases, this new protocol may also lead to a significant increase in
      the patient cure rate.

PMID- 7641535
TI  - Foreign visitors at the Rizzoli Orthopaedic Institute from 1912 to 1940.

PMID- 7641536
TI  - The preliminary results of press-fit knee arthroplasty without a patellar
      component.
AB  - A total of 22 cases of Kinemax prostheses implanted consecutively from January to
      June 1990 for the treatment of primary gonarthrosis were evaluated; in these
      cases remodeling of the patella was performed, and the corresponding component of
      the prosthesis was not used. The mean age of the patients was 64 years, mean
      follow-up was obtained after 48 months. According to the HSS form results were:
      excellent: 9 (40.9%); good: 12 (54.5%); fair: 1 (4.6%). The postoperative
      femorotibial axis measured a mean of 173.8 degrees. There were no complications
      in the patella, only in 1 case did we observe mild anterior pain. Knee
      arthroplasty without substitution of the patella seems to guarantee good results
      in patients with primary gonarthrosis, as long as patellar reconstruction is
      performed and correct femoropatellar alignment is guaranteed, as well as recovery
      of the femorotibial axis with accurate positioning of the prosthetic components.

PMID- 7641537
TI  - The spacer block technique in revision of total knee arthroplasty with septic
      loosening.
AB  - Five cases of septic loosening of total knee arthroplasty were treated by two
      stage revision using a cement mixed with antibiotic. The spacer block was
      responsible for greater mechanical stability of the joint in the interval between
      the two stages of the operation, and the association of the antibiotic favored
      resolution of septic complications, allowing at the same time for systemic
      antibiotic treatment at doses lower than usual. In all of the cases treated
      reimplantation was performed in conditions of apparent sterility. The minimum
      amount of time between the first operation and reimplantation was 3 months,
      maximum was 5 months. Four to 18 months after reimplantation there was no
      recurrence of infection. Despite the short follow-up, the technique used appears
      to constitute a valid solution for septic complications in total knee
      arthroplasty.

PMID- 7641539
TI  - Intra-articular fractures of the knee: arthroscopic diagnosis and treatment.
AB  - Fifteen intra-articular fractures of the knee were treated by reduction under
      arthroscopic monitoring and osteosynthesis, and followed-up after an average of
      24 months. The authors expose the principles of surgery and discuss the
      advantages and the disadvantages as compared to traditional surgery.

PMID- 7641538
TI  - Arthrodesis of the knee after tumor resection: a comparison between autografts
      and allografts.
AB  - Cases of arthrodesis of the knee performed after bone tumor resection using
      autografts (Group I) and allografts (Group II) were compared (follow-up was
      comparable). The two groups show differences in type of pathology, treatment and
      length of resection. Nonetheless, the percentage of complications and the final
      results were similar. Despite the fact that arthrodesis of the knee is used less
      and less for reconstruction, it is our belief that the use of autografts should
      be substituted by allografts whenever possible.

PMID- 7641540
TI  - The Ilizarov method for the treatment of infected pseudarthrosis of the tibia:
      our experience in cases with severe lesion of the soft tissues.
AB  - Between 1985 and 1990 a total of 35 cases of infected pseudarthrosis of the tibia
      were treated by radical resection of the pseudarthrosis and corticotomy
      distraction-compression. In 5 patients there was severe lesion of the soft
      tissues with extensive loss of substance. It is the purpose of the present study
      to evaluate the effects of the use of this method on lesions of the soft tissues
      in these 5 patients.

PMID- 7641541
TI  - Osteointegrated porous-coated titanium implants.
AB  - The study deals with the bone-prosthesis interface using an in vivo experimental
      animal model in relation to loading and walking on the prosthetized hip, studied
      by force plate analysis. The interface is studied from a histological and
      morphometric point of view by means of a LECO 2001 system. Results show that
      titanium favors osteointegration according to the criteria of Branemark even in
      conditions of physiological loading; bone ingrowth (that cannot be considered a
      true process of osteointegration) was 27.6%; furthermore, we quantified two
      models of periprosthetic bone growth in an osteointegrative sense: total bone
      bonding (27.4%) and core bone bonding (bone that grows in direct contact with the
      prosthesis) that was 16.1%. Finally, osteointegration tends to be greater where
      contact between the bone and the prosthetic is closer, regardless of the type of
      prosthetic coating.

PMID- 7641542
TI  - Asymptomatic carotid disorder and hemodilution: a perioperative study in major
      orthopaedic surgery.
AB  - The aim of this study was to assess the pattern of adaptation to severe
      Haemodilution in pts with normal or stenotic carotid vessels. We enrolled 180
      consecutive pts undergoing total hip replacement: 138 pts had echo-Doppler
      documented normal carotid arteries, 10 pts had kinking and 32 pts had monolateral
      or bilateral stenosis of internal carotid arteries (lesions, class of stenosis 1
      49%). Haemoglobin values on the 4th day after surgery was 8.7 +/- 1.2 g/dl with
      no statistically significant differences in pts (patients) with carotid disorders
      versus normal pts. No pt showed clinical signs of cerebral ischemia or brain
      damage in the postoperative period. These results are consistent with
      experimental and clinical data showing that normovolaemic anaemia is well
      tolerated without disabling symptoms in pts with mild or moderate stenosis of
      carotid arteries.

PMID- 7641543
TI  - Proximal deep vein thrombosis: the use of the echoDoppler for diagnosis and
      therapeutic indications.
AB  - Our objective was to assess the impact of echo-Doppler technique on the diagnosis
      of Deep Vein Thrombosis (DVT) in major orthopedic surgery (80% of DVT diagnosed
      are asymptomatic). We therefore analyzed 200 consecutive pts submitted to
      elective surgery for total hip replacement. The postoperative echo-Doppler study
      indicated DVT in 13 pts: these pts underwent a postoperative lower limb
      phlebography. Echo-Doppler and phlebography had concordant results in 11 of 13
      echo assessed proximal DVT. These observations suggest that Duplex scanning is a
      good method to diagnose and to guide therapy for proximal DVT in orthopaedic
      clinic.

PMID- 7641544
TI  - Lateral retrovascular approach to the upper cervical spine.
AB  - The authors describe the surgical anatomy of lateral approach to the upper
      cervical spine. The approach is retrovascular retropharyngeal extraoral allowing
      for anterolateral exposure of the upper cervical column, and it may be enlarged
      posteriorly on the homolateral posterior hemiarch of C1 and C2, and/or inferiorly
      on the lower cervical column. Absolute indications to this approach are
      anterolateral fusion with transarticular screws C1-C2 and excision of skeletal
      neoplasms adjacent to the vertebral artery. For other indications such as the
      treatment of anterior neoplasms and spinal cord decompression it is preferable to
      use pre-vascular extraoral approach or transoral approach.

PMID- 7641546
TI  - Clinical and radiographic progression of fibrous dysplasia: cystic change or
      sarcoma? Description of a clinical case and review of the literature.
AB  - The clinical and radiographic progression of fibrous dysplasia may be due to a
      cystic-hemorrhagic change, or to a sarcomatous transformation. The distinction
      between these two possibilities, which is essential to treatment, depend on the
      biopsy. A case of fibrous dysplasia in a female aged 18 years is described in
      which, 3 years after pathologic fracture consolidated with non-surgical
      treatment, clinical and radiographic progression occurred, enough to suspect
      malignant transformation. Histological diagnosis showed fibrous dysplasia with a
      cartilaginous component and cystic-hemorrhagic changes, and curettage-bone
      allografting resulted in healing of the lesion.

PMID- 7641545
TI  - The sitting position in posterior access to the cervical spine for the treatment
      of neoplasm.
AB  - The authors evaluate the posterior approach to the cervical spine with the
      patient in a sitting position for the surgical treatment of neoplasms of the
      vertebral arch. Advantages and risks, particularly those related to anesthesia,
      are examined. Two cases in which the sitting position was advantageous are
      reported.

PMID- 7641547
TI  - Pulmonary metastasis of giant cell tumor.
AB  - The authors describe a case of pulmonary metastasis of giant cell tumor, the
      primary site of which was the radius. Treatment of the primary site and the
      metastasis is discussed.

PMID- 7641548
TI  - Congenital and acquired syphilis of bone: pathologic fracture with hyperplastic
      callus. A description of two cases and a review of the literature.
AB  - The authors describe two cases of syphilis of bone with multiple pathologic
      fractures. Healing of the fractures occurred over a normal period of time, with
      the production of hyperplastic callus. Differential diagnosis with tumorous and
      pseudotumorous lesions is possible based on clinical data and a history of the
      patient, as well as specific laboratory tests for syphilis; occasionally, biopsy
      is required.

PMID- 7641549
TI  - [Laparoscopic treatment of inguinal hernia. Evaluation of postoperative pain.
      Strait pre-peritoneal approach vs Shouldice operation (124 cases)].
AB  - In a prospective controlled trial comparing postoperative course, laparoscopic
      hernia repair totally pre-peritoneal approach appears significatively painless
      and more comfortable than Shouldice operation. Three criterions were used: pain
      questionnaire, visual scale, and antalgic use, during three days. These results
      partially explain a shorter delay to return to work (12 vs 31 days) after
      "laparoscopic treatment".

PMID- 7641550
TI  - [Successive cancers of the colon and rectum].
AB  - The incidence of successive cancers of the colon and rectum varies from 1.4% to
      5.1%. Among 350 malignant colorectal tumours operated in our unit, there were 7
      cases of successive cancers (2%). The mean interval between the discovery of the
      first and second cancer was 4.9 years with a range of 1 to 10 years, 3 cases
      before 2 years and 4 cases after 5 years. The diagnosis of the second cancer was
      made by coloscopy in 4 cases and was revealed by rectal bleeding in 4. CAE level
      was unchanged in all 7 patients and was not contributive to diagnosis. At
      diagnosis of the first cancer there were 5 intraparietal tumours including 2 with
      lymph node dissemination. At diagnosis of the second cancer, there were 5 cases
      of intraparietal tumours with 1 lymph node extension. An association with benign
      polyps was observed in 2 of the 7 cases at the first diagnosis and in 4 of the 7
      at the second. Prophylaxy requires complete work-up with total coloscopy at the
      diagnosis of the first cancer. Segmentary colectomy is sufficient in patients
      over 65, but we prefer total colectomy in patients under 65.

PMID- 7641551
TI  - [Gastric MALT lymphoma of low-grade malignancy. Apropos of 4 surgically treated
      cases].
AB  - From 1990 to 1993, programmed surgery was performed in four patients with
      histologically low grade malignant gastric lymphomas of mucosa-associated
      lymphoid tissue (MALT) (partial gastrectomy = 1, total gastrectomy = 3). These
      small cell lymphomas have the B phenotype and are uncommon. The clinical course
      is usually slow and classically limited to the stomach. As for other gastric
      lymphomas, there is still a certain amount of discussion as to the best
      therapeutic choice between surgery, chemotherapy and radiotherapy. Certain
      elements in the literature can help in managing these low grade gastric
      lymphomas. Recent publications report on a prospective study on primary lymphomas
      of the digestive tract, a clinical trial on single drug chemotherapy alone and
      the relationships between Helicobacter pylori and MALT lymphoma.

PMID- 7641552
TI  - [Laparoscopic surgery in the treatment of hiatal hernia and gastroesophageal
      reflux. Apropos of 172 cases].
AB  - Surgical cure of an anomaly of the oesocardial junction was performed 170 times
      in 172 patients (conversion rate 1.1%). Surgery was indication mainly due to
      complications of gastro-oesophageal reflux alone (32 cases) or associated with
      hiatal hernia. The Nissen Rosetti procedure was performed, usually with staple
      suture (excepting the pillars). A semi-Nissen was performed in 17 cases. There
      were two major postoperative complications (1.1%) due to necrotic perforation of
      the lower oesophagus or the greater curvature. Both cases required reoperation on
      the second and eighth day postoperatively. The postoperative period was
      uneventful in all the other cases and the mean hospital stay was 4 days. Follow
      up examinations included a gastroduodenal contrast study the day after the
      operation, a fibroscopy at discharge and clinical examination at consultation 7
      days later. Later follow-up examinations on day 30 and 90 were completed with a
      questionnaire or another consultation one year later. Radiography, fibroscopy or
      pH metry were ordered only for symptomatic patients. Poor functional outcome was
      observed in two cases with recurrent reflux and in five cases in which spiral
      procedures were used. Five second laparoscopic operations were successful. Almost
      all patients had dysphagia after the operation and in 17 cases balloon dilatation
      was required during the first month after surgery. Persistent dysphagia required
      the use of a candle twice in one patient. Dysphagia also persisted in one patient
      with impaired oesophageal motricity. Good and excellent results accounted for 84%
      of the patients at one year.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7641553
TI  - [Urethroplasty of the free colonic mucosa in rats. Preliminary study of the use
      of appendicular mucosa].
AB  - The various tissues used as free grafts in urethroplasties are associated with a
      high incidence of fistulae and strictures. The search for a new, more effective
      substitute had led the authors to study the possibility of using a new type of
      mucosa: appendicular mucosa. The size and cylindrical structure of the appendix
      and its easy resection make it an original and adapted urethral substitute. As
      most animals do not possess an appendix, an animal model of urethroplasty with
      colic mucosa has been used. A segmental distal urethrectomy has been performed on
      40 rats, 14 had a simple urethral stent without any urethroplasty (Group I), for
      7 wi performed the urethroplasty with a collagen tube (Group II) and for 19 an
      urethroplasty with free colic mucosa was performed (Group III), 3 to 6 weeks
      later, a macroscopic and microscopic study were realised. In group I and II the
      urethral duct developed a fibrosis and all rats had a severe stenosis when the
      stent went out. In those two groups, a urinary fistula has been developed in all
      rats except one. In group III, a neo-urethra was found. Under light microscopic
      examination a typical urothelium was observed in the mid and distal section and a
      keratinized squamous epithelium on the distal section. The results of the
      preliminary study let us believe that the digestive mucosa may be used for
      urethroplasty. Before we can propose the appendix mucosa in human surgery, it
      will be useful to perform sooner histological examination, then the genesis of
      the neo-urothelium should be understood.

PMID- 7641554
TI  - [Morphometric and radioautographic study of neuronal loss and gliosis in
      sclerosis of the hippocampus associated with temporal lobe epilepsy].
AB  - Hippocampal sclerosis is a complex combination of neuronal and glial changes. It
      is frequently associated with temporal lobe epilepsy. Six hippocampal specimen
      were obtained from patients operated on for intractable mesial temporal lobe
      epilepsy. Comparisons were made with six autopsy controls. The neuronal and glial
      cells populations were studied by morphometric quantitative analysis. The glial
      cell types were identified by immunohistochemistry procedures. Distribution of
      the central (neuronal location) and the peripheral (glial location)
      benzodiazepine (BZ) binding sites was studied by quantitative autoradiography
      using [3H]-flumazenil and [3H]-PK11195 as respective ligands. Neuronal death and
      glial proliferation with the usual HS pattern were confirmed in all cases.
      Microglial cells, labelled with KP1 antibody (resident component) and with HLA-DR
      alpha (reactive component) were qualitatively similar in patients and controls.
      Particular radial organization of numerous, long and thin astrocytic processes,
      as labelled with GFAP antibody, was observed in the molecular layer of the
      dentate gyrus in 5 cases. These fibrillary processes were intermingled with the
      granule cells, which were markedly dispersed in 4 of the cases. In comparison
      with control group, all the epileptic cases had significant selective decreased
      central-type and increased peripheral-type BZ receptor. These results were
      respectively correlated with neuronal loss and glial proliferation. Morphologic
      results suggest that a specific configuration of astrocytic cell processes may be
      associated with some of the neuronal changes of human HS. Such aspect has not
      been reported in the astroglial growth observed in animal models of limbic
      epilepsy. The lack of reactive microglia suggested the absence of recent cell
      death.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7641556
TI  - [Natural human anti-pig agglutinins. Role in the hyperacute rejection of
      xenogeneic graft in the pig-human donor-recipient combination].
AB  - Binding of human natural xenoantibodies to the graft endothelial cells is
      considered as one of the initial steps in the hyperacute rejection of a pig liver
      by human. In addition to binding to endothelial cells, human xenoantibodies also
      agglutinate pig red blood cells. We have therefore compared the anti-pig
      hemagglutinin titers with the cytotoxic activity to pig endothelial cells of a
      series of human sera. In order to determine the localisation of the human
      xenoantibodies fixation in the pig liver, we have studied by immunoperoxidase
      staining, deposits of IgG, IgM and IgA, using an ex vivo model of isolated pig
      liver perfused with human blood. Moreover, we have measured hemagglutinin titers
      in the perfusate along the perfusion. We have found a strong correlation between
      the anti-pig hemagglutinin titers and the anti-pig endothelial cell cytotoxic
      activity of human serum. Anti-pig hemagglutinin become undetectable in the
      perfusate within 4 minutes of perfusion of the pig liver with human blood. The
      sinusoids in the pig liver were the only structures with positive peroxidase
      staining. It is therefore suggested that human anti-pig hemagglutinins are in
      great part the same than human anti-pig endothelial cell cytotoxic antibodies.
      Pig red blood cells could be used to easily detect anti-pig xenoantibodies in
      human, and to adsorb xenoantibodies from the recipient before a xenograft.

PMID- 7641555
TI  - [Comparative vasoreactivity of the radial, internal mammary and gastroepiploic
      arteries. Implications in coronary surgery].
AB  - Recently, satisfactory results were obtained in a series of patients in whom the
      radial artery was used as a conduit for coronary artery bypass. However, spasm of
      this conduit was observed in four percent of patients. The aim of this study was
      to analyze the vasoreactive properties of the radial artery and to compare them
      to those of the internal mammary and the gastroepiploic arteries. Human radial
      (56 from n = 15 patients), internal mammary (77 from n = 20 patients) and
      gastroepiploic (41 from n = 12 patients) arteries ring segments were mounted on a
      strain gauge in oxygenated, normothermic, Krebs solution at optimal resting
      tension. With potassium chloride (100 mM) serving as the control, the dose
      response curves to norepinephrine, serotonin and thromboxane A2 mimetic were
      obtained, hence permitting to assess force of contraction and sensitivity.
      Functional endothelium was assessed by acetylcholine. Smooth muscle-dependent
      relaxation was assessed by sodium nitroprusside. The radial artery had stronger
      contractions to potassium chloride than the other vessels. The radial and the
      gastroepiploic arteries with endothelium presented a higher contraction force
      than the internal mammary artery in response to norepinephrine and serotonin. The
      gastroepiploic artery had a lower sensitivity to thromboxane A2 mimetic compared
      to the two other vessels. This increased reactivity of the radial artery explains
      its propensity to spasm and emphasizes the need for antispastic drugs and
      platelet inhibitors when the radial artery is used for coronary artery bypass.

PMID- 7641557
TI  - [Free fatty acids and acute pancreatitis. An in vivo experimental study].
AB  - Experimental in vitro studies support a theory which attributes a key role to
      pancreatic lipase in the physiopathology of acute pancreatitis. Pancreatic lipase
      would hydrolyse triglycerides either in circulation or in tissues, releasing Free
      Fatty Acids (F.F.A.). These F.F.A. would contribute to the genesis of necrotizing
      lesions by their detergent properties. This experimental work, tried to confirm
      this theory in vivo in rats, using the cerulein-induced pancreatitis model (four
      injections 20 micrograms/kg of cerulein subcutaneously). It has been demonstrated
      first that a five-times increase of circulating plasma F.F.A. (3.02 +/- 0.28
      mmol/l versus 0.75 +/- 0.05 mmol/l in control) dit not worsen cerulein-induced
      pancreatitis and were rather protective than deleterious. Furthermore, F.F.A.
      levels did not increase either in portal and aortic plasma during these
      pancreatitis, despite a major lipase release. There was also no increase of
      pancreatic content of F.F.A., measured by organic extraction performed on
      pancreatic homogenates. The role commonly attributed to F.F.A. in acute
      pancreatitis, based on in vitro experiments seems questionable in vivo.

PMID- 7641558
TI  - [Experimental model of pulmonary bipartition with bilateral lobe transplantation
      in dogs and application to clinical medicine].
AB  - The crucial need for donors of paediatric or small sized organs has been a great
      obstacle to overcome in organ transplantation in children or small adults. Some
      progress in adapting size of the donor organs has been achieved with surgical
      procedures for reducing the size of donor organs, partial transplantation (single
      lobe of the liver or the lung) and liver partition, offering a partial solution
      to the insufficient supply of paediatric organs. We propose an experimental model
      in the dog of lung partition associated with monolateral (series I) or bilateral
      (series II) lobe transplantation. The results have been encouraging both in terms
      of quality of healing and in morphological and functional adaptation of the
      transplanted lobes, allowing us to apply this technique of lung partition and
      bilateral lobe transplantation in human patients. The outcome has been excellent
      in the first case after 18 months follow-up.

PMID- 7641559
TI  - [Anesthesia for laparoscopic surgery].

PMID- 7641560
TI  - [Preoperative complementary tests].

PMID- 7641561
TI  - [Allergy to latex].
AB  - In France 18% of all preoperative allergic shock syndromes result from allergic
      reactions to latex. IgE antibodies mediate the immediate hypersensitivity
      reaction to natural latex proteins extracted for the rubber tree (Hevea
      brasiliensis). Sensibilization occurs after repeated direct contact of the skin
      or mucosa with latex products including gloves, urinary catheters or after
      chronic inhalation of airborne particles of latex in the operating theatre.
      Clinical expressions include skin rash, asthma or anaphylactic shock. During the
      preoperative period, the shock may occur late after induction of anaesthesia and
      after the operative procedure has begun or after the arm cuff has been released.
      In obstetrics oxytocin injection can precipitate the phenomenon. Subjects at risk
      have been clearly identified: subjects who wear gloves regularly, those working
      in an environment contaminated with airborne latex, children who have undergone
      multiple operations on malformations of the urinary tract or who have had
      repeated catheterisms (40% of the spina bifida patients are sensitized), atopic
      subjects, those allergic to exotic fruits (banana, avocado, kiwi). These patients
      should be identified during the preoperative work-up in order to perform allergy
      tests. The diagnosis of over-sensitivity should be confirmed by prick-tests and
      perhaps complete antilatex antibody assay and challenge. All material composed of
      natural latex should be avoided for these patients. Proposed alternatives include
      synthetic rubber. Hypoallergenic gloves add no further safety. The operative
      procedure should be conducted using standard techniques.

PMID- 7641563
TI  - [Lipo-aspiration, adjuvant therapy of esthetic surgery].

PMID- 7641562
TI  - [Liposuction. Bases, history and principles].

PMID- 7641564
TI  - [Lipo-suction. Esthetic indications].

PMID- 7641565
TI  - [Non-esthetic therapeutic indications for lipo-aspiration].

PMID- 7641566
TI  - [Lipoplasty in children. Further therapeutic indications].

PMID- 7641567
TI  - [Surgical complications of lipo-aspiration].

PMID- 7641568
TI  - Seasonal incidence and ecology of the tick Ixodes ricinus (Acari: Ixodidae) on
      grazing pastures in western France.
AB  - A longitudinal survey was carried out during a 2 year period in Western France to
      assess the infestation level of grazing pastures by Ixodes ricinus ticks. Four
      farms were visited once a month and each of the grazing pastures was sampled in
      the centre and at the border using the blanket dragging method. A total of 3562
      I. ricinus (34 adults, 900 nymphs and 2628 larvae) were collected and the
      infestation was significantly higher during the first year (p < 0.0001). The
      infestation level by I. ricinus varied between grazing pastures and farms.
      Grazing pastures in the vicinity of forest were more infested than the others,
      all through the study. The seasonal distribution of ticks showed peaks, with low
      fluctuations between farms, years and stages. Tick abundance could not be related
      to vegetation, but only to the vicinity of woods.

PMID- 7641569
TI  - Host-seeking behaviour by Australian ticks (Acari: Ixodidae) with differing host
      specificities.
AB  - Ticks generally detach from their hosts into sites where they are later exposed
      to host species which may or may not be suitable for infestation. The question of
      how four species of ixodid ticks, with differing specificities, behave towards
      such potential host species was examined. Observations of the generalists,
      Aponomma hydrosauri and Amblyomma limbatum and the specialists, Aponomma
      fimbriatum and Aponomma concolor, showed that the generalists were attracted to a
      wider range of potential host species than the specialists and that the larval
      stages of all tick species, regardless of specificity, contacted more potential
      host species than the adults. The interspecific differences may be attributed to
      reliance on different sets of host cues, while the intraspecific differences may
      reflect the developmental state of the sensory system.

PMID- 7641570
TI  - Biology of Ixodes (Pholeoixodes) hexagonus under laboratory conditions. Part II.
      Effect of mating on feeding and fecundity of females.
AB  - The effect of mating on the feeding and fecundity of Ixodes (Pholeoixodes)
      hexagonus females was studied under controlled laboratory conditions of 22-23
      degrees C and 98% relative humidity. The feeding period of mated females was 6-15
      days and 11-13 days for unmated females. The mean weight of the engorged mated
      females was 114.84 +/- 45.89 mg, whereas, that of the engorged unmated females
      was significantly lower (80.61 +/- 28.84 mg). During the initial slow feeding
      period, the weight of mated females increased 6.6 times. At the end of the blood
      feeding, they had increased their initial weight 35.5 times. Unmated females
      never entered the rapid engorgement phase and up to 12 days of feeding period
      their mean weight did not increase more than 9.2 times. The pre-oviposition
      periods of mated and unmated females were 6-15 days and 4-12 days, respectively.
      The mean of the egg production efficiency was 40.26 +/- 12.47% for mated females
      and 35.68 +/- 12.2% for unmated females. The mean of the mass conversion
      efficiency was 73.6 +/- 13.7% for mated females and 66.48 +/- 16.55% for unmated
      females. Sixty per cent of the eggs deposited by mated females hatched whereas
      only 1% of the eggs deposited by unmated females hatched. These results indicate
      that I. hexagonus females possess some predisposition for parthenogenesis and
      only fertility and not fecundity depends on mating.

PMID- 7641571
TI  - Keynote address: man, mice, microsomes, metabolites, and mathematics 40 years
      after the revolution.

PMID- 7641572
TI  - Dapsone-induced hemolytic anemia.
AB  - Dapsone, an old drug introduced and used almost exclusively for the treatment of
      leprosy, is now utilized in an increasing number of therapeutic situations.
      However, its hemotoxicity is potentially severe and is often dose limiting.
      Effective countermeasures, based on resolution of the mechanisms underlying
      dapsone-induced hemotoxicity, could significantly enhance the therapeutic value
      of the drug. In studies on rat red cells, we have established that the N-hydroxy
      metabolites of dapsone, DDS-NOH and MADDS-NOH, are direct-acting hemolytic
      agents, that they are formed in amounts sufficient to account for the
      hemotoxicity of the parent drug, and that the action of these toxic metabolites
      in the red cell induces premature sequestration by the spleen. Incubation of rat
      red cells with hemolytic concentrations of arylhydroxylamines leads to the
      generation of hydroxyl, glutathiyl, and hemoglobinthiyl radicals, and the
      formation of protein-glutathione mixed disulfides. Disulfide-linked adducts are
      also formed between membrane skeletal proteins and hemoglobin monomers, as well
      as between the monomeric hemoglobin units forming dimers, trimers, tetramers, and
      pentamers. Profound morphological changes are seen with change from normal
      discoidocity to an extreme nonspherocytic enchinocyte shape. Parallel studies
      with human red cells indicate that the response of human cells is qualitatively
      similar but that there are notable differences in regard to skeletal membrane
      effects. A working hypothesis for the mechanism underlying dapsone hemolytic
      activity is proposed.

PMID- 7641573
TI  - Quinone-thioether-mediated nephrotoxicity.
AB  - It is clear that quinone-thioethers possess a variety of biological and
      toxicological activity [5]. The ubiquitous nature of quinones and the high
      concentrations of GSH within cells virtually guarantees that humans will be
      exposed to the potential adverse effects of the resulting quinone-thioethers. The
      generation of a biologically reactive intermediate is usually the initial and
      necessary step that eventually results in cell death, tissue necrosis, and/or
      tumor formation. The various mechanisms in which reactive intermediates interact
      with cellular constituents and trigger events that lead to cell death or cell
      transformation, are only now becoming unravelled. Knowledge of the disposition of
      quinone-thioethers will therefore be an important prerequisite to understanding
      their mechanism of action. Studies on the occurrence and biological and
      toxicological activity of quinone-thioethers therefore will be an important area
      for future research.

PMID- 7641574
TI  - Mechanisms of the formation and disposition of reactive metabolites that can
      cause acute liver injury.
AB  - Acetaminophen and pulegone are just two examples for many agents that can form
      reactive metabolites that can cause acute liver injury. Two other classic organic
      compounds that have been extensively studied are carbon tetrachloride (for a
      recent review see Ref. 159, and for other discussions see Refs. 8 and 9) and
      bromobenzene (for review see Ref. 160). Different kinds of protein adducts of
      reactive metabolites of bromobenzene have been partially characterized [161], and
      specific antibodies to these adducts are now being used to isolate and identify
      the proteins that are modified (162). In contrast, carbon tetrachloride and other
      agents, such as the herbicide diquat, may form radicals that bind to and/or
      oxidize lipids and proteins in causing liver injury (163, 164). Therefore, the
      recent development [165] of antibodies to detect oxidative damage to proteins
      will be important in the identification and characterization of macromolecules
      that do not form adducts with reactive metabolites but are damaged oxidatively.
      Thus, some major challenges in the coming years are to identify hepatocellular
      macromolecules that are modified by reactive metabolites, and then approach the
      more difficult task of integrating this information into a time course and
      sequence of events leading to lethal hepatocellular injury.

PMID- 7641575
TI  - Stereoselective metabolism of halothane enantiomers to trifluoroacetylated liver
      proteins.

PMID- 7641576
TI  - In vivo characterization and modulation of the glutathione/glutathione S
      transferase system in cancer patients.

PMID- 7641577
TI  - Expression of mRNA for atrial natriuretic peptide receptor-A in human liver:
      detection using RT-PCR.
AB  - cDNA preparations obtained from human liver poly A+ RNA by reverse transcription
      were subjected to polymerase chain reaction. Primers used in the reaction were
      designed from the reported cDNA sequence for human placental atrial natriuretic
      peptide receptor-A (ANPRA). Sequence analysis of the amplified product
      (approximately 700 bp) showed 100% identity to the 2476-3189 bp region of the
      reported cDNA sequence of human placental ANPRA. Northern blot analysis of human
      liver poly A+ RNA fractions showed a hybridization signal at approximately 4.4
      kb, identical to the signal obtained from the poly A+ RNA fractions of human
      placenta. These results indicate the possible mRNA expression for atrial
      natriuretic peptide receptor-A in human liver.

PMID- 7641578
TI  - Molecular mechanisms of polymorphism in acetylating enzymes for arylamines and N
      hydroxyarylamines in hamster liver.

PMID- 7641579
TI  - Proline interaction with trichloromethyl and trichloromethyl peroxyl free
      radicals in a model system: studies about the nature of the reaction products
      formed.
AB  - Trichloromethyl and trichloromethyl peroxyl radicals are known to be produced
      during CCl4 biotransformation and are considered to be critical for deleterious
      effects of this haloalkane. In this work we describe our studies on the
      interaction of both free radicals with a lipid-soluble derivative of the amino
      acid proline in a model system. The analysis of the reaction products formed by
      gas chromatography-mass spectrometry of the sylilated derivatives revealed the
      formation of at least 11 reaction products under anaerobic conditions and 13
      under aerobic atmosphere. All of them were tentatively identified and all but 2
      were proline analogs. Only 3 incorporated in their structure CCl3 or CCl2
      portions of the CCl4 molecule and, consequently, most of the adducts formed would
      be missed during regular procedures most toxicologists use to determine CCl4.
      Results were analyzed in relation to the known role of proline in collagen
      metabolism and of this protein in liver cirrhosis.

PMID- 7641580
TI  - The role of covalent binding to microsomal proteins in the hepatotoxicity of
      acetaminophen.

PMID- 7641581
TI  - Alterations in chemically induced tissue injury related to all-trans-retinol
      pretreatment in rodents.
AB  - Retinol (vitamin A) is an essential nutrient which has many physiological effects
      throughout the body. Our studies have demonstrated that retinol modulation of
      immune response, through alteration of macrophage and neutrophil function, can
      have dramatic effects on the toxicity of some compounds. Based on these studies,
      our current hypothesis for retinol potentiation of chemical-induced liver injury
      is that retinol administered to rats prior to the hepatotoxicant (CCl4 and AA in
      rats; and AA, APAP, and GalN in mice) primes the Kupffer cells to a more active
      state. This may occur in part as a result of increases in chemical mediators such
      as TNF from these Kupffer cells. Following hepatocyte damage by a toxicant,
      Kupffer cells are activated to release reactive oxygen species, immune mediators,
      and chemotactic factors which all serve to enhance the inflammatory response.
      This increased inflammatory response then results in increased injury to the
      already toxicant-damaged hepatocytes. In addition, retinol modulation of toxicant
      activation and detoxification may also make important contributions to the
      potentiation of some toxicants such as AA. Retinol protection of CCl4
      hepatotoxicity in mice is more difficult to explain at this time but is possibly
      related to alterations in CCl4 metabolism in this species. Differences in
      response between pulmonary and liver macrophages (Kupffer cells) may explain the
      retinol protection from 1-NN pulmonary toxicity. Retinol may decrease the
      inflammatory response through downregulation of pulmonary macrophage function,
      thus resulting in decreased pulmonary injury. Finally, since retinol protection
      of cadmium toxicity in the liver and testis requires 7 days of retinol
      pretreatment, we suspect that retinol is inducing protective protein(s) in these
      organs. Aside from its normal biological role in rhe body, clinical medicine has
      found new uses for retinol in the treatment and prevention of some cancers, and
      in the treatment of certain dermatologic conditions. Since these patients are
      frequently administered or exposed to other potentially toxic compounds, it is
      obviously prudent and necessary to continue research into the effects of retinol
      on immune modulation and interaction with other compounds. More importantly,
      these studies demonstrate the modulation of immune function is one mechanism by
      which one chemical can influence the toxicity of another.

PMID- 7641582
TI  - Acinar factors in drug processing: protein binding, futile cycling, and
      cosubstrate.

PMID- 7641583
TI  - Biochemical factors important in Clara cell selective toxicity in the lung.

PMID- 7641584
TI  - Isotope effect studies on the cytochrome P450 enzymes.
AB  - Isotope effect experiments provide a powerful tool for study of the fundamental
      aspects of the enzymology of the cytochrome P450 enzymes. Competition between
      alternate pathways not only allows P450 isotope effects to be observed, but also
      provides mechanistic information on both oxygen activation and substrate
      oxidation. Indeed, the kind of knowledge that isotope effect studies can provide
      is not readily obtainable by other methodologies.

PMID- 7641585
TI  - Inhibition of P450 cytochromes by reactive intermediates.

PMID- 7641586
TI  - Mechanisms of acetaminophen toxicity: immunochemical detection of drug-protein
      adducts.

PMID- 7641587
TI  - Modulation of quinol/quinone-thioether toxicity by intramolecular detoxication.
AB  - A variety of cytotoxic, mutagenic, and carcinogenic conjugates of GSH require
      processing by enzymes of the mercapturic acid pathway to produce toxicity.
      However, metabolism of quinone-thioethers by gamma-GT can result in either
      activation or detoxication. For example, inhibition of gamma-GT completely
      protects against the nephrotoxicity caused by 2-bromo-bis-(glutathion-S
      yl)hydroquinone and 2,3,5-tris-(glutathion-S-ly)hydroquinone, whereas the same
      protocol potentiates the nephrotoxicity of 2,5-dichloro-3-(glutathion-S
      yl)hydroquinone and 2,5,6-trichloro-3-(glutathion-S-yl)hydroquinone. Which of
      these two scenarios occur as a consequence of metabolism by gamma-GT appears to
      be determined by the relative rate at which the product is transported into cells
      and/or interacts with cellular constituents, and the rate which the product
      undergoes intramolecular detoxication (cyclization) to a 1,4-benzothiazine. The
      same reaction may also explain why the mercapturic acid metabolite of menadione
      is nephrotoxic following systemic administration, whereas the GSH conjugate is
      without activity. Species differences exist in susceptibility to both 2-bromo-bis
      (glutathion-S-ly)hydroquinone and 2,3,5-tris(glutathion-S-ly)hydroquinone induced
      nephrotoxicity. In this case, however, susceptibility does not correlate with
      renal gamma-GT activity, but rather to differences in the rate at which the
      corresponding cysteine and N-acetylcysteine conjugates undergo N-acetylation/N
      deacetylation cycling. Thus the guinea pig--which is the only other rodent
      species (in addition to the rat), that is susceptible to 2-bromo-bis-(glutathion
      S-ly)hydroquinone and 2,3,5-tris-(glutathion-S-ly)hydroquinone mediated
      nephrotoxicity--expresses the lowest activity of renal gamma-GT but exhibits the
      highest N-deacetylation:N-acetylation ratio. Differences in kinetics of these two
      reactions therefore contribute to species susceptibility. The toxicity of
      quinol/quinone thioethers is dependent upon a number of physiological,
      biochemical, and electrochemical factors. The rates at which quinol-thioethers
      undergo oxidation, with the concomitant generation of reactive oxygen species
      (IV, Fig. 1), macromolecular arylation (V, Fig. 1), intramolecular cyclization
      (VI, Fig. 1), and acetylation-deacetylation cycling (III, Fig. 1) is dependent
      upon the substrate in question. All these factors will contribute to the cell,
      tissue, and species susceptibility of this interesting class of GSH conjugates.

PMID- 7641588
TI  - [Heart rate changes in a new generation of activity controlled pacemakers during
      stair climbing].
AB  - OBJECTIVE: A study was undertaken to determine whether a new generation of
      accelerometer controlled rate adaptive pacemakers has advantages over the older
      type of activity controlled pacemaker. PATIENTS AND METHODS: Pacemaker rates of
      21 patients (15 women, six men; mean age 64.1 [44-85] years) with the new
      pacemakers were compared with those of a control group of patients free of
      cardiac disease (four women, six men; mean age 50.5 [39-75] years) in whom a
      vibration controlled pacemaker system had been attached to the right pectoral
      area. Heart rate was monitored by a rate analyser, data recorder and rate watch
      throughout the period of activity. Step frequencies of 92, 108 and 120 steps/min
      were fixed by metronome. RESULTS: The new pacemaker responded with a rate
      increase at a step rate of 92/min (P < 0.001): from 106.6 +/- 7.9 beats/min on
      walking on the even, to 123 +/- 8.4 beats/min on stair climbing. There was a
      significant fall in frequency, to 105 +/- 11.7 beats/min, when descending steps.
      The conventional pacemakers responded with a decrease in frequency on stair
      climbing (97.2 +/- 8.7 beats/min compared with 112.6 +/- 7.4 when descending).
      CONCLUSIONS: The results indicate that the new system provides for a more
      physiological rate response. However, this difference between the older and the
      new generation of pacemakers is less marked on walking at higher step rates.

PMID- 7641589
TI  - [Significance of genotypes in chronic hepatitis C virus infection and hepatitis C
      virus induced liver cirrhosis in Germany].
AB  - INTRODUCTION AND OBJECTIVE: Hepatitis C virus (HCV) infection is characterized by
      a high chronicity rate. Several HCV genotypes have been described. As their
      distribution pattern in Germany had been unknown it was the aim of this study to
      determine it in a sizeable group of patients and to find out whether the
      genotypes differ in the severity of the disease caused by them. PATIENTS AND
      METHODS: 115 consecutive patients were studied prospectively, 62 (40 men, 22
      women) with chronic HCV infection (group 1) and 53 (36 men, 17 women) with liver
      cirrhosis caused by HCV (group 2). The genotypes were determined by line probe
      assay. RESULTS: The mean age of the patients in group 1 was significantly lower
      than that in group 2 (40.4 +/- 13.7 vs 57.1 +/- 12.1 years; P < 0.0001). In group
      1, genotype 1b was most frequent (53%; 1a: 21%, 3a: 21%, 2b: 3%, 2a: 2%).
      Genotype 1b also predominated in group 2 (78%; 1a: 17%, 2a: 4%, 3a: 2%). The
      differences in frequency between the two groups were significant regarding
      genotypes 1b (P = 0.01) and 3a (P = 0.005). Genotype 3a was found only in the
      younger patients. Mean age of patients with genotype 3a and chronic hepatitis C
      was significantly lower than that of the other patients in this group (34.2 +/-
      4.6 vs 42.0 +/- 14.8 years; P < 0.002). CONCLUSIONS: The results show that in
      Germany genotype 1b predominates and seems to be associated more often with the
      advanced stages of liver disease. The fact that genotype 3a occurs exclusively in
      younger patients points to a change in genotype spectrum: infection with this
      genotype may take a less aggressive course since fewer cases of liver cirrhosis
      have been observed.

PMID- 7641590
TI  - [Calciphylaxis].
AB  - HISTORY AND CLINICAL FINDINGS: Acute, zigzag-shaped livid skin markings developed
      on both thighs of a 55-year-old woman who had been on dialysis for 6 years.
      Within 7 days these areas increased in size to about 10 cm in diameter and
      contained central dry and painful necroses. On legs, lower arms and hands hard
      subcutaneous nodules were palpable with a diameter up to 3 mm. For many years the
      phosphate and parathormone levels, as well as alkaline phosphatase activity had
      been raised. The patient had often failed to follow treatment recommendations.
      TESTS: There were increased serum concentrations of calcium (2.8 mmol/l) and
      phosphate (1.78 mmol/l). The calcium phosphate ion product was 4.98 (mmol/l)2.
      Furthermore, there were raised levels of alkaline phosphatase (315 U/l) and
      parathormone (1076 ng/l, normal: 10-65). X-ray film of the hands showed soft
      tissue and arterial calcifications, while histological examination of a deep skin
      biopsy revealed calcium phosphate emboli of the main vessels. TREATMENT AND
      COURSE: Excision of the cutaneous necroses was followed by parathyroidectomy at
      which only three parathyroid glands were identified and removed. The parathormone
      level fell postoperatively, but rose again after 4 weeks. The fourth parathyroid
      gland was then found and removed, after which the parathormone level fell below
      measurable levels. The skin ulcers healed completely 4 weeks after the second
      operation.

PMID- 7641591
TI  - [Pharmacological effects on the complement system. Possibilities and limitations
      of anti-inflammatory therapy].

PMID- 7641592
TI  - [The bone and bone diseases. 3. Effects of sex hormones].

PMID- 7641594
TI  - [Preservation of patients' records after the expiration of the prescribed
      period].

PMID- 7641593
TI  - [Incidence and significance of therapy-associated late toxicity in Hodgkin's
      disease].

PMID- 7641596
TI  - [Reperfusion therapy in acute myocardial infarct].

PMID- 7641595
TI  - [2-mercaptobenzothiazole in baby pacifiers].

PMID- 7641597
TI  - [Reperfusion therapy in acute myocardial infarct].

PMID- 7641599
TI  - [Increased plasma level of lipid peroxidation products (F2-isoprostanes) in
      smokers].

PMID- 7641598
TI  - [Decline of the quality of male semen].

PMID- 7641600
TI  - Cefixime. A review of its therapeutic efficacy in lower respiratory tract
      infections.
AB  - Cefixime is an orally active third generation cephalosporin with in vitro
      antibacterial activity against most important lower respiratory pathogens. The
      drug is active against Haemophilus influenzae, Moraxella catarrhalis and
      penicillin-susceptible Streptococcus pneumoniae but not Staphylococcus aureus.
      Cefixime has a long elimination half-life (3 hours compared with 0.5 hours for
      cefaclor and 1.5 hours for cefalexin), which allows once daily administration.
      Several trials have established the clinical efficacy of the drug in patients
      with lower respiratory tract infection (LRTI). In comparative studies cefixime
      had similar efficacy to amoxicillin +/- clavulanic acid, cefaclor, cefalexin,
      cefuroxime axetil and clarithromycin. Trials evaluating the efficacy of cefixime
      as the oral component of intravenous to oral switch therapy have produced
      promising preliminary results although further carefully designed trials are
      needed in this area. As with certain other drugs of its class, gastrointestinal
      disturbances are the most frequently reported adverse events in patients taking
      cefixime and cases of pseudomembranous colitis have been reported. Thus, cefixime
      is an effective treatment for mild to moderate LRTI and may have a role as the
      oral component of intravenous to oral switch therapy although further well
      designed studies are needed to confirm initial favourable results in this
      important emerging area of antibacterial therapy.

PMID- 7641601
TI  - Therapeutic potential of antiarrhythmic peptides. Cellular coupling as a new
      antiarrhythmic target.

PMID- 7641602
TI  - Novel antithrombotic drugs in development.
AB  - Platelet activation plays a critical role in thromboembolic disorders, and
      aspirin remains a keystone in preventive strategies. This remarkable efficacy is
      rather unexpected, as aspirin selectively inhibits platelet aggregation mediated
      through activation of the arachidonic-thromboxane pathway, but not platelet
      aggregation induced by adenosine diphosphate (ADP), collagen and low levels of
      thrombin. This apparent paradox has stimulated investigations on the effect of
      aspirin on eicosanoid-independent effects of aspirin on cellular signalling. It
      has also fostered the search for antiplatelet drugs inhibiting platelet
      aggregation at other levels than the acetylation of platelet cyclo-oxygenase,
      such as thromboxane synthase inhibitors and thromboxane receptor antagonists. The
      final step of all platelet agonists is the functional expression of glycoprotein
      (GP) IIb/IIIa on the platelet surface, which ligates fibrinogen to link platelets
      together as part of the aggregation process. Agents that interact between
      GPIIb/IIIa and fibrinogen have been developed, which block GPIIb/IIIa, such as
      monoclonal antibodies to GPIIb/IIIa, and natural and synthetic peptides
      (disintegrins) containing the Arg-Gly-Asp (RGD) recognition sequence in
      fibrinogen and other adhesion macromolecules. Also, some non-peptide RGD mimetics
      have been developed which are orally active prodrugs. Stable analogues of
      prostacyclin, some of which are orally active, are also available. Thrombin has a
      pivotal role in both platelet activation and fibrin generation. In addition to
      natural and recombinant human antithrombin III, direct antithrombin III
      independent thrombin inhibitors have been developed as recombinant hirudin,
      hirulog, argatroban, boroarginine derivatives and single stranded DNA
      oligonucleotides (aptanes). Direct thrombin inhibitors do not affect thrombin
      generation and may leave some 'escaping' thrombin molecules unaffected.
      Inhibition of factor Xa can prevent thrombin generation and disrupt the thrombin
      feedback loop that amplifies thrombin production.

PMID- 7641604
TI  - Drug treatment associated with heart valve replacement.
AB  - This article reviews a number of specific pharmacological considerations for
      patients with prosthetic heart valves. All patients with mechanical heart valves
      should be anticoagulated. In the past, an International Normalised Ratio (INR) of
      2.5 to 4.5 has been recommended. Recent nonrandomised studies have suggested that
      a patient with a prosthetic valve who is at low risk for thromboembolic events
      could have an INR ranging from 1.8 to 3.5. The lower end of this range should
      only be used for patients at higher than average risk of haemorrhage, until
      randomised data show that levels below 2.5 may be applied universally. In high
      risk patients (particularly those with previous thromboembolic events) low dose
      aspirin should be added. During noncardiac surgery, a patient at low risk for
      thromboembolic events could be managed by discontinuing anticoagulation 3 days
      before the operation, with warfarin recommenced as soon as possible afterwards.
      Perioperative heparinisation would be appropriate in a higher risk patient. Women
      with prosthetic heart valves wishing to become pregnant should be converted to
      the use of twice-daily subcutaneous heparin injections. Patients with
      bioprosthetic valves can be managed without anticoagulation unless they have some
      other reason to require it. Patients at high risk should be treated with aspirin
      or warfarin. Thrombolytic therapy for acute valve thrombosis should be used for
      those who are haemodynamically compromised and therefore have a high risk of
      mortality from operative intervention. All patients with prosthetic heart valves
      undergoing invasive procedures potentially causing bacteraemia should receive
      antibiotic prophylaxis for endocarditis. The actual drugs used depend on the
      likely nature of the bacteraemia, and any possible patient hypersensitivity.

PMID- 7641603
TI  - Bronchiolitis. Origins and optimal management.
AB  - There is currently no prospect of an end to the annual epidemics of acute
      bronchiolitis, which cause considerable morbidity in previously healthy infants
      and are a major threat to the well-being of infants with underlying cardiac,
      respiratory or immunological disease. The respiratory syncytial virus remains the
      major cause of this condition, and prospects of developing a vaccine remain bleak
      while our understanding of the viral-host interaction remain incomplete.
      Treatment of patients with this condition has remained essentially unchanged for
      more than 30 years. Correction of hypoxia with oxygen, minimal handling to reduce
      the risk of exhaustion and careful noninvasive monitoring for complications such
      as apnoea and respiratory failure are the mainstays of management. Mortality in
      at-risk groups has fallen substantially during the past 10 years. This appears to
      be due to improved supportive and intensive care. The role of the antiviral agent
      ribavirin in the improved outcome, if any, is unclear. Other novel therapies have
      been tried, but none have been shown to significantly alter the natural history
      of the condition. The only effective preventive intervention currently available
      is strict adherence to measures designed to prevent nosocomial infection. This
      condition is likely to remain a continuing challenge to paediatricians for the
      foreseeable future.

PMID- 7641605
TI  - Guillain-Barre syndrome. Clinical manifestations and directions for treatment.
AB  - Guillain-Barre syndrome (GBS) is the commonest cause of acute neuromuscular
      paralysis in the developed world today. Patients present most commonly with a
      rapidly ascending paralysis together with sensory symptoms and variable autonomic
      involvement. The diagnosis is clinical, but lumbar puncture and nerve conduction
      studies are helpful in excluding other conditions. The improvement in prognosis
      in recent years is largely due to advances in respiratory intensive care
      management. Careful monitoring of cardiorespiratory function and in particular
      regular measurements of the vital capacity will help to predict which patients
      will require elective ventilation to prevent impending neuromuscular respiratory
      failure. The paralysed patient is susceptible to all the complications of
      immobility, in particular venous thromboembolism and hypostatic pneumonia, and
      good nursing care and physiotherapy are therefore mandatory. Autonomic
      involvement may predispose to cardiac arrhythmias and labile blood pressure. The
      prolonged nature of the illness predisposes to psychiatric complications,
      particularly depression, and this should be treated appropriately. Specific
      treatment is aimed at reducing the period of maximum disability. Both plasma
      exchange (PE) and intravenous immune globulin (IVIg) have been shown to be
      effective in randomised controlled trials. A multicentre trial is currently under
      way to determine whether PE or IVIg or PE followed by IVIg is the most effective
      treatment for this condition. Steroids alone have not been shown to be of value,
      although a trial is under way comparing the combination of IVIg and
      methylprednisolone with IVIg alone. The prognosis of GBS is generally good, with
      about 80% of patients making a full recovery, although about 5% die of
      complications.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7641608
TI  - Cleaning of endodontic instruments before use.
AB  - In this study, 120 new K-files and Hedstrom files from 3 different manufacturers
      were examined for surface debris with the scanning electron microscope. The
      instruments were examined immediately upon removal from their original packages.
      A second examination of the instruments was performed after they were cleansed in
      an ultrasonic bath. None of the studied instruments were free of metallic spurs
      or foreign particles as received from the manufacturers. The ultrasonic bath used
      together with a cleanser solution appeared to be an effective method to minimize
      the surface impurities from the manufacturing process prior to use in patients.

PMID- 7641609
TI  - Microbial flora of sinus tracts and root canals of non-vital teeth.
AB  - The occurrence of bacteria in 12 endodontically induced periodontal lesions
      associated with sinus tracts was examined. The microbial flora encountered in the
      sinus tract was compared with that of the root canal of the involved teeth which
      had not experienced any prior endodontic therapy. All microbiological samples
      taken from the sinus tract and from the root canal system contained bacteria.
      Seventy-one strains were detected in the extraradicular lesions. Of the anaerobic
      species, Fusobacterium nucleatum (7 strains), Prevotella intemedia (4 strains)
      and P. oralis (4 strains) were most frequently found. In the group of the
      facultative anaerobes Streptococcus spp. were predominant. Ninety-four strains
      were isolated from the root canal system of the 12 teeth. P. intermedia (6
      strains), P. buccae (5 strains), F. nucleatum (5 strains) and Lactobacillus
      plantarum (5 strains) were most common. In 9 cases, species present in the root
      canal could be revealed in the extraradicular lesions. It was concluded that a
      variety of microorganisms were capable of colonizing endodontically induced,
      extraradicular lesions clinically characterized by sinus tracts.

PMID- 7641606
TI  - Altretamine. A review of its pharmacodynamic and pharmacokinetic properties, and
      therapeutic potential in cancer chemotherapy.
AB  - Altretamine (hexamethylmelamine) is a cytotoxic antineoplastic agent which
      appears to require metabolic activation. Metabolic intermediates may act as
      alkylating agents; however, altretamine is not directly cross-resistant with
      classical alkylating agents. Objective response rates to orally administered
      altretamine as salvage therapy in patients with advanced ovarian cancer were 0 to
      33%, with disease stabilisation in a further 8 to 78% of patients. Response rates
      appear to be higher in patients who have responded to previous alkylating agent
      or cisplatin-based therapy. There is some evidence that addition of altretamine
      to platinum-based combination regimens used for induction therapy of advanced
      ovarian cancer may improve long term survival, particularly in patients with
      limited residual disease. Although altretamine displays some activity in small
      cell lung cancer, it is unlikely to have any clinical role in the management of
      non-ovarian cancer. Altretamine appears to be relatively well tolerated, with
      gastrointestinal, neurological and haematological toxicities being the main dose
      limiting adverse effects. However, assessment of accurate incidence rates for
      these effects is complicated by the use of altretamine with cisplatin. On the
      basis of the emerging body of clinical evidence, altretamine appears to have a
      limited role in the treatment of persistent or recurrent advanced ovarian cancer,
      primarily in patients who are potentially platinum sensitive yet intolerant of
      platinum analogues. Additionally, altretamine may be added to platinum-based
      regimens for induction therapy of advanced ovarian cancer. At the doses currently
      recommended, altretamine offers a reasonably well tolerated regimen that can be
      administered orally and is suitable for use on an outpatient basis.

PMID- 7641607
TI  - Fluconazole. An update of its antimicrobial activity, pharmacokinetic properties,
      and therapeutic use in vaginal candidiasis.
AB  - Fluconazole is a bis-triazole antifungal drug which has a pharmacokinetic profile
      characterised by its high water solubility, low affinity for plasma proteins, and
      metabolic stability. After a single 150 mg oral dose, therapeutic concentrations
      in vaginal secretions are rapidly achieved and are sustained for a duration
      sufficient to produce high clinical and mycological responses in
      nonimmunocompromised patients with vaginal candidiasis (candidosis). At this
      dosage, clinical and mycological responses have compared favourably with
      responses achieved after multiple dose regimens of other oral and intravaginal
      antifungal agents. Clinical efficacy rates have ranged between 92 and 99% at
      short term evaluation (5 days post-treatment). At 80 to 100 days post-treatment
      clinical efficacy rates of 91% have been reported. In addition, limited data
      indicate that fluconazole is more effective than placebo as prophylactic
      treatment of frequently recurring vaginal candidiasis. Single oral doses of
      fluconazole 150 mg are well tolerated. Most frequently observed adverse events
      are gastrointestinal symptoms, which are generally mild and transient in nature.
      Thus, fluconazole is a valuable alternative to established systemic and
      intravaginal azole antifungal drugs which are used to treat vaginal candidiasis.
      Moreover, in view of its favourable patient acceptability and compliance profile
      compared with alternative treatments, single-dose oral fluconazole should be
      considered as a first-line therapeutic choice for the treatment of women with
      vaginal candidiasis.

PMID- 7641610
TI  - Relation between incisal overjet and traumatic injury: a case control study.
AB  - Most previous studies have shown the prevalence of traumatic dental injuries in
      anterior teeth to increase with increasing overjet. This study identified 36
      Singapore schoolchildren, age 7-18 years, from a clinic population of 11,179, who
      had suffered dental trauma while playing contact or collision sports. A case
      control group of 36 children, matched for age, sex, race and sporting activities,
      but who had not suffered dental trauma, was selected from the same clinic
      population. Both groups were examined and the nature of injuries received,
      together with overjet measured to the nearest 0.5 mm were determined. The mean
      overjet for the trauma group was 3.42 +/- 1.45 mm and for the injured group 3.42
      +/- 1.33 mm. These means were not statistically different (p = 1.00), neither did
      the distribution of overjet between the groups differ. These data were not in
      accord with the majority of studies correlating incisal overjet and dental
      trauma, and they suggested that overjet was not a positive correlate with
      traumatic dental injury in Singapore schoolchildren.

PMID- 7641611
TI  - Effect of bisphosphonates and gallium on dentin resorption in vitro.
AB  - Replacement resorption may follow the replantation of an avulsed tooth. Currently
      there is no effective treatment for replacement resorption. The purpose of this
      study was to investigate the effect of bisphosphonates and gallium nitrate, which
      have been shown to reduce bone resorption, on cells which resorb dentin.
      Osteoclast-like cells were obtained by culturing cells from prenatal chick
      tibeas. These cells were seeded onto slices of human dentin which had been soaked
      in either saline (control), or solutions of 10(-5) M 1-hydroxyethylidene-1, 1
      bisphosphonic acid (EHBP), 10(-6) M dichloromethylene bisphosphonic acid
      (Cl2MBP), or 10(-6) M gallium nitrate. Resorption was measured by counting the
      number of resorptive lacunae produced by the cells. Results indicated that the
      experimental groups did not differ significantly from each other, but each
      exhibited significantly reduced resorption compared with saline controls (p <
      0.01). These results suggested that the experimental treatment reduced dentinal
      resorption by the osteoclast-like cells, and that these agents might be useful to
      prevent or at least postpone replacement resorption in avulsed teeth.

PMID- 7641612
TI  - Risk of endodontic treatment after insertion of conical crown retained dentures:
      a longitudinal study.
AB  - A longitudinal study was performed to assess the frequency of endodontic
      treatment after incorporation of conical crown retained dentures. The study
      population consisted of all patients being treated with conical crowns at the
      Academy of Advanced Dental Studies Karlsruhe during the years 1983-1989. The
      material comprised 655 patients with 1983 vital abutment teeth. The cases were
      included in a computer based documentation system for recording clinical relevant
      events. Event analysis by use of the Kaplan-Meier method revealed, that the
      probability of not being involved in endodontic treatment decreased to 0.67
      within an observation period of five years. Patients in the oldest age-group
      (above 65 years) showed a significantly higher risk of endodontic complications
      than younger patients. Molars exhibited a less pronounced risk than premolars and
      anterior teeth. The results confirmed the necessity of regular follow-up
      examinations after prosthetic procedures.

PMID- 7641613
TI  - Traumatic dental injuries at the Accident and Emergency Department of Singapore
      General Hospital.
AB  - The purpose of this retrospective study was to determine the occurrence and the
      type of after office-hours traumatic dental injuries managed by the Dental Unit
      of the Accident and Emergency Department at the Singapore General Hospital.
      During a 2-year period (from August 1990 to July 1992), 461 trauma patients (314
      males, 147 females) sustained injuries to 968 teeth. The distribution in
      different races of Chinese: Malay: Indian: others was 7.3: 1.3: 0.9: 0.5. The
      predominant age groups were 2-3 years, 3-4 years and 17-18 years; 71.3% of the
      teeth sustained luxation type injuries, the remaining 28.7% had fractures, 45.3%
      of the cohort had concomitant soft tissues injuries, while 13.7% had associated
      facial bone fractures. Teenager traumas were more common during school vacations.
      It is concluded that thorough standardized documentation is imperative to obtain
      baseline information on dental trauma. This could facilitate future preventive
      measures, education and research.

PMID- 7641614
TI  - Transient apical breakdown following subluxation injury: a case report.
AB  - Transient apical breakdown has been reported to occur in cases in which a
      periapical radiolucency develops and resolves without treatment following
      luxation injury. Diagnostic errors are inevitable if periapical breakdown is used
      as the sole criterion or as an overriding criterion in the decision to initiate
      root canal treatment. A clinical case report is presented in which transient
      apical breakdown occurred after a subluxation injury. The threshold to
      sensitivity tests increased yet sensitivity remained positive with the appearance
      of the periapical radiolucency. The decision was made not to initiate root canal
      treatment in spite of the radiographic appearance periapically. At the 10-month
      recall the tooth remained responsive to sensitivity tests and the apical
      radiolucency had disappeared.

PMID- 7641615
TI  - Treatment of large periapical lesions by inserting a drainage tube into the root
      canal.
AB  - Long-term drainage and depressurization is performed by inserting a stainless
      steel tube into the root canal of teeth with persisting periapical exudation.
      This article presents 2 cases of large periapical lesions showing a complete
      healing of bone after the drainage tube procedure. The tube allows lasting
      drainage, relieves the pressure and modifies the local apical environment so the
      host defense mechanism can exert repair process.

PMID- 7641616
TI  - Observation of bacteria and fungi in infected root canals and dentinal tubules by
      SEM.
AB  - The aim of this study was to observe the root canal flora and possible
      penetration of microorganisms into dentinal tubules in teeth with necrotic pulps.
      Ten infected maxillary and mandibular molars with periapical lesions were
      extracted and fixed in 2.5% phosphate-buffered glutaraldehyde solution for nine
      days. After separation from the crowns, longitudinal grooves were cut in the
      roots, and they were split into two halves. The specimens were prepared for SEM.
      The root canals and the dentinal tubules of the fractured dentin were scanned
      systematically from the cervical to the apical area of the root. Cocci and rods
      were seen in 6 specimens. Penetration of bacteria into the dentinal tubules
      ranged from 10 to 150 microns. In 4 specimens, the root canals were heavily
      invaded by yeasts. The antimicrobial effect of routinely used endodontic
      disinfectants also on yeasts may be considered in persistent root canal
      infections.

PMID- 7641617
TI  - Pulpal and periodontal reactions of immature permanent teeth in the dog to
      intrusive trauma.
AB  - Pulpal and periodontal tissues of immature incisors of 10 dogs were
      radiographically and histopathologically evaluated immediately, 7, 15, 30 and 60
      days after experimental intrusion induced by mechanical blows. Forty upper
      central and mesial lateral incisors showing incomplete root formation on
      radiographs were submitted to intrusive force. After the observation periods, the
      dogs were killed, two at a time. The hemi-maxilas were removed and processed for
      histopathologic examination. The traumatized teeth showed accelerated apical
      formation with reduced radicular length. Pulpal vitality was maintained and the
      subjacent tissues did not present irreversible changes. All traumatized teeth re
      erupted spontaneously.

PMID- 7641618
TI  - Developmental arrest of tooth bud after correction of mandibular fracture.
AB  - A case of multiple fractures of the mandible following a car accident in a five
      year-old patient is reported. The fracture line passed distal to the first molar
      tooth bud. The fracture was treated by wire osteosynthesis and skeletal fixation.
      During the ensuing 18 months, a gradual arrest of the development of the first
      molar tooth bud was radiologically observed. The eruption process had not been
      disturbed, and the tooth erupted at the age of 6 1/2 years. Since the distal root
      had completely failed to develop and the mesial roots showed a diminished size,
      the tooth was extracted. Histopathological examination revealed disturbed dentin
      apposition, there was almost complete obliteration of the pulp chamber by
      globular dentin, and evidence of root resorption.

PMID- 7641619
TI  - Replantation of 400 avulsed permanent incisors. 1. Diagnosis of healing
      complications.
AB  - A material of 322 patients with 400 avulsed and replanted permanent teeth were
      followed prospectively in the period from 1965 to 1988 (mean observation period =
      5.1 yrs). The age of the patients at the time of replantation ranged from 5 to 52
      yrs (mean = 13.7 yrs and median = 11.0 yrs). Standardized patient records were
      used through the entire period in order to obtain valid data concerning the
      extent of injury and treatment provided. At the follow-up period, pulpal and
      periodontal healing were monitored by clinical examination, mobility testing and
      standardized radiographic controls. Thirty-two of the replanted teeth (8%) showed
      pulpal healing. When related to teeth with incomplete root formation, where
      pulpal revascularization was anticipated (n = 94) the frequency of pulpal healing
      was 34%. Periodontal ligament healing (i.e. with no evidence of external root
      resorption) was found in 96 teeth (24%). Gingival healing was found in 371 teeth
      (93%). During the observation period, 119 teeth (30%) were extracted. Tooth loss
      was slightly more frequent in teeth with incomplete root formation at the time of
      replantation than in teeth with completed root formation.

PMID- 7641620
TI  - Replantation of 400 avulsed permanent incisors. 2. Factors related to pulpal
      healing.
AB  - Four hundred avulsed and replanted permanent teeth were examined for pulpal
      healing. In 110 teeth, the apical foramen was either open or half-open. In 16
      teeth, the pulps were extirpated prophylactically. Thus, pulpal revascularization
      was considered possible in 94 teeth. Revascularization occurred in 32 teeth
      (34%). Pulp necrosis could usually be demonstrated after 3 weeks. Positive pulpal
      sensibility and radiographis signs of pulp canal obliteration were usually
      observed after 6 months. The effect of various clinical factors was examined,
      such as sex, age, type of tooth replanted, stage of root formation, type and
      length of extra-alveolar storage, clinical contamination of the root surface,
      type of cleansing procedure of the root surface, type and length of splinting and
      the use of antibiotics. Finally, the width of the apical foramen and the length
      of the root canal were measured on radiographs taken at the time of injury. A
      multivariate statistical analysis revealed that pulpal revascularization was more
      frequent in teeth with shorter distances from the apical foramen to the pulp
      horns. Furthermore, that wet storage (saliva and/or saline) for more than 5 min
      decreased the chance of pulpal revascularization; whereas dry extraalveolar
      storage had a monotonous effect on pulpal revascularization, i.e. decreasing
      chance of revasculatization with increasing length of the extraalveolar dry
      storage. Based on these findings, immediate replantation after brief cleansing in
      either tap water or saline is recommended.

PMID- 7641621
TI  - Replantation of 400 avulsed permanent incisors. 3. Factors related to root
      growth.
AB  - Four hundred avulsed and replanted permanent incisors were examined for pulpal
      and periodontal healing. In 30 teeth, root formation was incomplete at the time
      of injury. Two teeth were excluded from the study due to nonphysiological
      extraalveolar storage (i.e. homemade saline). Of the 28 remaining replanted
      incisors, 7 showed subsequently completed root development, 8 partially completed
      root development and 13 arrested root development. Completed root development
      subsequent to replantation was found to be significantly related to pulpal
      revascularization, being rare in cases with pulp necrosis (5 of 15 teeth) and
      frequent after pulpal healing (11 of 13 teeth) (p = 0.01). Root development was
      not found to be significantly related to the extraalveolar storage period; but
      occurred slightly more frequently when the dry storage period was less than 45
      min. (p = 0.13). Ingrowth of bone and formation of an internal periodontal
      ligament (PDL) was found in 6 teeth and was related to arrested root formation in
      cases with pulpal healing. The explanatory factor for these findings appeared to
      be damage to the Hertwig's epithelial root sheath.

PMID- 7641622
TI  - Replantation of 400 avulsed permanent incisors. 4. Factors related to periodontal
      ligament healing.
AB  - 400 avulsed and replanted permanent teeth were examined for periodontal ligament
      (PDL) healing, using standardized radiographic and clinical examination
      procedures (i.e. percussion test and mobility test). The effect of various
      clinical factors was examined, such as age and sex of the patient, type of tooth
      replanted, presence of crown fracture or bone fracture, stage of root development
      (including apical diameter and length of the pulp), type and length of extra
      alveolar storage, clinical contamination of the root surface, type of root
      surface cleansing procedure, type and length of splinting period and antibiotic
      therapy. Surface resorption was generally diagnosed after 12 months; while
      inflammatory resorption and replacement resorption (ankylosis) were usually
      observed after 1 month and 1-2 months respectively. Most resorptive processes
      were diagnosed within the first 2-3 years. However, although rarely, even after 5
      and 10 years new resorptive processes could be diagnosed. A univariate
      statistical analysis of 272 teeth revealed 9 factors significantly related to PDL
      healing. A subsequent multivariate analysis revealed that the following 4 factors
      had the strongest impact upon PDL healing, in descending order of significance:
      Stage of root development; length of the dry extra-alveolar storage period;
      immediate replantation and length of the wet period (saliva or saline storage).
      Nonphysiological storage, such as homemade saline and sterilizing solutions
      (chloramine and alcohol) always led to root resorption. Storage in tap water for
      more than 20 minutes usually led to root resorption. The common denominator for
      all these factors related to PDL healing appears to be survival of the PDL cells
      along the root surface. Based on these findings, immediate replantation is
      recommended irrespective of stage of root development.

PMID- 7641623
TI  - In vitro endotoxin penetration of coronally unsealed endodontically treated
      teeth.
AB  - The purpose of the study was to evaluate the penetration of bacterial endotoxin
      (L.P.S.) through obturated root canals. Twenty-four single-rooted teeth were
      instrumented in a uniform manner. The root canals of 16 teeth were obturated with
      guttapercha and Roth's sealer and 8 teeth were similarly obturated but without
      sealer. The teeth were then divided into three groups. Group 1-Positive control
      (4 teeth). Teeth obturated without sealer were used. Sticky wax was softened in
      an open flame and painted over the external root surface except the apical 2 mm
      and coronal canal orifice which were left free of the sticky wax. Group 2
      Negative control (4 teeth). Again teeth without sealer comprised the teeth in
      this group. However, in this group the sticky wax covered the apical area of the
      root and the canal orifice coronally, in addition to the rest of the root. Group
      3-Experimental (16 teeth). The teeth obturated in conjunction with sealer were
      used. Otherwise the teeth were treated as in group 1. The coronal root half was
      then hermetically sealed from the apical root half so that LPS placed coronally
      could move only through the obturated canal space to the apical segment. One ml
      of water containing 100 micrograms/ml endotoxin was placed in the upper chambers
      and pyrogen-free water in the lower chambers. The upper and lower chambers were
      then tested for endotoxin at different time periods upto 21 days. The upper
      chambers tested positive for endotoxin at all test times for all teeth. All 4
      positive control teeth showed endotoxin in the lower chambers by 24 hrs.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7641625
TI  - Implications, prevention and management of subcutaneous emphysema during
      endodontic treatment.
AB  - Subcutaneous emphysema (SCE) is a possible complication of both nonsurgical and
      surgical endodontic treatment. A review of the literature pertinent to endodontic
      intervention and SCE is highlighted, while the causes of and recommendations for
      the prevention of SCE are provided. A review of the pathways whereby compressed
      air may travel through potential spaces in the head and neck is also illustrated
      in an attempt to identify the possibility of morbidity and even mortality should
      operator induced SCE occur in a patient.

PMID- 7641624
TI  - Immunoglobulins in periapical exudates of infected root canals: correlations with
      the clinical findings of the involved teeth.
AB  - This study quantified the concentrations of IgG and IgA in the periapical
      exudates obtained from 69 single-rooted teeth using enzyme-linked immunosorbent
      assays, and examined their correlation with clinical findings of the involved
      teeth. Changes in the levels of these immunoglobulins during root canal treatment
      were also investigated. The average levels of IgG (85.61 mg/ml) was significantly
      higher than that of IgA (0.65 mg/ml) (P < 0.001). The exudates from the canals
      with large lesions (> or = 1 cm in diameter on radiographs) showed significantly
      higher IgG and IgA levels than small lesions (< 1 cm in diameter) (P < 0.01). The
      tendency for these to be a decrease in the levels of IgG and IgA was observed
      following the root canal treatment. These observations suggest that IgG and IgA
      are involved in the immunopathogenesis of periapical lesions.

PMID- 7641626
TI  - Treatment of extraoral sinus tracts from traumatized teeth with apical
      periodontitis.
AB  - When a draining lesion is encountered on the skin of the face, an endodontic
      origin should always be considered in differential diagnosis. Non-surgical
      endodontic therapy, sometimes complimented by surgery, or extraction are the
      choices for the treatment of these cases. Three cases of extraoral sinus tract on
      the chin caused by necrotic pulp of traumatized lower anterior teeth are
      presented. A paste consisting of calcium hydroxide and barium sulfate powder
      mixed with glycerin was used. Usage of calcium hydroxide paste was advocated for
      rapid and successful treatment of extraoral lesions communicating with necrotic
      teeth.

PMID- 7641627
TI  - Effectiveness of nickel-titanium files for preparing curved root canals.
AB  - In this study, the effect of 2 different endodontic files on the final shape of
      curved root canals of extracted single rooted teeth were examined in the scanning
      electron microscope. The instruments tested were a newly designed nickel-titanium
      endodontic file and a conventional K-type file. The files were used with in and
      out linear movements with a circumferential motion starting with a size 15 file.
      Final preparation of the apical thirds of the canals was performed with a size 35
      file. Shaping effectiveness of the tested instruments was evaluated in terms of
      respect for conservation of the apical constriction and the presence or absence
      of ledging. Our observations revealed that more centered and tapered preparations
      were obtained with the use of the nickel-titanium files than with the
      conventional K-type files.

PMID- 7641628
TI  - Short vs. long-term calcium hydroxide treatment of established inflammatory root
      resorption in replanted dog teeth.
AB  - This study examined, histologically, the healing of intentionally produced
      inflammatory root resorption of replanted teeth in beagle dogs, treated with
      short- or long-term placement of calcium hydroxide. Thirty beagle dog incisors
      were randomly divided into four groups. In group 1 (negative control), uninfected
      incisors were extracted, the roots were longitudinally grooved and the teeth were
      replanted within 2 min. In group 2 the root canals were artificially infected
      followed by extraction, longitudinal grooving, and replantation as in group 1.
      Radiographs were taken biweekly and at the first signs of inflammatory root
      resorption or at 4 weeks, the root canals were fully instrumented and medicated
      with calcium hydroxide. In group 2, the root canals were permanently obturated
      with gutta-percha and sealer after 1 week of calcium hydroxide. The teeth in
      group 3 were treated as described in group 2 but after 1 wk the calcium hydroxide
      dressing was repacked for the duration of the study. In group 4 (positive
      control) the teeth were treated as described in groups 2 and 3 but no endodontic
      treatment was performed. Twelve weeks after the initiation of the endodontic
      treatment, sacrifice and histological preparation were carried out. In group 1,
      complete cemental repair was seen in all teeth. In group 2, five of ten teeth
      showed complete cemental repair whereas in group 3 complete cemental repair was
      seen in nine of ten teeth. None of the teeth in group 4 showed cemental repair.
      It was concluded that long-term may be more effective than short-term calcium
      hydroxide treatment of established inflammatory root resorption.

PMID- 7641629
TI  - An in vitro investigation into the shear bond strengths of two dentine-bonding
      agents used in the reattachment of incisal edge fragments.
AB  - This in vitro study investigated the shear bond strengths of sectioned bovine
      incisal edge fragments reattached using Gluma 2000 and Scotchbond 2. Teeth were
      sectioned 3 mm from the incisal edge using an Acutome with a 0.5 mm diamond wheel
      running at 90 degrees to the mesial or distal surface of the tooth. Twenty four
      incisal fragments were rebonded with each of the dentine bonding agents; a
      further 24 intact incisors were used as a control group. The control group
      required a mean fracture force of 940(+/- 144) N which was significantly greater
      (p < 0.01) than that required to fracture fragments rebonded using GLUMA 2000
      (609 +/- 116) N and Scotchbond 2 (393 +/- 97) N. The mean force required to
      fracture incisal fragments rebonded with GLUMA 2000 was significantly greater (p
      < 0.01) than that required to fracture incisal fragments rebonded with Scotchbond
      2.

PMID- 7641630
TI  - Morphologic criteria for root canal treatment of primary molars undergoing
      resorption.
AB  - The endodontic anatomy of primary molars is difficult to predict because of the
      balance of resorption and hard tissue deposition. In particular, the resorption
      causes perforating lacunae across the wall of the root, even at the furcation
      level, and modifies shape, dimension and position of endodontic apex. The
      phenomenon can be so deep as to compromise endodontic therapy. The first aim of
      the study was to verify if reliable criteria can be found for treatability in
      primary molars undergoing resorption, i.e. if it is possible to predict if
      perforating lacunae are present or not. The second aim of the study was to verify
      if other informations needed for endodontic treatment, as shape, dimension and
      location of the apex, and curvature of the root canal can be predicted. For the
      study, 80 extracted primary molars, 75 of which pulpally involved by caries, were
      selected. The treatability was evaluated in term of root length, root shape,
      dimension and shape of endodontic apex, age of the patient and X-ray index of
      resorption. The association between variables was performed by multiple
      correspondence analysis. The results suggested that root length was the most
      reliable criterion of the integrity of the root. The borderline of treatability
      was at the length of 4 mm. The position of endodontic apex related to anatomical
      apex, and the lingual related to the buccal root length were analyzed by linear
      regression analysis. The canal length was often similar to the root length (i.e.
      the endo and anatomical apices were very close) in lower and upper molars.
      However, in lower molars, if two or more canals were present in the same root, a
      discrepancy was observed between buccal and lingual root length. This finding was
      constant in first lower molars. In addition regression analysis provided a linear
      function between the lengths of the buccal and lingual side of the same root in
      lower molars. Its coefficient b was 0.73.

PMID- 7641631
TI  - Bacteremia in conjunction with endodontic therapy.
AB  - This study characterizes oral microorganisms believed to have spread from the
      root canal into the blood stream during and after endodontic therapy of teeth
      with Asymptomatic apical periodontitis. Microbiological samples were taken under
      aseptic conditions from the root canal of 26 single-rooted teeth in 26 patients.
      In the endodontic treatment of 13 of the patients (Group 1), the first 3 reamers,
      sizes 15, 20 and 25, were used to a level 2 mm beyond the apical foramen. In the
      other 13 patients (Group 2), the instrumentation ended inside the root canal 1 mm
      short of the apical foramen. Blood samples were taken from the patients during
      the instrumentation and 10 min after the treatment was completed. Anaerobic
      microorganisms were isolated from all root canals. In 7 patients of Group 1,
      Propionibacterium acnes, Peptostreptococcus prevotii, Fusobacterium nucleatum,
      Prevotella intermedia and Saccharomyces cerevisiae were recovered from the blood.
      In 4 patients of Group 2, P. intermedia, Actinomyces israelii, Streptococcus
      intermedius and Streptococcus sanguis were isolated from the blood. Biochemical
      tests and antibiograms revealed that the isolates from the root canal and blood
      had identical profiles within the patients, strongly suggesting that the
      microorganisms isolated from the blood had the root canal as their source.

PMID- 7641632
TI  - Maxillary permanent central incisor with abnormal crown size and dens
      invaginatus: case report.
AB  - An otherwise healthy young caucasian Australian was referred because of the
      unusual radiographic appearance of a maxillary permanent incisor. The tooth was
      found to have an enlarged crown with palatal cusp and dens invaginatus. Over five
      years' follow-up the tooth showed no signs of pulp necrosis. The major problem
      was the correction of the patient's esthetics as he approached adulthood.

PMID- 7641634
TI  - Post-anaesthetic outcome: the challenge of pain and related phenomena.

PMID- 7641633
TI  - A complex treatment of dens invaginatus.
AB  - Dens invaginatus is a developmental malformation of teeth. A case is presented of
      successful treatment of a peg lateral incisor with a severe dens invaginatus
      extending to the root apex. Both conventional endodontic therapy and periapical
      surgery were ineffective in resolving a persistent, long-standing sinus tract.
      Removal of the tooth in the present case would have created a difficult
      prosthetic problem. Intentional replantation, with improved access to the apical
      part of the canal was attempted as a last resort. A 10-month recall radiograph is
      presented showing successful healing of the periapical lesion. Pre-treatment and
      post-treatment photographs are presented to show successful esthetic treatment,
      using bonded composite resin.

PMID- 7641635
TI  - Wind-up and neuroplasticity: is there a correlation to clinical pain?
AB  - It is neurophysiologically and neurobiologically verified that the central
      nociceptive system can undergo changes and become hyperexcitable.
      Hyperexcitability involves wind-up (exaggerated responses) of dorsal horn
      neurones which in humans can be studied (temporal summation) by
      electrophysiological and psychophysical reactions to repeated nociceptive
      stimuli. Temporal summation occurs if repeated stimuli evoke increasing pain
      reactions. Human experimental models are adequate to investigate basic aspects
      and pharmacological modulation of summation and to bridge the gap between basic
      and clinical sciences facilitating the transfer of knowledge from basic science
      into the clinic. Human experimental investigations have confirmed animal studies
      that show that central summation is a potent mechanism in both normal and
      pathophysiological (hyperexcitable) conditions. Central summation should be
      considered as a target for the development of new centrally acting analgesics,
      for designing management regimens to treat intractable pain, and as a possible
      way of inhibiting surgically-induced afferent barrage from reaching brain centres
      (subconscious pain) during anaesthesia.

PMID- 7641636
TI  - Post-anaesthetic outcome: the challenge of pain and related phenomena.
      Proceedings of the 3rd International Symposium on Intravenous Anaesthesia.
      Geneva, Switzerland, 10-13 May 1995.

PMID- 7641637
TI  - The analgesic response to stress: genetic and gender considerations.
AB  - The brain contains neuronal circuits, activation of which by electrical
      stimulation or environmental stress causes analgesia. Both opioid and non-opioid
      forms of stimulus-induced analgesia exist, and are anatomically differentiated.
      Several transmitters have been postulated for non-opioid stimulus-induced
      analgesia, N-methyl-D-aspartic acid being a particularly likely candidate. In
      mice there are marked gender differences in the underlying neurochemical
      medication of stress-induced analgesia, the development of which is sensitive to
      the hormonal environment during early post-natal development and which changes
      with age in both sexes. Mice can be bred for a high or low analgesic response to
      stress and there is evidence that this is determined by a single gene. Operative
      pain, as a stressor, inhibits natural killer (NK) cell activity and influences
      the propensity to develop metastases when mice are inoculated with an
      experimental tumour after abdominal surgery. This can be influenced by peri
      operative morphine in analgesic doses.

PMID- 7641638
TI  - Post-operative nausea and vomiting: do they matter?
AB  - Post-operative nausea and vomiting (PONV) has been described as the 'big little
      problem'. With the marked improvement in anaesthetic-related mortality and life
      threatening morbidity, attention has increasingly focused on the control of post
      operative pain and emetic symptoms. While much effort has been rightly centred on
      attempts to reduce post-operative pain, not enough attention has been given to
      the management of PONV. Yet many patients consider this complication to be as
      debilitating as the pain associated with the surgical procedure. With the advent
      of newer drugs such as the anti-serotonin agents (e.g. ondansetron and
      granisetron), propofol and eltanolone, parenteral non-steroidal anti-inflammatory
      agents and rapid, shorter-acting neuromuscular blocking drugs that do not require
      routine antagonism, the incidence of emesis has been decreased. Abolition of the
      requirement that patients drink liquids prior to discharge from the ambulatory
      care centre has also helped to reduce PONV.

PMID- 7641639
TI  - Visceral nociception: consequences, modulation and the future.
AB  - It is widely appreciated that visceral pain differs significantly from pain that
      arises from cutaneous structures. Visceral pain is difficult for both the patient
      and physician to localize because it is diffuse in character and is typically
      referred to cutaneous structures. Further, there are differences between acute,
      post-operative visceral pain and the altered sensations associated with the so
      called functional bowel disorders (e.g. non-ulcer dyspepsia, non-cardiac chest
      pain and irritable bowel syndrome). A variety of considerations suggests that
      sensory inputs from the fiscera, like nociceptive inputs from the skin, can be
      sensitized. Accordingly, inputs from the viscera that are not typically perceived
      may give rise to discomfort and pain if either visceral afferent fibres are
      sensitized or central neurones undergo a change in excitability ('central
      sensitization') after persistent visceral input. The anatomy and potential
      mechanisms associated with visceral hyperalgesia will be considered as will new
      information about opioid modulation of visceral inputs to the spinal cord.

PMID- 7641640
TI  - Post-operative sleep disturbance: causes, factors and effects on outcome.
AB  - Post-operative sleep disturbance, with suppression of rapid eye movement sleep
      and slow wave sleep followed by a subsequent rebound, seems to be related to the
      magnitude of trauma and thereby to the surgical stress response. In this context,
      cortisol, autonomic stimulation, and certain cytokines may lead to abnormal
      sleep. Furthermore, the environment, pain and the administration of analgesics
      seem to be important factors in the precipitation of sleep abnormalities. Post
      operative sleep disturbance may contribute to the development of episodic
      hypoxaemia, haemodynamic instability and altered mental status, all of which have
      an influence on post-operative morbidity and mortality. Prevention or reduction
      of the post-operative sleep disturbance may be achieved by minimizing surgical
      trauma, changing the conventional nursing procedures, avoiding opioids and
      treating pain with non-opioid analgesics, although none of these methods has been
      thoroughly studied. Post-operative sleep disturbance represents an important
      research field, since it may have a significant adverse impact on post-operative
      outcome.

PMID- 7641641
TI  - Late post-operative hypoxaemia and organ dysfunction.
AB  - Constant and episodic hypoxaemia are common after major operations in the late
      post-operative period in the surgical ward. Recent studies have shown that
      hypoxaemia may be related to the development of myocardial ischaemia and cardiac
      arrhythmias. Experimental and clinical studies have demonstrated an adverse
      effect of tissue hypoxia on wound healing and on resistance to bacterial wound
      infections. Finally, mental confusion and surgical delirium may be related to
      inadequate arterial oxygenation during the late post-operative period. Late post
      operative constant and episodic hypoxaemia may therefore be important surgical
      risk factors, and further studies on the pathogenesis, prophylaxis and treatment
      are warranted.

PMID- 7641642
TI  - The gastrointestinal tract after anaesthesia.
AB  - Gastrointestinal tract motility may be reduced markedly after surgery with delay
      in gastric emptying. these alterations are induced partly by surgery, partly by
      the residual effects of anaesthetic agents, and particularly by opioids
      administered for post-operative pain relief. These changes may be antagonized to
      a certain extent by administration of prokinetic agents such as cisapride. Post
      operative ileus reduces the rate of mobilization and may also reduce or delay
      absorption of drugs administered by the gastrointestinal tract. Furthermore, post
      operative nausea and vomiting, multi-factorial in aetiology, may ensue and also
      be responsible for delayed mobilization, subjective discomfort and delay in
      administration of oral agents post-operatively. A serious problem may be leakage
      from bowel anastomoses. Although the causes are primarily surgical, an increase
      in bowel contractility may be deleterious and it has been suggested that
      neostigmine and morphine may be implicated in anastomotic dehiscence.

PMID- 7641643
TI  - Post-anaesthetic psychomotor and cognitive function.
AB  - Day surgery has a remarkable overall record of safety. To provide safe
      anaesthesia and as little post-anaesthetic psychomotor and cognitive impairment
      as possible after longer and more extensive operations performed in ambulatory
      surgical facilities, we must carefully assess home readiness and instruct
      patients in such a way that they receive and understand all relevant information.
      Policies for safe discharge from the hospital are most important for good outcome
      and have to be followed. If a patient does not have an escort home, the procedure
      should be cancelled or the patient should be admitted to the hospital.
      Recommendations not to drive after anaesthesia or sedation vary between 24 and 48
      hours, depending on the duration of anaesthesia. It is hoped that the recently
      introduced short-acting drugs will further improve outcome of day surgery by
      providing fast exit and early return to normal daily activities.

PMID- 7641644
TI  - Analgesia technique and post-operative morbidity.
AB  - Good analgesia does not normalize post-operative pulmonary function but is
      important in allowing measures such as post-operative physiotherapy to be applied
      following major abdominal or thoracic surgery. Clinical studies have generally
      failed to duplicate animal work on the effectiveness of pre-emptive analgesia
      possibly because the nociceptor stimuli persist as long as there is wound pain.
      Anaesthetic techniques which include sensory blockade are associated with a lower
      incidence of several post-operative complications and this improvement is more
      marked in high-risk patients. The contributions of spinal opioids to this is not
      known. Long-lasting analgesia can be provided via a catheter inserted in a
      relevant neurovascular compartment. There is no evidence that multimodal
      'balanced' analgesia offers any advantages in terms of improved outcome or
      reduction in adverse events. Whilst sophisticated methods for providing post
      operative pain relief, such as PCA and PCEA, are highly effective, they are
      appropriate for only a minority of surgical operations. An Acute Pain Service can
      delivery a traditional intermittent opioid regime effectively at relatively low
      cost.

PMID- 7641645
TI  - The sympathetic nervous system in pain.
AB  - Pain and similar stressful behavioural states are characterized by organized
      neural responses of the somatomotor, somatosensory (analgesia), autonomic and
      neuroendocrine systems. These defensive behaviours consist of confrontational
      defence, flight and quiescence. These integrated reactions of the sympathetic
      nervous system are well-orchestrated responses of the different sympathetic
      pathways to cardiovascular and other target organs which prepare the body to meet
      threatening challenges. The neural basis of the autonomic reactions is to be
      found in the target-organ specific organization of the sympathetic pathways in
      the periphery and neuraxis. The spinal reflex pathways are relatively specific
      for putative nociceptive responses of the sympathetic nervous systems. The
      medulla oblongata and hypothalamus contain the circuits for the specific
      homeostatic regulations in which the sympathetic nervous system is involved. The
      mesencephalon (lateral and ventrolateral periaqueductal grey) and hypothalamus
      contain the neuronal programmes for the defensive mechanisms which are switched
      on when the organism is in pain and under stress.

PMID- 7641646
TI  - Visceral pain, referred hyperalgesia and outcome: new concepts.
AB  - Visceral pain is a poorly defined, midline sensation but after minutes or hours
      becomes 'referred' to a somatic region when it becomes sharper and better
      localized. Referred pain may manifest either with or without hyperalgesia.
      Hyperalgesia is more common and can be demonstrated by changes in pain threshold.
      This referred hyperalgesia is probably sustained by central mechanisms, involving
      a spinal focus facilitating neuronal signals coming from somatic structures. Once
      established, the central changes may become independent of the peripheral input
      necessary for their initiation. With respect to post-surgical pain associated
      with operations on the viscus, the main determinant is whether or not the
      visceral pathology prior to surgery was algogenic.

PMID- 7641647
TI  - Neuroprotection: fact or fantasy?
AB  - Several strategies have been proposed for protecting the brain from ischaemic and
      hypoxic insults, based on an understanding of the pathophysiological processes
      involved. They include hypervolaemic haemodilution, anaesthesia, hypothermia,
      normoglycaemia, calcium channel blockers, adenosine modulators, NMDA- and AMPA
      receptor antagonisms and lazeroids. Some have only been shown to be effective in
      animals and some have clinical relevance. Only hypothermia is protective in a
      variety of pathological states.

PMID- 7641648
TI  - Breakthroughs in anaesthesia.

PMID- 7641649
TI  - Pharmacology of remifentanil.

PMID- 7641650
TI  - Implications of the use of remifentanil on patient outcomes.

PMID- 7641651
TI  - Remifentanil in cardiac surgery.

PMID- 7641652
TI  - Pre-emptive analgesia: evidence, current status and future directions.
AB  - Although some studies of pre-emptive analgesia have reported small reductions in
      post-operative pain or analgesic consumption in favour of pre-incisional vs. post
      incisional or post-operative treatment, most have not demonstrated any benefit at
      all. This paper reviews recent evidence supporting the effectiveness of pre
      emptive analgesia and discusses factors that may be responsible for the lack of
      consistent results. These factors include problems with the accepted definition
      of pre-emptive analgesia, the potential pre-emptive analgesic effects of other
      agents (e.g. opioids, nitrous oxide, pentobarbitone) used routinely as part of
      the general anaesthetic, the role of post-operative inflammation in initiating
      and enhancing a state of central sensitization, and the lack of a true placebo
      control condition. Given the constraints of clinical research and current
      standards of practice, it is unlikely that studies of pre-emptive analgesia using
      conventional analgesics or local anaesthetics will yield large reductions in post
      operative pain or analgesic consumption. Extending the pre-emptive treatment well
      into the post-operative period using balanced, multimodal analgesia, may prolong
      the initial advantage conferred by the pre-operative blockade and possibly
      interfere with the development of long-lasting pain.

PMID- 7641653
TI  - Anaesthesia: a perspective from the year 2005.

PMID- 7641654
TI  - Target-controlled infusions: an introductory review.

PMID- 7641655
TI  - Evaluation of the accuracy of the 'Diprifusor'.

PMID- 7641656
TI  - Effect of premedication on 'Diprifusor' TCI.

PMID- 7641657
TI  - Target-controlled infusion (TCI): a critical analysis.

PMID- 7641658
TI  - Target-controlled infusion in practice.

PMID- 7641659
TI  - Regular smokers, lifetime very light smokers, and reduced smokers: comparison of
      psychosocial and smoking characteristics in women.
AB  - This study compared stable very light smokers (VLS; less than 6 cigarettes a day)
      with regular smokers (RS; greater than 14 cigarettes a day) in a cohort of women
      followed up for 1 year. The VLS showed evidence of inhaling the cigarette smoke.
      They were not novice smokers, nor were they under particular pressure to limit
      their smoking. Among the 61 VLS, 34 had at one time smoked more than 10
      cigarettes per day. These "reduced smokers" were broadly similar to the lifetime
      VLS, who differed from RS in several important respects. In a multiple logistic
      regression, education and smoking patterns in relatives were independently
      associated with very light versus regular smoking. Familial factors and personal
      resources may protect against dependence among those who use tobacco.

PMID- 7641660
TI  - Defensive hostility: relationship to multiple markers of cardiac ischemia in
      patients with coronary disease.
AB  - Three studies assessed whether the combined traits of hostility and defensiveness
      identify a group of hostile individuals with functionally severe coronary artery
      disease (CAD). CAD patients completed the Cook-Medley Hostility Inventory (Ho)
      and the Marlowe-Crowne Social Desirability Scale (MC). Patients were classified
      into 4 groups: defensive hostile (DH: high Ho, high MC), low hostile (LH: low Ho,
      low MC), high hostile (HH: high Ho, low MC), and defensive (Def: low Ho, high
      MC). DH in comparison to HH, LH, and Def CAD patients demonstrate the greatest
      perfusion defects as measured by exercise thallium scintigraphy; DH patients
      exhibit the most frequent ischemic episodes during ambulatory
      electrocardiographic monitoring; and in a laboratory study, DH patients exhibit
      the most severe mental stress-induced ischemia assessed by echocardiography.
      Thus, the combination of high hostility and high defensiveness are associated
      with more functionally severe CAD and may predispose CAD patients to a more
      adverse prognosis.

PMID- 7641661
TI  - Cynicism, social support, and cardiovascular reactivity.
AB  - This study examined whether highly cynical individuals benefit less from social
      support during an acute stressor than individuals low in cynicism. College
      students (52 men, 52 women) performed a stressful speech task alone or in the
      presence of a supportive confederate. There was an interactive effect of social
      support and cynicism on cardiovascular reactivity: Low cynicism participants who
      received support has smaller increases in blood pressure during the speech than
      low cynicism participants without support and high cynicism participants with or
      without support. Participants' psychological stress appeared to mediate the main
      effects of support on blood pressure reactivity, but not the Support x Cynicism
      interaction. Results suggest that cynical attitudes may undermine the stress
      buffering potential of interpersonal support.

PMID- 7641662
TI  - Risk-perception: differences between adolescents and adults.
AB  - This study investigated age changes in risk perception and unrealistic optimism.
      Teenagers (n = 376) and parents (n = 160) evaluated the risk of experimental,
      occasional, and regular involvement in 14 health-related activities (e.g.,
      getting drunk). Respondents also evaluated their comparative changes of
      encountering the leading causes of morbidity and mortality. Compared with adults,
      teenagers minimized the perceived risk of experimental and occasional involvement
      in health-threatening activities. Notably, teenagers were less optimistic about
      avoiding injury and illness than were their parents, and teenagers at greatest
      risk for such misfortunes were the least optimistic about avoiding them. These
      findings do not support traditional explanations of adolescent risk taking. The
      implications of these findings for understanding and preventing health-damaging
      behavior among adolescents are discussed.

PMID- 7641663
TI  - The examination of myofascial face pain and its relationship to psychological
      distress among women.
AB  - In this study, 110 female myofascial face pain patients were assessed monthly for
      10 months on measures of pain, distress, and stressful life events. D. A. Kenny
      and A. J. Zautra's (1995) structural equation model for examining the separate
      trait, state, and error components of the variables was used to analyze the data.
      Both pain and distress had sizable trait variance, and the trait components were
      correlated. The 2 variables also showed sizable state variance, and the states of
      pain covaried with states of distress. A significant time-lagged relationship
      between the 2 variables was found: Increases in distress led to elevations in
      pain 1 month later. Stressful life events arising from major social roles were
      also associated with greater distress, but not pain. Illness events unrelated to
      the pain syndrome were associated with both pain and distress.

PMID- 7641665
TI  - Patterns of children's coping with an aversive dental treatment.
AB  - Children's disposition to monitor for threat-relevant cues predicted their coping
      strategies and levels of distress when dealing with invasive dental work. High
      monitors reported that they had engaged in greater sensory vigilance and
      avoidance strategies during treatment. Neither the tendency to monitor nor
      children's sensory vigilance was related to videotape observations of their
      attention deployment. High monitors reported increased anxiety and were rated as
      more anxious, particularly when they also engaged in high avoidance. Children's
      reports of question asking were related to videotape observations of question
      asking. In addition, children who asked more questions were rated as more anxious
      and disruptive during treatment. Individual differences in how children deal with
      a familiar--but largely uncontrollable--stressor are discussed, particularly with
      respect to the encounter phase of coping.

PMID- 7641666
TI  - Context framing to enhance HIV-antibody-testing messages targeted to African
      American women.
AB  - African American women (N = 100) recruited from an urban clinic were randomly
      assigned to view 1 of 3 experimental videotapes promoting HIV testing: (a) an
      ethnicity-matched information control videotape; (b) the same ethnicity-matched
      videotape presented by an African American woman (gender-ethnicity-matched
      control condition); or (c) an experimental videotape with a culturally relevant
      context that embedded HIV-testing information within a frame of reference
      emphasizing personal loss. Consistent with D. Kahneman and A. Tversky's (1979)
      prospect theory, women who viewed the context-framing videotape were most likely
      to have been tested during a 2-week follow-up interval. Among women who expressed
      intentions to get tested after viewing the videotapes, 63% of those in the
      message-framing condition were tested for HIV during a 2-week period compared
      with 23% in the gender-ethnicity-matched condition, and none in the ethnicity
      matched condition.

PMID- 7641664
TI  - Coping disposition, perceived risk, and psychological distress among women at
      increased risk for ovarian cancer.
AB  - The authors examined predictors of psychological distress among women who were at
      increased risk for ovarian cancer. Participants were 103 women who had at least 1
      first degree relative with ovarian cancer. Specifically, the authors tested the
      relationship between the dispositional attentional style of monitoring (the
      tendency to scan for threat-relevant information), perceptions of risk for
      ovarian cancer, intrusive thoughts regarding ovarian cancer, and psychological
      distress. Overall, this sample exhibited moderately high levels of psychological
      distress. High scores on monitoring were associated with high perceived risk for
      ovarian cancer and elevated levels of intrusive thoughts and psychological
      distress. Finally, the authors proposed and tested a path model describing the
      interrelationships between these variables. The results of this study are
      discussed in terms of their implications for treating the psychological distress
      associated with being at increased risk for ovarian cancer.

PMID- 7641667
TI  - Understanding and promoting AIDS-preventive behavior: insights from the theory of
      reasoned action.
AB  - Psychological determinants of AIDS-preventive behaviors were examined from the
      perspective of the theory of reasoned action in prospective studies of gay men,
      heterosexual university students, and heterosexual high school students. Across
      samples, preventive behaviors, and prospective intervals of 1 and 2 months'
      duration. AIDS-preventive behaviors were predicted by behavioral intentions;
      behavioral intentions were a function of attitudes and norms; and attitudes and
      norms were a function of their theorized basic underpinnings. Discussion focuses
      on the development of AIDS-prevention interventions that modify intentions,
      attitudes, and norms concerning performance of AIDS-preventive behaviors by
      targeting the empirically identified underpinnings of attitudes and norms related
      to specific preventive behaviors in specific populations of interest.

PMID- 7641668
TI  - Psychosocial predictors of AIDS risk behavior and drug use behavior in homeless
      and drug addicted women of color.
AB  - The present study examined a causal model consisting of personal and social
      resources, threat appraisal processes, coping styles, and barriers to risk
      reduction as predictors of general AIDS risk and specific drug use behaviors
      among homeless African American (N = 714) and Latina (N = 691) women. The model,
      which was based on a stress and coping framework, supported many of the
      hypothesized relationships. Active coping was associated with fewer general AIDS
      risk behaviors for both groups and less specific drug use behavior among African
      American women. Specific drug use behavior was predicted by high threat appraisal
      and avoidant coping for both groups. Ethnic differences and implications for
      intervention are discussed.

PMID- 7641669
TI  - Predictors of adoption of mammography in women under age 50.
AB  - Women in the University of North Carolina Alumni Heart Study reported their
      knowledge of and attitudes toward mammography as well as their adoption of
      mammography by 1991. Personality measured in 1988-1989 at the age of 42 was
      associated with the pattern of adoption of mammography reported 2 years later.
      Adoption of regular mammograms was predicted by conscientiousness, extraversion,
      and lower depression but not by anxiety. After adjusting for 8 traditional
      predictors of mammography shown to be significant in this population, the
      previous personality factors did not maintain their significance. When the women
      were divided into those who reported breast problems and those who did not, the
      same set of adjustment factors reduced, but did not eliminate, the association of
      conscientiousness with adoption of mammography for women without breast problems.

PMID- 7641670
TI  - The electrophysiological effects of multiple subpial transection (MST) in an
      experimental model of epilepsy induced by cortical stimulation.
AB  - Multiple subpial transection (MST) is an effective surgical therapy for patients
      with intractable seizures whose epileptogenic lesions lie in the cortex and are
      unresectable. Morrell developed this procedure and reported clinical results
      obtained using it. However, only the disappearance of epileptiform discharges
      after MST in an experimental model of epilepsy has been demonstrated. The aim of
      this study was to establish the histological changes caused by MST and evaluate
      the effects of this procedure on interneuronal discharge spread in an epilepsy
      model, i.e. acute cortical kindling in rabbits. Histologically, vertical cracks
      in the transected cortex with mild gliosis and very little tissue disruption were
      observed. Horizontal fibers across the crack had been transected, whereas
      vertical fibers and neuronal cell bodies were preserved. The stimulation-induced
      after-discharges (ADs) were analyzed: cortical hyperactivity across the
      transected zone was reduced significantly earlier than that in the control group.
      Propagation of ADs induced by the kindling effect was also inhibited. These
      results suggest that MST interrupts not only neuronal synchronization, but also
      excitatory interneuronal conduction, in this epilepsy model.

PMID- 7641671
TI  - Sustained increase of methylguanidine in rats after amygdala or hippocampal
      kindling.
AB  - Methylguanidine (MG) and guanidinoacetic acid (GAA) are known to be endogenous
      convulsants in the mammalian brain. We have reported previously that MG and GAA
      concentrations were significantly elevated bilaterally in the amygdala (AM) 7 and
      28 days after completion of AM kindling. In the present study, we investigated
      regional changes in MG and GAA in (1) AM-kindled rat brain 3 months after
      completion of kindling and (2) hippocampal (HIPP)-kindled rat brain 7 and 28 days
      after completion of kindling, using high-performance liquid chromatography. MG
      was increased significantly in the kindled AM 3 months after completion of AM
      kindling (76%, P < 0.05). Significant increases in MG levels were also found 7
      and 28 days after completion of HIPP kindling (124%, P < 0.025 and 110%, P <
      0.05, respectively) in the left AM, ipsilateral to the kindled site. GAA
      increased significantly (93%, P < 0.025) only in the left AM, ipsilateral to the
      kindled site, 7 days after completion of HIPP kindling. These results, together
      with our previous data, indicate that long-lasting increases of MG occur in the
      AM regardless of kindled foci, and may be important in producing neuronal
      hyperexcitability in kindled epileptogenesis.

PMID- 7641672
TI  - The roles of semantic networks and search efficiency in verbal fluency
      performance in intractable temporal lobe epilepsy.
AB  - Two competing hypotheses (i.e., disruption of semantic networks vs. search
      inefficiency) concerning the mechanisms underlying impaired semantic verbal
      fluency in temporal lobe epilepsy (TLE) were tested within a single paradigm.
      Reports that semantic verbal fluency is more impaired in left than right TLE
      groups were confirmed by the findings that the left TLE group produced fewer
      words on a supermarket fluency task than did the normal control (NC) group, and
      that the performance of the right TLE group was intermediate to that of the left
      TLE and NC groups. Because both TLE groups generated fewer words per category of
      supermarket items sampled, and produced a higher ratio of category labels
      relative to category exemplars than did the NC group, it can be surmised that TLE
      disrupts semantic memory networks. The findings did not support the competing
      hypothesis that reduced semantic verbal fluency in TLE is a manifestation of
      inefficient search/retrieval strategies, possibly associated with distal frontal
      lobe pathophysiology. Specifically, the TLE and NC groups did not differ
      significantly in their mean number of perseverations, intrusions, or search
      efficiency (operationalized as the ratio of the number of shifts between
      categories to the number of categories sampled).

PMID- 7641673
TI  - Familial cerebral cavernous angioma: clinical analysis of a family and phenotypic
      classification.
AB  - Only a few large families with cerebral cavernous angiomas (CCA) have been
      reported. We studied 47 members of a four-generation kindred with familial CCA.
      Thirteen members are affected; of these, eleven (85%) have epilepsy, five (38%)
      have hearing loss, three (23%) have clinically significant cerebral hemorrhages,
      one has dementia and progressive pseudobulbar palsy, one has a compressive
      myelopathy, one has asymptomatic cerebral cavernous angiomas identified by MRI,
      and another has an adrenal angioma found at autopsy. We developed a phenotypic
      classification to be used in future gene mapping studies. This classification is
      based on clinical symptoms, age at onset, concurrent diagnoses, and magnetic
      resonance imaging (MRI) findings. In the context of this family, this system
      assigns each member a probability of affectedness that can be used for linkage
      analysis. We suggest that patients with epilepsy may experience transient poor
      seizure control due to bleeding from an angioma, and drugs that may induce
      bleeding from the angiomas, such as valproic acid, should be avoided.

PMID- 7641674
TI  - Adjunctive treatment of partial seizures with tiagabine: a placebo-controlled
      trial.
AB  - Tiagabine is a new antiepileptic drug which acts by a novel mechanism, inhibiting
      the reuptake of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA)
      into neurons and glia. A double-blind, placebo-controlled, crossover trial was
      undertaken, based upon a response-dependent design. Ninety-four patients with
      complex partial seizures with or without secondary generalised tonic-clonic
      seizures were recruited into an open screening phase and tiagabine was added to
      their existing drug therapy in doses titrated to reduce seizure frequency by > or
      = 25% or to the limit of tolerance. Forty-six responders were subsequently
      randomised to a double-blind crossover trial in which tiagabine was compared with
      placebo. Forty-two patients completed the trial. A significant reduction in the
      frequency of complex partial and secondary generalised tonic clonic seizures was
      seen. Twenty-six percent had a reduction of > or = 50% in the frequency of their
      complex partial seizures, and of the 27 patients who also had secondary
      generalised tonic clonic seizures, 63% experienced a reduction of > or = 50%. No
      interactions with baseline antiepileptic drugs were detected and no serious
      adverse reactions occurred. The commonest adverse events were tiredness,
      dizziness and headache. We conclude that tiagabine has promising antiepileptic
      effects. Further trials are underway.

PMID- 7641675
TI  - The nature of epilepsy in the general population. I. Characteristics of patients
      receiving medication for epilepsy.
AB  - The study is a community-based study carried out in the UK to determine the
      characteristics of patients receiving treatment for epilepsy, with particular
      reference to the duration, nature and severity of epilepsy. 119 participating
      general practitioners distributed questionnaires to 2528 patients taking
      medication for epilepsy. Information requested included the age and sex
      distribution of the patients, seizure type, duration of epilepsy and frequency of
      seizures, employment status of the patients, and state benefits received. 1628
      patients replied. The prevalence of people receiving treatment for epilepsy was
      estimated at 4.5/1000. Fourteen per cent were under the age of 20 years and 23%
      were aged 60 or more. Seventy per cent had had epilepsy for at least 5 years,
      while 8% had been diagnosed in the previous year. Fifty-three per cent had had
      one or more seizures in the year prior to the survey, and 20% had seizures at
      least monthly on average. Most patients had seizures of partial origin. The rate
      of unemployment and receipt of social security benefits was higher than in the
      general population. The study indicates that the majority of patients receiving
      treatment for epilepsy in the community have long-standing epilepsy, often
      intractable to medical treatment, and associated with considerable social
      handicap. Health care planning should take this into account.

PMID- 7641676
TI  - The nature of epilepsy in the general population. II. Medical care.
AB  - The medical care received by an unselected population of patients with epilepsy
      identified from the lists of 119 general practitioners in the UK was evaluated
      and compared with established standards. The study was carried out by
      questionnaire distributed to the patients and their general practitioners.
      Information was collected about hospital referral patterns, the doctor
      responsible for follow-up, investigations performed, attendances at Accident and
      Emergency (A&E) departments, hospital admissions, medication, and the information
      supplied to patients. Eighty-one per cent of patients had been referred to a
      hospital outpatient clinic, and 28% were under continuing hospital follow-up.
      Only 6% had been seen in a specialist epilepsy clinic. The majority had had an
      electroencephalogram (EEG), but less than half a CT scan. Forty-three per cent
      had attended an A&E department on account of epilepsy, and 47% had required
      hospital admission. Sixty-five per cent of patients were on monotherapy, mostly
      phenytoin, carbamazepine or sodium valproate: a significant proportion also took
      phenobarbitone. Except for the issues of free prescriptions and driving, patients
      could remember being given little information about epilepsy, and this was the
      most common source of dissatisfaction. The study suggests many accepted
      recommendations about the care of people with epilepsy are not followed, with
      hospital referral patterns, a shortage of specialists epilepsy clinics, and lack
      of patient information being areas of concern.

PMID- 7641677
TI  - Fasting studies in cerebrospinal fluid and blood in children with epilepsy of
      unknown origin.
AB  - Alterations in the cerebral energy supply are likely to cause cerebral function
      disturbances. Fasting is a suitable method for studying the energy metabolism. As
      the cerebrospinal fluid (CSF) compartment reflects the brain metabolism, data in
      CSF might give information about the metabolism of fuel substrates in brain. We
      compared the biochemical data on several fuel-related components in blood and CSF
      at the end of a 40-hours fast of epileptic children with unknown origin of
      epilepsy (aged 6-15 years) with the values of a reference group of children. In
      children with primary generalized epilepsy no abnormalities were found. In
      children with complex partial epilepsy many significant abnormalities were found,
      such as low blood lactate and alanine and low CSF ketones and CSF blood ratio for
      ketones. The possible significance of the observed abnormalities are discussed.

PMID- 7641678
TI  - Metabolism of carbamazepine and co-administered anticonvulsants during pregnancy.
AB  - Urinary excretions of carbamazepine, carbamazepine-10,11-epoxide, carbamazepine
      10,11-trans-diol, 9-hydroxyacridan and 2- and 3-hydroxycarbamazepine were
      measured at various stages of pregnancy, and in the post-natal period, in ten
      epileptic women, six of whom took no other enzyme-inducing anticonvulsant and
      four of whom took such co-medication. Mean plasma carbamazepine apparent
      clearance was increased in pregnancy, but only by virtue of the increased
      clearance in the anticonvulsant co-medicated women. Alterations in the
      proportions of the carbamazepine dose cleared via the various excretion pathways
      studied were quantitatively minor, but there was evidence consistent with
      impaired conversion of carbamazepine-10,11-epoxide to carbamazepine-10,11-trans
      diol during all pregnancies studied. Clearances of carbamazepine to the various
      excretory products studied were consistent with there being (i) increased urinary
      excretion of unmetabolised drug in pregnancy, possibly related to the increased
      glomerular filtration rate, (ii) increased formation of oxidative metabolites of
      the drug, particularly in women co-medicated with enzyme-inducing
      anticonvulsants, this effect being offset, in full (in non-co-medicated women) or
      in part (in co-medicated women) by (iii) inhibition of the epoxide-diol pathway
      in pregnancy, an inhibition to which folate intake may have contributed.

PMID- 7641679
TI  - Mice deficient for the lysosomal proteinase cathepsin D exhibit progressive
      atrophy of the intestinal mucosa and profound destruction of lymphoid cells.
AB  - Mice deficient for the major lysosomal aspartic proteinase cathepsin D, generated
      by gene targeting, develop normally during the first 2 weeks, stop thriving in
      the third week and die in a state of anorexia at day 26 +/- 1. An atrophy of the
      ileal mucosa first observed in the third week progresses towards widespread
      intestinal necroses accompanied by thromboemboli. Thymus and spleen undergo
      massive destruction with fulminant loss of T and B cells. Lysosomal bulk
      proteolysis is maintained. These results suggest, that vital functions of
      cathepsin D are exerted by limited proteolysis of proteins regulating cell growth
      and/or tissue homeostasis, while its contribution to bulk proteolysis in
      lysosomes appears to be non-critical.

PMID- 7641680
TI  - Membrane insertion and assembly of ductin: a polytopic channel with dual
      orientations.
AB  - Ductin is a highly conserved and polytopic transmembrane protein which is the
      subunit c component of the vacuolar H(+)-ATPase (V-ATPase) and a component of a
      connexon channel of gap junctions. Previous studies have suggested that ductin in
      the V-ATPase has the opposite orientation of ductin in a connexon. Using an in
      vitro translation system coupled to microsomes derived from the endoplasmic
      reticulum, we show that ductin is co-translationally inserted into the membrane
      bilayer, suggesting a dependency on the signal recognition particle for
      synthesis. By attaching a C-terminal polypeptide derived from beta-lactamase and
      by using cysteine replacement coupled to chemical labelling, we show that ductin
      is inserted into the microsomal membrane in both orientations in similar
      proportions. In contrast, squid rhodopsin appears to be inserted in a single
      orientation. Changing conserved charged residues at the N-terminus of ductin does
      not affect the ratio of the two orientations. Once in the microsomal membrane,
      ductin assembles into an oligomeric complex which contains a pore accessible to a
      water-soluble probe, reminiscent of the ductin complex found in the V-ATPase and
      a connexon.

PMID- 7641681
TI  - In vivo evidence for involvement of a 58 kDa component of nuclear pore-targeting
      complex in nuclear protein import.
AB  - We recently showed that a nuclear location signal (NLS)-containing karyophile
      forms a stable complex with cytoplasmic components for nuclear pore-targeting The
      complex, termed nuclear pore-targeting complex (PTAC), contained two essential
      proteins of 54 and 90 kDa, respectively, as estimated by electrophoresis. In this
      study, we found that the 54 kDa component of PTAC is the mouse homologue of
      Xenopus importin (m-importin). Cytoplasmic injection of the antibodies raised
      against recombinant m-importin showed an inhibitory effect on nuclear import of a
      karyophile in living mammalian cells. A portion of cytoplasmically injected
      antibodies migrated rapidly into the nucleus, indicating dynamic movement of this
      protein across the nuclear envelope. Moreover, the injected antibodies co
      precipitated the karyophile, in an NLS-dependent manner, with endogenous m
      importin in the cytoplasm. These results provide in vivo evidence that m-importin
      is involved in nuclear protein import through association with a NLS in the
      cytoplasm before nuclear pore binding.

PMID- 7641682
TI  - The Pichia pastoris peroxisomal protein PAS8p is the receptor for the C-terminal
      tripeptide peroxisomal targeting signal.
AB  - The peroxisomal targeting signal 1 (PTS1), consisting of a C-terminal tripeptide
      (SKL and variants), directs polypeptides to the peroxisome matrix in
      evolutionarily diverse organisms. Previous studies in the methylotrophic yeast
      Pichia pastoris identified a 68 kDa protein, PAS8p, as a potential component of
      the PTS1 import machinery. We now report several new properties of this molecule
      which, taken together, show that it is the peroxisomal PTS1 receptor. (i) PAS8p
      is localized to and tightly associated with the cytoplasmic side of the
      peroxisomal membrane, (ii) peroxisomes of wild-type, but not of pas8 delta (null)
      mutant, P.pastoris cells bind a PTS1-containing peptide (CRYHLKPLQSKL), (iii)
      CRYHLKPLQSKL can be cross-linked to PAS8p after binding at the peroxisome
      membrane and (iv) purified PAS8p binds CRYHLKPLQSKL with high affinity (nanomolar
      dissociation constant). In addition, the tetratricopeptide repeat (TPR) domain of
      PAS8p is identified as the PTS1 binding region.

PMID- 7641683
TI  - Direct control of exocytosis by receptor-mediated activation of the
      heterotrimeric GTPases Gi and G(o) or by the expression of their active G alpha
      subunits.
AB  - The exocytotic release of potent hormones is a tightly controlled process. Its
      direct regulation without the involvement of second messengers would ensure rapid
      signal processing. In streptolysin O-permeabilized insulin-secreting cells, a
      preparation allowing dialysis of cytosolic macromolecules, activation of alpha 2
      adrenergic receptors caused pertussis toxin-sensitive inhibition of calcium
      induced exocytosis. This inhibition was mimicked very efficiently by the use of
      specific receptor-mimetic peptides, indicating the involvement of Gi and, to a
      lesser extent, of G(o). The regulation was exerted beyond the ATP-dependent step
      of exocytosis. In addition, low nanomolar amounts of pre-activated Gi/G(o)
      directly inhibited exocytosis. As transient overexpression of constitutively
      active mutants of G alpha i1, G alpha i2, G alpha i3 and G alpha o2 but not of G
      alpha o1 reproduced this regulation, the G alpha subunit alone is sufficient to
      induce inhibition. These results define exocytosis as an effector for
      heterotrimeric G-proteins and delineate the properties of the transduction
      pathway.

PMID- 7641684
TI  - Functionality and specific membrane localization of transport GTPases carrying C
      terminal membrane anchors of synaptobrevin-like proteins.
AB  - Ras-related guanine nucleotide-binding proteins of the Ypt/Rab family fulfill a
      pivotal role in vesicular protein transport both in yeast and in mammalian cells.
      Proper functioning of these proteins involves their cycling between a GTP- and a
      GDP-bound state as well as their reversible association with specific membranes.
      Here we show that the yeast Ypt1 and Sec4 proteins, essential components of the
      vesicular transport machinery, allow unimpaired vesicular transport when
      permanently fixed to membranes by membrane-spanning domains replacing their two C
      terminal cysteine residues. Membrane detachment of the GTPases therefore is not
      obligatory for transport vesicle docking to or fusion with an acceptor membrane.
      It was also found that the membrane anchors derived from different synaptobrevin
      related proteins have targeting information and direct the chimeric GTPases to
      different cellular compartments, presumably from the endoplasmic reticulum via
      the secretory pathway.

PMID- 7641685
TI  - Identification and cloning of a novel IL-15 binding protein that is structurally
      related to the alpha chain of the IL-2 receptor.
AB  - Interleukin-15 (IL-15) is a novel cytokine of the four-helix bundle family which
      shares many biological activities with IL-2, probably due to its interaction with
      the IL-2 receptor beta and gamma (IL-2R beta and gamma c) chains. We report here
      the characterization and molecular cloning of a distinct murine IL-15R alpha
      chain. IL-15R alpha alone displays an affinity of binding for IL-15 equivalent to
      that of the heterotrimeric IL-2R for IL-2. A biologically functional heteromeric
      IL-15 receptor complex capable of mediating IL-15 responses was generated through
      reconstruction experiments in a murine myeloid cell line. IL-15R alpha is
      structurally similar to IL-2R alpha; together they define a new cytokine receptor
      family. The distribution of IL-15 and IL-15R alpha mRNA suggests that IL-15 may
      have biological activities distinct from IL-2.

PMID- 7641686
TI  - Antigen-receptor induced clonal expansion and deletion of lymphocytes are
      impaired in mice lacking HS1 protein, a substrate of the antigen-receptor-coupled
      tyrosine kinases.
AB  - HS1, an intracellular protein expressed specifically in hematopoietic cells, is
      rapidly tyrosine phosphorylated after cross-linking of antigen receptors on B and
      T lymphocytes, implicating involvement of this molecule in the signal
      transduction pathways from the antigen receptors as a substrate of membrane
      associated tyrosine kinase(s). The development of lymphoid cells in HS1-deficient
      mice, generated through gene targeting, appeared normal. However, antibody
      production to T-independent antigen and proliferative responses of splenic B and
      T cells after cross-linking of the antigen receptors were impaired in these
      mutant mice. Furthermore, B cells in the peritoneal cavity of the mutant mice
      were resistant to multivalent cross-linking of the antigen receptor, which causes
      apoptosis of such cells in normal mice. Crossing the HS1-deficient mice with the
      mice harboring transgenes encoding alpha and beta chains of T-cell antigen
      receptor against a male H-Y antigen resulted in a progeny that demonstrated a
      significantly impaired ability of thymic negative selection. These results
      indicate that HS1 is a novel molecule involved in the antigen-receptor-derived
      signaling pathways and plays important roles not only in clonal expansion, but
      also in clonal deletion of B and T cells.

PMID- 7641687
TI  - Human calcium-calmodulin dependent protein kinase I: cDNA cloning, domain
      structure and activation by phosphorylation at threonine-177 by calcium
      calmodulin dependent protein kinase I kinase.
AB  - Human Ca(2+)-calmodulin (CaM) dependent protein kinase I (CaMKI) encodes a 370
      amino acid protein with a calculated M(r) of 41,337. The 1.5 kb CaMKI mRNA is
      expressed in many different human tissues and is the product of a single gene
      located on human chromosome 3. CaMKI 1-306, was unable to bind Ca(2+)-CaM and was
      completely inactive thereby defining an essential component of the CaM-binding
      domain to residues C-terminal to 306. CaMKI 1-294 did not bind CaM but was fully
      active in the absence of Ca(2+)-CaM, indicating that residues 295-306 are
      sufficient to maintain CaMKI in an auto-inhibited state. CaMKI was phosphorylated
      on Thr177 and its activity enhanced approximately 25-fold by CaMKI kinase in a
      Ca(2+)-CaM dependent manner. Replacement of Thr177 with Ala or Asp prevented both
      phosphorylation and activation by CaMKI kinase and the latter replacement also
      led to partial activation in the absence of CaMKI kinase. Whereas CaMKI 1-306 was
      unresponsive to CaMKI kinase, the 1-294 mutant was phosphorylated and activated
      by CaMKI kinase in both the presence and absence of Ca(2+)-CaM although at a
      faster rate in its presence. These results indicate that the auto-inhibitory
      domain in CaMKI gates, in a Ca(2+)-CaM dependent fashion, accessibility of both
      substrates to the substrate binding cleft and CaMKI kinase to Thr177.
      Additionally, CaMKI kinase responds directly to Ca(2+)-CaM with increased
      activity.

PMID- 7641688
TI  - A common switch in activation of the response regulators NtrC and PhoB:
      phosphorylation induces dimerization of the receiver modules.
AB  - During signal transduction, response regulators of two-component systems are
      phosphorylated in a conserved receiver module. Phosphorylation induces activation
      of the non-conserved output domain. We fused various domains of the response
      regulators NtrC, PhoB or CheB to the DNA binding domain of lambda repressor.
      Analysis of these hybrid proteins shows that the receiver modules of NtrC and
      PhoB are potential dimerization domains. In the unphosphorylated proteins, the
      ability of the receiver modules to dimerize is masked due to inhibition by their
      output domains. Inhibition can be relieved in two ways: phosphorylation of the
      receiver module or deletion of the output domain. In contrast, the receiver
      module of CheB lacks this ability for dimerization. We propose a model which
      groups response regulators into two classes. Common to both classes is the
      interaction between receiver and output domain in the unphosphorylated protein.
      In class I (e.g. NtrC and PhoB), this interaction leads to the inhibition of the
      receiver module. Phosphorylation relieves inhibition, thereby inducing activation
      via dimerization of the receiver modules. In class II (e.g. CheB), the
      interaction between receiver and output domain results in inhibition of the
      output domain. Phosphorylation relieves inhibition, thereby activating the output
      domain.

PMID- 7641689
TI  - Persistent Epstein-Barr virus infection in a human T-cell line: unique program of
      latent virus expression.
AB  - The growth transforming potential of Epstein-Barr virus (EBV) for Burkitt's
      lymphoma and nasopharyngeal carcinoma is now extended to other neoplasia, such as
      Hodgkin's disease, peripheral T-cell tumor and gastric cancer. We have generated
      an EBV recombinant with a selectable marker at the viral thymidine kinase locus.
      Recombinant EBV was successfully infected into a human T-cell line, MT-2.
      Following incubation in the selective medium, drug resistant MT-2 cell clones
      were isolated and proved to be infected with recombinant EBV. EBV-infected MT-2
      cell clones expressed EBNA 1 and LMP 1 and very little of EBNA 2, showing the
      BamHI F promoter-driven latency II form of infection, which is seen in non-B-cell
      tumors. This is the first report of in vitro generation of latency II type EBV
      infection. The present system of persistent EBV infection in T cells should be a
      good model for investigating the pathogenic role of EBV in non-B-cell tumors.

PMID- 7641690
TI  - Reduction of coproporphyrinogen oxidase level by antisense RNA synthesis leads to
      deregulated gene expression of plastid proteins and affects the oxidative defense
      system.
AB  - A full-length cDNA sequence encoding coproporphyrinogen oxidase was inserted in
      inverse orientation behind a CaMV promoter and transferred to tobacco (Nicotiana
      tabacum) by standard transformation techniques. Transformants showed reduced
      coproporphyrinogen oxidase activity and accumulation of photosensitive
      coproporphyrin(ogen), indicating antisense RNA expression. An inverse correlation
      was observed between the level of coproporphyrinogen oxidase and transformant
      phenotype. The latter is characterized by a broad range of growth retardation and
      necrosis, indicating oxidative leaf damage. Coproporphyrinogen is an apparent
      chromophore and its excitation finally leads to the production of reactive
      oxygen. Evidence is presented that indicates a direct correlation between the
      accumulation of non-metabolized coproporphyrinogen and oxidative damage to
      cellular structural components. Enzymatic and non-enzymatic antioxidants were
      investigated. Whereas superoxide dismutase activity increased in transgenic
      plants, catalase and ascorbate peroxidase activity remained constant. Tocopherol,
      rather than carotene or zeaxanthin, seemed to be involved in detoxification,
      indicating the putative localization and allocation of coproporphyrinogen.
      Expression of coproporphyrinogen oxidase antisense RNA did not significantly
      influence the level of other enzymes in the chlorophyll metabolic pathway, but
      deregulated gene expression of nuclear encoded plastid proteins. Accumulation of
      coproporphyrinogen and/or the resulting effects, such as oxidative stress,
      impairs a plastid/nuclear signal which may adapt gene expression to the plastid
      state.

PMID- 7641691
TI  - Light-responsive and transcription-enhancing elements regulate the plastid psbD
      core promoter.
AB  - The psbD operon of higher plant plastids is regulated transcriptionally through
      the activity of an upstream light-responsive promoter. To identify promoter
      elements important for the regulation, portions of the tobacco psbD 5' region
      were fused to the reporter gene, uidA, and were introduced into the tobacco
      plastid genome by targeted gene insertion. Examination of uidA mRNA accumulation
      in dark-adapted and light-treated transplastomic plants revealed that a 107 bp
      segment of psbD 5' sequence was sufficient to promote light-responsive expression
      of the reporter gene in vivo. The 107 bp promoter region contains three pairs of
      short, repeated sequences upstream of the core promoter -10/-35 elements.
      Deletion of the upstream-most A-rich sequences resulted in a 5-fold decrease in
      reporter gene mRNA accumulation, but did not affect the light response.
      Additional removal of the second and third repeated elements further reduced the
      promoter strength approximately 30-fold and almost eliminated the light-dependent
      accumulation of uidA transcripts. These data indicate that the architecture of
      chloroplast promoters is more complex than previously assumed, and may comprise
      general enhancer and regulatory elements in addition to the core promoter motifs.
      Transcriptional regulation of psbD may be mediated by the chloroplast proteins
      which were shown to interact with the repeated sequences.

PMID- 7641692
TI  - IL-2 gene expression and NF-kappa B activation through CD28 requires reactive
      oxygen production by 5-lipoxygenase.
AB  - Activation of the CD28 surface receptor provides a major costimulatory signal for
      T cell activation resulting in enhanced production of interleukin-2 (IL-2) and
      cell proliferation. In primary T lymphocytes we show that CD28 ligation leads to
      the rapid intracellular formation of reactive oxygen intermediates (ROIs) which
      are required for CD28-mediated activation of the NF-kappa B/CD28-responsive
      complex and IL-2 expression. Delineation of the CD28 signaling cascade was found
      to involve protein tyrosine kinase activity, followed by the activation of
      phospholipase A2 and 5-lipoxygenase. Our data suggest that lipoxygenase
      metabolites activate ROI formation which then induce IL-2 expression via NF-kappa
      B activation. These findings should be useful for therapeutic strategies and the
      development of immunosuppressants targeting the CD28 costimulatory pathway.

PMID- 7641693
TI  - Nuclear factor RIP140 modulates transcriptional activation by the estrogen
      receptor.
AB  - A conserved region in the hormone-dependent activation domain AF2 of nuclear
      receptors plays an important role in transcriptional activation. We have
      characterized a novel nuclear protein, RIP140, that specifically interacts in
      vitro with this domain of the estrogen receptor. This interaction was increased
      by estrogen, but not by anti-estrogens and the in vitro binding capacity of
      mutant receptors correlates with their ability to stimulate transcription. RIP140
      also interacts with estrogen receptor in intact cells and modulates its
      transcriptional activity in the presence of estrogen, but not the anti-estrogen 4
      hydroxytamoxifen. In view of its widespread expression in mammalian cells, RIP140
      may interact with other members of the superfamily of nuclear receptors and
      thereby act as a potential co-activator of hormone-regulated gene transcription.

PMID- 7641694
TI  - A positive role for nucleosome mobility in the transcriptional activity of
      chromatin templates: restriction by linker histones.
AB  - Nucleosome mobility facilitates the transcription of chromatin templates
      containing only histone octamers. Inclusion of linker histones in chromatin
      inhibits nucleosome mobility, directs nucleosome positioning and represses
      transcription. Transcriptional repression by linker histone occurs preferentially
      on templates associated with histone octamers relative to naked DNA. Mobile
      nucleosomes and the restriction of mobility by linker histones might be expected
      to exert a major influence on the accessibility of chromatin to regulatory
      molecules.

PMID- 7641695
TI  - A universally conserved region of the largest subunit participates in the active
      site of RNA polymerase III.
AB  - The largest subunits of the three eukaryotic nuclear RNA polymerase present
      extensive sequence homology with the beta' subunit of the bacterial enzymes over
      five major co-linear regions. Region d is the most highly conserved and contains
      a motif, (Y/F)NADFDGD(E/Q)M(N/A), which is invariant in all multimeric RNA
      polymerases. An extensive mutagenesis of that region in yeast RNA polymerase III
      led to a vast majority (16/22) of lethal single-site substitutions. A few
      conditional mutations were also obtained. One of them, rpc160-112, corresponds to
      a double substitution (T506I, N509Y) and has a slow growth phenotype at 25
      degrees C. RNA polymerase III from the mutant rpc160-112 was severely impaired in
      its ability to transcribe a tRNA gene in vitro. The transcription defect did not
      originate from a deficiency in transcription complex formation and RNA chain
      initiation, but was mainly due to a reduced elongation rate. Under conditions of
      substrate limitation, the mutant enzyme showed increased pausing at the intrinsic
      pause sites of the SUP4 tRNA gene and an increased rate of slippage of nascent
      RNA, as compared with the wild-type enzyme. The enzyme defect was also detectable
      with poly[d(A-T)] as template, in the presence of saturating DNA, ATP and UTP
      concentrations. The mutant enzyme behavior is best explained by a distortion of
      the active site near the growing point of the RNA product.

PMID- 7641696
TI  - Staf, a novel zinc finger protein that activates the RNA polymerase III promoter
      of the selenocysteine tRNA gene.
AB  - The selenocysteine tRNA gene (tRNA(Sec)) is atypical. Though transcribed by RNA
      polymerase III like all other tRNA genes, its basal promoter elements are
      distinct and reside essentially upstream of the coding region. In addition,
      transcription from the basal promoter is activated by a 15 bp activator element.
      In this report we describe the cloning and functional characterization of Staf
      (selenocysteine tRNA gene transcription activating factor), a novel Xenopus
      laevis transcription factor which binds to the tRNA(Sec) activator element and
      mediates its activation properties. The 600 amino acid Staf protein contains
      seven zinc fingers and a separate acidic activation domain. Seven highly
      conserved regions were detected between Staf and human ZNF76, a protein of
      unknown function, thereby aiding in predicting the locations of the functional
      domains of Staf. With the use of a novel expression assay in X.laevis oocytes we
      succeeded in demonstrating that Staf can activate the RNA polymerase III promoter
      of the tRNA(Sec) gene. This constitutes the first demonstration of the capacity
      of a cloned factor to activate RNA polymerase III transcription in vivo.

PMID- 7641697
TI  - Cdc6 is an unstable protein whose de novo synthesis in G1 is important for the
      onset of S phase and for preventing a 'reductional' anaphase in the budding yeast
      Saccharomyces cerevisiae.
AB  - S phase entry depends on cyclin-dependent kinases whose activation during late G1
      due partly to the synthesis of unstable cyclin subunits. We identify here a
      second type of unstable protein, Cdc6, whose synthesis during G1 is important for
      initiation of DNA replication. The CDC6 gene is normally transcribed at the end
      of mitosis, but in cells with a prolonged G1 phase there is a second burst of
      transcription in late G1. The former is due to Swi5, while the latter is due to
      MBF or SBF transcription factors. Small G1 cells that cannot synthesize Cdc6 in
      late G1 progress through S phase very slowly. Cells that transcribe CDC6 neither
      at the end of mitosis nor in late G1 fail to replicate DNA but, despite this,
      undergo mitosis and produce daughter cells with fractional DNA contents. This
      'reductional' anaphase occurs with almost wild-type kinetics and depends on the
      activity of G2 cyclins. Thus, cells that fail to duplicate chromosomes due to a
      cdc6 defect cannot prevent the onset of mitosis, unlike other mutants with
      replication defects. We show, by fluorescence in situ hybridization, that
      chromosomes which remain unduplicated due to a lack of Cdc6 synthesis are
      segregated intact to spindle poles during the 'reductional' anaphase.

PMID- 7641698
TI  - Autoregulation of expression of the yeast Dbp2p 'DEAD-box' protein is mediated by
      sequences in the conserved DBP2 intron.
AB  - The human p68, Saccharomyces cerevisiae DBP2 and Schizosaccharomyces pombe dbp2
      genes are closely related members of the 'DEAD-box' RNA helicase superfamily. All
      three genes contain an intron at a conserved site in RNA helicase motif V. The
      S.cerevisiae intron is unusual both for its position near the 3'-end of the open
      reading frame and for its size, 1001 nucleotides. We show here that precise
      deletion of the intron has no effect on cell viability but leads to an increase
      in Dbp2p protein expression. Inefficient splicing due to the size of the intron
      can not account for this difference because the intron is efficiently spliced in
      Dbp2p-deficient cells. Instead, there is a reciprocal relationship between the
      amount of Dbp2p in the cell and the efficiency with which DBP2 intron-containing
      genes are expressed. Inactive Dbp2p mutants are efficiently expressed from DBP2
      intron-containing plasmids, and fragments of the DBP2 intron confer Dbp2p
      responsiveness on heterologous reporter introns. This suggest that there is an
      intron-mediated negative feedback loop regulating DBP2 expression, and provides a
      possible explanation for the retention of such an unusual intron in S.cerevisiae.

PMID- 7641699
TI  - Upstream sequence elements enhance poly(A) site efficiency of the C2 complement
      gene and are phylogenetically conserved.
AB  - Poly(A) signals of mammalian pre-mRNA have been defined as an AAUAAA sequence 10
      30 nt upstream of the cleavage/poly(A) site followed by a GU/U-rich element
      immediately downstream. However, a number of viral poly(A) signals have been
      shown to possess additional signals upstream of AAUAAA that increase poly(A) site
      efficiency. We describe the first non-viral example of such an upstream sequence
      element (USE) for the poly(A) site of the human C2 complement gene. As this gene
      is very closely spaced to the related Factor B gene [the C2 poly(A) site is only
      421 bp from the transcription start site of Factor B] we have isolated this same
      intergenic sequence from four other mammals (mouse, cat, rabbit and cow). We show
      that the USE of the C2 poly(A) site is highly conserved between these five
      different mammals. Furthermore, extensive mutagenesis of the human USE indicates
      that most of the 53 nt sequence is required for full activity. The human C2
      poly(A) site does not possess any obvious downstream GU/U-rich sequences,
      although sequences immediately 3' to AAUAAA as well as 13 nt of sequence
      following the cleavage site are both required for full activity. Interestingly
      the other mammalian C2 poly(A) sites do possess significant downstream GU/U-rich
      sequences. Finally we show that all five mammalian C2 poly(A) signals are
      immediately followed by conserved signals for transcriptional termination,
      consistent with the close proximity of the downstream Factor B gene.

PMID- 7641700
TI  - Abrogation of translation initiation factor eIF-2 phosphorylation causes
      malignant transformation of NIH 3T3 cells.
AB  - The interferon induced double-stranded RNA-activated kinase, PKR, has been
      suggested to act as a tumor suppressor since expression of a dominant negative
      mutant of PKR causes malignant transformation. However, the mechanism of
      transformation has not been elucidated. PKR phosphorylates translation initiation
      factor eIF-2 alpha on Ser51, resulting in inhibition of protein synthesis and
      cell growth arrest. Consequently, it is possible that cell transformation by
      dominant negative PKR mutants is caused by inhibition of eIF-2 alpha
      phosphorylation. Here, we demonstrate that in NIH 3T3 cells transformed by the
      dominant negative PKR mutant (PKR delta 6), eIF-2 alpha phosphorylation is
      dramatically reduced. Furthermore, expression of a mutant form of eIF-2 alpha,
      which cannot be phosphorylated on Ser51 also caused malignant transformation of
      NIH 3T3 cells. These results are consistent with a critical role of
      phosphorylation of eIF-2 alpha in control of cell proliferation, and indicate
      that dominant negative PKR mutants transform cells by inhibition of eIF-2 alpha
      phosphorylation.

PMID- 7641701
TI  - A novel DNA binding and nuclease activity in domain III of Mu transposase:
      evidence for a catalytic region involved in donor cleavage.
AB  - The Mu A protein is a 75 kDa transposase organized into three structural domains.
      By severing the C-terminal region (domain III) from the remainder of the protein,
      we unmasked a novel non-specific DNA binding and nuclease activity in this
      region. Deletion analysis localized both activities to a 26 amino acid stretch
      (aa 575-600) which remarkably remained active in DNA binding and cleavage. The
      two activities were shown to be tightly linked by site-directed mutagenesis. To
      study the importance of these activities in the transposition process, an intact
      mutant transposase lacking the DNA binding and nuclease activity of domain III
      was constructed and purified. The mutant transposase was indistinguishable from
      wild-type Mu A in binding affinity for both the Mu ends and the enhancer, and in
      strand transfer activity when the cleavage step was bypassed. In contrast, the
      mutant transposase displayed defects in both synapsis and donor cleavage. Our
      results strongly suggest that the 26 amino acid region in domain III carries
      catalytic residues required for donor DNA cleavage by Mu A protein. Furthermore,
      our data suggest that an active site for donor cleavage activity in the Mu
      tetramer is assembled from domain II (metal ion binding) in one A monomer and
      domain III (DNA cleavage) in a separate A monomer. This proposal for active site
      assembly is in agreement with the recently proposed domain sharing model by Yang
      et al. (Yang, J.Y., Kim, K., Jayaram, M. and Harshey, R.M. [1995] EMBO J., 14,
      2374-2384).

PMID- 7641702
TI  - Two mutations in the HMG-box with very different structural consequences provide
      insights into the nature of binding to four-way junction DNA.
AB  - Mutation of the highly conserved tryptophan residue in the A-domain HMG-box of
      HMG1 largely, but not completely, destroys the protein tertiary structure and
      abolishes its supercoiling ability, but does not abolish structure-specific DNA
      binding to four-way junctions. Circular dichroism shows that the protein has some
      residual alpha-helix (< 10%) and does not re-fold in the presence of DNA.
      Structure-specific DNA binding might therefore be a property of some primary
      structure element, for example the N-terminal extended strand, which even in the
      unfolded protein would be held in a restricted conformation by two, largely
      trans, X-Pro peptide bonds. However, mutation of P5 or P8 of the A-domain to
      alanine does not abolish the formation of the (first) complex in a gel
      retardation assay, which probably arises from binding to the junction cross-over,
      although the P8 mutation does affect the formation of higher complexes which may
      arise from binding to the junction arms. Since mutation of P8 in the W49R mutant
      has no effect on structure-specific junction binding, we propose that some
      residual alpha-helix in the protein might be involved, implicating this element
      in the interactions of HMG-boxes generally with DNA.

PMID- 7641703
TI  - Increased frequency of mutations at A:T base pairs in the bone marrow of B6C3F1
      lacI transgenic mice exposed to 1,3-butadiene.
AB  - We have examined the spectra of mutations in a collection of 74 lacI mutants
      isolated from the bone marrow of B6C3F1 lacI transgenic mice exposed to 1,250 ppm
      1,3-butadiene (BD). Of the 49 independent mutations analyzed in the present
      study, 30 of 49 (61%) were point mutations at G:C base pairs, and 10 of 49 (20%)
      were point mutations at A:T base pairs. The remaining mutations consisted of
      small deletions and insertions and a single tandem change. An analysis of
      variance (ANOVA) on the frequency of specific mutations observed in each animal
      in this mutagenicity experiment [present study; also Sisk SC et al. (1994):
      Carcinogenesis 15:471-477] indicated that the frequency of point mutations at A:T
      base pairs is significantly greater (P < 0.05) in BD-exposed mice than in the air
      controls. In addition, there was a decrease (P < 0.05; Fisher's exact test) in
      the frequency of G:C-->A:T transitions at 5'-CpG-3' sites in BD-exposed mice
      (27%) relative to air controls (51%). These data indicate that subchronic
      exposures to BD induces an increased frequency of in vivo mutation at A:T base
      pairs in the bone marrow of B6C3F1 lacI transgenic mice.

PMID- 7641704
TI  - Effect of isopropyl-beta-D-thiogalactopyranosid induction of the lac operon on
      the specificity of spontaneous and doxorubicin-induced mutations in Escherichia
      coli.
AB  - Previous studies of doxorubicin-induced mutations employing F' lacl/lacO as an
      endogenous gene target have focused on properties of large deletions with 3'
      endpoints residing in the lacO region of the target gene. This study considers
      the influence of Lac repressor binding on the distribution of these deletions.
      Results of the DNA sequence level analysis of spontaneous and doxorubicin-induced
      i-d and lacO mutations in Escherichia coli uvrB- are reported for mutants
      isolated under conditions where Lac repression is relieved by isopropyl-beta-D
      thiogalactopyranosid (IPTG; an inducer that prevents repressor binding to lacO).
      The location of deletions isolated from doxorubicin-treated cultures in the
      presence and absence of IPTG suggests that doxorubicin preferentially focuses
      deletion endpoints adjacent to its binding sites in lacO and that the
      distribution of these deletion endpoints is not modulated by Lac repressor
      binding. In contrast, spontaneous deletion endpoints are preferentially clustered
      in the loop away from the palindromic sequences under conditions of repression.
      However, when the Lac repressor/lacO binding complex is dissociated by IPTG, the
      spontaneous 3'-deletion endpoints distribute proportionally between the putative
      stem and loop of the lacO palindrome. The single most striking effect of IPTG
      induction of the Lac operon was elimination of a "hot spot" for T:A-->C:G
      transitions at position +6 in lacO. This base substitution "hot spot," which
      accounted for 17.6% of total doxorubicin-induced mutants and 16.4% of spontaneous
      mutants in repressed bacterial cultures, accounted for approximately 1% of total
      mutations in similar experiments carried out in the presence of IPTG. A large
      number of mutations at the +6 position are induced only by doxorubicin in the
      absence of IPTG, however, suggesting that both doxorubicin-induced and
      spontaneous mutation at this transition "hot spot" are mediated by Lac repressor
      binding to lacO.

PMID- 7641705
TI  - Sources of variability in the human lymphocyte micronucleus assay: a population
      based study.
AB  - The cytokinesis block method was used to examine the intraclass correlation
      coefficient of the human lymphocyte micronucleus assay, sources of variability,
      and practical issues regarding the number of samples per subject. Twenty samples
      of 100 binucleate cells from a single phlebotomy per subject were analyzed (n =
      112), using methods to evaluate variance components. The results showed marked
      intraindividual (sampling error) variation greater than interindividual
      variation, and no between-group contribution to the total variance. The
      intraclass correlation was 41.6%, indicating that slightly greater than half of
      the total variation in micronucleus outcomes was due to error variance (i.e.,
      58.4%). After adjusting for age, the intraclass correlation coefficient decreased
      trivially from 41.6% to 39.8%. There was a strong differential gender effect,
      favoring a greater micronuclei frequency in women. In conclusion, the data
      suggest that most of the variability in our data set for the micronucleus assay
      was due to sampling error; a strong differential gender effect favoring females
      was also verified. Equally important, in terms of practical applications, our
      analysis of the appropriate number of samples per subject revealed that scoring
      greater than 1,000 cells (10 determinations per subject) yielded no substantial
      improvement in statistical sensitivity, compared to the traditional 20
      determinations. We suggest that more attention should be directed toward
      improving the assay's utility, while reducing sampling error.

PMID- 7641706
TI  - Micronuclei in mice treated with monocrotaline with and without phenobarbital
      pretreatment.
AB  - Monocrotaline is a very potent toxin, producing significant effects of
      pneumotoxicity, hepatotoxicity, and teratogenicity, as well as carcinogenicity.
      In addition, the compound has been clearly shown to be mutagenic after metabolic
      activation. The goal of the experiments reported here was to confirm the reported
      clastogenesis induced by this agent in vivo and to evaluate the impact of
      modulation of metabolic activity by phenobarbital, a potent P-450 inducer (both
      Phase I and Phase II enzymes). The method used in addressing this problem relied
      on a new technique for monitoring clastogenesis in vivo, i.e., the acridine
      orange micronucleus assay method originally exploited by Hayashi et al. [1990].
      The result of our experiments confirmed monocrotaline to be an effective
      clastogen in vivo, using the acridine orange method of assessment. The peak in
      induction of micronuclei occurred on the second day following intraperitoneal
      administration of the drug. Administration of phenobarbital prior to
      monocrotaline did appear to modulate the micronucleus induction. At 30 mg/kg bw
      monocrotaline, the pretreatment with phenobarbital appears to increase the
      intensity of monocrotaline clastogenesis, while the effect at higher doses (60
      and 125 mg/kg bw) is a reduction in potency, presumably reflecting increased
      importance of Phase II metabolism for monocrotaline at these doses. Thus the
      study reported here confirms the potent in vivo clastogenesis of monocrotaline,
      and provides evidence for a dose-related shift in mechanism for the phenomenon.

PMID- 7641707
TI  - Micronucleus frequency in spleen lymphocytes from severely malnourished rats
      during lactation.
AB  - The purpose of this ex vivo study was to determine if severe malnutrition
      increases the frequency of micronuclei in spleen lymphocytes of experimentally
      malnourished rats during lactation. Micronucleus frequencies were analyzed in
      binucleate cells produced by the cytokinesis block method. The overall
      micronucleus frequency was significantly higher in binucleate cells from
      malnourished rats (21.30/1000) as compared to that observed in control rats
      (11.50/1000). The number of binucleate cells with more than one micronucleus was
      also higher in malnourished rats than in controls (3.10/1000 vs. 1.20/1000).
      These results indicate that severe malnutrition produces cellular damage in vivo,
      as was evidenced by the increased micronucleus frequency in rat spleen
      lymphocytes in vitro. This damage may produce negative effects for the further
      development of the organism, since the spleen is an important lymphopoietic organ
      in rodents.

PMID- 7641708
TI  - In vivo DNA adduct formation by bisphenol A.
AB  - We have previously shown that bisphenol A (BPA) is oxidized to bisphenol-o
      quinone in the presence of activation system and that the chemical reaction of
      DNA or deoxyguanosine 3'-monophosphate (dGMP) with bisphenol-o-quinone produces
      adducts. In the present study, using the 32P-postlabeling technique, we have
      investigated the in vivo DNA adduct formation by BPA by examining covalent
      modification in DNA. Administration of a single or multiple dose of 200 mg/kg of
      BPA to CD1 male rats produced two major and several minor adducts in liver DNA.
      The two major in vivo adducts matched the adduct profile of DNA or dGMP-bisphenol
      o-quinone. To determine how BPA may be converted to DNA-binding metabolites,
      adducts were examined after incubation of DNA with BPA in the presence of a
      microsomal activation system. The in vitro incubation of BPA with DNA in the
      presence of a microsomal activation system revealed one major adduct and several
      minor adducts. The formation of adducts in DNA by BPA in the presence of a
      microsomal activation system was drastically decreased by known inhibitors of
      cytochrome P450. Adduct formation in DNA when cumene hydroperoxide or NADPH was
      used as a cofactor showed adducts with similar chromatographic mobilities as
      those from the reaction of dGMP-bisphenol-o-quinone. These data demonstrate that
      BPA is capable of binding covalently to DNA. DNA binding can be inhibited by the
      inhibitors of cytochrome P450. One of the DNA-binding metabolite(s) both in vitro
      and in vivo may be bisphenol-o-quinone. Covalent modifications in DNA by in vivo
      exposure of BPA may be a factor in the induction of hepatotoxicity.

PMID- 7641709
TI  - Loss of heterozygosity in asbestos-induced mutations in a human mesothelioma cell
      line.
AB  - The relationship between occupational or environmental exposure to asbestos and
      the development of mesothelioma, typically after prolonged latency, has been
      accepted as one of cause and effect. Most studies have concluded that asbestos is
      not mutagenic to mammalian cells in vitro. We have studied the potential of
      crocidolite asbestos to induce mutations in a stable mesothelioma cell line,
      using a mutation assay that measures mutation at the autosomal HLA-A locus and
      permits clonal growth of mutant cells. The mesothelioma cell line chosen is more
      akin to the in vivo target cells of asbestos than human peripheral blood
      lymphocytes used in previous studies. Exposure of mesothelioma cells in culture
      to both 200 micrograms/ml and 50 micrograms/ml crocidolite for 72 hr did not
      result in a statistically significant difference in the mutation frequency (MF)
      in the HLA-A assay when compared to the spontaneous MF in these cells. Mutations
      in the mesothelioma cells were classified according to their molecular basis.
      Notwithstanding the lack of statistically significant change in overall MF,
      molecular analysis of mutants obtained following exposure of mesothelioma cells
      to crocidolite demonstrated a statistically significant increase in the class of
      mutations arising from loss of heterozygosity (LOH) events involving the
      selection locus (HLA-A) and more distal loci. Mutations following exposure to 200
      micrograms/ml and 50 micrograms/ml crocidolite showed a greater frequency of LOH
      than did spontaneous mutants (P < 0.01 and P < 0.001, respectively). These
      results correlate with those obtained in an earlier study using lymphocytes. The
      mesothelioma cell-based assay may be useful in detecting the mutagenicity of
      other asbestiform fibers and man-made fibers.

PMID- 7641710
TI  - Streptozotocin-induced toxicity in CHO-9 and V79 cells.
AB  - The cytotoxicity of streptozotocin (STZ) was investigated in Chinese hamster
      fibroblast lines (CHO-9 and V79) in comparison to two other alkylating agents,
      methylnitrosourea (MNU) and ethylnitrosourea (ENU), using cell survival as the
      endpoint. It was found that V79 cells were far more resistant to methylation
      induced by STZ and MNU than CHO-9 cells (20 and four times, respectively) but
      equally sensitive to the ethylating agent ENU. The extent of STZ-induced DNA
      methylation was estimated by analyzing the extent of O6-metG and N7-metG adducts
      in the DNA of treated cells through high-performance liquid chromatography (HPLC)
      with electrochemical detection. The number of adducts as well the efficiencies of
      their removal from the DNA were similar in both cell lines. The response of these
      cells to the presence of DNA damage was evaluated by analysis of STZ effects on
      DNA replication and cell cycle progression. Measurement of [3H]-thymidine
      incorporation showed a similar pattern of response at the level of inhibition of
      DNA synthesis in both cell lines. However, analysis of metaphase cells 36 hr
      after STZ exposure showed an accumulation of cells in the second cycle in the CHO
      9 line, indicating induction of a cell cycle arrest. Only a slight effect was
      observed on cell cycle progression in V79 cells, indicating that the methylation
      resistance of these cells could be related to their ability to progress through
      the cell cycle despite the presence of DNA lesions.

PMID- 7641711
TI  - Structure-mutagenicity relationships of four amino-imidazonaphthyridines and
      imidazoquinolines.
AB  - We tested four isomeric imidazonaphthyridines and one imidazoquinoline compound
      for mutagenic activity in the Ames/Salmonella mutagenicity assay, using strain
      TA98 and strain YG1024, an analogue of strain TA98 with elevated O
      acetyltransferase levels. Their potency was related to calculated electronic
      parameters. Five compounds with a linear arrangement of 3 rings showed a positive
      response in strain YG1024. Compound 2 (1-methylimidazo[4,5-b][1,7]naphthyridin-2
      amine) is the most mutagenic in both strains, giving specific activities of about
      200 and 30 revertants per microgram in strains YG1024 and TA98, respectively.
      Three of the compounds were weak mutagens, giving a positive dose-response only
      in strain YG1024, with 3-5 revertants per microgram. A higher response of all
      five compounds in strain YG1024 as opposed to TA98 indicates that they require O
      acetyltransferase activity for their metabolism. Mutagenic potencies in strain
      YG1024 were positively correlated to the energy of the LUMO (lowest unoccupied
      molecular orbital) of the nitrenium ion.

PMID- 7641712
TI  - Role of classical nitroreductase and O-acetyltransferase on the mutagenicity of
      nifurtimox and eight derivatives in Salmonella typhimurium.
AB  - This study investigates the mutagenicity of nifurtimox (NFX) and eight analogues
      in Salmonella typhimurium indicator strains that possess different levels of
      classical nitroreductase or O-acetyltransferase activities. The NFX analogues
      tested replace the 3-methyl-4-yl-tetrahydro-1,4-thiazine-1,1-dioxide group of the
      parent compound with the following other groups: indazol-1-yl (1G); pyrazol-1-yl
      (1B); benzimidazol-1-yl (1E); 1,2,4-triazol-4-yl (1D); 1-methyl-3-methylthio
      1,2,4-triazol-4-yl-5-thione (1I); 3,5-bis(methylthio)-1,2,4-triazol-4-yl (1H); 1
      adamantyl (ADA); and 4,6-diphenylpyridin-1-yl-2-one (1K). In the genetic
      backgrounds of the standard Ames tester strains TA98 and TA100, these bacteria
      combine the L-arabinose resistance forward mutation assay (Ara test) with a
      deficiency or overproduction of either nitroreduction or O-acetylation. The Ara
      test revealed, in agreement with previous findings, important differences between
      TA98 and TA100 and demonstrated, moreover, that these genetic differences are of
      significance in mutagenicity testing with nitrofuran compounds. The Ara test also
      indicated dissimilarities between the metabolic activation of NFX and its
      analogues, these compounds being classified in three different groups according
      to their mutagenicity toward strain BA14 (genetic background of TA98) and its
      derivatives. The first group included analogues (1G, 1E, 1I, and ADA) that showed
      similar mutagenic potency in all bacterial strains. These compounds are
      considered not to be substrates for both classical nitroreductase and O
      acetyltransferase. The second group included compounds (analogues 1B and 1K, and
      the reference drug NFX) with increased mutagenicity toward the strain
      overproducing the classical nitroreductase, and/or reduced mutagenicity toward
      the corresponding deficient bacteria. These compounds are considered to be
      activated by the classical nitroreductase. The third group (analogues 1D and 1H)
      was activated by bacterial O-acetyltransferase, and consequently showed increased
      and decreased mutagenicity with the particular overproducer or deficient
      bacterial strain, as compared to their isogenic parentals. Previous reports have
      pointed out interest in NFX analogue 1H as a promising candidate for the
      replacement of NFX. The present study further enhances the putative interest of
      compound 1H, based on the different metabolic activation pathway exhibited by
      this analogue as compared to the parental drug, NFX.

PMID- 7641713
TI  - Relative sensitivity of the endogenous hprt gene and lacI transgene in ENU
      treated Big Blue B6C3F1 mice.
AB  - Three-week-old Big Blue (BB) B6C3F1 mice were given a single i.p. injection of
      ENU. Three weeks later, splenic T cells were isolated from each animal by ficoll
      gradient centrifugation and divided into two samples. One sample was cultured to
      measure hprt- mutation and the other was used to extract DNA for lacI- analysis.
      T cells from BB mice exposed to 0, 4.5, 13.5, and 40 mg ENU/kg (9 or 10 animals
      per group) displayed dose-related increases in the frequency of both hprt- and
      lacI- mutations. Within each treatment group, the ENU-induced mutation frequency
      (average observed mutation frequency minus average control frequency) was
      remarkably similar at the two loci. This suggests that treatments that increase
      mutation frequency at the endogenous hprt gene also produce similar incremental
      increases at the BB lacI transgene. However, because of the ten-fold higher
      spontaneous mutation rate at lacI, the fold-increase over background produced by
      ENU at this locus was significantly less than the fold-increase produced at hprt.
      For example, the 4.5 mg ENU/kg treatment produced a 5.2-fold increase above
      background at hprt (P = 0.001), whereas only a 1.5-fold increase was produced at
      lacI (P = 0.140). Consequently, mutagenic insults that produce up to a fivefold
      increase in mutation frequency at an endogenous locus may be difficult to detect
      at the lacI transgene. Finally, the ENU-induced response at hprt in BB mice was
      identical to that in generic B6C3F1 mice, suggesting that there are no inherent
      differences between transgenic and normal mice in their response to this
      mutagenic agent.

PMID- 7641714
TI  - A review of molecular genetics for the anaesthetist.

PMID- 7641715
TI  - Anaesthesia and resuscitation at altitude.

PMID- 7641716
TI  - Comparison of tramadol with morphine for post-operative pain following abdominal
      surgery.
AB  - In a multi-centre, double-blind, randomized study involving 523 patients, the
      analgesic efficacy of tramadol was compared to that of morphine given in repeated
      intravenous boluses as required to control post-operative pain following
      abdominal surgery over 24 h. Intravenous administration of the study analgesic
      started as soon as the patient reported pain. Patients received an initial dose
      (either tramadol 100 mg or morphine 5 mg) and, if necessary, repeat doses of
      tramadol 50 mg or morphine 5 mg could be given on demand over the first 90 min.
      Further doses up to a total of tramadol 400 mg or morphine 40 mg could then be
      given after 90 min up to 24 h after the first dose of study medication. The
      primary efficacy parameter was the responder rate (no or slight pain) within the
      first 90 min of treatment. Whilst responder rates reached 72.6% with tramadol and
      81.2% with morphine, the treatments were statistically equivalent and the
      observed difference in the responder rates between the groups was within the
      predefined range of +/- 10%. Mean cumulative doses received by treatment
      responders amounted to 188.2 mg within the first 1.5 h and 157.1 mg during the
      subsequent 22.5 h in the tramadol group and 13.9 and 18.4 mg, respectively, in
      the morphine group. A high incidence of gastrointestinal adverse events were
      observed with both treatments mostly consisting of mild nausea, dry mouth,
      vomiting, dyspepsia and hiccups.

PMID- 7641717
TI  - Microcatheter continuous spinal anaesthesia in the post-operative period: a
      prospective study of its effectiveness and complications.
AB  - One hundred patients (aged 22-86 years, mean 62.5), undergoing lower limb
      orthopaedic surgery, received continuous spinal anaesthesia using a 28 s.w.g.
      catheter inserted through a 22 s.w.g. Quincke needle. Post-operative pain relief
      was provided by bolus injections of 1-2.5 mL 4 h-1 of plain 0.25% bupivacaine.
      The mean dose of bupivacaine required for sufficient pain relief in 93% of
      patients was 1.6 +/- 0.2 (1.3-1.9) mL 4 h-1. The highest dose was needed between
      4 and 8 h post-operatively. No dependence of dose on age or type of operation was
      found. Technical problems with the microcatheter occurred in 12%. The most
      frequent complaint was post-operative backache (12%). Only one patient suffered
      from post-dural puncture headache on the day after surgery. There was no
      microbiological contamination of the catheter tips after removal. In the post
      operative interview, 89% of the patients were completely satisfied with CSA; 91%
      would prefer this technique to general anaesthesia.

PMID- 7641718
TI  - Dexmedetomidine, a potent alpha 2-agonist, does not affect neuronal damage
      following severe forebrain ischaemia in the rat.
AB  - Central sympathetic activation with increased release of noradrenaline occurs
      during cerebral ischaemia, but it is not certain how the increased sympathetic
      activity affects neuronal damage. We have studied the effect of dexmedetomidine,
      a potent alpha 2-adrenergic receptor agonist that reduces the central release of
      noradrenaline, on neuronal damage after 10 min of severe forebrain ischaemia in
      the rat. Ischaemia was achieved by bilateral carotid artery occlusion combined
      with bleeding to a mean arterial pressure of 50 mmHg. The post-ischaemic neuronal
      damage was most pronounced in the hippocampal CA1 region (median percentage of
      necrotic cells 36% (11-69%) and 42% (11-68%) in the dexmedetomidine and vehicle
      groups, respectively) and in the subiculum. The reticular thalamic nucleus was
      moderately damaged in all but one rat, while the rest of the thalamus was almost
      spared. Most rats had mild to moderate damage in cortex and caudoputamen.
      Dexmedetomidine did not affect the neuronal outcome in this model.

PMID- 7641719
TI  - Topical anaesthesia for the insertion of nasogastric tubes.
AB  - The effect of topical anaesthesia on the discomfort caused by insertion of
      nasogastric tubes in conscious patients was assessed. An intra-nasal spray of 4%
      lignocaine significantly reduced the distress experienced without any increase in
      difficulty (P < 0.01).

PMID- 7641720
TI  - A comparison of propofol and isoflurane anaesthesia: the need for ephedrine and
      glycopyrrolate.
AB  - Sixty patients, ASA I-III, presenting for elective colonic surgery were studied
      to assess the stability of blood pressure and heart rate during anaesthesia with
      three equally potent anaesthetic techniques. Patients in group I (n = 20)
      received thiopentone induction, isoflurane and nitrous oxide; patients in group
      II (n = 20) received total intravenous anaesthesia with propofol; and patients in
      group III (n = 20) received intravenous propofol supplemented with nitrous oxide.
      Fentanyl and vecuronium were used in all three groups. The depth of anaesthesia
      was judged on clinical signs of adequate anaesthesia. Episodes of bradycardia
      (heart rate < 50 beats min-1), tachycardia (heart rate > 90 beats min-1),
      hypotension (mean arterial pressure > or = 30% below pre-operative blood
      pressure) or hypertension (mean arterial pressure > 30%, or systolic blood
      pressure > 15 mmHg, above pre-operative value) were recorded when lasting > 5
      min. Any use of ephedrine or glycopyrrolate given to correct hypotension or
      bradycardia was documented: In group II, significantly more patients were given
      ephedrine (P < 0.01) to treat hypotension. The drug was administered after
      intubation but before skin incision in the majority of cases (9/11).
      Glycopyrrolate was given to significantly more patients in group III (P < 0.025)
      to treat bradycardia, and in 21 of a total of 34 patients given glycopyrrolate it
      was administered before surgery. With the use of these additional drugs, there
      were no differences in the number of patients with 5 min episodes of hypotension,
      hypertension, tachycardia or bradycardia.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7641721
TI  - Quantitation of the enflurane-sparing effect of alfentanil during general
      surgery.
AB  - The authors quantitated the enflurane-sparing effect of alfentanil during N2O/O2
      anaesthesia in 50 patients undergoing body surface surgery and in 50 patients
      undergoing upper abdominal surgery. Patients were assigned to one of five
      treatment regimens (10 patients each group, double-blind administration) as
      follows: placebo bolus followed by placebo infusion (group I); or alfentanil
      bolus (30 micrograms kg-1) followed by infusion of placebo (group II) or
      alfentanil, at the rate of 10 (group III), 20 (group IV), or 40 (group V)
      micrograms kg-1 h-1. Anaesthesia was induced with thiopentone and vecuronium, and
      neuromuscular block was kept at 85-90% by continuous infusion of vecuronium.
      Increases in spontaneous electromyographic activity of neck muscles (NEMG) and in
      systolic blood pressure (SBP) served as criteria of inadequate anaesthesia. When
      such increases occurred, enflurane was given in 0.2% steps (end-tidal
      concentration) of 5 min each, until the increases were suppressed. The
      relationship between increases in NEMG and increases in SBP was inconsistent:
      only 10% of the increases occurred simultaneously. With alfentanil, the
      consumption of enflurane decreased by as much as 70% (P < 0.001) during
      superficial surgery and 50% (P < 0.05) during abdominal surgery.

PMID- 7641722
TI  - Onset of neuromuscular block during total intravenous anaesthesia: effects of
      ketamine compared with alfentanil.
AB  - Anaesthesia was induced in 30 ASA I patients by propofol titrated at 100 mg min-1
      to loss of verbal contact, and maintained by infusion of propofol at 10 mg kg-1 h
      1 with 100% oxygen. According to randomization, either alfentanil 30 micrograms
      kg-1 ketamine 1.5 mg kg-1, or 0.9% sodium chloride was injected over 20 s,
      followed 1 min later by vecuronium 0.08 mg kg-1. Mean arterial pressure and heart
      rate were measured before and after induction, and 1 and 2 min after analgesic or
      saline. Onset of neuromuscular block was measured by the evoked hypothenar
      electromyographic response to train-of-four supra-maximal stimuli at 0.1 Hz.
      There were significant haemodynamic differences between groups, but mean (SD)
      times to reduction of T1/control ratios below 95% were 114 (28.0), 106 (19.0) and
      128 (34.3) s (P = 0.2, ANOVA). Supplementation of propofol anaesthesia with
      alfentanil or ketamine does not appear to influence the onset time of vecuronium.

PMID- 7641723
TI  - Speed of onset of analgesic effect of intravenous ketorolac compared to morphine
      and placebo.
AB  - The speed of onset of analgesia following intravenous ketorolac, morphine and
      placebo was investigated in a single-dose, double-blind, randomized, parallel
      group study of 105 patients. The onset of analgesia was defined as the time at
      which the pain intensity score reached 50% of the baseline score in 25% of
      patients. Post-operative patients with moderate or severe pain were dosed and
      followed for 1 h. Pain reduction by at least 50% occurred in 25% of patients
      within 40 min (placebo), 15 min (morphine 5 mg), 6 min (morphine 10 mg) and 20
      min (ketorolac 10 mg). The pain reduction time for morphine (10 mg) was
      significantly shorter than that for ketorolac (P = 0.01) or placebo (P < 0.01).

PMID- 7641724
TI  - Anaesthesia for urological endoscopic procedures in adult outpatients.
AB  - The aim of this study was to establish whether propofol in combination with
      fentanyl or ketamine provides a good quality of anaesthesia and recovery time in
      urological endoscopic outpatient surgery. Sixty patients (ASA I-II) were assigned
      randomly to receive either 2.5 micrograms kg-1 fentanyl or 1 mg kg-1 ketamine. In
      both groups anaesthesia was induced with propofol 1.5 mg kg-1 and maintained with
      7 mg kg-1 h-1. Patients breathed nitrous oxide and oxygen 3:2 spontaneously.
      Cardiovascular parameters were more stable after ketamine. The most important
      side effect was the presence of apnoea lasting longer than 60 s in 14 patients
      receiving fentanyl. The time to establish alertness was shorter in the ketamine
      group, who also had a better (P < 0.05) as well as post-anaesthetic recovery room
      score.

PMID- 7641725
TI  - Failure of anaesthesia with etomidate.
AB  - A case of failure of etomidate anaesthesia in a patient with chronic renal
      failure and multiple myeloma is described. Adequate serum levels of etomidate
      were confirmed. High levels of serum light chains were noted, and may be
      associated with the lack of action of etomidate.

PMID- 7641726
TI  - Drosophila gp210, an invertebrate nuclear pore complex glycoprotein.
AB  - Monoclonal antibodies were used to localize the putative Drosophila homolog of
      mammalian nuclear pore complex glycoprotein, gp210, to Drosophila nuclear pore
      complexes. Both immunofluorescence and immunoelectron microscopy were performed.
      To the best of our knowledge, this establishes Drosophila gp210 as the first
      invertebrate gp210 homolog. Results of developmental studies demonstrated that
      like nuclear lamin and DNA topoisomerase II, gp210 is found abundantly in
      nonnuclear form early in embryogenesis where it presumably fuels the rapid
      assembly of new nuclei. Unlike thse other two proteins, gp210 levels are maximal
      early after wich they decrease significantly; in addition, nonnuclear gp210 found
      in early Drosophila embryos is apparently associated with membrane vesicles.
      These results have implications for understanding the regulation of higher
      eukaryotic nuclear pore complex behavior through development as well as for
      determining gp210 function genetically.

PMID- 7641727
TI  - Immunolocalization of secretogranin II and insulin in a nerve growth factor
      differentiated insulinoma cell line.
AB  - RINm5F, a rat insulin-secreting pancreatic cell line, responds to nerve growth
      factor (NGF) by extending neurite-like processes. Secretogranin II (SgII), a
      marker of neuroendocrine secretory organelles, has recently been found to be a
      good marker of neuronal differentiation in both human neuroblastoma and rat
      pheochromocytoma cells. The present paper reports the results obtained from
      immunocytochemical studies, which show that NGF increases the expression of SgII
      immunolabeled organelles in RINm5F cells. We also demonstrate that NGF increases
      the expression of insulin and that SgII and insulin are predominantly, but not
      always, colocalized. These results suggest that this insulinoma cell line may be
      a good model for studying the role of SgII in neuroendocrine secretion
      mechanisms.

PMID- 7641729
TI  - Molecular characterization of a novel atrial-specific myosin heavy-chain gene
      expressed in the chick embryo.
AB  - A 1.2 kb fragment of a myosin heavy-chain (MHC) gene was isolated from the
      complementary DNA (cDNA) library derived from embryonic day 15 (E15), Hamburger
      and Hamilton (H.H) stage 41 chick embryonic ventricle, using a fragment of human
      beta-cardiac MHC cDNA as a probe. DNA sequence analysis determined that the gene
      (CCSV2) encoded the amino acid sequence of the rod portion (part of S2 and light
      meromyosin) of the chick atrial-specific MHC gene. The nucleotide sequence of
      CCSV2 was slightly different (90% homologous) from a previously reported atrial
      specific MHC (AMHC1) expressed in chick embryo. Northern blot analysis, with the
      CCSV2 fragment (1.2 kb) used as a probe, showed that the gene is expressed
      intensively in the developing chick atrial muscle, but weakly in the ventricle
      and pectoralis muscle. S1-nuclease mapping analysis, with CCSV2 used as a probe,
      demonstrated a fully protected fragment in the atrium and ventricle. In this
      study, no intensive signal of a partially protected fragment was detected in the
      atrium. On the other hand, not only a fully protected fragment, but also four
      partially protected fragments were observed in the pectoralis muscle. Whole-mount
      in situ hybridization was performed in developing chick heart at H.H. stages 19,
      21 and 30. The hybridization signal was intensive in the primitive atrium (H.H.
      stages 19 and 21) and in the atrial appendages derived from the primitive atrium
      (H.H. stage 30). Weak signals were detected in the primitive ventricle (H.H.
      stages 19 and 21), the ventricle (H.H. stage 30) and in the somites (H.H. stages
      19 and 21).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7641728
TI  - Lipopolysaccharide-stimulated exocytosis of nonself recognition protein from
      insect hemocytes depend on protein tyrosine phosphorylation.
AB  - Insect hemocytes (blood cells) synthesize the major nonself recognition protein
      (47 kDa) during 3rd instar larvae (V.J. Marmaras, S. Tsakas, Dev. Biol. 129, 294
      303 (1988)). In this study we show the presence of the 47 kDa protein in
      plasmatocytes (main hemocyte type) and prohemocytes. In plasmatocytes this
      protein appears to be localized both in vesicles and in the cell surface. The
      cell surface-associated 47 kDa protein was released from membrane fraction by 1 M
      NaCl, indicating that it is not tightly bound. Bacterial lipopolysaccharide (LPS)
      can function on isolated hemocytes from Ceratitis capitata larvae, inducing their
      spreading and degranulation. During degranulation (exocytosis) the plasmatocytes
      release the 47 kDa protein, among others. This protein could not be normally
      traced in serum, nor is it released by basal secretion. The secretion of the 47
      kDa protein was found to be LPS-dependent, whereas its presence on plasmatocyte
      surface is LPS independent. LPS-stimulated exocytosis of the 47 kDa protein
      appears to be dependent on protein tyrosine phosphorylation. We have now
      demonstrated that LPS increases tyrosine phosphorylation of 19 and 22 kDa
      polypeptides in C. capitata hemocytes. Inhibition of the LPS-induced tyrosine
      phosphorylation mediated by tyrosine kinase inhibitor, genistein, was accompanied
      by the inhibition of the secretion of the 47 kDa protein. These results support
      the hypothesis that tyrosine protein phosphorylation is a signal reaction in
      hemocytes after LPS exposure. These LPS responses of insect plasmatocytes show
      strong similarities to mammalian macrophages (S. Weinstein et al., J. Immunol.
      151, 3829-3838 (1993)). In a model we propose that the LPS-independent cell
      surface-associated 47 kDa protein is responsible for the phagocytosis and for the
      formation of nodules and capsules, whereas the LPS-dependent secreting
      counterpart is responsible for the extracellular killing of bacteria.

PMID- 7641730
TI  - Interphase cells of the centric diatom, Thalassiosira fluviatilis, lack
      detyrosinated, nontyrosinatable and acetylated tubulin.
AB  - Within eukaryotic cells tubulin generally exists in protein families composed of
      closely related isoforms generated either by differential gene transcription or
      by posttranscriptional and posttranslational mechanisms. In this study,
      immunological approaches were used to examine the contribution of
      posttranslational modifications to tubulin heterogeneity in a centric diatom,
      Thalassiosira fluviatilis, and to show the spatial distribution of microtubules
      in these cells during their interphase. After blotting to nitrocellulose, tubulin
      in cell-free homogenates of T. fluviatilis was recognized by several general
      tubulin antibodies including one to the tyrosinated isoform, but not by
      antibodies to detyrosinated, nontyrosinatable nor acetylated tubulins.
      Immunofluorescent staining of methanol-fixed cells revealed a net-like reticulum
      of microtubules originating at or near the cell nucleus. For all antibodies,
      except one (TU-01), results obtained by immunofluorescent experiments corrobated
      the analysis of blotted tubulins. Furthermore, microtubules exhibited
      differential staining patterns corresponding to the intensity of antibody
      reactivity on blots. Antibody to detyrosinated tubulin, as well as TU-01, yielded
      a spotty pattern of fluorescence on chloroplasts. Microtubules in T. fluviatilis
      support normal cell function in the absence of detectable amounts of three common
      posttranslationally modified tubulins, perhaps due to the rigid silica frustule
      which maintains shape and to the absence of flagella in interphase cells.

PMID- 7641731
TI  - Ultrastructural, immunocytochemical and stereological investigation of
      hepatocytes in a patient with the mutation of the ornithine transcarbamylase
      gene.
AB  - We studied a male newborn suffering from deficiency of ornithine transcarbamylase
      (OTC) that is due to a G-to-A substitution in codon 269 of the OTC gene. This
      study intends to define the cell biological mechanisms in this naturally
      occurring OTC mutation which may explain the mild clinical course in spite of the
      very low residual enzyme activity. Using immunogold labeling of thawed thin
      frozen sections of liver from this patient and a control liver, we analyzed the
      quantitative distribution of several mitochondrial proteins in the cytosol and
      the mitochondria of hepatocytes. In addition, the absolute volumes and surface
      densities of mitochondria and peroxisomes were determined. Our results show that
      the absolute volume of mitochondria in the patient's hepatocytes was increased to
      141% (P < 0.001) without any change in the surface density indicating an
      increased number of mitochondria. In the patient's hepatocytes the peroxisomes
      were increased in size but not in number. The concentration of OTC was elevated
      in the cytosol (P < 0.001) and to a lesser extent in mitochondria (P < 0.01) of
      the patient's hepatocytes thus indicating a doubling of OTC relative to control
      liver cells. The quantity of OTC in mitochondria was 63% higher in diseased liver
      cells. By conventional thin section electron microscopy, mitochondria-like
      structures with poorly defined cristae and an electron-dense matrix were observed
      in the cytoplasm of the diseased hepatocytes. By immunoelectron microscopy, they
      contained the cytochrome c oxidase II subunit as well as DNA but lacked OTC,
      carbamylphosphate synthetase, F1-ATPase beta subunit and catalase. Thus it
      appears that these structures represent defective and probably degenerating
      mitochondria. Our data indicate that the reduced enzyme activity of the mutant
      OTC is partly compensated by an increased amount of enzyme molecules in the
      cytosol as well as mitochondria combined with an increase in the biogenesis of
      mitochondria.

PMID- 7641732
TI  - Analysis of nucleocytoplasmic transport and nuclear envelope structure in yeast
      disrupted for the gene encoding the nuclear pore protein Nup1p.
AB  - Nup1p and Nsp1p are structurally related nuclear pore complex (NPC) proteins
      which contain many degenerate repeat sequences of the FSFG type in their central
      domains. To find out whether this similarity also reflects a functional overlap
      at the NPC, we analyzed delta nup1 cells in comparison to ts nsp1 cells for
      defects in nucleocytoplasmic transport. When the NUP1 gene was disrupted in two
      different laboratory yeast strains, haploid delta nup1 progeny was viable,
      showing that NUP1 is not essential for vegetative cell growth; delta nup1
      strains, however, exhibited a strongly reduced growth rate at 37 degrees C as
      compared to 23 degrees C. When analyzed by thin section electron microscopy,
      delta nup1 cells show a normal nuclear envelope morphology and the number and
      appearance of nuclear pore complexes apparently was not altered. Whereas delta
      nup1 cells grown at 37 degrees C could still accumulate a lacZ reporter protein
      carrying a nuclear localization sequence (NLS) inside the nucleus, poly(A)+ RNA
      export was significantly inhibited. Our data suggest that Nup1p which is not
      physically associated with Nsp1p, is required for efficient nucleocytoplasmic
      transport reactions.

PMID- 7641733
TI  - The oligosaccharides have an essential but indirect role in sorting gp80
      (clusterin, TRPM-2) to the apical surface of MDCK cells.

PMID- 7641734
TI  - Visualization of immunogold-labeled cytoskeletal proteins by scanning electron
      microscopy.

PMID- 7641735
TI  - Differentiation in the RD rhabdomyosarcoma cell line after electroporation.

PMID- 7641736
TI  - Dose intensity of cisplatin-based chemotherapy in epithelial ovarian carcinoma.
      An important factor affecting survival.
AB  - Forty-three patients with epithelial ovarian carcinoma, were treated by
      cyclophosphamide and cisplatin (CP) following initial laparotomy. The mean dose
      intensity (DI) and mean relative dose intensity (RDI) respectively were for
      cyclophosphamide: 166.69 mg/sqm/week and 0.67, and for cisplatin: 16.29
      mg/sqm/week and 0.65. The mean average relative dose intensity (ARDI) was 0.66.
      The three-year survival for all patients was 44.3%. The three-year survival for
      patients receiving cyclophosphamide with a RDI of more than median value was
      63.82%, while for patients receiving cyclophosphamide with a RDI of less than
      median value three-year survival was 26.3% (p < 0.02). The three-year survival
      for patients receiving cisplatin with an RDI of more than median value was
      62.01%, as compared to 24.17% for patients receiving cisplatin with a RDI of less
      than median value (p < 0.02). The three-year survival for patients receiving the
      CP regimen with an ARDI of more than median value was significantly higher than
      that for patients receiving the CP regimen with an ARDI of less than median value
      (63.82% versus 26.03%, p < 0.02). Dose intensity of cisplatin-based chemotherapy
      in epithelial ovarian carcinoma is an important factor affecting survival.

PMID- 7641737
TI  - Atypical polypoid adenomyoma of the uterus in a very old woman. Report of a case
      with immunohistochemical characterization of its stromal components and
      proliferative status.
AB  - A case of atypical polypoid adenomyoma (APA) of the uterus in an 81-year-old
      patient is reported. The tumor arose in the uterine fundus as a polypoid mass and
      measured 9 cm in its longest diameter. Its histological appearance was similar to
      that of the reported cases, i.e. presence of atypical endometrial glands and a
      cellular smooth muscle stroma. However, the patient's age was extremely advanced,
      since APA has predominantly been reported to arise in premenopausal women. APA
      has been suggested as being related to prolonged estrogenic stimulation. But the
      fact that in this case the uninvolved endometrium was absolutely atrophic,
      negated this possibility. Immunohistochemistry for alpha smooth muscle actin was
      positive diffusely in the stroma. The proliferative status of the neoplastic
      glands was assessed by immunostaining for Ki-67 antigen. About 30% of the glands
      contained Ki-67 positive nuclei, and about 3% of the nuclei were positive in the
      glands. These figures are far below those of the usual endometrial
      adenocarcinoma, strongly suggesting that the APA was benign in nature.

PMID- 7641738
TI  - Is it essential to perform complete paraaortic lymph node dissection if no
      metastases have been shown in the lower part of the aorta?
AB  - One hundred and twenty eight patients with cervical carcinoma underwent
      pretherapy staging laparotomy between the years 1991 and 1994. Adopting a
      transperitoneal approach nodal dissection was performed from the aortic
      bifurcation to the level of the renal artery. Specimens were segregated into
      those inferior to and superior to the origin of the inferior mesenteric artery
      (IMA) then sent for pathologic examination. Of the 15 histologically malign node
      samples inferior to the IMA, none were associated with neoplasia in the groups of
      node samples taken from above the IMA. Of the 5 malignant nodal samples taken
      from above the IMA, all had concurrent neoplastic changes in the specimens taken
      from below the IMA. An intraoperative complication rate of 8.7% was encountered
      in the lower nodal dissections. This was compounded by a resultant 7.7%
      complication rate with nodal dissection above the IMA. As a result of our
      findings we feel confident in omitting upper paraaortic lymph node (PALN)
      dissection in the absence of malignant findings in the inferior paraaortic lymph
      node at frozen section.

PMID- 7641739
TI  - Computed tomography and second-look surgery in ovarian cancer patients.
      Correlation, actual role and limitations of CT scan.
AB  - Computed tomography (CT scan) was performed on 58 clinically disease-free ovarian
      cancer patients. The scans were correlated with the results obtained at a
      subsequent second-look laparotomy. The sensitivity was 0.47, the specificity
      0.87, diagnostic accuracy 0.63, positive predictive value 0.84 and negative 0.53.
      Undetected microscopic disease was classified as a false-negative result.
      Sensitivity was poor for omental, mesenteric and peritoneal implants and for
      bowel infiltration, good for lymphnodal involvement and abdominal mass and
      decisively good for intrahepatic and plenic metastases of ovarian cancer. Due to
      a still high false-negative rate a normal CT scan does not provide sufficiently
      accurate diagnostic information to replace a second-look laparotomy. But on the
      other hand, due to a high specificity, the usefulness of CT can be limited to
      approximately 27% of patients, with true-positive findings, who might have been
      saved surgical reexploration. Adjunct studies such as immunoscintigraphy with
      radiolabelled monoclonal antibodies and measurement of tumor markers further
      increase its diagnostic accuracy.

PMID- 7641740
TI  - Level of c-erbB-2 oncoprotein in the homogenate of malignant and benign breast
      tumor samples.
AB  - The concentration of c-erbB-2 oncoprotein (HER-2/neu) was examined in the
      membrane fraction of 196 breast cancer and 39 benign breast specimens using a
      recently introduced ELISA-assay. The results were compared with established
      clinical and laboratory prognostic factors, 19% of all breast cancer specimens
      showed a c-erbB-2 protein level above 10 HNU/micrograms extract protein and were
      so classified as positive. Considering only the samples of primary tumors the
      rate was 21%. Surprisingly the rate was only 13.5% in the tissue samples of
      recurrent disease. Significant correlations were found between high c-erbB-2
      protein levels and the tumor diameter, the axillary lymph node status and the
      progesterone receptor status. In contrast no correlation was found with estrogen
      receptor or menopausal status. All specimens of benign tumors showed levels < 10
      HNU/micrograms extract protein and were classified as negative. The measurement
      of the c-erbB-2 protein using this ELISA assay was simple to perform and revealed
      reliable results. Nevertheless the prognostic power of the c-erbB-2 protein seems
      to be of minor relevance in comparison with established clinical and laboratory
      parameters, as the positive rates are too small in regard to the much higher
      recurrence rates of breast cancer. Probably the serum levels of this oncoprotein
      will be of greater clinical interest in the course of breast cancer.

PMID- 7641741
TI  - Clinical implication of fos and jun expressions and protein kinase activity in
      endometrial cancers.
AB  - Under the previous data of the presence of fos/jun expression via protein kinase
      C (PKC) activation by estrogen in endometrial cancer cell line (1), the following
      experiment was made on the endometrial cancer tissue of the human subject. The
      ratio of membrane/cytosol PKC activity and the level of fos/jun expression were
      significantly higher in well differentiated endometrial cancers than in those of
      moderately or poorly differentiated ones. Those two in the endometrial cancer
      were significantly higher than those in the normal counterpart. The ratio and the
      expression in normal uterine endometria of the proliferative phase were
      significantly higher than those in the secretory phase. Both in the endometria
      were significantly enhanced 1 week after the administration of estrogen. It is
      suggested that the linkage of fos/jun expression via PKC activation by estrogen
      might be exaggerated in the endometrial cancers, especially in the well
      differentiated, plausibly with the loss of the anti-estrogen effect of
      progesterone, but dedifferentiation might lose this linkage.

PMID- 7641742
TI  - Distribution of integrins and extracellular matrix proteins in vulvar squamous
      cell carcinomas.
AB  - We report the topography of integrins and some basement membrane zone (BMZ)
      proteins in normal vulvar skin and in seven cases of vulvar squamous carcinoma
      (VSC). In vulvar epidermis integrin chains alpha 2, alpha 3 and beta 1 lined the
      lateral surface of basal cells, while the heterodimer alpha 6 beta 4 was detected
      only at their basal domain. The location of alpha 6 beta 4 exactly matched BMZ
      identified by kalinin, laminin and collagen type IV. In VSC this pattern was
      subverted since both beta 1 integrins and alpha 6 beta 4 became pericellular. In
      particular, alpha 6 beta 4 lost its coherence with the residual organization of
      BMZ. In fact, BMZ components displayed their normal pattern were this was
      preserved, and so were fibronectin and tenascin in the stroma underlying the
      tumor. Furthermore, alpha 5 beta 1, the prototype fibronectin receptor that is
      not normally exposed in vulvar epidermal cells, became detectable pericellularly
      in VSC tumor cells. Alteration of integrin polarized topography appears to be
      typical of VSC cells as well as of other tumor epidermal cells. This alteration
      may be easily shown by immunohistochemistry on routinely collected frozen
      biopsies. It may then represent a tool for the early diagnosis of VSC that
      provides a quick and easy complement of traditional histology.

PMID- 7641743
TI  - Demonstration of estrogen and progesterone receptors in breast cancers with
      monoclonal antibodies. Different results with enzyme-immunoassay and
      immunohistochemical methods.
AB  - Estrogen (ER) and progesterone receptors (PR) were measured in 120 breast cancer
      biopsies using the same tissue block and the same monoclonal antibody either
      immunohistochemically on frozen sections or quantitative by means of an enzyme
      immunoassay (EIA) on the cytosol-fraction of a tumor homogenate. The
      immunohistochemical staining was performed by a standard PAP-method and the
      samples were classified according to the "immuno-reactive score" (IRS). IRS
      values > = 2 were regarded as receptor-positive; a cut-off-value of 15 fmol/mg
      protein was chosen for the EIA-test. In 90.8% of cases the findings of
      immunohistochemical and biochemical methods were concordant when only receptor
      positivity or -negativity was regarded. Thus the results were discordant in 9.2%.
      Immunohistochemically positive and biochemically negative findings were observed
      more often (8.2% for the ER and 5.8% for the PR) than vice versa (0.8% for the ER
      and 3.3% for the PR). In all cases of discordant findings the relevant
      histological and immunohistochemical preparations were reevaluated. In total,
      there were 5 cases with a positive biochemical result which were classified as
      receptor-negative by immunohistochemistry. Of these, 3 had borderline findings by
      EIA together with a massive inflammatory infiltration. The other 2 cases must be
      interpreted as technical problems with the immunohistochemical staining. In 17
      cases with a biochemically negative result receptor-positive cancer cells could
      be demonstrated by immunohistochemistry. In 13 of these 17 cases only a small
      fraction of tumor cells showed a positive reaction. Furthermore all these cases
      were rather acellular and partially necrotic. So the negative results of the
      enzyme immunoassay can be explained by a low concentration of receptor positive
      cells in the biopsy specimen or the measurements of necrotic tissue areas. It can
      be concluded that immunohistochemical receptor analysis is superior to methods
      using tumor-homogenates. The prognostic and predictive superiority of the
      immunohistochemical method is in accordance with published data. However, for
      immunohistochemical staining high internal and external quality standards must be
      applied as for similar laboratory procedures.

PMID- 7641744
TI  - A study comparing LETZ and CO2 laser treatment for cervical intra epithelial
      neoplasia with and without associated human papilloma virus.
AB  - OBJECTIVE: To evaluate the recurrence of cervical intraepithelial neoplasia (CIN)
      following treatment with CO2 laser ablation and loop excision of the
      transformation zone (LETZ) and its correlation with the presence of HPV. METHODS:
      Six hundred and forty two women diagnosed as having CIN were treated either by
      CO2 laser (318) or LETZ (324) and were followed up for a minimum of 12 months.
      Recurrence rates in each group were evaluated and correlated with the presence or
      absence of HPV prior to treatment. RESULTS: There was a considerably higher rate
      of recurrent disease observed after treatment with laser ablation than LETZ (9%
      after LETZ and 37% after laser ablation) p < 0.001. Two hundred and sixty four
      women (41%) had HPV infection prior to treatment and 29% of these required
      further treatment for recurrent CIN whereas there were only 11% of women out of
      the 374 who had no evidence of HPV infection p < 0.001. CONCLUSION: Treatment of
      CIN in the presence of HPV infection results in higher failure rates and this is
      significantly increased when the treatment is by laser ablation rather than by
      LETZ.

PMID- 7641745
TI  - Ondansetron in chemotherapy-induced emesis. Our experience.
AB  - Chemotherapy-induced nausea and vomiting is one of the major side effects of
      antiblastic treatment in cancer patients, seriously affecting both the compliance
      of the patient to therapy and his or her quality of life. OBJECTIVE: The Authors
      present their experience in the use of ondansetron in 47 patients receiving 186
      cycles of chemotherapy for breast or genital neoplasms. RESULTS: Successful
      control of vomiting was achieved in the first 24 hours, in 74% of the cycles
      containing cisplatin and 82% of the cycles without cisplatin, if ondansetron was
      used. On delayed vomiting the difference in results was not as striking as on
      acute emesis. CONCLUSIONS: The major side effects with ondansetron were headaches
      (42.4%) and constipation (48.9%). As expected, no extra-pyramidal symptoms were
      observed in this group, versus 13.3% of the patients treated with metoclopramide.

PMID- 7641746
TI  - The issue of the decade: hormesis.

PMID- 7641747
TI  - A correlative study of ultrasound calcaneal and dual-energy X-ray absorptiometry
      bone measurements of the lumbar spine and femur in 1000 women.
AB  - The objectives of the study were firstly to determine the accuracy of ultrasound
      calcaneal measurements in the prediction of bone mineral density determinations
      with dual-energy X-ray absorptiometry (DXA) of the lumbar spine (LS), femoral
      neck (FN), and Ward's triangle (FW) in a mixed population of 1000 women, unsorted
      as to diagnosis, and secondly to determine the accuracy of the various site
      specific measurements in predicting each other. Ultrasound measurements
      [stiffness, speed of sound (SOS) and broadband ultrasound attenuation (BUA)] were
      made with the Lunar Achilles device, and the bone mineral density (BMD) of the
      LS, FN and FW were determined with the Lunar DPX. The data were analyzed for
      correlation, sensitivity, specificity, and accuracy of various paired sites. The
      coefficients of correlation of the young adult t-scores in the total group
      between calcaneal stiffness and BMDs of the LS, FN, and FW varied between 0.53
      and 0.60. Coefficients for LS versus FN and FW were 0.70 and 0.62, respectively.
      A comparison of SOS and BUA values obtained at the calcaneus with BMDs of the LS,
      FN and FW yielded correlation coefficients that varied from 0.54 to 0.56. The
      general accuracy of prediction of one site by another ranged from 64.2% to 74.4%,
      where normality was defined as a t-score > -2. It is concluded that no site can
      predict the status of another site with sufficiently high accuracy to be
      clinically useful. The role of ultrasound transmission in bone as a predictor of
      fracture risk is theoretically promising, but has yet to be proved by a long term
      prospective study.

PMID- 7641748
TI  - Anteroposterior versus lateral bone mineral density of spine assessed by dual X
      ray absorptiometry.
AB  - Recently, it has been suggested that lateral (LAT) spine bone mass measurements
      by absorptiometry may be more sensitive for detecting bone loss than the standard
      anteroposterior (AP) projection. The aim of this study was to evaluate the
      precision of LAT spine dual-energy X-ray absorptiometry (DEXA) and its diagnostic
      sensitivity. A group of 1554 subjects with no risk factors that might affect bone
      metabolism and 185 osteoporotic patients with vertebral fractures were studied.
      Bone mineral density (BMD) was measured in the lumbar spine (standard AP and LAT
      projections) and proximal femur with a DEXA absorptiometer. The precision of the
      measurements was assessed in 15 volunteers. Diagnostic sensitivity was evaluated
      by the Z-score method. Comparing young people and the elderly, spine bone loss in
      the latter was similar for AP and LAT projections, when it was evaluated in
      absolute values (glcm2). However, when it was evaluated in percentage terms, bone
      loss was about twice as high in the LAT projection. LAT spine BMD correlated
      significantly with all the other areas assessed. The best correlation was found
      with the standard AP projection (r = 0.67, P < 0.0001). The precision in the LAT
      projection was found to be within an acceptable range (1.6% in normal subjects,
      2% in osteoporotic patients), even though it was about twice that obtained in the
      AP projection. Diagnostic sensitivity was also better with the AP projection. It
      is concluded that LAT spine BMD measurements can be assessed with acceptable
      precision although it is about twice as high as for AP spine
      measurements.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7641749
TI  - Cerebellar diaschisis in pontine infarctions: a report of five cases.
AB  - We evaluate regional cerebral and cerebellar perfusion to prove the occurrence
      and follow the persistence of crossed cerebellar diaschisis in infratentorial
      pontine infarction. Six consecutive patients exhibiting mild hemiparetic symptoms
      or a heavy feeling in the head (mean age 65 years; four women, two men) and
      diagnosed as having pontine infarction by magnetic resonance imaging were
      subjected to evaluation. Lesions due to infarction were located at the upper
      basis pontis in five patients and the upper tegmentum pontis in one, and medially
      at the paramedian portion in four and laterally in two. Regional cerebral and
      cerebellar perfusion was evaluated semiquantitatively by iodine-123 N-isopropyl-p
      iodoamphetamine (IMP) single-photon emission tomography (SPET); this was done
      during the acute stage in five cases (mean time after onset: 0.7 months) and
      during the chronic stage in three (mean time after onset: 14.8 months). Four
      patients had two examinations during their clinical courses. For semiquantitative
      evaluation of perfusion, an asymmetry index was calculated for each region of
      interest, set symmetrically in regions of the cerebral cortex and cerebellum in
      both hemispheres. Significant asymmetry (P < 0.01) in cerebellar perfusion, which
      was reduced in the contralateral (n = 4) or ipsilateral (n = 1) cerebellar
      hemisphere, was demonstrated semiquantitatively in four cases during the acute
      stage and in one during the chronic stage, as compared with normal controls (n =
      5, mean age 61 years). This asymmetry continued to the chronic stage (6.5 and
      33.0 months) in two cases, while no patient showed any significant asymmetries in
      cerebral perfusion in any region of interest in either SPET study.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7641750
TI  - Quantitative studies of monoclonal antibody targeting to disialoganglioside GD2
      in human brain tumors.
AB  - Iodine-131 3F8, a murine IgG3 monoclonal antibody that targets to GD2-bearing
      tumors, was administered intravenously to 12 patients with brain tumors. Six
      patients received 2 mCi (0.74 Bq) of 131I-3F8, five patients 10 mCi (3.7 Bq)/1.73
      m2 of 131I-3F8, and one patient 2.6 mCi (0.96 Bq) of 124I-3F8, with no side
      effects. Nine of 11 malignant gliomas and the single metastatic melanoma showed
      antibody localization, with the best tumor delineation on single-photon emission
      tomography (SPET) following 10 mCi (3.7 Bq)/1.73 m2 dose. No nonspecific uptake
      in the normal craniospinal axis was detected. There was no difference in the
      pharmacokinetics of low-dose versus the higher-dose antibody groups; plasma and
      total-body half-lives were 18 h and 49 h, respectively. Surgical sampling and
      time-activity curves based on quantitative imaging showed peak uptake in high
      grade glioma at 39 h, with a half-life of 62 h. Tumor uptake at time of surgery
      averaged 3.5 x 10(-3) %ID/g and peak activity by the conjugate view method
      averaged 9.2 x 10(-3) %ID/g (3.5-17.8). Mean radiation absorption dose was 3.9
      rad per mCi injected (range 0.7-9.6) or 10.5 cGy/Bq (range 1.9-26). There was
      agreement on positive sites when immunoscintigraphy was compared with technetium
      99m glucoheptonate/diethylene triamine penta-acetic acid planar imaging, thallium
      201 SPET, and fluorine-18 fluorodeoxyglucose positron emission tomography. Taken
      together, these data suggest that quantitative estimates of antibody targeting to
      intracranial tumors can be made using the modified conjugate view method.

PMID- 7641751
TI  - Technetium-99m HMPAO SPET in acute supratentorial ischaemic infarction,
      expressing deficits as millilitre of zero perfusion.
AB  - A comparative interim analysis was performed of clinical parameters, computed
      tomographic (CT) scan results and technetium-99m hexamethylpropylene amine oxime
      single-photon emission tomography (SPET) findings obtained within 12 h of acute
      supratentorial ischaemic infarction. First, the applicability for SPET
      semiquantification in this study of the "method of Mountz", simultaneously
      accounting for extent and degrees of hypoperfusion by expressing deficits as
      millilitre of zero perfusion, was considered. Next, the relative contributions of
      perfusion SPET and CT scan in the acute stage of ischaemic infarction were
      compared in 27 patients (mean age 68.8 years). Finally, the correlation of SPET
      lesions with clinical parameters at onset was evaluated. The method of Mountz
      represents a workable, accurate virtual parameter, with the assumption that the
      contralateral brain region remains uninvolved. Interobserver reproducibility in
      12 SPET studies, with lesions varying between 6 and 369 cc, showed a correlation
      coefficient r of 0.99. In practice, because of inconstant distribution of
      activities in the brain, the method can only be applied slice by slice and not on
      the total global volume. While the mean delay since the onset of symptomatology
      was approximately 7 h for both SPET and CT scan, SPET showed lesions concordant
      with the clinical neurological findings in 100% and CT scan in only 48%. One
      could hypothesize that SPET examinations performed later would show larger
      functional defects, because of the development of additional functional changes
      secondary to biochemical alterations. However, in this regard no statistically
      significant differences were found between two subproups, taking the median of
      delay before SPET examination as cut-off.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7641752
TI  - Evaluation of tumour metabolism and multidrug resistance in patients with treated
      malignant lymphomas.
AB  - The management of patients with treated malignant lymphomas requires functional
      methods to differentiate a residual soft tissue mass. Patients with treated
      Hodgkin's lymphoma (HL, n = 20, 68 malignant lesions, three benign lesions) or
      non-Hodgkin's lymphoma (NHL, n = 26, 46 malignant lesions, one benign lesion)
      were studied with positron emission tomography (PET) and fluorine-18 deoxyglucose
      (FDG). Oxygen-15 labelled water was used (n = 14, 25 lesions) in addition to FDG
      in order to obtain information on the tissue perfusion. Long-term follow-up
      studies with PET and FDG were performed in nine patients up to 511 days after the
      initiation of second-line therapy. Fourteen patients underwent single-photon
      emission tomography (SPET) with technetium-99m sestamibi immediately prior to the
      first PET examination. PET with FDG displays a high sensitivity for the detection
      of viable tumour tissue, all the malignant lesions being correctly classified in
      this study. The possible limitations are inflammatory processes, which may
      obscure tumour detection due to increased FDG uptake, and malignant lesions with
      low FDG uptake due to reduced perfusion. Difficulties exist in the prognosis of
      long-term response, since the change in FDG uptake may be variable. Long-term
      therapy outcome was correlated with the slope values obtained from the
      standardized integral uptake (SIU) data, which provides a new approach for the
      evaluation of PET follow-up studies. 99mTc-sestamibi, which should reflect the
      multidrug resistance, was evaluated with respect to therapy outcome. A high
      uptake of 99mTc-sestamibi was observed in patients with stable disease or better.
      The data support the hypothesis that sestamibi may reflect multidrug
      resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7641754
TI  - Technetium-99m antimyosin antibody (3-48) myocardial imaging: human
      biodistribution, safety and clinical results in detection of acute myocardial
      infarction.
AB  - Technetium-99m antimyosin (99mTc-AM) antibody imaging may have significant
      advantages over indium-111 antimyosin in clinical practice. The purpose of this
      study was to determine the human biodistribution, the safety profile and the
      sensitivity of 99mTc-AM (3-48) imaging in the detection of both Q-wave and non-Q
      wave myocardial infarction (MI). Biodistribution and safety parameters were
      mainly determined in 12 normal healthy volunteers while 40 patients with proven
      MI (22 Q-wave, 18 non-Q-wave) were injected with 99mTc-AM (20-25 mCi) between 5 h
      and 7 days after the onset of acute chest pain. Three standard planar views were
      performed at 6 h and at 24 h post injection. Both sets of images were completed
      in 33 patients while two patients were imaged only at 6 h, three patients only at
      18 h and one at 18 and 24 h. One patient was not imaged. Vital signs and ECG were
      recorded and blood samples for haematology, biochemistry and human antimurine
      antibodies (HAMA) and urinalysis were obtained in all volunteers and patients. No
      serious adverse reactions or side-effects attributable to 99mTc-AM have been
      reported. No volunteers or patients developed allergic reactions or significant
      increases in HAMA titres. Reading of 99mTc-AM imaging was performed by two
      blinded experienced observers. The sensitivity of 99mTc-AM in the detection of MI
      was 100% (21/21) for Q-wave and 83.3% (15/18) for non-Q-wave infarctions. The
      overall sensitivity was 92.3% (36/39). The three false-negative cases were
      inferoposterior MI. A certain degree of uptake focalization was seen in 26 out of
      35 (74.2%) at 6 h. At 24 h, two patients (5.8%) did not show 99mTc-AM uptake
      while 22 (64.7%) showed intense focal uptake, seven (20.6%) moderate uptake and 3
      (8.9%) slight uptake. It is concluded that 99mTc-AM (3-48) imaging is safe and
      shows high sensitivity in the detection of both Q-wave and non-Q-wave MI even
      with early imaging (6 h post injection). These promising results warrant further
      clinical investigation.

PMID- 7641753
TI  - Sympathetic re-innervation after heart transplantation: dual-isotope
      neurotransmitter scintigraphy, norepinephrine content and histological
      examination.
AB  - Cardiac transplantation entails surgical disruption of the sympathetic nerve
      fibres from their somata, resulting in sympathetic denervation. In order to
      investigate the occurrence of sympathetic re-innervation, neurotransmitter
      scintigraphy using the norepinephrine analogue iodine-123 metaiodobenzylguanidine
      (MIBG) was performed in 15 patients 2-69 months after transplantation. In
      addition, norepinephrine content and immunohistochemical reactions of antibodies
      to Schwann cell-associated S100 protein, to neuron-specific enolase (NSE) and to
      norepinephrine were examined in 34 endomyocardial biopsies of 29 patients 1-88
      months after transplantation. Anterobasal 123I-MIBG uptake indicating partial
      sympathetic re-innervation could be shown in 40% of the scintigraphically
      investigated patients 37-69 months after transplantation. In immunohistochemical
      studies 83% of the patients investigated 1-72 months after transplantation showed
      nerve fibres in their biopsies but not positive reaction to norepinephrine.
      Significant norepinephrine content indicating re-innervation could not be
      detected in any biopsy. It was concluded that in spite of the lack of
      norepinephrine content there seemed to be immunohistological and scintigraphic
      evidence of sympathetic re-innervation. An explanation for this contradictory
      finding may be the reduced or missing norepinephrine storage ability compared to
      the restored uptake ability of regenerated sympathetic nerve fibres.

PMID- 7641755
TI  - Simultaneous dual-isotope technetium-99m/thallium-201 cardiac SPET imaging using
      a projection-dependent spilldown correction factor.
AB  - A spilldown correction method is proposed for the thallium-201 window image in
      simultaneous dual-isotope technetium-99m/thallium-201 single-photon emission
      tomographic (SPET) imaging based on a single acquisition into three energy
      windows. In this method, images are simultaneously acquired in two standard
      energy windows over the 99mTc and 201Tl photopeak regions and a third spilldown
      window adjacent to the 201Tl window. Using a Monte Carlo simulation of SPET, the
      fractional amount of 99mTc and 201Tl spilldown in the 201Tl window with respect
      to the total counts from the spilldown window, k12, was calculated for simulated
      images of point sources at varying depths within a water-filled elliptical tub
      phantom. When applied to experimental acquisitions, k12, multiplied by the total
      counts from the spilldown window, is then subtracted from the 201Tl window image
      to produce the corrected image. However, for successful applications in SPET, k12
      must be determined on a projection-by-projection basis since k12 is depth
      dependent. Thus, a regression relation was obtained between k12 and the total
      count ratio of the spilldown to 99mTc windows, k23. The spilldown correction
      method was applied to 201Tl photopeak images of an extended source distribution
      in uniform and nonuniform attenuating media with dual-isotope 99mTc/201Tl and
      single-isotope 201Tl. A marked improvement in image contrast was observed between
      the corrected and uncorrected 201Tl window images. The average count ratio of
      uncorrected dual-isotope 201Tl/single-isotope 201Tl was 3.08 for uniform and 2.99
      for non-uniform attenuating media.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7641756
TI  - Technegas and Pertechnegas particle size distribution.
AB  - Technegas and Pertechnegas are radioactive aerosols produced in a commercial
      generator and used for lung scintigraphy. The aerosols are produced by first
      evaporating to dryness standard technetium-99m generator eluate (99mTcO4 in
      normal saline) in a graphite crucible (the simmer stage) and then heating this to
      2500 degrees C (the "burn" stage). The aim of this work was to measure the
      particle size distributions of these agents and relate this to regional lung
      deposition. Factors that may vary during production of the aerosol in routine use
      were investigated to determine whether they influenced the particle size.
      Activity size distributions were measured using a serial wire-screen diffusion
      battery. The Technegas size distribution was approximately log-normal with an
      activity median diameter of 158 nm and a geometric standard deviation of 1.5. The
      results for Pertechnegas were similar. The median size increased with the number
      of simmers and with the time from generation. The increase in size with the
      number of simmers is thought to be due to the increased salt content in the
      crucible prior to the "burn". The predicted lung deposition is 37% in the
      alveolar region and 5% in the bronchial region. Significant changes in deposition
      are not predicted over the range of particle sizes measured.

PMID- 7641757
TI  - Quality assurance and harmonisation of nuclear medicine investigations in Europe.
AB  - A survey of all member societies of the European Association of Nuclear Medicine
      has shown that a satisfactory degree of harmonisation exists for the quality
      assurance of the preparation and handling of radiopharmaceuticals and the
      performance of nuclear medicine instrumentation. However, variations were found
      in acquisition protocols, data analysis and the interpretation and presentation
      of clinical results. Harmonisation of these areas of a nuclear medicine
      investigation would help ensure the overall quality. A European initiative is
      proposed to collect and collate procedures in these areas in order to produce a
      reference framework of good practice for the acquisition, analysis and
      interpretation of nuclear medicine investigations. This would involve
      collaboration between national societies and exchange of information with and
      support from European organisations, taking into account relevant international
      activities. The reference framework should be compatible with quality management
      guidelines.

PMID- 7641759
TI  - The nuclear medicine physician and clinicians in the 1990's.

PMID- 7641758
TI  - Hormesis: are low doses of ionizing radiation harmful or beneficial?
AB  - A review is provided of the literature on radiation hormesis, hormesis being any
      physiological effect that occurs at low doses and which cannot be anticipated by
      extrapolating from toxic effects noted at high doses. Epidemiological studies
      suggesting beneficial effects are considered, and experimental evidence for the
      existence of hormesis is then appraised. In the latter context, there are
      possible low-dose effects at the molecular level, at the cellular level and on
      the organism as a whole. It is concluded that while it is difficult to analyse
      the effects of low-dose radiation with statistical significance, the concept does
      permit the reconsideration of the validity of currently accepted notions.

PMID- 7641760
TI  - Environmental aspects in pediatrics. New item in the European Journal of
      Pediatrics.

PMID- 7641761
TI  - The pioneers of pediatric medicine. John F. Enders (1897-1985).

PMID- 7641762
TI  - Late effects of anthracycline therapy in childhood in relation to the function of
      the heart at rest and under physical stress.
AB  - To evaluate the long-term effects of anthracyclines on the myocardium of the
      young child we examined 34 patients who had been treated with anthracyclines in
      childhood. In addition to anthracycline, the patients were treated with other
      potentially cardiotoxic substances within the framework of different protocols.
      The mean cumulative anthracycline dose was 128.6 mg/m2, the average age at onset
      of chemotherapy 4.2 years, and the time interval after discontinuation of
      treatment 9.0 years. The cardiological examination consisted of a physical
      examination, electrocardiography and echocardiography, including Doppler and bio
      impedance cardiography. The patients were studied at rest and after physical
      exercise with a cycle ergometer test in a supine position. The results of the
      physical examination, the electrocardiogram at rest and the 24 h Holter
      monitoring were normal. The left ventricular enddiastolic diameter, shortening
      fraction, velocity of fibre shortening (VCF), the diastolic flow profile at the
      mitral valve level and the cardiac stroke volume at rest were also normal.
      However, the shortening fraction (SF) was below the margin of 2 standard
      deviations in two patients and the VCF in three patients. There was a significant
      reduction in septal thickness, (-1.4 SD, P < 0.0004), in the width of left
      ventricular posterior wall (-1.5 SD, P > 0.0002) and in the left ventricular
      myocardial mass (-0.76 SD, P = 0.0042). Physical working capacity was normal.
      Immediately after physical stress the expected rise of SF and VCF did not occur
      and the SF fell below the values at rest. In comparison to a healthy control
      group the SF and the VCF were markedly decreased (P > 0.0001).(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7641763
TI  - Follow up of growth and steroids in premature adrenarche.
AB  - In a follow up study of 34 patients with premature adrenarche we examined serum
      adrenal androgen levels and growth. The majority (28/34) showed an upward bend in
      the growth curve which, at the mean age of 2.3 years, preceded other signs of
      adrenarche on average by 3.8 years. Pubertal growth spurt was missing or reduced
      in 50% of the patients (8/16), however, final height did not differ from that
      expected from parental heights. Adrenal androgens did not remain elevated at
      adolescence. The mean age at menarche for all the girls was 0.5 years younger
      than in the general population. CONCLUSION: Our findings imply that premature
      adrenarche may start earlier than previously recognized. Compared to ordinary
      growth these children seem to use a greater part of their potential for adult
      height already at that early age.

PMID- 7641764
TI  - Glycaemic responses to commonly ingested breakfasts in children with insulin
      dependent diabetes mellitus.
AB  - The glycaemic response to commonly ingested breakfast with different glycaemic
      index (cornflakes, white bread, dark rye bread and muesli) was investigated in 14
      children with insulin-dependent diabetes mellitus. The blood glucose response
      after cornflakes was significantly higher than after the other breakfasts,
      whereas the areas under the blood glucose curve were not statistically different.
      We observed no difference in blood glucose rise between the other breakfast
      types. CONCLUSION: Postprandial blood glucose measurements after meals with high
      glycaemic index may be useful in order to minimize the postprandial rise in blood
      glucose.

PMID- 7641765
TI  - Reduced pancreatic insulin release and reduced peripheral insulin sensitivity
      contribute to hyperglycaemia in cystic fibrosis.
AB  - Traditional opinion holds that patients with cystic fibrosis (CF) develop
      impaired glucose tolerance or diabetes due to insulinopenia caused by fibrosis of
      the pancreas. However, studies on the dynamics of insulin secretion and
      peripheral insulin action have yielded conflicting results. We studied 18
      patients with CF (9 male, 9 female, age 15-29 years) and 17 healthy control
      subjects (8 male, 9 female, 20-32 years). Oral glucose tolerance tests and
      combined i.v.-glucose-tolbutamide-tests were performed on separate days in
      fasting subjects. Bergman's "Minimal Model" was used to quantitate both
      peripheral insulin sensitivity (SI) and insulin-independent glucose disposal
      (glucose effectiveness; SG). Based on National Diabetes Data Group criteria, 4
      patients were classified as diabetic (22%; CF-DM), 3 patients (17%) had impaired
      glucose tolerance (CF-IGT) while glucose metabolism was normal in 11 patients
      (61%; CF-NGT). Irrespective of the degree of glucose tolerance, the insulin
      response to oral glucose was not reduced but delayed, up to 60 min in the CF
      IGT/DM group. First-phase insulin release (0-10 min) after i.v.-glucose was
      significantly lower in CF patients (29% of healthy controls; P < 0.0001), with no
      difference between the CF-NGT and CF-IGT/DM groups. Insulin release following
      tolbutamide injection was only marginally reduced in CF patients (64% of
      controls). In contrast, SI was significantly reduced in the subgroup of CF
      patients with abnormal glucose metabolism (CF-IGT/DM: 0.97 +/- 0.16 x 10(-4)
      l/min/pmol; control group: 1.95 +/- 0.25; P < 0.05).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7641766
TI  - Fructose breath hydrogen tests in infants with chronic non-specific diarrhoea.
AB  - Clear fluids high in fructose (e.g., apple juice) have been incriminated for
      symptoms of chronic non-specific diarrhoea (CNSD), in particular in children 1-4
      years of age. H2 breath tests were performed, after ingestion of fructose (1
      g/kg), in 15 patients referred with CNSD and 35 controls. All 15 CNSD children
      (100%) had breath peak H2 of > or = 20 ppm versus 49% of the 35 controls (P =
      0.0005). Median peak H2 in CNSD (90 ppm, range 31-136) was significantly higher
      than in controls (20 ppm, range 1-139) (P < 0.001). Orocoecal transit time in
      children with positive tests was similar in both groups. Similarly, median H2
      increases during the test period had the same distribution. We demonstrated
      fructose malabsorption in CNSD, but found a great overlap with the control group.
      Our results strongly discourage the use of fructose breath H2 tests in children
      suspected of CNSD. A positive test has no diagnostic value and a negative test
      has no clinical implications. CONCLUSION: For clinical practice, we suggest a
      dietary history and a trial of appropriate measures in infants with chronic
      nonspecific diarrhoea, instead of performing the fructose H2 breath test.

PMID- 7641767
TI  - Chronic consumption coagulopathy due to an occult splenic haemangioma: Kasabach
      Merritt syndrome.
AB  - We report an 11-year-old girl with a 2-year history of bruising associated with
      thrombocytopenia and dysfibrinogenaemia. On admission she presented with a large
      subcutaneous haematoma and splenomegaly and was severely anaemic. Laboratory
      investigations revealed signs of consumption coagulopathy. Radiological
      examination showed splenic, retroperitoneal and intra-ossal haemangiomas. After
      splenectomy, platelet count and coagulation parameters returned to normal.
      CONCLUSION: Contrary to widely held views, occult visceral haemangioma can lead
      to Kasabach-Merritt syndrome beyond infancy and is not necessarily associated
      with visible cutaneous haemangioma. It should be included in the differential
      diagnosis of chronic thrombocytopenia at any age. Early determination of
      fibrinogen degradation product levels is advised in order to detect an underlying
      chronic consumption coagulopathy prompted by an extensive search for multifocal
      haemangioma.

PMID- 7641768
TI  - Acute promyelocytic leukaemia with hypogranular bone marrow blasts in a 16-year
      old girl: diagnostic value of different genetic methods.
AB  - We report a 16-year-old girl who presented with anaemia, thrombocytopenia,
      leukocytosis and disseminated intravascular coagulation. Bone marrow analysis
      showed promyelocyte-like myeloblasts with rare Auer rods and very few granula.
      CD2 antigen was not expressed in bone marrow blasts. Karyotype analysis revealed
      a complex pattern of chromosomal aberrations without the promyelocytic leukaemia
      (PML) specific translocation t(15;17) (q22;q21). Southern blot analysis revealed
      a rearrangement of the retinoic acid receptor alpha (RAR alpha) locus. Reverse
      transcribed polymerase chain reaction assay confirmed the initial diagnosis of
      PML by amplification of the PML-specific PML/RAR alpha fusion transcript.
      CONCLUSION: This case report confirms that a characteristic translocation
      t(15;17) is not always detectable in PML blasts by karyotype analysis despite
      presence of specific PML/RAR alpha-transcripts. Together with careful
      morphological analysis of bone marrow blasts this assay apparently is the most
      specific and sensitive method to confirm the diagnosis.

PMID- 7641769
TI  - Evaluation of the polymerase chain reaction for the detection of Borrelia
      burgdorferi in cerebrospinal fluid of children with acute peripheral facial
      palsy.
AB  - Neuroborreliosis occasionally represents a diagnostic problem, especially in the
      early stage of the infection. The polymerase chain reaction (PCR) offers an
      attractive alternative to antibody testing. The aim of our study was to
      investigate the diagnostic potential of PCR in comparison to antibody tests in
      CSF of children with facial palsy. In contrast to other manifestations of
      neuroborreliosis, facial palsy is a well-defined clinical entity in which CSF
      findings allow an early distinction according to aetiology. The study included 17
      children with neuroborreliosis, defined by the detection of specific IgM
      antibodies in CSF, and 20 children with facial palsy of unknown cause. Primers
      used for the nested PCR were generated from conserved sequences of the OspA-gene.
      Most of the cases in both subgroups have been examined within a few days after
      the onset of the paresis. Only in 2 out of 17 cases with neuroborreliosis could
      specific DNA be amplified. The PCR gave negative results in all cases of the
      control group. CONCLUSION: The IgM capture ELISA is superior to PCR to support
      the clinical diagnosis of neuroborreliosis.

PMID- 7641770
TI  - Acute transverse myelitis caused by ECHO virus type 18 infection.
AB  - A 14-year-old boy developed acute quadriplegia, associated with sensory
      impairment and bowel and urinary dysfunction. MRI of the cervical cord showed
      diffuse increased signal intensity on T2-weighted images with gadolinium
      diethylenetriamine penta-acetic acid enhancement. Based on the clinical
      presentation and MRI findings, the diagnosis of acute transverse myelitis was
      made. Enterovirus RNA was amplified from CSF by the reverse transcriptase
      polymerase chain reaction. Serum neutralizing antibody to ECHO virus type 18 rose
      from 1/4 on admission to 1/16 2 months later. CONCLUSION: This is the first
      reported case of acute transverse myelitis caused by ECHO virus type 18
      infection.

PMID- 7641771
TI  - Corynebacterium diphtheriae osteomyelitis in an immunocompetent child: a case
      report.
AB  - Septic osteomyelitis of the hip in a previously healthy child is described. A
      weakly toxigenic Corynebacterium diphtheriae strain was isolated from the bone
      aspirate. The results of the treatment were rapidly satisfactory, after surgical
      drainage and antibiotic therapy with pristinamycin. CONCLUSION: This case report
      shows that C. diphtheriae has not disappeared in the developed world and can be
      responsible of systemic infections.

PMID- 7641772
TI  - Acral dysostosis dyserythropoiesis syndrome.
AB  - The term congenital dyserythropoietic anaemia (CDA) designates a group of rare
      but well defined erythrocytic disorders. Type I is defined by macrocytosis and
      megaloblastic changes of the bone marrow cells. Two unrelated children with CDA
      are described with associated defects: absence of nails and short or absent
      phalanges, polysyndactyly of the fourth metacarpal. One of them had also areas of
      depigmentation. CONCLUSION: The association of congenital dyserythropoietic
      anaemia with morphological defects of hands and feet is suggested to constitute a
      new syndrome caused by a single morphogenetic gene.

PMID- 7641773
TI  - Lens sorbitol dehydrogenase deficiency in a patient with congenital cataract.
AB  - Lens sorbitol dehydrogenase activity was assayed in patients with congenital
      cataracts, senile cataracts, without cataracts and in one fetal lens. In patients
      with congenital cataracts we did not observe any abnormality of galactose and
      sorbitol metabolising enzymes in erythrocytes. In one of these patients with
      inexplicable congenital cataracts lens sorbitol dehydrogenase deficiency was
      found. CONCLUSION: Determination of galactose metabolising enzymes, sorbitol
      dehydrogenase and polyols in lenses may help in understanding the mechanism of
      formation of inexplicable congenital cataracts.

PMID- 7641774
TI  - Lung volume and pulmonary blood flow measurements following exogenous surfactant.
AB  - Lung function in eight infants with clinical and radiological features of
      surfactant deficiency treated with exogenous porcine surfactant was studied
      before and at 15 min, 2h and 6h after the intratracheal administration of porcine
      surfactant. We measured alveolar-arterial oxygen tension difference, dynamic lung
      compliance, lung volume and effective pulmonary blood flow in all infants. The
      alveolar-arterial oxygen tension difference fell from a mean (SD) 43.3 (14.5) kPa
      before treatment to 8.8 (8.8) kPa at 1 h and 12.2 (6.8) kPa 6h after treatment (P
      < 0.001). There was no change in mean (SD) dynamic compliance (0.39 [0.10]
      ml/cmH2O/kg pre dose; 0.36 [0.13] ml/cmH2O/kg 6h post treatment). Accessible
      functional residual capacity and effective pulmonary blood flow were measured
      using an adaptation of the argon/freon rebreathing method and showed an increase
      in mean (SD) functional residual capacity from 7.5 (1.4) ml/kg predose to 10.8
      (3.3) ml/kg within 15 min of treatment, 11.4 (3.4) ml/kg 2h later and 12.7 (3.1)
      ml/kg 6h after treatment (P = 0.009). Mean (SD) effective pulmonary blood flow
      values did not differ significantly, changing from 78.2 (20.9) ml/kg per min
      predose to 88.7 (24.1) ml/kg per min 15 min post dose, 87.6 (21.7) ml/kg per min
      2h post dose and 90.0 (22.7) ml/kg per min 6h post dose (P = 0.711). CONCLUSION:
      The improvement in oxygenation after surfactant treatment is associated with an
      increase in lung volume but is not related to an improvement in dynamic lung
      compliance or effective pulmonary blood flow. The change in lung volume is
      detectable within 15 min of administration of the surfactant.

PMID- 7641775
TI  - Adult stature and anthropomorphic measurements of patients with myelomeningocele.
AB  - Children with myelomeningocele are extremely short, yet little data exists on
      adult stature and anthropomorphic measurements. We measured the recumbent length,
      weight, arm length, sitting height and calculated body mass index of 54 adults
      with myelomeningocele. Mid parental height was also calculated. Measurements were
      compared with normative data. Patient charts were reviewed for history of
      hydrocephalus. The 27 males and 27 females had a mean age of 24.8 +/- 5.7 years.
      The mean length for adult females was 141.9 +/- 12 cm and was 152.1 +/- 13 cm for
      males. Patients with thoracic level of lesions were shorter than those with
      lumbar level who were, in turn, shorter than those with sacral levels. Recumbent
      length, sitting height, arm length and arm span were significantly smaller than
      expected values. Recumbent length was smaller than mid parental height. Those
      with ventriculoperitoneal shunts, required for hydrocephalus, were shorter than
      these without a shunt. CONCLUSION: Adults with myelomeningocele have significant
      short stature. Arm span is not an interchangeable measure with length for
      patients with myelomeningocele. Multiple factors are likely to be responsible for
      the observed short stature.

PMID- 7641776
TI  - Serum sodium levels and probability of recurrent febrile convulsions.
AB  - In a prospective study of 69 children with febrile convulsions, serum sodium
      levels were often lower than normal (52% had levels < 135 mmol/l). The mean level
      (134.4 +/- 0.4 mmol/l) was significantly lower as compared to a group of children
      without fever (140.6 +/- 0.4 mmol/l, n = 23) and as compared to a group with
      fever but without convulsions (137.6 +/- 0.6 mmol/l, n = 31). The probability of
      a repeat convulsion within the same febrile period appeared to be significantly
      related to the serum sodium level. CONCLUSION: Measurement of the serum sodium is
      a valuable investigation in the child with a febrile convulsion. The lower the
      serum sodium level, the higher the probability of a repeat convulsion. This
      knowledge may be of practical value in deciding whether to admit the child or
      allow it to return home and in advising parents or carers of the risk of a repeat
      convulsion.

PMID- 7641777
TI  - Migraine of gastrointestinal origin.
AB  - A consecutive series of 31 children (median age 12 years) suffering from migraine
      with (n = 21) or without (n = 10) aura underwent endoscopic oesophageal, gastric
      and duodenal biopsy in order to determine whether the complaints were of gastro
      intestinal origin. Of these 31 children, 13 (41.9%) showed oesophagitis, 16
      (51.6%) gastritis of corpus, 12 (38.7%) antral gastritis and 27 (87.1%)
      duodenitis. Thus, 29 of the 31 children studied had an underlying inflammatory
      lesion explaining their complaints. Helicobacter pylori colonization was found in
      7 of the children: one had H. pylori associated antral and corporal gastritis and
      6 H. pylori associated antral gastritis only. Gastritis of corpus without H.
      pylori was present in all these 6 children. Our data do not support that H.
      pylori is a primary pathogen of inflammatory changes seen in children studied,
      neither do they establish an association between H. pylori, antral gastritis and
      migraine. However, our data strongly suggest that there is a gastro-intestinal
      origin of these patients' complaints. CONCLUSION: Our findings provide further
      evidence that recurrent abdominal pain is an early expression of migraine and
      strongly support a causal link between recurrent abdominal pain and migraine.

PMID- 7641778
TI  - Reversible hepatic dysfunction in association with cyclophosphamide therapy.
AB  - A 5.5-year-old child with nephrotic syndrome was treated with cyclophosphamide.
      After 9 weeks of therapy she developed jaundice and abnormal liver function
      tests. No infective aetiology was found and the abnormal liver function tests
      resolved within 5 weeks of discontinuing cyclophosphamide. Cyclophosphamide has
      rarely been reported to cause liver dysfunction, but not in children treated for
      nephrotic syndrome, and paediatricians should therefore be aware of its potential
      for inducing reversible hepatic dysfunction.

PMID- 7641779
TI  - Two cases of pulmonary tuberculosis presenting with unilateral pulmonary
      hyperinflation in infancy.
AB  - Two infants with recurrent obstructive symptoms attracted attention because of
      massive radiologically detected unilateral pulmonary hyperinflation. Further
      diagnostic procedures including bronchoscopy, revealed a pulmonary tuberculosis
      with lymph nodes encroaching on the bronchi. Steady improvement of clinical
      symptoms and hyperinflation was noted under combined antituberculotic therapy
      including systemic steroids. CONCLUSION: Our two cases demonstrate that the
      differential diagnosis of unilateral pulmonary hyperinflation and wheezing in
      infancy should consider valvular stenosis by encroaching lymph node due to
      pulmonary tuberculosis.

PMID- 7641780
TI  - Gaucher disease associated with congenital ichthyosis in the neonate.

PMID- 7641781
TI  - Leukaemia in children with growth hormone deficiency not treated with growth
      hormone.

PMID- 7641782
TI  - Lymphocyte subpopulations in newborns.

PMID- 7641783
TI  - Sudden infant death and multiple acyl-CoA dehydrogenation disorders.

PMID- 7641784
TI  - Properties of incompletely immortalized cell lines generated from a line
      established from temperature-sensitive SV40 T-antigen gene transgenic mice.
AB  - Kidney tubule cell line (TKC2) established from temperature-sensitive (ts) SV40 T
      antigen gene transgenic mice exhibited cell death by apoptosis at nonpermissive
      temperature (39 degrees C). To learn how immortalization occurs, we generated T
      antigen-independent immortalized cells (resistant clones) by culturing TKC2 cells
      at 39 degrees C. These independently isolated resistant clones exhibited ts
      properties in T-antigen and contained only wild-type p53. They grew similarly at
      39 degrees and at 33 degrees C, but cell death was induced soon after they
      reached confluency at 39 degrees C. However, cell death was equally prevented by
      transfecting the bcl-2 gene. While TGF-beta showed no growth-suppressive effect
      in the sensitive and resistant clones at 33 degrees C, it induced significantly
      earlier cell death in the resistant clones at 39 degrees C. Thus, the resistant
      clones may be incompletely immortalized cell lines which induce cell death in
      response to the growth-suppressive effects of contact inhibition.

PMID- 7641785
TI  - Localization of transforming growth factor-beta type I and type II receptors in
      mouse development.
AB  - We have investigated the localization pattern of the transforming growth factor
      beta (TGF-beta) receptors type I (T beta R-I) and type II (T beta R-II) during
      mouse organogenesis by immunohistochemical analysis. Staining of both receptors
      was found in many developing organs, e.g., bone, teeth, Meckel's cartilage, and
      neural tissues, where the expression of their ligands has been previously
      reported. During the investigated stages, expression of T beta R-I was more
      ubiquitous than that of T beta R-II. T beta R-II preferentially localized in the
      undifferentiated mesenchymal cells which subsequently differentiated into bone.
      There was no staining of T beta R-II in the central nervous system, while intense
      T beta R-I staining was found specifically in nervous tissues. Expression of T
      beta R-I and T beta R-II was mostly coincident with that of their ligands,
      suggesting that TGF-beta s act as multiple mediators during organogenesis. In
      addition, colocalization of both receptors in the epithelia of the tooth bud and
      submandibular gland, which were actively invaginating into the mesenchyme, leads
      us to speculate that both receptors may be necessary for dynamic epithelial
      morphogenesis.

PMID- 7641786
TI  - Expression of heat shock protein 90 (hsp90) in neural and nonneural tissues of
      the control and hyperthermic rabbit.
AB  - Tissue-specific differences were apparent in the constitutive level of hsp90 in
      various body tissues of the unstressed rabbit. Western blotting with monoclonal
      antibody 29A revealed very low levels in muscle and highest levels in neural
      regions (cerebellum, cerebral hemispheres, and retina) and in testes and thymus.
      Intermediate levels were apparent in other tissues such as liver, kidney, heart,
      and small intestine. Following hyperthermia, induction of hsp90 was not detected
      with 1-D Western blotting in tissues which demonstrated high constitutive levels;
      however, elevations were noted in tissues which showed lower constitutive amounts
      of the protein, such as kidney, heart, and muscle. Immunocytochemical studies
      revealed that hsp90 is preferentially localized to neuronal cell populations in
      the rabbit brain and that this pattern does not alter following hyperthermic
      conditions which result in glial induction of hsp70. In kidney, where
      constitutive levels of hsp90 are lower than in brain, an induction of hsp90 was
      noted in renal tubules following hyperthermia.

PMID- 7641787
TI  - Sensitive and rapid detection of beta-galactosidase expression in intact cells by
      microinjection of fluorescent substrate.
AB  - Bacterial beta-galactosidase, coded by lacZ, is a widely used reporter for
      studies of transcriptional activity of eukaryotic promoters at the single cell
      level. Unfortunately, current detection methods, like X-gal cytochemistry, are
      slow, have suboptimal sensitivity, and are incompatible with cell survival. By a
      novel approach based on microinjection into cells of the fluorogenic substrate 5
      chloromethylfluorescein di-beta-D-galactopyranoside lacZ gene expression was
      detected without affecting cell viability or proliferative capacity. The method
      was far more sensitive than the conventional X-gal cytochemistry in all cell
      systems tested (primary hepatocytes, fibroblasts, and glioma cells). Results were
      obtained within seconds to minutes after injection, and cells remained
      fluorescent for hours.

PMID- 7641788
TI  - Overexpression of annexin V in cystic fibrosis epithelial cells from fetal
      trachea.
AB  - In this report, we investigated the expression of annexins I, II, V, and VI by
      Northern and Western blot analysis in four cell lines isolated from human fetal
      tracheae. Two cell lines were obtained from normal fetuses and the two others
      from fetuses with cystic fibrosis (CF). One CF fetus was heterozygous for the
      S549N and N1303K substitutions, whereas the other was homozygous for the delta
      F508 deletion. We found that the four annexins are always coexpressed. The
      expression of annexins I, II, and VI was the same in the four cell lines. In
      contrast, that of annexin V was significantly higher in CF than in normal cells.
      These observations demonstrate that annexins I, II, V, and VI are independently
      regulated in tracheal epithelial cell lines. Moreover, they suggest that the
      overexpressed annexin V, a Ca2+ channel, might profoundly modify Ca2+ transport
      across the membranes of CF cells.

PMID- 7641789
TI  - Biphasic pattern of gelsolin expression and variations in gelsolin-actin
      interactions during myogenesis.
AB  - During myogenesis in vitro, the amount of gelsolin in myogenic cells increased by
      a factor of approximately 3 from about 200 ng to a maximum of 750 ng per
      milligram of total protein. Gelsolin increased steadily from the myoblast state
      to terminally differentiated myotubes containing abundant cross-striated
      myofibrils. At the same time, the amount of total actin varied by only about 30%,
      the molar ratio of gelsolin:actin increased from 1:500 to approximately 1:150.
      This modulation of gelsolin expression was observed both in avian and mammalian
      myocultures. Once the state of terminal differentiation in myocultures was
      attained, the amount of gelsolin decreased again. On the other hand, gelsolin
      decreased continuously in the postnatal mouse muscle by a factor of approximately
      5 between Day 1 and Day 12 after birth. When myogenic cells from various stages
      of differentiation were extracted with Triton X-100, the majority of gelsolin was
      soluble, whereas a minor fraction was tightly associated with the cytoskeleton.
      The actual amount of insoluble gelsolin depended on both the Ca2+ concentration
      during extraction and the degree of differentiation. Whereas at [Ca2+] > 10(-5) M
      about one-third of the total gelsolin was associated with the cytoskeleton at all
      stages of differentiation, the amount of insoluble gelsolin after Triton
      extraction in the presence of EGTA increased from 3 to 17% during
      differentiation. The amount of soluble actin decreased from 40 to 25% during the
      same period, independent of the Ca2+ concentration. We calculated that the amount
      of gelsolin associated with the cytoskeletal or myofibrillar system is
      approximately 20-fold higher in differentiated myotubes than in early myotubes,
      indicating a functional role of gelsolin for myofibrillar assembly.

PMID- 7641790
TI  - Identification of vinculin as a pericentriolar component in mammalian cells.
AB  - Previous studies have shown that centrosome position and structure can be
      influenced by actin filaments, that centrosomes can influence actin organization,
      and that an actin homologue is associated with centrosomes. Such observations
      suggest the existence of connections between centrosomes and actin networks. In
      keeping with such observations, we show that the pericentriolar material, a main
      component of centrosomes, contains vinculin, a well-known component of cell
      adhesion plaques and of adherens cell junctions. We find that in various cell
      types, centrosomes are specifically stained by five different anti-vinculin
      antibodies. In adherent cell lines, these antibodies also stained adhesion
      plaques, but in thymocytes, a cell type devoid of adhesive structures, such
      antibodies stained only centrosomes. Isolated centrosomes also reacted with the
      anti-vinculin antibodies and immunoelectron microscopy showed apparent
      localization of vinculin in the pericentriolar material. Immunoblot analysis
      confirmed the presence of vinculin in purified centrosomal protein preparations.
      In such protein fractions, anti-vinculin antibodies reacted with a single
      polypeptide with an apparent molecular weight similar to that of vinculin.
      Stepwise solubilization of centrosomal structures using urea showed that high
      urea concentrations were required to solubilize centrosomal vinculin, suggesting
      tight association of vinculin with the pericentriolar material. The
      identification of vinculin as a component of centrosomes provides a possible
      molecular basis for interaction between F-actin and centrosomes.

PMID- 7641791
TI  - Molecular nature of calicin, a major basic protein of the mammalian sperm head
      cytoskeleton.
AB  - In the mammalian sperm head the nucleus is tightly associated, in many species in
      its posterior part, with a large and dense nonfilamentous cytoskeletal structure,
      the calyx, whose major proteins are basic, representing a novel category of
      cytoskeletal element. Using specific antibodies, biochemical methods, and cDNA
      cloning we have characterized one of these calyx proteins, previously termed
      calicin, in bull and man. The polypeptide of 588 amino acids (Mr of 66,889; IEP
      8.1) is very similar in the two species and is encoded by a approximately 2.2-kb
      mRNA that has been detected only in testis but not in any other tissue or cell
      culture examined. Sequence analysis has revealed that calicin is homologous to
      the kelch protein of the ring canal structure of Drosophila ovaries. In
      particular, it contains three consecutive repeating units of 48 amino acids each
      which are homologous to the so-called "beta-strand folds" occurring in proteins
      of the kelch family, including the actin cross-linking protein scruin of Limulus
      sperm and a series of other eukaryotic, bacterial, and viral proteins. Moreover,
      the amino terminal domain of calicin contains a region of about 100 amino acids
      homologous to an extended motif shared by the kelch protein as well as various
      zinc finger and poxvirus proteins. The possible role of calicin as a morphogenic
      cytoskeletal element in spermiogenic differentiation is discussed, also in
      relation to the demonstrated absence or altered arrangement of calicin in
      frequent forms of human teratozoospermia such as "round-headed" or other
      "postacrosomal sheath defect" sperm malformations.

PMID- 7641792
TI  - Mouse oocyte maturation: meiotic checkpoints.
AB  - Mouse oocytes at different stages of maturation were fused together and the
      ensuing cell cycle events were analyzed with the objective of identifying
      checkpoints in meiosis. Fusion of maturing oocytes just undergoing germinal
      vesicle breakdown (GVBD) induces PCC (premature chromosome condensation) but no
      spindle formation in immature (GV) partner oocytes. On the other hand, fusion of
      metaphase I (MI) oocytes containing spindles to GV oocytes induces both PCC and
      spindle formation in the immature partner. Thus, while molecules required for
      condensation are present throughout metaphase, those involved in spindle
      formation are absent in early M-phase. Oocytes cultured for 6 h--early metaphase
      I (i.e., approximately 2 h before the onset of anaphase I)--and then fused to
      anaphase-telophase I (A-TI) fusion partners block meiotic progression in the more
      advanced oocytes and induce chromatin dispersal on the spindle. By contrast,
      oocytes cultured for 8 h (late MI) before fusion to A-TI partners are driven into
      anaphase by signals from the more advanced oocytes and thereafter advance in
      synchrony to telophase I. When early (10 h) or late (12 h) metaphase II oocytes
      were fused to A-TI partners the signals generated from early MII oocytes block
      the anaphase to telophase I transition and induce a dispersal of A-TI chromosomes
      along the spindle. On the other hand, late MII oocytes respond to A-TI signals by
      exiting from the MII block and undergoing the A-TII transition. Moreover, the
      oocytes in late MI are not arrested in this stage and progress without any delay
      through A-TI to MII when fused to metaphase II partners. The signals from the
      less-developed partner force the MII oocyte through A-TII to MIII. In total,
      these studies demonstrate that the metaphase period is divided into at least
      three distinct phases and that a checkpoint in late metaphase controls the
      progress of meiosis in mammalian oocytes.

PMID- 7641793
TI  - Changes in shape and motility of cells transfected with parvalbumin cDNA.
AB  - Parvalbumin is thought to act as a Ca2+ buffer in skeletal muscle fibers, but its
      physiological role in brain, kidney, and testis remains unclear. We have
      transfected parvalbumin cDNA into a human ovarian adenocarcinoma cell line, which
      normally does not express this protein. The induced expression of parvalbumin
      under the control of three different promoters causes: (1) changes in the
      morphology of the cells from epitheloid to fusiform, (2) an increase in motility
      of whole cell clusters, and (3) a decrease in the mitotic rate. Transfection with
      a mutated cDNA of rat parvalbumin incapable of binding Ca2+ had no effect on
      these three parameters. Our results indicate that ectopic expression of
      parvalbumin influences not only cell division [Rasmussen and Means (1989) Mol.
      Endocrinol. 3, 588-596], but also cell shape and motility by modulating
      intracellular Ca2+ handling. This may be a basic function of parvalbumin when it
      is intrinsically expressed in differentiated nonmuscle cells.

PMID- 7641794
TI  - Elongation of confluent endothelial cells in culture: the importance of fields of
      force in the associated alterations of their cytoskeletal structure.
AB  - Studies using either animal models or in vitro flow systems have shown that the
      shape of large-vessel endothelial cells (ECs) was sensitive to the amplitude of
      the flow imposed on them. In order to better understand the morphological changes
      experienced by ECs when exposed to physical forces such as shear stress, the
      mechanical integrity of confluent bovine aortic ECs (BAECs) was anisotropically
      perturbed using the five following types of experiments: (i) slicing and partial
      scraping of BAEC monolayers; (ii) culture of BAECs on narrow strips of adhesive
      plastic; (iii) incubation of confluent BAECs with media containing low Ca2+
      concentrations; (iv) culture of ECs on top of rectangular collagen gels; and (v)
      exposure of BAECs to laminar steady shear stress. In all five experimental
      systems, BAECs exhibited an elongated morphology and aligned their major axes in
      specific directions. In addition, a preferential alignment of actin
      microfilaments, vimentin intermediate filaments, and streaks of vinculin with the
      major axes of the cells often occurred concomitantly with BAEC elongation. In all
      five systems, the elongation of ECs was analyzed in terms of a mechanical
      deformation borne by the cytoskeleton, and possibly caused by anisotropic
      distribution of the forces experienced by the cell structure. In addition, the
      strain-stress and stiffness-stress relationships characterizing the elongation of
      BAECs exposed to steady flow were qualitatively similar to those computed for the
      uniaxial deformation of a spherical geodesic. Our findings suggest that the
      cytoskeleton of ECs plays an important role in the transduction of those forces
      which cause an elongation of ECs.

PMID- 7641795
TI  - Induction of G2 arrest and gene expression by 2-aminopurine in human U937
      promonocyte-macrophage cells.
AB  - The adenine analogue, 2-aminopurine (2-AP), induces G2 arrest in the human
      promonocyte-macrophage cell line, U937. The arrest is reversible and cells enter
      mitosis to resume normal logarithmic growth upon removal of the drug. These
      physiological changes are accompanied by markedly stimulated expression of
      eukaryotic gene constructs stably integrated in the chromosomes or introduced
      into the cells by transient transfection. Induction by 2-AP has two components:
      one involves increased transcription of the introduced genes as shown by run-on
      transcription experiments. The other involves markedly increased mRNA half-life
      that affects mRNA transcribed from transiently transfected DNA but apparently
      does not affect mRNA transcribed from the same chromosomally integrated
      sequences. Together, these two components could account for the 100- to 1000-fold
      inductions observed with various transfected gene constructs reported here and
      elsewhere. Maximum induction by 2-AP is promiscuous with respect to eukaryotic
      promoter origins or sequences, but appears to require a minimum of two such
      promoter elements. Thus, G2 cell cycle arrest induced by 2-AP is also associated
      with transcriptional and post-transcriptional alterations in gene expression. The
      data also suggest that transiently transfected DNAs may enter spatial or
      biochemical compartments of the nucleus that are different from those of normal
      genes in their native locations. These differences may affect the abundance and
      fate of the transcribed mRNA and, in some circumstances, introduce serious
      discordances into studies of gene regulation.

PMID- 7641796
TI  - Activation of skeletal muscle satellite cells and the role of fibroblast growth
      factor receptors.
AB  - Specific, high-affinity binding of FGF2 was evaluated in cultured skeletal muscle
      satellite cells from young (3- to 4-week-old) and adult (9- to 12-month-old) rats
      prior to the first division in culture. Specific binding of FGF2 was detected on
      satellite cells from young rats at 18 h postplating, the earliest time examined,
      but specific binding was not detectable until 42 h on satellite cells from old
      rats. This correlates well with the delayed entry into the cell cycle exhibited
      by adult satellite cells and with the ability of satellite cells from rats of
      these ages to proliferate in response to FGF2. Patterns of tyrosine
      phosphorylation in whole cell extracts, following stimulation by FGF2, indicated
      specific FGF2 phosphorylation of proteins of 150/145, 90, 42, and 35 kDa in cells
      from both age groups. Several growth factors were evaluated for their ability to
      stimulate early entry of adult satellite cells into the cell cycle, and none of
      the following growth factors were able to activate proliferation of these cells:
      FGF2, IGF-1, IGF-2, PDGF-BB, TGF-beta 1, or TGF-beta 2. In addition, specific
      binding of FGF2 to 48-h cultures of adult satellite cells was not stimulated by
      FGF2, IGF-1, IGF-2, PDGF-BB, or TGF-beta 2, and specific binding was
      significantly decreased (P < 0.05) by FGF2 and TGF-beta 2. Specific binding was
      significantly lower in cells treated with PDGF-BB than in cells treated with
      either form of IGF but was greater than in cells treated with FGF2 or TGF-beta 2.
      The results of these experiments suggest that expression of functional FGF
      receptors on the surface of satellite cells may represent an important step in
      the activation of quiescent satellite cells.

PMID- 7641797
TI  - Phosphatidylinositol 3-kinase activity in murine erythroleukemia cells during
      DMSO-induced differentiation.
AB  - We have used murine erythroleukemia cells (MEL cells) to investigate the role of
      phosphatidylinositol 3-kinase (PI 3-kinase) in erythroid differentiation. When
      treated with dimethyl sulfoxide (DMSO), MEL cells grown on a fibronectin matrix
      become committed to erythroid differentiation asynchronously, with 90% of cells
      becoming committed by Day 3 of treatment. We found that during the first 3 days
      of DMSO treatment MEL cells showed a twofold increase in total PI 3-kinase
      activity and a fourfold increase in the highly phosphorylated PI 3-kinase
      product, PIP3. At the same time there was no change in the content of p85, the PI
      3-kinase regulatory subunit. After Day 3, PI 3-kinase activity declined, in
      parallel with a disappearance of p85 antigen from the cells. Inclusion of the PI
      3-kinase inhibitor Wortmannin in the culture medium resulted in an inhibition of
      cellular PI 3-kinase activity and a delay in DMSO-induced erythroid
      differentiation. These data suggest that PI 3-kinase may play a critical role
      during commitment of MEL cells to erythroid differentiation.

PMID- 7641798
TI  - Farnesyl acetate, a derivative of an isoprenoid of the mevalonate pathway,
      inhibits DNA replication in hamster and human cells.
AB  - Cells treated with compactin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme
      A (HMG-CoA) reductase, the enzyme which catalyzes the rate-limiting step of the
      mevalonate pathway, are arrested prior to the DNA synthesis (S) phase of the cell
      cycle. Identification of a specific pathway product or products with a role in
      DNA replication, however, has remained elusive. In this report we demonstrate
      that farnesyl acetate, a derivative of the key isoprenoid pathway intermediate
      farnesyl pyrophosphate, inhibits DNA replication in both Chinese hamster ovary
      cells and human (HeLa) cells. This effect is revealed by measurement of DNA
      content using fluorescence-activated cell sorter analysis and by measurement of
      [3H]thymidine incorporation. We show that cells treated with farnesyl acetate
      retain protein synthesis capacity as DNA replication is inhibited and remain
      intact as viewed with the vital stain propidium iodide. The inhibition of DNA
      replication by farnesyl acetate occurs in cells treated with high levels of
      compactin and in cells lacking HMG-CoA reductase. These results indicate that
      farnesyl acetate action is not dependent on metabolism through the isoprenoid
      pathway and is not the result of the loss of a metabolite required for
      replication nor the accumulation of a metabolite which is inhibitory. In
      addition, cells treated with farnesyl acetate for over 6 h are irreversibly
      blocked from progressing through S phase, a phenomenon which differs sharply from
      the results with compactin, removal of which results in synchronous progression
      through S phase. Farnesyl acetate also blocks protein prenylation in cells, to a
      degree comparable to a known farnesylation inhibitor, BZA-5B. We propose that
      farnesyl acetate is acting in a manner quite different from the metabolic block
      caused by compactin, causing a rapid and irreversible block of DNA replication.

PMID- 7641799
TI  - Beta-endorphin stimulates proliferation of small cell lung carcinoma cells in
      vitro via nonopioid binding sites.
AB  - The small cell lung carcinoma cell line U-1690 bound beta-endorphin via nonopioid
      binding sites also recognized by the C-terminal part of this opioid peptide Lys
      Lys-Gly-Glu, but not by opiate alkaloids such as naloxone and morphine or other
      opioid peptides. The beta-endorphin binding did not affect the production of
      cAMP, but was enhanced by dexamethasone pretreatment. The beta-endorphin
      stimulated proliferation of U-1690 cells was inhibited by Lys-Lys-Gly-Glu and
      increased by dexamethasone pretreatment. The cells also produce beta-endorphin,
      suggesting an autocrine mechanism.

PMID- 7641800
TI  - Expression of the first N-glycosylation gene in the dolichol pathway, ALG7, is
      regulated at two major control points in the G1 phase of the Saccharomyces
      cerevisiae cell cycle.
AB  - The Saccharomyces cerevisiae ALG7 gene, which functions by initiating the
      dolichol pathway of protein N-glycosylation, displays properties of an early
      growth-response gene. To initiate studies of the involvement of ALG7 in cellular
      proliferation, we have now more precisely analyzed ALG7 expression in the G1
      phase of cell cycle. We show that the rapid rate of ALG7 mRNA accumulation
      following growth stimulation was attenuated soon thereafter and that ALG7 growth
      induction occurred irrespective of alpha-factor. ALG7 growth induction was
      observed in mutants conditionally defective for reentry into the cell cycle from
      the stationary phase, indicating that the induction occurred prior to the
      performance of START. In addition, the steady-state levels of ALG7 mRNAs declined
      four-fold in response to START-I cell division arrest brought about by alpha
      factor treatment later in G1. Importantly, deregulated expression of ALG7
      resulted in an aberrant alpha-factor response. Our data not only indicate that
      ALG7 expression is regulated at two critical control points in G1 that determine
      the proliferative potential of cells, but also provide a link between ALG7 and
      START.

PMID- 7641801
TI  - Immunofluorescence localization of a 25-kDa Tetrahymena EF-hand Ca(2+)-binding
      protein, TCBP-25, in the cell cortex and possible involvement in conjugation.
AB  - The Tetrahymena Ca(2+)-binding protein of 25 kDa (TCBP-25) is a member of the
      calmodulin family containing four EF-hand Ca(2+)-binding loops, but its
      biological role has not yet been investigated. In this study, TCBP-25 was
      expressed in Escherichia coli as a glutathione S-transferase fusion protein and
      then purified. Purified TCBP-25 showed a typical Ca(2+)-dependent shift in
      electrophoretic mobility, consistent with conformational change caused by Ca(2+)
      binding. Localization of TCBP-25 was examined by indirect immunofluorescence
      using an antiserum specific for TCBP-25. Strong immunofluorescence was observed
      all over the cell cortex except in and around basal bodies. From the results of
      immunofluorescence using detergent-extracted cells, TCBP-25 is suggested to exist
      as an insoluble form in the cell cortex. TCBP-25 appears to be localized in the
      cortical alveoli or the epiplasm and exists around both the migratory and the
      stationary gametic pronuclei at the pronuclear exchange stage during conjugation.
      Therefore, we speculate that TCBP-25 may play crucial roles in Ca(2+)-mediated
      signaling processes in the cell cortex and in a Ca(2+)-dependent pronuclear
      exchange process during conjugation.

PMID- 7641802
TI  - Expression of gamma-glutamyl transpeptidase in midgestation mouse yolk sac and
      mouse visceral yolk sac carcinoma cells.
AB  - gamma-Glutamyl transpeptidase (gamma GT) is a crucial enzyme for the metabolism
      of xenobiotics and endogenous mediators of biological functions (leukotrienes,
      prostaglandins, and hepoxillins). Yet little is known about its potential role
      during development. It is a single copy gene expressed from at least seven
      promoters. Using histochemistry and immunohistochemistry we demonstrate that
      gamma GT first appears in the midgestational yolk sacs of mouse embryos.
      Established cell lines with phenotypic features of yolk sac endoderm (JC-44) or
      embryonic stem cells were also assayed for the expression of gamma GT.
      Significant levels were detected in JC-44 cells and higher levels were found in
      JC-44-derived embryoid bodies. Because this cell line appears to be a good in
      vitro counterpart of yolk sac differentiation, we characterized the gamma GT mRNA
      types expressed in JC-44 cells. By ribonuclease protection analysis, gamma GT RNA
      types IV and VI represent about 80% of the total gamma GT RNA in JC-44 embryoid
      bodies. Reverse transcription-mediated polymerase chain reaction detected low
      amounts of gamma GT RNA types I, III, and V. Expression of gamma GT in yolk sac
      follows a pattern seen in many tissues in which one or two gamma GT RNA types
      dominate the expression profile; however, the reason for this tissue specificity
      is unknown.

PMID- 7641803
TI  - The experimental homologous and heterologous separation distance histograms for
      the centromeres of chromosomes 7, 11, and 17 in interphase human T-lymphocytes.
AB  - The simultaneous 3D arrangement of the interphase centromeres of chromosomes 7,
      11, and 17 in unstimulated human T-lymphocytes is analyzed. Using triple in situ
      hybridization in combination with optical sectioning and image processing, the
      identification of three pairs of centromeres in each nucleus and the assignment
      of 3D coordinates to each centromere are made. The homologous and heterologous
      centromere separation distance histograms are determined and compared to the
      hypothesized histograms for randomly distributed centromeres. The experimental
      nuclei are truncated spheres in shape with a principal radius of 3.7 +/- 0.3
      micron and a truncated hemispherical height of 2.6 micron. None of the separation
      distance distributions appears to be statistically significantly different from a
      random model distribution.

PMID- 7641804
TI  - Prostacyclin (PGI2) synthase is a constitutively expressed enzyme in human
      endothelial cells.
AB  - Biogenesis of prostanoids is under the control of some polypeptide growth
      factors. Cytosolic phospholipase A2, a form specific for arachidonic acid
      containing phospholipids, is activated by a translocation mechanism regulated by
      growth factors, while prostaglandin H synthase isoforms are induced de novo in
      several cell types. No information is available as far as PGI2 synthase is
      concerned. Human umbilical vein endothelial cells were cultured under conditions
      favoring proliferation or differentiation or capillary-like network formation in
      the presence of collagen gels. Basic fibroblast growth factor (bFGF 0.5-4 ng/ml)
      was used as a mitogen, interleukin-1 alpha (IL-1 alpha 10-60 UI/ml) as a
      differentiating agent, and prostacyclin (PGI2) biosynthesis was evaluated. Under
      the first condition, basal PGI2 production was unaffected while, in the presence
      of IL-1 alpha, a marked stimulation of PGI2 synthesis was observed. It is known
      that IL-1 alpha is a potent inducer of PGH synthase, while it is not known
      whether PGI2 synthase is also induced. Two lines of evidence indicate that PGI2
      synthase is a constitutively expressed not inducible enzyme: (a) proliferating
      nonproducing cells when added with PGH2 produce an amount of PGI2 not different
      from the amount produced by cells stimulated with IL-1 alpha; (b) under this
      condition PGI2 synthase was immunodetectable either by immunofluorescence
      detected by confocal microscopy or by ELISA and, on microsomes isolated from
      endothelial cells, by Western blotting. It is concluded that the limiting step in
      the conversion arachidonate-PGI2 is represented solely by the level of PGH
      synthase. These results strongly suggest, but do not prove, the constitutive
      nature of the enzyme. The final demonstration requires the availability of a
      probe to detect mRNA level, a trial we are carrying out at the moment.

PMID- 7641805
TI  - Identification of a novel mitogen-inducible gene (mig-6): regulation during G1
      progression and differentiation.
AB  - We have identified a novel human gene (mig-6) that is rapidly induced upon
      mitogenic stimulation of quiescent fibroblasts. Serum induction is partially
      inhibited by protein synthesis inhibitors, indicating that mig-6 shares
      characteristics of both primary and secondary response genes. In contrast to most
      other mitogen-responsive genes, mig-6 mRNA expression is also regulated during
      normal cell cycle progression, showing a clear peak around mid-G1. Consistent
      with the regulation of mig-6 expression during the cell cycle, terminal
      differentiation of HL-60 cells to either granulocytic or macrophage-like cells
      also leads to clear changes in the levels of mig-6 mRNA. These observations
      suggest that the mig-6 gene represents a useful tool for the analysis of cell
      cycle progression and perhaps terminal differentiation. As a first step toward a
      functional characterization we show that the Mig-6 polypeptide is located in the
      cytoplasm.

PMID- 7641806
TI  - Thermal protein denaturation and protein aggregation in cells made thermotolerant
      by various chemicals: role of heat shock proteins.
AB  - Thermotolerance (TT) induced by sodium arsenite (A-TT: 100 microM, 1 h, 37
      degrees C) was compared to heat-induced thermotolerance (H-TT: 15 min, 44 degrees
      C) using HeLa S3 cells. All four pretreatments led to comparable levels of
      thermotolerance and also induced resistance to arsenite-, ethanol-, and diamide
      induced toxicity (clonogenic ability). Stress-induced expression of the major
      heat shock proteins (hsp27, hsc70(p73), hsp70(p72), and hsp90) was generally
      highest in H-TT cells and lowest in A-TT cells. Interestingly, the four types of
      TT cells showed distinct differences in certain aspects of resistance against
      thermal protein damage. Thermal protein denaturation and aggregation determined
      in isolated cellular membrane fractions was found to be attenuated when they were
      isolated from H-TT and A-TT cells but not when isolated from E-TT and D-TT cells.
      The heat resistance in the proteins of the membrane fraction corresponded with
      elevated levels of hsp70(p72) associated with the isolated membrane fractions. In
      the nuclear fraction, only marginal (not significant) attenuation of the
      formation of protein aggregates (as determined by TX-100 (in)solubility) was
      observed. However, the postheat recovery from heat-induced protein aggregation in
      the nucleus was faster in H-TT, E-TT, and D-TT cells, but not in A-TT cells.
      Despite the fact that elevated levels of hsp27, hsp70(p73), and hsp70(p72) were
      found in the TX-100 insoluble nuclear fraction derived from all TT cells, no
      correlation was found with the degree of resistance in terms of the accelerated
      recovery from nuclear protein aggregation. The only correlation between
      accelerated recovery from nuclear protein aggregates was that with total cellular
      levels of hsp27. The data indicate that heat-induced loss of clonogenic ability
      may be a multitarget rather than a single target event. A threshold of damage may
      exist in cells after exposure to heat; multiple sets of proteins in (different
      compartments of) the cell need to be damaged before this threshold is exceeded
      and the cell dies. As a consequence, stabilization of only one of these sets of
      proteins is already sufficient to render cells thermotolerant at the clonogenic
      level.

PMID- 7641807
TI  - Phagocytic activity of FRTL-5 rat thyroid follicular cells as measured by
      ingestion of fluorescent latex beads.
AB  - A rat thyroid cell line (FRTL-5) was used to study the phagocytic activity of
      thyroid follicular cells using fluorescent latex beads and flow cytometric
      analysis. Morphologic studies demonstrated that latex beads were engulfed and
      located within cytoplasmic vacuoles of thyrocytes. Flow cytometric evaluation of
      cell suspensions revealed high levels of fluorescence in cells engulfing latex
      beads. Using thyrotropin (TSH) as a stimulator of thyroid function and human
      interleukin-1 beta as an inhibitor, protocols were established for measuring the
      effects of these substances on either basal or TSH-induced phagocytosis. Cells
      exposed to latex beads over time in basal (0H) or TSH-containing medium had an
      increase in time-dependent phagocytic activity which was maximal after 24 or 8 h,
      respectively. Treatment of FRTL-5 cells with either a stimulator or an inhibitor
      revealed maximal change in phagocytic activity after 72 h as measured by the
      percentage of phagocytic cells as well as the mean fluorescence intensity.
      Phagocytic activity and iodide trapping by FRTL-5 cells were qualitatively
      similar in both sensitivity and magnitude of change in the assays used in this
      study. Phagocytosis of fluorescent latex beads represents a sensitive
      nonradioactive assay of thyrocyte function whose regulation is similar to iodide
      trapping.

PMID- 7641808
TI  - Effect of 9-cis-retinoic acid on growth and RXR expression in human breast cancer
      cells.
AB  - A number of studies have demonstrated the ability of retinoic acid (RA) to
      inhibit the growth of estrogen receptor-positive (ER+) human breast cancer cell
      lines. The precise mechanism of growth inhibition is not known. However, the
      biological effects of RA in other model systems have been shown to be mediated
      via the nuclear retinoic acid receptors (RARs) and the retinoid X receptors
      (RXRs). While several laboratories have examined the expression of RARs in
      various breast cancer cell lines, no information is available concerning the role
      of the RXRs and 9-cis-RA, the natural ligand of RXRs, in the response of breast
      cancer cells to RA. Using a representative panel of breast cancer cell lines, we
      determined the effect of 9-cis-RA on growth and cell cycle stage distribution,
      analyzed steady-state mRNA levels of RXR-alpha, -beta, and -gamma, and determined
      the effect of all-trans-RA and 9-cis-RA on RXR expression. Our results show that:
      (1) the growth of ER+/RA-sensitive breast cancer cells is inhibited by treatment
      with 9-cis-RA by blocking entry into S phase; (2) both ER+/RA-sensitive and ER
      /RA-resistant breast cancer cell lines express RXR-alpha and RXR-beta mRNAs but
      not RXR-gamma; however, levels of these transcripts did not correlate with the RA
      response; and (3) levels of RXR-alpha and RXR-beta mRNA were not significantly
      altered following treatment with either all-trans-RA or 9-cis-RA. These results
      suggest that the mechanism responsible for the retinoid sensitivity of breast
      cancer cells does not involve transcriptional modulation of the RXRs by RA.

PMID- 7641809
TI  - Effects of the disintegrin eristostatin on individual steps of hematogenous
      metastasis.
AB  - Adhesion molecules, including integrins, are important for interactions of cancer
      cells with vessel walls, a step leading to cancer metastasis. Disintegrins block
      the action of integrins by binding to them. We tested the hypothesis that the
      disintegrin eristostatin would block metastasis by interfering with cancer cell
      adhesion to vessel walls, thus preventing extravasation. Experimental metastasis
      assays, in which B16F1 melanoma cells (controls vs eristostatin-treated, 25
      micrograms/ml) were injected via mesenteric veins of anesthetized C57BL/6 mice,
      showed that eristostatin reduced (P < 0.05) the mean number of liver metastases
      from 14.4 to 0.6 at 11 days postinjection (p.i.). We examined three different
      steps in metastasis at which eristostatin could have exerted its effect, namely,
      cell arrest, extravasation, and migration. Control and eristostatin-treated B16F1
      cells were fluorescently labeled and examined by videomicroscopy in liver
      microcirculation in vivo at various times up to 14 days p.i. Measurements of
      vessel size in which cell arrest occurred and length/width ratio of arrested
      cells showed only small differences between control and eristostatin-treated
      cells. Eristostatin treatment did not prevent extravasation, and the timing and
      process of extravasation were similar for both treated and control cells; by 3-4
      days p.i. more than 90% of the cells had extravasated or were in the process.
      Eristostatin also did not affect the ability of extravasated cells to migrate
      through the extracellular matrix to the subcapsular region where tumors later
      form. Therefore, we conclude that eristostatin exerted its primary effect by
      regulating the number of individual cancer cells that grow after extravasation.

PMID- 7641810
TI  - Terminal differentiation-dependent alteration in the expression of translation
      elongation factor-1 alpha and its sister gene, S1, in neurons.
AB  - Elongation factor-1 alpha (EF-1 alpha) is a highly conserved, abundantly
      expressed protein that functions in peptide elongation during mRNA translation.
      Mammalian species contain a second EF-1 alpha gene, S1, whose expression is
      limited to brain, heart, and skeletal muscle. Such tissue specificity in S1 gene
      expression led us to hypothesize that this specialized member of the EF-1 alpha
      family is possibly essential to terminally differentiated, long-lived cells such
      as neurons, cardiomyocytes, and myocytes. We report here that during development,
      EF-1 alpha mRNA levels remain unchanged in S1-negative tissues, but sharply
      decrease in S1-positive tissues. RNase protection as well as tissue distribution
      analyses of the S1 message suggest that down-regulation of EF-1 alpha expression
      coincides well with that of S1 up-regulation during postnatal development.
      Analysis of primary cultures of the rat neonatal cerebral cortex cells has shown
      that S1 gene expression is indeed restricted to neurons only, whereas nonneuronal
      cell types such as astrocytes and microglia are S1-negative. EF-1 alpha mRNA on
      the other hand was detected in all three cell types, namely, neurons, astrocytes,
      and microglia. This report confirms the terminal differentiation-dependent
      expression of the S1 gene in neurons of the cerebral cortex.

PMID- 7641811
TI  - Higher order nuclear structure in mammalian sperm revealed by in situ
      hybridization and extended chromatin fibers.
AB  - The higher order organization of chromosomes in human and mouse sperm-cell nuclei
      has been visualized by fluorescence in situ hybridization. In mouse testicular
      sperm, centromeres form several linear higher order structures that are attached
      to a heterochromatic chromocenter at the center of the nucleus. Telomeres of the
      acrocentric mouse chromosomes are associated with either the heterochromatic
      center or the nuclear membrane. Whole chromosome domains are arranged parallel to
      the heterochromatic chromocenter and occasionally wrapped around it. We propose
      that constitutive heterochromatin serves as the nucleation point for a cell-type
      specific organization of mouse sperm chromatin. In human mature sperm, individual
      chromosomes also appear as elongated territories. When human sperm nuclei are
      lysed with high salt and detergent, the normally condensed sperm chromatin
      unravels into linear arrays that exhibit a discrete nodular substructure (of <
      300 nm diameter). These beads may represent a basic packaging unit of sperm
      chromatin. Larger superbead-like structures are also seen along the extended
      chromatin fibers and these could contain multiples of the basic packaging unit.
      These observations indicate that mammalian sperm nuclei have a highly defined
      nuclear architecture. The implications of an ordered organization of DNA in sperm
      are unknown, but it is possible that functional compartmentalization of the sperm
      cell nucleus influences the initiation and regulation of paternal gene activity
      in the early embryo.

PMID- 7641812
TI  - Induction of cyclin B and H1 kinase activity in apoptotic PC12 cells.
AB  - The present study examines whether cyclin B may be involved in apoptosis of
      neuronally differentiated PC12 cells following withdrawal of NGF. Cyclin B mRNA
      increased approximately 10-fold 4 days after NGF withdrawal, as indicated by
      competitive RT/PCR. Sequencing of the PCR product confirmed that it was derived
      from cyclin B mRNA. Cyclin B protein increased in parallel with cyclin B mRNA, as
      shown by immunoblotting. Immunoprecipitation with anti-cyclin B antibody
      demonstrated that cyclin B was associated with H1K activity, which reached a
      maximum 5 days after NGF withdrawal. When proteins immunoprecipitated with anti
      cyclin B antibody were immunoblotted with anti-PSTAIR antibody, a protein with
      apparent molecular weight of 34 kDa was detected. This protein was identified as
      p34cdc2 on the basis of immunoreactivity with antibody against the C-terminal
      portion of mouse p34cdc2. Since cyclin B/p34cdc2 complexes are known to catalyze
      chromosomal condensation and nuclear envelope breakdown during mitosis, these
      results suggest that cyclin B/p34cdc2 may play some role in the nuclear changes
      accompanying apoptosis of PC12 cells.

PMID- 7641813
TI  - Rapid inhibition of mRNA synthesis during preimplantation embryo development:
      vital permeabilization by lysolecithin potentiates the action of alpha-amanitin.
AB  - Lysolecithin was used to permeabilize embryonic cells to impermeant compounds
      without compromising embryo viability. Within 2 min of exposure to 0.05%
      lysolecithin, mouse morulae became permeable to inositol 1,4,5-trisphosphate,
      leading to the release of calcium from intracellular stores. Although these
      morulae remained permeable for at least 2 h, they developed normally to the
      blastocyst stage during subsequent culture in vitro. Lysolecithin
      permeabilization was then used to potentiate the internalization of alpha
      amanitin. Pretreatment with lysolecithin for 2 min markedly accelerated the onset
      of transcriptional inhibition from 3 h to 10 min after alpha-amanitin addition.
      The rapid inhibition by alpha-amanitin of mRNA synthesis in lysolecithin-treated
      embryos provided a precise method for delineating developmentally important
      transcriptional periods. Using this protocol, we found that mRNAs required for
      embryonic cavitation were synthesized between 87 and 91 h post-hCG, shortly
      before blastocoel formation commenced.

PMID- 7641814
TI  - Effects of epidermal growth factor and phorbol ester on thyroid epithelial
      integrity.
AB  - The effects of epidermal growth factor (EGF) and phorbol ester (tetra-O
      decanoylphorbol-16-acetate; TPA) on thyroid epithelial integrity were studied in
      filter-cultured monolayers of porcine thyrocytes, which before experiments were
      growth-arrested and had a high transepithelial resistance (RTE > 6.10(3)
      omega.cm2) and polarized, thyroid-specific functions. Both EGF and TPA stimulated
      dose-dependently the cellular incorporation of [3H]thymidine, which maximally (at
      10 ng/ml EGF for 48 h) corresponded to a 65% increase of the DNA content. The EGF
      treated cells proliferated mainly within the original monolayer, which became
      folded due to the increased cell number; clusters of epithelial cells also
      assembled between the monolayer and the filter. Although the transepithelial
      potential difference was reduced, from 15-30 mV in controls to 2-10 mV, the
      epithelial barrier function was maintained (RTE 1-3.10(3) omega.cm2;
      impermeability to [3H]inulin). EGF did not change the ultrastructural polarity of
      the plasma membrane or the distinct distribution of ZO-1 and cadherin
      immunoreactivities to junctions, but cytoplasmic cadherin present in controls
      disappeared after EGF. In cultures acutely depleted of extracellular Ca2+ EGF
      pretreatment for 48 h antagonized the preventive effect of thyrotropin on
      paracellular leakage and loss of cell-cell adhesion. TPA (0.1 microM) induced a
      temporary barrier dysfunction (maximal after 24 h) accompanied by pronounced
      alterations of cell shape and actin-based cytoskeleton, dissociation of
      junctional cadherin, and shedding of cells into the apical medium. In long-term
      (2-5 days) TPA-treated cultures the epithelial morphotype and barrier function
      recovered. The combined stimulation with EGF and TPA caused a persistent
      derangement of the cell layer including attenuation of ZO-1 at cell-cell
      contacts, paracellular leakage of [3H]inulin, and cell detachment. We conclude
      that EGF is able to release porcine thyroid epithelial cells from contact
      inhibition of growth along with intact cell polarity and tight junctions. Yet,
      when acting together with phorbol ester EGF provokes a lasting morphological
      transformation. Impaired positive control of Ca(2+)-dependent cell-cell adhesion
      in EGF-treated cultures suggests a latent defect with possible transforming
      potential in the cadherin-based regulation of the junctional complex.

PMID- 7641815
TI  - Altering the expression of cell surface beta 1,4-galactosyltransferase modulates
      cell growth.
AB  - beta 1,4-Galactosyltransferase (GalTase) is unusual among the
      glycosyltransferases in that it is localized both in the Golgi complex and on the
      cell surface. Most studies of surface GalTase function have focused on its role
      in cellular interactions; however, surface GalTase has also been suggested to
      function during cellular proliferation. Consistent with this hypothesis, a
      variety of GalTase-specific perturbants inhibit cell growth in vitro and in vivo.
      However, all of these studies have been limited to the use of exogenous reagents
      to perturb GalTase function. Furthermore, all of these perturbants inhibit cell
      growth, irrespective of whether they stimulate or inhibit GalTase enzyme
      activity. Therefore, it remains unclear whether surface GalTase delivers a growth
      inhibitory or growth stimulatory signal. In this study, we took a more direct
      approach to defining surface GalTase function during growth by examining its
      expression during the cell cycle and by molecularly altering its expression in
      stably transfected cell lines. The expression of GalTase was shown to be cell
      cycle specific, with the cell surface and intracellular GalTase pools displaying
      independent expression patterns. Furthermore, multiple, independent, stably
      transfected cell lines with reduced levels of cytoskeletally associated surface
      GalTase grew faster than control cells, whereas cell lines that over-expressed
      surface GalTase grew slower than controls. These observations directly support
      the concept that surface GalTase delivers a growth inhibitory signal. Evidence is
      presented suggesting that surface GalTase interacts with the epidermal growth
      factor (EGF) receptor, as suggested by others. The activity of the EGF receptor
      was shown to be directly proportional to the growth rate of the various GalTase
      transfected cell lines. Thus, the expression of surface GalTase directly affects
      cell proliferation rate and may do so by modulating the ability of the EGF
      receptor to transduce EGF-dependent signals.

PMID- 7641816
TI  - Monocyte chemoattractant activity of Ser195-->Ala active site mutant recombinant
      alpha-thrombin.
AB  - alpha-Thrombin is chemotactic for human monocytes with optimal activity between
      10-100 nM. The mechanism by which this response is mediated remains a point of
      controversy. The purpose of this study was to compare the chemotactic activity of
      proteolytically inactive thrombin (active site Ser195-->Ala mutant or Phe-Pro-Arg
      chloromethyl ketone-inactivated thrombin) to thrombin and the "tethered ligand"
      thrombin receptor agonist peptide SFLLRN (single-letter amino acid code).
      Monocyte chemotaxis was compared to an optimal concentration (10 nM, considered
      to be 100%) of formyl-Met-Leu-Phe (fMLP). Proteolytically inactive thrombin (38%
      of fMLP) had similar chemotactic activity to active thrombin (46% of fMLP) at a
      concentration of 100 nM. Chemotaxis to SFLLRN was comparable to that of a control
      hexapeptide (FSLNLR) which is not an agonist for the tethered ligand thrombin
      receptor. Cross-desensitization experiments showed that pretreatment of monocytes
      with either mutant or active thrombin reduced subsequent chemotaxis to both
      thrombin chemotaxins. Pretreatment with SFLLRN did not decrease subsequent
      chemotaxis to either form of thrombin. Calcium flux measurements showed that both
      active thrombin and SFLLRN induced a rapid increase in monocyte and platelet
      intracellular calcium concentration. However, there was no intracellular calcium
      change in response to mutant thrombin or FSLNLR. Likewise, active thrombin and
      SFLLRN induced a rapid net increase in polymerized actin, but mutant thrombin and
      FSLNLR did not. By contrast, both active and mutant thrombin induced a
      polarization of monocyte morphology and actin distribution. This polarization has
      been associated with directed migration in many cell types. SFLLRN, however,
      induced a symmetrical increase in polymerized actin. These results suggest that
      measurements of intracellular calcium and polymerized actin are not perfect
      surrogate tests for true chemotactic activity. These results show that thrombin
      proteolysis is not required for monocyte chemotaxis and may be mediated by
      interaction with a binding site other than the tethered ligand thrombin receptor.

PMID- 7641817
TI  - HGF/SF inhibits junctional communication.
AB  - Hepatocyte growth factor/scatter factor (HGF/SF) is a fibroblast-derived protein
      that affects the growth, motility, and differentiation of epithelial and
      endothelial cells. We have investigated the effect of HGF/SF on junctional
      communication in mouse keratinocytes (MK cells). HGF/SF inhibited cell
      communication in MK cells as assessed by the transfer of a low-molecular-weight
      dye, Lucifer Yellow. The inhibition was rapid, the earliest effects being
      apparent 5 to 10 min after addition of the factor, and was transient. The
      decrease in dye transfer correlated with a loss of the gap junction protein
      connexin 43 as measured by Western blotting, probably due to increased protein
      degradation. The results show that junctional communication is an early target of
      HGF/SF activity and they are consistent with the hypothesis that gap junctions
      are primary targets of the action of growth factors.

PMID- 7641818
TI  - Widely used enhancer of eukaryotic expression vectors is strongly and
      differentially regulated in fibroblast, myoblast, and teratocarcinoma cell lines.
AB  - The expression of transgenes in eukaryotic cells is a powerful approach in cell
      biology. In most cases, it is based on the activity of strong and constitutive
      viral cis-acting elements in eukaryotic expression vectors. Here we show that a
      widely used such element derived from an early gene of human cytomegalovirus is
      strongly and differentially regulated in mouse cell lines. We analyzed
      cytomegalovirus promoter-driven expression of stably transfected transgenes in
      growing, confluent, and differentiating mouse 3T3 fibroblasts, C2C12 myoblasts,
      and P19 teratocarcinoma cells. In the fibroblasts, transgene expression was
      strongly downregulated in confluent cultures and was upregulated in growing or
      confluent cultures by phorbol ester. In contrast, no downregulation by
      confluency, nor upregulation by phorbol ester, was detected in C2C12 cells. In
      addition, while marked upregulation was detected in differentiating myotubes,
      transgene expression was downregulated when differentiating teratocarcinoma cells
      assumed a neuronal phenotype. These results demonstrate the existence of drastic
      differences in the regulation of transgene expression in different types of cell
      lines, indicating that when studying transgene function in cells that are not
      growing exponentially, viral promoter-driven expression should not be taken for
      granted.

PMID- 7641819
TI  - Isolation and characterization of highly enriched, prefusion mouse osteoclastic
      cells.
AB  - This study describes the isolation and characterization of highly enriched
      mammalian osteoclast precursors, released by the "disintegrin" echistatin, from
      an osteoclast formation culture. Incubation of a 6-day coculture of mouse bone
      marrow cells and mouse osteoblastic cells (MB1.8) with echistatin (30 nM), an RGD
      containing snake venom, for 20 min yielded an 88-95% pure population of tartrate
      resistant acid phosphatase-positive cells, 1.5 x 10(5) cells per 150 cm2 culture
      dish. These cells were mostly mononucleated and based on the following
      characteristics are considered to be prefusion osteoclasts (pOC cells): (i)
      presence of calcitonin (CT) receptors documented by 125I-sCT autoradiography and
      cAMP generation in response to salmon calcitonin; (ii) expression of mRNAs for
      alpha v beta 3 integrin, osteopontin, 92-kDa type IV collagenase (matrix
      metalloproteinase 9), carbonic anhydrase II, OC-2 (an "osteoclastic" cysteine
      proteinase), and protein tyrosine phosphatase epsilon; and (iii) high level
      expression of pp60c-src protein. The pOC cells resorb bone (form "pits" on bone
      slices) but only in the presence of osteoblastic MB1.8 cells and 1,25(OH)2D3.
      Resorption was inhibited by CT. In conclusion, we describe a rapid, reproducible
      procedure to isolate virtually pure mammalian prefusion osteoclasts, which should
      help in the study of osteoclast formation, composition, and function.

PMID- 7641820
TI  - Lamin dynamics during sea urchin male pronuclear formation in vitro.
AB  - The dynamics of lamin disassembly and reassembly during sea urchin male
      pronuclear development in vitro was investigated. Using five anti-lamin
      antibodies, we monitored by immunofluorescence and immunoblotting the changes in
      lamins during sperm chromatin decondensation, nuclear envelope (NE) formation,
      and male pronuclear swelling in fertilized sea urchin egg cytoplasmic extracts.
      We report the existence of five proteins in sperm nuclei and swollen male
      pronuclei (p49, p54, p65, p72, p84) which react with the antibodies. The sperm
      antigens resist membrane permeabilization with lysolecithin and 0.1% Triton X
      (TX)-100, but are removed from the lateral aspects of the nuclei by 1% TX-100.
      All five are completely removed from nuclei within 10 min of incubation in egg
      extracts. Initial chromatin decondensation and NE formation occur without
      reassembly of the putative lamins, but all lamins or lamin epitope-containing
      peptides assemble coordinately during pronuclear swelling promoted by adenosine
      5'-triphosphate. Of the five pronuclear antigens, p49 and p54 appear to originate
      exclusively from the sperm. p65, p72, and p84 are also present in the egg
      cytoplasm and may be contributed to pronuclei by either source. Assembly of
      putative lamins and nuclear swelling, but not chromatin decondensation and
      nuclear envelope formation, are prevented in lamin-depleted cytoplasmic extracts.
      Our results indicate that p49 and p54 are not necessary for nuclear swelling,
      cytoplasmic p65 is required for swelling, and p72 and p84 are by themselves not
      sufficient but may be involved with p65 in nuclear swelling and full pronuclear
      development in vitro.

PMID- 7641821
TI  - G protein function during biomembrane fusion in Dictyostelium: presence and
      importance of a G alpha s subunit during fertilization and phagocytosis.
AB  - Previous work has shown that GTPase function is essential for fertilization and
      cannibalistic phagocytosis during the sexual development of Dictyostelium
      discoideum. In this work, the importance of heterotrimeric G proteins during
      these events was established further using aluminum fluoride which inhibited both
      fertilization and cannibalistic phagocytosis, as well as the phagocytosis of
      bacteria by vegetative amoebae. Using distinct immune sera directed against the
      amino terminus and the carboxy terminus of mammalian G alpha s, we have provided
      unique evidence for a G alpha s subunit of approximately 55 kDa in D. discoideum
      (referred to as dG alpha s). Furthermore, this protein localizes to the membranes
      of fusing cells as well as to both vegetative and zygote giant cells, indicating
      that it might function during fertilization as well as during both vegetative
      (i.e., bacterial) and cannibalistic (i.e., amoebal) phagocytosis. During its down
      regulation in nonphagocytic cells new isozymes of dG alpha s appear, suggesting
      that it may be posttranslationally modified. Having identified a putitive G alpha
      s homologue, this work has set the stage for further investigations into its
      function in Dictyostelium.

PMID- 7641822
TI  - Albumin synthesis by rat hepatocytes cultured on collagen gels is sustained
      specifically by heparin.
AB  - We investigated the influence of various kinds of glycosaminoglycans (GAGs) in
      collagen gels on the maintenance of albumin synthesis in primary culture of rat
      hepatocytes. Among the GAGs examined (heparin, heparan sulfate, keratan sulfate,
      chondroitin sulfate A, dermatan sulfate, and hyaluronic acid), only heparin
      containing collagen gel cultures could significantly sustain albumin synthesis.
      However, other GAGs, such as heparan sulfate and keratan sulfate, had almost no
      effect on the maintenance of albumin synthesis. Heparin in collagen gels
      exhibited a dose-dependent effect on albumin synthesis: heparin at 400
      micrograms/ml-collagen solution maintained albumin synthesis for over 3 weeks. On
      the other hand, when an equivalent amount of heparin was added directly to the
      collagen gel culture medium, it prolonged albumin synthesis for only 10 days. The
      results demonstrate that specific regulation of albumin synthesis by heparin was
      significantly promoted by coincubating it with collagen, suggesting that some
      specific interaction between heparin and collagen might be of importance for the
      maintenance of hepatocyte functions.

PMID- 7641823
TI  - Characterization of verocytotoxin-producing Escherichia coli O157 isolates from
      patients with haemolytic uraemic syndrome in Western Europe.
AB  - Fifty verocytotoxin (VT)-producing Escherichia coli (VTEC) strains of serogroup
      O157 were characterized by phage typing, polymerase chain reaction (PCR) for VT
      genes and the E. coli attaching and effacing (eae) gene, and random amplified
      polymorphic DNA-PCR (RAPD-PCR) fingerprinting. The collection represented
      isolates obtained from patients with diarrhoea-associated haemolytic-uraemic
      syndrome (D+ HUS) and their family contacts, isolated in the Netherlands, Belgium
      and Germany between 1989 and 1993. Based on isolates from separate families (n =
      27) seven different phage types were identified, types 2 (44%) and 4 (33%) were
      predominant. Eighty-five percent of the strains contained only VT2 gene sequences
      and 15% both VT1 and VT2. All strains of the dominant phage types 2 and 4 carried
      the VT2 gene. Strains that belonged to the minor phage types 8, 14, 32 carried
      both VT1 and VT2 genes, with the exception of two isolates identified as phage
      types 49 and 54 which contained only VT2 genes. All O157 VTEC strains possessed
      the chromosomally-located eae gene, which indicates its usefulness as virulence
      marker. RAPD-PCR fingerprinting identified four distinct banding patterns, with
      one profile found among 79% of the strains. Based on the combined results of all
      typing methods used in this study, the collection of 50 O157 VTEC strains could
      be divided into nine distinct groups. Strains isolated from different persons
      within one family could not be distinguished by any of these methods. The data
      suggest that O157 VTEC strains are members of one clone that has become widely
      distributed.

PMID- 7641824
TI  - Application of pulsed field gel electrophoresis to the 1993 epidemic of whooping
      cough in the UK.
AB  - The purpose of this study was to DNA fingerprint the majority (64%) of isolates
      received at the Pertussis Reference Laboratory during the 1993 whooping cough
      epidemic by pulsed field gel electrophoresis of Xba I-generated restriction
      digests. Two DNA restriction patterns, types 1 and 3, predominated (40% and 23%,
      respectively, of 180 isolates) but type 2, identified in a previous study was
      notably absent. Twenty-one new DNA types occurred (24% of isolates), some being
      atypical as bands 155-230 kb were no longer conserved, but there was no
      statistically significant difference in their incidence in the upswing (June
      September) compared to the downswing (October-December) phase of the epidemic.
      There was a relatively high proportion of new types, compared to type 1, at the
      peak (September). About 50% of isolates received were from the North Western
      Region, where 44% of isolates were DNA type 1. Whereas only 1 out of 10 isolates
      from Scotland were of this type, suggesting some geographic variation.
      Statistically significant findings included a higher proportion of isolates from
      female patients (P < 0.01), most marked in the 12-24 months age group (P < 0.05);
      a higher proportion of infants under 12 months requiring hospital admission
      compared to older children (P < 0.05); and a greater number of isolates from
      unvaccinated children (P < 0.01). Analysis of serotype according to four age
      groups (under 3 months, 3-12 months, 12-24 months and above 2 years) showed
      statistically significant differences (P < 0.05) with a noticeably lower
      proportion (38%) of serotype 1,3 in 3-12 months age group and higher prevalence
      (74%) of serotype 1,3 in the 12-24 months age group. There was no correlation
      between DNA type and serotype.

PMID- 7641825
TI  - An outbreak of waterborne cryptosporidiosis associated with a public water supply
      in the UK.
AB  - In November and December 1992, an outbreak of waterborne cryptosporidiosis
      occurred in Bradford, a city in the North of England. In all 125 cases were
      involved, the majority of whom lived in part of the city which received its
      drinking water supply from a single water treatment works. A case control study
      demonstrated an association between illness and the consumption of tapwater from
      this source; those drinking large volumes being more likely to have been ill.
      Treated water from the defined source yielded cryptosporidial oocysts. Heavy
      rainfall was recorded in the catchment area of the reservoir supplying raw water
      to the treatment works, immediately prior to the probable time of infection,
      based on dates of onset of illness.

PMID- 7641826
TI  - Tuberculosis in inner London: evidence for an increase in young adults and
      immigrants.
AB  - We report a marked increase in the rate of notifications of tuberculosis in young
      adults in the London Borough of Lambeth. Analysis of notifications made to the
      Proper Officer over a 10-year period showed that the age specific notification
      rate in the cohort aged 20-44 years increased from 30/100,000 in 1983 to
      51/100,000 in 1992. Analysis of St. Thomas' Hospital laboratory records of
      patients seen between 1984 and 1991 from whom Mycobacterium tuberculosis was
      isolated showed an increase in the number of patients of African origin from five
      in the first half of the study period (1984-7) to 25 in the second half (1988
      91): 21 of these 25 had immigrated into England within 4 years of their illness.
      This finding is being further investigated in a prospective study of ethnicity,
      travel history and date of immigration of Lambeth residents notified with
      tuberculosis.

PMID- 7641827
TI  - Interpretation of serological surveillance data for measles using mathematical
      models: implications for vaccine strategy.
AB  - Serological surveillance of measles immunity has been carried out in England
      since 1986/7. Results from sera collected in 1989-91 revealed that the proportion
      of school age children who were susceptible to measles was increasing, following
      the introduction of the measles, mumps and rubella vaccination programme in
      October 1988. Mathematical models are used to interpret these data and determine
      whether this increasing susceptibility is sufficient to allow a resurgence of
      disease from the low levels achieved by 1993. The models summarize serological
      profiles by a single parameter, the reproduction number R, which quantifies the
      level of herd immunity in the population. Results showed that there was cause for
      concern over the levels of susceptibility to measles, with an epidemic of over
      100,000 cases likely in 1995/6. These predictions are consistent with trends in
      the incidence and age distribution of measles and have enabled the planning of a
      major vaccination campaign.

PMID- 7641828
TI  - The Public Health Laboratory Service national case-control study of primary
      indigenous sporadic cases of campylobacter infection.
AB  - The aetiology of sporadic campylobacter infection was investigated by means of a
      multicentre case-control study. During the course of the study 598 cases and
      their controls were interviewed. Conditional logistic regressional analysis of
      the data collected showed that occupational exposure to raw meat (odds ratio [OR]
      9.37; 95% confidence intervals [CI] 2.03, 43.3), having a household with a pet
      with diarrhoea (OR 2.39; CI 1.09, 5.25), and ingesting untreated water from
      lakes, rivers and streams (OR 4.16; CI 1.45, 11.9) were significant independent
      risk factors for becoming ill with campylobacter. Handling any whole chicken in
      the domestic kitchen that had been bought raw with giblets, or eating any dish
      cooked from chicken of this type in the home (OR 0.41-0.44; CI 0.24, 0.79) and
      occupational contact with livestock or their faeces (OR 0.44; CI 0.21, 0.92) were
      significantly associated with a decrease in the risk of becoming ill with
      campylobacter.

PMID- 7641829
TI  - Prevalence of hepatitis A antibody among disadvantaged gypsy children in northern
      Spain.
AB  - The prevalence of antibody to hepatitis A virus (HAV) in a group of socially and
      economically disadvantaged Spanish gypsy children was compared to that of a group
      of non-gypsy middle-class children. The study included 438 children, 73 gypsies
      (38 girls and 35 boys, mean age 8.5 years, age range 2-16 years) and 365 non
      gypsy controls, randomly selected by age. The presence of anti-HAV was
      investigated using ELISA. Among the gypsy children, 82% had antibodies to HAV
      compared with 9.3% of the children in the control group. The unfavourable living
      conditions of the gypsy population (e.g. homes with poor sanitary conditions,
      overcrowding) may explain the high prevalence of HAV infection. These findings
      underline the need for specific action which targets disadvantaged populations.

PMID- 7641830
TI  - An outbreak of viral gastroenteritis associated with adequately prepared oysters.
AB  - Over Christmas 1993, an outbreak of food poisoning occurred among guests in a
      hotel in South West Scotland. Evidence from a cohort study strongly suggested
      that raw oysters were the vehicle for infection, probably due to a Small Round
      Structured Virus (SRSV). Detailed enquiry about the source and preparation of the
      oysters revealed no evidence of any unsafe handling at any stage in the food
      chain, nor any evidence of bacterial contamination. It is suggested that the
      present standards of preparation and monitoring are inadequate to protect the
      consumer, and that bacteriophage monitoring may be a useful method of screening
      for viral contamination in future.

PMID- 7641831
TI  - Hand-genital transmission of genital warts? An analysis of prevalence data.
AB  - The role of hand-genital transmission in the aetiology of genital warts is
      unclear. However this route is suggested by a number of observations including
      the relatively high proportion of genital warts in children which contain HPV
      types 1-4 (15% for children and 2% for adults). We compared two transmission
      models; one which assumes that hand-genital transmission occurs and one that it
      does not, and determined the conditions in which each model can reflect the
      available prevalence data. Hand-genital transmission provides a simple
      explanation of the observed differences in the proportions of genital warts
      containing HPV types 1-4 and 6/11 in children and adults. If hand-genital
      transmission does not occur, the observed difference could only be explained by
      an eightfold greater probability of transmission to children of types 1-4 than
      types 6/11, or by an eightfold greater duration of infection with types 1-4. Our
      findings provide support for the view that genital warts may be transmitted by
      hand-genital contact.

PMID- 7641832
TI  - Evidence for a high prevalence of spotted fever group rickettsial infections in
      diverse ecologic zones of Inner Mongolia.
AB  - A 3-year study of spotted fever group rickettsial ecology in Inner Mongolia
      revealed that nearly half of the human population tested had antibodies to
      Rickettsia sibirica detected by complement fixation test. Infected persons, ticks
      and a high proportion of seropositive livestock and wild rodents were found in
      all five vegetation zones (desert, steppe, forest, forest-grassland and
      grassland).

PMID- 7641833
TI  - Serological evidence for the reservoir hosts of cowpox virus in British wildlife.
AB  - The reservoir host of cowpox virus in Western Europe is not known, but
      epidemiological evidence from human and feline infections indicates that the
      virus is probably endemic in small wild rodents. Therefore, serum and tissue
      samples were collected from a variety of wild British mammals and some birds, and
      tested for evidence of Orthopoxvirus infection. Antibody reacting with cowpox
      virus was detected in 9/44 (20%) bank voles (Clethrionomys glareolus), 8/24 (33%)
      field voles (Microtus agrestis), 17/86 (20%) wood mice (Apodemus sylvaticus) and
      1/44 house mice (Mus musculus), but in no other animal species tested. Although
      virus was not isolated from any animal, this serological survey, together with
      other evidence, suggests that bank and field voles and wood mice are the main
      reservoir hosts of cowpox virus in Great Britain.

PMID- 7641834
TI  - Cryptosporidiosis reservoir in wild brown rats (Rattus norvegicus) in the UK.
AB  - Rats (n = 73) were trapped from nine rural farms around Oxfordshire and faeces
      were examined using the auramine-phenol and the Modified Ziehl-Neelsen
      techniques. Cryptosporidium parvum oocysts were detected in the faeces from 46
      (63%) rats. This suggests that wild rats represent a risk to human and livestock
      health through the carriage and transmission of this zoonotic protozoan.

PMID- 7641835
TI  - Infecting dose and severity of typhoid: analysis of volunteer data and
      examination of the influence of the definition of illness used.
AB  - Data from volunteers challenged with Salmonella typhi were reanalysed to explore
      the relationship between challenge dose and severity of disease. Among 120 ill
      volunteers who received between 10(5) and 10(9) organisms, dose was weakly
      correlated with peak temperature (r = 0.22, 95% CI 0.04-0.39), duration of
      temperature above 103 degrees F (39.4 degrees C: r = 0.13, 95% CI - 0.03 to 0.55)
      and symptom score (r = 0.27, 95% CI 0.09-0.43). The association with symptom
      score was lost after adjusting for year, and the findings depended on the
      definition of illness used: with stricter definitions the associations with
      temperature were also lost. The study shows the need for caution in interpreting
      the relationship between dose and severity of disease.

PMID- 7641836
TI  - A pseudo-outbreak of salmonellosis.
AB  - during July 1991, a single laboratory reported an increased number of an unusual
      salmonella isolate. An outbreak control team was convened. A case was defined as
      an individual with diarrhoea from whose faecal sample Salmonella hadar was
      isolated after 1 July 1991. By 30 July, 90 isolates had been identified and 57
      persons interviewed including 39 primary cases. Interviews failed to identify any
      common features among the cases. A review of the laboratory procedures revealed
      that the selenite enrichment medium was inoculated using the spoon from the stool
      collection kit after it was used to emulsify the faecal sample with saline for
      microscopy. Salmonella hadar was isolated from this saline. Once this practice
      was stopped, no further isolates of S. hadar were made. This pseudo-outbreak is a
      powerful reminder to verify the existence of an outbreak, especially when
      epidemiological data are inconsistent.

PMID- 7641837
TI  - Distribution of Aeromonas phenospecies and genospecies among strains isolated
      from water, foods or from human clinical samples.
AB  - A total of 332 Aeromonas spp. originating from drinking water (n = 75), fresh
      water (n = 57), chicken and ground beef (107), human faecal samples in
      association with travelling (n = 49), human faecal samples not associated with
      travelling (n = 38), and six strains from human blood cultures were studied by
      phenotypic methods and by using analysis of ribopatterns as a molecular method
      for the identification of the 13 known hybridization groups (HGs). Also included
      were the reference strains of each HG. A. hydrophila HG 1, A. caviae HG 4 and A.
      veronii biotype sobria HG 8/10 were the most important genospecies identified in
      human faecal samples. A. hydrophila HG 2 and A. media HG 5B predominated in
      drinking water and A. hydrophila HG 2 and HG 3, A. media HG 5A and HG 5B
      predominated in fresh water. In drinking water only one isolate was A. hydrophila
      HG 1 and two isolates were A. caviae HG 4. Clinically important Aeromonas spp. HG
      1 (A. hydrophila), HG 4 (A. caviae) and HG 8/10 (A. veronii biotype sobria) were
      common in chicken and ground beef. In contrast to the drinking water samples, HG
      5A was common in chicken and ground beef samples. Atypical, unidentified isolates
      were most often found in fresh water samples (12/57 strains). Although water has
      been suspected of being an important source of human aeromonas infections,
      clinically important HGs were found to be in the minority among Aeromonas spp.
      identified in drinking water or fresh water. The distribution of Aeromonas spp.
      HGs among drinking water, chicken and ground beef samples was also different,
      suggesting that contamination of meat or chicken may not originate from water.

PMID- 7641838
TI  - Carriage of Staphylococcus aureus among 104 healthy persons during a 19-month
      period.
AB  - The present study was undertaken to investigate the frequency of the nasal
      carrier rate of Staphylococcus aureus. The investigation was performed on 104
      healthy persons. The total number of swabs performed was 1498 and this resulted
      in isolation of 522 S. aureus strains. All strains have been identified, tested
      for antibiotic susceptibility, and phage-typed. The carrier-index (number of
      positive swabs/number of total swabs for each individual person) was compared
      with different sampling and culturing methods, phage type, age, and resistance to
      antibiotics. There was statistical difference in carrier rate according to sex (P
      < 0.05). Among the 104 persons 15 (14.4%) were persistent carriers, 17 (16.3%)
      intermittent carriers, 55 (52.9%) occasional carriers and 17 (16.3%) non
      carriers. Among intermittent and occasional carriers the phage-type distribution
      was different from the S. aureus strains isolated from Danish hospitalized
      patients in 1992, while the persistent carriers had similar phage-type
      distribution.

PMID- 7641839
TI  - Control of infection with multiple antibiotic resistant bacteria in a hospital
      renal unit: the value of plasmid characterization.
AB  - An outbreak of infections due to multiple antibiotic-resistant bacteria took
      place over a period of approximately 18 months in a renal unit. Strains of
      Escherichia coli, Enterobacter aerogenes, Klebsiella pneumoniae, Citrobacter spp.
      and Pseudomonas spp. were involved, and a variety of antibiotic resistances was
      encountered. Closely related plasmids encoding resistance to aztreonam,
      ceftazidime and piperacillin, possibly derived from an archetypal plasmid of 105
      kb were found in the majority of isolates examined. After limiting the use of
      aztreonam the incidence of new patient isolates of multiple-resistant organisms
      was greatly reduced. This study demonstrated how molecular studies can contribute
      to the control of an outbreak situation in a hospital unit by providing an
      impetus to reduce the use of specific antibiotics.

PMID- 7641840
TI  - Relationship between Legionella spp. and antibody titres at a therapeutic thermal
      spa in Portugal.
AB  - The presence of Legionella spp. in the water of a Portuguese spa was ascertained
      during the spa season, between May and November. Simultaneously the prevalence of
      anti-legionella antibodies in people attending the spa was also investigated. The
      antibody titres of 172 randomly selected patients and 42 therapists were
      determined, and compared with a control group of 503 blood donors. Legionellae
      were present in the spa water at low concentrations, generally lower than 10(3)
      c.f.u./l. A total of 92 strains representing eight different species or
      serogroups were isolated; the predominant isolates belonged to Legionella
      pneumophila serogroup 6 and to L. londiniensis. During the study, no clinical
      cases of Legionnaires' disease were observed, and the antibody titres were
      generally low in the groups studied. However, the antibody titres of the patients
      increased slightly during their stay at the spa, approaching the values for the
      therapists. Mean antibody titres in the groups related with the spa were
      significantly higher than those in the blood donors against five of the seven
      legionella antigens tested. The largest number of elevated antibody titres in the
      exposed groups were to the L. pneumophila sg 5 and sg 6 antigens.

PMID- 7641841
TI  - Epidemiology of invasive Haemophilus influenzae infections in England and Wales
      in the pre-vaccination era (1990-2).
AB  - This survey defined the pattern of invasive Haemophilus influenzae infections
      during 1990-2 in six regions in England and Wales during the pre-vaccination era
      providing a baseline against which any changes in patterns of disease due to the
      introduction of the Haemophilus influenzae type b vaccination programme can be
      monitored. A total of 946 cases of invasive Haemophilus influenzae were recorded
      during the survey period of which almost 90% were due to type b and most of the
      remainder were non-typeable. Type b infections occurred predominantly in children
      less than 5 years of age (88%) with the highest attack rate in male infants in
      the 6-11 month age group. Diagnostic category varied with both age and serotype;
      meningitis was the commonest presentation overall but pneumonia and bacteraemia
      were more common in adults and non-typeable isolates. Mortality was highest in
      neonates and the elderly (over 65 years of age) who were more likely to have an
      underlying predisposing condition than older children and adults. Children under
      5 years of age had a higher case fatality rate for non-typeable than for type b
      infections. Ampicillin resistance was 15% and there were no cefotaxime resistant
      type b isolates.

PMID- 7641842
TI  - Monoclonal antibodies against CD54 (ICAM-1) and CD11a (LFA-1) prevent and inhibit
      endotoxin-induced uveitis.
AB  - We studied the effect of monoclonal antibodies (mAbs) against CD54 (intercellular
      adhesion molecule-1; ICAM-1) and CD11a (lymphocyte function-associated antigen-1;
      LFA-1) on the prevention and treatment of endotoxin-induced uveitis (EIU). When
      treated at the time of endotoxin injection the mean number of inflammatory cells
      infiltrating the eye +/- S.E.M. on histologic sections was 469.2 +/- 51.9 for
      controls, 13.8 +/- 2.6 for rats receiving anti-ICAM-1 mAb (P < 0.0001), and 195.8
      +/- 48.8 for rats receiving anti-LFA-1 mAb (P = 0.0003). When treated after the
      start of inflammatory disease, the mean number of infiltrating inflammatory cells
      +/- S.E.M. was 273.0 +/- 30.7 for controls, 6.4 +/- 1.7 for rats receiving anti
      ICAM-1 mAb (P < 0.0001), and 54.2 +/- 7.6 for rats receiving anti-LFA-1 mAb (P <
      0.0001). The mean number of cells per milliliter of aqueous humor +/- S.E.M. was
      1867.6 +/- 321.8 for controls, 21.7 +/- 5.3 for rats receiving anti-ICAM-1 mAb (P
      < 0.0001), and 295.1 +/- 71.2 for rats receiving anti-LFA-1 mAb (P < 0.0001).
      MAbs against ICAM-1 and LFA-1 significantly inhibited the development of EIU and
      were effective in treating clinically evident ocular inflammatory disease.

PMID- 7641843
TI  - Effects of gamma radiation on the OM431 human ocular melanoma cell line.
AB  - In order to determine the dose responsiveness to radiation of ocular melanoma, we
      conducted an in vitro dose-response study on a monolayer cell culture using a
      clonogenic assay. The effects on cell survival were determined relative to
      unirradiated controls. A human epithelioid ocular melanoma cell line, OM431, was
      maintained in tissue culture and serial dilutions of viable cells were plated in
      flasks, allowed to settle and attach for 48 h, and subsequently irradiated with 1
      10 Gy in single fractions. After 2 weeks, the number of reproducing clones
      (forming colonies with greater than 32 cells or five generations) were counted.
      The surviving fractions of cells were plotted on a cell survival curve using the
      linear quadratic model. The survival curve showed a large initial shoulder
      followed by an exponential decline in growth. Our data suggest that the OM431
      ocular melanoma cell line responds to irradiation in a manner similar to other
      melanoma cell lines and is relatively radioresistant especially at lower doses.

PMID- 7641844
TI  - Isoforms of platelet-derived growth factor and its receptors in epiretinal
      membranes: immunolocalization to retinal pigmented epithelial cells.
AB  - Epiretinal membranes (ERMs) form on the inner surface of the retina in
      conjunction with various ocular disease processes, but the factors controlling
      their development are not understood. The predominant cell types involved are
      retinal pigmented epithelial (RPE) cells and retinal glia. Cultured RPE cells
      secrete platelet-derived growth factor (PDGF), which is chemotactic and mitogenic
      for both RPE cells and retinal glia and, therefore, could be involved in the
      development of ERMs. In the present study, we performed immunohistochemical
      staining for PDGF A chain (PDGF-A), PDGF B chain (PDGF-B), and both types of PDGF
      receptors (PDGFr alpha and PDGFr beta) on ERMs associated with various disease
      processes. PDGF-A is detected in most ERMs, regardless of the associated disease
      process, and it appears to be localized predominantly in RPE cells, recognized by
      the presence of pigment and the immunohistochemical demonstration of some or all
      of the following RPE-associated epitopes: class III beta-tubulin, keratin, the 65
      kDa microsomal protein recognized by the RPE9 antibody, and cellular
      retinaldehyde-binding protein. PDGF-B is found only in minor subpopulations of
      cells in about half of the ERMs evaluated and, with only occasional exceptions,
      appears to be localized almost entirely in blood-borne cells found in and around
      vessels in vascularized ERMs. Both PDGFr alpha and PDGFr beta are demonstrated in
      most ERMs with neither isotype consistently predominating: they are found
      predominantly on RPE cells with many cells expressing both receptor types. ERMs
      with little or no RPE cell component contain little or no PDGF and PDGF receptor,
      whereas those in which the RPE cell represents the major cell type, have
      widespread PDGF and PDGF receptor positivity. These findings show that RPE cells
      in ERMs produce PDGF-A and PDGF alpha and PDGF beta receptors and suggest that
      autocrine and paracrine stimulation with PDGF may be involved in ERM
      pathogenesis.

PMID- 7641845
TI  - Isoenzymic patterns of tyrosinase in the rabbit choroid and retina/retinal
      pigment epithelium.
AB  - Tyrosinase in crude extracts from the adult rabbit choroid and retina/retinal
      pigment epithelium was found to be differently affected by the inhibitors sodium
      metabisulfite, cyanide, diethyldithiocarbamate and 2,2'-dipyridyl:the latter
      inhibited the activity in the retina/retinal pigment epithelium extract after 24
      hr of incubation, but not that in the choroid. The first three inhibitors, on the
      other hand, inhibited the activity in the choroid extract, but not in the
      retina/retinal pigment epithelium extract, after 3 hr of incubation. Both
      extracts contained one insoluble and two soluble isoenzymes. The mobilities and
      the apparent molecular weights of the soluble isoenzymes (more markedly so for
      the most rapidly migrating) differed, as revealed by polyacrylamide gel
      electrophoresis, resulting in distinct isoenzymic patterns. We suggest that such
      patterns may be related to the characteristic melanogenic features of the
      retina/retinal pigment epithelium and choroid.

PMID- 7641846
TI  - Phosphatidylethanolamine N-methyltransferase activity in isolated rod outer
      segments from bovine retina.
AB  - Phosphatidylcholine (PC) can be synthesized in isolated rod outer segments from
      bovine retina by successive transfer of methyl groups from S-adenosyl-L
      methionine (SAM) to phosphatidylethanolamine (PE), with the intermediate
      formation of phosphatidyl-N-monomethylethanolamine (PMME) and phosphatidyl-N,N
      dimethylethanolamine (PDME). This reaction is time-protein-and SAM concentration
      dependent. Phosphatidylethanolamine N-methyltransferase (PE N-MTase) has two pH
      optima, 8.5 and 10, at low (10 microM) and high (200 microM) SAM concentrations
      and requires magnesium ions for full activity. When ROS membranes were incubated
      at 5 to 200 microM SAM concentrations at pH 8.5 or pH 10, the major methylated
      product was PMME, followed by PC and PDME. The apparent Kms for SAM at pH 8.5 and
      at pH 10 were similar (37 and 38 microM, respectively). The Vmax was 13 pmol h-1
      (mg protein)-1 at pH 8.5 and 12.50 pmol h-1 (mg protein)-1 at pH 10. Pulse-chase
      experiments demonstrated a precursor-product relationship with [3H]PC as the end
      product. The level of PE N-Mtase activity in the purified ROS preparation
      obtained from crude ROS fractions by discontinuous sucrose gradient
      centrifugation, was as high as 65% of the level found in the microsomal fraction
      obtained from the remainder of the retinas. The presence of microsomal and
      mitochondrial marker enzymes, however, was minimal in the ROS preparation. The
      radioactivity incorporated into ROS PC was measured in an upper and lower band of
      PC obtained by two-dimensional TLC. We found that the amount of [methyl-3H]
      groups incorporated into the upper PC band was 2.5-fold greater than that
      incorporated into the lower one. The fatty acid composition of the upper band was
      very different from that of the lower band, the former being enriched in very
      long-chain polyunsaturated fatty acids and the latter in saturated fatty acids.
      Phosphatidyl-ethanolamine N-methyltransferase activity increased in the presence
      of exogenous phospholipid substrates. PDME being augmented ten-fold and PC eight
      fold when the incubations were carried out in the presence of PMME and PDME,
      respectively. At a 2 mM concentration, S-adenosyl-L-homocysteine (SAH) inhibited
      the methyl groups' incorporation into the endogenous phospholipids by 40%. When
      ROS membranes were selectively depleted of soluble or peripheral and soluble
      proteins, the PE N-MTase activity remained mainly associated to the membrane,
      suggesting that this enzyme (s) is an intrinsic membrane protein.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7641847
TI  - Localization of a fatty acid binding protein and its transcript in the developing
      chick retina.
AB  - The undifferentiated chick retina has elevated levels of fatty acid binding
      protein (R-FABP) mRNA. Tissue maturation is accompanied by a 50-100-fold decrease
      in transcript levels. To determine the location of the R-FABP transcript and its
      encoded protein in the developing retina, in situ hybridization and
      immunohistochemical analyses were carried out using chick embryos at different
      stages of development. The R-FABP mRNA and protein were found throughout the
      retina from day 3 to day 7 of incubation. Accumulation of R-FABP in the neurites
      of ganglion cells could readily be detected at early developmental stages. By day
      11, R-FABP transcript levels were considerably reduced in the retina, while the
      protein was primarily found in the inner nuclear layer, inner plexiform layer and
      optic nerve fiber layer of the retina. As well, R-FABP mRNA and protein were
      abundant in the non-pigmented ciliary epithelium, which represents the forward
      prolongation of the retina in the anterior eye. Immunoelectron microscopy
      revealed the presence of R-FABP in both the nucleus and cytoplasm of day 4
      retinal cells. In the day 13 retina, R-FABP was abundant in the processes of
      neuronal cells. These results suggest that, early in retinal development, there
      is a requirement for FABP in the nucleus as well as the cytoplasm of all retinal
      cells. At later stages, the concentration of R-FABP in the processes of neuronal
      cells would suggest a biochemical or structural role related to neurite extension
      and synapse formation.

PMID- 7641848
TI  - Increased release of immunoreactive calcitonin gene-related peptide (CGRP) in
      tears after excimer laser keratectomy.
AB  - The purpose of the study was to quantify the neuropeptide calcitonin gene-related
      peptide (CGRP) in normal human tear fluid and to determine the effect of
      photorefractive excimer laser keratectomy (PRK) on its release in tears. CGRP was
      assayed in tear fluid samples using an enzyme immunoassay (detection limit 0.2
      micrograms ml-1). Tear-fluid samples were collected preoperatively, 1, 2 and 7
      days after PRK and analysed for CGRP. The changes in tear-fluid secretion were
      also monitored. The intra-assay variation was 3.0-7.0%. Despite the marked
      hypersecretion of tears, the concentration of CGRP did not decrease following PRK
      indicating a concomitant increase in CGRP release by sensory nerves and/or
      lacrimal gland(s). Consequently, the release of CGRP in tears increased from
      197.9 +/- 36.6 ng min-1 (mean +/- S.E.M.) to 1723.0 +/- 402.4 ng min-1 (P < 0.01)
      on day 1, and to 2304.2 +/- 561.1 ng min-1 (P < 0.01) on day 2. On day 7, only
      minor elevation (377.02 +/- 83.24 ng min-1) was observed. It is concluded that
      CGRP is a component of normal human tear fluid. The ocular irritation response
      related to the photoablation induces an enhanced release of CGRP in tears. As a
      compound present in corneal sensory nerves CGRP may have a role in wound-healing.

PMID- 7641849
TI  - Transferrin secretion by lens epithelial cells in culture.
AB  - Transferrin (Tf), the plasma iron transport protein which supports cell
      proliferation and differentiation and has bacteriostatic, antioxidant and anti
      inflammatory activity, has been found in relatively high concentrations in the
      intraocular fluids. Intraocular synthesis of Tf has recently been demonstrated,
      although the intraocular tissue(s) responsible have not been identified. We
      designed this study to determine whether certain ocular tissues can make and
      secrete transferrin. Transferrin content of aqueous and vitreous humors and whole
      lenses was determined by ELISA. Transferrin secretion by cultured epithelia from
      lens and ciliary body was also measured. In addition, Northern blots of RNA from
      cultured lens epithelial cells, ciliary body pigmented and non-pigmented
      epithelial cells, and from whole iris, ciliary body and retina were probed with
      riboprobes for Tf mRNA and 18S rRNA. Transferrin made up 23% and 16% of total
      canine aqueous and vitreous protein. All ocular tissues and cultured cells tested
      contained mRNA for Tf, however Tf was secreted into the bathing medium from lens
      epithelial cell cultures, but not from either the pigmented or non-pigmented
      epithelial cells of the ciliary body cultures, but not from either the pigmented
      or non-pigmented epithelial cells of the ciliary body Cycloheximide inhibited
      secretion of Tf from the lens epithelial cells. Lenses from inflamed eyes
      contained higher levels of Tf than their contralateral controls. This is the
      first experimental demonstration that an intraocular tissue can make and secrete
      Tf. Transferrin secretion by the lens may contribute significantly to the IOF
      content of this important intraocular protein.

PMID- 7641850
TI  - Lens epithelial cell mRNA. I. Cloning and sequencing of a messenger RNA with a
      basic motif/leucine-rich domain specifically expressed in rat lens epithelial
      cells.
AB  - By methods of subtraction-hybridization of lambda ZAP cDNA libraries, prepared
      from 4-week-old rat lens epithelial cells (capsule) and lens fiber cells
      (decapsulated lens), we have isolated a specific cDNA clone whose target mRNA is
      about 600 b long. Northern blot hybridization analysis data showed that the
      target mRNA was preferentially expressed in the lens epithelial cells; it was not
      found in the retina or in non-ocular tissues. The complete sequence of the mRNA
      was obtained both by the 5' and 3' rapid amplification of cDNA ends (5'-RACE, 3'
      RACE), and by sequencing of a clone containing the full-length cDNA insert. It
      contains 599 b. with an open reading frame at nucleotide (nt) 30 (ORF30). The
      base sequence appears to represent a complete sequence of the target mRNA, with a
      poly(A) signal at nt 563-569, and a poly(A) tail at nt 582 (GenBank accession
      #U15149). In situ hybridization showed that the target mRNA was localized in the
      anterior epithelial cells, and in the elongating cells in the bow region. The
      encoded protein of 57 amino acids (aa) contains a basic and an acidic domain. It
      is rich in leucine, which is located at the basic region of the ORF at every
      fourth aa, and at the acidic region at eight aa intervals. Therefore, there is a
      periodicity in the appearance of leucine residues in the deduced primary
      sequence, as has been seen in DNA binding proteins. Search of GenBank, EMBL and
      Swiss-Prot did not yield significant homology to any of the entered sequences in
      those databanks. Our data demonstrate that we have isolated a cDNA clone
      containing novel sequences specifically expressed in lens epithelial cells.

PMID- 7641851
TI  - Migration of retinal pigment epithelium cells in vitro is regulated by protein
      kinase C.
AB  - The migration of retinal pigment epithelial (RPE) cells is an important step in
      various pathologic conditions, including subretinal neovascularization (SRN) and
      proliferative vitreoretinopathy (PVR). Therefore, elucidation of the mechanism of
      RPE migration may be useful in devising effective treatment for these disorders.
      Since protein kinase C (PKC) has been shown to regulate the migration of other
      cell types, we studied the effects of PKC agonists and antagonists on RPE
      migration. We used an in vitro wound healing model in which a small area of a
      confluent monolayer of bovine RPE cells was denuded with a razor blade. The
      cultures were subsequently incubated with agents known to stimulate [phorbol 12
      myristate 13-acetate (PMA)] or inhibit (calphostin C, staurosporine) PKC. After
      20 hr, migration was measured as the number of cells that had entered the denuded
      area. We also measured the translocation of PKC from the cytosol to the membrane
      in order to determine the activation or inhibition of PKC by PMA and calphostin C
      in the cells. The phorbol ester PMA stimulated migration by 41%, and calphostin C
      and staurosporine inhibited migration by 38% and 31%, respectively, in a medium
      supplemented with 10% serum. To determine the requirement for serum in this
      modulation, we also measured the effects of PMA and calphostin C on RPE migration
      in serum-free medium. Under these conditions, basal migration was greatly
      decreased, but PMA stimulated migration by 177% and calphostin C inhibited
      migration by 93%. Since PKC modulation is known to induce the proliferation of
      cells, we also tested the effects of these agents on growth-inhibited migration
      by pretreating the cells with the antiproliferative drug mitomycin C. We found
      that modulation of PKC under these conditions equally affected growth-inhibited
      and growth-dependent migration. Therefore, based on the increase in RPE migration
      induced by a PKC agonist, and the decrease in migration caused by PKC
      antagonists, it is suggested that PKC-mediated signal transduction plays a
      crucial role in RPE cell migration. This knowledge may be useful in devising
      effective treatments for SRN and PVR.

PMID- 7641852
TI  - Flash and pattern electroretinogram changes with optic atrophy and glaucoma.
AB  - We investigated recent reports that, contrary to common belief, glaucoma can
      affect flash as well as pattern electroretinograms. An extensive flash and
      pattern electroretinogram test protocol was used in a large sample of glaucoma
      patients and age-matched controls who were either visually normal or had other
      optic nerve diseases. All electroretinogram parameters were reduced and delayed
      in normal people > 55 years of age. The effect did not increase in later decades.
      In patients aged < or = 55 years, flash electroretinograms showed mild reductions
      and delays from optic atrophy alone. Glaucomatous ERG changes were larger and
      increased with disease severity. Pattern electroretinograms and oscillatory
      potentials were almost equally reduced in optic atrophy and all degrees of
      glaucoma. Mildly affected patients > 55 years of age had similar
      electroretinogram change to age-matched normals in most conditions. Advanced
      glaucoma patients showed similar differences from normal irrespective of age.
      This suggests that direct diagnostic application of these results to older
      patients will be difficult, that the ERG changes in glaucoma cannot be attributed
      simply to optic atrophy and that additional widespread outer retinal damage
      occurs in glaucoma.

PMID- 7641853
TI  - Protein associated with human lens 'native' membrane during aging and cataract
      formation.
AB  - Plasma membrane contains extrinsic as well as intrinsic proteins. Changes in the
      extrinsic proteins of lens membrane during human aging and cataract formation
      have not been investigated in detail. Unlike previous studies which examined lens
      membrane after being stripped of extrinsic proteins by treatment with chaotropic
      agents, we have isolated whole or 'native' lens membrane on a sucrose gradient by
      ultracentrifugation of the total water-insoluble protein. Essentially all of the
      water-insoluble protein from young to aged to cataractous human lens appeared
      membrane associated. In young lens (20-37 years old), most of the membrane banded
      at the 25/45% sucrose interface fraction. This fraction contained relatively
      little urea-soluble protein and likely represents fiber-cell plasma membrane with
      its physiologically associated extrinsic and intrinsic proteins. With aging (62
      80 years old), about one-third of the membrane, as judged by the distribution of
      cholesterol, banded at a much higher density (50/58% sucrose fraction). The
      higher density was due to a great increase in the membrane's relative protein
      content (protein/cholesterol). Although this extra protein was composed of both
      urea-insoluble and -soluble fractions, the urea-soluble protein predominated in
      all lenses. Cataractous lens differed from aged-clear lens in that much more of
      the total membrane (70-75%) had shifted to the high density and participated in
      this massive binding of cytosolic proteins. Although alpha-crystallin was the
      principal extrinsic-membrane protein in young lens, high molecular weight
      aggregate of modified (acidic) crystallins accounted for the increased extrinsic
      protein in aging. The extrinsic proteins bound to both clear-aged and cataractous
      lens membrane were aggregated. In conclusion, examination of human lens native
      membrane fractions revealed that the association of crystallins with membrane in
      both aging and cataracts was much greater than previously recognized and most of
      this increased protein was non-covalently bound to the membrane. Much more of the
      lens total membrane from cataractous than clear-aged lens was involved in this
      massive protein association and the protein bound to cataract membrane appeared
      more highly aggregated.

PMID- 7641854
TI  - Quantitation of C-terminal modification of alpha-A crystallin during aging of the
      human lens.

PMID- 7641855
TI  - [The Italian mortality map at the municipal level].
AB  - The Italian Atlas of mortality at municipality level is the result of a research
      project coordinated by the Emilia-Romagna region and supported by the Health
      Ministry. To the realisation of this project have collaborated the Institute of
      Medical Statistics of Milano and the CILEA under the supervision of Prof. Cesare
      Cislaghi. Compared to previous equivalent products, this Atlas contains a number
      of methodological and content innovations. This was a consequence of the
      development of new statistical methods and the need of achieving different aims.
      First of all, the Atlas was aimed at describing the mortality at small area
      level, which is obtained via Kernel estimates; secondly, the objective was to
      identify suspect clusters of deaths which may suggest the existence of high risk
      areas. The Mortality Atlas is formed by 31 tables, one for each of the analysed
      cause of death; each table has a circular shape of 100 hundred kilometers radius
      and contains a variable number of municipalities; each municipality may be
      present in more than one circle. The Atlas is available on magnetic support and
      for each cause of death are provided several statistical analyses and indicators
      included in different files. One of these files can be directly used to build
      high quality maps using the graphical package MAPINFO.

PMID- 7641856
TI  - [The analysis of the spatial aggregation of health events using risk surface
      density estimation methods].
AB  - Methods for the analysis of the spatial aggregation of health events has received
      growing attention under the pressure of public opinion concern and as tools for
      the identification of potential risk sources, for monitoring relevant
      geographical areas and, finally, for public health decisions. The development of
      statistical methods for the detection and localization of spatial clusters has
      mainly concerned individual data. This paper is aimed at describing one of the
      methods proposed for the identification of clusters in the case of information at
      individual level and at presenting its extension to grouped data. This method,
      the surface density estimation method using the Kernel approach, offers
      remarkable advantages in terms of simplicity of implementation and flexibility,
      this latter being an extremely important characteristic in the case of
      exploratory analyses. For exemplification purposes, the density estimation method
      has been applied to individual data concerning the spatial distribution of
      cerebral tumors in Campi Bisenzio (FI) and to the distribution of gastric cancer
      mortality in the municipalities around Arezzo and Pesaro.

PMID- 7641857
TI  - [A new approach for the automatic detection of health event clusters].
AB  - The Italian Morality Atlas at municipality level, sponsored by the Health
      Ministry and realized by the Emilia-Romagna region in collaboration with the
      Institute of Medical Statistics of Milano, is aimed at: 1) supporting and
      stimulating the local production of mortality maps and the use of geographical
      data; 2) providing a working and research tool to local health planners; 3)
      setting a routine procedure for the detection of spatial clusters. This procedure
      is organized in several steps: the definition of the spatial domain and of the
      spatial distance metrics; the choice of the effect indicator and the standard
      population; the estimate of the density risk surface via kernel methods; the
      identification of "local maxima"; the analysis of local maxima for cluster
      detection; the description of the identified clusters. The paper investigates the
      meaning and the characteristics of spatial clusters, describes the procedure for
      their identification and discusses the opportunity to use an automated approach
      for map reading.

PMID- 7641858
TI  - [A critical review of epidemiological methods for spatial analysis].
AB  - Since the 1950's a number of methods have been developed whose aims is to provide
      enhanced mapping tools, which allow the depiction of the distribution of disease,
      and thereafter, to assess risks due to environmental factors (or other spatial
      defined factors). Our review of statistical-epidemiological methodology for
      spatial analysis of diseases shall outline the distinction between global tests
      for clustering (detection of non casual distribution of events in an area) and
      cluster detection's techniques for the identification and location of abnormal
      aggregation of disease's cases. In this paper we evaluate each-one of the
      proposed methods, on general grounds, with regard to whether they meet the aims
      of the analysis and how successful they are in overcoming problems.

PMID- 7641859
TI  - [The assessment of disease risk in the proximity of a source of environmental
      pollution: a review].
AB  - An increasingly common public health problem is the perception that disease
      incidence has increased or a cluster of disease has occurred in a community. In
      most cases, a local factor (e.g. the location of a nuclear installation) is
      hypothesized to be associated with the disease. The paper presents a review of
      the main statistical methods used to assess disease risk near a putative source
      of environmental pollution. Both techniques based on counts in area units (e.g.
      administrative units) and case-control studies are considered.

PMID- 7641860
TI  - [Bayesian analysis of ecological studies].
AB  - Studying the space-time variation of risk for a given disease may give
      etiological clues and suggestions for planning further studies to investigate the
      underlying causes. When the observed events are rare, approaches based on maximum
      likelihood may lead to unstable and largely uninformative estimates of risk and
      of its time trend due to Poisson sampling variation. In this paper we propose a
      general Bayesian model for analyzing the variation of risk in space and time. We
      applied the Bayesian model to the analysis of the geographical variation of
      breast cancer mortality, to an ecological study on the correlation between lung
      cancer mortality and degree of urbanization and industrialization and to the
      analysis of the space-time variation of cumulative prevalence of Insulin
      Dependent Diabetes Mellitus (IDDM) as observed in military examinations between
      1954 and 1989.

PMID- 7641861
TI  - [Case-control studies to assess relative risk in proximity of putative sources of
      environmental pollution].
AB  - This paper discusses the analysis of the disease risk as function of distance
      from prespecified exposure sources. Instead of the usual ecological framework,
      the proposed model is based on individual data and includes the major individual
      risks factors as covariates. The risk due to environmental exposure is modelled
      using excess relative risk as effect measure, while the effect of individual risk
      factors is modelled using relative risk. A case-control design is proposed to fit
      this model and to obtain effect estimates.

PMID- 7641862
TI  - [Comparison of epidemiologic methods in a case-control study of lung cancer and
      air pollution in Trieste, Italy].
AB  - To investigate the relationship between air pollution and histologic type of lung
      cancer we conducted a case-control study among deceased men in Trieste, Italy.
      755 cases of lung cancer and 755 controls were identified through the local
      autopsy registry. Information on smoking habits, occupation and place of
      residence was obtained from the subject's next-of-kin. Air pollution at the
      residence of each subject was estimated from the average value of total
      particulate at the nearest monitoring station. Spatial models and logistic
      regression were used to evaluate the effect of residence and air pollution on LC
      after adjustment for age, smoking habits, likelihood of exposure to occupational
      carcinogens and social group. The risk of lung cancer increased with increasing
      level of air pollution for all types of lung cancer combined (P = 0.022), for
      small cell carcinoma (P = 0.016) and for large cell carcinoma (P = 0.049).
      Compared with inhabitants of the residential area, residents of the rural area
      had a relative risk (RR) of 0.6 (95% confidence interval (CI): 0.4-1.0). The RR
      was 1.5 (1.0-2.2) for residents of the center of the city and 1.4 (1.0-2.1) for
      residents of the industrial area. In the center of the city the excess risk was
      almost completely restricted to small cell carcinoma (RR = 2.0) and to large cell
      carcinoma (RR = 2.6). In the industrial area the risk was increased especially
      for adenocarcinoma (RR = 2.1). These results provide evidence that air pollution
      is a moderate risk factor for certain histologic types of lung cancer.

PMID- 7641863
TI  - [Guidelines for investigating clusters of health events].
AB  - Clusters of health events, such as chronic diseases, injuries, and birth defects,
      are often reported to health agencies. In many instances, the health agency will
      not be able to demonstrate an excess of the condition in question or establish an
      etiologic linkage to an exposure. Nevertheless, a systematic, integrated approach
      is needed for responding to reports of clusters. In addition to having
      epidemiologic and statistical expertise, health agencies should recognize the
      social dimensions of a cluster and should develop an approach for investigating
      clusters that best maintains critical community relationships and that does not
      excessively deplete resources. Health agencies should understand the potential
      legal ramifications of reported clusters, how risks are perceived by the
      community, and the influence of the media on that perception. Organizationally,
      each agency should have an internal management system to assure prompt attention
      to reports of clusters. Such a system requires the establishment of a locus of
      responsibility and control within the agency and of a process for involving
      concerned groups and citizens, such as an officially constituted advisory
      committee. Written operating procedures and dedicated resources may be of
      particular value. Although a systematic approach is vital, health agencies should
      be flexible in their method of analysis and tests of statistical significance.
      The recommended approach is a four-stage process: initial response, assessment,
      major feasibility study, and etiologic investigation. Each step provides
      opportunities for collecting data and making decisions. Although this approach
      may not always be followed sequentially, it provides a systematic plan with
      points at which the decision may be made to terminate or continue the
      investigation.

PMID- 7641864
TI  - [Letter].

PMID- 7641865
TI  - [Letter].

PMID- 7641866
TI  - Japanese earthquake victims are being exposed to high density of asbestos. We
      need protective masks desperately.

PMID- 7641867
TI  - Manual of food quality control. 14. Quality assurance in the food control
      chemical laboratory. Food and Agriculture Organization of the United Nations
      Rome.

PMID- 7641868
TI  - Manual of food quality control. 15. Imported food inspection. Food and
      Agriculture Organization of the United Nations Rome.

PMID- 7641869
TI  - Manual of food quality control. 16. Radionuclides in food. Food and Agriculture
      Organization of the United Nations.

PMID- 7641870
TI  - Fats and oils in human nutrition. Report of a joint expert consultation. Food and
      Agriculture Organization of the United Nations and the World Health Organization.

PMID- 7641871
TI  - Membrane traffic motors.
AB  - There is a wealth of data suggesting that microtubules and associated motor
      proteins play important roles in orchestrating membrane traffic within higher
      eukaryotes, with myosins and actin filaments fulfilling similar functions in
      organisms such as fungi, algae and plants. In addition, evidence is accumulating
      that both cytoskeletal systems can co-operate within one cell. Recent studies
      have highlighted how individual motor proteins can act at multiple steps in the
      membrane-traffic pathways, and in contrast, how more than one motor type may be
      involved in each transport step and in generating organelle morphology.

PMID- 7641872
TI  - The structure of the NF-kappa B p50:DNA-complex: a starting point for analyzing
      the Rel family.
AB  - The Rel family comprises a group of structurally related, eukaryotic
      transcription factors. The similarity extends over about 300 amino acid residues,
      the Rel homology region, which is responsible for DNA binding and dimerization.
      Two independently determined structures of homodimeric NF-kappa B p50 bound to
      DNA show the Rel homology regions and the DNA target sites. The protein consists
      of two beta-barrel domains connected by a short linker. Five loops per monomer
      contact the DNA. Different half-site spacings in the two structures lead to
      different relative orientations of N- and C-terminal domains.

PMID- 7641873
TI  - Transcription factor-mediated chromatin remodelling: mechanisms and models.
AB  - The association of DNA with nucleosomes in chromatin severely restricts the
      access of the regulatory factors that bring about transcription. In vivo active
      promoters are characterised by altered, almost transparent chromatin structures
      that allow the interaction of the transcriptional machinery. Recently, enzymatic
      activities have been discovered that facilitate the binding of transcription
      factors to chromatin by modifying nucleosomal structures in a process that
      requires energy. The mechanisms by which chromatin is remodelled may involve
      nucleosome movements, their transient unfolding, their partial or even complete
      disassembly. The dynamic properties of chromatin that underlie these structural
      changes are fundamental to the process of regulated gene expression.

PMID- 7641874
TI  - Mapping cells and sub-cellular organelles on 2-D gels: 'new tricks for an old
      horse'.
AB  - Nowadays, investigators in all fields are faced with the identification of
      unknown, up- or down-regulated, modified proteins that they are trying to
      identify. Two-dimensional (2-D) gel electrophoresis, with its ability to resolve
      several thousand proteins, is an extremely powerful technique. The current
      resolution and reproducibility of 2-D gel technology and the establishment of
      computer assisted 2-D gel protein databases have paved new ways for the
      identification of proteins.

PMID- 7641875
TI  - From entangled membranes to eclectic morphologies: cubic membranes as subcellular
      space organizers.
AB  - The identification of evolutionary conserved membrane morphologies whose
      architecture is governed by cubic symmetry--cubic membranes--adds a new dimension
      to cell membrane functions and, perspicuously, to their role in subcellular space
      organization. Through analysis of electron micrographs, three families of cubic
      membranes have been unequivocally identified in which one or more (parallel)
      membranes, described by periodic cubic surfaces, partition space into two or more
      independent, albeit convoluted, subspaces of membrane potential determined
      dimensions. The choice of a particular cubic symmetry is suggested to be due to
      its activity. Here the architecture and function of multiple (> or = 3) subspace
      organization in classical membrane bound organelles is addressed. As it can be
      precisely determined with cubic membranes suggests that they can be employed as a
      reference morphology.

PMID- 7641876
TI  - Intracellular lipid heterogeneity caused by topology of synthesis and specificity
      in transport. Example: sphingolipids.
AB  - The differences in lipid composition between intracellular membranes cannot be
      adequately explained by local synthesis and degradation. Especially in the case
      of sphingolipids, which are synthesized in the Golgi complex but enriched on the
      cell surface and in endocytotic organelles, there is evidence for a cellular
      machinery that preferentially shuttles these lipids in vesicles to the cell
      surface. The machinery appears to involve the formation of domains of
      sphingolipid and cholesterol in the lumenal leaflet of Golgi membranes. Several
      pieces of evidence suggest that the selective anterograde transport of plasma
      membrane proteins may be mechanistically related to the sphingolipid domains.

PMID- 7641877
TI  - From structure to function: possible biological roles of a new widespread protein
      family binding hydrophobic ligands and displaying a nucleotide binding site.
AB  - A cytosolic 21-23 kDa protein isolated from bovine brain was demonstrated to bind
      hydrophobic ligands, particularly phosphatidylethanolamine. The protein was
      encountered in numerous tissues of several species. High expression of the mRNA
      encoding the 21-23 kDa protein was found in rat testes. Immunohistochemical
      studies showed the presence of the 21-23 kDa protein in the elongated spermatids
      and epididymal fluid of rat testis and in brain oligodendrocytes of developing
      rats. As the bovine, human and rat brain 21-23 kDa proteins had only few sequence
      homologies with already know proteins, ti was concluded that they belong to a new
      protein family. In order to get additional information on the structural features
      of the 21-23 kDa protein, we built a molecular model which displayed a nucleotide
      binding site. The affinity of the bovine brain 21-23 kDa protein towards
      nucleotides as well as its association with cytosolic proteins and small GTP
      binding proteins were demonstrated. Recently, significant sequence homologies
      were found with an antigen from Onchocerca volvulus, a fruit fly odorant-binding
      protein and the yeast protein TFS1 which is a dosage-dependent suppressor of
      CDC25 mutations. A positive regulation of RAS is carried out by CDC25 product
      which facilitates the GDP/GTP exchange on RAS proteins. These results imply that
      21-23 kDa proteins function in oxidoreduction reactions and signal mechanisms
      during cell growth and maturation.

PMID- 7641878
TI  - Dystrophin and utrophin: the missing links!
AB  - There is considerable sequence homology between dystrophin and utrophin, both at
      the protein and DNA level, and consequently it was assumed that their domain
      structures and functions would be similar. As more of the detailed biochemical
      and cell biological properties of these two proteins become known, so it becomes
      clear that there are subtle if not significant differences between them. We
      review recent findings and present new hypotheses into the structural and
      functional properties of the actin-binding domain, central coiled-coil region and
      regulatory/membrane protein-binding regions of dystrophin and utrophin.

PMID- 7641879
TI  - The eighth Datta Lecture. Molecular mechanisms in synaptic vesicle recycling.
AB  - Synaptic vesicles are specialized secretory organelles which are involved in the
      fast, point-to-point signaling typical of synapses. They store and secrete non
      peptide neurotransmitters and are continuously regenerated in nerve terminals by
      exoendocytotic recycling. This recycling represents a highly specialized form of
      the recycling pathway which occurs at the surface of all cells. Several unique
      properties make synaptic vesicles a powerful experimental model for studies of
      vesicular traffic. These unique properties include their abundance in brain, the
      high specialization of nerve terminals for synaptic vesicle recycling, the
      possibility of studying their exocytosis at the level of single events by
      electrophysiology and the availability of toxins which block their recycling.
      This lecture will summarize current information of molecular mechanisms in
      synaptic vesicle recycling with emphasis on recent studies carried out in my
      laboratory on mechanisms of vesicle reformation after exocytosis.

PMID- 7641880
TI  - Genetic disorders of the red cell membranes.
AB  - The red cell membrane is comprised of a lipid bilayer studded with transmembrane
      proteins, and laminated by a protein network, the membrane skeleton, at the
      surface of the inner monolayer. The erythrocyte owes its mechanical properties to
      the membrane skeleton. Hereditary spherocytosis, hereditary elliptocytosis or
      poikilocytosis, Southeast Asian ovalocytosis are hereditary hemolytic anemias,
      due to mutations in the genes encoding ankyrin, the anion exchanger, spectrin,
      protein 4.1 or protein 4.2, which are main proteins of the membrane. Recent
      advances in the field have led to fundamental questions.

PMID- 7641881
TI  - Structure/function studies on cytoskeletal proteins in Dictyostelium amoebae as a
      paradigm.
AB  - The actin cytoskeleton in motile non-muscle cells is being regulated by a large
      number of actin-binding proteins. A deeper insight into the complex nature of the
      dynamic rearrangements of the microfilament system during cell movement requires
      an experimental system that allows the combined application of biochemical,
      biophysical, cell biological and molecular methods. Dictyostelium amoebae are
      well suited especially for a genetic approach because they are amenable to gene
      disruption, antisense and gene tagging techniques. The actin-binding proteins
      profilin, hisactophilin and protovillin are being described in this context as
      typical examples that either bind to G-actin, or anchor the actin cytoskeleton to
      the plasma membrane, or are structurally similar to vertebrate proteins but
      distinct in their functions.

PMID- 7641883
TI  - The Grb2 adaptor.
AB  - Grb2 is an 'adaptor' protein made of one SH2 and two SH3 domains. The SH3 domains
      bind to prolinerich motifs in the C-terminal part of the ras exchange factor Sos.
      Binding of the Grb2 SH2 domain to phosphotyrosine motifs on receptors, or other
      adaptor proteins such as Shc, recruits this Grb2/Sos complex at the plasma
      membrane where Sos stimulates nucleotide exchange on ras, then ras activates raf
      and leads to MAP kinase activation. The structure of Grb2, the precise motifs
      recognised by its SH2 and SH3 domains, the way Grb2 performs its function, a
      possible regulation of its association with Sos, and its ability to complex with
      other proteins in vivo, are discussed.

PMID- 7641882
TI  - Three-dimensional architecture of the skeletal muscle ryanodine receptor.
AB  - Recent advances in determining the three-dimensional architecture of the skeletal
      muscle ryanodine receptor/calcium release channel (RyR) by cryo-electron
      microscopy and three-dimensional reconstruction are discussed. The tetrameric
      receptor is characterized by a large 4-fold symmetric cytoplasmic assembly that
      consists of many domains separated by solvent-containing crevices and holes.
      Experimental evidence suggests that at least one regulatory ligand, calmodulin,
      binds to sites on the cytoplasmic assembly that are at least 10 nanometers from
      the transmembrane channel.

PMID- 7641884
TI  - Ras-effector interactions, the problem of specificity.
AB  - Ras plays the role of a molecular switch in many cellular signalling pathways.
      The Raf-kinase has been identified as the direct target molecule of Ras in
      mammalian cells. However, in recent reports other proteins have been
      characterised as putative Ras effectors which have neither a functional nor a
      structural relationship to each other. In addition it has been shown that also
      other members of the Ras family like Rap and R-Ras can interact with some of
      these proteins. To address the problem of specificity and of biological relevance
      of the interactions, they have to be carefully quantified and the cellular
      localisation of the proteins involved taken into account.

PMID- 7641885
TI  - Protein kinases--structure and function.
AB  - The solution of crystal structures from half a dozen protein kinases during the
      last four years in different laboratories has deepened our understanding of the
      catalysis and regulation of this enzyme class, and given a vigorous impetus to
      the whole field. Due to the great degree of sequence conservation among protein
      kinases the informational yield with every new structure is high, as each is a
      representative of the enzyme family in general and most often of a subclass in
      particular. This review will focus on the active site structure of cAMP-dependent
      protein kinase (cAPK) with special regard to two new crystal structures; one of
      an active protein kinase CK1*, which may represent an as yet unsolved step in the
      kinetic pathway, and the other of the insulin receptor kinase domain, the first
      structure of a tyrosine kinase.

PMID- 7641886
TI  - Regulation of the Src protein tyrosine kinase.
AB  - Members of the Src family of protein tyrosine kinases are involved in a variety
      of cellular processes, including cell growth, cell differentiation and neuronal
      signalling. N-terminal to the catalytic domain, Src family members contain a Src
      homology 2 (SH2) domain, a Src homology 3 (SH3) domain, and a unique domain, all
      capable of protein-protein interactions. Negative regulation by phosphorylation
      of a conserved tyrosine residue at the C-terminal tail of the molecules is
      characteristic of this family of enzymes. Phosphorylation of this residue causes
      the intramolecular interactions of the SH2 domain with the tail, and of the SH3
      domain with an as yet undefined region, probably within the catalytic domain.
      Enzymatically active Src family kinases, on the other hand, are phosphorylated at
      a tyrosine in the middle of the catalytic domain and phosphorylation of this
      residue is a prerequisite for high activity. Regulators of these enzymes may thus
      act by altering the phosphorylation state of the two key tyrosine residues or by
      interfering with the regulatory intramolecular interactions, either by direct
      binding or by modification of the interfaces involved.

PMID- 7641887
TI  - Characterization of a novel protein-binding module--the WW domain.
AB  - We have identified, characterized and cloned human, mouse and chicken cDNA of a
      novel protein that binds to the Src homology domain 3 (SH3) of the Yes proto
      oncogene product. We subsequently named it YAP for Yes-associated protein.
      Analysis of the YAP sequence revealed a protein module that was found in various
      structural, regulatory and signaling molecules. Because one of the prominent
      features of this sequence motif is the presence of two conserved tryptophans (W),
      we named it the WW domain. Using a functional screen of a cDNA expression
      library, we have identified two putative ligands of the WW domain of YAP which we
      named WBP-1 and WBP-2. Peptide sequence comparison between the two partial clones
      revealed a homologous proline-rich region. Binding assays and site-specific
      mutagenesis have shown that the proline-rich motif binds with relatively high
      affinity and specificity to the WW domain of YAP, with a preliminary consensus
      that is different from the SH3-binding PXXP motif. This suggests that the WW
      domain has a role in mediating protein-protein interactions via proline-rich
      regions, similar but distinct from Src homology 3 (SH3) domains. Based on this
      finding, we hypothesize that additional protein modules exist and that they could
      be isolated using proline-rich peptides as functional probes.

PMID- 7641888
TI  - Protein-mediated protein maturation in eukaryotes.
AB  - Eukaryotic cells have developed particular strategies to support the critical
      steps in protein maturation that starts in the cytosol with the birth of a
      nascent polypeptide chain, and ends when the protein has reached the appropriate
      compartment and/or has attained its mature structure. Many of the cellular
      proteins that have evolved to promote maturation processes are constitutively
      expressed members of the highly conserved heat shock protein (hsp) family, also
      known as 'molecular chaperones'. Protein-mediated processes that occur in the
      cytosol are discussed.

PMID- 7641889
TI  - Heads or tails--what determines the orientation of proteins in the membrane.
AB  - The same translocation machinery in the endoplasmic reticulum translocates either
      the N-or the C-terminal domain of signal-anchor proteins across the membranes.
      Charged residues flanking the signal sequence are important to determine which
      end is translocated, but are not sufficient to generate a uniform topology. The
      folding state of the N-terminal segment, which is to be translocated
      posttranslationally, and the length or hydrophobicity of the signal sequence are
      additional criteria to determine protein orientation in the membrane.

PMID- 7641890
TI  - SNAREs and targeted membrane fusion.
AB  - Intracellular vesicular transport involves targeting of vesicles to their correct
      destination and subsequent fusion with the target membrane. These processes
      employ unique compartment-specific proteins in combination with general
      components which act at several transport steps. This review will summarize
      recent progress made in identifying such a machinery whose assembly and activity
      is modulated by a variety of regulatory proteins.

PMID- 7641891
TI  - Role of heterotrimeric GTP binding proteins in vesicular protein transport:
      indications for both classical and alternative G protein cycles.
AB  - Heterotrimeric G proteins are involved in hormonal signal transduction across the
      plasma membrane. Recent evidence suggests that they have a role in vesicular
      protein transport as well. Biochemical probes that interfere with the classical G
      protein cycle have been applied to the field of intracellular membrane transport
      to study their mechanism of action. Evidence has been obtained that intracellular
      G proteins act both through classical and alternative G protein cycles.

PMID- 7641892
TI  - COP-coated vesicles in intracellular protein transport.
AB  - COP-coated vesicles have originally been implicated in vesicular transport
      between subcompartments of the Golgi complex in mammals in a cis to trans
      direction. More recently, a role for COP-coated vesicles in transport between the
      endoplasmic reticulum (ER) and Golgi in mammalian cells has been proposed. Under
      certain conditions COP-coats have been localized to special domains of the
      transitional ER and to the cis side of the Golgi complex. This led to the
      assumption that COP-coated vesicles are involved in export of proteins from the
      ER. In addition, new findings point to a function of COP-coated vesicles in back
      transport of proteins from the Golgi to the ER. At present it is not known
      whether COP-coated vesicles move only in one or in both directions between ER and
      Golgi.

PMID- 7641893
TI  - COPII: a membrane coat that forms endoplasmic reticulum-derived vesicles.
AB  - Vesicle budding from the endoplasmic reticulum (ER) has been reconstituted with
      washed membranes and three soluble proteins: Sec13 complex, Sec23 complex and the
      small GTPase Sar1p. The proteins that drive this cell-free vesicle budding
      reaction form an approximately 10 nm thick electron dense coat on ER-derived
      vesicles. Although the overall mechanism of membrane budding driven by various
      cytoplasmic coats appears similar, the constituents of this new membrane coat are
      molecularly distinct from the non-clathrin coat (COP) involved in intra-Golgi
      transport and the clathrin-containing coats. The new vesicle coat has been termed
      COPII.

PMID- 7641894
TI  - Redrawing compartmental boundaries in the exocytic pathway.
AB  - Compartments can be defined both morphologically as well as biochemically. The
      former relies on a direct visualisation of membrane boundaries and the latter by
      the characterisation of enzymatic functions taking place within the compartment.
      The combination of morphology and biochemistry has led to the identification of
      several compartments within the exocytic pathway, each assumed to carry out
      independent functions in a logical succession [Palade, G. (1975) Science 189, 347
      358]. However, recent findings show that resident enzymes are confined to not one
      but at least two adjacent compartments suggesting that morphological and
      biochemical definitions do not coincide. We will here discuss these findings and
      propose a model to explain how compartments are organised and maintained along
      the exocytic pathway.

PMID- 7641896
TI  - Infertility: we're not taking new patients!

PMID- 7641895
TI  - Subfertility in the era of assisted reproduction: changes and consequences.
AB  - OBJECTIVE: To review the major changes that have occurred during the last decade
      of assisted reproduction technology (ART) practice, looking at the various
      conditions that cause subfertility. DESIGN: A short review describing the
      progress that has been made during the last decade of ART practice, analyzing the
      various conditions that cause subfertility, is presented. The efficacy of ART as
      a treatment of these conditions is discussed. CONCLUSIONS: Assisted reproductive
      technology currently is used for a wide range of indications and has become an
      acceptable tool in the treatment of subfertile couples. Yet, there is an ongoing
      debate regarding the effectiveness of ART versus conventional treatment for the
      various conditions that cause subfertility. The effectiveness of IVF in terms of
      pregnancy rate (PR) was demonstrated only for patients with severe bilateral
      tubal disease and male subfertility. For couples with other causes of infertility
      the differences in PRs do not reach statistical significance, and the efficacy of
      IVF has not been demonstrated clearly to date. Moreover, much of the discussion
      about management of subfertility has centered on costs of ART and the cost
      benefit of ART versus conventional therapy for subfertility. It has been shown
      that, in women with unexplained infertility, menotropin treatment is as
      successful, less expensive, and carries a smaller risk than the surgical approach
      used in ART. However, the exact role of ART in the management of polycystic
      ovarian syndrome, immunological infertility, and endometriosis still is to be
      determined. Yet, as embryo implantation after ART still is considerably lower
      than that of fertile couples who conceive naturally, we expect that the next
      major thrust improving the effectiveness of ART will occur after future
      elucidation of factors influencing embryonic implantation.

PMID- 7641898
TI  - Endosalpingiosis found at laparoscopy for chronic pelvic pain.
AB  - OBJECTIVE: To assess a correlation between endosalpingiosis and pelvic pain.
      DESIGN: A retrospective analysis of every patient undergoing laparoscopy for
      chronic pelvic pain at Yale-New Haven Hospital by one surgeon from August 1992
      through October 1993 was performed, focusing on those cases with
      endosalpingiosis. RESULTS: Of 51 laparoscopies performed for chronic pelvic pain,
      37 demonstrated visual evidence of implants and pathology specimens were read as
      either endometriosis or endosalpingiosis in 23 cases. Of those 23 cases, 6
      demonstrated endosalpingiosis, and 4 of those 6 demonstrated both
      endosalpingiosis and endometriosis. In all six cases endosalpingiosis was found
      in locations consistent with the patients' pelvic pain symptoms, and all six
      patients experienced relief from their pain symptoms after surgery. CONCLUSIONS:
      Endosalpingiosis may be found in association with chronic pelvic pain. The pelvic
      distribution of endosalpingiosis in patients with chronic pain is consistent with
      that generally found in endometriosis.

PMID- 7641897
TI  - Gonadotropin-releasing hormone analogue (goserelin) plus hormone replacement
      therapy for the treatment of endometriosis: a randomized controlled trial.
AB  - OBJECTIVE: To determine whether treatment of endometriosis with a GnRH analogue
      (GnRH-a; goserelin) combined with continuous estrogen and progestogen hormone
      replacement therapy (HRT) would prevent the hypoestrogenic effects, including
      loss of bone density, while maintaining efficacy for treatment of endometriosis.
      DESIGN: Randomized controlled trial. PATIENTS: Fifty premenopausal women with
      laparoscopically diagnosed endometriosis (revised American Fertility Score for
      endometriosis implants equal to four or greater) and significant symptoms of
      dysmenorrhoea, dyspareunia, and other pelvic pain. INTERVENTION: Patients were
      randomized to receive either goserelin alone, 3.6 mg SC depot every 4 weeks for
      24 weeks, or goserelin, 3.6 mg SC depot every 4 weeks for 24 weeks, plus HRT (25
      micrograms transdermal 17 beta E2 daily and 5 mg medroxyprogesterone acetate
      orally daily) for 20 weeks commencing with the second goserelin injection.
      RESULTS: There was a significant reduction in the extent of pelvic endometriosis
      in both groups, with no difference between the groups. Both groups experienced an
      improvement in symptoms and signs, again with no difference between groups.
      Hypoestrogenic side effects of hot flushes and loss of libido were significantly
      less in the group that received HRT. The amount of bone mineral density loss was
      significantly less in the HRT group at the lumbar spine, although it was not
      prevented completely. CONCLUSION: The addition of HRT to GnRH-a for the treatment
      of endometriosis did not reduce the efficacy of treatment, and adverse
      hypoestrogenic effects were decreased, although not abolished.

PMID- 7641899
TI  - The accuracy of hysterosalpingography in the diagnosis of tubal pathology: a meta
      analysis.
AB  - OBJECTIVE: To assess the value of hysterosalpingography (HSG) in diagnosing tubal
      patency and peritubal adhesions using laparoscopy with chromopertubation as the
      gold standard. DESIGN: Meta-analysis of 20 studies comparing HSG and laparoscopy
      for tubal patency and peritubal adhesions. PATIENTS: Four thousand one hundred
      seventy-nine patients with infertility in 20 studies. INTERVENTION:
      Hysterosalpingography and diagnostic laparoscopy as part of infertility workup.
      MAIN OUTCOME MEASURE: Tubal patency and peritubal adhesions. RESULTS: For tubal
      patency the reported sensitivity and specificity differed between studies. In a
      subset of studies that evaluated HSG and laparoscopy independently, a point
      estimate of 0.65 for sensitivity and 0.83 for specificity was calculated. For
      peritubal adhesions a summary receiver operating characteristic curve could be
      estimated. CONCLUSIONS: Although HSG is of limited use for detecting tubal
      patency because of its low sensitivity, its high specificity makes it a useful
      test for ruling in tubal obstruction. For the evaluation of peritubal adhesions
      HSG is not reliable.

PMID- 7641900
TI  - Effects of aging on menstrual cycle hormones and endometrial maturation.
AB  - OBJECTIVE: To investigate changes in menstrual cycle hormones and endometrial
      maturation that may contribute to the decline in fertility with aging. DESIGN:
      Prospective controlled clinical study. SETTING: Normal human volunteers in an
      academic research institution. SUBJECTS: Women with regular menstrual cycles.
      INTERVENTIONS: Thirty-two women, aged 20 to 30 or 40 to 50 years, had daily blood
      drawing starting on cycle day 6 to 10 and continuing until 2 days after the onset
      of next menses. In addition, 60 women, aged 20 to 30 or 40 to 50 years, had a
      total of 93 endometrial biopsies performed on day 7 to 9 after the LH surge. MAIN
      OUTCOME MEASURES: Serum LH, FSH, E2, inhibin, P, and placental protein 14 (PP14)
      levels and histologic maturation of the endometrium. RESULTS: Serum FSH levels
      were increased whereas inhibin concentrations were reduced in the luteal
      follicular transition of women > 40 years. No other hormonal changes were seen in
      this population, including P and PP14 secretion. Disruption of endometrial
      maturation occurred at a similar frequency in both age groups. CONCLUSIONS:
      Follicular recruitment, but not luteal function or endometrial maturation, is
      disturbed in cycling women > 40 years and may contribute to the decline in
      fertility with aging.

PMID- 7641901
TI  - Color flow pulsed Doppler ultrasound in diagnosing luteal phase defect.
AB  - OBJECTIVE: To determine whether color flow pulsed Doppler analysis of corpus
      luteum blood flow in normal cycles differs from cycles with a luteal phase
      defect. DESIGN: A prospective study of natural ovarian cycles. SETTING: The
      University of Vermont Reproductive Endocrinology and Infertility Service.
      PATIENTS: Ten women with regular menstrual cycles and at risk for luteal phase
      defect (LPD) four with unexplained infertility, two with recurrent abortion, and
      four with age > 35 years. INTERVENTIONS: All women were examined by transvaginal
      color flow pulsed Doppler during the early follicular, late follicular, early
      luteal, midluteal, and late luteal phase of the menstrual cycle. Venous blood for
      P concentration was drawn on each day of Doppler exam. Urine testing for LH surge
      and endometrial biopsy during the late luteal phase were performed on each
      patient. MAIN OUTCOME MEASURES: Lowest resistance index associated with the
      highest amplitude signal from intraovarian vessels of each ovary, dated
      endometrial biopsies, serum P. RESULTS: Mean resistance indexes in LPD patients
      (n = 3) were significantly higher compared with normal women (n = 6) throughout
      the follicular and luteal phases. One patient remained anovulatory and was
      excluded from statistical analysis. Although systolic and diastolic velocities
      generally were observed to be lower in LPD patients compared with normal women,
      these differences were not statistically significant. High correlations were
      observed between P and resistance index within each luteal time point, achieving
      its highest value during the midluteal phase. CONCLUSIONS: This initial study
      provides evidence that color flow pulsed Doppler analysis of blood flow impedance
      to the corpus luteum may aid in assessing luteal phase adequacy.

PMID- 7641902
TI  - A new system for fallopian tube sperm perfusion leads to pregnancy rates twice as
      high as standard intrauterine insemination.
AB  - OBJECTIVE: To evaluate the relative efficacy of a new system for fallopian tube
      sperm perfusion in comparison with standard IUI in controlled ovarian
      hyperstimulation (COH) cycles. DESIGN: Prospective randomized trial. SETTING:
      Ovulation induction program of a tertiary outpatient care center, Hopital Antoine
      Beclere, Clamart, France. PATIENTS: We studied 74 infertile women aged 20 to 38
      years undergoing 100 cycles of COH from December 1993 to May 1994 only excluding
      cases of age > 38 years, obstructed or severely damaged fallopian tubes, E2
      levels per mature follicle < 250 pg/mL (conversion factor to SI unit, 3.671) on
      the day of hCG administration, spontaneous LH surge, and cases of marked sperm
      abnormalities. INTERVENTIONS: Controlled ovarian hyperstimulation was achieved
      using three types of ovarian stimulation protocols: clomiphene citrate (CC) and
      hMG (n = 35). hMG alone (n = 35) or GnRH agonist and FSH and hMG (n = 30). Thirty
      six hours after hCG administration, patients were assigned randomly to either IUI
      (group A, n = 50) or fallopian tube sperm perfusion (group B, n = 50).
      Intrauterine insemination was performed with 0.2 mL of sperm suspension according
      to a standard technique. Fallopian tube sperm perfusion was performed using a
      simple and reliable system that ensures a good cervical seal and allows to a
      pressurized injection of 4 mL of sperm suspension. MAIN OUTCOME MEASURES:
      Feasibility of the fallopian tube sperm perfusion method, clinical pregnancy
      (presence of gestational sac with heart beats at 6 weeks of amenorrhea), and
      ongoing pregnancy rates (PRs) (> 12 weeks of amenorrhea), incidence of
      complications (multiple pregnancies and ovarian hyperstimulation syndrome
      [OHSS]). RESULTS: Overall, the new fallopian tube sperm perfusion system was
      simple to handle and well tolerated by patients. In group A, we observed 10
      clinical pregnancies (20% per cycle) of which 7 were ongoing (14%). In group B,
      20 clinical pregnancies (40% per cycle) of which 17 ongoing pregnancies (34%)
      were obtained. These differences were statistically significant. The prevalence
      of twin and three or more sac pregnancies was similar in the two groups (3/10 and
      0/10, respectively, in group A, and 5/20 and 2/20, respectively, in group B). No
      case of moderate or severe OHSS was observed in this series. CONCLUSIONS: Our
      results indicate that the new system for fallopian tube sperm perfusion is not
      only simple and reliable but also may lead to PRs twice as high as standard IUI
      in COH cycles.

PMID- 7641903
TI  - Flutamide in the treatment of hirsutism: long-term clinical effects, endocrine
      changes, and androgen receptor behavior.
AB  - OBJECTIVE: To investigate the long-term effects of treatment with low doses of
      flutamide on clinical and hormonal parameters, as well as on the androgen
      receptor status, in hirsute women. DESIGN: Eighteen hirsute patients with regular
      menses were studied basally and during treatment with 125 mg flutamide, three
      times per day for 12 months. Barrier or intrauterine contraception was used
      during the study in sexually active women. Safety parameters were assessed
      throughout the study. Hirsutism, graded by the modified Ferriman-Gallwey score,
      and hormonal parameters were evaluated basally and at 4-month intervals during
      treatment. Gonadotropin-releasing hormone and ACTH stimulation tests were
      performed before and after 3 to 4 months of therapy. In addition, the
      concentration of androgen receptors in mononuclear leukocytes was measured, in
      both the follicular and luteal phases of the menstrual cycle, basally and after 4
      months of flutamide treatment. RESULTS: Flutamide was well tolerated in all
      women, with the noticeable exception of one patient who presented increased serum
      transaminase after 8 months of therapy. Hirsutism markedly improved in all women
      during the treatment (Ferriman-Gallwey score after 1 year: 4.1 +/- 0.5 versus
      14.1 +/- 0.9). A reduction of serum androgens was found, whereas no change was
      observed in either basal or GnRH-stimulated gonadotropins or in the cortisol and
      17 alpha-hydroxyprogesterone response to ACTH. Cycles remained ovulatory. Before
      treatment, the number of androgen receptors was higher in the luteal than in the
      follicular phase. This rhythmic differentiation disappeared after the patients
      had been given the antiandrogen drug. CONCLUSIONS: Flutamide is effective in the
      treatment of hirsutism but requires constant surveillance of liver function.
      Androgen receptor blockade might be potentiated by a reduction of serum
      androgens. Flutamide affects androgen receptor behavior during the menstrual
      cycle. The meaning of this finding remains to be elucidated.

PMID- 7641904
TI  - The follicle-stimulating hormone receptor gene is polymorphic in premature
      ovarian failure and normal controls.
AB  - OBJECTIVE: To examine the FSH receptor gene for detectable abnormalities in women
      with premature ovarian failure. DESIGN: Study of genomic DNA from controls and
      from patients with 46,XX premature ovarian failure (POF). SETTING: Clinics and
      laboratories of university gynecology and obstetrics departments. PATIENTS:
      Twenty-one women with 46,XX POF and 40 normal fertile controls. INTERVENTIONS:
      Deoxyribonucleic acid was analyzed in patients and controls by Southern blot
      analysis, polymerase chain reaction (PCR), and denaturing gradient gel
      electrophoresis. Southern blots were hybridized with the FSH receptor
      complementary DNA and other smaller DNA probes. Exons 1, 5 to 6, and 10 were
      amplified by PCR and electrophoresed on agarose gels. Polymerase chain reaction
      products from exons 1 and 10 were electrophoresed on denaturing gradient gels.
      MAIN OUTCOME MEASURES: Fragments obtained by Southern blot analysis and PCR were
      compared in patients and controls. Polymerase chain reaction fragments
      electrophoresed on denaturing gels also were compared in patients and controls.
      CONCLUSIONS: No FSH receptor gene deletions or other mutations were identified in
      women with POF. Southern blots containing PstI- and HindIII-digested DNA revealed
      restriction fragment length polymorphisms in both patients and controls.
      Denaturing gradient gel electrophoresis analysis of PCR fragments of exon 10 also
      demonstrated DNA sequence polymorphisms in both patients and controls. Follicle
      stimulating hormone receptor gene deletions are not common in women with POF,
      although the gene is polymorphic. We cannot exclude point mutations in other
      regions of the FSH receptor gene in some patients with POF.

PMID- 7641906
TI  - Ovarian senescence and its significance on uterine and ovarian perfusion.
AB  - OBJECTIVE: To measure the flow velocity of the ovarian, uterine, radial, and
      spiral arteries in different age groups. DESIGN: Serial measurements throughout
      the menstrual cycle in normal cycling women with documented fertility were
      compared with those in postmenopausal patients with and without hormone
      replacement therapy (HRT). SETTING: Department of Obstetrics and Gynecology,
      University of Zagreb, Sveti Duh Hospital, Zagreb, Croatia. PATIENTS: Two hundred
      fifty patients were analyzed: 120 healthy fertile women, 85 postmenopausal
      patients, and 45 postmenopausal patients receiving HRT. INTERVENTIONS: All
      patients were examined by transvaginal color and pulsed Doppler. MAIN OUTCOME
      MEASURE: Changes in the resistance index of flow velocity waveforms of the
      ovarian, uterine, radial, and spiral arteries. RESULTS: Ovarian artery Doppler
      measurements in postmenopausal patients showed a significant difference when
      compared with the ovarian artery on the side containing dominant follicle or
      corpus luteum in healthy fertile group. Uterine and radial artery flow velocity
      analyses demonstrated significant positive correlations between the resistance
      index and years of menopause. In patients receiving HRT, a lowering effect
      occurred in the resistance index of the main uterine artery and its
      intramyometrial branches. Visualization of clear Doppler signals from the spiral
      arteries was possible in 30% of women who were menopausal for < 5 years.
      Increased vascular impedance was the typical finding in this vessel for this
      group of patients. The addition of HRT resulted in higher visualization rates of
      the spiral arteries and lowered resistance index values. CONCLUSIONS: There are
      changes in the flow velocity patterns of the ovarian, uterine, radial, and spiral
      arteries with age. The fact that the uterine artery resistance index does not
      change significantly in the first postmenopausal years strongly supports the
      thesis that the aging process initially affects the uterus less than the ovary.
      Furthermore, the uterine environment can be manipulated more easily during the
      menopausal years by proper hormonal stimulation.

PMID- 7641905
TI  - The effect of medrogestone on plasma lipids and lipoproteins in postmenopausal
      women using conjugated estrogens: an open randomized comparative study.
AB  - OBJECTIVE: To test the hypothesis that the progestogen medrogestone has no effect
      on changes in lipoprotein metabolism evoked by continuous estrogen replacement
      therapy, paying special attention to high-density lipoproteins (HDL). DESIGN:
      Open multicenter randomized comparative trial. PATIENTS: Postmenopausal
      hysterectomized women aged 49 to 64 years. INTERVENTION: Continuous oral
      treatment with 0.625 mg daily of conjugated estrogens (CE) alone (n = 55) or CE
      plus 5 mg of the progestogen medrogestone orally during the last 12 days of each
      28-day cycle (n = 59). MAIN OUTCOME MEASURES: At baseline and at cycles 3, 6, and
      13 we measured the plasma levels of apolipoprotein (Apo) A1, cholesterol in total
      HDL and in its subfractions HDL2 and HDL3, using density gradient
      ultracentrifugation. RESULTS: High-density lipoprotein cholesterol increased from
      baseline at all assessments in both treatment groups, being significantly greater
      in the CE group (+15% at cycle 13) than in the CE and medrogestone group (+8%).
      However, HDL2-cholesterol increased in both treatment groups, but with no
      significant difference between the two groups. High-density lipoprotein 3
      cholesterol increased only in the CE group (+7% at cycle 13); there was no
      significant change in HDL3-cholesterol in the CE and medrogestone group. Low
      density lipoprotein (LDL) cholesterol decreased from baseline at all assessments
      in both treatment groups (-6% and -9%, respectively, at cycle 13). The change in
      very low-density (VLDL) lipoprotein cholesterol was not significant in either of
      the two groups. Medrogestone had no significant effects on the estrogen-induced
      increases in apo A-1 and triglycerides nor on the decreases in ApoB and LDL
      cholesterol. Neither hormone significantly affected VLDL-cholesterol or Lp(a)
      levels. CONCLUSION: Medrogestone did not eliminate the increase in plasma HDL
      levels evoked by CE.

PMID- 7641907
TI  - An estimate of the cost of in vitro fertilization services in the United States
      in 1995.
AB  - OBJECTIVE: To estimate the cost of adding IVF treatment to a standard health care
      benefits package. In vitro fertilization cost is defined as the average charge
      for a single cycle of treatment in an existing IVF program. DESIGN: Cost
      analysis. SETTING: Two hundred sixty IVF centers active in the United States in
      1993. MAIN OUTCOME MEASURES: In vitro fertilization utilization and outcomes for
      1993 were estimated from data in an existing registry. In vitro fertilization
      charges were determined from a 1993 survey of IVF clinics. The resulting
      expenditures for benefits and premiums were projected to 1995 together with the
      additional cost if utilization were to increase by 300% or 500%. RESULTS: In the
      United States in 1993 there were 31,718 IVF cycles for which the average charge
      was $6,233, leading to a total expenditure of approximately $197.70 million for
      IVF services in 1993. The projected cost of adding IVF services to a typical
      employer health plan in 1995 would be $2.79 per annum and the premium would be
      $3.14. Benefits and premium costs for a 300% utilization increase were $8.37 and
      $9.41, respectively, and for a 500% increase, $13.95 and $15.69, respectively.
      CONCLUSIONS: The cost of IVF services would be a minute fraction of the annual
      cost of a typical family benefits program ($3,393). Savings from reduced
      utilization of alternative treatments would offset a portion of this increase.
      Increases in utilization rates should be controlled by clinical criteria.

PMID- 7641908
TI  - Second time around: a study of patients seeking second assisted reproduction
      pregnancies.
AB  - OBJECTIVE: To investigate the outcomes of subsequent cycles of IVF-ET, GIFT, and
      frozen ET in patients who have already achieved at least one assisted
      reproductive technology (ART) pregnancy. DESIGN: Retrospective cohort. SETTING:
      Private infertility clinic, Brisbane, Queensland, Australia. PATIENTS: From 1985
      to 1992, 4,680 patients underwent 13,106 ART oocyte retrieval cycles. One
      thousand nine hundred twenty-two patients achieved a pregnancy, and 784 returned
      for a second pregnancy. These 784 return patients were divided into two
      subgroups: group A (288 patients) took home at least one baby from their first
      pregnancy; group B (496 patients) had an unsuccessful first pregnancy. MAIN
      OUTCOME MEASURES: Pregnancy rate (PR), cumulative PR, pregnancy outcome. RESULTS:
      Patients returning for second and third ART pregnancies had an increased chance
      of success. Pregnancy rates increased from 31.0% per transfer for patients
      attempting their first GIFT pregnancy, to 34.7% and 42.7% per transfer for
      patients attempting their second and third GIFT pregnancy. Cumulative PRs
      increased with subsequent pregnancy attempts. Groups A and B did not differ in
      PR, age, or indication of infertility but had significantly different live birth
      rates. The pregnancy outcomes of frozen ETs depended on the outcomes of the
      original cycle from which the embryos were derived. CONCLUSIONS: This study has
      important implications for the counseling of patients returning for subsequent
      ART pregnancies.

PMID- 7641909
TI  - Minimal monitoring of ovarian hyperstimulation: a useful simplification of the
      clinical phase of in vitro fertilization treatment.
AB  - OBJECTIVE: To investigate the feasibility of IVF treatment with minimal
      monitoring during ovarian hyperstimulation. DESIGN: Retrospective analysis and
      prospective study with real-time control group. SETTING: Transport IVF program
      with transport clinic and satellite clinics. PATIENTS: One hundred consecutive
      IVF cycles monitored at a transport clinic and 100 concurrent consecutive cycles
      monitored at satellite clinics, using the same stimulation-monitoring protocol
      and resulting in oocyte aspiration, are compared retrospectively for the number
      of ultrasound (US) measurements carried out during monitoring and for results of
      IVF treatment. No patient selection took place. After introduction of a minimal
      monitoring protocol at a transport clinic, a prospective study was started
      comparing 100 minimal monitoring cycles at a transport clinic with 100 concurrent
      conventional monitoring cycles at satellite clinics, all resulting in oocyte
      aspiration. Patients entered the retrospective or prospective study only once. In
      all cases the same laboratory facility was used. Monitoring of ovarian
      hyperstimulation was done with US measurements only. Cycles were canceled for
      impending ovarian hyperstimulation syndrome (OHSS) when > 35 follicles were seen
      to develop during hyperstimulation. RESULTS: Retrospective analysis shows no
      difference for the average number of US measurements at transport and satellite
      clinics (2.8 +/- 0.9 and 3.0 +/- 1.0; mean +/- SD). No differences were found in
      the number of ongoing pregnancies obtained in the two groups: 22 and 18,
      respectively. One case of severe OHSS occurred in the satellite clinic group.
      Introduction of minimal monitoring at the transport clinic gives a significant
      reduction of the average number of US measurements at the transport clinic
      compared with satellite clinics, where conventional monitoring continued to be
      used (1.5 +/- 0.8 versus 2.8 +/- 0.9). Ongoing pregnancies at transport and
      satellite clinics numbered 33 and 26, respectively. In both groups one patient
      developed severe OHSS. Sixty-two percent of cycles at the transport clinic were
      monitored with one US measurement only. No cancellations for impending OHSS
      occurred during the study period. CONCLUSION: A large group of patients need only
      one US measurement during monitoring of ovarian hyperstimulation. Minimal
      monitoring gives a useful further simplification of the clinical phase of IVF
      treatment, without adverse effects on treatment outcome and incidence of OHSS.

PMID- 7641910
TI  - Type of stimulation protocol affects oocyte maturity, fertilization rate, and
      cleavage rate after intracytoplasmic sperm injection.
AB  - OBJECTIVE: To compare oocyte maturity, fertilization rate and cleavage rate after
      a short and long GnRH agonist (GnRH-a) stimulation protocol and intracytoplasmic
      sperm injection (ICSI). DESIGN: Retrospective study of 34 sequential ICSI cycles
      stimulated with a short or long GnRH-a protocol. SETTING: A university-based
      tertiary care center for assisted reproductive treatment. RESULTS: Significantly
      more oocytes were mature (metaphase II) after a long GnRH-a protocol then after a
      short GnRH-a protocol (25.6% and 80.8%, respectively). The long protocol resulted
      in more cleaving embryos (36/152 versus 9/132) and more cycles of ET (12/17
      versus 5/17) than the short group. CONCLUSION: A greater percentage of mature
      oocytes results from ovarian stimulation with a long GnRH-a protocol than a short
      GnRH-a protocol. Maturity could be assessed accurately after cumulus stripping
      that is required before ICSI. Fertilization rate and cleavage rate with ICSI was
      superior after a long GnRH-a stimulation protocol for superovulation.

PMID- 7641912
TI  - Baseline cyst formation after luteal phase gonadotropin-releasing hormone agonist
      administration is linked to poor in vitro fertilization outcome.
AB  - OBJECTIVE: To investigate the prognostic significance of baseline ovarian cysts
      after luteal phase GnRH agonist (GnRH-a) administration for IVF-ET. DESIGN: All
      nondonor IVF-ET cycles in one program in which luteal phase GnRH-a was
      administered between July 1993 and January 1994 were assessed for the formation
      of baseline ovarian cysts defined as a mean diameter > or = 15 mm. Outcome data
      from the IVF cycles were compared between patients with and without baseline
      ovarian cysts. RESULTS: Of 78 IVF cycles, baseline cysts > or = 15 mm were noted
      in 26 cycles. Cycles in which cysts were formed were associated with
      significantly older patients with significantly higher baseline FSH values.
      Cycles in which cysts were present demonstrated fewer follicles, retrieved
      oocytes, and embryos. Cyst cycles also demonstrated a lower peak E2 level,
      implantation rate, and clinical pregnancy rate (PR) per initiated cycle (7.7%
      versus 32.7%). Cyst cycles also demonstrated a higher cancellation rate. Logistic
      regression modeling, accounting for age, confirmed significantly lower clinical
      PRs in cycles with a baseline cyst. CONCLUSIONS: Baseline cyst formation after
      luteal phase GnRH-a administration is both a marker for poor responders and a
      reliable predictor of poor stimulation and low PRs in a given IVF-ET cycle.

PMID- 7641911
TI  - Polycystic ovary syndrome patients as oocyte donors: the effect of ovarian
      stimulation protocol on the implantation rate of the recipient.
AB  - OBJECTIVE: To evaluate the outcome of oocytes donated by women with polycystic
      ovarian syndrome (PCOS) compared with oocytes donated by women with mechanical
      infertility. DESIGN: A retrospective study. PATIENTS: The outcome of 159 oocyte
      donation cycles with oocyte donated by PCOS patients were compared with 69 oocyte
      donation cycles with oocytes donated by patients with mechanical infertility. We
      compared the stimulation protocols in the donors to assess if the combination of
      GnRH analogue (GnRH-a), FSH, and hMG has an advantage over FSH and hMG alone with
      respect to their effect on fertilization and implantation rates in oocyte
      donation cycles. RESULTS: When treated with GnRH-a, pregnancy rates in PCOS and
      mechanical infertility donors were higher than those treated with FSH and hMG
      alone. The comparison between PCOS and mechanical factor oocyte recipients
      revealed no significant difference in the pregnancy and abortion rates, but the
      oocytes of patients with PCOS that were exposed to GnRH-a had a significantly
      higher implantation rate than those not exposed to GnRH-a. CONCLUSIONS: Oocytes
      obtained from PCOS patients had a fertilization potential equal to oocytes
      obtained from mechanical infertility donors. Furthermore, because the oocytes of
      patients with PCOS exposed to GnRH-a had a significantly higher implantation
      rate, a detrimental role of high LH on oocyte quality seems probable. However,
      because PCOS has a high familial prevalence, some reservations may arise due to a
      possible propagation of the problem in the next generation of oocyte donation
      programs.

PMID- 7641913
TI  - Luteal phase consequences of low-dose gonadotropin-releasing hormone agonist
      therapy in nonluteal-supported in vitro fertilization cycles.
AB  - OBJECTIVE: To determine the follicular and luteal phase impact of low-dose GnRH
      agonist (GnRH-a) treatment during follicular stimulation for IVF. DESIGN: A
      randomized prospective study compared patients receiving low-dose GnRH-a and hMG
      therapy to clomiphene citrate (CC) and hMG cycles. SETTING: Patients were treated
      through a university-based IVF-ET program. PATIENTS: Thirty-six patients
      underwent follicular stimulation with low-dose GnRH-a and hMG and were compared
      with 34 patients undergoing ovulation induction with CC and hMG. RESULTS:
      Significantly shorter luteal phase length occurred with GnRH-a and hMG therapy;
      however, there was no statistically significant difference in luteal P levels.
      Follicular parameters were the same (peak E2, number of follicles, and number of
      oocytes), suggesting that folliculogenesis was not altered. There were no
      statistical differences in pregnancy rates. CONCLUSIONS: Sustained low-dose GnRH
      a therapy during follicular stimulation does not have a clinical effect on luteal
      function.

PMID- 7641914
TI  - Mitochondrial deoxyribonucleic acid deletions in oocytes and reproductive aging
      in women.
AB  - OBJECTIVE: To determine whether oocytes from women harbor deletions in
      mitochondrial DNA (mtDNA) and whether deleted mtDNA is more common in oocytes
      from older women than oocytes from younger women. DESIGN: A polymerase chain
      reaction (PCR)-based strategy, which depends on deletions approximating otherwise
      widely separated primers to demonstrate mtDNA deletions in individual oocytes,
      was used. SETTING: Yale In Vitro Fertilization Clinic and Laboratory at Yale
      University School of Medicine. MAIN OUTCOME MEASURES: Primers flanked a region of
      the mitochondrial genome in which long direct repeated sequence predispose to
      deletions. The primers identified the 0.5-kb "common" deletion. Deleted mtDNA was
      represented by a 0.5-kb band when primers separated by 5 kb were used. Control
      reactions used primers that amplify mtDNA outside the deletion hotspot. Positive
      controls included brain and/or muscle from aged individuals, and negative
      controls included fetal tissue and DNA-free blanks. Nested primers confirmed the
      specificity of the deleted product. RESULTS: Unfertilized oocytes, muscle, and
      brain tissue contained PCR products consistent with deleted mtDNA. Fetal tissue
      lacked the mtDNA deletion product. Deleted mtDNA was detected in single oocytes.
      Oocytes from older women were more likely to contain deleted mtDNA than oocytes
      from younger women. CONCLUSION: Deleted mtDNA in unfertilized oocytes may serve
      as a marker of oocyte senescence.

PMID- 7641915
TI  - Ovarian 11 beta-hydroxysteroid dehydrogenase activity is inversely related to the
      outcome of in vitro fertilization-embryo transfer treatment cycles.
AB  - OBJECTIVES: To determine the relationship of ovarian 11 beta-hydroxysteroid
      dehydrogenase (11 beta-HSD) activity to the outcome of IVF-ET and to establish
      whether 11 beta-HSD activities vary for a given patient between consecutive
      treatment cycles. DESIGN: Retrospective correlation analysis. SETTING: Patients
      were treated and ovarian 11 beta-HSD activities were measured at independent
      fertility and biochemistry departments, respectively. PATIENTS: Random series of
      137 women undergoing a total of 172 treatment cycles for IVF-ET. INTERVENTIONS:
      Subcutaneous buserelin acetate plus IM hMG and hCG for controlled ovarian
      hyperstimulation; blood samples were collected for plasma LH and steroid
      determinations. MAIN OUTCOME MEASURES: Presence or absence of detectable ovarian
      11 beta-HSD activity, oocyte fertilization rates, and the identification of
      clinical pregnancies. RESULTS: None of the 101 cycles associated with 11 beta-HSD
      positive granulosa-lutein cells resulted in clinical pregnancies, whereas the
      pregnancy rate for the 71 patients with undetectable ovarian 11 beta-HSD activity
      was 63.4% per cycle. The incidence of total fertilization failure was lower and
      the median oocyte fertilization rate was higher in cycles characterized by 11
      beta-HSD-negative cells. Plasma concentrations of LH and E2 were higher in cycles
      yielding 11 beta-HSD-negative cells, whereas plasma P, patient age, and the
      number of oocytes retrieved did not relate to ovarian 11 beta-HSD activity. For
      the 35 patients studied in repeat cycles, ovarian 11 beta-HSD activities did not
      relate to those in the initial cycles. CONCLUSIONS: Ovarian 11 beta-HSD activity
      is associated with failure to conceive by IVF-ET. For a given patient, ovarian 11
      beta-HSD activity varies between consecutive treatment cycles. Hence, ovarian 11
      beta-HSD activities may predict the outcome of this assisted reproduction
      protocol independently in each treatment cycle.

PMID- 7641917
TI  - Microdissection of mouse and human zona pellucida using a 1.48-microns diode
      laser beam: efficacy and safety of the procedure.
AB  - OBJECTIVE: To investigate the efficacy and safety of a small and affordable 1.48
      microns continuous wave diode laser for zona pellucida (ZP) microdissection.
      DESIGN: Mouse and human oocytes and zygotes were submitted to ZP drilling. The
      hole characteristics and possible laser-induced structural alterations of the
      neighboring cytoplasm were investigated with scanning and transmission electron
      microscopy. The safety of the procedure was checked on control and drilled
      zygotes by determining their ability to develop in vitro and in vivo. SETTING:
      Collaborative study between three Swiss academic centers. INTERVENTIONS: The
      collimated diode laser beam was delivered through a 45x objective of an inverted
      microscope and focused through the culture dish and culture medium in 1- to 3
      microns spots. MAIN OUTCOME MEASURE: Safety assessment of the laser drilling
      procedure. RESULTS: The 1.48-microns radiation achieves a rapid, precise, and
      easily controlled lysis of the ZP without any micromanipulative handling of the
      eggs. Different shapes of holes can be produced by varying the laser beam
      intersection site on the ZP, laser power, and irradiation time. The energy needed
      to drill holes of a given diameter is greater for zygotes than for oocytes.
      Safety of the drilling procedure is confirmed by the lack of damage at the
      ultrastructural and biologic levels. CONCLUSIONS: The low-cost 1.48-microns diode
      laser allows an easy, objective-driven, nontouch microdissection of the ZP. The
      procedure is safe, as drilled embryos give rise to normal and fertile offspring.

PMID- 7641916
TI  - Cadmium accumulation in follicular fluid of women in in vitro fertilization
      embryo transfer is higher in smokers.
AB  - OBJECTIVE: To assess cadmium, a heavy metal in cigarette tobacco, in follicular
      fluid (FF) of women in IVF-ET, who smoke. DESIGN: Controlled clinical study.
      SETTING: Infertile patients in a hospital IVF-ET program. PATIENTS: Fifty-one
      women selected in groups according to smoking habits: nonsmokers (n = 10),
      passive smokers (n = 17), light smokers (< 15 cigarettes per day, n = 19), and
      heavy smokers (> or = 15 cigarettes per day, n = 5). INTERVENTIONS: Ovarian
      hyperstimulation with GnRH agonist. RESULTS: The mean +/- SEM level of FF cadmium
      was higher in smokers (7.93 +/- 0.16 ng/mL) than in nonsmokers (6.73 +/- 0.31
      ng/mL), and with a dose-effect of smoking. The individual levels in passive,
      light, and heavy smoking women also were higher than in nonsmoking women.
      CONCLUSIONS: Despite lack of vascularization of the follicle, cadmium
      accumulation was detectable in FF. Cadmium also could accumulate in oocytes of
      smokers; it does so, in a dose-dependent manner, in oocytes of cadmium-treated
      rats. Access to cadmium and other contaminants of cigarette smoke in FF may
      compromise the quality of oocytes, becoming a risk factor.

PMID- 7641918
TI  - Some cases of human male infertility are explained by abnormal in vitro human
      sperm activation.
AB  - OBJECTIVE: To determine if a human sperm activation assay can be used to evaluate
      males exhibiting otherwise unexplained infertility. DESIGN: Sperm from age
      matched fertile and idiopathic infertile males were assayed in the human sperm
      activation assay and the results were compared. A portion of the sperm from the
      idiopathic infertile males also was used in assisted reproductive technology
      (ART) attempts at pregnancy. PATIENTS: Idiopathic infertile couples who had
      extensive fertility testing with no identified problems that would explain their
      infertility. Fertile males that had fathered one or more children. MAIN OUTCOME
      MEASURES: Sperm nuclear decondensation-recondensation and DNA synthesis.
      Pregnancies resulting from ART using semen from a male whose sperm responded
      abnormally in the human sperm activation assay. RESULTS: Thirteen (22%) of 59
      idiopathic infertile males produced sperm that responded abnormally in the human
      sperm activation assay. Only 1 (1.7%) of 59 fertile males produced sperm that
      responded abnormally in the human sperm activation assay. The percentage of
      abnormal responders in the patient group exhibiting unexplained infertility was
      significantly higher than in the fertile male group. No sperm samples that
      responded abnormally in the human sperm activation assay resulted in pregnancies
      when used in ART. CONCLUSIONS: The human sperm activation assay is a new and
      independent indicator for some cases of infertility that otherwise would be
      unexplained. The human sperm activation assay appears to have utility in
      determining a sperm sample's efficacy for fertilization in ART attempts at
      pregnancy.

PMID- 7641919
TI  - The effect of serum from infertile women with endometriosis on fertilization and
      early embryonic development in a murine in vitro fertilization model.
AB  - OBJECTIVE: To evaluate the effect of serum from infertile women with
      endometriosis on fertilization and embryonic development in a murine IVF model.
      DESIGN: Pretreatment and post-treatment comparison of murine oocyte fertilization
      and early embryonic development with the addition of serum supplements from
      infertile women with endometriosis. SETTING: Tertiary care academic medical
      center. PATIENTS: Sera from 10 fertile women without endometriosis and 28
      infertile women with endometriosis both before and after laser laparoscopy.
      RESULTS: When compared with serum from fertile women, serum from infertile women
      with endometriosis inhibited fertilization rates (51% versus 81%) and subsequent
      embryonic development rates (46% versus 79%). The inhibitory effect was greater
      as the stage of endometriosis increased. Treatment of endometriosis by laser
      laparoscopy improved both fertilization (51% versus 56%) and early embryonic
      development rates (46% versus 58%). CONCLUSIONS: Serum from infertile women with
      endometriosis inhibits both fertilization and early embryonic development in the
      murine IVF model. Inhibition of fertilization and early embryonic development
      rates increases as the stage of endometriosis increases. Improved fertilization
      and early embryonic development rates are observed after treatment of
      endometriosis by laser laparoscopy.

PMID- 7641920
TI  - RU486 inhibits ovulation, fertilization and early embryonic development in
      rabbits: in vivo and in vitro studies.
AB  - OBJECTIVE: To clarify the role of P in ovulation, fertilization, and early
      embryonic development using RU486, a potent P receptor blocker. DESIGN: Ovulatory
      efficiency, IVF, and early embryonic development were evaluated after RU486
      administration in vivo and in vitro. SETTING: Research laboratory of a university
      hospital. PARTICIPANTS: Mature male and female New Zealand white rabbits.
      INTERVENTIONS: Animals were treated with RU486 or vehicle for 3 days before hCG
      induced ovulation. Ovaries treated with hCG to induce ovulation were perfused for
      6 hours in vitro with RU486 or vehicle. In vitro fertilization was performed in
      the presence or absence of RU486. MAIN OUTCOME MEASURES: The percentage of mature
      follicles ovulating (ovulatory efficiency) was determined after in vivo and in
      vitro treatment. Fertilization, morula, and blastocyst development were evaluated
      every 24 hours for 120 hours. RESULTS: RU486 significantly inhibited ovulation,
      fertilization, and early embryonic development. CONCLUSIONS: Progesterone plays a
      significant role in ovulation, fertilization, and preimplantation embryonic
      development.

PMID- 7641921
TI  - Modulation of anterior pituitary luteinizing hormone response to gonadotropin
      releasing hormone by insulin-like growth factor I in vitro.
AB  - OBJECTIVE: To investigate how much insulin-like growth factor I may modulate the
      LH response to GnRH. DESIGN: In primary cultures of male rat anterior pituitary
      cells, the LH response to GnRH (10(-9) M) was evaluated after a 24-hour
      preincubation with medium alone, IGF-I (1, 5, 10, 15 nM), polyclonal antibody
      anti-IGF-I (Ab-anti-IGF-I), (1:3,000; 1:10,000), or rabbit serum (1:3,000;
      1:10,000) as control. MAIN OUTCOME MEASURE: Gonadotropin-releasing hormone
      induced LH release from primary cultures of male rat anterior pituitary cells.
      RESULTS: Insulin-like growth factor I induces a dose-dependent stimulus on the LH
      response to GnRH. Insulin-like growth factor I at doses of 10 and 15 nM exerted a
      maximal stimulus, increasing the LH response to GnRH by 30%. The Ab-anti-IGF-I at
      both dilutions reduced the LH response to GnRH by 30%. No effect was exerted by
      rabbit serum. CONCLUSIONS: Present data indicate that IGF-I may enhance the
      normal LH response to GnRH from rat anterior pituitary glands, suggesting
      important influences of this growth factor in the modulation of anterior
      pituitary LH release.

PMID- 7641922
TI  - A randomized prospective comparison between intrauterine insemination and
      fallopian sperm perfusion for the treatment of infertility.
AB  - OBJECTIVE: To determine if the pregnancy rates (PRs) in infertile women could be
      improved with fallopian sperm perfusion in comparison with IUI. DESIGN:
      Randomized prospective analysis. SETTING: Academically affiliated infertility
      center. PATIENTS: Consecutive patients undergoing controlled ovarian
      hyperstimulation (COH). INTERVENTIONS: After hCG administration, patients were
      randomized to either IUI or fallopian sperm perfusion. MAIN OUTCOME MEASURES:
      Pregnancy rates with the two treatment modalities. RESULTS: Of 240 COH cycles,
      those randomized to IUI included 44 clomiphene citrate (CC) (group I) and 76
      gonadotropin (group III) cycles. Patients receiving fallopian sperm perfusion
      included 44 cycles of CC (group II) and 76 cycles of gonadotropin (group IV)
      treatment. The overall PRs per cycle (10.8% versus 10.8%) were similar for IUI
      and fallopian sperm perfusion, respectively. The PRs were also similar when
      compared for ovulation induction with CC (6.8% versus 9.1%) and gonadotropins
      (13.2% versus 11.8%). CONCLUSION: We conclude that fallopian sperm perfusion
      offers no advantage over IUI. Because the process of fallopian sperm perfusion is
      more time consuming and more costly (because of increased media usage), fallopian
      sperm perfusion does not seem indicated as a routine infertility therapy and
      should not replace IUI.

PMID- 7641923
TI  - Severe ovarian hyperstimulation despite prophylactic albumin at the time of
      oocyte retrieval for in vitro fertilization and embryo transfer.
AB  - OBJECTIVE: To report two cases of severe ovarian hyperstimulation syndrome (OHSS)
      despite the administration of 50 g IV albumin at the time of oocyte retrieval.
      Two previous published series failed to observe OHSS in patients receiving
      prophylactic IV albumin. DESIGN: Case reports of two women undergoing controlled
      ovarian hyperstimulation with E2 > 4,500 pg/mL (conversion factor to SI unit,
      3.671) on the day of hCG administration who developed OHSS despite prophylactic
      albumin administration. SETTING: The division of reproductive endocrinology at
      the Mount Sinai Medical Center. INTERVENTIONS: Fifty grams IV albumin (200 mL of
      a 25% albumin solution) were administered over 30 minutes at the time of oocyte
      retrieval. MAIN OUTCOME MEASURES: Prevention of interstitial fluid accumulation
      such as ascites, pleural effusions, and generalized edema. The other goals of
      albumin administration included avoiding hemoconcentration, renal insufficiency,
      and thrombotic complications. RESULTS: The patients developed sequelae of severe
      OHSS requiring hospitalization, despite administration of IV albumin. CONCLUSION:
      Albumin is a promising agent in the prevention of OHSS. However, until the basic
      pathophysiology of this disorder can be elucidated, the mechanism of its action
      will remain elusive. Attempts to quantify and report clinical outcomes and the
      ultimate completion of a prospective randomized study will assist in the
      prevention and management of this enigmatic disorder.

PMID- 7641924
TI  - Fertilization and pregnancy achieved by intracytoplasmic injection of sperm
      retrieved from testicular biopsies.
AB  - OBJECTIVE: To determine if intracytoplasmic sperm injection using testicular
      sperm is effective in the treatment of infertile couples with obstructive
      azoospermia. DESIGN: Case report. SETTING: Tertiary care teaching medical center.
      METHODS: Intracytoplasmic sperm injection was performed in two patients using
      testicular sperm after microsurgical epididymal sperm aspiration failed. RESULTS:
      In both cases fertilization and embryos resulted. One patient conceived and
      delivered triplets. There was no evidence of chromosomal abnormality or
      congenital malformation. CONCLUSIONS: Intracytoplasmic sperm injection using
      sperm extracted from testicular biopsy appears to be effective in the treatment
      of infertile couples with obstructive azoospermia when microsurgical sperm
      aspiration fails.

PMID- 7641925
TI  - The efficacy and cost effectiveness of embryo cryopreservation compared with
      other assisted reproductive techniques.
AB  - OBJECTIVE: To evaluate the efficacy and cost effectiveness of embryo
      cryopreservation compared with other assisted reproductive techniques (ARTs).
      DESIGN: Retrospective review of medical records and health care costs. SETTING:
      Tertiary care academic medical school ART program. PATIENTS: For determination of
      the efficacy of cryopreserved ET, we analyzed 610 patients undergoing the first
      1,000 oocyte retrievals in our program. For determination of cost effectiveness,
      we analyzed the costs associated with 334 initiated ART cycles in 1992. MAIN
      OUTCOME MEASURES: The ongoing pregnancy rate (PR) per initiated cycle and per
      oocyte retrieval. The medical costs associated with each procedure. RESULTS: The
      transfer of cryopreserved embryos increased the ongoing PR per oocyte retrieval
      by 6.6%. Transfer of cryopreserved embryos was cost effective compared with other
      ARTs. The cost per delivery for cryopreserved ETs was between 25% and 45% that of
      a fresh cycle. CONCLUSIONS: Including embryo cryopreservation in an ART program
      can improve PRs and lower the ultimate cost per delivery.

PMID- 7641926
TI  - A prospective study on the association between red hair color and endometriosis
      in infertile patients.
AB  - OBJECTIVE: To determine if red-haired infertile women have an increased
      prevalence of endometriosis. DESIGN: Prospective, nonblinded. SETTING: Large,
      metropolitan, private hospital, associated with a university. Subspeciality care
      provided by reproductive endocrinologists. PATIENTS: One hundred forty-three
      consecutive women undergoing laparoscopy or laparotomy for infertility.
      INTERVENTIONS: Laser ablation of any endometriosis present. MAIN OUTCOME MEASURE:
      Presence of endometriosis. RESULTS: Of 143 women entered into the study, 12 had
      natural red hair. The ages of these women ranged between 23 and 41 years. Ten of
      12 (83%) of the red-haired women were found to have endometriosis compared with
      55 of 131 (42%) of nonredheads. By statistical analysis, the 95% confidence
      intervals for the presence of endometriosis in redheads was 55% to 100% versus
      34% to 51% for nonredheads. CONCLUSION: The results suggest an association
      between the occurrence of natural red hair and those factors that lead to the
      development of endometriosis.

PMID- 7641927
TI  - Superimposed Image Analysis System (SIAS) software: a new approach to sperm
      motility assessment.
AB  - OBJECTIVE: To apply Superimposed Image Analysis System (SIAS) software (Delta
      Sistemi, Rome, Italy) to the objective analysis of sperm motility. DESIGN: To
      test a new procedure for sperm motility assessment based on image
      superimposition. RESULTS: The system can superimpose six sequential frames onto a
      monitor producing a final image with a motion effect similar to the multiple
      exposure photography method, but bypassing the film processing stage. Viewing the
      final image of a complete series of six superimposed frames allows the evaluation
      of the percentage of motile spermatozoa and their kinetic characteristics.
      Compared with multiple exposure photography, SIAS has the following main
      advantages: [1] the procedure is quick; [2] projecting the first frame alone
      allows the easy evaluation of sperm concentration; and [3] the system allows
      quick and easy analysis and measurement of each sperm trajectory frame by frame,
      thus avoiding misleading interpretations because of crossing sperm trajectories,
      collisions, and overlapping of motile spermatoza with round cells or immotile
      spermatozoa. CONCLUSIONS: Superimposed image analysis is a new approach to sperm
      motility assessment. It seems to be useful particularly in selected situations,
      such as oligozoospermia or in cases of increased round cell concentration. In
      these situations, SIAS can even serve as a support or an alternative to the
      computer-aided sperm analysis system widely used for objective sperm analysis.

PMID- 7641928
TI  - Spermoculture: improvement of the bacteriological quality of samples by direct
      verbal counseling before semen collection.
AB  - OBJECTIVE: To compare the bacteriologic quality of samples after direct verbal or
      written counseling for semen collection. DESIGN: Prospective randomized
      comparative study. SETTING: Laboratories of biology of reproduction and
      microbiology in university hospitals. PATIENTS: Male partners of infertile
      couples on their first attempt to collect semen were assigned randomly into two
      groups. INTERVENTION: In one group (n = 52) the patients were given direct verbal
      instruction by one of the investigators on how to avoid bacterial contamination
      during semen collection. In the other group (n = 52) the patients were asked to
      follow the usual written instructions. MAIN OUTCOME MEASURE: Bacterial count,
      number of species, classification of the samples in positive, negative, and
      noninformative cultures. RESULTS: Direct verbal teaching significantly reduced
      the bacterial count (2.06 +/- 1.6 versus 3.29 +/- 1.6 log cfu/mL; mean +/- SD)
      and number of species (1.44 +/- 2.02 versus 3.25 +/- 2.25), increased the
      percentage of sterile cultures (59.6% versus 23.1%), and decreased the percentage
      of noninformative cultures (29.9% versus 50%). CONCLUSION: Direct verbal
      counseling on how to avoid bacterial contamination during semen collection
      significantly improves the bacteriologic quality of the samples.

PMID- 7641929
TI  - Menses cup evaluation study.
AB  - OBJECTIVE: To determine whether the menses cup is well tolerated by menstruating
      women. DESIGN: Prospective descriptive clinical study. SETTING: Normal human
      volunteers in an academic research environment. PARTICIPANTS: Fifty-one
      menstruating women recruited between June to December 1991. INTERVENTIONS: Each
      participant was provided with two menses cups and an instruction sheet. Baseline
      information, including age, occupation, martial status, parity, description of
      menstrual flow, and current method used to cope with menstrual flow was
      collected. Subjects were asked to describe their experience with the cup at 1-, 2
      , 6-, and 12-month intervals. MAIN OUTCOME MEASURE: The proportion of women who
      found the cup acceptable. RESULTS: The cup was used by 51 subjects for a total of
      159 cycles. Overall, 23 women (45%) found the cup an acceptable method for coping
      with menses. Among 29 (57%) women who used the cup for two or more cycles, 62%
      found it acceptable. CONCLUSION: The menses cup may be an acceptable method for
      some women for coping with menstrual flow.

PMID- 7641930
TI  - Ultrasound guidance for intrauterine surgery.

PMID- 7641931
TI  - Mechanism of insulin resistance.

PMID- 7641932
TI  - A question of terminology.

PMID- 7641934
TI  - Public health nursing: what it is and what it's not!

PMID- 7641933
TI  - A focus on managed care trends.

PMID- 7641935
TI  - Nurse practitioners and private practice.

PMID- 7641936
TI  - It's not enough to be right.

PMID- 7641937
TI  - What's to become of "General Hospital"?

PMID- 7641938
TI  - Patient care documentation: today and tomorrow.

PMID- 7641939
TI  - Does a program in research evolve or is it developed?

PMID- 7641940
TI  - Heat-induced structural changes in the Fab fragment of IgG recognized by
      molecular dynamics stimulation--implications for signal transduction in
      antibodies.
AB  - Molecular dynamics simulation was used to identify the conformational alterations
      in the Fab fragment (Kol), driven by heating at 300, 320, and 340 K. Comparison
      of heat-modified VH,CH1 and VL,CL domain structures with the corresponding
      crystal conformations revealed specific differences, most definitely expressed in
      the CH1 domain. These are dislocations of predominantly peripheral peptide loops
      exposed to the V-C interdomain interface, comprising in particular the 175-185
      amino acids of the heavy chain, as well as the 112-123 amino acids of the
      interdomain hinge fragment. The deviations, limited to peripheral domain regions
      at 300 and 320 K, spread at 340 K. The resulting relaxation of the tertiary
      packing in the protein (including the hydrophobic core) initiates global melting
      of the domain. These theoretical results were supported by experimental findings
      concerning penetration and binding of dyes (Congo Red, Trypan Blue, ANS) to the
      protein. Packing relaxation of the CH1 domain is turned on after disruption of
      the specific peptide arrangement formed at the V-C interdomain interface
      basically at the hinge portion (117-122) and at fragments of adjacent peptide
      loops (149-154, 171-179) of CH1 origin, most probably playing the role of a
      switching mechanism. The dislocations also comprise the 131-141 amino acids of
      the loops accommodated at the CH1-CH2 interface. However, the lack of
      crystallographic data concerning the Fab-Fc interface limits discussion of this
      effect to speculation. It was concluded that the unconcerted movements of the V
      and C parts of the Fab fragment are an intrinsic driving mechanism, introducing
      structural alterations into the C domains. It is suggested that the domain
      relaxation, induced by heating or mechanical constraints, allows for
      intermolecular interactions, affecting in this way the stability of the immune
      complex.

PMID- 7641941
TI  - Computer modelling of polymer decomposition by active interactions with enzyme
      molecules. A simulation of RNA digestion by ribonuclease.
AB  - A model of 200 polymer molecules each 70 units of length with randomly located
      susceptible and resistant links was elaborated. The production of mono-, di-, tri
      unit and other fragments in repeating random interactions of polymer (P) with the
      polymer--cleaving enzyme (E) was calculated. Analysis of the calculations
      performed that the polymer molecules with an initial count of 70-units
      disappeared, imitating the first order kinetics with a half-life of about 0.37 x
      10(3) P/E interactions. The production of fragments 30-69 units long was small
      and the life of those molecules was limited to a range from 0.5 x 10(3) to 5 x
      10(3) P/E interactions. The mean polymer length decreases to one third at 10(3)
      P/E interactions. The production of single-unit fragments followed a sigmoidal
      relationship. The first reaction period, with increasing number of single-unit
      fragments per 10(3) P/E interactions, corresponded to a decrease in the mean
      polymer length to about 10 units. Then the production of one-unit fragments
      decreased and stopped at about 10(5) P/E interactions. This model could be used
      for analysis of RNA fragmentation processes by any number of RNA-ribonuclease
      interactions. Further development of this model would be of help in understanding
      the effect of various nucleotide sequences on the RNA digestion process.

PMID- 7641942
TI  - Analysis of genetic markers Svp-1 and Svp-3 in recombinant mouse strains CBXE and
      EXCB.
AB  - New genetic markers; seminal vesicle proteins (Svp-1, Svp-3) and agouti (A) locus
      were tested in five RI EXCB and 15 RI CBXE strains developed from CBA/Kw and KE
      inbred strains of mice. For agouti and Svp-1 loci, on the chromosome 2, there are
      five recombinant strains out of 20 strains which gives r = 0.1. It is close to
      the known map distance (10cM) between these two loci.

PMID- 7641943
TI  - Effect of low-energy laser power on the bone marrow of the rat.
AB  - The effect of low power laser light upon the haematopoietic system of rats and
      also upon the basic haematological parameters was studied. A HeliumNeon
      continuous emission laser (632.8 nm; max. power 5 mW) and a Galium arsenide
      semiconductor pulse laser (904 nm; power 80 mW; pulse duration 200 ns) were used
      as light sources. Intact skin on the hind legs of rats was exposed, over a
      section of the femur. Peripheral blood analysis carried out before and after the
      experiments. These indicated that AsGa laser light induced a decrease in bone
      marrow mastocytes and peripheral blood basophils with an increase in the number
      of eosinophils. An increase in mitotic activity in the bone marrow was observed
      in the exposed groups of animals. No significant changes in Hb, Ht, erythrocyte
      or reticulocyte levels in the peripheral blood were noted, nor was there an
      increase in megakaryocyte emperipolesis.

PMID- 7641945
TI  - Sidelining dental care in the NHS.

PMID- 7641944
TI  - The effect of the pollen extracts quercitin and cernitin on the liver, lungs, and
      stomach of rats intoxicated with ammonium fluoride.
AB  - Quercitin and Cernitin are not in themselves toxic to rats. When administered at
      the time of intoxication of the animals with ammonium fluoride, they reduced the
      noxious effects of the toxic agent in the liver and lungs. It is suggested that
      Quercitin and Cernitin might play a protective role during prolonged exposure to
      ammonium fluoride. Neither ammonium fluoride nor Quercitin or Cernitin seem to
      exert any effect on the stomach.

PMID- 7641946
TI  - The dental impact of eating disorders.
AB  - Our self-perceptions are all influenced to some extent by the media. The increase
      in sales of diet plans immediately after Christmas only serves to highlight the
      fact that many people (consciously or subconsciously) are aware of the effect
      that advertisements have on our lives. The weight of most people is controlled by
      a combination of diet and homoeostatic control and remains relatively constant,
      but weight loss has a more profound and sinister effect for others. Unexplained
      dental erosion can occasionally be found during dental examinations and, despite
      careful questioning, a definitive diagnosis may prove elusive. In these patients,
      once the more common causes of dental erosion have been eliminated, the eating
      disorders should be considered. In this paper, the effects of psychological
      conditions affecting the diet on the dentition will be discussed.

PMID- 7641947
TI  - Provisions of dental services in the Scottish Islands.
AB  - Health Board General Managers have overall responsibility for the efficiency,
      effectiveness and economy of the management of dental services within their area.
      In Scotland, six health boards cover islands with a total population of over
      80,000. This article looks at the island areas in Scotland which have unique
      difficulties.

PMID- 7641948
TI  - Periodontal considerations in restorative dentistry. 1: Operative considerations.
AB  - Restorative dentistry may be defined as the branch of dentistry that deals with
      the restoration or replacement of lost tooth structure, teeth or oral tissues.
      The practice of restorative dentistry has a reciprocal relationship with the
      maintenance of periodontal health. Untreated periodontal disease will compromise
      the success of restorative dentistry, and poor restorative treatment may have
      adverse effects on the periodontium by increasing accumulation of plaque and
      inducing changes in the composition of the plaque flora. Excessive occlusal
      stress and direct physical injury to the gingiva produced by the various dental
      procedures may also affect periodontal health. This is the first of two articles
      to look in depth at the periodontal considerations necessary in restorative
      dentistry, and covers the factors important in operative dentistry. The second
      article, which will be published in a later issue, will look at the situation
      with regard to prosthodontics.

PMID- 7641949
TI  - The early treatment of posterior crossbites: a review of continuing
      controversies.
AB  - A posterior crossbite may pose long-term risk through causing associated
      displacement in the mandibular path of closure. In this paper the authors review
      the current opinions on treatment of such a problem.

PMID- 7641950
TI  - Missing anterior teeth: treatment options and their orthodontic implications.
AB  - Recent advances in restorative and surgical materials and techniques have
      increased the treatment options available for patients who are missing an
      anterior tooth. The factors influencing the management of such patients and the
      orthodontic implications of these treatment options are discussed in this paper.

PMID- 7641951
TI  - From the cradle to the grave?

PMID- 7641952
TI  - An update on conventional fixed bridgework. Part 4: Clinical techniques.
AB  - The first three articles of this series have emphasized the importance of careful
      treatment planning in conventional fixed bridgework. In this, the fourth article,
      attention to detail continues to be the theme. The clinical procedures for fixed
      bridgework (tooth preparation, temporization, impression taking and occlusal
      registration) will be discussed.

PMID- 7641953
TI  - Update on fissure sealants.
AB  - The pit and fissure sealants that are commercially available today are designed
      to prevent plaque, bacteria and carbohydrates from entering the fissures and
      causing caries. This article will concentrate on contemporary diagnostic problems
      and indications for fissure sealing. Brief mention will be made of innovations in
      materials and techniques.

PMID- 7641954
TI  - Apex locators in endodontics: which, when and how?
AB  - To ensure that root canal treatment is successful the clinician must accurately
      determine the working length of the root canal. Traditionally this has been
      determined using radiography, but electronic apex locators are increasingly being
      used. This article describes the locators available, the principles behind their
      use and gives guidelines on how and where to use them.

PMID- 7641955
TI  - Dental prescribing.
AB  - Dental surgeons, who are entitled to prescribe drugs to their patients, have a
      duty to be conversant with the rapid changes occurring in pharmacology and to
      inform their patients about the proper use of the medicines they are given. This
      article outlines the sources of information on drugs that are available to dental
      practitioners, especially the Dental Practitioners' Formulary.

PMID- 7641956
TI  - Oral lichen planus and chronic active hepatitis B: a salutary tale.
AB  - Oral lichen planus is occasionally associated with chronic active hepatitis or
      primary biliary cirrhosis. This paper describes a patient who presented with oral
      lichen planus and proved to have chronic active hepatitis, evidently related to
      hepatitis B virus infection. Oral lichen planus appears occasionally to be
      associated with systemic infection with hepatitis B or hepatitis C viruses,
      particularly in patients from southern Europe.

PMID- 7641957
TI  - The preschool child: practical treatment planning.
AB  - The preschool years extend from birth up to the age of 4 years and represent the
      time of most rapid growth and development. During this period the child
      progresses from the edentulous state to having a fully erupted and functional
      primary dentition. Also during the preschool years important stages in
      development of underlying permanent teeth occur. Good management of the preschool
      child is an excellent practice builder: it leads to a motivated patient, happy to
      undergo any treatment necessary, and encourages confidence and improves the
      attitudes to oral health of other members of the family.

PMID- 7641958
TI  - Sodium hypochlorite injection into periapical tissues.
AB  - The following case report demonstrates the tissue changes that may occur when
      sodium hypochlorite, an irrigant used for debridement of the root canal system,
      is inadvertently injected into periapical tissues.

PMID- 7641959
TI  - Oral administration of methylergometrine shows a late and unpredictable effect on
      the non-pregnant human menstruating uterus.
AB  - OBJECTIVE: To study the pharmacodynamic and pharmacokinetic properties of oral
      and intravenous methylergometrine upon uterine motility during menstruation.
      STUDY-DESIGN: Intra-uterine pressure was measured in six volunteers with a fluid
      filled sponge-tipped catheter during menstruation. Methylergometrine was given
      orally (0.5 mg) or intravenously (0.2 mg) in a cross-over design. RESULTS: After
      intravenous administration, a fast increase of the frequency of uterine
      contractions and basal tone occurred with a decrease of amplitude, lasting at
      least 30 min. Oral administration had a late and less marked effect on uterine
      motility. An intravenous dose administered 24 h after an oral dose had no effect
      on uterine motility. Pharmacokinetic data, such as the maximum plasma
      concentration (Cmax), the time at which Cmax is reached (tmax) and the half-life
      of absorption (t1/2abs) also demonstrated large individual variations after oral
      administration. CONCLUSIONS: Oral administration of methylergometrine had an
      unpredictable and late effect on uterine motility on the menstruating uterus,
      probably due to an unpredictable bioavailability, in contrast with the fast and
      predictable effect after intravenous administration.

PMID- 7641960
TI  - History of ergot alkaloids from ergotism to ergometrine.
AB  - Epidemics of ergotism occurred frequently in the Middle Ages. They were a source
      of inspiration for artists and were popularly known as 'St. Anthony's Fire',
      resulting in gangrene, neurological diseases and death. It was caused by eating
      rye bread contaminated with the fungus claviceps purpurea. In 1582 it was
      described that a delivery could be hastened by administering a few spurs of the
      secale cornutum. The dosage was, however, very inaccurate resulting in frequent
      uterine ruptures. The nickname of the preparation of 'pulvis ad partum' was
      changed to 'pulvis ad mortem'. Therefore, after 1828 the ergot alkaloids were no
      longer used during delivery but only as a measure to prevent postpartum
      haemorrhage. From 1875 onwards many derivatives of ergot alkaloids were found.
      Dudley and Moir isolated ergometrine in 1932. It proved to have a very specific
      uterotonic action. However, because of severe and unpredictable side effects and
      the instability of the drug, ergometrine is not the drug of choice for either the
      prevention or the treatment of postpartum haemorrhage.

PMID- 7641961
TI  - Primary application of three-dimensional ultrasonography to early diagnosis of
      ectopic pregnancy.
AB  - OBJECTIVE: Preliminary evaluation of three-dimensional (3D) imaging for early
      diagnosis of ectopic pregnancy. STUDY DESIGN: Twelve asymptomatic patients before
      six weeks of amenorrhea and with no feature of intrauterine nor of ectopic
      pregnancy at traditional bidimensional ultrasonography were considered.
      Laparoscopy showed ectopic pregnancy in 9 cases. RESULTS: 3D transvaginal
      ultrasonography preceding laparoscopy showed small ectopic gestational sac in 4
      cases. Moreover the fallopian tube on the side of ectopic pregnancy could be
      imaged in all cases. This was possible because the fallopian tube was surrounded
      by a fine hypoechogenic border, an apparently specific feature which had not been
      reported previously. CONCLUSION: These preliminary data suggest that 3D
      ultrasonography is an effective procedure for early diagnosis of ectopic
      pregnancy in asymptomatic patients before six weeks of amenorrhea.

PMID- 7641963
TI  - Factors predicting labour onset in patients treated with prostaglandin E2 for
      cervical ripening.
AB  - The aim of this study is the evaluation of predictive factors in the onset of
      labour after pre-induction cervical ripening with prostaglandins. We enrolled 112
      consecutive singleton term pregnancies (37-42.3 weeks) with unfavourable cervix
      and intact membranes, requiring induction of labour because prolonged pregnancy
      (59%) or maternal/fetal complications (41%). Treatment consisted of the cervical
      application (once or twice, 12 h apart) of prostaglandin E2 gel (Upjohn, Italy).
      Uterine activity was monitored by external cardio-tocography before and during
      the next 2 h. Two patients showed uterine hyperstimulation and acute fetal
      distress requiring caesarean section. Sixty percent of patients went to labour
      and delivered without further stimulations. In this group the rate of caesarean
      section (9.1%) was lower than in patients failing to onset labour (68.2%).
      According to the logistic regression three factors positively predicted the onset
      of labour: first-hour uterine contractility, basal uterine activity and
      gestational age. The first-hour contractility in particular, represents the
      myometrial sensitivity to prostaglandin E2 and may become a practical marker of
      spontaneous onset of labour in patients undergoing cervical ripening.

PMID- 7641964
TI  - First trimester fetal heart rate measurements by transvaginal ultrasound combined
      with pulsed Doppler: an evaluation of 1331 cases.
AB  - The aim of this study is to present the cardiac activity measurements obtained
      from 1331 embryos and first trimester fetuses in whom the crown-rump length (CRL)
      measurements were between 2 and 60 mm, and to correlate the pattern of changes
      according to growth in body length, with an objective and reliable technique;
      transvaginal ultrasound combined with pulsed Doppler. Sonographic examinations
      were performed using a Combison 320-Kretz scanner with a 5-7.5 MHz vaginal probe
      with 240 degrees scanning angle, combined with a 4.5 MHz pulsed Doppler. As the
      embryo grows, the mean heart rate increases sharply, from 106.8 +/- 6.4 at a CRL
      of 2 mm to 178.3 +/- 7.0 at a CRL of 23 mm; followed by a plateau and a slight
      decline thereafter. Statistical analysis of the body length and corresponding
      heart rate revealed a relationship with a correlation coefficient of 0.61 (P <
      0.01), whereas relationship between CRL < or = 23 and corresponding heart rate
      was striking with a correlation coefficient of .87 (P < 0.01).

PMID- 7641962
TI  - Change in alcohol, tobacco and coffee consumption in pregnant women: evolution
      between 1988 and 1992 in an area of high consumption.
AB  - OBJECTIVE: Analyse the evolution of alcohol, tobacco and coffee consumption
      during pregnancy in a population characterized by a high level of consumption and
      a low socioeconomic situation. STUDY DESIGN: Data were obtained from two studies
      done with the same protocol and questionnaire in the Roubaix Public Maternity
      Hospital in 1988 (176 women) and 1992 (235 women); the two periods were compared
      using univariate tests and multiple logistic regression to control for social
      factors. RESULTS: Between 1988 and 1992, there was a clear decrease in alcohol
      consumption, a slight decrease in coffee consumption and an increase in tobacco
      use. These changes affected usual consumption as well as consumption during
      pregnancy. The increase in tobacco use was no longer significant after
      controlling for social factors. However, the decrease in alcohol consumption
      affected all women regardless of sociodemographic characteristics, and remained
      significant after controlling for these characteristics. CONCLUSION: Several
      factors support the hypothesis that the decrease in the reported alcohol
      consumption is real, for consumptions in the low to moderate range. However, it
      is difficult to identify the role of the several factors involved in this
      evolution: behaviour of the general population, attitude among pregnant women,
      information and sensitization of prenatal care providers. Besides, one negative
      aspect needs to be considered: the stability of the incidence of fetal alcohol
      syndrome, probably reflecting the stability of the proportion of very heavy
      consumers.

PMID- 7641965
TI  - Maternal plasma level of thrombomodulin is increased in mild preeclampsia.
AB  - The purpose of this study was to determine if plasma thrombomodulin levels, a
      glycoprotein found on the surface of the endothelial cell, are elevated in
      pregnant women with mild preeclampsia and if these levels correlated with other
      features of disease severity. Parameters were compared in three groups of women:
      (I) 30 pregnant women with mild preeclampsia, (II) 30 normotensive pregnant women
      of similar lengths of gestation, and (III) 30 normotensive healthy young women.
      Thrombomodulin levels were significantly elevated in women with preeclampsia as
      compared with those of gestation-matched pregnant and non-pregnant controls.
      There was no correlation between plasma thrombomodulin levels and creatinine and
      uric acid blood levels. It is thus suggested that plasma thrombomodulin levels
      are elevated in preeclampsia, even in its mild stage, reflecting a vascular
      endothelial damage.

PMID- 7641966
TI  - Maternal and perinatal complications in triplet compared with twin pregnancy.
AB  - OBJECTIVE: To compare maternal and perinatal complications in triplet and twin
      pregnancies. STUDY DESIGN: Case-controlled study in the setting of a University
      Hospital. Each pregnancy of a consecutive series of 40 triplet pregnancies of 20
      weeks or more was matched for parity and maternal age with two sets of twins
      delivered in the same year. Primary end points of the analysis were maternal
      complications and perinatal outcome. RESULTS: Of the triplets 82% and of the
      twins 36% were a result of assisted reproduction. Pre-term labor occurred
      significantly more often in triplet than in twin gestation. Triplets had a
      significantly lower median birth-weight (1478 vs. 2030 g) and gestational age at
      delivery (32 vs. 35.5 weeks). The mean neonatal hospital stay was significantly
      longer in triplets, mainly related to the lower birth-weight, but there was no
      significant difference between triplets and twins in the incidence of major
      neonatal complications. CONCLUSION: This data of the anticipated perinatal
      outcome in triplet and twin pregnancies may be used to counsel women with a
      triplet pregnancy considering selective reduction to twins. All methods of
      assisted reproduction should aim at prevention of multifetal gestation.

PMID- 7641967
TI  - The development of a local symphysis-fundal height chart in a rural area of
      Tanzania.
AB  - In this prospective community-based study, a symphysis-fundal height chart was
      constructed, derived from 403 measurements in 83 women, in a local rural
      population. Using the recommended Cardiff chart, 132 measurements (32.9%) were
      below the 10th centile line, while only two measurements were above the 90th
      centile line. This may indicate that a high percentage of the Tanzanian fetus are
      growth retarded or genetically small. The relative importance of each of these
      remains unknown. Use of the Cardiff chart in rural Tanzania could result in
      unnecessary referrals, which is undesirable in view of both the women involved
      and strained resources. Therefore, the use of a symphysis fundal height chart,
      based on measurements in the local population, is recommended.

PMID- 7641968
TI  - Dinoprostone priming of the cervix prior to termination of midgestation pregnancy
      with sulprostone.
AB  - OBJECTIVE: To determine if cervical ripening with the prostaglandin E2 analogue
      dinoprostone effectively shortens the induction-to-delivery interval in
      midpregnancy terminations with sulprostone. STUDY DESIGN: We retrospectively
      studied 100 women admitted for pregnancy termination at midgestation because of
      fetal anomalies between September 1989 and January 1993. Three regimens were
      used: 27 women received intramuscular sulprostone only, 29 women received
      intravenous sulprostone only, and 44 women received intravenous sulprostone after
      cervical priming with dinoprostone. Wilcoxon's rank sum test was used for
      statistical analysis. RESULTS: Dinoprostone priming did not significantly reduce
      the induction-to-delivery interval in either parous or nulliparous women.
      However, when divided into first and subsequent pregnancies, we found that
      primigravidae, but not multigravidae, had an induction-to-delivery interval that
      was significantly shorter by approximately 10.5 h when pretreated with
      dinoprostone. CONCLUSION: Dinoprostone priming of the cervix prior to termination
      of midgestation pregnancy with sulprostone (Nalador) effectively shortens the
      induction-to-delivery interval in women in their first pregnancy.

PMID- 7641969
TI  - Vagino-levator reflex: description of a reflex and its role in sexual
      performance.
AB  - A new reflex, termed the 'vagino-levator reflex', was studied in 17 healthy women
      (mean age 36.6 years). The vagina was distended with up to 300 ml air in a condom
      tied to a catheter, and the levator ani response was determined by means of
      needle electrode introduced into the muscle. The test was repeated after
      anesthetizing the vagina and the levator muscle, respectively. The levator EMG
      activity rose when the vagina was distended; the amplitude and duration of
      activity increased in parallel with vaginal distension. The levator response did
      not occur after successive repetition of vaginal distension due probably to
      levator muscle fatigue; nor did it occur after anesthetizing the vagina or the
      levator muscle. The mean latency of the reflex was 39.5 ms. The vagino-levator
      reflex seems to play a role in the sexual act. Levator contraction upon penile
      thrusting leads to genital responses that could facilitate sexual performance.
      These responses comprise widening of the vaginal introitus, vaginal elongation
      and ballooning of the upper vagina as well as uterine elevation. Vagino-levator
      reflex dysfunction may result in disorders of sexual act.

PMID- 7641970
TI  - Clinical and subclinical varicocele: a useful distinction?
AB  - OBJECTIVE: The purpose of the study was to establish whether it is useful to make
      a distinction between clinical and subclinical varicoceles with a view to
      deciding for treatment or not. Therefore, we compared our results of treatment of
      clinical vs. subclinical varicoceles. STUDY DESIGN: The changes of semen
      parameters and the occurrence of pregnancies in 40 infertile men treated for
      clinical varicocele were compared with those in 46 infertile men treated for
      subclinical varicocele. The significance of individual semen changes was analysed
      by paired t-test in both groups and the results of both groups were compared by
      analysis of covariance. The pregnancy rates were calculated and the life table
      curves of pregnancy of both groups were compared. RESULTS: There were
      statistically significant increments in sperm density, motility and morphology
      both after treatment of clinical and subclinical varicoceles, and these
      increments did not differ significantly between both groups. The cumulative
      pregnancy rates after a mean follow-up period of 6.6 years amounted to 42.5% for
      clinical varicoceles and to 39.1% for subclinical varicoceles and the life table
      curves of pregnancy ran a rather similar course in both groups. CONCLUSION: We
      conclude that there is no reason to emphasize the palpatory findings in infertile
      men with varicocele.

PMID- 7641971
TI  - Relaxant effects of nitric oxide and cyclic GMP on pregnant rat uterine
      longitudinal smooth muscle.
AB  - The purpose of our study was to examine the relaxant effects of sodium
      nitroprusside (SNP) and cyclic guanosine 3'-5'-monophosphate (cGMP) on pregnant
      rat myometrium. Using very thin muscle strips, which allows diffusional access of
      applied drugs (in a few seconds), contractile properties were examined. This
      technique facilitates study of SNP's effects on uterine contractility as nitric
      oxide is rapidly inactivated to NO2. SNP did not decrease the amplitudes of 45
      mmol/l KCl contractions but decreased spontaneous contractions and 1 mumol/l
      carbachol contractions. The relaxation of carbachol contractions by SNP were
      antagonized by methylene blue. In addition, 8-bromo-cyclic guanosine
      monophosphate (8-bromo-cGMP) also inhibited KCl-, carbachol- and oxytocin-induced
      contractions, however, the relaxant effect of 8-bromo-cGMP was much greater on
      carbachol and oxytocin contractions than on KCl contractions. Cyclic GMP (1
      microM) decreased contractions evoked by various concentrations of Ca2+ and
      carbachol with 1 mumol/l GTP-gamma S in skinned (membrane-permeable) strips.
      These results demonstrate that SNP stimulates guanylate cyclase to produce cGMP
      and that the relaxant effect of cGMP was predominant on pharmaco-mechanical
      coupling. The cyclic-GMP system may help in maintaining pregnancy and preventing
      uterine contractions during exposure to stimulating agonists.

PMID- 7641972
TI  - Urinary trypsin inhibitor suppresses premature cervical ripening.
AB  - Unknown signals from the fetus are thought to be involved in the onset of
      parturition. We recently discovered that urinary trypsin inhibitor (UTI) from
      fetal urine inhibits uterine muscle contraction. OBJECTIVES: The aim of this
      research was to elucidate the mechanism of action of UTI in suppressing cervical
      maturation. STUDY DESIGN: Non-pregnant and pregnant rabbits pretreated with and
      without UTI suppositories containing 1000 U (400 micrograms) for 3 days were
      treated for 2 days with vaginal suppositories containing 100 ng of interleukin-8
      (IL-8). RESULTS: IL-8 induced softening and dilatation of the rabbit cervices. In
      contrast UTI inhibited IL-8 induced cervical softening and dilatation. Water
      content, collagen content, neutrophil counts, elastase activity and collagenase
      activity of the cervix were increased by IL-8, but they did not increase by IL-8
      with UTI. CONCLUSION: These results suggest that UTI inhibits cervical maturation
      induced by IL-8.

PMID- 7641973
TI  - Successful treatment of a cervical pregnancy with a single low dose methotrexate
      regimen.
AB  - Until very recently cervical pregnancies have been treated with surgery, usually
      hysterectomy. The development of endovaginal ultrasound, which allows early
      diagnosis, and methotrexate chemotherapy have opened up new therapeutic options.
      A 45-year-old multigravida presented at 8 weeks' gestation with vaginal bleeding.
      Endovaginal ultrasound demonstrated a cervical pregnancy with a fetal pole, 1.2 x
      1.4 cm sac, no cardiac pulsations, and an empty uterus. After discussion with the
      patient, single low dose methotrexate 1.5 mg/m2 was given intramuscularly. The
      patient's hCG titre was 5882 IU-(Third International Standard). Over a 5-week
      period the hCG titres fell, and the gestational sac disappeared. The patient
      experienced intermittent vaginal bleeding and cramping but was managed as an
      outpatient. Single low dose methotrexate may be a successful management option in
      selected cases of cervical pregnancy.

PMID- 7641974
TI  - Management of persistent lymphocele by sclerotherapy with doxycycline.
AB  - Three cases of lymphocele after lymphadenectomy for gynecologic malignancy are
      presented. These patients had large, symptomatic lymphoceles resistant to
      percutaneous catheter drainage. Sclerotherapy with a single dose of doxycycline
      was administered percutaneously to each patient. Single treatment achieved
      resolution in two patients. The third had a persistent lymphocele requiring
      excision. To our knowledge, doxycycline has not been used for sclerotherapy for
      lymphocele following radical gynecologic surgery. It may represent a viable
      addition to the conservative management of lymphoceles.

PMID- 7641975
TI  - Pre-eclampsia and trisomy 13.
AB  - A 41 year old multiparous woman with an uncomplicated obstetric history was
      referred because of pre-eclampsia. As ultrasonic examination revealed severe IUGR
      and multiple congenital anomalies, trisomy 13 was suspected and confirmed by
      amniocentesis. This chromosomal anomaly should be suspected in cases where pre
      eclampsia is associated with abnormal fetal morphology.

PMID- 7641976
TI  - Multiple signal transduction pathways regulate discoidin I gene expression in
      Dictyostelium discoideum.
AB  - The expression of the discoidin I genes in Dictyostelium discoideum is regulated
      by the concerted action of the extracellular factors cyclic adenosine
      monophosphate (cAMP), folate, prestarvation factor (PSF) and conditioned media
      factor (CMF). However, the pathways by which these signals are transduced and the
      interactions between the pathways have been unexplored so far. We have analysed
      wild-type and mutant cells with defined lesions in signal transduction to
      elucidate these regulatory processes, and shown that different pathways are used
      for the down-regulation and induction of these genes. The cAMP receptor cARI is
      required for the cAMP-mediated down-regulation of discoidin I gene expression but
      not for the induction of discoidin I expression during development. Surprisingly,
      induction of the discoidin I genes requires G alpha 2, the G-protein subunit
      which is generally believed to couple to cARI, to control the expression of cAMP
      inducible genes. Thus, our data suggest that G alpha 2 interacts with different
      receptors to regulate gene expression in early development. Furthermore, the
      analysis shows that discoidin induction in bacterially grown cells occurs in two
      sequential steps. The first is a low basal induction which occurs in late log
      phase growth prior to starvation. PSF can induce the basal level, and the
      induction is independent of G alpha 2. The developmental induction following
      starvation is much stronger, dependent on G alpha 2 and probably signaled by CMF,
      which is secreted at that time.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7641978
TI  - Cardiac myosin heavy chain expression during heart development in Xenopus laevis.
AB  - Muscle-specific gene expression in the heart during Xenopus development was
      investigated using reverse transcription-polymerase chain reaction (RT-PCR) and
      whole-mount in situ hybridization to detect transcripts of the gene for the
      cardiac myosin heavy chain (CMHC). RT-PCR analysis determined that CMHC
      transcripts are present in the cardiac mesoderm at state 13, demonstrating that
      muscle-specific gene expression in the primitive myocardium has begun by the
      early neurula stage, approximately 30 h before the heart beat begins. Xenopus,
      therefore, is similar to amniotes and mammals in that cardiac precursor cells
      begin to express muscle-specific gene transcripts soon after commitment to the
      cardiac myocyte lineage. The earliest CMHC gene transcripts can be detected in
      the heart using whole-mount in situ hybridization is early tailbud stage 28,
      which coincides with the onset of heart tube morphogenesis. CMHC gene expression
      was also detected in skeletal muscle: RT-PCR analysis determined that CMHC
      transcripts are transiently expressed in the somite during the initial phases of
      skeletal muscle differentiation. Furthermore, CMHC mRNAs are expressed in a
      subset of head muscles of the feeding tadpole. CMHC gene expression is induced in
      ectodermal cells of the animal cap in blastula-stage embryos injected with
      synthetic MyoD or Myf5 RNA, suggesting that the CMHC gene contains regulatory
      elements that are responsive to the activity of those skeletal-muscle-specific
      transcription factors.

PMID- 7641977
TI  - Comparison of the Dictyostelium rasD and ecmA genes reveals two distinct
      mechanisms whereby an mRNA may become enriched in prestalk cells.
AB  - The Dictyostelium ras gene, rasD, encodes an mRNA that is more abundant in
      prestalk than prespore cells in the migratory slug. Its expression is inducible
      by extracellular cAMP but is not inducible by the prestalk and stalk cell
      morphogen differentiation inducing factor (DIF). We show that a rasD-lacZ fusion
      gene is first expressed in approximately one half of the cells in the aggregate,
      including some cells that also express a prespore-specific marker. The amount of
      rasD-lacZ fusion protein in prespore cells then diminishes as the slug is formed.
      Analysis of a rasD-lacZ fusion protein with an N terminal substitution that
      reduces protein stability within the cell provides strong confirmatory evidence
      that the ras gene product becomes enriched in prestalk cells by selective
      repression of gene expression in prespore cells. In contrast, the DIF-inducible
      ecmA gene is expressed only in those cells that will become prestalk cells in the
      migratory slug. These results show that there are two different ways in which an
      mRNA may become enriched in prestalk cells and support the view that DIF is the
      inducer of prestalk cell differentiation.

PMID- 7641980
TI  - Retinoic acid provokes metaplasia of epithelium formed in vitro by adult human
      epidermal keratinocytes.
AB  - A striking effect of retinoids is their ability to alter cell fate during
      development. The mucous metaplasia produced by treating chick embryo skin in
      organ culture with retinoic acid is a classical example of this property. It has
      been impossible so far to demonstrate that retinoids are able to provoke
      metaplasia of adult keratinocytes grown in vitro, although these agents have been
      shown to block terminal epidermal differentiation, to induce increased synthesis
      of mucopolysaccharides, and to induce the ectopic expression of K19 and K13
      keratins. Our previous work showed that adult human epidermal keratinocytes grown
      on dermal equivalents at the surface of a culture medium containing physiological
      amounts of retinoids form a normal keratinized epidermis, while when excess
      retinoic acid is added to the culture medium, keratinization is prevented but
      stratification is not. Here we show that the distribution of tissue- and
      differentiation-stage-specific markers in retinoic acid-treated epithelium is
      similar to that of the oral mucosa. Moreover, when the excess retinoic acid is
      removed, a new epithelium is formed beneath the "old" one and this epithelium
      displays an epidermal orthokeratinized phenotype, whereas the "old" epithelium
      remains unchanged. This phenomenon of "partial reversibility", as well as the
      mutually exclusive distribution of the markers of the two alternative routes of
      differentiation, demonstrate that retinoic acid is indeed able to provoke
      metaplasia of adult epidermal keratinocytes.

PMID- 7641979
TI  - Tissue-specific expression of the rat insulin 1 gene in vivo requires both the
      enhancer and promoter regions.
AB  - The tissue specificity conferred by cis-acting regulatory elements of the rat
      insulin 1 gene was examined in both cultured cells and transgenic mice. The
      enhancer region (-346/-103) coupled to a ubiquitous promoter activated expression
      of a reporter gene in insulinoma cells but not in fibroblasts, in agreement with
      our previous work, and the specific expression was limited to a subregion
      containing the FAR and FLAT elements (-252/-199). In transgenic mice, however,
      this FAR-FLAT minienhancer alone failed to activate a reporter gene. Under the
      same conditions, in vivo, the enhancer (-346/-103) activated gene expression, but
      did not confer complete pancreatic specificity. The transgene, in this case, was
      expressed in pancreas and also in brain. Reassociation of the rat insulin 1
      promoter (-102/+9) with the enhancer (-346/-103) prevented expression in brain
      and thus restored pancreatic specificity. All of these observations indicate that
      tissue-specific expression of the rat insulin 1 gene, in vivo, results from
      interaction of multiple sequence elements and not from any single minimal
      sequence.

PMID- 7641981
TI  - Immunocytochemistry of annulate lamellae: potential cell biological markers for
      studies of cell differentiation and pathology.
AB  - We have generated specific antibodies recognizing different proteins of the
      nuclear pore complex and have applied them for the biochemical and microscopical
      analysis of annulate lamellae (AL). Using the example of the Xenopus laevis
      oocyte we show that the combined application of such antibodies to different
      components of the nuclear pore complex allows the unequivocal identification of
      AL. We propose to use such antibodies in immunostaining light microscopy for
      detecting AL as a diagnostic marker in a diversity of cell types, including those
      with pathological alterations in AL frequency and distribution.

PMID- 7641982
TI  - [Mechanisms of nervous regulation of oxygen transport and consumption in ischemic
      heart disease].

PMID- 7641983
TI  - [Ecologic and physiologic features of the adaptive reactions of the native and
      foreign populations of Evenki].

PMID- 7641984
TI  - [Effect of moderate high-altitude hypoxia on the structure of circadian rhythms
      of the acid-base status and gas composition of the blood].

PMID- 7641985
TI  - [Reactions of healthy people to marked fluctuations in the weather and magnetic
      storms].

PMID- 7641986
TI  - [Critical frequency of light flickers and alteration of motor skills].

PMID- 7641987
TI  - [Functional state of monocytes as an index of human adaptation].

PMID- 7641988
TI  - [Duration of gastric emptying and intestinal transit in people with varying
      levels of motor activity].

PMID- 7641989
TI  - [Cerebral blood flow in newborn children].

PMID- 7641990
TI  - [Effect of acoustic feedback on the accuracy of voice imitation of signal
      duration].

PMID- 7641991
TI  - [Effect of diving and length of breathing delay on the morphologic composition of
      the blood in athletes].

PMID- 7641992
TI  - [Ovarian insufficiency in chronic nonspecific salpingo-oophoritis].

PMID- 7641993
TI  - [Visual evoked potentials in the frontal region of the left hemisphere during
      monotonous work at the display terminal].

PMID- 7641994
TI  - [Structure of correlations between reaction time to tones and the magnitude of
      EEG spectral density: sex-related differences].

PMID- 7641995
TI  - [Genetic correlations between human psychophysiologic characteristics. II. Evoked
      potentials and intellectual parameters].

PMID- 7641996
TI  - [Interhemispheric asymmetry of the resting EEG and its relationship to
      psychologic parameters of cognitive activity in families of schizophrenic
      patients].

PMID- 7641997
TI  - [Physiologic effects of photic stimulation and their relationship with subjective
      functional state characteristics].

PMID- 7641998
TI  - [Changes in cortical evoked potentials in alcoholism of varying degrees of
      severity].

PMID- 7641999
TI  - [The psychophysiologic basis for academic achievement].

PMID- 7642000
TI  - [Accuracy of maintenance of the position of projection of the overall center of
      mass of a person during standing].

PMID- 7642001
TI  - [Effect of postural tonic reflexes on the activity of the deltoid muscles in
      man].

PMID- 7642002
TI  - [Physiologic mechanisms of functional reserve mobilization in man during
      strenuous muscle activity].

PMID- 7642003
TI  - [Cross-correlation autonomic criteria of emotional stress].

PMID- 7642004
TI  - [Use of parameters of heart rate and hemodynamics for automated evaluation of the
      functional state of the body and effectiveness of its correction in industrial
      workers].

PMID- 7642005
TI  - [Short-term survival after heart transplantation: the relationships between
      preoperative hemodynamics, organ function and postoperative clinical events].
AB  - AIM OF THE STUDY: Pulmonary hypertension is known to affect prognosis of cardiac
      allograft recipients. Aim of this study is to elucidate the mechanisms relating
      preoperative hemodynamics to early post-transplant mortality. METHODS:
      Hemodynamic and pre- and postoperative clinical data of 122 heart transplant
      recipients were reviewed with respect to early mortality (within 1 month or in
      hospital). The relationships between hemodynamics and mortality were studied by
      means of univariate and multivariate analysis of absolute data and at different
      cut-off values of hemodynamic parameters. RESULTS: The following hemodynamic
      parameters were significantly different between survivors (n = 107) and non
      survivors (n = 15): right atrial pressure (7.7 +/- 4.7 vs. 12.1 +/- 8.6 mm Hg, p
      < 0.004), pulmonary vascular resistance (2.57 +/- 1.44 vs. 3.72 +/- 1.88 Wood
      units, p < 0.007), pulmonary vascular resistance index (4.43 +/- 2.53 vs. 6.53 +/
      3.28 Wood units x m2, p < 0.005), and transpulmonary gradient (8.8 +/- 4.8 vs.
      12.3 +/- 6.4 mm Hg, p < 0.02). Right atrial pressure and pulmonary vascular
      resistance index showed an independent value at stepwise multiple logistic
      regression analysis (p < 0.008 and < 0.03 respectively). When mortality was
      tested using cut-off values, it was significantly higher with right atrial
      pressure > or = 12 (7/28 vs 8/94, p < 0.05), pulmonary vascular resistance index
      > or = 8 (6/13 vs 9/109, p < 0.0005), and transpulmonary gradient > or = 15 (5/13
      vs 10/109, p < 0.01). High right atrial pressure, pulmonary vascular resistance
      index, and transpulmonary gradient were associated with higher preoperative
      bilirubin (p < 0.03), which was significantly superior in non-survivors (1.44 +/-
      1.53 vs. 0.83 +/- 0.61 mg/dl, p < 0.02). Postoperatively, severe right
      ventricular failure, severe renal failure and infections within 1 month were all
      strongly associated with an increased mortality (p < 0.00003); they were more
      common in patients with high preoperative right filling pressure (9% vs. 43%, p <
      0.00002) and/or high pulmonary vascular resistance index (14% vs. 38%, p < 0.03),
      in those with high right atrial pressure (9% vs. 35%, p < 0.0009), and in those
      with high pulmonary vascular resistance index (17% vs. 58%, p < 0.002)
      respectively. Mortality after acute rejection within 1 month was significantly
      higher in patients with high preoperative right atrial pressure (8% vs. 57%, p <
      0.006). CONCLUSIONS: Besides pulmonary hypertension, elevated preoperative right
      filling pressure appears to indicate an increased risk of early death after
      transplantation; pre- and postoperative end-organ dysfunction and post-transplant
      complications are more common or more threatening in this setting.

PMID- 7642006
TI  - [What is the useful information provided by a study of heart rate variability in
      clinical practice?].

PMID- 7642007
TI  - [Transesophageal atrial stimulation in the oral treatment of supraventricular
      reciprocal paroxysmal tachycardia in infants].
AB  - INTRODUCTION: The aim of the study was the evaluation of the usefulness of
      transesophageal atrial pacing in predicting chronic oral treatment efficacy of
      symptomatic reciprocating supraventricular tachycardia in infants and in avoiding
      the risk of very dangerous recurrences at home. METHODS: We studied 13 infants
      (11 males, 2 females, mean age 43 +/- 31 days) with symptomatic reciprocating
      supraventricular tachycardia and no structural heart disease. All patients had
      chronic oral therapy, using the drug effective in acute i.v. somministration.
      Each patient was discharged when supraventricular tachycardia was not inducible
      with transesophageal atrial pacing after 5 half-lives of the drug used in chronic
      oral treatment. All patients, every 6 months, were retested with transesophageal
      atrial pacing alternatively during chronic oral therapy and after complete wash
      out. Oral therapy was stopped in each patient when supraventricular tachycardia
      was not inducible after the wash out. RESULTS: The number of oral treatments
      tested for each patient were 2 +/- 1 (range 1-5). The number of transesophageal
      studies performed for each patient were 4 +/- 2 (range 3-7). No patient had
      symptomatic episodes of supraventricular tachycardia or needed to change therapy
      during the follow-up. The oral treatment was stopped after the twelfth month of
      life in 8 patients and after the twenty-fourth in 2 others without recurrences.
      CONCLUSION: Transesophageal atrial pacing seems to be useful in predicting
      accurately and rapidly the oral treatment efficacy of supraventricular
      tachycardia in infants. Our protocol seems to be effective to avoid dangerous
      recurrences of tachycardia and to decide when we can stop therapy without risk.

PMID- 7642008
TI  - [Biostatistics and clinical epidemiology. 1. The introductory concepts].

PMID- 7642009
TI  - [An echocardiographic study of left ventricular diastolic function in patients
      with diabetes mellitus type 2].
AB  - AIM OF THE STUDY: To evaluate left ventricular diastolic function by Doppler
      echocardiography in patients with type 2 (non-insulin-dependent) diabetes
      mellitus, without coronary artery disease. BACKGROUND: Previous studies suggest
      that the velocity curve obtained by Doppler echocardiography of the mitral inflow
      may reflect the filling pattern of the left ventricle. METHODS AND RESULTS: To
      evaluate the presence of diastolic impairment of the left ventricle in diabetic
      patients without evidence of coronary artery disease, 30 patients with non
      insulin-dependent diabetes mellitus and 20 normal control subjects underwent M
      mode, two-dimensional (2-D) and Doppler echocardiography. In the group of
      diabetic patients (Diabetics), the peak E wave velocity was 0.70 +/- 0.11 m/sec,
      while in the control group (Controls) it was 1.1 +/- 0.23 m/sec (mean values,
      +SD, p < 0.001). The peak A wave velocity was 0.89 +/- 0.17 in Diabetics, versus
      0.60 +/- 0.34 in Controls. Consequently, E/A ratio was 0.81 +/- 0.18 in
      Diabetics, versus 1.73 +/- 0.29 in Controls (p < 0.001). Isovolumic relaxation
      time was 0.08 +/- 0.021 sec in Diabetics, while in Controls it was 0.04 +/- 0.02
      sec (p < 0.001). Left atrium diameter was 41 +/- 11 mm in Diabetics, and 37 +/- 4
      mm in Controls (p = NS). Left ventricular volumes, ejection fraction,
      interventricular septal and posterior wall thickness were similar in both groups.
      No correlation was found between diabetes duration and diastolic function
      indexes. In Diabetics no correlation was found between age and E/A ratio
      (correlation coefficient +/- 0.11) while in Controls E/A ratio was lower in the
      older subjects (r = +/- 0.75). This ratio was 1.89 +/- 0.20 in Controls aged < 65
      years, and 1.6 +/- 0.33 in Controls aged > or = 65 years. (p = 0.06). These data
      suggest that 1) E/A ratio and isovolumic relaxation time are significantly
      altered in non-insulin-dependent diabetic patients without coronary artery
      disease; 2) Doppler echocardiography is a useful technique to detect left
      ventricular diastolic impairment; 3) diastolic impairment seems not to correlate
      with disease duration; 4) systolic function is normal in our group of type 2
      diabetic patients.

PMID- 7642010
TI  - [Transesophageal echocardiography in patients free of carotid disease with an
      ischemic stroke].
AB  - BACKGROUND: Cardioembolism is the cause of cerebral infarct in 15 to 30% of
      cases. The aim of the present work is to detect, by transesophageal
      echocardiography (TEE), potential cardioembolic sources in patients with cerebral
      ischemia without atherosclerotic carotid disease at duplex carotid ultrasound
      examination. METHODS: From 1991 onwards, 420 consecutive patients who presented
      with cerebral ischemia, detected by computerized axial tomography, underwent an
      echotomography examination of the cerebral afferent vessels and a transthoracic
      echocardiogram (TTE). Three hundred and thirty out of these patients were
      excluded since they had carotid plaques; of the remaining 90, 80 (mean age 61.6
      years range: 25-86, 50 males and 30 females) underwent a transesophageal
      examination. The patients were studied with an HP Sonos 1000 system with 2.5 and
      3.5 MHz frequency probes for TTE; 7.5 and 5 MHz probes were used for
      echotomography and TEE respectively. RESULTS: The TEE identified cardioembolic
      sources in 81% of the cases, versus 46.2% using TTE (p < 0.0001) with a
      significant statistical difference for thrombus, spontaneous echo contrast and
      paradoxic shunt (p < 0.0001). When the patients with cerebral ischemic events
      (group A) were compared with the 156 cardiac patients (group B) (mean age: 59.7,
      range: 19-86, 92 males and 64 females), without ischemic events, group A showed a
      significant higher prevalence of thrombus, spontaneous echo contrast,
      calcification of the mitral anulus, interatrial aneurysm and paradoxic shunt.
      CONCLUSIONS: Our experience confirms that TEE is very useful and more sensitive
      than TTE for diagnosing cardioembolic sources; so, this new diagnostic tool
      should become a useful part of the diagnostic iter for patients with ischemic
      stroke and normal carotid vessels. The prevalence of some heart conditions in the
      stroke group poses the problem of whether to advise anticoagulant or antiplatelet
      therapy and, in selected cases, a surgical approach. The absence of heart and
      vascular conditions in the extracranial regions of patients who have had a
      cerebral stroke, suggests an intracranial condition and the problem of performing
      an angiographic examination arises.

PMID- 7642011
TI  - [Changes in the compliance of the radial artery in normotensive subjects with
      familial hypercholesterolemia].
AB  - BACKGROUND: Recent studies have shown that in normotensive hypercholesterolemic
      subjects endothelial dependent dilatation of arterioles is impaired. METHODS: We
      studied the effects of hypercholesterolemia on arterial compliance in
      normotensive subjects of both sexes, with a normal serum cholesterol (n = 8,
      total serum cholesterol = 209 +/- 7 mg/dl, means +/- SEM), an elevated serum
      cholesterol (n = 8, 285 +/- 8 mg/dl) and familial hypercholesterolemia (n = 8,
      393 +/- 20 mg/dl). All subjects were normotensive and devoid of clinical and
      laboratory evidence of atherosclerotic lesions. The mean age of the 3 groups was
      46.7 +/- 2.5, 51.5 +/- 2.9 and 49.8 +/- 2.9 years respectively. In
      hypercholesterolemic subjects use of hypolipidemic drugs was stopped 2 months
      before the study. Arterial compliance was measured from the radial artery by an
      echo-tracking device capable of providing radial artery diameter and, with the
      addition of a Finapres device, diameter/pressure and compliance/pressure curves
      continuously over the systolic-diastolic blood pressure range. RESULTS: Mean
      arterial pressure was similar in the three groups (84.5 +/- 6.1, 79.8 +/- 2.4 and
      73.1 +/- 4.4 mm Hg). Arterial compliance was similar in normocholesterolemic and
      non familial hypercholesterolemic subjects but it was strikingly reduced (50%) in
      familial hypercholesterolemic subjects. The reduction was even more evident
      following prolonged local ischemia because while in the first two groups arterial
      compliance increased after ischemia, in familial hypercholesterolemia no increase
      occurred. CONCLUSIONS: Thus, familial hypercholesterolemia is accompanied by a
      striking CONCLUSIONS: Thus, familial hypercholesterolemia is accompanied by a
      striking reduction in radial artery compliance, i.e. a marked increase in
      arterial wall stiffness. This may increase the traumatic effect of blood pressure
      on the arterial wall, favouring atherosclerosis. The lack of compliance
      alterations in non familial hypercholesterolemia suggests that this hemodynamic
      disturbance either occurs when serum cholesterol is more markedly increased or it
      has a genetic origin.

PMID- 7642012
TI  - [A comparison between flecainide and sotalol in the prevention of recurrences of
      paroxysmal atrial fibrillation].
AB  - OBJECTIVES: Aim of the present study was to assess the efficacy and safety of
      flecainide (F) and sotalol (S) for the prevention of recurrences of paroxysmal
      atrial fibrillation (PAF). METHODS: Sixty-six patients with PAF (> or = 3
      episodes of atrial fibrillation in the last year) in sinus rhythm, were
      randomized to pharmacological oral treatment with F (20 patients-Group A), with S
      (20 patients-Group B) and placebo (P) (26 patients-Group C). During the follow-up
      (one year duration) were evaluated on I, III, VI and XII months the number and
      tolerance of the atrial fibrillation recurrences, cardiac and/or noncardiac side
      effects. The patients with more than two recurrences in the same follow-up
      interval withdrew from the study. In each patient 14 clinical and laboratory
      variables were evaluated. RESULTS: After 12 months were arrhythmia-free
      respectively 70% of Group A patients, 60% of Group B patients, 27% of Group C
      patients. Univariate analysis showed that treatment with F was related to
      decrease of atrial fibrillation recurrences (one recurrence 67%, two recurrences
      81%, three recurrences 81%), treatment with S was related to decrease of
      recurrences (two recurrences 59%); the variable most significantly related to the
      risk of arrhythmia recurrence is the higher value of basal cardiac rate (one
      recurrence t = 2.15, two t = 2.22, three t = 2.96, four t = 2.06). There was not
      statistically significant difference in maintenance of sinus rhythm at the end of
      the follow-up between the groups of patients on F and S (p = 0.163); treatment
      efficacy was significantly higher than P (p = 0.002). Multivariate analysis
      showed that treatment with F and S decreases the risk of arrhythmia recurrence
      respectively of 85% and 76% versus placebo at the end of the follow-up. The
      incidence of cardiac and/or noncardiac side effects was not clinically
      significant. CONCLUSION: F and S are both effective and safe for prevention of
      PAF, with 70% and 60% respectively of patients arrhythmia-free after 12 months of
      treatment. Side effects were common, but clinically significant adverse events
      were uncommon. A higher value of basal cardiac rate was predictive of atrial
      fibrillation recurrences in the patients during treatment.

PMID- 7642013
TI  - [The MELAS syndrome and dilated-hypertrophic cardiomyopathy: a case report].
AB  - We describe a case of a 34-year-old male patient first hospitalized in February
      '93 for stroke (concomitant dilated-hypertrophic cardiomyopathy was noted), and
      then in April '93 for congestive heart failure. The presence of myopathy,
      encephalopathy, lactic acidosis and stroke episode allows for the diagnosis of
      MELAS syndrome, proven by a specific point mutation in mitochondrial DNA. In this
      case we were able to observe not only the electrocardiographic and
      echocardiographic features of hypertrophic cardiomyopathy, previously described
      in mitochondrial encephalomyopathies, but we were also able to monitor the rapid
      evolution of this cardiomyopathy towards the hypokinetic dilated form with severe
      impairment of systolic function; this transition was due to changes in the heart
      anatomy and structure with reduction in the left ventricular (LV) wall thickness
      and dilatation of all chambers. The remodeling of LV geometry seems to be not
      definite and capable of dynamic evolution, as suggested by clinical and
      echocardiographic findings evaluated six months after the hospitalization. In
      this patient, we obtained a mid-term favourable clinical outcome using inotropic
      drugs and Ubiquinone (coenzyme Q), an intermediate substrate of the energetic
      metabolism, which seems to be poorly synthetized because of the early enzymatic
      defects in the mitochondrial respiratory chain.

PMID- 7642015
TI  - [The Eisenmenger syndrome. Is it still a problem for the cardiologist in
      adults?].

PMID- 7642014
TI  - [The predictive value for major arrhythmic events of ventricular arrhythmias,
      particularly nonsustained ventricular tachycardias, in the subacute phase of a
      fibrinolyzed infarct. An analysis of GISSI-2 data. Gruppo Italiano per lo Studio
      della Streptochinasi nell'Infarto Miocardico].
AB  - BACKGROUND: The relationship between ventricular arrhythmias (VA) in the subacute
      phase of a myocardial infarction (MI) and subsequent major arrhythmic events,
      i.e. sustained ventricular tachycardia (SVT) and sudden death (SD), is well
      known. The importance of left ventricular dysfunction in the same context is also
      well established. The vast majority of the data in the literature come from the
      prefibrinolytic era and/or are derived from limited data bases. MATERIALS,
      METHODS AND RESULTS: We examined the large, uniform GISSI-2 population of acute
      fibrinolysed myocardial infarctions in order to evaluate the significance and
      predictive power of VA detected by Holter monitoring during the subacute phase.
      Particular attention was paid to the occurrence of nonsustained ventricular
      tachycardias (NSVT) since their role is still uncertain, so it is hard to assess
      the utility of invasive measures such as programmed electrical stimulation (PES).
      Left ventricular function was evaluated by mono-, and two-dimensional
      echocardiography. Holter monitoring was available in 8,676 patients; a six-month
      follow-up, as regards mortality was completed in 8,552 patients (98.5%) and, as
      regards SVT incidence, in 7.713 (88.9%). During the follow-up 256 patients died
      (3%), 84 out of them suddenly (1%). Twenty-six [corrected] patients out of 7,713
      (0.3%) experienced one or more SVT. The relationship between VA, left ventricular
      dysfunction and major arrhythmic events was evaluated by odds ratios (OR) and
      their confidence intervals (CI). Odds ratios for the combined end-point (SD
      and/or SVT) was 4.49 (CI 95% 2.69-7.51) if the Holter showed > 10 VEB/hour; 2.34
      (CI 1.48-3.68) if couplets were present; 3.26 (1.52-6.99) if NSVT were present;
      3.02 (2.02-4.50) if any complex ventricular arrhythmia was detected. Left
      ventricular disfunction seemed to exert a more powerful influence: OR 9.80 (CI
      5.75-16.69) for SD and/or SVT. Any arrhythmic parameter had very low positive (<
      or = 3%) and very high (approximately 99%) negative predictive power.
      Multivariate analysis (Cox Model) including major prognostic factors confirmed
      the independent prognostic value of frequent VA (RR 2.75; 95% CI 1.58-4.79),
      couplets (RR 1.91; CI 1.28-2.86); complex VA (RR 2.02; CI 1.36-3.00). NSVT, after
      adjusting for the selected risk factors, was not independently associated with a
      worse prognosis. CONCLUSIONS: Ventricular arrhythmias detected by Holter
      monitoring during the subacute phase of a MI still have prognostic significance
      for major arrhythmic events in the fibrinolytic era. The presence of NSVT triples
      the risk of SD and/or SVT in the six months after an acute MI, but loses any
      predictive power in a multivariate analysis. Only 6.6% of the patients showed one
      or more episodes of NSVT in the Holter recording. If the ongoing clinical trials,
      MUSTT and MADIT, will confirm the usefulness of PES in such patients, the benefit
      will be confirmed to a very small proportion of the patients at risk of specific
      diagnostic tests. The positive predictive power of VA is very low and it is
      therefore mandatory to add other non-invasive variables to the screening to
      identify the subgroups at greatest risk. On the other hand the very high (99%)
      negative predictive power of VA and left ventricular dysfunction enables us to
      identify a large population of infarcts with a negligible risk, who need no
      further sophisticated investigations. From the point of view of the cost/benefit
      evaluation this seems to be an outstanding result.

PMID- 7642016
TI  - [The cardiologist and the law: legal problems in clinical practice].

PMID- 7642017
TI  - [Out-of-hospital cardiac arrest in an experimental model of the management of
      cardiologic emergencies in a metropolitan area].
AB  - Since March 1992, an emergency medical system--EMS--(Servizio Emergenze
      Cardiologiche Territoriale, SECT) operates in the metropolitan area of Turin
      (130, 16 Km2), for a population of 964,000 inhabitants. SECT is based on a mobile
      intensive care unit, staffed with a physician and a nurse, trained in advanced
      cardiopulmonary resuscitation (CPR) and equipped to treat all cardiac
      emergencies. According to the "Utstein Style" we report the demographic and
      clinical features of the patients (pts) suffering Cardiac Arrest (CA) and the
      impact of SECT on out-of-hospital CA. During 26 months of activity, SECT
      performed 3,648 missions (most important among these: 457 acute myocardial
      infarction, 723 angina, 523 arrhythmias, 270 acute heart failure, 154 cardiac
      arrest), and managed 207 confirmed CA (154 calls for CA, 53 CA occurred after
      team arrival because of other symptoms). Resuscitation was attempted in 135 pts,
      in 72 pts medical personnel accerted an irreversible death state. 86% of CA
      occurred at home. In all cases a cardiac etiology was presumed. All CA were
      witnessed: 53 by EMS personnel, 82 by lay bystander. In 53 EMS witnessed CA,
      ventricular tachycardia (VT) or ventricular fibrillation (VF) was showed in
      47.2%, asystole in 43.4%, other rhythms (Oth) in 9.4%. Return of spontaneous
      circulation (ROSC) was obtained in 52.8% pts, 76% in VT/VF Group. 43.4% were
      admitted alive to intensive care unit (ICU), 68% in VT/VF Group. 37.7% were
      discharged alive, 64% in VT/VF Group. In 82 lay witnessed CA initial rhythm was
      VT/VF in 31.7%, asystole in 59.7%, Oth. In 8.6%. CPR was attempted by lay
      bystander in 28% of cases. ROSC was obtained in 18.3%. CPR was attempted by lay
      bystander in 28% of cases. ROSC was obtained in 18.3% pts, 42.3% in VT/VF Group.
      15.8% were admitted alive to ICU, 34.6% in VT/VF Group. 9.7% pts were discharged
      alive, 23% in VT/VF Group. Discharged alive rate in lay attempted CPR cases was
      17.4%. The collapse-EMS CPR interval was 16 +/- 6.13 min (range 4-29), with a
      collapse-call receipt interval of 8.57 +/- 5.75 min (range 1-23) and a call
      receipt-EMS CPR interval of 8.06 +/- 3.56 min (range 2-19). The same intervals
      are significantly longer in not attempted CPR cases: respectively 26.53 +/- 10.73
      min (range 10-65) -p < 0.001-, 19.29 +/- 11.3 min (range 5-60) -p < 0.001- and
      8.26 +/- 3.96 (range 3-25) -p = NS-. Although far from the international
      effectiveness standards, SECT seemed to improve the out-of-hospital CA prognosis.
      High rate of CA occurred at home, time delay in early access link, better trend
      in survival in lay bystander attempted CPR cases and lack in early defibrillation
      lead to strategies for system improvement through targeted CPR training as well
      as semiautomatic external defibrillators introduction.

PMID- 7642018
TI  - [Pulmonary valvuloplasty in childhood: the immediate results and long-term follow
      up].
AB  - BACKGROUND: Pulmonary balloon valvuloplasty is the treatment of choice of
      pulmonary valve stenosis, but early results and long-term follow-up in a numerous
      and homogeneous pediatric population are poorly known. MATERIAL AND METHODS: From
      April 1984 to April 1994, 202 valvuloplastic procedures were performed in 197
      patients (age 52.5 +/- 150 months). Hemodynamic data were analysed according with
      valvular morphology and patient's age at procedure. During a follow-up period of
      50 +/- 38 months, clinical and instrumental data were collected. RESULTS: After
      pulmonary valvuloplasty RV pressure decreased from 86 +/- 28 to 41 +/- 21 mm Hg
      (p < 0.001), transvalvular pressure gradient from 67 +/- 27 to 24 +/- 14 mm Hg (p
      < 0.001) and RV/LV pressure ratio from 1.01 +/- 0.29 to 0.53 +/- 0.19 (p <
      0.001). Overall success rate was 95% (187/197 patients). Pulmonary valve
      dysplasia and/or annulus hypoplasia significantly influenced the efficacy of the
      procedure and/or the recurrence of valvar stenosis (18.8% vs 2.7%, p < 0.01).
      During the follow-up period, clinical examination was unremarkable, and
      transvalvular pressure gradient did not change (23 +/- 9 vs 24 +/- 6 mm Hg at
      discharge, p = NS). Freedom from restenosis was 98% at 3 years and 96% at 5 and
      10 years. CONCLUSIONS: Pulmonary balloon valvuloplasty is a safe, effective and
      possibly definitive treatment for isolated pulmonary valve stenosis in infants
      and children. Age at valvuloplasty does not influence the success of the
      procedure, as opposed to valvular dysplasia and/or annulus hypoplasia that
      positively relate to the need of surgical valvotomy and/or the recurrence of
      stenosis during a long-term follow-up. In conclusion, prognosis of the majority
      of infants and children after a successful valvuloplasty is excellent during a
      long-term follow-up period.

PMID- 7642019
TI  - [Idiopathic ventricular fibrillation: from a collection of clinical cases to a
      prospective evaluation. The U-CARE Steering Committee. Unexplained Cardiac Arrest
      Registry of Europe].
AB  - BACKGROUND: The primary aim of U-CARE (Unexplained Cardiac Arrest Registry of
      Europe) is to collect clinical information on survivors about a documented
      episode of idiopathic ventricular fibrillation (IVF) and to follow these patients
      (pts) prospectively to acquire information on 1) recurrence of malignant
      arrhythmias or cardiac arrest, 2) development of a previously non obvious organic
      heart disease, 3) potential difference in outcome in pts treated with different
      drugs or devices. METHODS AND RESULTS: Within April 15th, 1994, eighty-six pts
      have been enrolled, 65 males and 21 females. The mean age at the time of the
      first cardiac arrest was 35 +/- 15 years. Clinical evaluation revealed "minor"
      functional or anatomical abnormalities in 14 subjects and they were excluded from
      the analysis. In the remaining 72 pts, no abnormalities were found at
      echocardiogram, Holter, angiography, exercise stress test. At the
      electrophysiologic study 35/68 pts were inducible. Thirty-eight pts received
      pharmacologic therapy, 28 an implantable defibrillator (ICD), three pts received
      both an ICD and drug therapy and three were left untreated. Follow-up data are
      available for 37 pts with a mean follow-up of 4.4 +/- 2.6 years. No patient had
      evidence of structural heart disease. Twenty-three pts remained asymptomatic, 12
      (32%) had a recurrence of syncope or cardiac arrest: three died suddenly and 2
      were defibrillated by the ICD. This study that represents the largest experience
      in IVF, shows: 1) all patients remained free from any organic heart disease at
      follow-up, 2) they have a high risk of recurrence of major arrhythmic events.
      CONCLUSIONS: An ICD implant would be appropriate in this population, at least
      until data on the efficacy of the pharmacologic therapy will be available.

PMID- 7642020
TI  - [The evolution of the therapeutic choice in patients with the outcomes of non-Q
      myocardial infarct: 2 periods compared].
AB  - BACKGROUND: Over the last years there has been a tremendous increase in coronary
      angioplasty procedures (PTCA), due to the availability of better materials and to
      the refinement of operators skill. It is not known however if this "PTCA boom"
      has modified our approach to the patients with particular clinical situations,
      such as those with non-Q wave myocardial infarction. The purpose of this study
      was to verify, in patients undergoing coronary angiography for clinical reasons
      after a non-Q wave myocardial infarction, the clinical decision concerning the
      therapeutical choice in two different periods (101 patients in 1988 vs. 102
      patients in 1992). METHODS AND RESULTS: Patients in the two groups had similar
      clinical manifestations whereas patients observed in 1992 had more frequently 2
      vessel disease than single vessel disease as compared to patients studied in 1988
      (p < 0.05). The distribution of patients with normal coronary arteries or with 3
      vessel disease was similar in the two periods. In 1988 medical therapy was the
      most recommended treatment at discharge (47%), followed by aorto-coronary bypass
      (29%) and coronary angioplasty (24%). On the contrary, in 1992 PTCA was performed
      in 48% of patients, medical therapy was recommended in 28% while the incidence of
      coronary surgery was reduced to 24% (p < 0.01). From a clinical point of view a
      significant increase in PTCA procedures was seen in patients presenting with
      unstable angina after the non-Q wave myocardial infarction (54% of these patients
      undergoing PTCA in 1992 vs. 30% in 1988, p = 0.03) and in patients with effort
      angina and a positive exercise test at low workload (53% of these patients
      undergoing PTCA in 1992 vs. 22% in 1988, p < 0.05). Moreover, in 1992 PTCA
      procedures increased in patients with single vessel disease (64% in 1992 vs. 49%
      in 1988) and in patients with 2-vessel disease (64% in 1992 vs. 9% in 1988).
      Therefore, in these patients the need of aorto-coronary by pass was reduced from
      39% in 1988 to 19% in 1992 (p < 0.05). The success rate of PTCA procedures was
      98% in 1992 and 83% in 1988. No major complications were observed in the two
      study periods and no patients underwent urgent coronary surgery. CONCLUSIONS:
      These data show an increase in PTCA procedures over the last years in patients
      undergoing coronary angiography for clinical reasons after a non-Q wave
      myocardial infarction. The greater experience of operators allowed for improved
      results, thus reducing the need of coronary surgery in these patients.

PMID- 7642021
TI  - [High-resolution electrocardiography in 102 young healthy subjects].
AB  - BACKGROUND: The aim of this study was to evaluate the normal values of the most
      common indexes used in the analysis of ventricular late potential in 102 young
      male subjects. METHODS: The recordings were performed by means of a Marquette
      electronics Hi-Resolution ECG Mac 15, with filters at 25-250 Hz, 40-250 Hz and 80
      250 Hz. The parameters obtained were: filtered QRS duration (QRSD), high
      frequency low-amplitude signals duration (HFLA), and the root mean square of the
      signal expressed in the terminal portion of QRS (RMS). The body surface was also
      evaluated. RESULTS: QRSD (121.23 ms-113.9 ms-99.9 ms); RMS (105 uV-42.77 uV-34.3
      uV); HFLA (17.5 ms-29.3 ms-29.3 ms). The comparison between our results and those
      proposed by other authors for normal subjects showed different results,
      particularly concerning the filtered QRS duration. We suppose that these
      discrepancies may be due to the different instrumentations used and to the
      different age and sex of the study population. CONCLUSIONS: From these results we
      confirm that a normal range for each index must be done for homogeneous groups of
      subjects for age and sex, in healthy subjects as well as for different heart
      disease.

PMID- 7642022
TI  - [SFAAT: the study of nonrheumatic chronic atrial fibrillation in the Trieste
      area. Results of an enrollment study].
AB  - BACKGROUND: Chronic atrial fibrillation unassociated with rheumatic valvular
      heart disease (NRAF) considerably increases the risk of thromboembolism. Recent
      studies have provided new evidence concerning the risk-benefit ratio of
      anticoagulant therapies in patients with AF. OBJECTIVE: To evaluate the incidence
      of primary end points (ischemic stroke, systemic embolism, bleeding complications
      to oral anticoagulant or antiplatelet therapy) and secondary end points (death,
      TIA) in patients with NRAF. METHODS AND RESULTS: Between November 1992 and June
      1993, 694 patients with chronic NRAF were enrolled in the Trieste Area Study on
      Nonrheumatic Atrial Fibrillation (TASAF), an ongoing prospective community study
      with a follow-up period of 2 years. The preliminary results of the enrolled study
      population show: an elevated mean age (71 +/- 9 years), the prevalence of males
      (383/694), high prevalence of overt or previous heart failure (23%), of mitral
      regurgitation confirmed at echocardiography (30%) and of previous myocardial
      infarction (11%). Many of the enrolled patients had a history of hypertension
      (58%). With regard to the etiology of the underlying heart disease, the following
      should be emphasized: a high incidence of cardiac hypertrophy (with or without
      history of hypertension) (28%) and of degenerative cardiopathy (20%);
      unclassifiable cardiopathy (14%); and lone AF (13%). Echocardiographic findings:
      left ventricular dysfunction (17%); mitral annular calcification (27%); and good
      mean left ventricular function (EF 0.50 +/- 0.15). Retrospectively there were 96
      clinically documented embolic events in 78 subjects while in 34 patients there
      were 38 episodes suspected for embolism or TIA. Nine patients suffered 1
      recurrence of embolism; three patients suffered 2 recurrences; one patient had 3
      recurrences; and 4 patients had one suspected recurrence of TIA. In 35 cases the
      embolic events clustered around the time of the onset of the arrhythmia. In the
      other 99 subjects the embolic complication appeared after the onset of AF: range
      1-266 months. The group of patients with true embolic events in comparison with
      patients without embolism or with suspected embolism or TIA had same variables
      predictive of thromboembolic complications: arrhythmia duration (p = 0.09) and
      previous myocardial infarction (p = 0.03); in contrast mitral annular
      calcification (p = 0.06), history of hypertension (p = 0.09) and cardiac
      hypertrophy (with or without hypertension) (p = 0.07) demonstrated only a slight
      trend of statistical significance. Comparing the clinical characteristics and
      echocardiographic findings of patients without embolism with those of patients
      with tru embolism, or suspected embolism, or TIA the variables predictive of
      thromboembolic events were: arrhythmia duration (p = 0.007), history of
      hypertension (p = 0.01), cardiac hypertrophy (with or without hypertension (p =
      0.02) and mitral annular calcification (p = 0.01), at the same time, age showed
      only a trend of statistical significance (p = 0.06). Among the 616 patients
      without a history of embolism only 3% were treated with oral anticoagulant agents
      and 28% with antiplatelet therapy, while among the 78 subjects with documented
      embolism only 28% were receiving anticoagulant therapy and 58% were receiving
      antiplatelet agents. CONCLUSIONS: NRAF is an important risk factor for
      thromboembolism. Some clinical characteristics and echocardiographic findings
      increase the risk. Physicians still hesitate to use oral anticoagulants and
      antiplatelet agents in their patients for the prevention of embolic
      complications.

PMID- 7642023
TI  - [The usefulness of transesophageal echocardiography in the follow-up of patients
      operated on for replacement of the ascending aorta with a tubular-valvular
      prosthesis (Cabrol's intervention)].
AB  - OBJECTIVES: The usefulness of transesophageal echocardiography (TEE) in assessing
      the postoperative results of aortic root replacement (Cabrol's procedure) was
      evaluated. METHODS: Between 1986 and 1993, 31 patients underwent replacement of
      the aortic valve and ascending aorta by a composite graft using the Cabrol
      procedure. Twenty-six patients had annuloaortic ectasia, two type I DeBakey
      dissection and four type II dissection. Hospital mortality was 9.7%. Studies were
      performed in 18 patients, two to 70 months (mean 27.5 months) after composite
      graft replacement. The following features were examined: prosthetic aortic valve
      function, coronary graft morphology and function, tubular graft and aneurysm
      wrapped around morphology and dimensions, presence of intimal flap, false lumen
      and thrombus in the false lumen and persistence of right atrial fistula. RESULTS:
      Periprosthetic leakage with significant regurgitation was detected by TEE in 3
      (16.6%) of 18 patients. In one patient with infected aortic graft a fistula
      between the periprosthetic space and the right ventricle was detected (confirmed
      at reoperation). In another patient occlusion of the graft for left coronary
      artery was noted. In three patients (16.6%) an aneurysm of the periprosthetic
      space with perivalvular leakage and persistence of the fistula with the right
      atrium was visualized. In the two patients operated for DeBakey type I dissection
      an intimal flap persisted distal to the graft and in one patient flow was
      detected in the false lumen, while it was totally obliterated in the other.
      CONCLUSIONS: 1) Complications after Cabrol's procedure are not infrequent;
      although the real importance of some of them (periprosthetic aneurysm,
      persistence of dissection) is uncertain, a careful follow-up may be essential to
      improve the long term survival. 2) TEE is a useful and well-tolerated procedure
      for postoperative follow-up of patients who underwent aortic root replacement
      with Cabrol's procedure.

PMID- 7642024
TI  - [The side effects and safety of the echo-dobutamine test. The experience with 373
      patients].
AB  - BACKGROUND: A potential limitation to the clinical utilization of dobutamine
      stress echocardiography is the higher incidence of side effects in respect to
      other noninvasive tests for the diagnosis of coronary artery disease reported by
      some authors. Due to the increased utilization of this test for the evaluation of
      chest pain and for prognostic stratification in patients with a recent myocardial
      infarction, we analyzed the results of 373 consecutive tests to evaluate the
      incidence and clinical significance of side effects induced by dobutamine.
      METHODS: Dobutamine stress echocardiography was performed in 256 patients (69%)
      for the evaluation of chest pain; 85 out of 256 (33%) suffered from a previous
      myocardial infarction. 117 patients (31%) were studied in the early phase after
      an acute myocardial infarction for prognostic purposes. Dobutamine was infused
      starting with the dose of 5 gamma/kg/min over 3 minutes with incremental steps of
      10-20-30-40 gamma/kg/min over 3 minutes under 2D-echocardiographic and 12-lead
      electrocardiographic monitoring. RESULTS: In 95% of cases the test was stopped at
      the achievement of a target end point: wall motion abnormalities (60%),
      significant ECG changes (5%), 85% of the age-predicted maximal heart rate (13%),
      maximal dose (17%); only in 5% of cases a limiting side effect requiring a
      premature interruption of the test occurred: hypertension (systolic blood
      pressure over 240 mm Hg and/or diastolic over 120 mm Hg) (2%); symptomatic
      hypotension (0.5%); severe chest pain (1%); nausea (0.5%); cardiac arrhythmias
      (1%). Cardiac arrhythmias were the most frequently registered non limiting side
      effect. During the test 79 episodes of supraventricular arrhythmias and 211
      episodes of ventricular arrhythmias occurred. Supraventricular arrhythmias
      consisted usually of benign sporadic premature beats; only 3 cases of self
      limiting supraventricular tachycardia or atrial fibrillation were recorded.
      Sporadic ventricular premature beats were the most frequently recorded
      arrhythmias; 10 patients developed a ventricular tachycardia; however in no case
      this arrhythmia was sustained, associated with subjective symptoms and required
      the administration of a specific antiarrhythmic drug or the premature
      interruption of the test. Patients were divided according to the absence (Group
      1, G1, n = 193, 52%) or the presence (Group 2, G2, n = 180, 48%) of cardiac
      arrhythmias during the test. Patients of G2 differed from patients of G1 only in
      respect of the maximal dose of dobutamine infused (33.5 vs 28.6 gamma/kg/min, p <
      0.0005) and the incidence of a wall motion abnormality in the basal
      echocardiogram (66% vs 53%, p < .01). The second most recorded non limiting side
      effect (71/373 pts) (19%) was the occurrence of systolic hypotension, a drop of
      systolic blood pressure > or = 20 mm Hg in respect of the antecedent infusion
      step. In all cases no symptoms developed and the great majority of patients with
      this finding had a normal echocardiographic response to dobutamine at the time of
      his occurrence. CONCLUSIONS: Dobutamine echo stress test is limited by the
      occurrence of significant side effects only in a minority of patients (5%);
      however in all cases, including complex ventricular arrhythmias, these side
      effects were self limiting and promptly recovered after interruption of the drug
      infusion. Non limiting side effects, in particular cardiac arrhythmias and
      systolic hypotension, are usually well tolerated and not associated with the
      occurrence of myocardial ischemia or left ventricular disfunction; thus,
      dobutamine echo stress test may be considered a safe test for the evaluation of
      the presence and severity of coronary artery disease both in patients with a
      previous or recent myocardial infarction and in patients without myocardial
      infarction.

PMID- 7642025
TI  - [Ventricular tachycardia secondary to myocardial contusion in an athlete: a
      clinical case report].
AB  - A 22-year-old athlete complained of palpitations shortly after a chest trauma
      during a basket competition. His electrocardiogram showed a ventricular
      tachycardia of 250 beats per minute, reverted to sinus rhythm with a chest thump.
      Standard electrocardiogram was normal. The following days he had an enzymatic
      pattern consistent with acute myocardial infarction, and the echocardiogram
      evidentiated an apical hypokinesia with a mural thrombosis. The patient recovered
      completely; and 15 days after the acute event, a coronary arteriography and
      ventriculography did not revealed any abnormality.

PMID- 7642026
TI  - [Hyperinsulinism/insulin resistance: cause, effect or marker of essential
      arterial hypertension?].
AB  - Essential hypertension is often accompanied by metabolic abnormalities which
      commonly include hyperinsulinemia/insulin resistance. Even in the absence of
      these metabolic disorders, high blood pressure tends to be associated with
      insulin resistance. These observations raise two orders of questions: 1) whether
      hyperinsulinemia and insulin resistance are simply innocent bystanders or are
      causally involved in the initiation and/or promotion of hypertension; 2) whether
      blood pressure elevation is eventually caused by excess of insulin or whether it
      is a manifestation of the complex metabolic state responsible for insulin
      resistance. The purpose of this paper is to survey the clinical, epidemiological
      and experimental data that have led to the above generalizations and to address
      the potential significance of this coexistence. First, it could be argued that
      the relationship between high blood pressure and the associated metabolic defects
      is incidental. In this case, insulin resistance and hypertension may represent
      two independent consequences of a same metabolic disorder. On the other hand,
      there is evidence that suggests that insulin resistance (by itself or by insulin)
      may play a role in the etiology and/or the clinical course of hypertension.
      Although insulin has complex actions on the circulation (including a vasodilator
      effect), plausible mechanisms by which insulin might raise blood pressure include
      stimulation of the sympathetic nervous system, alteration of ion transport
      kinetics, increase of renal sodium retention and stimulation of vascular smooth
      cells growth. The pathways that could link insulin resistance, through
      hyperinsulinemia, with essential hypertension are based on the concept that a
      defect of insulin action on glucose utilization, does not imply that all other
      effects of insulin are equally blunted. However, in patients with insulinoma,
      hypertension has not been associated, and the acute administration of insulin
      does not cause an increase in blood pressure. It is also possible, on the
      contrary, that hypertension may be the cause of insulin resistance, but in
      various forms of secondary hypertension, impaired insulin sensitivity has not
      been found. It is probable that insulin resistance may represent, in a subgroup
      of individuals characterized by genetic predisposition (ethnicity, familiarity,
      etc.), simply a marker for susceptibility to hypertension. Hyperinsulinemia, in
      these subjects, may directly contribute to a raise in blood pressure by several
      mechanisms. In conclusion, despite the clinical importance of this association
      the nature of the relationship between insulin resistance and blood pressure
      remains obscure. Since hypertension does not develop in all insulin resistant
      subjects and hyperinsulinemia does not always cause a raise in blood pressure,
      the relationship must be modulated by other genetic or environmental factors.

PMID- 7642027
TI  - [The prognostic role of the stress test in patients discharged alive after an
      acute myocardial infarct. From thrombolytic studies prior to GISSI-2. Grupo
      Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico].

PMID- 7642028
TI  - [The inflammatory aspects in the initial phases of atherogenesis].
AB  - Inflammatory features have been found in various phases of the atherosclerotic
      process, from its inception-monocyte adhesion to the arterial endothelium-to its
      progression, up to the final steps of its clinical emergence. The present review
      re-examines recent elements of knowledge on the pathogenesis of the very early
      phases in atherosclerosis, highlighting how they may be described as an
      alteration of the endothelial adhesive properties towards circulating leukocytes,
      in a fashion similar to that occurring in acute inflammation. Such phenomena are
      referred to as "endothelial activation." The molecular mechanisms of such
      modifications are described, since they may presently offer a new target for
      interventional-especially preventive-strategies, in order to delay the onset of
      atherosclerosis.

PMID- 7642029
TI  - [About inflammation and atherosclerosis].

PMID- 7642030
TI  - [Myocardial scintigraphy and vital myocardium: which tracer is it preferable to
      use?].

PMID- 7642031
TI  - [A myocardial infarct with a depressed ST segment: is thrombolysis useful?].

PMID- 7642032
TI  - [Biostatistics and clinical epidemiology. 2. Evaluating a hypothesis].

PMID- 7642033
TI  - [Surgical revascularization in acute coronary insufficiency: an analysis of the
      risk factors for hospital mortality in urgencies and emergencies].
AB  - OBJECTIVES: A retrospective analysis of 444 patients (Pts) with acute coronary
      insufficiency (A.C.I.) submitted to coronary artery bypass grafting between
      January '85 and December '92 was performed in order to identify incremental risk
      factors associated with perioperative mortality and to evaluate whether
      prediction of mortality can be accomplished utilizing risk models specifically
      linked to the severity of myocardial ischemia. METHODS: Based on clinical and
      ECGraphic standpoints three different groups were identified: urgent group,
      comprehensive of 257 Pts. in whom, because of full medically controlled ischemia,
      myocardial revascularization could be delayed until to 24-48 hours. Emergency-A
      group, comprehensive of 127 Pts with recurrent ischemia despite medical therapy,
      but with no signs of coronary insufficiency at the time of institution of
      cardiopulmonary bypass (CPB). Emergency-B group, comprehensive of 60 Pts operated
      on after a mean preoperative ischemic interval of 3.9 +/- 2.4 hours who presented
      unrelenting signs of ischemia, either persisting since the inception of the
      clinical picture or lasting for over 30 minutes at the time of institution of
      CPB; among those, 27 Pts were in cardiogenic shock. RESULTS: Mortality rate in
      the three groups was respectively: 7.4%, 13.4%, 31.7%. Multivariate analysis
      identified the following risk factors of in-hospital mortality: urgent group:
      aortic cross-clamping time (A.C.C.T.) (p = 0.10) and ejection fraction (E.F.) (p
      = 0.023). Emergency-A group: A.C.C.T. (p = 0.017), E.F. (p = 0.023) and non-use
      of blood cardioplegia (B.C.) (p = 0.04). Emergency-B group: cardiogenic shock (p
      = 0.00), preoperative ischemic interval > 6 hours (p = 0.00), A.C.C.T. (p =
      0.018) and non-use of B.C. (p = 0.012). CONCLUSIONS: A useful stratification of
      Pts with A.C.I. in three different groups, each with its own risk model, can be
      obtained by means of clinical-ECGraphic criteria alone. Different prognostic
      weights can be attributed to the variables A.C.C.T., E.F. and non-use of B.C.
      depending on clinical status. A significant reduction of mortality rate in Pts
      with cardiogenic shock can be achieved by the utilization of individually
      tailored surgical management.

PMID- 7642034
TI  - [Familial pheochromocytoma: a family studied for 3 generations].
AB  - A family with a very high prevalence of pheochromocytoma (62%, i.e. 100% in the
      1st generation and 75% of the second one) is described. The proband was a 19-year
      old woman with a 30 g right-side tumor, who died at 24 years because of a heart
      failure. Both sisters of the proband developed a right-side pheochromocytoma at
      13 and respectively 14 years of age and are now normotensive after surgical
      exeresis. One of them had 3 sons: 2 with pheochromocytoma and a third one dead at
      9 years of age for pulmonary oedema. Accuracy is needed in studying relation of
      all subjects with pheochromocytoma.

PMID- 7642035
TI  - [Psychological, behavioral and occupational status changes after an aortocoronary
      bypass intervention].
AB  - BACKGROUND. Studies on the quality of life after coronary artery by-pass grafting
      (CABG) have yielded discordant results. Several studies have described
      psychological and social improvements while others have reported a lack of change
      in behavioural risk factors and return to work. There have been no reports on
      Italian patients, and, because of the wide range of psychological measures used
      in previous studies, it is difficult to draw any general conclusions. The aim of
      this study was to assess the psychological sequelae of CABG. METHODS. A total of
      164 patients (142 men and 22 women, aged 60 years) with myocardial ischemia,
      completed the CBA-H Questionnaire 3-5 days before elective CABG and again after 6
      months. RESULTS. State anxiety scores were lower after surgery (p < .000) as were
      health fears (p < .000), depression (p < .009) and life stress (p < or = .000)
      scores. There were also improvements in well-being (p < .003), affective
      relationships (p < .000) and sexual relations (p < .0007). There was a decline in
      behavioural risk factors, namely: smoking behaviour (p < .09), alcohol
      consumption (p < .002), over-eating (p < .0000) and sedentary life-style (p <
      .02). Clinical post-operative complications did not negatively influence
      patients' psychological state and return to work. Preoperative health fears (p <
      .04) and social anxiety (p < .02) did influence patients' return to work.
      CONCLUSIONS. In conclusion, psychosocial function, health state and quality of
      the life generally improved after elective CABG. Return to work was found to be
      an unreliable measure of the success of surgery. Pre- and post-operative data
      revealed a general denial trait which identifies patients at greater risk of
      cardiovascular events after CABG.

PMID- 7642036
TI  - Cardiac and vascular sources of peripheral thromboembolism in patients with
      atrial fibrillation. A combined transesophageal and vascular ultrasonographic
      study.
AB  - Atrial fibrillation is associated with an increased risk of peripheral
      thromboembolism. Although emboli arising from the left atrium are the most
      probable causes of peripheral ischemic events, coexistent vascular mechanisms may
      play a role in the genesis of thromboembolism. To assess the prevalence and the
      relative role of cardiac and vascular sources of thromboembolism in patients with
      atrial fibrillation 101 consecutive patients with (group 1: 47 patients) and
      without (group 2: 54 patients) recent thromboembolism were studied by
      transesophageal echocardiography and ultrasound duplex scanning of carotid
      arteries. Left atrial thrombosis was found in 19 (40%) group 1 patients and in 3
      (5%) group 2 patients. Left atrial thrombosis and/or spontaneous
      echocardiographic contrast were significantly more frequent in group 1 patients
      than in group 2 (70% vs 20%, p < 0.001). Stepwise regression analysis revealed
      that they were the only independent predictors of thromboembolism (p = 0.018, p =
      0.0003 respectively). Among clinical and transthoracic echocardiographic
      variables, left atrial diameter (p = 0.022), rheumatic mitral stenosis (p =
      0.0058) and absence of significant mitral regurgitation (p = 0.027) emerged as
      independent predictors of left atrial thrombosis and/or spontaneous
      echocardiographic contrast. When transesophageal parameters were also entered
      into the analysis, the only independent predictor was low blood flow velocity
      within the left atrial appendage (p = 0.0001). Vascular sources (obstructive
      carotid arteries plaques, non-obstructive ulcerated carotid plaques and thoracic
      aortic atherosclerotic debris) were found in 30.6% of patients. Their prevalence
      was not significantly different in the two groups (34% in group 1, 27% in group
      2). Vascular and cardiac sources coexisted in 23% of patients with
      thromboembolism. Seven of the 10 patients with more severe vascular lesions
      (i.e., obstructive carotid artery lesions or pedunculated mobile aortic debris)
      were from group 1 and 5 of them had negative cardiac results. In conclusion,
      these results indicate that a cardioembolic mechanism due to blood stasis within
      the left atrium is involved in most of the atrial fibrillation-related
      thromboembolic events. In patients with atrial fibrillation vascular sources are
      not infrequent and may be involved in the genesis of ischemic events in some
      patients. Transesophageal echocardiography may be useful in identifying subgroups
      of patients with atrial fibrillation who are at high thromboembolic risk.

PMID- 7642037
TI  - [Multiplane transesophageal echocardiography. The experience with 250 patients].
AB  - BACKGROUND AND OBJECTIVES: Multiplane transesophageal echocardiography provides
      countless tomographic planes through an angle of 180 degrees, thus overcoming the
      restriction encountered even with biplane transesophageal echocardiography.
      However, the incremental diagnostic value and clinical usefulness of this
      technique over biplane transesophageal echocardiography has not been extensively
      studied. STUDY POPULATION AND METHODS: In order to evaluate its advantages over
      biplane imaging, 250 patients (129 male, 121 females) aged 14-86 years, underwent
      multiplane transesophageal echocardiography. Indications for the study were the
      following: source of embolism in 83 patients, suspected prosthetic dysfunction in
      58 patients, valvular disease in 46 patients, congenital heart disease in 30
      patients, aortic disease in 17 patients, intra- or paracardiac masses in 11
      patients, and other reasons in 5. All the patients underwent an initial
      comprehensive diagnostic assessment using only the transverse (0 degree) and
      longitudinal (90 degrees) plane as the biplane imaging technique. "Off-axis"
      tomographic sections through the full 0 degree to 180 degrees angle were
      subsequently obtained by means of the gradual electrical rotation of the
      transducer. The echocardiographic information obtained by rotating the transducer
      was then compared to that obtained by biplane imaging to determine whether the
      additional information provided by "off-axis" sections a) carried diagnostic
      data; b) were to be considered useful but not diagnostic; or c) irrelevant.
      RESULTS: Additional diagnostic information was obtained in 24 out of the 250
      patients (9.6%), including the source of embolism in 9 patients, mitral
      insufficiency in 6 patients, bicuspid aorta in 2 patients, aortic endocarditis in
      2 patients, mitral prosthetic dysfunction in 4 patients and complex congenital
      heart disease in 1 patient. Additional useful but non-diagnostic information was
      obtained in 162 patients (64.8%). These data mainly allowed a more comprehensive
      assessment of the cardiac abnormality, enhancing confidence in the
      transesophageal diagnosis. Finally, data considered to be irrelevant were found
      in 64 patients (25.6%). CONCLUSIONS: The present study indicates that the wide
      range of tomographic planes provided by multiplane transesophageal
      echocardiography allows a more comprehensive evaluation of cardiac diseases and
      makes an accurate diagnosis possible in a significant number of cases.

PMID- 7642038
TI  - [The re-evaluation of the vasodepressive component in the carotid sinus
      syndrome].
AB  - BACKGROUND: The evaluation of the vasodepressor (VD) reflex of the carotid sinus
      syndrome is usually inaccurate, due to the difficulty in blood pressure
      measurement. AIM: To study the VD reflex with a beat-to-beat not invasive
      technique. METHODS: We investigated 68 patients (49 males, 19 females; mean age
      70 +/- 11 years) affected by carotid sinus syndrome: cardioinhibitory (CI) form
      was present in 47 patients, mixed (M) form in 10 patients and VD form in 11
      patients. The control group consisted of 9 patients (6 male, mean age 71 +/- 8
      years) affected by third degree atrioventricular block who had received the
      implant of a permanent pacemaker and were pacemaker-dependent with a prolonged
      asystole at time of temporary inhibition of the pacemaker itself. The study of
      the VD reflex was performed in the supine position; beat-to-beat arterial
      systolic pressure was monitored by a photoplethysmographic method using a finger
      cuff (Finapres technique). RESULTS: In all the patients the carotid sinus massage
      caused a marked fall in systolic blood pressure which was greatest at the end of
      the massage: from 143 +/- 25 mm Hg to 74 +/- 20 mm Hg in the patients with CI
      form, from 144 +/- 14 mm Hg to 76 +/- 18 mm Hg in those with M form and from 125
      +/- 26 mm Hg to 65 +/- 13 mm Hg in those with VD form. A decrease in systolic
      blood pressure > or = 50 mm Hg occurred in 84% of cases. Afterwards, the patients
      with CI form had a progressive increase of systolic blood pressure that reached
      the initial value after a mean of 27 seconds. In the patients with VD form
      systolic blood pressure was significantly (p < or = 0.5) lower than that observed
      in all the other groups, beginning from the third second after the end of the
      massage; mean systolic blood pressure value remained significantly lower than the
      initial value for more than 27 seconds. The patients with M form showed an
      intermediate pattern. Also control group patients showed a fall in systolic blood
      pressure immediately after pacemaker inhibition (from 152 +/- 29 mm Hg to 87 +/-
      25 mm Hg) that was of similar extent than that observed in carotid sinus syndrome
      patients, but pressure returned to initial value within 9 seconds. CONCLUSIONS:
      An important VD reflex is present in most patients with carotid sinus syndrome.
      It lasts more than the CI reflex and it persists for several seconds after the
      end of the massage. The initial fall of systolic blood pressure is of similar
      extent in all the forms of carotid sinus syndrome, but the patients with the VD
      form are characterized by a longer duration and greater entity of the decrease.
      These results point out the importance of the VD reflex in patients with the
      carotid sinus syndrome.

PMID- 7642039
TI  - [Reparative surgery of the mitral valve in bacterial endocarditis].
AB  - INTRODUCTION: Short and long-term results of valve repair for pure mitral
      insufficiency resulting from native valve endocarditis are reported in 28
      consecutive patients with a mean age of 55 years (range 18-74). METHODS: Six
      patients had acute endocarditis, with positive blood cultures in three of them.
      The mean time between onset of endocarditis symptoms and operation was 23 days in
      patients with acute endocarditis and 4.6 years in patients with healed
      endocarditis. Preoperatively, 87% of the patients were in NYHA class III.
      Indications for operation were heart failure (24 patients) and uncontrolled
      sepsis (4 patients). Mitral valvuloplasty was combined with other procedures in 4
      patients. There was previous underlying valve pathology in 75%. RESULTS: Mitral
      repair was performed according to the techniques proposed by Carpentier; in 2
      cases we used an original technique consisting of a double-orifice repair. Only
      one patient died in the hospital (operative mortality: 3.5%). By actuarial
      methods 96% of the patients were alive 6 years postoperatively. During the follow
      up period there was no recurrence of endocarditis and no reoperation for valvular
      insufficiency. Ninety-three per cent of the patients were in NYHA class I or II.
      CONCLUSIONS: We conclude that mitral valve repair for insufficiency resulting
      from bacterial endocarditis is possible in acute and healed disease, has a low
      operative mortality and has resulted in patients free of recurrent infection.
      Mitral valve repair is an attractive alternate to valve replacement in bacterial
      endocarditis.

PMID- 7642040
TI  - Concomitant myocardial infarction in identical twins with similar coronary
      lesions.
AB  - Two 42-year-old male twins were referred to our hospital for coronary angiography
      within 3 months. Despite some gross similarities in the aspect of the coronary
      tree, the coronary dominance pattern was not the same in these twins, but
      coronary lesions involved almost the same sites. Genetically determined local
      factors, such as the rheologic profile in some sections of the coronary tree, or
      the susceptibility to lipid deposition in some spots, may be important in the
      development of atheromatous lesions in special sites.

PMID- 7642041
TI  - [Acute ischemia in myocardial hypertrophy: a report of 2 clinical cases].
AB  - We report two cases presented with a clinical picture of acute myocardial
      ischemia, chest pain and giant negative T waves on electrocardiogram (absent in
      previous tracings). The echocardiogram B-Mode showed in both cases an asymmetric
      left ventricular hypertrophy caused, respectively, by hypertrophic cardiomyopathy
      and hypertensive heart disease. Short-term electrocardiographic evolution to
      complete normalization was observed in both cases. The echo-dipyridamole test did
      not show dissynergias and this fact suggested the absence of coronary artery
      disease; this hypothesis was confirmed by a normal coronary angiography. We
      suppose that in both patients a few factors contributed to the ischemic events:
      respectively an acute anemia due to gastric bleeding and high blood pressure
      values. This clinical presentation is an example of a difficult differential
      diagnostic problem between left ventricular hypertrophy and acute myocardial
      ischemia, as it shows that giant negative T waves in hypertrophic cardiomyopathy
      do not necessarily depend on left myocardial hypertrophy involving the apex or
      other segments but may be associated to an acute myocardial ischemia related or
      not to a coronary artery disease. A correct evaluation of these clinical cases is
      important for clinical, therapeutic and prognostic implications.

PMID- 7642042
TI  - [Atenolol i.v. in the acute phase of AMI: the indications, contraindications and
      interactions with thrombolytic drugs in the GISSI-2 study. The GISSI-2
      Researchers. Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto
      Miocardico].
AB  - BACKGROUND: In the pre-thrombolytic era, several studies showed the effectiveness
      of beta-blocker administration in the treatment of patients (pts) with acute
      Myocardial Infarction (MI). Results from the ISIS-1 and GISSI trials suggested
      that the combined administration of beta-blocker and of thrombolytic drugs in the
      acute phase of infarction could lead to a better prognosis. The possibility of
      synergic effects from the associated administration of these drugs was confirmed
      by small clinical trials. In GISSI-2 study a large number of patients treated
      with thrombolytic drugs were given i.v. atenolol (10 mg) as recommended therapy,
      not following a randomized study design. AIM: We reviewed the data of the GISSI-2
      study population in order to evaluate: 1) the number of pts treated with i.v.
      atenolol; 2) the anamnestic and clinical characteristics of treated und untreated
      pts; 3) the causes of exclusion from the beta-blocker therapy; 4) the causes of
      scheduled dose withdrawal and the incidence of side effects related to atenolol
      administration; 5) the interaction between atenolol and streptokinase (SK) and
      rtPA; 6) the incidence of relevant clinical events and the causes of death during
      the in-hospital period. RESULTS: Among 12377 evaluated pts, 5616 (45.4%) were
      given atenolol i.v., 2772 received SK (49.5%) and 2844 (50.5%) rtPA. Mean age was
      59.5 +/- 11.3 yrs in atenolol treated pts vs 63.4 +/- 10.9 yrs in untreated pts
      (p < 0.001); 34.1% of pts aged > 70 yrs vs 48.6% of younger pts (p < 0.00001) and
      42.1% of females vs 46.2% of males (p < 0.003) received atenolol. Pts with
      previous MI received less frequently atenolol than those without MI (17.5% vs
      13.5%, p < 0.00001). 88.5% of the treated pts was in Killip class I at entry
      (untreated 69.5%, p < 0.00001); anterior and lateral site, non-Q type and > or =
      5 electrocardiographic leads with ST segment elevation were more frequently found
      in atenolol treated pts, inferior and unknown site in untreated pts. Among 6761
      untreated pts, 32% did not receive atenolol for the occurrence of bradycardia,
      15.2% for hypotension, 14.1% for heart failure, 7.2% for bronchospasm or history
      of asthma, 6.2% for bradycardia and hypotension, 0.3% for death; in 25% of the
      untreated pts, none of the above-mentioned causes was detectable. 1064 pts
      (18.9%) did not complete the scheduled dose of atenolol for the occurrence of
      bradycardia or atrioventricular block > or = II degree (7.3%), hypotension (7%),
      bradycardia and hypotension (1.8%), heart failure (0.7%), death (0.03%), other
      causes (1.9%). Transient hypotension was found more frequently in pts treated
      with SK than in those receiving rtPA (9.3% vs 4.8%, p < 0.0001), but the rate of
      persistent hypotension was not different in both groups (4.6%). During the
      hospital phase a higher incidence of advanced atrioventricular block (12.3% vs
      4.3%), need of temporary or permanent pacing (5.6% vs 1.9%), sustained
      ventricular tachycardia (4.5% vs 2.8%), heart failure (12% vs 7.1%), ventricular
      fibrillation (8% vs 4.9%) and death (11.9% vs 5.1%) were shown in pts that were
      not given i.v. atenolol. Heart failure was the main cause of death in both groups
      (untreated 2.3% vs 2.2%); ventricular fibrillation (0.2% vs 0.48%), cardiac
      rupture (0.5% vs 1.4%), and electromechanical dissociation (0.9% vs 1.9%) were
      less frequent in treated pts. CONCLUSIONS: The absence of randomized design of
      atenolol administration limits the value of the differences found in the clinical
      outcome of the two groups of pts. In spite of that, the low incidence of death
      and side effects in treated pts, and the high percentage of pts who completed the
      scheduled dose of atenolol, confirm that the iv. administration of beta-blockers
      in the acute phase of the myocardial infarction is safe, well tolerated and
      suitable in almost an half of the patients submitted to thrombolytic therapy with
      SK or rtPA.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7642043
TI  - [Three-dimensional echocardiography. The technics and applications for the study
      of the left ventricle].

PMID- 7642044
TI  - [Pediatric cardiology at the threshold of the year 2000].

PMID- 7642045
TI  - [The transvenous implant of a pacemaker: the fastest way or the safest?].

PMID- 7642046
TI  - [Is an akinetic vital myocardium always recoverable after myocardial
      revascularization?].

PMID- 7642047
TI  - [Biostatistics and clinical epidemiology. 3. The analysis of categorized data].

PMID- 7642048
TI  - [Percutaneous mitral valvuloplasty: the immediate and long-term results].
AB  - BACKGROUND: Between December 1988 and December 1992, 235 patients (pts) underwent
      percutaneous balloon mitral valvuloplasty (PBMV). METHODS AND RESULTS: There were
      55 men (23%) aged 49 +/- 13 years and 180 women (77%) aged 51 +/- 13 years.
      Previous surgical commissurotomy (PSC) had been performed in 22 pts. Procedure
      was successful (area > 1.5 cm2 or area increase > or = 50% without mitral
      regurgitation > 2+) in 91.9% of pts, with increase in mitral valve area from 1.05
      +/- 0.2 to 2.26 +/- 0.6 cm2, decrease of transvalvular mean pressure gradient
      from 14.4 +/- 5.5 to 6.05 +/- 4.91 mm Hg and increase of cardiac index from 2.79
      +/- 0.75 to 3.17 +/- 0.9 l/m'/m2 (p < 0.001). Insufficient increase in valve area
      occurred in 3.8% of pts. Major complications included 5 pts with 3+ mitral
      regulation (MR) requiring mitral valve replacement (MVR), 2 TIA's (0.85%) and 1
      pericardiocentesis (0.42%). At follow-up (mean 18.9 months) clinical improvement
      was achieved in 93.8% of pts (NYHA class from 2.4 to 1.3); mitral valve area was
      1.9 +/- 0.4 cm2 and mean mitral valve gradient 5.3 +/- 2.3 mm Hg. Restenosis
      (area < 1.5 cm2 or > or = 50% loss of initial gain) occurred in 24 pts (10.16%).
      Six pts required MVR; 1 pt underwent a second successful PBMV. Multivariate study
      (logistic regression) identified as independent factors of severe MR NYHA class
      and PSC; echo score, age and basal mean mitral valve gradient were independent
      factors for restenosis. CONCLUSIONS: In conclusion, PBMV is a safe technique and
      stable clinical improvement can be obtained in the majority of pts.

PMID- 7642049
TI  - [Left ventricular remodelling at 3 months from a first transmural infarct: the
      effect of physical activity and of the patency of the necrotic artery on changes
      in volume and segmental kinetics].
AB  - OBJECTIVE: Aim of this perspective study was to assess in patients (pts) with a
      recent first transmural myocardial infarction (MI) the influence of a physical
      training, of MI location and of the patency of the infarct-related coronary
      artery on the modification of the left ventricle volumes and wall motion score.
      METHODS: One hundred and four consecutive pts with a first transmural MI without
      clinical contraindication (heart failure, moderate or severe mitral
      regurgitation, severe postinfarction angina, claudication or severe orthopedic
      problems) were randomly assigned to a rehabilitation group (A) and to a control
      group (B). Ten days after acute MI all pts underwent a coronary angiography. A
      complete echocardiographic examination was performed 10 and 90 days after MI, and
      an ergometric evaluation 20 and 90 days after MI. Ventricle volumes, ejection
      fraction (EF) and wall motion score were calculated by a two-dimensional
      echocardiogram. Thirteen pts (12.5%) were excluded from the study because of the
      bad quality of the echocardiographic images. There were 8 dropouts (7.8%) due to
      bypass surgery or to coronary angioplasty. Of the 83 pts who have concluded the
      study 46 (55%) belonged to the Group A and 37 (45%) to the Group B. Thirty-six
      had anterior MI (20 Group A), 41 inferior MI (22 Group A) and 6 lateral or
      posterolateral MI (4 Group A). RESULTS: At the base-line the ventricular volumes,
      the EF, the wall motion score and the Total Work Capacity (TWC) were not
      different in the two groups. Three months after the MI the pts of the Group A
      demonstrated, in comparison with the controls, a reduction of left ventricle end
      diastolic volume index (EDVi 75.4 +/- 18.1 ml/m2 vs 85.3 +/- 27.9 ml/m2; p <
      0.05) and an increased TWC (7146 +/- 3566 Kgm vs 4494 +/- 2728 Kgm; p < 0.001).
      In the Group A the comparison of the base-line data with those observed 3 months
      later showed a reduction of the EDVi from 81.9 +/- 16 to 75.4 +/- 18.1 p < 0.05,
      of the end-systolic volume index (ESVi) from 43.6 +/- 11.9 to 38.1 +/- 14 ml/m2,
      p < 0.05, of the wall motion score from 6.7 +/- 2.3 to 5.5 +/- 2.9 p < 0.05 and a
      great increase of the TWC (from 4483 +/- 2407 Kgm to 7146 +/- 3566 Kgm; p <
      0.0001). No parameter in the Group B showed any significant modification in the
      same period. The tendency to reduce the volume and improve the physical
      performance with exercise training was greater in the inferior MI (ESVi from 41.3
      +/- 12.3 to 34.7 +/- 11.6 ml/m2, p = 0.07 - TWC from 4652 +/- 2446 to 8115 +/-
      3954 Kgm, p < 0.001) than in the anterior MI (ESVi from 445.8 +/- 10.7 to 42.1 +/
      17.2 ml/m2, p = ns - TWC from 4085 +/- 2103 to 5829 +/- 2256 Kgm, p < 0.05).
      When comparing pts with an occluded infarct-related coronary artery with TIMI
      grade 0-2 flow with those with a patent one (TIMI grade 3 flow), no significant
      differences in any considered parameter except for the collateral vessels score
      were found (1.48 +/- 0.97 vs 0.29 +/- 1.64 p < 0.05). After 3 months 20 pts
      presented larger EDVi compared to the baseline, and compared to the 34 pts with a
      smaller EDVi, they had a higher serum myocardial enzymatic peak (LDH 2035 +/-
      1423 vs 1346 +/- 683 p < 0.01, CK 3096 +/- 2339 vs 2099 +/- 1520, p < 0.05) an
      inferior collateral score (0.47 +/- 0.77 vs 0.67 +/- 1.98, p < 0.01) and they
      mainly belonged to the Group B (55%). Twenty pts had an initial EF < or = 40%
      (range 22-40%): 5 of the 6 pts of this group, who increased the EDVi after 3
      months belonged to the Group B while 9 of the 10 pts who reduced it belonged to
      the Group A. CONCLUSIONS: Intensive physical training during the 3 months
      following a first transmural MI significantly improves the physical performance,
      reduces the ventricle size and improves the wall motion score. Such improvement
      could not be found in the control group and is not related to the patency of the
      culprit coronary artery. The pts with an inferior MI tended to gain a major
      advantage from the physical activity than the pts with an anterior

PMID- 7642050
TI  - [A measure of productivity in cardiology based on medical acts].
AB  - BACKGROUND: The decreased availability of economic resources, opposed to the
      increased demand for medical assistance, requires the use of methods to assess
      hospital efficiency. Purpose of our study was to evaluate and quantify the
      "products" of a cardiology department, as well as the changes in time of their
      production, by means of a catalogue of medical acts, set up for the French health
      system (CdAM). METHODS: The study includes the 224 admissions occurring in
      October 1987 and the 209 admissions of October 1992. Medical acts were recorded
      for all admissions, by number of acts as well as by weight of acts; this weight
      (expressed as complexity/cost index or ICR) takes into account the use of
      resources in terms of medical staff and nursing staff, together with technical
      resources, for each act. In 1987 and 1992, 1736 and 1603 acts were performed
      respectively, corresponding to a total weight of 24308 and 32194 ICR. RESULTS:
      The increased ICR appears to be related to an increase of invasive procedures,
      particularly of interventional electrophysiology and haemodynamics. By
      considering case mix, we observed an increment of ICR for the diagnosis of angina
      (from 194.3 to 227.4 ICR per patient), of arrhythmias (from 178.0 to 273.1) and
      of cardiomyopathy (from 95.6 to 179.7). CONCLUSIONS: In conclusion, CdAM allows
      to evaluate the cardiologic activity also in the Italian situation; the ICR of
      each act permits to estimate the human and technical burden, with subsequent easy
      internal and external comparisons.

PMID- 7642051
TI  - [The use of activated clotting time (ACT) to optimize heparinization during
      coronary angioplasty. The nursing personnel of the Hemodynamics Laboratory].
AB  - BACKGROUND: Suboptimal anticoagulation during coronary angioplasty is reported to
      be a major risk factor for occlusive complications. AIM: To define an appropriate
      timing for activated clotting time (ACT) tests in order to optimize
      anticoagulation with heparin during coronary angioplasty. METHODS: In 50
      consecutive procedures of elective angioplasty ACT was measured at baseline, at
      30, 60 and 120 min after heparin 10,000 U iv. In a subgroup of 25 patients (SG1)
      no additional heparin was given until the ACT test at 60 min. In a second
      subgroup of 25 patients (SG2) heparin 5,000 U was administered 30-45 min after
      the initial bolus if the ACT at 30 min was < 300 sec. ACT values were analyzed,
      and the correlation with the biological variables of patients was tested.
      RESULTS: In 20 patients out of 50 (40%) ACT values at 30 min were < 275 min.
      Heparin response was correlated with the body surface area but nor with age,
      neither with baseline ACT. Values at 60 min showed an adequate anticoagulation in
      only 6 patients (24%) in SG1 vs 21 (84%) in SG2. There were not complications.
      CONCLUSIONS: ACT testing 30 min after heparin 10,000 U during coronary
      angioplasty identifies most patients requiring early supplemental heparin. This
      yields an adequate anticoagulation at 60 min in most patients.

PMID- 7642052
TI  - [The rehabilitation of the cardiac patient in childhood. Its current status and
      outlook].
AB  - A cognitive survey of the state of the art of cardiac rehabilitation in the
      pediatric age in Italy has been carried out, involving in the inquiry 22 Centers
      of Pediatric Cardiology and Cardiac Surgery, and the Italian Societies of
      Cardiovascular Surgery and Functional Evaluation and Cardiac Rehabilitation, to
      assess whether this topic has the dimensions of a social problem. The results of
      this investigation show that there is in Italy an increasing population of post
      surgical patients, at least 3,000 per year which, together with about 500
      congenital and acquired non-operated patients with heart disease, could benefit
      by rehabilitation, early or late according to the age. Although considered
      "important" by most of the inquired cardiologists and cardiac surgeons there are
      in Italy, up to date, only two Centers suited for pediatric cardiac
      rehabilitation, which, further, treat only a limited number of patients.
      Guidelines for functional evaluation and rehabilitative programs are needed to be
      applied, possibly, in selected rehabilitative Centers for adults.

PMID- 7642053
TI  - [Successive ischemic events to a first acute myocardial infarct treated with
      fibrinolysis. An analysis of GISSI-2 patients considered reperfused by a clinical
      criterion. Participants in the GISSI-2 study. Gruppo Italiano per lo Studio della
      Streptochinasi nell'Infarto Miocardico].
AB  - BACKGROUND: The fast normalisation of the ST, after thrombolysis, is early sign
      related to coronary artery reperfusion and to prognosis of acute myocardial
      infarction (AMI). The aim of this analysis is the evaluation, in the large
      patients cohort of the GISSI-2 trial, of the relationship between the ST segment
      evolution after fibrinolytic therapy of AMI and recurrent ischaemic events
      [angina-reinfarction-ischaemia to exercise testing (ET)] at 30 and 180 days from
      randomisation. METHODS: Patients with first confirmed IMA and ECG before
      randomisation and 4 hours later, are chosen from GISSI-2 trial. A decrease > or =
      50% of the sigma ST elevation is adopted as cutoff for predicting coronary artery
      patency. Recanalisation is deemed to have occurred in group A patients versus not
      reperfused group B patients. The studied events are: angina, reinfarction,
      mortality, at 30 and 180 days from randomisation; ischemia to ET SL of 4-6 week.
      The results are presented in terms of Mantel-Haenszel odds ratios (OR) and 95%
      confidence intervals. RESULTS: Group A patients n. 5307 experienced versus group
      B patients n. 2718 a higher incidence of--in-hospital angina: 10.3% vs 7.9% OR
      1.30 (1.11-1.52)-180 days reinfarction: 2.9% Vs 1.7% OR 1.66 (1.19-2.30)
      Ischaemia to ET 25.4% vs 21.4% OR 1.24 (1.08-1.43), and a lower in-hospital
      mortality: 3.8% vs 8.5% OR 0.39 (0.32-0.48). CONCLUSIONS: Patients having
      indirect signs of early reperfusion post thrombolysis for IMA experience a higher
      in-hospital and 180 days recurrent ischaemia and a lower mortality; this fact can
      allow early identification of the patients who can receive a benefit from
      different therapeutical strategies.

PMID- 7642054
TI  - [The stratification of coronary risk in patients who are candidates for a
      vascular surgical intervention].

PMID- 7642055
TI  - [The esophagus as the cause of chest pain in patients with and without coronary
      disease].

PMID- 7642056
TI  - [The tomorrow of the operated congenital heart disease patient].

PMID- 7642057
TI  - [Is spontaneous echo contrast in the left atrium a risk factor for an embolic
      event?].

PMID- 7642058
TI  - [Biostatistics and clinical epidemiology. 4. The analysis of quantitative data: a
      comparison between groups].

PMID- 7642059
TI  - [Transesophageal echocardiography in patients with atrial fibrillation,
      candidates for cardioversion: usefulness and limitations].
AB  - BACKGROUND: Thromboembolic complications after electrical cardioversion (CV) of
      atrial fibrillation (AF) have been attributed to the dislodgment of preexistent
      left atrial thrombus during the resumption of atrial contraction. Transesophageal
      echocardiography (TEE) has been used to identify patients without thrombus, who
      potentially could undergo CV without anticoagulation. However, embolic events
      after CV in patients without evidence of thrombus on TEE have recently been
      reported. AIM OF THE STUDY: To evaluate if absence of thrombi or prethrombotic
      conditions such as spontaneous echo contrast or left atrial appendage disfunction
      can justify electrical CV without anticoagulant therapy. METHODS: Seventy-four
      patients with AF and candidates for CV underwent monoplane TEE. Patients were
      cardioverted without anticoagulation in case of: 1) absence of thrombus and/or
      spontaneous echocardiographic contrast and 2) good visualization of left atrial
      appendage, with a well defined peak blood flow velocity greater than 20 cm/sec.
      In all other cases, patients underwent anticoagulant therapy which started 3
      weeks before CV and continued for 4 weeks afterwards. RESULTS: Forty-six
      patients, without thrombus or "prethrombotic" conditions, did not receive
      anticoagulation, while 28 followed traditional therapy with warfarin. Four
      patients with a thrombus in the left atrial appendage were identified: 1 died of
      cerebral embolism 3 days after the beginning of anticoagulation, in another one
      CV was definitely deferred because of the persistence of thrombus after 1 month
      of warfarin therapy. One patient, with left atrial appendage disfunction, died
      suddenly after 5 days of anticoagulation. Two patients reverted spontaneously in
      sinus rhythm. Two patients refused electrical CV. The remaining 67 patients
      underwent electrical CV which was successful in 56 of them. Cerebral embolism
      occurred 24 hours after CV in one patient who did not receive anticoagulation.
      Repeat TEE soon after embolism showed absence of thrombus or spontaneous echo
      contrast, but the presence of low flow velocity in the left atrial appendage.
      CONCLUSIONS: In patients in AF candidates for CV, exclusion of thrombi or
      prethrombotic conditions by TEE does not exclude the risk of thromboembolic
      events and the need for anticoagulant therapy. Left atrial appendage function can
      be stunned or impaired immediately after CV, favouring a thrombogenic milieu and
      subsequent embolic events. Therapeutic anticoagulation at the time of as well as
      after cardioversion is actually recommended.

PMID- 7642060
TI  - [Usefulness of a protocol for carotid sinus massage in supine and erect postures
      in patients with syncope without other cardiovascular or neurological diseases].
AB  - BACKGROUND: Carotid sinus massage is a first level test when investigating the
      cause of syncope. It is normally performed in the supine and erect positions.
      However, there is no standard complete protocol. So we have devised a new
      protocol to evaluate the utility of carotid sinus massage in different postures
      and the influence of patients age on the response. METHODS: Two groups of
      subjects were selected: a group of 167 patients (mean age 50 ys +/- 18, 105
      males, 62 females) with a history of syncope without cardiovascular and
      neurological disease and 20 asymptomatic control subjects (mean age 52 ys +/- 13,
      11 males, 9 females). Carotid sinus massage was performed supine, just after
      passive tilt, after 5 minutes of tilt and just after passive return to supine. If
      a pause > 3" was detected, the protocol was repeated after atropine i.v.
      injection. DEFINITIONS: Borderline vasodepressor: blood pressure reduction > 30
      but < 50 mm Hg without symptoms; vasodepressor: blood pressure reduction > 50 mm
      Hg or > 30 mm Hg with symptoms like dizziness, vertigo or syncope;
      cardioinhibitory: pause > 3"; mixed: cardioinhibitory with blood pressure
      reduction > 30 mm Hg after atropine. RESULTS: Carotid sinus massage gave all
      informations in the supine position in 14 (12%) patients, after passive tilt in
      67 (57%), after 5 minutes of tilt in 30 (26%), and after return to supine in 6
      (5%). The responses were: 13 (8%) borderline vasodepressor, 32 (19%)
      vasodepressor, 2 (1%) cardioinhibitory, 70 (42%) mixed, 50 (30%) negative.
      Positive responses were more frequent in patients over 45 years (90% versus 43%).
      In the control group only 3 (15%) positive responses were elicited (2 borderline
      vasodepressor, and 1 vasodepressor, all in subjects over 45). CONCLUSIONS: This
      protocol for carotid sinus massage evidenced positive responses in 70% of
      patients with syncope without cardiovascular and neurological disease;
      cardioinhibitory responses are rare (2%); positive responses are more frequent in
      patients over 45 years; the protocol specificity was 85%.

PMID- 7642061
TI  - [Results of coronary surgery in mildly symptomatic patients with left ventricular
      dysfunction, multivessel disease and stenotic single residual patent vessel].
AB  - BACKGROUND: While efficacy of coronary artery bypass surgery in patients with
      depressed left ventricular function and myocardial ischemia is widely recognized,
      its results in patients in the absence of clinical evidence of myocardial
      ischemia remain uncertain. The purpose of this study was to evaluate the effects
      of coronary revascularization in comparison with conventional medical therapy in
      subjects with ischemic cardiomyopathy and myocardial ischemia presumed on the
      basis of angiographic anatomy but not demonstrated by functional testings.
      METHODS: We selected retrospectively patients who underwent coronary angiography
      from 1986 trough 1993 and met the following criteria: presence of three-vessel
      coronary artery disease, occlusion of two and significant luminal narrowing (> or
      = 50%) of the third major epicardial artery, left ventricular dysfunction
      (ejection fraction < or = 40%), no angina or presence of mild angina, absence of
      inducible ischemia on exercise test and, when performed, of redistribution in the
      vascular territory of the patent vessel. RESULTS: Thirty-one consecutive patients
      underwent isolated surgical revascularization treatment, while thirty medically
      treated patients with matched clinical characteristics were selected. Age (61 +/-
      10 vs 62 +/- 9), gender (M/F 27/3 vs 24/7), NYHA class I-II (53 vs 62%) or NYHA
      III-IV (47 vs 38%), incidence of previous infarction (87 vs 94%), number of
      reversible defects in the vascular territory of the patient vessel on stress
      scintigraphy (0.6 vs 0.5), patent vessel (right coronary artery 7 vs 10; left
      circumflex 14 vs 12; left anterior descending 9 vs 9) and left ventricular
      ejection fraction (28 +/- 8 vs 31 +/- 7), were similar in the two groups (medical
      vs surgical). Surgically treated patients exhibited a lower proportion of overall
      cardiac deaths (7/31, 23% vs 19/30, 63%; p < 0.001), and more prolonged survival
      (67 +/- 9.3 vs 34 +/- 2.5 months; p = 0.04, Mantel and Cox test) than medically
      treated patients, respectively. The incidence of perioperative myocardial
      infarction was 10% (3/31). Causes of cardiac death were myocardial ischemia
      (9/19; 47%), sudden death (5/19; 26%) and heart failure (5/19; 26%) in medical
      patients, while were surgery (3 cases) and surgery related infection (1 case)
      (total 4/7; 57%), myocardial ischemia (1/7; 14%), sudden death (1/7; 14%) and
      heart failure (1/7; 14%) in surgical patients. Cox proportional hazard regression
      analysis with survival as the dependent variable, identified treatment, surgical
      or medical, as the best predictor of cardiac events (chi square improvement 9.36,
      p = 0.002). The next most powerful predictors were NYHA class and ACE-inhibitors
      treatment (chi square improvement 4.47 and 2.79, respectively). CONCLUSIONS: In
      patients with left ventricular dysfunction, multivessel coronary artery disease
      and single patent but stenotic residual vessel, coronary artery bypass grafting
      appear to offer a better survival than medical therapy, even in the absence of
      clinically evident myocardial ischemia.

PMID- 7642062
TI  - [An epidemiological survey of cardiovascular disease risk factors in 18-year-old
      males during their medical check-up at an Army recruiting center in the province
      of Verona].
AB  - Between January and December 1992 an epidemiological survey on the risk factors
      for cardiovascular disease in eighteen-year old boys during call-up has been
      performed in Verona. The study involved 3426 subjects: 100% of the boys coming
      from the metropolitan area and 65% of those coming from the non-metropolitan
      areas. A family history of hypertension was found in 9.54% of the subjects and a
      family history of myocardial infarction or sudden death was found in 4.54% of the
      subjects. 0.18% of the population reported diabetes and 2% hypertension.
      Prevalence of smoke addiction was 39.1% and in this group 17.54% smoked > or = 20
      cigarettes/day. Prevalence of smoke addiction was significantly greater in the
      boys having one or both smoking parents (p < 0.001), in working people in respect
      to students (p < 0.001), in boys from metropolitan in respect to those from non
      metropolitan areas (p = 0.033), and among those not practising sport activity (p
      < 0.001). Mean systolic and diastolic blood pressure were 130.16 +/- 13/74.48 +/-
      9 mm Hg and 90th percentile was 149/87 mm Hg. Systolic and diastolic blood
      pressure were significantly lower in boys from metropolitan in respect to those
      from non-metropolitan areas and in smokers in respect to non smokers. A body mass
      index > or = 30 was found in 3.04% of the subjects, the body mass index being
      directly related to systolic and diastolic blood pressure (p < 0.001). Total
      cholesterol performed on a voluntary basis from capillary blood samples by
      Reflotron System was determined in 80.06% of the subjects. Mean blood cholesterol
      was 139.1 +/- 28 mg/dL and 90th percentile's value was 182 mg/dL. Mean blood
      cholesterol was significantly lower in non-metropolitan in respect to
      metropolitan areas (p = 0.033). 44.48% of the subjects had one or more risk
      factors, 5.22% had two risk factors and 0.67% three or more risk factors for
      cardiovascular disease. This study shows that 1) in this population of young
      people a significant part is exposed to one or more cardiovascular risk factors;
      2) social and environmental factors affect, sometimes deeply, the prevalence of
      cardiovascular risk factors; 3) The visit for call-up appears to be important in
      the setting-up of a strategy of primary prevention for cardiovascular disease.

PMID- 7642063
TI  - [Coronary angioplasty during acute myocardial infarction].
AB  - BACKGROUND: Percutaneous coronary angioplasty (PTCA) is an effective method to
      achieve myocardial reperfusion in acute myocardial infarction. In order to
      identify the predictors of primary success and major complications, we reviewed
      our experience in 107 patients (pts) who underwent PTCA of a totally occluded
      infarct-related coronary artery (IRA) within 24 hours (h) after the onset of
      symptoms. METHODS AND RESULTS: PTCA was successful in 92 pts (86%); PTCA failed
      without complications in 9 pts (8.4%), major complication (death and urgent
      coronary artery surgery) occurred in 6 pts (5.6%). Rescue PTCA was performed in
      31% of cases and had similar success rate when compared to direct PTCA (85 vs
      86%, p = NS). Pts with successful PTCA had repeat angiography 24 h after the
      procedure. According to primary and 24 h results, pts were divided into 3 groups:
      primary success with 24 h stable result (Group A: 76 pts, 71%); primary success
      with 24 h deterioration (Group B: 16 pts, 15%), among which 4 pts showed total
      reocclusion; primary failure (Group C: 15 pts, 14%). A longer time delay from
      symptoms onset (p < 0.05), cardiogenic shock (p < 0.001), previous bypass surgery
      (p < 0.05) were correlated with worse short-term outcome by univariate analysis.
      When compared to Group A, pts in Group C showed a lower EF (42 +/- 14 vs 51 +/-
      16%, p < 0.05). IRA diameter was greater in Group A (3.1 +/- 0.4 mm) when
      compared to Group B (2.7 +/- 0.4 mm, p < 0.05) and Group C (2.7 +/- 0.5 mm, p <
      0.05). Absence of cardiogenic shock (p < 0.001), decreasing time from symptoms
      onset (p < 0.01) and increasing ejection fraction (EF) (p < 0.05) were
      independent predictors of primary success by multivariate analysis. Cardiogenic
      shock (p < 0.001) and decreasing EF (p < 0.05) were independent predictors of
      major complications. CONCLUSIONS: PTCA of IRA is effective within 24 h from
      symptoms onset. Procedural failure is infrequent, usually occurring in patients
      with high-risk baseline characteristics.

PMID- 7642064
TI  - [Aneurysm of the common trunk of the left coronary artery. Case report and review
      of the literature].
AB  - Up to date only 13 cases of left main coronary artery aneurysms have been
      reported in literature; of these, 8 were associated with atherosclerosis. This
      report details the case of a large aneurysm of left main coronary artery
      angiographically documented in 46-year old man with exertional angina pectoris
      and myocardial infarction.

PMID- 7642065
TI  - [Direct PTCA in acute myocardial infarct].

PMID- 7642066
TI  - Radionuclide angiography: clinical applications. Gruppo Italiano di Cardiologia
      Nucleare (ANMCO-AIMN).

PMID- 7642067
TI  - The role of scintigraphic perfusion imaging in the evaluation of patients before
      and after myocardial revascularization. Gruppo Italiano di Cardiologia Nucleare
      (ANMCO-AIMN).

PMID- 7642068
TI  - [Doppler tissue imaging: current status and future prospects].
AB  - Colour Doppler myocardial imaging is a new technique which allows the
      visualization in the colour Doppler of myocardial tissues, instead of blood pool
      imaging. To permit the acquisition of this information some modifications are
      essential in the machine. The gain has to be reduced so that, firstly, the echoes
      from ventricular walls were similar to those from the blood pool. Secondly the
      Doppler velocity range has to be reduced to correspond to the normal velocity of
      the ventricular wall. These modifications allow the tissue echoes to pass the
      clutter filter and to be displayed in colour on the video screen. This technique
      may be able to evaluate the velocity of myocardial tissue, the acceleration and
      the strength within the myocardial wall with these maps, obtained by
      modifications in the software, called Velocity Map, Acceleration Map, Energy Map.
      The clinical applications of this technique are: 1) in the area of myocardial
      functions e.g.: measurements, volumes, diastolic functions; 2) in the area of
      myocardial ischemia e.g.: wall motion abnormalities, viability studies, perfusion
      with contrast agents, stress echo, infarct identification; 3) in the area of
      myocardial depolarisation e.g.: arrhythmias evaluation, ablation monitoring.
      Doppler tissue imaging in spite of good results obtained, needs a large clinical
      studies.

PMID- 7642069
TI  - [Current phase of transformation of our health system].

PMID- 7642070
TI  - [Echocardiography in the evaluation of arrhythmogenic right ventricular
      dysplasia].

PMID- 7642071
TI  - [Biostatistics and clinical epidemiology. 5. Analysis of quantitative data:
      relations between groups].

PMID- 7642072
TI  - [Rubric of good and less good drugs. Clonidine].

PMID- 7642073
TI  - [Experimental study of the effectiveness of interleukin-1beta in radiation
      injury].
AB  - The experiments on mice exposed to radiation (6.5 Gy, LD 80/30) discovered that
      human recombinant interleukin-1 beta after administration on postradiation hour 1
      3 increased the animals' survival by 40-70%. Interleukin-1 beta reduced
      leukopenia and enhanced the recovery of bone marrow cell elements. The use of the
      preparation as an early pathogenetic treatment of irradiation damage holds
      promise.

PMID- 7642074
TI  - [Features of hemocoagulation potential, antithrombogenic properties of the
      vascular wall and platelet functional activity in workers of an expeditionary
      team].
AB  - Hemostasis was studied in 373 oilmen aged 20-40 working according to expedition
      schedules. Control subjects were not engaged in expeditions. Expedition labor was
      found to cause hypercoagulemia with parallel decline in anticoagulant activity.
      Vascular wall ability to release anticoagulants and fibrinolysis activators in
      the blood stream appeared inhibited. Platelet count in the peripheral blood,
      platelet aggregation, platelet factor III activity were increased. The duration
      of expedition service and phases of working cycle seem to affect hemostatic
      parameters.

PMID- 7642075
TI  - [Hematologic characteristics of patients with chronic alcoholism and people at
      risk].
AB  - Red cell functional and structural characteristics were studied in 146 patients
      with chronic alcoholism (CA) stage II, 47 workers of hydrolysis plant exposed to
      ethyl alcohol inhalations (risk group) and 100 healthy controls (male blood
      donors). It was found that CA patients and risk group subjects have similar
      changes in the erythron system, though in alcoholics these were much more
      pronounced: elevated count of red cells, blood hemoglobin concentration,
      hematocrit, increased mean size of red cells and intensity of 24-h erythropoiesis
      in reduced red cell survival. Scanning electron microscopy revealed abnormal
      surface architectonics of red cells. Insulin-deposition and insulin-transport
      functions of the latter were also impaired. The evidence obtained may prove
      useful for specification of of risk groups and somatic diseases at various
      alcoholism stages.

PMID- 7642076
TI  - [Hypoxia of tissue peripheral shunting in massive transfusion of erythrocytes and
      whole donor blood].
AB  - In response to correction of lethal and sublethal blood loss with excessive
      quantities of donor blood two types of cardiovascular adverse reactions may occur
      immediately after transfusion: either increased or decreased minute blood volume.
      This conclusion was made after 65 dog experiments on hemodynamics and blood
      gases. Though the absolute value of cardiac output changes differently in both
      cases there are signs of oxygen insufficiency.

PMID- 7642077
TI  - [Emergency laparoscopy in hematology practice].
AB  - Outcomes of urgent laparoscopy performed in 31 patients with various
      hematological diseases were favourable in spite of serious condition of the
      patients and apparent hemorrhagic syndrome. No laparoscopy-related complications
      were registered. Due to endoscopic investigation surgical intervention was
      rejected as unjustified in half of the examinees, 11 operations were performed
      just in time. Diagnostic difficulties in acute abdominal conditions requiring
      surgery and indications to laparoscopy in suspected perforations, peritonitis,
      acute appendicitis, hemorrhages are detailed.

PMID- 7642078
TI  - [Cryopreservation of erythrocytes at moderately low temperature with
      transportation simulation].
AB  - Cryopreservation of red cell mass at -75-80 degrees C as concentrates warrants
      its prolonged storage (up to 1.5 years) in functional condition and transfusion
      without centrifugation. The above cryoconcentrates are resistant to temperature
      fluctuations and keep morphologically and functionally safe in response to a
      temperature rise to -32 degrees C (transportation simulation). Transport freezers
      efficient for frozen erythrocytes transportation have been tested.

PMID- 7642079
TI  - [Prolonged storage at +4 degrees C of cryopreserved and thawed erythrocytes].
AB  - A new method of taking out of storage is offered for red cells cryopreserved in
      the presence of low-concentration glycerin (15-20%) in relatively low temperature
      (-38 +/- 2 degrees C) and in liquid nitrogen. The new approach implies washing of
      erythrocytes not immediately after thawing but just before the transfusion. The
      delay in thawed erythrocytes washing warrants their safety and functional
      capacity throughout 3-week storage at + 4 degrees C after cryopreservation at -38
      +/- 2 degrees C and within 2 weeks after freezing in liquid nitrogen.

PMID- 7642080
TI  - [Changes in the T-cell component in patients with subleukemic myelosis at various
      stages of the pathologic process].
AB  - T-cell immunity was assessed in 111 patients with subleukemic myelosis. In such
      patients with large tumor mass and leukemia exacerbation the amount of
      immunocompetent cells and their functional activity were reduced more
      prominently. Association of infection and inflammation promoted aggravation of
      initial immune deficiency.

PMID- 7642081
TI  - [Biological properties of microflora in pyo-inflammatory complications in
      hematologic patients].
AB  - The occurrence of opportunistic bacteria isolated from hematological inpatients
      with pyo-inflammatory complications and strain affiliation of these bacteria were
      investigated. Gram-negative and gram-positive agents made up 51.9 and 48.1%,
      respectively, of the 1699 bacterial strains obtained from 814 patients.
      Klebsiella, E.coli, Pseudomonas aeruginosa, Proteus strains were able to produce
      LT-enterotoxin showing weak enterohemolytic activity, were sensitive to
      gentamicin and claforan and insensitive to carbenicillin, ampicillin, oxacilin,
      tetracycline, erythromycin.

PMID- 7642082
TI  - [Epidemiologic evaluation of immune deficiency and other chronic pathology among
      the adult population of Bryansk region, living in radionuclide-contaminated
      territory].
AB  - Immune deficiency epidemiological survey covered adult population of the town of
      Vyshkov in the Bryansk region of Russia referred to the zone of radionuclide
      contamination hazard after the Chernobyl accident. A total of 3892 subjects were
      examined for the leading immunopathological syndromes (infectious, allergic
      atopic, autoimmune, lymphoproliferative) according to a specially devised
      technique developed in the Research Institute of Immunology in Moscow. Immune
      deficiency risk group made up 10.25% which is much higher than relevant value for
      control rural population of the southern Urals exposed to low-dose radiation and
      of polluted region in the East Siberia. The quantitative analysis indicated more
      frequent occurrence of infectious and lymphoproliferative syndromes of immune
      deficiency in the absence of radiation-related allergic diseases in the town of
      Vyshkov.

PMID- 7642083
TI  - [Morphologic characteristics of lymphocytes 6 years after the Chernobyl
      accident].
AB  - The examination of peripheral blood lymphocytes from persons exposed to low-dose
      radiation after the Chernobyl accident demonstrated that the exposure to
      radiation at the time of the accident and further living in the contaminated
      territory entail a significant increase in the number of cells with a large thick
      nucleus and scare cytoplasm. Such morphological picture may be attributed to
      stable adaptation typical for persistent activation of the general adaptation
      syndrome and is explained by adaptation-stress relations.

PMID- 7642084
TI  - [Parenteral nutrition in patients with chronic renal insufficiency before and
      after kidney transplantation].

PMID- 7642085
TI  - [The degree of severity of immune disorders and factors influencing the results
      of their correction in patients with chronic myeloproliferative diseases].
AB  - Immune status in relation to tumor progression was evaluated in 175 patients with
      chronic myeloproliferative diseases. 113 of them had chronic myeloid leukemia, 62
      chronic subleukemic myelosis. It was established that immunologic reactivity
      decline correlated with the rate of tumor progression. The degree of immune
      deficiency should be taken into consideration in selection of patients for
      immunotherapy.

PMID- 7642086
TI  - [Changes in the activity of endonucleolysis of nuclear DNA in children with acute
      leukemia].
AB  - The previously established fact of low activity of Ca, Mg-dependent
      endonucleolysis of cell nucleus DNA in lymphoproliferative diseases (CME
      activity) brought the authors to study intranuclear characteristics of lymphoid
      cells in childhood acute lymphoblastic leukemia (ALL). The intensity of DNA
      endonucleolysis was measured in 0.7% agarose gel using electrophoresis.
      Peripheral blood and bone marrow samples from 13 untreated ALL patients and 23
      children in remission were examined. The age of the patients ranged from 4 to 14
      years. CME-activity before treatment appeared to be 2-10 times less than normal
      in 8 out of 13 patients. In bone marrow cell nuclei CME-activity was universally
      reduced 3-20-fold. In ALL remission endonuclease activity in blood and bone
      marrow cells returned to normal.

PMID- 7642087
TI  - Human DNA helicase IV is nucleolin, an RNA helicase modulated by phosphorylation.
AB  - The cDNA encoding human DNA helicase IV (HDH IV), a 100-kDa protein which unwinds
      DNA in the 5' to 3' direction with respect to the bound strand, was cloned and
      sequenced. It was found to be identical to the human cDNA encoding nucleolin, a
      ubiquitous eukaryotic protein essential for pre-ribosome assembly. HDH
      IV/nucleolin can unwind RNA-RNA duplexes, as well as DNA-DNA and DNA-RNA
      duplexes. Phosphorylation of HDH IV/nucleolin by cdc2 kinase and casein kinase II
      enhanced its unwinding activity in an additive way. The Gly-rich C-terminal
      domain possesses a limited ATP-dependent duplex-unwinding activity which
      contributes to the helicase activity of HDH IV/nucleolin.

PMID- 7642088
TI  - Unique features in the mitochondrial D-loop region of the European seabass
      Dicentrarchus labrax.
AB  - We have cloned and sequenced the displacement-loop (D-loop) region of the
      mitochondrial DNA (mtDNA) from the European seabass Dicentrarchus labrax (Dl).
      This sequencing revealed the presence of four tandemly repeated elements (R1, R2,
      R3 and R4); the individual variation in mtDNA total length is entirely accounted
      for by their variable number. The individuals examined also possessed an
      imperfect copy of one of the tandem repeats (psi R2). At least one termination
      associated sequence (TAS) is present in each of the repeats and in two copies 5'
      upstream from the tandem array as well. The alignment of the Dl D-loop region
      with D-loop sequences from four other Teleosts and one Chondrosteus showed the Dl
      sequence to be larger than that of other fish. The extraordinary length of the Dl
      D-loop sequence is also due to the 5' and 3' regions that are flanking the tandem
      array, the largest ones to date analyzed in fish. In this study, we also report
      the unique organization and localization of putative TAS and conserved-sequence
      block (CSB) elements, and the presence of a conserved 218-bp sequence in the Dl D
      loop region.

PMID- 7642089
TI  - Characterization of the osteoclast vacuolar H(+)-ATPase B-subunit.
AB  - During bone resorption, osteoclasts acidify the extracellular bone resorbing
      compartment via a vacuolar H(+)-ATPase (V-ATPase), which resides in the ruffled
      border membrane. In an effort to characterize the composition of the osteoclast V
      ATPase catalytic domain, we have isolated a cDNA clone that encodes the V-ATPase
      B-subunit from a cDNA library constructed from highly purified chicken
      osteoclasts. Comparison of the predicted amino-acid sequence with the published
      sequences of isoforms of V-ATPase B-subunits from other sources revealed that the
      chicken osteoclast B-subunit is brain type and not kidney type. Furthermore, only
      clones encoding the brain type isoform of subunit B could be generated by PCR
      from a cDNA library prepared from human osteoclastoma osteoclast-like cells.
      Northern blot analysis revealed that two B-subunit mRNAs, approx. 1.7 and 3.5 kb
      in length, are expressed in chicken bone marrow mono-nuclear cells, brain and
      kidney, although the relative amounts of these two transcripts were different in
      each tissue. In brain, the 3.5-kb mRNA was predominantly expressed. In bone
      marrow cells, the levels of the 1.7-kb mRNA were higher than in other tissues and
      expression of this message was increased by 1,25-dihydroxyvitamin D-3, suggesting
      that this mRNA is specifically upregulated during osteoclast
      differentiation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7642090
TI  - The position of integration affects expression of the A gamma-globin-encoding
      gene linked to HS3 in transgenic mice.
AB  - Proper expression of the human beta-globin (beta Glb) locus is dependent on the
      presence of a major regulatory element located upstream from the beta Glb gene
      cluster, the locus control region (LCR). The LCR, as well as the individual DNase
      I-hypersensitive sites from which it is composed, have been shown to provide
      position-of-integration-independent expression in transgenic mice. Here, we
      report that a transgenic founder carrying multiple integrations of a
      hypersensitive site 3::A gamma globin gene (HS3::A gamma) construct produced
      three types of progeny, one with zero A gamma expression in the adult stage, one
      with minimal A gamma expression (1% of A gamma-expressing cells) and one with
      abundant A gamma expression (100% A gamma-expressing cells). The possibility that
      these phenotypes were due to parental imprinting or to DNA rearrangements of the
      transgene or to point mutations of the HS3 core or the A gamma promoter were
      excluded. The pattern of inheritance of the three HS3::A gamma transgene
      phenotypes indicate that the transgene has integrated into three different
      chromosomes. These results provide direct evidence that the HS3 of the LCR is not
      sufficient to protect the A gamma gene from position effects excerted by the
      surrounding chromatin.

PMID- 7642091
TI  - Expression of the measles virus nucleoprotein gene in Escherichia coli and
      assembly of nucleocapsid-like structures.
AB  - To investigate the use of fusion systems to aid the purification of recombinant
      proteins for structure/function studies and potential uses as diagnostic
      reagents, the measles virus (MV) gene encoding the nucleoprotein was cloned and
      expressed in Escherichia coli in three forms: as a full-length intact protein and
      as two fusion proteins. Expression of the intact N gene under the control of the
      tac promoter in the pTrc99c plasmid produced a protein of the correct size (60
      kDa) which represented approx. 4% of the total cellular protein, and was
      recognised by known measles positive human sera. 'Herringbone' structures
      characteristic of paramyxovirus nucleocapsids (NuC) were identified in fractured
      cells examined by electron microscopy. The production of NuC-like structures in a
      prokaryotic cell indicates folding of the nucleoprotein can occur in the absence
      of MV genomic RNA, other MV-encoded gene products and eukaryotic cell proteins or
      RNA, to produce structures which are morphologically and antigenically similar to
      those seen in virus-infected cells. Conversely, synthesis of N protein as a
      fusion protein with either E. coli beta-galactosidase or the E. coli maltose
      binding protein resulted in the production of fused proteins which could not be
      assembled into NuC-like structures or readily used as diagnostic reagents.
      However, the ability of MV N protein to form NuC-like structures in E. coli will
      facilitate structure/function and mutational analysis of the NuC protein.

PMID- 7642092
TI  - Deletion or alteration of hydrophobic amino acids at the first and the third
      transmembrane domains of hepatitis B surface antigen enhances its production in
      Escherichia coli.
AB  - To investigate the failure of high-level production of hepatitis B viral (HBV)
      surface antigen (HBsAg), including three authentic forms, large (L), middle (M)
      and major/small (S) HBsAg, in Escherichia coli, we employed the high-expression
      vector pGEX containing the glutathione S-transferase-encoding gene (GST) to study
      HBsAg production. Different fragments of HBV DNA containing the entire pre-S1/pre
      S2/S region (for L protein), or partial pre-S1, pre-S2, pre-S1/pre-S2 and pre
      S2/S region (for M protein), were fused downstream from the GST gene, in order to
      obtain five plasmids which encode GST-HBsAg fusion proteins. SDS-PAGE analyses
      revealed that cells containing plasmids with a full-length S region (pGLS and
      pGMS) produced undetectable GST-HBsAg fusion proteins, in contrast to those cells
      harboring plasmids without the S region (pGS1, pGS2 and pGS1S2), which
      synthesized fusion proteins in 3-10% of the total cellular protein. Using an
      immunoblot method to screen HBsAg production in cells which harbored plasmids
      derived from exonuclease BAL 31-digested pGLS, we obtained eight positive clones.
      Nucleotide sequence analyses of plasmids from the positive clones revealed that
      termination, deletion or frameshift occurred at the regions encoding either the
      first or the third transmembrane domain of the major HBsAg. Correlation between
      the production level of GST-HBsAg fusion proteins and their constituent and
      arrangement of amino acids (aa) at the last 20 aa among 15 clones suggested that
      the fusion protein ended with a longer stretch of or a higher ratio of
      hydrophobic aa had a lower production in E. coli.

PMID- 7642093
TI  - A 3.5-kb DNA fragment contains the cis-regulatory elements for retina-specific
      expression and partial dosage compensation of the Arrestin B (ArrB) gene of
      Drosophila miranda.
AB  - A 3.5-kb genomic DNA fragment containing the X1R chromosome-linked retina
      specific Arrestin B gene (also called Arrestin 2) of Drosophila miranda (ArrB-mr)
      was introduced into the Drosophila melanogaster genome via germ-line
      transformation. The results showed that the ArrB-mr transgene was expressed only
      in the retina of the transformed flies. The transgene also showed male-specific
      transcriptional hyperactivation or dosage compensation, but the level was found
      to be 71-79% of the expected value. The endogenous autosomal ArrB-ml gene of D.
      melanogaster, as expected, was not found to be dosage compensated in the
      transformants. Thus, while the cis-regulatory elements for retina-specific
      expression are fully present in the 3.5-kb DNA, part of the sequences needed for
      full dosage compensation are missing in this DNA. Nucleotide (nt) sequence
      comparison of the upstream DNA revealed that both ArrB-mr and ArrB-ml possess a
      putative TATA box at -32 nt. They also have an 11-bp motif (5'-AATCCAGTTAG)
      similar to the photoreceptor conserved element I (PCE I) believed to play an
      important role in retina-specific expression of the D. melanogaster opsin and
      mouse Arr genes. In addition, both genes contain a TGACCT motif which is known to
      bind a transcription factor activated by retinoic acid and vitamin D3. However,
      five tandem repeats of a heptanucleotide sequence (TGGGCNR) and a 29-bp sequence
      with the potential to form a stem-loop structure, are found only in the ArrB-ml
      gene. These sequences may play an important role in dosage compensation of the
      X1R-linked ArrB-mr gene.

PMID- 7642094
TI  - A novel host-vector system for direct selection of recombinant baculoviruses
      (bacmids) in Escherichia coli.
AB  - Site-specific transposition in Escherichia coli was used to introduce foreign
      genes into the Autographica californica nuclear polyhedrosis baculovirus genome.
      Using a temperature-sensitive donor plasmid and an E. coli host strain with an
      occupied Tn7 attachment site it was possible to select directly for 'bacmid'
      recombinants at 44 degrees C. A blue to white color screen provided further
      confirmation of insertion at the correct site in the baculovirus genome. After
      cloning the gene of interest into a donor plasmid, a single transformation and
      plating on selective medium resulted in homogeneous baculovirus DNA which could
      immediately be transfected into insect cells. The utility of the host-vector
      system for expression in insect cells was illustrated using three heterologous
      genes encoding beta-glucuronidase, human N-myristoyl transferase and murine
      preproguanylin. Using this approach, bacmid recombinants could be produced at a
      frequency of > or = 10(5) per micrograms input DNA. This system should not only
      greatly enhance the ability to obtain recombinant viruses for heterologous
      protein production, but should also be useful for protein engineering
      applications and expression cloning in insect cells.

PMID- 7642095
TI  - RAD51 homologues in Xenopus laevis: two distinct genes are highly expressed in
      ovary and testis.
AB  - The RAD51 gene is a eukaryotic counterpart of the Escherichia coli recA gene
      which is involved in genetic recombination. Two distinct Xenopus laevis RAD51
      cDNA clones (XRAD51.1 and XRAD51.2) were isolated from an oocyte cDNA library
      using the human RAD51 cDNA (HsRAD51) as a probe. Sequence analysis revealed that
      98.2% of the amino-acid residues were identical between XRAD51.1 and XRAD51.2,
      and that both were 95% identical to HsRAD51. Both of the XRAD51 genes were
      expressed at a higher level in ovary and testis than in other somatic tissues,
      suggesting their involvement in meiotic recombination. The expression of XRAD51.1
      was about eightfold in excess of that of XRAD51.2 in all of the tissues examined.
      Analysis of the rates of synonymous substitution in the coding sequences of the
      two XRAD51 suggests that these two genes diverged about 50 million years ago. The
      structural similarities of the XRAD51 proteins to RecA in E. coli and Rad51 in
      yeasts or vertebrates are discussed.

PMID- 7642096
TI  - Structure and metal-regulated expression of the gene encoding Xenopus laevis
      metallothionein-A.
AB  - To investigate the regulation of amphibian metallothionein(MT)-encoding genes, we
      have isolated and sequenced the XlMT-A gene encoding Xenopus laevis (Xl) MT-A.
      The gene displays an overall structure similar to that of mammalian MT, with
      three exons interrupted by two introns. The promoter region contains a typical
      TATA box and two metal regulatory elements (MRE) within the first 100 bp upstream
      from the transcription start point (tsp). The transition metal ion (Mc2+)
      inducibility of the promoter was studied by transient expression experiments in
      CV-1 African green monkey kidney cells, using different DNA fragments from the 5'
      flanking region of XlMT-A fused to the bacterial cat reporter gene. The first 145
      bp upstream from the tsp are sufficient to confer inducibility of cat by Cd2+.
      Constructs bearing only the most proximal MRE are not inducible by Me2+, thus
      suggesting that both MRE are required for Me2+ induction. Recognition sites for
      the transcription factors, AP-1 and AP-2, are located within the first 180 bp of
      the promoter region and these elements appear to be involved in controlling the
      constitutive basal level of expression of this MT.

PMID- 7642097
TI  - The cDNA encoding Xenopus laevis heat-shock factor 1 (XHSF1): nucleotide and
      deduced amino-acid sequences, and properties of the encoded protein.
AB  - We have isolated a cDNA encoding Xenopus laevis (Xl) heat-shock factor 1 (XHSF1).
      XHSF1, translated from the mRNA synthesized in vitro, will bind specifically to
      the Xl hsp70 promoter (hsp70). Microinjection of XHSF1 mRNA into Xl oocytes leads
      to synthesis of XHSF1 which accumulates in the nucleus and selectively activates
      Xl phsp70p activity at 18 degrees C.

PMID- 7642098
TI  - Cloning of a Xenopus laevis cDNA encoding focal adhesion kinase (FAK) and
      expression during early development.
AB  - Focal adhesion kinase (FAK) is a widely produced nonreceptor protein-tyrosine
      kinase thought to participate in signalling pathways activated in response to
      cell interaction with the extracellular matrix. Fibronectin-dependent cell
      adhesion mediated by integrin receptors plays a critical role in mesodermal cell
      migration during amphibian gastrulation in early development. As a first step
      toward understanding the role of FAK in Xenopus laevis (Xl) early development, we
      isolated cDNAs encoding Xl FAK and deduced the entire amino acid (aa) sequence.
      Xl FAK has 89-91% overall identity to the homologs previously described from
      mouse, human and chicken sources. Within the catalytic domain, the aa identity is
      about 97%. Northern blot analysis revealed that abundant maternal FAK transcript
      is present in Xl eggs, with levels decreasing slightly through cleavage and early
      blastula stages. At early gastrulation, the FAK mRNA level becomes modestly
      elevated, followed by a steady decline through late gastrulation. The mRNA level
      undergoes a further drop at the neurula stage, then begins a steady increase
      through the tailbud and tadpole stages. These data indicate that the steady-state
      level of FAK mRNA is regulated during Xl early development, and are consistent
      with a proposed role for FAK in the process of gastrulation.

PMID- 7642099
TI  - cDNA and amino-acid sequences and organization of the gene encoding the B beta
      subunit of fibrinogen from Xenopus laevis.
AB  - Fibrinogen, the major blood-clotting protein, is made up of three chains, A
      alpha, B beta and gamma, which are synthesized and secreted by the liver. In this
      communication, we describe the complete cDNA sequence, deduced amino acid (aa)
      sequence and organization of the gene encoding the B beta subunit of fibrinogen
      from Xenopus laevis (Xl). The cDNA representing the predominant form of the B
      beta mRNA comprises 2390 nucleotides (nt), with an open reading frame of 1467 nt
      coding for a 488-aa protein. The percent identity between Xl B beta and that of
      other animals ranges from 50% for lamprey to 66% for human. The Xl B beta gene
      consists of nine exons, one more than found in the human gene. The exon/intron
      boundaries in the frog and human B beta genes are in exactly conserved positions,
      except for junctions in the highly variable fibrinopeptide-encoding regions.
      Three of the exon/intron boundaries in the Xl B beta gene are also analogous to
      ones in A alpha and gamma genes of other species, supporting the notion of a
      close evolutionary relationship between the genes for all three subunits. This
      analysis of B beta from an amphibian provides the first complete description of
      the arrangement of exons and introns in any fibrinogen subunit gene from a non
      mammal and gives insight into the most highly conserved aspects of fibrinogen
      protein structure and gene organization.

PMID- 7642100
TI  - A 67-kDa protein binding to the curved DNA in the main regulatory region of the
      rat mitochondrial genome.
AB  - We have purified, by sequence-specific affinity chromatography, a mitochondrial
      (mt) matrix protein which binds to the curved DNA located between the replication
      origin (ori) of the leading strand (ori-H) and the two transcription promoters in
      the rat mt genome. The protein was characterized by gel electrophoresis as a 67
      kDa polypeptide and seems to be involved in the DNA contact on the mt light
      strand. This protein differs (in the size and location of its DNA-binding site)
      from other DNA-binding proteins studied so far in animal mt systems. We suggest a
      role for the 67-kDa protein, assisted by other proteins, in regulating the
      initiation of leading-strand replication.

PMID- 7642101
TI  - The structure, organization and differential expression of the rat gene encoding
      biliverdin reductase.
AB  - Screening of phage lambda libraries and genomic polymerase chain reactions were
      employed to generate clones of the rat gene encoding biliverdin reductase (BVR),
      the penultimate enzyme in the heme metabolic pathway. This enzyme, which converts
      biliverdin to bilirubin, is unique among enzymes characterized to date in that it
      exhibits two pH optima, 6.75 and 8.7, and utilizes a different cofactor, NADH and
      NADPH, respectively, at each optimum. The gene, which is 12270 bp in length,
      consists of five exons and four introns; two introns are > or = 4 kb. Only two of
      the four splice sites conform to consensus donor/acceptor sequences. Primer
      extension indicates the presence of two distinct transcription start points (tsp)
      in kidney and brain, as well as an additional tsp present in kidney, but not in
      brain RNA. The gene lacks a conventional TATA-box; however, an overlapping pair
      of TATA-like sequences is found 80 nt upstream from the kidney-specific tsp. The
      promoter region contains binding sites for several known regulatory factors,
      including AP-1, HNF-5 and INF-1, as well as two partial (7/8) matches to the heat
      shock (HS) transcription factor-binding site. However, the time-course of the
      increase in message level, as determined by Northern blot analysis, indicates
      that BVR is not an early HS protein in that the relative abundance of mRNA is
      increased 6 h after hyperthermia and not at 1 h after HS. The approx. 1.6-kb BVR
      message is abundantly expressed in kidney, spleen, liver and brain, and at lower
      levels in the thymus, with minimal levels being detected in testis.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7642102
TI  - Sequences of the cDNAs encoding canine parathyroid hormone-related protein and
      parathyroid hormone.
AB  - The cDNA clones encoding canine parathyroid-hormone-related protein (cPTHrP) and
      parathyroid hormone (cPTH) have been isolated and sequenced. The predicted amino
      acid sequences of the mature canine homologs have a high degree of homology to
      human PTHrP (hPTHrP) and PTH (hPTH), especially in the biologically active
      regions. The cPTHrP cDNA is unique, since it has homology to exon 1A of hPTHrP
      which suggests that dogs utilize a promoter similar to P1 of hPTHrP which has not
      been demonstrated in other species.

PMID- 7642103
TI  - Cloning of the cDNA encoding neural adhesion molecule F3 from bovine brain.
AB  - We cloned a bovine cDNA encoding the neural adhesion molecule F3 and analyzed its
      nucleotide sequence. The coding region consisted of 3054 bp encoding 1018 amino
      acid (aa) residues. The M(r) calculated from the deduced aa sequence was 113,383.
      Bovine F3 had 93, 94 and 77% aa identity with the mouse, human and chicken
      homologs, respectively. Bovine F3, similar to those of chicken and human, was
      devoid of two aa residues (Ile-Thr) in the sixth immunoglobulin type C2-like
      domain, as compared with the mouse homolog. Parts of bovine F3 protein were
      overproduced in Escherichia coli. The antibodies raised against the recombinant
      proteins in rabbits reacted specifically with F3. F3 protein was detected in
      cerebellum, cerebrum and spinal cord in Western blot analysis.

PMID- 7642104
TI  - The cattle major histocompatibility complex (MHC) class-I possesses HLA-like
      promoters.
AB  - To study the genetic regulation of the cattle major histocompatibility complex
      (MHC) class-I, a cattle MHC class-I promoter DNA fragment was isolated and
      characterized for the first time. Semi-degenerate PCR was performed on cattle
      genomic DNA and the resulting product was isolated, subcloned and sequenced.
      Sequence comparison of the HLA-A, -B and -C promoters to the cloned product,
      designated BL3-6prmtr, revealed the cattle MHC class-I promoter to have close
      homology to human MHC class-I promoters. To address the ability of the cattle MHC
      class-I promoter to initiate transcription, BL3-6prmtr was subcloned into a
      luciferase reporter vector and transiently transfected into cattle and human B
      lymphoblastoid cell lines. A strong transcription initiation ability of BL3
      6prmtr was observed, including the ability of the enhancer A and interferon
      response sequence (IRS) to upregulate transcription initiation.

PMID- 7642106
TI  - Sequence of a human transcript expressed in T-lymphocytes and encoding a
      fibrinogen-like protein.
AB  - A murine cDNA sequence (termed pT49), encoding a protein related to the
      fibrinogen (Fib) beta and gamma chains, has been previously reported [Koyama et
      al., Proc. Natl. Acad. Sci. USA 84 (1987) 1609-1613]. We used a murine pT49 probe
      to screen a human small intestine cDNA library, and obtained a set of overlapping
      cDNA clones encoding a Fib-like protein that is 80% identical with the product of
      the murine pT49 gene. The deduced amino acid (aa) sequence contains a predicted
      signal peptide and five consensus motifs for N-linked glycosylation. The presence
      of conserved Cys residues involved in the assembly of the mature Fib complex and
      of two alpha-helical regions permissive for coiled-coil formation, suggests that
      this Fib-like protein may be secreted as a multichain complex. Two mRNA species
      of approx. 4.5 and approx. 1.5 kb were detected by Northern blot hybridization of
      a human pT49-homolog cDNA probe with RNA obtained from resting peripheral blood T
      lymphocytes. By RT-PCR analysis of purified peripheral blood T-lymphocyte
      subsets, we found expression of the pT49-homolog transcript in both CD3+/CD4+ and
      CD3+/CD8+ T-lymphocytes. The coding region of the human pT49-homolog cDNA was
      fused at its 3' end with a tag-coding sequence and was expressed in CHO cells.
      The corresponding gene product was immunoprecipitated with an anti-tag antibody
      from the cell lysate and from the culture supernatant of metabolically labeled
      transfectants and was identified as approx. 62 and approx. 64-70-kDa proteins,
      respectively.

PMID- 7642105
TI  - Cloning and analysis of the cDNA encoding the horse and donkey luteinizing
      hormone beta-subunits.
AB  - The coding regions of the horse (Equus caballus) and donkey (E. asinus)
      luteinizing hormone (LH) beta-subunit transcripts were cloned from pituitary
      gland RNA, in order to investigate their relationships to the corresponding
      equine chorionic gonadotropin (CG) beta-subunits and to further understand the
      unusual receptor-binding properties of equine LH and CG. The horse and donkey LH
      beta-subunit sequences were very similar (97% identity at the nucleotide (nt)
      level; 93% at the amino acid (aa) level), confirming their very close
      evolutionary linkage and also indicating that the C-terminal extension in both
      subunits occurred prior to the divergence of horse and donkeys. Furthermore,
      sequence comparisons and Southern blot analysis confirmed that in donkeys, as in
      horses, the pituitary (LH) and placental (CG) beta-subunits are almost certainly
      derived from a single gene. This contrasts with primates which have a single LH
      beta gene expressed in the pituitary and a family of separate CG beta genes that
      are expressed in the placenta. The deduced aa sequences also revealed several
      differences between the horse and donkey LH/CG beta-subunits that could explain
      their differences in biological activity. In addition, the study confirmed that
      the donkey subunit contains an additional Cys residue that is not present in
      other gonadotropin beta-subunits.

PMID- 7642108
TI  - Domain libraries: synthetic diversity for de novo design of antibody V-regions.
AB  - A completely synthetic gene library encoding the variable light (VL)
      immunoglobulin domains has been constructed in vitro. The library was constructed
      by assembling a set of six oligodeoxyribonucleotides (oligos) using the
      polymerase chain reaction (PCR). Three out of the six overlapping
      oligonucleotides were synthesized with randomized complementarity determining
      regions (CDR) with the codon pattern, (NNS)n, where N is any of the four
      nucleotides (nt) and n is the number of codons with variation in the CDR. The
      framework regions, taken from the D1.3 anti-lysozyme antibody (Ab), were kept
      intact. Overlapping regions of approx. 20 nt, together with two additional
      flanking primers carrying the desired restriction sites, allowed the construction
      of a library in one single PCR reaction. The VL library was cloned into the phage
      display vector pEXmide3, and ten randomly picked clones were sequenced. These
      sequences exhibited complete diversity in all the three CDR and the codons for
      five canonical amino acid (aa) residues were kept intact and identified. Seven
      clones contained the full-length gene for the VL domain while deletions were
      observed in three clones. The restricted use of nt at the third position
      successfully avoided the stop codons TGA and TAA, whereas the stop codon TAG is
      read as Gln in an amber suppressor strain. We call this synthetic Ab diversity
      Domain Library, and it represents an example of synthetic libraries with
      extensive, multiple randomized sequences. The use of Domain Libraries opens up
      the possibility for design in Ab engineering, e.g., additional CDR regions can be
      added or their length varied.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7642107
TI  - High-level expression of an altered cDNA encoding human isovaleryl-CoA
      dehydrogenase in Escherichia coli.
AB  - Isovaleryl-CoA dehydrogenase (IVD) catalyzes the conversion of isovaleryl-CoA to
      3-methylcrotonyl-CoA in the leucine catabolism pathway. The cDNA encoding the
      mature human IVD polypeptide was cloned in a prokaryotic expression vector, but
      the level of expression in Escherichia coli was extremely low and attempts to
      purify the enzyme to homogeneity were unsuccessful. To enhance expression, the
      nucleotide sequence of 22 codons within the 111-bp region at the 5'-end of the
      cDNA was altered to accommodate E. coli codon usage without altering the amino
      acid coding sequence. The altered IVD cDNA was synthesized by PCR, using a primer
      containing the desired modifications. Following overnight induction of the E.
      coli transformed with this cDNA, the enzyme was purified to homogeneity using
      diethylaminoethyl agarose and high-pressure ceramic hydroxyapatite resins. IVD
      activity was increased 165-fold in the crude extract of cells containing the
      modified cDNA, as compared to that containing the wild-type cDNA.

PMID- 7642109
TI  - Characterization of a processed pseudogene of human FAU1 on chromosome 18.
AB  - A member of the human FAU (Finkel-Biskis-Reilly murine sarcoma virus-associated
      ubiquitously expressed) gene subfamily, encoding the ribosomal protein S30 fused
      in frame to an ubiquitin-like protein, was cloned, sequenced and analysed. This
      clone, FAU1P, is a processed pseudogene with a completely intact, although
      transcriptionally silent, open reading frame of 137 codons. FAU1P exhibits an
      amplification of the (AAG) triplet repeat present in the S30 coding part of FAU.
      FAU1P is integrated in an antisense orientation within a sequence homologous to
      the promoter of the islet amyloid polypeptide (IAPP or amylin)-encoding gene. By
      means of PCR hybrid panel mapping, FAU1P was assigned to chromosome 18.

PMID- 7642110
TI  - Cell-cycle regulation of human B-myb transcription.
AB  - We demonstrate here that activity of the human B-myb promoter is regulated during
      the cell cycle by the E2 transcription factor (E2F). Comparison of the human B
      myb promoter sequence with that of its murine counterpart revealed an
      evolutionally conserved sequence that contains an E2F-binding site. In
      transiently transfected murine NIH3T3 and human HaCaT cells, luciferase (Luc)
      reporter activity directed by the human B-myb promoter was found to increase
      significantly in late G1/S phase of the cell cycle. Mutation of the promoter E2F
      site resulted in significantly greater Luc activity in NIH3T3 and HaCaT cells
      made quiescent by serum deprivation, indicating that E2F repressed transcription
      of this gene during G0. Analysis of E2F DNA-binding activity in G0 HaCaT cells
      revealed a distinct complex that apparently contained neither the retinoblastoma
      gene protein, pRb, nor the related p107 protein. De-repression of transcription
      in S phase was accompanied by the disappearance of this G0 E2F complex and the
      appearance of a distinct complex containing p107. In addition, complexes
      containing pRb were detected at both stages of the cell cycle.

PMID- 7642111
TI  - A novel expression vector composed of a regulatory element of the human
      leukosialin-encoding gene in different types of mammalian cells.
AB  - The regulatory element (RE) of the human leukosialin (LS)-encoding gene, that
      encodes a major sialoglycoprotein of human leukocyte and platelet membranes, was
      used to develop a novel expression vector, pKX. The vector was constructed by
      cloning a RE fragment and the SV40 fragment containing polyadenylation and
      splicing signals between HindIII and BamHI sites of the pCAT-Basic vector. The
      transcription level controlled by this vector was evaluated in six different cell
      lines using a transient expression assay of chloramphenicol acetyltransferase
      (CAT). The CAT activity of the pKX vector was compared to the other common
      expression vectors, namely pMSG (driven by the mouse mammary tumor virus LTR),
      pcDL-SR alpha (SV40 promoter/enhancer and HTLV-I LTR), pcDNAI (cytomegalovirus
      promoter/enhancer) and pCAT-Control (SV40 promoter/enhancer). The level of
      expression provided by the pKX vector was comparable to that observed with pcDNAI
      and pcDL-SR alpha vectors. In different mammalian cell lines, the highest
      efficiency of expression of the pKX vector was observed in the human T-cell
      lines, Jurkat and CEM, although the expression of pcDL-SR alpha-CAT in those cell
      lines was in the same range. The expression of the pKX vector driven by a non
      viral promoter and/or enhancer can be as efficient as that driven by a viral
      promoter and/or enhancer. Potential uses of this vector may be found in studies
      of transient gene expression in hematopoietic cells and for gene therapy,
      particularly the ones involving T-cells.

PMID- 7642113
TI  - Sequence comparison of three mammalian type-X collagen promoters and preliminary
      functional analysis of the human promoter.
AB  - The mechanism(s) controlling the specific expression of the type-X collagen
      (COL10A1)-encoding gene in the growth plate of developing long bones is not
      known. In preparation for identifying and characterizing the 5'-regulatory
      sequences and transcription factors which control mammalian Col10a1 gene
      expression, we have isolated and sequenced the first exon and 5' flanking
      promoter regions of bovine Col10a1. Sequence comparisons, including those
      previously published for mouse Col10a1, highlighted a number of conserved domains
      within the promoter and upstream elements. Reporter cat gene (encoding
      chloramphenicol acetyltransferase, CAT) constructs containing 5'-regulatory
      sequences of human COL10a1 (hCOL10a1) were transfected into primary cultures of
      foetal bovine growth plate chondrocytes producing COL10A1 and non-producing
      epiphyseal cartilage chondrocytes. Constructs containing up to 900 bp of promoter
      sequence exhibited low levels of CAT production in expressing cells and non
      expressing cells. Addition of a further 1.5 kb of upstream sequence resulted in a
      dramatic increase in CAT production in expressing cells only. The results
      demonstrate the presence of enhancer-like elements between 900 bp and 2.4 kb
      upstream of the transcription start point(s) of hCOL10a1, which is distinctly
      different from that reported for the chick.

PMID- 7642112
TI  - Sequence analysis of the MAGE gene family encoding human tumor-rejection
      antigens.
AB  - The MAGE multigene family, which includes the MAGE-1 and -3 genes that encode
      tumor-rejection antigens on HLA-A1 recognized by cytotoxic T-lymphocytes (CTL),
      is preferentially expressed at the mRNA level on human malignant cells, but not
      on normal cells. However, little is known about the MAGE-4, -41 and -6 genes. In
      this study, we have amplified 1040 bp (MAGE-1), 1061 bp (MAGE-3 and -6) and 1064
      bp (MAGE-4 and -41) cDNA fragments, including the entire coding sequences (927
      951 bp), using the reverse transcription-polymerase chain reaction (RT-PCR)
      method followed by nucleotide (nt) sequencing. One member had greater than 80 or
      66% homology with the other members at the nt or deduced amino acid (aa) levels,
      respectively. Higher homology was found between MAGE-3 and -6 (98% at the nt
      level) and also between MAGE-4 and -41 (98%). The results of this investigation
      demonstrated high homology, as well as the clear differences between the members
      of the MAGE family at the coding sequence level.

PMID- 7642114
TI  - Isolation of cDNAs encoding GTP cyclohydrolase II from Arabidopsis thaliana.
AB  - A GTP cyclohydrolase II-encoding gene from Arabidopsis thaliana was isolated
      through functional complementation of a mutant of Escherichia coli, BSV18,
      deficient in this protein. The derived amino-acid sequence constitutes a
      polypeptide of 27 kDa and shows 37-58% identity with previously published
      sequences of Escherichia coli, Bacillus subtilis, Photobacterium leiognathi and
      P. phosphoreum.

PMID- 7642116
TI  - Comparison between cDNA clones encoding murine DNA ligase I.
AB  - A 3172-nucleotide (nt) cDNA clone encoding mouse DNA ligase I (LigI) was isolated
      from an embryonic stem cell cDNA library. Another mouse LigI cDNA clone has been
      recently described. Six single-amino-acid alterations have been identified
      between the two mouse LigI clones.

PMID- 7642115
TI  - Isolation of a cDNA encoding a novel chicken chemokine homologous to mammalian
      macrophage inflammatory protein-1 beta.
AB  - A cDNA encoding a novel chicken chemokine homologous to mammalian chemokine
      macrophage inflammatory protein 1 beta (MIP-1 beta) was isolated and
      characterised. The cDNA encodes a protein which is 75-80% homologous to human and
      mouse MIP-1 beta. All conserved amino acids characteristic of the mammalian
      chemokine family have been evolutionarily preserved in chicken MIP-1 beta,
      suggesting similar protein folding patterns and functional properties.

PMID- 7642117
TI  - Isolation of a cDNA clone encoding mouse 3-hydroxyacyl CoA dehydrogenase.
AB  - Rae-38, a cDNA clone isolated from mouse embryonal carcinoma F9 cells, was
      sequenced, and the deduced RAE-38 protein showed about 86% homology to pig 3
      hydroxyacyl CoA dehydrogenase (HCDH; EC 1.1.1.35). This clone can be used to
      elucidate the regulatory mechanism of HCDH gene expression in mammals.

PMID- 7642118
TI  - Cloning and sequencing of cDNA encoding the cat growth hormone.
AB  - A cDNA encoding cat growth hormone (Fc GH) has been isolated and sequenced. This
      is the first report of a feline GH nucleotide and deduced amino acid (aa)
      sequences. This cat pituitary cDNA resembles a typical mammalian pre-GH cDNA with
      its encoded mature hormone differing from dog GH only by a single aa residue.

PMID- 7642119
TI  - The structure of intron 1 in the chicken growth hormone-encoding gene.
AB  - An additional PstI fragment of 197 bp was found to be present in intron 1 of the
      gene encoding chicken growth hormone which we reported previously [Tanaka et al.,
      Gene 112(1992)235-239].

PMID- 7642120
TI  - Cloning and sequence analysis of the DNA ligase-encoding gene of Rhodothermus
      marinus, and overproduction, purification and characterization of two
      thermophilic DNA ligases.
AB  - In this paper we describe the cloning and sequence analysis of a gene encoding
      DNA ligase (Lig; EC 6.5.1.2) from the thermophilic bacterium Rhodothermus marinus
      (Rm). We also describe the overexpression of the Lig-encoding genes of Rm and the
      thermophile, Thermus scotoductus (Ts), in Escherichia coli, and the purification
      and characterization of the overproduced Lig. The Rm lig gene encodes a protein
      of 712 amino acids (aa) with a calculated molecular mass of 79,487 Da. Comparison
      with published sequences of bacterial Lig revealed significant homology between
      the NAD(+)-utilizing Lig, and alignment of their aa sequences revealed several
      blocks of conserved residues. Both of the purified Lig exhibit nick-closing
      activity over a wide range of temperatures. Under our assay conditions the Rm Lig
      was active at 5-75 degrees C with apparent optimal activity above 55 degrees C.
      The Ts enzyme showed activity at 15-75 degrees C with optimal activity above 65
      degrees C. The half-life of the Lig at 91 degrees C was estimated to be 7 min for
      the Rm Lig and 26 min for the Ts Lig.

PMID- 7642121
TI  - Structure, organization and promoter expression of the actin-encoding gene in
      Trichoderma reesei.
AB  - The single gene encoding actin (Act) in the cellulolytic filamentous fungus
      Trichoderma reesei (Tr) has been isolated and characterized. The gene contains
      five introns located in identical positions when compared to the putative
      ancestral actin genes (act) present in Thermomyces lanuginosus and Aspergillus
      nidulans. The 5' untranslated region (UTR) of the gene contains a TATA-like
      sequence (TAATA), a C + T-rich region and a potential CCAAT motif. This region
      was used as a homologous promoter to direct expression of hygromycin-B-resistance
      encoding gene as a dominant-selectable Tr marker.

PMID- 7642122
TI  - Cloning and expression of a gene encoding a T-cell reactive protein from
      Coccidioides immitis: homology to 4-hydroxyphenylpyruvate dioxygenase and the
      mammalian F antigen.
AB  - The gene which encodes a previously described T-cell reactive protein (TCRP) of
      the human fungal pathogen Coccidioides immitis (Ci) was cloned and sequenced.
      Both the genomic and cDNA sequences were determined. The transcription start
      point was confirmed. The tcrP gene has three introns and a 1197-bp ORF which
      translates to a 399-amino-acid (aa) protein (45.2 kDa). The predicted protein has
      approx. 50% aa sequence identity and 70% similarity to mammalian 4
      hydroxyphenylpyruvate dioxygenase (HPPD) proteins and mammalian F-antigens.
      Expression of the Ci tcrP in Escherichia coli resulted in production of a deep
      brown pigment, consistent with E. coli expression of the bacterial HPPD homolog
      from Shewanella colwelliana. The TCRP is likely the Ci form of HPPD.

PMID- 7642123
TI  - Cloning and sequencing of the gyrA gene from the plant pathogen Erwinia
      carotovora.
AB  - The gyrA gene of Erwinia carotovora subsp. carotovora has been cloned and
      sequenced. The deduced protein possessed 86% identity with the Escherichia coli
      GyrA protein. E. carotovora gyrA was also shown to complement an E. coli gyrA43ts
      mutation.

PMID- 7642124
TI  - Structure of the ubiquitin-encoding genes of Cryptococcus neoformans.
AB  - Cryptococcus neoformans (Cn) contains two ubiquitin (UBI)-encoding genes located
      on separate chromosomes. The UBI1 gene consists of UBI fused to a 53-amino-acid
      (aa) tail and is 95% identical to the Saccharomyces cerevisiae (Sc) UBI1 which
      codes for an UBI-CEP52 ribosomal protein fusion. UBI4 is a polyubiquitin gene
      that contains five UBI repeats. The UBI4 aa sequences differ from Sc UBI by a
      single aa. UBI1 contains two introns in the UBI-encoding portion and two introns
      in the tail. Single introns are present in three of the repeats in UB14 and are
      located at the same positions as those in UBII. There was also an average of 15%
      nt differences among UBI repeats. The results provide evidence of extensive
      recombination and/or conversion events between repeated genes in Cn.

PMID- 7642125
TI  - Cloning and analysis of cDNA encoding an elongation factor 1 alpha from the
      dimorphic fungus Histoplasma capsulatum.
AB  - The cDNA encoding translation elongation factor 1 alpha (EF-1 alpha) was isolated
      from the dimorphic fungus, Histoplasma capsulatum (Hc), an important pathogen of
      man. A cDNA library was probed with the tef1 gene from the fungus Mucor
      racemosus. Ten independent clones were isolated, all with similar restriction
      patterns. The longest clone (1.96 kb) was sequenced. Southern blot analysis
      revealed that the Hc tef1 gene was present as a single copy. A single transcript
      of approx. 2300 nucleotides was found in total RNA from both the yeast and mold
      forms of the organism. Comparison of the deduced 460-amino-acid Hc EF-1 alpha
      protein to EF-1 alpha proteins from other species of fungi revealed the greatest
      degree of similarity to proteins from the filamentous ascomycetes Podospora
      anserina and Trichoderma reesei. Phylogenetic tree analysis of fungal tef genes
      indicated that Hc is most closely related to filamentous ascomycetes and most
      distantly related to the budding yeast Saccharomyces cerevisiae.

PMID- 7642126
TI  - Primary structure and partial characterization of a life-cycle-regulated cysteine
      protease from Trypanosoma (Nannomonas) congolense.
AB  - Trypanosoma (Nannomonas) congolense is an important pathogenic parasite of
      domestic livestock in Africa. We have cloned a cDNA encoding a prepro-cysteine
      protease of this protozoan, the sequence of which indicates it is an early mRNA
      processing intermediate. Northern analysis demonstrates a life-cycle-stage
      specificity similar to previously described enzymatic data. The deduced amino
      acid sequence shows extensive similarity to cysteine proteases of other parasitic
      protozoa, as well as papain and cathepsin L. As with other African trypanosomes,
      a poly-proline tract connects the catalytic domain with an unusual C-terminal
      extension.

PMID- 7642127
TI  - Unexpected diversity in U6 snRNA sequences from trypanosomatids.
AB  - We have isolated and sequenced the genes for the trans-spliceosomal U6 small
      nuclear RNAs (snRNAs) from the trypanosomatid species Leishmania mexicana (Lm)
      and Phytomonas sp. (Ps). Compared with the Trypanosoma brucei (Tb) U6 snRNA, the
      Lm U6 snRNA contains only a single additional G-C bp in the 5' terminal stem
      loop. In contrast, the Ps U6 snRNA sequence contains a G-->C change at the last
      nucleotide of the highly conserved and functionally important ACAGAG
      hexanucleotide and three additional changes in conserved positions. Our results
      indicate that trans-spliceosomal U6 snRNAs from trypanosomatid species do not
      always conform to the consensus sequence of cis-spliceosomal U6 snRNAs.

PMID- 7642128
TI  - Introduction of the octanucleotide restriction site SwaI into the bicistronic
      vector pTiSDT for high level synthesis of proteins.
AB  - The octanucleotide recognition site for the endonuclease SwaI was introduced into
      the Escherichia coli bicistronic expression vector pTiSDT by mutating a single
      position in the coupling SD sequence between a truncated form of the cro-gene and
      the multicloning site. This mutation does not influence the expression rate. The
      introduction of this restriction site allows high level production of proteins,
      that are modified only by an N-terminal methionine incorporated as the start
      codon.

PMID- 7642129
TI  - The cellulase complex of Neurospora crassa: cbh-1 cloning, sequencing and
      homologies.
AB  - We describe the isolation, cloning and sequencing of the cellobiohydrolase 1 (EC
      3.2.1.91)-encoding gene (cbh-1) of Neurospora crassa. The nucleotide and amino
      acid sequences have high homology with the cbh-1 of Trichoderma reesei, Humicola
      grisea and Phanerochaete chrysosporium, with clear signal, catalytic, hinge and
      substrate-binding domains in that order.

PMID- 7642130
TI  - Aliphatic nitrilase from a soil-isolated Comamonas testosteroni sp.: gene cloning
      and overexpression, purification and primary structure.
AB  - An aliphatic nitrilase, active on adiponitrile and cyanovaleric acid, was
      identified and purified from Comamonas testosteroni sp. (Ct).
      Oligodeoxyribonucleotide probes were designed from limited amino acid (aa)
      sequence information and used to clone the corresponding gene, named nitA. High
      homologies were found at the aa level between Ct nitrilase and the sequences of
      known nitrilases. Multi-alignment of sequenced nitrilases suggests that Cys163 of
      Ct plays an essential role in the active site. This hypothesis is strengthened by
      molecular studies on nitrilases from Alcaligenes faecalis JM3, and Rhodococcus
      rhodochrous J1 and K22 [Kobayashi et al., Proc. Natl. Acad. Sci. USA 90 (1993)
      247-251; J. Biol. Chem. 267 (1992) 20746-20751; Biochemistry 31 (1992) 9000
      9007]. Large amounts of an active recombinant enzyme could be produced in
      Escherichia coli when nitA was overexpressed together with the E. coli groESL
      genes.

PMID- 7642131
TI  - Identification of fimbrial assembly genes from Dichelobacter nodosus: evidence
      that fimP encodes the type-IV prepilin peptidase.
AB  - Dichelobacter nodosus (Dn) is the causative agent of footrot, an economically
      significant disease of sheep. One of the factors believed to be involved in the
      virulence of this organism is its ability to produce type-IV fimbriae, which are
      the major protective antigens. To investigate the process of fimbrial biogenesis
      in Dn, gene probes were constructed from pilus biogenesis genes of Pseudomonas
      aeruginosa (Pa) and used to isolate homologues from Dn. A homologue, designated
      fimP, of the Pa prepilin peptidase-encoding gene, pilD, was cloned using this
      approach. The fimP gene product was shown to possess endopeptidase activity when
      produced in Escherichia coli. Two other fimbrial biogenesis genes fimN and fimO,
      whose products show similarity to the Pa PilB and PilC proteins, respectively,
      were identified because of their linkage to fimP. The arrangement of fimN, fimO
      and fimP in Dn closely resembles the arrangement of pilB, pilC and pilD in Pa.

PMID- 7642132
TI  - Rhizobium leguminosarum NodT is related to a family of outer-membrane transport
      proteins that includes TolC, PrtF, CyaE and AprF.
AB  - Cells containing a protein fusion consisting of the Rhizobium leguminosarum bv.
      viciae nodulation protein, NodT, fused to PhoA, produced alkaline phosphatase
      activity, indicating that the N terminus of NodT could translocate PhoA across
      the inner membrane. Cellular fractionation suggested that the NodT::PhoA fusion
      is targetted to the outer membrane. NodT resembles a family of bacterial outer
      membrane proteins including TolC, PrtF, CyaE and AprF, which are involved in
      secretion. By analogy, NodT (together with the inner membrane putative transport
      proteins NodI and NodJ) is proposed to be involved in the secretion of nodulation
      factors.

PMID- 7642133
TI  - Identification and activity of two insertion sequence elements in Rhodococcus sp.
      strain IGTS8.
AB  - Two putative insertion sequence (IS) elements, IS1166 and IS1295, were identified
      on a plasmid present in Rhodococcus sp. IGTS8. Four copies of IS1166 were present
      in strain IGTS8: one copy on each of two separate plasmids and two copies on a
      third plasmid or in the chromosome. Of eight rhodococci tested, only R. zopfii
      contained a copy of an IS1166-like element. Two mutants of strain IGTS8 were
      isolated in which an additional copy of IS1166 was present, suggesting that at
      least one copy of this element may be able to transpose. IS1166 and IS1295 are
      new members of a family of IS elements which includes IS6120 from Mycobacterium
      smegmatis, IST2 from Thiobacillus ferrooxidans, IS256 from Staphylococcus aureus
      and ISRm3 from Rhizobium meliloti. The 24-25-bp inverted repeats of these six
      elements are highly similar and, with the exception of IS1295, their transposases
      exhibit moderate identities. In particular, the predicted amino-acid sequence of
      the transposase from IS1166 is 86% identical to that from the known transposable
      element IS6120.

PMID- 7642134
TI  - Characterization of the Pasteurella multocida skp and firA genes.
AB  - A 2.9-kb fragment of the Pasteurella multocida (Pm) genome encoding proteins p25
      (25 kDa) and p28 (28 kDa) has previously been cloned and expressed in Escherichia
      coli (Ec). In the present paper, the nucleotide (nt) sequence of a 1.8-kb
      subfragment encoding the two proteins is described. The cloned fragment contains
      three open reading frames (ORFs). ORF1 is incomplete. ORF2 is homologous to the
      skp gene of Ec. ORF3 overlaps ORF2 and is highly homologous to the firA gene of
      Ec. The skp and firA genes are part of an operon governing the first steps of
      lipid A synthesis. Comparing the nt sequence with the N-terminal sequences of p25
      and p28 revealed that the two proteins are encoded by ORF2 (skp). The preprotein
      p28 is converted into p25 by cleavage of a 23-amino-acid leader peptide. Though
      it serologically cross-reacts with porin H of Pm, p25 is not related to known
      bacterial porins.

PMID- 7642135
TI  - Efficient secretion of Bacillus subtilis levanase by Saccharomyces cerevisiae.
AB  - The secretion of Bacillus subtilis (Bs) levanase (Lev) was studied in the yeast
      Saccharomyces cerevisiae. A set of different yeast expression plasmids, based on
      the constitutive PGK promoter and harbouring the Bs Lev-encoding gene (sacC), was
      constructed. In these plasmids, the original Bs signal sequence was either
      intact, partially deleted or entirely missing. With all constructs, Lev was
      produced from yeast transformants. However, only when the intact bacterial signal
      peptide was present was the synthesized enzyme secreted; around 20% was found in
      the periplasm and 30% in the culture medium. The secreted protein found in the
      periplasmic space was mainly core-glycosylated and unglycosylated, and had a size
      of 80-90 and 74 kDa, respectively. In contrast, Lev found in the culture medium
      was mainly hyper-glycosylated and had a size of 180-200 kDa. Yeast transformants
      harbouring sacC, but lacking parts of the bacterial signal sequence, only
      produced cytoplasmic protein which was not glycosylated and had a size of about
      74 kDa. The deletion of the entire signal peptide and a further 22 amino acids at
      the N terminus of mature Lev resulted in a 71-kDa cytoplasmic protein which was
      not active.

PMID- 7642136
TI  - Bacillus subtilis glnR mutants defective in regulation.
AB  - The Bacillus subtilis glnR gene (part of the glnRA operon) encodes a 135-amino
      acid (aa) repressor, GlnR, that regulates glnRA transcription in response to
      nitrogen levels in the growth medium. Two glnR mutants unable to repress under
      nitrogen excess conditions were obtained by mutagenesis. Lesions were found at
      Leu77 and Ala80, aa that lie within a region (between aa 59-83) thought to form
      the alpha-helix-turn-alpha-helix (HTH) motif common among a class of regulatory
      proteins. Alteration of Gly72 by site-directed mutagenesis also affected
      regulation, suggesting that aa within the putative HTH region are critical for
      GlnR function and may be involved in DNA binding. However, other replacements
      within the aa 59-83 sequence failed to support the HTH structure proposed for
      this region. Mutations within the C-terminal region of GlnR were also found to
      affect regulation. Introduction of an ochre stop codon at aa 110, 116, 123 and
      129 resulted in the production of truncated proteins that were constitutively
      repressed, strongly suggesting that a signal recognition site residues within the
      last seven aa of GlnR. Substituting Asp129 with Asn led to loss of repression,
      indicating that Asp129 may be directly involved in interacting with either
      positive or negative effector molecules, or is a target for post-translational
      modification.

PMID- 7642137
TI  - Cloning and characterization of the cytotoxin L-encoding gene of Clostridium
      sordellii: homology with Clostridium difficile cytotoxin B.
AB  - Hybridization of an oligodeoxyribonucleotide (oligo) probe, designed from a
      repeated sequence ('oligo rep') at the C terminus of the Clostridium difficile
      (Cd) cytotoxin (Cyt), revealed that homologies exist between the Cd cyt gene and
      the genomes of several other clostridia, including Clostridium sordellii (Cs),
      suggesting a common ancestral cyt amongst the Clostridium genus. This Cd 'oligo
      rep' probe was used to clone the Cs (strain 6018) cyt. The sequenced (7095 bp)
      region encodes 2364 amino acids (aa) and corresponds to a protein of 270,614 Da.
      Cs Cyt has 76% identity with the Cd Cyt and 47% identity with the Cd enterotoxin
      (Ent). The latter third of the protein consists of repeated units, similar to
      those found for Cd Cyt. A highly conserved hydrophobic domain can be delineated.
      Few structural differences are evident between Cd and Cs Cyt to explain their
      different cellular and sub-cellular effects. A small open reading frame (ORF)
      encoding a protein of 16,484 Da is located 210 bp downstream from cyt. No
      homology was evident with any known sequence. The first 30 aa of this ORF may
      correspond to a signal peptide.

PMID- 7642138
TI  - Sequences of nifX, nifW, nifZ, nifB and two ORF in the Frankia nitrogen fixation
      gene cluster.
AB  - The actinomycete Frankia alni fixes N2 in root nodules of several non-leguminous
      plants. It is one of the few known N2-fixing members of the high-GC Gram+ lineage
      of prokaryotes. Thus, we have undertaken a study of its nitrogen fixation gene
      (nif) organization to compare with that of the more extensively characterized
      proteobacteria. A cosmid (pFN1) containing the nif region of Fa CpI1 was isolated
      from a cosmid library using the nifHDK genes of Fa CpI1 as a probe. A 4.5-kb
      BamHI fragment that mapped downstream from the previously characterized nifHDK
      genes was cloned and sequenced. Based on nt and aa sequence similarities to nif
      from other N2-fixing bacteria, eight ORF were identified and designated nifX,
      orf3, orf1, nifW, nifZ, nifB, orf2 and nifU. A region that hybridized to
      Rhizobium meliloti and Klebsiella pneumoniae nifA did not appear to contain a
      nifA-like gene. We have revised the map of the Fa nif region to reflect current
      information.

PMID- 7642139
TI  - Identification of a fliG homologue in Treponema denticola.
AB  - Using a bacteriophage lambda library of Treponema denticola (Td) ATCC 35405 DNA,
      and, as a reagent, sera derived from individuals with advanced adult periodontal
      disease, a variety of recombinant clones producing antigens of this oral
      spirochete have been isolated. Nucleotide sequence analysis of a clone expressing
      three immunoreactive antigens has revealed the presence of an open reading frame
      highly homologous to the flagellar switch/motor protein, FliG, which is known to
      be essential for flagellar assembly and rotation, and chemotaxis in enteric
      bacteria. The deduced amino-acid sequence of the treponemal FliG protein had 73%
      similarity (55% identity) to the Bacillus subtilis FliG protein, and showed
      significant, but lesser homologies to Gram- FliG proteins. Sequence analysis of
      regions flanking fliG indicated that this gene is immediately preceded by a fliF
      homologue, further supporting that the cloned DNA encodes FliG of Td. The
      findings imply that although the signals for control of chemotaxis may be
      distinctly different in spirochetes, at least some of the molecules involved in
      torque generation, control of flagellar rotation and signal transduction are
      highly conserved with other bacteria. The stronger homology of the spirochete
      FliG with those of Gram+ bacteria is also consistent with recent analyses of
      other spirochetal genes.

PMID- 7642140
TI  - Autophosphorylation and activation of transcriptional activator PhoB of
      Escherichia coli by acetyl phosphate in vitro.
AB  - The PhoB protein, the transcriptional activator for the genes belonging to the
      phosphate regulon in Escherichia coli, was autophosphorylated in the presence of
      acetyl phosphate (acP) in vitro. The properties of phospho-PhoB, such as
      stability upon acid or alkali treatment and activating pstS transcription by RNA
      polymerase holoenzyme, were the same as those of phospho-PhoB produced from
      phospho-PhoR or phospho-PhoM. These results indicate that PhoB is an enzyme that
      catalyzes its own phosphorylation using acP, a low-molecular-weight metabolic
      intermediate.

PMID- 7642141
TI  - Carbon source-dependent regulation of the acetyl-coenzyme A synthetase-encoding
      gene ACS1 from Saccharomyces cerevisiae.
AB  - The yeast ACS1 gene, encoding acetyl-coenzyme A synthetase (ACS), was cloned
      using colony hybridization and a facA probe from Aspergillus nidulans. The
      complete sequence of 1.5 kb of the ACS1 upstream region was determined. Northern
      hybridization revealed a strong depression of ACS1 transcripts in a strain grown
      on the nonfermentable carbon sources, acetate or ethanol. In contrast to a
      previous report, delta acs1 null mutants did not exhibit a growth defect on
      acetate medium. Indeed, enzyme assays showed the presence of an additional
      constitutively expressed ACS activity in delta acs1 mutants. The carbon source
      dependent expression was further investigated by the use of an ACS1::lacZ fusion
      gene, showing complete repression on easily fermentable sugars such as glucose,
      maltose, sucrose or galactose. Binding sites for the yeast general regulatory
      factors, Abf1p and Reb1p, together with a sequence reminiscent of the recently
      identified carbon source-responsive element (CSRE), could be detected in the ACS1
      upstream region, presumably mediating the observed regulatory phenotype of this
      ACS isoenzyme.

PMID- 7642142
TI  - Cloning and characterization of the adenine phosphoribosyltransferase-encoding
      gene (APT1) from Saccharomyces cerevisiae.
AB  - We have cloned, sequenced and characterized the APT1 (adenine
      phosphoribosyltransferase) gene from Saccharomyces cerevisiae. The APT1 sequence
      includes an open reading frame encoding 221 amino acids and is contained within a
      1322-bp insert that complements APRT-deficient mutants to wild-type levels of
      enzyme activity. Analysis by primer extension revealed multiple transcription
      start points (tsp) and a major tsp 21-bp upstream from the ATG start codon. A
      transcript initiated at the major tsp would yield a 700-nt mRNA which is in
      agreement with the size observed by Northern analysis. Sequence comparison
      indicates that the yeast enzyme shares strong similarities with other known APRT
      of bacterial, invertebrate, plant and mammalian origins.

PMID- 7642143
TI  - Recombinant histatins: functional domain duplication enhances candidacidal
      activity.
AB  - Histatin 3 (Hst3) is a 32-amino-acid (aa) His-rich protein with antimicrobial
      activity found in human salivary secretions. To explore further the
      structure/function relationship of Hst, we utilized a bacterial system for the
      efficient production of recombinant Hst3 (re-Hst3) and Hst variants. Previously,
      we demonstrated that the middle portion of Hst3 (aa 13-24) contains the
      functional domain responsible for killing Candida albicans. Using PCR and splice
      overlap extension, a Hst variant (re-Hst3rep) was made in which the functional
      domain was repeated in tandem. Using the pRSET bacterial expression system, re
      Hst3 and the variant re-Hst3rep were produced as chimeric fusions and were
      isolated from bacterial sonicates by affinity chromatography. Affinity purified
      fusion proteins were digested with CNBr and re-Hst were separated from their
      fusion partners by reverse-phase high-performance liquid chromatography. The
      activity of re-Hst3 and re-Hst3rep was compared to that of native Hst3 from human
      salivary secretions in the C. albicans killing assay. The LD50 values for
      candidacidal activity of native Hst3, re-Hst3 and re-Hst3rep were 7.2, 6.8 and
      4.1 nmol/ml, respectively. At lower concentrations re-Hst3rep was five times more
      active than native Hst3 or re-Hst3 and at even lower concentrations re-Hst3rep
      exhibited significant candidacidal activity while native Hst3 and re-Hst3 were
      inactive. These results demonstrate an expression system for production of
      biologically active functional Hst and Hst variants and shows that repetition of
      the functional domain of Hst3 enhances candidacidal activity.

PMID- 7642144
TI  - A K-252a-resistance gene, sks1+, encodes a protein similar to the Caenorhabditis
      elegans F37 A4.5 gene product and confers multidrug resistance in
      Schizosaccharomyces pombe.
AB  - A gene named sks1+ was cloned as a suppressor of the K-252a-sensitivity phenotype
      of Schizosaccharomyces pombe (Sp) from a gene library of the parental Sp
      chromosomal DNA constructed with a multicopy vector pDB248'. The gene encoded a
      308-amino-acid (aa) protein similar to the Caenorhabditis elegans F37 A4.5 gene
      product and to the mouse and Drosophila Mov34 gene products. The sks1+ null
      mutants obtained by gene disruption were non-viable, indicating that sks1+ is
      essential for vegetative growth. The parental Sp strain carrying multiple copies
      of sks1+ showed distinct cross-resistance to staurosporine, thiabendazole and
      vanadate in addition to K-252a, although Sks1 has no similarity in aa sequence to
      those of ATP-binding cassette (ABC)-type transporters. The multicopy plasmid
      containing sks1+ conferred multidrug resistance (MDR), even in a mutant cell
      defective in pmd1+ encoding an ABC-type transporter. It is therefore unlikely
      that the function of pmd1+ is involved in MDR conferred by sks1+. These results
      suggest that sks1+ is a functionally novel MDR gene.

PMID- 7642145
TI  - Isolation and characterization of SpTRK, a gene from Schizosaccharomyces pombe
      predicted to encode a K+ transporter protein.
AB  - A novel gene, SpTRK, has been isolated from DNA of the fission yeast
      Schizosaccharomyces pombe (Sp) by hybridization to an oligodeoxyribonucleotide
      (oligo) probe designed from a sequence fully conserved between the potassium
      transporter genes TRK1 and TRK2 of Saccharomyces cerevisiae (Sc). SpTRK is a
      single-copy gene located on Sp chromosome I. Nucleotide sequence analysis of the
      cloned gene identified an open reading frame (ORF) with coding capacity for a
      protein of 833 amino acids (aa). The predicted SpTRK aa sequence showed a high
      level of conservation relative to the potassium transporters of Sc and
      Saccharomyces uvarum (Su), particularly within their transmembrane (TM) domains
      and in aa required for their ion transport functions. A single SpTRK transcript
      of about 2.7 kb is expressed at high levels in exponentially growing Sp cells,
      but it is downregulated in cells from stationary cultures.

PMID- 7642146
TI  - [Non-puerperal mastitis. Clinical study of 30 patients].
AB  - Non puerperal mastitis is an inflammatory disease that resembles carcinoma, the
      course is insidious and frequently this entity is misdiagnosed. The recurrence
      has been reported until 60%. This report is a prospective clinical investigation,
      of 30 patients with diagnosis of periductal mastitis, in these women were
      analyzed; age, marital stage, deliveries, breast feeding symptoms like tumour,
      inflammatory signs, mammary ductal fistula, mamography, cytology, bacteriology,
      histopathology, medical and surgical treatment. The middle age was 36 years old,
      70% between 30 and 50 years old, 26 patients were multiparous, breast feeding
      were mentioned for 20 women. The tumor was palpable 70% of the cases, localized
      preferentially in the retroareolar segment, inflammatory changes were observed in
      25 cases, 19 patients with fistula. The cytology was negative in 13 cases. In the
      bacterial culture were isolated, Staphylococcus aureus in 7 cases, Proteus
      vulgaris in 2 cases and seven cases resulted negative. Mamographic exams were
      realized in 23 patients; one case resulted adenocarcinoma. The medical treatment
      were with Eritromycin and Metronidazol and then, ducts resection surgery were
      performed in 16 cases, one case with adenocarcinoma was performed a modified
      radical mastectomy. The results were satisfactory 22 women improved, 6 cases with
      recurrence and two cases with spontaneous improvement.

PMID- 7642147
TI  - [Obstetric hysterectomy. Concept and importance].
AB  - Genital hemorrhage continues to be the primary cause of death among fertile
      women. Hysterectomy, when practiced as a second surgical procedure following an
      obstetric event, and without having been planned, is an ongoing therapeutic
      resource. The author depicts the risk profile of women who could eventually
      undergo obstetric hysterectomy. Certain pathologies, guidelines, surgical
      technique instructions, and other surgical manouvers are also presented. The
      causes of surgical re-intervention and other surgical techniques, as well as
      massive blood loss, and morbidity are assessed. The authors finally emphasize the
      importance of an early consultation, of a correct surgical technique, the
      appropriate equipment management, and the measures for preventing the originating
      pathology.

PMID- 7642148
TI  - [Anesthesia for severe genital hemorrhage].
AB  - Severe genital hemorrhage is one of the three leading causes of death in gyneco
      obstetrics and oncology. Since this problem is a surgical emergency leaving no
      room for delay, the causes for this phenomenon are analysed in this paper,
      stressing the importance of detection and clinical assessment in order to
      determine the effective and immediate type of corrective surgical procedure. The
      principal objective is to specify the role of the anesthesiologist during the
      patient's preoperative, transoperative and postoperative periods. Some general
      and some specific recommendations are made with regards to the selection of the
      anesthetic technique depending on the degree of hemorrhage and the type of
      operation later to be performed. Finally, the criteria for two types of therapy
      are presented: blood transfusion therapy (and the transfusion of blood
      components) and hydroelectrolytic therapy, in which the anesthesiologist and the
      internist perform an essential role in the intensive care units, the latter being
      the ideal site for postoperative management.

PMID- 7642150
TI  - [Autoimmune thrombocytopenia and pregnancy].
AB  - Autoimmune thrombocytopenic purpura PTA, occurs more commonly in women during the
      reproductive years. Consequently, physicians frequently must manage pregnant
      patients with PTA. The management of the mother is simplified because an
      important measure of platelet count, is readily available. However the management
      of the fetus is more difficult because no definitive maternal treatment to
      prevent fetal thrombocytopenia has been successful. The performance of
      percutaneous umbilical blood sampling or fetal scalp sampling allow the
      determination of fetal platelet before delivery. If a fetal thrombocytopenia of
      less than 50,000 mm3 is detected, cesarean section is indicated to avoid
      intracranial hemorrhage in the fetus.

PMID- 7642149
TI  - [Urethral leiomyoma during pregnancy. Report of a case and review of the
      literature].
AB  - We present a case of leiomyoma of the urethra diagnosed during pregnancy. The
      patient a 40 year old woman, gravida II, who presents a mass that depend of the
      proximal urethra, it was observed in the vaginal introitus, it's growth was
      progressive after 8th weeks of pregnancy. We realized local excision at 23rd
      weeks pregnancy. Histopathological examination reported leiomyoma of the urethra.
      The pregnancy was resolved through cesarean section by fetal indication. Actually
      the patient is free of symptoms.

PMID- 7642151
TI  - [Hemodynamic and metabolic approach in severe genital hemorrhage].
AB  - Severe genital hemorrhage in women is almost always present during puerperal
      pregnancy status. Thus, bearing in mind the hemodynamic and metabolic changes
      which appear physiologically during gestation: hypovolimia, hemodilution,
      tachycardia, and modification showing in blood coagulation factors and in
      electrocardiogram, is of paramount importance. In this article, a four-type
      genital bleeding classification based on the extent of blood loss is presented.
      Out of the four types. Class III and class IV correspond to hypovolemic shock and
      call for intensive care. The need for the availability of all necessary material
      resources and the participation of a multidisciplinary team are emphasized. The
      author also emphasized the preservation of the fetus' life-while inside the
      uterus-whenever this be feasible.

PMID- 7642152
TI  - [Ehlers-Danlos syndrome in pregnancy. Report of a case and review of the
      literature].
AB  - The Ehlers Danlos Syndrome is a hereditary alteration of connective tissue,
      characterized by hyperelastic joints, tissues, and skin. The papers about the
      obstetric and gynecological aspects of Ehlers Danlos syndrome is mostly
      anecdotical and much has not originated from obstetricians and gynecologists. The
      complications are important for the feto-material binomial. The case presented
      here is related with a 39.1 of gestation associated with Ehlers Danlos syndrome,
      and a description of antenatal period, labor and delivery is done. Literature
      revision and possible relation with obstetrical care and pregnancy resolution in
      commented.

PMID- 7642153
TI  - [Is radiotherapy necessary in the control of colorectal cancer?].
AB  - Between 1966 and 1983 we selected 209 patients with colorectal adenocarcinomas,
      stage B (14%) and C (86%) of Dukes, treated with convenient surgery in 100% of
      cases, 5-fluorouracil in 85% and postoperative radiotherapy with telecobalt in
      46.41% of cases, doses of 5000 to 5500 cGy in 25 to 30 fractions. The results at
      five years postsurgery were: colon patients who received radiotherapy obtained a
      survival rate of 34 months versus 17 months for those who did not receive
      radiotherapy; rectum patients who received radiotherapy survival rate of 20
      months versus 26 months for those who did not received. Local recurrences in
      patients who received radiotherapy were 9.30% for carcinomas of the colon and
      11.53% for those with cancer of the rectum, and in patients who did not received
      radiotherapy local recurrences were 22.22% for those with cancer of the colon and
      37.83% for those with cancer of the rectum.

PMID- 7642154
TI  - [Radio-somatomedins. III. Ovarian growth factor. Its clinical use].
AB  - We label ovaric growth factor (OGF) with Iodine-131 and probed its distribution
      in experimental mouse with radiopharmacology, toxicology and genetical test with
      encouraging results. The next step was its distribution in human volunteers and
      ovarian cancer. The new radiopharmaco have high concentration in ovarian cancer;
      that make possible its scan visualization "in vivo" for diagnoses and its
      internal radiation treatment without collateral or adverse effects in 6 month of
      follow-up (clinical and laboratorial) of the volunteers and patients in where the
      new radiopharmaco was probed.

PMID- 7642155
TI  - [Presentation of the Salas obstetrical forceps (Forceps Salas)].
AB  - In the magazine of Gineco Obstetricia de Mexico, January 1988, 30 to 34, I
      presented the three first models of the Salas forceps. In this article I describe
      the fourth and last design of my invention which has been patented in the USA as
      "Salas Obstetric Spatulas". It is mentioned in this article, the advantages of
      this instrument, which after being used in 533 applications by Dr. Fernandez del
      Castillo, SC and Dr. Viesca, MA they have come to the conclusion that the Salas
      instrument is excellent. Laufe et al in his book describe: There is no doubt that
      these forceps (Salas) could be made more acceptable to US practitioners. It is
      insisted in the modern classification of the forceps.

PMID- 7642156
TI  - [Intensive prenatal diagnosis in HIV seropositivity is obsolete. Prenatal care-
      labor--puerperium].

PMID- 7642157
TI  - [30 years mitral valve prolapse--what has stayed the same?].
AB  - As a Result of echocardiographic diagnostic criteria that took too little account
      of underlying pathology, mitral valve prolapse has, in the past, been diagnosed
      far too frequently, and has been associated with commonly occurring unspecific
      symptoms (mitral valve prolapse syndrome). The results of epidemiological studies
      have led to a new definition of diagnostic criteria. The diagnosis mitral valve
      prolapse is established in the first instance by auscultation. Echocardiography
      supports the diagnosis, provides information about the prognosis, and, with a
      high level of reliability, detects complications. Major complications of this
      condition are endocarditis and mitral valve insufficiency, as also--less well
      documented--cerebral embolism and sudden heart death. Particularly at risk of
      developing complications are those patients with a systolic murmur reflecting an
      already present mitral valve insufficiency. This patient group must be monitored
      for progressive mitral insufficiency and, in the presence of relevant exposure,
      requires endocarditis prophylaxis.

PMID- 7642158
TI  - [Mitral valve prolapse--responsibilities of the family physician].

PMID- 7642159
TI  - [Responsibilities and importance of autopsy. Notification and behavior toward
      responsible parties--4].

PMID- 7642160
TI  - [Nutrition and cancer. Nutrition-associated risk for the development of various
      malignancies].
AB  - A scientific assessment of dietary risks encounters great difficulties, since
      reliable prospective studies are hardly possible, and the various forms of
      retrospective studies are associated with considerable error probabilities.
      Nevertheless, on the basis of the similar results obtained with numerous
      investigations, it is possible to make statements about definite or potential
      risks. Thus, the correlation between high levels of dietary fat and meat and
      colorectal cancer, and that between high levels of fat and mammary carcinoma,
      have been adequately demonstrated. Alcohol is a proven risk factor for numerous
      carcinomas of the gastrointestinal tract, in particular for tumors of the
      oropharynx and larynx, the esophagus and liver. But it may also be a possible
      risk factor for breast cancer and other gynecological tumors. Conversely, with
      respect to protective factors it is accepted that what is generally recognized to
      be a healthy diet (fruit, vegetables, fiber) can apparently offer a certain
      degree of protection from malignant disease.

PMID- 7642161
TI  - [Dermatomycoses. 2: Dermatomycoses of the hands].

PMID- 7642162
TI  - Histochemical localization of carbonic anhydrase in the rat duodenal epithelium.
AB  - Rat duodenum was examined for light and electron microscopical localization of
      carbonic anhydrase (CA) activity by the histochemical Hansson's method. The
      absorptive epithelial cells and some goblet cells showed a distinct reaction for
      CA activity in the cytoplasm, and on the striated borders and lateral cell
      borders. Electron microscopy confirmed that the reaction precipitates for CA
      activity are intimately associated with the cytoplasmic side of the cell
      membranes on both the lateral cell infoldings and the microvilli composing the
      brush borders. But the epithelial cells on the crypts were not positive except
      for some unidentified cells which show the distinct reaction. The duodenum was
      divided into four segments from the proximal to the distal part, and the
      homogenized mucosa scraped from each segment were examined for CA activity by
      Maren's physiological method. It was found that the activity decreased from the
      proximal to the distal segments. The most proximal segment showed the highest
      activity, 10.4 +/- 2.1 UA/mg of protein and 1468.7 +/- 324.8 UA/g of wet weight,
      and the most distal segment of duodenum showed the lowest activity, 2.4 +/- 0.7
      UA/mg of protein and 291.7 +/- 85.8 UA/g of wet weight. The significance of the
      localization of CA activity in the villous epithelium of rat duodenum was
      discussed in relation to the bicarbonate section.

PMID- 7642163
TI  - Comparison of kinetic property between human seminal and renal gamma
      glutamyltransferase.
AB  - The initial-velocity kinetics, optimal pH, acceptor specificity and the influence
      of metal ions, EDTA and urea were studied on the human seminal gamma
      glytamyltransferase (GGT) in comparison with the human renal GGT. The activity
      was measured with glycylglycine as an acceptor and with gamma-glutamyl-4
      nitroanilide or gamma-glutamyl-3-carboxy-4-nitroanilide as a donor. Because the
      double-reciprocal plots showed paralled lines, the reaction of seminal GGT
      proceeds in nonsequence (Ping Pong Bi Bi) mechanism. The acceptor Michaelis
      constants for the seminal GGT were about 2 times higher than those for the renal
      enzyme with gamma-glutamyl-3-carboxy-4-nitroanilide as well as gamma-glutamyl-4
      nitroanilide as donors, which the donor michaelis constants for seminal GGT were
      very similar to those for renal enzyme. The optimal pH and pK values were 8.2-8.6
      and about 7.7, respectively. There was little difference in the specificity for
      various acceptors between the seminal and renal enzyme. Glycylglycylglycine was
      an effective acceptor other than glycylglycine, showing 80% of the activity with
      glycylgycine. Various substrates including metal ions tested were practically
      neither inhibitory nor stimulatory for seminal and renal GGTs.

PMID- 7642164
TI  - Storage and analysis of Goldmann's visual fields with a personal computer.
AB  - A method of storing and analyzing Goldmann's visual fields with a personal
      computer has been developed and applied to cases of retinal detachment. Original
      two-dimensional analogue data, obtained manually by ophthalmologists, were
      digitized and transferred to a personal computer. A one-megabyte floppy disk was
      able to store data of 170 charts. Stored data were easily displayed on the CRT of
      the computer using two- and three-dimensional graphics. Total and four quadrant
      areas surrounded by isopter curves were calculated for fellow eyes, diseased eyes
      and operated eyes. Furthermore, weighted areas with four types of weighting
      function which attach more importance to the center than the periphery of a
      visual field were calculated. Power type weighting function was found to give the
      most significant effect on emphasizing abnormality of eyes with retinal
      detachment.

PMID- 7642165
TI  - Six cases of heterochronous gastrointestinal cancer preceded by breast cancer.
AB  - Among 432 women with primary breast cancer, six (1.4%) were diagnosed as having
      gastrointestinal cancer more than six months after operation for the breast
      cancer. This paper presents these six cases. The patients ranged from 56 to 78
      years of age at the time of breast cancer surgery, and the interval after surgery
      until diagnosis of the second cancer ranged from 7 months to 5 years 1 month. The
      second cancer was gastric cancer in 3, esophageal cancer in 2, and hepatic cancer
      in 1. All of the 6 patients had received postoperative adjuvant chemotherapy for
      breast cancer. The most frequent histological type of breast cancer was solid
      tubular carcinoma (3 patients). Three patients died, due to the second cancer, 4
      days, 2 months, and 6 months, respectively, after diagnosis of the second cancer,
      and the other patients are alive 2, 3, and 4 years after diagnosis. The Japanese
      literature regarding multiple cancer among breast cancer patients is reviewed. It
      is concluded that care should be taken to examine breast cancer patients with
      gastrointestinal symptoms, which are likely to be dismissed as a side effect of
      postoperative chemotherapy.

PMID- 7642166
TI  - A case of lymphoblastic lymphoma with aberrant morphologic feature.
AB  - We report a case of 33-year-old Japanese female who had B-cell lymphoblastic
      lymphoma with Burkitt's lymphoma (BL)-like morphologic feature. Both breasts were
      involved and the resected tissue showed starry sky macrophages and a
      proliferation of lymphoblasts containing lipid droplets. The nucleus of the
      lymphoblast was oval or indented. The neoplastic cells examined expressed TdT,
      CD10, CD14, CD38, and WH14 (a marker of pre-B cell leukemia/lymphomas). Southern
      blotting analysis showed a rearrangement of the immunoglobulin heavy chain gene
      and germline configurations of T-cell receptor gene and c-myc 3rd exon gene. The
      immunophenotype and genotype of this neoplasm were different from those of
      previously reported BLs, but identical to those of B-cell lymphoblastic lymphoma.
      This case, therefore, was regarded as B-cell type lymphoblastic lymphoma
      containing lipid droplets.

PMID- 7642167
TI  - The role of the hippocampus in the pathogenesis of psychiatric disorders.

PMID- 7642168
TI  - Recent aspect of the role of peripheral dopamine and its receptors in the
      pathogenesis of hypertension.
AB  - Dopamine is an essential and indispensable catecholamine, which acts not only as
      a neurotransmitter in dopaminergic and noradrenergic sympathetic neurons but also
      as an autocrine/paracrine substance in non-neuronal tissues. The regulatory
      mechanism of dopamine synthesis in neuronal tissues seems to be different from
      that in non-neuronal tissues. Among receptors specifically bound to dopamine,
      five different receptors have already been cloned. Dopamine exhibits vasodilative
      and natriuretic effects by stimulating specific dopamine receptors located in
      renal tubular cells, blood vessels, etc. Physiological effects of dopamine appear
      to be protective against hypertension and sodium retention. Spontaneously
      hypertensive rats (SHR) are known to have an enhanced dopamine generation
      associated with the increased sympathetic nervous activity. A defect of renal D1
      receptor-mediated coupling to adenylate cyclase has also been demonstrated in
      SHR. On the other hand, it has been reported that Dahl salt sensitive rats
      exhibit defective dopamine synthesis during high salt intake, which may be a
      definitive abnormality in this strain. The pathophysiological role of peripheral
      dopamine is essential hypertensive patients is still controversial. Considering
      the previous studies, it seems to be the case that essential hypertensive
      patients with increased sympathoadrenergic activity show enhanced dopaminergic
      discharge where dopamine may negatively modulate high blood pressure, and that
      stable essential hypertensive patients with salt-sensitivity and/or suppressed
      renin activity show insufficient dopamine synthesis in the kidney.

PMID- 7642169
TI  - Histogenesis and pathogenesis of follicular small cleaved cell lymphoma (FSCCL),
      diffuse small cleaved cell lymphoma (DSCCL) and intermediate lymphocytic
      lymphoma/lymphocytic lymphoma of intermediate differentiation (ILL/IDL).
AB  - We have investigated the cellular origin and/or pathogenesis of follicular small
      cleaved cell lymphoma (FSCCL), diffuse small cleaved cell lymphoma (DSCCL) and
      intermediate lymphocytic lymphoma/lymphocytic lymphoma of intermediate
      differentiation (ILL/IDL) based on a series of immunologic and molecular genetic
      (bcl-1, bcl-2 and bcl-3 genes) studies. These studies have led to the conclusion
      that the cellular origin or pathogenesis of ILL/IDL and DSCCL is distinctly
      different from that of FSCCL: (1) FSCCL is a neoplastic counterpart of follicular
      center cells (FCC) of secondary follicles because of the presence of CD10 and bcl
      2 gene rearrangement and the absence of CD5 and bcl-1 gene rearrangement; (2)
      DSCCL and ILL/IDL are a neoplastic counterpart of mantle zone (MZ) B lymphocytes
      because of the presence of CD5 and bcl-1 gene rearrangement and absence of CD10
      and bcl-2 gene rearrangement; and (3) FSCCL scarcely develops into DSCCL, and the
      previously proposed concept that DSCCL represents a diffuse counterpart of FSCCL
      does not hold good. These results indicate that DSCCL and ILL/IDL are identical,
      derived from primary follicular cells or MZB cells of secondary follicles, and
      should be unified under MZB lymphocyte-derived lymphomas. They are distinguished
      from FCC-derived lymphomas in morphologic, immunologic, cytogenetic and molecular
      genetic features. Bcl-1 and bcl-2 genes may be associated with the pathogenesis
      of FCC-derived lymphoma and MZB lymphocyte-derived lymphoma, respectively.

PMID- 7642170
TI  - In vitro growth of neonatal rat islet cells is stimulated by adhesion to matrix.
AB  - We examined DNA synthesis in non-enzymatically isolated neonatal rat pancreatic
      islets sub-cultured to eliminate fibroblast contamination, which was excluded
      both by demonstrating no effect of fibroblast growth factor (FGF) on 3H-thymidine
      incorporation and by immunofluorescence of attached islets using a mouse anti
      fibroblast monoclonal antibody. 3H-thymidine incorporation in islets increased
      with increasing glucose up to a concentration of 21.1 mM in both free-floating
      islets (11,789 cpm/micrograms DNA +/- 1,610 SEM) and islets attached to
      fibronectin coated plastic (43,043 cpm/micrograms DNA +/- 9,203 SEM). These
      values were significantly higher when compared to 3H-thymidine incorporation in
      medium containing 11.1 mM glucose (p < 0.007, and p < 0.0001 for free-floating
      and attached islets respectively). 3H-thymidine incorporation was significantly
      higher in attached islets than in free-floating islets at all glucose
      concentrations tested (p < 0.005 at 11.1 mM, 16.1 mM, and 21.1 mM; and p < 0.01
      at 26.1 mM). 5-bromo-2'-deoxyuridine (BrDU) staining of islets showed an
      increased number of positive nuclei in cells localised within attached islets
      (37.6 nuclei per islet +/- 5.1 SEM) compared to free-floating islets (7.62 nuclei
      per islet +/- 1.04 SEM, p < 0.001), indicating that attachment influenced
      proliferation of islet cells not physically in contact with the matrix. No
      difference in glucose-stimulated insulin release was observed between attached
      and free-floating islets. In conclusion, a fibroblast free islet culture was used
      to document the stimulatory effect of islet attachment on DNA synthesis, which
      was greater than the stimulation exerted by glucose alone.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7642171
TI  - Protective effect of gamma-hydroxybutyrate and nicotinamide on low-dose
      streptozotocin-induced diabetes in mice.
AB  - The purpose of this study was to investigate the effect of a treatment by gamma
      hydroxybutyrate (GHB) and nicotinamide (NA) on low-dose streptozotocin (STZ)
      induced diabetes in mice. Mean plasma glucose level was significantly elevated in
      mice given STZ by day 12 after the first STZ injection compared to controls (15.0
      +/- 4.7 vs 8.0 +/- 1.6 mmol/l, p < 0.001) and 100% of the animals were severely
      diabetic by day 18. Plasma glucose levels remained in the normal range and no
      diabetic values were found in mice treated with combined treatment by GHB and NA
      for 25 days. However, hyperglycemia and glycosuria appeared within one week after
      discontinuation of the treatment. Treatment by either GHB or NA alone had only a
      slight and transient effect in preventing hyperglycemia. In vitro experiment on
      isolated pancreatic islets demonstrated that STZ-induced loss of insulin response
      to glucose was also counteracted by incubation with GHB and NA (Peak insulin
      response to 16.4 mM glucose: 0.69 +/- 0.31 vs 3.03 +/- 0.67 microU/islet/min),
      but not by GHB or NA alone. These results indicate that GHB and NA have
      complementary effects in preventing STZ-induced beta cell damage both in vivo and
      in vitro. This should be taken into account for future preventive strategies in
      human insulin-dependent diabetes mellitus.

PMID- 7642172
TI  - Triiodothyronine decreases gammaglutamyltranspeptidase expression in cultured rat
      hepatocytes.
AB  - Recently, an increase in gammaglutamyltranspeptidase (GGT) activity and mRNA in
      liver of hypothyroid rats has been reported. The aim of this study was to verify
      if triiodothyronine (T3) can directly affect GGT expression in primary cultures
      of rat hepatocytes. Results obtained from adult rat hepatocytes cultured in serum
      free medium demonstrate: 1) a rise in GGT mRNA level magnified by dexamethasone
      during the maintenance of hepatocytes in culture which parallels the stimulation
      of GGT activity; 2) a negative effect of T3 on GGT activity of cultured
      hepatocytes which reflects a specific inhibition of GGT gene expression. The T3
      effect on GGT expression in cultured hepatocytes is in line with previous
      observations on hypothyroid rat liver suggesting an important role for thyroid
      hormone in maintaining the differentiated adult liver phenotype in the rat.

PMID- 7642173
TI  - Long-term effect of octreotide in acromegaly on insulin resistance.
AB  - An important feature of acromegaly is a reduced action of insulin on hepatic
      gluconeogenesis and peripheral glucosal disposal. Octreotide (SMS) exerts complex
      effects on hormonal and metabolic regulations affecting glucose homeostasis.
      Eight patients with active acromegaly despite surgical intervention (age 44.8 +/-
      3.5 years, BMI 27.3 +/- 1.6 kg/m2, lean body mass (LBM) 70 +/- 3.2%, blood
      glucose 5.24 +/- 0.26 mmol/l, HbA1c < or = 6.5%) were investigated before and
      after 6 months of treatment with SMS in an open trial. SMS was injected sc. at a
      dosage between 100-200 micrograms t.i.d. Mean GH and IGF1 levels during SMS
      therapy were significantly reduced (GH 9.6 +/- 1.9 ng/ml vs. 4.9 +/- 1.3 ng/ml, p
      < 0.05; IGF1 729.5 +/- 84 ng/ml vs. 415 +/- 49 ng/ml, p < 0.05). OGTT and
      euglycaemic-clamp-studies were performed before and after 6 months of SMS
      treatment. The glucosal disposal rate on average (insulin infusion rate 40
      mU/m2/min) was not significantly changed following SMS treatment (McLBM before
      3.60 +/- 0.38, after 3.95 +/- 0.41 mg/kg LBM/min). There was a positive
      correlation (r = 0.620) between the individual change of IGF1 and the change of
      McLBM. Additionally there was no significant difference of serum basal insulin
      levels (0.19 +/- 0.01 vs. 0.23 +/- 0.06 nmol/l) as well as basal C-peptide levels
      (0.79 +/- 0.07 vs. 0.47 +/- 0.04 nmol/l) before and with SMS treatment. We
      therefore conclude that long-term treatment of acromegalic patients with SMS,
      which achieves a successful reduction of GH and IGF1 levels, does not always
      guarantee a significant improvement in glucose metabolism.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7642174
TI  - Decreased expression of the GLUT4 glucose transporter protein in adipose tissue
      during pregnancy.
AB  - Insulin resistance involves impaired activities of the glucose transport system
      in insulin target tissues. We therefore investigated the GLUT4 glucose
      transporter protein in adipose tissues from the pregnant women with normal
      glucose tolerance and from women with gestational diabetes mellitus, and compared
      these to nonpregnant women. Three groups of women were studied: nonpregnant women
      with normal glucose tolerance (N = 6), pregnant women with normal glucose
      tolerance (N = 6, gestational week 38.0 +/- 0.3), and pregnant women with
      gestational diabetes mellitus (N = 3, gestational week 38.6 +/- 0.3). The
      abdominal subcutaneous adipose tissues obtained from each group were subjected to
      analysis of the GLUT4 glucose transporter protein. The presence of the GLUT4
      glucose transporter protein in the three groups was quantitatively determined by
      Western blot analysis of detergent-soluble adipose tissue extracts using anti
      GLUT4 antibody. GLUT4 glucose transporter protein concentration in the adipose
      tissue of pregnant women were significantly lower than that in nonpregnant women,
      and this difference was more profound in women with gestational diabetes
      mellitus. We demonstrated that the content of GLUT4 protein was decreased in
      adipose tissue from normal pregnancy compared to nonpregnant women.

PMID- 7642175
TI  - Insulin, but not estrogen, correlated with indexes of desaturase function in
      obese women.
AB  - This study determined the associations of serum insulin and estrogen with fatty
      acid composition, fatty acid product/substrate ratios used as indexes of
      desaturase enzyme function, and platelet aggregation in obese and lean women.
      Thirty women were classified as obese (n = 8) or lean (n = 21) based on body mass
      index. Obese women were characterized by higher insulin levels (p < 0.05) but
      fasting glucose levels did not differ (p > 0.05) from lean women. Insulin
      positively correlated with increased C20:4n6/C18:3n6 (index of delta 5
      desaturase) (p < 0.05) and C20:4n6/C18:2n6 (index of overall n6 pathway activity)
      (p < 0.01) in serum, and the n5 pathway in platelets (p < 0.01), but there was no
      correlation for insulin with platelet C18:3n6/C18:2n6 (index of delta 6
      desaturase activity). Insulin was also positively related (p < 0.01) to
      aggregation as measured by impedance and negatively related to lag time (p <
      0.05). Platelets of obese women aggregated more (p < 0.05) compared to lean women
      and began aggregating faster (p < 0.05), suggesting the possibility that the
      obese women were at greater risk for enhanced blood clotting. Plasma estrogen was
      correlated with age (p < 0.05) but not for other variables studied (p > 0.05).
      Insulin, but not estrogen, appears to influence desaturase activity, as
      demonstrated by increased desaturase function associated with hyperinsulinemia in
      obese women.

PMID- 7642176
TI  - Long-term effects of simvastatin in hypercholesterolemic patients with NIDDM and
      additional atherosclerotic risk factors. Hyogo Simvastatin Study Group.
AB  - Effects of 12 months of simvastatin treatment were examined in 48 NIDDM patients
      with total serum cholesterol levels exceeding 220 mg/dl and were compared with
      those in 35 nondiabetic patients with hypercholesterolemia. In the diabetic
      group, 5-10 mg of simvastatin given once daily at bedtime significantly lowered
      total cholesterol (21%). LDL cholesterol (28%), apoB (15%) and triglycerides (8%)
      levels. These changes were identical to those in the nondiabetic group, except
      for triglycerides which did not change significantly. HDL cholesterol increased
      significantly in the nondiabetic group but not in the diabetic group. The
      reductions in LDL cholesterol and apoB in hypercholesterolemic patients with
      NIDDM were not influenced by gender, age, glycemic control, the presence or
      absence of systemic hypertension, obesity and overt proteinuria. In addition, the
      decrease in LDL cholesterol was not affected by the number of risk factors per
      patient. Simvastatin did not significantly alter hemoglobin A1c or fasting plasma
      glucose and was well tolerated in both groups. Simvastatin produced beneficial
      effects on serum lipids and apolipoproteins and neutral effects on glycemic
      control in hypercholesterolemic patients with NIDDM, whether or not they had an
      additional atherosclerotic risk factor.

PMID- 7642177
TI  - Parathyroid hormone secretion and serum calcium concentration--a deterministic
      view of its regulation.
AB  - In seven normal men we investigated the basal secretion of PTH by blood sampling
      in 30 sec intervals for estimation of intact PTH and at 2-min intervals for
      measurement of ionized calcium. In 4 of these subjects we also investigated the
      PTH-secretion under conditions of intermittent hypercalcemia and hypocalcemia.
      Our measurements demonstrate the existence of three time scales in the secretion
      of PTH, viz. short-term pulses (faster than 2 min), an intermediate pattern of
      adjusting PTH levels to changed Ca2+ averages, and finally a long-term coupling
      between PTH and Ca2+ averages after 20 min. Ionized calcium controls the long
      term regulation and intermediate adaptation mechanisms, but the short-term
      fluctuations seem to be due to spontaneous secretion.

PMID- 7642178
TI  - In vivo stimulation of insulin secretion by novel esters of succinic acid.

PMID- 7642179
TI  - The effect of GTP gamma S on insulin binding to human liver plasma membranes.

PMID- 7642180
TI  - Hypothetical relationship between the presence of TNF alpha in the sera of
      insulin-dependent diabetes mellitus type I patients and control of the disease.

PMID- 7642181
TI  - Relationships among B-endorphin (B-EP), insulin and atrial natriuretic peptide
      (ANP) in patients with simple obesity.

PMID- 7642182
TI  - Social and cognitive processes in interpersonal communication: implications for
      advanced telecommunications technologies.
AB  - Interactive multimedia conferencing systems, in which two or more remotely
      located people can work on cooperative tasks through shared audio, video, and
      data, appear to be the wave of the future. However, because of great advances in
      the underlying technology of multimedia conferencing systems, many design
      decisions have been driven by what is technically feasible as opposed to what
      will best suit the needs of the users. In this paper we provide a framework for
      the design and evaluation of features in advanced telecommunications products and
      services which is derived from empirical research on interpersonal communication.
      We also discuss implications of this research for the development and use of
      advanced telecommunications technologies.

PMID- 7642183
TI  - Telepresence in videocommunications: a study on stereoscopy and individual eye
      contact.
AB  - We conducted two experiments to investigate how stereoscopy and technologies that
      allow individual eye contact affect the impression of telepresence in video
      conferencing. Telepresence is defined as the degree to which participants of a
      telemeeting get the impression of sharing space with the remote site. Results
      revealed, among other things, that stereoscopy increases telepresence and makes
      videoconferencing more attractive. In addition, we found that reduced eye contact
      angles enhance the recognizability of individually addressed nonverbal signals.
      However, a setup that eliminates horizontal and vertical eye contact angles seems
      to be advantageous only in conferences with more than two persons per site.

PMID- 7642184
TI  - Effects of a laser-induced temporary scotoma on target acquisition performance.
AB  - Lasers commonly used in industry and the military are increasingly being
      recognized as possible hazards to vision and visually guided tasks. This study
      examined the effects of laser-induced visual loss on target acquisition
      performance. An argon laser was used to produce a temporary central scotoma.
      Observers searched for variable-contrast aircraft that were embedded in
      backgrounds of differing complexity. The laser exposures increased acquisition
      times 2 to 12 times over baseline levels, indicating that the degree of visual
      deficit was task dependent. Acquisition time increased as background complexity
      increased and target contrast decreased. However, target motion facilitated
      acquisition performance and mitigated the laser effect. Although contrast had a
      systematic effect on acquisition performance, it was clear that factors other
      than contrast contributed to target visibility. Other factors that may have
      affected visibility included distractors and masking effects introduced by the
      structured backgrounds.

PMID- 7642185
TI  - Self-selected manual lifting technique: functional consequences of the interjoint
      coordination.
AB  - The pattern of movement self-selected by 39 subjects to lift light loads from 9
      cm above the ground is described in kinematic and electromyographic terms.
      Hamstring length changes were estimated from hip and knee angular kinematics.
      Subjects adopted a posture at the start of the lift intermediate between stoop
      and full-squat postures. A consistent coordination between knee, hip, and lumbar
      vertebral joints during lifting was described through calculation of the relative
      phase between adjacent joints and found to be exaggerated with increases in load
      mass. During the early phase of lifting, knee extension leads hip extension,
      which in turn leads extension of the lumbar vertebral joints. Early in the
      lifting movement, when load acceleration is greatest, the erectores spinae are
      thus relatively long and shortening slowly. Both of these factors produce greater
      back extensor strength. Rapid hamstring shortening is also delayed, which
      enhances their strength, and coactivation of the monoarticular knee extensors and
      biarticular hamstring observed early in the lifting movement suggested that the
      knee extensors contribute to hip extension through a tendinous action of the
      hamstrings.

PMID- 7642186
TI  - Relative effects of age and compromised vision on driving performance.
AB  - The aim of this study was to determine the relative effects of age and
      compromised vision on driving-related skills and on-road accidents. A total of
      107 subjects were tested. They represented four groups that varied in age and
      visual status, as follows: (1) a younger, normally sighted group; (2) an older,
      normally sighted group; (3) a younger, visually compromised group; and (4) an
      older, visually compromised group. Driving performance was assessed by self
      reported and state-recorded accident frequency and by an evaluation of
      performance on an interactive driving simulator. The older groups had poorer
      driving-related skills, as measured with our interactive driving simulator, than
      had the younger groups, but they did not have significantly higher on-road
      accident rates than the younger groups. The older subjects and those with
      compromised vision had reduced risk-taking scores, as measured with a self-report
      questionnaire. In addition, all older drivers had increased eye movements and had
      slower simulator driving speeds, which suggests that behavioral compensation is
      made for visuocognitive/motor deficits. Regression analyses showed that
      compromised vision and visual field loss predicted real-world accidents in our
      study population.

PMID- 7642187
TI  - Force-sensing microprobe for precise stimulation of mechanosensitive tissues.
AB  - Quantitative study of the transduction mechanisms in mechanically sensitive nerve
      terminals has been impeded by the lack of instrumentation with which to generate
      precisely controlled, physically localized mechanical stimuli. We have developed
      high-resolution force sensing mechanical microprobes for use in the
      characterization of such nerve terminals. This paper describes their design,
      fabrication, and testing. A microprobe is comprised of a 0.5- to 2-mm long
      silicon cantilever beam projecting from a larger supporting silicon substrate.
      Acting as the variable leg of a Wheatstone bridge circuit, a piezoresistive
      polysilicon element located at the base of the beam is used to measure the
      stimulation force applied at the tip. The microprobes exhibit a stable, linear
      relationship between the stimulation force and the resulting output voltage
      signal. Stimulation forces up to 3 mN have been generated with a measurement
      resolution of 10 microN. These microprobes have been used as the force sensing
      element of a closed loop feedback-controlled stimulation system capable of
      stimulating the mechanoreceptive nerve terminals of the rabbit corneal
      epithelium.

PMID- 7642188
TI  - A silicon micromachined device for use in blood cell deformability studies.
AB  - An application of silicon micromachining to the analysis of blood cell rheology
      is described. The system, based upon a micromachined flow cell, provides a
      specific measurement of each cell in a statistically significant population in
      terms of both flow velocity profile and an index of cell volume while the cells
      flow through an array of microchannels. The rationale, design, and fabrication of
      the silicon micromachined flow cell is discussed. Interrelated considerations
      determining the design of the associated fluidic, mechanical, imaging, and real
      time image analysis subsystems are examined. Sample data comparing normal and
      iron deficiency anaemic blood are presented to illustrate the potential of this
      technique.

PMID- 7642189
TI  - Dynamic extraction of visual evoked potentials through spatial analysis and
      dipole localization.
AB  - The dynamic extraction of evoked potential is a problem of great interest in EEG
      signal processing. In this paper, a comprehensive method is presented which
      integrates spatial analysis and dipole localization to make full use of the
      spatial-temporal information contained in the multichannel stimulation records. A
      realistic double boundary head model is constructed through CT scans and a two
      step method devised to overcome the ill-posed nature of the forward problem of
      EEG caused by the low conductivity of the skull. As a result, visual evoked
      potentials can be effectively extracted from only two consecutive records and the
      dynamic information of visual evoked potential thus procured. The efficiency of
      the presented method has been verified by means of computer simulation and a
      clinical experiment.

PMID- 7642190
TI  - Estimation of shape characteristics of surface muscle signal spectra from time
      domain data.
AB  - Myoelectric manifestations of muscle fatigue have been described by monitoring
      the first-order moment (mean frequency) of the power spectral density function
      during voluntary or electrically elicited sustained contractions. Higher order
      central moments provide additional information about the width, skewness, and
      kurtosis of the spectrum and its shape changes, thereby providing a description
      of slow nonstationarities more accurate than that allowed by the mean frequency
      alone. In 1986, B. Saltzberg introduced a method of representing the moments of
      the power spectral density function of band limited signals, without computing
      the Fourier transform, as weighted sums of samples of the autocorrelation
      function. If we allow for oversampling of the signal (and therefore of its
      autocorrelation function), more efficient weighted sums can be found which give
      Saltzberg's formula as a limiting case. The faster rate of decay of the weights
      implies a faster convergence of the estimates and the need to compute fewer
      samples of the autocorrelation function. The algorithm is particularly suitable
      for: 1) analysis of evoked potentials (M-waves), because it does not need zero
      padding to increase resolution and operates on any number of samples, and 2) on
      line implementation by dedicated microprocessors performing simultaneous spectral
      moment analysis on a number of parallel channels.

PMID- 7642191
TI  - The application of cepstral coefficients and maximum likelihood method in EMG
      pattern recognition.
AB  - A new technique for classifying patterns of movement via electromyographic (EMG)
      signals is presented. Two methods (conventional autoregressive (AR) coefficients
      and cepstral coefficients) for extracting features from EMG signals and three
      classification algorithms (Euclidean Distance Measure (EDM), Weighted Distance
      Measure (WDM), and Maximum Likelihood Method (MLM)) for discriminating signals
      representative of broad classes of movements are described and compared. These
      three classifiers are derived from Bayes classifier with some assumptions, the
      relationship among them is discussed. The conventional MLM is modified to avoid
      heavy matrix inversion. Six able-bodied subjects with two pairs of surface
      electrodes located on bilateral sternocleidomastoid and upper trapezius muscles
      were studied in the experiment. The EMG signals of 20 repetitions of 10 motions
      were analyzed for each subject. Experimental results showed that mean recognition
      rate of the cepstral coefficients was at least 5% superior to that of the AR
      coefficients. The improvement achieved by the cepstral method was statistically
      significant for all the three classifiers. Reasons for the superiority of
      cepstral features were investigated from the feature space and frequency domain,
      respectively. The cepstral coefficients owned better cluster separability in
      feature space and they emphasized the more informative part in the frequency
      domain. The discrimination rate of the MLM was the highest among three
      classifiers. Incorporation of the cepstral features with the MLM could reduce the
      misclassification rate by 10.6% when compared with the combination of AR
      coefficients and EDM. Proper choice of five of ten motions could further raise
      the recognition rate to more than 95%.

PMID- 7642192
TI  - Fuzzy classification of patient state with application to electrodiagnosis of
      peripheral polyneuropathy.
AB  - A methodology which accounts for uncertainty or imprecision in experimental
      observations and both norm and pathology definitions is developed on the basis of
      a distance measure between fuzzy numbers. These fuzzy numbers may represent,
      respectively, the measurements, norm, and pathology. The distance measure, called
      normalized fuzzy pathology index (NFPI), evaluates the difference of distance
      between observed experimental values for a given patient and norm on the one
      hand, and pathology on the other hand. The NFPI characterizes patient state as a
      continuous index; however, to conform to medical usage, categories of values are
      defined. Each of these categories corresponds to a linguistic variable. The case
      study used to illustrate the methodology is the electrodiagnosis of peripheral
      polyneuropathy in diabetic patients. Here, four initial linguistic categories are
      defined by a physician, namely: normal state, borderline state, clear-cut, and
      severe pathology. The NFPI is calculated in three cases that provide a
      sensitivity analysis on measurement fuzziness and distance function weighting.
      The model is calibrated using 203 cases and validated using 291 different cases.
      The results correspond very closely to the physician's diagnosis. The loss of
      information in discretizing the continuous state of patients is discussed.
      Transferring this fuzzy approach to other cases where the concept of distance is
      relevant offers no difficulty.

PMID- 7642193
TI  - Functional design features and initial performance characteristics of a magnetic
      implant guidance system for stereotactic neurosurgery.
AB  - A helmet with a roughly cubic array of six super-conducting coils is used to
      apply force on a small permanent magnet pellet in brain or in brain phantom
      material. This apparatus, called the Magnetic Stereotaxis System, will be used to
      deliver drugs and other therapies directly into deep brain tissues, under control
      of a computer and fluoroscopic imaging system. This paper considers only the
      force application aspects of the instrument. The primary design features of the
      helmet and power supply controls are presented, along with field plot data and
      single-axis motion results. The field plot data show that agreement with the
      finite-element iron-free field calculations is sufficiently high (> 1%) for the
      instrument. These preliminary motion data indicate accuracy better than 2 mm for
      the impulsive pellet motion, even though the visual position observations had
      significantly greater error than the completed imaging system will have. The
      companion paper will take up analysis of the control aspects of the motion, and
      our recent solutions to difficulties found in the experimental work described
      here.

PMID- 7642194
TI  - Characteristics of an improved magnetic-implant guidance system.
AB  - The previous companion paper described the motivation, design, and early
      experiments of a Magnetic Stereotaxis System. The part of the system considered
      in these papers is a helmet with a roughly cubic array of six superconducting
      coils used to apply force on small permanent magnet pellets in brain and in brain
      phantom material. This apparatus will be used to deliver drugs and other
      therapies directly into deep brain tissues, under control of a computer and
      fluoroscopic imaging system. Here, we analyze the general stability problems of
      controlling the currents in the coils for impulsive stepwise motion of the
      pellet, subject to quench avoidance in the superconducting coils, and in the face
      of Earnshaw's theorem governing stability in static magnetic fields. We also
      describe solutions that have been found to the primary difficulties limiting
      controlled pellet motion in the studies presented in the companion paper.

PMID- 7642195
TI  - Reducing muscle fatigue in FES applications by stimulating with N-let pulse
      trains.
AB  - Applications of electrical stimulation for restoration of functional movements
      such as standing, gait, and grasp have always been hindered by the rapid fatigue
      of stimulated muscle. This paper describes an experimental investigation of
      stimulation with N-lets (a set of N closely spaced stimulation pulses) as a means
      of producing contractions with improved fatigue characteristics. Experiments were
      conducted on 27 able-bodied and four SCI human subjects using surface stimulation
      of the quadriceps muscle to produce isometric knee joint torque. Based upon
      evidence from the literature on muscle fatigue, parameters of the N-let trains
      for N = 1-6 were optimized to produce the most force per pulse. The results
      demonstrated that: 1) nonlinear summation of the twitch response occurs in human
      subjects with N-let surface stimulation; 2) for most subjects, doublet
      stimulation (N = 2) with a pulse interval of about 5 ms produced the maximum
      torque-time integral per pulse of the resulting twitch; and 3) on average,
      optimal N-let stimulation resulted in a 36% increase in isometric torque tracking
      when compared to traditional singlet stimulation. The results have immediate
      implications for alleviating the problem of premature fatigue during functional
      electrical stimulation.

PMID- 7642196
TI  - Multipoint temperature control during hyperthermia treatments: theory and
      simulation.
AB  - A real-time multipoint feedback temperature control system has been designed and
      implemented with an ultrasound phased-array applicator for hyperthermia. The
      control parameters are the total power available from the supply and the dwell
      times at a sequence of preselected heating patterns. Thermocouple measurements
      are assumed for temperature feedback. The spatial operator linking available
      heating patterns to temperature measurements is measured at the outset of the
      treatment and can be remeasured on line an adaptive implementation. A significant
      advantage of this approach is that the controller does not require a priori
      knowledge of either the placement of the thermocouples or the power distribution
      of the ultrasound heating patterns. Furthermore, the control loop uses a
      proportional integral (PI) gain in conjunction with a singular value
      decomposition (SVD) of the spatial transfer operator. This approach is
      advantageous for robust implementation and is shown to properly balance the power
      applied to the individual patterns. The controller also deals with saturation in
      the inputs without integrator windup and, therefore, without temperature
      overshoot. In this paper, we present the theoretical formulation and
      representative simulation results of the proposed controller. The control
      algorithm has been verified experimentally, both in vitro and in vivo. A
      subsequent paper describing these results and the practical implementation of the
      controller will follow.

PMID- 7642197
TI  - Noninvasive estimation of tissue temperature response to heating fields using
      diagnostic ultrasound.
AB  - A noninvasive technique for monitoring tissue temperature changes due to heating
      fields using diagnostic ultrasound is described in this paper. The approach is
      based on the discrete scattering model used in the tissue characterization
      literature and the observation that most biological tissues are semi-regular
      scattering lattices. It has been demonstrated by many researchers and verified by
      us that the spectrum of the backscattered radio frequency (RF) signal collected
      with a diagnostic ultrasound transducer from a semi-regular tissue sample
      exhibits harmonically related resonances at frequencies determined by the average
      spacing between scatterers along a segment of the A-line. It is shown
      theoretically and demonstrated experimentally (for phantom, in vitro, and in vivo
      media) that these resonances change with changes in the tissue temperature within
      the processing window. In fact, changes in the resonances (delta f) are linearly
      proportional to changes in the temperature (delta T), with the proportionality
      constant being determined by changes in the speed of sound with temperature and
      the linear coefficient of thermal expansion of the tissue. Autoregressive (AR)
      model-based methods aid in the estimation of delta f. It should be emphasized
      that this new technique is not a time of flight velocimetric one, so it
      represents a departure from previously used ultrasonic methods for tissue
      temperature estimation.

PMID- 7642198
TI  - A simple method to incorporate the effects of an RF shield into RF resonator
      analysis for MRI applications.
AB  - A simple but effective method is proposed to incorporate the effects of a radio
      frequency (RF) shield into the analysis of RF resonators for magnetic resonance
      imaging (MRI) applications. It is shown that the method can predict the resonant
      frequencies of RF resonators within 5% of the measured values.

PMID- 7642199
TI  - Modeling of micturition characteristics based on prostatic stiffness modulation
      induced using hormones and adrenergic antagonists.
AB  - We present a biosensor intended to evaluate prostatic stiffness. The stiffness of
      the prostate was modulated using hormonal induction and adrenergic stimulation.
      The results show that the sensor can be sufficiently accurate to discriminate
      between soft prostates used as controls and those stiffened with hormones. The
      modulation produced by an adrenergic agent on prostatic stiffness was detected
      using this system. An electrical model was constructed embodying the parameters
      of prostatic stiffness, micturition frequency, and volume, demonstrating that
      prostatic stiffness correlates with micturition frequency.

PMID- 7642200
TI  - Hypoglycemic action of Murraya koenigii (curry leaf) and Brassica juncea
      (mustard): mechanism of action.
AB  - Effect of Murraya koenigii and Brassica juncea on carbohydrate metabolism has
      been studied using rats as experimental animals. Both showed significant
      hypoglycemic action. There was increase in the concentration of hepatic glycogen
      and glycogenesis, as evident from the increased activity of glycogen synthetase,
      and decrease in glycogenolysis and gluconeogenesis as evident from the decreased
      activity of glycogen phosphorylase and gluconeogenic enzymes.

PMID- 7642201
TI  - Myoinositol and peroxidation--an in vitro study on human cataractous lens and
      human erythrocytes.
AB  - The effect of myoinositol on in vitro peroxidation induced by hydrogen peroxide
      in human erythrocytes and human cataractous lenses has been investigated. The
      lipid peroxidation was monitored as levels of thio barbituric reacting substances
      (TBARS). Addition of myoinositol decreased the peroxidation effect of hydrogen
      peroxide in a dose dependent manner. The results suggest a new antioxidant
      property for inositol.

PMID- 7642202
TI  - Photophysical and photobiological properties of 3-carbethoxypsoralen.
AB  - 3-Carbethoxypsoralen (3-CP), a linear tricyclic psoralen, known for its
      photoreaction with DNA to form monofunctional cyclobutane adducts with pyrimidine
      bases, was found to produce a highly reactive cytotoxic species, singlet oxygen
      (1O2) to a greater extent than several other linear psoralens such as psoralen, 8
      MOP, 5-MOP or angular psoralens (angelicin). 3-CP also produced superoxide
      radicals (O2-.) at a rate slower than psoralens in the following order:psoralen >
      angelicin > 3-CP > 8-MOP > 5-MOP. 1O2 produced by photoactivated 3-CP was found
      to oxidize tyrosine and Dopa to Dopachrome, and subsequently their conversion to
      melanin. It also induced photooxidation of 2'-deoxyguanosine. Reactive oxygen
      species produced by 3-CP also induced lipid peroxidation. The rate of dopachrome
      formation to promote its conversion to melanin and lipid peroxidation by 3-CP and
      other linear and angular psoralens and hematoporphyrin derivatives may be related
      to their skin photosensitizing ability and the rate of 1O2 production. Topically
      applied 3-CP on hairless mice exposed to UVA radiation was found to be a
      nonphotocarcinogenic agent in contrast to 8-MOP, which under similar conditions
      produced a 70% tumour yield (squamous cell carcinoma) in 65 weeks. 3-CP was
      observed to be a photolabile compound and was converted to a dihydro-form as
      previously reported by other investigators. The photoconversion of 3-CP to 4',5'
      dihydro-3-CP was enhanced under N2, whereas, under O2 atmosphere, lesser degree
      of photoconversion was observed, thus, indicating that reduction takes place via
      an anoxic or Type I mechanism. The significance of these observations are
      discussed in relation to the skin photosensitizing, nonphotocarcinogenic, and
      photochemotherapeutic potential of 3-CP.

PMID- 7642203
TI  - 1H NMR investigation of the interaction of berberine and sanguinarine with DNA.
AB  - Interaction of the alkaloids, berberine and sanguinarine with calf thymus DNA has
      been studied by 1H NMR. All proton resonances of the two compounds have been
      assigned using 2D-COSY, NOESY and ROESY spectra. Berberine has been found to
      partially intercalate into DNA, while sanguinarine shows normal intercalation and
      also binds more firmly to DNA. The NMR experiments indicate that sanguinarine is
      more potent than berberine in its activity.

PMID- 7642204
TI  - Newly synthesised mRNA as a probe for identification of wound responsive genes
      from potatoes.
AB  - A method for the selective isolation of wound induced RNA from potato tuber has
      been standardised by labeling with 4-thiouridine and subsequent affinity
      chromatography on Affigel 501 phenyl-mercury Sepharose column. About 30% of the
      total RNA isolated from wounded potato tissue was found to be synthesized de
      novo. The relative abundance of wound induced RNAs was confirmed by using two
      well identified wound inducible gene probes of hydroxyproline-rich glycoproteins
      (HRGP) and proteinase inhibitor I. The selectively separated wound induced mRNA
      was used to make cDNA probes. By screening a--gt10 cDNA library from wounded
      potato tissue with these cDNA probes, several wound responsive genes were
      identified. Wound inducible expression of these genes was further confirmed by
      Northern hybridization and their tissue specific expressions were examined. Thus,
      a simple method for the direct identification of wound responsive genes from
      potato was developed.

PMID- 7642205
TI  - Ontogeny, glycosylation and modulation by dialysis, sodium and nucleotides of the
      rat brain delta opioid receptor studied with anti-idiotypic antibodies to anti
      leucine enkephalin.
AB  - Ontogeny of the rat brain delta opioid receptor in 1-60 days old animals has been
      studied with anti-idiotypic antibodies to anti-leucine enkephalin. It is found
      that delta opioid receptors are present in rats from birth and attain adult
      levels by 28 days and these receptors are glycosylated and inhibited by Na+, GTP,
      ATP and CTP at all ages. Adult membrane-bound and solubilized delta opioid
      receptors are inhibited to similar extents by Na+ (100 mM), GTP, ATP and CTP (50
      microM). Dialysis of the adult membrane-bound receptor led to 81% loss in binding
      which was restored by 100 mM Na+, 50 microM GTP, ATP and CTP to 77, 72, 87 and
      94% respectively and by 100 mM NH4+, Mg2+, Ca2+ and Mn2+ to 63, 43, 57 and 73%
      respectively. Dialysis of the solubilized receptor resulted in 23% loss in
      binding with Na+ (100 mM), GTP and ATP (50 microM) inhibiting receptor binding to
      46, 62 and 54% respectively, while CTP (50 microM) restored binding to 88%. These
      studies indicate that the delta opioid receptor can be probed with anti-idiotypic
      antibodies to anti-leucine enkephalin, that functional, glycosylated receptors
      are present at birth in rats and that the adult membrane-bound and solubilized
      receptors are modulated differently by dialysis.

PMID- 7642206
TI  - Lipid peroxidation of colonocyte membranes.
AB  - Effects of various oxidants on the colonic membrane lipid peroxidation have been
      studied in rats. 2,2-Azobis (2-amidinopropane) dihydrochloride (ABAP), which
      generates free radicals by thermal decomposition, induced peroxidation as judged
      by the formation of conjugated diene, malondialdehyde (MDA), and depletion of
      arachidonic acid. Exposure to other oxidants which require free iron for
      peroxidation was ineffective. Alpha tocopherol level was not altered on exposure
      to various oxidants except with ABAP which depleted its level in these membranes.
      Exposure of the membranes to both ABAP and xanthine-xanthine oxidase (X-XO)
      decreased total protein thiols, whereas other oxidants had no significant effect.
      Isolated colonocyte membranes were found to contain considerable amount of
      nonesterified fatty acids as part of the total lipids and removal of free fatty
      acids from the membrane using fatty acid-free albumin made the membranes
      susceptible to iron-induced free radical generation and lipid peroxidation. These
      studies suggest that colonocytes are possibly protected from lipid peroxidation
      by the free fatty acids associated with the membrane.

PMID- 7642207
TI  - Effect of calcium ion on Hydrilla verticillata thylakoid membrane O2 evolution.
AB  - Calcium ion-dependent reactivation of O2 evolution activity has been investigated
      in Hydrilla verticillata thylakoid preparations. Washing the thylakoids in
      calcium-free buffer or calcium-free buffer containing 1.5 M NaCl or 1.5 M NaCl
      plus 20% methanol, reversibly inhibited O2 evolution activity. The activity was
      restored on addition of calcium as calcium chloride and partially by strontium
      chloride. Immobilization of thylakoids with glutaraldehyde (GA) arrested the loss
      in O2 evolution activity caused by calcium-free high salt washing. However,
      calcium sensitivity was discernible in GA immobilized thylakoids subjected to
      calcium-free high salt washing. Since glutaraldehyde checks the loss of extrinsic
      thylakoid polypeptides due to washing, it is assumed that the calcium ion has
      regulatory functions in the photosynthetic electron transport, besides its
      interaction with thylakoid proteins.

PMID- 7642208
TI  - The effect of a single amino acid substitution within the V3 loop of HIV-1 gp120
      on HLA-DR1-restricted CD4 T-cell recognition.
AB  - Viral variation has been proposed to play a role in the pathogenesis of human
      immunodeficiency virus type-1 (HIV-1) infection, and is an important
      consideration in vaccine design. During the course of an infection, isolates with
      sequence changes in CD8 T-cell and B-cell epitopes arise. To determine whether
      sequence variation within the V3 loop of HIV-1 gp120 affects HLA-DR beta 1*0101
      restricted CD4 T-cell recognition, we have generated CD4 T-cell clones (TLC)
      specific to gp120 V3 loop peptides. Four HLA-DR beta 1*0101-restricted groups of
      TLC were defined by distinct patterns of responses to a panel of peptides,
      consistent with a highly diverse T-cell repertoire recognizing the 30 amino acid
      stretch (296-326) of the gp120 V3 loop. Nevertheless, a single residue change at
      position 311 was found to abolish the recognition of two of the four groups of
      TLC. This was not due to an effect of the residue at 311 on binding to major
      histocompatibility complex (MHC), because: (1) irrespective of the residue at
      311, peptides competed well with the influenza haemagglutinin peptide 307-319 for
      binding to cell-bound DR1; and (2) R311-specific TLC were also HLA DR beta 1*0101
      restricted. Instead, the substitution of arginine for serine at position 311
      blocked the interaction of the peptide with the T-cell receptor. Thus, despite
      the diversity of the T-cell response to the V3 loop of HIV-1, a single amino acid
      change can have a considerable influence on the responding T-cell population. As
      residue 311 is one of the most variable of the V3 loop residues, these results
      suggest that CD4 recognition can also exert pressure on viral variation
      consistent with a role for these cells in antiviral immunity.

PMID- 7642209
TI  - Interaction of complement and specific antibodies with the external glycoprotein
      120 of HIV-1.
AB  - Previously we have investigated the interaction of human complement as well as
      one polyclonal and three human monoclonal antibody preparations with the human
      immunodeficiency virus type-1 (HIV-1) transmembrane recombinant glycoprotein
      (rgp41). A strong competition was found between the antibodies and deposited
      complement proteins for the same binding sites located within the immunodominant
      region of rgp41. The aim of the present experiments was to see if the same type
      of antibody-complement-HIV-1 interactions could be observed with the outer
      envelope glycoprotein (rgp120) of HIV-1. Three different glycosylated rgp120
      preparations, as well as a synthetic peptide corresponding to the V3 loop of the
      MN strain, were adsorbed to enzyme-linked immunosorbent assay (ELISA) plates and
      incubated with mixtures of anti-rgp120 antibodies and normal human serum (NHS) as
      a complement source. Fixed complement proteins and antibodies were detected with
      specific, peroxidase-labelled antibodies against different complement proteins
      (C1q, C4b, C3b) and the gamma-chain of antibodies. In the absence of anti-rgp120,
      high amounts of C3 were deposited to each rgp120 preparation tested (including
      the V3 peptide) but significant differences in the amounts of bound C1q and C4b
      were observed. Using sera deficient in different complement proteins, we found
      that both the classical and the alternative pathways contributed to the C3
      binding to rgp120. Addition of specific antibodies did not increase complement
      activation by rgp120 and only in the case of a monoclonal antibody to the V3-loop
      could we see complement-dependent inhibition of antibody binding.

PMID- 7642210
TI  - Importance of the third thrombospondin repeat of C6 for terminal complement
      complex assembly.
AB  - The anti-C6 monoclonal antibody WU 6-4 was shown to be unequivocally native
      restricted since it neither binds to the terminal complement complex (TCC) nor to
      C5b6. In addition, it was shown to inhibit TCC formation by interfering with C5b6
      generation. Using the pUEX expression system and C6 cDNA the WU 6-4 epitope was
      mapped to the third thrombospondin repeat of C6. This protein domain may
      therefore contribute to the C5 binding site of C6 and be involved in terminal
      complement complex assembly. The presence of the epitope in rabbit C6 indicates a
      useful model for studying inhibition of TCC formation in vivo.

PMID- 7642211
TI  - Germ-line human epsilon heavy chain gene RNA transcripts utilize the full range
      of alternative 3' splicing seen in productive epsilon mRNA.
AB  - An early step in immunoglobulin isotype switching involves the initiation of
      active transcription of downstream heavy chain loci while they are still in germ
      line configuration. This results in the production of 'sterile' germ-line RNA
      transcripts that do not contain VDJ sequences, the role of which in isotype
      switching is under intense scrutiny. We investigated whether such human epsilon
      germ-line transcripts employ the full complement of complex alternative 3' RNA
      splicing, splicing we have recently reported occurring with productive epsilon
      mRNA transcripts. Using a reverse transcriptase polymerase chain reaction (RT
      PCR) strategy, in which the 5' primer was located in the I region of the epsilon
      gene, a region expressed in germ-line but not productive (VDJ containing) epsilon
      transcripts, we showed that the full range of alternative 3' epsilon splices
      occur with germ-line transcripts. These results demonstrate that epsilon 3'
      splicing events are independent of 5' isotype DNA switching. Additionally, we
      showed that, just as with mature epsilon mRNA, the relative production of the
      various epsilon germ-line mRNA isoforms was responsive to modulation by stimuli
      such as interleukin-10 (IL-10). Thus B cells, when stimulated to produce epsilon
      germ-line transcripts, generate a family of germ-line mRNA that differ not only
      in their initiation sites but, more importantly, also differ in their 3'
      sequences, sequences that could be important in regulation of the parent gene
      itself. Furthermore, by discontinuous or trans-splicing, cells could utilize
      these various epsilon germ-line transcripts to produce the full range of mature
      IgE proteins prior to undergoing deletional recombination of isotype switching.

PMID- 7642212
TI  - Soluble, but not immobilized, anti-IgM antibody inhibits post-activation events
      leading to T-cell-dependent B-cell differentiation.
AB  - The potential for surface immunoglobulin-binding ligands to modify B-cell
      differentiation responses induced by activated T cells has been investigated.
      Activated T cells in human splenic mononuclear cells cultured on anti-CD3-coated
      plates induced B cells to produce large amounts of IgM and IgG. In this
      experimental system, cross-linking of B-cell antigen receptors by soluble,
      bivalent monoclonal or polyclonal anti-IgM antibodies completely inhibited IgM
      production, and greatly diminished IgG production, in a dose-dependent manner.
      Similar results were obtained using a F(ab')2 fragment of a goat anti-IgM
      antibody. Inhibition of B-cell differentiation by bivalent cross-linking reagents
      did not require the presence of antigen-presenting cells (APC), as comparable
      results were obtained in co-cultures of purified T and B cells. In contrast,
      enhanced immunoglobulin secretion was seen when surface IgM was cross-linked
      using anti-IgM antibody immobilized on the culture plate. Interestingly,
      activated T cells induced similar levels of expression on B cells of the
      activation antigens CD23, CD25 and CD71, and of class II molecules, irrespective
      of any treatment with soluble or immobilized anti-IgM antibody. This indicates
      that soluble anti-IgM specifically inhibits B-cell differentiation without
      altering initial events of T-cell-dependent B-cell activation.

PMID- 7642213
TI  - A monoclonal antibody against a murine CD38 homologue delivers a signal to B
      cells for prolongation of survival and protection against apoptosis in vitro:
      unresponsiveness of X-linked immunodeficient B cells.
AB  - A novel monoclonal antibody (mAb) was established in an attempt to look for a
      cell-surface molecule that delivered a signal regulating apoptotic cell death of
      B cells. Because spleen cells in resting culture die from apoptosis, mAb were
      looked for that were able to prolong spleen cell survival in vitro. This
      screening selected mAb CS/2. CS/2 not only prolonged spleen cell survival in
      vitro, but also protected spleen cells from apoptotic cell death brought about by
      irradiation or dexamethasone. Moreover, stimulation of spleen cells with CS/2 mAb
      induced changes of cells to blastoid morphology, and a significant uptake of
      [3H]thymidine ([3H]TdR). The antigen recognized by CS/2 mAb (CS/2 Ag) was
      expressed on preB cells, B cells, and Mac-1+ cells. The cells surviving in vitro
      culture or irradiation in response to ligation with CS/2 mAb were mostly B cells
      expressing the CS/2 Ag. In addition, B cells from X-linked immunodeficient (XID)
      mice did not respond to CS/2 mAb. These results indicate that CS/2 mAb is
      agonistic to B cells, and that XID mice are deficient in this CS/2 mAb-mediated
      activation pathway. Determination of the amino-terminal 24 amino acid residues
      revealed that the CS/2 Ag appears to be identical to the CS/2 mAb is directed
      against a murine CD38 homologue, and suggest a possible role of the murine CD38
      homologue in controlling apoptotic cell death of B cells.

PMID- 7642214
TI  - IgE production, antigen-induced airway inflammation and airway hyperreactivity in
      the brown Norway rat: the effects of ricin.
AB  - Ricin has been shown to enhance IgE production in the rat, probably through
      inhibition of suppressor T lymphocytes. We have studied further the effects of
      ricin on IgE titre and have determined its effects on antigen-induced airway
      inflammation and hyperreactivity in the Brown Norway rat. Immunization with
      ovalbumin (1-100 micrograms, intraperitoneally) produced dose-related increases
      in serum antigen-specific IgE titre. Ricin augmented the total IgE titre and
      caused about a 10-fold increase in the peak antigen-specific IgE titre. In
      sensitized animals, antigen challenge (three times with aerosolized ovalbumin
      every second day) caused a significant influx of eosinophils and neutrophils and
      significant airway hyperreactivity 24 hr after the third challenge. In sensitized
      animals that had also received ricin, the eosinophil and neutrophil influx was
      further significantly potentiated and a significant influx of lymphocytes also
      occurred. Thus, there was a relationship between the degree of sensitization and
      the magnitude of the inflammatory response. However, the enhanced airway
      inflammation in ricin-treated animals was not accompanied by a further
      enhancement of airway hyperreactivity. The present study demonstrates that ricin
      enhances IgE production and augments an antigen-induced inflammatory pathology
      but does not potentiate antigen-induced airway hyperreactivity.

PMID- 7642215
TI  - Anti-dsDNA antibodies cross-react with ribosomal P proteins expressed on the
      surface of glomerular mesangial cells to exert a cytostatic effect.
AB  - Affinity-purified human polyclonal anti-double-stranded DNA antibodies (anti
      dsDNA) exerted a cytostatic effect towards human and rat glomerular mesangial
      cells (MC). In order to identify the cognate antigens for anti-dsDNA on the
      surface of MC, we used these autoantibodies to probe a human renal lambda gt11
      cDNA expression library. Two cDNA clones encoding the cognate proteins for the
      autoantibodies were isolated. Sequencing analysis of the two cDNA showed that
      they had 98.6% homology with the gene of the P0 and 99.2% homology with the gene
      of the P1 human acidic ribosomal phosphoproteins (P protein). Two galactosidase
      fusion proteins (125,000 and 150,000 MW) derived from the two cDNA inserts
      expressed in lysogenic Escherichia coli Y1089 could react with the original
      screening antibodies in an immunoblotting analysis. After transformation and
      expression of the full-length P1 clone in prokaryotic cells, the purified P1
      protein was able to react with anti-dsDNA. In a cross-inhibition experiment, the
      dsDNA binding activity of anti-dsDNA was inhibited by a synthetic polypeptide
      corresponding to the carboxyl-terminal 20 amino acids of P protein and purified
      P1 protein in a dose-dependent manner, but this was less potent than the
      inhibition caused by calf thymus dsDNA. By use of well-defined systemic lupus
      erythematosus (SLE) sera, we found only sera containing a high titre of anti
      dsDNA activity (> 300 IU/ml) reacted with P1 of rat MC lysate. Furthermore, the
      38,000 and 19,000 MW macromolecules were proved to be the cognate antigens for
      anti-dsDNA expression on the surface of the MC, by Western blot of the MC plasma
      membrane lysates. These results suggest that anti-dsDNA may cross-react with
      ribosomal P proteins expressed on the surface of the MC and exert cytostasis
      towards these cells.

PMID- 7642216
TI  - Breakdown of self-tolerance by intrathymic injection of a T-cell line inducing
      autoimmune gastritis in mice.
AB  - Autoimmune gastritis (AIG) develops spontaneously in BALB/c mice thymectomized 3
      days after birth (3d-Tx). We first confirmed our previous observations that CD4+
      splenic T cells in AIG mice induced AIG in nu/nu mice, while those in normal mice
      suppressed the development of the disease. In addition, we found that a
      quantitative balance between these effector (Te) and suppressor (Ts) T cells
      determined either onset or prevention of the disease. Peripheralization of Ts
      seemed to begin around 3 days after birth, since the incidence of AIG in mice
      that underwent Tx 6 days after birth (6d-Tx) decreased markedly, compared with
      that of 3d-Tx mice; 12% in the former, while 79% in the latter. Notably, Ts
      existed in the 6d-Tx mice that escaped AIG. We next examined the target
      specificity of such Ts using syngeneic parietal cells known as autoantigens and
      two kinds of T-cell lines established from an AIG mouse; one is gastritis
      inducible in vivo, termed A-II, while another is not, named AC-II. Intrathymic
      injection of parietal cells into mice 3 days after birth followed by 6d-Tx
      completely prevented the development of AIG. In contrast, injection of irradiated
      A-II, but not AC-II cells resulted in AIG in 67% of the mice. No autoimmune
      oophoritis (AIO) was induced in female mice, implying that the breakdown of
      tolerance is organ specific. Taken together, peripheral tolerance for organ
      specific autoantigens seems to be maintained by CD4+ Ts responding to Te, which
      induces the disease.

PMID- 7642217
TI  - Major long-term changes in gamma delta T-cell receptor-positive and CD2+ T-cell
      subsets after neonatal thymectomy in the pig: a longitudinal study lasting nearly
      2 years.
AB  - Blood leucocyte subsets in neonatally (20-day-old) thymectomized (Tx) and sham
      thymectomized (STx) pigs were analysed 13 times over nearly 2 years. Tx piglets
      showed a persistent selective leucopenia, due mainly to a approximately 95%
      reduction in gamma delta null T cells which fell, with a circulating half-life of
      approximately 2 weeks, to approximately 0.3 x 10(6)/ml. This residual population
      was extrathymic in origin since it increased numerically at least approximately
      eightfold as the Tx pigs grew. Changes in other subsets were complex and affected
      by antigenic experience associated with weaning and with a change of
      accommodation at approximately 4 months postoperation (p.o.). Most major
      populations were increased long-term after thymectomy, especially after 3 months
      p.o. [i.e. surface (s)IgM+ B cells and CD2+, CD8+, major histocompatibility
      complex (MHC) class II+, CD4+ and double-positive CD4+ CD8+ T-cell subsets].
      However, during the first 3 months, thymectomy caused a significant delay in
      development of CD8high and CD4+ T cells and, after 4 months p.o., a continuing
      lack of CD4only (single-positive) T cells. Fortuitous environmental antigenic
      stimulation caused a major transient lymphocytosis, with counts increasing 1.2
      fold in STx and 3.5-fold in Tx pigs. This was largely due to an increase in CD2+
      CD8+ MHC class II+ T cells, particularly in Tx pigs. The small residual thymus
      independent gamma delta null subset also increased, while gamma delta T cells in
      STx pigs actually decreased. Evolving changes in expression of CD45, CD45R, CD44,
      CD18 and very late antigen type-4 (VLA-4) also occurred following thymectomy.
      Thus, the most persistent long-term effect of thymectomy, other than the lack of
      gamma delta null T cells, was the markedly increased numbers of double-positive
      (CD4+ CD8low) T cells, most of which expressed MHC class II and higher levels of
      adhesion molecules.

PMID- 7642218
TI  - Occurrence of interleukin-5 production by CD4- CD8- (double-negative) T cells in
      lungs of both normal and congenitally athymic nude mice infected with Toxocara
      canis.
AB  - We studied cells in the lungs of BALB/c and BALB/c-nu/nu (nude) mice infected
      with Toxocara canis, which produced interleukin-5 (IL-5) in in vitro culture with
      larval excretory-secretory antigen (ESAg). The proportion of CD4+/CD8+/CD4- CD8-
      cells in lungs of both BALB/c and nude mice was unchanged before and after
      infection with T. canis. Panning and complement-mediated lysis using monoclonal
      antibody (mAb) to CD4 showed that CD4+ cells in the lung from both mice produced
      IL-5. Anti-CD4 mAb suppressed ESAg-stimulated IL-5 production in vitro. In vitro
      depletion or inhibition of CD8+ cells reduced IL-5 production significantly in
      some cases, suggesting involvement with IL-5 production. Anti-CD3 mAb enhanced IL
      5 production when incubated with or without ESAg. Production of IL-5 was reduced
      by in vivo depletion of CD4+ cells only and both CD4+ and CD8+ T cells, by
      intraperitoneal injection with appropriate mAb; IL-5 production was stimulated by
      anti-CD3 mAb. In contrast, IL-5 production by lung cells of BALB/c mice decreased
      by more than 90% after simultaneous injection with anti-CD4, anti-CD8 and anti
      CD3 mAb, and was not enhanced by anti-CD3 mAb. Similar results were obtained in
      nude mice. These results suggest that CD4- CD8- T cells, as well as CD4+ T cells,
      produce IL-5.

PMID- 7642219
TI  - Developmental changes predispose the fetal thymus to positive selection of
      CD4+CD8- T cells.
AB  - Selection of a competent T-cell repertoire is dependent on complex interactions
      between immature thymocytes and components of the thymic stroma. These events may
      be preserved in vitro by excising developing thymus rudiments and maintaining
      them under carefully controlled conditions in fetal thymus organ cultures (FTOC).
      Using this approach, we have shown that the ability of C57B1/6 thymi to sustain
      positive selection of mature CD4+CD8- cells is profoundly influenced by the day
      of gestation on which they are excised: while thymocytes from day 14 rudiments
      fail to progress beyond the CD4+CD8+ stage of the developmental pathway, day 15
      and day 16 thymi support the differentiation of CD4+CD8- thymocytes. Importantly,
      day 16 thymocytes transferred to day 14 deoxyguanosine-treated rudiments are
      likewise arrested at the CD4+CD8+ stage, suggesting that the thymic
      microenvironment of day 14 rudiments, rather than the state of differentiation of
      the thymocytes they contain, is responsible for the block in positive selection.
      Our studies of the stromal elements of day 14 rudiments have, however, revealed
      no obvious deficiencies in the cell types represented, or their expression of
      class II major histocompatibility complex (MHC) determinants. Furthermore, we
      have been unable to circumvent the blockage in positive selection by the addition
      of certain cytokines expressed late during gestation. These results suggest that
      subtle changes occurring at day 15 of ontogeny render the thymic microenvironment
      capable of positive selection.

PMID- 7642220
TI  - Protein kinase C isoform expression in CD45RA+ and CD45RO+ T lymphocytes.
AB  - Differences in levels of specific enzymes utilized in intracellular signalling
      could be a factor in the distinct signalling properties observed in memory and
      naive T cells. We have studied the expression of both classical and non-classical
      protein kinase of C (PKC) isoenzymes in CD45RA and CD45RO cells using a
      combination of Western blot and flow cytometric analysis. These data indicate
      that CD45RA cells express higher levels of PKC alpha, PKC beta and PKC delta than
      CD45RO cells. In addition, CD45RA+ cells show greater proliferative activity when
      stimulated with phorbol myristate acetate (PMA) and calcium ionophore than their
      CD45RO+ counterparts. Variations in the levels of these isoenzymes could be
      implicated in functional differences, such as proliferation and cytokine
      production, in these cell subsets.

PMID- 7642221
TI  - Tyrosine phosphatase antagonist-induced activation of the neutrophil NADPH
      oxidase: a possible role for protein kinase C.
AB  - To investigate the role of tyrosine phosphorylation in polymorphonuclear
      leucocyte (PMN) activation we have examined the effect of the potent tyrosine
      phosphatase (PTPase) inhibitor, vanadyl hydroperoxide, on PMN function. Western
      blotting of vanadyl hydroperoxide-treated PMN showed that there was a rapid dose
      dependent increase in tyrosine-phosphorylated proteins. Vanadyl hydroperoxide
      also induced superoxide production in PMN over the range 10-100 microM, similar
      to the concentrations that also induced tyrosine phosphorylation. The tyrosine
      kinase inhibitor erbstatin totally inhibited the respiratory burst induced by
      vandyl hydroperoxide, showing that tyrosine kinase activity was necessary for
      superoxide production. The protein kinase C (PKC) inhibitors chelerythrine and
      bisidolylmaleimide inhibited the vanadyl hydroperoxide-induced respiratory burst
      with an inhibitory concentration of 50% (IC50) close to that for PKC inhibition
      without affecting tyrosine phosphorylation. These results indicate a possible
      role for PKC in vanadyl hydroperoxide-mediated superoxide production, and that
      any PKC involvement is downstream of tyrosine phosphorylation. These results
      further demonstrate that inhibition of phosphotyrosine phosphatases results in
      the activation of a functional response, indicating a critical role for
      phosphotyrosine phosphatases in PMN stimulation.

PMID- 7642222
TI  - IL-10 augments CD23 expression on U937 cells and down-regulates IL-4-driven CD23
      expression on cultured human blood monocytes: effects of IL-10 and other
      cytokines on cell phenotype and phagocytosis.
AB  - The effects of human recombinant interleukin-10 (IL-14) on the expression of
      several markers on U937 and human peripheral blood monocytes was studied by
      immunofluorescence and fluorescence-activated cell sorter (FACS) analysis. IL-10
      augmented Fc IgE receptor (Fc epsilon RII/CD23) further enhanced by cotreatment
      with IL-4 or interferon-gamma (IFN-gamma). In contrast, the basal level of Fc
      epsilon RII expression on blood monocytes appeared to fall in response to IL-10,
      and this effect became more evident on IL-4-treated cells. Furthermore, the
      constitutive and IFN-gamma-triggered Fc gamma RI/CD64 expression was augmented on
      both monocytes and U937 cells. Thus the expression of Fc gamma RII/CD32, Fc
      gamma/RIII/CD16, Fc alpha R/CD89, the receptor for complement components
      (CR1/CD35, CD3/CD11b, CR4/CD11c) and the receptor for transferrin/CD71 was not
      significantly influenced on IL-10-treated cells. IL-10 modestly triggered CD14
      antigen expression on monocytes but not U937. The expression of intercellular
      adhesion molecule-1 (ICAM-1)/CD54 on monocytes was significantly inhibited by IL
      10. As expected, a marked reduction of the constitutive as well as of the IFN
      gamma or IL-4-driven expression on HLA-DR, HLA-DP and HLA-DQ was observed on IL
      10-cultured monocytes. On the other hand, the expression of major
      histocompatibility complex (MHC) class I molecules was slightly and dose
      dependently induced on IL-10-treated monocytes. The ability of blood monocytes to
      phagocytose IgG-sensitized ox erythrocytes, and to bind and ingest opsonized
      Escherichia coli or latex particles, was amplified by IL-10. Our data demonstrate
      that IL-10 modulates the expression of a wide variety of structures on human
      mononuclear phagocytes, and augments their phagocytic capacity.

PMID- 7642223
TI  - Endotoxin and interferon-gamma differentially regulate the transcriptional levels
      of proto-oncogenes and cytokine genes during the differentiation of colony
      stimulating factor type-1-derived macrophages.
AB  - The expression of cytokine genes for interleukin-1 (IL-1) (alpha and beta) and
      tumour necrosis factor-alpha (TNF-alpha), along with the proto-oncogenes c-fos, c
      fms and c-myc, was examined by nuclear run-off and Northern blot analysis during
      in vitro differentiation of colony-stimulating factor type-1 (CSF-1)-derived bone
      marrow macrophages (BMDM). Constitutive transcription of c-myc was maximal on day
      3 and decreased with differentiation. Constitutive transcription of c-fms and c
      fos was similar at all times examined. In contrast, the steady-state mRNA levels
      were maximal on day 5 for c-myc and day 7 for c-fms and c-fos. Thirty minutes
      after endotoxin (lipopolysaccharide; LPS) stimulation, there was a rapid increase
      in run-off transcription rates for c-myc in day 3-day 9 BMDM, with maximal levels
      observed in day 7 BMDM. c-fms transcription was maximally induced within 1 hr by
      LPS in day 3 and day 5 BMDM. LPS induced transcription of c-fos to equivalent
      levels in day 3-day 9 BMDM. LPS stimulation augmented steady-state mRNA levels
      for c-myc, c-fms and c-fos. Maximal induction of c-myc was observed in day 3
      BMDM. c-fos and c-fms were both maximally induced in day 5 and day 7 BMDM.
      Interferon-gamma (IFN-gamma) had no effect on transcription of the proto
      oncogenes examined. In contrast to the proto-oncogenes, peak levels of run-off
      transcription for IL-1 alpha and IL-1 beta genes were observed 1-2 hr after LPS
      stimulation for day 3, day 5 and day 7 BMDM. The kinetics of LPS-induced steady
      state mRNA accumulation of IL-1 alpha and IL-1 beta were similar to the kinetics
      of run-off transcription. Constitutive transcription of TNF-alpha was observed on
      all days of differentiation. LPS and IFN-gamma both enhanced run-off
      transcription of the TNF-alpha gene; however, LPS had a more pronounced effect.
      The kinetics of induction of TNF-alpha transcription paralleled the kinetics of
      steady-state TNF-alpha mRNA accumulation. IFN-gamma resulted in secretion of TNF
      alpha in day 5, day 7, and day 9 BMDM after 4-8 hr of stimulation. Day 3 BMDM had
      little, if any, secreted TNF-alpha activity.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7642224
TI  - Tyrosine kinase-dependent and -independent events induced by interleukin-2
      stimulation: interleukin-2-mediated NO production required for the induction of
      lymphokine-activated killer cell activity in rat splenocytes is tyrosine kinase
      independent.
AB  - Nitric oxide (NO) has recently been shown to be an indispensable co-factor in the
      generation of lymphokine-activated killer (LAK) cells induced by interleukin-2
      (IL-2). Upon stimulation with IL-2, cells endowed with specific receptors undergo
      phosphorylation of substrates mediated by protein tyrosine kinases (PTK). In this
      work we utilized a well-characterized PTK inhibitor, genistein (GEN), to address
      the role of PTK on NO-dependent LAK cell generation. The effects of GEN were
      tested on the expression of the inducible NO synthase (iNOS) gene, proliferation,
      generation of cytotoxic activity and production of NO upon IL-2 stimulation of
      rat splenocytes. We report here that GEN displays profound inhibitory effects on
      recombinant (r)IL-2 induced proliferation and on LAK cell generation, while only
      marginally affecting NO production, measured as NO2-. In contrast, a specific
      inhibitor of the NO synthetic pathway (NG-monomethyl-L-arginine; NMMA) blocked
      generation of LAK cells and NO production without affecting cell proliferation.
      If added directly to the cytotoxicity tests, GEN exerted minor inhibitory
      effects, not exceeding 25% of control tests, while NMMA was completely
      ineffective. Sodium nitroprusside (SNP), a non-enzymatic NO-releasing substance,
      restored LAK cell generation in cultures performed in the presence of NMMA, but
      not in those performed in the presence of GEN. These results indicate that IL-2
      induced NO production is a PTK-independent event. IL-2-stimulated LAK cell
      generation obligatorily requires the concurrent activation of PTK dependent and
      independent signal transduction pathways.

PMID- 7642225
TI  - IL-2 and IL-7 but not IL-12 protect natural killer cells from death by apoptosis
      and up-regulate bcl-2 expression.
AB  - Human natural killer cells (NK) respond to interleukin-2 (IL-2) with augmented
      cytolytic activity, cytokine secretion and cell proliferation. Here we show that
      IL-2 protects NK cells from death by apoptosis (programmed cell death; PCD).
      Highly purified NK cells (CD3- CD56+) were isolated from peripheral blood
      lymphocytes (PBL) of either control donors or of an asymptomatic donor with 60%
      NK cells. Glucocorticosteroids (GCS) induced PCD in NK cells, as shown by nuclear
      condensation and DNA fragmentation. IL-2 completely prevented GCS-induced PCD in
      a dose-dependent manner without overcoming GCS-induced inhibition of NK cell
      proliferation. The IL-2 protective effect was mediated through the p75 beta chain
      of the IL-2R, as neutralizing monoclonal antibody (mAb) to the p75 beta chain but
      not to the p55 alpha chain completely abolished the IL-2 anti-apoptotic activity.
      In addition to IL-2, the cytokines IL-7 and IL-12 have been reported to regulate
      NK cell functions. Our present data showed that IL-7 but not IL-12 rescued NK
      cells from apoptosis, but to a lesser extent than IL-2. Although IL-4 had a
      marginal protective effect, IL-1, IL-3, IL-6, IL-8, interferon-gamma (IFN-gamma)
      and IFN-alpha, tumour necrosis factor-alpha (TNF-alpha), transforming growth
      factor-beta (TGF-beta) and granulocyte-macrophage colony-stimulating factor (GM
      CSF) displayed no significant activity. Finally, we report that IL-2 and IL-7
      enhanced bcl-2 expression in NK cells, suggesting the existence of a bcl-2
      dependent survival pathway. In addition to regulating various functions, it is
      concluded that IL-2 and IL-7 have the ability to prevent PCD in NK cells.

PMID- 7642226
TI  - Early-appearing tumour-infiltrating natural killer cells play a crucial role in
      the generation of anti-tumour T lymphocytes.
AB  - Natural killer (NK) cells that infiltrated into the primary tumour site at an
      early stage of tumour development, were examined for their participation in the
      generation of anti-tumour cytotoxic T lymphocytes (CTL). NK cells, which were
      detected by anti-NK1.1 monoclonal antibody (mAb), increased in the peritoneal
      exudate cells (PEC) on days 3 and 7 after an intraperitoneal (i.p.) inoculation
      of syngeneic B16 melanoma cells. These tumour-infiltrating NK cells showed a high
      level of cytotoxic activity against NK-sensitive YAC-1 cells and an increased
      expression of interferon-gamma (IFN-gamma) mRNA and interleukin-2 (IL-2) mRNA.
      The in vivo depletion of NK cells with anti-NK1.1 mAb, prior to i.p. inoculation
      of B16 melanoma cells, resulted in an increased number of tumour cells in the PEC
      compared to NK cell non-depleted mice. Interestingly, the differences in tumour
      cell number between both groups were more prominent on days 7 and 14 than on day
      3, which strongly suggested that early-infiltrating NK cells have a large
      influence on the subsequent anti-tumour response. The in vivo depletion of NK
      cells prior to immunization with melanoma cells abrogated the capacity of the
      spleen cells to generate CD8+ tumour-specific CTL after in vitro restimulation.
      This inability of generating anti-tumour CTL was partially restored by additional
      i.p. injections of recombinant IL-2 and/or IFN-gamma simultaneously with the
      immunization of melanoma cells. The in vitro depletion of NK cells prior to the
      in vitro restimulation with melanoma cells partially impaired the anti-tumour CTL
      generation from the spleen cells of the immunized mice. Lastly, the in vivo
      depletion of NK cells prior to immunization with melanoma cells abolished the
      protective immunity against melanoma cells at the rechallenge. Overall, these
      results indicate that early-appearing tumour-infiltrating NK cells not only
      participate in the anti-tumour early defence by themselves, but also play a
      crucial role in the generation of anti-tumour CTL.

PMID- 7642227
TI  - Evolution of V genes: DNA sequence structure of functional germline genes and
      pseudogenes.
AB  - In this review we have examined the features of germline sequences of IgV genes
      from a number of species in an attempt to identify the "signature" of molecular
      mechanisms responsible for generating and maintaining diversity in the germline
      repertoire (after gene duplication by meiotic unequal crossover). We now
      summarize the relevant features point by point: 1. Codon analysis reveals a
      significant deficit of stop codons below the numbers that would be expected under
      random point mutational change. This implies that the majority of individual V
      genes have each been selected for the possession of open reading frames able to
      encode a functional Ig molecule. There is an extraordinarily high rate of
      apparent rescue of potential stop codons in both V genes and pseudogenes. Other
      (non-Ig) pseudogene sequences studied thus far do not show this high rate of
      rescue of stop codons. 2. The distribution of changes is concentrated in most
      cases in the 5' half of CDR2 (CDR2a), and coincides with the patterns of antigen
      selected mutations in B lymphocytes. It does not coincide with expected non
      antigen-selected (random) changes, as exemplified by hypermutated but unexpressed
      passenger V transgenes in B cells in Peyer's patches of unimmunized mice
      (Gonzalez-Fernandez and Milstein 1993). 3. In germline V genes of mice, there is
      no evidence of triplet codon insertion (or multiples thereof) as a mechanism
      generating germline diversity. This parallels a known absence of gene conversion
      as a mechanism generating somatic diversity in mice. In contrast, in germline
      chicken pseudogenes which are known to contribute to somatic generation of
      diversity by gene conversion, frequent examples of triplet codon insertions and
      deletions in CDRs are present. 4. The pattern of unique insertions and deletions
      in all species with sufficient sequence data available is consistent with hyper
      recombination events targeting the transcription and/or coding unit. The
      distribution of these events does not correlate with known inducers of gene
      conversion, for example, inverted or direct repeats and palindromes. Furthermore,
      the 5' boundaries of somatic hypermutation and the 5' peak of germline nucleotide
      insertions and deletions coincide in IghV (Rothenfluh et al. 1993, 1994; Rogerson
      1994) and in IgkV (Rogerson 1994; Rada et al. 1994, and analyses herein). It will
      be interesting to see how these features relate to each other in other gene sets
      as data become available.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7642228
TI  - L cells expressing DQ molecules of the DR3 and DR4 haplotypes: reactivity
      patterns with mAbs.
AB  - cDNAs coding for the HLA class II DR and DQ alpha and beta chains of the
      diabetogenic haplotypes DR3 and DR4 were introduced into a mammalian expression
      vector and transfected into L-cell mouse fibroblasts to produce cells expressing
      individual human class II molecules. Stable L transfectants were generated
      expressing each of the DR or DQ isotypes of the cis-encoded alpha and beta chains
      of the DR3 or DR4 haplotypes, as well as the trans-encoded alpha and beta chains
      of the DQ molecules of the two haplotypes. However, isotype mismatched
      combinations (DR alpha/DQ beta or DQ alpha/DR beta) did not result in any stable
      transfectants. The stable DQ L-cell transfectants obtained, along with homozygous
      B-cell lines expressing the DQ2 and DQ8 specificities, were tested against a
      large panel of twentyone anti-HLA class II monoclonal antibodies (mAbs). Their
      unusual reactivity patterns are described including the failure of most "pan-DQ"
      mAbs to react with all DQ expressing L-cell transfectants. Interestingly, some
      mAbs react with certain alpha beta heterodimers expressed on B-LCL but fail to
      recognize the same heterodimers expressed on the transfectants. This is
      suggestive of minor structural modifications that class II molecules undergo
      depending on the cells they are expressed on.

PMID- 7642229
TI  - Efficient nonhomologous and homologous recombination in scid cells.
AB  - The severe combined immunodeficiency (scid) mutation affects both coding joint
      formation during immunoglobulin and T-cell receptor V(D)J recombination and
      double-strand break repair. We analyzed scid cells for their ability to undergo
      other types of DNA end joining: nonhomologous and homologous recombination. Using
      plasmid constructs carrying antibiotic resistance genes, we observed that the
      efficiency of nonhomologous integration in scid cells was equal to that in
      wildtype cell lines. In addition, there was no obvious difference in the fidelity
      of the integration and in the expression of the resistance genes. Moreover, scid
      cells were able to carry out homologous recombination of extrachromosomal
      substrates just as well as wildtype cells. These results suggest a mechanistic
      difference between nonhomologous integration and homologous recombination on the
      one hand and V(D)J recombination and double-strand break repair on the other.

PMID- 7642230
TI  - The recombination activation gene 1 (RAG1) of rainbow trout (Oncorhynchus
      mykiss): cloning, expression, and phylogenetic analysis.
AB  - The characterization of genes involved in the generation of the immune repertoire
      is an active area of research in lower vertebrate taxa. The recombination
      activating genes (RAG) have been shown to be essential for V (D) J recombination
      of T-cell antigen receptor (TCR) and immunoglobulin (Ig) genes, leading to the
      generation of the primary repertoire. As RAG1 is critical to the differentiation
      of pre-B and -T cells, its expression within an associated primary lymphoid organ
      can serve as a developmental marker. To examine the ontogeny of lymphocytes in
      Oncorhynchus mykiss, we cloned RAG1 from trout and examined its tissue- and
      lymphocyte-specific expression. The polymerase chain reaction, coupled with
      degenerate oligonucleotide primers, was used to amplify a homologous probe [(633
      base pairs) (bp)] from rainbow trout genomic DNA, which in turn was used to
      isolate a lambda genomic clone. Sequence analysis of this genomic clone confirmed
      the RAG1 nature of this gene (3888 bp) and revealed an internal intron of 666 bp.
      When compared with other previously reported RAG1 sequences, the predicted amino
      acid translation (1073 aa) displayed a minimum of 78% similarity for the complete
      sequence and 89% similarity in the conserved region (aa 417-1042). Using northern
      blot analysis, we found the expression of RAG1 to be limited to surface Ig-n
      lymphocytes within the thymus. This data forms the basis for a proposal that the
      thymus of teleost species plays an essential developmental role in lymphopoiesis
      and thus can be regarded as a primary lymphoid organ.

PMID- 7642231
TI  - Duplication of the MHC-linked Xenopus complement factor B gene.
AB  - We have previously reported the molecular cloning of the mammalian major
      histocompatibility complex (MHC) class III gene, complement factor B (Bf) from
      Xenopus laevis, and linkage of the gene to the frog MHC. Here, we estimated the
      copy number of the Xenopus Bf gene by genomic Southern blotting analysis and
      demonstrated that Xenopus laevis has two copies of the Bf gene. Both genes co
      segregated with the MHC-linked HSP70 genes among 19 offspring of an f/r x f/r
      cross, indicating a close linkage of the two Bf genes to the frog MHC. Both genes
      are transcribed and contain open reading frames. When compared with the
      previously determined cDNA sequence (Xenopus Bf A), the predicted amino acid
      sequence of the second cDNA species (Xenopus Bf B) shows 82% overall identity.
      Polymerase chain reaction analysis indicated that all of the partially inbred
      frogs with the f, r, g, and j MHC haplotypes, as well as 12 outbred frogs tested
      have both Bf genes, suggesting that the duplicated Bf genes are stable genetic
      traits in Xenopus laevis.

PMID- 7642232
TI  - Identification and characterization of T-cell antigen receptor-related genes in
      phylogenetically diverse vertebrate species.
AB  - Characterization of the structure, multiplicity, organization, and cell lineage
      specific expression of T-cell receptor (TCR) genes of nonmammalian vertebrate
      species is central to the understanding of the evolutionary origins of
      rearranging genes of the vertebrate immune system. We recently described a
      polymerase chain reaction (PCR) strategy that relies on short sequence
      similarities shared by nearly all vertebrate TCR and immunoglobulin (Ig) variable
      (V) regions and have used this approach to isolate a TCR beta (TCRB) homolog from
      a cartilaginous fish. Using these short PCR products as probes in spleen cDNA and
      genomic libraries, we were able to isolate a variety of unique TCR and TCR-like
      genes. Here we report the identification and characterization of a chicken TCR
      gamma (TCRG) homolog, apparent Xenopus and pufferfish TCR alpha (TCRA) homologs,
      and two horned shark TCR delta (TCRD)-like genes. In addition, we have identified
      what could be a novel representative of the Ig gene superfamily in the
      pufferfish. This method of using short, minimally degenerate PCR primers should
      speed progress in the phylogenetic investigations of the TCR and related genes
      and lend important insights into both the origins and functions of these unique
      gene systems.

PMID- 7642233
TI  - Isolation and characterization of cDNA clones for Japanese quail (Coturnix
      japonica) major histocompatibility complex (MhcCoja) class I molecules.

PMID- 7642234
TI  - Cloning and sequencing of the rabbit gene encoding T-cell costimulatory
      molecules.

PMID- 7642235
TI  - Sequence and structure of the mouse ThB gene.

PMID- 7642236
TI  - Hamster cDNA homologs to the mouse immunoglobulin IgG2 constant and Igh-VH10
      genes.

PMID- 7642237
TI  - Hamster cDNA homologs to the mouse immunoglobulin kappa constant and Igk-V 45.1
      genes.

PMID- 7642238
TI  - Sequence divergence of B2m in different cattle populations.

PMID- 7642239
TI  - A new HLA-B35 allele (B*3510) found in isolated Jaidukama South American Indians.

PMID- 7642240
TI  - Helical (spiral) computed tomography. Implications for imaging of the abdomen.
AB  - Dramatic refinements in CT technology are resulting in improved evaluation of the
      liver, pancreas, and gastrointestinal tract. Further clinical trials are
      necessary to compare the relative merits of CT versus MR imaging and endoscopic
      ultrasonography in a wide variety of gastrointestinal diseases.

PMID- 7642241
TI  - Transjugular intrahepatic portosystemic shunts for portal hypertension.
AB  - TIPS has rapidly become a proven effective therapy for treatment of acute
      variceal bleeding and is probably an effective therapy for intractable ascites.
      Nonetheless, it is important to define the appropriate subpopulation best suited
      for the TIPS procedure. Given the poor long-term patency of TIPS and the need for
      close follow-up, TIPS is not an optimal therapy for an unreliable patient who is
      not a candidate for liver transplantation. In contrast, TIPS is especially useful
      in the patient anticipating liver transplantation soon after TIPS placement.
      Further study is needed to define the optimal use for TIPS.

PMID- 7642242
TI  - Magnetic resonance cholangiography.
AB  - MR cholangiography offers a noninvasive method of obtaining images of the biliary
      system without the use of a contrast agent. There is no radiation exposure. Pulse
      sequences can be chosen to obtain bright bile or black bile cholangiograms. Image
      processing algorithms can be selected to obtain a three-dimensional
      representation of biliary anatomy and pathology, and those images can be rotated
      in any plane so that ductal anatomy and pathology can be seen to best advantage.
      In patients with a nonobstructed biliary system, the RHD, LHD, CHD, CBD, and
      distal PD are usually visible. In patients with choledocholithiasis, the CE-FAST
      technique has demonstrated higher diagnostic accuracy than the FSE approach,
      although TRAP image reconstruction probably would improve the accuracy of the FSE
      technique in detecting stones. In patients with malignant biliary obstruction,
      FSE is considerably more accurate in determining the cause of obstruction than is
      CE-FAST. Furthermore, MR cholangiography compares favorably with ERCP, prompting
      one author to suggest that, in selected patients, MR cholangiography might be
      used instead of direct cholangiography or to direct invasive techniques. With
      continued technologic advancements, MR cholangiography will no doubt improve as
      well. In particular, the possibility of a breath-hold, multicoil, FSE
      cholangiogram, obtained with the stronger gradients on an echo planar system,
      potentially combines the key advantages of CE-FAST and conventional FSE
      techniques. It may be that in the not-too-distant future, all patients with
      obstructive jaundice will be imaged first with MR imaging. In addition to the
      typical axial images of the abdomen required for staging, an MR cholangiogram
      will be obtained in a matter of a few seconds. An MR angiogram will also be
      performed to determine vascular anatomy and pathology. MR spectroscopy might also
      be used to obtain additional diagnostic information. All of this would be done in
      less than an hour, noninvasively, and with no radiation. Some patients would then
      require percutaneous transhepatic cholangiography or ERCP. Others would undergo
      MR-guided biopsy. Eventually, still other patients might go directly to surgery.

PMID- 7642243
TI  - Imaging after laparoscopic cholecystectomy.
AB  - Imaging for laparoscopic cholecystectomy involves preoperative imaging of the
      gallbladder and bile ducts, usually by sonography. Post-operative imaging is
      usually necessary only for suspected surgical complications. Cross-sectional
      imaging identifies most patients with postoperative complications.
      Cholangiography is needed to characterize all biliary abnormalities.
      Interventional radiologic techniques are helpful to aspirate or drain abdominal
      fluid collections, provide temporary biliary drainage, or cure cystic stump leaks
      or treat complications of choledochojejunostomy.

PMID- 7642244
TI  - Gallery of double-contrast terminology.
AB  - This article visually defines the descriptive terms commonly used in double
      contrast gastrointestinal radiology. The terms are organized by whether they
      primarily refer to mucosal, wall, or extrinsic abnormalities.

PMID- 7642245
TI  - Role of the double-contrast upper gastrointestinal series in the 1990s.
AB  - The double-contrast upper GI series makes medical and economic sense as a cost
      effective alternative to endoscopy for evaluating patients with dyspepsia or
      other upper GI symptoms who fail to respond to an empiric trial of medical
      therapy. These studies are capable of detecting most clinically significant
      disease in the upper GI tract. Furthermore, data indicate that double-contrast
      studies can achieve a high sensitivity in the diagnosis of malignant lesions
      without exposing an inordinate number of patients to unnecessary endoscopy. Thus,
      as we approach the twenty-first century, the upper GI series continues to be a
      valuable diagnostic test in modern medical practice.

PMID- 7642246
TI  - Guide to imaging of the small bowel.
AB  - The small intestine is a difficult organ to image. Its considerable length, the
      changing location of its many overlapping coils, and the often adverse effect of
      luminal fluids on the coating ability of barium necessitate the use of special
      techniques employing special barium formulations.

PMID- 7642247
TI  - Oral and pharyngeal dysphagia.
AB  - The swallowing tract extends from the lips to the gastric cardia. The barium
      swallow provides a global view of oral, pharyngeal, and esophageal motility and
      pharyngeal and esophageal morphology. Barium pharyngography is the best test to
      assess the functional capabilities of the pharynx. The barium swallow may be used
      as the sole diagnostic examination or as a guide to what procedure or
      intervention should be forthcoming.

PMID- 7642248
TI  - Radiologic investigation of acute inflammatory and infectious bowel disease.
AB  - Definitive diagnosis of infectious or idiopathic inflammatory bowel disease
      ultimately rests on histologic and bacteriologic documentation. Nevertheless,
      radiologic studies play an important role in the evaluation and management of
      patients with acute enterocolitis. Plain abdominal films can give a gross
      estimate of disease extent in the colon and detect complications, such as
      perforation or toxic megacolon. Double-contrast barium enema allows visualization
      of the mucosal pattern and the overall configuration of the bowel, which are
      important for determining the extent and severity of disease and its most likely
      cause. Cross-sectional imaging depicts the mural and mesenteric involvement as
      well as intraperitoneal complications of inflammatory bowel disease, thus
      providing a critically important perspective that complements the information
      afforded by endoscopic and conventional radiographic techniques.

PMID- 7642249
TI  - Endoscopic ultrasonography of the gastrointestinal tract.
AB  - Endoscopic ultrasonography (EUS) combines the advantages of conventional
      endoscopy with the capabilities of ultrasonography. EUS allows clinicians to see
      through the wall of the gastrointestinal tract. The close proximity allows the
      use of relatively high frequencies with the resulting increase in tissue contrast
      and resolution. Despite some limitations, this new modality does open new
      horizons in the diagnosis and characterization of upper gastrointestinal
      diseases.

PMID- 7642250
TI  - Gastrointestinal manifestations of AIDS.
AB  - As the AIDS epidemic continues to grow, it becomes increasingly important that
      physicians are aware of the gastrointestinal and abdominal diseases specific to
      this group of patients. Most AIDS patients exhibit gastrointestinal symptoms at
      some time during the course of their disease. Clinical AIDS is often determined
      by identifying an opportunistic infection or neoplasm of the gastrointestinal
      tract. Radiology often plays a key role in helping to determine the diagnosis as
      well as in directing the management.

PMID- 7642251
TI  - Magnetic resonance angiography of the abdomen.
AB  - The applications of abdominal MR angiography have been slow as compared with its
      applications in the head and neck mainly because of greater technical
      difficulties in dealing with respiratory motion and the use of the body coil,
      which has a poorer signal-to-noise ratio than head or surface coils. Further work
      is needed to reduce motion sensitivity and improve spatial resolution. Flow
      contrast and depiction of slowly flowing blood could be improved with the use of
      intravascular contrast agents. 52MR angiography is the imaging method of choice
      in the evaluation of the portal venous system, systemic veins, and aortic
      disease. With further technical improvements, it seems likely that applications
      of MR angiography will also be extended to smaller vessels.

PMID- 7642252
TI  - Functional properties of nonhuman primate antibody to Porphyromonas gingivalis.
AB  - The nonhuman primate (NHP) serves as a useful model for examining the host
      parasite interactions in Porphyromonas gingivalis-associated periodontal disease.
      This study determined the influence of NHP sera on (i) the direct killing of P.
      gingivalis, (ii) P. gingivalis-induced superoxide anion (O2-) release from human
      polymorphonuclear leukocytes (PMNs), and (iii) the ability of PMNs to bind and
      phagocytize P. gingivalis. Three types of NHP sera were utilized: (i) normal or
      baseline sera; (ii) sera obtained after ligature-induced periodontitis; and (iii)
      sera obtained following active immunization with formalinized P. gingivalis. All
      assays were performed with or without the addition of human complement.
      Significantly more (P < 0.01) direct killing of P. gingivalis occurred with
      immunized sera and complement than with any of the other treatments. The sera
      from ligature-induced periodontitis NHPs had significantly less (P < 0.03)
      killing capacity than the baseline sera, which contained natural antibody
      produced to P. gingivalis colonization. Sera from immunized NHPs were used to
      opsonize P. gingivalis and caused significantly greater (P < 0.01) levels of O2-
      release from PMNs. Finally, the sera from immunized NHPs significantly enhanced
      (P < 0.009) the uptake of P. gingivalis by PMNs, although binding of the bacteria
      to PMNs was similar among all three serum types. Active immunization of NHPs with
      P. gingivalis elicited a functional antibody that enhanced direct killing,
      positively influenced the activation of PMNs, and enhanced the ability of PMNs to
      phagocytize P. gingivalis. Moreover, antibody produced as a sequela of
      progressing periodontitis appeared to lack these functions. A wide variability in
      functional capacity of the sera from individual NHPs, which may contribute to an
      individual's susceptibility to P. gingivalis-induced disease, was noted. This
      variability suggested that results from functional tests of serum antibody may
      aid in predicting host susceptibility to disease and response to therapy.

PMID- 7642253
TI  - In vivo regulation of replicative Legionella pneumophila lung infection by
      endogenous tumor necrosis factor alpha and nitric oxide.
AB  - The in vivo role of endogenous tumor necrosis factor alpha (TNF-alpha) and
      reactive nitrogen intermediates (RNIs) in modulation of growth of Legionella
      pneumophila in the lung was assessed using a murine model of replicative L.
      pneumophila lung infection. Intratracheal inoculation of mice with L. pneumophila
      resulted in induction of endogenous TNF-alpha, which preceded clearance of L.
      pneumophila from the lung. Inhibition of endogenous TNF-alpha activity, via in
      vivo administration of TNF-alpha neutralizing antibody, or inhibition of
      endogenous RNIs, via administration of the nitric oxide (NO) synthetase inhibitor
      N-monomethyl-L-arginine (NMMA), resulted in enhanced growth of L. pneumophila in
      the lung at > or = 3 days postinfection (when compared with untreated L.
      pneumophila-infected mice). Because of the similar kinetics of enhanced pulmonary
      growth of L. pneumophila in mice treated in vivo with either anti-TNF-alpha
      antibody or NMMA, the immunomodulatory effect of NO on endogenous TNF-alpha
      activity in the lung was assessed. Administration of NMMA to L. pneumophila
      infected mice resulted in a significant decrease in endogenous TNF-alpha activity
      in the lung during replicative L. pneumophila infections in vivo. However,
      administration of exogenous TNF-alpha to NMMA-treated mice failed to
      significantly enhance clearance of L. pneumophila from the lung. Results of these
      studies indicate that both endogenous NO and TNF-alpha facilitate resolution of
      replicative L. pneumophila lung infections and that regulation of L. pneumophila
      replication by TNF-alpha is mediated, at least in part, by NO.

PMID- 7642254
TI  - Old mice are able to control low-dose aerogenic infections with Mycobacterium
      tuberculosis.
AB  - Previous work in this laboratory has led to the development of the hypothesis
      that the increased susceptibility of old mice to tuberculosis infection reflects
      a limited ability by immune CD4 mediator cells to accumulate at sites of
      bacterial implantation. To test this hypothesis with very low dose infections,
      the present study documented the course of a low-dose aerogenic infection with
      virulent Mycobacterium tuberculosis Erdman against time in the target organs of
      young (3-month-old) and old (24-month-old) B6D2F1 hybrid mice. The results of the
      study indicated that the infection was controlled by the two groups of mice at
      similar rates, although the bacterial load in the old mice was eventually
      somewhat higher. Despite these similarities, some subtle differences between the
      young and old mice were also evident and included evidence of increased
      hematogenous spread of the infection from the lungs to other organs in the old
      mice. Interestingly, very poor expression of the cytokine interleukin-12 was
      observed in the lungs of infected old mice, leading to the hypothesis that the
      poor CD4 response in such animals could be partially attributed to the lack of
      this Th1-type, CD4 T-cell-enhancing cytokine. In this regard, treatment of old
      mice with exogenous interleukin-12 increased resistance and promoted gamma
      interferon secretion by CD4 T cells from these mice, although the effects were
      generally modest. These data suggest that old mice possess CD4-independent
      compensatory mechanisms by which to deal with low-dose pulmonary tuberculosis
      infections, although such mechanisms are less efficient than those seen in young
      animals.

PMID- 7642255
TI  - Role of tumor necrosis factor alpha in innate resistance to mouse pulmonary
      infection with Pseudomonas aeruginosa.
AB  - In the present study, we have investigated the mechanisms underlying mouse
      resistance to endobronchial infection with Pseudomonas aeruginosa enmeshed in
      agar beads. This was done by monitoring macrophage activation-associated gene
      expression in lung and alveolar cells harvested from resistant (BALB/c) and
      susceptible (DBA/2, C57BL/6, and A/J) strains of mice over the course of
      infection with P. aeruginosa. Interleukin-1 alpha, interleukin-1 beta, macrophage
      inflammatory protein-1 alpha, JE, and tumor necrosis factor alpha (TNF-alpha)
      mRNA expression levels were up-regulated in all strains of mice during the early
      phase of the infection. The level of TNF-alpha mRNA expression was increased to a
      greater extent in resistant BALB/c mice than in susceptible DBA/2, C57BL/6, and
      A/J strains of mice. This observation paralleled a higher secretion of TNF-alpha
      into the alveolar space of BALB/c mice at 3 and 6 h postinfection. The
      concentration of TNF-alpha released in alveoli returned to basal levels within 24
      h of infection in mice of all strains, even though the TNF-alpha mRNA expression
      remained high until 3 days after infection. In vivo treatments with either anti
      murine TNF-alpha monoclonal antibodies or with aminoguanidine significantly
      increased the number of P. aeruginosa bacteria detected in the lungs of resistant
      mice at 3 days postinfection. Overall, these findings indicate that both TNF
      alpha and nitric oxide exert a protective role in response to pulmonary infection
      with P. aeruginosa.

PMID- 7642256
TI  - A recombinant Salmonella typhimurium vaccine induces local immunity by four
      different routes of immunization.
AB  - Immunization of mice with an attenuated Salmonella typhimurium strain (Phopc)
      carrying a plasmid encoding a hybrid form of the hepatitis B virus core antigen
      (HBc) induced specific antibody responses against the bacterial
      lipopolysaccharide (LPS) and HBc. Different mucosal routes of immunization, i.e.,
      oral, nasal, rectal, and vaginal, were compared for their ability to induce a
      systemic as well as a mucosal response at sites proximal or distant to the site
      of immunization. Anti-LPS and anti-HBc immunoglobulin A (IgA) antibodies were
      measured in saliva, in feces, and in genital, bronchial, and intestinal
      secretions. Specific antibodies in serum and secretions were observed after
      immunization via all routes; however, the response to LPS was independent of that
      against HBc. In serum, saliva, and genital and bronchial secretions, high amounts
      of anti-HBc IgA were obtained by the nasal route of immunization. Vaginal
      immunization resulted in two different responses in mice: high and low. We
      observed a correlation between the level of specific immune response and the
      estrous status of these mice at the time of immunization. Rectal immunization
      induced high amounts of IgA against HBc and LPS in colonorectal secretions and
      feces but not at distant sites. These data suggest that S. typhimurium is able to
      invade different mucosal tissues and induce long-lasting local IgA responses
      against itself and a carried antigen after a single immunization.

PMID- 7642257
TI  - Characterization of inhibitory effects of suspected periodontopathogens on
      osteogenesis in vitro.
AB  - By using an in vitro bone-forming culture system, the chick periosteal
      osteogenesis (CPO) model, the direct effects on osteogenesis of sonicated
      extracts derived from oral bacteria were examined. Both extracts from bacterial
      species having strong associations with periodontal diseases (Porphyromonas
      gingivalis, Actinobacillus actinomycetemcomitans, and Prevotella intermedia,
      hereinafter referred to as suspected periodontopathogens) and extracts from
      species not correlated with periodontal disease (Streptococcus sanguis,
      Veillonella atypica, and Prevotella denticola, hereinafter referred to as
      nonpathogenic bacteria) were tested. All bacterial cultures were grown under
      standard anaerobic culture conditions. Sonicated bacterial extracts were prepared
      from the bacterial pellet. These were added in various proportions to the CPO
      cultures. Parameters of osteogenesis, including alkaline phosphatase activity,
      calcium and P(i) accumulation, and collagen synthesis, were measured in 6-day-old
      cultures. Compared with controls grown in the absence of bacterial products,
      osteogenesis was inhibited significantly in cultures treated with extracts
      derived from the suspected periodontopathogens. No osteogenic inhibition was
      observed in cultures treated with extracts from the nonpathogenic bacteria. These
      results suggest that the ability to inhibit osteogenesis in vitro may be a
      pathogenic property shared by a limited group of species. Further
      characterization of the P. gingivalis extracts revealed that both proteinaceous
      and nonproteinaceous products, including lipopolysaccharide, were able to inhibit
      osteogenesis. P. gingivalis extract-mediated inhibition of osteogenesis in CPO
      cultures was blocked by indomethacin, implicating prostaglandins in the
      regulation of the bacterial effects. The bacterial extracts had either reversible
      or irreversible inhibitory effects on osteogenesis when added after
      differentiation or before/during differentiation of bone cells, respectively.

PMID- 7642258
TI  - Deletion of purE attenuates Brucella melitensis 16M for growth in human monocyte
      derived macrophages.
AB  - We constructed a defined purine-auxotrophic mutant of Brucella melitensis 16M by
      chromosomal gene replacement. We electroporated B. melitensis 16M with suicide
      plasmids containing a kanamycin resistance cassette that replaced 226 bp at the
      carboxyl end of purE, the intergenic region, and 18 bases of the purK open
      reading frame. Recombinant B. melitensis delta purE201 required exogenous purines
      for growth on minimal media. Purine auxotrophy was complemented by
      electroporation of B. melitensis delta purE201 failed to grow in human monocyte
      derived macrophages, while the growth of wild-type 16M and the complemented
      strain, delta purE201 (pSD5), increased by nearly two logs. These results suggest
      that B. melitensis delta purE201 will be attenuated in animals and humans and
      thus may be useful as a live attenuated vaccine.

PMID- 7642259
TI  - CD4+ T cells play a significant role in adoptive immunity to Chlamydia
      trachomatis infection of the mouse genital tract.
AB  - The ability of CD4+ and CD8+ T cells to adoptively immunize mice against
      Chlamydia trachomatis infection of the mouse genital tract was studied. Adoptive
      transfer experiments were performed with splenic CD4+ or CD8+ T cells obtained
      from mice following resolution of a primary genital tract infection and after a
      secondary chlamydial challenge. The results show that donor CD4+ T cells, but not
      CD8+ T cells, obtained from mice following resolution of a primary infection or
      after secondary challenge were effective in transferring significant
      antichlamydial immunity to the genital tracts of naive animals. The lymphokine
      profiles in the culture supernatants of proliferating Chlamydia-specific CD4+ T
      cells obtained from mice following resolution of a primary infection and after
      secondary challenge were assayed by an enzyme-linked immunoadsorbent assay.
      Protective CD4+ T cells restimulated in vitro secreted interleukin 2, gamma
      interferon, and interleukin 6, lymphokine profiles characteristic of both Th1-
      and Th2-like responses. Resting CD4+ T cells obtained from mice 4 months
      following resolution of a primary infection were also capable of conferring
      significant levels of adoptive protective immunity to naive mice. These findings
      support an important role for CD4+ T cells in acquired immunity to chlamydial
      infection of the genital tract and indicate that protective CD4+ immune responses
      in this model are relatively long lived.

PMID- 7642260
TI  - The C-terminal domain is essential for protective activity of the Bordetella
      pertussis adenylate cyclase-hemolysin.
AB  - The adenylate cyclase-hemolysin of Bordetella pertussis consists of a cell
      invasive N-terminal adenylate cyclase domain linked to a C-terminal RTX hemolysin
      containing extensive glycine-rich repeats. The toxin is an essential virulence
      factor required in the initial stages of infection. Adenylate cyclase-hemolysin
      was also shown to be a potent vaccinating antigen inducing protection against B.
      pertussis colonization of the mouse respiratory tract. This protective activity
      depends on a posttranslational fatty-acylation modification. We used a set of
      deletion derivatives of the recombinant adenylate cyclase-hemolysin to localize
      the protective epitopes on the 1,706-residue toxin. We show that specific anti
      adenylate cyclase-hemolysin antibodies present in the sera of B. pertussis
      infected mice and humans are directed predominantly against the modification-and
      repeat portion of the toxin, contained in the last 800 residues of the adenylate
      cyclase-hemolysin. These antibodies appear to recognize conformational epitopes
      present only in a structure formed by the intact C-terminal half of the toxin.
      There was no correlation between the capacity of the truncated adenylate cyclase
      hemolysin derivatives to induce both toxin-neutralizing antibodies upon
      immunization of mice and protective immunity. However, only the truncated
      proteins which were recognized by the sera of infected mice and humans and which
      had their last 800 residues intact had the capacity to induce protection of mice
      against colonization by B. pertussis. This indicates that the structure of the
      modification-and-repeat region of adenylate cyclase-hemolysin is critical for its
      protective activity.

PMID- 7642261
TI  - Molecular cloning and immunological characterization of a novel linear-plasmid
      encoded gene, pG, of Borrelia burgdorferi expressed only in vivo.
AB  - Previously we have found that sera from immunocompetent mice infected either
      naturally by ticks or experimentally with low numbers of Borrelia burgdorferi ZS7
      bacteria lack OspA- and OspB-specific antibodies but confer optimal protection on
      severe combined immunodeficiency mice against challenge with spirochetes (U.E.
      Schaible, L. Gern, R. Wallich, M. D. Kramer, M. Prester, and M. M. Simon,
      Immunol. Lett. 36:219-226, 1993). We have now used the latter immune sera to
      identify new spirochetal structures with relevance for protection from an
      expression library of the virulent European strain B. burgdorferi ZS7. Here we
      report the cloning and characterization of a novel lipoprotein, designated pG,
      the gene for which is located on a 48-kb linear plasmid. Sequence analysis of the
      pG gene revealed an open reading frame encoding a putative lipoprotein of 196
      amino acids with a calculated molecular mass of 22 kDa and a consensus cleavage
      sequence (Leu-X-Y-Z-Cys) recognized by signal peptidase II. Restriction fragment
      length polymorphism analyses of pG derived from independent B. burgdorferi
      isolates from different geographic areas revealed that the gene is species
      specific, with, however, extensive genotypic heterogeneity. Comparison of the
      protein sequence of pG with those of other known B. burgdorferi outer surface
      lipoproteins (OspA to OspF and P27) demonstrated that pG is most related to OspF.
      Furthermore, the upstream region of pG exhibited extensive sequence homology (>
      94%) with the ospEF promoter region. Mouse immune sera to recombinant pG did not
      recognize a corresponding molecule in lysates of in vitro-propagated ZS7
      spirochetes. However, experimental or natural infection of mice with ZS7 resulted
      in the induction of antibodies with reactivity for pG and the potential to delay
      the development of clinical arthritis. Together with the finding that sera from
      Lyme disease patients also contain antibodies to pG, our data suggest that the pG
      gene is preferentially expressed in the mammal environment.

PMID- 7642262
TI  - Variable efficacy of passive antibody administration against diverse Cryptococcus
      neoformans strains.
AB  - The efficacy of monoclonal antibody (MAb 2H1) against diverse strains of
      Cryptococcus neoformans was studied in a murine model of intravenous infection.
      For six of eight strains, administration of MAb prior to infection prolonged
      survival of mice. For two strains, 371 and SB4A, administration of MAb prior to
      infection did not prolong survival in multiple experiments with inocula ranging
      from 10(2) to 10(6) yeast cells per mouse. Mice infected with strains 371 and
      SB4A had fewer CFU than non-MAb-treated controls, but the CFU reduction was not
      sufficient to affect survival. Serum glucuronoxylomannan (GXM) levels varied for
      the different C. neoformans strains. For mice that did not receive MAb 2H1, there
      was a positive correlation between lung fungal burden and serum GXM levels. MAb
      2H1-treated mice had significantly reduced serum GXM levels. The results indicate
      that the efficacy of MAb 2H1 administration in prolonging survival and/or
      reducing organ CFU varies with the C. neoformans strain.

PMID- 7642263
TI  - Binding of host collectins to the pathogenic yeast Cryptococcus neoformans: human
      surfactant protein D acts as an agglutinin for acapsular yeast cells.
AB  - Cryptococcus neoformans is an opportunistic pathogen in AIDS patients causing
      disseminated disease and lethal meningitis after inhalation of acapsular or
      sparsely encapsulated yeast cells. In this study we have investigated whether a
      recently described family of primitive opsonins, termed collectins, contribute to
      innate resistance against C. neoformans. The pulmonary surfactant proteins SP-A
      and SP-D as well as the serum collectins mannose-binding protein and CL-43 bound
      in a calcium-dependent manner to acapsular C. neoformans in vitro. Binding was
      concentration dependent and abolished by competition with defined mono- and
      oligosaccharides. In contrast, no binding of the collectins was observed with the
      encapsulated form of the yeast. Furthermore, binding of purified collectin SP-D,
      but not SP-A, mannose-binding protein, or CL-43, led to a concentration-dependent
      agglutination of acapsular C. neoformans. These data indicate that collectins
      recognize carbohydrate structures in the cell wall of an initial infectious form
      of C. neoformans and may play a role in early antifungal defenses in the lung.

PMID- 7642264
TI  - Replacement of the DR alpha chain with the E alpha chain enhances presentation of
      Mycoplasma arthritidis superantigen by the human class II DR molecule.
AB  - Mycoplasma arthritidis mitogen (MAM) is produced by an organism which can cause
      chronic proliferative arthritis in rodents. MAM possesses a typical
      superantigenic activity; it has the ability to activate a large panel of T cells
      which express specific V beta segments of the T-cell receptor. The presentation
      of MAM to T cells by antigen-presenting cells is mediated primarily through its
      binding to the major histocompatibility complex (MHC) class II E alpha chain in
      mice and the DR alpha chain in humans. However, MAM is much less active for human
      peripheral blood lymphocytes than for mouse splenocytes. It was suggested that a
      difference in MAM binding affinity between human and mouse class II molecules may
      account for their different MAM activities. To examine this possibility, we
      generated a panel of B-cell transfectants whose DR molecule is composed of either
      the DR alpha or the E alpha chain paired with a DR3 beta chain. The ability of
      these transfectants to present MAM to human peripheral T cells was analyzed. Our
      data show that transfectants expressing E alpha DR beta chimeric molecules have
      higher MAM-presenting activity than transfectants expressing wild-type DR alpha
      DR beta molecules, while the latter have higher activity in stimulating DR3
      alloreactive T cells. Since both types of transfectants present MAM to T cells
      expressing the same T-cell receptor V beta gene families, the higher MAM
      presenting activity of the E alpha transfectant is not due to its ability to
      interact with a different set of T cells. Furthermore, both the E alpha 1 and E
      alpha 2 domains contribute to this increased affinity for MAM binding. Taken
      together, our data suggest that there may be multiple MAM binding sites on the E
      alpha and DR alpha chains and residues unique to the E alpha chain may provide
      additional affinity for MAM.

PMID- 7642265
TI  - Role of the accessory gene regulator (agr) in pathogenesis of staphylococcal
      osteomyelitis.
AB  - To examine the role of the accessory gene regulator (agr) in staphylococcal
      osteomyelitis, we compared a Staphylococcus aureus osteomyelitis isolate (UAMS-1)
      with a derivative of the same strain (UAMS-4) carrying an inactivated agr locus.
      Virulence was assessed with a rabbit model of acute, exogenous osteomyelitis.
      Bacteria were delivered by microinjection into the midradial region of the
      forelimb. After 4 weeks, UAMS-1 was identified in the bone of 12 of 13 rabbits
      infected with > or = 2 x 10(6) CFU and 5 of 6 infected with < or = 2 x 10(5) CFU.
      In contrast, UAMS-4 was found in 6 of 13 infected with the higher dose and 1 of 6
      infected with the lower dose. Additionally, on the basis of a five-point scale
      assessing radiographic evidence of disease, rabbits infected with UAMS-1 had
      average scores of 2.64 +/- 0.30 (high dose) and 1.43 +/- 0.39 (low dose) while
      rabbits infected with UAMS-4 had average scores of 0.95 +/- 0.23 (high dose) and
      0.63 +/- 0.20 (low dose). Uninfected controls had an average score of 0.53 +/-
      0.08. The results obtained with UAMS-1 were significantly different from those
      obtained with UAMS-4 at both doses (P < or = 0.047). The results obtained with
      UAMS-4 were not significantly different from those obtained with the controls at
      either dose of UAMS-4 (P > or = 0.150). On the basis of a similar five-point
      scale assessing histopathological evidence of disease, rabbits infected with UAMS
      1 had average scores of 2.31 +/- 0.22 (high dose) and 1.96 +/- 0.36 (low dose)
      while rabbits infected with UAMS-4 had average scores of 1.58 +/- 0.29 (high
      dose) and 0.83 +/- 0.32 (low dose). Controls had an average score of 0.33 +/-
      0.05. The results obtained with UAMS-1 were significantly different from those
      obtained with UAMS-4 at both doses (P < or = 0.040). However, the results
      obtained with UAMS-4 were significantly different from the controls only at the
      high dose of UAMS-4 (P = 0.025). We conclude that mutation of agr reduces the
      incidence and severity of disease but does not eliminate the ability to colonize
      bone and cause histopathological evidence of osteomyelitis.

PMID- 7642266
TI  - Susceptibility of beige mice to Mycobacterium avium: role of neutrophils.
AB  - The beige mutation in C57BL/6 mice has been shown to increase the susceptibility
      to infection by Mycobacterium avium. In this study, we confirmed those results
      and showed that the effect of the beige mutation was most obvious after infection
      with a strain of lower virulence than with a highly virulent isolate of M. avium.
      The dissemination of M. avium from the gut was observed with both C57BL/6 and
      beige mice but was faster in the latter. The expression of gamma interferon (IFN
      gamma) and the priming for tumor necrosis factor production during an in vivo
      infection were similar between beige and immunocompetent C57BL/6 mice. IFN-gamma
      produced during the infection of beige mice was protective in the spleen, and the
      administration of recombinant IFN-gamma restored the resistance in the spleen to
      levels similar to those found in control mice. There were no histological
      differences between wild-type and beige mice with respect to granuloma formation
      in the liver. The increased susceptibility of beige mice to M. avium as
      manifested in the liver was reduced by transfusing neutrophils from wild-type
      C57BL/6 mice. Likewise, depletion of neutrophils from C57BL/6 mice rendered them
      as susceptible to M. avium infection of the liver as beige mice. Our results
      point to the participation of neutrophils in the defect of beige mice in addition
      to other defects. Furthermore, these results show that neutrophils play a
      significant role in the defense mechanisms against mycobacterial infections and
      that beige animals may be a useful model for study of the role of neutrophils in
      mycobacteriosis.

PMID- 7642267
TI  - Analysis of human immunoglobulin-degrading cysteine proteinases of Trichomonas
      vaginalis.
AB  - Trichomonas vaginalis is a protozoan parasite that causes a widely distributed
      sexually transmitted disease (STD). Since immunoglobulin G (IgG) antibodies to
      specific trichomonad immunogens are found in serum and vaginal washes (VWs) from
      patients with trichomoniasis, a potential mechanism of immune evasion by this
      parasite might be the ability of T. vaginalis proteinases to degrade human
      immunoglobulins (Igs). Incubation of human IgG with lysates of T. vaginalis
      organisms resulted in time- and concentration-dependent degradation of the heavy
      chain. Secretory IgA was degraded similarly. Inhibitors of cysteine proteinases,
      when added to trichomonal lysates, abolished IgG and IgA degradation, while EDTA,
      a metalloproteinase inhibitor, did not. Substrate-gel electrophoresis with human
      IgG, IgM, or IgA copolymerized with acrylamide revealed several distinct cysteine
      proteinases in both lysates and culture supernatants from logarithmically growing
      parasites that degraded all classes of human antibodies. Trichomonal lysates and
      supernatants of numerous isolates tested all had Ig-degrading activity. Finally,
      proteolytic activity against IgG was detected in most (26 of 33; 78%) VWs from
      patients with trichomoniasis. In contrast, 18 of 28 (65%) VWs from women without
      trichomoniasis or from patients infected with other STDs had no detectable
      proteinases when tested in an identical manner. The other 10 of these 28 VWs
      (35%) had smaller amounts of detectable Ig-degrading proteinases. These
      differences in Ig-degrading proteinase activity between patients with and without
      trichomoniasis, regardless of coinfecting STDs, were statistically significant (P
      = 0.001). These results illustrate that T. vaginalis is capable of degrading
      human Igs.

PMID- 7642268
TI  - Effect of hypertriglyceridemia on endotoxin responsiveness in humans.
AB  - Triglyceride-rich lipoproteins can inhibit endotoxin activity in vitro and in
      rodents. We sought to determine whether Intralipid, a triglyceride-rich fat
      emulsion which in contact with plasma functions similarly to endogenous
      lipoproteins, can alter the human response to endotoxin. Intralipid inhibited
      endotoxin-induced cytokine production in human whole blood in vitro in a dose
      dependent manner, with maximal inhibition (up to 70%) being achieved at a
      concentration of 10 g/liter. In healthy men, a bolus intravenous injection of
      endotoxin (lot EC-5; 20 U/kg of body weight) was given midway through a 4-h
      infusion (125 ml/h) of either 5% glucose (n = 5) or 20% Intralipid (n = 5). The
      infusion of Intralipid led to an increase in triglyceride levels in serum from 95
      +/- 16 to 818 +/- 135 mg/dl prior to endotoxin administration, i.e., levels that
      importantly reduced cytokine production in endotoxin-stimulated whole blood.
      However, in vivo hypertriglyceridemia did not influence inflammatory responses to
      endotoxin (fever, release of tumor necrosis factor and soluble tumor necrosis
      factor receptors, and leukocytosis) or even potentiated endotoxin responses
      (release of interleukins 6 and 8 and neutrophil degranulation).
      Hypertriglyceridemia does not inhibit the in vivo responses to endotoxin in
      humans.

PMID- 7642269
TI  - Cytopathic effects of Treponema denticola chymotrypsin-like proteinase on
      migrating and stratified epithelial cells.
AB  - The effects of Treponema denticola and its outer membrane-bound chymotrypsin-like
      proteinase on periodontal ligament epithelial cell cultures at different stages
      of maturity were studied. In sparse cultures with migrating epithelial cells,
      large intracellular vacuoles were formed rapidly following exposure to live T.
      denticola. Treponemes showing structural damage were seen occasionally inside
      membrane-bound vesicles. Intensive membrane blebbing occurred in infected cells
      and continued for up to 48 h before the cell died. Blebbing could also be induced
      by a purified chymotrypsin-like proteinase of T. denticola. Cortical actin and
      alpha-actinin of the bacterium-treated cells showed disorganization, and
      pericellular fibronectin was degraded by both whole T. denticola and the isolated
      proteinase. Epithelial cells with well-formed lateral cell contacts appeared to
      be more resistant to the effects of T. denticola than migrating isolated cells.
      In multilayer epithelial cultures, adhesion of T. denticola and membrane blebbing
      were observed infrequently. There was no evidence of invasion of T. denticola
      into epithelial multilayers. However, immunogold electron microscopy showed rapid
      transport of T. denticola chymotrypsin-like proteinase into newly formed large
      intracellular vacuoles within the epithelial layers. These vacuoles were lined by
      membranes studded with ribosomes. T. denticola-treated epithelial multilayers had
      loose cell contacts, collapsed intercellular spaces, and increased permeability.
      Through its capacity to cause these unique cytopathic effects, the chymotrypsin
      like proteinase of T. denticola has the potential to contribute to the initiation
      of periodontal disease.

PMID- 7642270
TI  - Initial serum antibody titer to Porphyromonas gingivalis influences development
      of antibody avidity and success of therapy for chronic periodontitis.
AB  - This study assessed the effect of periodontal therapy on specific serum antibody
      concentration, expressed as titer, and antibody binding strength, expressed as
      relative avidity. The immune responses to Porphyromonas gingivalis and
      Actinobacillus actinomycetemcomitans were investigated. Antibody titer was
      assayed by enzyme-linked immunosorbent assay (ELISA) and relative avidity was
      measured by thiocyanate elution in 17 adult periodontitis patients before and
      after therapy. Immunoglobulin G (IgG) avidities (expressed as thiocyanate
      molarity) to P. gingivalis increased from 1.01 to 1.38 M (P = 0.05) and IgA
      titers (expressed as ELISA units [EU]) increased from 89 to 237 EU (P = 0.012).
      There were no significant changes in avidity to A. actinomycetemcomitans, but the
      titer of all three immunoglobulin classes increased significantly (P < 0.03).
      More specifically, when patients were divided into subgroups which had originally
      been either IgG seropositive (i.e., having an IgG titer to this organism > 2
      times the control median) or seronegative for P. gingivalis, only patients who
      were initially seropositive showed a significant increase in antibody avidity (P
      = 0.026; mean difference, 0.69 M). Patients who were originally seropositive in
      terms of IgG and IgA titer to P. gingivalis had demonstrably better treatment
      outcomes in terms of a reduced number of deep pockets and sites which bled on
      probing (P < 0.05). These findings suggest that periodontal therapy affects the
      magnitude and quality of the humoral immune response to suspected
      periodontopathogens, that this effect is dependent on initial serostatus, and
      that initial serostatus may have a bearing on treatment outcome.

PMID- 7642271
TI  - Characterization of an invasive phenotype associated with enteroaggregative
      Escherichia coli.
AB  - Enteroaggregative Escherichia coli (EAggEc) strains are associated with
      persistent diarrhea in children in the developing world and exhibit a classic
      aggregative phenotype. We have demonstrated that EAggEc strains isolated from
      children with persistent diarrhea in Brazil, Bangladesh, and Pakistan also have
      the potential to be internalized by HeLa cells in the gentamicin protection
      assay. We have confirmed this phenomenon with transmission electron micrographs
      of bacteria engulfed by HeLa cells. We examined the mechanisms by which this
      process occurs. Staurosporine inhibited internalization of EAggEc strain 162 by
      50% at a concentration of 0.1 microM. Genistein inhibited internalization of this
      same organism by 50% at a concentration of 50 microM. Cytochalasin D inhibited
      internalization by 50% at a concentration of 1 microgram/ml. Staurosporine,
      genistein, and cytochalasin D inhibited the internalization of EAggEc strain 162
      by HeLa cells in a dose-dependent manner. These data suggest that active cell
      processes such as signal transduction by protein kinase and/or tyrosine kinase
      may be involved in the internalization of EAggEc strain 162 by HeLa cells and
      that actin filaments and cytoskeletal structure may be important for this
      process.

PMID- 7642272
TI  - Deposition of complement components on Streptococcus agalactiae in bovine milk in
      the absence of inflammation.
AB  - Bovine milk is generally considered to be almost devoid of complement, on the
      basis of undetectable hemolytic activity, unless inflammation recruits plasma
      components. This study examines the deposition of complement components on a
      mastitis-causing isolate of Streptococcus agalactiae by enzyme-linked
      immunosorbent assay (ELISA). Neat milk from mid-lactating, uninflamed mammary
      glands (normal milk) effected marked C3 deposition on bacteria. Kinetic studies
      showed a protracted lag period (30 to 45 min) preceding C3 deposition, which
      required about 2 h to reach a maximum. Experiments with diluted serum suggested
      that this slow C3 deposition resulted mainly from the low concentration of
      certain components of complement in milk. Bacteria incubated in neat milk readily
      bound bovine conglutinin, indicating the presence of iC3b. Elution of covalently
      bound C3 fragments with hydroxylamine confirmed the deposition of C3b and iC3b on
      bacteria. Deposition of C4 on bacteria was not detected in neat milk, suggesting
      that C3 deposition did not result from the activation of the classical pathway.
      This was not the result of a lack of antibodies. However, C4 deposition could be
      obtained by adding purified bovine C1q to normal milk, and C3 deposition was
      accelerated, suggesting the participation of the classical pathway. The
      deposition of C1q on antibody-sensitized bacteria was impeded by milk compared
      with that of C1q diluted in phosphate-buffered saline. Concentrations of C1q in
      normal milk were very low, ranging from 150 to 250 ng/ml. Overall, these findings
      indicate that C1q was a limiting factor of the classical pathway in normal milk.
      The capacity of milk to deposit C3 fragments on mastitis-causing S. agalactiae
      prompts further studies to investigate its role in opsonophagocytosis.

PMID- 7642273
TI  - Virulence ranking of some Mycobacterium tuberculosis and Mycobacterium bovis
      strains according to their ability to multiply in the lungs, induce lung
      pathology, and cause mortality in mice.
AB  - Three virulent strains of Mycobacterium tuberculosis (H37Rv, Erdman, and NYH-27)
      and two virulent strains of M. bovis (Ravenel and Branch) were compared in terms
      of their growth rates in the livers and the lungs of mice, their ability to cause
      lung pathology, and the time taken for them to cause death. In immunocompetent
      mice, all strains caused an infection that progressed for 20 days or more and
      then underwent resolution in the liver but not in the lungs. In the lungs,
      infection persisted and induced progressive pathology. According to host survival
      time, Ravenel was the most virulent strain, followed, in decreasing order of
      virulence, by Branch, H37Rv, Erdman, and NYH-27. The much longer survival times
      of mice infected with M. tuberculosis strains allowed time for lung
      histopathology to change from a histiocytic alveolitis to a chronic fibroblastic
      fibrosis that eventually obliterated most of the lung architecture. By contrast,
      in mice infected with M. bovis strains, the alveolitis that developed during
      early infection was rapid and expansive enough to cause death before chronic lung
      pathology became evident. In mice depleted of CD4+ T cells, increased growth of
      all virulent strains induced necrotic exudative lung lesions that rapidly filled
      most of the alveolar sacs with inflammatory cells. These mice died much earlier
      than infected control mice did. Attenuated strains had longer population doubling
      times in vivo and failed to cause progressive disease or pathology in the lungs
      or livers of immunocompetent mice.

PMID- 7642274
TI  - Adhesion of Candida albicans to brain tissue of Macaca mulata in an ex vivo
      assay.
AB  - An ex vivo adhesion assay was used to examine adhesion of Candida albicans yeast
      cells to brain tissue of the primate Macaca mulata. Tissues from frontal lobes
      and striatum (caudate, putamen, and portions of the globus pallidus) were used in
      the assay. Yeast cells adhered to gray matter at about six times the level of
      adhesion to white matter. The fungus was able to bind to different cell types
      within the cortex, basal ganglia, and white matter. Binding to neurons, small
      neurons or glia, endothelial cells, and neuropil was observed.

PMID- 7642275
TI  - A Toxoplasma gondii-derived factor(s) stimulates immune downregulation: an in
      vitro model.
AB  - Suppression of the T-cell lymphoproliferative response and downregulation of
      interleukin 2 (IL-2) production by Toxoplasma gondii has been observed following
      in vivo infection. In this study, an experimental in vitro murine system was
      developed to evaluate the kinetics of these responses. Normal splenocytes from
      uninfected mice were stimulated with either concanavalin A or an anti-CD3
      monoclonal antibody and cocultured with Toxoplasma tachyzoites either directly or
      separated by a transwell. A progressive decline in the lymphoproliferative
      response was observed as the concentration of parasites in culture increased.
      Neither heat-killed nor formaldehyde-fixed parasites stimulated this
      downregulatory response by the splenocytes. A decline in IL-2 production was
      associated with the decrease in lymphocyte proliferation. The addition of an
      antibody to IL-10 or heat-inactivated anti-Toxoplasma sera to the culture
      supernatant partially neutralized the inhibitory effect on lymphocyte
      proliferation. Cytokine analysis of the responder splenocytes demonstrated a
      decrease in the message for IL-2 and IL-2 receptor and an increase in IL-10.
      Together, these observations suggest that during in vitro culture in a murine
      system, parasite antigens that stimulate the release of a soluble factor(s), such
      as IL-10, that inhibits proliferation of mitogen-stimulated T cells are
      expressed.

PMID- 7642276
TI  - Tissue localization of Cryptococcus neoformans glucuronoxylomannan in the
      presence and absence of specific antibody.
AB  - During infection, Cryptococcus neoformans capsular glucuronoxylomannan (GXM) is
      released into tissues, where it may be associated with a variety of deleterious
      immunological effects. Relatively little is known about the organ distribution
      and cellular localization of GXM antigen. Intravenous administration of GXM to
      rats resulted in persistent serum levels which declined with a half-life of 14.3
      h in the first 74 h and 3 h thereafter, coincident with the appearance of serum
      antibodies to GXM. GXM was sequestered primarily in spleen tissue, with
      localization to marginal zone and follicular cells. Administration of the murine
      immunoglobulin G1 monoclonal antibody (MAb) 2H1 resulted in > 99% reduction in
      serum GXM level within 3 h. MAb 2H1 administration resulted in liver GXM
      deposition, with cellular localization primarily to Kupffer cells. GXM was also
      found in the spleens of MAb 2H1-treated rats, with localization to the marginal
      zones and follicles. Endotracheal administration of GXM resulted in low serum
      levels, with lung tissue having the highest GXM organ levels, localized primarily
      to alveolar macrophages. The results indicate that (i) intravenous administration
      to rats produced persistent serum GXM levels with a half-life similar to that
      found in mice and rabbits; (ii) endotracheal administration of GXM resulted in
      low serum levels; (iii) in the absence of specific antibody, GXM organ deposition
      occurs primarily in the spleen and is localized primarily to marginal zone
      macrophages; (iv) in the presence of specific immunoglobulin G1 antibody, GXM
      organ deposition occurs primarily in the liver and is localized primarily to
      Kupffer cells; and (vi) reticuloendothelial cells sequester GXM in the presence
      and absence of specific antibody.

PMID- 7642277
TI  - Mycobacterial 65-kilodalton heat shock protein induces tumor necrosis factor
      alpha and interleukin 6, reactive nitrogen intermediates, and toxoplasmastatic
      activity in murine peritoneal macrophages.
AB  - The 65-kDa heat shock protein (Hsp65) is supposed to play a role in host defense
      against infections with various microbial pathogens and in autoimmune
      inflammatory disorders. These effects are thought to result mainly from an Hsp65
      specific T-lymphocyte-mediated immune response that recognizes conserved
      epitopes. The aim of the present study was to assess whether mycobacterial Hsp65
      has a direct effect on resident murine peritoneal macrophages, independent of
      Hsp65-sensitized T lymphocytes. Exposure of peritoneal macrophages from naive
      C57BL/6 mice to the mycobacterial Hsp65 in vitro induced an enhanced release of
      tumor necrosis factor alpha (TNF-alpha) and interleukin 6. These cells also
      produced large amounts of reactive nitrogen intermediates (RNI) and inhibited the
      intracellular proliferation of Toxoplasma gondii. Small amounts of gamma
      interferon acted synergistically with Hsp65. Thus, exposure of murine macrophages
      to Hsp65 results in activation of these cells. The acquisition of these
      characteristics by peritoneal macrophages occurred in the absence of sensitized T
      lymphocytes. Addition of anti-TNF-alpha antiserum resulted in an attenuation of
      the Hsp65-induced release of RNI and toxoplasmastatic activity, indicating that
      endogenous TNF-alpha is involved in the Hsp65-induced macrophage activation. The
      conclusion of this study is that in vitro exposure of peritoneal macrophages to
      the mycobacterial Hsp65 induces the release of proinflammatory cytokines and RNI
      and results in inhibition of the intracellular proliferation of T. gondii. These
      effects on murine macrophages occur independently of Hsp65-specific T
      lymphocytes. The proinflammatory effect of Hsp65 demonstrated in this study
      suggests that this heat shock protein may play a role in the initiation of
      inflammation that adds to a non-species-specific resistance in the early stages
      of infections.

PMID- 7642278
TI  - A 55-kilodalton antigen encoded by a gene on a Borrelia burgdorferi 49-kilobase
      plasmid is recognized by antibodies in sera from patients with Lyme disease.
AB  - We have identified a 55-kDa antigen encoded by a gene on a 49-kb plasmid of
      Borrelia burgdorferi. The screening of a B. burgdorferi DNA expression library
      (N40 strain) with rabbit anti-B. burgdorferi serum and then with serum from a
      patient with Lyme disease arthritis revealed a clone that synthesized an antigen
      that was reactive with both sera. DNA sequence analysis identified an operon with
      two genes, s1 and s2 (1,254 and 780 nucleotides), that expressed antigens with
      the predicted molecular masses of 55 and 29 kDa, respectively. Pulsed-field gel
      electrophoresis showed that the s1-s2 operon was located on the 49-kb plasmid.
      Recombinant S1 was synthesized as a glutathione S-transferase fusion protein in
      Escherichia coli. Antibodies to recombinant S1 bound to a 55-kDa protein in
      lysates of B. burgdorferi, indicating that cultured spirochetes synthesized S1.
      Thirty-one of 100 Lyme disease patients had immunoglobulin G (IgG) and/or IgM
      antibodies to S1. IgG antibodies to S1 were detected by enzyme-linked
      immunosorbent assay and immunoblots in the sera of 21 (21%) of 100 patients with
      Lyme disease; 11 (27.5%) of the S1-positive samples were from patients (40) with
      early-stage Lyme disease, and 10 (16.7%) were from patients (60) with late-stage
      Lyme disease. Fifteen (38.5%) of 40 serum samples from patients with early-stage
      Lyme disease had IgM antibodies to S1. These data suggest that the S1 antigen
      encoded by a gene on the 49-kb plasmid is recognized serologically by a subset of
      patients with early- or late-stage Lyme disease.

PMID- 7642279
TI  - Adherence of Borrelia burgdorferi to the proteoglycan decorin.
AB  - Lyme disease is a tick-borne infection that can develop into a chronic,
      multisystemic disorder. The causative agent, Borrelia burgdorferi, is initially
      deposited by the tick into the host dermis, where it associates with collagen
      fibers, replicates, and eventually disseminates to other tissues. We have
      examined the adherence of the spirochete to different components of the collagen
      fiber and demonstrated that decorin, a proteoglycan which decorates collagen
      fibers, can support the attachment of B. burgdorferi. No significant direct
      attachment to isolated type I or III collagens could be detected. Attachment of
      the spirochetes to decorin was highly specific, and the process could be
      inhibited by soluble decorin but not by various unlabeled, unrelated components.
      B. burgdorferi also bound soluble 125I-labeled decorin in a time- and
      concentration-dependent manner. Spirochete binding of soluble 125I-labeled
      decorin required intact proteoglycan and could not be inhibited by either
      isolated core protein or glycosaminoglycan chain. B. burgdorferi expresses two
      decorin-binding proteins with apparent molecular masses of 19 and 20 kDa as
      revealed in a Western blot (immunoblot)-type assay. Our results indicate that
      decorin may mediate the adherence of B. burgdorferi to collagen fibers in skin
      and other tissues.

PMID- 7642280
TI  - Identification of a possible cytadherence regulatory locus in Mycoplasma
      pneumoniae.
AB  - Transposon mutagenesis was used to analyze Mycoplasma pneumoniae cytadherence.
      Mycoplasmas were electroporated with Tn4001, and transformants were identified by
      antibiotic selection using gentamicin. The resulting colonies were screened for
      hemadsorption (HA) as an indicator for cytadherence. Six HA- colonies from
      independent transformations were isolated, filter cloned, and characterized in
      more detail. Southern hybridization analysis revealed that all six transposon
      insertions mapped to the same 252-kbp ApaI fragment and 19.5-kbp XhoI fragment.
      More detailed analysis localized the insertion to two adjacent EcoRI fragments.
      This site is distinct from the locus containing the genes for the high-molecular
      weight cytadherence-accessory proteins HMW1 and HMW3, and yet these proteins were
      absent from the protein profiles of all six transformants. To determine if
      transposon insertion was responsible for the HA- phenotype, reversion frequencies
      of the transformants were assessed after passage in the presence of antibiotic
      selection. In contrast to a spontaneously arising HMW-deficient variant, which
      reverted to an HA+ phenotype readily, no HA+ revertants were identified for any
      of the six transformants. These observations suggest that a potential regulatory
      locus that may be important in the expression of the HMW cytadherence-accessory
      proteins has been identified.

PMID- 7642281
TI  - Intracellular multiplication and toxic destruction of cultured macrophages by
      Capnocytophaga canimorsus.
AB  - Capnocytophaga canimorsus is a gram-negative rod that causes opportunistic
      infections resulting in bacteremia, septicemia, meningitis, and death in
      immunocompromised, splenectomized, and alcoholic individuals. Infections caused
      by a related species, Capnocytophaga cynodegmi, remain localized at the site of
      the wound where the organism is introduced. Both organisms are part of the normal
      canine oral flora and are introduced through puncture wounds via dog bites. We
      found that both C. canimorsus and C. cynodegmi attach, are phagocytized, and
      multiply intracellularly in J774 mouse macrophage cells. After 48 h of infection
      by C. canimorsus, large sections of the macrophage cell layer were observed to
      detach and lyse, while the monolayer infected with C. cynodegmi demonstrated no
      cytotoxic effects. Tissue culture supernatants from the C. canimorsus-infected
      J774 cells filtered through a 0.22-micron-pore membrane produced a similar effect
      on fresh monolayers, while filtrates from C. cynodegmi and uninfected controls
      produced no effect. No endotoxin release was observed in these supernatants. We
      conclude that the cytotoxic phenotype of C. canimorsus is the likely result of a
      toxin produced by this organism.

PMID- 7642282
TI  - Binding of human plasminogen to Borrelia burgdorferi.
AB  - We studied the binding of plasminogen to Borrelia burgdorferi, a spirochete which
      causes Lyme disease and produces no endogenous proteases which digest
      extracellular matrix proteins. Using 125I-labeled plasminogen, we demonstrated
      that B. burgdorferi bound human plasminogen and that this binding was inhibitable
      with unlabeled plasminogen. 125I-labeled plasminogen binding by B. burgdorferi
      was also inhibited by the lysine analog epsilon-aminocaproic acid. There was no
      significant difference in the binding of Glu- or Lys-plasminogen to B.
      burgdorferi. Binding of plasminogen was similar in low-passage (infectious) and
      high-passage (noninfectious) isolates of B. burgdorferi. Plasminogen bound to the
      surface of B. burgdorferi could be converted into plasmin by a human urokinase
      type plasminogen activator. 125I-labeled plasminogen ligand blots of borrelial
      membrane proteins demonstrated two prominent binding proteins at approximately 70
      and approximately 30 kDa. By Western blot (immunoblot), the 30-kDa protein was
      found to be outer surface protein A (Osp A) of B. burgdorferi. 125I-labeled
      plasminogen binding to both the 70-kDa protein and Osp A was inhibited by
      approximately 90% with a 1,000-fold excess of unlabeled plasminogen. By scanning
      densitometry, the 70-kDa band bound > 10 time more 125I-labeled plasminogen than
      did Osp A. An Osp A-deficient mutant of B. burgdorferi and wild-type B.
      burgdorferi bound equal amounts of 125I-labeled plasminogen. Ligand blots of
      membrane proteins from an Osp A-deficient mutant showed association of 125I
      labeled plasminogen at only the 70-kDa protein. Two-dimensional gel
      electrophoresis showed that the 70-kDa protein had a pI of approximately 5.3,
      clearly separable from Osp A. The association of host plasmin(ogen) with
      borrelial surface proteins provides a mechanism by which B. burgdorferi can
      digest extracellular matrix and disseminate.

PMID- 7642283
TI  - Rapid and sensitive method for evaluating Pseudomonas aeruginosa virulence
      factors during corneal infections in mice.
AB  - A murine corneal scratch model has been used extensively to study various aspects
      of the pathogenesis of Pseudomonas aeruginosa, a common etiologic agent of
      corneal infections. This model uses mild inhalation anesthetics which keep the
      animals immobile for a relatively short time and promote the interaction between
      the infecting organisms and the corneal wound. Under these circumstances, only a
      small number of P. aeruginosa isolates delivered at inocula of > 10(7) CFU are
      infectious. We determined that this model is useful for studying other P.
      aeruginosa strains given at lower doses if injectable anesthetics are
      administered prior to infection to keep the animals immobile for 15 to 30 min.
      Under these conditions, eight clinical isolates of P. aeruginosa tested at doses
      of 10(8) CFU per eye induced corneal perforation and/or phthisis in C3H/HeN mice.
      The 50% infective doses of several strains were between 3 x 10(2) and 1 x 10(5)
      CFU per mouse eye. When this modified anesthetic procedure was used to evaluate
      the roles of different P. aeruginosa virulence factors in eye infections,
      pathology was not observed when eyes were inoculated with 10(8) CFU of strains
      deficient in production of a complete lipopolysaccharide or the RpoN sigma
      factor. A strain with a point mutation in the fur gene, involved in production of
      iron-regulated factors, showed decreased virulence, while a mutant deficient in
      both hemolytic and nonhemolytic phospholipase C was fully virulent. By modifying
      the anesthesia procedure, the corneal scratch model allows rapid evaluations of
      the roles of P. aeruginosa virulence factors in corneal infections.

PMID- 7642284
TI  - Entry and survival of Leishmania amazonensis amastigotes within phagolysosome
      like vacuoles that shelter Coxiella burnetii in Chinese hamster ovary cells.
AB  - Coxiella burnetii, a rickettsia, and Leishmania amazonensis, a protozoan
      flagellate, lodge in their host cells within large phagolysosome-like vacuoles.
      In the present study, C. burnetii-infected Vero or CHO cells were superinfected
      with L. amazonensis amastigotes to determine if these parasites can home to and
      survive within heterologous vacuoles. Six hours after superinfection, Leishmania
      amastigotes were located almost exclusively within large Coxiella-containing
      vacuoles. Thereafter, the numbers of parasites in the vacuoles increased at the
      same rate as those in cells infected with L. amazonensis alone. Furthermore, in
      cultures shifted to 25 degrees C, some of the amastigotes transformed into
      promastigote-like forms that moved their flagella within the adoptive vacuoles.
      Thus, L. amazonensis amastigotes not only entered Coxiella vacuoles, most likely
      by fusion of donor and recipient vacuoles, but temporarily survived,
      differentiated, and replicated therein. This appears to be the first account of
      the temporary cohabitation of two living pathogens within the same vacuole in a
      mammalian cell.

PMID- 7642285
TI  - Roles of gamma interferon and interleukin-4 in genetically determined resistance
      to Coccidioides immitis.
AB  - The profiles of gamma interferon (IFN-gamma) and interleukin-4 (IL-4) production
      were evaluated during the course of coccidioidomycosis in two inbred mouse
      strains which differ in their susceptibility to Coccidioides immitis. Cytokine
      responses, measured at the molecular and protein levels, showed increased levels
      of IFN-gamma in lung extracts from mice of the resistant DBA/2 strain after a
      pulmonary challenge, whereas the susceptible BALB/c strain manifested a
      predominant IL-4 response. The importance of these cytokines in host defense
      against C. immitis was established by treating the mice with recombinant
      cytokines or neutralizing anticytokine monoclonal antibodies. Treatment of the
      susceptible BALB/c mice with recombinant murine IFN-gamma significantly protected
      mice against systemic challenge, and in the reciprocal experiment, the
      administration of an anti-IFN-gamma monoclonal antibody to the resistant DBA/2
      mice significantly decreased their capacity to control disease. Although the
      treatment of DBA/2 mice with recombinant IL-4 did not alter the disease,
      neutralization of endogenous IL-4 in infected BALB/c mice by administration of a
      neutralizing anti-IL-4 antibody led to a significant reduction in the fungal load
      in their tissues. These results, taken together, establish that IFN-gamma plays a
      pivotal role in resistance to C. immitis, whereas IL-4 down-regulates protective
      immunity against C. immitis.

PMID- 7642286
TI  - Sulfated polyanions block Chlamydia trachomatis infection of cervix-derived human
      epithelia.
AB  - Using a cell line derived from the human cervix and a rapid fluorescence
      cytotoxicity assay, we have shown that Chlamydia trachomatis infection can be
      blocked by certain sulfated polysaccharides (carrageenan, pentosan polysulfate,
      fucoidan, and dextran sulfate) and glycosaminoglycans (heparin, heparan sulfate,
      and dermatan sulfate) but not by other glycosaminoglycans (chondroitin sulfate A
      or C, keratan sulfate, and hyaluronic acid). The most negatively charged
      molecules are the most effective at blocking infection. Results of infection at 4
      degrees C suggest that sulfated polyanions act by preventing the adherence of
      chlamydiae to target cells. These and additional blocking studies with enzymes
      suggest that a heparan sulfate-like glycosaminoglycan on the surface of
      elementary bodies is involved in the adherence of chlamydiae to target cells,
      probably through a nonspecific charge interaction or possibly a heparin-binding
      protein. We previously observed that the same sulfated polysaccharides inhibit
      transmission of human immunodeficiency virus in vitro and suggested that these
      compounds could be used in a vaginal formulation to inhibit infection by human
      immunodeficiency virus. The results of the present study suggest that the same
      type of formulation may inhibit sexual transmission of chlamydia.

PMID- 7642287
TI  - Murine cytotoxic T lymphocytes induced following Chlamydia trachomatis
      intraperitoneal or genital tract infection respond to cells infected with
      multiple serovars.
AB  - The obligate intracellular bacterium Chlamydia trachomatis is associated with
      human diseases ranging from blinding trachoma to sexually acquired genital
      infections and the systemic disease lymphogranuloma venereum (LGV). We have
      previously reported the isolation and culture of protective murine cytotoxic T
      lymphocytes (CTL) following intraperitoneal infection with C. trachomatis serovar
      L2, a serotype associated with human LGV. In this report, we now demonstrate that
      CTL can also be primed following introduction of C. trachomatis serovar L2 into
      the uterus or ovarian bursa of mice. We also describe Chlamydia-specific CTL
      lines isolated following murine infection with a typical human urogenital isolate
      of C. trachomatis (serovar D) and show that such CTL can be primed by
      intraperitoneal, intrauterine, or intrabursal infection. Last, we demonstrate
      that these murine CTL lines respond to multiple serovars, recognizing and lysing
      cells infected with C. trachomatis serovars B, C, D, F, J, K, L2, and L3,
      representative of organisms causing blinding trachoma, genital infection, and
      LGV.

PMID- 7642288
TI  - Comparison among opsonic activity, antimeningococcal immunoglobulin G response,
      and serum bactericidal activity against meningococci in sera from vaccinees after
      immunization with a serogroup B outer membrane vesicle vaccine.
AB  - Opsonic activity in sera from 27 military recruits vaccinated with the Norwegian
      meningococcal serogroup B outer membrane vesicle vaccine was measured as
      respiratory burst with polymorphonuclear leukocytes as the effector cells and
      meningococci of the epidemic strain as the target. The results were compared with
      antimeningococcal IgG antibodies against an outer membrane vesicle coat in an
      enzyme-linked immunosorbent assay and with serum bactericidal activity. The
      vaccinees were immunized twice, with a 6-week interval between the two. The serum
      samples studied were collected at day zero, after 6 weeks, and after 12 weeks.
      Both serum bactericidal activity and respiratory burst were measured by adding
      external serum as the complement source. The results revealed a significant
      increase in specific IgG response, serum bactericidal activity, and respiratory
      burst after vaccination. We found a highly significant correlation between the
      responses in all three assays (P < 0.0001). The highest correlation was found
      between respiratory burst and antimeningococcal IgG response (r = 0.93). This
      result strongly indicates that respiratory burst is mediated almost exclusively
      by IgG antibodies. The correlation between antimeningococcal IgG response and
      serum bactericidal activity was slightly lower (r = 0.83). The correlation
      between respiratory burst and serum bactericidal activity was further reduced (r
      = 0.78), and some of the sera revealed a marked preference for only one of the
      activities. This result means that respiratory burst and serum bactericidal
      activity in part are induced by different mediators, and to obtain a more
      complete picture of the potential protective activity, both assays should be
      applied to survey a vaccine trial.

PMID- 7642291
TI  - Role of the 145-kilodalton surface protein in virulence of the Brazilian purpuric
      fever clone of Haemophilus influenzae biogroup aegyptius for infant rats.
AB  - Brazilian purpuric fever (BPF) is a fulminant infection associated with
      bacteremia with clonally related strains of Haemophilus influenzae biogroup
      aegyptius. Case-associated clone strains are more virulent for infant rats than
      are non-BPF case-associated H. influenzae biogroup aegyptius isolates. I sought
      to determine the possible role of P145, a 145-kDa surface protein of BPF case H.
      influenzae biogroup aegyptius clone isolates, in virulence. First, I compared the
      virulence of two case-associated clone isolates from the blood of children with
      BPF from Serrana, Brazil, which differed in P145 expression but were identical in
      all other phenotypic and genotypic characteristics studied. Twenty-four hours
      after intraperitoneal inoculation of infant rats, there was a significantly
      higher incidence (51 versus 26%; P = 0.035) and magnitude (2.9 +/- 5.8 versus 0.7
      +/- 2.0 CFU/0.01 ml; P = 0.024) of bacteremia in rats inoculated with the P145
      expressing strain. I next compared the virulence of a P145-expressing case
      associated clone strain with two P145-nonexpressing phase variants of this
      strain. One variant exhibited a lower mean magnitude of bacteremia and one
      displayed a similar magnitude of bacteremia compared with that displayed the P145
      expressing parental strain. P145-expressing revertants of the P145-nonexpressing
      strains exhibited the same virulence as the P145-negative variants from which
      they were derived. Colonies grown from blood cultures maintained the P145
      phenotype of the inoculated strain. These results suggest that P145 expression
      does not contribute to the virulence of the BPF case clone strain for infant rats
      following intraperitoneal inoculation.

PMID- 7642290
TI  - Mechanisms of inhibition of Cryptococcus neoformans by human lymphocytes.
AB  - Recently, our laboratory and others have demonstrated that human peripheral blood
      T and NK lymphocytes directly inhibit the growth of Cryptococcus neoformans. In
      this study, we further define the conditions under which lymphocyte-mediated
      fungistasis against C. neoformans occurs and examine whether mechanisms
      implicated in lymphocyte-mediated activities against other target cells are also
      involved in anticryptococcal activity. The addition of whole or broken heat
      killed C. neoformans modestly inhibited lymphocyte-mediated fungistasis, whereas
      other particulates had no effect. The hydroxyl radical scavenger catechin, but
      not diethyl urea or propyl gallate, profoundly inhibited fungistasis. Salicylic
      acid inhibited fungistasis in a dose-dependent fashion. However, two other
      cyclooxygenase inhibitors, piroxicam and indomethacin, had no effect, suggesting
      that the mechanism of inhibition by salicylic acid was cyclooxygenase
      independent. Reagent prostaglandin E2, at concentrations shown by others to
      inhibit NK cell-mediated bactericidal and tumorlytic activities, had no effect on
      lymphocyte-mediated fungistasis. The addition of selected monoclonal antibodies
      or ligands reactive with receptors on human lymphocytes had no significant effect
      on lymphocyte-mediated fungistasis. Acapsular, small-capsuled, and large-capsuled
      C. neoformans organisms were inhibited by lymphocytes to an approximately equal
      extent. These data demonstrate that lymphocyte-mediated activity against C.
      neoformans proceeds regardless of the presence of capsule and by mechanisms at
      least in part dissimilar from those seen with other target cells.

PMID- 7642289
TI  - Recombinant OspA protects dogs against infection and disease caused by Borrelia
      burgdorferi.
AB  - Twenty-two specific-pathogen-free beagles were vaccinated with recombinant OspA
      (ospA gene derived from Borrelia burgdorferi B31) alone or with adjuvant (QuilA,
      Montanide ISA25, or aluminum hydroxide) at 6 weeks of age. Thirteen dogs were
      used as nonvaccinated controls with or without adjuvant. Three dogs were kept as
      contact controls and received neither vaccine nor challenge. Six weeks or 6
      months after the first vaccination, the vaccinated (20 of 22) and nonvaccinated
      dogs (13) were challenged by exposure to adult ticks (Ixodes scapularis)
      naturally that were infected with B. burgdorferi (tick infection rate, > or =
      60%) and that were collected from Westchester County, N.Y. Protection from
      infection was evaluated by culture for B. burgdorferi from skin biopsies taken
      near the sites of tick bites. Skin biopsies were taken at monthly intervals for 3
      months. B. burgdorferi was not isolated from any of the vaccinated dogs. In
      contrast, 12 of 13 control dogs challenged by exposure to the ticks were culture
      positive. The histopathology of the joint capsules 3 months after the challenge
      was used to evaluate protection from arthritis. Eight of 13 control dogs showed
      synovitis in single or multiple joints, while only 1 of the 22 vaccinated dogs
      had a single focus of mild inflammation in a single joint. At the time of the
      challenge, the vaccinated dogs had antibody to B. burgdorferi, which was
      demonstrable by kinetic enzyme-linked immunosorbent assay, Western blotting
      (immunoblotting), and a serum growth inhibition assay. The vaccinal antibody
      declined gradually after the challenge, especially in dogs vaccinated with OspA
      without adjuvants. Antibodies in the challenge control dogs were only detectable
      by 4 to 6 weeks after the challenge and remained at high levels until the
      termination of the study. Contact control dogs showed no antibody responses or
      histopathologic lesions and were culture negative. By Western blot analysis,
      antibodies to OspA first appeared in the sera of vaccinated dogs 3 weeks after
      the first vaccination. The absence of additional bands after the challenge
      suggests that infection in vaccinated dogs was blocked. Results from this study
      show that vaccination with recombinant OspA protected dogs against infection and
      disease after an experimental challenge with B. burgdorferi by exposure to ticks.

PMID- 7642292
TI  - Leishmania pifanoi amastigote antigens protect mice against cutaneous
      leishmaniasis.
AB  - In the search for a leishmaniasis vaccine, extensive studies have been carried
      out with promastigote (insect stage) molecules. Information in this regard on
      amastigote (mammalian host stage) molecules is limited. To investigate host
      immune responses to Leishmania amastigote antigens, we purified three stage
      specific antigens (A2, P4, and P8) from in vitro-cultivated amastigotes of
      Leishmania pifanoi by using immunoaffinity chromatography. We found that with
      Corynebacterium parvum as an adjuvant, three intraperitoneal injections of 5
      micrograms of P4 or P8 antigen provided partial to complete protection of BALB/c
      mice challenged with 10(5) to 10(7) L. pifanoi promastigotes. These immunized
      mice developed significantly smaller or no lesions and exhibited a 39- to 1.6 x
      10(5)-fold reduction of lesion parasite burden after 15 to 20 weeks of infection.
      In addition, P8 immunization resulted in complete protection against L.
      amazonensis infection of CBA/J mice and partial protection of BALB/c mice,
      suggesting that this antigen provided cross-species protection of mice with
      different H-2 haplotypes. At different stages during infection, vaccinated mice
      exhibited profound proliferative responses to parasite antigens and increased
      levels of gamma interferon production, suggesting that a Th1 cell-mediated immune
      response is associated with the resistance in these mice. Taken together, the
      data in this report indicate the vaccine potential of amastigote-derived
      antigens.

PMID- 7642293
TI  - Inflammatory cytokine gene expression in human periodontal ligament fibroblasts
      stimulated with bacterial lipopolysaccharides.
AB  - The effects of Porphyromonas gingivalis lipopolysaccharide (P-LPS) and
      Escherichia coli lipopolysaccharide (E-LPS) on the gene expression and production
      of inflammatory cytokines of human periodontal ligament fibroblasts (HPLF) were
      examined by a Northern (RNA blot) assay and enzyme-linked immunosorbent assay,
      respectively. mRNAs for interleukin-6 (IL-6), IL-8, and transforming growth
      factor beta (TGF-beta) were detected in HPLF cells, but IL-1 alpha, IL-1 beta,
      tumor necrosis factor alpha, transforming growth factor alpha, and granulocyte
      macrophage colony-stimulating factor were not detected by reverse transcription
      PCR. The expression of TGF-beta mRNA was not influenced by either LPS. P-LPS (1
      to 10 micrograms/ml) and E-LPS (100 micrograms/ml) markedly stimulated the
      expression of IL-6 and IL-8 mRNAs compared with the control. The synthesis of IL
      6 and IL-8 was also stimulated by 10 and 100 micrograms of both LPSs per ml, but
      IL-8 synthesis was not stimulated with E-LPS at 1 microgram/ml. Secretion of IL-6
      and IL-8 into the culture medium was detected at 6 and 3 h, respectively, after
      exposure to P-LPS (10 micrograms/ml). These findings suggested that P. gingivalis
      leads to periodontal tissue destruction and alveolar bone resorption through IL-6
      and IL-8 released from HPLF cells stimulated with its LPS.

PMID- 7642294
TI  - Enteral human serum immunoglobulin treatment of cryptosporidiosis in mice with
      severe combined immunodeficiency.
AB  - The anti-cryptosporidial immunoglobulin G antibodies in two commercially
      available human serum immunoglobulin (HSIG) products were quantified and
      characterized. The mean level of Cryptosporidium parvum-specific immunoglobulin G
      in HSIG was eightfold higher than the antibody level found in the sera of three
      immunocompetent individuals convalescing from cryptosporidiosis. However, HSIG
      products displayed no reactivity to cryptosporidial antigens in immunoblot
      analyses, while convalescent-phase sera demonstrated characteristic banding
      patterns. When HSIG was given to newborn severe combined immunodeficiency (scid)
      mice before and shortly after experimental infection, a decreased intensity of
      infection was observed in the intestines of the mice compared with that of
      control mice. However, there was no difference in mortality or histopathologic
      findings in the intestines of HSIG-treated and control mice when treatment was
      not started until 22 days of age. These results indicate that HSIG may be
      beneficial when given prophylactically; however, HSIG cannot eradicate
      cryptosporidia from mucosal surfaces in an established infection.

PMID- 7642295
TI  - Inflammatory cytokine expression in swine experimentally infected with
      Actinobacillus pleuropneumoniae.
AB  - An Actinobacillus pleuropneumoniae infection model in swine was established to
      study the expression of inflammatory cytokines during acute respiratory disease.
      Lavage fluid, lavage cells consisting primarily of alveolar macrophages, and lung
      tissue were analyzed for the presence of various cytokines at 2, 4, 8, and 24 h
      following endotracheal inoculation of A. pleuropneumoniae. Interleukin-1 beta (IL
      1) and IL-8 mRNA levels were elevated within 2 h in lavage cells of animals
      inoculated with A. pleuropneumonia but not in cells from controls treated with
      saline-bovine serum albumin, based on Northern (RNA blot) analysis. Tumor
      necrosis factor (TNF) mRNA was present at low levels in all animals, and the
      level was not increased at any time point. In situ hybridization was more
      sensitive than Northern blotting and revealed elevations of all three cytokines
      in lavage cells within 2 to 4 h of A. pleuropneumoniae inoculation. IL-6 was
      detected in lavage cells by in situ hybridization but not by Northern blotting.
      In lung tissue obtained 18 to 24 h after A. pleuropneumoniae instillation, all
      cytokine mRNAs, including that of IL-6, were detected by Northern blot analysis.
      The levels of bioactive IL-1 and IL-6 in lavage fluids increased approximately
      1,000-fold following A. pleuropneumoniae inoculation, but TNF bioactivity was not
      detected. Morphological localization of cytokine mRNAs by in situ hybridization
      indicated markedly increased levels of TNF, IL-1, and IL-8 mRNAs at the periphery
      of focal lung lesions. These findings indicate that inflammatory cytokines,
      particularly IL-1 and IL-8, are associated with the development of
      pleuropneumonia and may contribute to disease severity.

PMID- 7642296
TI  - Pasteurella haemolytica lipopolysaccharide-associated protein induces pulmonary
      inflammation after bronchoscopic deposition in calves and sheep.
AB  - The lipopolysaccharide (LPS)-associated protein (LAP) was extracted from
      Pasteurella haemolytica serotype A1 strains L101 (bovine origin) and 82-25 (ovine
      origin). Extracts contained 0.017% total LPS and appeared as only two bands at 14
      and 16.6 kDa after sodium dodecyl sulfate-polyacrylamide gel electrophoresis. To
      determine the extent of pulmonary inflammation induced by LAP and its possible
      role in the pathogenesis of pneumonic pasteurellosis, LAP (500 micrograms in
      pyrogen-free saline [PFS]) was deposited by fiber-optic bronchoscopy into the
      dorsum of the caudal portion of the cranial lobe of the right lung of calves
      (strain L101 LAP) and sheep (strain 82-25 LAP). LPS (500 micrograms in PFS), 3-h
      P. haemolytica cultures (1.6 x 10(8) to 1.9 x 10(8) CFU in PFS), and PFS alone
      were deposited similarly as controls. At necropsy, 24 h after deposition, gross
      and histologic pulmonary lesions of calves and sheep given LAP, LPS, and P.
      haemolytica were similar and consisted of various degrees of acute
      bronchopneumonia (relative severities of lesions induced: LAP < LPS < live
      organisms). By subjective histologic interpretation and semiquantitative
      morphometry, animals given LAP had the highest percentage of macrophages per
      alveolar lumen and the lowest percentage of neutrophils. The lesions from animals
      given LPS were more severe than those given LAP, but the morphometric cell counts
      were similar. In contrast, animals inoculated with P. haemolytica had lesions
      typical of this agent, consisting of many neutrophils, proteinaceous exudate, and
      a few macrophages. Morphometrically, these lesions had the highest numbers of
      neutrophils and the lowest numbers of macrophages. These studies show that LAP
      can induce an inflammatory response in the alveolar lumens and may play a role in
      the pathogenesis of pneumonic pasteurellosis.

PMID- 7642297
TI  - Interaction of outer envelope proteins of Chlamydia psittaci GPIC with the HeLa
      cell surface.
AB  - The chlamydial life cycle involves the intimate interaction of components of the
      infectious elementary body (EB) surface with receptors on the susceptible
      eukaryotic cell plasma membrane. We have developed an in vitro ligand binding
      assay system for the identification and characterization of detergent-extracted
      EB envelope proteins capable of binding to glutaraldehyde-fixed HeLa cell
      surfaces. With this assay, the developmentally regulated cysteine-rich envelope
      protein Omp2 of Chlamydia psittaci strain guinea pig inclusion conjunctivitis was
      shown to bind specifically to HeLa cells. HeLa cells bound Omp2 selectively over
      other cell wall-associated proteins, including the major outer membrane protein,
      and the binding of Omp2 was abolished under conditions which alter its
      conformation. Furthermore, trypsin treatment, which reduces EB adherence,
      resulted in the proteolytic removal of a small terminal peptide of Omp2 at the EB
      surface and inactivated Omp2 in the ligand binding assay, while having a
      negligible effect on the major outer membrane protein. Collectively, our results
      suggest that Omp2 possesses the capacity to engage in a specific interaction with
      the host eukaryotic cell. We speculate that, since Omp2 is present only in the
      infectious EB form, the observed in vitro interaction may be representative of a
      determining step of the chlamydial pathogenic process.

PMID- 7642298
TI  - Association of Legionella pneumophila with the macrophage endoplasmic reticulum.
AB  - Legionella pneumophila replicates within a membrane-bounded compartment that is
      studded with ribosomes. In this study we investigated whether these ribosomes
      originate from the cytoplasmic pool or are associated with host endoplasmic
      reticulum (ER). Immunofluorescence and electron microscopic localization studies
      of ER proteins in macrophages infected with L. pneumophila indicated that the
      bacteria reside in a compartment surrounded by ER. An L. pneumophila mutant that
      grows slowly in macrophages was slow to associate with host ER, providing genetic
      evidence in support of the hypothesis that this specialized vacuole is required
      for intracellular bacterial growth. Ultrastructural studies, in which the ER
      luminal protein BiP was labeled by immunoperoxidase cytochemistry, revealed that
      L. pneumophila replication vacuoles resemble nascent autophagosomes. Furthermore,
      short-term amino acid starvation of macrophages, which stimulated host
      autophagosomes. Furthermore, short-term amino acid starvation of macrophages,
      which stimulated host autophagy, increased association of the bacteria with the
      ER and enhanced bacterial growth. These results are compatible with the
      hypothesis that L. pneumophila exploits the autophagy machinery of macrophages to
      establish an intracellular niche favorable for replication.

PMID- 7642299
TI  - The role of the eaeA gene in diarrhea and neurological complications in a
      gnotobiotic piglet model of enterohemorrhagic Escherichia coli infection.
AB  - We reported previously that mutation of the chromosomal gene eaeA from
      enterohemorrhagic Escherichia coli (EHEC) serotype O157:H7 prevented bacterial
      attachment in vivo. Attachment was restored when the EHEC or enteropathogenic E.
      coli (EPEC) eaeA gene was introduced into the mutant on a plasmid. In this
      communication we have compared in gnotobiotic piglets the pathogenicities of wild
      type O157:H7 strain 86-24 and its eaeA mutant UMD619 with those of the two
      plasmid-complemented strains expressing IntiminO157 (EHEC) and IntiminO127
      (EPEC). 86-24 colonized the surface and glandular epithelium of the large
      intestine and induced diarrhea, while UMD619 did not colonize any intestinal site
      and induced little or no diarrhea. Surprisingly, strain UMD619 expressing
      IntiminO127 behaved in pigs more like EPEC than EHEC strains; it colonized the
      distal half of the small intestine and the surface of the large intestine,
      inducing serious diarrhea. In contrast, strain UMD619 expressing IntiminO157
      colonized the colon extremely poorly, inducing little or no diarrhea. While only
      the two strains causing extensive attachment--86-24 and UMD619 expressing
      IntiminO127--induced diarrhea, neurological symptoms attributed to Shiga-like
      toxin II occurred equally in all four groups of animals. The intimate bacterial
      attachment and mucosal damage were not a prerequisite for Shiga-like toxin II
      translocation from the gut lumen into the circulation. IntiminO127 appears not
      only to facilitate intimate attachment to cells but also to influence the site of
      intestinal colonization and other characteristics of EPEC infection.

PMID- 7642300
TI  - Platelet receptors for the Streptococcus sanguis adhesin and aggregation
      associated antigens are distinguished by anti-idiotypical monoclonal antibodies.
AB  - Platelets aggregate in response to an adhesin and the platelet aggregation
      associated protein (PAAP) expressed on the cell surfaces of certain strains of
      Streptococcus sanguis. We sought to identify the corresponding PAAP receptor and
      accessory adhesin binding sites on platelets. Since the adhesion(s) of S. sanguis
      for platelets has not been characterized, an anti-idiotype (anti-id) murine
      monoclonal antibody (MAb2) strategy was developed. First, MAb1s that
      distinguished the adhesin and PAAP antigens on the surface of S. sanguis I 133-79
      were selected. Fab fragments of MAb1.2 (immunoglobulin G2b [IgG2b]; 70 pmol)
      reacted with 5 x 10(7) cells of S. sanguis to completely inhibit the aggregation
      of human platelets in plasma. Under similar conditions, MAb1.1 (IgG1) inhibited
      the adhesion of S. sanguis cells to platelets by a maximum of 34%, with a
      comparatively small effect on platelet aggregation. Together, these two MAb1s
      inhibited S. sanguis-platelet adhesion by 63%. In Western immunoblots, both MAb1s
      reacted with S. sanguis 133-79 87- and 150-kDa surface proteins and MAb1.2 also
      reacted with purified type I collagen. The hybridomas producing MAb1.1 and MAb1.2
      were then injected into BALB/c mice. Enlarged spleens were harvested, and a panel
      of MAb2 hybridomas was prepared. To identify anti-ids against the specific MAb1s,
      the MAb2 panel was screened by enzyme-linked immunosorbent assay for reaction
      with rabbit polyclonal IgG antibodies against the 87- and 150-kDa antigens. The
      reactions between the specific rabbit antibodies and anti-ids were inhibited by
      the 87- and 150-kDa antigens. When preincubated with platelets, MAb2.1
      (counterpart of MAb1.1) inhibited adhesion to platelets maximally by 46% and
      MAb2.2 (anti-MAb1.2) inhibited adhesion to platelets maximally by 35%. Together,
      both MAb2s inhibited the adhesion of S. sanguis to platelets by 81%. MAb2.2 also
      inhibited induction of platelet aggregation. MAb2.2 immunoprecipitated a
      biotinylated platelet membrane antigen of 170 kDa (unreduced); MAb2.1
      precipitated membrane antigens of 175- and 230-kDa (unreduced). Therefore,
      platelet binding sites and the receptor for the S. sanguis adhesin and PAAP,
      respectively, are distinguished by the anti-id MAb2s.

PMID- 7642301
TI  - Staphylococcus aureus induces platelet aggregation via a fibrinogen-dependent
      mechanism which is independent of principal platelet glycoprotein IIb/IIIa
      fibrinogen-binding domains.
AB  - Platelet aggregation by bacteria is felt to play an important role in the
      pathogenesis of infective endocarditis. However, the mechanisms involved in
      bacterium-induced platelet aggregation are not well-defined. In the present
      study, we examined the mechanisms by which Staphylococcus aureus causes rabbit
      platelet aggregation in vitro. In normal plasma, the kinetics of S. aureus
      induced platelet aggregation were rapid and biphasic. The onset and magnitude of
      aggregation phase 1 varied with the bacterium-platelet ratio, with maximal
      aggregation observed at a ratio of 5:1. The onset of aggregation phase 2 was
      delayed in the presence of apyrase (an ADP hydrolase), suggesting that this later
      aggregation phase may be triggered by secreted ADP. The onset of aggregation
      phase 2 was delayed in the presence of prostaglandin I2-treated platelets, and
      this phase was absent when paraformaldehyde-fixed platelets were used,
      implicating platelet activation in this process. Platelet aggregation phase 2 was
      dependent on S. aureus viability and an intact bacterial cell wall, and it was
      mitigated by antibody directed against staphylococcal clumping factor (a
      fibrinogen-binding protein) and by the cyclooxygenase inhibitor indomethacin.
      Similarly, aggregation phase 2 was either delayed or absent in three distinct
      transposon-induced S. aureus mutants with reduced capacities to bind fibrinogen
      in vitro. In addition, a synthetic pentadecapeptide, corresponding to the
      staphylococcal binding domain in the C terminus of the fibrinogen delta-chain,
      blocked aggregation phase 2. However, phase 2 of aggregation was not inhibited by
      two synthetic peptides (alone or in combination) analogous to the two principal
      fibrinogen-binding domains on the platelet glycoprotein (GP) IIb/IIIa integrin
      receptor: (i) a recognition site on the IIIa molecule for the Arg-Gly-Asp (RGD)
      sequence of the fibrinogen alpha-chain and (ii) a recognition site on the IIb
      molecule for a dodecapeptide sequence of the fibrinogen delta-chain. This differs
      from ADP-induced platelet aggregation, which relies on an intact platelet GP
      IIb/IIIa receptor with an accessible RGD sequence and dodecapeptide recognition
      site for fibrinogen. Furthermore, a monoclonal antibody directed against the RGD
      recognition site on rabbit platelet GP IIb/IIIa receptors failed to inhibit
      rabbit platelet aggregation by S. aureus. Collectively, these data suggest that
      S. aureus-induced platelet aggregation requires bacterial binding to fibrinogen
      but is not principally dependent upon the two major fibrinogen-binding domains on
      the platelet GP IIb/IIIa integrin receptor, the RGD and dodecapeptide recognition
      sites.

PMID- 7642302
TI  - Increased protein secretion and adherence to HeLa cells by Shigella spp.
      following growth in the presence of bile salts.
AB  - Growth of Shigella spp. in the presence of the bile salt deoxycholate or
      chenodeoxycholate enhanced the bacterial invasion of HeLa cells. Growth in the
      presence of other structurally similar bile salts or detergents had little or no
      effect. Deoxycholate-enhanced invasion was not observed when bacteria were
      exposed to deoxycholate at low temperatures or when chloramphenicol was added to
      the growth medium, indicating that bacterial growth and protein synthesis are
      required. Increased invasion is associated with the presence of an intact
      Shigella virulence plasmid and is correlated with increased secretion of a set of
      proteins, including the Ipa proteins, to the outer membrane and into the growth
      medium. The increased invasion induced by the bile salts appears to be due to
      increased adherence. The enhanced adherence was specific to Shigella spp., since
      the enteroinvasive Escherichia coli strains tested did not exhibit the effect in
      response to growth in bile salts.

PMID- 7642303
TI  - T-cell, adhesion, and B-cell epitopes of the cell surface Streptococcus mutans
      protein antigen I/II.
AB  - The T-cell and antibody responses to a cell surface streptococcal antigen (SA
      I/II) were investigated in naturally sensitized humans. Serum antibody responses
      were directed predominantly to the N-terminal (residues 39 to 481) and central
      (residues 816 to 1213) regions of SA I/II which may be involved in bacterial
      adhesion to salivary receptors. T-cell responses were also directed predominantly
      towards the central region. The linear peptide relationship of the immunodominant
      and minor T- and B-cell as well as adhesion epitopes was mapped within residues
      816 to 1213. Immunodominant T-cell and B-cell epitopes were identified within
      residues 803 to 853, which were separated in linear sequence from the adhesion
      epitopes (residues 1005 to 1044). Adhesion epitopes overlapped with minor B- and
      T-cell epitopes (residues 1005 to 1054 and 1085 to 1134). An immunodominant
      promiscuous T-cell epitope (residues 985 to 1004) was adjacent to an adhesion
      epitope (residues 1005 to 1024). The limited B-cell response to adhesion epitopes
      is consistent with the success of Streptococcus mutans in colonizing the oral
      cavity. The strategy of T-cell, adhesion, and B-cell epitope mapping has revealed
      a general approach for identifying components of subunit vaccines which may focus
      responses to critical functional determinants. Such epitopes of SA I/II may
      constitute the components of a subunit vaccine against dental caries.

PMID- 7642304
TI  - Bacterial plasminogen receptors: in vitro evidence for a role in degradation of
      the mammalian extracellular matrix.
AB  - The potential of bacterium-bound plasmin to degrade mammalian extracellular
      matrix and to enhance bacterial penetration through basement membrane was
      assessed with the adherent strain SH401-1 of Salmonella enterica serovar
      Typhimurium. Typhimurium SH401-1 was able to bind plasminogen and to enhance the
      tissue-type plasminogen activator-mediated activation of the single-chain
      plasminogen to the two-chain plasmin. The end product, the enzymatically active,
      bacterium-bound plasmin activity, was also formed in a normal human plasma milieu
      in the presence of exogenous tissue-type plasminogen activator, indicating that
      plasmin was protected from the plasminogen activator inhibitors and plasmin
      inhibitors of plasma. Plasmin bound on Typhimurium cells degraded 125I-labeled
      laminin as well as 3H-labeled extracellular matrix prepared from the human
      endothelial cell line EA.hy926. The degradations were not seen with Typhimurium
      cells without plasminogen and were inhibited by the low-molecular-weight plasmin
      inhibitor aprotinin. Plasmin bound on Typhimurium cells also potentiated
      penetration of bacterial cells through the basement membrane preparation Matrigel
      reconstituted on membrane filters. The results give in vitro evidence for
      degradation of the mammalian extracellular matrix by bacterium-bound plasmin and
      for a pathogenetic role for bacterial plasminogen receptors.

PMID- 7642306
TI  - Effect of anti-tumor necrosis factor alpha antibodies on histopathology of
      primary Salmonella infections.
AB  - We reported that administration of anti-tumor necrosis factor alpha (anti-TNF
      alpha) antibodies exacerbates the course of a Salmonella infection in both
      susceptible and resistant mice by preventing the suppression of bacterial growth
      in the reticuloendothelial system. In the present study, we evaluated the effect
      of in vivo neutralization of TNF-alpha on the histopathology of primary
      Salmonella infections. We show that in primary infections, the suppression of
      bacterial growth in the reticuloendothelial system coincides with granuloma
      formation in the spleen and liver. Administration of anti-TNF-alpha globulins on
      day -1 of salmonellosis affected neither the histological picture nor the course
      of the infection in the early stages of the disease (days 1 to 3), with splenic
      and hepatic lesions consisting mainly of polymorphonuclear leukocytes (PMNs);
      conversely, later in infection (days 3 to 7), the treatment inhibited the
      formation of granulomas. When the anti-TNF-alpha treatment was started well after
      the suppression of bacterial growth in the reticuloendothelial system and the
      formation of granulomatous lesions in the spleen and liver, a prompt relapse of
      the infection and regression of already established granulomas were seen. In anti
      TNF-alpha-treated mice, salmonellae were found inside macrophages and PMNs and
      extracellularly in the necrotic tissue of the spleen, while in the liver the
      organisms were seen mainly in inflammatory mononuclear cells, resident Kupffer
      cells, and hepatocytes and occasionally in the extracellular compartment within
      necrotic lesions. The bacteria appeared most often in clusters, being
      morphologically intact when in the extracellular space or within hepatocytes,
      while undergoing various degrees of degeneration when inside phagocytes. The
      results suggest that TNF-alpha is required for granuloma formation in
      salmonellosis and that its neutralization does not completely abrogate the
      bactericidal activity of macrophages and PMNs. Salmonellae were observed to grow
      within both hepatocytes and phagocytes but were killed only in the latter.

PMID- 7642305
TI  - Interaction of Listeria monocytogenes with mouse dendritic cells.
AB  - In this study, the interaction of murine dendritic cells with Listeria
      monocytogenes was investigated. Dendritic cells are efficient antigen-presenting
      cells, play a key role in the immune response, and are capable of migrating over
      substantial distances between sites of infection and lymphoid tissues. L.
      monocytogenes EGD invaded dendritic cells, escaped from phagosomes into the
      cytoplasm, and there directed actin nucleation, polymerization, and polarization
      in a typical fashion, thereby achieving intracellular movement and cell-to-cell
      spread. The internalization process appears to be independent of the inl locus.
      Interestingly, an intact microtubular function was essential for efficient
      uptake, whereas in a previous report, microtubule disruption did not affect
      bacterial spread in Caco-2 cells. The results obtained also suggest that L.
      monocytogenes binds to glycosylated receptors of dendritic cells. Uptake of
      Listeria cells was mediated by a protein kinase-dependent transducing
      phosphorylation signal that induces the actin polymerization-dependent phagocytic
      process. To achieve efficient uptake, de novo protein synthesis of eukaryotic and
      prokaryotic cells is also required. Despite the killing of dendritic cells, wild
      type bacteria were found to persist in small numbers in some cells for at least
      24 h. When different isogenic mutants of the EGD strain were analyzed for their
      capability to interact with dendritic cells, it was observed that some virulence
      attenuated mutants (i.e., prfA and delta hly) persisted in large numbers for even
      longer times. Invasion of dendritic cells by L. monocytogenes, which in turn
      could result in either cell death or persistent infection, might have an
      important role in the pathogenesis of listeriosis, leading to impaired immune
      responses with inefficient bacterial clearance and/or promoting bacterial spread.

PMID- 7642307
TI  - Purification and characterization of Eikenella corrodens type IV pilin.
AB  - Eikenella corrodens is a gram-negative human pathogen associated with periodontal
      diseases and soft-tissue infections. Pilin was purified by association
      dissociation and fast protein liquid chromatography; it had an apparent molecular
      mass of about 14.8 kDa and an N-terminal amino acid sequence reflective of type
      IV pilins. Antibodies to the purified protein reacted with pili on whole cells.
      This is the first report of purification of type IV pili/pilin from this
      organism. Other type IV pili are important virulence factors; we are currently
      investigating the biological role of pili in E. corrodens.

PMID- 7642308
TI  - Decomplementation by cobra venom factor suppresses Yersinia-induced arthritis in
      rats.
AB  - Lewis rats experimentally infected with Yersinia enterocolitica O8 develop
      Yersinia-induced arthritis (YIA), which resembles very much reactive arthritis in
      humans. To investigate the involvement of serum complement in induction and
      maintenance of YIA, we decomplementated Yersinia-infected Lewis rats by treatment
      with cobra venom factor starting on day 7 after infection (prearthritic state).
      Reduction of serum complement activity in vivo by cobra venom factor treatment
      coincided with suppression of YIA clinically and histomorphologically.

PMID- 7642309
TI  - Murine complement reduces infectivity of Plasmodium yoelii to mosquitoes.
AB  - The alternative pathway of complement in the mouse serum significantly reduced,
      but did not eliminate, the infectivity of Plasmodium yoelii to Anopheles
      stephensi. The reduction of the infectivity is mainly due to the inability of the
      zygote to transform into the ookinete in the mosquito midgut.

PMID- 7642310
TI  - Pathogenicity of human and porcine intestinal spirochetes in one-day-old specific
      pathogen-free chicks: an animal model of intestinal spirochetosis.
AB  - One-day-old chicks were infected orally with two strains of weakly hemolytic
      spirochetes isolated from a human and a pig with intestinal spirochetosis. These
      spirochetosis both colonized birds, attached end-on to their cecal enterocytes,
      induced watery diarrhea, and significantly depressed growth rates. Cultures of
      Serpulina innocens failed to colonize the chicks.

PMID- 7642311
TI  - Cytotoxic effects of natural killer cells have no significant role in controlling
      infection with the intracellular protozoon Eimeria vermiformis.
AB  - The course of infection with Eimeria vermiformis in C57BL/6J; NK cell-defective
      C57BL/6J bg/bg; BALB/c; T-cell-defective BALB/c nu/nu; and T-cell-, B-cell-, and
      NK cell-defective BALB/c x C57BL/6 scid/scid bg/bg mice was monitored. For young
      C57BL/6J mice, the bg/bg mutants consistently produced fewer oocysts than the
      controls; there were no differences between older mice of these strains. Wild
      type BALB/c mice were more resistant to infection than the nu/nu and scid/scid
      bg/bg mutants, but there was no difference between the mutants. Treatment of
      BALB/c mice with poly(I.C) had no effect on the course of infection. These
      findings confirm the ineffectiveness of NK cells in this system.

PMID- 7642312
TI  - Tumor necrosis factor alpha acts as an autocrine second signal with gamma
      interferon to induce nitric oxide in group B streptococcus-treated macrophages.
AB  - Nitric oxide production by mouse macrophages treated with group B streptococci
      and gamma interferon was inhibited by cytochalasin B or by antibody
      neutralization of macrophage-derived tumor necrosis factor alpha. Phagocytosis
      induced tumor necrosis factor alpha is responsible for group B streptococcus
      induced nitric oxide production in interferon-treated macrophages.

PMID- 7642313
TI  - Construction and characterization of an isogenic urease-negative mutant of
      Helicobacter mustelae.
AB  - Helicobacter mustelae infects the ferret stomach and provides an opportunity to
      study pathogenic determinants of a Helicobacter species in its natural host. We
      constructed an isogenic urease-negative mutant of H. mustelae which produced no
      detectable urease and showed a reduced acid tolerance. This mutant provides an
      opportunity to further evaluate the role of urease in the pathogenesis of
      Helicobacter infection.

PMID- 7642314
TI  - Inability of an isogenic urease-negative mutant stain of Helicobacter mustelae to
      colonize the ferret stomach.
AB  - Eight ferrets specific-pathogen-free for Helicobacter mustelae were given, per
      dose, approximately 3.0 x 10(7) CFU of either the wild-type parent strain of H.
      mustelae (NCTC 12032) (two ferrets) the isogenic urease-negative mutant strain of
      H. mustelae (10::Tn3Km) (four ferrets), or sterile culture broth (two ferrets).
      Infection status was monitored by endoscopic gastric biopsy for urease activity,
      histopathology, and culture and by serology at 3, 6, 10, and 21 weeks. All
      ferrets were necropsied at 25 weeks. Both negative control ferrets remained
      uninfected, both ferrets receiving the H. mustelae wild-type parent strain became
      infected after two doses of the organism, and all four ferrets given two doses of
      the isogenic urease-negative mutant strain of H. mustelae remained uninfected
      throughout the 6-month study. Histopathology correlated with infection status. H.
      mustelae-infected ferrets exhibited diffuse mononuclear inflammation in the
      subglandular region and the lamina propria of the gastric mucosa, while
      uninfected ferrets showed no or minimal inflammation. These results suggest that
      urease activity is essential for colonization of the ferret stomach by H.
      mustelae.

PMID- 7642315
TI  - Immunogenicity in Peruvian volunteers of a booster dose of oral cholera vaccine
      consisting of whole cells plus recombinant B subunit.
AB  - Forty-nine subjects received two doses of oral cholera vaccine consisting of
      whole cells plus recombinant B subunit; this was followed by a booster dose one
      year later. After the primary series, a significant (greater than twofold)
      increase in the levels of vibriocidal, anti-cholera toxin immunoglobulin G and
      anti-cholera toxin immunoglobulin A antibodies occurred in 54, 88, and 81% of the
      subjects, respectively. Within one year, titers decreased to levels close to
      baseline. A booster dose then induced rises to those which occurred after the
      initial vaccination. The results suggest that 1-year booster doses may be
      necessary to maintain immunity against cholera in Latin America.

PMID- 7642316
TI  - Spontaneous change from overt to covert infection of Chlamydia pecorum in
      cycloheximide-treated mouse McCoy cells.
AB  - Some isolates of Chlamydia pecorum from sheep feces failed to produce inclusions
      on passage in cycloheximide-treated monolayers, but chlamydiae could be recovered
      several weeks later. Chlamydia psittaci from sheep abortions did not show this
      phenomenon.

PMID- 7642317
TI  - Immunogenicity and protective efficacy of a prototype Campylobacter killed whole
      cell vaccine in mice.
AB  - The immunogenicity and efficacy of an experimental inactivated Campylobacter
      jejuni whole-cell (CWC) vaccine were evaluated in mice. Mice were orally
      immunized in a three-dose primary series (48-h intervals) at doses of 10(5),
      10(7), or 10(9) CWC vaccine particles alone or in combination with 25 micrograms
      of a mucosal adjuvant, the heat-labile enterotoxin of Escherichia coli (LT). The
      comparative immunogenicities of both formulations were assessed on the basis of
      the generation of antigen-specific antibodies in serum and intestinal secretions,
      and efficacy was determined by measuring the degrees of protection afforded
      against intestinal colonization and systemic dissemination of challenge
      organisms. Campylobacter-specific intestinal immunoglobulin (Ig) A responses were
      dependent on the use of LT, whereas IgA and IgG responses in serum were not.
      Colonization resistance was induced over a broad range of vaccine doses when LT
      was included. However, only the highest dose of CWC alone gave comparable levels
      of protection. Both formulations provided equivalent protection against systemic
      spread of challenge organisms. These results indicate that both whole-cell
      vaccine formulations deserve further evaluation as candidate vaccines and also
      highlight the potential value of mucosal adjuvants, like LT, in enteric vaccine
      development.

PMID- 7642318
TI  - Mice deficient in gamma delta T cells are resistant to lethal infection with
      Salmonella choleraesuis.

PMID- 7642319
TI  - Enterohemorrhagic Escherichia coli O157:H7 requires intimin to colonize the
      gnotobiotic pig intestine and to adhere to HEp-2 cells.
AB  - In a previous study, enterohemorrhagic Escherichia coli (EHEC) O157:H7 with a
      deletion and insertion in the eaeA gene encoding intimin was used to establish
      that intimin is required for the organism to attach to and efface microvilli in
      the piglet intestine (M. S. Donnenberg, S. Tzipori, M. L. McKee, A. D. O'Brien,
      J. Alroy, and J. B. Kaper, J. Clin. Invest. 92:1418-1424, 1993). However, in the
      same investigation, a role for intimin in EHEC adherence to HEp-2 cells could not
      be definitively demonstrated. To analyze the basis for this discrepancy, we
      constructed an in-frame deletion of eaeA and compared the adherence capacity of
      this mutant with that of the wild-type strain in vitro and in vivo. We observed a
      direct correlation between the requisite for intimin in EHEC O157:H7 colonization
      of the gnotobiotic piglet intestine and adherence of the bacterium to HEp-2
      cells. The in vitro-in vivo correlation lends credence to the use of the HEp-2
      cell adherence model for further study of the intimin protein.

PMID- 7642320
TI  - Is asialo GM1 present in rabbit and human corneal epithelium?

PMID- 7642321
TI  - Molecular cloning, characterization, and expression in Escherichia coli of iron
      superoxide dismutase cDNA from Leishmania donovani chagasi.

PMID- 7642322
TI  - A new non-instrumental technique for cleaning and filling root canals.
AB  - The aim of this in vitro study was to test the ability of a novel non
      instrumental technique to prepare and obturate root canals. Cleaning of the root
      canal system was achieved with a device which was able to develop, under reduced
      pressure, controlled cavitation. The same device was used for proper drying and
      subsequent obturation of the root canal system. A total of 55 freshly extracted
      molars with 120 canals were treated either by the step-back technique and lateral
      condensation of gutta-percha and AH26 as a sealer or by the new device. The teeth
      were then sectioned horizontal to the long axis of the root canal and examined by
      light microscopy. The cross-sectional area, area with residual pulpal tissue and
      voids were assessed morphometrically. Overall, the treatment with the new device
      resulted in similar cleanliness and obturation quality when compared with the
      control group. Total treatment time using the new non-instrumental technique,
      however, was less than half of that using hand instrumentation.

PMID- 7642323
TI  - Periapical status of endodontically treated teeth in relation to the technical
      quality of the root filling and the coronal restoration.
AB  - The purpose of this study was to evaluate the relationship of the quality of the
      coronal restoration and of the root canal obturation on the radiographic
      periapical status of endodontically treated teeth. Full-mouth radiographs from
      randomly selected new patient folders at Temple University Dental School were
      examined. The first 1010 endodontically treated teeth restored with a permanent
      restoration were evaluated independently by two examiners. Post and core type
      restorations were excluded. According to a predetermined radiographic standard
      set of criteria, the technical quality of the root filling of each tooth was
      scored as either good (GE) or poor (PE), and the quality of the coronal
      restoration similarly good (GR) or poor (PR). The apical one-third of the root
      and surrounding structures were then evaluated radiographically and the
      periradicular status categorized as (a) absence of periradicular inflammation
      (API) or (b) presence of periradicular inflammation (PPI). The rate of API for
      all endodontically treated teeth was 61.07%. GR resulted in significantly more
      API cases than GE, 80% versus 75.7%. PR resulted in significantly more PPI cases
      than PE, 30.2% versus 48.6%. The combination of GR and GE had the highest API
      rate of 91.4%, significantly higher than PR and PE with a API rate of 18.1%.

PMID- 7642324
TI  - Localization of chondroitin sulphate and dermatan sulphate in human dental pulps-
      an immunohistochemical study.
AB  - The distribution of dermatan sulphate and chondroitin sulphate in human dental
      pulps has been assessed using monoclonal antibodies and immunoperoxidase
      localization techniques. The pulpal tissues were reacted with specific antibodies
      following pretreatment of the sections with chondroitinase ACII or chondroitinase
      ABC. Both the 4- and 6-sulphates isomers of chondroitin sulphate were detected in
      the tissues studied. Very little dermatan sulphate could be detected. These
      glycosaminoglycans appeared throughout the pulpal connective tissues with a
      particularly strong localization to the region adjacent to the odontoblastic and
      predentine layers. Such distribution strongly implicates chondroitin sulphate in
      the mineralization process of human dentine.

PMID- 7642325
TI  - Comparison of radiovisiography with radiographic film in root length
      determination.
AB  - Radiovisiography is a digital intraoral radiographic imaging system requiring a
      substantial reduction of radiation dosage to the patient over film. For
      Radiovisiography to replace film, it must be shown to be as efficacious. In this
      study, a technique of obtaining Radiovisiography and D-speed film images from the
      same X-ray beam was developed with the use of rare-earth filters. The quality of
      the resultant radiovisiographic images was verified in vitro with pure
      radiovisiographic images of teeth in a dried mandible with soft tissue
      simulation. Two examiners compared Radiovisiography with D-speed film for 20 root
      length estimations using the same in-vitro model. A clinical study was then
      carried out on mandibular molars of patients undergoing endodontic treatment,
      where 35 root lengths were obtained. The results of both in vitro and clinical
      studies showed no statistical differences in the estimated root lengths using the
      two imaging systems. The measuring grid available in the Radiovisiography unit
      produced similarly accurate results. Furthermore, the clinical study demonstrated
      the effective use of Radiovisiography during root canal treatment, with instant
      images.

PMID- 7642326
TI  - A comparison of the apical dye penetration patterns shown by methylene blue and
      india ink in root-filled teeth.
AB  - This study compared the linear leakage patterns shown by 5% aqueous solution of
      methylene blue (MB) and India ink (II). One-hundred and twenty-five roots with
      single canals from extracted human teeth were used. The canals were cleaned and
      shaped using the step-back technique under copious irrigation. Three groups were
      arranged to receive root fillings of gutta-percha and one of three proprietary
      sealers using standard lateral condensation techniques: Sealapex (40 roots),
      Tubli-Seal (40 roots) and Ketac-Endo (20 roots). The remaining roots were used as
      controls: positive with gutta-percha and no sealer and negative with the apices
      sealed with nail varnish. The roots were randomly selected for 7-day immersion in
      either MB or II, then sectioned longitudinally; dye penetration was assessed
      using a Wild Leitz stereomicroscope. In all groups MB showed more penetration
      than II. The results were statistically significant at the P = 0.01 level, with
      the exception of the positive control groups. Negative controls showed no
      penetration. It is concluded that MB, which has a low molecular weight penetrated
      more deeply along root canal fillings than II, which has a large particle size.

PMID- 7642327
TI  - Sealability of the Trifecta technique in the presence or absence of a smear
      layer.
AB  - The aim of this in vitro study was to assess the sealability of a recently
      introduced thermoplasticized gutta-percha technique (Trifecta, Hygenic Corp., OH,
      USA) in the presence or absence of a smear layer. A total of 100 teeth with
      single straight root canals were included in the study. The teeth were
      decoronated and the canals prepared with a modified double-flared technique under
      constant irrigation with 2.5% sodium hypochlorite solution. The apical matrix was
      prepared to size 40 and apical patency subsequently confirmed with a size 10
      file. Four teeth were discarded for technical reasons and the remaining 96
      allocated randomly into two groups of 44 teeth and a group of eight teeth which
      acted as controls. Canals in group 1 were obturated randomly with either cold
      lateral condensation of gutta-percha or with the Trifecta technique. Canals in
      Group 2 were rinsed with 17% REDTA to remove the smear layer and then obturated
      with lateral condensation or the Trifecta technique. All teeth were suspended in
      India ink for 9 days, demineralized, and rendered transparent prior to the
      assessment of apical linear dye penetration. Apical extrusion of sealer and gutta
      percha occurred commonly but there was no significant difference between the four
      obturation groups. However, overall, there was significantly more extrusion of
      sealer with the Trifecta technique compared with lateral condensation (P < 0.05).
      The majority of canals (79 out of 88) had no evidence of apical leakage and there
      was no significant difference between the groups.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7642328
TI  - The guided tissue regeneration principle in endodontic surgery: one-year
      postoperative results of large periapical lesions.
AB  - Twenty patients with large endodontic lesions, which failed to respond to
      conventional endodontic therapy, were selected for this study. The lesions had a
      radiographic diameter of at least 10 mm, were removed by periradicular surgery,
      before retrofilling the apices with either super EBA or dessicated zinc oxide
      eugenol. In 10 test sites large e-PTFE membranes (Gortex) were placed to cover
      the lesions, while at the control sites the lesions were not covered before
      resuturing. Radio-graphic analysis of the lesions at 3, 6, 9 and 12 months
      revealed that lesions covered with the membranes healed quicker than the control
      lesions, and that the quality and quantity of the regenerated bone was superior
      when membranes were used. Results of the study indicate that guided tissue
      regeneration (GTR) principles can be effectively applied to the healing of large
      periapical lesions, especially in through-and-through lesions.

PMID- 7642329
TI  - Factors affecting the clinical efficiency of ultrasonic endodontics: a scanning
      electron microscopy study.
AB  - The purpose of this pilot study was to investigate some of the clinical variables
      in ultrasonic endodontics. forty extracted human teeth with a single, straight
      root 21-25 mm in length were prepared using combinations of the following
      variables: hand or ultrasonic instrumentation; apical seat prepared to file sizes
      35, 40, 45 or 50; 1 ml of water, 4% sodium hypochlorite or EDTAC as irrigant
      between each instrument size; three brands of ultrasound generator and inserts; a
      'low', 'medium' or 'high' effective power output; a tuned or untuned circuit;
      post-instrumentation ultrasonic irrigation with either 4% sodium hypochlorite,
      EDTAC, or the two used in sequence. The specimens were viewed in a scanning
      electron microscope and scored for the presence or absence of a smear layer at
      levels < 1 mm, 5 mm and 10 mm from the apical seat. The most effective
      combination, as tested, was hand instrumentation to file size 40 with 1 ml EDTAC
      irrigation between each instrument size, supplemented by intermittent flush
      irrigation with EDTAC with ultrasound then 4% sodium hypochlorite with
      ultrasound. This technique left a minimum smear layer restricted to the apical
      seat. Other combinations of instrumentation and irrigation were not consistent in
      their effectiveness.

PMID- 7642330
TI  - The influence of ultrasound in removing intraradicular posts.
AB  - Thirty single-rooted teeth were prepared to receive cast posts. After cementation
      of the post the teeth were divided into three groups. Group I did not receive any
      treatment, whereas the posts in groups II and III were treated with an ultrasonic
      device, for 2 min and 5 min, respectively. The force required for post removal
      was determined using a universal test machine. No statistical differences (P >
      0.05) were found between the groups where ultrasound had been used. Significantly
      reduced forces were necessary to remove the posts from group II and III, compared
      with group I which did not receive ultrasonic treatment (P < 0.05).

PMID- 7642331
TI  - Evaluation of long-term calcium hydroxide treatment in avulsed teeth--an in vivo
      study.
AB  - Calcium hydroxide has been advocated for use in avulsed teeth as a temporary
      dressing in an attempt to prevent or inhibit external resorption. However, there
      have been no long-term histological studies that have examined gutta-percha
      versus calcium hydroxide treatment in avulsed teeth. The purpose of this study
      was to determine the long-term therapeutic effect of calcium hydroxide therapy in
      avulsed teeth. Six adult macaca monkeys were anesthetized and all four maxillary
      incisors were extracted and bench-dried for 25 min. The teeth were replanted and
      splinted with composite for approximately 2 weeks. Each animal served as its own
      control and the teeth were accessed, instrumented, and filled with either Ca(OH)2
      or gutta-percha and AH26 cement. All access openings were filled with composite.
      The Ca(OH)2 was replaced twice during the experimental period (approximately
      every 8 weeks). The animals were killed between 5 and 7.5 months post-avulsion.
      The teeth were removed, sectioned, and examined histologically by two examiners.
      The results of the histological evaluation of external resorption indicated that
      there were no statistically significant differences in resorption indices between
      the teeth obturated with gutta percha or with calcium hydroxide (P > 0.05).
      Replacement resorption was the primary cause of root destruction and only a few
      histological sections exhibited evidence of inflammatory resorption.

PMID- 7642332
TI  - Immunohistochemistry of anterior proliferative vitreoretinopathy. Report of 11
      cases.
AB  - Anterior proliferative vitreoretinopathy is characterized by epiretinal
      proliferation that extends anteriorly over the vitreous base, and may, in
      addition to the cells usually contributing to proliferative vitreoretinopathy,
      also contain cells of ocular structures located in that area. We examined 11
      complete globes with aPVR that were enucleated after previous severe trauma or
      perforating injuries (n = 8) and complicated retinal detachment (n = 3) by a
      panel of immunohistochemical markers. We found presence of RPE, glial cells,
      macrophages and fibrocytes, as consistently reported in PVR membranes. In
      addition, T-cell lymphocytes were present in 6 of the cases, and cells expressing
      the common leucocyte antigen on 8 cases. Cells staining positive for the
      intracytoplasmic contractile filament alpha-smooth muscle actin were present in 5
      cases and cells staining for desmin in one case. Collagen type IV was part of
      most of the membranes, and vessels with leakage of plasma factors were present in
      more than half of the cases.

PMID- 7642333
TI  - Immunohistochemistry of cellular proliferation in eyes with longstanding retinal
      detachment.
AB  - To further characterize the content and nature of cyclitic membranes (n = 4),
      ringschwielen (n = 3) and a subretinal strand on sections of complete globes with
      long-standing retinal detachment after trauma (n = 7) or retinal reattachment
      surgery (n = 1), we applied a panel of cellular and extracellular antibodies
      using the APAAP (alkaline phosphatase and monoclonal anti-alkaline phosphatase)
      technique. Only one cyclitic membrane from an eye that was enucleated two months
      after trauma was positive for glial fibrillary acidic protein, demonstrating the
      presence of glial cells. All cyclitic membranes contained macrophages and
      expressed intracellular contractile proteins. Ringschwielen stained consistently
      for cells of epithelial origin (RPE) with cytokeratin and for macrophages. The
      subretinal strand stained for cytokeratin, macrophages and alpha-smooth muscle
      actin, supporting cellular contraction in the genesis of this form of
      proliferative vitreoretinopathy.

PMID- 7642334
TI  - Changes of color vision in ocular hypertension.
AB  - Fifty-six ocular hypertension (OHT) patients were examined for 2-3 days in the
      Eye Clinic of Kuopio University Hospital. No glaucomatous changes were found.
      Twenty-seven of them were found to have several risk factors for developing
      glaucoma and medication was started. Twenty-nine of the patients did not show
      risk factors and had no medication. Color vision was examined with the Farnsworth
      Munsell 100 (FM 100) hue test and Besancon anomalometer, later Color Vision Meter
      712 at the beginning of the study and 3 years later. None of the 56 patients
      showed any glaucomatous changes after 3 years of the study. In the treatment
      group, the FM 100 test showed significantly (paired t-test, p = 0.004) improved
      error scores after 3 years. In the non-treatment group, 19 patients did not
      develop risk factors; they had no significant changes in the color vision
      results. In 10 patients of the non-treatment group, risk factors had developed
      with elevated intraocular pressure and medication was started for them after 3
      years. Their color vision results in the blue anomalous quotient (AQ) of the
      anomalometer had significantly shifted to the blue part of the equation (paired t
      test, p = 0.04). The other color vision results had not changed significantly.
      The significantly improved FM 100 scores in the treatment group could mean, that
      the treatment has a beneficial effect for the OHT eyes at risk for developing
      glaucoma.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7642336
TI  - Full-thickness macular holes treated with vitrectomy and tissue glue.
AB  - In the surgical treatment of full-thickness macular holes good results have been
      published with the combination of vitrectomy, gas and application of Transforming
      Growth Factor beta 2. Other authors report a 73% success rate in closing a full
      thickness macular hole after vitrectomy and gas tamponade alone. We used, in
      addition to vitrectomy and gas tamponade, a tissue glue to stimulate adhesion of
      the elevated cuff of neurosensory retina surrounding a full-thickness macular
      hole and to close to hole itself. A total of 15 eyes of 13 patients (3 men, 10
      women), with stage 3 and 4 macular holes were operated. All of the 13
      uncomplicated cases showed complete closure of the macular hole. In one case (8%)
      the visual acuity decreased one line in spite of a funduscopically closed hole,
      and in two cases (16%) visual acuity remained the same despite closure. Increased
      visual acuity was seen in ten cases (76%), eight of which improved more than two
      lines.

PMID- 7642337
TI  - Retinal complications after bungee jumping.
AB  - Bungee jumping is becoming a popular sport in the Western world with some cases
      of ophthalmic complications being reported in recent literature. The authors
      reported a case of a 23-year-old healthy female who presented retinal
      complications following a bungee jumping. Her fundi showed superficial retinal
      hemorrhages in the right eye and a sub-internal limiting membrane hemorrhage
      affecting the left eye. A general examination, including a full neurological
      examination, was normal and laboratorial investigations were all within normal
      values. More studies are necessary to identify risk factors and the true
      incidence of related ocular lesions, but until then, we think this sport activity
      should be desencouraged, especially to those that are not psychological and
      physically fit.

PMID- 7642335
TI  - Topical treatment of postvitrectomy fibrin formation with tissue plasminogen
      activator.
AB  - Tissue plasminogen activator (tPA) is able to dissolve any fibrin material that
      forms in the anterior chamber or vitreous humor. This property has been reported
      by various experimental studies performed in rabbits. The authors demonstrate the
      tPA eye drops administered to patients with postoperative hyphema, which did not
      respond to traditional therapy, gave rapid clearance of the clot. Following its
      topical administration for the first time in patients, the harmless nature of the
      drug is emphasized as well as its efficacy. This study indicates the promising
      features of this drug which deserve further investigation.

PMID- 7642339
TI  - Casteldaccia eye study: prevalence of cataract in the adult and elderly
      population of a Mediterranean town.
AB  - Prevalence of cataract was studied in a population based survey performed in
      adults aged 40 years or more living in Casteldaccia, a small Sicilian town. Lens
      opacities of moderate or severe grade (type II or worse, according to the Lens
      Opacity Classification System II) were found at the following rates: nuclear
      opalescence in 18.5%, cortical cataract in 12.9%, posterior subcapsular cataract
      in 10.8%. All these types of cataract were much more frequent in the elderly
      population and were about 1.5 times more common in women than in men. Late
      cataract was found in about 1/3 of subjects aged 60 to 69 years, in 2/3 of
      subjects aged 70 or more, but rarely under 60 years of age. However, early
      cataract was rather common among younger subjects. Cataracts causing a reduction
      of visual acuity under 0.7 in the worst eye were found in 4%, 8.7% and 21.5%
      respectively in the three age groups ranging from 40 to 49, 50 to 59 and 60 to 69
      years and in 54.4% of subjects 70 years old or over.

PMID- 7642338
TI  - Wegener's granulomatosis, pituitary adenoma and BARN.
AB  - A 53-year-old man with Wegener's granulomatosis and a co-existing pituitary
      adenoma developed bilateral acute retinal necrosis (BARN), probably secondary to
      varicella-zoster virus (VZV) infection as IgM antibodies were detected in the
      serum. Intravenous acyclovir and ganciclovir limited the spread of necrosis, but
      to prevent recurrence he was maintained on oral acyclovir. A left cataract
      developed 17 months later which was extracted and replaced with a heparin surface
      modified intraocular lens. Intraocular specimens removed at the time of surgery
      were analysed by the polymerase chain reaction (PCR) using primers specific for a
      number of the herpes group of viruses, but no herpesviral DNA could be detected.

PMID- 7642340
TI  - Cuba: response of medical science to a crisis of optic and peripheral neuropathy.
AB  - We made two trips to Cuba, as part of an invited international delegation, to
      investigate an epidemic of optic neuropathy-induced blindness. We worked closely
      with Cuban scientists and clinicians in their efforts to understand and then deal
      with 50,000 cases of blindness and an entire population at risk. This gave an
      unparalleled opportunity to understand the Cuban system of ophthalmologic health
      care and, in particular, to appreciate the responses of the scientific and health
      care communities to this crisis. Several features of the very different Cuban
      medical and scientific infrastructure were both problematic and advantageous as
      they affected the Cuban efforts to understand, contain and treat this remarkable
      epidemic.

PMID- 7642341
TI  - Low prevalence of trachoma in the south western part of Saudi Arabia, results of
      a population based study.
AB  - Trachoma remains one of the world's leading causes of blindness. A population
      based survey of the prevalence of trachoma was conducted in the South Western
      part of Saudi Arabia in the period of between July and November 1991. Overall,
      7126 people were examined. Of these, 19 (0.26%) persons had active trachoma and
      35 (0.5%) people had inactive trachoma. Sequelae of trachoma included
      conjunctival scarring, trichiasis and corneal scarring. Among 635 subjects with
      visual impairment, 6 (0.95%) patients had visual impairment due to trachoma.
      Trachoma does not seem to be a major ophthalmic problem in this area and proper
      management of the complications of trachoma will exclude it from the causes of
      blindness and visual impairment in this part of Saudi Arabia.

PMID- 7642342
TI  - The Mongolian gerbil in experimental epilepsy.
AB  - The Mongolian gerbil is recognized as a suitable experimental model for studying
      epileptiform seizures. About 10-20% of the gerbils provided by animal breeders
      show convulsions when placed in a new laboratory environment or handled for drug
      administration. In this review, the usefulness of the gerbil is critically
      evaluated on the basis of the literature available and our experience. Since
      gerbils often react with seizures in response to external stimuli we utilized a
      blast of compressed air. Seven gerbils were tested once weekly, for 15
      consecutive weeks, and electroencephalographic (EEG) activity was recorded. When
      the animals were challenged by a blast of compressed air they developed seizures,
      but with varying intensity and frequency. In the first weeks the majority of
      gerbils did not show seizures but they began to be susceptible to the stimulus
      from the 5th or 6th week. Four out of 7 animals proceeded to more severe
      seizures, characterized by clonic-tonic components. The pattern of behavioral
      seizures was paralleled by changes in the EEG recording. Altogether, data
      available indicate that the gerbil model is interesting in ethological studies
      and may be useful for investigating the mechanisms underlying "spontaneous"
      seizures. In pharmacology, however, the model has some weaknesses which limit its
      application in the study of new and established antiepileptic drugs.

PMID- 7642343
TI  - Single locus mutations in mice expressing generalized spike-wave absence
      epilepsies.
AB  - Studies in mutant mice are beginning to reveal important general principles
      regarding the heredity of the spike-wave cortical synchronization trait. First, a
      defect at a single gene locus is sufficient to produce a generalized spike-wave
      seizure disorder. Second, the EEG pattern itself is genetically heterogeneous,
      and can arise from mutations in at least five independent loci. Third, the
      intervening cellular excitability mechanisms underlying the generation of spike
      wave cortical discharges are not identical. Fourth, each of the mutant genes
      gives rise to syndromes that can differ in their seizure frequency, sensitivity
      to antiepileptic drugs, and severity of the associated neurological phenotype.
      Fifth, primary defects can be distinguished from secondary cellular alterations
      resulting from pathological neuronal synchronization. The patterns of these
      secondary changes vary according to the specific mutant allele, and may give rise
      to distinctive secondary phenotypes. The reproducibility of these defined genetic
      models may facilitate age-dependent antiepileptic drug discovery by defining
      novel targets for therapy at different developmental stages of the seizure
      disorder.

PMID- 7642344
TI  - Genetic Absence Epilepsy in Rats from Strasbourg (GAERS).
AB  - In Genetic Absence Epilepsy Rats from Strasbourg (GAERS), 100% of the animals
      present recurrent generalized non-convulsive seizures characterized by bilateral
      and synchronous spike-and-wave discharges (SWD) accompanied with behavioural
      arrest, staring and sometimes twitching of the vibrissae. Spontaneous SWD (7-11
      cps) start and end abruptly on a normal background EEG at a mean frequency of 1.5
      per min. Drugs effective against absence seizures in humans suppress the SWD dose
      dependently, whereas drugs specific for convulsive or focal seizures are
      ineffective. Depth EEG recordings and lesion experiments show that SWD in GAERS
      depend on cortical and thalamic structures with a possible rhythmic triggering by
      the lateral thalamus; GABAA and GABAB receptors seem to play a critical role. SWD
      are genetically determined with an autosomal dominant inheritance. The variable
      expression of SWD in offspring from GAERS and control reciprocal crosses may be
      due to the existence of multiple genes.

PMID- 7642345
TI  - Reflex epilepsy in the Papio-papio baboon, particularly photosensitive epilepsy.
AB  - Papio-papio baboons may present two types of reflex paroxysmal manifestations: -
      Myoclonia and generalized seizures are induced by intermittent light stimulation
      in predisposed animals; this photosensitive epilepsy resembles that observed in
      some human patients; it involves mainly the cerebral cortex during myoclonia
      which are accompanied by EEG paroxysmal discharges, and the mesencephalic
      reticular formation during seizures; --Myoclonia of a different type, never
      accompanied by EEG paroxysmal discharged and never evolving into seizures, may
      occur during movement or agitation of predisposed animals; these myoclonia are
      considered "non-epileptic" since they do not involve the cerebral cortex but
      probably the lower brain stem; they resemble that observed in startle disease or
      in some human degenerative disorders. The paper demonstrates that these
      manifestations constitute two different entities with clinical and
      electrophysiological characteristics as well as pharmacological reactivities
      completely different one from the other. Their "epileptic" or "non-epileptic"
      nature is discussed.

PMID- 7642346
TI  - Developmental seizure models.
AB  - Seizures frequently occur in children. There are significant differences in the
      generation, expression and modification of seizures as a function of age. Animal
      models of epilepsy should depict these age-related differences. In this paper, we
      summarize the main features of generalized flurothyl, pentylenetetrazol,
      bicuculline and picrotoxin-induced seizures in adult and immature rats as well as
      the characteristics of focal seizures induced by amygdala kindling, systemic NMDA
      and kainic acid. Some of the models may be more advantageous for screening
      antiepileptic drug effects whereas other models may be more helpful in studying
      the basic mechanisms of epilepsy.

PMID- 7642347
TI  - Chemoconvulsant seizures: advantages of focally-evoked seizure models.
AB  - Studies of short and long-term changes in regional metabolism, blood flow, gene
      expression (including immediate early genes and genes for neurotrophic factors),
      sprouting and cell death following seizures are pivotal to an understanding of
      the neural networks responsible for the generation of seizures. At the same time,
      this information forms a basis for understanding the pathophysiology associated
      with chronic, recurrent seizures. Systemic chemoconvulsant seizure models,
      produced by systemically administered chemoconvulsant agents, although
      convenient, are plagued with difficulties which confound the interpretation of
      their effects on the nervous system. These difficulties include widespread direct
      cellular and physiological effects of the chemoconvulsant drugs, most of which
      are independent of seizures. In addition, numerous physiological changes occur as
      a secondary consequence of, or ancillary to, seizures, and it can be especially
      difficult to separate these effects from the direct effects of the propagated
      seizure discharge itself. Some of these difficulties can be overcome by the use
      of focally-evoked seizure models. Such models avoid the diffuse presence of drug
      throughout the CNS and thereby eliminate most of the direct cellular and
      physiologic actions of the drug apart from seizure-induction. Large regions of
      the brain distant from the focal site of drug application then can be examined
      for molecular, structural and physiologic changes uncomplicated by the presence
      of drug. Moreover, different focal sites of drug application can be compared to
      evaluate the specificity of the molecular changes to the neural network engaged
      in the seizure discharge. For example, limbic seizures, evoked by chemoconvulsant
      application into area tempestas, can be compared with brainstem convulsions
      evoked by chemoconvulsant application into inferior colliculus.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7642348
TI  - Chronic focal epilepsy induced by intracerebral tetanus toxin.
AB  - A single, minute dose of tetanus toxin injected into mammalian cerebral cortex
      induces a chronic epileptic syndrome. Seizures lasting up to 3 minutes occur
      spontaneously and intermittently for several weeks to months. The cellular
      mechanisms of this model have been studied in detail using brain slices in vitro.
      Initially the release of the inhibitory neurotransmitter, GABA, is blocked, but
      after 2-4 weeks, other mechanisms take over. Intrahippocampal tetanus toxin
      models human complex partial seizures (temporal lobe epilepsy). It results in
      consistent behavioural changes analogous with those seen clinically, in spite of
      the limited neuronal loss found in only 10-30% of rats. Treatment with
      carbamazepine ameliorates both the seizures and their behavioural consequences.
      Tetanus toxin provides a versatile and long-lasting model of focal epilepsies.

PMID- 7642349
TI  - The pilocarpine model of epilepsy.
AB  - The systemic administration of a potent muscarinic agonist pilocarpine in rats
      promotes sequential behavioural and electrographic changes that can be divided in
      three distinct periods: (a) an acute period that built up progressively into a
      limbic status epilepticus and that lasts 24 h, (b) a silent period with a
      progressive normalization of EEG and behaviour which varies from 4 to 44 days,
      and (c) a chronic period with spontaneous recurrent seizures (SRSs). The main
      features of the SRSs observed during the long-term period resemble those of human
      complex partial seizures and recurs 2-3 times per week per animal. Therefore,
      this novel and unique experimental approach may serve as a model of epilepsy
      mimicking the human condition.

PMID- 7642350
TI  - Kainic acid induced hippocampal seizures in rats: comparisons of acute and
      chronic seizures using intrahippocampal versus systemic injections.
AB  - Hyppocampal epilepsy is a recently defined syndrome occurring in 65% of all
      temporal lobe epilepsies as defined by: 1) electrographic (EEG) onset in the
      hippocampus (HC) prior to EEG seizures elsewhere, 2) post-resection hippocampal
      sclerosis and mossy fiber synaptic reorganizations and 3) relief of typical
      complex partial seizures after surgical resection of the hyppocampus. We used
      intrahippocampal kainic acid injections V2 in rats at different developmental
      ages (postnatal 7 through adult) to develop long term spontaneous HC EEG spikes,
      EEG seizures, and behavioral seizures. Split-screen video/EEG monitoring
      demonstrated that this intrahippocampal kainic acid model produced progressive
      development of: 1) ipsilateral interictal spikes, 2) later polyspike complexes,
      3) bilaterally-asynchronous EEG spiking, 4) unilateral HC EEG seizure onsets with
      occasional secondarily generalized spread to apposite HC and motor cortex to
      elicit complex partial seizures, and 5) in all seizing rats there was mossy fiber
      synaptic reorganization, even when injected at age 7 days. These results indicate
      that the intrahippocampal kainic acid injection model is similar to human
      hippocampal epilepsy.

PMID- 7642351
TI  - An experimental model of progressive epilepsy: the development of kindling of the
      hippocampus of the rat.
AB  - Kindling epileptogenesis was induced by periodic electrical stimulation of the
      Schaffer collateral/commissural pathway in the CA1 area of the rat hippocampus.
      The progressive nature of hippocampal kindling is demonstrated by a detailed
      description of the behavioral signs and the progressive increase of the after
      discharge duration in the course of kindling acquisition. Furthermore, the
      evolution of the alterations in the paired-pulse local evoked field potentials
      and the modifications of the GABAA receptor binding and of the expression of
      mRNAs encoding for the subunits of the GABAA and glutamate receptors are
      considered. Evidence is presented that during kindling opposite changes occur in
      the CA1 and the fascia dentata in terms of the balance between excitation and
      inhibition due to contrasting changes in GABA-mediated inhibitory function.

PMID- 7642352
TI  - Animal models relevant to human epilepsies.
AB  - Animal studies have significantly contributed to our understanding of
      epileptogenesis and action mechanisms of antiepileptic drugs. The relevance of
      animal models to human epilepsies depend on how faithfully they reproduce the
      clinical and EEG features of human forms. In principle the definition of animal
      model of epilepsies should be reserved to animals presenting with recurrent
      seizures, either spontaneous of experimentally induced, persisting over time.
      Therefore acute experimental procedures designed to induce seizure and in vitro
      preparations should be referred to as models of seizures and models of
      epileptogenic mechanisms respectively rather models of epilepsies. The adequacy
      of a given animal model to study basic mechanisms of epilepsies and/or drug
      efficacy depend on the type of information that the investigator want to draw
      from it.

PMID- 7642354
TI  - Critical review of the animal models of generalized epilepsies.
AB  - The state of the art for models of generalized seizures in animals is
      satisfactory, but improvable for what concerns primary generalized seizures of
      Petit-Mal type. Other models of secondary generalized seizures are available
      allowing acceptable ways of studying some mechanisms of epileptogenesis, and/or
      screening potentials new AEDs. For other forms of seizures, such as amyotonic
      fits, there are no models. By and large, models of epilepsy are lagging behind
      models of seizures as most of the former when reproduced in the laboratory are
      short lived. Spontaneously occurring epilepsies in cats should be studied more
      widely as they may provide a wide variety of epileptic conditions not dissimilar
      from the ones seen in humans. Overall, models of seizures and epilepsies are more
      advanced than the models of most neuropsychiatric conditions.

PMID- 7642353
TI  - An animal model of hypoxia-induced perinatal seizures.
AB  - Clinically, neonatal hypoxic encephalopathy is commonly associated with seizure
      activity. Here we describe a rodent model of cerebral hypoxia in which there is
      are age dependent effects of hypoxia, with hypoxia inducing seizure activity in
      the immature rat, but not in the adult. Global hypoxia (3-4% O2) induced acute
      seizure activity during a window of development between postnatal day (P5-17),
      peaking at P10-12. Animals which had been rendered hypoxic between P10-12 had
      long term decreases in seizure threshold, while animals exposed at younger (P5)
      or older (P60) ages did not. Antagonists of excitatory amino acid (EAA)
      transmission appear to be superior to benzodiazepines in suppressing the acute
      and long term effects of perinatal hypoxia, suggesting involvement of the EAA
      system in these phenomena. No significant histologic damage occurs in this model,
      suggesting that functional alterations take place in neurons when exposed to an
      hypoxic insult at a critical developmental stage. Future work is directed at
      evaluating molecular and cellular events underlying the permanent increase in
      seizure susceptibility produced by this model.

PMID- 7642355
TI  - The early identification of anticonvulsant activity: role of the maximal
      electroshock and subcutaneous pentylenetetrazol seizure models.
AB  - A number of widely different animal seizure models have been employed in the
      search for new and novel anticonvulsant drugs useful for the treatment of human
      epilepsy. At present, no single laboratory test will, in itself, establish the
      presence or absence of anticonvulsant activity or fully predict the clinical
      potential of a test substance. Of the many available animal models, the maximal
      electroshock (MES) and subcutaneous pentylenetetrazol (scPTZ) tests still
      represent the most commonly employed models for the routine screening and
      identification of new anticonvulsant drugs. This chapter will briefly describe
      how these two tests are conducted, their limitations and how they have
      contributed in the past and to the present day anticonvulsant drug discovery
      process.

PMID- 7642356
TI  - Feline generalized penicillin epilepsy.
AB  - Feline generalized penicillin epilepsy represents an experimental model of
      generalized spike-and-wave discharges occurring during clinical absence attacks.
      Spike-and-wave discharges of feline generalized penicillin epilepsy also have a
      pharmacological profile that is similar to that encountered in human absence
      attacks. Studies on the respective roles played by the thalamus and cortex in the
      generation of spike-and-wave discharges indicate that both structures are
      important in the elaboration of such generalized activity. Moreover, GABAA
      mediated, intracortical inhibitory mechanisms are preserved and eventually
      enhanced at a time when generalized spike-and-wave discharges of feline
      generalized penicillin epilepsy are recorded. A preservation of GABA-mediated
      mechanisms in pure absence epilepsy might explain the differences in prognostic
      outlook that characterizes this type of epilepsy from seizures in which GABAergic
      mechanisms break down (e.g., generalized convulsive and partial epileptic
      attacks).

PMID- 7642357
TI  - Reflex epilepsy of the fowl and its transfer to normal chickens by brain
      embryonic grafts.
AB  - The genetic photosensitive epilepsy of the Fayoumi chicken was transferred to
      normal chickens by in situ grafts at 2 days of incubation, of both the
      prosencephalic and mesencephalic brain vesicles taken from epileptic embryos.
      However, mesencephalic graft is sufficient to allow convulsions under sound
      stimulation. Typical EEG patterns are recorded in chimeras having the
      prosencephalon plus or not the mesencephalon. We conclude that, in this mutant,
      the whole neural tissue is affected, but the seizure generator is localized
      inside the mesencephalon, and specific sensory pathways are necessary for
      seizures to occur.

PMID- 7642358
TI  - Critical evaluation of animal models for localization-related epilepsies.
AB  - There are many forms of human partial seizures and many human localization
      related epilepsies. Idiopathic epilepsies undoubtedly have pathophysiologic
      substrates different from those of symptomatic epilepsies, and there is evidence
      that some forms of limbic epilepsy involve different epileptogenic mechanisms
      than neocortical epilepsies. Although these mechanisms are best studied and
      understood by direct investigations of patients, this is often impractical and
      experimental animal models are also necessary. The use of experimental animals
      requires that the relevance of each model to a human condition be determined.
      Human epilepsies are comprised of multiple component parts which can be modeled
      independently. For instance, acute animal models provide opportunities to study
      epileptic seizures, but chronic models are necessary for investigation of
      processes relevant to epileptic conditions, such as epileptogenesis, transition
      from interictal to ictal state, and long-term consequences of epilepsy.
      Interactions between localized epileptic activity and cerebral maturation can
      also be studied in the animal laboratory. Experimental animal models of human
      partial seizures and localization-related epilepsies can be used to further
      investigations on basic mechanisms that cannot be pursued in patients, and to
      develop hypotheses concerning the fundamental neuronal processes underlying
      epilepsy and epilepsy-related phenomena that subsequently can be validated in
      patients. In addition, it would be of great clinical utility to develop animal
      models of partial seizures or localization-related epilepsy that could be used
      cost-effectively to screen potential anti-epileptic drugs.

PMID- 7642360
TI  - Festschrift in memory of Dr Fred I. Gilbert, Jr.

PMID- 7642361
TI  - My guardian angel.

PMID- 7642362
TI  - Cholestatic hepatitis caused by esters of erythromycin and oleandomycin. 1962.

PMID- 7642359
TI  - The genetically epilepsy-prone rat (GEPR).
AB  - Two independently inbred strains of genetically epilepsy-prone rats (GEPRs) have
      been developed. GEPR-3s and GEPR-9s have moderate and severe degrees of seizure
      predisposition as well as expression, respectively. Seizure predisposition is a
      fundamental distinction between the normal and epileptic brain. Seizure
      predisposition in GEPRs and in humans with epilepsy includes spontaneous seizures
      and exaggerated seizure responsiveness and/or abnormally low thresholds to
      stimuli which also cause seizures in non-epileptic subjects. Activation of
      brainstem seizure circuitry by auditory input via the inferior colliculus causes
      electrographic and behavioral responses in GEPR-9s which replicates human
      generalized tonic/clonic seizures. Activation of brainstem seizure circuitry by
      input from forebrain seizure circuitry in GEPRs provides a newly discovered model
      of complex partial seizures with secondary generalization to tonic/clonic
      seizures. Thus, seizure predisposition in GEPRs offers a unique opportunity to
      study the human epilepsies that is not offered in studies of normal brain exposed
      to convulsant stimuli.

PMID- 7642363
TI  - Computers in medicine: emergence of a new technology. 1978.

PMID- 7642364
TI  - The ups and downs of computers. 1980.

PMID- 7642365
TI  - Using the computer in the doctor's office to enhance the quality if patient care.
      1990.

PMID- 7642366
TI  - What have we learned from the breast cancer detection demonstration project?
      1986.

PMID- 7642367
TI  - Screening of chest roentgenograms by a radiological assistant. 1971.

PMID- 7642368
TI  - Allied health personnel in cancer detection. Utilization of proctosigmoidoscopic
      technicians in detecting abnormalities of the lower bowel. 1974.

PMID- 7642369
TI  - Health exam plans. 1967.

PMID- 7642370
TI  - Multiphasic screening cut down to size. 1968.

PMID- 7642371
TI  - The Hawaii carrel--a modular approach to multiphasic screening. 1970.

PMID- 7642372
TI  - Comparison of health appraisals by nurses and physicians. 1970.

PMID- 7642373
TI  - Share-care clinics. 1976.

PMID- 7642374
TI  - The appropriate use of technology (particularly in medical problems of the
      elderly). 1990.

PMID- 7642375
TI  - Health maintenance organizations in Hawaii. 1972.

PMID- 7642376
TI  - Reorganization of medical practice: its influence on patient-physician
      relationships. 1969.

PMID- 7642377
TI  - Suggestions for 1992 service and cost improvements.

PMID- 7642378
TI  - The pursuit of excellence. 1962.

PMID- 7642379
TI  - [Scientific medicine and alternative medicine--are we failing to communicate?].

PMID- 7642380
TI  - [The tuberculid concept from the current viewpoint].
AB  - The concept of tuberculid was introduced by Darier in 1896. In contrast to "true"
      cutaneous tuberculosis, properties of the tuberculids were explained by an
      hyperergic response to myobacteria or their fragments released from a different
      site of manifest or passed tuberculous infection. Key features include a strongly
      positive tuberculin skin test, evidence of concomitant manifest or past
      tuberculosis, and prompt response to antituberculous therapy. The inability to
      culture M. tuberculosis or to demonstrate it microscopically from lesional
      biopsies, together with reports on tuberculid-like eruptions after BCG
      vaccination, supports this concept. Clinical manifestations are lichen
      scrophulosorum, papulo-necrotic tuberculids and erythema induratum of Bazin. The
      existence of tuberculids has been questioned, however, because the clinical and
      histological appearances are not always specific. An increasing number of case
      reports on tuberculids, new immunological tests and molecular biology-based
      techniques for the detection of mycobacteria have shed new light on the
      tuberculid concept.

PMID- 7642381
TI  - [The diagnostic value of antinuclear antibodies].
AB  - In this review we focus on the diagnostic importance of antinuclear antibodies
      (ANA), the biological function of the relevant autoantigens and on some
      methodological questions regarding the detection of ANA. The qualitative and
      quantitative evaluation of ANA has improved significantly in recent years with
      the introduction of several new test kits. A precondition for the rational use of
      those assays is knowledge of the diagnostic validity of the detected ANA with
      regard to the method used. ANA are autoantibodies that react with nucleic acids,
      protein-nucleic acid complexes and proteins of nuclei. The reasons for their in
      vivo production are unknown. ANA characterize several of the so-called connective
      tissue autoimmune diseases and their subtypes, either alone or in typical
      combinations. They differ significantly with regard to their prevalence and thus
      in their diagnostic validity. Specificity and prevalence do not correlate. ANA
      are not markers of disease activity except for antibodies against dsDNA. ANA
      levels can be interpreted correctly only in connection with clinical symptoms and
      other laboratory findings.

PMID- 7642382
TI  - [Genetic factors in the development and progression of malignant melanoma].
AB  - Exposure of the skin to ultraviolet irradiation is an important risk factor for
      the development of malignant melanoma, with UVA possibly playing an important
      role. Hereditary factors are also relevant. In the dysplastic nevus syndrome a
      genetic instability has been shown by different methods. In xeroderma pigmentosum
      the DNA repair defect is thought to be responsible for the high incidence of
      malignant melanoma. Frequent and non-random changes in certain chromosomes have
      been demonstrated in melanoma cells. These might contain sequences that control
      melanoma growth or melanoma suppressor genes. Especially the short arm of
      chromosome 9 is thought to contain one of these genes. This hypothesis is
      supported by a genetic linkage analysis in melanoma families and the
      demonstration of a germ line deletion of the locus 9p21 in a patient with eight
      primary melanomas. Changes in known tumor suppressor genes and oncogenes have
      also been reported in melanoma, but no consistent sequence of genetic events is
      known.

PMID- 7642383
TI  - [Disordered cutaneous microcirculation in diabetic neuropathic foot ulcer. Is
      modification by retrograde transvenous perfusion therapy possible?].
AB  - Due to the high risk of amputation they involve, diabetic neuropathic plantar
      ulcers (DNPU) must be regarded as a late manifestation/complication of diabetes
      mellitus. The suspected cause of these ulcers--disturbed cutaneous
      microcirculation--was studied by simultaneously measuring laser-Doppler flux
      (LDF) and cutaneous oxygen tension (pCUO2) in 14 patients with DNPU at three
      differently affected sites (dorsal forefoot, ulcer edge, lower leg). Dynamic
      tests (arterial occlusion, local hyperthermia) as a measure of vascular
      reactivity showed significantly reduced pCUO2 parameters coinciding with elevated
      LDF values. This reflects a shift of blood flow from the nutritive capillaries
      towards deeper vessels. Abolition of normal vasoconstriction in the arteriovenous
      shunt vessels by diabetic polyneuropathy is the assumed cause of increased AV
      perfusion, with a consequent rise in LDF values. In a subgroup of the above
      patients (n = 7) undergoing daily intravenous retrograde perfusion therapy (RVP)
      over 10 days several basic and dynamic microcirculatory functions were studied
      before and after this treatment. This subgroup showed on the forefoot and the
      lower leg a remarkable improvement of the microcirculatory parameters
      investigated, suggesting a better oxygen supply to the tissues after RVP therapy.

PMID- 7642384
TI  - [Skin ulcers in rheumatoid arthritis].
AB  - The appearance of severe ulceration of the skin in patients with rheumatoid
      arthritis is often associated with a tendency to progression of the underlying
      disease, involvement of internal organs and increased mortality. In the
      pathogenesis of such ulceration there are multiple causes for their development,
      persistence and tendency to poor healing. They include localized or generalized
      immune complex vasculitis, treatment with anti-inflammatory drugs and their side
      effects following the treatment, arterial and venous insufficiency, and
      mechanical factors. The management of severe ulceration requires stabilization of
      the underlying autoimmune disease, e.g. with high doses of glucocorticosteroids
      or other immunosuppressive drugs or plasmapheresis. Adjuvant treatment of pain
      with analgesics, improvement of blood perfusion and anti-inflammatory drugs
      should accompany the topical therapy of ulcers. After suppression of the local
      inflammatory reaction surgical intervention becomes necessary in most of the
      patients, and vascularized muscle flaps should be used in preference to
      meshgrafts or split skin grafts for extensive ulceration in rheumatoid arthritis.
      A hopeful perspective in the treatment of severe rheumatoid arthritis might be
      opened up with immunotherapy using monoclonal antibodies.

PMID- 7642385
TI  - [Sclerotic fibroma].
AB  - The clinical and histological diagnosis of sclerotic fibroma is important because
      of its potential association with Cowden's syndrome. Despite its distinctive
      histological appearance the lesion is often mis-diagnosed. We therefore present
      five of our own cases (2F, 3M) in which the tumor was located on the head (n =
      2), arm (n = 2) and leg (n = 1), respectively. Clinically, the lesions were white
      to flesh-colored firm nodules ranging in size from 0.5 to 1.2 cm. None of our
      patients revealed any clinical evidence of Cowden's disease. Simple surgical
      excision seems to be curative. Histologically, they were well-circumscribed but
      not encapsulated dermal nodules composed of stori-form-arranged sclerosing
      collagen bundles and vimentin-positive fibroblastlike cells interspersed in three
      cases by a number of alpha-smooth-muscle actin-positive myofibroblasts.
      Approximately 50% of cells (dermal dendritic cells (DD)) also reacted for factor
      XIIIa evenly scattered throughout the lesion in contrast to the very few (< 5%)
      CD34+ DD found predominantly at the lower border, thus possibly reflecting the
      distribution of these cells in normal skin. Sclerotic fibroma expands the
      spectrum of fibrous lesions that may express alpha-smooth-muscle actin.

PMID- 7642388
TI  - [Idiopathic elastolysis of the mid-dermis].
AB  - Idiopathic middermal elastolysis (IMDE) is a rare disorder with two different
      clinical presentations: type I lesions, with tiny wrinkles along skin cleavage
      lines in large confluent areas, and type II lesions, with small perifollicular
      papular protrusions. The histopathological picture is characteristic. IMDE is
      mainly seen in healthy young or middle-aged women. We describe a 60-year-old male
      patient with this disorder. The special interest of this case report is that
      there was no photosensitivity and no exacerbation with PUV therapy. IMDE is
      probably a special sort of elastolytic disorder, for which immunologic mechanisms
      seem possible.

PMID- 7642387
TI  - [Laser Doppler flowmetry in treatment follow-up of circumscribed scleroderma].
AB  - A 38-year-old male patient presented with circumscribed scleroderma (10 x 12 cm)
      in the left pectoral area. Hyperaemia of the skin in the area of the lilac ring
      (morphoea) was quantified by means of Laser-Doppler flux (LDF). At the lilac
      border of the morphoea LDF was increased to 420% of the reference value recorded
      for the unaffected skin of the contralateral side. Immediately after 13 days of
      antibiotic therapy (3 x 10 Mega penicillin G per day, i.v.) LDF normalized,
      though clinical changes were hardly apparent at this stage. By 6 months later,
      LDF was still in the normal range, and clinical signs, such as induration and
      hyperaemic redness, had also significantly improved. LDF measurements allow
      assessment of the therapeutic response to antibiotic therapy at a very early
      stage while the clinical situation is still unchanged.

PMID- 7642386
TI  - [Draining sinus in acne and rosacea. A clinical, histopathologic and experimental
      study].
AB  - The draining sinus is an unpleasant complication of acne conglobata, acne
      fulminans, acne inversa, rosacea conglobata and rosacea fulminans (pyoderma
      faciale). It is most common on the face, especially in the nasolabial folds, and
      on the neck below the mandibular line. Clinically, it is an elongated (2-5 cm
      long), elevated, periodically inflamed lesion, which sporadically discharges pus.
      The lesion persists with no tendency to spontaneous regression.
      Histopathologically, it consists of elaborate, epithelialized galleries connected
      to the skin surface at multiple points. It contains corneocytes, hairs, bacteria,
      serum, inflammatory cells and epitheloid granulomas. A surgical thread placed
      into the skin provides a model in which the generation of sinus tracts can be
      studied. Therapy is difficult. Intralesional corticosteroid injection,
      cryosurgery and isotretinoin are not always very effective. Sometimes complete
      excision of the lesion is necessary. The draining sinus is a special form of scar
      analogous to the pilonidal cyst.

PMID- 7642390
TI  - [IgG antibodies in food allergy].

PMID- 7642389
TI  - [Pachydermoperiostosis].
AB  - Pachydermoperiostosis (Friedreich-Erb-Arnold syndrome, Touraine-Solente-Gole
      syndrome) is a rare disease with an autosomal dominant mode of inheritance; it
      occurs almost exclusively in men. A report of typical pachydermoperiostosis in a
      31-year-old man is presented. Associated features were clubbed digits of the
      hands and feet with watch-crystal nails, thickening of the skin and soft tissues,
      hyperhidrosis of hands and feet, hyperplasia of the sebaceous glands with
      seborrhoea, gynaecomastia, and ophthalmic abnormalities that had been present
      since puberty. Radiological examination revealed periosteal hyperostosis of the
      short and long bones. Endocrine disturbances were not detected. Skin biopsies
      showed hypertrophy of the skin and skin appendages. Primary (idiopathic,
      hereditary) pachydermoperiostosis should be distinguished from secondary
      (symptomatic) forms of the disease, which are often associated with lung tumours.

PMID- 7642391
TI  - [Balneophototherapy].

PMID- 7642392
TI  - [Diagnosis of sleep apnea].

PMID- 7642393
TI  - [Current aspects of rhinitis research].

PMID- 7642394
TI  - [Tinnitus models for use in tinnitus counselling therapy of chronic tinnitus
      patients].
AB  - Tinnitus models are an integral part of tinnitus counselling. In cases with
      compensated tinnitus, counselling represents the only therapeutic measure
      necessary. In contrast, patients with uncompensated tinnitus require further
      therapy in the form of medication, tinnitus-maskers or psychotherapy. Sound
      processing along the peripheral and central auditory pathways is achieved by
      functional loops that direct mechanical, electrical or chemical information to
      various points in the pathway. Minor damage to a loop can cause destabilization
      of this finely balanced system and can induce tinnitus. Current peripheral
      tinnitus models are reviewed and discussed with respect to in vitro data from
      isolated outer hair cells of the guinea pig cochlea. Audiological findings of a
      patient with central tinnitus after brainstem surgery are discussed in view of
      central tinnitus models. Specific models for common hearing disorders, such as
      tinnitus with normal hearing, noise trauma, sudden hearing loss, toxic cochlear
      lesions, presbyacusis, acoustic neurinoma and Meniere's disease are presented for
      the ENT-surgeon involved with tinnitus-counselling.

PMID- 7642395
TI  - [Current aspects of frontal sinus surgery. I: Endonasal frontal sinus drainage in
      inflammatory diseases of the paranasal sinuses].
AB  - Most conditions of the frontal sinus requiring surgery can now be managed
      successfully by endonasal procedures. According to Draf, 3 types of frontal sinus
      drainage occur. Surgical techniques and indications are described. In a
      retrospective study we evaluated 132/648 patients who were on average 5 years
      postoperative. Forty-two patients had type 1, 43 patients had type 2 and 47
      patients had type 3 drainage. Endoscopy revealed a normal mucosa in 56-67%, whole
      polyps were found in 9-15%. There was no recurrence of an orbital or endocranial
      complication. According to our definition of surgical success, there was a
      success rate of 83.4% with type 1 drainage, 83.7% with type 2 drainage and 89.4%
      with type 3 drainage. If there was only little chance for successful endonasal
      surgery with type 3 drainage, an external osteoplastic frontal sinus operation
      was performed for definitive therapy.

PMID- 7642396
TI  - [Current aspects of frontal sinus surgery. II: External frontal sinus operation-
      osteoplastic approach].
AB  - Most inflammatory diseases of the frontal sinus requiring surgery can now be
      managed successfully by endonasal procedures. There remain, however, a number of
      problematic cases in which optimal exposure of the entire frontal sinus is
      required with possible complete removal of the mucous membrane and sinus
      obliteration. These remain indications for osteoplastic frontal sinus surgery.
      Depending on the individual situation, incisions can be chosen that are
      bicoronal, placed in a frontal crease or positioned below the eye-brow. Surgical
      techniques are described in detail. Osteoplastic surgery of the frontal sinus
      with fat obliteration is a reliable and safe method, particularly for management
      of so-called "difficult" frontal sinuses.

PMID- 7642397
TI  - [Cellular immune defect caused by postoperative irradiation in patients with
      squamous epithelial carcinomas of the upper aerodigestive tract].
AB  - The effect of locoregional postoperative radiation therapy on cellular immunity
      was investigated in 11 patients with head and neck cancer. During the course of
      the radiation therapy, total lymphocyte counts, CD8+ lymphocyte counts and
      especially CD4+ lymphocyte counts decreased significantly. The mean CD4+
      lymphocyte counts dropped from 739/microliters to 183/microliters (p < 0.001) and
      the average CD4+/CD8+ ratio also decreased significantly. In addition all
      patients showed impaired in vitro lymphocyte stimulation responses to several
      mitogens, with reductions found to be 10% to 50% of normal responses. Within 3-4
      weeks after radiation therapy there was a slight increase of CD4+ lymphocyte
      counts and the in vitro lymphocyte stimulation responses showed a tendency to
      normalization. These results indicate that locoregional postoperative radiation
      therapy in patients with head and neck cancer can induce a severe impairment of
      cellular immunity.

PMID- 7642398
TI  - [What should be recommended to a patient with a small radiologically suspected
      acoustic neuroma?].
AB  - OBJECTIVE: Criteria for therapeutic decision-making for intrameatal acoustic
      neurinomas that are suspected radiologically. DESIGN: Retrospective evaluation.
      PATIENTS: 114 surgically treated patients of the ORL Dept. of the University
      Erlangen-Nuremberg. OUTCOME MEASURES: Rate of complications. Preservation of
      facial nerve function and hearing. Preoperative time course of hearing.
      Reliability of radiological examination. Progression of symptoms and tumor
      growth. THERAPY: Surgical exposure and complete removal by the enlarged middle
      cranial fossa approach. RESULTS: In 47% of cases surgery confirmed a neurinoma
      limited to the internal auditory meatus. In 41%, tumors were larger than expected
      and had protruded into the cerebellopontine angle, indicating preoperative tumor
      growth during an average period of 5.4 months before surgery could be completed.
      The remaining 12% of patients were found to have a facial neurinoma, meningioma
      or non-tumorous lesion of the internal auditory canal. No permanent neurological
      deficits or fatalities occurred in any of the patients treated. Facial function
      was favorable in 88% and moderate pareses or synkineses occurred in 12%. The
      degree of hearing preservation depended on the preoperative situation. When the
      preoperative pure-tone average (at 0.5, 1, 2 and 4 kHz) was 30 dB or less,
      hearing levels of less than 90 dB could be preserved in 70% of cases. Findings
      also demonstrated that the complication rate and success of function preservation
      were similar to younger patients in patients older than 60 years (n = 21).
      Without surgery auditory acuity decreased by 10 dB per year. The volume of
      intrameatal neurinomas in 7/10 cases followed by MRI doubled during a median
      following time of 32 months. CONCLUSIONS: Acoustic neurinoma surgery by the
      enlarged middle cranial fossa approach is a safe procedure with low complication
      rates. The percentages of preservation of facial function and hearing can be
      excellent in cases with small tumors and good preoperative hearing. To date no
      parameter has been found to predict tumor growth or the time course for hearing
      loss in individual cases. Surgical ablation of radiologically suspected, small
      acoustic neurinoma by the transtemporal approach is recommended.

PMID- 7642399
TI  - [Results of recording frequency-specific acoustically evoked potentials with
      masked stimuli].
AB  - This study presents results of frequency-specific brainstem-evoked response
      audiometry using tone bursts in ipsilaterally notched noise. The technique used
      was described by Picton in 1979. Sixty-four children and adults were examined
      using this method. Differences between pure-tone behavioral thresholds and
      notched noise thresholds were calculated in 15 patients. Mean differences ranged
      from 1-3 dB and standard deviations from 8-17 dB for frequencies tested at 500,
      1000, 2000 and 4000 Hz. Differences in 12 children were calculated for thresholds
      obtained in a free-sound field. Maximum mean differences were 12 dB and standard
      deviations +/- 8 dB. These findings show that accurate frequency-specific
      thresholds can be obtained with brainstem-evoked response audiometry using tone
      bursts in notched noise.

PMID- 7642400
TI  - [Rare malignant laryngeal tumors].
AB  - Six rare malignant tumors were found in a group of 136 laryngeal malignancies
      accessioned between 1990 and 1992. The other 130 neoplasms were squamous cell
      carcinomas. One case each of an adenocarcinoma, a mucoepidermoid carcinoma and an
      undifferentiated carcinoma of nasopharyngeal type were of epithelial origin; a
      case of a malignant fibrous histiocytoma, a chondrosarcoma and a plasmacytoma
      were of mesenchymal origin. The clinical presentations, histological findings,
      and therapy employed in the six cases are discussed and the available literature
      reviewed.

PMID- 7642402
TI  - [Protection from the sun].

PMID- 7642401
TI  - [Laser surgical excision of a hypopharyngeal hemangioma using the CO2/Nd: YAG
      combination laser].
AB  - Hemangiomas of the upper aerodigestive tract may present a therapeutic challenge
      depending on their size, location and symptoms. We present a rare case of
      cavernous hemangioma of the aryepiglottic fold applaning in an adult. First
      symptoms were dysphagia and hoarseness. Surgical removal was performed with a
      CO2/Nd: YAG combination laser under microscopic control. After a regular
      postoperative course the patient has remained disease-free after a 2 year follow
      up period. We suggest the use of the CO2/Nd: YAG combination laser as preferred
      treatment in cases of exophytic hemangiomas, because of the favorable combination
      of excision with photocoagulation effects.

PMID- 7642403
TI  - Attention to silent ischemia may save lives.

PMID- 7642404
TI  - First-pass radionuclide cineangiography in diagnosis of coronary artery disease
      in patients older than 75 years: evaluation of sensitivity.
AB  - The sensitivity of first-pass radionuclide cineangiography in the detection of
      coronary artery disease was evaluated in 60 patients subdivided equally according
      to age younger than or older than 75 years. The mean age of group 1 (age > or =
      75 years) was 80.2 years +/- 5.3, and the mean age in group 2 (age < 75 years)
      was 62.0 years +/- 6.4. Disease prevalence in group 1 was 87% versus 80% in group
      2. Group 1 had higher prevalence of hypertension (67% vs 33%) and lower
      prevalence of typical angina pectoris (23% vs 55%). Overall sensitivity of first
      pass radionuclide cineangiography in group 1 was 93% versus 97% in group 2. Older
      patients had significantly lower maximal heart rates, workloads, and exercise
      durations, and age correlations were significant for exercise heart rate,
      workload, and exercise duration. Failure to achieve an adequate exercise endpoint
      had significant effect on testing sensitivity only in the younger subjects (98%
      vs 60%), indicating that sensitivity of first-pass radionuclide cineangiography
      is age independent.

PMID- 7642405
TI  - Obstructive sleep apnea: a multisystemic disorder.
AB  - Obstructive sleep apnea is a multisystemic disorder with pathologic sequelae that
      become apparent after a number of years. Patients with obstructive sleep apnea
      generally present with hypersomnolence, and diagnosis is eventually established
      through observation of the patient during sleep. Patients with obstructive sleep
      apnea snore loudly and experience nocturnal oxygen desaturation and repetitive
      disruptions from sleep that eventually lead to daytime hypersomnolence. Numerous
      complex interactive pathophysiologic events occur during each obstructive
      episode, and it is important for the clinician to be aware of the
      cardiopulmonary, neurologic, and anatomic abnormalities associated with this
      condition. The anatomic configuration of the pharynx and the physiologic response
      to occlusion of the upper airway have a major role in the pathogenesis of this
      disorder. Alveolar ventilation during an apneic episode is immediately reduced to
      zero, and the metabolic demands for oxygen must be met by oxygen stores within
      the body. With repetitive episodes of obstruction, the oxygen stores within the
      lungs are diminished and the rate of arterial oxyhemoglobin desaturation
      increases. During apneic episodes, the systemic blood pressure increases while
      heart rate and cardiac output decrease. Bradydysrhythmias have been noted with
      the obstructive apneic episodes, and ventricular dysrhythmias are associated with
      episodes of severe oxyhemoglobin desaturation. Coexisting cardiopulmonary or
      neuromuscular disease in patients with obstructive sleep apnea contributes to the
      development of hypoventilation, serious gas exchange derangement, and general
      cardiovascular instability.

PMID- 7642406
TI  - Antitrust laws and zones of safety.
AB  - As physicians explore areas of diversification and networking that can position
      them favorably for the changing health-care environment, their fear of running
      afoul of antitrust legislation handicaps them. A basic understanding of the
      intent of antitrust legislation and its application to healthcare is essential to
      physicians' strategic planning. This article traces the development of antitrust
      legislation and the regulatory agencies charged with its oversight. The authors
      review the first application of this legislation to the professions; distinguish
      per se violations from the rule-of-reason process; and summarize recent attempts
      by the Department of Justice and the Federal Trade Commission to provide useful
      guidance to healthcare providers in the market revolution.

PMID- 7642407
TI  - Hypothyroidism with concurrent Lyme disease.
AB  - Lyme disease can be seen as localized, disseminated, acute, or chronic and can
      mimic other, more serious diseases. Even though it is a multisystemic illness,
      very few spirochetes are present; yet, once established in the host, it can
      persist for years. The antibody response is slow and variable, and the spirochete
      is difficult to isolate from clinical specimens, even those obtained from the
      pathognomonic skin lesion. These variables, together with nonspecific symptoms,
      make the diagnosis of Lyme disease difficult. The author describes an unusual
      case of Lyme disease superimposed on severe primary hypothyroidism in which the
      thyroid disorder was so advanced and pronounced that the diagnosis of Borrelia
      infection could easily have been missed.

PMID- 7642408
TI  - Polarographic needle electrode measurements of oxygen in rat prostate carcinomas:
      accuracy and reproducibility.
AB  - PURPOSE: The oxygenation status of tumors may be important for predicting tumor
      response to therapy. Previous studies with the anaplastic (R3327-AT) and well
      differentiated (R3327-H) Dunning rat prostate tumors using indirect assays of
      tumor oxygenation indicated the relative hypoxic and radioresistant nature of the
      anaplastic tumor. We now report direct measurements of oxygen in these tumors
      made with the pO2 histograph to determine: (a) whether a significant difference
      in oxygenation status could be detected between them: (b) whether sequential
      measurements on the same tumor gave similar values; and (c) whether tumor
      oxygenation correlated with tumor volume. METHODS AND MATERIALS: R3327-AT and
      R3327-H tumors were grown in Fischer X Copenhagen rat to volumes of 1.0-7.0 cm3.
      Electrode measurements (100-200) were made in tumors in anesthetized animals
      along two parallel tracks. Repeat measurements were made at 1-5 days along
      different parallel tracks. Oxygen partial pressures of muscle tissue were
      measured and served as a normal tissue control. Statistical analyses were applied
      to determine whether tumor oxygen levels were different between the two tumor
      histologies, whether sequential measurements in the same tumor were reproducible,
      and whether tumor oxygenation correlated with tumor volume. RESULTS: The average
      median pO2 of the well-differentiated (n = 15) and the anaplastic (n = 15) tumors
      was 6.0 mmHg (SE +/- 1.3) and 2.2 mmHg (SE +/- 0.3), respectively. The average
      median pO2 of normal rat muscle (n = 15) was 23.6 mmHg (SE +/- 2.0). These values
      represent highly significant differences in oxygen concentration between the two
      tumors and rat muscle. The differences in average mean pO2 values were also
      highly significant. Repeat measurements in the same tumors on different days gave
      average median values of 4.7 and 2.2 mmHg in the R3327-H (n = 15) and R3327-AT (n
      = 15) tumors, respectively. For these repeat measurements, median pO2 values
      decreased in 15 and increased in 15 tumors, and were not significantly different
      from the first measurements. The average differences observed in median pO2 were
      37% (SE +/- 7) and 58% (SE +/- 10) for the R3327-H and R3327-AT tumors,
      respectively. No significant correlation was observed between pO2 levels and the
      tumor volumes investigated in this study. CONCLUSIONS: The median pO2 values of
      the anaplastic Dunning tumors were significantly lower than those of the well
      differentiated tumors (p < 0.001). Oxygen levels in both tumors were
      significantly lower than those measured in normal rat muscle (p < 0.00005).
      Repeat measurements of median pO2 in the same tumors were not significantly
      different for either tumor model (p > 0.5). The changes observed in pO2
      distributions within individual tumors from day to day may indicate true dynamics
      of its oxygenation status and/or the limits of electrode measurements, by
      sampling along only two insertion sites. The electrode measurements of pO2 in
      these tumor models are reproducible and confirm previously detected oxygenation
      differences between the anaplastic and well-differentiated tumors.

PMID- 7642409
TI  - Optical isomers of a new 2-nitroimidazole nucleoside analog (PR-350 series):
      radiosensitization efficiency and toxicity.
AB  - PURPOSE: A new 2-nitroimidazole nucleoside radiosensitizer, PR-350 (1-[1',3',4'
      trihydroxy-2'-butoxy]-methyl-2-nitroimidazole), has been reported to be as
      efficient as and less toxic than etanidazole. This compound is racemic, and it
      was recently optically resolved into two isomers, PR-68 (2'R,3'S type) and PR-69
      (2'S,3'R type). The other two isomers, PR-28 (2'S,3'S type) and PR-44 (2'R,3'R
      type), were asymmetrically synthesized. In the present study, we investigated the
      properties, sensitizing activity, and toxicity of PR-350 and the four optical
      isomers in comparison with those of other 2-nitroimidazole hypoxic cell
      radiosensitizers, etanidazole, KU-2285, KIN-804, and RP-170. Because PR-350 and
      PR-28 can be industrially synthesized, we evaluated whether either of these two
      drugs are suitable for further investigation. METHODS AND MATERIALS: In an in
      vitro study, EMT-6 cells were irradiated at a dose of 1-3 Gy under hypoxic
      conditions in the presence of the drugs at a concentration of 1 mM. A combined
      cytokinesis-block micronucleus and chromosomal aberration assay was performed. To
      assess the in vivo effects, colony assay and growth delay assay were performing
      using SCCVII tumor-bearing C3H mice. The mice received 16-24 GY 10-40 min after
      administration of 50-200 mg/kg of the drugs. Toxicity and pharmacokinetics in
      mice were also investigated. RESULTS: The sensitizer enhancement ratio (SER) in
      the in vitro cytokinesis-block micronucleus assay increased in the following
      order: PR-69 (1.27) approximately equal to PR-28 (1.31) approximately equal to PR
      44 (1.38) approximately equal to PR-350 (1.41) approximately equal to PR-68
      (1.47) < etanidazole (1.79) < KIN-804 (2.03) approximately equal to KU-2285
      (2.30). The SER at a dose of 200 mg/kg and at an interval of 20 min (optimal
      interval) in the in vivo-in vitro colony assay increased as follows: PR-44 (1.26)
      approximately equal to PR-28 (1.29) < PR-69 (1.34) approximately equal to
      etanidazole (1.35) approximately equal to PR-350 (1.36) < RP-170 (1.41)
      approximately equal to PR-68 (1.41) < KU-2285 (1.49). The growth delay assay also
      showed that PR-350 was less efficient than KU-2285 and more efficient than PR-28.
      PR-350 and the four isomers had similar reduction potentials, but PR-28 and PR-44
      were more hydrophilic than PR-68 and PR-69. The LD50 in mice were 5.8 g/kg for PR
      350, approximately 7 g/kg for PR-28, 4 g/kg for PR-68, and 6 g/kg for PR-44 and
      PR-69. The concentration of PR-28 in the murine sciatic nerve was lower than that
      of PR-350. CONCLUSION: In vivo radiosensitizing activity differed among the four
      optical isomers, which appeared to be due, at least in part, to differences in
      lipophilicity. Although PR-28 was the least toxic, its low sensitization
      efficiency does not warrant clinical trials. Among the PR compounds, PR-68
      appears to be most efficient, but optical resolution of PR-68 from PR-350 is
      expensive, and asymmetrical synthesis of PR-68 is not established. Therefore, PR
      350 seems to be most suitable for further investigation among the PR-350 series
      compounds, considering its higher efficiency compared with PR-28 and PR-44, and
      established synthesis.

PMID- 7642410
TI  - The activation of a specific DNA binding protein by neutron irradiation.
AB  - PURPOSE: To determine whether the quality of ionizing radiation is critical for
      activation of a radiation-specific DNA binding protein. METHODS AND MATERIALS: We
      have previously shown that after exposing Epstein Barr virus-transformed
      lymphoblastoid cells to ionizing radiation, a specific DNA binding factor appears
      in the nucleus apparently as a result of translocation from the cytoplasm. This
      protein binds to a number of different genomic sequences and a consensus motif
      has been identified. Because the protein was not activated by UV light, it was of
      interest whether high linear energy transfer (LET) radiation was capable of
      activation. RESULTS: We describe here the activation of a specific DNA binding
      protein by high LET neutron radiation. The protein binds a region adjacent to and
      overlapping with the distal repeat within a 179 base-pair fragment of the well
      characterized Simian Virus (SV40) bidirectional promoter/enhancer element. The
      appearance of the DNA binding activity was dose dependent and reached a maximum
      level by 90 min postirradiation. A reduction in DNA binding activity was evident
      at later times after irradiation. CONCLUSIONS: The specific nature of this
      response and the rapidity of activation may indicate a pivotal role for this
      protein in repair or in some other aspect of the cellular response to radiation
      damage.

PMID- 7642411
TI  - A comparison of biological effects of modulated carbon-ions and fast neutrons in
      human osteosarcoma cells.
AB  - PURPOSE: To compare the biological effects of a 135 MeV/u carbon-ion beam and 13
      MeV fast neutron beam using human osteosarcoma cells. METHODS AND MATERIALS: We
      have studied the clonogenic cell survival, recovery of potentially lethal damage
      (PLD) in plateau phase cells, and spheroid cure in multicellular spheroid after
      irradiation at various positions in the plateau and spread out Bragg peak (SOBP)
      of a 135 MeV/u carbon-ion beam and with 13 MeV neutrons. The carbon beam had a 4
      cm range in water and a range filter was used to produce a 3-cm extended-peak
      region. The reference radiation was 137Cs gamma-rays. RESULTS: The relative
      biological effectiveness (RBE) values for 10% survival level of plateau phase
      cells for carbon-ions at the position of plateau, proximal peak, midpeak, and
      distal peak within the SOBP, and neutrons were 1.71, 2.48, 2.63, 3.47, and 2.29,
      respectively. Corresponding RBE values at 1% level were 1.64, 1.93, 2.06, 2.49,
      and 2.05. The extent of recovery from PLD was reduced after carbon-ions at
      proximal peak, midpeak, and distal peak, and neutrons, although not substantially
      reduced after carbon-ions at plateau. The RBE values for 50% spheroid cure level
      of spheroids for carbon-ions at the position of plateau, proximal peak,
      midproximal peak, middistal peak, and distal peak within the SOBP, and neutrons
      were 1.69, 1.88, 1.87, 1.94, 2.03, and 1.90, respectively. CONCLUSIONS: The
      biological parameters measured all indicate an approximately comparable
      biological effectiveness between 75-80 KeV/microns carbon-ions of the SOBP and 13
      MeV neutrons in the human tumor model studied in vitro.

PMID- 7642412
TI  - Reduced blood flow increases the in vivo ammonium ion concentration in the RIF-1
      tumor.
AB  - PURPOSE: Previous studies from our laboratory have suggested that pooling of
      ammonium in tumor tissues may be caused by its inefficient removal due to the
      poor vasculature commonly found in tumors. The purpose of these experiments was
      to validate the relationship between tumor ammonium ion concentration and tumor
      blood flow, and to determine whether large concentrations of ammonium ion
      detected by Nuclear Magnetic Resonance (NMR) spectroscopy are either produced
      within the tumor or simply imported into the tumor through the blood stream.
      METHODS AND MATERIALS: To test this hypothesis, we reduced blood flow in
      subcutaneously grown Radiation Induced Fibrosarcoma-1 (RIF-1) tumors, either by
      creating partial ischemia with a bolus injection of hydralazine or by occlusion
      with surgical sutures. 14N and 31P NMR spectroscopy were used to detect the
      presence of ammonium, and to assess the bioenergetic status of the tumors,
      respectively. RESULTS: A correlation between ammonium ion concentration and
      PCr/Pi ratio was established for untreated tumors. An increase in the in vivo
      tumor ammonium ion concentration was observed for every tumor that experienced a
      reduction in blood flow caused by either hydralazine injection or suture
      ligation. Changes in ammonium ion concentration paralleled changes in the
      bioenergetics of hydralazine-treated tumors. CONCLUSION: Our results support the
      hypothesis that a reduction in tumor blood flow is responsible for the
      accumulation of ammonium in tumors, and that detected ammonium originated from
      within the tumor.

PMID- 7642413
TI  - Potency following high-dose three-dimensional conformal radiotherapy and the
      impact of prior major urologic surgical procedures in patients treated for
      prostate cancer.
AB  - PURPOSE: To assess the impact of high-dose three-dimensional conformal
      radiotherapy (3DCRT) on potency in patients treated for clinically localized
      prostate cancer and to identify factors that might predict the outcome of sexual
      function following treatment. METHODS AND MATERIALS: One hundred twenty-four
      consecutive patients treated with 3DCRT for localized prostate cancer at UCSF
      between 1991-1993 were included in this retrospective analysis. Patient responses
      were obtained from a mailed questionnaire, telephone interviews, or departmental
      records. Medial follow-up was 21 months. RESULTS: Sixty patients reported having
      sexual function prior to 3DCRT, including 47 who were fully potent and 13 who
      were marginally potent. Of the remaining 64 patients, 45 were impotent, 7 were on
      hormones, 1 was status-postorchiectomy, and 11 were not evaluable. Following
      3DCRT, 37 of 60 patients (62%) retained sexual function sufficient for
      intercourse. Of those with sexual function before irradiation, 33 of 47 (70%) of
      patients fully potent and 4 of 13 (31%) of patients marginally potent maintained
      function sufficient for intercourse (p < 0.01). Potency was retained in 6 of 15
      (40%) patients with a history of a major urologic surgical procedure (MUSP) and
      in 31 of 45 (69%) with no history of a MUSP (p < 0.04). Transurethral resection
      of the prostate was the MUSP in eight of these patients, with four (50%)
      maintaining sexual function. CONCLUSIONS: Patients who receive definitive 3DCRT
      for localized prostate cancer appear to maintain potency similar to patients
      treated with conventional radiotherapy. However, patients who are marginally
      potent at presentation or who have a history of a MUSP appear to be at increased
      risk of impotence following 3DCRT.

PMID- 7642414
TI  - Which is the most suitable number of photon beam portals in coplanar radiation
      therapy?
AB  - PURPOSE: Computer-controlled milling machines for compensator manufacture,
      dynamic multileaf collimators, and narrow scanned electron or bremsstrahlung
      photon beams have opened up new possibilities to shape nonuniform fluence
      profiles and have thus, paved the road for truly three dimensional (3D) dose
      delivery. The present paper investigates the number of beam portals required to
      optimize coplanar radiation therapy using uniform and nonuniform dose delivery.
      METHODS AND MATERIALS: A recently developed algorithm has been used for
      optimization of the dose delivery in such a way that the probability of achieving
      tumor control without causing severe reactions in healthy normal tissues becomes
      as high as possible. This method has been used to optimize the delivered dose
      distribution for an increasing number of beam portals to determine how many
      coplanar beam portals are desirable to safely achieve a good treatment outcome.
      Target volumes in the head and neck, thorax, and abdomen have been investigated.
      RESULTS: Nonuniform dose delivery allows a considerable improvement in the
      treatment outcome compared to uniform dose delivery. This is evident both from
      the probability of achieving complication-free tumor control and the value of
      relevant properties of the dose distribution, such as the mean value and the
      standard deviation of the mean dose to target volume and organs at risk. The
      results also show a close relationship between the dose distribution parameters
      and the probability of achieving complication-free tumor control. The level of
      complication-free tumor control first increases rapidly when the number of beam
      portals is increased, but already reaches a level of saturation after three to
      five beam portals. When the saturation level has been reached, the standard
      deviation of the mean dose to the target volume is around 3%. CONCLUSIONS: To
      achieve optimal expectation value of the treatment outcome, within an accuracy of
      a few percent as measured by the probability of achieving complication-free tumor
      control, it is generally sufficient to use three nonuniform beam portals. A very
      large number of coplanar beams may only raise the probability of achieving
      complication-free tumor control by 1 to 2%. However, good treatment outcome with
      three beam portals requires that the directions of incidence of the coplanar
      nonuniform beams are optimally selected. If, on the other hand, the treatment is
      performed using uniform beams, it is not possible, even with an infinite number
      of fields, to obtain as high a level of complication-free tumor control as with a
      few nonuniform beams. From an optimization point of view, it is sufficient to
      reach a relative standard deviation of the mean dose to the target volume of
      around 3%. Improved dose homogeneity beyond this level will, in general, not
      significantly improve the complication-free tumor control.

PMID- 7642415
TI  - Alternating chemo-radiotherapy in bladder cancer: a conservative approach.
AB  - PURPOSE: The aim of this Phase II study was to determine a bladder-sparing
      treatment in patients with invasive bladder cancer, allowing a better quality of
      life. Objectives were to test toxicity and disease-free and overall survival of
      patients given an alternated chemo-radiotherapy definitive treatment. METHODS AND
      MATERIALS: Seventy-six patients with bladder cancer Stage T1G3 through T4 N0 M0
      were entered in the same chemotherapy regimen (Cisplatin 20 mg/mq and 5
      Fluorouracil 200 mg/mq daily for 5 days) alternated with different radiotherapy
      scheduling, the first 18 patients received two cycles of 20 Gy/10 fractions/12
      days each; the second group of 58 patients received two cycles of 25 Gy/10
      fractions/12 days each (the last 21 patients received Methotrexate 40 mg/mq
      instead of 5-Fluorouracil). RESULTS: A clinical complete response was observed in
      57 patients (81%), partial response in 7 patients (10%), and a nonresponse in 6
      patients (9%). At a median follow-up of 45 months, 33 patients (47%) were alive
      and free of tumor. The 6-year overall survival and progression-free survival was
      42% and 40%, respectively. Systemic side effects were mild, while a moderate or
      severe local toxicity was observed in 14 patients and 13 patients (about 20%),
      respectively. CONCLUSION: Our conservative combination treatment allowed bladder
      sparing in a high rate of patients and resulted in a survival comparable to that
      reported after radical cystectomy.

PMID- 7642416
TI  - Evaluation of cognitive function in patients with limited small cell lung cancer
      prior to and shortly following prophylactic cranial irradiation.
AB  - PURPOSE: Cognitive deficits after treatment for small cell lung cancer (SCLC)
      have been attributed to prophylactic cranial irradiation (PCI). A prospective
      study of neuropsychological function was undertaken to document the evolution and
      magnitude of neuropsychologic deficits. METHODS AND MATERIALS: Thirty patients
      with limited stage SCLC who responded well (29 complete response (CR), 1 partial
      response (PR)) to combination chemotherapy plus thoracic irradiation or resection
      were studied with neuropsychological tests in the cognitive domains of
      intelligence, frontal lobe function, language, memory, visual-perception, and
      motor dexterity prior to a planned course of PCI. Nine patients had a neurologic
      history that could influence testing. RESULTS: An unexpected 97% (29 out 30) of
      patients had evidence of cognitive dysfunction prior to PCI. The most frequent
      impairment was verbal memory, followed by frontal lobe dysfunction, and fine
      motor incoordination. Of the patients with no prior neurologic or substance abuse
      history, 20 out of 21 (95%) had impairments on neuropsychological assessment.
      This neurologically normal group was just as impaired as the group with such a
      history with respect to delayed verbal memory and frontal lobe executive
      function. Eleven patients had neuropsychological testing 6 to 20 months after
      PCI; no significant differences were found from their pretreatment tests.
      CONCLUSIONS: A high proportion of neurologically normal patients was limited SCLC
      and favorable responses to combination chemotherapy have specific cognitive
      deficits before receiving PCI. Short-term (6 to 20 months) observations after PCI
      have shown no significant deterioration.

PMID- 7642417
TI  - Chemoradiation in advanced nonsmall cell lung cancer.
AB  - PURPOSE: Resectability, local control, and survival were evaluated in advanced
      stage nonsmall cell lung cancer treated with simultaneous chemoradiation therapy
      delivered in an accelerated, interrupted twice-a-day schedule. METHODS AND
      MATERIALS: Forty-seven consecutive patients with Stage IIIA or IIIB nonsmall cell
      lung cancer, consenting to participation in the study, received cisplatin, 30
      mg/m2 for 3 days, etoposid, 80 mg/m2 for 3 days, and 5-fluorouracil, 900 mg/m2
      for 4 days. Radiation therapy consisted of 2 Gy given twice a day for 5 days. Two
      weeks rest was planned between cycles. Patients were evaluated for resectability
      after the second cycle. Any patient with unresectable tumor received a third
      cycle of treatment. RESULTS: Forty-seven patients were evaluable for acute
      toxicity: eighteen (38%) required an extended rest period for esophagitis or low
      blood count; 3 (6%) had sepsis, of whom 1 (2%) expired. Three patients (6%) had
      multiple blood transfusions for low hemoglobin. Median follow-up is 23.6 months,
      with a range of 10-49 months. Nine patients (19%) failed locally; 15 (32%) had
      local and distant failure; 7 (15%) failed only at distant sites. Twelve patients
      (25.5%) are alive with no evidence of disease; 4 patients were lost to follow-up
      with disease. The 2-year actuarial survival is 49%, and the 4-year is 28.2%.
      CONCLUSION: Simultaneous chemoradiation is well tolerated with acceptable
      toxicity. The overall 2- and 4-year actuarial survival is somewhat better than
      that reported in the literature. Resectability in Stage IIIB patients was not
      increased with this regimen nor was any surgical specimen free of cancer. The 47%
      distant failure rate is not different from those reported by others.

PMID- 7642418
TI  - High-dose therapy and autologous bone marrow transplantation for Hodgkin's
      disease patients with relapses potentially treatable by radical radiation
      therapy.
AB  - PURPOSE: A retrospective review evaluated the results of autologous bone marrow
      transplantation (A-BMT) for patients with relapsed Hodgkin's disease (HD) who
      were potentially treatable by radical radiation therapy (RRT). METHODS AND
      MATERIALS: Evaluated patient cases met the following criteria: initial treatment
      with chemotherapy (with or without involved field radiation therapy < 25 Gy); no
      history of bone marrow or extensive lung involvement; no current or previous
      evidence of systemic metastases except liver; radiation therapy used with salvage
      chemotherapy for prior relapse would not preclude use of RRT (e.g., > 20 Gy to
      spinal cord); HD at time of salvage therapy limited to lymph nodes, Waldeyer's
      ring, liver, spleen, direct extension sites, and/or one lung. RESULTS: There were
      23 A-BMT patients treated between 1986 and 1991 who fulfilled the criteria. Three
      (13%) patients died from treatment-related complications and eight (35%)
      developed nonfatal Grade 3-4 complications. The 3-year actuarial disease-free
      survival rate was 61%. The 3-year disease-free survival rate was 55% for the nine
      patients with at least one prior disease-free interval (DFI) > 12 months, 67% for
      nine patients with DFI < 12 months, and 60% for five induction failure patients
      (p > 0.10). These results are comparable to retrospective studies of RRT results
      in selected relapsed HD patients. CONCLUSIONS: Long-term disease-free survival is
      frequently possible with either A-BMT or RRT in appropriately selected relapsed
      HD patients. In considering treatment options, important prognostic factors
      include initial stage of disease, number of prior relapses, DFI, and extent of
      relapsed disease.

PMID- 7642419
TI  - The achievement of isoeffective bronchial mucosal dose during endobronchial
      brachytherapy.
AB  - PURPOSE: The use of endobronchial brachytherapy in the treatment of lung cancer
      is increasing due to the more widespread availability of high dose rate
      afterloading equipment. The complications include small airway (segmental and
      small lobar bronchi) fibrosis, stenosis, and obstructive complications in
      addition to hemorrhage. A progressive reduction in the diameter of the bronchial
      lumen occurs at each division of the bronchial tree. If uniform dwell times along
      a bronchial catheter treatment length are used, this will result in higher doses
      being given to the bronchial mucosa in the distal part of the treatment volume
      where the brachytherapy source mucosa distances are smaller, and underdosage
      proximally, where the source mucosa distances are larger. METHODS AND MATERIALS:
      The known mathematical relationships of the sequential reductions in the diameter
      of the bronchial lumen have been incorporated into two methods of optimization,
      which have been compared to uniform dwell times along a treatment length from
      trachea to segmental bronchus. RESULTS: The resulting isodose plots are
      presented, and demonstrate the extent of the overdosage distally, and the
      underdosage proximally when using uniform dwell times, and the achievement of
      isoeffective mucosal doses when using differential dwell times. CONCLUSION: This
      refinement in brachytherapy technique offers the potential for reduced normal
      tissue complications and possibly improved tumor control by reducing overdosage
      and underdosage, respectively.

PMID- 7642420
TI  - Treatment planning optimization by conjugate gradients and simulated annealing
      methods in stereotactic radiosurgery.
AB  - PURPOSE: This paper presents a new optimization method of treatment planning in
      linac stereotactic radiosurgery. METHODS AND MATERIALS: On a workstation
      integrating x-rays, computed tomography (CT), magnetic resonance imaging (MRI),
      and digital subtracted angiography (DSA) images, we first determine the outlines
      of the target volume and surrounding healthy tissues to spare. To achieve
      complete optimization of the treatment plans, this method decomposes the
      optimization process in two steps. The position of the isocenters and the
      diameter of the collimators are first deduced by a conjugate gradients method,
      from the position and size of ellipsoids or spheres modeling the target volume.
      The other irradiation parameters, such as the isocenter dose, the aperture, and
      the weight of each irradiation plane and of their irradiation sectors are finally
      deduced by a simulated annealing optimization algorithm. RESULTS: The system can
      perform multitarget/multisector treatment plans that are automatically obtained
      in a satisfactory time (as a rule, 20 min for a two-target irradiation), much
      faster than the time needed for a manual treatment planning. We present the
      results in two cases: the simulation of a single-target treatment and a two
      target real treatment with constraints. In these two cases, we can control the
      dose received by target and sensitive volumes. CONCLUSION: This method achieves
      an excellent conformation of the estimated isodose curves with the outlines of
      the target volume, which allows us to avoid the surrounding healthy tissues,
      thanks to the different weighting factors given on each volume concerned
      according to the importance we grant to each of them.

PMID- 7642421
TI  - High dose rate brachytherapy for prevention of restenosis after percutaneous
      transluminal coronary angioplasty: preliminary dosimetric tests of a new source
      presentation.
AB  - PURPOSE: Balloon dilatation of coronary artery stenosis has become a standard
      treatment of atherosclerotic heart disease. Restenosis due to excessive intimal
      cell proliferation, which subsequently occurs in 20-50% of patients, represents
      one of the major clinical problems in contemporary cardiology, and no
      satisfactory method for its prevention has thus far been found. Because modest
      doses of radiation have proved effective in preventing certain types of abnormal
      cellular proliferation resulting from surgical trauma, and brachytherapy has
      already been used successfully after dilation of peripheral arteries, development
      of a radioactive source suitable for coronary artery applications would be of
      great interest. METHODS AND MATERIALS: Nonradioactive flexible yttrium-89 wires
      (diameter of 0.15 and 0.26 mm) were activated within the thermal neutron flux of
      an experimental reactor. Standard angioplasty balloons (2 cm long, 2.5 mm in
      diameter when inflated) were inserted for dosimetry into a specially manufactured
      tissue equivalent phantom. Four wells, drilled perpendicular to the axis of the
      balloon, allowed for the insertion of thermal luminescent dosimeters (TLDs; 2 mm
      of diameter) and spacers. The angioplasty balloon was inflated with air or with
      contrast media. Radioactive yttrium-90 wires were left in the central lumen of
      the balloon for 2 min. Doses at the surface of the balloon, and at 1, 2, and 3 mm
      were determined from TLD readings. RESULTS: Doses obtained at the surface of the
      balloon, for a 2-min exposure for the 0.26 mm wire (balloon inflated with air)
      and the 0.15 mm wire (air or contrast), were 56.5 Gy, 17.8 Gy, 5.4 Gy,
      respectively. As expected for a beta emitter, the fall-off in dose as a function
      of depth was rapid. External irradiation from the beta source was negligible.
      CONCLUSIONS: Our experiments indicate that the dose rates attainable at the
      surface of the angioplasty balloon using this technique allow the doses necessary
      for the inhibition of intimal cell proliferation to be reached within a
      relatively short period of time. The thin yttrium-90 wires are very easy to
      handle, and their mechanical and radioactive properties are well suited to the
      requirements of the catheterization procedure.

PMID- 7642422
TI  - A radiation overdose incident: initial data.
AB  - PURPOSE: To estimate tolerance limits for irradiated human tissues by evaluating
      reactions observed in 426 patients who had received significant overdoses from an
      improperly calibrated cobalt unit. METHODS AND MATERIALS: A data file was
      designed to store essential technical and dosimetric information sufficient to
      analyze the response, estimate complication rates, and derive dose-response
      functions, using hierarchical region, system, and organ coding protocols.
      RESULTS: A total of 795 discrete target tissues had been irradiated in 426
      evaluable subjects studied. In 183 patients who survived beyond 1 year, there
      were 62 (34%) with immediate severe complications in 386 irradiated sites
      including brain, spinal cord, skin, oropharyngeal mucosa, colon, and rectum.
      CONCLUSION: This unique data set includes responses to high doses and unusual
      fractionation beyond the range of conventional clinical experience. It provides a
      resource for estimating human tissue tolerance limits, for testing clinically
      relevant radiobiological models and for developing new optimization algorithms.

PMID- 7642423
TI  - Photoneutrons from medical linear accelerators--radiobiological measurements and
      risk estimates.
AB  - PURPOSE: To assess the oncogenic potential of the photoneutrons produced by high
      energy medical linear accelerators. METHODS AND MATERIALS: An established line of
      cells of rodent origin (C3H 10T1/2) was used to assess the oncogenic potential of
      the radiation dose received in the breast of an anthropomorphic "randoman"
      phanton, while the cervix received a dose of 70 Gy. Experiments were performed at
      6 MV, below the threshold for the production of photoneutrons, and at 20 MV where
      the dose includes about 0.01 Gy of photoneutrons as well as scattered x-rays.
      RESULTS: A significantly higher transformation incidence was observed for the 20
      MV machine, consistent with the measured neutron dose of about 0.01 Gy and a
      quality factor of 20. CONCLUSION: An estimate can be made of the additional
      deaths from second malignancies that might result from the photoneutrons
      generated by higher energy linear accelerators (Linacs), which must be offset
      against the possible improvements in survival that might result from the higher
      tumor doses made possible by the increased percentage depth doses.

PMID- 7642424
TI  - Neutron radiation and prostate cancer.

PMID- 7642425
TI  - Cytokine cascades in late normal tissue radiation responses.

PMID- 7642426
TI  - When becometh less more?

PMID- 7642427
TI  - Comments on the use of paclitaxel as a radiation sensitizer.

PMID- 7642428
TI  - Letter to the editor regarding Mackillop et al., IJROBP 32:531-539; 1995.

PMID- 7642429
TI  - Photon neutron mixed-beam radiotherapy of locally advanced prostate cancer.
AB  - PURPOSE: In this article we present the results of mixed-beam, photon/neutron
      radiation therapy in 45 patients with locally advanced, bulky, or postoperative
      recurrent prostate cancer treated at the University of Chicago between 1978 and
      1991. Survival, disease-free survival, local control, and long-term complications
      are analyzed in detail. METHODS AND MATERIALS: Between 1978 and 1991, 45 patients
      with locally advanced (> 5 cm State B2, Stage C, or Stage D1) prostate cancer
      underwent mixed-beam (photon/neutron) radiation therapy. Forty percent of the
      treatment was delivered with neutron irradiation at either the University of
      Chicago or Fermilab. Sixty percent of treatment was delivered with photons at the
      University of Chicago. Initially, the whole pelvis was irradiated to 50 photon Gy
      equivalent. This was followed by a boost to the prostate for an additional 20
      photon Gy equivalent. RESULTS: The median follow-up for patients in this series
      is 72 months. The overall 5-year actuarial survival was 72%, and the 5-year
      disease-free survival was 45%. Thus far, 18 patients have died. Eleven patients
      have died from prostate cancer and 7 from other medical illness. Twenty-seven
      patients are alive, and 12 of these patients have recurrent and or metastatic
      disease. The local control rate was 89% (40 out of 45). Histologic material was
      available on 18 patients following treatment (i.e., prostate biopsy in 16
      patients and autopsy in 2 patients) and was negative for carcinoma in 13 (72%).
      Significant Grade 3-5 complications occurred in 36% (16 out of 45) of the
      patients treated with mixed-beam radiation therapy and were related to dose and
      beam quality. Factors related to survival, disease-free survival, local control,
      and complications are analyzed. CONCLUSIONS: The survival and local control
      results of mixed-beam radiation therapy at the University of Chicago appear to be
      superior to those series using photon radiation in patients with locally advanced
      prostate carcinoma. Mixed-beam radiation therapy should remain an alternative to
      studies using dose escalation or implant techniques as a method to increase local
      control and survival at institutions with this capability. However, appropriate
      plans with high-energy neutrons are necessary to minimize complications.

PMID- 7642430
TI  - Ten-year results of the treatment of early-stage breast carcinoma in elderly
      women using breast-conserving surgery and definitive breast irradiation.
AB  - PURPOSE: The optimal management of breast cancer in elderly women is not well
      established. Therefore, the present study was undertaken to evaluate the outcome
      of breast cancer in elderly women treated with breast-conserving surgery and
      definitive breast irradiation. METHODS AND MATERIALS: An analysis was performed
      of 558 women age > or = 50 years treated with breast-conserving surgery and
      definitive breast irradiation for Stages I-II invasive carcinoma of the breast.
      Of the 558 total women, there were 173 elderly women > or = 65 years and a
      comparison group of 385 women age 50-64 years. Treatment for all women included
      complete gross excision of the primary tumor, pathologic axillary lymph node
      staging, and definitive breast irradiation. Adjuvant systemic chemotherapy was
      used in 18% (102 out of 558) of the overall group. Adjuvant tamoxifen was used in
      17% (94 out of 558) of the overall group. The median follow-up after treatment
      was 6.2 years (mean = 6.4 years; range = 0.1-15.4 years). RESULTS: Elderly
      patients age > or = 65 years and patients age 50-64 years were both found to have
      tumors with adverse prognostic features, including clinical T2 lesions (43 vs.
      34%, respectively; p = 0.055), estrogen receptor negativity (9 vs. 16%,
      respectively; p = 0.13), and progesterone receptor negativity (17 vs. 21%,
      respectively; p = 0.50). Pathologic axillary lymph node staging showed that 24%
      of the elderly women were node positive, including 8% with four or more positive
      nodes, which was not different from women age 50-64 years (p = 0.23). There was
      no difference between the two age groups for the rate of deaths from breast
      cancer at 10 years (13 vs. 13%, respectively; p = 0.71). However, there was a
      significant difference between the two age groups for the rate of deaths from
      intercurrent disease at 10 years (11 vs. 2%, respectively; p = 0.0006). There
      were no differences between the two age groups for the 10-year rates of overall
      survival (77 vs. 85%, respectively; p = 0.14), relapse-free survival (64 vs. 70%,
      respectively; p = 0.16), freedom from distant metastases (83 vs. 78%,
      respectively; p = 0.45), or local failure (13 vs. 12%, respectively; p = 0.60).
      CONCLUSIONS: These results have shown that breast carcinomas in elderly women are
      not indolent and have a number of adverse prognostic features. Breast-conserving
      surgery and definitive breast irradiation in elderly women age > or = 65 years
      achieves good outcomes for survival, freedom from distant metastases, and local
      control, which are comparable to women age 50-64 years. The causes of deaths in
      elderly women age > or = 65 years are from both breast cancer and intercurrent
      disease. Breast-conserving surgery and definitive breast irradiation should
      continue to be considered as a standard treatment option for appropriately
      selected elderly women with early-stage breast cancer.

PMID- 7642431
TI  - Subareolar breast cancer: long-term results with conservative surgery and
      radiation therapy.
AB  - PURPOSE: It has been suggested that patients presenting with breast cancers
      within 2 cm of the nipple areolar complex represent a relative contraindication
      to conservative management due to either a compromised cosmetic result associated
      with sacrifice of the nipple areolar complex, reluctance to include the entire
      nipple areolar complex in the conedown field, or increased risk of
      multicentricity. We have reviewed our experience of conservatively treated
      patients with specific reference to the subset of patients presenting with tumors
      within 2 cm of the nipple areolar complex. METHODS AND MATERIALS: Between January
      1970 and December 1989, 1014 patients with early stage breast cancer were treated
      at Yale-New Haven Hospital by excisional biopsy with or without axillary lymph
      node dissection. Of the 1014 charts reviewed, a total of 98 patients fulfilled
      the criteria of having a central/ subareolar breast cancer. Reexcision was
      performed on only 16 patients. Following conservative surgery, patients were
      treated with radiation therapy to the intact breast to a total median dose of 48
      Gy with conedown to a total of 64 Gy. adjuvant systemic therapy and regional
      nodal irradiation were administered as clinically indicated. RESULTS: As of
      December 1993, the median follow-up for the 98 patients in this study was 9.03
      years. The majority of patients had presented with either a palpable mass or a
      mammographically detected lesion. Three patients presented with Paget's disease,
      five with nipple discharge, and seven with nipple inversion. Ten of the 98
      patients had the nipple areolar complex sacrificed at the time of surgery, while
      the remaining 88 patients had the entire nipple areolar complex included in the
      conedown field. Four of these 88 patients had the nipple partially blocked during
      the electron conedown. There were no significant complications associated with
      including the entire nipple areolar complex within the conedown field to a median
      dose of 64 Gy. Six of the 98 patients experienced a local recurrence, three
      experienced a regional recurrence, and nine experienced distant metastasis. The
      actuarial 10-year survival (0.79 +/- 0.06), distant disease-free survival (0.88
      +/- 0.04) and breast recurrence-free survival (0.84 +/- 0.07) were not
      significantly different from those patients who presented with cancers in other
      parts of the breast. CONCLUSIONS: Patients presenting with subareolar breast
      cancers within 2 cm of the nipple areolar complex are suitable candidates for
      conservative surgery and radiation therapy. In the majority of patients in this
      study, the nipple areolar complex did not need to be sacrificed and could be
      safely included in the electron conedown field with acceptable complications and
      cosmesis. A subareolar breast cancer does not represent a relative
      contraindication to conservative management in patients with early stage breast
      cancer.

PMID- 7642432
TI  - The influence of radiotherapy on cosmetic outcome after breast conservative
      surgery.
AB  - PURPOSE: The influence of radiotherapy in the cosmetic outcome after conservative
      surgery for breast cancer was evaluated using an objective method of calculating
      the asymmetry between the two breasts. METHODS AND MATERIALS: One hundred and one
      patients treated with the same conservative surgery were evaluated for cosmetic
      outcome. Sixty-one of them received external radiotherapy (50 + 10 Gy) to the
      residual breast; the remaining 40 underwent surgery only. The aspect of the
      patients' breasts was objectively assessed for symmetry by means of a
      computerized technique. A subjective assessment of the cosmetic outcome was
      performed both by physician and patient. These objective and subjective
      assessments were compared in the two groups treated with or without radiotherapy.
      RESULTS: The results obtained did not show significant differences in terms of
      cosmetic outcome in the two groups. Skin telangectasia was noted in two
      radiotherapy patients, while hypertrophic breast scars were only noted in six
      nonirradiated patients. CONCLUSIONS: We found that standard radiotherapy does not
      seem to influence the symmetry and the cosmetic results in breast conservative
      treatment when compared to a similar group of patients with the same
      quadrantectomy procedure and no radiotherapy.

PMID- 7642433
TI  - The role of three dimensional functional lung imaging in radiation treatment
      planning: the functional dose-volume histogram.
AB  - PURPOSE: During thoracic irradiation (XRT), treatment fields are usually designed
      to minimize the volume of nontumor-containing lung included. Generally,
      functional heterogeneities within the lung are not considered. The three
      dimensional (3D) functional information provided by single photon emission
      computed tomography (SPECT) lung perfusion scans might be useful in designing
      beams that minimize incidental irradiation of functioning lung tissue. We herein
      review the pretreatment SPECT scans in 86 patients (56 with lung cancer) to
      determine which are likely to benefit from this technology. METHODS AND
      MATERIALS: Prior to thoracic XRT, SPECT lung perfusion scans were obtained
      following the intravenous injection of approximately 4 mCi of 99mcTc-labeled
      macro-aggregated albumin. The presence of areas of decreased perfusion, their
      location relative to the tumor, and the potential clinical usefulness of their
      recognition, were scored. Patients were grouped and compared (two-tailed chi
      square) based on clinical factors. Conventional dose-volume histograms (DVHs)
      (DVFHs) are calculated based on the dose distribution throughout the computed
      tomography (CT)-defined lung and SPECT-defined perfused lung, respectively.
      RESULTS: Among 56 lung cancer patients, decreases in perfusion were observed at
      the tumor, adjacent to the tumor, and separate from the tumor in 94%, 74%, and
      42% of patients, respectively. Perfusion defects adjacent to the tumor were often
      large with centrally placed tumors. Hypoperfusion in regions separate from the
      tumor were statistically most common in patients with relatively poor pulmonary
      function and chronic obstructive pulmonary disease (COPD). Considering all SPECT
      defects adjacent to and separate from the tumor, corresponding CT abnormalities
      were seen in only approximately 50% and 20% of patients, respectively, and were
      generally not as impressive. Following XRT, hypoperfusion at and separate from
      the tumor persisted, while defects adjacent to the tumor improved in several
      patients. In four patients who achieved a complete response scored by CT with
      chemotherapy prior to XRT, persistent hypoperfusion was present at and adjacent
      to the tumor site in three. Among 30 patients with cancers not arising in the
      lung (14 breast, 12 lymphoma, 4 others), perfusion defects were seen in only 4 (2
      adjacent and 2 apart). Recognition of decreases in perfusion mainly impacted on
      treatment planning for a few patients with poor pulmonary function and limited
      target volumes. DVFHs have been useful in beam selection for patients with marked
      perfusion heterogeneities. CONCLUSIONS: Lung perfusion scans provide functional
      information not provided by CT scans that can be useful in designing radiation
      treatment beams that minimize incidental irradiation of the function regions of
      the lung. This approach appears to be most helpful in patients with gross
      intrathoracic lung cancer, especially those with small targets and relatively
      poor pulmonary function. One limitation of this approach is that some of the
      defects adjacent to the tumor site reperfuse following treatment, indicating that
      these scans identify perfusion rather than potential perfusion. Three dimensional
      functional data can be used to generate DVFHs that may be more predictive of the
      physiological consequences of the radiation than conventional DVHs. Additional
      work is currently underway to test this hypothesis.

PMID- 7642434
TI  - Small cell lung cancer with and without superior vena cava syndrome: a
      multivariate analysis of prognostic factors in 408 cases.
AB  - PURPOSE: Patients with small cell lung cancer (SCLC) and superior vena cava
      syndrome (SVCS) are widely believed to have a grave prognosis. The purpose of
      this study was to determine the prognosis of patients with SCLC and SVCS as
      compared to SCLC without SVCS. METHODS AND MATERIALS: A retrospective analysis of
      408 cases of SCLC +/- SVCS was performed. Three- hundred and sixty showed no
      clinical signs of SVCS and 43 (11%) had SVCS; in 5 patients no adequate
      information was available about clinical signs of SVCS. All patients were
      classified as limited disease cases. About 98% received chemotherapy usually as
      the first treatment followed by radiotherapy. A median total dose of 46 Gy (range
      30 to 70 Gy) was given at 2.0 Gy per fraction five times weekly. A prophylactic
      cranial irradiation was applied if a complete remission was achieved after
      chemotherapy or after 30 Gy of irradiation. Kaplan-Meier survival curves are
      shown and comparisons were made by the log-rank and the Gehan/Wilcoxon test. To
      adjust for prognostic factors, a proportional hazards analysis was done. RESULTS:
      Patients without SVCS had 5-year survival rates ( +/- SE) and a median survival
      time (MST; 95% confidence intervals) of 11% +/- 2% and 13.7 months (12.7-14.5) in
      UICC Stage I to III; in Stage III the figures were 9% +/- 2% and 12.6 months
      (11.2-13.7). In comparison, SCLC with SVCS had 5-year survival rates of 15% +/-
      7% and MST of 16.1 months (13.8-20.5). The difference was significant in
      univariate analysis (Stage II disease: p = 0.008 by the log-rank test). In a
      multivariate analysis of all patients, Stage (Stage I + II > III; p = 0.0003),
      SVCS (yes > no; p = 0.005), and Karnofsky performance status ( < or = 70 < 80
      100%; p = 0.008) were of significant importance. CONCLUSIONS: SVCS is a favorable
      prognostic sign in SCLC. The treatment should be curatively intended.

PMID- 7642435
TI  - Total lymphoid irradiation in the treatment of early or recurrent heart
      transplant rejection.
AB  - PURPOSE: Recurrent acute cardiac allograft rejection is an important cause of
      repeat hospitalization and a major mode of mortality, particularly during the 6
      months immediately following transplant. Total lymphoid irradiation (TLI) has
      been shown experimentally to induce a state of partial tolerance when
      administered prior to transplantation. Anecdotal reports of clinical experience
      have also suggested efficacy of TLI in treatment of recurrent cardiac rejection.
      The purpose of this study is to evaluate the safety and efficacy of TLI for
      treatment of early or recurrent heart transplant rejection. MATERIALS AND
      METHODS: Between January 1990 and June 1992, 49 patients postallograft cardiac
      transplant were given courses of TLI for treatment of early or recurrent
      rejection after conventional therapy with Methylprednisolone, antithymocyte
      globulin, OKT3, and methotrexate. Two patients failed to complete their therapy
      and were not evaluated. Two other patients received a second TLI course, making a
      total of 49 courses delivered. Indications for TLI were early rejection (n = 5),
      recurrent rejection (n = 38), and recurrent rejection with vasculitis (n = 6).
      The dose goal of the TLI protocol was 8 Gy in 10 fractions given twice weekly.
      Three separate fields were used to encompass all major lymph node-bearing areas.
      The actual mean dose was 7 Gy (range 2.4-8.4 Gy), and the duration of treatment
      was 8 to 106 days. These variations were secondary to leukopenia or
      thrombocytopenia. RESULTS: The mean posttransplant follow-up is 15 +/- 1.2 months
      (maximum 27 months). Among patients initiating TLI within 1 month posttransplant
      (n = 15), the rejection frequency decreased from 1.83 episodes/patient/month pre
      TLI to 0.13 episodes/patient/month post-TLI (p < 0.001). For those who began TLI
      1-3 months after transplant (n = 21), rejection decreased from 1.43 to 0.10
      episodes/patient/month (p < 0.001). When TLI was started more than 3 months
      posttransplant (n = 11), the pre-TLI and post-TLI rejection frequencies were 0.67
      and 0.07/patient/month (p < 0.001), respectively. The reduced post-TLI rejection
      frequencies were maintained to 24 months. There was no increase in the frequency
      of infection after TLI, nor were there any deaths during or immediately following
      TLI. CONCLUSION: Total lymphoid irradiation is a safe and effective adjunct for
      prolonged control of early or recurrent cardiac rejection. Bone marrow
      suppression is transient in nearly all patients and is not associated with an
      increased incidence of infection. The long-term benefits, possible late
      deleterious effects, and the potential role of TLI as induction therapy remain to
      be elucidated.

PMID- 7642436
TI  - Testicular seminoma: a failure analysis and literature review.
AB  - PURPOSE: A retrospective analysis of 74 patients with pure seminoma, treated at
      the University of Florida between 1964 and 1989, was undertaken. METHODS AND
      MATERIALS: All patients received megavoltage irradiation, with chemotherapy
      reserved for salvage. At 10 years, the probability of relapse-free survival was
      91% for Stage I, 93% for Stage IIA, 83% for Stage IIB, and 75% for Stage III
      patients. RESULTS: There were seven recurrences, none of which occurred in
      irradiated areas. Only two of seven patients (29%) with recurrence were salvaged.
      CONCLUSION: A literature review revealed an increasing rate of mediastinal or
      supraclavicular recurrence, correlating with the size of the subdiaphragmatic
      disease, in Stage II patients who did not receive elective mediastinal
      irradiation. Recommendations are made regarding the role of elective mediastinal
      irradiation for Stage II disease. We conclude that patients with Stage I or II
      seminoma can have high cure rates when treated with radiotherapy alone. Patients
      with Stage III seminoma should be treated initially with cisplatin-based
      chemotherapy.

PMID- 7642437
TI  - A perpetual cascade of cytokines postirradiation leads to pulmonary fibrosis.
AB  - PURPOSE: Radiation-induced pulmonary reactions have classically been viewed as
      distinct phases--acute pneumonitis and, later, fibrosis--occurring at different
      times after irradiation and attributed to different target cell populations. We
      prefer to view these events as a continuum, with no clear distinction between the
      temporal sequence of the different pulmonary reactions; the progression is the
      result of an early activation of an inflammatory reaction, leading to the
      expression and maintenance of a cytokine cascade. In the current study, we have
      examined the temporal and spatial expression of cytokine and extracellular matrix
      messenger ribonucleic acid (mRNA) abundance in fibrosis-sensitive mice after
      thoracic irradiation. METHODS AND MATERIALS: Radiation fibrosis-prone (C57BL/6)
      mice received thoracic irradiation of 5 and 12.5 Gy. At Day 1, and 1, 2, 8, 16,
      and 24 weeks after treatment, animals were killed and lung tissue processed for
      light microscopy and isolation of RNA. Expression of cytokine and extracellular
      matrix mRNA abundance was evaluated by slot-blot analysis and cellular
      localization by in situ hybridization and immunochemistry. RESULTS: One of the
      cytokines responsible for the inflammatory phase (IL-1 alpha) is elevated at 2
      weeks, returns to normal baseline values, then increases at 8 weeks, remaining
      elevated until 26 weeks when lung fibrosis appears. Transforming growth factor
      beta (TGF beta), a proliferative cytokine, is elevated at 2 weeks, persists until
      8 weeks, and then returns to baseline values. In parallel with the cytokine
      cascade, the fibrogenic markers for CI/CIII/IV (collagen genes) correlate by
      showing a similar early and then later elevation of activity. For instance, the
      collagen gene expression of CI/CIII is a biphasic response with an initial
      increase at 1-2 weeks that remits at 8 weeks, remains inactive from 8 to 16
      weeks, and then becomes elevated at 6 months when collagen deposition is
      recognized histopathologically. CONCLUSION: These studies clearly demonstrate the
      early and persistent elevation of cytokine production following pulmonary
      irradiation. The temporal relationship between the elevation of specific
      cytokines and the histological and biochemical evidence of fibrosis serves to
      illustrate the continuum of response, which, we believe, underlies pulmonary
      radiation reactions and supports the concept of a perpetual cascade of cytokines
      produced immediately after irradiation, prompting collagen genes to turn on, and
      persisting until the expression of late effects becomes apparent pathologically
      and clinically.

PMID- 7642438
TI  - Desired competencies of doctorally prepared allied health faculty.
AB  - In 1994, a two-round adaptation of the Delphi method was used to assist deans of
      the Association of Schools of Allied Health Professions (ASAHP) institutional
      member schools offering programs at the baccalaureate level or higher to
      determine important competencies for future doctorally prepared allied health
      faculty. Thirty-six of the 68 deans invited to participate completed the second
      questionnaire. Statistical analysis on the frequency of responses and calculated
      mean responses, including one-sample Z-tests and adjusted p-values, identified 21
      important competencies. This information should be considered by universities in
      the development or modification of graduate program curricula for the preparation
      of allied health faculty.

PMID- 7642439
TI  - Actual and desired computer literacy among allied health students.
AB  - The purpose of this study was to examine the level of computer literacy among
      allied health students, with specific focus on physical therapy, occupational
      therapy, and respiratory therapy students, and to investigate the perceived
      differences between actual computer literacy and desired computer literacy. Two
      established measurement instruments were used to collect data from a sample of
      377 allied health students. T-tests and Pearson product-moment correlations were
      conducted to analyze the data. Results show that allied health students take very
      few computer courses, but they are generally aware of the applications of
      computers in the practice of allied health and they desire a higher level of
      computer literacy than they currently have.

PMID- 7642440
TI  - Position on allied health professions education and funding.
AB  - ASAHP recommends that the federal government should, as the largest consumer of
      health care, play a central role in partnership with state governments and
      private institutions in reducing shortages of allied health personnel.
      Furthermore, ASAHP believes that this role should encompass attracting students
      (particularly from minority and underserved portions of the population) both to
      academic allied health programs through the provision of entry-level traineeships
      and advanced programs which prepare allied health professionals for careers as
      educators and researchers. No federal programs were authorized specifically to
      support allied health education during the period from 1981 to 1989. PL 100-607,
      the Health Professions Reauthorization Act of 1988, authorized $6 million ($2
      million in each of three categories), but only $737,000 was appropriated in FY
      1990 for Allied Health Grants and Contracts. The Bureau of Health Professions
      subsequently received 122 proposals in February 1990, representing more than
      $10,000,000 in requests for this limited amount. Since then, the Bureau has
      received an average of 100 proposals for each annual funding cycle. In addition
      to providing continuation grants for existing projects, the Bureau is currently
      able to award an average of 10 new grants each year. The $3,935,000 appropriated
      for FY 1995 will be used to fund perhaps another 12 to 15 initiatives. ASAHP
      believes that substantially more financial assistance is required than what is
      currently being appropriated. Furthermore, the most suitable venue for the
      federal government to affect reductions in the shortage of allied health
      professionals is through the advanced training portion of the Section 766
      Program, which remains unfunded.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7642441
TI  - A chemical hygiene plan for allied health sciences academic and research
      laboratories.

PMID- 7642442
TI  - A national survey of admissions criteria and processes in selected allied health
      professions.
AB  - A national survey of admissions criteria and procedures was conducted for allied
      health programs in diagnostic medical imaging, health information management,
      nurse-midwifery, occupational therapy, physical therapy, and physician assistant
      education. From a sample of 462, 63.2% responded. The survey canvassed general
      program information, prerequisites, admissions procedures, and demographic
      trends. Respondents were primarily from public institutions with faculty actively
      involved in admissions. The most common prerequisites were anatomy/physiology,
      physics, biology, chemistry, and psychology; and the most frequently required
      admissions criteria were GPA, references, interviews, science GPA, and writing
      sample. Standardized tests were rarely utilized. The following were the major
      prerequisite characteristics and skills considered: academic skills,
      communication skills, problem-solving abilities, maturity/confidence, motivation,
      and work/study habits. Changing demographics were reported, including an increase
      in second-career, older, and ethnically diverse applicants. Also discussed were
      nontraditional and minority applicant admissions issues. Future research
      suggestions include use of noncognitive variables, and academic and clinical
      outcome studies. The utility of this information for validation/revision of
      admissions criteria are presented.

PMID- 7642443
TI  - The possible relationship between transient evoked otoacoustic emissions and
      organ of Corti irregularities in the guinea pig.
AB  - Otoacoustic emissions are believed to arise from an active process associated
      with the outer hair cells in the mammalian organ of Corti. They have been
      attributed to the presence of impedance discontinuities on the basilar membrane
      which might be caused by hair cell irregularities. To test this hypothesis we
      have investigated the possible relationship between transient evoked otoacoustic
      emissions (TEOAEs) and anatomical integrity in the organ of Corti. Click-evoked
      TEOAEs have been measured from the ear canals of normal, pigmented guinea pigs
      using an Otodynamics ILO88 analyser. Emissions were present in 18 out of 19
      animals tested and the major frequencies observed were consistently present in
      different measurements over periods of up to ten weeks provided recording
      conditions were satisfactory. The frequency spectra of the TEOAEs resembled those
      measured in humans but the latencies of the responses were considerably shorter.
      In one acute experiment, the TEOAEs were shown to be dependent on metabolic
      energy as they were lost rapidly following termination with an overdose of
      anaesthetic. In another case, evoked emissions of long duration (sustained) at
      about 1 kHz were obtained from both ears. All cochleae examined showed
      irregularities, especially patches of mainly apical outer hair cell loss of
      differing extents. However, there was no evidence that substantial lesions
      coincided consistently with the frequency regions corresponding to the major
      emissions. Nevertheless, it was noted that the total energy level of emissions
      was proportional to the total outer hair cell loss, except in one case, where the
      outer hair cell loss was substantial and the energy level of TEOAEs was
      considerably lower. Although there is no clear relationship between TEOAEs of
      specific frequencies and abnormalities at the corresponding cochleotopic location
      in the organ of Corti which could represent impedance discontinuities, the degree
      of irregularity may determine the overall emission level. This finding is
      consistent with the idea that emissions arise as a result of irregularity
      producing variations in the reflection coefficient.

PMID- 7642444
TI  - Morphological and functional preservation of the outer hair cells from noise
      trauma by sound conditioning.
AB  - Guinea pigs were sound conditioned to a low-level, long-term pure tone stimulus
      (1 kHz, 81 dB SPL, 24 days) before exposure to a traumatic noise (1 kHz, 105 dB
      SPL, 72 h). Auditory brainstem response thresholds and distortion product
      otoacoustic emissions were obtained at selected frequencies before sound
      conditioning and at day 1, 5, 10, and 15 during sound conditioning as well as on
      the final 24th day. Auditory brainstem responses at 1 and 2 kHz were not affected
      at any time during sound conditioning. The amplitude of the distortion product
      otoacoustic emission showed minor alterations (below 10 dB) at selected
      frequencies only during the initial stages (day 1, 5, and 10) of sound
      conditioning in some, but not all the animals. Distortion product amplitudes were
      similar to control values on the 15th and 24th day of conditioning. Surface
      preparations of the organ of Corti did not reveal any significant hair cell loss
      induced by sound conditioning. The effect of a traumatic exposure (1 kHz, 105 dB
      SPL, 72 h) on a control group and a sound conditioned group was determined. The
      distortion product otoacoustic emission amplitude measured 4 weeks after the
      cessation of the traumatic exposure revealed significant differences. The
      amplitude of the distortion product otoacoustic emission for the control group
      was depressed at all tested frequencies and at lower frequencies (2.8, 2.1, and
      1.75 kHz) the emissions did not show an increase in response to increases in
      intensity, of the primaries. The sound conditioned group showed increases in
      distortion product amplitude with increases in the intensity of the primaries for
      all tested frequencies and statistically significant reductions from the pre
      exposure values were not found. Surface preparations from the control group
      indicated that the traumatic noise exposure affected nearly 100% of the outer
      hair cells around the 14 mm distance from the round window. The sound conditioned
      group showed a significantly less (50%) outer hair cell loss than the control
      group. The sound conditioned group illustrated an altered pattern of damage after
      subsequent noise trauma. There were two distinct regions of outer hair cell loss,
      one being around the 16 mm distance and the other around the 12 mm distance from
      the round window. These results imply that the intrinsic properties of the outer
      hair cells and/or the organ of Corti have been altered by sound conditioning.

PMID- 7642445
TI  - Longitudinal and radial differences in the subsurface cisternal system in the
      gerbil cochlea.
AB  - Many features of cochlear anatomy vary systematically radially and longitudinally
      within the organ of Corti. There is limited evidence that along the longitudinal
      axis of the cochlea the thickness of the subsurface cisternal system in the outer
      hair cells (OHCs) changes. Similarly a radial gradient may exist. The thickness
      of the subsurface cisternal system in OHCs was measured in gerbils to determine
      if there are differences between the three rows of OHCs and in OHCs in different
      locations along the length of the organ of Corti. The results suggest that there
      is a longitudinal as well as a radial gradient of subsurface cisternal system
      thickness. These gradients are the inverse to those for efferent innervation of
      OHCs. It is possible that these differences may contribute to the increased
      susceptibility to trauma and ototoxic compounds characteristic of the innermost
      and basalmost OHCs.

PMID- 7642446
TI  - Laser-feedback measurements of turtle basilar membrane motion using direct
      reflection.
AB  - In mammalian hearing, the frequency-dependent spatial pattern of movement in the
      basilar membrane/organ of Corti complex forms the basis of frequency
      discrimination. This is not necessarily the case in lower vertebrates; the
      turtle, for example, has an electrical resonance mechanism in its auditory
      receptor cells that varies in best frequency from cell to cell. But how much, if
      any, of the frequency separation by the turtle is done mechanically by the
      basilar membrane complex? Attempts to find an investigative approach that avoided
      placing objects on the basilar membrane led to the rediscovery of laser-feedback
      interferometry. Laser-feedback interferometric investigations of the vibrational
      amplitude and phase of the turtle basilar membrane in response to imposed
      nanometer displacements of the eardrum reveal that the membrane reflects the
      broadly-tuned middle-ear filter characteristics. Phase-angle measurements of the
      basilar membrane as a function of frequency, and the best frequency of the
      obtained amplitude tuning curves, did not vary as a function of position within
      each specimen. Input-output functions of the basilar membrane were generally
      linear. The middle ear demonstrates a negative gain of 2-6 while the central
      region of the basilar membrane has a positive gain of 4-18 dependent on location
      and biological variability.

PMID- 7642447
TI  - The arrangements of F-actin, tubulin and fodrin in the organ of Corti of the
      horseshoe bat (Rhinolophus rouxi) and the gerbil (Meriones unguiculatus).
AB  - The composition of cytoskeletal elements in hair cells and non-sensory cells was
      studied in paraformaldehyde fixed cochleae of the horseshoe bat and the gerbil
      using phallotoxins and antibodies directed against actin, alpha-tubulin and
      fodrin. In both species, cryostat sections of the organ of Corti were studied
      using confocal fluorescence microscopy; in the bat, ultrathin sections were
      investigated using actin-immunoelectron and classical electron microscopy. F
      actin was found in stereocilia and cuticular plates of inner and outer hair cells
      (IHCs and OHCs) of both species. In fixed material from both species, no F-actin
      staining was detected in the cytoplasm or along the lateral cell membrane of
      OHCs, whereas in freshly isolated OHCs of the gerbil, a faint F-actin staining
      was detected along the lateral wall. In the bat, the patterns of F-actin staining
      were confirmed with actin-immunoelectron microscopy. The alpha-tubulin antibody
      strongly labeled IHCs of both species. They contained a complex network of
      microtubules especially in the neck portion. In the bat, OHCs showed no distinct
      alpha-tubulin reactivity, as would be expected given the scarcity of microtubules
      observed at the ultrastructural level. In the gerbil, alpha-tubulin reactivity
      was found throughout the OHC body with highest intensity in the cell apex. In
      Deiters cells, pillar cells and Boettcher cells of both species, F-actin and
      microtubules were colocalized at contact zones with the basilar membrane. In
      Deiters cups, F-actin staining was most pronounced in the basal turn of the bat
      cochlea. In the gerbil, a distinct baso-apical gradient was found in
      immunostaining properties and morphology of the Deiters cells. Intense fodrin
      reactivity was found in the cuticular plates and along the lateral cell membrane
      of both types of hair cells of the bat. Cytoplasmic fodrin staining was localized
      within the IHCs of the bat. In the gerbil, intense fodrin staining was only found
      in cuticular plates of hair cells and staining of the lateral cell membrane of
      hair cells was faint. A faint fodrin staining was also seen in Deiters cells of
      both species. The basic arrangement of the cytoskeletal elements in the bats
      organ of Corti is similar to that of other mammals, however, certain features
      suggest the presence of subtle differences in micromechanical properties: there
      is an increased concentration of microtubules in the neck portion of IHCs, an
      increase in the amount of F-actin within the Deiters cups and a reduced amount of
      microtubules in the OHCs.

PMID- 7642448
TI  - Analysis and classification of delay-sensitive cortical neurons based on response
      to temporal parameters in echolocation signals.
AB  - Echolocating bats generate an acoustic image of their target by processing target
      reflected echoes of their emitted biosonar pulses. Efforts in building
      computational models of auditory processing in the bat auditory system, using
      extensive neurophysiological data from cortical studies are challenged by the
      intrinsic complexity and the significant variability in neural response to
      stimuli. In this paper, we use a computerized method for the analysis and
      classification of delay-sensitive neurons to classify neurons from the auditory
      cortex of Myotis lucifugus, a species that echolocates with FM signals. The
      coefficients of the bi-linear fit to the best delay response surfaces (mean R2 =
      0.01) were used in classifying the neurons. Six classes were derived that
      corresponded to the four previously characterized neurophysiologically. The first
      class corresponded to delay-tuned neurons which exhibited a constant best delay
      at different pulse repetition rates and pulse durations. Three other classes
      corresponded to the different subtypes of tracking neurons which changed their
      best delay to one or both of these stimulus temporal parameters. Two additional
      classes were differentiated although their best-delay response were similar to
      either the delay-tuned or the duration and pulse-repetition rate sensitive class.
      Artificial delay-sensitive neurons built from the parameters of the centroid of
      each class, will serve a key role in the FM bat auditory system model that we are
      building.

PMID- 7642449
TI  - Critical bands and critical-ratio bandwidth in the European starling.
AB  - Critical bands (CB) and critical-ratio (CR) bandwidth were determined in five
      European starlings (Sturnus vulgaris) using a GO/NOGO procedure and the method of
      constant stimuli. Test-tone frequencies were 1, 2, 4, and 6.3 kHz. Critical
      ratios were independent of the level of the white noise masker. The lowest CR of
      21.8 dB was found at 1 kHz, and the CR monotonically increased on average by 2.3
      dB per octave. CR-bandwidths at a masker spectrum level of 41 dB were 151, 191,
      437, and 501 Hz at 1, 2, 4, and 6.3 kHz, respectively. With the exception of the
      test-tone frequency of 6.3 kHz, the size of the critical bands measured with a
      band-narrowing procedure was similar to that of the CR-bandwidth. CBs were 135,
      233, 345, and 1156 Hz at 1, 2, 4, and 6.3 kHz, respectively. A repeat measurement
      at 6.3 kHz with another speaker position yielded a CB of 860 Hz. The results of
      this psychoacoustic study in the starling are discussed with respect to
      comparative data from other vertebrates and to neurophysiological bandwidth
      measurements of tuning curves of auditory-nerve fibres.

PMID- 7642450
TI  - Autoradiographic labelling of P2 purinoceptors in the guinea-pig cochlea.
AB  - Two different radioligands were used to identify extracellular ATP binding sites
      specific to P2 purinoceptors in guinea-pig cochlear tissue. Deoxyadenosine 5'
      (alpha-[35S]thio)triphosphate ([35S]dATP alpha S; 10 nM) provided a high activity
      probe for the P2y purinoceptor subtype on the basis of selective block by 2
      methylthio-ATP (2MeSATP; 100 microM). [3H]alpha, beta-methylene-ATP (10 nM), a
      high affinity probe for a P2x purinoceptor subtype was selectively blocked by
      inclusion of the related compound beta, gamma-methylene-ATP (100 microM). Both
      probes labelled the organ of Corti, stria vascularis and spiral prominence
      regions. The P2x purinoceptor probe also bound to lateral wall tissue below the
      spiral prominence and insertion point of the basilar membrane within the scala
      tympani compartment, a region which failed to show significant binding using
      [35S]dATP alpha S. Frozen sections of whole cochlea permitted analysis of
      radioligand binding to the cell body region (spiral ganglion in Rosenthal's
      canal) of the primary auditory afferents and the auditory nerve itself, which
      lies within the central region of the modiolus of the cochlea. Both these regions
      exhibited 2MeSATP blockable [35S]dATP alpha S binding whereas specific [3H]alpha,
      beta-methylene-ATP binding was absent from spiral ganglion and minimal in the
      auditory nerve region. These results demonstrate a mixed P2 purinoceptor
      distribution in cochlear tissues and suggest that complex purine-mediated
      neurohumoral mechanisms may influence cochlear function at a number of sites.

PMID- 7642451
TI  - Ion transport mechanisms responsible for K+ secretion and the transepithelial
      voltage across marginal cells of stria vascularis in vitro.
AB  - It has long been accepted that marginal cells of stria vascularis are involved in
      the generation of the endocochlear potential and the secretion of K+. The present
      study was designed to provide evidence for this hypothesis and for a cell model
      proposed to explain K+ secretion and the generation of the endocochlear
      potential. Stria vascularis from the cochlea of the gerbil was isolated and
      mounted into a micro-Ussing chamber such that the apical and basolateral membrane
      of marginal cells could be perfused independently. In this preparation, the
      transepithelial voltage (Vt) and resistance (Rt) were measured across marginal
      cells and the resulting equivalent short circuit current (Isc) was calculated
      (Isc = Vt/Rt). Further, K+ secretion (JK+,probe) was measured with a K(+)
      selective vibrating probe in the vicinity of the apical membrane. In the absence
      of extrinsic chemical driving forces, when both sides of the marginal cell
      epithelium were bathed with a perilymph-like solution, Vt was 8 mV (apical side
      positive), Rt was 10 ohm-cm2 and Isc was 850 microA/cm2 (N = 27). JK+,probe was
      outwardly directed from the apical membrane and reversibly inhibited by
      basolateral bumetanide, a blocker of the Na+/Cl-/K+ cotransporter. On the
      basolateral but not apical side, oubain and bumetanide each caused a decline of
      Vt and an increase of Rt suggesting the presence of the Na,K-ATPase and the
      Na+/Cl-/K+ cotransporter in the basolateral membrane. The responses to [Cl-]
      steps demonstrated a significant Cl- conductance in the basolateral membrane and
      a small Cl- conductance in the paracellular pathway or the apical membrane. The
      responses to [Na+] steps demonstrated no significant Na+ conductance in the
      basolateral membrane and a small Na+ or nonselective cation conductance in the
      apical membrane or paracellular pathway. The responses to [K+] steps demonstrated
      a large K+ conductance in the apical membrane. Apical application of 4,4'
      diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) and basolateral elevation of
      K+ caused an increase in Vt and a decrease in Rt consistent with stimulation of
      the apical K+ conductance. Similar observations have been made in vestibular dark
      cells, which suggest that strial marginal cells and vestibular dark cells are
      homologous and transport ions by the same pathways. Taken together, these
      observations are incompatible with a model for the generation of the endocochlear
      potential which ascribes the entire potential to the strial marginal cells
      [Offner et al. (1987) Hear. Res. 29, 117-124].(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7642452
TI  - Activity-dependent responses of developing cochlear nuclear neurons to
      microionophoretically-applied amino acids.
AB  - The experimental purpose of this investigation was to determine whether the
      efficacy of glutamate, N-methyl-D-aspartate (NMDA) and/or GABA is related to the
      activity state of neurons in the cochlear nuclear complex (CN). The hypothesis
      tested was that changes in discharge activity produced by glutamatergic and
      GABAergic ligands are, or may be, greater when neurons are stimulated at moderate
      to high acoustic levels compared to near threshold stimulation levels, when
      activity levels are high or low, respectively. All neurons from which discharge
      rate vs. sound pressure level curves were tested during simultaneous
      administration of amino acids exhibited characteristics commensurate with an
      activity-dependent system; at high sound levels, when discharge rates were
      elevated relative to rates produced by low level stimuli, both glutamate-induced
      increments and GABA-induced decrements in discharge rate were enhanced. The
      relationship between discharge rate and amino acid efficacy was a uniform
      property of neurons sampled throughout the first two postnatal weeks of
      development. In adults, preliminary indications are that activity-dependent
      neurotransmitter efficacy is characteristic of some cells, but not others. The
      activity-dependent nature of endogenous amino acid neurotransmission was
      demonstrated through the microionophoretic administration of NMDA and GABAA
      selective antagonists, D-alpha-aminoadipate (D alpha AA) and 2-amino-5
      phosphonovalerate (APV), and bicuculline (BIC), respectively. These results
      suggest that postsynaptic actions elicited by membrane receptors subserving amino
      acid neurotransmission within the CN are activity-dependent.

PMID- 7642453
TI  - Direct effects of reactive oxygen species on cochlear outer hair cell shape in
      vitro.
AB  - Reactive oxygen species (ROS) have been implicated in the ototoxicity of various
      agents. This study examines the effects of superoxide anion (O2), hydroxyl
      radical (OH.) and hydrogen peroxide (H2O2), on isolated cochlear outer hair cell
      (OHC) morphology. OHCs were superfused with artificial perilymph (AP) or AP
      containing a specific ROS scavenger, and then with AP, ROS system or scavenger
      plus ROS system for 90 min. The generation of ROS as well as the scavenging
      properties of other agents were confirmed by specific biochemical assays. Control
      cells decreased 4.8% in mean length, and showed no obvious membrane damage.
      Generation of O2. or OH. resulted in high rates (85.7 and 42.9%, respectively) of
      bleb formation at the synaptic pole, and decreased (O2., 15.2%; OH., 17.3%) mean
      cell length. Length change and bleb formation rate were H2O2 concentration
      dependent. 20 mM H2O2 led to 33.3% decreased mean cell length, and only 20% bleb
      formation; 0.1 mM H2O2 led to 83.3% bleb formation, with no length decrease.
      Superoxide dismutase, deferoxamine and catalase protected against O2., OH. and
      H2O2 effects, respectively. Bleb formation and diminished cell length likely
      represent differential lipid peroxidative outcomes at supra- and infranuclear
      membranes, and are consistent with effects of certain ototoxicants.

PMID- 7642454
TI  - Development of the otolith organs and semicircular canals in the Japanese red
      bellied newt, Cynops pyrrhogaster.
AB  - The sequence in which the otoliths and semicircular canals and their associated
      sensory epithelia appear and develop in the newt are described. Three-dimensional
      reconstruction of serial sections through the otic vesicle of newt embryos from
      stages 31 through 58 demonstrate the first appearance, relative position and
      growth of the otoliths. A single otolith is first seen in stage 33 embryos
      (approximately 9 days old); this splits into separate utricular and saccular
      otoliths at stage 40 (13 days). The lateral semicircular canal is the first to
      appear, at stage 41 (14 days). The anterior and posterior canals appear
      approximately one week later and the vestibular apparatus is essentially fully
      formed at stage 58 (approximately 5 weeks). The data reported here will serve as
      ground-based controls for fertilized newt eggs flown on the International
      Microgravity Laboratory-2 Space Shuttle flight, to investigate the influence of
      microgravity on the development of the gravity-sensing organs.

PMID- 7642455
TI  - Development of cochlear potentials in the neonatal gerbil.
AB  - The onset and maturation of hearing was examined in separate groups of sibling
      and nonsibling neonatal Mongolian gerbils (Meriones unguiculatus). Auditory nerve
      compound action potentials (CAP) and cochlear microphonics (CM) were measured at
      the round window, and the endocochlear potential (EP) was recorded at three
      different locations in pups aged 13 to 30 days after birth (DAB) and in 90 day
      old animals. Maturational trends for the three potentials were similar to those
      previously reported for gerbil neonates. However, CAP thresholds continued to
      decrease, and CM and CAP input/output functions and EP continued to increase
      beyond 30 days of age, a time at which many investigators have considered hearing
      in the gerbil to be mature. The EP developed simultaneously throughout the
      cochlea and approached 80 mV by 20 DAB. CAP thresholds showed a highly correlated
      log-linear relationship with EP in groups of nonlittermates and in siblings
      studied at different ages. In contrast, maximum CAP and CM amplitudes increased
      with increasing EP, but did not show significant growth until the EP exceeded 70
      mV.

PMID- 7642456
TI  - The morphogenic features of otoconia during larval development of Cynops
      pyrrhogaster, the Japanese red-bellied newt.
AB  - Otoconia are calcified protein matrices within the gravity-sensing organs of the
      vertebrate vestibular system. Mammalian otoconia are barrel-shaped with triplanar
      facets at each end. Reptilian otoconia are commonly prismatic or fusiform in
      shape. Amphibians have all three otoconial morphologies, barrel-shaped otoconia
      within the utricle, with prismatic and fusiform otoconia in the saccule. Scanning
      electron microscopy revealed a sequential appearance of all three otoconial
      morphologies during larval development of the newt, Cynops pyrrhogaster. The
      first otoconia appear within a single, developing otolith, and some resemble
      adult barrel-shaped otoconia. As the larvae hatch, around stages 39-42, the
      single otolith divides into two anatomically separate regions, the utricle and
      saccule, and both contain otoconia similar to those seen in the single otolith.
      Throughout development, these otoconia may have variable morphologies, with
      serrated surfaces, or circumferential striations with either separated facets or
      adjacent facets in the triplanar end-regions. Small fusiform otoconia occur
      later, at stage 51, and only in the saccule. Prismatic otoconia appear later
      still, at stage 55, and again only in the saccule. Thus, although prismatic
      otoconia are the most numerous in adult newts, it is the last vestibular
      otoconial morphology to be expressed.

PMID- 7642457
TI  - Temperature-dependence of saccular nerve fiber response in the North American
      bullfrog.
AB  - A clinical microwave device was used to heat the head and ear of the North
      American bullfrog in order to observe the temperature dependence of tuning in the
      sacculus, an organ known to possess the capability of electrical resonance in its
      hair cells. In tuning curves derived from reverse correlation analysis with noise
      stimuli, the temperature dependencies of the frequencies of tuning peaks and
      notches typically exhibited Q10s less than 1.1; whereas the frequencies of
      electrical resonances are expected to have Q10s of the order of 1.7. Therefore we
      conclude that electrical resonances are not significantly involved in tuning in
      the bullfrog sacculus.

PMID- 7642458
TI  - Afferent synaptic changes in auditory hair cells during noise-induced temporary
      threshold shift.
AB  - This study presents evidence in support of the hypothesis that one of the sites
      of failure during noise-induced temporary threshold shift (TTS) is the afferent
      synapse between auditory hair cells and auditory nerve fibers. Our results show
      clear evidence indicating changes in the quantity of afferent synapses and the
      morphology of presynaptic structures in the alligator lizard auditory hair cells
      during TTS. In TTS hair cells there are statistically significant decreases in:
      1) the number of afferent synapses, 2) the number of synaptic vesicles at the
      afferent synapses, 3) the size of synaptic bodies, and 4) the packing density of
      synaptic vesicles around the synaptic body. These results suggest that the
      presynaptic components of the afferent synapse reflect the functional state of
      the synapse, and that the reduction of these synapses, both in number and
      component size, contributes to TTS.

PMID- 7642459
TI  - Masker interaural phase and the MLD: effects of conductive hearing loss.
AB  - Sensitivity to binaural signals that were interaurally antiphasic with respect to
      the masking noise was examined as a function of the interaural phase of the
      masking noise, for listeners with normal hearing, and listeners with conductive
      hearing losses. Some of the hearing-impaired listeners were tested both before
      and after middle ear surgery. In agreement with previous findings, the normal
      hearing listeners showed the lowest thresholds when the masking noise had no
      interaural phase shift, with thresholds increasing monotonically as the
      interaural phase of the center frequency of the masker approached +/- 180
      degrees. Although many of the masked threshold functions of the hearing-impaired
      listeners showed significant changes in thresholds as a function of masker
      interaural phase, most of the functions were abnormal in shape, and few showed
      peaks for the interaural masker phase of 0 degrees. Although functions often
      continued to be abnormal after middle ear surgery, a few subjects obtained
      postsurgery functions that were correlated with the average normal function. The
      results indicate that although normal-hearing listeners generally have the lowest
      antiphasic signal threshold for a masker with 0 degrees interaural phase,
      conductively-impaired listeners often do not show a clear minimum for antiphasic
      signal threshold at any particular masker interaural phase.

PMID- 7642460
TI  - Relative importance of personality and general mental ability in managers'
      judgments of applicant qualifications.
AB  - Eighty-four managers who make hiring decisions in 1 of 6 occupations
      representative of J. L. Holland's (1973) 6 job typologies (medical technologist,
      insurance sales agent, carpenter, licensed practical nurse, reporter, and
      secretary) rated 39 hypothetical job applicants on 2 dependent variables,
      hirability and counterproductivity. Applicants were described on the Big Five
      personality factors (Emotional Stability, Extraversion, Openness to Experience,
      Agreeableness, and Conscientiousness) and on general mental ability. Results
      showed that general mental ability and conscientiousness were the most important
      attributes related to applicants' hirability and that Emotional Stability,
      Conscientiousness, and Agreeableness were the most important attributes related
      to counterproductivity. In most respects, these results mirror meta-analytic
      reviews of validity studies, thereby confirming hypotheses.

PMID- 7642461
TI  - Facilitating children's eyewitness recall with the revised cognitive interview.
AB  - Eighty-six 2nd-grade children participated in a Simon says game with an
      unfamiliar adult. The children were subsequently interviewed twice with either a
      standard interview or the revised cognitive interview (CI), once within 3 hr of
      the event and then 2 weeks later. On both the initial interview and the 2-week
      delayed interview, children receiving the revised CI recalled significantly more
      correct information than did children receiving a standard interview. In
      addition, children who were interviewed twice with the revised CI recalled more
      unique accurate facts (M = 25.44) than children who received 2 standard
      interviews (M = 16.75). The CI also elicited more inaccurate facts; however, the
      accuracy rate (proportion of reported facts that were accurate) for the 2 groups
      was equivalent. The research has implications for police and others who interview
      real child victims and witnesses.

PMID- 7642462
TI  - Drug resistance in clinical oncology and hematology. Introduction.

PMID- 7642463
TI  - P-glycoprotein in adult hematologic malignancies.
AB  - The huge discrepancies in the proportion of tumors positive for P-gp observed in
      the literature limit any definite conclusions, except for the urgent need for
      standardized methods to compare results. It is well known by scientists that only
      positive results are published. For this reason, the frequency of P-gp expression
      in leukemia and lymphoma may be overestimated. The role of the MDR phenotype in
      clinical resistance is also not clearly demonstrated, because of the frequent
      association of other markers of bad prognosis on the same subset of cells (CD34,
      CD7 in leukemia). Hematologic malignancies are the most extensively studied
      tumors for drug resistance, and they could be a model for the therapeutic use of
      modifier agents. Many clinical trials are now ongoing in myeloma, acute leukemia,
      and lymphoma, with new modifier agents. The standardization of methods for P-gp,
      permitting large multicentric studies, and the results of randomized studies with
      modifier agents will help us know if mdr1 gene overexpression is of clinical
      importance in hematologic malignancies.

PMID- 7642464
TI  - P-glycoprotein in adult solid tumors. Expression and prognostic significance.
AB  - Several potential mechanisms of chemotherapy resistance have been identified in
      adult solid tumors. The multidrug resistance (MDR) phenotype is one mechanism by
      which tumors may simultaneously develop resistance to multiple chemotherapeutic
      agents and is associated with P-glycoprotein expression. In this article, the
      authors examine the literature and summarize the various techniques used to
      measure MDR1 gene expression, patterns of expression in adult solid tumors.

PMID- 7642465
TI  - Multidrug resistance in pediatric malignancies.
AB  - PURPOSE: Increased expression of P-glycoprotein is an important cause of
      multidrug resistance in tumor cell lines in vitro. Whether this mechanism is
      equally relevant as a cause of clinical chemoresistance has not been established
      and is currently being investigated. This review has examined the
      immunohistochemical and molecular biologic tools suitable for assessing P
      glycoprotein expression in patient samples and methodologic issues important for
      evaluating the results of clinical studies. Current evidence that supports a role
      for P-glycoprotein in limiting the efficacy of cancer chemotherapy has been
      reviewed. DESIGN: Malignancies that have been successfully treated by
      chemotherapeutic substrates of P-glycoprotein, in which a proportion of patients
      still fail therapy, may be the most useful models for determining whether this
      drug efflux transporter is a clinically relevant cause of chemoresistance.
      RESULTS: Studies of acute myelogenous leukemia, lymphoma, and myeloma in adults
      have so far provided the best evidence for a relevant role for P-glycoprotein as
      a cause of clinical multidrug resistance. A similar strong association has been
      observed between the expression of P-glycoprotein and outcome of treatment in
      certain malignancies in children, such as neuroblastoma, rhabdomyosarcoma, and
      acute lymphoblastic leukemia. Some apparent controversies related to this issue
      of clinical relevance may be explained by the differences in P-glycoprotein
      detection techniques, methodology, and experimental designs used in different
      studies. Because several clinical trials have already been initiated to determine
      whether pharmacologic chemosensitization improves the outcome of chemotherapy in
      certain malignancies, the successful verification of multidrug resistance
      limiting the cure rates of these tumors becomes a more critical issue, and
      identification of those patients with lower levels of P-glycoprotein expression
      early in the course of their disease, when they are most likely to benefit from
      multidrug resistance reversal, has assumed an even greater relevance. CONCLUSION:
      The clinical relevance of the multidrug resistance P-glycoprotein may ultimately
      be confirmed by the successful prevention of chemotherapy failure by
      chemosensitizers that specifically reverse this drug efflux mechanism.

PMID- 7642466
TI  - MDR expression in normal tissues. Pharmacologic implications for the clinical use
      of P-glycoprotein inhibitors.
AB  - The use of drugs such as calcium channel blocker agents and cyclosporins as an
      approach to reverse the MDR phenomenon in controlled clinical trials has
      demonstrated the combination of these agents to markedly alter the
      pharmacokinetics of a number of cytotoxins associated with MDR characteristics,
      including doxorubicin, etoposide, paclitaxel, and vincristine. These effects are
      likely to be the combined effects of MDR modulators to produce decreased
      metabolism of the cytotoxins via the cytochrome P-450 system and decreased
      biliary and renal transport/excretion. It still remains to be established if the
      mdr1 gene is a primary drug transporter in these organs. Specificity of MDR
      modulators for drug metabolism and excretion requires further study, because some
      modulators of MDR, such as progesterone, have shown no interaction with
      cytotoxins (that is, doxorubicin) in clinical trials. Trials to date have
      indicated many modulators of MDR at doses which achieve concentrations that
      reverse MDR in vitro may lead to alterations of tissue function and enhance
      toxicity to normal tissue. In vitro data suggest many MDR modulators will enhance
      hematologic toxicity, beyond that predicted by the increased exposure from
      pharmacokinetic effects. When these interactions occur, it has been necessary to
      reduce the dosages of the cytotoxins in the range of 40% to 50% in most trials,
      if similar normal tissue toxicity--that is, myelosuppression or neuropathy--is
      expected. However, these empiric dose modifications in the absence of concurrent
      pharmacokinetic monitoring could compromise tumor exposure. Other toxicities that
      may be enhanced during the use of MDR modulators are nausea and vomiting,
      consistent with the hypothesis for a disruption of blood-brain barrier function,
      and augmented vinca alkaloid-associated autonomic and peripheral neuropathies.
      Future laboratory studies should define more effective modulators and the role of
      the mdr1 gene in normal tissue toxicology. These trials should focus on defining
      the pharmacokinetic and toxicologic interactions between the modulators and
      antineoplastic agents and formulate dosing guidelines for their testing in
      pivotal phase II and controlled phase III trials.

PMID- 7642467
TI  - Modulators of multidrug resistance. Preclinical studies.
AB  - The study of the cellular, biochemical, and molecular biology and pharmacology of
      MDR has provided one of the most active and exciting areas within cancer research
      for translation into potential clinical benefit. Although convincing evidence for
      the functional role of P-gp in mediating clinical drug resistance in humans
      remains scant, studies of the clinical expression of P-gp and trials of
      chemosensitizers with cancer chemotherapy suggest "resistance modification"
      strategies may be effective in some tumors with intrinsic or acquired drug
      resistance. However, even if P-gp-associated MDR proves to be a relevant and
      reversible cause of clinical drug resistance, numerous problems remain to be
      solved before effective clinical chemosensitization may be achieved. Such factors
      as absorption, distribution, and metabolism, the effect of chemosensitizers on
      chemotherapeutic drug clearance, toxicity to normal tissues expressing P-gp, and
      the most efficacious modulator regimens all remain to be defined in vivo.
      Clearly, the identification of more specific, more potent, and less clinically
      toxic chemosensitizers for clinical use remains critical to the possible success
      of this approach. However, the finding that a number of pharmacologic agents can
      antagonize a well-characterized form of experimental drug resistance provides
      promise for potential clinical applications. Further study of chemosensitizers in
      humans and the rational design of novel chemosensitizers with improved activity
      should define the importance of MDR to clinically resistant cancer.

PMID- 7642468
TI  - Clinical studies with modulators of multidrug resistance.
AB  - Improved understanding of the mechanisms underlying chemotherapeutic failure has
      led to new strategies to circumvent drug resistance. Expression of the multidrug
      transporter, P-glycoprotein (P-gp), is likely to be a significant mechanism
      contributing to the clinical resistance of some cancers to chemotherapy. Phase I
      trials of currently available MDR modulators have yielded important pharmacologic
      principles pertaining to normal tissue P-gp function and its influence on the
      disposition of MDR-related anticancer drugs. Currently available P-glycoprotein
      inhibitors lack the potency to completely reverse the MDR phenotype at clinically
      achievable concentrations. Despite this, encouraging clinical results have been
      obtained in the hematolymphoid malignancies. As these more potent modulators
      become available, careful characterization of pharmacologic interactions with MDR
      related cytotoxins will be critical to the rational design of Phase II and III
      studies that will ultimately test the efficacy of MDR modulation.

PMID- 7642469
TI  - Modulation of glutathione and related enzymes in reversal of resistance to
      anticancer drugs.
AB  - Eukaryotic cells have evolved several mechanisms to protect cellular
      constituents, especially DNA, from highly reactive molecules entering from
      without. The greater affinity of electrophiles for thiol groups than for hydroxyl
      or amine groups provides a teleologic rationale that the availability of high
      concentrations of thiol could be protective of these other important entities.
      The major intracellular nonprotein thiol is the tripeptide glutathione.

PMID- 7642470
TI  - Clinical resistance to antimetabolites.
AB  - Antimetabolites are rational agents with specific S-phase and enzyme targets. Low
      levels of target enzymes in tumors are associated with innate drug sensitivity,
      and the general requirement for transport and metabolic activation of
      antimetabolites creates several loci of acquired drug resistance. Pharmacodynamic
      studies of TS inhibition after fluoropyrimidines clearly can predict for tumor
      sensitivity and response to fluoropyrimidine-based therapy or identify factors
      related to resistance, and ara-dCTP levels in leukemic cells can be useful for
      refined dosing of araC. Powerful new DHFR and TS directed agents are in advanced
      levels of clinical evaluation, and purine analogues directed against adenosine
      deaminase are newly available for treatment of indolent lymphomas. Progress in
      analysis of tumors, such as PCR techniques to study gene expression or
      immunostaining of target enzymes, offer increasing promise for individualization
      of patient selection. Increased experience with biochemical modulators, including
      biologic response modifiers, has opened the possibility for selective attack on
      specific mechanisms of drug resistance. Sophisticated pharmacokinetic modeling
      and pharmacogenetic testing of metabolic phenotypes can now be done to achieve
      optimal dosing with less risk of toxicity. Considerations of ultimate genetic
      mechanisms of antimetabolite effects, especially by programmed cell death, and
      relationships to mechanisms of cell cycle regulation offer exciting rationales
      for future drug development.

PMID- 7642471
TI  - Preclinical and clinical experience with cisplatin resistance.
AB  - Despite the general lack of clinical evidence supporting the preclinical data,
      there have been many attempts to overcome cisplatin resistance in clinical
      situations. These efforts have focused on both the proposed mechanisms of
      resistance as well as novel approaches to renew efficacy. In this article, the
      authors summarize the available clinical studies that have intentionally or
      serendipitously uncovered modulators of cisplatin sensitivity.

PMID- 7642472
TI  - O6-alkylguanine-DNA alkyltransferase. A target for the modulation of drug
      resistance.
AB  - The DNA repair protein, O6-alkylguanine DNA alkyltransferase, is a major
      contributor to the resistance to the nitrosourea, triazine, and tetrazine class
      of alkylating agents. Many tumor cells and primary tumor samples contain high
      levels of this protein, although a great deal of heterogeneity exists between and
      within tumors. Inhibition of the alkyl-transferase by O6-benzylguanine results in
      significant potentiation of the cytotoxic effects of these chemotherapeutic
      agents, generating responses in human tumor xenografts that are completely
      resistant to nitrosoureas alone. These studies may rekindle the interest in the
      nitrosourea class of alkylating agents and stimulate the search for inhibitors of
      other mechanisms of chemotherapy resistance.

PMID- 7642473
TI  - Bcl-2: prevention of apoptosis as a mechanism of drug resistance.
AB  - Programmed cell death (also known as apoptosis) plays an essential role in tissue
      homeostasis, where it ensures that new cell production in the body is offset by a
      commensurate rate of cell loss. Defects in the genetic pathway that regulate the
      cell death process can figure prominently in the origins of cancer and also in
      problems with cancer treatment. Eventually, it may be possible to develop novel
      treatments for cancer that specifically seek to modulate the physiologic cell
      death pathway as opposed to nearly all currently available drugs, which are
      intended to interfere with some aspect of the cell division cycle.

PMID- 7642475
TI  - Getting EMS into the emergency room.

PMID- 7642474
TI  - Physiologic mechanisms of therapeutic resistance. Blood flow and hypoxia.
AB  - The tools now are available to characterize oxygenation/hypoxia in the clinic.
      The clinical investigations conducted thus far have shown that significant
      regions of hypoxia exist in solid tumors in patients. Of the various strategies
      developed in the laboratory for reducing (or eliminating) hypoxia in tumors, the
      intravenous administration of nontoxic oxygen-carrying materials is probably the
      most generally applicable in a clinical setting.

PMID- 7642476
TI  - Bicycle/automobile accidents in Arkansas 1991-1993.
AB  - Bicycling is frequently recommended as a form of aerobic exercise to reduce the
      risk of cardiovascular events, yet it is not without safety risks. The recent
      accidental death of locally-known cyclist has raised safety concerns of
      recreational cycling on Arkansas roads. This article summarizes cycling accident
      statistics obtained from the Arkansas State Highway and Transportation Department
      for a three year period.

PMID- 7642477
TI  - Common bacterial sexually transmitted diseases in pregnancy.

PMID- 7642478
TI  - Post cesarean section death.

PMID- 7642479
TI  - Thrombolytic therapy in patients with an abnormality of blood coagulation.

PMID- 7642481
TI  - Radiological case of the month. Post-traumatic degenerative change of the
      cervical spine.

PMID- 7642480
TI  - Tickborne diseases in Arkansas.

PMID- 7642482
TI  - Disulfide bond formation and secretion of Escherichia coli heat-stable
      enterotoxin II.
AB  - The Escherichia coli heat-stable enterotoxin II (STII) is a typical extracellular
      toxin consisting of 48 amino acid residues, of which 4 are cysteine. There are
      two disulfide bonds, one between Cys-10 and Cys-48 and one between Cys-21 and Cys
      36. We examined the involvement of DsbA in the formation of the disulfide bonds
      of STII and the role of each in the secretion of STII. A dsbA mutant was
      transformed with a plasmid harboring the STII gene, and STII was not detected
      either in the cells or in the culture supernatant. Reducing the level of STII
      brought about the dsbA mutation restored by introducing the wild-type dsbA gene
      into the mutant strain. These results showed that DsbA is involved in forming the
      disulfide bonds of STII and that STII without these disulfide bonds is degraded
      during secretion. We substituted these four cysteine residues in vivo by
      oligonucleotide-directed site-specific mutagenesis. The amino acid sequence of
      the purified STII (C48S) and pulse-chase studies revealed that two intermolecular
      disulfide bonds must be formed to be efficiently secreted and that cleavage
      between amino acid residues 14 and 15 is probably the first step in the
      proteolytic degradation of STII.

PMID- 7642483
TI  - Aerobic inactivation of fumarate reductase from Escherichia coli by mutation of
      the [3Fe-4S]-quinone binding domain.
AB  - Fumarate reductase from Escherichia coli functions both as an anaerobic fumarate
      reductase and as an aerobic succinate dehydrogenase. A site-directed mutation of
      E. coli fumarate reductase in which FrdB Pro-159 was replaced with a glutamine or
      histidine residue was constructed and overexpressed in a strain of E. coli
      lacking a functional copy of the fumarate reductase or succinate dehydrogenase
      complex. The consequences of these mutations on bacterial growth, assembly of the
      enzyme complex, and enzymatic activity were investigated. Both mutations were
      found to have no effect on anaerobic bacterial growth or on the ability of the
      enzyme to reduce fumarate compared with the wild-type enzyme. The FrdB Pro-159-to
      histidine substitution was normal in its ability to oxidize succinate. In
      contrast, however, the FrdB Pro-159-to-Gln substitution was found to inhibit
      aerobic growth of E. coli under conditions requiring a functional succinate
      dehydrogenase, and furthermore, the aerobic activity of the enzyme was severely
      inhibited upon incubation in the presence of its substrate, succinate. This
      inactivation could be prevented by incubating the mutant enzyme complex in an
      anaerobic environment, separating the catalytic subunits of the fumarate
      reductase complex from their membrane anchors, or blocking the transfer of
      electrons from the enzyme to quinones. The results of these studies suggest that
      the succinate-induced inactivation occurs by the production of hydroxyl radicals
      generated by a Fenton-type reaction following introduction of this mutation into
      the [3Fe-4S] binding domain. Additional evidence shows that the substrate-induced
      inactivation requires quinones, which are the membrane-bound electron acceptors
      and donors for the succinate dehydrogenase and fumarate reductase activities.
      These data suggest that the [3Fe-4S] cluster is intimately associated with one of
      the quinone binding sites found n fumarate reductase and succinate dehydrogenase.

PMID- 7642484
TI  - Mutation of the Ser2 codon of the light-harvesting B870 alpha polypeptide of
      Rhodobacter capsulatus partially suppresses the pufX phenotype.
AB  - The exact function of the pufX gene product of Rhodobacter capsulatus is
      uncertain, but deletion of the pufX gene renders cells incapable of phototrophic
      growth on a minimal medium, and photosynthetic electron transfer is impaired in
      vitro. However, suppressor mutants that are able to grow phototropically are
      readily isolated. Two such suppressor mutants were characterized as to their
      phototrophic growth properties, their fluorescence at different incident light
      intensities, the integrity of their chromatophores, and their abilities to
      generate a transmembrane potential. We found that the photosynthetic apparatus in
      the suppressor mutants was less stable than that of the pseudo-wild-type and
      primary mutant strains and that the suppressor mutants used light energy less
      efficiently than the pseudo-wild-type strain. Therefore, the suppressor strains
      are more precisely designated partial suppressor mutants. The locations and
      sequences of the suppressor mutations were determined, and both were found to
      change the second codon of the pufA gene. It is hypothesized that the serine
      residue specified by this codon is important in interactions between the B870
      alpha protein and other membrane-bound polypeptides and that suppressor mutations
      at this position partially compensate for loss of the PufX protein. A model is
      proposed for the function of the PufX protein.

PMID- 7642485
TI  - The sapA promoter from Streptomyces coelicolor requires activation sites and
      initiator-like sequences but No -10 or -35 sequences.
AB  - The Streptomyces coelicolor sapA gene encodes a spore coat protein. The sapA
      promoter is regulated developmentally, with maximal expression occurring in
      aerial hyphae at a late stage of colonial development. The DNA sequences upstream
      from the transcription start point do not appear to fall into a previously
      described promoter class. One (or more) putative activation site, required for
      full activity, is eliminated when 5' deletions extend to between -178 and -72
      bases upstream from the transcription start point. In addition, a downstream
      activation site is destroyed by removing sequences between positions +40 and
      +120, relative to the transcription start point, in the absence of an intact
      upstream region. However, temporal regulation of transcription initiation over
      the course of the life cycle is maintained faithfully in the absence of these
      elements, even in the smallest 18-bp sapAp fragment containing sequences from
      positions -8 to +10. Site-specific mutations around the transcriptional start
      points shift the timing of sapA expression to an earlier stage in the
      developmental cycle. These results sugges that a novel mechanism may be involved
      in Streptomyces late gene expression.

PMID- 7642486
TI  - appA, a novel gene encoding a trans-acting factor involved in the regulation of
      photosynthesis gene expression in Rhodobacter sphaeroides 2.4.1.
AB  - A new gene, the product of which is involved in the regulation of photosynthesis
      gene expression in the anoxygenic photosynthetic bacterium Rhodobacter
      sphaeroides 2.4.1, has been identified. The isolation of this gene, designated
      appA (activation of photopigment and puc expression), was based on its ability,
      when provided in extra copies, to partially suppress mutations in the two
      component PrrB-PrrA regulatory system. The presence of extra copies of the appA
      gene in either prrB, prrA, or wild-type strains resulted in an activation of
      puc::lacZ expression under aerobic conditions. Constructed AppA null mutants did
      not grow photosynthetically and were impaired in the synthesis of both
      bacteriochlorophyll and carotenoids, as well as the structural proteins of the
      photosynthetic spectral complexes. When grown anaerobically in the dark, these
      mutants accumulated bacteriochlorophyll precursors. The expression of lacZ
      fusions to several photosynthesis genes and operons, including puc, puf, and
      bchF, was decreased in the AppA mutant strains in comparison with the wild type.
      To examine the role of AppA involvement in bacteriochlorophyll biosynthesis, we
      inactivated an early gene, bchE, of the bacteriochlorophyll pathway in both wild
      type and AppA- mutant backgrounds. The double mutant, AppA- BchE-, was found to
      be severely impaired in photosynthesis gene expression, similar to the AppA-
      BchE+ mutant and in contrast to the AppA+ BchE- mutant. This result indicated
      that AppA is more likely involved in the regulation of expression of the bch
      genes than in the biosynthetic pathway per se. The appA gene was sequenced and
      appears to encode a protein of 450 amino acids with no obvious homology to known
      proteins.

PMID- 7642487
TI  - The Bacillus subtilis SinR protein is a repressor of the key sporulation gene
      spo0A.
AB  - SinR is a pleiotropic DNA binding protein that is essential for the late-growth
      processes of competence and motility in Bacillus subtilis and is also a repressor
      of others, e.g., sporulation and subtilisin synthesis. In this report, we show
      that SinR, in addition to being an inhibitor of sporulation stage II gene
      expression, is a repressor of the key early sporulation gene spo0A. The
      sporulation-specific rise in spo0A expression at time zero is absent in a SinR
      overproducing strain and is much higher than normal in strains with a disrupted
      sinR gene. This effect is direct, since SinR binds specifically to spo0A in
      vitro, in a region overlapping the -10 region of the sporulation-specific Ps
      promoter that is recognized by E-sigma H polymerase. Methyl interference and site
      directed mutagenesis studies have identified guanine residues that are important
      for SinR recognition of this DNA sequence. Finally, we present evidence that SinR
      controls sporulation through several independent genes, i.e., sp0A, spoIIA, and
      possibly spoIIG and spoIIE.

PMID- 7642488
TI  - Fur regulon of Salmonella typhimurium: identification of new iron-regulated
      genes.
AB  - In order to identify genes belonging to the Fur regulon of Salmonella
      typhimurium, a bank of 10,000 independent S. typhimurium MudJ insertion mutants
      was screened for lacZ fusions regulated by the iron response regulator Fur. In
      parallel, a plasmid gene bank of S. typhimurium consisting of 10,000 independent
      clones was screened for Fur-regulated promoters or iron binding proteins by the
      Fur titration assay (FURTA). Fur-regulated MudJ insertions and Fur-regulated
      promoters were mapped. In addition, iron-regulated promoter activities of
      transcriptional fusions from MudJ insertions and FURTA-positive clones were
      quantified. The nucleotide sequences of 11 FURTA-positive plasmids and of short
      fragments of DNA flanking three MudJ insertions were determined. By these methods
      we identified 14 Fur-regulated genes of S. typhimurium. For 11 of these genes,
      Fur-regulated homologs have been described in Escherichia coli or Yersinia
      enterocolitica, including fhuA,fhuB,fepA,fes,fepD,p43,entB,fur ,foxA,hemP, and
      fhuE. In addition, we identified three genes with homologs in other bacteria
      which have not previously been shown to be Fur regulated.

PMID- 7642489
TI  - An early A-signal-dependent gene in Myxococcus xanthus has a sigma 54-like
      promoter.
AB  - A-signaling plays an essential role in the early stages of Myxococcus xanthus
      fruiting body development. Expression of the 452I gene, which is regulated at the
      level of RNA accumulation, depends on starvation and on A-signaling. To identify
      the cis-acting regulatory elements which allow gene 4521 to respond to the
      nutritional and A-factor signals, the 4521 transcription start site was mapped.
      The region just upstream of the start site showed sequence similarity to the
      sigma 54 family of promoters and to the developmentally regulated mbhA promoter
      of M. xanthus. A mutational analysis of this region established that the bases
      which were conserved between the sigma 54 consensus, mbhA, and 4521 promoters
      were also important for 4521 promoter activity. Changes which altered the spacing
      between two conserved regions centered around positions -14 and -24 abolished
      promoter activity. In contrast, mutations in a putative -10 region for a sigma 70
      like promoter had little effect on expression of 4521. Despite their similar
      promoter regions, the regulation of the 4521 and mbhA genes was shown to differ
      with respect to timing of expression and requirement for a solid surface and
      extracellular signals. This suggests a model in which different activator
      proteins may be responsible for regulating expression of these two genes.

PMID- 7642490
TI  - Identification of the minimum regulatory region of a Myxococcus xanthus A-signal
      dependent developmental gene.
AB  - Developmental expression of the Myxococcus xanthus gene 4521 requires
      extracellular A-signal. This signal is generated in response to nutrient
      limitation and functions in cell density sensing. To identify the upstream limit
      of the minimum region required in vivo for A-signal-dependent 4521 expression, a
      5' deletion analysis of the 4521 regulatory region was performed. A new vector,
      pHBK280, was designed to facilitate this analysis. This vector creates tandem
      copies of the 4521 gene in the M. xanthus chromosome, such that the regulatory
      region to be tested is upstream of a single copy of the lacZ reporter gene. The
      5' deletion analysis revealed that at most, 146 bp of DNA upstream of the
      transcription start site (TSS) was required for full developmental expression of
      4521. Basal expression levels were observed with constructions containing 90 bp
      of DNA upstream of the TSS. In vitro gel retardation assays revealed that DNA
      fragments with 5' ends of 146 and 125 bp upstream of the TSS and a common 3' end
      of +24 bp were retarded in their mobility after incubation with all of the M.
      xanthus developmental crude cell extracts tested. In contrast, a fragment
      starting at 90 bp upstream of the TSS and ending at +24 bp was not retarded in
      its mobility after incubation with the same cell extracts. These in vivo and in
      vitro data suggest that cis-acting elements located between 146 and 90 bp
      upstream of the TSS serve as binding sites for one or more trans-acting
      regulatory factors required for 4521 developmental expression.

PMID- 7642491
TI  - Specificity of peptide transport systems in Lactococcus lactis: evidence for a
      third system which transports hydrophobic di- and tripeptides.
AB  - A proton motive force-driven di-tripeptide carrier protein (DtpT) and an ATP
      dependent oligopeptide transport system (Opp) have been described for Lactococcus
      lactis MG1363. Using genetically well-defined mutants in which dtpT and/or opp
      were inactivated, we have now established the presence of a third peptide
      transport system (DtpP) in L. lactis. The specificity of DtpP partially overlaps
      that of DtpT. DtpP transports preferentially di- and tripeptides that are
      composed of hydrophobic (branched-chain amino acid) residues, whereas DtpT has a
      higher specificity for more-hydrophilic and charged peptides. The toxic dipeptide
      L-phenylalanyl-beta-chloro-L-alanine has been used to select for a di-tripeptide
      transport-negative mutant with the delta dtpT strain as a genetic background.
      This mutant is unable to transport di- and tripeptides but still shows uptake of
      amino acids and oligopeptides. The DtpP system is induced in the presence of di-
      and tripeptides containing branched-chain amino acids. The use of ionophores and
      metabolic inhibitors suggests that, similar to Opp, DtpP-mediated peptide
      transport is driven by ATP or a related energy-rich phosphorylated intermediate.

PMID- 7642492
TI  - Identification and characterization of a locus which regulates multiple functions
      in Pseudomonas tolaasii, the cause of brown blotch disease of Agaricus bisporus.
AB  - Pseudomonas tolaasii, the causal agent of brown blotch disease of Agaricus
      bisporus, spontaneously gives rise to morphologically distinct stable sectors,
      referred to as the phenotypic variant form, at the margins of the wild-type
      colonies. The phenotypic variant form is nonpathogenic and differs from the wild
      type in a range of biochemical and physiological characteristics. A genomic
      cosmid clone (pSISG29) from a wild-type P. tolaasii library was shown to be
      capable of restoring a range of characteristics of the phenotypic variant to
      those of the wild-type form, when present in trans. Subcloning and saturation
      mutagenesis analysis with Tn5lacZ localized a 3.0-kb region from pSISG29,
      designated the pheN locus, required for complementation of the phenotypic variant
      to the wild-type form. Marker exchange of the Tn5lacZ-mutagenized copy of the
      pheN locus into the wild-type strain demonstrated that a functional copy of the
      pheN gene is required to maintain the wild-type pathogenic phenotype and that
      loss of the pheN gene or its function results in conversion of the wild-type form
      to the phenotypic variant form. The pheN locus contained a 2,727-bp open reading
      frame encoding an 83-kDa protein. The predicted amino acid sequence of the PheN
      protein showed homology to the sensor and regulator domains of the conserved
      family of two component bacterial sensor regulator proteins. Southern
      hybridization analysis of pheN genes from the wild type and the phenotypic
      variant form revealed that DNA rearrangement occurs within the pheN locus during
      phenotypic variation. Analysis of pheN expression with a pheN::lacZ fusion
      demonstrated that expression is regulated by environmental factors. These results
      are related to a model for control for phenotypic variation in P. tolaasii.

PMID- 7642493
TI  - Sulfonamide resistance in Neisseria meningitidis as defined by site-directed
      mutagenesis could have its origin in other species.
AB  - Sulfonamide resistance in Neisseria meningitidis is mediated by altered forms of
      the chromosomal gene for the drug target enzyme dihydropteroate synthase.
      Sulfonamides have been used for decades both for prophylaxis and the treatment of
      meningococcal disease, and resistance is common. Two types of resistance
      determinants have been identified, and regions important for drug
      insusceptibility to the corresponding enzyme have been defined by site-directed
      mutagenesis. Both types of resistance traits have spread among strains of N.
      meningitidis of different serogroups and serotypes, and the large differences at
      the nucleotide level in a comparison of the resistance genes with the dhps genes
      of susceptible meningococci indicate the origin of one or maybe both types in
      other Neisseria species. One sulfonamide-sensitive strain of N. meningitidis was
      found to have a mosaic dhps gene with a central part identical to the
      corresponding part of a gonococcal strain. This observation supports the idea of
      an interspecies transfer of genetic material in Neisseria species as a mechanism
      for the development of chromosomally mediated resistance.

PMID- 7642494
TI  - Identification of transcriptional start sites and the role of ppGpp in the
      expression of rpoS, the structural gene for the sigma S subunit of RNA polymerase
      in Escherichia coli.
AB  - rpoS is the structural gene for the sigma S subunit of RNA polymerase which
      controls the expression of a large number of genes in Escherichia coli that are
      induced during entry into stationary phase or in response to increased medium
      osmolarity. Using a combination of primer extension experiments and a 5' deletion
      analysis of the region upstream of rpoS, we show that rpoS transcription is
      mainly driven by a single promoter (rpoSp1) located within the nlpD gene upstream
      of rpoS (the two relatively weak nlpD promoters contribute to the low level of
      rpoS expression during early exponential phase). In addition, we demonstrate that
      the expression of both transcriptional and translational rpoS::lacZ fusions as
      well as the level of rpoS mRNA originating at rpoSp1 is strongly reduced in ppGpp
      deficient relA spoT mutants. However, experiments with the 5' deletion constructs
      indicate that a lack of ppGpp does affect transcriptional elongation rather than
      initiation.

PMID- 7642495
TI  - Two genes involved in the phase-variable phi C31 resistance mechanism of
      Streptomyces coelicolor A3(2).
AB  - The phage growth limitation (Pgl) system of Streptomyces coelicolor confers
      resistance to phi C31 and its homoimmune phages. The positions of the pgl genes
      within a 16-kb clone of S. coelicolor DNA were defined by subcloning, insertional
      inactivation, and deletion mapping. Nucleotide sequencing and functional analysis
      identified two genes, pglY and pglZ, required for the Pgl+ (phage-resistant)
      phenotype. pglY and pglZ, which may be translationally coupled, are predicted to
      encode proteins with M(r)S of 141,000 and 104,000, respectively. Neither protein
      shows significant similarity to other known proteins, but PglY has a putative
      ATP/GTP binding motif. The pglY and pglZ genes are cotranscribed from a single
      promoter which appears to be constitutive and is not induced by phage infection.

PMID- 7642496
TI  - Glycine betaine uptake after hyperosmotic shift in Corynebacterium glutamicum.
AB  - Osmoregulatory uptake of glycine betaine in whole cells of Corynebacterium
      glutamicum ATCC 13032 (wild type) was studied. The cells actively take up glycine
      betaine when they are osmotically shocked. The total accumulation and uptake rate
      were dependent on the osmotic strength of the medium. Kinetic analysis revealed a
      high-affinity transport system (Km, 8.6 +/- 0.4 microM) with high maximum
      velocity (110 nmol.min-1.mg [dry weight]-1). Glycine betaine functioned as a
      compatible solute when added to the medium and allowed growth at an otherwise
      inhibitory osmotic strength of 1.5 M NaCl. Proline and ectoine could also be used
      as osmoprotectants. Glycine betaine is neither synthesized nor metabolized by C.
      glutamicum. The glycine betaine transport system is constitutively expressed at a
      basal level of activity. It can be induced up to eightfold by osmotic stress and
      is strongly regulated at the level of activity. The transport system is highly
      specific and has its pH optimum in the slightly alkaline range at about pH 8. The
      uptake of the zwitterionic glycine betaine is mediated by a secondary symport
      system coupled to cotransport of at least two Na+ ions. It is thus driven both by
      the membrane potential and the Na+ gradient. An extremely high accumulation
      (internal/external) ratio of up to 4 x 10(6) was measured, which represents the
      highest accumulation ratio observed for any transport system.

PMID- 7642497
TI  - Modulation of flagellar expression in Escherichia coli by acetyl phosphate and
      the osmoregulator OmpR.
AB  - During the search for unknown factors involved in motility, we have found that
      expression of the flagellar master operon flhDC is affected by mutations of the
      pta and ackA genes, encoding phosphotransacetylase and acetate kinase,
      respectively (S. Shin, J. Sheen, and C. Park, Korean J. Microbiol. 31:504-511,
      1993). Here we describe results showing that this effect is modulated by
      externally added acetate, except when both pta and ackA are mutated, suggesting
      the role of acetyl phosphate, an intermediate of acetate metabolism, as a
      regulatory effector. Furthermore, the following evidence indicates that the
      phosphorylation of OmpR, a trans factor for osmoregulation, regulates flagellar
      expression. First, in a strain lacking ompR, the expression of flhDC is no longer
      responsive to a change in the level of acetyl phosphate. Second, an increase in
      medium osmolarity does not decrease flhDC expression in an ompR mutant. It is
      known that such an increase normally enhances OmpR phosphorylation. Third, OmpR
      protein binds to the DNA fragment containing the flhDC promoter, and its affinity
      is increased with phosphorylation by acetyl phosphate. DNase I footprinting
      revealed the regions of the flhDC promoter protected by OmpR in the presence or
      absence of phosphorylation. Therefore, we propose that the phosphorylated OmpR,
      generated by either osmolarity change or the internal level of acetyl phosphate,
      negatively regulates the expression of flagella.

PMID- 7642498
TI  - H-NS regulation of virulence gene expression in enteroinvasive Escherichia coli
      harboring the virulence plasmid integrated into the host chromosome.
AB  - We have previously shown that integration of the virulence plasmid pINV into the
      chromosome of enteroinvasive Escherichia coli and of Shigella flexneri makes
      these strains noninvasive (C. Zagaglia, M. Casalino, B. Colonna, C. Conti, A.
      Calconi, and M. Nicoletti, Infect. Immun. 59:792-799, 1991). In this work, we
      have studied the transcription of the virulence regulatory genes virB, virF, and
      hns (virR) in wild-type enteroinvasive E. coli HN280 and in its pINV-integrated
      derivative HN280/32. While transcription of virF and of hns is not affected by
      pINV integration, transcription of virB is severely reduced even if integration
      does not occur within the virB locus. This indicates that VirF cannot activate
      virB transcription when pINV is integrated, and this lack of expression accounts
      for the noninvasive phenotype of HN280/32. Virulence gene expression in strains
      HN280 and HN280/32, as well as in derivatives harboring a mxiC::lacZ operon
      fusion either on the autonomously replicating pINV or on the integrated pINV, was
      studied. The effect of the introduction of plasmids carrying virB (pBNI) or virF
      (pHW745 and pMYSH6504), and of a delta hns deletion, in the different strains was
      evaluated by measuring beta-galactosidase activity, virB transcription, and virB
      regulated virulence phenotypes like synthesis of Ipa proteins, contact-mediated
      hemolysis, and capacity to invade HeLa cells. The introduction of pBN1 or of the
      delta hns deletion in pINV-integrated strains induces temperature-regulated
      expression or temperature-independent expression, respectively, of beta
      galactosidase activity and of all virulence phenotypes, while an increase in virF
      gene dosage does not, in spite of a high-level induction of virB transcription.
      Moreover, a wild-type hns gene placed in trans fully reversed the induction of
      beta-galactosidase activity due to the delta hns deletion. These results indicate
      that virB transcription is negatively regulated by H-NS both at 30 and at 37
      degrees C in pINV-integrated strains and that there is also a dose-dependent
      effect of VirF on virB transcription. The negative effect of H-NS on virB
      transcription at the permissive temperature of 37 degrees C could be due to
      changes in the DNA topology occurring upon pINV integration that favor more
      stable binding of H-NS to the virB promoter DNA region. At 30 degrees C, the
      introduction of the high-copy-number plasmid pMYSH6504 (but not of the low-copy
      number pHW745) or of the deltahns deletion induces, in strains harboring an
      autonomously replicating pINV, beta-galactosidase activity, virB transcription,
      and expression of the virulence phenotypes, indicating that, as for HN280/32, the
      increase in virF gene dosage overcomes the negative regulatory effect of H-NS on
      virB transcription. Moreover, we have found that virF transcription is finely
      modulated by temperature and, with E. coli K-12 strains containing a virF-lacZ
      gene fusion, by H-NS. This leads us to speculate that, in enteroinvasive
      bacteria, the level of Virf inside the cell controls the temperature-regulated
      expression of invasion genes.

PMID- 7642499
TI  - Catabolite-mediated mutations in alternate toluene degradative pathways in
      Pseudomonas putida.
AB  - Pseudomonas putida 54g grew on mineral salts with toluene and exhibited catechol
      2,3-dioxygenase (C23O) activity, indicating a meta pathway. After 10 to 15 days
      on toluene, nondegrading (Tol-) variants approached nearly 10% of total CFU.
      Auxotrophs were not detected among variants, suggesting selective loss of
      catabolic function(s). Variant formation was substrate dependent, since Tol-
      cells were observed on neither ethylbenzene, glucose, nor peptone-based media nor
      when toluene catabolism was suppressed by glucose. Unlike wild-type cells,
      variants did not grow on gasoline, toluene, benzene, ethylbenzene, benzoate, or
      catechol, suggesting loss of meta pathway function. Catabolic and C23O activities
      were restored to variants via transfer of a 78-mDa TOL-like plasmid from a wild
      type Tol+ donor. Tests for reversion of variants to Tol+ were uniformly negative,
      suggesting possible delection or excision of catabolic genes. Deletions were
      confirmed in some variants by failure to hybridize with a DNA probe specific for
      the xylE gene encoding C23O. Cells grown on benzoate remained Tol+ but were C23O-
      and contained a plasmid of reduced size or were plasmid free, suggesting an
      alternate chromosomal catabolic pathway, also defective in variants. Cells
      exposed to benzyl alcohol, the initial oxidation product of toluene, accumulated
      > 13% variants in 5 days, even when cell division was repressed by nitrogen
      deprivation to abrogate selection processes. No variants formed in identical
      ethylbenzene-exposed controls. The results suggest that benzyl alcohol mediates
      irreversible defects in both a plasmid-associated meta pathway and an alternate
      chromosomal pathway.

PMID- 7642500
TI  - The Bacillus subtilis dacB gene, encoding penicillin-binding protein 5*, is part
      of a three-gene operon required for proper spore cortex synthesis and spore core
      dehydration.
AB  - Studies of gene expression using fusions to lacZ demonstrated that the Bacillus
      subtilis dacB gene, encoding penicillin-binding protein 5*, is in an operon with
      two downstream genes, spmA and spmB. Mutations affecting any one of these three
      genes resulted in the production of spores with reduced heat resistance. The
      cortex peptidoglycan in dacB mutant spores had more peptide side chains, a higher
      degree of peptide cross-linking, and possibly less muramic acid lactam than that
      of wild-type spores. These cortex structure parameters were normal in spmA and
      spmB mutant spores, but these spores did not attain normal spore core
      dehydration. This defect in spore core dehydration was exaggerated by the
      additional loss of dacB expression. However, loss of dacB alone did not alter the
      spore core water content. Spores produced by spmA and spmB mutants germinated
      faster than did those of the wild type. Spores produced by dacB mutants
      germinated normally but were delayed in spore outgrowth. Electron microscopy
      revealed a drastically altered appearance of the cortex in dacB mutants and a
      minor alteration in an spmA mutant. Measurements of electron micrographs indicate
      that the ratio of the spore protoplast volume to the sporoplast (protoplast-plus
      cortex) volume was increased in dacB and spmA mutants. These results are
      consistent with spore core water content being the major determinant of spore
      heat resistance. The idea that loosely cross-linked, flexible cortex
      peptidoglycan has a mechanical activity involved in achieving spore core
      dehydration is not consistent with normal core dehydration in spores lacking only
      dacB.

PMID- 7642501
TI  - Characterization of the exbBD operon of Escherichia coli and the role of ExbB and
      ExbD in TonB function and stability.
AB  - TonB protein appears to couple the electrochemical potential of the cytoplasmic
      membrane to active transport across the essentially unenergized outer membrane of
      gram-negative bacteria. ExbB protein has been identified as an auxiliary protein
      in this process. In this paper we show that ExbD protein, encoded by an adjacent
      gene in the exb cluster at 65', was also required for TonB-dependent energy
      transduction and, like ExbB, was required for the stability of TonB. The
      phenotypes of exbB exbD+ strains were essentially indistinguishable from the
      phenotypes of exbB+ exbD strains. Mutations in either gene resulted in the
      degradation of TonB protein and in decreased, but not entirely absent,
      sensitivities to colicins B and Ia and to bacteriophage phi 80. Evidence that the
      absence of ExbB or ExbD differentially affected the half-lives of newly
      synthesized and steady-state TonB was obtained. In the absence of ExbB or ExbD,
      newly synthesized TonB was degraded with a half-life of 5 to 10 min, while the
      half-life of TonB under steady-state conditions was significantly longer,
      approximately 30 min. These results were consistent with the idea that ExbB and
      ExbD play roles in the assembly of TonB into an energy-transducing complex. While
      interaction between TonB and ExbD was suggested by the effect of ExbD on TonB
      stability, interaction of ExbD with TonB was detected by neither in vivo cross
      linking assays nor genetic tests for competition. Assays of a chromosomally
      encoded exbD::phoA fusion showed that exbB and exbD were transcribed as an
      operon, such that ExbD-PhoA levels in an exbB::Tn10 strain were reduced to 4% of
      the levels observed in an exbB+ strain under iron-limiting conditions. Residual
      ExbD-PhoA expression in an exbB::Tn10 strain was not iron regulated and may have
      originated from within the Tn10 element in exbB.

PMID- 7642502
TI  - Effects of elemental sulfur on the metabolism of the deep-sea hyperthermophilic
      archaeon Thermococcus strain ES-1: characterization of a sulfur-regulated, non
      heme iron alcohol dehydrogenase.
AB  - The strictly anaerobic archaeon Thermococcus strain ES-1 was recently isolated
      from near a deep-sea hydrothermal vent. It grows at temperatures up to 91 degrees
      C by the fermentation of peptides and reduces elemental sulfur (S(o)) to H2S. It
      is shown here that the growth rates and cell yields of strain ES-1 are dependent
      upon the concentration of S(o) in the medium, and no growth was observed in the
      absence of S(o). The activities of various catabolic enzymes in cells grown under
      conditions of sufficient and limiting S(o) concentrations were investigated.
      These enzymes included alcohol dehydrogenase (ADH); formate benzyl viologen
      oxidoreductase; hydrogenase; glutamate dehydrogenase; alanine dehydrogenase;
      aldehyde ferredoxin (Fd) oxidoreductase; formaldehyde Fd oxidoreductase; and
      coenzyme A-dependent, Fd-linked oxidoreductases specific for pyruvate,
      indolepyruvate, 2-ketoglutarate, and 2-ketoisovalerate. Of these, changes were
      observed only with ADH, formate benzyl viologen oxidoreductase, and hydrogenase,
      the specific activities of which all dramatically increased in cells grown under
      S(o) limitation. This was accompanied by increased amounts of H2 and alcohol
      (ethanol and butanol) from cultures grown with limiting S(o). Such cells were
      used to purify ADH to electrophoretic homogeneity. ADH is a homotetramer with a
      subunit M(r) of 46,000 and contains 1 g-atom of Fe per subunit, which, as
      determined by electron paramagnetic resonance analyses, is present as a mixture
      of ferrous and ferric forms. No other metals or acid-labile sulfide was detected
      by colorimetric and elemental analyses. ADH utilized NADP(H) as a cofactor and
      preferentially catalyzed aldehyde reduction. It is proposed that, under So
      limitation, ADH reduces to alcohols the aldehydes that are generated by
      fermentation, thereby serving to dispose of excess reductant.

PMID- 7642503
TI  - Purification, characterization, and metabolic function of tungsten-containing
      aldehyde ferredoxin oxidoreductase from the hyperthermophilic and proteolytic
      archaeon Thermococcus strain ES-1.
AB  - Thermococcus strain ES-1 is a strictly anaerobic, hyperthermophilic archaeon that
      grows at temperatures up to 91 degrees C by the fermentation of peptides. It is
      obligately dependent upon elemental sulfur (S(o)) for growth, which it reduces to
      H2S. Cell extracts contain high aldehyde oxidation activity with viologen dyes as
      electron acceptors. The enzyme responsible, which we term aldehyde ferredoxin
      oxidoreductase (AOR), has been purified to electrophoretic homogeneity. AOR is a
      homodimeric protein with a subunit M(r) of approximately 67,000. It contains
      molybdopterin and one W, four to five Fe, one Mg, and two P atoms per subunit.
      Electron paramagnetic resonance analyses of the reduced enzyme indicated the
      presence of a single [4Fe-4S]+ cluster with an S = 3/2 ground state. While AOR
      oxidized a wide range of aliphatic and aromatic aldehydes, those with the highest
      apparent kcat/Km values (> 10 microM-1S-1) were acetaldehyde, isovalerylaldehyde,
      and phenylacetaldehyde (Km values of < 100 microM). The apparent Km value for
      Thermococcus strain ES-1 ferredoxin was 10 microM (with crotonaldehyde as the
      substrate). Thermococcus strain ES-1 AOR also catalyzed the reduction of acetate
      (apparent Km of 1.8 mM) below pH 6.0 (with reduced methyl viologen as the
      electron donor) but at much less than 1% of the rate of the oxidative reaction
      (with benzyl viologen as the electron acceptor at pH 6.0 to 10.0). The properties
      of Thermococcus strain ES-1 AOR are very similar to those of AOR previously
      purified from the saccharolytic hyperthermophile Pyrococcus furiosus, in which
      AOR was proposed to oxidize glyceraldehyde as part of a novel glycolytic pathway
      (S. Mukund and M. W. W. Adams, J. Biol. Chem. 266:14208-14216, 1991). However,
      Thermococcus strain ES-1 is not known to metabolize carbohydrates, and
      glyceraldehyde was a very poor substrate (kcat/Km of < 0.2 microM-1S-1) for its
      AOR. The most efficient substrates for Thermococcus strain ES-1 AOR were the
      aldehyde derivatives of transaminated amino acids. This suggests that the enzyme
      functions to oxidize aldehydes generated during amino acid catabolism, although
      the possibility that AOR generates aldehydes from organic acids produced by
      fermentation cannot be ruled out.

PMID- 7642504
TI  - Minimal requirements of the Streptomyces lividans 66 oriC region and its
      transcriptional and translational activities.
AB  - Deletion analysis of a previously constructed minichromosome revealed that a
      stretch of DNA which is longer than 623 bp but shorter than 837 bp is required
      for autonomous replication of the Streptomyces lividans chromosome. Each of the
      dnaA and dnaN genes flanking the oriC region is individually transcribed from two
      promoters. Within the intergenic, nontranslatable region between the dnaA and
      dnaN genes, five main transcripts and several less abundant transcripts of
      various lengths as well as one of the promoters were identified. The introduction
      of additional DnaA boxes in S. lividans led to a significant increase in dnaA
      gene transcripts and to an enhanced level of the DnaA (73-kDa) protein. In
      summary, the data suggest that dnaA gene transcription is autoregulated and that
      initiation of the S. lividans chromosome is tightly controlled.

PMID- 7642505
TI  - Integration of heterologous DNA into the genome of Paracoccus denitrificans is
      mediated by a family of IS1248-related elements and a second type of integrative
      recombination event.
AB  - All members of the IS1248 family residing in the genome of Paracoccus
      denitrificans have been isolated by using a set of insertion sequence entrapment
      vectors. The family consists of five closely related members that integrate the
      entrapment vectors at distinct sites. One of these, IS1248b, was sequenced and,
      except for a single base change, shown to be identical to the previously isolated
      IS1248a. Southern analysis of genomic DNA with labeled IS1248 revealed different
      hybridization patterns for different isolates of P. denitrificans and Thiosphaera
      pantotropha. No hybridization was observed with DNA from Thiobacillus versutus
      and more distantly related species. From a comparison of the fingerprints it was
      shown that one of the members of the IS1248 family found in P. denitrificans
      DSM413 is absent in strain NCIB8944, although they are catalogued in
      international strain catalogues as identical strains. Furthermore, strains Pd1222
      and Pd1235, both derivatives of P. denitrificans DSM413, were shown to have
      different patterns of IS1248 hybridizing restriction fragments. In 14 of 18
      strains, the entrapment vectors used in this study were incorporated into the
      genome via IS1248-mediated cointegrate formation. In the other four strains, the
      entrapment vectors were shown to be integrated through a different mechanism not
      involving IS1248.

PMID- 7642506
TI  - Bacterial conjugation mediated by plasmid RP4: RSF1010 mobilization, donor
      specific phage propagation, and pilus production require the same Tra2 core
      components of a proposed DNA transport complex.
AB  - DNA transfer by bacterial conjugation requires a mating pair formation (Mpf)
      system that specifies functions for establishing the physical contact between the
      donor and the recipient cell and for DNA transport across membranes. Plasmid RP4
      (IncP alpha) contains two transfer regions designated Tra1 and Tra2, both of
      which contribute to Mpf. Twelve components are essential for Mpf, TraF of Tra1
      and 11 Tra2 proteins, TrbB, -C, -D, -E, -F, -G, -H, -I, -J, -K, and -L. The
      phenotype of defined mutants in each of the Tra2 genes was determined. Each of
      the genes, except trbK, was found to be essential for RP4-specific plasmid
      transfer and for mobilization of the IncQ plasmid RSF1010. The latter process did
      not absolutely require trbF, but a severe reduction of the mobilization frequency
      occurred in its absence. Transfer proficiency of the mutants was restored by
      complementation with defined Tra2 segments containing single trb genes. Donor
      specific phage propagation showed that traF and each of the genes encoded by Tra2
      are involved. Phage PRD1, however, still adsorbed to the trbK mutant strain but
      not to any of the other mutant strains, suggesting the existence of a plasmid
      encoded receptor complex. Strains containing the Tra2 plasmid in concert with
      traF were found to overexpress trb products as well as extracellular filaments
      visualized by electron microscopy. Each trb gene and traF are needed for the
      formation of the pilus-like structures. The trbK gene, which is required for PRD1
      propagation and for pilus production but not for DNA transfer on solid media,
      encodes the RP4 entry-exclusion function. The components of the RP4 Mpf system
      are discussed in the context of related macromolecule export systems.

PMID- 7642508
TI  - Identification of Pseudomonas aeruginosa glpM, whose gene product is required for
      efficient alginate biosynthesis from various carbon sources.
AB  - In a mucB (algN) genetic background, insertion of an omega element approximately
      200 bp downstream of glpD, encoding sn-glycerol-3-phosphate dehydrogenase from
      Pseudomonas aeruginosa, had an adverse effect on alginate biosynthesis from
      various carbon sources. The insertion inactivated glpM, a gene encoding a 12,040
      M(r) hydrophobic protein containing 109 amino acids. This protein, which was
      expressed in a T7 RNA polymerase expression system, appears to be a cytoplasmic
      membrane protein.

PMID- 7642507
TI  - Sterigmatocystin biosynthesis in Aspergillus nidulans requires a novel type I
      polyketide synthase.
AB  - A filamentous fungus, Aspergillus nidulans, produces the carcinogenic mycotoxin
      sterigmatocystin (ST), which is a polyketide-derived secondary metabolite. A gene
      (pksST) encoding the ST polyketide synthase (PKSst) in A. nidulans was cloned,
      sequenced, and characterized. Large induced deletion mutants, which did not make
      ST or any ST intermediates, were used to identify genes associated with ST
      biosynthesis. Among the transcripts detected within the deletion region, which
      showed developmental expression with ST production, was a 7.2-kb transcript.
      Functional inactivation of the gene encoding the 7.2-kb transcript blocked
      production of ST and all ST intermediate substrates but did not affect
      transcription of the pathway genes, indicating that this gene was involved in a
      very early step of ST biosynthesis. These results also indicate that PKSst was
      not associated with activation of other ST genes. Sequencing of the region
      spanning this gene revealed that it encoded a polypeptide with a deduced length
      of 2,181 amino acids that had high levels of similarity to many of the known
      polyketide synthases and FASs. This gene, pksST, encodes a multifunctional novel
      type I polyketide synthase which has as active sites a beta-ketoacyl acyl carrier
      protein synthase, an acyltransferase, duplicated acyl carrier proteins, and a
      thioesterase, all of these catalytic sites may be multiply used. In addition, a
      1.9-kb transcript, which also showed developmental expression, was mapped
      adjacent to pksST, and the sequence of this gene revealed that it encoded a
      cytochrome P-450 monooxygenase-like peptide.

PMID- 7642509
TI  - Transcriptional induction and expression of the endoglucanase celA gene from a
      ruminal Clostridium sp. ("C. longisporum").
AB  - Northern (RNA) blot analysis of RNA from Clostridium sp. revealed induction of
      transcription of the celA gene when barley beta-glucan was used as carbon source,
      while no celA mRNA was detected after growth on cellobiose. Western blots
      (immunoblots), prepared by using a rabbit antiserum raised against CelA protein
      purified from Escherichia coli, revealed the extracellular location of CelA in
      Clostridium sp. Despite the absence of detectable celA mRNA, significant
      quantities of CelA were detected in the culture supernatant during growth on
      cellobiose. This finding indicated a low constitutive expression of celA. A 6.7
      fold increase in the total beta-glucanase specific activity in the extracellular
      fraction was observed during growth on beta-glucan. The transcriptional start
      site of celA was mapped by extension and was found to be the same in Clostridium
      sp. and in E. coli expressing the cloned celA gene. A consensus E. coli -10
      promoter region (AATAAT), but not a -35 promoter region, could be identified. Two
      direct repeats (TATTGAATTTAT) separated by 15 nucleotides flank the region where
      the consensus -35 promoter regions would have been. The size of the celA mRNA
      transcript corresponded with the size of the open reading frame. A potential stem
      loop structure was found 18 nucleotides downstream of the 3' stop codon, which
      could be responsible for termination of transcription.

PMID- 7642510
TI  - Identification of a methyl-specific restriction system mediated by a conjugative
      element from Streptomyces bambergiensis.
AB  - pBL2 was identified genetically but not physically in Streptomyces lividans after
      its mating with S. bambergiensis. During conjugation, pBL2 was transferred at
      high frequency to S. lividans and S. coelicolor. pBL2.1 DNA isolated from S.
      coelicolor exconjugants as a circular plasmid was shown to derive from the genome
      of S. bambergiensis. S. lividans carrying pBL2 or pBL2.1 acquired a methyl
      specific restriction (MsrA+) phenotype. The corresponding enzyme was partially
      purified and shown to resemble a class II endonuclease which cleaves Dam
      methylated DNA preferentially.

PMID- 7642511
TI  - Bacillus subtilis gnt repressor mutants that diminish gluconate-binding ability.
AB  - The Bacillus subtilis gnt operon is negatively regulated by GntR, which is
      antagonized by gluconate. Three GntR mutants with diminished gluconate-binding
      ability were obtained. Two were missense mutants (Met-209 to Ile and Ser-230 to
      Leu), whereas the third had a deletion of the C-terminal 23 amino acids. The
      mutant GntR proteins were unable to become properly detached from the gnt
      operator even in the presence of gluconate.

PMID- 7642512
TI  - Molecular characterization of the genes encoding the tungsten-containing aldehyde
      ferredoxin oxidoreductase from Pyrococcus furiosus and formaldehyde ferredoxin
      oxidoreductase from Thermococcus litoralis.
AB  - The hyperthermophilic archaea Pyrococcus furiosus and Thermococcus litoralis
      contain the tungstoenzymes aldehyde ferredoxin oxidoreductase, a homodimer, and
      formaldehyde ferredoxin oxidoreductase, a homotetramer. herein we report the
      cloning and sequencing of the P. furiosus gene aor (605 residues; M(r), 66,630)
      and the T. litoralis gene for (621 residues; M(r), 68,941).

PMID- 7642513
TI  - Activation of the Escherichia coli lacZ promoter by the Klebsiella aerogenes
      nitrogen assimilation control protein (NAC), a LysR family transcription factor.
AB  - A chimeric promoter with the nitrogen assimilation control protein binding site
      from hutUp of Klebsiella aerogenes fused to the lacZ core promoter from
      Escherichia coli was built and cloned in a lacZ reporter plasmid. This construct
      showed a 14-fold increase of beta-galactosidase activity upon nitrogen
      limitation. Primer extension experiments showed that the nitrogen assimilation
      control protein activates lacZp1 in a position-dependent manner.

PMID- 7642514
TI  - Transcription of spoIVB is the only role of sigma G that is essential for pro
      sigma K processing during spore formation in Bacillus subtilis.
AB  - Activation of pro-sigma K processing in the mother cell at late stages of
      sporulation in Bacillus subtilis requires the presence of active sigma G in the
      forespore. Placing the spoIVB gene under the control of sigma F, the early
      forespore transcription factor, allows sigma K to become active in the absence of
      sigma G. Therefore, transcription of spoIVB is the only role of sigma G that is
      essential for the signaling pathway between sigma G and sigma K.

PMID- 7642515
TI  - Lipid signaling enzymes and surface dilution kinetics.

PMID- 7642516
TI  - Cleavage of poly(ADP-ribose) polymerase by interleukin-1 beta converting enzyme
      and its homologs TX and Nedd-2.
AB  - The proteolytic cleavage of poly(ADP-ribose) polymerase (PARP) is an early
      biochemical event, which occurs during apoptosis. A recent study suggested that
      PARP cleavage can be mediated by a novel cytosolic protease (prICE) that
      resembles interleukin-1 beta converting enzyme (ICE), but cannot be mediated by
      ICE itself (Lazebnik, Y.A., Kaufmann, S.H., Desnoyers, S., Poirier, G.G., and
      Earnshaw, W.C. (1994) Nature 371, 346-347). We have used a COS cell co
      transfection assay to investigate if ICE or any known ICE-like protease is active
      in PARP cleavage within the cell. Here we report that co-expression of human PARP
      with human ICE, or the ICE homologs TX and Nedd-2, resulted in a cleavage of PARP
      identical to that observed in apoptotic cells. Experiments with purified
      recombinant human ICE indicated that PARP polypeptide can be specifically cleaved
      in vitro by ICE in a time- and enzyme concentration-dependent manner. PARP
      cleavage, however, requires a 50-100-fold higher ICE concentration than does
      processing of the interleukin-1 beta precursor at an equivalent substrate
      concentration. The abilities of ICE, TX, and Nedd-2, when expressed at high
      intracellular concentrations, to cleave PARP are consistent with their induction
      of apoptosis in transfected cells.

PMID- 7642517
TI  - Angiotensin II type 1a receptor-deficient mice with hypotension and
      hyperreninemia.
AB  - Angiotensin (AT) II, the bioactive octapeptide in the renin-angiotensin system
      that plays a key role in cardiovascular homeostasis, exerts its multiple effects
      through the different types of AT receptors, AT1a, AT1b, and AT2. Previously, we
      showed chronic hypotension in angiotensinogen (the precursor of AT)-deficient
      mice and a dramatic increase in renin mRNA levels in its kidney, but it remains
      unclear which types of AT receptors regulate the blood pressure and renin gene
      expression. In order to elucidate the physiological roles of AT1a receptor, we
      generated mutant mice with a targeted replacement of the AT1a receptor loci by
      the lacZ gene. In the heterozygous mutant mice, the strong lacZ staining was
      found in the glomerulus and juxtaglomerular apparatus of the renal cortex, which
      coincided with that of the signals detected by in situ hybridization. Chronic
      hypotension was observed in the heterozygous and homozygous mutant mice, with 10
      and 22 mm Hg lower systolic blood pressure, respectively, than that of wild-type
      littermates. Both levels of renin mRNA in the kidney and plasma renin activity
      were markedly increased only in the homozygous mutant mice. These results
      demonstrated that an AT1a-mediated signal transduction pathway is, at least in
      part, involved in the regulation of blood pressure and renin gene expression.

PMID- 7642518
TI  - Sterol carrier protein-2 is involved in cholesterol transfer from the endoplasmic
      reticulum to the plasma membrane in human fibroblasts.
AB  - The cellular mechanism of cholesterol transport from the endoplasmic reticulum to
      the plasma membrane is currently unknown. To assess the possibility that sterol
      carrier protein-2 (SCP-2) is involved in this transport, we studied the time
      course of newly synthesized cholesterol incorporation in the plasma membrane of
      normal and SCP-2-deficient (Zellweger syndrome) human fibroblasts. Cholesterol
      transfer was rapid, cytoskeleton-independent, and Golgi-independent in normal
      cells, but it was slower, cytoskeleton-dependent, and Golgi-dependent in SCP-2
      deficient cells. After SCP-2 antisense oligonucleotides treatment of normal
      fibroblasts, the rapid transport was reduced by 81% with a simultaneous increase
      of the slower one. These results suggest that in normal fibroblasts the major
      fraction of newly synthesized cholesterol is transported to the plasma membrane
      by a SCP-2-dependent mechanism. In contrast, in SCP-2-deficient cells, newly
      synthesized cholesterol leaves the endoplasmic reticulum by a cytoskeleton/Golgi
      dependent mechanism.

PMID- 7642519
TI  - Chromosomal location and structural organization of the human deoxycytidylate
      deaminase gene.
AB  - Deoxycytidylate deaminase is an allosteric enzyme whose impairment can lead to
      deoxynucleotide imbalances that affect the fidelity of DNA synthesis. A DNA
      fragment encompassing the gene for deoxycytidylate deaminase has been isolated
      from a human lung fibroblast genomic library and sequenced in both directions
      through 26,764 base pairs. The previously isolated cDNA, which was used to
      establish the amino acid sequence for this enzyme (Weiner, K.X.B., Weiner, R.S.,
      Maley, F., and Maley, G.F. (1993) J. Biol. Chem. 268, 12983-12989) was
      instrumental in isolating this gene. The gene consists of five exons of about 100
      base pairs each, separated by four introns. The most striking feature of the
      genomic structure is that the second and third exons are separated by an intron
      of about 20 kilobases. The chromosomal location of the deaminase gene was
      determined by fluorescence in situ hybridization as 4q35, which is the extreme
      end of this chromosome. The position of this gene on chromosome 4, in addition to
      the role of its product in limiting potentially detrimental mutations, suggests
      that the normal operation of both the gene and its product is important to the
      well being of the organism.

PMID- 7642520
TI  - Activating and inhibitory mutations in adjacent tyrosines in the kinase domain of
      ZAP-70.
AB  - ZAP-70 is an 70-kDa protein tyrosine kinase, expressed exclusively in T cells and
      NK cells, and plays a critical role in mediating T cell activation in response to
      T cell receptor engagement. The strong correlation between tyrosine
      phosphorylation of ZAP-70 and its acquisition of increased kinase activity
      suggests that is is positively regulated by tyrosine phosphorylation. Previously,
      we identified tyrosines 492 and 493 of ZAP-70 as being sites of in vivo
      phosphorylation in response to T cell receptor engagement. To determine the role
      of phosphorylation in regulating ZAP-70 activity, we mutated each of these
      tyrosines individually to phenylalanine. When expressed in COS cells, Y493F
      mutated ZAP-70 demonstrated normal basal kinase activity, but, unlike wild type
      ZAP-70, could not be activated by tyrosine phosphorylation induced by incubation
      with pervanadate or by co-expression of constitutively activated Lck. This
      suggests that Tyr-493 phosphorylation is required for the tyrosine
      phosphorylation-induced activation of ZAP-70. The Y492F mutation resulted in 4
      fold higher basal kinase activity, which could be stimulated further by tyrosine
      phosphorylation. These results reveal that critical tyrosine residues in the
      kinase domain of ZAP-70 are important in regulation of its catalytic activity.

PMID- 7642521
TI  - Fibroblast contractility without an increase in basal myosin light chain
      phosphorylation in wild type cells and cells expressing the catalytic domain of
      myosin light chain kinase.
AB  - We investigated the role of myosin light chain (MLC20) phosphorylation (MLC-P) in
      non-muscle contractility by comparing MLC-P and the contractile properties of
      wild type 3T3 fibroblasts and 3T3 fibroblasts expressing the catalytic domain of
      myosin light chain kinase (tMK). MLC-P is 0.96 MOL of PO4/mol of MOL20 in cell
      expressing tMK compared to 0.20 mol of PO4/mol of MLC20 in control cells.
      Expressing tMK also results in a 2-fold increase in cortical stiffness compared
      to control cells. Contractile properties were quantified by growing wild type and
      transfected fibroblasts in collagen and attaching the ensuing fibers to an
      apparatus for performing mechanical measurements. Serum stimulation resulted in a
      dose-dependent increase in force with maximal force generated in the presence of
      30% (v/v) serum. Surprisingly, MLC-P did not increase in wild type cells
      following stimulation with 30% serum, and tMK expression did not affect the
      contractile properties of fibers made from these cells. Moreover, the dose
      responses to serum, maximal force, force-velocity relationships, and dynamic
      stiffness were similar in the wild type cells and fibroblasts expressing tMK.
      These data demonstrate that non-muscle cells can generate force without an
      increase in MLC-P, and that an increase in MLC-P does not affect the contractile
      properties of fibroblast fibers.

PMID- 7642522
TI  - Distinct roles for N-ethylmaleimide-sensitive fusion protein (NSF) suggested by
      the identification of a second Drosophila NSF homolog.
AB  - The N-ethylmaleimide-sensitive fusion protein (NSF) is a cytoplasmic protein
      implicated in the fusion of intracellular transport vesicles with their target
      membranes. NSF is thought to function in the fusion of essentially all types of
      vesicles, including endoplasmic reticulum, Golgi, and endocytic vesicles, as well
      as secretory vesicles undergoing regulated fusion (for review see Rothman, J.E.
      (1994) Nature 372, 55-63). However, little experimental evidence exists to
      address the possibility that organisms might have multiple NSF proteins serving
      distinct functions in the same or different cells. We previously cloned a
      neurally expressed Drosophila homolog, dNSF-1 (Ordway, R.W., Pallanck, L., and
      Ganetzky, B. (1994) Proc. Natl. Acad. Sci. U.S.A. 91, 5715-5719), and have
      subsequently identified mutations in this gene that confer an apparent failure of
      synaptic transmission at elevated temperature (Pallanck, L., Ordway, R.W., and
      Ganetzky, B. (1995) Nature, 376, 25; Siddiqi, O., and Benzer, S. (1976) Proc.
      Natl. Acad. Sci. U.S.A. 73, 3253-3257). Here we report that 1) Drosophila
      contains a second NSF homolog, termed dNSF-2, that exhibits 84% amino acid
      identity to dNSF-1, 2) dNSF-1 and dNSF-2 display overlapping but different
      temporal expression, and 3) multiple transcripts are derived from the dNSF-2
      gene. These findings raise the possibility that different NSF gene products serve
      distinct or overlapping functions with the organism.

PMID- 7642523
TI  - Male germ cell-specific alteration in temperature set point of the cellular
      stress response.
AB  - Heat shock factor (HSF), a transcriptional regulator with heat-activatable DNA
      binding ability, mediates the stress-induced expression of eukaryotic heat shock
      protein genes. Previous results from this laboratory demonstrated that a
      preparation of mixed male germ cell types from mouse testis exhibited a lower
      temperature threshold for activation of HSF1 DNA binding relative to other mouse
      cell types (Sarge, K.D., Bray, A.E., and Goodson, M.L. (1995) Nature 374, 126).
      The purpose of the present study was to determine whether the phenomenon of
      reduced HSF1 activation temperature is common to all testis cell types, both
      somatic and germ cell types, or whether it is a special property of male germ
      cells. The results show that a purified population of pachytene spermatocytes,
      one of the male germ cell types, exhibits a profile of reduced HSF1 activation
      temperature identical to that observed for the mixed germ cell preparation, with
      a threshold HSF1 activation temperature of 35 degrees C. Activation of HSF1 DNA
      binding in male germ cells by incubation at 38 degrees C is accompanied by the
      classic cellular stress response parameters of heat-induced HSF1 phosphorylation
      and increased expression of the hsp72 stress protein. In contrast, a preparation
      of somatic testis cell types exhibits HSF1 activation only at temperatures of 42
      degrees C and above, a profile identical to that observed for mouse liver cells
      and mammalian cell lines. These results demonstrate that the phenomenon of
      reduced HSF1 activation temperature is a unique property of male germ cell types
      within the mammalian testis and demonstrate that HSF1 activated at this lower
      temperature threshold is fully capable of mediating a productive cellular stress
      response in these cell types.

PMID- 7642524
TI  - Differential roles of de novo sphingolipid biosynthesis and turnover in the
      "burst" of free sphingosine and sphinganine, and their 1-phosphates and N-acyl
      derivatives, that occurs upon changing the medium of cells in culture.
AB  - Long-chain (sphingoid) bases are highly bioactive intermediates for sphingolipid
      metabolism, yet relatively little is known about how the amounts of these
      compounds are regulated. This study used J774A.1 cells to characterize the
      "burst" of sphinganine and sphingosine, or the transient increase of up to 10
      fold in long-chain base mass, that occurs when cells in culture are changed to
      fresh medium. The increase in sphinganine was attributable to de novo
      sphingolipid biosynthesis because: 1) there is increased incorporation of
      [3H]serine and [3H]palmitate into sphinganine; 2) the incorporation of [3H]serine
      was equivalent to the increase in sphinganine mass; 3) beta-F-alanine, an
      inhibitor of serine palmitoyltransferase, blocked the sphinganine burst; 4) the
      magnitude of the burst depended on the concentration of serine in the medium,
      which is known to affect long-chain base biosynthesis; and 5) the appearance of
      sphinganine was relatively unaffected by lyso-osmotrophic agents (NH4Cl and
      chloroquine) that blocked sphingolipid hydrolysis in these cells. In contrast,
      the sphingosine burst arose mainly from turnover of complex sphingolipids because
      no incorporation of [3H]serine or [3H]palmitate into sphingosine was detected;
      sphingosine mass was not affected by beta-F-alanine or the serine concentration;
      and, the burst could be followed by the release of sphingosine and ceramide from
      complex sphingolipids (especially sphingomyelin) in a process that was inhibited
      by NH4Cl and chloroquine. Additionally, the fate of these long-chain bases
      differed: sphinganine was mostly (80-85%) acylated and incorporated into
      dihydroceramide and complex sphingolipids, whereas most of the sphingosine (70%)
      was phosphorylated and degraded, with incorporation of the resulting ethanolamine
      phosphate into phosphatidylethanolamine. Sphinganine, however, could be diverted
      toward degradation by adding an inhibitor of N-acylation (fumonisin B1). In
      accounting for the elevation in sphingosine and sphinganine after cells are
      changed to new medium, these studies have provided fundamental information about
      long-chain base metabolism. The existence of differential changes in sphinganine
      and sphingosine, as well as their 1-phosphates and N-acyl-derivatives, should be
      considered when evaluating the roles of sphingolipid metabolites in cell
      regulation.

PMID- 7642525
TI  - Regulation of the mouse histone H2A.X gene promoter by the transcription factor
      E2F and CCAAT binding protein.
AB  - We have molecularly cloned the genomic gene encoding the mouse histone variant
      H2A.X and characterized the promoter. The promoter region of the H2A.X gene was
      characterized by chloramphenicol acetyltransferase analysis using Balb/c 3T3
      cells. Maximal promoter activity was found in the construct containing up to -282
      base pairs H2A.X upstream region. Within this region, we found two sequences
      regulating the promoter activation; one was an E2F site and another was a CCAAT
      box. These sequences were also required for the DNA/protein binding activities.
      Thus, these activities corresponded to the promoter activities, implying that the
      promoter activity H2A.X gene was controlled by both the transcription factor E2F
      and H1TF2 through the E2F and CCAAT element. The CCAAT box binding activity was
      constitutive when cell cycle was progressed by release from G1 arrest, but
      transiently transfected chloramphenicol acetyltransferase activity slightly
      increased when cells entered S phase. Similarly, the level of the smallest form
      of E2F (free E2F) became higher when cells reentered the cell cycle, indicating
      that the free E2F was one capable of inducing the promoter activation. Thus, the
      free E2F and CCAAT DNA binding activity correlated with regulation of the
      promoter activity.

PMID- 7642526
TI  - Multiple ubiquitin C-terminal hydrolases from chick skeletal muscle.
AB  - A new method for assaying ubiquitin C-terminal hydrolases was developed using a
      125I-labeled ubiquitin-alpha NH-MHISPPEPESEEEEEHYC was substrate. Since the
      peptide portion was almost exclusively radiolabeled, the enzymes could be assayed
      directly by simple measurement of the radioactivity released into acid-soluble
      products. Using this assay protocol, we identified at least 10 ubiquitin C
      terminal hydrolase activities from the extract of chick skeletal muscle, which
      were tentatively named UCHs 1 through 10. Of these, UCH-6 was purified to
      apparent homogeneity. Purified UCH-6 behaved as a dimer of 27-kDa subunits. The
      apparent molecular masses of the other partially purified UCHs ranged from 35 to
      810 kDa as determined under a non-denaturing condition. Muscle UCHs, except UCH
      1, were activated dramatically by poly-L-Lys but with an unknown mechanism. All
      of the UCHs were sensitive to inhibition by sulfhydryl-blocking agents such as
      iodoacetamide. In addition, all of the UCHs were capable of releasing free
      ubiquitin from a ubiquitin-alpha NH-carboxyl extension protein of 80 amino acids
      and from ubiquitin-alpha NH-dihydrofolate reductase. Five of the enzymes, UCHs 1
      through 5, were also capable of generating free ubiquitin from poly-His-tagged
      diubiquitin. In addition, UCH-1 and UCH-7 could remove ubiquitin that had been
      ligated covalently by an isopeptide linkage to a ubiquitin (RGA)-alpha NH
      peptide, the peptide portion of which consists of the 20 amino acids of the
      calmodulin binding domain of myosin light chain kinase. These results suggest
      that the 10 UCH activities isolated from chick skeletal muscle appear to be
      distinct from each other at least in their chromatographic behavior, size, and
      substrate specificity.

PMID- 7642528
TI  - A gastric housekeeping Cl- channel activated via prostaglandin EP3 receptor
      mediated Ca2+/nitric oxide/cGMP pathway.
AB  - Prostaglandin E2 (PGE2) has a cytoprotective role in the gastric parietal cell.
      PGE2 opened a housekeeping basolateral Cl- channel of rabbit gastric parietal
      cells, the single channel conductance of which was about 0.3 picosiemens. In the
      present patch-clamp and Fura 2 fluorescence studies, we found that PGE2 increased
      the intracellular free Ca2+ concentration ([Ca2+]i) and that PGE2-induced opening
      of the Cl- channel depended on the increase of [Ca2+]i. A novel bifunctional
      prostaglandin EP3 agonist/EP1 antagonist, 5(Z)-7-[1S, 2S, 3S, 5R)-3-(trans-beta
      styren) sulfonamido-6,6-dimethylbicyclo- (3.1.1)hept-2-yl]-5-heptenoic acid, also
      increased both [Ca2+]i and channel opening. The PGE2-induced effect was mediated
      via production of nitric oxide (NO); that is, NG-monomethyl-L-arginine, an
      inhibitor of NO production, markedly inhibited the PGE2-induced channel opening,
      and nitroprusside, a NO donor, induced the channel opening in the absence of
      PGE2. Both PGE2 and A23187, Ca2+ ionophore, elevated the cGMP content of isolated
      parietal cells. The A23187-induced channel opening was abolished by methylene
      blue, a guanylate cyclase inhibitor. In conclusion, we found that the PGE2
      induced opening of the housekeeping Cl- channel in the parietal cell involves the
      EP3 receptor-mediated increase in [Ca2+]i via a pertussis toxin-sensitive GTP
      binding protein, resulting in successive production of NO and cGMP.

PMID- 7642527
TI  - Regulation of phospholipid biosynthesis in Saccharomyces cerevisiae by CTP.
AB  - In the yeast Saccharomyces cerevisiae, the major membrane phospholipid
      phosphatidylcholine is synthesized by the CDP-diacylglycerol and CDP-choline
      pathways. We examined the regulation of phosphatidylcholine synthesis by CTP. The
      cellular concentration of CTP was elevated (2.4-fold) by overexpressing CTP
      synthetase, the enzyme responsible for the synthesis of CTP. The overexpression
      of CTP synthetase resulted in a 2-fold increase in the utilization of the CDP
      choline pathway for phosphatidylcholine synthesis. The increase in CDP-choline
      pathway usage was not due to an increase in the expression of any of the enzymes
      in this pathway. CDP-choline, the product of the phosphocholine
      cytidylyltransferase reaction, was the limiting intermediate in the CDP-choline
      pathway. The apparent Km of CTP (1.4 mM) for phosphocholine cytidylyltransferase
      was 2-fold higher than the cellular concentration of CTP (0.7 mM) in control
      cells. This provided an explanation of why the overexpression of CTP synthetase
      caused an increase in the cellular concentration of CDP-choline.
      Phosphatidylserine synthase activity was reduced in cells overexpressing CTP
      synthetase. This was not due to a transcriptional repression mechanism. Instead,
      the decrease in phosphatidylserine synthase activity was due, at least in part,
      to a direct inhibition of activity by CTP. These results show that CTP plays a
      role in the regulation of the pathways by which phosphatidylcholine is
      synthesized. This regulation includes the supple of CTP for the phosphocholine
      cytidylyltransferase reaction in the CDP-choline pathway and the inhibition of
      the phosphatidylserine synthase reaction in the CDP-diacylglycerol pathway.

PMID- 7642529
TI  - Tissue-specific enhancer-promoter interactions regulate high level constitutive
      expression of matrix metalloproteinase 2 by glomerular mesangial cells.
AB  - The 72-kDa gelatinase A (MMP-2) is a central mediator of the response of the
      intrinsic glomerular mesangial cell to inflammatory stimuli and is regulated in a
      unique, cell-specific manner. We isolated a 6-kilobase pair genomic fragment of
      the rat MMP-2 gene and sequenced and characterized 1686-base pair of the 5'
      flanking region. Using a series of 5' deletion constructs of the proximal 5'
      flanking region, a strong MMP-2 enhancer element was identified. Gel shift and
      mutational analyses suggest tha the enhancer region represents the binding site
      for complex transcription factor demonstrating separable DNA-binding and
      transcriptional activating domains. The presence and activity of the enhancer
      element was evaluated in several cell types with varying capabilities to
      synthesize MMP-2 including mesangial cells, glomerular epithelial cells, and the
      monocytic U937 cell. Although binding activity was present in all cell types
      studied, enhancer activity was demonstrated only in mesangial and glomerular
      epithelial cells. Additional transcriptional control resided in a tissue-specific
      promoter, which supported transcription only in mesangial cells. These results
      indicate that the final control of mesangial cell-specific synthesis of MMP-2
      derives from an interaction between the strong enhancer element and the tissue
      specific MMP-2 promoter.

PMID- 7642530
TI  - Substrate control of free radical generation from xanthine oxidase in the
      postischemic heart.
AB  - While the free radical-generating enzyme xanthine oxidase is a central mechanism
      of injury in postischemic tissues, questions remain regarding how xanthine
      oxidase-mediated radical generation is triggered during ischemia and reperfusion.
      There is controversy regarding whether radical generation is caused by enzyme
      formation of that of its substrates xanthine and hypoxanthine. Therefore, studies
      were performed in isolated rat hearts correlating the magnitude and time course
      of radical generation with alteration in xanthine oxidase and its substrates.
      Radical generation was measured by electron paramagnetic resonance spectroscopy
      and correlated with spectrophotometric assays of tissue xanthine oxidase activity
      and chromatographic measurements of tissue and effluent concentrations of
      xanthine oxidase substrates and products. Xanthine oxidase was present in
      preischemic hearts and slightly increased during 30-min global ischemia.
      Hypoxanthine and xanthine were not present prior to ischemia but accumulated
      greatly during ischemia due to ATP degradation. These substrate concentrations
      rapidly declined over the first 5 min of reperfusion matching the observed time
      course of radical generation, whereas xanthine oxidase activity was largely
      unchanged. Both substrates were also observed in the coronary effluent during the
      first 5 min of reflow along with the product uric acid. Thus, the burst of
      xanthine oxidase-mediated free radical generation upon reperfusion is triggered
      and its time course controlled by a large increase in substrate formation that
      occurs secondary to the degradation of ATP during ischemia.

PMID- 7642531
TI  - A novel G protein alpha subunit containing atypical guanine nucleotide-binding
      domains is differentially expressed in a molluscan nervous system.
AB  - We described the characterization of a novel G protein alpha subunit, G alpha a.
      cDNA encoding this subunit was cloned from the central nervous system of the
      mollusc Lymnaea stagnalis. The deduced protein contains all characteristic
      guanine nucleotide-binding domains of G alpha subunits but shares only a limited
      degree of overall sequence identity with known subtypes (approximately 30%).
      Moreover, two of the nucleotide-binding domains exhibit salient deviations from
      corresponding sequences in other G protein alpha subunits. The A domain,
      determining kinetic features of the GTPase cycle, contains a markedly unique
      amino acid sequence (ILIIGGPGAGK). In addition, the C domain is also clearly
      distinct (DVAGQRSL). The presence of a leucine in this motif, instead of glutamic
      acid, has important implications for hypotheses concerning the GTPase mechanism.
      In contrast to other G alpha subtypes, G alpha a has no appropriate N-terminal
      residues that could be acylated. It does contain the strictly conserved arginine
      residue that serves as a cholera toxin substrate in G alpha s and G alpha t but
      lacks a site for ADP-ribosylation by pertussis toxin. In situ hybridization
      experiments indicate that G alpha a-encoding mRNA is expressed in a limited
      subpopulation of neurons within the Lymnaea brain. These data suggest that G
      alpha a defines a separate class of G proteins with cell type-specific functions.

PMID- 7642532
TI  - The cytoplasmic domain of the Drosophila cell adhesion molecule neuroglian is not
      essential for its homophilic adhesive properties in S2 cells.
AB  - Drosophila neuroglian is a transmembrane glycoprotein that has strong structural
      and sequence homology to the vertebrate L1 gene family of cell adhesion molecules
      (Bieber, A.J., Snow, P.M., Hortsch, M., Patel, N.H., Jacobs, J.R., Traquina,
      Z.R., Schilling, J., and Goodman, C.S. (1989) Cell 59, 447-460. Two different
      neuroglian protein forms that are generated by a differential splicing process
      are expressed in a tissue-specific fashion by embryonic and larval cells
      (Hortsch, M., Bieber, A.J., Patel, N.H., and Goodman, C.S. (1990) Neuron 4, 697
      709). The two neuroglial polypeptides differ only in their cytoplasmic domains.
      Both of these neuroglian species, when transfected into the expressed in
      Drosophila S2 cells, induce the calcium-independent, homophilic aggregation of
      transformed cells. A third artificial neuroglian protein form was constructed by
      substituting the neuroglian transmembrane segment and cytoplasmic domains with
      the glycosyl phosphatidylinositol attachment signal of the Drosophila fasciclin I
      protein. This cDNA construct generates a glycosyl phosphatidylinositol-anchored
      form of neuroglian, which retains the ability to induce homophilic cell
      aggregation when expressed in S2 cells, and was able to interact with both of the
      two naturally occurring neuroglian polypeptides. These results demonstrate that
      neuroglian mediates a calcium-independent, homophilic cell adhesion activity and
      that neither cytoplasmic neuroglian domains nor a direct interaction with
      cytoskeletal elements is essential for this property.

PMID- 7642533
TI  - Identification of two new genes in the Pseudomonas aeruginosa amidase operon,
      encoding an ATPase (AmiB) and a putative integral membrane protein (AmiS).
AB  - The nucleotide sequence of the amidase operon of Pseudomonas aeruginosa has been
      completed and two new genes identified amiB and amiS. The complete gene order for
      the operon is thus amiEBCRS. The amiB gene encodes a 42-kDa protein containing an
      ATP binding motif that shares extensive homology with the Clp family of proteins
      and also to an open reading frame adjacent to the amidase gene from Rhodococcus
      erythropolis. Deletion of the amiB gene has no apparent effect on inducible
      amidase expression and it is thus unlikely to encode a regulatory protein. A
      maltose-binding protein-AmiB fusion has been purified and shown to have an
      intrinsic ATPase activity (Km = 174 +/- 15 mM; Vmax = 2.4 +/- 0.1 mM/min/mg),
      which is effectively inhibited by ammonium vanadate and ADP. The amiS gene
      encodes an 18-kDa protein with a high content of hydrophobic residues. Hydropathy
      analysis suggests the presence of six transmembrane helices in this protein. The
      AmiS sequences is homologous to an open reading frame identified adjacent to the
      amidase gene from Mycobacterium smegmatis and to the ureI gene from the urease
      operon of Helicobacter pylori. AmiS and its homologs appear to be a novel family
      of integral membrane proteins. Together AmiB and AmiS resemble two components of
      an ABC transporter system.

PMID- 7642534
TI  - Blue light-induced reactivity of retinal age pigment. In vitro generation of
      oxygen-reactive species.
AB  - Exposure of the eye to intense light, particularly blue light, can cause
      irreversible, oxygen-dependent damage to the retina. However, no key chromophores
      that trigger such photooxidative processes have been identified yet. We have
      found that illumination of human retinal pigment epithelium (RPE) cells with
      light induces significant uptake of oxygen that is both wavelength- and age
      dependent. Analysis of photoreactivity of RPE cells and their age pigment
      lipofuscin indicates that the observed photoreactivity in RPE cells is primarily
      due to the presence of lipofuscin, which, under aerobic conditions, generates
      several oxygen-reactive species including singlet oxygen, superoxide anion, and
      hydrogen peroxide. We have also found that lipofuscin-photosensitized aerobic
      reactions lead to enhanced lipid peroxidation as measured by accumulation of
      lipid hydroperoxides and malondialdehyde in illuminated pigment granules.
      Hydrogen peroxide is only a minor product of aerobic photoexcitation of
      lipofuscin. We postulate that lipofuscin is a potential photosensitizer that may
      increase the risk of retinal photodamage and contribute to the development of age
      related maculopathy.

PMID- 7642535
TI  - Decrease in cell viability due to the accumulation of spermidine in spermidine
      acetyltransferase-deficient mutant of Escherichia coli.
AB  - Physiological functions of spermidine acetyltransferase in Escherichia coli have
      been studied using the spermidine acetyltransferase (speG) gene-deficient mutant
      CAG2242 and the cloned speG gene. The growth of E. coli CAG2242 in the defined M9
      medium was normal in the presence and absence of 0.5mM spermidine. However, cell
      viability of E. coli CAG2242 at 48 h after the onset of growth decreased greatly
      by the addition of 0.5 mM spermidine. The amount of spermidine accumulated in the
      cells was approximately 3-fold that in the cells grown in the absence of
      spermidine. Transformation of the cloned speG gene to E. coli CAG2242 recovered
      the cell viability. Decreased in cell viability of E. coli CAG2242 was observed
      even when 0.5mM spermidine was added at 24 h after the onset of growth. The
      results indicate that accumulated spermidine functions at the late stationary
      phase of growth. The accumulation of spermidine caused a decrease in protein
      synthesis but not in DNA and RNA synthesis at 28 h after the onset of growth. The
      synthesis of several kinds of proteins was particularly inhibited. They included
      ribosome modulation factor and OmpC protein. Since the ribosome modulation factor
      is essential for cell viability at the stationary phase of growth (Yamagishi, M.,
      Matsushima, H., Wada, A., Sakagami, M., Fujita, N., and Ishihama, A. (1993) EMBO
      J. 12, 625-630), the decrease in the protein was thought to be one of the reasons
      for the decrease in cell viability. The decrease in the ribosome modulation
      factor mainly occurred at the translational level.

PMID- 7642536
TI  - Cytokine induction of nuclear factor kappa B in cycling and growth-arrested
      cells. Evidence for cell cycle-independent activation.
AB  - Nuclear factor kappa B (NF-kappa B) is a pleiotropic transcription factor which
      regulates the expression of a large number of cellular and viral genes. Induction
      of NF-kappa B has been shown previously to occur during cell cycle transition
      from G0 to G1, but the relationship of cytokine induction of this transcription
      factor to cell cycling has not been directly addressed. Here we examine the
      inductions of NF-kappa B in serum-deprived and cycling cells in response to tumor
      necrosis factor-alpha (TNF-alpha). In 3T3 fibroblasts deprived of serum, and in
      the temperature-sensitive G2 phase mutant carcinoma line FT210, we find that NF
      kappa B DNA binding activity is rapidly induced upon addition of TNF-alpha. In
      addition, NF-kappa B induction in cycling cells occurs without a significant
      change in cell cycle distribution. These data reveal that NF-kappa B is rapidly
      induced by TNF-alpha in both proliferating and arrested cells and suggest that
      distinct activation pathways can lead to cell cycle-dependent or -independent
      induction of NF-kappa B.

PMID- 7642537
TI  - The 23-kDa acidic protein in reticulocyte lysate is the weakly bound component of
      the hsp foldosome that is required for assembly of the glucocorticoid receptor
      into a functional heterocomplex with hsp90.
AB  - The heat shock proteins hsp90 and hsp70 have been immunopurified from rabbit
      reticulocyte lysate in a multiprotein complex that acts as a self-sufficient
      protein folding machine. This immunopurified "foldosome" directs the assembly of
      the glucocorticoid receptor-hsp90 complex and refolds the receptor to the steroid
      binding state (Hutchison, K.A., Dittmar, K.D., and Pratt, W.B. (1994) J. Biol.
      Chem. 269, 27894-27899). Extensive washing of the immunoadsorbed foldosome
      eliminates a weakly bound component required for receptor heterocomplex assembly
      and folding. This protein factor is contained in a Centricon C-100 filtrate of
      lysate which reconstitutes the receptor activating activity of the washed
      foldosome. This hsp90-associated protein folding system is present in both animal
      and plant cells, and the Centricon C-100 fraction of rabbit reticulocyte lysate
      potentiates receptor folding directed by wheat germ lysate. We have used this
      ability to stimulate wheat germ lysate-directing folding of the glucocorticoid
      receptor as a rapid assay for the factor. We demonstrate that the activity
      segregates with the 23-kDa acidic protein component of the hsp90 foldosome when
      rabbit reticulocyte lysate is fractionated by ammonium sulfate precipitation and
      ion exchange chromatography. Immunoadsorption of the Centricon C-100 filtrate
      with a monoclonal antibody against p23 eliminates its ability to stimulate the
      wheat germ heterocomplex assembly/receptor folding system, and the activity is
      replaced by purified, bacterially expressed p23. Immunodepletion of p23 also
      eliminates the ability of the Centricon C-100 filtrate to reconstitute receptor
      activating activity of the washed foldosome and addition of purified, bacterially
      expressed p23 restores its activity, confirming that p23 is the weakly bound
      component of the foldosome complex required for refolding of the receptor to the
      steroid binding conformation.

PMID- 7642538
TI  - Divergent functional roles for p90rsk kinase domains.
AB  - A unique and highly conserved structural feature of approximately 90-kDa
      ribosomal S6 kinase (p90rsk or RSK) is the presence of two non-identical kinase
      domains. To explore the mechanism of RSK activation, a cloned human RSK cDNA
      (RSK3) was used to generate and characterize several site-directed RSK mutants;
      K91A (N-Lys, NH2-terminal ATP-binding mutant), K444A (C-Lys, COOH-terminal ATP
      binding mutant), N/C-Lys (double ATP-binding mutant) T570A (C-Thr, mutant of the
      putative MAPK phosphorylation site in subdomain VIII of the C-domain), S218A (N
      Ser, mutant of the corresponding NH2-terminal residue). Epitope-tagged RSKs were
      expressed in transfected COS cells followed by immunoprecipitation with or
      without prior in vivo epidermal growth factor stimulation. Kinase activity (S6
      peptide) of N/C-Lys and N-Lys was ablated (and partially impaired with N-Ser). In
      contrast, both C-Lys and C-Thr retained high levels of kinase activity and were
      capable of responding to stimulation. C-Lys also retained partial kinase activity
      toward other substrates (c-Fos, S40 ribosomes, protein phosphatase 1 G-subunit,
      histones, and Leu-Arg-Arg-Ala-Ser-Leu-Gly (Kemptide)) whereas N-Lys did not. The
      isolated NH2-and COOH-terminal domains were also expressed; the C-domain was
      inactive, whereas the N-domain retained partial activity. Relative to wild-type,
      both N-Lys and C-Lys (as well as N-Ser and C-Thr) underwent partial in vitro
      autophosphorylation that was further stimulated by EGF protein tyrosine
      phosphatase. We conclude that 1) the NH2-terminal RSK kinase domain mediates
      substrate phosphorylation; 2) both domains contribute to autophosphorylation; 3)
      the putative MAPK phosphorylation site is not required for growth factor
      stimulated autophosphorylation or kinase activation.

PMID- 7642539
TI  - A locus of the gonadotropin-releasing hormone receptor that differentiates
      agonist and antagonist binding sites.
AB  - The decapeptide gonadotropin-releasing hormone controls reproductive function via
      interaction with a heptahelical G protein-coupled receptor. Because of molecular
      model of the receptor predicts that Lys121 in the third transmembrane helix
      contributes to the binding pocket, the function of this side chain was studied by
      site-directed mutagenesis. Substitution of Arg at this position preserved high
      affinity agonist binding, whereas Gln at this position reduced binding below the
      limits of detection. Leu and Asp at this locus abolished both binding and
      detectable signal transduction. The EC50 of concentration-response curves for
      coupling to phosphatidyl inositol hydrolysis obtained with the Gln121 receptor
      was more than 3 orders of magnitude higher than that obtained for the wild-type
      receptor. In order to determine whether the increased EC50 obtained with this
      mutant reflects an altered receptor affinity, the effect of decreases in wild
      type receptor density on concentration-response curves was determined by
      irreversible antagonism. Progressively decreasing the concentration of the wild
      type receptor increased the EC50 values obtained to a maximal level of 2.4 +/-
      0.2 nM. Comparison of this value with the EC50 of 282 +/- 52 nM observed with the
      Gln121 receptor mutant indicates that the agonist affinity for this mutant is
      reduced more than 100-fold. In contrast, antagonist had comparable high
      affinities for the wild-type, Arg121, and Gln121 mutants. The results indicate
      that a charge-strengthened hydrogen bond donor is required at this locus for high
      affinity agonist binding but not for high affinity antagonist binding.

PMID- 7642540
TI  - Carboxyl-terminal domains determine internalization and recycling characteristics
      of bombesin receptor chimeras.
AB  - To investigate the role of the carboxy terminus in the regulation of the bombesin
      (BN) receptor, we constructed two chimeric receptors with carboxyl termini
      transferred from either m3 muscarinic cholinergic (m3 ACh) (BMC) or
      cholecystokinin A (CCKA) (BCC) receptors and expressed them in Chinese hamster
      ovary cells. Previous studies showed that agonist treatment caused rapid
      internalization of CCKA but not m3 ACh receptors in these cells. In the current
      study we conducted separate analyses of ligand and receptor internalization and
      analyzed receptor recycling. Ligand internalization was assessed using acid
      washing. BN and CCKA receptors internalized ligand with 80 +/- 3 and 85 +/- 7% in
      an acid-resistant compartment at equilibrium. Ligand internalization of chimeric
      receptors generally assumed the properties of the donor receptors. Thus, BCC
      receptors internalized ligand to a similar extent as wild-type CCKA receptors (75
      +/- 3%), whereas, BMC receptors showed reduced ligand internalization (38 +/-
      1%). Receptor internalization was more directly assessed by determining agonist
      induced loss of surface binding. BN and CCKA receptors were largely internalized
      (56 +/- 8 and 50 +/- 7%, respectively). BCC receptors were also extensively
      internalized (82 +/- 3%). In contrast, BMC receptors were minimally internalized
      (22 +/- 8%). Receptor recycling was assessed as recovery from agonist induced
      loss of binding. BN, CCKA, and BMC receptors showed rapid recycling. In contrast,
      BCC receptors did not recycle. These data indicate that carboxyl-terminal
      structures determine both internalization of ligand-receptor complexes and
      subsequent receptor recycling.

PMID- 7642541
TI  - Structural analysis of cross-linking domains in cartilage type XI collagen.
      Insights on polymeric assembly.
AB  - The collagen framework of hyaline cartilage is based on copolymers of types II,
      IX, and XI collagens. Previous studies have established specific covalent
      interactions between types II and IX collagens. The present study examined cross
      linking sites in type XI collagen to define better the full heteropolymeric
      assembly. Pepsinsolubilized type XI collagen was purified from fetal bovine
      cartilage. The cross-linking amino acids in the preparation were primarily
      divalent, borohydride-reducible structures; pyridinoline residues were
      essentially absent. Individual alpha 1(XI), alpha 2(XI), and alpha 3(XI) chains
      were resolved by high performance liquid chromatography. Telopeptides still
      attached by cross-links to helical sites were released by periodate oxidation and
      identified by microsequencing. Analysis of cross-linked peptides isolated from
      trypsin digest of each alpha-chain identified the attachment helical sites for
      the telopeptides. A high degree of interchain specificity was evident in the
      cross-linking between N-telopeptides and the COOH terminus of the triple-helix,
      consistent with a head-to-tail interaction of molecules staggered by 4D (D = 67
      nm) periods. In addition, alpha 1(II) C-telopeptide was linked to the amino
      terminal site of the alpha 1(XI) triple helix. In summary, the results show that
      type XI collagen molecules are primarily cross-linked to each other in cartilage,
      implying that a homopolymer is initially formed. Links to type II collagen are
      also indicated, consistent with an eventual cofibrillar assembly. Analysis of
      cartilage extracts showed that all three chains, alpha 1(XI), alpha 2(XI), and
      alpha 3(XI), had at least in part retained their N-propeptides in cartilage
      matrix and that the alpha 3 (XI) chain was the IIB splicing variant product of
      the COL2A1 gene. Of particular note was the finding that the N-telopeptide cross
      linking site in both alpha 1(XI) and alpha 2(XI) is located amino-terminal to the
      putative N-propeptidase cleavage site. This structural feature provides a
      potential mechanism for the proteolytic depolymerization of type XI collagen by
      proteases that can cleave between the cross-link and the triple helix (e.g.
      stromelysin).

PMID- 7642543
TI  - 13,14-Dihydroxy-retinol, a new bioactive retinol metabolite.
AB  - Deprivation of vitamin A (retinol) leads to reduced potential of B cell
      proliferation and nearly complete block of T cell activation in vitro. Retinol,
      which is thought to function as a pro-hormone, is enzymatically converted into
      intracellular messenger molecules. Thus, 14-hydroxy-retro-retinol (14-HRR) is an
      intracellular messenger molecule linked to activation and growth regulation of
      lymphocytes; whereas, anhydroretinol, another natural retro-retinoid, is an
      antagonist of 14-HRR effects. In this article, we describe the isolation,
      structure determination, synthesis, and biological properties of a new
      intracellular retinol derivative, 13,14-dihydroxy-retinol (DHR), which also
      supports the viability of retinol-deprived lymphocytes. DHR is found in numerous
      cell lines representing a large cross-section of tissues and animals from insects
      to mammals. In T lymphocytes the production of DHR and 14-HRR is up-regulated by
      phorbol ester. DHR is converted to 14-HRR by mild acid treatment, but not by
      cells; therefore DHR is not a biosynthetic intermediate in the conversion of
      retinol to 14-HRR. DHR is a distinct end point of retinol metabolism. Although it
      is linked to cell proliferation, its biological role remains to be determined.

PMID- 7642542
TI  - Ionizing radiation stimulates a Grb2-mediated association of the stress-activated
      protein kinase with phosphatidylinositol 3-kinase.
AB  - The stress-activated protein (SAP) kinases are induced by tumor necrosis factor,
      oncoproteins, and UV light. The present studies demonstrate that ionizing
      radiation (IR) activates p54 SAP kinase. IR-induced activation of SAP kinase is
      associated with binding to the SH2/SH3-containing adaptor protein Grb2. This
      interaction is mediated by the SH3 domains of Grb2 and the proline-rich sequence
      PPPKIP in the carboxy-terminal region of SAP kinase. We also demonstrated that
      SAP kinase and the p85 alpha-subunit of phosphatidylinositol (PI) 3-kinase form a
      complex in irradiated cells. The results indicate that this complex involves
      binding of the p85 alpha subunit of PI 3-kinase to the SH2 domain of Grb2. The
      functional role of linking SAP kinase to PI 3-kinase is further supported by the
      finding that wortmannin, an inhibitor of PI 3-kinase, stimulates SAP kinase
      activity. These results suggest that the cellular response to IR may include
      regulation of SAP kinase by a PI 3-kinase-dependent signaling pathway.

PMID- 7642544
TI  - Involvement of a putative protein-tyrosine phosphatase and I kappa B-alpha serine
      phosphorylation in nuclear factor kappa B activation by tumor necrosis factor.
AB  - Inhibitors of phosphotyrosyl protein phosphatases, pervanadate and phenylarsine
      oxide, abrogate tumor necrosis factor (TNF)-induced nuclear factor kappa B (NF
      kappa B) nuclear translocation in transformed cell lines (U-937 and Jurkat) and
      primary fibroblasts (MRC-5 and REF). The inhibitors also abrogate NF-kappa B
      activation by the phosphoseryl/threonyl protein phosphatase inhibitor okadaic
      acid in U-937 cells. Inhibition of NF-kappa B activation is not due to a general
      inhibitory effect since neither pervanadate nor phenylarsine oxide treatment
      affected the constitutive DNA-binding activity of the transcription factors
      octamer-1 and cAMP response element-binding protein in U-937 cells, nor did these
      compounds inhibit the TNF-induced phosphorylation of proteins, viz. hsp-27,
      eukaryotic initiation factor 4e, and pp19, in MRC-5 fibroblasts. Overexpression
      of the protein-tyrosine phosphatase HPTP alpha resulted in a constitutive nuclear
      NF-kappa B-like DNA-binding activity in REF cells. Conversely, treatment of human
      protein-tyrosine phosphatase alpha-overexpressing cells with phenylarsine oxide
      led to a loss of the constitutive NF-kappa B activity. The presence of a tyrosine
      phosphorylation site on the inhibitor of NF-kappa B (I kappa B-alpha) suggested
      that it could be a target for TNF/okadaic acid-induced tyrosine
      dephosphorylation. However, no tyrosine phosphorylation was detected on I kappa B
      alpha fron unstimulated cells, while TNF/okadaic acid-treated cells showed
      increased phosphorylation of I kappa B-alpha exclusively at serine residue(s).
      Treatment of cells with pervanadate inhibited TNF-induced I kappa B-alpha
      phosphorylation and degradation, whereas the serine protease inhibitors
      tosylphenylalanyl chloromethyl ketone and N alpha-p-tosyl-L-lysine chloromethyl
      ketone prevented TNF-induced I kappa B-alpha degradation and NF-kappa B nuclear
      translocation, but not the TNF-induced phosphorylation of I kappa B-alpha. The
      data suggest that TNF and okadaic acid induce the activation of a putative
      protein-tyrosine phosphatase(s), leading to I kappa B-alpha serine
      phosphorylation and degradation and NF-kappa B nuclear translocation.

PMID- 7642545
TI  - A novel nonhepatic hydroxycholesterol 7 alpha-hydroxylase that is markedly
      stimulated by interleukin-1 beta. Characterization in the immature rat ovary.
AB  - During studies on the regulation of rat ovarian steroidogenic enzymes by
      interleukin-1 beta (IL-1 beta), we observed substantial metabolism of 25
      hydroxycholesterol to two unusual polar products. This unexpected effect was
      observed both in isolated granulosa cells and in whole ovarian dispersates and
      was also induced by tumor necrosis factor alpha, but not by insulin-like growth
      factor I or follicle-stimulating hormone. The effect was dependent on time and
      the dose of IL-1 beta and was blocked by and IL-1 receptor antagonist. The
      formation of the polar metabolites was inhibited by ketoconazole and trilostane,
      but not by aminoglutethimide. Subsequent purification of these novel metabolites
      and analysis by gas chromatography/ mass spectrometry, NMR, and high performance
      liquid chromatography revealed them to be related 7 alpha-hydroxylated
      hydroxycholesterols (cholest-4-ene-7 alpha,25-diol-3-one and cholest-5-ene-3
      beta,7 alpha,25-triol). IL-1 beta-stimulated ovarian 7 alpha-hydroxylase activity
      (3-10 pmol/min/mg of cellular protein) was nearly 4-fold that of control levels
      using 25-hydroxycholesterol as substrate. Activities at or below control levels
      were observed when IL-1 beta-treated cell sonicates were boiled or assayed in the
      presence of NADH (rather than NADPH), indicating that involvement of a
      nonenzymatic process was unlikely. IL-1 beta-stimulated 7 alpha-hydroxylase
      activity was inhibited to basal levels by a 10-fold excess of unlabeled 25- or 27
      hydroxycholesterol, but not by cholesterol, pregnenolone, progesterone,
      testosterone, or dehydroepiandrosterone, suggesting that ovarian 7 alpha
      hydroxylase is specific for hydroxycholesterols. Furthermore, when IL-1 beta
      treated ovarian cultures were incubated with radiolabeled cholesterol or
      testosterone, no 7 alpha-hydroxylated products were observed. We were also unable
      to detect any mRNA transcripts for liver cholesterol 7 alpha-hydroxylase in IL-1
      beta-stimulated ovarian cultures. This study describes an ovarian
      hydroxycholesterol 7 alpha-hydroxylase that differs from liver cholesterol 7
      alpha-hydroxylase and from other nonhepatic progestin/ androgen 7 alpha
      hydroxylases. The novel finding of the regulation of a 7 alpha-hydroxylase by IL
      1 beta (and tumor necrosis factor alpha) suggests a unique role for cytokines in
      the regulation of cholesterol metabolism in the ovary and possibly other tissues.

PMID- 7642546
TI  - The cathodic hemoglobin of Anguilla anguilla. Amino acid sequence and oxygen
      equilibria of a reverse Bohr effect hemoglobin with high oxygen affinity and high
      phosphate sensitivity.
AB  - As in other fish, the cathodic hemoglobin of the eel Anguilla anguilla is
      considered to play an important role in oxygen transport under hypoxic and
      acidotic conditions. In the absence of phosphates this hemoglobin shows a reverse
      Bohr effect and high oxygen affinity, which is strongly modulated over a side pH
      range by GTP (whose concentration in the red blood cells varies with ambient
      oxygen availability). GTP obliterates the reverse Bohr effects in the cathodic
      hemoglobin. The molecular basis for the reverse Bohr effect in fish hemoglobins
      has remained obscure due to the lack of structural data. We have determined the
      complete amino acid sequence of the alpha and beta chains of the cathodic
      hemoglobins of A. anguilla and relate it to the oxygen equilibrium
      characteristics. Several substitutions in crucial positions are observed compared
      with other hemoglobins, such as the replacement of the C-terminal His of the beta
      chain of Phe (that suppresses the alkaline Bohr effect) and of residues at the
      switch region between alpha and beta subunits (that may alter the allosteric
      equilibrium, thus causing the high intrinsic oxygen affinity and low
      cooperativity). The residues binding organic phosphate in the beta cleft of fish
      hemoglobins are conserved, which explains the strong effect of GTP on oxygen
      affinity and suggests that these residues contribute to the reverse Bohr effect
      in the absence of alkaline Bohr groups. Moreover, His beta 143 that is considered
      to be responsible for the reverse Bohr effect in human and tadpole Hbs is
      replaced by Lys.

PMID- 7642547
TI  - Sequence and structure requirements for Drosophila tRNA 5'- and 3'-end
      processing.
AB  - Eukaryotic tRNAs are processed at their 5'- and 3'- ends by endonucleases RNase P
      and 3'-tRNase, respectively. We have prepared substrates for both enzymes,
      separated the activities from a Drosophila extract, and designed variant tRNAs to
      assess the effects of sequence and structure on processing. Mutations affect
      these reactions in similar ways; thus, RNase P and 3'-tRNase probably require
      similar substrate structures to maintain the catalytic fit. RNase P is more
      sensitive to substrate substitutions than 3'-tRNase. In three of the four stems,
      one substitution prevents both processing reactions while the opposite one has
      less effect; anticodon stem substitutions hardly affect processing, and double
      substitution intended to restore base pairing also restore processing to the wild
      type rate. Structure probing suggests that tRNA misfolding sometimes coincides
      with reduced processing. In other cases, processing inhibition probably results
      from specific unfavorable stem appositions leading to local helix deformation. A
      single T loop substitution disrupts the tertiary D-T loop interaction and reduces
      processing. We have thus begun mapping tRNA processing determinants on the
      global, local, and tertiary structure levels.

PMID- 7642548
TI  - Molecular cloning and characterization of the human prostanoid DP receptor.
AB  - A cDNA encoding a functional human prostanoid DP (hDP) receptor has been
      constructed from a genomic clone and a fragment cloned by 3'-rapid amplification
      of cDNA ends-polymerase chain reaction. The hDP receptor consists of 359 amino
      acid residues with a predicted molecular mass of 40,276 and has the putative
      heptahelical transmembrane domains characteristics of G-protein-coupled
      receptors. The deduced amino acid sequence of the hDP receptor, when compared
      with all other members of the prostanoid receptor family, shows the highest
      degree of identity with the hIP and hEP2 receptors, followed by the hEP4
      receptor. Radioreceptor binding studies using membranes prepared from mammalian
      COS-M6 cells transiently transfected with an expression vector containing the DP
      receptor cDNA showed that the rank order of affinities for prostaglandins and
      prostaglandin analogs, in competition for [3H]prostaglandin D2 (PGD2) specific
      binding sites, was as predicted for the DP receptor, with PGD2 >> PGE2 > PGF2
      alpha = iloprost > U46619. The signal transduction pathway of the cloned hDP
      receptor was studied by transfecting the hDP expression vector in HEK 293(EBNA)
      cells. Activation of the hDP receptor with PGD2 resulted in an elevation of
      intracellular cAMP and in mobilization of Ca2+, but did not lead to generation of
      inositol 1,4,5-trisphosphate. Northern blot analysis of human tissue showed that
      the hDP receptor was a very discrete tissue distribution and was detectable only
      in retina and small intestine. In summary, we have cloned and expressed a
      functional cDNA for the hDP receptor.

PMID- 7642549
TI  - Detection of phosphorylated Ser262 in fetal tau, adult tau, and paired helical
      filament tau.
AB  - Paired helical filaments (PHFs) are the major structural elements of Alzheimer's
      disease neurofibrillary lesions, and these filaments are formed from
      hyperphosphorylated brain tau known as PHF-tau. Recent studies showed that many
      previously identified phosphorylated residues in PHF-tau also are phosphate
      acceptor sites in fetal and rapidly processed adult brain tau. However, Ser262
      has been suggested to be uniquely phosphorylated in PHF-tau and a key regulator
      of the binding of tau to microtubules. For these reasons, we generated a
      monoclonal antibody (12E8) specific for phosphorylated Ser262 and showed that
      12E8 binds to PHF-tau, rat and human fetal brain tau, as well as to rapidly
      processed adult rat and biopsy-derived human brain tau. Further, phosphorylation
      Ser262 was developmentally regulated, and endogenous brain phosphatases rapidly
      dephosphorylated Ser262 in biopsy-derived brain tau isolates. Finally, the
      phosphorylation of Ser262 did not eliminate the binding of tau to microtubules.
      Thus, we speculate that the binding of tau to microtubules is regulated by
      phosphorylation at multiple sites and that the generation of PHF-tau in
      Alzheimer's disease results from the reduced efficiency of phosphatases leading
      to the incremental accumulation of hyperphosphorylated tau.

PMID- 7642550
TI  - Efficient incorporation of anti-HIV deoxynucleotides by recombinant yeast
      mitochondrial DNA polymerase.
AB  - Saccharomyces cerevisiae mtDNA polymerase, isolated as a single 135-kDa
      recombinant polypeptide, showed high processivity and a capacity of use
      poly(dA).oligo(dT), poly(rA).oligo(dT), or primed bacteriophage M13 DNA as a
      template. In a primer extension assay, the enzyme exhibited an intrinsic 3'-5'
      exonuclease activity. By optimizing the polymerization reaction conditions,
      apparent Km and Vmax values could be determined for the incorporation of dTTP, 2'
      3'-dideoxy-TTP (ddTTP), 3'-azido-TTP (AZTTP), 3'-fluoro-TTP, dCTP, 2'-3'-dideoxy
      CTP, and didehydro(d4)CTP. The yeast mtDNA polymerase used ddTTP, 3'-fluoro-TTP,
      and ddCTP almost as efficiently as natural deoxynucleoside trisphosphates. Both
      3'AZTTP and d4CTP were each significantly less efficient as substrates. Overall,
      the kinetic data with mtDNA polymerase were very similar to those of the
      recombinant human immunodeficiency virus reverse transcriptase control.
      Terminally incorporated AZTTP or ddTTP was not removed by the 3'-5' exonuclease
      activity of mtDNA polymerase. This may explain the inhibition of mtDNA
      replication observed in anti-human immunodeficiency virus treatment with
      dideoxynucleoside analogs for their effects of mtDNA polymerase could be of value
      in future rational drug design.

PMID- 7642551
TI  - FK506 binding protein mutational analysis. Defining the surface residue
      contributions to stability of the calcineurin co-complex.
AB  - The 12- and 13-kDa FK506 binding proteins (FKBP12 and FKBP13) are cis-trans
      peptidyl-prolyl isomerases that bind the macrolides FK506 (Tacrolimus) and
      rapamycin (Sirolimus). The FKBP12.FK506 complex is immunosuppressive, acting as
      an inhibitor of the protein phosphatase calcineurin. We have examined the role of
      the key surface residues of FKBP12 and FKBP13 in calcineurin interactions by
      generating substitutions at these residues by site-directed mutagenesis. All
      mutants are active catalysts of the prolyl isomerase reaction, and bind FK506 or
      rapamycin with high affinity. Mutations at FKBP12 residues Asp-37, Arg-42, His
      87, and Ile-90 decrease calcineurin affinity of the mutant FKBP12.FK506 complex
      by as much as 2600-fold in the case of I90K. Replacement of three FKBP13 surface
      residues (Gln-50, Ala-95, and Lys-98) with the corresponding homologous FKBP12
      residues (Arg-42, His-87, and Ile-90) generates an FKBP13 variant that is
      equivalent to FKBP12 in its affinity for FK506, rapamycin, and calcineurin. These
      results confirm the role of two loop regions of FKBP12 (residues 40-44 and 84-91)
      as part of the effector face that interacts with calcineurin.

PMID- 7642552
TI  - Homodimeric and heterodimeric aryl sulfotransferases catalyze the sulfuric acid
      esterification of N-hydroxy-2-acetylaminofluorene.
AB  - Three aryl sulfotransferases (ASTs) isolated from rat liver catalyze the sulfuric
      acid esterification of the carcinogen N-hydroxy-2-acetylaminofluorene (N-OH
      2AAF). These three ASTs were separated by high resolution anion exchange
      chromatography and were designated Q1, Q2, and Q3. Q1 and Q2 had high N-OH-2AAF
      sulfonation activity, whereas Q3 showed low activity. Reversed phase high
      performance liquid chromatography/mass spectrometry analysis showed Q1-Q3 to be
      comprised of 33,945- and 35,675-Da protein subunits. Q1 contained only the 35,675
      Da protein subunit, Q2 contained equal quantities of 33,945- and 35,675-Da
      subunits, and Q3 contained only the 33,945-Da subunit. The subunit compositions
      of Q1-Q3 were confirmed by immunochemical analysis. Size exclusion high
      performance liquid chromatography confirmed that the active quaternary structure
      of the three isoenzymes was dimeric. Analysis of liver cytosols for the relative
      contributions of Q1-Q3 to total cytosolic N-OH-2AAF sulfotransferase activity
      indicated the Q1, Q2, and Q3 accounted for 44, 46, and 10% of the activity,
      respectively. These results demonstrate the existence of both homodimeric and
      heterodimeric aryl sulfotransferases and show that two ASTs, a homodimer of
      35,675-Da subunits and a heterodimer of a 33,945- and a 35,675-Da subunit, are
      primarily responsible for hepatic N-OH-2AAF sulfotransferase activity.

PMID- 7642553
TI  - Identification of an inhibitory domain of CTP:phosphocholine
      cytidylyltransferase.
AB  - The function of the putative amphipathic helices between residues 236 and 314 of
      CTP:phosphocholine cytidylyltransferase was examined by constructing two
      truncation mutants; CT314 was missing the entire phosphorylation segment, whereas
      CT236 was missing both the region with the putative amphipathic helices and the
      phosphorylation segment. Stable cells lines expressing these truncation mutants
      in Chinese hamster ovary 58 cells were isolated and characterized. CT314 was
      predominantly soluble in control cells but became membrane-associated in cells
      treated with oleate, which also causes translocation of wild-type
      cytidylyltransferase. CT236 was found to be soluble both in control cells and in
      cells treated to cause translocation. These results strongly suggest that the
      membrane-binding site is located within residues 237-314. When assayed for
      activity in vitro, the mutant forms were catalytically active in the presence of
      exogenous lipids. CT236, moreover, was as active in the absence of lipids as in
      their presence, whereas CT314 required lipids for activity. The rate of
      phosphatidylcholine synthesis in cells expressing CT236 was considerably higher
      than in wild-type cells, consistent with the enzyme being constitutively active
      in the cells. These results indicate that residues 237-314 constitute an
      inhibitory segment; when this segment is removed from the catalytic domain by
      truncation or by binding to membranes, an inhibitory constraint is removed and
      cytidylyltransferase is activated.

PMID- 7642554
TI  - Rapid and long-term effects on protein kinase C on receptor tyrosine kinase
      phosphorylation and degradation.
AB  - Rapid and long term effects of protein kinase C alpha activation on receptor
      tyrosine kinase signaling parameters were investigated in human 293 embryonic
      fibroblasts and mouse NIH 3T3 cells. Within minutes of phorbol 12-myristate 13
      acetate treatment, epidermal growth factor receptor and HER2 tyrosine
      phosphorylation was decreased, while platelet-derived growth factor receptor and
      insulin receptor autophosphorylation was upregulated. These effects are not
      mediated by protein kinase C-dependent receptor tyrosine kinase phosphorylation
      but apparently by activation or inactivation of receptor tyrosine kinase-specific
      phosphatases, as indicated by neutralization of these phenomena upon treatment of
      cells with sodium orthovanadate. In contrast to these short term effects,
      sustained activation of protein kinase C alpha by phorbol 12-myristate 13-acetate
      results in translocation of protein kinase C from the cytosol to the membrane
      fraction where it forms stable complexes with all receptor tyrosine kinases
      investigated. Ligand-induced receptor tyrosine kinase/protein kinase C
      association in NIH 3T3 fibroblasts is accompanied by a mobility shift of the
      receptor, indicating phosphorylation by activated protein kinase C. This
      phenomenon correlates with the disappearance of receptor tyrosine kinases from
      the cell surface, implying that this interaction plays a role in the process of
      receptor internalization and degradation. Interestingly, ligand-stimulated
      receptor down-regulation is also enhanced by overexpression of phospholipase C
      gamma, which strongly indicates a role for this common receptor tyrosine kinase
      substrate in negative regulation of growth factor signals.

PMID- 7642555
TI  - c-Myc is glycosylated at threonine 58, a known phosphorylation site and a
      mutational hot spot in lymphomas.
AB  - c-Myc is a helix-loop leucine zipper phosphoprotein that heterodimerizes with Max
      and regulates gene transcription in cell proliferation, cell differentiation, and
      programmed cell death. Previously, we demonstrated that c-Myc is modified by O
      linked N-acetylglucosamine (O-GlcNAc) within or nearby the N-terminal
      transcriptional activation domain (Chou, T.-Y., Dang, C.V., and Hart, G.W. (1995)
      Proc. Natl. Acad. Sci. U.S.A. 92, 4417-4421). In this paper, we identified the O
      GlcNAc attachment site(s) on c-Myc. c-Myc purified from sf9 insect cells was
      trypsinized, and its GlcNAc moieties were enzymically labeled with [3H]galactose.
      The [3H]galactose-labeled glycopeptides were isolated by reverse phase high
      performance liquid chromatography and then subjected to gas-phase sequencing,
      manual Edman degradation, and laser desorption/ionization mass spectrometry.
      These analyses show that threonine 58, an in vivo phosphorylation site in the
      transactivation domain, is the major O-GlcNAc glycosylation site of c-Myc.
      Mutation of threonine 58, frequently found in retroviral v-Myc proteins and in
      human Burkitt and AIDS-related lymphomas, is associated with enhanced
      transforming activity and tumorigenicity. The reciprocal glycosylation and
      phosphorylation at this biologically significant amino acid residue may play an
      important role in the regulation of the functions of c-Myc.

PMID- 7642556
TI  - H2O2 and tumor necrosis factor-alpha activate intercellular adhesion molecule 1
      (ICAM-1) gene transcription through distinct cis-regulatory elements within the
      ICAM-1 promoter.
AB  - We investigated the mechanisms by which H2O2 increases intercellular adhesion
      molecule 1 (ICAM-1; CD54) expression in endothelial cells. The H2O2-induced
      increase in ICAM-1 mRNA was inhibited by actinomycin D, by the antioxidant N
      acetylcysteine, and by 3-amino-benzamide (which blocks oxidant-induced AP-1
      activity), but not by pyrrolidine dithiocarbamate (which blocks oxidant-induced
      NF-kappa B activity). Nuclear run-on and transient transfections of ICAM-1
      promoter constructs indicated that H2O2 stimulated ICAM-1 gene transcription by
      activation of a distinct region of the ICAM-1 promoter. The H2O2-responsive
      element was localized to sequences between -981 and -769 (relative to start
      codon). Located within this region are two 16-base pair repeats, each containing
      binding sites for the transcription factors AP-1 and Ets. A similar composite AP
      1/Ets element isolated from the macrophage scavenger receptor gene conferred H2O2
      responsiveness to a minimal promoter. Mutation of the 16-base pair repeats within
      the ICAM-1 promoter prevented H2O2-induced DNA binding activity, and their
      deletion abrogated the H2O2-induced transcriptional activity. In contrast, TNF
      alpha induced ICAM-1 transcription via activation of promoter sequences between 
      393 and -176, a region with C/EBP and NF-kappa B binding sites. The results
      indicate that H2O2 activates ICAM-1 transcription through AP-1/Ets elements
      within the ICAM-1 promoter, which are distinct from NF-kappa B-mediated ICAM-1
      expression induced by TNF alpha.

PMID- 7642557
TI  - Identification of the magnesium-binding domain of the high-affinity ATP-binding
      site of the Bacillus subtilis and Escherichia coli SecA protein.
AB  - The homodimeric SecA protein is the peripheral subunit of the translocase, and
      couples the hydrolysis of ATP to the translocation of precursor proteins across
      the bacterial cytoplasmic membrane. The high affinity ATP binding activity of
      SecA resides in the amino-terminal domain of SecA. This domain contains a tandem
      repeat of the "so-called" Walker B-motif, hXhhD (Walker, J.E., Saraste, M.,
      Runswick, M.J., and Gay, N.J. (1982) EMBO J. 1, 945-951), that in combination
      with motif A is responsible for the Mg(2+)-phosphate protein interaction. Two
      aspartate residues at positions 207 and 215 of the Bacillus subtilis SecA, and
      Asp-217 in the Escherichia coli SecA, that could be Mg2+ ion ligands, were
      individually mutated to an asparagine. Mutant SecA proteins were unable to growth
      complement an E. coli secA amber mutant strain, and the E. coli SecA mutant
      interfered with the translocation of precursor proteins in vivo. B. subtilis
      mutant SecA proteins were expressed to a high level and purified to homogeneity.
      The high affinity ATP and Mg(2+)-ion binding activity was reduced in the Asp-207
      mutant, and completely lost in the Asp-215 mutant. Both SecA proteins were
      defective in lipid-stimulated ATPase activity. Proteolytic studies suggest that
      the two subunits of the mutated dimeric SecA proteins are present in different
      conformational states. These data suggest that Asp-207 and Asp-215 are involved
      in the binding of the Mg(2+)-ion when Mg(2+)-ATP is bound to SecA, while Asp-207
      fulfills an additional catalytic role, possibly in accepting a proton during
      catalysis.

PMID- 7642558
TI  - C-type natriuretic peptide increases bone resorption in 1,25-dihydroxyvitamin D3
      stimulated mouse bone marrow cultures.
AB  - Most agents that regulate osteoclast bone resorption exert their effects
      indirectly, through the osteoblast. Nitric oxide, which stimulates soluble
      guanylyl cyclase, has been reported to inhibit osteoclast bone resorption
      directly, by a cGMP-independent mechanism (1). In this report, we demonstrate
      that C-type natriuretic peptide (CNP), an activator of membrane-bound guanylyl
      cyclase, stimulates bone resorption by osteoclast-containing 1,25
      dihydroxyvitamin D3 (1,25-(OH)2D3)-stimulated mouse bone marrow cultures.
      Quantitative reverse transcription polymerase chain reaction assays and anti-CNP
      immunocytochemistry were used to demonstrate that CNP is expressed in mouse
      marrow cells cultured in the presence, but not the absence, of, 1,25-(OH)2D3.
      mRNA for guanylyl cyclase type B, the receptor for CNP, was expressed in cultures
      independent of 1,25-(OH)2D3. CNP (1 and 10 microM) elevated cGMP production in
      marrow cultures to 350 and 870%, respectively, of control values. 10 microM CNP
      increased osteoclast bone resorptive activity, measured by the resorption area on
      whale dentine wafers, or by the NH4Cl-inhibitable release of [3H]proline from
      radiolabeled bone chips, to 214 and 557% of control, respectively, without
      affecting osteoclast formation. Bone resorption by the marrow cultures was
      inhibited by 7F9.1, a monoclonal antibody raised against CNP, but not by control
      antibodies. These results indicate that CNP is a potent activator of osteoclast
      activity and may be a novel local regulator of bone remodeling.

PMID- 7642559
TI  - Adducin: a physical model with implications for function in assembly of spectrin
      actin complexes.
AB  - Adducin binds to spectrin-actin complexes, promotes association of spectrin with
      actin, and is subject to regulation by calmodulin as well as protein kinases A
      and C. Adducin is a heteromer comprised of homologous alpha and beta-subunits
      with an NH2-terminal protease-resistant head domain, connected by a neck region
      to a COOH-terminal hydrophilic, protease-sensitive region. This study provides
      evidence that adducin in solution is a mixture of heterodimers and tetramers. CD
      spectroscopy of COOH-terminal domains of alpha- and beta-adducin bacterial
      recombinants provides direct evidence for an unstructured random coil
      configuration. Cross-linking, proteolysis, and blot-binding experiments suggest a
      model for the adducin tetramer in which four head domains contact one another to
      form a globular core with extended interacting alpha- and beta-adducin tails. The
      site for binding to spectrin-actin complexes on adducin was identified as the
      COOH-terminal tail of both the alpha- and beta-adducin subunits. The capacity of
      native adducin to recruit spectrin to actin filaments is similar to that of
      adducin tail domains. Thus, adducin tail domains alone are sufficient to interact
      with F-actin and a single spectrin and to recruit additional spectrin molecules
      to the ternary complex.

PMID- 7642560
TI  - Cellular and molecular barriers to gene transfer by a cationic lipid.
AB  - Cationic lipids are widely used for gene transfer in vitro and show promise as a
      vector for in vivo gene therapy applications. However, there is limited
      understanding of the cellular and molecular mechanisms involved. We investigated
      the individual steps in cationic lipid-mediated gene transfer to cultured cell
      lines. We used DMRIE/DOPE (a 1:1 mixture of N-[1-(2,3-dimyristyloxy) propyl]-N,N
      dimethyl-N-(2-hydroxyethyl)ammonium bromide (DMRIE) and dioleoyl
      phosphatidylethanolamine (DOPE) as a model lipid because of its efficacy and
      because it is being used for clinical trials in humans. The data show that
      cationic lipid-mediated gene transfer is an inefficient process. Part of the
      inefficiency may result from the fact that the population of lipid-DNA complexes
      was very heterogeneous, even under conditions that have been optimized to produce
      the best transfection. Inefficiency was not due to inability of the complex to
      enter the cells because most cells took up the DNA. However, in contrast to
      previous speculation, the results indicate that endocytosis was the major
      mechanism of entry. After endocytosis, the lipid-DNA aggregated into large
      perinuclear complexes, which often showed a highly ordered tubular structure.
      Although much of the DNA remained aggregated in a vesicular compartment, there
      was at least a small amount of DNA in the cytoplasm of most cells. That
      observation plus results from direct injection of DNA and lipid-DNA into the
      nucleus and cytoplasm indicate that movement of DNA from the cytoplasm to the
      nucleus may be one of the most important limitations to successful gene transfer.
      Finally, before transcription can occur, the data show that lipid and DNA must
      dissociate. These results provide new insights into the physical limitations to
      cationic lipid-mediated gene transfer and suggest that attention to specific
      steps in the cellular process may further improve the efficiency of transfection
      and increase its use in a number of applications.

PMID- 7642561
TI  - A binding interface on the I domain of lymphocyte function-associated antigen-1
      (LFA-1) required for specific interaction with intercellular adhesion molecule 1
      (ICAM-1).
AB  - Previous studies have shown that lymphocyte function-associated antigen-1 (LFA-1)
      molecules containing the human alpha (CD11a) and human beta (CD18) subunits but
      not the murine alpha and human beta subunits can bind to human intercellular
      adhesion molecule 1 (ICAM-1). Using human/mouse LFA-1 alpha subunit chimeras, we
      mapped regions required for binding to ICAM-1 N-terminal to amino acid (aa)
      residue 350. Ligand binding sites were mapped in greater detail by scanning this
      region with murine sequences from 56 down to 17 aa in length and finally by
      introducing single or few murine aa residue replacements into the human sequence.
      Replacement of two non-contiguous regions of aa residues 119-153 and 218-248 in
      the me domain with the corresponding mouse sequences abolished most binding to
      human ICAM-1, without affecting alpha beta subunit association or expression on
      the surface of transfected COS cells. Specific residues within the I domain found
      to be important were Met-140, Glu-146, Thr-243, and Ser-245. Using the recently
      solved structure of the Mac-1 (CD11b) I domain as a model (Lee, J.-O., Rieu, P.,
      Arnaout, M.A., and Liddington, R. (1995) Cell 80, 631-638), these residues are
      shown to be located on the surface of the I domain surrounding the site to which
      Mg2+ is chelated, and fine a ligand binding interface. Mapping of the epitopes of
      a panel of mouse anti-human and rat anti-mouse monoclonal antibodies gave
      concordant results. Epitopes were mapped to two different regions in the N
      terminal domain, four regions within the I domain, and two regions between the I
      domain and the EF hand-like repeats. Monoclonal antibodies to epitopes within the
      mid- to C-terminal portion of the I domain and the N-terminal portion of the
      region between the I domain and the EF hand-like repeats gave good inhibition of
      LFA-1-dependent homotypic aggregation with cells that express either ICAM-1 or
      ICAM-3 as the major LFA-1 ligand.

PMID- 7642562
TI  - The essential yeast nucleoporin NUP159 is located on the cytoplasmic side of the
      nuclear pore complex and serves in karyopherin-mediated binding of transport
      substrate.
AB  - We have identified a new yeast nucleoporin of 159 kDa that we term NUP159.
      Immunofluorescence microscopy with a monospecific monoclonal antibody against
      NUP159 gave the punctate nuclear rim staining characteristic of nucleoporins.
      Immunogold electron microscopy with isolated yeast NEs yielded decoration of only
      the cytoplasmic side of the nuclear pore complex. The gene encoding NUP159 is
      essential, and, like some other nucleoporins, NUP159 contains a coiled-coil
      domain as well as a domain of repeated motifs. Five segments of NUP159, covering
      its entire length, were expressed in Escherichia coli. The repeat motif
      containing segment was found to bind a nuclear transport substrate in the
      presence of vertebrate cytosolic extract containing nuclear transport factors.
      This segment also bound 35S-labeled mammalian karyopherin beta, one such
      transport factor that mediates the docking of substrates to the nuclear pore
      complex. These data establish a direct biochemical link between the repeat motif
      domain of a yeast nucleoporin, transport factors, (specifically karyopherin
      beta), and nuclear transport substrates. Its cytoplasmic aspect implies a role
      for NUP159 in nuclear import.

PMID- 7642563
TI  - Heregulin-stimulated signaling in rat pheochromocytoma cells. Evidence for ErbB3
      interactions with Neu/ErbB2 and p85.
AB  - We have reported that overexpression of Neu leads to heregulin-stimulated neurite
      outgrowth and the tyrosine-phosphorylation of Neu and other cellular proteins in
      PC12 cells. Considering that Neu/ErbB2 alone is not able to functionally couple
      to heregulin, we looked for the possible involvement of ErbB3 in these neurite
      outgrowth and tyrosine phosphorylation responses. We found that heregulin
      stimulates the tyrosine phosphorylation of endogenous ErbB3 protein in PC12 cells
      and that this phosphorylation, like that of Neu, is greatly enhanced in cells
      that overexpress Neu. Furthermore, overexpression of ErbB3 in PC12 cells led to
      heregulin-stimulated neurite extension. In addition to becoming tyrosine
      phosphorylated, Neu/ErbB2 and ErbB3 associate with each other, and each
      associates with the 85-kDa regulatory subunit (p85) of phosphatidylinositol 3
      kinase in a heregulin-dependent manner. Thus, Neu/ErbB2 and ErbB3 appear to
      cooperate to mediate the heregulin signal in PC12 cells. Like heregulin,
      epidermal growth factor (EGF) also stimulate the tyrosine phosphorylation of both
      Neu and ErbB3. However, there are clear differences between the EGF- and
      heregulin-stimulated phosphorylations of ErbB3. In the heregulin response, two
      tyrosine-phosphorylated forms of ErbB3 are detected. Of these, only the more
      quickly migrating form (on SDS-polyacrylamide gel electrophoresis) is found to be
      associated with Neu, whereas the other, more slowly migrating form is uniquely
      capable of forming stable complexes with p85. In the EGF response, at least two
      tyrosine-phosphorylated forms of ErbB3 are detected, but these phosphoproteins
      have distinctly lower apparent molecular weights compared with the heregulin
      stimulated ErbB3 phosphoproteins and do not complex with p85. Thus the formation
      of a stable ErbB3-p85 complex in PC12 cells is a unique outcome of heregulin
      signaling that correlates with the differences in cell morphology induced by the
      activated EGF receptor and the Neu tyrosine kinase.

PMID- 7642564
TI  - The DNA ligands influence the interactions between the herpes simplex virus 1
      origin binding protein and the single strand DNA-binding protein, ICP-8.
AB  - The herpes simplex virus type 1 (HSV-1) origin binding protein, OBP, is a DNA
      helicase specifically stimulated by the viral single strand DNA-binding protein,
      ICP-8. The stimulation is dependent on direct protein-protein interactions
      between the C-terminal domain of OBP, delta OBP, and ICP 8 (Boehmer, P.E.,
      Craigie, M.C., Stow, N.D., and Lehman, I.R. (1994) J. Biol. Chem. 269, 29329
      29334). We have now observed that this interaction is dramatically influenced by
      the nature of the DNA ligand. Stable complexes between delta OBP, ICP 8, and
      double-stranded DNA, presented either as a specific duplex oligonucleotide or a
      restriction fragment containing the HSV-1 origin of replication, oriS, can be
      detected by gel chromatography and gel electrophoresis. In contrast, a single
      stranded oligonucleotide, oligo(dT)65, will completely disrupt the complex
      between delta OBP and ICP 8. We therefore suggest that the interaction between
      delta OBP and ICP 8 serves to position the single strand DNA-binding protein with
      high precision onto single-stranded DNA at a replication fork or at an origin of
      DNA replication.

PMID- 7642565
TI  - Photoreactive analogues of prenyl diphosphates as inhibitors and probes of human
      protein farnesyltransferase and geranylgeranyltransferase type I.
AB  - Photoreactive analogues of prenyl diphosphates have been useful in studying
      prenyltransferases. The effectiveness of analogues with different chain lengths
      as probes of recombinant human protein prenyltransferases is established here. A
      putative geranylgeranyl diphosphate analogue, 2-diazo-3,3,3-trifluoropropionyloxy
      farnesyl diphosphate (DATFP-FPP), was the best inhibitor of both protein
      farnesyltransferase (PFT) and protein geranylgeranyltransferase-I (PFFT-I).
      Shorter photoreactive isprenyl diphosphate analogues with geranyl and
      dimethylallyl moieties and the DATFP-derivative of farnesyl monophosphate were
      much poorer inhibitors. DATFP-FPP was a competitive inhibitor of both PFT and
      PGGT-I with Ki values of 100 and 18 nM, respectively. [32P]DATFP-FPP specifically
      photoradiolabelled the beta-subunits of both PFT and PGGT-I. Photoradiolabelling
      of PGGT-I was inhibited more effectively by geranylgeranyl diphosphate than
      farnesyl diphosphate, whereas photoradiolabelling of PFT was inhibited better by
      farnesyl diphosphate than geranylgeranyl diphosphate. These results lead to the
      conclusions that DATFP-FPP is an effective probe of the prenyl diphosphate
      binding domains of PFT and PGGT-I. Furthermore, the beta-subunits of protein
      prenyltransferases must contribute significantly to the recognition and binding
      of the isoprenoid substrate.

PMID- 7642566
TI  - Insulin-like growth factor I receptor activated by a transmembrane mutation.
AB  - We constructed mutant receptors by mutating transmembrane Val922 of the human
      insulin-like growth factor I receptor (IGF-IR). Assays of receptor kinase and
      autophosphorylation revealed constitutively augmented tyrosine kinase activity of
      V922E IGF-IR in both transient and stable expression. The constitutively active
      tyrosine kinase of this mutant was verified by promoted tyrosine phosphorylation
      of insulin receptor substrate-1 (IRS-1) in the absence of IGF-I. In CHO cells
      stably increasing V922E IGF-IR, both IRS-1 phosphorylation and the IRS-1
      associated phosphoinositide 3-kinase activity were stimulated in the absence of
      IGF-I to the level attained by 1 nM IGF-I stimulation of wild-type IGF-IR,
      whereas the Ras-mitogen-activated protein kinase pathway was not activated under
      the same condition. In these CHO cells, V922E IGF-IR significantly stimulated
      glucose uptake but did not promote mitogenesis in the absence of IGF-I. We thus
      conclude that the V922E mutation of IGF-IR switches on the intrinsic tyrosine
      kinase and differentially activates the downstream pathways. This mutant is
      extremely useful in clarifying the turning-on mechanism of IGF-IR as well as the
      differential roles of individual downstream pathways of receptor tyrosine
      kinases.

PMID- 7642567
TI  - Kinetics of calcium release by immunoaffinity-purified inositol 1,4,5
      trisphosphate receptor in reconstituted lipid vesicles.
AB  - The kinetics of inositol 1,4,5-trisphosphate (IP3)-induced Ca2+ release of the
      immunoaffinity-purified IP3 receptor (IP3R), reconstituted into lipid vesicles,
      was investigated using the fluorescent Ca2+ indicator fluo-3. IP3R was purified
      from mouse cerebellar microsomal fraction by using an immunoaffinity column
      conjugated with an anti-IP3R type 1 (IP3R1) antibody. The immunoblotting analysis
      using monoclonal antibodies against each IP3R type showed that the purified IP3R
      is almost homogeneous, composed of IP3R1. Ca2+ efflux from the proteoliposomes
      was monitored as fluorescence changes of 10 microM fluo-3, whose concentration
      was high enough to buffer released Ca2+ and to keep deviations of extravesicular
      free Ca2+ concentration within 30 nM, excluding the possibility of Ca(2+)
      mediated regulation of IP3-induced Ca2+ release. We also examined IP3-induced
      Ca2+ release using 1 microM fluo-3, where the deviations of free Ca2+
      concentration were within 300 nM. At both fluo-3 concentrations, IP3-induced Ca2+
      release showed similar kinetic properties, i.e. little Ca2+ regulation of Ca2+
      release was observed in this system. IP3-induced Ca2+ release of the purified
      IP3R exhibited positive cooperativity; the Hill coefficient was 1.8 +/- 0.1. The
      half-maximal initial rate for Ca2+ release occurred at 100 nM IP3. At the
      submaximal concentrations of IP3, the purified IP3R showed quantal Ca2+ release,
      indicating that a single type of IP3R is capable of producing the phenomenon of
      quantal Ca2+ of release. The profiles of the IP3-induced Ca2+ release of the
      purified IP3R were found to be biexponential with the fast and slow rate
      constants (k(fast) = 0.3 approximately 0.7 s-1, k(slow) = 0.03 approximately 0.07
      s-1), indicating that IP3R has two states to release CA2+. The amount of released
      Ca2+ by the slow phase was constant over the range of 10-5000 nM IP3
      concentrations, whereas that by the fast phase increased in proportion to added
      IP3. This provides evidence to support the view that the fast phase of Ca2+
      release is mediated by the low affinity state and the slow phase by the high
      affinity state of the IP3R. This also suggests that the fast component of Ca2+
      release is responsible for the process of quantal Ca2+ release.

PMID- 7642568
TI  - The role of the amino-terminal domain and the collagenous region in the structure
      and the function of rat surfactant protein D.
AB  - Surfactant protein D (SP-D) is a member of the C-type lectin superfamily with
      four distinct structural domains: an amino terminus involved in forming
      intermolecular disulfides, a collagen-like domain, a neck region, and a
      carbohydrate recognition domain. A collagen domain deletion mutant (CDM) of SP-D
      was created by site-directed mutagenesis. A second variant lacking both the amino
      terminal region and the collagen-like domain was generated by collagenase
      treatment and purification of the collagenase-resistant fragment (CRF). The CDM
      expressed in CHO-K1 cells formed the covalent trimers, but not the noncovalent
      dodecamers, typical of native SP-D. The CRF derived from recombinant SP-D formed
      only monomers. The CDM bound mannose-Sepharose and phosphatidylinositol (PI) as
      well as SP-D, but the binding to mannosyl bovine serum albumin and
      glucosylceramide was diminished by approximately 60%. The CRF displayed weak
      binding to mannose-Sepharose and PI and essentially no binding to mannosyl bovine
      serum albumin and glucosylceramide. Both SP-D and CDM altered the self
      aggregation of PI-containing liposomes. SP-D reduced the density and the light
      scattering properties of PI aggregates. These results demonstrate that the
      collagen-like domain is required for dodecamer but not covalent trimer formation
      of SP-D and plays an important, but not essential, role in the interaction of SP
      D with PI and GlcCer. Removal of the amino-terminal domain of SP-D along with the
      collagen-like domain diminishes PI binding and effectively eliminates GlcCer
      binding.

PMID- 7642569
TI  - Activation of the STAT pathway by angiotensin II in T3CHO/AT1A cells. Cross-talk
      between angiotensin II and interleukin-6 nuclear signaling.
AB  - We recently reported that angiotensin II (AII), acting through the STAT (Signal
      Transducers and Activators of Transcription) pathway, stimulated a delayed SIF
      (sis-inducing factor)-like DNA binding activity (maximal at 2-3 h) (Bhat, G.J.,
      Thekkumkara, T.J., Thomas, W.G., Conrad, K.M., and Baker, K.M. (1994) J. Biol.
      Chem. 269, 31443-31449). Using a cell line transfected with the AT1A receptor
      (T3CHO/AT1A), we further characterized the AII-induced SIF response and explored
      the possible reasons for the delay in stimulated SIF activity. In cells
      transfected with a chloramphenicol acetyltransferase reporter plasmid, under the
      control of a SIE (sis-inducing element), AII markedly stimulated chloramphenicol
      acetyltransferase activity. The delayed SIF activation by AII was not due to a
      requirement for the release of other SIF inducing factors into the medium and
      contrasts with the rapid (5 min) induction elicited by the cytokine, interleukin
      6 (IL-6). Interestingly, both agents stimulated tyrosine phosphorylation of
      Stat92 and predominantly the formation of SIF complex A. We tested the hypothesis
      that AII initially activated an inhibitory pathway, which was responsible for
      delaying the maximal SIF stimulation until 2 h. Pretreatment of cells for 15 min
      with AII resulted in significant inhibition of the IL-6 induced nuclear SIF
      response (10 min) and Stat92 tyrosine phosphorylation, which was blocked by
      EXP3174, an AT1 receptor antagonist. This inhibition was transient with return of
      the IL-6-induced SIF response at 2 h, suggesting that the delayed maximal
      activation of SIF by AII occurs following an initial transient inhibitory phase.
      Pretreatment of cells with phorbol 12-myristate 13-acetate for 15 min, to
      activate protein kinase C, resulted in inhibition of the IL-6-induced SIF
      response (10 min). However, down-regulation of protein kinase C activity
      prevented phorbol 12-myristate 13-acetate, but not AII mediated inhibition of the
      IL-6-induced SIF response. Although the mechanism is not clear, the results
      presented in this paper raise the interesting possibility that the activation of
      SIF/Stat92 by AII is characterized by an initial inhibitory phase, followed by
      the induction process. The observation that AII and IL-6 utilize similar
      components of the STAT pathway and that AII can cross-talk with IL-6 signaling
      through inhibition of IL-6-induced SIF/Stat92, implies a modulatory role for AII
      in cellular responses to cytokines.

PMID- 7642570
TI  - Assembly/disassembly of the nuclear envelope membrane. Characterization of the
      membrane-chromatin interaction using partially purified regulatory enzymes.
AB  - Assembly and disassembly of the nucleus at mitosis in eukaryotes involves the
      reversible interaction of chromatin with the nuclear membrane. Previously we have
      shown that this interaction is regulated by the antagonistic activities of a
      kinase and a phosphatase. The kinase promotes membrane release while the
      phosphatase stimulates binding. In this report we describe four steps in the
      purification of the kinase needed for release of membranes from chromatin. We
      also show that the release kinase and the mitotic initiation kinase, cdc2, are
      distinct and are separated from each other during the second purification step.
      Reconstitution experiments using these two kinases demonstrate that the release
      kinase and cdc2 kinase work in concert to cause membrane release from chromatin.
      In phosphorylation experiments, protein targets that are substrates for the
      regulatory release kinase are identified on the membranes. These phosphorylated
      proteins ae candidates for regulated proteins mediating membrane-chromatin
      interaction. Finally, we find that membrane release activity can also be
      extracted from membranes by high salt treatment, indicating a possible dual
      localization of this activity.

PMID- 7642571
TI  - Thymidine phosphorylase mediates the sensitivity of human colon carcinoma cells
      to 5-fluorouracil.
AB  - Interferon-alpha (IFN alpha) potentiates the antitumor activity of 5-fluorouracil
      (FUra) in colon cancer in vitro, in vivo, and clinically. A likely mechanism for
      this action is the induction by IFN alpha of thymidine phosphorylase (TP), the
      first enzyme in one pathway for the metabolic activation of FUra to
      fluorodeoxyribonucleotides. To test this hypothesis, an expression vector
      containing the TP cDNA was transfected into HT-29 human colon carcinoma cells.
      Five stable transfectants were selected and analyzed. All showed increased
      sensitivity to FUra cytotoxicity, ranging from a 2-fold to a 19-fold decrease in
      the IC50 for FUra, compared to wild-type cells. Levels of TP mRNA, protein, and
      enzyme activity were elevated in the transfectants, and there was a significant
      correlation between the relative increase in sensitivity to FUra and both the
      increase in both TP mRNA levels and TP activity. Transfected cells exhibited
      increased formation of FdUMP, but not the ribonucleotides FUDP and FUTP, from
      FUra when compared to wild-type cells. The changes in TP activity, FdUMP
      formation, and FUra sensitivity in the transfected cells were comparable with
      those seen after treatment of wild-type cells with IFN alpha. These studies
      provide direct evidence for the role of TP in mediating the sensitivity of colon
      carcinoma cells to FUra, and further support the importance of the induction of
      TP in the biomodulating action of IFN alpha on FUra chemosensitivity.

PMID- 7642572
TI  - The cyclic AMP response elements of the genes for angiotensin converting enzyme
      and phosphoenolpyruvate carboxykinase (GTP) can mediate transcriptional
      activation by CREM tau and CREM alpha.
AB  - The potential of the CREM family of proteins to activate transcription of the
      genes encoding the testis-specific isozyme of angiotensin converting enzyme
      (ACET) and the gluconeogenic enzyme, phosphoenolpyruvate carboxykinase (GTP)
      (PEPCK) (EC 4.1.1.32) were investigated. Both CREM tau and CREM alpha bind
      efficiently to the putative cyclic AMP response element (CRE) present in the ACET
      gene (CRET) and to the CRE in the PEPCK gene. In HepG2 cells, the CRE was
      required for the strong stimulation by CREM tau of the expression of a chimeric
      PEPCK (-210 to +73)-chloramphenicol acetyl transferase (CAT) gene. The CRE could
      be mutated to the CRET sequence without losing the stimulatory effects of CREM
      tau. However, a similar chimeric gene driven by the regulatory region of the ACET
      gene, which contains the CRET site, could only be stimulated by CREM tau when its
      imperfect TATA element was mutated to an authentic TATA. Surprisingly, CREM
      alpha, an alleged inhibitor of CRE-mediated transcription, stimulated the
      expression of both PEPCK-CAT and ACET-CAT genes in HepG2 cells, a process which
      required the presence of the CRE and the CRET sites, respectively. In contrast,
      when the same CRE elements were used to drive the transcription of a chimeric
      gene containing the thymidine kinase promoter linked to the CAT structural gene,
      CREM alpha inhibited its expression in HepG2 and JEG3 cells. The expression of
      the same chimeric gene, however, was stimulated by CREM alpha in F9 embryonal
      carcinoma cells. These results demonstrated that the nature of the
      transcriptional effects of CREM isoforms on CRE-mediated transcription depends on
      the specific gene, the specific cell type and the promoter context of the CRE
      site.

PMID- 7642573
TI  - Junction mobility and resolution of Holliday structures by Flp site-specific
      recombinase. Testing partner compatibility during recombination.
AB  - Absolute homology between partner substrates within the strand exchange region
      (spacer) is an essential requirement for recombination mediated by the yeast site
      specific recombinase Flp. Recent experiments suggest that 3-base pair homology
      adjacent to the points of exchange at each end of the spacer is utilized in a
      base complementarity-dependent strand joining reaction. Homology of the central 2
      base pairs of the spacer is also critical, but how homology is tested at these
      two positions is unknown. We have addressed the role of homology-dependent branch
      migration in Flp recombination by assaying strand cleavage and resolution in a
      set of synthetic Holliday junctions in which the branch point is freely or
      partially mobile through the spacer, or is immobilized at each position within
      the spacer or immediately flanking it. A strong bias in the direction of Holliday
      resolution is observed only when the branch point is located just outside the
      spacer (at the junction of the Flp binding element and the spacer). A
      significantly smaller bias is noticed when the branch point is frozen immediately
      adjacent to this position within the spacer. Resolution in these cases is most
      often mediated by exchange of the scissile phosphodiesters at the branch point or
      proximal to it, and rarely by exchange of the scissile phosphodiesters distal to
      it. In light of these and previous results, we discuss possible checkpoints for
      testing partner compatibility during Flp recombination.

PMID- 7642574
TI  - ACS4, a primary indoleacetic acid-responsive gene encoding 1-aminocyclopropane-1
      carboxylate synthase in Arabidopsis thaliana. Structural characterization,
      expression in Escherichia coli, and expression characteristics in response to
      auxin [corrected].
AB  - 1-Aminocyclopropane-1-carboxylic acid (ACC) synthase is the key regulatory enzyme
      in the biosynthetic pathway of the plant hormone ethylene. The enzyme is encoded
      by a divergent multigene family in Arabidopsis thaliana, comprising at least five
      genes, ACS1-5 (Liang, X., Abel, S., Keller, J.A., Shen,N. N.F., and Theologis, A.
      (1992) Poc. Natl. Acad. Sci. U.S.A. 89, 11046-11050). In etiolated seedlings,
      ACS4 is specifically induced by indoleacetic acid (IAA). The response to IAA is
      rapid (within 25 min) and insensitive to protein synthesis inhibition, suggesting
      that the ACS4 gene expression is a primary response to IAA. The ACS4 mRNA
      accumulation displays a biphasic dose-response curve which is optimal at 10
      microM of IAA. However, IAA concentrations as low as 100 microM are sufficient to
      enhance the basal level of ACS4 mRNA. The expression of ACS4 is defective in the
      Arabidopsis auxin-resistant mutant lines axr1-12, axr2-1, and aux1-7. ACS4 mRNA
      levels are severely reduced in axr1-12 and axr2-1 but are only 1.5-fold lower in
      aux1-7. IAA inducibility is abolished in axr2-1. The ACS4 gene was isolated and
      structurally characterized. The promoter contains four sequence motifs
      reminiscent of functionally defined auxin-responsive cis-elements in the early
      auxin-inducible genes PS-IAA4/5 from pea and GH3 from soybean. Conceptual
      translation of the coding region predicts a protein with a molecular mass of
      53,795 Da and a theoretical isoelectric point of 8.2. The ACS4 polypeptide
      contains the 11 invariant amino acid residues conserved between aminotransferases
      and ACC synthases from various plant species. An ACS4 cDNA was generated by
      reverse transcriptase-polymerase chain reaction, and the authenticity was
      confirmed by expression of ACC synthase activity in Escherichia coli.

PMID- 7642575
TI  - Association between NS3 and NS5 proteins of dengue virus type 2 in the putative
      RNA replicase is linked to differential phosphorylation of NS5.
AB  - Dengue virus type 2, a member of the family Flaviviridae, encodes a single
      polyprotein precursor consisting of 3391 amino acids residues that is processed
      to at least 10 mature proteins by host and viral proteases. The NS3 protein
      contains a domain commonly found in cellular serine proteinases that in
      cooperation with NS2B is involved in polyprotein processing. In addition, NS3 and
      NS5 proteins contain conserved motifs found in several RNA helicases and RNA
      dependent RNA polymerases, respectively. Both enzymatic activities have been
      suggested to be involved in viral RNA replication. In this report, we demonstrate
      that the NS3 and NS5 proteins interact in vivo in dengue virus type 2-infected
      monkey kidney (CV-1) cells and in HeLa cells coinfected with recombinant vaccinia
      viruses encoding these proteins as shown by coimmunoprecipitations and
      immunoblotting methods. We also show by immunofluorescence, metabolic labeling,
      and two-dimensional peptide mapping that NS5 is a nuclear phosphoprotein and that
      phosphorylation occurs on serine residues at multiple sites. Furthermore, NS5
      exists in differentially phosphorylated states in the nuclear and the cytoplasmic
      fractions, and only the cytoplasmic form of NS5 is found to coimmunoprecipitate
      with NS3, suggesting that differential phosphorylation may control the
      interaction between these proteins and its function in the viral RNA replicase.

PMID- 7642576
TI  - Molecular dissection of the role of the membrane domain in the regulated
      degradation of 3-hydroxy-3-methylglutaryl coenzyme A reductase.
AB  - We have previously shown that the membrane domain of 3-hydroxy-3-methylglutaryl
      coenzyme A (HMG-CoA) reductase from hamster contains all of the sequences
      required for both localization to the endoplasmic reticulum and regulated
      degradation of the enzyme. It has been reported that the enzymatic activity and
      mRNA levels of HMG-CoA reductase from sea urchin embryos cultured in the presence
      of regulators were unchanged compared to levels in control embryos (Woodward,
      H.D., Allen, M.C., and Lennarz, W.J. (1988) J. Biol. Chem. 263, 18411-18418).
      This observation led us to investigate the possibility that the sea urchin enzyme
      is not subject to regulated protein turnover. Interestingly, the sea urchin
      enzyme shares 62% amino acid sequence identity with the hamster enzyme in the
      membrane domain and shares similar predicted topological features. In the current
      studies we have compared the degradation phenotypes of the sea urchin HMG-CoA
      reductase and the hamster HMG-CoA reductase in Chinese hamster ovary cells to
      further elucidate the role of the membrane domain in enzyme degradation in
      response to physiological regulators. To accomplish this, we constructed sea
      urchin HMGal (uHMGal), the structural equivalent of hamster HMGal (httMGal),
      which has the sea urchin HMG-CoA reductase membrane domain fused to Escherichia
      coli beta-galactosidase. The uHMGal was stably expressed in CHO cells, and we
      found that the degradation of uHMGal is not accelerated by sterols, and even in
      the absence of sterols, it is less stable than hHMGal. We also constructed
      chimeric hamster/sea urchin HMGal molecules to investigate which amino acid
      sequences from the hamster enzyme are sufficient to confer sterol-regulated
      degradation upon the sea urchin enzyme. Our results identify the second membrane
      spanning domain of hamster enzyme as important for the regulated degradation of
      HMG-CoA reductase.

PMID- 7642577
TI  - Action of alpha-amanitin during pyrophosphorolysis and elongation by RNA
      polymerase II.
AB  - Using defined elongation complexes formed on dC-tailed templates with Drosophila
      RNA polymerase II, we have examined elongation, pyrophosphorolysis, and DmS-II
      mediated transcript cleavage and the inhibitory effect of alpha-amanitin on these
      processes. Analysis of pyrophosphorolysis on soluble or immobilized and templates
      confirmed that NTPs are liberated instead of dinucleotides that are released
      during DmS-II-mediated transcript cleavage. 10 microgram/ml alpha-amanitin
      completely inhibited DmS-II-mediated transcript cleavage but allowed extended
      pyrophosphorolysis and nucleotide addition to occur. alpha-Amanitin dramatically
      decreased the Vmax for nucleotide addition but only slightly affected the Km for
      nucleotides. Although the processes ae mechanistically distinct, both
      pyrophosphorolysis and DmS-II-mediated transcript cleavage frequently resulted in
      similar patterns of shortened transcript. Since polymerase molecules encounter
      similar kinetic barriers during both processes, it is possible that there is a
      common step in the reverse movement of the polymerase.

PMID- 7642578
TI  - The putative amino-terminal signal peptide of the cloned rat brain Na(+)-Ca2+
      exchanger gene (RBE-1) is not mandatory for functional expression.
AB  - The rat brain Na(+)-Ca2+ exchanger (RBE) gene, as well as other isoforms of this
      protein family, can be organized into 12 transmembrane alpha helices, the first
      of which was proposed by Durkin et al. (14) to constitute a cleavable signal
      peptide. We have prepared three amino-terminal mutants, in which 21, 26, and 31
      amino acids beyond the initiating methionine were deleted. The deletions include
      the hydrophobic core of the putative signal peptide (N21), the entire putative
      signal peptide and parts of the putative signal peptidase cleavage site (N26),
      and the entire putative signal peptide and putative signal peptidase cleavage
      site (N31). All three mutant clones were transiently expressed in HeLa cells. The
      average Na+ gradient-dependent Ca2+ transport activity of the mutant exchangers
      was 108% (N21), 37.2% (N26), and 60.06% (N31) of the wild-type clone. Mutation of
      the putative cleavage site by an exchange of Ala-32 --> Asp, resulted in a
      decrease in Na(+)-Ca2+ exchange activity to 7.7%, relative to the wild-type
      exchanger. Functional reconstitution of the proteins that were expressed in the
      transfected cells, resulted in transport activities of: 60.1% (N21), 26.75%
      (N26), 85.36% (N31), and 31% (Ala-32 --> Asp) relative to the wild-type
      exchanger. Western blot analysis of the protein profile of RBE-1, N21, N26, N31
      and Ala-32 --> Asp-transfected HeLa cells was carried out by using an antipeptide
      antibody directed against a pentadecapeptide segment derived from the large
      putative cytoplasmic loop of the cloned rat exchanger gene. In the total cell
      extract and in the plasma membrane-enriched fraction, in addition to a major
      protein band of about 125 kDa, which corresponds to the molecular mass of the
      mature fully processed Na(+)-Ca2+ exchanger, an additional protein of about 135
      kDa is revealed in the profile of N21- and N26-transfected cells. This band is
      not detected in the protein profile of RBE-1, N31, or Ala-32 -->Asp. The amino
      terminal truncated mutants of the cloned Na(+)-Ca2+ exchanger could be expressed
      and processed also in a reticulocyte lysate supplemented with dog microsomes. Our
      results suggest that the putative signal peptide of the cloned Na(+)-Ca2+
      exchanger gene does not play a mandatory role in functional expression of the
      protein in HeLa cells.

PMID- 7642579
TI  - Rat serum carboxylesterase. Cloning, expression, regulation, and evidence of
      secretion from liver.
AB  - Multiple forms of carboxylesterase have been identified in rat liver, and five
      carboxylesterases (designated hydrolases A, B, C, S, and egasyn) have been
      cloned. Hydrolases A, B, C, and egasyn all have a C-terminal consensus sequence
      (HXEL) for retaining proteins in the endoplasmic reticulum, and these
      carboxylesterases are found in rat liver microsomes. In contrast, hydrolase S
      lacks this C-terminal consensus sequence and is presumed to be secreted. In order
      to test this hypothesis, a polyclonal antibody was raised against recombinant
      hydrolase S from cDNA-directed expression in Escherichia coli. In addition to
      hydrolases A, B, and C (57-59 kDa), this antibody recognized a 67-kDa protein in
      rat liver microsomes and a 71-kDa protein in rat serum. The 71-kDa protein
      detected in rat serum was also detected in the extracellular medium from primary
      cultures of rat hepatocytes. Non-denaturing gel electrophoresis with staining for
      esterase activity showed that a serum carboxylesterase comigrated with the 71-kDa
      protein. Immunoprecipitation of the 71-kDa enzyme from rat serum decreased
      esterase activity toward 1-naphthylacetate and para-nitrophenylacetate. The 71
      kDa protein immunoprecipitated from rat serum had an N-terminal amino acid
      sequence identical to that predicted from the cDNA encoding hydrolase S,
      providing further evidence that hydrolase S is synthesized in and secreted by the
      liver. The levels of the 67-kDa protein in rat liver microsomes and the levels of
      the 71-kDa protein in rat serum were co-regulated. Deglycosylation of microsomes
      and serum converted the 67- and 71-kDa proteins to a 58-kDa peptide, which
      matches the molecular mass calculated from the cDNA for hydrolase S. These
      results suggest that the 67-kDa protein in liver microsomes is a precursor form
      of hydrolase S that undergoes further glycosylation before being secreted into
      serum. In rats, liver appears to be the only source of hydrolase S because no
      mRNA encoding hydrolase S could be detected in several extrahepatic tissues.
      Serum carboxylesterases have been found to play an important role in lipid
      metabolism and detoxication of organophosphates, therefore, the secretion of
      hydrolase S and the modulation of its expression by xenobiotics may have
      physiological as well as toxicological significance.

PMID- 7642580
TI  - Processing of the precursors to neurotensin and other bioactive peptides by
      cathepsin E.
AB  - Cathepsin E (EC 3.4.23.34), an intracellular aspartic proteinase, was purified
      from monkey intestine by simple procedures that included affinity chromatography
      and fast protein liquid chromatography. Cathepsin E was very active at weakly
      acidic pH in the processing of chemically synthesized precursors such as the
      precursor to neurotensin/neuromedin, proopiomelanocortin, the precursor to
      xenopsin, and angiotensinogen. The processing sites were adjacent to a dibasic
      motif in the former two precursors and at hydrophobic recognition sites in the
      latter two. The common structural features that specified the processing sites
      were found in the carboxyl-terminal sequences of the active peptide moieties of
      these precursors; namely, the sequence Pro-Xaa-X'aa-hydrophobic amino acid was
      found at positions P4 through P1. Pro at the P4 position is thought to be
      important for directing the processing sites of the various precursor molecules
      to the active site of cathepsin E. Although the positions of Xaa and X'aa were
      occupied by various amino acids, including hydrophobic and aromatic amino acids,
      some of these had a negative effect, as typically observed when Glu/Arg and Pro
      were present at the P3 and P2 positions, respectively. Cathepsin D was much less
      active or was almost inactive in the processing of the precursors to neurotensin
      and related peptides as a result of the inability of the Pro-directed
      conformation of the precursor molecules to gain access to the active site of
      cathepsin D. Thus, the consensus sequence of precursors, Pro-Xaa-X'aa-hydrophobic
      amino acid, might not only generate the best conformation for cleavage by
      cathepsin E but might be responsible for the difference in specificities between
      cathepsins E and D.

PMID- 7642581
TI  - The SH3 domain-binding T cell tyrosyl phosphoprotein p120. Demonstration of its
      identity with the c-cbl protooncogene product and in vivo complexes with Fyn,
      Grb2, and phosphatidylinositol 3-kinase.
AB  - Previously, we have identified p120 as a Fyn/Lck SH3 and SH2 domain-binding
      protein that is tyrosine phosphorylated rapidly after T cell receptor triggering.
      Here, we used direct protein purification, amino acid sequence analysis,
      reactivity with antibodies, and two-dimensional gel analyses to identify p120 as
      the human c-cbl protooncogene product. We demonstrate in vivo complexes of
      p120cbl with Fyn tyrosine kinase, the adaptor protein Grb2, and the p85 subunit
      of phosphatidylinositol (PI) 3-kinase. The association of p120cbl with Fyn and
      the p85 subunit of PI 3-kinase (together with PI 3-kinase activity) was markedly
      increased by T cell activation, consistent with in vitro binding of p120cbl to
      their SH2 as well as SH3 domains. In contrast, a large fraction of p120cbl was
      associated with Grb2 prior to activation, and this association did not change
      upon T cell activation. In vitro, p120cbl interacted with Grb2 exclusively
      through its SH3 domains. These results demonstrate a novel Grb2-p120cbl signaling
      complex in T cells, distinct from the previously analyzed Grb2-Sos complex. The
      association of p120cbl with ubiquitous signaling proteins strongly suggests a
      general signal transducing function for this enigmatic protooncogene with
      established leukemogenic potential but unknown physiological function.

PMID- 7642583
TI  - Biotin synthase from Escherichia coli, an investigation of the low molecular
      weight and protein components required for activity in vitro.
AB  - We have developed a radiochemical method for the measurement of biotin synthase
      activity in vitro. A cell-free extract from an Escherichia coli strain containing
      a cloned bioB (biotin synthase) gene was incubated with [14C]dethiobiotin, which
      was converted to [14C] biotin. The assay was used to identify the low molecular
      weight compounds and two of the proteins that, in addition to the bioB gene
      product, are required for biotin synthase activity in vitro. The low molecular
      weight compounds are cysteine; S-adenosylmethionine; thiamine pyrophosphate;
      Fe2+; a pyridine nucleotide (the most effective being NADPH); and one of the
      amino acids asparagine, aspartate, glutamine, or serine. The proteins ae
      flavodoxin and ferredoxin (flavodoxin)-NADP+ reductase (EC 1.18.1.2). A third
      thiamine pyrophosphate-dependent protein is also required for activity. When the
      cell-free extract was incubated with nonlabeled dethiobiotin and either
      [35S]cysteine or [35S]cystine, 35S was incorporated into biotin, and we present
      further evidence that cysteine, and not S-adenosylmethionine or methionine, is
      the sulfur donor for the biotin synthase reaction.

PMID- 7642582
TI  - Localization of the insulin-like growth factor I receptor binding sites for the
      SH2 domain proteins p85, Syp, and GTPase activating protein.
AB  - Potential signaling substrates for the insulin-like growth factor I (IGF-I)
      receptor are SH2 domain proteins including the p85 subunit of
      phosphatidylinositol 3-kinase, the tyrosine phosphatase Syp, GTPase activating
      protein (GAP), and phospholipase C-gamma (PLC-gamma). In this study, we
      demonstrate an association between the IGF-I receptor and p85, Syp, and GAP, but
      not with PLC-gamma in lysates of cells overexpressing the human IGF-I receptor.
      We further investigated these interactions using glutathione S-transferase (GST)
      fusion proteins containing the amino-terminal SH2 domains of p85 or GAP, or both
      SH2 domains of Syp or PLC-gamma to precipitate the IGF-I receptor from purified
      receptor preparations and from whole cell lysates. p85-, Syp-, and GAP-GSTs
      precipitated the IGF-I receptor, whereas the PLC-gamma-GST did not. Using
      phosphopeptides corresponding to IGF-I receptor phosphorylation sites, we
      determined that the p85- and Syp-GST association with the IGF-I receptor could be
      inhibited by a carboxyl-terminal peptide containing pY1316 and that the GAP-GST
      association could be inhibited by a NPXY domain peptide. The GAP-GST binding site
      was confirmed by showing that a mutant IGF-I receptor with a deletion of the NPXY
      domain including tyrosine 950 was poorly precipitated by the GAP-GST. We conclude
      that p85 and Syp may bind directly to the IGF-I receptor at tyrosine 1316, and
      that GAP may bind to the IGF-I receptor at and PLC-gamma was not evident. p85,
      Syp, and GAP are potential modulators of IGF-I receptor signal transduction.

PMID- 7642584
TI  - Identification of the major phosphorylation sites in human C5a anaphylatoxin
      receptor in vivo.
AB  - Interaction of human C5a anaphylatoxin with cell surface receptors mediates cell
      activation and receptor desensitization. Treatment of differentiated HL60 cells
      or transiently transfected COS-7 cells with C5a or phorbol 12-myristate 12
      acetate (PMA) results in rapid hyperphosphorylation of the C5aR. In an attempt to
      gain more insight into the function of phosphorylation in the desensitization of
      C5aR, we have initiated experiments to identify phosphoacceptor sites at the
      amino acid level after stimulation of cells with either C5a or PMA. In this
      report we show that C5aR is phosphorylated exclusively on serine residues in both
      differentiated HL60 and transfected COS-7 cells irrespective of the stimulus
      used. Peptide mapping after cyanogen bromide cleavage of phosphorylated C5aR
      indicates that despite the presence of a protein kinase C consensus motif the
      third cytoplasmic loop is not phosphorylated when cells are challenged with
      either C5a or PMA. Thus, whether the cells are stimulated with C5a or PMA, the
      phosphorylation sites appear to be restricted to serine residues in the carboxyl
      tail. Phosphoamino acid analysis of a series of mutants in which an individual
      serine residue was replaced by a threonine residue indicates that the C5aR
      undergoes C5a-dependent phosphorylation to the maximal stoichiometry of 6 mol of
      PO4/mol of receptor at Ser314, Ser317, Ser327, Ser332, Ser334, and Ser338.
      Simultaneous substitution of serine residues by alanine at positions 332, 334,
      and 338 affected neither the binding of C5a nor the cell surface expression of
      the mutant, but resulted in a dramatic reduction (more than 80%) of both C5a- and
      PMA-mediated phosphorylation as compared to the wild type receptor. This result
      suggests that phosphorylation on the segment extending from Ser332 to Ser338 is
      required for the subsequent phosphorylation of the carboxyl-terminal tail of
      C5aR.

PMID- 7642585
TI  - Truncated forms of the human prion protein in normal brain and in prion diseases.
AB  - The cellular form of the prion protein (PrPc) is a glycoprotein anchored to the
      cell membrane by a glycosylphosphatidylinositol moiety. An aberrant form of PrPc
      that is partially resistant to proteases, PrPres, is a hallmark of prion
      diseases, which in humans include Cruetzfeldt-Jakob disease (CJD), Gerstmann
      Straussler-Scheinker syndrome, and fatal familial insomnia. We have characterized
      the major forms of PrP in normal and pathological human brains. A COOH-terminal
      fragment of PrPc, designated C1, is abundant in normal and CJD brains as well as
      in human neuroblastoma cells. Sequence analysis revealed that C1 contains
      alternative NH2 termini starting at His-111 or Met-112. Like PrPc, C1 is
      glycosylated, anchored to the cell membrane, and is heat-stable. Consistent with
      the lack of the NH2-terminal region of PrPc, C1 is more acidic than PrPc and does
      not bind heparin. An additional fragment longer than C1, designated C2, is
      present in substantial amounts in CJD brains. Like PrPres, C2 is resistant to
      proteases and is detergent-insoluble. Our data indicate that C1 is a major
      product of normal PrPc metabolism, generated by a cleavage that disrupts the
      neurotoxic and amyloidogenic region of PrP comprising residues 106-126. This
      region remains intact in C2, suggesting a role for C2 in prion diseases.

PMID- 7642586
TI  - Irradiation induces WAF1 expression through a p53-independent pathway in KG-1
      cells.
AB  - WAF1 binds to cyclin-Cdk complexes and inhibits their activity, causing cell
      cycle arrest. Previous studies have shown that expression of WAF1 is induced
      through the p53-dependent pathway; WAF1 is induced in cells with functional p53
      but not in cells with either mutant p53 or no 53. Human myeloblastic leukemia
      cells KG-1 had no constitutive expression of p53, and irradiation did not induce
      p53. However, irradiation increased WAF1 expression in KG-1 cells and other cell
      lines containing mutant p53. The KG-1 cells constitutively produced low levels of
      tumor necrosis factor (TNF); irradiation markedly increased the production of
      TNF. Notably, induction of WAF1 mRNA by irradiation was blocked by anti-TNF
      antibody. Furthermore, exogenously added TNF increased levels of WAF1 mRNA in
      these cells. Irradiation increased the rate of WAF1 transcription 3-fold, and the
      half-life (t1/2) of WAF1 mRNA in these cells increased from < 1 h in unirradiated
      cells to > 4 h in irradiated cells. These findings indicate that increased levels
      of WAF1 transcripts occur, at least in part, through a pathway of TNF production
      and that the increase in WAF1 mRNA observed after irradiation is regulated by
      both transcriptional and posttranscriptional mechanisms. Our present study
      strongly suggests that an alternative pathway of induction of WAF1 occurs
      independent of activation by p53.

PMID- 7642587
TI  - Biosynthetic processing of neu differentiation factor. Glycosylation trafficking,
      and regulated cleavage from the cell surface.
AB  - new differentiation factor (NDF), also known as heregulin, is structurally
      related to the epidermal growth factor family of growth factors; it stimulates
      tyrosine phosphorylation of the neu/HER-2 oncogene and causes differentiation of
      certain human breast cancer cell lines. Alternative splicing of a single gene
      gives rise to multiple isoforms of NDF/heregulin, as well as the neuronal
      homologues, designated ARIA (acetylcholine receptor inducing activity) and GGF
      (glial growth factor); at least 15 structural variants are known. All but two of
      the NDF/heregulin cDNAs are predicted to encode transmembrane, glycosylated
      precursors of soluble NDF. In this report we characterized the biosynthetic
      processing of different NDF isoforms in stably transfected Chinese hamster ovary
      cells expressing individual NDF isoforms, and in the native cell line Rat 1-EJ,
      which expresses at least six different NDF isoforms. We found that the precursors
      for NDF undergo typical glycosylation and trafficking. A portion of the molecules
      are proteolytically cleaved intracellularly leading to the constitutive secretion
      of soluble, mature NDF into the culture media. However, a significant portion of
      the newly synthesized NDF precursor molecules escape intracellular cleavage and
      are transported to the cell surface of both transfected and native cells, where
      they reside as full-length, transmembrane proteins. Finally we show that these
      full-length, transmembrane NDF molecules can undergo phorbol ester regulated
      cleavage from the membrane, releasing the soluble growth factor into the medium.

PMID- 7642588
TI  - Prion protein isoforms, a convergence of biological and structural
      investigations.

PMID- 7642589
TI  - A novel transcriptional activator originating from an upstream promoter in human
      growth hormone gene.
AB  - Transcription of the human growth hormone gene can start in vitro and in vivo 197
      base pairs upstream from the cap site of growth hormone mRNA (Courtois, S. J.,
      Lafontaine, D., and Rousseau, G. G. (1992) J. Biol. Chem. 267, 19736-19743). We
      have now characterized the mRNA that originates from this optional promoter and
      have found that it occurs in human hypophysis and placenta but not in 10 other
      tissues. This mRNA contains an open reading frame for a protein of 107 residues
      that shares sequence similarity with three domains of hepatic nuclear factor
      1alpha. With antibodies directed against a peptide corresponding to the C
      terminus of this protein, immunoreactive material was detected in a subset of
      cells of the adenohypophysis. When fused to the DNA-binding domain of the yeast
      transcription factor GAL4, the protein stimulated transcription from a GAL4
      sensitive reporter gene in transiently transfected pituitary and placental cells.

PMID- 7642590
TI  - The molybdenum centers of xanthine oxidase and xanthine dehydrogenase.
      Determination of the spectral change associated with reduction from the Mo(VI) to
      the Mo(IV) state.
AB  - The UV-visible absorbance change associated with reduction of the molybdenum
      centers of xanthine oxidase and xanthine dehydrogenase has been determined using
      a double-difference technique. At pH 8.5, the Mo(VI) minus Mo(IV) difference
      spectrum seen with xanthine oxidase exhibits a positive feature at 420 nm, having
      an extinction change of approximately 3,000 M-1 cm-1 as well as evidence for a
      negative feature below 340 nm. In xanthine oxidase this change is found to
      exhibit a marked pH dependence, implicating protonation/deprotonation events
      associated with changes in the molybdenum oxidation state. Application of the
      double-difference protocol to the respective circular dichroism spectra of
      xanthine oxidase and xanthine dehydrogenase reveals appreciable CD changes at 420
      and 580 nm associated with the reduction of the molybdenum center. The present
      results demonstrate a direct spectroscopic handle on the molybdenum centers of
      both xanthine oxidase and xanthine dehydrogenase.

PMID- 7642591
TI  - Evidence for contact between the cyclic AMP receptor protein and the delta 70
      subunit of Escherichia coli RNA polymerase.
AB  - The loop at the 52-position of the cAMP receptor protein (CRP) has been suggested
      as a potential site for contacting RNA polymerase on Class II promoters where the
      CRP binding site is located at position -41.5 (Bell, A., Gaston, K., Williams,
      R., Chapman, K., Kolb, A., Buc, H., Minchin, S., Williams, J., and Busby, S.
      (1990) Nucleic Acids Res. 18, 7243-7250). Using protein-protein photo-cross
      linking, evidence is presented showing that the 52-loop of CRP is in physical
      proximity to the delta subunit of RNA polymerase holoenzyme. This interaction
      required the presence of a functional preinitiation complex. The CRP suppressor
      mutation, K52N, increased the efficiency of cross-linking, indicating an improved
      physical interaction between the CRP 52-loop and the delta subunit. Evidence for
      direct interaction between the CRP 156-162 loop and delta subunit of RNA
      polymerase on both gal and lac promoters are also provided. The data indicate
      that CRP bound to the gal promoter contacts both the alpha and delta 70 subunits
      of RNA polymerase.

PMID- 7642592
TI  - Factor V is complexed with multimerin in resting platelet lysates and colocalizes
      with multimerin in platelet alpha-granules.
AB  - Factor V stored in platelets is an important source of factor Va for the
      prothrombinase complex. Investigations of potential platelet factor Va-binding
      proteins, using factor Va light chain affinity chromatography, identified a
      disulfide-linked multimeric protein with a reduced mobility of 155 kDa in the
      column eluate. Immunodepletion and immunoblotting indicated that this protein was
      multimerin. Multimerin specifically bound factors V and Va and the isolated
      factor Va light chain, but not the heavy chain of factor Va. Factor V stored in
      platelets, but not plasma factor V, was found to be complexed with multimerin.
      Multimerin immunodepletion of resting platelet lysates was associated with the
      removal of factor V and the loss of factor V coagulant activity. Immunoelectron
      microscopic studies colocalized factor V with multimerin in the alpha-granules of
      resting platelets. With thrombin-induced platelet activation, we observed
      dissociation of factor Va-multimerin complexes, multimerin-independent membrane
      binding of factor Va, and prothrombinase activity that was not inhibitable by
      multimerin antibodies. This study indicates that platelet factor V is stored as a
      complex with multimerin and suggests a possible role for multimerin as a carrier
      protein for factor V stored in platelets.

PMID- 7642593
TI  - Fluorescent peptidyl substrates as an aid in studying the substrate specificity
      of human prohormone convertase PC1 and human furin and designing a potent
      irreversible inhibitor.
AB  - The substrate specificities of two human prohormone convertases, furin and PC1,
      were examined with a series of 7-amino-4-methylcoumarinamide (MCA) containing
      peptidyl substrates. Using acetyl-Arg-Ser-Lys-Arg-MCA as model, P4 Arg
      substitution by Lys or Orn resulted for furin in a 538- and a 280-fold lower
      kcat/Km value, but only in a 14- and 18-fold decrease for PC1. Substitution of P3
      Ser by either Pro, Glu, or Lys does not modify significantly the kcat/Km value
      for PC1, whereas furin activity is seriously impaired by the Glu substitution.
      Elongating the peptidyl sequence up to the P8 position decreases the kcat/Km
      value for furin but not for PC1. In both the P3 or P5 Glu substitution, the
      decrease of kcat/Km was due primarily to lower kcat rather than higher Km,
      possibly because of the presence of a negatively charged side chain. Finally, an
      octapeptidyl chloromethane derivative proved to be a potent irreversible
      inhibitor of either PC1 and ruin. The 811-fold difference in the apparent
      Kapp/[I] (1.63 x 10(6) s-1 m-1), and kcat/Km determined with the corresponding
      peptidyl MCA substrate (2.01 x 10(3) s-1 m-1), supports the proposal that
      cleavage of the acylenzyme represents the rate-limiting step for PC1 and furin.

PMID- 7642594
TI  - Heme-protein interactions in horse heart myoglobin at neutral pH and exposed to
      acid investigated by time-resolved fluorescence in the pico- to nanosecond time
      range.
AB  - We measured the steady state and time-resolved emission intensity decay of horse
      heart myoglobin at various pH values from neutral to pH 4.42. The steady state
      intensity was reversibly increased with the decreasing pH, almost doubling at pH
      4.5. Frequency domain data for emission decay were analyzed separately for each
      pH and simultaneously by global analyses. The results indicated the presence of
      four lifetime components, conserved throughout the pH titrations at 40, 116,
      1363, and 4822 ps, respectively. The titration affected only their fractional
      intensities. Assignments of the lifetimes were based on the Forster theory of
      radiationless dipole-dipole interaction and the atomic coordinates of the system.
      We assigned the two shorter lifetimes to Trp-14 and Trp-7, respectively, in the
      presence of normal hemes. The 1363-ps lifetime was assigned to Trp-7 with
      inverted hemes (i.e. rotated 180 degrees around the alpha-gamma-meso axis of the
      porphyrin ring). The 4822-ns lifetime was assigned to reversibly heme-dissociated
      myoglobin. Lorentzian lifetime distributions were narrow for the lifetimes at 40,
      116, and 4822 ps, indicating a homogeneous protein structure. Instead the
      lifetime at 1363 ns had a broad, pH-independent distribution consistent with
      small angle wobblings of inverted hemes inside the heme pocket. These analyses
      revealed the presence of three species originating from heme-protein
      interactions: the native form of crystalline myoglobin, the conformation with
      disorder hemes, and the reversibly dissociated heme-free myoglobin. There was
      increased heme inversion and heme dissociability at lower pH, consistent with the
      titration of the proximal and distal histidines inside the heme pocket.

PMID- 7642595
TI  - Permeation properties and differential expression across the auditory receptor
      epithelium of an inward rectifier K+ channel cloned from the chick inner ear.
AB  - The auditory receptor epithelium is an excellent model system for studying the
      differential expression of ion channel genes. An inward rectifier potassium
      current is among those which have been measured in only subsets of chick cochlear
      hair cells. We have cloned and characterized an inward rectifier potassium
      channel (cIRK1) from the chick cochlear sensory epithelium. cIRK1 functional
      properties are similar to those of the native channel, and the transcript
      encoding cIRK1 is limited to the low frequency half of the epithelium. This
      localization is in agreement with the distribution of the native hair cell
      current, suggesting that the differential current expression is transcriptionally
      regulated. The primary structure of cIRK1 is highly homologous to the mouse
      inward rectifier IRK1. However, we found that cIRK1 exhibited reduced single
      channel conductance (17 picosiemens) and lower sensitivity to Ba2+ block (K1/2 =
      12 microM). We identified Gln-125 near the putative pore region as being
      responsible for these differences. Site-directed mutagenesis was used to change
      Gln-125 to Glu (the residue in IRK1), resulting in a channel with a single
      channel conductance of 28 picosiemens and a Ba2+ block of K1/2 = 2 microM. We
      propose that Gln-125 may form part of the external vestibule of the pore.

PMID- 7642596
TI  - Demonstration that mammalian methionine synthases are predominantly cobalamin
      loaded.
AB  - Methionine synthase is an important cellular housekeeping enzyme and is dependent
      on the cofactor cobalamin, a derivative of vitamin B12, for activity. It
      functions in two major metabolic pathways including the tetrahydrofolate
      dependent one-carbon cycle and the salvage pathway for methionine. Its
      dysfunction has several physiological ramifications and leads to the development
      of megaloblastic anemia. In addition, it is suspected to be involved in the
      pathogenesis of neural tube defects. An issue that is central in weighing
      therapeutic options for methionine synthase-related disorders is the extent to
      which the enzyme exists as apoenzyme in vivo and, thus, can be potentially
      responsive to vitamin B12 therapy. despite the importance of this issue, the
      extent of holo- versus apoenzyme in mammalian tissue is controversial and
      unresolved. To address this question, we have developed a convenient anaerobic
      assay that employs titanium citrate to deliver low potential electron
      equivalents. The reductive activation of this enzyme is essential under in vitro
      assay conditions. We find that both the human placental and porcine liver
      methionine synthases exist predominantly in the holoenzyme form (90-100%) in the
      crude homogenate. In addition, the activity of the pure enzyme measured in the
      titanium citrate assay is also independent of exogenous cofactor, revealing that
      the cobalamin is tightly bound to the active site.

PMID- 7642597
TI  - Polymerization of hemoglobin S. Quinary interactions of Glu-43(beta).
AB  - Hemoglobin S (HbS) Hoshida and three substituted forms of HbS Hoshida (the
      substituents being on the amide nitrogen of Gln-43(beta) have been prepared by
      the amidation of Glu-43(beta) of HbS with ammonia, methylamine, glycine ethyl
      ester, and galactosamine. The O2 affinity of HbS is increased slightly on
      amidation of Glu-43(beta). All the four amidated derivatives exhibited nearly the
      same oxygen affinity. On the other hand, the influence of amidation on the
      solubility exhibits some sensitivity to the chemical nature of the substituent on
      the Gln-43(beta). The solubility of HbS Hoshida (a case with no substitution on
      Gln-43(beta), and the methyl-substituted derivatives are about 33 and 36% higher
      than that of HbS. The solubility of the HbS modified with the glycine ethyl ester
      or galactosamine is increased to 41 and 47%, respectively. The first derivative
      UV spectra of HbS Hoshida and its methyl derivative reflect very little
      perturbations in their alpha 1 beta 2 interface as compared with that of HbS,
      whereas the amidated derivatives with larger substituents on Gln-43(beta)
      reflected noticeable difference. Thus, the increase in the solubility and the
      oxygen affinity of HbS on the amidation of Glu-43(beta) is primarily a
      consequence of the loss of the negative charge at 43(beta), a residue proximal to
      the alpha 1 beta 2 interface. The copolymerization studies of amidated HbS with
      HbA, and HbS with amidated HbA demonstrate that cis Glu-43(beta) is the "active"
      residue. This assignment is discrepant with the earlier implication of a trans
      configuration for this residue in the polymer (Edelstein, S. J. (1981) J. Mol.
      Biol. 150, 557-575). However, it is consistent with the solution studies of Nagel
      et al. (Nagel, R. L., Bookchin, R. M., Johnson, J., Labie, D., Wajcman, H..,
      Isaac-Sodeye, W. A., Honig, G. R., Schiliro, G., Crookstan, J. H., and Matsutomo,
      K. (1979) Proc. Nat. Acad. Sci. U.S.A. 76, 670-672) and McCurdy et al. (McCurdy,
      P. R., Lorkin, P. A., Casey, R., Lehmann, H., Uddin, D. E., and Dickson, L. G.
      (1974) Am. J. Med. 57, 665-760).

PMID- 7642598
TI  - Mapping the cell binding site on high molecular weight kininogen domain 5.
AB  - Investigations mapped the region(s) on the light chain of high molecular weight
      kininogen (HK) that participates in cell binding. Sequential and overlapping
      peptides of domain 5 (D5H) were synthesized to determine its cell binding
      site(s). Three peptides from non-overlapping regions on D5H were found to inhibit
      biotin-HK binding to endothelial cells. Peptides GKE19 and HNL 21 weakly
      inhibited biotin-HK binding with IC50 of 792 and 215 microM, respectively.
      Peptide HKH20 inhibited biotin-HK binding with an IC50 of 0.2 microM. Two
      peptides, GGH18 and HVL24, which overlapped HKH20, also inhibited biotin-HK
      binding to endothelial cells with IC50 values of 108 and 0.8 microM,
      respectively. Biotinylated HKH20 directly bound to endothelial cells. HK and
      HKH20 bound at or near the same site on endothelial cells because HK inhibited
      biotin-HKH20 binding (IC50 = 0.2 microM). A polyclonal anti-HKH20 antibody also
      blocked biotin-HK binding. Peptides HKH20 and HVL24 and anti-HKH20 antibody also
      inhibited the procoagulant activity of plasma HK. These data indicated that the
      cell and artificial surface binding sites on D5H overlap. The orientation of HK
      on endothelial cells may be critical for the assembly and activation of contact
      system enzymes and the expression of kininogen's anti-thrombin activity.

PMID- 7642599
TI  - An electrophysiological study of yeast mitochondria. Evidence for two inner
      membrane anion channels sensitive to ATP.
AB  - The inner membrane of mitochondria from various strains of Saccharomyces
      cerevisiae has been analyzed with the patch clamp technique for comparison with
      the better known homologous membrane in mammals (Sorgato, M. C., and Moran, O.
      (1993) CRC Crit. Rev. Biochem. Mol. Biol. 18, 127-171). Differently than in
      mammals, the yeast inner membrane was found to harbor essentially two channels
      with similar anionic selectivity but otherwise different functional behavior. One
      had a conductance of around 45 picosiemens (in symmetrical 150 mM KCl) and an
      activity only marginally sensitive to voltage. The other channel was prominent
      for the higher outwardly rectifying current and for the dependence upon voltage
      of the open probability that induced rapid closure at physiological (negative)
      membrane potentials. Particularly interesting was the effect of ATP (Mg2+ free)
      added on the matrix side of the membrane. In the case of the lower conducting
      channel, the nucleotide caused an immediate block of activity (IC50, 0.240 mM),
      whereas it locked the larger conductance in the open state at both positive and
      negative potentials. In proteoliposomes containing both mitochondrial membranes,
      the small conductance was clearly evident, whereas a larger channel, cationic and
      without the voltage dependence typical of that in the native inner membrane, was
      found.

PMID- 7642600
TI  - Induction of the acyl-coenzyme A synthetase gene by fibrates and fatty acids is
      mediated by a peroxisome proliferator response element in the C promoter.
AB  - The long-chain acyl-coenzyme A synthetase (ACS) gene gives rise to three
      transcripts containing different first exons preceded by specific regulatory
      regions A, B, and C. Exon-specific oligonucleotide hybridization indicated that
      only A-ACS mRNA is expressed in rat liver. Fibrate administration induced liver C
      ACS strongly and A-ACS mRNA to a lesser extent. B-ACS mRNA remained undetectable.
      In primary rat hepatocytes and Fa-32 hepatoma cells C-ACS mRNA increased after
      treatment with fenofibric acid, alpha-bromopalmitate, tetradecylthioacetic acid,
      or alpha-linolenic acid. Nuclear run-on experiments indicated that fenofibric
      acid and alpha-bromopalmitate act at the transcriptional level. Transient
      transfections showed a 3.4-, 2.3-, and 2.2-fold induction of C-ACS promoter
      activity after fenofibric acid, alpha-bromopalmitate, and tetradecylthioacetic
      acid, respectively. Unilateral deletion and site-directed mutagenesis identified
      a peroxisome proliferator activator receptor (PPAR)-responsive element (PPRE)
      mediating the responsiveness to fibrates and fatty acids. This ACS PPRE contains
      three imperfect half sites spaced by 1 and 3 oligonucleotides and binds
      PPAR.retinoid X receptor heterodimers in gel retardation assays. In conclusion,
      the regulation of C-ACS mRNA expression by fibrates and fatty acids is mediated
      by PPAR.retinoid X receptor heterodimers interacting through a PPRE in the C-ACS
      promoters. PPAR therefore occupies a key position in the transcriptional control
      of a pivotal enzyme controlling the channeling of fatty acids into various
      metabolic pathways.

PMID- 7642601
TI  - The DvA-1 polyprotein of the parasitic nematode Dictyocaulus viviparus. A small
      helix-rich lipid-binding protein.
AB  - DNA encoding a single unit of the DvA-1 polyprotein of the parasitic nematode
      Dictyocaulus viviparus was isolated and the polypeptide ("rDvA-1L") expressed in
      Escherichia coli, to give a protein showing high binding affinity for fatty acids
      and retinoids. Fluorescent fatty acid probes show substantial changes in emission
      spectrum in the presence of rDvA-1L, which can be reversed by fatty acids (oleic,
      palmitic, stearic, arachidonic) and retinoids, but not by tryptophan, squalene,
      or cholesterol. Moreover, changes in intrinsic fluorescence of retinol or
      retinoic acid confirm a retinoid binding activity. Fluorescence titration
      experiments indicate stoichiometric binding to a single protein site per monomer
      unit with affinities (Kd) in the range 3 x 10(-8) M for 11-((5
      dimethylaminonaphthalene-1-sulfonyl)amino)undecanoic acid, and by competition, 5
      x 10(-8) M for oleic acid. The extreme blue shift of bound fluorescent fatty acid
      suggests an unusually low polarity for the protein binding site. The emission
      spectrum of the single tryptophan of rDvA-1L indicates that it is deeply buried
      in a nonpolar environment, and its spectrum is unaffected by ligand binding. Far
      UV circular dichroism of rDvA-1L reveals a high alpha-helix content (53%).
      Differential scanning calorimetry studies indicate that rDvA-1L is highly stable
      (T(m) approximately 98 degrees C), refolding efficiently following thermal
      denaturation. DvA-1 therefore represents an example of a new class of lipid
      binding protein, and is the first product of a polyprotein with this activity to
      be described.

PMID- 7642602
TI  - Formation of stable inhibitory complexes of myosin subfragment 1 using
      fluoroscandium anions.
AB  - Evidence is presented that MgADP can be noncovalently trapped in myosin
      subfragment 1 in the presence of ScFx resulting in the concomitant loss of ATPase
      function. The rate of inactivation in the presence of MgCl2 at 25 degrees C is
      8.7 M-1 s-1 which is too slow for a simple collisional mechanism and suggests
      that a subsequent slow isomerization step is responsible for formation of a
      stable tenary complex, S1.MgADP.ScFx in a manner analogous to that proposed for
      the Vi stabilized complex by Goodno (Goodno, C. C. (1979) Proc. Natl. Acad. Sci.
      U.S.A. 76, 2620-2624). It is also found that ADP can be trapped in subfragment 1
      in the absence of MgCl2 indicating the formation of an S1.ADP.ScFx complex. The
      stability of these complexes at 4 degrees C was studied by following the loss of
      trapped [14C]ADP with a chase with ADP. The rate of nucleotide loss at 4 degrees
      C was biphasic for both complexes suggesting that the inhibitory complexes exist
      in two distinct states as previously proposed for the ternary complex stabilized
      by Vi (Mihashi, K., Ooi, A., and Hiratsuka, T. (1990) J. Biochem. (Tokyo) 107,
      464-469). Formation of these complexes resulted in a marked enhancement of the
      intrinsic tryptophyl fluorescence suggesting that conformationally they may
      resemble the steady-state intermediate formed with MgATP. The failure to observe
      photolysis in the presence of excess Vi at sites associated with the ATP
      consensus sequence suggests that in these complexes ScFx occupies the site
      responsible for these cleavage reactions and that it is not displaced by the
      added Vi.

PMID- 7642603
TI  - The functional role of the domains of troponin-C investigated with thrombin
      fragments of troponin-C reconstituted into skinned muscle fibers.
AB  - Proteolysis of rabbit fast skeletal troponin-C (RSTnC) with thrombin produces
      four separate fragments containing the following Ca2+-binding site(s): TH1
      (residues 1-120) sites I-III; TH2 (121-159) site IV; TH3 (1-100) sites I and II;
      and TH4 (101-120) site III. We studied the ability of these fragments to restore
      the steady state isometric force in TnC-depleted skinned skeletal muscle fibers.
      Interestingly, we found that all investigated fragments of RSTnC possessed some
      of the properties of native RSTnC, but none of them could fully regulate
      contraction in the fibers like intact RSTnC. TH1 was the most effective in the
      force restoration (65%) whereas the smaller fragments developed about 50% (TH3
      and TH4) or 20% (TH2) of the initial force of unextracted fibers. Additionally,
      much higher concentrations of TH2, TH3, and TH4 compared to RSTnC OR TH1 were
      necessary for force development suggesting a decreased affinity of these
      fragments to their binding site(s) in the fibers. Like intact RSTnC, TH1 was able
      to interact with the fibers in a Ca(2+)-independent (Mg(2+)-dependent) manner,
      indicating that at a minimum, Ca(2+)-binding site III is required for this type
      of binding. The initial binding of the other fragments to the TnC-depleted fibers
      occurred only in the presence of Ca2+. TH2 and TH4 appeared to bind to two
      different binding sites in the fibers. The binding to one of the sites caused
      partial force restoration. This binding of TH2 and TH4 was abolished when Ca2+
      was removed. TH2 and TH4 binding to the second site required Ca2+ initially but
      was maintained in the presence of Mg2+. This interaction of TH2 and TH4 partially
      blocked the rebinding of RSTnC to the fibers. The latter results suggest that
      site III and IV in these small fragments, when removed from the constraints of
      the parent protein, may assume conformations that allow them to function, to a
      certain extent, like both the regulatory sites (I and II) and the Ca(2+)-Mg2+
      sites(III and IV) of TnC.

PMID- 7642604
TI  - The affinity of pyridoxal 5'-phosphate for folding intermediates of Escherichia
      coli serine hydroxymethyltransferase.
AB  - Escherichia coli serine hydroxymethyltransferase is a 94-kDa homodimer. Each
      subunit contains a covalently attached pyridoxal-P, which is required for
      catalytic activity. At which step pyridoxal-P binds in the folding pathway of E.
      coli serine hydroxymethyltransferase is addressed in this study. E. coli serine
      hydroxymethyl-transferase is rapidly unfolded to an apparent random coil in 8 M
      urea. Removal of the urea initiates a complete refolding to the native holoenzyme
      in less than 10 min at 30 degrees C. Several intermediates on the folding pathway
      have been identified. The most important information was obtained during folding
      studies at 4 degrees C. At this temperature, the far-UV circular dichroism
      spectrum and the fluorescence spectrum of the 3 tryptophan residues become
      characteristic of the native apoenzyme in less than 10 min. Size exclusion
      chromatography shows that under these conditions the refolding enzyme is a
      mixture of monomeric and dimeric species. Continued incubation at 4 degrees C for
      60 min results in the formation of only a dimeric species. Neither the monomer
      nor dimer formed at 4 degrees C bind pyridoxal phosphate. Raising the temperature
      to 30 degrees C results in the formation of a dimeric enzyme which rapidly binds
      pyridoxal phosphate forming active enzyme. These studies support the
      interpretation that pyridoxal phosphate binds only at the end of the folding
      pathway to dimeric apoenzyme and plays no significant role in the folding
      mechanism.

PMID- 7642605
TI  - Divergent effects of ATP on the binding of the DnaK and DnaJ chaperones to each
      other, or to their various native and denatured protein substrates.
AB  - Using the native proteins lambda P, lambda O, delta 32, and RepA, as well as
      permanently unfolded alpha-carboxymethylated lactalbumin, we show that DnaK and
      DnaJ molecular chaperones possess differential affinity toward these protein
      substrates. In this paper we present evidence that the DnaK protein binds not
      only to short hydrophobic peptides, which are in an extended conformation, but
      also efficiently recognizes large native proteins (RepA, lambda P). The best
      substrate for either the DnaK or DnaJ chaperone is the native P1 coded
      replication RepA protein. The native delta 32 transcription factor binds more
      efficiently to DnaJ than to DnaK, whereas unfolded alpha-carboxymethylated
      lactalbumin or native lambda P binds more efficiently to DnaK than to the DnaJ
      molecular chaperone. The presence of nucleotides does not change the DnaJ
      affinity to any of the tested protein substrates. In the case of DnaK, the
      presence of ATP inhibits, while a nonhydrolyzable ATP analogues markedly
      stimulates the binding of DnaK to all of these various protein substrates. ADP
      has no effect on these reactions. In contrast to substrate protein binding, DnaK
      binds to the DnaJ chaperone protein in a radically different manner, namely ATP
      stimulates whereas a nonhydrolyzable ATP analogue inhibits the DnaK-DnaJ complex
      formation. Moreover, the DnaKc94 mutant protein lacking 94 amino acids from its C
      terminal domain, which still possesses at ATPase activity and forms a transient
      complex with protein substrates, does not interact with DnaJ protein. We conclude
      that the DnaK-ADP form, derived from ATP hydrolysis, possesses low affinity to
      the protein substrates but can efficiently interact with DnaJ molecular
      chaperone.

PMID- 7642606
TI  - ATP hydrolysis is required for the DnaJ-dependent activation of DnaK chaperone
      for binding to both native and denatured protein substrates.
AB  - Using two independent experimental approaches to monitor protein-protein
      interactions (enzyme-linked immunosorbent assay and size exclusion high
      performance liquid chromatography) we describe a general mechanism by which DnaJ
      modulates the binding of the DnaK chaperone to various native protein substrates,
      e.g. lambda P, lambda O, delta 32, P1, RepA, as well as permanently denatured
      alpha-carboxymethylated lactalbumin. The presence of DnaJ promotes the DnaK for
      efficient DnaK-substrate complex formation. ATP hydrolysis is absolutely required
      for such DnaJ-dependent activation of DnaK for binding to both native and
      denatured protein substrates. Although ADP can stabilize such as an activated
      DnaK-protein complex, it cannot substitute for ATP in the activation reaction. In
      the presence of DnaJ and ATP, DnaK possesses the affinity to different substrates
      which correlates well with the affinity of DnaJ alone for these protein
      substrates. Only when the affinity of the DnaJ chaperone for its protein
      substrate is relatively high (e.g. delta 32, RepA) can a tertiary complex DnaK
      substrate-DnaJ be detected. In the case that DnaJ binds weakly to its substrate
      (lambda P, alpha-carboxymethylated lactalbumin), DnaJ is only transiently
      associated with the DnaK-substrate complex, but the DnaK activation reaction
      still occurs, albeit less efficiently.

PMID- 7642607
TI  - Molecular cloning of mouse tissue inhibitor of metalloproteinases-3 and its
      promoter. Specific lack of expression in neoplastic JB6 cells may reflect altered
      gene methylation.
AB  - Mouse tissue inhibitor of metalloproteinases-3 (mTIMP-3), a gene specifically not
      expressed in neoplastic JB6 cells, have been isolated recently through the use of
      the mRNA differential display technique (Sun, Y., Hegamyer, G., and Colburn, N.
      H. (1994) Cancer Res. 54, 1139-1144). We report here the full-length mTIMP-3 cDNA
      sequence, the promoter sequence and partial characterization, expression and
      induction of TIMP-3, and the possible molecular basis for the lack of mTIMP-3
      expression in neoplastic JB6 cells. There are three transcripts arising from
      alternative polyadenylation of mouse TIMP-3 gene, having sizes of 4.6, 2.8, and
      2.3 kilobase pairs, respectively. All three TIMP-3 transcripts are expressed in
      preneoplastic but not neoplastic JB6 cells. Computer analysis of cloned TIMP-3
      promoter revealed six AP-1 binding sites, two NF-KB sites, a c-Myc site, and two
      copies of a p53 binding motif separated by eight base pairs with two mismatches
      at the second motif, along with many other cis elements. TIMP-3 gene expression
      was inducible by AP-1 and NF-KB activators, 12-O-tetradecanoylphorbol-13-acetate,
      and tumor necrosis factor-alpha only in preneoplastic cells with an induction
      peak at 2 h post-treatment, suggesting classification of mTIMP-3 as a member of
      the immediate early gene family. Southern blot, mutational analysis, and
      transient transcriptional activation experiments revealed that the lack of
      expression of mTIMP-3 in neoplastic JB6 cells was due neither to gross deletion
      nor to promoter mutation of the gene, nor was there a lack of transcription
      factors required for transcriptional activation. Instead, the lack of TIMP-3
      expression in neoplastic JB6 cells may reflect an abnormal methylation of the
      gene. Both hyper- and hypomethylation of the mTIMP-3 gene are associated with
      complete down-regulation of gene expression in neoplastic JB6 cell lines.
      Treatment of neoplastic cells with the methylase inhibitor 5-azacytidine caused
      reexpression of the mTIMP-3 gene in a tumor cell line that showed
      hypermethylation but not in another that showed hypomethylation of the gene,
      suggesting a complex role for methylation in the silencing of gene expression.

PMID- 7642608
TI  - Characterization of a Ca2+/calmodulin-dependent protein kinase cascade. Molecular
      cloning and expression of calcium/calmodulin-dependent protein kinase kinase.
AB  - Recent studies have demonstrated that Ca2+/calmodulin-dependent protein kinase IV
      (CaM-kinase IV) can mediate Ca(2+)-dependent regulation of gene expression
      through the phosphorylation of transcriptional activating proteins. We have
      previously identified and purified a 68-kDa rat brain CaM-kinase kinase that
      phosphorylates and increases total and Ca(2+)-independent activities of CaM
      kinase IV (Tokumitsu, H., Brickey, D. A., Gold, J., Hidaka, H., Sikela, J., and
      Soderling, T. R. (1994) J. Biol. Chem. 269, 28640-28647). Using a partial amino
      acid sequence of the purified brain kinase, a CaM-kinase kinase cDNA was cloned
      from a rat brain cDNA library. Northern blot analysis showed that CaM-kinase
      kinase mRNA (3.4 kilobases) was expressed in rat brain, thymus, and spleen.
      Sequence analyses revealed that the cDNA encoded a 505-amino acid protein, which
      contained consensus protein kinase motifs and was 30-40% homologous with members
      of the CaM-kinase family. Expression of the cDNA in COS-7 cells yielded an
      apparent 68-kDa CaM-binding protein, which catalyzed in vitro activation in the
      presence of Mg2+/ATP and Ca2+/ CaM of CaM-kinases I and IV but not of CaM-kinase
      II. Co-expression of CaM-kinase kinase with CaM-kinase IV gave a 14-fold
      enhancement of cAMP-response element-binding protein-dependent gene expression
      compared with CaM-kinase IV alone. These results are consistent with the
      hypothesis that CaM-kinases I and IV are regulated through a unique signal
      transduction cascade involving CaM-kinase kinase.

PMID- 7642609
TI  - Anti-cooperative biphasic equilibrium binding of transcription factor upstream
      stimulatory factor to its cognate DNA monitored by protein fluorescence changes.
AB  - Upstream stimulatory factor USF is a human transcriptional activation factor,
      which uses a basic/helix-loop-helix/ leucin zipper (b/HLH/Z) motif to
      homodimerize and recognize specific sequences in the promoter region of both
      nuclear and viral genes transcribed by RNA polymerase II. Steady state
      fluorescence spectroscopy demonstrated that the basic/helix-loop-helix/leucin
      zipper domain of USF binds its DNA targets with high affinity and specificity,
      whereas removal of the leucine zipper yielding the basic/helix-loop-helix minimal
      DNA binding region reduces both affinity and specificity. Stopped flow method
      provided kinetic evidence for a two-step binding process involving rapid
      formation of a protein-DNA intermediate followed by a slow isomerization step,
      which is consistent with the basic region undergoing a random coil to alpha-helix
      folding transition on specific DNA recognition. The leucine zipper is also
      necessary for USF to function as a bivalent homotetramer, capable of binding two
      distinct recognition sites simultaneously and mediating DNA looping under
      physiologic conditions. Titration studies revealed that the first binding event
      has a equilibrium constant Keq = (2.2 +/- 2.0) x 10(9) M-1 for major late
      promoter DNA, whereas the second binding event occurs with a remarkable reduced
      affinity, Keq = (1.2 +/- 0.8) x 10(8) M-1. This anticooperative feature of DNA
      binding by the homotetramer suggests that USF stimulates transcription by
      mediating DNA looping between nearby recognition sites located in class II
      nuclear and viral gene promoters.

PMID- 7642610
TI  - Fatty acid substrate specificities of human prostaglandin-endoperoxide H synthase
      1 and -2. Formation of 12-hydroxy-(9Z, 13E/Z, 15Z)- octadecatrienoic acids from
      alpha-linolenic acid.
AB  - Human prostaglandin-endoperoxide H synthase-1 and -2 (hPGHS-1 and hPGHS-2) were
      expressed by transient transfection of COS-1 cells. Microsomes prepared from the
      transfected cells were used to measure the rates of oxygenation of several 18-
      and 20-carbon polyunsaturated fatty acid substrates including eicosapentaenoic,
      arachidonic, dihomo-gamma-linolenic > alpha-linolenic (delta 9, 12, 15), gamma
      linolenic, and linoleic acids. Comparisons of kcat/Km values indicate that the
      order of efficiency of oxygenation is arachidonate > dihomo-gamma-linolenate >
      linoleate > alpha-linolenate for both isozymes; while the order of efficiency was
      the same for hPGHS-1 and hPGHS-2, alpha-linolenate was a particularly poor
      substrate for hPGHS-1. Gamma-Linolenate and eicosapentaenoate were poor
      substrates for both isozymes, but in each case, these two fatty acids were better
      substrates for hPGHS-2 than hPGHS-1. These studies of substrate specificities are
      consistent with previous studies of the interactions of PGHS isozymes with
      nonsteroidal anti-inflammatory drugs that have indicated that the cyclooxygenase
      active site of PGHS-2 is somewhat larger and more accommodating than that of PGHS
      1. The major products formed from linoleate and alpha-linolenate were
      characterized. 13-Hydroxy-(9Z,11E)-octadecadienoic acid was found to be the main
      product formed from alpha-linoleate by both isozymes. The major products of
      oxygenation of alpha-linolenate were determined by mass spectrometry to be 12
      hydroxy-(9Z,13E/Z,15Z)-octadecatrienoic acids. This result suggests that alpha
      linolenate is positioned in the cyclooxygenase active site with a kink in the
      carbon chain such that hydrogen abstraction occurs from the omega 5-position in
      contrast to abstraction of the omega 8-hydrogen from other substrates.

PMID- 7642611
TI  - Characterization of physical interactions of the putative transcriptional
      adaptor, ADA2, with acidic activation domains and TATA-binding protein.
AB  - RNA polymerase II transcription requires functional interactions between
      activator proteins bound to upstream DNA sites and general factors bound to the
      core promoter. Accessory transcription factors, such as adaptors and
      coactivators, have important, but still unclear, roles in the activation process.
      We tested physical interactions of the putative adaptor ADA2 with activation
      domains derived from acidic activator proteins and with certain general
      transcription factors. ADA2 associated with the herpesvirus VP16 and yeast GCN4
      activation domains but not with the activation domain of yeast HAP4, which
      previously was shown to be independent of ADA2 function in vivo and in vitro.
      Furthermore, the amino terminus of ADA2 directly interacted with the VP16
      activation domain, suggesting that ADA2 provides determinants for interaction
      between activation domains and the adaptor complex. Both TATA-binding protein
      (TBP) and TFIIB have previously been shown to interact directly with the VP16
      activation domain in vitro (Stringer, K. F., Ingles, C. J., and Greenblatt, J.
      (1990) Nature 345, 783-786; Lin, Y. S., Ha, I., Maldonado, E., Reinberg, D., and
      Green, M. R. (1991) Nature 353, 569-571). Interestingly, when binding was tested
      between VP16 and these general factors in yeast nuclear extracts, both factors
      interacted with VP16, but only the TBP/VP16 association was dependent on ADA2. In
      addition, ADA2 physically associated with TBP, but not with TFIIB. These results
      suggest that the role of ADA2 in transcriptional activation is to promote
      physical interaction between activation domains and TBP.

PMID- 7642612
TI  - Expression of a functionally active human renal sodium-calcium exchanger lacking
      a signal sequence.
AB  - The Na+-Ca2+ exchanger is an unusual membrane transport protein as it contains an
      NH2-terminal signal sequence which is co-translationally removed in the
      endoplasmic reticulum during synthesis. To determine if the signal sequence was
      essential for biosynthesis, mutations were introduced in the NH2 terminus of the
      cDNA coding for the human renal Na+-Ca2+ exchanger in order to alter processing
      of the protein. To prevent cleavage of the signal sequence during biosynthesis,
      the last residue of the consensus signal sequence, Ala-1, was changed to Phe.
      Deletion mutants were also constructed to encode for exchangers which lacked the
      signal sequence, the signal sequence and the first extracellular loop, or all of
      the NH2 terminus including the first transmembrane segment of the mature protein.
      These mutants were expressed in HEK 293 cells and assayed for Na+-Ca2+ exchange
      activity. Mutants lacking either a signal sequence or containing a noncleavable
      signal sequence were still targeted to the plasma membrane, where they exhibited
      Na+-Ca2+ exchange activity. By contrast, the mutants which had more than the
      signal sequence deleted did not demonstrate any exchange activity. These mutants
      were, however, still integrated into the membrane and were resistant to alkali
      extraction. These results show that the signal sequence is not essential for
      biogenesis of the Na+-Ca2+ exchanger and suggests that the molecule contains one
      or more internal signal sequences for insertion into the membrane during
      biosynthesis.

PMID- 7642613
TI  - Demonstration of a glycogen/glucose 1-phosphate cycle in hepatocytes from fasted
      rats. Selective inactivation of phosphorylase by 2-deoxy-2-fluoro-alpha-D
      glucopyranosyl fluoride.
AB  - In search for a nonmetabolized, superior glucose analogue to study the mechanism
      of glucose-induced glycogen synthesis, we have tested 2-deoxy-2-fluoro-alpha-D
      glucopyranosyl fluoride, which inhibits muscle phosphorylase beta 10-fold better
      than dose glucose (Street, I.P., Armstrong, C.R., and Withers, S.G. (1986)
      Biochemistry 25, 6021-6027). In a gel-filtered liver extract, 0.6 mM analogue and
      10 mM glucose equally accelerated the inactivation of phosphorylase and shortened
      the latency before the activation of glycogen synthase. The analogue was not
      measurably defluorinated or phosphorylated by intact hepatocytes, as monitored by
      19F NMR. When added to isolated hepatocytes, 10 mM analogue inactivated
      phosphorylase more extensively than did 50 mM glucose, but unlike glucose, it did
      not result in the activation of glycogen synthase. Therefore, the binding of
      glucose to phosphorylase alpha can account for the inactivation of phosphorylase,
      but the metabolism of glucose (probably to Glc-6-P) appears to be required to
      achieve activation of glycogen synthase. The livers of overnight-fasted,
      anesthetized mice contained appreciable amounts of both phosphorylase alpha and
      glycogen synthase alpha, without net glycogen accumulation. Likewise, hepatocytes
      isolated from fasted rats and incubated with 10 mM glucose contained 41% of
      phosphorylase and 32% of glycogen synthase in the alpha form, and these values
      remained stable for 1 h, while glycogen accumulated at only 22% of the rate
      expected from the glycogen synthase activity. The addition of 10 mM analogue
      decreased phosphorylase alpha to 10% without significant change in glycogen
      synthase alpha (38%), but with a 4-fold increased rate of glycogen accumulation.
      These findings imply that synthase alpha is fully active in the liver of the
      fasted animal and that the absence of net glycogen synthesis is due to continuous
      glycogenolysis by phosphorylase alpha.

PMID- 7642614
TI  - Properties and developmental regulation of polysialyltransferase activity in the
      chicken embryo brain.
AB  - The properties and developmental regulation of vertebrate polysialyltransferase
      (PST), an enzyme activity responsible for extension of alpha 2,8-linked sialic
      acid homopolymers (PSA) associated with the fifth Ig domain of the neural cell
      adhesion molecule (NCAM). have been studied. The assay for PST used exogenous
      NCAM as a substrate, with a PSA-specific endoneuraminidase as a control for
      specificity. Optimal conditions for PST activity at 37 degrees C were found to be
      pH 6.0 in the presence of divalent cations (Mn2+, 20mM). The enzyme Km was found
      to increase with increasing polymer length, ranging from 0.7 to 0.07 microns. The
      developmental regulation both of PST activity and of the addition of PSA to NCAM
      were studied in chick whole brain, tectum, and cerebellum and found to be
      precisely coordinated. In each tissue PSA and PST were highest during early
      stages of morphogenesis, followed by a decrease as development reached
      completion. The insertion of the VASE exon in the fourth Ig domain of NCAM was
      also found to parallel closely the developmental down-regulation of PSA, and on
      this basis could be considered a potential determinant in the specific
      polysialylation of NCAM. However in direct tests of this hypothesis in
      transfected cells the presence of VASE did not markedly alter the level of NCAM
      polysialylation or alter the affinity of PST for the NCAM substrate.

PMID- 7642615
TI  - HIV-1 envelope glycoproteins induce activation of activated protein-1 in CD4+ T
      cells.
AB  - Activation of CD4 positive T cells is a primary requirement for human
      immunodeficiency virus (HIV) entry, efficient HIV replication, and progression to
      AIDS, Utilizing CD4 positive T cell lines and purified T cells from normal
      individuals, we have demonstrated that native envelope glycoproteins of HIV, gp
      160, can induce activation of transcription factor, activated protein-1 (AP-1).
      The stimulatory effects of gp160 are mediated through the CD4 molecule, since
      treatment of gp160 with soluble CD4-IgG abrogates its activity, and CD4 negative
      T cell lines fail to be stimulated with gp160. Immunoprecipitation of the gp 160
      induced nuclear extracts with polyclonal antibodies to Fos and Jun proteins
      indicates that AP-1 complex is comprised of members of these family of proteins.
      The gp160-induced AP-1 complex is dependent upon protein tyrosine phosphorylation
      and is protein synthesis-independent. This stimulation can also be abolished by
      inhibitors of protein kinase C, but it is unaffected by calcium channel blocker
      or cyclosporine A. This gp160 treatment adversely affects the functional
      capabilities of T cells: pre-treatment of CD4+ T cells with gp160 for 4 h at 37
      degrees C inhibited anti-CD3-induced interleukin-2 secretion. Effects similar to
      gp160 were seen with anti-CD4 mAb. The aberrant activation of AP-1 by gp160 in
      CD4 positive T cells could result in up-regulation of cytokines containing AP-1
      sites, e.g. interleukin-3 and granulocyte macrophage colony-stimulating factor,
      and concurrently lead to T cell unresponsiveness by inhibiting interleukin-2
      secretion.

PMID- 7642616
TI  - Selection of a suppressor mutation that restores affinity of an oligonucleotide
      inhibitor for thrombin using in vitro genetics.
AB  - The thrombin aptamer is a single-stranded DNA of 15 nucleotides that was
      identified by the selection of thrombin-binding molecules from a large
      combinatorial library of oligonucleotides. This prototype aptamer of thrombin has
      a unique double G-tetrad structure capable of inhibiting thrombin at nanomolar
      concentrations through binding to a specific region within thrombin exosite I.
      Substitution of arginine 70 in thrombin exosite I with glutamic acid effectively
      eliminated binding of the prototype thrombin aptamer. In contrast, aptamers
      selected against R70E thrombin were able to bind and inhibit both wild-type and
      R70E thrombins, and displayed potassium-independent inhibition. Aptamers selected
      against R70-E thrombin bound to sites identical or overlapping with that of the
      prototype thrombin aptamer. These aptamers retained the potential to form double
      G-tetrad structures; however, these structures would be destabilized by a T-->A
      substitution, disrupting the T4-T13 base pairing found in the prototype. This
      destabilization appeared to be partially compensated by newly recruited
      structural elements. Thus, selection against R70E thrombin did not lead to
      aptamers that bound to alternative sites, but instead to ssDNA structures with a
      suppressor mutation that accommodated the mutation in thrombin within a double G
      tetrad context. These results provide insight into the aptamer-thrombin
      interaction and suggest that the binding site for the prototype is the dominant
      aptamorigenic site on thrombin.

PMID- 7642617
TI  - An alleged yeast polyphosphate kinase is actually diadenosine-5', 5"'-P1,P4
      tetraphosphate alpha,beta-phosphorylase.
AB  - Polyphosphates are a major constituent of the yeast Saccharomyces cerevisiae. A
      purification of the enzyme polyphosphate kinase (E.C. 2.7.4.1) from this organism
      has been reported (Felter, S., and Stahl, A.J.C. (1973) Biochimie (Paris) 55, 245
      251). The assay for activity used in this purification was the production of 32P
      labeled nucleotide, presumed to be ATP, in the presence of [32P]polyphosphate and
      ADP. We have found that this assay does not reflect the activity of a
      polyphosphate kinase but rather the combination of an exopolyphosphatase,
      releasing free [32P]phosphate from the added [32P]polyphosphate, and the ADP
      [32P]phosphate exchange activity of the enzyme diadenosine 5',5"'-P1, P4
      tetraphosphate alpha, beta-phosphorylase (Ap4A phosphorylase). We also present
      direct evidence for the formation of an enzyme-AMP intermediate in the actin of
      Ap4A phosphorylase.

PMID- 7642618
TI  - P-glycoprotein is stably inhibited by vanadate-induced trapping of nucleotide at
      a single catalytic site.
AB  - P-glycoprotein (Pgp or multidrug-resistance protein) shows drug-stimulated ATPase
      activity. The catalytic sites are known to be of low affinity and specificity for
      nucleotides. From the sequence, two nucleotide sites are predicted per Pgp
      molecule. Using plasma membranes from a multidrug-resistant Chinese hamster ovary
      cell line, which are highly enriched in Pgp, we show that vanadate-induced
      trapping of nucleotide at a single catalytic site produces stably inhibited Pgp,
      with t 1/2 for reactivation of ATPase activity of 84 min at 37 degrees C and >30
      h at 4 degrees C. Reactivation of ATPase correlated with release of trapped
      nucleotide. Concentrations of MgATP and MgADP required to produce 50% inhibition
      were 9 and 15 microM, respectively, thus the apparent affinity for nucleotide is
      greatly increased by vanadate-trapping. The trapped nucleotide species was ADP.
      Divalent Cation was required, with magnesium, manganese, and cobalt all
      effective: cobalt yielded a very stable inhibited species, t1/2 at 37 degrees C =
      18 h. No photocleavage of Pgp was observed after vanadate trapping with MgATP,
      nor was UV-induced photolabeling of Pgp by trapped adenine nucleotide observed.
      Vanadate-trapping with 8-azido-ATP followed by UV irradiation caused permanent
      inactivation and specific labeling of Pgp. Vanadate-induced inhibition was also
      shown with pure, reconstituted Pgp, with similar characteristics to those in
      plasma membranes. Vanadate trapping overcomes technical difficulties posed by
      lack of high affinity nucleotide-binding site(s) or a covalent enzyme-phosphate
      catalytic intermediate in Pgp. The finding that vanadate trapping of nucleotide
      at just one site/Pgp is sufficient to give full inhibition at ATPase activity
      shows that the two predicted nucleotide sites can not function independently as
      catalytic sites.

PMID- 7642619
TI  - Cleavage specificity of porcine follipsin.
AB  - Follipsin purified from the follicular fluid of porcine ovaries was studied for
      its specificity against various synthetic and peptide substrates. The enzyme
      cleaved only by an endopeptidase activity at the amide and peptide bonds of Arg
      X, indicating strict specificity of the S1 pocket for arginine. The specificity
      for pocket S2 appears to favor either hydrophobic or basic side chains. A 10
      residue peptide containing a portion of the activation site of human tissue
      plasminogen activator was synthesized and tested with the enzyme. The peptide was
      cleaved by follipsin at the Arg-Ile bond, as expected from the specificity
      deduced above. Furthermore, the enzyme successfully converted single-chain
      precursor tissue plasminogen activator (sctPA) to its active, two-chain form by
      cleaving the corresponding peptide bond. Comparison of the rates of single-chain
      precursor tissue plasminogen activator activation and tissue plasminogen
      activator peptide hydrolysis revealed that the former is a more efficient
      substrate than the latter.

PMID- 7642620
TI  - Activation of rat choline acetyltransferase by limited proteolysis.
AB  - In the past, purification of choline acetyltransferase (ChAT, EC 2.3.1.6.), the
      enzyme responsible for the biosynthesis of the neurotransmitter acetylcholine,
      has yielded fragmented species of the enzyme. The nature and possible function of
      these forms of ChAT are not well understood. Using a bacterial expression system,
      recombinant rat ChAT in its active form has been purified to homogeneity. The
      purified enzyme was found to be activated to >25-fold when assayed at low ionic
      strength and >5-fold when assayed at high ionic strength by limited proteolysis
      with either trypsin or chymotrypsin, but not with proteinase K. The activated
      ChAT shows an increased Km for both substrates, diminished sensitivity to salt
      activation and a pH optimum that is shifted approximately 1 pH unit. On a
      denaturing SDS-polyacrylamide gel, the activated ChAT is composed of three to
      four polypeptides; however, it migrates as an intact 68-k-Da protein species on
      gel filtration. In order to delineate the site of cleavage by proteolysis, the
      newly generated fragments have been subjected to N-terminal sequencing. By
      comparing cleavage sites between trypsin and chymotrypsin, the putative
      activation sites were identified.

PMID- 7642621
TI  - Tumor necrosis factor-alpha inhibits surfactant protein C gene transcription.
AB  - Pulmonary surfactant protein C (SP-C) is a 3.7-kDa, hydrophobic peptide secreted
      by alveolar type II epithelial cells. SP-C enhances surface tension lowering
      activity of surfactant phospholipids that is critical to the maintenance of
      alveolar volume at end expiration. The proinflammatory cytokine, tumor necrosis
      factor alpha (TNF-alpha), decreased SP-C mRNA within 24 h of intratracheal
      administration to mice. In vitro, TNF-alpha decreased SP-C mRNA in a time-and
      dose-dependent manner, reducing the steady state levels of SP-C mRNA by 3-5 fold.
      In contrast, TNF-alpha induced intercellular adhesion molecule-1 expression in
      both mouse lung and murine lung epithelial cell lines. Nuclear run-on analysis
      demonstrated that transcription of both the endogenous SP-C gene and a human SP-C
      promoter-driven transgene was inhibited by TNF-alpha. TNF-alpha decreased mouse
      SP-C chloramphenicol acetyltransferase mRNA in stably transfected murine
      epithelial cells. Deletion analysis of the SP-C promoter region demonstrated that
      TNF-alpha inhibited gene expression in constructs containing 320 base pairs 5'
      from the start of transcription of the mouse SP-C gene. Inhibition of surfactant
      protein C gene transcription by TNF-alpha may contribute to the abnormalities of
      surfactant homeostasis associated with pulmonary injury and infection.

PMID- 7642622
TI  - Alcohols inhibit a cloned potassium channel at a discrete saturable site.
      Insights into the molecular basis of general anesthesia.
AB  - The molecular basis of general anesthetic action on membrane proteins that
      control ion transport is not yet understood. In a previous report (Covarrubias,
      M., and Rubin, E. (1993) Proc. Natl. Acad. Sci. 90, 6957-6960), we found that low
      concentrations of ethanol (17-170mM) selectively inhibited a noninactivating
      cloned K+ channel encoded by Drosophila Shaw2. Here, we have conducted
      equilibrium dos-inhibition experiments, single channel recording, and mutagenesis
      in vitro to study the mechanism underlying the inhibition of Shaw2K+ channels by
      a homologous series of n-alkanols (ethanol to 1-hexanol). The results showed
      that: (i) these alcohols inhibited Shaw2 whole-cell currents, the equilibrium
      dose-inhibition relations were hyperbolic, and competition experiments revealed
      the presence of a discrete site of action, possibly a hydrophobic pocket; (ii)
      this pocket may be part of the protein because n-alkanol sensitivity can be
      transferred to novel hybrid K+ channels composed of Shaw2 subunits and homologous
      ethanol-insensitive subunits: (iii) moreover, a hydrophobic point mutation within
      a cytoplasmic loop of an ethanol-insensitive K+ channel (human Kv3.4) was
      sufficient to allow significant inhibition by n-alkanols, with a dose-inhibition
      relation that closely resembled that of wildtype Shaw2 channels; and (iv) 1
      butanol selectively inhibited long duration single channel openings in a manner
      consistent with a direct effect on channel gating. These results strongly suggest
      that a discrete site within the ion channel protein is the primary locus of
      alcohol and general anesthetic action.

PMID- 7642623
TI  - Glycoprotein 330/low density lipoprotein receptor-related protein-2 mediates
      endocytosis of low density lipoproteins via interaction with apolipoprotein B100.
AB  - The ability of glycoprotein 330/low density lipoprotein receptor-related protein
      2 (LRP-2) to function as a lipoprotein receptor was investigated using cultured
      mouse F9 teratocarcinoma cells. Treatment with retinoic acid and dibutyryl cyclic
      AMP, which induces F9 cells to differentiate into endoderm-like cells, produced a
      50-fold increase in the expression of LRP-2. Levels of the other members of the
      low density lipoprotein (LDL) receptor (LDLR) family, including LDLR, the very
      low density lipoprotein receptor, and LRP-1, were reduced. When LDL catabolism
      was examined in these cells, it was found that the treated cells endocytosed and
      degraded at 10-fold higher levels than untreated cells. The increased LDL uptake
      coincided with increased LRP-2 activity of the treated cells, as measured by
      uptake of both 125I-labeled monoclonal LRP-2 antibody and the LRP-2 ligand
      prourokinase. The ability of LDL to bind to LRP-2 was demonstrated by solid-phase
      binding assays. This binding was inhibitable by LRP-2 antibodies, receptor
      associated protein (the antagonist of ligand binding for all members of the LDLR
      family), or antibodies to apoB100, the major apolipoprotein component of LDL. In
      cell assays, LRP-2 antibodies blocked the elevated 125I-LDL internalization and
      degradation observed in the retinoic acid/dibutyryl cyclic AMP-treated F9 cells.
      A low level of LDL endocytosis existed that was likely mediated by LDLR since it
      could not be inhibited by LRP-2 antibodies, but was inhibited by excess LDL,
      receptor-associated protein, or apoB100 antibody. The results indicate that LRP-2
      can function to mediate cellular endocytosis of LDL, leading to its degradation.
      LRP-2 represents the second member of the LDLR family identified as functioning
      in the catabolism of LDL.

PMID- 7642624
TI  - Purification and characterization of novel plasma membrane phosphatidate
      phosphohydrolase from rat liver.
AB  - An N-ethylmaleimide-insensitive phosphatidate phosphohydrolase, which also
      hydrolyzes lysophosphatidate, was isolated from the plasma membranes of rat
      liver. The specific activity of an anionic form of the enzyme (53 kDa, pI < 4)
      was increased 2700-fold. A cationic form of enzyme (51 kDa, pI = 9) was purified
      to homogeneity, but the -fold purification was low because the activity of the
      highly purified enzyme was unstable. Immunoprecipitating antibodies raised
      against the homogeneous protein confirmed the identity of the cationic protein as
      the phosphohydrolase and were used to identify the anionic enzyme. Both forms are
      integral membrane glycoproteins that were converted to 28-kDa proteins upon
      treatment with N-glycanase F. Treatment of the anionic form with neuraminidase
      allowed it to be purified in the same manner as the cationic enzyme and yielded
      an immunoreactive protein with a molecular mass identical to the cationic
      protein. Thus, the two ionic forms most likely represent different sialated
      states of protein. An immunoreactive 51-53-kDa protein was detected in rat liver,
      heart, kidney, skeletal muscle, testis, and brain. Little immunoreactive 51-53
      kDa protein was detected in rat thymus, spleen, adipose, or lung tissue. This
      work provides the tools for determining the regulation and function of the
      phosphatidate phosphohydrolase in signal transduction and cell activation.

PMID- 7642625
TI  - Horseradish peroxidase His-42 --> Ala, His-42 --> Val, and Phe-41 --> Ala
      mutants. Histidine catalysis and control of substrate access to the heme iron.
AB  - Polyhistidine-tagged horseradish peroxidase (hHRP) and its F41A, H42A, and H42V
      mutants have expressed in an insect cell system. Kinetic studies show that the
      rates of Compound I formation and peroxidative catalysis are greatly decreased by
      the His-42 mutation. Furthermore, Compound II is not detected during turnover of
      the His-42 mutants. Compounds I and II are the two- and one-electron oxidized
      intermediates, respectively, of hHRP. In peroxygenative catalysis, the F41A and
      H42A mutants catalyze thioanisole sufoxidation 100 and 10 times faster,
      respectively, than hHRP. Styrene epoxidation is catalyzed by both the Phe-41 and
      His-42 mutants but not by wild-type hHRP. The higher peroxygenase activity of the
      mutants reflects increased accessibility of the ferryl species. This is indicated
      by the finding that, contrary to the reaction with wild-type hHRP, reaction of
      phenyldiazene with the F41A mutant yields a new and unidentified product, and the
      same reaction with the His-42 mutants yields phenyl-iron complexes. Phe-41 and
      His-42 thus shield the iron-centered catalytic species, and His-42 plays a key
      catalytic role in the formation of Compound I. The peroxygenase activities of the
      Phe-41 and His-42 mutants approach those of cytochrome P450.

PMID- 7642626
TI  - Conformations of peptides corresponding to fatty acylation sites in proteins. A
      circular dichroism study.
AB  - Fatty acid acylation is a posttranslational modification found in membrane
      proteins that have hydrophobic sequences serving as transmembrane segments as
      well as those that do not have them. The fatty acids myristate and palmitate are
      linked through an amide bond to N-terminal glycine and SH of cysteine via a
      thioester bond, respectively. In order to elucidate whether or how fatty acid
      acylation would modulate peptide structure, especially in hydrophobic
      environment, we have carried out circular dichroism studies on synthetic peptides
      both hydrophobic and hydrophilic in nature, corresponding to fatty acylation
      sites and their fatty acyl derivatives. The hydrophilic peptides were
      approximately 12 residues in length as studies on proteins modified by site
      directed mutagenesis indicated that a peptide segment of approximately 12
      residues is sufficient to direct acylation as well as membrane association,
      especially when the fatty acid is myristic acid. The peptide corresponding to a
      transmembrane segment composed of 31 residues as well as its palmitoyl derivative
      was found to adopt alpha-helical structure. Acylation appeared to favor increased
      partitioning into miscelles even in the case of a hydrophobic peptide. The
      hydrophilic peptides and their myristoyl or palmitoyl derivatives showed very
      little ordered structure in micelles. Our results suggest that the myristoyl and
      the palmitoyl moieties do not have the ability to "force" a hydrophilic peptide
      segment into a hydrophobic micellar environment. Thus, the mere presence of a
      fatty acid moiety may not be sufficient for membrane binding and recycling as is
      assumed especially in proteins in which no hydrophobic segment is present.

PMID- 7642627
TI  - Formation of 2-hydroxydeoxyadenosine triphosphate, an oxidatively damaged
      nucleotide, and its incorporation by DNA polymerases. Steady-state kinetics of
      the incorporation.
AB  - We found that hydroxylation occurs at the C-2 position of adenine by oxygen
      radical treatment (Fe2+-EDTA) of dA, dATP, and single- and double-stranded DNA.
      This oxidatively damaged base, 2-hydroxyadenine, was produced 3-6-fold and 40
      fold less than 8-hydroxyguanine when monomers and polynucleotides, respectively,
      were treated. To determine whether the damaged nucleotide, 2
      hydroxydeoxyadenosine triphosphate (2-OH-dATP), is incorporated into a growing
      DNA, and to reveal the kinds of nucleotides opposite which 2-OH-dATP is
      incorporated, calf thymus DNA polymerase alpha and the Klenow fragment of
      Escherichia coli DNA polymerase I were used in vitro DAN synthesis in the
      presence of 2-OH-dATP. DNA polymerase alpha incorporated the nucleotide opposite
      T and C in the DNA template. On the other hand, in an experiment using the Klenow
      fragment, incorporation of 2-OH-dATP was observed only opposite T. Steady-state
      kinetic studies indicated that incorporation of 2-OH-dATP by DNA polymerase alpha
      opposite T was favored over that opposite C by a factor of only 4.5. These
      results indicate that 2-OH-dATP, an oxidatively damaged nucleotide, is a
      substrate for DNA polymerases and is incorporated incorrectly by the replicative
      DNA polymerase.

PMID- 7642628
TI  - Markedly decreased expression of glutathione S-transferase pi gene in human
      cancer cell lines resistant to buthionine sulfoximine, an inhibitor of cellular
      glutathione synthesis.
AB  - Buthionine sulfoximine (BSO) is a synthetic amino acid that irreversibly inhibits
      an enzyme, gamma-glutamylcysteine synthetase (gamma-GCS), which is a critical
      step in glutathione biosynthesis. We isolated three BSO-resistant sublines,
      KB/BSO1, KB/BSO2, and KB/BSO3, from human epidermoid cancer KB cells. These cell
      lines showed 10-to 13-fold higher resistance to BSO, respectively, and had
      collateral sensitivity to cisplatin, ethacrynic acid, and alkylating agents such
      as melphalan and nitrosourea. Cellular levels of glutathione S-transferase pi
      (GST-pi) and its mRNA in BSO-resistant cell lines were less than 10% of the
      parental cells. Nuclear run-on assay showed that the transcriptional activity of
      GST-pi was decreased in BSO-resistant cells, and transient transfection of GST-pi
      promoter-chloramphenicol acetyltransferase constructs revealed that the sequences
      between -130 and -80 base pairs of the 5'-flanking region wer at least partially
      responsible for the decreased expression of the GST-pi gene. By contrast, gamma
      GCS mRNA levels were 3-to 5-fold higher in resistant cell lines than in KB cells,
      and the gamma-GCS gene was found to be amplified in the BSO-resistant cells
      lines. GST-pi mRNA levels appeared to be inversely correlated with gamma-GCS mRNA
      levels in BSO-resistant cells. We further established the transfectants, KB/BSO3
      pi1 and KB/ BSO2-pi2, that overexpressed GST-pi, from KB/BSO3, after introducing
      a GST-pi expression plasmid. These two transfectants had similar levels in gamma
      GCS mRNA, drug sensitivity to alkylating agents, and glutathione content at those
      of KB cells. These findings suggest that the cellular levels of GST-pi and gamma
      GCS might be co-regulated in these novel BSO-resistant cells.

PMID- 7642629
TI  - The interaction of fibulin-1 with fibrinogen. A potential role in hemostasis and
      thrombosis.
AB  - The fibulins are an emerging family of extracellular matrix and blood proteins
      presently having two members designated fibulin-1 and -2. Fibulin-1 is the
      predominant fibulin in blood, present at a concentration of 30-40 micrograms/ml
      (approximately 1000-fold higher than fibulin-2). During the course of isolating
      fibulin-1 from plasma by immunoaffinity chromatography, a 340-kDa polypeptide was
      consistently found to co-purify. This protein was identified as fibrinogen (Fg)
      based on its electrophoretic behavior and reactivity with Fg monoclonal
      antibodies. Radioiodinated fibulin-1 was shown to bind to Fg transferred onto
      nitrocellulose filters after SDS-polyacrylamide gel electrophoresis. In enzyme
      linked immunosorbent assay, fibulin-1 bound to Fg (and fibrin) adsorbed onto
      microtiter well plastic, and conversely, Fg bound to fibulin-1-coated wells. The
      binding of Fg to fibulin-1 was also observed in surface plasmon resonance assays,
      and a dissociation constant (Kd) of 2.9 +/- 1.6 microM was derived. In addition,
      fluorescence anisotropy experiments demonstrated that the interaction was also
      able to occur in fluid phase, which suggests that complexes of fibulin-1 and Fg
      could exist in the blood. To localize the portion of Fg that is responsible for
      interacting with fibulin-1, proteolytic fragments of Fg were evaluated for their
      ability to promote fibulin-1 binding. Fragments containing the carboxyl-terminal
      region of the Bbeta chain (residues 216-468) were able to bind to fibulin-1. In
      addition, it was found that fibulin-1 was able to incorporate into fibrin clots
      formed in vitro and was immunologically detected within newly formed fibrin
      containing thrombi associated with human atherectomy specimens. The interaction
      between fibulin-1 and Fg highlights potential new roles for fibulin-1 in
      hemostasis as well as thrombosis.

PMID- 7642630
TI  - Regulation of phospholipase D by protein kinase C in human neutrophils.
      Conventional isoforms of protein kinase C phosphorylate a phospholipase D-related
      component in the plasma membrane.
AB  - In a variety of intact cells, phorbol esters are known to activate phospholipase
      D. In a cell-free system consisting of plasma membrane and cytosol from human
      neutrophils, phorbol esters activated phospholipase D in an adenosine nucleotide
      triphosphate-dependent manner. ATP gamma S (adenosine 5'-O-(thiotriphosphate))
      was 2-3-fold more effective than ATP, while ADP and AppNHp (adenyl-5'-yl
      imidodiphosphate) were ineffective, and activation was blocked by the kinase
      inhibitor staurosporine. In cytosol deplete of protein kinase C by chromatography
      on threnoine-Sepharose, phorbol ester-dependent activation was lost, but was
      restored upon addition of purified rat brain protein kinase C. The target for
      phosphorylation was shown to be the plasma membrane plasma membrane was
      phosphorylated using ATP gamma S/phorbol 12,13-dibutyrate and protein kinase C
      and was reisolated to remove activators. Upon adding nucleotide-depleted cytosol,
      activator-independent phospholipase D activity was seen. Using this
      prephosphorylation protocol, PKC-dependent activation of plasma membranes was
      found to require micromolar calcium, implicating a conventional protein kinase C.
      Using recombinant isoforms of protein kinase C, only the conventional isoforms
      showed significant activation, with the following rank order of potency: beta 1 >
      alpha > gamma; the beta 2, delta, epsilon, eta, and sigma isoforms showed little
      or no activity. Thus, conventional isoform(s) of protein kinase C activate
      neutrophil phospholipase D by phosphorylating a target protein located in the
      plasma membrane.

PMID- 7642631
TI  - Blocked RecA protein-mediated DNA strand exchange reactions are reversed by the
      RuvA and RuvB proteins.
AB  - RecA protein is unable to complete a DNA strand exchange reaction between a
      circular single-stranded DNA and a linear duplex DNA substrate with heterologous
      sequences of 375 base pairs at the distal end. Instead, it generates a branched
      intermediate in which strand exchange has proceeded up to the homology/heterology
      junction. Addition of the RuvA and RuvB proteins to these stalled intermediates
      leads to the rapid conversion of intermediates back to the original substrates.
      The reversal reaction is initiated at the branch, and the hybrid DNA is unwound
      in the direction opposite to that of the RecA reaction that created it. Under
      optimal conditions the rate of the reaction exhibits only a modest dependence on
      the length of hybrid DNA that must be unwound. Products of the reversal reaction
      are detected within minutes after addition of RuvAB, and appear with an apparent
      first order progress curve, exhibiting a t1/2 in the range of 6-12 min under
      optimal conditions. Few molecules that have undergone only partial reversal are
      detected. This suggests that the assembly or activation of RuvAB on the branched
      substrate is rate-limiting, while any migration of RuvAB on the DNA to effect
      unwinding of the hybrid DNA (and reformation of substrate DNA) is very fast. The
      results are discussed in context of the role of RuvA and RuvB proteins in
      recombinational DNA repair. We suggest that one function of the RuvAB proteins is
      to act as an antirecombinase, to eliminate intragenomic crossovers between
      homologous segments of the bacterial chromosome that might otherwise lead to
      deleterious inversions or deletions.

PMID- 7642632
TI  - Characterization of the interleukin-4 nuclear activated factor/STAT and its
      activation independent of the insulin receptor substrate proteins.
AB  - The activation of a latent DNA binding factor by interleukin-4 (IL-4), the IL-4
      nuclear activated factor (IL-4 NAF), occurs within minutes of IL-4 binding to its
      receptor. Molecular characterization of IL-4NAF by ultraviolet light cross
      linking experiments revealed a single protein of 120-130 kDa in contact with the
      DNA target site. Glycerol gradient sedimentation analysis indicated a molecular
      mass of IL-4 NAF consistent with a monomer that is capable of binding DNA. The IL
      4 NAF target site is a palindromic sequence that is also recognized by the
      interferon-induced transcription factor, p91/STAT1 alpha. However, IL-4 NAF and
      p91/STAT1 alpha display distinguishable DNA binding specificities that may
      generate one level of specificity in the expression of target genes. Previous
      studies suggested the involvement of the insulin receptor substrate-1 (IRS-1) in
      the IL-4 signal transduction pathway. Although IRS-1 is involved in the
      stimulation of mitogenesis, our results demonstrate that activation of IL-4 NAF
      is independent of IRS-signaling proteins. The results of this study indicate that
      IL-4 stimulates bifurcating signal pathways that can direct mitogenesis via the
      IRS-signaling proteins and specific gene expression via the IL-4 NAF.

PMID- 7642633
TI  - A TATA-less promoter containing binding sites for ubiquitous transcription
      factors mediates cell type-specific regulation of the gene for transcription
      enhancer factor-1 (TEF-1).
AB  - TEF-1 is a tissue-specific human transcription factor which binds to and
      activates transcription from the SV40 early promoter and the HPV-16 E6/E7
      promoter and may be involved in regulation of muscle-specific and placenta
      specific gene expression. To investigate the mechanism of its tissue-specific
      expression, we have isolated up to 3 kilobase pairs of 5'-flanking DNA and
      characterized the promoter of the gene for TEF-1. Multiple transcription start
      sites centering on a motif similar to the initiator element (Inr) were
      identified. A minimal promoter, which contains no recognizable TATA element but
      contains an Inr, delimited at -137 base pairs had full transcriptional activity
      both in vivo in HeLa cells and in vitro in HeLa cell extracts. This promoter is
      also highly active in vitro in lymphoid cell extracts, but not in vivo in
      lymphoid cell lines, which do not express the endogenous TEF-1 gene. The minimal
      promoter, which is sufficient to direct tissue-specific expression of the TEF-1
      gene in vivo, contains multiple sites which bind the ubiquitous transcription
      factors Sp1 and ATF-1. Mutation of the Inr completely abolished transcription
      from the major start site while transcription from the minor sites was slightly
      augmented. Inactivation of the proximal Sp1 site abolished transcription from the
      principle start site and increased transcription from a 5' minor start site.
      Insertion of a TATA box element did not qualitatively alter the pattern of start
      site usage which seemed to be dependent upon integrity of the upstream Sp1 site.
      These observations suggest a "cross-talk" between the Inr and a proximal element
      to fix transcription start sites, which is independent of spacing and the
      presence of a TATA element.

PMID- 7642634
TI  - Molecular cloning and functional expression of a novel CC chemokine receptor cDNA
      from a human basophilic cell line.
AB  - We report the cloning and characterization of a novel basophil CC chemokin
      receptor, K5-5, from the human immature basophilic cell line KU-812. The
      predicted protein sequence of K5-5 shows only 49% identity to the macrophage
      inflammatory protein-1 alpha/RANTES receptor (CC CKR-1) and 47% identity to
      monocyte chemotactic protein-1 receptor (b form), suggesting that this cDNA
      encodes a novel member of the CC chemokine receptor family. Analysis of K5-5 mRNA
      expression indicates that it is restricted to leukocyte-rich tissues. In
      addition, we have shown significant levels of K5-5 mRNA in human basophils, which
      were up-regulated by treatment with interleukin-5. The CC chemokines, Macrophage
      inflammatory protein-1 alpha, RANTES, and monocyte chemotactic protein-1 were
      able to stimulate a Ca(2+)-activated chloride channel in Xenopus laevis oocytes
      injected with K5-5 cRNA, whereas no signal was detected in response to monocyte
      chemotactic protein-2, macrophage inflammatory protein-1 beta, or the CXC
      chemokine, interleukin-8. Taken together, these results indicate for the first
      time the presence of a CC chemokine receptor on basophils, which functions as a
      "shared" CC chemokine receptor and may therefore be implicated in the
      pathogenesis of basophil-mediated allergic diseases.

PMID- 7642635
TI  - Studies on the catalytic mechanism of five DNA glycosylases. Probing for enzyme
      DNA imino intermediates.
AB  - DNA glycosylases catalyze scission of the N-glycosylic bond linking a damaged
      base to the DNA sugar phosphate backbone. Some of these enzymes carry out a
      concomitant abasic (apyrimidinic/apurinic(AP)) lyase reaction at a rate
      approximately equal to that of the glycosylase step. As a generalization of the
      mechanism described for T4 endonuclease V, a repair glycosylase/AP lyase that is
      specific for ultraviolet light-induced cis-syn pyrimidine dimers, a hypothesis
      concerning the mechanism of these repair glycosylases has been proposed. This
      hypothesis describes the initial action of all DNA glycosylases as a nucleophilic
      attack at the sugar C-1' of the damaged base nucleoside, resulting in scission of
      the N-glycosylic bond. It is proposed that the enzymes that are only glycosylases
      differ in the chemical nature of the attacking nucleophile from the
      glycosylase/AP lyases. Those DNA glycosylases, which carry out the AP lyase
      reaction at a rate approximately equal to the glycosylase step, are proposed to
      use an amino group as the nucleophile, resulting in an imino enzyme-DNA
      intermediate. The simple glycosylases, lacking the concomitant AP lyase activity,
      are propose to use some nucleophile from the medium, e.g. an activated water
      molecule. This paper reports experimental tests of this hypothesis using five
      representative enzymes, and these data are consistent with this hypothesis.

PMID- 7642636
TI  - Packaging of proteases and proteoglycans in the granules of mast cells and other
      hematopoietic cells. A cluster of histidines on mouse mast cell protease 7
      regulates its binding to heparin serglycin proteoglycans.
AB  - Mouse mast cell protease 7 (mMCP-7) is a tryptase stored in the secretory
      granules of mast cells. At the granule pH of 5.5, mMCP-7 is fully active and is
      bound to heparin-containing serglycin proteoglycans. to understand the
      interaction of mMCP-7 with heparin inside and outside the mast cell, this trytase
      was first studied by comparative protein modeling. The "pro" form of mMCP-7 was
      then expressed in insect cells and studied by site-directed mutagenesis. Although
      mMCP-7 lacks known linear sequences of amino acis that interact with heparin, the
      three-dimensional model of mMCP-7 revealed an area on the surface of the folded
      protein away from the substrate-binding site that exhibits a strong positive
      electrostatic potential at the acidic pH of the granule. In agreement with this
      calculation, recombinant pro-mMCP-7 bound to a heparin-affinity column at pH 5.5
      and readily dissociated from the column at pH > 6.5. Site-directed mutagenesis
      confirmed the prediction that the conversion of His residues 8,68, and 70 in the
      positively charged region into Glu prevents the binding of pro-mMCP-7 to heparin.
      Because the binding requires positively charged His residues, native mMCP-7 is
      able to dissociate from the protease/proteoglycan macromolecular complex when the
      complex is exocytosed from bone marrow-derived mast cells into a neutral pH
      environment. Many hematopoietic effector cells store positively charged proteins
      in granules that contain serglycin proteoglycans. The heparin/mMCP-7 interaction,
      which depends on the tertiary structure of the tryptase, may be representative of
      a general control mechanism by which hematopoietic cells maximize storage of
      properly folded, enzymatically active proteins in their granules.

PMID- 7642637
TI  - Mutational analysis of the relative orientation of transmembrane helices I and
      VII in G protein-coupled receptors.
AB  - Currently, detailed structural information about the arrangement of the seven
      transmembrane helice (TM I-VII) present in all G protein-coupled receptors is
      still lacking. We demonstrated previously that hybrid m2/m5 muscarinic
      acetylcholine receptors which contain m5 sequence in TM I and m2 sequence in TM
      VII were unable to bind significant amounts of muscarinic radioligands (Pittel,
      Z., and Wess, J. (1994) Mol. Pharmacol. 45, 61-64). By using immunocytochemical
      and enzyme-linked immunosorbent assay techniques, we show in the present study
      that these pharmacologically inactive mutant receptors are present (at high
      levels) on the surface of transfected COS-7 cells. Strikingly, all misfolded
      m2/m5 hybrid receptors could be pharmacologically rescued by introduction of a
      single point mutation into either TM I (m5Thr37--> m2Ala30) or TM VII (m2Thr423-
      > m5His478). All our experimental data are consistent with the notion that the
      two altered threonine residues face each other at the TM 1/TM VII interface in
      the pharmacologically inactive m2/m5 hybrid receptors, thus interfering with
      proper helix-helix packing. Our data provide the first experimental evidence as
      to how TM I and TM VII are oriented relative to each other and also strongly
      suggest that the TM helices in G protein-coupled receptors are arranged in a
      counterclockwise fashion (as viewed from the extracellular membrane surface).

PMID- 7642638
TI  - Ascorbic acid enhances ferritin mRNA translation by an IRP/aconitase switch.
AB  - Replenishment of ascorbate in cultured cells, which are almost uniformly vitamin
      deficient, increases ferritin mRNA translation in response to iron by 20-fold
      (Toth, I., Rogers, J. T., McPhee, J. A., Elliott, S. M., Abramson, S. L., and
      Bridges, K. R. (1995) J. Biol. Chem. 270, 2846-2852). We now demonstrate that
      ascorbate increases cytosolic aconitase activity. The iron-responsive element
      binding protein (IRP-1) exists in three states: bound to mRNA without aconitase
      activity, free in the cytosol without aconitase activity, and free in the cytosol
      with aconitase activity. Ascorbate converts free IRP-1 to the enzymatically
      active form. Enhanced ferritin synthesis with subsequent iron stimulation is due
      to the altered equilibrium of the free IRP-1. The cellular biology of iron is
      closely intertwined with that of ascorbate.

PMID- 7642639
TI  - The C terminus of mitosin is essential for its nuclear localization,
      centromere/kinetochore targeting, and dimerization.
AB  - Mitosin is a novel 350-kDa nuclear phosphoprotein that dramatically relocates
      from the evenly nuclear distribution in S phase to the centromere/kinetochore and
      mitotic apparatus in M phase. The dynamic relocalization of mitosin is
      accompanied by the phosphorylation of itself, suggesting that mitosin plays a
      role in mitotic progression. The molecular basis of nuclear localization and
      targeting of mitosin to the centromere/kinetochore were characterized using a set
      of epitope-tagged deletion mutants. The data indicate that the extreme C terminus
      (amino acids 2,487-3,113) of mitosin has both an independent
      centromere/kinetochore targeting domain and an unusually spaced bipartite nuclear
      localization signal. Moreover, the same centromere/kinetochore targeting domain
      was shown to be essential for the ability of mitosin to bind to itself or other
      putative mitosin-associated proteins through use of the yeast two-hybrid system.
      These results suggest that the C terminus of the mitosin is essential for its
      role in influencing cell cycle progression.

PMID- 7642640
TI  - Activation induces dephosphorylation of cofilin and its translocation to plasma
      membranes in neutrophil-like differentiated HL-60 cells.
AB  - We suggested that a cytosolic 21-kDa phosphoprotein played an important role in
      opsonized zymosan-trigered activation of superoxide-generating enzyme in
      neutrophil-like HL-60 cells through dephosphorylation (Suzuki, K., Yamaguchi, T.,
      Oshizawa, T., Yamamoto, Y., Nishimaki-Mogami, T., Hayakawa, T., and Takahashi, A
      (1995) Biochim. Biophys. Acta 1266, 261-267). In the present study, we
      characterized the phosphoprotein and studied changes in it localization upon
      activation of phagocytes. The 21-kDa phosphoprotein was rapidly dephosphorylated
      upon activation not only wit opsonized zymosan but also with formyl-Met-Leu-Phe
      and arachidonic acid. The peptide fragments derived from the 21-kDa
      phosphoprotein were found to have the same amino acid sequences as those of
      cofilin, an actin-binding protein. The phosphoprotein reacted exclusively with
      anti-cofilin antibody on two dimensional immunoblots. Accordingly, together with
      its apparent molecular weight, isoelectric point, and detection of phosphoserine
      as a phosphoamino acid, we concluded that the 21-kDa phosphoprotein was a
      phosphorylated form of cofilin. The amount of cofilin in membranous fractions was
      increased upon activation. Furthermore, confocal laser scanning microscopy showed
      that cofilin existed diffusely in the cytosol and nuclear region of the resting
      cells, while in the activated cells, it was accumulated at the plasma membrane
      area, forming ruffles or endocytic vesicles on which O2.- should be produced.
      These results suggested that in resting cells cofilin exists as a soluble
      phosphoprotein in the cytosol and nuclei, while upon stimulation a large portion
      of cofilin is dephosphorylated and translocated to the plasma membrane regions.

PMID- 7642641
TI  - SHC and GRB-2 are constitutively by an epidermal growth factor receptor with a
      point mutation in the transmembrane domain.
AB  - A single point mutation, Glu627--> Val, equivalent to the activating mutation in
      the Neu oncogene, was inserted in the transmembrane domain of the human epidermal
      growth factor (EGF) receptor. Unlike the wild type, Glu627-EGF receptor,
      transfected in NIH3T3 cells, gave rise to focal transformation and growth in agar
      even in the absence EGF. Constitutive activity of mutant EGF receptor amounted to
      20% of that of wild type receptor stimulated by EGF. In addition, the mutant
      receptor was more sensitive to EGF, reaching maximum transforming activity at 5
      ng/ml EGF. NIH3T3 cells expressing Glu627-EGF receptor showed a transformed
      phenotype and were not arrested in G0 upon serum deprivation. The mutant receptor
      was constitutively autophosphorylated, and several other cellular proteins were
      phosphorylated on tyrosine in absence of the ligand. Among these, the SHC adaptor
      protein was phosphorylated in absence of EGF, the other adaptor, GRB-2 was
      constitutively associated with the Glu627-EGF receptor in vivo and in vitro, and
      mitogen-activated protein kinase was constitutively phosphorylated. In contrast,
      other EGF receptor substrates, like phospholipase C gamma, were not
      phosphorylated in absence of EGF. The mutant receptor showed a higher sensitivity
      to cleavage by calpain both in absence and presence of EGF, appeared as a 170-
      and 150-kDa doublet in cell extracts, and a specific calpain inhibitor blocked
      the appearance of the 150-kDa form. Since the calpain cleavage site is located in
      the receptor cytoplasmic tail, this finding suggests that the Glu627 mutation
      induces a slightly different conformation in the EGF receptor intracellular
      domain. In conclusion, our data show that a point mutation in the EGF receptor
      transmembrane domain was able to constitutively activate the receptor and to
      induce transformation via constitutive activation of the Ras pathway.

PMID- 7642642
TI  - Molecular cloning of a major cockroach (Blattella germanica) allergen, Bla g 2.
      Sequence homology to the aspartic proteases.
AB  - Inhalation of allergens produced by the German cockroach (Blattella germanica)
      elicits IgE antibody formation and the development of asthma in genetically
      predisposed individuals. We compared the allergenic importance of two cockroach
      (CR) allergens, Bla g 1 and Bla g 2, and determined the complete amino acid
      sequence of the major 36-kDa allergen, Bla g2. A survey of 106 sera from CR
      allergic patients showed the prevalence of IgE antibodies to Bla g 1 and Bla g 2
      to be 30.2% and 57.6%, respectively. Immediate skin tests on 7 selected patients
      gave positive reactions using 10(-3) micrograms/ml either allergen, whereas
      controls showed no response to 10 micrograms/ml. Natural Bla g 2 was purified and
      the sequence of the NH2 terminus and tryptic peptides, comprising 36% of the
      molecule, was determined. The cDNA for Bla g 2 was cloned from a B. germanica
      expression library and encoded a 24-amino acid signal peptide and a 328-amino
      acid mature protein, which showed the highest degree of identity to mosquito
      (Aedes aegypti) lysosomal aspartic protease (30.8%), with similar identity to
      pepsin, cathepsins D and E, renin, and chymosin. Bla g 2 mRNA and protein were
      detected in B. germanica, but not in Periplaneta americana, the other principal
      domiciliary CR species in the U.S. High concentrations of Bla g 2 were found in
      CR digestive organs (esophagus, gut, and proventriculus). The results show that
      Bla g 2 is a major species-specific allergen of B. germanica and suggest that the
      allergen functions as a digestive enzyme in the cockroach.

PMID- 7642643
TI  - Post-transcriptional regulation of human interleukin-2 gene expression at
      processing of precursor transcripts.
AB  - Interleukin-2 (IL-2) regulates the clonal expansion of activated T cells and is
      produced in limited amounts during an immune response. Mitogenic induction of
      human IL-2 gene expression elicits a transient wave of unstable mRNA. We show
      here that transcription continues unabated during and well beyond the time when
      the wave is subsiding, yet few, if any, new mRNA molecules are generated once the
      wave has reached its maximum. Instead, IL-2 precursor transcripts accumulate,
      becoming the majority of expressed IL-2 RNA molecules. The flow of precursor
      transcripts into mature mRNA becomes inhibited in the course of induction. When
      translation is blocked (e.g. by cycloheximide), expression of IL-2 mRNA can be
      superinduced by 2 orders of magnitude. This superinduction is completely
      dependent upon transcription, yet is not accompanied by any significant increase
      in the rate of primary transcription or in mRNA stability. Instead, the
      processing of nuclear IL-2 precursor transcripts is greatly facilitated,
      resulting in pronounced superinduction of cytoplasmic mRNA. Once its
      transcription has been induced, therefore, expression of the IL-2 gene is down
      regulated extensively at the level of precursor RNA processing.

PMID- 7642644
TI  - An active carbonyl formed during glycosylphosphatidylinositol addition to a
      protein is evidence of catalysis by a transamidase.
AB  - Glycosylphosphatidylinositol (GPI) substitution is now recognized to be a
      ubiquitous method of anchoring a protein to membranes in eukaryotes. The
      structure of GPI and its biosynthetic pathways are known and the signals in a
      nascent protein for GPI addition have been elucidated. The enzyme(s) responsible
      for GPI addition with release of a COOH-terminal signal peptide has been
      considered to be a transamidase but has yet to be isolated, and evidence that it
      is a transamidase is indirect. The experiments reported here show that hydrazine
      and hydroxylamine, in the presence of rough microsomal membranes, catalyze the
      conversion of the pro form of the engineered protein miniplacental alkaline
      phosphatase (prominiPLAP) to mature forms from which the COOH-terminal signal
      peptide has been cleaved, apparently at the same site but without the addition of
      GPI. The products, presumable the hydrazide or hydroxamate of miniPLAP, have yet
      to be characterized definitively. However, our demonstration of enzyme-catalyzed
      cleavage of the signal peptide in the presence of the small nucleophiles, even in
      the absence of an energy source, is evidence of an activated carbonyl
      intermediate which is the hallmark of a transamidase.

PMID- 7642645
TI  - Transcriptional activation of the alpha 1(VI) collagen gene during myoblast
      differentiation is mediated by multiple GA boxes.
AB  - During differentiation of ClC12 myoblasts in vitro, expression of alpha 1(VI)
      collagen mRNA was transiently stimulated severalfold. Promoter assays on cells
      transfected with chloramphenicol acetyltransferase (CAT) chimeric constructs have
      identified a region of the alpha 1(VI) a collagen promoter that increases CAT
      activity about 8-fold during differentiation. The region, which overlaps with
      transcription initiation sites, was shown to contain three protected segments (A,
      B, and C) in DNase I footprinting assays. The contact points between nuclear
      factors and the protected segments were determined by methylation interference
      assay and included the sequence GGGAGGG (GA box) in all segments. Experiments in
      which CAT constructs were cotransfected with double-stranded oligonucleotides
      containing the GA box suggested that this motif was necessary for induction.
      Transfections with deletion constructs of the natural promoter and with
      minipromoters made of three copies of A, B, or C showed that the elements have
      inducing activity and that elements C and, to a lower extent, B are stimulatory
      for basal transcription, whereas the contribution of A in this process is
      limited. Electrophoretic mobility shift assays with nuclear extracts from C2C12
      cells indicated that the three GA box-containing elements bound several
      transcription factors, including Sp1. Comparison of the properties of the bands
      shifted under different experimental conditions (presence of 10 mM EDTA, heating
      of the nuclear extracts, addition of different concentrations of competitor
      oligonucleotides) established that A, B, and C probes form nine, eight and five
      main retarded complexes, respectively, and indicated that nuclear factors binding
      to C and B are subsets of proteins binding to A. UV cross-linking assays
      identified several peptides (seven with probe A, six with B, And five with C) in
      the range of 150-32 kDa. Comparison of the gel retardation pattern obtained with
      nuclear extracts from proliferating and differentiating cells revealed a
      particular increased intensity of two retarded bands. The data establish that
      multiple GA boxes mediate induction of the alpha 1(VI) collagen promoter during
      myoblast differentiation and suggest the attractive hypothesis that the effect
      may be related to variations of expression of transcription factors binding to
      these motifs.

PMID- 7642646
TI  - Disassembly of the bacteriophage Mu transposase for the initiation of Mu DNA
      replication.
AB  - Upon catalyzing strand transfer, the Mu transposase (MuA) remains tightly bound
      to the resulting transposition intermediate, the strand transfer complex (STC),
      and poses an impediment to host replication proteins. Additional host factors,
      which can be resolved into two fractions (Mu Replication Factor alpha and beta;
      MRF alpha and MRF beta), are required to disassemble the MuA complex and initiate
      DNA synthesis. MRF alpha modifies the protein content of the STC, removing MuA
      from the DNA in the process. The MRF beta promotes initiation of the Mu DNA
      synthesis on the STC altered by the MRF alpha. These host factors cannot promote
      initiation of Mu DNA synthesis if the STC is damaged by partial proteolysis.
      Moreover, the mutant protein MuA211 cannot be removed from the STC by MRF alpha,
      blocking initiation of DNA synthesis. These results indicate that MuA in the STC
      plays a critical function in beginning a sequence of events leading to the
      establishment of a Mu replication fork.

PMID- 7642647
TI  - Na+, K+, and H+/HCO3- transport in submandibular salivary ducts. Membrane
      localization of transporters.
AB  - The mechanisms mediating transepithelial ion transport in salivary ducts were
      characterized and localized by studying the regulation of [Na+]i, [K+]i, and pHi
      in isolated intralobular ducts and perfused main ducts of the submandibular
      salivary gland. A new procedure was developed for the rapid preparation of
      intralobular ducts. Measurements of pHi revealed the presence of Na+/H+ and Cl
      /HCO3- exchange activities in intralobular duct cells. We could not obtain
      evidence for a coupled K+/H+ exchange activity which was postulated to exist in
      the luminal membrane of duct cells. Rather, a Kout+-dependent pathway which
      mediates the transport of H+/HCO3- and Na+ was found. This pathway was absent
      from acinar cells of the same gland and was active in unstimulated duct cells
      incubated in 5mM Kout+. Accordingly, inhibition of the Na+ pump with ouabain
      resulted in rapid and large Na+ influx in duct but not acinar cells. Perfusion
      experiments with the experimentally accessible main duct and measurements of pHi
      were used to provide the first direct localization of ion transporters in
      salivary ducts. The luminal and basolateral membranes of the duct express
      separate Na+/N+ and Cl-/HCO3- exchangers. Na+/H+ exchange activity in both
      membranes was similar, whereas the luminal Cl-/HCO3- exchange activity was higher
      than that in the basolateral membrane. The perfused main dust was also used to
      localize the newly discovered Kout(+)-dependent H+/HCO3- and Na+ transport
      pathway to the luminal membrane, which suggests that this pathway may play an
      important role in Na+ reabsorption of K+ and HCO3- secretion by the salivary
      ductal system.

PMID- 7642648
TI  - Regulation of [Na+]i in resting and stimulated submandibular salivary ducts.
AB  - In the preceding manuscript (Zhao, H., Xu, X., Diaz, J., and Muallem, S. (1995)
      J. Biol. Chem. 270, 19599-19605), we described a Kout(+)-dependent H+/HCO3- and
      Na+ influx pathway in the luminal membrane of salivary duct cells. In the present
      studies, we further characterized this pathway to show that the Kout(+)-dependent
      Na+ influx was not mediated by the luminal amiloride-sensitive Na+ channel, the
      Na+/H+ exchangers, or any electroneutral or conductive Cl(-)-dependent transport
      pathway. Thus, K+ efflux probably maintained electroneutrality during Na+ influx
      induced by removal of Kout+. Accordingly, Na+ influx was largely inhibited by
      2.5mM external Ba2+. The K+ site of the Kout(+)-dependent Na+ influx showed the
      selectivity sequence Cs+ > K+ > NH4+ >> > Li+ which is different from that of
      several known K+ channels. More importantly, Na+ influx is 50% inhibited at about
      20 mM Kout+, and significant Na+ influx occurred even at 80 mM Kout+. This is a
      critical property for the pathway to play a role in Na+ reabsorption and K+
      secretion by the duct. The large Na+ influx in resting duct cells is matched by
      high activity of the ductal Na+ pump which is about 8-fold faster than that of
      acinar cells. Stimulation of submandibular ducts with various agonists increased
      [Na+]i in an agonist-specific manner. The parasympathetic agonist epinephrine was
      more effective than isoproterenol and sympathetic agonist carbachol. The use of
      various inhibitors of Na+ and K+ transporters suggests that different pathways
      mediate Na+ influx in stimulated acinar and duct cells of the gland. In duct
      cells, Na+ influx was inhibited only by extracellular Cs+ and Ba2+. The overall
      findings support a significant role for the Kout(+)-dependent pathway(s) in Na+
      reabsorption and K+ and HCO3- secretion and explain several features of
      transepithelial electrolyte transport by salivary ducts.

PMID- 7642649
TI  - Interaction of Oct-1 with TFIIB. Implications for a novel response elicited
      through the proximal octamer site of the lipoprotein lipase promoter.
AB  - The ubiquitous human POU domain protein, Oct-1, and the related B-cell protein,
      Oct-2, regulate transcription from a variety of eukaryotic genes by binding to a
      common cis-acting octamer element, 5'-ATTTGCAT-3'. The binding of Oct-1 and Oct-2
      to the functionally important lipoprotein lipase (LPL) promoter octamer site was
      stimulated by the general transcription factor, TFIIB. Comparative analysis of
      the LPL, histone H2B (H2B), and herpes simplex virus ICPO gene promoter octamer
      sites revealed that nucleotide sequences within and flanking the octamer sequence
      determined the degree of TFIIB-mediated stimulation of Oct-1 DNA binding. TFIIB
      was found to decrease the rate of dissociation of Oct-1 from the LPL octamer
      site, whereas it increased the rate of association, as well as decreased the rate
      of dissociation, of Oct-1 from the H2B octamer site. A monoclonal antibody
      against TFIIB immunoprecipitated a ternary complex containing TFIIB, Oct-1, and
      the LPL and H2B octamer binding sites. TFIIB did not alter the DNase I footprints
      generated by Oct-1 on the LPL and H2B promoters. However, Oct-1 on the TATA
      binding protein and TFIIB from footprinting the perfect TATA box sequence located
      5' of the LPL, NF-Y binding site. In transfection experiments, transcription from
      the reporters containing the LPL octamer, and either the SV40 or the yeast
      transcription factor GAL4-dependent enhancers, initiated at a precise position
      within the octamer sequence. Transcription from reporters containing the H2B
      octamer and the SV40 enhancer initiated at several positions within and flanking
      the octamer site, whereas transcription initiated at a precise position within
      the octamer from reporters with both the H2B octamer and the GAL4-dependent
      enhancer. These results suggest that octamers and their flanking sequences play
      an important role in positioning the site of transcription initiation, and that
      this could be a function of the interaction of Oct-1 with TFIIB.

PMID- 7642650
TI  - Transcriptional induction by double-stranded RNA is mediated by interferon
      stimulated response elements without activation of interferon-stimulated gene
      factor 3.
AB  - Many genes induced by type I interferons (IFNs) are also induced by double
      stranded (ds)RAN. In this study, we investigated the mechanism of this induction
      process. Using cell lines from which the type I IFN genes have been deleted, we
      established that induction by dsRNA of the IFN-inducible 561 gene is direct and
      not mediated by the intermediate synthesis of IFN. Unlike 561 mRNA, the IFN
      inducible 6-16 mRNA was induced poorly by dsRNA. Transfection studies
      demonstrated that the sequence difference between the core IFN-stimulated
      response elements (ISREs) of these two genes is not responsible for their
      differential inducibility by dsRNA. A point mutation in the 561 ISRE that
      abolished its response to IFN-alpha also made it unresponsive to dsRNA, thus
      demonstrating that the ISRE is the relevant cis-acting element for dsRNA
      signaling. The roles of different known ISRE-binding protein and tyrosine kinases
      in transducing the signal elicited by dsRNA were evaluated in genetically altered
      cell lines. dsRNA failed to induce 561 mRNA in cells expressing an anti-sense RNA
      for interferon regulatory factor 1, whereas it was induced strongly in cells
      expressing the corresponding sense mRNA. 561 mRNA was also induced strongly by
      dsRNA, but not by IFN-alpha, in mutant cell lines that do not express functional
      tyrosine kinases Tyk2 or JAK1 or ISRE binding protein, p48, or STAT2, all of
      which are required for IFN-alpha signaling. However, in cells devoid of
      functional STAT1, which is also required for IFN-alpha signaling, the induction
      of 561 mRNA by dsRNA was very low. Expression of transfected STAT1 alpha protein,
      but not of STAT 1beta protein, in these cells greatly enhanced the dsRNA
      inducibility of the 561 gene. These studies indicated that the major ISRE
      mediated signaling pathway used by dsRNA requires interferon regulatory factor 1
      and STAT alpha. This pathway, however, does not require the other known
      cytoplasmic components used for IFN-alpha signaling.

PMID- 7642651
TI  - Altered cholesterol trafficking in herpesvirus-infected arterial cells. Evidence
      for viral protein kinase-mediated cholesterol accumulation.
AB  - Herpesvirus infection of arterial smooth muscle cells has been shown to cause
      cholesteryl ester (CE) accumulation. However, the effects of human herpes simplex
      virus type 1 (HSV-1) infection on cholesterol binding and internalization,
      intracellular metabolism, and efflux have not been evaluated. In addition, the
      effects of viral infection on signal transduction pathways that impact upon
      cholesterol metabolism have not been studied. We show in studies reported herein
      that HSV-1 infection of arterial smooth muscle cells enhances low density
      lipoprotein (LDL) binding and uptake which parallels an increase in LDL receptor
      steady state mRNA levels and transcription of the LDL receptor gene. HSV-2 also
      increases CE synthesis and 3-hydroxy- 3-methylglutaryl-CoA reductase activity but
      concomitantly reduces CE hydrolysis and cholesterol efflux. Interestingly, this
      viral infection was associated with a time-dependent decrease in protein kinase A
      activity and an increase in viral-induced protein kinase (VPK) activity
      commensurate with the accumulation of esterified cholesterol. The relationship
      between increased VPK activity and alterations in CE accumulation in virally
      infected cells was explored using an HSV-1 VPK- mutant in which the portion of
      the HSV-1 genome encoding VPK had been deleted. Cholesteryl ester accumulation
      was significantly increased (> 50-fold) in HSV-1-infected cells compared to
      uninfected cells. However, the HSV-1 VPK- mutant had no significant effect on CE
      accumulation. The relationship between VPK activity and these alterations in
      cholesterol metabolism was further supported by the observation that
      staurosporine and calphostin C (protein kinase inhibitors) reduced protein kinase
      activity in HSV-1-infected cells. These results suggest several potential
      mechanisms by which alterations in kinase activities in response to HSV-1
      infection of vascular cells may alter cholesterol trafficking processes that
      eventually lead to CE accumulation.

PMID- 7642652
TI  - Calnexin influences folding of human class I histocompatibility proteins but not
      their assembly with beta 2-microglobulin.
AB  - Class I major histocompatibility complex heavy chains bind to calnexin before
      associating with beta 2-microglobulin (beta 2m) and peptides. Calnexin has been
      shown to retain in the endoplasmic reticulum those class I heavy chains which
      have not assembled properly and, thus, to serve as a quality control mechanism.
      In addition, calnexin may direct the folding of class I subunits or their
      subsequent assembly. We asked whether calnexin plays a role in the initial
      folding of HLA-B*0702 heavy chains by assessing disulfide bond formation in vivo.
      Our results show that class I heavy chains form intrachain disulfide bonds very
      soon after translation, and that calnexin is bound to both reduced and oxidized
      forms during this process. When a cell-permeable reducing agent, dithiothreitol,
      was added to cells, disulfide bond formation in newly synthesized heavy chains
      was substantially blocked, as was their association with calnexin. The reducing
      agent appeared to affect calnexin directly, since binding was similarly abolished
      to a subset of proteins which do not contain internal disulfide bonds. Addition
      of the glucosidase inhibitor castanospermine to cells, shown previously to
      disrupt calnexin binding to ligands, slowed formation of disulfide bonds but did
      not decrease the amount of assembled heavy chain-beta 2m complexes that formed.
      Our data suggest that calnexin can promote disulfide bond formation in class I
      heavy chains but does not directly facilitate subsequent binding to beta 2m.

PMID- 7642653
TI  - Organization of the alpha-globin promoter and possible role of nuclear factor I
      in an alpha-globin-inducible and a noninducible cell line.
AB  - Nuclear factor I (NFI) was suggested to be involved in the expression of the
      human alpha-globin gene. Two established cell lines, which express alpha-globin
      differentially, were therefore compared for differences in binding of NFI at the
      alpha-globin promoter in vivo. HeLa cells, in which alpha-globin is repressed,
      show a high density promoter occupation with several proteins associated with
      structurally distorted DNA. Cell line K562, which is inducible for alpha-globin,
      surprisingly was found to be heterogeneous consisting mainly of cells
      (approximately 95%) unable to express alpha-globin. However, the promoter of the
      nonexpressing K562 cells was clearly different from that of HeLa cells, being
      occupied only at basal transcriptional elements. Therefore, the alpha-globin gene
      in these K562 cells may not be truly repressed, but in an intermediate state
      between repression and active transcription. The NFI site of the alpha-globin
      promoter appeared occupied in HeLa but free of proteins in K562 cells. All cells
      of both cell lines produce NFI, but the composition and DNA binding affinity of
      NFI species differ significantly between the two cell lines. Therefore, distinct
      forms of NFI may repress alpha-globin transcription in HeLa cells. However, NFI
      is apparently not involved in establishing the latent transcriptional state of
      the majority of K562 cells.

PMID- 7642654
TI  - Protein kinase C epsilon subcellular localization domains and proteolytic
      degradation sites. A model for protein kinase C conformational changes.
AB  - Protein kinase C (PCK) epsilon has been found to have unique properties among the
      PCK isozymes in terms of its membrane association, oncogenic potential, and
      substrate specificity. Recently we have demonstrated that PKC epsilon localizes
      to the Golgi network via its zinc finger domain and that both the holoenzyme and
      its zinc finger region modulate Golgi function. To further characterize the
      relationship between the domain organization and the subcellular localization of
      PKC epsilon, a series of NIH 3T3 cell lines were created, each overexpressing a
      different truncated version of PKC epsilon. The overexpressed proteins each were
      designed to contain an epsilon-epitope tag peptide at the COOH terminus to allow
      ready detection with an antibody specific for the tag. The subcellular
      localization of the recombinant proteins was analyzed by in vivo phorbol ester
      binding, immunocytochemistry, and cell fractionation followed by immunoblotting.
      Results revealed several regions of PKC epsilon that contain putative subcellular
      localization signals. The presence either of the hinge region or of a 33-amino
      acid region including the pseudosubstrate sequence in the recombinant proteins
      resulted in association with the plasma membrane and cytoskeletal components. The
      catalytic domain was found predominantly in the cytosolic fraction. The
      accessibility and thus the dominance of these localization signals is likely to
      be affected by the overall conformation of the recombinant proteins. Regions with
      putative proteolytic degradation sites also were identified. The susceptibility
      of the overexpressed proteins to proteolytic degradation was dependent on the
      protein conformation. Based on these observations, a model depicting the
      interaction and hierarchy of the suspected localization signals and proteolytic
      degradation sites is presented.

PMID- 7642655
TI  - Metabolic modulation of transport coupling ratio in yeast plasma membrane H(+)
      ATPase.
AB  - The plasma membrane proton pump (H(+)-ATPase) of yeast energizes solute uptake by
      secondary transporters and regulates cytoplasmic pH. The addition of glucose to
      yeast cells stimulates proton efflux mediated by the H(+)- ATPase. A > 50-fold
      increase in proton extrusion from yeast cells is observed in vivo, whereas the
      ATPase activity of purified plasma membranes is increased maximally 8-fold after
      glucose treatment (Serrano, R. (1983) FEBS Lett. 156, 11-14). The low capacity of
      yeast cells for proton extrusion in the absence of glucose can be explained by
      the finding that, in H(+)-ATPase isolated from glucose-starved cells, ATP
      hydrolysis is essentially uncoupled from proton pumping. The number of protons
      transported per ATP hydrolyzed is significantly increased after glucose
      activation. We suggest that intrinsic uncoupling is an important mechanism for
      regulation of pump activity.

PMID- 7642656
TI  - Interaction of the von Willebrand factor (vWF) with collagen. Localization of the
      primary collagen-binding site by analysis of recombinant vWF A domain
      polypeptides.

PMID- 7642658
TI  - Findings in post-poliomyelitis syndrome. Weakness of muscles of the calf as a
      source of late pain and fatigue of muscles of the thigh after poliomyelitis.
AB  - The purpose of this study was to identify overuse of muscles and other
      alterations in the mechanics of gait in twenty-one patients who had muscular
      dysfunction as a late consequence of poliomyelitis. All of the patients had good
      or normal strength (grade 4 or 5) of the vastus lateralis and zero to fair
      strength (grade 0 to 3) of the calf, as determined by manual testing. Dynamic
      electromyography was used, while the patients were walking, to quantify the
      intensity and duration of contraction of the inferior part of the gluteus
      maximus, the long head of the biceps femoris, the vastus lateralis, and the
      soleus muscles. Patterns of contact of the foot with the floor, temporal-spatial
      parameters, and motion of the knee and ankle were recorded. The principal
      mechanisms of substitution for a weak calf muscle fell into three groups: overuse
      of the quadriceps (twelve patients) or a hip extensor (the inferior part of the
      gluteus maximus in eight patients and the long head of the biceps femoris in
      four), or both; equinus contracture (twelve patients); and avoidance of loading
      response flexion of the knee (five patients). Most patients used more than one
      method of substitution. These observations support the theory that post
      poliomyelitis syndrome results from long-term substitutions for muscular weakness
      that place increased demands on joints, ligaments, and muscles and that treatment
      -based on the early identification of overuse of muscles and ligamentous strain-
      should aim at modification of lifestyle and include use of a brace.

PMID- 7642657
TI  - Enhancement of bone ingrowth by transforming growth factor-beta.
AB  - Enhancement of bone ingrowth with transforming growth factor-beta was evaluated
      in a canine model. Ten dogs had bilateral implantation of a titanium-fiber-metal
      coated rod in the proximal part of the humerus. A three-millimeter gap between
      the outer surface of the porous coating and the surrounding cancellous bone was
      created to impair bone ingrowth. All of the implants were plasma-flame-sprayed
      with hydroxyapatite and tricalcium phosphate. In each animal, one implant was
      also treated with recombinant transforming growth factor-beta 1 while the other
      implant, which was not so treated, served as a paired control. Two doses of
      transforming growth factor-beta 1 were used: 335 micrograms in five animals and
      120 micrograms in the other five. At four weeks, the amount of bone ingrowth in
      the implants that had been treated with 120 micrograms of transforming growth
      factor-beta 1 was threefold higher than that in the paired controls (p = 0.009),
      but with the numbers available there was no significant increase in bone ingrowth
      with the higher dose. The amount of new-bone formation in the three-millimeter
      gaps adjacent to the treated implants was twice that in the gaps of the paired
      controls, regardless of the dose. The differences between the treated and control
      implants with regard to the architecture of the new bone in the gap indicate that
      the mechanism of action of transforming growth factor-beta 1 may include both
      proliferation of osteoprogenitor cells and production of matrix by committed
      osteoblasts. Compared with the findings in a previous study in which this canine
      model was used, the data from the present investigation indicate that enhancement
      of bone ingrowth in implants that have been treated with a combination of a
      hydroxyapatite-tricalcium phosphate coating and transforming growth factor-beta 1
      may exceed that obtainable with grafting of the gap with autogenous cancellous
      bone.

PMID- 7642659
TI  - Prosthetic survival and clinical results with use of large-segment replacements
      in the treatment of high-grade bone sarcomas.
AB  - We evaluated the long-term clinical results and the survival of the prostheses in
      eighty-two patients who had had a limb-sparing procedure by means of the
      implantation of a large-segment prosthesis. All patients had had a high-grade
      bone sarcoma of the distal, middle, or proximal part of the femur; the proximal
      part of the humerus; the proximal part of the tibia; or the pelvis. The duration
      of follow-up ranged from two to twelve years (median, three and one-half years).
      Function was evaluated with the revised 30-point classification system of the
      Musculoskeletal Tumor Society. The survival of the prostheses was analyzed with
      regard to several variables with use of Kaplan-Meier survival estimates. Sixty
      eight patients were alive at the latest follow-up evaluation. The survival rate
      of the prostheses was 83 per cent at five years and 67 per cent at ten years.
      Twelve prostheses were revised, and eleven revisions were successful. The rate of
      revision was highest (six of thirteen) in the patients who had had a tumor of the
      proximal part of the tibia. In contrast, only three (10 per cent) of the thirty
      one patients who had had a tumor of the distal part of the femur and three (10
      per cent) of the twenty-nine who had had a tumor of the proximal part of the
      humerus had a revision. Eleven patients (13 per cent) had an infection, which
      necessitated an amputation in six. Five patients (6 per cent) had a local
      recurrence, and nine patients (11 per cent), including the six already mentioned,
      ultimately needed an amputation. Patients who had had a tumor of the proximal
      part of the humerus had the highest functional scores, while those who had had a
      tumor of the proximal part of the tibia had the lowest scores. Large-segment
      prostheses were a good reconstructive option for the treatment of high-grade bone
      sarcomas in our patients. The rates of long-term survival of the prostheses were
      acceptable and the functional results were good or excellent after this form of
      treatment at most of the anatomical sites at which they were used.

PMID- 7642660
TI  - Strength of the quadriceps femoris muscle and functional recovery after
      reconstruction of the anterior cruciate ligament. A prospective, randomized
      clinical trial of electrical stimulation.
AB  - Immediately after reconstruction of the anterior cruciate ligament, 110 patients
      were randomly assigned to treatment with high-intensity neuromuscular electrical
      stimulation (thirty-one patients), high-level volitional exercise (thirty-four
      patients), low-intensity neuromuscular electrical stimulation (twenty-five
      patients), or combined high and low-intensity neuromuscular electrical
      stimulation (twenty patients). All treatment was performed isometrically with the
      knee in 65 degrees of flexion. All of the patients participated in an intensive
      program of closed-kinetic-chain exercise. After four weeks of treatment, the
      strength of the quadriceps femoris muscle and the kinematics of the knee during
      stance phase were measured. Quadriceps strength averaged 70 per cent or more of
      the strength on the uninvolved side in the two groups that were treated with high
      intensity electrical stimulation (either alone or combined with low-intensity
      electrical stimulation), 57 per cent in the group that was treated with high
      level volitional exercise, and 51 per cent in the group that was treated with low
      intensity electrical stimulation. The kinematics of the knee joint were directly
      and significantly (p < 0.05) correlated with the strength of the quadriceps.
      There was a clinically and statistically significant (p < 0.05) difference in the
      recovery of the quadriceps and the gait parameters according to the type of
      operation that had been performed: the patients who had had reconstruction of the
      anterior cruciate ligament with use of an autologous patellar-ligament graft did
      poorly compared with the other patients.

PMID- 7642661
TI  - Trampoline-related injuries.
AB  - Two hundred and seventeen patients who had sustained an injury during the
      recreational use of a trampoline were managed in the emergency room of Logan
      Regional Hospital in Logan, Utah, from January 1991 through December 1992. We
      retrospectively reviewed the charts and radiographs of these patients to
      categorize the injuries. Additional details regarding the injuries of seventy-two
      patients (33 per cent) were obtained by means of a telephone interview with use
      of a questionnaire. The injuries occurred from February through November, with
      the peak incidence in July. The patients were eighteen months to forty-five years
      old (average, ten years old); ninety-four patients (43 per cent) were five to
      nine years old. Eighty-four patients (39 per cent) sustained a fracture; fifty
      four (25 per cent), a sprain or strain; forty-five (21 per cent), a laceration;
      and thirty-four (16 per cent), a contusion. Fifty-seven injuries (26 per cent)
      involved the elbow or forearm; forty-six (21 per cent), the head or neck; forty
      (18 per cent), the ankle or foot; thirty-three (15 per cent), the knee or leg;
      nineteen (9 per cent), the trunk or back; thirteen (6 per cent), the shoulder or
      arm; and nine (4 per cent), the wrist or hand. Thirteen patients (6 per cent) had
      a back injury, but none of them had a permanent neurological deficit. One patient
      who had an ocular injury was transferred to a tertiary care center. One hundred
      and fifty-six patients (72 per cent) were evaluated radiographically, fifteen (7
      per cent) were admitted to the hospital, and thirteen (6 per cent) had an
      operation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7642662
TI  - Soft-tissue injury as an indication of child abuse.
AB  - We reviewed the hospital records of 371 children who were suspected of having
      been physically abused. Our purpose was to determine specific features that might
      be used to distinguish injuries resulting from abuse from accidental injuries.
      Soft-tissue injuries were found in 341 (92 per cent) of these children.
      Ecchymoses were most common, accounting for 555 (62 per cent) of 892 soft-tissue
      injuries, and very few had a suspicious pattern. Only thirty-four (9 per cent) of
      the children had a radiographically documented fracture, but radiography was
      performed for only thirty-seven (10 per cent) of the patients and it rarely was
      done unless a fracture was clinically obvious. The patterns of injury were age
      specific. The forty-four children who were nine months old or less had an average
      of only one soft-tissue injury; thirty soft-tissue injuries involved the head or
      face, and seven (16 per cent) of the children had a burn. These children were the
      most severely injured: two (5 per cent) died and twenty (45 per cent) had a
      fracture. The sixty-one children who were ten months to two years and eleven
      months old had an average of two soft-tissue injuries; fifty-four soft-tissue
      injuries involved the head or face, and nine (15 per cent) of the children had a
      burn. A fracture was found in eight (13 per cent) of these children.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7642663
TI  - Biomechanical consequences of fracture and repair of the posterior wall of the
      acetabulum.
AB  - We measured the distribution of contact area and pressure between the acetabulum
      and the femoral head of cadaveric pelves in three different conditions: intact,
      with an operatively created fracture of the posterior wall, and after anatomical
      reduction and fixation of the fracture with a buttress plate and interfragmentary
      screws. The study involved eight cadaveric hip joints from five pelves loaded to
      2000 newtons in simulated single-limb stance. Measurements were made with
      pressure-sensitive film. The acetabulum was divided into three areas--the
      anterior wall, the superior aspect, and the posterior wall--for the analysis of
      the data. Creation of a fracture of the posterior wall was followed by an
      increase in contact area, maximum pressure, and contact force in the superior
      aspect of the acetabulum. A concomitant decrease in these parameters was observed
      in the anterior and posterior walls. Anatomical reduction and fixation of the
      fracture with a plate and screws did not restore the pattern of loading to pre
      injury levels.

PMID- 7642664
TI  - Placement of pedicle screws in the thoracic spine. Part I: Morphometric analysis
      of the thoracic vertebrae.
AB  - We studied the morphology of the thoracic vertebrae in the spines of seventeen
      human cadavera in order to define parameters that could be used as guidelines for
      the placement of hooks and screws in the pedicles to obtain internal fixation. We
      also reviewed computerized tomographic scans of nineteen thoracic spines in
      living patients who had no evidence of any vertebral deformity. The transverse
      diameter of the pedicle, which helps to determine the size of the screw, ranged
      from a mean (and standard deviation) of 4.5 +/- 1.2 millimeters in the fourth
      thoracic vertebra to a mean of 7.8 +/- 2.0 millimeters in the twelfth thoracic
      vertebra. The pedicles were inclined anteromedially throughout the thoracic
      spine, and the angle ranged from 0.3 degree toward the midline in the twelfth
      thoracic vertebra to 13.9 degrees in the fourth thoracic vertebra. The
      morphometric data revealed wide variations in the dimensions of the pedicles,
      demonstrating the importance of accurate preoperative imaging with transaxial
      computerized tomographic scans to visualize the precise osseous margins and
      angles of insertion of the thoracic pedicles.

PMID- 7642665
TI  - Placement of pedicle screws in the thoracic spine. Part II: An anatomical and
      radiographic assessment.
AB  - We used computerized tomographic scans and subsequent dissections to evaluate the
      position of ninety pedicle screws that had been inserted bilaterally into the
      fourth through twelfth thoracic vertebrae of five fresh-frozen cadavera. The
      screws had been inserted by five experienced spine surgeons without the use of
      radiographs or imaging studies. Of the ninety screws, thirty-seven were found to
      have penetrated the cortex of the pedicle. Twenty-one screws had penetrated the
      medial cortex and entered the spinal canal, and sixteen had penetrated the
      lateral cortex. The aorta and the esophagus were at greatest risk for injury
      after advancement of the screws beyond the anterior vertebral cortex.
      Computerized tomographic scans of the thoracic spine in nineteen living controls
      who did not have a spinal abnormality confirmed the proximity of the posterior
      mediastinal structures to the misplaced screws.

PMID- 7642666
TI  - Arthrography of the wrist. Assessment of the integrity of the ligaments in young
      asymptomatic adults.
AB  - Fifty-two asymptomatic adults who were between twenty and thirty-five years old
      had arthrography of the wrist with use of a single injection into the radiocarpal
      joint. The purpose of the study was to evaluate the integrity of the triangular
      fibrocartilage, the scapholunate ligament, and the lunotriquetral ligament.
      Contrast medium was injected under fluoroscopic guidance, and posteroanterior and
      lateral radiographs of the wrist were made after the subjects had performed
      exercises of the wrist. No patient who had a history of trauma to the wrist, pain
      in the wrist, or inflammatory arthritis was included in the study. All of the
      subjects had an examination of both upper extremities that included measurement
      of the active motion of the wrist with a goniometer, strength-testing with a
      Jamar dynamometer, ballottement and testing for impingement, and palpation for
      tenderness. Plain radiographs were evaluated, and the ulnar variance was
      recorded. The arthrograms revealed an abnormal communication of the contrast
      medium in fourteen wrists (27 per cent), and four of the fourteen had multiple
      areas of communication. The abnormal communication was through the triangular
      fibrocartilage alone in six wrists, the scapholunate ligament alone in two
      wrists, the lunotriquetral ligament alone in two wrists, and in more than one of
      these areas in four wrists. A positive arthrogram was associated with a greater
      positive ulnar variance. All of the subjects had symmetrical motion of the wrists
      and grip strength, and none of them had tenderness in the wrist. There were no
      complications related to the arthrography. Perforation of a ligament in the wrist
      is common in young asymptomatic adults.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7642667
TI  - Adolescent idiopathic scoliosis. Long-term effect of instrumentation extending to
      the lumbar spine.
AB  - We evaluated eighty-three patients in whom adolescent idiopathic scoliosis had
      been treated with a posterior spinal arthrodesis and Harrington instrumentation
      extending to the second, third, fourth, or fifth lumbar vertebra. All eighty
      three patients completed a questionnaire, and fifty-five patients were also
      examined clinically and roentgenographically at a follow-up evaluation at an
      average of twelve years (range, ten to sixteen years). Twelve patients had a type
      I curve; twenty-six, a type-II curve; sixteen, a type-III curve; and one, a type
      IV curve, according to the classification of King et al. The preoperative Cobb
      angle of the primary curve averaged 60 degrees and ranged from 40 to 100 degrees.
      The curve was an average of 35 degrees (range, 15 to 65 degrees) at the most
      recent follow-up evaluation. Functional assessment with use of information from
      the questionnaire revealed an average spine score of 81 points (range, 18 to 99
      points). On the basis of the score, thirty-five patients were considered to have
      had an excellent result; twenty, a good result; thirteen, a fair result; and
      fifteen, a poor result. Sixty-three (76 per cent) of the eighty-three patients
      had low-back pain compared with thirty (50 per cent) of sixty individuals who
      served as a control group. This difference was significant (p < 0.001; chi-square
      test). Eighteen patients (22 per cent) needed additional spinal procedures.
      Fourteen patients (17 per cent) did not think that the goals of the initial
      operation had been accomplished.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7642668
TI  - Revision total hip arthroplasty without cement: subsidence of proximally porous
      coated femoral components.
AB  - We prospectively studied the intermediate-term results of forty-nine revision
      total hip arthroplasties without cement that were performed because of aseptic
      loosening of a cemented femoral component in forty-five consecutive patients; the
      mean duration of follow-up was sixty-five months (range, forty-five to eighty
      seven months). A curved, long-stem, titanium-alloy, non-circumferentially porous
      coated femoral component was implanted in each hip. Preoperatively, a staging
      system was used to classify deficiencies of femoral bone stock according to the
      loss of cancellous or cortical bone in the metaphysis and diaphysis. Forty-one
      hips (84 per cent) had cortical or ectatic cavitary bone loss in the metaphysis.
      The mean Harris hip score significantly improved from 54 points preoperatively to
      84 points at the time of the latest follow-up examination (p < 0.001). Twenty
      seven patients (twenty-eight hips; 57 per cent) had at least two millimeters of
      subsidence of the femoral component during the first postoperative year. Eight
      patients (eight hips; 16 per cent) had no further progression of subsidence.
      Twenty-one patients (twenty-two hips; 45 per cent) had at least two millimeters
      of subsidence on two separate postoperative evaluations and therefore were
      considered to have progressive subsidence. Seventeen patients (nineteen hips; 39
      per cent) had no measurable subsidence and were considered to have a stable
      femoral component. One of these seventeen patients had had a bilateral femoral
      revision and had progressive subsidence on one side. There was a positive trend
      for an association between subsidence and the degree of preoperative femoral bone
      deficiency (p = 0.10), but there was no association between subsidence and the
      fit of the prosthesis in the metaphysis and diaphysis or the fill of the canal of
      the femur (p > 0.50). There was no significant loss of bone in the hips with
      either a stable or a subsided femoral component (p > 0.50), and qualitative
      reconstitution of the cortex was noted in eleven (52 per cent) of the twenty-one
      most severely deficient (stage-III) femora. Survivorship analysis showed that, at
      seventy-two months, there was a 96 per cent chance of survival of the component
      (95 per cent confidence limits, 0.89 to 1.0) with revision as the end point but
      only a 37 per cent chance of survival (95 per cent confidence limits, 0.15 to
      0.59) with revision or progressive subsidence as the end point.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7642669
TI  - Autogenous bone grafts from the femoral head for the treatment of acetabular
      deficiency in primary total hip arthroplasty with cement. Long-term results.
AB  - Thirty-five consecutive total hip arthroplasties in twenty-eight patients were
      performed with use of cement and insertion of an autogenous graft from the
      femoral head. Five patients (six hips) subsequently died or were lost to follow
      up. The results for the remaining twenty-three patients (twenty-nine hips) were
      reviewed retrospectively at a mean of eleven years (range, seven to seventeen
      years) after the operation. All of the grafts united. The mean estimated coverage
      of the acetabular component by the autogenous graft was 27 per cent (range, 15 to
      45 per cent). Three sockets (10 per cent) were revised because of symptomatic
      loosening without infection at a mean of ten years (eight, ten, and twelve years)
      after the index procedure. All three hips were found to have viable, bleeding
      bone in the region of the remaining graft. An additional eight acetabular
      components had a nonprogressive, asymptomatic, continuous radiolucent line at the
      cement-bone interface. This finding was assumed to indicate loosening of the
      socket, so the total prevalence of loosening was 38 per cent (eleven of twenty
      nine sockets). There was no significant difference between the loose and the well
      fixed components in terms of the amount of coverage by the graft (p > 0.2) or the
      method of fixation (p > 0.4). There was no collapse or resorption of the graft
      that was of mechanical consequence. Autogenous femoral-head bone-grafting is a
      useful technique with a good potential for long-term success when the amount of
      coverage by the graft is limited to less than 40 per cent of the surface of the
      acetabular component.

PMID- 7642670
TI  - Occipitocervical arthrodesis in children. A new technique and analysis of
      results.
AB  - A new wiring technique for occipitocervical arthrodesis was used in sixteen
      consecutive children between 1985 and 1992. The twelve boys and four girls had an
      average age of nine years and six months (range, two years and five months to
      nineteen years and three months) at the operation. The arthrodesis was performed
      between the occiput and the second cervical vertebra in ten patients and between
      the occiput and the third cervical vertebra in six. The instability was related
      to congenital anomalies (six patients), decompression for cervical stenosis (four
      patients), Down syndrome (three patients), trauma (one patient), resection of a
      tumor (one patient), and neurofibromatosis (one patient). Six patients needed a
      laminectomy for decompression because of cervical stenosis or for removal of a
      tumor. All of the patients were managed with an autogenous bone graft from the
      iliac crest and postoperative immobilization with a halo device. Fusion was
      achieved in fifteen of the sixteen patients. Complications developed in seven
      patients. The use of wire fixation, combined with the inherent stability of the
      bone-graft construct, allowed for removal of the halo device relatively early
      (range, six to twelve weeks), before the fusion was fully mature. No graft was
      displaced. All of the patients were followed at least until there was
      radiographic evidence of fusion (fifteen patients) or until a reoperation was
      performed (one patient). The average duration of follow-up was thirty-seven
      months (range, twelve to 108 months).

PMID- 7642671
TI  - Delayed catastrophic rupture of the external iliac artery after an acetabular
      fracture. A case report.

PMID- 7642672
TI  - Increased atlanto-axial instability secondary to an atraumatic fracture of the
      odontoid process in a patient who had rheumatoid arthritis. A case report.

PMID- 7642673
TI  - Synovial sarcoma presenting as an acute compartment syndrome.

PMID- 7642674
TI  - Congenital constricting band with pseudarthrosis of the tibia and fibula. A case
      report.

PMID- 7642675
TI  - Use of allografts after failed treatment of rupture of the anterior cruciate
      ligament.

PMID- 7642676
TI  - The relationship between the design, position, and articular wear of acetabular
      components inserted without cement and the development of pelvic osteolysis.

PMID- 7642677
TI  - Late recognition of a rectal tear associated with a pelvic fracture. A case
      report.

PMID- 7642678
TI  - Interobserver agreement in the classification of open fractures of the tibia. The
      results of a survey of two hundred and forty-five orthopaedic surgeons.

PMID- 7642679
TI  - Physiology of pain.

PMID- 7642680
TI  - Pain assessment versus measurement.

PMID- 7642681
TI  - Pharmacologic management of background pain in burn victims.

PMID- 7642682
TI  - Opioids and analgesia.

PMID- 7642683
TI  - Burn pain: the management of procedure-related pain.
AB  - Burn-related pain is often severe and intermittently excruciating for months
      after the initial injury as the result of the multiple procedures these patients
      must undergo. Procedure-related pain is often undertreated, especially in
      children. Pain management should be integrated into the patient's overall care
      plan. Frequent pain assessment with valid patient self-report measures should be
      the basis for documenting pain treatment efficacy. Pharmacologic methods of pain
      management, including the use of opioids and nonopioid analgesics, are the
      mainstay of pain management. The patient with burns often has altered
      pharmacokinetics and pharmacodynamics to drugs, and these changes must be
      integrated into the use of these agents. In addition, individual patient response
      varies widely, necessitating a highly individualized pain management plan.
      Sedatives, such as benzodiazepines, are often very helpful adjuncts to opioids in
      anxious patients but should not be substituted for analgesics. Psychological
      techniques have proved to be very helpful adjuncts to analgesics but should also
      not be sued as a substitute for analgesics. General anesthesia should be
      considered, especially in children, when patients are to undergo extremely
      painful procedures. Patients need not experience severe pain after burn injury.
      Pain management, especially during very painful procedures, should be an
      integrated part of patients care and high-quality pain management to improve
      patient outcome.

PMID- 7642684
TI  - Chemosensitivity and chemoresistance assays: are they clinically relevant?

PMID- 7642685
TI  - Biotherapy of cancer. Perspectives of immunotherapy and gene therapy.
AB  - Prospects for a new biologically based strategy of cancer treatment are being
      discussed. While physically and chemically based therapies, such as radio- and
      chemotherapy, are not directed against cancer tissue only and have a suppressive
      effect on the immune system, immunotherapy and gene therapy, which are discussed
      here, try to be more selective and to stimulate rather than suppress antitumor
      immune mechanisms. On the basis of personal experience with these new
      technologies, good future prospects are predicted for the application of cancer
      vaccines and immune T lymphocytes for active specific immunization (ASI) and
      adoptive immunotherapy (ADI) respectively. While ASI strategies aim at
      micrometastases being affected by activated host immune T cells, and might find a
      place for postoperative adjuvant treatment in high-risk cancer patients, cellular
      therapies such as ADI do not require an intact host immune system and could
      therefore also find application in advanced stages of disease. In spite of the
      exciting new perspectives of immuno- and gene therapy for the cancer patient,
      this therapy is not yet a defined discipline and requires years of further
      research.

PMID- 7642686
TI  - Comparison of cellular radiosensitivity between different localizations of head
      and neck squamous-cell carcinoma.
AB  - The prognosis of carcinomas arising from various sites in the head and neck
      varies even when the stage of the disease is taken into consideration, e.g.
      laryngeal carcinoma has a more favourable prognosis compared to oral-cavity
      malignancies. The purpose of this study was to evaluate intrinsic cellular
      radiosensitivity as one possible explanation for the observed differences in the
      survival rates of different anatomical groups. The radiation survival curves were
      determined for well characterized cell lines derived from laryngeal carcinoma (n
      = 14), pharyngeal carcinoma (n = 6), carcinoma of the oral cavity (n = 14) and
      the skin of the face (n = 3). The intrinsic radiosensitivity was expressed as
      area under the survival curve (AUC) values, and this cellular parameter was
      compared with clinical data and survival of the patients. The intrinsic
      radiosensitivity in the whole group varied between 1.0 Gy and 2.8 Gy with an
      average of 1.9 Gy. The mean AUC values for the laryngeal cell lines were 2.0 Gy
      +/- 0.2, for the oral cavity 1.8 +/- 0.3 Gy, for the pharynx 1.8 +/- 0.2 Gy and
      for cutaneous carcinoma 2.1 +/- 0.1 Gy. There was a slight difference between the
      groups of glottic and supraglottic cell lines (mean 1.8 +/- 0.2 Gy and 2.1 +/-
      0.3 Gy, respectively), which is consistent with the differences in clinical
      curability of these cancers. Otherwise, the differences in cellular
      radiosensitivity of the carcinoma groups studied did not reach statistical
      significance. These results indicate that the intrinsic radiosensitivity of
      squamous-cell carcinoma (SCC) of the larynx does not significantly differ from
      that of SCC of other sites of the head and neck. Variations in the intrinsic
      radiosensitivity do not as such seem to explain the observed differences in
      radiocurability of SCC variously localized in the head and neck.

PMID- 7642687
TI  - Treatment of human hepatocellular carcinoma by fibroblast-mediated human
      interferon alpha gene therapy in combination with adoptive chemoimmunotherapy.
AB  - The therapeutic effect of the fibroblast-mediated human interferon (IFN alpha)
      gene therapy in combination with interleukin-2 (IL-2) activated killer cells
      (AK)/doxorubicin (i.e., adoptive chemoimmunotherapy) on nude mice bearing the
      human hepatocellular carcinoma (HCC) was investigated. A fibroblast cell clone
      (NIH3T3-IFN alpha+) secreting 1024 U/ml human IFN alpha was obtained from 14
      positive clones by BMGNeo-IFN alpha DNA transfection, G418-resistant selection,
      limiting dilution and assay of IFN alpha activity. After i.p. implantation of
      NIH3T3-IFN alpha+ encapsulated into collagen, serum human IFN alpha activity
      could be detected from 12 h to day 15 with a peak at 72 h. AK were prepared from
      human peripheral mononuclear cells costimulated in vitro by IL-2 and inactivated
      human SMMC 7721 HCC cells. When the NIH3T3-IFN alpha+ cells were i.p. implanted
      into the HCC-bearing nude mice, the grown of HCC was inhibited and the survival
      time of the mice was extended. The growth of HCC was inhibited more obviously
      when AK was i.v. injected and IL-2 was i.p. injected after the NIH3T3-IFN alpha+
      cells had been implanted. The best therapeutic effect was achieved when NIH3T3
      IFN alpha+ cells were used in combination with IL-2/AK/doxorubicin. All these
      results suggested that the fibroblast-mediated human IFN alpha gene therapy could
      be used to treat the human hepatocellular carcinoma effectively and that when
      used in combination with IL-2-based adoptive chemoimmunotherapy, the therapeutic
      effect would be better.

PMID- 7642688
TI  - Influence of zymosan (a non-specific macrophage stimulator) and of indomethacin
      on liver tumours--an experimental study in rats.
AB  - Zymosan--a non-specific macrophage-stimulating agent--reduces tumour take in the
      liver. The mechanism for this effect is not clear, but it may be mediated via the
      Kupffer cells and prostaglandins. On the other hand, the Prostaglandin-synthesis
      inhibitor, indomethacin, inhibits tumour growth. Pretreatment with zymosan (3 mg
      100 g-1) for 3 days of two different strains of rats, inoculated in the liver
      with a hepatoma or an adenocarcinoma cell suspension respectively, reduced tumour
      take and also initial tumour growth. The effect on tumour take and initial growth
      was inhibited by concomitant administration of indomethacin (0.2 mg 100 g-1).
      When zymosan was administered after tumour cell inoculation the growth rate of
      the hepatoma was retarded, but this effect was not abrogated by indomethacin.
      Pretreatment with indomethacin had no significant effect on tumour take or
      initial growth. When given after the tumour was established in the liver,
      indomethacin reduced the growth rate of the hepatoma, but not of the
      adenocarcinoma. These results suggest that there are different mechanisms for the
      effects of zymosan on tumour take and on growth of an established tumour. In
      immunoincompetent nude mice the effect on the hepatoma was similar to the effect
      in the rat. In vitro both tumours were insensitive to zymosan and indomethacin.
      This study confirms that pretreatment with a non-specific macrophage stimulator
      (zymosan) diminishes tumour take and growth in the liver, that the effect of
      zymosan on tumour take in the liver is abrogated by indomethacin and that the
      zymosan effect on tumour take in the liver is at least partly mediated by the
      Kupffer cells and prostaglandins.

PMID- 7642689
TI  - Doxorubicin-heparin complex: reduction of cardiotoxicity of doxorubicin.
AB  - We have compared the antitumor activity and cardiotoxicity of free doxorubicin
      (Dox) and doxorubicin-heparin complex in vivo and in vitro. Dox and Dox-heparin
      complex equally inhibited the DNA synthesis of leukemic cells and showed a
      similar anticancer activity against tumor-bearing mice. Acute toxicity of Dox at
      the dose of 20 mg/kg or 30 mg/kg was significantly more profound than that of the
      Dox-heparin complex, which was demonstrated by survival rate (P < 0.01). Chronic
      toxicities of Dox and the Dox-heparin complex were compared by giving the
      respective reagent (2 mg/kg) weekly for 20 weeks. The weight gains of the mice
      given Dox-heparin complex were greater than those of the mice given Dox alone (P
      < 0.01). The pathological damage to the cardiac tissue in mice treated with Dox
      heparin complex was significantly less severe than that of mice treated with Dox.
      Thus, the present study indicates that complexing with heparin diminished the
      acute and chronic toxicity of Dox without reducing its antitumor activity in
      mice, and suggests a possible clinical application of Dox-heparin complex in
      humans.

PMID- 7642690
TI  - Effect of cisplatin in advanced colorectal cancer resistant to 5-fluorouracil
      plus (S)-leucovorin.
AB  - Modulation of 5-fluorouracil (5-FU) is currently being investigated in advanced
      colorectal cancer. In an attempt to improve the results obtainable for the
      association of 5-FU and leucovorin, we decided to add cisplatin to 5-FU and (6S)
      leucovorin (S-LV) after disease progression. The hypothesis was that a
      pharmacological enhancement of the efficacy of 5-FU would result in responses in
      5-FU-unresponsive patients or in a second response in previously responding
      patients. A group of 28 5-FU+S-LV-pretreated patients, with advanced measurable
      colorectal cancer, were treated with 80 mg/m2 cisplatin on day 1, 80 mg/m2 S-LV
      and 370 mg/m2 5-FU as an i. v. bolus for 5 consecutive days every 4 weeks. We
      obtained 3 partial responses (response rate: 11 +/- 11%), while 11 patients had
      stable disease (39 +/- 18%). Among the 3 responders, 1 patient had earlier
      achieved a partial response, a second stable disease and 1 had disease
      progression after the previous 5-FU+S-LV treatment. The median survival time for
      all 28 patients was 11 months. Toxicity was minimal and consisted of mild and
      reversible gastrointestinal symptoms and myelosuppression. We believe that
      further studies must be carried out to establish the real impact of the synergism
      between cisplatin, 5-FU and S-LV in untreated patients.

PMID- 7642691
TI  - The use of the Calvert formula to determine the optimal carboplatin dosage.
AB  - Carboplatin is a chemotherapeutic agent frequently used in the treatment of
      various malignancies. The myelotoxicity and clinical efficacy of carboplatin
      correlate with the clearance of the drug, which is correlated to the glomerular
      filtration rate (GFR). Dosing of this agent based solely upon the patients body
      surface area is therefore not accurate enough; the GFR, and thus the clearance of
      carboplatin differ in each patient irrespective of the body area. Consequently,
      some patients undergo a higher systemic exposure, expressed as the area under the
      plasma concentration/time curve (AUC), than others when dosages of carboplatin
      are given on the basis of the body surface area. A high AUC correlates with
      increased toxicity, thus increasing the risks of the treatment, but in the case
      of a low AUC the therapeutical efficacy decreases. This indicates that an
      individual dosing strategy is warranted to obtain the optimal AUC. In this
      article, the development and application of a simple equation, known as the
      Calvert formula, are discussed. This formula can be used to calculate the
      carboplatin dose accurately in order to obtain a target AUC by using only the
      GFR. The formula is: dose (mg) = AUC (mg ml-1 min) x [GFR (ml/min) + 25
      (ml/min)]. This formula has proven to be, in both retrospective and prospective
      studies, a reliable tool to calculate the optimal dose of carboplatin Future
      studies should determine the value of the creatinine clearance as a measure for
      the GFR.

PMID- 7642692
TI  - Workshop: active specific immunotherapy with tumor cell vaccines. Heidelberg,
      Germany, November 1994.

PMID- 7642693
TI  - Thirty-first annual meeting of the American Society of Clinical Oncology. Los
      Angeles, California, 20-23 May 1995.

PMID- 7642694
TI  - Large and small splice variants of collagen XII: differential expression and
      ligand binding.
AB  - Collagen XII has a short collagenous tail and a very large, three-armed NC3
      domains consisting primarily of fibronectin type III repeats. Differential
      splicing within this domain gives rise to a large (320 kD) and a small (220 kD)
      subunit; the large but not the small can carry glycosaminoglycan. To investigate
      whether collagen XII variants have distinct expression patterns and functions, we
      generated antibody and cDNA probes specific for the alternatively spliced domain.
      We report here that the large variant has a more restricted expression in
      embryonic tissue than the small. For example, whereas the small variant is
      widespread in the dermis, the large is limited to the base of feather buds.
      Distinct proportions of mRNA for the two variants were detected depending on the
      tissue. Monoclonal antibodies allowed us to separate collagen XII variants, and
      to show that homo- and heterotrimers exist. Collagen XII variants differ in
      ligand binding. Small subunits interact weakly with heparin via their COOH
      terminal domain. Large subunits have additional, stronger heparin-binding site(s)
      in their NH2-terminal extra domain. In vivo, both large and small collagen XII
      are associated with interstitial collagen. Here we show biochemically and
      ultrastructurally that collagen XII can be incorporated into collagen I fibrils
      when it is present during, but not after, fibril formation. Removal of the
      collagenous domain of collagen XII reduces its coprecipitation with collagen I.
      Our results indicate that collagen XII is specifically associated with fibrillar
      collagen, and that the large variant has binding sites for extracellular ligands
      not present in the small variant.

PMID- 7642695
TI  - Early events in DNA replication require cyclin E and are blocked by p21CIP1.
AB  - Using immunodepletion of cyclin E and the inhibitor protein p21WAF/CIP1, we
      demonstrate that the cyclin E protein, in association with Cdk2, is required for
      the elongation phase of replication on single-stranded substrates. Although
      cyclin E/Cdk2 is likely to be the major target by which p21 inhibits the
      initiation of sperm DNA replication, p21 can inhibit single-stranded replication
      through a mechanism dependent on PCNA. While the cyclin E/Cdk2 complex appears to
      have a role in the initiation of DNA replication, another Cdk kinase, possibly
      cyclin A/Cdk, may be involved in a later step controlling the switch from
      initiation to elongation. The provision of a large maternal pool of cyclin E
      protein shows that regulators of replication are constitutively present, which
      explains the lack of a protein synthesis requirement for replication in the early
      embryonic cell cycle.

PMID- 7642696
TI  - Retention of glucose units added by the UDP-GLC:glycoprotein glucosyltransferase
      delays exit of glycoproteins from the endoplasmic reticulum.
AB  - It has been proposed that the UDP-Glc:glycoprotein glucosyltransferase, an
      endoplasmic reticulum enzyme that only glucosylates improperly folded
      glycoproteins forming protein-linked Glc1Man7-9-GlcNAc2 from the corresponding
      unglucosylated species, participates together with lectin-like chaperones that
      recognize monoglucosylated oligosaccharides in the control mechanism by which
      cells only allow passage of properly folded glycoproteins to the Golgi apparatus.
      Trypanosoma cruzi cells were used to test this model as in trypanosomatids
      addition of glucosidase inhibitors leads to the accumulation of only
      monoglucosylated oligosaccharides, their formation being catalyzed by the UDP
      Glc:glycoprotein glucosyltransferase. In all other eukaryotic cells the
      inhibitors produce underglycosylation of proteins and/or accumulation of
      oliogosaccharides containing two or three glucose units. Cruzipain, a lysosomal
      proteinase having three potential N-glycosylation sites, two at the catalytic
      domain and one at the COOH-terminal domain, was isolated in a glucosylated form
      from cells grown in the presence of the glucosidase II inhibitor 1
      deoxynojirimycin. The oligosaccharides present at the single glycosylation site
      of the COOH-terminal domain were glucosylated in some cruzipain molecules but not
      in others, this result being consistent with an asynchronous folding of
      glycoproteins in the endoplasmic reticulum. In spite of not affecting cell growth
      rate or the cellular general metabolism in short and long term incubations, 1
      deoxynojirimycin caused a marked delay in the arrival of cruzipain to lysosomes.
      These results are compatible with the model proposed by which monoglucosylated
      glycoproteins may be transiently retained in the endoplasmic reticulum by lectin
      like anchors recognizing monoglucosylated oligosaccharides.

PMID- 7642697
TI  - Role for phosphatidylinositol 3-kinase in the sorting and transport of newly
      synthesized lysosomal enzymes in mammalian cells.
AB  - Previous work with the yeast Saccharomyces cerevisiae has demonstrated a role for
      a phosphatidylinositol-specific PI 3-kinase, the product of the VPS34 gene, in
      the targeting of newly synthesized proteins to the vacuole, an organelle
      functionally equivalent to mammalian lysosomes (Schu, P. V., K. Takegawa, M. J.
      Fry, J. H. Stack, M. D. Waterfield, and S. D. Emr. 1993. Science [Wash. DC].
      260:88-91). The activity of Vps34p kinase is significantly reduced by the PI 3
      kinase inhibitors wortmannin, a fungal metabolite, and LY294002, a quercetin
      analog (Stack, J. H., and S. D. Emr. 1994. J. Biol. Chem. 269:31552-31562). We
      show here that at concentrations which inhibit VPS34-encoded PI 3-kinase
      activity, wortmannin also inhibits the processing and delivery of newly
      synthesized cathepsin D to lysosomes in mammalian cells with half-maximal
      inhibition of delivery occurring at 100 nM wortmannin. As a result of wortmannin
      action, newly synthesized, unprocessed cathepsin D is secreted into the media.
      Moreover, after accumulation in the trans-Golgi network (TGN) at 20 degrees C,
      cathepsin D was rapidly missorted to the secretory pathway after addition of
      wortmannin and shifting to 37 degrees C. At concentrations that inhibited
      lysosomal enzyme delivery, both wortmannin and LY294002 caused a highly specific
      dilation of mannose 6-phosphate receptor (M6PR)-enriched vesicles of the
      prelysosome compartment (PLC), which swelled to approximately 1 micron within 15
      min after treatment. With increasing time, the inhibitors caused a significant
      yet reversible change in M6PR distribution. By 3 h of treatment, the swollen PLC
      vacuoles were essentially depleted of receptors and, in addition, there was a
      fourfold loss of receptors from the cell surface. However, M6PRs were still
      abundant in the TGN. These results are most consistent with the interpretation
      that PI 3-kinase regulates the trafficking of lysosomal enzymes by interfering
      with a M6PR-dependent sorting event in the TGN. Moreover, they provide evidence
      that trafficking of soluble hydrolases to mammalian lysosomes and yeast vacuoles
      rely on similar regulatory mechanisms.

PMID- 7642698
TI  - Wortmannin causes mistargeting of procathepsin D. evidence for the involvement of
      a phosphatidylinositol 3-kinase in vesicular transport to lysosomes.
AB  - At present little is known of the biochemical machinery controlling transport of
      newly synthesized lysosomal hydrolases from the trans-Golgi network (TGN) to
      endosomes. The demonstration that Vps34p (a protein required for targeting
      soluble hydrolases to the vacuole in Saccharomyces cerevisiae) is a
      phosphatidylinositol 3-kinase (PI3-K) suggested the possibility that a homologous
      enzyme might be involved in the equivalent step in mammalian cells. Using the PI3
      K inhibitors wortmannin and LY294002, I provide evidence to support this
      hypothesis. Treatment of K-562 cells with wortmannin induced secretion of
      procathepsin D, with half-maximal inhibition of accurate targeting to lysosomes
      at 10-20 nM. Kinetic analysis indicated that a late Golgi (TGN) step was
      affected, and that other constitutive vesicular transport events were not. The
      M6P recognition signal was still generated in the presence of wortmannin
      suggesting that the drug was directly inhibiting export of the receptor-ligand
      complex from the TGN, while removal of the drug led to a rapid restoration of
      accurate sorting. At the concentrations used, wortmannin and LY294002 are
      presently accepted to be specific inhibitors of PI3-K. I conclude that these data
      implicate such an enzyme in the trafficking of M6P-receptor-ligand complexes from
      the TGN towards lysosomes.

PMID- 7642699
TI  - Intracellular sorting and targeting of melanosomal membrane proteins:
      identification of signals for sorting of the human brown locus protein, gp75.
AB  - The structural and functional integrity of cytoplasmic organelles is maintained
      by intracellular mechanisms that sort and target newly synthesized proteins to
      their appropriate cellular locations. In melanocytic cells, melanin pigment is
      synthesized in specialized organelles, melanosomes. A family of melanocyte
      specific proteins, known as tyrosinase-related proteins that regulate melanin
      pigment synthesis, is localized to the melanosomal membrane. The human brown
      locus protein, tyrosinase-related protein-1 or gp75, is the most abundant
      glycoprotein in melanocytic cells, and is a prototype for melanosomal membrane
      proteins. To investigate the signals that allow intracellular retention and
      sorting of glycoprotein (gp)75, we constructed protein chimeras containing the
      amino-terminal extracellular domain of the T lymphocyte surface protein CD8, and
      transmembrane and cytoplasmic domains of gp75. In fibroblast transfectants,
      chimeric CD8 molecules containing the 36-amino acid cytoplasmic domain of gp75
      were retained in cytoplasmic organelles. Signals in the gp75 cytoplasmic tail
      alone, were sufficient for intracellular retention and targeting of the chimeric
      proteins to the endosomal/lysosomal compartment. Analysis of subcellular
      localization of carboxy-terminal deletion mutants of gp75 and the CD8/gp75
      chimeras showed that deletion of up amino acids from the gp75 carboxyl terminus
      did not affect intracellular retention and sorting, whereas both gp75 and
      CD8/gp75 mutants lacking the carboxyl-terminal 27 amino acids were transported to
      the cell surface. This region contains the amino acid sequence, asn-gln-pro-leu
      leu-thr, and this hexapeptide is conserved among other melanosomal proteins.
      Further evidence showed that this hexapeptide sequence is necessary for
      intracellular sorting of gp75 in melanocytic cells, and suggested that a signal
      for sorting melanosomal proteins along the endosomal/lysosomal pathway lies
      within this sequence. These data provide evidence for common signals for
      intracellular sorting of melanosomal and lysosomal proteins, and support the
      notion that lysosomes and melanosomes share a common endosomal pathway of
      biogenesis.

PMID- 7642700
TI  - Transport from late endosomes to lysosomes, but not sorting of integral membrane
      proteins in endosomes, depends on the vacuolar proton pump.
AB  - Endocytosed proteins are sorted in early endosomes to be recycled to the plasma
      membrane or transported further into the degradative pathway. We studied the role
      of endosomes acidification on the endocytic trafficking of the transferrin
      receptor (TfR) as a representative for the recycling pathway, the cation
      dependent mannose 6-phosphate receptor (MPR) as a prototype for transport to late
      endosomes, and fluid-phase endocytosed HRP as a marker for transport to
      lysosomes. Toward this purpose, bafilomycin A1 (Baf), a specific inhibitor of the
      vacuolar proton pump, was used to inhibit acidification of the vacuolar system.
      Microspectrofluorometric measurement of the pH of fluorescein-rhodamine
      conjugated transferrin (Tf)-containing endocytic compartments in living cells
      revealed elevated endosomal pH values (pH > 7.0) within 2 min after addition of
      Baf. Although recycling of endocytosed Tf to the plasma membrane continued in the
      presence of Baf, recycled Tf did not dissociate from its receptor, indicating
      failure of Fe3+ release due to a neutral endosomal pH. In the presence of Baf,
      the rates of internalization and recycling of Tf were reduced by a factor of 1.40
      +/- 0.08 and 1.57 +/- 0.25, respectively. Consequently, little if any in TfR
      expression at the cell surface was measured during Baf treatment. Sorting between
      endocytosed TfR and MPR was analyzed by the HRP-catalyzed 3,3'-diaminobenzidine
      cross-linking technique, using transferrin conjugated to HRP to label the
      endocytic pathway of the TfR. In the absence of Baf, endocytosed surface 125I
      labeled MPR was sorted from the TfR pathway starting at 10 min after uptake,
      reaching a plateau of 40% after 45 min. In the presence of Baf, sorting was
      initiated after 20 min of uptake, reaching approximately 40% after 60 min.
      Transport of fluid-phase endocytosed HRP to late endosomes and lysosomes was
      measured using cell fractionation and immunogold electron microscopy. Baf did not
      interfere with transport of HRP to MPR-labeled late endosomes, but nearly
      completely abrogated transport to cathepsin D-labeled lysosomes. From these
      results, we conclude that trafficking through early and late endosomes, but not
      to lysosomes, continued upon inactivation of the vacuolar proton pump.

PMID- 7642701
TI  - A truncated form of the Pho80 cyclin redirects the Pho85 kinase to disrupt
      vacuole inheritance in S. cerevisiae.
AB  - Partitioning of the vacuole during cell division in Saccharomyces cerevisiae
      begins during early S phase and ends in late G2 phase before the yeast nucleus
      migrates into the bud neck. We have isolated and characterized a new mutant, vac5
      1, which is defective in vacuole segregation. Cells with the vac5-1 mutation can
      form large buds without vacuoles. The VAC5 gene was cloned and is identical to
      PHO80. PHO80 encodes a cyclin which acts in a complex with a cdc-like kinase,
      PHO85, as a negative regulator of two transcription factors (PHO2 and PHO4) that
      govern the expression of metabolic phosphatases. The vacuole inheritance defect
      in vac5-1 cells is dependent on the presence of the Pho85 kinase and its targets
      Pho4p and Pho2p. As with other alleles of PHO80, phosphatase levels are elevated
      in vac5-1 mutants. A suppressor, the COOH-terminal half of the Gal11
      transcription factor, rescues the vac5-1 phenotype of defective vacuole
      inheritance without altering the vac5-1 phenotype of elevated phosphatase levels.
      In addition, neither maximal nor minimal levels of expression of the inducible
      "PHO" system phosphatases causes a vacuole inheritance defect. Though vac5-1 is
      recessive, pho80 delta or pho85 delta strains do not show a defect in vacuole
      inheritance, suggesting that vac5-1 is not a complete loss-of-function allele.
      Sequence analysis shows that the vac5-1 allele encodes a truncated form of the
      Pho80 cyclin and overexpression of vac5-1 in pho80 delta cells causes a vacuole
      inheritance defect. We conclude that the vac5-1 allele directs the Pho85 kinase
      to regulate, via transcription factors Pho4 and Pho2, genes that affect vacuole
      inheritance but which are not known to be under normal PHO pathway control.

PMID- 7642702
TI  - Overexpression of calreticulin increases the Ca2+ capacity of rapidly exchanging
      Ca2+ stores and reveals aspects of their lumenal microenvironment and function.
AB  - A molecularly tagged form of calreticulin (CR), a low affinity-high capacity Ca2+
      binding protein that resides in the ER lumen, was transiently transfected into
      HeLa cells to specifically modify the Ca2+ buffering capacity of the
      intracellular Ca2+ stores. Fluorescence and confocal microscope
      immunocytochemistry revealed the tagged protein to be expressed by over 40% of
      the cells and to overlap in its distribution the endogenous CR yielding a
      delicate cytoplasmic network, i.e., the typical pattern of ER. In contrast, no
      signal was observed associated with the plasmalemma (marked by ConA) and within
      the nucleus. One- and two-dimensional Western blots revealed the transfected to
      exceed the endogenous CR of approximately 3.5-fold and to maintain its Ca2+
      binding ability, whereas the expression of other ER proteins was unchanged. Ca2+
      homeostasis in the transfected cells was investigated by three parallel
      approaches: (a) 45Ca equilibrium loading of cell populations; (b) [Ca2+]c
      measurement with fura-2 followed by quantitative immunocytochemistry of single
      cells and iii) [Ca2+]c measurement of cell population upon cotransfection with
      the Ca(2+)-sensitive photoprotein, aequorin. The three approaches revealed
      different aspects of Ca2+ homeostasis, yielding results which were largely
      complementary. In particular, the following conclusions were established: (a)
      both endogenous and transfected CR participate in Ca2+ buffering within the IP3
      sensitive, rapidly exchanging, Ca2+ stores; the other pools of the cells were in
      contrast unaffected by CR transfection; (b) the Ca2+ capacity of the stores is
      not the main limiting factor of individual IP3-mediated Ca2+ release responses
      triggered by receptor agonists; (c) in control cells, the contribution of CR to
      Ca2+ buffering within the IP3-sensitive stores accounts for approximately 45% of
      the total, the rest being probably contributed by the other lumenal (and also
      membrane) Ca2+ binding proteins; (d) the free [Ca2+] within the lumen of the IP3
      sensitive stores, revealed by the degree of Ca2+ binding to the transfected CR
      protein, amounts to values in (or approaching) the millimolar range; and (e) Ca2+
      influx across the plasmalemma activated by depletion of the stores is directly
      dependent on the lumenal [Ca2+].

PMID- 7642703
TI  - Inositol 1,4,5-trisphosphate receptors selectively localized to the acrosomes of
      mammalian sperm.
AB  - Calcium flux is required for the mammalian sperm acrosome reaction, an exocytotic
      event triggered by egg binding, which results in a dramatic rise in sperm
      intracellular calcium. Calcium-dependent membrane fusion results in the release
      of enzymes that facilitate sperm penetration through the zona pellucida during
      fertilization. We have characterized inositol 1,4,5-trisphosphate (IP3)-gated
      calcium channels and upstream components of the phosphoinositide signaling system
      in mammalian sperm. Peptide antibodies colocalized G alpha q/11 and the beta 1
      isoform of phospholipase C (PLC beta 1) to the anterior acrosomal region of mouse
      sperm. Western blotting using a polyclonal antibody directed against purified
      brain IP3 receptor (IP3R) identified a specific 260 kD band in 1% Triton X-100
      extracts of rat, hamster, mouse and dog sperm. In each species, IP3R
      immunostaining localized to the acrosome cap. Scatchard analysis of [3H]IP3
      binding to rat sperm sonicates revealed a curvilinear plot with high affinity (Kd
      = 26 nM, Bmax = 30 pmol/mg) and low affinity (Kd = 1.6 microM, Bmax = 550
      pmol/mg) binding sites, reflecting among the highest receptor densities in
      mammalian tissue. Immunoelectron microscopy confirmed the acrosomal localization
      in rat sperm. The IP3R fractionated with acrosomes by discontinuous sucrose
      gradient centrifugation and was enriched in the medium of acrosome-reacted sperm.
      ATP-dependent 45Ca2+ loading of digitonin permeabilized rat sperm was decreased
      by 45% in the presence of 10 microM IP3. The IP3-mediated release of calcium was
      blocked by heparin. Thapsigargin, a sequiterpene lactone inhibitor of the
      microsomal Ca(2+)-ATPase, stimulated the acrosome reaction of mouse sperm to the
      same extent as the Ca2+ ionophore, A23187. The failure of caffeine and ryanodine
      to affect calcium accumulation suggested that thapsigargin acted through an IP3
      sensitive store. The presence of G alpha q/11, PLC beta 1 and a functional IP3R
      in the anterior acrosomal region of mammalian sperm, as well as thapsigargin's
      induction of the acrosome reaction, implicate IP3-gated calcium release in the
      mammalian acrosome reaction.

PMID- 7642704
TI  - Maintenance of the differentiated state in skeletal muscle: activation of v-Src
      disrupts sarcomeres in quail myotubes.
AB  - We have used quail skeletal myotubes expressing a temperature-sensitive allele of
      the v-src oncogene to address the issue of the homeostasis of sarcomeric
      myofibrils in differentiated muscle cells. Reactivation of the v-Src tyrosine
      kinase by shifting the cultures to the permissive temperature leads within
      minutes to the formation of F-actin-containing bodies (ABs), that originate in
      the ventral region of the myotubes and increase in number concomitantly with the
      dismantling of the I-Z-I complex of the sarcomeres. This process is detailed by
      confocal and electron microscopy. Indirect immunofluorescence reveals that ABs
      contain muscle-specific protein isoforms associated with the I-Z-I complexes and
      vinculin, a component of the cytoskeletal network. Anti-phosphotyrosine
      antibodies label proteins in ABs and Z-discs. Evidence is presented indicating
      that this phenomenon specifically depends on the persistent activation of v-Src,
      rather than on a general increase in phosphotyrosine content such as that induced
      by vanadate. AB formation is prevented by activation of protein kinase C by
      phorbol ester or by treatment with the kinase inhibitor 2-aminopurine, without
      any detectable effect on tyrosine phosphorylation. Taken together these findings
      indicate that phosphorylation of specific target proteins by v-Src, although
      necessary, is not sufficient per se to induce AB formation. In addition, the
      signal transduction cascade that culminates in MAP kinase activation and its
      nuclear translocation is activated both by v-Src and phorbol ester, and is
      relatively unaffected by 2-aminopurine. These findings imply that both phorbol
      esters and 2-aminopurine operate, at least in part, at the level of alternative
      pathways that may diverge upstream of the MAP kinase and are presumably mediating
      the early effects of v-Src on the differentiated phenotype.

PMID- 7642706
TI  - Rigidity of microtubules is increased by stabilizing agents.
AB  - Microtubules are rigid polymers that contribute to the static mechanical
      properties of cells. Because microtubules are dynamic structures whose
      polymerization is regulated during changes in cell shape, we have asked whether
      the mechanical properties of microtubules might also be modulated. We measured
      the flexural rigidity, or bending stiffness, of individual microtubules under a
      number of different conditions that affect the stability of microtubules against
      depolymerization. The flexural rigidity of microtubules polymerized with the
      slowly hydrolyzable nucleotide analogue guanylyl-(alpha, beta)-methylene
      diphosphonate was 62 +/- 9 x 10(-24) Nm2 (weighted mean +/- SEM); that of
      microtubules stabilized with tau protein was 34 +/- 3 x 10(-24) Nm2; and that of
      microtubules stabilized with the antimitotic drug taxol was 32 +/- 2 x 10(-24)
      Nm2. For comparison, microtubules that were capped to prevent depolymerization,
      but were not otherwise stabilized, had a flexural rigidity of 26 +/- 2 x 10(-24)
      Nm2. Decreasing the temperature from 37 degrees C to approximately 25 degrees C,
      a condition that makes microtubules less stable, decreased the stiffness of taxol
      stabilized microtubules by one-third. We thus find that the more stable a
      microtubule, the higher its flexural rigidity. This raises the possibility that
      microtubule rigidity may be regulated in vivo. In addition, the high rigidity of
      an unstabilized, GDP-containing microtubule suggests that a large amount of
      energy could be stored as mechanical strain energy in the protein lattice for
      subsequent force generation during microtubule depolymerization.

PMID- 7642705
TI  - Mechanochemistry of protein 4.1's spectrin-actin-binding domain: ternary complex
      interactions, membrane binding, network integration, structural strengthening.
AB  - Mechanical strength of the red cell membrane is dependent on ternary interactions
      among the skeletal proteins, spectrin, actin, and protein 4.1. Protein 4.1's
      spectrin-actin-binding (SAB) domain is specified by an alternatively spliced exon
      encoding 21 amino acid (aa) and a constitutive exon encoding 59 aa. A series of
      truncated SAB peptides were engineered to define the sequences involved in
      spectrin-actin interactions, and also membrane strength. Analysis of in vitro
      supramolecular assemblies showed that gelation activity of SAB peptides
      correlates with their ability to recruit a critical amount of spectrin into the
      complex to cross-link actin filaments. Also, several SAB peptides appeared to
      exhibit a weak, cooperative actin-binding activity which mapped to the first 26
      residues of the constitutive 59 aa. Fluorescence-imaged microdeformation was used
      to show SAB peptide integration into the elastic skeletal network of spectrin,
      actin, and protein 4.1. In situ membrane-binding and membrane-strengthening
      abilities of the SAB peptides correlated with their in vitro gelation activity.
      The findings imply that sites for strong spectrin binding include both the
      alternative 21-aa cassette and a conserved region near the middle of the 59 aa.
      However, it is shown that only weak SAB affinity is necessary for physiologically
      relevant action. Alternatively spliced exons can thus translate into strong
      modulation of specific protein interactions, economizing protein function in the
      cell without, in and of themselves, imparting unique function.

PMID- 7642707
TI  - A molecular marker for centriole maturation in the mammalian cell cycle.
AB  - The centriole pair in animals shows duplication and structural maturation at
      specific cell cycle points. In G1, a cell has two centrioles. One of the
      centrioles is mature and was generated at least two cell cycles ago. The other
      centriole was produced in the previous cell cycle and is immature. Both
      centrioles then nucleate one procentriole each which subsequently elongate to
      full-length centrioles, usually in S or G2 phase. However, the point in the cell
      cycle at which maturation of the immature centriole occurs is open to question.
      Furthermore, the molecular events underlying this process are entirely unknown.
      Here, using monoclonal and polyclonal antibody approaches, we describe for the
      first time a molecular marker which localizes exclusively to one centriole of the
      centriolar pair and provides biochemical evidence that the two centrioles are
      different. Moreover, this 96-kD protein, which we name Cenexin (derived from the
      Latin, senex for "old man," and Cenexin for centriole) defines very precisely the
      mature centriole of a pair and is acquired by the immature centriole at the G2/M
      transition in prophase. Thus the acquisition of Cenexin marks the functional
      maturation of the centriole and may indicate a change in centriolar potential
      such as its ability to act as a basal body for axoneme development or as a
      congregating site for microtubule-organizing material.

PMID- 7642708
TI  - Kinetochore chemistry is sensitive to tension and may link mitotic forces to a
      cell cycle checkpoint.
AB  - Some cells have a quality control checkpoint that can detect a single misattached
      chromosome and delay the onset of anaphase, thus allowing time for error
      correction. The mechanical error in attachment must somehow be linked to the
      chemical regulation of cell cycle progression. The 3F3 antibody detects
      phosphorylated kinetochore proteins that might serve as the required link
      (Gorbsky, G. J., and W. A. Ricketts. 1993. J. Cell Biol. 122:1311-1321). We show
      by direct micromanipulation experiments that tension alters the phosphorylation
      of kinetochore proteins. Tension, whether from a micromanipulation needle or from
      normal mitotic forces, causes dephosphorylation of the kinetochore proteins
      recognized by 3F3. If tension is absent, either naturally or as a result of
      chromosome detachment by micromanipulation, the proteins are phosphorylated.
      Equally direct experiments identify tension as the checkpoint signal: tension
      from a microneedle on a misattached chromosome leads to anaphase (Li, X., and R.
      B. Nicklas. 1995. Nature (Lond.). 373:630-632), and we show here that the absence
      of tension caused by detaching chromosomes from the spindle delays anaphase
      indefinitely. Thus, the absence of tension is linked to both kinetochore
      phosphorylation and delayed anaphase onset. We propose that the kinetochore
      protein dephosphorylation caused by tension is the all clear signal to the
      checkpoint. The evidence is circumstantial but rich. In any event, tension alters
      kinetochore chemistry. Very likely, tension affects chemistry directly, by
      altering the conformation of a tension-sensitive protein, which leads directly to
      dephosphorylation.

PMID- 7642709
TI  - The checkpoint delaying anaphase in response to chromosome monoorientation is
      mediated by an inhibitory signal produced by unattached kinetochores.
AB  - During mitosis in Ptk1 cells anaphase is not initiated until, on average, 23 +/-
      1 min after the last monooriented chromosome acquires a bipolar attachment to the
      spindle--an event that may require 3 h (Rieder, C. L., A. Schultz, R. W. Cole,
      and G. Sluder. 1994. J. Cell Biol. 127:1301-1310). To determine the nature of
      this cell-cycle checkpoint signal, and its site of production, we followed PtK1
      cells by video microscopy prior to and after destroying specific chromosomal
      regions by laser irradiation. The checkpoint was relieved, and cells entered
      anaphase, 17 +/- 1 min after the centromere (and both of its associated sister
      kinetochores) was destroyed on the last monooriented chromosome. Thus, the
      checkpoint mechanism monitors an inhibitor of anaphase produced in the centromere
      of monooriented chromosomes. Next, in the presence of one monooriented
      chromosome, we destroyed one kinetochore on a bioriented chromosome to create a
      second monooriented chromosome lacking an unattached kinetochore. Under this
      condition anaphase began in the presence of the experimentally created
      monooriented chromosome 24 +/- 1.5 min after the nonirradiated monooriented
      chromosome bioriented. This result reveals that the checkpoint signal is not
      generated by the attached kinetochore of a monooriented chromosome or throughout
      the centromere volume. Finally, we selectively destroyed the unattached
      kinetochore on the last monooriented chromosome. Under this condition cells
      entered anaphase 20 +/- 2.5 min after the operation, without congressing the
      irradiated chromosome. Correlative light microscopy/elctron microscopy of these
      cells in anaphase confirmed the absence of a kinetochore on the unattached
      chromatid. Together, our data reveal that molecules in or near the unattached
      kinetochore of a monooriented PtK1 chromosome inhibit the metaphase-anaphase
      transition.

PMID- 7642710
TI  - Local neurotrophic repression of gene transcripts encoding fetal AChRs at rat
      neuromuscular synapses.
AB  - The spatio-temporal expression patterns of mRNA transcripts coding for
      acetylcholine receptor (AChR) subunits and myogenic factors were measured in
      denervated rat soleus muscle and in soleus muscle chronically paralyzed for up to
      12 d by conduction block of the sciatic nerve by tetrodotoxin (TTX). In
      denervated muscle the AChR alpha-, beta-, gamma-, and delta-subunit mRNAs were
      elevated with highest expression levels in the former synaptic and the
      perisynaptic region and with lower levels in the extrasynaptic fiber segments. In
      muscle paralyzed by nerve conduction block the alpha-, beta-, gamma-, and delta
      subunit mRNA levels increased only in extrasynaptic fiber segments. Surprisingly,
      in the synaptic region the gamma-subunit mRNA that specifies the fetal-type AChR,
      and alpha-, beta-, delta-subunit mRNAs were not elevated. The expression of the
      gene encoding the epsilon-subunit, which specifies the adult-type AChR, was
      always restricted to synaptic nuclei. The mRNA for the regulatory factor myogenin
      showed after denervation similar changes as the subunit transcripts of the fetal
      AChR. When the muscle was paralyzed by nerve conduction block the increase of
      myogenin transcripts was also less pronounced in synaptic regions compared to
      extrasynaptic fiber segments. The results suggest that in normal soleus muscle a
      neurotrophic signal from the nerve locally down-regulates the expression of fetal
      type AChR channel in the synaptic and perisynaptic muscle membrane by inhibiting
      the expression of the gamma-subunit gene and that inhibition of the myogenin gene
      expression may contribute to this down-regulation.

PMID- 7642711
TI  - Developmental regulation of membrane traffic organization during synaptogenesis
      in mouse diaphragm muscle.
AB  - In innervated adult skeletal muscles, the Golgi apparatus (GA) displays a set of
      remarkable features in comparison with embryonic myotubes. We have previously
      shown by immunocytochemical techniques, that in adult innervated fibers, the GA
      is no longer associated with all the nuclei, but appears to be concentrated
      mostly in the subneural domain under the nerve endings in chick (Jasmin, B. J.,
      J. Cartaud, M. Bornens, and J.-P. Changeux. 1989. Proc. Natl. Acad. Sci. USA.
      86:7218-7222) and rat (Jasmin, B. J., C. Antony, J.-P. Changeux, and J. Cartaud.
      1995. Eur. J. Neurosci. 7:470-479). In addition to such compartmentalization,
      biochemical modifications take place that suggest a functional specialization of
      the subsynaptic GA. Here, we focused on the developmental regulation of the
      membrane traffic organization during the early steps of synaptogenesis in mouse
      diaphragm muscle. We investigated by immunofluorescence microscopy on
      cryosections, the distribution of selected subcompartments of the exocytic
      pathway, and also of a representative endocytic subcompartment with respect to
      the junctional or extrajunctional domains of developing myofibers. We show that
      throughout development the RER, the intermediate compartment, and the
      prelysosomal compartment (mannose 6-phosphate receptor-rich compartment) are
      homogeneously distributed along the fibers, irrespective of the subneural or
      extrajunctional domains. In contrast, at embryonic day E17, thus 2-3 d after the
      onset of innervation, most GA markers become restricted to the subneural domain.
      Interestingly, some Golgi markers (e.g., alpha-mannosidase II, TGN 38, present in
      the embryonic myotubes) are no longer detected in the innervated fiber even in
      the subsynaptic GA. These data show that in innervated muscle fibers, the distal
      part of the biosynthetic pathway, i.e., the GA, is remodeled selectively shortly
      after the onset of innervation. As a consequence, in the innervated fiber, the GA
      exists both as an evenly distributed organelle with basic functions, and as a
      highly differentiated subsynaptic organelle ensuring maturation and targeting of
      synaptic proteins. Finally, in the adult, denervation of a hemidiaphragm causes a
      burst of reexpression of all Golgi markers in extrasynaptic domains of the
      fibers, hence showing that the particular organization of the secretory pathway
      is placed under nerve control.

PMID- 7642712
TI  - Fish E587 glycoprotein, a member of the L1 family of cell adhesion molecules,
      participates in axonal fasciculation and the age-related order of ganglion cell
      axons in the goldfish retina.
AB  - Axons derived from young ganglion cells in the periphery of the retinae of larval
      and adult goldfish are known to fasciculate with one another and their immediate
      forerunners, creating the typical age-related order in the retinotectal pathway.
      Young axons express the E587 antigen, a member of the L1 family of cell adhesion
      molecules. Repeated injections of Fab fragments from a polyclonal E587 antiserum
      (E587 Fabs) into the eye of 3.4 cm goldfish disrupted the orderly fascicle
      pattern of RGC axons in the retina which was preserved in controls. Instead of
      bundling tightly, RGC axons crossed one another, grew between fascicles and
      arrived at the optic disk in a broadened front. When added to RGC axons growing
      in vitro, E587 Fabs neutralized the preference of growth cones to elongate on
      lanes of E587 protein, caused defasciculation of axons which normally prefer to
      grow along each other when explanted on polylysine, and prevented clustering of
      E587 antigen at axon-axon contact sites. Monoclonal E587 antibody disturbed
      axonal fasciculation moderately but led to a 30% reduction in growth velocities
      when axons tracked other axons. Therefore we conclude that E587 antigen mediates
      axonal recognition, selective fasciculation and the creation of the age-related
      order in the fish retina.

PMID- 7642714
TI  - Transfected connexin45 alters gap junction permeability in cells expressing
      endogenous connexin43.
AB  - Many cells express multiple connexins, the gap junction proteins that
      interconnect the cytosol of adjacent cells. Connexin43 (Cx43) channels allow
      intercellular transfer of Lucifer Yellow (LY, MW = 443 D), while connexin45
      (Cx45) channels do not. We transfected full-length or truncated chicken Cx45 into
      a rat osteosarcoma cell line ROS-17/2.8, which expresses endogenous Cx43. Both
      forms of Cx45 were expressed at high levels and colocalized with Cx43 at plasma
      membrane junctions. Cells transfected with full-length Cx45 (ROS/Cx45) and cells
      transfected with Cx45 missing the 37 carboxyl-terminal amino acids (ROS/Cx45tr)
      showed 30-60% of the gap junctional conductance exhibited by ROS cells.
      Intercellular transfer of three negatively charged fluorescent reporter molecules
      was examined. In ROS cells, microinjected LY was transferred to an average of
      11.2 cells/injected cell, while dye transfer between ROS/Cx45 cells was reduced
      to 3.9 transfer between ROS/Cx45 cells was reduced to 3.9 cells. In contrast,
      ROS/Cx45tr cells transferred LY to > 20 cells. Transfer of calcein (MW = 623 D)
      was also reduced by approximately 50% in ROS/Cx45 cells, but passage of
      hydroxycoumarin carboxylic acid (HCCA; MW = 206 D) was only reduced by 35% as
      compared to ROS cells. Thus, introduction of Cx45 altered intercellular coupling
      between cells expressing Cx43, most likely the result of direct interaction
      between Cx43 and Cx45. Transfection of Cx45tr and Cx45 had different effects in
      ROS cells, consistent with a role of the carboxyl-terminal domain of Cx45 in
      determining gap junction permeability or interactions between connexins. These
      data suggest that coexpression of multiple connexins may enable cells to achieve
      forms of intercellular communication that cannot be attained by expression of a
      single connexin.

PMID- 7642713
TI  - Receptor protein tyrosine phosphatase PTPmu associates with cadherins and
      catenins in vivo.
AB  - The extracellular segment of the receptor-type type protein tyrosine phosphatase
      PTPmu, possesses an MAM domain, an immunoglobulin domain, and four fibronectin
      type-III repeats. It binds homophilically, i.e., PTPmu on the surface of one cell
      binds to PTPmu on an apposing cell, and the binding site lies within the
      immunoglobulin domain. The intracellular segment of PTPmu has two PTP domains and
      a juxtamembrane segment that is homologous to the conserved intracellular domain
      of the cadherins. In cadherins, this segment interacts with proteins termed
      catenins to mediate association with the actin cytoskeleton. In this article, we
      demonstrate that PTPmu associates with a complex containing cadherins, alpha- and
      beta-catenin in mink lung (MvLu) cells, and in rat heart, lung, and brain
      tissues. Greater than 80% of the cadherin in the cell is cleared from Triton X
      100 lysates of MvLu cells after immunoprecipitation with antibodies to PTPmu;
      however, the complex is dissociated when lysates are prepared in more stringent,
      SDS-containing RIPA buffer. In vitro binding studies demonstrated that the
      intracellular segment of PTPmu binds directly to the intracellular domain of E
      cadherin, but not to alpha- or beta-catenin. Consistent with their ability to
      interact in vivo, PTPmu, cadherins, and catenins all localized to points of cell
      cell contact in MvLu cells, as assessed by immunocytochemical staining. After
      pervanadate treatment of MvLu cells, which inhibits cellular tyrosine phosphatase
      activity including PTPmu, the cadherins associated with PTPmu are now found in a
      tyrosine-phosphorylated form, indicating that the cadherins may be an endogenous
      substrate for PTPmu. These data suggest that PTPmu may be one of the enzymes that
      regulates the dynamic tyrosine phosphorylation, and thus function, of the
      cadherin/catenin complex in vivo.

PMID- 7642716
TI  - Sequence-specific DNA binding activities of nuclear matrix proteins of mammalian
      lens epithelial cells.
AB  - This study examines matrix and nonmatrix nuclear proteins of the rabbit lens
      epithelial cells. The nuclear matrix proteins were isolated by modified Penman
      technique, which requires presence of detergents and nucleases, whereas nonmatrix
      nuclear proteins were obtained by high salt extraction. The data from these
      experiments revealed presence of DNA binding activities for SP-1 and OCT-1
      proteins in both matrix and non-matrix compartments of rabbit lens epithelial
      cells. Comparison of the relative abundance of SP-1 and OCT-1 binding activities
      in nuclear matrix and nonmatrix fractions suggest the distribution between these
      two compartments is cell type specific and possibly related to the control of
      cell growth.

PMID- 7642715
TI  - Hst-1 (FGF-4) antisense oligonucleotides block murine limb development.
AB  - The initiation of limb development depends on the site specific proliferation of
      the mesenchyme by the signals from the apical ectodermal ridge (AER) in embryonic
      mouse. We have previously reported that the local expression of Hst-1/Fgf-4
      transcripts in AER of the mouse limb bud is developmentally regulated, expressed
      at 11 and 12 days post coitus (p.c.) embryo. In an effort to further understand
      the role of Hst-1/FGF-4 in mouse limb development, an antisense
      oligodeoxynucleotides (ODNs) study was performed. We first established a novel
      organ culture system to study mouse limb development in vitro. This system allows
      mouse limb bud at 9.5-10-d p.c. embryo, when placed on a sheet of extracellular
      matrix in a defined medium, to differentiate into a limb at 12.5-d p.c. embryo
      within 4.5 d. Using this organ culture system, we have shown that exposure of 9.5
      10-d p.c. embryonal limb bud explants to antisense ODNs of Hst-1/FGF-4 blocks
      limb development. In contrast, sense and scrambled ODNs have no inhibitory effect
      on limb outgrowth, suggesting that Hst-1/FGF-4 may work as a potent inducing
      factor for mouse limb development.

PMID- 7642717
TI  - Intranuclear binding of nucleoplasmin.
AB  - Many proteins--including not only structural proteins, but also enzymes, hormone
      receptors, and other transcription factors--accumulate to much higher nuclear
      than cytoplasmic concentrations. Nuclear localization sequences or signals (NLSs)
      within their primary structures entrain specific transport of these proteins
      through the nuclear pore complexes. This transport process is energy-dependent,
      but evidence for a true active transport mechanism is not conclusive. An
      alternative mechanism--facilitated transport of NLS proteins followed by their
      intranuclear binding--has been implicated by experiments with oil-isolated
      nuclei. However, there has been no agreement as to a role for binding in the in
      vivo nuclear accumulation of NLS-containing proteins. We demonstrate herein that
      a prototypical NLS protein, nucleoplasmin (Np), binds within the nucleus of the
      living Xenopus oocyte and that this binding accounts for its nuclear
      accumulation.

PMID- 7642718
TI  - 5'phosphorylation of DNA in mammalian cells: identification of a polymin P
      precipitable polynucleotide kinase.
AB  - Proteins that catalyze 5' phosphorylation of an oligodeoxyribonucleotide
      substrate can be fractionated by polymin P treatment of whole cell extracts of
      calf thymus glands. Anion exchange chromatography on Q-Sepharose revealed three
      separable peaks of activity in the polymin P supernatant fraction, and one peak
      of activity in the Polymin P pellet fraction. The latter activity, Polymin P
      precipitable polynucleotide kinase (PP-PNK), was further purified with a 1,500
      fold increase of specific activity compared to the crude Polymin P pellet
      fraction. Oligonucleotides, a dephosphorylated 2.9-kb EcoRI fragment, and poly(A)
      were phosphorylated by the enzyme preparation, but thymidine 3' monophosphate was
      not a substrate. PP-PNK preparations exhibited an apparent KM of 52 microM for
      ATP and 8 microM for oligo dT25. The enzyme preparation displayed no detectable
      3' phosphatase or cyclic 2',3' phosphohydrolase activities. The sedimentation
      coefficient of the PP-PNK activity was 3.8S as determined by sucrose density
      gradient analysis; the Stokes radius was 45 A, leading to an estimated molecular
      mass of 72 kDa. The enzyme had a pH optimum in the neutral to alkaline range in
      several buffer systems and is distinct from the DNA kinase with an acidic pH
      optimum previously described in calf thymus.

PMID- 7642719
TI  - 1 alpha,25-Dihydroxyvitamin D3 rapidly alters phospholipid metabolism in the
      nuclear envelope of osteoblasts.
AB  - 1 alpha,25-Dihydroxyvitamin D3 (1 alpha,25-(OH)2D3) has been shown to increase
      cytosolic calcium and inositol triphosphate levels in rat osteosarcoma cells (ROS
      17/2.8) and to increase nuclear calcium in these cells. To determine the
      mechanism(s) of 1 alpha,25-(OH)2D3-induced changes in nuclear calcium, the effect
      of the hormone on phospholipid metabolism in isolated osteoblast nuclei was
      assessed. 1 alpha,25(OH)2D3, 20 nM, increased inositol triphosphate levels in the
      nuclei after 5 min of treatment. The biologically inactive epimer, 1 beta,25
      (OH)2D3, had no significant effect on inositol triphosphate levels. ATP, 1 mM,
      also increased inositol triphosphate levels in the isolated nuclei after 5 min. 1
      alpha,25-(OH)2D3, 20 nM, increased calcium in the isolated nuclei in the presence
      but not in the absence of extranuclear calcium within 5 min. Nuclear calcium was
      also increased within 5 min by ATP, 1 mM, and inositol triphosphate, 1 mM. The
      effect of ATP on nuclear calcium was not additive with 1 alpha,25-(OH)2D3,
      suggesting that these two agents increase nuclear calcium in these osteoblast
      like cells by similar mechanisms. In summary, 1 alpha,25-(OH)2D3 and ATP rapidly
      increase inositol triphosphate levels in nuclei isolated from ROS 17/2.8 cells.
      The hormone, the nucleotide, and the inositol phospholipid increase nuclear
      calcium. Thus, the 1 alpha,25-(OH)2D3 and ATP effects on nuclear calcium may be
      mediated by changes in phospholipid metabolism in the nuclei of these osteoblast
      like cells.

PMID- 7642720
TI  - Myoblast and myotube nuclei display similar patterns of heterogeneous
      acetylcholine receptor subunit mRNA expression.
AB  - Muscle progenitor cells differentiate to myoblasts, and subsequently myotubes,
      upon expression of muscle specific genes. We and others have previously shown
      that myotube nuclei, even in the absence of nerve, express AChR alpha subunit RNA
      at varying levels, with a small subset (about ten percent) of the nuclei
      expressing at high levels. These findings raised two important questions: 1) is
      the observed heterogeneity a unique property of the alpha subunits, and 2) when
      does the heterogeneity begin? In particular, is it induced only at or after the
      time of fusion, or does it exist at the myoblast stage? We have, therefore,
      extended our observations to the gamma and delta subunits and we also have
      examined the distributions of AChR alpha, gamma, and delta subunit RNAs in both
      myoblasts and myotubes. We used intron and intron-exon probes to detect
      prespliced transcripts or mature mRNAs in the cells. Because intron-containing
      transcripts are not transported out of the nuclei, the distributions of these
      transcripts can indicate their expression patterns among nuclei in the same
      myotubes. Our results show that both myotubes and myoblasts have distributions of
      the AChR alpha, gamma, and delta subunit RNAs which differ sharply from that of
      the U1 RNA or Myo D. Thus, the heterogeneous expression of AChR genes is not only
      an intrinsic property of muscle cell nuclei (in the sense that it does not
      require the presence of nerves), but it also exists prior to fusion. Our results
      suggest that muscle nuclei attain individualized capacities for AChR subunit mRNA
      production early in their development. Conceptual models consistent with such
      individuality imply an additional level of regulation beyond the known diffusible
      transcriptional factors.

PMID- 7642722
TI  - Unidirectional potentiation of binding between two anti-FBP MAbs: evaluation of
      the involved mechanisms.
AB  - The monoclonal antibody MOv19 directed to a folate binding protein shows
      temperature-dependent potentiation of binding of the noncompeting monoclonal
      antibody MOv18 to the relevant antigen, but the mechanism involved in this
      phenomenon had remained unclear. Use of chimeric versions of both monoclonal
      antibodies and the F(ab')2 and Fab fragments of MOv19 revealed an increment in
      MOv18 binding in all combinations irrespective of the origin of the Fc portion of
      the monoclonal antibody. The potentiating effect of bivalent MOv19 fragments on
      125I-MOv18 binding was similar to that of the entire monoclonal antibody and
      occurred at saturating concentrations of both reagents at which monovalent
      binding prevails. Similarly, the monovalent fragment also induced a significant
      increase in MOv18 binding. However, the potentiation occurred only at very high
      concentrations of antibody fragment. Homologous inhibition was drastically
      reduced using MOv19 Fab fragment, suggesting a low binding stability of the
      monovalent reagent. Immunoblotting analysis and binding in the presence of
      exogenous purified folate binding protein indicated a cross-linking between
      soluble and cell surface molecules mediated by the bivalent monoclonal
      antibodies. The extent of the increase in MOv18 binding at 0 degrees C with high
      amounts of exogenous folate binding protein was lower than that obtained at 37
      degrees C in the absence of added molecule. Release of 125I-MOv18 from the cell
      surface was significantly higher in the absence of MOv19 than in its
      presence.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7642721
TI  - Zeolite A inhibits osteoclast-mediated bone resorption in vitro.
AB  - The effects of Zeolite A on bone resorbing activity of highly purified avian
      osteoclasts were analyzed. The present study demonstrates that when 100
      micrograms/ml of acid-treated Zeolite A is added to the media the number of pits
      per osteoclast is reduced 3-fold at 24 h after treatment. Secreted cathepsin B
      enzyme activity was also reduced 3-fold. A similar reduction in pit number per
      osteoclast was measured following 48 h of treatment with Zeolite A but there
      appeared to be less reduction of cathepsin B enzyme activity. The effects on pit
      number and cathepsin B protein activity were Zeolite dose dependent. The
      structure of the compound seemed to be responsible for the effects measured since
      compounds used to represent constituents of Zeolite A (silicon dioxide and
      aluminum chloride) failed to inhibit bone resorption or reduce the level of
      secreted cathepsin B enzyme activity. Thus the molecular architecture of Zeolite
      A or a derivative thereof appears to be important. In conclusion, the data
      indicate that Zeolite A can inhibit bone resorption. Together with previous data
      on osteoblasts, this might suggest a potential positive activity of intact
      Zeolite A or a partial substructure of Zeolite A on bone turnover.

PMID- 7642723
TI  - Molecular anatomy of an endodermal gland: investigations on mucus glycoproteins
      and cell turnover in Brunner's glands of Didelphis virginiana using lectins and
      PCNA immunoreactivity.
AB  - Brunner's glands are located in the submucosa of the proximal duodenum and are
      unique to mammalian species. The North American opossum (Didelphis virginiana) is
      generally regarded as a prototype marsupial that closely resembles fossil
      didelphids which can be placed at the beginning of mammalian evolution. The
      current investigation provided an opportunity for the analysis of secretory
      products from these glands in a species thought to be more closely related to
      earlier evolutionary forms. Extracts of Brunner's glands were subjected to SDS
      PAGE and Western blotting. The results indicate the presence of two high
      molecular weight PAS-positive glycoprotein bands. In addition to these two PAS
      positive bands, several other glycoprotein bands were detected in the high
      molecular weight range that bind several lectins which typically recognize O
      linked carbohydrates indicative of mucus type glycoproteins. The same lectins
      bind to glandular structures in tissue sections. Comparison of lectin binding
      sites with the pyloric glands of the stomach and duodenal goblet cells indicates
      that Brunner's glands carbohydrate residues resemble those of the pyloric glands
      more closely than those of the duodenal goblet cells. The low cell turnover rate
      in Brunner's glands is in contrast to the rapid turnover rate of goblet cell
      precursors in the duodenal crypts. The mucus composition and the cell turnover
      rate correlate well with embryological data and suggest that Brunner's glands of
      Didelphis evolved from an epithelium more closely associated with the stomach
      than that of the duodenum as the topography of the gland would suggest.

PMID- 7642725
TI  - Expression of gamma-glutamyl transpeptidase by renal epithelial cells occurs on a
      cell-by-cell basis and is inhibited by chronic TPA treatment.
AB  - Upon attaining a confluent density, populations of the renal epithelial cell
      line, LLC-PK1, express progressively many properties characteristic of the renal
      proximal tubule cell, including gamma-glutamyl transpeptidase activity.
      Expression of transpeptidase activity was inhibited reversibly by chronic
      treatment with the phorbol ester tumor promoter, 12-O-tetradecanoylphorbol-13
      acetate (TPA). TPA treatment inhibited expression of transpeptidase activity
      regardless of whether added prior to or following appearance of the activity.
      Increased transpeptidase activity in postconfluent cell populations was due to an
      increased enzyme Vmax with no change in substrate Km. TPA-treated cell
      populations exhibited a low Vmax similar to subconfluent populations. Detection
      of transpeptidase activity at the individual cell level by enzyme histochemistry
      demonstrated that near-confluent cell populations possessed few transpeptidase
      activity-positive cells. Progressive expression of transpeptidase activity in the
      cell population was due to an increasing proportion of cells in the population
      possessing transpeptidase activity. There was a parallel increase in the
      proportion of cells expressing transpeptidase protein, detected by
      immunofluorescence. TPA treatment inhibited appearance of both transpeptidase
      activity and transpeptidase protein in virtually all cells of the population.
      These results demonstrate that expression of transpeptidase activity in
      populations of LLC-PK1 cells occurs on a cell-by-cell basis and reflects
      expression of transpeptidase protein. Chronic treatment with TPA inhibits
      reversibly expression of transpeptidase activity and protein, suggesting a role
      for protein kinase C in regulating expression of this proximal tubule-specific
      property.

PMID- 7642724
TI  - Developmental changes in the activity and cellular localization of hepatic casein
      kinase II in the rat.
AB  - The activity and cellular localization of hepatic casein kinase II (CKII) was
      examined during late fetal development in the rat. Cultured fetal hepatocytes
      displayed constitutive CKII activity which was not further activated by growth
      factor exposure. Similarly, fetal liver CKII showed approximately fivefold
      greater activity than adult liver. The fetal hepatic activity was, to a large
      degree, localized to a nuclear fraction. Postnuclear cytosol preparations from
      fetal and adult liver showed similar CKII activity. In all cases, FPLC ion
      exchange chromatography followed by Western immunoblotting showed that
      immunoreactive CKII coincided with kinase activity. However, parallel
      determinations of CKII activity and immunoreactive CKII levels showed a higher
      (five- to sixfold) CKII specific activity in nuclear extracts compared to
      cytosol. In summary, fetal hepatic CKII demonstrates coincident nuclear
      localization and activation. We hypothesize that the regulation of hepatic CKII
      is relevant to the mitogen-independent proliferation displayed by fetal rat
      hepatocytes.

PMID- 7642726
TI  - Influence of protein tyrosine phosphorylation on the expression of the c-myc
      oncogene in cancer of the large bowel.
AB  - We tested the potential impact of tyrosine phosphorylation on the expression of
      the c-myc gene in two colon cancer cell lines, HCT8 and SW837. We found that the
      protein tyrosine kinase inhibitor genistein causes a decrease in the abundance of
      c-myc RNA and an inhibition of proliferation with a similar dose response.
      Geldanamycin, a mechanistically different tyrosine kinase inhibitor, also causes
      a decrease in both the expression of c-myc RNA and proliferation. Genistein has
      also been found to inhibit topoisomerase II, but the topoisomerase II inhibitor
      novobiocin did not lower the expression of c-myc. The most likely interpretation
      is that inhibition of protein tyrosine kinase activity caused a decrease in c-myc
      expression in these cells. The impact of tyrosine phosphorylation on the
      expression of the c-myc gene is further supported by the finding that inhibition
      of phosphotyrosine phosphatase using orthovanadate causes an increase in the
      level of c-myc RNA. The effect of genistein on HCT8 cells is not dependent on the
      synthesis of new protein and does not involve an alteration in the stability of
      the message. Analysis of transcription in the c-myc gene reveals a more
      complicated picture with a decrease in initiation and an increase in elongation
      but no net change in transcription. We speculate that the genistein induced
      reduction in myc expression is the result of a posttranscriptional intranuclear
      event(s).

PMID- 7642727
TI  - [Treatment of pancreatic fistulas with somatostatin].
AB  - Four cases of pancreatic fistula were treated with somatostatin. Two cases
      occurred after caudal pancreatectomy and the other 2 after duodenopancreatectomy.
      Somatostatin rapidly reduced fistula flow by 50% 48 hours after treatment. The
      shorter hospital stay and reduced morbidity underline the importance of
      somatostatin in the treatment of pancreatic fistulae.

PMID- 7642728
TI  - [Morphology and biological integration of autodermoplasties in large incisional
      hernias. Results of an experimental study].
AB  - Their aim of the experimental study was to investigate the morphology and wound
      healing of "Kutisplastik"-technique, originally introduced by Loewe (1913) and
      Rehn (1914), from different conditions. We want to clarify the mechanism and
      development of revascularisation. RESULTS: The well known phases of wound healing
      also appear in the situation of a cutisplasty. In the exsudative reaction the
      cutis is covered from fibrin fibers. This leads to the development of granulation
      tissue. The cellular reaction demonstrates first the in-growth of capillary
      bundles and vessels in the collagen network of corium. The revascularisation is
      finished up to 14 days after the operation. The other part is the immigration of
      granulocytes and macrophages in the graft. The release of enzymes leads to the
      lysis of epidermal structures, cutaneous appendages and at least to collagen
      fibers of corium. There is also a proliferation from fibroblasts. The genesis
      from new collagen fibers is then observed so a scar tissue reveals. The
      "Kutisplastik"-technique contains that the epidermal side of the graft is turned
      upside-down towards the peritoneum and is sutured under as high tension as
      possible to the healthy fascia around. This morphology of healing is seen only
      under high-tension suturing. In the experimental mode of non-tension suturing
      there is a lack of success in cutisplasty for abdominal wall defects.

PMID- 7642729
TI  - [Leiomyosarcoma of the inferior vena cava. Apropos of a new case].
AB  - A leiomyosarcoma was diagnosed in the mid portion of the inter-renal inferior
      vena cava. Survival was long (6 years) but required 14 reoperations to remove
      metastases. During the first operation, vascular integrity was reestablished with
      a cava-cava prosthesis after exeresis of the upstream cava without removal of the
      left renal vein ostium. The right renal vein was sectioned and directly implanted
      onto the prosthesis. The pathology report confirmed the diagnosis of
      leiomyosarcoma with multiple metastases presenting cytonuclear anomalies which
      worsened with time.

PMID- 7642730
TI  - [Intercostal abdominal hernias. Apropos of 2 cases with right hernia].
AB  - Two patients presented with abdominal wall hernia in the 9th intercostal space on
      the right. Such localizations are extremely rare, occurring after closed or open
      chest or abdominal trauma producing two contiguous orifices in the diaphragm and
      the intercostal chest wall. The diaphragmatic orifice is due to a low lateral
      disinsertion and the intercostal orifice is situated in the 7th to 11th space,
      occurring immediately or later. Intercostal abdominal hernias are sometimes
      discovered due to pain or digestive or respiratory disorders. Clinical diagnosis
      is simple. CT scan confirms the clinical diagnosis and give a precise
      description. A direct or abdominal surgical approach is used to close the
      diaphragmatic orifice and the intercostal space with an unabsorbed suture. Muscle
      plasty or a unabsorbable prosthesis may be necessary. Early recurrence may occur
      if the orifice in the diaphragm is ignored.

PMID- 7642731
TI  - [French modification of the Bassini technic in a series of 1500 successfully
      treated cases of inguinal hernia in males over 25 years].
AB  - The high frequency of inguinal hernia leads to a major economic impact.
      Hospitalization duration and work loss time, post-operative pain, recurrences,
      risk of sepsis and complications directly related to prostheses are all factors
      which must be taken into account. We report our experience with the "French"
      modification of the classic Bassini technique. In our hands this technique
      involves: deep cure of the fascia transversalis, complete dissection of the
      inguinal canal, resection of the lateral oblique sac and the inner orifice of the
      inguinal canal, a off-loading incision in the right sheath to release tension.
      Recurrence rate under 1% after 10 years in type I and type II hernias according
      to the NYHUS classification led us to discuss the indications of prostheses
      which, in our opinion should be reserved for voluminous type II hernias and for
      bilateral or recurrent hernias.

PMID- 7642732
TI  - [Spontaneous rupture of the esophagus diagnosed late. Recovery by directed
      fistulization].
AB  - Spontaneous rupture of the oesophagus is uncommon and is difficult to diagnose in
      the early stage. Clinical signs are lacking or incomplete, causing a delay in
      diagnosis and therapy which requires both intensive medical care and surgery. The
      surgical procedure depends on the time lapse to diagnosis. We report a case
      diagnosed 16 days after rupture in which directed fistulization led to complete
      healing.

PMID- 7642733
TI  - [Post-laparoscopic incisional hernia. Apropos of a case].
AB  - Incisional hernia occurred in a patient after laparoscopic hysterectomy. The
      greater omentum was incarcerated in the tract of the suprapubic trocar (12 mm
      diameter). Diagnosis and treatment were performed during a second laparoscopy
      procedure. The greater number of trocar instruments and their larger diameter
      increases the risk of parietal morbidity after laparoscopic procedures. Elective
      closures of trocar incisions is recommended when exceeding 10 mm. Prevention of
      extra-umbilical incisional hernias and dehiscences appears to be more effective
      when suture is performed under laparoscopic vision with the trocar inserted. Both
      the aponevrosis and the peritoneal membrane should be treated.

PMID- 7642734
TI  - [Abscess of the rectovaginal wall in women. Apropos of a case].
AB  - Recto-vaginal septum abscess is a rare entity in women. The authors report a rare
      clinical observation of a recto-vaginal septum abscess in a 40 year old woman,
      hospitalized and treated in the Surgical Unit of the Yaounde General Hospital.
      Medical literature was reviewed and surgical indications discussed.

PMID- 7642735
TI  - [Foreign body in the rectum and its consequences. Apropos of 2 cases].
AB  - Two observations are reported, one due to a rectal wound developing into a life
      threatening situation due to late diagnosis after septic shock and cardiac
      arrest. In the second case, extraction of the foreign body was technically
      difficult.

PMID- 7642736
TI  - [Current aspects of surgery of the parathyroid glands].
AB  - Diagnosis and treatment of primary hyperparathyroidism has changed substantially
      during recent years. Routine serum calcium measurements and development of
      specific as well as sensitive PTH assays made primary hyperparathyroidism the
      most prevalent diagnosis of hypercalcaemia in the normal population. With
      increasing numbers of asymptomatic patients secondary complications are reduced
      but the demands made on surgeon's technical skill are much higher. In view of our
      experience in 329 patients with primary hyperparathyroidism during the last six
      years and a success rate of 98% we refrain from any localisation technique and
      advocate visualisation of all four glands.

PMID- 7642737
TI  - [Parietal abscess of lithiasic origin after laparoscopic cholecystectomy].

PMID- 7642738
TI  - [A case of hemorrhagic cyst of the urachus in adults].

PMID- 7642739
TI  - Enhanced tumor growth in brain dopamine-depleted mice following 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine (MPTP) treatment.
AB  - Brain dopamine influences immune functions and the role of immune functions in
      tumor growth is well established. Therefore, a study has been carried out to
      evaluate the correlation, if any, between brain dopamine and tumor growth. MPTP
      selectively destroys dopaminergic neurons in the brain. In the present study,
      Ehrlich carcinoma growth was evaluated in MPTP-treated mice. Results showed a
      correlation between depletion of striatal dopamine and enhanced tumor growth.
      Since in the present study striatal dopamine depletion in mice was associated
      with significantly decreased immune responses, the suggested correlation between
      brain dopamine and tumor growth was possibly mediated by the immune system.

PMID- 7642740
TI  - HIV-1 non-specifically stimulates production of transforming growth factor-beta 1
      transfer in primary astrocytes.
AB  - HIV-1 expression in monocytes/macrophages can be controlled by transforming
      growth factor-beta 1 (TGF-beta 1). TGF-beta 1 is present in astrocytes
      surrounding HIV-1-infected monocyte/macrophages in brain tissue from patients
      with AIDS but not from seronegative, normal individuals. We sought to determine
      whether or not production of TGF-beta 1 can be directly stimulated by HIV-1 in
      astrocytes. Astrocytes from neonatal rat cortex grown in primary culture were
      exposed to HIV-1 virions for 24 h. One day later, TGF-beta 1 was measured in
      culture supernatants by a biological assay. HIV-1 caused 1.7-2.1-fold increase in
      extracellular concentration of TGF-beta 1. TGF beta 1 production also was
      stimulated by recombinant HIV-1 proteins gp120, p66 and p24. Gp120 labeled with
      fluorescein was visualized inside astrocytes and its stimulatory effect was not
      blocked by antibodies against rat CD4. The effect was not specific to HIV-1 and
      its proteins, because non-opsonized Latex particles and leucine methyl ester
      (LME) (known to be phagocytosed and endocytosed, respectively, by astrocytes)
      also stimulated TGF-beta 1 production. The effect was inhibited by two inhibitors
      of the phago/endocytotic pathway, chloroquine and leupeptin. These results may be
      relevant to the neuropathogenesis of HIV-1 infection.

PMID- 7642741
TI  - Induction of anti-Purkinje cell antibodies in vivo by immunizing with a
      recombinant 52-kDa paraneoplastic cerebellar degeneration-associated protein.
AB  - We immunized five different strains of mice with the recombinant human PCD17
      protein, which is recognized by anti-Purkinje cell antibodies in the sera of
      patients with paraneoplastic cerebellar degeneration, and explored whether or not
      antibodies against cerebellar Purkinje cells could be induced in vivo.
      Autoantibodies against the cytoplasmic protein of Purkinje cells and other
      neurons were raised in all the strains of mice. These antisera stained the
      cytoplasm of cytoplasm of the Purkinje cell in a coarse, granular pattern, but
      spared the nucleus. The antisera did not stain cerebellar granular cells. This
      pattern of immunostaining seen with the mouse antisera is similar to that seen
      with the human PCD sera, but more widespread cells in the central nervous system
      were stained with these antisera. The titers of the induced antibodies were
      comparable to or even higher than those of humans. The deposition of IgG was also
      demonstrated in the cytoplasm of Purkinje cells in the immunized mice. In spite
      of the generation of anti-Purkinje cell antibodies in vivo, neither clinical nor
      pathological changes consistent with cerebellar degeneration were detected 1 year
      following the first immunization.

PMID- 7642742
TI  - Production and function of monocyte chemoattractant protein-1 and other beta
      chemokines in murine glial cells.
AB  - Monocyte chemoattractant protein-1 (MCP-1), formerly termed JE, is a member of
      the beta-chemokine (C-C chemokine) family and has been shown to be produced by a
      variety of cell types. Recently, mRNA of JE/MCP-1 was detected in astrocytes
      during the acute phase of experimental allergic encephalomyelitis (EAE). In
      addition, supernatants collected from human cultured astrocytes have recently
      been found to be chemotactic for monocytes. However, chemokine production and
      function in glial cells has not been fully examined. Using a sandwich ELISA
      assay, we have now quantitated MCP-1 levels and assessed MCP-1 function on murine
      glial cells. Lipopolysaccharide (LPS), interleukin (IL)-1 beta and tumor necrosis
      factor (TNF)-alpha induced MCP-1 secretion by astrocytes, but not microglia. In
      addition, pretreatment with interferon (IFN)-gamma significantly augmented MCP-1
      production by either LPS or the above cytokines. In contrast, LPS preferentially
      induced production of another beta-chemokine, macrophage inflammatory protein-1
      alpha (MIP-1 alpha) from microglial cells. MCP-1 induced chemotaxis of microglial
      cells and macrophages. Similarly, another beta-chemokine, TCA3, which is produced
      by encephalitogenic T lymphocytes, also induced chemotaxis of microglia and
      macrophages. These findings suggested that astrocytes and microglial cells
      differentially produce chemokines in the central nervous system, and that both
      astrocytes and T cells may facilitate recruitment and activation of microglial
      cells via production of beta-chemokines.

PMID- 7642743
TI  - Interleukin-1 and nerve growth factor induce hypersecretion and hypersulfation of
      neuroblastoma proteoglycans which bind beta-amyloid.
AB  - Inflammation and the response to injury may play an important role in the process
      of amyloidosis in Alzheimer's disease. We investigated the effect of interleukin
      1 (IL-1) and nerve growth factor (NGF) on the metabolism of neuroblastoma
      proteoglycans. IL-1 and NGF increased the net charge and the net secretion of
      neuroblastoma proteoglycans. NGF also specifically increased the relative amount
      of cell-associated and secreted heparan sulfate proteoglycans in these cells. We
      previously demonstrated that neuroblastoma heparan sulfate proteoglycan binds
      specifically to the amyloid beta-amyloid peptide involved in Alzheimer's disease.
      Heparan sulfate glycosaminoglycans synthesized by IL-1-stimulated cells
      demonstrated an increased relative binding affinity for the beta-amyloid peptide.
      Thus, IL-1 and NGF induce the hypersecretion and hypersulfation of neuroblastoma
      heparan sulfate proteoglycans which bind beta-amyloid. These studies link the
      process of inflammation and repair with alterations in the metabolism of heparan
      sulfate proteoglycans and amyloid formation in Alzheimer's disease and other
      disorders.

PMID- 7642744
TI  - Interleukin-10 (cytokine synthesis inhibitory factor) acts in the central nervous
      system of rats to reduce sleep.
AB  - Interleukin-10 (IL-10), originally designated a cytokine synthesis inhibitory
      factor, inhibits the synthesis of the pro-inflammatory cytokines IL-1 and tumor
      necrosis factor by stimulated human and mouse monocytes/macrophages; these
      cytokines are involved in the regulation of sleep. To determine if IL-10 reduces
      spontaneous sleep, we injected murine recombinant IL-10 intracerebroventricularly
      into rats prior to light onset. Non-rapid eye movements sleep was reduced. The
      behavioral responses to IL-10 were abolished by heat-inactivation of this
      cytokine. We believe these to be the first observations of central nervous system
      actions for this cytokine. These results further support the hypothesis that
      cytokines are involved in the regulation of sleep, and suggest an additional
      mechanism whereby sleep may be altered in response to an activated immune system.

PMID- 7642745
TI  - Changes in ACTH and beta-endorphin immunoreactivity in immune tissues during a
      chronic inflammatory stress are not correlated with changes in corticotropin
      releasing hormone and arginine vasopressin.
AB  - We have previously demonstrated that the chronic inflammatory stress of adjuvant
      induced arthritis in rats can alter levels of the neuropeptides
      adrenocorticotropin (ACTH), beta-endorphin, arginine vasopressin (AVP) and
      corticotropin-releasing hormone (CRH) in tissues of the immune system. We now
      present data showing that the patterns of these changes in the spleens and
      thymuses of Piebald-Viral-Glaxo rats are quite dissimilar throughout the course
      of the disease. Immunoreactive (ir)-CRH, AVP, ACTH and beta-endorphin were
      measured by radioimmunoassays in spleen and thymic extracts taken at days 3, 7,
      11 and 14 following injection of adjuvant. AVP was increased in the spleen at day
      14 compared to the controls (79.4 +/- 4.4 and 60.0 +/- 9.0 fmol/g tissue
      respectively), but no change occurred in the thymus. CRH contents were increased
      in the spleen at day 14 (33.4 +/- 3.5) compared to controls (22.1 +/- 2.4 fmol/g
      tissue), and in the thymus at day 11 (24.0 +/- 2.3) compared to controls (14.1 +/
      2.5 fmol/g tissue). Increases in ACTH content were observed in spleens from
      arthritic rats at days 3 (365 +/- 23), 11 (359 +/- 32) and 14 (355 +/- 45 fmol/g
      tissue) compared to controls (198 +/- 37 fmol/g tissue). In the thymus, however,
      ACTH was elevated only at day 14. Beta-Endorphin levels in the spleen were
      elevated only at day 14 (289 +/- 41) compared to controls (97 /+- 22 fmol/g
      tissue).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7642746
TI  - Enhancement of phagocytosis by dynorphin A in mouse peritoneal macrophages.
AB  - The effects of the opioid peptide dynorphin A (DynA) on phagocytosis in
      peritoneal macrophages was examined by flow cytometry (FCM). DynA enhanced
      phagocytosis in a dose-dependent manner. Leucine-enkephalin (Leu-Enk), methionine
      enkephalin (Met-Enk), beta-neo-endorphin (beta Neo-End), DynA(9-17) and DynA(13
      17) had no such activity. Alpha-Neo-endorphin (alpha Neo-End), dynorphin B
      (DynB), DynA(1-13) and DynA(6-17) enhanced phagocytosis less effectively than
      DynA. Naloxone did not inhibit the enhancement of phagocytosis induced by DynA.
      Unstimulated control phagocytosis was partially suppressed in Ca2+-free EGTA
      containing solution and even in this solution DynA enhanced phagocytosis.
      However, the enhancement by DynA was suppressed in EGTA- and BAPTA-AM-containing
      Ca2+-free solution. The present study showed that enhancement of phagocytosis by
      DynA was independent of extracellular Ca2+ ([Ca2+]o) and dependent on
      intracellular Ca2+ ([Ca2+]i). The present results support DynA being one of the
      mediators from the nervous system that modulates the immune system.

PMID- 7642747
TI  - Identification of m3, m4 and m5 subtypes of muscarinic receptor mRNA in human
      blood mononuclear cells.
AB  - In this study we made use of the Reverse transcription-polymerase chain reaction
      to analyze the expression of mRNA for the five subtypes of muscarinic
      acetylcholine receptors in human blood mononuclear cells. mRNA for m3, m4 and m5
      subtypes was detected, while mRNA for m1 and m2 muscarinic receptors was not
      found. Similar results were obtained for three different healthy human subjects
      studied. Interestingly, the m5 subtype was expressed at higher levels in blood
      mononuclear cells than in cerebral cortex. To our knowledge this is the first
      time that m5 muscarinic receptor mRNA has been found outside of the central
      nervous system.

PMID- 7642748
TI  - Production of nitrite by primary rat astrocytes in response to pneumococci.
AB  - Recent studies using a rat model of pneumococcal meningitis have shown that
      nitric oxide synthase (NOS) inhibitors greatly attenuated microvascular changes
      and brain edema formation. The site of NO production during bacterial meningitis
      is unknown. In this study we tested whether primary astrocyte cultures from
      neonatal rat cortex can be induced to release NO upon stimulation with
      pneumococci. NO production was assessed by measuring nitrite in the cell culture
      supernatant using the Griess reaction. Stimulation with heat-killed
      unencapsulated pneumococci (HKP) increased nitrite concentrations in astrocyte
      culture supernatants in a dose-dependent fashion. Administration of N-nitro-L
      arginine (L-NA), aminoguanidine, L-canavanine, cycloheximide, and dexamethasone
      prevented the increase in nitrite concentrations. Addition of L-arginine, but not
      of D-arginine, partially reversed the inhibitory effect of L-NA. Administration
      of SOD increased nitrite accumulation. Moreover, at 72 h after stimulation with
      heat-killed pneumococci (10(7) cfu/ml) astrocytes showed an inducible NOS-like
      immunoreactivity. Accumulation of nitrite was also observed when rat cerebellar
      neurons and microglia were stimulated with HKP, whereas there was only a slight
      increase of nitrite in media of rat C6 glioma cells, but no increase of nitrite
      when the human glioblastoma cell line LN-229 was stimulated with HKP. There was a
      stronger increase in nitrite levels when astrocytes from Lewis rats were used
      compared to that from Wistar rats. In conclusion, our study indicates that
      astrocytes, neurons and microglia are inducible for NO production upon
      stimulation with pneumococci.

PMID- 7642749
TI  - Interferon-beta downregulates interferon-gamma-induced class II MHC molecule
      expression and morphological changes in primary cultures of human brain
      microvessel endothelial cells.
AB  - Regulation of class II MHC (Ia) antigen expression by interferons beta and gamma
      was studied in an in vitro model of the blood-brain barrier. Primary cultures of
      human brain microvessel endothelial cells were incubated with IFN-beta, gamma or
      a combination of the two cytokines and surface expression of class II MHC
      molecules was investigated with the immunogold silver staining technique and
      enzyme-linked immunosorbent assay. Treatment of monolayers with IFN-beta (100
      6000 U/ml) failed to induce Class II MHC molecules. Co-incubation with IFN-gamma
      (100 U/ml), with or without pretreatment with IFN-beta, significantly inhibited
      the IFN-gamma-induced de novo expression in a concentration-dependent manner.
      Downregulation was less significant when incubation with both cytokines was
      preceded by 2-day treatment with IFN-gamma and was not observed in cultures
      incubated for an additional 4 days with IFN-gamma. Endothelial cells treated with
      IFN-gamma exhibited prominent morphological changes and frequent overlapping.
      These changes were not observed in the presence of either IFN-beta or both
      cytokines in the media. IFN-beta alone, or in combination with IFN-gamma,
      significantly inhibited the growth of endothelial cells, while only slight
      inhibition was observed with IFN-gamma. The results of these studies suggest that
      IFN-beta may function in modulating IFN-gamma-mediated immune responses in the
      human central nervous system at the level of the blood-brain barrier and this
      negative regulatory mechanism may be, at least in part, responsible for the
      recently reported beneficial effect of IFN-beta in relapsing-remitting multiple
      sclerosis.

PMID- 7642750
TI  - Human astrocyte growth regulation: interleukin-4 sensitivity and receptor
      expression.
AB  - We previously reported that interleukin-4 (IL-4) inhibited proliferation of a
      human astrocytic cell line derived from non-neoplastic adult cortex. To determine
      whether this effect was receptor-associated and/or limited to only non-neoplastic
      astrocytes, we examined IL-4 responsiveness and receptor expression in human
      astrocytic cell lines derived from three different sources: non-neoplastic
      cerebral cortex (lines P1N, P2N, W3N); neoplastic low grade astrocytoma (LGA)
      (lines FRLGA, RTLGA); and highly malignant glioblastoma multiforme (GBM) (lines
      STTG1, CRTG2, WITG3, RUTG4). All lines except RUTG4 GBM expressed IL-4 receptor
      mRNA. Proliferation and DNA synthesis were markedly suppressed by IL-4 in a dose-
      and time-dependent manner in all non-neoplastic astrocyte and LGA lines, but not
      (0/4) GBM. This negative growth-regulatory effect of IL-4 was blocked by specific
      antibody to human IL-4 receptor but not by irrelevant IgG. In contrast, IL-4
      stimulated interleukin-6 (IL-6) secretion in non-neoplastic astrocytes and LGA as
      well as in GBM cells expressing IL-4 receptor; secretion was undetectable in
      RUTG4 GBM which did not express receptor. These results indicate that: (i)
      responsiveness to IL-4 occurs in both non-neoplastic and neoplastic human
      astroglia; (ii) responsiveness is associated with IL-4 receptor expression; and
      (iii) sensitivity to negative growth signalling by IL-4 occurs selectively in
      astrocytes from non-neoplastic cortex or low grade neoplasia but not from highly
      malignant GBM.

PMID- 7642751
TI  - Expression of interleukin-3 and tumor necrosis factor-beta mRNAs in cultured
      microglia.
AB  - The function of interleukin-3 (or multi-CSF) in the hemopoietic system has been
      studied in great detail. Although its growth promoting activity on brain
      microglial cells has been confirmed both in vitro and in vivo, its presence in
      the brain and even in cultured brain cells has repeatedly been questioned. We
      have shown recently that isolated rat microglia express mRNA(IL-3) and synthesize
      IL-3 polypeptide. It is shown here by use of the PCR method, that mRNA(IL-3) is
      found also in C6 glioblastoma, in rat aggregate cultures, and in newborn and
      adult rat brain. Quantitation of amplified cDNA(IL-3) was achieved by non
      competitive RT-PCR using an elongated internal standard. IL-3 messenger RNA was
      almost undetectable in vivo and low in (serum-free) aggregate cultures. In
      isolated microglia, mRNA(IL-3) was increased upon treatment with LPS, PHA, with
      the cytokines IL-1 or TNF-alpha, with retinoic acid, dbcAMP or the phorbol ester
      TPA. Effects of LPS were inhibited by dexamethasone, while the glucocorticoid by
      itself had no effect on basal IL-3 expression. LPS increased mRNA(IL-3) in a
      concentration-dependent manner beginning with 10 pg/ml and reaching plateau
      levels at 10 ng/ml. LPS also increased mRNAs of TNF-alpha and TNF-beta. TNF-alpha
      mRNA was already detectable in untreated microglia and LPS-increased levels were
      sustained for a few days. In contrast, TNF-beta mRNA was observed only between 4
      and 16 h of LPS incubation. It was absent in LPS-free microglia, and after 24 h
      of LPS-treatment or later.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7642752
TI  - Soluble forms of intercellular adhesion molecule-1 (ICAM-1) block lymphocyte
      attachment to cerebral endothelial cells.
AB  - Serum levels of circulating ICAM-1 are increased in various disorders including
      inflammatory diseases of the central nervous system (CNS). We recently described
      an association between high sICAM-1 levels in the serum of patients with multiple
      sclerosis and disease activity. The functional consequences of increased
      circulating adhesion molecules are not fully understood. This may simply arise as
      a consequence of inflammation or may have immune modulating properties. ICAM-1
      plays an important role in the recruitment of activated lymphocytes to sites of
      inflammation within the CNS. We therefore tested the ability of soluble forms of
      ICAM-1 to prevent adhesion of activated lymphocytes to cerebral endothelial
      cells. Mitogen-activated blood mononuclear cells (PBMC) as well as PBMCs from
      patients with active multiple sclerosis adhered to cerebral endothelial cell
      cultures in vitro. This adhesion could be blocked if lymphocytes were
      preincubated with a recombinant form of soluble ICAM-1. In addition, serum from
      patients with active multiple sclerosis and high sICAM-1 levels blocked adhesion
      in a dose-dependent manner which was abrogated by pre-adsorption to an anti ICAM
      1 antibody. Since soluble forms of ICAM-1 are able to block lymphocyte adhesion
      to cerebral endothelial cells, they may provide new therapeutic tools to
      interfere with the pathogenesis of inflammatory diseases of the CNS.

PMID- 7642753
TI  - Temporal relationships and IL-2 dependency of prolactin-induced lymphocyte
      proliferation.
AB  - Recombinant preparations of human prolactin (hPRL) and interleukin 2 (hIL-2) as
      well as monoclonal antibodies to these growth factors were used to study the
      synergistic interaction of PRL and IL-2 in Nb2 rat lymphoma lactogen-dependent
      cells. It was shown that IL-2 stimulated Nb2 cell proliferation in lactogen-free
      culture medium. Experiments with short-term exposure to growth factor
      demonstrated that PRL was required only during the initial 12 h of incubation
      while IL-2 was mitogenic regardless of the time it was added. Antibody to IL-2
      partially inhibited both PRL- and IL-2-induced proliferation whereas antibody to
      PRL significantly decreased PRL but not IL-2-induced proliferation. These
      findings suggest that the complete mitogenic effect of PRL on Nb2 cells requires
      stimulation of IL-2 production.

PMID- 7642754
TI  - Interferon-beta downregulates expression of VLA-4 antigen and antagonizes
      interferon-gamma-induced expression of HLA-DQ on human peripheral blood
      monocytes.
AB  - We have studied the effect of recombinant human IFN-beta on the basal and IFN
      gamma-induced expression of adhesion molecules and class II MHC antigens on human
      peripheral blood monocytes and on ICAM-1 (intercellular adhesion molecule-1)
      expression of a human umbilical vein endothelial cell line (EAhy 926). We show
      that IFN-beta downregulates both basal and IFN-gamma-induced expression of VLA-4
      (very late activation antigen-4) antigen on monocytes, but has no effect on the
      expression of CD11a, CD11b, CD11c, L-selectin, CD18, ICAM-1, beta 1-integrin or
      CD44 on monocytes or ICAM-1 on EAhy 926 cells. We also show that IFN-beta
      antagonizes the IFN-gamma-induced expression of HLA-DQ-antigen, but not HLA-DR or
      HLA-DP antigens on monocyte surface. These findings may partially explain the
      beneficial effect of IFN-beta in multiple sclerosis, since VLA-4-antigen is
      critical for leukocyte recruitment into inflamed brain and downregulation of HLA
      class II expression diminishes antigen presenting capacity of monocytes.

PMID- 7642755
TI  - Effects of relaxation training on fear and arousal during in vivo exposure to a
      caged snake among DSM-III-R simple (snake) phobics.
AB  - Eight pairs of DSM-III-R snake phobic subjects (Ss) were exposed to a caged snake
      while seated in front of a package-conveyor apparatus during eight 4-minute
      trials. Heart rates and skin-conductance levels were recorded before and during
      each of the eight trials. Self-reports of fear were obtained after each trial.
      One S in each pair controlled the conveyor on alternating trials. One subject (S)
      in each pair had received a representative regimen of relaxation training
      beforehand. Heart-rate decreased more in Ss controlling the conveyor than in
      their yoked partners. Ss who had received relaxation training showed lower heart
      rate change, lower skin-conductance change, and lower self-reports of fear after
      the exposure trials. Relaxed Ss also moved the snake closer to themselves than
      did unrelaxed subjects on some trials.

PMID- 7642756
TI  - Prediction of outcome in behaviorally based insomnia treatments.
AB  - Factors related to successful behavioral intervention for individuals with
      insomnia are not well understood. In this study we employed the Neuroticism,
      Extraversion and Openness (NEO) Personality Inventory, to predict successful
      treatment outcome. Two behavioral treatments for insomnia, sleep restriction
      therapy (SRT) and relaxation training (RT) were employed in 32 elderly
      insomniacs. Following two baseline weeks, subjects underwent four weeks of
      individual treatment. Daily telephone call-ins generated data on sleep times and
      sleep latency. Follow-up occurred three months after the end of treatment.
      Results indicated that subjects showing the greatest improvement in total sleep
      time with both treatments were more traditional, conventional and rigid.
      Improvement in sleep onset latency was unrelated to NEO Scores. SRT appeared to
      be more effective for increasing total sleep time in these older subjects.

PMID- 7642757
TI  - Perceived functions of worry among generalized anxiety disorder subjects:
      distraction from more emotionally distressing topics?
AB  - Theories regarding worry have discussed both adaptive and maladaptive functions.
      The present study used rating scales of the six reasons for worry commonly
      reported by generalized anxiety disorder (GAD) clients to explore subjective
      perceptions of the functions of worry held by college student worriers meeting
      self-reported criteria for GAD and by control subjects. Subjects rated
      motivation, preparation for the worst, and avoidance/prevention of negative
      outcomes as the most typical reasons for their worry. However, the GAD group was
      discriminated from other comparison groups particularly by high ratings of
      "distraction from more emotional topics" as a reason for their worry.

PMID- 7642758
TI  - Fear of Spiders Questionnaire.
AB  - The Fear of Spiders Questionnaire (FSQ), an 18-item self-report questionnaire
      assessing spider phobia, was developed in an attempt to complement the
      information provided by the Spider Phobia Questionnaire (SPQ). Data obtained from
      338 undergraduates revealed that the FSQ was able to discriminate phobics from
      nonphobics, and indicated decrements in phobic responding from pretest to
      posttest following cognitive therapy. Test-retest data, obtained from non
      treatment control groups, indicated that scores on the FSQ are stable over a one
      month period. The FSQ also demonstrated adequate convergent validity due to its
      significant correlations with the SPQ and a behavioral avoidance test. Finally, a
      factor analysis revealed two factors accounting for 55% of the variance. It is
      argued that, compared to the SPQ, items on the FSQ are more explicit regarding
      the time period to be assessed, and may be more sensitive to differences between
      phobics and nonphobics and decrements in phobic responding following treatment.

PMID- 7642759
TI  - Treatment of a vocal tic by differential reinforcement.
AB  - The purpose of this study was to investigate the effectiveness of differential
      reinforcement of the absence of a chronic vocal tic in a 9-year-old male. This
      procedure was used after problems in the application of a simplified habit
      reversal procedure were encountered, and when it became evident that a
      reinforcement procedure was more acceptable to the patient. Once differential
      reinforcement was implemented, a substantial decrease (to near zero frequency) in
      coughing and throat clearing resulted. The reduction of coughing and throat
      clearing was seen within and outside the treatment session. Treatment effects
      were maintained after fading the reinforcement and throughout posttreatment (50
      weeks).

PMID- 7642760
TI  - A swallow induction avoidance procedure to establish eating.
AB  - Swallow induction has been used to shape swallowing behavior in dysphagic
      children and to accelerate swallowing in nondysphagic children with profound
      mental retardation who display primitive swallows. Swallow induction may be
      considered a type of prompt. This project coupled swallow induction with a
      modified delayed prompting paradigm to establish eating in a 3.5-year-old girl.
      Coupling these procedures produced prompt swallowing and established oral
      consumption. Follow-ups at 1, 2, 6 and 12 months demonstrated maintenance and
      further improvement of the newly acquired feeding skills. Implications for
      treatment and further research are discussed.

PMID- 7642761
TI  - Eye movement desensitization: three unusual cases.
AB  - Three complex cases are presented to document further the broad applicability of
      eye movement desensitization (EMD) for post traumatic stress disorder (PTSD). In
      the first subject this disorder was combined with panic attacks; in the second,
      sexual dysfunction was an additional consequence of childhood sexual abuse; and
      in the third the causative directly resulted in profound impairment of
      occupational and social function. In all three cases treatment produced rapid
      resolution of symptoms and functional recovery.

PMID- 7642762
TI  - Coprophagia as a manifestation of obsessive-compulsive disorder: a case report.
AB  - Coprophagia is seen, though uncommonly, in psychiatric hospitals among adult
      patients with diffuse brain disease and in individuals with subaverage
      intelligence. We describe here a case of coprophagia in an adult with normal
      cognitive functioning. Thorough assessment revealed that this coprophagia was a
      manifestation of obsessive-compulsive disorder. The problem behavior responded to
      a behavioral treatment program comprising exposure and response prevention.

PMID- 7642763
TI  - Social skills training in a depressed, visually impaired older adult.
AB  - A multiple baseline design was used to assess the effects of social skills
      training (SST) in a 65-year-old woman suffering from major depression and severe
      macular degeneration. Responses to role-played scenarios requiring assertiveness,
      in vivo request for assistance and social involvement, self-reported
      assertiveness, depression, and happiness were repeatedly recorded during
      baseline, treatment, and follow-up phases. Results showed progressive improvement
      in targeted social skills with SST in both clinic and home settings. Concurrent
      with enhanced levels of social skill were dramatic decreases of depression to a
      nonclinical level. Improved skill levels and diminished Geriatric Depression
      Scale scores were maintained during the 7-month follow-up period, except at the 6
      month assessment after which booster treatment was applied to reinstate maximum
      improvement.

PMID- 7642764
TI  - Identification of cues associated with compulsive, bulimic, and hair-pulling
      symptoms.
AB  - Subjects with obsessive compulsive disorder, bulimia nervosa, or trichotillomania
      selected cues which elicited or worsened their symptoms from a 339 item list.
      Principal components analysis suggested a four-component solution. Each disorder
      was significantly associated with one of these components. Diagnostic assignment
      based on component scores yielded 85% correct classification. The diagnostic
      groups did not differ on a negative feeling state component. The results indicate
      that both disorder-specific and generic components exist. This approach has
      potential for defining clinical subtypes, studying the interaction of feeling
      states and environmental cues in evoking symptoms, and designing treatment
      strategies.

PMID- 7642765
TI  - Evaluation of twin growth status at birth using individualized growth assessment:
      comparison with conventional methods.
AB  - OBJECTIVE: We sought to evaluate the growth status of twins at birth using
      individualized growth assessment methods and to compare this assessment with that
      obtained with conventional methods. STUDY DESIGN: Twenty twin pregnancies were
      studied longitudinally with ultrasound. Measurements of the head and abdominal
      cubes (A,B), head circumference (HC), abdominal circumference (AC), thigh
      circumference (ThC), and femur diaphysis length (FDL) made in the 2nd trimester
      were used to specify Rossavik growth models for each parameter in each fetus.
      These models were used to predict weight (WT), HC, AC, ThC, and crown-head length
      (CHL) at birth. Actual birth measurements made within 24 hours of delivery were
      compared to predicted values, the latter corrected using singleton [corrects for
      both technical problems (TP)] or twin [corrects for both technical problems (TP)
      and decreased soft-tissue deposition (DSTD)] correction factors where
      appropriate. Two sets of growth potential realization index (GPRI) values and
      their corresponding neonatal growth assessment scores (NGAS) were calculated and
      compared to previously established normal values. Birth measurements were
      compared with appropriate population age-specific size curves. These data were
      used to characterize and classify the growth status of each twin neonate.
      RESULTS: Individualized growth assessment identified five primary types of growth
      outcomes: normal (Group I, 45%); primarily DSTD (Group II, 22.5%); IUGR (Group
      III, 15%); above average soft-tissue deposition (Group IV, 5%); and growth
      acceleration (Group V, 7.5%). Within Group I was a subgroup with evidence of DSTD
      (Group Ib, 33.3% of Group I). Group II could be divided into two subgroups, one
      with only DSTD (Group IIa, 44.4% of Group II) and one with both DSTD and other
      growth abnormalities (Group IIb, 55.6% of Group II). Group III had multiple
      growth abnormalities which were more severe than those seen in Group II. All
      normal neonates were AGA and had virtually all anatomic parameters within their
      respective normal ranges. Of the neonates with definite evidence of IUGR (Groups
      IIb and III), only 4 of 11 (36.4%) were SGA and only 6 of 11 (54.5%) had any of
      the five anatomic parameters below their respective normal ranges. Only 1 of 3
      (33.3%) of neonates with growth acceleration was LGA and none (0%) of the five
      anatomic parameters were above their respective normal ranges. CONCLUSIONS:
      Individualized growth assessment methods provide a more comprehensive assessment
      of growth outcome in twins and detect a decrease in soft-tissue deposition not
      identifiable with conventional growth assessment procedures. The latter
      procedures are also less sensitive in the detection of both IUGR and growth
      acceleration.

PMID- 7642766
TI  - Causes of increasing width of right anterior extrarenal space seen in
      ultrasonographic examinations.
AB  - The right anterior extrarenal space is composed of the perirenal fascia, the
      right anterior perirenal space, the right anterior pararenal space, and the liver
      capsule. To clarify the probable causes of an increasing width of the right
      anterior extrarenal space, the width was measured using ultrasonography for a
      period of 8 months. The right anterior extrarenal space was measured 3 cm from
      the superior renal pole and the smallest width obtained in several different scan
      planes was used. In 1,114 ultrasound examinations, 35 patients were found to have
      an increased width of the right anterior extrarenal space. Among the 35 cases,
      the common probable causes for such a condition were found in 27 cases. Eight
      patients had hyperchogenicity in the right pararenal space, a condition
      considered to be due to an acute inflammation, including acute pancreatitis,
      acute cecal diverticulitis, acute appendicitis, ischemic bowel, acute
      cholangitis, liver abscess, and penetrated duodenal ulcer. Chronic inflammations
      of an adjacent organ, a previous history of laparotomy, a malignancy with
      peritoneal metastases, and treatment with corticosteroid were considered the
      causes behind the condition in the 19 patients with normal echogenicity. For the
      remaining 8 patients, causes were not found during the follow-up period. This
      study indicates that life-threatening diseases, such as acute or chronic
      inflammatory diseases and malignancy of the abdomen, could be the cause of an
      increase in the width of this space.

PMID- 7642767
TI  - Ultrasonic "honeycomb" appearance of uterine submucous fibroids undergoing cystic
      degeneration.
AB  - Uterine fibroids are the most common of uterine benign tumors. Generally, the
      ultrasonic appearance of uterine fibroids is typical, and diagnosis is
      uncomplicated. However, the sonographic characteristics of fibroids undergoing
      cystic degeneration, and especially those of the submucous type, may be
      misleading. We present a series of submucous fluids with cystic degeneration in
      peri- and postmenopausal women showing a distinct sonographic "honeycomb" pattern
      erroneously diagnosed as endometrial hyperplasia. The correct diagnosis was
      established by hysteroscopy.

PMID- 7642768
TI  - Relationship between portal blood flow measured by image-directed Doppler
      ultrasonography and hepatic blood flow measured by indocyanine green constant
      infusion in patients with cirrhosis.
AB  - The validity of portal blood flow measurement in image-directed Doppler
      ultrasound (PBF-IDU) is still under debate. In this study PBF-IDU has been
      compared with hepatic blood flow measured by the indocyanine green constant
      infusion technique (HBF-ICG), which is the reference invasive method with which
      to measure total hepatic blood flow in man (ie, the sum of hepatic artery and
      portal vein blood flow). In 27 cirrhotic patients with hepatopetal portal blood
      flow, PBF-IDU was measured by multiplying the portal vein cross-sectional area by
      the averaged mean velocity of blood in the vessel. About 1 hour later HBF-ICG was
      measured during hepatic vein catheterization performed to evaluate portal
      hypertension. In 19 of 27 patients, intrahepatic arterial resistance indices were
      also measured. PBF-IDU and HBF-ICG were 1.010 +/- 0.555 L/min (M +/- SD) and
      1.496 +/- 0.731 L/min, respectively. Blood flow measured by the two methods
      showed a close correlation (r = 0.80, p < 0.001). The regression line showed that
      HBF-ICG was systematically higher than PBF-IDU (mean difference +29 +/- 30%). The
      hepatic artery component of HBF-ICG probably accounted for the difference. An
      inverse correlation was found between the differences between the two procedures
      and intrahepatic arterial resistance indices (r = -0.52, p = 0.04), which may be
      considered indirect parameters of arterial supply. It can be concluded that image
      directed Doppler ultrasound is a sufficiently accurate method to measure portal
      blood flow in cirrhotics.

PMID- 7642769
TI  - Role of ultrasound in managing neuroblastoma detected by mass screening: a
      proposed ultrasonographic grading for children with neuroblastoma.
AB  - The ultrasonographic (US) findings of 25 infant cases detected by the Japanese
      mass screening program for neuroblastoma (NB) were reviewed. The following
      results were obtained: An identification of the primary site was possible in 96%
      of the cases with abdominal US. An estimation of the tumor weight was possible
      based on the mass volume, which was calculated from US measurements. With the
      combination of the estimated mass volume, local involvement, and distant
      metastasis, the US grading of NB was possible and closely corresponded to the
      surgical staging (84%). The NB cases of adrenal origin at U1a, with a mass volume
      of less than 16 mL, were all found to be stage I and presented the possibility
      for spontaneous regression.

PMID- 7642771
TI  - A case of Klatskin tumor with an unusual sonographic appearance.

PMID- 7642770
TI  - Triorchidism in the sibling of a patient with recently diagnosed seminoma.

PMID- 7642772
TI  - Gossypiboma: ultrasound-guided removal.

PMID- 7642773
TI  - Antenatal diagnosis of persistent right umbilical vein.

PMID- 7642774
TI  - Gallbladder tuberculosis: sonographic appearance.

PMID- 7642776
TI  - Prenatal ultrasonic findings of Wolffian duct cyst.

PMID- 7642775
TI  - Discordant umbilical artery flow velocity waveforms in spontaneous umbilical cord
      hematoma.

PMID- 7642777
TI  - The case for legalization of drugs.

PMID- 7642778
TI  - Operational issues in syringe exchanges: the New York City tagging alternative
      study.
AB  - It is estimated that 50% of the approximate 200,000 intravenous drug users (IDUs)
      in New York City (NYC) are infected with HIV. Syringe exchange, a common method
      of HIV prevention in many countries was legalized in NYC in 1992. As syringe
      exchange has gained public support and the number of functioning exchangers has
      grown in the country, more attention has been given to the study of operational
      characteristics of syringe exchanges. Syringe exchanges may be considered health
      service delivery organizations, and the specific methods of service delivery may
      greatly influence their effectiveness in reducing HIV risk behavior among
      injecting drug users. Improving operational characteristics of syringe exchanges
      requires both careful data collection, in order to reduce ambiguity in
      interpretation, and methods for cumulating knowledge, so that previous learning
      experiences need not be repeated with each new exchange. We report here on the
      practice of marking ("tagging") syringes distributed by exchanges in NYC during
      the period from 1990 through 1994. During this period the NYC exchanges operated
      illegally as underground exchanges, and then received legal status and expanded
      greatly. Developing regulations that reflect the reality of the program
      operations while allowing for monitoring and oversight is a complicated process,
      especially when implemented in states that maintain paraphernalia and
      prescription laws and where "unauthorized" possession of injection equipment
      remains a criminal activity under existing legal statutes. The particular
      situation in NYC which required the revision of existing regulations during a
      period of rapid program expansion and implementation of a large system of syringe
      exchange further illustrates the multiple pressures which accompany such a
      process. In order to implement meaningful regulations which maximize the public
      health benefits of syringe exchange programs on an individual and community
      level, recommendations are made.

PMID- 7642779
TI  - Protecting the weakest link: a proposal for universal, unblinded pediatric HIV
      testing, counselling and treatment.
AB  - This paper argues that a system of unblinded, universal testing, counseling and
      treatment for pediatric HIV should be implemented immediately in New York State.
      First, it argues that New York's health and social services bureaucracies, in
      conjunction with special interests that do not represent the interests of
      children, have resisted efforts to have infants tested and treated for HIV.
      Second, the paper suggests that the campaign against universal infant screening
      and treatment reflects our society's continuing, calculated decision to ignore
      the complexity of the HIV/AIDS epidemic. Third, the paper outlines a plan for a
      prompt and comprehensive system of HIV testing, counseling and treatment for
      infants and children, as well as for their parents and families, who are HIV
      positive. In the process of articulating the above positions, the paper documents
      the failure of universal blinded infant HIV screening in New York since 1987. It
      further explores the inadequacies of the proposed efforts by state and city
      regulatory authorities to improve the testing and counseling available for
      pediatric HIV. Although encouraged by New York State's recent move aggressively
      to test and treat HIV-positive infants and children in foster care, the paper
      argues that this effort must be expanded to apply to the entire newborn
      population. Finally, the paper examines in detail the limitations of testing and
      counseling provided to children in the foster care system.

PMID- 7642780
TI  - The case against mandatory newborn screening for HIV antibodies.
AB  - The paper examines the controversy surrounding legislative proposals in New York
      State that would require amending the public health law's stringent
      confidentiality provisions; the legislation calls for "unblinding" the results of
      a 7-year old statewide HIV seroprevalence study that tests newborns for HIV
      antibodies in order to track the incidence of HIV infection among parturient
      women. The pivotal point is made that mandatory disclosure of the test results is
      tantamount to mandatory testing of the mother, since presence (or absence) of HIV
      antibodies conclusively reveals the mother's HIV status. The author presents the
      history of the epidemiological study and documents the ongoing discussion of
      mandatory testing, within the medical, bioethical and public health community.
      Citing numerous papers, including the report of the Subcommittee on Newborn
      Screening of the New York State AIDS Advisory Council, the author--a member of
      both the council and its subcommittee--argues against the principle of mandatory
      testing in general and "unblinding" of the seroprevalence survey in particular.
      Besides making a strong argument from the ethical viewpoint, the paper provides
      ample medical data to support the argument that mandatory testing of newborns is
      poor public health policy that would be essentially ineffectual in the effort to
      stem the spread of HIV.

PMID- 7642781
TI  - Mandated life versus mandatory death: New York's disgraceful partner notification
      record.
AB  - In New York City in 1993, there were some 18,000 positive HIV tests but only 350
      partner notifications completed by the New York City Health Department. The bleak
      disparity between these two numbers should haunt us all. We will never know for
      certain how many lives could have been saved by universally available
      notification services, but looking at the results of current, obstructive New
      York State notification law and policy, we have to know we are facing an enormous
      public health failure. In states and cities with well-established notification
      programs, between 50 and 90% of HIV-positive clients cooperate voluntarily with
      notification and, typically, 90% of partners contacted seek HIV-testing and
      preventive counseling. There are no differences in cooperation based on race,
      gender or sexual orientation. In New York, urgently required reform means
      legislation to mandate that notification services are offered to all people who
      test positive and to require the state to supply enough trained personnel to
      undertake sensitive notification and counselling. With Black and Latina women-
      most of whom are mothers--now at the highest risk for sexual HIV infection, New
      York's refusal to undertake the life-saving policies common elsewhere has not
      only resulted in a horrible abandonment of a very vulnerable population, but also
      accelerated the orphaning of children at unprecedented rates.

PMID- 7642782
TI  - How I view the HIV epidemic as a Pentecostal.

PMID- 7642783
TI  - HIV in the inner cities: epidemiologic trends and their influence on policy
      making decisions.

PMID- 7642784
TI  - HIV/AIDS in the Czech Republic.

PMID- 7642785
TI  - The Czech Republic's national AIDS program.

PMID- 7642786
TI  - HIV/AIDS legislation in the Czech Republic.

PMID- 7642787
TI  - Regional AIDS center activities in the Czech Republic.

PMID- 7642788
TI  - Prophylaxis of opportunistic infections in HIV infection.

PMID- 7642789
TI  - Clinical manifestations of atypical mycobacterioses in the Czech Republic.

PMID- 7642790
TI  - The recent rise in prostitution in the Czech Republic.

PMID- 7642791
TI  - Increasing sexually transmitted disease rates among prostitutes in the Czech
      Republic.

PMID- 7642792
TI  - The development of epidemiology in Bohemia.

PMID- 7642793
TI  - History of the infectious disease clinic at the Bulovka Teaching Hospital.

PMID- 7642794
TI  - The different faces of the AIDS pandemic.

PMID- 7642795
TI  - Key policy debates on HIV in the inner city.

PMID- 7642796
TI  - HIV disease in the Czech Republic.

PMID- 7642797
TI  - Community planning: a national strategy to improve HIV prevention programs.
AB  - Beginning in fiscal year (FY) 1994, the Centers for Disease Control and
      Prevention (CDC), in collaboration with health departments and other human
      immunodeficiency virus (HIV) prevention partners, set in motion a significant
      innovation in HIV prevention programs: HIV Prevention Community Planning. This
      process, implemented by all 65 health departments receiving HIV prevention funds
      from CDC, requires that the identification and prioritization of HIV prevention
      needs to be a shared responsibility between the health departments administering
      the funds and representatives of the affected communities for whom the services
      are intended. Guidance for this planning process strongly embraces the notion
      that high priority HIV prevention strategies and interventions must have a sound
      basis in behavioral and social science and that program planning must begin with
      an accurate assessment of the epidemiology of the current and projected future
      HIV epidemic. Rather than mandate a single standardized process for all of the 65
      jurisdictions, CDC guidance provides flexibility for each jurisdiction to
      configure a planning process responsive to its own unique circumstances. However,
      all planning activities must be guided by 13 essential principles. This article
      will describe the principles and logistics of HIV Prevention Community Planning,
      identify the potential program benefits of this new undertaking, and describe
      implementation challenges.

PMID- 7642798
TI  - Morphological characterization of substance P receptor-immunoreactive neurons in
      the rat spinal cord and trigeminal nucleus caudalis.
AB  - Although there is considerable evidence that primary afferent-derived substance P
      contributes to the transmission of nociceptive messages at the spinal cord level,
      the population of neurons that expresses the substance P receptor, and thus are
      likely to respond to substance P, has not been completely characterized. To
      address this question, we used an antibody directed against the C-terminal
      portion of the rat substance P receptor to examine the cellular distribution of
      the receptor in spinal cord neurons. In a previous study, we reported that the
      substance P receptor decorates almost the entire dendritic and somatic surface of
      a subpopulation of spinal cord neurons. In the present study we have taken
      advantage of this labeling pattern to identify morphologically distinct
      subpopulations of substance P receptor-immunoreactive neurons throughout the
      rostral-caudal extent of the spinal cord. We observed a dense population of
      fusiform substance P receptor-immunoreactive neurons in lamina I at all segmental
      levels. Despite having the highest concentration of substance P terminals, the
      substantia gelatinosa (lamina II) contained almost no substance P receptor
      immunoreactive neurons. Several distinct populations of substance P receptor
      immunoreactive neurons were located in laminae III-V; many of these had a large,
      dorsally directed dendritic arbor that traversed the substantia gelatinosa to
      reach the marginal layer. Extensive labeling was also found in neurons of the
      intermediolateral cell column. In the ventral horn, we found that labeling was
      associated with clusters of motoneurons, notably those in Onuf's nucleus in the
      sacral spinal cord. Finally, we found no evidence that primary afferent fibers
      express the substance P receptor. These results indicate that relatively few, but
      morphologically distinct, subclasses of spinal cord neurons express the substance
      P receptor. The majority, but not all, of these neurons are located in regions
      that contain neurons that respond to noxious stimulation.

PMID- 7642799
TI  - Distribution of fine neurites of stomatogastric neurons of the crab Cancer
      borealis: evidence for a structured neuropil.
AB  - The neuropil of the stomatogastric ganglion of the crab Cancer borealis contains
      many neuronal processes that may be arranged either at random or in some form of
      orderly structure. In this study, we provide evidence for two types of order in
      the neuropil, a segregation of the processes based on their size and a cell
      specific distribution to the fine neurites. Identified neurons were injected with
      Lucifer yellow, fixed, and imaged as whole mounts with a confocal microscope.
      Four cell types were analyzed using the serial images, two pyloric neurons, one
      mixed pyloric/gastric neuron, and one gastric neuron. All of the neurons
      consisted of a approximately 60-microns-diameter soma, a approximately 20-microns
      diameter primary neurite projecting into the center of the neuropil, a number of
      < 10-microns-diameter medium-sized neurites radiating away from the center, and
      many < 3-microns-diameter fine neurites around the periphery of the neuropil. The
      neuropil can, therefore, be divided into three layers, a central core containing
      the largest neurites, an intermediate region containing both medium-sized and
      fine neurites, and a peripheral neuropil containing mostly fine neurites. The
      distribution of the fine neurites was mapped using a three-dimensional grid. We
      found that the fine neurites were distributed not at random within the neuropil
      but in consistent, cell-specific patterns.

PMID- 7642801
TI  - Molecular compartmentation expressed in cerebellar cultures in the absence of
      neuronal activity and neuron-glia interactions.
AB  - The purpose of the study was to determine if zebrin compartmentation developed in
      permanently isolated cerebellar cultures, in the presence of agents that block
      neuronal activity and in the absence of myelination and astrocytic ensheathment
      of Purkinje cells. Parasagittally oriented organotypic cultures derived from
      newborn mice and carefully undercut at explantation to exclude extracerebellar
      afferents were subjected to three conditions: 1) Some were maintained in standard
      nutrient medium; 2) some were chronically exposed to tetrodotoxin and elevated
      levels of magnesium to block neuronal activity; and 3) some were exposed to
      cytosine arabinoside for the first 5 days in vitro (DIV) to destroy granule cells
      and oligodendrocytes and functionally compromise astrocytes, so that the
      astrocytic survivors did not ensheath Purkinje cells. Cultures fixed as whole
      mount preparations were reacted with antibody to zebrin II. Cultures that were
      cryostat sectioned were dually reacted with antibody to zebrin II and calbindin.
      Groups of zebrin+ and zebrin- Purkinje cells were evident after 14 DIV in all of
      the experimental conditions, indicating that zebrin compartmentation developed 1)
      in isolated cerebellar explants, 2) in the absence of neuronal activity, and 3)
      in the absence of neuron-glia interactions such as myelination and glial
      ensheathment of Purkinje cell somata and dendrites. These results are consistent
      with the concept that expression of the zebrin+ and zebrin- phenotypes is an
      intrinsic property of Purkinje cells. The fact that zebrin expression seems to
      depend on an intrinsic program of differentiation in Purkinje cells suggests some
      role for zebrin compartmentation in cerebellar function.

PMID- 7642800
TI  - Expression of trk receptors in the developing and adult human central and
      peripheral nervous system.
AB  - A family of tyrosine receptor kinases known collectively as trk receptors plays
      an essential role in signal transduction mediated by nerve growth factor and
      related neurotrophins. To localize the major trk receptors (trkA, B and C) in the
      developing and adult central (CNS) and peripheral (PNS) nervous system, we
      generated monoclonal antibodies (MAbs) to extracellular (MAbs E7, E13, E16, E21,
      E29) and intracellular (MAb I2) domains of human trkA fused to glutathione S
      transferase. Several MAbs (E7, E13, E16) recognized glycosylated trkA (gp140trk
      and gp110trk) in Western blots, one MAb (E7) recognized non-glycosylated (p80trk)
      and glycosylated trkA in immunoprecipitation assays, and two MAbs (E13, E29)
      detected trkA on the cell surface of NIH3T3 cells transfected with a trkA cDNA.
      Although generated to trkA fusion proteins, this panel of MAbs also recognized
      trkB and trkC in flow cytometric studies of NIH3T3 cells transfected with trkB or
      trkC cDNAs. Thus, we used these pan-trk MAbs to probe selected regions of the CNS
      and PNS including the hippocampus, nucleus basalis of Meynert, cerebellum, spinal
      cord, and dorsal root ganglion (DRG) to localize trkA, B, and C receptors in the
      developing and adult human nervous system. These studies showed that trk
      receptors are expressed primarily by neurons and are detectable very early in the
      developing hippocampus, cerebellum, spinal cord, and DRG. Although the
      distribution and intensity of trk immunoreactivity changed with the progressive
      maturation of the CNS and PNS, immunoreactive trk receptors were detected in
      neurons of the adult human hippocampus, nucleus basalis of Meynert, cerebellum,
      spinal cord, and DRG. This first study of trk receptor proteins in the developing
      and adult human CNS and PNS documents the expression of these receptors in
      subsets of neurons throughout the developing and adult nervous system. Thus,
      although the expression of trk receptor proteins is developmentally regulated,
      the constitutive expression of these neurotrophin receptors by neurons in many
      regions of the adult human CNS and PNS implies that mature trk receptor-bearing
      neurons retain the ability to respond to neurotrophins long after terminal
      neuronal differentiation is complete.

PMID- 7642803
TI  - Postsynaptic gephyrin immunoreactivity exhibits a nearly one-to-one
      correspondence with gamma-aminobutyric acid-like immunogold-labeled synaptic
      inputs to sympathetic preganglionic neurons.
AB  - Peripheral regulation of cardiovascular function is fundamentally influenced by
      central excitation and inhibition of sympathetic preganglionic neurons in
      thoracic spinal cord. This electron microscopy study investigated whether the
      gamma-aminobutyric acid (GABA)-ergic and glycinergic inhibitory innervation of
      sympathetic preganglionic neurons arises from mutually exclusive afferent
      populations. Sympathetic preganglionic neurons were retrogradely labeled with
      cholera beta subunit. GABAergic terminals were identified using strict
      quantitative statistical analyses as those boutons containing significantly
      elevated levels of GABA-like immunogold labeling (GABA+). Glycinergic terminals
      were classified as those boutons opposite postsynaptic gephyrin immunostaining
      containing background levels of GABA-like immunogold labeling (gephyrin+/GABA-
      association). Approximately 43% of the synaptic terminals that contacted
      sympathetic preganglionic somata and proximal dendrites and that were opposite
      gephyrin were GABA-; the remaining 57% were GABA+. Only two GABA+ boutons (4%)
      that synapsed on identified sympathetic preganglionic neuron (SPN) processes were
      not opposite gephyrin immunostaining (GABA+/gephyrin- association). GABA
      /gephyrin+ associations were anticipated given prior anatomical, physiological,
      and pharmacological data. The observed nearly one-to-one correspondence between
      postsynaptic gephyrin immunoreactivity and GABA+ boutons was unexpected. Prior
      physiological and pharmacological experiments suggest that the postsynaptic
      effects of GABAergic inputs to sympathetic preganglionic neurons are mediated by
      activation of GABAA receptors. Those data, the present results, and other
      molecular, biochemical, and anatomical studies of gephyrin in the central nervous
      system (CNS) are consistent with two hypotheses: 1) Postsynaptic gephyrin is
      associated with GABAA receptors in the membranes of sympathetic preganglionic
      neurons, and 2) GABA+/gephyrin+ associations do not necessarily predict
      colocalization of GABA and glycine within single boutons synapsing on sympathetic
      preganglionic somata and dendrites.

PMID- 7642802
TI  - Autoradiographic localization of opioid receptors in vocal control regions of a
      male passerine bird (Junco hyemalis).
AB  - Previous studies have found opioid peptide-like immunoreactivity in avian vocal
      control regions, but whether these regions contain receptors for opioid peptides
      has not been examined. To address this question, we used quantitative in vitro
      autoradiography to determine the anatomical distribution and to measure the
      densities of mu, delta, and kappa opioid receptors in vocal control regions (area
      X, higher vocal center, and nucleus intercollicularis) of adult male dark-eyed
      juncos (Junco hyemalis). To evaluate whether opioid receptor densities in these
      regions depend on the activity of the reproductive system, we also measured these
      densities in birds collected during the spring, summer, and fall. We found area
      X, the higher vocal center, and nucleus intercollicularis to contain the three
      receptor types under study, but opioid receptor densities did not vary seasonally
      in any of these regions. The presence of specific opioid receptors in avian vocal
      control regions suggests the participation of opioids in the control of vocal
      behavior. This participation may consist of short-term (e.g., auditory
      processing) and/or long-term (e.g., neuronal plasticity) influences.

PMID- 7642804
TI  - The increase in B-50/GAP-43 in regenerating rat sciatic nerve occurs
      predominantly in unmyelinated axon shafts: a quantitative ultrastructural study.
AB  - The growth-associated protein B-50/GAP-43 is thought to play a crucial role in
      axonal growth. We investigated, by quantitative immunoelectron microscopy,
      whether there are differences in the subcellular distribution of B-50 in
      unmyelinated and myelinated axons of intact and regenerating sciatic nerves.
      Adult rats received an unilateral sciatic nerve crush and were euthanized 8 days
      later. Nerve pieces proximal from the crush site were embedded, and B-50 was
      visualized by specific B-50 antibodies and immunogold detection in ultrathin
      sections. The density of B-50 at the plasma membrane of unmyelinated axon shafts
      was significantly increased in the ipsilateral regenerating nerve in comparison
      to that of the contralateral intact nerve. In contrast, there was no significant
      difference in the B-50 density at the axolemma of myelinated regenerating and
      intact axon shafts. In the contralateral intact nerve, more B-50 was associated
      with the axolemma of unmyelinated axons than with the plasma membrane of
      myelinated axons. The density of axoplasmic B-50 was similar in intact
      unmyelinated and myelinated axon shafts, but was higher in regenerating nerve
      than in intact nerve. This suggests that enhanced axonal transport of B-50 occurs
      during axon outgrowth. Our study demonstrates a differential subcellular
      distribution of B-50 in unmyelinated and myelinated axon shafts in both the
      intact and regenerating sciatic nerve, indicating a differential inducible
      capacity for remodeling of the axon shafts.

PMID- 7642805
TI  - Distribution of Fos-like immunoreactivity in the caudal brainstem of the rat
      following noxious chemical stimulation of the temporomandibular joint.
AB  - Central expression of the protooncogene c-fos was used to examine areas receiving
      noxious sensory input from the rat temporomandibular joint (TMJ). Fos-like
      immunoreactivity (Fos-LI) in the caudal brainstem was visualized 2 hours after
      unilateral injection of the small-fiber-specific excitant/inflammatory irritant
      mustard oil into the TMJ region. Control animals received injection of either
      mustard oil into the subcutaneous fascia overlying the masseter muscle or mineral
      oil vehicle into the TMJ region. In all groups, Fos-LI was consistently observed
      ipsilaterally in the spinal trigeminal nucleus and cervical dorsal horn and,
      bilaterally, in the nucleus of the solitary tract and the ventrolateral medulla.
      The expression of Fos-LI ipsilaterally in the paratrigeminal nucleus was
      variable. Within the trigeminal sensory complex, Fos-LI was restricted to
      subnucleus caudalis and the caudal portions of subnucleus interpolaris near the
      level of the obex. Approximately 12% of Fos-LI cells in subnucleus caudalis and
      in the cervical dorsal horn were found in laminae III-VI. Compared to TMJ mustard
      oil injection, mineral oil injection produced less Fos-LI at all rostrocaudal
      levels, whereas subcutaneous mustard oil injection produced less Fos-LI in caudal
      subnucleus caudalis but similar amounts in the cervical dorsal horn. Neither of
      these injections yielded significant ipsilateral responses in subnucleus
      caudalis, indicating that Fos-LI in this region following TMJ mustard oil
      injection could be ascribed solely to small-fiber stimulation in the deep TMJ
      region. The wide rostrocaudal distribution of Fos-LI within the caudal brainstem
      reflects the distribution of TMJ-responsive nociceptive neurons that may underlie
      the spread and referral of pain from the TMJ region.

PMID- 7642806
TI  - Specificity of rabies virus as a transneuronal tracer of motor networks: transfer
      from hypoglossal motoneurons to connected second-order and higher order central
      nervous system cell groups.
AB  - The specificity of transneuronal transfer of rabies virus [challenge virus
      standard (CVS) strain] was evaluated in a well-characterized neuronal network,
      i.e., retrograde infection of hypoglossal motoneurons and transneuronal transfer
      to connected (second-order) brainstem neurons. The distribution of the virus in
      the central nervous system was studied immunohistochemically at sequential
      intervals after unilateral inoculation into the hypoglossal nerve. The extent of
      transneuronal transfer of rabies virus was strictly time dependent and was
      distinguished in five stages. At 1 day postinoculation, labelling involved only
      hypoglossal motoneurons (stage 1). Retrograde transneuronal transfer occurred
      from 2.0-2.5 days postinoculation (stage 2). In stages 2-4, different groups of
      second-order neurons were labelled sequentially, depending on the strength of
      their input to the hypoglossal nucleus. In stages 4 and 5, labelling extended to
      several cortical and subcortical cell groups, which can be regarded as higher
      order because they are known to control tongue movements and/or to provide input
      to hypoglossal-projecting cell groups. The pattern of transneuronal transfer of
      rabies virus resembles that of alpha-herpesviruses with regard to the
      nonsynchronous labelling of different groups of second-order neurons and the
      transfer to higher order neurons. In striking contrast to alpha-herpesviruses,
      the transneuronal transfer of rabies is not accompanied by neuronal degeneration.
      Moreover, local spread of rabies from infected neurons and axons to adjoining
      glial cells, neurons, or fibers of passage does not occur. The results show that
      rabies virus is a very efficient transneuronal tracer. Results also provide a new
      insight into the organization of cortical and subcortical higher order neurons
      that mediate descending control of tongue movements indirectly via hypoglossal
      projecting neurons.

PMID- 7642808
TI  - Correlation distance measurements of the female breast.
AB  - Ultrasonic waves propagating through soft tissue experience wavefront distortion.
      Adaptive wavefront compensation algorithms attempt to correct such distortion. A
      valuable design parameter is the isoplanatic patch size of the imaging medium.
      Its lateral extent is the FWHM of the correlation function. The range extent is
      defined similarly. The significance of the isoplanatic patch is that a new
      wavefront correction vector must be obtained whenever the ultrasound beam is
      moved a patch length. This paper reports measurements of wavefront correlation
      functions as well as statistics of the lateral correlation distance rho d (half
      the FWHM) within the female breast obtained from a population of 22 women (44
      breasts) and measured at 3 and 4 MHz with a large acoustic aperture (9.6 cm). A
      set of complex wavefronts radiated from single pointlike sources was measured
      from the opposing side of the breast. The propagation distance was 12 cm. rho d
      is the distance between two sources at which the correlation between their
      wavefronts drops to 0.5. The mean value at 3 MHz was found to be less than 1.5 mm
      for the premenopausal dense breast, 2.5 mm for the premenopausal fatty breast,
      and 2.0 mm for the postmenopausal breast. The mean value dropped by a factor of 2
      at 4 MHz for a group consisting of premenopausal fatty and postmenopausal
      breasts.

PMID- 7642807
TI  - Pathfinding by retinal ganglion cell axons: transplantation studies in
      genetically and surgically blind mice.
AB  - Optic axons show a highly stereotypical intracranial course to attain the visual
      centers of the brainstem. Here we examine the course followed by axons arising
      from embryonic retinae implanted in neonatal ocular retardation mutant mice in
      which there had been no prior innervation of the visual centers. Retinae placed
      on the ventrolateral brainstem adjacent to the normal site of the optic tract
      send axons dorsolaterally toward the ipsilateral superior colliculus, which they
      innervate along with a number of other subcortical visual centers. Somewhat
      unexpectedly, axons also course ventrally to cross at the level of the
      suprachiasmatic nucleus or, less frequently, caudal to the mammillary body to
      follow the route of the optic tract and innervate contralateral visual centers.
      Retinae implanted along the course of the internal capsule emit axons that follow
      projection fibers through the striatum to innervate the lateral geniculate
      nucleus and other optic nuclei. These grafts also appear to project to the
      lateral part of the ventrobasal nucleus of the thalamus. The results show that
      prior existence of an optic projection is not necessary for axons derived from
      ectopic retinae to attain visual nuclei, not only on the side of implantation but
      also on the contralateral side of the brain. The cues that these growing axons
      follow appear to be stable temporally. The fact that axons can also follow highly
      anomalous routes, such as through the internal capsule, to attain target nuclei
      in the brainstem suggests that the normal optic pathway is not an obligatory
      route for optic outgrowth.

PMID- 7642809
TI  - A test of the hypothesis that cavitation at the focal area of an extracorporeal
      shock wave lithotripter produces far ultraviolet and soft x-ray emissions.
AB  - Church hypothesized that the violent collapse of microbubbles in water in the
      focal area of an extra-corporeal shock wave lithotripter (ESWL) can generate
      biologically damaging far uv and soft x-ray photons. Two techniques were used to
      test this hypothesis. Gassy water (10 ml) was exposed to ten piezoelectric
      lithotripter shocks (P+ = 43 MPa, P- = 9 MPa). The resultant sonoluminescence was
      filtered by optical band-pass filters and measured using a photomultiplier tube
      (PMT). Next, a commercially available scintillation cocktail (Ecoscint A), which
      is formulated to convert high energy photons to visible light, was exposed to
      varying numbers of lithotripter shocks and the relative luminescence intensity
      measured and compared to background and distilled water luminescence readings.
      Results showed support for the hypothesized presence of near uv emissions
      (approximately 250 nm) and marginal support for the production of higher energy
      photons, possibly including far uv and soft x-ray emissions.

PMID- 7642810
TI  - Blue and fin whales observed on a seafloor array in the northeast pacific.
AB  - Calling blue and fin whales have been tracked using relative travel times and
      amplitudes from both direct and multipath arrivals to a seafloor array of
      seismometers. Calls of three fin whales swimming in the same general direction,
      but several kilometers apart, are believed to represent communication between the
      whales because of signature differences in call character, an alternating call
      pattern, and coordination of call and respiration times. Whale call tracks, call
      patterns, call character, and swimming speeds were examined during periods with
      and without the presence of noise. Noise sources included airguns, when the
      whales were subject to sound levels of up to 143 dB P-P (peak-to-peak) re: 1
      microPa over the 10 to 60-Hz band, and transits of merchant ships, when the
      whales received continuous levels up to 106 dB rms re: 1 microPa over the 10 to
      60-Hz band (115 dB P-P). Whale responses associated with these noises remain
      arguable.

PMID- 7642811
TI  - Sensory integration in the bottlenosed dolphin: immediate recognition of complex
      shapes across the senses of echolocation and vision.
AB  - In matching-to-sample tests, a bottlenosed dolphin (Tursiops truncatus) was found
      capable of immediately recognizing a variety of complexly shaped objects both
      within the senses of vision or echolocation and, also, across these two senses.
      The immediacy of recognition indicated that shape information registers directly
      in the dolphin's perception of objects through either vision or echolocation, and
      that these percepts are readily shared or integrated across the senses. Accuracy
      of intersensory recognition was nearly errorless regardless of whether the sample
      objects were presented to the echolocation sense and the alternatives to the
      visual sense (E-V matching) or the reverse, with samples presented to the visual
      sense and alternatives to the echolocation sense (V-E matching). Furthermore,
      during V-E matching, the dolphin was equally facile at recognition whether the
      sample objects exposed to vision were "live," presented in air in the real world,
      or were images displayed on a television screen placed behind an underwater
      window. Overall, the results suggested that what a dolphin "sees" through
      echolocation is functionally similar to what it sees through vision.

PMID- 7642812
TI  - Stimulus intensity and fundamental frequency effects on duplex perception.
AB  - Duplex perception occurs when part of the acoustic signal is used for both a
      speech and a nonspeech percept. This phenomenon has been interpreted as evidence
      of a distinct system for speech perception that precedes other specialized
      systems of general auditory processing (such as auditory grouping, and perception
      of pitch, loudness, and timbre). This interpretation was investigated by using an
      intensity-dependent form of duplex perception with the acoustic pair /da/ and
      /ga/. The "base" portion of the stimulus, common to both, consisted of the first
      and second formants and the steady-state portion of the third formant (F3). The
      F3 transition (either a sinusoid or a true formant), which cued the difference
      between /da/ and /ga/, was varied in intensity and fundamental frequency (F0).
      For every subject, the level at which each type of F3 transition was barely
      audible in the context of the base, i.e., duplex perception threshold, was first
      established. Next, identification functions were obtained by varying the
      intensity of the F3 transition relative to each subject's duplex perception
      threshold. Results revealed that duplex perception thresholds decreased as the F0
      of the F3 transition increasingly differed from the base. Also, identification
      functions showed that, as has been previously demonstrated, the F3 transition
      contributed to the speech percept over a wide range of intensities and
      fundamental frequencies. However, as F3 transition intensity increased well above
      duplex perception threshold, /ga/ identification decreased. Also, both /da/ and
      /ga/ identification progressively decreased as the F0 of the F3 transition
      increasingly differed from the base. Contrary to previous duplex perception
      reports, such findings indicate that both intensity and F0 information is
      available to the specialized speech perception system. Thus, the computations of
      the speech perception system and its relation to the general auditory processing
      systems need to be reexamined.

PMID- 7642813
TI  - Objective analysis versus subjective assessment of vowels pronounced by deaf and
      normal-hearing children.
AB  - Objective whole-spectrum and formant analyses have been performed on all 15 Dutch
      vowels pronounced in /C1VC2/ words by 24 deaf and 24 normal-hearing children, in
      order to develop a model of pronunciation quality for evaluating (deaf) speech;
      the results as obtained for adult males by Bakkum et al. [J. Acoust. Soc. Am. 94,
      1989-2004 (1993)] have been verified and extended. Spectral representations of
      the vowels were created by determining the output levels of a bank of 16 filters
      (90-7200 Hz), with 1/3-oct bandwidths and logarithmic spacing of their center
      frequencies. Spectral differences agree well with subjective differences in
      pronunciation quality obtained from magnitude estimation and identification
      experiments. Spectral differences not related to pronunciation quality judgments
      arise as a consequence of physiological interspeaker differences and variation in
      fundamental frequency, but these differences can be compensated for by speaker
      normalization and F0-compensation procedures. Using principal components analysis
      (PCA), the vowel spectra can be described by a limited number of dimensions,
      without losing much information; a description in a two-dimensional PCA subspace
      still agrees well with the subjective judgments and it also agrees with a
      description by the first two formants. The whole-spectrum approach provides a
      determinate, readily interpretable model of pronunciation quality for evaluating
      vowels. As a practical advantage, its computational requirements are modest and,
      in conjunction with PCA, the vowel dynamics can be visualized, which makes the
      approach suitable for vowel training and diagnostics.

PMID- 7642816
TI  - The minimum lung pressure to sustain vocal fold oscillation.
AB  - In previous experimental studies it has been observed that the minimum lung
      pressure to sustain vocal fold oscillation after its onset is lower than the
      threshold pressure needed to initiate it. This phenomenon is studied analytically
      using a previous body-cover model of the vocal folds and applying the describing
      function method to the general case of large amplitude oscillations. It is shown
      that the phenomenon is a consequence of the nonlinear characteristic of the
      effective aerodynamic damping introduced by the air pressure acting on the vocal
      folds. The results predict a value for minimum sustaining pressure equal to half
      the threshold pressure for a rectangular prephonatory glottis, which is in the
      order of experimental results.

PMID- 7642815
TI  - Listener adaptive characteristics of vowel devoicing in Japanese dialogue.
AB  - Listener adapative characteristics of Japanese vowel devoicing were investigated
      by analyzing (i) dialogues between professional teachers and hearing-impaired
      (HI) or normal-hearing (NH) children, and (ii) speech samples read by the
      teachers as fast and clearly as possible (RD). The teachers reduced the devoicing
      rate and lengthened the moras more in the HI vs NH samples, and even more in the
      HI vs RD samples. A logistic regression analysis of the devoicing rate suggests
      that the speech rate dependency of the devoicing rate is different among the HI,
      NH, and RD samples. When moras are lengthened, the predicted devoicing rate
      decreases more for the HI vs NH samples, and even more in the HI vs RD samples,
      suggesting that not only rate-dependent adjustments but also rate-independent
      adjustments significantly affect devoicing reduction. These results suggest the
      following: (1) Professional teachers of hearing-impaired children reduce their
      devoicing not only by lengthening the interval of successive voicing/devoicing
      gestures, but also by resizing component gestures to some extent, probably to
      improve the listener's comprehension; (2) vowel devoicing should be represented
      in terms of parameters of speech motor control; (3) it may be possible to develop
      an optimized communication method for hearing-impaired children by simulating
      such listener-adaptive adjustments in speech production.

PMID- 7642814
TI  - Effects of bandwidth on glottal airflow waveforms estimated by inverse filtering.
AB  - The aim of this research was to examine the effect of the bandwidth on parameters
      that are used to quantify glottal airflow waveforms that have been obtained by
      inverse filtering the acoustic signals. Three bandwidths (1, 2, and 4 kHz) were
      compared using /a/ vowels of different phonation types. Glottal waveforms were
      characterized using three ratios computed from the flow (open quotient, speed
      quotient, and closing quotient) and two parameters extracted from the
      differentiated flow (the amplitude of the negative peak and the return time from
      the negative peak to zero level). The results show that especially in pressed
      phonation the bandwidth should be at least 4 kHz. Distortion caused by an
      insufficient frequency range was most severe in the parameters extracted from the
      flow derivatives. Among the parameters computed from the flow signals, the
      closing quotient was affected most when the bandwidth was reduced.

PMID- 7642817
TI  - Perceptual separation of concurrent speech sounds: absence of across-frequency
      grouping by common interaural delay.
AB  - Three experiments and a computational model explored the role of within-channel
      and across-channel processes in the perceptual separation of competing, complex,
      broadband sounds which differed in their interaural phase spectra. In each
      experiment, two competing vowels, whose first and second formants were
      represented by two discrete bands of noise, were presented concurrently, for
      identification. Experiments 1 and 2 showed that listeners were able to identify
      the vowels accurately when each was presented to a different ear, but were unable
      to identify the vowels when they were presented with different interaural time
      delays (ITDs); i.e. listeners could not group the noisebands in different
      frequency regions with the same ITD and thereby separate them from bands in other
      frequency regions with a different ITD. Experiment 3 demonstrated that while
      listeners were unable to exploit a difference in interaural delay between the
      pairs of noisebands, listeners could identify a vowel defined by interaurally
      decorrelated noisebands when the other two noisebands were interaurally
      correlated. A computational model based upon that of Durlach [J. Acoust. Soc. Am.
      32, 1075-1076 (1960)] showed that the results of these and other experiments can
      be interpreted in terms of a within-channel mechanism, which is sensitive to
      interaural decorrelation. Thus the across-frequency integration which occurs in
      the lateralization of complex sounds may play little role in segregating
      concurrent sounds.

PMID- 7642818
TI  - Detecting signals of unexpected or uncertain durations.
AB  - Expectation of signal duration influences the signal detectability. This is
      demonstrated in two experiments in which percent correct was measured for both
      tonal and noise signals whose durations were either unexpected or uncertain. In
      both experiments, the signal at each duration was set to have a d' of about 1.5
      when that duration was presented alone and expected. When the six subjects were
      led to expect a short- or a long-duration signal using the probe-signal method,
      the detectability of signals decreased to near chance as the signal duration
      deviated from the expected value (experiment 1). When the subjects were led to
      expect a range of durations, the detectability was only slightly worse than when
      each signal was presented alone (experiment 2). Those results suggest that
      listeners adjust their temporal-integration intervals according to the demand of
      the specific task. Finally, the results obtained with the noise signal were
      analyzed using the multiple-look model and a modified energy-detector model.
      Assuming that the integration interval is matched to the expected signal
      duration, both models predict the detection of signals having unexpected
      durations reasonably well. Both models, however, fail to predict the small effect
      of duration uncertainty.

PMID- 7642819
TI  - Discrimination of changes in the spectral shape of two-tone complexes.
AB  - Discrimination experiments were performed for changes in the amplitude of two
      tone complexes. Thresholds were measured, among other things, as a function of
      bandwidth and center frequency. Usually, the overall intensity was roved in each
      and every presentation to prevent subjects from using loudness cues. The results
      show that changes in the spectral shape of broadband two-tone complexes can be
      perceived with and without a roving intensity level. For narrow-band signals,
      attempts have been made to explain the results in terms of the EWAIF model [Feth,
      Percept. Psychophys. 15, 375-378 (1974)]. This model could account for the data
      for signal bandwidths of 1 semitone or less. Modified EWAIF models did not yield
      better predictions. Thresholds for a change in the spectral shape were measured
      as a function of sensation level. The "near-miss" to Weber's law was not
      observed. This result is consistent with excitation pattern models.

PMID- 7642820
TI  - Effect of signal component phase on asynchrony discrimination.
AB  - The ability of listeners to detect the temporal asynchrony of a single harmonic
      in complex sounds was measured. The listeners discriminated an asynchronous
      complex from one in which all harmonics were synchronous (standard). The
      asynchrony was created either at the onset or offset of the complex. In the
      asynchronous complex, one component either began or ended after all other
      components in the complex, or it began or ended prior to all other components in
      the complex. The phase of the signal component was systematically varied in the
      range from 0 degrees to 180 degrees. All nonsignal components had the same sine
      phase. The results show that detecting the asynchrony at the onset is superior
      when all components are in sine phase. Altering the phase of the signal component
      increased thresholds by as much as a factor of 50, with the largest thresholds
      obtained when the signal component was inverted in phase. For offset conditions,
      the phase of the signal component had a much smaller and less consistent effect.
      Some of the observed effects of phase on the asynchrony thresholds can be
      understood by considering the response of the Roex filter [Patterson et al., J.
      Acoust. Soc. Am. 72, 1788-1803 (1982)] centered at the signal frequency.

PMID- 7642822
TI  - The role of frequency modulation in the perceptual segregation of concurrent
      vowels.
AB  - Two experiments investigated the effect of frequency modulation on the
      identification of vowel sounds presented concurrently with interfering vowels. In
      experiment 1, identification thresholds were measured for each of five target
      vowels, masked, in each trial, by one of ten masking vowels. Both target and
      masking vowels were synthesized using harmonically spaced frequency components.
      Inharmonic spacing was used in order to prevent powerful grouping processes which
      exploit fundamental frequency from dominating the results. The target vowels were
      synthesized with sinusoidal frequency modulation on each frequency component
      which was either coherent (same phase) or incoherent (random phases). The masking
      vowels were synthesized with components which were either modulated in the same
      way as the target vowel or were unmodulated. Identification thresholds were lower
      when the masking vowel had no modulation. The effect occurred for both coherent
      and incoherent frequency modulation, indicating that it is mediated by the
      movement of each component independently, rather than by grouping of coherently
      modulated components. This result is consistent in some respects with judgments
      of the prominence of competing vowels [S. E. McAdams, J. Acoust. Soc. Am. 85,
      2148-2159 (1989)], which show that modulated vowels are more prominent than
      unmodulated vowels regardless of the type of modulation applied to the competing
      vowels. Experiment 2 used a paradigm similar to that developed by McAdams, in
      order to compare more directly the effect of FM on vowel identification and vowel
      prominence. On each trial, three vowels were presented concurrently. Either none,
      one, or two of the vowels were modulated throughout, while modulation was applied
      to another vowel (the target) halfway through the stimulus. The vowels were
      either harmonic (with different fundamental frequencies) and coherently modulated
      or inharmonic and incoherently modulated. Accuracy of identification of the
      target vowel was not significantly different in the harmonic/coherent and
      inharmonic/incoherent conditions and declined, in each case, as the number of
      modulated background vowels increased. Overall, the results of experiments 1 and
      2, and of McAdams' prominence judgment data, suggest that there is an auditory
      mechanism for detecting frequency modulation which can alert the listener to the
      presence of frequency modulated sounds, but which is insensitive to across
      frequency differences in the pattern of that modulation.

PMID- 7642821
TI  - Reliability of pure-tone thresholds at high frequencies.
AB  - Standing waves, in the ear canal are created by the interference of two plane
      waves of the same frequency traveling in opposite directions. One manifestation
      of this phenomena is that any lateral motion of the transducer produces a change
      in the length of the canal and therefore, in general, a change in the sound level
      at the eardrum. Because of the smaller wavelength at the higher frequencies, the
      changes produced by movement of the transducer will be larger for the higher
      frequencies than for the lower frequencies. Thus, when the transducer is removed
      and replaced between successive threshold estimates, it is expected, from
      physical principles alone, that the intrasubject reliability of the estimates
      should be better at the lower frequencies. Previous studies, however, have shown
      that the intrasubject reliability of threshold estimates is nearly the same at
      both the low (0-8 kHz) and the high (8-16 kHz) frequency regions. A possible
      explanation for these anomalous results is proposed. While it is found that
      transducer placement increases the variability of threshold estimates more at the
      higher frequencies, it has also been found that conventional headphones reduce
      the size of the standing wave ratios compared with a hard wall termination. An
      additional factor is the steeper slope of the psychometric function at the higher
      frequencies. The combination of these factors produces a standard deviation for
      threshold estimates that is only about 1 dB larger at the high than at the low
      frequency region.

PMID- 7642823
TI  - Amplitude discrimination in masking release paradigms.
AB  - In the first phase of the study, detection thresholds were obtained in conditions
      that were associated with comodulation masking release (CMR), conditions that
      were associated with the masking-level difference (MLD), or conditions that were
      not associated with masking release (baseline conditions). In the second phase of
      the study, amplitude discrimination was determined for standard tones presented
      at sensation levels (SLs) 0-30 dB above the masked detection thresholds. Results
      indicated that, at matched SLs, amplitude discrimination was poorer under
      conditions of masking release than for baseline conditions, both for the MLD and
      for CMR. Implications of these results for models of masking release are
      discussed.

PMID- 7642824
TI  - Psychometric functions for level discrimination in cochlearly impaired and normal
      listeners with equivalent-threshold masking.
AB  - The purpose of this study was to determine whether the form of the psychometric
      functions for level discrimination (also known as intensity discrimination)
      measured in a two-interval, two-alternative forced-choice paradigm changes with
      hearing impairment. Measurements of sensitivity, d', as a function of delta L (=
      20 log[(p+delta p)lp], where p is pressure) were obtained in six listeners with
      cochlear impairments, five normal listeners tested in the quiet, and two masked
      normal listeners. Stimuli were chosen to encompass a wide range of conditions and
      difference limens. Results show that the d' is nearly proportional to delta L
      over the entire range of stimuli. This simple relationship is not changed by
      cochlear impairments or masking noise. These findings indicate that if the
      transformation from stimulus intensity to decision variable is affected by
      hearing impairment or masking, the change affects both the mean and the standard
      deviation in the same manner--i.e., the standard deviation may be proportional to
      the derivative of the transformation as was suggested by Zwislocki and Jordan [J.
      Acoust. Soc. Am. 79, 772-780 (1986)]. The results also lend support to the notion
      that delta L--plotted on a logarithmic scale--is an appropriate representation of
      level-discrimination performance.

PMID- 7642825
TI  - A spectral network model of pitch perception.
AB  - A model of pitch perception, called the spatial pitch network or SPINET model, is
      developed and analyzed. The model neurally instantiates ideas from the spectral
      pitch modeling literature and joins them to basic neural network signal
      processing designs to stimulate a broader range of perceptual pitch data than
      previous spectral models. The components of the model are interpreted as
      peripheral mechanical and neural processing stages, which are capable of being
      incorporated into a larger network architecture for separating multiple sound
      sources in the environment. The core of the new model transforms a spectral
      representation of an acoustic source into a spatial distribution of pitch
      strengths. The SPINET model uses a weighted "harmonic sieve" whereby the strength
      of activation of a given pitch depends upon a weighted sum of narrow regions
      around the harmonics of the nominal pitch value, and higher harmonics contribute
      less to a pitch than lower ones. Suitably chosen harmonic weighting functions
      enable computer simulations of pitch perception data involving mistuned
      components, shifted harmonics, and various types of continuous spectra including
      rippled noise. It is shown how the weighting functions produce the dominance
      region, how they lead to octave shifts of pitch in response to ambiguous stimuli,
      and how they lead to a pitch region in response to the octave-spaced Shepard tone
      complexes and Deutsch tritones without the use of attentional mechanisms to limit
      pitch choices. An on-center off-surround network in the model helps to produce
      noise suppression, partial masking, and edge pitch. Finally, it is shown how
      peripheral filtering and short-term energy measurements produce a model pitch
      estimate that is sensitive to certain component phase relationships.

PMID- 7642826
TI  - Grouping in pitch perception: evidence for sequential constraints.
AB  - Evidence is presented that sequential auditory grouping constraints apply to the
      perception of pitch. Experiment 1 shows that the pitch changes produced by
      mistuning the fourth harmonic of a 90-ms 12-harmonic 155-Hz fundamental complex
      tone are substantially reduced when the complex is preceded by four 90-ms tones
      at the same frequency as the mistuned component. Both the pitch changes and their
      reduction by the tonal sequence precursor remain when the mistuned component and
      the precursor are presented contralateral to the remaining components. Experiment
      2 shows that reducing the level of the same mistuned component reduces the size
      of the pitch change, but only if the mistuned component is presented
      ipsilaterally. To the extent that adaptation can be equated with a physical
      reduction in level, this result provides further evidence against peripheral
      adaptation playing a significant role in the auditory grouping of harmonics in
      pitch perception.

PMID- 7642827
TI  - Melody recognition and musical interval perception by deaf subjects stimulated
      with electrical pulse trains through single cochlear implant electrodes.
AB  - The perception of musical pitch was investigated in postlinguistically deaf
      subjects with cochlear implants. Stimuli consisted of sequences of biphasic
      electrical pulse trains at rates which represented the tones of the equal
      tempered musical scale, delivered at equalized comfortable loudness levels to
      selected single bipolar electrodes along the array of the Nucleus cochlear
      implant. Seventeen subjects correctly identified a mean of 44% of rhythmically
      intact familiar tunes, presented in an open-set paradigm. Three subjects were
      tested with a closed set of melodies without rhythmic cues. The results showed
      relatively higher recognition scores at lower pulse rates, although melody
      recognition remained possible up to rates of approximately 600-800 pulses per
      second. Stimulation of apical electrodes yielded higher recognition scores than
      of basal electrodes. The perception of musical intervals, defined as frequency
      ratios between two trains of stimulus pulse rates, was investigated in an
      interval intonation labeling experiment, for intervals ranging from a minor 3rd
      to a major 6th. Within a range of low pulse rates, subjects defined the intervals
      mediated by electrical pulse rate by the same ratios which govern musical
      intervals of tonal frequencies in normal-hearing listeners. It may be concluded
      that temporal cues are sufficient for the mediation of musical pitch, at least
      for the lower half of the range of fundamental frequencies commonly used in
      music.

PMID- 7642828
TI  - The "inverse problem" solved for a three-dimensional model of the cochlea. I.
      Analysis.
AB  - With nonactive cochlear models of the "classical" type, it is impossible to
      stimulate the characteristic type of frequency selectivity that is revealed by
      modern mechanical measurements of the motion of the basilar membrane (BM).
      Locally active models of the cochlea have been proposed to alleviate this problem
      but it remains uncertain whether the real cochlea is active in this sense. The
      present study was undertaken to investigate this subject in a more general and
      systematic way than has hitherto been done. The "inverse" problem is solved for a
      three-dimensional (3-D) model and a procedure is developed for recovering the BM
      impedance needed to stimulate the given BM response function. In the present
      paper the theoretical basis of the procedure is presented, and an analysis is
      given of the validity of the method and the errors involved. It is shown why the
      inverse problem is "ill-posed" and why the results of our procedure are more
      accurate in the region of the response peak than in the more basal region of the
      model. The latter finding serves to delimit the domain within which results of an
      inverse procedure (for instance, in the short- or long-wave approximation) are to
      be judged. In a subsequent paper the technique developed will be applied to
      actual data sets from the literature on mechanical BM measurements.

PMID- 7642829
TI  - The "inverse problem" solved for a three-dimensional model of the cochlea. II.
      Application to experimental data sets.
AB  - With "classical" nonactive models of the cochlea it is impossible to simulate the
      degree of frequency selectivity that is revealed by modern mechanical
      measurements of the motion of the basilar membrane (BM). Locally active models
      have been proposed to alleviate this problem, but it remains uncertain whether
      the actual cochlea is active in this sense. In the first paper of this series [E.
      de Boer, J. Acoust. Soc. Am. 98, 896-903 (1995)], the "inverse" problem is solved
      for a (classical) three-dimensional model and a procedure is developed for
      recovering the BM impedance needed to simulate a given BM response function. It
      was found that the results of this procedure will be more accurate in the region
      of the response peak than in the more basal region of the model. In the present
      paper the same procedure is applied to data of recent mechanical experiments. For
      the peak region the outcome is unequivocal: Recent measurement results can only
      be simulated by the classical model when it is made locally active. Resynthesis
      of the model response, on the basis of the recovered BM impedance, confirms the
      validity of the method in the peak region and strengthens this conclusion.

PMID- 7642830
TI  - Representation of a voice onset time continuum in primary auditory cortex of the
      cat.
AB  - The representation of voice onset time (VOT) for 197 single units in cat primary
      auditory cortex was studied for a /ba/-/pa/ continuum in which VOT was varied in
      5-ms steps from 0 to 70 ms. The effect of stimulus intensity, characteristic
      frequency of the neurons, and age of the animals was investigated. The minimum
      VOT represented in onset responses to both the voiceless and voiced parts of the
      sound (a "double-on" response) was dependent on overall stimulus level. An
      interaction was found between the efficacy of the burst in evoking neural
      activity and the size of the subsequent response to the onset of voicing. There
      was only a minor difference in the mean values for the minimal neural VOT for
      young (42 ms), juvenile (36 ms), and adult animals (46 ms), albeit that for
      individual young and juvenile animals more frequently values close to 10-15 ms
      were found. The cumulative distribution for the adult group showed a relative
      lack of neural VOTs around 30-40 ms. No other cues in the single unit and local
      neuronal group firing rate representation of VOT were found that were related to
      the categorical perception boundary.

PMID- 7642831
TI  - The development of frequency resolution in humans as revealed by the auditory
      brain-stem response recorded with notched-noise masking.
AB  - Studies of tuning in infants have reported that auditory brain-stem response
      (ABR) tuning curves generated using low-frequency probes are adultlike by 3
      months of age while high-frequency tuning curves remain immature [Folsom and
      Wynne, J. Acoust. Soc. Am. 81, 412-417 (1987)]. Behavioral studies have similarly
      reported adultlike low-frequency psychoacoustic tuning curves by 3 months with
      high-frequency tuning curves immature until approximately 6 months of age [L.
      Olsho, Infant Behav. Dev. 8, 371-384 (1985); Spetner and Olsho, Child Dev. 61,
      632-652 (1990); Schneider et al., J. Exp. Psych.: Human Percept. Perform. 16, 642
      652 (1990)]. Prior to this experiment, there have been no ABR studies of the
      development of frequency resolution for infants older than 3 months. In this
      study, notched-noise tuning functions were constructed from wave-V amplitude data
      for 3-month-old, 6-month-old, and adult subjects. Tone-pip stimuli at 1000, 4000,
      and 8000 Hz (50 dB nHL) were presented simultaneously with notched-noise masking
      centered at frequencies related to the tone-pip frequency (1/3-oct intervals
      above and below the probe frequency). By plotting wave-V amplitude across notched
      noise center frequency, isointensity tuning functions were generated for the
      three subject groups at the three probe frequencies. Auditory filter width (Q)
      and slope (dB/oct) were measured from each notched-noise tuning function in order
      to qualify degree of tuning. Consistent with previous studies, results showed
      that 3-month-old infants do not have adultlike tuning for high-frequency
      stimulation (8000 Hz). In contrast, by 6 months of age, tuning-function width (Q)
      is adultlike for both high- and low-frequency probes. These results, combined
      with previously reported evidence that the human cochlea is fully tuned at birth
      [Abdala et al., submitted to Hear. Res. (1995); Bargones and Burns, J. Acoust.
      Soc. Am. 83, 1809-1816 (1988)], suggest that immaturities in the auditory-neural
      system contribute to the broad high-frequency tuning consistently observed in 3
      month-old human infants.

PMID- 7642832
TI  - The implications of age of onset for delinquency risk. II: Longitudinal data.
AB  - The role of age of onset in the level of involvement in delinquent behavior as
      marked by seriousness and chronicity of involvement continues to draw extensive
      attention from researchers. This issue bears on some of the key causal
      contentions about the dynamism of involvement and the validity of a developmental
      model of antisocial behavior risk. Five waves of the National Youth Survey were
      utilized here to determine if, among a nationally representative sample, there
      was evidence of onset age influence on later involvement. Results suggest that
      early onset (before age 12) relates to higher rates of more serious acts over a
      longer period of time for boys and girls. Overall, the results suggest support
      for early onset spurring on later involvement, but the contribution is small once
      psychosocial predictors are considered. Onset age seems most important in
      understanding involvement in serious crime over several years. Involvement is
      explained best by peer variables for males and school and family variables for
      females. Onset age is explained by a wider range of variables than involvement
      and there is greater similarity of the psychosocial variables that explain onset
      for both genders. The interaction of involvement and predictors was noted,
      suggesting a dynamic model of risk. Implications for prediction and prevention
      are discussed.

PMID- 7642833
TI  - Early disruptive behavior, IQ, and later school achievement and delinquent
      behavior.
AB  - A series of structural equation model is developed to examine the relationship
      between early externalizing behaviors (conduct problems, attention deficit) and
      IQ measured at age 8 years, academic achievement over the period 10 to 13 years,
      and delinquent behavior to the age of 15 in a birth cohort of New Zealand
      children. These models indicated that early externalizing behaviors and IQ were
      related to later academic achievement and delinquent behavior by two quite
      distinct but highly correlated developmental sequences. In one sequence early
      conduct problems were predictive of later delinquency but were not directly
      related to later academic achievement. In the other sequence, attention deficit
      and IQ were prognostic of later school achievement but were not directly related
      to delinquency. Further, the apparent correlations between academic achievement
      and delinquency were adequately explained by the common and correlated effects of
      early behavior and IQ on later achievement and delinquency. These conclusions
      remained unchanged when the sample was stratified by gender, and when further
      explanatory factors were introduced into the model.

PMID- 7642834
TI  - The relationship between intelligence and vigilance in children at risk.
AB  - The purpose of this study was to compare two competing models as an explanation
      of the relationship between intelligence and sustained attention in educationally
      at-risk kindergarten children. One model assumes that lower-IQ subjects allocate
      greater amounts of attentional resource of information-processing tasks than
      higher-IQ subjects, whereas the other model assumes that a "less-than" optimal
      level of arousal is associated with decrements in task performance across time.
      Twenty-nine teacher-nominated at-risk and 29 normal achieving kindergarten
      students were administered the Wechsler Preschool and Primary Scale of
      Intelligence-Revised (WPPSI-R) and vigilance taks. Signal detection measures of
      stimulus detectability (d'), decision criterion (beta), correct detections, and
      false alarms were used to assess children's sustained attention across three time
      periods (2, 4, and 6 min). The important results were (a) high-risk children were
      inferior on d' measures when compared to normal achieving children, (b) vigilance
      measures did not vary over time in either group, and (c) intelligence and
      vigilance shared a common factor in high-risk, but not low-risk, children. The
      results suggest that children educationally at risk suffer deficits related to
      attentional capacity for processing information.

PMID- 7642835
TI  - A multisystems analysis of adolescent suicide attempters.
AB  - The present study tested an ecologically based model, which predicted that
      hopelessness (individual level) mediates the effects of family dysfunction
      (interpersonal level) and socioeconomic status (sociocultural level) on both
      suicidal intent and suicidal ideation, within a sample of attempters. Subjects
      included adolescent males and females presenting at a general hospital emergency
      room following suicide attempts. Baron and Kenny's (1986) criteria for testing
      mediation models through multiple-regression analyses were employed. Little
      evidence of mediation was found. Hopelessness proved to be the best predictor of
      suicidal intent and ideation within a sample of attempters.

PMID- 7642836
TI  - Methylphenidate and cognitive flexibility: dissociated dose effects in
      hyperactive children.
AB  - A randomized, double-blind, placebo-controlled trial was conducted to assess the
      acute effects of placebo and three doses of methylphenidate (MPH) (0.3, 0.6, 0.9
      mg/kg) on cognitive flexibility and overt behavior in 28 children with a
      confirmed diagnosis of attention deficit-hyperactivity disorder. Two underlying
      cognitive processes (response inhibition and response reengagement) were assessed
      by measuring the probability and speed with which subjects could inhibit
      responses to a primary task (forced-choice letter discrimination) and immediately
      execute a response to a secondary task (simple reaction time) when given a signal
      to do so. Results indicated that MPH enhanced cognitive flexibility, although the
      high dose was less effective than lower doses in enhancing response inhibition.
      Dissociations of dose effects on cognitive function and behavior were
      demonstrated: Dose-response functions for changes in behavior were linear,
      whereas the function for response inhibition was U-shaped. Findings argue against
      the typical clinical practice of determining the response to stimulant treatment
      from a single measure such as parent report of child behavior.

PMID- 7642837
TI  - Biased attention in childhood anxiety disorders: a preliminary study.
AB  - This study provides preliminary tests of two hypotheses: (1) Anxiety-disordered
      children show an attentional bias toward emotionally threatening stimuli, and (2)
      normal controls show an attentional bias away from emotionally threatening
      stimuli. Twelve children, 9 to 14 years of age, with primary diagnoses of anxiety
      disorder were compared with 12 normal controls matched for age, gender,
      vocabulary level, and reading ability. Subjects completed a reaction time task
      that measured visual attention toward threatening versus neutral words. The
      anxious group showed the predicted attentional bias toward threat words. However,
      controls did not show the predicted bias away from threat words. These results
      are the first showing that biased attentional processing occurs among clinically
      anxious children. The potential role of such an attentional bias in childhood
      anxiety disorders and future direction for research are discussed.

PMID- 7642838
TI  - Childhood conduct problems, attention deficit behaviors, and adolescent alcohol,
      tobacco, and illicit drug use.
AB  - The relationships between conduct problems and attention deficit behaviors at age
      8 years and the use of alcohol, tobacco, and illicit drugs at 15 years were
      studied in a birth cohort of over 900 New Zealand children. The analysis showed
      that while early conduct problems were significantly associated with later
      substance use there were no significant associations between early attention
      deficit behaviors and later substance use once the correlations between conduct
      problems and attention deficit behaviors were taken into account. These
      associations persisted after control for a range of potentially confounding
      covariates. Children who showed tendencies to conduct problems at age 8 consumed
      1.5 to 1.9 times more alcohol and had rates of alcohol-related problems, daily
      cigarette smoking, and illicit drug use that were 1.9 to 2.0 times higher than
      children with low conduct problem scores. It is concluded that attention deficit
      behaviors, in the absence of conduct problems, are not associated with later
      substance use. However, even when due allowance is made for social and contextual
      factors associated with both early conduct problems and later substance use,
      early conduct problems are a risk factor for later substance use.

PMID- 7642839
TI  - Is self-esteem an important outcome in hyperactive children?
AB  - Using a prospective design, this study examined (a) whether hyperactive children
      suffer from low self-esteem as adolescents; (b) whether low self-esteem is
      associated with poor functioning in adolescence; (c) whether hyperactive children
      exhibit a positive illusory bias, in which self-esteem is independent of level of
      functioning; and (d) whether self-esteem in adolescence is associated with poor
      functioning in adulthood. Subjects were 65 children diagnosed as hyperactive in
      childhood, and 62 matched controls sampled from a medical clinic. After
      controlling for current mental disorder, the hyperactive cohort reported lower
      self-esteem in adolescence, was judged by clinicians to have lower levels of
      overall adjustment in adolescence, and had lower educational achievement and
      occupational rank in adulthood, as compared to controls.

PMID- 7642840
TI  - Parent, teacher, and peer ratings of physically abused and nonmaltreated
      children's behavior.
AB  - Behavior ratings by parents, teachers, and classmates of physically abused fourth
      to sixth graders, identified from the New York City Maltreatment Register, and
      case-matched classroom controls, showed substantial concurrence among informants:
      Parents and teachers both rated significantly more behavioral disturbance in the
      abused children, and peers' ratings were significantly correlated with adults'
      ratings, especially those by teachers. Children's exposure to spouse or partner
      physical abuse, which had a substantial prevalence among both child-abusing and
      control families, reduced the difference in disturbance ratings between children
      who were themselves physically abused and those who were not. Overall, we
      conclude that physically abused children show pervasive behavioral disturbance,
      in that parents, teachers, and classmates all see higher levels of behavior
      problems and lower levels of socially desirable behavior in them compared to
      their nonmaltreated peers.

PMID- 7642841
TI  - Infant attachment security and maternal predictors of early behavior problems: a
      longitudinal study of low-income families.
AB  - In a longitudinal study of 100 low-income, mother-infant dyads, assessments of
      infant attachment security and maternal responsivity, involvement, depressive
      symptomatology, and perceived infant difficulty were used to predict later
      behavior problems at age 3. Attachment insecurity was related to behavior
      problems at age 3 when all insecure classifications were combined into one group
      and when insecurity was maintained at 12 and 18 months. For boys only, maternal
      depressive symptoms and low maternal involvement were associated with age 3
      behavior problems. For girls, perceived difficult temperament at ages 1 and 2
      were associated with later problem behavior.

PMID- 7642842
TI  - Interactional processes in families with disruptive boys: patterns of direct and
      indirect influence.
AB  - Patterns of direct and indirect influence were investigated in interactions among
      44 families with disruptive boys. Positive and negative behaviors were assessed
      for spouses and parent-child dyads, in different laboratory situations. For
      direct or reciprocal influence, positive behaviors in the father-child dyads were
      positively correlated; mothers' positive behaviors were positively correlated
      with boys' negative behaviors, suggesting an unexpected pattern of "inverse
      reciprocity." For indirect influences, the following associations were found:
      Fathers' negative behaviors toward their children predicted the children's
      negative behaviors toward their mothers, and mothers' negative behaviors toward
      their children predicted the children's negative behaviors toward their fathers,
      suggesting a form of setting event or displaced behavior pattern. The children's
      negative behaviors toward their mothers correlated with the fathers' behaviors
      toward the mothers, suggesting a modeling pattern. These indirect paths underline
      the relevance of taking into account family interlocked relationships when
      studying child disruptiveness.

PMID- 7642843
TI  - The stability of disruptive childhood behaviors.
AB  - The stability of child conduct and oppositional defiant behaviors during the
      period from 7 to 15 years was studied in a birth cohort of New Zealand children.
      These data were analyzed using two methods. In the first method the observed
      state to state changes in childhood behavioral tendencies were analyzed using
      empirical transition matrices. These results suggested that children classified
      as cases showed high rates of symptom remission, with approximately 50% of cases
      being classified as noncases 2 years later. In the second approach the data were
      analyzed using a latent Markov model which took account of errors of measurement
      in the classification of children. This analysis suggested the presence of strong
      continuities in childhood problem behaviors, with only 14% of children showing
      remission of behavioral problems within a 2-year period. The differences in the
      estimates yielded by the empirical transition matrices and the latent analyses
      were explained by the fact that there were relatively high probabilities that
      children who were cases were misclassified as a result of measurement errors.

PMID- 7642844
TI  - Distressed and nondistressed third- and sixth-grade children's self-reports of
      life events and impact and concordance with mothers.
AB  - This study examined the concordance of third- and sixth-grade distressed and
      nondistressed children's self-reports of the occurrence and perceived impact of
      life events that had occurred during the preceding 12 months with their mothers'
      perceptions. The study also examined whether maternal self-reports of dysphoria
      affects concordance between mother/child dyads on children's self-reports of
      occurrence and perceived impact of life events. Eighty-eight mother/child dyads,
      matched on Children's Depression Inventory scores, grade, sex, race, and school
      were included. Results indicated that distressed children endorsed more items on
      the Coddington Life Events Record (LER), and perceived them more negatively, than
      nondistressed children. Small, but statistically significant concordance rates
      were found between dyads on the occurrence of life events and the perceived
      impact of these events: Distressed children and their mothers had more mutually
      endorsed items than nondistressed children and mothers, and third-grade children
      had higher concordance rates with their mothers when compared to sixth-grade
      children. Third-grade children also appeared to commit more errors of commission
      on the LER. Finally, maternal distress mediated mother/child concordance.
      Possible explanations for these results and future research directions are
      discussed.

PMID- 7642845
TI  - Cardiologist versus internist management of patients with unstable angina:
      treatment patterns and outcomes.
AB  - OBJECTIVES: This study sought to assess the impact of generalist versus
      specialist direction on the pattern of care and outcome in patients admitted to
      the hospital for unstable angina. BACKGROUND: Physicians trained as internists or
      as cardiologists may have different approaches to treating patients with unstable
      angina. METHODS: We reviewed a prospectively collected cohort of patients
      discharged with a diagnosis-related group (DRG) diagnosis of unstable angina from
      William Beaumont Hospital, a large community-based hospital in southeast
      Michigan. Of 890 consecutive patients, 225 were treated by internists and 665 by
      cardiologists. We compared these two groups with respect to patterns of use of
      established pharmacotherapies for unstable angina, diagnostic testing and
      clinical outcome. RESULTS: Patients treated by internists less often had a
      previous cardiac history (53% vs. 80%, p < or = 0.0001). Internists were less
      likely to use aspirin (68% vs. 78%, p = 0.032), heparin (67% vs. 84%, p < or =
      0.001) or beta-adrenergic blocking agents (18% vs. 30%, p < or = 0.004) in their
      initial management. Exercise tests were performed more frequently by internist
      treated patients (37% vs. 22%, p < or = 0.001), but catheterization (27% vs. 61%,
      p < or = 0.0001) and angioplasty (7% vs. 40%, p < or = 0.0001) were utilized less
      frequently. The incidence of myocardial infarction was similar (11% vs. 9%) in
      the two groups, but the mortality rate tended to be higher (4.0% vs. 1.8%, p =
      0.06) in the internist group. CONCLUSIONS: Patients with unstable angina treated
      by internists were less likely to receive effective medical therapy or
      revascularization procedures and experienced a trend to poorer outcome. This
      study does not support a positive gatekeeper role for generalists in the
      treatment of unstable angina.

PMID- 7642846
TI  - Stabilizing the care of unstable angina.

PMID- 7642847
TI  - Asymptomatic Cardiac Ischemia Pilot (ACIP) study: impact of anti-ischemia therapy
      on 12-week rest electrocardiogram and exercise test outcomes. The ACIP
      Investigators.
AB  - OBJECTIVES: This report from the Asymptomatic Cardiac Ischemia Pilot (ACIP) study
      examines differences in the magnitude of reduction of myocardial ischemia as
      determined by exercise treadmill testing in patients randomized to three
      different treatment strategies: angina-guided medical therapy, ischemia-guided
      medical therapy and coronary revascularization. BACKGROUND: No prospective
      randomized clinical trials in patients with exercise electrocardiographic (ECG)
      abnormalities and asymptomatic cardiac ischemia on ambulatory ECG monitoring have
      compared the impact of different treatment strategies, including coronary
      revascularization, in terms of reducing myocardial ischemia. METHODS: The ACIP
      exercise protocol was used. Exercise variables measured included final exercise
      stage; presence of exercise-induced angina or ischemia; time to angina; time to 1
      mm ST segment depression; number of exercise ECG leads with abnormalities;
      maximal depth of ST segment depression in any lead; sum of ST segment depression;
      ST/HR index; and rate-pressure product at time to angina, at time to 1-mm ST
      segment depression and at peak exertion. RESULTS: Peak exercise time was
      increased by 0.5, 0.7 and 1.6 min in patients assigned to the angina-guided,
      ischemia-guided and coronary revascularization strategies, respectively, from the
      qualifying visit to the 12-week visit (p < 0.001). At the qualifying visit, the
      sum of exercise-induced ST segment depression was 9.4 +/- 5.0 (mean +/- SD), 9.6
      +/- 4.7 and 9.9 +/- 5.5 mm (p = NS) in the three treatment strategies,
      respectively. At the 12-week visit, the sum of exercise-induced ST segment
      depression was 7.4 +/- 5.7, 6.8 +/- 5.3 and 5.6 +/- 5.6 mm (p = 0.02) in the
      three treatment strategies, respectively. Each treatment strategy resulted in a
      significant reduction in all exercise-induced variables of myocardial ischemia
      measured at 12 weeks. CONCLUSIONS: Coronary revascularization significantly
      reduced the extent and frequency of exercise-induced myocardial ischemia compared
      with either medical strategy. The prognostic impact of these observations should
      be evaluated in a large-scale multicenter clinical trial.

PMID- 7642848
TI  - Asymptomatic Cardiac Ischemia Pilot (ACIP) study: outcome at 1 year for patients
      with asymptomatic cardiac ischemia randomized to medical therapy or
      revascularization. The ACIP Investigators.
AB  - OBJECTIVES: This report discusses the outcome at 1 year in patients in the
      Asymptomatic Cardiac Ischemia Pilot (ACIP) study. BACKGROUND: Comparative
      efficacy of medical therapy versus revascularization in treatment of asymptomatic
      ischemia is unknown. The ACIP study assessed the ability of three treatment
      strategies to suppress ambulatory electrocardiographic (ECG) ischemia to
      determine whether a large-scale trial studying the impact of these strategies on
      clinical outcomes was feasible. METHODS: Five hundred fifty-eight patients with
      coronary anatomy amenable to revascularization, at least one episode of
      asymptomatic ischemia on the 48-h ambulatory ECG and ischemia on treadmill
      exercise testing were randomized to one of three treatment strategies: 1)
      medication to suppress angina (angina-guided strategy, n = 183); 2) medication to
      suppress both angina and ambulatory ECG ischemia (ischemia-guided strategy, n =
      183); or 3) revascularization strategy (angioplasty or bypass surgery, n = 192).
      Medication was titrated atenolol-nifedipine or diltiazem-isosorbide dinitrate.
      RESULTS: The revascularization group received less medication and had less
      ischemia on serial ambulatory ECG recordings and exercise testing than those
      assigned to the medical strategies. The ischemia-guided group received more
      medication but had suppression of ischemia similar to the angina-guided group. At
      1 year, the mortality rate was 4.4% in the angina-guided group (8 of 183), 1.6%
      in the ischemia-guided group (3 of 183) and 0% in the revascularization group
      (overall, p = 0.004; angina-guided vs. revascularization, p = 0.003; other
      pairwise comparisons, p = NS). Frequency of myocardial infarction, unstable
      angina, stroke and congestive heart failure was not significantly different among
      the three strategies. The revascularization group had significantly fewer
      hospital admissions and nonprotocol revascularizations at 1 year. The incidence
      of death, myocardial infarction, nonprotocol revascularization or hospital
      admissions at 1 year was 32% with the angina-guided medical strategy, 31% with
      the ischemia-guided medical strategy and 18% with the revascularization strategy
      (p = 0.003). CONCLUSIONS: After 1 year, revascularization was superior to both
      angina-guided and ischemia-guided medical strategies in suppressing asymptomatic
      ischemia and was associated with better outcome. These findings require
      confirmation by a larger scale trial.

PMID- 7642849
TI  - Asymptomatic Cardiac Ischemia Pilot (ACIP) study: effects of coronary angioplasty
      and coronary artery bypass graft surgery on recurrent angina and ischemia. The
      ACIP investigators.
AB  - OBJECTIVES: The Asymptomatic Cardiac Ischemia Pilot (ACIP) study showed that
      revascularization is more effective than medical therapy in suppressing cardiac
      ischemia at 12 weeks. This report compares the relative efficacy of coronary
      angioplasty or coronary artery bypass graft surgery in suppressing ambulatory
      electrocardiographic (ECG) and treadmill exercise cardiac ischemia between 2 and
      3 months after revascularization in the ACIP study. BACKGROUND: Previous studies
      have shown that coronary angioplasty and bypass surgery relieve angina early
      after the procedure in a high proportion of selected patients. However,
      alleviation of ischemia on the ambulatory ECG and treadmill exercise test have
      not been adequately studied prospectively after revascularization. METHODS: In
      patients randomly assigned to revascularization in the ACIP study, the choice of
      coronary angioplasty or bypass surgery was made by the clinical unit staff and
      the patient. RESULTS: Patients assigned to bypass surgery (n = 78) had more
      severe coronary disease (p = 0.001) and more ischemic episodes (p = 0.01) at
      baseline than those assigned to angioplasty (n = 92). Ambulatory ECG ischemia was
      no longer present 8 weeks after revascularization (12 weeks after enrollment) in
      70% of the bypass surgery group versus 46% of the angioplasty group (p = 0.002).
      ST segment depression on the exercise ECG was no longer present in 46% of the
      bypass surgery group versus 23% of the angioplasty group (p = 0.005). Total
      exercise time in minutes on the treadmill exercise test increased by 2.4 min
      after bypass surgery and by 1.4 min after angioplasty (p = 0.02). Only 10% of the
      bypass surgery group versus 32% of the angioplasty group still reported angina in
      the 4 weeks before the 12-week visit (p = 0.001). CONCLUSIONS: Angina and
      ambulatory ECG ischemia are relieved in a high proportion of patients early after
      revascularization. However, ischemia can still be induced on the treadmill
      exercise test, albeit at higher levels of exercise, in many patients. Bypass
      surgery was superior to coronary angioplasty in suppressing cardiac ischemia
      despite the finding that patients who underwent bypass surgery had more severe
      coronary artery disease.

PMID- 7642850
TI  - Microvascular dysfunction in collateral-dependent myocardium.
AB  - OBJECTIVES: The aim of this study was to evaluate myocardial blood flow
      regulation in collateral-dependent myocardium of patients with coronary artery
      disease. BACKGROUND: Despite great clinical relevance, perfusion correlates of
      collateral circulation in humans have rarely been estimated by quantitative
      methods at rest and during stress. METHODS: Nineteen patients with angina and
      isolated occlusion of the left anterior descending (n = 14) or left circumflex (n
      = 5) coronary artery were evaluated. Using positron emission tomography and
      nitrogen-13 ammonia, we obtained flow measurements at baseline, during atrial
      pacing-induced tachycardia and after intravenous administration of dipyridamole
      (0.56 mg/kg body weight over 4 min). Flow values in collateral-dependent and
      remote areas were compared with values in 13 normal subjects. RESULTS: Flow at
      rest was similar in collateralized and remote myocardium (0.61 +/- 0.11 vs. 0.63
      +/- 0.17 ml/min per g, mean +/- 1 SD), and both values were lower than normal
      (1.00 +/- 0.20 ml/min per g, p < 0.01). During pacing, blood flow increased to
      0.83 +/- 0.25 and 1.11 +/- 0.39 ml/min per g in collateral-dependent and remote
      areas, respectively (p < 0.05 vs. baseline); both values were lower than normal
      (1.86 +/- 0.61 ml/min per g, p < 0.01). Dipyridamole induced a further increase
      in perfusion in remote areas (1.36 +/- 0.57 ml/min per g, p < 0.01 vs. pacing)
      but not in collateral-dependent regions (0.93 +/- 0.37 ml/min per g, p = NS vs.
      pacing); again, both values were lower (p < 0.01) than normal (3.46 +/- 0.78
      ml/min per g). Dipyridamole flow in collateral-dependent myocardium was slightly
      lower in patients with poorly developed than in those with well developed
      collateral channels (0.75 +/- 0.29 vs. 1.06 +/- 0.38 ml/min per g, respectively,
      p = 0.06); however, the former showed higher flow inhomogeneity
      (collateral/control flow ratio 0.58 +/- 0.10 vs. 0.81 +/- 0.22, respectively, p <
      0.02). A linear direct correlation was observed between flow reserve of
      collateral-dependent and remote regions (r = 0.83, p < 0.01). CONCLUSIONS:
      Despite rest hypoperfusion, collateral-dependent myocardium maintains a
      vasodilator reserve that is almost fully utilized during increases in oxygen
      consumption. A global microvascular disorder might hamper adaptation to chronic
      coronary occlusion.

PMID- 7642851
TI  - Coronary vasomotion during dynamic exercise: influence of intravenous and
      intracoronary nicardipine.
AB  - OBJECTIVES: Our aim was to evaluate the influence of a calcium channel blocking
      agent of the dihydropyridine group (nicardipine) on coronary vasomotion during
      dynamic exercise. BACKGROUND: Coronary vasomotion plays an important role in the
      pathophysiology of myocardial ischemia. METHODS: Twenty-nine patients with
      coronary artery disease were studied at rest and during bicycle exercise with the
      use of biplane quantitative coronary angiography. Twelve patients without
      pretreatment (group 1) served as control subjects. Seventeen patients (group 2)
      received nicardipine, either 0.2 mg by intracoronary injection (n = 9) or 2.5 mg
      intravenously (n = 8) before exercise. RESULTS: In the control group there was
      exercise-induced vasoconstriction (-29%, p < 0.001) of the stenotic segment but
      coronary vasodilation (+22%, p < 0.05) of the normal vessel segment. In group 2,
      nicardipine induced coronary vasodilation of both the normal (+16%, p < 0.001)
      and the stenotic vessel segment (+35%). During subsequent exercise there was some
      additional vasodilation of normal (+4%, p = NS) and stenotic arteries (+5%, p =
      NS). There was no difference between either intracoronary or intravenous
      nicardipine with regard to vasodilation. Application of sublingual nitroglycerin
      was associated with significant vasodilation of the normal vessel segment in
      groups 1 (+18%, p < 0.05) and 2 (+15%, p < 0.001). The stenotic vessels showed a
      significant increase in percent cross-sectional area after nitroglycerin in
      groups 1 (+12%, p = NS) and 2 (+51%, p < 0.001). Exertional angina pectoris
      occurred less frequently in group 2 (18%) than in group 1 (67% [p < 0.005 vs.
      group 2]); group 2 also had a smaller increase in mean pulmonary artery pressure
      (+14 vs. +21 mm Hg, p < 0.05). CONCLUSIONS: Exercise induces vasoconstriction of
      stenotic, but vasodilation of normal, coronary vessel segments. Intravenous and
      intracoronary nicardipine prevent vasoconstriction of stenotic coronary arteries
      during exercise and exert a significant anti-ischemic effect. The combination of
      two anti-ischemic drugs, nitroglycerin and nicardipine, has an additive effect on
      coronary vasomotion that is seen only in the stenotic vessel segment. Thus, the
      anti-ischemic action of nicardipine is mainly due to a primary effect on coronary
      vasomotor response rather than to secondary effects such as changes in loading
      conditions.

PMID- 7642852
TI  - Susceptibility of plasma low density lipoprotein to cupric ion-induced
      peroxidation in patients with variant angina.
AB  - OBJECTIVES: The purpose of this study was to investigate the peroxidative
      susceptibility of plasma low density lipoprotein in patients with active variant
      angina and to compare it with that in subjects without coronary spasm.
      BACKGROUND: Oxidized or modified low density lipoprotein can impair endothelium
      dependent vasoregulation and has atherogenic properties; it may be related to the
      genesis of coronary artery spasm by potentiating agonist-induced
      vasoconstriction. METHODS: The sensitivity of plasma low density lipoprotein for
      cupric ion (Cu2+)-induced peroxidation was examined. Low density lipoprotein was
      isolated from plasma in 112 patients: 21 with active variant angina, 18 with
      inactive variant angina without anginal attacks during the preceding 6 months, 39
      with significant organic coronary artery stenoses but without rest angina and 34
      control subjects without coronary artery disease. Lipid peroxidation products in
      low density lipoprotein were assayed as thiobarbituric acid-reactive substances
      before and after incubation with various concentrations of Cu2+ at 37 degrees C
      for 24 h. RESULTS: Significantly higher levels of generation of thiobarbituric
      acid-reactive substances from plasma low density lipoprotein after incubation
      with Cu2+ were seen in patients with active variant angina than in patients in
      the other three groups. The dose-response curve of low density lipoprotein
      peroxidation induced by Cu2+ shifted to the left in this group as compared with
      the curve in the other three groups. The vitamin E (alphatocopherol) content of
      low density lipoprotein fraction in these patients was significantly lower than
      that in the other groups. After > or = 6 months of an angina-free period in five
      patients with active variant angina, thiobarbituric acid-reactive substances
      induced by 0.5 mumol/liter Cu2+ in low density lipoprotein were significantly
      decreased and vitamin E content was significantly increased. CONCLUSIONS: These
      results indicate that vitamin E-deficient plasma low density lipoprotein in
      patients with active variant angina is highly susceptible to peroxidative
      modification.

PMID- 7642853
TI  - Incremental value of prognostic testing in patients with known or suspected
      ischemic heart disease: a basis for optimal utilization of exercise technetium
      99m sestamibi myocardial perfusion single-photon emission computed tomography.
AB  - OBJECTIVES: This study assessed the incremental prognostic implications of normal
      and equivocal exercise technetium-99m (Tc-99m) sestamibi single-photon emission
      computed tomography (SPECT) and sought to determine its incremental prognostic
      value, impact on patient management and cost implications. BACKGROUND: The
      prognostic implications of Tc-99m sestamibi SPECT are not well defined, and risk
      stratification using this test has not been explored. METHODS: We studied 1,702
      patients referred for exercise Tc-99m sestamibi SPECT who were followed up for a
      mean (+/- SD) of 20 +/- 5 months. Patients with previous percutaneous
      transluminal coronary angioplasty or coronary artery bypass surgery were
      excluded. The SPECT studies were assessed using semiquantitative visual analysis.
      Cardiac death and myocardial infarction were considered "hard" events, and
      coronary angioplasty and bypass surgery > 60 days after testing were considered
      "soft" events. RESULTS: Of the 1,702 patients studied, 1,131 had normal or
      equivocal scan results. A total of 10 events occurred in this group (1 cardiac
      death and 1 myocardial infarction [0.2% hard events]; 4 coronary angioplasty and
      4 bypass surgery procedures [0.7% soft events]). The rates of hard events and
      referral to catheterization after SPECT were similarly low in patients with a low
      (< 0.15), intermediate (0.15 to 0.85) and high (> 0.85) post-exercise treadmill
      test (ETT) likelihood of coronary artery disease. With respect to scan type,
      patients with normal, probably normal or equivocal scan results had similarly low
      hard event rates. In the 571 patients with abnormal scan results, there were 43
      hard events (7.5%) and 42 soft events (7.4%) (p < 0.001 vs. 1,131 patients with
      normal scan results for both). When the complete spectrum of scan responses was
      considered, SPECT provided incremental prognostic value in all patient subgroups
      analyzed. However, the nuclear scan was cost-effective only in patients with
      interpretable exercise ECG responses and an intermediate to high post-ETT
      likelihood of coronary artery disease and in those with uninterpretable exercise
      ECG responses and an intermediate to high pre-ETT likelihood of coronary artery
      disease. CONCLUSIONS: Normal or equivocal exercise Tc-99m sestamibi study results
      are associated with a benign prognosis, even in patients with a high likelihood
      of coronary artery disease. Although incremental prognostic value is added by
      nuclear testing in all patient subgroups, a testing strategy incorporating
      nuclear testing proved to be cost-effective only in the groups with an
      intermediate to high likelihood of coronary artery disease before scanning.

PMID- 7642855
TI  - Myocardial infarction in young adults: angiographic characterization, risk
      factors and prognosis (Coronary Artery Surgery Study Registry).
AB  - OBJECTIVES: This study examined the angiographic characteristics, coronary risk
      factors and prognosis in young men and women with a history of myocardial
      infarction compared with that in older patients. BACKGROUND: There are few data
      regarding myocardial infarction in young adults. It is undetermined whether the
      development of myocardial infarction at a young age represents a form of coronary
      heart disease with an adverse prognosis. METHODS: Of the 8,839 patients with a
      history of myocardial infarction in the Coronary Artery Surgery Study (CASS),
      there were 294 men < or = 35 years old and 210 women < or = 45 years old.
      Coronary anatomy, baseline characteristics and prognosis were compared in younger
      and older patients. RESULTS: Young men and women more often had angiographically
      normal coronary arteries, nonobstructive disease < 70% stenosis and single-vessel
      disease than older patients (p < 0.0001). Current smoking was more frequent in
      young patients (p < 0.0001). Hypertension and diabetes were more frequent in both
      older men and women, whereas a positive family history of premature coronary
      disease was significantly more prevalent only in young men. The survival rate at
      7 years was improved for young men compared with that in older men (84% vs. 75%,
      p = 0.0094) and for young women compared with that in older women (90% vs. 77%, p
      = 0.0004). When multivariate analysis was applied to the data, the survival
      advantage for young patients remained after adjustment. CONCLUSIONS: Young
      patients with a myocardial infarction have a favorable prognosis compared with
      that in older patients.

PMID- 7642854
TI  - Improved cardiac risk stratification in major vascular surgery with dobutamine
      atropine stress echocardiography.
AB  - OBJECTIVES: This study sought to optimize preoperative cardiac risk
      stratification in a large group of consecutive candidates for vascular surgery by
      combining clinical risk assessment and semiquantitative dobutamine-atropine
      stress echocardiography. BACKGROUND: Dobutamine-atropine stress echocardiography
      has been used for the prediction of perioperative cardiac risk in a small group
      of patients scheduled for elective major vascular surgery on the basis of the
      presence or absence of stress-induced regional left ventricular wall motion
      abnormalities. METHODS: Clinical risk assessment and dobutamine-atropine stress
      echocardiography were performed in 302 consecutive patients presenting for major
      vascular surgery. The extent and severity of stress wall motion abnormalities and
      the heart rate at which they occurred, in addition to the presence of wall motion
      abnormalities at rest, were assessed. RESULTS: The absence of clinical risk
      factors (angina, diabetes, Q waves on the electrocardiogram, symptomatic
      ventricular tachyarrhythmias, age > 70 years) identified a low risk group of 100
      patients with a 1% cardiac event rate (unstable angina). Dobutamine-atropine
      stress echocardiographic findings were positive in 72 patients. Twenty-seven
      patients had a perioperative cardiac event (cardiac death in 5, nonfatal
      infarction in 12, unstable angina pectoris in 10); all 27 patients had positive
      stress test results (positive predictive value 38%, negative predictive value
      100%). The semiquantitative assessment of the extent and severity of ischemia did
      not provide additional prognostic information in patients with positive test
      results. In contrast, the heart rate at which ischemia occurred defined a high
      risk group with a low ischemic threshold (38 patients with 20 events [53%]) and
      an intermediate risk group with a high ischemic threshold (34 patients with 7
      events [21%]). All 5 patients with a fatal outcome and 8 of 12 with a nonfatal
      myocardial infarction were in the high risk group with a low ischemic threshold.
      CONCLUSIONS: Clinical variables identify 33% of patients at very low risk for
      perioperative complications of vascular surgery in whom further testing is
      redundant. In all other candidates, dobutamine-atropine stress echocardiography
      is a powerful tool that identifies those patients at intermediate risk and a
      small group at very high risk. Risk stratification with a combination of clinical
      assessment and pharmacologic stress echocardiography has the potential to
      facilitate clinical decision making and conserve resources.

PMID- 7642856
TI  - Early spontaneous intermittent myocardial reperfusion during acute myocardial
      infarction is associated with augmented thrombogenic activity and less myocardial
      damage.
AB  - OBJECTIVES: This study investigated the influence of early spontaneous
      intermittent reperfusion on the extent of myocardial damage and its relation to
      endogenous hemostatic activity. BACKGROUND: In the early phase of acute
      myocardial infarction coronary occlusion is often intermittent, even before
      thrombolytic therapy is administered. The relation between this phenomenon,
      myocardial damage and hemostatic activity is unknown. METHODS: Holter ST segment
      recording and pretreatment plasma tissue-type plasminogen activator (t-PA)
      antigen, plasminogen activator inhibitor-1 (PAI-1) antigen, prothrombin fragment
      F1 + 2 and soluble fibrin levels were measured in 57 patients with acute evolving
      myocardial infarction. Spontaneous intermittent myocardial reperfusion, defined
      as two or more episodes of transient resolution of ST segment elevation to within
      0.05 mV of baseline, lasting > or = 1 min, before the start of recombinant t-PA
      (rt-PA) treatment was present in 28 patients (group 1) and absent in 29 (group
      2). Left ventriculography and coronary angiography were performed 90 min after
      intravenous rt-PA administration. Plasma creatine kinase-MB fraction (CK-MB)
      levels were measured every 6 h for 24 h, and C-reactive protein levels were
      measured daily for 3 days. RESULTS: Group 1 had lower peak plasma CK-MB (141.9 +/
      28.3 vs. 203.8 +/- 23.3 IU/liter [mean +/- SEM], p < 0.014) and C-reactive
      protein levels (16 +/- 4 vs. 28 +/- 4 mg/liter on day 1; 26.6 +/- 5.5 vs. 61.8 +/
      14.4 mg/liter on day 2; 19.6 +/- 4.2 vs. 40.6 +/- 6.5 mg/liter on day 3, p <
      0.012) and a higher left ventricular ejection fraction (62.9 +/- 4% vs. 51.1 +/-
      5%, p < 0.04) than group 2. Group 1 had lower plasma t-PA antigen levels (15.6
      vs. 27 micrograms/liter, p < 0.006) but higher prothrombin fragment F1 + 2 (1.8
      vs. 1.1 nmol/liter, p < 0.003) and soluble fibrin levels (66.8 vs. 31 nmol/liter,
      p < 0.01). Coronary patency at 90 min was similar. CONCLUSIONS: Early spontaneous
      intermittent reperfusion during acute myocardial infarction is associated with
      augmented thrombogenic activity and less subsequent myocardial damage. This
      finding is consistent with a protective effect of intermittency on the myocardium
      and a procoagulant effect of spontaneous lysis on blood. It may also reflect a
      different rate of evolution of coronary thrombosis and myocardial infarction in
      patients with and those without spontaneous intermittent myocardial reperfusion.

PMID- 7642857
TI  - Contemporary reperfusion therapy for cardiogenic shock: the GUSTO-I trial
      experience. The GUSTO-I Investigators. Global Utilization of Streptokinase and
      Tissue Plasminogen Activator for Occluded Coronary Arteries.
AB  - OBJECTIVES: This study sought to examine the incidence, temporal profile and
      clinical implications of shock in a large trial of thrombolytic therapy for acute
      myocardial infarction. BACKGROUND: Despite advances in the treatment of acute
      ischemic syndromes, cardiogenic shock remains associated with significant
      morbidity and mortality. METHODS: Patients who presented within 6 h of symptom
      onset were randomized to four treatment strategies: 1) streptokinase plus
      subcutaneous heparin; 2) streptokinase plus intravenous heparin; 3) accelerated
      recombinant tissue-type plasminogen activator (rt-PA) plus intravenous heparin;
      or 4) streptokinase and rt-PA plus intravenous heparin. The primary end point was
      30-day all-cause mortality. RESULTS: Shock occurred in 2,972 patients (7.2%): 315
      (11%) had shock on arrival, and 2,657 (89%) developed shock after hospital
      admission. Reinfarction occurred in 11% of patients who developed shock compared
      with 3% of patients without shock. The mortality rate was significantly higher in
      patients who presented with (57%) or developed (55%) shock than in those without
      shock (3%) (p < 0.001). Shock developed significantly less frequently in patients
      receiving rt-PA. There were fewer deaths in patients who presented with shock and
      were treated with streptokinase plus intravenous heparin or who developed shock
      and were treated with streptokinase plus subcutaneous heparin. Patients who
      developed shock had a significantly lower 30-day mortality rate if angioplasty
      was performed. CONCLUSIONS: Because cardiogenic shock occurred most often after
      admission and with recurrent ischemia and reinfarction, recognizing signs of
      incipient shock may improve outcome. Fewer patients treated with rt-PA developed
      shock, yet those developing shock had the same high mortality rate as those
      presenting with shock, regardless of treatment. Only angioplasty was associated
      with a significantly lower mortality rate.

PMID- 7642858
TI  - ST segment tracking for rapid determination of patency of the infarct-related
      artery in acute myocardial infarction.
AB  - OBJECTIVES: This study was designed to test the hypothesis that monitoring the ST
      segment on a single electrocardiographic (ECG) lead reflecting activity in the
      infarct zone provides sensitive and specific recognition of reperfusion within 60
      min of initiation of therapy in acute myocardial infarction. BACKGROUND: Infarct
      related arteries that fail to recanalize early may benefit from immediate rescue
      angioplasty. Hence, detection of reperfusion has important practical clinical
      implications. METHODS: Of 41 patients with acute myocardial infarction who had
      ambulatory ECG (Holter) monitors placed, 38 had adequate ST segment monitoring
      for 3 h; 35 of the 38 were treated with thrombolytic agents and 3 with primary
      angioplasty. All patients underwent early coronary angiography and were
      classified into two groups: Group P (22 patients) had angiographic patency
      (Thrombolysis in Myocardial Infarction [TIMI] grade 2 or 3 flow), the Group O (16
      patients) had persistent occlusion (TIMI grade 0 or 1 flow) of the infarct
      related vessel at 60 min from initiation of therapy. The initial ST segment level
      was defined as the first ST segment level recorded; the peak ST segment level was
      defined as the highest ST segment level measured during the 1st 60 min. To assess
      the optimal ST segment recovery criteria for reperfusion, the presence or absence
      of a > or = 75%, > or = 50% and > or = 25% decrement from initial and peak ST
      segment levels, sampled and analyzed at 2.5-, 5-, 10-, 15-and 20-min intervals,
      was correlated with patency of the infarct-related artery at 60 min. RESULTS: ST
      segment recovery of > or = 50% reduction from peak ST segment levels with
      sampling rates at < or = 10-min intervals provided the optimal criterion for
      recognizing coronary artery patency at 60 min (sensitivity 96%, 95% confidence
      interval [CI] 77% to 99%; specificity 94%, 95% CI 69% to 99%, p < 0.0001). The
      subgroup of 13 patients in Group P with TIMI grade 3 reperfusion flow all met
      this criterion (sensitivity 100%, 95% CI 75% to 100%). The use of the initial ST
      segment level as the baseline for determining the presence of a > or = 50%
      reduction in ST segment levels within 60 min was less sensitive. Prediction of
      coronary reperfusion within 60 min of therapy on the basis of a > or = 75%
      decrement from peak ST segment levels was less sensitive, and the use of a > or =
      25% decrement was less specific. CONCLUSIONS: ST segment monitoring of a single
      lead reflecting the infarct zone provides a reliable method for assessing
      reperfusion within 60 min of acute myocardial infarction. Optimal criteria for
      ECG reperfusion include a > or = 50% decrease from peak ST segment levels, with
      ST segment measurements recorded continuously or at least every 10 min.

PMID- 7642859
TI  - ST segment analysis for determining the dynamic status of reperfusion therapy.

PMID- 7642860
TI  - Baseline and 6-month costs of primary angioplasty therapy for acute myocardial
      infarction: results from the primary angioplasty registry.
AB  - OBJECTIVES: This study sought to describe the economic outcomes from a
      prospective multicenter registry of primary coronary angioplasty. BACKGROUND:
      Interest in coronary angioplasty without preceding thrombolytic therapy as a
      primary reperfusion strategy has increased as a result of three recent randomized
      trials showing outcomes equivalent to or better than standard thrombolytic
      therapy. METHODS: The Primary Angioplasty Registry enrolled 270 patients with
      acute myocardial infarction at six private tertiary care medical centers.
      Baseline and follow-up medical costs and counts of resources consumed were
      collected from enrollment to the 6-month follow-up visit. Correlates and
      predictors of cost were identified with multivariable linear regression modeling.
      RESULTS: Ninety-five percent of patients had a revascularization procedure during
      the baseline hospital period: 85% had coronary angioplasty only; 4% had coronary
      bypass surgery only; 6% had both procedures. The total mean baseline hospital
      cost (not charge) was $13,113, with mean physician fees of $5,694. During the
      follow-up period, repeat coronary angiography was performed in 21% of patients,
      whereas 13% had repeat angioplasty and 3% bypass surgery. Mean hospital follow-up
      costs were $3,174, with mean physician fees of $1,443. Independent correlates of
      higher baseline hospital costs included older age (p = 0.049), anterior
      infarction (p = 0.03), initial Killip class (p < 0.0001), more severe coronary
      disease (p = 0.0015), need for bypass surgery alone or in addition to angioplasty
      (p < 0.0001) and recurrent ischemia (p < 0.0001). CONCLUSIONS: Costs of primary
      angioplasty for patients with acute myocardial infarction eligible for
      thrombolysis were strongly influenced by infarction- and procedure-related
      complications but only modestly influenced by patient selection factors.

PMID- 7642861
TI  - Spontaneous regression of restenosis: an angiographic study.
AB  - OBJECTIVES: This study was designed to examine the possibility that spontaneous
      regression in stenosis severity occurs over time in patients with restenosis
      after percutaneous transluminal coronary angioplasty. BACKGROUND: The underlying
      mechanisms of restenosis are intimal hyperplasia and smooth muscle cell
      proliferation in response to vascular injury. We hypothesized that the initial
      hyperplastic response is followed by dynamic remodeling and eventual spontaneous
      regression, leading to stabilization or a reduction in stenosis severity.
      METHODS: A total of 136 patients participated in a trial to evaluate the efficacy
      of fish oil versus placebo in preventing restenosis after angioplasty. One
      hundred thirteen patients completed this study with angiographic follow-up, of
      whom 56 had restenosis. Of these, 19 were asymptomatic and did not undergo repeat
      revascularization; 15 consented in a separate study to undergo repeat
      angiography, which was performed 6 to 25 months later to assess the possibility
      of regression. RESULTS: There was a significant mean (+/- SD) decrease in lesion
      severity from 66.9 +/- 8.7% to 47.5 +/- 9.0% (p < 0.0001) and a significant mean
      increase in minimal lumen diameter from 0.91 +/- 0.31 mm to 1.44 +/- 0.35 mm (p <
      0.0001). No patient showed progression of stenosis, but regression of restenosis,
      defined as a decrease in minimal lumen diameter > or = 0.2 mm, was noted in 12 of
      the patients. CONCLUSIONS: Although all 15 study patients were asymptomatic,
      similar changes may occur in symptomatic patients. A trial of medical therapy may
      be appropriate in asymptomatic or mildly symptomatic patients before further
      interventions. This strategy would avoid unnecessary invasive procedures, prevent
      a "restenosis cycle" and result in significant cost savings.

PMID- 7642862
TI  - Restenosis: the "hole" truth?

PMID- 7642863
TI  - Immediate results and late outcomes after stent implantation in saphenous vein
      graft lesions: the multicenter U.S. Palmaz-Schatz stent experience. The Palmaz
      Schatz Stent Study Group.
AB  - OBJECTIVES: This study reports the multicenter registry experience evaluating the
      safety and efficacy of the Palmaz-Schatz stent in the treatment of saphenous vein
      graft disease. BACKGROUND: Saphenous vein graft angioplasty is associated with
      frequent periprocedural complications and a high frequency of restenosis. Stent
      implantation has been shown to reduce restenosis, with improved long-term
      outcomes in the treatment of native coronary artery disease. Preliminary
      experience with stent placement in the treatment of saphenous vein graft lesions
      has been favorable. METHODS: Twenty U.S. investigator sites enrolled a total of
      589 symptomatic patients (624 lesions) for treatment of focal vein graft stenoses
      between January 1990 and April 1992. Follow-up angiography was performed at 6
      months, and the clinical course of all study patients was prospectively collected
      at regular intervals for up to 12 months. RESULTS: Stent delivery was successful
      in 98.8% of cases, and the procedural success rate was 97.1%. The lesion diameter
      stenosis decreased from 82 +/- 12% (mean +/- SD) before to 6.6 +/- 10.2% after
      treatment. Major in-hospital complications occurred in 17 patients (2.9%); stent
      thrombosis was found in 8 (1.4%); and major vascular or bleeding complications
      were noted in 83 (14.3%). Six-month angiographic follow-up revealed an overall
      restenosis rate (> or = 50% diameter stenosis) of 29.7%. Multivariate logistic
      regression analysis indicated that 1) restenotic lesions, 2) smaller reference
      vessel size, 3) history of diabetes mellitus, and 4) higher percent poststent
      diameter stenosis were independent predictors of restenosis. The 12-month
      actuarial event-free survival was 76.3%. CONCLUSIONS: Stent implantation in
      patients with focal saphenous vein graft lesions can be achieved with a high rate
      of procedural success, acceptable major complications, reduced angiographic
      restenosis and favorable late clinical outcome compared with historical balloon
      angioplasty control series. The rigorous anticoagulation regimen after stent
      placement results in more frequent vascular and other bleeding complications.
      Future randomized studies comparing standard balloon angioplasty with stent
      implantation are warranted to properly assess the full impact of stent placement
      in the treatment of saphenous vein graft lesions.

PMID- 7642864
TI  - Intracoronary stent insertion after balloon angioplasty of chronic total
      occlusions.
AB  - OBJECTIVES: This retrospective analysis was performed to assess the medium-term
      effectiveness of implanting intracoronary stents into chronic total occlusions
      that are successfully opened by balloon angioplasty. BACKGROUND: The value of
      percutaneous transluminal coronary angioplasty of chronic total occlusions is
      limited by a very high restenosis rate of 50% to 68%. Intravascular stents have
      been shown to reduce restenosis in a subset of patients with subtotal stenoses.
      It has not been demonstrated that the placement of stents into successfully
      opened chronic total coronary artery occlusions leads to lower rates of
      restenosis. METHODS: A consecutive series of patients with chronic total coronary
      occlusions successfully opened by balloon angioplasty received Palmaz-Schatz
      stents. Patients underwent clinical and angiographic follow-up at a mean of 6
      months after stent insertion. Angiographic and clinical results were
      retrospectively analyzed. RESULTS: Fifty-nine patients underwent stenting of 60
      chronic total coronary occlusions, with a 98% rate of successful stent
      deployment. Complications occurred in 5% of cases, all with subacute thrombosis.
      Angiographic follow-up was obtained in 88% of patients at a mean of 6 months and
      demonstrated an angiographic restenosis rate of 20%, with only one reocclusion.
      Among several variables examined, only the presence of a procedure-related
      moderate to severe dissection was associated with higher follow-up percent
      diameter stenoses and clinical events. At a mean of 14 months after stent
      insertion, 77% of patients remained free of symptoms or clinical events.
      CONCLUSIONS: The implantation of intracoronary stents into vessels with opened
      chronic total coronary occlusions is associated with favorable rates of
      angiographic restenosis and relief of symptoms. A randomized clinical trial
      comparing balloon angioplasty with stent-assisted balloon angioplasty in the
      treatment of chronic total coronary occlusions is indicated.

PMID- 7642865
TI  - Small stent size and intimal hyperplasia contribute to restenosis: a volumetric
      intravascular ultrasound analysis.
AB  - OBJECTIVES: The purpose of this study was to use volumetric intravascular
      ultrasound analysis of Palmaz-Schatz stents to assess the in-stent restenotic
      process. BACKGROUND: By reducing lesion elastic recoil and chronic arterial
      remodeling, stents improve the long-term results of coronary angioplasty.
      However, stents are prone to the development of neointimal hyperplasia.
      Angiographic studies of stent restenosis have suggested that these hyperplastic
      responses are the cause of in-stent restenosis; however, it is difficult to
      visualize the radiolucent Palmaz-Schatz stent by angiography. Intravascular
      ultrasound provides detailed cross-sectional imaging of the coronary arteries,
      especially the intense metallic reflection of endovascular stents. METHODS: Forty
      four patients with 60 Palmaz-Schatz stents underwent intravascular ultrasound
      imaging at follow-up ([mean +/- SD] 8.8 +/- 7.2 months after implantation).
      Thirty-four stents were placed in saphenous vein grafts and 26 in native coronary
      arteries; 30 were placed in restenotic lesions. Intravascular ultrasound with
      automatic transducer pullback at 0.5 mm/s allowed measurement of stent, lumen and
      intimal hyperplasia cross-sectional areas at 1-mm axial increments within the
      stents. Using Simpson's rule, stent, lumen and intimal hyperplasia volumes were
      calculated. Patterns of in-stent restenosis were then identified. RESULTS:
      Restenotic stents had smaller stent volumes (120 +/- 41 vs. 147 +/- 43 mm3, p =
      0.016) and lumen volumes (62 +/- 28 vs. 118 +/- 42 mm3, p < 0.0001) but larger
      intimal hyperplasia volumes (58 +/- 36 vs. 29 +/- 18 mm3, p < 0.001) than
      nonrestenotic stents. A focal restenosis pattern was more common (20 [77%] of 26)
      than a diffuse restenosis pattern (6 [23%] of 26). Stents with focal restenosis
      and stents with diffuse restenosis had equally small stent volumes (120 +/- 44
      vs. 120 +/- 31 mm3, respectively, p = NS); however, stents with diffuse
      restenosis had larger intimal hyperplasia volumes (84 +/- 30 vs. 50 +/- 34 mm3, p
      < 0.05). Focal restenosis was most commonly located at the central articulation
      (45%); the location of focal restenosis was related to the focal accumulation of
      neointimal tissue. CONCLUSIONS: Stent volume and magnitude and distribution of
      intimal hyperplasia are important in the development of in-stent restenosis.
      Stent volume was smaller and intimal hyperplasia volume greater in restenotic
      stents. Stent restenosis is more commonly focal in nature and located at the
      central articulation.

PMID- 7642866
TI  - Intravascular ultrasound after low and high inflation pressure coronary artery
      stent implantation.
AB  - OBJECTIVES: We sought to characterize the differences seen after low or high
      pressure coronary artery stent deployment as assessed by intravascular
      ultrasound. BACKGROUND: Until 1992, the success of stent deployment was assessed
      by angiographic criteria only, but in 1993 the procedure was expanded to include
      postprocedural single-use intravascular ultrasound imaging. Ultrasound criteria
      for successful stent deployment were 1) symmetry, 2) minimal lumen diameter > 3.0
      mm, 3) no echo-free spaces between the stent and the vessel, and 4) no uncovered
      dissections. METHODS: We used mechanical 4.8F or 3.5F 20- or 30-MHz monorail
      single-use intravascular ultrasound catheters. RESULTS: Fifty-two patients were
      included, 28 treated in 1991 and 1992 (group A) and 24 treated in 1993 or 1994
      (group B); 87% of patients underwent elective stent implantation. The number of
      echocardiographic studies per patient increased from 1 +/- 0.1 (mean +/- SD) in
      group A to 2.0 +/- 0.85 in group B. Mean maximal balloon size increased from 3.3
      +/- 0.33 to 3.73 +/- 0.24 mm and maximal inflation pressure from 6.9 +/- 1.1 to
      15.8 +/- 2.4 bar (p < 0.001). The eccentricity index was 0.915 +/- 0.04 in group
      B versus 0.87 +/- 0.05 in group A. Minimal lumen diameter measured by
      echocardiography increased from 2.55 +/- 0.41 mm in group A to 3.14 +/- 0.37 mm
      in group B. The final mean values per cross-sectional area as a percent of
      calculated balloon area were similar in group A (67.5 +/- 23%) and group B (66.5
      +/- 22.9%). No major acute complications occurred in either group; subacute
      thrombosis developed in two patients, both in group A. CONCLUSIONS: Intravascular
      ultrasound data confirm that high pressure stent deployment leads to increased
      minimal lumen area. Despite high pressure stent deployment, homogeneous stent
      geometry and optimal stent expansion were not observed in all patients.

PMID- 7642867
TI  - High speed rotational atherectomy: outcome in calcified and noncalcified coronary
      artery lesions.
AB  - OBJECTIVES: This study sought to determine the success and complication rates of
      high speed rotational coronary atherectomy in calcified and noncalcified lesions.
      BACKGROUND: Percutaneous transluminal coronary angioplasty and directional
      coronary atherectomy of calcified lesions are associated with reduced procedural
      success and increased complications. Rotational atherectomy using the Rotablator
      catheter abrades noncompliant plaque and may improve outcome in calcified
      lesions. METHODS: Data from the completed Multicenter Rotablator Registry of
      2,161 rotational atherectomy procedures in single lesions were analyzed to
      determine the relative efficacy of rotational atherectomy for 1,078 calcified and
      1,083 noncalcified lesions. The power of the study was 0.86 to detect a
      significant difference in outcome, if the true success rates in the noncalcified
      and calcified lesions were 96% and 93%, respectively. RESULTS: Patients with
      calcified lesions were older (mean [+/- SD] age 66.2 +/- 10.3 vs. 60.5 +/- 11.0
      years, p = 0.0001) than those with noncalcified lesions. Calcified lesions were
      more frequently new (75% vs. 64%, p = 0.0001), angulated (27% vs. 22%, p = 0.02),
      eccentric (75% vs. 64%, p = 0.0001) and long (32% vs. 27%, > 10 mm in length, p =
      0.01). They were also more often complex (57% vs. 46%, p = 0.001) and located in
      the left anterior descending coronary artery (51% vs. 44%, p = 0.001). Adjunctive
      coronary angioplasty was used in 82.9% of calcified and 66.9% of noncalcified
      lesions. Procedural success, defined as < 50% residual stenosis without major
      complications, was achieved in 94.3% of calcified and 95.2% of noncalcified
      lesions (p = 0.32). Major complication rates were 4.1% in calcified and 3.1% in
      noncalcified lesions (p = 0.24). Non-Q wave myocardial infarction was documented
      in 10.0% of calcified and 7.7% of noncalcified lesions (p = 0.054). Mean
      postprocedural residual stenosis was 21.6 +/- 13.9% in calcified and 23.3 +/- 15%
      in noncalcified lesions (p = 0.39). CONCLUSIONS: In this review of data from a
      large multicenter registry, the success rate of rotational atherectomy was not
      reduced by calcification despite the more frequent complex nature of the
      calcified lesions. The Rotablator catheter is likely to be the device of choice
      for percutaneous intervention in calcified lesions, but definitive conclusions
      await the results of randomized trials.

PMID- 7642868
TI  - Functional and morphologic adaptation of undersized donor hearts after heart
      transplantation.
AB  - OBJECTIVES: This study analyzes our experience with transplantation of small
      donor hearts in a subgroup of moribund patients who could not be bridged to
      transplantation with mechanical assist devices. BACKGROUND: The major problem
      facing transplant programs in the United States is the lack of donor heart
      availability. One method of expanding the donor pool may be to liberalize the
      criteria for an acceptable donor heart. METHODS: We analyzed the growth and
      adaptation of 14 undersized and 14 conventionally sized donor hearts over a
      period of 10 weeks after heart transplantation. The left ventricular systolic and
      diastolic diameters, septal and posterior wall thicknesses, left ventricular mass
      calculated by the Penn convention and left ventricular ejection fraction were
      obtained by M-mode and two-dimensional echocardiography and documented by a
      single reader in blinded manner. Echocardiographic measurements were obtained
      before implantation and at 5 and 10 weeks after orthotopic heart transplantation.
      RESULTS: The mean (+/- SD) donor/recipient weight ratios were 0.53 +/- 0.06 for
      undersized hearts and 0.98 +/- 0.05 for normal-sized hearts. All 28 patients
      received similar immunosuppressive regimens, including intravenous steroids,
      cyclosporine and azathioprine. The length of hospital stay after transplantation
      did not vary significantly between the two groups. All the patients had at least
      one rejection episode during the 10-week study period. There was a tendency
      toward higher pulmonary pressures in undersized hearts, which was not
      statistically significant. Heart rate was significantly higher for undersized
      hearts, due in part to the use of theophylline or terbutaline to maintain
      tachycardia. There was a significant increase in left ventricular systolic and
      diastolic dimensions in undersized hearts compared with conventionally sized
      hearts. Undersized hearts increased in left ventricular mass over the 10-week
      period, whereas the conventionally sized donor hearts did not change between 5
      and 10 weeks. CONCLUSIONS: In undersized hearts the increase in left ventricular
      mass and internal dimensions, with preservation of the posterior/septal wall
      thickness ratio, suggests that the left ventricle adapts to the larger recipient
      circulation early after transplantation. Despite denervation and a mismatched
      load, undersized transplanted hearts adapt appropriately to their new hemodynamic
      milieu.

PMID- 7642869
TI  - Heart transplantation in children with congenital heart disease.
AB  - OBJECTIVES: The aim of this study was to describe heart transplantation in
      children with congenital heart disease and to compare the results with those in
      children undergoing transplantation for other cardiac diseases. BACKGROUND:
      Reports describe decreased survival after heart transplantation in children with
      congenital heart disease compared with those with cardiomyopathy. However,
      transplantation is increasingly being considered in the surgical management of
      children with complex congenital heart disease. Present-day results from this
      group require reassessment. METHODS: The diagnoses, previous operations and
      indications for transplantation were characterized in children with congenital
      heart disease. Pretransplant course, graft ischemia time, post-transplant
      survival and outcome (rejection frequency, infection rate, length of hospital
      stay) were compared with those in children undergoing transplantation for other
      reasons (n = 47). RESULTS: Thirty-seven children (mean [+/- SD] age 9 +/- 6
      years) with congenital heart disease underwent transplantation; 86% had undergone
      one or more previous operations. Repair of extracardiac defects at
      transplantation was necessary in 23 patients. Causes of death after
      transplantation were donor failure in two patients, surgical bleeding in two,
      pulmonary hemorrhage in one, infection in four, rejection in three and graft
      atherosclerosis in one. No difference in 1- and 5-year survival rates (70% vs.
      77% and 64% vs. 65%, respectively), rejection frequency or length of hospital
      stay was seen between children with and without congenital heart disease.
      Cardiopulmonary bypass and donor ischemia time were significantly longer in
      patients with congenital heart disease. Serious infections were more common in
      children with than without congenital heart disease (13 of 37 vs. 6 of 47,
      respectively, p = 0.01). CONCLUSIONS: Despite the more complex cardiac surgery
      required at implantation and longer donor ischemic time, heart transplantation
      can be performed in children with complex congenital heart disease with success
      similar to that in patients with other cardiac diseases.

PMID- 7642870
TI  - Echocardiographic-morphologic correlations in tricuspid atresia.
AB  - OBJECTIVES: Our aim was to clarify the anatomic substrate in hearts diagnosed as
      having tricuspid atresia by studying autopsy specimens and comparing the findings
      with those in two-dimensional echocardiograms. BACKGROUND: Traditionally,
      tricuspid atresia was thought, and is still believed by some, to be due to an
      imperforate valvular membrane interposed between the floor of the blind-ending
      right atrium and the hypoplastic right ventricle. Others argued that the dimple,
      when present, pointed to the outflow tract of the left ventricle rather than to
      the right ventricle, making the lesion more akin to double-inlet left ventricle.
      METHODS: We examined 39 autopsy specimens catalogued as having tricuspid atresia.
      We then studied 24 two-dimensional echocardiograms from patients with a primary
      diagnosis of tricuspid atresia. RESULTS: Of the 39 specimens, 37 had a completely
      muscular floor to the right atrium (absent right atrioventricular [AV]
      connection). The dimple, when identified, was (except in one case) directed to
      the left ventricular outflow tract. Only two hearts had an imperforate tricuspid
      valve. Two-dimensional echocardiograms in all cases showed an echo-dense band,
      produced by the fibrofatty tissue of the AV groove and representing absence of
      the right AV connection, between the muscular floor of the morphologically right
      atrium and the ventricular mass. CONCLUSIONS: Tricuspid atresia is usually, but
      not always, due to morphologic absence of one AV connection. In most cases, the
      ventricular mass then comprises a dominant left ventricle together with a
      rudimentary and incomplete right ventricle.

PMID- 7642871
TI  - Transthoracic three-dimensional echocardiography in adult patients with
      congenital heart disease.
AB  - OBJECTIVES: This study sought to assess both the feasibility and potential role
      of transthoracic three-dimensional echocardiography for the evaluation of adult
      patients with congenital heart disease. BACKGROUND: The unrestricted views with
      depth perception provided by three-dimensional echocardiography with dynamic
      volume-rendered display may enhance visualization of cardiac structures and
      detection of abnormalities in patients with congenital heart defects. METHODS: We
      studied 33 patients with various heart defects (mitral valve anomalies in 9,
      aortic valve anomalies in 5, subaortic membrane in 5, ventricular septal defect
      in 4, transposition of the great arteries in 3, tetralogy of Fallot in 2, other
      defects in 5). Cross-sectional images of the specific region of interest were
      acquired from either the parasternal or apical window with the rotational
      technique (2 degrees interval with electrocardiographic and respiratory gating)
      and postprocessed for resampling in cubic format. From these three-dimensional
      data sets a multitude of cut planes were selected, presented in volume-rendered
      dynamic display and analyzed by two observers for comparison with standard two
      dimensional images to assess their additional information. RESULTS: Three
      dimensional reconstruction was possible in all patients. Structures of interest
      were evaluated from unusual viewpoints, providing both cardiologists and surgeons
      with immediate feedback. When compared with standard two-dimensional images,
      additional information was provided for 12 patients (36%). The mitral valve,
      aortoseptal continuity and interatrial septum were the structures for which three
      dimensional echocardiography was most useful. CONCLUSIONS: Transthoracic three
      dimensional echocardiography is feasible and facilitates spatial recognition of
      the intracardiac anatomy in a significant proportion of patients and enhances
      diagnostic confidence of complex congenital heart disease.

PMID- 7642872
TI  - Salutary effect of disopyramide on left ventricular diastolic function in
      hypertrophic obstructive cardiomyopathy.
AB  - OBJECTIVES: The purpose of this study was to estimate the effect of disopyramide
      on left ventricular diastolic function in patients with hypertrophic obstructive
      cardiomyopathy. BACKGROUND: Although disopyramide has been reported to lessen
      clinical symptoms in patients with hypertrophic obstructive cardiomyopathy, few
      data exist regarding its effect on diastolic function in these patients. METHODS:
      Thirteen patients with hypertrophic cardiomyopathy (six with and seven without
      left ventricular outflow obstruction) were examined. Before and after intravenous
      disopyramide, hemodynamic and angiographic studies were performed. RESULTS: In
      patients with outflow obstruction, pressure gradient at the outflow tract
      decreased from a mean +/- SD of 100 +/- 45 to 26 +/- 33 mm Hg (p < 0.01).
      Although systolic function was similarly impaired in both groups, the time
      constant of left ventricular pressure decay (tau) shortened from 56 +/- 10 to 44
      +/- 8 ms (p < 0.01) and the constant of left ventricular chamber stiffness (kc)
      decreased from 0.049 +/- 0.017 to 0.038 +/- 0.014 m2/ml (p < 0.01) only in
      patients with outflow obstruction. Shortening in tau correlated best with
      decrease in left ventricular systolic pressure (r = 0.84, p < 0.01). In contrast,
      tau was prolonged from 52 +/- 10 to 64 +/- 11 ms (p < 0.01) and kc was unchanged
      in patients without outflow obstruction. CONCLUSIONS: The primary effects of
      disopyramide on the hypertrophied left ventricle were negative inotropic and
      negative lusitropic. However, left ventricular diastolic properties in patients
      with outflow obstruction were improved with a decrease in outflow pressure
      gradient. Relief of clinical symptoms in hypertrophic obstructive cardiomyopathy
      with disopyramide might be due in part to improvement of diastolic function,
      which appears secondary to the reduction in ventricular afterload.

PMID- 7642873
TI  - Postoperative lead-related complications in patients with nonthoracotomy
      defibrillation lead systems.
AB  - OBJECTIVES: This study sought to document postoperative complications
      attributable to nonthoracotomy defibrillation lead systems in a large cohort.
      BACKGROUND: The incidence of postoperative complications specifically associated
      with nonthoracotomy defibrillation lead systems is unknown. METHODS:
      Postoperative lead-related complications were evaluated in 170 patients with a
      nonthoracotomy defibrillation lead system who were followed up for a mean (+/-
      SD) of 17 +/- 12 months. Each system incorporated one or more intravascular
      leads. In 117 patients (69%), the system incorporated a subcutaneous
      defibrillation patch. All implantations were performed in an operating room by
      cardiothoracic surgeons. Defibrillation thresholds were measured at implantation,
      before hospital discharge (mean 3 +/- 2 days) and at 4 to 18 weeks after
      implantation. Patients were evaluated every 2 to 3 months after implantation or
      as indicated by clinical exigency. RESULTS: Twenty-seven patients (15.9%) were
      diagnosed with a lead-related complication that either extended the initial
      hospital period or led to a second hospital admission. Complications included
      endocardial lead or subcutaneous defibrillation patch dislodgment in eight
      patients (4.7%), which was diagnosed between 2 and 345 days after implantation;
      endocardial or subcutaneous patch lead fracture in six (3.5%), which was
      diagnosed between 53 and 600 days after implantation; subcutaneous patch mesh
      fracture in one, which was diagnosed at 150 days after implantation; subclavian
      vein thrombosis in three (1.8%), which was diagnosed at 2 to 50 days after
      implantation; and unacceptably elevated defibrillation threshold (within 5 J of
      maximal device output) in nine (5.3%), which was documented at one of the two
      postimplantation evaluations in eight patients or at the time of failure to
      terminate a spontaneous ventricular tachycardia in one. Seventeen of the 27
      patients required reoperation for correction of their complication. In addition,
      system infection requiring complete explantation occurred in seven other patients
      (4.1%) at an interval from implantation ranging from 14 to 120 days. CONCLUSIONS:
      Postoperative complications related to a nonthoracotomy defibrillation lead
      system were common and frequently required reoperation for correction. The rate
      of system explantation due to infection was also significant. Postoperative
      defibrillation testing and vigilant outpatient follow-up evaluation are necessary
      to ensure normal lead function.

PMID- 7642874
TI  - Mexiletine antagonizes effects of sotalol on QT interval duration and its
      proarrhythmic effects in a canine model of torsade de pointes.
AB  - OBJECTIVES: The arrhythmogenic and electrophysiologic properties of sotalol, a
      class III antiarrhythmic drug, administered alone and in combination with
      mexiletine, a class I antiarrhythmic drug, were compared in conscious dogs
      predisposed to torsade de pointes arrhythmias. BACKGROUND: The utility of sotalol
      is limited by proarrhythmia related to excessive delays in repolarization. The
      addition of mexiletine may limit the risk of torsade de pointes because it
      reduced in vitro the sotalol-induced increase in action potential duration.
      METHODS: Two studies were performed in eight hypokalemic dogs (plasma potassium
      level < or = 3.2 mmol/liter) with chronic atrioventricular block (mean
      ventricular cycle length, RR 1,100 ms) at 3-day intervals using a crossover
      protocol. Intravenous sotalol (4.5 + 1.5 mg/kg body weight per h) alone was given
      for 2 h, or, on another day, an intravenous mexiletine infusion (4.5 + 1.5 mg/kg
      per h) was begun 30 min before sotalol infusion. Spontaneous ventricular cycle
      length and QT interval and ventricular effective refractory period at the 1,000
      ms pacing cycle length were measured at baseline and 30 min after the onset of
      each drug infusion. The electrocardiogram (ECG) was continuously monitored for
      torsade de pointes. RESULTS: Sotalol plus mexiletine and sotalol alone had a
      significant (p < or = 0.05) and similar effect on ventricular cycle length (+ 800
      +/- 93 vs. + 690 +/- 104 ms [mean +/- SEM]) and ventricular effective refractory
      period (+ 20 +/- 4 vs. + 25 +/- 4 ms), but sotalol plus mexiletine had a lesser
      effect on QT interval (+ 20 +/- 6 vs. + 50 +/- 8 ms, p < or = 0.05). Torsade de
      pointes is less frequent (one of eight dogs vs. six of eight dogs, p = 0.02) with
      sotalol plus mexiletine than with sotalol alone. CONCLUSIONS: The
      coadministration of a class Ib agent can reduce the proarrhythmic potential of a
      class III drug in experimental animals predisposed to torsade de pointes
      arrhythmias and further suggests the clinical utility of such a strategy.

PMID- 7642875
TI  - Intercellular adhesion molecule-1 induction: a sensitive and quantitative marker
      for cardiac allograft rejection.
AB  - OBJECTIVES: Rats with abdominal heterotopic heart transplants were studied to
      determine whether cardiac allograft rejection could be assessed by
      immunoscintigraphy targeting intercellular adhesion molecule-1 (ICAM-1), which
      was induced on allografted organ cells in association with rejection. BACKGROUND:
      It is important to detect early rejection before development of myocyte necrosis.
      Although a variety of methods for the detection of cardiac rejection have been
      investigated, histologic inspection of biopsied samples is still used routinely
      for clinical diagnosis of rejection. METHODS: DA rat (RT-1a) hearts were
      transplanted into PVG rats (RT-1c). Immunohistologic examination of the
      allografts demonstrated that ICAM-1 induction on vascular endothelial cells was
      observed as early as 4 days after transplantation in this combination. Thirty
      nine allografted rats and seven isografted rats were studied. One day after
      injection of 100 microCi of 111Inlabeled anti-ICAM-1 monoclonal antibody (1A29),
      planar images were obtained. RESULTS: Rejecting allografts showed increased
      radiotracer uptake and could be identified on the images as early as 5 days after
      transplantation. In contrast, nonrejecting cardiac allografts and isografts did
      not show specific uptake. Mildly rejecting allografts, with mononuclear cell
      infiltration but without significant myocyte necrosis, could be scintigraphically
      identified, and the level of radiotracer uptake reflected the histologic severity
      of rejection. Accumulation of 111In-labeled monoclonal antibody of isotype
      matched irrelevant specificity was not detected in the rejecting allografts.
      CONCLUSIONS: These data indicate that ICAM-1 induction can be assessed
      quantitatively by radioimmunoscintigraphy. Radioimmunoscitigraphy is a sensitive
      method for early detection and assessment of cardiac allograft rejection.

PMID- 7642876
TI  - Mechanisms of estrogen-induced vasodilation: in vivo studies in canine coronary
      conductance and resistance arteries.
AB  - OBJECTIVES: We sought to examine the immediate vasodilator effect of
      intracoronary estrogen on epicardial and resistance coronary arteries in 19 dogs.
      BACKGROUND: Although estrogen reportedly dilates coronary arteries in vitro, the
      site and mechanisms of its action have not been fully defined in vivo. METHODS:
      Epicardial coronary artery dimensions and coronary flow velocity were assessed
      using simultaneous intracoronary two-dimensional and Doppler ultrasound. RESULTS:
      Estrogen (0.1 and 1 mumol/liter) induced a significant increase in coronary cross
      sectional area, flow velocity and volumetric blood flow. Estrogen-induced
      vasodilation was not influenced either by pretreatment with N omega-nitro-L
      arginine methyl ester (L-NAME) (100 mumol/liter intracoronary), indomethacin (5
      mg/kg body weight intravenously), propranolol (0.75 mg/kg intravenously) or the
      classic estrogen receptor antagonist ICI 182,780 (10 mumol/liter). Balloon
      denudation of the endothelium did not attenuate estrogen-induced epicardial
      vasodilation. Pretreatment with glibenclamide (10 mumol/liter) attenuated
      estrogen-induced vasodilation only in epicardial arteries, as did verapamil (0.1
      mumol/liter). Estrogen had no effect on a phenylephrine dose-response curve in
      either epicardial coronary arteries or the microcirculation. CONCLUSIONS: Acute
      estrogen-induced dilation in canine coronary arteries is endothelium independent
      and is not mediated by the classic intracellular estrogen receptor but through
      non-genomic mechanisms, presumably at the membrane level, which in epicardial
      arteries may include effects on adenosine triphosphate-sensitive potassium or
      calcium channels, or both.

PMID- 7642877
TI  - Mechanical and metabolic functions in pig hearts after 4 days of chronic coronary
      stenosis.
AB  - OBJECTIVES: This study sought to evaluate the functional and metabolic
      consequences of imposing a chronic external coronary stenosis around the left
      anterior descending coronary artery for 4 days in an intact pig model.
      BACKGROUND: A clinical condition termed hibernating myocardium has been described
      wherein as a result of chronic sustained or intermittent coronary hypoperfusion,
      heart muscle minimizes energy demands by decreasing mechanical function and thus
      avoids cell death. The use of chronic animal models to stimulate this disorder
      may assist in establishing causative associations among determinants to explain
      this phenomenon. METHODS: A hydraulic cuff occluder was placed around the left
      anterior descending coronary artery in eight pigs. Coronary flow velocity was
      reduced by a mean (+/- SE) of 49 +/- 5% of prestenotic values, as estimated by a
      Doppler velocity probe. After 4 days the pigs were prepared with extracorporeal
      coronary circulation and evaluated at flow conditions dictated by the cuff
      occluder. Substrate utilizations were described using equilibrium labeling with
      [U-14C]palmitate and [5-3H]glucose. Results were compared with a combined group
      of 21 acute and chronic (4 day) sham animals. RESULTS: Four days of partial
      coronary stenosis significantly decreased regional systolic shortening by 54%.
      Myocardial oxygen consumption was maintained at aerobic levels, and rest coronary
      flows were normal. Fatty acid oxidation was decreased by 43% below composite sham
      values, and exogenous glucose utilization was increased severalfold. Alterations
      in myocardial metabolism were accompanied by a decline in tissue content of
      adenosine triphosphate. CONCLUSIONS: These data suggest that chronic coronary
      stenosis in the absence of macroscarring imparts an impairment in mechanical
      function, whereas coronary flow and myocardial oxygen consumption are preserved
      at rest. The increases in glycolytic flux of exogenous glucose are similar to
      observations on glucose uptake assessed by fluorine-18 2-deoxy-2-fluoro-D-glucose
      in patients with advanced coronary artery disease. We speculate that intermittent
      episodes of ischemia and reperfusion are the cause of this phenomenon.

PMID- 7642878
TI  - Gene therapy for the vulnerable plaque.
AB  - Acute coronary events result from the rupture of an atherosclerotic plaque,
      leading to formation of an occlusive coronary thrombus. Recent developments in
      the field of gene transfer provide the opportunity to genetically modify cells
      involved in plaque rupture as well as thrombus formation and thus prevent acute
      coronary syndromes. A first approach consists of transferring genes, the product
      of which may stabilize the vulnerable plaque by reducing the plaque content in
      lipids and macrophages. Alternatively, the introduction into the atherosclerotic
      plaque of genes encoding for thrombolytic proteins or growth factors able to
      restore physiologic antithrombotic functions of endothelial cells may inhibit
      thrombus formation should the plaque rupture. The success of such strategies
      depends on the efficiency with which the transgene is introduced and expressed
      into the target cell, the duration of transgene expression and the ability of the
      transgene product to ultimately prevent plaque rupture or thrombus formation, or
      both.

PMID- 7642879
TI  - Sensationalism and the news media.

PMID- 7642880
TI  - Long-term digoxin therapy.

PMID- 7642881
TI  - Exercise-induced mitral regurgitation and antibiotic prophylaxis against
      infective endocarditis in mitral valve prolapse.

PMID- 7642882
TI  - International comparisons of waiting times for cardiovascular procedures.

PMID- 7642884
TI  - The American Dietetic Association 78th annual meeting. Chicago, Illinois, October
      30-November 2, 1995. Abstracts.

PMID- 7642883
TI  - Reuse of balloon catheters for coronary angioplasty.

PMID- 7642885
TI  - Junk science--is peer review the answer?

PMID- 7642886
TI  - Parasitic infections of the central nervous system in children. Part III: Space
      occupying lesions.
AB  - In the last part of this three-part review of parasitic infections of the central
      nervous system in children, we consider parasites which due to their size,
      distribution, or the nature of the host response, tend to cause focal lesions in
      the brain and spinal cord and therefore present as space-occupying lesions which
      occasionally mimic malignant tumors. As in Parts I and II, infections are grouped
      according to their predominant geographic area. Such infections include
      cysticercosis, one of the more common and important infections of the central
      nervous system.

PMID- 7642888
TI  - Persistent respiratory failure due to low cervical cord infarction in newborn
      babies.
AB  - Perinatal infarction of the spinal cord is described in two premature babies who
      survived for several months. In both cases, there was bilateral, multisegmental
      infarction at the lower cervicothoracic arterial zone (inferior cervical sector),
      predominantly within the territory of the anterior spinal artery. Clinically,
      both infants had acute respiratory failure, diaphragmatic respiration,
      intercostal paralysis, bell-shaped deformity of the thorax, and bilateral arm
      paresis. Intubation and ventilator support were required for weeks. Eventual
      extubation was followed by recurrent respiratory failure, atelectasis, and
      pneumonia. At the level of the infarction, multiple, scattered scars were found
      in central, perimedullary, and intramedullary arteries, but not in their parent
      vessels. The etiology of the angiopathy was not determined. These cases
      demonstrate that discrete arterial infarction of the cord can occur in premature
      babies, and that such a lesion should be considered in the differential diagnosis
      of neonatal respiratory failure.

PMID- 7642887
TI  - A review of leptomeningeal metastases in pediatrics.
AB  - Leptomeningeal metastasis is an uncommon problem in pediatric neurology and
      oncology. It occurs primarily in children with acute lymphoblastic leukemia and
      primary brain tumors. Although leptomeningeal metastasis may present with focal
      neurologic signs and symptoms, leptomeningeal metastasis is a disease affecting
      the entire neuraxis and necessitating an extent-of-disease evaluation of both the
      brain and spinal cord. Neuroradiographic staging of leptomeningeal metastases
      includes contrast-enhanced cranial computed tomography, magnetic resonance
      imaging, contrast-enhanced spine magnetic resonance imaging or computed
      tomographic myelography, and radionuclide cerebrospinal fluid flow studies. As a
      consequence of global neuraxis involvement, the treatment of leptomeningeal
      metastases requires therapy directed at all cerebrospinal fluid compartments. The
      treatment of leptomeningeal metastases usually includes both radiotherapy and
      intra-cerebrospinal fluid drug therapy. Radiotherapy is directed to regions of
      bulky or symptomatic central nervous system disease. Intra-cerebrospinal fluid
      drug therapy, using one of three available chemotherapeutic agents (methotrexate,
      cytarabine, or triethylene thiophosphoramide), is administered by a variety of
      schedules and either by intralumbar or intraventricular drug delivery.
      Notwithstanding that the treatment of leptomeningeal metastases is palliative,
      with an expected patient survival of 6 months, it often affords stabilization and
      protection from further neurologic deterioration in children with leptomeningeal
      metastases in whom death is usually a consequence of progressive systemic or
      parenchymal brain disease.

PMID- 7642889
TI  - Clobazam for intractable pediatric epilepsy.
AB  - We report our experience with add-on clobazam therapy over a 5-year period in 63
      children with refractory epilepsy. The mean duration of epilepsy was 6.7 years.
      Children were followed for 15 to 64 months. Of 63 children, 57 were
      developmentally delayed, and 54 had a symptomatic/cryptogenic epilepsy. Forty-one
      percent became either seizure free or had a greater than 90% reduction in seizure
      frequency. Seizure frequency was reduced 50% to 90% in another 24%. The average
      daily dose of clobazam was 0.8 mg/kg. Thirty-five percent had the medication
      withdrawn for persistent or unacceptable side effects or the development of
      tolerance (seven patients). Side effects included severe aggressive outbursts,
      hyperactivity, insomnia, and depression with suicidal ideation. Clobazam is a
      useful add-on medication for 65% of children with epilepsy. Clinical utility may
      be limited by behavioral side effects in some patients.

PMID- 7642890
TI  - Neurobehavioral and neurologic outcome in long-term survivors of posterior fossa
      brain tumors: role of age and perioperative factors.
AB  - We evaluated the neuropsychological and neurologic outcome of 15 long-term
      survivors of posterior fossa tumors who were treated between 1970 and 1984 with
      cranial irradiation (n = 15) and surgery (n = 14). The interval between diagnosis
      and evaluation ranged from 4 to 20 years (median = 10 years). Earlier age at
      diagnosis (< 6 years) was associated with an increased incidence of severe
      neurologic and neuropsychological sequelae. Hydrocephalus, obtundation, and tumor
      extension outside the vermis also were more prevalent in the younger group. Poor
      neurobehavioral outcomes in young children with posterior fossa tumors may be
      related to more aggressive tumor growth or complications of the initial therapy
      and not solely due to toxicity from craniospinal irradiation.

PMID- 7642891
TI  - Intraneural ganglion of the common peroneal nerve in a 4-year-old boy.
AB  - The case history of a 4-year-old boy with an intraneural ganglion of the common
      peroneal nerve is presented. These lesions are rare, more commonly affect males,
      and typically present with a painful foot-drop. A mass is often palpable adjacent
      to the neck of the fibula. Our patient has made a good recovery after surgery.

PMID- 7642892
TI  - Apparent life-threatening event: a neurologic perspective.
AB  - Of 46 infants who were investigated for apparent life-threatening events, central
      nervous system disorders were diagnosed in seven (15%). Convulsive disorders,
      intraventricular hemorrhage and hydrocephalus, absent corpus callosum, and
      development deficits were found. In four of the seven, no neurologic deficit was
      suspected before the event. Electroencephalographic studies (overnight in two)
      would have identified the disorder in all four. Electroencephalography is
      therefore a recommended routine procedure in investigation of apparent life
      threatening events. Central nervous system disorders should be routinely ruled
      out in cases of apparent life-threatening event, even in the absence of clinical
      clues.

PMID- 7642893
TI  - Glioneurocytoma: tumor with glial and neuronal differentiation.
AB  - We report two cases of low-grade glioma in which multiple cellular components,
      including cells with dense-core granules consistent with "neurocytes," were
      identified on electron microscopic studies. The first patient was an apparently
      normal boy until the onset of seizures at age 10 months. Initially, the seizures
      improved with phenobarbital treatment, but good seizure control was never
      achieved. Computed tomographic scan at age 23 months showed a calcified,
      nonenhancing left parietal mass. This tumor was composed of sheets of cells with
      clear cytoplasm and round to oval nuclei. Mucinous intercellular material stained
      positively with periodic acid-Schiff, mucicarmine, and alcian blue stains. Foci
      of calcification were evident. The second patient was a 13-year-old boy with a
      left parasagittal parieto-occipital mass who presented with a 4-month history of
      seizures and declining school performance. The tumor was composed of sheets of
      astrocytes with dark, hyperchromatic, pleomorphic nuclei in a fibrillary and
      microcystic background. The tumor contained the pleomorphism seen in the adult
      variant of pilocytic astrocytoma, as well as the microcystic component seen in
      the juvenile variety. Ultrastructurally in both cases, there were occasional
      tumor cells having round to oval nuclei with moderate amounts of cytoplasm
      containing 150- to 250-nm-diameter dense-core granules. These cells were admixed
      with the majority of tumor cells, which in case 1 had the ultrastructural
      features of astrocytes and oligodendrocytes and in case 2 had features of
      protoplasmic or pilocytic astrocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7642894
TI  - Southern Child Neurology Society meeting invited lecture. The saga of the septum
      pellucidum: a tale of unfunded clinical investigations.

PMID- 7642895
TI  - Medulloblastoma in an 8-year-old boy.

PMID- 7642896
TI  - Hypertensive encephalopathy in children: neuroimaging and treatment.

PMID- 7642897
TI  - Supraventricular tachycardia leading to stroke in childhood.

PMID- 7642898
TI  - Sulthiame revisited.

PMID- 7642899
TI  - Transient thalamic abnormality in association with seizure.

PMID- 7642900
TI  - Altered apnea threshold in a child with suspected brain death.

PMID- 7642901
TI  - Ganglioglioma of the pineal gland: clinical and radiographic response to
      stereotactic radiosurgical ablation.

PMID- 7642903
TI  - Cerebral infarction in a child with sickle cell trait.

PMID- 7642902
TI  - Giant axonal neuropathy in a child with insulin-dependent diabetes mellitus.

PMID- 7642904
TI  - Priority, rivalry, and peer review.

PMID- 7642905
TI  - Expert witness testimony: a time for self-regulation?

PMID- 7642906
TI  - Ergonomic disorders.

PMID- 7642907
TI  - Carpal tunnel surgery outcomes in workers: effect of workers' compensation
      status.
AB  - One hundred thirteen workers' compensation and 53 non-workers' compensation
      patients who had undergone open carpal tunnel release were queried about job
      status and the presence or absence of residual symptoms of numbness, pain, or
      nocturnal awakening an average of 42 months postoperatively. Thirty-nine non
      workers' compensation subjects were at their original jobs as compared to only 53
      workers' compensation subjects. Seventeen of the workers' compensation subjects
      were unemployed versus two non-workers' compensation subjects. These differences
      were significant. Of patients changing jobs, 39 workers' compensation subjects
      and 2 non-workers' compensation subjects attributed their job change to symptoms
      of carpal tunnel syndrome. Residual symptoms were significantly more common in
      workers' compensation compared to non-workers' compensation subjects, with 92 of
      the former and 26 of the latter subjects reporting some residual symptoms.

PMID- 7642908
TI  - Median nerve injury following YAG laser carpal tunnel release.

PMID- 7642909
TI  - A cadaveric study of the single-portal endoscopic carpal tunnel release.
AB  - Forty-three human cadavers underwent single-portal endoscopic carpal tunnel
      release using the Agee technique. Subsequent independent open dissection revealed
      complete release of all potentially compressing transverse structures in 19
      specimens and incomplete release in 24 specimens. There were 2 specimens with
      vascular injuries; one transection of a perforating branch of the palmar arch,
      and one transection of the ulnar artery at the entry portal. The 43 specimens
      were divided into three groups: group 1 (13 specimens) were released by the
      senior author in 1989; group 2 (13 specimens) were released by the senior author
      in 1992; and group 3 (17 specimens) were released by surgeons learning the
      technique under direct supervision of the senior author. Complete release was 5
      of 13 for group 1, 6 of 13 for group 2, and 8 of 17 for group 3. This study
      indicates that incomplete release is an inherent feature of this technique
      regardless of the surgeon's experience and despite blade redesign. The
      significance of incomplete release is unknown and must be determined in long-term
      clinical studies.

PMID- 7642910
TI  - A technique to quantitate motor recovery following nerve grafting.
AB  - Sixteen patients were evaluated retrospectively following grafting of an upper
      extremity peripheral nerve injury. In addition to the standard subjective muscle
      grading, the force of reinnervated muscle groups was quantitatively measured
      using force transducers, and reported relative to the contralateral side.
      Patients recovered a median motor grade of M3, which correlated to a 32% recovery
      of muscle force of the contralateral side. M3 and M4 motor grades encompassed a
      large range of actual muscle force: M3 correlated with a recovered force that
      ranged from 17% to 42%, M4 with a range of 66% to 79%. The percent force of motor
      recovery decreased significantly with longer delays to nerve grafting, even when
      controlling for the severity of the injury. Similarly, recovery of muscle force
      decreased when longer segments of nerve grafts were used. Testing the return of
      muscle strength after peripheral nerve injuries with a standardized objective
      system that compares function to the uninjured side enhances the sensitivity of
      evaluating nerve regeneration and provides a measurement system that can
      facilitate the comparison of different nerve repair techniques.

PMID- 7642911
TI  - Results of combined internal and external fixation for the treatment of severe AO
      C3 fractures of the distal radius.
AB  - Combined internal and external fixation for distal radius fractures has been
      previously reported, but the indications, technique, and results are not defined.
      This study reviews an experience with a specific surgical strategy for the
      treatment of a homogeneous population of AO-C3 fractures of the distal radius.
      The technique is composed of combined palmar and dorsal surgical approaches for
      open reduction and internal fixation of fracture fragments after neutralizing the
      wrist with a rigid external fixator. Thirteen fractures in 12 patients were
      followed an average of 27 months. Wrist motion averaged 60 degrees of flexion and
      45 degrees of extension. The injured extremities had a mean grip strength that
      was 83% of the uninjured side. Follow-up x-ray films showed a dorsal tilt of 1
      degree, radial inclination of 18 degrees, and radial length of 12 mm. Using the
      rating system of Green and O'Brien, the results were excellent or good in 10
      wrists. The results indicate that this surgical strategy, though technically
      demanding, can be successfully used in this specific subset of difficult to treat
      distal radius fractures.

PMID- 7642912
TI  - Flexible intramedullary nailing for metacarpal fractures.
AB  - A 5-year retrospective review of 83 patients with 98 metacarpal fractures was
      performed. Fractures of the thumb metacarpal were excluded. Ninety-six closed
      metacarpal fractures were reduced closed and fixed with flexible intramedullary
      fixation, using multiple 0.8-mm prebent rods. Two open metacarpal fractures were
      also fixed with this technique. Fractures amenable to flexible intramedullary
      fixation include short oblique and transverse fractures. Contraindications
      include long oblique and bicortical comminuted fractures. The average follow-up
      time was 9 months (range, 2 to 34 months) with 15 patients lost to follow-up
      examination. All fractures went on to heal. Three complications occurred: backing
      out of a rod in one case and bending of the rods after repeat trauma in two.
      There were no infections. Flexible intramedullary nailing of specific metacarpal
      fractures affords excellent results with a low complication rate. Proper
      selection of fractures and good surgical technique are necessary to avoid
      complications.

PMID- 7642913
TI  - Single third-toe transfer in hand reconstruction.
AB  - Eighteen third-toe transfers to the hand were performed from 1984 to 1993 in 15
      patients. These patients had multiple amputations, and follow-up ranged from 5 to
      78 months with an average of 27 months. Single third-toe-to-hand transfer was
      elected when (1) the second toe was not available or not suitable for transfer,
      (2) the second toe was located in the same foot where the great toe had been
      transferred to the thumb and the second toe was, therefore, spared for gait, or
      (3) the third toe was a better size match.

PMID- 7642914
TI  - Reverse digital artery neurovascular cross-finger flap.
AB  - Soft tissue loss with digital nerve defect in the finger was reconstructed with
      the reverse digital artery neurovascular cross-finger flap in two cases with
      favorable results. The flap harvested from the lateral side of the proximal
      phalanx of the neighboring healthy finger is nourished by a distally based
      digital artery. The flap contained a segment of digital nerve dorsal branch,
      which is used to bridge the nerve gap in the wound while the flap is used to
      reconstruct the soft tissue defect concomitantly. The reverse digital artery
      neurovascular cross-finger flap seems to be a useful addition to the options for
      complicated finger damage involving soft tissue loss and nerve defect.

PMID- 7642915
TI  - Salvage of ring degloving injury with wraparound flap from adjacent mutilated
      digit.

PMID- 7642916
TI  - Radial artery occlusion by a paradoxical embolism: a case report.

PMID- 7642917
TI  - Double free-muscle transfer to restore prehension following complete brachial
      plexus avulsion.
AB  - Restoration of finger flexion and extension as well as elbow flexion and
      extension with a double free-muscle and multiple nerve transfers following
      complete avulsion of the brachial plexus (nerve roots C5 to T1) is reported. The
      procedure combines (1) free-muscle transfer with reinnervation by the spinal
      accessory nerve to achieve elbow flexion and finger extension, (2) free-muscle
      transfer with reinnervation by the fifth and sixth intercostal nerves to restore
      finger flexion, (3) third and fourth intercostal motor nerve transfer to the
      triceps brachi to extend and stabilize the elbow, (4) nerve transfer of the
      supraclavicular nerve or nerve transfer of the sensory rami of the intercostal
      nerves to the median nerve to restore hand sensibility, and (5) glenohumeral
      arthrodesis. Seven of 10 patients recovered elbow function and finger flexion and
      extension. Five patients reported use of their hand in activities of daily
      living.

PMID- 7642918
TI  - Two-stage reconstruction for the hypoplastic thumb.
AB  - A 2-year-old boy with grade 3 hypoplastic thumb (Blauth's classification)
      underwent reconstruction in two stages. Stage 1 was an abductor digiti quinti
      musculocutaneous flap, first web space widening, and insertion of a silicone rod
      to prepare for a flexor pollicis longus transfer. Stage 2 (6 months later) was a
      vascularized second toe proximal interphalangeal joint transfer for
      carpometacarpal joint replacement, plus tendon transfers for thumb flexion,
      extension, and adduction. Three years following the procedures, the thumb had an
      open physis by x-ray film and was functioning well. Pollicization is the
      traditional procedure for this degree of thumb hypoplasia, but the two-stage
      reconstruction is an alternative for patients in cultures where the presence of
      five fingers is important.

PMID- 7642919
TI  - Preliminary soft tissue distraction in congenital forearm deficiency.
AB  - Four patients (five limbs) were treated with preliminary soft tissue distraction
      using an Orthofix external distractor. The patient's ages ranged from 6 months to
      14 years. Forearm deficiencies treated included partial absence of the radius
      (one patient), radial aplasia (two patients, three limbs), and partial absence of
      the ulna (one patient). Soft tissue distraction (mean, 55 days) was continued in
      radial deficiency until the hand could be passively centralized without residual
      radial deviation, allowing centralization to be accomplished through a single mid
      dorsal incision. Mean measurement of distraction for the radial deficiencies was
      1 cm. In the ulnar deficiency, soft tissue distraction was carried out until the
      cut radius was distal to the partially absent ulna (98 days) allowing for the
      creation of a one-bone forearm using the entire radius. Distraction (1 mm/day)
      was done by the children's parents with no distractor removed because of patient
      intolerance. All radial deficiency limbs remained centralized at a mean followup
      period of 14 months.

PMID- 7642920
TI  - Adolescent trigger finger secondary to post-traumatic chronic calcific
      tendinitis.

PMID- 7642921
TI  - Classification and surgical treatment of the thumb-in-palm deformity in cerebral
      palsy and spastic paralysis.
AB  - Over a 20-year period, 59 children with spasticity mainly due to cerebral palsy
      underwent surgery for correction of a thumb-in-palm deformity. A classification
      of the deformity based on the functional anatomy of the thumb divided the problem
      into four different types. A retrospective analysis of the results has shown the
      classification to be helpful in selecting a surgical option for treatment. In
      addition, the classification helps to keep accurate records, predict patient
      progress, and coordinate postoperative treatment.

PMID- 7642922
TI  - Giant cell tumor of the distal radius.
AB  - We compared the outcome of patients with giant cell tumor of the distal radius
      treated by curettage/cryosurgery and en bloc resection, evaluating oncologic
      success, functional results, and complications. Thirty consecutive cases of giant
      cell tumor of the distal radius were treated at our institution between 1958 and
      1988. Twenty-six patients were available for follow-up examination, with a
      minimum follow-up period of 3 years and median follow-up period of 9 years.
      Primary curettage/cryosurgery had a local recurrence in 3 of 12, and repeat
      curettage/cryosurgery achieved local control in in 16 of 18 primary and recurrent
      cases. The major complications in this group included skin necrosis, transient
      nerve palsies, and fragmentation with carpal collapse. An average of 60% of
      contralateral range of wrist motion was preserved. Ten patients underwent en bloc
      excision and arthrodesis for either primary or recurrent tumor; none developed
      local recurrence. The main complication in this group was failure of internal
      fixation and non-union at the graft-radius junction. Resultant strength and
      function were similar in both groups. Intralesional excision with adjunctive
      cryosurgery is an effective alternative to en bloc excision with the advantage of
      preserving the distal radius and wrist joint function, but with a notable
      complication rate. En bloc excision with arthrodesis is more suitable for
      extensive local disease with poor residual bone stock and as salvage for failed
      intralesional excision.

PMID- 7642923
TI  - Ewing's sarcoma of the hand: magnetic resonance images and treatment.
AB  - Two cases of Ewing's sarcoma of the hand were treated by preoperative
      chemotherapy and radiation therapy to decrease tumor volume. Magnetic resonance
      images were useful in showing the soft tissue mass and in estimating the effect
      of the chemotherapy. The results of surgery were satisfactory with this treatment
      regimen.

PMID- 7642924
TI  - Swanson silicone finger joint implants: a review of the literature regarding long
      term complications.
AB  - A review of the English-language literature pertaining to complications
      associated with Swanson Silastic (Dow Corning, Midland, MI) finger implants was
      performed. The review focused on seven broad categories of complications:
      synovitis, lymphadenopathy, bone change, implant fracture, implant loosening,
      infection, and implant removal. Outcome data on 15,556 small joint implants were
      identified in 70 pertinent articles. The prevalence rates of complications
      associated with finger implants were all very low. Implant fracture and bone
      changes occurred in 2% and 4% (respectively) of finger implants. Each of the
      other complications developed in 1% or less of implants, including particulate
      synovitis (0.06% of implants). Particle-wear lymphadenopathy was reported in
      0.08% of implants. The literature review identified no reports of immunologic
      reactions, connective tissue disease, or other systemic effects associated with
      the use of Swanson finger implants.

PMID- 7642925
TI  - Correlation of alpha-smooth muscle actin expression and contraction in
      Dupuytren's disease fibroblasts.
AB  - We studied 11 nodules from patients with Dupuytren's contracture to determine
      whether alpha-smooth muscle actin expression in Dupuytren's fibroblasts is
      related to the generation of contractile force. Tissue was placed into explant
      culture and fibroblast strains were obtained. The mean percent of cultured
      Dupuytren's fibroblasts expressing alpha-smooth muscle actin, as determined by
      immunofluorescence, was 14 +/- 8 and ranged from 1% to 26%. The ability of
      Dupuytren's fibroblasts to generate contractile force was determined by using a
      previously described collagen lattice contraction assay. We observed a
      significant positive correlation between the expression of alpha-smooth muscle
      actin and the generation of contractile force in cell strains of Dupuytren's
      fibroblasts. In addition, six fibroblast strains from palmar fascia of
      individuals undergoing carpal tunnel release were examined. In six strains of
      palmar fibroblasts the mean percent of cells expressing alpha-smooth muscle actin
      was 5 +/- 3 and ranged from 1% to 9%. Six Dupuytren's fibroblast strains, in
      which more than 15% of the cells expressed alpha-smooth muscle actin, were
      significantly more contractile than the palmar fibroblasts. These results suggest
      that Dupuytren's fibroblasts can acquire smooth muscle characteristics and that
      the acquisition of a smooth muscle-like phenotype correlates with increased
      contractility.

PMID- 7642926
TI  - Detection of a 0.5-mm-thick thorn using ultrasound: a case report.

PMID- 7642927
TI  - The role of bone scintigraphy in diagnosing reflex sympathetic dystrophy.
AB  - Three-phase bone scintigraphy is used often to diagnose reflex sympathetic
      dystrophy of the hand. This study presents an analysis of the literature relating
      three-phase bone scanning to reflex sympathetic dystrophy in the upper extremity.
      The data show a wide variability in scintigraphic accuracy in patients with
      clinically obvious reflex sympathetic dystrophy. The results of bone scintigraphy
      correlate best with the clinical diagnosis of reflex sympathetic dystrophy within
      the first 20-26 weeks of onset. Even then, the sensitivity in the most recent
      series approximates 50%. After 26 weeks, there is a poor correlation between
      three-phase bone scanning and reflex sympathetic dystrophy. Consequently, three
      phase bone scintigraphy should not be used as a major criterion in diagnosing
      reflex sympathetic dystrophy. The diagnosis of reflex sympathetic dystrophy
      remains a clinical diagnosis made by an experienced hand surgeon.

PMID- 7642928
TI  - Magnetic resonance imaging findings in Secretan's disease.
AB  - Secretan's disease is defined as hyperplastic, recurring hard edema of the dorsal
      aspect of the hand. Its etiology, pathology and treatment are unclear. Magnetic
      resonance images and surgical findings are presented in three patients who fit
      the clinical findings of Secretan's disease. Magnetic resonance imaging scans
      with both T-1 weighted and T-2 weighted images showed soft tissue and tendon
      edema in combination with diffuse peritendonous fibrosis extending to the fascia
      of the dorsal interosseous muscles.

PMID- 7642929
TI  - Effect of cyclic tension on lacerated flexor tendons in vitro.
AB  - The effect of tension on tendon healing was evaluated in vitro using cyclic
      tension and no tension groups of chicken flexor digitorum profundus tendons and
      histologic and immunohistologic techniques. A Vitrodyne force-loading machine was
      used for application of cyclic tension on partially lacerated chicken flexor
      tendons in culture media. Laceration sites under cyclic tension after 14 days
      were covered by newly proliferated fibroblasts, aligned in the direction of
      tension. This new growth was much thicker than that seen in the no tension group
      at the same time interval. Procollagen synthetic activity began at 3 days of
      culture in both groups. At 21 days, newly formed fibroblasts in the cyclic
      tension group were stained positive more strongly at the surface layer than in
      the deeper layers. In the no tension group, the staining was primarily in the
      surface layer. Cyclic tension stimulated the intrinsic response of lacerated
      flexor tendons significantly more than no tension did by enhancing proliferation
      and migration of fibroblasts, as well as stimulating collagen synthesis.

PMID- 7642931
TI  - Intratendinous rupture of the flexor digitorum profundus tendon in zones II and
      III.
AB  - Spontaneous flexor tendon ruptures are rare. Thirteen patients who had
      spontaneous intratendinous rupture of the flexor digitorum profundus tendon are
      described. Twelve of the ruptures occurred in zone III at the level of the
      lumbrical origin, and one occurred in zone II distal to the A2 pulley. All
      patients were involved in an activity that required flexion against resistance.
      Time from injury to treatment averaged 5 weeks. Surgical exploration and
      subsequent histologic evaluation did not show any pathologic condition to explain
      the rupture. Surgical treatment was dependent primarily on time from rupture and
      on the location of the injury; seven patients had direct repair, five had tendon
      grafting, and one was treated with tendon transfer. Postoperative follow-up time
      averaged 36 months. All patients regained good-to-excellent active range of
      motion and returned to work. Patients who had early direct repair of the tendon
      had better functional results than those who were treated with tendon grafting or
      tendon transfer.

PMID- 7642930
TI  - Traumatic rupture of the extensor tendons at the musculotendinous junction.
AB  - Ten cases of closed extensor tendon rupture at the musculotendinous junction are
      reported. In five patients the rupture occurred at work, and in five during
      athletic activities. In each instance, indirect tendon injury resulted from a
      strong stretching force applied to a contracting muscle. In one case, rupture of
      the extensor pollicis longus tendon occurred proximal to the extensor
      retinaculum. In eight cases of complete tendon rupture direct repair was
      impossible. Of these eight patients, five were treated by side-to-side juncture
      and three by tendon transfer. Two patients with incomplete rupture were treated
      by splinting. All patients improved after treatment.

PMID- 7642932
TI  - A functional anomalous deep flexor tendon to the long and ring fingers: a case
      report.

PMID- 7642933
TI  - Irreducible dislocation of the interphalangeal joint of the thumb due to sesamoid
      bone interposition: a case report.

PMID- 7642934
TI  - Irreducible thumb interphalangeal joint dislocation due to a sesamoid and palmar
      plate: a case report.

PMID- 7642936
TI  - The pronator quadratus: a distinct forearm space?
AB  - The pronator quadratus sign is associated with fractures of the distal radius and
      ulna and is believed to be due to accumulation of fluid within the pronator
      quadratus muscle. This anatomic study based on dye injection and x-ray film
      examination shows that the pronator quadratus occupies a distinct forearm space
      without intramuscular communication.

PMID- 7642935
TI  - The flexor digitorum longus: an anatomic and microscopic study for use as a
      tendon graft.
AB  - Recent experimental studies have shown that intrasynovial donor tendons have the
      capacity to heal with minimal alteration in the gliding surface when grafted to
      an intrasynovial location. In order to evaluate the flexor digitorum longus of
      the foot as a potential matched donor tendon for use in flexor tendon grafting,
      we dissected 15 feet (75 toes) and 10 hands (50 fingers) to determine the
      intrasynovial lengths of the flexor digitorum longus and flexor digitorum
      profundus and to determine a method of tendon graft harvest. Specimens were taken
      from the intrasynovial portion of each tendon for evaluation by light and
      electron microscopy. The intrasynovial tendons of the hand and foot were similar
      in vascularity, cellularity, gliding surface, and ultrastructure. The flexor
      digitorum longus tendon of the foot was a mean length of 12 cm to the area of
      tendon confluence in the midfoot, which will usually provide enough tendon length
      for grafting from the distal phalanx to the palm of the hand. Because of the
      difference in length of the synovial sheaths of the fingers and toes, some
      extrasynovial tendon will be transferred to the synovial space when a flexor
      digitorum longus tendon is used.

PMID- 7642937
TI  - Synergistic necrotizing cellulitis in the hand of a renal dialysis patient: a
      case report.

PMID- 7642938
TI  - Treatment of fingernail deformities secondary to ganglions of the distal
      interphalangeal joint.

PMID- 7642939
TI  - Scaphocapitate arthrodesis for the treatment of Kienbock's disease.
AB  - Eleven consecutive patients, ten men and one woman (median age, 26 years)
      presenting with Kienbock's disease, were treated with scaphocapitate arthrodesis.
      Ten patients had grade III, and one had grade II disease by Lichtman
      classification. The average follow-up period was 36 months (minimum, 1 year). The
      lunate was left in situ and scaphocapitate arthrodesis was performed with two lag
      screws and corticocancellous bone graft. The ulnar variance of the affected wrist
      was negative (-2.23 mm) and significantly different from the unaffected side. Ten
      patients had complete pain relief and one had persistent pain. Nine returned to
      their previous vocations.

PMID- 7642940
TI  - X-ray evaluation of the true neutral position of the wrist: the groove for
      extensor carpi ulnaris as a landmark.

PMID- 7642941
TI  - Therapeutic value of repetitive motion: work fitness hypothesis, a response to
      Mackinnon and Novak.

PMID- 7642942
TI  - Silicone implants and titanium grommets.

PMID- 7642943
TI  - Subcutaneous mercury granulomas.

PMID- 7642944
TI  - Cryptococcal infection.

PMID- 7642945
TI  - The host response to silicone elastomer implants for small joint arthroplasty.

PMID- 7642946
TI  - Development of hand surgery certification in the United States.

PMID- 7642947
TI  - Curriculum for training in hand surgery: report of the Education Committee of the
      IFSSH. International Federation of Societies for Surgery of the Hand.

PMID- 7642948
TI  - Forty years of microsurgery: what's next?

PMID- 7642949
TI  - History of flexor tendon repair.

PMID- 7642950
TI  - Repetition strain injury: the Australian experience--1992 update.

PMID- 7642951
TI  - Factitious injuries of the upper extremity.

PMID- 7642952
TI  - War wounds of the hand revisited.

PMID- 7642953
TI  - The treatment of war injuries of the brachial plexus.

PMID- 7642954
TI  - Tennis: dynamics of racket-grip interaction.

PMID- 7642955
TI  - A new technique to correct carpal instability with scaphoid rotary subluxation: a
      preliminary report.

PMID- 7642956
TI  - "Bouquet" osteosynthesis in metacarpal neck fractures: a series of 66 patients.

PMID- 7642957
TI  - Treatment of long-standing dislocation of the radial head in neglected Monteggia
      fractures.

PMID- 7642958
TI  - Long-term results of proximal interphalangeal joint resection arthroplasties with
      a silicone implant.

PMID- 7642959
TI  - Intra-articular injection of thiotepa in the treatment of rheumatoid arthritis of
      the digital joints.

PMID- 7642960
TI  - High-sensitivity diagnosis of AA amyloidosis using Congo red and
      immunohistochemistry detects missed amyloid deposits.
AB  - Biopsy diagnosis of early amyloid-A (AA) amyloidosis has often been difficult.
      Examination of 57 consecutive biopsy specimens from 42 patients with inflammatory
      pediatric diseases permitted comparison of the precision of biopsy amyloid
      diagnosis in six different laboratories (labs), which applied the following
      methods: Congo red alone (four unspecialized labs combined as Lab 1), Congo red
      and electron microscopy (Lab 2), or Congo red and immunohistochemistry using
      monoclonal antibodies (Lab 3). Lab 3 reexamined the diagnoses made by Lab 1 and
      Lab 2. Of the 42 patients, 17 patients with 32 biopsies were selected for this
      study based on the presence of amyloid in at least one biopsy. Whereas massive or
      no amyloid was concordantly recognized by all labs in 18 biopsies from nine
      patients, discordance was demonstrated in 14 biopsies from eight patients.
      Comparison of Labs 1-3 revealed amyloid in 12 rectal and 18 renal biopsies
      evaluated by Lab 3, whereas Lab 2 missed amyloid in two of 18 renal biopsies and
      Lab 1 missed amyloid in 11 of 12 rectal biopsies. Most amyloid was missed when
      only minute amounts of amyloid were present. Had our technique (Lab 3) been
      available at the time of biopsy, amyloid could have been diagnosed years earlier,
      thereby sparing the patient further biopsies and allowing initiation of earlier
      treatment before organ damage could occur.

PMID- 7642961
TI  - Possibilities of false immunocytochemical results generated by the use of
      monoclonal antibodies: the example of the anti-proinsulin antibody.
AB  - The immunocytochemical application of a monoclonal antibody (MAb) against the Arg
      Arg region at the junction of the C-peptide and the insulin beta-chain of the
      human proinsulin molecule on rat pancreatic tissue resulted in positive
      immunogold labeling over the insulin- as well as the glucagon-secreting cells. In
      the insulin cells, the Golgi cisternae and the immature clathrin-coated granules
      were intensely labeled, and in the glucagon cells all the granules were labeled.
      Control experiments using the anti-proinsulin MAb adsorbed with proinsulin,
      insulin, and glucagon have confirmed the crossreactivity of this proinsulin
      antibody with glucagon. Furthermore, the anti-proinsulin MAb appears to
      crossreact not only with rat but also with human glucagon and with bovine and
      porcine insulin and glucagon. Examination of the amino acid sequences of
      proinsulin and proglucagon has shown that both molecules display this Arg-Arg
      dipeptide sequence, which could explain the labeling obtained on both cell types.
      In addition, other propeptides also display such a sequence and, indeed, positive
      cells were detected in rat pituitary. These results demonstrate that by
      immunocytochemistry this MAb, although providing very specific results, reveals
      non-related molecules. This is due to the fact that these molecules exhibit
      similar short determinants. MAbs raised against very short amino acid sequences
      can reveal this determinant in various molecules, generating false-positive
      results.

PMID- 7642962
TI  - Amount variability of total and individual Ag-NOR proteins in cells stimulated to
      proliferate.
AB  - Ribosomal genes are associated with a subset of acidic proteins called Ag-NOR
      proteins. The amount of nucleolar Ag-NOR proteins varies, depending on nucleolar
      activity and/or cell proliferation. To understand the linkage between the amount
      of Ag-NOR proteins, ribosome biogenesis, and cell proliferation, we investigated
      the variability of Ag-NOR proteins in rRNA-stimulated cells maintained in G1 and
      in rRNA-stimulated cells entering the mitotic cycle. Rat hepatocytes were
      stimulated with cortisol for rRNA synthesis (1, 4, and 8 hr) and the cell cycle
      was induced by hepatectomy in regenerating hepatocytes (3-21 hr). In non
      stimulated hepatocytes, nucleolin and protein B23 were the two major Ag-NOR
      proteins, corresponding to 70% of total Ag-NOR staining. In hepatocytes
      stimulated for rRNA synthesis in G1, the amount of Ag-NOR proteins was only
      slightly increased, whereas in cycle-stimulated cells it was increased 3.04-fold.
      This is the consequence of a differential increase of the major Ag-NOR proteins
      that appears earlier and is proportionally more important for nucleolin (3.5
      fold) than for protein B23 (twofold) and also for the increase of several minor
      Ag-NOR proteins. We conclude that, in dividing cells, the mean value of the Ag
      NOR proteins measured reflects the percentage of cells in the different phases.
      This could explain why the amount of Ag-NOR proteins can be used as a marker of
      cell proliferation.

PMID- 7642964
TI  - Effect of light stimulation on the cytochemical localization of cytochrome C
      oxidase in photoreceptor cells of cichlid fish.
AB  - Cytochrome oxidase activity was evaluated cytochemically in rod photoreceptor
      cells in the retina of the cichlid fish Oreochromis mossambicus after different
      stimulation protocols. The enzyme activity was assessed semiquantitatively by
      estimating the volume ratio of mitochondria classified according to the intensity
      of enzyme reactivity. Dark adaptation for 5 hr induced an increase of cytochrome
      oxidase activity both in vivo and in vitro, i.e., in isolated retinas. Short-term
      illumination (1 hr) of isolated retinas adapted previously in vivo to darkness
      caused a significant decrease of enzyme activity, whereas short-term darkening
      after in vivo light adaptation had no effect. Chemical stimulation for 15 min
      with increased K+ concentration (20 mM) reduced the enzyme activity, i.e.,
      chemical depolarization did not have the same effect as depolarization induced by
      darkening. Significant changes in cytochrome oxidase activity were apparent
      within 1 hr of stimulation, so that this method for analysis of neuronal activity
      can be applied even in short-term experiments.

PMID- 7642963
TI  - Expression of plasminogen activator-inhibitor-1 (PAI-1) during cellular
      remodeling in proliferative glomerulonephritis in the rat.
AB  - Pericellular proteolysis involves the plasminogen activator/plasmin system and
      plays an important role in cell remodeling involving cell migration and
      extracellular matrix turnover. Studies in this laboratory have previously
      characterized a model of proliferative glomerulonephritis induced by Habu snake
      venom (HSV) in the rat that involves cell migration, proliferation, and
      extracellular matrix accumulation. Because plasminogen activator-inhibitor-1 (PAI
      1) has been used as a marker for cell migration as well as matrix accumulation,
      we were interested in examining the temporal and spatial expression and cellular
      sources of PAI-1 mRNA and translated protein over the course of HSV-induced
      proliferative glomerulonephritis. The results showed a highly localized and
      progressive expression of PAI-1 mRNA and translated protein by in situ
      hybridization and immunohistochemistry at the margins and periphery of glomerular
      lesions 8 and 24 hr after HSV. The expression of PAI-1 in glomerular lesions
      localized to the same sites as mesangial cell marker proteins, desmin and Thy
      1.1, indicating that mesangial cells synthesize this important regulator
      proteolysis. Few cells expressed PAI-1 in the central aspects of glomerular
      lesions at later time intervals (48 and 72 hr) when cell proliferation and
      expression of extracellular matrix (fibronectin protein and mRNA) were maximal.
      Therefore, the expression of PAI-1 in this model was associated more with early
      events related to cell migration than with proliferation or extracellular matrix
      synthesis. These observations support the hypothesis that the plasminogen
      activator/plasmin system is involved in cell migration in early remodeling during
      glomerular disease.

PMID- 7642965
TI  - Ultrastructural localization of alkaline phosphatase activity in human eccrine
      and apocrine sweat glands.
AB  - Alkaline phosphatase (ALP) is a membrane-bound enzyme that catalyzes the
      hydrolysis of inorganic and organic monophosphate esters at alkaline pH. Although
      the functions of ALP are poorly understood, it is believed to be involved in
      membrane transport. Because little is known about the functions and distribution
      of ALP in the sweat glands, we studied the localization of ALP in human sweat
      glands with light and electron microscopic enzyme cytochemistry. In eccrine sweat
      glands, ALP was restricted to the cell membranes of intercellular canaliculi.
      Luminal cell membranes of secretory cells that are in continuity with
      intercellular canaliculi did not show ALP activity. These results suggest that
      ALP participates in the production of primary sweat at intercellular canaliculi.
      In apocrine sweat glands, basal cell membranes of secretory cells and
      myoepithelial cell membranes that were in apposition with each other showed ALP
      activity, where as no activity was seen in eccrine sweat glands. These
      differences in the distribution of ALP in myoepithelial cells between eccrine and
      apocrine sweat glands might be related to the functional differences of these
      sweat glands. ALP histochemistry could help to diagnose and to determine the
      direction of differentiation in sweat gland tumors.

PMID- 7642966
TI  - Cytotrophoblast cells: a barrier to maternofetal transmission of passive
      immunity.
AB  - The human fetus receives passive immunity via the chorioallantoic placenta in the
      form of maternal immunoglobulin G (IgG) class antibodies. This provides
      protection against pathogens at a time when the fetus is immunologically naive.
      We localized endogenous human IgG using confocal laser scanning fluorescence
      microscopy and immunoelectron microscopy of frozen sections of chorionic villi
      from early and late gestation. With confocal microscopy we also investigated the
      distribution of a receptor for IgG (Fc gamma RIII; CD16) that is typically
      expressed on the surface of human leukocytes. Endogenous IgG was present in the
      syncytiotrophoblast that surrounds chorionic villi but underlying cytotrophoblast
      cells were devoid of endogenous antibody. Fc gamma RIII immunoreactivity was
      confined to the syncytiotrophoblast and was also absent from cytotrophoblast
      cells. We propose that cytotrophoblast cells present a barrier to the
      transmission of maternally derived IgG across the human placenta. This accounts
      for the paradox that there are low levels of transport in the first trimester
      when the syncytiotrophoblast is known to express receptors for IgG.
      Cytotrophoblast cells form an almost complete epithelial layer underlying the
      syncytiotrophoblast at this stage of gestation, but this becomes discontinuous as
      the placenta matures, thus removing the cellular impediment to IgG transmission.

PMID- 7642967
TI  - Expression of Gal beta 1,4GlcNAc alpha 2,6-sialyltransferase and alpha 2,6-linked
      sialoglycoconjugates in normal human and rat tissues.
AB  - We performed histochemical studies on normal human and rat tissues using anti-Gal
      beta 1,4GlcNAc alpha 2,6-sialyltransferase (alpha 2,6-ST) antibody and Sambucus
      nigra agglutinin (SNA). alpha 2,6-ST and its products were detected in almost all
      tissues examined. However, the staining intensities varied significantly with
      different cell types. Some secretory epithelial cells, such as hepatocytes and
      choroid plexus cells, were vividly stained with either anti-alpha 2,6-ST or SNA.
      In several cell types the intensity of alpha 2,6-ST staining did not always
      correlate with SNA stainability. Neurons and gastrointestinal epithelia were
      rarely stained with SNA, even though they were positive for alpha 2,6-ST. In
      contrast, the endothelial cells of blood vessels strongly reacted with SNA
      despite their weak alpha 2,6-ST expression. The precise physiological roles
      played by alpha 2,6-linked sialylated glycoconjugates have been unclear. However,
      the findings described here lend further support to their important role in cell
      growth and differentiation, since immature blood cells, including megakaryocytes
      in bone marrow, were intensely stained with anti-alpha 2,6-ST and SNA, and SNA
      reaction products were primarily observed in the basal and suprabasal layers of
      the stratified epithelia rather than in the more differentiated upper layers. In
      view of the vivid reactivity of anti-alpha 2,6-ST in the decidual cells of the
      placenta, it seems likely that alpha 2,6-ST expression is under hormonal control.

PMID- 7642968
TI  - The role of Langerhans islets in exocrine pancreatic cancer.

PMID- 7642969
TI  - Recovery of the pancreas after acute pancreatitis is not necessarily complete.
AB  - In 38 patients, exocrine pancreatic function was tested by means of the secretin
      pancreozymin test (SPT) and pancreatic duct system with endoscopic retrograde
      cholangiopancreatography (ERCP) 34 +/- 36 mo (mean +/- SD, range 1-156 mo)
      following acute pancreatitis. SPT and ERCP results were both normal in 19 (50%).
      They were both abnormal in four (11%) patients (group 1). Fourteen (37%) patients
      with normal SPT had abnormal ERCP test results (group 2), and one (3%) patient
      with normal ERCP had abnormal SPT (group 3). All patients except one of group 2
      could be followed up within a mean observation time of 105 +/- 46 mo (range 24
      168 mo): Chronic pancreatitis developed in all four patients of group 1, in one
      patient of group 2, and in the single patient of group 3, and suspected chronic
      pancreatitis in another patient of group 2. Eleven of the remaining 12 patients
      with abnormal ERCP results, but normal exocrine pancreatic function (group 2),
      showed no signs or symptoms of acute or chronic pancreatitis. It is concluded
      that (1) recovery to normal does not necessarily occur after acute pancreatitis,
      (2) progression to chronic pancreatitis is possible at a considerable percentage,
      and (3) duct changes demonstrated by ERCP may persist without any later signs and
      symptoms of acute or chronic pancreatitis.

PMID- 7642971
TI  - Expression of p53 protein in pancreatic adenocarcinoma. Relationship to cigaret
      smoking.
AB  - We studied the expression of p53 gene product in pancreatic adenocarcinomas of
      the usual ductal type to determine its relationship to cigarette smoking and its
      usefulness as an independent prognostic indicator. Twenty-six resection specimens
      of pancreatic adenocarcinoma were examined by immunohistochemistry using an
      antigen retrieval solution and monoclonal PAb1801 and polyclonal CM1 antibodies
      on paraffin-embedded material. Specific nuclear p53 expression for both PAb1801
      and CM1 was identified in seven cases (27%). In all cases immunoreaction was
      confined to neoplastic cells. Three of four (75%) tumors from patients who had
      never smoked showed immunoreaction, whereas only three of 14 (21%) tumors from
      smokers showed positive staining. Cases with positive staining had shorter mean
      survival (6.3 mo) than cases that failed to stain (9.8 mo), but the difference
      was not statistically significant in this small study. There was no statistically
      significant association between p53 immunoreactivity and other clinicopathologic
      parameters. Our findings indicate that abnormalities of p53 gene in pancreatic
      adenocarcinomas may not be directly related to cigarette smoking. Those patients
      who survived the longest tended to have tumors negative for p53 immunostaining.
      p53 immunoreaction may be a useful feature in distinguishing adenocarcinoma from
      chronic pancreatitis in small biopsies.

PMID- 7642970
TI  - Cerulein-induced acute pancreatitis diminished vitamin E concentration in plasma
      and increased in the pancreas.
AB  - Redistribution of vitamin E in the rat body was studied during acute pancreatitis
      induced by two intraperitoneal doses of cerulein 40 micrograms/kg of body weight
      at 1-hr intervals. Hyperamylasemia (2064 +/- 521 vs 6419 +/- 129 U/dL) and
      pancreatic edema (pancreatic water content, 71 +/- 1.2% vs 78 +/- 2%) were
      observed. In this model the increased level of lipid soluble fluorophore was also
      observed (274 +/- 18 vs 120 +/- 9.0 relative fluorescence per g dry wt). Parallel
      with these changes was a decrease in the level of vitamin E in the serum and an
      increase in the pancreas. The concentration of vitamin E in the pancreas after 6
      h was 162 +/- 8.5 ng/mg dry mass vs 128.1 +/- 6.1 ng/mg dry mass in control
      animals. The effect of heparin on vitamin E redistribution induced by acute
      pancreatitis was also investigated. It was found that heparin at a dose of 100
      U/kg body mass prevents the drop of the vitamin E level in the serum as well as
      the increases in the concentration in the pancreas tissue. It was concluded that
      acute pancreatitis induced redistribution of vitamin E in the rat body. Moreover,
      we studied the effects of heparin treatment on oxidative stress in the pancreas
      tissue. Acute pancreatitis caused an increase in lipofuscin accumulation, and a
      decrease in protein sulfhydryl groups in citrate synthetase (CS) and in malate
      dehydrogenase (MDH) activity. Heparin treatment that protected vitamin E
      accumulation in the pancreas tissue did not influence the changes in the level of
      lipofuscin and proteins sulfhydryl.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7642972
TI  - Exocrine pancreatic insufficiency after allogeneic bone marrow transplantation.
AB  - Several reports suggest a relationship between bone marrow transplantation and
      pancreatic damage. The authors describe two patients with pancreatic
      insufficiency after bone marrow transplantation. The first patient had weight
      loss arising from steatorrhea secondary to severe pancreatic insufficiency
      (lipase output result <3% of normal) due to pancreatic atrophy. The second
      patient had steatorrhea secondary to intestinal bacterial overgrowth, but
      moderate pancreatic insufficiency was present (results of trypsin and lipase
      outputs were 50 and 30% of normal). Before the diagnosis of pancreatic
      insufficiency, both patients had acute graft vs host disease and the second
      patient had chronic graft vs host disease. We conclude that graft vs host disease
      after bone marrow transplantation may damage the pancreas. Patients with
      persistent malabsorption after bone marrow transplantation should be tested for
      exocrine pancreatic insufficiency.

PMID- 7642973
TI  - Staging of carcinoma of the pancreas and ampulla of Vater. Tumor (T), lymph node
      (N), and distant metastasis (M) as prognostic factors.
AB  - Between 1984 and 1987, 472 Norwegian patients with histologically or
      cytologically verified carcinoma of the pancreas (N = 442) and ampulla of Vater
      (N = 30) were accrued and TNM staged according to UICC. The influence of the T,
      N, and M categories on long-term survival was evaluated. The T1a and T1b tumors
      of stage I pancreatic carcinoma had a comparable survival (p = 0.68-0.95). A
      higher T category (T1-T3) predicted a more dismal prognosis (p = 0.000). The T1
      and T2 carcinomas of the ampulla of Vater had a comparable favorable prognosis,
      and the T3 and T4 tumors had a comparable unfavorable prognosis. The N1 vs N0 (p
      = 0.000-0.01) and M1 vs M0 categories (p = 0.00-0.003) predicted a more dismal
      prognosis for both pancreatic and ampullary carcinoma. By logistic regression
      analyses, pancreatic tumor extension into peripancreatic fat or nerves and
      invasion of ampullary carcinomas into duodenal wall, unfavorably influenced the
      N1 category (p = 0.000-0.04) and tumor diameter influenced the M1 category (p =
      0.002-0.04) both for pancreatic and ampullary carcinoma. The T, N, and M
      categories all independently influenced survival of pancreatic carcinoma (p =
      0.000-0.003). Only the N category (p = 0.01) influenced the prognosis of
      ampullary carcinomas.

PMID- 7642974
TI  - Intraduodenal cholecystokinin octapeptide (CCK-8) can stimulate pancreatic
      secretion in the calf.
AB  - The effect of CCK-8 administered into the duodenal lumen and into the systemic
      blood on pancreatic secretion and duodenal migrating myoelectric complex (MMC)
      was studied in four calves. Simultaneous MMC recordings and collections of
      pancreatic juice were performed on valves that had been fasted overnight.
      Intraduodenal (0, 100, and 300 pmol/kg body wt) and intravenous (0, 30, and
      100/pmol kg) infusions of CCK-8 were made for 5 min during the no spiking
      activity (NSA) phase of duodenal MMC associated with a nadir of periodic
      pancreatic secretion. CCK-8 was also administered during continuous atropine
      infusion (5 micrograms/kg/min). Both intraduodenal and intravenous infusions of
      CCK-8 resulted in marked pancreatic responses in juice outflow, bicarbonate
      output, and protein output. Atropine decreased pancreatic response (protein
      output) to intravenous CCK-8 and markedly inhibited the response (juice flow,
      bicarbonate, and protein output) to intraduodenal CCK-8. Infusions of CCK-8 did
      not affect the duration of MMC in the duodenum. Plasma CCK increased
      significantly after intravenous infusion, but remained unchanged after
      intraduodenal infusion. In conclusion, CCK-8 can stimulate pancreatic secretion
      from the duodenal lumen, possibly via a cholinergic mechanism in the calf.

PMID- 7642975
TI  - Prognostic value of histological grading in ductal adenocarcinoma of the
      pancreas. Kloppel vs TNM grading.
AB  - A new histological grading system with prognostic correlation for pancreatic
      cancer was proposed by Kloppel et al. in 1985. Histological sections from 60
      ductal adenocarcinomas operated on between January 1980 and December 1990 were
      retrospectively reviewed in order to compare Kloppel's grading with standard
      TNM's grading and assess their prognostic value. Kloppel grading was determined
      through the following histologic and cytologic factors: number duct-like
      structures, mucus production, neoplastic epithelium, arrangement and pleomorphism
      of nuclei, and mitotic activity. A score from 0 (well differentiated) to 2
      (poorly differentiated) was given to each factor. The mean value obtained
      dividing the sum of the different values by the number of parameters was used to
      construct a malignancy scale and therefore allocate each patient to his Kloppel
      grading. The concordance index K between the two grading systems was relevant (K
      = 0.85 p < 0.001). There was no relation either between gradings (Kloppel or TNM)
      and preoperative duration of symptoms or between gradings and UICC stages. TNM's
      G2 grades of malignancy, N status, and tumor stage were significantly related to
      survival time (p < 0.05). Kloppel's grading does not show any advantage over the
      classical and simpler TNM's grading, even though it can be considered more
      objective and therefore more easily reproducible. This characteristic further
      should be enhanced by the introduction of a malignancy scale such as the "mean
      value."

PMID- 7642976
TI  - Ductal adenocarcinoma of the pancreas associated with intratumoral calcification.
AB  - An invasive ductal carcinoma of the pancreas with intratumoral calcification is
      reported in a 59-yr-old female. The calcification was preoperatively demonstrated
      by ultrasonography and computed tomography. On the cut surface of the resected
      specimen of the pancreas tail, calcification was observed in the central part of
      the ductal adenocarcinoma. Although calcification is not uncommon in chronic
      pancreatitis or serous cystadenoma, mucinous cystadenoma/adenocarcinoma, solid
      and cystic tumor, and islet cell tumor, intratumoral calcification is uncommon in
      an ordinary ductal adenocarcinoma of the pancreas. For differential diagnosis
      from other conditions associated with calcification, careful examinations are
      necessary.

PMID- 7642977
TI  - ECG of the month. A fine thread. Atrial flutter.

PMID- 7642978
TI  - Tumors of the external ear.
AB  - A variety of medical specialists are exposed to patients who seek treatment of
      external ear neoplasms. They are uncommon occurrences, and malignancies of the
      external ear are even rarer. Only 1 patient in 10,000 with an ear complaint will
      have a pathologically proven malignancy of the external ear. Tumors of the
      external ear, both malignant and benign, commonly resemble one another. A timely
      and correct diagnosis is necessary to avoid affecting the external ear's ability
      to collect sound, but also to avoid the more morbid and mortal complications of
      an external ear malignancy. This paper briefly outlines the epidemiology of
      external ear tumors, their etiology, related histopathology, and treatment, which
      encompasses a myriad of modalities and specialties.

PMID- 7642979
TI  - A 72-year-old woman with non-Hodgkin's lymphoma, dyspnea, vomiting, diarrhea, and
      eosinophilia.

PMID- 7642980
TI  - Is it ever permissible for a physician to shorten a human life?
AB  - Medicine makes an important distinction by saying it is sometimes proper to allow
      a patient to die but that one should never actively cause a patient to die. The
      thin, invisible line which separates these views is being tested and will be
      debated intensely in the future.

PMID- 7642981
TI  - Galactosemia: clinical features, diagnosis and management. A case report.
AB  - The case report and discussion presented here were prepared in response to
      legislation in Louisiana which requires that the Dept of Health and Hospitals
      establish a program to inform physicians and hospitals of the current medical
      standards for the diagnosis, clinical management, and recognition of
      galactosemia. Classical galactosemia is an inborn error of galactose metabolism
      caused by a deficiency of galactose-1-phosphate uridryl transferase. It is
      inherited as an autosomal recessive trait and its estimated occurrence is
      1/60,000. The presenting symptoms which include vomiting, diarrhea, jaundice, and
      failure to thrive result from the ingestion of foods containing galactose--breast
      milk and formulas containing cow's milk. Although some states routinely screen
      all newborns for galactosemia, the results of the newborn screening are often not
      available before the infant presents with symptoms. Early recognition and
      immediate withdrawal of galactose from the diet can prevent serious morbidity and
      mortality. There is significant clinical variability and not all infants present
      with typical acute manifestations of the disease.

PMID- 7642982
TI  - Physician assistants and nurse practitioners in Louisiana.
AB  - In recent years there has been tremendous growth in the medically related
      professions of Louisiana. Two such groups are physician assistants and nurse
      practitioners. The following article presents an overview of the development of
      these two fields and their geographic distribution in the state relative to
      Health Professional Shortage Areas.

PMID- 7642983
TI  - Large scrotal epidermal inclusion cyst and hydrocele.

PMID- 7642984
TI  - Crown Prince Frederick of Prussia: Suez and syphilis. Un canard devoile.
AB  - Frederick III (Crown Prince of Prussia, and Emperor of Germany) died of cancer of
      the larynx in 1888. In Drame Imperial (1888) journalist Jean de Bonnefon asserted
      that the disease was not cancer but syphilis which the Crown Prince acquired in
      1869 in Suez. What de Bonnefon wrote about the prince does not coincide with the
      prince's itinerary published in the London Times. This discrepancy is examined
      and the reason for de Bonefon's claim is considered. The report that Crown Prince
      Frederick of Prussia caught syphilis in Suez is a canard.

PMID- 7642985
TI  - The laryngectomee and swimming.
AB  - Following laryngectomy patients are usually advised that swimming is no longer
      possible. Under supervised conditions and using a swimming aid, such as
      described, a laryngectomee may return to an activity previously considered
      unavailable, rehabilitation thus being more complete. However, for a
      laryngectomee to proceed a safe supervised environment is required, and the path
      to this goal is often long and arduous, but with persistent dedication the
      Laryngectomy Swimming Club may become a reality bringing rich reward.

PMID- 7642986
TI  - Valve section of the eustachian tube.
AB  - Research on the eustachian tube (ET) and related paratubal structures was carried
      out by serial section of the temporal bone-ET specimens. In the cadaveric
      studies, the mid-cartilaginous section of the ET presented a curved slit-like
      lumen. It is believed that this section functions principally as a valve
      mechanism and acts like an active sphincter of the ET. This report illustrates
      the dynamic movement of the valve section in a living ET which can be observed by
      using a superfine fibreoptic videomicroendoscope. Disorders of the open-close
      mechanism of the valve section in a diseased ET due to different aetiologies are
      also discussed. This study indicated that transtympanic ET microendoscopy had
      considerable potential for exploring fascinating new aspects of the physiology,
      pathophysiology and anatomy dynamics of the ET.

PMID- 7642987
TI  - Tympanic membrane atelectasis in childhood otitis media with effusion.
AB  - A prospective study on the dynamics of tympanic membrane atelectasis during the
      treatment for glue ear was performed in a sample of 115 ears of 83 children aged
      between one and 11 years. The progression in the degree of pars tensa atelectasis
      was analysed in relation to six potentially relevant factors. Multivariate
      analysis showed that the factor with the most predictive value on the progression
      of the pars tensa retraction was the grade of atelectasis at initial detection (p
      < 0.0001). The use of grommets did not have any significant influence on the
      outcome grade of atelectasis. There was an association between previous grommet
      insertion and localized retractions in the inferior segment of the pars tensa (p
      < 0.0001). However, localized retractions in the postero-superior quadrant were
      not associated with previous grommet insertion (p < 0.02). Although the hearing
      thresholds of atelectatic ears were significantly worse than normal ears
      especially at 4 kHz (p < 0.006), the difference was less than 5 dB.

PMID- 7642988
TI  - Anticipation in Meniere's disease.
AB  - The aetiology of Meniere's disease (MD) remains obscure, but is likely to be
      multifactorial, one of the factors being a genetic predisposition. Forty-one
      families with more than one living member with MD were ascertained and affected
      and normal relations examined. Blood was collected and DNA extracted and stored.
      In these families the mode of inheritance is autosomal dominant, the penetrance
      of the mutation being about 60 per cent. Some of the family members exhibit a
      partial syndrome, vestibular symptoms predominating. Sporadic and familial cases
      exhibit the same clinical features. The striking finding is the phenomenon of
      anticipation, whereby with successive generations there is an earlier age of
      onset and a tendency to more severe manifestation. The inference, considering
      that the cells which regulate endolymph are of neuroectodermal origin, is that,
      like other neurodegenerative disorders which show anticipation, MD manifestation
      is likely to be related to trinucloetide expansion within a gene.

PMID- 7642989
TI  - Monitoring fluctuations in nasal patency in children: acoustic rhinometry versus
      rhinohygrometry.
AB  - Simple rhinohygrometry and passive rhinomanometry studies have suggested that the
      'nasal cycle' in children is often different in pattern of that of adults and
      experimental animals. We aimed to establish whether this assertion was correct,
      using a reliable and sensitive method, acoustic rhinometry (AR), and to compare
      results with those of simple rhinohygrometry (RH). Healthy children with no
      evidence of nasal disease were examined (n = 15; age range three to 10 years;
      mean age six years). Simultaneous recordings using AR and RH were made on each
      child every 10-15 minutes over two to four hour periods. Six children underwent
      nine additional AR studies on separate occasions. 'Classical' reciprocal
      alternating patterns were evident in 80 per cent (12/15) AR and 53 per cent
      (8/15) RH studies, 'in concert' patterns in seven per cent (1/15) AR and 20 per
      cent (3/15) RH studies and 'irregular' patterns in 13 per cent (2/15) AR and 27
      per cent (4/15) RH studies. The agreement between the two methods was 47 per
      cent, with a kappa (kappa) value of -0.17 (poor agreement compared to chance).
      Agreements between the acoustic rhinometry parameters were 'fair' for all data
      (kappa = 0.34) and excellent (kappa = 1.0) if irregular patterns were ignored.
      Repeated studies showed that the pattern of fluctuation varies within any
      particular individual. The nasal cycle is similar in pattern in children and
      adults, and acoustic rhinometry is currently the method of choice to further
      investigate and clarify this phenomenon.

PMID- 7642990
TI  - Scanning electron microscopy findings of human respiratory cilia in chronic
      sinusitis and in recurrent respiratory infections.
AB  - Acute and chronic infections cause morphological changes in the respiratory
      mucosa. The ultrastructure of human respiratory mucosa was studied by scanning
      electron microscopy from the maxillary sinuses of 28 patients, with chronic
      sinusitis, from middle turbinates of 60 patients, with recurrent respiratory
      infections, and from healthy sphenoidal sinuses of 31 patients. A loss of
      ciliated cells and an increasing number of nonciliated columnar cells with
      microvilli were seen in 62 per cent of the maxillary sinus mucosa. Ciliary
      disorientation was seen in 81 per cent of the chronically infected sinus mucosa
      and eight per cent in the healthy sphenoidal sinuses. Also metaplasia and
      extrusion of epithelial cells were prominent in chronic infections. Compound
      cilia were seen in 52 per cent of the samples from patients with chronic
      sinusitis and in 31 per cent of the healthy sphenoidal sinuses. Short cilia were
      often seen in infected mucosa indicating ciliogenesis.

PMID- 7642991
TI  - KTP-532 laser tonsillectomy--a potential day-case procedure?
AB  - We report the results of a prospective pilot study of 54 adult patients
      undergoing tonsillectomy using the KTP-532 laser, designed to assess whether the
      technique would facilitate day-case adult tonsillectomy. Subjective and objective
      assessment at six hours post-operatively showed that only 43 per cent could, in
      our judgement, have been discharged at this interval. Furthermore, the overall
      complication rate was 31 per cent with a secondary haemorrhage rate of 19 per
      cent. We conclude that KTP-532 laser tonsillectomy as performed in this pilot
      study compares unfavourably with dissection tonsillectomy and we discuss possible
      reasons for this.

PMID- 7642992
TI  - Lingual thyroid: tongue-splitting incision for transoral excision.
AB  - Two patients presenting to the Central Military Hospital of Beirut with
      symptomatic lingual thyroid are reported. I131 thyroid scanning revealed the
      lingual thyroid to be the only functional thyroid tissue present in each patient.
      Subsequent CT scanning demonstrated the large size of these ectopic thyroids
      causing significant mechanical obstruction. These were excised transorally using
      a posterior midline tongue-splitting incision and reimplanted in the rectus
      abdominis muscles. Details of this modified tongue-splitting surgical approach
      are described. A brief review of the literature concerning lingual thyroid and
      its surgical treatment is also presented as well as three patients operated on
      for lingual thyroid at the American University of Beirut Medical Centre between
      1975 and 1994 using an external neck incision.

PMID- 7642993
TI  - Non-tuberculous mycobacterial infections presenting as salivary gland masses in
      children: investigation and conservative management.
AB  - Non-tuberculous mycobacterial (NTM) infections in children commonly present as
      cervicofacial masses. The importance of early diagnosis is in the exclusion of
      infection requiring treatment, particularly tuberculosis and the rare case of
      malignancy. Five children with NTM presenting with salivary gland masses
      illustrate the value of skin testing with new tuberculins and the place of fine
      needle aspiration cytology in the investigation of these infections. Four
      children who were skin tested reacted specifically to one of the new tuberculins,
      two indicating infection with Mycobacterium malmoense, confirmed by culture, the
      others responding to tuberculins from M. scrofulaceum and M. avium
      intracellulare, neither having a positive culture. The one case not skin tested
      produced M. avium-intracellulare on culture. All five patients were managed
      conservatively. The place for conservative management when the facial nerve is at
      risk and extensive skin excision is indicated are discussed.

PMID- 7642994
TI  - Audit of the treatment of tonsillar and peritonsillar sepsis in an ear, nose and
      throat unit.
AB  - We became aware that a range of antibiotics were being used in our unit to treat
      patients suffering from tonsillitis or peritonsillar abscess (quinsy). There
      appeared to be no rationale to determine which antibiotics were used, and we felt
      that we were possibly using expensive antibiotics when cheaper equally effective
      ones were available. An audit project was therefore devised to establish the
      current practice in the ENT Unit at the City Hospital at Edinburgh. Following a
      six-month prospective pilot study, a protocol for the treatment of tonsillar and
      peritonsillar sepsis was drawn up and subsequent practice and outcome was then
      audited, thus completing the audit cycle. As a result substantial savings in the
      cost of prescribed antibiotics have been made without compromising patient care.

PMID- 7642995
TI  - Nasendoscopy guided removal of fish bones from the base of tongue and the
      vallecula.
AB  - Impaction of a fish bone at the base of tongue or the vallecula is a very common
      problem. Removal of the bone from these sites without a general anaesthesia can
      be challenging to surgeons and patients alike. Various manoeuvres to facilitate
      this procedure have been described, some are very successful but may require
      specialized instruments, while others may cause excessive discomfort to the
      patients and even inadvertent dislodgement of the bone. We describe a method
      using a flexible fibreoptic nasendoscope to provide a visual guide in order to
      facilitate peroral removal of the bone with a pair of forceps. This method is
      well tolerated by patients and avoids the need for a general anaesthesia in many
      cases.

PMID- 7642996
TI  - Improving the reproducibility of acoustic rhinometry: a customized stand giving
      control of height and angle.
AB  - Control and recording of the position of the acoustic rhinometer in relation to
      the nostrils is important for serial measurements. Several technical factors must
      be controlled, including the angle of the incident acoustic wave. We describe a
      simple, newly-designed, rhinometer stand which allows control of height and
      angle, and hence improves the reliability of serial measurements in clinical and
      physiological work.

PMID- 7642997
TI  - Giant cell tumour of the temporal bone presenting as vertigo.
AB  - We report a case of giant cell tumour of the temporal bone arising in a 31-year
      old man. The presenting symptoms were unusual, being rotational vertigo,
      unilateral tinnitus, and hearing loss. A computed tomography (CT) scan showed a
      large mass within the right temporal bone and the infratemporal fossa. The
      radiological appearance was suggestive of an aggressive primary neoplasm arising
      within bone. Biopsy and subsequent resection showed a giant cell tumour of bone.
      The tumour was histological grade 1. At two-year follow-up, there was no evidence
      of tumour recurrence or metastasis.

PMID- 7642998
TI  - An unusual cause of cochlear implant failure.
AB  - We present a cochlear implant failure previously unidentified and unreported.
      Following successful implantation and activation of a Cochlear Mini 22 system, a
      distressing barrage of crackling noises was heard by the patient despite repeated
      programming with threshold and comfort level adjustment. The implant soon became
      nonfunctional and integrity testing showed deficient electrical responses and
      abnormal surface measured wave forms. Investigation of the explant, following
      reimplantation with an identical system, showed a defective trim capacitor, an
      electric component of the internal circuit in the stimulator. Paired Student's t
      test showed a marginally significant increase (p = 0.047) in effective threshold
      level and a highly significant decrease (p = 0.0002) in maximum comfort level for
      the second implant compared to the first implant.

PMID- 7642999
TI  - A case with symptoms of vestibular neuronitis caused by an intramedullary lesion.
AB  - We report on a patient with an intramedullary lesion who showed only symptoms of
      so-called vestibular neuronitis. From the neurological aspects and MRI findings,
      the lesion was thought to be localized to the vestibular nerve in the pons.
      Cerebrospinal fluid testing and MRI findings suggested a diagnosis of multiple
      sclerosis (MS), although the clinical features were not compatible with MS. This
      case may shed some light on the aetiology of vestibular neuronitis.

PMID- 7643000
TI  - Superficial siderosis of the central nervous system: a case with an unruptured
      intracranial aneurysm.
AB  - We present a case of superficial siderosis (SS) of the central nervous system
      (CNS) with an unruptured intracranial aneurysm to illustrate that the commonly
      encountered unexplainable progressive sensorineural hearing loss (SNHL) can be an
      important sign for the early awareness of this rare disorder. The literature on
      SS is reviewed and the pathogenesis of SS is discussed.

PMID- 7643001
TI  - Antrochonal polyp: a case report of treatment with intranasal steroids.
AB  - The aetiology of antrochonal polyps is unknown. We report one case where
      treatment with topical intranasal cortico-steroids was successful. We are not
      aware of any previous reports of medical treatment.

PMID- 7643002
TI  - Giant cell reparative granuloma of the concha bullosa.
AB  - Giant cell reparative granuloma is a benign lesion occurring most commonly in the
      bones of the jaw and rarely in the paranasal sinuses. We present an unusual case
      of giant cell reparative granuloma arising within a concha bullosa. Complete
      excision was achieved using an endoscopic transnasal approach.

PMID- 7643003
TI  - An unusual complication following inferior turbinectomy.
AB  - Neurological complications following turbinate surgery are relatively rare. We
      present here an unusual complication of unilateral partial oculomotor and
      trigeminal nerve palsy after bilateral inferior turbinectomies. The probable
      aetiological mechanism is discussed.

PMID- 7643004
TI  - Acute airway obstruction due to ruptured aneurysmal arterio-venous fistula:
      common carotid artery to internal jugular vein.
AB  - Fistulae between major vessels in the head and neck are uncommon. In both
      civilian and wartime reports, the total number of traumatic arterio-venous
      fistulae in head and neck region account for less than four per cent of all
      arterial injuries. Fourteen cases of congenital communication between the
      external carotid artery and external or internal jugular vein have been reported.
      We report and discuss the management of a case of ruptured carotico-jugular
      fistula secondary to infection which presented as acute upper airway obstruction.
      This appears to be the first description of such a case in the literature.

PMID- 7643006
TI  - Oncocytic differentiation in salivary gland tumours.
AB  - An oncocytic mucoepidermoid carcinoma and an oncocytic pleomorphic adenoma
      occurred in a 47-year-old male and a 75-year-old female, respectively. Both
      presented as asymptomatic parotid gland masses without evidence of facial nerve
      paralysis and were treated by superficial parotidectomy. There has been no
      evidence of recurrence or metastasis. Oncocytic change is rare in major salivary
      gland mucoepidermoid carcinoma with only two previously reported cases. Marked
      oncocytic transformation of pleomorphic adenomas can cause their confusion with
      oncocytomas. Recognition of oncocytic differentiation in various salivary gland
      tumours is important to avoid misclassification of these lesions.

PMID- 7643005
TI  - Benign osteoblastoma of the mastoid part of the temporal bone: case report.
AB  - Osteoblastoma is a benign bone lesion that mainly affects the long bones and
      rarely the temporal bones. Very few cases have been reported in the literature.
      This paper reviews the literature, discusses the differential diagnosis, clinical
      presentation, and CT scan findings of such a condition and details our experience
      with a young patient who had a temporal bone (mastoid process) osteoblastoma.

PMID- 7643008
TI  - Defensins and other endogenous peptide antibiotics of vertebrates.
AB  - Gene-encoded peptide antibiotics are ubiquitous components of host defenses in
      mammals, birds, amphibia, insects, and plants. Their de novo synthesis or release
      from storage sites can be induced rapidly, which makes them particularly
      important in the initial phases of resistance to microbial invasion. The
      endogenous antimicrobial peptides of animals are products of single genes and are
      synthesized as preproproteins. Multistep processing yields the mature peptide,
      which generally acts by inducing microbial membrane permeabilization. Several
      families of antimicrobial peptides have been identified that differ with respect
      to the presence of disulfide linkages, amino acid composition, structural
      conformation, and spectrum of activity. The arginine-rich three disulfide
      containing beta-sheet defensins are remarkably abundant and widely distributed in
      animals and plants. The antibiotic peptides of higher eukaryotes merit further
      study for their role in natural immunity and their potential as novel therapeutic
      compounds.

PMID- 7643007
TI  - Proteases and protease receptors in modulation of leukocyte effector functions.
AB  - Cellular immune responses depend on regulated pathways of intracellular signal
      transduction and leukocyte activation. Although these mechanisms are coordinated
      by a variety of leukocyte-restricted effector molecules, recent observations have
      uncovered a novel role of proteases in transducing outside-in signals of
      leukocyte activation. Through regulated, receptor-mediated recognitions,
      coagulation and fibrinolytic enzymes or effector cell granular proteases
      influence monocyte motility and chemotaxis, modulate pleiotropic cytokine
      responses, contribute to mononuclear cell proliferation, or induce target cell
      apoptosis. Overall, these mechanisms define a novel interface between general
      inflammatory reactions, invariably characterized by activation of blood protease
      cascades, and specialized aspects of cellular immune functions.

PMID- 7643009
TI  - Associations between the neuroendocrine and immune systems.
AB  - Organisms respond to infection with complex adaptations involving bidirectional
      communication between the immune and neuroendocrine systems. The idea of
      intercellular communication between the neuroendocrine and immune systems via
      common signal molecules has provided a conceptual framework for such crosstalk.
      The studies to date show that cells of the immune system contain receptors for
      neuroendocrine hormones and can also be considered a source of pituitary and
      hypothalamic peptides. The structure and pattern of synthesis of these peptides
      by leukocytes appear similar to neuroendocrine hormones, although some
      differences exist. Once secreted, these peptide hormones may function as
      endogenous regulators of the immune system as well as conveyors of information
      from the immune to the neuroendocrine system. The plasma hormone concentrations
      contributed by lymphocytes usually do not reach the levels required when the
      pituitary gland is the source, but because immune cells are mobile, they have the
      potential to locally deposit the hormone at the target site. Likewise, other
      studies show that cells of the neuroendocrine system contain receptors for
      cytokines and can also be considered a source of cytokines, particularly
      interleukin-1 (IL-1) and IL-6. In the pituitary IL-1 beta coexists with thyroid
      stimulating hormone in a subpopulation of thyrotropes, suggesting it may have a
      role as a pituitary paracrine factor. The cytokines, including IL-1, IL-2, IL-6,
      interferon-gamma, and tumor necrosis factor, exert profound effects on
      hypothalamic pituitary axes. It is our hypothesis that the relay of information
      to the neuroendocrine system represents a sensory function for the immune system
      wherein leukocytes recognize stimuli that are not recognizable by the central and
      peripheral nervous systems (i.e., bacteria, tumors, viruses, and antigens). The
      recognition of such noncognitive stimuli by immunocytes is then converted into
      information and a physiological change occurs. Future studies into the
      physiological role that cytokines and neuroendocrine hormones have in these
      systems will be of considerable interest for both immunologists and
      endocrinologists.

PMID- 7643010
TI  - Recombinant human IL-7 administration in mice affects colony-forming units-spleen
      and lymphoid precursor cell localization and accelerates engraftment of bone
      marrow transplants.
AB  - Murine reconstitution assays were used to investigate the effects of recombinant
      human interleukin-7 (rhIL-7) on myeloid and lymphoid precursors and on bone
      marrow engraftment. Reconstitution with bone marrow from rhIL-7-treated mice
      results in a 3.4-fold decrease in total colony-forming unit-spleen (CFU-S)
      activity (day 9) and an 18.1- and 11.9-fold decrease in its ability to generate
      thymocytes and splenic B lineage cells, respectively. In contrast, after
      reconstitution with splenocytes from rhIL-7-treated mice, CFU-S activity
      increased 23.6-fold (day 9) and the thymocyte and splenic B lineage cell
      regenerative capacity increased by 4.0- and 3.2-fold, respectively. In addition,
      CD43low+, B220low+ cells that contain pre-pro-B cells and pro-B cells were
      expanded two- to threefold and Ig mu-, B220+, CD2- and Ig mu-, B220+, CD2+ B
      lineage cells were expanded approximately 10-fold and 10- to 45-fold (depending
      on the tissue examined), respectively, after rhIL-7 treatment. Administration of
      rhIL-7 to irradiated mice transplanted with bone marrow resulted in accelerated T
      cell and B cell reconstitution by up to 2-4 weeks. Thus, rhIL-7 administration
      affects the distribution of myeloid and lymphoid precursors. Moreover, rhIL-7
      administration accelerates murine bone marrow cell engraftment and therefore may
      be useful in reducing the engraftment time in bone marrow transplant patients.

PMID- 7643011
TI  - CD4+ contrasuppressor T cells improve the resistance of thermally injured mice
      infected with HSV.
AB  - Modulation of burn-associated CD8+ CD11b+ T cell receptor gamma/delta+ suppressor
      T cells (BA2T cells) and improved resistance to herpesvirus infections was
      studied in thermally injured mice. The susceptibility of thermally injured mice
      to infection by herpes simplex virus (HSV) was approximately 100 times greater
      than it was in normal mice. The increased susceptibility of thermally injured
      mice to HSV infection was transferred to normal mice by BA2T cells, which
      appeared in spleens of mice 2-9 days after thermal injury. The suppressor cell
      activity of BA2T cells was effectively counteracted by CD4+ CD28+ T cell receptor
      alpha/beta+ Vicia villosa lectin adherent antisuppressor cells (designated as
      burn-induced contrasuppressor T cells; BCS cells), which were generated naturally
      in spleens of mice after the appearance of BA2T cells. The adoptive transfer of
      BCS cells to mice just after the injury improved the resistance of thermally
      injured mice to HSV infection to levels observed in normal mice. These results
      suggest that the increased susceptibility of thermally injured mice to HSV
      infection may be affected by BA2T suppressor cells and BCS cells may improve the
      resistance of thermally injured mice to HSV infection through the inhibition of
      BA2T suppressor cell activities.

PMID- 7643012
TI  - C1q triggers neutrophil superoxide production by a unique CD18-dependent
      mechanism.
AB  - Complement protein C1q induces the production of superoxide (O2-) by neutrophils
      via an as yet unidentified receptor or receptor complex. Several strategies were
      therefore used to identify cell surface molecules involved in the response of
      neutrophils to C1q and its collagen-like domain (C1q-CLR). Treatment of
      neutrophils with phosphatidylinositol-specific phospholipase C effectively
      removed the phosphatidylinositol-linked surface molecules CD14 and CD16, yet did
      not reduce O2- production in response to C1q. Next, 17 monoclonal antibodies
      (mAbs) recognizing various neutrophil surface antigens were tested for their
      ability to inhibit C1q-CLR-mediated O2- production. Only two of the mAbs, 44a and
      IB4, which recognize CD11b/CD18 (complement receptor 3 or Mac-1), were
      inhibitory. In addition, neutrophils from a patient with leukocyte adhesion
      deficiency, which are CD18 deficient, did not produce O2- in response to C1q or
      C1q-CLR. Because CD11b/CD18 is recognized to play a role in cell adhesion, the
      role of adherence in C1q-mediated O2- production was explored. Adherence of
      neutrophils to C1q-CLR-coated surfaces occurred with kinetics, which usually
      paralleled those of O2- production, and was invariably abolished by the anti
      CD11b mAb 44a. However, this mAb often only partially inhibited O2- production,
      indicating that an avid attachment of neutrophils to the C1q-CLR-coated surface
      is not required for O2- production.

PMID- 7643014
TI  - Nitric oxide stimulates ADP ribosylation of actin in association with the
      inhibition of actin polymerization in human neutrophils.
AB  - In these studies we provide conclusive evidence that (beta/gamma) actin present
      in human neutrophils is a substrate for nitric oxide (NO)-dependent ADP
      ribosylation and that this modification is associated with the inhibition of
      actin polymerization. A 43-kDa substrate for NO-dependent ADP ribosylation was
      identified as actin by four methods: (1) comigration with the botulinum C2 toxin
      substrate by two-dimensional gel electrophoresis (pI 5.2), (2) identity between
      the peptide map generated by V8 protease digestion of the NO and botulinum C2
      substrates, (3) immunoprecipitation with antiactin antibodies, and (4) the
      ability of NO to ADP ribosylate purified neutrophil G-actin in the presence of
      plasma membrane cofactors. Because the ADP ribosylation of actin by the botulinum
      C2 toxin is known to inhibit F-actin polymerization, we examined the effect of NO
      on actin assembly. Flow cytometry revealed that NO inhibited formyl-methionine
      leucine-phenylalanine (fMLP)-dependent (30 s at 37 degrees C) F-actin formation
      (108 +/- 8 vs. 89 +/- 6 relative fluorescence units, P < .02). These results were
      confirmed by quantification of F-actin formation by gel scanning (10% sodium
      dodecyl sulfate gel, Coomassie, and densitometry): pretreatment of
      polymorphonuclear leukocytes with NO resulted in a reduction of fMLP-induced,
      cytoskeletal-associated F-actin, which was accompanied by an increase of Triton
      soluble G-actin. NO also inhibited F-actin formation, as observed by means of
      rhodamine phalloidin staining of neutrophils adherent to a fibronectin-coated
      surface. This effect was accompanied by a dose-dependent inhibition of neutrophil
      adherence in NO-treated cells. The data indicate that NO inhibits cytoskeletal
      assembly and adherence in human neutrophils in association with the ADP
      ribosylation of actin.

PMID- 7643013
TI  - Phorbol ester-induced priming of superoxide generation by phosphatidic acid
      stimulated neutrophils and granule-free neutrophil cytoplasts.
AB  - This study was undertaken to examine the mechanisms involved in polymorphonuclear
      leukocyte superoxide release stimulated by exogenous phosphatidic acid (PA).
      Unlike the immediate burst of superoxide release affected by membrane-permeable
      dioctanoylglycerol (DiC8-DAG), dioctanoyl phosphatidic acid (DiC8-PA) induced
      superoxide release after a lag period of 5-20 min. This period was considerably
      reduced or eliminated when cells were primed by substimulatory levels of phorbol
      myristate acetate (PMA). Granule-depleted neutrophil cytoplasts also responded to
      DiC8-PA with a burst of superoxide generation. Activation of the cytoplast
      superoxide generating system in response to DiC8-PA was also significantly faster
      after cells had been preexposed to substimulatory levels of PMA, indicating that
      at least a portion of the priming mechanism was independent of PMA-induced
      degranulation. To further examine the potential mechanism of PMA priming of
      responses to PA, we evaluated the activity of neutrophil ecto-phosphatidic acid
      phosphohydrolase (ecto-PA phosphohydrolase), which generates diacylglycerol from
      exogenous PA. PMA priming had no discernable effect on the activity of this
      enzyme. In addition, propranolol, an inhibitor of PA phosphohydrolase, did not
      selectively inhibit PMA priming of neutrophil responses to DiC8-PA, indicating
      that priming did not result from acceleration of DiC8-PA hydrolysis. We therefore
      investigated the possibility that activation of protein kinase C was the basis of
      the primed response. Several semiselective protein kinase C inhibitors
      (calphostin C, H-7, and acylmethylglycerol) inhibited DiC8-DAG- and DiC8-PA
      induced superoxide release as well as PMA-primed responses to approximately the
      same extent. These results are consistent with the hypothesis that neutrophil
      responses to phosphatidate are mediated by diglyceride generated by the action of
      ecto-PA phosphohydrolase. PMA priming does not result from increased catalytic
      activity of ecto-PA phosphohydrolase but rather seems to result from potentiation
      of an intermediate involved in the cells' response to multiple stimuli.

PMID- 7643015
TI  - Cellular and molecular mechanisms of IFN-gamma production induced by IL-2 and IL
      12 in a human NK cell line.
AB  - Interferon-gamma (IFN-gamma) is an important immunoregulatory protein produced
      predominantly by T cells and large granular lymphocytes (LGL) in response to
      different extracellular signals. In particular, two interleukins (ILs), IL-2 and
      IL-12, have been shown to be potent inducers of IFN-gamma gene expression in both
      T cells and LGL. Although it has been reported that there are some T cell lines
      that produce IFN-gamma in response to IL-2 and IL-12 stimulation, there has as
      yet been no report of a natural killer (NK) cell line that responds in a similar
      manner. In this report we present evidence that the cell line NK3.3 derived from
      human NK cells, responds to both IL-2 and IL-12, as measured by increases in IFN
      gamma and granulocyte-macrophage colony-stimulating factor (GM-CSF) cytoplasmic
      mRNA and protein expression. In addition, when used together IL-2 and IL-12
      synergized in the induction of IFN-gamma and GM-CSF and this synergy was
      attributed to an increased accumulation and stability of the IFN-gamma and GM-CSF
      mRNAs. To investigate the signaling pathways involved in the gene induction, five
      inhibitors, cyclosporin A (CsA), transforming growth factor-beta, cycloheximide,
      genistein, and staurosporine A, were used in analyzing the effects of IL-2 and IL
      12 on NK3.3 cells. The results suggest that activation of protein kinase C, but
      not new protein synthesis, is required for IL-2 induction of IFN-gamma and GM-CSF
      cytoplasmic mRNA. In contrast, IL-12 induction of IFN-gamma cytoplasmic mRNA
      appears to only partially depend on activation of protein kinase C. Furthermore,
      both transforming growth factor-beta and genistein, a tyrosine kinase inhibitor,
      could suppress IL-2 and IL-12 signaling but CsA was generally inactive. It also
      was observed that suppression of cytokine gene expression by these agents was
      independent of the inhibition of proliferation. In addition, IL-2 but not IL-12
      induced nuclear factors NF-kappa B and AP1, and regulation of the nuclear levels
      of these two DNA binding protein complexes is correlated with IFN-gamma and GM
      CSF gene expression. These data indicate that IL-2 and IL-12 may have distinct
      signaling pathways leading to the induction of IFN-gamma and GM-CSF gene
      expression, and that the NK3.3 cell line may serve as a novel model for
      dissecting the biochemical and molecular events involved in these pathways.

PMID- 7643016
TI  - Supernatants from UVB radiation-exposed keratinocytes inhibit Langerhans cell
      presentation of tumor-associated antigens via IL-10 content.
AB  - Exposure of mice to midrange UV radiation (UVB) (280-320 mm) in vivo leads to
      suppression of the ability to induce delayed-type hypersensitivity (DTH).
      Systemic administration of supernatants from UVB-exposed keratinocytes (KC)
      similarly inhibits the ability to induce DTH and the presence of interleukin-10
      (IL-10) in the supernatants has been shown to be responsible for this effect. It
      has been hypothesized that release of IL-10 by KC after exposure to UVB radiation
      in vivo may be responsible for UVB-induced inhibition of DTH and also for the
      inability of chronically UVB-irradiated mice to immunologically reject
      immunogenic UVB-induced skin tumors. To test directly whether supernatants from
      UVB-irradiated KC can inhibit presentation of tumor-associated antigens (TAA) by
      epidermal Langerhans cells (LC), cultures of the transformed murine KC line PAM
      212 were exposed to 200 J/m2 of UVB radiation and 24 h supernatants obtained.
      CAF1 (H-2a/d) epidermal cells (EC) enriched for LC content were exposed to
      supernatants from irradiated (UV-SN) or mock-irradiated (MI-SN) PAM 212 cells for
      3 h followed by culture for 16 h in granulocyte-macrophage colony-stimulating
      factor and then were pulsed with soluble TAA derived from the murine spindle cell
      tumor S1509a (H-2a). ECs were then washed and injected subcutaneously into naive
      CAF1 mice three times at weekly intervals for priming. One week after the final
      immunization these mice were challenged subcutaneously with live S1509a cells and
      tumor growth scored over time. Pretreatment of EC with UV-SN but not MI-SN
      inhibited the induction of effective immunity by this immunization scheme. ECs
      were also treated with UV-SN or MI-SN for 3 h then pulsed with TAA and injected
      into a hind footpad of previously immunized mice for elicitation of a DTH
      response. Pretreatment of EC with UV-SN but not MI-SN inhibited the ability of EC
      to elicit DTH. Neutralization studies with specific neutralizing antibodies to IL
      10 demonstrated that the presence of IL-10 in UV-SN was responsible for the
      inhibition of antigen presentation both for induction and elicitation of
      immunity. UV-SN inhibits tumor antigen presentation by epidermal LC through the
      action of IL-10.

PMID- 7643017
TI  - Discrete pathways for arachidonic acid release from tannin versus beta-glucan
      stimulated rabbit alveolar macrophages.
AB  - Previously, we observed both tannin and beta-glucan to be agonists for
      arachidonic acid (AA) release from rabbit alveolar macrophages. Although tannin
      inhibited reincorporation of exogenous AA, beta-glucan had no apparent effect,
      suggesting separate signal transduction pathways leading to elevated AA levels.
      In this study alveolar macrophages were pretreated with the tyrosine phosphatase
      inhibitor sodium orthovanadate then stimulated with either condensed tannin or
      beta-glucan. Vanadate exerted opposing effects on AA release. Furthermore,
      vanadate reversed the ability of tannin to inhibit reacylation. Additional
      studies using the phospholipase A probe bis-BODIPY-C11-PC indicated that although
      the known phospholipase A2 activators, calcium ionophore A23187, insoluble immune
      complexes, and beta-glucan, generated an increase in fluorescence consistent with
      phospholipase A activation, tannin had no effect. These findings suggest the
      increase in free AA resulting from stimulation of macrophages by either tannin or
      beta-glucan is produced via two different mechanisms.

PMID- 7643019
TI  - Synchronous and asynchronous telemedicine.
AB  - This paper outlines the differences between telemedicine applications in terms of
      their synchronous or asynchronous nature. The differences in the demands of these
      two forms of telemedicine are significant and should be considered in the
      development of any telemedicine system. It is the asynchronous applications that
      are most likely to provide real change in the practice of medicine.

PMID- 7643018
TI  - Modulation of IgA, IgE, and IgG Fc receptor expression on human mononuclear
      phagocytes by 1 alpha,25-dihydroxyvitamin D3 and cytokines.
AB  - The effects of 1 alpha,25-dihydroxyvitamin D3/calcitriol on the expression of Fc
      receptors (FcR) for IgA (Fc alpha R), IgE (Fc epsilon RII), and IgG (Fc gamma R)
      on human peripheral blood monocytes and the cell lines U937, THP-1, and Mono Mac
      6, in combination with various cytokines, was examined by flow cytometry. On both
      monocyte-derived macrophages and the myelomonocytic cell lines, Fc alpha R/CD89
      expression was induced by calcitriol alone and additively in combination with
      tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), and
      granulocyte-macrophage colony-stimulating factor. Constitutive and interleukin-4
      (IL-4)-driven Fc epsilon RII/CD23 expression was markedly diminished on
      calcitriol-treated U937 cells and monocytes. Fc epsilon RII was also triggered by
      IFN-gamma, TNF-alpha, and IL-6 on all the cell lines, an effect blocked by
      calcitriol. On monocytes, the basal level and IFN-gamma-induced Fc gamma RI/CD64
      expression was down-regulated by calcitriol and IL-4. The expression of Fc gamma
      RII/CD32 on monocytes was strongly suppressed by calcitriol. Transforming growth
      factor-beta induced Fc gamma RIII/CD16 on monocytes, an effect opposed by
      calcitriol. The ability of calcitriol-treated monocytes to phagocytose IgG
      sensitized ox erythrocytes was diminished. Our results demonstrate that
      calcitriol, alone or in combination with cytokines, modulates Fc alpha R, Fc
      epsilon RII, Fc gamma RI, and Fc gamma RII expression on human mononuclear
      phagocytes, as well as Fc gamma R-mediated phagocytosis.

PMID- 7643020
TI  - Defense Simulation Internet: next generation information highway.
AB  - The Department of Defense has been engaged in the Defense Modeling and Simulation
      Initiative (DMSI) to provide advanced distributed simulation warfighters in
      geographically distributed localities. Lessons learned from the Defense
      Simulation Internet (DSI) concerning architecture, standards, protocols,
      interoperability, information sharing, and distributed data bases are equally
      applicable to telemedicine. Much of the vision and objectives of the DMSI are
      easily translated into the vision for world wide telemedicine.

PMID- 7643022
TI  - NASA high performance computing, communications, image processing, and data
      visualization-potential applications to medicine.
AB  - High-speed information processing technologies being developed and applied by the
      Jet Propulsion Laboratory for NASA and Department of Defense mission needs have
      potential dual-uses in telemedicine and other medical applications. Fiber optic
      ground networks connected with microwave satellite links allow NASA to
      communicate with its astronauts in Earth orbit or on the moon, and with its deep
      space probes billions of miles away. These networks monitor the health of
      astronauts and or robotic spacecraft. Similar communications technology will also
      allow patients to communicate with doctors anywhere on Earth. NASA space missions
      have science as a major objective. Science sensors have become so sophisticated
      that they can take more data than our scientists can analyze by hand. High
      performance computers--workstations, supercomputer and massively parallel
      computers are being used to transform this data into knowledge. This is done
      using image processing, data visualization and other techniques to present the
      data--one's and zero's in forms that a human analyst can readily relate to and
      understand. Medical sensors have also explored in the in data output--witness CT
      scans, MRI, and ultrasound. This data must be presented in visual form and
      computers will allow routine combination of many two dimensional MRI images into
      three dimensional reconstructions of organs that then can be fully examined by
      physicians. Emerging technologies such as neural networks that are being
      "trained" to detect craters on planets or incoming missiles amongst decoys can be
      used to identify microcalcification in mammograms.

PMID- 7643021
TI  - Interventional telemedicine for noninvasive neuroradiosurgery: remote-site high
      performance computing, mathematical optimization, and virtual scenario
      simulation.
AB  - Interventional Telemedicine may have potential utility in providing connectivity
      and access to specialized high performance computing and advanced software
      resources in support of clinical procedures in the field of Minimally-Invasive
      Surgery and Stereotactic Linear Accelerator (LINAC) Radiosurgery. Such
      interventions may benefit from application of nonlinear quadratic inverse
      solution methods designed to provide the capability to reverse optimize a 'best
      case' treatment plan. The formidable decision-making challenges posed by
      increasingly complex optimized data and progressively versatile LINAC delivery
      systems require volume visualization of projected treatment data and imaging
      anatomy via photorealistic rendering and virtual scenario simulation techniques.
      Both these new directions are heavily dependent on access to specialized high
      performance computing platforms solely accessible via broad-bandwidth network
      connectivity. This pilot project presents resimulation of retrospective
      radiosurgical case data using inverse solution optimization models running on
      workstation clusters and then volume rendered and simulated on the Princeton
      Graphics Engine Supercomputer. Evidence for effective utilization of such
      optimization and virtual simulation methods running on remotely accessed, distant
      high performance computing resources is discussed in view of the potential for
      long-term clinical investigation and eventual development of Interventional
      Telemedicine as a clinically practical approach for providing support to remote
      or non-urban radiosurgery centers in the industrialized and developing world.

PMID- 7643023
TI  - Medical applications of virtual reality.
AB  - Medical applications for virtual reality (VR) are just beginning to emerge. These
      include VR surgical simulators, telepresence surgery, complex medical database
      visualization, and rehabilitation. These applications are mediated through the
      computer interface and as such are the embodiment of VR as an integral part of
      the paradigm shift in the field of medicine. The Green Telepresence Surgery
      System consists of two components, the surgical workstation and remote worksite.
      At the remote site there is a 3-D camera system and responsive manipulators with
      sensory input. At the workstation there is a 3-D monitor and dexterous handles
      with force feedback. The VR surgical simulator is a stylized recreation of the
      human abdomen with several essential organs. Using a helmet mounted display and
      DataGlove, a person can learn anatomy from a new perspective by 'flying' inside
      and around the organs, or can practice surgical procedures with a scalpel and
      clamps. Database visualization creates 3-D images of complex medical data for new
      perspectives in analysis. Rehabilitation medicine permits impaired individuals to
      explore worlds not otherwise available to them, allows accurate assessment and
      therapy for their disabilities, and helps architects understand their critical
      needs in public or personal space. And to support these advanced technologies,
      the operating room and hospital of the future will be first designed and tested
      in virtual reality, bringing together the full power of the digital physician.

PMID- 7643024
TI  - Clinical trials to validate telemedicine.

PMID- 7643025
TI  - Telemedicine system evaluation and a collaborative model for multi-centered
      research.
AB  - Evaluating telemedicine systems and services is a complex task. Safety and
      efficacy must be measured in a relatively controlled laboratory environment,
      while measurement of clinical utility and medical effectiveness requires
      extensive field testing. The need for large clinical trials to demonstrate
      utility and effectiveness presents a dilemma. Substantial numbers of cases are
      needed to achieve statistically valid results, yet most telemedicine programs are
      based in rural settings with small patient populations. One potential solution is
      to pool data from multiple programs by using common data collection instruments
      and protocols. A promising model for the performance of multi-centered
      collaborative telemedicine research is described. The Clinical Telemedicine
      Cooperative Group (CTCG) is based on the successful use of collaborative research
      by clinical oncology research groups such as the Southwest Oncology Group (SWOG).

PMID- 7643026
TI  - Keynote address: global connectivity through telemedicine.

PMID- 7643027
TI  - Clinical evaluation of pravastatin in the treatment of type II hyperlipidemia in
      patients with non-insulin-dependent diabetes mellitus.
AB  - The study was conducted on 30 NIDDM patients with type II hyperlipoproteinemia.
      They consisted of 13 males and 17 females with the mean (+/- S.D.) age of 60.6 +/
      7.6 year. They were treated with a daily dose of 10 mg pravastatin given orally
      twice a day for 16 weeks. Their mean (+/- S.D.) serum TC, LDL-C, TG and HDL-C
      levels at week 0 were 259.7 +/- 22.6, 177.4 +/- 20.3, 173.9 +/- 62.3 and 44.0 +/-
      9.9 mg/dl respectively. After receiving pravastatin the maximal reduction of TC,
      LDL-C and TG was 22.9, 31.2 and 17.1 per cent with statistical significant
      difference from the baseline. The maximal increment of HDL-C was 11.9 per cent,
      also showing statistical significant difference from the baseline. Plasma
      glucose, serum fructosamine and glycated hemoglobin were not affected by
      pravastatin. There were no significant changes in the patients' body weight and
      other biochemical parameters except for one case who had transient slight
      increase in transaminase during pravastatin treatment. These results indicate
      that pravastatin is an effective and safe drug in diabetic patients with
      hypercholesterolemia.

PMID- 7643028
TI  - Glomerulonephritis in beta-thalassemia Hb-E disease: clinical manifestations,
      histopathologic studies and outcome.
AB  - We presented 8 patients with beta-thal/Hb E with glomerular diseases. Diverse
      glomerular lesions were seen, but diffuse endocapillary glomerulonephritis was
      the most common. The clinical manifestations of acute glomerulonephritis in beta
      thal/Hb E differed from typical cases in the older age group, female
      preponderance, longer duration of edema, less hypertension, marked proteinuria,
      hypoalbuminemia and hypertriglyceridemia and also a longer period of recovery but
      their outcome was still favorable despite many risk factors of renal injury.
      Renal biopsy was necessary in doubtful cases to detect the correct diagnosis and
      give proper management. The association and mechanism of glomerulonephritis in
      these patients require further prospective study.

PMID- 7643029
TI  - The standard angle between the longitudinal axis of the ear and the bridge of the
      nose in Thai women.
AB  - A photographic technique was used to measure the angle between the longitudinal
      axis of the ear and the bridge of the nose of 619 Thai women, aged 15 to 25
      years, from all 6 regions of Thailand, and that of beautiful Thai women subjects
      to determine the most desirable angle. This was done to test the validity of the
      hypothesis which postulates that the longitudinal axis of the ear should be
      parallel to the bridge of the nose, and to compare this angle with those
      determined from studies in other countries to determine national differences. It
      was also desired to determine the angle that looks best and appears to be most
      aesthetically pleasing from evaluation of questionnaires. It was found that the
      longitudinal axis of the ear is not parallel to the bridge of the nose, and that
      the angle in Thai women should be 19.3 +/- 5.5 degrees to provide both proper and
      aesthetic placement of the reconstructed ear. There is no statistically
      significance difference in this angle among the population of all regions of
      Thailand and the beautiful subjects. However. Thais, Japanese and Americans have
      different angles, so it appears that each nationality has its own normal value
      for this angle.

PMID- 7643030
TI  - Comparative study between scrotal physical examination and scrotal
      ultrasonography in the detection of varicocele in men with infertility.
AB  - From September 1989 to March 1991, we evaluated 110 men from our infertility
      clinic to determine the correlation between scrotal physical examination and
      scrotal ultrasonography in the detection of varicocele in men seeking clinical
      evaluation for infertility, depicting scrotal ultrasound as the gold standard. Of
      110 men with infertility, clinically palpable varicocele was found in 40 patients
      (36.36%). Fifteen were of grade 1, nineteen of grade 2 and four of grade 3. Of
      these 40 patients, 32 (80%) had left sided varicocele 2 (5%) had right sided
      varicocele and the remaining 6 patients (15%) had bilateral varicoceles. Of the
      40 patients with clinically palpable varicocele, 34 (85%) had the diagnosis
      confirmed by scrotal ultrasound. Of these 34 patients who had varicocele
      diagnosed by scrotal ultrasound, 17 (50%) had varicocele on the left side, 1
      (2.94%) had varicocele on the right side and the remaining 16 patients (47.07%)
      had bilateral varicoceles. Seventy patients in whom initial scrotal physical
      examination failed to detect varicocele, 12 (17.14%) were found to have
      varicocele by scrotal ultrasound, all of which were on the left side. This group
      of patients was classified as subclinical varicocele. Statistical analysis
      revealed that scrotal physical examination in the detection of clinical
      varicocele has sensitivity of 73.90 per cent, specificity of 90.60 per cent and
      positive predictive value of 85.00 per cent with negative predictive value of
      82.80 per cent.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7643031
TI  - Interstitial lung diseases in children: a review.
AB  - Interstitial lung diseases (ILD) are disorders of the lower respiratory tract,
      characterized by chronic inflammation of the lung parenchyma, varying degree of
      fibrosis, derangement of the alveolar walls and loss of the functional alveolar
      capillary units. ILD are relatively uncommon in children. Most of the
      interstitial lung diseases have no known etiology. In children, common diseases
      associated with ILD include viral respiratory tract infections (RSV,
      parainfluenza, etc.), gastroesophageal reflux, idiopathic pulmonary fibrosis,
      pulmonary hemosiderosis, eosinophilic pneumonia, pneumonitis associated with
      AIDS, etc. Chronic inflammation of the alveoli (alveolitis), the initial injury
      in ILD, and several mediators released from inflammatory cells (eosinophils,
      neutrophils and macrophages) can cause fibrosis and derangement of alveolar
      walls. Dyspnea and a non-productive cough are the cardinal symptoms of ILD. Other
      findings include chest pain, hemoptysis and weight loss. Clubbing of fingers
      occur in approximately 50 per cent of cases. Diagnosis is based on a combination
      of history, clinical findings, radiographic findings, pulmonary function tests
      and histologic findings. Open lung biopsy has been very helpful in providing
      information regarding the extent and nature of the damage, prognosis and response
      to therapy. There are 3 main aspects in the treatment of ILD. The most important
      step is to identify and eliminate the cause. The second is suppression of the
      inflammation. The third is supportive and symptomatic treatment. Corticosteroids
      are the drugs commonly used for suppression of inflammation. Immunosuppressive
      drugs (azathioprine, cyclophosphamide) have also been tried. Lung transplantation
      and heart transplantation have been successfully achieved in selected patients.
      The results of therapy should be regularly monitored by clinical symptoms, chest
      radiographs and serial pulmonary function studies.

PMID- 7643032
TI  - Direct approach to a traumatic intracavernous internal carotid artery aneurysm: a
      case report.
AB  - A traumatic intracavernous ICA aneurysm is a rare complication of head injury
      with skull base fracture. The hallmark of this condition is delayed, repeated,
      progressively worse and eventually fatal epistaxis. Inadequate treatment and
      delayed diagnosis are the major contributors to the high mortality. After
      epistaxis is controlled by anterior and posterior nasal packing, the patient
      should be investigated with carotid angiography and cross-flow study. In general,
      the acceptable procedure for this lesion is the trapping procedure by internal
      carotid artery ligation at the neck and clipping just proximal to the origin of
      the opthalmic artery, or by detachable balloon occlusion. However, Dolenc's
      technique of direct approach to cavernous sinus lesions makes it feasible to clip
      directly, as in this reported case.

PMID- 7643033
TI  - Cholesterol ester storage disease: a reported case.
AB  - Cholesterol ester storage disease is a rare autosomal recessive disease which is
      characterized by accumulation of cholesterol esters and triglycerides in the
      hepatocytes and other tissues. A 5-year and 4-month old Thai female with
      hepatosplenomegaly and hypercholesterolemia was diagnosed to have this disease by
      light and electron microscopic studies of the liver tissue from open biopsy.
      Early diagnosis and treatment with appropriate drug can help the patient by
      delaying the consequent complications. Genetic counselling and simplified
      explanation of the disease are a benefit to the patient's family.

PMID- 7643034
TI  - Distribution of injected dexamethasone from the buccal vestibule of the rat
      mandible.
AB  - Thirty-six Sprague-Dawley rats were divided into three groups of 12. Group 1 was
      a control, whereas group 2 had the dental pulp of the first mandibular molar
      acutely exposed, and group 3 had dental pulp exposure for 10 days. All animals
      were injected with 125I-labeled dexamethasone phosphate into the right mandibular
      vestibule. Each group of 12 was divided into subgroups of 4 and sacrificed at 1,
      2, or 4 h. The soft tissue on the buccal side and the mandible with the molars
      were collected and the radioactivity determined. Dexamethasone was absorbed from
      the injection site and distributed to the ipsilateral mandible and to the
      contralateral muscle and bone similarly, regardless of the treatment. Results
      also indicate a possible osseous affinity for this steroid, which could be
      beneficial in relieving the pain of intraosseous endodontic flare-ups.

PMID- 7643035
TI  - An ultrastructural study of the smear layer: comparative aspects using secondary
      electron image and backscattered electron image.
AB  - The aim of this investigation was to study the influence of three irrigation
      procedures on the composition, structure, and aspect of the smear layer within
      root canals. Three homogeneous groups were prepared without irrigation, with
      physiological serum, or with Dakin (dilute, neutral solution of sodium
      hypochlorite). Root canals were instrumented with Rispi Reamers mounted on a
      counterangle Giromatic. The irrigating solution was delivered with an endodontic
      irrigation needle. Modifications were observed by scanning electron microscope
      using secondary electron imaging and backscattered electron imaging.
      Instrumentation without irrigation produced a very thick smear layer that
      appeared in backscattered electron imaging as a compact assembly or organic and
      inorganic components. Instrumentation using Dakin produced canal walls that were
      less smeared, and the pockets of debris remaining were smaller in size than when
      using physiological serum. When the root canals were irrigated, the smear layer
      appeared as a double layer, one superficial and the other deep. The layers were
      predominantly inorganic with Dakin.

PMID- 7643036
TI  - Influence of apical enlargement on bacterial infection during treatment of apical
      periodontitis.
AB  - This study sought to evaluate the influence of apical enlargement and 1-wk
      calcium hydroxide dressing on bacterial infection of root canals. Sixty single
      rooted teeth were used. Half of these teeth were prepared to a size 25 file and
      the other half to a size 40 file. Then the root canals were dressed with calcium
      hydroxide for 1 wk. Bacterial sampling showed significant reduction of bacterial
      growth during the treatment. No statistically significant difference was noted
      between the size 25 and 40 file groups after instrumentation, and after 1-wk
      calcium hydroxide dressing.

PMID- 7643037
TI  - Evaluation of the bond strength of dentin bonding agents used to seal resected
      root apices.
AB  - A number of improved dentin bonding agents have recently become available, but
      have not been evaluated on apical radicular dentin. The purpose of this study was
      to compare the tensile bond strengths of four adhesive resins on resected root
      ends before and after blood contamination. Forty single-rooted human incisors
      were cleaned and shaped and obturated. The apical 3 mm was then resected at a 45
      degree angle, bonded, and tested for tensile bond strengths using an Instron
      machine. The bonding systems evaluated included Prisma Universal Bond 3,
      Scotchbond MultiPurpose Dental Adhesive, Amalgambond, and All Bond 2. All bonding
      systems were then covered with Prisma APH light-cure composite resin. Results
      indicated that the bond strengths of the blood contaminated groups were
      significantly less than those of the control groups, except in the case of
      Amalgambond where no significant difference was noted. When the surface was
      contaminated with blood, Prisma Universal Bond 3 had significantly lower bond
      strengths, whereas Amalgambond had significantly higher bond strengths than the
      other subgroups.

PMID- 7643038
TI  - Interpretation of endodontic file lengths using RadioVisiography.
AB  - The purpose of this investigation was to compare RadioVisioGraphy (RVG) imaging
      with conventional radiography in determining endodontic file length adjustment.
      Human cadaver sections with first or second molars were used. Files were inserted
      into canals at randomly selected lengths, from 4 mm short of the radiographic
      apex to 3 mm beyond. Radiographs and RVG images were evaluated to determine the
      adjustment needed to place the file 0.5 mm from the radiographic apex. Results
      showed no significant difference in the ability of endodontists to make accurate
      file length adjustments using conventional radiography versus RVG. In this study,
      it was found that: (a) accurate file length adjustments can be made from an image
      two times larger than the actual tooth; (b) RVG is not significantly better than
      conventional radiography; and (c) if both methods are available, RVG is preferred
      because of the significant reduction in radiation dose.

PMID- 7643039
TI  - Effects of different pH values of citric acid solutions on the calcium and
      phosphorus contents of human root dentin.
AB  - In a group of mandibular incisors, the calcium and phosphorus contents of the
      cervical, middle, and apical thirds of the roots were determined using an
      electron microprobe analyzer, before and after treatment with citric acid
      solutions of different concentrations. The treated surfaces were examined using a
      scanning electron microscope. The relative calcium and phosphorus loss values
      obtained from the samples treated with pH 0.8, 1.1, 1.3, 1.5, and 1.7 solutions
      were significantly different from those obtained in the control group. The
      demineralizing effect of the pH 0.8 and pH 1.3 solutions was the same, with both
      of these being less effective than the pH 1.1 solution.

PMID- 7643040
TI  - Microleakage of retrograde root fillings: assessment using a novel measurement
      system.
AB  - In the past, measurement of microleakage has been based on measurement of dye or
      radioactive isotope penetration. A method has been developed to allow electronic
      monitoring of microflow in the same specimen over a period of time. This method
      was used to compare previously reported retrograde materials with an
      amalgam/sealer combination. The material that performed best was amalgam/sealer,
      particularly in the first week. The role of cavity varnish in limiting leakage
      has been controversial, and the results in the present study do not indicate any
      significant benefit. The range of leakage measured for specimens in the same
      group suggests that in vivo the expected leakage could be considerable for the
      materials tested and that small differences in experimental leakage between
      groups may not have any practical significance.

PMID- 7643041
TI  - Hazards of laser smoke during endodontic therapy.
AB  - The purpose of this study was to evaluate the potential for spreading bacterial
      contamination from the root canal to the patient and the dental team via the
      smoke produced by the laser. Five extracted teeth were deliberately inoculated
      with a specific strain of Escherichia coli. The canals were subjected to an agron
      laser. The smoke plume was captured and cultured. All of the cultures were
      positive for growth of the E. coli used. It was concluded that the laser smoke
      does present a hazard of bacterial dissemination and that precautions must be
      taken to protect against spreading infections when using lasers in the root
      canal.

PMID- 7643042
TI  - Endodontic treatment of a "very particular" maxillary central incisor.
AB  - Maxillary central incisor teeth can vary dramatically in their external and
      internal anatomy. Endodontic treatment of a most unusual four-canal central
      incisor with resorption is described and healing is demonstrated.

PMID- 7643043
TI  - Endodontic treatment of mandibular molars with concrescence.
AB  - Endodontic treatment of a permanent mandibular first molar and a second molar
      presumably joined by cementum is presented. This case illustrates the difficulty
      in interpreting the vitality testing in such a situation. It also suggests
      possible irreversible pulp injury of a vital healthy tooth caused by extension of
      the inflammatory periapical pathosis of the adjacent tooth.

PMID- 7643044
TI  - Covert orienting biases in scene-based reference frames: orientation priming and
      visual field differences.
AB  - Performance advantages for stimuli presented in the right versus the left visual
      field have been found in a variety of attentional tasks. Such advantages were
      exploited in the present set of studies to examine orientation priming and
      directional biases in retinotopic and scene-based spatial coordinates. The
      results demonstrate that directional biases occur within spatial coordinates
      across orientation transformations that dissociate retinotopic from scene-based
      visual half fields. The results are discussed concerning the representation of
      spatial maps in higher visual analysis, the role of spatial coordinates in
      guiding covert orienting, and methods of presenting stimuli in the right or left
      visual field to test for functional hemispheric asymmetries.

PMID- 7643045
TI  - The locus of visual-motor learning at the task or manipulator level: implications
      from intermanual transfer.
AB  - To assess the functional locus of visual-motor learning, the computational
      concepts of "task level" programming (determination of the trajectory of a hand
      during arm reaching in the Cartesian coordinates) and "manipulator level"
      programming (determination of the joint coordinates) was adopted. Because the
      former is likely to be hand nonspecific and the latter is hand specific, it is
      assumed that learning at the task level should be transferred to the unpracticed
      hand, whereas that at the manipulator level it should not. Under this assumption,
      the paradigm of intermanual transfer was used in an aiming task under rotated
      visual feedback. Nearly 100% intermanual transfer from the practiced hand to the
      unpracticed hand in the performance time of aiming was found, concluding that the
      locus of visual-motor learning should be at the task level rather than at the
      manipulator level.

PMID- 7643046
TI  - Psychophysical assessment of toddlers' ability to cope with slopes.
AB  - This research examined how infants in early stages of walking determine whether a
      hill is safe or risky for locomotion. A psychophysical staircase procedure
      provided estimates of infants' physical ability to walk up and down slopes (2
      degrees to 36 degrees), and a "go ration" indexed the accuracy of their
      perceptual judgments. On average, perceptual judgments were scaled to walking
      ability on slopes. Children walked on safe slopes and balked on risky ones. For
      ascent, perceptual judgments were related to length of walking experience and
      walking skill on flat ground. Better walkers were also better perceivers. For
      descent, judgments neatly mirrored exploratory activity. Better perceivers
      explored hills more efficiently by hesitating, touching, and testing different
      positions on hills around the limits of their physical ability.

PMID- 7643047
TI  - Auditory stream segregation by musical timbre: effects of static and dynamic
      acoustic attributes.
AB  - Two experiments examined the influence of timbre on auditory stream segregation.
      In experiment 1, listeners heard sequences of orchestral tones equated for pitch
      and loudness, and they rated how strongly the instruments segregated.
      Multidimensional scaling analyses of these ratings revealed that segregation was
      based on the static and dynamic acoustic attributes that influenced similarity
      judgements in a previous experiment (P Iverson & CL Krumhansl, 1993). In
      Experiment 2, listeners heard interleaved melodies and tried to recognize the
      melodies played by a target timbre. The results extended the findings of
      Experiment 1 to tones varying pitch. Auditory stream segregation appears to be
      influenced by gross differences in static spectra and by dynamic attributes,
      including attack duration and spectral flux. These findings support a gestalt
      explanation of stream segregation and provide evidence against peripheral channel
      model.

PMID- 7643048
TI  - Activation of lexical codes for simultaneously presented words: modulation by
      attention and pathway strength.
AB  - Horizontal and vertical stings were presented in a "crosswords" format within
      left or right visual fields. Distractor strings were varied to examine the extent
      to which prelexical, orthographic-phonological, and semantic codes are activated
      for words not focally attended. The results supported 2 predictions of the
      pathway strength model of attentional modulation (JD Cohen, K Dunbar & JL
      McClelland, 1990). First, distractor influences were greater when participants
      attended to the weaker (ie, vertical) item and ignored the stronger (ie,
      horizontal) string, than vice versa. Second, distractors similar to the target
      facilitated, whereas dissimilar distractors interfered with, pronunciation
      responses. It is concluded that spatial attention can modulate word recognition
      processes, and that some interesting questions emerge when one abandons the
      assumptions of serial, noninteractive word recognition processes.

PMID- 7643049
TI  - Detection of surfaces in structure from motion.
AB  - In 3 experiments the authors examined the effects of surface shape on the
      detection of surfaces in structure from motion displays. In experiment 1 they
      found the number of points necessary to distinguish simple quadratic surfaces
      from points randomly placed in a volume to be low, in the range of 4-6 points. In
      experiment 2 they found that a hyperbolic shape is harder to detect than an arch
      or parabolic shape and that more curved shapes are easier to detect than less
      curved shapes. In experiment 3 they found that detection of sinusoidal shapes
      increases with increasing amplitude and decreasing frequency, confirming previous
      results with motion parallax displays. This pattern of results is consistent with
      a model in which triangular surface patches are fit through adjacent triples of
      points and displays with smaller mean orientation change between neighboring
      triangles are judged to be surface displays.

PMID- 7643050
TI  - Young infants' retention of information about bisyllabic utterances.
AB  - This study examined 2-to 3 month-olds' representations of bisyllables. In 3
      experiments, infants were familiarized with sets of bisyllables that either did
      or did not share a common consonant-vowel (CV) syllable. In Experiment 1, infants
      detected the presence of a new bisyllable in the test phase except when it shared
      a common initial CV syllable. a modified version of the high-amplitude sucking
      (HAS) procedure, incorporating a 2-min delay period, tested infants' retention of
      information about bisyllables in the remaining 2 experiments. In Experiment 2,
      infants were significantly more likely to retain information about bisyllables
      that shared the same initial CV syllable. Finally, the authors investigated
      whether infants simply benefited from the presence of 2 common phonetic segments,
      regardless of whether these came from the same cv syllable. The results showed
      that CV syllable organization is important in infants' ability to encode and
      retain information about bisyllables.

PMID- 7643051
TI  - Stimulus-response compatibility and automatic response activation: evidence from
      psychophysiological studies.
AB  - Effects of dimensional overlap between stimuli and responses on partial response
      activation were investigated within a priming paradigm with the help of event
      related potentials. The likely position of a target stimulus (requiring a left or
      a right reaction) was indicated by an arrow precue. To test whether automatic
      response activation processes are triggered by the cue, the lateralized readiness
      potential was computed. It was found that responses congruent to the direction of
      the cue were activated about 200 ms after cue onset. This early process was
      unaffected by specific cue-response contingencies and was completely missing when
      a nonspatial (color) cue was used. A second response activation phase was
      observed, which was partially controlled by specific response instructions and
      subjective expectancies. It is concluded that when stimuli and responses overlap
      with respect to spatial attributes, automatic response activation process are
      triggered, which may later be replaced by the activation of an expected response.

PMID- 7643052
TI  - Stimulus-response compatibility with relevant and irrelevant stimulus dimensions
      that do and do not overlap with the response.
AB  - Five experiments were conducted using 4- and 6-choice stimulus-response
      compatibility tasks with graphic and alphabetic stimuli, and keypress and verbal
      responses. A comparison of performance with compatible, incompatible, and neutral
      conditions shows that when a stimulus set is perceptually, conceptually, or
      structurally similar to a response set, (a) mean reaction times (RTs) are faster
      when individual stimuli and responses match than when they do not match, (b) this
      is true whether the stimulus and response sets are similar on relevant or
      irrelevant dimensions, (c) this "compatibility effect" is greater when the
      dimensions are relevant than when they are irrelevant, and (d) whether the
      dimensions are relevant or irrelevant, the faster RTs are due to a facilitative
      process and the slower RTs to an interfering process. These results are accounted
      for by the dimensional overlap model.

PMID- 7643053
TI  - Influence of case type, word frequency, and exposure duration on visual word
      recognition.
AB  - The authors report 4 lexical decision experiments in which case type, word
      frequency, and exposure duration were varied. These data indicated that there is
      a larger mixed-case disadvantage for nonwords than for words for longer duration
      presentations of targets. However, when targets were presented for 100 ms
      (followed by a postdisplay pattern mask), a larger mixed-case disadvantage
      occurred for words than for nonwords. For word frequency, the data from
      Experiments 1, 2, and 3 revealed a slightly larger mixed- case disadvantage for
      higher frequency words than for lower frequency words. (There was additivity
      between word frequency and case type for experiment 4.) These results are
      consistent with a holistically biased, hybrid model of visual word recognition
      but inconsistent with analytically biased, hybrid models of word recognition,
      such as the process model (Besner & Johnston, 1989) and the interactive
      activation model (McClelland & Rumelhart, 1981).

PMID- 7643054
TI  - Cost-effectiveness of Haemophilus influenzae type b conjugate vaccine program in
      Florida.
AB  - Introduction of Haemophilus influenzae type b (Hib) vaccine has significantly
      decreased this disease's incidence in childhood. The cost-effectiveness and
      economic impact of the Hib immunization program in Florida were investigated and
      three periods compared: I = 1984-1988; II = 1989-1990; and III = 1991-1992. The
      cost per year of Hib disease in Period I was $27.48 million while that in Periods
      II and III was $15.95 million and $.88 million respectively. The total savings in
      millions were: Periods I and II = $11.53; Periods II and III = $11.07; and
      Periods I and III = $22.6. The greatest saving was realized between Periods I and
      III because of the initiation of immunization with the Hib vaccine starting at
      two months of age during Period III. Hib immunization is cost-effective and
      significant savings would more than pay for the cost of the program.

PMID- 7643055
TI  - Roles of physicians, genetic counselors, and nurses in the genetic counseling
      process.
AB  - A self-administered questionnaire was mailed to 325 genetic counseling
      professionals in the southeastern United States and 204 (63%) completed it. Among
      those responding, 32% held master's degrees in genetic counseling, 30% M.D.
      degrees, 23% degrees in nursing, and 3% master's degrees in social work. While
      genetic counseling typically involves team effort, members were generally unclear
      regarding their roles in the process. Respondents rarely referred their clients
      to social workers but believe they should. Most did not believe that master's
      trained genetic counselors should be the only health professional who provide
      counseling. The respondents strongly supported goals that dealt with the
      educative aspect of counseling and protection of patient autonomy.

PMID- 7643056
TI  - Chlamydia trachomatis. A trojan horse.
AB  - Chlamydia trachomatis is a prevalent and virulent pathogen in the genital tract
      of sexually active women. The sequelae are diverse and represent a significant
      source of morbidity. The Centers for Disease Control estimates 4 million new
      cases annually, making it the most prevalent sexually transmitted disease in the
      United States. Several risk factors are well-defined and the pathophysiology has
      become better understood, helping to improve the body of data concerning
      sequelae. Newer diagnostic methods, such as gene probes, ELISA, and PCR, are now
      available to aid in detection. Novel treatment regimens have been developed to
      improve eradication of the infection and compliance. There are still questions
      regarding this pathogen and its interaction with other lower genital tract
      pathogens. Improved detection, reporting and appropriate treatment can reduce the
      effect of Chlamydial infections on reproductive capacity.

PMID- 7643057
TI  - Physician extenders.

PMID- 7643058
TI  - Bilateral deselection.

PMID- 7643059
TI  - Home health care.

PMID- 7643060
TI  - Psychiatric morbidity associated with motor vehicle accidents.
AB  - The primary purpose of this report was to determine the extent of psychiatric
      morbidity and comorbidity among a sample of recent victims of motor vehicle
      accidents (MVAs) in comparison to a nonaccident control population. Victims of
      recent MVAs (N = 158), who sought medical attention as a result of the MVA, were
      assessed in a University-based research clinic, 1 to 4 months after the accident
      for acute psychiatric and psychosocial consequences as well as for pre-MVA
      psychopathology using structured clinical interviews (Clinician-Administered PTSD
      Scale, SCID, SCID-II, LIFE Base). Age- and gender-matched controls (N = 93) who
      had had no MVAs in the past year served as controls. Sixty-two MVA victims
      (39.2%) met DSM-III-R criteria for posttraumatic stress disorder (PTSD), and 55
      met DSM-IV criteria. The MVA victims who met the criteria for PTSD were more
      subjectively distressed and had more impairment in role function (performance at
      work/school/homemaking, relationships with family or friends) than the MVA
      victims who did not meet the PTSD criteria or the controls. A high percentage
      (53%) of the MVA-PTSD group also met the criteria for current major depression,
      with most of that developing after the MVA. A prior history of major depression
      appears to be a risk factor for developing PTSD after an MVA (p = .0004): 50% of
      MVA victims who developed PTSD had a history of previous major depression, as
      compared with 23% of those with a less severe reaction to the MVA. A prior
      history of PTSD from earlier trauma also is associated with developing PTSD or a
      subsyndromal form of it (25.2%) (p = .0012). Personal injury MVAs exact
      substantial psychosocial costs on the victims. Early intervention, especially in
      vulnerable populations, might prevent some of this.

PMID- 7643061
TI  - Depression and the experience and expression of anger in marital and other
      relationships.
AB  - In prior research using trait self-report measures, depression has been linked to
      elevated anger experience and anger suppression, whereas observational studies of
      marital interactions reveal high rates of overt anger expression by depressed
      people. This study tested whether the key distinction between these contradictory
      lines of research is a) target of anger expression (people in general versus
      spouse) or b) method of measurement (self-report versus behavioral observation).
      Depressed patients (N = 33) scored significantly higher than did nondepressed
      controls (N = 41) on self-report measures of anger and anger suppression
      regardless of whether the target of anger was the spouse or others. Group
      differences were nonsignificant on anger expression. Thus, it appears that the
      critical feature of studies linking depression with heightened anger expression
      may be their use of behavioral observations rather than their specific focus on
      the marital relationship.

PMID- 7643062
TI  - Monoamine oxidase inhibitors in posttraumatic stress disorder. Promise and
      problems in Indochinese survivors of trauma.
AB  - An examination of the available literature supports the efficacy of monoamine
      oxidase inhibitors (MAOIs) in treating posttraumatic stress disorder (PTSD). This
      effect may or may not be independent of the response of symptoms of major
      depression; there is suggestive but inconclusive evidence supporting both.
      Additionally, evidence is accumulating that the avoidance symptoms of PTSD
      respond less reliably to chemotherapy and may be less important in characterizing
      this entity than the intrusive recollection of traumatic events and hyperarousal
      symptoms; clinical cases from the Indochinese Psychiatry Clinic support this
      assertion. Concerns about the clinical use of MAOIs in the Indochinese population
      are raised, as is work in progress on reversible inhibitors of monoamine oxidase
      A that may effectively address those concerns. A recent suggestion that PTSD may
      be one of a family of affective disorders is discussed in light of the treatment
      effects of MAOIs and clinical experience with Southeast Asian survivors of mass
      violence.

PMID- 7643063
TI  - Defense style in personality disorders. An empirical study.
AB  - Do patients with DSM-III-R axis II diagnoses use defenses thought to be specific
      to personality disorders, such as omnipotence, devaluation, splitting, and
      projective identification? Thirty-one psychiatric outpatients with personality
      disorders, 42 neurotic outpatients, and 353 community controls completed the 88
      item Defense Style Questionnaire. Factor analysis yielded four factors (defense
      styles). One of them consisted of omnipotence, devaluation, splitting, denial,
      isolation, and projective identification, defenses considered as typically
      "borderline" (Cronbach's alpha = .72). The personality disorder group scored
      significantly higher on the borderline defense style than did the other two
      groups. The other defense styles (mature, immature, and neurotic) did not
      differentiate between the patient groups, but the mature and immature styles did
      distinguish between patients and healthy controls.

PMID- 7643064
TI  - Gender differences in schizophrenia.
AB  - In an assessment of gender differences in schizophrenia, 85 outpatients (53 men
      and 32 women) with schizophrenia were evaluated for illness history, symptom
      severity, IQ, neurocognitive status, cerebral volume loss, and cortical
      asymmetry. Social functioning was assessed using marital status, independent
      living skills, and employment status. Significant gender differences were found,
      as women were on lower doses of neuroleptic medications and more frequently met
      criteria for paranoid and disorganized subtypes of schizophrenia than men. Women
      also were better educated and more often married, living independently, and
      employed. No gender differences were found in present age, symptom severity,
      neurocognitive functioning, or clinical magnetic resonance imaging scan readings.
      Our findings suggest that women may experience less of the adverse interpersonal
      psychosocial consequences of schizophrenia than men, even when symptom and
      neurocognitive status is equivalent between groups. However, more extensive
      investigations are warranted to better understand the role of pathophysiological
      or social mechanisms in gender differences.

PMID- 7643065
TI  - Race in the treatment of homeless mentally ill veterans.
AB  - A multi-site descriptive outcome study examined differences between black and
      white veterans in admission characteristics, program participation, and outcomes
      following an episode of treatment in a Veterans Affairs residential program for
      homeless veterans with psychiatric and substance abuse problems. Admission,
      discharge, and 6-month and 12-month postdischarge follow-up data were collected
      on 119 black and 144 white veterans admitted to the Domiciliary Care for Homeless
      Veterans Program at three sites. Chi-square tests and t-tests were used to
      identify differences between racial groups at admission. Factorial repeated
      measures analysis of covariance was then used to identify differences between
      black and white veterans in improvement, controlling for differences that were
      significant at the time of admission. On admission, blacks were younger and had
      more problems with drugs and violent behavior, but were less likely than whites
      to have clinical diagnoses of alcohol abuse or a serious psychiatric disorder,
      and had fewer suicide attempts. They also had more social contacts and had more
      frequently experienced a recent disruption in an important relationship. Few
      differences were found between the two racial groups in measures of program
      participation. One year after discharge, both black and white veterans had
      improved in virtually all domains. Black veterans showed greater improvement in
      medical symptomatology, social contacts, and violence, while white veterans
      showed a greater increase in outpatient health service use. While both black and
      white veterans benefitted from participation in residential treatment, the data
      suggest that blacks were more likely to re-establish previously disrupted social
      ties while whites increased their involvement in the VA health care system.

PMID- 7643066
TI  - The heterogeneity of temporal lobe epilepsy. Neurology, neuropsychology, and
      psychiatry.
AB  - The present paper introduces the reader to the behavioral variability of patients
      with temporal lobe epilepsy. The neurobiological variability is evidenced by
      reviewing neurological, neurophysiological, and neuropsychological
      investigations. The behavioral variability of persons affected by epilepsy with a
      temporal focus is proposed to be an expression of the neurobiological complexity
      of temporal lobe epilepsy. The aim of this paper is to encourage endeavors in
      behavioral taxonomy. Efforts to foster homogeneity through improved
      classification are considered fundamental in behavioral science and should be
      applied to epilepsy. The achievement of a behavioral taxonomy may help in both
      understanding the mechanism(s) of these behavioral disorders and targeting more
      specific treatments.

PMID- 7643067
TI  - Magnetic resonance imaging correlates of psychosis in Alzheimer's disease.

PMID- 7643068
TI  - The Charles Bonnet syndrome (pseudohallucinations) in an AIDS patient with
      cytomegalovirus retinitis.

PMID- 7643069
TI  - Mnemonics for ten DSM-IV disorders.

PMID- 7643071
TI  - Voltage-gated currents and firing properties of embryonic Drosophila neurons
      grown in a chemically defined medium.
AB  - This study reports the composition of a chemically defined medium (DDM1) that
      supports the survival and differentiation of neurons in dissociated cell cultures
      prepared from midgastrula stage Drosophila embryos. Cells with neuronal
      morphology that stain with a neural-specific marker are clearly differentiated by
      1 day in vitro and can be maintained in culture for up to 2 weeks. Although the
      whole cell capacitance measurements from neurons grown in DDM1 were 5- to 10-fold
      larger than those of neurons grown in a conventional serum-supplemented medium,
      the potassium current densities were similar in the two growth conditions. A
      small but significant increase in the sodium current density was observed in the
      neurons grown in DDM1 compared with those in serum-supplemented medium. The
      majority of neurons grown in DDM1 fired either single or trains of action
      potentials in response to injection of depolarizing current. Contributing to the
      observed heterogeneity in the firing properties between individual neurons grown
      in DDM1 was heterogeneity in the levels of expression and gating properties of
      voltage-dependent sodium, calcium, and potassium currents. The ability of
      embryonic Drosophila neurons to differentiate in a chemically defined medium and
      the fact that they are amenable to both voltage-clamp and current-clamp analysis
      makes this system well suited to studies aimed at understanding the mechanisms
      regulating expression of ion channels involved in electrical excitability.

PMID- 7643070
TI  - In situ hybridization reveals transient laminin B-chain expression by individual
      glial and muscle cells in embryonic leech central nervous system.
AB  - Laminin, which strongly stimulates axon outgrowth in vitro, appears transiently
      within the central nervous system (CNS) in embryos. After CNS injury, laminin
      reportedly reappears along axonal pathways only in animal species in which
      central axon regeneration is successful, including the leech Hirudo medicinalis.
      Although glia have been suspected of making CNS laminin, in adult leeches glia
      are not required for laminin synthesis and evidently microglia, not present in
      the early embryo, produce laminin. To determine which embryonic cells make
      laminin, a 1.2 kb DNA fragment of leech laminin B1 chain, with homology to
      Drosophila, human, and mouse B1 laminins and rat S laminin, was isolated using
      reverse-transcription and degenerate polymerase chain reaction (PCR) cloning. In
      situ hybridization revealed that laminin expression began before embryonic day 8,
      and by days 8 and 9 it was seen in paired CNS muscle cells. By late day 9, the
      two neuropil glial cells began to express laminin. Lucifer Yellow dye was
      injected intracellularly and muscle cells stimulated to contract, confirming the
      identities of muscle and glial cells. Packet glial cells began to express B1
      laminin by embryonic day 12. By day 15, the cells of the perineurial sheath
      expressed B1 laminin, whereas it was no longer detectable in CNS muscle and glia.
      The results agree with published immunohistochemistry showing laminin within the
      CNS among growing axons by day 8, and only later in the perineurial sheath, by
      which time laminin disappears from within the CNS. Therefore, different cells
      synthesize laminin in the embryo and during repair in adults.

PMID- 7643072
TI  - Seasonal variation in hippocampal volume in a food-storing bird, the black-capped
      chickadee.
AB  - Black-capped chickadees (Parus atricapillus) in upstate New York show a peak in
      food-hoarding intensity in October. We caught chickadees at six different times
      of the year and measured the volume of several brain structures. We found that
      the hippocampal formation, which is involved in spatial memory for cached food
      items, has a larger volume, relative to the rest of the brain, in October than at
      any other time of the year. We conclude that there is an association between the
      intensity of food hoarding and the volume of the hippocampal formation and
      suggest that the enhanced anatomy might be caused by the increased use of spatial
      memory.

PMID- 7643073
TI  - Dividing neuron precursors express neuron-specific tubulin.
AB  - Neuronal differentiation involves specific molecular and morphological changes in
      precursors and results in mature, postmitotic neurons. The expression of neuron
      specific beta tubulin, as detected by the monoclonal antibody TuJ1, begins during
      the period of neurogenesis. Indeed, TuJ1 expression precedes that of the 160 kD
      neurofilament protein in both the central and peripheral nervous systems. In the
      embryonic rat spinal cord, bipolar cells and some mitotic cells in the
      ventricular zone were TuJ1 immunoreactive (IR). Sensory ganglia also contained
      cells with TuJ1-IR mitotic spindles in situ. In embryonic rat sensory and
      sympathetic ganglion cell cultures pulsed with the thymidine analog
      bromodeoxyuridine (BrdU), TuJ1 label was detected in the spindle of mitotic cells
      and in the midbody of cells joined at cytokinesis, indicating that neuron
      specific tubulin expression was initiated during or before the final mitosis of
      neuronal progenitors. Dorsal root ganglion cultures included TuJ1-IR cells with
      several shapes that may reflect morphological transitions, from flattened
      stellate neural crest-like cells to differentiated bipolar neurons. Indeed, the
      presence of flattened TuJ1-IR cells was correlated with neurogenesis. Some
      sympathetic neuron precursors possessed long TuJ1-IR neurites, as well as TuJ1-IR
      spindle microtubules and BrdU-labeled chromosomes, indicating that these
      precursors can possess long processes during metaphase. These results support the
      hypothesis that neuron-specific tubulin expression represents an early molecular
      event in neuronal differentiation exhibited by a wide range of neuronal
      precursors. The cessation of proliferation can occur at different points during
      neuronal differentiation, as TuJ1-IR was detected in cells undergoing mitosis.
      Future studies directed toward understanding the molecules that initiate neuron
      specific tubulin expression may lead to the factors that control the initial
      phases of neuronal differentiation.

PMID- 7643074
TI  - Octopamine mediates rapid stimulation of protein kinase A in the antennal lobe of
      honeybees.
AB  - In the honeybee octopamine mediates mechanisms of arousal that interfere with the
      appetitive proboscis extension response to food-indicating chemosensory stimuli.
      This study demonstrates that injections of octopamine or cyclic adenosine
      monophosphate (cAMP) into the primary chemosensory neuropil of the honeybee, the
      antennal lobe, evokes a rapid and transient activation of cAMP-dependent protein
      kinase (PKA). Other monoamines detectable in the antennal lobe, dopamine and
      serotonin, do not affect the level of PKA activity. Stimulation of the bees'
      antenna with the appetitive stimulus water or sucrose solution in vivo also
      causes a short-term activation of PKA in the antennal lobe. The increased PKA
      activity can be detected immediately (0.5 s) after stimulation but reverts to the
      basal level within 3 s. This effect can be abolished by monoamine depletion with
      reserpine. Since octopamine is the only monoamine that stimulates PKA, it appears
      to mediate the PKA activation after sucrose stimulus and may contribute to the
      processing of this chemosensory input.

PMID- 7643075
TI  - Distribution of androgen receptor immunoreactivity in the spinal cord of wild
      type, androgen-insensitive and gonadectomized male rats.
AB  - The polyclonal antiserum PG21 was used to detect androgen receptor (AR) protein
      in three motoneuronal pools of the male rat lumbar spinal cord. In gonadally
      intact, wild-type males, the spinal nucleus of the bulbocavernosus (SNB),
      dorsolateral nucleus (DLN), and retrodorsolateral nucleus (RDLN) all displayed
      immunolabeling of cell nuclei. The percentage of motoneurons displaying such
      labeling was highest in the SNB and lowest in the RDLN. This pattern of AR
      immunocytochemical labeling agrees well with previous steroid autoradiographic
      studies of androgen accumulation in the rat spinal cord. In contrast, virtually
      no motoneurons in any of the three pools displayed nuclear AR immunostaining in
      long-term gonadectomized males or in gonadally intact males carrying the Tfm
      mutation, which renders the AR incompetent. In gonadectomized males, labeling was
      restored in the SNB and DLN, but not the RDLN, 30 min after an injection of
      replacement testosterone. Eight hours of testosterone exposure restored
      immunolabeling in all three motor nuclei. Apparent cytoplasmic staining was seen
      in SNB motoneurons of untreated castrates and Tfm rats, but not intact rats,
      suggesting that AR residing in the cytoplasm translocates to the nucleus on
      binding to androgen in these motoneurons.

PMID- 7643076
TI  - Calcium transients in growth cones and axons of cultured Helisoma neurons in
      response to conditioning factors.
AB  - Accumulating evidence indicates that cytosolic calcium levels regulate growth
      cone motility and neurite extension. The purpose of this study was to determine
      if intracellular calcium levels also influence the initiation of neurite
      extension induced by growth-promoting factors. An in vitro preparation of
      axotomized neurons that can be maintained in the absence of growth-promoting
      factors was utilized. The distal axons of cultured Helisoma neurons plated into
      defined medium do not extend neurites until they are exposed to Helisoma brain
      conditioned medium. This provided the opportunity to study the intracellular
      changes associated with neurite extension. Cytosolic calcium levels were
      monitored with the calcium-sensitive dye fura 2 at the distal axon. In control
      medium calcium levels in the distal axon were constant. However, transient
      elevations in cytosolic calcium in the axonal growth cone occurred after addition
      of conditioned medium and coincident with the initiation of neurite extension.
      Application of calcium channel blockers showed that the transients resulted from
      calcium influx across the neuronal membrane. The transients, however, were not
      required for neurite extension, although they did influence the rate and extent
      of neurite outgrowth. Simultaneous extracellular patch recordings demonstrated
      that the calcium transients were correlated temporally with an increase in
      rhythmic spontaneous electrical activity of cells, suggesting that conditioned
      medium influences ionic membrane properties of these neurons.

PMID- 7643077
TI  - Early isolation from conspecific song does not affect the normal developmental
      decline of N-methyl-D-aspartate receptor binding in an avian song nucleus.
AB  - Early effects of experience on synaptic reorganization and behavior often involve
      activation of N-methyl-D-aspartate (NMDA) receptors. We have begun to explore the
      role of this glutamate-receptor subtype in the development of learned birdsong.
      Song learning in zebra finches occurs during a restricted period that coincides
      with extensive synaptic reorganization within neural regions controlling song
      behavior. In one brain region necessary for song learning, the lateral
      magnocellular nucleus of the anterior neostriatum (IMAN), NMDA receptor binding
      is twice as high at the onset of song learning as in adulthood. In the present
      study, we used quantitative autoradiography with the noncompetitive NMDA
      antagonist [3H]MK-801 to examine more closely the developmental decline in NMDA
      receptor binding within IMAN and found that it occurred gradually over the period
      of song learning and was not associated with a particular stage of the learning
      process. In addition, early isolation from conspecific song did not affect [3H]MK
      801 binding in IMAN at 30, 60, or 80 days. Since behavioral studies confirmed
      that our isolate rearing conditions extended the sensitive period for song
      learning, we conclude that the normal developmental decline in overall NMDA
      receptor binding within IMAN does not terminate the capacity for song learning.
      Finally, early deafening, which prevents both stages of song learning, also did
      not affect [3H]MK-801 binding in IMAN at 80 days, indicating that the decline in
      NMDA receptor binding occurs in the absence of auditory experiences associated
      with song development.

PMID- 7643078
TI  - Initial sex differences in neuron growth and survival within an avian song
      nucleus develop in the absence of afferent input.
AB  - Only male zebra finches (Poephila guttata) sing, and nuclei implicated in song
      behavior exhibit marked sex differences in neuron number. In the robust nucleus
      of the anterior neostriatum (RA), these sex differences develop because more
      neurons die in young females than in males. However, it is not known whether the
      sexually dimorphic survival of RA neurons is a primary event in sexual
      differentiation or a secondary response to sex differences in the number of cells
      interacting trophically with RA neurons. In particular, since sexual
      differentiation of the RA parallels the development of dimorphisms in the numbers
      of neurons providing afferent input from the lateral magnocellular nucleus of the
      anterior neostriatum (IMAN) and the high vocal center (HVC), it has been
      hypothesized that sex differences in the size of these afferent populations
      trigger differential RA neuron survival and growth. To test this hypothesis, we
      lesioned either the IMAN or both the IMAN and HVC unilaterally in 12-day-old male
      and female zebra finches. Subsequently, RA cell death and RA neuron number and
      size were measured. Unilateral IMAN lesions increased cell death and decreased
      neuron number and size within the ipsilateral RA of both sexes. However, even in
      the IMAN-lesioned hemisphere, these effects were less pronounced in males than in
      females, so that by day 25 the volume, number, and size of neurons were sexually
      dimorphic in both the contralateral and ipsilateral RA. Similarly, the absence of
      both IMAN and HVC afferents did not prevent the emergence of sex differences in
      the number and size of RA neurons by 25 days posthatching. We conclude that these
      sex differences within the RA are not a secondary response to dimorphisms in the
      numbers of IMAN or HVC neurons providing afferent input.

PMID- 7643079
TI  - Astroglia demonstrate regional differences in their ability to maintain primary
      dendritic outgrowth from mouse cortical neurons in vitro.
AB  - To determine whether glia from different regions of the central nervous system
      (CNS) initiate or maintain primary dendritic growth, embryonic day 18 mouse
      cortical neurons were co-cultured with rat (postnatal day 4) astroglial cells
      derived from retina, spinal cord, mesencephalon, striatum, olfactory bulb,
      retina, and cortex. Axon and dendrite outgrowth from isolated neurons was
      quantified using morphological and immunohistochemical techniques at 18 h and 1,
      3, and 5 days in vitro. Neurons initially extend the same number of neurites,
      regardless of the source of glial monolayer; however, glial cells differ in their
      ability to maintain primary dendrites. Homotypic cortical astrocytes maintain the
      greatest number of primary dendrites. Glia derived from the olfactory bulb and
      retina maintained intermediate numbers of dendrites, whereas only a small number
      of primary dendrites were maintained by glia derived from striatum, spinal cord,
      or mesencephalon. Longer axons were initially observed from neurons grown on glia
      that did not maintain dendrite number. Axonal length, however, was similar on the
      various monolayers after 5 days in vitro. Neurons that were grown in media
      conditioned by either mesencephalic or cortical glia for the first 24 h followed
      by culture media from glia of the alternate source for 4 days in vitro confirmed
      that glia maintained, rather than initiated, the outgrowth of the primary
      dendritic arbor. These results indicate that glial cells derived from various CNS
      regions differ in their ability to maintain the primary dendritic arbor from
      mouse cortical neurons in vitro.

PMID- 7643080
TI  - Analysis of the proenkephalin second messenger-inducible enhancer in rat striatal
      cultures.
AB  - We have previously shown that in cell extracts from rat striatum, cyclic AMP
      response element (CRE) binding protein (CREB), rather than AP-1 proteins,
      preferentially interacts with the CRE-2 element of the proenkephalin second
      messenger-inducible enhancer, even under conditions in which AP-1 proteins are
      highly induced. Here we use primary striatal cultures to permit a more detailed
      analysis of CRE-2 function and protein binding in relevant neural cell types. By
      transfection we find that in primary striatal cultures, as in transformed cell
      lines, the CRE-1 and CRE-2 elements are required for significant induction by
      cyclic AMP. We report that cyclic AMP induction of the proenkephalin gene in
      striatal cultures is protein synthesis independent, excluding a role for newly
      synthesized proteins like c-Fos. We also show that cyclic AMP induces CREB
      phosphorylation and that phosphorylated CREB interacts strongly with CRE-2 and
      weakly with CRE-1. The predominant protein bound to CRE-1 is not CREB, however,
      and remains to be identified. Despite some prior predictions, we do not find a
      role for c-Fos in cyclic AMP regulation of proenkephalin gene expression in
      neurons.

PMID- 7643081
TI  - Epidermal growth factor and basic fibroblast growth factor protect dopaminergic
      neurons from glutamate toxicity in culture.
AB  - In this report we characterize the toxicity of the excitatory amino acid L
      glutamate with respect to dopaminergic neurons cultured from embryonic rat
      mesencephalon. We also demonstrate that two growth factors, epidermal growth
      factor (EGF) and basic fibroblast growth factor (bFGF), can protect these neurons
      from damage. Micromolar concentrations of L-glutamate, as well as agonists that
      specifically activate N-methyl-D-aspartate (NMDA) and non-NMDA receptors, are all
      toxic to dopamine neurons in a concentration-dependent manner, as reflected by
      decreases in high-affinity dopamine uptake and confirmed by decreases in numbers
      of tyrosine hydroxylase-immunoreactive neurons. Although the non-NMDA receptor
      antagonist 6-cyano-7-nitroquinoxaline-2,3-dione could attenuate the effects of
      quisqualate, treatment with this antagonist could not eliminate the effects of
      glutamate itself. Similarly, (+/-)-2-amino-5-phosphonopentanoic acid was
      effective against NMDA toxicity but could not protect cells from quisqualate
      toxicity. Thus, each type of receptor could mediate neurotoxicity independently
      of the other. The presence of EGF or bFGF in the culture medium conferred a
      relative resistance of dopaminergic neurons to glutamate and quisqualate
      neurotoxicity by increased glutamate transport. However, treatment of the
      cultures with L-trans-pyrrolidine-2,4-dicarboxylic acid, an inhibitor of
      glutamate transport, attenuated but did not eliminate the protective effects of
      both growth factors against glutamate toxicity. When cultures were incubated with
      conditioned medium from growth factor-treated cultures, neuroprotection was also
      achieved. These results suggest that both EGF and bFGF can protect neurons from
      neurotoxicity in culture by increasing the capacity of the culture for glutamate
      uptake as well as by the secretion of soluble factors into the medium.

PMID- 7643082
TI  - Induction of neuronal apoptosis by excitotoxins associated with long-lasting
      increase of 12-O-tetradecanoylphorbol 13-acetate-responsive element-binding
      activity.
AB  - We show that excitotoxic cell death, which is associated with pathological
      neurodegenerative processes, can display morphological and biochemical features
      characteristic of apoptosis, a mode of cell death typical of physiological
      neuronal elimination during development. Cortical neurons cultured in the absence
      of serum, stimulated with NMDA, glutamate, or quisqualate after 3-5 days in
      vitro, showed significant degeneration. This death was blocked by 1 microM MK
      801, indicating that it was mediated by the activation of NMDA receptors. Dying
      cells displayed an apoptotic morphology, characterized by cytoplasm and chromatin
      condensation. No internucleosomal DNA degradation was observed, confirming that
      morphological changes of apoptosis can be dissociated from DNA laddering.
      Inhibitors of protein or RNA synthesis abolished cell death, and the protective
      effect of cycloheximide was similar when the drug was applied 2 h before or 8 h
      after glutamate. These experiments suggest the participation of active gene
      transcription in the mechanism of death. We thus analyzed the modulation of
      transcription factors in dying cells using electrophoretic mobility shift assays.
      The level of factors binding to the 12-O-tetradecanoylphorbol 13-acetate
      responsive element (TRE) displayed a late and sustained increase preceding
      neuronal death, which was not found for factors complexing the Sp1 P, Oct, and
      USF binding sites. These results raise the possibility that apoptosis is one of
      the mechanisms of death in the pathologies linked to excitotoxicity and that
      activation of TRE-binding factors could play a role in these processes.

PMID- 7643083
TI  - Microglial cathepsin B: an immunological examination of cellular and secreted
      species.
AB  - The cysteine proteinase cathepsin B (CB) was isolated from immortalized murine BV
      2 microglial cells and examined via sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis and immunoblotting to establish physicochemical properties of CB
      from what is generally considered the resident CNS macrophage. Microglial
      proteases have been implicated in several pathological processes occurring in the
      CNS, including neurodegeneration. Murine microglial CB was observed to consist of
      two major single-chain species of 32 and 34 kDa, with pls of 5.5-5.2 and 5.1-4.5,
      respectively. In addition, a minor 24-kDa CB species was also observed in some
      microglial preparations. The major CB isozymes in microglia differed from those
      observed in murine liver and brain, which consisted of both single- and double
      chain CB variants of 31 and 24-25 kDa/5 kDa, respectively, with pl values of 5.5
      4.5. A microglial pro-CB of 37 kDa was also isolated, which could be processed to
      the 34-kDa single-chain CB species. Cystatin was observed to prevent pro-CB
      processing, whereas E-64 and leupeptin were only partially inhibitory. The 37-kDa
      pro-CB species was observed to undergo processing into the 34-kDa CB species when
      incubated at pH 5.5 but remained stable with respect to molecular mass when
      incubated at pH 7.0. In contrast, the 34-kDa single-chain CB species was observed
      to autodegrade when incubated at pH 7.0, whereas incubation at pH 5.5 did not
      affect the integrity of the species as monitored by immunoblotting. Both pro-CB
      and 32-kDa single-chain CB species were observed extracellularly following
      lipopolysaccharide activation of BV-2 microglial cells.

PMID- 7643084
TI  - Cytochalasins protect hippocampal neurons against amyloid beta-peptide toxicity:
      evidence that actin depolymerization suppresses Ca2+ influx.
AB  - Increasing data suggest that the amyloid beta-peptide (A beta), which accumulates
      in the brains of Alzheimer's victims, plays a role in promoting neuronal
      degeneration. Cell culture studies have shown that A beta can be neurotoxic and
      recent findings suggest that the mechanism involves destabilization of cellular
      calcium homeostasis. We now report that cytochalasin D, a compound that
      depolymerizes actin microfilaments selectively, protects cultured rat hippocampal
      neurons against A beta neurotoxicity. Cytochalasin D was effective at
      concentrations that depolymerized actin (10-100 nM). The elevation of [Ca2+]i
      induced by A beta, and the enhancement of [Ca2+]i responses to glutamate in
      neurons exposed to A beta, were markedly attenuated in neurons pretreated with
      cytochalasin D. The protective effect of cytochalasin D appeared to result from a
      specific effect on actin filaments and reduction in calcium influx, because
      cytochalasin E, another actin filament-disrupting agent, also protected neurons
      against A beta toxicity; the microtubule-disrupting agent colchicine was
      ineffective; cytochalasin D did not protect neurons against the toxicity of
      hydrogen peroxide. These findings suggest that actin filaments play a role in
      modulating [Ca2+]i responses to neurotoxic insults and that depolymerization of
      actin can protect neurons against insults relevant to the pathogenesis of
      Alzheimer's disease.

PMID- 7643085
TI  - Characterization of the excitoprotective actions of N-methyl-D-aspartate in
      cultured cerebellar granule neurons.
AB  - Exposure of cultured cerebellar granule neurons to subtoxic concentrations of N
      methyl-D-aspartate (NMDA) has been shown previously to result in a
      neuroprotective state, as measured by subsequent exposure to toxic concentrations
      of glutamate. In the present study, we have further characterized the
      excitoprotective actions of NMDA in these neurons. NMDA-induced excitoprotection
      was concentration dependent (EC50 approximately 30 microM) and time dependent,
      with maximal protection observed following 16 h of preexposure to NMDA. NMDA
      induced excitoprotection did not require continuous exposure to NMDA, as a 4-h
      preincubation was sufficient to induce full excitoprotection when measured 8 h
      later. Maximal protection was manifest as a "right shift" in the concentration
      response relationship for glutamate toxicity of approximately three orders of
      magnitude (EC50 approximately 30 microM in untreated neurons compared with > or =
      50 mM in NMDA-treated neurons). After removal of NMDA, complete reversal of the
      excitoprotective state was observed by 48 h (t1/2 approximately 24 h). The
      ability of NMDA to induce excitoprotection was observed in neurons maintained for
      up to 14 days in vitro (DIV) [postnatal day (PND) 22], but was absent at 21 and
      32 DIV (PND 29-40), despite little to no difference in the toxicity of glutamate
      at any DIV examined. Preexposure of cerebellar granule neurons to a maximally
      excitoprotective concentration of NMDA (50 microM) failed to alter the density of
      NMDA receptors measured by the specific binding of [3H]MK-801.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7643088
TI  - Nitric oxide-induced [3H] GABA release from cerebral cortical neurons is mediated
      by peroxynitrite.
AB  - The functional significance of peroxynitrite in the release of [3H]GABA induced
      by nitric oxide (NO) liberated from NO generators was investigated using cerebral
      cortical neurons in primary culture. NO generators such as sodium nitroprusside
      (SNP) and S-nitroso-N-acetylpenicillamine (SNAP) increased [3H] GABA release in a
      dose-dependent manner. These increases in [3H]-GABA release were significantly
      inhibited by hemoglobin, indicating that those NO generators evoke the release of
      [3H] GABA by the formation of NO. Two types of superoxide scavengers, Cu2+/Zn2+
      superoxide dismutase and ceruloplasmin, significantly reduced the increase in
      [3H]-GABA release induced by both SNP and SNAP, which assumes that NO requires
      superoxide to induce [3H]-GABA release from the neurons. In addition, synthesized
      peroxynitrite induced a dose-dependent increase in [3H]-GABA release from the
      neurons. These results indicate that NO-induced [3H] GABA release is mediated by
      peroxynitrite formed by the reaction of NO with superoxide.

PMID- 7643087
TI  - Glutamate receptor-mediated calcium surges in neurons derived from P19 cells.
AB  - Retinoic acid-treated murine P19 embryonal carcinoma cells differentiate into
      cells with neuronal morphology that display typical neuronal markers. In this
      study, the presence of glutamate receptors linked to Ca(2+)-signaling mechanisms
      on these neurons was demonstrated by testing the effects of glutamate agonists
      and antagonists on the intracellular calcium ion concentration ([Ca2+]i).
      Glutamate (1 mM) induced either sustained or transient increases in [Ca2+]i. The
      sustained glutamate-induced increase in [Ca2+]i was mimicked by NMDA (40 microM).
      The NMDA-triggered [Ca2+]i response was abolished by incubating the cells in
      Ca(2+)-free medium or by pretreating them with Mg2+ (2 mM) or MK-801 (0.1
      microM). These responses were unaffected by the non-NMDA antagonist CNQX (10
      microM), but they required glycine (3-30 microM). Kainate (40 microM) and AMPA
      (40 microM) did not affect [Ca2+]i. Without external Ca2+, glutamate triggered
      transient, sometimes oscillating, increases in [Ca2+]i. These responses were
      mimicked by the metabotropic agonist trans-(1S, 3R)-1-amino-1,3
      cyclopentanedicarboxylic acid (300 microM). These results suggest that neurons
      derived from P19 embryonal carcinoma cells have NMDA and metabotropic, but not
      AMPA/kainate receptors, which are linked to Ca(2+)-signaling mechanisms. These
      cells could provide a consistent and reproducible model with which to study
      neuronal differentiation, neurotoxicity, and glutamate receptor-signaling
      mechanisms.

PMID- 7643086
TI  - The mammalian pineal expresses the cone but not the rod cyclic GMP
      phosphodiesterase.
AB  - To determine the presence of cone or rod cyclic GMP phosphodiesterase (EC
      3.1.4.17) in the mammalian pineal, extracts from adult rat and bovine pineals
      were injected onto a Mono Q anion-exchange HPLC column and eluted with an NaCl
      linear gradient. Fractions were immunoadsorbed with monoclonal antibodies
      specific to rod and cone phosphodiesterases (ROS-1) and to calmodulin
      phosphodiesterase complexes (ACC). Profiles were assayed with 10 mumol/L
      [3H]cyclic GMP in the presence of calcium-calmodulin, histone, or trypsin. Rat
      and bovine pineals displayed a single peak of activity recognized by ROS-1, which
      corresponded to the activity of the cone but not to the rod in bovine retina. ROS
      1 immunoadsorbed approximately 80% of the activity in the 60-day-old rat pineal
      but only 26% of the activity in bovine pineal. ACC immunoadsorbed the remaining
      activity in both species. Western blot analysis of rat pineal extracts revealed
      three polypeptides of approximately 87, 15, and 10 kDa when probed with a
      rod/cone phosphodiesterase-specific antiserum. The specific activity of the cone
      like phosphodiesterase in 10-day-old rat pineals was twice that of this isozyme
      in the bovine retina and 150 times that in the bovine pineal. The specific
      activity of phosphodiesterase in rat pineals decreased with age. We conclude that
      an enzyme with biochemical and antigenic characteristics similar to cone, but
      distinct from rod phosphodiesterase, is present in bovine and rat pineals.

PMID- 7643089
TI  - Astroglial phosphoinositide hydrolysis during combined glucose-oxygen
      deprivation: role of the metabotropic glutamate receptor.
AB  - Phosphatidylinositol bisphosphate hydrolysis, leading to the production of myo
      inositol trisphosphate and diacylglycerol, may play a significant role in the
      pathogenesis of hypoxic-ischemic brain injury. We used tritiated myo-inositol
      phosphate (3H-IP) accumulation as a means to quantitate phosphoinositide
      hydrolysis in pre-labeled astroglial cultures subjected to combined glucose
      oxygen deprivation. Astroglial cultures exposed to combined glucose-oxygen
      deprivation had significantly greater 3H-IP accumulation compared with cultures
      exposed to control conditions. To delineate the role of the metabotropic
      glutamate receptor in astroglial phosphoinositide hydrolysis during combined
      glucose-oxygen deprivation, we studied the effects of two metabotropic glutamate
      receptor antagonists, 2-amino-3-phosphonopropionic acid and (+)-methyl-4
      carboxyphenylglycine. 2-Amino-3-phosphonopropionic acid attenuated the
      accumulation of 3H-IP during combined glucose-oxygen deprivation but acted as an
      agonist under control conditions. (+)-Methyl-4-carboxyphenylglycine had no effect
      on 3H-IP accumulation during combined glucose-oxygen deprivation or under control
      conditions. These results suggest that activation of astroglial phosphoinositide
      hydrolysis during combined glucose-oxygen deprivation may be mediated, at least
      in part, by the metabotropic glutamate receptor.

PMID- 7643090
TI  - D2 receptor antagonists do not modify guanine nucleotide-sensitive interactions
      between dopamine and D1 dopamine receptors under in vitro conditions.
AB  - This study investigated possible D1/D2 interactions in rat and bovine striatal
      tissue by examining the effects of D2 antagonists on the action of dopamine at D1
      dopamine receptors. In addition, the extent to which D2 antagonists may induce an
      agonist low-affinity state of the D1 receptor was evaluated in comparison with
      the effects of the guanine nucleotide analogue 5'-guanylyl-imidodiphosphate
      [Gpp(NH)p]. In saturation experiments dopamine caused a dose-dependent decrease
      in rat striatal and bovine caudate D1 receptor density. This effect of dopamine,
      which has been shown to be sensitive to Gpp (NH)p, was not altered by
      pretreatment with either of the selective D2 antagonists eticlopride (200 nM) or
      domperidone (200 nM). Results from displacement experiments show that the
      affinity of dopamine for D1 receptors, and the proportion of receptors in an
      agonist high-affinity state, are reduced by Gpp(NH)p (100 microM) but not by
      eticlopride. A molar excess of dopamine (100 microM) promotes the dissociation of
      (+/-)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7-o l
      ([3H]SCH 23390) from rat striatal D1 receptors at a rate that is significantly
      slower than when dissociation is initiated using 1 microM piflutixol. After
      pretreament with Gpp(NH)p, [3H]SCH 23390 dissociation induced by dopamine
      occurred at an even slower rate. Pretreatment with eticlopride had no effect on
      the dopamine-induced rate of [3H]SCH 23390 dissociation. These results indicate
      that all experimental approaches detected dopamine effects at D1 receptors that
      are Gpp(NH)p sensitive and D2 antagonist insensitive and provide no evidence to
      support a D1/D2 link operating at the receptor level.

PMID- 7643091
TI  - Differential calcitonin gene-related peptide (CGRP) and amylin binding sites in
      nucleus accumbens and lung: potential models for studying CGRP/amylin receptor
      subtypes.
AB  - Calcitonin gene-related peptide (CGRP), a 37-amino-acid peptide, is a member of a
      small family of peptides including amylin or islet amyloid polypeptide and salmon
      calcitonin. These related peptides have been shown to display similar effects on
      in vitro and in vivo carbohydrate metabolism. The present study was initiated to
      identify and characterize the binding sites for these peptides in lung and
      nucleus accumbens membranes prepared from pig and guinea pig. Both tissues in
      either species displayed high-affinity (2-[125I]iodohistidyl10)humanCGRP alpha
      ([125I]hCGRP alpha) binding (IC50 = 0.4-7.7 nM), which was displaced by hCGRP8-37
      alpha with equally high affinity (IC50 = 0.4-7.3 nM). High-affinity binding for
      [125I]Bolton-Hunter human amylin ([125I]BH-h-amylin) was also observed in these
      tissues (IC50 = 0.2-6.0 nM). In membranes from the nucleus accumbens of both
      species, salmon calcitonin competed for amylin binding sites with high affinity
      (IC50 = 0.1 nM) but was poor in competing for amylin binding in lung membranes.
      Rat amylin8-37 competed for [125I]hCGRP alpha binding with higher affinity (IC50
      = 5.4 nM) compared with [125I]BH-h-amylin binding (IC50 = 200 nM) in porcine
      nucleus accumbens, whereas in guinea pig nucleus accumbens, the IC50 values for
      rat amylin8-37 were 117 and 12 nM against [125I]hCGRP alpha and [125I]BH-h
      amylin, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7643092
TI  - Serotonergic regulation of acetylcholine release in rat frontal cortex.
AB  - The extent to which serotonin regulates the activity of cortically projecting
      cholinergic neurons was studied using in vivo microdialysis to monitor
      interstitial concentrations of acetylcholine in the frontal cortex of freely
      moving rats. Systemic administration of the serotonin release-inducing agent
      fenfluramine (3 or 10 mg/kg, i.p.) increased acetylcholine release by 110-130%.
      The fenfluramine-induced increase in acetylcholine release was significantly
      attenuated by pretreatment with the selective serotonin uptake inhibitor
      fluoxetine (10 mg/kg, i.p.). Pretreatment with the selective dopamine D1 receptor
      antagonist SCH-23390 (0.3 mg/kg, s.c.) failed to prevent the fenfluramine-induced
      increase in acetylcholine release. In contrast, the serotonin 5-HT2A receptor
      antagonist ketanserin (5 mg/kg, i.p.) blocked fenfluramine-induced increases in
      acetylcholine release. In contrast to previous studies that have concluded that
      serotonin has inhibitory actions on cortical acetylcholine release, the present
      results indicate that fenfluramine increases cortical acetylcholine release in
      vivo by its ability to enhance serotonin transmission and that serotonin produces
      these effects at least in part via actions at serotonin 5-HT2A receptors.

PMID- 7643093
TI  - Modulation of intracellular cyclic AMP levels by different human dopamine D4
      receptor variants.
AB  - To investigate whether polymorphic forms of the human dopamine D4 receptor have
      different functional characteristics, we have stably expressed cDNAs of the D4.2,
      D4.4, and D4.7 isoforms in several cell lines. Chinese hamster ovary CHO-K1 cell
      lines expressing D4 receptor variants displayed pharmacological profiles that
      were in close agreement with previous data from transiently expressed D4
      receptors in COS-7 cells. Dopamine stimulation of the D4 receptors resulted in a
      concentration-dependent inhibition of the forskolin-stimulated cyclic AMP (cAMP)
      levels. The potency of dopamine to inhibit cAMP formation was about twofold
      reduced for D4.7 (EC50 of approximately 37 nM) compared with the D4.2 and D4.4
      variants (EC50 of approximately 16 nM). Antagonists block the dopamine-mediated
      inhibition of cAMP formation with a rank order of potency of emonapride >
      haloperidol = clozapine >> raclopride. There was no obvious correlation between
      the efficacy of inhibition of forskolin-stimulated cAMP levels and the D4
      subtypes. Dopamine could completely reverse prostaglandin E2-stimulated cAMP
      levels for all three D4 receptor variants. Deletion of the repeat sequence does
      not affect functional activity of the receptor. The data presented indicate that
      the polymorphic repeat sequence causes only small changes in the ability of the
      D4 receptor to block cAMP production in CHO cells.

PMID- 7643094
TI  - Concentrations of 3,4-dihydroxyphenylalanine and catecholamines and metabolites
      in brain in an anhepatic model of hepatic encephalopathy.
AB  - Alterations in the catecholaminergic neurotransmitter systems have been shown to
      occur in hepatic failure and may contribute to development of hepatic
      encephalopathy. In the present study we used the rat after complete hepatectomy
      as a model for study of changes that occur in brain in acute liver failure. We
      attempted to identify processes in the synthesis, storage, and metabolism of
      catecholamine neurotransmitters that might be changed during liver failure by
      measuring levels of, together with those of norepinephrine and dopamine, the
      precursor (3,4-dihydroxyphenylalanine) and the neuronal metabolites of dopamine
      and norepinephrine (3,4-dihydroxyphenylacetic acid and 3,4-dihydroxyphenylglycol,
      respectively) in different regions of brains of control rats and of rats after
      hepatectomy. We found that in most brain regions of hepatectomized rats there
      were increases in the concentration of 3,4-dihydroxyphenylalanine or of dopamine
      but decreases in the concentrations of norepinephrine or of 3,4
      dihydroxyphenylglycol. The particulate/supernatant ratios of catecholamines are
      indices of retention of neurotransmitters in storage sites. These ratios were not
      different in brain regions between control rats and hepatectomized rats,
      suggesting that vesicular retention of catecholamines in brain was not impaired
      after hepatectomy. The data suggest that inhibition of dopamine-beta-hydroxylase
      might be a characteristic of hepatic failure.

PMID- 7643095
TI  - Comparison of the neurochemical and behavioral effects resulting from the
      inhibition of kynurenine hydroxylase and/or kynureninase.
AB  - Several kynurenine analogues were synthesized and tested as inhibitors of the
      enzymes kynurenine hydroxylase and/or kynureninase with the aim of identifying
      new compounds able to inhibit the synthesis of quinolinic acid (an endogenous
      excitotoxin) and to increase that of kynurenic acid, an endogenous antagonist of
      ionotropic glutamate receptors. Among these analogues, we selected m
      nitrobenzoylalanine (mNBA) as an inhibitor of kynurenine hydroxylase and o
      methoxybenzoylalanine (oMBA) as an inhibitor of kynureninase. When administered
      to rats, mNBA was more potent than oMBA in increasing the content of kynurenine
      and of kynurenic acid in the brain, blood, liver, and kidney. This confirms that
      hydroxylation is the main pathway of kynurenine metabolism. Both mNBA and oMBA
      (50-400 mg/kg i.p.) increased the concentration of kynurenate in hippocampal
      extracellular spaces (as measured with a microdialysis technique) and, when
      simultaneously injected, their effects were additive. This biochemical effect was
      associated with a decrease in locomotor activity in rats and with a protection of
      audiogenic convulsions in DBA/2 mice. In conclusion, the results of the present
      experiments indicate the possibility of increasing the neosynthesis of kynurenic
      acid by inhibiting the enzymes that metabolize kynurenine to 3-hydroxykynurenine
      or to anthranilic acid. The increased synthesis of kynurenate is associated with
      behavioral effects such as sedation and protection from seizures, which suggests
      a functional antagonism of the excitatory amino acid receptors.

PMID- 7643096
TI  - Selective inhibition of the tricarboxylic acid cycle of GABAergic neurons with 3
      nitropropionic acid in vivo.
AB  - The effects of 3-nitropropionic acid (3-NPA), an inhibitor of succinate
      dehydrogenase, on cerebral metabolism were investigated in mice by NMR
      spectroscopy. 3-NPA, 180 mg/kg, caused a dramatic buildup of succinate. Succinate
      was labeled 5.5 times better from [1-(13)C]glucose than from [2-(13)C]acetate,
      showing a predominantly neuronal accumulation. [1-(13)C]Glucose labeled GABA in
      the C-2 position only, compatible with inhibition of the tricarboxylic acid (TCA)
      cycle associated with GABA formation, at the level of succinate dehydrogenase.
      Aspartate was not labeled by [1-(13)C]glucose in 3-NPA-intoxicated animals. In
      contrast, [1-(13)C]glucose labeled glutamate in the C-2, C-3, and C-4 positions
      showing uninhibited cycling of label in the TCA cycle associated with the large,
      neuronal pool of glutamate. The labeling of glutamine, and hence GABA, from [2
      (13)C]acetate showed that the TCA cycle of glial cells was unaffected by 3-NPA
      and that transfer of glutamine from glia to neurons took place during 3-NPA
      intoxication. The high 13C enrichment of the C-2 position of glutamine from [1
      (13)C]glucose showed that pyruvate carboxylation was active in glia during 3-NPA
      intoxication. These findings suggest that 3-NPA in the initial phase of
      intoxication fairly selectively inhibited the TCA cycle of GABAergic neurons;
      whereas the TCA cycle of glia remained uninhibited as did the TCA cycle
      associated with the large neuronal pool of glutamate, which includes
      glutamatergic neurons. This may help explain why the caudoputamen, which is
      especially rich in GABAergic neurons, selectively undergoes degeneration both in
      humans and animals intoxicated with 3-NPA.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7643097
TI  - Age-dependent neurotoxicity of striatal lesions produced by aminooxyacetic acid:
      quantitative in vitro 1H NMR spectroscopic studies.
AB  - Aminooxyacetic acid, a potent inhibitor of the mitochondrial malate-aspartate
      shunt, was used to assess the role of mitochondrial energy metabolism in damaged
      brain of rats of different age groups. Three age groups--juvenile (< 1 month),
      young adult (3-4 months), and adult (7 months)--were subjected to examine the age
      related aminooxyacetic acid effect. We measured the absolute concentrations of
      metabolites in perchloric acid extracts of rat striatum after intraperitoneal
      administration of aminooxyacetic acid using 1H NMR spectroscopy. Among
      aminooxyacetic acid-treated groups, a twofold increase of GABA concentration was
      observed in juveniles and young adults, and a threefold elevation of GABA level
      was observed in adults, whereas there were no significant differences of alanine
      and glutamate levels in all three aminooxyacetic acid-treated groups as compared
      with the age-matched controls. Statistically significant decreases of N
      acetylaspartate, glutamine, and creatine levels were detected in treated adults.
      A statistically significant elevation of lactate concentration was found in the
      adult treated group. These data have demonstrated that the impairment of energy
      metabolism in rat striatum induced by aminooxyacetic acid can be revealed by
      quantitative in vitro 1H NMR spectroscopy and that aminooxyacetic acid produces
      age-dependent striatal abnormalities.

PMID- 7643098
TI  - Excess extracellular and low intracellular glutamate in poorly differentiating
      wobbler astrocytes and astrocyte recovery in glutamine-depleted culture medium.
AB  - The wobbler mouse develops an inherited motoneuronal degeneration of unknown
      origin in the spinal cord. Primary cultures of adult wobbler spinal cord
      astrocytes display abnormal morphological characteristics with fewer processes
      and paucity of cell-cell contacts. We have searched for a possible involvement of
      glutamate and glutamine intra- and extracellular accumulations in vitro in the
      abnormal differentiation of mutant astrocytes. We have found significantly higher
      glutamate and glutamine concentrations in the culture media of mutant astrocytes
      over a 3-day period compared with normal control astrocytes. Moreover,
      intracellular glutamate concentrations decreased substantially in mutant
      astrocytes, but intracellular glutamine concentrations remained unchanged.
      Furthermore, decreasing initial glutamine concentrations in the culture medium
      (glutamine-depleted medium) led to the recovery of normal extra- and
      intracellular concentrations of glutamate and recovery of quasi-normal
      morphological differentiation and increased cell-cell contacts, leading to an
      essentially normal looking astrocyte network after 3 days of culture. Under these
      conditions, which lead to recovery, the only remaining abnormality was the higher
      glutamine extracellular concentration attained in the originally depleted
      glutamine media. These findings suggest that mechanisms regulating
      glutamate/glutamine synthesis and/or influx/efflux are defective in wobbler
      astrocytes, leading to metabolic imbalance and possible cytotoxic effects
      characterized by disturbed intercellular networks and poor differentiation.

PMID- 7643099
TI  - Relationships of dopamine, cortical oxygen pressure, and hydroxyl radicals in
      brain of newborn piglets during hypoxia and posthypoxic recovery.
AB  - The present study describes the relationships of extracellular striatal dopamine,
      cortical oxygen pressure, and striatal hydroxyl radicals in brain of newborn
      piglets during hypoxia and posthypoxic reoxygenation. Hypoxia was induced by
      reducing the fraction of inspired oxygen (FiO2) from 22% (control) to 7% for 1 h.
      The FiO2 was then returned to the control value and measurements were continued
      for 2 h. Cerebral oxygen pressure was measured by the oxygen dependent quenching
      of phosphorescence and extracellular levels of dopamine, 3,4
      dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and hydroxy radicals
      in the striatum were determined by in vivo microdialysis. Hypoxia decreased the
      cortical oxygen pressure from 47 +/- 2 to 9 +/- 1.3 torr (p < 0.001); the levels
      of extracellular dopamine in the striatum increased to 16,000 +/- 3,270% of
      control (p < 0.01), whereas the levels of DOPAC and HVA decreased to 25.3 +/- 6%
      (p < 0.001) and 36 +/- 5% (p < 0.01) of control, respectively. Compared with
      control, the hydroxyl radical levels at each time point were not significantly
      increased during hypoxia, although the sum of the measured values was
      significantly increased (p < 0.05). During the first 5 min after FiO2 was
      returned to 22%, the cortical oxygen pressure increased to control values and
      stayed at this level for the remainder of the measurement period. The
      extracellular level of dopamine declined to values not statistically different
      from control during 40 min of reoxygenation. During the first 10 min of
      reoxygenation, DOPAC and HVA further decreased and then began to slowly increase.
      By 70 min of reoxygenation, the values were not significantly different from
      control.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7643100
TI  - Influence of selective inhibition of monoamine oxidase A or B on striatal
      metabolism of L-DOPA in hemiparkinsonian rats.
AB  - The effect of selective inhibition of monoamine oxidase (MAO) subtypes A and B on
      striatal metabolism of DOPA to dopamine (DA), 3,4-dihydroxyphenylacetic acid
      (DOPAC), and 4-hydroxy-3-methoxyphenylacetic acid (homovanillic acid; HVA) was
      studied in halothane-anesthetized rats 3 weeks after unilateral 6-hydroxydopamine
      lesion of the substantia nigra. Implantation of bilateral microdialysis probes
      allowed simultaneous quantitation of metabolite production on lesioned and
      control sides. The DOPA was administered as a 15-min bolus of 1 mM solution in
      the striatal microdialysate. Rats were pretreated with the selective MAO-A
      inhibitor clorgyline, or the selective MAO-B inhibitors deprenyl or TVP-101 [2,3
      dihydro-N-2-propynyl-1H-inden-1-amine-(1R)-hydrochloride]. Intrastriatal infusion
      of DOPA caused an increased efflux of DA, DOPAC, and HVA, which was greater on
      the intact side. Clorgyline, but not deprenyl or TVP-101, increased post-DOPA DA
      efflux on both intact and lesioned sides. Clorgyline also caused a marked
      suppression of post-DOPA DOPAC and HVA effluxes, whereas only mild effects were
      produced by the MAO-B inhibitors. There was no evidence for a differential effect
      of MAO-B inhibition on efflux of DA or metabolites in the lesioned as compared
      with the control striatum. The results indicate a major role for MAO-A in DA
      metabolism both intra- and extraneuronally in the rat striatum.

PMID- 7643101
TI  - Selective alterations of extracellular brain amino acids in relation to function
      in experimental portal-systemic encephalopathy: results of an in vivo
      microdialysis study.
AB  - Portal-systemic encephalopathy (PSE) is characterized by neuropsychiatric
      symptoms progressing through stupor and coma. Previous studies in human autopsy
      tissue and in experimental animal models of PSE suggest that alterations in
      levels of brain amino acids may play a role in the pathogenesis of PSE. To assess
      this possibility, levels of amino acids were measured using in vivo cerebral
      microdialysis in frontal cortex of portacaval-shunted rats administered ammonium
      acetate (3.85 mmol/kg, i.p.) to precipitate severe PSE. Sham-operated rats served
      as controls. Portacaval shunting resulted in significant increases of levels of
      extracellular glutamine (threefold, p < 0.001), alanine (38%, p < 0.01),
      aspartate (44%, p < 0.05), phenylalanine (170%, p < 0.001), tyrosine (140%, p <
      0.001), tryptophan (63%, p < 0.001), leucine (75%, p < 0.001), and serine (60%, p
      < 0.001). Administration of ammonium acetate to sham-operated animals led to a
      significant increase in extracellular glutamine and taurine content, but this
      response was absent in shunted rats. The lack of taurine release into
      extracellular fluid following ammonium acetate administration in portacaval
      shunted rats could relate to the phenomenon of brain edema in these animals.
      Ammonium acetate administration resulted in significant increases in the
      extracellular concentrations of phenylalanine and tyrosine in both sham-operated
      and portacaval-shunted rats. Severe PSE was not accompanied by significant
      increases in extracellular fluid concentrations of glutamate, aspartate, GABA,
      tryptophan, leucine, or serine, suggesting that increased spontaneous release of
      these amino acids in cerebral cortex is not implicated in the pathogenesis of
      hepatic coma.

PMID- 7643102
TI  - Differential expression of GABAA/benzodiazepine receptor subunit mRNAs and ligand
      binding sites in mouse cerebellar neurons following in vivo ethanol
      administration: an autoradiographic analysis.
AB  - The gamma-aminobutyric acidA (GABAA)/benzodiazepine (BZ) receptor is a pentamer
      composed of subunits belonging to several classes (alpha 1-6, beta 1-4, gamma 1
      4, delta, and rho 1 and rho 2). In situ hybridization, radioligand
      autoradiography, and immunocytochemistry were used to examine GABAA/BZ receptor
      alpha 1, alpha 6, beta 2, beta 3, and gamma 2 subunit expression in murine
      Purkinje, granule, and deep cerebellar neurons after in vivo ethanol exposure.
      Chronic ethanol treatment resulted in decreased alpha 1 subunit mRNA expression
      in each cell type, whereas the expression of alpha 6 and gamma 2 subunit mRNA
      levels increased; no changes were observed in the expression of beta 2 and beta 3
      subunit mRNA. GABA and BZ agonist binding and antibody staining paralleled the
      changes in mRNA levels. Acute ethanol injection resulted in increased expression
      of alpha 1 and beta 3 mRNAs, whereas levels of alpha 6, beta 2, and gamma 2 mRNAs
      remained stable. Our results indicate that, in cerebellar neurons, the expression
      of specific GABAA/BZ receptor subunit mRNAs, polypeptides, and binding sites is
      independently regulated by in vivo administration of alcohol. The observed
      changes were not restricted to any one cerebellar cell type, because subunit
      expression in Purkinje, granule, and deep cerebellar cells was similarly
      affected.

PMID- 7643103
TI  - Effect of amygdaloid kindling on the content and release of amino acids from the
      amygdaloid complex: in vivo and in vitro studies.
AB  - The tissue content and the interstitial fluid levels of glutamate, aspartate,
      GABA, glutamine, glycine, and serine were studied in amygdaloid-kindled rat
      brain. Interstitial levels were studied in vivo before and during stage 5 full
      limbic seizures using microdialysis. Slices of amygdala from kindled and sham
      operated animals were used to study baseline and KCl-evoked release in vitro. The
      contents of these amino acids were measured in slices of amygdala, hippocampus,
      and cerebral cortex from kindled and sham-operated animals. Kindled brains showed
      two- to threefold higher levels of glutamate, aspartate, and GABA and 12-fold
      higher levels of glutamine than sham-operated controls. Correlating with this,
      interstitial fluid levels of glutamate were two- to threefold higher from kindled
      amygdala than from control both in vivo (microdialysis) and in vitro
      (superfusion). GABA levels in interstitial fluid from kindled amygdala were
      reduced by 67% compared with control amygdala.

PMID- 7643104
TI  - Detection of free radical activity during transient global ischemia and
      recirculation: effects of intraischemic brain temperature modulation.
AB  - To obtain direct evidence of oxygen radical activity in the course of cerebral
      ischemia under different intraischemic temperatures, we used a method based on
      the chemical trapping of hydroxyl radical in the form of the stable adducts 2,3-
      and 2,5-dihydroxybenzoic acid (DHBA) following salicylate administration. Wistar
      rats were subjected to 20 min of global forebrain ischemia by two-vessel
      occlusion plus systemic hypotension (50 mm Hg). Intraischemic striatal
      temperature was maintained as normothermic (37 degrees C), hypothermic (30
      degrees C), or hyperthermic (39 degrees C) but was held at 37 degrees C before
      and following ischemia. Salicylate was administered either systemically (200
      mg/kg, i.p.) or by continuous infusion (5 mM) through a microdialysis probe
      implanted in the striatum. Striatal extracellular fluid was sampled at regular
      intervals before, during, and after ischemia, and levels of 2,3- and 2,5-DHBA
      were assayed by HPLC with electrochemical detection. Following systemic
      administration of salicylate, stable baseline levels of 2,3- and 2,5-DHBA were
      observed before ischemia. During 20 min of normothermic ischemia, a 50% reduction
      in mean levels of both DHBAs was documented, suggesting a baseline level of
      hydroxyl radical that was diminished during ischemia, presumably owing to oxygen
      restriction to tissue at that time. During recirculation, 2,3- and 2,5-DHBA
      levels increased by 2.5- and 2.8-fold, respectively. Levels of 2,3-DHBA remained
      elevated during 1 h of reperfusion, whereas the increase in 2,5-DHBA persisted
      for 2 h. The increases in 2,3- and 2,5-DHBA levels observed following
      hyperthermic ischemia were significantly higher (3.8- and fivefold,
      respectively). In contrast, no significant changes in DHBA levels were observed
      following hypothermic ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7643105
TI  - Activation of mitogen-activated protein kinase in cultured rat hippocampal
      neurons by stimulation of glutamate receptors.
AB  - Mitogen-activated protein kinase (MAP kinase) was activated by stimulation of
      glutamate receptors in cultured rat hippocampal neurons. Ten micromolar glutamate
      maximally stimulated MAP kinase activity, which peaked during 10 min and
      decreased to the basal level within 30 min. Experiments using glutamate receptor
      agonists and antagonists revealed that glutamate stimulated MAP kinase through
      NMDA and metabotropic glutamate receptors but not through non-NMDA receptors.
      Glutamate and its receptor agonists had no apparent effect on MAP kinase
      activation in cultured cortical astrocytes. Addition of calphostin C, a protein
      kinase C (PKC) inhibitor, or down-regulation of PKC activity partly abolished the
      stimulatory effect by glutamate, but the MAP kinase activation by treatment with
      ionomycin, a Ca2+ ionophore, remained intact. Lavendustin A, a tryrosine kinase
      inhibitor, was without effect. In experiments with 32P-labeled hippocampal
      neurons, MAP kinase activation by glutamate was associated with phosphorylation
      of the tyrosine residue located on MAP kinase. However, phosphorylation of Raf-1,
      the c-raf protooncogene product, was not stimulated by treatment with glutamate.
      Our observations suggest that MAP kinase activation through glutamate receptors
      in hippocampal neurons is mediated by both the PKC-dependent and the Ca(2+)
      dependent pathways and that the activation of Raf-1 is not involved.

PMID- 7643106
TI  - Carbohydrate analysis of the B2 bradykinin receptor from rat uterus.
AB  - The B2 bradykinin receptor purified from rat uterus has an apparent molecular
      mass of 81 kDa. This is higher than the value of 42 kDa estimated from the
      sequence data of rat and human B2 receptors. Carbohydrate analysis of the rat B2
      bradykinin receptor indicated that it was a sialoglycoprotein with three N-linked
      complex oligosaccharide side chains. This was consistent with the sequence, which
      has three potential glycosylation sites. The receptor did not appear to possess O
      linked carbohydrate side chains. Removal of the N-linked carbohydrates with endo
      beta-N-acetylglucosaminidase yielded a core protein of 42-44 kDa. The presence of
      these N-linked carbohydrates explains the discrepancy between the molecular size
      of the purified receptor protein and that estimated from the sequence. The
      sequence of the rat receptor suggests an isoelectric point of about pH 7.0, but
      the purified receptor had an isoelectric point of pH 4.5-4.7. Sialic acid
      residues on the N-linked side chains are likely to be responsible for the acidic
      nature of the rat receptor. Carbohydrate does not appear to play a role in ligand
      receptor interactions, as deglycosylation did not alter the affinity of the B2
      bradykinin receptor for bradykinin or the B2-selective antagonist HOE-140.

PMID- 7643108
TI  - Activation of protein kinase C by the capsaicin analogue resiniferatoxin in
      sensory neurones.
AB  - Resiniferatoxin and capsaicin are sensory neurone-specific excitotoxins that
      operate a common cation channel in nociceptors. Resiniferatoxin is structurally
      similar to capsaicin and to phorbol esters. Specific [3H]-resiniferatoxin
      binding, which was detected in the membrane (KD value 1.8 +/- 0.2 nM) but not
      cytosolic fraction of rat dorsal root ganglia, could not be displaced by phorbol
      12,13-dibutyrate. Conversely, resiniferatoxin did not displace [3H]phorbol 12,13
      dibutyrate binding in either the cytosolic or membrane fraction. Resiniferatoxin
      and capsaicin both caused translocation of protein kinase C in dorsal root
      ganglion neurones (EC50 value 18 +/- 3 nM). This translocation was greatly
      reduced but not abolished, in the absence of external Ca2+, suggesting that it
      was secondary to Ca2+ entry. Resiniferatoxin also caused direct activation of a
      Ca(2+)- and lipid-dependent kinase (or kinases) in the cytosolic fraction of
      dorsal root ganglia, at concentrations (100 nM to 10 microM) higher than required
      for displacement of [3H]resiniferatoxin binding or translocation of protein
      kinase C. Capsaicin (up to 10 microM) was unable to mimic this effect. These data
      imply that although resiniferatoxin-induced translocation of protein kinase C in
      dorsal root ganglion neurones was mainly indirect, it also caused direct
      activation of a protein kinase C-like kinase in these cells.

PMID- 7643107
TI  - Histamine-evoked chromaffin cell scinderin redistribution, F-actin disassembly,
      and secretion: in the absence of cortical F-actin disassembly, an increase in
      intracellular Ca2+ fails to trigger exocytosis.
AB  - Histamine is a known chromaffin cell secretagogue that induces Ca(2+) -dependent
      release of catecholamines. However, conflicting evidence exists as to the source
      of Ca2+ utilized in histamine-evoked secretion. Here we report that histamine-H1
      receptor activation induces redistribution of scinderin, a Ca(2+)-dependent F
      actin severing protein, cortical F-actin disassembly, and catecholamine release.
      Histamine evoked similar patterns of distribution of scinderin and filamentous
      actin. The rapid responses to histamine occurred in the absence of extracellular
      Ca2+ and were triggered by release of Ca2+ from intracellular stores. The trigger
      for the release of Ca2+ was inositol 1,4,5-trisphosphate because U-73122, a
      phospholipase C inhibitor, but not its inactive isomer (U-73343), inhibited the
      increases in IP3 and intracellular Ca2+ levels, scinderin redistribution,
      cortical F-actin disassembly, and catecholamine release in response to histamine.
      Thapsigargin, an agent known to mobilize intracellular Ca2+, blocked the rise in
      intracellular Ca2+ concentration, scinderin redistribution, F-actin disassembly,
      and catecholamine secretion in response to histamine. Calphostin C and
      chelerythrine, two inhibitors of protein kinase C, blocked all responses to
      histamine with the exception of the release of Ca2+ from intracellular stores.
      This suggests that protein kinase C is involved in histamine-induced responses.
      The results also show that in the absence of F-actin disassembly, rises in
      intracellular Ca2+ concentration are not by themselves capable of triggering
      catecholamine release.

PMID- 7643109
TI  - Pituitary adenylate cyclase-activating polypeptide (PACAP) stimulates adenylyl
      cyclase and phospholipase C activity in rat cerebellar neuroblasts.
AB  - The presence of receptors for the novel neuropeptide pituitary adenylate cyclase
      activating polypeptide (PACAP) has been recently demonstrated in the external
      granule cell layer of the cerebellum, a germinative matrix that generates the
      majority of cerebellar interneurons. In the present study, we have taken
      advantage of the possibility of obtaining a culture preparation that is greatly
      enriched in immature cerebellar granule cells to investigate the effect of PACAP
      on the adenylyl cyclase and phospholipase C transduction pathways. The two
      molecular forms of PACAP, i.e., 27-(PACAP27) and 38-(PACAP38) amino-acid forms of
      PACAP, induced a dose-dependent stimulation of cyclic AMP production in granule
      cells. The potencies of PACAP27 and PACAP38 were similar (ED50 = 0.12 +/- 0.01
      and 0.23 +/- 0.07 nM, respectively), whereas vasoactive intestinal polypeptide
      (VIP) was approximately 100 times less potent. PACAP27 and PACAP38 also induced a
      dose-dependent stimulation of polyphosphoinositide breakdown (ED50 = 19.1 +/- 6.3
      and 13.4 +/- 6.0 nM, respectively), whereas VIP had no effect on
      polyphosphoinositide metabolism. The effect of PACAP38 on inositol phosphate
      formation was significantly reduced by U-73122 and by pertussis toxin, indicating
      that activation of PACAP receptors causes stimulation of a phospholipase C
      through a pertussis toxin-sensitive G protein. In contrast, forskolin and
      dibutyryl cyclic AMP did not affect PACAP-induced stimulation of inositol
      phosphates. Taken together, the present results demonstrate that PACAP stimulates
      independently the adenylyl cyclase and the phospholipase C transduction pathways
      in immature cerebellar granule cells. These data favor the concept that PACAP may
      play important roles in the control of proliferation and/or differentiation of
      cerebellar neuroblasts.

PMID- 7643110
TI  - Functional importance of the carboxyl tail cysteine residues in the human D1
      dopamine receptor.
AB  - To assess the importance of the cysteine residues Cys347 and Cys351 in the
      carboxylic tail in the human D1 dopamine receptor, seven mutant receptors were
      constructed by PCR. The pharmacological and functional properties of the wild
      type and mutant receptors were assessed following transient expression in COS-7
      cells. Affinities for [3H]SCH 23390 of mutant S347 (Cys347-->Gly), T348 (Tyr348-
      >stop), S351 (Cys351-->Gly), T351 (Cys351-->stop), T352 (Pro352-->stop), and
      S347/S351 (Cys347-->Gly and Cys351-->Gly) were similar to that of wild-type
      receptor, whereas the expression levels were reduced up to 80%. The potency of
      dopaminergic antagonists for these mutant receptors was very similar to that of
      the wild-type receptor. However, mutant T347 (Cys347-->stop) showed a 15-25-fold
      reduced affinity for the antagonists SCH 23390, (+)-butaclamol, and cis
      flupentixol, thus not allowing radioligand analysis. Wild-type and mutant
      receptors responded dose-dependently with similar potency to dopamine and SKF
      38393 with an increased adenylyl cyclase activity. However, mutant receptors with
      the Cys347 residue changed or removed displayed a diminished ability to activate
      adenylyl cyclase. Dopamine preexposure desensitized wild-type and mutant S351
      receptors. However, mutant receptors with Cys347 replaced or the distal part of
      the carboxyl tail removed were unable to desensitize. Thus, Cys347 in the
      cytoplasmic tail of the human D1 dopamine receptor is important for the receptor
      in maintaining the conformation for antagonist binding, to play a crucial role in
      activation of adenylyl cyclase, and to be essential for agonist-induced
      desensitization.

PMID- 7643111
TI  - Calcium and photoentrainment in chick pineal cells revisited: effects of
      caffeine, thapsigargin, EGTA, and light on the melatonin rhythm.
AB  - Chick pineal cells in dispersed cell culture display a persistent,
      photosensitive, circadian rhythm of melatonin production and release. Light
      pulses have at least two distinguishable effects on these cells, i.e., acute
      suppression of melatonin output and phase shifts (entrainment) of the underlying
      circadian pacemaker. Previous results linked calcium influx through voltage
      sensitive calcium channels in the plasma membrane to acute regulation of
      melatonin synthesis but denied a role for such influx in entrainment. Those
      experiments did not, however, address the role of intracellular calcium
      metabolism. Here we describe the effects of pulses of caffeine, thapsigargin, and
      EGTA on the melatonin rhythm, and their interactions with the effects of light
      pulses. Caffeine had two distinguishable effects on these cells, acute
      enhancement of melatonin output (attributable to phosphodiesterase inhibition)
      and phase shifts of the circadian pacemaker with a light-like pattern
      (attributable to effects on intracellular calcium). Phase shifts induced by light
      and caffeine were not additive. Thapsigargin (which specifically blocks the pump
      that replenishes intracellular calcium stores, thereby increasing cytoplasmic
      calcium and depleting intracellular stores) had no phase-shifting effects by
      itself but reduced the size of the phase advances induced by caffeine or light.
      Low calcium solution acutely suppressed melatonin output without inducing phase
      shifts or affecting those induced by caffeine or light. However, addition of EGTA
      (which specifically chelates calcium, thereby lowering cytoplasmic calcium and
      depleting intracellular stores) did reduce the size of phase advances induced by
      caffeine or light, in normal medium or in low calcium solution, without inducing
      a phase shift by itself at that phase. Taken together, these results point toward
      a role for intracellular calcium fluxes in entrainment of the circadian
      pacemaker.

PMID- 7643112
TI  - Evidence for a glutamatergic pathway from the guinea pig auditory cortex to the
      inferior colliculus.
AB  - We attempt to provide evidence that the projection from the guinea pig auditory
      cortex (AC) to the inferior colliculus (IC) may contain glutamatergic or
      GABAergic fibers. Seven days after unilateral AC aspiration, histological studies
      indicated almost complete AC destruction and preterminal degeneration of fibers
      and terminal fields in the dorsal cortex (DCIC), external cortex (ECIC), and
      central nucleus (CNIC) of the IC ipsilateral to the ablated AC. Contralaterally,
      degeneration appeared in the DCIC. AC ablation depressed the electrically evoked
      Ca(2+)-dependent release of D-[3H]aspartate (D-[3H]Asp) in the ipsilateral DCIC,
      ECIC, and CNIC, and D-[3H]Asp uptake in the CNIC. Together with other evidence
      that the corticocollicular pathway is excitatory, these findings suggest that
      this projection may contain glutamatergic and/or aspartatergic (Glu/Asp-ergic)
      fibers. Glutamic acid decarboxylase immunoreactivity was not apparent in presumed
      pyramidal cells of layer V of the AC retrogradely labeled with biotinylated
      dextran injected into the ipsilateral IC. Thus, corticocollicular neurons
      probably do not synthesize GABA and may not be GABAergic. However, AC ablation
      depressed [14C]GABA release from the ipsilateral DCIC and ECIC, and [14C]GABA
      uptake in the DCIC. These findings are consistent with the atrophy or down
      regulation of some subcortical neurons that mediate GABAergic transmission in the
      IC.

PMID- 7643113
TI  - Reconstitution of high-affinity binding of a beta-scorpion toxin to neurotoxin
      receptor site 4 on purified sodium channels.
AB  - Reconstitution of purified sodium channels into phospholipid vesicles restores
      many aspects of sodium channel function including high-affinity neurotoxin
      binding and action at neurotoxin receptor sites 1-3 and 5, but neurotoxin binding
      and action at receptor site 4 has not previously been demonstrated in purified
      and reconstituted preparations. Toxin IV from the venom of the American scorpion
      Centruroides suffusus suffusus (Css IV), a beta-scorpion toxin, shifts the
      voltage dependence of sodium channel activation by binding with high affinity to
      neurotoxin receptor site 4. Sodium channels were purified from rat brain and
      reconstituted into phospholipid vesicles composed of phosphatidylcholine and
      phosphatidylethanolamine (65:35). 125I-Css IV, purified by reversed-phase HPLC,
      bound rapidly and specifically to reconstituted sodium channels. Dissociation of
      the bound toxin was biphasic with half-times of 0.22 min-1 and 0.015 min-1. At
      equilibrium, the toxin bound to two classes of specific high-affinity sites, a
      variable minor class with KD of approximately 0.1 nM and a major class with a KD
      of approximately 5 nM. Approximately 0.8 mol 125I-Css IV was bound per mole of
      reconstituted, right-side-out sodium channels, as assessed from comparison of
      binding of saxitoxin and Css IV. Binding of Css IV was unaffected by membrane
      potential or by neurotoxins that bind at sites 1-3 or 5, consistent with the
      characteristics of binding of beta-scorpion toxins to sodium channels in cells
      and membrane preparations.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7643114
TI  - Selective inhibition of cholesterol biosynthesis in brain cells by squalestatin
      1.
AB  - The effect of squalestatin 1 (SQ) on squalene synthase and other enzymes
      utilizing farnesyl pyrophosphate (F-P-P) as substrate was evaluated by in vitro
      enzymological and in vivo metabolic labeling experiments to determine if the drug
      selectively inhibited cholesterol biosynthesis in brain cells. Direct in vitro
      enzyme studies with membrane fractions from primary cultures of embryonic rat
      brain (IC50 = 37 nM), pig brain (IC50 = 21 nM), and C6 glioma cells (IC50 = 35
      nM) demonstrated that SQ potently inhibited squalene synthase activity but had no
      effect on the long-chain cis-isoprenyltransferase catalyzing the conversion of F
      P-P to polyprenyl pyrophosphate (Poly-P-P), the precursor of dolichyl phosphate
      (Dol-P). SQ also had no effect on F-P-P synthase; the conversion of [3H]F-P-P to
      geranylgeranyl pyrophosphate (GG-P-P) catalyzed by partially purified GG-P-P
      synthase from bovine brain; the enzymatic farnesylation of recombinant H-p21ras
      by rat brain farnesyltransferase; or the enzymatic geranylgeranylation of
      recombinant Rab 1A, catalyzed by rat brain geranylgeranyltransferase. Consistent
      with SQ selectively blocking the synthesis of squalene, when C6 glial cells were
      metabolically labeled with [3H]mevalonolactone, the drug inhibited the
      incorporation of the labeled precursor into squalene and cholesterol (IC50 = 3-5
      microM) but either had no effect or slightly stimulated the labeling of Dol-P,
      ubiquinone (CoQ), and isoprenylated proteins. These results indicate that SQ
      blocks cholesterol biosynthesis in brain cells by selectively inhibiting squalene
      synthase.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7643115
TI  - Spinal cord dynorphin precursor intermediates decline during late gestation.
AB  - This laboratory has previously reported that the maternal opioid analgesia
      associated with pregnancy and parturition is mediated, at least in part, by a
      maternal spinal cord dynorphin/kappa opioid system. This analgesia is accompanied
      by an increase in dynorphin peptides (1-17 and 1-8) in the lumbar spinal cord.
      Levels of trypsin-generated arginine6-leucine-enkephalin (Leu-Enk-Arg)
      immunoreactive determinants were also determined and used to reflect the content
      of dynorphin precursor intermediates. In spinal tissue, the amount of dynorphin A
      (1-17) contained in the form of precursor is, at a minimum, 10-fold higher than
      the content of mature dynorphin A (1-17) or dynorphin (1-8). During gestational
      day 22, the content of dynorphin precursor is reduced significantly
      (approximately 50%). The decline in the magnitude of dynorphin precursor
      intermediates in the spinal cord of pregnant rats vastly exceeds the magnitude of
      increase in the content of dynorphin peptides (1-17 and 1-8). This difference can
      best be explained by postulating a corresponding increase in the rate of release
      of spinal cord dynorphin (1-17). It is suggested that enhanced processing of
      dynorphin precursor intermediates represents the initial biochemical level of
      adaptation of spinal dynorphin neurons to increased demands of pregnancy.

PMID- 7643116
TI  - Regulation of DOPA decarboxylase activity in brain of living rat.
AB  - To test the hypothesis that L-DOPA decarboxylase (DDC) is a regulated enzyme in
      the synthesis of dopamine (DA), we developed a model of the cerebral uptake and
      metabolism of [3H]DOPA. The unidirectional blood-brain clearance of [3H]DOPA
      (K1D) was 0.049 ml g-1 min-1. The relative DDC activity (k3D) was 0.26 min-1 in
      striatum, 0.04 min-1 in hypothalamus, and 0.02 min-1 in hippocampus. In striatum,
      3,4-[3H]dihydroxyphenylacetic acid ([3H]DOPAC) was formed from [3H]DA with a rate
      constant of 0.013 min-1, [3H]homovanillic acid ([3H]HVA) was formed from
      [3H]DOPAC at a rate constant of 0.020 min-1, and [3H]HVA was eliminated from
      brain at a rate constant of 0.037 min-1. Together, these rate constants predicted
      the ratios of endogenous DOPAC and HVA to DA in rat striatum. Pargyline, an
      inhibitor of DA catabolism, substantially reduced the contrast between striatum
      and cortex, in comparison with the contrast seen in autoradiograms of control
      rats. At 30 min and at 4 h after pargyline, k3D was reduced by 50% in striatum
      and olfactory tubercle but was unaffected in hypothalamus, indicating that DDC
      activity is reduced in specific brain regions after monoamine oxidase inhibition.
      Thus, DDC activity may be a regulated step in the synthesis of DA.

PMID- 7643117
TI  - Eukaryotic initiation factor 4E degradation during brain ischemia.
AB  - Suppression of protein synthesis in the brain following an ischemic insult has
      been thought to occur because of inhibition of translation initiation. All
      eukaryotic mRNAs, with the exception of heat-shock transcripts, require the
      activity of eukaryotic initiation factor (eIF) 4E for formation of the
      translation initiation complex, and eIF-4E availability is rate-limiting. The
      response of brain eIF-4E concentration and phosphorylation following decapitation
      ischemia was studied in rat brain homogenates after electrophoresis and western
      blotting with antibodies against eIF-4E and phosphoserine, respectively. There
      was no change in level of eIF-4E after 5 min of ischemia (p = 0.82 vs. time 0),
      but it had decreased 32 (p = 0.01) and 57% (p = 0.006) after 10 and 20 min of
      ischemia, respectively. There was no loss of serine phosphorylation on eIF-4E
      beyond signal loss observed due to degradation of the protein itself (p = 0.31).
      In vitro exposure of eIF-4E to activated mu-calpain resulted in a 50% loss in 10
      min of eIF-4E on western blots. If active eIF-4E is required for translation of
      its own mRNA, degradation of this protein during ischemia, possibly by activated
      mu-calpain, could be a direct mechanism of irreversible neuronal injury, and the
      rate of proteolysis of eIF-4E could place an upper time limit on the maximal
      duration of global brain ischemia compatible with neurologic recovery.

PMID- 7643118
TI  - Opposite effect of protein synthesis inhibitors on potassium deficiency-induced
      apoptotic cell death in immature and mature neuronal cultures.
AB  - Typically, primary cultures of rat cerebellar granule neurons are grown in the
      presence of 25 mM KCl and are considered to mature by approximately 7 days in
      vitro. Potassium deficiency was created by growing the neurons from days 1 to 4
      in the presence of 12.5 mM KCl (immature cultures) or by switching the mature
      neurons grown with 25 mM KCl to 12.5 mM KCl. In both conditions we observed
      neuronal death that bears the signs of apoptosis, i.e., DNA fragmentation
      determined qualitatively by agarose gel electrophoresis of DNA and quantitatively
      by in situ terminal deoxynucleotidyl transferase assay. The protein synthesis
      inhibitors cycloheximide and anisomycin provided neuroprotection in the mature
      cultures but potentiated the toxic effect of KCl deprivation in the immature
      neurons. The results suggest that a prudent use of protein synthesis inhibitors
      is critical in experiments with primary neuronal cultures.

PMID- 7643119
TI  - Coupling of the cloned mu-opioid receptor with the omega-conotoxin-sensitive Ca2+
      current in NG108-15 cells.
AB  - Voltage-dependent Ca2+ currents were measured in NG108-15 neuroblastoma x glioma
      hybrid cells transformed to express the rat mu-opioid receptor by the whole-cell
      configuration of the patch-clamp technique with Ba2+ as charge carrier. A mu
      opioid receptor-selective agonist, [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin caused
      significant inhibition of voltage-dependent Ca2+ currents in mu-receptor
      transformed NG108-15 cells but not in nontransfected or vector-transformed
      control cells. On the other hand, a delta-opioid receptor-selective agonist, [D
      penicillamine2,D-penicillamine5]enkephalin, induced inhibition of voltage
      dependent Ca2+ currents in both control and mu-receptor-transformed cells, which
      is mediated by the delta-opioid receptor expressed endogenously in NG108-15
      cells. The inhibition of voltage-dependent Ca2+ currents induced by [D-Ala2,N-Me
      Phe4,Gly5-ol]enkephalin [D-penicillamine2,D-penicillamine5]enkephalin was reduced
      by pretreatment of the cells with pertussis toxin or omega-contoxin GVIA. These
      results indicate that the mu-opioid receptor expressed from cDNA functionally
      couples with omega-contoxin-sensitive N-type Ca2+ channels through the action of
      pertussis toxin-sensitive G proteins in NG108-15 cells.

PMID- 7643120
TI  - Cortical regulation of subcortical dopamine release: mediation via the ventral
      tegmental area.
AB  - In vivo microdialysis was used to determine the extent to which ionotropic
      glutamate receptors in the ventral tegmental area (VTA) regulate dopamine release
      in the nucleus accumbens. Coapplication of 2-amino-5-phosphonopentanoic acid
      (AP5; 200 microM) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 50 microM) to
      the VTA via reverse dialysis decreased extracellular concentrations of dopamine
      in the nucleus accumbens by approximately 30%. In accordance with previous
      results, electrical stimulation of the prefrontal cortex increased dopamine
      release by 60%. Application of AP5 and CNQX to the VTA during cortical
      stimulation blocked the effect of stimulation on dopamine release. These results
      indicate that ionotropic glutamate receptors in the VTA are critically involved
      in basal and evoked dopamine release in the nucleus accumbens and suggest that a
      glutamatergic projection from the prefrontal cortex regulates the activity of
      dopaminergic neurons in the VTA.

PMID- 7643121
TI  - Poly(ADP-ribose) synthetase activation: an early indicator of neurotoxic DNA
      damage.
AB  - DNA damage activates a nuclear enzyme poly(ADP-ribose) synthetase (PARS) that
      facilitates DNA repair by adding multiple ADP-ribose groups to nuclear proteins
      such as histones and PARS itself. N-Methyl-D-aspartate neurotoxicity may involve
      DNA damage excessively activating PARS to deplete its substrate NAD, as PARS
      inhibitors prevent this toxicity. We now show that PARS is rapidly and markedly
      activated in PC12 cells following treatment with neurotoxic agents, including the
      amyloid beta-protein, hydrogen peroxide, N-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP), and its active metabolite N-methyl-4-phenylpyridine
      (MPP+). With MPP+, PARS activity is increased fivefold in 1 h and 20-fold by 3 h.
      By contrast, direct measurement of DNA damage by the terminal-deoxynucleotidyl
      transferase-mediated dUTP-biotin nick end-labeling assay shows no significant
      increase by 3 h and less than fourfold by 24 h. These findings indicate that PARS
      activity can provide a simple, sensitive, and early index of DNA damage following
      neurotoxic insults.

PMID- 7643122
TI  - Opposing actions of thrombin and protease nexin-1 on amyloid beta-peptide
      toxicity and on accumulation of peroxides and calcium in hippocampal neurons.
AB  - Amyloid beta-peptide (A beta) is the principal component of neuritic plaques in
      the brain in Alzheimer's disease (AD). Recent studies revealed that A beta can be
      neurotoxic by a mechanism involving free radical production and loss of cellular
      ion homeostasis, thus implicating A beta as a key factor in the pathogenesis of
      AD. However, other proteins are present in plaques in AD, including the protease
      thrombin and protease nexin-1 (PN1), a thrombin inhibitor. We therefore tested
      the hypothesis that thrombin and PN1 modify neuronal vulnerability to A beta
      toxicity. In dissociated rat hippocampal cell cultures the toxicity of A beta was
      significantly enhanced by coincubation with thrombin, whereas PN1 protected
      neurons against A beta toxicity. A beta induced an increase in levels of
      intracellular peroxides and calcium. Thrombin enhanced, and PN1 attenuated, the
      accumulation of peroxides and calcium induced by A beta. Taken together, these
      data demonstrate that thrombin and PN1 have opposing effects on neuronal
      vulnerability to A beta and suggest that thrombin and PN1 play roles in the
      pathogenesis of neuronal injury in AD.

PMID- 7643123
TI  - GM1 ganglioside in the nuclear membrane modulates nuclear calcium homeostasis
      during neurite outgrowth.
AB  - GM1 in the nuclear membrane, previously shown to be up-regulated during neurite
      outgrowth, has been found to influence nuclear Ca2+ flux during differentiation
      of Neuro-2a cells. Nuclei were isolated from cultured Neuro-2a cells before and
      after neuraminidase-induced neuritogenesis and incubated with 45Ca2+ for varying
      periods to determine uptake/efflux of Ca2+. At 5, 10, and 15 min 45Ca2+ levels in
      nuclei from differentiated cells were significantly lower than those in nuclei
      from untreated cells. The same result was obtained when the GM1 level was
      elevated artificially by preincubation of the nuclei in 10 microM GM1. In
      experiments designed to measure efflux specifically, isolated nuclei preincubated
      in GM1 released 45Ca2+ more rapidly than untreated nuclei. We conclude that one
      role of GM1 in the nuclear membrane is to alter Ca2+ regulatory mechanisms in the
      nucleus following onset of neuronal process outgrowth.

PMID- 7643124
TI  - Bovine chromaffin cells release a transforming growth factor-beta-like molecule
      contained within chromaffin granules.
AB  - Bovine chromaffin cells contain within their storage vesicles and release upon
      cholinergic stimulation a complex mixture of proteins and peptides. We present
      data suggesting that one of these proteins resembles transforming growth factor
      (TGF)-beta in terms of its biological activity. The assay used to assess the
      activity of TGF-beta is based on cells transfected with a plasminogen activator
      inhibitor-1 promoter-luciferase construct. The assay is highly specific in
      detecting TGF-beta 1, -beta 2, and -beta 3 but does not detect several cytokines
      and growth factors, such as fibroblast growth factor-2, transforming growth
      factor-alpha, platelet-derived growth factor-AB, insulin-like growth factor-1, or
      neurotrophin-3 or -4. Moreover, we show that this assay does not detect a wide
      range of TGF-beta superfamily members (activin A, bone morphogenetic protein-2, 
      4, -6, and -7, growth/differentiation factor-5, and glial cell line-derived
      neurotrophic factor). Chromaffin granules contain approximately 1 ng of TGF
      beta/10 mg of protein. The biological activity elicited by the chromaffin granule
      component can be neutralized by using an antibody against TGF-beta 1/beta 2/beta
      3. TGF-beta is releasable from cultured chromaffin cells stimulated with the
      cholinergic agonist carbachol (10(-5) M). These data suggest that TGF-beta is
      stored in chromaffin granules and can be released by exocytosis.

PMID- 7643125
TI  - Thyrotropin-releasing hormone.

PMID- 7643126
TI  - Identification of GABAA receptor subunits in rat retina: cloning of the rat GABAA
      receptor rho 2-subunit cDNA.
AB  - We identified GABAA receptor subunits in rat retina using PCR. The high degree of
      conservation among previously described members of ligand-gated anion channels in
      transmembrane domains was used to design degenerate sense and antisense
      oligonucleotides. These oligonucleotides were used as primers for PCR, which was
      applied to the rat retina cDNA. Analysis of clones derived from the PCR
      amplification identified the GABAA alpha 1, beta 1, beta 3, and gamma 2 subunits
      and the glycine alpha 1 subunit. In addition, two clones closely related to the
      human GABAA rho-subunit class were obtained. Molecular cloning revealed one of
      them as the rat counterpart of the human rho 2 subunit. Northern blot analysis
      demonstrated the expression of mRNAs for rho subunits in retina. These results
      further support the hypothesis that bicuculline-insensitive GABA channels in rat
      retina are comprised of rho subunits.

PMID- 7643127
TI  - Glutamate receptor activation regulates mRNA at both transcriptional and
      posttranscriptional levels.
AB  - Previous studies from this laboratory have demonstrated that extracellular
      calcium entry through the NMDA subtype of glutamate receptors in hippocampal
      neurons selectively down-regulated ligatin gene expression in a rapid and long
      lasting manner. Here we investigated the molecular mechanism that underlies this
      phenomenon. We demonstrate that glutamate receptor activation transiently
      increased the transcriptional activity of the ligatin gene and simultaneously
      shortened the half-life of its message. Using nuclear run-on assays and northern
      analyses of total RNA from alpha-amanitin-treated cells, we measured the effects
      of glutamate on the transcriptional activity and mRNA stability of the ligatin
      gene. The transcriptional activity of ligatin was found to be transiently
      increased (1.4-fold) 20 min after the addition of glutamate, with a return to
      basal levels by 60 min. Thus, the glutamate-dependent decrease in ligatin message
      could not be explained by a decline in its synthesis. Instead, concurrent with
      transcriptional up-regulation, glutamate shortened the half-life of the ligatin
      message from 10 h to 58 min, leading to a net decrease (0.7-fold) in its steady
      state levels by 60 min. This posttranscriptional destablization of ligatin mRNA
      was mimicked by the translation inhibitor, cycloheximide, but not by puromycin.
      This finding indicated that the stability of ligatin mRNA was translation
      independent and distinguished this posttranscriptional regulatory mechanism from
      those previously described. Moreover, using in situ hybridization and confocal
      microscopy, we showed that control of message stability occurred both in the cell
      body and in the dendritic regions distant from the nucleus.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7643128
TI  - Pituitary adenylate cyclase-activating polypeptide (PACAP) regulation of
      sympathetic neuron neuropeptide Y and catecholamine expression.
AB  - Two forms of pituitary adenylate cyclase-activating polypeptide (PACAP), the 38-
      and 27-amino-acid forms (PACAP38 and PACAP27, respectively), which share amino
      acid sequence homology with vasoactive intestinal peptide (VIP), were evaluated
      for their abilities to regulate sympathetic neuron catecholamine and neuropeptide
      Y (NPY) expression. PACAP38 and PACAP27 potently and efficaciously stimulated NPY
      and catecholamine secretion in primary cultured superior cervical ganglion (SCG)
      neurons; 100- to 1,000-fold higher concentrations of VIP were required to
      modulate secretion, suggesting that SCG neurons express the PACAP-selective type
      I receptor. PACAP38 elicited a sustained seven- to ninefold increase in the rate
      of NPY secretion and threefold stimulation in the rate of catecholamine release.
      PACAP38 and PACAP27 produced parallel neuronal NPY and catecholamine release, but
      cellular levels of NPY and catecholamines were differentially regulated.
      Sympathetic neuron NPY content was decreased, whereas cellular total
      catecholamine levels were elevated by the PACAP peptides; total NPY and
      catecholamine levels (secreted plus cellular content) were increased. In concert
      with the increased total peptide and transmitter production, pro-NPY and tyrosine
      hydroxylase mRNA levels were elevated. Furthermore, PACAP38 was more efficacious
      than PACAP27 in regulating pro-NPY and tyrosine hydroxylase mRNA. SCG neuronal
      expression of mRNA encoding the type I PACAP receptor further supported the
      studies demonstrating that sympathetic neuronal levels of NPY and catecholamine
      content and secretion and mRNA are differentially regulated by the PACAP
      peptides.

PMID- 7643129
TI  - Regulation of phenylethanolamine N-methyltransferase gene expression by
      imidazoline receptors in adrenal chromaffin cells.
AB  - As adrenal medullary chromaffin cells express imidazoline binding sites in the
      absence of alpha 2-adrenergic receptors, these cells provide an ideal system in
      which to determine whether imidazolines can influence catecholamine gene
      expression through nonadrenergic receptors. This study evaluates the ability of
      clonidine and related drugs to regulate expression of the gene for the
      epinephrine-synthesizing enzyme phenylethanolamine N-methyltransferase (PNMT) in
      the rat adrenal gland and in bovine adrenal chromaffin cell cultures. In vivo,
      PNMT and tyrosine hydroxylase (TH) mRNA levels increase in rat adrenal medulla
      after a single injection of clonidine. Clonidine also dose-dependently stimulates
      PNMT mRNA expression in vitro in primary cultures of bovine chromaffin cells,
      with a threshold dose of 0.1 microM. Other putative imidazoline receptor
      agonists, including cimetidine, rilmenidine, and imidazole-4-acetic acid,
      likewise enhance PNMT mRNA production showing relative potencies that correlate
      with their binding affinities at chromaffin cell I1-imidazoline binding sites.
      The effects of clonidine on PNMT mRNA appear to be distinct from and additive
      with those exerted by nicotine. Moreover, neither nicotinic antagonists nor
      calcium channel blockers, which attenuate nicotine's influence on PNMT mRNA
      production, diminish clonidine's effects on PNMT mRNA. Although 100 microM
      clonidine diminishes nicotine-stimulated release of epinephrine and
      norepinephrine in chromaffin cells, this effect appears unrelated to stimulation
      of imidazoline receptor subtypes. This is the first report to link imidazoline
      receptors to neurotransmitter gene expression.

PMID- 7643130
TI  - Differential stimulation of somatostatin but not neuropeptide Y gene expression
      by quinolinic acid in cultured cortical neurons.
AB  - Somatostatin (SS) and neuropeptide Y (NPY) are coproduced in a subpopulation of
      neurons that are selectively resistant to NMDA neurotoxicity. We have previously
      reported that quinolinic acid (QUIN), an NMDA receptor agonist, augments SS mRNA
      in cultured fetal rat cortical neurons. This study examines coregulation of SS
      and NPY by QUIN and NMDA in cultured cortical neurons and compares the effects of
      these agents with those of forskolin and phorbol 12-myristate 13-acetate (PMA),
      known to activate SS and NPY gene transcription by protein kinase A- and protein
      kinase C-dependent mechanisms. In addition, transcriptional regulation of the SS
      gene was investigated by acute transfection of cortical cultures with an SS
      promoter-chloramphenicol acetyltransferase (CAT) construct. QUIN and NMDA
      displayed dose-dependent fourfold augmentation of levels of mRNA for SS but not
      for NPY. In contrast, forskolin and PMA increased both SS and NPY mRNA levels.
      QUIN- and NMDA-mediated induction of SS mRNA was blocked by the NMDA receptor
      antagonist (-)-2-amino-5-phosphonovaleric acid and displayed regional brain
      specificity because it was not observed in fetal hypothalamic cell cultures. In
      time course studies, the effects of QUIN/NMDA on SS mRNA occurred after a latency
      of 8 h, indicating a delayed effect. Cortical cells transfected with pSS-750 CAT
      showed three- to fourfold stimulation of CAT activity with forskolin but not by
      QUIN or NMDA. These data reveal a dose-dependent, tissue-specific, NMDA receptor
      mediated stimulation of SS but not NPY mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7643131
TI  - Sympathoadrenal progenitors in embryonic chick sympathetic ganglia show distinct
      responses to glucocorticoid hormones.
AB  - The sympathoadrenal cell lineage originates from the neural crest and comprises
      the neurons of sympathetic ganglia, adrenal and extra-adrenal chromaffin cells,
      and the so-called small intensely fluorescent cells. In vitro studies using
      mammalian immature chromaffin cells, adrenal or sympathetic ganglionic
      progenitors, or ganglionic small intensely fluorescent cells, have suggested that
      glucocorticoid hormones are essential for inhibiting neuronal differentiation of
      sympathoadrenal progenitors and promoting the chromaffin cell phenotype. In avian
      systems, however, the distinct cellular phenotypes in this lineage and the
      molecular cues underlying their differentiation have not been fully explored. In
      the chick embryo, early sympathetic ganglion anlagen are populated by granule
      containing cells that morphologically resemble small intensely fluorescent cells
      and chromaffin cell progenitors. These cells subsequently disappear from the
      ganglia, by death and by transition into fully differentiated sympathetic
      neurons, as indicated by the appearance of cells that are ultrastructurally
      intermediate between granule-containing cells and fully differentiated neurons
      (granule-containing cells in transition). In the present study, we show that
      treatment of cultured sympathetic cells dissociated from embryonic day (E) 7, 9,
      or 11 lumbar sympathetic ganglia with the glucocorticoid hormones hydrocortisone
      or corticosterone has neither an inhibitory nor an inductive effect on phenotypes
      of granule-containing cells or granule-containing cells in transition. In cell
      cultures of E15 ganglia, however, glucocorticoid treatment induces a granule
      containing cell resembling the granule-containing phenotype. These results
      suggest that the early granule-containing cells and granule-containing cells in
      transition in chick sympathetic ganglia are not the counterparts of
      glucocorticoid-responsive mammalian small intensely fluorescent or chromaffin
      progenitor cells, despite their morphological similarity. However, E15
      sympathetic ganglia apparently contain a glucocorticoid-responsive progenitor
      population that can differentiate into chromaffin-like cells. These progenitors
      seem to require a systemic or intraganglionic developmental signal or undergo a
      temporal switch that renders them susceptible to glucocorticoids.

PMID- 7643132
TI  - Localization of dopamine D2 receptor mRNA in glomus cells of the rabbit carotid
      body by in situ hybridization.
AB  - The localization of mRNA coding for the dopamine D2 receptor was studied in the
      rabbit carotid body using in situ hybridization with synthetic 35S-labelled
      oligodeoxynucleotides. Using autoradiography on cryostat or semi-thin sections,
      labelling was observed over the cytoplasm of glomus cells, but not over
      sustentacular cells. A quantitative study showed that labelling intensity (silver
      grain density) was increased by haloperidol treatment. These results suggest that
      glomus cells express the dopamine D2 receptor gene and that this expression is
      regulated.

PMID- 7643133
TI  - Localization of NADPH-diaphorase activity in the submucous plexus of the guinea
      pig intestine: light and electron microscopic studies.
AB  - The localization of reduced nicotinamide adenine dinucleotide phosphate
      diaphorase in the submucous plexus of duodenum, jejunum, ileum, proximal colon,
      distal colon and rectum in the guinea-pig was examined histochemically by light
      and electron microscopy. The majority of reactive submucous neurons displayed
      features common to either Dogiel type I or type II neurons; some were closely
      adherent to the outer walls of lymphatic vessels. The use of 2-(2'
      benzothiazolyl)-5-styryl-3-(4'-phthalhydrazidyl) tetrazolium chloride (BSPT) at
      the ultrastructural level showed that nicotinamide adenine dinucleotide phosphate
      diaphorase is a membrane-associated protein widely distributed in the cells,
      including the rough endoplasmic reticulum, Golgi apparatus and synaptic vesicles
      in the axon terminals associated with submucous neurons. On the basis of their
      diaphorase reactivity or the lack of it, the submucous neuronal somata and their
      associated terminals were observed to form several different kinds of synaptic
      configurations. The present quantitative analysis showed that the frequency of
      reactive submucous neurons in the large intestine was significantly higher than
      in the small intestine. Based on the ultrastructural localization of the
      diaphorase reaction product in positive cells, it is speculated that nitric oxide
      might be synthesized within the neurons. The demonstration of different synaptic
      configurations in the submucous ganglia suggests that the functional interaction
      between submucous neurons is extremely complex. Finally, the higher frequency of
      diaphorase reactive submucous neurons in the large intestine than in the small
      intestine indicates that submucous neurons in these two gut regions may not play
      equivalent roles.

PMID- 7643134
TI  - Synaptogenesis and distribution of presynaptic axonal varicosities in low density
      primary cultures of neocortex: an immunocytochemical study utilizing synaptic
      vesicle-specific antibodies, and an electrophysiological examination utilizing
      whole cell recording.
AB  - Low-density primary cultures of neocortical neurons were utilized to examine: (i)
      early interactions of growing neurites with morphological characteristics of
      axons with other neuronal elements, and (ii) the distribution of presynaptic
      axonal varicosities closely apposed to MAP-2 immunoreactive, putatively
      postsynaptic, dendrites. At the light microscopical level axonal varicosities,
      presumably presynaptic terminals, were identified using immunocytochemistry
      incorporating antibodies specific for the synaptic vesicle antigens synaptophysin
      and synapsin. The presence of synaptophysin- and synapsin-immunoreactive
      swellings along axonal processes was first detected at 5 days post-plating and
      was also apparent in axons growing in isolation. At 5-7 days in vitro,
      immunolabelled axonal varicosities in close apposition to putative postsynaptic
      dendrites (MAP-2 immunoreactive) dendrites were detected. Electrophysiologically
      active synaptic contacts can also readily be detected at this stage. After 3
      weeks in vitro presynaptic contacts do appear to be distributed heterogeneously
      along postsynaptic dendrites of many neurons in culture. As the culture matures a
      higher number of presynaptic profiles can be seen along dendrites, with a
      centrifugal distribution, e.g. a higher density of presynaptic axonal terminals
      in close apposition to more distal regions of larger dendrites, putatively
      considered to be apical dendrites of pyramidal-like neurons. In our cultures, the
      overall increase in the density and the pattern of distribution of presynaptic
      axon terminals immunoreactive for synaptic vesicle antigens closely apposed to
      putative post-synaptic structures mimics the general postnatal increase of
      synaptic density in the neocortex in vivo. Thus, low density primary cultures of
      neocortical neurons offer a valuable system to explore and manipulate (i) the
      molecular and cellular basis of neocortical synaptogenesis, and (ii) the
      pharmacology of neocortical synaptic transmission.

PMID- 7643135
TI  - Cellular and molecular reactions in mouse muscles after myoblast implantation.
AB  - Implantation of skeletal muscle precursor cells is a potential means of cell
      mediated gene therapy. One unresolved question is the degree of immunogenicity of
      such myoblasts. We designed the extreme situation of implanting cells of a non
      histocompatible myoblast cell line into cryodamaged, but regeneration-capable,
      muscles of adult mice. Without immunosuppression donor cells are rejected within
      the first weeks. Immunosuppression with Cyclosporin A prevented invasion of T
      lymphocytes and allowed differentiation of implanted myoblasts into myofibres as
      well as down-regulation of MHC expression. Still, withdrawal of Cyclosporin A
      after 4 weeks triggered lymphocyte invasion and cytotoxic cell reactions with
      rejection of donor tissue. Although the vast majority of muscle fibres was MHC
      negative 1-4 days after Cyclosporin A withdrawal, single small desmin-positive
      profiles were weakly positive for donor MHC. Parallel with the increase in the
      number of lymphocytes, larger numbers of small and large muscle fibres expressed
      high levels of either donor, host or both, class I--but not class II--molecules.
      Surprisingly, immune reactions continued over several months, causing gradual
      loss of muscle tissue. Donor class I molecules persisted for more than 6 months
      after Cyclosporin A withdrawal, clearly indicating survival of donor muscle
      fibres despite ongoing rejection. Indirect evidence on the other hand suggests
      additional loss of host fibres, possibly caused by cytokine release from the
      immune cells (bystander damage). We conclude that transient treatment with
      Cyclosporin A induced a kind of tolerance related to the maturation and down
      regulation of class I antigens in donor muscle fibres. It is suggested that the
      start of immune reaction following Cyclosporin A withdrawal is initiated by
      remaining small amounts of donor MHC molecules, possibly related to the
      continuous proliferation of the cell-lined-derived donor myoblasts.

PMID- 7643136
TI  - Persistent pure verbal amnesia and transient aphasia after left thalamic
      infarction.
AB  - A 57-year-old right-handed man suffered persistent pure verbal amnesia (PPVA) and
      transient aphasia after left thalamic infarction. A neuroanatomical study with
      magnetic resonance imaging to identify the site of the lesion showed destruction
      of the internal medullary lamina (IML), mammillothalamic tract (MTT), the
      ventrolateral nucleus (VL) and the lower one-third of the medial nucleus. As
      regions critical for PPVA are unknown, we reviewed the cases of PPVA after left
      thalamic infarction reported in the literature. These suggest that confined
      destruction of the IML, MTT and VL in the left thalamus can produce PPVA.

PMID- 7643137
TI  - Molecular diagnosis of hereditary neuropathy with liability to pressure palsies
      (HNPP) by detection of 17p11.2 deletion in Italian patients.
AB  - Hereditary neuropathy with a liability to pressure palsies (HNPP) is an autosomal
      dominant disorder characterized by recurrent pressure palsies generally
      precipitated by minor trauma; weakness and paraesthesia usually improve and
      recover completely in a few months. By Southern blotting and fluorescent in situ
      hybridization analysis we confirm the presence of a 17p11.2 deletion in familial
      and in isolated cases of HNPP, suggesting that molecular analysis of the 17p11.2
      region could also be a reliable and non-invasive method of diagnosis in sporadic
      cases, where a correct diagnosis usually requires a nerve biopsy. Although HNPP
      is a mild disease and not all patients seek medical attention, a presymptomatic
      diagnosis is useful for assessing the risk during genetic counselling, due to the
      inheritance of the mutation.

PMID- 7643138
TI  - Type 3 GM1 gangliosidosis: clinical and neuroradiological findings in an 11-year
      old girl.
AB  - An 11-year-old Japanese girl was diagnosed as having type 3 GM1 gangliosidosis by
      clinical symptoms and enzyme assay. She was the youngest among the patients with
      type 3 GM1 gangliosidosis whose clinical and neuroradiological findings have been
      documented. Clumsiness since early infancy and dystonia since early childhood
      which progressed slowly without mental deterioration and dysmorphism led us to
      the diagnosis of type 3 GM1 gangliosidosis. Genotype determination showed point
      mutation in exon 2 of the beta-galactosidase gene, which is common among the
      patients reported in Japan. T2-weighted MRI demonstrated bilateral symmetrical
      hypointensity in the putamen and globus pallidus. Single photon emission computed
      tomography using 99mTc-HMPAO showed bilateral hyperperfusion in the basal ganglia
      which decreased gradually during 1 year of observation. Twenty-two patients with
      type 3 GM1 gangliosidosis reported in the literature whose onset was at under 15
      years of age were reviewed.

PMID- 7643140
TI  - Changes of circadian blood pressure patterns and cardiovascular parameters
      indicate lateralization of sympathetic activation following hemispheric brain
      infarction.
AB  - The effects of left- and right-sided hemispheric brain infarction on variability
      in circadian blood pressure and cardiovascular measures were investigated in 35
      patients to test for asymmetry of the sympathetic consequences of stroke. No
      significant differences regarding age, size of infarction or extent and frequency
      of damage to the insular cortex could be detected between the two groups.
      Patients with right-sided infarction showed a significantly reduced circadian
      blood pressure variability [diastolic: -1% (95% CI -4 to 1) vs -6% (-9 to -2); P
      < 0.05] and a higher frequency of nocturnal blood pressure increase (47% vs 35%;
      P < 0.05) as compared with patients with left-sided infarction. Right-sided
      infarction was also associated with higher serum noradrenaline concentrations
      [546 pg/ml (95% CI 415-677) vs 405 pg/ml (266-544); P < 0.05], and ECG more
      frequently showed QT prolongation (53% vs 35%; P < 0.05) and cardiac arrhythmias
      (67% vs 20%; P < 0.005). However, irrespective of the hemisphere damaged,
      patients with insular infarction showed the most pronounced changes of these
      parameters. In addition, two patients with right-sided strokes (13%) involving
      the insula, but none with a left-sided infarction, developed myocardial
      infarction. These findings suggest lateralization of sympathetic activation with
      right-sided dominance for sympathetic effects following hemispheric stroke.

PMID- 7643139
TI  - Genotype to phenotype correlations in mitochondrial encephalomyopathies
      associated with the A3243G mutation of mitochondrial DNA.
AB  - We studied 22 subjects carrying the A3243G point mutation of human mitochondrial
      DNA (mtDNA). In 14 cases the clinical phenotype was characterized by
      mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes
      (MELAS), while 8 patients had chronic progressive external ophthalmoplegia
      (CPEO). The proportion of A3243G heteroplasmy in muscle was determined by two
      methods; densitometry on a diagnostic restriction-fragment length polymorphism
      and solid-phase mini-sequencing. We found a highly significant inverse
      correlation between the percentage of A3243G mutation and the specific activity
      of complex I, the respiratory complex with the highest number of mtDNA-encoded
      subunits, suggesting a direct effect of the mutation on mtDNA translation. No
      correlation was observed between the percentage of mutated mtDNA and the presence
      or absence of specific clinical features, such as stroke, ophthalmoplegia and
      diabetes mellitus. However, in the MELAS group the percentage of mutated mtDNA
      molecules was strongly correlated with the age of onset, while no such
      correlation was found in the CPEO group, suggesting a different time-dependent
      evolution of the mutation in the two groups. Finally, in contrast with other
      mtDNA mutations associated with ragged-red fibres (RRF), in both MELAS3243 and
      CPEO3243 we observed a high proportion of RRF that were positive to the
      histochemical reaction to cytochrome c oxidase, a morphological feature that
      seems to be specific for the neuromuscular phenotypes associated with mutations
      affecting the tRNA(Leu(UUR)) gene.

PMID- 7643141
TI  - Intrathecal immune response in patients with neuroborreliosis: specificity of
      antibodies for neuronal proteins.
AB  - Cerebrospinal fluid (CSF) and serum samples of 47 patients with serologically
      proven neuroborreliosis were examined by Western blotting for antibodies to a
      crude extract of human cortex (CNS) comprising a multitude (> 40) of protein
      bands. Intrathecal synthesis of total immunoglobulins was determined by the
      Reiber formula and of autoantibodies to CNS proteins by enzyme-linked immunoassay
      (ELISA) and by Western blotting. Employing ELISA, intrathecal synthesis of
      autoantibodies (IgG, IgM and/or IgA) was demonstrated in 40 of 47 patients with
      neuroborreliosis (85%), in 5 of 40 with multiple sclerosis (12%), and in 22 of 40
      with viral meningoencephalitis (55%). Of 40, 35 and 15 patients with
      neuroborreliosis and an intrathecal synthesis of total IgG, IgM or IgA, 20
      revealed an intrathecal production of IgG antibodies (50%), 24 of IgM antibodies
      (68%) and 6 of IgA autoantiodies (40%) in the CSF. The specificity of
      autoantibodies differed greatly between most patients. Of 24 different CNS
      proteins which elicited an immune response in various patients, identities could
      be determined only for the myelin basic protein (5 of 40) and for the three
      neurofilament proteins (NF-68, NF-150, NF-200) (13 of 40 patients). In this
      limited number of patients no significant correlation between individual clinical
      symptoms and certain autoantiodies could be detected. The higher frequency of
      intrathecally produced autoantibodies in patients with neuroborreliosis is
      assumed to result from mitogenic rather than specific activation of autoreactive
      B-cell clones by Borrelia burgdorferi. The pathogenic relevance of these
      autoantibodies remains to be determined.

PMID- 7643142
TI  - Lupus transverse myelopathy: better outcome with early recognition and aggressive
      high-dose intravenous corticosteroid pulse treatment.
AB  - Seven patients with transverse myelopathy (TM) were found to have systemic lupus
      erythematosus (SLE). Four patients had no prior diagnosis of SLE. All patients
      had positive antinuclear antibody (ANA). All patients had a spinal syndrome which
      progressed to TM with cervical or thoracic levels. The diagnosis of TM was
      confirmed with neurological tests and neuro-radiographic studies. Delay in
      diagnosis and treatment resulted in a poor outcome. Four patients died and one
      remained wheelchair-bound. Only two patients who received high-dose IV pulse
      steroid within 1 week of onset of TM had a good outcome, with full ability to
      ambulate without assistance. Our experience suggests that early diagnosis with
      early treatment using high-dose IV steroid affects the mortality and improves the
      outcome.

PMID- 7643143
TI  - Sequence of the human homologue of a mitochondrially encoded murine
      transplantation antigen in patients with multiple sclerosis.
AB  - There is some evidence that mitochondrial genes may contribute to susceptibility
      to multiple sclerosis (MS), and a mitochondrial DNA-encoded peptide, the N
      terminal portion of NADH-dehydrogenase subunit 1, acts as a transplantation
      antigen in mice. We have analysed the DNA sequence of the corresponding region of
      human mitochondrial DNA in 87 patients with MS, 10 with Leber's hereditary optic
      neuropathy in association with an MS-like illness, and 31 control subjects. This
      sequence appears to be highly conserved. Only three base pair changes were
      identified, each being found once only in one control and two patients, and these
      are likely to be harmless polymorphisms. There is thus no evidence that
      polymorphism in this region contributes to genetic susceptibility in MS.

PMID- 7643144
TI  - Rare diseases mimicking acute vertebrobasilar artery thrombosis.
AB  - Acute ischaemia of the vertebrobasilar circulation leads to a variety of clinical
      manifestation and is mostly due to cardiogenic or artery-to-artery embolism. We
      describe four neurological emergency situations involving vertebrobasilar artery
      aclusion of other origins; basilar migraine, extrinsic compression by rheumatoid
      inflammatory tissue, generalized vasculitis in subacute rheumatic fever and
      basilar artery dissection. The differential diagnosis of acute vertebrobasilar
      artery occlusion may have an important impact on patient management.

PMID- 7643145
TI  - Paroxysmal dysarthria and ataxia in a patient with Behcet's disease.
AB  - The paroxysmal attacks which are frequently encountered in the course of multiple
      sclerosis (MS) are characterised by their sudden onset, short duration and
      frequent repetition. Such attacks have also been reported in some other diseases
      affecting the CNS, such as systemic lupus erythematosus. However, to our
      knowledge, they have not been reported in neuro-Behcet's disease (NBD). A patient
      with NBD who developed paroxysmal dysarthriaataxia attacks is presented, and the
      similarity of some clinical, laboratory, and neuroradiological aspects of NBD and
      MS are discussed with special emphasis on magnetic resonance imaging findings.

PMID- 7643146
TI  - Severe cerebellar atrophy in the panencephalopathic type of Creutzfeldt-Jakob
      disease: a case report.

PMID- 7643147
TI  - Carotid pseudo-valvular fold: a probable cause of ischaemic stroke.

PMID- 7643148
TI  - Diagnosis and management of spinal metastases from breast cancer.

PMID- 7643150
TI  - Surgery for metastatic spinal disease.
AB  - Cancer is a leading cause of death in the United States. Despite the development
      of advanced treatment for many malignancies, a large number of patients will
      require evaluation and possible surgical intervention for lesions which have
      metastasized to or directly invaded the spinal column. The recommendations for
      operative intervention on these patients should be made following evaluations by
      multiple specialties, both medical and surgical. An improved understanding of the
      pathophysiology of malignancy and the development of advanced adjunctive
      treatment modalities have improved the quality and duration of life in many
      patients. Recent studies have demonstrated the utility of early surgery when
      combined with other treatment modalities. Surgical techniques for tumor resection
      and spine stabilization have improved the outcome of patients reported in
      multiple surgical series. A multidisciplinary approach to treatment of cancer
      patients with spinal involvement affords the patient an optimal outcome.

PMID- 7643149
TI  - The use of radiation in the management of spinal metastases.

PMID- 7643151
TI  - Nonclock behavior of inferior olive neurons: interspike interval of Purkinje cell
      complex spike discharge in the awake behaving monkey is random.
AB  - 1. Complex spikes of cerebellar Purkinje cells recorded from awake, behaving
      monkeys were studied to determine the extent to which their discharge could be
      quantified as periodic. Three Rhesus monkeys were trained to perform up to five
      different tasks involving rotation of the wrist in relation to a visual cue.
      Complex spike activity was recorded during task performance and intertrial time.
      Interspike intervals were determined from the discharge of each of 89 Purkinje
      cells located throughout lobules IV, V, and VI. Autocorrelation and Fourier
      transform of the autocorrelation function were performed on the data. In
      addition, the activity from one cell was transformed so that the discharge
      occurred on the beat of a 10-Hz clock, and in a further transformation, on the
      beat of a noisy 10-Hz clock. These transformed data were then analyzed as
      described above. 2. Fourier transform of the autocorrelogram function of the data
      that had been transformed to a 10-Hz clock, and that of the noisy 10-Hz clock,
      both showed a prominent peak at 10 Hz. However, the autocorrelograms and the
      Fourier transforms of the autocorrelogram functions failed to reveal a prominent
      periodicity for the actual discharge of any of cells, at any frequency up to 100
      Hz: the discharge appeared random with respect to the interspike interval. The
      discharge was not random with respect to behavior. Complex spike activity was
      commonly time locked to the start of wrist movement. We examined this discharge
      to see whether oscillatory discharge could be seen after alignment of the data on
      the start of wrist movement, or after alignment of the data on the complex spike
      occurring peri-start of wrist movement. No oscillation was seen for either
      alignment. 3. The inferior olive, which sends its climbing fibers to the
      cerebellum, has been implicated in such different activities as 1) pathological
      tremor of the soft palate, 2) physiological tremor, 3) the normal initiation of
      all bodily movement, and 4) motor learning. Previous work in pharmacologically or
      surgically treated animals has shown that, under some conditions, the discharge
      of these neurons is periodic and synchronous. This firing pattern has been
      interpreted to support a role in the first two activities. But measurements
      reported here in the awake monkey show just the opposite: the discharge is
      aperiodic to the extent of being random. As such, the inferior olive cannot be a
      "motor clock" in the general role that has been proposed.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 7643152
TI  - Responses of monkey inferior temporal neurons to luminance-, motion-, and texture
      defined gratings.
AB  - 1. We recorded from neurons responsive to gratings in the inferior temporal (IT)
      cortices of macaque monkeys. One of the monkeys performed an orientation
      discrimination task; the other maintained fixation during stimulus presentation.
      Stimuli consisted of gratings based on discontinuities in luminance, relative
      motion, and texture. 2. IT cells responded well to gratings defined solely by
      relative motion, implying either direct or indirect motion input into IT, an area
      that is part of the ventral visual cortical pathway. 3. Response strength in
      general did not depend on the cue used to define the gratings. Latency values
      observed for the two static grating types (luminance- and texture-defined
      gratings) were similar, but significantly shorter than those measured for the
      kinetic gratings. 4. Stimulus orientation had a significant effect in 27%, 27%,
      and 9% of the cells tested with luminance-, kinetic-, and texture-defined
      gratings, respectively. 5. Only a small proportion of cells were orientation
      sensitive for more than one defining cue. The average preferred orientation for
      luminance and kinetic gratings matched; the tuning width was similar for the two
      cues. 6. Our results indicate that IT cells may contribute to cue-invariant
      coding of boundaries and edges. We discuss the relevance of these results to
      visual perception.

PMID- 7643153
TI  - Emergence of complex receptive field properties of ganglion cells in the
      developing turtle retina.
AB  - 1. Receptive field properties of adult retinal ganglion cells are well
      documented, but little is known about their development. We made extracellular
      recordings of activity from turtle retinal ganglion cells during embryogenesis
      (stages 22-26), during the first 40 days posthatching, and in adults. 2. From
      stage 22 the cells fired in spontaneous recurring bursts, and from stage 23 they
      responded to light. Polar plots of the responses to motion were highly
      anisotropic in early embryonic cells. More than 40% of embryonic cells exhibited
      multiaxis anisotropy, and only 6% were statistically isotropic. The incidence of
      anisotropic cells gradually decreased throughout development. The incidence of
      isotropic cells and the excitatory receptive field diameters of all ganglion
      cells gradually increased during development and their maturation coincided with
      the disappearance of the spontaneous bursts (2-4 wk posthatching). 3. Both
      sensitivities to stimulus orientation and direction of motion were observed at
      the earliest stages of development. However, orientation selectivity reached a
      peak incidence at hatching, whereas directional selectivity completely
      disappeared, only to reappear in adults. 4. These results show that mature
      spatiotemporal receptive field properties of retinal ganglion cells emerge from
      initially highly anisotropic properties, which may reflect an immature, polarized
      dendritic layout. Their maturation might be mediated by dendritic outgrowth and
      strengthening of excitatory synaptic connections, which could be induced by
      spontaneous activity and driven to maturation by exposure to light at birth.
      Mature directional selectivity seems to require visual experience or the late
      establishment of a specialized inhibitory synaptic drive.

PMID- 7643154
TI  - Dynamics of abducens nucleus neurons in the awake rabbit.
AB  - 1. We recorded abducens neurons, identified by electrical stimulation as
      internuclear neurons or motoneurons, in awake rabbits. The relationship of firing
      rate to eye movement was determined from responses during stable fixations,
      sinusoidal rotation in the light (0.05-0.8 Hz), and triangular optokinetic
      stimulation at 0.1 Hz. 2. All abducens neurons were excited during temporal
      movement of the ipsilateral eye. Temporal and nasal saccades were associated with
      bursts or pauses, respectively, in the firing rate. 3. Motoneurons and
      internuclear neurons are qualitatively indistinguishable. There was no
      significant quantitative difference between the phase and sensitivity of the two
      groups for 0.2-Hz sinusoidal rotation in the light. 4. On the basis of the
      response to stable eye positions, we determined static eye position sensitivity
      of the abducens neuron pool to be 8.2 +/- 2.5 (SD) spikes.s-1/0, with a static
      hysteresis of 8.9 spikes/s (1.14 +/- 0.37 degrees). 5. We determined apparent eye
      position sensitivity (k) and apparent eye velocity sensitivity (r) from the
      responses to sinusoidal rotation in the light. k increases and r decreases with
      stimulus frequency, which indicates that the simplest transfer function mediating
      conversion of abducens nucleus (VI) firing rate to eye position (E) has two poles
      and one zero. 6. The VI-->E relationship has an "amplitude nonlinearity,"
      manifest as a tendency for k, r, and firing rate phase lead to decrease as eye
      movement amplitude increases at a fixed frequency. On a percentage basis, phase
      is less affected than are the sensitivities. The nonlinearity becomes less
      pronounced for stimulus amplitudes > 2.5 degrees, and consequently a linear model
      of the VI-->E transformation remains useful, provided that consideration is
      restricted to the appropriate range of stimulus/response amplitudes. 7. We
      determined time constants of the linear two-pole, one-zero transfer function from
      the variation of r/k versus stimulus frequency. The pole time constants were T1 =
      3.4 s and T2 = 0.28 s, and the zero time constant (Tz) = 1.6 s. The magnitude of
      Tz was corroborated by measuring the time constant of the exponential decay in
      firing rate after step changes in eye position. This transient method yielded a
      Tz of 1.1 s. 8. The time constants of the VI-->E transfer function are roughly 10
      times larger than those reported for the rhesus macaque. The difference is
      attributable to the reported 10-fold lower stiffness of the rabbit oculomotor
      plant, which may in turn relate to rabbits postulated lower degree of activation
      of extraocular muscles at any given position.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7643155
TI  - Dynamics of rabbit vestibular nucleus neurons and the influence of the flocculus.
AB  - 1. We recorded single vestibular nucleus neurons shown by electrical stimulation
      to receive floccular inhibition [flocculus receiving neurons (FRNs)] and/or to
      project toward midbrain motoneuronal pools [midbrain projecting neurons (MPNs)]
      in awake, head-fixed rabbits during compensatory eye movements. Stimuli included
      head rotation in the light, head rotation in the dark, and rotation of an
      optokinetic drum about the animal. We employed sinusoidal and triangular position
      profiles in the 0.05- to 0.8-Hz frequency band. We also examined transient
      responses to step changes in eye position. 2. We found identified vestibular
      nucleus cells (i.e., FRN/non-MPNs, FRN/MPNs, and non-FRN/MPNs) in the
      parvocellular and magnocellular portions of the medial vestibular nucleus, at the
      rostrocaudal level of the dorsal acoustic stria. 3. All identified vestibular
      nucleus neurons were excited during ipsilateral (relative to side of recording)
      head rotation and contralateral eye rotation. 4. The neuronal firing rates could
      be related to eye position and its time derivatives, and that relationship could
      be approximated by a two-pole, one-zero linear transfer function. As with
      abducens neurons, a more detailed approximation requires inclusion of two
      nonlinearities-a hysteresis and a variable sensitivity term that increases as eye
      movement amplitude decreases. 5. When the vestibuloocular reflex is suppressed by
      a conflicting full-field visual stimulus [visual vestibular conflict condition
      (VVC)], vestibular nucleus neuron modulation is largely suppressed. The remaining
      modulation is motoric in nature, because it can be related to the residual eye
      movements. Cells with "sensory vestibular signals," i.e., cells whose modulation
      during VVC correlates better with head rotation than eye movement, were not
      encountered. 6. We examined the dependence of firing rate parameters on stimulus
      modality. All neurons exhibited increased phase lead with respect to abducens
      nucleus neurons during stimuli involving head rotation. This finding could
      indicate that vestibular-derived inputs are inhomogeneously distributed on
      premotor neurons and that the studied premotor population receives a stronger
      vestibular input than another premotor group, not recorded in the current
      experiments. 7. FRNs and non-FRNs were similar in their qualitative response to
      the fast phases, the applicability of the two-pole, one-zero transfer function,
      hysteresis, and the amplitude nonlinearity. 8. FRNs differed from non-FRNs in
      having a phase advanced firing rate at all stimulus frequencies during visual and
      vestibular stimuli. The phase difference suggests that one role of the rabbit
      flocculus is to regulate phase of the net premotor signal.

PMID- 7643156
TI  - Direction biases of X and Y type retinal ganglion cells in the cat.
AB  - 1. It has been reported that in the cat only a specialized group of retinal
      ganglion cells constituting approximately 1% of the overall population are
      direction sensitive. Two major groups of retinal ganglion cells, the X and Y
      cells, have been reported not to be sensitive to the direction of stimulus
      motion. 2. We recorded action potentials of retinal ganglion cells intraocularly.
      We studied quantitatively the visual responses elicited by drifting sinusoidal
      gratings of various spatial frequencies, bars, and spots. 3. The results confirm
      previous reports that most cat retinal ganglion cells exhibit orientation biases
      when tested with gratings of relatively high spatial frequency. 4. Additionally,
      we find that 22% of X and 34% of Y type retinal ganglion cells exhibit direction
      biases. Overall, Y cells displayed significantly stronger direction biases than
      did X cells. 5. In general, direction biases are clearest when the test gratings
      are of relatively low spatial frequency. 6. The direction biases of X and Y cells
      subserving the central 15 degrees of retina were weaker than those of cells
      subserving more peripheral regions. 7. The direction-biased responses of cat
      ganglion cells were similar to those of X and Y type relay cells in the cat
      dorsal lateral geniculate nucleus (LGNd). Thus we suggest that the direction
      biases of LGNd cells are a reflection of their retinal inputs.

PMID- 7643157
TI  - Persistent current oscillations produced by activation of metabotropic glutamate
      receptors in immature rat CA3 hippocampal neurons.
AB  - 1. The single-electrode voltage-clamp technique was used to study the effects of
      the metabotropic glutamate receptors (mGluRs) agonist 1S,3R-1-aminocyclopentane
      1,3-dicarboxylic acid (1S,3R-ACPD, ACPD, 3-10 microM) on CA3 hippocampal neurons
      during the 1st 10 days of postnatal (P) life and in adulthood. 2. Repeated
      applications of 1S,3R-ACPD, in the presence of tetrodotoxin (TTX, 1 microM),
      tetraethylammonium chloride (TEACl 10 mM), and CsCl (2 mM), induced in immature
      but not in adult neurons periodic inward currents (PICs) that persisted for
      several hours after the last application of the agonist. 3. PICs, which were
      generated by nonspecific cationic currents, reversed polarity at 2.8 +/- 3 (SD)
      mV. They were reversibly blocked by kynurenic acid (1 mM), suggesting that they
      were mediated by glutamate acting on ionotropic receptors. They were also
      abolished in a nominally Ca(2+)-free medium. 4. PICs were irreversibly abolished
      by thapsigargin (10 microM) but were unaffected by ryanodine (10-40 microM).
      Caffeine (2 mM) also reversibly blocked PICs; this effect was independent from
      adenosine 3',5'-cyclic monophosphate (cAMP) accumulation, inhibition of voltage
      dependent Ca2+ current, or blockade of adenosine receptors. 5. We suggest that,
      in neonatal slices, mGluRs-induced PICs are triggered by elevation of [Ca2+]i,
      after mobilization of Ca2+ from inositol 1,4,5-trisphosphate (InsP3)-sensitive
      stores. This will lead to a persistent, pulsatile release of glutamate from
      presynaptic nerve terminals, a phenomenon that is probably maintained via a
      calcium-induced-calcium release process.

PMID- 7643158
TI  - Characterization of pharmacologically identified voltage-gated calcium channel
      currents in acutely isolated rat neocortical neurons. I. Adult neurons.
AB  - 1. Whole cell recordings were obtained from pyramidal neurons acutely dissociated
      from the sensorimotor cortex of adult rats. 2. Whole cell calcium channel
      currents were similar in appearance when elicited from holding potentials of -90
      or -40 mV. With 5 mM Ba2+ as the charge carrier, currents began to activate at
      approximately -45 mV, peaked at approximately -10 mV, and had an apparent
      reversal potential of approximately +45 mV. Current amplitude and voltage
      dependence varied with the concentration and identity of the charge carrier (Ca2+
      vs. Ba2+). Calcium channel currents were blocked completely by > 200 microM Cd2+
      (IC50 approximately 3.5 microM). 3. We determined saturating doses for blockade
      of currents by nifedipine (Nif), omega-conotoxin GVIA (CgTx), and omega-agatoxin
      IVA (AgTx) in adult cells. We also tested the selectivity of these compounds by
      applying them in combination and in different orders. We found the three
      compounds to be highly, but not perfectly, specific. 4. L-type current was
      operationally defined as that blocked by 5 microM Nif, N-type current as that
      blocked by 1 microM CgTx, and P-type current as that blocked by 100 nM AgTx. In
      adult cells, each of these compounds blocked 30-35% of the current. When all
      three blockers were applied concurrently, approximately 80% of the current was
      blocked (20% of current was resistant to the 3 blockers). 5. Few biophysical
      differences were found between the pharmacologically defined current components
      in adult cells. The resistant current had a more rapid time-to-peak, inactivated
      more rapidly and completely, and activated at more negative potentials than the
      other three types.

PMID- 7643159
TI  - Characterization of pharmacologically identified voltage-gated calcium channel
      currents in acutely isolated rat neocortical neurons. II. Postnatal development.
AB  - 1. Whole cell recordings were obtained from pyramidal neurons acutely dissociated
      from the sensorimotor cortex of adult (from Lorenzon and Foehring, companion
      paper) and immature rats postnatal day 1 (P1) to adult. 2. Whole cell calcium
      channel currents were similar in appearance at all ages. Current amplitudes and
      estimated densities were initially low (approximately 16 pA/pF at ages < P6) and
      increased gradually, attaining adult values at approximately 4-5 wk postnatally
      (approximately 100 pA/pF). 3. L-type current was operationally defined as that
      blocked by 5 microM nifedipine, N-type current as that blocked by 1 microM omega
      conotoxin GVIA, and P-type current as that blocked by 100 nM omega-agatoxin IVA.
      A resistant current remained in the presence of the combination of these three
      blockers. The proportions of these four current types did not change during
      ontogeny. 4. Few biophysical differences were found between the pharmacologically
      defined current components in adult or 1-wk-old cells. At both ages the resistant
      current had a more rapid time-to-peak and inactivated more completely and rapidly
      than the other three types. Resistant currents also activated at more negative
      potentials. N-, L-, and P-type currents activated at more positive potentials in
      1-wk-old cells than in adult cells. For the resistant current, the voltage
      dependence of activation was not significantly different between the two ages.

PMID- 7643160
TI  - Pre-Botzinger complex in the cat.
AB  - 1. Patterns of respiratory neuronal activity were examined in pentobarbitone
      anesthetized adult cats in a circumscribed area of the ventrolateral medulla,
      which has previously been defined as the pre-Botzinger complex (pre-BOTC) from
      electrophysiological and morphological criteria in the brain stem-spinal cord
      preparation of the neonatal rat. The pre-BOTC has been proposed to play a
      critical role in respiratory rhythm generation in mammals, but
      electrophysiological properties of the region have not been thoroughly
      characterized in the adult brain stem in vivo. 2. From intra- and extracellular
      recordings, we verified the existence of a well-defined zone with a distinct
      profile of neuronal activity between the rostral Botzinger complex containing
      expiratory neurons and the more caudal medullary pool of inspiratory neurons of
      the ventral respiratory group (VRG) in the para-ambigual region. This zone
      corresponds to the pre-BOTC. It was characterized by a concentration of the
      various types of respiratory neurons, particularly those proposed to be involved
      in respiratory phase transitions, including neurons discharging immediately
      before the onset of inspiratory phase activity (pre-inspiratory neurons), early
      inspiratory, and postinspiratory neurons. The majority of these neurons were
      presumed interneurons because they were not antidromically activated by spinal
      cord or cranial nerve stimulation. 3. The locus of the pre-BOTC corresponded
      histologically to the rostral part of the nucleus ambiguus and ventrolateral
      reticular formation. It was located caudal to the retrofacial nucleus and rostral
      to the lateral reticular nucleus, extending 3.0-3.5 mm rostral to the obex, and
      3.2-4.0 mm lateral from the midline. This location was homologous to that
      established in the neonatal rat. 4. Pre-inspiratory neurons (pre-I neurons) were
      specifically found in the pre-BOTC. Intracellular recordings from these neurons
      revealed two types of activity patterns. Type 1 of pre-I neurons exhibited a
      steady membrane depolarization during expiration and a steep membrane
      depolarization with a high-frequency burst of action-potential discharge during
      the phase transition from expiration to inspiration. This was followed by a
      decline of depolarization and spike discharge during the remainder of the
      inspiratory phase. A second type of pre-I neurons exhibited a secondary graded
      membrane depolarization and burst discharge during the late-inspiratory period.
      5. Synaptic events were examined in other respiratory neurons during the 40-160
      ms preceding the onset of phrenic nerve activity when pre-I neurons exhibited
      peak spike discharge. Early-inspiratory, throughout-respiratory, and
      postinspiratory neurons were disinhibited during this period, whereas stage-2
      expiratory neurons exhibited a decrease in spike activity and
      repolarization.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7643161
TI  - Laminar pattern of synaptic inhibition during convulsive activity induced by 4
      aminopyridine in neocortical slices.
AB  - 1. Epileptiform activity was induced in rat neocortical brain slices by
      application of a low concentration (10 microM) of 4-aminopyridine (4-AP). In
      intracellular recordings from regular spiking neurons, the activity was
      characterized by prolonged, all-or-none depolarizing events, with variable delay
      to a threshold stimulus. 2. At this concentration, 4-AP had no measurable effect
      on passive electrical properties or on action-potential characteristics. 3.
      Paroxysmal responses in neurons of deeper layers differed markedly from those of
      superficial cells. In deep neurons, responses resembled those generated by
      neocortical neurons exposed to GABAergic blockers. A low-intensity stimulus to
      the white matter evoked an excitatory postsynaptic potential (EPSP) that was
      followed with variable latency by a paroxysmal depolarizing shift that reversed
      at suprathreshold membrane potentials and upon which superimposed repetitive
      firing was always evident. By contrast, in superficial (layer II-III) neurons,
      the same stimulus evoked an EPSP that was followed by a prolonged response whose
      late component reversed at subthreshold membrane potentials (between -50 and -80
      mV). These cells rarely fired more than a single spike throughout the response.
      4. Repetitive stimulation at relatively low frequencies (0.3-1 Hz) caused a
      gradual change in the synchronized responses that was most marked in superficial
      neurons. The reversal potential of the response shifted toward suprathreshold
      membrane potentials, and subsequently, superimposed repetitive firing became
      evident. These changes were not associated with measurable changes in input
      resistance or membrane potential.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7643162
TI  - Modulation of rat chorda tympani nerve activity by lingual nerve stimulation.
AB  - 1. A subpopulation of lingual nerve (LN) fibers surround and/or terminate in
      taste buds in fungiform papillae. One possible function of these fibers is to
      modulate chorda tympani fiber (CT) or taste responses. To test this hypothesis,
      the rat LN was stimulated electrically at various voltages (to 20 V), and single-
      and multiunit CT responses to water-0.1 M NaCl cycles were recorded before,
      during, and after LN stimulation. 2. When a thermally controlled water-0.1 M NaCl
      stimulus cycle was applied onto the tongue's surface, the surface temperature
      remained constant, independent of the stimulation voltage. In the absence of a
      liquid stimulus, the tongue's surface temperature increased approximately 4
      degrees C upon LN stimulation for voltages > or = 5 V. This temperature increase,
      caused by vasodilation by way of the axon reflex flare mechanism, was taken as
      evidence that LN stimulation induces peptide release. 3. Comparison of CT
      activity before LN stimulation with the activity either during or after
      stimulation revealed statistically significant changes in CT activity. During LN
      stimulation the CT activity decreased. After LN stimulation, the variability in
      amount of CT activity increased. 4. In rats treated postnatally with subcutaneous
      injections of capsaicin to reduce or eliminate polymodal nociceptors, LN
      stimulation did not produce increases in the tongue's surface temperature or
      changes in CT activity. 5. Changes in CT activity could be detected seconds after
      LN stimulation, suggesting that the intragemmal and/or perigemmal LN fibers
      modulate CT activity. 6. The physiological implications of this study suggest
      that CT responses to salt can be modulated by endogenous compounds (probably
      peptides), eating foods that activate LN responses (e.g., foods that are very
      acidic or contain capsaicin) may modulate taste responses, and peri- and
      intragemmal fibers should be considered an integral part of the taste receptor
      system.

PMID- 7643163
TI  - Comparison of responses in the anterior and primary auditory fields of the ferret
      cortex.
AB  - 1. Characteristics of an anterior auditory field (AAF) in the ferret auditory
      cortex are described in terms of its electrophysiological responses to tonal
      stimuli and compared with those of primary auditory cortex (AI). Ferrets were
      barbiturate-anesthetized and tungsten microelectrodes were used to record single
      unit responses from both AI and AAF fields. Units in both areas were presented
      with the same stimulus paradigms and their responses analyzed in the same manner
      so that a direct comparison of responses was possible. 2. The AAF is located
      dorsal and rostral to AI on the ectosylvian gyrus and extends into the
      suprasylvian sulcus rostral to AI. The tonotopicity is organized with high
      frequencies at the top of the sulcus bordering the high-frequency area of AI,
      then reversing with lower BFs extending down into the sulcus. AAF contained
      single units that responded to a frequency range of 0.3-30 kHz. 3. Stimuli
      consisted of single-tone bursts, two-tone bursts and frequency-modulated (FM)
      stimuli swept in both directions at various rates. Best frequency (BF) range,
      rate-level functions at BF, FM directional sensitivity, and variation in
      asymmetries of response areas were all comparable characteristics between AAF and
      AI. Responses in both areas were primarily phasic. 4. The characteristics that
      were different between the two cortical areas were: latency to tone onset,
      excitatory bandwidth 20 dB above threshold (BW20), and preferred FM rate as
      parameterized with the centroid (a weighted average of spike counts). The mean
      latency of AAF units was shorter than in AI (AAF: 16.8 ms, AI: 19.4 ms). BW20
      measurements in AAF were typically twice as large as those found in AI (AAF: 2.5
      octaves, AI 1.3 octaves). The AI centroid population had a significantly larger
      standard deviation than the AAF centroid population. 5. We examined the
      relationship between centroid and BW20 to see whether wider bandwidths were a
      factor in a unit's ability to detect fast sweeps. There was significant (P <
      0.05) linear correlation in AAF but not in AI. In both fields the variance of the
      centroid population decreased with increasing BW20. BW20 decreased as BF
      increased for units in both auditory fields.

PMID- 7643164
TI  - Calcium hyperexcitability in neurons cultured with glutamate receptor blockade.
AB  - 1. The effects of culturing hypothalamic neurons in glutamate receptor
      antagonists were studied with fura-2 Ca2+ digital imaging of groups of
      synaptically coupled neurons. Removal of D-2-amino-5-phosphonovalerate (AP5) and
      6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) from cultures chronically blocked for
      periods of 14-188 days caused a dramatic increase in neuronal Ca2+ to abnormally
      high levels 5- to- 10 fold greater than the normal intracellular levels of 50-100
      nM. In most cases AP5/CNQX removal initiated spontaneous synchronized Ca2+
      oscillations. 2. Ca2+ rises and oscillations were blocked by the reintroduction
      of AP5/CNQX or by the addition of tetrodotoxin to block action potentials. These
      data indicate that hypothalamic neurons were the source of the excitatory
      transmitter that activated glutamate receptors and consequently led to the Ca2+
      hyperexcitability. 3. The Ca2+ spike amplitude and frequency increased in
      response to the removal of Mg2+ from the perfusion solution to facilitate N
      methyl-D-aspartate (NMDA) receptor responses. Picrotoxin, a GABAA-receptor
      blocker, also increased Ca2+ activity. 4. Blocking either NMDA (with AP5) or
      alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate-type
      (with CNQX) glutamate receptors reduced the level of Ca2+, but blocking both
      types was necessary for chronically blocked neurons to return to their basal Ca2+
      level. 5. The survival of a large percentage of chronically blocked neurons was
      dependent on the presence of glutamate receptor blockade. Removal of AP5/CNQX
      from the tissue culture medium induced an immediate increase in Ca2+ levels in
      the majority of chronically blocked neurons and, with prolonged withdrawal of
      AP5/CNQX (3 h), 50% of the neurons lost the immediate ability to regulate
      internal Ca2+ levels. Excitotoxic cell death was induced in 40% of the neurons
      within 40 h of the removal of AP5/CNQX from neurons chronically blocked for 30
      days. The number of neurons that survived for 70 days doubled when cultures were
      maintained in AP5/CNQX. 6. Relative to control cultures of the same period in
      vitro, chronically blocked neurons showed an enhanced Ca2+ influx when stimulated
      with the glutamate receptor agonists kainate (+70%), NMDA (+62%), or glutamate
      (+34%) in the presence of tetrodoxin. When the data from control and chronically
      blocked cultures stimulated with glutamate receptor agonists were pooled, without
      exception all the smallest responses were found in the control neurons. Compared
      with controls, chronically blocked neurons showed an exaggerated response to
      glutamate in the presence of nimodipine, indicating that Ca2+ hyperexcitability
      was not due to changes in voltage activated L-type Ca2+ channels.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7643166
TI  - Interaction between center and surround in rabbit retinal ganglion cells.
AB  - 1. The interaction between the center and surround mechanisms of a variety of
      rabbit retinal ganglion cell classes was examined in extracellular single-unit
      recordings in an isolated eyecup preparation. Ganglion cell classes studied
      included on and off brisk sustained and transient, on and off sluggish sustained
      and transient, on-off and on directionally selective, orientationally selective,
      and large field units. The surround effects observed were qualitatively similar
      in all these ganglion cell classes. 2. The average response-versus-contrast
      functions for stimuli within the ganglion cells' receptive-field centers were
      relatively linear between threshold and saturation for all ganglion cell classes
      examined. The major effect of surround stimulation on the center response-versus
      contrast function was a reduction in the slope of the linear portion of the
      curve, rather than a downward, parallel shift of the function. Stimulation of the
      surround had no systematically significant effect on the contrast threshold for
      the center spot, and, when it did have a significant effect, it sometimes
      decreased, rather than increased the magnitude of threshold. 3. Step changes in
      surround contrast were most effective when they were made simultaneously with
      step changes in the center; surround inhibition decreased significantly when it
      preceded stimulation of the center by > 100 ms and was generally ineffective when
      preceding the center by > 500 ms. The decrease in the inhibitory effect of
      surround stimulation was a monotonic function of delay between 0 and 500 ms. 4.
      Stimulation of the surround by step changes in the contrast of a sine-wave
      grating annulus produced qualitatively similar results to those obtained for pure
      luminance modulations. This suggests that the surround mechanism observed in
      these experiments was not due to pure luminance adaptation within the surround.
      The inhibitory effect of sine-wave gratings in the surround decreased
      monotonically as a function of spatial frequency. 5. Stimulation with a spot and
      an annulus that were both entirely within the ganglion cell's excitatory
      receptive-field center typically yielded nonadditive summation at contrasts whose
      linear sum of responses were below saturation. The effect of an annulus within
      the receptive-field center on responses elicited by a central spot quantitatively
      resembled the inhibition elicited from annuli in the inhibitory surround, after
      the excitatory center response due to the annulus was taken into account. These
      results suggest that the inhibiton elicited from the surrounds of the ganglion
      cells in these experiments extended into their receptive-field centers.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7643165
TI  - Limits on plasticity in somatosensory cortex of adult rats: hindlimb cortex is
      not reactivated after dorsal column section.
AB  - 1. To better understand the limits and extents of plasticity in sensory systems
      of adult mammals, we unilaterally sectioned the dorsal funiculus at thoracic
      levels in nine adult rats to deactivate ascending afferents from the hindpaw and
      lower body. After postsurgical recovery periods of 3 h to 3 mo, the region of
      primary somatosensory cortex (S1) representing the limbs and trunk was
      extensively mapped with microelectrodes. 2. Recording sites were later identified
      as being within the hindlimb representation and other parts of S1 by relating
      locations of microlesions to the cytochrome oxidase pattern in sections of cortex
      cut tangential to the pial surface. The extent and effectiveness of spinal cord
      lesions were evaluated by injecting cholera toxin B subunit conjugated with
      horseradish peroxidase (B-HRP) at various sites in the deafferented hindpaw. 3.
      In five animals with complete section of the dorsal funiculus, we failed to
      detect any response to cutaneous stimulation of any part of the body in the
      deafferented hindlimb cortex. In four other animals with incomplete lesions,
      neurons in some penetrations could be activated by hindlimb stimulation, but not
      by stimulating other body parts. In those cases without activation of hindlimb
      cortex, B-HRP was detected in the spinal cord only caudal to the lesion, and it
      was not transported to the nucleus gracilis. Limited transport past the lesion to
      nucleus gracilis was detected in cases with incomplete lesions. 4. The results
      indicate that forelimb inputs do not substitute for missing hindlimb inputs in
      primary somatosensory cortex in rats and that the potential for somatotopic
      reorganization is more limited than previously thought.

PMID- 7643167
TI  - Altered thermal responsiveness during regeneration of corneal cold fibers.
AB  - 1. To date, there has been no quantitative, systematic, study of the
      electrophysiology of regenerating cold receptors. This study, therefore, examines
      the changes in cold-receptor neural activity following a circular wound (5 mm
      dia, 200 microns deep) on the surface of the rabbit cornea. This is a well
      studied wounding model, in which neural regeneration has been anatomically
      quantified. 2. Extracellular recordings were obtained from a total of 90 single
      cold fibers, at 1, 3, 10, 20, or 30 days following wounding. The adapting
      temperature was 35 degrees C in all experiments. Thermal sensitivity for each
      fiber was determined by using a series of temperature steps, 0.2 degree C ranging
      from 35 to 34 degrees C, and 2 degrees C steps ranging from 35 to 24 degrees C.
      The rate of temperature change ranged from 0.2 to 1 degree C/s. 3. At the
      adapting temperature, the tonic activity of the regenerating cold-fibers was not
      significantly different from normals. Conduction velocities for regenerating cold
      fibers were slower on day 1 postwounding compared with normal fibers, 0.59 +/-
      0.04 and 0.75 +/- 0.04 (SE) M/s, respectively, however, were within the normal
      range by day 30 postwounding, 0.72 +/- 0.06 M/s. 4. On day 1, sprouting fibers
      showed decreased responsiveness to cooling (P < 0.05). At days 3 and 10
      postwounding, action potential rates in response to cooling were enhanced by 180
      200% of normal (P < 0.05) and returned to preinjury values by 20 to 30 days
      postwounding.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7643168
TI  - Involvement of substance P and neurokinin-1 receptors in the hyperexcitability of
      dorsal horn neurons during development of acute arthritis in rat's knee joint.
AB  - 1. In anesthetized rats we studied the involvement of substance P and neurokinin
      1 receptors in the generation and maintenance of hyperexcitability in spinal cord
      neurons, which develops in the course of an acute experimental inflammation in
      the knee. In all experiments one nociceptive neuron with knee input was
      identified, and the responses to mechanical stimuli and the receptive fields were
      monitored before and after induction of inflammation by the injections of kaolin
      and carrageenan into the knee joint. In 18 experiments either the specific
      antagonist at the neurokinin-1 receptor ionophoretically close to the neuron or
      intravenously during the injections of kaolin and carrageenan and in three
      periods of 15 min in the 95 min postkaolin (initial period of inflammation) to
      test their effects on the development of hyperexcitability. CP96,345 and CP96,344
      were also administered after full development of inflammation to study their
      effects in hyperexcitable neurons. CP96,345 was ejected at currents that reduced
      or completely suppressed the effects of ionophoretically administered substance P
      but not those of neurokinin A, the agonist at neurokinin-2 receptors. 2. After
      the injections of kaolin and carrageenan into the knee joint, untreated control
      neurons (n = 8) developed hyperexcitability consisting of enhanced responses to
      noxious stimuli applied to the injected knee and the noninjected ankle, of an
      enhancement or induction of the responses to innocuous pressure applied to the
      joints and of an expansion of the receptive field. In eight neurons treated with
      ionophoretic administration of CP96,345 during the induction and initial period
      of inflammation, the development of hyperexcitability was not completely
      prevented but significantly attenuated. In comparison with the changes in the
      control neurons, the development of hyperexcitability was markedly reduced from
      the 2nd h up to 5 h postkaolin, but it was barely affected by CP96,345 within the
      1st h postkaolin. Intravenous administration of CP96,345 in the initial period of
      inflammation produced a similar reduction of the development of hyperexcitability
      in another four neurons. The ionophoretic application of CP96,344 during and
      after induction of inflammation did not apparently impair the development of
      hyperexcitability (n = 6 neurons). 3. After development of inflammation and
      hyperexcitability, both the responses to innocuous and noxious pressure applied
      to the inflamed knee joint were reduced by the ionophoretic (n = 16 neurons) and
      intravenous administration (n = 9 neurons) of CP96,345 (tested 4.5-8 h
      postkaolin). Similarly, the responses to innocuous and noxious pressure applied
      to the noninflamed ankle were reduced by CP96,345 after inflammation had
      developed in the knee joint.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7643169
TI  - Influence of VPM afferents on putative inhibitory interneurons in S1 of the awake
      rabbit: evidence from cross-correlation, microstimulation, and latencies to
      peripheral sensory stimulation.
AB  - 1. Responses of thalamocortical projection neurons and suspected cortical
      interneurons (SINs) to very brief peripheral stimuli were examined within the
      vibrissae, the sinus hair, the lip, and the chin representations of
      ventroposterior medial thalamus (VPM) and primary somatosensory cortex (S1). VPM
      thalamocortical neurons (N = 40) were identified by their antidromic activation
      after electrical stimulation of S1. SINs were identified by a high-frequency (>
      600 Hz) burst of three or more spikes elicited by suprathreshold stimulation of
      one or more afferent pathways. SINs also had spikes of very short duration. 2.
      Previous work has shown that electrical stimulation of VPM elicits a very early
      and powerful synaptic response in many S1 SINs. Three experimental strategies
      were employed to test the hypothesis that such responses reflect a monosynaptic
      VPM input onto SINs and to examine the effects of such input. 1) After a brief
      peripheral stimulus, the arrival times of VPM thalamocortical impulses in S1 were
      determined and compared with the initial response times of S1 SINs. 2) Shift
      corrected cross-correlograms (CCGs) were constructed from the spike trains of
      pairs of VPM neurons and SINs that were in precise topographic alignment. 3)
      Inferences of connectivity based on such CCGs were supported by applying very low
      intensity (1-10 microA) microstimulation pulses to the recording microelectrode
      in VPM and observing evoked responses in the cortical SIN. 3. VPM thalamocortical
      neurons responded to a brief air puff stimulus at a median latency of 5.05 ms,
      and the estimated arrival time of the VPM impulses at S1 had a median value of
      5.97 ms. This estimate was obtained by adding the antidromic latency of each VPM
      neuron to the latency of the peripheral stimulus and was supported by similar
      values obtained from three VPM thalamocortical axons recorded near their
      termination site within S1. SINs of S1 were among the first cortical neurons to
      respond to the peripheral stimulus, responding to the air puff at a median
      latency of 6.6 ms (range 5.7-13.0 ms). The latency of SINs to the peripheral
      stimulus was strongly related to the latency to gross electrical stimulation of
      VPM (median value 1.52 ms, r2 = +0.44, P < 0.0001). Many SINs (23 of 34) showed
      significant shift-corrected CCGs with VPM neurons that were in precise
      topographic alignment. Most significant CCGs revealed a very brief increase in
      SIN spike probability (half-amplitude response of approximately 1 ms) that
      reached a peak value at intervals of 1.4-2.0 ms after the VPM spike.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7643170
TI  - Transformation of temporal discharge patterns in a ventral cochlear nucleus
      stellate cell model: implications for physiological mechanisms.
AB  - 1. We have stimulated responses of stellate cells in the anteroventral cochlear
      nucleus (AVCN) to single-formant stimuli (SFSs) with the use of recorded auditory
      nerve fiber (ANF) responses as inputs. In particular, two important features of
      temporal discharge patterns, the phase locking to best frequency (BF) tones and
      to stimulus envelopes, were examined in the model output. Our earlier
      experimental studies with SFSs found an enhancement of the envelope modulation in
      AVCN chopper units, presumably recorded from stellate cells, as compared with
      that of ANFs. 2. We simulated in the model three mechanisms for the enhancement
      in envelope modulation proposed earlier by us, namely, convergence of ANFs,
      temporal summation and inhibitory input. It was found that the convergence of
      multiple ANFs alone did not always lead to an enhancement in modulation depth,
      but was necessary for the model to produce other physiologically plausible
      envelope features; the temporal summation of subthreshold events can lead to an
      increase in modulation depth; and the somatic inhibition effectively reduced the
      envelope minimum and, as a result, increased the modulation depth. In addition,
      we found that, given the same input configuration, the closer the inputs were
      located to the soma, the greater modulation depth they produced at the model
      output. 3. Different types of convergence of ANF inputs were tested in our model.
      It was found that the convergence of both low and high spontaneous rate (SR) ANFs
      resulted in an enhancement in modulation depth over a wider range of sound level
      than that due to the convergence of ANFs from the same SR group.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7643171
TI  - Spinal plasticity after hemilabyrinthectomy and its relation to postural recovery
      in the frog.
AB  - 1. Brachial dorsal root-evoked ventral root responses were studied in the
      isolated brain/spinal cord preparation of frogs. One group of frogs (n = 20) had
      survived a hemilabyrinthectomy (HL) between 7 and 70 days. In another group of
      frogs (n = 30), a nerve branch to an individual labyrinthine organ was sectioned
      uni- or bilaterally 15 days before the recording session. In a third group of
      frogs (n = 5), a weight had been mounted eccentrically on the head for 15 days. A
      fourth group of intact frogs (n = 8) served as a control. 2. In chronic HL frogs
      (> or = 60 days postoperatively) the amplitudes of short- and long-latency
      ventral root potentials recorded on the operated side were consistently increased
      with respect to control values in response to all converging inputs tested. On
      the intact side most of these potentials were consistently increased as well,
      except for crossed long-latency responses after stimulation of the dorsal root on
      the operated side. 3. Practically identical responses were recorded in these
      preparations before and after the disconnection of the spinal cord from the brain
      stem at the level of the obex. Before this disconnection, ventral root potentials
      were recorded in response to electric stimulation of either one of the VIIIth
      nerves on the intact or on the operated side. Ventral root potentials recorded on
      the operated but not on the intact side were slightly increased in chronic HL
      frogs. 4. The time course of these changes was studied at intervals between 7 and
      70 days after the lesion. The amplitudes of short-latency dorsal root-evoked
      ventral root potentials were increased relatively early (7-15 days) or relatively
      late (> or = 30 days) after HL. Ventral root potentials evoked by stimulation of
      either one of the N.VIII were significantly reduced in amplitude seven days after
      HL but normalized again or increased above control values after longer survival
      periods. These differences in the time courses suggest the presence of multiple,
      not singular mechanisms for intraspinal changes. 5. Changes in dorsal root-evoked
      ventral root potentials similar to those after HL were seen 15 days after a
      selective unilateral section of the utricular, but not after a unilateral section
      of the horizontal canal or saccular nerve branch. Therefore these changes were
      initiated either by asymmetric utricular afferent inputs or by asymmetric
      proprioceptive inputs resulting from lesion-induced postural deficits. 6. These
      two possibilities were investigated in two different sets of
      experiments.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7643172
TI  - Rapid horizontal gaze movement in the monkey.
AB  - 1. We studied horizontal eye and head movements in three monkeys that were
      trained to direct their gaze (eye position in space) toward jumping targets while
      their heads were both fixed and free to rotate about a vertical axis. We
      considered all gaze movements that traveled > or = 80% of the distance to the new
      visual target. 2. The relative contributions and metrics of eye and head
      movements to the gaze shift varied considerably from animal to animal and even
      within animals. Head movements could be initiated early or late and could be
      large or small. The eye movements of some monkeys showed a consistent decrease in
      velocity as the head accelerated, whereas others did not. Although all gaze
      shifts were hypometric, they were more hypometric in some monkeys than in others.
      Nevertheless, certain features of the gaze shift were identifiable in all
      monkeys. To identify those we analyzed gaze, eye in head position, and head
      position, and their velocities at three points in time during the gaze shift: 1)
      when the eye had completed its initial rotation toward the target, 2) when the
      initial gaze shift had landed, and 3) when the head movement was finished. 3. For
      small gaze shifts (< 20 degrees) the initial gaze movement consisted entirely of
      an eye movement because the head did not move. As gaze shifts became larger, the
      eye movement contribution saturated at approximately 30 degrees and the head
      movement contributed increasingly to the initial gaze movement. For the largest
      gaze shifts, the eye usually began counterrolling or remained stable in the orbit
      before gaze landed. During the interval between eye and gaze end, the head alone
      carried gaze to completion. Finally, when the head movement landed, it was almost
      aimed at the target and the eye had returned to within 10 +/- 7 degrees, mean +/-
      SD, of straight ahead. Between the end of the gaze shift and the end of the head
      movement, gaze remained stable in space or a small correction saccade occurred.
      4. Gaze movements < 20 degrees landed accurately on target whether the head was
      fixed or free. For larger target movements, both head-free and head-fixed gaze
      shifts became increasingly hypometric. Head-free gaze shifts were more accurate,
      on average, but also more variable. This suggests that gaze is controlled in a
      different way with the head free. For target amplitudes < 60 degrees, head
      position was hypometric but the error was rather constant at approximately 10
      degrees.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7643173
TI  - Structural and functional differences distinguish principal from nonprincipal
      cells in the guinea pig MSO slice.
AB  - 1. Principal cells in the medial superior olive (MSO) receive low-frequency
      information from both ears via left and right cochlear nuclei. In vivo
      extracellular records suggest that some MSO neurons respond optimally only when
      the binaural acoustic signal has a precise interaural delay. Thus MSO cells, in
      particular principal cells, are thought to be the first stage in the processing
      of interaural time difference cues that provides information as to the location
      of a low-frequency sound in space. 2. Despite this proposed fundamental role for
      the MSO, certain features of this nucleus make in vivo recordings from any cell
      type here very difficult to obtain. Only a small number of extracellular records
      and no intracellular recordings are reported in the literature. Using sharp,
      neurobiotin-filled glass electrodes to record intracellularly from cells in an in
      vitro brain slice of the guinea pig superior olivary complex, I have begun to
      assess the anatomic and physiological features of cells in the MSO that might be
      relevant to such a functional role in vivo. 3. Two basic MSO cell types,
      designated principal and nonprincipal, could be distinguished on the basis of
      certain anatomic and physiological differences. 4. Labeled principal cell bodies
      were located at all dorsoventral location within the MSO. Labeled nonprincipal
      cells were located in or around the dorsal aspects of the nucleus. Principal
      cells typically had thick bipolar dendrites (1 directed medially, 1 laterally)
      that did not taper or branch significantly except at their terminations.
      Nonprincipal cells were multipolar with three to nine thinner primary dendrites
      that did not branch preferentially in a mediolateral direction. Principal cell
      axons gave off collaterals terminating in and around the dorsal MSO. Nonprincipal
      cells also had axon in and around the dorsal MSO. Nonprincipal cells also had
      axon collateral branches innervating dorsal MSO, but these axons could branch
      more extensively and project further down the dorsoventral aspect of the nucleus.
      5. Principal cells typically responded to depolarizing current pulses with one or
      a few spikes at current onset. When bathed in saline containing 4-aminopyridine
      (4-AP), they fired repetitively to the same depolarizing current pulses. This
      would indicate a depolarization-induced nonlinearity similar to that seen in
      principal cell types of two other auditory brain stem nuclei, the anteroventral
      cochlear nucleus and medial nucleus of the trapezoid body. Nonprincipal cells
      normally fired repetitively to depolarizing current pulses even close to spike
      threshold. Both cell types could show a sag in the membrane potential to
      hyperpolarizing current pulses.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7643174
TI  - Neurons sensitive to interaural phase disparity in gerbil superior olive: diverse
      monaural and temporal response properties.
AB  - 1. We assessed mechanisms of binaural interaction underlying detection of
      interaural phase disparity (IPD) by recording single-unit responses in the
      superior olivary complex (SOC) of the anesthetized gerbil (Meriones
      unguiculatus). Binaural responses were obtained from 58 IPD-sensitive single
      units, 44 of which were histologically localized. Monaural responses were also
      obtained for 52 of 58 IPD-sensitive units. Additionally, responses were recorded
      from 16 units (best frequency < 2.4 kHz) in lateral SOC that were excited by
      ipsilateral stimulation and inhibited by contralateral stimulation (EI), none of
      which was IPD sensitive. Our results are consistent with a mechanism of binaural
      interaction involving detection of coincident excitatory inputs from the two
      ears. There was no compelling evidence of binaural sensitivity arising from IPD
      dependent interactions of phase-locked excitatory and inhibitory inputs from the
      two ears. Despite the uniformity of binaural interactions, considerable diversity
      of temporal and monaural response properties was observed. 2. Monaural and
      binaural responses of 35 of 58 IPD-sensitive units were phase locked to the
      period of low-frequency (< 2.5 kHz) tones. Most phase-locking units were
      bilaterally excitable and, consistent with the coincidence-detection model, their
      IPD selectivity could be predicted from the difference between the mean phases of
      the monaural responses. The remaining units (23 of 58) did not phase lock in
      response to monaural or binaural tones. Most non-phase-locking units failed to
      respond to monaural stimulation of one or both ears (monaurally unresponsive
      units). 3. Some IPD-sensitive units were inhibited by monaural stimulation of the
      ipsilateral ear or both ears. A few units responded only at the onset of monaural
      and binaural tones. Phase locking was present in responses of some, but not all,
      of these monaurally inhibited and onset units. 4. Most IPD-sensitive neurons were
      encountered at sites within or immediately adjacent to the cell column of the
      medial superior olive (MSO). IPD-sensitive units were also recorded in the
      lateral superior olive (LSO), in the superior paraolivary nucleus (SPN), and
      within a region forming a medial-dorsal cap around MSO. Bilaterally excitable
      unites were concentrated around MSO, but were also encountered in SPN, the medial
      dorsal region, and LSO. Some monaurally unresponsive units were recorded in the
      vicinity of the MSO, but most were located in the medial-dorsal region.
      Monaurally inhibited units were localized to the medial border of the MSO cell
      column or to SPN. Onset units were localized to SPN and the medial-dorsal region.
      EI units were located exclusively in LSO.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7643175
TI  - Dentate EEG spikes and associated interneuronal population bursts in the
      hippocampal hilar region of the rat.
AB  - 1. This paper describes two novel population patterns in the dentate gyrus of the
      awake rat, termed type 1 and type 2 dentate spikes (DS1, DS2). Their cellular
      generation and spatial distribution were examined by simultaneous recording of
      field potentials and unit activity using multiple-site silicon probes and wire
      electrode arrays. 2. Dentate spikes were large amplitude (2-4 mV), short duration
      (< 30 ms) field potentials that occurred sparsely during behavioral immobility
      and slow-wave sleep. Current-source density analysis revealed large sinks in the
      outer (DS1) and middle (DS2) thirds of the dentate molecular layer, respectively.
      DS1 and DS2 had similar longitudinal, lateral, and interhemispheric synchrony. 3.
      Dentate spikes invariably were coupled to synchronous population bursts of
      putative hilar interneurons. CA3 pyramidal cells, on the other hand were
      suppressed during dentate spikes. 4. After bilateral removal of the entorhinal
      cortex, dentate spikes disappeared, whereas sharp wave-associated bursts,
      reflecting synchronous discharge of the CA3-CA1 network, increased several fold.
      5. These physiological characteristics of the dentate spikes suggest that they
      are triggered by a population burst of layer II stellate cells of the lateral
      (DS1) and medial (DS2) entorhinal cortex. 6. We suggest that dentate spike
      associated synchronized bursts of hilar-region interneurons provide a suppressive
      effect on the excitability of the CA3-CA1 network in the intact brain.

PMID- 7643176
TI  - Recurrent spontaneous seizure activity in hippocampal neuronal networks in
      culture.
AB  - 1. Experiments were carried out using intracellular recording techniques on
      hippocampal neurons maintained in culture to determine if populations of
      hippocampal neurons could be induced to develop spontaneously recurring
      epileptiform discharges. This study demonstrates the conversion of normal
      hippocampal neurons in culture by a brief Mg(2+)-free treatment into a
      preparation of cells that permanently manifested recurrent, spontaneous seizure
      discharges. These electrographic seizure discharges illustrated the same
      electrographic properties seen in human epilepsy and were observed for the life
      of the culture. 2. The epileptic activity was shown to occur synchronously in
      populations of neurons and to be controlled by clinically useful anticonvulsant
      drugs. 3. This new cell culture model of epileptic activity provides a powerful
      tool to investigate the molecular mechanisms underlying the induction,
      maintenance, and termination of this "epileptic condition" in vitro and
      demonstrates that neuronal networks in culture can be transformed to manifest
      permanently spontaneous recurrent electrographic seizures.

PMID- 7643177
TI  - Brevity of processing in a mnemonic task.
AB  - 1. A burst of from one to four current pulses of 0.2 ms at 100 Hz was
      administered bilaterally to medial temporal lobe areas while monkeys worked in a
      delayed matching-to-sample visual memory task. The brief electrical stimulation
      was used as a probe to determine when, around the 20 or 50 ms sample
      presentation, the disruption was most severe. 2. Stimulation within about 200 ms
      of the sample image onset severely perturbed the animals' ability subsequently to
      recognize that image. Identical stimulation at other times did not. 3. Thus, the
      processing during encoding, that is accessible to the implanted medial temporal
      lobe electrodes, appears to occur only in a brief interval associated with
      receipt of the sensory input.

PMID- 7643178
TI  - Lesion of the nodulus and ventral uvula abolish steady-state off-vertical axis
      otolith response.
AB  - 1. During rotations that dynamically activate utricular and saccular primary
      afferents, the otolith system centrally detects the velocity and direction of
      rotation of the head in space. This property is experimentally manifested as a
      steady-state compensatory nystagmus during constant velocity off-vertical axis
      rotations. The computational, physiological, and anatomic details of this
      response remain presently unknown. Here we report that surgical inactivation of
      the cerebellar nodulus and ventral uvula abolished the ability of the otolith
      system to generate steady-state nystagmus during constant velocity rotation and
      to improve the dynamics of the vestibuloocular reflex (VOR) during low-frequency
      sinusoidal oscillations about off-vertical axes in rhesus monkeys. These results
      suggest that the cerebellar nodulus and/or ventral uvula comprise part of the
      neural substrate that is involved in these computations.

PMID- 7643179
TI  - Effects of nerve injury on sympathetic excitation of A delta mechanical
      nociceptors.
AB  - 1. The effects of sympathetic stimulation and close arterial injection of
      norepinephrine were tested on cutaneous myelinated-fiber (A delta) mechanical
      nociceptors [high-threshold mechanoreceptors-(MyHTMs)] from normal and from
      partially transsected nerves. 2. Neither sympathetic stimulation nor close
      arterial injection of norepinephrine (200 ng) excited MyHTMs (18) recorded from
      the uninjured great auricular nerve of adult rabbits. 3. MyHTMs (58) conducting
      across the site of partial cut lesions, made 2 to 28 days previously, had
      threshold and responsiveness to mechanical stimuli, receptive field organization,
      and absence of background discharge typical of such elements in normal nerve. 4.
      Four MyHTMs recorded from the injured nerves were excited by sympathetic
      stimulation and/or norepinephrine injection but only one gave more than two
      impulses within 60 s to either form of stimulation. 5. The meagerness of the
      sympathetic and adrenergic excitation of MyHTMs after nerve injury contrasts with
      that observed under similar conditions for C-fiber polymodal nociceptors.
      Therefore, induction of adrenergic responsiveness in nociceptors after partial
      denervation in cutaneous MyHTMs appears to be less important for mechanisms
      related to pathogenic pain than alterations in certain C-fiber nociceptors.

PMID- 7643180
TI  - Modified saccades evoked by stimulation of the macaque superior colliculus
      account for properties of the resettable integrator.
AB  - 1. Models of the saccadic system propose that there is an integration of the
      pulse signal, and there is good evidence that the integrator is reset gradually
      (Nichols and Sparks 1994, 1995). Other studies of the superior collicular
      contribution to the saccadic system have proposed a sensory, not motor, nature
      for its signal. 2. To test experimentally the resetting of the integrator and the
      nature of the collicular signal, we electrically stimulated the superior
      colliculus during periods of fixation and during the course of visually guided
      saccades. Trains of stimuli which were presented during periods of fixation
      evoked saccades with fixed vectors. Identical stimulation at the beginning of a
      visually guided saccade evoked saccades whose direction was rotated and amplitude
      extended from the fixed vector. The direction of the rotation was opposite that
      of the visually guided saccade, and the magnitude of this rotation could be as
      large as 80 degrees. 3. Stimulation which was applied at progressively later
      times during the visually guided saccade, evoked saccades with progressively
      smaller rotations and progressively less elongations. The time period during
      which saccades were modified persisted beyond the end of the visually guided
      saccade, when the eyes were stationary. Thus, we confirm the previous findings
      (Nichols and Sparks 1994, 1995; Robinson, 1972), that the end of the saccade is
      not a period of quiescence within the oculomotor pathways. 4. Our results confirm
      that the resetting of the integration of the saccade signal is gradual rather
      than abrupt. Furthermore, these data suggest that the superior colliculus signals
      a motor error.

PMID- 7643181
TI  - Early childhood caries: a continuing dilemma.
AB  - Early childhood caries continues to be a problem in the U.S. This paper examines
      the progression, etiology, prevention and treatment of this condition. A
      suggested future direction for research and governmental action needed to combat
      this expensive and debilitating condition is presented. The author recognizes all
      that the CDA has done and is doing to help prevent this debilitating oral disease
      in California.

PMID- 7643182
TI  - Preventive dentistry for pediatric patients.

PMID- 7643183
TI  - Fluoride content of Los Angeles County water.
AB  - A series of tap water samples were collected from residents in various areas of
      Los Angeles County. Three samples were collected each week over a period of three
      weeks, for a total of nine samples from each of the 45 residences. Samples were
      analyzed for fluoride content, and the data compared to information received from
      the agencies supplying the source water. Fluoride levels varied an average of .11
      ppm during the three-week collection period; mean levels were consistently higher
      than values reported by the various agencies.

PMID- 7643184
TI  - Expected caries preventive benefits of fluoridating L.A. water supplies.
AB  - Water fluoridation at the optimal concentration for the geographic area confers
      the maximum decay preventive benefits. Numerous communities have suboptimal
      levels of naturally occurring fluoride. The question of how much additional
      caries preventive benefits would be obtained if these communities fluoridate is
      of more than academic interest. Using Los Angeles as an example, this paper
      estimates the additional caries preventive benefits that may be realized in
      adjusting the fluoride concentration to the ideal.

PMID- 7643185
TI  - Economics vs. accountability.

PMID- 7643186
TI  - Clearly revolting.

PMID- 7643187
TI  - Chowing down with gram.

PMID- 7643188
TI  - The value of the hands-on learning experience.

PMID- 7643189
TI  - Temporomandibular dysfunction, chronic orofacial pain and oral motor disorders in
      the 21st century.
AB  - This article describes the various sensory and motor disorders that afflict the
      orofacial region. These abnormalities are broadly separated into three groups of
      pathologic conditions: temporomandibular disorders; chronic orofacial pain
      disorders; and oral motor disorders. This article focuses on the diagnostic
      features of each specific disorder, suggesting alternate nomenclature for each
      disorder.

PMID- 7643190
TI  - The anatomy of local anesthesia.
AB  - The trigeminal nerve is the great sensory nerve of the facial portion of the
      head, and an intimate knowledge of this nerve and its surrounding structures is a
      prerequisite to the application of structures is a prerequisite to the
      application of profound local anesthesia without complication. In this review
      article, the classic description of the relevant anatomy is presented and updated
      with recently published research into anatomic variations that have an impact on
      the induction of clinical local anesthesia. Causes of both failure and
      complications of traditional local anesthetic techniques are explained, and
      recommendations for avoiding these pitfalls are made.

PMID- 7643191
TI  - Treatment of post-operative pain.
AB  - The effectiveness of three treatments for alveolar osteitis was compared. It was
      found that chlorhexidine gluconate mouthwash treatment and 2.5 percent Lidocaine
      ointment treatment reduced the number of days a patient was symptomatic compared
      to the conventional eugenol-impregnated iodoform gauze treatment. With the
      conventional use of eugenol-impregnated iodoform gauze, the severity of the
      patient's symptoms were reduced more effectively than with the other two
      treatments, but the symptoms lasted longer.

PMID- 7643192
TI  - Rod photoreceptor neurite sprouting in retinitis pigmentosa.
AB  - In animal models for retinitis pigmentosa (RP), rod photoreceptors show abnormal
      distribution of rhodopsin prior to undergoing cell death. To elucidate the steps
      in degeneration of human photoreceptors, immunocytochemistry was performed on
      donor retinas from 15 RP patients and five normal subjects. Rhodopsin
      immunolabeling in the normal retinas was restricted to the rod outer segments. In
      the RP retinas, rhodopsin was present in shortened rod outer segments and in the
      surface membranes of the rod inner segments and somata. In regions of
      photoreceptor death, the surviving rods had sprouted rhodopsin-positive neurites
      that were closely associated with gliotic Muller cell processes and extended to
      the inner limiting membrane. Rods and cones in the RP maculas did not form
      neurites, but the axons of peripheral cones were abnormally elongated and
      branched. Double immunofluorescence labeling showed that the rod neurites
      bypassed the horizontal and rod bipolar cells that are normally postsynaptic to
      rod axons. To our knowledge, this is the first report of rod neurite sprouting in
      vivo. We were unable to find neurites on degenerate rods in old rds mice, an
      animal model for RP. The rod neurites in the human RP retinas resemble the long,
      branched processes formed by rods cultured on Muller cells or purified N-CAM.
      Neurite growth by surviving rods in the RP retinas may be a response to
      neurotrophic factor upregulation, loss of inhibitory factors, or changes in
      molecules associated with reactive Muller cells. Such changes in the retinal
      microenvironment may impede functional integration of transplanted
      photoreceptors. The contributions of the rhodopsin-positive rod neurites and
      abnormal cone axons to the functional abnormalities observed in RP are unknown.

PMID- 7643193
TI  - Increase of extracellular corticotropin-releasing factor-like immunoreactivity
      levels in the amygdala of awake rats during restraint stress and ethanol
      withdrawal as measured by microdialysis.
AB  - Previous research has suggested a role for corticotropin-releasing factor (CRF)
      in the anxiogenic effects of stressful stimuli and ethanol withdrawal. This
      hypothesis was explored in a series of experiments using intracranial
      microdialysis to monitor CRF-like immunoreactivity (CRF-IR) in the extracellular
      compartment of the rat amygdala. The synaptic origin of CRF-IR release in the
      amygdala was determined in vitro by assessing the Ca2+ dependency of 4
      aminopyridine stimulated CRF-IR release from tissue preparations of rat amygdala.
      In vivo experiments were performed in awake rats after the placement of
      microdialysis probes in the amygdala. In the first experiment, transient
      restraint stress (20 min) produced an increase of CRF-IR release (basal levels,
      1.19 +/- 0.15 fmol/50 microliters; stress levels, 4.54 +/- 1.33 fmol/50
      microliters; p < 0.05) that returned to basal values within 1 hr. When 4
      aminopyridine (5 mM) was added to the perfusion medium, it consistently increased
      CRF-IR release (4.83 +/- 0.92 fmol/50 microliters, p < 0.05). In the second
      experiment, CRF-IR release was measured during ethanol withdrawal in rats
      previously maintained for 2-3 weeks on a liquid diet containing ethanol (8.5%).
      Basal CRF-IR levels were 2.10 +/- 0.43 fmol/50 microliters in ethanol exposed
      rats and 1.30 +/- 0.19 fmol/50 microliters in control rats. During withdrawal, a
      progressive increase of CRF-IR levels over time was observed, reaching peak
      values at 10-12 hr after the onset of withdrawal (10.65 +/- 0.49 fmol/50
      microliters vs 1.15 +/- 0.30 fmol/50 microliters of control rats, p <
      0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7643194
TI  - An emergent model of orientation selectivity in cat visual cortical simple cells.
AB  - It is well known that visual cortical neurons respond vigorously to a limited
      range of stimulus orientations, while their primary afferent inputs, neurons in
      the lateral geniculate nucleus (LGN), respond well to all orientations.
      Mechanisms based on intracortical inhibition and/or converging thalamocortical
      afferents have previously been suggested to underlie the generation of cortical
      orientation selectivity; however, these models conflict with experimental data.
      Here, a 1:4 scale model of a 1700 microns by 200 microms region of layer IV of
      cat primary visual cortex (area 17) is presented to demonstrate that local
      intracortical excitation may provide the dominant source of orientation-selective
      input. In agreement with experiment, model cortical cells exhibit sharp
      orientation selectivity despite receiving strong iso-orientation inhibition, weak
      cross-orientation inhibition, no shunting inhibition, and weakly tuned
      thalamocortical excitation. Sharp tuning is provided by recurrent cortical
      excitation. As this tuning signal arises from the same pool of neurons that it
      excites, orientation selectivity in the model is shown to be an emergent property
      of the cortical feedback circuitry. In the model, as in experiment, sharpness of
      orientation tuning is independent of stimulus contrast and persists with
      silencing of ON-type subfields. The model also provides a unified account of
      intracellular and extracellular inhibitory blockade experiments that had
      previously appeared to conflict over the role of inhibition. It is suggested that
      intracortical inhibition acts nonspecifically and indirectly to maintain the
      selectivity of individual neurons by balancing strong intracortical excitation at
      the columnar level.

PMID- 7643195
TI  - Presynaptic differentiation induced in cultured neurons by local application of
      basic fibroblast growth factor.
AB  - Recent studies have suggested a role for molecules residing at the muscle surface
      in signaling presynaptic development at the neuromuscular junction (NMJ). Since
      heparan sulfate-proteoglycan is a major component of the extracellular matrix of
      skeletal muscle, factors that are bound to this proteoglycan, such as basic
      fibroblast growth factor (bFGF), are in a strategic position for neuronal
      signaling. To test this idea, we applied bFGF to cultured Xenopus spinal cord
      neurons and monitored the change in intracellular Ca2+ level with fura-2 ratio
      imaging. In one-third of the neurons, local application of bFGF elicited a 30
      140% increase in intracellular Ca2+ level. Ca(2+)-free medium or suramin
      abolished this change. Latex beads coated with bFGF induced clustering of
      synaptic vesicles at the bead-neurite contacts as evidenced by anti-synaptotagmin
      antibody labeling and electron microscopy. This response was also blocked by
      Ca(2+)-free medium and by suramin. Uncoated beads or beads coated with PDGF were
      ineffective. This induction was also inhibited by a tyrosine kinase inhibitor,
      tyrphostin RG-50864, suggesting the role of receptor tyrosine kinase activation
      in this process. In addition, bFGF-coated beads also induced the localization of
      depolarization-dependent Ca2+ influx to the bead-neurite contacts. In contrast,
      depolarization caused a distributed Ca2+ elevation in untreated neurites. These
      results suggest that local presentation of bFGF can mimic the muscle target in
      signaling the development of both a cytoplasmic and a membranous specialization
      for excitation-secretion coupling observed at the NMJ.

PMID- 7643196
TI  - Reorganization of ascending 5-HT axon projections in animals previously exposed
      to the recreational drug (+/-)3,4-methylenedioxymethamphetamine (MDMA,
      "ecstasy").
AB  - The recreational drug (+/)3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") is
      a methamphetamine derivative that selectively destroys central 5-HT axons and
      axon terminals in animals and, possibly, humans. The fate of 5-HT neurons
      following MDMA injury is uncertain. In particular, while it is known that central
      5-HT axons can undergo regenerative sprouting after MDMA injury, it has not been
      determined whether they reestablish the original innervation pattern. To address
      this question, the present studies examined 5-HT innervation patterns in animals
      lesioned with MDMA 12-18 months previously. Both rodents (rats) and nonhuman
      primates (squirrel monkeys) were examined, since there is indication that
      serotonergic recovery after MDMA injury may be species dependent. 5-HT axon
      projections were studied neurochemically, autoradiographically and
      immunocytochemically. In both rodents and nonhuman primates previously lesioned
      with MDMA, substantial serotonergic axonal sprouting was observed. However, in a
      few rats and in most squirrel monkeys, the reinnervation pattern was highly
      abnormal: distant targets (e.g., dorsal neocortex) remained denervated, while
      some proximal targets (e.g., amygdala, hypothalamus) were reinnervated or
      hyperinnervated. Although the specific determinants of axonal recovery after MDMA
      injury remain to be identified, it appears that axons which initially sustain
      more severe damage, are longer, or are more highly arborized have low probability
      of recovering. The observation that some brain regions remain denervated, while
      others are reinnervated or hyperinnervated suggests that, under some
      circumstances, MDMA injury can lead to a lasting reorganization of ascending 5-HT
      axon projections. Such lasting changes in brain innervation, documented here in
      MDMA-treated animals, may have implications for humans using MDMA recreationally.

PMID- 7643197
TI  - Thalamocortical projections have a K+ channel that is phosphorylated and
      modulated by cAMP-dependent protein kinase.
AB  - The finding that some K+ channel mRNAs are restricted to certain populations of
      neurons in the CNS suggests that there are K+ channels tailored to certain
      neuronal circuits. One such example are the transcripts from the KV3.2 gene, the
      majority of which are expressed in thalamic relay neurons. To gain insights into
      the specific roles of KV3.2 subunits, site specific antibodies were raised to
      determine their localization in thalamic relay neurons. Immunohistochemical and
      focal lesioning studies demonstrate that KV3.2 proteins are localized to the
      terminal fields of thalamocortical projections. It is also shown that KV3.2
      channels expressed in vitro are strongly inhibited through phosphorylation by
      cAMP-dependent protein kinase (PKA). Channels containing KV3.1 subunits, which
      otherwise exhibit nearly identical electrophysiological properties in
      heterologous expression systems but have a different and less restricted pattern
      of expression in the CNS, are not affected by PKA. Therefore, this modulation
      might be associated with the specific roles of KV3.2 subunits. Furthermore, we
      demonstrate that KV3.2 proteins can be phosphorylated in situ by intrinsic PKA.
      KV3.2 subunits display properties and have a localization consistent with a role
      in the regulation of the efficacy of the thalamocortical synapse, and could
      thereby participate in the neurotransmitter-mediated control of functional states
      of the thalamocortical system associated with global states of awareness.

PMID- 7643198
TI  - Two factors secreted by the goldfish optic nerve induce retinal ganglion cells to
      regenerate axons in culture.
AB  - Unlike mammals, lower vertebrates can regenerate an injured optic nerve and other
      pathways of the CNS throughout life. We report here that in dissociated cell
      culture, goldfish retinal ganglion cells regenerate their axons in response to
      two factors derived from the sheath cells of the optic nerve. Axogenesis factor 1
      (AF-1) is a small peptide (700-900 Da) that is inactivated by treatment with
      proteinase K but heat stable. A second factor, AF-2, is a polypeptide of ca 12
      kDa. In the absence of these factors, dissociated retinal cells remained viable
      in serum-free, defined media for at least a week but showed little outgrowth, as
      visualized using the vital dye 5,6-carboxyfluorescein diacetate (5,6-CFDA). The
      addition of AF-1 induced up to 25% of cells in culture to extend processes > 75
      microns in length by 6 d; AF-2 had a lesser but highly significant effect. To
      verify that neurite outgrowth was from retinal ganglion cells per se, we applied
      the lipophilic dye 4-Di-10-ASP to the optic tectum and allowed it to diffuse up
      the optic nerve for several days before culturing the retina. A far greater
      percentage of cells containing the dye showed axonal outgrowth than was observed
      from the overall cell population, indicating that ganglion cells are selective
      targets of the factors. The effects of AF-1 or AF-2 were not secondary to
      enhanced viability, since neither overall cell survival nor the number of retinal
      ganglion cells remaining in culture after 6 d was affected by the presence of the
      factors. The activity of AF-1 and AF-2 was not mimicked by several defined
      factors tested over a broad concentration range, for example, NGF, BDNF, NT-3,
      CNTF, taurine, retinoic acid, acidic or basic fibroblast growth factors. The
      concentration of AF-1 is considerably higher in CM than in optic nerve
      homogenates, suggesting that it is actively secreted; AF-2 has a similar
      concentration intra- and extracellularly. Insofar as AF-1 and AF-2 derive from
      cells of the optic nerve and act upon retinal ganglion cells, they are likely to
      be important in inducing optic nerve regeneration in vivo.

PMID- 7643199
TI  - Adrenergic calcium signaling in astrocyte networks within the hippocampal slice.
AB  - Norepinephrine (NE) and glutamate (Glu) initiate intracellular calcium ([Ca2+]i)
      transients, oscillations, and intracellular [Ca2+]i waves in cultured astrocytes.
      To further elucidate the significance of NE- and Glu-evoked astrocytic [Ca2+]i
      signaling to neuron-astrocyte communication in the mature CNS, [Ca2+]i of
      astrocyte networks within hippocampal slices (P21-42) was measured during bath
      application of NE and Glu receptor agonists. Astrocytes in stratum radiatum were
      identified by highly negative membrane potentials (75 +/- 3 mV), absence of
      action potentials, and dye coupling following intracellular injection of the
      [Ca2+]-sensitive dye calcium orange. NE (2-100 microM) evoked [Ca2+]i increases
      (7 of 8 slices, 24 of 24 cells in responding slices) characterized by an initial
      rise, 20-50 sec to peak, followed by a slower return to baseline (over
      approximately 8 min). The alpha 1-agonist phenylephrine (PE) (10-100 microM)
      evoked complex [Ca2+]i signals (22 of 26 slices, 90 of 90 cells in responding
      slices) composed of both a prolonged component (5.1 +/- 1.8 min), synchronized in
      neighboring cells, and multiple, mainly asynchronous [Ca2+]i spikes (25.0 +/-
      11.6 sec). PE responses were completely blocked by the alpha 1-antagonist
      prazosin (200 nM, n = 4 slices), but not by the alpha 2-antagonist yohimbine (n =
      3 slices). The alpha 2-agonist clonidine (10-100 microM) did not increase [Ca2+]i
      (n = 4 slices). alpha 1-mediated [Ca2+]i transients were observed after removal
      of extracellular [Ca2+]o (n = 8 of 9 slices), indicating PE-induced Ca2+ release
      from intracellular stores. Adrenergic responses were mediated by alpha 1
      receptors localized to astrocytes because PE and NE increased [Ca2+]i of acutely
      isolated hippocampal astrocytes. Glu (0.75-2.0 mM) did not increase astrocytic
      [Ca2+]i in slices (0 of 7), even in the presence of the Glu uptake inhibitor L
      trans-pyrrollidine-2,4-dicarboxylic acid (PDC) (0 of 5 slices), or in acutely
      isolated astrocytes (0 of 7 cells). The metabotropic agonist t-ACPD (30 or 50
      microM) did not increase astrocytic [Ca2+]i in hippocampal slices (0 of 5), while
      kainate (200 microM or 1 mM) induced brief (1-2 min) [Ca2+]i increases only
      rarely (2 of 8 applications in 6 slices). These results support a primary role of
      NE release and alpha 1-adrenoceptor stimulation in neuron-astrocyte communication
      in the mature CNS.

PMID- 7643200
TI  - The leech homeobox gene Lox4 may determine segmental differentiation of
      identified neurons.
AB  - We cloned and characterized a new leech homeobox gene, Lox4, a homolog of the
      Drosophila genes Ultrabithorax and abdominal-A. Lox4 has a complex and dynamic
      pattern of expression within a series of segmentally homologous neurons. These
      include a pair of specialized motor neurons of one segmental ganglion, the
      rostral penile evertors (RPEs), and their segmental homologs in other midbody
      ganglia. During gangliogenesis, Lox4 was expressed within this series of neurons
      in three different temporal patterns: (1) it was never expressed in the RPE
      homologs of ganglia 1-3; (2) it was expressed in the RPEs during gangliogenesis,
      but was turned off when these neurons started to differentiate after
      gangliogenesis; and (3) it was expressed in the RPE homologs of segments 4-5 and
      7-21 during gangliogenesis and the subsequent period of axonogenesis. We found
      that these neurons have three distinct peripheral axonal morphologies that
      correlate with the three temporal patterns of expression. Our results suggest
      that the homeobox gene Lox4 may determine neuronal identities within this series
      of segmental homologs.

PMID- 7643201
TI  - Repeated confocal imaging of individual dendritic spines in the living
      hippocampal slice: evidence for changes in length and orientation associated with
      chemically induced LTP.
AB  - Using confocal microscopy in conjunction with microdrop application of Dil, we
      have imaged and measured individual dendritic spines of living hippocampal CA1
      pyramidal neurons in acute brain slices, before and approximately 3 hr after
      induction of long-term potentiation by chemical means. Statistical analysis of
      changes in the length of individual spines, and comparison with results of Monte
      Carlo simulations, suggests that two forms of structural change occur in
      chemically induced long-term potentiation: growth of a subpopulation of small
      spines, and angular displacement of spines. These changes could provide a
      structural basis for the expression of long-term potentiation.

PMID- 7643202
TI  - The D2 antagonist spiperone mimics the effects of olfactory deprivation on
      mitral/tufted cell odor response patterns.
AB  - Wistar rats had a single nare occluded on postnatal day 30, depriving the
      ipsilateral olfactory bulb of odor stimulation. The deprivation lasted for either
      1-2 months (short-term) or 12 months (long-term). As previously reported,
      deprivation greatly reduced tyrosine hydroxylase immunoreactivity (the rate
      limiting enzyme for dopamine synthesis) in the glomerular layer of the
      ipsilateral olfactory bulb. The nare was then reopened and odor response patterns
      of mitral/tufted cells were examined. The proportion of mitral/tufted cell single
      units responding to a single odor was enhanced by deprivation. Furthermore, the
      proportion of mitral/tufted cells responding to more than one odor was increased
      by deprivation, suggesting a decrease in discrimination. Finally, in undeprived
      bulbs, the dopamine D2 receptor antagonist spiperone mimicked the effects of
      deprivation on mitral/tufted cell odor response patterns. The results are
      interpreted as an activity-dependent dopamine modulation of lateral and feedback
      inhibition in the olfactory bulb, and are compared with similar events in the
      dark-adapted retina.

PMID- 7643203
TI  - Tactile resolution: peripheral neural mechanisms underlying the human capacity to
      determine positions of objects contacting the fingerpad.
AB  - We measured the ability of humans to discriminate the positions of spherical
      objects passively contacting the fingerpad. The discrimination threshold averaged
      0.55 mm for a moderately curved sphere (radius 5.80 mm) and decreased to 0.38 mm
      for a more curved sphere (radius 1.92 mm); since the receptor density is about 1
      per mm2, these values are substantially smaller than those predicted by the
      sampling theorem (referred to as hyperacuity). To elucidate the underlying neural
      mechanisms, responses to the same spheres and random sequences of stimuli were
      recorded from single Merkel afferents (SAIs) and Meissner afferents (RAs) in
      anesthetized monkeys. For multiple applications of identical stimuli,
      coefficients of variation of responses were around 3%. Profiles of responses
      across the SAI population were "hill-shaped." A change in position of the
      stimulus on the skin resulted in a matching shift of the profile, evident over
      the whole profile for the more curved sphere but ony at the skirts for the less
      curved sphere. The shift in response profiles, relative to the standard
      deviations, increased as the change in position increased, and was more reliable
      for the more curved sphere. Responses were measured over four time frames: 0.2,
      0.3, 0.5, and 1.0 sec. Although responses increased with an increase in
      integration time, so, too, did their standard deviations, so that signal-to-noise
      ratios or the resolution in the SAI population was bout the same at 0.2 sec as at
      1.0 sec. Only half the RAs responded; responses were small, but signalled
      reliable information about the position of the stimulus.

PMID- 7643204
TI  - Visual motion detection circuits in flies: peripheral motion computation by
      identified small-field retinotopic neurons.
AB  - Giant motion-sensitive tangential neurons in the lobula plate are thought to be
      cardinal elements in the oculomotor pathways of flies. However, these large
      neurons do not themselves compute motion, and elementary motion detectors have
      been proposed only from theory. Here we identify the forms, projections, and
      responses of small-field retinotopic neurons that comprise a well known pathway
      from the retina to the lobula plate. Already at the level of the second and third
      synapses beneath the photoreceptor layer, certain of these small elements show
      responses that distinguish motion from flicker. At a level equivalent to the
      vertebrate inner plexiform layer (the fly's outer medulla) at least one
      retinotopic element is directionally selective. At the inner medulla, small
      retinotopic neurons with bushy dendrites extending through a few neighboring
      columns leave the inner medulla and supply inputs onto lobula plate tangentials.
      These medulla relays have directionally selective responses that are
      indistinguishable from those of large-field tangentials except for their
      amplitude and modulation with contrast frequency. Centrifugal neurons leading
      back from the inner medulla out to the lamina also show orientation-selective
      responses to motion. The results suggest that specific cell types between the
      lamina and inner medulla correspond to stages of the Hassenstein-Reichardt
      correlation model of motion detection.

PMID- 7643205
TI  - Neuropeptides phase shift the mammalian circadian pacemaker.
AB  - We studied the influence on circadian rhythms of peptides that have been reported
      to be colocalized in suprachiasmatic nucleus (SCN) neurons. Gastrin-releasing
      peptide (GRP1-27), peptide histidine isoleucine (PHI), and vasoactive intestinal
      polypeptide (VIP) were microinjected into the suprachiasmatic nucleus (SCN)
      region of Syrian hamsters free running under three different constant lighting
      conditions. All peptide injections caused phase-dependent phase shifts of hamster
      locomotor activity rhythms which were unaffected by constant lighting conditions.
      GRP1-27 (150 pmol) caused large phase delays when injected at circadian times
      (CT) 12-16, modest phase advances when administered at CT20-24, and few shifts
      during the subjective day. Injections of saline vehicle at any of these phases
      caused only very small phase shifts. Phase delays induced by GRP1-27 at CT12-14
      were dose dependent, unrelated to injection volume (at a constant dose), and
      attenuated by pretreatment with the BN/GRP-preferring receptor antagonist BIM
      26226. VIP (150 pmol) caused moderate phase delays at CT12-14 and moderate phase
      advances at CT20-24. PHI (150 pmol) caused moderate phase delays at CT12-14 only.
      Coadministration of 150 pmol of GRP1-27, PHI, and VIP in an equimolar
      neuropeptide cocktail (50 pmol of each peptide) caused phase delays at CT12-14
      and phase advances at CT20-24 which did not differ from those induced by 150 pmol
      of GRP1-27 alone at these phases. The shifts induced by 150 pmol of the peptide
      cocktail were smaller than the sum of the shifts induced by 50 pmol doses of each
      peptide administered separately at those phases. Since the phase-delaying effects
      of the cocktail were weaker than the summed effects of the component 50 pmol
      doses of the peptides, these data demonstrate a lack of synergism among the
      effects of these peptides. Since GRP1-27 (150 pmol) evoked shifts similar in
      magnitude to those of the cocktail, there is no evidence that these apparently
      colocalized neuropeptides must interact to exert maximal effects on the circadian
      pacemaker.

PMID- 7643206
TI  - Proprioceptive sensory neurons of a locust leg receive rhythmic presynpatic
      inhibition during walking.
AB  - Mechanosensory neurons from a proprioceptor (the femoral chordotonal organ)
      signal the movements and positions of the femorotibial joint of a locust leg.
      Intracellular recordings from these neurons during walking show that their spikes
      are superimposed on a depolarizing synaptic input generated near their output
      terminals in the CNS. The depolarization consists of a rhythmic synaptic input at
      each step, and a sustained input that begins before walking commences. In
      different sensory neurons, which signal particular features of the movement, the
      rhythmic depolarization occurs at distinct times during either the swing or
      stance phases of the step cycle. The depolarizing input is timed to coincide with
      the greatest spike response of a sensory neuron. The input is associated with a
      conductance change, appears to reverse just above resting potential, and thus has
      similar properties to the presynaptic inhibition in these same neurons during
      imposed joint movements (Burrows and Laurent, 1993; Burrows and Matheson, 1994).
      Three sources could contribute to these inputs: (1) interactions between sensory
      neurons of the same receptor signaling the same movement, (2) signals from
      different receptors in the same leg and other legs, and (3) outputs of central
      neurons involved in generating walking. When the leg, whose movements the sensory
      neurons signal is removed, both the sustained and rhythmic synaptic inputs
      persist. Sensory neurons in isolated ganglia treated with pilocarpine are also
      depolarized in phase with a rhythmic pattern expressed in leg motor neurons,
      indicating that central neurons must contribute. The maintained synaptic input to
      the terminals means that the overall effectiveness of the sensory spikes in
      evoking EPSPs in postsynaptic neurons will be reduced during walking, and the
      rhythmic component means that the spikes from particular sensory neurons will be
      further reduced at particular phases of the step cycle that they signal best.

PMID- 7643207
TI  - Transient memory impairment in monkeys with bilateral lesions of the entorhinal
      cortex.
AB  - Performance on five behavioral tasks was assessed post-operatively in Macaca
      fascicularis monkeys prepared with bilateral lesions of the entorhinal cortex (E
      group). Three of the tasks were also readministered 9-14 months after surgery.
      Initial learning of the delayed nonmatching-to-sample (DNMS) task was impaired in
      the E animals relative to unoperated control monkeys. On the delay portion of
      DNMS, the performance of E animals was nearly at control levels at short delays
      (up to 60 sec) but was impaired at 10 min and 40 min retention intervals. On the
      retest of DNMS, the E animals performed normally at all retention intervals. The
      E animals were unimpaired on the four other memory tasks. Neuroanatomical studies
      revealed a significant transverse expansion of the terminal field of the
      perirhinal cortical projection in the CA1 region of the hippocampus. Compared to
      unlesioned, anatomical control monkeys, the transverse length of the perirhinal
      terminal field in CA1 increased approximately 70% in the E monkeys. Although this
      was a striking morphological alteration, it is not known whether the sprouting of
      this projection influenced the behavioral recovery. The results of these studies
      suggest that the entorhinal cortex may normally participate in the learning and
      performance of tasks that are dependent on the medial temporal lobe memory
      system. However, recovery of normal DNMS performance demonstrates that the
      entorhinal cortex is not, by itself, essential for learning and performance of
      such tasks.

PMID- 7643208
TI  - Ligand-induced growth cone collapse: amplification and blockade by variant GAP-43
      peptides.
AB  - Growth cones are powerful amplifiers for signals from the microenvironment. Their
      collapse can be triggered by cell surface components of myelin and brain
      membranes, as well as by soluble ligands, including neurotransmitters. GAP-43 is
      a protein concentrated on the inner surface of the growth cone membrane. Assayed
      in isolation, it interacts with the heterotrimeric protein, G(o), and in oocytes
      it amplifies the effects of ligand-triggered G protein activation. We wished to
      examine whether GAP-43 serves to amplify signals at the growth cone. The G(o)
      stimulating region of GAP-43 is encoded in the 10 amino acids (MLCCMRRT-KQ) of
      the first exon. We examined the effect of this peptide upon chick dorsal root
      ganglion growth cone collapse and neurite retraction triggered by brain membranes
      or myelin, as well as by serotonin. We find that application of the GAP-43 1-10
      peptide amplifies the effects of all three ligands. The amplification is greater
      when GAP-43 1-10 is injected intracellularly. Peptides with amino acid
      substitutions for the two cysteine residues manifest parallel changes in growth
      cone collapse and G(o) stimulation. In particular, tyrosine or methionine
      substitutions cause the peptide to inhibit G(o) and to block induced growth cone
      collapse. The GAP-43 peptides therefore regulate the sensitivity of growth cones
      to extrinsic signals. The modified peptides serve as a starting point for the
      design of reagents to enhance CNS regeneration.

PMID- 7643209
TI  - CNS-derived neural progenitor cells for gene transfer of nerve growth factor to
      the adult rat brain: complete rescue of axotomized cholinergic neurons after
      transplantation into the septum.
AB  - A CNS-derived conditionally immortalized temperature-sensitive neural progenitor
      (CINP) cell line was used to generate NGF-secreting cells suitable for
      intracerebral transplantation. The cells were transduced by repeated retroviral
      infection, using a vector containing the mouse NGF cDNA under the control of the
      LTR promoter. Subcloning at the permissive temperature (33 degrees C) identified
      a highly NGF-secreting clone (NGF-CINP), which contained multiple copies of the
      transgene and released NGF at a rate of 2 ng/hr/10(5) cells in vitro, both at 33
      and 37 degrees C, which was approximately 1 order of magnitude higher than what
      was possible to achieve in the heterogeneously infected cell cultures. After
      transplantation to the brain, the NGF-CINPs differentiated into cells with a
      predominant glia-like morphology and migrated for a distance of 1-1.5 mm from the
      implantation site into the surrounding host tissue, without any signs of
      overgrowth and tumor formation. Grafts of NGF-CINP cells implanted into the
      septum of adult rats with complete fimbria-fornix lesion blocked over 90% of the
      cholinergic cell loss in the medial septum and grafts placed in the intact
      striatum induced accumulation of low-affinity NGF receptor positive fibers around
      the implantation site. Expression of the NGF transgene in vivo was demonstrated
      by RT-PCR at 2 weeks after grafting. It is concluded that the immortalized neural
      progenitors have a number of advantageous properties that make them highly useful
      experimental tools for gene transfer to the adult CNS.

PMID- 7643210
TI  - Temperature compensation and temperature entrainment of the chick pineal cell
      circadian clock.
AB  - We have used an in vitro model system of the circadian clock, dispersed chick
      pineal cells, to examine the effects of temperature on the circadian clock of a
      homeotherm. This preparation enabled us to isolate a circadian clock from in vivo
      homeostatic temperature regulation and expose cells to both constant temperatures
      and abrupt temperature changes. By manipulating the temperature of the pineal
      cells, we have demonstrated that (1) the circadian clock compensates its period
      for temperature changes over the range of 34-40 degrees C; Q10 = 0.83, a value
      within the range of Q10 values measured for poikilothermic circadian clocks; (2)
      temperature pulses (42 degrees C, 6 hr duration) shift the phase (advance and
      delay) of the circadian rhythm in a phase-dependent manner; and (3) a temperature
      cycle (18 hr at 37 degrees C, 6 hr at 42 degrees C) will entrain the circadian
      clock in vitro. This is the first demonstration of temperature entrainment of the
      circadian clock of a homeotherm in vitro. In addition we have found that
      temperature directly influences the synthesis and release of melatonin, the
      primary hormonal product of the pineal gland. The biosynthesis of melatonin is
      strongly temperature dependent with a Q10 > 11 when melatonin release is measured
      at ambient temperatures between 31 degrees C and 40 degrees C. In contrast, 6 hr
      42 degrees C temperatures pulses acutely inhibit melatonin release in a manner
      similar to that seen previously with light pulses. These results demonstrate that
      a circadian clock from a homeothermic vertebrate is temperature compensated, yet
      temperature cycles can entrain the circadian melatonin rhythm. Thus, the chick
      pineal circadian oscillator has retained all the fundamental properties of
      circadian rhythms.

PMID- 7643211
TI  - Pre- and postsynaptic determinants of EPSC waveform at cerebellar climbing fiber
      and parallel fiber to Purkinje cell synapses.
AB  - Excitatory postsynaptic currents (EPSCs) at the parallel fiber and climbing fiber
      to Purkinje cell synapses were studied by whole-cell clamping Purkinje cells in
      cerebellar slices. Reducing glutamate release with adenosine or GABA decreased
      the amplitude of the EPSCs, with a larger suppression being produced at the
      parallel fiber synapse. Reducing glutamate release also speeded the decay of the
      EPSCs, and this effect was not a series resistance artefact since postsynaptic
      reduction of the current with CNQX did not speed the EPSC decay. Blocking
      glutamate uptake slowed the decay of the EPSCs. At the climbing fiber synapse,
      adenosine had little suppressive effect on the smaller EPSC evoked by the second
      of a pair of stimuli. Blocking desensitization of postsynaptic AMPA receptors
      prolonged the EPSC decay, preferentially increased the size of the second EPSC,
      and resulted in adenosine having a similar suppressive effect on the first and
      second EPSC. These data suggest that, at these synapses, the fall of glutamate
      concentration in the synaptic cleft overlaps with the decay of the EPSC, and that
      the EPSC size and duration are controlled by the amount of glutamate released,
      the rate of glutamate uptake, and desensitization.

PMID- 7643212
TI  - Functional differentiation of adult neural circuits from a single embryonic
      network.
AB  - The stomatogastric nervous system (STNS) of adult lobsters and crabs generates a
      number of different rhythmic motor patterns which control different regional
      movements of the foregut. Since these output patterns are generated by discrete
      neural networks that, in the adult, are well characterized in terms of synaptic
      and cellular properties, this system constitutes an ideal model for exploring the
      mechanisms underlying the ontogeny of neural network organization. The foregut
      and its rhythmic motor patterns were studied in in vitro STNS nerve-muscle
      preparations of the embryo and different larval stages of the lobster Homarus
      gammarus. The development of Homarus comprises a long embryonic stage in ovo
      followed by three pelagic larval stages prior to the onset of benthic life.
      During these stages the foregut itself develops slowly from a simple ectodermal
      invagination that occurs in the embryo. During successive larval stages it
      progressively acquires all the specialized structures and shape of the adult
      foregut. In contrast, the STNS is morphologically recognizable at early embryonic
      stages. In all recorded stages the STNS spontaneously expresses rhythmic motor
      activity. During development, this activity is progressively restructured,
      beginning with a single rhythmic motor pattern in the embryo where all the
      stomodeal muscles are strongly coordinated. In subsequent stages, however, this
      single pattern is progressively subdivided to give rise eventually to the three
      discrete rhythmic motor patterns characteristic of the adult STNS. Our data
      suggest that rather than a dismantling of redundant embryonic and larval neural
      networks, the different adult networks emerge as a progressive partitioning of
      discrete circuits from a single embryonic network.

PMID- 7643213
TI  - Toxin-insensitive Ca current in dorsal raphe neurons.
AB  - About 54% of the whole-cell Ca current recorded in dorsal raphe neurons cannot be
      categorized as N-, L-, or P-type Ca current. This current, ICa-Raphe, was not
      blocked by a combination of nimodipine, omega-CgTx-GVIA, and omega-AGA-IVA.
      Differences in toxin sensitivity and voltage dependence suggest that ICa-Raphe is
      distinct from Q- or R-type Ca currents. In raphe neurons activation of 5-HT1A
      receptors by 5-HT inhibits approximately 50% of the Ca current and slows
      activation. 5-HT inhibits both N-type Ca channels and ICa-Raphe channels by
      approximately 50% and slows the activation of both currents to a similar extent.
      Other similarities between ICa-Raphe and N-type Ca current were observed; they
      are both blocked to a similar extent by Ni2+, their activation properties, their
      current kinetics and channel availability as a function of holding potential are
      almost identical. Thus, ICa-Raphe represents a current that is not sensitive to
      known antagonists, but which is similar to N-type Ca current. Although it is
      possible that ICa-Raphe belongs to a heretofore undiscovered family of Ca
      channels it is also possible that it represents an omega-CgTx GVIA-insensitive
      isoform of the N-type Ca channel family.

PMID- 7643214
TI  - Expression of mef2 genes in the mouse central nervous system suggests a role in
      neuronal maturation.
AB  - Members of the myocyte enhancer factor 2 (MEF2) gene family are expressed in a
      dynamic pattern during development of the CNS of pre- and postnatal mice. The
      four MEF2 genes, Mef2A, -B, -C, -D, encode transcription factors belonging to the
      MADS (MCM1-agamous-deficiens-serum response factor) superfamily of DNA binding
      proteins. MEF2 factors have previously been shown to be positive regulators of
      gene expression in terminally differentiated muscle cells. To begin to determine
      the role of MEF2 factors in CNS development, we used in situ hybridization with
      gene-specific cRNA probes to define the expression patterns of each of the four
      Mef2 mRNAs in the developing and mature mouse CNS. Mef2C mRNA was first detected
      in a ventral portion of the telencephalon at 11.5 d postcoitum (p.c.). By 13.5 d
      p.c., each of the four Mef2 genes were expressed in overlapping yet distinct
      patterns in regions of the frontal cortex, midbrain, thalamus, hippocampus, and
      hindbrain. Temporal and spatial patterns of embryonic Mef2 gene expression
      appeared to follow gradients of neuron maturation and suggested that the onset of
      Mef2 gene expression coincides with withdrawal from the cell cycle and initiation
      of neuronal differentiation. This correlation is particularly striking for
      Purkinje cells in the cerebellum. Since the molecular mechanisms that regulate
      neuron differentiation are unknown, we propose that the MEF2 factors are likely
      to play an important role in this process.

PMID- 7643215
TI  - Postnatal development of synchronized network oscillations in the ferret dorsal
      lateral geniculate and perigeniculate nuclei.
AB  - Extracellular and intracellular recordings from slices of ferret dorsal lateral
      geniculate nucleus (LGNd) at postnatal ages P10-53 were performed to examine the
      postnatal development of spindle waves and the ability of block of GABAA
      receptors to alter these spindle waves into a slower, synchronous oscillation. As
      in prior studies in the adult, intracellular and extracellular recordings at ages
      P33-53 revealed robust spindle waves to be present in both the LGNd and
      perigeniculate nucleus (PGN). Intracellular recordings from thalamocortical relay
      cells in the A-laminae of the LGNd revealed that these cells received repetitive
      inhibitory postsynaptic potentials (IPSPs) at 6-9 Hz during the generation of
      spindle waves, and generated rebound low threshold Ca2+ spikes and bursts of 2-6
      action potentials following each second or third IPSP. Intracellular recordings
      from the GABAergic neurons of the PGN at P33-53 revealed barrages of EPSPs that
      activated low threshold Ca2+ spikes and high frequency burst discharges of 2-10
      action potentials during spindle wave generation. In contrast, full spindle waves
      were absent at ages prior to approximately P22 and spindle waves between the ages
      of P26 and approximately P30 were relatively weak and associated with only one or
      two action potentials per burst in both PGN neurons and LGNd relay cells. Bath
      application of the GABAA antagonist bicuculline methiodide at P41-53 resulted in
      a conversion of normal spindle waves into a marked 2-4 Hz oscillation in which
      the action potential firing of both thalamocortical relay and PGN neurons was
      greatly increased. In contrast, block of GABAA receptors prior to age P39 did not
      result in the generation of the slowed, 2-4 Hz network oscillation. Investigation
      of the electrophysiological properties of PGN neurons revealed that the postnatal
      development of spindle waves and bicuculline-induced slow oscillations were
      associated with an increase in the ability of PGN neurons to generate high
      frequency bursts of action potentials, suggesting that these changes in
      electrophysiological properties may contribute to the late development of
      synchronized oscillations in the ferret LGNd.

PMID- 7643216
TI  - Characterization of a rat gene, rMAL, encoding a protein with four hydrophobic
      domains in central and peripheral myelin.
AB  - Wrapping and compaction of myelin sheaths around axons require specific membrane
      and membrane-associated proteins. Transmembrane proteins like proteolipid protein
      (PLP), the peripheral myelin protein 22 (PMP-22) and P0 as well as myelin basic
      protein (MBP) are crucial for this process. We have isolated a rat cDNA,
      initially denominated NS 3, that is mainly expressed in the myelinating cells of
      the nervous system, the oligodendrocytes and Schwann cells. The cDNA encodes a
      highly hydrophobic protein of 16.8 kDa with four putative transmembrane domains.
      The putative NS 3 protein lacks a N-terminal hydrophobic leader sequence and has
      no consensus sequence for N-linked glycosylation. In contrast to PLP and PMP-22,
      the first and third putative transmembrane domain of the NS 3 protein contain
      charged amino acids, a feature which resembles the structure of gap junction
      proteins. Sequence analysis showed that NS 3 is the rat homolog of a human gene
      called MAL that was cloned from, and is expressed in various T-cell lines.
      Therefore, we call this gene rMAL (rat MAL). In the nervous system, the
      expression of rMAL, mRNA begins after birth and is highest during myelination. In
      situ hybridization shows that rMAL mRNA is exclusively expressed in white and
      gray matter oligodendrocytes in the CNS and in myelinating Schwann cells in
      peripheral nerves. Immunohistochemistry using a peptide-specific antibody
      localized the rMAL protein in the myelinated areas of the CNS and PNS.
      Furthermore, we demonstrate by immunoblot analysis that rMAL is a component of
      myelin. Its structure and distribution suggest that the rMAL protein might play
      an important role in compact myelin. We propose that the name rMAL protein refers
      to rat Myelin And Lymphocyte protein.

PMID- 7643217
TI  - BDNF enhances the differentiation but not the survival of CNS stem cell-derived
      neuronal precursors.
AB  - We have previously reported the isolation of an EGF-responsive precursor from the
      embryonic and adult mouse striatum. This precursor exhibits self renewal and the
      ability to produce a sphere of undifferentiated cells which can be induced to
      differentiate into neurons and glia. RT-PCR analysis of these spheres of
      undifferentiated cells revealed the expression of mRNA for the trkB neurotrophin
      receptor, both with and without the catalytic domain, and little or no expression
      of trkA or trkC. We examined the actions of BDNF on the fate of EGF-generated
      neural precursors. Ten days after a one-time exposure to BDNF, single EGF
      generated spheres showed a twofold increase in neuron number and a marked
      enhancement in neurite outgrowth. Examination of neuronal nuclei with
      immunochemical probes for c-fos and bromodeoxyuridine revealed that the actions
      of BDNF were directly upon neuronal cells and did not involve division of
      neuronal precursors. The twofold increase in neuronal number due to BDNF,
      observed after 10 d in vitro, was significantly reduced after 21 d in vitro and
      was not apparent at 27 d in vitro. Quantitative analyses revealed that while
      repeated application of BDNF did not prevent the loss of neuron number over time,
      it did result in a significant increase in neurite numbers. Moreover, delayed
      addition of BDNF mimicked the increase in neuronal numbers seen when BDNF was
      present throughout. These BDNF actions did not appear to involve the enhancement
      of a novel neuronal phenotype, with all effects being due to increase in the
      numbers and neurite outgrowth of neurons that colocalize GABA and substance P.
      These findings suggest that BDNF markedly enhances the antigenic and morphologic
      differentiation of EGF-generated neuronal precursors. BDNF alone does not appear
      to act as a survival factor for neuronal precursors nor is it sufficient for
      preventing their death over time.

PMID- 7643218
TI  - Rats with fimbria-fornix lesions display a place response in a swimming pool: a
      dissociation between getting there and knowing where.
AB  - Some theories of hippocampal formation function postulate that it is involved in
      using the relationships between distal cues for spatial navigation. That rats
      with damage to the hippocampal formation are impaired in learning place responses
      of escaping to a platform hidden just below the surface of the water of a
      swimming pool, supports this view. Using rats with fimbria-fornix (FF) lesions,
      we examined whether their impairment is related to an inability to learn how to
      reach the platform as opposed to learning its location. In a first experiment,
      the FF rats were impaired in learning to swim to a hidden platform but could swim
      to a visible platform. In a second experiment, after being pretrained to swim to
      a visible platform, the FF rats swam to, paused, and searched the vicinity of the
      platform's previous location when it was removed. This finding showed that the FF
      rats expected to find the platform at that location. Additional tests confirmed
      that they had learned a place response. Despite having acquired a place response,
      they still could not acquire new place responses when only the hidden platform
      training procedure was used. Thus, these results in dissociating the processes of
      "getting there" and "knowing where" suggest that the FF rats' impairment may be
      in some process of motoric control, such as path integration, rather than in
      learning the location of the platform in relation to ambient cues. The results
      are discussed in relation to relevant theories of hippocampal function.

PMID- 7643219
TI  - Regional expression and cellular localization of the Na(+)-dependent inorganic
      phosphate cotransporter of rat brain.
AB  - We have recently isolated and identified a brain specific Na(+)-dependent
      inorganic phosphate (Pi) cotransporter cDNA (rBNPI) from a rat brain cDNA library
      (Ni, et al., 1994). We now report the regional and developmental expression, as
      well as the cellular localization, of rBNPI mRNA in the rat brain. In situ
      hybridization histochemistry reveals that rBNPI mRNA is selectively expressed in
      neuron-enriched regions of the adult rat brain, such as the cerebral cortex,
      hippocampus, and cerebellum. Cellular localization of rBNPI transcripts reveals
      expression in both pyramidal and granule neurons in these regions. By contrast,
      little to no hybridization signal was observed in white matter-enriched areas
      such as the corpus callosum. The expression of rBNPI mRNA was determined during
      pre- and postnatal development of the rat CNS. From embryonic day 17 to early
      postnatal day 10 (PND 10), there is a rather widespread but diffuse pattern of
      rBNPI expression in brain. During late postnatal development, however, the
      expression of rBNPI mRNA becomes confined to discrete populations of neurons in
      the cerebral cortex, hippocampus, and cerebellum. Thus, rBNPI expression is
      developmentally regulated and abundant levels of mRNA are found in rather
      discrete populations of neurons in the adult rat brain. The latter suggests that
      rBNPI may serve to selectively regulate intracellular Pi transport in certain
      neurons for either metabolic and (or) signaling events.

PMID- 7643220
TI  - Cloning of rat interleukin-3 receptor beta-subunit from cultured microglia and
      its mRNA expression in vivo.
AB  - The high-affinity receptors for interleukin-3 (IL-3), GM-CSF, and IL-5 are
      composed of a ligand binding (alpha-) and a transducing (beta-) subunit. Two
      distinct transducing subunits (clones AIC2A and AIC2B) have been cloned from
      mouse, whereas in humans, only one (common) beta-subunit (beta c) has been found.
      A PCR-based cloning strategy was used to obtain a full-length cDNA sequence from
      rat microglia including 5'-untranslated regions. Sequence analysis revealed a
      number of features indicative of the presence of only one beta-subunit in the
      rat. Most likely, the new rIL-3R beta cDNA is the rat equivalent of human
      respective murine (AIC2B) beta c subunits. Regulation of rIL-3R beta mRNA
      expression was investigated in cultured microglia and in vivo. Purified microglia
      expressed significant amounts of rIL-3R beta mRNA. Addition of lipopolysaccharide
      (LPS) resulted in a marked upregulation of rIL-3R beta mRNA within approximately
      4 hr. No downregulation was observed within 1 week's treatment. No rIL-3R beta
      mRNA was detectable in normal rat brain. However, 3 hr after a single injection
      of LPS into the tail vein of a rat, a marked induction of receptor mRNA occurred
      in a variety of brain regions. Transcriptional rates subsided significantly after
      24 hr. rIL-3R beta mRNA was visualized by in situ hybridizations with cRNA
      antisense probes in ramified cells formerly characterized as microglial cells.
      rIL-3R beta mRNA was also induced in rat brain after occlusion of middle cerebral
      artery (MCAO).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7643221
TI  - Seizures and failures in the giant fiber pathway of Drosophila bang-sensitive
      paralytic mutants.
AB  - Drosophila bang-sensitive paralytic mutants suffer from hyperactivity and
      paralysis following a mechanical shock; after recovery from paralysis, they
      cannot be paralyzed for a refractory period lasting up to 1 hr. Previously, we
      have shown that in easily shocked (eas), a typical bang-sensitive mutant,
      electrical shocks delivered to the brain cause seizure-like activity in the
      dorsal longitudinal flight motor neurons (DLMmns), and failure of giant fiber
      (GF) stimulation to evoke DLM potentials via the escape response pathway
      (Pavlidis et al., 1994). Here, we show that seizure and failure in the GF pathway
      with a refractory period is common to all six members of the bang-sensitive
      class. This syndrome was not found in any of eight other excitability mutants,
      including those affecting voltage-gated sodium or potassium-channel function. We
      show that failure occurs at the synapse between a peripherally synapsing
      interneuron (PSI) and the DLMmns, while the DLMmn-DLM neuromuscular junctions
      remain functional. Additionally, failure occurs in all other GF pathway-activated
      muscles. Failures occurred without seizures in the tergotrochanteral jump muscle
      (TTM), as was also found in approximately 10% of DLM tests, suggesting that
      seizures and failures may be independent events. This hypothesis is supported by
      the finding that, in double mutant combination with mlenapts, which suppresses
      behavioral bang sensitivity, DLM failures, but not seizures, were reduced.

PMID- 7643222
TI  - Long-term potentiation disrupts auditory gating in the rat hippocampus.
AB  - The consequence of long-term potentiation (LTP) of hippocampal commissural inputs
      was investigated in an auditory gating paradigm. Auditory evoked potentials
      (AEPs) were recorded in the CA3b region of the hippocampus of rats anesthesitized
      with chloral hydrate. Two tones were delivered 0.5 sec apart; in this paradigm,
      the second AEP is diminished compared to the first. Electrical stimulation was
      applied to hippocampal commissural fibers to generate field potentials and
      population spikes which were recorded at the same site as the AEPs. LTP of the
      commissural input (initiated by three trains of 250 Hz/1 sec stimulation) was
      associated with changes in the AEPs: on average, the response to the first tone
      decreased and the response to the second tone increased, resulting in the
      disruption of auditory gating. When high-frequency stimulation of the commissural
      input failed to result in LTP, no effect on the AEPs was seen. If 3-(2
      carboxypiperazin-4-yl)-propyl-L-phosphonic acid (CPP; 6 mg/kg, i.p.), an
      antagonist to the NMDA subclass of glutamate receptors, was administered prior to
      high-frequency stimulation, LTP induction was blocked and AEPs were not affected.
      Finally, reversal of LTP, achieved by high-frequency stimulation of CA3 input
      that was heterosynaptic to the particular commissural fibers at which the LTP was
      originally generated, caused disrupted auditory gating to return to normal. A
      model of reciprocal LTP and heterosynaptic depression of commissural and auditory
      input pathways is proposed to explain these findings.

PMID- 7643223
TI  - Neuroligand-evoked calcium-dependent release of excitatory amino acids from
      Schwann cells.
AB  - Bradykinin caused a receptor-mediated increase in release of the excitatory amino
      acids (EAAs) glutamate and aspartate from Schwann cell cultures obtained from
      dorsal root ganglia (DRG) together with an increase in the cytoplasmic level of
      free calcium. Perturbations which inhibited brady-kinin-induced calcium
      mobilization prevented the release of EAAs from glia. The addition of ionomycin
      caused a calcium-dependent release of EAAs. Therefore, bradykinin causes calcium
      dependent-release of EAAs from DRG Schwann cells. Bradykinin did not cause cell
      swelling and p-chloromercuriphenylsulfonic acid, an inhibitor of the electrogenic
      glutamate transporter, did not reduce bradykinin-induced EAA release. Therefore,
      bradykinin stimulates EAA release from Schwann cells through a mechanism that is
      neither the previously described volume regulated release mechanism nor due to
      the reversal of the glutamate transporter.

PMID- 7643225
TI  - The role of free radicals and p53 in neuron apoptosis in vivo.
AB  - Apoptosis is a mechanism of cell death operative in the normal development and
      regulation of vertebrate tissues and organ cellularity. During the postnatal
      development of the mouse cerebellum, extensive granule neuron apoptosis occurs
      that may regulate the final granule cell to Purkinje cell stoichiometry observed
      in the adult. Cerebellar granule cells are highly sensitive to genotoxic agents
      such as gamma-irradiation and methylazoxymethanol during the first 2 weeks of
      postnatal development. We demonstrate that ionizing radiation induces extensive
      cerebellar granule cell death via apoptosis in vivo. In p53 null mice, however,
      the cerebellar granule cells do not undergo apoptosis in response to gamma
      irradiation. In mice heterozygous for the p53 allele, the granule cells apoptosis
      is delayed, indicating an intermediate response. The developmental apoptosis of
      cerebellar granule cells, however, occurs similarly in wild-type and p53 null
      mice. Therefore, neurons undergo p53-dependent and p53-independent apoptosis,
      depending upon the initiating stimulus that triggers DNA fragmentation. In
      contrast to x-ray damage, the extensive death of cerebellar granule cells induced
      by methylazoxymethanol was found to be independent of the DNA fragmentation
      characteristic of apoptosis, and was also independent of expression of p53.
      Ablation of neuron progenitor cells with genotoxic agents may occur by p53
      dependent apoptosis or by p53-independent mechanisms not associated with DNA
      fragmentation.

PMID- 7643226
TI  - Musings on work (or what's a nice girl like me doing in an office like this?)

PMID- 7643224
TI  - Protease nexin-1 and thrombin modulate neuronal Ca2+ homeostasis and sensitivity
      to glucose deprivation-induced injury.
AB  - Protease nexin-I (PN-1) is a 44 kDa serine proteinase inhibitor that rapidly
      inhibits thrombin by forming SDS stable complexes with serine at the catalytic
      site of the protease. Levels of both PN-1 and thrombin are increased in the brain
      in response to insults such as ischemia, suggesting roles in neural injury and
      repair processes. We now report that PN-1-protected cultured rat hippocampal
      neurons against glucose deprivation- induced damage (GDID), and the protection
      was abolished by equimolar thrombin. PN-1 reduced resting intracellular free
      calcium levels ([Ca2+]i) and attenuated the elevation of [Ca2+]i normally
      associated with GDID. Thrombin reduced neuronal survival and caused a significant
      increase in [Ca2+]i. Submaximally toxic levels of thrombin exacerbated GDID.
      Calcium responses to thrombin were attenuated in neurons contacting PN-1
      immunoreactive astrocytes. These findings suggest that PN-1 and thrombin play
      important roles in modulating neuronal calcium responses, and vulnerability, to
      metabolic/excitotoxic insults.

PMID- 7643227
TI  - Nursing assistive personnel in acute care. Framework for staff development.
AB  - Increasing numbers of nonlicensed personnel in acute care facilities are
      requiring staff development educators to examine their role in relation to the
      demands created by these positions. Continued pressures on healthcare delivery
      are causing nursing departments to redefine and restructure nursing care using
      assistive personnel positions. Interpreting standards, providing education for
      role implications and performance, and participating actively in change can
      influence outcomes for the nursing staff members affected. In this article, the
      author offers a framework for staff development educators to assess, organize,
      and plan activities for these workers.

PMID- 7643228
TI  - Design, implementation, and evaluation of an educational program for a new
      practice model.
AB  - Redesigning patient care delivery is vital to the quality of care delivered and
      has resulted in the development of new nursing practice models that use some form
      of "nurse extender." In this article, the authors describe the design,
      implementation, and evaluation of an educational program for a new nursing
      practice model at a medical center in the Southeast. The major focus of the
      educational program is the use of modules to train a new nontraditional nurse
      extender who works in partnership with an RN. The role of the partner in patient
      care was developed to expedite the provision of a variety of services at the
      bedside and to help the nurse deliver quality patient care. The training program
      consisted of five modules: fundamentals of nursing, selected respiratory therapy
      skills, selected physical therapy skills, electrocardiogram (EKG)/arrhythmia
      interpretation, and phlebotomy. A major factor in the success of the program was
      that it was carefully developed and evaluated to meet the needs of students and
      staff members. This program can serve as a model for other hospitals that plan to
      use nurse extenders.

PMID- 7643229
TI  - Managing the clinical affiliations of student nurses.
AB  - Problems are encountered with the clinical affiliation placements of student
      nurses accompanied by faculty members and practicum students, who function more
      independently. Mechanisms were initiated to better coordinate student learning so
      that it is congruent with clinical demands and human resources. The author
      describes effective policies for the facilitation of affiliation arrangements.

PMID- 7643230
TI  - The nurse as an educator.
AB  - The rapidly changing healthcare system offers challenges and opportunities for
      nurse educators. Increasing evidence of health promotion/consumer empowerment,
      cost containment, increase in chronic illness, and the continued expansion of
      medical technology requires nurses with broad educational competencies. These
      competencies include preceptoring, patient education, and formal presentation
      skills. In this article, the authors describe the development and implementation
      of a multifaceted staff development curriculum designed to support the nurse as
      an educator.

PMID- 7643231
TI  - From development to evaluation. Making a competency plan work.
AB  - Staff development educators face numerous challenges because of the Joint
      Commission on Accreditation of Healthcare Organizations (JCAHO) standards,
      continuous quality improvement, and economic constraints. For many, the most
      difficult challenge is complying with the JCAHO requirement for initial and
      ongoing competency, which must be validated for all nursing personnel. In this
      article, the authors describe how the educational nurse specialists of a tertiary
      care, regional referral medical center facilitated the development,
      implementation, and evaluation of a competency plan to validate initial and
      ongoing competency for all personnel within Nursing Services.

PMID- 7643232
TI  - Building nursing research expertise in a hospital setting. A group approach.
AB  - In this article, the authors describe the benefits of using a group approach to
      encourage nursing research among staff nurses. Individual learning and
      professional growth occurred in 10 nurses who collaborated on a research study on
      pain management. The authors take a "how to" look at the group approach as a
      mechanism for learning research and for professional development. Facilitator
      skills and group characteristics necessary for conducting a collaborative study
      are detailed.

PMID- 7643233
TI  - Computer-assisted instruction. A successful approach to mandatory annual review
      education.
AB  - Nurse educators have used various teaching strategies to comply with annual
      infection control and safety review requirements. In this study, the author
      investigated a computer-assisted instructional program that allows individualized
      education on the nursing unit during regular work hours. Significant time and
      cost savings to the institution were realized, and user satisfaction and
      compliance were high.

PMID- 7643234
TI  - Don't let advance directives "scare" you.

PMID- 7643235
TI  - An organization-wide approach to meeting Joint Commission staff education
      standards.

PMID- 7643236
TI  - Redesign of a nursing staff development department: past imperfect to future
      perfect.

PMID- 7643237
TI  - Unsaturated fatty acids regulate gene expression of cellular retinol-binding
      protein, type II in rat jejunum.
AB  - We have shown that cellular retinol-binding protein, type II (CRBP II) mRNA and
      its protein levels are elevated in the jejunum of rats fed a diet rich in long
      chain triacylglycerols. In the present study, we explored which types of fatty
      acids modulate CRBP II gene expression. Rats previously fed a low fat, high
      starch diet were force-fed a basal fat-free diet or the diet supplemented with
      0.21 mol/L of various fatty acids (i.e., caprylic, palmitic, stearic, oleic,
      linoleic and alpha-linolenic acids). Force-feeding a diet containing linoleic
      acid produced an elevation of CRBP II mRNA levels in rats in both a dose
      dependent (0.053-0.21 mol/L) and time-dependent (up to 6 h) manner. Among fatty
      acids tested, all unsaturated fatty acids (oleic, linoleic and alpha-linolenic
      acids) were able to enhance CRBP II mRNA levels by 54-63% within 6 h, whereas a
      medium-chain fatty acid (caprylic acid) and a saturated fatty acid (stearic acid)
      elicited little effect on the CRBP II mRNA levels; palmitic acid produced only a
      small elevation (16%) of the CRBP II mRNA level. Transcripts of both retinoid X
      receptor alpha and peroxisome proliferator-activated receptor (PPAR), which are
      thought to interact as a heterodimer with the cis-element located in the CRBP II
      promoter and to be activated by 9-cis retinoic acid and long-chain fatty acids,
      respectively, were constitutively expressed in the rat jejunum.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7643239
TI  - LDL receptor activity is down-regulated similarly by a cholesterol-containing
      diet high in palmitic acid or high in lauric and myristic acids in cynomolgus
      monkeys.
AB  - To determine the mechanisms whereby diets differing widely in fatty acid
      composition affect plasma LDL cholesterol and apolipoprotein B concentrations,
      LDL kinetics and receptor- and nonreceptor-mediated LDL catabolism were
      investigated in 27 cynomolgus monkeys fed diets containing 0.05 mg cholesterol/kJ
      and 40% fat energy as corn oil alone (unsaturated fat diet rich in oleic and
      linoleic acids), nonhydrogenated coconut oil alone (saturated fat diet, rich in
      lauric and myristic acids) or an oil blend (rich in palmitic acid). Consumption
      of the oil blend and saturated fat diets significantly elevated total
      cholesterol, LDL cholesterol and apolipoprotein B concentrations relative to the
      unsaturated fat diet and the saturated fat diet significantly increased plasma
      total cholesterol and LDL cholesterol compared with the oil blend diet. However,
      despite the greater increases in plasma total cholesterol, LDL cholesterol and
      apolipoprotein B in the saturated fat vs. the oil blend dietary group, the
      receptor-mediated LDL fractional catabolic rate was comparable in the oil blend
      and saturated fat diet groups. In addition, consumption of the oil blend or
      saturated fat diet increased the production rate of LDL apolipoprotein B and
      nonreceptor-mediated LDL apolipoprotein B transport (disposal) relative to the
      unsaturated fat diet. Our data, therefore, suggest that consumption of the oil
      blend or saturated fat diet elevated plasma total cholesterol and LDL cholesterol
      relative to the unsaturated fat diet, and the oil blend diet abundant in palmitic
      acid seems to have down-regulated the LDL receptor as much as a more saturated
      fat diet abundant in lauric and myristic acids.

PMID- 7643238
TI  - Animal and plant fats selectively modulate oxidizability of rabbit LDL and LDL
      mediated disruption of endothelial barrier function.
AB  - Enrichment of lipoproteins with fatty acids derived from animal and/or plant fats
      may modify the oxidizability of lipoproteins and their effects on endothelial
      barrier function. To test this hypothesis, rabbits were fed for 30 days diets
      containing 2 g corn oil/100 g diet (low fat diet) or low fat supplemented with 16
      g/100 g diet of corn oil, corn oil with added cholesterol, milk fat, chicken fat,
      beef tallow or lard. Compared with those fed the low fat, serum and LDL
      cholesterol concentrations were significantly lower in rabbits fed corn oil and
      greater in animals fed corn oil with added cholesterol or chicken fat. In
      contrast to the cholesterol data, lipid hydroperoxide levels were highest in
      oxidized LDL derived from rabbits fed corn oil or lard. LDL vitamin E levels were
      highest in rabbits fed corn oil with added cholesterol. The significant
      elevations in linoleic acid [18:2(n-6)] in serum and LDL may partially explain
      the high oxidizability of LDL in rabbits fed corn oil. LDL isolated from animals
      fed corn oil, lard or milk fat had significantly greater albumin transfer across
      cultured endothelial monolayers compared with those of the low fat diet group.
      Their oxidative modification further contributed to endothelial barrier
      dysfunction. Dietary cholesterol supplementation to the corn oil diet decreased
      oxidizability of LDL and partially protected the oxidized LDL-mediated
      endothelial cell dysfunction as compared with the corn oil diet group. These data
      suggest that beef tallow and chicken fat are the least atherogenic fats if
      oxidative modification of LDL is a critical issue in atherosclerosis.

PMID- 7643240
TI  - Retinoic acid repletion restores the number of leukocytes and their subsets and
      stimulates natural cytotoxicity in vitamin A-deficient rats.
AB  - Previously we reported that vitamin A-deficient rats have a low number of natural
      killer (NK) cells in their blood and spleen. The current studies were designed to
      address whether other cells of the immune system are also affected and whether
      dietary retinoic acid is able to reverse the changes caused by a deficiency of
      retinol and its metabolites. Total white blood cells, differential counts and
      spleen cell numbers were compared in vitamin A-sufficient rats (controls) and
      rats deficient in vitamin A, and lymphocyte and NK cell populations were
      identified and enumerated by flow cytometry. In comparison with control rats, the
      blood of deficient rats had three times the number of granulocytes, and fewer B
      lymphocytes (73% of control) and NK cells (38% of control). The numbers of
      splenic B cells (OX12+), CD5+ (OX19+) and CD4+ (W3/25+) T lymphocytes and NK
      cells (NKR-P1+) were also significantly reduced. When vitamin A-deficient rats
      were fed a retinoic acid supplement (4.2 mg all-trans retinoic acid/kg diet) for
      28 d, the numbers of blood granulocytes and NK cells equaled those of control
      rats and NK cell cytotoxicity was significantly elevated. Blood lymphocyte number
      was increased 40% due to increases of B cells and T cells of the CD5+, CD4+ and
      CD8+ subsets. These data indicate that vitamin A deficiency affects a number of
      cells of the immune system and that repletion with retinoic acid effectively
      reestablishes the number of circulating lymphocytes. In addition, retinoic acid
      may stimulate NK cell function.

PMID- 7643241
TI  - Consumption of excess vitamin A, but not excess beta-carotene, causes
      accumulation of retinol that exceeds the binding capacity of cellular retinol
      binding protein, type II in rat intestine.
AB  - We assessed the effects of excess dietary vitamin A or beta-carotene on the
      cellular retinol-binding protein, type II [CRBP(II)] level and activities of
      lecithin: retinol acyltransferase (LRAT) and acyl-CoA:retinol acyltransferase
      (ARAT) in rat intestine. Male rats were fed for 7 d diets containing amounts of
      retinyl acetate or beta-carotene that were 1 (control), 10, 100 and 1000 times
      the NRC recommended requirement. No responses of the jejunal CRBP(II) level to an
      intake of excess vitamin A or beta-carotene were observed. The unesterified
      retinol and retinyl palmitate concentrations in the jejunum were small in rats
      fed 10 times the vitamin A requirement but they were significantly greater in
      rats fed 100 and 1000 times the vitamin A requirement than in controls. The molar
      ratio of unesterified retinol/CRBP(II) was < 1 for the controls and the group fed
      10 times the vitamin A requirement, but > 3 for the group fed 100 times the
      requirement and > 19 for the group fed 1000 times the requirement. The LRAT
      activity was significantly greater in rats fed 1000 times the vitamin A
      requirement compared with all other groups, but ARAT activity was unaffected.
      Consumption of excess beta-carotene did not alter LRAT or ARAT activity, and led
      to a very small deposition of unesterified retinol and retinyl palmitate in the
      jejunum. Because CRBP(II) may play an important role in preventing the toxic
      effect of unbound retinol in the small intestine, consumption of excess vitamin A
      in amounts < 10 times the NRC recommended requirement may not cause a disturbance
      of the absorptive cell function.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7643242
TI  - Zinc deficiency decreases the concentration of N-methyl-D-aspartate receptors in
      guinea pig cortical synaptic membranes.
AB  - Zinc deficiency in guinea pigs decreases glutamate-stimulated calcium uptake in
      cortical synaptosomes. Glutamate not only stimulates calcium uptake but also
      potentiates the binding of the drug dizocilpine (MK-801) to an internal site of
      the N-methyl-D-aspartate receptor/calcium channel, a subtype of the glutamate
      receptor. The purpose of this study was to determine whether the effect of zinc
      deficiency on calcium uptake by glutamate-stimulated synaptosomes is related to N
      methyl-D-aspartate receptor number or function, as measured by MK-801 binding.
      Immature guinea pigs consumed a low zinc (< 1 mg/kg) diet ad libitum or an
      adequate zinc (100 mg/kg) diet, either ad libitum or restricted to maintain
      weight similar to that of the low zinc animals. Binding of MK-801 to cortical
      membranes was measured first in the presence of saturating concentrations of
      glutamate or N-methyl-D-aspartate in combination with glycine. Zinc deficiency
      significantly reduced the concentration of MK-801 binding sites (20%) regardless
      of the potentiating agonist used, but had no effect on binding affinity. The
      binding of MK-801 in response to 1, 10 and 100 mumol/L glycine, in the presence
      of 100 nmol/L glutamate, was then measured and found to be significantly reduced
      (12%). The results suggest that zinc deficiency decreases the number of
      functional N-methyl-D-aspartate receptor/channels in cortical membranes, probably
      because of impaired channel opening.

PMID- 7643243
TI  - Rat liver subcellular folate distribution shows association of
      formyltetrahydropteroylpentaglutamates with mitochondria and
      methyltetrahydropteroylhexaglutamates with cytoplasm.
AB  - The ternary complex method for the determination of folylpolyglutamates was
      combined with procedures for interconverting folate derivatives to measure 28
      different folate derivatives in the subcellular fractions of rat liver. Folates
      in the homogenate showed a typical distribution with nearly equal quantities of
      penta- and hexaglutamates and pteridine derivatives in decreasing order as
      follows: 1) methyl substituted folates [5-methyltetrahydropteroylglutamates], 2)
      unsubstituted folates [tetrahydropteroylglutamates + 5,10-
      methylenetetrahydropteroylglutamates], 3) formyl substituted folates [5
      formyltetrahydropteroylglutamates + 10- formyltetrahydropteroylglutamates + 5,10
      methenyltetrahydropteroylglutamates], and 4) oxidized folates
      [dihydropteroylglutamates]. In the homogenate the methyl substituted folates
      exhibited a higher hexa:pentaglutamate ratio than did the other pteridine
      derivatives. As the fractionation proceeded toward purer subcellular components,
      the methyl substituted folates were found almost exclusively in the soluble
      fraction, and this fraction also contained the higher hexa:pentaglutamate ratio
      characteristic of the methyl substituted folates. The plasma membrane, the
      microsomal and the nuclear fractions did not contain appreciable folate. The
      mitochondrial fraction contained primarily formyl substituted and unsubstituted
      folates, and these folates exhibited the lower hexa:pentaglutamate ratios. These
      data support the hypothesis that folate-dependent one-carbon metabolism is
      compartmentalized in the eukaryotic cell.

PMID- 7643244
TI  - Somatotropin enhances the rate of amino acid deposition but has minimal impact on
      amino acid balance in growing pigs.
AB  - This experiment was conducted to establish the influence of porcine somatotropin
      on tissue distribution and deposition rates of amino acids in growing pigs.
      Barrows were treated daily with buffer or porcine somatotropin (100 micrograms/kg
      body wt) when they weighed between 30 and 64 kg (eight pigs/group). Pigs were
      restrictively fed so that the average food intake was 1.86 kg/d. The corn-soybean
      meal-skim milk-based diet contained 18% crude protein and 1.2% lysine, and was
      designed to meet muscle amino acid ratio profile with respect to lysine as the
      first limiting amino acid for growth. Tissue levels of eighteen amino acids were
      determined on lyophilized samples that were appropriately hydrolyzed and analyzed
      by HPLC. The concentrations (mg/g dry wt) of all amino acids were greater in
      carcass, skin, head and empty body of porcine somatotropin-treated pigs; amino
      acid concentration in viscera was not influenced by porcine somatotropin.
      However, when the concentration of each amino acid was expressed on a per unit
      protein basis, the amino acid profiles of control and porcine somatotropin
      treated pigs were quite similar. The average deposition rate of each amino acid
      was increased approximately 67% by porcine somatotropin. When the deposition of
      each amino acid was calculated in relation to lysine, however, the pattern of
      amino acid utilization for growth was similar for control and porcine
      somatotropin-treated pigs; exceptions were arginine, glycine and tryptophan. The
      ratio of indispensable to dispensable amino acids that were deposited was also
      similar for control and porcine somatotropin-treated pigs. These data indicate
      that the synthesis rate of individual proteins can be influenced by porcine
      somatotropin, but the balance of amino acids remains largely unaffected,
      suggesting that the changes in protein and amino acid metabolism elicited by
      porcine somatotropin are consistent with normal growth processes.

PMID- 7643245
TI  - Biotin influences palatal development of mouse embryos in organ culture.
AB  - Maternal biotin deficiency is strongly teratogenic in CD-1 mice. The most common
      malformations are craniofacial and limb defects such as cleft palate,
      micrognathia and micromelia. The effect of biotin deficiency on palatal
      development in mouse embryos on d 12 of gestation was studied by culturing mouse
      embryonic palates in serum-free medium using a suspension culture system. In
      control embryos palatal processes developed to the fused stage after 72 h in
      culture. The fusion of palatal processes was further increased by the addition of
      biotin (10(-8) mol/L) to the medium. The addition of organic acids such as
      propionic, beta-methyl crotonic or beta-hydroxy isovaleric acids as well as
      avidin to the medium did not affect the stage of palatal formation. Cycloheximide
      completely blocked the fusion of palatal shelves. In embryos from biotin
      deficient mice, the incidence of fusion between the palatal shelves was < 7% and
      increased to > 30% when biotin (10(-8)-10(-6) mol/L) was added to the medium. The
      addition of fatty acids to the organ culture medium did not have any effect on
      the fusion of palatal processes. The incorporation of 35S-methionine into protein
      from biotin-deficient embryo explants was 88% of that in controls. The results
      indicate that biotin deficiency may interfere directly with synthesis of specific
      proteins and the formation of palatal processes.

PMID- 7643246
TI  - Night blindness is prevalent during pregnancy and lactation in rural Nepal.
AB  - The prevalence of night blindness during pregnancy and lactation was assessed in
      a sample of 426 women living in the rural terai of Nepal. These women were also
      examined for ocular signs of vitamin A deficiency. Among 241 lactating women,
      16.2% reported experiencing night blindness at some time during the pregnancy
      that produced the infant they were now breast-feeding. Among 185 pregnant women,
      8.1% reported being night-blind at the time of the interview. The odds of night
      blindness in the current pregnancy were six times greater for women who reported
      night blindness in their previous pregnancy. Night-blind women were more likely
      to come from households with lower socioeconomic status. Teenage women and those
      over the age of 30 were at highest risk, particularly those of higher parity
      within these age groups. Vitamin A deficiency, for which night blindness is a
      marker, seems to be a problem in this population of pregnant and lactating women,
      with potential health consequences for women and their infants.

PMID- 7643247
TI  - All-trans beta-carotene preferentially accumulates in human chylomicrons and very
      low density lipoproteins compared with the 9-cis geometrical isomer.
AB  - Following ingestion of a beta-carotene isomer mixture (Betatene) containing
      nearly equal amounts of all-trans and 9-cis beta-carotene (all-trans/9-cis beta
      carotene ratio approximately 1.5), concentrations of all-trans beta-carotene
      increased for 6 or 8 h in the chylomicron fraction of plasma from four of seven
      human subjects. A substantially lower increase in the 9-cis beta-carotene
      concentration was observed, with the accumulation of the all-trans isomer being
      10- to 50-fold higher than that of the 9-cis isomer, calculated on the basis of
      the beta-carotene isomer pattern in the ingested mixture. A similar effect was
      observed in the VLDL fraction. Three of the seven subjects did not respond to
      beta-carotene ingestion. In the subjects that did respond, the all-trans/9-cis
      beta-carotene ratios in chylomicrons and VLDL suggest an efficient isomer
      selective mechanism for intestinal uptake across the mucosa or very rapid
      elimination into tissues.

PMID- 7643248
TI  - Hypocholesterolemic action of eritadenine is mediated by a modification of
      hepatic phospholipid metabolism in rats.
AB  - The hypocholesterolemic action of eritadenine, a compound found in the mushroom
      Lentinus edodes, was investigated in relation to its influence on phospholipid
      metabolism in the liver of rats fed diets containing different amounts of choline
      chloride (0, 2 and 8 g/kg diet). The time-dependent effect of eritadenine
      supplementation was also investigated. Eritadenine supplementation (50 mg/kg
      diet) significantly decreased the phosphatidylcholine
      (PC):phosphatidylethanolamine (PE) ratio in liver microsomes and the S
      adenosylmethionine (SAM):S-adenosylhomocysteine (SAH) ratio in the liver, in
      addition to the plasma cholesterol concentration, irrespective of dietary choline
      levels. There was a significant correlation between the plasma cholesterol
      concentration and the liver microsomal PC:PE ratio. Although eritadenine caused
      fatty liver when added to the diets containing 0 or 2 g/kg choline chloride, a
      high level (8 g/kg) of choline chloride fully prevented the eritadenine-induced
      fatty liver without diminution of hypocholesterolemic action. Both the PC:PE
      ratio and the SAM:SAH ratio decreased significantly prior to the decrease in the
      plasma cholesterol concentration (1 d vs. 2 d after) in response to eritadenine
      supplementation, supporting the hypothesis that the alteration of hepatic
      phospholipid metabolism may be a cause of the hypocholesterolemic action of
      eritadenine. These observations suggest that the essential hypocholesterolemic
      action of eritadenine might be associated with a modification of hepatic
      phospholipid metabolism rather than with the PC deficiency, due to the inhibition
      of PE N-methylation.

PMID- 7643249
TI  - The utilization of lupin (Lupinus angustifolius) and faba bean globulins by rats
      is poorer than of soybean globulins or lactalbumin but the nutritional value of
      lupin seed meal is lower only than that of lactalbumin.
AB  - The effects of dietary sweet lupin (Lupinus angustifolius, Unicrop) seed meal or
      its insoluble fiber (nonstarch polysaccharides + lignin) on performance,
      digestibility and nitrogen utilization in growing rats were studied in four
      experiments. Globulin proteins isolated from lupin, faba bean (Vicia faba L.
      minor) or soybean (Glycine max) were also incorporated into purified diets as
      replacements for lactalbumin (control) and the nutritional effects were
      evaluated. Isocaloric, legume-based diets supplemented with amino acids were
      used. Final weight gain, gain:feed ratios, nitrogen retention and net protein
      utilization of the animals fed whole lupin meal-based diets for 10 d were
      inferior to those of controls. In contrast, adding lupin insoluble fiber to a
      control diet produced no adverse effects. Ileal starch and apparent nitrogen
      digestibilities, and fecal digestibility of starch in lupin-fed rats were higher
      than those of controls, but fecal true nitrogen digestibility was lower.
      Replacement of lactalbumin with globulin proteins from lupin or faba bean
      depressed food intake and protein utilization, but only performance was affected
      by consumption of soybean globulins. Rats consuming lupin or faba bean globulins
      excreted significantly more nitrogen, particularly as urea through the urine.
      This did not occur in rats fed soybean globulins. Urea concentration in plasma
      was higher in rats fed diets containing lupin meal or legume globulins. The
      concentrations of urea, arginine and ornithine in plasma increased significantly
      compared with control values after 3 to 9 h of a lupin diet. After 9 h, plasma
      lysine was also decreased. We concluded that the main reasons for the low
      nutritional value of sweet lupin seed meal are likely to be related to the
      chemical structure of the globulin proteins and their adverse effects on growth
      and nitrogen metabolism, and not to any known antinutritional factor or poor
      digestibility.

PMID- 7643250
TI  - Absorption of fructose by isolated small intestine of rats is via a specific
      saturable carrier in the absence of glucose and by the disaccharidase-related
      transport system in the presence of glucose.
AB  - Previous studies have shown that the absorption of fructose is aided by
      simultaneous ingestion of glucose. The aim of the present study was to reproduce
      this finding in vitro to better understand the mechanism of the effect of glucose
      on absorption of fructose. The phenomena could not be reproduced with everted
      sleeves of rat intestine or brush border vesicles. In a perfused segment of
      isolated intestine, it was possible to demonstrate that the transport of fructose
      was accelerated when glucose was present in the perfusion medium. The enhanced
      transport was inhibited by sucrose and also by acarbazone, an inhibitor of
      intestinal alpha-disaccharidases. Phlorizin had no effect on the transport of
      fructose. The results of these studies indicate that there is a specific carrier
      for fructose saturated with a low concentration of the sugar, and that in the
      presence of glucose there is joint absorption of the two sugars by the
      disaccharidase-related transport system.

PMID- 7643251
TI  - Consumption of carbohydrate or medium- or long-chain triglycerides by unfed rats
      exerts different protein-sparing effects.
AB  - Consumption of nonprotein energy is reported to promote nitrogen retention (the
      protein-sparing effect). The present study was conducted to determine whether
      consumption of medium-chain triglycerides (MCT), long-chain triglycerides (LCT)
      or carbohydrate by unfed rats would exert different protein-sparing effects over
      48 h. The amounts of MCT, LCT and carbohydrate were adjusted to be isoenergetic.
      The control group received only water. The urinary excretion of urea in the
      groups fed carbohydrate or MCT was significantly lower than in the LCT and
      control groups within the first 24 h. Urinary excretion of urea in the group fed
      LCT was similar to that of the control group for the first 24 h but was
      significantly lower after 48 h. Liver serine dehydratase activities in the groups
      fed MCT or LCT were similar, although they were significantly lower than in the
      control group. Serine dehydratase activity in the carbohydrate-fed group was the
      lowest. Liver L-lysine-2-oxoglutarate reductase activity was significantly lower
      in the groups fed carbohydrate, MCT or LCT than in the control group. Rats fed
      MCT had the lowest plasma concentrations of lysine and branched-chain amino
      acids. However, the plasma concentration of glutamic acid in the rats fed MCT was
      the highest. These results indicate that rats fed MCT, LCT or carbohydrate
      exhibit different protein-sparing effects and that the difference between rats
      fed MCT and those fed LCT is not attributable to differences in amino acid
      degrading enzymes. Consumption of MCT may conserve some amino acid-derived
      nitrogen as glutamic acid.

PMID- 7643252
TI  - The time course of adaptation of intestinal nutrient uptake in mice is
      independent of age.
AB  - Slow adaptive responses are typical of aged animals. The pace of intestinal
      adaptation is relatively rapid in young mice but is not known in aged mice. In
      this study, we determined the time course of adaptation of intestinal nutrient
      uptake to abrupt and substantial changes in levels of dietary nutrients in young
      and aged mice. Mice (24-mo-old and 6- to 7-mo-old, controls) were fed a no
      carbohydrate, high protein diet for 7 d and then were switched to a high
      carbohydrate, low protein diet for 0, 1, 2, 3 and 5 d. Body weights, feeding
      rates, intestinal weights and lengths were all independent of diet. Within 1 d
      after the switch in diet, glucose and fructose uptakes increased in young and
      aged mice. In both age groups, alanine and aspartate uptakes decreased
      significantly, whereas proline, leucine and lysine uptakes were independent of
      diet. In both age groups, total intestinal absorptive capacity for glucose and
      fructose increased overnight by about 70 and 200%, respectively. Previous studies
      linked time course of adaptation to rates of enterocyte proliferation. Rates of
      enterocyte turnover and migration along the crypt/villus axis of proximal, middle
      and distal small intestine were independent of age. Thus, the time course of
      intestinal adaptation in aged mice remains largely unchanged from that in young
      mice, probably because rates of enterocyte proliferation seem independent of age.

PMID- 7643253
TI  - Chronic protein restriction does not alter energetic efficiency or brown adipose
      tissue thermogenic capacity in genetically obese (fa/fa) Zucker rats.
AB  - Attenuated regulatory thermogenesis in genetically obese (fa/fa) Zucker rats
      involves an impaired capacity to increase sympathetic drive to brown adipose
      tissue in response to dietary stimuli. Young, growing lean rats fed a low protein
      diet reduce energetic efficiency to compensate for elevated energy intake;
      however, it is not known if obese rats adapt similarly to chronic protein
      restriction by decreasing energetic efficiency and whether this would be
      accompanied by increased brown adipose tissue thermogenic capacity. Lean (Fa/Fa)
      and obese Zucker rats were either protein-restricted (protein 8% of total energy)
      or fed a control diet (21% protein) starting at age 5 wk. At 9 wk, oxygen
      consumption (VO2) was measured in response to an intubated meal of mixed
      macronutrient composition. Mass-adjusted food intake (i.e., food intake/body
      weight 0.67) was greater in protein-restricted than in control lean rats, but not
      different due to diet in obese rats. Mass-adjusted brown adipose tissue
      uncoupling protein levels were more than 100% greater in protein-restricted vs.
      control lean rats, but not different between protein-restricted and control obese
      rats. The uncoupling protein level was not significantly different in control
      lean vs. obese rats. Energetic efficiency was 40% lower in protein-restricted vs.
      control lean, but not different in obese rats; however, the efficiency of protein
      utilization was significantly greater in obese protein-restricted than in obese
      control rats. Meal-induced energy expenditure (VO2) did not differ significantly
      due to diet or genotype. In conclusion, protein restriction led to overfeeding in
      lean rats which appeared to enhance brown adipose tissue thermogenic capacity and
      decrease energetic efficiency. Protein efficiency increased to more than two
      times its original value in obese (fa/fa) rats, but otherwise no metabolic
      accommodation in the capacity for regulatory thermogenesis was observed in this
      genotype.

PMID- 7643254
TI  - Uptake and metabolism of riboflavin-5'-alpha-D-glucoside by rat and isolated
      liver cells.
AB  - The effect of riboflavin alpha-D-glucoside, isolated from rat liver, on the
      uptake of riboflavin was studied using freshly isolated rat liver cells. The
      transport characteristics and metabolic fate of the glucoside were also
      determined using the radioactive compound. The initial (1-min) uptake of 1
      mumol/L [3H]riboflavin glucoside (2.90 +/- 0.29 pmol/10(6) cells) was higher than
      that of 1 mumol/L [3H]riboflavin (1.35 +/- 0.30 pmol/10(6) cells). However, the
      accumulation of glucoside after 60 min was significantly lower than that of
      riboflavin. The presence of up to 30 mumol/L glucoside had no significant effect
      on the initial uptake of [3H]riboflavin (3 mumol/L, 10(9) cells/L). Measurement
      of the kinetic parameters for glucoside gave an apparent Kt value of 83.4 +/-
      12.4 mumol/L and a Vmax of 208.6 +/- 17.9 pmol/(10(6) cells.min). Decreases in
      the temperature of incubation decreased uptake rate. Replacement of Na+ with
      other monovalent cations did not affect uptake. The presence of D-glucose (1
      mumol/L to 5.5 mmol/L) had no inhibitory effect on uptake of 1 mumol/L
      [3H]riboflavin glucoside. The results indicate that the transport of riboflavin
      glucoside may not involve the transport mechanisms for riboflavin or D-glucose.
      Metabolic studies with isolated hepatocytes showed that the glucoside was
      hydrolyzed to yield riboflavin upon entry into the cell. The vitaminic efficiency
      of this compound was tested by feeding it to growing male rats. These experiments
      indicate that the glucoside and free riboflavin are comparable sources of the
      vitamin.

PMID- 7643255
TI  - Dietary protein quality alters ornithine decarboxylase activity but not vitamin B
      6 nutritional status in rats.
AB  - Weanling male rats were fed diets that varied in protein quality (casein or wheat
      gluten) and vitamin B-6 (0.0, 0.5, 1.0 and 1.5 mg pyridoxine HCl/kg diet) to test
      the hypotheses that low protein quality would depress vitamin B-6 nutritional
      status and that activity of ornithine decarboxylase (ODC) would be a sensitive
      functional indicator of vitamin B-6 nutritional status. The wheat gluten diet
      depressed body weight gain approximately 17% at higher vitamin B-6 levels, as
      expected. However, vitamin B-6 nutritional status was not worse in gluten-fed
      compared with casein-fed groups, as evidenced by static measures (B-6 vitamer
      concentrations in plasma and tissues) and a functional indicator (tryptophan load
      test). The activity of ODC (holo- and total) in liver, kidney and small intestine
      did not vary significantly at the three higher levels of vitamin B-6 intake. In
      groups fed casein, total ODC activity in these tissues was two- to fivefold
      higher in rats fed diets containing 0.0 mg vitamin B-6/kg compared with higher B
      6 levels, without corresponding differences in ODC mRNA abundance in liver and
      kidney. Concentrations of B-6 vitamers (except pyridoxal phosphate in plasma)
      increased linearly with dietary vitamin B-6 in plasma, liver, kidney and
      intestine. These data suggest that low quality protein fed as wheat gluten
      suppresses growth but not vitamin B-6 nutritional status, and that ODC activity
      is not a sensitive functional indicator of marginal vitamin B-6 status.

PMID- 7643256
TI  - Research.

PMID- 7643257
TI  - Breastfeeding.

PMID- 7643258
TI  - NICU care.

PMID- 7643259
TI  - Families and nurses: building partnerships for growth and health.
AB  - The newborn's social and emotional development depends on a relationship in which
      attention, affect, and information are shared with the mother. Young,
      disadvantaged families may encounter characteristic difficulties in maintaining
      these social relationships. Partnerships for health between nurses and
      disadvantaged clients require sharing similar relationships, and they present
      parallel challenges.

PMID- 7643260
TI  - Is there scientific support for the use of juice to facilitate the nonstress
      test?
AB  - In this article, a review of the literature is presented regarding the practice
      of administering fruit juice to facilitate the nonstress test (NST). Seven
      studies were found that investigated the relationship between the administration
      of natural or artificial glucose and the NST. No support was found for the use of
      juice or glucose to facilitate the NST as commonly administered in practice or as
      noted in textbooks. Therefore, the practice and textbook references to it should
      be questioned. The use of rituals undermines the professionalism of nursing
      practice.

PMID- 7643261
TI  - Screening methods for postpartum depression.
AB  - Nine to fifteen percent of women who have recently given birth experience
      postpartum depression; however, only a small portion of these women are
      identified as depressed by health professionals. To improve this poor detection
      rate, a new screening tool, the Postpartum Depression Checklist (PDC), was
      constructed, based on the findings of two qualitative studies. The PDC is a
      simple, practical device for use by health professionals that provides an
      opportunity to engage a woman actively in a dialogue about her experiences with
      the 11 symptoms included on the checklist. Its use by health professionals during
      the 1st year postpartum may help to ensure that mothers who experience postpartum
      depression receive treatment.

PMID- 7643262
TI  - The lived experience of self-transcendence in women with AIDS.
AB  - OBJECTIVE: To describe the lived experience of self-transcendence in women with
      AIDS, associated with increased sense of meaning and purpose, well-being, self
      esteem, and connectedness with self and/or others. DESIGN: Exploratory
      descriptive, using phenomenological research methods for the study approach, data
      collection, and data analysis. SETTING: One written description and nine
      audiotaped interviews of self-transcendence experiences were provided by women
      with class IV HIV infection (AIDS). PARTICIPANTS: Ten women recruited by nurses
      at an AIDS family clinic and through a flyer at the AIDS Support Group House in
      Seattle. OUTCOMES: Participant descriptions indicated that women with AIDS
      continue to find meaning and purpose in their lives through experiences of
      receiving from others, giving to others, and maintaining hope. RESULTS: The
      findings support the theory that self-transcendence views and behaviors are a
      source of mental health at the end of life. CONCLUSIONS: The findings suggest
      several ways nurses may help women with AIDS discover or make meaning and purpose
      in their lives.

PMID- 7643264
TI  - Cultural meanings of childbirth.
AB  - In no known culture in the world is childbearing treated with indifference.
      Cultural beliefs about and values associated with childbearing touch all aspects
      of social life in any given culture. Such beliefs and values lend perspective to
      the meaning of childbirth to the childbearing woman. Having the opportunity to
      share the woman's perceptions of the meaning of childbearing may foster the self
      actualization, promote maternal role attainment, and improve her relationship
      with her significant other and enrich the family perspective. Nursing
      interventions across the childbearing year should be culturally sensitive to
      promote positive outcomes for the woman and her family.

PMID- 7643263
TI  - Indwelling versus intermittent feeding tubes in premature neonates.
AB  - OBJECTIVE: To determine the effect of indwelling versus intermittent feeding tube
      placement on weight gain, apnea, and bradycardia in premature neonates. DESIGN:
      Eligible subjects were assigned randomly to either feeding tube method. Each
      subject was followed for 6 days. SETTING: The study was conducted in a secondary
      level neonatal intensive-care unit (NICU), a tertiary level NICU in a perinatal
      center, and a tertiary level NICU in a referral center. PATIENTS/PARTICIPANTS:
      Neonates who were 24-34 weeks gestational age, developmentally appropriate for
      gestational age, medically stable, on full enteral feedings through an orogastric
      or a nasogastric tube, and not fluid restricted. Ninety-three neonates were
      enrolled--49 indwelling group and 44 in the intermittent group. Nine neonates did
      not complete the study. INTERVENTIONS: Nasogastric indwelling feeding tubes were
      placed and left in site for up to 3 days. Orogastric intermittent feeding tubes
      were placed for each feeding and removed at completion of the feeding. MAIN
      OUTCOME MEASURES: Weight gain, apnea, and bradycardia. RESULTS: Members of both
      groups had similar demographic characteristics, clinical problems, and
      nutritional intake. No statistical differences were found between the two groups
      in weight gain or episodes of apnea and bradycardia. CONCLUSIONS: There were no
      statistically or clinically significant differences between the two groups. The
      intermittent method of feeding is more expensive. Because no clinical differences
      were found, the type of tube placement chosen for feeding the premature infant
      may be based on economics.

PMID- 7643265
TI  - Culturally sensitive perinatal care for southeast Asians.
AB  - This article presents strategies for providing perinatal care to Southeast Asians
      living in the United States and Canada. The population is described, and
      attention is paid to how their past and continued lifestyle contribute to health
      problems. Traditional healing beliefs and practices, especially those pertaining
      to childbearing, are discussed. A demonstration project in Long Beach,
      California, is described as a model for delivering culturally sensitive care.

PMID- 7643266
TI  - Birth in the Japanese context.
AB  - A qualitative study of the experiences of 20 American women who gave birth in
      Japan is reported. Five interrelated issues that were important to this group of
      women emerged from the interview data: a sense of isolation, the need for
      security, the need to regain control, the need for affirmation, and the need for
      cultural support. These findings are interpreted within a framework of stress and
      coping, maternal identification, and cultural adaptation theories. These women
      were dually stressed by the demands of childbearing and transcultural migration.
      Implications for clinical practice are suggested.

PMID- 7643267
TI  - Caregiver-child interactions in Japan, Taiwan, and the United States.
AB  - This study reports the results of an investigation of the contact stimulation
      between caregivers and their children in 409 dyads (38 in Japan; 100 in Taiwan;
      and 271 in the United States). An instrument was used to record quantitative and
      qualitative data of the dyads in the three countries. A time-sampling procedure
      of 1 minute of observation and 1 minute of recording, with a minimum of 15
      minutes and a maximum of 30 minutes, per dyad was used for data collection. The
      findings indicate significant differences at the p = 0.0001 level among the three
      cultural groups on the following variables: proximity, clothing, soothing,
      playing with the child, reading to the child, holding the child, and behavior
      toward a sleeping child.

PMID- 7643268
TI  - A contrast of mothering behaviors in women from Korea and the United States.
AB  - In both the United States and Korea, culture heavily influences a mother's
      behavior toward her infant. Differences between these two cultures are explored,
      based on the author's experiences and work in both environments. This comparison
      includes a number of points of departure. The American culture encourages
      autonomous and independent behaviors from infants, whereas in the Korean culture,
      mothers tend to view infants as passive and dependent. American mothering is
      individually fashioned and relies on the expertise of health care providers.
      Conversely, the Korean culture is highly ritualistic, so mothering is molded more
      by societal rules than by individual design, and professional advice is less
      sought for guidance than is folklore information. American mothers tend to rear
      their infants in a nuclear family setting, whereas Korean mothers rear their
      infants in an extended family or at least in a highly social environment.
      Implications for American nurses who provide perinatal care for Korean immigrant
      women are discussed.

PMID- 7643269
TI  - Craniofacial trauma and cerebrospinal fluid leakage: a retrospective clinical
      study.
AB  - PURPOSE: The study examines the efficacy of antibiotic treatment in patients with
      traumatic cerebrospinal fluid (CSF) leakage and identifies a consistent clinical
      approach for better management of these patients. PATIENTS AND METHODS: A
      retrospective study of traumatic CSF leakage in 88 patients with craniofacial
      fractures was performed. The mechanism of injury, etiology and source of leakage,
      decision to treat conservatively (without surgery) versus aggressively (with
      surgery), decision to use early versus late repair, and decision to provide
      prophylactic antibiotic coverage were recorded. Both timing of repair and the
      decision to use antibiotics were compared with the incidence of meningitis
      resulting from CSF leakage. RESULTS: Of 48 patients treated with antibiotics,
      5(10.4%) developed meningitis. In the remaining 40 who were not treated with
      antibiotics, only one patient acquired meningitis. Five of 53 (9.4%) patients
      with conservative treatment developed meningitis versus 1 of 35 (2.9%) after
      aggressive treatment. CONCLUSION: There was no statistically significant
      difference in the rate of occurrence of meningitis between the conservative and
      the aggressive treatment group. However, the data suggest that there may be no
      benefit in treating these patients with antibiotics to prevent meningitis,
      whereas aggressive treatment and early repair of facial fractures may, in fact,
      be helpful.

PMID- 7643270
TI  - Facial morphometry of television actresses compared with normal women.
AB  - PURPOSE: The object of this investigation was to determine whether young women
      considered as beautiful differ in their three-dimensional facial characteristics
      from normal women of the same age and race. METHODS: The three-dimensional
      coordinates of 22 standardized soft-tissue facial landmarks were automatically
      collected in two groups of women using a noninvasive instrument. The first group
      consisted of 10 white television actresses selected only on the basis of their
      soft-tissue facial appearance ("beautiful" group); the second group included 40
      healthy, white women selected according to criteria of dentofacial normality
      ("normal" group). The x, y, and z coordinates of the points collected on each
      woman were used to calculate several three-dimensional angles, linear distances,
      linear distance ratios, and facial volumes. RESULTS: The facial morphometric
      characteristics within the beautiful group were more uniform than within the
      normal group. On average, the beautiful women had a larger forehead, a larger
      middle facial third relative to the total face, a wider (left-right dimension)
      and less deep (anteroposterior dimension) face, a smaller nose, and a less convex
      face (in both the sagittal and transversal planes) than the normal women.
      CONCLUSION: The three-dimensional cutaneous facial characteristics of the
      beautiful women were significantly different from the characteristics of the
      normal women.

PMID- 7643271
TI  - Age-related changes in the human mandibular condyle: a morphologic, radiologic,
      and histologic study.
AB  - PURPOSE: This study determined the osteoarthrotic changes in the human mandibular
      condyle in relation to aging and the loss of dental occlusal contacts. MATERIALS
      AND METHODS: Thirty-four condyles obtained at autopsy were studied
      morphologically, radiologically, and histologically. RESULTS: With advancing age,
      the articular surface of the mandibular condyle morphologically showed severe
      degenerative changes. The condyles with these changes tended to be from the side
      of the mandible with minimal areas of occlusal contact. Radiographically, an
      irregularity of the cortical bone plate was most commonly seen in the fifth and
      sixth decades, whereas a polygonal or flattened structure was mainly observed
      after the seventh decade. CONCLUSION: The histologic findings suggest that a
      decrease in the cellular components with advancing age may play a critical role
      in the development of degenerative changes.

PMID- 7643272
TI  - Nasal symmetry after primary cleft lip repair: comparison between Delaire
      cheilorhinoplasty and modified rotation-advancement.
AB  - PURPOSE: Periosteal musculoaponeurotic (PMAS) reconstruction is a key objective
      in primary repair of the cleft lip. The reconstructed muscles provide a sound
      framework and stimulus for development of the nasolabial region. In this study
      two primary cleft lip repair techniques were retrospectively studied to determine
      if one [Delaire (Del)] which involves PMAS repair around the cleft results in
      more nasolabial symmetry than a technique that does not fully addressed the
      musculature [modified Rotation-Advancement, (mR-A)]. PATIENTS AND METHODS: Four
      and 5-year-old children with complete unilateral cleft lip and palate were
      recalled for study (n = 33 children; Del group, 16; mR-A group, 17). Clinical and
      photographic records were obtained and anthropometric analyses determined for
      comparison between groups. RESULTS: In the mR-A group, noses had more
      asymmetrical tips, were shorter, projected less, and tended to be flatter or
      wider. Nasal indices tended to support these findings. Nasal height was similar
      for the mR-A and Del groups. When comparing cleft versus noncleft sides, alar
      width and length and nostril length were significantly different for both cleft
      groups. CONCLUSIONS: It appears from this study that reconstruction of the PMAS
      of the nasolabial region during primary cleft lip repair may positively influence
      growth and development of the nose in unilateral cleft lip and palate patients.

PMID- 7643273
TI  - Frontonasal suture expansion in the rabbit using titanium screws.
AB  - PURPOSE: This study investigated the ability to use titanium screws to provide
      stable skeletal points in the growing craniofacial region of the rabbit for
      suture expansion. These screws provided sites for direct application of external
      forces to alter growth and anatomic form. MATERIAL AND METHODS: Twenty-one
      rabbits (30 days old) were divided into three groups: control (n = 9),
      experimental (n = 9, and sham (n = 3). Four four-holed AO/ASIF commercially pure
      titanium craniofacial plates were contoured into an L-shape with a 90 degree
      angle at the midpoint. The plates were placed bilaterally in the frontal and
      nasal bone sites and secured with 2.0-mm diameter, 4-mm long, commercially pure
      titanium screws in both the sham and experimental groups. After 4 week of
      healing, a spring mechanism with a distraction force of 55 g was activated
      between ipsilateral plates and across the frontonasal sutures bilaterally in the
      experimental group for 5 weeks. No force was applied between the plates in the
      sham group. A preliminary evaluation of the bone-implant interface and the
      changes in the suture was done histologically. Morphologic changes were measured
      using cephalometric radiographs and direct anatomic measurements. RESULTS: The
      experimental group showed a significant increase in growth across the frontonasal
      suture in comparison with the sham group (P < .05). In addition, an increase in
      the length of the nasal and frontal bones in the expanded group was observed in
      comparison with the control and sham groups (P < .05). Histologically, a mixture
      of woven and lamellar bone was seen in the suture region and lamellar bone was
      seen in the screw-bone interface. CONCLUSION: This study indicates that titanium
      screws in the developing rabbit skull can provide stable sites for the direct
      application of external forces, producing secondary changes in skeletal
      morphology. This laboratory models provides a useful system for the further study
      of growth modification using such external mechanical forces.

PMID- 7643274
TI  - Structural properties of mandibular bone following application of a bone plate.
AB  - PURPOSE: Similarities in strain patterns between long bones and the mandible
      suggest that plates may induce stress shielding, resulting in deleterious long
      term changes. This study is an investigation of the use of bone plates on the
      mandible in four adult rhesus monkeys. MATERIAL AND METHODS: A stainless steel
      plate was attached facially along the inferior border of each mandibular corpus.
      On the left, a thick (2.5-mm) plate was engaged with four screws. On the right, a
      thin (0.5-mm) plate was attached with one screw. Monkeys were killed a year after
      plate placement. At the beginning and end of the experiments, bone strain was
      recorded inferior to each bone plate during evoked maximal incisal clenching.
      After death, bone was removed from the mandibles around and under the plates and
      examined. Gross dimensions and density were measured. An ultrasonic technique was
      used to measure the material properties, including the elastic and shear moduli.
      RESULTS: Bone strain inferior to the plates was reduced by 34% to 53% after
      attachment of the thick plates. Little change in strain was found after
      attachment of the thin plates. However, no significant differences in structural
      or mechanical measurements, such as density, cortical thickness, elastic and
      shear moduli, and Poisson's ratios, were detected between the two sides in each
      monkey. CONCLUSION: Long-term placement of bone plates, and the resulting stress
      shielding, were found to result in structural changes in the mandibular corpus.

PMID- 7643275
TI  - An experimental study of three methods of lingual nerve defect repair.
AB  - PURPOSE: This study compares three methods of lingual nerve defect repair.
      MATERIALS AND METHODS: The recovery of the mechanosensitive and thermosensitive
      afferent fibers in the lingual branch of the trigeminal nerve in cats was studied
      using electrophysiological techniques 24 weeks after the removal of a segment of
      lingual nerve and repair of the defect by one of three methods. The nerve gap was
      closed by either stretching the nerve ends together and repairing under tension,
      insertion of a sural nerve graft, or use of a freeze-thawed muscle graft. The
      characteristics of the regenerated fibers were investigated and the data were
      compared with that from normal control animals. RESULTS: After nerve repair,
      integrated whole-nerve activity evoked by thermal (cold) stimulation of the
      tongue was smaller than in the controls, but there were no differences between
      the repaired groups. However, recordings made from single axons in filaments
      dissected from the nerve revealed differences between the groups; the units were
      less sensitive after either method of grafting than after stretch repair.
      CONCLUSIONS: It is concluded that repair of a short gap in the lingual nerve by
      stretch repair with an end-to-end anastomosis, even with some degree of tension,
      is followed by better recovery than by grafting. However, where a graft is
      necessary, a similar level of recovery will result from use of a frozen muscle
      graft or a sural nerve graft.

PMID- 7643276
TI  - The effect of electrical perturbation on osseointegration of titanium dental
      implants: a preliminary study.
AB  - PURPOSE: Successful osseointegration of titanium dental implants is decreased in
      areas of poor bone volume and density. Low amperage direct current (LADC) has
      been shown to perturb bone cells, which in turn promotes bone growth. The purpose
      of this experiment was to evaluate the effect of LADC on the osseointegration of
      endosseous titanium dental implants. MATERIALS AND METHODS: Two implant sites
      were prepared in the body of the mandible of five rabbits by an extraoral
      approach. An LADC-stimulated 3.75 x 7 mm-titanium implant was placed in one site
      and an identical control implant was inserted on the contralateral side. A
      sterilized silicone-encased power pack producing 7.5 +/- 0.2 uA and 1.35 +/- 0.01
      V was placed in a submandibular pouch. The active cathode lead was attached to
      the LADC implant and the anode was placed in the mandible 5 mm distal to the
      implant. Nonactive leads were similarly connected to the control implant. Twenty
      eight days after placement, the implants were removed using a torque wrench, and
      the bone surrounding the implants was examined both microscopically and
      radiographically. RESULTS: The average force to initial rotation was 1,320 +/-
      880 g/cm for the LADC-stimulated implants and 1,290 +/- 238 g/cm for the control
      implants. This was significantly different by t test (P = .94). Light microscopic
      evaluation demonstrated a mixture of compact and woven bone and fibrous tissue
      adjacent to both groups of implants. Histomorphometric analysis demonstrated an
      average percent of bone in relation to the total tissue adjacent to the control
      implants of 33.5 +/- 15.4 and 40.2 +/- 4.8 for the LADC-stimulated implants (not
      significantly different, t test, P = .39). CONCLUSION. It was concluded that LADC
      as used in this study does not positively affect the healing of bone. Its ability
      to enhance bone growth around titanium dental implants needs further
      investigation.

PMID- 7643277
TI  - Intra-articular disc displacement. Part I: Its questionable role in
      temporomandibular joint pathology.

PMID- 7643278
TI  - Intra-articular disc displacement Part II: Its significant role in
      temporomandibular joint pathology.

PMID- 7643279
TI  - Diagnosis and treatment of intracranial complications of paranasal sinus
      infections.
AB  - Complications and local extension of paranasal sinus infections most often
      involve the orbit and periorbita. Because of the widespread use of antibiotics
      since World War II, intracranial extension of maxillofacial sinusitis is rarely
      seen today. Nevertheless, the clinician must be aware of the potential for these
      complications, because late recognition of this condition and delays in treatment
      can increase morbidity and mortality rates. A comprehensive, current review of
      sinogenic intracranial complications is presented, with illustrative cases of
      brain abscess, subdural empyema, meningitis, cavernous sinus thrombosis, epidural
      abscess, and osteomyelitis. The mechanisms and potential for intracranial spread
      of infection from the frontal, sphenoid, and ethmoid sinuses are discussed in
      detail. The management of each type of complication is outlined, including the
      use of computed tomography and magnetic resonance imaging, and the role of
      surgical drainage.

PMID- 7643280
TI  - The oral surgical operations of Grover Cleveland: a presidential cover-up.

PMID- 7643281
TI  - Glucocorticoid therapy for myasthenia gravis resulting in resorption of the
      mandibular condyles.

PMID- 7643282
TI  - Gastric carcinoma metastatic to the mucosa of the hard palate.

PMID- 7643283
TI  - Post-traumatic cranial mucormycosis in an immunocompetent patient.

PMID- 7643285
TI  - Spread of squamous cell carcinoma of the lower lip along the inferior alveolar
      nerve: a case report.

PMID- 7643284
TI  - Intraoperative life-threatening emphysema associated with endotracheal intubation
      and air insufflation devices: report of two cases.
AB  - Two cases of life-threatening body emphysema with decompensating pneumothoraces,
      pneumomediastinum, and pneumopericardium intraoperatively have been presented.
      The most likely cause was tracheal perforation combined with high pressure
      ventilation. Although subcutaneous emphysema and pneumomediastinum are self
      limiting conditions with rapid recovery with conservative treatment, life
      threatening complications may arise requiring prompt recognition and specific
      surgical management in order to save the patient's life.

PMID- 7643286
TI  - Oral histoplasmosis masquerading as an invasive carcinoma.

PMID- 7643287
TI  - Fibro-odontogenic dysplasia: report of two familial cases.

PMID- 7643289
TI  - Contributing to the future of oral and maxillofacial surgery.

PMID- 7643288
TI  - The masking of orthognathic problems.

PMID- 7643290
TI  - Evaluation of temporomandibular joint prostheses: review of the literature from
      1946 to 1994 and implications for future prosthesis designs.
AB  - PURPOSE: This article describes the useful elements of applied temporomandibular
      joint (TMJ) prostheses and discusses the factors necessary to be addressed in an
      appropriate TMJ prostheses design. MATERIALS AND METHODS: Information about TMJ
      prostheses was gathered by a literature search. Only designs with the primary
      intention of true joint replacement were selected. The designs were divided in
      fossa-eminence, condylar, and total joint replacements, which are reviewed
      separately. RESULTS: A fossa-eminence prosthesis can be fixed by a metal plate
      screwed to the root of the zygomatic arch. A condylar prosthesis can be fixed by
      a metal plate screwed to the mandibular ramus and fitted by bending the plate or
      using different sizes. All reviewed designs resulted in a loss of translational
      movements of the mandible, especially in an anterior direction. Although the
      recent designs use the same materials as are used in hip and knee joint
      prostheses, the wear properties of the existing TMJ prostheses are still unknown.
      CONCLUSIONS: A future prosthesis must imitate the anterior movement of the
      mandible when the mouth is opened and also allow some mediolateral movement. The
      fitting to the skull is still a major problem, as is the combination of the
      required motions and low wear rates. To confirm good clinical performance of a
      new TMJ prosthesis, long-term follow-up studies are necessary.

PMID- 7643291
TI  - Full-thickness skin grafting of postsurgical oral defects: short- and long-term
      outcomes.
AB  - PURPOSE: This study evaluated the use of full-thickness skin grafts (FTSGs)
      following excision of precancerous and cancerous oral lesions. MATERIALS AND
      METHODS: Fourteen oral lesions, including five leukoplakias, one carcinoma in
      situ, two verrucous carcinomas, and six squamous cell carcinomas with varying
      grade of keratinization and invasion were skin grafted after excision. The size
      of the graft ranged from 16 x 22 mm to 40 x 50 mm, and the fixation period was 8
      to 13 days. The grafts were evaluated for necrosis as a short-term result and
      shrinkage and recurrence of the lesion as long-term results. RESULTS: Three cases
      with more than moderate necrosis of the grafted skin were observed (21.4%).
      Shrinkage was observed in 23% of the 14 skin grafts and tumor recurrence was
      observed in three FTSGs (2 patients). CONCLUSIONS: The results suggest that the
      paucity of the blood supply in the grafted bed, and the uneven pressure and
      immobilization of the grafted skin, influence the success of the procedure, and
      that proper case selection is necessary.

PMID- 7643292
TI  - Dielectric properties of grapes and sugar solutions at 2.45 GHz.
AB  - Dielectric properties of grapes at 2.45 GHz were measured at moisture contents
      varying from 80 to 15% (wet basis) at temperatures ranging from 25-80 degrees C
      using the Open Ended Coaxial Transmission Line Technique. Both dielectric
      constant and loss factor decreased with decreasing moisture content. In low
      moisture samples these properties were found to be considerably influenced by
      higher temperatures. Dielectric properties of sugar solutions of varying
      concentrations (20-250% by weight in water) were also determined at different
      temperatures, and these values were compared to those of grapes of corresponding
      moisture concentration. Predictive models of the dieletric properties as
      functions of moisture content and temperature were generated using response
      surface methodology. The results are useful in estimating the volumetric heating
      of grapes by microwave energy, and these methods can be extended to sugar-based
      foods in general.

PMID- 7643293
TI  - Extending the storage life of chilled beef: microwave processing.
AB  - This study investigates whether it is possible to use microwave technology to
      reduce the bacterial load of meat to such an extent that shelf-life is extended
      while the product retains the appearance of fresh meat. It investigates the use
      of microwaves in raising the surface temperature of vacuum-packed beef steak,
      recording the total aerobic and anaerobic bacterial count, the appearance of the
      meat and the amount of purging of meat juices within the package.

PMID- 7643294
TI  - Harter's Self-Perception Profile for Adolescents: reliability, validity, and
      evaluation of the question format.
AB  - The Self-Perception Profile for Adolescents (SPPA; Harter, 1988) was administered
      to a national representative sample of 11,315 Norwegian adolescents of the ages
      13 to 20. The original version of SPPA has an idiosyncratic and time-consuming
      item format, describing two adolescents with opposite characteristics on each
      item. A revised version of SPPA was developed using only one statement for each
      item. The original SPPA was administered to a random subsample of 880 subjects,
      whereas the rest of the total sample completed the revised edition. Concerning
      the original SPPA, results showed low to adequate reliability and poor
      replication of the factorial pattern. However, low correlations with the Marlowe
      Crowne Social Desirability Index were obtained, and the construct validity was
      supported. Concerning the revised edition, the a priori factorial pattern was
      replicated. Further, it had substantially better reliability, better convergent
      validity, and better factorial validity than the original version. The
      discriminant validity and the contamination by social desirability bias were the
      same for both versions. The data thus indicate that there is no need to retain
      the time-consuming and cumbersome item format of the original SPPA.

PMID- 7643295
TI  - The convergence of the California Q-set and the California Psychological
      Inventory: gender as a critical variable.
AB  - Clinician-report California Q-set and self-report California Psychological
      Inventory data were compared to explore convergence and divergence between these
      two modes of personality assessment. Based on responses from a sample of 215
      approximately 50-year-old men and women, the self-report California Psychological
      Inventory data were converted to California Q-set item values using previously
      determined redundancy analysis formulae. These data were then correlated with
      composite clinicians' ratings, using the same California Q-set items. Substantial
      convergence was found for both genders on four of six derived components-
      Empowerment, Intellectuality, Nonconformity, and Outgoingness. Two additional
      components--Psychological Health and Bodily Concern--showed convergence for women
      only. We argue analysis of item content and scores must be done for each gender
      separately.

PMID- 7643296
TI  - PAI profiles in alcohol-dependent patients.
AB  - This study examined the use of a recently developed inventory, the Personality
      Assessment Inventory (PAI; Morey, 1991), in developing a typology of alcoholic
      types. Clustering procedures were applied to the PAI clinical scale profiles of a
      group (N = 301) of alcohol-dependent patients. Seven cluster profiles were
      identified: Depressed, Antisocial Acts, Personality Disorder, Dysphoric, Somatic
      Concerns, Normal, and Distressed. Examination of nonclinical PAI scales and
      several external variables revealed support for the validity of the seven profile
      types. Results were compared to cluster analysis findings from other inventories
      with this population.

PMID- 7643297
TI  - Spontaneous self-descriptions and ethnic identities in individualistic and
      collectivistic cultures.
AB  - The Twenty Statements Test (TST) was administered in Seoul and New York, to 454
      students from 2 cultures that emphasize collectivism and individualism,
      respectively. Responses, coded into 33 categories, were classified as either
      abstract or specific and as either autonomous or social. These 2 dichotomies were
      more independent in Seoul than in New York. The New York sample included Asian
      American whose spontaneous social identities differed. They either never listed
      ethnicity-nationality on the TST, or listed it once or twice. Unidentified Asian
      Americans' self-concepts resembled Euro-Americans' self-concepts, and twice
      identified Asian Americans' self-concepts resembled Koreans' self-concepts, in
      both abstractness-specificity and autonomy-sociality. Differential acculturation
      did not account for these results. Implications for social identity, self
      categorization, and acculturation theory are discussed.

PMID- 7643298
TI  - Effects of introspecting about reasons: inferring attitudes from accessible
      thoughts.
AB  - Previous research has shown that analyzing reasons can change people's attitudes,
      but the exact mechanisms of this effect have not been entirely clear. It was
      hypothesized that introspecting about reasons focuses people's attention on
      thoughts that are accessible in memory and increases the extent to which people
      view their accessible thoughts as applicable to their current attitudes. In Study
      1, college students formed initial impressions of a target person, and then
      positive or negative thoughts about the target person were made memorable. After
      a delay, half of the participants analyzed reasons for their attitude and half
      recalled the target person's behaviors. As predicted, people who analyzed reasons
      reported attitudes toward the target person that were based more on what they
      could recall about her. Study 2 showed that this effect occurs regardless of
      whether people initially form an online impression. Implications for the effects
      of analyzing reasons and for attitude formation are discussed.

PMID- 7643299
TI  - Effects of self-focused rumination on negative thinking and interpersonal problem
      solving.
AB  - Hypotheses about the effects of self-focused rumination on interpretations of
      events and interpersonal problem solving were tested in 3 studies with dysphoric
      and nondysphoric participants. Study 1 supported the hypothesis that dysphoric
      participants induced to ruminatively self-focus on their feelings and personal
      characteristics would endorse more negative, biased interpretations of
      hypothetical situations than dysphoric participants induced to distract
      themselves from their mood, or nondysphoric participants. Study 2 showed that
      dysphoric participants who ruminated were more pessimistic about positive events
      in their future than the other 3 groups. Study 3 showed that dysphoric ruminating
      participants generated less effective solutions to interpersonal problems than
      the other 3 groups. In Studies 1 and 3, dysphoric ruminating participants also
      offered the most pessimistic explanations for interpersonal problems and
      hypothetical negative events. In all 3 studies, dysphoric participants who
      distracted were as optimistic and effective in solving problems as non-dysphoric
      participants.

PMID- 7643300
TI  - Similarity in married couples: a longitudinal study of mental abilities and
      rigidity-flexibility.
AB  - Longitudinal changes in couple similarity on the Primary Mental Abilities and the
      Test of Behavioral Rigidity were studied over 7-year intervals from 1956 to 1984
      in 169 couples from the Seattle Longitudinal Study. Positive, initial intraclass
      spousal correlations were significant for verbal meaning, inductive reasoning,
      word fluency, educational aptitude, intellectual aptitude, attitudinal
      flexibility, psychomotor speed, and social responsibility, as well as age and
      education. After age and education had been controlled, significant increases in
      spousal similarity were found for verbal meaning and intellectual ability over 14
      years and for attitudinal flexibility over 21 years. The higher functioning
      spouses' word fluency influenced the lower functioning spouses' verbal meaning
      and word fluency over time. Couples who became more similar over time involved
      husbands in higher occupations and wives with fewer changes in profession.

PMID- 7643301
TI  - Transference in social perception: the role of chronic accessibility in
      significant-other representations.
AB  - Research has shown that the activation and application of a significant-other
      representation to a new person, or transference, occurs in everyday social
      perception (S. M. Andersen & A. Baum, 1994; S. M. Andersen & S. W. Cole, 1990).
      Using a combined idiographic and nomothetic experimental paradigm, two studies
      examined the role of chronic accessibility of significant-other representations
      in transference. After learning about 4 fictional people, 1 of whom resembled a
      significant other, participants' recognition memory was assessed. Both studies
      showed greater false-positive memory in the significant-other condition, relative
      to control, even in the absence of priming. Study 2 showed that although the
      effect was greater when the significant-other representation was concretely
      applicable to the target information, it occurred even when no such applicability
      was present. Results implicate the chronic accessibility of significant-other
      representations in transference.

PMID- 7643302
TI  - Positive mood can increase or decrease message scrutiny: the hedonic contingency
      view of mood and message processing.
AB  - Currently dominant explanations of mood effects on persuasive message processing
      (i.e., cognitive capacity and feelings as information) predict that happy moods
      lead to less message scrutiny than neutral or sad moods. The hedonic contingency
      view (D. T. Wegener & R. E. Petty, 1994) predicts that happy moods can sometimes
      be associated with greater message processing activity because people in a happy
      mood are more attentive than neutral or sad people to the hedonic consequences of
      their actions. Consistent with this view, Experiment 1 finds that a happy mood
      can lead to greater message scrutiny than a neutral mood when the message is not
      mood threatening. Experiment 2 finds that a happy mood leads to greater message
      scrutiny than a sad mood when an uplifting message is encountered, but to less
      message scrutiny when a depressing message is encountered.

PMID- 7643303
TI  - Effects of mindset on positive illusions.
AB  - S. E. Taylor and J. D. Brown's (1988) position that mentally healthy people
      exhibit positive illusions raises a dilemma: How do people function effectively
      if their perceptions are positively biased? Using Gollwitzer's deliberative
      implemental mindset distinctiion, we assessed whether people in a deliberative
      mindset show less evidence of positive illusions than people in an implemental
      mindset. Participants completed a mindset task and assessments of mood, self
      perceptions, and perceived (in)vulnerability to risk. Deliberation led to
      worsened mood, greater perceived risk, and poorer self-perceptions, relative to
      implementation; control (no mindset) participants typically scored in between.
      Study 3 demonstrated that the mindset manipulation corresponds to how people
      actually make decisions or implement them. Results suggest that people use
      relatively realistic thinking when setting goals and more positive thinking when
      implementing them.

PMID- 7643304
TI  - When comparisons arise.
AB  - People acquire information about their abilities by comparison, and research
      suggests that people restrict such comparisons to those whom they consider
      sources of diagnostic information. We suggest that diagnosticity is often
      considered only after comparisons are made and that people do not fail to make
      nondiagnostic comparisons so much as they mentally undo them. In 2 studies,
      participants made nondiagnostic comparisons even when they knew they should not,
      and quickly unmade them when they were able. These results suggest that social
      comparisons may be relatively spontaneous, effortless, and unintentional
      reactions to the performances of others and that they may occur even when people
      consider such reactions logically inappropriate.

PMID- 7643305
TI  - Individual-group behavioral similarity and peer status in experimental play
      groups of boys: the social misfit revisited.
AB  - This study evaluated individual-group similarity and dissimilarity hypotheses
      generally stipulating that the behavioral correlates of status are moderated by
      the peer group context in which they are displayed. Thirty play groups of 5 or 6
      unacquainted same-age boys participated in five 45-min sessions. Five behaviors
      described group and individual characteristics: reactive aggression, proactive
      aggression, solitary play, rough-and-tumble play, and positive interactive
      behavior. Individual social preference scores were computed following a variant
      of the J. D. Coie and K. A. Dodge (1983) procedure. The behavioral correlates of
      emerging peer status were examined as a function of the group's behavioral norms.
      Evidence of a dissimilarity effect was found for solitary play and reactive
      aggression whereas positive interactive behavior followed a rule of similarity.

PMID- 7643306
TI  - Concordance in the face of a stressful event: when do members of a dyad agree
      that one person supported the other?
AB  - Students reported behaviors they expected from a primary support persons in
      response to an upcoming exam. After the exam, students and support persons
      independently reported behaviors the supporter provided. There was only moderate
      agreement within dyads about the occurrence of supportive behaviors (kappa =
      .39). Dyad intimacy, fulfilled expectancies, student and supporter social
      competence, and commal orientation all were associated with greater concordance.
      There was also greater agreement on behaviors rated by judges as helpful than
      harmful and in dyads that included a woman than in man-man dyads. Greater dyad
      intimacy and more fulfilled expectancies accounted for why there was greater
      concordance in dyads that included a women, and more fulfilled expectancies
      accounted for why there was greater concordance on positive than negative
      behaviors.

PMID- 7643307
TI  - Primary traits of Eysenck's P-E-N system: three- and five-factor solutions.
AB  - The Eysenck Personality Profiler (EPP), a set of 21 scales measuring primary
      traits hypothesized to be definers of Neuroticism, Extraversion, and Psychoticism
      factors, was administered to 229 adults together with the Eysenck Personality
      Questionnaire--Revised (H. J. Eysenck & S. B. G. Eysenck, 1991) and the Revised
      NEO Personality Inventory (NEO-PI-R; P. T. Costa & R. R. McCrae, 1992b).
      Correlations of EPP scales with NEO-PI-R facet scales provided preliminary
      evidence supporting the convergent and discriminant validity of the EPP scales.
      However, varimax and targeted validimax factor analyses suggested that some EPP
      scales were misclassified and that EPP scales could better be understood in terms
      of the 5-factor model than the intended 3-factor model.

PMID- 7643308
TI  - To whom do people turn when things go poorly? Task orientation and functional
      social contacts.
AB  - Using experience-sampling data the authors examined distinct benefits and uses of
      social support. As expected, emotional support buffered negative psychological
      states, and informational support appeared to facilitate mastery-related states,
      among individuals who had previously reported low well-being. An examination of
      social pursuits revealed that these distinct kinds of support were sought by
      individuals who were especially likely to need them. Participants focused on
      outcomes in their social lives, and therefore especially likely to be emotionally
      distressed when social pursuits go poorly, responded to poor social well-being by
      spending time with emotional supporters. Participants focused on improvement in
      their social lives responded to poor social well-being by spending time with
      others who could provide information to facilitate self-improvement--people who
      personified their self-ideals.

PMID- 7643309
TI  - Using the confluence model of sexual aggression to predict men's conflict with
      women: a 10-year follow-up study.
AB  - We tested a model describing the characteristics of sexually aggressive men that
      may also be useful for understanding the causes of other antisocial acts against
      women. This model hypothesizes that sexual aggressors can be identified by two
      sets of characteristics, labeled hostile masculinity and impersonal sex. To test
      this model, we followed up a sample of men 10 years after first studying them
      when they were young adults. We sought to predict which men would be in
      distressed relationships with women, be aggressive sexually, be nonsexually
      aggressive, or some combination of these. These behaviors were measured not only
      by questioning the men themselves but also by questioning many of the men's
      female partners. Some couples' videotaped conversations were also analyzed. The
      data supported the ability of the model to predict behavior 10 years later. We
      also developed the model further and identified the common and unique
      characteristics contributing to sexual aggression as compared with the other
      conflictual behaviors studied. The data supported the usefulness of hierarchical
      modeling incorporating both general factors that contribute to various
      interpersonal conflicts as well as specific factors uniquely pertaining to
      dominance of women.

PMID- 7643310
TI  - A test of the cognitive diathesis-stress model of depression in children:
      academic stressors, attributional style, perceived competence, and control.
AB  - The cognitive diathesis-stress model of depression was tested in a sample of 439
      children in grades 5 and 6. Attributional style and cognitions about academic
      competence and control over achievement were assessed before the occurrence of a
      potentially stressful event--receiving unacceptable grades on a report card.
      Depressive symptoms were assessed 1 week before the event, the morning after, and
      5 days later. Replicating G. I. Metalsky, L. J. Halberstadt, and L. Y. Abramson
      (1987), stressor level and negative cognitions predicted depressive symptoms the
      morning after the event, controlling for initial symptom levels. Depressive
      symptoms 5 days later were predicted by the interactions of negative cognitions
      with stressors, supporting a cognitive diathesis-stress model. Students who
      reported a negative explanatory style or lack of academic control and competence
      expressed more distress after receiving unacceptable grades than did students
      without such cognitions.

PMID- 7643311
TI  - Accumulation of problems in social functioning in young adulthood: a
      developmental approach.
AB  - Using longitudinal data from a sample of 369 Finnish adolescents, the authors
      examined whether problems in social functioning in young adulthood were
      interrelated and accumulated, and analyzed processes that may lead to cumulative
      problems. The log-linear modeling showed that an unstable career line of men at
      age 26 was related to poor social relations, a poor financial standing, drinking
      problems, and criminal arrests; for both sexes, drinking problems and criminal
      arrests were interrelated. At a personal level, the authors analyzed male
      patterns of problems in social functioning and pathways resulting in patterns of
      social functioning. The pathway leading to an unstable career, criminal arrests,
      and drinking problems among men included aggressiveness at age 8 and problems in
      school adjustment and in the family at age 14.

PMID- 7643312
TI  - AIDS and HIV-related topics. Part I. Introduction.

PMID- 7643313
TI  - History and epidemiology of acquired immune deficiency syndrome.
AB  - Acquired immune deficiency syndrome (AIDS) and human immunodeficiency virus (HIV)
      were first noticed in the US in 1981 and continue to spread today. Initially a
      disease associated completely with homosexual males, it is increasing in
      incidence and prevalence among heterosexual males and females, particularly, but
      not limited to, injection drug users. This disease is much more prevalent among
      blacks and Hispanics. Podiatric physicians are at risk of acquiring the disease
      as a result of their frequent use of injections and surgical intervention,
      particularly involving bone. In addition, the foot is a potential portal of entry
      for HIV infection because of contamination by blood on the feet of podiatric
      surgeons and their assistants during surgery.

PMID- 7643314
TI  - Neurologic conditions affecting the lower extremities in HIV infection.
AB  - The vast majority of patients with human immunodeficiency virus (HIV) and
      acquired immune deficiency syndrome (AIDS) have symptoms or signs involving the
      feet and lower extremities. Patients presenting to podiatrists with foot
      complaints may, in fact, have neurologic complications of HIV originating in any
      level of the neuraxis, and multiple levels may be involved. These include
      multiple classes of peripheral neuropathy and myopathy, inflammatory
      radiculopathy, myelopathy, and central nervous system lesions caused by direct
      HIV infection or opportunistic infections. Common complaints such as pain,
      numbness, burning, tingling, weakness, cramps, unsteady gait, and others should
      be systematically evaluated with both podiatric and neurologic etiologies in mind
      for early diagnosis and intervention.

PMID- 7643315
TI  - Cutaneous manifestations of HIV-1 infection.
AB  - Infection with the human immunodeficiency virus (HIV) leads to a chronic
      disarmament of the immune system. The process is progressive, having different
      manifestations as the status of the immune system slowly deteriorates. Some of
      the most common manifestations of HIV infection are cutaneous in origin, and they
      can have infectious, neoplastic, or noninfectious or non-neoplastic etiologies. A
      brief history of HIV is given, and the most common cutaneous presentations of the
      virus infection of interest to podiatrists are outlined.

PMID- 7643316
TI  - Guide to medications used to treat acquired immune deficiency syndrome.
AB  - Currently, there is no means to eradicate the human immunodeficiency virus (HIV)
      from the human body. Thus, drug therapy provides an important mechanism to slow
      viral replication and its damaging effects on the body. A review of the drugs
      used in the care of the patient with acquired immune deficiency syndrome (AIDS)
      is provided, which highlights the significant adverse reactions and interactions
      associated with their use.

PMID- 7643317
TI  - Rehabilitation management of the lower extremity in HIV disease.
AB  - The sequelae of human immunodeficiency virus (HIV) disease include a host of
      devastating conditions involving the lower extremity. These include rheumatologic
      dysfunction, Kaposi's sarcoma, peripheral neuropathies, and skin ulcers. Pain,
      weakness, and loss of range of motion caused by these conditions can lead to
      changes in gait pattern, loss of mobility and function, and limited quality of
      life. The role of the rehabilitation specialist in the care and treatment of HIV
      disease as it affects the lower extremity, and the treatment strategies,
      precautions, and suggestions will be discussed.

PMID- 7643318
TI  - [Analysis of data from single-channel recording].

PMID- 7643319
TI  - Daily and circadian variation in the electroretinogram of the domestic fowl:
      effects of melatonin.
AB  - Visual and circadian function are integrally related in birds, but the precise
      nature of their interaction is unknown. The present study determined whether
      visual sensitivity measured electroretinographically (ERG) in 7-week-old
      cockerels varies over the time of day, whether this rhythm persists in constant
      darkness (DD) and whether exogenous melatonin affects this ERG rhythmicity. ERG b
      wave amplitude was rhythmic in LD and persisted in DD with peak amplitude during
      mid- to late afternoon in LD and mid-subjective day in DD, indicating that the
      ERG rhythm is endogenously generated. No daily or circadian variation in a-wave
      amplitude was observed, and ERG component latency and durations were not
      rhythmic. Intramuscular injection of 10 micrograms/kg melatonin at ZT10 in LD
      significantly decreased b-wave amplitude but had no effect on a-wave. Intraocular
      injection of 600 pg melatonin, however, had no effect on any aspect of the ERG.
      These data indicate that a circadian clock regulates ocular sensitivity to light
      and that melatonin may mediate some or all of this effect. The level at which
      melatonin modulates retinal sensitivity is not known, but the present data
      suggest a central site rather than a direct effect of the hormone in the eye.

PMID- 7643320
TI  - Coordination and neuromuscular control of rhythmic behaviors in the blue crab,
      Callinectes sapidus.
AB  - The stereotypical courtship display (CD) behavior of the male blue crab,
      Callinectes sapidus, includes an unusual component: the rhythmic waving of the
      swimming appendages above the carapace. This behavior occurs in a unique context
      but it resembles two other rhythmic behaviors performed using the swimming legs:
      sideways swimming and backward swimming. As a first step to understanding the
      mechanisms that allow the expression of apparently different rhythmic motor
      patterns, we have examined these behaviors using slow motion video analysis and
      electromyography of the basal muscles of the swimming legs in freely behaving
      crabs. The results show that these behaviors are distinguished by four
      parameters: the frequency of leg waving, the phase relationship between the legs,
      the presence of a stationary pause in basal muscle activity combined with
      rotation of the distal leg during CD, and an extended range of motion of these
      legs during CD and backward swimming, relative to sideways swimming. EMG analysis
      revealed that during sideways swimming, the sequence of muscular activity between
      the two legs was different. In contrast, during CD and backward swimming the
      sequence of activity for these legs is identical.

PMID- 7643321
TI  - Modulation of behavior by biogenic amines and peptides in the blue crab,
      Callinectes sapidus.
AB  - Using the blue crab Callinectes sapidus as a model system, we have investigated
      the effects of potential neuromodulators on freely behaving animals. Of interest
      is the modulatory effect of a number of drugs on three rhythmic behaviors of the
      blue crab: courtship display (CD) of the male crab, sideways swimming and
      backward swimming. The drugs tested were proctolin, dopamine, octopamine,
      serotonin, and norepinephrine. Injection of each drug elicited a unique posture
      or combination of limb movements. These experiments showed two results pertinent
      to CD behavior: A posture identical to the CD posture was displayed after
      dopamine injection; and rhythmic leg waving similar to CD was evoked by
      proctolin. An unusual combination of flexion and extension of all limbs and
      movements of some limbs occurred after serotonin injection. Injection of
      octopamine led to a posture antagonistic to CD posture. The effects of these
      drugs were concentration- and time-dependent. Injection of dopamine, octopamine,
      or serotonin produced effects that were seasonally-dependent, and the influence
      of proctolin proved to be dependent on developmental stage. Quantitative analysis
      of leg waving movements after proctolin injection allowed for comparison of these
      movements to naturally-occurring behavior.

PMID- 7643322
TI  - Neuromodulation of rhythmic motor patterns in the blue crab Callinectes sapidus
      by amines and the peptide proctolin.
AB  - The blue crab Callinectes sapidus, provides an opportunity to study
      neuromodulation of three variations of rhythmic behavior produced by the same
      appendages. These behaviors are sideways swimming, backward swimming and
      courtship display (CD). Each behavior has a different context, and despite
      similarities among them, each is quantifiably distinguishable. CD behavior occurs
      in males, is stimulated naturally by pheromone, and elements of the behavior are
      evoked by proctolin and dopamine. Sideways and backward swimming do not share
      these characteristics. Bath-applied proctolin, combined with either electrical or
      pheromonal stimulation, was used to search for interneurons influencing motor
      outflows from the fifth legs. Interneurons were found which, when stimulated
      electrically, initiated rhythmic behavior. At least one of these neurons
      responded to pheromonal stimulation. Application of proctolin combined with
      stimulation of descending 'trigger' cells resulted in changes from a backward
      swimming motor pattern toward a CD pattern. Dopamine applied with proctolin
      lowered the concentration threshold for proctolin-evoked changes in motor
      outflows. Octopamine co-applied with proctolin extinguished the proctolin effect
      unless dopamine was co-applied. Combinations of modulators appear to play
      critical roles in shaping patterns of rhythmic motor activity of the fifth legs.

PMID- 7643323
TI  - Remarks by Herschel S. Horowitz upon receiving the 1994 John W. Knutson
      distinguished Service Award in Dental Public Health.

PMID- 7643324
TI  - President's welcome and address.

PMID- 7643325
TI  - President's Award: Stephen B. Corbin.

PMID- 7643326
TI  - 1994 Special Merit Award: John Scott Small.

PMID- 7643328
TI  - 1994 Distinguished Service Award: Martha L. Liggett.

PMID- 7643327
TI  - 1994 Special Merit Award: Jay W. Friedman, DDS, MPH.

PMID- 7643329
TI  - Preservative dentistry: the standard of care for the 21st century.

PMID- 7643330
TI  - Three-year root caries incidence and risk modeling in older adults in North
      Carolina.
AB  - OBJECTIVES: The purposes of this study were to describe the incidence of root
      caries and to identify its risk factors in a representative sample of older
      adults. METHODS: Root caries incidence was estimated and multivariate risk
      assessment models were developed to identify predictors for root caries in a
      three-year follow-up study of 234 black and 218 white noninstitutionalized adults
      aged 65 and older residing in North Carolina. RESULTS: During the observation
      period, 29 percent of blacks developed root caries, compared to 39 percent of
      whites (P < .05). The mean net DFS increment per person was 0.55 +/- 0.13 root
      surfaces for blacks vs 0.80 +/- 0.21 for whites (P > .32). Multivariate logistic
      regression analysis indicated that blacks wearing a partial denture, having some
      root fragments, having an average gingival recession > or = 2 mm, and being free
      of P. intermedia were at greater risk for developing new root caries. The model
      for whites showed that retired people with their most severe gingival recession >
      or = 4 mm, an average probing pocket depth > or = 2 mm, and taking antihistamines
      were more likely to develop new lesions. CONCLUSIONS: These findings suggest that
      older blacks had less risk of root caries than whites, and in both groups
      indicators of poor periodontal status increased the risk of root caries.

PMID- 7643331
TI  - Dental fluorosis and caries prevalence in children residing in communities with
      different levels of fluoride in the water.
AB  - OBJECTIVES: This study investigated the prevalence of dental fluorosis and caries
      in 7-14-year-old children residing in communities with negligible (NF: 0.2 ppm),
      optimal (OPF: 1.0 ppm), and four-times optimal (4X OPF: 4.0 ppm) naturally
      occurring fluoride in their water systems. METHODS: Examinations were performed
      on 344 children who were lifetime residents of their communities. RESULTS:
      Whether using the tooth surface index of fluorosis or Dean's index, children
      examined in the 4X OPF community had the highest prevalence of dental fluorosis.
      While the severity of fluorosis seen in the OPF and NF communities was mild in
      appearance, the results indicate that fluorosis does occur in optimally and
      negligibly fluoridated communities. Compared to the NF community, DMFT and DMFS
      scores in the OPF community were 9.2 percent and 21.2 percent lower,
      respectively. CONCLUSIONS: The ingestion of water containing 1 ppm or less
      fluoride during the time of tooth development may result in dental fluorosis,
      albeit in its milder forms. However, in these times of numerous products
      containing fluoride being available, children ingesting water containing 1 ppm
      fluoride continue to derive caries protection compared to children ingesting
      water with negligible amounts of fluoride. Thus, the potential for developing a
      relatively minor unesthetic condition must be weighed against the potential for
      reducing dental disease.

PMID- 7643333
TI  - The John W. Knutson Distinguished Service Award in Dental Public Health--1994
      recipient: Herschel S. Horowitz.

PMID- 7643332
TI  - Prevalence of dental caries and dental fluorosis in areas with optimal and above
      optimal water fluoride concentrations: a 10-year follow-up survey.
AB  - OBJECTIVES: This paper presents findings for dental caries and fluorosis from an
      October 1990 follow-up survey in Illinois and compares results with those
      obtained from two similar school-based examinations conducted in 1980 and 1985
      within the same communities. METHODS: The seven study sites were grouped into
      four categories according to the approximate relation of their water fluoride
      concentration to the recommended optimal fluoride level for the area. Tests for
      differences in dental caries and dental fluorosis across the four water fluoride
      groupings and three examinations were conducted. RESULTS: DMFS scores for
      children who resided in communities with above-optimal water fluoride levels did
      not change significantly from 1980 through 1990. At the optimal water fluoride
      concentration, caries scores did not change substantially from 1980 to 1985;
      however, the mean DMFS score in 1990, 1.9, was significantly lower than caries
      levels observed during the two previous exams. In the optimally fluoridated area,
      the proportion of fluorosed tooth surfaces increased significantly from 1980 to
      1985, but then declined by 1990 to the level observed in 1980 for both age
      groups. CONCLUSIONS: The results suggest that: (1) in the optimally fluoridated
      community, the apparent increase in the prevalence of dental fluorosis observed
      from 1980 to 1985 did not continue from 1985 to 1990; and (2) at above-optimal
      water fluoride concentrations, dental fluorosis either remained stable or
      demonstrated no sustained increase over the decade.

PMID- 7643334
TI  - Hersh's so-called life: from a (slightly) biased perspective.

PMID- 7643335
TI  - Comments made at the presentation of the John W. Knutson Distinguished Service
      Award in Dental Public Health to Herschel S. Horowitz, DDS, MPH.

PMID- 7643336
TI  - Teenagers swap pill for condom.

PMID- 7643338
TI  - CDM/CONDAM. The Construction (Design and Management) Regulations 1994.

PMID- 7643337
TI  - Stroke care in Europe. Can we learn lessons from the different ways stroke is
      managed in different countries?
AB  - Stroke is a major health care problem in the European Union and consumes
      significant resources. The mortality rates from stroke and treatment strategies
      vary significantly between member states. Only by comparison between centres in
      different member states with differing health care delivery can the effect of
      these varying approaches to the management of stroke on outcome be assessed.
      Conducting a study on a European wide basis in centres which are known to differ
      in terms of treatment strategies and outcomes allows an immediate analysis of the
      effectiveness, resource requirements and cost of different methods of managing
      stroke patients. This paper addresses the current burden of stroke and strategies
      for its management. An outline of a European Union project, assessing how stroke
      is managed in different countries, is provided with the aim of indicating a
      strategy for discovering and promoting more cost-effective services for stroke
      care in the future.

PMID- 7643339
TI  - Aid programmes in eastern Europe. Can we learn from Third World experience?

PMID- 7643340
TI  - Children's smoking: the shopkeepers' perspective.
AB  - A self-administered postal questionnaire was sent to 216 Bolton shopkeepers to
      examine their knowledge and attitudes about children's smoking. The response rate
      was 76%. A majority of respondents (57%) were in favour of banning cigarette
      advertising; this option was supported by significantly more women (73%) than men
      (46%), (p < 0.05). There was widespread recognition of the harmful consequences
      of children's smoking (97%), although the highly addictive nature of cigarettes
      was not as widely acknowledged (41%). Many of the shopkeepers perceived
      children's smoking as a normal part of growing up (49%); this view was held more
      frequently by shopkeepers who had smoked during their own childhood (62%).
      Challenging shopkeepers' acceptance of children's smoking as a normal part of
      growing up, and increasing their awareness about the highly addictive nature of
      cigarettes, may reduce their willingness to sell cigarettes to children.

PMID- 7643341
TI  - Sickle cell anaemia in Saudi-Arabian children.
AB  - Forty-one Saudi Arabian children aged between six months and 13 years had a total
      of 68 admissions for complications of sickle cell anaemia during 1992. Review of
      their in-patient records and the relevant out-patient notes revealed a change in
      the clinical profile as compared to previous years. Hand-foot syndrome is
      virtually non-existent and vaso-occlusive crisis remains the commonest cause of
      admission. Introduction of pneumococcal vaccine and prophylactic oral penicillin
      has had no effect on the frequency of admissions and the admission rate per
      patient year. We have not seen any septicaemia/meningitis due to pneumococci. No
      death occurred during 1992.

PMID- 7643342
TI  - The growth pattern of Kuwaiti pre-school children. Compared to NCHS/CDC reference
      population.
AB  - The aim of this study was to present growth charts of pre-school children based
      on cross-sectional data of the population in Kuwait to determine their health
      status. This survey was carried out during September 1989 to June 1990. The
      growth patterns of weight and heights per age were designed separately for boys
      and girls. The growth pattern of height for age, and weight by age were
      constructed and smoothed by the spline regression polynomial technique. The girls
      were taller than the boys after the age of one year. The growth deficit in
      children from Kuwait compared with internationally recommended reference
      populations may be attributed to genetic and environmental factors. The growth
      pattern presented here will suffice as a standard in monitoring the growth of
      Kuwaiti children in particular and those in the Gulf region in general.

PMID- 7643343
TI  - Severity signs of childhood diarrhoea in north eastern Nigeria.
AB  - Oral Rehydration Therapy (ORT) use in Nigeria is currently far short of the
      national Control of Diarrhoeal Diseases (CDD) programme goals. Towards designing
      health education strategies to improve this, maternal lay health concerns during
      diarrhoea in under-fives were examined among two large ethnic groups, the Kanuris
      and Buras, in northeastern Nigeria. Over half of the respondents judged the
      severity of diarrhoea by more than one sign and expected ORT to stop diarrhoea.
      Severity signs frequently described (averaging from a quarter to a half of
      respondents) included weakness and refusal of food; frequent stooling and fever
      were more frequently used by the Kanuris (p < 0.001) compared to Buras and weight
      loss and dehydration by the Buras (p < 0.01) compared to Kanuris. Generally,
      rural residents were less concerned with dehydration and weight loss (p < 0.0001
      and 0.003 respectively, compared to urban residents) and more concerned with
      restlessness, including excessive crying (p < 0.07 to 0.0001). Stool
      characteristics and vomiting were rarely used as severity signs although the
      Kanuris in focus group discussions related severity to diarrhoea typology.
      Concerns with persistent diarrhoea, and diarrhoea associated with measles, were
      rarely expressed by participants, irrespective of ethnic group and domicile,
      suggesting that health education aimed at increasing awareness in relation to
      these two serious illnesses is urgently needed in Nigeria. Several of the lay
      health concerns expressed by participants in the study could form a useful basis
      for promoting ORT use in Nigeria and elsewhere.

PMID- 7643345
TI  - Food-borne parasitoses in Malaysia epidemiological assessment and research needs.
AB  - Food-borne parasitic zoonoses have emerged as a major public health problem in
      many countries and are posing a medical challenge. They are not only important
      from the economic point of view but also because of their severe sequelae. In
      Malaysia, these parasitoses are a tip of an iceberg problem. The article
      documents all the food-borne parasitic zoonoses reported in Malaysia. An
      epidemiological assessment of the diseases with research needs is highlighted.

PMID- 7643344
TI  - A code of practice on dealing with infectious diseases on aircraft.
AB  - Increasing numbers of people are travelling to and from more distant destinations
      with the possibility of exposure to common as well as exotic disease. At the
      present time there are no readily accessible rules or guidance for dealing with
      possible cases of infectious disease occurring during international flights. A
      'Code of Practice on dealing with infectious disease on aircraft' is proposed as
      a ready means of dealing with the problem without excessive action or expense.

PMID- 7643346
TI  - Weaning: the general practitioner's perspective.

PMID- 7643347
TI  - The challenge of promoting physical activity.

PMID- 7643348
TI  - Public health in the United States.

PMID- 7643349
TI  - Effect of smoking on chronic inflammatory bowel disease.

PMID- 7643350
TI  - Direct marketing of cystic fibrosis carrier screening: commercial push or
      population need?

PMID- 7643351
TI  - Leukaemia and Sellafield: is there a heritable link?
AB  - The demonstration of a statistical association between paternal preconceptional
      irradiation and childhood leukaemia appeared to provide a satisfactory
      explanation for the excess of cases in the village of Seascale, close to the
      Sellafield nuclear installation, and became the basis of two legal claims for
      compensation. In the ensuing scientific debate the biological plausibility of a
      causal interpretation of this association focused on the heritability of
      leukaemia and a comparison of the genetic risks implied by this finding with
      current information on the induction of genetic damage by irradiation. After a
      wide ranging review of the mechanistic issues it is concluded that there is no
      genetic basis for a causal relationship and this, together with recent appraisals
      of epidemiological studies, suggests that the association between childhood
      leukaemia and paternal preconceptional irradiation exposure is most likely to be
      a chance finding.

PMID- 7643352
TI  - A new X linked recessive deafness syndrome with blindness, dystonia, fractures,
      and mental deficiency is linked to Xq22.
AB  - X linked recessive deafness accounts for only 1.7% of all childhood deafness.
      Only a few of the at least 28 different X linked syndromes associated with
      hearing impairment have been characterised at the molecular level. In 1960, a
      large Norwegian family was reported with early onset progressive sensorineural
      deafness, which was indexed in McKusick as DFN-1, McKusick 304700. No associated
      symptoms were described at that time. This family has been restudied clinically.
      Extensive neurological, neurophysiological, neuroradiological, and biochemical,
      as well as molecular techniques, have been applied to characterise the X linked
      recessive syndrome. The family history and extensive characterisation of 16
      affected males in five generations confirmed the X linked recessive inheritance
      and the postlingual progressive nature of the sensorineural deafness. Some
      obligate carrier females showed signs of minor neuropathy and mild hearing
      impairment. Restudy of the original DFN-1 family showed that the deafness is part
      of a progressive X linked recessive syndrome, which includes visual disability
      leading to cortical blindness, dystonia, fractures, and mental deficiency.
      Linkage analysis indicated that the gene was linked to locus DXS101 in Xq22 with
      a lod score of 5.37 (zero recombination). Based on lod-1 support interval of the
      multipoint analysis, the gene is located in a region spanning from 5 cM proximal
      to 3 cM distal to this locus. As the proteolipid protein gene (PLP) is within
      this region and mutations have been shown to be associated with non-classical PMD
      (Pelizaeus-Merzbacher disease), such as complex X linked hereditary spastic
      paraplegia, PLP may represent a candidate gene for this disorder. This family
      represents a new syndrome (Mohr-Tranebjaerg syndrome, MTS) and provides
      significant new information about a new X linked recessive sydromic type of
      deafness which was previously thought to be isolated deafness.

PMID- 7643353
TI  - Alagille syndrome: family studies.
AB  - Alagille syndrome (AGS) is one of the major forms of chronic liver disease in
      childhood with severe morbidity and a mortality of 10 to 20%. It is characterised
      by cholestasis of variable severity with paucity of interlobular bile ducts and
      anomalies of the cardiovascular system, skeleton, eyes, and face. Previous
      studies suggest a wide variation in the expression of the disease and a high
      incidence of new mutations. To determine more accurately the rate of new
      mutations and to develop criteria for detecting the disorder in parents we
      systematically investigated parents in 14 families with an affected child.
      Clinical examination was supplemented by liver function tests, echocardiography,
      radiographic examination of the spine and forearm, ophthalmological assessment,
      and chromosome analysis. Six parents had typical anomalies in two or more systems
      pointing to the presence of autosomal dominant inheritance. Systematic screening
      of parents for the features defined in this study should improve the accuracy of
      genetic counselling.

PMID- 7643354
TI  - Association study with two markers of a human homeogene in infantile autism.
AB  - Epidemiological data and family studies in autism show that there is a genetic
      susceptibility factor in the aetiology of this syndrome. We carried out an
      association study in infantile autism. Two markers of the homeogene EN2 involved
      in cerebellar development were tested in a population of 100 autistic children
      and in a population of 100 control children. With the MP4 probe showing a PvuII
      polymorphism, significant differences in the allele frequencies between the two
      populations were found (chi 2 = 7.99, df = 1, p < 0.01). With the MP5 probe
      showing an SstI polymorphism, no difference appeared (chi 2 = 1.17, not
      significant). Several clinical examinations allowed us to characterise the
      autistic children. Most of them had high scores for autistic behaviour and
      language disorders but low scores for neurological syndromes. Two children had a
      significant family history and six children had confirmed syndromes or diseases
      of genetic origin. Discriminant analysis between clinical and molecular data did
      not give significant results. These preliminary results must be supported by
      further analyses of this gene and by studies of its potential involvement in the
      pathophysiology of the autistic syndrome.

PMID- 7643355
TI  - Detecting deletions in the critical region for lissencephaly on 17p13.3 using
      fluorescent in situ hybridisation and a PCR assay identifying a dinucleotide
      repeat polymorphism.
AB  - During a study of lissencephaly in England and Wales, 23 children were identified
      with this diagnosis. They were classified as follows: three children had Miller
      Dieker syndrome (MDS), 13 had isolated lissencephaly sequence (ILS), two had type
      II lissencephaly, and five children were reclassified as focal or diffuse
      cortical dysplasia. Microdeletions of chromosome 17p13.3, also known as the
      Miller-Dieker critical region, have been associated with both MDS and ILS. We
      used the commercially available Oncor probe for fluorescent in situ hybridisation
      (FISH) studies on 14 patients and a further four were studied elsewhere.
      Deletions were identified in all three MDS patients and two of the ILS patients.
      These results are consistent with previously reported data. No deletions were
      found in those patients with focal or diffuse cortical dysplasia. In addition, a
      CA repeat polymorphism which maps to the Miller-Dieker critical region was
      studied in 12 families and was informative in nine; the results were consistent
      with the FISH data. We conclude that FISH is a reliable method to detect
      deletions in patients with MDS and ILS and also useful to identify chromosome
      rearrangements in their parents which are not detected by conventional
      cytogenetic analysis. The PCR assay, if informative, is also reliable and a
      useful alternative if only DNA is available. None of the five children with
      atypical radiological features had a deletion. We therefore suggest that as well
      as looking for other aetiologies a careful review of the diagnosis should be made
      of the MDS or ILS cases in whom a deletion is not found.

PMID- 7643356
TI  - A new transthyretin variant (Ser 24) associated with familial amyloid
      polyneuropathy.
AB  - An American kindred with systemic amyloidosis presenting with carpal tunnel
      syndrome, peripheral neuropathy, and cardiomyopathy is reported. The
      transthyretin gene of a patient was analysed by direct DNA sequencing and both
      cytosine and thymine were present at the first base of codon 24. This new point
      mutation in exon 2 results in the amino acid substitution of serine for proline
      in the A-B loop of the transthyretin molecule. DNA testing for this mutant allele
      by restriction fragment length polymorphism analysis based on the polymerase
      chain reaction is described.

PMID- 7643357
TI  - Stepwise or couple antenatal carrier screening for cystic fibrosis?: women's
      preferences and willingness to pay.
AB  - Several antenatal cystic fibrosis carrier screening trials have offered women
      testing by either the stepwise or the couple method. In this study, both
      approaches were described to women attending an antenatal clinic, who were then
      asked which method they preferred. An estimate of the value to women of each type
      of test was also ascertained using a "willingness to pay" (WTP) method. Of 450
      women, 279 (62%) preferred stepwise screening, 117 (26%) preferred couple
      screening, and 54 (12%) had no preference. Mean WTP for stepwise screening was 19
      pounds (95% CI 17.50 pounds-20.50 pounds), and that for couple screening was 18
      pounds (95% CI 16.50 pounds-19.50 pounds). The majority of women preferred
      stepwise screening although the average WTP for each method was similar.

PMID- 7643358
TI  - Perinatal lethal osteogenesis imperfecta.
AB  - Perinatal lethal osteogenesis imperfecta is the result of heterozygous mutations
      of the COL1A1 and COL1A2 genes that encode the alpha 1(I) and alpha 2(I) chains
      of type I collagen, respectively. Point mutations resulting in the substitution
      of Gly residues in Gly-X-Y amino acid triplets of the triple helical domain of
      the alpha 1(I) or alpha 2(I) chains are the most frequent mutations. They
      interrupt the repetitive Gly-X-Y structure that is mandatory for the formation of
      a stable triple helix. Most babies have their own private de novo mutation.
      However, the recurrence rate is about 7% owing to germline mosaicism in one
      parent. The mutations act in a dominant negative manner as the mutant pro alpha
      chains are incorporated into type I procollagen molecules that also contain
      normal pro alpha chains. The abnormal molecules are poorly secreted, more
      susceptible to degradation, and impair the formation of the extracellular matrix.
      The collagen fibres are abnormally organised and mineralisation is impaired. The
      severity of the clinical phenotype appears to be related to the type of mutation,
      its location in the alpha chain, the surrounding amino acid sequences, and the
      level of expression of the mutant allele.

PMID- 7643359
TI  - Superoxide dismutase mutations in an unselected cohort of Scottish amyotrophic
      lateral sclerosis patients.
AB  - Mutations in the Cu/Zn superoxide dismutase (SOD1) gene are responsible for some
      cases of familial amyotrophic lateral sclerosis (ALS). We have shown that SOD1
      mutations can also occur in apparently sporadic ALS. To establish how often this
      happens we have undertaken a study of the prevalence of SOD1 mutations in an
      unselected cohort of Scottish ALS patients, with both sporadic (n = 57) and
      familial (n = 10) disease. Single strand conformation polymorphism analysis was
      used to scan for new mutations, and selective restriction enzyme digestion to
      screen for 11 of the 20 SOD1 mutations published to date. We detected mutations
      in five (50%) of the familial ALS patients and also in four (7%) of the sporadic
      patients. One mutation, ile113thr, seems to be particularly prevalent in the
      Scottish population since it was detected in a total of 6/67 (9%) unrelated
      cases.

PMID- 7643360
TI  - De novo 1;10 balanced translocation in an infant with thanatophoric dysplasia: a
      clue to the locus of the candidate gene.
AB  - A female infant with thanatophoric dysplasia was found to have a de novo
      translocation involving chromosomes 1 and 10. The chromosome abnormality may
      represent an important clue in identifying the locus for the candidate gene
      responsible for this lethal skeletal dysplasia.

PMID- 7643361
TI  - Inversions in the factor VIII gene: improvement of carrier detection and prenatal
      diagnosis in Dutch haemophilia A families.
AB  - Haemophilia A is an X linked bleeding disorder caused by a heterogeneous spectrum
      of mutations in the factor VIII gene. It has recently been reported that about
      50% of severe haemophilia A cases are the result of an iversion in the factor
      VIII gene. The inversion results from homologous recombination between the A gene
      located in intron 22 of the FVIII gene and one of the two distal A genes, thus
      disrupting the coding sequence of the factor VIII gene. The inversion can be
      detected by conventional Southern blotting and hybridisation techniques. Here we
      present an analysis of 177 unrelated Dutch haemophilia A cases for the presence
      of an inversion. In 57% of the patients with severe disease an inversion was
      found and also in at least one of the 26 patients with moderately severe disease.
      The majority of inversions (85%) involved the most distal A gene, while in a
      minority (15%) the more proximal A gene was involved. We show that direct
      mutation detection greatly improves the assessment of carrier status and prenatal
      diagnosis for haemophilia A, especially in families with an isolated patient. The
      inversion is predominantly of grandpaternal origin.

PMID- 7643362
TI  - Severe intrauterine growth retardation with increased mitomycin C sensitivity: a
      further chromosome breakage syndrome.
AB  - We report an infant with pre- and postnatal microcephaly and growth retardation,
      a distinctive face, and developmental delay. The initial diagnosis was of Seckel
      syndrome. He became pancytopenic at 16 months and died soon after. His bone
      marrow was of normal cellularity but had a small lymphocyte infiltration.
      Increased spontaneous chromosome breakage was seen in blood and fibroblasts.
      Mitomycin C induced chromosome damage was increased and comparable to that seen
      in Fanconi anaemia. Reports of similar patients are reviewed. This entity of
      severe intrauterine growth retardation and increased mitomycin C sensitivity is
      hypothesised to be a distinct chromosome breakage syndrome.

PMID- 7643363
TI  - Partial trisomy 22 (q11.2-q13.1) as a result of duplication and pericentric
      inversion.
AB  - A case of a 27 year old male with a duplication of part of the long arm of
      chromosome 22 (22q11.2-q13.1) together with a pericentric inversion of the same
      chromosome is reported. Particular phenotypic features of note include absence of
      speech, persistent self-injury, lack of daily living skills, colobomata, and very
      poor vision. Similarities between this case and other case reports of
      duplications of the long arm of chromosome 22 are discussed.

PMID- 7643364
TI  - Congenital knee dislocation in a 49,XXXXY boy.
AB  - We report on a 12 year old mentally retarded boy who presented at birth with
      bilateral knee dislocations, dislocation of the right hip, and general joint
      laxity. Cytogenetic studies showed a 49,XXXXY karyotype. Hyperlaxity of joints is
      known to occur in 49,XXXXY patients, but congenital knee dislocation has not been
      reported. Rarely in 49,XXXXY and 49,XXXXX syndromes Larsen-like features may be
      seen. Patients with congenital joint dislocation or laxity, combined with other
      malformations, especially if psychomotor development is delayed, should be
      karyotyped to exclude chromosomal abnormalities.

PMID- 7643365
TI  - Exclusion of RET and Pax 3 loci in Waardenburg-Hirschsprung disease.
AB  - The RET and the Pax 3 genes have recently been shown to account for autosomal
      dominant Hirschsprung's disease (HSCR) and Waardenburg syndrome type 1 (WS1)
      respectively, which led us to consider them as candidate genes in the WS/HSCR
      association. Linkage analyses performed in a consanguineous WS/HSCR family
      support the view that neither the RET locus nor the Pax 3 locus are involved in
      the disease phenotype. Hence, at least one further locus altering neural crest
      cell development is responsible for the pleiotropic features observed in the
      WS/HSCR association.

PMID- 7643366
TI  - MURCS in a male?
AB  - A man with Klippel-Feil deformity, unilateral renal agenesis, and azoospermia is
      presented as a possible case of MURCS.

PMID- 7643367
TI  - Encephalocraniocutaneous lipomatosis with a mutation in the NF1 gene.
AB  - Encephalocraniocutaneous lipomatosis (ECCL) is a congenital hamartomatous
      disorder characterised by unilateral skin lesions, lipomas, and ipsilateral
      ophthamological and cerebral malformations. The disorder is thought to represent
      a localised form of Proteus syndrome. In this report, a child is described with
      ECCL and a de novo nonsense mutation in exon 29 (S1745X) of the neurofibromatosis
      type 1 (NF1) gene. Although it is possible that both ECCL and NF1 occur
      coincidentally in this patient, we favour the hypothesis that in exceptional
      cases a mutation in the NF1 gene might give rise to severe congenital
      malformations such as ECCL. Possible pathogenetic mechanisms for these
      malformations are discussed.

PMID- 7643368
TI  - International workshop on molecular genetics of haemochromatosis, held at Villa
      Feltrinelli, Gargnano (Bs), Italy, 25 September 1994.

PMID- 7643369
TI  - Huntington's disease in Saudi Arabia.

PMID- 7643370
TI  - Different muscle specific promoter characteristics in two sibs with Duchenne
      muscular dystrophy.

PMID- 7643371
TI  - Autosomal dominant simple microphthalmos: incomplete penetrance and variable
      expression in a large family.

PMID- 7643372
TI  - Grebe syndrome: a very severely affected case.

PMID- 7643373
TI  - Hemorrhagic gastritis due to syphilis. An unusual condition simulating lymphoma.

PMID- 7643374
TI  - Laparoscopic nephrectomy. A case report.

PMID- 7643375
TI  - Timing of prophylactic antibiotics in selected surgical procedures.

PMID- 7643376
TI  - It was a very good year.

PMID- 7643377
TI  - Breaking the silence.

PMID- 7643378
TI  - Utilization review law of the state of Mississippi.

PMID- 7643379
TI  - A single amino acid substitution in zinc finger 2 of Adr1p changes its binding
      specificity at two positions in UAS1.
AB  - The two zinc fingers of the yeast transcription factor Adr1p recognize the 6 bp
      sequence TTG GAG site in which the first finger, a His-X3-His finger, recognizes
      the G-rich triplet (GAG) and the second zinc finger, a His-X4-His finger,
      recognizes the T-rich sequence (TTG). Mutations were introduced into the alpha
      helical region of the second finger and the resultant mutant proteins were
      analyzed for DNA binding affinity and specificity in vitro and in vivo.
      Substituting His for Leu in the third position (+3) of the helix created a new
      binding specificity at two positions in the binding site. The mutant with His
      replacing Leu146(L146H) bound with high affinity to GGG GGG and with low affinity
      to TTG GGG. The single substitution at position +3 in the helix had the same
      effect on DNA binding specificity as substitution of the whole helix of the
      second finger with the helix of finger one. Changing Asp145 to Ala in the
      presence of His146 changed the apparent binding site of finger 2 to GT/CG. The
      L146H mutant zinc finger protein had the same binding specificity in vivo as in
      vitro. Changing the spacing between the His residues that ligand zinc in the
      second finger from four to three, the spacing found in the first finger of Adr1p
      and Zif268, did not alter the specificity or affinity of the wild-type or mutant
      protein.

PMID- 7643380
TI  - The structure of deoxy- and oxy-leghaemoglobin from lupin.
AB  - The leghaemoglobins have oxygen affinities 11 to 24 times higher than that of
      sperm whale myoglobin, due mainly to higher rates of association. To find out
      why, we have determined the structures of deoxy- and oxy-leghaemoglobin II of the
      lupin at 1.7 A resolution. Results confirm the general features found in previous
      X-ray analyses of this protein. The unique feature that has now emerged is the
      rotational freedom of the proximal histidine. In deoxy-leghaemoglobin the
      imidazole oscillates between two alternative orientations, eclipsing either the
      lines N1-N3 or N2-N4 of the porphyrin; in oxy-leghaemoglobin it is fixed in a
      staggered orientation. The iron atom moves from a position 0.30 A from the plane
      of the pyrrole nitrogen atoms in deoxy- to a position in the plane in oxy
      leghaemoglobin while the Fe-<N> bond distance remains constant at 2.02 A. The Fe
      O-O angle is 152 degrees, as in human haemoglobin. The oxygen is hydrogen-bonded
      to the distal histidine at N epsilon 2-O1 and N epsilon 2-O2 distance of 2.95 A
      and 2.68 A, respectively. The porphyrin is ruffled equally in deoxy- and oxy
      leghaemoglobins, due to rotations of the pyrrols about the N-Fe-N bonds, causing
      the methine bridges to deviate by up to 0.32 A from the mean porphyrin plane. The
      only feature capable of accounting for the high on-rate of the reaction with
      oxygen are the mobilities of the proximal histidine and distal histidine residues
      in deoxy-leghaemoglobin. The eclipsed positions of the proximal histidine in
      deoxy-leghaemoglobin maximize steric hindrance with the porphyrin nitrogen atoms
      and minimize pi-->p electron donation, while its staggered position in oxy
      leghaemoglobin reverses both these effects. Together with the oscillation of the
      imidazole between the two orientations, these two factors may reduce the
      activation energy for the reaction of leghaemoglobin with oxygen. The distal
      histidine is in a fixed position in the haem pocket in the crystal, but must be
      swinging in and out of the pocket at a high rate in solution to allow the oxygen
      to enter.

PMID- 7643382
TI  - Influence of protein conformation on disulfide bond formation in the oxidative
      folding of ribonuclease T1.
AB  - In oxidative protein folding the interdependence between the acquisition of an
      ordered native-like conformation and disulfide bond formation was investigated by
      using the C2S/C10N variant of ribonuclease T1 as a model. This protein of 104
      residues has a single disulfide bond between Cys6 and Cys103. In the reduced form
      it is unfolded in the presence of urea, but native-like folded when > or = 1.5 M
      NaCl is present. The influence of a folded conformation on the individual
      thiol/disulfide exchange reactions between the protein and glutathione could thus
      be studied in oxidative folding by varying the urea and NaCl concentrations. When
      the reduced protein was folded native-like the initial formation of the mixed
      disulfide between the protein and glutathione was decelerated about fourfold. The
      attachment of a glutathionyl moiety in this step destabilizes the protein by
      about 5 kJ mol-1 and led to a local unfolding near the two Cys residues. The
      reacting thiol groups still remained in close proximity for the subsequent
      intramolecular thiol/disulfide exchange reaction, but an increase in the energy
      of the transition state (e.g. by a hydrophobic environment or by steric strain)
      could be avoided. As a consequence the formation of the protein disulfide in this
      reaction was 100-fold faster when the mixed-disulfide species was in this ordered
      conformation. These results illustrate the importance of a low stability and a
      high flexibility of folding intermediates.

PMID- 7643381
TI  - Functional linkage between the active site of alpha-lytic protease and distant
      regions of structure: scanning alanine mutagenesis of a surface loop affects
      activity and substrate specificity.
AB  - Previous structural and kinetic characterization of mutations within the active
      site of alpha-lytic protease have demonstrated that amino acid residues in direct
      contact with the substrate are major substrate specificity determinants. The
      experiments described here identify residues 216-226 of alpha-lytic protease as a
      region of structure peripheral to the active site that also plays an important
      role in establishing the substrate specificity of the enzyme. Alanine
      substitution mutations within this surface loop of 19 amino acid residues
      significantly perturb the enzyme's specificity profile, despite being as far as
      21 A from the hydroxyl group of Ser195. The kinetic consequences of the mutations
      are remarkably independent of position within the loop and suggest that active
      site plasticity is affected more than static structure. Kinetic characterization
      of double mutants with the Met190-->Ala broad-specificity active site mutation
      reveals varying degrees of non-additivity and indicates that active site
      plasticity can be influenced through multiple sets of interactions. Although
      these results clearly demonstrate that tuning of serine protease activity is
      possible through remodelling of structure surrounding the active site, practical
      issues such as retaining compatibility with the folding mechanism and stability
      of the mature enzyme present significant obstacles to general application of the
      technique.

PMID- 7643384
TI  - Experimental analysis of the Schellman motif.
AB  - Statistical analysis of the protein database indicates that the presence of a
      particular sequence fingerprint, involving a Gly residue at position i, two
      hydrophobic residues at positions i + 1 and i-4, and a polar or Ala residue at
      position i-2, is found at the C-terminal end of alpha-helices 5.9 times more
      frequently than expected from a random distribution. This particular sequence
      fingerprint is frequently associated (approximately 50% of the cases) with a
      local motif known as the Schellman motif. Formation of this motif with the above
      fingerprint is accompanied by an interaction between the side-chains of the two
      hydrophobic residues (97% of the cases). To assess the role of this hydrophobic
      interaction in helix stability and in the formation of the Schellman motif, we
      have analysed by nuclear magnetic resonance (NMR) and far-UV circular dichroism
      (CD) a set of polyalanine-based peptides containing the sequence fingerprint
      described above. Our results show that this motif is not populated to a large
      extent in aqueous solution and contributes little to alpha-helix stability, the
      opposite to what has previously been found in two local motifs at the N termini
      of helices (hydrophobic staple and capping-box). Addition of 30% (v/v)
      trifluoroethanol results in the formation of the hydrophobic interaction between
      residues i-4 and i + 1 of the fingerprint, thus showing that there are no
      sequence or sterical reasons that prevent its formation in aqueous solution. This
      motif could be an example of a local interaction selected both on a stability
      basis and because of three-dimensional packing reasons.

PMID- 7643383
TI  - Nitrate and nitrite regulation of the Fnr-dependent aeg-46.5 promoter of
      Escherichia coli K-12 is mediated by competition between homologous response
      regulators (NarL and NarP) for a common DNA-binding site.
AB  - The NarL and NarP proteins are homologous response regulators that function to
      regulate anaerobic respiratory gene expression in response to nitrate and nitrite
      in Escherichia coli. Expression of the aeg-46.5 operon (anaerobically expressed
      gene at 46.5 minutes on the genetic map) is induced during anaerobic growth by
      the global transcriptional regulatory protein Fnr. aeg-46.5 operon expression is
      further induced by the NarP protein in response to nitrate or nitrite and this
      induction is antagonized by NarL. We used in vivo and in vitro techniques to
      investigate how these three transcriptional regulatory proteins control the
      activity of a single promoter. Deletion and mutational analysis of the aeg-46.5
      operon control region identified two distinct cis-acting elements. A sequence
      with similarity to the Fnr-binding site consensus, centered at position -64.5,
      was essential for Fnr-dependent anaerobic induction of aeg-46.5 operon
      expression. In all other naturally occurring Fnr-dependent promoters the primary
      Fnr-binding site is centered between -40 and -50. The second cis-acting element,
      a region of perfect symmetry centered at -44.5, shares sequence similarity with
      the NarL-binding site consensus. This region was required for nitrate and nitrite
      induction of aeg-46.5 operon expression. We purified the NarP and NarL proteins
      as maltose-binding protein (MBP) fusion proteins and investigated their
      interaction with the aeg-46.5 operon control region. Incubation with the phospho
      donor, acetyl phosphate, allowed both MBP-NarP and MBP-NarL to protect the -44.5
      region of the aeg-46.5 operon control region from DNase I cleavage. Single and
      double nucleotide substitutions in the -44.5 region reduced or abolished nitrate
      and nitrite induction of aeg-46.5 operon expression in vivo and prevented the
      binding of MBP-NarP and MBP-NarL to the control region in vitro. Presumably, the
      NarP and NarL proteins compete for the -44.5 binding site to regulate aeg-46.5
      operon expression in response to nitrate and nitrite. Apparently, only the NarP
      protein is competent to activate transcription of the aeg-46.5 operon when bound
      to the -44.5 region.

PMID- 7643385
TI  - Average core structures and variability measures for protein families:
      application to the immunoglobulins.
AB  - A variety of methods are currently available for creating multiple alignments,
      and these can be used to define and characterize families of related proteins,
      such as the globins or the immunoglobulins. We have developed a method for using
      a multiple alignment to identify an average structural "core", a subset of atoms
      with low structural variation. We show how the means and variances of core-atom
      positions summarize the commonalities and differences with a family, making them
      particularly useful in compiling libraries of protein folds. We show further how
      it is possible to describe the rotation and translation relating two core
      structures, as in two domains of a multi-domain protein, in a consistent fashion
      in terms of a "mean" transformation and a deviation about this mean. Once
      determined, our average core structures (with their implicit measure of
      structural variation) allow us to define a measure of structural similarity more
      informative than the usual root-mean-square (RMS) deviation in atomic position,
      i.e. a "better RMS." Our average structures also permit straightforward
      comparisons between variation in structure and sequence at each position in a
      family. We have applied our core-finding methodology in detail to the
      immunoglobulin family. We find that the structural variability we observe just
      within the VL and VH domains anticipates the variability that others have
      observed throughout the whole immunoglobulin superfamily; that a core definition
      based on sequence conservation, somewhat surprisingly, does not agree with one
      based on structural similarity; and that the cores of the VL and VH domains vary
      about 5 degrees in relative orientation across the known structures.

PMID- 7643386
TI  - Recurring local sequence motifs in proteins.
AB  - We describe a completely automated approach to identifying local sequence motifs
      that transcend protein family boundaries. Cluster analysis is used to identify
      recurring patterns of variation at single positions and in short segments of
      contiguous positions in multiple sequence alignments for a non-redundant set of
      protein families. Parallel experiments on simulated data sets constructed with
      the overall residue frequencies of proteins but not the inter-residue
      correlations show that naturally occurring protein sequences are significantly
      more clustered than the corresponding random sequences for window lengths ranging
      from one to 13 contiguous positions. The patterns of variation at single
      positions are not in general surprising: chemically similar amino acids tend to
      be grouped together. More interesting patterns emerge as the window length
      increases. The patterns of variation for longer window lengths are in part
      recognizable patterns of hydrophobic and hydrophilic residues, and in part less
      obvious combinations. A particularly interesting class of patterns features
      highly conserved glycine residues. The patterns provide a means to abstract the
      information contained in multiple sequence alignments and may be useful for
      comparison of distantly related sequences or sequence families and for protein
      structure prediction.

PMID- 7643387
TI  - Analysis of E. coli rho factor: mutations affecting secondary-site interactions.
AB  - To define and differentiate primary and secondary RNA binding sites within the
      linear sequence of the rho protein, we investigated two mutant alleles, rho-115
      and rhosuA1. They were first identified as defective in transcription termination
      in vivo, and later demonstrated to be defective in their interactions with RNA at
      the primary and secondary sites, respectively. Sequencing of rhosuA1 revealed a
      single lysine to glutamic acid residue change at position 352 (KE352), while rho
      115 carries two mutations, glycine99 to valine (GV99) and a proline235 to
      histidine (PH235). Proteins carrying single mutations at each of these three
      positions were purified and their characteristics compared to the wild-type
      protein. We found both KE352 and GV99 to be defective in secondary-site RNA
      activation, with Km values for r(C)10 of 100 microM and approximately 650 microM,
      respectively, compared to the wild-type value of 4 microM. These observed
      secondary-site defects correlated with decreased helicase and ATPase activities,
      as well as a loss of transcription termination activity in vitro. By contrast,
      PH235 was very efficient at interacting with r(C)10 at the secondary site, with a
      measured Km of 0.5 microM, and displayed the characteristics of a hyperactive
      rho, as judged by its ATPase, helicase and termination capabilities. Our results
      show that mutations at three very different locations in the polypeptide can
      affect secondary-site activation by RNA, and that these interactions play a
      pivotal role in ATP hydrolysis, helicase activity and transcription termination.

PMID- 7643388
TI  - The HEM proteins: a novel family of tissue-specific transmembrane proteins
      expressed from invertebrates through mammals with an essential function in
      oogenesis.
AB  - We report the identification of a new family of proteins, termed the HEM family,
      which show distinct expression patterns in blood cells and the central nervous
      system. Through the isolation and characterization of the corresponding brain
      specific Drosophila (dhem-2) and rat orthologues (Hem-2), and through the
      detection of the Caenorhabditis elegans Hem-2 orthologue in the database, we show
      that this family is conserved throughout evolution. HEM proteins show a conserved
      length ranging from 1118 to 1126 amino acid residues. Moreover, they are at least
      35% identical with each other and harbour several conserved membrane-spanning
      domains, indicative for their location on the cell surface. One of the members,
      the Drosophila orthologue dhem-2, was analysed in detail for its spatial
      expression pattern during development and for its mutant phenotype. dhem-2 is
      expressed maternally in the oocyte and shows uniform expression during the first
      half of embryogenesis, but becomes restricted to the brain and the nervous system
      during late embryogenesis, consistent with the expression of its vertebrate
      orthologue in the brain. One P-element insertion, located 39 base-pairs
      downstream from the dhem-2 transcription start site, causes female sterility, due
      to the fact that developmental processes in the oocyte are disturbed. Of the
      vertebrate HEM family members, the mammalian Hem-1 gene is expressed only in
      cells of hematopoietic origin, while Hem-2 is preferentially expressed in brain,
      heart, liver and testis.

PMID- 7643389
TI  - High-speed rotation and speed stability of the sodium-driven flagellar motor in
      Vibrio alginolyticus.
AB  - The Na(+)-driven flagellar motor in Vibrio alginolyticus rotates very fast.
      Rotation of a single flagellum on a stuck cell was measured by laser darkfield
      microscopy with submillisecond temporal resolution. The rotation rate increased
      with increasing external concentration of NaCl, and reached 1000 r.p.s. at 300 mM
      NaCl. The Na+ influx through the motor should determine the rotation period (tau)
      and affect the speed stability. Fluctuation of the rotation period was analyzed
      at various rotation rates (from approximately 50 r.p.s. to approximately 1000
      r.p.s.), which were changed by changing the external concentration of NaCl and
      the addition of a protonophore or a specific inhibitor. At high rotation rates
      (over 400 r.p.s.), the observed rotation was stable, and the standard deviation
      of tau (sigma tau) ranged from 7% to 16% of the average rotation period (< tau
      >). At low rotation rates (under 100 r.p.s), the rotation period tended to
      fluctuate, and the distributions of tau were non-Gaussian. The value of sigma tau
      ranged from 10 to 30% of < tau >. However, the observed minimum value of sigma
      tau at various rotation rates was approximately equal to the calculated standard
      deviation due to the rotational diffusion of the flagellar filament. These
      results suggest that the torque was stably generated at various Na+ influxes
      through the motor. We observed large fluctuations that cannot be explained by
      rotational diffusion. We discuss the factors that induce the large fluctuation.

PMID- 7643390
TI  - The capsid size-determining protein Sid forms an external scaffold on phage P4
      procapsids.
AB  - Although the phages P2 and P4 build their capsids from the same precursor, the
      product of the P2 N gene, the two capsids differ in size: P2 builds a 60 nm, T =
      7 capsid from 420 subunits, whereas P4 makes a 45 nm, T = 4 capsid from 240
      subunits. This difference leads to substantial changes in shell geometry and
      subunit interactions. Previous results have demonstrated that the P4 sid gene is
      responsible for the assembly of P4-sized shells. We have used cryo-electron
      microscopy and image reconstruction to determine the structure of a putative
      assembly intermediate of P4 capsids, produced in vivo from cloned genes. We
      demonstrate that Sid forms a P4-specific scaffold with icosahedral symmetry on
      the outside of the procapsid-like particles. The Sid molecules (60 or 120 copies)
      form lofty arches that interact with the gpN hexamers on the icosahedral 2-fold
      axes, and connect as trimers over the 3-fold axes, forming a continuous
      dodecahedrally shaped outer cage. The gpN shell inside the Sid cage is
      approximately 40 nm wide, consistent with the previously suggested maturational
      expansion. The main difference with respect to the mature P4 capsids is found in
      the hexamers, which appear strongly elongated and more protruding than in the
      mature shell. These and previous results are discussed in the light of a model
      for regulation of capsid size.

PMID- 7643391
TI  - Solution structure of the Oxytricha telomeric repeat d[G4(T4G4)3] G-tetraplex.
AB  - The solution structure of Oxytricha telomere sequence d[G4(T4G4)3] in 0.1 M Na+
      containing solution has been determined using a combined NMR-molecular dynamics
      approach including relaxation matrix refinement. This four G4 repeat sequence
      folds intramolecularly into a right-handed G-tetraplex containing four stacked G
      tetrads which are connected by two lateral T4 loops and a central diagonal T4
      loop. The guanine glycosidic bonds adopt a syn-anti alternation along the full
      length of the d[G4(T4G4)3] sequence while the orientation around adjacent G
      tetrads switches between syn.syn.anti.anti and anti.anti.syn.syn alignments. Four
      distinct grooves are formed by the parallel (two of medium width) and anti
      parallel (one wide and one narrow width) alignment of adjacent G-G-G-G segments
      in the G-tetraplex. The T4 residues in the diagonal loop are well-defined while
      the T4 residues in both lateral loops are under-defined and sample multiple
      conformations. The solution structure of the Na(+)-stabilized Oxytricha
      d[G4(T4G4)3] G-tetraplex and an earlier solution structure reported from our
      laboratory on the Na(+)-stabilized human d[AG3(T2AG3)3] G-tetraplex exhibit a
      common folding topology defined by the same syn/anti distribution of guanine
      residues along individual strands and around individual G-tetrads, as well as a
      common central diagonal loop which defines the strand directionalities. The well
      resolved proton NMR spectra associated with the d[G4(T4G4)3] G-tetraplex opens
      the opportunity for studies ranging from cation-dependent characterization of G
      tetraplex conformation and hydration to ligand and protein recognition of the
      distinct grooves associated with this folding topology.

PMID- 7643392
TI  - CH/pi interaction in the packing of the adenine ring in protein structures.
AB  - One of the weak but directional interactions in protein structures involves the O
      H or N-H bond that is oriented along the center of a benzene ring. Even a CH
      group can have enthalpically favorable interaction with an aromatic ring if the
      latter is made electron-rich by incorporating nitrogen atoms. This CH/pi
      interaction is brought into play in the binding of the adenine rings, which are
      sandwiched between protein residues such that saturated carbon atoms are on top
      of ring nitrogen atoms at distances of approximately 3.7 A. There is a
      preponderance of residues with branched side-chains that have specific locations
      on the tertiary fold that is employed for binding the adenine-containing
      cofactors. In addition to the conventional hydrogen bonding, the CH/pi
      interaction can be important for the recognition of DNA and RNA molecules by
      proteins. The main- and the side-chain atoms of the same residue can participate
      in both types of interaction, so that a protein can engage an adenine moiety by
      employing only a limited number of residues.

PMID- 7643393
TI  - Solution X-ray scattering analysis of cold- heat-, and urea-denatured states in a
      protein, Streptomyces subtilisin inhibitor.
AB  - Streptomyces subtilisin inhibitor (SSI), a homo-dimeric protein with a subunit of
      113 residues with two disulfide bonds, is known to exist at low pH in at least
      three distinct thermodynamic states namely, the native (N), cold-denatured (D')
      and heat-denatured (D). Small-angle X-ray scattering was used to analyze and to
      compare overall chain conformations of SSI in typical, N, D', D and urea
      denatured states (Durea). Molecular masses were determined from scattering
      intensities extrapolated to a scattering angle of zero, which showed that SSI
      exists as a homo-dimer in the N state, but as dissociated monomers in the D', D
      and Durea states. From Guinier plots of the scattering intensities, radii of
      gyration (Rg) were determined to be 20.1(+/- 1.8) A for N, and 20.7(+/- 1.3),
      25.8(+/- 1.5) and 32 to 35 A for D', D and Durea, respectively. Kratky plots for
      both N and D' exhibited a bell-shape indicating that the polypeptide chain has a
      globular part not only in N but also in D', while Kratky plots for D and Durea
      showed that the polypeptide chain has no globular part either in Durea or D.
      Combined with the results from circular dichroism and 1H NMR spectra, a picture
      emerges for the polypeptide chain conformation of SSI such that in N it is a
      globular dimer close to that in the crystal, in Durea it is totally disordered
      and expanded nearly to a fully random chain with restrictions only from the
      disulfide bridges, in D the entire chain is disordered and expanded but with
      considerable local intra-chain interactions, and in D' the chain consists of a
      part with a unique tertiary structure and a part disordered and expanded to a
      degree comparable to D.

PMID- 7643395
TI  - Stabilization of fluid cholesteric phases of collagen to ordered gelated
      matrices.
AB  - Liquid crystalline assemblies occur spontaneously in highly concentrated
      solutions of type I acid-soluble calf skin collagen. The degree of order,
      identified by optical microscopy in polarized light, varies from a random
      distribution of molecules at low concentrations to highly organized structures as
      the concentration increases up to 80 mg/ml. Ultrastructural studies using
      classical techniques of chemical fixation are inappropriate for liquid
      crystalline phases due to the absence of stable links maintaining their three
      dimensional order. In order to analyse the collagen liquid crystalline phases by
      electron microscopy the viscous preparations were stabilized under ammonia
      vapour. Observations of the gels in polarized light indicated that the liquid
      crystalline order, established at acidic pH in a sol state, persists at neutral
      pH in a gel state. Transmission electron microscopic observations allow us to
      validate the geometrical model interpreted from observations in polarizing
      microscopy, that is continuously twisting orientations in cholesteric phases
      characterized by typical series of arced patterns when viewed in oblique
      sections. A significant result is that the ultrastructure of the stabilized
      liquid crystalline collagen faithfully mimics fibrillar patterns described in
      vivo in extracellular matrices. This strongly supports the hypothesis that liquid
      crystalline properties are involved in the morphogenesis of collagen matrices.

PMID- 7643394
TI  - Steric-blocking by tropomyosin visualized in relaxed vertebrate muscle thin
      filaments.
AB  - Although widely accepted, the steric-blocking model of vertebrate skeletal muscle
      regulation has not been confirmed. Previous attempts to directly visualize
      tropomyosin in relaxed skeletal muscle and demonstrate that it interferes with
      the crossbridge-thin filament contractile cycle were unsuccessful. In the work
      reported here, tropomyosin was resolved in electron micrographs of native thin
      filaments isolated from relaxed vertebrate striated muscle. Three-dimensional
      helical reconstructions of these filaments showed continuous narrow strands of
      density, representing tropomyosin, which followed the outer domains of successive
      actin monomers. The results obtained from fitting the atomic model of filamentous
      actin to these reconstructions illustrate, and are consistent with, the mechanism
      of steric-blocking, since tropomyosin was found to be positioned on the actin
      surface of thin filaments over clusters of identifiable amino acids required for
      myosin crossbridge docking.

PMID- 7643396
TI  - Fixation of the quaternary structures of human adult haemoglobin by encapsulation
      in transparent porous silica gels.
AB  - We have used the sol-gel method to encapsulate oxy- and deoxy haemoglobins in
      transparent wet porous silica gels and fixed their original functional states
      with the retention of the reversible oxygenation properties as well as the intact
      spectroscopic properties. Haemoglobin originally encapsulated in aerobic gel
      binds oxygen non-cooperatively with very high affinity, corresponding to that for
      the last oxygen molecule binding to haemoglobin in solution. In contrast,
      haemoglobin originally encapsulated in anaerobic gel binds oxygen non
      cooperatively with very low affinity, comparable to that for the first oxygen
      molecule binding to haemoglobin in solution. Furthermore, a detailed comparison
      of visible absorption spectra of deoxygenated haemoglobins originally
      encapsulated in aerobic and anaerobic gels indicates the retention of their
      original quaternary structures during the oxygenation or deoxygenation process.
      These results demonstrate that oxygen affinities of oxy- and deoxyhaemoglobins in
      solution can be satisfactorily fixed by encapsulation in wet porous silica gels,
      which presumably prevents the changes in the quaternary structures of
      haemoglobin. In addition, these results suggest a new capability of the sol-gel
      method to control the structural states of a variety of proteins, and further
      open up a new area of investigation of protein structure-function relationships.

PMID- 7643397
TI  - Evidence that uncharged tRNA can inhibit a programmed translational frameshift in
      Escherichia coli.
AB  - In the modified release factor 2 (RF2) programmed translational frameshift (with
      a sense codon replacing the wild-type in-frame UGA codon at the shift site),
      ribosomes shift +1 into the reading frame for an out-of-frame reporter fused to
      the frameshift sequence. Partitioning of ribosomes between the out-of-frame shift
      and in-frame reading depends on the codon at the shift site and on the levels of
      tRNA decoding the in-frame codon. Overexpression of a tRNA species cognate to the
      in-frame codon at the shift site significantly reduces the frequency of frame
      shifting, presumably by facilitating in-frame reading, which would reduce
      production of the out-of-frame reporter. However, since overexpression of a tRNA
      increases levels of both charged and uncharged tRNA, it is possible that
      uncharged cognate tRNA might be able to reduce the frequency of the frameshift,
      by entering the A site on the ribosome. To test this, we manipulated charged and
      uncharged tRNA levels in vivo, using the tryptophan analog tryptophan
      hydroxamate, which increases the proportion of uncharged tRNA(Trp) by competing
      with cognate amino acid tryptophan for tryptophanyl-tRNA synthetase, thereby
      reducing protein synthesis. We report here that a slight but reproducible
      reduction in the relative frequency of the frameshift is observed when tryptophan
      hydroxamate is added to cells containing the modified RF2 shift with UGG (Trp
      codon) at the shift site. When tRNA(Trp) is overexpressed from another plasmid,
      the shift frequency drops three- to fourfold, as expected, however, this
      reduction is still seen in the presence of the analog. Thus, under conditions
      when most of the tRNA(Trp) is apparently uncharged, excess tRNA(Trp) still causes
      a significant reduction in the frameshift when UGG is at the shift site,
      providing evidence that uncharged cognate tRNA also can inhibit this frameshift.

PMID- 7643398
TI  - Production of a chimeric fibroin light-chain polypeptide in a fibroin secretion
      deficient naked pupa mutant of the silkworm Bombyx mori.
AB  - The allelic Nd-s and Nd-sD mutations of the silkworm Bombyx mori are mapped to
      the same locus as that of the fibroin light (L)-chain gene (Fib-L). The silkworm
      carrying the homozygous Nd-s or Nd-sD mutation secretes less than 0.3% of the
      normal level of fibroin and produces a thin cocoon (naked pupa). In this study,
      cDNA sequences of the Nd-s and Nd-sD L-chains were compared with the cDNA and
      genomic sequences of the L-chain of the B. mori J-139 strain, a normal-level
      producer of fibroin. The two mutant cDNA sequences are almost identical except
      for one base change in the coding region. The N-terminal half of the L-chain
      encoded by exons I to III is identical between the mutants and J-139, but the
      rest of the molecule is completely different. The C-terminal half of the Nd-sD
      mutant L-chain is encoded by two exons, IV' and V', which are brought into
      proximity with the exon III by recombination between sequences in the third
      intron and in the far downstream region with concomitant loss of a region
      containing exons IV to VII. Sequences corresponding to exons IV' and V' are
      present about 10 kb downstream of the L-chain gene in the J-139 genome. Their
      homologous sequences have not been found in the DNA and protein databases. The
      chimeric L-chain molecule of about 27 kDa is present in posterior silk glands of
      Nd-s and Nd-sD strains without disulfide-bonding to the fibroin heavy (H-) chain,
      as revealed by Western blotting with the antibody specific to the C-terminal half
      of the mutant L-chain.

PMID- 7643399
TI  - Novel mutagenic properties of abasic sites in Saccharomyces cerevisiae.
AB  - Abasic sites are particularly important in mutation research because they are
      frequently the ultimate lesion in chemical mutagenesis, and because they are
      believed to be a paradigm for non-pairing lesions. Although preferential
      insertion of dAMP ("A-rule") opposite the lesion has been observed in almost all
      previous studies with other organisms, we find that in budding yeast,
      Saccharomyces cerevisiae, the preferred nucleotide is dCMP, suggesting that yeast
      has a "C-rule", at least with respect to the vector constructs used. These
      constructs contained a single abasic site specifically located within a 28
      nucleotide single-stranded region in an otherwise duplex vector. Nucleotide
      insertions were determined by sequence analysis of replicated vectors taken from
      a random set of yeast transformants. In three different sequence contexts, the
      frequencies of dCMP and dAMP insertion were 83% and 13%, 62% and 31%, and 85% and
      8%, respectively. A similar bias in favor of cytosine insertion was found using
      vectors that were entirely single-stranded. However, a preference for dAMP
      insertion was found when Escherichia coli, rather than yeast, was transfected
      with samples of the same gapped duplex vector DNA. Preferential insertion of dCMP
      is not likely to have arisen by previously proposed mechanisms, but is also
      unlikely to have occurred by a primer/template misalignment mechanism, in which a
      nearby template guanine directs the insertion of cytosine. Predominant dCMP
      insertion was observed even when template guanine bases were excluded from a
      region extending 19 nucleotides 5', and 13 nucleotides 3', to the abasic site.

PMID- 7643400
TI  - Membrane topology of the MotA protein of Escherichia coli.
AB  - The MotA protein of Escherichia coli is a component of the flagella that
      functions together with the MotB protein in transmembrane proton conduction. It
      is an integral membrane protein, with four hydrophobic segments that might
      traverse the membrane and two short segments that are predicted to be in the
      periplasm. In a previous study of the accessibility of MotA to various proteases,
      evidence for periplasmic segments was not obtained, probably because they are
      small. Here, we report site-directed sulfhydryl labeling experiments which show
      that two segments of MotA are exposed on the periplasmic side of the membrane,
      while the rest of the protein is in the cytoplasm. These experiments establish
      that the main features of the suggested model for MotA topology are correct,
      furnishing a basis for more detailed structure-function studies of the MotA/MotB
      proton channel.

PMID- 7643402
TI  - Crystal structure of L-2-hydroxyisocaproate dehydrogenase from Lactobacillus
      confusus at 2.2 A resolution. An example of strong asymmetry between subunits.
AB  - L-2-Hydroxyisocaproate dehydrogenase (L-HicDH) from Lactobacillus confusus, a
      homotetramer with a molecular mass of 33 kDa per subunit, belongs to the protein
      family of the NAD(+)-dependent L-2-hydroxycarboxylate dehydrogenases. L-HicDH was
      crystallized with ammonium sulphate as precipitant in the presence of NAD+. The
      crystals belong to the trigonal space group P3(2)21, with a = 135.9 A and c =
      205.9 A, and diffract X-rays to 2.2 A resolution. The crystal structure was
      solved by Patterson search and molecular replacement techniques and refined to an
      R-value of 21.4% (2.2 to 8 A). The final structure model contains one NAD+
      molecule and one sulphate ion per subunit, with 309 water molecules. An unusual
      feature of this crystal structure is the deviation of the protein subunits from
      non-crystallographic symmetry, which is so strong that it can be detected
      globally by self-rotation calculations in reciprocal space. This asymmetry is
      especially pronounced in the environment of the active site; it is reflected also
      in the nicotinamide conformation of NAD+ and allows some conclusions to be drawn
      about the catalytic mechanism. In this context, an "inner active site loop" is
      identified as a structural element of fundamental functional importance.
      Furthermore, with knowledge of the crystal structure of L-HicDH the differences
      in substrate specificity between L-HicDH and the L-lactate dehydrogenases can be
      partly explained.

PMID- 7643401
TI  - X-ray scattering titration of the quaternary structure transition of aspartate
      transcarbamylase with a bisubstrate analogue: influence of nucleotide effectors.
AB  - The regulation of aspartate transcarbamylase (ATCase) involves various
      conformational changes, including a large quaternary structure rearrangement.
      This is directly related to a major change in its solution X-ray scattering curve
      upon binding the bisubstrate analogue N-(phosphonacetyl)-L-aspartate (PALA),
      allowing us to monitor directly the amount of the different quaternary structures
      present in solution. Data were analysed by singular vector decomposition without
      any prior assumption as to the number of quaternary structure states. Scattering
      curves in the presence of variable concentrations of PALA, alone or with
      saturating CTP or ATP, can be accounted for with only two states. Consequently
      the method gives the fraction of molecules in either state. Whereas CTP slightly
      decreases the proportion of molecules in the R state, ATP has no detectable
      effect, whatever the amount of PALA ligated to ATCase. The requirement for only
      two quaternary structures, suggesting a concerted transition, promoted us to test
      the ability of the classical model, proposed by Monod, Wyman and Changeux, to
      account for our data. By and large, it is satisfactory as regards the homotropic
      effect of PALA and the observed effect of CTP, although it remains incompatible
      with some other observations, which support the involvement of more indirect
      mechanisms in the inhibitory properties of CTP. But ATP does not directly
      influence the T to R transition and consequently must act by a totally different
      mechanism.

PMID- 7643403
TI  - Crystal structure of reduced bovine erythrocyte superoxide dismutase at 1.9 A
      resolution.
AB  - Cu,Zn superoxide dismutase was investigated crystallographically in the reduced
      form. Co-ordinate errors were estimated by comparing two independently refined
      models, based on two different data sets. This gave a detailed error estimation
      as opposed to the standard sigma A and Luzzati plots, which estimate only the
      overall error. The high quality of the final model, obtained after scaling
      together the two data sets, combined with the error estimates allowed a detailed
      analysis of the protein and solvent structures. An automatic procedure for
      building and refining solvent structure was tested and found to give reproducible
      results. Contrary to results obtained from spectroscopic studies, the co
      ordination of the metal ions in the catalytic site is preserved in the crystal
      structure of the reduced enzyme, as compared with the crystal structure of the
      oxidised form. Analysis of the solvent reveals a well-defined chain of closely
      packed, hydrogen-bonded water molecules filling the active site groove. This
      structural feature could serve as a hydrogen bond relay for efficient delivery of
      protons to the active centre. Analysis of electron density suggests that Glu119
      is covalently modified. The modification, if originated in vivo, could have a
      role in the catalytic mechanism and could affect the overall electrostatic field
      in the active site. There are significant differences between the active sites of
      the two crystallographically independent monomers. They are explained in terms of
      local differences in the crystal environment.

PMID- 7643404
TI  - The three-dimensional solution structure of the NK-2 homeodomain from Drosophila.
AB  - We describe the NMR determination of the three-dimensional structure of a 77
      amino acid residue protein, which consists of the 60 residue NK-2 homeodomain
      from Drosophila melanogaster and adjacent amino acid residues. The NK-2
      homeodomain protein is part of a 723 amino acid residue protein which is
      expressed early in embryonic development in part of the central nervous system.
      NK-2 was characterized using both a natural abundance and a uniformly 15N
      enriched sample by two-dimensional and three-dimensional NMR experiments. The
      average root-mean-square deviation for 30 structures for residues 8 to 53 is 0.40
      A for the backbone heavy-atoms and 0.72 A for the backbone and side-chain heavy
      atoms. These structures were obtained from 986 NOE-derived upper and lower bound
      restraints. The three-dimensional structure contains three helices which consist
      of homeodomain amino acid residues 10 to 22, 28 to 38 and 42 to 52, as well as a
      turn between helix II and III, characteristic of homeodomains. Residues 53 to 60
      of the DNA recognition helix are not fully ordered in the absence of DNA. In the
      free state this segment adopts a flexible but helix-like structure between
      residues 53 and 56 and is disordered from residues 57 to 60 although, as shown
      previously, the helix elongates by eight residues upon binding to DNA. The role
      of variable residues 52, 54 and 56 in determining the structure and flexibility
      of the recognition helix, as well as the stability of the NK-2 homeodomain as
      manifested by its thermal denaturation, are discussed.

PMID- 7643405
TI  - Global fold determination from a small number of distance restraints.
AB  - We have designed a distance geometry-based method for obtaining the tertiary fold
      of a protein from a limited number of structure-specific distance restraints and
      the secondary structure assignment. Interresidue distances were predicted from
      patterns of conserved hydrophobic amino acids deduced from multiple alignments. A
      simple model chain representing the protein was then folded by projecting its
      distance matrix into Euclidean spaces with gradually decreasing dimensionality
      until a final three-dimensional embedding was achieved. Tangled conformations
      produced by the projection steps were eliminated using a novel filtering
      algorithm. Information on various aspects of protein structure such as
      accessibility and chirality was incorporated into the conformation refinement,
      increasing the robustness of the algorithm. The method successfully identified
      the correct folds of three small proteins from a small number of restraints,
      indicating that it could serve as a useful computational tool in protein
      structure determination from NMR data.

PMID- 7643406
TI  - Self-incorporation of coenzymes by ribozymes.
AB  - RNA molecules that are assembled from the four standard nucleotides contain a
      limited number of chemical functional groups, a characteristic that is generally
      thought to restrict the potential for catalysis by ribozymes. Although
      polypeptides carry a wider range of functional groups, many contemporary protein
      based enzymes employ coenzymes to augment their capabilities. The coenzymes
      possess additional chemical moieties that can participate directly in catalysis
      and thereby enhance catalytic function. In this work, we demonstrate a mechanism
      by which ribozymes can supplement their limited repertoire of functional groups
      through RNA-catalyzed incorporation of various coenzymes and coenzyme analogues.
      The group I ribozyme of Tetrahymena thermophila normally mediates a phosphoester
      transfer reaction that results in the covalent attachment of guanosine to the
      ribozyme. Here, a shortened version of the ribozyme is shown to catalyze the self
      incorporation of coenzymes and coenzyme analogues, such as NAD+ and
      dephosphorylated CoA-SH. Similar ribozyme activities may have played an important
      role in the "RNA world," when RNA enzymes are thought to have maintained a
      complex metabolism in the absence of proteins and would have benefited from the
      inclusion of additional functional groups.

PMID- 7643407
TI  - Distribution of genetic diversity in relation to chromosomal inversions in the
      malaria mosquito Anopheles gambiae.
AB  - The epidemiology of malaria in Africa is complicated by the fact that its
      principal vector, the mosquito Anopheles gambiae, constitutes a complex of six
      sibling species. Each species is characterized by a unique array of paracentric
      inversions, as deduced by karyotypic analysis. In addition, most of the species
      carry a number of polymorphic inversions. In order to develop an understanding of
      the evolutionary histories of different parts of the genome, we compared the
      genetic variation of areas inside and outside inversions in two distinct
      inversion karyotypes of A. gambiae. Thirty-five cDNA clones were mapped on the
      five arms of the A. gambiae chromosomes with divisional probes. Sixteen of these
      clones, localized both inside and outside inversions of chromosome 2, were used
      as probes in order to determine the nucleotide diversity of different parts of
      the genome in the two inversion karyotypes. We observed that the sequence
      diversity inside the inversion is more than three-fold lower than in areas
      outside the inversion and that the degree of divergence increases gradually at
      loci at increasing distance from the inversion. To interpret the data we present
      a selectionist and a stochastic model, both of which point to a relatively recent
      origin of the studied inversion and may suggest differences between the
      evolutionary history of inversions in Anopheles and Drosophila species.

PMID- 7643408
TI  - Identification and chromosomal distribution of DNA sequence segments conserved
      since divergence of Escherichia coli and Bacillus subtilis.
AB  - DNA sequence segments conserved since divergence of Escherichia coli and Bacillus
      subtilis were identified, using the GenBank sequence database. Chromosomal
      locations of the conserved segments were compared between the two bacteria, and
      the following three features were observed. (1) Although the two genomes are
      nearly identical in size, chromosomal arrangements of the conserved segments are
      considerably different from each other. (2) In many cases, chromosomal locations
      of a conserved segment in the two species have deviated from each other by a
      multiple of 60 degrees. (3) There are many instances in which a contiguous
      segment in one genome is split into two or more segments located at distinct
      positions in the other genome, and these split segments were found to tend to lie
      on the E. coli or B. subtilis genome separated by distances of multiples of 60
      degrees. On the basis of these observations, genome organizations of the two
      bacteria were discussed in terms of genome doublings as well as random
      chromosomal rearrangements.

PMID- 7643409
TI  - Paralogous origin of the rhodopsinlike opsin genes in lizards.
AB  - Rhodopsinlike opsins constitute a distinct phylogenetic group (Yokoyama 1994,
      Mol. Biol. Evol. 11:32-39). This RH2 group includes the green-sensitive opsins in
      chicken and goldfish and the blue-sensitive opsin in a nocturnal lizard gecko. In
      the present study, we isolated and sequenced the genomic DNA clones for the RH2
      opsin gene, rh2Ac, of the diurnal lizard Anolis carolinensis. This single-copy
      gene spans 18.3 kb from start to stop codons, making it the longest opsin gene
      known in vertebrates. Phylogenetic analysis strongly suggests that rh2Ac is more
      closely related to the chicken green opsin gene than to the gecko blue opsin
      gene. This gene tree differs from the organismal tree, where the two lizard
      species should be most closely related, implying that rh2Ac and the gecko blue
      sensitive opsin genes have been derived from duplicate ancestral genes.

PMID- 7643410
TI  - Evolution of protamine P1 genes in mammals.
AB  - Protamine P1 genes have been sequenced following PCR amplification from 11
      mammals representing five major mammalian orders: Rodentia (rat and guinea pig),
      Carnivora (cat and bear), Proboscidea (elephant), Perissodactyla (horse), and
      Artiodactyla (camel, deer, elk, moose, and gazelle). The predicted amino acid
      sequence for these genes together with previously reported sequences results in a
      data set of 25 different P1 genes and 30 different P1 amino acid sequences. The
      alignment of all these sequences reveals that protamines are amongst the most
      rapidly diverging proteins studied. In spite of the large number of differences
      there are conserved motifs that are also common to birds such as the N-terminal
      ARYR followed by the triple alternating SRSRSR phosphorylation site. The central
      region contains 3 arginine clusters consisting of 5-6 arginines each. The C
      terminus appears to be the most variable region of the protamines. Overall the
      molecular evolution of P1 genes is in agreement with the expected species
      evolution supporting that these genes have evolved vertically.

PMID- 7643411
TI  - A tandemly repeated DNA family originated from SINE-related elements in the
      European plethodontid salamanders (Amphibia, Urodela).
AB  - We have characterized a highly repetitive family, named Hy/Pol III, in the genome
      of the European salamanders Hydromantes (Plethodontidae). This family consists of
      short, tandemly repeated sequences organized in clusters, scattered through the
      genome as shown both by in situ hybridization to chromosomes and by Southern blot
      hybridization. The repeat unit is about 200 bp in length and it is a composite
      element since it contains a SINE-like retroposon with a tRNA structure, flanked
      by two short direct repeats. The whole element itself is bordered by two other
      direct repeats. The sequence data suggest that two elements, presumably derived
      from polymerase III transcripts, have been inserted one into the other, giving
      rise to the observed composite structure. During evolution the Hy/Pol III family
      was then amplified by tandem duplication at the DNA level. The inferred
      relationships between Hy/Pol III members from three representative species of the
      European Hydromantes suggests that a subfamily structure characterizes the
      evolutionary history of this family.

PMID- 7643412
TI  - Dictyostelium discoideum mitochondrial DNA encodes a NADH:ubiquinone
      oxidoreductase subunit which is nuclear encoded in other eukaryotes.
AB  - Complex I, a key component of the mitochondrial electron transport system, is
      thought to have evolved from at least two separate enzyme systems prior to the
      evolution of mitochondria from a bacterial endosymbiont, but the genes for one of
      the enzyme systems are thought to have subsequently been transferred to the
      nuclear DNA. We demonstrated that the cellular slime mold Dictyostelium
      discoideum retains the ancestral characteristic of having mitochondria encoding
      at least one gene (80-kDa subunit) that is nuclear encoded in other eukaryotes.
      This is consistent with the cellular slime molds of the family Dictyosteliaceae
      having diverged from other eukaryotes at an early stage prior to the loss of the
      mitochondrial gene in the lineage giving rise to plants and animals. The D.
      discoideum mitochondrially encoded 80-kDa subunit of complex I exhibits a twofold
      higher mutation rate compared with the homologous chromosomal gene in other
      eukaryotes, making it the most divergent eukaryotic form of this protein.

PMID- 7643413
TI  - Improved dating of the human/chimpanzee separation in the mitochondrial DNA tree:
      heterogeneity among amino acid sites.
AB  - The internal branch lengths estimated by distance methods such as neighbor
      joining are shown to be biased to be short when the evolutionary rate differs
      among sites. The variable-invariable model for site heterogeneity fits the amino
      acid sequence data encoded by the mitochondrial DNA from Hominoidea remarkably
      well. By assuming the orangutan separation to be 13 or 16 Myr old, a maximum
      likelihood analysis estimates a young date of 3.6 +/- 0.6 or 4.4 +/- 0.7 Myr (+/-
      1 SE) for the human/chimpanzee separation, and these estimates turn out to be
      robust against differences in the assumed model for amino acid substitutions.
      Although some uncertainties still exist in our estimates, this analysis suggests
      that humans separated from chimpanzees some 4-5 Myr ago.

PMID- 7643414
TI  - The contribution of DNA slippage to eukaryotic nuclear 18S rRNA evolution.
AB  - Six of 204 eukaryotic nuclear small-subunit ribosomal RNA sequences analyzed show
      a highly significant degree of clustering of short sequence motifs that indicates
      the fixation of products of replication slippage within them in their recent
      evolutionary history. A further 72 sequences show weaker indications of sequence
      repetition. Repetitive sequences in SSU rRNAs are preferentially located in
      variable regions and in particular in V4 and V7. The conserved region immediately
      5' to V7 (C7) is also consistently repetitive. Whereas variable regions vary in
      length and appear to have evolved by the fixation of slippage products, C7 shows
      no indication of length variation. Repetition within C7 is therefore either not a
      consequence of slippage or reflects very ancient slippage events. The
      phylogenetic distribution of sequence simplicity in small-subunit rRNAs is
      patchy, being largely confined to the Mammalia, Apicomplexa, Tetrahymenidae, and
      Trypanosomatidae. The regions of the molecule associated with sequence simplicity
      vary with taxonomic grouping as do the sequence motifs undergoing slippage.
      Comparison of rates of insertion and substitution in a lineage within the genus
      Plasmodium confirms that both rates are higher in variable regions than in
      conserved regions. The insertion rate in variable regions is substantially lower
      than the substitution rate, suggesting that selection acts more strongly on
      slippage products than on point mutations in these regions. Patterns of
      coevolution between variable regions may reflect the consequences of selection
      acting on the incorporation of slippage-derived sequences across the gene.

PMID- 7643415
TI  - Evolution of nuclear rDNA ITS sequences in the Cladophora albida/sericea clade
      (Chlorophyta).
AB  - Ribosomal DNA ITS sequences were compared among 13 different species and
      biogeographic isolates from the monophyletic "albida/sericea clade" in the green
      algal genus Cladophora. Six distinct ITS sequence types were found, characterized
      by multiple insertions and deletions and high levels of nucleotide substitution.
      Conserved domains within the ITS regions indicate the presence of ITS secondary
      structure. Low transition/transversion ratios among the six types and nearly
      symmetrical tree-length frequency distributions indicate some saturation, and low
      phylogenetic signal. Although branching order among five of the six ITS sequence
      types could not be resolved, estimates of ITS sequence divergence as compared
      with 18S divergence in a subset of the taxa suggests that the origin of the
      different ITS types is probably in the mid-Miocene (12 Ma ago) but that
      biogeographic isolates within a single ITS type (including both Pacific and
      Atlantic representatives) have probably dispersed on a time scale of thousands
      rather than millions of years.

PMID- 7643416
TI  - ADH evolution and the phylogenetic footprint.
AB  - The evolution of any given protein reflects the interplay between proximal
      selective forces involving the conservation of protein structure and function and
      more general populational factors that shape the action and efficiency of natural
      selection. In an attempt to address that interplay, we have analyzed patterns of
      amino acid replacement within a well-conserved molecule, alcohol dehydrogenase
      (ADH), in the Drosophilidae. A sliding window, moved along the protein sequence
      in order to quantify the extent of change at each amino acid position, reveals
      heterogeneous amounts of replacement across the molecule when all ADH sequences
      are analyzed simultaneously. Surprisingly, the replacement profile for ADH
      differs significantly in the melanogaster, mulleri, and Hawaiian subgroups,
      reflecting the imprint of the differing evolutionary histories of each of these
      assemblages on the evolution of this conservative molecule.

PMID- 7643417
TI  - Sequence analysis and structural features of the largest known protamine isolated
      from the sperm of the archaeogastropod Monodonta turbinata.
AB  - Protamine of the archaeogastropod mollusc Monodonta turbinata has been isolated
      and characterized. With a mass of 13,476 Da, it is the largest known protamine.
      Amino acid sequence of this protamine (106 residues) was established from data
      provided by automated sequence analysis and mass spectrometry of the protein and
      of its fragments. The primary structure of the NH2-terminal region exhibits
      repetitive sequence motifs "Basic-Ser" (mainly R-S) and both central and COOH
      terminal regions are composed by arginine clusters. The amino acid sequence of
      Monodonta turbinata protamine shows structural similarities with other protamines
      from invertebrates and from birds and mammals.

PMID- 7643418
TI  - Partial sequence of ribulose-1,5-bisphosphate carboxylase/oxygenase and the
      phylogeny of Prochloron and Prochlorococcus (Prochlorales).
AB  - The prochlorophytes, oxygenic photosynthetic prokaryotes having no
      phycobiliprotein but possessing chlorophylls a and b, have been proposed to have
      a common ancestry with green chloroplasts, yet this is still controversal. We
      report here that partial sequence comparisons of the large subunit of ribulose
      1,5'-bisphosphate carboxylase/oxygenase, including sequence data from two
      prochlorophytes, Prochlorococcus and Prochloron, indicate that Prochlorococcus is
      more closely related to a photosynthetic bacterium, Chromatium vinosum (gamma
      purple bacteria), than to cyanobacteria, while Prochloron is closely related to
      the prochlorophyte Prochlorothrix and to cyanobacteria. The molecular
      phylogenetic tree indicates that a common ancestor of Prochlorococcus and gamma
      purple bacteria branched off from the land plant lineage earlier than Prochloron,
      Prochlorothrix, and cyanobacteria.

PMID- 7643420
TI  - Does very short patch (VSP) repair efficiency vary in relation to gene expression
      levels?

PMID- 7643419
TI  - Structural and thermodynamic properties of DNA uncover different evolutionary
      histories.
AB  - We propose an index of DNA homogeneity (IDH) based on a binary distribution model
      that quantifies structural and thermodynamic aggregates present in DNA primary
      structures. Extensive analysis of sequence databases with the IDH uncovers
      significant constraints on DNA sequence other than those derived from codon usage
      or protein function. This index clearly distinguishes between organisms of
      different evolutive origins and places them in disjoint domains of DNA sequence
      space.

PMID- 7643421
TI  - The impact of extramarital relationships on the continuation of marriages.
AB  - Two groups of practicing therapists were asked to describe in depth a specific
      extramarital affair with which they were very familiar--whether as therapist,
      relative, or friend or were themselves involved. Of 62 cases, 21, or 34%, ended
      in divorce--in the therapists' judgments as a consequence of the infidelity. In
      27 cases, or 43.5%, the marriages were preserved, but in an overall dysphoric or
      negative atmosphere. In 4 cases, or 6%, the marriages were intact but either the
      marriage was "blah" or empty in quality or the future of the marriage was judged
      as still in doubt. Only in 9 cases, or 14.5%, were the marriages reported intact
      and characterized by improvement and growth. Of these, 4 were cases of one-time
      affairs. Analysis of the direct impact of the affair on the betrayed spouses
      showed that the majority of the betrayed husbands and wives suffered significant
      damage to their self-image, personal confidence, or sexual confidence, feelings
      of abandonment, attacks on their sense of belonging, betrayals of trust, enraged
      feelings, and/or a surge of justification to leave their spouses. The judgments
      of the therapists reporting the cases were that fully 89% of the betrayed spouses
      either were consciously aware of the infidelity or, even if not acknowledging,
      really knew, and that even the majority of the betrayed spouses who claimed
      consciously that they opposed their spouses' behavior were unconsciously in
      collusion with them.

PMID- 7643422
TI  - The sexoanalytical treatment of ego-dystonic homosexuality.
AB  - After clarifying some definitions, the author attempts to identify homosexuality
      through the sexual individuation process and to trace its various ontogenetic
      inconsistencies. Two clinical case studies are provided to further illustrate the
      sexoanalytic treatment of ego-dystonic homosexuality.

PMID- 7643423
TI  - HIV-positive people, HIV-negative partners.
AB  - More relationships exist today between HIV-positive and HIV-negative partners.
      This article explores the underlying dynamics that might account for this
      phenomenon. Codependency theories may explain these relationships for some
      couples. For other couples, it is suggested that positive-negative homosexual
      relationships may be influenced by both unhealthy and healthy gay developmental
      experiences as well as by a sense of compassion. The article addresses both HIV
      positive people choosing HIV-negative partners and vice versa. Treatment issues
      for the various theories are discussed and recommendations are made.

PMID- 7643424
TI  - Sexual functioning and attitudes of eating-disordered women: a follow-up study.
AB  - The sexual experiences and attitudes of eating disorder patients are receiving
      increased professional attention. However, empirical work in this area has
      generally focused on these patients at the point of initial evaluation. In the
      current study we report the results of a follow-up questionnaire completed by
      women who had been treated in our clinic (N = 42) for either anorexia nervosa
      (restricting type) or bulimia nervosa (purging type). We found that former
      anorectic patients were less likely to return the questionnaire and, of those who
      did, there was a trend toward anorectic women's being less likely to be in a
      romantic/erotic relationship. Almost all of the women had engaged in sexual
      intercourse, and former anorectic patients did not differ from bulimics with
      regard to age at first coitus. Anorectics were less likely than bulimics to have
      engaged in masturbation and also scored lower on a measure of sexual esteem.
      Although there were no differences between the two groups with regard to current
      level of sexual functioning, erotophobia/erotophilia, or sexual satisfaction, the
      women in our sample exhibited less sexual interest and more negative affect
      during sex than did a normative sample. Also, nearly 40% of our sample indicated
      clinically significant levels of sexual discord with their current partner.
      Results are discussed with regard to prior research, interventions, and further
      study.

PMID- 7643425
TI  - The scaling of premarital sexual permissiveness revisited: test results of
      Reiss's new short form version.
AB  - A new four-item version of the widely used Reiss Premarital Sexual Permissiveness
      (PSP) Scale is described and analyzed. The purpose of our research was to see if
      this much quicker to answer format will equal the high scaling attributes of the
      earlier and longer versions. Samples of students from the United States (N = 217)
      and Sweden (N = 186) were administered the short form. The analysis and data are
      presented and compared with the results of the original, longer versions of the
      scale. Results indicated that the four-item version met all Guttman scale
      requirements. Comparisons among scales indicated that criteria measurement scores
      were higher for the four-item version than they were for Reiss's earlier
      versions. The ways in which the new scale may be used are discussed, including
      the possible use of only one or two items from this new format as a quick and
      accurate attitudinal assessment of premarital sexual permissiveness.

PMID- 7643426
TI  - Prescribed masturbation in sex therapy: a critique.
AB  - The goal of this paper is to show from an interactional or systemic perspective
      how intimacy may be damaged through traditional sex therapy approaches. This is
      in opposition to stated claims by sex therapists, who have, since the pioneering
      work of Masters and Johnson, sought to improve intimacy by removing the
      impediment of poor sexual response. Prescribed masturbation in sex therapy is
      identified as particularly problematic in its potential for iatrogenic effects.
      These potentials are demonstrated from a relational perspective and from a
      functional perspective. Prescribed masturbation, intended to narrow the focus of
      attention from the "distraction" of a partner's response, may actually serve to
      further damage the openness and trust necessary for truly rewarding sexual
      expression. Difficulties in a relationship that preclude the trust necessary for
      open sexual interaction ought to be addressed before any sexual activity is
      prescribed. If clinicians' work circumvents the interactional component of the
      dysfunction, they may be guilty of colluding with clients in protecting them from
      intimacy. Recommended alternatives for clinicians are offered.

PMID- 7643427
TI  - A risk assessment for lead in birds.
AB  - Ecotoxicologists and ecologists have examined the effects of pollutants on
      individuals and populations largely in terms of one or only a few effects. Yet
      the recent trend toward a holistic approach to ecological risk assessment
      suggests that a rigorous paradigm should be applied to toxicants, from hazard
      identification to risk characterization. Recent discussions have recognized that
      an up-front problem formulation phase is more critical in ecological risk
      assessment than it is for human health risk assessment. In this article a
      modified environmental health risk assessment paradigm is used to examine the
      risk of lead to birds. This risk analysis is largely conceptual, based on
      laboratory and field data, and incorporates information currently available. The
      model expands the hazard identification phase to create a target identification
      phase that includes the identification of receptors, endpoints, relationships,
      spatial and temporal scales, and indicators. The target identification phase is
      unique to the particular hazard, species, population, or community being
      examined. Lead can cause mortality, or can indirectly affect populations through
      effects on the food base, avian behavior, reproductive success, and recruitment.
      Lead can (1) decrease the abundance and availability of prey, (2) bioaccumulate
      in prey causing increased lead toxicosis in predators, or (3) increase prey
      availability by interfering with its hiding or escape behavior. Moreover, lower
      abundance of prey can lead to starvation or nutrient deficiencies, which amplify
      the absorption and retention of lead. Lead also causes decreases in clutch and
      egg size, mortality of embryos and nestlings, depression of growth, and deficits
      in behavior that affect survival. Lead decreases migratory behavior, and
      increases vulnerability to cold stress, hunters, and other predators. Research
      needs for evaluating the risk of lead in birds include obtaining data on (1)
      metal dynamics within various tissues as a function of dose and time since
      initial exposure, (2) low-level effects on embryos, (3) effects on chicks
      following fledging and in the period prior to recruitment, (4) effects on adult
      foraging skills and reproductive behavior, and (5) the relationship between
      effects from exposure in the laboratory and those from exposure in the wild. This
      latter point is extremely important, particularly if wild birds have other means
      of ridding the body of lead not available or less apparent to laboratory birds.

PMID- 7643428
TI  - Immunomodulatory activities of extracellular metallothionein. II. Effects on
      macrophage functions.
AB  - Metallothionein (MT) is a thiol-rich protein that is rapidly induced by exposure
      to heavy metal cations. We have previously demonstrated that exogenous MT
      stimulates murine splenocytes to proliferate, but inhibits humoral responses to
      antigen. These observations suggest that metallothionein released from cells has
      a complex role in heavy metal-mediated immune dysfunction. Here we examine one
      possible mechanism by which MT mediates suppression of humoral immunity. Exposure
      of macrophages to 20 microM MT did not affect their ability to engulf opsonized
      sheep erythrocytes, but in the presence of 20 microM MT, peritoneal macrophages
      were stimulated to produce increased levels of oxygen radicals. These results
      correlated with observations that while macrophage phagocytosis of opsonized
      Candida albicans was unaltered by the presence of exogenous MT, killing of the
      engulfed yeast cells was dramatically enhanced by 20 microM MT. Amounts of free
      cadmium and zinc equimolar to that added as Zn,Cd-MT had no effect on
      candidacidal activity. MT was also found to significantly decrease lymphocyte
      proliferation mediated by macrophage activity. Biotinylated MT (MT-b) bound
      specifically to the plasma membranes of these macrophages, suggesting that
      membrane-associated molecules of the macrophage may transduce a signal mediated
      by MT binding. These results demonstrate that macrophages are a sensitive target
      for MT-mediated immunomodulation and that some of the consequences of the MT
      interaction with macrophages may be alterations in the capacity to produce an
      effective immune response and increased extracellular exposure to damaging free
      radicals.

PMID- 7643430
TI  - Nasal inflammatory responses in children exposed to a polluted urban atmosphere.
AB  - Southwest Metropolitan Mexico City (SWMMC) preadolescent children have been
      exposed to a highly polluted urban atmosphere most of their lives. The main
      objective of this study was to determine by nasal lavage (NAL) the acute
      inflammatory nasal influx elicited in these children upon exposure to three
      different polluted days. Ozone, the main criteria pollutant for SWMMC, varied
      both in the number of hours above the National Ambient Air Quality Standard
      (NAAQS), which is 0.12 ppm as a 1-h maximum concentration not to be exceeded more
      than once per year, and in the maximal concentrations in the preceding three NAL
      sampling dates. Nasal neutrophilic influx, the surface expression of the B2
      integrin CD11b on the nasal polymorphonuclear leukocytes (PMNs), rhinoscopic
      findings, respiratory symptoms, and nasal cytologies were evaluated in the 38
      exposed children and in the 28 control children living in a nonpolluted Pacific
      coast port. SWMMC children had an average daily outdoor exposure of 7.7 h and
      complained of nasal mucus secretion, epistaxis, intermittent nasal obstruction,
      diurnal cough episodes, and chest discomfort. Nasal mucosal atrophy by rhinoscopy
      was present in 37/38, and all children had an abnormal nasal cytology. Exposed
      children had significantly higher nasal PMNs and nasal PMN-CD11b expression than
      controls. PMN median values in exposed children were higher than controls on all
      sampling dates (November 12, p < .001; November 17, p < .001; and November 24, p
      < .00001). Interestingly, a lower nasal neutrophilic response (p < .0004) was
      recorded in the SWMMC children 18 h after exposure to the highest O3
      concentrations (up to 0.307 ppm) and the largest number of hours with O3 > 0.12
      ppm (7 h). The question of a competing inflammatory response at the
      bronchioalveolar level with structural damage is raised. These NAL findings
      underscore the need to restrict outdoor activity in SWMMC children during the
      months of greater potential exposure to ozone.

PMID- 7643429
TI  - Maternal and fetal toxicity of methylmercuric chloride administered to pregnant
      Fischer 344 rats.
AB  - Various doses of methylmercuric chloride (MMC) were administered orally to
      pregnant Fischer 344 rats on d 7 of gestation. On d 20 of gestation the dams were
      laparotomized under ether anesthesia, and the fetuses were removed. Maternal body
      weights were decreased for 2 d and 6 d in rats given 10 and 20 mg/kg MMC, and
      were continuously decreased for those given 30 mg/kg MMC. Maternal weight gain of
      each group was decreased to 86.2%, 78.9%, and 61.9% of control group on d 20 of
      gestation. The reduction of litter weight was greatly enhanced with increasing
      MMC doses, presumably due to postimplantation loss, which was already increased
      at high treatment levels. The LD50 of MMC for fetuses was determined to be 16.5
      mg/kg. Mercury content in maternal organs was highest in kidney, followed by
      blood, spleen, liver, and brain, while in fetal organs it was highest in liver.
      Fetal liver and brain contained more mercury than maternal liver and brain.
      However, fetal kidney retained less mercury than maternal kidney. Fetal
      ossification center was not completely formed in sternebrae, particularly in
      fifth and second bones, pelvic bones, and pectoral phalanges of fetuses in rats
      treated with 30 mg/kg MMC. The ossified lengths of skeletal bone stained with
      alizarin red S were developed least in fifth sternebrae, metacarpals in the
      pectoral girdle, and ischium in the pelvic girdle, and were severely retarded in
      development as position of the ribs goes from the sixth bone (center) to the
      first and 13th bone (each edge). These results indicate that MMC is embryotoxic
      in Fischer 344 rats.

PMID- 7643431
TI  - Effects of simultaneous administration of ethanol on styrene metabolism under fed
      and fasted conditions in the perfused rat liver.
AB  - The purpose of this study was to clarify the simultaneous administration of
      ethanol on styrene metabolism in the perfused rat liver under fed and fasted
      conditions. Styrene uptake rate, production rate of styrene glycol, oxygen
      consumption rate, and changes in reduced pyridine nucleotide fluorescence were
      monitored in the perfused rat liver. The effects of ethanol on parameters of
      styrene metabolism were observed in rat livers under fed and fasted conditions:
      fed (group I), fasted (group II), and fasted with xylitol in the perfusate (group
      III). The simultaneous administration of ethanol and styrene significantly
      decreased styrene uptake rate, production rate of styrene glycol, and oxygen
      consumption rate, and produced significant reduction of pyridine nucleotide
      fluorescence as compared with the single administration of styrene in groups I
      and III. In contrast, the simultaneous administration of ethanol and styrene
      significantly increased the production of styrene glycol and oxygen consumption
      as compared with the single administration of styrene in group II. Significant
      effects on the styrene uptake rate and the reduced pyridine nucleotide
      fluorescence were observed with regard to factors of both nutritional status and
      the interaction between ethanol and nutritional status by two-way analysis of
      variance. These findings showed that the effects of ethanol on styrene metabolism
      in the liver were dependent upon the nutritional status of the animal. The fed
      and fasted conditions affected the effect of ethanol on styrene metabolism by
      changing the supply of NADPH to the mixed-function oxidase system. In conclusion,
      ethanol suppressed styrene metabolism in the fed condition, but enhanced it in
      the fasted condition. This phenomenon should be considered in the prevention of
      occupational hazard of styrene exposure in industrial workers with alcohol
      drinking habits and nutritional problems.

PMID- 7643432
TI  - Effect of environmental tobacco smoke on the metabolism of (-)-trans
      benzo[a]pyrene-7,8-dihydrodiol in juvenile ferret lung and liver.
AB  - To evaluate the effects of "environmental tobacco smoke" (ETS) on developing
      lungs, juvenile ferrets were exposed to ETS at an average total particulate
      concentration of 381 +/- 97 mg/m3 for 2 h at the breathing zone. Twenty-four
      hours after the exposure, the ferrets were sacrificed and the metabolism of (-)
      trans-benzo[a]pyrene-7,8-dihydrodiol was studied in the lung and liver
      homogenates. The rate of conversion of (-)-trans-benzo[a]pyrene-7,8-dihydrodiol
      to the ultimate carcinogen (+)-anti-benzo[a]pyrene-7,8-dihydrodiol-9,10- epoxide
      was twofold higher in the liver than that observed in the lung of control
      ferrets. After ETS exposure, the formation of free benzo[a]pyrene-7,8-dihydrodiol
      9,10-epoxide was increased by 62% in the lung (p < .01). The DNA-bound
      metabolites were significantly increased only in the lung, while protein-bound
      metabolites were significantly increased in the liver after ETS exposure.
      Although glutathione conjugates tended to be increased both in the lung and
      liver, sulfate conjugates were significantly decreased in the lung after ETS
      exposure (p < .05). (+)-trans-Benzo[a]pyrene-7,8-dihydrodiol was used to study
      the relative contributions of cytochrome P-450 and peroxyl radical-mediated
      formation of benzo[a]-pyrene-7,8-dihydrodiol-9,10-epoxide. Peroxyl radical- and P
      450-mediated conversion of (+)-trans-benzo[a]pyrene-7,8-dihydrodiol to
      benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide was proportionately equal in the
      ferret lung, whereas in the liver the P-450-mediated pathway was predominant.
      After ETS exposure there was a tendency for P-450-mediated formation of
      benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide to increase. These results
      demonstrate significant differences in the metabolism of (-)-trans-benzo[a]pyrene
      7,8-dihydrodiol by the lung and liver of juvenile ferrets and suggest a
      significant role of peroxyl radical-mediated formation of (+)-anti-benzo[a]pyrene
      7,8-dihydrodiol-9,10-epoxide in the lung, which may help explain discrepancy
      between the levels of P-450 and amounts of DNA adducts of polycyclic aromatic
      hydrocarbons in different organs in smokers.

PMID- 7643433
TI  - Ketone potentiation of haloalkane-induced hepato- and nephrotoxicity. I. Dose
      response relationships.
AB  - Carbon tetrachloride (CCl4) induced hepatotoxicity and chloroform (CHCl3) induced
      nephrotoxicity were evaluated in male Sprague-Dawley rats pretreated with acetone
      (A), methyl ethyl ketone (MEK), and methyl isobutyl ketone (MiBK). Dose-response
      relationships for A, MEK, and MiBK potentiation of CCl4-induced hepatotoxicity
      and CHCl3-induced nephrotoxicity were compared. A, MEK, and MiBK pretreatment at
      a dosage of 6.8 mmol/kg, given daily for 3 d, markedly potentiated CCl4-induced
      liver toxicity as indicated by a decrease in the CCl4 ED50 to 3.4, 4.6, and 1.8
      mmol/kg, respectively, compared to vehicle-pretreated rats (17.1 mmol/kg).
      Similarly, pretreatment with these ketones (13.6 mmol/kg) potentiated CHCl3
      kidney toxicity but to a lesser degree; CHCl3 ED50 values for vehicle-, A-, MEK-,
      and MiBK-pretreated rats were 3.4, 1.6, 2.1, and 2.2 mmol/kg, respectively. Our
      results indicate a potency ranking profile for the potentiation of CCl4
      hepatotoxicity of MiBK > A > MEK and of A > MEK > or = MiBK for CHCl3
      nephrotoxicity. These dissimilar ranking profiles could be due to differences in
      mechanisms of action for the two target sites.

PMID- 7643434
TI  - Lack of significant promoting activity by benzene in the rat liver model of
      carcinogenesis.
AB  - The promoting activity of benzene on rat liver carcinogenesis was investigated.
      The chemical was tested for its ability to enhance the growth of preneoplastic
      foci, as detected by gamma-glutamyl transpeptidase (GGT) staining in
      diethylnitrosamine (DENA) initiated hepatocytes. Two weeks after receiving a
      single ip dose of 200 mg/kg DENA, F344 rats were given daily oral doses of 400
      mg/kg benzene (5 d/wk) for 6 wk. At wk 3 after the experiment began, all animals
      underwent partial hepatectomy, and at wk 8 were sacrificed. Following benzene
      treatment, no variation in the liver/body weight ratio was observed. After
      scoring of foci in liver slides, no significant difference in foci number and
      area could be observed between rats treated with DENA plus benzene and rats
      treated with DENA alone. Practically no foci were observed in the liver of rats
      treated only with benzene. The lack of benzene promoting activity in the liver
      model is discussed.

PMID- 7643436
TI  - The American Academy of Implant Dentistry: its changing role.

PMID- 7643435
TI  - Channel-specific induction of the cyclosporine A-sensitive mitochondrial
      permeability transition by menadione.
AB  - It is well established that menadione, 2-methyl-1,4-naphthoquinone, impairs the
      ability of rat liver mitochondria to accumulate and retain calcium. However, it
      remains unclear whether this reflects inhibition of mitochondrial calcium uptake
      or stimulation of calcium release by menadione. The purpose of the current
      investigation was to determine whether interference with mitochondrial calcium
      homeostasis by menadione reflects a selective activation of the cyclosporine A
      sensitive pore, independent of actions on other mitochondrial calcium channels.
      Mitochondrial calcium flux was monitored using the metallochromic dye arsenazo
      III. Treatment of mitochondria with menadione caused a concentration-dependent
      decrease in net calcium accumulation followed by a delayed release of the
      accumulated calcium and concurrent mitochondrial swelling. Both the maximum
      steady-state accumulation of calcium and the delay preceding calcium release
      decreased as a function of calcium concentration. The release of calcium did not
      occur via the Na+/Ca2+ antiport or reversal of the uptake uniport, as neither
      diltiazem nor ruthenium red prevented the menadione-stimulated calcium release.
      In contrast, cyclosporine A, a potent inhibitor of the permeability transition
      pore, completely inhibited menadione-induced calcium release and the associated
      swelling. Furthermore, the menadione-induced inhibition of calcium accumulation
      was completely prevented in the presence of cyclosporine A, indicating a
      selective stimulation of calcium release by menadione, rather than inhibition of
      calcium uptake. These data provide the first definitive description of a specific
      action of menadione to stimulate mitochondrial calcium release through a
      cyclosporine A-sensitive pathway, independent of altering the regulation of other
      recognized calcium channels associated with the inner mitochondrial membrane.

PMID- 7643437
TI  - The rationale for soft-tissue grafting and vestibuloplasty in association with
      endosseous implants: a literature review.
AB  - Significant soft-tissue complications have been reported around endosseous
      implant permucosal abutments. Peri-implantitis with associated bone loss can have
      a negative effect on the long-term prognosis of the implant reconstruction. The
      rationale for soft-tissue grafting and vestibuloplasty techniques is presented in
      the form of a literature review. The implant sulcular epithelium, permucosal
      seal, and the peri-implant connective tissues are discussed. The etiology of soft
      tissue complications as well as the significance of attached gingiva surrounding
      implant abutments are presented along with techniques for surgical intervention.

PMID- 7643438
TI  - Evaluation of a hydroxylapatite (HA)/resorbable suture implant for alveolar ridge
      augmentation.
AB  - A new type of hydroxylapatite (HA) particle configuration and implant system for
      alveolar ridge augmentation was investigated. The PermaRidge implant system was
      designed to provide better HA particle handling and retention characteristics.
      Torous-shaped particles were bound together with resorbable sutures into rope
      like bundles. The implants were placed as a single unit rather than as individual
      particles delivered via syringe. Six adult beagle dogs underwent bilateral
      mandibular tooth extraction. After an eight-week healing period, the animals had
      PermaRidge implants placed on the right side and HA particles alone placed on the
      left side. Two animals were killed at each of four, eight, and 16 weeks post
      operatively. Radiographically, the PermaRidge implants maintained initial
      augmentation height throughout the course of the study. There was no compaction
      of the implant or problems with containment and migration of the HA particles.
      The HA particles alone demonstrated an approximate 25% decrease in augmentation
      height with time in situ. The majority of augmentation height was lost within the
      first four weeks post-operatively. There was also significant particle compaction
      and migration present in the implant sites. Histologically, the PermaRidge
      implants demonstrated bone growth into the augmentation, often extending 2-3
      particle diameters (2-3 mm). The remainder of the implant was filled with dense
      connective tissue. There was intimate contact of the ingrown bone with the HA
      surface. The HA particles alone demonstrated minimal bone ingrowth, with
      extensive fibrous tissue infiltration. The results indicate that the PermaRidge
      implant system may provide a viable alternative to HA particles alone for the
      augmentation of the deficient alveolar ridge.

PMID- 7643439
TI  - An evaluation of electrodischarged prototype implants in rabbit tibia: a
      preliminary study.
AB  - This is the first in a series of biological investigations using a porous implant
      fabricated by a novel process known as electrodischarge compaction (EDC). This
      process uses Ti-6A1-4V powder and electrical energy to construct a beaded porous
      implant without any compromise in physical characteristics, often found with
      conventional sintering. The purpose of this study was to evaluate the bone
      response in rabbit tibia of a porous titanium prototype implant fabricated by
      this new technique. One hundred forty-four porous EDC-fabricated implants were
      placed into the tibia of 36 New Zealand rabbits. Animals were placed into one of
      six time periods (2, 4, 8, 12, 18, and 24 weeks). At the appropriate time period,
      animals were killed, and bone ingrowth was evaluated qualitatively by light and
      scanning electron microscopy. Bone/implant interface bond strength was also
      measured. Slight bone ingrowth was observed as early as the two-week time period
      and increased in depth at each time period for the duration of the study.
      Implant/bone bond strength was measurable at four weeks and continued until
      reaching a plateau at week 12. The results of this study suggest that this novel
      EDC implant may be suitable for continued development of an easily fabricated,
      cost-effective dental implant.

PMID- 7643440
TI  - Reactions of bone tissue in old rats to three different implant materials.
AB  - This study compares the bone responses of old rats when implanted with
      hydroxyapatite ceramic (HAC)-coated titanium, high-density HAC, and uncoated
      titanium. Twelve two-year-old Wistar rats were used in this study. Cylindrical
      implants were placed into each tibia, and the animals were killed seven, 14, 28,
      or 56 days after implantation. Undecalcified sections were prepared and were then
      stained with toluidine blue. The healing process was examined histologically, and
      histomorphometric measurements were made with a computer-based image analyzer to
      quantify the percentage of implant-bone contact. The results indicated that the
      HAC-coated implants were superior to the uncoated titanium implants in relation
      to bone contact. In the cases where the bone-free surface of HAC coating was
      dissolved, macrophages were often seen on the surface of the implant. Although
      further longitudinal data are needed to evaluate the decrease of HAC coating, in
      this animal model, HAC-coated implants may be useful for osseous response in
      bones of poor quality.

PMID- 7643441
TI  - Comparative three-dimensional analysis of two finite-element endosseous implant
      designs.
AB  - The finite-element method was used to assess force distribution to the cortical
      and cancellous bone surrounding two HA-coated, cylindrical implant designs, one
      grooved, the other smooth-sided. It was shown that, with both designs, large
      compressional stresses occurred in a small volume of bone at the coronal portion
      of the mandibular ridge. The stresses produced gave rise to a large stress
      gradient in the interface area. Significant differences were noted between the
      two designs in this area. It was also noted that the majority of the loading
      occurred in the cortical region of the mandibular ridge.

PMID- 7643442
TI  - A clinical technique revisited: treating the peri-implantoclasia of
      hydroxyapatite-coated subperiosteal implants.
AB  - A technique for treating peri-implantoclasia around HA-coated subperiosteal
      implants is described. Once infection has invaded the HA coating of a
      subperiosteal implant, it is difficult to eliminate the infection via local
      curettage or antibiotic treatment. The technique includes: (1) removing the
      contaminated HA coating from the implant, (2) removing all granulomatous tissue
      from the affected site, and (3) impelling granulation and secondary intention
      epithelial from the apex of the lesion up into the oral cavity using the
      technique of Jermyn. This technique minimizes the resulting pocket depth adjacent
      to the cervix.

PMID- 7643443
TI  - [Progress in the treatment of aplastic anemia].

PMID- 7643444
TI  - [Indication of allogeneic bone marrow transplantation (BMT) from HLA identical
      sibling in adult acute myeloblastic leukemia--comparative study of BMT and
      chemotherapy in patients with the first remission state. Nagoya BMT Group. Japan
      Adult Leukemia Study Group].
AB  - The indication of allogeneic bone marrow transplantation (BMT) from HLA identical
      siblings during the first remission of acute myeloblastic leukemia was discussed
      according to the results of BMT and chemotherapy study groups. The comparison of
      disease free survival between both groups was done, after selection biases such
      as risk factors and time of BMT were adjusted by multivariate analysis or matched
      pair analysis. In conclusion, patients with more than one high risk factors for
      leukemia relapse, that is, high peripheral white blood cell count (PBC) (>
      20,000/cmm) at diagnosis or more than two remission induction courses should be
      considered for BMT, and the indication of treatments for patients with no high
      risk factors should be determined depending on situations of the disease and
      patient's intention.

PMID- 7643445
TI  - [A preliminary analysis of unrelated marrow transplantations facilitated by the
      Japan Marrow Donor Program (JMDP)].
AB  - Between January 1993 and June 1994, the JMDP facilitated marrow donations from
      unrelated donors for 171 patients with malignant and non-malignant disorders. The
      median age of the patients was 21 years. All patients received marrow from
      phenotypically HLA -A, -B, -DR identical donors. About half of the patients wrer
      treated with total body irradiation (TBI)-containing regimens and about 80% of
      the patients received short-courses methotrexate and cyclosporine for graft
      versus-host disease (GVHD) prophylaxis. Eight out of 171 patients, (4.7%) had
      graft failure and 63 out of 144 patients (44%), who survived for more than 30
      days posttransplant, developed grade II to IV acute GVHD. The incidence of
      chronic GVHD was 47% (extensive form; 27%); most of them were
      progressive/quiscent type. The incidence of moderate to severe acute GVHD was
      higher than that observed in sibling transplants. On the other hand, the
      incidence of chronic GVHD was similar to that observed in sibling transplants.
      Overall survival at 1.5 years posttransplant was about 50% with no significant
      differences between diseases. The age correlated significantly with the survival
      in standard risk leukemia but not in high-risk leukemia. Despite the risk of
      graft failure and acute GVHD, this preliminary analysis demonstrates that
      transplantation of marrow from unrelated donors can be an effective treatment for
      certain hematologic disorders.

PMID- 7643446
TI  - [Autologous blood stem cell transplantation-current status and issues. Fukuoka
      Bone Marrow Transplantation Group].
AB  - Autologous blood stem cell transplantation (ABSCT) has been increasingly used in
      the treatment of malignant diseases. With the use of hematopoietic cytokines,
      collection of peripheral blood stem cell (PBSC) has become easier. Contamination
      of PBSC with tumor cells is supposed to be reflecting the amount of residual
      tumor cells in the host. G-CSF combined conditioning regimen seems to be
      effective for ANLL in complete remission (CR) probably by in vivo purging of
      residual leukemic cells. From our preliminary results, ABSCT can be used as the
      treatment of choice for standard risk ANLL, and aggressive non-Hodgkin's
      lymphoma. To clarify the curative potential of ABSCT, prospective clinical trial
      consisting of remission induction, consolidation of CR, PBSC harvests, and marrow
      ablative therapy for ABSCT will be required.

PMID- 7643447
TI  - [Recent progress in treatment and prophylaxis of graft-versus-host disease].
AB  - Graft-versus-host disease (GVHD) is one of major causes of mortality in
      allogeneic bone marrow transplantation (BMT). GVHD prophylaxis for HLA matched
      sibling BMT is widely done by methotrexate and/or cyclosporine. More intensive
      modalities are necessary for HLA mismatched related or HLA matched unrelated BMT;
      T cell depletion, ALG/ATG in preconditioning or following BMT and FK-506 with
      short term methotrexate are currently used with certain success. Moderate to
      severe GVHD may develop despite of these preventions, and standard to high dose
      of steroid with or without ALG/ATG is currently used as the first line therapy.
      GVHD, however, is an important component to cure malignant diseases through its
      anti-tumor effect called graft-versus-leukemia (GVL) effect. Several attempts
      have been made to induce mild to moderate GVHD both in allogeneic and in
      autologous BMT; low dose of cyclosporine, IL-2, ubenimex and donor buffy coat or
      peripheral lymphocyte transfusion are shown to be effective with some limitation.

PMID- 7643448
TI  - [Development of gene therapy using hematolymphopoietic cells].

PMID- 7643449
TI  - [The expression pattern of transcription factors (GATA, SCL) and biological
      characteristics in various leukemia cells].
AB  - We have studied gene expression of GATA-1, GATA-2, and SCL, which are known as
      cell-specific transcription factors, in 110 various leukemias consisted of 76
      patients with acute myeloid leukemia (AML), 19 with acute lymphoblastic leukemia
      (ALL), and 15 with chronic myeloid leukemia (CML) in blast crisis by the revearse
      transcription-polymerase chain reaction assay. Accordingly, we divided into three
      groups. Group I (GATA-1+SCL+): patients with AML exhibiting phenotypic
      characteristics of erythroid or megakaryocytic lineage and most of CML myeloid
      blast crisis were included. Group II (GATA-1+, SCL-): Not only CD7-positive and
      CD19-positive AML, but also a part of Ph+ALL demonstrated this pattern. Leukemia
      in this group is considered to have a capability to differentiate into myeloid
      and lymphoid lineages. Group III (GATA-1-, SCL-): patients in this group
      consisted of leukemias which are differentiated into specific cell-lineages,
      either myeloid or lymphoid, when compared to groups I or II. Our data suggest
      that the expression pattern of transcription factors reflects lineage potential
      in leukemia cells, leading to classification of leukemias.

PMID- 7643450
TI  - [WT 1 and leukemia].
AB  - The WT 1 gene has been isolated as a tumor suppressor gene of Wilms' tumor. Using
      reverse transcriptase-polymerase chain reaction (RT-PCR), relative levels of the
      WT 1 gene expression was examined in 87 patients with acute leukemia, 25 with
      chronic myelogenous leukemia (CML), and 24 with non-Hodgkin's lymphoma (NHL).
      Significant levels of the WT 1 gene were expressed in all leukemia patients, and
      for CML the levels increased as the clinical phase progressed. No point mutations
      were found in the WT 1 gene when samples from 15 acute leukemia patients were
      subjected to PCR single-strand conformation polymorphism analysis. In striking
      contrast to acute leukemia, the levels of WT1 gene expression for NHL were
      significantly low or even undetectable. The levels of WT 1 gene expression
      inversely correlated with the prognosis of acute leukemia. The quantification of
      the WT 1 gene expression made it possible to detect minimal residual disease
      (MRD) in acute leukemia regardless of the presence of absence of tumor-specific
      DNA markers. Simultaneous monitoring of MRD by RT-PCR using primers for specific
      DNA markers in four patients (two AML-M3 with PML/RAR-alpha, one AML-M2 with
      AML1/ETO, and one CML with bcr/abl) detected MRD comparable to that obtained from
      quantitation of WT 1 gene expression. In a patient with acute promyelocytic
      leukemia, the limits of leukemic cell detection by RT-PCR using either WT 1 or
      PML/RAR-alpha gene primers were 10(-3)-10(-4) and 10(-4) for bone marrow, and 10(
      5) and 10(-4) for peripheral blood, respectively.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7643451
TI  - [An animal model of leukemogenesis using transgenic mice].
AB  - The bcr/abl chimeric oncoprotein is considered to be implicated in the
      pathogenesis of Philadelphia chromosome-positive human leukemias. To investigate
      its biological function and the role in leukemogenesis in vivo, we generated
      transgenic mice expressing p210bcr/abl driven by the metallothionein promoter.
      Two of six founder mice and the transgenic progeny of one leukemic founder mouse
      developed leukemias several months after birth. Phenotypically, each leukemic
      mouse showed a thymic enlargement, a marked splenomegaly, and/or lymphnode
      swellings. Pathological examination revealed that leukemic cells were infiltrated
      in all tissues examined, especially in thymus, spleen, liver, and lymphnode.
      Expression of the p210bcr/abl transgene product and increased phosphorylation of
      cellular proteins in leukemic tissues were detected by the Western blot analysis.
      In addition, the expressed p210bcr/abl protein was demonstrated to possess an
      enhanced kinase activity by the in vitro immunecomplex kinase assay. These
      results indicate that hematopoietic precursor cells expressing the p210bcr/abl
      transgene product acquired a proliferative advantage and eventually developed
      leukemias in transgenic mice. The p210bcr/abl transgenic mice are considered to
      be an excellent animal model to investigate p210bcr/abl function and its role in
      leukemogenesis in vivo.

PMID- 7643452
TI  - [P-glycoprotein expression in hematological malignancies].
AB  - To clarify the common characteristics among P-glycoprotein (P-gp)-expressing
      hematological malignancies and whether chemotherapies could or could not induce P
      gp expression, we analyzed P-gp/MDR1 expression in tumor cells from 200 Japanese
      patients (104 with acute myeloblastic leukemia (AML); 30 with acute lymphoblastic
      leukemia (ALL); 66 with mature lymphoid malignancies). Functional P-gp expression
      was examined by Rhodamine-123 efflux test, and estimated with the data by RT-PCR
      method. In mature lymphoid malignancies, the cells of T or natural killer (NK)
      cell malignancies frequently expressed P-gp/MDR1. In AML, frequent P-gp/MDR1
      expression was associated with the expression of CD7 or c-kit and with 8; 21
      chromosomal translocation (p < 0.01), which were thought to be the
      characteristics of the hematopoietic stem cell. Though the expression of P
      gp/MDR1 was more frequent at onset than at relapse phase, the increase is thought
      to result from the expansion of blastic fraction expressing P-gp/MDR1. In ALL, P
      gp/MDR1 expression was not frequent in B-cell precursor lineage (three of
      eighteen patients), but the incidence was high in CD7(+) surface CD3(-) cases
      (seven of the cases). These results indicate P-gp/MDR1 expression is more
      frequently in the tumor of T, NK cell and stem cell, reflecting the
      characteristics of its normal counterpart.

PMID- 7643453
TI  - [Analysis of in vivo cell proliferation of ATL using SCID mice].
AB  - We made a model of in vivo cell proliferation of leukemic cells from adult T cell
      leukemia (ATL) patients using severe combined immunodeficient (SCID) mice. SCID
      mice injected with ATL cells from 6 of 8 ATL patients were found to have the
      tumor. DNA analysis revealed that the clone of the cells proliferating in mice
      was the same as that of the original leukemic cells. Histologic examination
      showed that the pattern of the infiltration of ATL cells in mice was similar to
      that of an ATL patient. Next, we examined the tumorigenicity of HTLV-I infected
      cell lines using SCID mice. Seven HTLV-I infected cell lines were injected into
      SCID mice and it was found that 4 of them were capable of proliferating in SCID
      mice. HTLV-I infected cell lines of non-leukemic cell origin could not engraft in
      SCID mice, indicating that these cells seemed not to have the enough genetic
      changes to acquire the tumorigenic potential. Analysis of gene expression
      suggested that neither IL-2 nor HTLV-I viral product was directly involved in the
      neoplastic cell growth of ATL. Furthermore, T cells immortalized by introduction
      of Tax could not engraft in SCID mice, indicating that the expression of tax gene
      seemed not to be sufficient for the neoplastic cell growth in vivo.

PMID- 7643454
TI  - [Allogenic bone marrow transplantation for Fanconi's anemia with leukemic
      transformation from an HLA identical father].
AB  - We report a case of a 19-year-old male with congenital aplastic anemia and
      multiple abnormalities; short stature, hypoplastic thumb, skin pigmentation and
      mental retardation. He was admitted to our hospital because of severe
      pancytopenia. Bone marrow aspiration showed markedly hypocellular marrow with 42%
      myeloblasts. He was diagnosed as AML (M2) transformed from Fanconi's anemia and
      underwent allo-BMT from an HLA-identical father. The conditioning regimen
      consisted of high dose Ara-C, high dose etoposide and 12Gy fractionated total
      body irradiation. Severe toxicity associated with the conditioning regimen was
      not observed. Cyclosporin A and short-term methotrexate were administered for
      prophylaxis of acute GVHD. Neither acute nor chronic GVHD were observed. He is
      well and free of disease for 15 months since BMT. Very few cases of Fanconi's
      anemia with leukemic transformation treated by BMT have been reported. Long-term
      observation will be necessary to evaluate our conditioning regimen for Fanconi's
      anemia with leukemic transformation.

PMID- 7643455
TI  - [Successful adjuvant therapy of M-CSF with chemotherapy of two cases of
      chemotherapy resistant acute promyelocytic leukemia].
AB  - We demonstrate two conventional chemotherapy-resistant cases of acute
      promyelocytic leukemia (APL) who were successfully treated with macrophage-colony
      stimulating factor (M-CSF). Case no 1 was a 40-year-old woman who was made
      diagnosis of APL on June, 1992, and treated repeatedly with a conventional
      chemotherapy, BHAC-DMP regimen, resulting in complete remission on October, 1992.
      After a couple of years, she had relapse with marked growth of APL cells in bone
      marrow. She was treated with BHAC-AMP and modified B-triple V but could not
      obtain remission. Case no 2 was a 36-year-old-man with APL who was treated with
      BHAC-DMP and BHAC-AMP and modified B-triple V therapy. These three conventional
      chemotherapy regimen were not effective for him. Eight million units of human
      native M-CSF was administered intravenously for 14 days after the last BHAC-AMP
      therapy in case no 1, and for 5 days after the last modified B-triple V therapy
      in case no 2. After the therapy, APL cells in peripheral blood or bone marrow of
      both patients disappeared completely and normal hemopoietic cells increased,
      obtaining in complete remission in both cases. These successful cases treated
      with M-CSF combining chemotherapy may suggest a new therapeutic strategy for APL
      in addition to all-trans retinoic acid.

PMID- 7643456
TI  - [MR angiography in the evaluation of endoscopic injection sclerotherapy for
      esophago-gastric varices].
AB  - We evaluated the utility of magnetic resonance angiography (MRA) for the
      detection of esophago-gastric varices and assessment of their therapeutic
      response to endoscopic injection sclerotherapy (EIS). MRA was performed in a
      total of 12 patients with esophago (E)-gastric (G) varices (V) (9 EV and 3 GV
      patients) both before and two-weeks after EIS. 25-35 horizontal images were
      obtained during single breath holding and data were reconstructed by using the
      two dimension time of flight method. MRA detected varicose lesions in all GV
      patients and in 7 of 8 EV patients of the grades F2 or higher. Varicose lesion in
      grade F1 EV patients were initially undetectable before EIS but became evident on
      MRA after EIS. The portal collaterals were equally well displayed by MRA and the
      superior mesenteric arteriography at its portogram phase. MRA and endoscopy were
      concordant for the disappearance or persistence of varicose lesions after EIS. We
      conclude that MRA is useful for the detection of esophago-gastric varices and
      other portal collaterals. MRA provides a non-invasive and workable technique in
      evaluation of patients with esophago-gastric varices undergoing EIS.

PMID- 7643457
TI  - [Correlation between tissue blood flow and tissue concentration of 5-FU and its
      metabolite in hepatic metastasis model for rats].
AB  - Correlation between 5-FU (20mg/kg) administrated via the peripheral vein and
      tissue concentration of its metabolite was studied in hepatic metastasis model
      prepared for rats. The measurement of tissue samples collected 30 min. after the
      5-FU administration suggested a possible negative correlation between the F-dUMP
      concentration and the blood flow in the normal hepatic tissue of the control
      group and the tumor tissue in the metastasis group. In administering 5-FU, a time
      dependent anticancer drug, to the tumor rich in the tissue blood flow, washing
      off effect of the drug by blood outflow cannot be neglected. Some device of
      prolonging the exposure time of anti-cancer agent to the tumor tissue will be
      necessary.

PMID- 7643458
TI  - [Effects of lactitol on fecal bacterial flora in patients with liver cirrhosis
      and hepatic encephalopathy].
AB  - Lactitol, a non-absorbable synthetic disaccharide, was administered at a dose of
      36g/day for 3-4 weeks to 8 patients with liver cirrhosis and hepatic
      encephalopathy in order to investigate its effects on fecal bacterial flora and
      clinical symptoms of hepatic encephalopathy. Lactitol significantly increased
      occupation ratio (ratio to total bacterial number) of anaerobic Bifidobacterium
      (before administration 7.1% --> after 4 weeks 46.0% (p < 0.05) as well as
      bacterial count of Lactobacillus. On the other hand, bacterial counts of
      Bacteroides and Clostridium, which are considered to be NH3-producing bacteria,
      and that of total aerobic bacteria were not markedly changed, but their
      occupation ratio were decreased after the administration. Further, tendencies
      toward decreased fecal pH, increased frequency of defecation and soft stools were
      observed. As for clinical efficacy, a decrease in blood ammonia concentration,
      improvement in mental state and flapping tremor were also observed.

PMID- 7643459
TI  - [Influence of splenectomy on drug therapy for acute liver failure induced by D
      galactosamine and lipopolysaccharide in rats].
AB  - We studied protective effects of dibutyryl cyclic AMP (DBcAMP 15 mg/kg i.p.) and
      OK-432 (5 KE/body), and the role of the spleen on D-galactosamine (D-Gal 500
      mg/kg i.p.) and lipopolysaccharide (endotoxin: Et 0.5 mg/kg i.p.) induced acute
      liver failure. The survival rates were 10% in the control group (D-Gal+Et), 53%
      in the group I A (DBcAMP was administered at 1 hour before D-Gal administration),
      79% in the group I B (Splenectomy was performed at 24 hours before D-Gal
      administration on the group I A), 87% in the group II A (OK-432 was administered
      at 24 hours before D-Gal administration), and 64% in the group II B (Splenectomy
      was performed at 24 hours before D-Gal administration on the group II A). GOT
      activities and TNF activities were significantly improved in the treatment
      groups, and in the group I B and group II A, they were more improved than in the
      group I A and group II B. In conclusion, spleen had the positive effect for OK
      432 treatment, and also had the negative effect for DBcAMP treatment on acute
      liver failure induced by D-Gal and Et.

PMID- 7643460
TI  - [Ultrasonic and laboratory studies on fatty liver in white-collar workers].
AB  - Ultrasonic and laboratory studies were performed in 816 white-collar workers over
      35 years old who received health examination. Prevalence of fatty liver diagnosed
      by ultrasonography was 17.9% in all subjects and was maximum (24.4%) in males 45
      49 years of age. Obesity index and body mass index were higher in fatty liver
      than in normal controls. Serum levels of glutamate pyruvate transaminase (GPT),
      cholinesterase, glutamate oxaloacetate transaminase (GOT), gamma-glutamyl
      transpeptidase (gamma-GTP), triglyceride, total cholesterol, uric acid, HbA1c and
      glucose were significantly higher, and a serum level of HDL-cholesterol was
      significantly lower in males with fatty liver than in controls with obesity.
      Prevalence of abnormal laboratory findings in fatty liver was also shown, and
      prevalence of fatty liver was prominently high in males with severe obesity or
      with mild elevation of GPT. A major cause of fatty liver was considered as
      obesity. In conclusion, fatty liver was a common cause of liver dysfunction and
      was closely related to risk factors for atherosclerosis especially in white
      collar workers.

PMID- 7643461
TI  - [Exacerbation of ulcerative colitis and chronic hepatitis by the treatment with
      interferon for chronic hepatitis B].

PMID- 7643462
TI  - [A case of Crohn's disease with a complication of thrombosis in the inferior vena
      cava].

PMID- 7643463
TI  - [Liver abscess and increased pulmonary permeability in Crohn's disease: report of
      a case].

PMID- 7643464
TI  - [A case report of heterochronic double cancer of the liver with type C liver
      cirrhosis].

PMID- 7643465
TI  - [A case of juvenile hepatocellular carcinoma arising from normal liver].

PMID- 7643466
TI  - [A case of hepatocellular carcinoma with invasion into the bile duct, difficult
      to differentiate from cholangiocellular carcinoma: observation by endoscopic
      retrograde cholangioscopy and peroral cholangioscopy].

PMID- 7643468
TI  - [Enhanced expression of fibronectin during cellular aging of endothelial cells
      and fibroblasts].

PMID- 7643467
TI  - [A case of non-icteric infiltrative carcinoma of the lower bile duct].

PMID- 7643469
TI  - [Arterial ageing of aorta and atherosclerosis--with special reference to
      elastin].
AB  - Ageing of the arterial wall is defined as the age-related structural and
      functional changes in arteries. These changes include distension of the lumen,
      kinking of the artery, and rigidity of the arterial wall. Distension of the
      arterial luminal diameter with hardening of the arterial wall causes chronic
      ischemia in peripheral tissues, leading to age-related deterioration of the
      organs. The ensuing pathological modification in blood circulation is mainly
      linked to the decrease in the elastic recoil of the arteries and to the
      increasing difficulty of pumping systolic blood volume towards the periphery.
      This results in increased systolic blood pressure in the elderly and an
      increasing load on the ageing heart. Age-related changes in elastic arteries are
      characterized as degenerative changes in the SMCs of the media associated with
      depositions of collagen fibers and the fragmentation of elastic fibers. Data
      obtained from in vivo experiments indicate that the susceptibility of aged
      arteries to atherogenic stimuli might be related to intrinsic cellular changes
      with age. Substances that can regulate the function of vascular wall cells may be
      continuously present in the vessel walls, perhaps as components of super
      extracellular matrix complexes. One type of substance is the functional domain
      structure of extracellular matrix molecules exposed to specific receptors or
      binding proteins on the surface of the cells. The role of extracellular matrices,
      especially elastin, on cultured vascular cells has been discussed.

PMID- 7643471
TI  - [Aging of aorta and atherosclerosis--role of nonenzymatic glycation of collagen].
AB  - In order to clarify the role of the nonenzymatic glycation of the collagen matrix
      in aging of the aorta and atherogenesis, we studied the relation between
      ketoamine or advanced glycation end-products (AGEs) and the solubility of
      collagen in human skin and aorta. AGEs were measured as a collagen-linked
      fluorescence (excitation wavelength: 370 nm. emission wavelength: 440 nm). There
      was a positive correlation between the level of AGEs and subjects' age in skin
      and aortic media. Collagen became more insoluble with increase in the amount of
      ketoamine and AGEs. Collagen was more resistant to pepsin digestion in
      atherosclerotic intima than in other tissues including aortic media, lesion-free
      intima and skin. Diabetic rats showed an accumulation of collagen in aortic media
      at 28 weeks after an injection of streptozotocin. Moreover, they increased the
      percentage of insoluble collagen to total collagen and the amount of AGEs binding
      to insoluble collagen in aortic media. In contrast, the amount of ketoamine of
      insoluble collagen was increased in diabetic rats at 16 weeks as compared to
      control. There was no difference in DNA contents of cultured smooth muscle cells
      between glycolaldehyde-modified and non-modified matrices. However, the activity
      of type I collagenase (inactive form) of smooth muscle cells decreased on
      glycolaldehyde-modified type I collagen as compared to that on non-modified
      collagen. These results suggest that AGEs contribute to the accumulation of
      collagen in atherosclerotic lesions and aged aorta through the insolubility of
      collagen and the inhibition of collagenase activity of smooth muscle cells.

PMID- 7643470
TI  - [Fibronectin and macrophage].
AB  - Monocyte-macrophages play a great part in atherogenesis. Interaction between
      macrophages and subendothelial-tissue including basement membrane and intima may
      play a critical role in atherogenesis. Therefore we examined the ability of
      macrophages to attach to various types of extracellular matrix proteins, which
      are the main components of these tissues. Adhesion of macrophages to fibronectin
      was remarkable compared to collagen. In addition we examined the effect of age on
      adhesion to fibronectin. Age-related increase in macrophage adhesion to
      fibronectin was found in vitro. It was also related to the concentration of
      surface receptors of macrophages which recognize the RGDS sequence within
      fibronectin (i.e. VLA5) during aging. Age-related increases in macrophage ability
      to attach to fibronectin may be related to atherogenesis during aging.

PMID- 7643472
TI  - [Elastic fiber and vascular function].

PMID- 7643473
TI  - [The survival rate of impaired glucose tolerance groups in the elderly].
AB  - We analyzed a total of 468 cases, all inmates of the Yokufukai Home for the Aged
      who had undergone a 50-gram oral glucose tolerance test (OGTT) from January 1980
      to December 1981 and who were followed up to the end of March 1994. All cases
      were divided into different normal, borderline and diabetic categories according
      to glucose tolerance. 1) Normal cases accounted for 39.6% of males and 39.2% of
      females, 50% and 52.5% were borderline cases in males and female and these were
      10.4% and 8.3% diabetic cases, respectively. 2) The overall survival rate of
      females was significantly higher than that of males groups (p < 0.05). 3) There
      was no significant difference in survival rate of males and females in the normal
      and impaired glucose tolerance groups (border and diabetic). CONCLUSION. Mildly
      impaired glucose tolerance could be considered as part of the normal aging
      process.

PMID- 7643474
TI  - [Clinical evaluation of myasthenia gravis in elderly patients].
AB  - In Japan, elderly patients who develop myasthenia gravis (MG) are increasing in
      number. However, there are few clinical reports concerning this issue. We
      evaluated the clinical manifestations, inducing or exacerbating factors,
      complications, treatments and prognosis of systemic MG in 11 patients older than
      60 years of age. Bulbar symptoms were more frequent in these patients compared
      with younger MG patients, and 6 out of 11 cases (54.5%) were mistakenly diagnosed
      as cerebrovascular disorders. Among inducing or exacerbating factors of MG were
      psychological problems inherently involved with the aged, physical factors, and
      inappropriate termination or rejection of medication. Increase in the level of
      anti-Ach-R antibodies was recognized in 10 out of 11 cases (90.9%). A high
      percentage of the patients had thymoma (36.4%) and thyroid diseases (45.5%): 3
      with Hashimoto's thyroiditis (27.3%), 1 with thyroid ophthalmopathy associated
      with hyperthyroidism, and 1 with simple goiter. Others were accompanied by
      ischemic heart disease, prostatic hypertrophy or stomach cancer. We treated these
      patients with corticosteroids, immunoglobulin, radiation for thymoma, or
      thymectomy in addition to administration of anticholinesterase agents.
      Prognostically, we found that duration of illness before death was shorter in
      those with onset later than 70 years of age. Seven out of 11 (63.6%) patients
      died of either aspiration pneumonia (4 cases), complications of thymectomy,
      congestive pulmonary edema or stomach cancer. There were no deaths associated
      with myasthenic crisis.

PMID- 7643475
TI  - [Asymptomatic atheromatous cerebrovascular diseases in patients with acute
      myocardial infarction--evaluation by brain magnetic resonance angiography].
AB  - To investigate the relationship between atherosclerosis in the cerebral and
      coronary arteries, we examined the prevalence of asymptomatic atheromatous
      cerebrovascular lesions in patients with acute myocardial infarction (AMI). The
      subjects consisted of 33 consecutive AMI patients with angiographically proven
      coronary artery stenosis/occlusion(s) who had no history of ischemic strokes, and
      33 age/sex matched controls without a history of coronary heart diseases or/and
      cerebrovascular diseases. Asymptomatic cerebrovascular lesions were evaluated by
      magnetic resonance angiography (MRA) with a 3-dimensional time-of-flight method
      within 2 months after the AMI onset. The evaluated arteries on MRA included the
      carotid bifurcation and the intracranial arteries (intracranial portion of the
      internal carotid artery, horizontal portion of the middle cerebral artery, and
      the basilar artery). Asymptomatic cerebrovascular stenotic lesions (more than 25%
      stenosis) on MRA were found in 8 AMI patients (24.2%) at the carotid artery
      bifurcation and 5 (15.2%) in the intracranial arteries, compared to 1 (3.0%) and
      3 (9.1%) respectively in control subjects. The lesions in the carotid bifurcation
      were significantly frequent in the AMI patients (p < 0.05), while those in the
      intracranial arteries did not differ between the two groups. The AMI patients
      with the intracranial artery lesions were significantly older than those without
      such lesions (p < 0.05). The data obtained indicates that the coexistence of
      asymptomatic atheromatous cerebrovascular diseases, especially the lesions in the
      carotid bifurcation, should be considered in treating patients with AMI. The
      older AMI patients, who may have not only extracranial lesions but also
      intracranial lesions, should be treated more carefully.

PMID- 7643476
TI  - [A case of bilateral infection-induced urolithiasis in a bed-ridden elderly
      female].
AB  - A 79-year-old bedridden female in whom bilateral small renal calculi were pointed
      nine months previously, presented with a high fever and non-specific abdominal
      symptoms. A diagnosis of bilateral renal and ureteral stones causing
      hydronephroureters with severe infection was made. She was referred to the
      urology department and treated with extracorporeal shock wave lithotripsy (ESWL).
      Persistent urinary tract infection caused by urease-producing bacteria, often
      seen in the bedridden elderly contributes to form infection-induced renal
      calculi. Such calculi are sometimes found in bilateral kidneys, can grow rapidly,
      and can often form with few, if any, symptoms. ESWL has been established as
      noninvasive treatment of choice for the great majority of upper urinary tract
      stones. All types of stones, including renal staghorn calculi, can be treated by
      ESWL with endourological support. Recurrence of stones after treatment is
      expected in approximately 40% of cases. In order to prevent recurrence, the stone
      should be removed totally and the patients must be observed carefully to keep the
      urinary tract totally free of infection.

PMID- 7643477
TI  - [Hepatitis C virus infection in elderly patients].

PMID- 7643478
TI  - Transforming growth factor-beta 1 induces morphological changes accompanied by
      extracellular matrix reconstitution in cultures of avian retinal pigmented
      epithelial cells.
AB  - The mechanisms of cell differentiation have been extensively studied with an
      avian retinal pigmented epithelial cell (PEC) culture system. Transforming growth
      factor-beta (TGF-beta) has been reported to have stimulatory or inhibitory
      effects on differentiation depending on tissue type. Although the mechanism by
      which TGF-beta exerts diverse effects is unknown, changes in the extracellular
      matrix (ECM) are believed to be related to the effects of TGF-beta. Therefore,
      the effects of TGF-beta 1 on the cellular morphology and the distribution of ECM
      components such as laminin, tenascin, fibronectin, and types I and IV collagens
      were investigated in confluent cultures of differentiated PECs during a period of
      6 days. We found that differentiated PECs with polygonal morphology and pigmented
      granules changed to pleomorphic and less pigmented cells 4 days after the
      addition of TGF-beta 1. These changes were preceded by changes in the
      distribution of ECM components, particularly laminin and tenascin after 2 days.
      The effects of TGF-beta on the differentiation of PECs are discussed.

PMID- 7643479
TI  - Histological and histochemical studies of the normal and faulty closure of the
      embryonic fissure in the eye of ICR mouse.
AB  - Histological and histochemical studies were carried out in Jcl:ICR mice to
      determine the changes in microscopic structures and glycosaminoglycan molecular
      species in the tissues involved in normal or faulty closure of the embryonic
      fissure. The purpose of this study was to elucidate the mechanism underlying the
      faulty closure of the embryonic fissure and to identify the key substances
      involved in normal and faulty closure. To obtain mice with an appropriate faulty
      closure of the embryonic fissure, ochratoxin A was employed as a teratogenic
      agent. Serial sections from tissues undergoing normal and faulty closure of the
      embryonic fissure were cut at a right angle to the fissure. As the staining
      procedures, a hematoxylin-eosin procedure and a sensitized high iron diamine
      method were used. A chemical modification (nitrous acid treatment) or an enzyme
      digestion procedure (chondroitinase ABC digestion procedure) was employed in
      combination with the sensitized high iron diamine method to identify the
      glycosaminoglycan molecular species in the tissues. The results obtained in the
      present study have substantiated the histophysiological importance of
      glycosaminoglycan molecular species during the course of histogenesis in the
      normal and the faulty closure of the embryonic fissure of developing murine eyes.

PMID- 7643480
TI  - Expression of distribution of alpha 2,3-sialyltransferase mRNA in rat cornea.
AB  - The glycocalyx, present on the surface of the corneal epithelium, contains
      sialoglycoconjugates. The developmental change in the sialylated residues may be
      evaluated by examining the expression of the sialyltransferase mRNA. We examined
      the distribution of Gal beta 1,3GalNAc alpha 2,3-sialyltransferase mRNA in rat
      corneas during development using in situ hybridization histochemistry to detect
      the starting point of the synthesis of O-linked sialoglycoconjugates. Eyelid
      opening occurred between postnatal days 14 (P14) and 16 (P16). In the corneal
      epithelium, little hybridization signal was observed until P12, whereas distinct
      hybridization signals were identified at P14 and thereafter. The expression of
      alpha 2,3-sialyltransferase mRNA is developmentally regulated, based on the
      programmed time-course of the gene expression, and the corneal epithelium may
      start to synthesize O-linked sialoglycoconjugates prior to the critical eyelid
      opening stage.

PMID- 7643481
TI  - Inhibition of corneal ulceration by tetrapeptidyl hydroxamic acid.
AB  - The inhibitory activity of a new peptidyl collagenase inhibitor, FN-439 or
      tetrapeptidyl hydroxamic acid (H2N-C6H4-CO-Gly-L-Pro-D-Leu-D-Ala-NHOH), was
      determined against vertebrate collagenases derived from human fibroblast, human
      polymorphonuclear leukocyte (PMN) and tadpole skin. In addition, the effect of FN
      439 in inhibiting corneal ulceration was also investigated with alkali-burned
      rabbit corneas. FN-439 can block the active site of collagenase, and hydroxamic
      acid can chelate Zn2+ which is essential for collagenase activity. Furthermore,
      this compound contains D-amino acids to resist nonspecific host-derived
      degradative enzymes. In our experiments, corneal ulceration occurred in 5 of the
      9 control eyes, but in none of the 9 eyes treated with FN-439 (P < 0.01). The
      only cellular elements observed at the ulcerated area were PMNs and monocytes. FN
      439 appeared to act against PMN collagenase. In addition, we compared the change
      in the concentration of FN-439 (D-peptide) and the L-form of FN-439 (L-peptide)
      in aqueous humor aspirated from the rabbit eyes burned with alkali. After
      incubation for 3 hours, the concentration of the D-peptide was decreased by 3%,
      while that of the L-peptide was decreased by 60%. FN-439 may be useful for
      treating noninfectious corneal ulcers because of its potent activity (IC50 = 1
      microM) and chemical and biological stabilities.

PMID- 7643484
TI  - Association of acquired color vision defects in blue cone monochromatism.
AB  - The retinal functions of a 43-year-old man with diabetic retinopathy in a family
      affected by blue cone monochromatism were studied. While changes in visual acuity
      and color vision were similar to those seen in patients affected by rod
      monochromatism, and his spectral sensitivities on high intensity background and
      his threshold versus intensity curve indicated only suggestive blue cone
      function, mass electroretinograms (ERG) findings demonstrated well preserved blue
      cone function. The disparity in blue cone function between psychophysical and
      mass electroretinographical evaluation may be caused by the difference in how
      much the fovea influenced each testing. Diabetic retinopathy most likely caused
      significant reduction of the psychophysical blue cone function and resulted in
      clinical findings similar to rod monochromatism. The mass blue cone ERG was
      useful to differentiate blue cone monochromatism from rod monochromatism in this
      diabetic patient.

PMID- 7643483
TI  - Circadian rhythms in aqueous protein concentration and intraocular pressure in
      rabbits.
AB  - Circadian rhythms in aqueous protein concentration (APC) and intraocular pressure
      (IOP) were examined in Dutch rabbits using the laser flare-cell meter and a
      pneumatonometer. The reproducibility and seasonal changes in circadian rhythm
      were also investigated. Rabbits were trained to a lighting cycle of 12-hour light
      and 12-hour darkness. The mean value of reproducibility coefficients obtained
      with re-examination at 2-week intervals was 21.9% in the reading of the laser
      flare-cell meter. APC was reduced during the dark phase, and increased rapidly
      and remained high during the light phase. On the other hand, IOP showed an
      inverse circadian rhythm which was negatively correlated with that of APC. The
      total average of APC throughout 24 hours was 39.1 +/- 28.3 (mean +/- SD) mg/100
      ml equivalent of bovine serum albumin, which agreed with the previous data.
      Seasonal changes in circadian rhythm were not statistically significant either in
      APC or in IOP.

PMID- 7643482
TI  - Effects of local hypothermia on uveal blood flow and postoperative inflammation
      in vitrectomy.
AB  - Effects of local hypothermia on uveal blood flow and postoperative inflammation
      were evaluated in experimental vitrectomy in albino rabbits. Solutions used for
      intraocular perfusion were maintained at 9 degrees C, 22 degrees C or 37 degrees
      C. Following closed vitrectomy, the vitreous cavity was irrigated for 60 minutes.
      Temperatures at various sites and uveal blood flow were measured before and
      during the procedure. Aqueous protein concentrations were checked on
      postoperative days 1, 7 and 14. There was a larger decrease in temperature at the
      retina than at the choroid or the ciliary body. Blood flow at the ciliary body
      was reduced to 76.0% and that at the choroid to 77.0% of the preoperative level
      after 60 minutes of irrigation at 9 degrees C. The decrease was 91.0% and 88.3%,
      respectively, after 60 minutes of irrigation at 22 degrees C. Aqueous protein
      concentrations in the 9 degrees C and 22 degrees C groups were significantly
      lower than those in the 37 degrees C group on the first postoperative day in the
      eyes irrigated for 60 minutes. In the eyes irrigated for 30 minutes, however, no
      significant differences were seen. Local hypothermia during prolonged vitrectomy
      seems to decrease inflammation in the early postoperative stage.

PMID- 7643485
TI  - Influence of myopic refraction on visual field defects in normal tension and
      primary open angle glaucoma.
AB  - It is known that the prevalence of normal tension glaucoma (NTG) or primary open
      angle glaucoma (POAG) is higher in the myopic population and that the prevalence
      of myopia and NTG is higher in Japan than in western countries. To evaluate the
      influence of myopic refractive error in the central 10 degrees of the visual
      field in NTG eyes, the data obtained from NTG eyes with the Humphrey Visual Field
      Analyzer were analyzed in comparison with data from POAG eyes. One hundred and
      twenty eyes of 86 NTG patients and 197 eyes of 138 POAG patients whose ages were
      65 years or younger were included in this study. All of them had clear ocular
      media, refractive power less than +1.0 diopter and no myopic degeneration in the
      fundus. Multiple linear regression analysis was performed with the dependent
      variable of the deviation of the measured threshold value from the normal
      reference value (TD; STATPAC 2), and independent variables of myopic refractive
      power and the mean deviation (MD; STATPAC 2) as an index of the disease stage at
      each test point of the Humphrey 10-2 program and at the most central 12 test
      points of the 30-2 program. Myopic power was found to have a significant positive
      correlation with the depression in the lower cecocentral area in both NTG and
      POAG eyes, while only in NTG eyes it had a significant negative correlation with
      the depression in the upper arcuate area extending just nasal to the fixation
      point.

PMID- 7643486
TI  - Metastatic orbital tumors.
AB  - A review was made of the clinical data of 28 patients with metastatic orbital
      disease diagnosed in our clinic between 1972 and 1993. Fifteen were men and 13
      were women. The average age at diagnosis was 58.7 years. The right orbit was
      involved in 12 and the left orbit in 14 cases. Two cases had bilateral orbital
      involvement. Breast carcinoma was the most frequent tumor (8 of 28, 28.6%)
      followed by neuroblastoma (7 of 28, 25.0%), lung carcinoma (6 of 28, 21.4%),
      prostate carcinoma (3 of 28, 10.7%), gastrointestinal carcinoma (2 of 28, 7.1%),
      renal cell carcinoma and thyroid carcinoma (1 of 28, 3.6% each). Proptosis
      (67.9%), motility disturbance (57.1%) and mass (50.0%) were the three most common
      presenting signs. Enophthalmos was noted in two cases with breast carcinoma. Nine
      cases presented with ophthalmic signs and metastatic tumor was recognized later.
      In the remaining 19 cases, the diagnosis of the primary tumor preceded the onset
      of orbital metastasis. The time interval between the detection of the primary
      malignancy and metastatic orbital tumor was shortest for lung carcinoma (mean: 2
      months) and longest for breast carcinoma (mean: 34 months). Radiotherapy and
      chemotherapy were applied in 12 cases. Improvement in orbital signs and visual
      acuity was noted in 5 cases. Radiotherapy, chemotherapy and hormonal therapy were
      used in 8 patients and improvement in orbital signs was noted in 4 of these
      patients. Four of 28 patients (2 with breast carcinomas, one with prostate
      carcinoma and one with thyroid carcinoma) survived longer than 5 years.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7643487
TI  - Posterior sub-Tenon injections of repository corticosteroids in uveitis patients
      with cystoid macular edema.
AB  - Repository corticosteroid was injected into the posterior sub-Tenon space in 29
      cases (39 eyes) of cystoid macular edema (CME) secondary to uveitis. There were
      12 cases of Behcet's disease, 7 cases of sarcoidosis, one case of tuberculous
      uveitis, and 9 cases of etiology unknown uveitis. In some of the patients
      injections were repeated 2 to 7 times at intervals of more than 2 weeks. Twenty
      two of the 39 treated eyes (56.4%) showed visual improvement in at least two
      lines of visual acuity. Fifteen of the 22 eyes had maintained improved visual
      acuity over 6 months. Eleven eyes showed no improvement in vision. Most of them
      already had poor visual acuity (0.2 or less) before the injections. Complications
      of the treatment included cataract in 6 eyes, glaucoma in one, and blepharoptosis
      in one. Injection of repository corticosteroids into the posterior sub-Tenon
      space is of value in the treatment of CME secondary to uveitis. However, we have
      to beware of the complications of treatment.

PMID- 7643488
TI  - Myxoma of the conjunctiva: a case report and a review of the literature.
AB  - A rare case of conjunctival myxoma is reported. A painless tumor was noted in the
      left bulbar conjunctiva of an 80-year-old woman. The extirpated tumor, 12 x 10
      mm, was hypocellular and composed of spindle-shaped or stellate tumor cells. The
      tumor stroma showed extensive myxomatous changes. Alcian blue stain with
      hyaluronidase digestion revealed that the matrix contained rich amounts of
      hyaluronidase-sensitive acid mucopolysaccharides. Immunohistochemically, the
      tumor cells were positive for vimentin and alpha-smooth muscle actin, suggesting
      a fibroblastic or myofibroblastic cell phenotype. A review of the literature
      revealed the rare incidence and invariable benign behavior of conjunctival
      myxoma.

PMID- 7643489
TI  - Posterior tenotomy of the superior oblique at the scleral insertion for A-pattern
      deviations.
AB  - A posterior (two-thirds) tenotomy of the superior oblique at the scleral
      insertion spares the anterior fibers whose action is primarily torsional and can
      avoid some complications such as cyclovertical diplopia or torticollis, which may
      be induced by a superior oblique tenotomy or a recession for A-pattern deviations
      associated with superior oblique overaction (SOOA). A retrospective review was
      performed of 11 cases with A-pattern, aged 5 to 51 years, who underwent the
      posterior tenotomy. The average preoperative A-pattern was 18.3 prism diopters
      and the posterior tenotomy resulted in 16.3 prism diopters of reduction in the A
      pattern. There was a good coefficient of correlation between the preoperative
      amount of A-pattern and the obtained reduction in it (P < 0.001). SOOA was graded
      on a 9-point system. The average SOOA score of our cases was reduced from +2.77
      to +0.77 after the surgery. None of the cases showed worsening of stereoacuity or
      cyclodeviation. The posterior tenotomy is a simple and effective procedure to
      correct mild to moderate A-pattern deviations with SOOA.

PMID- 7643491
TI  - Clinical features of Japanese Leber's hereditary optic neuropathy with 11778
      mutation of mitochondrial DNA.
AB  - The G to A transition of nucleotide position (nt) 11778 of mitochondrial DNA
      (mtDNA) has been frequently observed in Japanese Leber's hereditary optic
      neuropathy (LHON) cases. Therefore, we performed a multi-institutional study in
      Japan of LHON cases with this 11778 mutation of the mtDNA. Genetic and clinical
      data on 108 cases (90 affected and 18 carriers) in 79 unrelated families were
      obtained from 64 Japanese institutions. Detection of the nt11778 mutation was
      performed using restriction enzymes (74 cases) or dot blot with allele specific
      oligonucleotide (34 cases). Heteroplasmy was observed in 13 of the 90 affected
      cases and in 8 of the 18 carrier cases. Forty-five families had family history of
      LHON (44 maternal inheritance, 1 undetermined), and in 28 families (35.9%) there
      were isolated cases. The male-to-female ratio in the affected was 82:7 (92.1%
      male). The age at onset of visual loss ranged from 7 to 59 years (average: 23.4
      years). All cases had bilateral involvement except one case with a blind eye
      resulting from ocular infection during childhood. Onset interval between the two
      eyes ranged from simultaneous to 17 months (average: 2.5 months), in 91.3% of
      cases being under 6 months. Visual acuity was 0.1 or worse in 152 (85.9%) of 177
      eyes, only 6 eyes showing over 0.5. Progression of visual loss ranged from 0 to
      48 months (average: 6.2 months). Central visual field abnormality was observed in
      162 eyes (96.4%) of 168 eyes. Nonsuspect fundus in the ophthalmoscopic
      examination constituted 22.8% of eyes. Systemic corticosteroid was given to 45
      (52.9%) of 85 cases and visual acuity was improved in only 2 cases (4.4%).
      Arrhythmia, neurological and muscular abnormality were observed as rare general
      complications. The present survey indicates that the male-to-female ratio is
      higher than the previous Japanese LHON statistics and that the visual outcome is
      better than in American LHON cases with the 11778 mutation.

PMID- 7643490
TI  - Histopathological study of microspherophakia in the Weill-Marchesani syndrome.
AB  - A surgically obtained lens from a 66-year-old man with the Weill-Marchesani
      syndrome was examined histopathologically by light microscopy, transmission
      electron microscopy and scanning electron microscopy. The lens was diffusely
      opaque and brown. It was microspherophakic in appearance, 6.0 mm in equatorial
      diameter and 4.8 mm in anteroposterior diameter. The lens fibers were well
      preserved, and ran circularly in the cortex and elliptically in the fetal
      nucleus. The lens fibers had undergone hyaloid degeneration in the area from the
      deep cortex to the superficial portion of the adult nucleus. Hyaloid degeneration
      also extended from the anterior to the posterior pole and was more marked in the
      equator. The distribution of lens fibers suggested that microspherophakia had
      developed postnatally. It is surmised that later changes in the shape of the lens
      affected the lens fibers, inducing hyaloid degeneration.

PMID- 7643493
TI  - [Valvuloannuloplasty for atrioventricular valvular regurgitation in complicated
      cyanotic cardiac anomalies].
AB  - Valvuloannuloplasty for atrioventricular (AV) valvular regurgitation was
      performed in 13 patients with univentricular AV connection and double outlet
      right ventricle. The suturing-up of free margins of the anterior and posterior
      common leaflets, which divides the common orifice into two parts, was performed
      in 4 children with quadricuspid or quintacuspid common AV valve and effectively
      reduced the regurgitation. The semicircular annuloplasty with a thin GORE-TEX
      graft was carried out in two patients having tricuspid AV valve, and a favourable
      result was obtained. In bicuspid AV valvular regurgitation, two patients received
      the suturing-up of free margins of prolapsed leaflets, and the results were
      satisfactory. From these results we consider that the semicircular annuloplasty
      for dilated tricuspid AV valve and the suturing-up of free margins of dilated or
      prolapsing leaflets in quadricuspid or quintacuspid and bicuspid AV valves are
      the recommendable procedures. If more than mild AV valvular regurgitation
      remained after these valvuloplasties, the Kay's and/or DeVega's annuloplasties
      should be added for eliminating the regurgitation.

PMID- 7643492
TI  - [Surgical results of valvuloplasty for common atrioventricular valve
      regurgitation in single ventricle].
AB  - From 1988 through 1994, 18 patients who had common atrioventricular valve
      regurgitation associated with single ventricle underwent valvuloplasty. All
      patients had isomerism heart (right isomerism: 16, left isomerism: 2). The
      preoperative degree of regurgitation was 3.3 +/- 0.4 (Sellers). Valvuloplasty was
      performed by two different procedures. Semi-circular annuloplasty was used in
      nine patients. Dividing the common atrioventricular valve orifice into two parts
      (bivalvation) with or without annuloplasty was used in nine. The concomitant
      procedures varied: three patients underwent systemic pulmonary shunt, two
      underwent repair of total anomalous pulmonary venous drainage, one underwent
      pulmonary arterial banding, five underwent bidirectional Glenn, shunt, and four
      underwent Fontan operation. One early death and three late deaths have occurred.
      The early postoperative degree of regurgitation was reduced to 1.3 +/- 1.0. In
      nine patients, however, the degree of regurgitation increased late
      postoperatively. Seven patients were reoperated on because of regurgitation:
      three patients had valve replacement and four had reannuloplasty. Increased
      incidence of deterioration of regurgitation in late period was seen in patients
      under 2 years old and those receiving a concomitant Blalock shunt. Lower event
      free rate after 2 years was seen in patients with double inlet right or
      indeterminate ventricle and those underwent the annuloplasty alone. We conclude
      that the dividing common atrioventricular valve orifice into two parts with
      annuloplasty could effectively reduce the regurgitation in most patients with
      isomerism heart, and the concomitant ventricular unloading operation seems to
      offer promise for improving long-term results.

PMID- 7643494
TI  - [Valvulo-and annuloplasty in correction of complete atrioventricular septal
      defect].
AB  - The surgical and postoperative long-term results were assessed in 55 patients
      undergoing correction of complete atrioventricular septal defects. The patients
      was divided into two groups according to mode of plasty of the atrioventricular
      valve: 45 patients in whom the cleft was closed in the earlier series, and 10
      with trifoliated mitral valve, leaving the cleft unclosed in the later series.
      The early death occurred in 13 of 45 patients in the earlier series and none in
      the later series. During 11 years follow up period, mitral valve regurgitation of
      grade 3 and 4 was observed in 20% of the patients, respectively, in the earlier
      series. In contrast, grade 3 mitral regurgitation was detected in only one and no
      grade 4 regurgitation was present in the later series. Tricuspid valve
      regurgitation was irrelevant. In the later series, the diameter of the mitral
      valve was greater than the average value of Rowlatt's standard by 3.4 mm after
      partisioning the common atrioventricular valve into mitral and tricuspid
      components, and smaller than the normal by 0.2 mm, though the diameter was within
      the normal range after valvulo-and annuloplasty. On the other hand, the diameter
      of the tricuspid valve was also greater than the normal value by 1.7 mm after
      partisioning, however, that was smaller than the normal by 1.7 mm after valvulo
      and annuloplasty, on the average. The diameter was smaller than the normal lower
      limit by one standard deviation in two patients. There was present neither mitral
      nor tricuspid stenosis in all on the post-operative hemodynamic study.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7643496
TI  - [Reconstructive techniques for complete mitral valve repair for mitral valve
      insufficiency].
AB  - Reconstruction of mitral valve, which was performed completely, provides better
      postoperative ventricular function and less morbidity compared with prosthetic
      replacement. In this article, reconstructive techniques as a radical mitral valve
      repair are demonstrated from a viewpoint of long-term performance. Since January,
      pure mitral regurgitation due to prolapse were repaired with freedom from
      reoperation of 89% at 5 years and 81% at 10 years. The incidence rate of
      thromboembolism was 0.8% and no endocarditis or hemorrhagic complications were
      noted. The technique of leaflet resection-suture is most useful and reliable for
      the mural leaflet prolapse, and replacement of chordae tendineae is appropriate
      for the diffuse anterior leaflet prolapse. Prosthetic ring implantation increase
      leaflet coaptation, reinforce sutures and prevent further annular dilatation.

PMID- 7643495
TI  - [Surgical repair of complete atrioventricular septal defect: annuloplasty by
      using a smaller VSD patch].
AB  - Recent policy for the intracardiac repair of complete atrioventricular septal
      defect (CAVSD) is demonstrated on the basis of the following theoretical
      background. In the normal heart, the originating portion of the ascending aorta
      and the crux intrude between the mitral and tricuspid orifices each from the
      anterior and from the posterior, separating both the orifices together with a
      short fibrous septal junction. In CAVSD, however, the common A-V orifice takes an
      elliptic form without any septal junction. It is considered beneficial,
      therefore, to surgically produce a short septal junction by using a smaller patch
      to close the ventricular portion of the AVSD. When the left lateral leaflet is
      larger, two leaflets valve plasty is suggested and when it is smaller, three
      leaflets valve plasty is suggested to reconstruct the left-sided A-V valve,
      although competence of the valve leaflets must be finally secured by doing
      repeated water injection tests. The size of the orifices of the reconstructed
      left-sided as well as right-sided A-V valve should also be confirmed not to be
      stenotic by using Hegar sizers. Since 1991, we have applied this surgical concept
      in 7 patients with CAVSD. Postoperatively, there was no left A-V valve
      regurgitation in one and slight regurgitation remained in 6 patients. The result
      is considered to be satisfactory. Although one patient died due to PH crisis, the
      cause of death was not related to valve regurgitation.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7643498
TI  - [Operative procedures for mitral prolapse and its clinical results].
AB  - Mitral valve plasty is the very important procedure for treatment of mitral
      regurgitation from the view point of post operative quality of life because
      patients may be possible to be free from postoperative drug therapy especially
      when the normal sinus rhythm is restored even if the concomitant maze procedure
      is necessary. In this report, 36 patients who underwent mitral valve plasty for
      mitral regurgitation were evaluated. In 18 patients who had posterior leaflet
      prolapse, McGoon's procedure was performed. Two of them required secondary mitral
      valve replacement 4 days after operation. Reoperation disclosed tissue detachment
      at the mitral annulus sutures which were not reinforced by a ring. It was
      considered that annular ring plasty is preferable after resection of prolapsed
      posterior leaflet by McGoon's procedure. Out of 18 patients who had mitral valve
      prolapse including anterior leaflet, 8 patients underwent such conventional
      procedures as transfer of chordae tendinae, leaflet resection and shortening of
      chordae. Four patients resulted in second look mitral valve replacement 11 days
      to 1 month after mitral valve plasty. On the contrary, the clinical results of
      repair of chordae tendineae with artificial chordae of extended
      polytetrafluoroethylene (ePTFE) were good. It is concluded that the resection of
      prolapsed leaflet and reconstruction of the annulus with reinforcement using a
      prosthetic ring is preferable for the posterior leaflet prolapse. For the
      anterior leaflet prolapse, good results can be obtained by replacement of chordae
      tendineae with ePTFE sutures.

PMID- 7643497
TI  - [Mitral valve plasty for better long term results].
AB  - Between July 1991 and January 1995, 74 patients with pure mitral valve
      regurgitation (MR) underwent mitral valve plasty (MVP) at out institute. Our
      procedure includes chordal replacement of the anterior leaflet with PTFE sutures
      (42 patients). There were one hospital death (1.4%) and two late deaths (2.7%) in
      this series. Only 2 patients (2.7%) needed valve replacement after unsatisfactory
      repair during the same operation. Late postoperative doppler echocardiographic
      study (mean follow-up, 12.0 months) showed less than mild regurgitation in 66
      patients (95.7%) of 69 patients who are alive. In April 1993 we decided to
      complete the repair with no or only trivial regurgitant flow by intraoperative
      transesophageal echodoppler study (TEE). The results have remarkably improved.
      Late postoperative echodoppler study revealed less than mild reguritant flow in
      all 49 patients having undergone mitral valve repair with no or trivial
      regurgitation by intraoperative TEE. It is clear than the TEE study has
      contributed to the better quality of mitral valve plasty, and we believe that it
      is important for better long term results to complete mitral valve plasty with no
      or only trivial regurgitant flow.

PMID- 7643499
TI  - [The experience of mitral valve repair for valve regurgitation].
AB  - Between November 1993 and March 1995, 10 patients underwent mitral valve repair.
      Six of them were performed with McGoon's procedure for prolapsed posterior
      leaflet. Two of them were performed chodal reconstruction with PTFE sutures for
      prolapsed anterior leaflet. A patient received McGoon's procedure of posterior
      leaflet and chodal reconstruction of anterior leaflet. A patient of ischemic
      mitral regurgitation underwent mitral annuloplasty. There were no operative and
      late deaths. The MR disappeared or improved to grade I in 9 patients. A patient
      with McGoon's procedure had hemolytic anemia and required reoperation.

PMID- 7643500
TI  - [Reconstructive surgery for mitral valve regurgitation in 64 patients:
      postoperative results of each different type of surgical methods].
AB  - Between January 1981 and November 1994, 64 patients underwent reconstructive
      surgery for mitral valve regurgitation (MR). The ages of the patients ranged from
      18 to 71 years (52.8 +/- 8.9). Pathological causes of regurgitation were
      degenerative in 41 (64%), infective endocarditis in 9 (14%), rheumatic in 8 (13%)
      and ischemic in 6 (9%). In 27 patients, Kay's and Reed's methods were performed
      for prolapsed valve and enlarged annuls. In 23 patients who had ruptured chordae
      of the anterior leaflet in 3, posterior leaflet in 17 and both anterior and
      posterior in 3, McGoon's method was performed. Ten patients, who had elogated
      chordae or ruptured papillary muscle, were repaired with GORE-TEX sutures. Cleft
      repair with sutures and leaflet repair with autopericardium patch was done in 4
      patients. There was no hospital death, but one late death. With the follow-up
      interval from 2 to 155 (mean 63.2) months after surgery, the incidences of
      freedom from reoperation were 94.8% after McGoon procedure, 89.7% after Kay and
      Reed, 88.9% after chordaplasty and 75% after cleft and patch repair. The
      hemodynamics and left ventricular function after McGoon repair in 15 patients
      revealed with significantly better outcomes than after valve replacement in 15
      patients. In conclusion, optimal selection of reconstructive procedures will
      offer satisfied postoperative long-term results with less freedom of reoperation
      for MR.

PMID- 7643501
TI  - [Repair of mitral valve prolapse by resection and sliding plasty].
AB  - There have been many techniques applied to the repair of mitral valve prolapse,
      and the method used in a particular case is usually selected according to the
      position and extent of the lesion. To simplify and standardize the technique of
      mitral valve repair, we have adopted the resection, sliding plasty and ring
      annuloplasty methods since December 1992. Of 10 consecutive surgical cases, 2
      involved prolapse of the anterior leaflet, 1 the posteromedial commissural, and 7
      the posterior leaflet. One patient with posterior leaflet prolapse required valve
      replacement due to dehiscence of the plastied site on the 3rd postoperative day,
      and one died because of sepsis. However, the remaining patients were doing well
      without mitral regurgitation at a mean of 20 months (range: 8-32) after the
      operation. The advantages of these techniques include easy adjustment of the
      height of the leaflet and a good chance of long-term durability, since the
      affected lesion is resected.

PMID- 7643502
TI  - [Mitral valve repair for mitral regurgitation].
AB  - In these 14 years, 54 adult patients, 28 males and 26 females, mean age 49.6
      years old, underwent mitral valve repair for mitral regurgitation. Valve lesion
      consisted of 28 valve prolapse, 23 torn chordae, 4 ischemic lesion, 3 rheumatic
      changes, and 3 clefts. Valve prolapse near the commissure was repaired by Kay
      Reed's annuloplasty in 31 patients. Torn chordae of the posterior leaflet was
      repaired by quadrangular resection of the leaflet in 21 cases. Commissural valve
      prolapse by torn chordae was treated by commissural resection and sliding repair
      of the leaflet in 5 patients. Torn chordae of the anterior leaflet was repaired
      by small triangular resection of the leaflet with artificial chordae using ePTFE
      suture or transfer of posterior chordae to the anterior leaflet in 6 cases. Ring
      annuloplasty was performed in 21 cases. Postoperative echocardiographic
      examination revealed no regurgitation in 41 patients, mild MR in 10, and moderate
      MR in 3. One patient died of arrhythmia early postoperatively. Another patient
      had cerebral infarction 10 months after the operation. No other complication or
      no late death was experienced. CONCLUSIONS: Early and late results of mitral
      valve repair for mitral regurgitation was satisfactory. Better long-term results
      will be expected by the improvement of surgical technique.

PMID- 7643503
TI  - [The effect of mitral valve repair and postoperative mitral valve function].
AB  - Thirty-six patients who underwent mitral valve repair were analyzed to evaluate
      the effect of mitral valve reconstructive technique. The final aim of this
      technique is to true up the coaptation line of both leaflets. Resection and
      reconstruction of the leaflet was performed on anterior leaflet in 11, on
      posterior leaflet in 12, and on both leaflets in 5. The newly contrived wrapping
      and shortening chordoplasty was performed on anterior leaflet in 6, on posterior
      leaflet in 3, and on both leaflets in 2. Two patients had replacement of
      artificial chordae tendinae with EPTFE suture. Commissuroplasty was performed at
      anterolateral commissure in 5, at posteromedian commissure in 15, and at both
      commissures in 5. Thirty patients with dilated annulus underwent ring
      annuloplasty with Carpentier ring. LVEDVI and LVESVI significantly decreased
      after mitral valve repair, and left ventricular volume overload was markedly
      reduced. Mitral valve orifice area was 3.23 +/- 1.14 cm2 and did not show the
      sign of mitral stenosis after repair. Left ventricular pressure volume area,
      which reflects the oxygen consumption of the myocardium, was markedly reduced
      after successful mitral repair.

PMID- 7643504
TI  - [Reconstructive surgery for acquired mitral regurgitation].
AB  - Between December, 1967, and July, 1994, 96 patients underwent repair of the
      mitral valve for acquired mitral valve regurgitation. According to Carpentier's
      classification, mitral valve pathology resulting in valve regurgitation was
      classified into three types; 4 patients assigned to type I, 63 type II, and 29
      type III. The operative mortality rate was 1.0%. Follow-up data were available in
      95 patients from 0.5 year to 25.3 years (mean average 8.8 years). The late
      mortality rate were not different between patients with valve pathology of type
      I, II and those with valve pathology of type III. Thromboembolism occurred on
      three patients for an embolic rate of 0.4% per patient-years. Twenty-eight
      patients required reoperation for residual MR and dehiscence of suture lines
      (type II; 10 cases, reoperation-free rate at 20 years, 83.2%) or recurrent MR due
      to progression of valve deformity (type III, 18 cases, reoperation-free rate at
      20 years, 14.8%). These results demonstrate that patients with type I and II
      valve are good candidates for MVP, and that high incidence of reoperation for
      recurrent MR may limit the application of MVP to selected patients with type III
      valve.

PMID- 7643505
TI  - [A case of mitral valvuloplasty with concomitant CABG in an aged patient].
AB  - A 79-year-old man was referred to our hospital complaining of the manifestation
      of mild heart failure. Echo cardiography and LV gram showed sever mitral
      regurgitation by the prolapse of posterior leaflet. CAG revealed coronary artery
      disease affected two vessels (LAD and RCA) without symptoms. Quadrangular
      resection of posterior leaflet (McGoon's method) without annuloplasty and
      concomitant single CABG to the LAD using a saphenous vein were performed.
      Postoperative course was satisfactory and the manifestation of heart failure was
      diminished. Mitral valvuloplasty with concomitant CABG may be a safe and
      effective procedure in the treatment of aged patients.

PMID- 7643506
TI  - [Suture annuloplasty for mitral regurgitation with modified Paneth-Burr's
      method].
AB  - Plication of the leaflets or chordae reconstruction combined with annuloplasty
      cave been the standard procedure of the mitral valve repair for mitral
      regurgitation (MR). We have chosen the JH Kay's method for mitral annuloplasty.
      However, the long term results were not necessarily satisfactory because of
      various types of the mitral lesions. We have adopted the semicircular suture
      annuloplasty (Paneth-Burr's method) as the first choice for MR since May, 1991.
      In this paper, we demonstrate our modified operative procedure of the Paneth
      Burr's method and the operative results. Also, to decide the optimal size of the
      annulus after annuloplasty, we evaluated the changes in size of the annulus and
      extent of mitral regurgitation before and about 16.3 months after surgery in 21
      patients (pts) with MR undergoing Paneth-Burr's method, using Doppler
      echocardiography. On this annuloplasty, a double suture of EPTFE string (GORE
      TEX) guarded with plegets was placed at the margin of the central fibrous body,
      sutured circumferentially around the annulus. Two rows of the suture were crossed
      in every several stitches to prevent cutting. A second suture was placed on the
      opposite side of the annulus in the same fashion. The MR patients were divided,
      by their size of the annulus after annuloplasty, into group A (less than 90% of
      normal annular diameter, 15 pts) and group B (more than 90% of normal annular
      diameter, 6 pts). In 14 of 15 pts of group A, mitral regurgitation was improved
      from grade 2-4 to grade 0-1 postoperatively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7643507
TI  - [Long-term results of mitral valvuloplasty for mitral regurgitation].
AB  - From July 1979 to February 1995, 126 patients, including 4 reoperations, aged
      between 6 months and 77 years underwent mitral valve repair for mitral
      regurgitation. The patients were divided in two groups, 46 patients aged less
      than 16 years in pediatric age group and the other 80 patients in a dult group.
      The methods consisted of asymmetric annuloplasty (Kay-Reed method) in 98 patient,
      Carpentier-Edwards ring annuloplasty in 14, quadrangular resection of the
      posterior leaflet with annuloplasty in 9, and chordal and leaflet repair in 5.
      There was no hospital nor late death in pediatric age group. Three hospital
      deaths and one late death were in adult group. Follow-up was 96% complete and
      totaled 812.1 patient years. Reoperations underwent in 3 pediatric patients and 9
      adults. At 15 years' follow-up, freedom from reoperation was 91.5 +/- 4.7% in
      pediatric age group and 67.1 +/- 12.7% in adults. Freedom from event was 63.5 +/-
      12.1% in adult group. These results suggest that mitral repair with Kay-Reed
      method in pediatric age group is favorable for long-term. In contrast,
      indications for mitral reconstraction with other methods including ring
      annuloplasty should be extended for aged patients with severely dilated annuls
      and degenerated leaflets.

PMID- 7643508
TI  - [Mitral valve reconstruction: for ruptured chordae to the posteromedial
      commissural scallop].
AB  - The advantages of mitral valve repair for pure mitral incompetence are
      established. It is necessary for us to describe suture points more detailed. This
      article presents our standardized maneuver for mitral regurgitation due to
      ruptured chordae to the posteromedial commissural scallop. The first step in the
      repair is placement of a temporary suture in the annulus at attachment of
      posterior commissural chordae and one of posterior cleft chordae. After measuring
      the annular diameter and estimating coaptation, this suture is removed.
      Secondary, rupture of chordae tendinease and adjacent margin of posteromedial
      commissural scallop are resected. Then, one end of a thread is passed through the
      margin at end of this untethered segment of leaflet, and another end is passed
      through the margin of leaflet at opposite end of this segment. Finally, a
      mattress suture using 3-0 Prolene with pledget is placed as a temporary suture.
      Between April 1993 and December 1994, four patients underwent reconstruction of
      mitral regurgitation with ruptured chordae to the posteromedial commissural
      scallop. Left ventriculogram 4 weeks postoperatively showed no regurgitant jet in
      all patients.

PMID- 7643509
TI  - [Mitral valve repair for the treatment of ischemic mitral regurgitation].
AB  - Twenty-six patients with moderate and severe ischemic mitral regurgitation due to
      papillary muscle dysfunction underwent mitral valve replacement (MVR) or mitral
      annuloplasty (MAP) using modified Kay method. Emergent operation was performed in
      12 patients of whom 11 had severe congestive heart failure even under IABP, 5 had
      cardiogenic shock and 9 needed respiratory care with intubation preoperatively.
      Elective operation was performed in 14 patients of whom 6 had history of
      congestive heart failure and 1 had episodes of ventricular tachycardia. As
      intraoperative findings of mitral valve, mural annular dilatation in 84.6%,
      prolapse of anterior leaflet in 23.1%, papillary muscle scar in 15.4%, chordal
      elongation in 15.4% and chordal rupture in 3.8% were seen separately or in
      combination. In 22 patients MAP using modified Kay method and CABG were
      performed, but in 4 patients MVR was needed because of the prominent prolapse of
      the anterior leaflet. Fourteen patients who underwent MAP with CABG and one MVR
      with CABG survived. Hospital mortality was higher in emergent (58.5%) than
      elective operation (28.6%). In the 15 survivors, mitral regurgitation decreased
      below Sellers 2, pulmonary wedge pressure decreased significantly (p < 0.01) and
      NYHA functional class improved to I or II postoperatively. During the follow up
      period of 15-100 (mean 38.7 +/- 21.6) months, 2 MAP+CABG patients died suddenly,
      but the remaining 13 patients were in NYHA class I or II and no progression of MR
      was seen. These results indicated that MAP+CABG is recommendable in the treatment
      of ischemic mitral regurgitation due to papillary muscle dysfunction, in order to
      preserve cardiac function and to reduce valve related complications.

PMID- 7643510
TI  - [Is intraoperative monitoring of transesophageal echocardiography necessary for
      mitral valve repair?].
AB  - To clarify the clinical significance of the intraoperative monitoring for mitral
      valve repair by transesophageal echocardiography (TEE), we evaluated the
      correlation of color Doppler flow area of residual mitral regurgitation (residual
      MR area) between intraoperative and postoperative TEE. Subjects were 12 patients
      (average age was 54.7 years) underwent recently intraoperative TEE. These 12
      patients were divided into two groups: Group A (MR area < 2.0 cm2; n = 8) and
      Group B (MR area > 2.0 cm2; n = 4). None of the 12 patients required second pump
      run. In all cases, residual MR area, as determined using intraoperative TEE, was
      less than 3.2 cm2. One month after surgery, the MR area did not showed an
      increase in Group A, while in Group B it decreased slightly in 2 cases, remained
      unchanged in 1 case and increased slightly in 1. Our findings do not support the
      usefulness of intraoperative monitoring with TEE. It seems difficult to predict
      the outcome of residual MR on the basis of the MR area alone. At present, we
      thought that, possibly, intraoperative monitoring with TEE is indispensable for
      mitral valve repair. A longer follow-up will be necessary to draw firm
      conclusions.

PMID- 7643511
TI  - [Evaluation for mitral valvuloplasty using rasping procedure].
AB  - From April 1992 through July 1994, 7 patients underwent mitral valvuloplasty
      using rasping procedure in conjunction with open mitral commissurotomy. All
      patients had satisfactory postoperative results without the complications such as
      restenosis, regurgitation, infection. However, thromboembolism was observed in 1
      patient at the postoperative 6 months. And no reoperation for repaired mitral
      valve was observed. Transvalvular pressure gradient significantly decreased from
      14.3 +/- 8.5 mmHg to 4.7 +/- 1.6 mmHg after operation. Mitral valve areas
      significantly increased from 1.01 +/- 0.31 cm2 to 1.78 +/- 0.41 cm2 after
      operation. As compared with preoperative value of 0.32 +/- 0.02, postoperative
      left ventricular fractional shortening (LVFS) significantly improved to 0.40 +/-
      0.03. The advantages of this method is considered to be equable and safe
      debridement, and no anticoagulation at late period. Mitral valvuloplasty using
      rasping procedure, except for transmural calcified lesions, is useful and
      effective method. And excellent postoperative long-term results could be
      expected.

PMID- 7643512
TI  - [The long-term result of atrioventricular valvuloplasty and surgical technique].
AB  - The long-term follow-up study was performed on various atrioventricular
      valvuloplasties, and our special technique of annuloplasty was also described. In
      mitral stenosis, 10 and 20 years actuarial survival rates were 82 and 78% in CMC
      and 92 and 83% in OMC with statistically better result. Reoperation free rates at
      10 and 20 years were 86 and 74% in CMC, and 87 and 73% in OMC, although
      statistically better result was shown in OMC at 28 years. In mitral
      regurgitation, 140 patients underwent surgery from 1990 to 1994. MVP was
      successful on 33 patients and the remained 107 patients underwent MVR with St.
      Jude Medical valve. Actuarial survival rates at 5 and 10 years were 94 and 78% in
      MVP, and 92 and 88% in MVR. Complication free rates at these periods were 88 and
      74% in MVP, and 78 and 69% in MVR, showing no statistical difference. In
      tricuspid regurgitation. 166 cases underwent DeVega's annuloplasty with excellent
      result of reoperation free rate of 97% at 10 years.

PMID- 7643514
TI  - 1902: nursing education by correspondence.

PMID- 7643513
TI  - [Extended operation for lung cancer: concomitant resection of the heart or the
      great vessels with the lung].
AB  - We have analysed our experience in 43 patients with lung cancer invading the
      heart or great vessels who underwent surgical resection of the invaded portion of
      the mediastinal organs as well as the primary tumor, and have reviewed the
      literature on the subject of the extended operation for lung cancer invading the
      heart or great vessels. Among our experience of those 43 patients, a single
      mediastinal organ was resected in 32 patients (the left atrium in 20, the main
      pulmonary artery in 7, superior vena cava in 3 and the adventitia of the aorta in
      2), and more than two mediastinal organ were resected in 11 patients (the main
      pulmonary artery and the other in 8, and the left atrium and esophagus or trachea
      in 3). There were 34 squamous cell carcinomas, 4 adenocarcinomas, 3 large cell
      carcinomas and 3 other cell types. Pathology disclosed 6 patients had pT 3 tumor
      (Group 1, 24 patients had pT 4 tumor that had invaded to a single mediastinal
      organ (Group 2) and 11 patients had pT 4 tumor that had invaded to more than two
      mediastinal organs (Group 3). The 5 year survival rate in patients of Group 1, 2
      and 3 were 80%, 32.2% and 0%, respectively. There were statistical differences
      among the survivals of those three groups. We conclude that extended resection
      for lung cancer invading the heart or great vessels is justified if the invasion
      is limited to a single mediastinal organ. Several problems on such extended
      resection were discussed.

PMID- 7643515
TI  - Two nursing careers: 1920's-1940's.

PMID- 7643516
TI  - Nursing--60's style.

PMID- 7643517
TI  - Chronic renal transplant loss.
AB  - Chronic rejection results from recurrent episodes of subclinical or clinically
      evident acute rejection, with or without involvement of chronic rejection
      specific allogeneic immune mechanisms. The tissue damage occurs over a prolonged
      period of time, which allows the emergence of antigen-independent tissue repair
      mechanisms and intrarenal adaptations in response to progressive loss of renal
      mass (Fig. 1). The combination of these mechanisms leads, very likely, to the
      tissue remodeling of chronic rejection. The heterogeneous expression of chronic
      rejection may result from different types and specificities of allogeneic immune
      reactions as well as different contributions of antigen-independent factors that
      modulate the antigen-dependent tissue responses to injury. The extent to which
      these mechanisms participate in the overall picture is presently unknown as
      immunological parameters are not measured routinely in the follow-up of patients
      with chronic graft dysfunction. Furthermore, some grafts may undergo tissue
      remodeling as a consequence of predominantly antigen-independent mechanisms.
      Therefore, the term chronic allograft dysfunction may clinically be preferable
      over chronic rejection to describe the gradual decline in graft function months
      or years after transplantation in the absence of a well-defined mechanism or an
      accepted treatment.

PMID- 7643518
TI  - Extracellular nucleotides as modulators of renal tubular transport.

PMID- 7643519
TI  - Oral administration of L-arginine and captopril in rats prevents chronic renal
      failure by nitric oxide production.
AB  - The effect of oral supplementation of L-arginine, the substrate of nitric oxide,
      (1.25 g/liter water) and captopril (15 mg/liter water) was studied in 5/6
      nephrectomized rats for a period of three months. N-omega-nitro L-arginine, a
      nitric oxide synthase inhibitor, was given orally (70 mg/liter water) with or
      without L-arginine or captopril. The urinary excretion of nitrite (NO2) + nitrate
      (NO3), the known metabolites of nitric oxide, was taken as an index of nitric
      oxide production. Chronic renal failure rats were characterized by a low
      creatinine clearance, high FENa%, proteinuria, hypertension and a low urinary
      excretion of NO2 + NO3; 0.152 +/- 0.06 (P < 0.001) nmol/micrograms creatinine
      compared with 0.481 +/- 0.004 (P < 0.001) in normal rats and 0.479 +/- 0.11 (P <
      0.001) in untreated sham-operated rats. Both L-arginine and captopril were
      effective in the normalization of all these parameters. The combination of L
      arginine and captopril had no additive effects. The nitric oxide synthase
      inhibitor significantly diminished the captopril beneficial effect. It is
      concluded that chronic renal failure in rats is a low nitric oxide production
      state. The supplementation of L-arginine is shown to overcome this condition. It
      is suggested that the beneficial effect of captopril on chronic renal failure is
      through a specific L-arginine--nitric oxide synthase--nitric oxide pathway.

PMID- 7643520
TI  - Isolated rat hepatocyte metabolism is affected by chronic renal failure.
AB  - Metabolic changes due to chronic renal failure (CRF) were studied in isolated
      liver cells. In 14 CRF and 14 sham-operated rats, liver cells were isolated by
      the Berry and Friend method and incubated with various substrates in order to
      study gluconeogenesis, ureagenesis, ketogenesis, oxygen consumption as well as
      cytosolic and mitochondrial adenine nucleotide content. CRF rat hepatocytes
      exhibited a 25% to 45% decrease in gluconeogenesis and ureagenesis (P < 0.05)
      from all the tested substrates (lactate plus pyruvate, fructose, glycerol,
      dihydroxyacetone, alanine and glutamine for gluconeogenesis and alanine,
      glutamine, ammonia and ammonia plus ornithine for ureagenesis), while endogenous
      rates were unaffected. CRF did not alter ketone body production (acetoacetate and
      beta-hydroxybutyrate) from oleate or octanoate. In the presence of either oleate,
      lactate plus pyruvate or ammonia, oxygen uptake as well as cytosolic and
      mitochondrial total adenine nucleotides were unaffected by CRF, while the
      mitochondrial ATP/ADP ratio decreased (P < 0.001). Thus, this study of hepatocyte
      intermediary metabolism during CRF showed an alteration of only gluconeogenesis
      and ureagenesis pathways. Moreover, the association of normal oxygen uptake
      together with decreased mitochondrial ATP/ADP ratio suggest a possible increase
      in hepatocyte ATP demand during uremia.

PMID- 7643521
TI  - Inhibition of proteinase 3 by ANCA and its correlation with disease activity in
      Wegener's granulomatosis.
AB  - Detection of circulating antineutrophil cytoplasmic antibodies (ANCA) to the
      neutrophil serine proteinase, proteinase 3 (PR3), has proven valuable for the
      diagnosis of Wegener's granulomatosis (WG). However, the importance of these
      autoantibodies in the pathogenesis of WG remains unknown. It was recently
      reported that anti-PR3 autoantibodies (PR3-ANCA) from some patients with WG
      inhibit the proteolytic activity of PR3 and interfere with the inactivation of
      PR3 by the physiologic inhibitor, alpha 1-proteinase inhibitor (alpha 1-PI). We
      have studied the effect of PR3-ANCA on the enzymatic activity of PR3 and its
      correlation with disease activity in patients with WG. We purified IgG from 21
      PR3-ANCA positive sera obtained from 17 patients with WG, and determined its
      effect on the esterolytic and proteolytic activity of purified human PR3 using
      Boc-Ala-O-Nitrophenyl ester and fluoresceinated-elastin as enzyme substrates.
      Controls included seven sera containing anti-MPO autoantibodies (MPO-ANCA) from
      patients with systemic vasculitis and seven ANCA-negative sera obtained from
      healthy individuals. We found that PR3-ANCA from 9 of the 17 patients
      significantly inhibited the activity of PR3. There was no correlation between the
      titers of PR3-ANCA and their inhibitory activity. For one extensively
      characterized autoantibody, the inhibition reached 70 to 95% at 20-fold molar
      excess of IgG to enzyme, with an apparent Kiapp of 56.5 microM. This inhibition
      was non-competitive in nature, and was additive to that produced by alpha 1-PI. A
      review of the clinical histories of the patients revealed a strong association
      between active WG and inhibitory autoantibodies.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7643522
TI  - Commercial dialysate inhibits TNF alpha mRNA expression and NF-kappa B DNA
      binding activity in LPS-stimulated macrophages.
AB  - Continuous ambulatory peritoneal dialysis is known to interfere with the normal
      inflammatory responses of macrophages in the peritoneal cavity. Commercial
      peritoneal dialysis solution (CDS) has been shown to inhibit tumor necrosis
      factor alpha (TNF alpha) release from LPS stimulated peritoneal macrophages. To
      further dissect the mechanism of this inhibition, we used human blood-derived
      macrophages or the murine macrophage cell line, P388D1, that were stimulated with
      LPS after pretreatment with CDS, and tested TNF alpha mRNA levels by Northern
      hybridization or reverse transcriptase polymerase chain reaction. Time course
      studies demonstrated that CDS lowered TNF alpha mRNA levels within 15 minutes of
      pretreatment of cells. In addition, the CDS inhibited DNA binding activity of NF
      kappa B that is probably involved in regulation of LPS-mediated transcriptional
      activation of the TNF alpha gene. Inhibition was dependent on both the low pH and
      the lactate in the CDS, but was independent of the osmolarity or glucose
      concentration. The rate of catabolism of TNF alpha mRNA was not affected by CDS
      as demonstrated by actinomycin D chase experiments. Thus, impairment of LPS
      stimulated macrophage function by CDS is associated with low TNF alpha mRNA which
      may be the result of the low activity of NF-kappa B. Since NF-kappa B is involved
      in transcription regulation of a large number of "early activation" genes, CDS
      may interfere with the production of additional immunomodulatory proteins that
      are encoded by genes possessing NF-kappa B site(s) in their promoter region.

PMID- 7643523
TI  - Renal expression of genes that promote interstitial inflammation and fibrosis in
      rats with protein-overload proteinuria.
AB  - Rats with significant proteinuria induced by daily injections of bovine serum
      albumin develop interstitial inflammation and fibrosis. The present study was
      designed to investigate the molecular basis of interstitial monocyte (Mo)
      recruitment and early interstitial fibrosis. Groups of rats were sacrificed after
      one, two and three weeks. Despite an increase in interstitial Mo at week 1, whole
      kidney mRNA levels were not elevated for monocyte chemoattractant protein-1 (MCP
      1), osteopontin or vascular cell adhesion molecule-1 (VCAM-1). Only osteopontin
      mRNA levels were significantly elevated in the renal cortex at four days. At two
      and three weeks, MCP-1 and osteopontin mRNA levels were increased and the
      proteins showed distinct tubular patterns of distribution. By immunostaining
      increased expression of VCAM-1 and intercellular adhesion molecule-1 (ICAM-1) was
      restricted to their presence or the surface of the interstitial inflammatory
      cells. TGF-beta 1 mRNA levels were increased at weeks 1, 2 and 3 (2.1, 2.9,
      3.6x); interstitial and occasional cortical tubular cells expressed TGF-beta 1
      mRNA and protein. There was a progressive rise in the number of cortical
      interstitial fields with increased staining for collagen (col) 1 (18, 29, 44%),
      col III (39, 61, 63%), col IV (7, 13, 29%), laminin (4, 10, 30%), fibronectin
      (14, 28, 37%), tenascin (19, 22, 14%) and in total renal col measured
      biochemically (1.1, 1.4, 2.0x) at weeks 1, 2 and 3, respectively. Renal matrix
      protein mRNA levels were variable and not always predictive of fibrosis. Only col
      I and tenascin levels were increased at week 1; all matrix protein mRNA levels
      except col IV were increased at week 2; but only tenascin, laminin and col IV
      mRNA levels remained elevated at three weeks. Plasminogen activator inhibitor-1
      (PAI-1) and tissue inhibitor of metallo-proteinases (TIMP)-1 mRNA levels were
      significantly increased at two weeks. During the three weeks there was no change
      in urokinase, stromelysin or TIMP-3 mRNA levels. These results suggest that both
      increased matrix protein synthesis and altered matrix remodeling/degradation
      contribute to the final interstitial fibrogenic process in rats with protein
      overload proteinuria. Mo, one of the sources of TGF-beta 1, infiltrate the
      interstitium by complex recruitment mechanisms which may depend in part on
      osteopontin, ICAM-1 and VCAM-1 expression.

PMID- 7643524
TI  - Effects of urodilatin in the rat kidney: comparison with ANF and interaction with
      vasoactive substances.
AB  - We compared the effects of urodilatin (URO) and atrial natriuretic factor (ANF)
      in normal and hydronephrotic kidneys (HNK) of rats. Furthermore, the impact of
      blocking different vasoactive hormones on the action of natriuretic peptides on
      vessels of cortical (C) and juxtamedullary (JM) glomeruli was studied in HNK by
      using URO. In normal kidneys, effects of URO and ANF (1.2, 2.4, 4.8, 12, and
      19.10(-11) mol.kg-1.min-1 i.v.) were not significantly different. At 12.10(-11)
      mol.kg-1.min-1, URO and ANF increased urine flow 5.4 +/- 1.7 and 3.0 +/- 0.8
      fold, increased urinary sodium excretion 20.7 +/- 8.8 and 10.3 +/- 4.0-fold, and
      decreased blood pressure by 13 +/- 2% and 12 +/- 1%, respectively (mean +/- SEM).
      In HNK, URO and ANF (0.4, 0.9, and 2.0.10(-11) mol.kg-1.min-1 i.v. and local
      application of 0.5, 1.0, and 2.0.10(-9) M) dose-dependent dilated preglomerular
      vessels (max approximately 20%), constricted efferent arterioles (max
      approximately 15%), and increased glomerular blood flow of C glomeruli in an
      identical fashion. Comparing URO effects on C and JM arterioles (0.4 and 0.9.10(
      11) mol.kg-1.min-1 i.v.), JM responses were about one third of C responses.
      Angiotensin converting enzyme inhibition (ACEI, 2.10(-6) mol.kg-1 quinapril
      i.v.), combined ACEI and cyclooxygenase inhibition (CYOI, 2.8.10(-5) M
      indomethacin), and endothelin (ET) receptor blockade (10(-6) M BQ 123 and IRL
      1038) diminished preglomerular vasodilation (C and JM) caused by URO infusion.
      Efferent vasoconstriction (C and JM) caused by URO was exaggerated by blockade of
      nitric oxide synthesis (10(-5) M L-NAME) and abolished by combined ACEI and CYOI,
      by bradykinin receptor blockade (4.10(-8) M Hoe 140), and by ET blockade. CYOI
      attenuated only JM efferent constriction. Our results show that URO and ANF
      possess equipotent vascular and similar natriuretic effects in the rat kidney.
      The magnitude of preglomerular vasodilation, which is directly mediated by these
      peptides, depends on the basal level of endogenous vasoconstrictors, while
      efferent vasoconstriction may be mediated by the secondary release of ET.

PMID- 7643525
TI  - Zaprinast accelerates recovery from established acute renal failure in the rat.
AB  - Atrial natriuretic factor (ANF) has been demonstrated to be effective in the
      treatment of acute renal failure (ARF) in both rat and humans. The biological
      effects of ANF are presumed to be mediated by the generation of intracellular
      3',5'-cyclic guanosine monophosphate (cGMP). Therefore, the current investigation
      examined whether zaprinast (M&B 22948), a guanosine 3',5'-cyclic monophosphate
      (cGMP)-specific phosphodiesterase inhibitor, would be effective in the treatment
      of established acute renal failure in the rat. Acute renal failure was induced by
      60 minutes of bilateral renal artery clamping. Twenty-four hours after the
      ischemic insult, rats received either vehicle (5% Dextrose), zaprinast (0.03 or
      0.3 mg/kg/min) or ANF24 (0.2 micrograms/kg/min) intravenously for four hours.
      Renal function, as measured by daily serum creatinine (days 1 to 7) and day 2
      inulin clearances, was dramatically improved by zaprinast but not ANF treatment.
      Forty-eight hours post-renal ischemia, glomerular filtration rate (GFR) was 0.14
      +/- 0.04 (ml/min/100 g body wt) in the vehicle and 0.94 +/- 0.29 in the zaprinast
      treated animals. To evaluate the mechanism by which zaprinast accelerated renal
      recovery, we measured regional blood flow in the postischemic rat kidneys during
      drug treatment with a laser doppler flowmeter. Both high and low dose zaprinast
      significantly increased cortical (17%) and outer medullary blood flow (40% and
      60%), an effect not seen with ANF. In summary, zaprinast is effective in the
      treatment of established ischemic ARF. The mechanism by which zaprinast
      accelerates renal recovery is due to its unique ability to stimulate regional
      renal blood flow and increase intracellular cGMP in the setting of tissue
      ischemia.

PMID- 7643526
TI  - Adenosine stimulation of Na+ transport is mediated by an A1 receptor and a
      [Ca2+]i-dependent mechanism.
AB  - Studies were performed to determine the primary signal transduction mechanism
      that mediates adenosine stimulation of electrogenic sodium transport in renal
      epithelial cells. Experiments were performed on cultured amphibian A6 cells with
      an adenosine analogue that preferentially binds to the A1 receptor,
      cyclohexyladenosine (CHA). Sodium transport was assessed by the equivalent short
      circuit current (Ieq). CHA was found to stimulate Ieq via activation of an A1
      receptor because (1) the threshold concentration was 1 nM compared to that of 10
      microM for the specific A2 agonist CGS21680, (2) CHA inhibited vasopressin (AVP)
      stimulated cAMP production by a pertussis toxin-sensitive mechanism, and (3) the
      action of CHA was inhibited by the A1 antagonist 1,3-dipropyl-8
      cyclopentylxanthine (DPCPX). CHA increased intracellular Ca2+ ([Ca2+]i) and
      stimulated phosphoinositide turnover at concentrations that increased Ieq and in
      a time course that paralleled the increase in Ieq. Ion transport was stimulated
      by a Ca(2+)-dependent mechanism because the CHA induced increase in Ieq was
      inhibited by chelating [Ca2+]i with 5,5'dimethyl BAPTA in a dose-dependent
      manner, with a Ki of approximately 10 microM. The increase in Ieq was also dose
      dependently inhibited by the specific PKC inhibitors dihydroxychlorpromazine and
      chelerythrine, and by trifluoperazine which inhibits PKC and calmodulin. Further
      studies indicated that CHA-stimulated Ieq was independent of cAMP generation
      because CHA did not induce an increase in cAMP accumulation parallel to the
      increase in Ieq in a dose-response analysis, and the adenylate cyclase inhibitor
      2',5' dideoxy-adenosine (DDA) did not affect the CHA-induced increase in
      Ieq.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7643528
TI  - The GATA-3 gene is expressed during human kidney embryogenesis.
AB  - GATA-3 is a transcription factor involved in the differentiation of T lymphocytes
      and additionally expressed in several chicken and mouse embryonic tissues. Using
      in situ hybridization, we found that the human GATA-3 gene is selectively
      expressed in the developing kidney. GATA-3 mRNA is first detected in the Wolffian
      duct from the time of its emergence in the embryonic intermediate mesoderm and
      further expressed in the collecting ducts of the mesonephros until its
      involution. In the metanephros, GATA-3 is expressed in the ureteric bud where it
      is constitutively transcribed, throughout development, along the branching
      process that gives rise to the whole collecting system of the definitive kidney.
      Besides the Wolffian duct and derivatives, we also report the expression of GATA
      3 gene in the glomerular mesangium and adjacent endocapillary cells, in both meso
      and metanephros. This early and specific expression of the GATA-3 gene suggests
      a role for this transcription factor in the differentiation of the human kidney.

PMID- 7643527
TI  - Expression of osteopontin, a urinary inhibitor of stone mineral crystal growth,
      in rat kidney.
AB  - Cultured mouse kidney cortical cells secrete osteopontin, a bone matrix protein
      that is also found in urine. Osteopontin is associated with cell
      proliferation/tumerogenesis and also inhibits kidney stone mineral crystal growth
      [1]. Using antibodies raised against osteopontin isolated from the culture
      medium, we localized osteopontin in normal rat kidney. Fluorescence, confocal and
      electron microscopy revealed osteopontin primarily in cells of the descending
      thin limb of the loop of Henle (DTL) and in papillary surface epithelium (PSE) in
      the area of the calyceal fornix. In situ hybridization with labeled RNA made from
      a cDNA that contains the entire coding sequence for mouse osteopontin revealed
      message at the same sites at which protein was demonstrated by
      immunocytochemistry. Immunogold labeling was localized to a population of dense
      vesicles distinct from lysosomes and endosomes. To examine the turnover of
      osteopontin, rats were injected with the protein synthesis inhibitor
      cyclohexamide, 14 mg/kg, six hours prior to kidney fixation. These kidneys no
      longer demonstrated osteopontin in DTL and the immunofluorescence in the
      papillary surface was attenuated. Thus, osteopontin is secreted at two sites in
      the kidney where urine is highly concentrated in stone mineral constituents. It
      has a relatively rapid turnover, suggesting that it could be subject to
      physiological regulation. Osteopontin may be important in the normal endogenous
      defense against kidney stone formation.

PMID- 7643529
TI  - Active Heymann nephritis in complement component C6 deficient rats.
AB  - The mechanisms of renal injury that result in proteinuria in active Heymann
      nephritis (AHN) remain unclear, though data suggest that in analogy of the
      passive form of the disease the membrane attack complex C5b-9 may be involved.
      AHN was induced in an inbred strain of PVG/c-rats that are totally deficient in
      the C6 component of complement and are unable to form the lytic C5b-9 complex, as
      well as in non-complement deficient PVG/c+ rats that are immunologic identical to
      the deficient strain. In both groups of animals comparably high titers of anti
      Fx1A autoantibodies were found after three weeks and persisted at 40 weeks.
      Proteinuria was also similar in both groups, and was first evident at six weeks.
      High levels of urinary protein, ranging from 200 mg/24 hr to 500 mg/24 hr, were
      found after 10 weeks and persisted up to one year. Renal biopsy findings at
      various times post-immunization were identical in both groups, including
      immunofluorescence staining for Ig and C3 deposits, and also EM findings of
      subepithelial electron-dense deposits were not different. The injection of
      heterologous rabbit complement, that partially and temporarily restored the CH50
      activity in PVG/c- rats did not alter or hasten the disease. Long-term follow-up
      showed that all rats in both groups continued to have severe proteinuria and that
      most animals died between 8 to 12 months after disease induction, without renal
      impairment. EM findings in serial biopsies demonstrated that the growth of the
      subepithelial deposits as measured by surface area occurred between weeks 4 and
      12. A positive correlation (r = 0.94) between the size of the deposits and the
      level of proteinuria was found. These studies demonstrate that the membrane
      attack complex of complement does not play a major role in AHN. The relationship
      of the size of the immune deposits to the level of proteinuria suggests that the
      growth of the immune deposits on itself initiate secondary mechanisms that damage
      the permselective characteristics of the glomerular membrane.

PMID- 7643530
TI  - Modulation of salt transport rate affects DNA synthesis in vivo in rat renal
      tubules.
AB  - In adult male Wistar rats we investigated whether cell proliferation contributes
      to salt load-induced hypertrophy of distal tubules. In one treatment group salt
      transport in the thick ascending limb (TAL) was inhibited by furosemide (7.5
      mg/100 g body wt/24 hr, via osmotic minipump) and stimulated in the successive
      distal segments by simultaneous high salt intake (F + Salt). Controls without
      furosemide treatment had a standard salt intake. All animals received the
      thymidine analog bromodeoxyuridine (BrdU) during 24 and 72 hours, respectively.
      In cryostat sections of the perfusion-fixed kidneys DNA synthesis was assessed by
      immunohistochemistry for BrdU, and for endogenous proliferating cellular nuclear
      antigen (PCNA). Incidence of BrdU- and PCNA-labeled nuclei were quantified in
      proximal tubules, medullary TAL, and cortical distal segments downstream the TAL.
      In control animals low labeling indices were found in all investigated segments.
      After 24 and 72 hours of F + Salt, indices of labeled nuclei were markedly
      increased in distal segments downstream the TAL, whereas they were significantly
      reduced in TAL. In proximal tubules increased DNA synthesis rate was apparent
      only after 72 hours. The data demonstrate that (1.) DNA synthesis rate in nephron
      segments in vivo varies in parallel with changes of their salt transport
      activity; (2.) increased DNA synthesis, thus probably cellular proliferation, is
      a component of the structural response of nephron segments following increased
      salt transport activity.

PMID- 7643531
TI  - Elevated cytosolic calcium of adipocytes in chronic renal failure.
AB  - Chronic renal failure (CRF) is associated with increased calcium content of, and
      impaired lipase release from lipid cells. This has been attributed to a rise in
      the cytosolic calcium ([Ca2+]i) of these cells. However, data on [Ca2+]i of lipid
      cells in CRF and on the mechanisms responsible for such an abnormality are
      lacking. To study this issue we examined the [Ca2+]i and ATP content of lipid
      cells and Vmax of Na(+)-K(+)-ATPase and Ca2+ ATPase of membrane preparation and
      Na(+)-Ca2+ exchange of membrane vesicles of adipocytes from normal rats, 6 week
      CRF, CRF normocalcemic parathyroidectomized (CRF-PTX) and CRF, and normal rats
      treated with verpamil (CRF-V, normal-V). [Ca2+]i in adipocytes of CRF rats was
      higher (199 +/- 8.5 nM) and ATP lower (2.9 +/- 0.31 nmol/10(6) cells) than in
      normal (120 +/- 4.3 nM; 5.7 +/- 0.27 nmol/10(6) cells), CRF-PTX (128 +/- 4.7 nM;
      5.8 +/- 0.39 nmol/10(6) cells), normal-V (121 +/- 3.2 nM; 5.3 +/- 0.36 nmol/10(6)
      cells), CRF-V (123 +/- 7.4 nM; 5.5 +/- 0.30 mmol/10(6) cells). Vmax Ca2+ ATPase
      and the activity of Na(+)-K(+)-ATPase and of Na(+)-Ca2+ exchanger were reduced in
      CRF rats as compared to the other four groups of rats. The values in normal, CRF
      PTX, CRF-V and normal-V rats were not different.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7643532
TI  - Glomerular charge selectivity for anionic and neutral horseradish peroxidase.
AB  - Studies in isolated perfused rat kidney have demonstrated that it exhibits
      apparently normal charge selectivity and tubular uptake of anionic horseradish
      peroxidase (aHRP; pI < 4.0) and neutral horseradish peroxidase (nHRP; pI = 7.5)
      when these proteins are measured for their enzyme activity. The absolute
      fractional clearance values for aHRP and nHRP were 0.006 +/- 0.002 and 0.041 +/-
      0.007, respectively. It is evident, however, that the enzyme assay for
      horseradish peroxidase severely underestimates the quantity of protein in urine
      as compared to measurement of its tritium labeled form through radioactivity.
      Fractional clearances estimated by radioactivity and corrected for tubular
      reabsorption for [3H]aHRP and [3H]nHRP were 0.040 +/- 0.029 and 0.099 +/- 0.043,
      respectively, compared to those estimated by enzyme activity which were 0.012 +/-
      0.004 and 0.070 +/- 0.037, respectively. While charge selectivity between the
      anionic and neutral forms of HRP was still evident, albeit significantly reduced,
      the major feature of this type of analysis is that the clearance of the aHRP
      protein is significantly increased compared to that determined by enzyme assay.
      This difference correlates with the observation that the aHRP protein is markedly
      degraded (61 to 65%), as determined by gel chromatography, during filtration.
      Similar degradation was seen in urine fractions collected after the aHRP protein
      was administered in vivo. Degradation also occurred for the nHRP protein in both
      the perfused kidney and in vivo but to a far lesser extent (approximately 14 to
      21%). These studies demonstrate that the anionic form of HRP was preferentially
      degraded during filtration and that charge selectivity for differently charged
      proteins is not as marked as originally thought.

PMID- 7643533
TI  - Transient inhibition of angiotensinogen production in transgenic mice bearing an
      antisense angiotensinogen gene.
AB  - Angiotensinogen is the precursor of the biologically active hormone angiotensin
      II. Enzyme kinetic parameters suggest that concentrations of plasma
      angiotensinogen are rate limiting in the renin reaction. It is therefore assumed
      that a decrease in angiotensinogen synthesis in vivo would result in a decrease
      in angiotensin II plasma levels and then of blood pressure. To test this
      hypothesis, we generated a transgenic mouse line that carries an inducible
      antisense angiotensinogen gene. Transient inhibition of angiotensinogen synthesis
      could be demonstrated in these transgenic animals. However, the amounts of liver
      angiotensinogen message and plasma angiotensinogen concentrations were rapidly
      back to levels observed in control animals.

PMID- 7643534
TI  - Transport interactions of different organic cations during their excretion by the
      intact rat kidney.
AB  - Organic cations, in addition to being filtrated, are secreted or reabsorbed in
      the proximal renal tubule whereby they have to pass the contraluminal and the
      luminal cell membrane. Interactions with the transport of other organic cations
      can occur at either cell side, leading to inhibition or stimulation of net
      secretion or net reabsorption. A qualitative evaluation of such processes is
      possible by using the in vivo bolus injection of an organic cation as test
      substance. Measuring its urinary excretion profile in relation to that of inulin,
      under control conditions and after application of interfering organic cations, in
      combination with simultaneous registration of its tissue concentration, allows
      the demonstration of interaction and also the tentative identification of the
      cell side at which interference has taken place. As test substance the
      fluorescent organic cation 4-(4-dimethylaminostyryl)-N-methylpyridinium (4-Di-1
      ASP+; denotes permanent positively-charged organic cations was used, having a
      protein binding of 47% under the given experimental conditions. As interfering
      organic cations amiloride, benzylamiloride, choline+, cimetidine, and 2-methyl-4
      (heptafluorobutoxy)-N-methylpyridinium+ were injected. It was found that: (1) 4
      Di-1-ASP+ is filtered and net reabsorbed under control conditions (fractional
      excretion 0.54 +/- 0.1). All net secreted interfering substances, except
      bidirectional transported choline+, injected simultaneously with 4-Di-1-ASP+,
      showed an interference with renal excretion of net reabsorbed 4-Di-1-ASP+, by (2)
      instantaneously increasing its reabsorption, resulting in a 28 to 33% decrease in
      urinary excretion, and (3) augmenting its tissue concentration by 19 to 58%. (4)
      A prolonged effect of the interfering substrates could be observed after a third
      injection of 4-Di-1-ASP+ (without inhibitor) showing an increased tissue
      concentration of 4-Di-1-ASP+ of 36 to 46%. The complex interfering pattern of the
      applied organic cations can be explained by a trans-stimulation of 4-Di-1-ASP+
      net reabsorption at the luminal cell side, leading to an increased intracellular
      content of 4-Di-1-ASP+.

PMID- 7643535
TI  - Regulation of renal Na-HCO3 cotransporter: III. Presence and modulation by
      glucocorticoids in primary cultures of the proximal tubule.
AB  - We looked for the presence of the Na-HCO3 cotransporter in primary cultures of
      the proximal tubule and examined the modulation of this cotransporter by
      glucocorticoid hormones. Primary cultures of the proximal tubule of the rabbit
      have Cl-independent, HCO3-dependent 22Na uptake which is DIDS-sensitive. In
      addition, in cells loaded with BCECF and perfused with Cl-free solution, removal
      of Na was associated with a decrease in intracellular pH which returned to normal
      with re-addition of Na. The pH recovery was not inhibited by EIPA but was
      sensitive to DIDS. These findings are compatible with existence of Na-HCO3
      cotransporter in these cells. We examined the role of glucocorticoids on the
      activity of the Na-HCO3 cotransporter by culturing proximal tubule cells in the
      presence of hydrocortisone and when confluence was reached, hydrocortisone was
      deleted from the medium. In the absence of hydrocortisone, the activity of the
      cotransporter, measured either isotopically or fluorometrically, was
      significantly decreased, whereas re-addition of hydrocortisone 10(-8) M, restored
      the activity of the cotransporter to normal levels. The effect of hydrocortisone
      could not be duplicated by aldosterone, suggesting a glucocorticoid-dependent
      effect. Dexamethasone, a glucocorticoid without mineralocorticoid activity,
      stimulated the activity of the cotransporter within physiologic concentrations
      and this effect was blocked by progesterone. The effect of dexamethasone was time
      dependent and was prevented by cycloheximide, a protein synthesis inhibitor.
      These results demonstrate that primary cultures of the proximal tubule have Na
      HCO3 cotransporter activity which is modulated by physiological concentrations of
      glucocorticoids through a protein synthesis-dependent mechanism.

PMID- 7643536
TI  - Heavy metal mediated inhibition of rBAT-induced amino acid transport.
AB  - rBAT, a protein which is located in the brush border membranes of intestine and
      renal proximal tubule cells, was recently shown to induce electrogenic
      countertransport of neutral and dibasic amino acids after its expression in
      Xenopus oocytes. Here, we studied the effects of heavy metals on rBAT induced
      amino acid transport in Xenopus oocytes to clarify a possible involvement of rBAT
      in heavy metal-induced aminoaciduria. The heavy metals Hg2+ and Pb2+ inhibited
      rBAT-induced amino acid transport with a different profile of action. The Pb2+
      mediated inhibition occurred rapidly upon superfusion and was readily reversible
      upon washout. The maximal inhibition caused by Pb2+ was about 50% of the amino
      acid-induced currents at an apparent affinity (Km) of about 10 microM. In
      contrast, the Hg(2+)-mediated inhibition occurred rather slowly, depending on its
      concentration, and was not reversible during washout with control solution.
      However, the Hg(2+)-mediated amino acid transport inhibition could be reversed
      with Hg2+ chelating agents and reducing compounds. Other oxidative agents, such
      as the membrane permeable 2,2'-Dithio-bis(5-Nitropyridine) (DTNP), but not the
      membrane impermeable 5,5'-Dithio-bis (2-Nitrobenzoic acid) (DTNB), mimicked the
      effect of Hg2+, and their effect could similarly be reversed with 2,3
      Dihydroxybutane-1,4-dithiol (DTE). In conclusion, Pb2+ and Hg2+ inhibit rBAT
      induced amino acid transport in a noncompetitive, allosteric fashion. Blockade of
      rBAT-induced amino acid transport may be involved in aminoaciduria following
      mercury or lead intoxication.

PMID- 7643537
TI  - Metalloproteinase generation by human glomerular epithelial cells.
AB  - In the present study cultured human glomerular epithelial cells (HGEC) were used
      to examine the potential role for these cells in the turnover of the glomerular
      basement membrane (GBM) through the secretion of matrix metalloproteinases. The
      cells were shown by substrate gel electrophoresis to secrete gelatinase activity
      of molecular weights 72 kDa and 92 kDa. The gelatinolytic activity was inhibited
      by EDTA (10 mM), and by both TIMP-I and TIMP-II, but was not inhibited by PMSF
      (2.5 mM), indicating that the enzymes belonged to the metalloproteinase family.
      The identity of the enzymes was confirmed by the use of specific antisera to
      gelatinase A and gelatinase B. In addition, reverse transcription polymerase
      chain reaction (RT PCR) amplification of HGEC mRNA using specific primers to the
      two enzymes yielded single bands of amplified DNA and served to verify the
      identity of the enzymes. In supplementary experiments using both specific
      antiserum and PCR primers it was shown that HGEC express message and secrete both
      the specific metalloproteinase inhibitors TIMP-I and TIMP-II. These results
      indicate that the synthesis and secretion of degradative enzymes and their
      controlling inhibitors by HGEC have the potential to be involved in the turnover
      of the extracellular matrix.

PMID- 7643538
TI  - Is focal segmental glomerulosclerosis really focal? Distribution of lesions in
      adults and children.
AB  - The distribution of lesions of glomerulosclerosis, whether focal or diffuse, has
      important implications for pathogenesis and potential therapeutic response.
      Determination of focal or diffuse nature of lesions from a single section, may,
      however, be misleading. We therefore evaluated the distribution of segmental
      glomerulosclerosis in patients with nephrotic syndrome and idiopathic focal
      segmental glomerulosclerosis (FSGS) by three-dimensional analysis. From our
      files, we identified all such biopsies with a diagnosis established by
      immunofluorescence, electron microscopy, and light microscopy that had > 10
      glomeruli and serum creatine < 3.5 g/dl. Renal biopsies from 15 adults (9 women,
      6 men, age 40.3 +/- 4.2 years and six children (2 girls, 4 boys, age 6.3 +/- 1.4
      years) thus identified had sufficient serial sections for analysis. An average of
      20.0 +/- 2.6 glomeruli in adults versus 25.2 +/- 3.9 in children were examined.
      Sclerosis assessed on a single section involved 31.5 +/- 6.8% of glomeruli in
      adults, contrasting only 11.7 +/- 5.7% in children (P < 0.05). Complete serial
      section analysis was possible in 14.1 +/- 1.6 and 10.7 +/- 1.6 glomeruli in
      adults and children, respectively. After this serial section analysis, the
      percent of glomeruli involved by sclerosis increased to 48.0 +/- 6.6% in adults
      and 23.2 +/- 7.4% in children (P < 0.025). The pattern remained focal in all but
      one case that had the highest serum creatinine. The greater increase in sclerosis
      after serial section analysis in children versus adults reflects the predominance
      of small peripheral, that is, more segmental, lesions in children than
      adults.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7643539
TI  - Interaction of hypertension and diabetes on renal function in black NIDDM
      subjects.
AB  - We studied renal function of 194 black subjects with duration of diagnosed NIDDM
      from 1 month to 36 years to determine the interaction of hypertension and
      diabetes on nephropathy. Renal function was assessed by isotopic GFR and RPF
      studies, and serum creatinine. One hundred seventeen of the 194 subjects had 24
      hour urinary albumin excretion (AER). AER > 300 mg/24 h correlated with longer
      duration of NIDDM, decrease in GFR and RPF, and rise in serum Cr, and all
      subjects were hypertensive. AER 30 to 300 mg/24 h also correlated with a longer
      duration of NIDDM and 80% had hypertension. When 194 subjects were grouped
      according to duration of NIDDM and the presence or absence of hypertension,
      subjects who remained normotensive had normal renal function. In hypertensive
      subjects a decrease in GFR occurred with duration of NIDDM > 1 year and decrease
      in RPF with duration of NIDDM > 5 years. In hypertensive subjects with NIDDM > 10
      years, 36% had impaired renal function (GFR < 80 ml/min/1.73 m2 or serum
      creatinine > 1.4 mg/dl) and 75% had microalbuminuria or clinical proteinuria.
      Within this group, those subjects who developed hypertension after their
      diagnosis of diabetes were likely to have evidence of nephropathy as compared to
      those subjects whose hypertension was diagnosed prior to or simultaneous with
      their diabetes: 17 of 20 (85%) versus 7 of 13 (54%), respectively (P = 0.05).
      These data provide insight into the relationship between hypertension and
      diabetes in the development of nephropathy in black NIDDM individuals.

PMID- 7643540
TI  - Effect of intensive therapy on the development and progression of diabetic
      nephropathy in the Diabetes Control and Complications Trial. The Diabetes Control
      and Complications (DCCT) Research Group.
AB  - The Diabetes Control and Complications Trial (DCCT) has demonstrated that
      intensive diabetes treatment delays the onset and slows the progression of
      retinopathy, nephropathy, and neuropathy in patients with IDDM. A detailed
      description of the effects of this treatment on diabetic nephropathy is presented
      here. In the primary prevention cohort, intensive treatment reduced the mean
      adjusted risk of the cumulative incidence of microalbuminuria (> or = 28
      micrograms/min) by 34% (95% CI 2, 56%; P = 0.04). Furthermore, intensive
      treatment decreased the albumin excretion rate (AER) by 15% after the first year
      of therapy (6.5 vs. 7.7 micrograms/min, P < 0.001). Thereafter the rates of
      change for AER within each treatment group were no different from zero, retaining
      a constant difference in AER between groups in the trial. In the secondary
      intervention cohort with baseline AER < 28 micrograms/min, intensive therapy
      reduced the mean adjusted risk of microalbuminuria (> or = 28 micrograms/min) by
      43% (95% CI 21, 58%; P < 0.0001); the risk of a more advanced level of
      microalbuminuria (> or = 70 micrograms/min) by 56% (95% CI 26, 74%; P = 0.002);
      and the risk of clinical albuminuria (> or = 208 micrograms/min) by 56% (95% CI
      18, 76%; P < 0.01). In the secondary intervention cohort, values for AER at year
      1 were identical at 9 micrograms/min, but the 6.5% change per year in the
      conventional group greatly exceeded the rate of change of -0.3% in the intensive
      group (P < 0.001). Among the 73 secondary cohort subjects with AER levels > or =
      28 micrograms/min but < or = 139 micrograms/min at baseline, the reduction of
      progression to clinical albuminuria with intensive therapy was not statistically
      significant. The longitudinal treatment effect of conventional versus intensive
      therapy (11.0% vs. 2.5% per year, respectively, P = 0.087) was similar in
      magnitude to that among patients with AER < 28 micrograms/min at baseline. For
      the primary, secondary and combined cohorts, there were no significant
      differences in the rates of change in creatinine clearance (CCr) between
      treatment groups during the study. Only seven subjects in the entire study (2
      intensive, 5 conventional) developed urinary AER > or = 208 micrograms/min
      coupled with a CCr < 70 ml/min/1.73 m2. Neither the rate of change of blood
      pressure nor the appearance of hypertension (BP > 140/90 mm Hg) differed
      significantly between treatment groups in the primary, secondary or combined
      cohorts.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7643541
TI  - Eleven years of chronic hemodialysis in Uruguay: mortality time course.
AB  - Uruguay is a developing country with 3.1 million inhabitants. Chronic dialysis
      treatment (CDT) began to spread after the creation of the National Fund of
      Resources (NFR) in 1980. This fund receives contribution from all inhabitants to
      finance, among others, the high cost treatment, dialysis and renal
      transplantation (RT). We analyzed the data base from 1981 to 1991 of the
      Hemodialysis National Registry to find the mortality time course. To compare with
      other populations, indirect standardization methods were used. Two thousand and
      seventy-one patients received chronic hemodialysis treatment (CHT) during the
      period cited. Incidence and prevalence of end-stage renal disease (ESRD)
      increased from 32 to 90 and from 38 to 390 patients per million population,
      respectively. Annual gross mortality decreased from 21 to 9% in spite of a
      simultaneous increase in the percentage of high risk patients. According to the
      age-matched national general mortality, the ratio between observed and expected
      deaths was 21 in 1981 and 4 in 1991. The standardized death rate was 142.8
      deaths/1000 patient-years at risk when the USA ESRD 1987 to 1989 mortality rate
      by age, race and diagnosis was used as a standard. These results point out that
      it is possible to provide ESRD treatment in developing countries to achieve
      appropriate comparative results in delaying mortality.

PMID- 7643542
TI  - Increased glomerular filtration rate after withdrawal of long-term
      antihypertensive treatment in diabetic nephropathy.
AB  - Initiation of antihypertensive treatment (AHT) in hypertensive insulin-dependent
      diabetic (IDDM) patients with diabetic nephropathy (DN) induces a faster initial
      (0 to 6 months) and a slower subsequent (6 months to end of observation) decline
      in GFR [delta GFR (ml/min/month) approximately 1.5 vs. 0.35]. Whether this
      initial phenomenon is reversible (hemodynamic) or irreversible (structural
      damage) after prolonged AHT is not known. To elucidate these mechanisms we
      investigated 42 hypertensive IDDM patients (16F/26M, age 40 +/- 7 years, mean +/-
      SD) with DN receiving AHT (angiotensin converting enzyme inhibition, N = 30) for
      6 (2 to 15) years [median (range)]. GFR (ml/min/1.73 m2), arterial blood pressure
      (BP, mm Hg) and albuminuria (mg/24 hr) were measured the last day on AHT and one
      month after withdrawal of AHT. The measured variables were all significantly
      elevated after withdrawal of AHT: GFR [mean(SEM)] from 76(4) to 81(4) (P <
      0.0001), BP [mean(SEM)] from 140/82 (2/1) to 151/89 (2/1) (P < 0.0005) and
      albuminuria [geometric mean (antilog SEM)] from 704 (1.2) to 1122 (1.2) (P <
      0.0001). A correlation between relative rise in systolic blood pressure (delta
      Sys%) and relative change in GFR (delta GFR%) was found (r = 0.44, P < 0.005).
      Our results render some support of the hypothesis that the faster initial decline
      in GFR is due to a functional (hemodynamic) effect of AHT, which does not
      attenuate over time, while the subsequent slower decline reflects the beneficial
      effect on progression of diabetic nephropathy.

PMID- 7643543
TI  - Decreased clearance of low-density lipoprotein in uremic patients under dialysis
      treatment.
AB  - The clearance of low-density lipoprotein (LDL) was studied in eleven patients on
      hemodialysis (HD) treatment and nine patients on continuous ambulatory peritoneal
      dialysis (CAPD) treatment and compared with the clearance of LDL in nine control
      subjects. The clearance rates for LDL (fractional catabolic rate, FCR) in all the
      uremic patients (FCR for LDL 0.305 +/- 0.075 pools/day, mean +/- SD) were
      significantly lower than the clearance of LDL in the control subjects (FCR for
      LDL 0.376 +/- 0.045 pools/day; P = 0.01). The clearance of LDL in the HD patients
      (FCR for LDL 0.334 +/- 0.066 pools/day) was only mildly decreased in comparison
      to the control subjects (P = 0.122), but the clearance of LDL in the CAPD
      patients was markedly decreased (FCR for LDL 0.268 +/- 0.072 pools/day) in
      comparison to the control subjects (P = 0.001). The FCR for LDL among all the
      patients was negatively related to the plasma total cholesterol (r = -0.56, P =
      0.01) and LDL cholesterol concentration (r = -0.76, P = 0.0002) and LDL
      apolipoprotein B concentration (r = -0.48, P = 0.03). In conclusion, the
      clearance of LDL is decreased in uremic patients on dialysis treatment. This
      alteration in the LDL metabolism of the uremic patients may contribute to their
      accelerated atherosclerosis.

PMID- 7643545
TI  - Development of secondary hyperparathyroidism and bone disease in diabetic rats
      with renal failure.
AB  - Renal osteodystrophy in diabetic patients on maintenance hemodialysis is
      characterized by a higher prevalence of low bone turnover and is associated with
      a relative deficiency of parathyroid hormone (PTH) as compared with non-diabetic
      hemodialysis patients. The goal of the study was to evaluate how diabetes
      affected the development of secondary hyperparathyroidism (2 degrees HPT) and
      bone disease in azotemic rats. Three groups of 5/6 nephrectomized, pair-fed male
      Wistar rats maintained on a high phosphorus (1.2%) diet were studied: (1) the
      control group, non-diabetic azotemic rats (NDR); and two streptozotocin-induced
      diabetic azotemic groups, (2) poorly-controlled diabetic rats (PCDR) which
      received only enough NPH insulin to maintain the blood glucose between 300 and
      400 mg/dl, and (3) well-controlled insulin-treated diabetic rats (IDR) which
      received a continuous insulin infusion for 14 days via a subcutaneously implanted
      miniosmotic pump. Serum calcium, phosphorus and creatinine levels were similar
      among the three groups. Blood glucose levels were greater in the PCDR group than
      the IDR and NDR groups (358 +/- 11 vs. 83 +/- 9 and 87 +/- 8 mg/dl, respectively;
      P < 0.001). Rats in the PCDR group weighed less at sacrifice as compared with the
      IDR and NDR groups (P < 0.05). Serum PTH levels (normal 47 +/- 2 pg/ml) were
      elevated, but not different among the three groups (136 +/- 34, 147 +/- 21 and 98
      +/- 8 pg/ml in the PDCR, IDR and NDR groups, respectively).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7643544
TI  - Verapamil reverses abnormal [Ca2+]i and carbohydrate metabolism of PMNL of
      dialysis patients.
AB  - The basal levels of cytosolic calcium ([Ca2+]i) of polymorphonuclear leukocytes
      (PMNL) are elevated in hemodialysis (HD) patients, and this abnormality has been
      implicated in the dysfunction of the PMNL of these patients. The elevated [Ca2+]i
      appears to be due to PTH-induced entry of calcium into PMNL, an action that may
      be prevented by calcium channel blockers. We examined [Ca2+]i and carbohydrate
      metabolism of PMNL of normal subjects and of HD patients before, after eight to
      nine weeks of verapamil therapy (120 mg/day), and after eight to ten weeks of
      discontinuation of verapamil treatment. In HD patients, the basal levels of
      [Ca2+]i of PMNL are elevated and their glucose uptake, the activity of total and
      active forms of glycogen synthetase, and glycogen content are reduced compared to
      values in normal subjects (P < 0.01). These derangements were normalized after
      verapamil therapy and re-emerged after discontinuation of treatment with
      verapamil despite no change in blood levels of PTH. The results indicate that the
      elevation in [Ca2+]i of PMNL and the consequent derangements in carbohydrate
      metabolism of these cells are treatable with a calcium channel blocker. The data
      assign a valuable role for calcium channel blockers for the amelioration of some
      aspects of cell dysfunction of uremia.

PMID- 7643546
TI  - Induction of heat-shock proteins does not prevent renal tubular injury following
      ischemia.
AB  - The possible protective effect of heat-shock proteins (HSPs) on ischemic injury
      to renal cells was assessed in two different experimental models: ischemia-reflow
      in intact rats and medullary hypoxic injury as seen in the isolated perfused rat
      kidney. Heat shock was induced by raising the core temperature of rats to 42
      degrees C for 15 minutes. Following this, Northern blots showed enhanced gene
      expression of HSP70, HSP60 and ubiquitin at one hour and reaching a maximum by
      six hours after heat shock in all regions of the kidney, but most prominently in
      medulla and papilla. The HSP70 protein in the kidney, estimated by
      immunohistochemical means, was detectable 24 hours following heat shock and
      further increased at 48 hours following heat shock. In the first set of
      experiments, the animals underwent uninephrectomy followed by cross clamping of
      the remaining renal artery for 40 minutes prior to reflow. Serum creatinine and
      urea nitrogen rose to 3.15 +/- 0.98 and 126.4 +/- 62.5 mg/dl at 24 hours. No
      significant differences were observed at 24, 48 and 72 hours after reflow between
      these values in control rats and rats pretreated with heat shock 48 hours
      earlier. Severe morphological damage to proximal tubules of the renal cortex was
      observed to the same extent in both groups. In a second set of experiments, the
      right kidney was removed either 24 or 48 hours after heat shock and perfused in
      isolation for 90 minutes. Functional and morphological parameters were compared
      with those of isolated perfused kidneys obtained from animals that had not been
      subjected to heat shock.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7643547
TI  - Effect of diabetes and peritonitis on the peritoneal equilibration test.
AB  - Peritoneal equilibration tests (PET) were performed on 47 patients (15 diabetics)
      who had been on CAPD for 1 to 112 months. Among new patients on CAPD (1 to 3
      months) with no history of peritonitis, diabetics had higher D/PCr than non
      diabetics (P < 0.02). However, after > or = 7 months of CAPD, in patients with <
      or = 2 episodes of peritonitis, glucose and creatinine transport rates were lower
      (P < 0.05) in diabetic than non-diabetic patients. Among patients on CAPD for >
      or = 7 months, creatinine (P < 0.05) and glucose transport (P < 0.01) were higher
      in patients with a history of > or = 3 episodes of peritonitis than in those with
      < or = 2 episodes. Drain volumes did not differ between any of the subgroups (all
      P > 0.05). The observations in patients newly established on CAPD were
      substantiated in a larger study of 55 non-diabetic and 35 non-insulin dependent
      diabetic patients. D/D0 glucose correlated with plasma glucose (r = 0.40, P <
      0.02) in the diabetic group. Net ultrafiltration was reduced in hyperglycemic (P
      = 0.022) but not normoglycemic diabetics (non-diabetics 231 +/- 167 ml,
      hyperglycemic diabetics 127 +/- 177 ml, normoglycemic diabetics 238 +/- 159 ml).
      Creatinine clearance was higher in normoglycemic (P = 0.02) but not hyperglycemic
      diabetics (non-diabetics 6.8 +/- 0.9 ml/min, hyperglycemic diabetics 6.9 +/- 0.8
      ml/min, normoglycemic diabetics 7.4 +/- 0.7 ml/min). These data show that
      diabetes and peritonitis incidence should be borne in mind when interpreting
      results of the PET.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7643548
TI  - In vitro formation of advanced glycation end products in peritoneal dialysis
      fluid.
AB  - Glycation of proteins in the peritoneum might occur due to the extremely high
      glucose concentrations (75 to 214 mmol/liter) in the dialysate of patients on
      continuous ambulatory peritoneal dialysis (CAPD) and may be involved in the
      etiology of ultrafiltration failure. Formation of both early (glycated albumin)
      and late (advanced glycation end products; AGE, measured as protein-derived
      fluorescence intensity, FI) Maillard reaction products was studied in vitro in
      dialysis fluids obtained from seven patients on CAPD and in phosphate buffered
      saline (PBS) controls paired for glucose and albumin concentrations. Percentage
      glycated albumin (median, range) increased (P < 0.02) from baseline after 10 and
      21 days in both dialysate and PBS but did not differ (P > 0.05) between the two
      media at any time point (day 0, 3.6, 3.1-4.5 vs. 4.1, 3.0-4.6; day 10, 19.4, 7.9
      54.8 vs. 19.1, 8.7-50.1; day 21, 29.0, 12.0-75.6 vs. 30.0, 11.7-69.8). Glycated
      albumin formation was linearly related to the glucose concentration (r > 0.98, P
      < 0.001) in both dialysate and PBS at 10 and 21 days. FI (U/g/liter albumin,
      median, range) increased (P < 0.02) from baseline after 10 and 21 days in
      dialysate but only after 21 days in PBS; this increase was significantly greater
      (P < 0.02) in dialysate than in PBS after 10 and 21 days (day 0, 41, 36-46 vs.
      42, 37-46; day 10, 99, 88-161 vs. 51, 34-68; day 21, 113, 102-239 vs. 68, 54-91).
      After 21 days, FI was significantly related to glucose concentration (r = 0.90, P
      < 0.01) and to % glycated albumin (r = 0.92, P < 0.01) in PBS but not in
      dialysate (P > 0.05). AGE formation, but not glycation, decreased as a function
      of the dialysate dwell time and was inhibited by aminoguanidine. Our results
      demonstrate that formation of AGE products occurs in dialysis fluid and that
      factors in dialysate can modulate this process.

PMID- 7643549
TI  - Dermal angiopathy in hemodialysis patients: the effect of time.
AB  - We studied skin biopsies from 14 patients after 6 months to 18 years on
      hemodialysis (HD) to discern any effect of duration of treatment on skin and
      dermal capillaries. Patients selected for biopsy were without evidence of other
      diseases known to affect vasculature such as diabetes mellitus. Pathological
      changes compared with duration of HD were: capillary wall thickening, endothelial
      proliferation and new capillary formation, lipid content, and epidermal atrophy.
      Severity of morphologic changes were graded from 0 to 4+ by a pathologist who had
      no knowledge of HD duration. The earliest change observed was reduplication of
      the capillary basement membrane. Narrowing of capillary lumina due to endothelial
      cell proliferation and new capillary formation were noted after five years of HD;
      lipid droplets were noted in capillaries by five years; and epidermal atrophy by
      10 years. Progressive severity of each finding was associated with length of time
      on HD. Neither amyloid nor Ca++ deposits were observed in any specimens. By
      clinical observation, easy bruisability and increased skin fragility were worse
      the longer the patient was on HD. Capillary occlusion inducing tissue ischemia
      could be a cause of the atrophic skin changes noted. However, no patient
      manifested dermal necrosis. While pathogenesis of the capillary changes in uremic
      skin is unknown, the changes have been shown to stabilize following successful
      kidney transplantation.

PMID- 7643550
TI  - Osteoblastic intracellular pH and calcium in metabolic and respiratory acidosis.
AB  - In vitro metabolic acidosis (Met) induces greater bone mineral resorption than
      respiratory acidosis (Resp). Met, but not Resp, inhibits osteoblasts which
      control many aspects of osteoclastic function. To determine whether at a similar
      decrement in extracellular pH, Met and Resp would induce different changes in
      intracellular pH (pHi) and/or intracellular calcium concentration ([Ca2+]i) of
      osteoblasts, we measured pHi and [Ca2+]i in an osteoblast-like rat osteosarcoma
      cell line (UMR-106). Cells were grown to confluence on glass slides and loaded
      with either 1.5 microM BCECF, for pHi, or 1.5 microM Fura-2, for [Ca2+]i, in
      control (Ctl; pH approximately 7.40, PCo2 approximately 40, [HCO3-] approximately
      24) medium. The fluorescence ratio at excitation wavelengths of 502 and 440 nm
      was measured for pHi and at 340 and 380 nm for [Ca2+]i. Following a baseline scan
      in Ctl medium, cells were transferred to either Met (pH approximately 7.10, PCo2
      approximately 40, [HCO3-] approximately 12), Resp (pH approximately 7.10, PCo2
      approximately 80, [HCO3-] approximately 24) or Ctl conditions. Medium pH, PCo2
      and [HCO3-] were held constant over the course of the experiment. Compared to
      Ctl, pHi was lower in Met (P < 0.001) and even lower in Resp (P < 0.001 vs. Met
      and vs. Ctl). These changes were maintained over the period of observation.
      Compared to Ctl, [Ca2+]i was higher in Met (P < 0.001) and even higher in Resp (P
      < 0.001 vs. Met and vs. Ctl) within 20 to 100 seconds. However, after 100 seconds
      [Ca2+]i was not different in the three groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7643552
TI  - Kidney and urinary tract disease in ancient Babylonia, with translations of the
      cuneiform sources.
AB  - The large corpus of Babylonian medical texts is much less known to medical
      history than the contemporary medical papyri from Egypt, but offer a rich new
      source of information regarding ancient diagnosis and treatment of disease. The
      Babylonian physicians systematically noted systems related to kidney and urinary
      tract diseases. Pharmacological prescriptions tended to consist of plant and
      mineral substances administered either orally in drinks, or were inserted
      directly into the urethra through a tube.

PMID- 7643551
TI  - Parathyroidectomy does not prevent the renal PTH/PTHrP receptor down-regulation
      in uremic rats.
AB  - In a recent study we demonstrated that the PTH/PTHrP receptor (PTH-R) mRNA was
      markedly down-regulated in the remnant kidney of uremic rats with severe
      secondary hyperparathyroidism. Among the factors potentially implicated in this
      down-regulation, to date only PTH has been demonstrated to modulate PTH-R
      expression. Here, we examined the effect of thyroparathyroidectomy (TPTX) on the
      renal expression of PTH-R in rats with normal renal function or with chronic
      renal failure (CRF) induced by 5/6 nephrectomy. Four groups of rats were studied:
      control, TPTX, CRF, and CRF + TPTX. Moderate-degree renal failure was documented
      by mean (+/- SD) creatinine clearances (microliter/min/100 g body wt) of 259 +/-
      40 and 212 +/- 45 in CRF and CRF + TPTX rats, compared with 646 +/- 123 and 511
      +/- 156 in control and TPTX rats, respectively. Plasma phosphorus, calcitriol,
      and ionized calcium were significantly lower in CRF and CRF + TPTX than in
      control animals. Plasma ionized calcium and calcitriol were also lower in TPTX
      than in control rats. Plasma PTH levels (pg/ml) were increased in CRF rats (41.8
      +/- 29.4), and markedly decreased in TPTX (10.1 +/- 7.8) and CRF + TPTX (8.0 +/-
      3.8) rats compared with control rats (21.7 +/- 7.5). Northern blot analysis
      showed that the level of the steady-state PTH-R mRNA in the kidney of CRF and CRF
      + TPTX rats was markedly decreased compared with that of control rats, the ratios
      of PTH-R mRNA/beta-actin mRNA being 0.28 +/- 0.04 and 0.27 +/- 0.03 versus 0.54
      +/- 0.05, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7643553
TI  - The contribution of acidosis to renal osteodystrophy.

PMID- 7643554
TI  - [The role of complex diagnostic examination in von Hippel-Lindau disease].
AB  - Von Hippel-Lindau disease belongs to phakomatosis. It is a dominantly autosomally
      inherited disease. The aim of the study was to present and evaluate different
      methods of diagnostic examinations (computer tomography, magnetic resonance
      imaging and ultrasonography) in 14 patients with the disease. The results of
      investigations showed a wide variety of visceral manifestations. All the patients
      are carefully followed up. Control examinations every six months allow to check
      for and treat any new pathological changes in the retina.

PMID- 7643555
TI  - [The state of the eye in children with Down syndrome caused by trisomy 21
      translocation].
AB  - This paper presents results ophthalmological examination of 16 children with
      translocation trisomy 21/21 and 14/21 selected among group 192 patients with Down
      syndrome confirmed by cytogenetic examination. Ophthalmological state in the
      children with chromosomal aberration and simple trisomy 21 was similar.

PMID- 7643556
TI  - [Effect of prostaglandin inhibitors on leukocyte infiltration and on leukocytes
      in tears after experimental injury of the corneal epithelium].
AB  - The effect of drug inhibiting prostaglandin biosynthesis on permeation of
      leucocytes to tears and cornea after experimental removal of the epithelium was
      observed. It was shown that 1% indomethacin solution and 0.5% ibuprofen solution
      considerably decreased the number of leucocytes in tears and their infiltration
      to the proper substance and negatively affected regeneration of corneal
      epithelium. The investigations have shown that prostaglandin inhibitors inhibit
      leucocyte infiltration and may, in effect, decrease the number of proteolytic
      enzymes that are secreted by these cells.

PMID- 7643557
TI  - [Quantitative assessment of blood-aqueous humor barrier permeability using
      densitometry methods combined with high performance thin layer chromatography].
AB  - The paper presents an original method of examining blood-aqueous humor
      permeability. The examinations were performed on grey rabbits that had been
      intravenously injected 10% fluorescein solution. Subsequently, at definite time
      intervals from the moment of the administration, fluid of the anterior chamber
      was taken in which the amount of aqueous fluorescein permeating to aqueous humor
      was measured. The measurements were performed using the method of high potency
      thin layer chromatography (HPTLC) in DS type chambers. Examination results were
      presented as densitometry, and the area of individual points was counted using a
      computer programme. This method yielded a diagram quantitatively presenting
      fluorescein permeation from the blood to the aqueous humor.

PMID- 7643558
TI  - [Proteolytic activity of the vitreous body].
AB  - It was found that the human and bovine vitreous contains a proteolytic enzyme(s)
      which demonstrates characteristic features of cathepsin D. It acts in acidic pH
      with various activity, dependent on the condition of the eye and actively digests
      native and denatured protein substrates. It demonstrates a high susceptibility to
      the inhibitory action of pepstatin. The role of this enzyme in physiology and
      pathology of the eye is discussed.

PMID- 7643559
TI  - [Evaluation of changes in cells of conjunctival epithelium in dry eye syndrome by
      impression cytology].
AB  - 48 eyes of 24 patients with dry eye syndrome and 22 eyes of 11 normal subjects
      (control group) were examined with the technique of impression cytology. The aim
      of this paper was to describe changes in the cells conjunctival epithelium in dry
      eyes and to evaluate relationships between cytological alternations and the
      clinical severity of the disease. For clinical evaluation we performed medical
      history, slit lamp examination, rose bengal staining, break-up time, Shirmer I
      test. In the specimens from dry eyes we observed morphological changes of the
      epithelial cells, different nuclear alterations, decrease of the goblet cells
      density. The degree of cytological changes was related to severity of dry eye
      syndrome. The impression cytology is a noninvasive, simple method, providing
      valuable information for diagnosis and therapeutic control of dry eye disorders.

PMID- 7643560
TI  - [Polyamine system in experimental retinopathy of prematurity].
AB  - Spermidine (SPD) and spermine (SP) concentrations and the activities of ODC and
      SAT have been measured in retina and lens of the rats maintained in 60%
      atmospheric oxygen for the first 14 days life. Hyperoxia, known to cause
      retardation of vessel growth, was associated with some reduction of the enzyme
      activities and polyamine levels.

PMID- 7643561
TI  - [Creatine kinase in strabismus surgery].
AB  - The paper presents results concerning serum creatine kinase (CPK) activity before
      and at different times following the surgery of extraocular muscles at
      concomitant strabismus. The operation evokes statistically significant increase
      of CPK activity which tends to normalize during healing processes.

PMID- 7643562
TI  - [Eyeball axis changes in children's myopia].
AB  - The aim of study was to assess changes in eyeball axial length in myopic children
      depending on age in comparison with hyperopic and emmetropic groups. The study
      group consisted of 200 children (100 girls and 100 boys), from 3 to 17 years old
      (mean 9.8). Myopia was diagnosed in 376 eyes (-4.0 D to -24.0 D, mean -9.64 D)
      with axial length from 21.0 to 30.95 mm (mean 26.05 mm). Control group consisted
      of 334 eyes (167 children) with mean refraction +0.53 D and axial length from
      20.0 to 23.9 mm (mean 22.36 mm). We have used the Statgraphics program for
      statistical analysis. A statistically significant difference was found between
      mean eyeball axial length within myopic group of girls (mean 25.77 mm) and boys
      (mean 26.31 mm) with p = 0.321 and significance level alpha = 0.05. The axial
      length increases irregularly over time. The axis of the eyeball in myopic
      children aged between 3 and 17 increases more than in emmetropic and hyperopic
      (up to 1.0 D) children.

PMID- 7643563
TI  - [Diagnostic B-scan ultrasound of the lens before cataract surgery with
      intraocular artificial lens implantation].
AB  - The aim of this paper is to elaborate an ultrasound method for the examination of
      anterior segment of the eye with use of standard B-scan 10 MHz ultrasonography.
      Usefulness of this method was estimated in crystalline lens pathology. Own
      designed "upside down funnel" made of plastic enabled immersion eye examination
      38 eyes with senile cataract and traumatic cataract were diagnosed. It was proved
      that the described method makes possible to estimate different lens pathology. It
      is especially recommended to examine posterior lens capsule and to avoid possible
      complication during surgery. The method makes it possible to undertake optimal
      decision before surgery.

PMID- 7643565
TI  - [Retinitis pigmentosa in Kearns-Sayre syndrome resulting from mutation of
      mitochondrial DNA "de novo"].
AB  - We present a case of Kearns-Sayre syndrome diagnosed in a boy with retinitis
      pigmentosa ophthalmoplegia, ancephalomyopathy and cardiomyopathy. A single large
      scale mtDNA deletion at very low level in the blood sample using Southern blot
      analyses and multiprimer DNA amplification was detected. This case demonstrates
      that retinitis pigmentosa may be due to genetic mitochondrial disturbances.

PMID- 7643566
TI  - [Optic neuritis in children and adolescents].
AB  - The aim of the study was to analyse the cause, course and results of treatment in
      cases of optic nerve inflammation, including frequency of recurrencies. One
      hundred and ten children aged 2-18 years treated in our clinic from 1989 to 1994
      were examined. Mean age was 13 years. Bilateral inflammation was found in 60% of
      cases, 176 eyes were assessed. The disease was more frequent in autumn, winter.
      In children below 14 (62%) inflammation concerned the intraocular part of the
      nerve while in older children it was mainly retrobulbar. Recurrence of the
      disease was observed in 1/3 of cases. In younger patients, the cause of the
      inflammation was usually viral infectious disease or chronic focal infection. In
      older children, the main causes were trauma or underlying neurological diseases.
      The treatment administered resulted in a normalisation of the visual field in
      more than half of the cases and visual acuity improvement in 73.5% of cases after
      retrobulbar inflammation, and in 75% of cases after intra-bulbar inflammation.
      During an average follow-up of 3 years, full visual acuity was achieved in 56% of
      eyes after retrobulbar inflammation and 46% of eyes after intra-bulbar
      inflammation. Signs of post-inflammatory neuropathy were present in 46% of eyes.
      Full recovery of visual function was achieved especially in those cases where it
      was not deeply decreased during the disease.

PMID- 7643564
TI  - [Comparison of clinical and ultrasonographic results in eyes with silicone oil].
AB  - 20 eyes filled with silicone oil were examined clinically and with
      ultrasonography. Both examinations were performed by two independent groups of
      investigators. The results were compared according to the extent of retinal
      detachment and its features. The authors discussed the reasons of differences
      between the two methods. The common difficulties to interpret USG pictures of
      silicon oil filled eyes are discussed.

PMID- 7643567
TI  - [To picture something].

PMID- 7643569
TI  - [Quality control of closed systems for endobronchial suction].

PMID- 7643568
TI  - [Mobilization].

PMID- 7643570
TI  - [Lyme borelliosis--diagnosis and therapy from a neurological viewpoint].

PMID- 7643571
TI  - [Eye diseases in newborns and infants. 2].

PMID- 7643572
TI  - [From the hospital to the nursing home].

PMID- 7643574
TI  - [Quality of care and cost containment can be combined].

PMID- 7643573
TI  - [The force that causes all movement].

PMID- 7643575
TI  - Molecular cellular mechanisms of training effects.
AB  - The review paper was composed in order to (1) discuss the mechanism responsible
      for the actualization of the adaptive protein synthesis in training, and (2)
      indicate the necessity for further studies in this field. Genome activation is
      common for systematic exercising. Depending on the specific nature, exercises
      result in the formation of metabolic and hormonal inductors acting on the
      cellular genetic apparatus. The final results of the adaptive protein synthesis
      are determined by the combination of influences exerted by transcription,
      translation and post-translation control.

PMID- 7643576
TI  - Changes of physical performance as indicators of the response to enhanced
      physical education.
AB  - The value of field performance tests in the assessment of a programme of enhanced
      physical education has been examined in a 3-factor study of students over all 6
      primary school grades. The enhanced programme under review offered a one hour of
      required physical education daily from age 7 to 12 years, taught by a specialist
      physical educator. Control students from immediately preceding and succeeding
      classes continued with the standard programme, a standard single period of
      physical education per week taught by a nonspecialist. Subjects were classed by
      gender, environment (urban vs rural school) and the experimental intervention to
      allow analysis by MANOVA. Students in the experimental programme showed small but
      statistically significant gains in laboratory measures of aerobic power and
      muscle strength relative to controls. In general, these responses were mirrored
      by gains in scores on the Canadian Association for Health Physical Education and
      Recreation (CAHPER) field performance test battery. The latter tests also
      suggested gains of anaerobic power, coordination and muscular endurance. It is
      concluded that an enhanced programme of physical education can enhance function
      in primary school students, but the size of gains is not a strong argument for
      such programmes. Further, gains in performance test scores indicate the
      direction, but not necessarily the magnitude of programme responses.

PMID- 7643577
TI  - Fitness level and postexercise energy expenditure.
AB  - This study was designed to investigate the effect of fitness level on excess
      postexercise oxygen consumption (EPOC) in five endurance trained and five
      sedentary male volunteers. The possible influence of differences in body weight
      and exercise energy expenditure were controlled by employing a weight-supported
      (cycle ergometer), 300 kilocalorie exercise. Exercise intensity was equal to 50%
      of each subject's previously determined peak oxygen uptake (VO2). VO2 was
      measured for 1 hr prior to exercise to establish the baseline value, and
      continuously in the postexercise period until the baseline value was achieved.
      Duration of EPOC was 16.6 +/- 3.1 minutes and 20.4 +/- 7.8 minutes in the fit and
      unfit groups, respectively (p > 0.05). Magnitude of EPOC, which was not
      significantly different between the groups, averaged 12.2 +/- 3.1 kcal in the fit
      and 12.2 +/- 4.3 kcal in the unfit group. The results suggest that EPOC following
      a weight-supported exercise of an intensity and duration frequently used by
      individuals who begin an exercise program for weight control is not compromised
      by differences in body weight or fitness level.

PMID- 7643578
TI  - Effects of consecutive exercise days of jogging or cycling on the resting
      metabolic rate and nitrogen balance.
AB  - The resting metabolic rate (RMR) following recovery from level jogging, which
      includes an eccentric component, was hypothesized to be greater and remain
      elevated longer than following concentric cycling due to repair of exercise
      induced muscle damage. Nine males participated in both a jogging and cycling
      protocol. RMR measurements were determined by indirect calorimetry before and on
      the seven mornings following three consecutive days of 45-min exercise sessions
      performed at equal energy expenditures. Daily protein intake and urinary nitrogen
      (N) output were measured throughout both protocols. No differences were observed
      in the resting oxygen consumption, respiratory exchange ratio, or heart rate
      between baseline measurements and from any of the postexercise days following the
      third exercise bout. Urinary N and the estimated N balance during postexercise
      also did not change from baseline values over time or mode x time. However, the
      overall estimated N balance for the jogging protocol was less positive than for
      the cycling protocol (p < 0.05). Muscular soreness was greater (p < 0.05) and
      lasted longer from the jogging protocol. Although, muscle damage may have been
      more severe in the jogging protocol, RMR and N balance were not different between
      the two exercise modes.

PMID- 7643579
TI  - Changes in blood ammonia and lactate levels during a triathlon race.
AB  - Blood ammonia and lactate concentrations were analyzed in 7 volunteer male
      athletes before and immediately after each segment of an endurance triathlon. The
      purpose of this study was to examine the effects of triathlon on ammonia and
      lactate blood levels and the possible correlation between both in each different
      event. Concentrations of blood ammonia were increased after each of the three
      segments, reaching a peak after the 40 km bicycle ride. Concentrations of blood
      lactate were also increased over baseline. However, there was a higher increase
      after the 1.4 km lake swim, than after the 40 km bicycle ride or after the 10 km
      run. No correlation was found between the levels of ammonia and lactate,
      suggesting that ammonia and lactate follow different metabolic patterns.

PMID- 7643580
TI  - Isokinetic torques and kicking maximal ball velocity in young soccer players.
AB  - The purpose of this study is to assess if there is any correlation between
      isokinetic testing and field performance of young soccer players. The isokinetic
      peak torques of the knee extensor muscles in sitting position (TKE), and those of
      the hip flexor muscles in standing position (THF) were measured in 24 junior
      soccer players. Four angular velocities (omega = 1.05, 3.14, 4.19, 5.23 rad.s-1
      or 60, 180, 240, 300 deg.s-1) were used for the knee extensors and three (1.05,
      3.14, 4.19 rad.s-1) for the hip flexors. On the field the subjects were asked to
      kick a stationary soccer ball as fast as possible against a barrier and the mean
      linear velocity over a 10 m path (v) was measured. TKE of the non dominant limb
      were higher than those of the opposite one at the three highest omega (p < 0.05).
      On the contrary the THF of the dominant limbs were higher than those of the
      controlateral, at the two highest omega. When the ball was kicked by the dominant
      or non dominant limbs, the mean values and standard deviations (+/- SD) of v were
      23.6 (+/- 2.5) and 21.4 (+/- 2.6) m.s-1. Torques and v were always positively
      correlated to each other; however, only in few cases was this relationship
      statistically significant. In conclusion the isokinetic torques do not seem to be
      good predictors of v, one of the several factors which determine the global
      performances of the soccer players.

PMID- 7643581
TI  - Performance characteristics of children using various braking resistances on the
      wingate anaerobic test.
AB  - This study examined the performances of children exercising against varying
      braking forces in short-term, all-out cycling tests. The braking force
      resistances were 0.04, 0.065, 0.075, and 0.08 kiloponds for every kilogram of
      body mass (kp.kgBM-1). Results for the peak and mean power performances in 30 s
      Wingate Anaerobic Tests (WAnT) were recorded for a wide age range of male and
      female children [6 (n = 23), 8 (n = 19), 10 (n = 19), and 12 (n = 14) years of
      age]. Univariate ANOVAs with repeated measures on resistance, and Newman Keuls
      post hoc analysis tests revealed that the absolute peak and mean power responses
      of the children increased incrementally with age and demonstrated very few sex
      differences. The overall meaned peak and mean power values of the four
      resistances and age groups were 161, 231, 242 and 248 Watts and 130, 183, 189,
      and 196 Watts, respectively. In all of the age groups the three higher
      resistances (0.065, 0.075, and 0.08 kp.kgBM-1) produced significantly higher peak
      and mean power performances than did the 0.04 kp.kgBM-1 resistance. The overall
      meaned relative peak and mean power values of the four resistances and age groups
      were 4.9, 6.9, 7.4 and 7.4 W.kg-1 and 4.2, 5.2, 5.7 and 6.2 W.kg-1, respectively.
      Among the three higher resistances there was no one resistance which elicited a
      significantly more powerful performance.

PMID- 7643582
TI  - Differences in physical characteristics in collegiate baseball players. A
      descriptive position by position analysis.
AB  - Physical characteristics including height, weight, body composition, and
      somatotype of NCAA Division II baseball players were evaluated to determine if
      differences in physical profiles exist by position at this level of competition.
      Differences in height, weight, lean body weight and somatoplots were found among
      various players. Pitchers were found to be taller that infielders and outfielders
      and displayed more endomorphy and less mesomorphy than the outfielders. Among the
      infielders, first basemen were taller than second basemen and third basemen while
      shortstops were found to be taller than second basemen. With respect to weight,
      first basemen and catchers were found to be heavier than second basemen. The
      second basemen had less lean body mass than all other infield groups. The data
      reveal more than a general description is warranted when describing the physical
      characteristics of baseball players at this level of play.

PMID- 7643583
TI  - Glucocorticoids in metabolic control during exercise: glycogen metabolism.
AB  - In order to evaluate the participation of glucocorticoids in the control of
      glycogen metabolism during exercise, experiments were performed on male
      adrenalectomized and normal rats. In adrenalectomized rats swimming for 4 hours
      induced less pronounced increases in lactate concentrations in skeletal muscles
      than in normal rats (in FG fibers up to 10.7 +/- 1.0 vs 14.8 +/- 1.2 and in SO
      fibers up to 9.1 +/- 0.7 vs 12.5 +/- 0.7 mg x g-1 wet tissue). The glycogen drop
      in liver and oxidative muscles was also less pronounced (in liver by 14% vs 52%,
      in SO fibers by 33% vs 54% in normal rats). Swimming until exhaustion led to an
      extremely low glucose level in blood (1.89 +/- 0.12 mMol x L-1) in
      adrenalectomized rats. When they were treated with dexamethasone, the swimming
      duration was longer (12 +/- 1 hours vs 9 +/- 0.8 hours in saline treated), blood
      glucose level at exhaustion was higher (3.07 +/- 0.23 mMol x L-1) and the drop of
      hepatic and muscle glycogen was more pronounced. In normal rats hepatic glycogen
      content dropped by 68% after swimming for 4 hours. After swimming for 8 or 12
      hours further decreases in hepatic glycogen content were insignificant. High
      levels of corticosterone in blood was found after swimming for 4 and 8 hours.
      After swimming for 16 hours corticosterone concentration was below normal and a
      new drop in liver glycogen (until a level constituting only 11% initial) was
      recorded. The results support the suggestion that glucocorticoids, regulate
      hepatic glycogen and peripheral glucose utilization during exercise, and also
      participate in the control of glycogenolysis in muscles.

PMID- 7643584
TI  - Anthropometric and somatotype variables related to strength in American football
      players.
AB  - The purpose of this study was to investigate the differences in somatotype, %
      fat, and strength in relation to body mass of two groups of American football
      players. One hundred and forty-three football players (85 high school and 58
      college) were classified into five weight groups (< 73 kg, 73-82 kg, 83-91 kg, 91
      100 kg, > 100 kg). Body composition was estimated from skinfold, and somatotype
      was determined using the Heath-Carter method. Strength was measured from one
      repetition maximum (1-RM) lifts in the bench press and deadlift. Most of the
      somatotypes were dominant mesomorphs for the high school player and
      endomesomorphs for the college player. The weight groups in both the high school
      and college footballer showed significant differences in % fat, somatotype, and
      strength measures between the lower and higher weight categories. Weight was a
      greater factor dictating strength in either lift in the high school player than
      in the college player. A higher mesomorphic component was a more important factor
      determining strength in the college player while a lower ectomorphic component
      contributed more in the high school player. The proportion of the variance
      accounted for by regression equations for the bench press and deadlift was 17% to
      41% in the high school player and 35% to 61% in the college player. Although
      football requires a large individual at certain positions, the question remains
      concerning overall size versus muscularity to achieve a superior performance
      level.

PMID- 7643585
TI  - Changes in physical activity are reflected in changes in fitness during late
      adolescence. A 2-year follow-up study.
AB  - The study describe changes over 2 years in different physical fitness measures
      and the relationship between these changes and changes in physical activity.
      Maximal aerobic work capacity (Wattmax), functional strength, muscle endurance,
      agility and flexibility were measured in 259 randomly selected high school boys
      and girls 16.5 years of age and followed-up 2 years later, while they still
      attended school. Most physical fitness measures increased over time in boys, and
      in girls an increase was found in arm extensor strength and trunk extensor
      endurance, but Wattmax per kg body mass decreased. Changes in physical
      performance between 16 and 18 years of age seem to be very similar in different
      countries, despite differences in physical activity patterns and absolute level
      of performance. No change was found in time of participation in physical activity
      or sports activity in either gender, but fewer girls participated in leisure-time
      sports at the 2nd test (p < 0.001). Change in physical activity or sports
      activity did not relate to change in physical fitness level. The relationships
      between level of sports participation (competition, for health or none) and
      physical fitness measures at baseline and at the 2nd test were weak or non
      significant. Three explanations for the weak relationship between physical
      activity and fitness are suggested: (A) part of the variability in fitness is
      explained by genetics, (B) growth and hormonal changes, especially in boys,
      override the stimulus of training, and (C) the physical fitness level in
      adolescents is so high that only physical activity at high relative intensity is
      supposed to have an effect on the fitness level.

PMID- 7643586
TI  - Personal incentives for exercise and body esteem: a canonical correlation
      analysis.
AB  - Two hundred twelve women and 93 men enrolled in physical education courses were
      administered the Personal Incentives for Exercise Questionnaire and the Body
      Esteem Scale. Canonical correlation was conducted. For women, it was determined
      that personal incentives for exercise have modest predictive power for the weight
      concern and physical conditioning dimensions of body esteem and very little
      predictive power for the sexual attractiveness dimension; the body esteem
      variates have slight predictive power for the competition and weight management
      dimensions of investment in exercise. For men, it was determined that personal
      incentives for exercise have modest predictive power for the physical
      conditioning dimension of body esteem, slight predictive power for physical
      attractiveness, and none for upper body strength; the body esteem variate has
      modest predictive power for the weight management dimension of incentives for
      exercise and slight predictive power for appearance and affiliation.

PMID- 7643587
TI  - Testing for inter-group contamination in a controlled longitudinal study of added
      physical education.
AB  - OBJECTIVE: This case report examines whether there was any cross-contamination
      between students enrolled in classes that received additional physical education,
      and their siblings who were enrolled in preceding and succeeding class-cohorts.
      EXPERIMENTAL DESIGN: A controlled longitudinal study extending over 6 years of
      primary school. SETTING: An urban and a rural primary school in Quebec.
      PARTICIPANTS: 546 primary students, comprising approximately equal numbers of
      boys and girls from the urban and the rural school. INTERVENTION: Entire class
      cohorts were given and hour of additional physical education ach day throughout
      their primary schooling, with immediately preceding and succeeding class-cohorts
      serving as controls. MEASURES: The measured data included standing height, body
      mass, maximal oxygen intake (direct treadmill test) and PWC170. RESULTS: We found
      no evidence of cross-contamination between siblings in experimental and control
      class-cohorts. CONCLUSION: Although a theoretical possibility, cross
      contamination between students in preceding and succeeding class-cohorts does not
      seem an important source of error in primary school students, presumably because
      such children prefer to play with friends from their immediate age cohort.

PMID- 7643588
TI  - Isolated partial tear of subscapularis muscle in a competitive water skier. A
      case report.
AB  - Partial tears of the subscapularis tendon associated with anterior shoulder
      dislocation, are frequently described while the isolated lesions of this tendon
      are quite rare. We report the case of a 33 years old water-skier who injured his
      right subscapularis muscle during a forced movement of adduction and internal
      rotation. Ultrasound evaluation and then MRI were used to depict the entity of
      the lesion. The ruptured tendon was surgically repaired using a MITEK anchor
      system. Four months after surgery, the athlete returned back to his full athletic
      activity.

PMID- 7643589
TI  - Efficacy of benidipine hydrochloride on myocardial ischemia and reperfusion.
AB  - The efficacy of benidipine hydrochloride in preventing myocardial ischemia and
      reperfusion injury was evaluated in isolated rabbit hearts (n = 28). Isovolumic
      left ventricular function, coronary flow, creatine phosphokinase (CPK) release,
      and myocardial water content were measured after ischemia during both
      normothermia (37 degrees C; Group I) and hypothermia (23 degrees C; Group II).
      After baseline measurements, hearts were induced to arrest by chilled
      cardioplegic solution. Each group was divided into two subgroups, depending upon
      whether benidipine hydrochloride (10(-9) mole/liter) was added in the
      cardioplegia (A, without benidipine; B, with benidipine). After 30 min of
      ischemia for Group I and 180 min for Group II (which added another cardioplegia
      every 30 min), hearts were reperfused. Measurements the same as those at baseline
      were carried out every 15 or 30 min for up to 60 min. Benidipine-treated hearts
      started beating in a shorter time than did control hearts (Group I-B, 38.7 +/-
      3.7 sec vs Group I-A, 59.9 +/- 5.6; Group II-B, 36.7 +/- 2.0 vs Group II-A, 47.8
      +/- 3.3). The percentage of recovery of left ventricular developed pressure after
      60 min of reperfusion was significantly better in benidipine groups (P < 0.05).
      With respect to changes in coronary flow and CPK release after reperfusion,
      benidipine groups were preserved extremely well. We conclude that the addition of
      benidipine hydrochloride to cardioplegic solution significantly improves
      ventricular function after myocardial ischemia and reperfusion.

PMID- 7643591
TI  - The effect of nitric oxide on fetal pulmonary artery smooth muscle growth.
AB  - Endothelium-derived nitric oxide (NO) relaxes fetal pulmonary arterial vessels
      through activation of guanylate cyclase and increasing smooth muscle cyclic
      guanosine 3', 5'-monophosphate (cGMP). Exogenous NO administered as a gas at low
      concentrations shares this effect, decreasing pulmonary artery resistance and
      increasing in pulmonary blood flow. NO, endogenously synthesized or inhaled as a
      gas, may affect cellular growth in the underlying pulmonary vascular smooth
      muscle media. We report the effects of NO and cGMP upon DNA synthesis and
      proliferation of passaged pulmonary vascular smooth muscle cells from fetal rats.
      Smooth muscle cells from rat fetal pulmonary artery (RFPASM; 18-19 day gestation;
      term 21 days) were treated in culture with sodium nitroprusside (SNP), isosorbide
      dinitrite (ISDN)--both NO-generating vasodilators--or 8-bromo-cGMP, a cell
      permeant cGMP analog. All agents inhibited thymidine uptake at concentrations of
      10(-3)-10(-2) M. Lower concentrations (10(-5)-10(-4) M) of SNP and ISDN increased
      [3H]-thymidine ([3H]TdR) uptake, an effect not seen with cGMP at similar
      concentrations. Exposing RFPASM to authentic NO gas in a deoxygenated medium
      inhibited [3H]TdR uptake only. NO appears to have a biphasic effect on DNA
      synthesis in passaged RFPASM, with stimulation at micromolar concentrations and
      inhibition at higher levels. NO may thus alter vascular smooth muscle growth and
      pulmonary vascular remodeling in conditions complicated by pulmonary hypertension
      and treated with inhaled NO.

PMID- 7643590
TI  - Alterations of lipid contents in blood, hepatocytes, and enterocytes in the early
      stage of acute liver failure induced by 90% hepatectomy in the rat.
AB  - Potential alterations in lipid metabolism in the early stage of acute liver
      failure are poorly elucidated. In the present study, acute liver failure was
      induced by subtotal hepatectomy (90%) in the rat in order to investigate early
      alterations in lipid contents in blood, hepatocytes, and enterocytes.
      Hypocholesterolemia and hypotriglyceridemia appeared 2 and 6 hr following
      subtotal hepatectomy. Plasma levels of high density lipoprotein-cholesterol were
      significantly lower in rats with acute liver failure than in controls, which may
      be associated with hypocholesterolemia. An increase in erythrocyte phospholipids
      and triglycerides was seen from 2 hr on after hepatectomy. The content of
      phospholipids and triglycerides was reduced in isolated enterocytes from the
      proximal small intestine and increased in enterocytes from the distal small
      intestine. Isolated hepatocytes from the remnant liver exhibited an increase in
      phosphatidylethanolamine and a decrease in phosphatidylinositol. Levels of
      enterocyte phosphatidylserine were elevated in both the proximal and the distal
      small intestine, while they diminished in the distal small intestine.
      Sphingomyelin content increased in the proximal small intestine. The recognition
      of lipid alterations in the intestine-liver-systemic circulation axis in the
      early stage of acute liver failure may be beneficial in improving the recovery
      from acute liver failure.

PMID- 7643592
TI  - Mast cell mediators and peritoneal adhesion formation in the rat.
AB  - We have previously shown that mast cell stabilization attenuates peritoneal
      adhesion formation in the rat. The present study investigated the mechanism of
      this protection. Adhesions were created in weanling rats using cecal scraping and
      application of 95% ethanol. Rats received specific blockers for the mast cell
      products histamine, serotonin (5HT), leukotriene D4, and platelet activating
      factor intraperitoneally 30 min before laparotomy and at the time of abdominal
      closure. Control animals received saline. Adhesions were assessed blindly 1 week
      later using a standardized scale. Adhesion formation was not affected by
      histamine blockade using combined mepyramine and ranitidine, 5-HT1 blockade using
      methysergide, 5-HT3 blockade using ondansetron, leukotriene D4 blockade using MK
      571, or platelet activating factor blockade using WEB-2086. However, blockade of
      the 5-HT2 receptor using ketanserin resulted in significant dose-dependent
      attenuation of adhesions compared to saline. These data suggest that mast cells
      mediate peritoneal adhesion formation in the rat through release of serotonin
      acting on 5HT2 receptors. Further understanding of this process may lead to new
      strategies for the prevention of postoperative adhesions.

PMID- 7643593
TI  - A model for the study of wounds in normal elderly adults and patients with
      peripheral vascular disease or diabetes mellitus.
AB  - The purpose of the study was to test the hypothesis that significant delays in
      cutaneous wound healing could be demonstrated using standard wounds and high
      quality histological methods in patients with severe peripheral vascular disease
      (PVD) and/or diabetes mellitus (DM) compared to healthy elderly controls.
      Additionally, we proposed that standard wounds on the arms of elderly controls
      would heal more rapidly than comparable wounds on the legs. In order to test
      these hypotheses we developed and characterized a partial thickness wound model
      which could be used safely in human subjects. The study population consisted of
      25 elderly normal volunteers, 17 patients with PVD, and 24 patients with DM.
      Standard wounds were created using a Simplate II bleeding-time device. A total of
      309 wounds ranging in age from 1 to 25 days were determined to be suitable for
      analysis. A global index of wound maturity was developed based on selected
      epidermal and dermal events of repair which could be scored histologically. The
      superficial component (within 0.1 mm of the epidermis) and deep components of
      dermal wounds were analyzed separately. Simultaneously created arm and leg wounds
      were studied in 15 of the elderly controls. Transcutaneous partial pressure of
      oxygen (TcPO2) measurements were used to estimate the severity of cutaneous
      ischemia. Data analysis revealed that the most striking differences observed were
      in dermal events of repair. Control wounds were more mature than dermal wounds
      from patients with PVD (P < 0.05). A significant reduction in the number of
      neutrophils and macrophages (P < 0.05) was demonstrated in 7-day-old wounds of
      patients with PVD compared to controls. Patients with DM showed a similar trend
      of reduced wound maturity but it did not reach statistical significance. Wounds
      created in skin with TcPO2 > 20 were more mature than wounds with TcPO2 < or = 20
      (P < 0.05) and arm wounds were more mature than leg wounds (P < 0.01). The most
      significant difference noted in this wound model was that the superficial
      compartment of dermal wounds was significantly more mature than the deep
      compartment (P < 0.001). Good agreement was observed between two independent
      scorers of wound histology and no complications were noted in either patients or
      controls when using this human wound model. We conclude that the model described
      allows evaluation of both epidermal and dermal events of repair with relative
      safety even in patients with PVD and DM.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7643594
TI  - Monoethylglycinexylidide formation as an independent measure of warm hepatic
      ischemia and reperfusion injury.
AB  - An accurate serologic measure of hepatic function would be clinically useful in
      selecting donors for liver transplantation. An experimental model that
      incorporates varying lengths of total hepatic warm ischemia with reperfusion
      injury was utilized to compare serologic parameters and mitochondrial performance
      of oxidative phosphorylation in predicting hepatocellular injury.
      Monoethylglycinexylidide (MEGX) formation following bolus intravenous lidocaine
      injection was found to be significantly decreased (P < 0.0001) at all periods of
      ischemia when compared to that in nonischemic controls. A serum MEGX level of <
      50 micrograms/liter suggested severe hepatic damage. No correlation was found
      between MEGX level and liver viability as measured by animal survival. Serum
      transaminase (AST and ALT) levels demonstrated progressive, nonsignificant
      elevations with increasing length of ischemia (P = 0.0779 at the maximum ischemic
      time). Polarographic measurements of mitochondrial oxidative phosphorylation did
      not reveal a significant alteration in subcellular metabolism with prolonged
      ischemic time. These data highlight the comparative sensitivity of MEGX formation
      as an early quantitative measurement of hepatocellular injury during warm
      ischemia, although it was not predictive of organ viability.

PMID- 7643595
TI  - PAF-antagonist administration after hemorrhage-resuscitation prevents splenocyte
      immunodepression.
AB  - A number of studies have suggested that the inflammatory and chemotactic autocoid
      platelet activating factor (PAF), together with various cytokines, plays an
      important role in the pathophysiology of trauma, sepsis, and shock. However,
      little is known about PAF's contribution to the immunosuppression associated with
      hemorrhage. The aim of our study was, therefore, to determine if the use of a PAF
      antagonist following hemorrhage has any salutary effects on splenocyte lymphokine
      production. To study this, mice were bled to and maintained at a mean arterial
      pressure of 35 mm Hg for 60 min. The mice were then segregated into three groups
      and were resuscitated with shed blood plus lactated Ringer's solution (2x the
      volume of shed blood), containing either a potent PAF-antagonist (Ro 24-4736, a
      thienodiazepine) in dimethyl sulfoxide (DMSO) or DMSO-vehicle. Sham-operated mice
      received either DMSO-vehicle in saline or saline alone. Twenty-four hours
      thereafter the animals were sacrificed and splenocyte cultures established and
      stimulated for 48 hr with Con A (2.5 micrograms/ml). Supernatant lymphokine
      levels were determined by bioassay. The cellular release of interleukin-2 and -3
      (IL-2 and IL-3) by splenocytes was significantly depressed in the nontreated or
      vehicle-treated hemorrhaged animals compared to shams. Treatment with the PAF
      antagonist Ro 24-4736 restored IL-2 and IL-3 release values to levels comparable
      to those of the sham-operated animals. Thus, (1) PAF appears to play a
      significant role in hemorrhage-induced immunosuppression and (2) the use of a PAF
      antagonist to uncouple the PAF-generated feedback loops prevents the depression
      in splenocyte function following hemorrhage.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7643596
TI  - Calcium regulation of endothelial permeability to low-density lipoprotein.
AB  - Increasing clinical and experimental evidence suggests a multifunctional role of
      calcium in determining the response of the arterial intima to atherogenic
      stimuli. In this study, an endothelial cell (EC)-smooth muscle cell (SMC) bilayer
      model of the arterial wall was used to investigate the effect of calcium
      manipulation on the sequestration of 125I-labeled LDL within the subendothelial
      space. Bilayer cell cultures were exposed to EGTA (0.25-2.0 mM), ionophore A23187
      (5 x 10(-6) M), lanthanum chloride (0.1 mM), and trifluoperazine (TFP; 0.25
      microM). The movement of 125I-labeled LDL (10 micrograms/ml) through the
      endothelial barrier was measured, as was the binding and cellular uptake of 125I
      labeled LDL by each cell type. Extracellular Ca2+ chelation with EGTA and
      intracellular Ca2+ mobilization with A23187 both increased EC permeability to LDL
      (P < 0.05; P = 0.0001, respectively), while not significantly affecting EC
      binding or uptake of lipoprotein. Conversely, these agents increased SMC uptake
      of LDL (P < 10(-7); P < 10(-8), respectively). Calcium blockade with lanthanum
      chloride had the opposite effect, reducing EC permeability (P = 0.011) and SMC
      uptake (P < 10(-5)), while increasing EC uptake (P = 0.016). TFP, a calmodulin
      inhibitor, had an effect similar to A23187, although reducing SMC uptake of LDL
      (P = 0.015). Alteration of the calcium gradient across the plasma membrane
      appears to influence EC permeability. This effect may be stabilized by Ca2+
      blockade or calmodulin regulation of cytoplasmic Ca2+. Additional anti
      atherogenic effects of calcium blockade may include a reduction in SMC uptake by
      the SMC.

PMID- 7643597
TI  - Immunolocalization of FXIIIa+ dendritic cells in human burn wounds.
AB  - Dermal dendrocytes constitute a population of indigenous antigen-presenting cells
      that have been implicated in dermal inflammation and may have a role in wound
      healing. They are identified by expression of the transglutaminase coagulation
      Factor XIIIa (FXIIIa) and a perivascular distribution in the papillary dermis. In
      this study, we used immunohistochemistry to localize and characterize FXIIIa+
      cells in healing burn wounds. Wound specimens from Postburn Days 2, 3, 4, 5, 6,
      8, 9, 10, 11, 15, 30, and 49 were collected from 18 patients at the time of
      excision and grafting, processed for immunolabeling, and labeled with an antibody
      to FXIIIa. Tissue sections were also double-labeled with the anti-FXIIIa and with
      antibodies to CD68, specific for macrophages, CD45, specific for bone marrow
      derived cells, and proliferating cell nuclear antigen (PCNA) for proliferation.
      Antigen-presenting status was evaluated using an antibody to the major
      histocompatibility complex HLA-DR. The dermis subjacent to the tongue of
      proliferating epithelium at the wound edge had increased numbers of FXIIIa+
      dendritic cells compared to the cellular distribution in uninjured skin. FXIIIa+
      dendritic cells were absent from the burned dermis on all postburn days examined
      in this study. However, capillaries in the deep dermis had a FXIIIa+ granular
      staining pattern. CD68+ cells and CD45+ cells were present throughout the wound
      bed at all stages of healing, indicating an inflammatory cell response in the
      injured dermis. Antibodies to PCNA did not colocalize to FXIIIa+ cells,
      suggesting that the dermal dendrocytes were not proliferating. The antibody to
      HLA-DR localized to some, but not all of the FXIIIa+ dendritic cells.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7643598
TI  - Anticatabolic effect of the beta 2-agonist cimaterol in vivo in tumor-bearing
      animals.
AB  - Loss of lean body mass occurs in cancer and may adversely affect outcome. The
      beta 2-agonist cimaterol increases muscle mass and protein content in tumor
      bearing animals, in part by decreasing protein degradation, but the effect of the
      drug on protein synthesis remains uncertain. To determine the influence of
      cimaterol on protein synthesis, a methylcholanthrene sarcoma was transplanted sc
      into the dorsum of male Fischer-344 rats. After 3 weeks of tumor growth, tumor
      bearing and control animals received daily sc injections of the beta 2-agonist
      cimaterol (0.15 mg/kg) for 5 days. Rate of protein synthesis was measured using
      iv [3H]-phenylalanine (25 microCi/100 g body wt) and cold phenylalanine (150
      mumole/100 g body wt) in a flooding dose. Extensor digitorum longus muscles were
      harvested 10 min later, homogenized, and assayed for [3H]-phenylalanine uptake
      (bound) (dpm/mg muscle) and tissue-specific (free) radioactivity to determine
      protein synthesis rate (Ks: %/24 hr). There was a significant increase in protein
      synthesis rate in control and tumor-bearing animals receiving cimaterol compared
      to that in freely feeding, food-deprived, or matched-carcass-weight nontumor
      bearing controls, as well as compared to that in tumor-bearing controls. We
      conclude that the anabolic effects of cimaterol are due to both decreased protein
      degradation and increased muscle protein synthesis. Therefore, beta 2-agonists
      may prove useful in prevention and/or treatment of cancer cachexia.

PMID- 7643600
TI  - Influence of red blood cells on lung function in an ex vivo rat heart-lung model.
AB  - Crystalloid perfusates commonly are utilized for lung preservation in
      extracorporeal small animal lung models. However, the function of these grafts is
      limited. In a new ex-vivo rat heart-lung model the role of red blood cells added
      to the crystalloid perfusate was investigated. Heart-lung blocks were rapidly
      excised (n = 9, each group) and the blocks were connected to the extracorporeal
      perfusion circuit using Krebs-Henseleit solution (KH) or KH with washed bovine
      red blood cells (hematocrit 38%) (KHRBC). The lungs were ventilated with room
      air. The coronary system was perfused via the aortic root with oxygenated
      perfusate. The lungs were perfused via the right ventricle with deoxygenated
      perfusate (PO2 15 mm Hg). Venoarterial improvement of oxygenation, pulmonary
      vascular resistance (PVR), and peak inspiratory pressure (PIP) were continuously
      monitored for 50 min. At the end of the experiment the wet/dry (W/D) ratio was
      determined using the mediastinal lung lobe while the remaining lung was used for
      light microscopic (LM) evaluation. After 30 min of perfusion, lung function was
      significantly better in the KHRBC group (PVR (KH): 752 +/- 193 dyn*sec*cm-5;
      (KHRBC): 279 +/- 48 dyn*sec*cm-5; PIP (KH): 31 +/- 3.2 mm Hg; (KHRBC): 25.8 +/-
      1.9 mm Hg). In addition, lungs perfused with KHRBC showed significantly less
      edema than those perfused with KH only (W/D ratio (KH): 7.8 +/- 1.2; (KHRBC) 5.1
      +/- 0.6; LM (KH): 3.5 +/- 0.9; (KHRBC): 2.3 +/- 0.8). The use of red blood cells
      in KH perfusate improved functional and structural integrity.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7643599
TI  - Quantification of thyrotropin-releasing hormone changes and serotonin content
      changes following graded spinal cord injury.
AB  - Thyrotropin-releasing hormone (TRH) and serotonin (5-HT) are well known as
      neurotransmitters of descending bulbo-spinal tracts. 5-HT uptake caudal to (5-HT
      decreased) graded spinal lesions has been measured in rats and dogs and
      significantly correlated with the degree of cord injury. We studied 5-HT content
      via high-pressure liquid chromatography and radioimmunoassay measurements of TRH
      in dog spinal cord, both rostral and caudal, to 6 week T6 spinal transection (T)
      (n = 7) or T6 hemisections (H) (n = 7). Sham controls (n = 7) were used. Mean 5
      HT content values were (pmole/mg): rostral sham 1.25 +/- 0.02, caudal sham 1.35
      +/- 0.17, rostral T 2.65 +/- 0.36, caudal T 0.19 +/- 0.06, rostral H 2.1 +/-
      0.22, and caudal H 1.0 +/- 0.31. A significant decrease in 5-HT caudal to
      transection versus control (P < 0.001) was seen. A trend for decreased 5-HT
      caudal to hemisection versus control (P < 0.1) was also seen. Mean TRH levels
      (pg/mg protein) were: rostral sham 40.02 +/- 18.47, caudal sham 30.61 +/- 10.03,
      brainstem sham 18.9 +/- 5.13, rostral T 52.4 +/- 21.34, caudal T 3.52 +/- 1.87,
      brainstem T 19.25 +/- 4.11, rostral H 43.45 +/- 18.61, caudal H 14.24 +/- 5.7,
      and brainstem H 21.89 +/- 1.23. Significant decreases for caudal TRH transection
      versus controls (P < 0.001) and for caudal TRH hemisection versus controls (P <
      0.02) were seen. A significant difference between caudal hemisection and caudal
      transection TRH levels (P < 0.001) was seen.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7643601
TI  - Effect of enteric nonnutrient infusions on motor patterns in neurally intact and
      neurally isolated canine jejunum.
AB  - Previous work in our laboratory has shown that nonnutrient mechanical factors
      initiate changes in motility patterns in local and remote regions of the small
      intestine. Our aims were to determine how isolated duodenal and jejunoileal
      nonnutrient infusions alter interdigestive motor patterns locally and distantly
      and whether these effects are neurally mediated. Ten dogs were prepared with
      duodenal and proximal jejunal infusion and manometry catheters and a proximal
      jejunal diverting cannula. Five of these dogs served as neurally intact controls
      (Group 1) and five also underwent in situ neural isolation of the entire
      jejunoileum (Group 2: extrinsic denervation; disruption of enteric myoneural
      continuity with duodenum). After recovery, nonnutrient infusions at 0-15 ml/min
      for 5 hr into proximal duodenum or jejunum did not consistently affect cycling of
      the migrating motor complex (MMC). The period and duration of individual phases
      of the MMC and time to first phase III after the start of infusion were similar
      in both groups. In Group 2, duodenal characteristics (period and duration of
      phase II, time to first phase III) increased slightly with increasing rates of
      jejunal but not duodenal infusion. Motility indices, although greater in Group 2,
      were not altered by enteric infusions. Differing rates of nonnutrient enteric
      flow limited to duodenum or jejunoileum did not affect markedly local or distant
      motor patterns. Alterations in interdigestive motility patterns by postprandial
      nonnutrient intraluminal content are not mediated directly by intraluminal flow.

PMID- 7643602
TI  - Pharmacokinetic studies of intraaortic stop-flow infusion with 14C-labeled
      mitomycin C.
AB  - This pharmacokinetic study attempted to improve the exposure of gastrointestinal
      tract tissues to chemotherapy by increasing the transit time of a first pass of a
      drug through the vascular system. Bolus infusion of 9 mg mitomycin (MMC) mixed
      with 1 mg of MMC labeled by 50 microCi of 14C was performed in 18 mongrel dogs.
      Pharmacokinetics of MMC in peripheral, portal, and aortic blood were studied
      under different types of major vessel occlusion. Three dogs with intravenous
      infusion constituted a control group. In 15 dogs MMC was infused intraaortically
      with the catheter's tip at the level of the celiac and superior mesenteric
      artery. Vascular flow was controlled in four different ways for 30 min: Type I
      Type IV. In Type IV the abdominal aorta and vena cava inferior were occluded
      after surgical exclusion of all nongastrointestinal branches of aorta. Blood
      samples were obtained during a 90-min period. After solubilizing the samples, 14C
      labeled MMC activity was counted by a scintillation counter. For stop-flow
      infusion Type I, II, III, and IV, area under the curve (AUC) ratios for portal
      blood versus systemic circulation were 1.6:1, 2.9:1, 2.9:1, and 8.8:1,
      respectively (statistically significant for Types II, III, and IV). The highest
      value of AUC, peak MMC concentration, and lowest clearance in portal blood were
      achieved in SFI Type IV. Exposure to MMC was the greatest with SFI Type IV,
      making this type of aortic stop-flow infusion the most favorable mode of drug
      administration from a pharmacokinetic perspective.

PMID- 7643603
TI  - A network model of developmental gene hierarchy.
AB  - A network model of development governing the whole temporal and spatial hierarchy
      of early embryogenesis and pattern formation in Drosophila is introduced. The
      network is related to a neural network model, with its units being developmental
      genes mostly connected by the genes' DNA-binding products. The developmental
      network's agreement with predictions regarding architecture and function of the
      neural network provides adequate grounds for an analogy between the two. The
      model is tested through computer simulations--predictions compare favorably with
      experimental observations. The model not only incorporates a program of control
      at gene level, but also makes a direct connection with current molecular studies
      throughout the whole hierarchy of the early embryogenesis of Drosophila.

PMID- 7643604
TI  - Appearance of phase-locked Wenckebach-like rhythms, devil's staircase and
      universality in intracellular calcium spikes in non-excitable cell models.
AB  - In this paper we show that Wenckebach-like patterns of intracellular calcium
      concentration, [Ca2+]i, arise in non-excitable cell models when driven
      repetitively by the application of agonists that activate the phospholinositide
      signalling pathway. These patterns are similar to action potential responses
      observed in excitable cells when driven periodically by external current stimuli.
      A model exclusively studied in this paper is based on the receptor-operated model
      of Cuthbertson & Chay (1991, Cell Calcium 12, 97-108), which is formulated under
      the assumptions that phospholipase C is a GTPase activating protein and a build
      up of the GTP-bound alpha-subunit is a slow dynamic variable responsible for the
      refractory period. Similarities between [Ca2+]i response and action potential
      response make it possible to reduce the full dynamic system to a one-dimensional
      discrete equation designed for cardiac rhythms. The Devil's staircase constructed
      from both the dynamic traces and one-dimensional maps shows that the rules
      governing this staircase are indeed universal even in the agonist phase-locking
      system. This work thus provides a theoretical explanation for the appearance of
      blocked and delayed responses of [Ca2+]i spikes observed in the hepatocytes in
      response to pulsed phenylephrine agonist and, moreover, demonstrates the
      existence of universality in the agonist pulsed phase-locking system.

PMID- 7643605
TI  - Steady-state rate analysis: application to biological transport.
AB  - A novel method for defining the steady-state unidirectional rates of complex
      reactions has previously been developed (Wagg, 1988 Ph.D. Thesis, Monash
      University, Australia). This methodology is based upon the method of Wagg (1987,
      J. theor. Biol. 128, 375-385) for defining the steady-state unidirectional fluxes
      of chemical species through branched chemical, osmotic and chemiosmotic
      reactions. It offers a number of distinct advantages over existing approaches to
      steady-state rate analysis: it is relatively simple to apply to complex reactions
      and is readily amenable to computer-based application. The method is demonstrated
      by direct application to a number of hypothetical models for biological transport
      phenomena.

PMID- 7643606
TI  - Steady-state flux ratio analysis: application to biological transport.
AB  - A thermodynamically constrained method of flux ratio analysis, based upon a
      previously developed thermodynamic rate ratio equation has been developed. In
      this paper it is demonstrated that, for a complex reaction, application of the
      thermodynamic rate ratio equation may provide a useful tool for the
      interpretation of unidirectional flux data thought to be mediated by the
      reaction, provided that: (i) a clearly defined mechanism for the reaction has
      been proposed; (ii) a set of partial reaction components may be defined for the
      reaction from the proposed mechanism, with the rate ratio of at least one of
      these components being amenable to experimental measurement. This paper defines
      the conditions for which the rate ratio of a component reaction may be measured,
      and illustrates the basic principles underlying this approach to flux ratio
      analysis by direct application to a number of hypothetical mechanisms for
      biological transport phenomena.

PMID- 7643607
TI  - A flux ratio analysis of the Post-Albers mechanism of the sodium pump.
AB  - A thermodynamically constrained method of flux ratio analysis has been applied to
      the Post-Albers mechanism of the sodium pump to establish a relationship between
      the thermodynamic "boundary conditions" for the overall pump reaction and the
      unidirectional flux ratios for the pump-mediated fluxes of sodium and potassium.
      This relationship provides an experimental criterion for assessing whether or not
      the reactions associated with ion binding and dissociation to and from the pump,
      respectively, are close to equilibrium. Examination of experimental data from the
      current body of literature indicates that the above criterion is not satisfied
      for the sodium pump of human red blood cells under normal physiological
      conditions. On the basis of this result, it is concluded that within the context
      of a Post-Albers mechanism one or more of the ion binding and dissociation steps
      are not in rapid equilibrium with other such steps, at least not for the sodium
      pump of human red blood cells under normal physiological conditions.

PMID- 7643608
TI  - Alignment of molecular sequences seen as random path analysis.
AB  - We propose a generating functional method--random path analysis (RPA)--that
      generalizes the classical dynamic programming (DP) method widely used in sequence
      alignments. For a given cost function, DP is a deterministic method that finds an
      optimal alignment by minimizing the total cost function for all possible
      alignments. By allowing uncertainty, RPA is a statistical method that weights
      fluctuating alignments by probabilities. Therefore, DP maybe thought of as the
      deterministic limit of RPA when the fluctuations approach zero. DP is the method
      of choice if one is only interested in optimal alignment. But we argue that, when
      information beyond the optimal alignment is desired, RPA gives a natural
      extension of DP for biological applications. As an algebraic approach, RPA is
      computationally intensive for long sequences, but it can provide better
      parametric control for developing analytical or perturbational results and it is
      more informative and biologically relevant. The idea of RPA opens up new
      opportunities for simulational approaches and more importantly it suggests a
      novel hardware implementation that has the potential of improving the way a
      sequence alignment is done. Here we focus on deriving a mathematically rigorous
      solution to RPA both in its combinatorial form and in its graphical
      representation; this puts DP in logical perspective under a more general
      conceptual framework.

PMID- 7643609
TI  - The maximum information principle and the evolution of nucleotide sequences.
AB  - The probability distributions of bases in nucleotide sequences are deduced from
      the maximum information principle by maximizing the entropy (due to random
      mutation of bases) under certain constraints (Markovian entropy, G + C content,
      etc, due to selection). Two formulations are given with respect to different
      selective constraints. The deviations of theoretical distributions from
      experimental data are lower than 10% for most sequences. It is shown that the
      Lagrange multipliers change from species to species systematically--i.e.
      selective constraints correlate with evolution.

PMID- 7643610
TI  - A model for glycolytic oscillations based on skeletal muscle phosphofructokinase
      kinetics.
AB  - Existing models for glycolytic oscillations are not based on detailed
      experimental kinetics of the glycolytic enzymes. Here, a model is constructed to
      fit the kinetics of skeletal muscle phosphofructokinase with respect to
      variations in AMP, ATP, fructose-6-P, and fructose 1,6-P2 levels. A Monod-Wyman
      Changeux model for a tetrameric enzyme is considered. However, it is found that
      the kinetic data fit considerably better with an assumption of identical,
      independent subunits. With parameters that fit these data and with a previous
      model for the rest of glycolysis, product activation of phosphofructokinase leads
      to oscillations of glycolytic intermediates and [ATP] resembling those observed
      experimentally in muscle extracts. The period is several minutes. The model can
      also produce oscillations at neutral pH and with [ATP] representative of an
      intact cell. Under both conditions the mean concentrations and oscillations vary
      with the rate of glucose phosphorylation in a plausible manner only if some
      amount of glucose-6-phosphatase or glucose-6-P dehydrogenase activity is assumed
      or if hexokinase is inhibited by glucose-6-P. Also, the model can be reduced to
      two variables for ease of analysis and the oscillation mechanism thereby
      illustrated.

PMID- 7643611
TI  - Kinetic models for nucleocytoplasmic transport of messenger RNA.
AB  - Much is known about the mechanism by which mRNAs cross the nuclear envelope (the
      translocation stage of nucleocytoplasmic transport), but far less is known about
      the preceding (intranuclear migration/release) and succeeding (cytoplasmic
      binding) stages. Therefore, existing information suffices for articulating
      detailed kinetic models of translocation, but not models for the overall mRNA
      transport process. In this paper, we show that simple kinetic models of
      translocation can (i) accommodate data about nucleocytoplasmic distributions of
      endogenous transcripts; (ii) predict the overall effects on these distributions
      of effectors such as insulin and epidermal growth factor; (iii) throw some light
      on the mechanism(s) of action of the HIV-1 protein Rev and produce experimentally
      testable predictions about this mechanism; and (iv) account for the action of
      influenza virus NS1 protein. However, the simplest forms of translocation models
      apparently fail to account for some properties of viral regulators such as HIV
      Rev and adenovirus E1B-E4 complex. To elucidate these topics, less narrowly
      focused models of mRNA transport are required, describing intranuclear
      binding/release as well as translocation. On the basis of our examination of
      translocation models, we suggest some criteria that the requisite broadly based
      models must satisfy.

PMID- 7643612
TI  - Information theory analysis of the relationship between primary sequence
      structure and ligand recognition among a class of facilitated transporters.
AB  - Determining how specificity for a given ligand occurs among sequence and
      structurally related transporters is a fundamental problem in elucidating
      facilitated transport. It is likely that the specificity of a transporter for a
      ligand is defined by the primary amino acid sequence, and that different ligand
      specificities among highly related proteins are associated with variations in the
      amino acid sequence. To assist studies on the potential relationships between
      protein structure and ligand specificity, information theory was used to assign a
      measure that quantitates the importance of amino acid choice at individual sites
      in protein sequences based upon their variability. The approach allows for the
      transformation of a collection of multiply aligned sequences into a profile that
      provides a quantitative assessment of the relative frequencies of chemically
      similar residues at each site. Profiles generated from particular groups of
      proteins can be directly compared to profiles generated for other groups. These
      comparisons allow unique differences in the utilization of amino acids at
      individual sites to be identified as differences in information distribution. The
      approach was applied to the problem of identifying sites of the dopamine
      transporter which may play a role in distinguishing its ligand specificity and
      function from those of a related population of transporters for amino acid and
      amino-acid-like ligands. Several sites were identified that appear highly likely
      to distinguish the dopamine transporter from related proteins. Many of the sites
      identified were also found to be associated with predicted variations in local
      secondary and tertiary structure between the two classes of proteins.

PMID- 7643613
TI  - Male gamete output of asexuals and the dynamics of populations polymorphic for
      reproductive mode.
AB  - Most asexual plants retain male sexual function, albeit at levels much lower than
      their sexual counterparts. This phenomenon has not typically received full
      representation in mathematical models of the cost of sex. We formulate and
      analyze a genetic model of reproductive mode in order to study the evolutionary
      dynamics of populations consisting of both sexual and asexual individuals. Our
      model incorporates levels of production and fertility of male gametes produced by
      individuals that are asexual in their female function, that vary from zero to a
      level equal to that in a sexual individual. This encompasses a range of naturally
      occurring situations that has been beyond the scope of most previous theoretical
      studies. We show that the cost of sex is frequency-dependent in many biologically
      relevant situations. Consequently, the fitness advantage needed for sexuals to
      resist invasion by asexuals may frequently be much less than twofold. However,
      the fitness advantage required for sexuals successfully to invade an asexual
      population may be much higher. Moreover, the viability/fertility advantage
      required by sexuals to equal the fitness of asexuals is not necessarily equal to
      the intrinsic cost of sex, but may be greater when asexual individuals produce
      fertile male gametes. We also show that panmictic populations cannot be stably
      polymorphic for reproductive mode when fitnesses are constant, and that the
      conditions for the fixation of sexual or asexual genotypes are not affected by
      the degree of dominance at the locus determining reproductive mode. With
      frequency-dependence, and no possibility of stable polymorphism, the reproductive
      mode that finally evolves will, in many cases, depend upon the initial
      frequencies of asexual and sexual individuals.

PMID- 7643614
TI  - Saltationist and punctuated equilibrium models for the evolution of viviparity
      and placentation.
AB  - Vertebrate viviparity (live-bearing reproduction), placentation, and
      placentotrophy are widely assumed to have evolved as three successive,
      gradualistic transformations. From empirical data and predictive tests on lizards
      and snakes, this paper indicates that placentae and a degree of placentotrophy
      have evolved repeatedly as necessary correlates of viviparity, not as subsequent
      modifications. In addition, information derived from studies of anatomy,
      physiology, biogeography and systematics is used to evaluate new saltationist and
      punctuated equilibrium models for the evolution of viviparity. Phylogenetic
      reconstruction reveals that more than 100 squamate clades have made the
      transition to viviparity and placentation. However, various phenotypic
      intermediates postulated by the gradualistic model are either scarce or
      unrepresented among known forms, including those in which viviparity has evolved
      at specific and subspecific levels. Evolution in squamates seems to have produced
      a dichotomy between two evolutionarily stable patterns: (i) retention of weakly
      shelled or shell-free eggs to term (viviparity), with development of fully
      functional placentae; and (ii) deposition of shelled eggs at or near the limb bud
      stage of development (typical oviparity). Conflicting functional demands placed
      on eggshell morphology may constrain establishment of prolonged, oviparous egg
      retention as a viable, historically stable pattern. Alternatively, the costs of
      prolonged egg-retention associated with decreased female mobility or decreased
      fecundity may exceed the benefits in oviparous forms.

PMID- 7643615
TI  - Differential expression of a basic helix-loop-helix phosphoprotein gene, G0S8, in
      acute leukemia and localization to human chromosome 1q31.
AB  - A basic helix-loop-helix phosphoprotein gene, G0S8, was recently isolated by
      differential screening of cDNA from human blood mononuclear cells stimulated with
      a T cell mitogen and cycloheximide. In this study, G0S8 expression was examined
      in normal and malignant hematopoietic cells by Northern blot analysis and reverse
      transcription-polymerase chain reaction (RT-PCR). G0S8 expression was observed in
      most fresh samples of acute myelogenous leukemia (AML) (28/30) and most cases of
      adult acute lymphoblastic leukemia (ALL) (9/11) regardless of clinical
      classification. G0S8 mRNA was also detected in all cases tested of chronic
      myelogenous leukemia (CML) in blast crisis. However, G0S8 expression was not
      detected in CML patients in chronic phase, nor in normal bone marrow or other
      hematopoietic cells. G0S8 has been mapped using fluorescence in situ
      hybridization (FISH) to human chromosome 1q31, the same site reported for the B
      cell homolog BL34/1R20 and within a region implicated in the development of
      hematological malignancies. The consistent observation of G0S8 mRNA in patient
      samples of acute leukemia suggests that G0S8 expression may either play a role in
      leukemogenesis or represent a common consequence of dysregulated growth.

PMID- 7643616
TI  - Detection of 11q23/MLL rearrangements in infant leukemias with fluorescence in
      situ hybridization and molecular analysis.
AB  - Cytogenetic abnormalities of band 11q23 have been found in more than 50% of
      infant leukemias regardless of the phenotype. Using probes for the MLL gene at
      11q23, MLL rearrangements have been identified in 70-80% of all infant leukemias
      including virtually all of the cases with 11q23 translocations, as well as cases
      with apparently normal karyotypes. We reviewed the chromosomal pattern of 26
      cases of infant leukemias (12 ALL, 12 AML, two AUL). Eleven had 11q23
      translocations, five had other abnormalities, and 10 had a normal karyotype. To
      determine whether 11q23/MLL rearrangements were present in the leukemia cells of
      patients with a normal karyotype, we performed FISH and molecular studies of
      eight of these patients who had adequate material. Three were found to have
      11q23/MLL abnormalities, two of them detected by FISH; one ALL case had a
      t(11;19) (q23;p13.3), and one AML case had a t(11;19) (q23;p13.1). Retrospective
      review confirmed the presence of the t(11;19) in a small percentage of poor
      quality metaphase cells in both cases. A rearrangement of the MLL gene was
      detected by Southern blot analysis of leukemic cells from a third patient with
      ALL; one cell with a deletion of 11q23 was found on karyotypic review. Therefore,
      in our series the actual incidence of 11q23 abnormalities in infant leukemias was
      54% (14/26): 67% in ALL (8/12) and 50% in AML (6/12). Our findings suggest that
      most infant leukemias with apparently normal karyotypes that have a molecular
      rearrangement of the MLL gene are undetected subtle translocations.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7643617
TI  - Molecular analysis of 13 cases of MLL/11q23 secondary acute leukemia and
      identification of topoisomerase II consensus-binding sequences near the
      chromosomal breakpoint of a secondary leukemia with the t(4;11).
AB  - Rearrangements of the MLL (Mixed Lineage Leukemia) gene in the human 11q23
      cytogenetic locus have been detected in secondary (therapy-related) acute
      leukemias in patients who have received topoisomerase II inhibitors for prior,
      independent neoplasms. The topoisomerase II inhibitors implicated in MLL/11q23
      secondary leukemias all inhibit the religation step of reaction catalyzed by
      topoisomerase II. This results in the stabilization of a 'cleavable complex' with
      double-strand DNA breaks at the point of topoisomerase II binding. This raises
      the possibility that the cleavable complex participates in the translocation
      process in MLL/11q23 secondary leukemias. Here we report that the MLL/11q23
      breakpoints in 13/13 patients with secondary leukemia map to the same breakpoint
      cluster region (bcr) noted in de novo MLL/11q23 acute leukemias and the presence
      of in vivo topoisomerase II inhibitor-induced cleavage sites in MLL/11q23 bcr. We
      have also cloned and sequenced the breakpoint from a MLL/11q23 secondary acute
      leukemia. This analysis revealed sequences similar to the consensus sequence for
      vertebrate topoisomerase II binding and cleavage close to the 11q23 and 4q21
      breakpoints. These results support a role for topoisomerase II in mechanism
      generating translocations in MLL/11q23 secondary acute leukemia.

PMID- 7643618
TI  - Rearrangement of proximal 11q13 band in a CMML in acute transformation.
AB  - Fluorescence in situ hybridization (FISH) was performed on bone marrow cells
      thought to contain a t(7;11)(p22;q13) from a patient with chronic myelomonocytic
      leukemia in transformation. FISH analysis using a panel of 10 probes previously
      mapped to 11q13 revealed a cytogenetically undetected complex rearrangement that
      involved chromosomes 7 and 11 as well as a chromosome 3 at band p24. Two distinct
      translocation breakpoints, both proximal to the BCL1 locus, were found in
      chromosome 11 that perforce separate it into three subregions. The two
      breakpoints appear distinct from the two previously described ones which involved
      the FAU and GSTP1 genes. Our observations add to the involvement of proximal
      11q13 in myeloid malignancies.

PMID- 7643619
TI  - Specific immunologic recognition of the tumor-specific E2A-PBX1 fusion-point
      antigen in t(1;19)-positive pre-B cells.
AB  - The t(1;19) translocation is the most commonly observed chromosomal translocation
      in childhood acute lymphoblastic leukemia (ALL). Its presence among pre-B cell
      ALL cases, has been associated with a poor prognosis. Two genes, E2A and PBX1,
      are involved in this t(1;19) translocation. As a consequence, parts of the E2A
      and PBX1 genes are fused, resulting in a chimeric E2A-PBX1 gene, encoding
      chimeric E2A-PBX1 proteins. As such, the amino acid sequence at the fusion site
      represents a unique tumor-specific determinant. We report on the generation of a
      polyclonal antiserum, termed BP 1/19, raised against the tumor-specific E2A-PBX1
      junction of E2A-PBX1 proteins. The specificity of antiserum BP 1/19 for the E2A
      PBX1 fusion-point is demonstrated at the peptide and at the protein level.
      Furthermore, specific binding of antiserum BP 1/19 to t(1;19) positive cells was
      shown using immunofluorescence techniques. The study shows that: (1) the tumor
      specific fusion-point epitope on E2A-PBX1 proteins is presented in an antigenic
      fashion, and (2) this particular fusion-point epitope can be used in
      immunological marker analysis using fluorescence microscopy.

PMID- 7643620
TI  - The human thrombopoietin gene is located on chromosome 3q26.33-q27, but is not
      transcriptionally activated in leukemia cells with 3q21 and 3q26 abnormalities
      (3q21q26 syndrome).
AB  - We previously demonstrated that the EVI-1 gene was transcriptionally activated in
      the 3q21q26 syndrome and chromosomal breakpoints at 3q26 were clustered within
      400 Kb of the EVI-1 gene. Since thrombocytosis is often observed in the 3q21q26
      syndrome, we first mapped the thrombopoietin (TPO) gene and then we examined for
      transcriptional activation and chromosomal rearrangement of the TPO gene in four
      cases of the 3q21q26 syndrome. The TPO gene was assigned to chromosome 3q26.33
      q27 by fluorescence in situ hybridization analysis. Although the TPO gene was
      mapped to the same locus as the EVI-1 gene, the distance between the TPO gene and
      the EVI-1 gene at 3q26 was more than 600 Kb and no gross chromosomal
      rearrangements of the TPO gene were detected by Southern blot analysis and pulsed
      field gel electrophoresis (PFGE) analysis. TPO transcripts were not detected in
      these leukemia cells by Northern blot analysis. These results indicate that
      activation of the TPO gene is not the main cause of thrombocytosis in the 3q21q26
      syndrome.

PMID- 7643622
TI  - ATL cells recognize self class II HLA antigens: implication to leukemogenesis.
AB  - Adult T cell leukemia (ATL) cells show the decreased expression of T cell
      receptor (TCR)/CD3 complex on their surfaces in vivo. It is well known that
      excess amounts of antigen modulate TCR/CD3 complex on antigen-specific T
      lymphocytes. We hypothesized that antigen receptor of ATL cells was down
      regulated with some antigenic stimulation in vivo, which might play an important
      role in leukemogenesis. In order to test this possibility, we studied whether the
      fresh ATL cells from three cases would respond to autologous and allogeneic
      lymphoid cell lines. In two of three cases, ATL cells could proliferate in the
      presence of autologous cell lines. In one case, this proliferation could be
      completely inhibited by anti-CD3 and anti-human leukocyte antigen (HLA)-DQ
      monoclonal antibodies, indicating that ATL cells recognized self HLA-DQ. In
      another case, the proliferation was suppressed by anti-CD3 and HLA-DR antibodies.
      These findings showed that ATL cells of some cases were derived from autoreactive
      T lymphocytes and such stimulation via TCR/CD3 complex plays an important role in
      the leukemogenesis of ATL in vivo.

PMID- 7643621
TI  - Characterization and regulatory effect of gamma-glutamyltransferase messenger RNA
      untranslated regions in human leukemia.
AB  - In this paper we report the presence and function of the 5' untranslated region
      (5'UTR) from the mRNA encoding human gamma-glutamyltransferase (GGT) in three
      different hematopoietic cell lines (HL-60, U-937 and K-562) as well as in the RNA
      of the leukocyte fraction from six acute lymphoblastic leukemias (ALL). Results
      obtained by RNase protection analysis demonstrate the presence of a unique form
      of 5'UTR expressed in most human tissues. In order to investigate the possible
      role of this type of sequence on regulation of GGT in hematopoietic cells,
      plasmid constructs carrying human hepatoma GGT 5'UTR and a luciferase reporter
      gene were transfected into the three blood cell lines. Compared to control
      untransfected cells, transfected HL-60 and K-562 showed a decrease in reporter
      gene activity of 51 and 73%, respectively. In contrast, transfected U-937 showed
      a 139% increase of reporter gene activity. Results were compared to GGT activity
      in the relevant cells and we concluded that the 5'UTR appears to have a
      regulatory role in GGT expression as a tissue-specific modulator of translation.

PMID- 7643623
TI  - Recognition of peptides corresponding to the joining region of p210BCR-ABL
      protein by human T cells.
AB  - In chronic myeloid leukemia (CML) the proto-oncogene c-abl from chromosome 9 q34
      is translocated to the breakpoint cluster region (bcr) gene on chromosome 22 q11.
      This translocation results in a BCR-ABL fusion gene, which encodes chimeric
      fusion oncoproteins p210BCR-ABL. Here we demonstrate that a peptide with joining
      region sequence ATGFKQSSKALQRPVAS (eight amino acids (aa) encoded by BCR exon 3;
      one novel lysine, encoded by the fusion codon; eight aa encoded by ABL exon 2) is
      immunogenic to human T cells. Primary immune response induction with this peptide
      resulted in a HLA DR2(DRB1*1501) restricted CD4+ BCR-ABL peptide specific T cell
      line P1. Responses of P1 were negatively affected by individual aa replacement by
      alanine at eight aa positions within the 17mer peptide (F4, K5, Q6, K9, L11, Q12,
      R13, P14). These findings were supported by experiments with a panel of
      overlapping 11mer b3a2 peptides. Only two of these peptides with an aa sequence
      encompassing all residues which could not be replaced by alanine induced P1
      proliferation. Since presentation of cytosolic oncoproteins as peptides by DR
      molecules has been observed, the present findings provide a possible explanation
      for post interferon-alpha persisting remissions in spite of the presence of BCR
      ABL PCR positive progenitors.

PMID- 7643624
TI  - Use of quantitative polymerase chain reaction to monitor residual disease in
      chronic myelogenous leukemia during treatment with interferon.
AB  - Interferon-alpha (IFN-alpha) has become a widely used treatment modality in
      chronic myelogenous leukemia (CML) and was shown to induce complete hematologic
      responses in about 70% of the patients. In a minority of cases, complete
      suppression of the Philadelphia (Ph)-positive clone has been observed by
      cytogenetic investigation or by Southern blot analysis. In most instances,
      however, analyses by the highly sensitive two-step polymerase chain reaction
      (PCR) reveal the presence of residual leukemic cells despite continuous
      treatment. Since PCR positivity has not been associated with an increased risk of
      disease recurrence, the monitoring of cells carrying the characteristic BCR/ABL
      rearrangement by qualitative PCR may not facilitate early identification of
      patients who are likely to relapse. We have therefore employed a quantitative PCR
      technique to monitor the BCR/ABL mRNA expression levels during the course of
      treatment in an attempt to assess the response to IFN-alpha at the molecular
      level and to provide a basis for early detection of progressive disease. Twenty
      CML patients who received therapy with IFN-alpha in first chronic phase of the
      disease were enrolled in the study. In addition, we have monitored two CML
      patients treated with IFN-alpha for relapse after bone marrow transplantation.
      Thirteen patients who displayed decreasing, constant or fluctuating levels of
      BCR/ABL expression during an observation period of up to 4 years (mean 25 months)
      have remained in hematologic remission. Two patients showed an elevation in the
      marker gene expression upon discontinuation of treatment, but no further increase
      in BCR/ABL mRNA has been observed after reinitiation of therapy with IFN, and the
      patients have remained in hematologic remission. In seven patients, quantitative
      PCR (Q-PCR) analyses revealed increasing expression of the chimeric gene during
      treatment with IFN-alpha. In all seven cases, the detection of elevated BCR/ABL
      transcripts by quantitative PCR preceded signs of hematologic or cytogenetic
      disease progression by up to 8 months (median 6 months). Our data show that
      quantitative PCR analysis facilitates the monitoring of the response to IFN-alpha
      therapy and provides an effective diagnostic tool for the timely detection of
      recurrent disease. The employment of this technique greatly enhances the
      diagnostic possibilities in the management of chronic myelogenous leukemia.

PMID- 7643625
TI  - In vitro study of THP-doxorubicin retention in human leukemic cells using
      confocal laser microspectrofluorometry.
AB  - Microspectrofluorometry allows the analysis of fluorescent molecules such as
      anthracyclines in the nucleus of isolated living cells. Using this technique, we
      confirmed that the amount of doxorubicin or THP-doxorubicin incorporated into the
      nucleus was related to the resistant or sensitive character of K562 cells. It was
      then extended to the study of fresh leukemic cells and kinetic studies were
      performed allowing the calculation of the retention rate (RR) of anthracycline
      (THP-doxorubicin) into the cell nucleus. A reproducibility study confirmed the
      accuracy of the method. Blast cells collected in patients with acute myeloid (n =
      22) or lymphoid (n = 8) leukemia, at diagnosis (n = 26), or in relapse (n = 4)
      have been studied. RR varied from 8 to 98% independently of the type of leukemia
      or the clinical status. RR did not correlate either with P-glycoprotein or with
      CD34 expression although this latter result should be confirmed on a higher
      number of subjects. Among 18 patients presenting with AML at diagnosis, 14 have
      been treated with intensive chemotherapy including anthracyclines; the only one
      who had resistant disease had the lowest RR value. In conclusion, the results
      obtained here show that microspectrofluorometry allows the performance of kinetic
      studies on fresh leukemic cells in order to quantify chemo-resistance phenomena
      related to drug transport.

PMID- 7643626
TI  - Expression of FLT3 receptor and FLT3-ligand in human leukemia-lymphoma cell
      lines.
AB  - The FLT3 gene encodes a receptor tyrosine kinase that is closely related to two
      well-known receptors, KIT and FMS, that regulate with their respective ligands,
      stem cell factor (SCF) and macrophage colony-stimulating factor (M-CSF),
      proliferation and differentiation of hematopoietic cells. The ligand for FLT3,
      FL, is active in both soluble and membrane-bound forms. We examined expression of
      FL and FLT3 mRNA in a panel of some 110 continuous human leukemia-lymphoma cell
      lines from all major hematopoietic cell lineages by Northern blot analysis. FLT3
      mRNA is expressed primarily in pre-B cell lines, myeloid and monocytic cell lines
      whereas FL mRNA was detected in most cell lines from all cell lineages. Analysis
      of FLT3 receptor protein expression examined with a specific anti-FLT3 monoclonal
      antibody and flow cytometry in 17 cell lines confirmed the results obtained at
      the mRNA level. Forty of 110 cell lines displayed both receptor and ligand mRNA
      suggesting a possible autocrine or intracrine stimulation. In normal
      hematopoietic cells expression of FLT3 was reported to be associated with CD34
      positivity, a cell surface marker of immature and precursor cells. No correlation
      between FLT3 and CD34 expression was found in the cell lines analyzed. These
      studies served to illustrate further the importance of the FL-FLT3 ligand
      receptor system in the regulation of hematopoietic cells.

PMID- 7643627
TI  - Retinoic acid and phorbol ester induced hyperphosphorylation of topoisomerase II
      alpha is an early event in HL-60 human leukaemia cell differentiation: effect on
      topoisomerase activity and etoposide sensitivity.
AB  - Treatment of HL-60 with phorbol myristate acetate (PMA) for 30 min, or all-trans
      retinoic acid (RA) for 60 min, results in hyperphosphorylation (3-5x) of
      topoisomerase II (p170, topo II) in vivo. RA and PMA activate a coprecipitating
      kinase, respectively inducing 1.6 and 2.7-fold increases in phosphorylation of
      topo II in immunoprecipitates. The activity of the co-precipitating kinase is
      inhibited by heparin and unlabelled GTP suggesting that casein kinase II (CKII)
      is, at least in part, responsible for the topo II hyperphosphorylation in
      response to differentiation signals. Although following dephosphorylation of the
      enzyme with alkaline phosphatase there was virtual abrogation of activity, the
      differentiation associated hyperphosphorylation had little impact on the
      decatenation activity of topo II in nuclear extracts. There were, however
      detectable changes in topo II function in vivo which affected the formation of
      the etoposide stabilised cleavable complex, but only after PMA treatment. PMA
      resulted in a rapid reduction in etoposide induced cleavage, 30 min treatment
      with PMA reducing cleavage by 20%. However, treatment with RA for 1 or 2 h when
      hyperphosphorylation was maximal did not affect cleavage. Immunoband depletion
      assays suggested that differentiation associated changes in chromatin structure
      rather than alterations in the enzyme per se are responsible for the reduction in
      cleavable complex formation following PMA treatment. Etoposide cytotoxicity was
      significantly reduced following just 30 min PMA treatment, but not reduced and
      even possibly enhanced by retinoic acid treatment. These findings are relevant
      not only to the dissection of the role of topo II in differentiation but also to
      its exploitation as a therapeutic target.

PMID- 7643629
TI  - Leukemia after true histiocytic lymphoma: another type of acute monocytic
      leukemia with histiocytic differentiation (AML-M5c)?
AB  - The case of a 44-year-old man diagnosed of a true histiocytic lymphoma who, after
      autologous bone marrow transplantation, developed leukemia with histiocytic cells
      is reported. Morphologic, cytochemical, immunophenotypic and genotypic
      characteristics of malignant cells are described, and the literature about this
      and related entities is reviewed. In addition, comparison with a recent report of
      malignant histiocytosis with leukemic involvement is established and its
      inclusion in the recently proposed subtype of monocytic leukemia with histiocytic
      differentiation (M5c), suggested.

PMID- 7643630
TI  - Osteoclast precursors circulate in the peripheral blood of patients with
      aggressive multiple myeloma.
AB  - Osteolysis resulting in extensive bone damage is a major clinical manifestation
      of patients with multiple myeloma (MM). The mechanisms of bone resorption in MM
      are incompletely understood. The final pathway is the generation of activated
      osteoclasts within bone marrow (BM) microenvironment. To investigate the
      mechanisms of bone resorption in MM we established an experimental system that,
      including bone marrow (BM) stromal cells and bone slices, closely mimicks in
      vitro the in vivo BM microenvironment. Peripheral blood mononuclear cells (PBMC)
      from nine patients with MM, three monoclonal gammopathy of undetermined
      significance (MGUS), and nine normal controls were cultured in this system. PBMC
      from patients with aggressive and bone devastating MM gave rise to multi
      nucleated cells with the morphology and phenotype of osteoclasts. These cells
      induced bone resorption in vitro which was inhibited by the addition of
      calcitonin. No bone resorption was observed in cultures of PBMC from patients
      with MM and limited bone damage, with MGUS and from normal subjects. These
      findings indicate that patients with aggressive MM have a population of
      circulating precursors that develop into functionally active osteoclast-like
      cells once they come in contact with the BM microenvironment. These cells may
      contribute to the wide-spread and generalized bone erosion observed in the
      patients.

PMID- 7643631
TI  - Detection of P-glycoprotein with a rapid flow cytometric functional assay using
      Fluo-3: evaluation of sensitivity, specificity and feasibility in multiparametric
      analysis.
AB  - The specificity and sensitivity of a flow cytometric assay simultaneously
      measuring expression and transport function of the multidrug resistance
      associated P-glycoprotein (Pgp) was evaluated. The monoclonal antibody (mAb),
      MRK16 was used to detect phenotypic Pgp expression while Fluo-3-AM was used as a
      fluorescent substrate in a Pgp functional transport assay. The specificity of the
      functional assay was examined in two vinblastine selected human leukemic cell
      lines (K562/VLB2.5 and CCRF-CEM/VLB50) with acquired Pgp overexpression.
      Downmodulation of Pgp function in these cell lines could be demonstrated with
      different substances (verapamil, vinblastine, trifluoperazine, cyclosporin A,
      progesterone and quinidine) and was proven to be consistently higher in the
      vinblastine selected cells than in their non-selected drug sensitive
      counterparts. Unexpectedly, modulator activity was also observed in drug
      sensitive K562 and CCRF-CEM cell lines despite the inability to detect Pgp in
      those cells by MRK16 flow cytometrically. Low level expression of the MDR1 gene
      encoding Pgp in sensitive K562 cells was however demonstrated with a sensitive RT
      PCR procedure. The small effect of Pgp modulators in non-drug selected cells
      could therefore be attributed to low level basal expression of Pgp and
      illustrates the sensitivity of the functional assay. Also, the effect of various
      Pgp modulators on Pgp function was more pronounced in a subpopulation of Pgp
      expressing lymphocytes than in lymphocytes which did not express Pgp. Finally, a
      correlation was found between discrete variations in Pgp expression and Pgp
      function of CD4+ lymphocytes, underscoring the feasibility of the functional
      assay in a triple parametric procedure. The triple parametric assay holds promise
      to detect Pgp expression and function in clinical samples containing mixtures of
      malignant and non-malignant cells.

PMID- 7643628
TI  - Expression of cell cycle regulatory proteins in chronic lymphocytic leukemias.
      Comparison with non-Hodgkin's lymphomas and non-neoplastic lymphoid tissue.
AB  - The expression of certain cell cycle regulatory proteins: cdk1, cdk2, cdk4,
      cyclin A, cyclin B, cyclin E, Bcl2 and PCNA was examined in peripheral blood
      lymphocytes (PBL) from 25 cases of chronic lymphocytic leukemias (CLL) in order
      to analyze a possible cell cycle involvement of CLL lymphocytes. For comparison,
      we also studied the expression of these proteins in: 23 samples of non-Hodgkin's
      lymphoma (NHL) tissue of different histological types, 10 samples of non
      neoplastic lymphoid tissue (NLT), non-stimulated PBL (NS-PBL) and PHA-stimulated
      PBL (PHA-PBL) from three healthy donors. Samples were lysed and proteins were
      resolved on polyacrylamide gel followed by Western blot. The expression of cdk4
      and cyclin E, both known to act in early cell cycle stage, was approximately on
      the same level in all groups of lymphoid pathology examined. In particular, we
      found that that 19 out of 24 CLL cases were cyclin E positive and all but one
      were cdk4 positive, ie they expressed these markers over twice the level of non
      stimulated healthy PBL. The cdk1 expression was above the level seen in NS-PBL in
      14 (56%) cases, but the average expression was significantly lower than in the
      other tissues examined, including low-grade lymphomas. Cdk2 expression was
      comparable in CLL and in low malignancy grade NHL, but weaker than in other NHL
      and in NLT. Cyclins A and B, normally observed in advanced cell cycle phases,
      were not seen in any CLL case. The presence of cdk4 and cyclin E in the blood
      cells of the majority of CLL cases studied, as well as cdk1 and cdk2 in some
      cases, indicate that the CLL cells are not quiescent, but are blocked in an early
      stage of the G1 cell cycle phase, and/or that the expression of these proteins is
      pathologically deregulated.

PMID- 7643632
TI  - Reply to Haas: Are ABL and BCR imprinted? (Leukemia 1995; 9: 740-743).

PMID- 7643633
TI  - All-trans retinoic acid (ATRA) administration during pregnancy in relapsed acute
      promyelocytic leukemia.

PMID- 7643634
TI  - A simple method for 'rescuing' clotted bone marrow samples for cytogenetic
      investigations.

PMID- 7643635
TI  - Utilization and outcomes of surgical gastrostomies and jejunostomies in an era of
      percutaneous endoscopic gastrostomy: a population-based study.
AB  - OBJECTIVE: To determine the indications for use of surgical gastrostomy (SG) and
      surgical jejunostomy (SJ) as feeding tubes, the complications, and the trends in
      the use of SG and SJ after the introduction of percutaneous endoscopic
      gastrostomy (PEG) at our institution in 1981. DESIGN: We conducted a
      retrospective, population-based cohort study of residents of Olmsted County,
      Minnesota, who received surgically placed feeding tubes between 1976 and 1989.
      MATERIAL AND METHODS: The medical records of all Olmsted County residents with
      surgical placement of a feeding tube during the designated study period were
      reviewed, and underlying conditions, complications, and survival were analyzed.
      RESULTS: Of 77 adult patients (mean age, 66 years; 48% women), 54 underwent SG
      and 23 had SJ. General anesthesia was used in 42 patients (55%). The indications
      for SG or SJ were stroke in 23 patients, cancer in 19, other central nervous
      system-related conditions in 16, and other conditions in 19. Among the numerous
      comorbid conditions, pulmonary disease (N = 44) and cardiac disease (N = 32) were
      most frequent. The median duration of follow-up was 181 days. Complications
      occurred in 31 of 54 patients (57%) with SG and in 13 of 23 (57%) with SJ. Of the
      117 complications, 15% were considered major. Twenty patients (26%) resumed
      eating. Survival at 1, 6, and 12 months was 79%, 49% and 36%, respectively. Most
      deaths were due to the disease for which the feeding tube had been placed. In a
      Cox proportional hazards regression analysis, only age and hypoxemia were found
      to be significantly associated with survival. Hypoxemia, type of tube, central
      nervous system disease as indication for procedure, and previous aspiration were
      associated with failure to resume eating (P < 0.05). Survival was similar to that
      for our patients with PEG during the same period. The overall incidence of
      feeding tube placement increased throughout the study period. CONCLUSION:
      Patients who require enteral feeding tubes have multiple comorbid conditions that
      have a major influence on the outcome. The overall incidence of feeding tube
      placement increased after the introduction of PEG. In patients who require long
      term enteral nutrition and are unable to have a feeding tube placed
      percutaneously, surgically placed feeding tubes have outcomes similar to those
      reported for patients with PEG.

PMID- 7643636
TI  - Incidence of sudden infant death syndrome in Olmsted County, Minnesota: 1945
      through 1992.
AB  - OBJECTIVE: To apply uniform diagnostic criteria for sudden infant death syndrome
      (SIDS) for an extended period for comparison of incidence rates from 1945 to 1992
      in Olmsted County, Minnesota, to investigate the influence of a person-time or
      live birth denominator on the estimate of incidence, to calculate the
      proportionate mortality rate for SIDS over time, and to evaluate the accuracy of
      death certificates for case ascertainment and the role of interobserver variation
      in case classification. DESIGN: We retrospectively reviewed the autopsy results
      and complete medical records for all infant death from 1945 through 1992 for
      residents of Olmsted County, Minnesota. MATERIAL AND METHODS: Cases were
      identified from a computerized list of all Olmsted County deaths of infants
      occurring at ages 48 hours to 365 days. All resident cases were categorized as
      non-SIDS, possible SIDS, SIDS, or incomplete, on the basis of findings from
      autopsy and clinical history. Incidence rates were calculated for two different
      SIDS groups and with use of denominators of person-time and live births. RESULTS:
      For the study period, 82 cases of SIDS were identified (97% white and 3% Asian).
      The mean age at death was 12.5 weeks; male infants constituted 59% of cases. No
      significant trend in seasonal distribution was noted; 73% of deaths occurred
      between midnight and noon. The incidence rate, defined as SIDS definite and
      possible deaths per 1,000 resident live births, increased from 0.55 in 1950
      through 1953 to 1.28 in 1990 through 1992. The secular trend was best described
      by a linear model with constant positive slope. Similar trends were observed with
      other definitions of incidence. During the study period, SIDS as a percentage of
      total infant deaths dramatically increased, ranging from 2.5 in 1950 through 1953
      to 17.9 in 1990 through 1992. The death certificate diagnosis correctly predicted
      72% of SIDS cases before 1970 and 100% of cases after 1970. CONCLUSION: Since
      1945, the incidence of SIDS apparently has increased, although diagnostic
      transfer from other causes of death probably contributes to the observed trend.
      The comparison of live births versus person-time as denominators showed no
      significant difference in incidence rates. Interobserver reliability is modest
      for SIDS cases diagnosed before 1970 and may contribute to the variability in
      reported SIDS incidence rates.

PMID- 7643637
TI  - Laparoscopic left adrenalectomy for aldosteronoma: early Mayo Clinic experience.
AB  - OBJECTIVE: To evaluate early results with laparoscopic left adrenalectomy in
      patients with an aldosteronoma. DESIGN: We retrospectively reviewed the medical
      records to Mayo patients in whom laparoscopic left adrenalectomy had been
      attempted for presumed aldosteronoma. MATERIAL AND METHODS: Data on the
      diagnosis, details about the procedure, occurrence of associated complications,
      and duration of recovery period were analyzed for all study patients. RESULTS: Of
      the nine patients who underwent attempted laparoscopic left adrenalectomy, seven
      had aldosteronoma. In six of the seven patients, the procedure was successful. No
      preoperative mortality occurred, and morbidity was limited to prolonged ileus in
      one patient. Of the other five patients with successful results, all tolerated
      liquids within 24 hours after the procedure. The mean postoperative hospital stay
      for the six patients with successful laparoscopic procedures was 2.3 days, and
      four patients were dismissed within 48 hours after the procedure. CONCLUSION:
      Laparoscopic adrenalectomy is a safe alternative for the management of
      aldosteronoma of the left adrenal gland.

PMID- 7643638
TI  - Stroke epidemiology in Novosibirsk, Russia: a population-based study.
AB  - OBJECTIVE: To determine first-ever stroke incidence, 30-day case-fatality rates,
      and frequency of various risk factors among patients with stroke in Novosibirsk,
      Russia, during 1992. DESIGN: A population-based study of an administratively
      defined district of Novosibirsk was conducted to identify residents with a first
      ever stroke that occurred between Jan. 1, 1992, and Dec. 31, 1992. MATERIAL AND
      METHODS: For case ascertainment, mortality statistics, death certificates,
      hospital registrations, outpatient clinical data, and all ambulance calls for the
      study area were reviewed. Patients with stroke or suspected stroke were examined
      and interviewed by a cerebrovascular neurologist, and the type of stroke was
      determined. RESULTS: During the 12-month study period, 366 patients with first
      ever stroke were registered. A diagnosis of cerebral infarction or intracerebral
      hemorrhage was confirmed by computed tomography or autopsy in 42% of cases. The
      diagnosis of subarachnoid hemorrhage was established by cerebrospinal fluid
      examination in all 14 cases. The age- and sex-adjusted annual incidence rate for
      stroke was 232 per 100,000. The distribution of incidence cases by diagnostic
      category was as follows: cerebral infarction, 87.7%; intracerebral hemorrhage,
      8.5%; and subarachnoid hemorrhage, 3.8%. The overall 30-day case-fatality rate
      for stroke was 22.4%. Hypertension, angina pectoris, and cigarette smoking were
      the most frequent risk factors in patients with stroke in Novosibirsk.
      CONCLUSION: The incidence rate of first-ever stroke in Novosibirsk, Russia, is
      one of the highest in the world, but the 30-day case-fatality rates are similar
      to those in other populations.

PMID- 7643639
TI  - Human babesiosis.
AB  - OBJECTIVE: To describe a case of human babesiosis and review the literature on
      the disease. MATERIAL AND METHODS: We describe a 62-year-old man with babesiosis,
      outline his clinical course and response to therapy, and discuss the use of the
      polymerase chain reaction for the diagnosis and monitoring of the infection.
      RESULTS: The onset of the disease was insidious, with fatigue, fever, weight
      loss, intermittently discolored urine, and anemia. Computed tomography of the
      abdomen revealed a small, shrunken spleen with an irregular border. With
      treatment, the symptoms gradually resolved. Although peripheral blood smears were
      negative soon after therapy, Babesia microti DNA was detected by polymerase chain
      reaction 53 days after initial examination. CONCLUSION: The development of
      improved methods for diagnosis, including indirect immunofluorescent antibody
      assays and the polymerase chain reaction, provides more sensitive detection of
      the parasitemia associated with babesiosis. Use of these methods may help to
      delineate the complete clinical spectrum of this infection and its geographic
      distribution in the United States.

PMID- 7643640
TI  - Cardiac papillary fibroelastoma: a treatable cause of transient ischemic attack
      and ischemic stroke detected by transesophageal echocardiography.
AB  - Transesophageal echocardiography (TEE) is used frequently in patients with
      cerebrovascular ischemia. On TEE, a typical appearance of a cardiac fibroelastoma
      is that of a pedunculated, mobile mass attached to a leaflet of a valve. Surgical
      excision of the lesion may lead to resolution of the symptoms and prevent further
      cerebrovascular ischemic events; valve replacement is seldom necessary. Herein we
      describe three patients with cerebral or ocular ischemia in whom histologic study
      confirmed a cardiac papillary fibroelastoma after initial detection by TEE.
      Cardiac papillary fibroelastomas should be considered in the differential
      diagnosis of transient ischemic attack and stroke, even in cases of recurrent
      events in the same vascular distribution. Although the use of echocardiography in
      the evaluation of stroke and transient ischemic attack is controversial, TEE must
      be considered in patients in whom the cause of cerebrovascular ischemia is
      unclear after noninvasive neurovascular studies or transthoracic
      echocardiography, even if the patient's cardiac history and the findings on
      physical examination are normal.

PMID- 7643641
TI  - Acquired immunodeficiency syndrome-related Kaposi's sarcoma.
AB  - OBJECTIVE: To describe Kaposi's sarcoma (KS) associated with the acquired
      immunodeficiency syndrome (AIDS). DESIGN: A review of AIDS-related KS (AIDS-KS),
      with its associated epidemiologic and etiologic characteristics, pathogenesis,
      clinical manifestations, histopathologic features, prognosis, and treatment, is
      presented. RESULTS: KS is the most frequent malignant lesion in patients with
      AIDS. The incidence of AIDS-KS is high in homosexual and bisexual men who have
      multiple sexual partners and in children and women with the human
      immunodeficiency virus (HIV) infection. Anal-oral contact is one of the main
      routes of the sexually transmitted agents of AIDS-KS. The major pathogenic
      factors that may possibly induce AIDS-KS are HIV itself or other sexually
      transmitted agents, HIV tat gene, some oncogenes and cytokines such as
      interleukin 6, basic fibroblast growth factor, transforming growth factor-beta,
      oncostatin M, and platelet-derived growth factor. Treatment includes local
      therapy, radiotherapy, systemic chemotherapy, zidovudine, interferon, granulocyte
      macrophage colony-stimulating factor, and other agents. CONCLUSION: KS may be an
      early manifestation of AIDS and the most frequent neoplastic complication of
      AIDS. Growth factors, cytokines, immunosuppression, and interaction with
      infectious agents seem to have a role in the development of this enigmatic
      disorder. Treatment of KS should be individualized. Further investigation of the
      agents and factors of AIDS-KS may help facilitate the treatment and prevention of
      this neoplasm.

PMID- 7643642
TI  - Identification and treatment of complications of myocardial infarction.
AB  - Mechanical complications of acute myocardial infarction include papillary muscle
      rupture with severe mitral regurgitation, ventricular septal rupture with acute
      ventricular septal defect, acute and subacute free-wall rupture, and
      hemodynamically significant right ventricular infarction. Although such
      complications are infrequent, their importance is underscored because of the
      potential ability to correct them with early diagnosis and appropriate treatment.
      The diagnosis necessitates a high degree of suspicion based on clinical clues and
      rapid diagnostic testing. Beside two-dimensional echocardiography, sometimes with
      transesophageal echocardiography, is most commonly used to diagnose or exclude
      these complications. Patients suspected of having a mechanical complication of
      myocardial infarction should be urgently transferred to a medical center
      experienced in the management of these problems. For deteriorating patients
      without identifiable mechanical complications, coronary angiography and
      reperfusion with direct angioplasty should be considered.

PMID- 7643643
TI  - 26-year-old man with HIV infection and abdominal pain.

PMID- 7643644
TI  - Felix Bloch--developer of magnetic resonance imaging.

PMID- 7643645
TI  - Practical functional assessment of elderly persons: a primary-care approach.
AB  - OBJECTIVE: To describe simple, practical measures of physical and psychosocial
      function to detect problems and enhance the care of elderly patients. DESIGN: We
      reviewed pertinent articles and current standard textbooks of geriatrics; the
      most useful findings are summarized, and tools that can be used for functional
      assessment of the geriatric population are presented. RESULTS: Care of elderly
      patients necessitates a comprehensive review of key areas of function. Using only
      clinical judgment, physicians may overlook important clinical deficits common in
      older patients. Because of their length and complexity, many of the standard
      geriatric assessment tools are impractical for use by primary-care physicians.
      Certain simplified or condensed versions--such as the Functional Reach Test and
      the "Get Up and Go" Test--are efficient substitutes. In this article, we describe
      methods for practical identification of functional impairments, assessment of
      cognition and mood, evaluation of hearing and vision, and detection of problems
      with continence, nutrition, and social needs. Instruments for assessment of
      caregiver burden are also outlined. CONCLUSION: Use of the assessment tools
      presented herein can assist primary-care physicians in comprehensive evaluation
      of function in older patients.

PMID- 7643646
TI  - Should chemotherapy replace retroperitoneal lymphadenectomy for clinical stage II
      testicular tumors?

PMID- 7643647
TI  - Surgical gastrostomies versus endoscopic gastrostomies: a tube by any other
      name...

PMID- 7643648
TI  - Method for determining individual neuron size in simultaneous single-unit
      recordings.
AB  - A technique for estimating the size of neurons is based on extracellular
      recordings with paired-electrode sets. Simultaneous single-unit recordings are
      obtained from the dragonfly mesothoracic ganglion. It is assumed that the
      ganglion is a passive electrical environment, where spike amplitudes decrease
      with the inverse of distance squared, and spike angles (widths) increase linearly
      with distance from the cellular source to the recording electrodes. Starting with
      the recorded spike amplitudes and angles for each cell, a numerical algorithm is
      iterated to estimate the true value of the amplitude and angle minus these
      passive electrical distance effects. The resolved amplitude is a direct,
      consistent estimate of the size of each recorded neuron. The results indicate
      that a dichotomy of small and large cells is recorded in roughly a 2:1 ratio. The
      dichotomy of cell sizes is consistent with the available histological data,
      although a larger ratio of small to large cells (approximately 10:1) would be
      expected. Thus, a sampling bias for large cells is apparent, which may be
      reflective of the larger soma/proximal geometries of such cells. As the technique
      determines the size of each individual neuron, such biases are eliminated from
      population studies of the neural tissue. Furthermore, knowledge about the size of
      each individual neuron permits more detailed analyses of the interactions and
      contributions of single cells within a network of cells based upon size.

PMID- 7643649
TI  - Regurgitant heart valve flow from 2-D proximal velocity field: continued search
      for the ideal method.
AB  - It has been suggested that flow through a leaking heart valve can be determined
      by studying the proximal velocity field. Normally, only the centre-line velocity
      is studied as a potential method. The aim of the study is to improve this method
      by using information from the entire reconstructed proximal velocity field. Four
      methods are compared: use of the centre-line velocity; use of velocities at three
      different angles; integration of velocities over a hemisphere; and integration of
      velocities over an estimated hemi-elliptical isovelocity line. Measurements are
      performed in a hydraulic model with 4, 6 and 8 mm circular orifices, and these
      are compared with those from computer simulation. From the results presented in
      the study, it is suggested that the velocities should be integrated over a
      hemisphere within a best zone. This zone is dependent on the instrument settings,
      but in this case it is positioned 1.2-1.4 orifice diameters from the orifice
      inlet, with an angle of up to +/- 45 degrees from the centre axis, and contains
      velocities in the range 0.15-0.45 ms-1.

PMID- 7643650
TI  - Design and application of sensor for recording sounds over human eye and nose.
AB  - The recording of sounds over the orbit of the eye has been found to be useful in
      the detection of intracranial aneurysms. A hydrophone for auscultation over the
      eye has been developed and is tested under controlled conditions. The tests
      consist of measurement over the eyes in three healthy volunteers at rest, during
      voluntary breathing, during eyeball movements and during sustained orbicular
      muscular contractions. Furthermore, measurements are performed at the side of the
      nose. Major features of the hydrophonic transducer are high sensitivity to
      physiological sounds and a high degree of insensitivity to environmental sounds
      propagated through the air. It can be concluded that the hydrophone may be useful
      for the early detection of intracranial aneurysms and also for apnoea detection.

PMID- 7643651
TI  - Implantable data logging system for heart rate and body temperature: its
      application to the estimation of field metabolic rates in Antarctic predators.
AB  - The metabolic rate of free-ranging animals is difficult to measure, but of great
      importance in understanding the interactions of a species with its environment.
      Heart rate can, if correctly validated and calibrated, give an estimate of
      metabolic rate, with both a fine time resolution and over long periods. The
      telemetry of heart rate is well documented, but is not appropriate over long
      ranges (possibly several thousands of kilometres) or for diving species. An
      implantable data logger has therefore been developed for the long term recording
      of heart rate and body temperature. The logger is built using hybrid and ASIC
      construction techniques, weighs 20 g and measures 55 x 24 x 6 mm. The device is
      programmable, and its solid-state memory holds over 70 days of data if, for
      example, heart rate is counted and stored every minute. Current consumption is
      155 microA while logging, 50 microA during a programmable initial delay period,
      and less than 1 microA when the logger closes down after filling its memory.
      These loggers have been deployed for two field seasons in gentoo penguins, black
      browed albatross and fur seals.

PMID- 7643652
TI  - Fibre-optical sensor based on fluorescent indicator for monitoring physiological
      pH values.
AB  - A fibre-optical sensor has been developed based on the fluorescent indicator 8
      hydroxyl-1,3,6-pyrene trisulphonic acid trisodium salt (HOPSA) for monitoring
      physiological pH values. Dowex-1 strongly basic anion exchange resin is used as
      the medium to immobilise the indicator on the end of an optical fibre.
      Polyurethane is coated on the sensor as the permeable membrane for H+. The
      properties of HOPSA in solution, as well as when immobilised on the sensor, are
      studied and found to have the potential for monitoring physiological pH values.

PMID- 7643653
TI  - In vivo assessment of catheter-tip PO2 sensor: sampling lumen fabrication.
AB  - Fabrication of the sampling lumen of an intra-arterial PO2 sensor is performed in
      standard catheters mechanically or by laser. Clinical evaluation is performed
      with respect to catheter insertion, complications, accuracy of oxygen sensor data
      and fibrin deposition on the catheter surface. The success rate for catheter
      insertion is 57% for 138 standard and 50% for 74 laser-cut catheters studied. The
      proportion of catheter failures (blocked or non-reading) is 14% in laser-cut
      compared with 30% in standard. These differences are not statistically
      significant at the 5% level. There is no clinically significant difference in
      sensor accuracy, with 37.5% of results within +/- 0.05 kPa and 80% within +/- 2.0
      kPa of simultaneous blood gas values. Drift is within +/- 0.3 kPa h-1 for 78% of
      monitoring time. Significant errors of recalibration occur in 6% of calibrations.
      Scanning electron micrographs demonstrate a much smaller sampling lumen in the
      laser-cut group, but no reduction in fibrin deposition at the site of the
      sampling hole. The low success rate for catheter insertion is a problem because
      of cost implications. The accuracy of the system is usually sufficient for
      clinical purposes, provided the calibration is checked every 4 h.

PMID- 7643654
TI  - Application of computer graphics for assessment of spinal deformities.
AB  - A graphical portrayal system to assess spinal deformities is described. The
      system is based on software to display and manipulate three-dimensional images of
      the spine and trunk surface. Qualitative measurements of internal spinal
      alignment and trunk appearance are provided. The graphics display is developed
      using graPHIGS routines in conjunction with the C programming language and the
      UNIX operating system. This software provides clinicians with a computer-aided
      measurement tool that rapidly conveys clear and concise information about the
      deformities associated with abnormal spinal curvatures.

PMID- 7643655
TI  - Role of equalisation mammography of dense breasts.
AB  - Parenchymal patterns characteristic of dense breasts are known to degrade the
      mammographic detection of small breast cancers and microcalcifications. This
      arises from large variations in exposure of the film, resulting in reduced image
      contrast over areas of suboptimal exposure. Based on sensitometric measurements
      of mammograms from a typical patient population, it is shown that over 60% of a
      typical mammogram in Wolfe's DY classification was found to be exposed
      suboptimally, suggesting a significant margin for improving mammography for these
      patients. In order to address this problem, a prototype mammographic version of
      scanning equalisation radiography (MSER) has been developed, which delivers a
      patient-specific spatially non-uniform distribution of breast exposure, adjusted
      to maintain optimal film exposure and contrast over the entire mammogram.
      Anthropomorphic phantom MSER images show a marked improvement in subjective image
      quality relative to conventional mammograms, while exhibiting a similar radiation
      risk. The detection of small microcalcifications and fibrils over clinically
      significant breast densities is found to be improved by factors eight and four,
      respectively. Such a system may be clinically practical through the use of
      multiple-beam equalisation methods with available X-ray tube technology.

PMID- 7643656
TI  - Computer-aided detection of clustered microcalcifications on digital mammograms.
AB  - A computer-aided diagnosis scheme to assist radiologists in detecting clustered
      microcalcifications from mammograms is being developed. Starting with a digital
      mammogram, the scheme consists of three steps. First, the image is filtered so
      that the signal-to-noise ratio of microcalcifications is increased by suppression
      of the normal background structure of the breast. Secondly, potential
      microcalcifications are extracted from the filtered image with a series of three
      different techniques: a global thresholding based on the grey-level histogram of
      the full filtered image, an erosion operator for eliminating very small signals,
      and a local adaptive grey-level thresholding. Thirdly, some false-positive
      signals are eliminated by means of a texture analysis technique, and a non-linear
      clustering algorithm is then used for grouping the remaining signals. With this
      method, the scheme can detect approximately 85% of true clusters, with an average
      of two false clusters detected per image.

PMID- 7643657
TI  - Conoidal dipole model of electrical field produced by the human stomach.
AB  - Spontaneous depolarisation and repolarisation due to ionic exchange are the main
      properties of smooth muscle cells in the human stomach. This change in the
      distribution of electrical charge results in the creation of an electric field.
      The field manifests itself as a potential difference (biovoltage), recorded both
      in vitro and in vivo and known as gastric electrical activity (GEA). The aim of
      the paper is to describe a computer model of this electric phenomenon,
      considering all anatomical and electrophysiological particularities of the
      stomach, and to simulate real in vivo experiments with a computer. In the
      proposed model, the depolarised smooth muscle cells are represented as organised
      electrical dipoles distributed with known density in an annular band that moves
      distally with increasing velocity. Computer simulations of in vivo experiments
      using this model not only give the waveform, duration, amplitude and frequency of
      GEA, but they also represent the phase lag between different channels, the
      difference in propagation velocity along greater and lesser curvatures, and the
      electric coupling between different parts of the stomach. The effects of changed
      electrode configuration, surface area and distance from the stomach are
      described. Mathematical modelling is done in spherical co-ordinates, and the
      simulations are performed in a specially designed user-friendly IBM PC
      environment. Some of the unsolved problems in cutaneous electrogastrography are
      also discussed.

PMID- 7643658
TI  - Prediction of reactive hyperaemia in vascular pathologies using elastic porous
      tube model.
AB  - A mathematical model of reactive hyperaemia has been developed, in which the limb
      vascular system is represented by an elastic porous tube, with flow in the tube
      equivalent to blood flow in the arteries and large arterioles. Flow through the
      porous walls represents flow into the small arterioles, which respond actively by
      contracting as pressure throughout the system rises following occlusion release.
      A variety of vascular pathologies have been simulated; the effect of venous
      packing of the limb is to reduce the transient peak flow from normal, owing to a
      reduction in the pressure gradient. Occlusive disease of the femoral artery and
      lower arterial vessels reduces the magnitude and extends the duration of
      hyperaemic flow, due to a reduced pressure gradient and increased resistance.
      Small vessel disease reduces the hyperaemic flow, principally due to a reduction
      in the initial dilation of the vessels. Venous disease does not affect the
      initial arterial flow following occlusion release but reduces the equilibrium
      flow. The venous outflow increases in response to an increase in the arterio
      venous pressure gradient.

PMID- 7643660
TI  - Buckling of elastic tubes: study of highly compliant device.

PMID- 7643659
TI  - Toolkit for lung sound analysis.

PMID- 7643661
TI  - Practical factors in neonatal lung imaging using electrical impedance tomography.

PMID- 7643662
TI  - Three-dimensional kinematic angle measurement system for non-jointed rigid axes.

PMID- 7643663
TI  - Stereophotogrammetric-controlled pointing device for neurosurgical use.

PMID- 7643664
TI  - Two-dimensional vibrating platform in nm range.

PMID- 7643665
TI  - Software system for automatic parameter logging on Philips SL20 linear
      accelerator.

PMID- 7643666
TI  - OPTONET: neural network for visual field diagnosis.

PMID- 7643667
TI  - Cerebral and muscle oxygen saturation measurement by frequency-domain near-infra
      red spectrometer.
AB  - Tissue oxygen saturation quantification was obtained using a frequency-domain
      multi-source method based on two wavelength light-emitting diodes. Brain
      saturation was 60.3 +/- 1.1% (n = 12). Brachioradial muscle saturation declined
      during forearm ischaemia and maximal voluntary contraction from 73.7 +/- 1.8 and
      74.7 +/- 1.8% at rest to 44.2 +/- 3.3 and 61.4 +/- 2.9%, respectively.

PMID- 7643668
TI  - Open flow microperfusion: approach to in vivo glucose monitoring.
AB  - A slow flow of liquid over the working tip of a classical glucose needle
      electrode allows a significant reduction in surface fouling with minimal sample
      dilution. The fluid flow technique enables relatively drift-free in vivo
      operation for up to four hours (electrode responses in vitro following
      explanation of the device after a 4 h monitoring period are within +/- 5% of
      original values), exhibits a close correlation with blood glucose levels and is
      unique in requiring no in vivo calibration.

PMID- 7643669
TI  - Biomagnetic functional localisation: iterative approach to estimation of
      electrical sources within the human heart from the magnetocardiogram.

PMID- 7643670
TI  - Mr Troutbeck as the surgeon's friend: the coroner and the doctors--an Edwardian
      comedy.

PMID- 7643671
TI  - Pancreatic organotherapy for diabetes, 1889-1921.

PMID- 7643672
TI  - Questions of competence: the midwife debate in The Netherlands in the early
      twentieth century.

PMID- 7643673
TI  - Socialist proposals for health reform in inter-war Britain: the case of
      Somerville Hastings.

PMID- 7643675
TI  - The market for medicine. Essay review.

PMID- 7643674
TI  - The archive of the Health Visitors' Association in the Contemporary Medical
      Archives Centre.

PMID- 7643676
TI  - Medicine and empire. Essay review.

PMID- 7643677
TI  - Sensibility reconsidered. Essay review.

PMID- 7643678
TI  - [The chairman of the SLMK 50 years after Hiroshima: the turn of the century is a
      historical chance to abolish nuclear weapons].

PMID- 7643679
TI  - [The athletic world championship in Gothenburg].

PMID- 7643680
TI  - [Organization of health care services must be further developed. Variety means
      vitality and development].

PMID- 7643681
TI  - [Professional competence is as important as engagement and humility].

PMID- 7643682
TI  - [Premature distribution of research grants!].

PMID- 7643684
TI  - [Physicians connected to insurance companies must have responsibilities].

PMID- 7643683
TI  - [It is important that the medical societies condemn capital punishment].

PMID- 7643685
TI  - [Sick health care services?].

PMID- 7643686
TI  - [Meta-analyses--the alchemy of statistics?].

PMID- 7643688
TI  - [Vascular surgeons make comparison with the USA. Low level of Swedish control
      over implants].

PMID- 7643687
TI  - [Sudden cardiac death may be caused by malnutrition. High carbohydrate diet may
      cause energy imbalance in athletes].

PMID- 7643689
TI  - [Consequences of the new rules on investigation of fatal cases: possibility of
      risk that unnatural deaths will not be discovered].

PMID- 7643691
TI  - [Social differences are underestimated in statistics. Importance of developing
      new methods of measurement!].

PMID- 7643690
TI  - [Hope of a vaccine against neonatal GBS infection].

PMID- 7643692
TI  - [Seemingly banal trauma with severe consequence. Observations on high-pressure
      injection injuries].

PMID- 7643694
TI  - [85 per cent protection with vaccines against whooping cough. Three acellular
      multicomponent vaccines are best].

PMID- 7643693
TI  - [The teacher as coach. May we learn from sports?].

PMID- 7643695
TI  - [The final spurt prior to general vaccination against whooping cough. More than
      100 000 children participated in trials of 3 different vaccines].

PMID- 7643696
TI  - [Ships over the whole world may receive health care via radio from Gothenburg].

PMID- 7643697
TI  - [Private health insurance can improve health care].

PMID- 7643698
TI  - [Unethical private practice in Sweden?].

PMID- 7643699
TI  - [Quality assurance of child health services is required at different levels of
      care].

PMID- 7643700
TI  - [New antidepressive agents widen the indications. Affective disorders in a new
      perspective].

PMID- 7643701
TI  - [Antibiotic resistance threatens public health. Good chances in Sweden to stop
      the invasion].

PMID- 7643702
TI  - [Environmetal factors at home, in schools and in workplaces. Ways to decrease
      exposure to allergens].

PMID- 7643703
TI  - [Antibiotics against reactive arthritis? A therapy with only a marginal effect on
      joint symptoms].

PMID- 7643704
TI  - [Splenic rupture in subclinical mononucleosis. Consider conservative therapy!].

PMID- 7643705
TI  - [New technology in medicine and education. It is possible to simulate everything
      in "virtual reality"].

PMID- 7643706
TI  - [Surprising conclusions on test-tube fertilization. The risks for children are
      underestimated by the ethical committees].

PMID- 7643707
TI  - [New ways in the treatment of severe genetic dermatoses. Increasing hope with the
      progress in molecular biology].

PMID- 7643708
TI  - [Viper bite--clinical aspects and treatment].

PMID- 7643709
TI  - [Are X-ray examinations causing cancer? A debate on low-dosage irradiation 100
      years after Rontgen].

PMID- 7643710
TI  - [The freedom of choice threatens to kill sectorized psychiatry. An unhappy
      political game played for the galleries].

PMID- 7643712
TI  - [Adverse effects of drugs in 1994. New unexpected connections were proved].

PMID- 7643711
TI  - [Syndromes with severe insulin resistance. Rare conditions but their
      identification is important].

PMID- 7643713
TI  - Nitroxidergic vasodilator nerve in the canine nasal mucosa.
AB  - The canine nasal mucosa was studied by in vitro bioassay. Non-adrenergic, non
      cholinergic (NANC) vasodilator response to transmural electrical stimulation was
      observed in the presence of guanethidine and atropine. This vasodilator response
      was abolished by NG-nitro-L-arginine (L-NA) which is an inhibitor of nitric oxide
      (NO) formation but not by NG-nitro-D-arginine. The inhibitory effect of L-NA was
      partially reversed by treatment with L-arginine but not with D-arginine. The
      vasodilator response was significantly suppressed by tetrodotoxin. The present
      results indicate that NO may mediate neurogenic vasodilation in the canine nasal
      mucosa.

PMID- 7643714
TI  - Effect of four potassium channel agonists on bupivacaine-induced toxicity in
      mice.
AB  - The influence of four potassium channel agonists i.e. diazoxide (D),
      levcromakalim (L), nicorandil (N) and pinacidil (P) on bupivacaine-induced acute
      toxicity was evaluated by measuring the convulsant activity, the time of latency
      to convulse and the mortality rate. Four different dosages (i.e. 0.1, 1, 10 and
      100 mg/kg/i.p. for D, N and P and 0.01, 0.1, 1 and 5 mg/kg/i.p. for L) were
      injected to a total of 200 male NMRI adult mice: 16 groups of 10 mice each were
      previously treated by a single i.p. dose of each potassium channel agonist while
      controls (n = 40) received saline injection. Thus, 15 minutes later, all groups
      were injected with a 50 mg/kg/i.p. single dose of bupivacaine. The convulsant
      activity of bupivacaine was significantly modified by only high doses of L in a
      dose-dependent manner. Compared to the controls, the period of latency was
      significantly increased for most of the doses of P, N, D and L in a dose
      dependent manner for L and P. The anesthetic-induced mortality (47.5% for
      controls) was not significantly modified by D, but decreased by N and increased
      by high doses of L and P which is probably related to a delayed mortality.

PMID- 7643715
TI  - Localization to chromosome 10 of a locus influencing morphine analgesia in
      crosses derived from C57BL/6 and DBA/2 strains.
AB  - A quantitative trait locus (QTL) was detected and mapped to proximal chromosome
      10 near the markers Mpmv5 and D10Mit51 with a strong influence on morphine
      induced analgesia in the BXD recombinant inbred (RI) strains and in an F2 cross
      (B6D2F2) between the BXD progenitor strains, C57BL/6 and DBA/2. A LOD score of
      3.9 (p < .00002) was seen for analgesia using the hot plate assay. Naloxone Bmax
      was also associated with this chromosome region in BXD RI mice. The mu opioid
      receptor gene (Oprm) has recently been mapped to this same chromosome region. The
      observation that several morphine-related traits and naloxone Bmax appear to be
      partly determined by this presumed single locus is consistent with the hypothesis
      that the mu opioid receptor gene, or one of its modulators, is the basis for the
      QTL.

PMID- 7643716
TI  - Effects of doxorubicin on cardiomyocytes with reduced level of superoxide
      dismutase.
AB  - Our previous studies have shown that isolated adult rat cardiomyocytes with
      normal and reduced Cu/Zn SOD activities are equally susceptible to
      extracellularly generated oxidants (hydrogen peroxide, glucose oxidase/glucose
      and xanthine oxidase/xanthine systems). In the present study we exposed myocytes
      with reduced SOD activity to doxorubicin (adriamycin). Cardiotoxicity of
      doxorubicin has been attributed to the production of superoxide anion inside the
      cell. Cardiomyocytes with reduced SOD activity, but normal ATP content and
      viability, were obtained by the treatment of isolated cells with
      diethyldithiocarbamate (DDC). DDC-treated myocytes were significantly less
      resistant to doxorubicin than controls. Doxorubicin-stimulated superoxide anion
      formation, measured by the rate of SOD-inhibitable acetylated cytochrome C
      reduction, was significantly higher in the cytosolic fraction of DDC-treated
      cells compared to controls. These results indicate that for isolated cardiac
      myocytes an essential part of cytotoxicity of doxorubicin can be explained by the
      formation of superoxide anion and that the level of intracellular SOD activity
      should be considered as a significant factor for cell protection.

PMID- 7643717
TI  - Antagonists of the NMDA receptor-channel complex and motor coordination.
AB  - Many structurally different, centrally active antagonists of the NMDA receptor
      channel complex induce phencyclidine-like side effects in mammals which include
      head weaving, body rolling, sniffing and disturbances of motor coordination. The
      ability of these compounds to cause disturbances of motor coordination correlates
      directly with their ability to antagonize the NMDA receptor-channel complex in
      vivo. Although noncompetitive antagonists increase motility in rodents, whereas
      competitive antagonists do not, both classes of compounds appear to induce
      schizophrenia-like psychosis in human beings, and cause similar changes in a
      variety of different biogenic amine neurotransmitter systems in the limbic and
      motoric areas of the brain. The complex spectrum of behavioural effects observed
      after the administration of antagonists of the NMDA receptor-channel complex
      probably reflects the intricate nature of the interaction with positive and
      negative feedback loops of the motor circuit. Recent research indicates that the
      site of integration of this interaction could be the striatal medium spiny
      GABAergic neuron.

PMID- 7643719
TI  - Dimethyl sulfoxide inhibits renal Na(+)-K(+)-ATPase at a site different from
      ouabain and atrial peptides.
AB  - The present investigation was designed to determine 1) if dimethyl sulfoxide
      (DMSO) inhibits renal cortical and medullary Na(+)-K(+)-ATPase at the ouabain
      binding site and 2) if this inhibition of Na(+)-K(+)-ATPase by. DMSO involves
      atrial natriuretic peptides or prostaglandins. DMSO (10%) inhibited renal
      cortical and medullary Na(+)-K(+)-ATPase 31% and 29.5%, respectively. Ouabain
      (0.5 mM) inhibited renal cortical and medullary Na(+)-K(+)-ATPase 32% and 35%,
      respectively. When DMSO and ouabain were added together the inhibition of renal
      cortical and medullary Na(+)-K(+)-ATPase was 55% and 59%, respectively. Atrial
      natriuretic peptides consisting of amino acids 1-30 (i.e., long acting
      natriuretic peptide), 31-67 (vessel dilator), 79-98 (kaliuretic peptide) and 99
      126 (atrial natriuretic factor, ANF) of the 126 amino acid ANF prohormone
      inhibited renal cortical Na(+)-K(+)-ATPase 27.5%, 20%, 37.5% and 0% at a 10(-11)M
      concentration. The addition of DMSO caused a doubling (P < 0.05) of this
      inhibition. Likewise, these same atrial peptides inhibited renal medullary Na(+)
      K(+)-ATPase 27.8%, 19.2%, 39.5%, and 0% with DMSO doubling (P < 0.05) their Na(+)
      K(+)-ATPase inhibition. There was not any additive effect of any of the atrial
      peptides with ouabain. Naproxen, a prostaglandin inhibitor, completely blocked
      atrial peptides and ouabain's inhibition of Na(+)-K(+)-ATPase but not DMSO's.
      Each of the atrial peptides except ANF increased prostaglandin E2 synthesis while
      DMSO did not increase prostaglandin E2 synthesis. This investigation suggests
      that DMSO has its inhibiting effect at a site different from the ouabain binding
      site on renal Na(+)-K(+)-ATPase since it has an additive effect with ouabain in
      inhibiting Na(+)-K(+)-ATPase while the atrial peptides appear to have their
      effect at the ouabain binding site. As opposed to the atrial peptides, DMSO's
      mechanism of inhibiting Na(+)-K(+)-ATPase does not appear to involve
      prostaglandin E2.

PMID- 7643720
TI  - Thromboxane A2 and platelet-activating factor decrease in the platelet-mesangial
      cell interactions.
AB  - To analyze the metabolisms of platelet-activating factor (PAF) and Thromboxane A2
      (TxA2) when platelets and mesangial cells (MC) interact, immunoreactive
      thromboxane B2 (TxB2) and PAF were measured after incubation of cultured rat MC
      with platelets (P) and with platelet supernatants (PS). In both cases, TxB2
      significantly decreased with respect to the P synthesis and to the PS content,
      suggesting an increased degradation of this metabolite or even the existence of a
      specific effect of MC upon platelet TxB2. When immunoreactive PAF was measured,
      results were comparable to those observed for TxB2. Moreover, when intrinsic
      mesangial cell synthesis of PAF was assessed by analyzing the [3H]-acetate
      incorporation by prelabeled MC in the HPLC fraction coeluting with cold PAF
      standards, it was possible to demonstrate that P or PS did not modify PAF
      synthesis in these cells. In summary, present results support the existence of a
      specific effect of mesangial cells upon platelet TxA2 and PAF.

PMID- 7643718
TI  - Protection by pyruvate against inhibition of Na+, K(+)-ATPase by a free radical
      generating system containing t-butylhydroperoxide.
AB  - Global tissue damage due to oxygen-derived free radicals has been implicated in
      several pathological processes including exposure to ionizing radiation, and
      postischemic reperfusion of the heart or kidney. Recently pyruvate, a
      hydroperoxide scavenger, has been shown to protect against functional damage
      during postischemic reperfusion of the heart and in acute renal failure. In the
      present study, pyruvate was found to protect against inactivation of partially
      purified guinea pig renal and rat cardiac Na+,K(+)-ATPase which occurred when
      microsomal membranes were assayed for 1 hr at 37 degrees C (pH 7.5) in the
      presence of a free radical generating system (FRGS) containing 0.3 mM t
      butylhydroperoxide and horseradish peroxidase. The presence of the FRG system
      inhibited the guinea pig renal Na+,K(+)-ATPase activity by 48.2 +/- 4.8% (N = 10,
      P < .05) and the presence of 0.2 to 20 mM pyruvate partially protected the
      Na+,K(+)-ATPase. At 5 mM pyruvate Na+,K(+)-ATPase was inhibited by only 18.8 +/-
      2.5% (N = 10, P < .05) but increasing the pyruvate concentration gave no further
      protection. Equimolar concentrations of glucose, mannitol or lactate were without
      effect. The protection appeared to require an alpha-keto acid since alpha- but
      not beta-ketoglutarate was also effective and the mechanism is most probably the
      scavenging of t-BHO2. The results of the present study therefore support the
      hypothesis that, if free radical damage to native Na+,K(+)-ATPase does contribute
      to global tissue injury in certain pathological processes, pyruvate, in addition
      to being a powerful metabolic effector of recovery, may also protect against
      oxidative damage.

PMID- 7643721
TI  - Reperfusion-induced arrhythmias and lethality are reduced by a 2KDa heparin
      fragment.
AB  - The influence of a low molecular weight heparin (Oligo-H, m.w. 2KDa) on
      ventricular arrhythmias and lethality induced by heart reperfusion following a 5
      min coronary occlusion was studied in anesthetized rats. Both intravenous (i.v.)
      and subcutaneous (s.c.) injection of the compound dose- and time-dependently
      prevented the reperfusion syndrome: in all saline-pretreated animals post
      ischemic reperfusion induced ventricular tachycardia (VT), which degenerated into
      ventricular fibrillation (VF) in 25 out of 30 rats, with a mortality rate of 73%;
      on the other hand, in rats i.v. or s.c. pretreated with Oligo-H (20 mg/kg, 30 and
      90 min, respectively, before coronary occlusion), VT occurred in 4 out of 10-11
      animals and degenerated into VF in 2-3 out of 10-11 animals, with a mortality
      rate of 18-20%. Even more effective was a low molecular weight dermatan sulfate
      (Oligo-DS, m.w. 2.1KDa). In rats treated with lidocaine, used as reference
      compound, at the dose of 5 mg/kg i.v. 10 min before coronary occlusion, VT
      occurred in 2 out of 10 animals and degenerated into VF in 1 out of 10 animals,
      with a mortality rate of 10%. It is concluded that low molecular weight
      glycosaminoglycans significantly reduce the consequences of heart reperfusion.

PMID- 7643722
TI  - Differential effect of ursodeoxycholate and its taurine conjugate on biliary
      transport maximum of bilirubin in the rat.
AB  - The effects of ursodeoxycholate and its taurine conjugate on biliary Tm of
      bilirubin were evaluated in rats. Ursodeoxycholate was administered at four
      different doses (4, 8, 12 or 16 mumol per 100 g body wt i.v., followed by an i.v.
      infusion of 0.3, 0.6, 0.9 or 1.2 mumol/min per 100 g body wt, respectively),
      whereas tauroursodeoxycholate was administered only at the maximal dose. A dose
      dependent diminution of bilirubin Tm was observed during ursodeoxycholate
      administration, which ranged from no effect at the lowest dose to a virtual
      excretory blockage at the highest dose. This was associated with an increase in
      bilirubin concentrations in both plasma and liver as well as in the fractional
      amount of conjugated pigment in both sites, suggesting an impairment of bilirubin
      transfer at the canalicular level. Incomplete taurine conjugation of
      ursodeoxycholate well correlated with these effects. Unlike ursodeoxycholate,
      tauroursodeoxycholate had no inhibitory effect on bilirubin Tm, although a slight
      inhibition of bilirubin uptake and bilirubin conjugation became apparent. Taken
      together, these results suggest that ursodeoxycholate interferes with the
      hepatobiliary transport of bilirubin by impairing its transfer at the canalicular
      level and that incomplete taurine conjugation appears to be a key factor
      determining this effect.

PMID- 7643723
TI  - Antithrombotic nipecotamide increases cyclic AMP levels and inhibits protein
      phosphorylation in human platelets.
AB  - alpha,alpha'-bis[3-(N,N-diethylcarbamoyl)piperidino]-p-xylene dihydrobromide (A
      1), a typical antithrombotic nipecotamide, elevated the levels of cyclic
      adenosine monophosphate (cAMP) in human platelets in vitro, without inhibiting
      cAMP-phosphodiesterase (PDE). The compound elevated the basal cAMP levels,
      enhanced the prostaglandin (PG)E1-stimulated platelet adenylyl cyclase (AC)
      activity, and prevented the ADP-induced decline of the latter. Collagen-induced
      phosphorylation of 20 and 47 kDa proteins was inhibited by IC50 and 0.5 x IC50
      concentrations. In light of the known actions of A-1, it is suggested that
      stimulation of AC and inhibition of agonist-induced rise in cytosolic ionized
      calcium ([Ca2+]i) may constitute an aspect of its mechanism of action.

PMID- 7643724
TI  - Effects of deferoxamine and a diet deficient in vitamin E on isoelectric
      electroencephalographic responses associated with ischemia by the four vessel
      occlusion method.
AB  - This study reports the effects of subchronic administration of the iron chelator
      deferoxamine (4.2 mg/day by osmotic minipump for 6 days) and a diet deficient in
      Vitamin E (15% RDA for 60 days) on the isoelectric electroencephalographic
      responses associated with 15 minutes of global transient cerebral ischemia in
      rats. Brain levels of thiobarbiturate-reacting substance (TBARS), a measure of
      lipid peroxidation, were lower in deferoxamine-treated animals and higher in
      Vitamin E deficit animals suggesting the treatments altered free radical activity
      at the time of ischemia. During ischemia, all test animals were observed to lose
      the righting reflex and enter a quiescent state. Fifty percent of the animals in
      two control groups (N = 15 per group) demonstrated an isoelectric
      electroencephalographic pattern (defined as 10% or less of pre-ischemia total EEG
      power) with a mean onset of 5.44 minutes. One third of the animals treated with
      deferoxamine (N = 15) experienced an isoelectric encephalogram with a mean onset
      of 8.6 minutes and 73% of the Vitamin E-deficient group (N = 15) experienced an
      isoelectric EEG with a mean onset of 3.43 minutes. Following reperfusion, EEG
      patterns returned to power levels within 20% of pre-ischemia levels in all
      animals. Control animals obtained this EEG power level within 1.34 minutes,
      deferoxamine-treated animals within 1.25 minutes and animals provided a diet
      deficient in Vitamin E within 5.03 minutes. Compared to mean total EEG power
      prior to the onset of ischemia, mean total EEG power five days after reperfusion
      was reduced 14% in the control groups and 59% in the Vitamin E-deficient group
      and increased 123% in the deferoxamine group. Results are discussed in relation
      to the possible involvement of free radicals in the ischemic and postischemic
      process.

PMID- 7643725
TI  - Identification of rat urinary kinin as bradykinin.
AB  - Bradykinin (BK)-like activity, which was detected by BK-enzyme-immunoassay, was
      purified from 80 ml of ureter urine of Sprague-Dawley rats by Sephadex G 25
      chromatography, FPLC, and reversed phase HPLC. The purified kinin fraction showed
      the same retention time as authentic BK on HPLC and produced contraction of
      isolated rat uterus, the contraction being suppressed by a B2-antagonist Hoe140.
      There was no other kinin detected on the HPLC at the corresponding retention time
      to kallidin, arginyl-BK or T-kinin. The peptide showed an amino acid sequence
      identical to that of BK by amino acid sequence analysis.

PMID- 7643726
TI  - Richard Ferri elected president of National AIDS Nursing Association.

PMID- 7643727
TI  - New HIV/AIDS treatment information service.

PMID- 7643729
TI  - [Comments relating to the psychosexual characteristics of the male transsexual. A
      clinical study].
AB  - In this paper the authors analyse transexualism from a psychopathological,
      nosographic and clinical point of view. The re-examine the theories on the
      subjects elaborated by a number of authors and describe the clinical
      characteristics of the syndrome, paying special attention to problems relating to
      differential diagnosis. Moreover, they present the results ofa study carried out
      in a personal series of cases. The sample studied included 11 male transsexual
      subjects. The latter were evaluated through psychiatric interview and a
      questionnaire aimed at obtaining information on the following topics: the
      subjects' social and affective relations; their childhood experience; their
      perception and acceptance of themselves; the meaning, characteristics,
      localisation and experience of sexual pleasure. The results are discussed and
      compared with those of national and international literature on this subjects.

PMID- 7643728
TI  - [Clinical course and social outcome in schizophrenia. Results from a
      retrospective study].
AB  - OBJECTIVE: The aim of the present study is to investigate the possible clinical
      and symptomatological determinants of social outcome in schizophrenic patients.
      METHOD: 40 schizophrenic patients (DSMIII-R), 21 males and 19 females, mean age 4
      +/- 5 years, have been evaluated in the present retrospective study. All of them
      had first undergone psychiatric hospitalization between 1978 and 1981. The
      following data have been collected: socio-anagraphic features and course of the
      illness (AMDP), contacts with community health centre and pharmacological
      compliance. Social disability has been investigated by means of a semi-structured
      interview developed from the "Disability Assessment Schedule" named "Accertamento
      Disabilita e Carico Familiare" (ADC), which has been administered to the main
      carer, usually a cohabitant relative. Presence and level of social support have
      also been evaluated. One Way Analysis of Variance (ANOVA), "t" test with
      Bonferroni correction and Pearson Correlation test have been used for data
      analysis. RESULTS: Patients with less severe social disability (lower scores at
      ADC) were mainly those with recurrent course of illness without residual symptoms
      or remitted ones (p = 0.0001), better pharmacological compliance (p = 0.004),
      more frequent and regular contacts with community health centres (p = 0.0001) and
      better social support (p = 0.01). On the contrary, score at ADC resulted
      positively correlated with number of hospitalizations (r = 0.57, p = 0.01),
      number of compulsory admission (r = 0.32, p = 0.01) and length of illness (r =
      0.40, p = 0.01). CONCLUSIONS: Although in our study the influence of severity of
      illness on social disability has been confirmed, suggestive evidence about
      importance of other factors, such as compliance or social support, may be drawn.

PMID- 7643730
TI  - [The concept of metamorphosis in psychopathology].
AB  - The authors take into account the psychopathological issue of "metamorphosis" (or
      transformation of the Self) firstly with the observation of some clinical cases.
      The psychopathological problem is set as a disorder of the s.c. "awareness of the
      Self" and considered in the light of a close relationship with the subjective
      body experience. The clinical discussion on the metamorphosis problem is
      developed taking also into account the data coming from the anthropological
      research.

PMID- 7643731
TI  - [Classification systems for the clinical approach to pervasive developmental
      disorders].
AB  - This paper compares four systems for the classification of pervasive
      developmental disorders: DSM-III-R, ICD-10, the French classification of mental
      disorders in children and adolescents and Manzano and Palacio-Espasa's
      operational classification. Five children were examined according to a protocol
      which included clinical and instrumental examination, the BSE scale, a
      development scale and a psychodynamic observation recorded by video camera. A
      detailed discussion of the diagnosis of one of the cases is reported as an
      example, while a synthetic description is given of the other four. The comparison
      highlights the characteristics of the four systems considered. The differing
      theoretical premises which inspire them mean that it is important to use all four
      in the clinical investigation of each case: DSM-III-R and ICD-10 can be used for
      the initial screening, whilst the other two can be used to classify more
      specifically all the forms of infantile psychosis.

PMID- 7643733
TI  - [ Theater art as alternative psychotherapeutic treatment in an alcoholic patient.
      Report of a clinical care].
AB  - The authors in this paper suggest the application of an alternative
      psychotherapeutic strategy (Theatrical Art) in a no responder borderline patient.
      The aims of treatment (to wean completely the patient, to strengthen his Ego, to
      enter him into a group with different learning), that are the preliminary to live
      health life for the patient after discharge, have been attained.

PMID- 7643732
TI  - [Personality disorders and obsessive-compulsive disorder: critical analysis of
      the literature data and our studies].

PMID- 7643734
TI  - [Sexuality: social and cultural aspects].

PMID- 7643735
TI  - [Traits of personality in hypochondriacal subjects].
AB  - Among the several mental originated clinical syndromes, hypochondria is not still
      well understood and listed. Indeed, hypochondria is often a complicating element
      in other psychopathological pictures; a slight form of hypochondria can appear in
      phobic-obsessing neurosis, and a worse one at the beginning of psychosis. The
      Authors, trying to explain the complex questions about diagnosis and prognosis of
      hypochondria, look for common personality traits in these patients. The research
      instrument was the Adjective Check List (ACL), a psychological test highly
      standardized and diffused, composed of 300 adjectives, or adjectival sentences,
      used to describe a person's attributes. The ACL was given to 65 subjects divided
      into two groups. The first group was made of 15 subjects, 10 women and 5 men,
      ambulatory treated at the Psychiatric Clinic in Trieste for the following
      diagnosis: psychosis (4 persons), depressing syndrome (3 persons), hypochondria
      (6 persons), obsessive neurosis (1 persons), anxiety syndrome (1 person). The
      second group was made of 50 subjects, 28 women and 22 men, diagnosed as
      hypochondriac by their medical officers. The results point out that some
      personality traits rising above the others are suggesting for an apathetical
      patient, not ready to accept himself, easily overcome by everyday life problems.
      These subjects are introverted, intolerant to frustrations, and inclined to take
      refuge in their own imaginary world, not able to self-governing. In the
      considered group the Authors find a moderate tendency to change, and it could be
      interpreted like a good prognostic element for a psychotherapeutic treatment.

PMID- 7643736
TI  - [Possible relationship between childhood malaise and psychiatric disorders in
      adulthood. Preliminary study on an in-patient sample from the psychiatric unit of
      the general hospital in Pavia].
AB  - The authors report the preliminary data of a study which aims to identify the
      variables (socio-demographic, clinical and nosographic) which may be used to
      predict the evolution of psychiatric disorders. A retrospective follow-back study
      was carried out using the medical records and any other documentation available
      from medical and psychological centers in order to identify the evolutionary
      stages of disease and possible pre-disease antecedents. The sample group examined
      was selected from users attending the Diagnosis and Treatment Psychiatric Unit at
      Pavia Hospital who were found to have undergone infantile neuropsychiatric
      outpatient or hospital treatment during childhood. The preliminary phase of the
      study reports the results of the first 42 cases. The predictive value of the
      diagnosis made during childhood emerges from an analysis of the results and
      consequently emphasises the need to orient Infantile Neuropsychiatric structure
      not only towards diagnosis and care but also, towards a more strictly therapeutic
      action.

PMID- 7643737
TI  - [Mental disease between norm and history].
AB  - After a brief discussion of the concept of statistical, social and functional
      norm, the authors stress that the latter is related to the constant evolution and
      hence uncertain nature of scientific knowledge. With regard to mental disease it
      is underlined that, during the history of psychiatrics, social aspects have often
      been confused with functional ones, and uncommon statistical aspects have been
      interpreted as abnormal. Likewise, as it changes over time even the social norm
      has interfered with functional norms and consequently with the pathological
      process.

PMID- 7643738
TI  - [Recurrent brief depression].
AB  - The initial conception of manic depressive illness by Kraepelin included short
      and mild depressive and hypomanic states in the nosologic category of affective
      illness. The concept of recurrent brief depression was further confirmed in
      recent community and general practice studies. The diagnostic criteria for
      recurrent brief depression requires the presence of at least five of nine
      depressive symptoms analogous to the symptoms of major depression, yet a duration
      of less than two weeks (in general 1 to 3 days), a recurrence of at least 12
      times a year, and the evidence of work impairment. The 1-year prevalence in the
      general population is about 5% and the lifetime prevalence 16%. Recurrent brief
      depression may develop into major depression and vice versa in about the same
      percentage of cases. Patients with combined major and recurrent brief depression
      are more severely affected, have a higher suicide attempt rate, and have an
      increased frequency of treatment--seeking than patients with only one condition.
      Recurrent brief depression is typically characterized by monthly occurring short
      lived depressive episodes, with an erratic, relapsing and chronic course and
      significant suicide risk. The duration of these episodes in clinical samples was
      of 3-5 days on average, with a medium number of episode a year of 20. The onset
      of episodes is sudden and patients progress rapidly to the severe levels of
      depression. Resolution of the symptoms also tends to be rapid. The suddeness of
      the episodes may contribute to the relationship reported with suicidal behaviour.
      This is a disabling illness because of the frequency with which the episodes
      recur reported as erratic "irregularly regular".(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7643739
TI  - [Making real].
AB  - OBJECT: This paper has the aim to explore psychopathological traits of anorexia
      nervosa leading to somatization, in critical periods of this disorder, in the
      clinical framework of analytically oriented psychotherapy performed in hospital
      setting. DESIGN: Psychodynamic observations in high risk cases, with at least
      three years of follow-up, are compared with different crisis situations, of
      psychosomatic or psychic nature. Common and specific psychopathologic features
      are outlined. BACKGROUND: General Hospital background, liaison problems, and
      integrative needs between medical and psychotherapeutic caregivers are not only
      aspects of real situation, but also a group matrix of change for anorexic
      patients. PATIENTS: Twelve high risk subjects with restricting anorexia were
      studied, out of a sample of 36 women with eating disorders, admitted to hospital
      between 1989 and 1991. They were treated by integrated psychotherapeutic and
      medical methods, in a supportive, unprescriptive therapy plan. RESULTS:
      Psychosomatic crisis points out that the process that makes real death risks and
      fantasies is both intrapsychic and interpersonal one. Absence of a cohesive inner
      organization leads patients to try to establish fusion with other and to search
      for cohesion in hospital field turning away from adaptive integration in real
      life. Psychotherapy, in this setting, is a first movement of integrating identity
      as separate from family and field. From doctor's point of view, to be only
      concretely oriented involves the risk of losing patient's thought dimension, and,
      from psychotherapist's point of view, to pay attention only to mind or
      interactions involves the risk of losing real subject's and field's coordinates.
      Converging attention and investment by both caregivers seem to rapidly reverse
      somatization process and to help a first step of integration by the anorexic
      patients.

PMID- 7643740
TI  - [Assessment of autism and pervasive developmental disorders: a selective review
      of behavior rating scales].

PMID- 7643741
TI  - The Escherichia coli K88 periplasmic chaperone FaeE forms a heterotrimeric
      complex with the minor fimbrial component FaeH and with the minor fimbrial
      component FaeI.
AB  - K88ab fimbriae are long polymeric protein structures mainly composed of FaeG
      proteins. The Escherichia coli K88 periplasmic chaperone FaeE is a homodimer and
      forms a heterotrimeric complex with the K88 major fimbrial component FaeG in the
      periplasm. In this study the direct interaction of FaeE and the minor K88
      fimbrial subunits FaeH and FaeI were investigated. The faeH gene and the faeI
      gene were subcloned in a pINIIIA1-derivative vector containing the faeE gene. SDS
      PAGE using normal and gradient gels and immunoblotting revealed that the
      subcloned genes were expressed in the periplasm. Analyses of periplasmic
      fractions by native gel electrophoresis and isoelectric focusing (IEF) showed
      that FaeE and FaeH, as well as FaeE and FaeI formed protein complexes. These
      complexes were isolated and purified by FPLC or IEF and native gel
      electrophoresis. The stoichiometry of the proteins in these complexes was studied
      by automated Edman degradation and gel image analysis. The results showed that
      FaeE and FaeH, and FaeE and FaeI formed heterotrimeric E2H and E2I complexes,
      respectively. In addition to the E2H complex, cells expressing FaeE and FaeH
      accumulated unbound FaeH in their periplasm. In contrast to the E2G complex, the
      purified E2H complex was not stable and was partly dissociated in the
      experimental conditions used, suggesting that the interaction between FaeE and
      FaeH is not as strong as the interaction of FaeE and FaeG.

PMID- 7643742
TI  - Phenotypic variation in Haemophilus influenzae: the interrelationship of colony
      opacity, capsule and lipopolysaccharide.
AB  - H. influenzae type b strains show phase variation between opaque (O) and
      translucent (T) colony phenotypes. These phenotypic differences have been related
      to differences in virulence for infant rats. This study shows that the switch
      between O and T colony phenotypes is associated with variation in the amount of
      cell-associated capsule in the serotype b strains Rd:b+:01, RM7004 and Eagan. O
      colonies comprised organisms which were more serum resistant and had more cell
      associated polyribosyl ribitol phosphate (PRP) than organisms from T colonies.
      Strain Rd, the non-encapsulated parent of the encapsulated transformant Rd:b+:01,
      was constitutively translucent, consistent with its lack of capsule expression.
      Since previous studies had correlated O-T switching with differences in the
      relative molecular weight of lipopolysaccharide (LPS), LPS phenotypes of Rd and
      Rd:b+:01 were compared and correlated with opacity phenotype at the individual
      colony level. Both strains showed phase variation between higher and lower
      molecular weight LPS oligosaccharide structures but the prevalence of higher
      molecular weight LPS was greater for the capsule-deficient Rd than encapsulated
      Rd:b+01. Capsule-deficient mutants of strains Rd:b+:01, RM7004 and Eagan produced
      constitutively translucent colonies and each had a greater prevalence of higher
      molecular weight LPS than their encapsulated parents. These findings indicated an
      incomplete association between capsular O-T phase variation and LPS expression.

PMID- 7643743
TI  - Virulence of Streptococcus pneumoniae in mice: a standardized method for
      preparation and frozen storage of the experimental bacterial inoculum.
AB  - Animal models of pneumococcal infection are important to evaluate the protective
      capacity of new vaccine candidates. We have established a method to prepare and
      store the experimental inoculum without loss of virulence or number of bacteria.
      This allows a standardized inoculum from the same culture batch to be used in
      several experiments. Pneumococci were cultured to mid-logarithmic growth phase in
      Todd-Hewitt broth with 17% fetal calf serum. The bacterial broth was distributed
      into smaller volumes and immediately frozen on liquid nitrogen and stored at -70
      degrees C. We have tested the virulence of five different pneumococcal serotypes
      in BALB/c, C57BL/6, and NIHS mice using inocula prepared by this method and
      stored without loss of virulence for up to 4 years. Serotypes 1, 4, 5 and 8 were
      highly virulent for the strains of mice tested whereas type 6B showed lower
      virulence and a peculiar, protracted course of infection. There were no clear
      differences in virulence between the different strains of mice with the exception
      of serotype 6B, which showed higher virulence in BALB/c and NIHS mice than in
      C57BL/6 mice.

PMID- 7643744
TI  - Induction of interleukin 1 alpha in murine macrophages infected in vitro with
      different species and strains of Leishmania.
AB  - It is now generally agreed that several cytokines released by immunocompetent
      cells such as macrophages play a crucial role in the outcome of infections caused
      by protozoa belonging to the genus Leishmania. In particular, tumor necrosis
      factor (TNF) induction during the course of cutaneous leishmaniasis has been
      related to resistance to L. major infection in mice. However, the role played by
      interleukin 1 (IL-1) in the host response to leishmaniasis has yet to be
      completely elucidated. The aim of this work was to study whether different
      species and strains of Leishmania could induce IL-1 alpha in murine macrophages
      in vitro. Resident peritoneal macrophages of BALB/c and C3H/HeN mice were
      infected with L. donovani, L. major, or different strains of L. infantum. It was
      found that L. donovani did not induce IL-1 alpha in macrophages from either mice
      strain. Infection with L. major or with three out of six strains of L. infantum
      induced consistent amounts of IL-1 alpha, but only in macrophages from
      genetically resistant C3H/HeN mice. No relationship was found between the rate of
      infection of macrophages and the amount of IL-1 alpha detected in the
      supernatants of infected macrophages. Data obtained confirm that the release of
      IL-1 alpha by murine macrophages infected in vitro with Leishmania is influenced
      by the genetic background of the cells as well as by the parasite species.

PMID- 7643745
TI  - Investigations into the molecular basis of meningococcal toxicity for human
      endothelial and epithelial cells: the synergistic effect of LPS and pili.
AB  - Using human umbilical vein endothelial cells as an in vitro model of toxicity, it
      was found that Neisseria meningitidis, Neisseria gonorrhoeae, Neisseria lactamica
      and Neisseria sicca caused damage to these cells, in contrast to the lack of
      cytotoxicity exhibited by Haemophilus influenzae type b. N. meningitidis was also
      found to be toxic for human epithelial cells. The major toxic factor of N.
      meningitidis was found to be a heat-stable component of outer membrane vesicles,
      and could be inhibited by polymyxin B, suggesting that lipopolysaccharide plays a
      major role in toxicity. However, the toxicity mediated by lipopolysaccharide was
      modulated significantly by pilus-dependent adherence. Intra-strain variants
      expressing altered pilins which exhibited different levels of adherence to
      epithelial and endothelial cells were used to study the role of pilus. The degree
      of toxicity observed correlated with their relative level of adherence to
      cultured cells. In contrast, Opc-dependent increased adherence did not result in
      increased toxicity for endothelial cells, suggesting that pili have a synergistic
      effect, contributing to the overall damage.

PMID- 7643746
TI  - Whole blood model of meningococcal bacteraemia--a method for exploring host
      bacterial interactions.
AB  - An ex vivo whole blood model of meningococcal bacteraemia was developed to
      examine the total bactericidal activity of blood. Using a single defined donor
      and strains belonging to serogroups A, B and C and an unencapsulated strain, we
      demonstrated that the bactericidal mechanisms operating in whole blood varied
      with anticoagulant, serogroup and bacterial growth conditions. The choice of
      anticoagulant had a major effect on the survival of the serogroup A strain with
      94% (SEM 7.6) survival in citrated blood compared to 19.7% (SEM 19.6) survival in
      heparinised blood after 60 min incubation. The serogroup C strain showed enhanced
      survival when grown in liquid medium compared to growth on solid medium (73.5%,
      SEM 7.5, and 8.2%, SEM 3.1, respectively, in citrated blood after 60 min). The
      pattern of survival of serogroup B and the unencapsulated strain were largely
      unaffected by these variables. Comparison with cell free conditions allowed the
      contribution of cellular components in meningococcal killing to be determined.
      Secreted levels of tumour necrosis factor and neutrophil elastase secreted during
      whole blood assays did not correlate with bacterial growth or viability
      indicating a lack of relationship between killing and activation of phagocytes.

PMID- 7643747
TI  - Myocardial venous O2 saturation becomes more heterogeneous during hypoxic and
      carbon monoxide hypoxia.
AB  - The hypothesis tested was that myocardial venous O2 saturation (SvO2)
      heterogeneity, a measure of microregional O2 supply/consumption balance, would
      increase under hypoxic and CO-hypoxia conditions. Since we are able to determine
      both O2 supply and the O2 supply/consumption ratio, we could also determine
      whether regional myocardial O2 consumption was heterogeneous. Twenty open-chest
      anesthetized dogs were studied under control and four hypoxic conditions, hypoxic
      hypoxia induced by ventilation with either an 8% O2 (SaO2 = 56%) or a 6% O2 (SaO2
      = 40%) gas mixture for 20 min, or CO hypoxia induced by ventilation with a 1% CO
      gas mixture for either 7 min (SaO2 = 67%) or 20 min (SaO2 = 40%). Regional
      myocardial blood flow was measured using radioactive microspheres in 40 pieces
      (approximately 0.5 g) of the left ventricular free wall. Arterial and venous O2
      saturations were determined with a four-wavelength microspectrophotometric
      method. A total of 28 veins (20-100 microns) were examined to determine SvO2 for
      each condition within each animal. The coefficient of variation (CV = SD/mean x
      100), an index of heterogeneity, was calculated for both flow and SvO2 under each
      condition. Flow increased with increasing severity of hypoxia but its
      heterogeneity did not change with hypoxic or CO hypoxia. However, SvO2
      heterogeneity significantly increased with increasing severity of hypoxia. A
      linear regression of SvO2 CV and mean SvO2 showed a significant correlation (CV =
      -0.84 (mean SvO2) + 51.1, R = 0.59). All possible myocardial O2 consumptions were
      calculated by multiplying all of the flows and O2 extractions. In 53
      subepicardial and subendocardial measurements, only 10% of the flow and O2
      supply/consumption heterogeneity observations could be explained by uniform O2
      consumption if our acceptance criterion was 0.06-0.1 ml O2/min/100 g, and 50%
      could be explained with an acceptance criterion of 0.3-0.4 ml O2/min/100 g.
      Therefore, there must be some regional myocardial O2 consumption heterogeneity.
      The increase in venous O2 saturation heterogeneity during hypoxia may be due to
      increased variation in regional myocardial O2 consumption or variation in the
      control of O2 supply/consumption coupling.

PMID- 7643748
TI  - Regulation by basic fibroblast growth factor of glycosaminoglycan biosynthesis in
      cultured vascular endothelial cells.
AB  - The alteration of glycosaminoglycans (GAGs) in cultured bovine aortic endothelial
      cells after exposure to basic fibroblast growth factor (bFGF) was investigated.
      It was found that the incorporation of [3H]glucosamine into GAGs was markedly
      increased by bFGF in both the cell layer and the conditioned medium; however,
      that of [35S]sulfate was not changed by the growth factor. These results
      indicated that bFGF enhanced the sugar-chain formation but did not affect their
      sulfation in endothelial GAG production. Similar changes were observed in either
      bovine aortic smooth-muscle cells and human fibroblastic IMR-90 cells to greater
      and lesser degrees, respectively. Characterization of GAGs in the endothelial
      cell layer and the conditioned medium revealed that bFGF enhanced both heparan
      sulfate and the other GAGs to a similar degree. The present data suggest that
      bFGF may be involved in the regulation of the blood coagulation system via
      altering GAGs of the vascular tissue when the endothelium was damaged.

PMID- 7643749
TI  - Interferon-alpha 2b enhances barrier function of bovine retinal microvascular
      endothelium in vitro.
AB  - Increased permeability of the vascular endothelium is a critical part of
      pathological processes such as inflammation and wound healing. While several
      cytokines have been shown to increase endothelial permeability, none has been
      shown to reduce it. We studied the effect of interferon-alpha 2b on the barrier
      function of bovine retinal capillary endothelial cells in vitro and found that it
      increased the electrical resistance of the monolayers (treated cells 211 +/- 6
      ohm.cm2, untreated 109 +/- 14 ohm.cm2), decreased their permeability to inulin
      (Pc inulin of untreated cells 0.73 +/- 0.21 x 10(-6) cm/sec, treated 0.31 +/-
      0.23 x 10(-6) cm/sec, P = 0.015), and enhanced their morphological
      differentiation. Interferon-gamma had no effect. No effect of interferon-alpha
      treatment on the permeability of bovine aortic endothelial cells was found. We
      conclude that interferon-alpha 2b can enhance the barrier function of retinal
      microvascular endothelium in vitro. This is consistent with the hypothesis that
      interferon-alpha is an effector of a mechanism which actively promotes tissue
      homeostasis and suggests that it might have therapeutic potential in diseases
      characterized by leakage of the vascular endothelium.

PMID- 7643750
TI  - Effect of oxygen tension on regulation of arteriolar diameter in skeletal muscle
      in situ.
AB  - Skeletal muscle arterioles are known to constrict upon elevation of ambient PO2.
      While several studies have shown that the endothelium plays an important role in
      this response, it is not clear how this response is mediated. We examined the
      oxygen-induced constriction of arterioles in the rat spinotrapezius muscle.
      Elevation of superfusion solution PO2 from about 15 to 150 mm Hg caused
      arteriolar constriction by 25% (+/- 3%, n = 18). Inhibition of prostaglandin
      synthesis by superfusion of indomethacin (30 microM) produced vasoconstriction by
      28% (+/- 9.5%, n = 5), but left the PO2 response unaffected. Blockade of the
      synthesis of endothelium-derived relaxing factor (EDRF) by NG-nitro-L-arginine (L
      NNA, 35 mg/kg i.v.) caused arteriolar constriction by 31% (+/- 8%, n = 8). During
      application of L-NNA, the constrictor response to PO2 elevation was reduced to 3
      +/- 2%. Administration of superoxide dismutase (SOD, 80,000 U/kg i.v.) did not
      affect the PO2 response. It is concluded that in small arterioles of skeletal
      muscle both EDRF and prostanoids sustain a significant basal dilatation. The
      dilatory effects of EDRF but not of prostaglandins are strongly dependent on PO2.
      The vasoconstriction in response to high ambient PO2 is not due to EDRF breakdown
      during its diffusion from endothelial to smooth muscle cells.

PMID- 7643751
TI  - A new fluorescence microscopy for tomographic observation of microcirculation by
      using dual-beam slit laser illumination.
AB  - By designing a new epi-illumination system with dual slit laser beams, we have
      developed a fluorescence microscope for tomographic observations of in vivo
      microcirculation. Two beams of an Argon ion laser were converted into thin slit
      beams of thickness 28 to 60 microns by optical lenses and were illuminated onto
      tissue to intersect at the focal plane of the objective. The fluorescent light
      emitted from a FITC tracer by this cross-illumination was picked up by the
      microscope through a filter, with no "out of focus" noise from the tracer above
      and below the crossing zone. The results of in vitro experiments by using glass
      micropipettes (20-80 microns i.d.) filled with FITC-dextran and skeletal muscle
      tissue certified uniform tracer excitation in the crossing zone and the
      augmentation of the beam thickness due to light scattering in the tissue to be
      1.7 and 2.5 times at depths of 100 and 200 microns from the surface,
      respectively. In vivo tests in the rabbit tenuissimus muscle revealed that this
      system can realize microvasculature tomography, with adequate vertical zone
      selectivity and spatial resolution to reconstruct its three-dimensional mapping,
      and long-term monitoring of tracer leakage from a single capillary to the
      surrounding tissue, with sufficient quantitative reliability to determine the
      capillary permeability and its heterogeneity along the channel.

PMID- 7643752
TI  - Can transcutaneous oximetry detect nutritive perfusion disturbances in patients
      with lower limb ischemia?
AB  - Transcutaneous oximetry (TcpO2) performed at 37 and 44 degrees on the dorsum of
      the foot and capillary microscopy of the nailfold of the big toe were applied to
      85 patients with various (including asymptomatic) stages of lower limb ischemia
      to appreciate the relationship between (disturbances in) capillary perfusion and
      skin oxygen tension. In mildly diseased patients, capillary perfusion as measured
      by direct observation, was preserved. In critically ischemic patients in the
      supine position, red blood cell-perfused capillary density was reduced. Nutritive
      perfusion was severely reduced and showed an absent reactive hyperemia after a 1
      min arterial occlusion. Also, postural vasoconstrictive activity was reduced.
      TcpO2 measured at 37 degrees was very low already in mildly diseased patients,
      illustrating the poor oxygen diffusion toward the skin. At 44 degrees, TcpO2 was
      severely reduced in critically ischemic patients. Reactive hyperemic response and
      postural vasoconstriction were suppressed, due to local heating of the skin.
      Measurement of the TcpO2 has limitations in the assessment of nutritive
      perfusion, as opposed to capillary microscopy, since it is an indirect measure of
      skin perfusion, not necessarily derived from capillaries only. The obligatory
      local skin heating impairs physiological studies as to hyperemic reserve capacity
      or postural constriction mechanisms. Thus, transcutaneous oximetry is a poor
      method of characterizing pathophysiological mechanisms occurring in skin
      nutritive microcirculation. However, capillary microscopy and transcutaneous
      oximetry can give additive information as to the severity of peripheral ischemia.
      Peak red blood cell velocity during reactive hyperemia using capillary microscopy
      and the resting TcpO2 at 44 degrees, both measured in the supine position,
      appeared to be valuable microcirculatory parameters in detecting critical limb
      ischemia.

PMID- 7643753
TI  - Vascular endothelium and smooth muscle remodeling accompanies hypertrophy of
      intestinal arterioles in streptozotocin diabetic rats.
AB  - The purpose of this study was to document alterations in endothelial and smooth
      muscle cell morphology of first- and second-order intestinal arterioles after 6
      months of streptozotocin-induced diabetes. Both light and scanning electron
      microscopic techniques were used to quantitate the changes in the
      microvasculature. After rendering the first- and second-order intestinal
      arterioles passive and processing the vessels, it was determined that these
      microvessels were significantly dilated in the diabetic animals. Further
      examination revealed that in the diabetic animals, the cross-sectional area of
      the endothelial layer was increased in both 1A and 2A vessels, and the smooth
      muscle layer cross-sectional area was significantly increased in 1A vessels.
      Individual smooth muscle cells were significantly increased in width in the
      diabetic animals, but not in length. These data suggest that in this model of
      diabetes in rats, intestinal arteriolar hypertrophy was accompanied by
      significant remodeling of the arteriolar wall.

PMID- 7643754
TI  - Phosphatidylcholine hydrolysis and DNA synthesis in cultured retinal capillary
      pericytes.
AB  - In order to verify the role of activation of phosphatidylcholine (PC) hydrolysis
      by phospholipase D (PLD) in the initiation of mitogenic process of retinal
      capillary pericytes, platelet-derived growth factor (PDGF), a known PC hydrolysis
      stimulator, and exogenous PLD have been used to stimulate pericytes. Exogenous
      PLD (Streptomyces chromofuscus PLD) or PDGF BB homodimer (PDGF) was added to a
      medium of quiescent pericytes prelabeled with [32P]orthophosphate. In the
      presence of ethanol (300 mM), phosphatidic acid (PA) and its stable
      transphosphatidylated product, phosphatidylethanol (PEt), were determined. In
      parallel, [3H]thymidine incorporation was measured. Downregulation of PKC was
      achieved by long-term treatment with a phorbol ester. The addition of exogenous
      PLD or PDGF stimulated both [3H]thymidine incorporation and [32P]PEt formation in
      a similar kinetic fashion, suggesting that PC hydrolysis is involved in PDGF
      mitogenic signaling pathway. PDGF-stimulated [3H]PA formation was significantly
      higher in the presence than in the absence of PA phosphohydrolase (PAP)
      inhibitor, indicating the activation of PLD/PAP pathway. In the presence of
      ethanol, a substantial level of PA at the steady state can be abolished by an
      inhibitor of diacylglycerol (DAG) kinase. This phenomenon indicates the existence
      of PC-phospholipase C (PLC)/DAG kinase pathway in PC hydrolysis. Insulin
      potentiated both PLD- and PDGF-induced DNA synthesis. Though similarities occur
      in the induction of DNA synthesis and PC hydrolysis by exogenous PLD and PDGF,
      the maximum extent of DNA synthesis of exogenous PLD was only approximately 43%
      of that induced by PDGF. Moreover, exogenous PLD-induced DNA synthesis was not
      blunted, while PDGF-elicited DNA synthesis was markedly reduced, by PKC
      downregulation. In addition, PDGF-induced PC hydrolysis was attenuated by a
      tyrosine kinase inhibitor, whereas exogenous PLD-induced PC hydrolysis was
      unchanged. Taken together, exogenous PLD may mimic PDGF action and partially
      account for the efficacy on DNA synthesis elicited by PDGF. The signal
      transduction initiated by exogenous PLD is able to bypass the PKC- and PTK
      dependent activation of endogenous PLD. These findings provide evidence for the
      importance of PLD-mediated PC hydrolysis in pericyte DNA synthesis stimulated by
      PDGF.

PMID- 7643755
TI  - Effects of human alpha-thrombin and 8bromo-cAMP on large and microvessel
      endothelial monolayer equivalent "pore" radii.
AB  - Previous studies have reported that endothelial cells isolated from large vessels
      compared with microvessels from the same or distinct organs showed considerable
      phenotypic and biochemical heterogeneity. In the present study we extend these
      findings by comparison of the effects of 8-bromo-cyclic adenosine monophosphate
      (8Br-cAMP), human alpha-thrombin, 8Br-cAMP followed 5 min later by thrombin or no
      treatment (control) on the equivalent "pore" radii (rp) of endothelial monolayers
      isolated from the main bovine pulmonary artery (BPAEC) compared with lung
      microvessels (BLMV). BLMV, isolated from a 1-cm peripheral segment of the lung,
      were significantly larger than those obtained from large vessels (1602 +/- 142
      microns2 vs 398 +/- microns2, respectively). In addition, BLMV monolayers formed
      a heteroporous barrier with less size-selectivity compared with BPAEC monolayers.
      8Br-cAMP caused monolayers of both cell types to close their large "pores" which
      completely restricted the passage of solute molecular radii > 35-60 A across
      these barriers, consistent with a rp of approximately 75-100 A. This effect was
      due to a reduction in the area available for solute exchange (Ap) and/or an
      increase in the path length of the transport pathway (delta X). Human alpha
      thrombin produced an increase in the Ap/delta X consistent with the formation of
      large open areas between adjacent cells that exposed the approximately 2000 A
      pore radius of the filter support. Since this effect was more marked in
      microvessel compared with large vessel monolayers, microvessel endothelial cells
      appear to be more sensitive to the effects of thrombin.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7643756
TI  - The diabetes epidemic in Australia: prevalence, patterns and the public health.

PMID- 7643757
TI  - Infection control in Australia.

PMID- 7643758
TI  - Economic debate about smoking.

PMID- 7643759
TI  - Children of parents with psychotic disorders.

PMID- 7643760
TI  - Reporting of occupational exposures to blood-borne pathogens in Australian
      teaching hospitals.
AB  - OBJECTIVE: To describe the reporting of occupational exposures to blood and body
      fluids in Australian teaching hospitals. DESIGN: Survey by questionnaire of the
      major teaching hospitals in Australia, December 1992. RESULTS: Completed
      questionnaires were received from 88% of the 69 teaching hospitals in Australia.
      All responding hospital reported an established procedure for reporting and
      managing occupational exposures to blood and body fluids and 82% indicated
      willingness to contribute data to a national monitoring project. Information
      concerning the actual incident was recorded by all hospitals and two-thirds of
      hospitals had forms which specifically detailed exposures history. Patient and
      healthcare worker risk factors for HIV were recorded less frequently. but in 87%
      of hospitals blood tests were performed on both the staff member and source
      patient. Among 87 026 equivalent full time staff employed by the responding
      hospitals, 5803 injuries were reported in 1991. The median number of reported
      injuries as a percentage of equivalent full time staff was 7%. Estimates of non
      reporting ranged from 5% to 70% (median 25%). Prophylactic zidovudine was
      prescribed for 50 staff from 21 hospitals in 1991. CONCLUSIONS: All Australian
      teaching hospitals have an established procedure for documenting occupational
      exposure to blood and body fluids. Although there is limited standardisation at a
      national level, the information already collected and the willingness to
      participate indicated by a large number of teaching hospitals are sufficient for
      a national surveillance mechanism to be established.

PMID- 7643761
TI  - Prevalence of psychiatric disorders in rural South Australia.
AB  - OBJECTIVE: To determine the prevalence of psychiatric disorders and use of
      medical services in a South Australian rural community. DESIGN: Survey based on
      structured self-administered questionnaires. SETTING: Riverland region of South
      Australia, between May and November, 1991. SUBJECTS: A probability sample of 1009
      residents (71.1%) response stratified for age and sex (with replacement) aged 18
      years and over from the State electoral roll. OUTCOME MEASURES: DSM-III-R-defined
      psychiatric disorders diagnosed by means of the University of Washington's
      Diagnostic Interview Schedule Screening Instrument (DISSI), physical disorders
      and use of health and allied services. RESULTS: Twenty-six percent had at least
      one psychiatric disorder in the six months before interview. Prevalence did not
      differ with sex or age, but was higher in the unemployed (P=0.0001). Those with a
      current psychiatric disorder were significantly more likely to report a lifetime
      physical disorder (p=0.0001). The most common disorders were major depression and
      dysthymia (10.8%), anxiety disorder (9.8%), phobic disorder (7.8%), alcohol abuse
      and dependence (7.0% and somatisation syndrome (5.3 During the year before
      interview, 88.5% of those diagnosed with a current psychiatric disorder had
      consulted a general practitioner and 4.2% a psychiatrist or psychologist.
      CONCLUSIONS: The prevalence of psychiatric disorders in the Riverland region was
      comparatively high. General practitioners were the primary care-providers for
      those with psychiatric disorders. These issues need to be addressed by service
      providers and health planners.

PMID- 7643762
TI  - 1989-90 National Health Survey: prevalence of self-reported diabetes in
      Australia.
AB  - OBJECTIVE: To estimate the prevalence of self-reported diabetes in a
      representative population sample in Australia; to identify major differences in
      prevalence by State and Territory and by geographic origin; and to compare trends
      in prevalence over time. DESIGN: and setting: Analysis of data collected by the
      Australian Bureau of Statistics in the 1989-90 National Health Survey. The
      sampling frame (22,202 households and 54,241 people) ensured adequate
      representation from each State and Territory in Australia. RESULTS: Prevalences
      of self-reported diabetes/high blood sugar levels were 1.9% for males and 2.0%
      for females over all ages; 3.1% for men and 2.9% for women aged over 25 years;
      and 8.1% for men and 6.9% for women aged over 65 years. Interstate differences of
      borderline significance were found and will require validation in larger samples.
      Age-standardised prevalences were higher in subjects born in Southern Europe and
      lower in those born in Western Europe compared with Australian-born subjects.
      Prevalences were high in households where the language spoken was other than
      English. The frequency of self-reported diabetes appears to be rising.
      CONCLUSIONS: Australia has comparatively low total prevalences of self-reported
      diabetes/high blood sugar levels. High prevalences subsections exist, including
      the elderly and certain migrant groups

PMID- 7643763
TI  - Inflammatory bowel disease: a retrospective review of a specialist-based cohort.
AB  - OBJECTIVE: To study the morbidity and mortality of inflammatory bowel disease in
      Australia and whether it decreases life expectancy. DESIGN: A retrospective
      review of patient case notes from two Sydney teaching hospitals and the
      consulting rooms of the 17 gastroenterologists appointed to these hospitals,
      examining all presentations with a diagnosis of inflammatory bowel disease from
      January 1977 to September 1992. RESULTS: 997 cases were identified: 533 with
      ulcerative colitis, 417 with Crohn's disease, and 47 with indeterminate colitis.
      In patients diagnosed from 1977 onwards (n = 730), no difference in survival was
      demonstrated for inflammatory bowel disease overall, or any subgroup, or in males
      or females, as compared with an age- and sex-matched control population.
      Gastrointestinal malignancies occurred in 19 cases (18 colorectal carcinoma and
      one cholangiocarcinoma). The most commonly encountered problems were the use of
      immunosuppressants and the need for surgery. Inflammatory bowel disease,
      particularly Crohn's disease, entails appreciable morbidity. CONCLUSION: Since
      1977, despite a significant requirement for medical and surgical treatment in
      patients with inflammatory bowel disease, there has been no adverse effect on
      survival in a specialist-referred cohort as compared with the general population.

PMID- 7643764
TI  - Prospective study of diarrhoeal outbreaks in child long-daycare centres in
      western Sydney.
AB  - OBJECTIVE: To investigate outbreaks of diarrhoeal illness in children attending
      long-daycare centres (LDCs), to characterise parasitic, bacterial and viral
      isolates from the children's faeces and to identify individual and LDC risk
      factors for diarrhoea. DESIGN: Eleven-month prospective case-control study of
      diarrhoeal outbreaks among children in LDCs. SUBJECTS: 2368 children attending 35
      LDCs in the western Sydney area. MAIN OUTCOME MEASURES: Frequency of diarrhoeal
      outbreaks, rate of attack and spread to family members; pathogens isolated from
      stools; and individual and LDC risk factors. RESULTS: The overall incidence of
      diarrhoeal disease was low (0.28 outbreaks per centre per year and 0.056 outbreak
      associated cases per child-year). Attack rates during outbreaks varied widely (4%
      55%; mean, 15%), as did secondary spread rates to family members (1%-15%; mean,
      9%). Pathogens were isolated from 7% of symptomatic children and 7% of controls;
      no outbreak was shown to be caused by a recognised pathogen. Children with
      outbreak-associated diarrhoeal illness were more likely to have suffered
      vomiting, poor appetite, lack of energy, fever and to have taken antibiotics in
      the previous week than other children. Hygiene practices varied widely among
      centres. CONCLUSIONS: We found low incidence and morbidity from diarrhoeal
      illness in Australian urban LDCs. Diarrhoea in children in LDCs may be caused
      predominantly by non-infectious factors such as diet and antibiotic exposure.
      Current hygiene measures in LDCs seem adequate to prevent and contain outbreaks
      of infectious diarrhoea.

PMID- 7643765
TI  - The economic rationalists strike again.

PMID- 7643766
TI  - Clinical practice guidelines.

PMID- 7643767
TI  - Youth suicide.

PMID- 7643768
TI  - Somatisation disorder: a major public health issue.

PMID- 7643769
TI  - Cushing's syndrome: how should we investigate in 1995?

PMID- 7643770
TI  - Non-steroidal anti-inflammatory drugs.
AB  - The elderly are at higher risk of adverse reactions from non-steroidal anti
      inflammatory drugs (NSAIDs), including those due to drug interactions, than
      younger people. Before prescribing oral NSAIDs in the elderly, the clinician
      should consider other forms of therapy and topical NSAIDs. When an oral NSAID is
      used, the dose should be minimised and the need for treatment reviewed
      periodically to reduce duration of therapy. NSAIDs with a high risk of toxicity
      (such as phenylbutazone, salicylates, piroxicam and indomethacin) should be
      avoided in the elderly.

PMID- 7643771
TI  - Prostate cancer: enthusiasm for screening.

PMID- 7643773
TI  - Leiomyosarcoma of the uterus in a woman taking adjuvant tamoxifen therapy.

PMID- 7643772
TI  - Prostate cancer: enthusiasm for screening.

PMID- 7643774
TI  - Providing information and obtaining signed consent to cancer treatment.

PMID- 7643775
TI  - Postoperative adrenal haemorrhage complicating a multifactorial coagulopathy.

PMID- 7643776
TI  - Changed indications for Parlodel (bromocriptine) for lactation suppression.

PMID- 7643777
TI  - HIV exposure in health care.

PMID- 7643778
TI  - Parents' perceptions of infants' reactions to vaccination.

PMID- 7643779
TI  - Measles outbreak in western Sydney.

PMID- 7643780
TI  - A case of Queensland tick typhus.

PMID- 7643781
TI  - Tracheo-oesophageal compression due to rapid thyroid enlargement after
      radioiodine treatment.

PMID- 7643782
TI  - Congenital hypothyroidism: check the siblings.

PMID- 7643783
TI  - The euthanasia controversy. Decision making in extreme circumstances.

PMID- 7643784
TI  - Higher awards for personal injuries.

PMID- 7643785
TI  - Calculation of stopping-power ratios using realistic clinical electron beams.
AB  - The Spencer-Attix water/air restricted mass collision stopping-power ratio is
      calculated in realistic electron beams in the energy range from 5-50 MeV for a
      variety of clinical accelerators including the Varian Clinac 2100C, the Philips
      SL75-20, the Siemens KD2, the AECL Therac 20, and the Scanditronix Medical
      Microtron 50. The realistic clinical beams are obtained from full Monte Carlo
      simulations of the clinical linear accelerators using the code BEAM. The stopping
      power ratios calculated using clinical beams are compared with those determined
      according to the AAPM and the IAEA protocols which were calculated by using
      monoenergetic parallel beams. Using the energy-range relationship of Rogers and
      Bielajew [Med. Phys. 13, 687-694 (1986)] leads to the most consistent picture in
      which the stopping-power ratios at dmax derived from mono-energetic calculations
      underestimate the stopping-power ratios calculated with the realistic beam by
      0.3% at 5 MeV and up to 1.4% at 20 MeV. The stopping-power ratios at dmax
      determined according to the AAPM TG-21 protocol (1983) are shown to overestimate
      the realistic stopping-power ratios by up to 0.6% for a 5-MeV beam and
      underestimate them by up to 1.2% for a 20-MeV beam. Those determined according to
      the IAEA (1987) protocol overestimate the realistic stopping-power ratios by up
      to 0.3% for a 5-MeV beam and underestimate them by up to a 1.1% for a 20-MeV beam
      at reference depth. The causes of the differences in the stopping-power ratios
      between the realistic clinical mono-energetic beams are analyzed quantitatively.
      The changes in the stopping-power ratios at dmax are mainly due to the energy
      spread of the electron beam and the contaminant photons in the clinical beams.
      The effect of the angular spread of electrons is rather small except at the
      surface. Data are presented which give the corrected stopping-power ratios at
      dmax or reference depth starting from those determined according to protocols for
      any energy of clinical electron beams with scattering foils. For scanned clinical
      electron beams the correction to stopping-power ratios determined according to
      protocols is found to be less than 0.5% at dmax or reference depth for all beam
      energies studied. We quantify the differences in the stopping-power ratios
      determined using the depth of 50% ionization level and the depth of 50% dose
      level. The differences are very small except for very-high-energy beams (50 MeV)
      where they can be up to 0.8%.

PMID- 7643786
TI  - BEAM: a Monte Carlo code to simulate radiotherapy treatment units.
AB  - This paper describes BEAM, a general purpose Monte Carlo code to simulate the
      radiation beams from radiotherapy units including high-energy electron and photon
      beams, 60Co beams and orthovoltage units. The code handles a variety of
      elementary geometric entities which the user puts together as needed (jaws,
      applicators, stacked cones, mirrors, etc.), thus allowing simulation of a wide
      variety of accelerators. The code is not restricted to cylindrical symmetry. It
      incorporates a variety of powerful variance reduction techniques such as range
      rejection, bremsstrahlung splitting and forcing photon interactions. The code
      allows direct calculation of charge in the monitor ion chamber. It has the
      capability of keeping track of each particle's history and using this information
      to score separate dose components (e.g., to determine the dose from electrons
      scattering off the applicator). The paper presents a variety of calculated
      results to demonstrate the code's capabilities. The calculated dose distributions
      in a water phantom irradiated by electron beams from the NRC 35 MeV research
      accelerator, a Varian Clinac 2100C, a Philips SL75-20, an AECL Therac 20 and a
      Scanditronix MM50 are all shown to be in good agreement with measurements at the
      2 to 3% level. Eighteen electron spectra from four different commercial
      accelerators are presented and various aspects of the electron beams from a
      Clinac 2100C are discussed. Timing requirements and selection of parameters for
      the Monte Carlo calculations are discussed.

PMID- 7643787
TI  - Mean mass energy absorption coefficient ratios for megavoltage x-ray beams.
AB  - Mean mass energy absorption coefficient ratios of acrylic, polystyrene, and water
      to air, were calculated using Monte Carlo generated energy spectra. The energy
      spectra were calculated for 4- to 50-MV x-ray beams, from machines using
      flattening filters and scanning beams. The validity of these spectra was verified
      by comparing the measured ionization ratios with the calculated values. The
      agreement was found to be within 1.9%. For beams of energy below 6 MV, our
      estimates of the mean mass energy absorption coefficient ratios agree well with
      those recommended by the TG-21 protocol. For higher energy beams, the discrepancy
      increases to about 3%. It was found that the discrepancy is attributable to the
      different spectra used in these calculations.

PMID- 7643788
TI  - Electron mass scattering powers: Monte Carlo and analytical calculations.
AB  - Values of electron mass scattering power, T/p, for various materials have been
      calculated by using the EGS4 Monte Carlo system and by integration of the Moliere
      multiple-scattering distribution. The energy range covered is 0.5-100 MeV. Monte
      Carlo calculations test the concept of T/p "experimentally" and assess the
      contribution to electron mass scattering power from effects such as Moller
      scatter and energy-loss straggling. The Monte Carlo results agree within 2% with
      the analytical results calculated from Moliere multiple-scattering theory at
      energies less than 20 MeV for high-Z materials and for energies less than 50 MeV
      for low-Z materials. At higher energies the Monte Carlo calculations include the
      effects of bremsstrahlung production which can significantly increase values of
      T/p. For low-Z materials and electron energies less than 60 MeV, the Monte Carlo
      calculated T/p values are generally 22% higher than those given by ICRU Report
      35, while those for high-Z materials and energies less than 25 MeV are found to
      be consistent (within 1%) with ICRU Report 35. The effects of Moller scatter,
      which significantly affect T/p for low-Z materials, as well as bremsstrahlung
      effects, are included in the present Monte Carlo calculations. If the tabulated
      T/p data of ICRU Report 35 are modified to include the Moller scatter effect,
      then for energies less than 60 MeV they are generally 6% less than the present
      Monte Carlo data for low-Z materials as well as for copper. It is shown that T/p
      is a well-defined constant over an appropriate range of slab thickness except
      when bremsstrahlung effects are significant. It is found that T/p is proportional
      to E-n, where n is in the range of 1.5-2.0 for the energies considered here. The
      Monte Carlo calculations are shown to agree well with various relevant
      experimental measurements. Accurate T/p data, which should include the effect of
      Moller scatter, are necessary in electron-beam treatment planning, especially for
      a small field size. The choice of the depth step in the implementation of pencil
      beam codes should not violate the slab-thickness limits for T/p data.

PMID- 7643789
TI  - A new sigmoidal function describing the small field dose profile data from a
      linear accelerator.
AB  - Dose profile data from small circular fields have been used in treatment dose
      planning for stereotactic radiosurgery. Generally, a two-dimensional
      interpolation of the measured beam profiles from circular collimators is used to
      calculate the dose at any axial depth and radial distance from the central axis.
      Instead, the dose profile data can be transformed into a sigmoidal form. A new
      three parameter sigmoidal function was developed to fit the transformed
      (sigmoidal) dose profile data. The values of the three estimated parameters were
      found to follow either linearly or exponentially as a function of axial depth.
      Thus, instead of linear interpolation, these formulas can be used to calculate
      dose at any axial depth and radial distance from the central axis for circular
      collimators of various diameters. This new sigmoidal function provides another
      formula to describe dose profile data from circular collimator of small fields.

PMID- 7643790
TI  - Measurements and calculations of the absorbed dose distribution around a 60Co
      source.
AB  - The data from Meisberger et al. [Radiology 90, 953-957 (1968)] are often used as
      a basis for dose calculations in brachytherapy. In order to describe the absorbed
      dose in water around a brachytherapy point source, Meisberger provided a
      polynomial fit for different isotopes taking into account the effect of
      attenuation and scattering. The validity of the Meisberger coefficients is
      restricted to distances up to 10 cm from the source, which is regarded to be
      satisfactory for most brachytherapy applications. However, for more distant
      organs it may lead to errors in calculated absorbed dose. For this reason dose
      measurements have been performed in air and in water around a high activity 60Co
      source used in high dose rate brachytherapy. Measurements were carried out to
      distances of 20 cm, using ionization chambers. These data show that at a distance
      of about 15 cm the amount of scattered radiation virtually equals the amount of
      primary radiation. This emphasizes the contribution of scattered radiation to the
      dose in healthy tissue far from the target volume, even with relatively high
      energy photon radiation of 60Co. It is also shown that the Meisberger data as
      well as the approach of Van Kleffens and Star [Int. J. Radiat. Oncol. Phys. 5,
      557-563 (1979)] lead to significant errors in absorbed dose between distances of
      10 and 20 cm from the source. In addition to these measurements, the Monte Carlo
      code has been used to calculate separately primary dose and scattered dose from a
      cobalt point source. The calculated results agree with the experimental data
      within 1% for a most distant dose scoring region.

PMID- 7643791
TI  - Instrumentation and dosimeter-size artifacts in quantitative thermoluminescence
      dosimetry of low-dose fields.
AB  - Thermoluminescence dosimetry is extensively used for quantitative dose
      measurements in various irradiation fields such as dosimetry of brachytherapy
      sources. In this application, small doses on the order of 0.5 cGy must be
      accurately measured, which requires careful control of instrumentation, energy
      dependence, and nonlinearity of detector response. Several investigators have
      observed the presence of some undesirable signals when the thermoluminescent
      dosimeters (TLDs) were read without any nitrogen gas flow in the TLD reader.
      Others have indicated that the "prereadout" annealing technique is the same as
      the "preirradiation" technique for doses above 10 cGy, but they have not extended
      their study to lower doses. The goal of this study is to investigate dependence
      of sensitivity and linearity of the TLD response to the flow of nitrogen gas in
      the TLD reader at low dose level, annealing technique, and TLD size. The effect
      of nitrogen flow sensitivity and linearity of two different sizes of lithium
      fluoride TLD-100 chips has been studied. Our data indicate a large standard
      deviation of TLD sensitivity, up to a factor of 2, when TLDs were read without
      nitrogen gas flow in the TLD reader. In addition, a large deviation from
      linearity was observed for doses below 5 cGy. When the reading-chamber was purged
      with nitrogen gas, dispersion of the responses of the TLDs that were exposed to
      the same dose fell to within 5%. At precision levels of 2% and 5%, the low dose
      limits are 1 cGy and 0.5 cGy, respectively, for large chips and 15 cGy and 1 cGy
      for small chips, if TLDs are read with nitrogen gas flow in the TLD
      reader.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7643792
TI  - Mechanical and dosimetric quality control for computer controlled radiotherapy
      treatment equipment.
AB  - Modern computer controlled radiotherapy treatment equipment offers the
      possibility of delivering complex, multiple field treatments with minimal
      operator intervention, thus making multiple field conformal therapy practical.
      Conventional quality control programs are inadequate for this new technology, so
      new quality control procedures are needed. A reasonably fast, sensitive, and
      complete daily quality control program has been developed in our clinic that
      includes nearly automated mechanical as well as dosimetric tests. Automated
      delivery of these quality control fields is performed by the control system of
      the MM50 racetrack microtron, directed by the CCRS sequence processor [D. L.
      McShan and B. A. Fraass, Proceedings of the XIth International Conference on the
      use of computers in Radiation Therapy, 20-24 March 1994, Manchester, U.K. (North
      Western Medical Physics Department, Manchester, U.K., 1994), pp. 210-211], which
      controls the treatment process. The mechanical tests involve multiple
      irradiations of a single film to check the accuracy and reproducibility of the
      computer controlled setup of gantry and collimator angles, table orientation,
      collimator jaws, and multileaf collimator shape. The dosimetric tests, which
      involve multiple irradiations of an array of ionization chambers in a commercial
      dose detector (Keithly model 90100 Tracker System) rigidly attached to the head
      of the treatment gantry, check the output and symmetry of the treatment unit as a
      function of gantry and collimator angle and other parameters. For each of the
      dosimetric tests, readings from the five ionization chambers are automatically
      read out, stored, and analyzed by the computer, along with the geometric
      parameters of the treatment unit for that beam.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7643793
TI  - Evaluation of the dosimetric characteristics of a diamond detector for photon
      beam measurements.
AB  - The dosimetric properties of a new diamond detector for the measurement of
      relative dose in photon beams have been investigated and compared to those of a
      silicon p-type photon diode and a 0.14 cm3 ionization chamber. The mass energy
      absorption ratio of carbon to water is nearly constant over a wide energy range
      making the diamond detector nearly tissue equivalent. The directional dependence
      of the radiation response of the diamond detector for cobalt 60, 6 MV and 18 MV
      photon beams was more uniform than that of the diode. As the incident photon beam
      moves from 0 degree (parallel to the detector stem) to a direction transverse to
      the detector stem (90 degrees), the diamond detector sensitivity remains nearly
      uniform whereas the diode sensitivity diminishes by approximately 15%-22%. The
      spatial resolution of the diamond detector, as measured by penumbra width, is
      slightly less than that of the diode detector but clearly superior to that of the
      0.14 cm3 ionization chamber. The tissue maximum ratio measurements for small size
      photon fields (diameter < or = 4 cm) with the diamond, diode, and a Markus
      parallel plate chamber are in excellent agreement. The diamond detector with high
      radiation sensitivity and spatial resolution is an excellent choice as a detector
      in photon fields with high dose gradients such as brachytherapy and radiosurgery.

PMID- 7643794
TI  - A study of the effect of cone shielding in intraoperative radiotherapy.
AB  - The primary goal of intraoperative radiation therapy is to irradiate the
      intraoperatively determined tumor target volume with a single fraction of
      tumoroidal dose while minimizing the dose to all adjacent healthy tissues. To
      reduce dose outside the treatment volume, lead sheets are often used to cover the
      external surface of the cone tip thus providing a shielding for the tissues
      outside the field. In this paper, the effect of the shielding on the depth dose
      distributions and dose profiles at different depths is studied based on
      experimental data. The results were also compared against an EGS4 Monte Carlo
      code for the same geometry as the measurements. The cones varied in size having
      diameters of 5 cm, 7 cm, and 9 cm, and the electron energies ranged from 6 MeV to
      22 MeV. The depth dose curves and dose profiles (at two different depths in the
      phantom) were measured and computed with and without the lead shielding for the
      various combinations of cone sizes and electron energies using a water phantom to
      simulate the patient. It was found that the presence of lead increases on average
      across the treatment area the dose to the tumor from 2% up to 5%, while the dose
      outside the cone was reduced by as much as 75%. Both measurements and
      calculations were found to be in agreement.

PMID- 7643795
TI  - Skin exit dose in megavoltage x-ray beams determined by means of a plane parallel
      ionization chamber (Attix chamber).

PMID- 7643796
TI  - Head phantoms for neutron capture therapy.
AB  - A water-filled head phantom that is designed for use in boron neutron capture
      therapy is described. The shape of this ellipsoidal phantom, based on the Synder
      head model, and its composition are designed to simulate the neutron slowing down
      properties of the human skull and brain. Small ion chambers or activation foils
      can be placed in many locations within the phantom volume. This permits accurate
      three-dimensional mapping of all relevant dose components and use of these dose
      contours for beam development as well as for benchmarking of computer-based
      patient treatment codes.

PMID- 7643797
TI  - The influence of heavy water on boron requirements for neutron capture therapy.
AB  - Neutron penetration in tissue is a major limitation of thermal NCT, as such much
      work has centered upon the epithermal neutron beam in an effort to improve this
      situation. Further gains in neutron flux penetration, and thus therapeutic
      ratios, are possible if natural water is replaced with heavy water prior to
      therapy. Applying MCNP to a heterogeneous ellipsoidal skull/brain model,
      advantage depth and therapeutic depth parameters are studied as a function of
      heavy water replacement for a range of tumor to blood boron ratios. Both thermal
      (0.025 eV) and epithermal (2-7 keV) ideal neutron beams are analyzed. Using 10B
      ratios in the range of documented human uptake, the thermal advantage depth
      improved by approximately 0.7 cm for 20% D2O replacement, however, the
      therapeutic depth increased by less than half this value. For the epithermal
      beam, both the advantage depth and the therapeutic depth increased by over 1 cm.
      Effects of heavy water replacement on 10B requirements to therapeutically treat
      the midline of the brain are also evaluated.

PMID- 7643799
TI  - Directional characteristics of neutrons from the p(66)/Be(40) reaction.

PMID- 7643798
TI  - Physical and biological doses produced from neutron capture in a 235U foil.
AB  - As a follow-on study to the feasibility of neutron capture therapy (NCT) with
      235U brachytherapy seeds, physical doses were calculated and measured for the
      radiation from a 235U foil in a lucite phantom which was irradiated at the
      epithermal neutron irradiation port of the Brookhaven Medical Research Reactor.
      In addition, cell survival experiments were performed to obtain the relative
      biological effectiveness (RBE) for the neutron part of the radiation. The
      calculated absorbed doses agree with the measured ones. From cell survival
      experiments, it is deduced that the fission neutrons from the 235U foil have a
      RBE of 3.0 while the fast neutrons in the beam have a RBE of 3.8. Also observed
      is that, with the cells 7 mm from the foil, a significant amount of absorbed dose
      comes from the beta rays of 235U fission events. This absorbed dose from beta
      rays is a significant addition to the therapeutic dose. Due to the limited ranges
      of beta rays in tissue, this absorbed dose is restricted to the vicinity of the
      foil. This is the first demonstration of beta rays as part of NCT.

PMID- 7643800
TI  - A statistically tailored neural network approach to tomographic image
      reconstruction.
AB  - In previous work it has been shown that a standard backpropagation neural network
      can be trained to reconstruct sections of single photon emission computed
      tomography (SPECT) images based on the planar image projections as inputs. In
      this study, it is demonstrated that an artificial neural network (ANN) trained on
      a series of simulated SPECT images or trained on a set of rudimentary geometric
      images can learn the planar data-to-tomographic image relationship for 64 x 64
      tomograms. As a result, a properly trained ANN can produce accurate, novel image
      reconstructions but without the high computational cost inherent in some
      traditional reconstruction techniques. We also present a method of deriving
      activation functions for a backpropagation ANN that make it readily trainable for
      cardiac SPECT image reconstruction. The activation functions are derived from the
      estimated probability density functions (p.d.f.s) of the ANN training set data.
      The performance of the statistically tailored ANNs are compared with the
      performance of standard sigmoidal back-propagation ANNs, both in terms of their
      trainability and generalization ability. The results presented demonstrate that
      statistically tailored ANNs are significantly better than standard sigmoidal ANNs
      at reconstructing novel tomographic images based on a simulated SPECT image
      training set or a rudimentary geometric image training set. Neural network based
      image reconstruction has two potential advantages over conventional
      reconstruction methods. The first advantage is that ANNs can rapidly
      reconstruction tomograms. Secondly, the quality of the reconstructions produced
      are directly correlated to the quality of the images used to train the ANN.

PMID- 7643801
TI  - Characterization of vertebral strength using digital radiographic analysis of
      bone structure.
AB  - Bone mineral densitometry (BMD) is useful in predicting fracture risk, but,
      unfortunately, there is a significant degree of overlap in BMD measurements of
      patients who have a high risk of fracture and patients with a low risk of
      fracture. In this study, a method of characterizing trabecular bone structure in
      digitized radiographs of vertebrae is proposed and assessed. A significant
      correlation between bone "structure" and the compressive strength of vertebral
      bodies was found. The utility of the parameter for distinguishing between "weak"
      and "strong" bone samples was assessed using receiver operating characteristic
      (ROC) analysis. Using this analysis, the structural parameter produced an area
      under the ROC of 0.88 +/- 0.05, while a bone density measure produced an area of
      0.79 +/- 0.07. The results suggest that the addition of a measure of bone
      structure to the conventional measures of bone density may prove useful in
      predicting the quality of bone when considering surgical or medical intervention
      for osteoporotic conditions.

PMID- 7643802
TI  - Image feature analysis for computer-aided diagnosis: accurate determination of
      ribcage boundary in chest radiographs.
AB  - A computerized method for accurate determination of the ribcage boundary in chest
      images has been developed for use in computer-aided diagnosis (CAD) schemes for
      automated detection of abnormalities such as the pulmonary lung nodules,
      pneumothorax, interstitial disease, cardiomegaly, and interval changes in
      clinical chest images. With our method, the average position of the top of the
      lung in the chest image is determined first. Top lung edges and ribcage edges are
      determined within search ROIs, which are selected over top lung cages and
      ribcages. Three polynomial functions are applied separately to yield smooth
      curves for top lung edges and right and left ribcage edges. The complete ribcage
      boundary is then obtained by smoothly connecting three curves. A total of 1000
      radiographs were digitized to 1k x 1k matrix size and a 10-bit gray scale with a
      laser scanner and analyzed by our method. The subjective evaluation indicated
      that our method produced moderately to highly accurate results in approximately
      96% of the 1000 cases examined.

PMID- 7643803
TI  - Effects of induced charge in the kinestatic charge detector.
AB  - The principle of the kinestatic charge detector (KCD) for digital radiography
      depends on the synchronization of the scan velocity of a parallel plate drift
      chamber with the cation drift velocity. Compared with line-beam scanners, this
      motion-compensated imaging technique makes better use of the x-ray tube output. A
      Frisch grid traditionally has been used within the KCD to minimize unwanted
      signal contributions from both cations and negative charge carriers during
      irradiation. In this work the charge induction process in a parallel plate
      geometry was investigated for the special case of the KCD. In the limit of
      infinite plates, the cathode charge density due to both cations and negative
      charge carriers increases quadratically in time for a kinestatically scanned
      narrow slit. In the KCD the cathode is segmented into an array of narrow
      electrodes, each aligned with the incident x-ray beam. Our conformal mapping
      computation determined that the shape of the induced charge signal depends
      critically on delta x/w, the ratio of electrode width to drift gap. Our
      conclusion introduces the possibility of eliminating the Frisch grid from the KCD
      design because the value of delta x/w required for transverse sampling in the KCD
      is sufficiently low as to allow "self-gridding" to take effect.

PMID- 7643804
TI  - Tests for evaluating laser film digitizers.
AB  - A number of tests to evaluate the image transfer characteristics of laser film
      digitizers have been developed and these tests have been used to evaluate the
      performance of a Konica KFDR-S laser film digitizer. These tests were designed to
      be simple in nature and to use materials readily available in clinical
      departments. The tests examined (i) the geometric accuracy of the laser film
      digitizer; (ii) the linearity of the digitizer's characteristic curve; (iii) the
      temporal/spatial response of the digitizer to abrupt changes in optical density;
      and (iv) the noise added by the digitizer to the digitized images. The tests were
      easy to use and could be performed in a short period of time. Results of the
      tests for the Konica laser film digitizer revealed several problems including
      minor geometric inaccuracies, structural noise added by a shading correction
      circuit in the digitizer, and spread of the laser beam before reaching the film
      plane, possibly caused by the f-theta lens of the digitizer. The light spread
      made the optical density of small, high density structures measured by the
      digitizer dependent upon the optical density of the surrounding regions.
      Therefore, under some circumstances, film digitization with the Konica laser film
      digitizer could lead to erroneous results. In addition, our measurements suggest
      that these problems are not unique to the Konica digitizer. Thus, the testing of
      laser film digitizers is recommended, especially if the digitizer is to be used
      for quantitative measurements.

PMID- 7643805
TI  - Comparison of receiver operating characteristic and forced choice observer
      performance measurement methods.
AB  - The receiver operating characteristic (ROC) method has been successfully used in
      medical imaging for 20 years. It has been so successful that many people think of
      it as an end in itself rather than just one of several ways to assess human
      observer performance of image based decision tasks. Studies of human and ideal
      observer decision performance are designed to estimate a measure of observer
      performance (e.g., efficiency, d' or da). The experimenter would like to obtain
      accurate and precise estimates using a relatively small number of images or
      decision trials because of a variety of constraints. One purpose of this paper is
      to introduce medical physicists to another effective psychophysical measurement
      technique, the forced choice method. The second purpose is to present a
      comparison of the forced choice and ROC methods, with particular attention to
      sampling statistics considerations. In brief, the rating scale ROC method is
      preferable when the limiting constraint is the number of images and at the same
      time it is not feasible to use the forced choice with more than four
      alternatives. The forced choice method can be superior for experiments using
      synthetic images, under some conditions.

PMID- 7643806
TI  - Comparison of body weight, body height and body fatness of Italian children aged
      6-12 years with American standards.
AB  - World Health Organization has suggested that American standards may be adopted
      for use in countries where no local reference data are available. Since no
      locally accepted growth standard is available in Italy, this study investigated
      if American growth curves for weight, height and triceps skinfold (TSF) provide
      reliable values for Italian children. Weight, height and TSF were measured in
      1273 Italian children (boys: 656, girls: 617) ranging in age from 6 to 12 years
      and their percentiles were compared with that provided by NCHS for American
      children. Despite some minor differences, it is shown that American standards can
      be used safely in Italian children aged from 6 to 12 years.

PMID- 7643807
TI  - [Echographic and sonographic study of ovaries in girls with precocious puberty].
AB  - The aim of this study is the biometrical and morphological evaluation of the
      ovaries by sonography and the study of the haemodynamics of the ovarian artery
      flow by doppler ultrasound in 14 girls with precocious puberty and in 33 control
      subjects. All people ranged in age from 5 to 7 years. The gonadian mean volume
      and the mean pulsatility index have been evaluated. A significant difference in
      the ovarian volume has been found between patients and controls. No index between
      the two groups. We conclude that the doppler ultrasound needs a larger number of
      cases to evaluate its validity in girls with precocious puberty.

PMID- 7643808
TI  - [Tuberous sclerosis: neuropsychological implications].
AB  - The role of neurosurgical therapy in tuberous sclerosis is still controversial;
      generally, a surgical procedure is performed only to treat an increase in
      intracranial pressure secondary to an obstructive hydrocephalus caused by a
      neoplasm in the region of the foramen of Monro. The role of surgical treatment in
      the control of epileptic fits is much more limited because of multifocal EEG
      epileptogenic foci due to multiple cortical lesions. Recently some authors,
      however, have suggested that the surgical treatment may be useful in selected
      patients. In the present report 9 children affected by tuberous sclerosis who
      were operated on in the period 1982-1992, because of increased intracranial
      pressure are described. The neuroradiological examination showed tumors in the
      region of the foramen of Monro in all the patients, with secondary obstruction in
      the CSF shunt circulation. Operative procedures included CSF shunts and/or giant
      cell astrocytoma removal. The follow-up period ranged from 1 to 14 years (mean 6
      years). According to our experience, tumor excision is the most satisfying
      therapy, allowing the removal of the cause of the hydrocephalus as well as the
      possibility of histological diagnosis. A CSF shunt procedure may resolve the
      symptomatology, but it is often weighted by frequent malfunctioning of the CSF
      shunt system due to catheter obstruction secondary to abnormally high CSF protein
      concentration; furthermore, in some patients the insertion of the ventricular
      catheter may induce intraventricular bleeding when the highly vascularized tumor
      is accidentally punctured during the procedure of shunt insertion or in cases in
      which the presence of the ventricular catheter causes chronic trauma on the
      tumoral surface.

PMID- 7643809
TI  - [Assessment of lead blood levels in children living in Lucca (Italy) in 1993. The
      study was conducted as part of the project METOS, in accordance with the decree
      496 of June 1982 which adopted the directive CEE No.77/312].
AB  - OBJECTIVE: Lead poisoning is a major cause of environmental concern in all
      countries worldwide. Saturnism in children, especially if young and neglected,
      represents a peculiar phenomenon both in terms of the biology of growing subjects
      and the epidemiological nature of poisoning. In under five-year-olds, in addition
      to lead levels in the atmosphere, it is equally important to evaluate the
      presence of contaminated dust in the house, hand-to-mouth activities and the
      level of care provided by parents. It has been demonstrated that, in the presence
      of equivalent environmental lead levels, dust removal from the house and
      prevention of hand-to-mouth activities can successfully reduce lead blood levels
      (PbB) in children. AIM: The aim of this study was to evaluate the risk of chronic
      lead poisoning in children attending Local Health Unit 6 in Piana di Lucca and to
      assess the need for a possible health education campaign aimed at eliminating the
      specific pediatric risk for lead poisoning. MATERIALS AND METHODS: Assay of lead
      blood levels in 172 children from 0 to 14 years old consecutively attending the
      Emergency Ward at Campo di Marte Hospital in Lucca for reasons not relating to
      lead poisoning. RESULTS: Mean lead blood levels in children were 57.2 +/- 30.2
      mg/l (mean 50 mg/l) without significant differences between the various age
      brackets (0-5, 6-10, 11-14 years old). Only one child presented pathological PbB
      levels (280 mg/l when first measured; 360 mg/l a few months later with normal
      values of erythrocytic Zn-protoporphyrin, 24-h urinary lead excretion and 24-h
      urinary delta-aminolevulinic acid). An epidemiological study is now being made of
      the causes. The general population within the same area presented mean PbB levels
      of 70.4 +/- 36.9 mg/l (mean 60 mg/l), measured in a total of 471 subjects (adults
      and children). DISCUSSION AND CONCLUSIONS: The PbB levels currently found in
      children resident in Lucca confirm a low-risk environmental situation. Preventive
      measures specifically aimed at children do not therefore appear to be justified
      at present.

PMID- 7643810
TI  - [Wolfram syndrome. Personal experience].
AB  - We report on a young patient who suffered from diabetes mellitus and
      neurosensorial deafness from the age of two. One year later she was noted to have
      deteriorated vision and the diagnosis of optic atrophy was made, her visual
      acuity decreased progressively. At the age of six she was admitted to our
      hospital because of thiamine responsive megaloblastic anemia, a rare clinical
      feature of Wolfram's syndrome (only 13 cases have been reported to date).
      Thiamine (75 mg/day) was commenced at a single oral dose with a rapid increase of
      Hb level after a few days of therapy. The insulin requirement didn't decrease
      during thiamine therapy, the C-peptide level after glucagon remained almost
      indosable. No improvement was observed in the deafness and in the optic atrophy.
      These findings suggest that diabetes mellitus and optic atrophy, in Wolfram's
      syndrome are not related to thiamine metabolism.

PMID- 7643811
TI  - [Crossed renal ectopy with fusion. Report of a case].
AB  - Crossed renal ectopia is a rare urinary tract anomaly, often associated with
      malformations involving various organs and systems. We report a case of crossed
      renal ectopy with fusion, without associated abnormalities. Recurrent abdominal
      pain, sometimes with microhematuria, were the clinical features, never
      accompanied by alteration of the renal function.

PMID- 7643812
TI  - [Osteopetrosis and renal acidosis: a new case of this rare syndrome].
AB  - The association between osteopetrosis and renal acidosis is not accidental, but
      represents a well-known syndrome with autosomal recessive transmission, due to
      carbonic anhydrase II(CA II) deficiency. The disease is extremely rare (only few
      reports in the literature). The diagnosis is confirmed by CA II erythrocyte
      assay. However, this finding is not essential when the clinical picture is
      complete, as in the case reported in this paper, which presents a patient with
      osteopetrosis, proximal tubular acidosis, intracranial calcifications,
      psychomotor retardation and short stature. Prenatal diagnosis will rely on the
      genetic study of DNA by molecular probes, since it is already well-known that the
      coding gene for CA II is on the long arm of chromosome 8 (8q22).

PMID- 7643813
TI  - [Renovascular hypertension-bilateral kidney: autotransplantation and
      reconstruction of the aorta with autologous saphena].
AB  - The authors describe a patient with stenosis of the renal artery undergoing
      bilateral kidney autotransplantation and reconstruction of the aorta with
      autologous saphena. This study also provides a general evaluation of renovascular
      hypertension incidence, etiopathogenesis, symptomatology, diagnostic criteria,
      therapy. The presence of a diastolic pressure > 110 mmHg, with normal creatinin
      levels and urinalysis results, is very significant and leads to invasive
      investigations. Site and size of the anatomic anomaly are evaluated by
      arteriography. Surgery is the treatment of choice.

PMID- 7643815
TI  - [Early infantile autism: a new hypothesis].

PMID- 7643814
TI  - [Treatment of metastatic osteosarcoma with verapamil, cyclosporine and
      chemotherapy. A case report].
AB  - Studies on the use of revertants to overcome MDR have aroused a great interest
      even if they failed to prove their actual usefulness. A case of 10 years and 6
      months old boy is described. He suffered from osteoblastic osteosarcoma and
      underwent chemotherapy following CNR-NEO3 protocol, wide surgical resection and
      postoperative chemotherapy. Nineteen months after diagnosis he underwent the
      removal of a little subpleural nodule in the right lung. Forty-five days later,
      in the same site, a large local metastasis was observed together with many others
      secondaries localizations spred in both lungs. Because of the rapid evolution
      they were considered not suitable for surgical treatment. A cyclosporine and
      verapamil treatment in association with adryamicin and etoposide was begun with
      the aim overcoming multidrug resistance. Five treatments were provided. ECG
      monitoring during verapamil infusion did not show any trouble; mielotoxicity was
      mild, with no need of transfusions. A lung CT scan at the end of the therapy
      demonstrated an important decrease of the subpleural metastasis and the vanishing
      of lung nodules. Another surgical intervention was provided together with 2
      postoperative chemotherapy treatments. Twenty-six months later no sign of the
      disease was observed. Association of verapamil and cyclosporine with chemotherapy
      allowed to get a good clinical response with a very low toxicity, in a critical
      situation in which chemotherapy alone did not seem to offer any real possibility.

PMID- 7643816
TI  - [Food allergy: comparison of diagnostic techniques].
AB  - Fourteen children affected with allergic disease, from 8 months to 7-years-old,
      were studied; three children had Bronchial asthma, one child Bronchial asthma and
      rhinitis, one child recurrent laryngospasm, six children atopic dermatitis, two
      children diarrhoea, one abdominal pain. In all patients cow's milk and egg were
      the most common offending foods. Total IgE serum level, IgE serum specific, Prick
      test and ALCAT test (the test predicts food which would produce a problem) were
      investigated. A comparison among the different laboratory methods for food
      allergy diagnosis was analyzed.

PMID- 7643817
TI  - [Abdominal pain and defecation disorders without a known organic origin:
      importance of the psychodiagnosis].
AB  - The authors submitted some children examined in the Division of Pediatric Surgery
      of the Ospedali Galliera in Genoa to a psychodiagnostic evaluation. They
      presented abdominal pain and defecation disorders, whose organic etiology was not
      demonstrated. The psychodiagnostic evaluation, consisting in colloquia, tests,
      drawings and plays, was completed in 11 of the 28 patients referred. A profoundly
      disturbed and protagonist mother-child relationship and a frequent "border
      position" of the father was focused. The symptoms disappeared in 8 of the 11
      patients during the diagnostic evaluation, that resulted, its own, therapeutic. 3
      patients were treated with psychotherapy and a remarkable improvement at 6 months
      from the beginning of therapy was noticed. Seventeen patients were lost because
      they didn't come to the outpatient dates or because they were already followed by
      other specialists in their residential zones. The authors believe that a
      psychodiagnostic evaluation is important in children with abdominal pain and
      defecation disorders whose organic origin has not been demonstrated.

PMID- 7643818
TI  - [Diagnostic considerations on sinusitis in childhood].
AB  - The presence of a radiographic sinusal opacification without any other clinical
      sign or symptom cannot lead to the diagnosis of "Sinusitis", if considered alone.
      In a previous paper we observed a high prevalence of patients with both clinical
      and radiographic signs of sinusitis and a high prevalence of neutrophils in the
      nasal secretions, now we tried to discover which clinical signs and symptoms are
      more likely to indicate an acute sinusitis. We compared cough, headache,
      bacteriological culture of nasal secretions with a sinusal CT scan, without
      finding any relationship. On the contrary, neutrophils in the nasal secretions
      and Rx are strictly inter-related with CT scan, with a sensitivity of 77% and a
      specificity of 100%.

PMID- 7643819
TI  - [Pseudomonas aeruginosa colonization in Turin CF center. Microbiological and
      therapeutic observations].
AB  - We reviewed 4,277 sputum cultures performed in our FC patients during
      antipseudomonas courses of antibiotic therapy. The median age of colonization is
      8.6 years, and the chronically infected subjects are 33.65% of all our patients.
      The most efficient antibiotics were imipenem, aztreonam, ceftazidime and
      amikacin. Ceftazidime gave the best results in terms of antibiotic resistance.

PMID- 7643820
TI  - [Psychopathological risk in children with early onset of partial epilepsy].
AB  - In this study we compare the peculiarities of psychopathological risk in children
      with partial epilepsy versus children with chronic illness. Sixteen children
      affected by epilepsy with partial seizures, symptomatic or cryptogenetic (group
      A), are compared with 16 children affected by diabetes mellitus type 1 (group B)
      and with 16 early treated congenital hypothyroid children (group C). For the
      valuation we have used: 1) Rutter scales for parents; 2) questionnaire on
      maternal attitude towards epilepsy, modified for diabetes and hypothyroid
      children; 3) anamnestic interviews for epileptic patients; 4) individual
      observations. We have emphasized that: 1) the quality of life in children with
      epilepsy and their families is poorer compared to the ones of the other
      chronically ill children; 2) the attack is the most characterising factor of life
      quality of both group A and group B; 3) both group A and group B show an
      important anxiety for cognitive and behavioural disturbances; 4) in epilepsy
      families several factors contribute to the increased anxiety towards social life:
      occurrence of seizures, side effects of drugs, real or supposed underlying
      encephalopathy.

PMID- 7643821
TI  - [Effects of various dosage of ketoprofen salt suppositories in acute inflammatory
      disease in infants (3-36 month old) and children (3-13 year old)].
AB  - In two multicentric randomized, double-blind, parallel design trials the more
      appropriate dose of ketoprofen lysine salt suppositories, by considering benefit
      risk ratio, was determined in children affected by acute inflammatory disease of
      respiratory or urinary tract with fever and pain. Fifty-three children ranging 6
      36 months (infants) randomly assigned to 20, 30, 40 mg dose levels, and 54
      children ranging 3-13 years (children) randomly assigned to 40, 60, 80 mg dose
      levels were included in the studies. Efficacy variables considered were
      hyperthermia and pain; body temperature was measured rectally, at fixed intervals
      and pain was evaluated by Maunuskela scale at the same interval times. Standard
      laboratory test were obtained at the beginning and end of treatment, and blood
      arterial pressure and heart rate were recorded regularly. Systemic and local
      tolerability were also determined. In infants all doses were associated with
      analgesia and temperature reduction; antipyretic effect was statistically
      significant starting from the first hour (p = 0.007). The dose of 30 mg resulted
      different from 20 mg dose from third hour (p < 0.05). The appropriate dose that
      better relate antipyretic and analgesic efficacy with a good tolerability was 30
      mg. In children the analgesic and antipyretic efficacy was well established at
      all doses tested, however the effects were more marked and prolonged at 60 and 80
      mg doses, with a better tolerability for 60 mg dose. The tolerability of all
      doses studied was good. Doses of 30 mg in infants and 60 mg in children
      correspond to a range of 2.0-3.5 mg of ketoprofen lysine salt for kg body weight,
      for each administration.

PMID- 7643822
TI  - The borderland between neurology and history. Conversion reactions.
AB  - The epidemic of conversion reactions taking place at the end of the twentieth
      century is a result of long-term changes in the presentation of functional
      illness. These changes often are a response to deeper issues in the culture about
      what constitutes legitimate organic disease. This epidemic also is a response to
      short-term changes in the attributions to which patients ascribe their illnesses.
      Such attributions are heavily influenced by the media, and clinicians must be on
      guard against both long- and short-term changes as they affect the presentation
      and attribution of illness.

PMID- 7643824
TI  - The detection of deception.
AB  - In clinical situations patient honesty and self-interest usually coincide;
      however, in legal circumstances patients may be motivated to deceive and may be
      skilled in doing so. Research raises doubts about the capacity of health
      professionals to detect malingering, particularly when there is less known about
      conditions or expected symptom patterns, more definitive tests are lacking or
      require patient cooperation, and diagnosis depends substantially on patient self
      report. Given the lack of systematic feedback about our judgmental accuracy when
      deciding the presence or absence of malingering, clinical experience per se
      provides an inadequate means for identifying and correcting erroneous practices
      and for determining just how confident we ought to be in our subjective
      impressions. Thus, in the appraisal of malingering, it is dangerous to place too
      much dependence on subjective confidence. Methods are discussed that can
      supplement medical examination and increase the accuracy of malingering
      detection.

PMID- 7643823
TI  - Dimensions of somatization and hypochondriasis.
AB  - A significantly large group of patients who communicate their psychosocial
      distress in the form of physical symptoms are called somatizers. They tend to
      overuse medical services. The syndromes with which they present have indistinct
      boundaries, and there tends to be some fluidity of their symptomatic
      presentations. Underlying psychiatric disorders such as mood disorders, anxiety
      disorders (including obsessive compulsive disorder), and personality disorders
      are frequently present.

PMID- 7643825
TI  - Munchausen's syndrome and other factitious disorders.
AB  - Factitious disorders including Munchausen's syndrome are likely encountered by
      all clinicians during their career. Neurologic presentations are common,
      especially with Munchausen's syndrome by proxy. An appropriate index of suspicion
      and nonjudgemental confrontation and psychiatric consultation facilitate a
      successful clinical approach. Redefining the factitious illness as psychiatric
      with continued involvement of a primary physician and family support are also
      keys to successful management. Underlying psychiatric syndromes need to be
      assiduously evaluated and steadfastly treated. Prognosis is best for patients who
      do not meet criteria for Munchausen's syndrome or who have psychosocial supports
      and less severe personality pathology.

PMID- 7643826
TI  - Psychogenic movement disorders.
AB  - The diagnosis of PMDs is by no means a simple task. Organic movement disorders
      are more often misdiagnosed as psychogenic rather than the reverse. The degree to
      which psychological factors underlie movement disorders may range from being the
      exclusive cause to being a reaction to the movement disorder. The most common
      psychiatric illnesses associated with PMDs are depression, conversion reactions,
      and anxiety disorders. Although the diagnosis of psychogenicity may seem elusive,
      the definitions and diagnostic criteria of PMDs outlined in this article serve as
      useful guidelines for obtaining a more accurate diagnosis. The emphasis on a
      multidisciplinary approach with a strong alliance of neurologist and psychologist
      or psychiatrist is essential to assure proper diagnoses and treatment.

PMID- 7643827
TI  - Nonepileptic seizures.
AB  - The widespread use of video-electroencephalogram monitoring has dramatically
      increased our recognition of the high prevalence and diversity of nonepileptic
      seizures. Nonepileptic seizures stand squarely in the interface between
      psychiatry and neurology, an area that has been both claimed and denied by both
      sides. Collaborative exploration of this border zone has provided new insights
      into a disorder that may be as ancient as epilepsy.

PMID- 7643828
TI  - Neuro-ophthalmologic presentations of functional visual disorders.
AB  - Functional or nonorganic visual loss is a common problem that requires an active
      diagnosis. A complete neuro-ophthalmologic examination of the afferent and
      efferent visual system is essential to eliminate the possibility of organic
      causes of visual loss. With a sound knowledge of the anatomic, physiologic, and
      optical basis of the tests used to evaluate the visual pathway, the physician can
      detect the inconsistencies in visual performance that secure the diagnosis. The
      majority of patients will resolve their symptoms with time and reassurance.

PMID- 7643829
TI  - Chronic pain in litigation. What is the relationship?
AB  - The legal system is often as random and capricious as the very accident itself.
      The present tort system is fault-based and is vulnerable to the pressures of
      lawyers and patients who exploit subjective symptomatology for primary and
      secondary gain. Jury awards for noneconomic damages have little consistency and
      have produced astronomic awards for subjective pain and suffering. The surge in
      fraudulent claims exposes the weaknesses of the current system. This article is
      not intended to convey the notion that all cases of CPS in litigation are
      fraudulent, but rather suggests that unraveling this association is a formidable
      task that must be done owing to the huge economic burden to society. Prospective
      studies are urgently needed to more accurately define the natural history of
      individuals with CPS in litigation.

PMID- 7643830
TI  - Reflex sympathetic dystrophy. A common clinical avenue for somatoform expression.
AB  - Reflex sympathetic dystrophy (RSD) and causalgia appear to reflect identical
      pictures even though the latter is related to nerve injury and the former is not.
      Overriding past and present skepticism about a role for the sympathetic system in
      their cause and treatment, the International Association for the Study of Pain
      still recommends sympathetic blocks and sympathectomy for both causalgia and RSD.
      Such fallacy is traceable to fragmentary clinical observations, to ad-hoc
      experiments, and to traditional neglect of the placebo phenomenon in chronic
      "neuropathic" pain patients.

PMID- 7643831
TI  - Fibromyalgia syndrome and myofascial pain syndrome. Do they exist?
AB  - "It is in the healing business that the temptations of junk science are the
      strongest and the controls against it the weakest." Despite their subjective
      nature, these syndromes (particularly MPS) have little reliability and validity,
      and advocates paint them as "objective." Despite a legacy of poor-quality
      science, enthusiasts continue to cite small, methodologically flawed studies
      purporting to show biologic variables for these syndromes. Despite a wealth of
      traditional pain research, disciples continue to ignore the placebo effect,
      demonstrating a therapeutic hubris despite studies showing a dismal natural
      history for FS. In reviewing the literature on MPS and FS, F.M.R. Walshe's sage
      words come to mind that the advocates of these syndromes are "better armed with
      technique than with judgment." A sympathic observer might claim that labeling
      patients with monikers of nondiseases such as FS and MPS may not be such a bad
      thing. After all, there is still a stigma for psychiatric disease in our society,
      and even telling a sufferer that this plays only a partial role may put that
      patient on the defensive. Labeling may have iatrogenic consequences, however,
      particularly in the setting of the work place. Furthermore, review of a typical
      support group newsletter gives ipso facto proof of this noxious potential. The
      author of a flyer stuffed inside the newsletter complains that getting social
      security and disability benefits for "the invisible disability" can be "an uphill
      battle. But don't loose (sic) hope." Apparently the "seriousness of the
      condition" is not appreciated by the medical community at large, and "clinician
      bias may well be the largest threat," according to Boston epidemiologist Dr. John
      Mason. Sufferers are urged to trek to their local medical library and pull four
      particular articles claiming FS patients have more "stress," "daily hassles," and
      difficulty working compared with arthritis patients. If articles can't be
      located, patients are told to ask their lawyers for help. Although "Chronic
      Fatigue Syndrome" and FS are not considered by everyone to be the same malady,
      the "National Institute of Health (sic) has lumped these two conditions together.
      This could work in your favor." (A U.S. political advocacy packet is available
      for $8, but a list of U.S. senators with Washington, DC addresses is freely
      provided.) These persons see themselves as victims worthy of a star appearance on
      the Oprah Winfrey show. A sense of bitterness emerges; one literally bed-bound
      Texas homemaker writes in Parents magazine that "Some doctors may give up and
      tell you that you are a hypochondriac."(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7643832
TI  - The electrodiagnostic examination with hysteria-conversion reaction and
      malingering.
AB  - Electrodiagnostic examination (EDX) can be helpful in assessing patients with
      hysteria-conversion reaction (H-CR) and malingering. The EDX with both H-CR and
      malingering are identical, but the electromyographer usually distinguishes one
      from another based on how the patient responds to the situation. EDX not only can
      demonstrate that symptoms are probably nonorganic in nature, but also can show
      that symptoms attributed clinically to H-CR and malingering actually have an
      organic basis.

PMID- 7643833
TI  - The sick building syndrome and mass hysteria.
AB  - Significant overlaps of symptoms in SBS and MH exist including central nervous
      system manifestations, mucous membrane irritation, skin abnormalities, and eye
      symptomatology. Both occur with greater frequency in women with lower job rank
      and in patients with psychological and physical stresses. No specific cause has
      been identified in over 75% of the cases of SBS. Remotely, less than 25% have
      been alleged to be secondary to an environmental toxin but even removal of the
      inciting irritant does not improve the symptoms. Not surprisingly, litigation is
      lurking in the background with the chronic complainer. There has been no evidence
      of exposure to toxins or VOCs that exceed the NIOSH safety standards in any SBS
      cases. The importance of a thorough work up is to distinguish those cases that
      are secondary to bacteria or toxic contaminants and infection where significant
      morbidity and death have occurred in the building related illness. Although this
      is a separate entity it indicates that the building environment can be a
      significant cause of morbidity and mortality. Other variables such as temperature
      and humidity do influence the frequency of SBS symptomatology. It may be that we
      are not yet sophisticated enough to find the causes that are present within our
      current paradigms. Current levels of toxic data testing may not be sensitive
      enough to realize that they might be a cause of toxicity. It might be that at low
      levels with multiple toxins and VOCs present, the additive effects may cause
      toxic symptomatology whereas individually they do not. In summary, SBS is an
      emerging phenomena within our litigious society.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7643834
TI  - Post-traumatic stress disorder. Does it exist?
AB  - Facing the inevitable, psychiatry formally acquired PTSD as a diagnostic entity
      in 1980. It then discovered that PTSD had a bevy of nasty laylegal relatives
      (e.g., disability and personal injury claims). In response, psychiatrists have
      been continuously trying to refine PTSD criteria. There have even been cogent
      arguments that psychiatrists should take their own forensic medicine and formally
      address legally relevant behavior in the DSM. In the meantime, prosecutors,
      defense attorneys, and adjudicators sometimes stretch and pull the DSM-III-R PTSD
      diagnosis beyond justifiable limits to try to fit square pegs of psychiatric
      testimony into round holes of legal rules. Ultimately, however, lawyers cannot be
      blamed for misusing the PTSD diagnosis because only clinicians can make it.
      Causal diagnosticians may fail to apply the requisite symptomatic criteria or do
      so only superficially. In their haste to eliminate bogus stress claims,
      clinicians should not throw out the baby (authentic PTSD) with the bathwater
      (idiosyncratic "stress" disorders and careless PTSD diagnoses).

PMID- 7643835
TI  - Occupational injury. Fact, fantasy, or fraud?
AB  - The preceding describes some of the confusion which abounds in practically all
      areas of clinical medicine and particularly in occupational injuries. In essence,
      this confusion devolves to a primary failure on our part as clinicians; the
      failure to differentiate fact from fantasy. In the clinical arena, this is the
      failure to differentiate between that which is clinical pathology in the
      peripheral neuromusculoskeletal system and that which is no less real for the
      patient, a fantasy arising from image-driven, adaptively-initiated activation of
      specific neuronal groups in the somatosensory or somatomotor cortex,
      descriptively referred to as "hysterical" or "psychogenic." A common experience
      of neurologists and other clinicians conducting a sensory examination of the
      extremities is the presence of nondermatomal or glovelike sensory changes of the
      feet or hands. Nondermatomal sensory changes are known to engage any part of the
      body surface. These have often been referred to as hysterical; however, in the
      clinical sensory examination for touch, vibration, and pinprick, the patient has
      no control over the area or boundaries of the activated receptive fields in the
      somatosensory cortex. Fantasies of the patient, provoked by the context of
      examination, initiate an adaptive response which can expand or contract the
      boundaries of the somatosensory receptive fields. These sensory changes are
      unconscious and represent alteration of receptive fields in the somatosensory
      cortex. The brain is re-entrantly connected. Activation in one area promotes
      activation in adjacent and associated areas remote from the primary receptive
      field. The brain organizes its own activity. "Perception thus is not imposed on
      the brain; rather the brain selects the perceptual mode.... stimulus energy,
      according to numerous studies from brain-activation, is only a weak determinant
      of the magnitude of response in primary sensory areas. . . ." The most intense
      brain activation in the somatosensory cortex is provoked, not by peripheral
      stimulation, but by adaptive preparation referred to as somatotopical tuning,
      probably due to an increase in excitatory post-synaptic potentials (EPSPs). Many
      patients present to neurologists and other clinicians with complaints of numbness
      and tingling in the fingers, hands, arms, or face and occasionally, as in one of
      my patients, the entire body.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7643836
TI  - "On spitballs and bubbles".

PMID- 7643837
TI  - Managed care disrupts the patient-physician relationship.

PMID- 7643838
TI  - Otolaryngology quiz #5. Left ear cholesteatoma.

PMID- 7643839
TI  - The role of the physician in the dynamics of change under managed care.

PMID- 7643840
TI  - Can American democracy and the profession of medicine survive the giant managed
      care oligopolies? Justice Louis D. Brandeis and "The Curse of Bigness".

PMID- 7643841
TI  - Valproic toxicity with fluoxetine therapy.

PMID- 7643843
TI  - A comparison of the restraint and seclusion experiences of patients with
      schizophrenia or other psychotic disorders.
AB  - OBJECTIVE: The purpose of this study was to understand how restrained and
      secluded patients felt about these interventions, and to compare the perceptions
      of the two groups. METHODS: Subjects were 25 restrained, and 25 secluded
      inpatients. A questionnaire was developed to explore patients' feelings and
      perceptions of the two interventions. Comparisons were made on the clinical data
      and the answers from both groups. RESULTS: Restrained and secluded patients
      seemed to view some aspects of their experience differently. Few (40%) of the
      secluded group reported finding positive aspects, compared to even fewer (20%) of
      restrained. Most patients in both groups felt negatively about staff involved,
      and disagreed with staff on the reported intensity of their documented
      threatening behavior. The interventions seemed to have only a brief modifying
      effect on patients' behavior following these interventions and did not seem to
      modify future behavior. CONCLUSIONS: Despite their differences, many patients in
      both groups reported negative feelings about the interventions and the staff
      involved. Both groups seemed not to perceive the procedural staff interactions as
      communication. Our study population seemed to be a subgroup of the admitted
      patient population who were repeatedly requiring seclusion or restraint.
      Screening this patient population during the admission process, and planning
      preventive and alternative interventions could decrease the need for restraint
      and seclusion.

PMID- 7643842
TI  - Rare primary signet ring carcinoma of the pancreas.
AB  - Signet ring carcinoma of the pancreas is a rare mucin-producing variant occurring
      in less than 1% of pancreatic carcinoma. The fourth leading cause of cancer
      deaths in the U.S., pancreatic carcinoma is increasing in incidence and
      mortality. It is difficult to detect during the early stages of the disease and
      usually become apparent when extrahepatic biliary obstruction occurs. Early
      radiologic findings may be negative and there is no well defined tumor marker for
      this neoplasm.

PMID- 7643844
TI  - The experience of infertility among women who have sought treatment.

PMID- 7643845
TI  - "Patient-focused care" and other incantations.

PMID- 7643846
TI  - Nursing without nurses--the new twist in health care reform.

PMID- 7643847
TI  - Human rabies--Washington, 1995.
AB  - On March 15, 1995, a 4-year-old girl who resided in Lewis County, Washington,
      died from rabies. This report summarizes the clinical course, epidemiologic
      investigation, and probable exposure history of the case.

PMID- 7643848
TI  - Blood lead levels among children in a managed-care organization--California,
      October 1992-March 1993.
AB  - Despite substantial progress in reducing exposures to lead among children, as
      recently as 1991, 9% of children in the United States had blood lead levels
      (BLLs) of > or = 10 micrograms/dL (1)--levels that can adversely affect
      intelligence and behavior. In 1991, CDC recommended screening all children for
      lead exposure except those residing in communities in which large numbers or
      percentages previously had been screened and determined not to have lead
      poisoning (2). Subsequently, the California Department of Health Services (CDHS)
      issued a directive to all California health-care providers participating in the
      Child Health and Disability Prevention Program to routinely screen children for
      lead poisoning in accordance with the 1991 CDC guidelines (3). This report
      presents finding of BLL testing during 1992-1993 from a managed-care organization
      that provides primary-care services to Medicaid beneficiaries in several
      locations in California (i.e., Los Angeles County, Orange County, San Bernardino
      County, Riverside County, Sacramento, and Placerville).

PMID- 7643849
TI  - Hypertension among Mexican Americans--United States, 1982-1984 and 1988-1991.
AB  - Since 1960, data have been collected on measured blood pressure for non-Hispanic
      whites and blacks. However, few data have been available measured blood pressure
      for Mexican Americans (1). Until the release of data from the National Health and
      Nutrition Examination III, Phase I (NHANES III), the only source of blood
      pressure data for most of the Mexican American population in the United States
      was the Hispanic Health and Nutrition Examination Survey (HHANES). Data on
      measured blood pressure for other Hispanic subgroups (i.e., Cuban Americans and
      Puerto Ricans) were available in HHANES but not in NHANES III. To identify trends
      in prevalence, awareness, treatment, and control of hypertension among Mexican
      Americans aged 18-74 years, HHANES (conducted during 1982-1984) and NHANES III
      (conducted during 1988-1991) were analyzed. This report summarizes the results of
      that analysis.

PMID- 7643850
TI  - Arboviral disease--United States, 1994.
AB  - Arboviruses are mosquitoborne and tickborne agents that persist in nature in
      complex cycles involving birds and mammals, including humans. Characteristics of
      arboviral infection include fever, headache, encephalitis, and sometimes death.
      In 1994, health departments in 20 states reported 100 presumptive or confirmed
      human cases of arboviral disease to CDC. Of these, 76 were California (CAL)
      serogroup encephalitis; 20, St. Louis encephalitis (SLE); two, western equine
      encephalomyelitis (WEE); one, eastern equine encephalomyelitis (EEE); and one,
      Powassan encephalitis (POW). This report summarizes information about arboviral
      disease in the United States during 1994.

PMID- 7643851
TI  - Update: influenza activity--worldwide, 1995.
AB  - From October 1994 through August 1995, influenza activity occurred at low to
      moderate levels in most parts of the world. Influenza activity usually was
      associated with the cocirculation of influenza types A and B viruses. Overall,
      influenza A(H3N2) was the predominant influenza A subtype, but isolation of
      influenza A(H1N1) viruses increased during this period and was the most
      frequently isolated influenza virus in Australia from March through August. This
      report summarizes influenza activity worldwide from March through August 1995.

PMID- 7643852
TI  - NIOSH alert: request for assistance in preventing deaths and injuries of
      adolescent workers.

PMID- 7643853
TI  - In vitro induction of primary, antigen-specific CTL from human peripheral blood
      mononuclear cells stimulated with synthetic peptides.
AB  - A protocol for in vitro induction of primary, antigen-specific CTL from human
      peripheral blood mononuclear cells (PBMCs) was developed. Antigen presenting
      cells (APCs) consisted of Staphylococcus aureus Cowan-I (SAC-I) activated PBMCs
      treated with a citrate-phosphate buffer at pH 3 to release endogenous peptides
      bound to surface MHC. This treatment resulted in transient expression of empty
      class I molecules which could be subsequently stabilized with peptide and beta 2
      microglobulin (beta 2m). SAC-I activated PBMCs from HLA-A2.1 normal donors loaded
      with HBV core 18-27 peptide following acid treatment were used to stimulate PBMCs
      depleted of CD4+ T cells, in the presence of recombinant interleukin-7 (rIL-7).
      After 12 days, cells were restimulated with autologous, peptide-pulsed, adherent
      cells and tested for CTL activity 7 days later. In 23 independent experiments
      from 13 different HLA-A2.1 donors, this protocol resulted in induction of primary
      CTL more than 90% of the time. As indicated by both the frequency and magnitude
      of the response against peptide-sensitized target cells, SAC-I activated PBMCs
      treated with acid were the most efficient stimulator APC. Thirteen per cent of
      the cultures generated were capable of lysing target cells transfected with the
      HBV core antigen and, in general, these CTL cultures exhibited high avidity for
      the HBV core peptide. This protocol is generally applicable to different antigens
      and class I alleles, and thus, may be utilized to screen large numbers of
      peptides to identify human CTL epitopes.

PMID- 7643854
TI  - Db-binding peptides from influenza virus: effect of non-anchor residues on
      stability and immunodominance.
AB  - Relative affinities were determined for the interaction of H-2Db with all the
      peptides from the A/PR/8/34 strain of influenza virus that contained the Db
      binding motif. The results indicated that, even though 23 peptides with the
      appropriate motif were identified and analysed, binding of only five of them
      could be detected at peptide concentrations lower than 10(-7) M. Of these five,
      only one, TGICNQNII, bound with better affinity than the nucleoprotein-derived
      natural epitope, ASNENMETM. The origin of the higher binding peptide was the
      influenza neuraminidase, a protein for which little cytosolic processing would be
      expected since it is a surface glycoprotein. To establish why many of the
      influenza-derived peptides did not bind, the role of non-anchor residues on Db
      peptide interactions was analysed, using a scheme where QDIENEEKI, a non-binding
      peptide from the influenza virus polymerase 1, was sequentially converted to
      ASNENMETI, which binds to Db with an affinity similar to that of ASNENMETM.
      Although all positions examined influenced peptide binding, peptide residue no. 2
      (P2) was of particular importance. Therefore, each of the 20 naturally occurring
      amino acids were inserted at this position to investigate their effects on
      peptide-MHC interaction. The results indicated that amino acids having side
      chains with charged or ring structures were deleterious, while non-polar and
      polar residues were either neutral or facilitated binding to different degrees.
      Our data also indicated that every residue of the peptide contributes to the
      stability of the MHC-peptide complex, and the final affinity is dependent on the
      nature of the amino acids at each position, not just on those at a small number
      of anchor positions. The results also suggested that increased stability, as
      indicated by the half-life of the peptide-MHC class I complex, might play an
      important role in selecting the immunodominant epitope.

PMID- 7643855
TI  - Component C3 of hagfish complement has a unique structure: identification of
      native C3 and its degradation products.
AB  - A protein from hagfish serum that cross-reacted with the third component of
      hagfish complement (C3) was purified to homogeneity and its structural properties
      were compared with those of C3 which has a two-subunit chain structure (115 and
      72 kDa). This protein (designated C3b), when purified from plasma, consisted of
      three disulfide-linked polypeptide chains (77, 72 and 30 kDa). On
      immunoelectrophoresis, purified C3b migrated more rapidly towards the anode than
      the beta mobility of C3. However, immunochemical analysis revealed that C3b,
      after the first step in its purification, consisted of two disulfide-linked
      polypeptide chains (105 and 72 kDa). Treatment of C3b with methylamine, prior to
      spectrophotometric titration of the free sulfhydryl groups, did not significantly
      affect the end-point of the titration, suggesting the absence of a thioester bond
      in this molecule. Analysis of the amino acid sequences of the amino-termini of
      the subunits of C3b revealed that 77 amino acid residues at the amino-terminus of
      the native alpha chain were missing from both the 77-kDa and the 105-kDa
      polypeptides from C3b. These results indicate that the C3b in this study was
      analogous to mammalian C3b. Furthermore, amino acid sequencing data indicated
      that most of the native C3 from hagfish serum has an irregular two-subunit
      (alpha+gamma and beta)-linked structure, as a result of one-sided processing of
      putative hagfish pro-C3 at the beta-alpha processing site exclusively. Moreover,
      it appears that only the molecular features of degenerated hagfish C3 (C3b) are
      altered during its purification to generate a three-chain structure.

PMID- 7643856
TI  - Invariant chain (CD74) gene regulation: enhanced expression associated with
      activation of protein kinase C delta in a murine B lymphoma cell line.
AB  - The invariant chain (Ii, CD74) is a transmembrane glycoprotein that is
      transiently associated with the MHC class II antigens in the endoplasmic
      reticulum and in endocytic vesicles. An activator of protein kinase C (PKC), 12-O
      tetradecanoyl-1,2-phorbol 13-acetate (TPA), was found to enhance expression of Ii
      mRNA in the murine B lymphoma cell line, A20, 6-48 hr following treatment. In
      contrast, TPA did not induce the Ii in NIH 3T3 fibroblasts. TPA addition to
      either cell line activated PKC. Pretreatment of A20 cells with the PKC
      inhibitors, staurosporine or chelerythrine chloride, for 5 or 20 min prior to
      addition of TPA, decreased Ii mRNA levels when compared to cells treated with TPA
      alone. A 20 min preincubation with the highly specific PKC inhibitor, calphostin
      C, completely blocked the TPA enhanced expression of the Ii suggesting that
      activation of PKC was responsible for TPA increased Ii mRNA levels. IFN-gamma
      also blocked the TPA increased Ii mRNA levels. Constitutive expression of Ii mRNA
      was decreased by treatment with staurosporine but not chelerythrine chloride or
      calphostin C, suggesting that non-PKC protein kinases may also be important for
      maintaining high levels of Ii mRNA in these cells. Western blot analysis using
      PKC isotype specific antibodies showed that A20 cells express PKC delta
      abundantly whereas NIH 3T3 cells express primarily PKC alpha. These data suggest
      that a PKC delta mediated signal transduction pathway plays a crucial role in up
      regulation of the Ii.

PMID- 7643857
TI  - Alternative splicing of CD79a (Ig-alpha/mb-1) and CD79b (Ig-beta/B29) RNA
      transcripts in human B cells.
AB  - The CD79a (Ig-alpha/mb-1) and CD79b (Ig-beta/B29) molecules form a membrane
      heterodimer that is non-covalently associated with surface membrane
      immunoglobulin and is the major signaling component of the B cell antigen
      receptor complex. We have defined variant RNA transcripts for both CD79a (Ig
      alpha/mb-1) and CD79b (Ig-beta/B29) which appear to arise by alternative
      splicing. These splice variants are predicted to encode truncated forms of these
      molecules that result in the deletion of the entire extracellular Ig-like domain
      of CD79b and of a major portion of the extracellular domain of CD79a. The
      presence of these short transcripts in a variety of human B cells and B cell
      lines was established by an RNAse protection assay. The definition of these
      variant transcripts provides a basis for a continuing effort to define variant
      protein products of CD79a and CD79b and examine their role in B cell physiology.

PMID- 7643858
TI  - An alternative view of T-cell receptor-MHC interaction: T-cell receptor binds
      transversally to the alpha-helices of the MHC molecule.
AB  - We have attempted to elucidate the relative orientation of the T-cell receptor
      (TCR) to the major histocompatibility complex (MHC)-antigen complex during
      antigen recognition, using the T-cell response to B10.A (I-Ek) and B10.A(5R) (I
      Eb) mice to the 1-23(H) peptide derived from glycoprotein D of the herpes simplex
      virus. The 1-23(H)-specific T-cells derived from both B10.A and B10.A(5R) mice
      use the same set of V alpha genes and a different array of V beta genes. The
      CDR1s of these TCR beta chains share residues at particular positions. The CDR2s
      of the TCR beta chains have a negative charge, which correlates with I-Eb
      reactivity and with the positively charged polymorphic residues residing at the C
      terminal end of the alpha-helix of the I-Eb beta chain of the class II molecule.
      Taken together, the data suggest that the TCR beta chain interacts with both the
      alpha and beta chains of the MHC class II molecule, as does the TCR alpha chain.

PMID- 7643859
TI  - Characterization of a gene coding for a type IIo bacterial IgG-binding protein.
AB  - Two antigenic classes of non-immune IgG-binding proteins can be expressed by
      group A streptococci. One antigenic group of proteins is recognized by an
      antibody prepared against the product of a cloned fcrA gene (anti-FcRA). In this
      study, the immunogen used to prepare the antibody that defines the second
      antigenic class was shown to be the product of the emm-like (emmL) gene of M
      serotype 55 group A isolate, A928. The emmL55 gene expressed in E. coli produced
      an M(r) approximately 58,000 molecule which bound human IgG1, IgG2, IgG3 and
      IgG4, as well as horse, rabbit and pig IgG in a non-immune fashion. These
      properties are characteristic of the previously described type IIo IgG-binding
      protein isolated from this strain. In addition, the recombinant protein was
      reactive with human serum albumin and fibrinogen. The emmL 55 gene sequence was
      analysed and found to have the organization and sequence characteristics of a
      typical class I emm-like gene.

PMID- 7643861
TI  - Generators of the early and late median thenar premotor potentials.
AB  - The generator sources of the median thenar premotor potentials (PMPs) have
      remained elusive despite debate in the literature. By studying the median nerve
      in the hand with a variety of bipolar and referential recording montages, we
      systematically examined the possible near-field and far-field sources that may
      determine these potentials. The results suggest that the early PMP is a near
      field potential recorded by G1 and generated by the median nerve traversing the
      distal carpal tunnel. The late PMP represents a far-field potential generated by
      the median digital nerve fibers as they pass from the palm volume into the thumb
      volume. Characteristics of the late PMP are explained using the leading/trailing
      dipole (L/TD) model of far-field potential generation. The diagnostic utility of
      these PMPs is questionable, since they are recorded from "regions" along the
      nerve rather than from more clearly defined sites.

PMID- 7643860
TI  - A murine antibody to Shigella dysenteriae type 1 employs V-genes that contain a
      rearranged codon for the lambda light chain.
AB  - The cDNA coding for a hybridoma anti Shigella dysenteriae type 1 antibody (3707
      E9) has been cloned, and sequenced. Binding patterns with fragments of the
      bacterial polysaccharide antigen had already been studied in detail. The VH
      sequence utilizes the VH441 gene, first identified amongst beta-(1,6)galactan
      binding antibodies, while the VL is closely related to the V lambda 1 gene. We
      found that the VL3707 E9 gene employed a VL-J combinatorial joining leading to a
      rare Trp-->Leu substitution at position L96.

PMID- 7643862
TI  - Lysosomal enzyme activities in skeletal muscle of patients with neuromuscular
      diseases.
AB  - Activities of nine lysosomal enzymes and pH-dependent isozyme patterns of alpha
      mannosidase were examined in the skeletal muscle of patients with neuromuscular
      diseases, and the ratios of these enzyme activities in leukocytes to those in
      myocytes (L/M ratio) were determined. The activities of enzymes with a high L/M
      ratio were markedly increased in the muscles of patients with Duchenne muscular
      dystrophy (DMD), myotonic dystrophy (MyD), or polymyositis (PM). In contrast,
      those which showed a low L/M ratio were increased in the muscles of amyotrophic
      lateral sclerosis (ALS) and disuse muscle atrophy (DUA). The isozyme pattern of
      alpha-mannosidase in DMD muscle resembled that in leukocytes, while those in ALS
      and DUA muscle resembled that in normal muscle. These results may suggest that
      the increased activity of lysosomal enzymes in the muscles of patients with DMD,
      MyD, or PM is due primarily to infiltrating leukocytes, while that in patients
      with ALS or DUA is due to intramyofiber lysosomes.

PMID- 7643863
TI  - Amyloidosis causing a progressive myopathy.
AB  - A 62-year-old woman developed profound weakness secondary to a progressive
      myopathy associated with primary systemic amyloidosis. The characteristic apple
      green birefringent amyloid deposits were demonstrated surrounding individual
      muscle fibers in Congo red stained sections. Electron microscopy demonstrated
      amyloid filaments in close apposition to muscle fibers exhibiting excessive
      corrugations of the sarcolemmal membrane. The pathological features of
      progressive amyloid myopathy associated with primary systemic amyloidosis are
      distinct from the intracellular amyloid deposits characteristic of sporadic
      inclusion body myositis and inherited inclusion body myopathy.

PMID- 7643864
TI  - Influence of aging and the motor unit type on the inverse relationship between
      the refractory period and the conduction velocity of the alpha motor nerve
      fibers.

PMID- 7643865
TI  - Bilateral ulnar handcuff neuropathies with segmental conduction block.

PMID- 7643866
TI  - The abnormalities of the blink reflex in spinal cord infarction.

PMID- 7643867
TI  - Deficiency of laminin alpha 2-chain mRNA in muscle in a patient with merosin
      negative congenital muscular dystrophy.

PMID- 7643868
TI  - Reservations on the motor unit number estimates based on the automated analysis
      of F-responses.

PMID- 7643869
TI  - F tacheodispersion estimated from single? Motor units in the F responses (a
      reply)

PMID- 7643870
TI  - Nerve conduction biopsy correlation in over 100 consecutive patients with
      suspected neuropathy.

PMID- 7643871
TI  - Motor neuron disease: a primary disorder of corticomotoneurons?

PMID- 7643872
TI  - AAEM case report #29: Prolonged paralysis after neuromuscular blockade.
AB  - Nondepolarizing neuromuscular blocking agents (NMBA) are being used with
      increasing frequency in critically ill patients. Recently, many centers have
      described patients with prolonged muscle weakness after long-term use of these
      agents, either alone or in combination with other agents or disorders. Brief
      weakness lasting several hours to several days is probably the result of
      prolonged neuromuscular blockade, while more prolonged weakness lasting several
      weeks to months is, in all likelihood, caused by a myopathy. Patients with this
      myopathic disorder have flaccid paralysis with intact cognition and sensation.
      Electrodiagnostic findings include decreased M-wave amplitudes, positive waves
      and fibrillations, and rapid recruitment of small amplitude short duration,
      polyphasic motor unit potentials. Muscle biopsy findings include atrophy of type
      I and type II fibers, myofiber necrosis, and selective loss of thick
      myofilaments. The myopathy is believed to be related to the prolonged use of NMBA
      either alone or in combination with other disorders or medications, particularly
      corticosteroids. The weakness experienced by these patients leads to additional
      respiratory compromise, difficulty weaning from the ventilator, and prolonged
      hospitalization.

PMID- 7643873
TI  - Single fiber electromyography of extraocular muscles: a sensitive method for the
      diagnosis of ocular myasthenia gravis.
AB  - We performed single fiber electromyography (SFEMG) in the superior rectus and
      levator palpebralis (SR-LP) muscles of 17 patients with pure ocular myasthenia
      gravis (MG) and 9 controls. Thirteen patients were also assessed with SFEMG in
      the orbicularis oculi (OO) muscle. All the MG patients but none of the control
      subjects showed abnormal SFEMG jitter in the SR-LP muscles. On the other hand,
      only 62% of the MG patients had abnormal SFEMG jitter in the OO muscle. The
      procedure was well tolerated by the patients, and complications were minor. We
      conclude that SFEMG of the SR-LP muscles is a safe and highly sensitive technique
      for the diagnosis of ocular MG.

PMID- 7643874
TI  - Lateral rectus EMG and contractile responses elicited by cat abducens
      motoneurons.
AB  - Stimulation of 41 single, abducens nucleus motoneurons in the cat evoked
      electromyographic (EMG) and contractile responses in the ipsilateral lateral
      rectus muscle. Separate, bipolar, fine wire EMG recording electrodes in the
      global and orbital muscle layers showed that 22 muscle units were confined to the
      global layer, 8 to the orbital layer, and 11 units were contained in both
      ("bilayer") muscle layers. "Bilayer" units demonstrated significantly greater
      twitch (P < or = 0.002) and maximum tetanic (P < or = 0.001) tensions as well as
      faster fusion frequencies (P < or = 0.022) than either global or orbital units.
      "Bilayer" units also showed the lowest average kt values (the slope of the linear
      relationship between motoneuron stimulation frequency and isometric tetanic
      tension). "Bilayer" units were predominantly fast fatigable (FF). Global units
      displayed all muscle unit types including all the nontwitch (NT) units. Orbital
      units were identified as slow fatigable (SF) and fast fatigue resistant (FR).

PMID- 7643875
TI  - A quantitative study of the pancuronium antagonism at the motor endplate in human
      organophosphorus intoxication.
AB  - Nine patients with organophosphorus (OP) intoxication developing neuromuscular
      transmission defects were given pancuronium 1, 2, or 4 mg intravenously (IV).
      Thirteen patient controls with hypoxic encephalopathy received similar dosages.
      The responses were monitored electrophysiologically using single and repetitive
      nerve stimulation (20 and 50 Hz). In OP patients, pancuronium did not alter the
      amplitude of the single CMAP, whereas its repetitive discharges were reduced.
      Severe neuromuscular blocks were reversed only partially by pancuronium 4 mg. In
      less severe blocks, 1 and 2 mg resulted in marked improvement. In the patient
      controls, pancuronium 4 mg induced a severe neuromuscular block but not with 1
      and 2 mg. Pancuronium dosages necessary to reverse severe OP-induced
      neuromuscular blockade produce a neuromuscular block when AChE activity is
      normal. Low dosages have little effect on normal neuromuscular transmission, but
      improve the block to a mild degree and may be useful as part of treatment in OP
      intoxications.

PMID- 7643876
TI  - A fractal characterization of the type II fiber distribution in the extensor
      digitorum longus and soleus muscles of the adult rat.
AB  - A method is proposed for the quantitative characterization of fiber type spatial
      distribution by means of the (correlation) fractal dimension. The method is
      applied to type II fiber distributions of the soleus and extensor digitorum
      longus muscles of the adult rat. The results obtained suggest that these
      distributions have fractal properties with a strong tendency for spreading, more
      pronounced in soleus muscle. The density of muscle fibers or the age do not seem
      to alter the features of the distribution. Computer-generated random patterns
      have virtually the same fractal dimension as the extensor digitorum longus
      distributions but fail to approximate those of the soleus muscle. This fractal
      method could find application as an alternative in the quantitative assessment of
      the fiber type grouping.

PMID- 7643877
TI  - Number and relative size of thenar motor units estimated by an adapted multiple
      point stimulation method.
AB  - An adapted multiple point stimulation (AMPS) method is described for estimating
      the number and relative size of thenar motor units. With this method, the median
      nerve was stimulated at various sites from the wrist to the elbow. To avoid
      alternation, only two or three clearly identifiable surface-recorded motor unit
      action potentials (S-MUAPs) were recruited at each point by incremental
      stimulation. A total of 10 S-MUAPs, elicited from four to five distinct
      stimulation points, was used to calculate the average S-MUAP size. By dividing
      the maximum M-potential size by that value, a motor unit number estimate (MUNE)
      was derived. In 59 healthy volunteers, from 19 to 87 years old, the mean average
      S-MUAP size was 87 +/- 27.6 microV.ms and the mean MUNE was 278 +/- 113 motor
      units. When performed repeatedly, the results were reproducible. The number of
      motor units declined exponentially with age while average S-MUAP sizes increased
      only moderately. To assess the validity of the AMPS method, its results were
      correlated with those obtained using the F-response technique. The correlation
      coefficient was 0.83 (P < 0.001).

PMID- 7643878
TI  - Quantification of normal dystrophin mRNA following myoblast transplantation in
      mdx mice.
AB  - A mutagenesis RT-PCR method was used to detect normal dystrophin mRNA following
      the injection of normal myoblasts in mdx mice using two immunosuppressors. A
      specific sequence of the dystrophin mRNA (257 bp) was amplified by RT-PCR from
      the muscle total RNA. MaeIII digestion of the amplified products allowed us to
      distinguish the normal messenger of dystrophin from the dystrophic one and to
      establish the percentage of normal and of dystrophic (mdx) dystrophin mRNA.
      Normal dystrophin mRNA was detected using this technique in mdx muscles
      transplanted with histocompatible normal myoblasts. For this type of
      transplantation, no significant difference in the percentage of normal dystrophin
      mRNA was observed between immunosuppressed mice and those not immunosuppressed.
      No normal dystrophin mRNA was, however, observed in mdx mice following
      histoincompatible normal myoblast transplantation without immunosuppression. When
      such transplantations were done in mice immunosuppressed with cyclosporine or FK
      506, normal dystrophin mRNA accounted for 31% and 36% of the total dystrophin
      mRNA, respectively. In fact, one animal immunosuppressed with FK-506 expressed as
      much as 57% of normal dystrophin mRNA. These results thus show that FK-506 makes
      it possible to restore dystrophin expression to a level comparable to that
      observed in DMD carriers that are usually asymptomatic.

PMID- 7643879
TI  - Thoracic spinal nerve and root conduction: a magnetic stimulation study.
AB  - We describe a technique of magnetic coil (MC) stimulation of the thoracic spinal
      nerves and roots in 12 normal subjects and a patient with diabetes mellitus. We
      kept the MC flat against the vertebral column in the midline over T-7, T-8, and T
      9 spinous processes and obtained compound muscle action potentials from the upper
      rectus abdominis, external oblique, and intercostal muscles. We obtained mean
      latencies to these muscles after stimulation in the posterior axillary line. We
      noted that the onset latencies remained fixed despite increasing the intensity of
      stimulation from 30% to 100% and on moving the coil up to 3 cm lateral to the
      spinous processes suggesting that the stimulation of the fastest conducting
      fibers was occurring at a fixed site, most likely at the intervertebral foramina.
      Prolonged latencies in the diabetic patient confirmed the diagnosis of
      radiculoneuropathy.

PMID- 7643880
TI  - A clinical trial of active management of labor.
AB  - BACKGROUND: Active management of labor is a multifaceted program that, as
      implemented at the National Maternity Hospital in Dublin, is associated with a
      lower rate of cesarean delivery than the rate usually found in the United States.
      We conducted a randomized trial to evaluate the efficacy of this approach in
      lowering the rate of cesarean section among women delivering their first babies.
      METHODS: We randomly assigned 1934 nulliparous women at low risk of complications
      of pregnancy, before 30 weeks' gestation, to active management of labor or to a
      usual-care group. The components of active management were customized childbirth
      classes; strict criteria for the diagnosis of labor; standardized management of
      labor, including early amniotomy and treatment with high-dose oxytocin; and one
      to-one nursing. A low-risk subgroup was defined as including women with full
      term, uncomplicated pregnancies who spontaneously went into labor (the protocol
      eligible subgroup). Women meeting these criteria who had been randomly assigned
      to the active-management group were admitted to a separate unit where their labor
      was managed by trained, certified nurse-midwives. RESULTS: There was no
      difference between groups in the rate of cesarean section either among all women
      (active management, 19.5 percent; usual care, 19.4 percent) or in the protocol
      eligible subgroup (active management, 10.9 percent; usual care, 11.5 percent). In
      the protocol-eligible subgroup, the median duration of labor was shortened by 2.7
      hours by active management (from 8.9 to 6.2 hours), and the rate of maternal
      fever was lower (7 percent vs. 11 percent, P = 0.007). The percentage of women in
      whom labor lasted longer than 12 hours was three times higher in the usual-care
      group than in the active-management group (26 percent vs. 9 percent, P < 0.001).
      CONCLUSIONS: Active management of labor did not reduce the rate of cesarean
      section in nulliparous women but was associated with a somewhat shorter duration
      of labor and less maternal fever.

PMID- 7643881
TI  - Race, sex, drug use, and progression of human immunodeficiency virus disease.
AB  - BACKGROUND: The rates of progression of human immunodeficiency virus (HIV)
      infection and survival have been reported to differ among sociodemographic
      groups. It is unclear whether these differences reflect biologic differences or
      differences in access to medical care. METHODS: We measured disease progression
      and survival in a cohort of 1372 patients seropositive for HIV who were treated
      at a single urban center (median follow-up, 1.6 years). We calculated the rates
      of survival for the entire cohort and the rates of progression to the acquired
      immunodeficiency syndrome (AIDS) or death among the 740 patients who presented
      without AIDS. We used Cox proportional-hazards analysis to examine factors
      associated with progression to AIDS and death. RESULTS: Progression to AIDS or
      death was associated with a CD4 cell count of 201 to 350 per cubic millimeter
      (relative risk, 2.0; P < 0.001), the presence of symptoms at base line (relative
      risk, 2.0; P < 0.001), prior antiretroviral therapy (relative risk, 1.7; P =
      0.003), and older age (relative risk per year of age, 1.02; P = 0.03). However,
      there was no relation between disease progression and sex, race, injection-drug
      use, income, level of education, or insurance status. In the entire cohort, a
      lower CD4 cell count, a diagnosis of AIDS, older age, and the receipt of
      antiretroviral therapy before enrollment were associated with an increased risk
      of death, whereas the use of prophylaxis against pneumocystis pneumonia,
      zidovudine use after enrollment, and having a job at base line were associated
      with lower risks of death. There was no significant difference in survival
      between men and women, blacks and whites, injection-drug users and those who did
      not use drugs, or patients whose median annual incomes were $5,000 or less and
      those whose incomes were more than $5,000. CONCLUSIONS: Among patients with HIV
      infection who received medical care from a single urban center, there were no
      differences in disease progression or survival associated with sex, race,
      injection-drug use, or socioeconomic status. Differences found in other studies
      may reflect differences in the use of medical care.

PMID- 7643882
TI  - A comparison of hirudin with heparin in the prevention of restenosis after
      coronary angioplasty. Helvetica Investigators.
AB  - BACKGROUND: The likelihood of restenosis is a major limitation of coronary
      angioplasty. We studied whether hirudin, a highly selective inhibitor of thrombin
      with irreversible effects, would prevent restenosis after angioplasty. We
      compared two regimens of recombinant hirudin with heparin. METHODS: We randomly
      assigned 1141 patients with unstable angina who were scheduled for angioplasty to
      receive one of three treatments: (1) a bolus dose of 10,000 IU of heparin
      followed by an intravenous infusion of heparin for 24 hours and subcutaneous
      placebo twice daily for three days (382 patients), (2) a bolus dose of 40 mg of
      hirudin followed by an intravenous infusion of hirudin for 24 hours and
      subcutaneous placebo twice daily for three days (381 patients), or (3) the same
      hirudin regimen except that 40 mg of hirudin was given subcutaneously instead of
      placebo twice daily for three days (378 patients). The primary end point was
      event-free survival at seven months. Other end points were early cardiac events
      (within 96 hours), bleeding and other complications of the study treatment, and
      angiographic measurements of coronary diameter at six months of follow-up.
      RESULTS: At seven months, event-free survival was 67.3 percent in the group
      receiving heparin, 63.5 percent in the group receiving intravenous hirudin, and
      68.0 percent in the group receiving both intravenous and subcutaneous hirudin (P
      = 0.61). However, the administration of hirudin was associated with a significant
      reduction in early cardiac events, which occurred in 11.0, 7.9, and 5.6 percent
      of patients in the respective groups (combined relative risk with hirudin, 0.61;
      95 percent confidence interval, 0.41 to 0.90; P = 0.023). The mean minimal
      luminal diameters in the respective groups on follow-up angiography at six months
      were 1.54, 1.47, and 1.56 mm (P = 0.08). CONCLUSIONS: Although significantly
      fewer early cardiac events occurred with hirudin than with heparin, hirudin had
      no apparent benefit with longer-term follow-up.

PMID- 7643883
TI  - Treatment with bivalirudin (Hirulog) as compared with heparin during coronary
      angioplasty for unstable or postinfarction angina. Hirulog Angioplasty Study
      Investigators.
AB  - BACKGROUND: Heparin is often administered during and after coronary angioplasty
      to prevent closure of the dilated vessel. However, ischemic or hemorrhagic
      complications occur in 5 to 10 percent of treated patients. We studied whether
      these complications could be prevented when the direct thrombin inhibitor
      bivalirudin (Hirulog) was used in place of heparin. METHODS: We performed a
      double-blind, randomized trial in 4098 patients undergoing angioplasty for
      unstable or postinfarction angina. Patients were assigned to receive either
      heparin or bivalirudin immediately before angioplasty. The primary end point were
      death in the hospital, myocardial infarction, abrupt vessel closure, or rapid
      clinical deterioration of cardiac origin. RESULTS: In the total study group,
      bivalirudin did not significantly reduce the incidence of the primary end point
      (11.4 percent, vs. 12.2 percent for heparin) but did result in a lower incidence
      of bleeding (3.8 percent vs. 9.8 percent, P < 0.001). In the prospectively
      stratified subgroup of 704 patients with postinfarction angina, bivalirudin
      therapy resulted in a lower incidence of the primary end point (9.1 percent vs.
      14.2 percent, P = 0.04) and a lower incidence of bleeding (3.0 percent vs. 11.1
      percent, P < 0.001), but in a similar cumulative rate of death, myocardial
      infarction, and repeated revascularization in the six months after angioplasty
      (20.5 percent vs. 25.1 percent, P = 0.17). CONCLUSIONS: Bivalirudin was at least
      as effective as high-dose heparin in preventing ischemic complications in
      patients who underwent angioplasty for unstable angina, and it carried a lower
      risk of bleeding. Bivalirudin, as compared with heparin, reduced the risk of
      immediate ischemic complications in patients with postinfarction angina, but this
      difference was no longer apparent after six months.

PMID- 7643884
TI  - Virologic characteristics of subclinical and symptomatic genital herpes
      infections.
AB  - BACKGROUND: The frequency, pattern, and anatomical sites of subclinical shedding
      of herpes simplex virus (HSV) in the genital tract, along with factors that
      predict such shedding, have not been well characterized. METHODS: We studied
      prospectively the clinical and virologic course of genital herpes in 110 women.
      The women kept symptom diaries and provided daily samples from the vulva, cervix,
      and rectum for viral culture. RESULTS: During a median follow-up of 105 days,
      subclinical shedding of virus was identified in 36 of 65 women (55 percent) with
      HSV type 2 (HSV-2), in 16 of 31 women (52 percent) with HSV type 1 (HSV-1) and
      HSV-2, and in 4 of 14 women (29 percent) with only HSV-1. Among women with
      genital HSV-2 infection, subclinical shedding occurred on a mean of 2 percent of
      the days. The mean duration of viral shedding during subclinical episodes was 1.5
      days, as compared with 1.8 days during symptomatic episodes. HSV was isolated
      from several sites in the genital tract and rectum in 17 percent of subclinical
      episodes and 22 percent of symptomatic episodes. Half the episodes of subclinical
      shedding of HSV occurred within seven days of a symptomatic recurrence. The risk
      of subclinical shedding increased with the frequency of symptomatic recurrences.
      Subclinical shedding was more frequent among women with more than 12 recurrences
      per year than among those with no symptomatic recurrences (odds ratio, 3.3; 95
      percent confidence interval, 1.4 to 7.9); it was also more frequent among women
      who had recently acquired genital herpes (odds ratio for women with HSV acquired
      in the past year as compared with those who had had the infection for a year or
      more, 1.85; 95 percent confidence interval, 1.1 to 3.1). CONCLUSIONS: Among women
      with a history of genital herpes infection, subclinical shedding of HSV is common
      and accounts for nearly one third of the total days of reactivation of HSV
      infection in the genital tract. Women with frequent symptomatic recurrences also
      have frequent subclinical shedding and may be at high risk for transmitting HSV.

PMID- 7643885
TI  - Images in clinical medicine. Castleman's disease.

PMID- 7643887
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 29-1995. A 65-year-old man with mediastinal Hodgkin's disease and
      a pelvic mass.

PMID- 7643886
TI  - Disability income, cocaine use, and repeated hospitalization among schizophrenic
      cocaine abusers--a government-sponsored revolving door?
AB  - BACKGROUND: Many patients with serious mental illness are addicted to drugs and
      alcohol. This comorbidity creates additional problems for the patients and for
      the clinicians, health care systems, and social-service agencies that provide
      services to this population. One problem is that disability income, which many
      people with serious mental illness receive to pay for basic needs, may facilitate
      drug abuse. In this study, we assessed the temporal patterns of cocaine use,
      psychiatric symptoms, and psychiatric hospitalization in a sample of
      schizophrenic patients receiving disability income. METHODS: We evaluated 105
      male patients with schizophrenia and cocaine dependence at the time of their
      admission to the hospital. They had severe mental illness and a long-term
      dependence on cocaine, with repeated admissions to psychiatric hospitals; many
      were homeless. The severity of psychiatric symptoms and urinary concentrations of
      the cocaine metabolite benzoylecgonine were evaluated weekly for 15 weeks.
      RESULTS: Cocaine use, psychiatric symptoms, and hospital admissions all peaked
      during the first week of the month, shortly after the arrival of the disability
      payment, on the first day. The average patient spent nearly half his total income
      on illegal drugs. CONCLUSIONS: Among cocaine-abusing schizophrenic persons, the
      cyclic pattern of drug use strongly suggests that it is influenced by the monthly
      receipt of disability payments. The consequences of this cycle include the
      depletion of funds needed for housing and food, exacerbation of psychiatric
      symptoms, more frequent psychiatric hospitalization, and a high rate of
      homelessness. The troubling irony is that income intended to compensate for the
      disabling effects of severe mental illness may have the opposite effect.

PMID- 7643888
TI  - A partisan assault on science--the threat to the CDC.

PMID- 7643889
TI  - When disability benefits make patients sicker.

PMID- 7643890
TI  - Herpes-like DNA sequences, AIDS-related tumors, and Castleman's disease.

PMID- 7643891
TI  - Herpes-like DNA sequences, AIDS-related tumors, and Castleman's disease.

PMID- 7643892
TI  - Periorbital edema in Kaposi's sarcoma.

PMID- 7643893
TI  - Rapid genotyping of hepatitis C virus.

PMID- 7643894
TI  - Adverse reproductive outcomes and young maternal age.

PMID- 7643895
TI  - Adverse reproductive outcomes and young maternal age.

PMID- 7643896
TI  - Prevention and treatment of the complications of diabetes mellitus.

PMID- 7643897
TI  - Prevention and treatment of the complications of diabetes mellitus.

PMID- 7643898
TI  - Hydroxyurea in essential thrombocytosis.

PMID- 7643899
TI  - Hydroxyurea in essential thrombocytosis.

PMID- 7643900
TI  - Hydroxyurea in essential thrombocytosis.

PMID- 7643901
TI  - Arsenic and mercury in traditional Chinese herbal balls.

PMID- 7643902
TI  - Do-not-resuscitate orders at a teaching hospital in Japan.

PMID- 7643903
TI  - Shattuck Lecture--biomedical research enters the steady state.

PMID- 7643905
TI  - [Neurobiology of language processing].
AB  - Neurobiological mechanisms underlying language functions can be modeled in the
      framework of Hebb's cell assembly theory. According to this approach, meaningful
      words, but not meaningless pseudowords, have a cortical representation in
      strongly coupled ensembles of neurons distributed over wide cortical areas. Cell
      assemblies with different cortical topographies can be assumed for different word
      types. These hypotheses give rise to empirical predictions that can be tested in
      behavioral and electrophysiological experiments with healthy and neurologically
      impaired subjects. Results of a series of experiments providing support for the
      above assumptions are summarized.

PMID- 7643906
TI  - The static vestibuloocular reflex in lower vertebrates after a transient gravity
      deprivation during an early period of life.

PMID- 7643904
TI  - [Proteasomes. Complex proteases lead to a new understanding of cellular
      regulation through proteolysis].
AB  - Proteasomes are large multicatalytic protease complexes which fulfill central
      functions in major proteolytic pathways of the eukaryotic cell. Two types of
      proteasomes are known: the cylindrically shaped 20S proteasome (700 kDa) and the
      26S proteasome (1700 kDa) which contains the 20S proteasome as a functional core.
      Proteasomes are needed for stress-dependent and ubiquitin-mediated proteolysis.
      They are involved in degradation of abnormal, short-lived, and regulatory
      proteins. Proteasomes are important for cell differentiation and adaptation to
      environmental changes. Proteasomes have been shown to function in the control of
      the cell cycle and are suggested to be involved in antigen presentation by
      processing of intracellular proteins to antigenic peptides.

PMID- 7643907
TI  - [Stress proteins: their growing significance in medicine].
AB  - In response to a variety of "emergencies", cells produce several stress proteins
      (heat shock proteins, HSP) that provide them with higher resistance and are able
      to repair protein damage. Their expression is regulated by heat shock
      transcription factors. Stress proteins are arousing growing interest in medicine,
      as major antigens in some infections and certain autoimmune diseases and also
      because of their possible involvement in the development and therapy of cancer.
      Elevated levels of stress proteins protect tissues and organs against ischemic
      injury and reduce infarct size. Stress proteins may also serve as a marker in
      diagnostic studies and in toxicology.

PMID- 7643908
TI  - Molecular phylogeny of Metazoa (animals): monophyletic origin.
AB  - The phylogenetic relationships within the kingdom Animalia (Metazoa) have long
      been questioned. Focusing on the lowest eukaryotic multicellular organisms, the
      metazoan phylum Porifera (sponges), it remained unsolved if they evolved
      multicellularity independently from a separate protist lineage (polyphyly of
      animals) of derived from the same protist group as the other animal phyla
      (monophyly). After having analyzed genes typical for multicellularity (adhesion
      molecules/receptors and a nuclear receptor), we present evidence that Porifera
      should be placed in the kingdom Animalia. We therefore suggest a monophyletic
      origin for all animals.

PMID- 7643909
TI  - The antinociception induced by beta-endorphin administered intrathecally is
      mediated by the activation of mu- and kappa-opioid receptors in the rat.
AB  - The antinociception induced by beta-endorphin given supraspinally has been
      previously demonstrated to be mediated by the stimulation of epsilon-, but not mu
      , delta- or kappa-opioid receptors in rats and mice. The present study was
      designed to determine what types of opioid receptors in the spinal cord are
      involved in the antinociception induced by intrathecally (i.t.) administered beta
      endorphin. Antinociception was assessed by the tail-flick test in male Sprague
      Dawley rats. CTOP (0.9-6.6 nmol), a selective mu-opioid receptor antagonist, or
      nor-BNI(13.6-95.3 nmol), a selective kappa-opioid receptor antagonist, given i.t.
      dose-dependently reversed i.t. administered beta-endorphin-induced inhibition of
      the tail-flick response. On the other hand, naltrindole (6.6-44.4 nmol), a
      selective delta-opioid receptor antagonist, or beta-endorphin (1-27) (1-6.7
      nmol), a selective epsilon-opioid receptor antagonist given i.t., did not
      antagonize the inhibition of the tail-flick response induced by i.t. administered
      beta-endorphin. The results are consistent with the previous study in mice [Tseng
      LF and Collins KA (1992) Eur J Pharmacol 214: 59-65] that the antinociception
      induced by beta-endorphin given i.t. is mediated by the stimulation of mu- and
      kappa-, but not delta- and epsilon-opioid receptors.

PMID- 7643910
TI  - The effects of desipramine on thyroid hormone concentrations in rat brain.
AB  - The effects of the antidepressant desipramine on the tissue concentrations of
      thyroxine and triiodothyronine in 9 different regions of the brain and also in
      the pituitary and liver were investigated in male rats. The investigations were
      carried out at three different times of the light/dark cycle: 5 a.m., 1 p.m. and
      11 p.m. After fourteen days' treatment with 20 mg/kg/day desipramine by gavage
      the concentrations of triiodothyronine in the frontal and parieto-occipital
      cortex were significantly higher than in the saline-treated controls, those in
      the hippocampus lower and those in the 6 remaining brain regions the same. In 8
      areas of the brain the concentrations of thyroxine were lower in the desipramine
      treated rats and the tissue ratios of triiodothyronine to thyroxine were enhanced
      in 6 regions. These effects are most likely the result of the action of
      desipramine on the activity of the isoenzyme 5'II deiodinase. This enzyme
      catalyzes the deiodination of thyroxine to triiodothyronine in rat brain and its
      activity has recently been reported to be enhanced by desipramine. The observed
      effects were dose-dependent and also strongly dependent upon the time within the
      24 h light/dark cycle at which the hormone concentrations were measured. No
      effects of desipramine were seen in the pituitary or liver after 14 days'
      treatment, or in various areas of the central nervous system 24 h after
      administration. In view of the psychotropic properties of thyroid hormones, it
      seems possible that the observed increases in triiodothyronine concentrations,
      particularly in cortical areas, are involved in the mechanisms of action of
      desipramine.

PMID- 7643911
TI  - Facilitation of noradrenaline release from rat brain slices by beta
      adrenoceptors.
AB  - The present study examined whether stimulation of beta-adrenoceptors facilitated
      noradrenaline release in the rat brain. Electrical stimulation-evoked overflow of
      tritium from rat cerebral cortical, hypothalamic and hippocampal slices labelled
      with 3H-noradrenaline was measured during superfusion for 100 min. Tissue slices
      were electrically simulated (1 Hz, 20 mA, 2 ms, 2 min), at 20 (S1) and 70 (S2)
      min after the onset of superfusion. The nonselective beta-adrenoceptor agonist
      isoproterenol (0.1-10 nM) enhanced stimulation-evoked overflow of tritium from
      slices of cerebral cortex, hypothalamus and hippocampus in a concentration
      dependent manner; mean S2/S1 ratios with 10 nM isoproterenol were 161 +/- 11%,
      142 +/- 15% and 143 +/- 12% of control, respectively, in the three brain regions.
      The facilitatory effect of isoproterenol in cerebral cortical slices was
      antagonized by propranolol (50 nM), a nonselective beta-adrenoceptor antagonist,
      and by the beta 1- and beta 2-selective adrenoceptor antagonists ICI 89,406 (1
      nM) and ICI 118,551 (1 nM), respectively. The beta 1- and beta 2-selective
      adrenoceptor agonists prenalterol and albuterol (0.1-10 nM), respectively, also
      increased stimulation-evoked overflow of tritium from cerebral cortical slices;
      these effects were antagonized by beta-adrenoceptor antagonists. These findings
      suggest that stimulation of beta-adrenoceptors enhance noradrenaline release from
      rat cerebral cortical, hypothalamic and hippocampal slices; this release
      mechanism appears to involve both beta 1- and beta 2-adrenoceptor subtypes. These
      facilitating presynaptic receptors may be involved in mediating the
      antidepressant-like behavioral effects of beta 2-adrenoceptor agonists.

PMID- 7643912
TI  - A kinetic investigation of the pulmonary metabolism of dopamine in rats shows
      marked differences compared with noradrenaline.
AB  - The aim of this study was to investigate the deamination of dopamine in the
      intact pulmonary circulation of isolated lungs of the rat. The first part of the
      study showed that dopamine is not converted to noradrenaline by dopamine-beta
      hydroxylase (DBH) when dopamine is perfused through isolated lung preparations
      with monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT) inhibited.
      Hence, it was not necessary to inhibit DBH in subsequent experiments. The
      metabolite profile for deamination of dopamine in the lungs was examined by
      determining whether MAO and semicarbazide-sensitive amine oxidases (SSAO)
      contribute to the deamination of dopamine (and noradrenaline), and by determining
      the activity of MAO (kMAO) for the metabolism of dopamine. Lungs were perfused
      with 1 nmol/l 3H-dopamine or 3H-noradrenaline with COMT inhibited and, in
      experiments to determine the contribution of SSAO to deamination, with MAO
      inhibited. Inhibition of MAO reduced the deamination of dopamine and
      noradrenaline by 99.8% and 98.6%, respectively, indicating that MAO, and not
      SSAO, was responsible for deamination of the catecholamines in the lungs. The
      kMAO value for deamination of dopamine was 3.89 min-1. Further experiments were
      carried out to determine the contributions of MAO-A and MAO-B to the deamination
      of dopamine in lungs perfused with 1 nmol/l 3H-dopamine and 100 nmol/l lazabemide
      or 300 nmol/l Ro41-1049, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7643913
TI  - A comparison of the effects of TMB-8 and nifedipine on pressor responses to alpha
      1- and alpha 2-adrenoceptor agonists in pithed rats.
AB  - TMB-8 has been characterized as an inhibitor of the release of Ca2+ from
      intracellular pools. We have studied the modification of the pressor responses to
      selective alpha 1-adrenoceptor agonists (methoxamine and phenylephrine), and to
      selective alpha 2-adrenoceptor agonists (B-HT 920 and B-HT 933) in pithed rats,
      produced by TMB-8. We have compared this modification with that produced by the
      calcium antagonist nifedipine. Nifedipine (100 micrograms/kg, 300 micrograms/kg,
      and 1000 micrograms/kg) inhibited in a dose-dependent manner the pressor
      responses to the alpha 1- and alpha 2-adrenoceptor agonists, the dose-response
      curves to the alpha 2-adrenoceptor agonists being shifted further to the right.
      TMB-8 at a dose of 3000 micrograms/kg did not modify the pressor effects of the
      alpha 1-adrenoceptor agonists, and neither did it reinforce the inhibition of
      such responses produced by nifedipine. By contrast, TMB-8 pretreatment (0.03
      micrograms/kg, 0.3 micrograms/kg, 3 micrograms/kg, 30 micrograms/kg, 300
      micrograms/kg and 3000 micrograms/kg) inhibited the responses to both alpha 2
      adrenoceptor agonists, the inhibition being more pronounced with B-HT 920. A
      similar effect was obtained with 0.03 micrograms/kg TMB-8 and 0.3 microgram/kg
      TMB-8, particularly in the case of B-HT 920. It was stronger with higher doses,
      but similar for all doses over 3 micrograms/kg. The inhibition of the pressor
      responses mediated by the stimulation of alpha 2-adrenoceptors by TMB-8 was less
      in rats treated with the Ca2+ entry promoter BAY K 8644 (300 micrograms/kg), and
      could also be reduced by the continuous infusion of CaCl2 (0.25
      microgram/min).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7643914
TI  - Inhibitory presynaptic imidazoline receptors on sympathetic nerves in the rabbit
      aorta differ from I1- and I2-imidazoline binding sites.
AB  - The involvement of imidazoline receptors in modulation of noradrenaline release
      was investigated in the rabbit aorta preincubated with [3H]noradrenaline and
      superfused with physiological salt solution containing cocaine, corticosterone
      and propranolol. After blockade of alpha 2-autoreceptors by rauwolscine, the
      electrically evoked tritium overflow was inhibited by various imidazolines and
      guanidines. The rank order of potency was BDF 7579 (4-chloro-2-isoindolinyl)
      guanidine) > or = BDF 6143 (4-chloro-2-(2-imidazolin-2-ylamino)-isoindoline) >
      BDF 6100 [2-(2-imidazolin-2-ylamino)-isoindoline] > clonidine > ST587 (2-(2
      chloro-5-trifluoromethylphenylimino) imidazolidine nitrate) > or = cirazoline >
      tolazoline > idazoxan > phentolamine. Comparison of the potencies of these drugs
      with those previously found for the presynaptic imidazoline receptors in the
      rabbit pulmonary artery revealed a very good correlation. In contrast, no
      positive correlation was found with their affinities for the I1- and I2
      imidazoline binding sites in bovine adrenal medullary membranes and with their
      lipophilicity (log P values). The electrically evoked tritium overflow was also
      inhibited by the recently identified endogenous imidazoline receptor ligand
      agmatine, but was not affected by amiloride. In further series of experiments,
      the ability of putative antagonist at presynaptic imidazoline receptors to
      counteract the inhibitory effect of imidazoline derivatives was determined.
      Amiloride, imidazole-4-acetic acid and 1-benzylimidazole did not attenuate the
      inhibitory effect of BDF 6143 on the electrically evoked tritium overflow. In
      contrast, rauwolscine antagonized the inhibitory effect of various imidazolines;
      rauwolscine was clearly less potent in antagonizing the effect of clonidine, BDF
      6143 and cirazoline (apparent pA2 6.48-7.32) than in antagonizing that of
      oxymetazoline and moxonidine (apparent pA2 8.33 and 8.12, respectively). In a
      final series of experiments, BDF 6143 (under the conditions applied a selective
      agonist at presynaptic imidazoline receptors) proved to be considerably less
      potent in inhibiting tritium overflow evoked by high K+ than by electrical
      stimulation, whereas moxonidine (in rabbit aorta a selective agonist at
      presynaptic alpha 2-adrenoceptors) exhibited similar potency in inhibiting the
      overflow evoked by both methods of stimulation.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7643915
TI  - Age-related decrease in the effect of parathyroid hormone-related protein on
      cytosolic free calcium level and tension in rat aortic smooth muscle.
AB  - Age-related changes in the effect of parathyroid hormone-related protein (PTHrP)
      on the cytosolic free calcium level ([Ca2+]i) and on the tension in rat aortic
      smooth muscle were investigated. The possible involvement of cAMP, a second
      messenger of PTHrP, in such changes was also investigated. Spiral aortic strip
      preparations without endothelium from 8-weeks, 6-months, and 24-months old rats
      were treated with fura 2/AM, and the fluorescence ratio R340/380, an index of
      [Ca2+]i was measured. Simultaneously, the tension of the preparations was
      measured. PTHrP-(1-34) and dibutyryl cAMP produced concentration-dependent
      decreases in the tension and in R340/380 in aortas precontracted with
      phenylephrine (10(-7) M). These effects were significantly lower in the aortas of
      24-months old rats than in the vessels of 8-weeks and 6-months old rats. The
      effects were similar in the aortas of 8-weeks and 6-months old rats. PTHrP-(1-34)
      concentration-dependently increased cAMP production in vascular smooth muscle
      cells (VSMCs) from 8-weeks old rats. However, the increase in cAMP production was
      significantly lower in cultured VSMCs from 6-months and 24-months old rats than
      in cells from 8-weeks old rats. These results suggest that the reduced cAMP
      production stimulated by PTHrP and the reduced effects of cAMP with aging might
      contribute to the age-related changes in the decreases in tension and [Ca2+]i in
      response to PTHrP in the rat aorta.

PMID- 7643916
TI  - Suramin analogs, divalent cations and ATP gamma S as inhibitors of ecto-ATPase.
AB  - Ecto-nucleotidases are plasma membrane-bound enzymes that sequentially
      dephosphorylate extracellular nucleotides such as ATP. This breakdown of ATP and
      other nucleotides obscures the characterization and classification of P2
      (nucleotide) receptors. We therefore studied suramin and several of its analogs,
      divalent cations and ATP gamma S for their ability to inhibit ecto-ATPase in
      human blood cells. Suramin itself and Ni2+ were the more potent, non-competitive
      inhibitors with micromolar affinity. ATP gamma S also displayed micromolar
      affinity and inhibited ecto-ATPase competitively. The data obtained with the
      divalent cations demonstrate that coordination of the phosphate chain but not the
      N7 of the adenine ring is required for the breakdown of ATP by ecto-ATPase.
      Divalent cations that coordinate both the phosphate chain and N7 inhibit ecto
      ATPase in a non-competitive manner.

PMID- 7643917
TI  - Effects of CIS-19, a novel PAF receptor antagonist, on PAF-induced eosinophil
      recruitment and enhancement of superoxide anion generation in guinea-pigs.
AB  - We examined the effects of a novel platelet-activating factor (PAF) receptor
      antagonist, CIS-19 [cis-2-(3,4-dimethoxyphenyl)-6-isopropoxy-7-methoxyl-1-(N
      methylforma mido)- 1,2,3,4-tetrahydronaphthalene], on PAF-induced inflammatory
      cells recruitment into airways and enhancement of superoxide anion (O2-)
      generation from cells retrieved by bronchoalveolar lavage (BAL) in urethane
      anesthetized guinea-pigs. Administration of PAF (30 ng/kg, i.v.) produced a
      selective increase of eosinophils into airways, but no significant increase of
      the number of macrophages, neutrophils or lymphocytes. CIS-19 (2.5 and 5 mg/kg,
      i.v.) significantly inhibited the eosinophil recruitment induced by PAF. In
      vitro, PAF, phorbol 12-myristate 13-acetate (PMA) and N-formyl-methionyl-leucyl
      phenylalanine (FMLP) directly stimulated generation of O2- from BAL cells in a
      concentration-dependent manner. CIS-19 (10(-7)-10(-4) M) inhibited production of
      O2- induced by PAF (10(-7) M) in a concentration-dependent manner with an EC50
      value of 0.84 microM, but not induced by PMA (0.5 microgram/ml) or FMLP (10(-7)
      M). Administration of PAF (5 ng/kg, i.v.) enhanced markedly PMA (0.5
      microgram/ml) and FMLP (10(-7) M)-induced generation of O2- by 80.2% and 51.3%,
      respectively. The enhancing effect of PAF was maximal in cells harvested 5 min
      after the addition of PAF and then declined to baseline level at 60 min. These
      responses were inhibited by administration of CIS-19 (0.5-2.5 mg/kg, i.v.) or BN
      52021 (5 mg/kg, i.v.). The results indicate that CIS-19 is potent in inhibition
      of PAF-induced airway inflammatory response and may have therapeutic potential as
      an anti-inflammatory drugs.

PMID- 7643918
TI  - The myostimulating effect of tissue kallikrein on rat uterus.
AB  - The mechanism of the myostimulating activity of rat tissue kallikrein on rat
      uterus was re-examined using uterus from kininogen-deficient rats and HOE 140 (D
      Arg[Hyp3, Thi5, D-Tic7, Oic8]bradykinin), a specific bradykinin receptor-B2
      antagonist. The uterus from kininogen-deficient rats was 50 times less sensitive
      to rat kallikrein than that from normal rats. HOE 140 (6 to 60 nM) inhibited the
      contracting effects of bradykinin and of rat kallikrein. Porcine kallikrein had
      no effect on rat uterus. Bradykinin and rat kallikrein induced a relaxation of
      rat duodenum. The duodenum from kininogen-deficient rats was 100 times less
      sensitive to rat kallikrein than the duodenum from normal rats. HOE 140 (0.6 to 3
      nM) inhibited the relaxing effects of bradykinin and of kallikrein. Preincubation
      of rat kallikrein with aprotinin (Trasylol) abolished the effects of kallikrein
      on smooth muscles. HOE 140 inhibited the amidolytic activity of tissue kallikrein
      with a Ki value of 220 microM. HOE 140, at micromolar concentrations, suppressed
      the kininogenase activity of tissue kallikrein. Plasma of deficient rats
      contained 0.7% of the normal levels of kininogens. After washing the blood
      vessels with saline, kininogens were present in uterine homogenates but not in
      duodenal homogenates from both rat strains.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7643919
TI  - Functional consequences of inhibition of nucleotide breakdown in rat vas
      deferens: a study with Evans blue.
AB  - The effect of Evans blue on nucleotide breakdown, nucleotide-evoked contractions
      and electrically evoked contractions, overflow of ATP and overflow of tritium
      (after labelling with [3H]-noradrenaline) was studied in rat vas deferens. Pieces
      of vas deferens degraded 83 to 85% of added ATP, ADP and 2-methyl-thio ATP (all
      100 microM) over 30 min. Evans blue (100 microM) reduced this degradation to 22
      to 26%. Nucleotides elicited contraction with potency declining in the order
      alpha,beta-methylene ATP > 2-methylthio ATP > ATP > ADP. Evans blue (100 microM)
      shifted the concentration-response curve of alpha, beta-methylene ATP to the
      right and increased the maximum. Concentration-response curves of ATP, ADP and 2
      methylthio ATP, in contrast, were shifted to the left and responses were much
      potentiated. In the presence of Evans blue, the rank order of potency was ATP > 2
      methylthio ATP > alpha, beta-methylene ATP > ADP. Electrical field stimulation
      (100 pulses at 10 Hz) elicited contraction and an overflow of tritium and ATP.
      Evans blue (100 microM) did not alter the contraction and the evoked overflow of
      tritium but increased 24-fold the evoked overflow of ATP. The results indicate
      that Evans blue may serve as an-albeit impure-ecto-nucleotidase inhibitor in
      functional experiments. Such experiments demonstrate that the low potency of ATP
      (and also ADP and 2-methylthio ATP) in eliciting contraction, and the small size
      of the overflow of ATP upon sympathetic nerve stimulation, are due to rapid
      breakdown.

PMID- 7643920
TI  - Characterization of non-adrenergic [3H]clonidine binding sites in rat stomach:
      high affinity of imidazolines, guanidines and sigma ligands.
AB  - We have identified and characterized non-adrenergic [3H]clonidine binding sites
      in rat stomach. The binding of [3H]clonidine was rapid, reversible, partly
      specific (as defined by cirazoline 0.1 nmol/l), saturable and of high affinity.
      The specific binding of [3H]clonidine to rat stomach membranes was concentration
      dependently inhibited by various imidazolines and guanidines including the sigma
      site ligand 1,2-di-(2-tolyl)guanidine (DTG), by the butyrophenone derivative (+)
      3-PPP[(R)-3-(3-hydroxyphenyl)-N-propylpiperidine]; the latter two compounds are
      also known to exhibit affinity for sigma sites. In contrast, rauwolscine,
      histamine, ranitidine and the non-hydrolysable GTP-analogue Gpp(NH)p (5'
      guanylylimidodiphosphate) did not, or with negligible affinity, inhibit
      [3H]clonidine binding. In most cases, the competition curves were best fitted to
      a two-site model. The rank order of affinity for the high affinity site (in a few
      cases for a single detectable site) was as follows: cirazoline > idazoxan > or =
      DTG > (+)-3-PPP > chlonidine > guanabenz > haloperidol. This rank order is not
      compatible with the pharmacological properties of either I1- or I2-imidazoline
      binding sites. However, the ability of haloperidol, (+)-3-PPP and DTG to displace
      [3H]clonidine (the latter two with high affinity) suggests that the [3H]
      clonidine binding sites in rat stomach may be related to sigma-like sites.

PMID- 7643922
TI  - Sleeping on the job.

PMID- 7643921
TI  - Ligand binding profile of the rat metabotropic glutamate receptor mGluR3
      expressed in a transfected cell line.
AB  - A cDNA clone encoding the rat metabotropic glutamate receptor mGluR3 was stably
      transfected into human embryonic kidney 293 cells. Receptor-expressing cell lines
      were characterized by centrifugation binding assays using [3H]glutamate as
      radioligand. The rank order of affinity was L-glutamate > (1S,3R)-1
      aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) > L(+)-2-amino-3
      phosphonopropionic acid (L-AP3) > quisqualic acid > L(+)-2-amino-4
      phosphonobutyric acid (L-AP4) > ibotenic acid. The active enantiomers of several
      phenylglycines displayed Ki values of 300 to 400 microM. The nonactive
      enantiomers and the standard ionotropic glutamate receptor ligands N-methyl-D
      aspartic acid (NMDA), (R,S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
      acid (AMPA) and kainic acid only weakly displaced [3H]glutamate. In this cell
      line, L-glutamate and (2S,3S,4S)-alpha-(Carboxycyclopropyl)-glycine (L-CCG-I)
      reduced cAMP levels in a dose-dependent manner. The sensitivity of this system
      and its easy applicability make it feasible to envisage ligand binding assays on
      cell lines expressing cloned receptors as useful screening tools to discover and
      characterize new and specific agonists and antagonists.

PMID- 7643924
TI  - Recent infant mortality trends in North Carolina.

PMID- 7643923
TI  - Transfer patient, transmit information.

PMID- 7643925
TI  - Racial differences in North Carolina infant mortality.

PMID- 7643926
TI  - Tularemia in North Carolina, 1965-1990.

PMID- 7643927
TI  - Rocky Mountain Spotted Fever, tick paralysis, Lyme disease, and Ehrlichiosis.

PMID- 7643928
TI  - Between a rock and a Charybdisian place. Baclofen (Lioresal) overdose.

PMID- 7643929
TI  - A drive in the autumn mist.

PMID- 7643931
TI  - Tattoo removal using the Alexandrite laser.

PMID- 7643930
TI  - Substance abuse consultation in a teaching hospital.

PMID- 7643933
TI  - To be or not to be a "nurse": it's time for five nursing levels.

PMID- 7643932
TI  - Ophthalmoscopic findings of diabetic retinopathy.

PMID- 7643934
TI  - Health education and chronic illness--putting the family into family centered
      care.

PMID- 7643935
TI  - What is this "thing" called, ethics? Reflections on a personal journey.

PMID- 7643937
TI  - English professor's surgery prompts a letter.

PMID- 7643936
TI  - Transcultural and political education in Jordan and Washington D.C.

PMID- 7643938
TI  - NE physicians organize to collectively negotiate managed care contracts.

PMID- 7643939
TI  - Present and future aspects of cystic fibrosis.

PMID- 7643940
TI  - Cystic fibrosis: the past 25 years.

PMID- 7643941
TI  - Diagnosis of cystic fibrosis.
AB  - Applying the sweat-test as the first choice of test when a diagnosis of cystic
      fibrosis is suspected is still common practice and advisable. Since the cloning
      of the CFTR gene more than 400 different cystic fibrosis (CF) mutations have
      already been identified. The use of CF mutation analysis for diagnostic purposes
      in CF has therefore remained elusive so far. It is advised to perform sweat-tests
      as previously described by Gibson and Cooke. In this study we have re-evaluated
      the results of sweat-tests of 1905 subjects performed in our hospital over a
      period of 9 years (1983-1992). In 1825 subjects where the CF diagnosis was not
      made, the mean sodium value obtained was 15.5 +/- 9.2 mmol/l. The upper limit of
      the normal range (2 SD above the mean) is 34 mmol/l. Re-examination of all 239
      sweat sodium values (80.9 +/- 19.5 mmol/l) in 80 newly diagnosed CF patients
      (all: Na+ > 70 mmol/l) revealed that 5% of the values were below 50 mmol/l, the
      lowest sweat value obtained being 27 mmol/l. Based on these results, we recommend
      in case of clinical suspicion of CF and sweat values above 30 mmol/l to repeat
      the sweat-test and to determine both sodium and chloride for optimal
      discrimination.

PMID- 7643942
TI  - Present and future treatment modalities for gastrointestinal diseases in cystic
      fibrosis.
AB  - In recent years knowledge of the basic defect of CF has increased enormously.
      Many new drugs and treatment strategies are being introduced in the clinic.
      Nevertheless, there are a number of unsolved problems in the treatment of
      malabsorption and malnutrition. In spite of innovative technical and
      pharmacological improvement of pancreatic enzyme preparations maldigestion is
      still a problem. Better enzymes and coatings are needed. The integrated action of
      enzymatic digestion, intestinal motility and absorption is not under control. The
      role of malnutrition in the development of complications and in the outcome of
      the disease is still under discussion. The importance of a high energy intake is
      now generally accepted, but the question is how to achieve this. Tube feeding,
      endoscopic gastrostomy and the use of diets with a high energy content are
      becoming more popular. In CF the relationship between gastro-oesophageal reflux
      and lung complications is not well understood, but GER is frequently recognized.
      In the absence of CF GER is also associated with a number of pulmonary and upper
      airway diseases. The incidence of liver fibrosis and cholestatic liver disease is
      increasing with age. The problem is how to identify the patients at risk. The use
      of choleretic drugs has shown promising results in preliminary studies. Gene
      therapy in pancreatic and gastrointestinal pathology will be restricted to the
      liver. The biliary tract could be an interesting target, if patients at risk can
      be identified. In conclusion, new drugs and new strategies are necessary for the
      future implementation of the results of new insights in CF.

PMID- 7643943
TI  - Isolation and treatment of cystic fibrosis patients with lung infections caused
      by Pseudomonas (Burkholderia) cepacia and multiresistant Pseudomonas aeruginosa.
AB  - Cross-infection with Pseudomonas aeruginosa and Pseudomonas cepacia has been
      shown sometimes to occur between cystic fibrosis (CF) patients in some CF
      centres, in some summer camps and during some social contacts between CF
      patients. Cohort isolation and improved hygienic precautions, however, have
      successfully been employed in some CF centres resulting in a decrease or
      elimination of cross-infection. Chronic P. aeruginosa infection is in most CF
      patients preceded by a period of intermittent colonization. Early aggressive
      chemotherapy (oral ciprofloxacin and nebulized colistin for 3 weeks) every time
      P. aeruginosa is detected in sputum has significantly decreased the incidence of
      new chronic infection in CF patients. Chronic P. aeruginosa infection can be
      treated by "maintenance chemotherapy" (= chronic suppressive chemotherapy). The
      principle is to restore lung function repeatedly by regular 2-week courses of
      intensive intravenous treatment every 3 months in the CF centre and adding daily
      inhalations of colistin between the courses, and sometimes also by giving oral
      ciprofloxacin during these intervals to unstable patients. Eradication of P.
      cepacia infection is virtually never obtained by antibiotic treatment with, e.g.,
      ceftazidime and tobramycin or co-trimoxazole. Chronic suppression with doxycyclin
      or co-trimoxazole may give rise to some improvement in the clinical symptoms.

PMID- 7643944
TI  - Maintenance treatment with antibiotics in cystic fibrosis patients. Sense or
      nonsense?
AB  - The majority of patients with cystic fibrosis (CF) have chronic lung infection
      with a variety of organisms. It is accepted clinical practice to treat acute
      exacerbations of infection with appropriate oral or intravenous antibiotics. The
      aim of this paper is to review the use of maintenance antibiotics for these
      patients with chronic pulmonary infection. There is clinical trial evidence to
      support the use of maintenance treatment for patients chronically infected with
      Staphylococcus aureus or Pseudomonas aeruginosa. No such evidence is available in
      the case of Haemophilus influenzae or Burkholderia cepacia. Chronic infection
      with Staphylococcus aureus is commonly treated with maintenance oral
      flucloxacillin and chronic infection with Pseudomonas aeruginosa either with 3
      monthly intravenous antibiotics or long-term aerosol antibiotics. Further
      clinical trials need to be performed on many aspects of maintenance treatment for
      CF patients with chronic pulmonary infection.

PMID- 7643945
TI  - Effect of rhDNase on lung function and quality of life in adult cystic fibrosis
      patients.
AB  - Accumulation of viscous sputum enhances lung damage in patients with cystic
      fibrosis. High contents of DNA, released by leucocytes, are the major cause of
      the high viscosity of this sputum. Recombinant human DNase I (rhDNase) decreases
      viscoelastic properties of sputum in cystic fibrosis and improves lung function.
      We have investigated the effect of rhDNase over a period of 6 weeks, 2.5 mg once
      daily, on lung function and quality of life in 12 adult patients with cystic
      fibrosis. Significant improvements in FEV1, IVC and daily peak flow values were
      measured. Airway resistance and FVC did not improve significantly. The cause of
      the improvements found is probably due to recruitment of previously, due to mucus
      plugging, unventilated lung areas. In addition, the awareness of symptoms related
      to sputum retention improved, although subjective parameters on general well
      being and physical condition remained unchanged.

PMID- 7643946
TI  - Lung transplantation in patients with cystic fibrosis. The Groningen Lung
      Transplantation Group.
AB  - Worldwide more than 600 heart-lung or lung transplantations have been performed
      in patients with cystic fibrosis and end-stage respiratory disease. At the
      University Hospital in Groningen 10 patients with cystic fibrosis underwent
      bilateral sequential lung transplantation until April 1994. The 1-year survival
      was 76%, which is similar to that of lung transplant recipients with other
      diseases. Postoperative problems were mainly related to acute rejection, chronic
      graft dysfunction and infection. The main problem for further extension of the
      lung transplantation program is the persistent shortage of usable donor-organs
      for cystic fibrosis patients, especially of small-sized donors.

PMID- 7643948
TI  - The patient with cystic fibrosis in the next 25 years.

PMID- 7643947
TI  - Gene therapy for cystic fibrosis.

PMID- 7643949
TI  - Prevalence of Alzheimer's disease and other dementing disorders in Pamplona,
      Spain.
AB  - We investigated the prevalence of dementing disorders in the city of Pamplona,
      Spain, using a door-to-door two-phase approach. We first administered the
      Cambridge Examination of Mental Disorders of the Elderly (CAMDEX) to all
      survivors, as of March 1, 1991, of a probability sample of the total population
      identified in 1989 (n = 1,127). Using specified diagnostic criteria, the study
      neurologists extensively investigated those subjects who screened positive on
      CAMDEX. We found 194 subjects affected by dementia, 119 had Alzheimer's disease;
      51 vascular or mixed dementia, and 16 secondary dementia. The prevalence of both
      dementia and Alzheimer's disease increased steeply with advancing age and was
      consistently higher in women. The prevalence of combined vascular and mixed
      dementia increased less rapidly with age, and was generally higher in men.
      Alzheimer's disease was the most common type of dementia. Our prevalence figures
      for dementia and Alzheimer's disease are similar to those previously reported in
      Europe.

PMID- 7643950
TI  - Spatial distribution of stroke mortality in Spain, 1975-1986.
AB  - Cerebrovascular diseases (CVDs) constitute the most frequent cause of death in
      Spain. In order to identify the geographical pattern of CVD mortality, age- and
      sex-specific as well as age-adjusted mortality rates (ICD-8,9 rubrics 430-438)
      were calculated for the period 1975-1986 for each province in the country. Maps
      were constructed after categorization of mortality rates by quintile levels. In
      general, the geographical pattern was similar for the different age and sex
      strata. While most provinces in the northern half presented low or medium
      mortality, geographical areas located in the south, displayed rates in the
      uppermost quintiles. These results suggest that the spatial distribution of CVD
      mortality in Spain is not random and that the potential determinants underlying
      this geographical distribution, such as type of stroke, incidence, fatality,
      diagnostic or certification practices and competing causes of death, have an
      impact that is independent of age and sex and strongly associated with spatial
      location. Furthermore, these results can help in identifying high-risk
      populations.

PMID- 7643951
TI  - Epidemiology of Creutzfeldt-Jakob disease in the United States, 1979-1990:
      analysis of national mortality data.
AB  - The trends and current incidence of Creutzfeldt-Jakob disease (CJD) was examined
      by using a unique and potentially high sensitive source for case ascertainment.
      We analyzed death certificate information for 1979-1990 from US multiple-cause-of
      death mortality data, compiled by the National Center for Health Statistics,
      Centers for Disease Control and Prevention. We evaluated death certificate data
      for US residents for whom CJD was listed as one of the multiple causes of death
      on the death certificate (046.1) from the International Statistical
      Classification of Diseases, Injuries, and Causes of Death (9th revision). Age
      adjusted and age-specific CJD death rates by gender, race, and region were
      calculated to measure the disease incidence because of the rapidly fatal course
      of the disease for most patients with CJD. We identified 2,614 deaths with CJD
      listed on the death certificates. The average annual age-adjusted mortality rate
      was 0.9 deaths per million persons (range 0.8-1.1). The mean age at death was 67
      years. CJD-related deaths were uncommon among persons younger than 50 years of
      age (4.3% of all deaths). The highest average annual mortality rate was for those
      persons aged 70-74 years (5.9 deaths per million persons). A slight majority
      (53.0%) of the deaths was in females, but the age-adjusted mortality rate was 1.2
      times higher for males. Most deaths (94.8%) were in whites; the mortality rate
      for blacks was only 40% of that for whites. The age-adjusted CJD mortality rate
      in the United States is similar to published estimates of the crude incidence of
      CJD worldwide.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7643952
TI  - The British Neurological Surveillance Unit: a nation-wide scheme for the
      ascertainment of rare neurological disorders.
AB  - The British Neurological Surveillance Unit was set up in January 1993 with the
      aim of co-ordinating and improving the ascertainment of rare neurological
      disorders in the United Kingdom by using a system of nation-wide active
      surveillance. The unit provides a service for individual investigators who must
      first submit possible studies to a scientific advisory committee. Once accepted
      the condition is listed on a report card which is sent to every member of the
      British neurological community every month. The cards are easy to use, and all
      the reporting neurologist has to do is tick a box indicating whether a case has
      (or has not been) seen. At the end of every month the individual investigators
      then initiate further follow-up by contacting the reporting neurologists. In the
      first year of operation the scheme has assisted in the surveillance of 6
      disorders and the following number of verified cases have so far been
      ascertained: polio in adults (n = 0); acute psychological disorders in patients
      with epilepsy (n = 75); Guillain-Barre syndrome in the south of England (n = 32);
      epilepsia partialis continua (n = 40); amyloid neuropathy (n = 12), and agenesis
      of the corpus callosum (n = 24). The monthly response rates are between 65 and
      75%, with the eventual aim of achieving over 90% after the scheme has become more
      established.

PMID- 7643953
TI  - A study of birth order and multiple sclerosis in multiplex families.
AB  - Birth order position for affected siblings was examined for 88 sibships having 2
      or more cases of multiple sclerosis (MS). The data show that MS patients are
      randomly ordered by birth within these multiplex sibships. The data therefore do
      not support the hypothesis that MS occurs in siblings because of a common
      environmental exposure as defined by proximity in birth order position.

PMID- 7643954
TI  - Prevalence of neurological disorders in Haute-Vienne department (Limousin region
      France).
AB  - The Limousin region had at present one of the largest elderly populations in
      France and in Europe. To determine the frequency of certain neurological
      disorders in the elderly, a neuroepidemiological survey was conducted in 1986
      1987 on a representative sample of the population in Haute-Vienne (the most
      population-dense department in the Limousin region). This study used a WHO
      protocol which was first introduced at the beginning of the 1980s. It had been
      previously tested in France on a pilot population in 1984. The prevalences of the
      principal neurological disorders encountered per 100,000 inhabitants were as
      follows: nonmigraine headache 5,059, migraine 4,270, epilepsy 788, completed
      stroke 1,445, transient ischemic attacks 657, neuropathy 1,642, Parkinson's
      disease 328, and dementia 197.

PMID- 7643955
TI  - Hospital morbidity due to head injuries in New Zealand in 1980-1988.
AB  - We studied the morbidity in New Zealand using hospital discharge data from 1980
      to 1988, and found a reduced head injury (HI) rate over this time overall, but no
      change in the rate among Maori males and an increased rate among Maori females.
      In 1988 the rate was 228/100,000 with peaks among males and females aged under
      10, males aged 15-25, and both sexes over 84 years old. The rate among young
      Maori males was higher than in other groups until the age of 55. Motor vehicle
      crashes caused most head injuries, followed by falls, non-intentional incidents
      (such as sporting injuries), assaults and pedal cycle accidents. Maori females
      had a high rate of assault. Hospital stay was longest among pedestrians, and
      increased with increasing age due to co-morbidity. Prevention strategies were
      based on the causes of HI.

PMID- 7643956
TI  - Special issue honoring Dr. Robert Balazs.

PMID- 7643957
TI  - Development of the human hypothalamus.
AB  - The hypothalamus has been claimed to be involved in a great number of
      physiological functions in development, such as sexual differentiation (gender,
      sexual orientation) and birth, as well as in various developmental disorders
      including mental retardation, sudden infant death syndrome (SIDS), Kallman's
      syndrome and Prader-Willi syndrome. In this review a number of hypothalamic
      nuclei have therefore been discussed with respect to their development in health
      and disease. The suprachiasmatic nucleus (SCN) is the clock of the brain and
      shows circadian and seasonal fluctuations in vasopressin-expressing cell numbers.
      The SCN also seems to be involved in reproduction, adding interest to the sex
      differences in shape of the vasopressin-containing SCN subnucleus and in its VIP
      cell number. In addition, differences in relation to sexual orientation can be
      seen in this perspective. The vasopressin and VIP neurons of the SCN develop
      mainly postnatally, but as premature children may have circadian temperature
      rhythms, a different SCN cell type is probably more mature at birth. The sexually
      dimorphic nucleus (SDN, intermediate nucleus, INAH-1) is twice as large in young
      male adults as in young females. At the moment of birth only 20% of the SDN cell
      number is present. From birth until two to four years of age cell numbers
      increase equally rapidly in both sexes. After this age cell numbers start to
      decrease in girls, creating the sex difference. The size of the SDN does not show
      any relationship to sexual orientation in men. The large neurosecretory cells of
      the supraoptic (SON) and paraventricular nucleus (PVN) project to the
      neurohypophysis, where they release vasopressin and oxytocin into the blood
      circulation. In the fetus these hormones play an active role in the birth
      process. Fetal oxytocin may initiate or accelerate the course of labor. Fetal
      vasopressin plays a role in the adaptation to stress--caused by the birth process
      -by redistribution of the fetal blood flow. Corticotropin-releasing hormone (CRH)
      neurons of the PVN play a central role in stress response. Thus fetal CRH neurons
      may play a role in the timing of the moment of birth. Recently, alterations have
      been described in peptidergic, aminergic and cholinergic transmitters in the
      hypothalamus in SIDS. Future research will have to establish whether these
      changes are part of the course of SIDS. A large proportion of the SON and PVN
      neurons also produce tyrosine hydroxylase (TH). In neonates the majority of TH
      immunoreactive neurons colocalizes vasopressin, while in the adult the majority
      of TH-positive neurons colocalizes oxytocin.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7643958
TI  - Mast cells in neuroimmune function: neurotoxicological and neuropharmacological
      perspectives.
AB  - Mast cells are located in close proximity to neurons in the peripheral and
      central nervous systems, suggesting a functional role in normal and aberrant
      neurodegenerative states. They also possess many of the features of neurons, in
      terms of monoaminergic systems, responsiveness to neurotrophins and neuropeptides
      and the ability to synthesise and release bioactive neurotrophic factors. Mast
      cells are able to secrete an array of potent mediators which may orchestrate
      neuroinflammation and affect the integrity of the blood-brain barrier. The 'cross
      talk' between mast cells, lymphocytes, neurons and glia constitutes a neuroimmune
      axis which is implicated in a range of neurodegenerative diseases with an
      inflammatory and/or autoimmune component, such as multiple sclerosis and
      Alzheimer's disease. Mast cells appear to make an important contribution to
      developing, mature and degenerating nervous systems and this should now be
      recognised when assessing the neurotoxic potential of xenobiotics.

PMID- 7643961
TI  - Effects of protein kinase C modulation on NMDA receptor mediated regulation of
      neurotransmitter enzyme and c-fos protein in cultured neurons.
AB  - The role of protein kinase C (PKC) in N-methyl-D-aspartate (NMDA) receptor
      mediated biochemical differentiation and c-fos protein expression was
      investigated in cultured cerebellar granule neurons. The biochemical
      differentiation of glutamatergic granule cells was studied in terms of the
      specific activity of phosphate-activated glutaminase, an enzyme treatment in the
      synthesis of the putative neurotransmitter pool of glutamate. When the partially
      depolarized cells were treated with NMDA for the last 1 to 3 days (between 2 and
      5 days in vitro), it elevated the specific activity of glutaminase. In contrast,
      NMDA had little effect on the activity of aspartate aminotransferase or of
      lactate dehydrogenase. Treatment of 10-day old granule neurons with NMDA also
      resulted in a marked increase in the immunocytochemically measured expression of
      c-fos protein. The increases in both the activity of glutaminase and the steady
      state level of c-fos protein were specific to the activation of NMDA receptors,
      as they were completely blocked by D,L-2-amino-5-phosphonovaleric acid. The
      specific stimulation of NMDA receptors in PKC-depleted granule neurons or in the
      presence of reasonably specific PKC inhibitors also produced significant
      elevation in the activity of glutaminase and the expression of c-fos protein.
      These increases were similar in magnitude to those observed in the granule
      neurons of the respective control groups. Our findings demonstrate that PKC is
      not directly involved in the NMDA receptor-mediated signal transduction processes
      associated with biochemical differentiation and c-fos induction in cerebellar
      granule neurons.

PMID- 7643962
TI  - The remote astroglial response (RAR): a holistic approach for evaluating the
      effects of lesions of the central nervous system.
AB  - The right dorsal lateral geniculate nucleus was stereotaxically destroyed in
      adult albino rats. After 3 to 150 days of survival the visual cortices from both
      hemispheres were processed for semithin histology, electron microscopy, GFAP
      immunohistochemistry and immunoblotting. In visual cortices with histologically
      disclosed degeneration of the geniculo-cortical tract, a hypertrophy of
      astrocytes without change in their total numbers was seen from postoperative day
      3. From day 7, a rise in GFAP immunoreactivity was observed, reaching its peak
      between days 11-14, after which a decrease occurred. Observations were confirmed
      by computer-assisted image analysis of immunohistochemical preparations. Using
      the immunoblot technique, relative GFAP levels were found to change in a fashion
      similar to immunohistochemical findings. This showed that synaptic degeneration
      triggered an up-regulation of GFAP synthesis in the perisynaptic astrocyte
      processes as a second, cytoskeletal phase of the astrocyte reaction. The
      phenomenon is denoted as the remote astroglial response (RAR) and is thought to
      be a marker of synapse removal during plastic changes either related to function
      or induced by lesions. An extrapolation is made to the possible significance of
      whole-brain GFAP levels in assessing the effects of focal CNS lesions.

PMID- 7643959
TI  - Neural cell adhesion molecule (NCAM) as a quantitative marker in synaptic
      remodeling.
AB  - The neural cell adhesion molecule (NCAM) participates in adhesion and neuritic
      outgrowth during nervous system development. In the adult brain, NCAM is
      considered to be involved in neuronal sprouting and synaptic remodeling. The NCAM
      concentration of brain tissue has proved to be a useful marker of these
      processes, especially when viewed in comparison with the concentration of a
      marker of mature synapses, e.g. D3-protein (SNAP-25) or synaptophysin. The
      present review focusses on studies of adult brain in which NCAM concentration
      estimates and NCAM/D3 ratios have been used to evaluate the rate of synaptic
      remodeling in brain damage and degenerative diseases.

PMID- 7643963
TI  - Development and isoproterenol-induced regulation of adrenoceptor binding in
      cultured rat neocortical explants is seen only with the beta-1, not with the beta
      2 subtype.
AB  - The presence and time-course of beta-adrenoceptor density in cultured explants of
      neocortex obtained from 6-day-old rat pups were investigated using a [125I]ICYP
      binding assay. A delayed, but more pronounced, increase in the receptor
      expression was observed as compared to the situation previously described in
      vivo. These changes only occurred for the beta 1-subtype of the receptor, whereas
      the beta 2-subtype binding remained constant up to 3 weeks in vitro. The delay of
      beta 1-adrenoceptor expression may be due to the incomplete presence of the
      proper maturational input, and the late enhancement of receptor expression to
      upregulation related to the absence in vitro of noradrenergic input. Decreased
      beta-adrenoceptor levels could be induced by chronic treatment of the beta
      agonist isoproterenol (1 microM) introduced either for 3 or 13 days. Again,
      changes in density were found only for the beta 1-adrenoceptor binding sites.
      There is no reduction of receptor density following return to control conditions
      for 10 days after a 3-day treatment with isoproterenol, demonstrating the ability
      of this model to attain its final receptor density notwithstanding the
      developmental insult.

PMID- 7643960
TI  - Expression and regulation of kainate and AMPA receptors in uncommitted and
      committed neural progenitors.
AB  - Here we review experimental evidence of non-NMDA glutamate receptor expression in
      the embryonic central nervous system. AMPA- and kainate-preferring glutamate
      receptor subunit mRNA transcripts are detected in embryonic neurons, glia and
      neural progenitors. Functional assays demonstrate that in some cell
      subpopulations ionotropic glutamate receptors are expressed by progenitors before
      synapse formation and terminal differentiation, and may be present before lineage
      determination is specified. The activation of these receptors triggers induction
      of immediate early gene transcription in progenitor cells. The cloning and
      transcriptional analysis of upstream regulatory regions of glutamate receptor
      genes governing their temporal and tissue-specific expression are also discussed.

PMID- 7643964
TI  - Effects of the organophosphate insecticide, monocrotophos, on
      acetylcholinesterase activity in the nile tilapia fish (Oreochromis niloticus)
      brain.
AB  - The neurotoxic effects of monocrotophos on the brain of the nile tilapia fish
      (Oreochromis niloticus) were examined, using a static bioassay under laboratory
      conditions. By probit analysis the 96 h LC50 value of monocrotophos was 4.9 mg/l.
      After 96 h exposure to acute levels of monocrotophos, the brain
      acetylcholinesterase (AChE) activity decreased progressively as the concentration
      of monocrotophos increased. In addition, four weeks following transfer to
      toxicant-free water after exposure to 1 mg monocrotophos, nile tilapia fish brain
      regained 95% of control AChE activity. The results indicate that inhibition of
      AChE activity in fish exposed to monocrotophos may serve as an indicator of
      hazard due to application of this chemical in the natural environment.

PMID- 7643966
TI  - Synaptic excitation mediated by AMPA receptors in rat cerebellar slices is
      selectively enhanced by aniracetam and cyclothiazide.
AB  - AMPA receptors mediate fast, glutamatergic synaptic transmission in the central
      nervous system. The time-course of the associated postsynaptic current has been
      suggested to be determined principally by the kinetics of glutamate binding and
      receptor desensitization. Aniracetam and cyclothiazide are drugs capable of
      selectively preventing desensitization of the AMPA receptor. To investigate the
      relevance of desensitization to fast synaptic transmission in the cerebellum we
      have tested these compounds against AMPA-induced depolarizations and postsynaptic
      potentials using the grease-gap recording technique. Aniracetam (1 microM-5 mM)
      and cyclothiazide (1 microM-500 microM) both enhanced the depolarising action of
      AMPA (1 microM) on Purkinje cells in a concentration-dependent manner. At the
      highest concentrations tested, the increases over controls were approximately
      600% and 800% respectively. Aniracetam also increased, in a concentration
      dependent manner, the amplitude of the evoked synaptic potentials of both
      parallel fibre-Purkinje cell and mossy fibre-granule cell pathways, with the
      highest concentrations tested enhancing the potentials by approximately 60% and
      75% respectively. These data suggest that, at two different synapses in the
      cerebellum, AMPA receptor desensitization occurs physiologically and is likely to
      contribute to the shape of fast synaptic currents.

PMID- 7643965
TI  - Polysialylation as a regulator of neural plasticity in rodent learning and aging.
AB  - Although generally accepted to play an important role in development, the precise
      functional significance of NCAM remains to be elucidated. Correlative and
      interventive studies suggest a role for polysialylated NCAM in neurite
      elaboration. In the adult NCAM polysialylation continues to be expressed in
      regions of the central nervous system which retain neuroplastic potential. During
      memory formation modulation of polysialylation on the synapse-enriched isoform of
      NCAM occurs in the hippocampus. The polysialylated neurons of this structure have
      been located at the border of the granule cell layer and hilar region of the
      dentate and their number increases dramatically during memory consolidation. The
      converse is also true for a profound decline in the basal number of
      polysialylated neurons occurs with ageing when neural plasticity becomes
      attenuated. In conclusion, it is suggested that NCAM polysialylation regulates
      ultrastructural plasticity associated with synaptic elaboration.

PMID- 7643967
TI  - Growth conditions differentially affect the constitutive expression of primary
      response genes in cultured cerebellar granule cells.
AB  - Cultured cerebellar granule cells underwent apoptotic degeneration when grown in
      medium containing 10 instead of 25 mM K+. Knowing that apoptosis is associated
      with changes in the expression of primary response genes, we have measured c-fos,
      zif/268, and c-jun mRNA levels during maturation of cultured granule cells grown
      in 10 or 25 mM K+. The constitutive expression of c-fos and zif/268 was
      differentially regulated by extracellular K+ concentration at 5 days of
      maturation in vitro (DIV), when cells grown under suboptimal conditions (i.e. in
      10 mM K+) are committed to degenerate. At this stage, c-fos mRNA levels were
      detectable only in cultures grown in 25 mM K+, whereas zif/268 mRNA levels were
      dramatically elevated in cultures grown in 10 mM K+. This provides one of the few
      conditions in which c-fos and zif/268 are differentially regulated in nerve
      cells. Substantial changes in c-jun, or beta-actin mRNA levels were detectable
      only at 7 DIV, when the percentage of apoptotic cells had already reached a
      plateau in cultures grown in 10 mM K+. We speculate that changes in the
      expression of zif/268 are important in the gene program associated with the
      induction of apoptosis by trophic deprivation in cultured neurons.

PMID- 7643970
TI  - Haemodynamic evaluation of paraparetic transient ischaemic attacks in childhood
      moyamoya disease.
AB  - The haemodynamic mechanisms responsible for the appearance of paraparetic
      transient ischaemic attacks in ten patients with childhood moyamoya disease who
      subsequently underwent bifrontal omental transplantation were investigated.
      Cerebral perfusion (CP) was measured with 99mTc-hexamethylene-propyleneamine
      oxime single photon computed tomography prior to and after administration of
      acetazolamide. Cerebral perfusion was obtained by dividing radioisotope uptake
      per pixel in regions of interest by that in cerebellum. Haemodynamic reserve was
      defined as [CP after acetazolamide--CP before acetazolamide]/CP before
      acetazolamide x 100. Amounts of CP in the anterior portion of the frontal lobe
      and in the paracentral lobule were 0.70 +/- 0.04 and 0.74 +/- 0.03, respectively,
      before appearance of the transient ischaemic attacks. The latter was
      significantly higher than the former (p < 0.0001). Haemodynamic reserves were 
      11.1 +/- 2.8 and -9.6 +/- 3.0, respectively, at that time. These two parameters
      were significantly decreased just after paraparetic transient ischaemic attacks
      and two parameters in the paracentral lobule were more decreased than those in
      the anterior portion of the frontal lobe. But these increased again after
      bifrontal omental transplantation in these two regions. In summary, the watershed
      region was located anterior to the paracentral lobule before appearance of the
      transient ischaemic attacks, and widened and moved backward to include the
      paracentral lobule just before their appearance.

PMID- 7643969
TI  - Heterogeneity of GABAA-receptors: cell-specific expression, pharmacology, and
      regulation.
AB  - Vigilance, anxiety, memory, epileptogenic activity and muscle tension can be
      regulated by a modulation of GABAA-receptor function. A multitude of different
      GABAA-receptors exist in the brain due to the combinational assembly of various
      subunits encoded by at least 15 genes. The clarification of the physiological and
      pharmacological significance of GABAA-receptor subtypes, in combination with
      their cellular localization, will make it possible to identify the neuronal
      circuits regulating the respective CNS states and to provide strategies for the
      development of subtype-specific drugs for selective therapies.

PMID- 7643968
TI  - Developmental expression of N-methyl-D-aspartate (NMDA)-induced neurotoxicity,
      NMDA receptor function, and the NMDAR1 and glutamate-binding protein subunits in
      cerebellar granule cells in primary cultures.
AB  - Cerebellar granule cells maintained in vitro as primary cultures are a relatively
      homogeneous neuronal population that can be used to evaluate the developmental
      expression of neurotransmitter receptors and to assess their role in cell
      survival and degeneration. The toxicity induced by N-methyl-D-aspartate (NMDA) in
      granule cells maintained under partially depolarizing conditions and in the
      presence of physiologic extracellular concentrations of Mg2+ was greatest for the
      neurons maintained for 14 days in vitro (DIV). However, following NMDA receptor
      activation neurons as young as 5 DIV exhibited increases in the concentration of
      intracellular free Ca2+ which were as large as those achieved with cells at 8-9
      or 13-14 DIV. The less mature neurons exhibited a "down-regulation" of responses
      to increasing concentrations of NMDA and the more mature cells maintained
      elevated intracellular Ca2+ levels during the inter-stimulus periods.
      Immunochemical analyses of the expression of the NMDA receptor-associated
      proteins NMDAR1 and glutamate-binding protein (GBP) in granule cells indicated a
      developmental increase in both proteins, albeit the pattern of expression of
      NMDAR1 was the more complex. No definite correlation has yet been established
      between toxicity induced by NMDA and the expression of these two proteins.
      Finally, although the developmental expression of nitric oxide synthase, an
      enzyme that catalyzes the formation of the potentially neurotoxic radicals nitric
      oxide and superoxide anion, increased progressively with the maturation of
      neurons in culture, an inhibitor of this enzyme did not protect neurons from NMDA
      induced toxicity. Therefore, the developmental changes in granule cells that lead
      to increased vulnerability following excessive activation of NMDA receptors are
      not yet completely defined.

PMID- 7643972
TI  - New pathophysiology of Parkinson's disease revealed by posteroventral
      pallidotomy.
AB  - Since the failure of levodopa therapy to maintain long-term symptom relief in
      Parkinson's disease, posteroventral pallidotomy has seen a dramatic increase in
      use and interest. It has significantly reduced both the akinetic and hyperkinetic
      symptoms of Parkinson's disease while requiring most patients to maintain
      preoperative levodopa doses. Here we review the clinical results of over 300
      posteroventral pallidotomies and pathophysiology of Parkinson's disease in
      relationship to different neurotransmitters and medical therapy.

PMID- 7643971
TI  - Multidisciplinary treatment of cerebral arteriovenous malformations.
AB  - A series of 67 patients treated for cerebral AVM with a multidisciplinary
      approach is reported. The malformations were classified after the Spetzler
      Grading Scale, with 67% low-grade and 33% high-grade AVMs. Three modes of
      treatment were used: surgical resection, endovascular embolization, and
      radiosurgery (linear accelerator technique). The actual treatment was: surgical
      resection alone (25% of cases), embolization plus resection (25% of cases),
      embolization alone (21%) and radiosurgery (30%) either alone (12%), or after
      incomplete embolization (15%) or after incomplete resection (3%). The clinical
      outcome was evaluated in terms of deterioration due to treatment. The treatment
      was responsible for a deterioration in 28% of all patients, either minor
      deterioration (19%) neurological deficit (4%), or death (4%). All complications
      of surgical resection (17% of all operated cases) and of radiosurgery (10% of
      irradiated cases) remained minor. None was haemodynamic-related. After
      endovascular embolization, a deterioration occurred in 25% of all embolized cases
      (minor 13%, neurological deficit 5% and death 8%). These complications occurring
      after embolization were haemodynamic related: ischaemia and haemorrhage (50% for
      each mechanism). Haemorrhage occurred either during or some days after the
      embolization procedure. The angiographic eradication rate was: 80% overall, 91%
      after resection (with or without previous embolization), 87% after radiosurgery
      (alone or after other techniques), and 10% after embolization alone. The
      discussion reviews in the literature the general evolution of the management of
      cerebral AVMs, with successive application of first surgical resection, the
      embolization and lastly radiosurgery.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7643973
TI  - Embolus detection in different degrees of carotid disease.
AB  - Carotid atherosclerotic disease is a major source for artery to artery embolism.
      Stroke incidence highly depends on the degree of carotid stenosis. TCD monitoring
      for embolic signals may help to identify patients at high risk for an impeding
      stroke. This study was performed to correlate the degree of carotid stenosis with
      the occurrence of embolic signals and the clinical outcome. We performed a
      bilateral simultaneous TCD study on 4 patient groups with unilateral
      atherosclerotic disease: We studied patients with non-stenotic ICA plaques (n =
      21), 50-75% ICA stenosis (n = 20), 75-95% stenosis (n = 22), and occlusion (n =
      13). Minimum insonation time was 45 minutes. Embolic signals were not detected in
      the control group and patients with a non-stenotic ICA lesion, but in 10% of the
      patients with 50-75% stenosis, 22% of the patients with a high grade stenosis and
      39% of the patients with an ICA occlusion. There is a high specificity (92%) and
      rather low sensitivity (29%) of these microemboli for past clinical events. The
      occurrence of embolic signals correlated (p < 0.005) with a history of stroke,
      TIA or RIND. Microemboli detection may be a valuable tool to identify high risk
      patients.

PMID- 7643974
TI  - 'Morphing' class filter: an interactive tool for continuous adjustment of tissue
      type related contrast.
AB  - The proposed class filter increases tissue type related contrast in MR images of
      brain. During the first phase of the filtering process tissue type classes are
      defined. This is done by operator intervention, or by a semiautomatic process
      based either on a supervised or unsupervised classifier, respectively. During the
      second phase a pixel intensity transform makes pixels of the same tissue class
      appear 'more similar' while the pixel intensities of different classes will
      become 'more different', in effect increasing the tissue type related contrast.
      For example, normal mixture cluster analysis is performed on an MR image set
      obtained by varying pulse sequence (PS) parameters and provides unsupervised
      definition of classes while taking advantage of much greater information content
      of the whole image set in comparison to that of a single image. The algorithm
      permits continuous transition ('morphing') between the original image and the
      tissue classification image that has been calculated from the input image set by
      simple sliding cursor-bar on the computer screen under the physician's control.
      Consequently, the resulting images do not require retraining of the physician who
      is already familiar with the appearance of standard MR images and they make
      mental integration of information from a large input image set possible and
      easier.

PMID- 7643975
TI  - Anticonvulsant effect of intraventricular antiepileptic drugs. Experimental
      study.
AB  - The effect of intraventricular administration of antiepileptic drugs on an
      experimental model of epileptic seizures in rats has been investigated. Animals
      were tested in the electroshock test measuring the time duration of the tonic
      phase of the convulsion. Drugs tested were sodium phenobarbital (200-500-1000
      micrograms), phenytoin (50-100-200-500 micrograms), midazolam (100-200-500
      micrograms) and sodium valproate (500-1000-2000 micrograms), delivered via a
      catheter stereotactically placed into the lateral ventricle. Control animals were
      tested with saline. All antiepileptic drugs showed different degrees of reduction
      in the duration of the tonic phase before reaching doses that produced
      neurological symptoms. Our results demonstrate the feasibility to control
      experimental seizures by means of intraventricular injection of antiepileptic
      drugs.

PMID- 7643976
TI  - Changes in amino acid release and membrane potential during cerebral hypoxia and
      glucose deprivation.
AB  - Excessive release of glutamate is believed to play a major role in the
      susceptibility of neurons to ischaemia. Whether the glutamate release is the
      primary event or occurs in response to electrophysiologic alterations has not
      been clarified. In the present study, the amino acid release was therefore
      correlated to changes in electrophysiological parameters and energy status during
      conditions of low oxygen tension and varying glucose concentrations in rat
      hippocampal slices. Plain hypoxia failed to produce glutamate release. All
      neurons underwent, however, a slow depolarization causing most of the neurons to
      lose their membrane potential within 10 minutes. By restoring the membrane
      potential to resting level by current injection, the neurons could still be
      activated synaptically and respond to transmitter application. Following
      reoxygenation most of the cells regained their resting membrane potential, but
      showed reduced excitability. When the slices were exposed to hypoxia combined
      with glucose deprivation (simulated ischaemia), there was a pronounced increase
      in the glutamate release. This glutamate release was always preceded by a fast
      anoxic depolarization. Whereas hypoxia reduced the ATP content only to
      approximately 50%, ATP was depleted in slices exposed to simulated ischaemia. The
      results demonstrate that although the neurons lose their membrane potential
      completely during hypoxia, there is no glutamate release. A fast anoxic
      depolarization provoked by simulated ischaemia, however, is always followed by
      glutamate release, probably due to a more severe ATP depletion.

PMID- 7643977
TI  - Adenovirus-mediated p53 gene delivery inhibits 9L glioma growth in rats.
AB  - Adenoviral vectors have recently been shown to effectively deliver genes into a
      variety of tissues. Since these vectors have some advantages over the more
      extensively investigated retroviruses, we studied the effect of two replication
      defective adenovectors bearing human wild type tumor suppressor gene p53 (Adp53)
      and Escherichia coli beta-galactosidase gene (AdLacZ) on 9L glioma cells.
      Successful in vitro gene transfer was shown by DNA polymerase chain reaction
      (PCR), and expression was confirmed by reverse transcriptase RNA PCR and Western
      blot analyses. Transduction of 9L cells with the Adp53 inhibited cell growth and
      induced phenotypic changes consistent with cell death at low titers, while AdLacZ
      caused cytopathic changes only at high titers. Stereotactic injection of AdLacZ
      (10(7) plaque forming units) into tumor bed stained 25 to 30% of tumor cells at
      the site of vector delivery. Injection of Adp53 (10(7) plaque forming units), but
      not AdLacZ (controls), into established 4-day old 9L glioma brain tumors
      decreased tumor volume by 40% after 14 days. As a step toward gene therapy of
      brain tumors using replication-defective adenoviruses, these data support the use
      of tumor suppressor gene transfer for in vivo treatment of whole animal brain
      tumor models.

PMID- 7643978
TI  - Mechanical conditions of rebound of the intracranial pressure after a period of
      cerebral compression.
AB  - Brain compression of precisely defined degree and duration was produced by means
      of expansion of a supratentorial epidural balloon in anaesthetized and
      mechanically ventilated dogs. After deflation of the balloon there was a rebound
      of the intracranial pressure (ICP) to values in the range 30-89 mm Hg when
      critical thresholds of time and compression had been exceeded during the period
      of compression. A time versus cerebral perfusion pressure (CPP) graph indicated a
      CPP threshold of about 50 mm Hg and time threshold of about 6 min. Within these
      limits the critical CPP varied as a function of time. The ICP rebound had an
      approximately exponential time course with an initial rapid rise levelling off
      towards a final plateau in about 30 min. The final value was dependent on the
      time of compression but independent of the CPP. A transtentorial pressure
      gradient was induced during the compression phase and reestablished after the
      decompression when a rebound of ICP developed. Hydrostatic compression by means
      of infusion of fluid into the subarachnoid space was followed by a rebound of ICP
      in only 2/21 of the experiments in spite of time and CPP parameters which crossed
      the critical thresholds defined in the balloon compression experiments. These
      results support the hypothesis that the rebound phenomenon is related to an
      ischaemic mechanism. The difference in incidence of rebound in balloon
      compression and hydrostatic compression can probably be accounted for by a
      greater depth of ischaemia in the former case because of a direct compressive
      effect on the vascular bed by the balloon.

PMID- 7643979
TI  - Changes in brain, plasma and cerebrospinal fluid contents of beta-endorphin in
      dogs at the moment of death.
AB  - To investigate the possible participation of endogenous opioids in the cerebral
      events that take place at the moment of death we studied brain, cerebrospinal
      fluid and serum contents of beta-endorphin in dogs that were either conscious or
      unconscious at the moment of sudden death induced by cardiac arrest. Although
      with great interindividual variations, the animals that were conscious at the
      moment of cardiac arrest, presented a significant increase in beta-endorphin when
      compared with their own previous values (p < 0.05) or with the values found in
      animals that were deeply anaesthetized at the time of cardiac arrest. There seems
      to be a sudden increment of beta-endorphin in brain tissue and body fluids of
      dogs who are conscious at the moment of sudden death, this change was not
      observed in dogs that were anaesthetized prior to death. Brain opioids could
      participate in the sensations narrated by subjects in the so called near-death
      experience.

PMID- 7643980
TI  - Anterior fossa dural arteriovenous malformation discovered by means of PW-Doppler
      examination.
AB  - One case of dural arteriovenous malformation in the base of the anterior cranial
      fossa is reported. It was discovered by means of a PW-Doppler examination of
      angular branch of the ophthalmic artery in a patient under observation for
      hypertrophy of a superficial temporal artery. The nidus was located in the region
      of the cribriform plate and fed by the anterior ethmoidal arteries of both sides,
      draining into the superior sagittal sinus, via pial enlarged veins. The patient
      successfully underwent surgical treatment and a post-operative PW-Doppler
      confirmed normalization of the flow pattern in the angular branches of both
      ophthalmic arteries.

PMID- 7643981
TI  - A teratocarcinoma developing after gross total excision of a pineal teratoma in a
      patient with systemic lupus erythematosus.
AB  - This is a rare case of a teratocarcinoma developing at the same site one year
      after the gross total excision of a mature pineal teratoma. The malignant tumour
      arose probably from microscopic remnants of the teratoma. This patient also
      suffered from systemic lupus erythematosus. Autoimmune diseases have been
      associated with an increased risk of malignancy, and in this case may have
      contributed to the malignant transformation of the teratoma.

PMID- 7643982
TI  - Myopathological findings in interstitial myositis in type II polyendocrine
      autoimmune syndrome (Schmidt's syndrome).
AB  - We report on a patient with an interstitial myositis in type II polyendocrine
      autoimmune disease (Schmidt's syndrome) showing an immunohistochemical
      demonstrated perifascicular expression of Leu 19 indicating perifascicular
      denervation, which could not be detected with classical histological methods. In
      neurogenic muscular atrophy, idiopathic polymyositis and normal muscle we could
      not find such an exclusive perifascicular expression of the Leu 19 antigen. We
      conclude that perifascicular denervation is a characteristic feature in IM and
      thus might have diagnostic value. Furthermore the interstitial myositis is
      characterized by a complement-mediated angiopathy (vascular deposition of the
      membranolytic attack complex C5b-9). This pattern is comparable to well-known
      changes in dermatomyositis. Interstitial myositis and dermatomyositis are
      evidently pathogenetically similar according to myopathological criteria, but
      show phenotypic differences. Additional in interstitial myositis and idiopathic
      polymyositis inflammatory infiltrates surrounding Leu 19 expressing myocytes are
      regarded as the cause of disseminated intrafascicular muscle fibre denervation.

PMID- 7643983
TI  - Management strategies and surgical techniques for deep-seated supratentorial
      arteriovenous malformations.
AB  - The therapeutic options for arteriovenous malformations (AVMs) of the thalamus
      and the basal ganglia have expanded to include preoperative embolization,
      stereotactic radiation, and microsurgery. Adjuncts to surgery such as
      stereotactic guidance, electrophysiological monitoring, intraoperative
      ultrasound, intraoperative angiography, and induced hypotension have
      significantly reduced postoperative morbidity. We review the management and
      outcome of 65 consecutive patients who were treated for deep-seated
      supratentorial vascular malformations; 45 patients (69%) were treated surgically,
      10 patients (15%) were treated conservatively, and 10 patients (15%) underwent
      radiosurgery. This retrospective study (1976-1993) includes 51 AVMs (78%), 14
      cavernous angiomas (22%), and 10 associated vascular anomalies (15%). Initially,
      59 (91%) of 65 patients presented with hemorrhage; 23 patients (39%) suffered
      recurrent hemorrhages. Malformations ranged in size from 1 to 7.5 cm (mean, 2.8
      cm). AVMs were fed principally by the anterior and posterior choroidal,
      thalamoperforate, and lenticulostriate arteries. Venous drainage was uniform via
      the deep venous system. Among 39 patients who underwent surgery for AVMs, 26
      (67%) improved, 7 (18%) remained unchanged, 5 (13%) worsened, and 1 (3%) died.
      Among six patients who underwent surgery for cavernous angiomas, four (66%)
      improved, one (17%) remained unchanged, and one (17%) worsened. Operative
      complications included transient neurological deficits in seven patients (16%),
      permanent neurological deficits in six patients (13%), and new bleeding from
      residual AVMs in four patients (9%). Among 10 patients treated conservatively, 3
      (30%) had repeat hemorrhages, 2 (20%) had progressive neurological deficits, and
      1 (10%) died.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7643984
TI  - Morphological changes in human cerebral arteries after percutaneous transluminal
      angioplasty for vasospasm caused by subarachnoid hemorrhage.
AB  - Light and electron microscopy were used to study morphological changes in
      cerebral arteries after percutaneous transluminal angioplasty (PTA) for vasospasm
      in two patients with aneurysmal subarachnoid hemorrhage. One patient died of
      gastric bleeding 5 days after PTA. Postmortem examination of the inflated middle
      cerebral arteries revealed heterogeneously extended walls and dilated lumina.
      Throughout the vessel walls, the extracellular matrix, which was composed of
      nonmuscle components such as increased collagen, was stretched in conjunction
      with the medial muscle component. Also, torn and thinned areas of the wall and
      intramural hemorrhages were caused by overinflation. The second patient died of
      massive cerebral infarction caused by diffuse vasospasm 5 days after PTA.
      Prominent stretching of the walls at the atheromatous plaque margin in the
      dilated vessel was found in addition to the morphological changes observed in the
      first patient. These observations suggest that characteristic pathological
      alterations might be present in the vessel wall at the site of angioplasty. The
      major mechanism of the long-lasting effects of PTA seems to be the stretching and
      disruption of both the degenerative muscle and the proliferative nonmuscle
      components, mainly in the media of the vasospastic vessels.

PMID- 7643985
TI  - Diaphragma sellae meningiomas.
AB  - Despite their unique clinical, radiological, and surgical considerations,
      diaphragma sellae meningiomas remain largely undistinguished from tuberculum
      sellae meningiomas. On the basis of our experience with 12 patients with
      diaphragma sellae meningiomas and our review of the literature, we classify these
      tumors into three groups: Type A, originating from the upper leaf of the
      diaphragma sellae anterior to the pituitary stalk; Type B, originating from the
      upper leaf of the diaphragma sellae posterior to the pituitary stalk; and Type C,
      originating from the inferior leaf of the diaphragma sellae. Each type has
      specific clinical symptoms. Type A mainly presents with unilateral visual
      disturbances and visual field defects resembling those of tuberculum sellae
      meningiomas, although preoperative diabetes insipidus occurred in patients with
      large tumors. Type B causes fewer visual disturbances, but memory disturbance and
      hypopituitarism occur. Type C closely resembles nonfunctioning pituitary
      adenomas; bitemporal hemianopsia and hypopituitarism are common. Multiplanar
      magnetic resonance images can accurately diagnose the tumor and establish its
      type. Surgical approaches include the cranio-orbital approach for Types A and B
      and the transcranial-transsphenoidal approach for Type C. Surgery is more
      difficult than for tuberculum sellae meningiomas because of the deep location and
      the difficulty of dissecting Types A and B from the pituitary stalk. Repair of
      the sphenoid sinus to prevent cerebrospinal fluid leakage is mandatory for Type C
      tumors.

PMID- 7643986
TI  - The applicability of Collins' Law to childhood brain tumors and its usefulness as
      a predictor of survival.
AB  - In 1955, Collins made the observation that tumor recurrence in children with
      Wilms' tumor was correlated with the child's age plus 9 months. This concept of a
      period of risk for recurrence was later applied to a variety of tumors in
      children and became known as Collins' Law (CL). The law has been a successful
      predictor of survival for some children with neural tumors within the central
      nervous system and a poor predictor for others. We tested Collins' concept of a
      period of risk for recurrence and extended it to survival for 14 childhood neural
      tumors described in the Childhood Brain Tumor Consortium (CBTC) database. The
      CBTC data describe clinical, surgical, and histological details (over a 49-year
      period in 10 institutions) from 3921 patients under the age of 21 years at the
      time of their first surgical procedure for a brain tumor. CL was considered to be
      a good predictor of survival if fewer than 10% of patients who die survive beyond
      the expiration of the period of risk for that child. We found that CL applied to
      tumors such as anaplastic astrocytoma, glioblastoma, pineoblastoma,
      medulloblastoma or "primitive neuroectodermal tumor," teratoma, and germinoma, as
      well as ependymoma, papilloma, and tumors that could not be classified; it had no
      predictive value in craniopharyngioma, oligodendroglioma, or plain, fibrillary,
      pilocytic, or protoplasmic astrocytoma. We had sufficient follow-up data to
      determine adherence to CL when the child's age at diagnosis was less than 8
      years; it is likely that CL applies to older children with these tumors, but we
      did not have the data to show this unequivocally.

PMID- 7643988
TI  - Prognostic factors of spinal cord stimulation for chronic back and leg pain.
AB  - Spinal cord stimulation (SCS) has been used for more than 20 years in the
      treatment of diverse pain conditions. Although recent studies have identified
      more clearly those conditions for which SCSoffers a favorable prognosis, the
      identification of a patient population in whom reasonably long-term success can
      be expected has been difficult. In an effort to improve patient selection and
      increase the overall success rate of treatment, we have examined various
      physical, demographic, and psychosocial variables as predictors of SCS outcome.
      The study population consisted of 40 patients with chronic low back and/or leg
      pain, 85% of whom were diagnosed with failed back surgery syndrome. Medical
      history and demographic data were collected as part of an initial assessment
      along with patient responses to the Minnesota Multiphasic Personality Inventory,
      the visual analogue pain rating scale (VAS), the McGill Pain Questionnaire, the
      Oswestry Disability Questionnaire, the Beck Depression Inventory, and the
      Sickness Impact Profile. Treatment outcomes were examined and found to improve
      significantly after 3 months of stimulation. Subsequent regression analysis
      revealed that patient age, the Minnesota Multiphasic Personality Inventory
      depression subscale D, and the evaluative subscale of the McGill Pain
      Questionnaire (MPQe) were important predictors of posttreatment pain status.
      Increased patient age and D subscale scores correlated negatively with pain
      status, as measured by the percentage of changes in pretreatment and
      posttreatment VAS scores, % delta VAS. In contrast, higher MPQe correlated with
      improved pain status. By the use of the following equation and the definition
      commonly associated with SCS success (at least 50% decrease in the VAS pain
      level), the success or failure of 3 months of SCS was correctly predicted in 88%
      of the study population. Our results suggest that patient age, Minnesota
      Multiphasic Personality Inventory depression, and MPQe may be clinically useful
      in the prediction of pain status after 3 months of SCS in patients with chronic
      low back and/or leg pain. % delta VAS = 112.57 - 1.98 (D)-1.68 (Age) + 35.54
      (MPQe).

PMID- 7643989
TI  - Ventroposterior medial pallidotomy in patients with advanced Parkinson's disease.
AB  - In a preliminary study, the effects of ventroposterior medial pallidotomy were
      evaluated in five patients with advanced Parkinson's disease in whom medical
      therapy had failed. The mean age was 67.0 +/- 5.6 years, and the mean Hoehn and
      Yahr stage when "off" was 3.9 +/- 1.3. Three patients received unilateral
      pallidotomies; two of these received another pallidotomy after 8 weeks. Two other
      patients received staged bilateral pallidotomies. No significant differences in
      overall function could be seen before and after the first surgical procedure. All
      three patients with peak-dose dyskinesias or dystonia had marked contralateral
      reduction in these symptoms. Ventroposterior medial pallidotomy can ameliorate
      peak-dose dyskinesias in patients with advanced Parkinson's disease. Overall
      function improvement is not remarkable.

PMID- 7643987
TI  - Impact of cranioplasty on headache after acoustic neuroma removal.
AB  - We reported previously the incidence of headache after the retrosigmoid removal
      of an acoustic neuroma as 23% at 3 months, declining to 9% at 2 years after
      surgery. In an attempt to reduce the incidence and the severity of these
      headaches, we made one change in our surgical procedure, which was to perform a
      cranioplasty with methyl methacrylate. Twenty-four patients underwent the
      cranioplasty and were followed for at least 3 months postoperatively. These
      patients were matched to 24 patients who did not undergo a cranioplasty. We found
      a 4% incidence of headache in the cranioplasty group and a 17% incidence in the
      matched group. No complications were related to this change in our procedure.

PMID- 7643990
TI  - The results, indications, and physiology of posteroventral pallidotomy for
      patients with Parkinson's disease.
AB  - In the past, stereotactic surgical intervention for Parkinson's disease was
      considered indicated only in those patients with active motor manifestations that
      were refractory to pharmacological therapy, manifestations such as tremor,
      rigidity, dystonia, and dyskinesia. With the reintroduction and refinement of
      Leksell's posteroventral pallidotomy, both akinetic and hyperkinetic symptoms are
      now amenable to surgical treatment. We have analyzed the results of 126 patients
      who underwent either unilateral (n = 58) or bilateral (n = 68) posteroventral
      pallidotomies. The Unified Parkinson's Disease Rating Scale and Hoehn and Yahr
      Staging Scale were used for preoperative and postoperative objective assessments.
      Postoperative follow-up evaluation occurred initially at 1 week and subsequently
      at intervals between 1 and 12 months (mean = 4.5 months) after surgery. Although
      individual motor subscores on the Unified Parkinson's Disease Rating Scale were
      significantly reduced (n = 126, P < or = 0.01), the most dramatic findings were
      the reversal of akinetic symptoms and the elimination of dyskinesia and profound
      "off" periods. These clinical results, combined with intraoperative
      microelectrode records revealing pallidal neuronal hyperactivity, suggest a
      reconsideration of the pathophysiology of akinesia and point to possible
      mechanisms of akinesia improvement by posteroventral pallidotomy in some
      parkinsonian subgroups.

PMID- 7643991
TI  - Endoscope-assisted craniotomy: approach to the rostral brain stem.
AB  - We describe a surgical technique to improve visualization of deep brain
      structures during craniotomy. The technique, developed in a cadaveric model,
      combines the use of an operating microscope and a solid-rod lens endoscope.
      Addition of the endoscope during craniotomy allows the operator to visualize
      structures that otherwise might not have been seen. An approach to the brain stem
      is demonstrated.

PMID- 7643992
TI  - Lumbar discectomy: use of an epidural morphine sponge for postoperative pain
      control.
AB  - A technique for extended ambulatory epidural pain control after lumbar discectomy
      is described; preliminary results with 45 patients are reported; and alternative
      methods of narcotic analgesia are reviewed. In this technique, an absorbable
      gelatin sponge (Gelfoam, Upjohn Co., Kalamazoo, MI) is contoured to the
      laminotomy defect, placed in methylprednisolone acetate (40-80 mg), and then
      injected with 2 to 4 mg of preservative-free morphine (a small needle was used to
      fill the sponge). The sponge is placed over the defect before closure. A review
      of office and hospital records was conducted. The series consisted of 33 men and
      12 women (mean age, 39 yr; range, 24-57 yr); records showed narcotic use in 34
      patients (parenteral in 3) and work-related injuries in 14 patients. Thirty-three
      patients were ambulatory postoperatively on the day of surgery; all were
      ambulatory by postoperative day (POD) 1. On the day of surgery, 18 patients did
      not require any postoperative analgesics; on POD 1, 22 patients did not require
      analgesics. Six patients received parenteral narcotics; four received one dose
      only, and two had two or more doses. Thirty-one patients were discharged from the
      hospital on POD 1, and 10 were discharged POD 2. The other patients were
      discharged from the hospital on POD 3 (three patients) or POD 4 (one patient).
      When they were discharged, all patients received a limited supply of
      acetaminophen with codeine for pain control at home. After discharge, phone
      follow-up (at 1 week) and office follow-ups (at 3-5 weeks) revealed only one
      patient with more than mild discomfort. Three patients required one-time bladder
      catheterization, and one patient had presumed discitis 1 month postoperatively.
      In a control group who had undergone surgery 3 months previously, the average day
      of discharge had been POD 3.07; no control patient had been discharged on POD 1,
      and only 20% had been discharged on POD 2. This method provides effective, safe,
      and extended analgesia after lumbar discectomy.

PMID- 7643993
TI  - Clinical evaluation of a miniature strain-gauge transducer for monitoring
      intracranial pressure.
AB  - In 25 patients, we evaluated the accuracy of a new miniature strain-gauge
      transducer developed for the measurement of intracranial pressure (ICP). The ICP
      in each patient was measured with the intraventricular, miniature strain-gauge
      transducer, and that value was compared with the ICP measured with a
      ventriculostomy catheter coupled to an external strain-gauge transducer. From the
      two monitors, 2218 simultaneous measurements of ICP were obtained. The average
      ICP measured with the miniature strain-gauge transducer was 15.9 +/- 10.0 mm Hg
      (range, -3 to 104 mm Hg). The ICP measured with the ventriculostomy-catheter
      transducer averaged 15.4 +/- 10.1 mm Hg (range, -9 to 104 mm Hg). A highly
      significant correlation was found over the wide range of pressures observed (n =
      2218, r = 0.97, P < 0.001). The average difference between the two measurements
      of the ICP was 0.5 +/- 2.6 mm Hg, and the differences were equally positive and
      negative, demonstrating no consistent bias. The two values for the ICP were
      within 2 mm Hg of each other on 63% of the measurements and within 4 mm Hg of
      each other on 89% of the measurements. The average zero drift of the miniature
      strain-gauge transducer, measured at ambient pressure after removal of the
      catheter, was 0.2 +/- 0.5 mm Hg. The results indicate that this miniature strain
      gauge transducer is highly accurate and stable and that it is a reliable
      alternative to a ventriculostomy for monitoring the ICP.

PMID- 7643994
TI  - The evaluation of the wave-form analysis capability of a new strain-gauge
      intracranial pressure MicroSensor.
AB  - Both laboratory and clinical trials have indicated the reliability of a new
      catheter-tip, strain-gauge intracranial pressure transducer. We report on the
      results of bench tests comparing the wave-form analysis capabilities of the new
      Codman intracranial pressure MicroSensor and a similar strain-gauge transducer.
      Good agreement was found between the two sensors with no significant nonlinearity
      or hysteresis over a measured pressure range from 0 to 100 mg Hg. Under "fluid
      filled" conditions, the MicroSensor showed good reproduction of an arterial
      pressure wave form; when spectral analysis was used to analyze the two sensor
      types and break them down into harmonic components, no significant differences
      could be found for any of the first 10 amplitude and phase harmonics. If proven
      to stay robust after long-term clinical use, this sensor may be a useful
      alternative to the existing transducer systems for routinely monitoring the
      intracranial pressure and its wave form.

PMID- 7643995
TI  - Biomechanical effects of transoral odontoidectomy.
AB  - The acute biomechanical effects of transoral odontoidectomy were studied by using
      qualitative and quantitative methods to assess atlantoaxial motion. In vitro
      biomechanical testing was performed on the upper cervical spines of eight baboon
      and five human cadaveric specimens. Using an unconstrained testing apparatus, we
      performed a flexibility method of testing. Physiological range loading was
      applied to atlantoaxial specimens, and three-dimensional motion was analyzed with
      stereophotogrammetry. Force-deformation relationships were delineated in intact
      specimens and again after surgical removal of the anterior C1 arch, odontoid
      process, and transverse atlantal ligament. We studied the total range of
      rotational and linear motions, the behavior of the neutral zone and elastic zone,
      the flexibility coefficients, and the instantaneous axes of rotation during
      flexion, extension, bilateral lateral bending, and bilateral axial rotation.
      Odontoidectomy produced several distinct alterations in motion and in force
      deformation responses at C1-C2 that were almost identical in the baboon and human
      specimens. After odontoidectomy, the atlas developed significantly increased
      translational movements, which were most prominent in the anteroposterior
      direction. The total angular range of motion increased significantly during
      flexion, extension, and lateral bending but not during axial rotation. When the
      total range of motion was altered, the neutral zone was affected selectively and
      the elastic zone was spared. Surgery produced mobile, widely spread,
      unconstrained instantaneous axes of rotation that were in a constrained, fixed
      position in intact specimens. Clinically, transoral odontoidectomy may predispose
      patients to spinal instability. Even if acute spinal instability is not apparent,
      the patients may be susceptible to the delayed effects of the surgery because of
      the altered anatomy and biomechanical responses.

PMID- 7643996
TI  - Pallidotomy in Parkinson's disease.

PMID- 7643997
TI  - In vitro and in vivo variation in transferrin receptor expression on a human
      medulloblastoma cell line.
AB  - The poor prognosis associated with pediatric central nervous system tumors such
      as medulloblastoma has led to the development and investigation of a variety of
      new treatment techniques. Therapeutic agents include targeted-toxin conjugates or
      immunotoxins that show significant in vitro activity against many brain tumors.
      Transferrin receptors (TRs) are specific, cell-surface antigens that are
      expressed preferentially on brain tumors rather than on normal human brain
      tissue. This antigen has been successfully targeted in human and nonhuman brain
      tumors in vitro and in vivo. In this study, when TRs were used as a target in the
      DAOY human medulloblastoma-derived cell line in vitro, a significant level of
      expression was confirmed by testing the sensitivity to different immunotoxins. To
      ensure the relevance of the in vitro data to the in vivo situation, we also
      analyzed TR expression in DAOY tumors growing in athymic mice and rats.
      Immunocytochemistry, immunohistochemistry, immunobead binding,
      immunofluorescence, 125iodine-transferrin binding, and Northern blot analysis
      were used to compare TR expression in DAOY cells in vitro and in vivo. All in
      vitro assays demonstrated significant TR expression, whereas in vivo, the TR
      expression was negligible in the DAOY tissue. The results caution against
      extrapolating in vitro antigen and receptor expression data directly to the in
      vivo situation. Using a transferrin-toxin conjugate in a nude rat model of
      leptomeningeal carcinomatosis, we achieved therapeutic efficacy, despite
      demonstrating reduced TR expression on tumor tissue. With respect to clinical
      efficacy, the reduced expression of TR on DAOY medulloblastoma in vivo may be
      less significant than expected because of the extreme potency of immunotoxins
      observed in central nervous system tumors.

PMID- 7643998
TI  - Modification of human glioma locomotion in vitro by cytokines EGF, bFGF, PDGFbb,
      NGF, and TNF alpha.
AB  - Cytokines exert receptor-mediated control over glia. Up-regulation of receptor
      expression of cytokine production corresponds with the acquisition of a
      neoplastic phenotype. A modified radial dish assay was used to determine whether
      in vitro locomotion of glioma cells is modified by the epidermal growth factor,
      the basic fibroblast growth factor, the bb dimer of platelet-derived growth
      factor, the nerve growth factor, or the tumor necrosis factor alpha. Human glioma
      cells were plated in the center of a petri dish with one of these cytokines in
      0.5 ml agar (50 ng/ml if the cytokine was distributed evenly throughout the dish)
      at one edge, and 0.5 ml plain agar at the opposite edge. After 24 hours, a
      central zone of cells was established; the agar was gelatinized. Feeding medium
      was added to the dish, and slow elution from the agar established a cytokine
      gradient. Cell counts were performed daily over 6 to 10 days at predetermined
      distances on both sides of the central zone to assess directional cellular
      movement with respect to the cytokine gradient and the plain agar. The epidermal
      growth factor caused continuous chemoattraction, whereas the tumor necrosis
      factor alpha caused slight chemorepulsion for 24 to 48 hours, followed by strong
      chemoattraction. The bb dimer of platelet-derived growth factor, the basic
      fibroblast growth factor, and the nerve growth factor all maintained
      chemorepulsion over the entire 6 to 10 days. Therefore, the cytokines did affect
      glioma cell motility in vitro, and the modified radial dish assay used in this
      study provided a useful in vitro model for assessing the impact of the cytokines
      on glioma cell locomotion.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7643999
TI  - Delayed tissue-plasminogen activator therapy in a rabbit model of thromboembolic
      stroke.
AB  - This study investigated the efficacy and safety of delayed therapy with tissue
      plasminogen activator (t-PA) in a rabbit model of thromboembolic stroke. The t-PA
      therapy was started 3, 4, or 5 hours after autologous clot embolization. New
      Zealand rabbits were randomized to receive a 2-hour intravenous infusion of
      either t-PA (6.3 mg/kg) or a saline solution (0.9% saline) after an autologous
      clot had embolized the anterior cerebral circulation. Regional cerebral blood
      flow (rCBF), intracranial pressure (ICP), and infarct size were measured to
      determine the effects of the delayed administration of the t-PA after
      intracranial embolization. Additionally, the following physiological parameters
      were monitored throughout the protocol: mean arterial pressure, hematocrit,
      arterial blood gases, glucose, and core and brain temperatures. All animals were
      studied for 4 hours after the administration of the t-PA or control solution;
      thus, the duration of each experiment was 7, 8, or 9 hours after autologous clot
      embolization. In control animals, brain infarct size and final ICP values were
      directly related to the length of time studied after clot embolization; among
      control animals, the largest infarct size and greatest rise in ICP were seen 9
      hours after embolization.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7644000
TI  - The time course of myosin light-chain phosphorylation in blood-induced vasospasm.
AB  - The phosphorylation of an M(r) 20,000 myosin light chain (MLC20) promotes the
      generation of contractile force through actin-myosin adenosine triphosphatase in
      most agonist-mediated vascular smooth muscle cell contraction. However, the role
      of calcium-mediated contractile processes in sustained arterial narrowing after
      subarachnoid hemorrhage remains unknown. In a femoral artery model of vasospasm,
      whole blood was applied to arteries in 54 rats for periods of 2 to 10 days; the
      contralateral artery treated with platelet-rich plasma served as matched control.
      During the early stage of vasospasm (Days 2-5), in the media of arteries exposed
      to blood, MLC20 phosphorylation (including diphosphorylated forms) increased
      significantly (30-38%; P < 0.05); total medial MLC20 during this interval was
      comparable to that in controls. After 5 days, however, total MLC20 decreased
      markedly (> 90%; P < 0.01) compared with controls; phosphorylated MLC20 was
      undetectable during this interval. MLC20-mediated contractile processes may be
      prominent in the early stages of arterial narrowing after subarachnoid
      hemorrhage; later stages are associated with the loss of MLC20 and the possible
      persistence of arterial narrowing by other mechanisms.

PMID- 7644002
TI  - Radiation therapy for sarcoid of the thalamus/posterior third ventricle: case
      report.
AB  - There are a limited number of previously reported cases involving the use of
      radiation therapy for sarcoid of the brain. The case of a 22-year-old man with a
      thalamic/posterior third ventricle sarcoid mass that grew despite steroid
      medication is presented. The patient was treated with external beam radiation to
      a total dose of 20 Gy, with 2-Gy fractions over 14 elapsed days. A complete
      radiographic response was achieved 4 months after radiation was completed.
      Radiographic follow-up through 8 months postradiation shows no evidence of
      disease recurrence. Fractionated radiation therapy in low-to-moderate doses
      appears to be efficacious in steroid-refractory sarcoid of the brain.

PMID- 7644001
TI  - Rosai-Dorfman disease mimicking multiple meningioma: case report.
AB  - Rosai-Dorfman disease is a rare idiopathic histioproliferative disease affecting
      the lymph nodes. Extranodal involvement has also been recognized, but central
      nervous system manifestations are extremely rare. Only 12 patients with
      intracranial involvement have been reported previously, and they all presented
      with clinical and radiological findings suggestive of meningioma. We report
      multiple meningeal nodules in a patient presenting with seizures whose
      pathological findings at surgery confirmed the diagnosis of Rosai-Dorfman
      disease. A review of all previously reported intracranial lesions is presented.

PMID- 7644003
TI  - Ossifying fibroma involving the paranasal sinuses, orbit, and anterior cranial
      fossa: case report.
AB  - We report a case of ossifying fibroma involving the paranasal sinuses, orbit, and
      anterior cranial fossa. Ossifying fibroma is a benign fibro-osseous tumor, rarely
      involving the anterior cranial base. The patient was admitted because of
      exophthalmos and diplopia. The lesion was totally removed surgically. Grossly, it
      had a thin osseous capsule. The microscopic examination showed mainly fibrous
      tissues and lamellar bone trabeculae rimmed by osteoblasts and myxomatous areas
      in some parts. The histopathological aspect of this entity is discussed with
      reference to the differential diagnosis from monostotic fibrous dysplasia.

PMID- 7644004
TI  - Multicentric infantile myofibromatosis in the cranium: case report.
AB  - Infantile myofibromatosis is a rare clinical entity characterized by multiple
      mesenchymal tumors in the neonatal period. We describe a 15-month-old girl with
      multicentric cranial lesions involving the parietal and occipital bones
      associated with a single small subcutaneous lesion in the back. Magnetic
      resonance imaging clearly demonstrated the isointense lesions on T1-, T2-, and
      proton density-weighted images, which showed marked gadolinium enhancement of the
      tumors and adjacent dura mater. A histological examination of the resected
      temporal lesion revealed the myofibroblastic nature of the tumor cells. This is
      the first description of magnetic resonance features of multicentric infantile
      myofibromatosis in the cranium, and gadolinium-enhanced magnetic resonance images
      were useful in showing dural involvement. The importance of recognizing this
      disorder is emphasized because of its special clinical behavior.

PMID- 7644005
TI  - Solitary T-cell lymphoma of the sciatic nerve: case report.
AB  - In lymphoproliferative disorders, primary involvement of the peripheral nerve is
      rare. This report describes a very rare case of a solitary extranodal T-cell
      lymphoma of the sciatic nerve. Magnetic resonance imaging and gallium
      scintigraphy were useful for the identification of the lesion of the sciatic
      nerve. The histological analysis of an open-biopsy specimen disclosed a T-cell
      lymphoma (non-Hodgkin's lymphoma, lymphoblastic type). Radiotherapy and
      chemotherapy resulted in a partial regression of the disease.

PMID- 7644006
TI  - Solitary dural plasmacytoma: case report.
AB  - Solitary intracranial plasmacytomas are exceedingly rare. Before this case
      report, only 14 cases of solitary dural and 4 cases of intracerebral
      plasmacytomas had been reported in the literature. We present a case of solitary
      plasmacytoma originating from the right frontal dura mater in a 52-year-old man;
      we also review the literature on the previous cases. To our knowledge, our
      patient is the first patient with a solitary dural plasmacytoma to be examined
      with magnetic resonance imaging.

PMID- 7644007
TI  - Interhemispheric subdural hematoma in adults: case reports and a review of the
      literature.
AB  - The interhemispheric subdural hematoma is a relatively uncommon type of subdural
      hematoma, especially seen in patients with blood clotting disturbances. When its
      mass becomes sufficiently large, specific neurological abnormalities such as
      hemiparesis and signs of the falx syndrome are seen. Treatment can consist of
      conservative observation or craniotomy and is dictated by the clinical course.
      Conservative management is the treatment of choice for patients without
      disturbances of consciousness and for patients with stable clinical conditions.
      Surgical treatment is necessary in patients with progressive deterioration. Three
      case reports are presented, as well as a review of 64 cases described in the
      literature. The salient aspects of this clinical entity are discussed.

PMID- 7644008
TI  - Subperiosteal, subperiorbital dissection and division of the anterior and
      posterior ethmoid arteries for meningiomas of the cribriform plate and planum
      sphenoidale: technical note.
AB  - Removal of meningiomas from the region of the cribriform plate and the planum
      sphenoidale may entail a bifrontal craniotomy and an interruption of the tumor's
      blood supply along the floor of the anterior cranial base. However, with this
      approach, the presence of bulky tumor above makes it difficult to control
      bleeding from multiple bony foramina in the anterior cranial base and to expose
      these foramina. The blood supply to the dura in this region, and, therefore, to
      these tumors, is predominantly from the anterior and posterior ethmoid arteries.
      Preoperative embolization of ethmoid arteries is not without a significant and
      prohibitive risk of blindness. A frontoethmoidal approach to the arteries on both
      sides requires two separate skin incisions. Therefore, a subperiosteal,
      subperiorbital dissection and division of these arteries via a bicoronal skin
      incision is a practical alternative.

PMID- 7644009
TI  - Mastoid canal and migrated bone wax in the sigmoid sinus: technical report.
AB  - A study of the migration of bone wax into the sigmoid sinus through the mastoid
      canal is reported here. In 7 of 161 patients who underwent retromastoid
      craniectomy, the postoperative soft tissue window image computed tomographic
      scans demonstrated a hypodense mass in the ipsilateral sigmoid sinus. The density
      value of the hypodense mass ranged from -34 to -79 Hounsfield units, which was
      neither as low as that of air nor as high as that of cerebrospinal fluid, but was
      comparable to that of fat tissue or bone wax. The continued presence of all of
      these masses in the sigmoid sinus was confirmed 1 month to 2 years after surgery.
      These computed tomographic findings suggested that this abnormal hypodense mass
      might be a migrated fragment of the bone wax that had been used for the control
      of venous bleeding from the mastoid emissary vein, because each of the seven
      affected patients had a large mastoid foramen and a large quantity of bone wax
      had been needed to control the bleeding during retromastoid craniectomy. No other
      material with the potential to migrate into the sigmoid sinus had been applied as
      a packing material. In two of the seven patients, venous magnetic resonance
      angiography after surgery demonstrated that the ipsilateral sigmoid sinus was not
      patent and the computed tomographic scans also revealed that the hypodense masses
      occupied the sigmoid sinus. It is concluded that the intrasurgical application of
      a large quantity of bone wax to control the bleeding from the large emissary
      veins carries a risk of the migration of bone wax into the sigmoid
      sinus.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7644010
TI  - Delayed parent artery narrowing occurring months after aneurysm surgery: a
      complication after aneurysm surgery--technical case report.
AB  - The authors report two patients with a rare complication of parent artery
      narrowing that occurred 3 and 6 months after aneurysm surgery. In both cases, the
      stenosed arteries had been wrapped around their entire circumferences with
      neurosurgical sponge (cotton linter) and coated with plastic adhesive
      (cyanoacrylate compounds) and the aneurysmal neck had been clipped. This
      reinforcement procedure was considered to have caused the unusual delayed
      arterial narrowing. The importance of avoiding circumferential parent artery
      wrapping with plastic-adhesive coating is emphasized.

PMID- 7644011
TI  - Combined extracranial-intracranial bypass and intraoperative balloon occlusion
      for the treatment of intracavernous and proximal carotid artery aneurysms.

PMID- 7644012
TI  - Arteriovenous malformation draining vein physiology and determinants of
      transnidal pressure gradients.

PMID- 7644013
TI  - Mannitol, intracranial pressure and vasogenic edema.

PMID- 7644014
TI  - Frontoethmoidal osteoma complicated by intracranial mucocele and hypertensive
      pneumocephalus: case report.

PMID- 7644015
TI  - Intraoperative monitoring of the vagus nerve during intracranial glossopharyngeal
      and upper vagal rhizotomy: technical note.

PMID- 7644016
TI  - GABA and GABAA receptor changes in the substantia nigra of the rat following
      quinolinic acid lesions in the striatum closely resemble Huntington's disease.
AB  - GABA and GABAA receptors have been studied in the substantia nigra of the rat
      following quinolinic acid lesions in the striatum. The regional distribution of
      GABA and GABAA receptors was investigated using immunohistochemical techniques
      with monoclonal antibodies to GABA and to the beta 2.3 subtypes of the GABAA
      receptor complex. The distribution, density and cellular localization of GABAA
      receptors were studied using quantitative receptor autoradiography and 6
      hydroxydopamine-induced degeneration of dopaminergic pars compacta neurons. The
      subunit configuration of GABAA receptors was investigated using in situ
      hybridization histochemistry and subunit subtype-specific oligonucleotide probes.
      The results showed that in the normal substantia nigra GABA and GABAA receptors
      were mainly localized within the pars reticulata. GABAA receptors were mainly of
      the BZI variety, had a subunit subtype configuration that included alpha 1 and
      beta 2.3 subtypes, and showed a rostrocaudal gradient in the density of
      receptors; the density of receptors in the caudal third was 56% higher than that
      in the rostral third of the pars reticulata. Following quinolinic acid-induced
      degeneration of the striatonigral pathway, there was a marked loss of GABA
      immunoreactivity and a 59% increase in the density of GABAA receptors in the
      substantia nigra pars reticulata. There was a corresponding regional topography
      in the pattern of loss of GABA immunoreactivity and in the pattern of increase in
      GABAA receptors in the pars reticulata; the topography varied with the size and
      placement of the lesion in the striatum and correlated with the known
      topographical organization of the striatonigral projection. The quantitative
      autoradiographic results showed that following quinolinic acid lesions in the
      striatum: (i) the greatest increase in the density of GABAA receptors occurred in
      the middle third (91% increase) of the pars reticulata; (ii) the receptors were
      mainly of the GABAA/BZI variety; and (iii) 6-hydroxydopamine-induced degeneration
      of the dopaminergic pars compacta neurons did not significantly affect the
      density of receptors, indicating that the increased receptor binding was mainly
      localized on non-dopaminergic pars reticulata neurons. The immunohistochemical
      and in situ hybridization studies showed that, as in the normal substantia nigra,
      GABAA receptors in the substantia nigra pars reticulata on the lesioned side
      contained the alpha 1 and beta 2.3 GABAA receptor subtypes; the alpha 1 and beta
      2.3 subtypes (but not the alpha 2) were increased after quinolinic acid
      lesions.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7644017
TI  - Heterogeneous and compartmental distribution of zinc in the striatum and globus
      pallidus of the rat.
AB  - The distribution of vesicular or chelatable zinc was analysed in the dorsal and
      ventral subdivisions of the striatum and globus pallidus of the rat with
      Danscher's selenium method. Acetylcholinesterase and Calbindin-D28k were used as
      striatal and pallidal markers in order to analyse the possible
      compartmentalization of the distribution of zinc in the striatum and globus
      pallidus. The main findings of this study are the following: (1) The distribution
      of vesicular zinc in the dorsal striatum was heterogeneous. A peripheral rim of
      tissue heavily stained for zinc was detected in the medial, dorsal and lateral
      striatal areas, along most of the rostrocaudal extent of the striatum. addition,
      patch-like zones intensely stained for zinc were prominent in the rostral half of
      the caudate-putamen complex. (2) In some regions of the rostral half of the
      caudate-putamen complex, the staining for zinc appeared to follow the well-known
      striatal patches (striosomes)/matrix organization. However, in other regions of
      the rostral half of the striatum such a relation was not detected. (3) The
      ventral striatum also showed a heterogeneous staining for zinc. Thus, in the most
      ventral part of the caudate-putamen complex, both subdivisions of the nucleus
      accumbens and parts of the olfactory tubercle displayed different patterns of
      compartmentalized distribution of zinc. In the dorsal half of the shell of the
      nucleus accumbens, some patches with an intense reaction for zinc seemed to
      overlap with acetylcholinesterase-poor patches. (4) There was a remarkable
      absence of staining for zinc in the globus pallidus. This histochemical study
      illustrates, on the one hand, the high content of vesicular zinc in the dorsal
      and ventral subdivisions of the striatum, which was distributed following
      different patterns of chemical compartmentalization, and on the other hand, the
      absence of vesicular zinc in the globus pallidus of the rat.

PMID- 7644018
TI  - Opposite effects on hippocampal corticosteroid receptors induced by stimulation
      of beta and alpha 1 noradrenergic receptors.
AB  - Central corticosteroid receptors play an important role in the regulation of the
      secretion of corticosterone. Although these receptors are thought to be regulated
      by circulating levels of corticosterone, there is evidence for direct neural
      control. For example, it has been shown that noradrenergic lesions can both
      increase and decrease corticosteroid receptors depending on the brain structure
      involved. In the present study, we investigated the role of different
      noradrenergic receptors in the rat, by examining the effect of the acute
      administration of agonists and antagonists of beta and alpha 1 noradrenergic
      receptors on hippocampal type I and type II corticosteroid receptor levels. The
      effects of these drugs were studied in adrenalectomized animals whose plasma
      levels of corticosterone were maintained in the physiological range by
      implantation of coritcosterone pellets. Our results show that the beta receptor
      agonist salbutamol (5 mg/kg) increased the number of type I and type II
      hippocampal corticosteroid receptors. This effect was blocked by the beta
      receptor antagonist propranolol (5 mg/kg), which had no effect on its own. In
      contrast, the alpha 1 receptor agonist phenylephrine (100 micrograms) reduced the
      number of type I and type II corticosteroid receptors, whereas the alpha 1
      receptor antagonist prazosin (0.5 mg/kg) increased type I receptors. The effect
      of prazosin was attributed to an increase in the relative beta tonus resulting
      from blockade of alpha 1 receptors. Its effect was reversed by the simultaneous
      injection of the beta receptor antagonist propranolol. In conclusion, our results
      show that noradrenergic transmission can have both a facilitatory and an
      inhibitory action on central corticosteroid receptors by acting respectively on
      beta and alpha 1 noradrenergic receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7644019
TI  - Autoradiographic analysis of [35S]t-butylbicyclophosphorothionate binding in
      kindled rat hippocampus shows different changes in CA1 area and fascia dentata.
AB  - We studied the binding of [35S]t-butylbicyclophosphorothionate to the GABAA
      receptor-mediated chloride channel in the CA1 area and fascia dentata of control
      and Schaffer collateral kindled rats, by means of semi-quantitative
      autoradiography. The [35S]t-butylbicyclophosphorothionate binding was determined
      at three stages during kindling acquisition: (i) after six afterdischarges, (ii)
      after 14 afterdischarges and (iii) after the induction of fully kindled seizures.
      Furthermore, the binding was studied at the long-term stage, 28 days after the
      last generalized tonic-clonic seizure [Racine R. J. (1972) Electroenceph. clin.
      Neurophysiol. 32, 281-294]. The binding was investigated at three [35S]t
      butylbicyclophosphorothionate concentrations, 4, 47.5 (KD value) and 180 nM (Bmax
      value). A significant decrease in [35S]t-butylbicyclophosphorothionate binding in
      the CA1 area (-6 to -20%) and hilar formation (-17 to -37%), in one or more of
      the three [35S]t-butylbicyclophosphorothionate concentrations tested at the six
      and 14 afterdischarges and fully kindled stages was observed, but no significant
      changes at the long-term kindling stage were found. In contrast, the granular and
      molecular layers of the fascia dentata presented a significant increase in [35S]t
      butylbicyclophosphorothionate binding (+15 to +38%) at the 14 afterdischarges,
      fully kindled and long-term kindled stages.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7644020
TI  - Ultrastructural analysis of tryptophan hydroxylase immunoreactive nerve terminals
      in the rat cerebral cortex and hippocampus: their associations with local blood
      vessels.
AB  - Physiological evidence has indicated that serotonin (5-hydroxytryptamine) could
      be a regulator of cerebral blood flow in various regions of the brain. In the
      present study, tryptophan hydroxylase immunocytochemistry was used to
      characterize, both at the light and electron microscopic levels, serotonergic
      nerve terminals and primarily their relationships with intraparenchymal
      microarterioles and capillaries in the rat frontoparietal cortex, entorhinal
      cortex and hippocampus. Irrespective of the brain area, serotonergic varicosities
      were primarily apposed to either dendrites or nerve terminals, were on average
      0.37 micron2 in surface area (0.69 micron calculated diameter) and 12-22% of them
      engaged in synaptic junctions, mostly with dendritic elements. Perivascular
      terminals (defined as immunolabelled varicosities located within a 3 micron
      perimeter around the vessel basal lamina) in the frontoparietal cortex
      represented 8-11% of all immunoreactive terminals counted, as determined by light
      and electron microscopy, respectively. In the entorhinal cortex and hippocampus,
      the proportion of perivascular terminals was only determined at the
      ultrastructural level and corresponded to 10% and 4%, respectively. In the
      frontoparietal cortex, serotonergic varicosities were located significantly
      closer (n = 250, 0.98 +/- 0.05 micron; P < 0.001) to the blood vessels than those
      of the entorhinal cortex (n = 116, 1.41 +/- 0.08 microns) or hippocampus (n =
      105, 1.31 +/- 0.08 microns). Of all perivascular serotonergic terminals in the
      frontoparietal cortex, 26% were in the immediate vicinity (0-0.25 micron) of the
      vessel wall, with 2.8% directly abutting on the basement membrane, while 11.6%
      were separated from it only by a thin astrocytic leaflet. This situation
      contrasts with that observed in the entorhinal cortex and hippocampus, where no
      immunoreactive varicosity was ever seen directly contacting the vessel basal
      lamina and with only 10-13% of the terminals being within 0.25 micron from the
      vessels. The surface area of perivascular serotonergic terminals was comparable
      in all regions studied and corresponded to 0.22 micron2; these virtually never
      engaged in synaptic contacts with adjacent neuronal structures. Our results
      indicate that tryptophan hydroxylase-immunolabelled terminals are identical to
      previously characterized serotonin-containing varicosities. Furthermore, the
      present data show intimate associations between serotonergic terminals and
      microvessels in the three regions examined. However, perivascular terminals in
      the frontoparietal cortex were more frequent and/or located much closer to local
      microvessels than those in the other regions, and might be more directly involved
      in neurogenic control of local cerebral blood flow.

PMID- 7644021
TI  - Glucocorticoids, hippocampal corticosteroid receptor gene expression and
      antidepressant treatment: relationship with spatial learning in young and aged
      rats.
AB  - The emergence of cognitive deficits in a subgroup of aged rats is associated with
      increased hypothalamic-pituitary-adrenal axis activity, decreased hippocampal
      mineralocorticoid and/or glucocorticoid receptor gene expression and neuronal
      loss. Short-term treatment with antidepressant drugs in young rats increases
      hippocampal corticosteroid receptor gene expression. In this study, the effects
      of chronic antidepressant administration on hippocampal mineralocorticoid and
      glucocorticoid receptor gene expression and spatial memory in young and aged rats
      were investigated. Young (eight months) and old (22 +/- 1 months) Lister-hooded
      rats were ranked according to watermaze performance. Matched pairs of rats were
      treated with amitriptyline (10 mg/kg) or saline daily for nine weeks, then
      reassessed in the watermaze. Amitriptyline significantly improved spatial memory
      in the young rats (33% increase in transfer test time) and increased hippocampal
      mineralocorticoid, but not glucocorticoid receptor messenger RNA expression. By
      contrast, in aged rats, amitriptyline had no effect on spatial memory or
      hippocampal corticosteroid receptor gene expression, either in cognitively
      unimpaired or cognitively-impaired animals. In aged rats, basal plasma
      corticosterone levels, which were significantly higher than in young animals,
      correlated negatively with spatial memory, while hippocampal glucocorticoid
      receptor mRNA expression correlated negatively with plasma corticosterone levels
      and positively with spatial memory. Amitriptyline had no significant effect on
      basal morning plasma corticosterone levels in either young or aged rats, but
      significantly decreased evening corticosterone levels in aged rats. Our data
      support the notion that corticosterone exerts a concentration-dependent biphasic
      influence, via selective activation of hippocampal mineralocorticoid and
      glucocorticoid receptor, on spatial memory. Amitriptyline improves spatial memory
      in young rats and increases hippocampal mineralocorticoid receptor gene
      expression. The lack of amitriptyline effect on spatial memory in aged rats may
      reflect decreased plasticity of both the synaptic processes underlying spatial
      memory and the regulation of hippocampal mineralocorticoid/glucocorticoid
      receptor expression, with mineralocorticoid receptors fully occupied due to
      elevated basal plasma corticosterone levels (in part a consequence of inadequate
      glucocorticoid receptor function).

PMID- 7644022
TI  - Apolipoprotein E polymorphism influences not only cerebral senile plaque load but
      also Alzheimer-type neurofibrillary tangle formation.
AB  - Only recently, evidence was provided that apolipoprotein E allele epsilon 4
      located on Chromosome 19 is associated with late onset (i.e. senile) sporadic
      Alzheimer's disease. Histologically, Alzheimer's disease is associated with
      intraneuronal neurofibrillary changes and extraneuronal A4/beta-amyloid
      deposition. We set out with a histological staging system which considers the
      gradual development of Alzheimer's disease-related histological changes over time
      and correlates highly with the cognitive decline ante mortem. Our analysis
      revealed that both the mean stage for A4/beta-amyloid deposits and the mean stage
      for neurofibrillary tangles get significantly shifted upwards in epsilon 4
      carriers. This represents an earlier onset of the histopathological process of
      about one decade. The fact that both types of Alzheimer's disease-related changes
      correlate positively with the prevalence of the epsilon 4-allele suggests for a
      causal relationship between the apolipoprotein E polymorphism and the development
      of Alzheimer's disease.

PMID- 7644023
TI  - An inhibitory dopaminergic regulation of the neuropeptide Y immunoreactivity
      expression in the rat cerebral cortex neurons.
AB  - The effect of catecholamine depletion or blockade of dopaminergic or
      noradrenergic receptors on the neuropeptide Y immunoreactivity was studied in the
      rat brain cortex using immunohistochemical methods. Neuropeptide Y immunoreactive
      neurons were counted and the mean density of stained neurons per microscopic
      field was calculated. It was found that monoamine depletion by reserpine, the
      blockade of dopaminergic receptors by haloperidol or the specific D1 receptor
      blockade by SCH23390 caused a significant increase in the neuropeptide Y
      immunoreactivity in the cortex studied, after 24 h, evaluated as the density of
      immunoreactive neurons. No significant changes were observed after the blockade
      of alpha or beta adrenergic receptors (by phenoxybenzamine or propranolol,
      respectively). Specific D2 receptor blockade by sulpiride induced an
      insignificant increase only. The results suggest the existence of an inhibitory
      dopaminergic control of the neuropeptide Y content, mainly via D1 receptors, in
      neurons of the rat brain cortex.

PMID- 7644024
TI  - Involvement of P-type calcium channels in high potassium-elicited release of
      neurotransmitters from rat brain slices.
AB  - Several types of voltage-dependent calcium channels appear to occur in neurons,
      although coupling of the particular subtype of calcium channels to the release of
      neurotransmitter has not been clearly understood. We have examined the effects of
      subtype-specific inhibitors of the calcium channels on depolarization-induced
      release of endogenous neurotransmitters from brain slices. High potassium-induced
      release of glutamate and aspartate from hippocampal and striatal slices was
      almost completely inhibited by a P-type channel blocker, omega-agatoxin IVA.
      omega-Agatoxin IVA also completely inhibited the release of serotonin from the
      hippocampal slices with almost the same potency as in the case of glutamate,
      whereas the potency in blocking the release of serotonin and dopamine from
      striatal slices was lower than that from the hippocampal slices. Another calcium
      channel blocker, omega-agatoxin TK, that was recently found to block P-type
      channels with very similar selectivity and potency to omega-agatoxin IVA, also
      inhibited the release of amino acid transmitters and monoamines, though its
      potency was lower than that of omega-agatoxin IVA. An N-type channel blocker,
      omega-conotoxin GVIA, partially inhibited the neurotransmitter release, but an L
      type channel blocker, nifedipine was ineffective. We propose that the activation
      of P-type calcium channels makes a major contribution to depolarization-elicited
      neurotransmitter release in the CNS and that multiple P-type channels sensitive
      to omega-agatoxin IVA and omega-agatoxin TK modulate the neurotransmitter
      release.

PMID- 7644025
TI  - Changes in brain somatostatin in memory-deficient rats: comparison with
      cholinergic markers.
AB  - To clarify the functional role of the brain somatostatinergic system in cognitive
      processes, changes in the performance in passive avoidance and water maze tasks
      and in brain somatostatin contents were comparatively investigated in young
      Fischer rats subjected to brain cholinergic and somatostatinergic depletion, and
      in aged Fischer rats. Lesioning of the nucleus basalis magnocellularis and
      administration of cysteamine (200 mg/kg, s.c.), a depletor of somatostatin,
      resulted in significant deficits in passive avoidance, but complete transection
      of the fimbria-fornix hardly affected the performance in the task. When cognitive
      performance was assessed in the Morris water maze, lesions of the nucleus basalis
      magnocellularis and the fimbria-fornix, and administration of cysteamine,
      significantly impaired the acquisition of navigatory spatial memories of rats. On
      the other hand, aged rats (24-27 months) showed severe impairments of memory
      acquisition in both tasks. Neurochemistry measurements showed that lesions of the
      nucleus basalis magnocellularis produced a selective reduction both in the
      cortical cholinergic marker choline acetyltransferase and in striatal
      somatostatin level, whereas lesioning of the fimbria-fornix caused a marked loss
      of choline acetyltransferase in the hippocampus and posterior cortex, and a
      significant reduction in hippocampal somatostatin. On the other hand, treatment
      with cysteamine significantly reduced the contents of somatostatin in all the
      brain regions examined, but minimally affected choline acetyltransferase
      activity. However, significant reduction in the striatal choline
      acetyltransferase activity and elevation in somatostatin content in the frontal
      cortex were found in aged rats compared with young rats. Taken together, these
      results strongly suggest that changes in the brain somatostatinergic transmission
      are involved in the cognitive deficits in the experimental animal models of
      dementia presently employed. Furthermore, the present comparative study further
      implies that there are differences in the relative involvement of the cholinergic
      and somatostatinergic systems in the performance of rats on two different tests
      of mnemonic function.

PMID- 7644026
TI  - Autoradiographic and electrophysiological evidence for the existence of
      neurotensin receptors on cultured astrocytes.
AB  - By means of autoradiography we have studied the cellular localization of binding
      sites for [3H]neurotensin and its nonpeptide receptor antagonist [3H]SR-48692 in
      explant cultures of rat neocortex, striatum, brain stem and spinal cord. Binding
      sites for the peptide and its antagonist were observed on a great number of
      astrocytes in all CNS regions studied. Simultaneous staining of the cultures with
      a monoclonal antibody against glial fibrillary acidic protein has shown that the
      labelled cells in the outgrowth zone of the cultures were glial fibrillary acidic
      protein-positive and could therefore be identified as astrocytes. In addition to
      astrocytes, many neurons and outgrowing nerve fibres were labelled by the
      radioligands. Binding of [3H]neurotensin and [3H]SR-48692 (10(-8)M) to neurons
      and glial cells was markedly reduced or inhibited by the unlabelled compounds at
      high concentration (10(-6)M), suggesting "specific" binding of the radioligands.
      Electrophysiological studies have shown that addition of neurotensin to the
      bathing solution caused a hyperpolarization of the majority of astrocytes tested.
      There was a dose-response relationship between the magnitude of the
      hyperpolarization and the concentration of the peptide (10(-10)-10(-7)M); 10(
      10)M being the threshold concentration. The specificity of the action of
      neurotensin was confirmed by the selective nonpeptide neurotensin receptor
      antagonist SR-48692 which reversibly blocked or markedly reduced the
      hyperpolarization by the peptide on all astrocytes tested. Our
      electrophysiological findings together with our autoradiographic data provide
      strong evidence for the presence of specific and functional neurotensin receptors
      on astrocytes.

PMID- 7644027
TI  - Extracellular concentration of endogenous free D-serine in the rat brain as
      revealed by in vivo microdialysis.
AB  - Using an in vivo microdialysis technique, we have measured the extracellular
      concentration of endogenous free D-serine in comparison with that of L-serine,
      glycine and L-glutamate in the discrete brain areas of the freely moving rat. A
      high concentration of D-serine was observed in the dialysate obtained from the
      medial prefrontal cortex and striatum, whereas the cerebellar dialysate contained
      only a trace amount of the D-amino acid. The regional variation in the basal
      overflow of D-serine was proportional to that of its tissue levels which has been
      shown to closely correlate with the distribution of the N-methyl-D-aspartate type
      excitatory amino acid receptor. In contrast, the extracellular release of glycine
      and L-glutamate was higher in the cerebellum and very low in the striatum. The
      extracellular concentrations of L-serine were more than three times those of
      striatal D-serine in the three regions. Neither addition of a sodium channel
      blocker, tetrodotoxin (2 microM), nor deprivation of Ca2+ from the perfusate
      reduced the basal extracellular levels of the four amino acids tested in the
      medial prefrontal cortex. Furthermore, intra-frontal cortex perfusion of a sodium
      channel activator, veratrine (200 micrograms/ml), caused an increase in the
      extracellular release of glycine and L-glutamate but a slight decrease in that of
      D-serine in a tetrodotoxin-sensitive manner in the cortical region.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7644028
TI  - Distribution of protein kinase C (alpha, beta, gamma subtypes) in normal nerve
      fibers and in regenerating growth cones of the rat peripheral nervous system.
AB  - The distribution of protein kinase C (alpha, beta, gamma subtypes) was studied
      using immunocytochemical techniques in normal nerve fibers and in regenerating
      sprouts (growth cones) from the nodes of Ranvier following crush injuries to the
      rat peripheral nervous system. In normal nerves, for each protein kinase C
      subtype, immunoreactivity was present in both myelinated and unmyelinated axons.
      In myelinated axons, immunoreactivity for all three subtypes was patchy in the
      axoplasm and diffuse in the subaxolemmal peripheral zones. No immunoreactivity
      was found in the microtubule and neurofilament (cytoskeletal) domain. In
      contrast, in unmyelinated axons, immunoreactivity was distributed diffusely in
      the axoplasm. Schwann cells of myelinated fibers exhibited protein kinase C
      immunoreactivity, but those of unmyelinated fibers did not. In regenerating
      nerves, early sprouts and growth cones extending through the crushed site along
      Schwann cell basal laminae exhibited intense immunoreactivity for all three
      subtypes. Immunoreactivity was distributed diffusely throughout the axoplasm of
      the regenerating sprouts (growth cones), in which microtubules and neurofilaments
      were very rare. Thus, the subcellular localization of the protein kinase C
      immunoreactivity in growth cones of early regenerating nerves differed from that
      of normal parent axons. These findings suggest that protein kinase C (alpha, beta
      and gamma subtypes), whose subcellular distribution becomes more extensive in
      regenerating axons, may have important functional roles in axonal sprouting and
      in the regulation of growth cone activity in the peripheral nervous system.

PMID- 7644030
TI  - NK1-tachykinin receptors and prolonged, stimulus-evoked alterations in the
      excitability of withdrawal reflexes in the decerebrated and spinalized rabbit.
AB  - Intense natural or electrical stimulation of afferents from the toes or the heel
      results in prolonged changes in the excitability of the heel withdrawal reflex
      pathway in the rabbit. This study has investigated the roles played by tachykinin
      NK1 receptors in mediating these effects. Reflexes were evoked by electrical
      stimulation of the sural nerve and recorded from the gastrocnemius medialis
      muscle nerve. High-intensity electrical stimulation of the common peroneal nerve,
      or application of a crush stimulus to the toes, resulted in suppression of
      gastrocnemius reflex responses to between 30 and 50% of controls, from which
      recovery was complete in 15-25 min. In contrast, intense electrical stimulation
      of the sural nerve, or application of mustard oil to the heel, facilitated the
      sural to gastrocnemius reflex to two to four times control values. Recovery was
      rarely complete within 30 min of these stimuli. Administration of the NK1
      receptor antagonist CP-96,345, but not its enantiomer CP-96,344, reduced
      gastrocnemius reflex responses to sural nerve stimulation per se; significantly
      decreased the time to recovery after common peroneal nerve stimulation and toe
      crush (but did not affect maximum inhibition); and significantly reduced the
      facilitation of reflexes resulting from sural nerve stimulation or mustard oil
      applied to the heel in the first 3-5 min after the application of the stimuli.
      Both CP-96,345 and CP-96,344 reduced blood pressure and heart rate. These data
      show that: (i) blockade of NK1-receptors reduces excitatory drive from sural
      nerve afferents to GM motoneurones; (ii) NK1-receptors are involved in the
      generation of the early excitatory events which follow stimulation of nociceptive
      afferents from the heel; and (iii) have a role in the later stages of prolonged,
      opioid-mediated inhibition of reflexes resulting from activation of fine
      afferents from the toes. We believe that (ii) and (iii) reflect a role for
      tachykinins as transmitters from small diameter primary afferent fibres.

PMID- 7644029
TI  - Visualization and immunohistochemical characterization of sympathetic and
      parasympathetic neurons in the male rat major pelvic ganglion.
AB  - Pelvic ganglia contain a mixture of sympathetic and parasympathetic neurons which
      are innervated by either lumbar (sympathetic) or sacral (parasympathetic)
      preganglionic axons, respectively. However, until recently no stain for these
      axon terminals has been available. In the present study of the male rat major
      pelvic ganglion, a ganglion which supplies axons to the lower urinary and
      digestive tracts and internal reproductive organs, the total population of
      preganglionic axon terminals was immunostained using an antiserum against
      synaptophysin, a protein associated with all small synaptic vesicles (such as the
      presumptive cholinergic vesicles present in all preganglionic terminals).
      Selective bilateral lesions of either the hypogastric or pelvic nerves, which
      carry the sympathetic and parasympathetic preganglionic axons, respectively, were
      carried out and three to seven days later ganglia were examined
      immunohistochemically for the distribution of residual synaptophysin-positive
      terminals. Neurons remaining innervated following hypogastric nerve lesion were
      therefore classified as parasympathetic and those innervated after pelvic nerve
      section were defined as sympathetic. These two cell groups are present in
      approximately equal proportions. Double-staining immunofluorescence to identify
      which transmitters or peptides are present in either sympathetic or
      parasympathetic neurons showed that the majority (approximately 75%) of
      sympathetic neurons are presumed to be noradrenergic (i.e. contain tyrosine
      hydroxylase immunoreactivity) and are also immunoreactive for neuropeptide Y; the
      remainder contain vasoactive intestinal peptide-immunoreactivity but not tyrosine
      hydroxylase and may be cholinergic. Parasympathetic neurons were virtually all
      non-noradrenergic (tyrosine hydroxylase negative) and were also of two
      histochemical types, with some neurons containing neuropeptide Y- and others
      containing vasoactive intestinal peptide-immunoreactivity.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7644031
TI  - GABAA receptor-like immunoreactivity in the goldfish brainstem with emphasis on
      the Mauthner cell.
AB  - The distribution of the GABAA receptor in the goldfish brainstem and on the
      Mauthner cell membrane was investigated with both optical and electron microscopy
      using a polyclonal antibody raised against the intracellular loop of the rat
      gamma 2 subunit. At the optical level, immunofluorescent dots were detected on
      small and large neurons belonging to vestibular and reticular nuclei. On the
      Mauthner cell plasmalemma, a gamma 2-like immunoreactivity was observed
      predominantly on the tip of the lateral dendrite. Fluorescent parches were
      intermingled with a more diffuse staining. Immunoreactive spots of weaker
      intensity were also present on the soma and some were also observed inside and
      within the periphery of the axon-cap as well. Observations at the electron
      microscopic level revealed that the peroxidase end-product predominates
      postsynaptically in front of release sites in the studied nuclei and on the
      Mauthner cell. On the lateral dendrite of the neuron, numerous immunopositive
      postsynaptic differentiations were encountered on spines. Stained glial elements
      were encountered in the different areas studied. These results demonstrate that
      the GABAA receptor gamma 2 subunit has a precise distribution on neuronal
      membranes and suggest that it could be involved in the remote dendritic
      inhibition of the Mauthner cell and in the control of input-output properties of
      both vestibular and reticular nuclei.

PMID- 7644033
TI  - Mating and agonistic behavior produce different patterns of Fos immunolabeling in
      the male Syrian hamster brain.
AB  - Previous work has shown that mating induces the expression of Fos protein within
      the chemosensory pathways of the male Syrian hamster brain. However, it is not
      known if this pattern of labeling is specific to mating or the result of social
      interactions in general. To determine the behavioral specificity of activation
      within these pathways, Fos immunostaining following mating was compared to that
      following agonistic behavior. Both mating and agonistic behavior are dependent
      upon chemosensory cues and gonadal steroids (reviewed in Refs 64, 65) and areas
      belonging to the olfactory and vomeronasal pathways process chemosensory and
      hormonal information (reviewed in Ref. 48). The results of this study demonstrate
      both similarities and differences in brain activation patterns following these
      two social behaviors. Agonistic behavior increased the number of Fos
      immunoreactive neurons within most subdivisions of the medial amygdala, the
      anteromedial and posterointermediate bed nucleus of the stria terminalis, the
      ventrolateral septum and the ventral premammillary nucleus of the hypothalamus in
      a pattern comparable to that observed after mating. This pattern of activation
      common to mating and agonistic behavior may reflect an increase in an animal's
      general state of arousal during social interactions. In contrast, although mating
      and agonistic behavior both activated neurons within the caudal subdivision of
      the medial nucleus of the amygdala, the anterodorsal level of posteromedial bed
      nucleus of the stria terminalis and the paraventricular and ventromedial nuclei
      of the hypothalamus, in these areas either the distribution and/or number of Fos
      immunoreactive neurons differed. In addition, agonistic behavior selectively
      activated neurons within the anterolateral bed nucleus of the stria terminalis,
      the anterior nucleus of the hypothalamus and the dorsal periaqueductal gray,
      whereas mating alone activated neurons within the posteroventral level of
      posteromedial bed nucleus of the stria terminalis and the medial preoptic area.
      No differences were found between dominant and subordinate males following
      agonistic behavior. These observations along with results from other laboratories
      suggest that mating and agonistic behavior activate distinct neural circuits.

PMID- 7644032
TI  - The expression and distribution of tau proteins and messenger RNA in rat dorsal
      root ganglion neurons during development and regeneration.
AB  - Microtubule-associated proteins contribute to the balance between stability and
      plasticity of the neuronal cytoskeleton by modulating assembly and disassembly of
      microtubules. The tau microtubule-associated proteins exist in several isoforms
      which are developmentally regulated and differentially distributed. Our objective
      was to characterize the distribution of tau isoforms in developing and mature
      dorsal root ganglia neurons and during axonal regeneration following sciatic
      nerve axotomy. Immunocytochemical analysis was carried out using antibodies that
      recognize all tau isoforms and a novel antibody that specifically recognizes the
      high molecular weight isoform. The expression of tau is highly regulated during
      development. At E14, all dorsal root ganglion neurons express only the low
      molecular weight tau isoforms. These isoforms are still present in all dorsal
      root ganglion neurons in neonates, whereas high molecular weight tau isoforms are
      expressed in a subset of dorsal root ganglion neurons. The switch from low to
      exclusively high molecular weight tau expression begins at E18 and is completed
      during the first postnatal week. In the adult, high molecular weight tau is
      restricted to small- and medium-sized dorsal root ganglion neurons; its
      distribution largely coincides with the population of substance P and calcitonin
      gene related peptide peptidergic neurons. This differential distribution was
      observed in the cell body, dorsal roots and sciatic nerve axons. In contrast to
      the protein, however, the distribution of high molecular weight tau messenger RNA
      is not restricted; all dorsal root ganglion neurons express similar tau messenger
      RNA levels. The discrepancy between the distribution of protein and messenger RNA
      suggests control at the post-transcriptional or translational levels. Sciatic
      nerve axotomy which is followed by axonal regeneration did not alter the
      differential distribution of high molecular weight tau immunostaining. We
      conclude that the distribution and expression of tau isoforms during axonal
      regeneration in adult does not recapitulate the developmental pattern.

PMID- 7644034
TI  - Delivery of a foreign gene to sympathetic preganglionic neurons using recombinant
      herpes simplex virus.
AB  - Two recombinant herpes simplex type 1 viruses expressing beta-galactosidase
      (encoded by the Escherichia coli lacZ gene) inserted into the unique long 41
      (encoding virus host shutoff) or unique short 5 (encoding glycoprotein J) open
      reading frames were generated. Purified recombinants or wild-type herpes simplex
      type 1 were injected into the left adrenal gland of hamsters. Three days later,
      virus-infected neurons were detected in spinal cord sections from all infected
      hamsters. Neurons were visualized with beta-galactosidase histochemistry in
      spinal cord sections from hamsters infected with either of the recombinants but
      not with the wild-type virus. Wild-type virus could only be detected with
      immunocytochemistry. Insertional mutagenesis into the unique long 41 or unique
      short 5 regions of the herpes simplex genome by lacZ did not disrupt the
      neurotropic properties of the virus. Both recombinant viruses labelled the
      central nervous system sympathoadrenal preganglionic neurons as well as brainstem
      neurons. Because the virus host shutoff recombinant more readily crossed synapses
      to reach the brainstem compared to the glycoprotein J recombinant, the presence
      of glycoprotein J may facilitate cell to cell transmission in vivo. Both
      recombinants may be useful for the study of synaptic organization of neural
      circuits. Our recombinant viruses were less lytic yet neurovirulent after
      mutation of either glycoprotein J or virus host shutoff of herpes simplex virus
      type 1 wild-type. These recombinant viruses express the bacterial beta
      galactosidase which is readily detectable using simple histochemistry.
      Inoculation of the adrenal gland or kidney with these viruses led to clear
      labelling of spinal cord cells. These viruses may be useful markers of specific
      neural circuits.

PMID- 7644035
TI  - Octopamine and Leydig cell stimulation depress the afterhyperpolarization in
      touch sensory neurons of the leech.
AB  - In touch sensory neurons of the leech, a train of spikes evoked by intracellular
      electrical stimulation leads to an afterhyperpolarization, mainly due to the
      activation of the Na+/K+ electrogenic pump and partly to a Ca(2+)-activated K+
      conductance. It has been found that serotonin is able to reduce the
      afterhyperpolarization through the inhibition of the Na+/K+ electrogenic pump. We
      have investigated the possible modulation of the afterhyperpolarization by other
      endogenous neurotransmitters and we have found that octopamine is also able to
      reduce its amplitude. The electrical stimulation of the octopaminergic Leydig
      neurons mimics this effect. We have compared the actions of the two amines and
      found that the effect of serotonin is blocked by methysergide but not by high
      [Mg2+] or by phentolamine, and it is still present in touch cells isolated in
      culture. On the contrary, the octopamine modulation of the afterhyperpolarization
      does not occur in single touch cells in culture and it is blocked by all these
      treatments. These data suggest that while serotonin should act monosynaptically,
      octopamine should act through a serotonergic pathway.

PMID- 7644036
TI  - Current concepts in the diagnosis of cobalamin deficiency.

PMID- 7644037
TI  - Do nonsteroidal anti-inflammatory drugs decrease the risk for Alzheimer's
      disease? The Rotterdam Study.
AB  - Based on reports that the use of nonsteroidal anti-inflammatory drugs (NSAIDs)
      may reduce the risk for Alzheimer's disease (AD), we studied the cross-sectional
      relation between NSAID use and the risk for AD in a population-based study of
      disease and disability in older people. After controlling for age, education,
      gender, and use of benzodiazepines, we found a relative risk (RR) for AD of 0.38
      (0.15 to 0.95) when comparing NSAID users (n = 365) to NSAID non-users (n =
      5,893). To address confounding by indication or contraindication, we compared
      NSAID users with a subset of NSAID non-users who were using topical medication
      for ear, eye, or dermatologic conditions (n = 365). In this comparison, the
      adjusted RR for AD was 0.54 (0.16 to 1.78). These findings are compatible with a
      possible protective effect of NSAIDs on the risk for AD.

PMID- 7644039
TI  - The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part XI.
      Clinical milestones in patients with Alzheimer's disease followed over 3 years.
AB  - The rate of cognitive decline, measured by psychometric testing, is widely used
      to track the progression of Alzheimer's disease (AD). As an alternative approach,
      we studied clinical measures as markers of the progression of dementia in 343
      community-dwelling patients with probable AD enrolled in the multi-center
      Consortium to Establish a Registry for Alzheimer's Disease (CERAD) project.
      Subjects received standardized evaluations at entry and at annual follow-up.
      Decline on the Clinical Dementia Rating, loss of instrumental activities of daily
      living, failure to recall three words on the Mini-Mental State Examination
      (MMSE), and decline of the total MMSE score to below 10 were high-risk
      milestones, with cumulative frequencies exceeding 50% at 3 years. Loss of
      dressing and toileting activities occurred at intermediate rates, while loss of
      eating ability was rare. The risk of reaching clinical milestones and the annual
      rate of cognitive decline on the MMSE were directly correlated. Clinical
      milestones are useful indices of the progression of dementia in patients with AD.

PMID- 7644038
TI  - Intelligence and education as predictors of cognitive state in late life: a 50
      year follow-up.
AB  - We evaluated the relation of education and intelligence in early adult life to
      cognitive function in a group of elderly male twins. The Army General
      Classification Test (AGCT) was administered to US armed forces inductees in the
      early 1940s. Fifty years later, as part of a study of dementia in twins, we
      tested the cognitive status of 930 of these men using the modified Telephone
      Interview for Cognitive Status (TICS-m). TICS-m scores obtained in later life
      were correlated with AGCT scores (r = 0.457) and with years of education (r =
      0.408). Thus, in univariate analyses, the AGCT score accounted for 20.6% and
      education accounted for 16.7% of variance in cognitive status. However, these two
      effects were not fully independent. A multivariable model using AGCT score,
      education, and the interaction of the two variables as predictors of the TICS-m
      score explained 24.8% of the variance, a slightly but significantly greater
      proportion than was explained by either factor alone. In a separate analysis
      based on 604 pairs of twins who took the AGCT, heritability of intelligence
      (estimated by AGCT score) was 0.503. Although this study does not address the
      issue of education and premorbid IQ as risk factors for dementia, the findings
      suggest that basic cognitive abilities in late life are related to cognitive
      performance measures from early adult life (ie, education and IQ).

PMID- 7644040
TI  - CT and MRI findings among African-Americans with Alzheimer's disease, vascular
      dementia, and stroke without dementia.
AB  - We compared CT and MRI findings among 78 Alzheimer's disease (AD), 66 vascular
      dementia (VaD), and 41 stroke without dementia (SWD) African-American patients to
      identify possible neuroimaging indicators of dementia. The patients with AD and
      VaD were generally older and less educated than those with SWD. VaD and SWD
      patients had a higher frequency of cardiovascular disease risk factors than those
      with AD. In multivariate analysis, the CT data showed that the presence of white
      matter lesions, nonlacunar infarcts, and left subcortical infarcts were
      predictors of VaD when compared with AD, whereas atrophy of the third ventricle
      and equal distribution of white matter lesions distinguished VaD from SWD. On
      MRI, atrophy of the temporal sulci, temporal horns, and the third ventricle, and
      right hemisphere infarcts, distinguished AD from VaD, while atrophy of the third
      ventricle differentiated VaD from SWD. These data suggest that atrophy,
      especially at the level of the third ventricle, presence of infarcts, and white
      matter lesions may be useful predictors of dementia subtype. Furthermore, the
      qualitative CT and MRI findings among our African-American patients were similar
      to those reported in other dementia studies.

PMID- 7644041
TI  - Serial magnetic resonance imaging in isolated angiitis of the central nervous
      system.
AB  - Isolated angiitis of the central nervous system (IACNS) is a rare form of
      vasculitis restricted to the CNS. We report serial MRI findings in a biopsy
      proven case of IACNS. MRI showed extensive white matter and subcortical disease.
      Before specific treatment, neuroimaging showed the development of new lesions
      corresponding with an overall progressive clinical course of the illness; the
      post-treatment MRI showed improvement.

PMID- 7644042
TI  - Transient trochlear nerve palsy following anterior temporal lobectomy for
      epilepsy.
AB  - Three of 22 patients (14%) who underwent anterior temporal lobectomy for
      treatment of medically intractable epilepsy at our institution from July 1987
      through July 1993 experienced diplopia immediately after surgery. We found
      ipsilateral paresis of the superior oblique muscle in all three patients. Their
      ophthalmoplegia resolved completely within 14 weeks. We did not observe any new
      structural or ischemic changes on postoperative MRIs to account for their
      deficits. Trochlear nerve palsy--not oculomotor nerve palsy, as is reported in
      most reference texts--is a relatively common cause of transient diplopia
      following temporal lobectomy. Indirect (ie, traction) injury of the trochlear
      nerve is a plausible mechanism that would explain this complication.

PMID- 7644043
TI  - Idiopathic generalized epilepsy of adolescence: are the syndromes clinically
      distinct?
AB  - Juvenile myoclonic epilepsy, juvenile absence epilepsy, and epilepsy with
      generalized tonic-clonic seizures (GTCS) on awakening are the three syndromes of
      idiopathic generalized epilepsy of adolescent onset currently included in the
      classification of epilepsy syndromes of the International League Against Epilepsy
      (ILAE). Although they differ in their predominant seizure types, the syndromes
      share several clinical features, thus giving rise to questions of phenotypic
      overlap and purity. We studied the clinical features of 101 patients with
      idiopathic generalized epilepsy beginning in adolescence. A standardized
      interview was used to elucidate seizure phenomenology, precipitants, frequency,
      and response to treatment. Groups defined by seizure type were compared and their
      similarities examined. The group with myoclonic but not absence seizures (21
      patients) corresponded to the ILAE syndrome of juvenile myoclonic epilepsy,
      whereas those with absences but not myoclonus (37 patients) resembled juvenile
      absence epilepsy. Twenty-six patients shared the features of juvenile myoclonic
      epilepsy and juvenile absence epilepsy. Epilepsy with GTCS on awakening was not a
      specific syndromic entity; 10 patients had this seizure type alone. Seven
      patients were without a syndromic diagnosis. In these patients only GTCS
      occurred, but neither on awakening nor in the evening period of relaxation. We
      conclude that whilst syndromes of idiopathic generalized epilepsy of adolescence
      can be recognized, the current classification does not include all patients. In
      addition, the boundaries between the syndromes are indistinct, suggesting
      underlying neurobiological, possibly genetic, relationships.

PMID- 7644044
TI  - The neuropsychological pattern of corticobasal degeneration: comparison with
      progressive supranuclear palsy and Alzheimer's disease.
AB  - The pattern of cortical and subcortical neuropathologic lesions in corticobasal
      degeneration (CBD) should predict a specific cognitive profile in this disease.
      To characterize this profile and to determine its specificity by comparison with
      progressive supranuclear palsy (PSP) and senile dementia of the Alzheimer's type
      (SDAT), we used an extensive neuropsychological battery assessing global
      efficiency, executive functions, various tests of encoding and retrieval, dynamic
      motor organization, and upper limb praxis. We compared the performance of
      patients with CBD (n = 15) with that of controls (n = 19) matched for age and
      education, and with that of patients with PSP and SDAT (15 in each group),
      matched for severity of dementia and depression. Patients with CBD showed: (1) a
      moderate global deterioration; (2) a dysexecutive syndrome similar to that of
      patients with PSP and more severe than in SDAT; (3) explicit learning deficits,
      without retention difficulties and easily compensated by using the same semantic
      cues at encoding and retrieval as in PSP; this was in contrast with SDAT where
      cued recall and recognition were also impaired; (4) disorders of dynamic motor
      execution (temporal organization, bimanual coordination, control, and inhibition)
      similar to those of patients with PSP and not in SDAT; (5) asymmetric praxis
      disorders (posture imitation, symbolic gesture execution, and object utilization)
      that were not observed in PSP or SDAT. Patients with CBD show a specific
      neuropsychological pattern associating a dysexecutive syndrome, likely due to
      degeneration of the basal ganglia and prefrontal cortex, and asymmetric praxis
      disorders, which might be related to premotor and parietal lobe lesions. This
      neuropsychological profile may help to distinguish this condition clinically from
      other neurodegenerative diseases.

PMID- 7644045
TI  - Risk factors for lacunar infarction syndromes.
AB  - BACKGROUND AND PURPOSE: Lacunar infarction is an important stroke subgroup with
      unique clinical and pathologic features, but its relative risks for associated
      risk factors have been rarely documented. To address this matter, we studied 203
      consecutive patients with first-ever stroke due to lacunar infarction admitted to
      four general hospitals during the period 1985 to 1992. METHODS: We obtained
      information concerning risk factor exposure status among the patients by
      interview using a structured questionnaire and by comparison with age- and sex
      matched neighborhood controls. Odds ratios were estimated with adjustment for
      confounding variables by using multivariate logistic regression. RESULTS:
      Significantly increasing the risk of lacunar stroke were hypertension (with an
      odds ratio of 8.9 [95% confidence intervals 4.2, 18.8]), current smoking (6.6
      [2.9, 14.8]), and diabetes (2.3 [1.0, 5.5]), whereas frequent physical exercise
      was associated with a significantly decreased risk (0.3 [0.1, 0.7]). There was no
      risk of lacunar stroke associated with heart disease (odds ratio 1.0 [0.5, 1.9]).
      CONCLUSIONS: Patients with hypertension or diabetes, and those who currently
      smoke, are at a higher risk of lacunar stroke, whereas those who undertake
      regular physical exercise may be at lower risk. The high risk associated with
      hypertension but absent risk with heart disease supports the "lacunar hypothesis"
      of a unique pathophysiologic mechanism for lacunar stroke.

PMID- 7644046
TI  - The Warfarin-Aspirin Symptomatic Intracranial Disease Study.
AB  - We conducted a retrospective, multicenter study to compare the efficacy of
      warfarin with aspirin for the prevention of major vascular events (ischemic
      stroke, myocardial infarction, or sudden death) in patients with symptomatic
      stenosis of a major intracranial artery. Patients with 50 to 99% stenosis of an
      intracranial artery (carotid; anterior, middle, or posterior cerebral; vertebral;
      or basilar) were identified by reviewing the results of consecutive angiograms
      performed at participating centers between 1985 and 1991. Only patients with TIA
      or stroke in the territory of the stenotic artery qualified for inclusion in the
      study. Patients were prescribed warfarin or aspirin according to local physician
      preference and were followed by chart review and personal or telephone interview.
      Seven centers enrolled 151 patients; 88 were treated with warfarin and 63 were
      treated with aspirin. Median follow-up was 14.7 months (warfarin group) and 19.3
      months (aspirin group). Vascular risk factors and mean percent stenosis of the
      symptomatic artery were similar in the two groups, yet the rates of major
      vascular events were 18.1 per 100 patient-years of follow-up in the aspirin group
      (stroke rate, 10.4/100 patient-years; myocardial infarction or sudden death rate,
      7.7/100 patient-years) compared with 8.4 per 100 patient-years of follow-up in
      the warfarin group (stroke rate, 3.6/100 patient-years; myocardial infarction or
      sudden death rate, 4.8/100 patient-years). Kaplan-Meier analysis showed a
      significantly higher percentage of patients free of major vascular events among
      patients treated with warfarin (p = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7644047
TI  - Comparative cognitive effects of phenobarbital, phenytoin, and valproate in
      healthy adults.
AB  - The relative effects of antiepileptic drugs (AEDs) on cognition are
      controversial. We compared the cognitive effects of phenobarbital, phenytoin, and
      valproate in 59 healthy adults using a randomized, double-blind, incomplete
      block, crossover design. Cognitive assessments were conducted at baseline, after
      1 month on each drug (two AEDs per subject), and at two repeat baselines 11 weeks
      after each AED treatment. The neuropsychological battery included 12 tests,
      yielding 22 variables: Choice Reaction Time, P3 Event-Related Potential, Finger
      Tapping, Lafayette Grooved Pegboard, Selective Reminding Test, Paragraph Memory,
      Complex Figures, Symbol Digit Modalities Test, Stroop Test, Visual Serial
      Addition Test, Hopkins Symptom Checklist, and Profile of Mood States. More than
      one-half of the variables exhibited AED effects when compared with nondrug
      baselines, and all three AEDs produced some untoward effects. Differential AED
      effects on cognition were present for approximately one-third of the variables.
      Phenobarbital produced the worst performance; there was no clinically significant
      difference between phenytoin and valproate.

PMID- 7644048
TI  - Complex partial status epilepticus accompanied by serious morbidity and
      mortality.
AB  - Nonconvulsive status epilepticus (NCSE) accounts for approximately 20% of all
      status epilepticus (SE). Although convulsive SE is recognized as a medical
      emergency, prompt diagnosis and treatment of patients with NCSE is often not
      emphasized because its consequences are thought to be benign. We report 10
      patients with persistent neurologic deficits or death after well-documented NCSE
      in the form of complex partial status epilepticus (CPSE). All patients had
      prolonged CPSE lasting 36 hours or longer, as documented by clinical and EEG
      findings. Causes for CPSE were preexisting epilepsy with partial and secondarily
      generalized seizures (3 patients), vascular disease (2 patients), encephalitis (2
      patients), and metabolic disease (1 patient); causes were unknown for two
      patients. Poor outcomes identified included persistent (lasting at least 3
      months) or permanent cognitive or memory loss (5 patients), cognitive or memory
      loss plus motor and sensory dysfunction (3 patients), and death (3 patients).
      NCSE in the form of CPSE is not a benign entity. Serious morbidity and mortality
      may occur due to the adverse effects of prolonged seizures and as a result of
      acute brain disorders that precipitate the seizures.

PMID- 7644049
TI  - Oral sumatriptan in preventing headache recurrence after treatment of migraine
      attacks with subcutaneous sumatriptan.
AB  - Headache recurrence (HR) may occur within 24 hours in approximately 40% of
      migraine attacks initially treated successfully with 6 mg subcutaneous (SC)
      sumatriptan. This may be due to the short plasma half-life of sumatriptan. We
      studied whether an additional dose of 100 mg oral sumatriptan 4 hours after
      treatment of a migraine attack with 6 mg SC sumatriptan could prevent HR.
      Patients (n = 667) treated up to three migraine attacks in a randomized, double
      blind, placebo-controlled, parallel-group, multicenter clinical trial. For each
      attack, they initially took open-label 6 mg SC sumatriptan by autoinjector. Four
      hours later all patients took either 100 mg oral sumatriptan or matched placebo.
      Patients could take an additional optional oral dose of 100 mg sumatriptan to
      treat HR. The primary efficacy end point was the number of successfully treated
      patients without HR within 24 hours after the initial SC injection for the first
      study attack. Two hundred twenty-five patients were not assessable for HR, mainly
      because of protocol violations. Of 442 assessable patients, 82/212 in the
      sumatriptan-treated group (39%) and 89/230 in the placebo-treated group (39%)
      reported HR in attack 1. Median times to recurrence were 15.6 hours after
      sumatriptan and 10.3 hours after placebo (p = 0.006). One hundred mg oral
      sumatriptan taken 4 hours after 6 mg SC sumatriptan does not prevent HR but
      significantly delays time to recurrence.

PMID- 7644050
TI  - Study of the afferent pathways from the rectum with a new distention control
      device.
AB  - Quantitative studies of the afferent pathways from hollow viscera have been
      limited by the lack of an easily controlled, reproducible visceral stimulus. We
      adapted a slow distention device to allow for rapid distention to study the
      afferent pathways from the rectum. The device produced a pressure increase of 10
      mm Hg in 42 msec and of 20 mm Hg in 60 msec. We recorded cerebral evoked
      potentials (EPs) after rectal balloon distention in 17 healthy subjects. Several
      averages of 25 to 50 rectal distentions at 0.17-Hz frequency were recorded. The
      responses consisted of multiple peaks within 200 msec after stimulation. The mean
      latency of the initial positive peak was 44 msec, suggesting that a myelinated
      pathway was stimulated with mechanical rectal distention. Our device produced
      reliable and repeatable EPs that were independent of balloon characteristics or
      rectal pressures. EP recording after rectal stimulation may become a useful
      technique for the physiologic investigation of disorders such as fecal
      incontinence, constipation, irritable bowel syndrome, and chronic intestinal
      pseudo-obstruction.

PMID- 7644051
TI  - Headache and neck pain in spontaneous internal carotid and vertebral artery
      dissections.
AB  - We studied the characteristics of headaches in 161 consecutive symptomatic
      patients with spontaneous dissections of the internal carotid artery (n = 135) or
      the vertebral artery (n = 26). For patients with internal carotid artery
      dissection (ICAD), the mean age was 47 years and for those with vertebral artery
      dissection (VAD), 40.7 years. A history of migraine was present in 18% of the
      ICAD group and in 23% of the VAD group. Headache was reported by 68% of the
      patients with ICAD and by 69% of those with VAD, and, when present, it was the
      initial manifestation in 47% of those with ICAD and in 33% of those with VAD. Ten
      percent of patients with ICAD had eye, facial, or ear pain without headache. The
      median interval from onset of headache to development of other neurologic
      manifestations was 4 days for the ICAD group and 14.5 hours for the VAD group.
      For all dissections, headaches typically were ipsilateral to the side of
      dissection. In the ICAD group, headaches were limited to the anterior head in 60%
      of patients and were steady in 73% and pulsating in 25%. In the VAD group,
      headaches were distributed posteriorly in 83% of patients and were steady in 56%
      and pulsating in 44%. Neck pain was present in 26% of patients with ICAD
      (anterolateral) and in 46% of those with VAD (posterior). The median duration of
      the headache in patients with VAD and ICAD was 72 hours, but headaches became
      prolonged, persisting for months to years, in four patients with ICAD.

PMID- 7644052
TI  - The effect of nimodipine on essential tremor.
AB  - We investigated the effect of nimodipine (30 mg qid) in 16 de novo patients with
      essential tremor in a double-blind placebo-controlled study in which we assessed
      tremor by clinical scorings, tremorgraphic recordings, and patient self
      evaluation. Of the 15 patients who completed the study, eight improved. We
      conclude that nimodipine is effective in some patients with essential tremor.

PMID- 7644053
TI  - Proton magnetic resonance spectroscopic imaging in childhood ataxia with diffuse
      central nervous system hypomyelination.
AB  - The spatial distribution of metabolite signal intensities can be measured within
      entire sections of the brain by proton magnetic resonance spectroscopic imaging
      (1H-MRSI). A group of six patients (4 unrelated girls and 2 brothers from 5
      families) with childhood ataxia with diffuse CNS hypomyelination (CACH) underwent
      long-echo-time, single-slice 1H-MRSI. Relative to controls, there was a decrease
      in the signal intensity of N-acetylaspartate, choline, and creatine throughout
      the white matter in all six patients. We identified lactate signals in white
      matter in three of them with advanced disease. The degree of white matter
      involvement was not homogeneous over the entire patient group, but did correlate
      with clinical presentation. Deep and posterior white matter tended to be more
      involved. There were no 1H-MRSI abnormalities in the gray matter. 1H-MRSI
      findings suggest that this syndrome is secondary to a metabolic defect causing
      hypomyelination, axonal degeneration, and, in the most compromised cases,
      accumulation of lactate. This study shows that CACH is not limited to girls.

PMID- 7644054
TI  - Gene transfer of wild-type p53 results in restoration of tumor-suppressor
      function in a medulloblastoma cell line.
AB  - The replacement of functional genes into cells that lack genes or have mutant
      genes is the basis of gene therapy. In cancer, where cells often have multiple
      genetic defects, the replacement of critical genes may suffice to suppress cell
      growth or induce cell death. The high frequency of mutations of the p53 tumor
      suppressor gene in human cancers, including primary brain tumors, suggests that
      p53 plays a critical role in carcinogenesis and tumor progression. We report the
      successful transfer of the wild-type p53 gene using a defective herpes simplex
      viral vector into a human medulloblastoma cell line containing a mutant copy of
      p53. Upon gene transfer, we detected novel expression of wild-type p53 protein in
      the cells. In addition, the p53 protein was functionally active, since gene
      transfer resulted in increased levels of mdm2 proteins and induced cell cycle
      arrest of the majority of transduced cells. To our knowledge, this is the first
      report of the use of this vector system to carry wild-type p53. We conclude that
      defective herpes simplex viral vectors can transfer and express p53 in human
      primary brain tumor cells in vitro, restoring wild-type p53 tumor-suppressor
      functions.

PMID- 7644055
TI  - Localization of a cerebellar timing process using PET.
AB  - We used positron emission tomography (PET) to localize a cerebellar timing
      function. Six healthy volunteers estimated time differences by comparing a test
      interval (defined by two tones) with a standard interval. In the timing
      condition, subjects lifted their right index finger if the test interval was
      shorter and their right middle finger if it was longer than the standard
      interval. In the control condition, the two intervals were identical and subjects
      had to alternate between lifting their index and middle fingers. We examined
      regional cerebral blood flow (rCBF) using the standard C15O2 inhalation
      technique. Comparison of control and rest conditions revealed significant
      increases of rCBF during the control condition in the inferior parts of the
      ipsilateral cerebellar hemisphere, reflecting finger movements. Comparison of
      timing and control conditions showed additional activations of the cerebellar
      vermis and hemispheres bilaterally during the timing condition, reflecting the
      cerebellar timing process. We conclude that the cerebellum is involved in time
      critical perception ("timing"). This nonmotor task can be separated from a motor
      task (finger movement).

PMID- 7644056
TI  - Amnesia following traumatic bilateral fornix transection.
AB  - There is controversy regarding the effect of isolated fornix damage on human
      memory. We report a patient who suffered a traumatic penetrating head injury that
      resulted in a significant and persistent anterograde amnesia. CT revealed a
      lesion that involved the region of the proximal, posterior portion of both
      fornices without evidence of damage to other hippocampal pathways or to other
      structures known to be critical for memory, such as the hippocampus, thalamus, or
      basal forebrain. The unique location of the lesion in this patient provides
      evidence supporting the role of isolated fornix lesions in amnesia.

PMID- 7644057
TI  - Diagnostic value of GM1 antibodies in motor neuron disorders and neuropathies: a
      meta-analysis.
AB  - We performed a meta-analysis on the diagnostic value of IgM anti-GM1 antibodies.
      The reported frequencies of IgM anti-GM1 antibodies ranged from 0 to 100% for
      patients with multifocal motor neuropathy (MMN), from 0 to 33% in the Guillain
      Barre syndrome, from 0 to 65% in amyotrophic lateral sclerosis (ALS), from 0 to
      77% in chronic inflammatory demyelinating neuropathy, and from 0 to 81% in lower
      motor neuron disease (LMND). However, using funnel graphs and a chi-square test
      we determined that the method of ELISA was the most important factor explaining
      these differences. After allowing for two factors--the use of detergent and the
      duration and temperature of serum incubation-studies became homogeneous in all
      but the LMND group of method A (no detergent, duration of serum incubation 5
      hours) and the ALS group of method B (no detergent, duration of serum incubation
      at least 12 hours [overnight]). Since the anti-GM1 antibody assay serves to
      confirm clinical suspicion of MMN rather than to exclude the disease, specificity
      is more important than sensitivity. ELISA methods that do not use detergent and
      that incubate serum overnight resulted in a specificity of 90% and sensitivity of
      38% in the comparison of MMN and LMND. With these values we calculated
      incremental ruling-in and ruling-out gain curves. Prior probabilities between 20
      and 60% for having MMN changed to post-test probabilities between 50 and 85%,
      which is of clinical importance. In conclusion, ELISA is a useful diagnostic test
      to demonstrate IgM anti-GM1 antibodies provided the methods do not use detergent
      and do incubate serum overnight.

PMID- 7644058
TI  - Pervasive neuroanatomic abnormalities of the brain in three cases of Rett's
      syndrome.
AB  - Rett's syndrome (RS) is a clinically defined disorder that appears to be unique
      to girls and is characterized by apparent cognitive and motor skill loss early in
      life. We report our findings in the brains of three girls with RS, which were
      studied in comparison with age-matched controls by means of gapless serial
      section. Reduced neuronal cell size and increased cell-packing density were
      present throughout the cortical and subcortical regions of the brain in all cases
      without evidence of active degeneration. These observations appear to be
      consistent with a curtailment of development. Further, the degree of abnormality
      in each case correlates more closely with the clinical presentation of the
      patient at the time of death than with the age of the patient or duration of
      symptoms.

PMID- 7644059
TI  - Elevated thiobarbituric acid-reactive substances and antioxidant enzyme activity
      in the brain in Alzheimer's disease.
AB  - We determined levels of thiobarbituric acid-reactive substances (TBARS), a
      measure of lipid peroxidation, and the activity of the antioxidant enzymes
      superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione
      reductase (GSSG-R), and catalase (CAT) in the amygdala, hippocampus, pyriform
      cortex, superior and middle temporal gyri, inferior parietal lobule, middle
      frontal gyrus, occipital pole, and cerebellum of 13 Alzheimer's disease (AD) and
      10 control brains. Levels of TBARS were elevated in all AD brain regions except
      the middle frontal gyrus, and elevation levels reached statistical significance
      in the hippocampus and pyriform cortex and marginal significance in the amygdala
      of AD subjects compared with age-matched controls. Significant elevation of GSH
      Px activity was present in AD hippocampus compared with control. Moderate but
      statistically insignificant elevations of GSH-Px activity also were present in
      the amygdala and pyriform cortex in AD. GSSG-R activity was significantly
      elevated in the amygdala and hippocampus in AD subjects compared with controls.
      CAT activity was significantly elevated in AD hippocampus and superior and middle
      temporal gyri. SOD levels were elevated in all brain regions in AD patients
      compared with controls, although none of these elevations reached statistical
      significance. Antioxidant enzyme activities were significantly elevated where
      lipid peroxidation was most pronounced, suggesting a compensatory rise in
      antioxidant activity in response to increased free radical formation. This study
      supports the concept that the brain in AD is under increased oxidative stress and
      demonstrates that the oxidative changes are most pronounced in the medial
      temporal lobe, where histopathologic alterations are most severe.

PMID- 7644061
TI  - 'Anesthesia paresthetica': nitrous oxide-induced cobalamin deficiency.
AB  - A man with a subclinical cobalamin deficiency developed syncope, vertigo,
      paresthesias, and ataxia after two exposures to nitrous oxide anesthesia.
      Patients with unrecognized cobalamin deficiency may be particularly susceptible
      to brief exposures to nitrous oxide, which inactivates the cobalamin-dependent
      enzyme methionine synthase and may cause a myeloneuropathy. Clinicians should
      consider this entity when confronted with patients with neuropathic symptoms
      after surgical or dental procedures.

PMID- 7644060
TI  - Sudomotor function in human poikilothermia.
AB  - Hypohidrosis predisposes to hyperthermia and may indicate generalized
      thermoregulatory failure. To assess the sweating capacity in human
      poikilothermia, we performed a quantitative analysis of the central and
      peripheral sudomotor pathways in four women with acquired poikilothermia (aged 29
      to 38 years) and nine controls. Heat challenge in a climatic chamber (ambient
      temperature 40 degrees C, 50% relative humidity) for 180 minutes revealed that
      both sweat secretion and evaporative weight loss were significantly lower in the
      patients than in the controls (p < 0.01). Temperature thresholds for thermal
      sweating were markedly elevated in at least two patients, whereas a third patient
      showed no sweating response. Stimulation of the eccrine sweat glands by
      intradermally injected acetylcholine during reduced core temperature (34.9 +/-
      0.7 degrees C) revealed a significantly reduced sweating response in all patients
      (p < 0.01); the sudomotor response to pilocarpine iontophoresis was reduced or
      absent in three patients. We conclude that the generalized thermoregulatory
      sudomotor failure in these patients was attributable primarily to disorders of
      the central sudomotor drive; the impaired postganglionic sudomotor response is
      temperature related and possibly secondary to (long-standing) poikilothermia.
      Quantification of heat-dissipating capacity is pivotal for diagnosing severe
      thermolability and may help to prevent serious heat illness.

PMID- 7644062
TI  - Ischemic cerebrovascular disease and hormone therapy for infertility and
      transsexualism.
AB  - To highlight an emerging risk factor for stroke in the young, we report two
      patients who experienced ischemic cerebrovascular symptoms in unusual clinical
      settings of hormone therapy. Expanding indications for estrogenic therapy,
      including infertility and gender identity disorders, may constitute an emerging
      risk factor for ischemic stroke in young individuals.

PMID- 7644063
TI  - Long-duration response to levodopa.
AB  - We measured the long-duration response to levodopa by changes in tapping rate in
      16 patients with Parkinson's disease undergoing 3 to 5 days of levodopa
      withdrawal. "Off" tapping rates deteriorated 22% over the course of this holiday,
      the decline beginning 24 hours after levodopa withdrawal. Deterioration was more
      pronounced in the more affected hand in asymmetrically affected patients. A 2
      hour infusion of levodopa after the levodopa holiday did not restore the long
      duration response, although it produced a greater short-duration response than
      before the holiday. These observations indicate that the long-duration response
      is an important component of the therapeutic benefit of levodopa and is separable
      from the short-duration response.

PMID- 7644064
TI  - Aphasia secondary to partial status epilepticus of the basal temporal language
      area.
AB  - We present a patient with aphasia of several days' duration that was secondary to
      spontaneous partial status epilepticus arising from the left basal temporal
      region. Evidence from MRI, EEG, and PET confirmed the origin of the seizures in
      the basal temporal area. Both the seizure discharges and the aphasia resolved
      after antiepileptic therapy. This case, to our knowledge, is the first documented
      example of epileptic aphasia secondary to spontaneous partial status epilepticus
      originating from the basal temporal area.

PMID- 7644065
TI  - Ictal amaurosis: MRI, EEG, and clinical features.
AB  - We studied seven consecutive patients who experienced amaurosis as a prominent
      feature of their seizures. The mean age of seizure onset was 4 years. Six
      patients had MRI abnormalities including ischemic, traumatic, and space-occupying
      lesions, with five limited to the parietal-occipital region. Six patients had
      unilateral, posterior interictal spike and slow wave complexes. Four patients
      experienced severe postictal headache and nausea. Absence of a family history of
      seizures distinguished the patients with MRI lesions from previously presented
      series of benign occipital lobe epilepsy. We conclude that the constellation of
      ictal amaurosis, occipital paroxysms, and postictal migrainous symptoms does not
      necessarily signify a benign, nonlesional epilepsy; MRI is recommended for such
      patients without a family history of similar seizures.

PMID- 7644066
TI  - Antisulfatide antibody and neuropathy in a patient with Gaucher's disease.
AB  - We report the presence of antisulfatide antibodies in a patient with type I
      Gaucher's disease and peripheral neuropathy. The association of Gaucher's disease
      with hypergammaglobulinemia and monoclonal gammopathy is well documented whereas
      its association with peripheral neuropathy is rare. We discuss whether antibodies
      directed against the sulfatide antigen are related to Gaucher's disease or are a
      coincidental association.

PMID- 7644067
TI  - Reading-induced absence seizures.
AB  - Reading epilepsy usually presents with jaw myoclonus and generalized tonic-clonic
      seizures. We report a 12-year-old girl with absence seizures induced by reading,
      which were diagnosed by video EEG. An absence seizure with generalized 3-Hz spike
      and-wave discharge occurred within 30 seconds of each reading session. Treatment
      with valproate caused complete seizure control, with therapy successfully
      discontinued after 2 years.

PMID- 7644068
TI  - Myelitis due to coxsackievirus B infection.

PMID- 7644069
TI  - Acute isoniazid poisoning simulating meningoencephalitis.

PMID- 7644070
TI  - The restoration of IVIg efficacy by plasma exchange in CIDP.

PMID- 7644071
TI  - Unexpected recovery from anoxic-ischemic coma.

PMID- 7644072
TI  - Aspartame and headache.

PMID- 7644073
TI  - Aspartame and headache.

PMID- 7644074
TI  - Aspartame and headache.

PMID- 7644075
TI  - Motion perception in Alzheimer's disease.

PMID- 7644076
TI  - Motion perception in Alzheimer's disease.

PMID- 7644077
TI  - Environmental risk factors for Alzheimer's disease.

PMID- 7644078
TI  - Language dominance and MRI asymmetries.

PMID- 7644080
TI  - Oral sumatriptan for the long-term treatment of migraine: clinical findings.
AB  - This double-blind, placebo-controlled, crossover study of the acute treatment of
      migraine investigated the efficacy and tolerability of oral sumatriptan 100 mg
      (Imitrex) administered for up to nine attacks compared with placebo administered
      for up to three attacks. Patients were randomized to receive oral sumatriptan 100
      mg or placebo on an outpatient basis in a 3:1 ratio for three four-attack blocks.
      Headache relief 4 hours postdose was observed in 59 to 65% of patients after
      sumatriptan treatment compared with 18 to 23% of patients after placebo treatment
      across three four-attack blocks (p < 0.005). For each block, oral sumatriptan 100
      mg was also significantly more effective than placebo at relieving clinical
      disability and nausea and vomiting. Efficacy on all these measures was
      consistently maintained with repeated administration. Oral sumatriptan 100 mg was
      well tolerated, and repeated administration did not alter the pattern or severity
      of adverse events. These data demonstrate that the efficacy and tolerability of
      oral sumatriptan 100 mg was consistently maintained with repeated administration
      for up to nine separate migraine attacks.

PMID- 7644079
TI  - Oral sumatriptan is effective and well tolerated for the acute treatment of
      migraine: results of a multicenter study.
AB  - The efficacy and tolerability of oral sumatriptan (Imitrex tablets) were assessed
      in 187 migraineurs enrolled in a randomized, double-blind, parallel-group,
      placebo-controlled study. In the clinic, patients received oral sumatriptan 25
      mg, 50 mg, or 100 mg, or placebo, for the treatment of a migraine attack. The
      results demonstrate that by 2 hours postdose, 52 to 57% of patients treated with
      sumatriptan 25 mg, 50 mg, 100 mg compared with 17% of patients treated with
      placebo achieved relief of headache (p < 0.05 for each sumatriptan group vs
      placebo). By 4 hours postdose, 65 to 78% of sumatriptan-treated patients compared
      with 19% of placebo-treated patients achieved relief of headache (p < 0.05 for
      each sumatriptan group vs placebo). Oral sumatriptan also effectively relieved
      nausea and photophobia and improved clinical disability. No serious or unusual
      adverse events were reported, and the pattern and incidence of adverse events did
      not vary among the sumatriptan doses. Each dose--25 mg, 50 mg, or 100 mg--of
      sumatriptan was effective and generally well tolerated.

PMID- 7644081
TI  - Advances in migraine therapy: focus on oral sumatriptan.

PMID- 7644082
TI  - Oral sumatriptan for the acute treatment of migraine: evaluation of three dosage
      strengths.
AB  - This randomized, double-blind, parallel-group, placebo-controlled study evaluated
      the efficacy and tolerability of oral sumatriptan (Imitrex tablets) in 259
      migraineurs. In the clinic, patients received oral sumatriptan 25 mg, 50 mg, or
      100 mg, or placebo for the treatment of a migraine attack. The results indicate
      that by 2 hours post-dose, 50 to 56% of patients treated with any of the three
      doses, compared with 26% of patients treated with placebo, achieved relief of
      headache (p < 0.05 for each sumatriptan group vs placebo). By 4 hours postdose,
      68 to 71% of sumatriptan-treated patients, compared with 38% of placebo-treated
      patients, achieved relief of headache (p < 0.05 for each sumatriptan group vs
      placebo). Oral sumatriptan was similarly effective at relieving nausea and
      photophobia and at reducing clinical disability. The pattern and incidence of
      adverse events did not differ between treatment groups. All doses--25 mg, 50 mg,
      and 100 mg--of sumatriptan were effective and generally well tolerated. Dosing
      should be individualized according to the needs of the patient.

PMID- 7644083
TI  - Reducing heart disease: an international health priority. A growing body of
      evidence highlights the central role of lipids.

PMID- 7644084
TI  - [Intimal hyperplasia following vascular procedure. An unresolved problem].
AB  - Many pathophysiological mechanisms have been postulated for the development of
      intimal hyperplasia following arterial reconstructions that can lead to
      restenosis. The central theme appears to be injury to the endothelial cell. A
      number of pharmacological therapies have been proposed for the control of intimal
      hyperplasia, but at the current time this is managed by surgical reconstruction.
      Modification of the hyperplastic response by the newer pharmacological therapies
      requires further experimental and clinical studies. The definition of specific
      factors responsible for particular cellular events in the injured artery will
      make the right pharmacological treatment possible.

PMID- 7644085
TI  - [Identification of patients at risk of post-infarction heart rupture. Clinical
      and therapeutic characteristics of 121 consecutive cases and review of the
      literature].
AB  - In patients with acute myocardial infarction (AMI) since a decrease of deaths due
      to arrhythmia control and pump failure, rupture of the left ventricle free wall
      (RPL) has gained increasing importance as a cause of death. Of 4987 patients
      hospitalised for AMI from January 1969 to December 1993, RPL occurred in 121
      patients (2.4%) and 17.6% of total deaths from AMI are the result of this
      complication. RPL was found more often in women > 75 years old, with a history of
      hypertension and sustaining a first coronary event. Cardiac rupture occurred
      after transmural myocardial necrosis, usually (60%) following an anterior AMI.
      RPL was an early phenomenon (in 40% it occurred within the first 24 hours and in
      more than 80% within 5 days from symptoms onset). Although RPL is widely
      considered catastrophic and unexpected, in the greater number of patients it is
      possible to recognise symptomatic markers (pain, emesis and agitation) indicative
      of impending rupture. A prompt diagnosis and the consideration that rupture is
      usually a stuttering process must point out an aggressive approach, which can
      allow a surgical treatment of RPL with a likely prognosis.

PMID- 7644086
TI  - [Proximal anastomotic pseudoaneurysms].
AB  - Abdominal aortic pseudoaneurysms development in patients submitted to
      endoaneurysmectomy or bifurcated aorto-peripheral by pass was, for a long time,
      considered a rare complication of aortic surgery. In old papers it was referred
      prevalence of abdominal PSA which rambled on values less than 1%. The diagnosis
      was always reached in concomitance with fissurations, ruptures or aorto-digestive
      fistulas. Recent papers, in which were reported results of accurate instrumental
      (echo and TC) follow-up of patients with aortic prosthesis, demonstrated a really
      higher prevalence of abdominal aortic pseudoaneurysms (about 6%). A retrospective
      analysis of PSA admitted to the General and Cardiovascular Institute of the
      University of Milan and the First Surgical Division of the General Hospital of
      Treviglio-Caravaggio (BG), demonstrated a high morbidity and mortality of
      complicated aortic pseudoaneurysms surgery. Considering the data reported in the
      international literature and the results of the surgery of complicated aortic
      PSA, the Authors point out the necessity of accurate periodical instrumental
      follow-up of subjects with aortic prosthesis in order to identify anastomotic
      pseudoaneurysm and to evaluate incidental evolution of aneurysmatic disease.

PMID- 7644087
TI  - [Estrogens, left ventricular function and coronary circulation: what are the
      possibilities of therapeutic use?].
AB  - Low-dose estrogen replacement therapy should be recommended to post-menopausal
      women, especially if they suffer from circulatory disorders, because it
      significantly reduces cardiovascular risk. Low-dose estrogens favourably affects
      lipid profile, without causing a significant increase of thrombotic risk:
      atherosclerosis is therefore prevented. Estrogen can augment coronary flow by the
      relaxation of vascular smooth-muscular cells. Finally, estrogen can improve left
      ventricle systolic and diastolic function, delaying the physiological aging
      process.

PMID- 7644088
TI  - [Cross-over study on the effects of ketanserin vs enalapril in the treatment of
      hypertension].
AB  - The aim of the study was to compare antihypertensive efficacy and safety of
      ketanserin with those of enalapril in the treatment of hypertension. The study
      design was controlled, cross-over, with randomized sequences. The efficacy was
      evaluated from data of 19 (9 males, 10 females) mean age 59.5 +/- 10.1 years,
      weight kg 68 +/- 12.1 with hypertension lasting over 5 years. Posology was
      ketanserin 20-40 mg bid, and enalapril 10-20 mg bid; both for three weeks. The
      efficacy was good with both treatments and the effects similar. In fact, at the
      end of the treatment with ketanserin, supine SBP was decreased 10 +/- 20 and DBP
      5 +/- 10 mmHg, standing SBP was reduced 15 +/- 19 and DBP 7 +/- 15 mmHg. With
      enalapril supine SBP decreased 25 +/- 16 and DBP 10 +/- 13 mmHg, standing SBP was
      reduced 16 +/- 19 and DBP 8 +/- 18 mmHg. Changes of heart rate by either
      treatment were of no clinical importance. The safety of treatment with ketanserin
      was excellent, while 14.3% of the patients treated with enalapril had undesirable
      effects.

PMID- 7644089
TI  - [Splenic abscess after angiography. Considerations on a clinical case].
AB  - A case of splenic abscess in a diabetic, cardiopathic and arteriopathic 49-year
      old man is reported. The abscess developed on a previous splenic infarction
      caused by an embolus coming from an intraventricular thrombus. The angiographic
      procedure was the source of bacterial contamination (Staphylococcus aureus). The
      patient was successfully treated with splenectomy.

PMID- 7644090
TI  - [Considerations on the pathogenesis, diagnosis and therapy of renal venous
      aneurysm].
AB  - An aneurysms of a renal vein is very uncommon an entity and even more so when a
      visceral vein is affected. The venous aneurysms are generally asymptomatic and
      are detected either at post-mortem examination or by Echography, CT scan or MR
      investigation. Occasionally they become symptomatic because of rupture,
      thrombosis and embolism, but even in those cases they are difficult to be
      diagnosed and can be life threatening particularly when bleeding occurs.
      Exceptionally an aneurysm of a visceral vein is an unexpected intraoperative
      finding and is detected during an abdominal procedure undertaken for other
      pathology. In our experience a true aneurysm of the main trunk of the left renal
      vein was detected during a procedure of aorto-bifemoral by-pass graft repair for
      chronic aorto-iliac occlusive disease. The aneurysm was resected and the vein
      repaired by direct suture. Congenital weakness of the vein wall was very likely
      the cause as suggested by the extreme thinness and media atrophy of the aneurysm
      and normal appearance of the wall of renal vein and inferior vena cava.
      Differences between varices and aneurysms of the renal veins are discussed as
      well as indications for surgical treatment.

PMID- 7644091
TI  - [How does casual arterial pressure compare to monitored arterial pressure?].

PMID- 7644094
TI  - [Sports and adolescence: the effect of competitive athletics on menstrual
      function].
AB  - A group of 381 girls, 12 up to 19-years-old, engaging in competitive sports
      (athletics, basketball, dancing, gymnastics, swimming, ski-ing, tennis, volley
      ball) was examined. Age at menarche and menstrual characteristics were correlated
      with the body weight, the competitive practice start age, the kind of the sport
      and the amount of training hours/week. Collected data were compared with the ones
      from a pool of 387 girls of equivalent mean age, not playing any sport. Delay of
      menarche and larger frequency of menstrual disorders, found among athletes,
      turned out to be directly proportional to the amount of time devoted to training
      and to the kind of performed sports. Irregular cycles are more frequent in
      athletes having a normal or lower body weight and do not normalise proceeding in
      sporting activities.

PMID- 7644092
TI  - [Parvovirus B19 infection: the general aspects and gestational problems].
AB  - Parvovirus B19 is a small, heat-stable, single-strained DNA virus (5.5 kb), with
      23 nm icosahedral capsid discovered in 1975. Since its discovery, the virus has
      been shown to be a causative agent of erythema infectiosum (fifth disease). Under
      specific circumstances it can cause transient aplastic crisis, chronic anemia,
      arthritis and fetal death. Laboratory diagnosis of recent or past B19 infection
      usually relies on the demonstration of virus-specific IgM or IgG antibodies in
      patient's serum. The aim of this study was to evaluate the prevalence of
      Parvovirus B19 infection among 87 pregnant patients. Our study on anti-B19
      antibody prevalence indicates that about 64% of pregnant women in our country
      lack specific antibodies and are at risk of B19 infection. One intrauterine death
      was encountered in a patient with specific IgM antibodies. The authors suggest
      the detection of IgG and IgM anti-B19 antibodies as a routine screening practice
      during pregnancy.

PMID- 7644093
TI  - [The weekly growth variations of the principal fetal echographic biometric
      parameters in pregnancy].
AB  - The aim of this study was to describe the normal range for the measurement of
      sonographic fetal parameters in our population, analyzed growth trend in
      different periods of pregnancy and establish the optimal time interval between
      scans. The study was performed in 2336 normal pregnant women between 14-40 weeks
      of gestation. Polynomial regression analysis was used to describe growth curves.
      A persistent increment of all ultrasonographic parameters throughout pregnancy
      was observed with a very high correlation with gestational age. A flattening of
      growth curves was observed after the 30th week of gestation for cephalic
      parameters and after the 28th week for the other parameters, particularly for
      fetal limb measurements. Considering inter- and intra-operator error and the
      physiological weekly increment, a correct growth evaluation of single parameters
      requires at last a two weeks time span from the last scan performed. Only the
      biparietal diameter and femur length allow a correct growth evaluation weekly,
      before the 30th week and the 28th week, respectively.

PMID- 7644095
TI  - [The use of an automatic stapler in abdominal hysterectomies. Our experience].
AB  - One hundred and four patients were randomized into two groups: group 1 (n = 56)
      included patients in whom used absorbable staples in vaginal cuff closure; group
      2 (n = 48) included patients with classical abdominal hysterectomy. Operating
      time, facility and outcome 6 months later, were evaluated. Greater costs of
      absorbable staples compared with sutures can readily be counterbalanced by saving
      allowed by shorter operating time, no peritoneal contamination, minimal tissue
      trauma and better cuff healing.

PMID- 7644096
TI  - [The treatment with intramuscular interferon of female genital condylomatosis:
      beta-IFN vs alfa-2a-IFN].
AB  - The authors have investigated the efficacy of i.m. therapy with interferon (IFN)
      in the treatment of female genital condylomatosis: 94 consecutive patients
      underwent a randomized therapy with two different IFNs: beta-IFN and alpha-2A-IFN
      (3,000.000 UI i.m. on alternate days for 4 weeks). A total and/or partial
      response was observed in 76.5% of cases (72/94). Observed response was unrelated
      with used IFN, independently of type and seat of treated lesion. There was only
      an important difference between the two treatments in the incidence of side
      effects and drop-out (31% and 6.3% with alpha-2A-IFN and 14.8% and 2.1% with beta
      IFN). Systemic therapy with IFN is a good alternative to destructive techniques
      in the treatment of HPV-associated pathology of female lower genital tract.

PMID- 7644097
TI  - [Endometriosis of the sigmoid: 2 new cases and a review of the literature].
AB  - Endometriosis of the sigmoid colon is a pathology which is not frequently
      reported but may be manifested with symptoms in the form of intestinal occlusions
      and/or subocclusions and rectorrhagia. Diagnosis is difficult because there are
      no typical radiological and endoscopic findings. The authors report two cases of
      sigmoid endometriosis which were manifested by recurrent subocclusive attacks and
      rectorrhagia. Moreover, they stress the rarity of the site and review the
      literature in order to summarise the etiopathogenetic hypotheses and
      anatomopathological aspects. They also focus on clinical symptoms and on
      endoscopic and radiological findings. Lastly, they examine the problems of
      differential diagnosis and the therapeutic options.

PMID- 7644098
TI  - [A case of umbilical endometriosis following cesarean section].
AB  - Umbilical endometriosis is a rare pathology whose etiopathogenesis is still
      uncertain and the theories put forward are all controversial. Diagnosis is
      therefore frequently difficult. The authors report a case of umbilical
      endometriosis which occurred in a scar left by an earlier cesarean section.
      Moreover, they discuss the aspects which might facilitate the diagnostic approach
      and a correct therapeutic management.

PMID- 7644099
TI  - European Erythropoietin Symposium: Moving into the Second Decade of Clinical
      Experience in CRF. Seville, Spain, 11-13 November 1994.

PMID- 7644100
TI  - Erythropoietin and the anaemia of chronic disease.
AB  - The anaemia of chronic disease is the second most common anaemia in the world and
      is an underproduction anaemia with relatively low erythropoietin (EPO) values for
      the degree of the anaemia. This anaemia occurs with inflammation, infection, or
      malignancy and a principle question has been whether it would respond to
      recombinant human EPO (r-HuEPO). Several studies are now available to answer this
      question. In one study 12 of 16 patients with rheumatoid arthritis receiving r
      HuEPO increased their haematocrits 6 percentage points or more and 11 of 12
      reached normal haematocrits. Investigations of the effect of r-HuEPO on the
      anaemia of AIDS showed that patients with EPO levels of 500 U/L or less had an
      increase in the mean haematocrit of 4.6 percentage points with a decrease in red
      cell transfusions from 5.3 to 3.2 units per patient. Quality of life indices
      significantly improved in responders. When 413 patients with anaemia due to a
      wide variety of malignancies were randomized to r-HuEPO treatment, 58% of those
      receiving chemotherapy increased their haematocrits by at least 6 points over 12
      weeks. Quality of life parameters of responders also significantly improved.
      Anaemia in three patients with inflammatory bowel disease also responded in 8-14
      weeks to r-HuEPO and two of the three reached normal haemoglobin levels. It is
      clear that r-HuEPO can correct the anaemia of chronic disease and can improve the
      quality of life of responders.

PMID- 7644101
TI  - Regulation of the erythropoietin gene.

PMID- 7644102
TI  - Erythropoietin receptor: application in drug development.
AB  - Erythropoietin (EPO) is the primary hormone responsible for the growth and
      maturation of red blood cells in mammals. In contrast to many other growth
      factors, the specificity of EPO for mature erythroid cells has lead to its
      development as a safe and efficacious therapeutic, EPREX. The medical benefits of
      EPREX have been well established in the treatment of anaemic chronic renal
      failure patients, anaemic HIV patients treated with AZT, cancer chemotherapy
      patients, and patients wishing to donate their own blood prior to elective
      surgery (autologous predonation). Due to the chronic nature of EPO therapy, it
      would be desirable to have an orally administered 'second generation' molecule.
      An understanding of the structural basis of the interaction of EPO with its
      receptor will aid in the design of an oral anaemia drug. In this study, a series
      of mutations have been generated in a truncated form of the receptor comprising
      the extracellular region, termed EPO binding protein (EBP). One mutant, in which
      alanine replaces phenylalanine at position 93 (F93A) has a 500-fold reduction in
      binding compared to wild-type EBP. A neutralizing anti-EBP antibody binds poorly
      to the F93A mutant, while a non-neutralizing anti-EBP antibody binds wild-type
      and F93A equally well. Information from this mutational analysis can be applied
      to a receptor 3-D model and ultimately used in drug development.

PMID- 7644103
TI  - Historical review on the use of recombinant human erythropoietin in chronic renal
      failure.
AB  - The success of maintenance haemodialysis in the 1960s was blighted by the problem
      of anaemia. Treatment with iron, folic acid, androgens and transfusions did no
      more than minimize its effects. The need for a renewable source of erythropoietin
      was appreciated very early but the hope took 25 years to realize. Cloning and
      expression of the human gene was achieved in 1984 and clinical trials planned
      even before the descriptions of the recombinant hormone were published. The Amgen
      material was tested in parallel studies in Seattle and England and by the end of
      1986 the efficacy of recombinant human erythropoietin (r-HuEPO) given in large
      intravenous bolus doses in reversing the anaemia of uraemia was established. The
      benefits were immediately obvious: relief from transfusion dependence was the
      unequivocal evidence but the effect on 'wellbeing' though subjective was
      remarkable. Large clinical trials were completed in Europe and the USA so that r
      HuEPO was licensed as a therapeutic drug less than two years later. The pilot
      studies flagged a number of key issues: hypertension, sometimes with
      encephalopathy, occurred in patients whose blood pressure was labile before
      treatment; vascular access failure seemed more frequent and hyperkalaemia was
      thought to reflect less efficient dialysis. Failure to respond focused attention
      on iron balance as well as on factors such as infection, aluminium, and
      hyperparathyroidism. A more clear understanding of the pathogenesis of the
      anaemia of uraemia was made possible by dissection of the specific effects of the
      exogenous erythropoietin on erythroid function.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7644104
TI  - Starting r-HuEPO in chronic renal failure: when, why, and how?

PMID- 7644105
TI  - Starting r-HuEPO in chronic renal failure: when, why, and how?
AB  - Administration of recombinant human erythropoietin (r-HuEPO) in uraemic pre
      dialysis patients is both effective and safe. The benefits are similar to those
      in dialysis patients: a marked increase in subjective wellbeing and ability to
      perform physical work. There is a strong argument for treating on the basis of
      anaemic symptoms, rather than on absolute haematocrit or haemoglobin. Some 30-40%
      of r-HuEPO-treated pre-dialysis patients may need initiation of, or an increase
      in, antihypertensive therapy. Provided blood pressure is carefully controlled, r
      HuEPO does not appear to accelerate the progression of renal failure, and there
      is preliminary evidence that it may even delay the need for dialysis in children
      and possibly in adults. Subcutaneous self-administration is convenient for most
      pre-dialysis patients; once weekly administration can yield effective results and
      may enhance patient compliance. As in dialysis patients, detection and correction
      of iron deficiency play an essential role in maximizing the success of r-HuEPO
      administration. For most pre-dialysis patients, oral iron administration is
      convenient, and absorption is satisfactory.

PMID- 7644106
TI  - Haemoglobin--is more better?
AB  - Quality of life is closely linked to our ability to meet the exercise challenges
      imposed on us by our daily round of activities and those we select as leisure
      time activities. Aerobic metabolism of fat and carbohydrates provides the energy
      to support our activities. An increase in aerobic capacity extends the range and
      duration of activities we can undertake without the premature onset of fatigue.
      An adequate oxygen delivery, especially to skeletal muscles, is central to the
      effective aerobic support of energy metabolism. Frequent exercise improves our
      aerobic capacity by a relatively modest increase in oxygen transport and a large
      improvement in the capacity of muscle to use oxygen delivered. This is achieved
      by an increase in mitochondrial density as well as an increase in capillarisation
      of skeletal muscles. A decrease in oxygen delivery, in active people, produces
      the same type of adaptive increases in aerobic capacity. Therefore, even though
      more haemoglobin is clearly better for active healthy individuals, frequent
      exercise can improve the capacity of renal patients to make the most effective
      use of their anaemia-imposed reduced oxygen delivery system.

PMID- 7644107
TI  - Haemoglobin--is more better?
AB  - Recombinant human erythropoietin (r-HuEPO) treatment reduces cardiac output and
      increases left ventricular mass: beneficial effects that might be expected to be
      maximized at near-normal haemoglobin values. Quality of life in dialysis patients
      treated with r-HuEPO has been shown to be related to haemoglobin, up to a
      haematocrit of 35%. The potential benefits of increasing the target haemoglobin
      must, however, be seen in the context of the haemodynamic changes that occur
      during r-HuEPO treatment, in particular, increased peripheral resistance (leading
      to hypertension), and possible adverse effects on the coagulation system and
      microcirculation. Pending further trials with a target haemoglobin of 14 g/dl or
      a haematocrit of 40%, a target haematocrit of 34-37% seems reasonable; it might
      also be appropriate to adjust the target haematocrit according to the
      individual's symptoms and lifestyle.

PMID- 7644108
TI  - R-HuEPO hyporesponsiveness--who and why?

PMID- 7644109
TI  - R-HuEPO hyporesponsiveness--who and why?
AB  - The most common cause of limited response to recombinant human erythropoietin (r
      HuEPO) is unrecognized, mild-to-moderate iron deficiency, either at the start of
      treatment or secondary to enhanced iron utilization by newly formed erythrocytes.
      Iron stores in patients with chronic renal failure (CRF) are often depleted
      through gastrointestinal bleeding, blood loss during haemodialysis, and blood
      sampling. Mobilization of iron stores may be inadequate, especially during rapid
      haemoglobin regeneration. Aluminium overload may also interfere with
      gastrointestinal and cellular iron uptake. Overt or unrecognized infection or
      inflammation is another common cause of hyporesponsiveness, and is a consequence
      of increased blood concentrations of cytokines such as tumour necrosis factor
      (TNF), interleukin-1 (IL-1), and interferon-gamma (IFN-gamma), which suppress
      erythrocyte stem-cell proliferation. Less common causes include severe secondary
      hyperparathyroidism and myeloma (during chemotherapy). Response to r-HuEPO can be
      best predicted by baseline fibrinogen (a marker of subclinical inflammation);
      baseline transferrin receptor (sTfR) concentrations (a marker of functional iron
      deficiency); and sTfR increment after 2 weeks (a marker of early change in
      erythropoietic activity).

PMID- 7644110
TI  - Erythropoietin and systemic hypertension.
AB  - Systemic hypertension has been reported to develop, or to worsen, in 20-30% of
      patients treated with recombinant human erythropoietin (r-HuEPO) worldwide. The
      greatest increases in blood pressure affect day-time systolic and night-time
      diastolic blood pressure. Hypertension may develop in some patients as early as 2
      weeks and in others as late as 4 months after the start of r-HuEPO treatment. In
      haemodialysis patients with systemic hypotension, r-HuEPO usually induces a 10%
      increase in blood pressure, with no significant change in the frequency of
      hypotensive episodes. Several risk factors for the development, or worsening, of
      hypertension after r-HuEPO therapy have been identified. They include the
      presence of pre-existing hypertension, rapid increase in haematocrit, a low
      baseline haematocrit before r-HuEPO administration, high doses and i.v. route of
      administration, the presence of native kidneys, a genetic predisposition to
      hypertension, and possibly a younger age. There are several potential mechanisms
      by which r-HuEPO therapy may increase blood pressure in haemodialysis patients.
      They include increased blood viscosity; the loss of hypoxic vasodilation; the
      activation of neurohumoral systems (catecholamines, the renin-angiotensin
      system); and especially a direct vascular effect. This last mechanism is
      supported by several data, and many factors may be involved in its pathogenesis
      (an increased cell calcium uptake; an imbalance in local vasoactive agents, with
      increased synthesis of ET-1; a mitogenic effect; and a platelet-dependent
      mechanism).

PMID- 7644111
TI  - Hypertension and cardiovascular effects--long-term safety and potential long-term
      benefits of r-HuEPO.
AB  - Systemic hypertension may develop, or worsen, in 20-30% of haemodialysis patients
      treated with recombinant human erythropoietin (r-HuEPO). No particular group of
      patients, however, should be excluded from r-HuEPO treatment because of this
      increased risk. In the vast majority of cases, hypertension can be managed
      effectively by reducing dry weight, and by adding an antihypertensive agent if
      necessary. Only if these approaches are ineffective should the dose of r-HuEPO be
      reduced. Patients on dialysis are likely to be intolerant of cardiac ischaemia,
      as a result of coronary artery disease, microvascular occlusive disease,
      inadequate neo-vascularization in cardiac hypertrophy, or reduced glucose uptake
      (which impairs non-oxidative metabolism of the heart). Treatment with r-HuEPO can
      significantly reduce cardiac risk, as measured by surrogate endpoints such as
      left ventricular hypertrophy. More studies are urgently needed to investigate the
      potential beneficial effects of r-HuEPO on hard endpoints such as cardiac
      morbidity and mortality. In addition, dose-response data for target haematocrits
      in the range 30-40% are needed before an appropriate target haematocrit can be
      determined for patients with symptomatic vascular and cardiac disease.

PMID- 7644112
TI  - How to get the best out of r-HuEPO.
AB  - Recombinant human erythropoietin (r-HuEPO) therapy is expensive, and it is
      therefore important to optimize its use to satisfy the health economist as well
      as the prescriber. Five main issues can be considered in helping to achieve this
      goal: (i) Route and site of administration. Much evidence suggests that
      subcutaneous (s.c.) administration of r-HuEPO is more cost-effective than
      intravenous (i.v.) administration, i.e. lower s.c. doses may be used to achieve
      the same effect. There are, however, some studies which suggest that there is
      little to choose between the two routes. One pharmacokinetic study in normal
      volunteers found that s.c. injection of r-HuEPO into the thigh resulted in
      greater peak values and greater bioavailability than s.c. injection into the arm
      or abdomen. (ii) Frequency of injection. There are now reports of dialysis
      patients being variously treated with once-weekly, twice-weekly, thrice-weekly,
      and once-daily s.c. administration of r-HuEPO. Despite some comparative studies,
      the optimum dosing frequency for s.c. r-HuEPO remains unclear. (iii) Iron status.
      Failure of an adequate supply of iron to the erythron is probably the most common
      and most easily treated cause of sub-optimal response to r-HuEPO. Effective and
      regular monitoring of iron status by measurement of serum ferritin, transferrin
      saturation, and per cent hypochromic red cells is critical to the management of
      the patient receiving r-HuEPO, and there is increasing evidence that liberal use
      of i.v. iron may enhance the response to this treatment. (iv) Other factors
      affecting response to r-HuEPO.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7644113
TI  - How to get the best out of r-HuEPO.
AB  - Inadequate iron supply is probably the most common and most easily treated cause
      of sub-optimal response to recombinant human erythropoietin (r-HuEPO). A low
      ferritin value is a reliable indicator of iron deficiency, provided that patients
      are in equilibrium (e.g. without infection, bleeding, vitamin or folate
      deficiency). Normal or high ferritin values do not necessarily preclude iron
      deficiency. Transferrin saturation is not always a reliable indicator of iron
      deficiency. The measure which best reflects iron supply to the erythron is the
      percentage of hypochromic red cells. Iron supplementation should be targeted at
      keeping serum ferritin > 100 micrograms/l, transferrin saturation > 20%, and
      hypochromic red cells < 10%. Iron status should be monitored monthly for the
      first few months after initiation of r-HuEPO, and thereafter at 2-3 month
      intervals. For haemodialysis patients, who have a very high rate of iron loss,
      i.v. iron administration is preferable and may also be appropriate for patients
      on continuous ambulatory haemodialysis (CAPD) and pre-dialysis patients. Recent
      studies with i.v. iron supplementation have shown no difference between the s.c.
      and i.v. routes of administration of r-HuEPO. Both the i.v. and the s.c. route
      are appropriate for patients on haemodialysis, whereas patients on CAPD or pre
      dialysis patients should receive s.c. r-HuEPO. The optimum frequency of s.c.
      administration in the vast majority of patients is 2-3 times weekly. For a small
      number of patients, once weekly s.c. administration may be suitable. When
      satisfactory haemoglobin values are reached, the dose of r-HuEPO should be
      titrated down gradually. It should not be stopped abruptly unless there are life
      threatening complications.

PMID- 7644114
TI  - The future of r-HuEPO.
AB  - Since the introduction of recombinant human erythropoietin (r-HuEPO) 9 years ago,
      there have been tremendous physiological improvements in patients with various
      anaemias due to absolute and relative erythropoietin (Epo) deficiencies. However,
      not all patients that could benefit from r-HuEPO are being treated, not all are
      responding who should be responding, and most dialysis patients (who comprise the
      single largest group of treatment recipients) are being inadequately treated. The
      future of r-HuEPO will depend upon whether clinicians can optimize the use of r
      HuEPO and determine what should be the optimal haematocrit. These issues will, in
      turn, depend upon whether three interdependent variables are addressed: the need
      for more scientific studies to evaluate various aspects of the use and
      effectiveness of r-HuEPO; the need for physician education to better understand
      the role of r-HuEPO in optimizing health in patients with anaemia in chronic
      renal failure and in the anaemia of chronic disease; and the need for less costly
      r-HuEPO therapy so that more patients can be treated and receive optimal therapy.
      Better use of r-HuEPO could result in significantly improved morbidity and
      perhaps improved survival of patients with Epo-deficient anemias.

PMID- 7644115
TI  - Paresthesia induced by cutaneous infection with herpes simplex virus in rats.
AB  - To assess the effects of herpetic infection on somatic sensations, herpes simplex
      virus type-1 was inoculated into the unilateral hind paw of the rat and its
      behavioral responses to noxious pressure and tactile stimulation were examined.
      Herpetic infection significantly increased the nociceptive threshold of the
      treated hind paw with a delay around 4 days. The increase in the nociceptive
      threshold continued at least until post-inoculation day 21 and was larger at
      night than in the morning. Any alterations in tactile responses were not observed
      during this period. Herpetic DNA was detected by polymerase chain reaction in the
      inoculated skin, but not in the dorsal root ganglia on the inoculated side, on
      the next day after inoculation. But on the following days it was detected in the
      dorsal root ganglia, but not in the skin. These results suggest that herpetic
      infection of the dorsal root ganglion produces paresthesia as a functional
      abnormality of the sensory neurons in rats.

PMID- 7644116
TI  - Thrombin and TGF-beta promote human leptomeningeal cell proliferation in vitro.
AB  - Some disorders of the central nervous system, such as trauma, meningitis, or
      subarachnoid hemorrhage (SAH), result in inflammation and fibrosis of the
      arachnoid membranes followed by hydrocephalus. To clarify the role of growth
      factors in the pathophysiology of arachnoid fibrosis, we investigated the
      response of leptomeningeal (LM) cells to growth factors elevated in the
      cerebrospinal fluid (CSF) of patients with subarachnoidal inflammation. We
      examined the proliferative responses of LM cells to thrombin, transforming growth
      factor-beta (TGF-beta), epidermal growth factor (EGF), acidic fibroblast growth
      factor (aFGF), platelet derived growth factor (PDGF), tumor necrosis factor-beta
      (TNF-beta) and interleukin 1-beta (IL1-beta). Thrombin, TGF-beta, EGF, aFGF and
      PDGF promoted LM cell proliferation. TGF-beta enhanced the proliferative effect
      of thrombin and EGF on LM cells. These findings suggest that thrombin and TGF
      beta, which may be elevated in CSF following SAH, may cause subarachnoid fibrosis
      and subsequent hydrocephalus.

PMID- 7644117
TI  - The effect of anosmia on MK-801-induced behaviour in mice.
AB  - Systemic administration of N-methyl-D-aspartate (NMDA) receptor antagonists
      induces a well defined behaviour in rodents characterized by, for example
      increased locomotion and ataxia. It is not clear in what brain region(s) NMDA
      antagonists induce this behaviour. We have studied the possible involvement of
      olfactory pathways by making adult mice anosmic via intranasal injection of zinc
      sulphate, a procedure that is known to destroy the olfactory epithelium. The NMDA
      antagonist MK-801 was given intraperitoneally (0.1-1.0 mg/kg) and the animals
      were scored for locomotion and ataxia 60-90 min later. Before MK-801
      administration, olfactory-lesioned mice did not differ from non-lesioned controls
      with regard to locomotion or ataxia. MK-801 caused locomotor activation (> or =
      0.2 mg/kg) and ataxia (> or = 0.5 mg/kg) in both groups. In general, olfactory
      lesioned animals showed more locomotion and less ataxia after MK-801
      administration than non-lesioned animals. Lesioned animals displayed 2.0- (P <
      0.05) and 3.7-fold (P < 0.05) more extensive locomotor activation than non
      lesioned animals after 0.5 and 1.0 mg/kg of MK-801, respectively. No difference
      in the degree of ataxia was seen between the two groups at 0.5 mg/kg, whereas non
      lesioned animals showed a 2.1-fold higher degree of ataxia after 1.0 mg/kg of MK
      801, indicating that the enhanced MK-801-induced locomotor activation in
      olfactory-lesioned mice was not simply due to less ataxia. These results suggest
      that olfactory input is involved in NMDA antagonist-induced behaviour.

PMID- 7644118
TI  - A role for calcitonin gene-related peptide in the regulation of rat skeletal
      muscle G4 acetylcholinesterase.
AB  - Calcitonin gene-related peptide (CGRP) acts as an anterograde trophic agent which
      regulates skeletal muscle acetylcholine receptor function. We examined whether
      CGRP also influences other synaptic transmission-related molecules, i.e.
      acetylcholinesterase (AChE) forms. Results show that: (a) CGRP associated with
      rat anterior gracilis muscle endplates declines following obturator nerve
      transection; (b) exogenous CGRP treatment has a selective, innervation-like
      effect on the globular tetramer (G4) of AChE in gracilis motor endplates; and (c)
      this effect is reversed by the CGRP receptor antagonist hCGRP8-37. We conclude
      that exogenous CGRP, and/or a biologically active CGRP fragment(s), influences G4
      AChE levels through specific CGRP-CGRP receptor interactions. This conclusion is
      consistent with the notion that motor nerve-derived CGRP participates in the
      trophic control of G4 AChE at the neuromuscular junction.

PMID- 7644119
TI  - Action of diphenylamine carboxylate derivatives, a family of non-steroidal anti
      inflammatory drugs, on [Ca2+]i and Ca(2+)-activated channels in neurons.
AB  - Ca(2+)-activated channels, including Ca(2+)-activated non-selective (CAN)
      channels and Ca(2+)-activated Cl- channels play important roles in regulating the
      electrical activity of neurons. No blockers of neuronal CAN channels have been
      previously reported. We used 2-electrode voltage clamping to measure membrane
      currents and fura-2 fluorescence imaging to measure [Ca2+]i in molluscan neurons.
      We show that the diphenylamine carboxylate derivative flufenamate (FFA), but not
      mefenamate or the parent compound, cause a transient increase in ICAN and a slow
      outward current, and a maintained increase in [Ca2+]i. We interpret this as a FFA
      dependent release of Ca2+ from intracellular stores and Ca2+ influx, [Ca2+]i
      dependent activation of the CAN and slow outward currents, and slow FFA-dependent
      channel block.

PMID- 7644120
TI  - Effects of arginine vasopressin and angiotensin II on area postrema neurons in
      rabbit brain slice preparation.
AB  - Previous in vivo studies have indicated that both arginine vasopressin (AVP) and
      angiotensin II (ANG II) can modulate the baroreflex by acting on the area
      postrema (AP). In the present study, effects of AVP and ANG II on AP neuronal
      activity were investigated by recording extracellular activity in a rabbit
      brainstem slice preparation. AVP (1 nM-1 microM) inhibited 14.5% and excited
      53.2% of the neurons while ANG II (1 nM-5 microM) inhibited 32.3% and excited 29%
      of the neurons. Application of AVP and ANG II to the same AP neurons at the same
      concentration indicated that more AP neurons responded to AVP than to ANG II. ANG
      II induced more inhibitory responses than AVP. The results suggest that AVP and
      ANG II may produce different effects on the baroreflex by acting on different
      pools of AP neurons and by exerting different effects on the same AP neuron.

PMID- 7644121
TI  - Suprachiasmatic nucleus and photoperiodic regulation of gonadal development in
      the Siberian hamster, Phodopus sungorus.
AB  - Photoregressed Siberian hamsters exposed at 19 days of age to constant light for
      24 h manifested increased testicular development 16 days later. Hamsters that
      sustained lesions of the suprachiasmatic nucleus (SCN) 3 days after the light
      pulse had significantly heavier gonads than did sham-operated animals or hamsters
      pinealectomized at 19 days of age. Enhanced reproductive development after SCN
      ablation is not due solely to lesion-induced elimination of melatonin secretion.
      SCN neural activity beginning 3 days after the light pulse is not necessary for
      light-induced gonadal growth.

PMID- 7644122
TI  - GABAB antagonists diminish the inhibitory gating of auditory response in the rat
      hippocampus.
AB  - Auditory evoked responses recorded from the CA3 region of the rat hippocampus
      show diminished response to repeated stimuli, suggesting the activity of an
      inhibitory gating mechanism. The effects on this putative gating mechanism of two
      GABAB receptor antagonists, CGP35348 and CGP46381, were characterized in a
      conditioning testing paradigm. Both compounds, administered
      intracerebroventricularly, antagonized the suppression of response to the test
      stimulus. The results are consistent with the hypothesis that this inhibitory
      gating of response involves GABAB receptors, which may control the release of
      glutamate from excitatory pathways in the hippocampus.

PMID- 7644123
TI  - Sigma antagonists potentiate opioid analgesia in rats.
AB  - In mice, activation of sigma1 receptors antagonizes opioid analgesia. Sigma
      antagonists potentiate opioid analgesia, implying that the anti-opioid sigma
      system is tonically active. Co-administration of haloperidol with the mu opioid
      morphine, the kappa 1 analgesic U50,488H or the kappa 3 agonist naloxone
      benzoylhydrazone enhances the analgesic activity of all agents. The effect
      results from sigma receptor blockade since (-)sulpiride, a selective D2
      antagonist which does not block sigma receptors, is inactive.

PMID- 7644124
TI  - GTP cyclohydrolase I activity in mononuclear blood cells in juvenile
      parkinsonism.
AB  - GTP cyclohydrolase I activity in mononuclear blood cells from patients with
      juvenile parkinsonism (JP) was found to be normal compared to healthy controls.
      The normal activity in JP contrasts strongly with the decreased activity of 2-20%
      normal levels in hereditary progressive dystonia with marked diurnal fluctuation
      (HPD) or dopa responsive dystonia (DRD). The result indicates that the decreased
      dopamine level in the basal ganglia in JP is not due to decreased activity of GTP
      cyclohydrolase I, the enzyme for the biosynthesis of the tetrahydrobiopterin
      cofactor of tyrosine hydroxylase (TH), and the enzyme activity in mononuclear
      blood cells could be a reliable method for differential diagnosis between JP and
      HPD/DRD.

PMID- 7644125
TI  - Serotonin involvement in the spontaneous alternation ability: a behavioral study
      in tryptophan-restricted rats.
AB  - Spontaneous alternation (SA) is controlled by septal cholinergic terminals in the
      hippocampus. Serotoninergic terminals end on cholinergic nerve endings in the
      hippocampus, and their possible role in SA was investigated in rats fed with a
      tryptophan-deficient diet, from weaning to 60 days of age. A T-maze was used for
      the test. At the age of 40 days, an increase in SA occurred in the tryptophan
      deficient rats, although this effect disappeared by 60 days of age. A modulatory
      role of serotonin in the psychoneural control of SA is suggested, and it may be
      through presynaptic inhibition of hippocampal cholinergic terminals.

PMID- 7644127
TI  - Regional cerebral blood flow responses to neurochemical stimulation of the
      substantia innominata in the anaesthetized rat.
AB  - Since electrical stimulation of neurones may activate not only cell bodies but
      also neuronal fibres, this study aimed to test a selectively cholinergic
      neurochemical stimulation of the rat substantia innominata (SI) by the local
      microinjection of carbachol; the effects of this acetylcholine agonist were
      compared with glutamate. Cortical and subcortical cerebral blood flow (CBF) were
      measured in anaesthetized rats with the [14C]iodoantipyrine method by the tissue
      sampling technique immediately following the intracerebral (SI) microinjection of
      saline, 50 nmol of carbachol or glutamate. Carbachol microinjection into the SI
      induced a transient but significant vasodilation in frontoparietal motor (+28%)
      and temporal (+41%) cortices, that lasted for less than 10 min. Glutamate did not
      elicit any significant CBF modifications when compared to control rats although a
      significant interhemispheric asymmetry after microinjection was observed in the
      frontoparietal motor cortex. This latter observation would suggest that the
      glutamate-induced cortical response is less pronounced than that elicited by
      carbachol. Overall, these results demonstrate that a selective cholinergic
      stimulation of the SI can induce a transient cortical vasodilation and further
      confirms the hypothesis of a muscarinic modulation of CBF via this basal
      structure.

PMID- 7644126
TI  - Involvement of the Y2 receptor subtype in the regulation of prolactin gene
      expression by neuropeptide Y in the male rat.
AB  - In order to determine the influence of neuropeptide Y (NPY) on the biosynthesis
      of prolactin (PRL), we have studied the effects of NPY and some NPY analogs on
      PRL gene expression in the male rat anterior pituitary gland. The following
      peptides (4 micrograms/100 g body wt): NPY, peptide YY (PYY), NPY13-36 (a Y2
      receptor agonist) and [Leu31,Pro34]NPY (a Y1 receptor agonist) were injected into
      the left lateral ventricle of adult male rats. Control animals received only the
      vehicle (0.9% NaCl). All the animals were perfused with 4% paraformaldehyde 4 h
      after injection and processed for in situ hybridization. The
      intracerebroventricular injection of NPY, PYY, and NPY13-36 induced a significant
      increase in the hybridization signal (22-40% over control). On the other hand,
      the Y1 receptor agonist [Leu31,Pro34]NPY did not influence PRL mRNA levels. These
      data then suggest that activation of the Y2 NPY receptor subtype at the central
      level can positively regulate PRL gene expression.

PMID- 7644128
TI  - Endothelins stimulate sodium uptake into rat brain capillary endothelial cells
      through endothelin A-like receptors.
AB  - The effect of endothelins (ETs) on sodium/hydrogen (Na+/H+) antiport system was
      examined in cultured rat brain capillary endothelium (RBEC). ET-1, ET-2, and ET-3
      stimulated Na+ uptake into RBEC with similar half-maximal stimulation (EC50)
      values (0.7, 0.6, and 1.1 nM, respectively). This reaction was inhibited by the
      Na+/H+ antiport inhibitor, N-(ethyl-N-isopropyl)-amiloride (EIPA). The selective
      endothelin A (ETA) receptor-antagonist (cyclo-D-Trp-D-Asp-Pro-D-Val-Leu (BQ123)),
      but not endothelin B (ETB) receptor-antagonists ((Cys11, Cys15)-ET-1 (IRL1038) or
      N-cis-2,6-dimethylpiperidinocarbonyl-L-gamma MeLeu-D-Trp(COOMe)-D-Nle-ONa
      (BQ788)), inhibited both ET-1- and ET-3-stimulated Na+ uptake, indicating ETA
      receptor mediation. The protein kinase C (PKC) activator (phorbol 12-myristate 13
      acetate (PMA)) failed to stimulate Na+ uptake. The calcium-calmodulin (CaM)
      inhibitor (W7) reduced ET-1-stimulated Na+ uptake by 50%, whereas the PKC
      inhibitor (staurosporine) had no effect, indicating that ET-1 stimulation of the
      Na+/H+ antiport system is linked to a CaM-dependent and PKC-independent pathway.

PMID- 7644129
TI  - ATP-evoked potassium currents in rat striatal neurons are mediated by a P2
      purinergic receptor.
AB  - The effect of ATP on cultured striatal neurons was examined by whole cell voltage
      clamp recordings. ATP produced outwardly rectifying currents that reversed near
      the expected equilibrium potential for the potassium ion and the currents were
      blocked by intracellular Cs+. Purinergic receptor agonists such as ADP, AMP
      adenosine, and 2-methylthio ATP (2-MeSATP) also evoked similar outward currents.
      The order of their potencies was ATP >> 2-MeSATP > or = ADP > adenosine > AMP,
      corresponding to a P2 purinergic receptor. ATP-evoked currents were blocked by a
      specific protein kinase C (PKC) inhibitor, GF109203X. In addition, the
      intracellular perfusion of a G-protein inactivator, GDP beta S abolished ATP
      induced currents, whereas pertussis toxin (PTX) had no effect on the currents.
      These results suggest that ATP activates a potassium channel in striatal neurons,
      which is regulated by protein kinase C (PKC) activation through a P2 purinergic
      receptor linked to PTX-insensitive G protein.

PMID- 7644130
TI  - Field potential change in the prefrontal cortex of the left hemisphere during
      learning processes of reaction time hand movement with complex tone in the
      monkey.
AB  - Field potentials were recorded with electrodes implanted in various cortical
      areas while a naive monkey was learning reaction time hand movements with complex
      tone. When cortical surface-negative, depth-positive potential (at a latency of
      about 80 ms after a stimulus onset) appeared in the rostral bank of the inferior
      limb of the arcuate sulcus of the left cerebral hemisphere, and became gradually
      larger, the monkey began to respond to the stimulus with the movement. As the
      potential in the prefrontal (prearcuate) cortex and the cerebellar-mediated
      potential in the motor cortex gradually increased with further training, the
      movement became quicker and more skillful. Three naive monkeys achieved the
      movement with complex tone in shorter training days than the movement with pure
      tone; the movement with pure tone was not accompanied by any significant
      potential in the prefrontal cortex. It is deduced from the present study, and
      previous studies on visuo-initiated movements, that the prefrontal area,
      especially in the left hemisphere, plays a significant role for a monkey to
      associate a stimulus with appropriate motor execution.

PMID- 7644131
TI  - Effects of fetal brain grafting on adult behavioral masculinization and
      defeminization in neonatally androgenized female rats.
AB  - Treatment of neonatal female rats with androgen results not only in decreased
      female sexual behavior but also in enhanced male sexual behavior examined in
      adulthood. The effects of grafting fetal preoptic area (POA) neurons into the
      POA, and fetal hypothalamic (HPT) neurons into the ventromedial hypothalamus
      (VMH), were tested in neonatally androgen-sterilized rats (ASR). The rats were
      injected subcutaneously with 80 micrograms testosterone propionate within the 24
      hours after birth to see if sexual behavior could be normalized by fetal brain
      grafts. In repeated tests on ASR grafted with fetal HPT into the VMH, the
      lordotic response was seen to increase to the level seen in non-ASR controls,
      while the increase in mounting behavior in ASR was suppressed following grafting
      of fetal POA or cerebral cortex into the POA. These results suggest that there
      are dysfunctions of POA and VMH in ASR, and that the dysfunctions revealed by
      sexual behavior can be overcome by fetal POA or HPT grafting.

PMID- 7644132
TI  - Transcription factor DNA binding activity in PC12 cells undergoing apoptosis
      after glucose deprivation.
AB  - Following hypoglycemic injury to rat pheochromocytoma PC12 cells, cells display
      nuclear chromatin condensation and nucleosome-sized DNA fragmentation.
      Electrophoretic mobility shift assays were used to characterize binding of
      nuclear proteins to consensus sequences for AP-1, nuclear factor kappa B (NF
      kappa B), and octamer family after glucose deprivation. While AP-1 DNA binding
      activity and NF kappa B DNA binding activity were transiently stimulated, DNA
      binding to the octamer motif decreased. These data suggest that changes in
      nuclear protein binding to specific consensus sequences are an early molecular
      event in hypoglycemic-ischemic injury-induced neuronal cell death.

PMID- 7644133
TI  - The association of apolipoprotein E polymorphism with memory: a population based
      study.
AB  - Several studies have shown an association between the apolipoprotein epsilon 4
      allele and Alzheimer's disease (AD). The allele epsilon 2 has been associated
      with survival and longevity. We wanted to examine whether the relationship
      between cognitive efficiency and apolipoprotein E polymorphism (APOE) exists in a
      random sample of 916 non-demented elderly subjects. Episodic memory was examined
      with the list learning test, and with immediate and delayed recall of the
      figures. Semantic memory was examined with the Category and Verbal Fluency Tests.
      Constructional abilities were examined by copying the figures. Attention
      functions were examined with Trail Making A and B tests. We found that subjects
      with APOE E2/2 and 2/3 phenotypes showed better learning ability than those
      subjects with the APOE E2/4, 3/4 or 4/4 phenotypes. Impaired memory was not
      related to the excess of cardiovascular diseases in the subjects with APOE E2/4,
      3/4, 4/4 phenotypes. Thus they may be associated, at least partly, with genetic
      factors.

PMID- 7644134
TI  - The cardiac glycoside ouabain potentiates excitotoxic injury of adult neurons in
      rat hippocampus.
AB  - We demonstrate that the enzyme family responsible for the restoration of the
      transmembrane cation balance, namely the sodium pump (Na+, K(+)-ATPase), plays a
      critical role in whether glutamate injures adult neurons in vivo. Partial
      inhibition of the sodium pump by the cardiac glycoside ouabain in young adult
      rats is not itself damaging. This treatment, however, markedly potentiates
      ordinarily subtoxic dosages of the glutamate analog kainic acid to produce limbic
      seizures and widespread neurodegeneration within the hippocampus in a pattern
      closely resembling that observed for human temporal lobe epilepsy.

PMID- 7644135
TI  - Prenatal cocaine alters later sensitivity to cocaine-induced seizures.
AB  - Rats that had been prenatally exposed to cocaine were tested later in life for
      their sensitivity to cocaine-kindled seizures and acute cocaine-induced seizures.
      When treated daily with cocaine, beginning at one month of age, males prenatally
      exposed to 40 mg/kg cocaine developed seizures in a fewer number of days than
      those prenatally exposed to saline. Prenatally cocaine-treated females did not
      seize more rapidly than controls in the cocaine kindling paradigm; however, they
      were more susceptible to seizures in response to an acute high dose of cocaine.
      These results suggest that rats prenatally cocaine-treated are more sensitive to
      the seizure-producing effects of cocaine later in life, and this enhanced
      sensitivity is differentially expressed in males and females.

PMID- 7644136
TI  - Acute action of ethanol on rat hippocampal CA1 neurons: effects on intracellular
      signaling.
AB  - Ethanol has a concentration dependent dual effect on electrical activity of rat
      CA1 hippocampal neurons. Low concentrations of ethanol (0.001%) enhance whereas
      high concentrations (0.5%) suppress synaptic transmission. Ethanol has no effect
      on cell input resistance and orthodromic or somatic threshold of action
      potentials. Cholera toxin, an activator of stimulatory guanine nucleotide binding
      regulatory protein (Gs), prevented the ethanol effects on field excitatory
      postsynaptic potentials (EPSPs). Staurosporine, an inhibitor of protein kinases,
      bisindolylmaleimide, an inhibitor of protein kinase C, and phorbol-12,13
      dibutyrate (PDBu), an activator of protein kinase C, blocked the effect of
      ethanol on field EPSPs. Our results show that ethanol at extremely low
      concentrations is able to affect synaptic transmission and suggest that the
      molecular mechanism of ethanol action involves the activation of Gs protein and
      protein kinase C.

PMID- 7644137
TI  - Neurons of the olfactory organ projecting to the caudal telencephalon and
      hypothalamus: a carbocyanine-dye labelling study in the brown trout (Teleostei).
AB  - The caudal extrabulbar projections and their neurons of origin in the trout were
      studied after carbocyanine-dye (DiI) labelling in either the olfactory organ or
      the caudal telencephalon. DiI application to the caudal telencephalon labelled
      bipolar neurons in the olfactory epithelium, where they were sparsely distributed
      throughout the olfactory lamellae. Labelled fibres ran scattered in the olfactory
      nerve without forming bundles. DiI application to the olfactory organ labelled
      extrabulbar projections to the ventral telencephalon, preoptic region and tuberal
      hypothalamus. These results confirm that primary sensory fibres running in the
      medial olfactory tract of trout have an olfactory origin.

PMID- 7644138
TI  - Ultradian rhythm in the delta and theta frequency bands of the EEG in the
      posterior hypothalamus of the rat.
AB  - The EEG signal of the area hypothalami posterior (PH) was recorded in the
      urethane anaesthetized rat. The main characteristic of the EEG in this brain
      region was intermittent oscillations of high amplitude in the delta and theta
      frequency bands. Oscillations of the alpha and beta frequency bands showed
      comparatively lower variations. Time distribution analysis of the EEG spectral
      power revealed that the delta and theta rhythms appeared and disappeared
      according to an ultradian rhythm with a frequency of approximately 1 cycle per
      100 min. No significant rhythm was found in the alpha and beta band. The rhythm
      frequency of neuronal activity in the PH is very similar to the ultradian
      frequency of pulsatile neurotransmitter release in the PH demonstrated
      previously.

PMID- 7644140
TI  - Programmed cell death of PC12 induced by adenovirus E1A.
AB  - PC12 rat pheochromocytoma cells undergo programmed cell death or apoptosis with
      DNA fragmentation when deprived of serum. Here, we isolated a subclone of PC12,
      PC12FrR, that was resistant to DNA fragmentation in a serum-free condition.
      PC12FrR grew slightly faster, and had cells that were slightly larger than
      parental PC12 cells. Adenovirus E1A gene-transfected PC12FrR cells grew much
      faster than did parental PC12FrR cells in the presence of serum. In a serum
      deprived condition, E1A-transfected PC12FrR cells died with DNA fragmentation, as
      did PC12 cells under the same conditions. These results suggest that the
      target(s) of E1A gene products may be involved in the mechanism(s) that regulate
      growth and death of neuronal cells.

PMID- 7644139
TI  - Effect of MK-801 and U83836E on a porcine brain capillary endothelial cell
      barrier during hypoxia.
AB  - The present study investigated the influence of MK-801 (N-methyl-D-aspartate
      receptor antagonist) and U83836E (antioxidative aminosteroid) on the permeability
      of sodium fluorescein through a cell barrier during hypoxia (2 h 95% N2/5% CO2).
      The barrier consisted of porcine brain capillary endothelial cells and of
      cerebral rat astrocytes cultivated on two sides of a filter. After hypoxia, the
      permeation of fluorescein was significantly increased (10.2 +/- 1.5 x 10(-3)
      cm/min, P < 0.001) compared to the normoxic control (2 h 95% O2/5% CO2, 1.8 +/-
      0.6 x 10(-3) cm/min). The hypoxia-enhanced permeation was significantly (P <
      0.05) reduced by 10 microM MK-801 (2.0 +/- 0.5 x 10(-3) cm/min) and 10 microM
      U83836E (3.1 +/- 1.3 x 10(-3) cm/min). The results demonstrate, for the first
      time in a cell culture system, that hypoxia impairs brain endothelial barrier
      function, and that this enhanced permeability can be influenced
      pharmacologically. It is concluded that two distinct pathogenic mechanisms are
      involved in hypoxic cerebral endothelial cell injury, and that cerebroprotection
      afforded by these agents may result, in part, from reductions in edema secondary
      to improved blood-brain barrier function.

PMID- 7644141
TI  - NADPH-diaphorase activity in the sympathetic preganglionic neurons of the
      filefish, Stephanolepis cirrhifer.
AB  - Enzyme histochemistry combined with horseradish peroxidase retrograde tracing
      demonstrated NADPH-diaphorase activity in the spinal sympathetic preganglionic
      neurons in the spinal cord of the filefish, Stephanolepis cirrhifer, these
      neurons with NADPH-diaphorase activity were located just dorsal and lateral to
      the central canal. The results indicate that nitric oxide is synthesized in the
      spinal sympathetic preganglionic neurons of filefish.

PMID- 7644142
TI  - Characterisation of a functional E box motif in the proximal rat preprotachykinin
      A promoter.
AB  - Three E box motifs, which are upstream of the major transcriptional start site,
      have previously been characterised in the rat preprotachykinin-A (rPPT) promoter.
      Only one of these, in the proximal promoter spanning nucleotides -67 to -47, has
      been demonstrated to support reporter gene expression in clonal cell lines under
      basal growth conditions. Here we demonstrate that the reporter gene expression
      can be further induced by the action of phorbol 12-myristate 13-acetate (TPA) and
      nerve growth factor (NGF), respectively, in both HeLa and the neuronally derived
      PC12 cells. This response is due to the E box motif and not an overlapping
      consensus sequence for a putative AP1 element, a class of element previously
      demonstrated to respond to both TPA and NGF in these cell lines. Finally, we
      demonstrate that this E box motif can support similar levels of reporter gene
      expression in primary cultures of dorsal root ganglion neurons as observed in
      clonal cell lines, demonstrating that E box binding complexes can (1) function as
      a transcriptional regulator in dorsal root ganglion neurons and (2) bind to and
      therefore presumably regulate rPPT promoter activity.

PMID- 7644143
TI  - Ref-1 expression in adult mammalian neurons and astrocytes.
AB  - Ref-1 is a nuclear protein that possesses DNA repair activity and has a role in
      the redox activation of Fos and Jun transcription factors. Using an antibody to
      Ref-1 we investigated the expression and distribution of this protein in the
      adult rat brain. Ref-1 was located in the nucleus of neurons and glial fibrillary
      acidic protein-positive astrocytes throughout the brain. Levels were particularly
      high in granule cells of the dentate gyrus, piriform cortex neurons, and Purkinje
      cells of the cerebellum, and lower in CA1 pyramidal cells, striatal neurons, and
      the neurons of the neocortex. These results suggest that the action of inducible
      transcription factors such as c-Jun in mammalian neurons is likely to be
      regulated by constitutively expressed Ref-1, in particular in dentate granule
      cells. The high levels of Ref-1 in glial fibrillary acidic protein-positive
      astrocytes suggest that it may also modulate the action of inducible
      transcription factors in these cells, particularly after brain injury. The
      possibility also exists that Ref-1 may primarily function as a DNA repair enzyme
      in brain cells.

PMID- 7644144
TI  - A novel gamma-aminobutyric acid response in the embryonic brainstem as revealed
      by voltage-sensitive dye recording.
AB  - Using a multiple-site optical recording technique employing a fast voltage
      sensitive dye, we found a novel type of gamma-aminobutyric acid (GABA) response,
      which is insensitive to GABAA and GABAB antagonists, but is stimulated by either
      GABAA or GABAB agonist. This evidence was identified in the early embryonic
      brainstem slice preparation.

PMID- 7644145
TI  - Up-regulation of cholecystokinin receptors in the nucleus accumbens of the young
      prehypertensive spontaneously hypertensive rat.
AB  - We employed receptor autoradiography to test the hypothesis that changes in
      cholecystokinin neurotransmission in the striatum of the young spontaneously
      hypertensive rat (SHR) is involved in the development of hypertension. The
      binding density of 125I-Bolton Hunter labelled cholecystokinin octapeptide (125I
      BH-CCK8) in the striatum of 5-week-old prehypertensive SHRs and its normotensive
      control the Wistar-Kyoto rat (WKY) was determined using computer-assisted
      densitometry. We found a significant increase in 125I-BH-CCK8 binding density in
      the nucleus accumbens of the SHR. No difference between the binding density of
      125I-BH-CCK8 was found in the caudate-putamen and the prefrontal cortex of SHRs
      and WKYs. These results suggest that changes in CCK8S neurotransmission or
      receptor function are not secondary to an increase in arterial blood pressure
      and, therefore, may be involved in the development of hypertension.

PMID- 7644146
TI  - Regulation of stimulus-dependent hippocampal acetylcholine release by okadaic
      acid-sensitive phosphoprotein phosphatases.
AB  - Isolated nerve endings (synaptosomes) from rat hippocampus were used to
      characterize the influence by serine/threonine-specific phosphoprotein
      phosphatase (PP) inhibitors on acetylcholine release. Brief exposure to low
      concentrations of selective PP inhibitors (okadaic acid and calyculin A) caused a
      concentration-dependent attenuation of stimulus-dependent (calcium-evoked or
      potassium-evoked) [3H]acetylcholine ([3H]ACh) release, while having no effect on
      the rate of basal transmitter efflux. In view of the observed potencies for
      okadaic acid and calyculin A (pseudo-IC50 values near 3 nM), these data indicate
      that Type 1 (PP1) or Type 2A (PP2A) enzymes play a permissive role in exocytotic
      [3H]ACh release. In contrast, the absence of any measurable effect by sodium
      orthovanadate argues against a similar influence by tyrosine-specific
      phosphoprotein phosphatases. While the neuronal substrate(s) responsible for PP
      regulation of [3H]ACh release are unknown, the underlying mechanism clearly
      differs from that through which muscarinic autoreceptors act since inhibition by
      okadaic acid and oxotremorine (an autoreceptor agonist) are additive and the
      former is not blocked by the muscarinic receptor antagonist atropine. Based upon
      these results, we conclude that dephosphorylation steps catalyzed by okadaic acid
      sensitive PP represent an important regulatory mechanism for stimulus-dependent
      transmitter release in septo-hippocampal cholinergic neurons.

PMID- 7644147
TI  - Group Ia non-reciprocal inhibition from wrist extensor to flexor motoneurones in
      humans.
AB  - Interneurones mediating disynaptic inhibition from extensor to flexor carpi
      radialis muscles were characterized by pharmacological stimulation of Renshaw
      cells. It is, indeed, known that only Ia interneurones are blocked by recurrent
      inhibition. Renshaw cell potentiation, induced by intravenous administration of 2
      g levo-acetylcarnitine, blocked Ia reciprocal inhibition from triceps to biceps
      muscles but not disynaptic inhibition from extensor to flexor carpi radialis
      muscles. It is concluded that the interneurones mediating this latter inhibition
      are not Ia interneurones. This kind of inhibition could be an example of a Ia non
      reciprocal inhibitory pathway.

PMID- 7644149
TI  - Aging and lymphokine gene expression by T cell subsets.

PMID- 7644148
TI  - Criteria for determining recommended dietary allowances for healthy older adults.

PMID- 7644150
TI  - Patterns of age-related immunologic changes.

PMID- 7644151
TI  - Immune senescence: deficiency or dysregulation.

PMID- 7644152
TI  - Mechanisms underlying the increased susceptibility of aged mice to tuberculosis.

PMID- 7644153
TI  - Decreased immunity and increased morbidity in the elderly.

PMID- 7644154
TI  - Interpretation of animal and human intervention trials.

PMID- 7644155
TI  - Vitamin E enhancement of T cell-mediated function in healthy elderly: mechanisms
      of action.

PMID- 7644156
TI  - Studies on micronutrient supplements and immunity in older people.

PMID- 7644157
TI  - Immunogerontologic outcomes of dietary restriction started in adulthood.

PMID- 7644158
TI  - Effects of calorie restriction and omega-3 fatty acids on autoimmunity and aging.

PMID- 7644159
TI  - Cellular and biochemical changes in the aging mouse immune system.

PMID- 7644160
TI  - Nutrition and immunity in the elderly: clinical significance.

PMID- 7644161
TI  - Protein undernutrition as the major cause of decreased immune function in the
      elderly: clinical and functional implications.

PMID- 7644162
TI  - Immunologic roles of two metabolic hormones, growth hormone and insulin-like
      growth factor-I, in aged animals.

PMID- 7644163
TI  - Textbook case. Don't go by the book.

PMID- 7644164
TI  - Botulinum toxin; one man's poison is another man's potion.

PMID- 7644165
TI  - Growth patterns and outcomes in congenital adrenal hyperplasia; effect of chronic
      treatment regimens.
AB  - AIM: To assess outcome (final height and sexual maturation), growth patterns and
      blood pressure in 16 children with congenital adrenal hyperplasia treated at one
      institution over a 30 year period. METHODS: Growth patterns and maturation were
      determined by retrospective review (median follow up period 14 years). Dose
      adjustment of corticosteroid replacement treatment, sufficient to maintain normal
      levels of adrenal precursor secretion, was determined using assays of urinary
      pregnanetriol excretion (up to 1975) or early morning measurements of plasma 17
      hydroxy progesterone and plasma renin activity at intervals of 4-6 months.
      RESULTS: In 7 of 15 patients the growth pattern during infancy was retarded--13
      not exceeding the population mean. Catchup growth as steroid dose fell with age
      was not usually observed. In boys, height potential was further compromised by a
      significant reduction in growth velocity during puberty. None of nine patients
      evaluated at final height had attained the target height. During the first year
      of life, plasma renin activity was suppressed below the reference range in six of
      nine infants. Despite this, and lower than normal levels of plasma renin activity
      in childhood, most children were normotensive. CONCLUSIONS: Avoiding salt
      depletion in infancy and excessive androgen secretion during childhood do not
      ensure normal growth patterns or normal final height. Impaired final height in
      congenital adrenal hyperplasia is more likely to be due to over treatment,
      particularly in infancy when lower doses of corticosteroids may improve height
      prognosis.

PMID- 7644166
TI  - Telephone advice about an infant given by after-hours clinics and emergency
      departments.
AB  - AIMS: Studies have shown that telephone calls for advice constitute a significant
      portion of the workload of emergency departments in the United States and the
      United Kingdom. Reviews of the appropriateness of telephone advice given in
      emergency departments in the United States indicate that the information given is
      often inadequate or inaccurate. We performed a study to evaluate the telephone
      advice given in New Zealand. METHODS: We identified 30 public hospital emergency
      departments and 20 private accident and emergency clinics. Twenty-six towns and
      cities were represented. We telephoned each of them and requested advice about
      the management of a fictitious febrile infant. RESULTS: We were given medical
      advice by 36 of the centres. In the remaining 14 the caller was referred to an
      oncall duty doctor or general practitioner for further information. In the 36
      departments providing advice, the information was given by a doctor in 5 of the
      cases, by a nurse in 26, and by a receptionist or unidentified respondent in 5.
      On average, the caller was asked 3.76 questions about the patient before advice
      was given. Even if a number of questions were asked, correct advice did not
      necessarily follow. Thirty five of the advice givers requested the age of the
      infant, but 16 of them gave inadequate advice despite this knowledge. We judged
      the advice given to be inadequate in 16 of the 36 institutions that provided it.
      There was no difference in the standard of advice given by private and public
      institutions. DISCUSSION: This study demonstrates that there are deficiencies in
      the quality of telephone advice given by emergency departments and private
      accident and emergency clinics in New Zealand.

PMID- 7644167
TI  - Assessment of the risk of transmission of N meningitidis in a classroom setting.
AB  - AIM: To evaluate the risk of colonisation with N meningitidis among university
      classroom contacts of a student with invasive meningococcal disease. METHODS:
      Throat cultures were obtained from classmates and faculty exposed to a university
      student with meningococcal disease. Exposures to the index case were quantified
      using a questionnaire. RESULTS: None of the 41 students and staff from whom
      cultures were obtained showed evidence of colonisation with N meningitidis. The
      contacts had spent an average of 13.5 h in class with the index case during the 2
      days prior to the onset of her illness. CONCLUSIONS: The risk of colonisation
      with N meningitidis among casual university classroom contacts appears to be low.
      This study lends support to decisions to withhold chemoprophylaxis in most
      instances of such contact.

PMID- 7644168
TI  - A direct threat to research in public hospitals.

PMID- 7644169
TI  - Bedsharing and cot death.

PMID- 7644170
TI  - Sceptical of sceptics.

PMID- 7644171
TI  - Sound solutions for industrial noise.

PMID- 7644172
TI  - Special product focus: Vision protection.

PMID- 7644173
TI  - Throw away your old safety forms.

PMID- 7644174
TI  - Cutting nursing care hurts patients.

PMID- 7644177
TI  - Please give further guidance on the RN's responsibility in delegating tasks to
      the LPN.

PMID- 7644178
TI  - Alternatives.

PMID- 7644176
TI  - Fighting institutional licensure.

PMID- 7644175
TI  - Drug therapy in older adults: effects of altered pharmacokinetics and
      pharmacodynamics (continuing education credit).

PMID- 7644179
TI  - Educating your legislators.

PMID- 7644180
TI  - Library services for Oklahoma nurses.

PMID- 7644181
TI  - How's your ethics???

PMID- 7644182
TI  - Prescriptive authority for advanced practice nurses in Oklahoma.

PMID- 7644183
TI  - Insightful, innovative, and intuitive: a Nominating committee for the new ONA.

PMID- 7644184
TI  - Malnutrition risk factors in elderly persons.

PMID- 7644186
TI  - [Diagnosis and differential diagnosis of psoriatic arthritis on basis of follow
      up of 215 cases].
AB  - The interval between the appearance of the symptoms of psoriasis and/or arthritis
      and the setting up the diagnosis of the psoriatic arthritis was studied in 215
      patients suffering from definite psoriatic arthritis. About 2.3 years were over
      until the setting-up of the diagnosis in these 30 patients whose psoriasis and
      arthritis began simultaneously. The interval to set up the diagnosis of psoriatic
      arthritis was 5.4 years in average if the psoriasis itself was the first sign and
      it was 8.6 years in case the arthritis preceded psoriasis. The symptoms promoting
      to set up the right diagnosis were in order to frequency as follows: appearance
      of psoriasis, sausage digits, distal interphalangeal involvements, nail changes
      and transformation the monoarthritis into asymmetrical oligoarticular or
      polyarticular form. The difficulty of the differential diagnosis was studied. 15
      different previous false diagnoses were enumerated the rate of which was the
      highest (67.3%) in the group starting with arthritis. The authors call the
      attention to the importance of looking for psoriatic skin and nail changes in
      every nonclassified arthritic patient in the interest of an early diagnosis and
      right therapy in course of the follow-up.

PMID- 7644185
TI  - Peptide chain elongation: a possible role of montmorillonite in prebiotic
      synthesis of protein precursors.
AB  - Several studies have proven the ability of montmorillonite to catalyse amino acid
      condensation under assumed prebiotic conditions, simulating wetting-drying
      cycles. In this work, the oligomerization of short peptides gly2, gly3, gly4 and
      ala2 on Ca- and Cu-montmorillonite in drying-wetting cycles at 80 degrees C was
      studied. The catalytic effect of montmorillonite was found to be much higher than
      in the case of glycine oligomerization. From gly2 after 3 weeks, 10% oligomers
      (up to gly6, with gly3 as main products) are formed. Gly3 and gly4 give higher
      oligomers even after 1 cycle. Ala2 produces both ala3 and ala4, whereas ala does
      not produce any oligomers under these conditions. Heteroologomerization was
      observed: ala-gly-gly is formed from ala and gly2. Much higher yields are
      obtained using Ca-montmorillonite, because copper (II) oxidizes organic
      molecules. The influence of the reaction mechanism on the preferential
      oligomerization of oligopeptides is discussed.

PMID- 7644187
TI  - [Clinical and biochemical parameters of patients with vascular stenosis in the
      lower extremities in the stage of intermittent claudication].
AB  - Clinical and biochemical parameters obtained by complex investigation of 100
      patients suffering from intermittent claudication are presented by the authors.
      After taking the family and case history, we examined the patients and took
      laboratory tests including several lipid components, blood clotting factors and
      parameters influencing blood viscosity. The severity of peripheral vascular
      disease was defined by ankle/arm ratio, carotid arteries were studied by duplex
      sonography, coronary circulation was examined by ECG, exercise ECG and Thallium
      201 isotopic myocardium scintigraphy. In conjunction with lower extremity
      vascular disease internal carotid stenosis was diagnosed in 62% and coronary
      stenosis in 52% of cases examined. In 35% all three regions were affected. The
      degree of carotid stenosis showed a strong correlation to the severity of the
      claudication, while in case of the coronary disease there was no connection
      proved, in spite of its high prevalence. Among the risk factors smoking was
      present in 89%, hypercholesterolaemia in 84%, hypertension in 54%, diabetes
      mellitus in 13%, impaired glucose tolerance in 42% and positive family history in
      39% of cases. Smoking and accumulation of the risk factors showed correlation to
      the severity of the lower extremity vessel stenosis, while hypertension and
      carbohydrate metabolism disturbances showed significant correlations to the
      degree of carotid stenosis. From different lipid parameters only the
      cholesterol/HDL-cholesterol ratio showed significant correlation to the severity
      of the arteriosclerosis. The authors refer to intermittent claudication as the
      risk factor for carotid and coronary disease. They suggest the assessment of the
      cerebrovascular and cardiac risk in the patients. This way the optimal order of
      operative and/or non-operative therapy can be realized.

PMID- 7644188
TI  - [Immune thrombocytopenic purpura and pregnancy: maternal risk factors].
AB  - Authors analyse 75 pregnancies and 51 deliveries, respectively, of 45 mothers
      with chronic immune thrombocytopenia (ITP) from the point of view of maternal
      risks. Pregnancies that occurred in active disease were electively terminated. It
      was found that pregnancy contributed to the clinical manifestation of ITP, and
      antepartal bleeding took place in 18%, and preeclampsia emerged in 6%. The
      chronic ITP showed exacerbation during pregnancy in 27.3%, thus causing
      antepartal bleeding in 4.5% and postpartal bleeding in 15.9%. Postpartal bleeding
      presented in total 20%, not only in cases with severe ITP, but also in moderate
      ones. Postpartal blood transfusion was needed in 16%. The postpartal reduction of
      hemoglobin level determined 2-3 days following delivery was higher than in those
      ITP patients who had no postpartal haemorrhage than that in the general
      obstetrical population. This suggests an increased blood loss associated with
      delivery in patients with ITP. Maternal morbidity of patients with ITP in whom
      the disease first manifested during pregnancy was higher than that of those
      patients in whom pregnancy was associated with the remission of ITP. In order to
      decrease the maternal risks in ITP we advise that pregnancy should occur and be
      carried during remission.

PMID- 7644189
TI  - [Tilt-table test in the diagnosis of syncope of unknown origin].
AB  - 71 patients with unexplained syncope was examined by 60 grade of head up tilt
      table test with or without administration of isoproterenol during 25 minutes
      interval. The mean age of patients was 71.44 +/- 16.40 (12-86) years. 38 (54%)
      were female and 33 (46%) were male. The underlying heart disease were 27 (38%)
      coronary artery disease, 12 (17%) arterial hypertension, 6 (8%) diabetes
      mellitus, 3 (4%) valvular heart disease and 14 (20%) patients had other diseases.
      Nine (13%) patients had no organic disease. During head up tilt table test
      positive reaction was found in 13 (18%) patients. Four (6%) patients were vaso
      vagal syncope with classic signs, and 9 (13%) patients were vasodepressor type of
      syncope, without changes in the heart rate. Isoproterenol was given to 16 (23%)
      patients, and in 4 (6%) (2 vasodepressor and 2 mixed type of syncope) patients
      occurred the positive test during isoproterenol administration. Orthostatic
      reaction occurred during head up tilt table test in 14 (20%) patients. Normal was
      the result of tilt table test in 42 (59%) patients, and two (3%) patients had
      autonome neuropathy. The vasovagal syncope was treated by metoprolol, atenolol
      and disopyramid with success. The head up tilt table testing is a good, simple,
      useful test for evaluation of syncope patients, especially the diagnosis of
      vasovagal syndrome.

PMID- 7644190
TI  - [Benign recurrent intrahepatic cholestasis].
AB  - The authors report the medical history of a 19-year-old male patient, who had
      been admitted to the department of infectious diseases three times with recurrent
      icterus of unknown origin, suspected of viral hepatitis before his internal
      examination. The clinical picture and the histological results of liver biopsy
      performed in acute phase proved the presence of a rare hyperbilirubinaemia
      syndrome, "the syndrome of benign recurrent, intrahepatic cholestasis". The
      authors briefly describe Summerskill-Walshe syndrome and its place in different
      hyperbilirubinaemia disorders.

PMID- 7644191
TI  - [Responsibility of physicians treating cancer patients. Scientific Committee of
      Public Health].

PMID- 7644192
TI  - [In memory of Lajos Szodoray (1904-1980)].

PMID- 7644193
TI  - [Lajos Aranyi in the War of Independence].

PMID- 7644194
TI  - [Swallowing disorders in patients after the laryngeal cancer surgery].
AB  - Anatomical and functional changes of the oral cavity, pharynx and larynx due to
      malignant tumor surgery and irradiation, cause breathing, swallowing, phonation
      and lung protection disorders. Deglutition disorders and choking are observed in
      all patients who have undergone supracricoid laryngectomy. We presented 33
      patients after supracricoid laryngectomy with simultaneous CHEP (6) or CHP (27)
      reconstructions. 18 patients had one arytenoid cartilage removed, in 1 patient
      both of them were removed. Removal of the stomach tube took place between 29-36th
      day after the surgery. 4 patients showed symptoms of the aspiration pneumonia.
      Difficulties in swallowing liquids persist in some cases even a few years after
      the surgery. Re-education and rehabilitation of swallowing is the predominant
      problem and the most important goal after the CHP and CHEP surgery.

PMID- 7644195
TI  - [Voice and spirometric examinations in patients after laser arytenoidectomy].
AB  - Spirometric, phoniatric and acoustic investigations were performed in 13 patients
      after laser arytenoidectomy due to bilateral vocal cord paresis. Phoniatric
      examination included voice recording, average level and voice range, time of
      phonation, laryngoscopy and stroboscopy. Acoustic analysis covered harmonic
      structure of the voice, jitter, shimmer, noise component, basic frequency.

PMID- 7644197
TI  - [The development of the laryngeal cancer surgery].
AB  - We present historical review after treatment of laryngeal cancer. Complications
      after partial and total operations of laryngeal cancer was presented. Their
      results and complications were development of surgical treatment of laryngeal
      cancer.

PMID- 7644196
TI  - [Voice and spirometric function i patients after expanded fronto-lateral
      laryngectomy by using the Szmeja method].
AB  - The examination was carried out on 32 patients with larynx cancer, before and
      after fronto-lateral laryngectomy with reconstruction, using cartilage-mucous
      membrane transplant from the nasal septum. Before and after the surgery the
      following examinations were carried out: 1. phoniatric evaluation of voice, 2.
      acoustic analyses of voice, 3. spirometric examination. The phoniatric
      examination included evaluation of voice characteristics, time of phonation,
      anatomic mechanism of voice creation and evaluation of voice tiredness with the
      use of stroboscopy. Acoustic examination included the frequency evaluation of
      laryngeal sound and its range, jitter shimmer evaluation, harmonic structure of
      sound and the level of noise. The result obtained allow us to consider the voice
      and respiratory function as satisfactory.

PMID- 7644198
TI  - [Vestibulo-spinal and vestibulo-ocular reflexes in athletes].
AB  - There have been done tests of vestibulo-spinal et vestibulo- ocular reflexes at
      record-seeking sportsmen. At 141 sportsmen the vestibulo-spinal reflexes were
      tested by Unterberger-Fukuda stepping test in modification of Zilstorff-Pedersen
      and Peitersen. The angle of rotation (a), the distance of translocating to front
      or back (b) and the distance of sideward translocation (c) were estimated. The
      test was also done at 194 persons not playing sport. Comparing the average
      results of both groups the conclusion was drawn that sportsmen are characterized
      by lesser translocation of body within the range of all parameters of test, and
      differences of average are statistically substantial at the level of trust p = 0,
      001. The vestibulo- ocular reflexes were tested at 62 sportsmen by caloric test
      by method of Fitzgerald-Hallpike with electronystagmographic registering of
      nystagmus. The control group consisted of 30 persons not playing sport. The
      following features of nystagmus were estimated: duration time, maximum frequency,
      maximum amplitude and maximum angular velocity of the slow phase. The sportsmen
      were characterized by average lesser calorie excitability of labyrinth, although
      the differences between the tested groups were statistically substantial only
      within the range of some features of nystagmus.

PMID- 7644199
TI  - [The analysis of high frequency tympanograms according to Vanhuyse].
AB  - The high frequency tympanograms interpretation in theoretical consideration was
      the main subject of this study. The normal patterns of tympanograms 678 Hz was
      described. The most typical pathological tympanograms was presented. The special
      attention was paid on high frequency tympanometry diagnostic value in the
      ossicular chain pathology and the surgical treatment influence.

PMID- 7644200
TI  - [Evoked otoacoustic emissions in humans with normal hearing].
AB  - The aim of the study was to assess and compare click-evoked otoacoustic emissions
      (e-OAE) and distortion product otoacoustic emissions (DPOE) in normally hearing
      subjects. The study was conducted on 48 ears in adults (12 women and 12 men; the
      age ranging from 16 to 40 years). E-OAE and DPOE was present in all examined
      ears. The amplitude of e-OAE ranged from 3.4 to 23.5 dB SPL (mean 11.7 +/- 4.95
      dB SPL). In women the mean amplitude was slightly higher than in men. Spectral
      analysis of e-OAE revealed the highest level of otoacoustic emissions at the
      frequency 1000 Hz and significant decrease e-OAE at frequencies above 4500 Hz.
      DPOE were registered within the range of frequencies from 700 to 6000 Hz. Thus,
      DPOE allowed to measure otoacoustic emissions additionally in the high frequency
      region. We found significant variability in DPOE detection thresholds ranging
      from 25 to 70 dB SPL. Both types of otoacoustic emissions revealed significant
      inter-subject variability and very good test-retest repeatability. We conclude
      that both measurements allow to assess the function of the cochlea in the
      frequency specific regions, but DPOE, because of using pure tones stimuli, is
      more specific. The reference-values for adults are presented in this study.

PMID- 7644201
TI  - [Dominant symphalangism and conductive hearing loss].
AB  - Dominant symphalangism in three generations is presented in this paper.
      Conductive hearing loss of 14 year old male patient with proximal symphalangism
      was due to fixation of the stapes.

PMID- 7644202
TI  - [Chondrosarcoma of the paranasal sinuses and orbit].
AB  - A case of chondrosarcoma of paranasal sinuses and orbit penetrating to anterior
      cranial fossa is described. Treatment was surgical. Metastases and local
      recurrence after 7 month hasn't been reported.

PMID- 7644203
TI  - [The glossopharyngeal neuralgia with the coexisting cardiac rhythm disturbances].
AB  - We present the case of 61 years old man with idiopathic glossopharyngeal
      neuralgia. In the Holter's e.c.g often appeared the episodes of asystolia with
      the clinical symptoms of daze and confusion occurring during changing the
      position of the body (standing up). They were no accompanied by losses of
      consciousness. The patient was treated with carbamazepine during the cardiac
      disorders. The episodes of asystolia in e.c.g disappeared already 3 months after
      the end of the glossopharyngeal neuralgia.

PMID- 7644205
TI  - [A case of metastasis of the esophageal adenocarcinoma to the middle ear].
AB  - The authors have presented the rare case of metastasis the cardiac adenocarcinoma
      to the middle ear. They have described occurrence of metastatic tumors of the
      temporal bone, mechanisms of their formation, clinical picture, diagnostic
      difficulties, prognosis and ways of therapy. A radical surgical treatment and
      chemotherapy have been used in this case. The patient died 17 months after
      diagnosis of the cardiac adenocarcinoma and 10 months after diagnosis of
      metastasis to the temporal bone.

PMID- 7644204
TI  - [Thrombosis of the sigmoid sinus and transverse sinus with an unusual course].
AB  - A case of intracranial complication in patient with cephalgia and short period of
      the temperature without signs of sharpening chronic otitis is reported. At the
      time of the operation epidural abscess of fossa cranial posterior, perisinusal
      abscess and thrombus of sigmoid sinus, abscess in transverse sinus were found.

PMID- 7644206
TI  - [Glandular ear neoplasms].
AB  - A case of ceruminoma was described. The authors also presents actual opinions
      about glandular tumors of the middle and external ear, their classification and
      treatment.

PMID- 7644208
TI  - [A case of craniofacial trauma in a ten-year-old child].

PMID- 7644207
TI  - [Glioma of the ethmoid].
AB  - The authors presented a case of ethmoid glioma which had performed as nasal
      polyp. They also discussed about problems of classification and treatment this
      type of neoplasm.

PMID- 7644209
TI  - [Report from the 3rd international conference on pediatric otolaryngology.
      Jerusalem, November 7-12, 1993].

PMID- 7644210
TI  - [The surgical treatment of just one thyroid tissue on the tongue due to massive
      bleeding].
AB  - The authors present a rare case of lingual ectopic thyroid in 22 year--old-
      woman. A massive bleeding from the tumor occurred several times and required an
      urgent surgical treatment. A tracheostomy and ligation of the right external
      carotid artery were performed prior the removal of the tumor which was removed by
      medial pharyngotomy. No complications were observed. A substitutive hormonal
      therapy was administered. Six months after the tracheostomy tube was removed.

PMID- 7644211
TI  - [The suprahyoid approach for carcinoma of the base of the tongue].
AB  - From 1989 till 1993 10 patients with cancer of the base of the tongue were
      treated surgically. The surgical approach was suprahyoid pharyngotomy in 3 cases
      expand to intraoral approach and lateral pharyngotomy. Three patients died 3
      years after surgery. All patients underwent adjunctive irradiation. The
      suprahyoid pharyngotomy is an ideal surgical approach in the management of T1 or
      T2 squamous cell carcinoma of the base of the tongue.

PMID- 7644212
TI  - [The evaluation of the wound healing failure in patients after total
      laryngectomy].
AB  - The authors presented own results concerning complications in wound healing after
      total laryngectomies. 59 total laryngectomies and 4 pharyngo-laryngectomies were
      performed. In 18 cases local and systemic complications were observed. Pharyngo
      cutaneous fistulas developed in 15 patients. Therapeutic management was
      successful in all cases.

PMID- 7644213
TI  - [Difficulties in diagnosis of esophageal achalasia].
AB  - The authors present the case of 36 years old patient with dysphagia. This symptom
      appeared three years ago and became more severe for six month. The endoscopic and
      radiologic examinations revealed achalasia of the cardia. The surgical treatment
      was performed. Two weeks after surgery all symptoms disappeared. We present this
      case because achalasia of the cardia is comparatively rare disease which
      diagnostic is not easy.

PMID- 7644214
TI  - [Juvenile angiofibroma presented in the clinical materials of the
      Otolaryngological Department of the Academy of Medicine in Poznan in the years
      1977-1993].
AB  - 16 patients suffering from angiofibroma were treated in the Otolaryngological
      Clinic, Academy of Medicine in Poznan, in the years 1977--1993. The patients were
      aged from 10--36, the mean age 15. All patients were treated surgically, and the
      method choice was Denker's surgery. 3 patients were reoperated because of local
      relapse. On the bases of the described cases good results of full recovery of
      patients with angiofibroma treated surgically are presented.

PMID- 7644215
TI  - [CT examination of the temporal bones for cochlear implantation].
AB  - CT examinations of temporal bones were performed in 31 deaf patients from qualify
      diagnostic stage prepared for cochlear implants. Essential for surgical treatment
      anatomic details were estimated, especially canalis spiralis cochleae was paid to
      attention. In our group, 8 patients had some CT changes (abnormal findings) which
      corresponded to different stages of obliteration the cochlea. The majority of
      patients lost the hearing because of meningitis. In 6 implanted patients CT scan
      was compared with surgical findings. During the operation 1 patient with patent
      cochlea on CT scan had partially ossified basal turn.

PMID- 7644216
TI  - [The examination card for a child with suspected hearing loss or deafness].
AB  - An audiological examination card for a child has been worked out, allowing a
      detailed collection of anamnestic data concerning: family history, gestation,
      labour, neonatal period, infancy and early childhood. The items and possible
      answers contained in the card are so prepared that it can be used for computer
      analysis of the data obtained.

PMID- 7644217
TI  - [Sensorineural hearing loss in the course of acute otitis media].
AB  - The authors present two cases of acute otitis media complicated by perceptive
      hearing loss. According to the foreign publications they discuss reasons and ways
      of spreading the infections into the internal ear.

PMID- 7644218
TI  - [Experimental investigation of habituation transfer].
AB  - The subject of investigation was the possibility of the transfer of habituation.
      In 20 pigeons frequency of optokinetic and postrotatoric head nystagmus was
      established. Then in 10 birds optokinetic habituation training and in 10
      remaining pigeons rotatoric habituation training were performed. After
      acquisition of habituation in the first group, frequency of postrotatoric head
      nystagmus and in the second group frequency of optokinetic head nystagmus were
      defined. The transfer of optokinetic habituation to the rotatoric test was
      confirmed. The inverted process was not observed.

PMID- 7644220
TI  - [Meningioma of the orbit in a thirteen-year-old boy].
AB  - Primary meningioma of the orbit is very rare. A radical surgical treatment of
      primary meningioma of the orbit by a thirteen years old boy was carried out. Main
      symptoms communicated by the patient were amblyopia, which terminated in
      blindness, as well as increasing exophtalmos of a bulbus oculi. After the
      operation a regression of exophtalmos has been achieved while the blindness
      stayed unchanged.

PMID- 7644219
TI  - [Computer system of the electronystagmographic examination. Part III. Comparative
      results obtained by computer and traditional technology in the examination of the
      vestibular organ].
AB  - The study presents a comparison of the research into results of vestibular organ
      stimulated with caloric tests which had been simultaneously registered with the
      help of a computer system of electronystagmographic examination, as well as the
      traditional electronystagmographic technic. In the case of 32 healthy persons
      there had been counted by hand average angular velocity of the slow phase caloric
      nystagmus average level of reduced excitability of labyrinth and direction
      predominance. It had been defined that those values are comparable to the ones
      given by the computer. That points to the right chose of the space of time in the
      climax of nystagmus reaction and a good identification of the phase both slow and
      fast by the computer system.

PMID- 7644221
TI  - [Malignant fibrohistiocytoma of the larynx].
AB  - A patient in age 68 years with malignant fibrohistiocytoma of the larynx was
      surgically treated in the department of Otolaryngology, Medical University in
      Cracow. Fibrohistiocytoma is very rare tumor of the larynx. The diagnosis was
      supported by immunohistochemical examination. In the course of treatment were
      observed local relapses and neck metastases.

PMID- 7644222
TI  - [Dermoid cyst of the nose].
AB  - Dermoid cyst of the nose may present difficult management problems if
      inadequately evaluated preoperatively or if incompletely excited. The most
      important is to differentiate them from nasal gliomas, meningocoeles et
      encephalocoeles. The Otolaryngological Clinic of Jagiellonian University in
      Cracow presented a review of the congenital midline nasal mass during 1945 and
      1992 year. If a dermal fistule appears, it may be identified as a cutaneous
      defect leading from the midline of the nose. If this dermal fistule is connected
      with the skin of the nose it is called a dermal fistula dorsi nasi.

PMID- 7644223
TI  - [A case of aneurysmal cyst of the ethmoid sinus].
AB  - Aneurysmatic cyst occurs in the ethmoid sinus rarely. Basing upon the case of 5
      year old boy, the authors discuss the diagnosis, treatment and course of the
      disease.

PMID- 7644225
TI  - [Report from the VIth international congress of pediatric otolaryngology in
      Rotterdam in 1994].

PMID- 7644224
TI  - [Hearing disorders in children with Down's syndrome].

PMID- 7644226
TI  - [Scientific report on the 65th conference of the German Society of
      otolaryngologists, Chemnitz, May 14-18, 1994].

PMID- 7644227
TI  - Spend a day with a nurse.

PMID- 7644228
TI  - Mail vs. telephone--how should you initiate contact with your targeted employers?

PMID- 7644229
TI  - Human relations weaknesses--a leading cause of unsuccessful job campaigns.

PMID- 7644230
TI  - Conquering ADD.

PMID- 7644231
TI  - It's been 16 months. When the nurse is the patient.

PMID- 7644232
TI  - Differential treatment responses of TMD patients as a function of psychological
      characteristics.
AB  - A number of studies have reported that psychological factors play a significant
      role in TMD. Several studies have identified subgroups of patients based on their
      responses to psychological assessments; however, none of these studies have
      reported on the clinical utility of classifications of TMD patients on these
      various measures. In this study, the differential response of 133 TMD patients
      classified within 3 psychosocial-behaviorally based subgroups to a conservative,
      standardized treatment was examined. The treatment consisted of the combination
      of an intra-oral appliance, biofeedback, and stress management. Follow-up
      assessments were conducted 6 months after treatment termination. The results
      demonstrated that overall as a group patients significantly improved and
      maintained improvements on physical, psychosocial, and behavioral measures (P <
      0.0001). Comparisons across patient subgroups, however, revealed differential
      patterns of improvement on the outcome measures. Most notably, reliable change
      indices demonstrated that the patients classified into a subgroup characterized
      by the greatest degree of psychological distress (Dysfunctional) demonstrated
      significantly greater improvements on measures of pain intensity (P < 0.001),
      perceived impact of TMD symptoms on their lives (P < 0.001), depression (P <
      0.01), and negative thoughts (P < 0.001), compared with groups characterized by
      greater interpersonal problems (Interpersonally Distressed) and those patients
      who appeared to be the least disabled by TMD (Adaptive Copers). These data
      provide support for the clinical utility of a psychosocial-behavioral
      classification system and suggest that in future research individualizing
      treatments and outcome measures based on patient characteristics may improve
      treatment efficacy and outcome evaluation.

PMID- 7644233
TI  - Evidence for a peripheral origin of the tonic nociceptive response to
      subcutaneous formalin.
AB  - The orofacial formalin test in the rat is a valid and reliable model of
      nociception and is sensitive to various classes of analgesic drugs. The noxious
      stimulus consists in an injection of diluted formalin (2.5% in saline) into the
      upper lip. The behavioural nociceptive response is measured in terms of the
      amount of time the animal spends rubbing the injected area. Two distinct periods
      of intense rubbing activity can be identified, a first phase occurring in the
      first 3 min and a second phase lasting from 12 to 39 min after formalin
      injection. The present study verified the peripheral origin of the first phase of
      the formalin response and examined whether the second phase is produced by
      peripheral activation of afferent fibres and/or by a phenomenon of central
      facilitation induced by the neural activity that occurs during the first phase.
      This was determined by assessing the effect of a local anaesthetic agent
      (lidocaine) administered into the formalin injection site, before or after the
      first phase of the formalin response. Local injection of 50 microliters of
      lidocaine prior to formalin completely abolished the first phase of the formalin
      response but this blockade did not significantly influence the appearance and
      development of the second phase. Thus, the primary afferent activity that
      normally occurs during the first phase of the formalin response is not a
      prerequisite for the expression of the second phase. A higher dose of lidocaine
      (150 microliters) induced, in addition, inhibition of the first part of the
      second phase.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7644234
TI  - Myofascial face pain: seasonal variability in pain intensity and demoralization.
AB  - Seasonal variability has been detected in a variety of illnesses. The purpose of
      this study is to examine seasonal variability in pain intensity, demoralization
      and range of mandibular motion among patients suffering from myofascial face
      pain. Pain and demoralization for cases (n = 140) and demoralization for controls
      (n = 133) were measured in each of 10 monthly interviews. Range of motion was
      measured once only for cases. Their pain intensity (P < 0.009) and demoralization
      (P < 0.04) were significantly greater in the peak dark months than in the peak
      light months. There was a non-significant trend (P < 0.07) toward elevated
      demoralization in the darker months for controls. Range of motion, assessed cross
      sectionally, did not demonstrate a seasonal pattern. These data support our prior
      finding that myofascial face pain and depressed mood are co-morbid and may be
      maintained by common risk factors.

PMID- 7644235
TI  - Behavioral responses to uterine or vaginal distension in the rat.
AB  - Afferent fibers in the rat hypogastric and pelvic nerves supply the uterus and
      vagina, respectively, the former being responsive mainly to intense uterine
      stimuli, the latter to gentle and intense vaginal stimuli (Berkley et al. 1993c).
      If such responses result in sensory experiences, those produced by uterine and
      vaginal stimulation should differ, uterine stimuli being experienced mainly as
      pain and vaginal stimuli experienced in various ways, including pain. To test
      this hypothesis, 48 young virgin rats were first trained to make an operant
      response to escape a noxious tail-pinch stimulus. Latex balloons inserted into
      the rat's uterine horn or vagina were then distended to various volumes and the
      metestrous rat's detection behaviors and operant escape response probabilities
      measured. Approximately 26% of the 23 rats tested failed to respond to uterine
      stimulation, even when it produced ischemia. For the rest, detection and escape
      responses occurred only to ischemic stimuli and never to all of them, even at the
      highest volumes. In contrast, all 25 rats tested responded readily to vaginal
      distension, often to all of them at high volumes. Detection behaviors occurred at
      distension magnitudes lower than those that evoked escape responses. These
      results support the hypothesis that sensory consequences of uterine and vaginal
      stimulation differ. Because effective uterine stimuli were larger than any that
      would occur in a normal physiological state in non-pregnant/parturient rats,
      normally occurring uterine states in such rats are probably insensible. In
      addition, while the behavioral responses did indeed reflect differences in
      hypogastric and pelvic nerve response properties, the results also indicated that
      activity produced in those fibers, even by abnormal stimuli, does not inevitably
      result in behavior.

PMID- 7644236
TI  - The dominant class of somatosensory neurone recorded in the spinal dorsal horn of
      awake sheep has wide dynamic range properties.
AB  - In order to investigate the properties of dorsal horn neurones in the absence of
      the distorting influences of anaesthesia, preparative surgery, prior training or
      excessive restraint, recordings have been made in sheep chronically prepared for
      single-cell recording. Within the limitations of sampling error of dorsal horn
      neurones with cutaneous receptive fields, the cell type most frequently
      encountered had wide dynamic range (WDR; convergent; multireceptive) properties;
      these accounted for 59% of the 46 neurones that were examined in detail. High
      threshold mechanoreceptive (nocispecific) and low-threshold mechanoreceptive
      neurones formed 11% and 30% of the sample, respectively. These and other data
      indicate that under normal physiological conditions in the awake state, many
      spinal neurones do indeed have WDR properties, implying that these cells have an
      important function in nociceptive processing.

PMID- 7644237
TI  - Home management of sickle cell-related pain in children and adolescents: natural
      history and impact on school attendance.
AB  - Some children and adolescents with sickle cell disease experience frequent
      painful episodes. To gain information about the natural history of the pain and
      its impact on sleep and school attendance, we developed a home-based diary
      system. Eighteen children and adolescents completed 4756 diary days, with an
      average compliance of 75%. Pain was reported on 30% of days and was managed at
      home nine-tenths of the time. Girls reported more days with pain than did boys,
      and age was positively correlated with the length of the painful episodes. The
      pain affected school attendance and sleep. Patients were absent from school on
      21% of 3186 school days, with half of the absenteeisms on days with reported
      pain. Of the pain-associated absenteeisms, two-thirds occurred when pain was
      managed at home, and one-third when patients were hospitalized. The average
      consecutive number of school days missed was 2.7. These findings have
      implications for developmentally critical activities.

PMID- 7644238
TI  - Analgesic efficacy and safety of single-dose intramuscular ketorolac for
      postoperative pain management in children following tonsillectomy.
AB  - The efficacy of ketorolac, a non-steroidal anti-inflammatory drug, in the
      management of moderate to severe pain in adults, has led us to conduct a trial of
      this analgesic in children following tonsillectomy. Children were randomized to
      receive intramuscular (i.m.) ketorolac (1 mg/kg, EXP group, n = 45) or saline
      (CTL group, n = 42) at the completion of surgery. Intravenous (i.v.) fentanyl
      (0.5 micrograms/kg/dose) was administered in repeated doses postoperatively. Pain
      intensity was measured using both the Oucher and the Children's Hospital of
      Eastern Ontario Pain Scale (CHEOPS) to allow for comparison between self-report
      and behavioral measures of pain intensity. Severity of postoperative bleeding was
      measured using a 4-point rating scale. The EXP group had a significant reduction
      in total fentanyl dose (mean: 35.9 micrograms) compared to the CTL group (mean:
      48.3 micrograms, t = -2.21, P < 0.03). There was a statistically significant
      decrease in pre-fentanyl CHEOPS scores in the Post-Anesthesia Care Unit (PACU) in
      the ketorolac group (F (2, 30) = 5.34, P < 0.01), but not in the saline group (F
      (2.24) = 2.46, P > 0.05). In the first hour postoperatively, the CHEOPS
      demonstrated significant decreases in pain intensity scores in response to
      opioids, in both groups. In the PACU, children were unable to provide a self
      report of pain intensity potentially due to a variety of factors (e.g., emergence
      delirium, agitation, excitement, sedation, and/or pain). However, during the
      remainder of the postoperative stay, the photographic scale of the Oucher was a
      more valid measure of pain intensity than the CHEOPS.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7644240
TI  - Comments on Dr. J.E.L. Owen.

PMID- 7644239
TI  - Systemic adenosine infusion: a new treatment modality to alleviate neuropathic
      pain.
AB  - Adenosine, an endogenous antinociceptive compound acting in the central nervous
      system, was infused intravenously (50-70 micrograms/kg/min) to 2 patients with
      peripheral neuropathic pain. In 1 subject, spontaneous pain was alleviated, and
      tactile allodynia was essentially relieved during 40 min of infusion. Allodynia
      to warmth and touch were abolished in the other subject. In addition,
      hyperalgesia to pinprick was markedly attenuated as was pressure-induced
      allodynia. The reported effects lasted for hours after termination of the
      infusion. Our preliminary encouraging data call for further controlled studies of
      the potentially relieving effect of adenosine in painful neuropathic conditions.

PMID- 7644241
TI  - Comments on K.H. Njoo and E. Van der Does, PAIN, 58 (1994) 317-323.

PMID- 7644242
TI  - Comments on T.D. Nguyen.

PMID- 7644243
TI  - Cutaneous injection of the capsaicin analogue, NE-21610, produces analgesia to
      heat but not to mechanical stimuli in man.
AB  - Intradermal injection of the capsaicin analogue, NE-21610 (Procter and Gamble),
      inactivates nociceptors but not low-threshold mechanoreceptors in monkey. The
      present study examined the effects of cutaneous NE-21610 on heat and mechanical
      sensation in normal human volunteers. In the first series of experiments,
      subjects received intradermal (i.d.) injections (30 microliters) of the vehicle
      alone or with the drug (0.3, 3.0, 10 micrograms) into different sites on the
      volar forearm. Subjects were randomly assigned to 1 of 3 protocols to examine
      drug-evoked pain (n = 8), or alterations in pain to heat (n = 8) or mechanical (n
      = 8) stimuli induced by the drug. An additional 7 subjects rated pain to
      mechanical and heat stimuli before and after subcutaneous (s.c.) injections (300
      microliters) of the vehicle or drug (100 micrograms). The peak pain occurred at
      the time of injection, was of short duration, and was similar for vehicle and
      drug injections. A mild, dose-related pain followed that lasted up to 2 h. Von
      Frey thresholds for detection, sharpness, and pain at the injection site
      (measured 24 h after injection) were not significantly altered by either i.d. or
      s.c. drug administration. However, pain to stepped heat stimuli was reduced in a
      dose-dependent fashion for both types of injection. At the highest drug doses,
      analgesia to heat stimuli was still present 1 week after injection. Recovery of
      heat sensitivity occurred several weeks after injection. This dissociated loss of
      heat but not mechanical pain sensibility may be due to: (1) a selective action of
      the drug on heat transducers in nociceptors responsive to both heat and
      mechanical stimuli, or (2) a selective action on that subset of nociceptors
      responsible for signaling heat-evoked pain.

PMID- 7644244
TI  - The lack of hypoalgesic efficacy of H-wave therapy on experimental ischaemic
      pain.
AB  - The hypoalgesic effect of H-wave therapy (HWT) at various frequencies (2-60 Hz)
      was assessed using a standardised form of the submaximal effort tourniquet
      technique (SETT). Healthy human volunteers (n = 112; 56 men, 56 women) were
      required to attend on two occasions; on the first, baseline pain scores were
      obtained and on the second, 48 h later, subjects were randomly assigned to
      control, placebo or 1 of 5 H-wave treatment conditions. In the treatment groups 2
      self-adhesive electrodes were attached to the ipsilateral Erb's point and just
      lateral to the spinous processes of C6/C7. H-wave stimulation commenced 10 min
      prior to pain induction and continued throughout the 12-min duration of the
      technique. In the placebo group electrodes were attached as normal but leads were
      connected to a dummy power output. Analysis of variance of the differences in
      visual analogue scale and McGill Pain Questionnaire scores showed no significant
      differences in the treatment groups compared to placebo or controls. These
      results do not provide convincing evidence for any hypoalgesic effects of HWT at
      the frequency parameters stated on the experimental model of pain used.

PMID- 7644245
TI  - Pre-injury lidocaine treatment prevents thermal hyperalgesia and cutaneous
      thermal abnormalities in a rat model of peripheral neuropathy.
AB  - The effect of lidocaine pretreatment on thermal hyperalgesia and thermal skin
      asymmetries provoked by experimental mononeuropathy was investigated in rats.
      Forty anesthetized rats were given sciatic nerve ligatures according to the
      technique of Bennett and Xie. Rats were divided into 3 groups: 16 were ligated
      without lidocaine, 16 were ligated after lidocaine bathing of the nerve, and 8
      were ligated after systemic lidocaine (6-8 mg/kg). Six sham-operated rats for
      each group were also prepared. From the first postoperative day the responses to
      the hot-plate test were assessed daily for 4 weeks by tracking the paw-licking
      latency (PLL) for both hindpaws. Shorter or longer latencies on the operated side
      were respectively considered sign of hyperalgesia and hypoalgesia. Infrared
      thermographic images of plantar hindpaws were taken in 22 operated rats in the
      2nd postoperative week. Thermographic images of 8 non-operated rats were used as
      control. Animals operated without lidocaine exhibited shorter PLL (P < 0.001) and
      a decreased skin temperature on the operated side (P < 0.001). In the lidocaine
      pretreated rats, no paw-licking reflex was present for a variable postoperative
      period (1 week or more) and afterwards there was a trend toward recovery of
      normal PLL values at the 4th week; the hindpaw skin temperature was symmetrical
      and normal. Sham-operated rats had normal tests. It is postulated here that
      lidocaine prevents behavioral and thermal manifestation of mononeuropathy by
      blocking early afferent injury barrage.

PMID- 7644246
TI  - Relief of cholestatic pruritus by a novel class of drugs: 5-hydroxytryptamine
      type 3 (5-HT3) receptor antagonists: effectiveness of ondansetron.
AB  - The objective of the present study was to determine whether ondansetron, a
      specific serotonin type 3 receptor antagonist (5-HT3), relieves cholestatic
      pruritus in patients resistant to conventional antipruritic therapy
      (antihistamines and cholestyramine). In a placebo-controlled study the acute
      effect of an intravenous injection of ondansetron (4 mg, 8 mg) or placebo (NaCl
      solution) was tested in 10 patients (41-66 years of age; 4 men, 6 women) with
      cholestatic itch. A successful treatment was assessed when the intensity of itch
      was reduced by 50% or more within 2 h after injection of ondansetron. Intensity
      of itch was determined by the patients on a visual rating scale from 0 to 10.
      Ondansetron reduced or abolished pruritus within 30-60 min after injection. A 50%
      reduction of the intensity of itch was observed up to 6 h after injection of 8
      mg. The effect was reproducible in the same patient. In conclusion ondansetron is
      effective in the treatment of cholestatic itch. Serotonin may participate in the
      generation and/or sensation of cholestatic pruritus.

PMID- 7644247
TI  - A double-blind investigation of the hypoalgesic effects of transcutaneous
      electrical nerve stimulation upon experimentally induced ischaemic pain.
AB  - The hypoalgesic effect of transcutaneous electrical nerve stimulation (TENS) at 2
      different frequencies was assessed under double-blind conditions using a
      standardised form of the submaximum effort tourniquet technique. For the purpose
      of pain induction, 32 healthy naive female subjects attended on 2 occasions, the
      first during which baseline data were obtained and the second during which the
      women were randomly allocated to 1 of 4 groups: Control, Placebo, TENS-1 (110 Hz)
      or TENS-2 (4 Hz). In the treatment groups, 2 hydrogel electrodes were positioned
      over Erb's point and lateral to C6 and C7 vertebral spines. A TENS machine was
      applied for 10 min before the cuff was inflated and remained on for the duration
      of the pain procedure (12 min). Pain was measured using visual analogue scales
      (VAS) and the McGill Pain Questionnaire (MPQ) to assess 'current pain intensity'
      and 'worst pain experienced', respectively. Analysis of VAS scores showed
      significant differences between groups (ANOVA, P = 0.02), with the TENS-2 group
      showing a greater hypoalgesic effect than the other groups. One-factor ANOVA
      showed no significant differences in MPQ scores between groups. The results of
      this study have provided evidence of the hypoalgesic effects of TENS upon
      experimental ischaemic pain which were found to be frequency specific with the
      lower frequency used here (4 Hz) demonstrating the only significant effect.

PMID- 7644248
TI  - Morphine-6-glucuronide concentrations and opioid-related side effects: a survey
      in cancer patients.
AB  - The active morphine metabolite, morphine-6-glucuronide (M-6-G), may contribute to
      both the analgesia and the adverse effects observed during morphine (MOR)
      therapy. To evaluate the relationship between M-6-G and adverse effects, we
      measured steady-state plasma concentrations of MOR and M-6-G and concurrently
      noted the presence or absence of moderate to severe cognitive impairment or
      myoclonus in 109 cancer patients who were receiving either oral (n = 71) or
      parenteral (n = 38) morphine. MOR and M-6-G plasma concentrations were determined
      by HPLC with electrochemical detection. The presence of cognitive impairment or
      myoclonus was analyzed in relation to molar M-6-G/MOR ratio, age, morphine dose,
      the use of other centrally acting drugs, renal function (blood urea nitrogen
      (BUN) and serum creatinine), hepatic function (serum bilirubin, serum glutamic
      oxalacetic transaminase (SGOT), and alkaline phosphotase) and serum lactate
      dehydrogenase (LDH). The patient population consisted of 60 women and 49 men. The
      mean age was 51.5 years (range: 10-85 years). The mean morphine dose (total dose
      prior 48 h) was 486 mg (range: 40-4800 mg) for the oral group and 931 mg (range:
      (10-9062 mg) for the parenteral group. The mean molar M-6-G/MOR ratios were 6.1
      (SD: 18.2; range: 0.01-153.3) for the oral treatment group and 2.7 (SD: 4.16;
      range: 0.05-23.8) for the parenteral treatment group. Overall, the M-6-G/MOR
      ratio demonstrated a moderate but significant correlation with BUN (r = 0.4; P <
      0.001) and creatinine (r = 0.45; P < 0.001) levels, but not with the other
      clinical variables examined.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7644249
TI  - Intrathecal administration of high-dose morphine solutions decreases the pH of
      cerebrospinal fluid.
AB  - Terminally ill patients suffering from intractable cancer pain are treated in our
      hospital on an outpatient basis with a percutaneous intrathecal (i.t.) catheter
      and a portable pump delivering morphine continuously. In a patient showing an
      increased demand of morphine the dose was raised from 1.5 to 2 mg/h, but pain
      intensity did not decrease. Subsequently a 1.5 ml dose of 5% lidocaine was
      administered; however, no motor or sensory block was observed. After controlling
      the catheter position and passage through the catheter, a sample of cerebrospinal
      fluid (CSF) was taken and the pH was measured. It was found to be outside the
      physiological range of 7.19 (normal range: 7.27-7.37), possibly explaining the
      decreased activity of the local anesthetic. The purpose of this study was to
      determine the influence of morphine, with or without sodium metabisulfite, on pH
      in vitro, using artificial CSF (ACSF) and on pH in vivo during i.t.
      administration of morphine. An in vitro model was used to measure pH changes by
      adding a morphine solution (concentrations of 0.5, 2, 5 and 10 mg/ml) with and
      without sodium metabisulfite to ACSF solutions (Elliott B). Fourteen patients
      were consecutively selected for continuous administration of morphine. An i.t.
      catheter was inserted, tunnelled and connected with an external pump (Provider
      5500, Abbott, Chicago, IL). CSF was aspirated and pH was measured with a blood
      gas system (Ciba-Corning 288, Medfield, USA). In vitro, morphine solutions with
      or without sodium metabisulfite added to an Elliott B solution (pH = 7.47, 37
      degrees C) caused a concentration-related decrease in pH.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7644250
TI  - Prevalence, characteristics, and impact of postmastectomy pain syndrome: an
      investigation of women's experiences.
AB  - Postmastectomy pain (PMP), a distinctive postsurgical neuropathic pain syndrome,
      has been thought to be consequence of 4-6% of surgical procedures for cancer of
      the breast, but remains understudied and poorly documented. In this cross
      sectional descriptive study, a convenience sample of 95 women who had undergone
      breast cancer surgery was recruited from 16 ambulatory care sites. Prevalence,
      characteristics, and impact of the PMP syndrome were investigated using a medical
      record review, a patient information questionnaire, a cancer pain questionnaire
      and the McGill Pain Questionnaire. A 20% prevalence rate of the PMP syndrome was
      found. Women experiencing the syndrome reported chronic, stable pain of long
      duration that began shortly after surgery. They described paroxysms of
      lancinating pain against a background of burning, aching, tight constriction in
      the axilla, medial upper arm, and/or chest that significantly interfered with the
      performance of daily occupational and domestic activities. Data suggest that
      these women were undertreated and generally obtained poor pain relief from their
      symptoms.

PMID- 7644251
TI  - Evidence for a biopsychosocial model of cancer treatment-related pain.
AB  - The contribution of non-biomedical factors to the experience of pain in the
      cancer patient has not been well established. Although intensity of pain reports
      cannot be fully explained by extent of identifiable nociception or neuropathy,
      behavioral factors have been only modest predictors of cancer pain report. Most
      studies that have demonstrated associations between pain and behavioral factors
      were conducted with highly selected groups of patients with all data collected
      concurrently. Thus the predictive value of the behavioral factors has been
      indeterminable. In this study, 358 bone marrow transplant patients (196 male, 162
      female) completed pretransplant biomedical, physical functioning, psychological
      and social evaluations. For 25 days following transplantation, patients completed
      daily visual analogue scale oral pain reports and nurses recorded opioid use. At
      least once a week oral medicine staff completed a standardized, validated measure
      of observable oral mucositis as a measure of nociception. Results indicated that
      psychological and social variables were significant predictors of pain in this
      sample. Distress, particularly distress specific to the transplant, was the
      strongest predictor, while self-efficacy and coping style were weaker, but
      significantly associated with pain report for either men or women. While the
      psychological and social variables were significant predictors of pain, most of
      the variance in pain report was explained by biomedical variables rather than
      psychological or social variables. These results are consistent with those of
      previous research and indicate that biopsychosocial associations predate the
      onset of pain, but are at best modest predictors of cancer patients who will
      report greater or lesser pain. Clinical applications and limits of these data are
      discussed, particularly in relation to emotional distress, coping style and the
      differences found in predicting pain in men and women.

PMID- 7644252
TI  - Cluster analyses of pain patients' responses to the SCL-90R.
AB  - This study sought to identify distinct subgroups of chronic pain patients based
      on responses to the Symptom Checklist 90-revised (SCL-90R), a measure of
      psychological distress. Two scoring methods were used: the standard scoring that
      accompanies the manual, and a scoring method based upon factor scores obtained in
      an earlier study using low back pain patients. Two separate cluster analyses
      assigned patients into 2 groups: one based on standard scores and one based on
      factor scores. Results of this study support the hypothesis that distinct and
      replicable subgroups of chronic pain patients can be identified using the SCL
      90R. Depending upon group membership, patients significantly differed on measures
      of qualitative pain and quantitative pain report, depressive symptoms, medication
      usage, and pain-related behaviors. This study supports the use of SCL-90R factor
      scoring with pain patients as greater differentiation between clusters was found
      for pain report and pain-related behavior when this method was used. Guidelines
      for clinical application of SCL-90R cluster groups is provided.

PMID- 7644253
TI  - Chronic pain and depression: role of perceived impact and perceived control in
      different age cohorts.
AB  - Chronic pain adversely affects individuals' physical as well as emotional well
      being. A cognitive-behavioral model has been proposed to explain the role of
      cognitive appraisal variables in mediating the development of emotional distress
      following pain of long duration. There is little evidence linking the prevalence
      of depression in chronic pain patients to life stage, but there are suggestions
      in the literature that the link between medical illness and depression may be
      stronger in elderly patients. One purpose of this study was to replicate the
      efficacy of a previous study of the cognitive-behavioral mediation model in
      explaining the association between pain and depressed affect. A second purpose of
      this study was to extend the cognitive-behavioral model to evaluate relationships
      among pain, cognitive appraisal variables, and depressive affect in the elderly
      chronic pain population. One hundred chronic pain patients were divided into two
      age groups (< or = 69 years and > or = 70 years). A path analysis conducted for
      the total sample supported the cognitive-behavioral mediation model of depression
      in chronic pain, in which cognitive appraisal variables mediate the pain
      depression relationship. Correlations among variables in each of the two age
      groups, however, revealed different patterns of association. Consistent with the
      cognitive-behavioral model, the younger patients demonstrated a low and non
      significant correlation between pain severity and depression (r = 0.01).
      Conversely, a strong direct association was observed in the older patients
      between these variables (r = 0.51). These results suggest that the relationship
      between pain and depression varies substantially depending upon age cohort.

PMID- 7644254
TI  - Development and evaluation of the management of the neuropathic bladder.

PMID- 7644255
TI  - The Stockholm spinal cord injury study: 1. Medical problems in a regional SCI
      population.
AB  - Out of a regional traumatic spinal cord injury population consisting of 379
      individuals, 353 (93.1%) participated in the present study. Subjects were
      individually interviewed using semi-structured protocols. In addition, previous
      medical records were available for over 96% of subjects, and were used in all
      these cases to minimise recall bias. Cause of injury, prevalence of present
      medical symptoms and occurrence of medical complications in the post-acute, post
      discharge phase were recorded. Neurological classification was verified by
      physical examination according to ASIA/IMSOP standards. Many subjects had
      experienced complications since discharge from initial hospitalisation,
      especially urinary tract infections, decubitus ulcers, urolithiasis, and
      neurological deterioration. Prevalence of medical symptoms was also high. More
      than 41% of subjects with spastic paralysis reported excessive spasticity to be
      associated with additional functional impairment and/or pain. Almost two-thirds
      of subjects reported significant pain, with a predominance of neurogenic-type
      pain. Bladder and bowel dysfunction were each rated by nearly 41% of subjects as
      a moderate to severe life problem. As expected, sexual dysfunction was also
      commonly reported. Prevalence of reported symptoms by general systems review was
      high, particularly fatigue, constipation, ankle oedema, joint and muscle
      problems, and disturbed sleep. However, lack of adequate normative data precludes
      comparison with the general population. The frequent occurrence of reported
      medical problems and complications support advocacy of comprehensive, life-long
      care for SCI patients. The commonly reported problems of neurogenic pain and
      neurological deterioration, in particular, require more attention, as these
      symptoms are not seldom ominous, either by virtue of their impact on quality of
      life, or because of underlying pathology.

PMID- 7644256
TI  - Utilization and effectiveness of methylprednisolone in a population-based sample
      of spinal cord injured persons.
AB  - The announcement and publication of the second National Acute Spinal Cord Injury
      Study (NASCIS II) project's findings regarding the role of high dose
      methylprednisolone in improving neurological outcomes following acute traumatic
      spinal cord injury generated widespread excitement and interest. To determine the
      association between this interest and actual use and implementation of the
      protocol, Colorado's comprehensive population-based spinal cord injury
      surveillance data were examined. The medical records of 218 SCI survivors injured
      between May 1, 1990 and December 31, 1991, and of 145 persons spinal cord injured
      2 years later, during 1993, were reviewed to determine the rapidity and extent of
      NASCIS II implementation by Colorado's hospitals, factors associated with use and
      non-use of the protocol, changing usage trends over time, and the short term
      neurological outcomes of patients who received the protocol. Clear documentation
      of the protocol's usage was present for only 46% of the reported patients'
      medical records in 1990-91, and 61% in 1993. Small, emergency triage facilities
      were significantly more likely to use the protocol than larger acute care
      hospitals, and patients with initially incomplete injuries were less likely to
      receive the drug. There were no significant differences in neurological outcomes,
      using the Frankel classification system, between those who received the protocol
      and those who did not. The limitations and implications of these findings are
      discussed.

PMID- 7644257
TI  - Epidemiology of spinal cord injuries in Novosibirsk, Russia.
AB  - The incidence of spinal cord injuries (SCI) in Novosibirsk is 29.7 per million
      per year. Almost all of these SCI patients (94.3%) are hospitalized to our
      clinic. Over the past 5 years (since 1989), a total of 196 patients with SCI were
      admitted. SCI were distributed as follows: cervical, 96 patients (49.0%);
      thoracic, 54 (27.5%); and lumbar, 46 23.5%). SCI was diagnosed using computed
      tomography (CT), magnetic resonance imaging (MRI), pneumomyelography,
      epidurography, radiography and electrophysiological methods (neuromyography,
      evoked potentials). All patients had a neurological deficit of varying degree;
      Frankel grade A, 64 patients (32.7%); B, 22 (11.2%); C, 67 (34.2%); and D, 43
      (21.9%). Almost 40% (39.7%) of the patients had unstable fractures, most of them
      being in the cervical spine. One hundred and ninety patients were operated on, 52
      within 3-4 h after trauma. Several types of operation were used: anterior
      decompression (106 patients); posterior decompression (64 patients);
      omentomyelopexia (seven patients); meningomyeloradiculolysis (13 patients).
      Conservative treatment ('halo' traction) was applied in six patients. No patient
      was made worse because of the surgery. Twenty four patients had a complete
      neurological recovery, 113 patients could be reclassified into a higher group
      (Frankel classification), and 59 patients had no neurological improvement. The
      overall mortality was 16.8% (13.7 postoperatively).

PMID- 7644258
TI  - Lower urinary changes over time in suprasacral spinal cord injury.
AB  - This paper reviews 179 patients (23 females and 156 males) with suprasacral
      spinal cord injury (SCI) who underwent videourodynamic evaluation to compare
      maximum detrusor pressure, compliance, and trabeculation with methods of bladder
      management, years post-injury, and age. The patients were divided into four
      groups based on mode of bladder management: clean intermittent catheterization
      (CIC), indwelling catheter (IND), external collector (EC), and voiding (V).
      Maximum pressure decreased significantly with increasing age for those using EC
      (P < 0.01) and CIC (P < 0.05). Maximum pressure also decreased significantly with
      years post-injury for patients on EC (P < 0.01) and was highest the first decade
      after injury and progressively decreased through the fifth decade. Post-hoc tests
      indicated more severe trabeculation in patients in the EC group than in either
      the CIC or IND groups. Age and trabeculation did not correlate in those on EC. We
      conclude that patients with long-standing suprasacral SCI using EC are more
      likely to have lower detrusor pressures than are those with less chronic SCI.
      This finding may reflect the effects of age as well as reduced survival in those
      using EC with chronically elevated detrusor pressure.

PMID- 7644259
TI  - Influence of minor trauma to the neck on the neurological outcome in patients
      with ossification of the posterior longitudinal ligament (OPLL) of the cervical
      spine.
AB  - The influence of minor trauma to the neck on the neurological outcome in patients
      with ossification of the posterior longitudinal ligament (OPLL) of the cervical
      spine was evaluated retrospectively. Out of 118 patients treated in our clinic
      for cervical OPLL between 1976 and 1992, 27 had sustained minor trauma to the
      cervical spine. Of these 27 patients, 13 developed myelopathy, seven showed
      deterioration of preexisting myelopathy, and no neurological change was observed
      in seven patients. Regarding the relationship between the diameter of the
      residual spinal canal and the neurological outcome in these 27 patients, 18 out
      of the 19 patients with a narrow residual spinal canal (< 10 mm) developed
      neurological deterioration, whereas that occurred in only two of the eight
      patients with a wider spinal canal (> or = 10 mm). Although the severity of
      myelopathy and the transverse area of the spinal cord measured from T1-weighted
      magnetic resonance images, in patients who had sustained minor trauma was not
      statistically different from patients without trauma, neurological recovery after
      surgical treatment was poorer in the former group than in the latter. These
      results indicate that even indirect minor trauma to the neck can cause
      irreversible changes in the spinal cord if there is marked stenosis of the
      cervical spinal canal; such patients who are at risk, must be educated, and
      should be told to avoid even minor injuries at any cost.

PMID- 7644260
TI  - Sexual activities and concerns in persons with spinal cord injuries.
AB  - A survey of sexual activity and concerns of people with spinal cord injury living
      in the community was undertaken. A questionnaire was sent to 144 people, and 102
      replies were collected. Of the sample, 59.8% reported having engaged in some
      aspect of sexual life. Sexual life ranked the lowest in terms of importance with
      respect to other aspects of life. However, 47.1% answered that they were not
      satisfied with their sexual life. It was indicated that the provision of
      information regarding sexuality should remain a high priority for health care
      providers.

PMID- 7644261
TI  - Lumbar spinal stenosis causing intermittent priapism.
AB  - The current report concerns the unusual symptom of intermittent priapism, or what
      may be termed 'involuntary penile erection', associated with proven degenerative
      lumbar spinal stenosis. Seven patients who were treated for intermittent
      claudication and spontaneous priapism during walking were studied in terms of
      clinical presentation, imaging findings, and some electrophysiological testing.
      Varying degrees of walking and standing tolerance with these unusual symptoms
      appeared to be correlated with cauda equina constriction as was seen by
      radiological imaging. Although not statistically valid, external urethral
      sphincter evoked electromyography suggested the possibility of monitoring the
      unusual symptom during walking. Surgical spinal decompression is recommended to
      alleviate this symptom and the claudication.

PMID- 7644262
TI  - Electrorectogram study of the neuropathic rectum.
AB  - The rectal electrical activity was studied by electrorectogram (ERG) in 28
      patients with spinal cord injury (SCI) (mean age 46.6 years, 18 men and 10 women)
      and nine healthy volunteers (controls). Nineteen patients had an upper motor
      neuron lesion (UMNL) and 9 a lower motor neuron lesion (LMNL). The ERG was
      recorded by a monopolar silver-silver chloride electrode applied to the rectal
      mucosa by suction. Simultaneous recording of the rectal and rectal neck pressures
      was performed. At least four recording sessions of 120 min each were done for
      every subject. No complications were encountered during the test. The ERG in
      normal subjects showed pacesetter potentials (PP) with a regular rhythm and
      constant frequency and were reproducible in the individual subject. PP were
      followed by action potentials (AP) which had an inconsistent frequency and were
      associated with increased rectal pressure. The ERG in UMNL patients exhibited
      'dysrhythmia' with irregular frequency, amplitude and velocity. The AP did not
      show in any recording. LMNL patients had a 'silent' ERG. In conclusion, two
      patterns of ERG could be identified in SCI patients: dysrhythmic and silent. The
      cause of the disordered ERG could be due to derangement of the intrinsic rectal
      conducting system.

PMID- 7644263
TI  - Early surgery for thoracolumbar spinal cord injury: initial experience from a
      developing spinal cord injury centre in India.
AB  - The spinal cord injury centre of Nizam's Institute of Medical Sciences, Andhra
      Pradesh, India has been functioning now for 8 months and offers its services to
      the population of 80 million in the state. To date, 92 patients with a spinal
      cord injury have been treated; 51 had a thoracolumbar spinal injury. This report
      presents the results of the management of these 51 patients. Preoperatively both
      CT and MRI were performed and the radiological findings were correlated with
      outcome. Twenty five had a thoracic and 26 a lumber location. Twenty nine
      patients underwent surgical treatment (15 thoracic and 14 lumbar) and the others
      were treated conservatively (10 thoracic and 12 lumbar). All these operations
      were carried out within 2 weeks following trauma, and methylprednisolone therapy
      was instituted in those who reached the hospital early. Contraindications for
      surgery included a delay in admission of more than 3 weeks following trauma, a
      focus of sepsis, bedsores, a generalised bone disorder such as osteopenia, and
      medical illnesses. Transpedicular screw-plate fixation was performed in 27
      patients, and two patients underwent decompressive laminectomy and interlaminar
      bone and wire fixation. Delayed spinal decompression was offered to one patient
      to relieve radiculopathy. Fracture-dislocation spinal injury and those with
      transection of the spinal cord had the worst outcome, whilst patients with a
      wedge compression fracture and cord oedema fared better. Operated cases had a
      shorter hospital stay, and complications of immobilisation were limited. Positive
      psychological influence of mobilisation and early acclimatisation to the altered
      style of living with their disability were the most significant outcomes
      following surgery.

PMID- 7644264
TI  - Surgical treatment guided by spinal cord evoked potentials for tetraparesis due
      to cervical spondylosis.
AB  - Sixteen consecutive patients who were unable to ambulate independently due to
      cervical spondylotic myelopathy were treated surgically with the guidance of
      spinal cord evoked potentials (SCEPs). The SCEPs were recorded intraoperatively
      with needle electrodes inserted into serial cervical intervertebral discs after
      caudal epidural stimulation. Despite the presence of multiple extradural defects
      and/or cord compression seen on MRI, anterior decompression followed by fusion
      was able to be focused on a single level where the distinct change in waveform of
      the SCEP suggestive of spinal conduction block was revealed. Excellent
      neurological improvement resulted from the operation and all patients followed up
      for a period of more than 6 months were found to be ambulatory without walking
      aids.

PMID- 7644265
TI  - Repairing spinal roots after brachial plexus injuries.
AB  - The problems of repairing spinal roots after brachial plexus avulsion injuries
      are discussed in the light of current surgical diagnosis and treatment. An
      advancing understanding of the cellular mechanisms of nerve regeneration and
      progress in surgical technology indicates a possibility for the repair at least
      of ventral roots with grafts which may be of neural or non-neural origin.
      Enhancement of the regenerative properties may further be made possible by the
      application of neurotrophic factors at the repair site or centrally. The short
      and long-term implications of current research into these methods are discussed.

PMID- 7644266
TI  - Spinal cord injury in a child: a long term follow-up study. Case report.
AB  - The main features of spinal cord injuries in children are known to be that (1)
      plain radiographs do not show the bony injury; (2) many of the injuries are
      complete spinal cord injuries; (3) many involve the upper thoracic spine; and (4)
      the duration of spinal shock is short. Complications such as pressure sores occur
      just as easily in children as in adults and the injuries are intractable. Typical
      complications in children with spinal cord injuries are spinal deformity and hip
      dislocation. We discuss a patient with a C7 spinal cord injury caused by a fall
      when the patient was 3 years old, and the physical complications occurring during
      the 15 years following the injury.

PMID- 7644267
TI  - Lithotripsy in SCI patients.

PMID- 7644268
TI  - Restriction fragment length polymorphism analysis of two hemagglutinin loci,
      serotyping and agglutinating activity of Porphyromonas gingivalis isolates.
AB  - Restriction fragment length polymorphisms (RFLPs) of two hemagglutinin loci were
      analyzed in 36 Porphyromonas gingivalis isolates from human and monkey origins
      using portions of hagA and hagB as probes. The P. gingivalis strains were
      differentiated into 9 RFLP groups based on the heterogeneity of the hagA locus
      and 10 different groups based on hybridization with hagB. Homology to hagA was
      detected in all human derived and all but three monkey derived strains. All P.
      gingivalis isolates exhibited DNA homologous to hagB. Multiple alleles of the
      hemagglutinin genes were detected for most P. gingivalis strains. No DNA
      homologous to either hemagglutinin gene could be detected in 6 other bacterial
      species tested. Serotyping and hemagglutination titers of each P. gingivalis
      isolate were obtained in an attempt to establish a correlation between these
      pheno-typic parameters and RFLP group. Although no correlations were found with
      these parameters, a correlation between RFLP group and invasiveness in the mouse
      abscess model was noted.

PMID- 7644269
TI  - Clonal diversity of the Streptococcus mitis biovar 1 population in the human oral
      cavity and pharynx.
AB  - A total of 250 isolates of oral streptococci were recovered from swabs of
      oropharyngeal surfaces of 3 members of one family. All isolates were examined by
      biochemical and serological means, and 106 isolates were identified as
      Streptococcus mitis biovar 1. These were typed by restriction endonuclease
      analysis using the enzymes EcoRI and HaeIII and further characterized by their
      whole-cell polypeptide profile patterns in sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis. In addition, rabbit antisera raised against 8 reference
      strains of oral streptococci were used to characterize representative isolates
      both by their carbohydrate and protein antigens by Ouchterlony and Western blot
      analyses. Very limited biochemical diversity was observed among the 106 S. mitis
      biovar 1 isolates. In contrast, 24 different genotypes defined by restriction
      endonuclease analysis were detected, and each individual carried 6-13 types.
      Limited sharing of genotypes was observed between the 3 members of the same
      family and between the pharyngeal and buccal mucosa of single individuals. The
      antigenic analyses showed remarkable antigenic diversity between the 24
      genotypes. The results provide a basis for studying the population dynamics of an
      oral commensal species and its interaction with the salivary immune system.

PMID- 7644270
TI  - Intrafamilial similarity in immunoblot profiles of salivary immunoglobulin A
      antibody activity to oral streptococci.
AB  - Analysis of the salivary immunoglobulin A (IgA) antibody activity to antigens
      separated from oral streptococci was carried out on 49 individuals in 11
      families. The aim of this study were to i) study the human salivary IgA activity
      within families to antigens separated from reference strains of Streptococcus
      mutans, Streptococcus sobrinus and Streptococcus parasanguis and ii) to search
      for potential differences in the salivary IgA activity to the streptococcal
      antigens several years apart. The immunoblot revealed similarity in saliva IgA
      response within the families. A majority of the bands, approximately 7 (median)
      for each extract was found in both child and parent. A few bands (approximately
      3) were found in parents but not in children. Only one to two bands were found in
      children's saliva without a corresponding band in any of the parents. The
      antibody activity of saliva samples obtained several years apart was essentially
      unchanged, especially considering the total number of bands. Differences in the
      relative intensity of the bands could be seen, and a few bands appeared only in
      some immunoblots for a specific subject. For 3 of 4 children participating in the
      longitudinal study, more bands against mutans streptococci appeared with age.

PMID- 7644271
TI  - Lactoferrin interaction with Actinobacillus actinomycetemcomitans.
AB  - The interaction of lactoferrin with Actinobacillus actinomycetemcomitans was
      examined in a 125I-labeled protein binding assay. The binding of human and bovine
      lactoferrins reached maximum within 1 h. Lactoferrin binding to the bacterium was
      pH-dependent and reversible. Scatchard analysis indicated the existence of two
      different types of binding sites on the bacterium, one with a high affinity
      constant k alpha approximately 8.8 x 10(-7) M) and the other with a low one (k
      alpha approximately 1.8 x 10(-6) M). Bacteria in the exponential phase of growth
      showed higher binding than cells in the stationary phase. Bacteria grown in
      medium containing serum and/or lysed erythrocytes bound lactoferrin to a lesser
      extent. Heat-inactivated serum, lysed erythrocytes and other proteins such as
      mucin and laminin inhibited lactoferrin binding to A. actinomycetemcomitans in a
      competitive binding assay. Sodium dodecyl sulfate polyacrylamide-gel
      electrophoresis and Western blot analysis of the cell envelope as well as the
      outer membrane of A. actinomycetemcomitans revealed lactoferrin-reactive protein
      bands at 29 kDa and 16.5 kDa. The 29-kDa band displayed a heat-modifiable
      lactoferrin-reactive form with a molecular weight of 34 kDa. Neither proteinase K
      treated cell envelope nor lipopolysaccharide of this bacterium showed reactivity
      with lactoferrin. These data suggests a specific interaction of lactoferrin with
      outer membrane proteins of A. actinomycetemcomitans.

PMID- 7644272
TI  - Occurrence of enteric rods, staphylococci and Candida in subgingival samples.
AB  - The frequency and percentage of enteric rods, staphylococci and Candida were
      determined in 973 subgingival samples collected from 535 patients subjected to
      different periodontal treatment procedures. The analysis was performed with
      culture technique using selective and nonselective media. One or more organisms
      were detected in 65.5% of the samples and in 76.7% of the patients. In most
      samples enteric rods, staphylococci and/or Candida constituted a small amount of
      the total microbial viable count. Enteric rods exceeded 10% of the total viable
      count in 30 samples. Staphylococci occurred in more than 10% in only 3 samples.
      In these 3 samples, enterics constituted more than 10% of the total viable count.
      Candida was not found to exceed 10% of the total viable count in any of the
      samples. No statistically significant correlation was found between the presence
      of any of the target microorganisms and kind of periodontal treatment procedure
      received, antibiotic administration or sample transport time.

PMID- 7644273
TI  - Inhibition of streptococcal growth, F-ATPase and pyrophosphatase by
      diphosphonates.
AB  - 1-Hydroxyethane-1,1-diphosphonate (EHDP) and a variety of other diphosphonates,
      and also pyrophosphate, at millimolar levels were found to inhibit the growth of
      Streptococcus mutans GS-5. Inhibition appeared to be due mainly to chelation of
      Mg2+ and could be readily reversed through addition of Mg2+, or less effectively,
      by other divalent cations. The trianionic forms of the diphosphonates or
      pyrophosphate were more effective inhibitors than the dianionic forms.
      Diphosphonates and pyrophosphate did not inhibit glycolysis by S. mutans, assayed
      in terms of glucose utilization, or arginolysis by Streptococcus rattus FA-1,
      assayed in terms of ammonia production. However, they did act as buffers to
      moderate pH changes. Diphosphonates also were inhibitors of the F-ATPase of S.
      mutans by complex mechanisms only partly reversible with divalent cations. They
      also were inhibitors of the pyrophosphatase of the organism. However, intact
      cells were impermeable to the compounds, and inhibition of cytoplasmic or
      membrane enzymes did not appear to be involved in growth inhibition.

PMID- 7644274
TI  - Identification of salivary proteins inhibiting herpes simplex virus 1
      replication.
AB  - Salivary proteins play an important role in the maintenance of the oral ecology.
      Previous studies have indicated that human submandibular-sublingual and parotid
      salivas can selectively suppress the in vitro infectivity of herpes simplex virus
      1. The purpose of this study was to identify the salivary components in human
      submandibular-sublingual saliva that modulate in vitro infectivity. Assessment of
      the interaction of viral particles with salivary components was accomplished
      using an in vitro solid-phase assay. These experiments revealed that herpes
      simplex virus particles selectively interact with the members of the salivary
      proline-rich protein and cystatin families. Subsequent yield reduction assays
      demonstrated the ability of proline-rich proteins and salivary cystatins to
      inhibit the viral replication, with basic proline-rich peptides being more
      effective. Subsequent assays suggest that basic proline-rich peptides reduced the
      virus titer by interfering with penetration and/or cellular processing of virus
      within the target cell. Collectively, these results further suggest that salivary
      proteins have an important role in the host defense mechanism against recurrent
      herpesvirus infection.

PMID- 7644275
TI  - Detection of human papillomavirus in oral lesions using commercially developed
      typing kits.
AB  - Biopsy material from 20 oral lesions (19 condylomas and 1 squamous papilloma)
      previously shown to contain human papillomavirus (HPV) 6 and HPV 11 sequences by
      in situ hybridization were examined using 3 commercially available HPV typing
      kits. Sensitivity and specificity were compared with in-house methods. Previous
      in situ hybridization had detected HPV 6b in 11 (55%) of the biopsies, HPV 6 and
      11 in 7 (53%) and HPV 11 alone in 1 biopsy. Only one of the commercial assays
      (assay 1) detected HPV in all 20 biopsies (11 positive for HPV 6b only, 1 for HPV
      11 only and 7 for HPV 6b and 11). The wide spectrum probe of assay 2 detected HPV
      in only 10 (50%) of the biopsies, and in a further 2 biopsies the hybridization
      results were difficult to interpret because of background staining. Assay 3 used
      a combined HPV 6/11 probe and detected HPV in 15 (75%) of the biopsies. Clear
      hybridization signals were demonstrated in the intermediate and upper layers only
      of squamous epithelium, as expected from the known association of HPV replication
      with epithelium differentiation. In most specimens background levels were not a
      problem, and all commercial assays were easy to use. The findings are discussed
      in the context of the digestion procedures, sensitivity of the probes provided
      and the conditions of hybridization, all of which would influence the detection
      of HPV.

PMID- 7644276
TI  - Distribution and characterization of plasmids in oral anaerobic spirochetes.
AB  - Fifteen oral spirochete strains belonging to the species Treponema denticola,
      Treponema vencentii and Treponema socranskii as well as 9 fresh clinical isolates
      were screened for the presence of extrachromosomal plasmid DNA by a modified
      alkaline lysis procedure. A 2.6-kb plasmid was detected in both T. denticola ATCC
      33520 and T. denticola e'. The 2.6-kb plasmid from T. denticola e' was shown to
      be similar to pTD1, previously reported by Ivic et al. in T. denticola ATCC 33520
      on the basis of molecular weight, restriction endonuclease profile and DNA:DNA
      hybridization. T. denticola ATCC 33520 and T. denticola e' share 65% DNA homology
      and belong to different serological groups. This dissimilarity has been
      reconfirmed by specific immunofluorescence using polyclonal and monoclonal
      antibodies. A plasmid-free T. denticola ATCC 33520 was identified. Comparative
      studies have shown no antigenic, morphological, or genetic differences between
      the plasmid-bearing and the plasmid-free strain. In addition, screening of fresh
      clinical isolates of spirochetes revealed the presence of a 4.2-kb plasmid in 4
      of these strains.

PMID- 7644277
TI  - The passing of a hero from our generation.

PMID- 7644278
TI  - Comparison of brachial and calf blood pressures in infants.
AB  - PURPOSE: To compare brachial and calf blood pressures in infants under one year
      of age using the same size blood pressure cuff. METHODOLOGY: A convenience sample
      of 79 infants ages 4-300 days was selected from the General Pediatric, Pediatric
      Special Care, and Pediatric Intensive Care units in an acute care hospital
      located in the southern United States. Difference between brachial and calf blood
      pressures were compared using a paired t-test and defining the range of
      difference for 95% of the sample. RESULTS: There was no statistically significant
      difference in brachial and calf blood pressure measurements when assessed by
      paired t-test. The range of difference for 95% of the sample merits further
      clinical attention. CONCLUSION: Calf blood pressure measurements can be assessed
      routinely on infants under one year of age but it is important to consistently
      compare calf pressures to calf pressures and brachial pressures to brachial
      pressures.

PMID- 7644279
TI  - Continuous nebulization: a treatment modality for pediatric asthma patients.
AB  - Asthma is the most common of the chronic lung diseases diagnosed in children and
      accounts for a large percentage of emergency department/hospital admissions.
      Recently, the use of continuous administration of Beta-adrenergic agents has been
      found to be a safe and effective method of therapy for the pediatric patient
      experiencing severe asthma. An understanding of equipment, monitoring parameters,
      and nursing implications can help prepare pediatric nurses to provide care for
      children receiving continuous nebulization. An urban hospital in the northeastern
      United States organized a multidisciplinary team to investigate the use of
      continuous nebulization of Beta 2 agonists in the care of the pediatric patient
      experiencing an acute asthma episode.

PMID- 7644280
TI  - Pediatric resuscitation: development of a mock code program and evaluation tool.
AB  - Effective and efficient resuscitation skills are especially significant for
      pediatric care providers because of the increased neurologic morbidity and
      mortality associated with pediatric arrests. A mock code system was initiated to
      assess and enhance the competency of the medical and nursing staff who respond to
      pediatric arrests in all areas of an acute care general hospital. Two mock codes
      are conducted each month using a data collection tool. All of the critical skills
      involved in a pediatric resuscitation are listed in the tool and each skill is
      evaluated as met or not met. The tool identifies areas for further education and
      quantifies improvement in skills over a period of time. In addition, the
      Pediatric CPR Committee uses the data from the mock codes to initiate systems and
      equipment improvements.

PMID- 7644281
TI  - Quality improvement study of day surgery for tonsillectomy and adenoidectomy
      patients.
AB  - Ongoing efforts to contain costs in health care have had an impact on the
      delivery of care in the ambulatory setting. Many patients previously admitted to
      the hospital for an overnight stay are now discharged home within hours of
      surgery. In response to concerns raised by nursing staff about same-day discharge
      of patients undergoing tonsillectomy and adenoidectomy (T&A), a quality
      improvement (QI) study was conducted. Data from more than 150 families over a 2
      year period were collected, using the clinical indicator of safe discharge. The
      data were obtained during the patient's recovery room stay, the first post
      operative day, and 2 weeks after surgery. Findings suggested that some of the
      teaching done by nurses was useful and some needed revision to meet patients'
      needs. Changes regarding pain management, fluid management, and post-operative
      bleeding were addressed.

PMID- 7644282
TI  - GM-CSF clinical trials: pediatric aplastic anemia and Fanconi's anemia.
AB  - Two clinical trials were undertaken to evaluate the effect of human recombinant
      granulocyte-macrophage colony stimulating factor (GM-CSF) in pancytopenic
      pediatric patients with aplastic anemia and Fanconi's anemia. In the aplastic
      anemia trial, 9 out of 12 patients had some improvement when treated with GM-CSF.
      In the Fanconi's anemia trial, 6 of 7 patients showed some improvement when
      treated with GM-CSF. For both groups, improvement in white blood cell count and
      absolute neutrophil count were the most common response. Side effects observed
      during these studies were fever, rash, urticaria, and flu-like symptoms. Nursing
      care of both groups focused on the effects of pancytopenia, as well as the
      potential adverse effects of GM-CSF. Patient education focused on teaching drug
      preparation and storage, subcutaneous injection, and potential side effects.

PMID- 7644283
TI  - Telephone protocols in pediatric ambulatory care.
AB  - Telephone management in pediatric ambulatory care settings is a nursing activity
      that has not been well-defined. The telephone is an vital point of access for
      parents seeking health care advice as well as the nurse in managing common
      childhood illnesses or injuries and providing anticipatory guidance. Literature
      based protocols provide the nurse with intervention resources of current and
      accurate information when advising parents over the telephone. This article
      describes the process of telephone protocol development for responding to parents
      seeking advice at a mid-west tertiary care center.

PMID- 7644284
TI  - Pediatric management problems: cystic fibrosis.

PMID- 7644285
TI  - Varicella zoster vaccine (Varivax).

PMID- 7644286
TI  - Excerpts from family-centered care for children needing specialized health and
      developmental services.
AB  - In 1994, Family-Centered Care for Children Needing Specialized Health and
      Developmental Services was published. This monograph is the third revision of the
      1987 landmark publication titled Family-Centered Care for Children with Special
      Health Care Needs. The revision incorporates several changes: the key elements of
      family-centered care are reworded for clarity; the order in which the elements
      are presented is changed to better illustrate their inter-relationships; new
      understandings about family-centered care are integrated; program examples are
      updated; and research findings are incorporated. The revised key elements of
      family-centered care are listed and described here in material excerpted from the
      1994 monograph.

PMID- 7644287
TI  - The baby K case: ethical challenges of preserving professional integrity.
AB  - Caring for Baby K, an infant born with anencephaly, created moral distress and
      violated the integrity of some nurses. This article explores the nature of
      professional nurses' claims of violations of their integrity, argues for a
      broader moral framework for examining such dilemmas, and suggests strategies for
      addressing these issues in the clinical setting.

PMID- 7644288
TI  - Nursing care of the child with DKA in the PICU.

PMID- 7644289
TI  - Double blind comparison of heparin and saline flush solutions in maintenance of
      peripheral infusion devices.

PMID- 7644290
TI  - Identifying and responding to children's stressful experiences.
AB  - Children's pictorial and verbal descriptions of stressful life events are
      described. Suggestions for recognizing behaviors indicative of children's
      experiences with stressful life experiences and strategies for intervention are
      presented.

PMID- 7644291
TI  - House and Senate budget resolutions for fiscal year 1996: effects on our next
      generation.

PMID- 7644292
TI  - Imaging intracranial tuberculosis in childhood.
AB  - A morphologically based imaging review of intracranial tuberculosis in childhood
      is presented. The computed tomography and magnetic resonance features of
      parenchymal tuberculoma, tuberculous meningitis and meningeal/meniningocerebral
      tuberculoma are illustrated. Recent insight into the nature of tuberculoma
      necrosis and its magnetic resonance correlation is reviewed. Pathogenesis,
      relevant clinical background and the role of modern imaging is discussed.

PMID- 7644294
TI  - Congenital extracranial meningioma.
AB  - The authors report a case of congenital meningioma in a newborn. This tumour is
      extremely rare and only six cases have been reported in the literature. Those
      reported cases were mainly intracranial. This is the first case of a neonatal
      extracranial meningioma that was evaluated preoperatively by computed tomography
      and magnetic resonance imaging.

PMID- 7644293
TI  - Congenital intracranial filariasis: a case report.
AB  - We present the case of a newborn with intracranial extra-axial collections which
      mere partially calcified. The underlying cause was shown to be filariasis which
      had been transmitted from the mother.

PMID- 7644295
TI  - Characterization of superior sagittal sinus blood flow velocity using color flow
      Doppler in neonates and infants.
AB  - The objective of the investigation was to determine what effect intracranial
      pathology has on alterations of superior sagittal sinus blood flow, and to
      determine the role of color flow Doppler imaging of the superior sagittal sinus
      in the diagnosis of intracranial pathology in the neonate and infant. One hundred
      examinations were performed prospectively in 96 patients. The velocity was
      determined with an angle correction at 30-60 degrees and was obtained with and
      without gentle transducer compression. Superior sagittal sinus thrombosis was
      identified in two patients by the absence of flow. Multiple t-tests for
      independent measures showed no clinically significant differences between flow
      velocities with regard to intracranial hemorrhage, ventriculomegaly,
      extracorporeal membrane oxygenation therapy or prematurity. The authors conclude
      that color flow Doppler can accurately diagnose superior sagittal sinus
      thrombosis and may be used to screen high risk neonates such as those with
      thrombosis elsewhere or those treated with extracorporeal membrane oxygenation.
      No clinically significant associations were found between superior sagittal sinus
      flow velocity and any of the parameters evaluated in this study.

PMID- 7644297
TI  - MRI changes in the central nervous system in a child with lupus erythematosus.
AB  - We report on a 10-year-old girl with systemic lupus erythematosus who presented
      in status epilepticus as the only manifestation of central nervous system
      involvement. MRI of the brain showed diffuse gray and white matter lesions which
      almost completely resolved after treatment with methylprednisolone. MRI findings
      in this child are similar to those in adults with diffuse clinical
      manifestations. The study is essential in the initial evaluation of patients
      suspected of central nervous system lupus.

PMID- 7644296
TI  - Cyclosporin A toxicity: MRI appearance of the brain.
AB  - Neurotoxicity is a recognized complication with the use of Cyclosporin A (CSA) in
      bone marrow and organ transplantation patients. Most common symptoms are seizures
      and altered mental status which are usually transient. We report three cases of
      transient neurotoxic episodes in patients receiving CSA after a bone marrow
      transplant. There were reversible low-attenuation changes on CT and bright T2
      weighted signal changes on MRI in the cortex and/or white matter of the cerebral
      hemispheres. All three patients, when given lower maintenance doses of CSA, were
      free of recurrent neurotoxic effects.

PMID- 7644298
TI  - Disc degeneration of pediatric patients in lumbar MRI.
AB  - Magnetic resonance imaging (MRI) is widely used in pediatric spinal disorders,
      but the prevalence of associated lumbar disc degeneration (DD) has not been
      evaluated previously. In this study we investigated whether children with
      suspected spinal disease had increased tendency to early DD. We analyzed lumbar
      MRI scans of 32 patients and 49 control subjects under 15 years old. Only four
      patients (13%) had DD on T2-weighted MRI and they were all over 10 years old.
      Eleven subjects (22%) in the control group had DD. It seems that disc
      degeneration is seldom found in patients under 10 years old.

PMID- 7644299
TI  - Assessment of airways compression by MR imaging in children with aneurysmal
      pulmonary arteries.
AB  - Magnetic resonance imaging (MRI) has an established role in the accurate and non
      invasive assessment of airways compression by congenital vascular rings and
      pulmonary artery slings, making angiography of these lesions unnecessary. This
      role can be broadened to encompass other vascular compressive lesions, as in the
      two pediatric patients described here with aneurysmal pulmonary arteries of
      different etiology, one congenital and the other acquired.

PMID- 7644300
TI  - Systemic arterial collateral esophageal indentations in pseudotruncus arteriosus.
AB  - Barium esophagrams were obtained in two patients with respiratory problems whose
      underlying congenital heart disease was pseudotruncus arteriosus type I. The
      esophagrams revealed vascular indentations on the esophagus, one posteriorly, and
      the other anteriorly. Both types of indentations were secondary to aorto
      pulmonary communicating arteries from the descending aorta.

PMID- 7644301
TI  - Plain-film assessment of the neonate with D-transposition of the great vessels.
AB  - The presenting chest radiographs of 27 new-born patients with D-transposition of
      the great vessels (D-TGV) were evaluated for the degree of pulmonary flow as well
      as other findings classically described in D-TGV (narrow superior mediastinum,
      radiographically absent thymus, inapparent main pulmonary artery, non
      visualization of the malpositioned aortic arch, asymmetric pulmonary blood flow,
      and cardiomegaly). Of the 27 patients, 22 (82%) demonstrated normal or decreased
      flow. The majority of the D-TGV patients also failed to demonstrate any of the
      other classically described radiographic findings. A normal chest radiograph is
      the most common presenting scenario in the neonate with D-TGV.

PMID- 7644302
TI  - Chest radiographs of neonates with respiratory failure caused by congenital
      syphilis.
AB  - Congenital syphilis still occurs in newborn babies and the prevalence has
      increased in recent years, especially in developing countries. This has led to an
      increase in the number of babies with congenital syphilis requiring intensive
      care for respiratory failure. The early recognition of this disease could lead to
      the institution of timely and appropriate treatment. In this study the
      radiological picture of syphilitic pneumonitis is described in 20 neonates
      admitted to our neonatal intensive care unit requiring ventilation for
      respiratory failure. The radiological picture of the babies with syphilis was
      compared to 20 babies with other causes of respiratory distress. The radiological
      picture in 17 babies demonstrated a coarse nodular pattern in addition to band
      like opacities radiating from the hilar regions. The nodular opacities became
      confluent on follow-up radiographs. In 13 cases, the proximal humeri showed
      changes typical of congenital syphilis. Two of the three babies with syphilis who
      did not have the typical chest radiological picture had bony involvement visible
      on the chest radiograph. Both the sensitivity and specificity of radiographic
      diagnosis were 75% with a positive and negative predictive value of 75%. The
      diagnosis of congenital syphilitic pneumonitis can therefore be suspected on
      chest radiographs and should be included in the differential diagnosis of any
      baby who presents with an interstitial pattern on chest radiography.

PMID- 7644303
TI  - Pulmonary aspergillosis and pseudosequestration of the lung in chronic
      granulomatous disease.
AB  - We present a case of chronic granulomatous disease with an angiographically
      proven pseudosequestration of the lung. The patient was a 15-year-old boy who was
      admitted to the hospital with symptoms of fever, cough, hemoptysis and a
      subcutaneous abscess. Aspergillus fumigatus was isolated from the sputum and the
      abscess. During treatment, angiography demonstrated on anomalous blood supply to
      the right middle lobe. The therapeutic implications of pseudosequestration of the
      lung for the treatment of chronic granulomatous disease are discussed.

PMID- 7644304
TI  - Plasma cell granuloma involving the tracheobronchial angle in a child: a case
      report.
AB  - The radiologic findings of plasma cell granuloma involving the left
      tracheobronchial angle in a child are described. The left lung volume was
      decreased on chest radiograph, and CT scan showed an intraluminal mass.

PMID- 7644305
TI  - Cystic intrapulmonary lymphangioma: HRCT findings.
AB  - We report a rare case of cystic intrapulmonary lymphangioma involving the left
      lung, which presented with pneumothorax and respiratory distress in a 6-month-old
      infant. Chest radiographs showed a multicystic lesion in the left lung mimicking
      the features of congenital cystic adenomatoid malformation of the lung. The
      lesion appeared on high-resolution CT (HRCT) as a multiseptate, air-filled cystic
      lesion in the left hilar area. Associated HRCT findings were thickening of
      interlobular septa and bronchovascular bundles in the left lung and the presence
      of peripheral pulmonary vessels within cystic lesions in the apex of the left
      lung. HRCT findings correlated well with histopathologic findings. We suggest
      that these associated findings may be helpful in distinguishing this condition
      from other cystic lung diseases and that this entity should be included in the
      differential diagnosis of multicystic lung lesions.

PMID- 7644306
TI  - Fetal echogenic lung lesions: prenatal ultrasound diagnosis and outcome.
AB  - The differential diagnosis of echogenic areas in the fetal chest include
      congenital diaphragmatic hernia (CDH), cystic adenomatoid malformation (CAM),
      sequestrated lung and tracheal or bronchial atresia. The purpose of this study
      was to evaluate the accuracy of prenatal diagnosis and document outcome in
      fetuses with echogenic chest lesions. Seventeen fetuses with echogenic chest
      masses were seen in our unit between 17 and 36 weeks' gestation over a 5-year
      period. We reviewed these cases retrospectively for prenatal diagnosis, postnatal
      diagnosis and outcome. Prenatal diagnosis was correct in 13 fetuses, with CDH in
      8, sequestrated lung in 4 and tracheal atresia in 1. Four fetuses had incorrect
      or uncertain prenatal diagnoses. In three fetuses CDH and CAM could not be
      differentiated. After delivery two of these had CDH and one had sequestrated
      lung. One fetus with bilateral lesions had prenatal diagnosis of bilateral CAM.
      Post-mortem examination revealed tracheal atresia as part of Fraser syndrome. All
      five babies with sequestrated lung are well and none required surgery. Ten
      fetuses had CDH, two pregnancies were terminated, one died in utero, five died as
      neonates and two babies survived following surgery. The study reveals that in a
      minority of fetuses CDH and CAM could not be differentiated prenatally. We agree
      with recent reports of fetal sequestrated lung describing sonographic improvement
      in utero. A large lesion on initial scan does not necessarily predict a poor
      neonatal outcome in this condition. This, together with the poor outcome in
      fetuses with echogenic CDH and tracheal atresia, has important implications for
      prenatal counselling.

PMID- 7644307
TI  - Hepatic and cerebral infarction in the survivor after the in utero death of a co
      twin: sonographic pattern.
AB  - We report a case of diffuse hepatic and cerebral infarction in a surviving
      preterm co-twin and twin-twin transfusion syndrome studied by ultrasound and
      confirmed by post-mortem examination.

PMID- 7644308
TI  - Imaging evaluation of blunt renal trauma in children: diagnostic accuracy of
      intravenous pyelography and ultrasonography.
AB  - Forty-six consecutive children with blunt renal injury were evaluated
      retrospectively to assess the diagnostic accuracy of the different imaging
      methods, including ultrasonography (US), intravenous pyelography (IVP), and
      computed tomography (CT), and to determine the optimal radiologic management.
      Doppler ultrasonography was never performed in an emergency. Classification of
      the 46 renal injuries was as follows: 25 contusions, 4 lacerations, 11 ruptures,
      and 6 pedicle injuries. The diagnostic accuracy of IVP (80.8%) was superior to
      the diagnostic accuracy of US (41%) in all types of renal injuries. IVP should be
      performed as an emergency procedure when macroscopic hematuria is present, or
      when an isolated renal injury is clinically suspected. Microscopic hematuria
      alone is no longer an indication to perform IVP. Asymptomatic patients with
      microscopic hematuria should have US examination and should be observed with
      performance of serial urine analyses. Multiply injured and hemodynamically stable
      children should be evaluated by contrast-enhanced CT. Hemodynamically unstable
      children should undergo immediate exploratory laparotomy, if it is indicated
      after assessment by imaging.

PMID- 7644309
TI  - Reliability of ultrasound in the early diagnosis of developmental dysplasia of
      the hip.
AB  - The purpose of this study was to determine inter- and intra-observer agreement in
      assessing hip morphology and stability by ultrasound. Three groups of infants, of
      206, 74 and 78 newborns respectively, were examined. Morphology was classified
      into four categories (normal, immature, minor dysplastic and major dysplastic)
      according to subjective assessment, objective measurement (of the acetabular
      inclination angle alpha) or a combination of the two. Inter- and intra-observer
      agreement was determined for reading of recorded ultrasound scans, and for
      examination (recording plus reading of the scans). Hip stability was subjectively
      classified as stable, unstable, dislocatable or dislocated, and inter-observer
      agreement was determined. There was a high degree of agreement for morphological
      classification based on repeated readings of recorded scans by the same observer
      (206 infants, kappa = 0.7 and 0.8 for the two observers, respectively) while the
      degree of agreement between observers was moderate (kappa = 0.5). The agreement
      between observers for repeated readings and recordings was moderate when based on
      a subjective classification (kappa = 0.5). Adding the alpha angle did not improve
      agreement. There was a moderate inter-observer agreement in determining hip
      stability (70 infants, kappa = 0.4). The authors concluded that a high degree of
      inter- and intra-observer agreement in classifying hip morphology may be obtained
      for the reading of recorded ultrasound scans. Inter- and intra-observer agreement
      in producing the scans is poorer than for reading. To obtain a high degree of
      inter-observer agreement in assessing hip morphology and stability in the
      newborn, substantial training, attention to details in the technique, and
      evaluation of results are necessary.

PMID- 7644310
TI  - The role of ultrasound in diagnosis and management of developmental dysplasia of
      the hip.

PMID- 7644311
TI  - CT recognition of spinal epidural air after chest tube placement.
AB  - Intraspinal air has been described in patients undergoing diagnostic lumbar
      puncture and epidural analgesia, as a manifestation of degenerative disk disease,
      and after less common mechanisms, such as blunt trauma [1], strenuous exercise
      [2], and pelvic trauma [3]. We report a case of spinal epidural emphysema
      incidentally noted on CT after placement of a thoracostomy tube.

PMID- 7644312
TI  - A case of an enterorenal fistula and pyelonephritis with air in the renal pelvis.
AB  - We report on a 10-year-old boy with recurrent urinary tract infection. Renal
      ultrasound demonstrated the presence of air in the collecting system of the right
      kidney. The patient was examined radiologically and an enterorenal fistula was
      diagnosed. The case serves as a reminder that, although entero-renal fistulas are
      rare, they should be included in the differential diagnosis of recurrent urinary
      tract infections, especially if air is observed in the collecting system.

PMID- 7644313
TI  - Bochdalek's hernia completely reduced by spontaneous ipsilateral tension
      pneumothorax.
AB  - This report describes a premature (29 weeks gestation) infant with a left
      Bochdalek's diaphragmatic hernia, in whom the development of a spontaneous
      ipsilateral tension pneumothorax caused complete reduction of the hernia into the
      abdomen. In the presence of a tension pneumothorax, a diaphragmatic hernia may be
      masked on a chest radiograph and therefore difficult to diagnose.

PMID- 7644314
TI  - Ulnar club-hand and constriction-ring syndrome.
AB  - An infant presented with ulnar club hand and constriction ring syndrome involving
      all four limbs. The former abnormality was diagnosed by ultrasound at 23 weeks
      gestation. This association has not been previously described.

PMID- 7644315
TI  - MR imaging of a subglottic hemangioma.

PMID- 7644316
TI  - Pulmonary Gaucher's disease: high-resolution computed tomographic features.
AB  - CT findings in pulmonary Gaucher's disease have not been previously reported.
      Chest radiograph of a patient with pulmonary involvement in type I Gaucher's
      disease proven by biopsy showed linear and reticulo-nodular opacities. High
      resolution CT demonstrated thickening of the interlobular septa and between four
      and six small nodules within secondary lobules, probably each corresponding to an
      acinus.

PMID- 7644317
TI  - The use of CT and MR in the management of advanced spinal tuberculosis.

PMID- 7644319
TI  - Attention capture by contour onsets and offsets: no special role for onsets.
AB  - In five experiments, we investigated the power of targets defined by the onset or
      offset of one of an object's parts (contour onsets and offsets) either to guide
      or to capture visual attention. In Experiment 1, search for a single contour
      onset target was compared with search for a single contour offset target against
      a static background of distractors; no difference was found between the
      efficiency with which each could be detected. In Experiment 2, onsets and offsets
      were compared for automatic attention capture, when both occurred simultaneously.
      Unlike in previous studies, the effects of overall luminance change, new-object
      creation, and number of onset and offset items were controlled. It was found that
      contour onset and offset items captured attention equally well. However, display
      size effects on both target types were also apparent. Such effects may have been
      due to competition for selection between multiple onset and offset stimuli. In
      Experiments 3 and 4, single onset and offset stimuli were presented
      simultaneously and pitted directly against one another among a background of
      static distractors. In Experiment 3, we examined "guided search," for a target
      that was formed either from an onset or from an offset among static items. In
      Experiment 4, the onsets and offsets were uncorrelated with the target location.
      Similar results occurred in both experiments: target onsets and offsets were
      detected more efficiently than static stimuli which needed serial search; there
      remained effects of display size on performance; but there was still no advantage
      for onsets. In Experiment 5, we examined automatic attention capture by single
      onset and offset stimuli presented individually among static distractors. Again,
      there was no advantage for onset over offset targets and a display size effect
      was also present. These results suggest that, both in isolation and in
      competition, onsets that do not form new objects neither guide nor gain automatic
      attention more efficiently than offsets. In addition, in contrast to previous
      studies in which onsets formed new objects, contour onsets and offsets did not
      reliably capture attention automatically.

PMID- 7644318
TI  - Inflammatory pseudotumour of the lung.

PMID- 7644320
TI  - Modality dependency of familiarity ratings of Japanese words.
AB  - Familiarity ratings for a large number of aurally and visually presented Japanese
      words wer measured for 11 subjects, in order to investigate the modality
      dependency of familiarity. The correlation coefficient between auditory and
      visual ratings was .808, which is lower than that observed for English words,
      suggesting that a substantial portion of the mental lexicon is modality
      dependent. It was shown that the modality dependency is greater for low
      familiarity words than it is for medium- or high-familiarity words. This
      difference between the low- and the medium- or high-familiarity words has a
      relationship to orthography. That is, the dependency is larger in words
      consisting only of kanji, which may have multiple pronunciations and usually
      represent meaning, than it is in words consisting only of hiragana or katakana,
      which have a single pronunciation and usually do not represent meaning. These
      results indicate that the idiosyncratic characteristics of Japanese orthography
      contribute to the modality dependency.

PMID- 7644321
TI  - Influence of flicker on perceived size and depth.
AB  - Previous research (e.g., Wong & Weisstein, 1984a, 1985) has shown that flickering
      stimuli appear to be more distant than nonflickering stimuli at the same physical
      distance. Given this relation between flicker and perceived depth, inappropriate
      constancy scaling theories predict that flickering stimuli should be perceived as
      larger than nonflickering ones. In contrast, links between flicker and motion
      perception suggest that flickering stimuli should be perceived as smaller than
      nonflickering ones. Two experiments tested these contrasting predictions. In
      Experiment 1, 22 subjects compared flickering and nonflickering vertical lines
      and reported that the flickering stimulus appeared significantly smaller than the
      nonflickering one. In Experiment 2, 21 subjects reported that the stimuli used in
      Experiment 1 produced depth effects similar to those reported in previous
      experiments: flickering stimuli were perceived as more distant than nonflickering
      ones. The observed effect of flicker on perceived size was contrary to
      predictions from inappropriate constancy scaling theory, but consistent with
      views that motion and flicker are processed by the same pathway.

PMID- 7644322
TI  - An examination of attentional control in the auditory modality: further evidence
      for auditory orienting.
AB  - Four experiments are reported that examine attentional control in the auditory
      modality. In Experiment 1, the subjects made detection responses to the onset of
      a monaurally presented pure tone that was preceded by a pure-tone cue. On a valid
      trial, the cue was presented in the same ear as the target; on an invalid trial,
      it was presented in the contralateral ear to the target; and on a neutral trial,
      it was presented in both ears. Overall performance was facilitated on valid
      trials in comparison with invalid trials. In later experiments, the subjects made
      choice decisions about the location of the target, and significant cuing effects
      were found relative to the neutral condition. Finally, performance was assessed
      in the presence of central (spoken) word cues. Here, the content of the cue
      specified the likely location of the target. Under these conditions, costs and
      benefits were found over a range of cue-target stimulus onset asynchronies. The
      results are discussed in terms of automatic and controlled attentional processes.

PMID- 7644323
TI  - The perception of surface orientation from multiple sources of optical
      information.
AB  - An orientation matching task was used to evaluate observers' sensitivity to local
      surface orientation at designated probe points on randomly shaped 3-D objects
      that were optically defined by texture, lambertian shading, or specular
      highlights. These surfaces could be stationary or in motion, and they could be
      viewed either monocularly or stereoscopically, in all possible combinations. It
      was found that the deformations of shading and/or highlights (either over time or
      between the two eyes' views) produced levels of performance similar to those
      obtained for the optical deformations of textured surfaces. These findings
      suggest that the human visual system utilizes a much richer array of optical
      information to support its perception of shape than is typically appreciated.

PMID- 7644324
TI  - Abrupt luminance change pops out; abrupt color change does not.
AB  - The present studies investigated whether an isoluminant color change pops out,
      indicating that it can be detected preattentively in parallel. The results of
      Experiment 1 show that an abrupt color change presented on an equiluminant
      background does not pop out. However, when the color change is accompanied by a
      small luminance change, it does pop out. The results of Experiment 2 show that
      the pop-out is fully due to the luminance change and not to the color change. The
      results of Experiments 3 and 4 show that the failure to find a pop-out at
      equiluminance cannot be attributed to the limited temporal resolution for
      chromatic stimuli. The results of Experiment 5 show that particular search
      strategies cannot be responsible for the obtained results. The results are in
      agreement with physiological findings regarding the parvo and magno systems.

PMID- 7644325
TI  - Extraction of relief from visual motion.
AB  - We quantified the ability of human subjects to discriminate the relative distance
      of two points from a slanted plane when viewing the projected velocities of this
      scene (orthographic projection). The relative distance from a plane (called
      relief) is a 3-D property that is invariant under linear (affine)
      transformations. As such, relief can in principle be extracted from the
      instantaneous projected velocity field; a metric representation, which requires
      the extraction of visual acceleration, is not required. The stimulus consisted of
      a slanted plane P (specified by three points) and two points Q1 and Q2 that are
      non-coplanar with P. This configuration of points oscillated rigidly around the
      vertical axis. We have measured the systematic error and accuracy with which
      human subjects estimate the relative distance of points Q1 and Q2 from plane P as
      a function of the slant of P. The systematic error varies with slant: it is low
      for small slant values, reaches a maximum for medium slant values, and drops
      again for high slant values. The accuracy covaries with the systematic error and
      is thus high for small and large slant values and low for medium slant values.
      These results are successfully modeled by a simple relief-from-motion computation
      based on local estimates of projected velocities. The data are well predicted by
      assuming (1) a measurement error in velocity estimation that varies
      proportionally to velocity (Weber's law) and (2) an eccentricity-dependent
      underestimation of velocity.

PMID- 7644326
TI  - Effect of stimulus repetition on positive and negative identity priming.
AB  - Most negative-priming experiments have used a limited number of stimuli that are
      repeated many times throughout the experiment. We report five experiments that
      examine in greater detail the role of stimulus repetition in negative priming.
      Subjects were presented with displays consisting of two or more words, and were
      required to name the word printed in red. On attended repetition (AR) trials, the
      target word was the same as the target word on the preceding trial. On ignored
      repetition (IR) trials, the target word was the same as the distractor word on
      the preceding trial. Experiments 1 and 2 used novel words, and obtained positive
      priming on AR trials, but no negative priming on IR trials. Experiments 3 and 4
      used repeated words, and obtained negative priming on IR trials, but no positive
      priming on AR trials. In Experiment 5, both novel and repeated words were
      intermixed, and negative priming was observed for repeated, but not novel, IR
      conditions, whereas positive priming was observed for novel, but not repeated, AR
      conditions. Together, Experiments 1-5 demonstrate that positive and negative
      identity priming are modulated by stimulus repetition and are stimulus specific.

PMID- 7644327
TI  - The effect of combinations of image degradations in a discrimination task.
AB  - This paper explores the ways in which combinations of image degradations affect
      discrimination. Nine experiments are described that examine the discriminability
      of visual images that are degraded with three types of information reducing
      transformations: random punctate visual interference, low-pass spatial frequency
      filtering, and local area (i.e., block) averaging. The results of these
      experiments characterize a powerful visual ability to discriminate highly
      degraded stimuli unless that ability is severely challenged by relatively high
      levels of random visual interference. Discriminative commutativity of the orders
      in which the other two degradations are imposed is demonstrated. That is, the
      order in which the degradations are applied does not affect the final
      discriminative outcome. This result is in contrast to predictions from relevant
      mathematics and direct examination of the images produced by both orders of
      degradation. The commutativity is attributed to the particularly strong effect of
      the low-pass spatial frequency filtering degradation on the discrimination
      process. This study also demonstrates that combinations of degradations in a
      discrimination task always result in a reduction in performance, and never in the
      improvement that has been reported for recognition. This difference is attributed
      to the fact that form discrimination is mediated mainly by local features and
      high-frequency spatial components, whereas recognition is mediated mainly by
      global features and low-frequency spatial components.

PMID- 7644328
TI  - Combining image degradations in a recognition task.
AB  - Six experiments are reported that investigate the effect on form recognition
      performance of combining three kinds of stimulus degradations: local area
      averaging of intensities, low-pass spatial frequency filtering, and random dot
      visual interference. The effects are shown to be more complicated than previously
      reported in simple demonstrations. The complexity of the results suggests that
      models based on single stimulus attributes such as energy or spatial frequency
      spectrum probably cannot account for the data. Eclectic theories that invoke
      combinations of redundant processes may be necessary for describing visual
      recognition phenomena, even within the limited domain examined in this study.

PMID- 7644329
TI  - 3-D shape perception.
AB  - In this paper, we analyze and test three theories of 3-D shape perception: (1)
      Helmholtizian theory, which assumes that perception of the shape of an object
      involves reconstructing Euclidean structure of the object (up to size scaling)
      from the object's retinal image after taking into account the object's
      orientation relative to the observer, (2) Gibsonian theory, which assumes that
      shape perception involves invariants (projective or affine) computed directly
      from the object's retinal image, and (3) perspective invariants theory, which
      assumes that shape perception involves a new kind of invariants of perspective
      transformation. Predictions of these three theories were tested in four
      experiments. In the first experiment, we showed that reliable discrimination
      between a perspective and nonperspective image of a random polygon is possible
      even when information only about the contour of the image is present. In the
      second experiment, we showed that discrimination performance did not benefit from
      the presence of a textured surface, providing information about the 3-D
      orientation of the polygon, and that the subjects could not reliably discriminate
      between the 3-D orientation of textured surface and that of a shape. In the third
      experiment, we compared discrimination for solid shapes that either had flat
      contours (cuboids) or did not have visible flat contours (cylinders). The
      discrimination was very reliable in the case of cuboids but not in the case of
      cylinders. In the fourth experiment, we tested the effectiveness of planar motion
      in perception of distances and showed that the discrimination threshold was large
      and similar to thresholds when other cues to 3-D orientation were used. All these
      results support perspective invariants as a model of 3-D shape perception.

PMID- 7644330
TI  - Negative priming depends on ease of selection.
AB  - Negative priming effects have been offered as evidence that distractor stimuli
      are identified. We conducted two experiments to determine if such effects occur
      even when it is easy to discriminate target from distractor stimuli. In
      Experiment 1, we found the usual negative priming effect when target and
      distractor positions varied from trial to trail, but not when these positions
      remained fixed. Experiment 2 extended these results to a situation where the ease
      of selection varied only in the prime display. These findings argue that
      irrelevant inputs can be filtered out prior to stimulus identification under
      certain circumstances and therefore pose problems for strict late selection
      theories.

PMID- 7644331
TI  - Vibrotactile pattern discrimination and communality at several body sites.
AB  - In a series of experiments, the effects of spatial layout on vibrotactile pattern
      perception were explored by testing the ability to discriminate between two
      sequentially presented patterns that share active elements in the same spatial
      locations. Two-dimensional displays were used in order to examine the functional
      relationship between discrimination performance and pattern communality, defined
      as the sharing elements, on different body sites. Accuracy of discrimination
      judgments was inversely proportional to communality, regardless of the number of
      pattern elements. For compact arrays fitted to the finger, palm, and thigh, the
      effects of communality appeared equivalent. The similarity between finger and
      thigh functions is remarkable, considering the dramatic differences between these
      sites in receptor components and structure. When these data were compared with
      those from arrays with distributed contactors, performance was substantially
      better with well-separated pattern elements. Such findings help to explicate how
      information from apposed patterns can best be delivered to the skin through
      tactile communication systems.

PMID- 7644332
TI  - Directional sensitivity to a tactile point stimulus moving across the fingerpad.
AB  - The ability of subjects to discriminate between directions of a point contact
      moving across the fingerpad was examined. Subjects were required to report, using
      an adaptive two-interval, two-alternative forced-choice procedure, whether in two
      sequential stimuli the direction of motion changed in a clockwise or
      counterclockwise direction. The overall mean orientation-change threshold across
      eight stimulus orientations was approximately 14 degrees, with the lowest
      threshold for the point motion toward the wrist. This observed lower threshold in
      the distal-to-proximal direction is thought to be due to stretching of the skin
      at the tip of the fingernail, to which one may be particularly sensitive. For all
      orientations, thresholds were generally more uniform and higher than those
      reported on vibrotactile linear contactor arrays for horizontal and vertical
      orientations.

PMID- 7644333
TI  - [Contrast enhancement and morphological findings of hematopoietic regions of bone
      marrow on MR imaging: comparative study with spondylitis and vertebral tumors].
AB  - The enhanced MR findings of hematopoietic regions in aplastic anemia were
      compared with those of spondylitis, metastatic vertebral tumors and hematologic
      neoplasms. The enhanced MR images showed hematopoietic regions to homogeneously
      enhance and occupy the margin of vertebral bodies, while spondylitis and
      metastatic tumors appeared as round, inhomogeneously enhancing lesions. MR images
      of leukemia and myelodysplastic syndrome showed homogeneous enhancement at the
      margins of vertebrae that was difficult to differentiate from hematopoietic
      regions. Enhanced MR images were useful in detecting the hematopoietic areas in
      marrow and differentiating them from spondylitis and metastatic tumors, although
      further experience is needed to distinguish between tumorous hyperplastic regions
      and benign hematopoietic regions in marrow.

PMID- 7644334
TI  - [MR imaging of temporomandibular joint (TMJ): mandibular fracture and traumatic
      disk injury].
AB  - Using an 1.5 Tesla superconducting MR unit and surface coil, 12 mandibular
      fracture patients were evaluated for TMJ disk change. Sagittal and coronal images
      of the TMJ with a slice thickness of 2mm were obtained with FISP 2D or 3D. TR =
      30 msec, TE = 12 msec, and flip angle = 40 degrees were applied. Among 12
      patients, FISP 3D revealed increased signal intensity of the disk in 70% of
      cases. Traumatic fluid collection at or adjacent to the TMJ showed high
      intensity. The disk was displaced anteromedially regardless of the site of
      fracture.

PMID- 7644335
TI  - [CT findings of pancreatic carcinoma: evaluation with the combined method of
      early enhancement CT and high dose enhancement CT].
AB  - Computed tomographic (CT) findings of pancreatic ductal adenocarcinoma were
      studied with the combined method of early enhancement CT and high dose
      enhancement CT in 72 carcinomas. Common Findings were change in pancreatic
      contour, abnormal attenuation in a tumor and dilatation of the main pancreatic
      duct. The incidence of abnormal attenuation and dilatation of the main pancreatic
      duct and bile duct was constant regardless of tumor size. The finding of
      hypoattenuation at early enhancement CT was most useful for demonstrating a
      carcinoma. However, this finding was negative in ten cases, five of which showed
      inhomogenous hyperattenuation at high dose enhancement CT. The detection of
      change in pancreatic contour and dilatation of the main pancreatic duct was most
      frequent at high dose enhancement CT. The finding of change in pancreatic contour
      and/or abnormal attenuation in a tumor could be detected in 47 cases at plain CT,
      66 at early enhancement CT and 65 at high dose enhancement CT. Since the four
      cases in which neither finding was detected by any CT method showed dilatated
      main pancreatic duct, there was no case without abnormal CT finding. This
      combined CT method will be a reliable diagnostic technique in the imaging of
      pancreatic carcinoma.

PMID- 7644336
TI  - [Intravenous MR arthrography of the knee].
AB  - A study was undertaken to determine whether or not intravenous MR arthrography
      can be used in clinical practice. Forty patients with internal derangement of the
      knee (11-68 years old) were imaged with MRI before and after intravenous
      injection of Gd-DTPA. In all knees there was enhancement of joint fluid,
      regardless of the amount of fluid. The peak enhancement of joint fluid was
      reached at 30 minutes after the administration of the contrast agent. The
      contrast between joint fluid and meniscus/cartilage was higher in MR arthrography
      than in proton density images. There was an increase in contrast between grade
      III lesions in the meniscus and intact meniscus on MR arthrography. It was
      concluded that intravenous MR arthrography can be a useful alternative to intra
      articular arthrography.

PMID- 7644337
TI  - [Complications of percutaneous transluminal angioplasty].
AB  - Four hundred twenty-three percutaneous transluminal angioplasties with 383
      percutaneous arterial punctures in 346 patients were reviewed to determine the
      frequency, distribution and causes of complications. Complications were seen at
      the angioplasty site and puncture site along with miscellaneous complications,
      the incidence rates being 9.5% (40 of 423 PTAs), 11.7% (45 of 383 punctures), and
      2.0% (7 of 346 patients), respectively. Major complications occurred in 20 cases,
      and surgical procedures were required in six cases. Mortality as a complication
      of PTA was not seen. Angioplasty site complications included 13 spasms, eight
      dissections, five thromboses, 13 distal embolizations and one perforation. Most
      puncture site complications were benign hematomas, but there were other types
      such as a pseudoaneurysm requiring bypass grafting, a thrombosis requiring
      thrombolysis and a large quantity of bleeding requiring transfusion. The
      incidence of angioplasty site complications was significantly higher (p < 0.01)
      in the procedure for complete occlusion than that for stenosis. The puncture site
      and miscellaneous complications were also more frequent in complete occlusions.
      The incidence of complications increased with age, although this tendency did not
      reach statistical significance.

PMID- 7644338
TI  - [MR imaging features of chronically torn anterior cruciate ligament].
AB  - Magnetic resonance (MR) images of 40 knee joints with arthroscopically proved
      chronic anterior cruciate ligament (ACL) tears were retrospectively evaluated.
      MRI demonstrated various features of chronic ACL tears: 19 knees revealed with no
      identifiable ligamentous structure, and 21 had residual ligamentous structures.
      These pseudoligaments, 14 discontinuous bands and seven continuous bands with
      elongation, were residual torn ligamentous fibers and/or synovial tissues. All
      the discontinuous bands were disrupted from the femoral attachment and were
      likely to traverse the lower intercondylar space. Six disrupted ligaments were
      attached to the lateral aspect of the posterior cruciate ligament (PCL). Coronal
      T2-weighted gradient echo images showed better delineation of the disrupted
      femoral attachment and adhesion to the PCL. A chronic ACL tear with minimal
      elongation or with PCL attachment at a higher position may occasionally be
      difficult to distinguish from an intact ligament.

PMID- 7644339
TI  - [Radiological and anatomical investigation of calcific tendinitis of the gluteus
      maximus tendon].
AB  - The radiological findings in four cases of gluteus maximus tendinitis were
      retrospectively analyzed. All the patients underwent radiographic, CT and MRI
      examinations. Amorphous or round calcifications were detected on lateral
      radiographs in three cases, and on CT in all cases. A small cortical erosion was
      observed in three cases on both radiographs and CT. MRI showed a thickened
      gluteus maximus tendon, but no other specific features. In the supine position,
      which is common in routine CT and MRI studies, the calcific deposits appeared to
      be distributed along the vastus lateralis muscle tendon. To correlate these
      radiographic observations with the topographic anatomy of the tendon's insertion,
      we investigated 14 thighs of seven cadavers, and clarified that the tendon's
      insertion was the main component of the lateral femoral intermuscular septum.
      Consequently we performed MRI on a volunteer in a prone position who was asked to
      maintain contraction of the gluteus maximus and quadratus femoris muscles. The
      images obtained showed clearly that the gluteus maximus tendon was directed
      dorsally. In conclusion, radiography and CT are the modalities of choice for
      diagnosis of this entity. Additionally, radiologists should be aware that the
      gluteus maximus tendons are directed laterally as a main part of the lateral
      femoral intermuscular septum on routine CT and MRI.

PMID- 7644340
TI  - Intraoral MR lymphography: a new method for selective enhanced detection of the
      cervical lymph nodes.

PMID- 7644341
TI  - [Differential diagnosis of solitary pulmonary nodules by computerized statistical
      analysis using CT number].
AB  - There have been previous reports on the differentiation of benign pulmonary
      nodules from malignant ones using CT number. However, most of the nodules were
      without calcification, and diagnosis could be made only in limited cases. In the
      present study we established new multiple variables such as relative high density
      over the 75th percentile, inner gradient number (inner irregular rate), edge
      gradient number (edge irregular rate) and increased area rate (IAR). They are
      automatically calculated from CT data by computer. These variables are
      transformed into relative values, enabling comparisons of nodules without a
      standard reference phantom. With IAR, pulmonary nodules were classified into
      three types: type 1 (IAR 1.0-1.4), a high-density solid mass with well-defined
      margin; type 2 (IAR 1.4-2.0) between type 1 and type 3; and type 3 (IAR > 2.0) a
      low-density infiltrated mass with ill-defined margin. We studied 52 cases with
      solitary pulmonary nodules, whose diagnoses were confirmed either histologically
      or on follow-up. There were 34 benign nodules and 18 primary lung cancers. Using
      step-wise multiple regression with three variables, 42 of 52 cases were correctly
      diagnosed. Twenty-four of 28 type 1 cases and all 14 of type 2 cases were
      correctly diagnosed. This computer analysis is considered to be useful in
      distinguishing between benign and malignant solitary pulmonary nodules.

PMID- 7644342
TI  - [Evaluation of compression radiotherapy in pelvic treatment].
AB  - In pelvic irradiation, the volume of irradiated small intestine is one of the
      major factors responsible for both acute and late gastrointestinal complications.
      In this study, exclusion of the small intestine from the pelvic radiation field
      was attempted with lower abdominal wall compression and bladder distention in the
      prone position. The mobility of intrapelvic and several problems associated with
      this technique were investigated. In our results, the small intestine was
      effectively moved outside of the whole pelvic radiation field in all but two
      patients. Treatment interruption of 2 days was observed in only two patients.
      With the AP/PA opposing field method the abdominal skin dose near the compression
      pillow was revealed to be higher and the dose at the isocenter was inhomogeneous;
      thus, a three- or four-field technique is recommended if abdominal wall
      compression is used.

PMID- 7644343
TI  - [Determination of source position for four radiography systems with orthogonal
      projections in brachytherapy].
AB  - Four configurations of two X-ray tube positions are available for determining the
      position of a point using two orthogonal films. For each configuration, there are
      many formulas for calculating the coordinate of a point: the least squares
      methods with and without physical meaning, such as six sets of geometrical
      solutions, an approximation method with constant magnifications and so on. It is
      troublesome for a person in charge of treatment planning to directly derive a
      formula or select an appropriate formula from numerous ones for the four
      configurations. Thus, a method to easily apply the published formula for a
      configuration to the other three configurations is described in simulations and a
      clinical case using rotation matrixes of the right-handed coordinate system. Each
      diagonal element of the rotation matrixes is 1 or -1, and the other elements are
      0.

PMID- 7644345
TI  - Survey cites need for HIV/AIDS education in long term care.

PMID- 7644344
TI  - [MR angiography of the venous system of lower extremities with gadolinium
      enhanced fast spoiled GRASS].
AB  - MR angiography (MRA) of the venous system of the lower extremities was carried
      out in 10 patients with varicose veins using the Gd-DTPA-enhanced Fast Spoiled
      GRASS (FSPGR) method. The quality of imaging of the popliteal vein (n = 20), calf
      deep vein (n = 20), varicose vein (n = 12), and femoral vein (n = 6) were
      assessed in terms of four categories: excellent, good, marginally adequate and
      nondiagnostic. Nineteen popliteal veins, seventeen calf deep veins, and nine
      varicose veins were judged as excellent or good. All femoral veins were evaluated
      as excellent. Enhanced FSPGR was useful for the preoperative evaluation of
      patients with varicose veins.

PMID- 7644346
TI  - NJSNA Position Statement. Disclosure of HIV positive health care workers.

PMID- 7644347
TI  - Any willing provider.

PMID- 7644348
TI  - Tort reform in New Jersey.

PMID- 7644349
TI  - Plasma interacts with mafosfamide toxicity to normal haematopoietic progenitor
      cells: impact on in vitro marrow purging.
AB  - Bone marrow purging with cyclophosphamide derivatives in autologous bone marrow
      transplantation has demonstrated that the killing of leukemic cells and
      simultaneous preservation of normal progenitor cells depends on a number of
      parameters, in particular the haematocrit, nucleated cell concentration and
      nature of the cells. We have previously described a reliable experimental
      procedure for in vitro bone marrow treatment, based on individual adjustment of
      the drug dosage. The present study reveals an inhibitory action of plasma on the
      toxicity of mafosfamide to normal haematopoietic progenitor cells. In an initial
      series of 42 successive patients, determination of the CFU-GM lethal dose 95%
      (CFU-GM LD 95) showed this parameter to be inversely correlated to the nucleated
      cell concentration (NCC) (p < 0.001). Assuming the plasma content of the buffy
      coat cells (BC) to be higher in the less rich marrow samples, we then
      investigated the role of plasma in progenitor cell sensitivity to the drug.
      Results were as follows: (1) in the presence of 60% autologous or allogeneic
      plasma, CFU-GM LD 95 was increased by a factor of 2.18 +/- 0.35 or 1.98 +/- 0.23
      respectively as compared to controls in a solution of 2% bovine serum albumin (p
      = 0.014), (2) this observation remained valid whatever the origin of the plasma
      and (3) the same was true whatever the nature of the cells, derived from normal
      donors or patients with haematological malignancies. These data suggest that
      plasma contains an inhibitor(s) of mafosfamide.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7644350
TI  - Characterization of factor VIII gene inversions using a non-radioactive detection
      method: a survey of 102 unrelated haemophilia A families from northern France.
AB  - Intrachromosomal rearrangements of the long arm of chromosome X, between gene A
      (F8A) in intron 22 of the factor VIII gene and one of its two telomeric copies,
      are responsible for about half of the severe cases of haemophilia A. A group of
      98 unrelated patients from Northern France with moderate to severe haemophilia A
      was screened for this gene inversion using a non-radioactive Southern blotting
      method. Whereas none of the 18 moderately affected patients presented the FVIII
      gene rearrangement, gene inversion was found in 38 (48%) of the 80 severe
      haemophilia A patients. Recombinations involving the distal copy of gene A (group
      1) were more frequent (79%) than those involving the proximal copy (group 2).
      Individual variation in the number of gene A copies on the X chromosome probably
      explains an alternative Southern blot profile, referred to as group 3 inversion,
      which was observed in one of our patients. In the severely affected patients,
      neither the prevalence of inhibitor development nor the frequency of sporadic
      cases differed significantly in the group presenting gene inversion as compared
      to the group without chromosomal rearrangement. Study of four families where no
      patient was available enabled in one case direct carrier detection and prenatal
      diagnosis in the absence of an affected member. The Southern blotting technique
      described in the present work is relevant to about 50% of cases of severe
      haemophilia A, can be performed without use of a radiolabelled probe and
      represents a major advance in the diagnosis of the disease.

PMID- 7644351
TI  - Thrombomodulin and von Willebrand factor in smokers and during smoking.
AB  - Circulating thrombomodulin (TM) and von Willebrand factor (vWF) were determined
      in smokers before and after smoking of two filter cigarettes and in control
      subjects. The basal levels of TM and vWF were significantly increased in smokers
      relative to controls (p < 0.001). However, levels of these two factors remained
      unchanged immediately after smoking of two filter cigarettes, while a
      statistically significant correlation was observed only between plasma TM and
      number of years of smoking (p < 0.05).

PMID- 7644352
TI  - Study of the vesicles released during conservation of red cells.
AB  - The purpose of this study was to determine the protein composition of the
      vesicles released from senescent erythrocytes and its variation during their
      experimental conservation at +4 degrees C in citrate phosphate dextrose (CPD),
      over a period of 8 weeks. Techniques employed included electron microscopy, SDS
      PAGE and immunoblotting. Electron microscopic observation of senescent
      erythrocytes showed the simultaneous release of one or several vesicles of
      varying size and shape, while close examination of individual vesicles revealed a
      slack membrane structure and the presence of band 3 protein. SDS-PAGE and
      immunoblotting showed the vesicles to be composed mainly of band 3 and its
      breakdown products and to be lacking in spectrin. Use of specific antibodies
      demonstrated the presence of free haemoglobin, immunoglobulin G (IgG) and
      fragment C3b of complement. During conservation for 8 weeks, the concentration of
      band 3 protein decreased, while the concentrations of IgG and C3b increased and
      there was no apparent variation in haemoglobin levels.

PMID- 7644353
TI  - Tuberculosis associated haemophagocytic syndrome: two cases with a favourable
      outcome.
AB  - Haemophagocytic syndrome is a heterogenous disease characterized by disordered
      macrophage activation associated with viral, bacterial or parasitic infection.
      The few reports of haemophagocytosis occurring in the presence of mycobacterial
      infection show a high mortality rate and we present two further cases notable for
      their favourable issue. Rapidity of diagnosis and immediate treatment could
      explain the avoidance of a fatal outcome.

PMID- 7644354
TI  - Infrequent sites of extramedullary relapse after allogeneic bone marrow
      transplantation.
AB  - In the present report, we describe two cases of rare extramedullary relapse
      (skin, muscle) after allogeneic bone marrow transplantation (BMT). As both
      patients were male and had received sex mismatched (non T-depleted) BMT, marrow
      samples were analysed with a Y-chromosome specific probe allowing the sensitive
      detection of host DNA. The proportion of host DNA remained low in all post BMT
      samples from these patients, even at the time of extramedullary relapse.

PMID- 7644355
TI  - Multiple myeloma with bone marrow biopsy features simulating concomitant chronic
      idiopathic myelofibrosis.
AB  - Multiple myelomas occasionally exhibit bone marrow lesions simulating a
      concomitant chronic idiopathic myelofibrosis. In the present study, trephine
      biopsy histologies of such "myelofibrotic" myelomas are described and compared to
      those from a case of true chronic idiopathic myelofibrosis which developed in the
      course of chronic lymphocytic leukaemia. "Myelofibrotic" myeloma are
      characterized by osteosclerosis, marrow fibrosis and focal megakaryocytic
      hyperplasia in the presence of plasma cell infiltration of the bone marrow. These
      myelomas are to be distinguished from the more commonly occurring multiple
      myeloma with simple marrow fibrosis and/or osteosclerosis. Furthermore,
      "myelofibrotic" myelomas are not identical to myelomas coexisting with true
      chronic idiopathic myelofibrosis, a condition which would appear to be extremely
      rare and should only be diagnosed if focal megakaryocytic hyperplasia with atypia
      can be unequivocally demonstrated. Avoidance of misinterpretation of
      "myelofibrotic" myeloma requires a knowledge of these different myeloma variants.

PMID- 7644356
TI  - Acquired circulating anticoagulant with anti-factor V activity in AIDS: first
      case report.
AB  - An acquired circulating anticoagulant with anti-factor V activity appeared in a
      29 year old AIDS patient with widespread Kaposi's sarcoma following 21 days of
      fresh frozen plasma therapy for haemolytic and uraemic syndrome. Residual factor
      V activity was very low (< 5% of normal). However, the inhibitor was of low titre
      (0.5 Bethesda Units/ml), while antigenic factor V levels remained at 100%. Dot
      blotting with human factor V and polyvalent and specific immunoglobulin antisera
      showed the antibody to belong to the IgG class. Haemostatic tests in vitro were
      only partly corrected by addition of washed human platelets and despite
      transfusion of large amounts of platelets the patient died from massive pulmonary
      haemorrhage. This would appear to be the first documented case of an anti-factor
      V inhibitor occurring in an AIDS patient.

PMID- 7644357
TI  - Circulating endothelial markers and ischemic status in peripheral occlusive
      arterial disease.
AB  - In 34 patients with peripheral occlusive arterial disease, circulating levels of
      endothelial cell markers were compared with the ischemic status. Unlike tissue
      plasminogen activator and plasminogen activator inhibitor, plasma levels of
      thrombomodulin were closely related to both transcutaneous oxygen pressure (p =
      0.01) and the graded clinical stages of disease (p = 0.02). Levels of von
      Willebrand factor were correlated only with the transcutaneous oxygen pressure (p
      = 0.04). Since thrombomodulin and von Willebrand factor constitute markers of
      endothelial cell damage, the extent of endothelial injury would appear to be
      determined by the ischemic status.

PMID- 7644358
TI  - The frequency of the factor V gene R506Q mutation varies between regions of
      France.

PMID- 7644359
TI  - Unimpressive stuff.

PMID- 7644360
TI  - Shadow boxing. Interview by David Payne.

PMID- 7644363
TI  - Protection package.

PMID- 7644362
TI  - The end of the line.

PMID- 7644361
TI  - Poor prognosis.

PMID- 7644364
TI  - Nurse practitioners. A natural extension?

PMID- 7644365
TI  - Nurse practitioners. A unique service?

PMID- 7644366
TI  - Going it alone.

PMID- 7644367
TI  - Improving care for children in a multi-agency alliance.
AB  - The impact of asthma on morbidity and mortality is well documented. This paper
      describes the work of a healthy alliance comprising multi-agency representatives
      from primary and secondary care in their quest to improve the quality of care for
      children with asthma.

PMID- 7644368
TI  - Changing the nursing culture in a special hospital.
AB  - In August 1992 a damning report was published on the mental health services
      provided at Ashworth Special Hospital in Merseyside. It described a brutalising
      and damaging regime in which nurses were singled out for the strongest criticism.
      In November 1994 the Health Advisory Service (HAS), which has a watchdog role,
      spent three weeks at Ashworth reviewing developments in the wake of the inquiry
      report. The HAS report, published last March, praised the hospital for undergoing
      tremendous change and recovery. Areas of exemplary practice were evident and
      major dehumanising practices had been eliminated. This paper attempts to analyse
      some of the difficulties confronting nurses at the hospital during the years of
      change between the public inquiry and the HAS visit, and identifies recent major
      achievements and areas for further work.

PMID- 7644369
TI  - A comparative study of depot injection techniques.
AB  - Depot injections of long-acting neuroleptic drugs, by maintaining a consistent
      drug regime, together with regular contact with health-care professionals, are an
      important factor in helping psychiatric patients who live in the community. As
      these injections are administered over a long period--often for years--it is
      important that care is taken to minimise discomfort and to reduce the incidence
      of problems at the injection site. Seepage of even small amounts of the
      medication will result in an inaccurate dose being absorbed and, owing to the
      irritant nature of many of these drugs, leakage into subcutaneous tissue and on
      to the skin surface can cause pain, irritation and lesions. This study was set up
      to compare two techniques of administering deep intramuscular injections to
      determine which best fulfilled the criteria of preventing seepage while causing
      as little discomfort as possible. The two methods used were the Z-track, which is
      standard practice in the UK, and the air bubble, which is widely taught and used
      in Canada and the USA. The study showed the air-bubble method to be significantly
      more effective at controlling seepage than the Z-track.

PMID- 7644370
TI  - Clozapine: indications and implications for treatment.
AB  - The history, pharmacological properties, interactions and clinical efficacy of
      clozapine are discussed, citing experimental evidence and case studies. The
      indications for using clozapine and the implications of treatment, including
      monitoring strategies, cost-effectiveness and therapeutic interventions, are
      addressed. The limitations of clozapine and scope for further research are also
      discussed.

PMID- 7644371
TI  - Named nurse. Casting fear aside.

PMID- 7644372
TI  - Same but different.

PMID- 7644373
TI  - Complementary medicine research.

PMID- 7644374
TI  - Treatment of lymphoedema.

PMID- 7644375
TI  - Assessment variations.

PMID- 7644376
TI  - Use of oxygen therapy.

PMID- 7644377
TI  - Zinc as an aid to healing.

PMID- 7644378
TI  - Cavity-wound management.

PMID- 7644379
TI  - Cleansing solution.

PMID- 7644380
TI  - Food choices of whites, blacks, and Hispanics: data from the 1987 National Health
      Interview Survey.
AB  - Dietary guidelines posit an association between diet and cancer. Different cancer
      mortality rates among whites, blacks, and Hispanics may be related to differences
      in diet. Food frequency data from the 1987 National Health Interview Survey on
      20,143 adults were used to estimate the percentage of adults, by gender and
      race/ethnicity, who consume some 59 foods six or more times per year, median
      number of servings for consumers, and frequency of consumption of skin on poultry
      and fat on red meat. On the basis of percent consumption of these foods, women
      appear to have a more diverse diet than men. Women eat more fruits and
      vegetables, less meat, and fewer high-fat foods and drink fewer alcoholic
      beverages. Whites eat a more varied diet than blacks and Hispanics; blacks eat
      more fried and high-fat food; consumption of high-fat foods is lowest among
      Hispanics. Public health messages, especially those aimed at cancer prevention,
      should be targeted at increasing the overall consumption of fruits and
      vegetables, decreasing consumption of high-fat foods, especially among white and
      black men, and increasing consumption of those healthful foods already consumed
      by particular race/ethnicity groups.

PMID- 7644381
TI  - The dietary anticancer agent ellagic acid is a potent inhibitor of DNA
      topoisomerases in vitro.
AB  - Ellagic acid and 12 related agents have been tested for their ability to inhibit
      the activities of human DNA topoisomerase (topo) I and II. Using specific in
      vitro assays, we found ellagic acid and flavellagic acid to be potent inhibitors
      of the catalytic activities of the two topoisomerases. The minimum concentration
      required to inhibit > or = 50% of catalytic activity (IC50) of ellagic acid was
      determined at 0.6 and 0.7 micrograms/ml for topo I and topo II, respectively.
      Flavellagic acid's IC50 was determined at 3.0 and 3.6 micrograms/ml for topo I
      and topo II, respectively. Unlike topoisomerase poisons, these two plant phenols
      did not trap the enzyme-DNA reaction intermediate, known as the cleavable
      complex. In contrast, ellagic acid prevented other topo I and topo II poisons
      from stabilizing the cleavable complex, suggesting that the mode of its action is
      that of an antagonist. Structure-activity studies identified the 3,3'-hydroxyl
      groups and the lactone groups as the most essential elements for the
      topoisomerase inhibitory actions of plant phenols. On the basis of these findings
      and other properties of ellagic acid, a mechanistic model for the documented
      anticarcinogenic effects of the agent is proposed.

PMID- 7644382
TI  - Proliferative response of mammary glandular tissue to formononetin.
AB  - Dietary phytoestrogens have been implicated in infertility among ruminants and
      may relate to human breast cancer risk. Formononetin is an isoflavonoid
      phytoestrogen found in animal fodder and in certain human foodstuffs. To
      investigate a possible mechanism by which phytoestrogens might influence mammary
      carcinogenesis, this study examined the capacity of formononetin to stimulate
      mammary gland proliferation. Formononetin was administered to castrated female
      BALB/c mice by daily subcutaneous injection; then mammary gland proliferation and
      estrogen receptor expression were quantified, and plasma prolactin levels were
      measured. A preliminary dose-finding study demonstrated an estrogenic effect on
      vaginal cytology when formononetin was injected at 40 mg/kg sc. Peak plasma
      concentrations of 2.5 +/- 0.8 (SD) micrograms/ml at two hours and peak mammary
      tissue concentrations of 2.0 +/- 0.2 ng/mg tissue at four hours were noted after
      a single injection at this minimally bioactive dose. Among animals treated with
      formononetin at 40 mg/kg/day for five days, mammary gland proliferation was
      enhanced 3.3-fold over saline-treated controls and was comparable to that of
      animals treated with estradiol-17 beta at 1 microgram/kg/day for five days.
      Mammary tissue estrogen receptor expression was 2-fold higher among the
      formononetin-treated animals (P < 0.01 vs. saline-treated controls), and plasma
      prolactin concentrations were increased 1.7-fold (P < 0.001 vs. saline-treated
      controls). In subsequent in vitro binding studies, formononetin competitively
      bound murine mammary estrogen receptors, but with a relative binding affinity
      15,000 times less potent than that of estradiol-17 beta. The results demonstrate
      an ability of formononetin to support mammary gland proliferation. However, the
      estrogenic potency of formononetin appears extremely weak compared with that of
      estradiol-17 beta and is roughly proportional to estrogen receptor-binding
      capacity.

PMID- 7644383
TI  - Body mass index, weight gain, and risk of endometrial cancer.
AB  - Excess weight near the time of diagnosis is a well-established risk factor for
      endometrial cancer; less is known about the influence of weight at earlier
      periods of a woman's life or weight gain in adulthood. In a case-control study in
      western New York State, interviews were conducted with 232 incident endometrial
      cancer cases, diagnosed between 1986 and 1991, and 631 community controls. Body
      mass index at 16 years of age and 20, 10, and 2 years before interview and
      changes in body mass index between these time periods were examined. While being
      relatively heavy at 16 years of age was associated with slightly increased risk
      [adjusted odds ratio (OR) = 1.28, 95% confidence interval (CI) = 0.84-1.96],
      large gains over the entire period from 16 years of age to 2 years ago (OR =
      3.45, CI = 2.13-5.57) and high body mass index close to the time of diagnosis (OR
      = 3.21, CI = 2.01-5.15) were associated with greater risk. Differences in mean
      body mass index between cases and controls increased over time.

PMID- 7644384
TI  - Influence of different diets on development of DMH-induced aberrant crypt foci
      and colon tumor incidence in Wistar rats.
AB  - The present study was undertaken to investigate certain dietary factors known to
      affect the development of colon cancer for their ability to modulate aberrant
      crypt foci (ACF). Male Wistar rats were initiated with oral doses of
      dimethylhydrazine dihydrochloride (DMH-2HCl, 20 mg/kg body wt) once a week for 10
      or 20 weeks. Throughout the study the animals were fed 1) semisynthetic casein
      based control diet, 2) control diet with 20% lard, 3) control diet with 20% lard
      and 20% dietary fiber, or 4) control diet where most of the carbohydrate pool was
      substituted with sucrose and dextrin. The composition of the different diets was
      designed to achieve equivalent intakes of essential nutrients. Animals were
      killed after 10, 20 and 31 weeks. The study showed a pronounced effect of dietary
      composition on the development of DMH-induced ACF. The diet high in sucrose and
      dextrin caused a statistically significant increase (p < or = 0.05) in the total
      number of ACF and number of small and medium ACF. Adding lard to the standard
      diet did not cause an increase in ACF, but if the dietary fiber was added to the
      high-fat diet, a statistically significant reduction (p < or = 0.05) in the total
      number of ACF and number of small and medium ACF was observed. The values of
      large and extra-large foci reflected the same effect of diets on ACF. The results
      indicate that tumors in the group fed the diet high in refined carbohydrates were
      more prominent and occurred with a higher incidence. However, the difference is
      based on few tumors and is not statistically significant.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7644386
TI  - Effect of carotenoids on in vitro immunoglobulin production by human peripheral
      blood mononuclear cells: astaxanthin, a carotenoid without vitamin A activity,
      enhances in vitro immunoglobulin production in response to a T-dependent
      stimulant and antigen.
AB  - The effect of carotenoids on in vitro immunoglobulin (Ig) production by
      peripheral blood mononuclear cells (PBMNC) was examined by employing blood
      samples from adult volunteers and full-term newborn babies (umbilical cord
      blood). Under carotenoid-supplemented culture conditions, cells were stimulated
      by polyclonal stimulants, neoantigens, and a recall antigen (Ag), and IgM, IgA,
      and IgG levels in the culture supernatant were measured. Beta-carotene and
      astaxanthin were used as representatives of carotenoids with and without vitamin
      A activity, respectively. Astaxanthin enhanced IgM production in response to T
      dependent Ag (TD-Ag) and a T-dependent polyclonal stimulant. Astaxanthin also
      augmented IgG production in response to a recall Ag. IgA production without
      supplemental carotenoids was negligible for all stimuli. However, in carotenoid
      supplemented cultures, IgA production was significantly higher in response to a T
      dependent polyclonal stimulant than in unsupplemented cultures. IgM and IgA
      production was augmented at 10(-8) mol/l astaxanthin, whereas astaxanthin
      enhanced IgG production in response to a recall Ag at 10(-10)-10(-9) mol/l.
      Similar enhancing actions of astaxanthin on IgM production were observed in cord
      blood mononuclear cells (CBMNC), although CBMNC produced less IgM than adult
      PBMNC. Beta-carotene did not have a significant effect on human Ig production.
      The carotenoid actions were not demonstrated under serum-free culture conditions;
      serum is essential for solubilization of carotenoids. In summary, this study has
      shown for the first time that astaxanthin, a carotenoid without vitamin A
      activity, enhances human Ig production in response to T-dependent stimuli.

PMID- 7644385
TI  - Dietary correlates of fat intake.
AB  - Dietary fat intake has been associated with the development of chronic diseases,
      including heart disease and cancer, in human populations; however, associations
      demonstrated between disease and fat intake may be confounded by related dietary
      factors. Therefore, description of the correlates of fat intake in free-living
      adults may help identify important confounders independent of disease status. In
      a population of 863 women and 538 men between the ages of 50 and 85 randomly
      selected from two counties in western New York, we found that most nutrients were
      correlated with grams of total fat intake including protein, carbohydrates,
      cholesterol, dietary fiber, retinol, iron, and calcium. Carbohydrates and dietary
      fiber were not related to the concentration of fat in the diet (% of energy from
      fat). Alcohol intake was negatively associated with fat concentration for men but
      not for women. Particularly important for the study of cancers, the antioxidants
      carotene and ascorbic acid were negatively associated with fat concentration in
      the diet.

PMID- 7644387
TI  - Effect of enteral formulas on methotrexate toxicity.
AB  - Type of diet influences toxic effects of the chemotherapeutic drug methotrexate
      (MTX) on the gastrointestinal tract (GI) tract. In this study, commercial enteral
      products containing various protein types were tested to determine whether they
      exacerbated or alleviated MTX-induced GI toxicity in a non-tumor-bearing animal
      model receiving a single injection of MTX (20 mg/kg). Five enteral products
      containing casein or soy isolate in various forms as the primary source of
      protein were used. One casein-based product also contained soy fiber. These diets
      were compared with a soy concentrate-based diet and a casein-based diet prepared
      by the authors. Each diet was fed to 10 rats for seven days before injection and
      seven days after injection. In animals fed soy isolate or hydrolyzed or intact
      casein without added soy fiber, food intake was < 30% of pre-MTX injection levels
      on Days 3 and 4 after injection. These animals also lost weight and had diarrhea.
      Rats consuming the casein-based diet with fiber experienced some protection
      against MTX toxicity. Food intake only dropped to 63% of preinjection levels,
      weight was maintained, and no diarrhea occurred. Rats fed soy concentrate
      maintained food intake above 90% of preinjection levels, which was greater than
      all other groups at Day 3 and those receiving hydrolyzed or intact casein without
      fiber on Day 4 (p < 0.05). Weight gain in the soy concentrate group was also
      different from that in groups fed hydrolyzed or intact casein without fiber (p <
      0.05). Rats consuming soy concentrate had no diarrhea. A second experiment was
      conducted to evaluate histological damage to the intestine when these diets were
      fed to animals injected with MTX. This experiment was conducted in the same
      manner as the first experiment, except animals were sacrificed on Day 3 after
      injection and samples were obtained from the jejunum. Crypt necrosis occurred in
      all groups except those consuming the soy concentrate diet or the enteral product
      containing soy fiber. Results indicate that soy concentrate is superior in
      alleviating MTX toxicity compared with commercial enteral products.

PMID- 7644388
TI  - Effect of diets on 5-fluorouracil and cyclophosphamide toxicity.
AB  - Feeding rats a semipurified diet containing casein as a protein source results in
      severe gastrointestinal (GI) toxicity when the chemotherapeutic drug methotrexate
      (MTX) is given. However, when soy concentrate protein is used in place of casein,
      rats are completely protected from toxicity. The purpose of this study was to
      determine whether soy protein was also protective against two other
      chemotherapeutic agents, 5-fluorouracil (5-FU) and cyclophosphamide (CY), which
      are routinely used in a multidrug regimen with MTX in a clinical setting. Three
      diets were tested; they consisted of a control complex diet (rat chow) and two
      semipurified diets containing casein or soy concentrate as the protein fraction
      given to non-tumor-bearing rats receiving a single injection of 5-FU or CY at
      three different levels (Experiment I: 5-FU: 100, 260, and 420 mg/kg; Experiment
      II: CY: 120, 180, and 240 mg/kg). Each diet was fed to seven rats for seven days
      before injection and seven days after injection. Food intake decreased at Day 3
      in all groups receiving 5-FU (35-90% reduction from preinjection level), with the
      greatest decrease associated with the group receiving the highest drug level.
      Animals fed the control diet ate consistently less than animals fed the other two
      diets regardless of the drug level. Intake was not significantly different
      between the casein and soy concentrate groups at any drug level. Animals gained
      weight on the low-dose treatment regardless of diets. At 260 and 420 mg/kg 5-FU,
      all diet groups lost weight, but the difference was significant only between the
      control and the two other diets (p < 0.05). Diarrhea was absent in the casein
      diet groups, regardless of drug dose, and present in the other diet groups. Food
      intake decreased on Day 1 for all groups receiving CY. At any dose, the control
      diet group maintained a greater intake on Day 1 than the other two diet groups.
      The difference in intake was significant between the control and the two other
      diet groups at low dose, between the control and the casein diet groups at 180
      mg/kg, and between the control and the soy concentrate diet groups at high dose
      (p < 0.05). All animals lost weight regardless of diet and drug dose. A third
      experiment was conducted to evaluate histological damage to the intestine when
      these three diets were fed to animals injected with 420 mg/kg 5-FU.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7644389
TI  - Calcium phosphate supplementation results in lower rat fecal bile acid
      concentrations and a more quiescent colonic cell proliferation pattern than does
      calcium lactate.
AB  - Although there is general agreement that dietary calcium is protective against
      colon carcinogenesis, considerable controversy exists on the relative efficacy of
      the counterion in calcium supplements. We therefore conducted a comparative study
      in rats of four forms of calcium supplementation (calcium phosphate, casein,
      lactate, and a 50:50 phosphate-carbonate combination). The relative effects of
      these supplements on measurements of colon physiology, in vivo pH, fecal fat,
      individual bile acids, and in vivo cell proliferation were measured in the same
      animals. In contrast to results when amounts of calcium are varied, there was no
      effect of form of supplement on total fecal output or output of fecal fat.
      Calcium phosphate resulted in the most acidified cecal contents. Calcium
      phosphate and calcium casein resulted in lower fecal concentrations of
      lithocholate and lower amounts of total fecal bile acids than supplementation
      with the calcium lactate or combination diets. In addition, rats fed calcium
      phosphate had lower concentrations of fecal beta-muricholate than rats provided
      with the calcium combination supplement. In the proximal colon, calcium phosphate
      resulted in a significantly lower number of cells per crypt column and a lower
      labeling index than the calcium lactate diet. The position of the highest labeled
      cell was lower with calcium phosphate supplementation than with supplementation
      from the calcium combination or the calcium lactate diet. There was a highly
      significant correlation between the pH of cecal contents and labeling index in
      the proximal colon (r = 0.98, p = 0.003). The results suggest that calcium
      phosphate may inhibit colon tumor incidence more effectively than calcium
      lactate, because the calcium phosphate group had a lower colonic proliferative
      status than the calcium lactate group. Changes in the proliferative status of
      colonocytes are known to precede and accompany neoplasia.

PMID- 7644390
TI  - Choosing drugs for secondary prevention after myocardial infarction: a pragmatic
      approach.

PMID- 7644391
TI  - Problem-based learning in medicine: an introduction.
AB  - Problem-based learning is an innovative and challenging approach to medical
      education--innovative because it is a new way of using clinical material to help
      students learn, and challenging because it requires the medical teacher to use
      facilitating and supporting skills rather than didactic, directive ones. For the
      student, problem-based learning emphasises the application of knowledge and
      skills to the solution of problems rather than the recall of facts. It is an
      approach much favoured by curriculum planners in new and more progressive medical
      schools. This paper describes the educational basis of problem-based learning and
      gives an example of how it operates in undergraduate medical education.

PMID- 7644392
TI  - Respiratory failure in acute pancreatitis.
AB  - There are a number of important pulmonary complications of acute pancreatitis
      which make a significant contribution to the morbidity and mortality of the
      condition. The pathophysiology and management guidelines are given for each and
      approaches towards better treatment in the future are discussed.

PMID- 7644393
TI  - Is this patient fit for thoracotomy and resection of lung tissue?
AB  - Central to risk assessment for lung resection is the fact that surgery offers the
      only chance of long-term survival and cure in non-small carcinoma of the lung.
      The challenge is, therefore, to offer surgery to as many patients as possible,
      whilst avoiding the risk of death from postoperative respiratory failure. Risk
      assessment is based on careful evaluation of the patient's existing cardiac and
      respiratory disease. The use of a cardiac risk index, such as that described by
      Detsky, will ensure that cardiac risk factors are recognised and, where possible,
      ameliorated prior to surgery. Pre-existing respiratory disease may be assessed by
      arterial blood gas analysis, exercise testing, whole and regional lung function
      tests. Criteria based on these tests have been proposed to aid patient selection
      prior to lung resection. However, these criteria take no account of the
      beneficial influence on outcome of modern anaesthesia and postoperative care. The
      elimination of postoperative pain, along with techniques such as minitracheostomy
      and incentive spirometry have allowed surgery to be offered to many patients who
      would have been deemed unsuitable by standard criteria. Patients with potentially
      resectable lung cancer must never be arbitrarily excluded from surgery on the
      basis of any single criteria or test. Referral for assessment by an experienced
      team consisting of a thoracic physician, surgeon and anaesthetist will maximise
      the number of patients offered surgery for this otherwise incurable disease.

PMID- 7644394
TI  - Talking to the parents of a baby who is likely to develop permanent neurological
      impairment following a brain insult in the perinatal period.

PMID- 7644395
TI  - Syndrome X--angina and normal coronary angiography.
AB  - It is clear that angina pectoris with normal coronary arteries is a heterogeneous
      and ill-defined syndrome that encompasses different pathogenic entities.
      Differences in patient selection and in definition of 'syndrome X' has made
      comparison between different study groups rather difficult. Two decades of
      investigations have not revealed a specific cause of this syndrome. There is now
      a general belief that syndrome X probably encompasses several pathophysiological
      disease entities and the mechanisms involved in syndrome X remain to be fully
      elucidated.

PMID- 7644396
TI  - Coronary artery disease, valvular heart disease, bradycardia, and heart failure.

PMID- 7644399
TI  - Abdominal pain and acute hypotension.

PMID- 7644397
TI  - Primary duodenal carcinoma.
AB  - Eight cases of primary duodenal carcinoma in a district general hospital are
      presented. The cases highlight the advanced state of the disease at presentation,
      the difficulty in diagnosis, and its poor prognosis. Duodenal carcinoma occurs in
      both sexes worldwide with no predisposing factors in the majority of cases. There
      is an increased risk in patients with familial adenomatous polyposis and adenomas
      of the duodenum. Duodenal carcinoma occurs about 22 years from the diagnosis of
      familial adenomatous polyposis in about 2% of patients, forming over 50% of upper
      gastrointestinal cancers occurring in these patients. Carcinomatous changes occur
      in 30 to 60% of duodenal villous adenomas and much less in tubulo-villous and
      tubular adenomas. These categories of patients should be screened and adequately
      followed up. Aggressive and radical surgery, even in the presence of locally
      advanced disease and lymph node involvement, gives a better outcome. When
      curative surgery is not possible, chemotherapy must accompany palliation with or
      without radiotherapy. Pre-operative chemotherapy may facilitate a curative
      radical resection. The general five-year survival is 17-33% but some centres have
      achieved a five-year survival of 40-60% with aggressive management of these
      patients.

PMID- 7644398
TI  - Antituberculosis treatment-induced hepatotoxicity: role of predictive factors.
AB  - Antituberculosis drug-induced hepatotoxicity is quite common. However, factors
      predicting its development are still controversial. The objective of the present
      study was to evaluate the role of certain factors (age and sex of the patient,
      alcoholism, chronic liver disease, hepatitis B virus carrier status, acetylator
      status, nutritional status and antituberculosis treatment (ATT) regimen) in
      predicting the development of ATT-induced hepatitis. In a case-control study, 60
      consecutive patients with evidence of ATT-induced hepatitis were studied to
      assess the possible association of the above-mentioned factors with ATT-induced
      hepatitis. Body mass index was found to be significantly lower in ATT-induced
      hepatitis patients (17.2 +/- 2.7) than in controls (19.5 +/- 3.3) (p < 0.05).
      Pyrazinamide was used in addition to isoniazid and rifampicin in a significantly
      higher percentage of patients in the ATT-induced hepatitis group (70%) as
      compared with those in the control group (42%). No significant differences were
      observed between the two groups with regard to the rest of the parameters.

PMID- 7644400
TI  - Congestive cardiomyopathy and endobronchial granulomas as manifestations of Churg
      Strauss syndrome.
AB  - Churg-Strauss syndrome is a systemic vasculitis. Its most frequent complications
      are heart diseases and asthma. Usually, cardiological manifestations are
      pericarditis, cardiac failure and myocardial infarction. Endobronchial granulomas
      identified by bronchoscopy are unusual. We present the case of a man with
      congestive cardiomyopathy and endobronchial granulomas macroscopically visible at
      bronchoscopy. After a review of medical literature, we found one case of
      congestive cardiomyopathy and no cases of endobronchial granulomas observed by
      bronchoscopy associated with Churg-Strauss syndrome.

PMID- 7644401
TI  - Abdominal pain: do not forget Thorotrast!
AB  - The use of Thorotrast (25% thorium dioxide), a radiologic contrast agent used up
      until the mid-1950s, was associated with a wide range of malignancies, mainly of
      hepatic origin. We report a case of Thorotrast-induced hepatocarcinoma in an 82
      year-old woman.

PMID- 7644402
TI  - Covert bronchogenic cyst as a cause of life-threatening cardiopulmonary
      impairment.

PMID- 7644403
TI  - Surgical cure of hypertension in a patient with brainstem capillary
      haemangioblastoma containing neuropeptide Y.
AB  - We describe a 29-year-old woman with persistent arterial hypertension which
      resolved following complete excision of a capillary haemangioblastoma from within
      the spinal cord at the cervico-medullary junction. Immunohistochemical staining
      was positive for neuropeptide Y in capillary walls and nerves in the tumour. This
      raises the possibility of an association between neuropeptide Y and the central
      control of blood pressure in man.

PMID- 7644404
TI  - Delayed post-anoxic encephalopathy.

PMID- 7644405
TI  - Wheeze in a heart transplant patient with lymphoma.
AB  - We report a case of wheeze in a heart transplant patient who was receiving
      chemotherapy for a transplant-associated lymphoma. The patient was in severe
      respiratory distress; there were no radiological abnormalities. A diagnosis of
      invasive bronchopulmonary aspergillosis was made by bronchoscopy and
      bronchoalveolar lavage. Despite prompt antifungal therapy the patient died.
      Wheeze in a non-asthmatic immunocompromised patient, even in the absence of
      radiological abnormalities, is highly suggestive of invasive bronchopulmonary
      aspergillosis. Diagnosis is best established by bronchoscopy and examination of
      the fluid obtained by bronchoalveolar lavage; currently the response to treatment
      is often disappointing.

PMID- 7644406
TI  - Gastrointestinal haemorrhage associated with free-base (crack) cocaine.

PMID- 7644407
TI  - Spinal cord compression by spontaneous spinal subdural haematoma in polycythemia
      vera.
AB  - A woman with an eight-year history of polycythemia vera presented with numbness
      and weakness of both legs. A large spinal haematoma was revealed on magnetic
      resonance imaging which was treated clinically and which subsequently resolved.

PMID- 7644408
TI  - Gliomatosis cerebri or benign intracranial hypertension?
AB  - Benign intracranial hypertension is a condition of obscure aetiology which
      presents with episodic headaches and nausea. It is a diagnosis based on the
      exclusion of other intracranial pathology and computed tomography is usually
      normal. We present a case of gliomatosis cerebri which was initially diagnosed
      and treated as benign intracranial hypertension.

PMID- 7644409
TI  - Duodenal adenocarcinoma: uncommon cause of chronic blood loss in the elderly.

PMID- 7644410
TI  - Persistent discharging wound sinus from retained gallstone fragments following
      laparoscopic cholecystectomy.

PMID- 7644411
TI  - Stevens-Johnson syndrome following astemizole therapy.

PMID- 7644412
TI  - Sweet syndrome in chronic myeloid leukaemia.

PMID- 7644414
TI  - Fertility of male and female broiler breeders following exposure to elevated
      ambient temperatures.
AB  - Because elevated ambient temperatures decrease fertility, this study was designed
      to segregate the male and female contribution to heat stress infertility in
      broiler breeders. Eighty hens and 16 roosters at 21 wk of age were divided
      equally among two heat stress (S) and two control (C) temperature chambers. For a
      10-wk pretreatment period, all birds were maintained at an ambient temperature of
      21.1 C and 40% relative humidity. Following the pretreatment period, birds in the
      S chambers were acclimated for 1 wk at a constant temperature of 29.4 C after
      which the temperature in the S chambers was increased to 32.2 C for 8 wk. The
      temperature in the two C chambers was maintained at 21.1 C. Hens in each chamber
      were artificially inseminated on a weekly basis with 5 x 10(7) sperm per 50
      microL from either C or S males. Egg production, semen volume, spermatocrit, and
      percentage dead sperm were similar during the acclimation period, even though
      body temperature was significantly elevated in S birds (41.8 vs 41.3 C). Sperm
      penetration of the perivitelline layer overlying the germinal disc (GD) was
      decreased in eggs from hens inseminated with semen from S males compared to eggs
      from hens inseminated with semen from C males (9.5 vs 23.4 sperm per GD).
      Following the acclimation period, body temperature remained elevated in the S
      birds compared to the C birds (42.2 vs 41.3 C). Also, egg production was
      depressed in the S vs C hens (55.8 vs 82.9%). Semen volume, spermatocrit, and
      percentage dead sperm were not affected by S treatment. However, when hens were
      inseminated with semen from S males, sperm penetration of the perivitelline layer
      overlying the GD and egg fertility were decreased compared to hens inseminated
      with semen from C males (5.4 vs 14.9 sperm per GD, 45.5 vs 73.8% fertility). In
      conclusion, the male bird appears to contribute more to heat stress infertility
      than the female.

PMID- 7644413
TI  - Zinc stores in chickens delay the onset of zinc deficiency symptoms.
AB  - Three chick assays were conducted to evaluate Zn depletion rates in whole body
      and various tissues. In Assay 1, chicks fed a corn-soybean meal diet containing
      1,037 mg Zn/kg had twice as much Zn in intestine and bone and 50% more Zn in
      liver and whole body than chicks fed 37 mg Zn/kg (P < .01). In Assay 2, the
      minimum Zn requirement for growth of chicks consuming a chemically defined, amino
      acid diet was 10.6 mg Zn/kg. In Assay 3, chicks were fed the chemically defined
      diet containing either 300 or 10.6 mg Zn/kg during an 8-d pretest period, after
      which they were fed either 0 or 10.6 mg Zn/kg for 9 d. Tissue Zn concentrations
      were determined on Days 0, 1, 2, 3, 4, 5, 7, and 9 of the test period. Following
      the pretest period, Zn was higher in the liver, tibia, and small intestine, but
      not in muscle, of chicks fed 300 mg Zn/kg than of those fed 10.6 mg Zn/kg (P <
      .01). Growth of chicks switched from 10.6 to 0 mg Zn/kg was less than for chicks
      maintained on 10.6 mg Zn/kg by Day 5 (P < .05), whereas chicks switched from 300
      to 0 mg Zn/kg did not display a growth depression relative to the control until
      Day 8 (P < .05). Zinc that accumulated in the liver and small intestine of chicks
      fed the 300 to 0 Zn regimen declined until Day 3 of the test period, whereas
      tibia Zn decreased until Day 8. Chicks fed the 10.6 to 0 regimen did not display
      a substantial decrease in small intestine, liver, or tibia Zn. The data confirm
      that Zn can accumulate in bone, liver, and intestine and can subsequently be
      released for use during a period of Zn deficiency. The data also indicate that
      chicks fed a diet containing the minimum requirement of Zn cannot accumulate
      reserves of Zn that become available for use during a subsequent period of Zn
      depletion.

PMID- 7644415
TI  - Incidence of prelay squatting behavior is not related to subsequent egg laying in
      turkey breeder hens.
AB  - Sexual receptivity of turkey hens as indicated by squatting (sexual crouch) was
      evaluated in three strains of breeder hens, Nicholas (N), Hybrid (H), and British
      United (B). The incidence of squatting was compared among strains through 84 d of
      photostimulation and related to egg production characteristics. Significant
      strain, time, and strain by time interaction effects occurred for the incidence
      of squatting. In all three strains, squatting started within the 1st wk of
      photostimulation, rapidly peaked (75.0, 65.6, and 43.0% for H, B, and N hens,
      respectively) at 14 d of photostimulation, then returned to lower, basal levels
      at or before attainment of 50% hen-day egg production. Squatting incidence was
      highly variable within and between strains but was generally lower in N hens than
      H and B hens, which showed similar squatting expression. The incidence of prelay
      squatting was not correlated to onset or rate of egg production. However, there
      was a negative correlation between squatting behavior and percentage floor eggs
      in H (P = .03) hens. It was concluded that squatting incidence varies within and
      between strains of hens and is not related to subsequent egg laying performance.

PMID- 7644417
TI  - The effect of four levels of ascorbic acid and two levels of calcium on eggshell
      quality of forced-molted White Leghorn hens.
AB  - The present experiment evaluated the effect of four levels of ascorbic acid (0,
      100, 250, and 500 ppm) and two levels of calcium (3.0 and 3.5%) on the
      productivity and eggshell quality of molted Single Comb White Leghorn hens,
      housed four per 30.5 cm wide x 45.7 cm deep cage. The 4 x 2 factorial treatment
      combinations were randomly assigned to eight blocks of cages. Egg production
      increased (P < .06) an average of 5% for the levels of 250 and 500 ppm ascorbic
      acid. No differences were observed for feed consumption, egg weight, and shell
      thickness for the different levels of ascorbic acid or calcium in the diet. An
      increase (P < .01) was observed for specific gravity, as the levels of ascorbic
      acid increased. Increasing the level of calcium from 3.0 to 3.5% increased (P <
      .01) specific gravity from 1.073 to 1.075. Shell weight increased (P < .01) with
      the higher levels of ascorbic acid (250 and 500 ppm). No interactions were
      observed between the levels of ascorbic acid and calcium. Results suggest that
      supplementing ascorbic acid to molted laying hens can be beneficial to egg
      production and eggshell quality.

PMID- 7644416
TI  - The effects of extended chilling times with acetic acid on the temperature and
      microbiological quality of processed poultry carcasses.
AB  - The effects of extended chill times with and without .6% acetic acid and
      agitation on the microbiological quality of broiler carcasses were determined.
      Carcasses were chilled for either 1, 2, or 3 h using the following treatments: 1)
      paddle chiller without acid (C); 2) static ice slush with .6% acetic acid (S); 3)
      static ice slush with air agitation and .6% acetic acid (SA); and 4) a paddle
      type chiller with .6% acetic acid (P). Whole carcass rinse samples were taken at
      1, 2, and 3 h (two per time per treatment) and evaluated for total aerobes and
      Enterobacteriaceae and at 1 and 2 h for Salmonella incidence. Six replications of
      24 carcasses per replication were used for the standard microbiological
      evaluations and five runs of 24 carcasses per run were used for the determination
      of Salmonella incidence. Total aerobes were reduced (P < or = .05) by .34, .62,
      and 1.16 log10 most probable number/mL for the S, SA, and P treatments,
      respectively, when compared with the controls. Enterobacteriaceae counts were
      reduced (P < or = .05) by .50, .71, and 1.4 log10 for the S, SA, and the P
      treatments, respectively. Salmonella incidence, from inoculated carcasses, after
      1 h were 87% for the C carcasses, 80% for the S treatment, 53% for the SA
      treatment, and 6.7% for the P treatment.

PMID- 7644418
TI  - Cytogenetic study of early chicken embryos: effect of naked neck gene and high
      ambient temperature.
AB  - High ambient temperature (> 30 C) decreases fertility of breeder hens, but this
      effect has been shown to be greatly reduced in females carrying the naked neck
      gene (Na). Sixty-four females each of the three different genotypes, Na/Na
      (homozygous naked neck), Na/na+ (heterozygous), and na+/na+ (normally feathered),
      were equally distributed in two climate control rooms with individual cages, at a
      constant temperature of either 22 C or 31 C. Five hundred and seventy-six embryos
      were examined after 16 to 18 h of incubation for karyological analyses.
      Abnormalities consisted of diploid-haploid and diploid-triploid chimeras. The
      frequency of chimeric embryos was significantly affected by dam genotype. Naked
      neck females showed a much lower proportion of abnormal embryos than normally
      feathered females whatever the temperature. The highest proportion of chimeras
      was observed for the na+/na+ dams maintained at 31 C. However, the effect of
      temperature was not generally significant.

PMID- 7644419
TI  - Genetic correlations of tibial dyschondroplasia incidence with carcass traits in
      broilers.
AB  - Relationships among the incidence of tibial dyschondroplasia (TD) with 7-wk live
      BW, carcass component weights (CCW), and abdominal fat weight (AFW) were assessed
      using high and low incidence of TD lines developed by a seven-generation
      divergent selection experiment, along with a randombred control line. The
      incidence of TD exhibited negative genetic correlations with both BW (-.65 and 
      .46 estimated from sire's and dam's components of variance and covariance,
      respectively) and with CCW (< -.28). The incidence of TD and AFW was not
      correlated based on sire's components of variance and covariance. The correlation
      of TD incidence with AFW was not as high as with the other traits under
      consideration based on dam's components of variance and covariance. Correlations
      of AFW with CCW were negative based on sire's components of variance and
      covariance, but positive based on dam's components of variance and covariance.
      Heritabilities of TD, BW, AFW, and CCW estimated by sire's variance components
      were lower than those estimated by dam's variance component. Dams might have a
      greater influence on TD incidence than sires. Selection for decreasing TD
      incidence should be feasible while simultaneously increasing BW and CCW in
      broilers.

PMID- 7644420
TI  - Control of Salmonella typhimurium colonization in broiler chicks with a
      continuous-flow characterized mixed culture of cecal bacteria.
AB  - A continuous-flow culture system was used to isolate and maintain a mixed culture
      of cecal bacteria from adult broilers composed of 29 bacterial strains
      representing 10 genera. Broiler chicks were treated with the mixed culture in the
      drinking water on the day of hatch and challenged orally with 10(4) Salmonella
      typhimurium 2 d after treatment. The experiment was repeated in four separate
      trials using newly hatched chicks. The concentration of propionic acid and total
      volatile fatty acid (VFA) in the cecal contents was determined 2 d after
      treatment and at 10 d of age. Compared with controls, the number of treated
      chicks that were cecal culture-positive for Salmonella decreased (P < .01) in
      each of the trials. Additionally, the number of Salmonella in the cecal contents
      of the treated chicks at 10 d of age was decreased (P < .005) compared with
      controls in each trial. The decreased number of Salmonella in the cecal contents
      of the 10-d-old treated chicks was correlated with elevated concentrations of
      propionic acid (P < .05) and total VFA (P < .1) in the cecal contents of the
      treated chicks 2 d after treatment. The results indicated that VFA-producing
      bacteria present in the mixed culture became rapidly established in the ceca of
      the treated chicks and effectively increased resistance to S. typhimurium
      challenge.

PMID- 7644422
TI  - Campylobacter spp. in broilers on the farm and after transport.
AB  - Colonization of the ceca and contamination on carcasses of chickens by
      Campylobacter spp. was investigated. Samples were taken on the farm and after
      transport and holding. In the first set of experiments, 20 chickens, obtained
      from each of 10 broiler farms, were collected from houses containing 6- to 7-wk
      old birds. Half of the birds were slaughtered at the farm; the other half were
      transported (10 birds per chicken coop) to a holding facility and killed within
      16 to 18 h. The levels of Campylobacter spp. on the carcass and in the ceca were
      assessed. Ceca from birds in 9 of the 10 farms sampled were positive for
      Campylobacter spp. Colonization levels ranged from 10(4.11) to 10(7.28) cfu
      Campylobacter spp./g cecal matter, except on one farm, where the organism was not
      isolated. The mean count on the farm was 10(5.44) cfu Campylobacter spp./g cecal
      material, and after transport the mean was 10(6.15) cfu/g. Significant increases
      (P = .0085) in levels of Campylobacter spp. on the chicken carcasses occurred
      after transport. Levels of Campylobacter spp. enumerated from unprocessed chicken
      carcasses after transport averaged 10(7.11) per carcass, up from an average of
      10(3.66) cfu per carcass of the farm. To further verify this observation, field
      trials were conducted to assess levels on carcasses before and after commercial
      transport. Employing five farms and 200 6-wk-old chickens, the above observations
      were confirmed: prior to transport 12.1% of the chickens harbored an average of
      10(2.71) cfu per carcass, but after transport 56.0% of the chicken exteriors
      harbored an average of 10(5.15) cfu per carcass. The results of this study
      indicate that transport and holding prior to processing contributes to the
      Campylobacter spp. of > 10(4) cfu normally found on processed poultry carcasses.

PMID- 7644423
TI  - In vitro survival and multiplication of chicken myeloblasts promoted for several
      weeks by chick embryo extract.
AB  - Growth of hemopoietic cells from chick embryonic aorta, spleen, and bone marrow
      was obtained in a serum-free culture medium containing 10-d-old chick embryo
      extract. When cells were cultured in semi-solid medium (plasma clot), they
      proliferated and differentiated to generate colonies committed to the granuloid
      or erythroid lineage. Mixed colonies composed either of granulocytes and
      macrophages or granulocytes and erythroblasts were also obtained. In addition,
      two different types of colonies composed of immature cells (blast cells) could be
      distinguished by the size of the cells. These colonies were composed of larger
      cells originating from the more immature progenitors, because they developed
      after a longer incubation period. Growth of bone marrow cells up to 3 wk in
      liquid culture was also obtained in the serum-free culture supplemented with
      chick embryo extract. These cells retained a very immature phenotype and the
      ability to differentiate when reseeded in an appropriate medium. These results
      indicate for the first time that chick embryo extracts contain hematopoietic
      growth factors that are active in differentiation and proliferation of chick
      hematopoietic cells.

PMID- 7644421
TI  - Intubation of weight-selected chicks with soybean oil or residual yolk: effect on
      early growth and development.
AB  - Experiments were conducted to study the role of residual yolk on growth and
      development of chicks during the 1st wk after hatch. Surgical removal of the yolk
      sac at hatch reduced early body weight gains. Intubating chicks with a mixture of
      soybean meal and soybean oil or with residual yolk obtained from chicks at hatch
      increased body weights and enhanced development of the liver and pancreas.
      Whereas intubation with residual yolk reduced absorption of yolk sac contents,
      absorption was similar for chicks that consumed mash ad libitum or were intubated
      with the soybean meal-soybean oil diet. After cessation of yolk intubation,
      absorption of residual yolk resumed. Removal of the yolk sac decreased amylase
      and lipase activity in the pancreas. In the intestinal chyme, activity of
      amylase, trypsin, and chymotrypsin was reduced by yolk sac removal. Intubation
      with yolk increased enzyme activity (amylase excepted) in the pancreas or
      intestinal chyme only in chicks that had their yolk sacs removed. There was
      evidence that contents of the yolk sac did not enter the intestine via the yolk
      stalk, but were absorbed directly via the blood.

PMID- 7644424
TI  - Immune response to sheep red blood cells in two Smyth line populations homozygous
      for different major histocompatibility complex haplotypes.
AB  - The Smyth line (SL) chicken is characterized by a high incidence of spontaneous,
      posthatch, selective destruction of melanocytes, caused by an autoimmune
      phenomenon. It has been shown that the MHC is associated with the development and
      severity of the disease. To clarify further the role of MHC haplotypes and other
      factors leading to an autoimmune response, mean antibody titers to SRBC were
      determined for 37-wk-old females from 2 SL sublines (SL101 and SL102), each
      homozygous for a different MHC haplotype, their MHC-matched parental control
      sublines (BL101 and BL102), and a normally pigmented control, LBL. Although total
      incidence of amelanosis is approximately the same for both SL sublines,
      amelanosis occurs earlier and is more severe in SL101 birds. Within sublines,
      chickens were further classified as to the extent of the feather amelanosis.
      Neither SL MHC subline had a mean SRBC titer that differed significantly from
      unrelated LBL controls. Although the secondary response of the two sublines
      differed from each other (P < .05), neither differed from its MHC-matched
      parental control; therefore, the differences in immune response appear to be
      largely MHC-related and not closely related to melanocyte destruction. When SRBC
      titers were related to amelanotic severity, no differences were found within the
      SL101 subline, although, SL102 birds that became amelanotic at a later age had a
      lower primary response to SRBC (P < .05) than the more severely affected group.
      Birds simultaneously producing both pigmented and amelanotic feather tissue had
      higher (P < .05) primary and secondary anti-SRBC titers than did the complete
      amelanotics.

PMID- 7644425
TI  - Utilization of hydrolyzed sucrose polyester (olestra) in broiler diets.
AB  - Three experiments were conducted in which hydrolyzed olestra (HO) and hydrolyzed
      olestra manufacturing by-product (HBP) were compared with corn oil (CO) and a
      feed-grade hydrolyzed animal-vegetable fat blend (AVF) as fat supplements in
      diets for broilers. Various blends of HO and HBP with AVF and other fat sources
      were also evaluated. Results of these experiments indicate that HO or HBP may be
      used as energy sources in broiler diets. Use of these materials as the sole
      source of supplemental fat often reduced body weight gain and impaired feed
      utilization as compared with CO or AVF; however, when used as a component of a
      blended fat product typical of industry supplements, there was little if any
      adverse effect on live performance. Carcass fatty acid content was a reflection
      of dietary fat content. If the blend of fats containing HO or HBP contains a
      suitable ratio of unsaturated and saturated fatty acids, the product should be an
      acceptable source of supplemental energy in broiler diets.

PMID- 7644426
TI  - Effects of dietary protein under high ambient temperature on body weight, breast
      meat yield, and abdominal fat deposition of broiler stocks differing in growth
      rate and fatness.
AB  - The effect of dietary protein on growth, feed intake and efficiency, abdominal
      fat deposition, and breast meat yield was investigated in broiler males from a
      commercial stock (WI) and from experimental stocks selected for low (LF) or high
      (HF) abdominal fat. All birds were kept at constant high ambient temperature (32
      C) and were provided with low- (LP) or high-protein (HP) diets from hatch until 8
      wk of age (Experiment 1) or from 4 to 8 wk of age (Experiment 2). In both
      experiments, HP diet significantly increased 4- to 8-wk BW gain in the LF and HF
      stocks but reduced it in the WI stock as compared with the LP diet. Abdominal
      fat, as percentage of BW, was almost twofold higher in the HF birds than in the
      LF ones, with WI mean being intermediate. In contrast to the HF and WI birds, in
      which abdominal fat decreased with increased protein intake, abdominal fat was
      not affected by dietary protein in the LF stock. The HP diet substantially
      increased breast meat yield in LF birds but not in the WI birds, with HF birds
      exhibiting intermediate increase in breast meat weight. It was concluded that
      birds of varied inherent growth rate and tendencies toward protein and fat
      deposition respond differently to dietary protein level under heat stress.

PMID- 7644427
TI  - Growth performance, carcass composition, and pigmentation of broilers fed
      supplemental nickel.
AB  - Two experiments were conducted to evaluate effects of supplemental Ni on growth
      performance, carcass composition, and pigmentation of broilers. In Experiment 1,
      female broilers (n = 120) were housed in individual cages from 21 to 49 d of age
      and fed a commercial finisher diet that contained 2.4 +/- .1 ppm Ni.
      Supplementation of this diet with 6 or 12 ppm NiCl2 did not affect growth
      performance or carcass composition. In Experiment 2, female broilers (n = 60)
      housed in individual cages were fed finisher diets with 44 or 77 ppm xanthophyll
      and 0 or 12 ppm supplemental NiCl2. Growth performance from 21 to 49 d of age was
      not altered by diet. At 49 d of age, serum xanthophyll concentration as well as
      amount of lutein and total xanthophylls in skin were higher (P < or = .01) in
      broilers fed 77 ppm xanthophyll. Supplemental NiCl2 decreased (P < or = .1)
      yellow color of carcasses from broilers fed 44 ppm xanthophyll and increased
      yellow color of carcasses from broilers fed 77 ppm xanthophyll. Abdominal fat
      yields and concentration of total xanthophylls in skin followed a similar
      pattern, suggesting that supplemental NiCl2 may have indirectly influenced
      pigmentation by altering fat deposition. These data indicated that an adequate
      level of Ni was present in the basal diet to promote optimal growth performance
      and carcass quality.

PMID- 7644428
TI  - Effects of early immune stress and changes in dietary metabolizable energy on the
      development of newly hatched turkeys. 1. Growth and nutrient utilization.
AB  - Two experiments were conducted to document the effects of an early immunologic
      stress and changes in dietary ME(n) on growth and nutrient utilization of newly
      hatched turkeys. Treatments in both experiments consisted of a complete factorial
      arrangement of two types of injection and four isonitrogenous diets. Turkeys were
      injected i.p. with saline (SAL) or a solution of lipopolysaccharide (LPS) (100
      micrograms LPS/mL SAL) at 1, 3, and 5 d of age. In Experiment 1, two diets were
      formulated to contain 2,800 kcal ME(n)/kg. One was a corn-soybean meal-based diet
      (CSBM) and the other contained 8% Solkafloc (SKF). A third diet (3,100 kcal
      ME(n)/kg) was formulated by substituting 8% sucrose (SUC) for the 8% SKF. The
      fourth diet included in Experiment 1 was formulated to contain 3,700 kcal
      ME(n)/kg. The CSBM and SUC diets were also included in Experiment 2. Two
      additional diets tested in Experiment 2 were the CSBM diet containing 74.5 mg
      ibuprofen/kg (IBU) and a corn-soybean meal-based diet with a ME(n) value of 3,100
      kcal/kg (CS31). Injection with LPS reduced (P < .05) BW of turkeys throughout
      Experiment 1 and until 9 d of age in Experiment 2, as compared with injection
      with SAL, irrespective of dietary treatment. The reduction in BW was mainly due
      to a decrease in feed intake (FI) (P < .05). Turkeys fed diets with 3,100 kcal
      ME(n)/kg were heavier (P < .05) than those fed diets with 2,800 kcal ME(n)/kg,
      irrespective of injection. Inclusion of ibuprofen to the CSBM diet from 1 to 14 d
      improved (P < .05) BW and feed efficiency (P < .01) of turkeys at 14 d of age,
      compared with turkeys fed the CSBM diet. Determined ME(n) was not affected by LPS
      injection. Adverse effects of LPS injection on growth of turkey poults were
      mainly the consequence of a reduced FI and not of altered nutrient utilization.
      These effects were not fully alleviated by feeding a diet with 3,100 kcal
      ME(n)/kg.

PMID- 7644430
TI  - The 7th International Conference on Early Prenatal Diagnosis: some personal
      impressions.

PMID- 7644429
TI  - Effects of early immune stress and changes in dietary metabolizable energy on the
      development of newly hatched turkeys. 2. Selected characteristics of immune
      function.
AB  - Two 21-d experiments were conducted to document the effects of an early
      immunologic stress and changes in dietary ME(n) on selected characteristics of
      immune function of newly hatched turkeys. Eight treatments were included in each
      experiment. Treatments were the result of complete factorial arrangements of two
      types of injection and four isonitrogenous diets. Turkeys in both experiments
      were injected i.p. with .5, .5, and .2 mL of saline (SAL) or .5, .5, and .2 mL of
      a solution of Escherichia coli lipopolysaccharide (LPS) (100 micrograms LPS/mL
      SAL) at 1, 3, and 5 d of age, respectively. In Experiment 1, two diets were
      formulated to contain 2,800 kcal ME(n)/kg. One was a corn-soybean meal based diet
      (CSBM) and the other contained 8% Solkafloc (SKF). A third diet (3,100 kcal
      ME(n)/kg) was formulated by substituting 8% sucrose (SUC) for the 8% SKF. The
      fourth diet (HE) included in Experiment 1 was formulated to contain 3,700 kcal
      ME(n)/kg. The CSBM and SUC diets and two additional diets were tested in
      Experiment 2. The latter were the CSBM diet containing 74.5 mg ibuprofen/kg (IBU)
      and a corn-soybean meal diet formulated to contain 3,100 kcal ME(n)/kg (CS31).
      Concentrations of plasma IgG and jejunal IgG and IgA were not affected by
      injection or diet. Age-related changes in Ig concentrations were consistently
      observed in Experiments 1 and 2. Injection with LPS reduced the number or
      responses of blood leukocytes to mitogens at 8 d of age (P < .01), as compared
      with samples from turkeys injected with SAL. Leukocytes in whole blood samples
      from turkeys fed the HE diet responded less to LPS stimulation than those fed the
      SUC diet (P < .01). Injection with LPS did not markedly affect the
      characteristics of immune function studied, and feeding a diet with 3,100 kcal
      ME(n)/kg and 28.5% crude protein did not measurably affect the characteristics of
      immune function of young turkeys.

PMID- 7644431
TI  - Prenatal prediction in families with autosomal recessive proximal spinal muscular
      atrophy (5q11.2-q13.3): molecular genetics and clinical experience in 109 cases.
AB  - Prenatal prediction in families at risk for autosomal recessive proximal spinal
      muscular atrophy (SMA) mainly of type I is often requested due to the high
      incidence and the fetal outcome of the disease. So far, only indirect genotype
      analysis can be performed in SMA families, since the gene has not yet been
      identified. We present our experience of 109 prenatal diagnoses obtained in 91
      families by use of single- and multi-locus polymorphic microsatellites of the
      region 5q11.2-q13.3. The marker combinations and specific features of the closest
      microsatellites are described in detail. From 137 requests for prenatal
      prediction of SMA between October 1991 and August 1994, 28 families were
      excluded, mostly because the clinical diagnosis was uncertain or doubtful. Others
      had to be classified as 'SMA-variants' or showed autosomal dominant transmission
      of SMA. Of the 109 prenatal diagnoses performed, 29 fetuses were diagnosed to be
      at high risk (> 99 per cent) of developing the disease, while in seven additional
      pregnancies no exact prediction could be made due to a recombination event in one
      parental haplotype. Altogether, recombinations between closely flanking markers
      were observed in 14 cases. In 35 cases, the parents decided to terminate the
      pregnancy. Of the remaining pregnancies, 32 could be followed beyond term. All
      infants were reported to develop normally without signs of SMA. Two children were
      born with transverse reduction defects of one hand, which was most likely related
      to early chorionic villus sampling at 9 and 10 weeks' gestation. No further
      abnormalities could be detected. The limits of indirect genotype analysis and the
      problems of diagnostic accuracy and heterogeneity of proximal SMA are discussed.

PMID- 7644432
TI  - Sonographically determined anomalies and outcome in 170 chromosomally abnormal
      fetuses.
AB  - Structural pathology and outcome were studied in 170 chromosomally abnormal
      fetuses. Numerical chromosomal abnormalities were established in 158 (93 per
      cent) cases, of which 110 (71 per cent) represented trisomies, 30 (18 per cent)
      Turner syndrome, and 18 (11 per cent) triploidy. Structural chromosomal
      abnormalities were diagnosed in 12 (7 per cent) cases. Gestational age at
      referral was significantly shorter for pregnancies with Turner syndrome than for
      the other chromosomal abnormalities. Referral before 20 weeks of gestation was
      mainly based on fetal structural pathology alone (92 per cent); after 20 weeks,
      patients were referred because of structural pathology combined with small for
      gestational age, oligohydramnios, or polyhydramnios. Referral as a result of
      suspected multiple organ pathology occurred in 73.5 per cent of pregnancies. An
      abnormal amniotic fluid volume was present in 59/170 (34.5 per cent)
      chromosomally affected pregnancies, i.e., oligohydramnios in 31 and
      polyhydramnios in 28 cases. Birth weight was below the tenth percentile in over
      half of the chromosomally abnormal fetuses, except for Turner syndrome. Fetal
      outcome was poor, with a survival rate at 1 month of 30 per cent for trisomies
      which was mainly determined by trisomy 21 (14/18 = 77.5 per cent).

PMID- 7644433
TI  - The role of percutaneous umbilical blood sampling in the management of immune
      thrombocytopenic purpura.
AB  - On consultation, percutaneous umbilical blood sampling (PUBS) was offered to
      women with immune thrombocytopenic purpura (ITP) to determine the mode and site
      of delivery prior to labour. Between January 1989 and December 1993, 41 pregnant
      women underwent PUBS. All women had a history of ITP, a platelet count less than
      90 K, (+) antiplatelet antibody, and/or thrombocytopenia diagnosed early in
      pregnancy. PUBS was performed at term except in one patient with preterm labour,
      who underwent PUBS at 31 weeks' gestation. Patients with fetal platelet counts
      greater than 50 K returned to their referring physician for delivery. Records
      were complete in 39 pregnancies. Fetal blood was successfully obtained in 37 of
      39 cases (95 per cent). Fetal platelet counts correlated with neonatal platelet
      counts in 36 of 37 cases (97 per cent). The interval between PUBS and delivery
      ranged from 0 to 31 days. Six of 37 fetuses (16 per cent) had significant fetal
      thrombocytopenia (< 50 K). These six patients underwent Caesarean section.
      Vaginal delivery was recommended in all others. There were two procedure-related
      complications. There were no cases of intraventricular haemorrhage in any of the
      neonates. In conclusion, there is a high incidence of fetal thrombocytopenia in
      women with ITP. PUBS reliably detects fetal thrombocytopenia and is therefore
      useful in the perinatal planning of the mode and site of delivery.

PMID- 7644434
TI  - Ultrasound observation of amnion dysmorphism at 14.5-16 weeks.
AB  - The presence of chorio-amniotic separation and amnion anomalies was recorded in
      9500 patients referred for vaginal ultrasound examination at 14.5-16 weeks'
      gestation. In all patients with a change in the amnion, a search for fetal
      anomalies was performed and pregnancy outcome was checked. Amnion dysmorphism was
      observed in 30 cases. The main findings were a floating membrane which changed
      its configuration when the uterus was tilted and multiple intrauterine amniotic
      sheets. In no case was attachment of the fetus to the membranes noted. There was
      no fetal abnormality and pregnancy outcome was favourable in all patients. In
      conclusion, ultrasound visualization of amnion dysmorphism in early pregnancy is
      not associated with an adverse pregnancy outcome.

PMID- 7644435
TI  - Thyroid antibodies are not a risk factor for pregnancies with Down syndrome.
AB  - The observation that thyroid disease is frequent in mothers of children with Down
      syndrome (DS) has suggested that maternal thyroid antibodies could be a factor
      predisposing to trisomy 21 in their offspring. In this study, the incidences of
      thyroglobulin (Tg) and thyroid peroxidase (TPO) antibodies were analysed with a
      sensitive solid-phase immunosorbent radioassay in sera from 29 mothers giving
      birth to children with trisomy 21 and 87 control mothers. The serum samples were
      collected at delivery. There was no statistical difference regarding the
      proportion of thyroid antibodies (against Tg and/or TPO) in the two groups.
      Thyroid antibodies were detected in 6/29 (20.7 per cent) of the DS mothers and in
      23/87 (26.4 per cent) of the control mothers. Among the women with thyroid
      antibodies, 4/6 (66.7 per cent) of the DS mothers and 12/23 (52 per cent) of the
      control mothers had antibodies against both Tg and TPO. There was no increase in
      the relative risk of having a child with DS if the titre of either Tg or TPO
      antibodies or both were positive, i.e. > or = 1/5. The results indicate that the
      presence of thyroid antibodies in the serum of a pregnant women has no prognostic
      value for the birth of an infant with DS.

PMID- 7644436
TI  - New estimates of Down syndrome risks at chorionic villus sampling, amniocentesis,
      and livebirth in women of advanced maternal age from a uniquely defined
      population.
AB  - Current measures of livebirth prevalence of Down syndrome are derived from data
      obtained up to 20 years ago, before the introduction of the prenatal diagnostic
      tests amniocentesis and chorionic villus sampling (CVS). For women aged 36-52
      years, but who were not tested prenatally, we proposed to make a direct estimate
      of current livebirth prevalence of Down syndrome. We could also determine
      prevalence at the time of CVS and amniocentesis in women of the same age
      undergoing prenatal testing. Differences in these prevalences allow an estimation
      of the relative loss of Down syndrome during pregnancy. In Victoria, Australia,
      we identified 3041 women having CVS, 7504 having amniocentesis, and 13,139 having
      no test. Smoothed regression estimates of age-specific livebirth prevalence were
      found to be higher than in the early studies. The estimate of spontaneous loss
      was 17 per cent between the time of CVS and amniocentesis, and 18 per cent after
      the time of amniocentesis. The latter figure is lower than previous estimates and
      may be explained by a greater likelihood of a Down syndrome fetus surviving to be
      liveborn, given the modern approach to early obstetric intervention. These
      current risk estimates of livebirth may be useful updates for genetic
      counselling, but perhaps more importantly, may be used as precise maternal age
      related risk figures, necessary in the design and implementation of prenatal
      screening programmes for Down syndrome.

PMID- 7644437
TI  - Prenatal diagnosis in two cases of de novo complex balanced chromosomal
      rearrangements. Three-year follow-up in one case.
AB  - We report two cases of apparently balanced complex de novo chromosomal
      rearrangements (BCCR) detected prenatally at 17 weeks and 10 weeks of gestation,
      respectively. Chromosomes were studied using GTG-banding and fluorescent in situ
      hybridization (FISH). In one case four chromosomes and in the other case three
      chromosomes were involved in the rearrangements. One of the pregnancies was
      terminated and no external or internal showed no abnormalities. The child is now
      3 years old and has neither congenital anomalies nor evidence of delayed
      psychomotor development.

PMID- 7644439
TI  - Prenatal diagnosis of autosomal recessive osteopetrosis, infantile type, by X-ray
      evaluation.
AB  - Prenatal diagnosis for infantile osteopetrosis was attempted during the third
      pregnancy of a first-cousin marriage whose family history revealed an affected
      previous child. At the 25th week of pregnancy, fetal X-ray evaluation revealed
      marked sclerosis of osteopetrotic bone and metaphyseal splaying and clubbing of
      both femurs. The pregnancy was terminated and repeated X-rays and
      histopathological examination of fetal bone (femur) confirmed the diagnosis.

PMID- 7644438
TI  - Prenatal exclusion of the HHH syndrome.
AB  - Prenatal diagnosis of the hyperornithinaemia, hyperammonaemia, and
      homocitrullinuria syndrome is described by the analysis of ornithine
      incorporation in second-trimester cultured amniotic fluid cells. An unaffected
      fetus was predicted and confirmed in the newborn child. This is the third
      reported prenatal diagnosis for this disorder and the second predicting an
      unaffected fetus.

PMID- 7644440
TI  - A misdiagnosis of X-linked adrenoleukodystrophy in cultured chorionic villus
      cells by the measurement of very long chain fatty acids.
AB  - A case is reported of a male fetus at risk of X-linked adrenoleucodystrophy who
      showed a normal cultured chorionic villus cell very long chain fatty acid (VLCFA)
      profile but at birth exhibited grossly abnormal plasma and cultured fibroblast
      VLCFAs. Maternal contamination or a sample mix-up was excluded by chromosome
      analysis and analysis of polymorphic markers. This is the second report of a
      fetus affected with this disorder who showed normal cultured chorionic villus
      cell VLCFAs. It highlights the importance of a proper audit of all prenatal
      diagnoses to evaluate method reliability.

PMID- 7644441
TI  - Current awareness in prenatal diagnosis.

PMID- 7644442
TI  - American Health Foundation Child Health Risk Reduction Workshop: Recommendations.
      Improving child health and child health behavior: an agenda for action.

PMID- 7644443
TI  - Psychosocial correlates of healthful diets: baseline results from the Working
      Well Study.
AB  - BACKGROUND: This report examines psychosocial factors related to selection of
      healthful diets. Understanding why people select healthful diets can lead to
      rational design and evaluation of nutrition intervention programs. METHODS: Data
      are from 16,287 respondents to the baseline survey for the Working Well Trial, a
      randomized, controlled trial of worksite-based health promotion. The psychosocial
      constructs we measured were predisposing factors (beliefs, perceived benefits,
      and motivation; 5 items, Cronbach's alpha = 0.65) and enabling factors (barriers,
      norms, and social support; 6 items, Cronbach's alpha = 0.57). The healthful diet
      outcomes were intakes of fat, fiber, and servings of fruits and vegetables (from
      a food frequency questionnaire) and intention and self-efficacy to decrease fat
      and increase fruits and vegetables. RESULTS: Based on a 5-point scale (1 = low to
      5 = high), the mean predisposing factor scale score was much higher than the
      enabling factor scale score (3.77 vs 2.50, P < 0.001). Comparing respondents in
      the highest category of the predisposing scale to those in the lowest, mean
      percentage of energy from fat was 22.4% lower (-9 percentage points), fiber was
      85.2% higher (+4.6 g/1,000 kcal), and fruits and vegetables were 100% higher
      (+1.6 servings/day) (all trends, P < 0.001). Associations were similar, but much
      weaker, for the enabling scale. Multiple regression models, which included
      covariates related to diet and the predisposing and enabling scales, explained a
      total of between 13 and 26% of the variance in diet and intention to change diet.
      After control for covariates, the predisposing scale remained a significant and
      strong predictor of diet and intention to change diet but the enabling scale
      explained small and nonsignificant amounts of variance. CONCLUSIONS: Predisposing
      factors are strong predictors of current diet and intention to change diet. Final
      results from the Working Well Trial will provide more information on whether
      enabling factors can be enhanced by intervention and whether these changes result
      in healthier eating patterns.

PMID- 7644444
TI  - Alcohol use and reported physician visits in older adults.
AB  - BACKGROUND: In general, older adults use a greater proportion of health care
      services than other age segments of the population. Alcohol abusers also use a
      greater proportion of health care services than alcohol nonabusers. Therefore we
      expected that among older adults, alcohol consumption would be positively related
      to health service use. In a sample of older adults, this study examined the
      relationship between alcohol consumption and an indicator of health service use-
      the self-reported number of physician visits. METHODS: Data obtained on adult
      participants in the 1990 National Health Interview Survey, age 60 and older (n =
      10,522), were examined. The number of physician visits was regressed on health
      status and alcohol consumption measures. RESULTS: Counter to a priori
      expectations, alcohol consumption was negatively associated with physician
      visits. This finding was obtained after adjusting for respondent sex and health
      status measures. CONCLUSIONS: Other research suggests that the rates of alcohol
      related hospital admissions among older adults are on par with those of
      myocardial infarctions--an indication that harmful use of alcohol in older adults
      is going undetected. We found heavier alcohol consumption associated with fewer
      physician visits. This underscores the need for a better understanding of the
      role alcohol serves in the health perceptions of older adults. Broadening our
      knowledge in this area would be of benefit not only to the well-being of
      individuals also for health services policy considerations.

PMID- 7644445
TI  - The smoking cessation process: longitudinal observations in a working population.
AB  - BACKGROUND: Few prospective studies have investigated variables related to the
      smoking cessation process in nonvolunteer samples. METHODS: Smoking history,
      behavioral intentions, degree of addiction, and demographic characteristics were
      examined over a 2-year period as predictors of four behavioral outcomes related
      to smoking cessation--participation in a smoking cessation program, attempting to
      quit, relapse, and success in quitting--in 802 working adults who were daily
      smokers at baseline. Change in behavioral intentions over the 2-year period was
      also examined. RESULTS: Sixty-four percent of smokers made a serious quit attempt
      in the 2-year study period, 16% succeeded in quitting, and an additional 9%
      shifted from daily to occasional smoking. Stated intention to quit at baseline
      was a powerful and consistent predictor of three of the behavioral outcomes, but
      several demographic and smoking-related variables were differentially associated
      with these three outcomes. CONCLUSIONS: Study findings indicate that smoking
      cessation is a dynamic process in which a majority of smokers are actively
      engaged. Smoking pattern and sociodemographic characteristics are predictors of
      whether smokers will participate in programs, make quit attempts, and succeed in
      quitting. Intention to quit is related to smoking outcomes in a manner that would
      be predicted by the Transtheoretical Model of Behavior Change.

PMID- 7644447
TI  - Sigmoidoscopy use among primary care physicians.
AB  - BACKGROUND: Despite endorsement by a variety of professional societies, screening
      sigmoidoscopy is performed on a small minority of patients. We performed a survey
      of primary care physicians in Allegheny County to examine in detail their current
      practice and attitude toward screening sigmoidoscopy. METHODS: Physicians were
      surveyed by mail or telephone. Eligible respondents were required to practice in
      the county and perform direct patients care. RESULTS: Of 732 adult primary care
      physicians in Allegheny County, 400 were randomly selected for sampling and 279,
      or 70%, responded. Over 88% of physicians agreed completely or partly with
      current American Cancer Society recommendations for screening sigmoidoscopy, but
      only 34% (95% CI 29-39%) reported they regularly refer or schedule patients for
      screening. Physicians who screen were more likely to be from internal medicine or
      family practice (P < 0.001) and to be trained in (P < 0.001) or to personally
      perform (P < 0.001) sigmoidoscopy. The greater the number of barriers to
      screening cited by physicians, including cost, patient discomfort, equipment
      availability, low probability of finding a lesion, time it takes to do
      sigmoidoscopy, and the risk of the procedure, the lower the screening rate (P =
      0.002). CONCLUSION: (a) Although primary care physicians in Allegheny County
      report that they support screening sigmoidoscopy, only one-third regularly refer
      or schedule patients, (b) physicians who are trained in or who perform
      sigmoidoscopy are more likely to screen patients, and (c) further education and
      training of primary care physicians in sigmoidoscopy will be required to increase
      screening rates.

PMID- 7644446
TI  - The perception of the menopause and the climacteric among women in Hong Kong and
      southern China.
AB  - BACKGROUND: A lack of awareness of the long-term consequences of the menopause
      may be a major contributing factor to the low demand for hormone replacement
      therapy in Hong Kong and China. Most Chinese women suffer few acute menopausal
      symptoms, and it was our hypothesis that they had little knowledge of the risks
      of developing either osteoporosis or cardiovascular disease as a result of
      estrogen deficiency. METHODS: A prospective study was conducted among 200 Chinese
      women of all ages living in Hong Kong or southern China. A structured
      questionnaire was used to examine their perception of the menopause and the
      climacteric. RESULTS: While 96% of women from Hong Kong and 73% from southern
      China could define the menopause, none in either group were aware of the problems
      of either osteoporosis or cardiovascular disease in post-menopausal women. Only
      8% of women from Hong Kong and 4% from southern China knew that hormone
      replacement therapy could be used to treat postmenopausal women. CONCLUSIONS: The
      results of this study confirm a relative lack of understanding of the climacteric
      in both groups of Chinese women. As menopausal symptoms are also infrequent in
      this population, most women will not have the need to consult a physician and
      will therefore not have the option of taking hormone replacement therapy to
      prevent the long-term effects of estrogen deficiency. Considering the sizes of
      the populations involved, the potential for reducing morbidity and mortality
      through improved education about the menopause is considerable.

PMID- 7644448
TI  - Assessing breast self-examination.
AB  - BACKGROUND: Women practice breast self-examination (BSE) according to their own
      schedule and skill. This variation in how BSE is performed has complicated the
      interpretation of studies of BSE efficacy and utilization. METHODS: We compared
      two methods commonly used to assess BSE competency, self-report of practice and
      ability to detect lumps in a model, among 81 women participating in a controlled
      toxicity trial of tamoxifen. Subjects were postmenopausal, were under 65 years of
      age, and had a history of breast cancer within the past 10 years but were
      currently free of disease. Women were asked to describe their usual BSE practice
      and were assigned a score (0-10) based on the number of recommended techniques
      and positions mentioned. Subjects were then instructed to examine a silicone
      breast model embedded with lumps (HealthEdCo) and to report any abnormalities.
      RESULTS: Overall proficiency was low by both measures. No significant correlation
      (r = 0.16, P = 0.15) was found between the two measures of proficiency. Higher
      correlations were observed among older women and among those practicing BSE
      monthly. CONCLUSIONS: This study suggests that the two techniques are not
      comparably evaluating BSE proficiency. Further, both of these methods are likely
      to be poor measures of true BSE practice.

PMID- 7644449
TI  - Pap recency: modeling women's characteristics and their patterns of medical care
      use.
AB  - BACKGROUND: Medical care use was identified as an important predictor of Pap
      smear use in previous studies. This study scrutinized several dimensions of
      women's patterns of medical care use in relation to Pap smear use. METHODS: Cross
      sectional national household survey data were linked to the respondents' Quebec
      Medicare records for a 3-year period. Factors associated with the recency of the
      reported last Pap were analyzed in a subsample of women ages 18-35 years (n =
      1,799) by logistic ordinal regression. The resulting models were tested in a
      confirmatory sample (n = 1,799). RESULTS: Three dimensions of medical care use
      were examined while adjusting for women's characteristics. Recency of testing was
      associated with the volume of ambulatory visits to general  practitioners and to
      obstetrician-gynecologists, with the regularity of care, and with the number of
      different physicians visited. CONCLUSIONS: Women's pattern of medical care use,
      especially the regularity of care, was an important predictor of Pap recency.
      Results suggest targets for improvement of screening coverage and highlight the
      critical role of general practitioners.

PMID- 7644450
TI  - The seven health practices, well-being, and performance at work: evidence for the
      value of reaching small and underserved worksites.
AB  - BACKGROUND: Research conducted over several decades demonstrates rather
      convincingly that seven health practices predict future mortality rates,
      morbidity, and disability. The current study was designed to determine the extent
      to which these health practices predict more proximal wellness and illness
      factors. METHOD: Data were collected from 345 employees working in a variety of
      organizations in southern California. In addition, supervisors evaluated the
      attendance record and job performance of the participating employees whom they
      directly supervised. RESULTS: Analyses revealed that, after adjusting for age,
      gender, ethnicity, occupational status, and employee social relations, the seven
      health practices significantly predicted several employee wellness factors (i.e.,
      vitality, positive well-being, and supervisory ratings of attendance) and illness
      factors (i.e., anxiety, depression, lack of self-control, and physical illness
      behavior). Employee social relations also predicted unique variance in most of
      the wellness and illness factors. However, neither employee health practices nor
      social relations predicted supervisory ratings of job performance. CONCLUSION:
      The pattern of findings was remarkably similar to previous work demonstrating the
      more distal impact of the seven health practices and suggests the value of
      encouraging good employee health practices at small and underserved worksites.

PMID- 7644451
TI  - Agreement between self-reported early cancer detection practices and medical
      audits among Hispanic and non-Hispanic white health plan members in northern
      California.
AB  - BACKGROUND: Using the medical records of a large, prepaid health plan, our
      purpose was to assess the accuracy of self-reported data on cancer detection
      practices and to evaluate any differences in accuracy between Hispanics and non
      Hispanic whites. METHODS: Data were collected on six procedures: mammography,
      clinical breast examination, Pap smear, sigmoidoscopy, fecal occult blood tests,
      and digital rectal examination. We audited the medical records of 815 randomly
      selected Hispanic and 483 non-Hispanic white members of the Kaiser Permanente
      Medical Care Program in Northern California. All responded to a telephone survey.
      Using a standardized form, we recorded any of the six target examinations that
      had been performed within 5 years of the telephone interview. We then compared
      the times of the most recent screening tests as reported in the telephone survey
      with those in the medical record. RESULTS: For the 2 years before the telephone
      interview, self-reports for screening tests overestimated the actual rates at
      which these tests were performed as documented in the medical records. Lack of
      agreement between self-report and medical record audits was substantial for all
      screening procedures except sigmoidoscopy. Hispanic members had fewer procedures
      done for most tests, but the differences were not statistically significant.
      Overestimates in self-reported screening rates did not differ substantially
      between Hispanics and non-Hispanic whites. CONCLUSIONS: Self-reported data on
      early cancer detection procedures can substantially overestimate their occurrence
      among both non-Hispanic white and Hispanic populations. These findings confirm
      earlier findings for Pap smear and affect decisions on cancer prevention
      procedures that rely on the accuracy of self-reported data.

PMID- 7644453
TI  - Patterns of smoking initiation in Italian males and females from 1955 to 1985.
AB  - METHODS: The changes in patterns of smoking initiation in Italian males and
      females in 1955, 1965, 1975, and 1985 were analyzed using data from the 1990-1991
      Italian National Health Survey, based on a sample of 18,483 males and 19,320
      females ages 19 to 59. The sample was randomly selected within strata of
      geographic area and size of place of residence and of household in order to be
      representative of the general Italian population. The age of each subject was
      reconstructed for each calendar year of interest (1954 to 1956, centered on 1955,
      1964 to 1966, 1974 to 1976, and 1984 to 1986). For each calendar period and year
      of age of interest (14 to 24), the numerator of the smoking initiation rate was
      the number of subjects who started smoking and the denominator was the number of
      subjects at risk, i.e., nonsmokers of the same age. The same procedure was
      repeated for three separate age groups (14 to 17, 18 to 20, and 21 to 24).
      RESULTS: Among males, there was a trend toward earlier age at start of smoking
      and higher initiation rates between 1955 and 1965, and a subsequent decline in
      initiation rate, particularly at age 18 or over and during the last calendar
      decade studied. In females, between 1955 and 1975 there was an increase of over
      fourfold in initiation rates and systematic tendencies toward earlier age at
      starting; only over the past decade have the starting rates begun to decline. The
      peak rate was reached at age 18-20 for males in 1965 (53.3%) and for females in
      1975 (23.9%). CONCLUSION: The recent declines in smoking initiation have been
      relatively limited among the younger age groups, and this reflects an earlier
      average age at smoking initiation.

PMID- 7644452
TI  - Community stop-smoking contests in the COMMIT trial: relationship of
      participation to costs. Community Intervention trials.
AB  - BACKGROUND: This study quantifies resources used to conduct 26 community-wide
      quit-smoking contests, the percentage of smokers that participated in these
      contests, and the statistical associations between resource inputs and
      participation percentages. METHODS: Data collected from the 11 COMMIT
      intervention communities (adult population range 47,490-185,913) included number
      of contest participants, contest procedures, and resource inputs. Stepwise
      regression was used to find the most meaningful association(s) of independent
      variables with contest participation percentage. RESULTS: Contest participation
      percentages ranged from 0.27 to 3.11% of smokers (mean = 1.26%). Total cost
      (COMMIT and community-contributed resources and dollar expenditures) to conduct a
      contest averaged $24,857 (range $5,751-$74,556), or $78.57 per contest
      participant. Expenditures in various specific resource categories varied greatly.
      Total expenditures per smoker in the community (excluding expenditures for
      prizes) was the independent variable most highly correlated with contest
      participation percentage, accounting for 63% of the total variability in
      participation percentages. CONCLUSIONS: The percentage of smoker participation in
      community-wide stop-smoking contests appears primarily to be a function of total
      resource expenditures, regardless of the specific types of resources funded. Stop
      smoking contests are judged to be quite cost effective. Study strengths and
      weaknesses are discussed.

PMID- 7644454
TI  - Age and smoking cessation behaviors.
AB  - BACKGROUND: Predictors of smoking cessation behaviors during a 3-month period
      were examined among smokers in three age groups: 18 to 29, 30 to 49, and 50 years
      or older. METHODS: Using random-digit dialing, telephone interviews were
      completed with 1,644 smokers in the Chicago metropolitan area at baseline and at
      a 3-month follow-up. Multiple logistic regression was used to identify factors
      that predicted trying to quit smoking and quitting smoking within each age group
      and by stage of readiness to quit smoking. RESULTS: There were no significant
      differences by age in trying to quit smoking or in quitting smoking among smokers
      in the contemplation or preparation stages. However, there were important age
      differences in the factors that predicted those behaviors. In general, different
      factors predicted smoking cessation behaviors in each age group at each of three
      stages of the smoking cessation process (contemplation, preparation, and action).
      Also, within each age group, different factors predicted the behavior at each
      stage. CONCLUSIONS: The findings suggest that smokers of all ages are equally
      appropriate targets for smoking cessation interventions. Moreover, there are
      important age-related differences among smokers over the course of their smoking
      careers that should be considered when planning and implementing smoking
      cessation interventions.

PMID- 7644456
TI  - [Diagnostic value of diffusion in the gas space of the emphysematous lung].

PMID- 7644455
TI  - Dietary saturated and trans fatty acids and cholesterol and 25-year mortality
      from coronary heart disease: the Seven Countries Study.
AB  - BACKGROUND: In the Seven Countries Study associations between intake of
      individual fatty acids and dietary cholesterol were studied in relation to serum
      cholesterol and 25-year mortality from coronary heart disease. All analyses
      concern only intercohort comparisons. METHODS: In the baseline surveys carried
      out between 1958 and 1964, risk factors for coronary heart disease were measured
      among 12,763 middle-aged men constituting 16 cohorts in seven countries. In 1987
      and 1988 equivalent food composites representing the average food intake of each
      cohort at baseline were collected locally and analyzed in a central laboratory.
      The vital status of all participants was verified at regular intervals during 25
      years of follow-up. RESULTS: Of the individual saturated fatty acids, the average
      population intake of lauric and myristic acid was most strongly related to the
      average serum cholesterol level (r > 0.8, P < 0.001). Strong positive
      associations were observed between 25-year death rates from coronary heart
      disease and average intake of the four major saturated fatty acids, lauric,
      myristic, palmitic, and stearic acid (r > 0.8, P < 0.001); the trans fatty acid
      elaidic acid (r = 0.78, P < 0.001); and dietary cholesterol (r = 0.55, P < 0.05).
      CONCLUSIONS: Interpreted in the light of experimental and clinical studies, the
      results of these cross-cultural analyses suggest that dietary saturated and trans
      fatty acids and dietary cholesterol are important determinants of differences in
      population rates of coronary heart disease death.

PMID- 7644457
TI  - [Gold salt alveolitis in 3 patients with rheumatoid arthritis].
AB  - BACKGROUND: When the characteristic symptoms for an interstitial pulmonary
      disease arise in patients with rheumatoid arthritis, a drug-induced alveolitis
      should be considered in the differential diagnosis. In such cases, the
      administration of the drug and gold salts should be stopped. PATIENTS AND
      METHODS: The cases of three patients with rheumatoid arthritis (RA) who had been
      treated with gold salts for 2 months (A), 23 months (B), and 36 months (C) are
      presented. The total dose of sodium aureothiomalate amounted to 280 mg for
      patient A, 1150 mg for patient B, and 2190 mg for patient C. Clinical signs, X
      rays of the lungs, pulmonary function tests, and laboratory tests were evaluated
      for the three patients while, for patient A BAL as well as provocation tests were
      additionally performed before and after therapy. In this case, the histological
      picture of the lungs is presented; biopsies were taken during the first BAL.
      RESULTS: The clinical complaints of all 3 patients were similar, with the
      alveolitis being observed as diffuse in one case and above all in the upper
      regions in two cases on radiology. This led to differing degrees of diffusion
      disorders in the lungs. In patient A, the diagnosis was made in the stage of
      progressive fibrotic alveolitis and was treated with D-penicillamine. All 3
      patients received steroids over 3-6 months and the gold salts were stopped.
      Because of the long duration and doubtful differential diagnosis for patient A
      with either rheumatoid lung or gold salt alveolitis, a provocation test with
      sodium aureothiomalate was performed. All 3 patients had blood eosinophilia
      while, in case A, a thrombopenia was also found. CONCLUSIONS: A gold salt
      alveolitis can occur as a side effect of gold salts in addition to skin
      vasculitis and hematological disorders. When the gold salt administration is not
      stopped a fibrotic alveolitis can develop. The provocation test can be
      diagnostically useful to distinguish between a rheumatoid lung and gold salt
      alveolitis.

PMID- 7644458
TI  - [Induction of rat liver foci by inhaled diisocyanate exposure].
AB  - Diisocyanates are increasingly used for manufacturing polyurethane foam,
      elastomers, adhesives, coatings, insecticides and many other products. The large
      number of workers being exposed to these chemicals has a concentration-dependent
      risk of developing chronic airway disorders. The clinical role of genotoxic
      effects of diisocyanates demonstrable in vivo and in vitro is still unclear just
      as their possible cancerogenic potential. The possible initiating effect of
      diisocyanates in liver carcinogenesis was studied using a rat liver foci bioassay
      (RFLA). The RLFA is based on the histochemical demonstration of foci of
      hepatocytes with altered enzyme equipment, which are induced by carcinogens.
      These foci are generally regarded as early preneoplastic lesions. Rats were
      exposed either to 20 ppb TDI (Toluene diisocyanate) or 20 ppb HDI (Hexamethylene
      diisocyanate) for two hours a day over a period of four weeks. After a break of
      one week the rats received 10 mg Clophen A50/kg body weight as promotor for
      possible isocyanate induced tumorigenic lesions twice a week for eight weeks. For
      positive control the hepatocarcinogen diethylnitrosamin (DEN) was given as a
      single dose of 10 mg and 20 mg. All animals were sacrificed aged 16 weeks. Serial
      cryostat sections were prepared for ATPase and gamma GT staining. The foci number
      was determined and calculated as foci/animal as a mean value taken from both
      staining protocols. Preneoplastic liver foci were observed in positive control
      rats treated with a single dose of 10 mg as well as with 20 mg DEN (4.3 +/- 3.2
      and 1.8 +/- 1.4 respectively). In none of the animals exposed to TDI or HDI
      preneoplastic foci were detectable.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7644459
TI  - [Sarcoidosis in Germany. Analysis of a questionnaire survey in 1992 of patients
      of the German Sarcoidosis Group].
AB  - In 1992, we performed a questionnaire study in patients, who are organized in the
      German Sarcoidosis Self-help group. The aim of our study was to analyze the state
      of diagnosis and therapy of sarcoidosis. In addition, patients were asked for
      their proposals to the physicians. We obtained valid answers from 651 patients. A
      high percentage of incorrect first diagnosis (in 37% as tuberculosis) seemed to
      be dependent on the insufficient use of bronchologic techniques and on the fact
      that in 19% of patients diagnosis was established only by chest x-ray. The
      diagnostic delay was estimated by the difference between the occurrence of the
      first clinical symptoms or x-ray findings and the final diagnosis of sarcoidosis
      and was on average (+/- SD) 2 +/- 5 years. Extrapulmonary manifestations were
      reported in 47% but histologically proven only in 30% of patients. 95% of treated
      patients had cortisone therapy, the median duration of therapy was 3.9 years. 19%
      of the patients underwent so-called alternative therapy concept (mostly
      immunostimulation) after lack of sufficient effect of cortisone treatment on
      symptoms and/or radiologic features. 12% of the patients were not treated at all.
      Familiar associations of sarcoidosis were reported by 49 patients. The patients
      asked for more research, more exchange of information, better education of
      students and physicians on this field and more interdisciplinary contacts.

PMID- 7644460
TI  - [Experimental determination of equivalent percentage changes in measurement
      parameters of dose-response relations with the inhaled methacholine provocation
      test].
AB  - For the experimental determination of equivalent changes of the measurement
      parameters in the non-specific inhalative provocation test with metacholine, 26
      persons with exogenous allergic asthma bronchiale were examined during the
      symptom-free interval. The inhalative provocation test was performed as dose
      response relationship. Linear regressions were calculated with the data obtained.
      The percentage change of the measurement parameters that occurred with a quantity
      of 400 micrograms of aerosolised methacholine was calculated on the basis of the
      regression equation. These changes correspond to equivalent changes of the
      individual measurement parameters compared with each other. Generally, a drop in
      FEV1 by 20% is demanded for a positive provocation test. If this value is defined
      as "gold standard", the measured data allow derivation of the equivalent changes.
      Our studies showed that an increase of Rt by 195% (triplication), a sGaw drop by
      44%, a PEF drop by 20% and a drop of MEF75, MEF50 by 30% each, compared with the
      original value, is equivalent to a significant change in the sense of a positive
      inhalative provocation test.

PMID- 7644461
TI  - [Aspiration of petroleum by a "fire-eater"].
AB  - A 21-year-old man suffered from cough, dyspnoea and hemoptysis following
      accidental aspiration of petroleum. Chest x-ray and computerized tomography one
      day after the aspiration showed infiltrates in the lower fields.
      Fiberbronchoscopy revealed severe bronchitis without any signs of necrosis.
      Flunisolide inhalation (200 micrograms/d) and intravenous application of
      prednisolone (50 mg/d) and clindamycine (600 mg/d) improved pulmonary function
      within a few days. The infiltrates resolved over the following two weeks. This
      favourable result clearly shows that conservative treatment has a role in
      petroleum aspiration.

PMID- 7644462
TI  - Schizophrenia: genetic tools for unraveling the nature of a complex disorder.

PMID- 7644463
TI  - How the plague bacillus and its transmission through fleas were discovered:
      reminiscences from my years at the Pasteur Institute in Paris.

PMID- 7644464
TI  - Schizophrenia susceptibility associated with interstitial deletions of chromosome
      22q11.
AB  - We report the results of two studies examining the genetic overlap between
      schizophrenia and velocardiofacial syndrome. In study A, we characterize two
      interstitial deletions identified on chromosome 22q11 in a sample of
      schizophrenic patients. The size of the deletions was estimated to be between 1.5
      and 2 megabases. In study B, we examine whether variations in deletion size are
      associated with the schizophrenic phenotype in velocardiofacial syndrome
      patients. Our results show that a region of the genome that has been previously
      implicated by genetic linkage analysis can harbor genetic lesions that increase
      the susceptibility to schizophrenia. Our findings should facilitate
      identification and cloning of the schizophrenia susceptibility gene(s) in this
      region and identification of more homogeneous subgroups of patients.

PMID- 7644465
TI  - Cloning of an organic solvent-resistance gene in Escherichia coli: the unexpected
      role of alkylhydroperoxide reductase.
AB  - Although bacterial strain able to grow in the presence of organic solvents have
      been isolated, little is known about the mechanism of their resistance. In the
      present study, 1,2,3,4-tetrahydronaphthalene (tetralin), a solvent with potential
      applications in industrial biocatalysis, was used to select a resistant mutant of
      Escherichia coli. The resultant mutant strain was tested for resistance to a wide
      range of solvents of varying hydrophobicities and was found to be resistant not
      only to tetralin itself but also to cyclohexane, propylbenzene, and 1,2
      dihydronaphthalene. A recombinant library from mutant DNA was used to clone the
      resistance gene. The sequence of the cloned locus was determined and found to
      match the sequence of the previously described alkylhydroperoxide reductase
      operon ahpCF. The mutation was localized to a substitution of valine for glycine
      at position 142 in the coding region of ahpC, which is the gene encoding the
      catalytic subunit of the enzyme. The ahpC mutant was found to have an activity
      that was three times that of the wild type in reducing tetralin hydroperoxide to
      1,2,3,4-tetrahydro-1-naphthol. We conclude that the toxicity of such solvents as
      tetralin is caused by the formation of toxic hydroperoxides in the cell. The ahpC
      mutation increases the activity of the enzyme toward hydrophobic hydroperoxides,
      thereby conferring resistance. The ahpC mutant was sensitive to the more
      hydrophilic solvents xylene and toluene, suggesting that there are additional
      mechanisms of solvent toxicity. Mutants resistant to a mixture of xylene and
      tetralin were isolated from the ahpC mutant but not from the wild-type strain.

PMID- 7644466
TI  - The hepatitis C virus NS3 serine proteinase and NS4A cofactor: establishment of a
      cell-free trans-processing assay.
AB  - The hepatitis C virus RNA genome encodes a long polyprotein that is
      proteolytically processed into at least 10 products. The order of these cleavage
      products in the polyprotein is NH2-C-E1-E2-p7-NS2-NS3-NS4A-NS4B-NS5A-NS5B -COOH.
      A serine proteinase domain located in the N-terminal one-third of nonstructural
      protein NS3 mediates cleavage at four downstream sites (the 3/4A, 4A/4B, 4B/5A,
      and 5A/5B sites). In addition to the proteinase catalytic domain, the NS4A
      protein is required for processing at the 4B/5A site but not at the 5A/5B site.
      These cleavage events are likely to be essential for virus replication, making
      the serine proteinase an attractive antiviral target. Here we describe an in
      vitro assay where the NS3-4A polyprotein, NS3, the serine proteinase domain (the
      N-terminal 181 residues of NS3), and the NS4A cofactor were produced by cell-free
      translation and tested for trans-processing of radiolabeled substrates.
      Polyprotein substrates, NS4A-4B or truncated NS5A-5B, were cleaved in trans by
      all forms of the proteinase, whereas NS4A was also required for NS4B-5A
      processing. Proteolysis was abolished by substitution mutations previously shown
      to inactivate the proteinase or block cleavage at specific sites in vivo.
      Furthermore, N-terminal sequence analysis established that cleavage in vitro
      occurred at the authentic 4A/4B site. Translation in the presence of microsomal
      membranes enhanced processing for some, but not all, proteinase-substrate
      combinations. Trans-processing was both time and temperature dependent and was
      eliminated by treatment with a variety of detergents above their critical micelle
      concentrations. Among many common proteinase inhibitors tested, only high
      (millimolar) concentrations of serine proteinase inhibitors tosyllysyl
      chloromethyl ketone and 4-(2-aminoethyl)benzenesulfonyl fluoride inactivated the
      NS3 proteinase. This in vitro assay should facilitate purification and further
      characterization of the viral serine proteinase and identification of molecules
      which selectively inhibit its activity.

PMID- 7644467
TI  - Origins of the specificity of tissue-type plasminogen activator.
AB  - The role of subsite interactions in defining the stringent substrate specificity
      of tissue-type plasminogen activator (t-PA) has been examined by using an fd
      phage library that displayed random hexapeptide sequences and contained 2 x 10(8)
      independent recombinants. Forty-four individual hexapeptides were isolated and
      identified as improved substrates for t-PA. A peptide containing one of the
      selected amino acid sequences was cleaved by t-PA 5300 times more efficiently
      than a peptide that contained the primary sequence of the actual cleavage site in
      plasminogen. These results suggest that small peptides can mimic determinants
      that mediate specific proteolysis, emphasize the importance of subsite
      interactions in determining protease specificity, and have important implications
      for the evolution of protease cascades.

PMID- 7644468
TI  - Cloning and characterization of a human type II receptor for bone morphogenetic
      proteins.
AB  - Bone morphogenetic proteins (BMPs) are members of the transforming growth factor
      beta superfamily. Several members of this family have been shown to transduce
      their signals through binding to type I and type II serine-(threonine) kinase
      receptors. Here we report the cDNA cloning and characterization of a human type
      II receptor for BMPs (BMPR-II), which is distantly related to DAF-4, a BMP type
      II receptor from Caenorhabditis elegans. In transfected COS-1 cells, osteogenic
      protein (OP)-1/BMP-7, and less efficiently BMP-4, bound to BMPR-II. BMPR-II bound
      ligands only weakly alone, but the binding was facilitated by the presence of
      previously identified type I receptors for BMPs. Binding of OP-1/BMP-7 to BMPR-II
      was also observed in nontransfected cell lines. Moreover, a transcriptional
      activation signal was transduced by BMPR-II in the presence of type I receptors
      after stimulation by OP-1/BMP-7.

PMID- 7644469
TI  - Constitutive phosphorylation of I kappa B alpha by casein kinase II.
AB  - The NF-kappa B/Rel proteins are sequestered in the cytoplasm in association with
      the phosphorylated form of I kappa B alpha. Upon induction with a wide variety of
      agents, the activity of NF-kappa B/Rel proteins is preceded by the rapid
      degradation of I kappa B alpha protein. We report the identification and partial
      purification of a cellular kinase from unstimulated or stimulated murine cells,
      which specifically phosphorylates the C terminus of I kappa B alpha. There are
      several consensus sites for casein kinase II (CKII) in the C-terminal region of I
      kappa B alpha. Additionally, the activity of the cellular kinase is blocked by
      antibodies against the alpha subunit of CKII. No phosphorylation of the C
      terminal region of I kappa B alpha can be detected if the five possible serine
      and threonine residues that can be phosphorylated by CKII are mutated to alanine.
      A two-dimensional tryptic phosphopeptide map of I kappa B alpha from unstimulated
      cells was identical to that obtained by in vitro phosphorylation of I kappa B
      alpha with the partially purified cellular kinase. We propose that constitutive
      phosphorylation of I kappa B alpha is carried out by CKII.

PMID- 7644470
TI  - A yeast gene required for DNA replication encodes a protein with homology to DNA
      helicases.
AB  - A yeast gene has been identified by screening for DNA replication mutants using a
      permeabilized cell replication assay. The mutant is temperature sensitive for
      growth and shows a cell cycle phenotype typical of DNA replication mutants. RNA
      synthesis is normal in the mutant but DNA synthesis ceases upon shift to the
      nonpermissive temperature. The DNA2 gene was cloned by complementation of the
      dna2ts gene phenotype. The gene is essential for viability. The gene encodes a
      172-kDa protein with characteristic DNA helicase motifs. A hemagglutinin epitope
      Dna2 fusion protein was prepared and purified by conventional and immunoaffinity
      chromatography. The purified protein is a DNA-dependent ATPase and has 3' to 5'
      DNA helicase activity specific for forked substrates. A nuclease activity that
      endonucleolytically cleaves DNA molecules having a single-stranded 5' tail
      adjacent to a duplex region copurifies through all steps with the fusion protein.

PMID- 7644471
TI  - The yeast nuclear import receptor is required for mitosis.
AB  - The nuclear import system is highly conserved among eukaryotes. Here we report
      the effects of a conditional mutation in SRP1, which encodes a Saccharomyces
      cerevisiae homolog of the vertebrate nuclear import receptor importin. Importin
      was isolated as a factor required for the initial targeting step of a nuclear
      import substrate to the nuclear envelope in a mammalian in vitro assay. We show
      that yeast Srp1 is similarly required for protein import. In addition, Srp1 is
      also required for the execution of mitosis: we demonstrate that cells containing
      a conditional mutation of SRP1 arrest with a G2/M phenotype in a manner analogous
      to classic cdc mutants. This defect may be due to the failure of the mutant to
      degrade the mitotic cyclin Clb2 and other proteins required for mitosis. The
      requirement of a nuclear import receptor for cell cycle-regulated proteolysis
      implies that import of cell cycle regulators into the nucleus is critical for
      cell cycle progression.

PMID- 7644472
TI  - Role of essential light chain EF hand domains in calcium binding and regulation
      of scallop myosin.
AB  - The specific Ca2+ binding site that triggers contraction of molluscan muscle
      requires the presence of an essential light chain (ELC) from a Ca2+ binding
      myosin. Of the four EF hand-like domains in molluscan ELCs, only domain III has
      an amino acid sequence predicted to be capable of binding Ca2+. In this report,
      we have used mutant ELCs to locate the Ca2+ binding site in scallop myosin and to
      probe the role of the ELC in regulation. Point mutations in domain III of scallop
      ELC have no effect on Ca2+ binding. Interestingly, scallop and rat cardiac ELC
      chimeras support Ca2+ binding only if domain I is scallop. These results are
      nevertheless in agreement with structural studies on a proteolytic fragment of
      scallop myosin, the regulatory domain. Furthermore, Ca2+ sensitivity of the
      scallop myosin ATPase requires scallop ELC domain I: ELCs containing cardiac
      domain I convert scallop myosin to an unregulated molecule whose activity is no
      longer repressed in the absence of Ca2+. Despite its unusual EF hand domain
      sequence, our data indicate that the unique and required contribution of
      molluscan ELCs to Ca2+ binding and regulation of molluscan myosins resides
      exclusively in domain I.

PMID- 7644473
TI  - The role of cysteine proteases in hypoxia-induced rat renal proximal tubular
      injury.
AB  - The role of the lysosomal proteases cathepsins B and L and the calcium-dependent
      cytosolic protease calpain in hypoxia-induced renal proximal tubular injury was
      investigated. As compared to normoxic tubules, cathepsin B and L activity,
      evaluated by the specific fluorescent substrate benzyloxycarbonyl-L-phenylalanyl
      L-arginine-7-amido-4-methylcoumarin, was not increased in hypoxic tubules or the
      medium used for incubation of hypoxic tubules in spite of high lactate
      dehydrogenase (LDH) release into the medium during hypoxia. These data in rat
      proximal tubules suggest that cathepsins are not released from lysosomes and do
      not gain access to the medium during hypoxia. An assay for calpain activity in
      isolated proximal tubules using the fluorescent substrate N-succinyl-Leu-Tyr-7
      amido-4-methylcoumarin was developed. The calcium ionophore ionomycin induced a
      dose-dependent increase in calpain activity. This increase in calpain activity
      occurred prior to cell membrane damage as assessed by LDH release. Tubular
      calpain activity increased significantly by 7.5 min of hypoxia, before there was
      significant LDH release, and further increased during 20 min of hypoxia. The
      cysteine protease inhibitor N-benzyloxycarbonyl-Val-Phe methyl ester (CBZ)
      markedly decreased LDH release after 20 min of hypoxia and completely prevented
      the increase in calpain activity during hypoxia. The increase in calpain activity
      during hypoxia and the inhibitor studies with CBZ therefore supported a role for
      calpain as a mediator of hypoxia-induced proximal tubular injury.

PMID- 7644474
TI  - 7-Chloro-3-methyl-3,4-dihydro-2H-1,2,4-benzothiadiazine S,S-dioxide (IDRA 21), a
      congener of aniracetam, potently abates pharmacologically induced cognitive
      impairments in patas monkeys.
AB  - We report here on the ability of IDRA 21 and aniracetam, two negative allosteric
      modulators of glutamate-induced DL-alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid (AMPA) receptor desensitization, to attenuate alprazolam
      induced learning deficit in patas monkeys working in a complex behavioral task.
      In one component of a multiple schedule (repeated acquisition or "learning"),
      patas monkeys acquired a different four-response chain each session by responding
      sequentially on three keys in the presence of four discriminative stimuli
      (geometric forms or numerals). In the other component (performance) the four
      response chain was the same each session. The response chain in each component
      was maintained by food presentation under a fixed-ratio schedule. When alprazolam
      (0.1 or 0.32 mg/kg p.o.) was administered alone, this full allosteric modulator
      of gamma-aminobutyric acid type A (GABAA) receptors produced large decreases in
      the response rate and accuracy in the learning component of the task. IDRA 21 (3
      or 5.6 mg/kg p.o.) and aniracetam (30 mg/kg p.o.) administered 60 min before
      alprazolam, having no effect when given alone, antagonized the large disruptive
      effects of alprazolam on learning. From dose-response studies, it can be
      estimated that IDRA 21 is approximately 10-fold more potent than aniracetam in
      antagonizing alprazolam-induced learning deficit. We conclude that IDRA 21, a
      chemically unrelated pharmacological congener of aniracetam, improves learning
      deficit induced in patas monkeys by the increase of GABAergic tone elicited by
      alprazolam. Very likely IDRA 21 exerts its behavioral effects by antagonizing
      AMPA receptor desensitization.

PMID- 7644475
TI  - Identification of a plant serine-arginine-rich protein similar to the mammalian
      splicing factor SF2/ASF.
AB  - We show that the higher plant Arabidopsis thaliana has a serine-arginine-rich
      (SR) protein family whose members contain a phosphoepitope shared by the animal
      SR family of splicing factors. In addition, we report the cloning and
      characterization of a cDNA encoding a higher-plant SR protein from Arabidopsis,
      SR1, which has striking sequence and structural homology to the human splicing
      factor SF2/ASF. Similar to SF2/ASF, the plant SR1 protein promotes splice site
      switching in mammalian nuclear extracts. A novel feature of the Arabidopsis SR
      protein is a C-terminal domain containing a high concentration of proline,
      serine, and lysine residues (PSK domain), a composition reminiscent of histones.
      This domain includes a putative phosphorylation site for the mitotic kinase
      cyclin/p34cdc2.

PMID- 7644476
TI  - A single GAL4 dimer can maximally activate transcription under physiological
      conditions.
AB  - Most eukaryotic promoters contain multiple binding sites for one or more
      transcriptional activators that interact in a synergistic manner. A common view
      is that synergism is a manifestation of the need for many contacts between
      activators and the general transcription machinery that a single activator
      presumably cannot fulfill. In this model, various combinations of protein-protein
      interactions control the level of gene expression. However, we show here that
      under physiological conditions, a single binding site and presumably GAL4 can
      activate transcription to the maximum possible level in vivo. Synergistic effects
      in this natural system are shown to be consistent with cooperative DNA binding.
      These results point to DNA occupancy as the major element in fine tuning gene
      expression in the galactose regulon.

PMID- 7644477
TI  - A synthetic inhibitor of the mitogen-activated protein kinase cascade.
AB  - Treatment of cells with a variety of growth factors triggers a phosphorylation
      cascade that leads to activation of mitogen-activated protein kinases (MAPKs,
      also called extracellular signal-regulated kinases, or ERKs). We have identified
      a synthetic inhibitor of the MAPK pathway. PD 098059 [2-(2'-amino-3'
      methoxyphenyl)-oxanaphthalen-4-one] selectively inhibited the MAPK-activating
      enzyme, MAPK/ERK kinase (MEK), without significant inhibitory activity of MAPK
      itself. Inhibition of MEK by PD 098059 prevented activation of MAPK and
      subsequent phosphorylation of MAPK substrates both in vitro and in intact cells.
      Moreover, PD 098059 inhibited stimulation of cell growth and reversed the
      phenotype of ras-transformed BALB 3T3 mouse fibroblasts and rat kidney cells.
      These results indicate that the MAPK pathway is essential for growth and
      maintenance of the ras-transformed phenotype. Further, PD 098059 is an invaluable
      tool that will help elucidate the role of the MAPK cascade in a variety of
      biological settings.

PMID- 7644478
TI  - Role of glutathione in the export of compounds from cells by the multidrug
      resistance-associated protein.
AB  - Multidrug-resistance-associated protein (MRP) is a plasma membrane glycoprotein
      that can confer multidrug resistance (MDR) by lowering intracellular drug
      concentration. Here we demonstrate that depletion of intracellular glutathione by
      DL-buthionine (S,R)-sulfoximine results in a complete reversal of resistance to
      doxorubicin, daunorubicin, vincristine, and VP-16 in lung carcinoma cells
      transfected with a MRP cDNA expression vector. Glutathione depletion had less
      effect on MDR in cells transfected with MDR1 cDNA encoding P-glycoprotein and did
      not increase the passive uptake of daunorubicin by cells, indicating that the
      decrease of MRP-mediated MDR was not due to nonspecific membrane damage.
      Glutathione depletion resulted in a decreased efflux of daunorubicin from MRP
      transfected cells, but not from MDR1-transfected cells, suggesting that
      glutathione is specifically required for the export of drugs from cells by MRP.
      We also show that MRP increases the export of glutathione from the cell and this
      increased export is further elevated in the presence of arsenite. Our results
      support the hypothesis that MRP functions as a glutathione S-conjugate carrier.

PMID- 7644479
TI  - Phenotype correction in retinal pigment epithelium in murine
      mucopolysaccharidosis VII by adenovirus-mediated gene transfer.
AB  - We have studied the use of adenovirus-mediated gene transfer to reverse the
      pathologic changes of lysosomal storage disease caused by beta-glucuronidase
      deficiency in the eyes of mice with mucopolysaccharidosis VII. A recombinant
      adenovirus carrying the human beta-glucuronidase cDNA coding region under the
      control of a non-tissue-specific promoter was injected intravitreally or
      subretinally into the eyes of mice with mucopolysaccharidosis VII. At 1-3 weeks
      after injection, the treated and control eyes were examined histochemically for
      beta-glucuronidase expression and histologically for phenotypic correction of the
      lysosomal storage defect. Enzymatic expression was detected 1-3 weeks after
      injection. Storage vacuoles in the retinal pigment epithelium (RPE) were still
      present 1 week after gene transfer but were reduced to undetectable levels by 3
      weeks in both intravitreally and subretinally injected eyes. There was minimal
      evidence of ocular pathology associated with the viral injection. These data
      indicate that adenovirus-mediated gene transfer to the eye may provide for
      adjunctive therapy for lysosomal storage diseases affecting the RPE in
      conjunction with enzyme replacement and/or gene therapies for correction of
      systemic disease manifestations. The data also support the view that recombinant
      adenovirus may be useful as a gene therapy vector for retinal degenerations that
      result from a primary genetic defect in the RPE cells.

PMID- 7644480
TI  - Electrocatalytically driven omega-hydroxylation of fatty acids using cytochrome
      P450 4A1.
AB  - The cyclic enzymatic function of a cytochrome P450, as it catalyzes the oxygen
      dependent metabolism of many organic chemicals, requires the delivery of two
      electrons to the hemeprotein. In general these electrons are transferred from
      NADPH to the P450 via an FMN- and FAD-containing flavoprotein (NADPH-P450
      reductase). The present paper shows that NADPH can be replaced by an
      electrochemically generated reductant [cobalt(II) sepulchrate trichloride] for
      the electrocatalytically driven omega-hydroxylation of lauric acid. Results are
      presented illustrating the use of purified recombinant proteins containing P450
      4A1, such as the fusion protein (rFP450 [mRat4A1/mRatOR]L1) or a system
      reconstituted with purified P450 4A1 plus purified NADPH-P450 reductase. Rates of
      formation of 12-hydroxydodecanoic acid by the electrochemical method are
      comparable to those obtained using NADPH as electron donor. These results suggest
      the practicality of developing electrocatalytically dependent bioreactors
      containing different P450s as catalysts for the large-scale synthesis of stereo-
      and regio-selective hydroxylation products of many chemicals.

PMID- 7644481
TI  - Selenophosphate synthetase: detection in extracts of rat tissues by immunoblot
      assay and partial purification of the enzyme from the archaean Methanococcus
      vannielii.
AB  - In Escherichia coli and Salmonella typhimurium it has been shown that
      selenophosphate serves as the selenium donor for the conversion of seryl-tRNA to
      selenocysteyl-tRNA and for the synthesis of 2-selenouridine, a modified
      nucleoside present in tRNAs. Although selenocysteyl-tRNA also is formed in
      eukaryotes and is used for the specific insertion of selenocysteine into
      proteins, the precise mechanism of its biosynthesis from seryl-tRNA in these
      systems is not known. Because selenophosphate is extremely oxygen labile and
      difficult to identify in biological systems, we used an immunological approach to
      detect the possible presence of selenophosphate synthetase in mammalian tissues.
      With antibodies elicited to E. coli selenophosphate synthetase the enzyme was
      detected in extracts of rat brain, liver, kidney, and lung by immunoblotting.
      Especially high levels were detected in Methanococcus vannielii, a member of the
      domain Archaea, and the enzyme was partially purified from this source. It seems
      likely that the use of selenophosphate as a selenium donor is widespread in
      biological systems.

PMID- 7644483
TI  - Rapid genome change in synthetic polyploids of Brassica and its implications for
      polyploid evolution.
AB  - Although the evolutionary success of polyploidy in higher plants has been widely
      recognized, there is virtually no information on how polyploid genomes have
      evolved after their formation. In this report, we used synthetic polyploids of
      Brassica as a model system to study genome evolution in the early generations
      after polyploidization. The initial polyploids we developed were completely
      homozygous, and thus, no nuclear genome changes were expected in self-fertilized
      progenies. However, extensive genome change was detected by 89 nuclear DNA clones
      used as probes. Most genome changes involved loss and/or gain of parental
      restriction fragments and appearance of novel fragments. Genome changes occurred
      in each generation from F2 to F5, and the frequency of change was associated with
      divergence of the diploid parental genomes. Genetic divergence among the
      derivatives of synthetic polyploids was evident from variation in genome
      composition and phenotypes. Directional genome changes, possibly influenced by
      cytoplasmic-nuclear interactions, were observed in one pair of reciprocal
      synthetics. Our results demonstrate that polyploid species can generate extensive
      genetic diversity in a short period of time. The occurrence and impact of this
      process in the evolution of natural polyploids is unknown, but it may have
      contributed to the success and diversification of many polyploid lineages in both
      plants and animals.

PMID- 7644482
TI  - Eukaryotic methionyl aminopeptidases: two classes of cobalt-dependent enzymes.
AB  - Using partial amino acid sequence data derived from porcine methionyl
      aminopeptidase (MetAP; methionine aminopeptidase, peptidase M; EC 3.4.11.18), a
      full-length clone of the homologous human enzyme has been obtained. The cDNA
      sequence contains 2569 nt with a single open reading frame corresponding to a
      protein of 478 amino acids. The C-terminal portion representing the catalytic
      domain shows limited identity with MetAP sequences from various prokaryotes and
      yeast, while the N terminus is rich in charged amino acids, including extended
      strings of basic and acidic residues. These highly polar stretches likely result
      in the spuriously high observed molecular mass (67 kDa). This cDNA sequence is
      highly similar to a rat protein, termed p67, which was identified as an inhibitor
      of phosphorylation of initiation factor eIF2 alpha and was previously predicted
      to be a metallopeptidase based on limited sequence homology. Model building
      established that human MetAP (p67) could be readily accommodated into the
      Escherichia coli MetAP structure and that the Co2+ ligands were fully preserved.
      However, human MetAP was found to be much more similar to a yeast open reading
      frame that differed markedly from the previously reported yeast MetAP. A similar
      partial sequence from Methanothermus fervidus suggests that this p67-like
      sequence is also found in prokaryotes. These findings suggest that there are two
      cobalt-dependent MetAP families, presently composed of the prokaryote and yeast
      sequences (and represented by the E. coli structure) (type I), on the one hand,
      and by human MetAP, the yeast open reading frame, and the partial prokaryotic
      sequence (type II), on the other.

PMID- 7644484
TI  - Rat growth hormone gene introns stimulate nucleosome alignment in vitro and in
      transgenic mice.
AB  - Average hepatic expression (mRNA per cell per gene) of a metallothionein-rat
      growth hormone (rGH) gene with its natural introns was about 15-fold higher than
      an intronless version when tested in transgenic mice. We examined the idea that
      intron removal leads to an alteration in chromatin structure that might be
      responsible for this effect. Using an in vitro chromatin assembly system, we
      observed that nucleosomes were aligned in a characteristic ordered array over the
      gene and promoter when all introns were present. Linker histones were necessary
      for this alignment to occur. In contrast, nucleosome alignment was perturbed in
      constructs lacking some or all of the introns. A similar disruption of nucleosome
      alignment was observed when comparing chromatin from livers of transgenic mice
      carrying rGH transgenes with or without introns. In vitro, sequences at the 3'
      end of the rGH gene position nucleosomes and facilitate nucleosome alignment
      upstream; however, nucleosome alignment does not occur on the approximately 3 kb
      of downstream flanking rat sequence. These observations suggest that signals
      present in genomic rGH DNA may serve to establish appropriate nucleosome
      alignment during development and, possibly, to restore nucleosome alignment to
      the transcribed region after disruption incurred by the passage of an RNA
      polymerase molecule, thereby facilitating subsequent rounds of transcription.

PMID- 7644485
TI  - Lith1, a major gene affecting cholesterol gallstone formation among inbred
      strains of mice.
AB  - The prevalence of cholesterol gallstones differs among inbred strains of mice fed
      a diet containing 15% (wt/wt) dairy fat, 1% (wt/wt) cholesterol, and 0.5% (wt/wt)
      cholic acid. Strains C57L, SWR, and A were notable for a high prevalence of
      cholelithiasis; strains C57BL/6, C3H, and SJL had an intermediate prevalence; and
      strains SM, AKR, and DBA/2 exhibited no cholelithiasis after consuming the diet
      for 18 weeks. Genetic analysis of the difference in gallstone prevalence rates
      between strains AKR and C57L was carried out by using the AKXL recombinant inbred
      strain set and (AKR x C57L)F1 x AKR backcross mice. Susceptibility to gallstone
      formation was found to be a dominant trait determined by at least two genes. A
      major gene, named Lith1, mapped to mouse chromosome 2. When examined after 6
      weeks on the lithogenic diet, the activity of hepatic 3-hydroxy-3-methylglutaryl
      CoA reductase (EC 1.1.1.88) was downregulated as expected in the gallstone
      resistant strains, AKR and SJL, but this enzyme failed to downregulate in C57L
      and SWR, the gallstone-susceptible strains. This suggests that regulation of the
      rate-limiting enzyme in cholesterol biosynthesis may be pivotal in determining
      the occurrence and severity of cholesterol hypersecretion and hence lithogenicity
      of gallbladder bile. These studies indicate that genetic factors are critical in
      determining gallstone formation and that the genetic resources of the mouse model
      may permit these factors to be identified.

PMID- 7644486
TI  - Neoplastic development: paradoxical relation between impaired cell growth at low
      population density and excessive growth at high density.
AB  - The role of heritable, population-wide cell damage in neoplastic development was
      studied in the 28 L subline of NIH 3T3 cells. These cells differ from the 17(3c)
      subline used previously for such studies in their lower frequency of
      "spontaneous" transformation at high population density and their greater
      capacity to produce large, dense transformed foci. Three cultures of the 28 L
      subline of NIH 3T3 cells were held under the constraint of confluence for 5 wk (5
      wk 1 degree assay) and then assayed twice in succession (2 degrees and 3 degrees
      assays) for transformed foci and saturation density. After the 2 degrees assay,
      the cells were also passaged at low density to determine their exponential growth
      rates and cloned to determine the size and morphological features of the
      colonies. Concurrent measurements were made in each case with control cells that
      had been kept only in frequent low-density passages and cells that had been kept
      at confluence for only 2 wk (2 wk 1 degree). Two of the three cultures
      transferred from the 2 degrees assay of the 5 wk 1 degree cultures produced light
      transformed foci, and the third produced dense foci. The light focus-forming
      cultures grew to twice the control saturation density in their 2 degrees assay
      and 6-8 times the control density in the 3 degrees assay; saturation densities
      for the dense focus formers were about 10 times the control values in both
      assays. All three of the cultures transferred from the 2 degrees assay of the 5
      wk 1 degree cultures multiplied at lower rates than controls at low densities,
      but the dense focus formers multiplied faster than the light focus formers. The
      reduced rates of multiplication of the light focus formers persisted for > 50
      generations of exponential multiplication at low densities. Isolated colonies
      formed from single cells of the light focus formers were of a lower population
      density than controls; colonies formed by the dense focus formers were slightly
      denser than the controls but occupied only half the area. A much higher
      proportion of the colonies from the 5 wk 1 degree cultures than the controls
      consisted of giant cells or mixtures of giant and normal-appearing cells. The
      results reinforce the previous conclusion that the early increases in saturation
      density and light focus formation are associated with, and perhaps caused by,
      heritable, population-wide damage to cells that is essentially epigenetic in
      nature. The more advanced transformation characterized by large increases in
      saturation density and dense focus formation could have originated from rare
      genetic changes, such as chromosome rearrangements, known to occur at an elevated
      frequency in cells destabilized by antecedent cellular damage.

PMID- 7644487
TI  - High-efficiency retroviral-mediated gene transfer into human and nonhuman primate
      peripheral blood lymphocytes.
AB  - Peripheral blood lymphocytes (PBLs) are primary targets for gene therapy of
      inherited and acquired disorders of the immune system. We describe the
      development of an optimized transduction system that provides for high-efficiency
      retrovirus-mediated gene transfer into primary PBLs. This optimized transduction
      protocol combines centrifugation of the lymphocytes (1000 x g) at the inception
      of transduction with phosphate depletion, low-temperature incubation (32 degrees
      C), and the use of the packaging cell line PG13. Gene marking studies of human
      and primate PBLs using these optimized transduction conditions demonstrated that
      the transduction efficiency exceeded 50% of the total lymphocyte population. The
      optimized transduction efficiency of PBLs with amphotropic retroviral vectors was
      in excess of 25%. The transduction procedure does not alter phenotype, viability,
      or expansion of the transduced cells. Our data indicate that this optimized
      transduction system leads to high-efficiency gene transfer into primary human
      lymphocytes, which obviates the requirement for selection of transduced cells
      prior to gene-therapy procedures. Thus, large quantities of healthy retrovirally
      transduced lymphocytes containing a broad immunological repertoire can be
      generated for use in clinical protocols. Our results represent a significant
      improvement in the methodology for the transduction of lymphocytes for gene
      therapy.

PMID- 7644488
TI  - Modulation of pair bonding in female prairie voles (Microtus ochrogaster) by
      corticosterone.
AB  - Glucocorticoid levels in animals may respond to and influence the development of
      social attachments. This hypothesis was tested in prairie voles (Microtus
      ochrogaster), monogamous rodents that form long-term heterosexual pair bonds. In
      socially naive female prairie voles, cohabitation with an unfamiliar male
      resulted in a dramatic decline in serum corticosterone levels. When
      corticosterone levels were reduced via adrenalectomy, females developed partner
      preferences after 1 h of cohabitation, while sham-operated and untreated females
      required 3 h or more of nonsexual cohabitation to establish a partner preference.
      In adrenalectomized and intact females, exogenous injections of corticosterone,
      given prior to social exposure, prevented the development of preferences for the
      cohabitating male. Although corticosterone inhibited the development of partner
      preferences, it did not interfere with the expression of previously established
      social preferences. These results suggest that social stimuli can modulate
      adrenal activity and that adrenal activity, in turn, is capable of influencing
      the formation of adult social preferences in female prairie voles. The
      involvement of the adrenal axis in the formation of partner preferences and the
      subsequent development of pair bonds provides a mechanism through which
      environmental and social factors may influence social organization in this
      species.

PMID- 7644489
TI  - Benzodiazepine-insensitive mice generated by targeted disruption of the gamma 2
      subunit gene of gamma-aminobutyric acid type A receptors.
AB  - Vigilance, anxiety, epileptic activity, and muscle tone can be modulated by drugs
      acting at the benzodiazepine (BZ) site of gamma-aminobutyric acid type A (GABAA)
      receptors. In vivo, BZ sites are potential targets for endogenous ligands
      regulating the corresponding central nervous system states. To assess the
      physiological relevance of BZ sites, mice were generated containing GABAA
      receptors devoid of BZ sites. Following targeted disruption of the gamma 2
      subunit gene, 94% of the BZ sites were absent in brain of neonatal mice, while
      the number of GABA sites was only slightly reduced. Except for the gamma 2
      subunit, the level of expression and the regional and cellular distribution of
      the major GABAA receptor subunits were unaltered. The single channel main
      conductance level and the Hill coefficient were reduced to values consistent with
      recombinant GABAA receptors composed of alpha and beta subunits. The GABA
      response was potentiated by pentobarbital but not by flunitrazepam. Diazepam was
      inactive behaviorally. Thus, the gamma 2 subunit is dispensable for the assembly
      of functional GABAA receptors but is required for normal channel conductance and
      the formation of BZ sites in vivo. BZ sites are not essential for embryonic
      development, as suggested by the normal body weight and histology of newborn
      mice. Postnatally, however, the reduced GABAA receptor function is associated
      with retarded growth, sensorimotor dysfunction, and drastically reduced life
      span. The lack of postnatal GABAA receptor regulation by endogenous ligands of BZ
      sites might contribute to this phenotype.

PMID- 7644490
TI  - The rat suprachiasmatic nucleus is a clock for all seasons.
AB  - Seasonal changes of daylength (photoperiod) affect the expression of hormonal and
      behavioral circadian rhythms in a variety of organisms. In mammals, such effects
      might reflect photoperiodic changes in the circadian pace-making system [located
      in the suprachiasmatic nucleus (SCN) of the hypothalamus] that governs these
      rhythms, but to date no functionally relevant, intrinsic property of the SCN has
      been shown to be photoperiod dependent. We have analyzed the temporal regulation
      of light-induced c-fos gene expression in the SCN of rats maintained in long or
      short photoperiods. Both in situ hybridization and immunohistochemical assays
      show that the endogenous circadian rhythm of light responsiveness in the SCN is
      altered by photoperiod, with the duration of the photosensitive subjective night
      under the short photoperiod 5-6 h longer than under the long photoperiod. Our
      results provide evidence that a functional property of the SCN is altered by
      photoperiod and suggest that the nucleus is involved in photoperiodic time
      measurement.

PMID- 7644491
TI  - Polymorphic simple sequence repeat regions in chloroplast genomes: applications
      to the population genetics of pines.
AB  - Simple sequence repeats (SSRs), consisting of tandemly repeated multiple copies
      of mono-, di-, tri-, or tetranucleotide motifs, are ubiquitous in eukaryotic
      genomes and are frequently used as genetic markers, taking advantage of their
      length polymorphism. We have examined the polymorphism of such sequences in the
      chloroplast genomes of plants, by using a PCR-based assay. GenBank searches
      identified the presence of several (dA)n.(dT)n mononucleotide stretches in
      chloroplast genomes. A chloroplast (cp) SSR was identified in three pine species
      (Pinus contorta, Pinus sylvestris, and Pinus thunbergii) 312 bp upstream of the
      psbA gene. DNA amplification of this repeated region from 11 pine species
      identified nine length variants. The polymorphic amplified fragments were
      isolated and the DNA sequence was determined, confirming that the length
      polymorphism was caused by variation in the length of the repeated region. In the
      pines, the chloroplast genome is transmitted through pollen and this PCR assay
      may be used to monitor gene flow in this genus. Analysis of 305 individuals from
      seven populations of Pinus leucodermis Ant. revealed the presence of four
      variants with intrapopulational diversities ranging from 0.000 to 0.629 and an
      average of 0.320. Restriction fragment length polymorphism analysis of cpDNA on
      the same populations previously failed to detect any variation. Population
      subdivision based on cpSSR was higher (Gst = 0.22, where Gst is coefficient of
      gene differentiation) than that revealed in a previous isozyme study (Gst =
      0.05). We anticipate that SSR loci within the chloroplast genome should provide a
      highly informative assay for the analysis of the genetic structure of plant
      populations.

PMID- 7644492
TI  - Proenzyme of Manduca sexta phenol oxidase: purification, activation, substrate
      specificity of the active enzyme, and molecular cloning.
AB  - Phenol oxidase (PO) was isolated as a proenzyme (pro-phenol oxidase, pro-PO) from
      the hemolymph of Manduca sexta larvae and purified to homogeneity. Pro-PO
      exhibits a M(r) of 130,000 on gel filtration and two bands with an apparent M(r)
      of approximately 100,000 on SDS/PAGE, as well as size-exclusion HPLC. Activation
      of pro-PO was achieved either by specific proteolysis by a cuticular protease or
      by the detergent cetylpyridinium chloride at a concentration below the critical
      micellar concentration. A cDNA clone for M. sexta pro-PO was obtained from a
      larval hemocyte cDNA library. The clone encodes a polypeptide of approximately
      80,000 Da that contains two copper-binding sites and shows high sequence
      similarity to POs, hemocyanins, and storage proteins of arthropods. The M. Sexta
      pro-PO, together with other arthropod pro-POs, contains a short stretch of amino
      acids with sequence similarity to the thiol ester region of alpha-macroglobulins
      and complement proteins C3 and C4.

PMID- 7644493
TI  - Nucleotide sequence of the cDNA encoding the proenzyme of phenol oxidase A1 of
      Drosophila melanogaster.
AB  - Clones encoding pro-phenol oxidase [pro-PO; zymogen of phenol oxidase
      (monophenol, L-dopa:oxygen oxidoreductase, EC 1.14.18.1)] A1 were isolated from a
      lambda gt10 library that originated from Drosophila melanogaster strain Oregon-R
      male adults. The 2294 bp of the cDNA included a 13-bp 5'-noncoding region, a 2070
      bp encoding open reading frame of 690 amino acids, and a 211-bp 3'-noncoding
      region. A hydrophobic NH2-terminal sequence for a signal peptide is absent in the
      protein. Furthermore, there are six potential N-glycosylation sites in the
      sequence, but no amino sugar was detected in the purified protein by amino acid
      analysis, indicating the lack of an N-linked sugar chain. The potential copper
      binding sites, amino acids 200-248 and 359-414, are highly homologous to the
      corresponding sites of hemocyanin of the tarantula Eurypelma californicum, the
      horseshoe crab Limulus polyphemus, and the spiny lobster Panulirus interruptus.
      On the basis of the phylogenetic tree constructed by the neighbor-joining method,
      vertebrate tyrosinases and molluscan hemocyanins constitute one family, whereas
      pro-POs and arthropod hemocyanins group with another family. It seems, therefore,
      likely that pro-PO originates from a common ancestor with arthropod hemocyanins,
      independently to the vertebrate and microbial tyrosinases.

PMID- 7644494
TI  - Molecular cloning of insect pro-phenol oxidase: a copper-containing protein
      homologous to arthropod hemocyanin.
AB  - Pro-phenol oxidase [pro-PO; zymogen of phenol oxidase (monophenol, L-dopa:oxygen
      oxidoreductase, EC 1.14.18.1)] is present in the hemolymph plasma of the silkworm
      Bombyx mori. Pro-PO is a heterodimeric protein synthesized by hemocytes. A
      specific serine proteinase activates both subunits through a limited proteolysis.
      The amino acid sequences of both subunits were deduced from their respective
      cDNAs; amino acid sequence homology between the subunits was 51%. The deduced
      amino acid sequences revealed domains highly homologous to the copper-binding
      site sequences (copper-binding sites A and B) of arthropod hemocyanins. The
      overall sequence homology between silkworm pro-PO and arthropod hemocyanins
      ranged from 29 to 39%. Phenol oxidases from prokaryotes, fungi, and vertebrates
      have sequences homologous to only the copper-binding site B of arthropod
      hemocyanins. Thus, silkworm pro-PO DNA described here appears distinctive and
      more closely related to arthropod hemocyanins. The pro-PO-activating serine
      proteinase was shown to hydrolyze peptide bonds at the carboxyl side of arginine
      in the sequence-Asn-49-Arg-50-Phe-51-Gly-52- of both subunits. Amino groups of N
      termini of both subunits were indicated to be N-acetylated. The cDNAs of both pro
      PO subunits lacked signal peptide sequences. This result supports our contention
      that mature pro-PO accumulates in the cytoplasm of hemocytes and is released by
      cell rupture, as for arthropod hemocyanins.

PMID- 7644495
TI  - Targeted disruption of the surfactant protein B gene disrupts surfactant
      homeostasis, causing respiratory failure in newborn mice.
AB  - Surfactant protein B (SP-B) is an 8.7-kDa, hydrophobic protein that enhances the
      spreading and stability of surfactant phospholipids in the alveolus. To further
      assess the role of SP-B in lung function, the SP-B gene was disrupted by
      homologous recombination in murine mouse embryonic stem cells. Mice with a single
      mutated SP-B allele (+/-) were unaffected, whereas homozygous SP-B -/- offspring
      died of respiratory failure immediately after birth. Lungs of SP-B -/- mice
      developed normally but remained atelectatic in spite of postnatal respiratory
      efforts. SP-B protein and mRNA were undetectable and tubular myelin figures were
      lacking in SP-B -/- mice. Type II cells of SP-B -/- mice contained no fully
      formed lamellar bodies. While the abundance of SP-A and SP-C mRNAs was not
      altered, an aberrant form of pro-SP-C, 8.5 kDa, was detected, and fully processed
      SP-C peptide was markedly decreased in lung homogenates of SP-B -/- mice.
      Ablation of the SP-B gene disrupts the routing, storage, and function of
      surfactant phospholipids and proteins, causing respiratory failure at birth.

PMID- 7644496
TI  - A potent inhibitor of endothelial cell proliferation is generated by proteolytic
      cleavage of the chemokine platelet factor 4.
AB  - Platelet factor 4 (PF-4) is an archetype of the "chemokine" family of low
      molecular weight proteins that play an important role in injury responses and
      inflammation. From activated human leukocyte culture supernatants, we have
      isolated a form of PF-4 that acts as a potent inhibitor of endothelial cell
      proliferation. The PF-4 derivative is generated by peptide bond cleavage between
      Thr-16 and Ser-17, a site located downstream from the highly conserved and
      structurally important CXC motif. The unique cleavage leads to a loss of one of
      the structurally important large loops in the PF-4 molecule and generation of an
      N terminus with basic residues that have the potential to interact with the
      acidic extracellular domain of the G-protein-coupled chemokine receptor. The N
      terminal processed PF-4 exhibited a 30- to 50-fold greater growth inhibitory
      activity on endothelial cells than PF-4. Since endothelial cell growth inhibition
      is the only known cellular activity of the cleaved PF-4, we have designated this
      chemokine endothelial cell growth inhibitor. The N-terminal processing of PF-4
      may represent an important mechanism for modulating PF-4 activity on endothelial
      cells during tissue injury, inflammation, and neoplasia.

PMID- 7644497
TI  - The two single-strand cleavages at each end of Tn10 occur in a specific order
      during transposition.
AB  - During Tn10 transposition, the element is excised from the donor site by double
      strand cleavages at the two transposon ends. Double-strand cleavage is a central
      step in the nonreplicative transposition reaction of many transposons in both
      prokaryotes and eukaryotes. Evidence is presented to show that the Tn10 double
      strand cut is made by an ordered, sequential cleavage of the two strands. The
      transferred strand is cut first, and then the nontransferred strand is cleaved.
      The single-strand nicked intermediate is seen to accumulate when Mn2+ is
      substituted for Mg2+ in the reaction or when certain mutant transposases are
      used. The fact that the transferred strand is cleaved before the non-transferred
      strand implies that the order of strand cleavages is not the determining factor
      that precludes a replicative mechanism of transposition.

PMID- 7644499
TI  - The product of the ataxia-telangiectasia group D complementing gene, ATDC,
      interacts with a protein kinase C substrate and inhibitor.
AB  - Ataxia-telangiectasia (AT) is an autosomal recessive human genetic disease
      characterized by immunological, neurological, and developmental defects and an
      increased risk of cancer. Cells from individuals with AT show sensitivity to
      ionizing radiation, elevated recombination, cell cycle abnormalities, and
      aberrant cytoskeletal organization. The molecular basis of the defect is unknown.
      A candidate AT gene (ATDC) was isolated on the basis of its ability to complement
      the ionizing radiation sensitivity of AT group D fibroblasts. Whether ATDC is
      mutated in any AT patients is not known. We have found that the ATDC protein
      physically interacts with the intermediate-filament protein vimentin, which is a
      protein kinase C substrate and colocalizing protein, and with an inhibitor of
      protein kinase C, hPKCI-1. Indirect immunofluorescence analysis of cultured cells
      transfected with a plasmid encoding an epitope-tagged ATDC protein localizes the
      protein to vimentin filaments. We suggest that the ATDC and hPKCI-1 proteins may
      be components of a signal transduction pathway that is induced by ionizing
      radiation and mediated by protein kinase C.

PMID- 7644498
TI  - The WW domain of Yes-associated protein binds a proline-rich ligand that differs
      from the consensus established for Src homology 3-binding modules.
AB  - The WW domain has previously been described as a motif of 38 semiconserved
      residues found in seemingly unrelated proteins, such as dystrophin, Yes
      associated protein (YAP), and two transcriptional regulators, Rsp-5 and FE65. The
      molecular function of the WW domain has been unknown until this time. Using a
      functional screen of a cDNA expression library, we have identified two putative
      ligands of the WW domain of YAP, which we named WBP-1 and WBP-2. Peptide sequence
      comparison between the two partial clones revealed a homologous region consisting
      of a proline-rich domain followed by a tyrosine residue (with the shared sequence
      PPPPY), which we shall call the PY motif. Binding assays and site-specific
      mutagenesis have shown that the PY motif binds with relatively high affinity and
      specificity to the WW domain of YAP, with the preliminary consensus XPPXY being
      critical for binding. Herein, we have implicated the WW domain with a role in
      mediating protein-protein interactions, as a variant of the paradigm set by Src
      homology 3 domains and their proline-rich ligands.

PMID- 7644500
TI  - The human papilloma virus 16E6 gene sensitizes human mammary epithelial cells to
      apoptosis induced by DNA damage.
AB  - Programmed cell death (apoptosis) is a normal physiological process, which could
      in principle be manipulated to play an important role in cancer therapy. The key
      importance of p53 expression in the apoptotic response to DNA-damaging agents has
      been stressed because mutant or deleted p53 is so common in most kinds of cancer.
      An important strategy, therefore, is to find ways to induce apoptosis in the
      absence of wild-type p53. In this paper, we compare apoptosis in normal human
      mammary epithelial cells, in cells immortalized with human papilloma virus (HPV),
      and in mammary carcinoma cell lines expressing wild-type p53, mutant p53, or no
      p53 protein. Apoptosis was induced with mitomycin C (MMC), a DNA cross-linking
      and damaging agent, or with staurosporine (SSP), a protein kinase inhibitor. The
      normal and HPV-transfected cells responded more strongly to SSP than did the
      tumor cells. After exposure to MMC, cells expressing wild-type p53 underwent
      extensive apoptosis, whereas cells carrying mutated p53 responded weakly. Primary
      breast cancer cell lines null for p53 protein were resistant to MMC. In contrast,
      two HPV immortalized cell lines in which p53 protein was destroyed by E6
      modulated ubiquitinylation were highly sensitive to apoptosis induced by MMC.
      Neither p53 mRNA nor protein was induced in the HPV immortalized cells after MMC
      treatment, although p53 protein was elevated by MMC in cells with wild-type p53.
      Importantly, MMC induced p21 mRNA but not p21 protein expression in the HPV
      immortalized cells. Thus, HPV 16E6 can sensitize mammary epithelial cells to MMC
      induced apoptosis via a p53- and p21-independent pathway. We propose that the HPV
      16E6 protein modulates ubiquitin-mediated degradation not only of p53 but also of
      p21 and perhaps other proteins involved in apoptosis.

PMID- 7644501
TI  - Multiple Bcl-2 family members demonstrate selective dimerizations with Bax.
AB  - A family of Bcl-2-related proteins regulates cell death and shares highly
      conserved BH1 and BH2 domains. BH1 and BH2 domains of Bcl-2 were required for it
      to heterodimerize with Bax and to repress apoptosis. A yeast two-hybrid assay
      accurately reproduced this interaction and defined a selectivity and hierarchy of
      further dimerizations. Bax also heterodimerizes with Bcl-xL, Mcl-1, and A1. A Gly
      159-->Ala substitution in BH1 of Bcl-xL disrupted its heterodimerization with Bax
      and abrogated its inhibition of apoptosis in mammalian cells. This suggests that
      the susceptibility to apoptosis is determined by multiple competing dimerizations
      in which Bax may be a common partner.

PMID- 7644502
TI  - The biosynthetic gene cluster for the polyketide immunosuppressant rapamycin.
AB  - The macrocyclic polyketides rapamycin and FK506 are potent immunosuppressants
      that prevent T-cell proliferation through specific binding to intracellular
      protein receptors (immunophilins). The cloning and specific alteration of the
      biosynthetic genes for these polyketides might allow the biosynthesis of
      clinically valuable analogues. We report here that three clustered polyketide
      synthase genes responsible for rapamycin biosynthesis in Streptomyces
      hygroscopicus together encode 14 homologous sets of enzyme activities (modules),
      each catalyzing a specific round of chain elongation. An adjacent gene encodes a
      pipecolate-incorporating enzyme, which completes the macrocycle. The total of 70
      constituent active sites makes this the most complex multienzyme system
      identified so far. The DNA region sequenced (107.3 kbp) contains 24 additional
      open reading frames, some of which code for proteins governing other key steps in
      rapamycin biosynthesis.

PMID- 7644503
TI  - Reexpression of retinoic acid receptor (RAR) gamma or overexpression of RAR alpha
      or RAR beta in RAR gamma-null F9 cells reveals a partial functional redundancy
      between the three RAR types.
AB  - Disruption of retinoic acid receptor (RAR) gamma in F9 embryonal carcinoma cells
      leads to aberrent differentiation and reduced activation of expression of several
      all-trans-retinoic acid (RA)-induced genes. We have analyzed the expression of
      several additional RA-responsive genes in RAR alpha- and RAR gamma-null F9 cells.
      The RA-induced activation of Cdx1, Gap43, Stra4, and Stra6 was specifically
      impaired in RAR gamma-null cells, supporting the idea that each RAR may regulate
      distinct subsets of target genes. To further investigate the role of RAR gamma in
      F9 cell differentiation, "rescue" cell lines reexpressing RAR gamma 2 or
      overexpressing either RAR alpha 1 or RAR beta 2 were established in RAR gamma
      null cells. Reexpression of RAR gamma or overexpression of RAR alpha restored
      both target-gene activation and the differentiation potential. In contrast, over
      expression of RAR beta only poorly restored differentiation, although it could
      replace RAR gamma for the activation of target genes. Functional redundancy
      between the various RARs is discussed.

PMID- 7644504
TI  - Expression of PTPH1, a rat protein tyrosine phosphatase, is restricted to the
      derivatives of a specific diencephalic segment.
AB  - Studies to date have identified only a few proteins that are expressed in a
      segment-specific manner within the mammalian brain. Here we report that a
      nonreceptor protein tyrosine phosphatase, PTPH1, is selectively expressed in the
      adult thalamus. Expression of PTPH1 mRNA is detected in most, but not all,
      thalamic nuclei. Nuclei that are derived embryonically from the dorsal thalamus
      and project to the neocortex express this gene, whereas those derived from the
      ventral thalamus do not. PTPH1 mRNA expression is also restricted to the dorsal
      thalamus during development and, thus, can serve as a specific marker for the
      dorsal thalamic nuclei. Since the subcellular localization of PTPH1 protein is
      not known, its functional role is not clear. However, the restriction of its
      expression to the thalamic nuclei that have thalamocortical connections suggests
      that PTPH1 may play a role in the maintenance of these connections or in
      determining the physiological properties of thalamic relay nuclei.

PMID- 7644505
TI  - Frequency encoding in excitable systems with applications to calcium
      oscillations.
AB  - A number of excitable cell types respond to a constant hormonal stimulus with a
      periodic oscillation in intracellular calcium. The frequency of oscillation is
      often proportional to the hormonal stimulus, and one says that the stimulus is
      frequency encoded. Here we develop a theory of frequency encoding in excitable
      systems and apply it to intracellular calcium oscillations that results from
      increases in the intracellular level of inositol 1,4,5-triphosphate.

PMID- 7644506
TI  - Geographic and climatic control of primate diversity.
AB  - Although the comparative ecology of primates has been relatively well studied and
      there have been a number of outstanding studies of individual primate
      communities, the factors determining primate species diversity on either a local
      or regional level are largely unexplored. Understanding the determinants of
      species abundance is an important aspect of biodiversity and is critical for
      interpreting the comparative ecology of these different communities and for
      designing effective strategies of conservation. Comparative analysis of species
      diversity in more than 70 primate communities from South America, Africa,
      Madagascar, and Asia shows that on major continental areas and large tropical
      islands, there is a high positive correlation between the number of primate
      species and the area of tropical forest. Within major continental areas, the
      species diversity at individual sites is highly correlated with mean annual
      rainfall for South America, Africa, and Madagascar, but not Asia.

PMID- 7644507
TI  - Identification of receptor ligands and receptor subtypes using antagonists in a
      capillary electrophoresis single-cell biosensor separation system.
AB  - A capillary electrophoresis system with single-cell biosensors as a detector has
      been used to separate and identify ligands in complex biological samples. The
      power of this procedure was significantly increased by introducing antagonists
      that inhibited the cellular response from selected ligand-receptor interactions.
      The single-cell biosensor was based on the ligand-receptor binding and G-protein
      mediated signal transduction pathways in PC12 and NG108-15 cell lines. Receptor
      activation was measured as increases in cytosolic free calcium ion concentration
      by using fluorescence microscopy with the intracellular calcium ion indicator
      fluo-3-acetoxymethyl ester. Specifically, a mixture of bradykinin (BK) and
      acetylcholine (ACh) was fractionated and the components were identified by
      inhibiting the cellular response with icatibant (HOE 140), a selective antagonist
      to the BK B2 receptor subtype (B2BK), and atropine, an antagonist to muscarinic
      ACh receptor subtypes. Structurally related forms of BK were also identified
      based on inhibiting B2BK receptors. Applications of this technique include
      identification of endogenous BK in a lysate of human hepatocellular carcinoma
      cells (Hep G2) and screening for bioactivity of BK degradation products in human
      blood plasma. The data demonstrate that the use of antagonists with a single-cell
      biosensor separation system aids identification of separated components and
      receptor subtypes.

PMID- 7644508
TI  - Interaction of herpes simplex virus 1 origin-binding protein with DNA polymerase
      alpha.
AB  - The herpes simplex virus 1 (HSV-1) genome encodes seven polypeptides that are
      required for its replication. These include a heterodimeric DNA polymerase, a
      single-strand-DNA-binding protein, a heterotrimeric helicase/primase, and a
      protein (UL9 protein) that binds specifically to an HSV-1 origin of replication
      (oris). We demonstrate here that UL9 protein interacts specifically with the 180
      kDa catalytic subunit of the cellular DNA polymerase alpha-primase. This
      interaction can be detected by immunoprecipitation with antibodies directed
      against either of these proteins, by gel mobility shift of an oris-UL9 protein
      complex, and by stimulation of DNA polymerase activity by the UL9 protein. These
      findings suggest that enzymes required for cellular DNA replication also
      participate in HSV-1 DNA replication.

PMID- 7644509
TI  - A molecular anchor for stabilizing triple-helical DNA.
AB  - Molecular modeling has been used to predict that 2,6-disubstituted
      amidoanthraquinones, and not the 1,4 series, should preferentially interact with
      and stabilize triple-stranded DNA structures over duplex DNA. This is due to
      marked differences in the nature of chromophore-base stacking and groove
      accessibility for the two series. A DNA foot-printing method that monitors the
      extent of protection from DNase I cleavage on triplex formation has been used to
      examine the effects of a number of synthetic isomer compounds in the 1,4 and 2,6
      series. The experimental results are in accord with the predicted behavior and
      confirm that the 1,4 series bind preferentially to double- rather than triple
      stranded DNA, whereas the isomeric 2,6 derivatives markedly favor binding to
      triplex DNA.

PMID- 7644511
TI  - Oxytocin mediates atrial natriuretic peptide release and natriuresis after volume
      expansion in the rat.
AB  - Our previous studies have shown that stimulation of the anterior ventral third
      ventricular region increases atrial natriuretic peptide (ANP) release, whereas
      lesions of this structure, the median eminence, or removal of the neural lobe of
      the pituitary block ANP release induced by blood volume expansion (BVE). These
      results indicate that participation of the central nervous system is crucial in
      these responses, possibly through mediation by neurohypophysial hormones. In the
      present research we investigated the possible role of oxytocin, one of the two
      principal neurohypophysial hormones, in the mediation of ANP release. Oxytocin (1
      10 nmol) injected i.p. caused significant, dose-dependent increases in urinary
      osmolality, natriuresis, and kaliuresis. A delayed antidiuretic effect was also
      observed. Plasma ANP concentrations increased nearly 4-fold (P < 0.01) 20 min
      after i.p. oxytocin (10 nmol), but there was no change in plasma ANP values in
      control rats. When oxytocin (1 or 10 nmol) was injected i.v., it also induced a
      dose-related increase in plasma ANP at 5 min (P < 0.001). BVE by intra-atrial
      injection of isotonic saline induced a rapid (5 min postinjection) increase in
      plasma oxytocin and ANP concentrations and a concomitant decrease in plasma
      arginine vasopressin concentration. Results were similar with hypertonic volume
      expansion, except that this induced a transient (5 min) increase in plasma
      arginine vasopressin. The findings are consistent with the hypothesis that
      baroreceptor activation of the central nervous system by BVE stimulates the
      release of oxytocin from the neurohypophysis. This oxytocin then circulates to
      the right atrium to induce release of ANP, which circulates to the kidney and
      induces natriuresis and diuresis, which restore body fluid volume to normal
      levels.

PMID- 7644510
TI  - 14-3-3 proteins associate with cdc25 phosphatases.
AB  - The cdc25 phosphatases play key roles in cell cycle progression by activating
      cyclin-dependent kinases. Two members of the 14-3-3 protein family have been
      isolated in a yeast two-hybrid screen designed to identify proteins that interact
      with the human cdc25A and cdc25B phosphatases. Genes encoding the human homolog
      of the 14-3-3 epsilon protein and the previously described 14-3-3 beta protein
      have been isolated in this screening. 14-3-3 proteins constitute a family of well
      conserved eukaryotic proteins that were originally isolated in mammalian brain
      preparations and that possess diverse biochemical activities related to signal
      transduction. We present evidence that indicates that cdc25 and 14-3-3 proteins
      physically interact both in vitro and in vivo. 14-3-3 protein does not, however,
      affect the phosphatase activity of cdc25A. Raf-1, which is known to bind 14-3-3
      proteins, has recently been shown to associate with cdc25A and to stimulate its
      phosphatase activity. 14-3-3 protein, however, has no effect on the cdc25A-kinase
      activity of Raf-1. Instead, 14-3-3 may facilitate the association of cdc25 with
      Raf-1 in vivo, participating in the linkage between mitogenic signaling and the
      cell cycle machinery.

PMID- 7644512
TI  - Depletion-activated calcium current is inhibited by protein kinase in RBL-2H3
      cells.
AB  - Whole-cell patch-clamp recordings and single-cell Ca2+ measurements were used to
      study the control of Ca2+ entry through the Ca2+ release-activated Ca2+ influx
      pathway (ICRAC) in rat basophilic leukemia cells. When intracellular inositol
      1,4,5-trisphosphate (InsP3)-sensitive stores were depleted by dialyzing cells
      with high concentrations of InsP3, ICRAC inactivated only slightly in the absence
      of ATP. Inclusion of ATP accelerated inactivation 2-fold. The inactivation was
      increased further by the ATP analogue adenosine 5'-[gamma-thio]triphosphate,
      which is readily used by protein kinases, but not by 5'-adenylyl
      imidodiphosphate, another ATP analogue that is not used by kinases. Neither
      cyclic nucleotides nor inhibition of calmodulin or tyrosine kinase prevented the
      inactivation. Staurosporine and bisindolylmaleimide, protein kinase C inhibitors,
      reduced inactivation of ICRAC, whereas phorbol ester accelerated inactivation of
      the current. These results demonstrate that a protein kinase-mediated
      phosphorylation, probably through protein kinase C, inactivates ICRAC. Activation
      of the adenosine receptor (A3 type) in RBL cells did not evoke much Ca2+ influx
      or systematic activation of ICRAC. After protein kinase C was blocked, however,
      large ICRAC was observed in all cells and this was accompanied by large Ca2+
      influx. The ability of a receptor to evoke Ca2+ entry is determined, at least in
      part, by protein kinase C. Antigen stimulation, which triggers secretion through
      a process that requires Ca2+ influx, activated ICRAC. The regulation of ICRAC by
      protein kinase will therefore have important consequences on cell functioning.

PMID- 7644513
TI  - An automated multiplex oligonucleotide synthesizer: development of high
      throughput, low-cost DNA synthesis.
AB  - An automated oligonucleotide synthesizer has been developed that can
      simultaneously and rapidly synthesize up to 96 different oligonucleotides in a 96
      well microtiter format using phosphoramidite synthesis chemistry. A modified 96
      well plate is positioned under reagent valve banks, and appropriate reagents are
      delivered into individual wells containing the growing oligonucleotide chain,
      which is bound to a solid support. Each well has a filter bottom that enables the
      removal of spent reagents while retaining the solid support matrix. A seal design
      is employed to control synthesis environment and the entire instrument is
      automated via computer control. Synthesis cycle times for 96 couplings are < 11
      min, allowing a plate of 96 20-mers to be synthesized in < 5 hr. Oligonucleotide
      synthesis quality is comparable to commercial machines, with average coupling
      efficiencies routinely > 98% across the entire 96-well plate. No significant well
      to-well variations in synthesis quality have been observed in > 6000
      oligonucleotides synthesized to date. The reduced reagent usage and increased
      capacity allow the overall synthesis cost to drop by at least a factor of 10.
      With the development of this instrument, it is now practical and cost-effective
      to synthesize thousands to tens of thousands of oligonucleotides.

PMID- 7644514
TI  - Structural organization of mouse peroxisome proliferator-activated receptor gamma
      (mPPAR gamma) gene: alternative promoter use and different splicing yield two
      mPPAR gamma isoforms.
AB  - To gain insight into the regulation of expression of peroxisome proliferator
      activated receptor (PPAR) isoforms, we have determined the structural
      organization of the mouse PPAR gamma (mPPAR gamma) gene. This gene extends > 105
      kb and gives rise to two mRNAs (mPPAR gamma 1 and mPPAR gamma 2) that differ at
      their 5' ends. The mPPAR gamma 2 cDNA encodes an additional 30 amino acids N
      terminal to the first ATG codon of mPPAR gamma 1 and reveals a different 5'
      untranslated sequence. We show that mPPAR gamma 1 mRNA is encoded by eight exons,
      whereas the mPPAR gamma 2 mRNA is encoded by seven exons. Most of the 5'
      untranslated sequence of mPPAR gamma 1 mRNA is encoded by two exons, whereas the
      5' untranslated sequence and the extra 30 N-terminal amino acids of mPPAR gamma 2
      are encoded by one exon, which is located between the second and third exons
      coding for mPPAR gamma 1. The last six exons of mPPAR gamma gene code for
      identical sequences in mPPAR gamma 1 and mPPAR gamma 2 isoforms. The mPPAR gamma
      1 and mPPAR gamma 2 isoforms are transcribed from different promoters. The mPPAR
      gamma gene has been mapped to chromosome 6 E3-F1 by in situ hybridization using a
      biotin-labeled probe. These results establish that at least one of the PPAR genes
      yields more than one protein product, similar to that encountered with retinoid X
      receptor and retinoic acid receptor genes. The existence of multiple PPAR
      isoforms transcribed from different promoters could increase the diversity of
      ligand and tissue-specific transcriptional responses.

PMID- 7644516
TI  - Membrane disposition of the M5-M6 hairpin of Na+,K(+)-ATPase alpha subunit is
      ligand dependent.
AB  - Extensive proteolytic digestion of Na+,K(+)-ATPase (EC 3.6.1.37) by trypsin
      produces a preparation where most of the extramembrane portions of the alpha
      subunit have been digested away and the beta subunit remains essentially intact.
      The fragment Gln-737-Arg-829 of the Na+,K(+)-ATPase alpha subunit, which includes
      the putative transmembrane hairpin M5-M6, is readily, selectively, and
      irreversibly released from the posttryptic membrane preparation after incubation
      at 37 degrees C for several minutes. Once released from the membrane, the
      fragment aggregates but remains water soluble. Occlusion of K+ or Rb+
      specifically prevents release of the Gln-737-Arg-829 fragment into the
      supernatant. Labeling of the posttryptic membrane preparation with cysteine
      directed reagents revealed that Cys-802 (which is thought to be located within
      the M6 segment) is protected against the modification by Rb+ while this fragment
      is in the membrane but can be readily modified upon release. Cation occlusion
      apparently alters the folding and/or disposition of the M5-M6 fragment in the
      membrane in a way that does not occur when the fragment migrates to the aqueous
      phase. The ligand-dependent disposition of the M5-M6 hairpin in the membrane
      along with recent labeling studies suggest a key role for this segment in cation
      pumping by Na+,K(+)-ATPase.

PMID- 7644515
TI  - Cell-free activation of neutrophil NADPH oxidase by a phosphatidic acid-regulated
      protein kinase.
AB  - The phosphorylation-dependent mechanisms regulating activation of the human
      neutrophil respiratory-burst enzyme, NADPH oxidase, have not been elucidated. We
      have shown that phosphatidic acid (PA) and diacylglycerol (DG), products of
      phospholipase activation, synergize to activate NADPH oxidase in a cell-free
      system. We now report that activation by PA plus DG involves protein kinase
      activity, unlike other cell-free system activators. NADPH oxidase activation by
      PA plus DG is reduced approximately 70% by several protein kinase inhibitors [1
      (5-isoquinolinesulfonyl)piperazine, staurosporine, GF-109203X]. Similarly,
      depletion of ATP by dialysis reduces PA plus DG-mediated NADPH oxidase activation
      by approximately 70%. Addition of ATP, but not a nonhydrolyzable ATP analog, to
      the dialyzed system restores activation levels to normal. In contrast, these
      treatments have little effect on NADPH oxidase activation by arachidonic acid or
      SDS plus DG. PA plus DG induces the phosphorylation of a number of endogenous
      proteins. Phosphorylation is largely mediated by PA, not DG. A predominant
      substrate is p47-phox, a phosphoprotein component of NADPH oxidase.
      Phosphorylation of p47-phox precedes activation of NADPH oxidase and is markedly
      reduced by the protein kinase inhibitors. In contrast, arachidonic acid alone or
      SDS plus DG is a poor activator of protein phosphorylation in the cell-free
      system. Thus, PA induces activation of one or more protein kinases that regulate
      NADPH oxidase activation in a cell-free system. This cell-free system will be
      useful for identifying a functionally important PA-activated protein kinase(s)
      and for dissecting the phosphorylation-dependent mechanisms responsible for NADPH
      oxidase activation.

PMID- 7644517
TI  - The algT (algU) gene of Pseudomonas aeruginosa, a key regulator involved in
      alginate biosynthesis, encodes an alternative sigma factor (sigma E).
AB  - Chronic infection by alginate-producing (mucoid) Pseudomonas aeruginosa is the
      leading cause of mortality among cystic fibrosis (CF) patients. During the course
      of sustained infection, the production of an alginate capsule protects the
      bacteria and allows them to persist in the CF lung. One of the key regulators of
      alginate synthesis is the algT (algU) gene encoding a putative alternative sigma
      factor (sigma E). AlgT was hyperproduced and purified from Escherichia coli. The
      N-terminal sequence of the purified protein matched perfectly with that predicted
      from the DNA sequence. The purified protein, in the presence of E. coli RNA
      polymerase core enzyme, was able to initiate transcription of an algT promoter.
      Deletion of the -35 region of this promoter abolished this activity in vitro as
      well as in vivo. These data indicate that the algT gene encodes a sigma factor
      that is autoregulatory.

PMID- 7644518
TI  - Features of MotA proton channel structure revealed by tryptophan-scanning
      mutagenesis.
AB  - The MotA protein of Escherichia coli is a component of the flagellar motors that
      functions in transmembrane proton conduction. Here, we report several features of
      MotA structure revealed by use of a mutagenesis-based approach. Single tryptophan
      residues were introduced at many positions within the four hydrophobic segments
      of MotA, and the effects on function were measured. Function was disrupted
      according to a periodic pattern that implies that the membrane-spanning segments
      are alpha-helices and that identifies the lipid-facing parts of each helix. The
      results support a hypothesis for MotA structure and mechanism in which water
      molecules form most of the proton-conducting pathway. The success of this
      approach in studying MotA suggests that it could be useful in structure-function
      studies of other integral membrane proteins.

PMID- 7644519
TI  - Proofreading-defective DNA polymerase II increases adaptive mutation in
      Escherichia coli.
AB  - The role of Escherichia coli DNA polymerase (Pol) II in producing or avoiding
      mutations was investigated by replacing the chromosomal Pol II gene (polB+) by a
      gene encoding an exonuclease-deficient mutant Pol II (polBex1). The polBex1
      allele increased adaptive mutations on an episome in nondividing cells under
      lactose selection. The presence of a Pol III antimutator allele (dnaE915) reduced
      adaptive mutations in both polB+ cells and cells deleted for polB (polB delta 1)
      to below the wild-type level, suggesting that both Pol II and Pol III are
      synthesizing episomal DNA in nondividing cells but that in wild-type cells Pol
      III generates the adaptive mutations. The adaptive mutations were mainly -1 frame
      shifts occurring in short homopolymeric runs and were similar in wild-type, polB
      delta 1, and polBex1 strains. Mutations produced by both Pol III and Pol II ex1
      were corrected by the mutHLS mismatch repair system.

PMID- 7644520
TI  - Identification, purification, and characterization of a zyxin-related protein
      that binds the focal adhesion and microfilament protein VASP (vasodilator
      stimulated phosphoprotein).
AB  - VASP (vasodilator-stimulated phosphoprotein), an established substrate of cAMP-
      and cGMP-dependent protein kinases in vitro and in living cells, is associated
      with focal adhesions, microfilaments, and membrane regions of high dynamic
      activity. Here, the identification of an 83-kDa protein (p83) that specifically
      binds VASP in blot overlays of different cell homogenates is reported. With VASP
      overlays as a detection tool, p83 was purified from porcine platelets and used to
      generate monospecific polyclonal antibodies. VASP binding to purified p83 in
      solid-phase binding assays and the closely matching subcellular localization in
      double-label immunofluorescence analyses demonstrated that both proteins also
      directly interact as native proteins in vitro and possibly in living cells. The
      subcellular distribution, the biochemical properties, as well as microsequencing
      data revealed that porcine platelet p83 is related to chicken gizzard zyxin and
      most likely represents the mammalian equivalent of the chicken protein. The VASP
      p83 interaction may contribute to the targeting of VASP to focal adhesions,
      microfilaments, and dynamic membrane regions. Together with our recent
      identification of VASP as a natural ligand of the profilin poly-(L-proline)
      binding site, our present results suggest that, by linking profilin to zyxin/p83,
      VASP may participate in spatially confined profilin-regulated F-actin formation.

PMID- 7644521
TI  - Nonsteroidal antiinflammatory drugs cause apoptosis and induce cyclooxygenases in
      chicken embryo fibroblasts.
AB  - Programmed cell death (apoptosis) is an intrinsic part of organismal development
      and aging. Here we report that many nonsteroidal antiinflammatory drugs (NSAIDs)
      cause apoptosis when applied to v-src-transformed chicken embryo fibroblasts
      (CEFs). Cell death was characterized by morphological changes, the induction of
      tissue transglutaminase, and autodigestion of DNA. Dexamethasone, a repressor of
      cyclooxygenase (COX) 2, neither induced apoptosis nor altered the NSAID effect.
      Prostaglandin E2, the primary eicosanoid made by CEFs, also failed to inhibit
      apoptosis. Expression of the protooncogene bcl-2 is very low in CEFs and is not
      altered by NSAID treatment. In contrast, p20, a protein that may protect against
      apoptosis when fibroblasts enter G0 phase, was strongly repressed. The NSAID
      concentrations used here transiently inhibit COXs. Nevertheless, COX-1 and COX-2
      mRNAs and COX-2 protein were induced. In some cell types, then, chronic NSAID
      treatment may lead to increased, rather than decreased, COX activity and, thus,
      exacerbate prostaglandin-mediated inflammatory effects. The COX-2 transcript is a
      partially spliced and nonfunctional form previously described. Thus, these
      findings suggest that COXs and their products play key roles in preventing
      apoptosis in CEFs and perhaps other cell types.

PMID- 7644523
TI  - A mutated intron sequence codes for an antigenic peptide recognized by cytolytic
      T lymphocytes on a human melanoma.
AB  - We have identified an antigen recognized on a human melanoma by autologous
      cytolytic T lymphocytes. It is encoded by a gene that is expressed in many normal
      tissues. Remarkably, the sequence coding for the antigenic peptide is located
      across an exon-intron junction. A point mutation is present in the intron that
      generates an amino acid change that is essential for the recognition of the
      peptide by the anti-tumor cytotoxic T lymphocytes. This observation suggests that
      the T-cell-mediated surveillance of the integrity of the genome may extend to
      some intronic regions.

PMID- 7644524
TI  - Characterization of a Leishmania tropica antigen that detects immune responses in
      Desert Storm viscerotropic leishmaniasis patients.
AB  - A chronic debilitating parasitic infection, viscerotropic leishmaniasis (VTL),
      has been described in Operation Desert Storm veterans. Diagnosis of this disease,
      caused by Leishmania tropica, has been difficult due to low or absent specific
      immune responses in traditional assays. We report the cloning and
      characterization of two genomic fragments encoding portions of a single 210-kDa
      L. tropica protein useful for the diagnosis of VTL in U.S. military personnel.
      The recombinant proteins encoded by these fragments, recombinant (r) Lt-1 and rLt
      2, contain a 33-amino acid repeat that reacts with sera from Desert Storm VTL
      patients and with sera from L. tropica-infected patients with cutaneous
      leishmaniasis. Antibody reactivities to rLt-1 indicated a bias toward IgG2 in VTL
      patient sera. Peripheral blood mononuclear cells from VTL patients produced
      interferon gamma, but not interleukin 4 or 10, in response to rLt-1. No cytokine
      production was observed in response to parasite lysate. The results indicate that
      specific leishmanial antigens may be used to detect immune responses in VTL
      patients with chronic infections.

PMID- 7644522
TI  - Drosophila hormone receptor 38: a second partner for Drosophila USP suggests an
      unexpected role for nuclear receptors of the nerve growth factor-induced protein
      B type.
AB  - In Drosophila the response to the hormone ecdysone is mediated in part by
      Ultraspiracle (USP) and ecdysone receptor (EcR), which are members of the nuclear
      receptor superfamily. Heterodimers of these proteins bind to ecdysone response
      elements (EcREs) and ecdysone to modulate transcription. Herein we describe
      Drosophila hormone receptor 38 (DHR38) and Bombyx hormone receptor 38 (BHR38),
      two insect homologues of rat nerve growth factor-induced protein B (NGFI-B).
      Although members of the NGFI-B family are thought to function exclusively as
      monomers, we show that DHR38 and BHR38 in fact interact strongly with USP and
      that this interaction is evolutionarily conserved. DHR38 can compete in vitro
      against EcR for dimerization with USP and consequently disrupt EcR-USP binding to
      an EcRE. Moreover, transfection experiments in Schneider cells show that DHR38
      can affect ecdysone-dependent transcription. This suggests that DHR38 plays a
      role in the ecdysone response and that more generally NGFI-B type receptors may
      be able to function as heterodimers with retinoid X receptor type receptors in
      regulating transcription.

PMID- 7644525
TI  - Role of pili and the phase-variable PilC protein in natural competence for
      transformation of Neisseria gonorrhoeae.
AB  - The Gram-negative bacterial pathogen Neisseria gonorrhoeae is naturally competent
      for transformation with species-related DNA. We show here that two phase-variable
      pilus-associated proteins, the major pilus subunit (pilin, or PilE) and PilC, a
      factor known to function in the assembly and adherence of gonococcal pili, are
      essential for transformation competence. The PilE and PilC proteins are necessary
      for the conversion of linearized plasmid DNA carrying the Neisseria-specific DNA
      uptake signal into a DNase-resistant form. The biogenesis of typical pilus fibers
      is neither essential nor sufficient for this process. DNA uptake deficiency of
      defined piliated pilC1,2 double mutants can be complemented by expression of a
      cloned pilC2 gene in trans. The PilC defect can also be restored by the addition
      of purified PilC protein, or better, pili containing PilC protein, to the mutant
      gonococci. Our data suggest that the two phase-variable Pil proteins act on the
      bacterial cell surface and cooperate in DNA recognition and/or outer membrane
      translocation.

PMID- 7644526
TI  - Protein secretion by enteropathogenic Escherichia coli is essential for
      transducing signals to epithelial cells.
AB  - Enteropathogenic Escherichia coli (EPEC), a major cause of pediatric diarrhea,
      adheres to epithelial cells and activates host cell signal transduction pathways.
      We have identified five proteins that are secreted by EPEC and show that this
      secretion process is critical for triggering signal transduction events in
      epithelial cells. Protein secretion occurs via two pathways: one secretes a 110
      kDa protein and the other mediates export of the four remaining proteins.
      Secretion of all five proteins was regulated by temperature and the perA locus,
      two factors which regulate expression of other known EPEC virulence factors.
      Amino-terminal sequence analysis of the secreted polypeptides identified one
      protein (37 kDa) as the product of the eaeB gene, a genetic locus previously
      shown to be necessary for signal transduction. A second protein (39 kDa) showed
      significant homology with glyceraldehyde-3-phosphate dehydrogenase, while the
      other three proteins (110, 40, and 25 kDa) were unique. The secreted proteins
      associated with epithelial cells, and EaeB became resistant to protease digestion
      upon association, suggesting that intimate interactions are required for
      transducing signals.

PMID- 7644527
TI  - Enteropathogenic Escherichia coli contains a putative type III secretion system
      necessary for the export of proteins involved in attaching and effacing lesion
      formation.
AB  - Enteropathogenic Escherichia coli (EPEC) causes a characteristic histopathology
      in intestinal epithelial cells called the attaching and effacing lesion. Although
      the histopathological lesion is well described the bacterial factors responsible
      for it are poorly characterized. We have identified four EPEC chromosomal genes
      whose predicted protein sequences are similar to components of a recently
      described secretory pathway (type III) responsible for exporting proteins lacking
      a typical signal sequence. We have designated the genes sepA, sepB, sepC, and
      sepD (sep, for secretion of E. coli proteins). The predicted Sep polypeptides are
      similar to the Lcr (low calcium response) and Ysc (yersinia secretion) proteins
      of Yersinia species and the Mxi (membrane expression of invasion plasmid
      antigens) and Spa (surface presentation of antigens) regions of Shigella
      flexneri. Culture supernatants of EPEC strain E2348/69 contain several
      polypeptides ranging in size from 110 kDa to 19 kDa. Proteins of comparable size
      were recognized by human convalescent serum from a volunteer experimentally
      infected with strain E2348/69. A sepB mutant of EPEC secreted only the 110-kDa
      polypeptide and was defective in the formation of attaching and effacing lesions
      and protein-tyrosine phosphorylation in tissue culture cells. These phenotypes
      were restored upon complementation with a plasmid carrying an intact sepB gene.
      These data suggest that the EPEC Sep proteins are components of a type III
      secretory apparatus necessary for the export of virulence determinants.

PMID- 7644528
TI  - Molecular cloning and functional characterization of the Xenopus Ca(2+)-binding
      protein frequenin.
AB  - Frequenin was originally identified in Drosophila melanogaster as a Ca(2+)
      binding protein facilitating transmitter release at the neuromuscular junction.
      We have cloned the Xenopus frequenin (Xfreq) by PCR using degenerate primers
      combined with low-stringency hybridization. The deduced protein has 70% identity
      with Drosophila frequenin and about 38-58% identity with other Ca(2+)-binding
      proteins. The most prominent features are the four EF-hands, Ca(2+)-binding
      motifs. Xfreq mRNA is abundant in the brain and virtually nondetectable from
      adult muscle. Western blot analysis indicated that Xfreq is highly concentrated
      in the adult brain and is absent from nonneural tissues such as heart and kidney.
      During development, the expression of the protein correlated well with the
      maturation of neuromuscular synapses. To determine the function of Xfreq at the
      developing neuromuscular junction, the recombinant protein was introduced into
      Xenopus embryonic spinal neurons by early blastomere injection. Synapses made by
      spinal neurons containing exogenous Xfreq exhibited a much higher synaptic
      efficacy. These results provide direct evidence that frequenin enhances
      transmitter release at the vertebrate neuromuscular synapse and suggest its
      potential role in synaptic development and plasticity.

PMID- 7644529
TI  - Tonic stimulation of renin gene expression by nitric oxide is counteracted by
      tonic inhibition through angiotensin II.
AB  - This study was designed to examine the possible involvement of prostaglandins and
      nitric oxide (NO) in the renin stimulatory effect of angiotensin II (AngII)
      antagonists. To this end, plasma renin activities (PRAs) and renal renin mRNA
      levels were assayed in rats that were treated with the Ang-converting enzyme
      inhibitor ramipril or with the AngII AT1-receptor antagonist losartan. Ramipril
      and losartan increased PRA values from 7.5 +/- 1.6 to 86 +/- 6 and 78 +/- 22 ng
      of AngI per h per ml and renin mRNA levels from 112 +/- 9% to 391 +/- 20% and 317
      +/- 10%, respectively. Inhibition of prostaglandin formation with indomethacin
      did not influence basal or ramipril-affected PRA. Basal renin mRNA levels also
      were unchanged by indomethacin, while increases in renin mRNA levels after
      ramipril treatment were slightly reduced by indomethacin. Inhibition of NO
      synthase by nitro-L-arginine methyl ester (L-NAME) reduced PRA values to 3.2 +/-
      0.9, 34 +/- 13, and 12.1 +/- 2.7 ng of AngI per h per ml in control, ramipril
      treated, and losartan-treated animals, respectively. Renin mRNA levels were
      reduced to 77 +/- 14% under basal conditions and ramipril- and losartan-induced
      increases in renin mRNA levels were completely blunted after addition of L-NAME.
      The AngII antagonists, furthermore, induced an upstream recruitment of renin
      expressing cells in the renal afferent arterioles, which was also blunted by L
      NAME. These findings suggest that renin mRNA levels are tonically increased by NO
      and that the action of NO is counteracted by AngII.

PMID- 7644531
TI  - Molecular design of the N-methyl-D-aspartate receptor binding site for
      phencyclidine and dizolcipine.
AB  - The N-methyl-D-aspartate receptor (NMDAR), a pivotal entity for synaptic
      plasticity and excitotoxicity in the brain, is a target of psychotomimetic drugs
      such as phencyclidine (PCP) and dizolcipine (MK-801). In contrast, a related
      glutamate receptor, the alpha-amino-3-hydroxy-5-methyl-4-isoxazole
      propionate/kainate receptor GluR1, is weakly sensitive to these drugs. Three
      point mutations on GluR1, mimicking homologous residues on the NMDAR, confer the
      PCP and MK-801 blockade properties that are characteristic of the NMDAR--namely,
      high potency, voltage dependence, and use dependence. The molecular determinants
      that specify the PCP block appear confined to the putative M2 transmembrane
      segment, whereas the sensitivity to MK-801 requires an interplay between residues
      from M2 and M3. Given the plausible involvement of the NMDAR in the etiology of
      several neurodegenerative diseases and in excitotoxic neuronal cell death,
      tailored glutamate receptors with specific properties may be models for designing
      and screening new drugs targeted to prevent glutamate-mediated neural damage.

PMID- 7644530
TI  - An integral membrane component of coatomer-coated transport vesicles defines a
      family of proteins involved in budding.
AB  - We have isolated a major integral membrane protein from Golgi-derived coatomer
      coated vesicles. This 24-kDa protein, p24, defines a family of integral membrane
      proteins with homologs present in yeast and humans. In addition to sequence
      similarity, all p24 family members contain a motif with the characteristic heptad
      repeats found in coiled coils. When the yeast p24 isoform, yp24A, is knocked out
      in a strain defective for vesicle fusion, a dramatic reduction in the
      accumulation of transport vesicles is observed. Together, these results indicate
      a role for this protein family in the budding of coatamer-coated and other
      species of coated vesicles.

PMID- 7644532
TI  - Rapid acquisition of dendritic spines by visual thalamic neurons after blockade
      of N-methyl-D-aspartate receptors.
AB  - N-Methyl-D-aspartate (NMDA) receptors play an important role in the development
      of retinal axon arbors in the mammalian lateral geniculate nucleus (LGN). We
      investigated whether blockade of NMDA receptors in vivo or in vitro affects the
      dendritic development of LGN neurons during the period that retinogeniculate
      axons segregate into on-center and off-center sublaminae. Osmotic minipumps
      containing either the NMDA receptor antagonist D-2-amino-5-phosphonovaleric acid
      (D-APV) or saline were implanted in ferret kits at postnatal day 14. After 1
      week, LGN neurons were intracellularly injected with Lucifer yellow. Infusion of
      D-APV in vivo led to an increase in the number of branch points and in the
      density of dendritic spines compared with age-matched normal or saline-treated
      animals. To examine the time course of spine formation, crystals of 1,1'
      dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate were placed in the
      LGN in brain slices from 14- to 18-day-old ferrets. Labeled LGN cell dendrites
      were imaged on-line in living slices by confocal microscopy, with slices
      maintained either in normal perfusion medium or with the addition of D-APV or
      NMDA to the medium. Addition of D-APV in vitro at doses specific for blocking
      NMDA receptors led to a > 6-fold net increase in spine density compared with
      control or NMDA-treated slices. Spines appeared within a few hours of NMDA
      receptor blockade, indicating a rapid local response by LGN cells in the absence
      of NMDA receptor activation. Thus, activity-dependent structural changes in
      postsynaptic cells act together with changes in presynaptic arbors to shape
      projection patterns and specific retinogeniculate connections.

PMID- 7644533
TI  - Cardioprotective effect of insulin-like growth factor I in myocardial ischemia
      followed by reperfusion.
AB  - In the present study, the cardioprotective effects of insulin-like growth factor
      I (IGF-I) were examined in a murine model of myocardial ischemia reperfusion
      (i.e., 20 min + 24 hr). IGF-I (1-10 micrograms per rat) administered 1 hr prior
      to ischemia significantly attenuated myocardial injury (i.e., creatine kinase
      loss) compared to vehicle (P < 0.001). In addition, cardiac myeloperoxidase
      activity, an index of neutrophil accumulation, in the ischemic area was
      significantly attenuated by IGF-I (P < 0.001). This protective effect of IGF-I
      was not observed with des-(1-3)-IGF-I. Immunohistochemical analysis of ischemic
      reperfused myocardial tissue demonstrated markedly increased DNA fragmentation
      due to programmed cell death (i.e., apoptosis) compared to nonischemic
      myocardium. Furthermore, IGF-I significantly attenuated the incidence of myocyte
      apoptosis after myocardial ischemia and reperfusion. Therefore, IGF-I appears to
      be an effective agent for preserving ischemic myocardium from reperfusion injury
      and protects via two different mechanisms--inhibition of polymorphonuclear
      leukocyte-induced cardiac necrosis and inhibition of reperfusion-induced
      apoptosis of cardiac myocytes.

PMID- 7644534
TI  - Mutation of the principal sigma factor causes loss of virulence in a strain of
      the Mycobacterium tuberculosis complex.
AB  - Tuberculosis continues to be responsible for the deaths of millions of people,
      yet the virulence factors of the causative pathogens remain unknown. Genetic
      complementation experiments with strains of the Mycobacterium tuberculosis
      complex have identified a gene from a virulent strain that restores virulence to
      an attenuated strain. The gene, designated rpoV, has a high degree of homology
      with principal transcription or sigma factors from other bacteria, particularly
      Mycobacterium smegmatis and Streptomyces griseus. The homologous rpoV gene of the
      attenuated strain has a point mutation causing an arginine-->histidine change in
      a domain known to interact with promoters. To our knowledge, association of loss
      of bacterial virulence with a mutation in the principal sigma factor has not been
      previously reported. The results indicate either that tuberculosis organisms have
      an alternative principal sigma factor that promotes virulence genes or, more
      probably, that this particular mutant principal sigma factor is unable to promote
      expression of one or more genes required for virulence. Study of genes and
      proteins differentially regulated by the mutant transcription factor should
      facilitate identification of further virulence factors.

PMID- 7644535
TI  - Adaptation of Spodoptera exigua larvae to plant proteinase inhibitors by
      induction of gut proteinase activity insensitive to inhibition.
AB  - Tobacco plants were transformed with a cDNA clone of chymotrypsin/trypsin
      specific potato proteinase inhibitor II (PI2) under the control of a constitutive
      promoter. Although considerable levels of transgene expression could be
      demonstrated, the growth of Spodoptera exigua larvae fed with detached leaves of
      PI2-expressing plants was not affected. Analysis of the composition of tryptic
      gut activity demonstrated that only 18% of the proteinase activity of insects
      reared on these transgenic plants was sensitive to inhibition by PI2, whereas 78%
      was sensitive in insects reared on control plants. Larvae had compensated for
      this loss of tryptic activity by a 2.5-fold induction of new activity that was
      insensitive to inhibition by PI2. PI2-insensitive proteolytic activity was also
      induced in response to endogenous proteinase inhibitors of tobacco; therefore,
      induction of such proteinase activity may represent the mechanism by which
      insects that feed on plants overcome plant proteinase inhibitor defense.

PMID- 7644536
TI  - Diverse transposable elements are mobilized in hybrid dysgenesis in Drosophila
      virilis.
AB  - We describe a system of hybrid dysgenesis in Drosophila virilis in which at least
      four unrelated transposable elements are all mobilized following a dysgenic
      cross. The data are largely consistent with the superposition of at least three
      different systems of hybrid dysgenesis, each repressing a different transposable
      element, which break down following the hybrid cross, possibly because they share
      a common pathway in the host. The data are also consistent with a mechanism in
      which mobilization of a single element triggers that of others, perhaps through
      chromosome breakage. The mobilization of multiple, unrelated elements in hybrid
      dysgenesis is reminiscent of McClintock's evidence [McClintock, B. (1955)
      Brookhaven Symp. Biol. 8, 58-74] for simultaneous mobilization of different
      transposable elements in maize.

PMID- 7644537
TI  - Gene therapy for long-term expression of erythropoietin in rats.
AB  - The injection of recombinant erythropoietin (Epo) is now widely used for long
      term treatment of anemia associated with chronic renal failure, cancer, and human
      immunodeficiency virus infections. The ability to deliver this hormone by gene
      therapy rather than by repeated injections could provide substantial clinical and
      economic benefits. As a preliminary approach, we investigated in rats the
      expression and biological effects of transplanting autologous vascular smooth
      muscle cells transduced with a retroviral vector encoding rat Epo cDNA. Vector
      derived Epo secretion caused increases in reticulocytes, with peak levels of 7.8
      9.6% around day 10 after implantation. The initial elevation in reticulocytes was
      followed by clinically significant increases in hematocrit and hemoglobin for up
      to 11 weeks. Ten control and treated animals showed mean hematocrits of 44.9 +/-
      0.4% and 58.7 +/- 3.1%, respectively (P < 0.001), and hemoglobin values of 15.6
      +/- 0.1 g/dl and 19.8 +/- 0.9 g/dl, respectively (P < 0.001). There were no
      significant differences between control and treated animals in the number of
      white blood cells and platelets. Kidney and to a lesser extent liver are specific
      organs that synthesize Epo in response to tissue oxygenation. In the treated
      animals, endogenous Epo mRNA was largely down regulated in kidney and absent from
      liver. These results indicate that vascular smooth muscle cells can be
      genetically modified to provide treatment of anemias due to Epo deficiency and
      suggest that this cell type may be targeted in the treatment of other diseases
      requiring systemic therapeutic protein delivery.

PMID- 7644538
TI  - Apoptosis induced by a human milk protein.
AB  - To the breast-fed infant, human milk is more than a source of nutrients; it
      furnishes a wide array of molecules that restrict microbes, such as antibodies,
      bactericidins, and inhibitors of bacterial adherence. However, it has rarely been
      considered that human milk may also contain substances bioactive toward host
      cells. While investigating the effect of human milk on bacterial adherence to a
      human lung cancer cell line, we were surprised to discover that the milk killed
      the cells. Analysis of this effect revealed that a component of milk in a
      particular physical state--multimeric alpha-lact-albumin--is a potent Ca(2+)
      elevating and apoptosis-inducing agent with broad, yet selective, cytotoxic
      activity. Multimeric alpha-lactalbumin killed all transformed, embryonic, and
      lymphoid cells tested but spared mature epithelial elements. These findings raise
      the possibility that milk contributes to mucosal immunity not only by furnishing
      antimicrobial molecules but also by policing the function of lymphocytes and
      epithelium. Finally, analysis of the mechanism by which multimeric alpha
      lactalbumin induces apoptosis in transformed epithelial cells could lead to the
      design of antitumor agents.

PMID- 7644539
TI  - The cis-acting phorbol ester "12-O-tetradecanoylphorbol 13-acetate"-responsive
      element is involved in shear stress-induced monocyte chemotactic protein 1 gene
      expression.
AB  - Vascular endothelial cells, serving as a barrier between vessel and blood, are
      exposed to shear stress in the body. Although endothelial responses to shear
      stress are important in physiological adaption to the hemodynamic environments,
      they can also contribute to pathological conditions--e.g., in atherosclerosis and
      reperfusion injury. We have previously shown that shear stress mediates a
      biphasic response of monocyte chemotactic protein 1 (MCP-1) gene expression in
      vascular endothelial cells and that the regulation is at the transcriptional
      level. These observations led us to functionally analyze the 550-bp promoter
      region of the MCP-1-encoding gene to define the cis element responding to shear
      stress. The shear stress/luciferase assay on the deletion constructs revealed
      that a 38-bp segment (-53 to -90 bp relative to the transcription initiation
      site) containing two divergent phorbol ester "12-O-tetradecanoylphorbol 13
      acetate" (TPA)-responsive elements (TRE) is critical for shear inducibility. Site
      specific mutations on these two sites further demonstrated that the proximal one
      (TGACTCC) but not the distal one (TCACTCA) was shear-responsive. Shear
      inducibility was lost after the mutation or deletion of the proximal site. This
      molecular mechanism of shear inducibility of the MCP-1 gene was functional in
      both the epithelial-like HeLa cells and bovine aortic endothelial cells (BAEC).
      In a construct with four copies of the TRE consensus sequences TGACTACA followed
      by the rat prolactin minimal promoter and luciferase gene, shear stress induced
      the reporter activities by 35-fold and 7-fold in HeLa cells and BAEC,
      respectively. The application of shear stress on BAEC also induced a rapid and
      transient phosphorylation of mitogen-activated protein kinases. Pretreatment of
      BAEC with TPA attenuated the shear-induced mitogen-activated protein kinase
      phosphorylation, suggesting that shear stress and TPA share a similar signal
      transduction pathway in activating cells. The present study provides a molecular
      basis for the transient induction of MCP-1 gene by shear stress.

PMID- 7644540
TI  - Brain-derived neurotrophic factor rapidly enhances synaptic transmission in
      hippocampal neurons via postsynaptic tyrosine kinase receptors.
AB  - Although neurotrophins are primarily associated with long-term effects on
      neuronal survival and differentiation, recent studies have shown that acute
      changes in synaptic transmission can also be produced. In the hippocampus, an
      area critically involved in learning and memory, we have found that brain-derived
      neurotrophic factor (BDNF) rapidly enhanced synaptic efficacy through a
      previously unreported mechanism--increased postsynaptic responsiveness via a
      phosphorylation-dependent pathway. Within minutes of BDNF application to cultured
      hippocampal neurons, spontaneous firing rate was dramatically increased, as were
      the frequency and amplitude of excitatory postsynaptic currents. The increased
      frequency of postsynaptic currents resulted from the change in presynaptic
      firing. However, the increased amplitude was postsynaptic in origin because it
      was selectively blocked by intracellular injection of the tyrosine kinase
      receptor (Ntrk2/TrkB) inhibitor K-252a and potentiated by injection of the
      phosphatase inhibitor okadaic acid. These results suggest a role for BDNF in the
      modulation of synaptic transmission in the hippocampus.

PMID- 7644543
TI  - Asymmetry and human facial attractiveness: symmetry may not always be beautiful.
AB  - It has been postulated that levels of fluctuating asymmetry in human faces may be
      negatively related to components of fitness such as parasite-resistance; hence
      potential mates with low levels of asymmetry may appear more attractive. However,
      previous investigations of the relationship between asymmetry and facial
      attractiveness have confounded manipulations of asymmetry with facial
      'averageness' and mean trait size. In this experiment we performed a manipulation
      that altered asymmetry within a face without altering the mean size of facial
      features. These faces were then rated on attractiveness. Contrary to what was
      predicted, faces that were made more symmetrical were perceived as being less
      attractive. These results do not support the hypothesis that attractiveness is
      related to low levels of fluctuating asymmetry. The observed positive
      relationship between asymmetry and facial attractiveness may be because certain
      facial features (including those contributing to attractiveness) in fact show
      directional asymmetry or antisymmetry. Our manipulations thus render naturally
      asymmetric features symmetrical. This may make symmetric faces less attractive
      because of the reduction of natural directional asymmetries, perhaps making the
      faces appear unemotional. The role of fluctuating asymmetries alone in
      assessments of facial beauty is still unknown, although this experiment suggests
      fluctuating asymmetry is relatively unimportant compared with directional
      asymmetry.

PMID- 7644541
TI  - Induction of antigen-specific cytolytic T cells in situ in human melanoma by
      immunization with synthetic peptide-pulsed autologous antigen presenting cells.
AB  - Human melanoma cells can process the MAGE-1 gene product and present the
      processed nonapeptide EADPTGHSY on their major histocompatibility complex class I
      molecules, HLA-A1, as a determinant for cytolytic T lymphocytes (CTLs).
      Considering that autologous antigen presenting cells (APCs) pulsed with the
      synthetic nonapeptide might, therefore, be immunogenic, melanoma patients whose
      tumor cells express the MAGE-1 gene and who are HLA-A1+ were immunized with a
      vaccine made of cultured autologous APCs pulsed with the synthetic nonapeptide.
      Analyses of the nature of the in vivo host immune response to the vaccine
      revealed that the peptide-pulsed APCs are capable of inducing autologous melanoma
      reactive and the nonapeptide-specific CTLs in situ at the immunization site and
      at distant metastatic disease sites.

PMID- 7644544
TI  - Parvocellular neurons limit motion acuity in human peripheral vision.
AB  - It is generally believed that the perception of moving targets is mediated by the
      magnocellular (M) pathway in primate vision, but evidence is emerging that the
      parvocellular (P) pathway may also play a role in motion perception. Human
      peripheral vision is susceptible to anomalous motion perception because of
      spatial aliasing, and in this study we used this fact to determine if the P
      pathway can mediate information about low- and high-velocity stimuli.
      Psychometric functions relating visual performance to stimulus spatial frequency
      were measured for the directional discrimination of drifting sinusoidal gratings
      presented at 40 degrees eccentricity. Applying the sampling theorem to our
      results, we estimated that the Nyquist frequency of the limiting sampling array
      for directional discrimination is 1.7 cycles per degree. This result was compared
      with the Nyquist limit and spatial filtering properties of M and P ganglion cells
      in the human peripheral retina, calculated from histological data on their
      density and dendritic field size. Our results provide evidence to suggest that
      the reversed motion illusion in human peripheral vision is due to spatial
      aliasing by the P ganglion cell mosaic. We conclude that the sampling density of
      P ganglion cells limits veridical motion acuity in human peripheral vision, even
      for high-velocity targets. This provides further evidence that the P pathway is
      involved in processing information about motion.

PMID- 7644545
TI  - Tissue distribution of the SALMFamide neuropeptides S1 and S2 in the starfish
      Asterias rubens using novel monoclonal and polyclonal antibodies. I. Nervous and
      locomotory systems.
AB  - The recent isolation and characterization of the SALMFamide neuropeptides (S1 and
      S2) from the starfish Asterias rubens has initiated a series of single- and
      double-labelling immunocytochemical studies to ascertain their tissue
      distribution and cellular localization. Specific novel monoclonal and polyclonal
      antisera have been raised against these neuropeptides and used in optical
      immunocytochemistry (ICC). The results of the present study reveal, for the first
      time, the widespread neuronal distribution of S2 localized to axons and perikarya
      of the radial nerve cord and tube foot ectoneural nerve plexus. Double labelling
      revealed a predominantly separate localization for S1 and S2 immunoreactivity.
      The potential functional roles of S1 and S2 in the radial nerve cord (RNC) and
      tube feet of Asterias rubens are discussed.

PMID- 7644542
TI  - Amyloid precursor protein processing is stimulated by metabotropic glutamate
      receptors.
AB  - Stimulation of muscarinic m1 or m3 receptors can, by generating diacylglycerol
      and activating protein kinase C, accelerate the breakdown of the amyloid
      precursor protein (APP) to form soluble, nonamyloidogenic derivatives (APPs), as
      previously shown. This relationship has been demonstrated in human glioma and
      neuroblastoma cells, as well as in transfected human embryonic kidney 293 cells
      and PC-12 cells. We now provide evidence that stimulation of metabotropic
      glutamate receptors (mGluRs), which also are coupled to phosphatidylinositol 4,5
      bisphosphate hydrolysis, similarly accelerates processing of APP into
      nonamyloidogenic APPs. This process is demonstrated both in hippocampal neurons
      derived from fetal rats and in human embryonic kidney 293 cells transfected with
      cDNA expression constructs encoding the mGluR 1 alpha subtype. In hippocampal
      neurons, both an mGluR antagonist, L-(+)-2-amino-3-phosphonopropionic acid, and
      an inhibitor of protein kinase C, GF 109203X, blocked the APPs release evoked by
      glutamate receptor stimulation. Ionotropic glutamate agonists, N-methyl-D
      aspartate or S(-)-5-fluorowillardiine, failed to affect APPs release. These data
      show that selective mGluR agonists that initiate signal-transduction events can
      regulate APP processing in bona fide primary neurons and transfected cells. As
      glutamatergic neurons in the cortex and hippocampus are damaged in Alzheimer
      disease, amyloid production in these regions may be enhanced by deficits in
      glutamatergic neurotransmission.

PMID- 7644546
TI  - Reproductive costs and litter size in the bank vole.
AB  - The potential reproductive costs for free-ranging bank vole (Clethrionomys
      glareolus) offspring and mothers were assessed by manipulating litter size and by
      determining the effects of nursing varied numbers of offspring. Litter
      enlargement did not increase the number of weanlings per mother. The mass of
      juveniles was significantly lower in the enlarged litters and higher in the
      reduced litters, compared to the control group. However, the survival of
      juveniles from weaning aged three months did not depend on their mass at weaning.
      Data from a previous study (Mappes et al. 1995) indicated that a higher mass at
      weaning may increase juveniles' abilities to maturate and breed during their
      summer of birth. Manipulation of litter size did not significantly affect the
      mass or survival of mothers or the success of subsequent breeding. The size of
      home ranges did correlate positively with the initial litter size. However, space
      use by females did not change with the degree of manipulation. Our results
      indicate that females nursing enlarged litters produce smaller offspring at
      weaning with no residual effects on future maternal survival or reproduction.
      Mothers did not seem to compensate the nursing costs with increased parental
      effort (which should be reflected in the condition of mothers or in the use of
      resources), for example, in an enlarged size of home range. Probably the
      possibility of obtaining a larger home range is constrained by the other breeding
      females, in a saturated breeding population. These results may support the
      optimal investment hypothesis that a female will produce a particular litter size
      which gives the best reproductive success in the particular environment where
      offspring are nursed.

PMID- 7644547
TI  - Discrimination by female mice between the odours of parasitized and non
      parasitized males.
AB  - The detection and avoidance of parasitized males has been proposed to be a
      component of female mate choice. We investigated whether or not female laboratory
      mice, Mus musculus domesticus, could discriminate between parasitized and non
      parasitized males on the basis of odour. Female mice were given a choice between
      the urine and other odorous secretions of either a male mouse sub-clinically
      infected for five days with the naturally occurring, enteric, single host,
      protozoan parasite, Eimeria vermiformis, or an uninfected male. Females showed a
      marked preference for the odours of non-parasitized male mice over those of the
      parasitized males; as measured by number of investigations, time spent per
      investigation, and total investigation time of the odours in a choice situation.
      Female mice also displayed an overwhelming initial, or first choice, preference
      for the odours of the non-parasitized male mice over those of the parasitized
      males. These observations show that female mice can distinguish between the
      odours of parasitized and non-parasitized males, and discriminate against
      parasitized males on the basis of odour. We suggest that the detection and
      avoidance of infected males by female mice through odour cues may function to
      reduce parasite transmission and potentially serve as a component of female mate
      selection or choice.

PMID- 7644548
TI  - Mortality factors in a cyclic vole population.
AB  - The causes of cyclic fluctuations in microtine rodent populations are still a
      bone of contention. In particular, the actual causes of mortality in the
      different phases of the 3-4-year vole are an enigma. We present results from
      studies of radio-collared voles (Microtus agrestis, M. rossiaemeridionalis and
      Clethrionomys glareolus), which show that small mustelid predation was the major
      mortality factor of voles in the decline phase, but had less importance in the
      increase phase of the 3-year population cycle. After the initial decline in the
      non-breeding season (winter), vole-kill rate from predators increased to a point
      where mortality substantially exceeded the reproductive capacity of microtine
      prey. Our results suggest that predators may alone cause a decline in the density
      of these vertebrate-prey populations.

PMID- 7644549
TI  - Evolution and phylogeny of Wolbachia: reproductive parasites of arthropods.
AB  - Wolbachia are cytoplasmically inherited bacteria found in reproductive tissues of
      many arthropod species. These bacteria are associated with reproductive
      alterations in their hosts, including parthenogenesis, reproductive
      incompatibility and feminization. A fine-scale phylogenetic analysis was done
      using DNA sequences from ftsZ, a rapidly evolving bacterial cell-cycle gene. ftsZ
      sequences were determined for 38 different Wolbachia strains from 31 different
      species of insects and one isopod. The following results were found: (i) there
      are two major division of Wolbachia (A and B) which diverged 58-67 millions years
      before present based upon synonymous substitution rates; (ii) a general
      concordance is found between the ftsZ and 16S rDNA phylogenies, indicating that
      these represent bacterial strain (rather than simply gene) phylogenies; however,
      a possible example of recombination between A and B division bacteria may have
      occurred in the feminizing Wolbachia present in an isopod; (iii) extensive
      horizontal transmission of Wolbachia has occurred between insect taxa, including
      different insect orders; one strain in particular (designated Adm) shows
      extensive recent horizontal transmission; (iv) there is an association between
      the Wolbachia found in a parasitic wasp (Nasonia) and its fly host
      (Protocalliphora), suggesting exchange of bacteria between these species; (v)
      parthenogenesis induction has evolved several times among the Wolbachia; and (vi)
      some insects harbour infections with more than one Wolbachia strain, even within
      individual insects.

PMID- 7644550
TI  - Functional mapping of the human colour centre with echo-planar magnetic resonance
      imaging.
AB  - Clinical studies of cerebral achromatopsia have suggested a colour centre in the
      human fusiform gyrus. By using functional magnetic resonance imaging, we examined
      whether the fusiform gyrus shows activity correlated with the perception of
      colour. We tested three stimulus conditions in which the subject maintained
      fixation: (i) a circular array of six coloured circles; (ii) the same as (i)
      except that each circle is equiluminant grey with its colour counterpart; and
      (iii) the same as (i) plus a clockwise shift of circles to neighbouring positions
      every 1 s. After termination of the stimulus, the subject perceived an after
      image of circles with complementary colours in (i), but not in (iii). In
      condition (i), we found a focal signal increase in the posterior part of the
      fusiform gyrus. In condition (ii), the activation in the same locus during the
      stimulation period was weaker than that in (i). In condition (iii), the signal
      intensity after termination of the stimulus was weaker than that in (i). The
      colour effect and after-effect on activation of the fusiform gyrus observed here
      suggest its critical role in human colour perception.

PMID- 7644551
TI  - Lipid studies in retinitis pigmentosa.

PMID- 7644552
TI  - Cytoplasmic fatty acid-binding proteins: their structure and genes.

PMID- 7644553
TI  - Heterogeneity in adipose tissue metabolism: causes, implications and management
      of regional adiposity.
AB  - The observation that different patterns of adipose tissue distribution are
      associated with different metabolic abnormalities, has recently given new impetus
      to research in obesity. Due to several methodologic problems, however, many
      aspects of regional excess of adipose tissue are still poorly understood. Among
      them, the causes and the metabolic consequences of regional adiposity are
      particularly important. Heterogeneity in adipose tissue distribution may be
      determined by a combination of genetic and hormonal causes. Both factors may
      determine differences in metabolism of various adipose tissue compartments
      primarily by regulating LPL production, storage and release of triacylglycerols,
      and aromatization of androgens. Furthermore, changes in adipocyte sensitivity to
      hormones such as, sex steroids, glucocorticoids, insulin and adrenergic hormones
      may also regulate fat distribution in various adipose tissue compartments. The
      metabolic heterogeneity of adipose tissue from various compartments, particularly
      the differences between the "portal" and subcutaneous adipose tissues, may
      account for several metabolic abnormalities associated with "upper body
      adiposity". However, no direct evidence is available to confirm this hypothesis.
      Recent advances in the methodology to study adipose tissue distribution (mainly
      CT and MRI) may provide the necessary tools to evaluate the true impact of
      adiposity in various compartments on intermediary metabolism and to identify a
      "morbid" adipose tissue compartment.  These observations may help in designing
      better therapeutic strategies targeted towards regional adiposity and its
      metabolic complications.

PMID- 7644554
TI  - The role of lipoprotein cholesterol in biliary steroid secretion. Studies with in
      vivo experimental models.

PMID- 7644555
TI  - Monthly prostaglandin bibliography prepared by the University of Sheffield
      Biomedical Information Service.

PMID- 7644556
TI  - The occurrence of prostaglandins and related compounds in lower organisms.

PMID- 7644557
TI  - Cyclosporin A inhibits leukotriene production in intact RBL-1 cells without
      inhibiting leukotriene biosynthetic enzymes.
AB  - The effects of cyclosporin A (CSA) on arachidonic acid (AA) metabolism were
      investigated in intact rat basophilic leukemia-1 (RBL-1) cells and cell lysates.
      Calcium ionophore (A23187)-stimulated synthesis of cysteinyl leukotrienes (LTC4,
      LTD4, and LTE4), LTB4, and 5-hydroxyeicosatetraenoic acid (5-HETE) in intact
      cells in the absence or presence of CSA was measured by reversed-phase high
      performance liquid chromatography (HPLC). CSA inhibited the production of
      cysteinyl LTs, LTB4, and 5-HETE in intact cells in a dose-dependent manner. The
      synthesis of cysteinyl LTs, LTB4, and 5-HETE was also measured after the
      incubation of cell lysates with free AA in the absence or presence of CSA. CSA
      did not inhibit synthesis of cysteinyl LTs, but rather stimulated production of
      LTB4 and 5-HETE in cell lysate. A23187-stimulated release of incorporated [3H]AA
      from intact cells was not inhibited by CSA. CSA did not inhibit the synthesis of
      cysteinyl LTs and LTB4 when cells incubated with LTA4 as the substrate. These
      results indicate that the inhibitory effects of CSA on the synthesis of LTs and 5
      HETE in intact cells are attributable to a modulatory action on a step in the
      series of intracellular events that includes the activation of 5-lipoxygenase,
      which are initiated by Ca2+ influx and end in the release of metabolites from the
      cell membrane, rather than to a direct inhibitory action on enzymes in the LT
      biosynthetic pathway.

PMID- 7644558
TI  - Inhaled nitric oxide reverses PAF-dependent bronchoconstriction in the pig.
AB  - In six anesthetized, paralyzed, mechanically ventilated pigs we evaluated the
      respiratory effects of inhaled nitric oxide (NO) (80 ppm in O2) under control
      conditions and after platelet-activating factor (PAF) administration (50 ng/kg,
      i.v.). PAF was also administered to the same pigs after pretreatment with
      indomethacin (3 mg/kg, i.v.). The mechanical properties of the respiratory system
      were evaluated by the rapid airway occlusion technique. With this technique the
      overall respiratory resistances, the airway resistances, and the additional
      resistances of respiratory system and lung can be evaluated. The results show
      that NO inhaled by the pig at 80 ppm for 6 min under control conditions reduced
      static and dynamic elastances of the respiratory system and lung and pulmonary
      arterial pressure, without modifying bronchomotor tone. Therefore, NO reduced the
      PAF-dependent changes in resistances and in static and dynamic elastances of the
      respiratory system and lung. The modest change in elastances caused by PAF in
      pigs pretreated with indomethacin was reduced by NO inhalation, which also has a
      mild bronchodilatory effect. The changes in elastances appear to be correlated
      with the pulmonary vasodilator activity of inhaled NO.

PMID- 7644559
TI  - Effects of indomethacin with or without linoleic acid on human breast cancer
      cells in vitro.
AB  - The effect of indomethacin (INDO) with or without the addition of linoleic acid
      (LA) was investigated in a cultured MDA-MB-231 human breast cancer cell line. It
      was found that INDO without LA suppressed cell growth and thymidine
      incorporation; however, with the addition of LA, INDO at low concentration
      promoted these factors, whereas INDO at higher concentrations suppressed them. On
      the other hand, INDO with or without the addition of LA reduced the secretion of
      prostaglandin E (PGE). However, INDO at a low concentration (1 microgram/ml) with
      the addition of LA increased the secretion of leukotriene B (LTB), while INDO
      without LA had no effect on the secretion of LTB. When the relationship between
      cell growth and PGE or LTB concentration was investigated, cell growth was
      associated with the PGE and LTB concentrations when the cells were treated with
      INDO and LA, whereas it was associated only with the PGE and LTB concentrations
      when the cells were treated with INDO and LA, whereas it was associated with the
      PGE concentration when they were treated with INDO alone.

PMID- 7644560
TI  - Essential fatty acid metabolism in patients with essential hypertension, diabetes
      mellitus and coronary heart disease.
AB  - Mortality and morbidity from coronary heart disease (CHD), diabetes mellitus (DM)
      and essential hypertension (HTN) are higher in people of South Asian descent than
      in other groups. There is evidence to believe that essential fatty acids (EFAs)
      and their metabolites may have a role in the pathobiology of CHD, DM and HTN.
      Fatty acid analysis of the plasma phospholipid fraction revealed that in CHD the
      levels of gamma-linolenic acid (GLA), arachidonic acid (AA), eicosapentaenoic
      acid (EPA) and docosahexaenoic acid (DHA) are low, in patients with HTN linoleic
      acid (LA) and AA are low, and in patients with non-insulin dependent diabetes
      mellitus (NIDDM) and diabetic nephropathy the levels of dihomo-gamma-linolenic
      acid (DGLA), AA, alpha-linolenic acid (ALA) and DHA are low, all compared to
      normal controls. These results are interesting since DGLA, AA and EPA form
      precursors to prostaglandin E1, (PGE1), prostacyclin (PGI2), and PGI3, which are
      potent platelet anti-aggregators and vasodilators and can prevent thrombosis and
      atherosclerosis. Further, the levels of lipid peroxides were found to be high in
      patients with CHD, HTN, NIDDM and diabetic nephropathy. These results suggest
      that increased formation of lipid peroxides and an alteration in the metabolism
      of EFAs are closely associated with CHD, HTN and NIDDM in Indians.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7644561
TI  - Cytoprotective and antisecretory activity of a ranitidine-zinc complex.
AB  - The effects of a ranitidine-zinc complex and ranitidine alone were compared in
      three different experimental models (pyloric ligation, ethanol and indomethacin)
      of gastric ulceration in the rat. In the pyloric ligation model, the ranitidine
      zinc complex (50, 100 and 150 mg/kg p.o.) showed antiulcerogenic activity similar
      to that observed with equimolar doses of ranitidine (35, 70 and 105 mg/kg p.o.).
      Both the ranitidine-zinc complex and ranitidine significantly reduced (p < 0.05)
      gastric acid secretion in a dose-dependent manner. The protective effect of the
      ranitidine-zinc complex (100 and 150 mg/kg p.o.) against gastric damage
      developing after p.o. administration of absolute ethanol or indomethacin was
      enhanced (p < 0.05) with respect to that obtained with equimolar doses of
      ranitidine (70 and 105 mg/kg p.o.). The presence of zinc in the ranitidine-zinc
      complex does not interfere with the antisecretory effects of ranitidine on the
      gastric mucosa, while it confers an additional cytoprotective action to the final
      compound.

PMID- 7644562
TI  - Dissimilarity between prostaglandin E1 and nitric oxide donors as potentiators of
      plasma exudation in the rabbit skin in vivo.
AB  - The ability of prostaglandin E1 (PGE1) and nitric oxide (NO) donor compounds such
      as sodium nitroprusside (SNP), glyceryl trinitrate (GTN), and 3-morpholino
      sydnonimine (SIN-1) to modulate the histamine- and bradykinin-induced increase in
      microvascular permeability have been investigated in rabbit skin. The effect of
      the NO synthesis inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) on the
      plasma exudation induced by histamine and bradykinin was also studied. Local
      edema formation was evaluated using [125I]human serum albumin. New Zealand white
      rabbits received an intravenous injection of [125I]human albumin followed
      immediately by the intradermal injection of edematogenic agents into the shaved
      dorsolateral skin. PGE1 (0.1 nmol/site) significantly potentiated both histamine-
      and bradykinin-induced edema. In contrast, SNP (0.4-400 nmol/site), SIN-1 (0.4
      400 nmol/site), and GTN (0.4-40 nmol/site) did not affect the edematogenic
      response induced by either histamine or bradykinin. GTN (0.4-40 nmol/site) also
      had no effect on the increase in plasma exudation induced by histamine and
      bradykinin in the presence of PGE1. L-NAME (50-400 nmol/site, but not its
      enantiomer D-NAME, dose-dependently reduced the edema formation induced by a
      combination of either histamine or bradykinin with PGE1. This inhibition was
      significantly reversed by SNP (4-400 nmol/site) and by high doses (2.5
      mumol/site) of L-arginine (but not by D-arginine). Our results thus demonstrate
      that PGE1, but not nitrovasodilators, can actually potentiate histamine- and
      bradykinin-induced edema in rabbit skin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7644563
TI  - Dose-dependent mediation of leukotriene D4-induced airway microvascular leakage
      and bronchoconstriction in the guinea pig.
AB  - The i.v. administration of leukotriene (LT)D4 to anesthetized guinea pigs
      produced dose-dependent increases in pulmonary microvascular permeability, as
      measured by extravasation of Evans blue dye into the trachea, main bronchi, and
      small airways, with an ED50 of approximately 0.05 microgram/kg. When LTD4 was
      administered at 0.3 microgram/kg, the resulting plasma extravasation into all
      three airway sections was markedly reduced by pretreatment with a cyclooxygenase
      inhibitor, meclofenamic acid (2.5 mg/kg, i.v.), a thromboxane (TX) receptor
      antagonist, SQ 29,548 (0.1 or 1 mg/kg, i.v.), or a peptidoleukotriene receptor
      antagonist, pranlukast (SB 205312) (0.1 or 1 mg/kg, i.v.), but not by the H1
      histamine receptor antagonist, pyrilamine. When LTD4 was administered at 1.0
      microgram/kg, meclofenamate (2.5 or 5 mg/kg, i.v.) or SQ 29,548 slightly
      attenuated plasma extravasation only in the small airway, whereas pranlukast was
      effective in all three airway segments. Administration of the 5-lipoxygenase
      inhibitor, zileuton (10 mg/kg, i.v.), or the PAF antagonist, L-659,989 (5 mg/kg,
      i.v.), did not affect the microvascular leakage response to 1.0 microgram/kg
      LTD4. In addition, i.v.-administered LTD4 (0.3 or 1.0 microgram/kg) or the
      prostaglandin (PG)/TXA2 receptor agonist, U-46619 (3.0 micrograms/kg), produced
      significant bronchoconstriction as measured by increases in pulmonary
      insufflation pressure. The bronchoconstrictor responses to LTD4 were markedly
      attenuated by the same inhibitors, namely meclofenamic acid, SQ 29,548, and
      pranlukast, that reduced the 0.3 microgram/kg LTD4-induced plasma extravasation
      throughout the airways and the 1.0 microgram/kg LTD4-induced extravasation into
      the small airways. U-46619-induced bronchoconstriction was blocked only by SQ
      29,548.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7644564
TI  - IL-3 and IL-5 enhance the production of LTB4 stimulated by calcium ionophore in
      rat basophilic leukemia cells.
AB  - To determine the regulatory mechanism of Leukotriene (LT) B4 synthesis by
      cytokines, we investigated the regulation of LTB4 generation by short-term (30
      min) priming and long-term (15 h) enzyme-inducing actions of the four cytokines
      interleukin (IL)-3, IL-5, tumor necrosis factor alpha (TNF-alpha), and
      transforming growth factor alpha (TGF-alpha) in rat basophilic leukemia-1 (RBL-1)
      cells. Pretreatment of cells with IL-3 or IL-5 for 30 min increased A23187-
      (5x10(-9)M) stimulated synthesis of LTB4 by three to four times over control
      levels. However, IL-3 or IL-5 lacked this effect when stimulated with exogenous
      arachidonic acid A at 10(-4)M. TNF-alpha and TGF-alpha had no priming effect on
      LTB4 synthesis following stimulation with either A23187 (5x10(-9)M) or AA(10(
      4)M). Stimulation with the calcium ionophore (A23187)(10(-5)M) or AA(10(-4)M)
      following 15-h exposure to these cytokines had no effect. These results suggest
      that IL-3 and IL-5 increase the production of LTB4 by priming the activity of
      phospholipase A2(PLA2) without inducing enzymes in the arachidonate 5
      lipoxygenase pathway. Such a priming effect may be important in regulating the
      development of allergic and other diseases involving the inflammatory reaction.

PMID- 7644566
TI  - Genotoxicity, carcinogenicity and acid-suppressing medications.
AB  - With the availability of increasingly potent acid-suppressing medications,
      questions continue to rise concerning the safety of these compounds in regards to
      carcinogenetic potential. In this review, we examine current concepts and
      procedures relating to genotoxicity, the potential for a chemical agent to
      interact with and alter the genomic information of the cell, and carcinogenesis.
      A description and discussion of commonly utilized techniques for the
      determination of (a) in vitro mutagenicity, (b) in vitro and in vivo DNA damage
      and repair, (c) in vitro and in vivo chromosomal damage and (d) chronically dosed
      animal tumorigenesis development is presented. Observations from these procedures
      as they have been applied to a review of the safety of acid-suppressing
      medications will be discussed. An evaluation of reports relating to potential
      genotoxic and carcinogenic hazards of therapeutically relevant acid-suppressing
      medications (cimetidine, ranitidine, omeprazole) is presented. Information
      related to the effect of prolonged administration of acid-suppressing
      medications, alterations of serum gastrin levels, and the potential for tumor
      promotion is discussed.

PMID- 7644567
TI  - 5-Hydroxytryptamine-interacting drugs in animal models of anxiety disorders: more
      than 30 years of research.
AB  - An overview of the behavioral data arising from the vast literature concerning
      the involvement of 5-hydroxytryptamine (5-HT) neurotransmission in the regulation
      of anxiety is presented. More than 1300 experiments were carried out in this area
      and they provide evidence that: (1) results obtained in ethologically based
      animal models of anxiety with drugs stimulating 5-HT transmission are most
      consistent with the classic 5-HT hypothesis of anxiety in that they show an
      increase in animals' emotional reactivity; (2) no category of anti-anxiety models
      are selectively sensitive to the anxiolytic-like effects of drugs targetting 5
      HT1A, 5-HT2A or 5-HT2C receptor subtypes; (3) anxiolytic-like effects of 5-HT3
      receptor antagonists, in the great part, are revealed by models based on
      spontaneous behaviors. Taken together, these observations lead to the conclusion
      that different 5-HT mechanisms, mediated by different receptor subtypes, are
      involved in the genesis of anxiety.

PMID- 7644565
TI  - Interleukin-1 in the treatment of cancer.
AB  - Interleukin-1 (IL-1) is a cytokine with many activities central to immune
      function and hematopoiesis. Many IL-1 properties can be potentially exploited in
      the treatment of malignancy. This review describes the toxicities and antitumor
      effects observed in Phase I and II trials of IL-1 in cancer patients. The
      immunophysiology and the induction of cytokines by IL-1 has been examined in many
      of the Phase I trials and has aided in understanding IL-1 effects in humans. The
      influence of IL-1 on granulopoiesis and thrombopoiesis when given by different
      regimes is also reviewed in detail.

PMID- 7644568
TI  - Central nervous system pharmacology of neuropeptide Y.
AB  - Neuropeptide Y (NPY) is a 36-amino acid peptide belonging to the pancreatic
      polypeptide family that has marked and diverse biological activity across
      species. NPY originally was isolated from mammalian brain tissue somewhat more
      than 10 years ago and, since that time, has been the subject of numerous
      scientific publications. NPY and its proposed three receptors (Y1, Y2 and Y3) are
      relatively abundant in and uniquely distributed throughout the brain and spinal
      cord. This review will highlight the results from a number of research-oriented
      studies that have examined how NPY is involved in CNS function and behavior, and
      how these studies may relate to the possible development of medicines, either NPY
      like agonists or antagonists, directed towards the treatment of disorders such as
      anxiety, pain, hypertension, schizophrenia, memory dysfunction, abnormal eating
      behavior and depression.

PMID- 7644569
TI  - Identity and pretense.

PMID- 7644570
TI  - Effects of quadriceps femoris muscle strengthening on crouch gait in children
      with spastic diplegia.
AB  - BACKGROUND AND PURPOSE: Despite evidence of weakness in children with cerebral
      palsy, the use of strength training in this population remains controversial.
      SUBJECTS: Fourteen children with spastic diplegia, ranging in age from 6 to 14
      years (X = 9.1, SD = 2.5), participated in a bilateral quadriceps femoris muscle
      strengthening program. METHODS: The children exercised three times per week for 6
      weeks using ankle weights at loads of approximately 65% of each child's maximum
      isotonic force production. The maximal voluntary contraction of the quadriceps
      femoris muscles was measured before, at the midpoint of, and immediately
      following the exercise program at 30, 60, and 90 degrees of knee flexion. Gait
      analyses were performed before and after the strengthening program to determine
      whether quadriceps femoris muscle strengthening influenced gait. RESULTS:
      Children with spastic diplegia can increase quadriceps femoris muscle strength
      through heavy resistance exercise. Repeated-measures analysis of variance and
      multivariate analysis of variance procedures were used to assess changes in force
      and in gait variables. Improvement in the degree of crouch at initial floor
      contact at the freely selected speed and an increase in stride length at free and
      fast speeds were found. CONCLUSION AND DISCUSSION: These findings suggest that
      resistance exercise is an effective treatment strategy and as such should be
      considered as one component in the habilitation of children with cerebral palsy.

PMID- 7644571
TI  - Vastus medialis oblique/vastus lateralis muscle activity ratios for selected
      exercises in persons with and without patellofemoral pain syndrome.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to determine which of
      selected exercises with and without the feet free to move would enhance vastus
      medialis oblique muscle (VMO) activity over that of the vastus lateralis muscle
      (VL) and whether the use of taping would increase VMO activity. SUBJECTS: Twenty
      one subjects without patellofemoral pain (PFP) syndrome and 10 subjects with PFP
      syndrome, aged 19 to 43 years (X = 26, SD = 7), participated. METHODS: Subjects
      were studied for the normalized, integrated electromyographic (IEMG) activity of
      their VMO, VL, and adductor magnus muscle (subjects without PFP syndrome) and the
      VMO/VL ratio using wire electrodes. RESULTS: One exercise demonstrated greater
      activation of the VMO over the VL when compared with similar exercises in
      subjects without PFP syndrome. The mean VMO/VL activity ratio for terminal knee
      extension was 1.2 (SD = 0.5) with the hip medially rotated and 1.0 (SD = 0.4)
      with the hip laterally rotated. Although subjects reported that patellar taping
      decreased pain 94% during the step-down exercise, the VMO/VL ratio was not
      changed. CONCLUSION AND DISCUSSION: The results suggest that neither exercises
      purported to selectively activate VMO activity nor patellar taping improve the
      VMO/VL ratio over similar exercises.

PMID- 7644572
TI  - Relationship of plantar-flexor peak torque and dorsiflexion range of motion to
      kinetic variables during walking.
AB  - BACKGROUND AND PURPOSE: Limited ankle plantar-flexor moments and power during
      walking have been documented in several patient populations and are believed to
      contribute to gait deviations. The primary purpose of this study was to determine
      the relationship of plantar-flexor peak torque (PFPT) and dorsiflexion range of
      motion (ROM) to peak ankle moments and power during walking in a group of
      subjects without diabetes mellitus (DM) and in a group of subjects with DM and
      associated peripheral neuropathies. SUBJECTS: Nineteen subjects, 9 with DM and
      associated peripheral neuropathies (mean age = 58 years, SD = 14, range = 35-75
      years) and 10 without DM (mean age = 57 years, SD = 11, range = 37-68 years),
      were evaluated. METHODS: The following data were collected on all subjects: PFPT,
      dorsiflexion ROM, and ankle moments and power during walking (using a two
      dimensional link-segment model). Hierarchical multiple regression was used for
      data analysis. RESULTS: Plantar-flexor peak torque made substantial contributions
      to the ankle moment (40%) and ankle plantar-flexor power (53%) during walking.
      There also was a high correlation between PFPT and dorsiflexion ROM (r = .78) and
      between dorsiflexion ROM and ankle power (r = .72). CONCLUSION AND DISCUSSION:
      Plantar-flexor peak torque and dorsiflexion ROM are interrelated and appear to be
      important factors that contribute to ankle plantar-flexor moments and power
      during walking. This finding suggests that increasing PFPT and dorsiflexion ROM
      may help decrease gait deviations such as decreased step length and walking
      speed. When increasing PFPT is not possible, the natural occurrence of limited
      dorsiflexion ROM may help to maximize ankle moments during walking. Further
      research is needed to test whether these proposed treatment strategies can have a
      clinically useful effect. [Mueller MJ, Minor SD, Schaaf JA, et al. Relationship
      of plantar-flexor peak torque and dorsiflexion range of motion to kinetic
      variables during walking.

PMID- 7644573
TI  - The standing heel-rise test for ankle plantar flexion: criterion for normal.
AB  - BACKGROUND AND PURPOSE: Manual muscle testing with the examiner providing the
      resistance has long been a standard test of muscle strength. Through the use of
      extremities acting as levers, clinicians have been able to effectively apply
      resistance to all muscle groups except the ankle plantar flexors. As a result, a
      standing heel-rise test that uses body weight as the resistance has been
      substituted. The number of heel-rises that represent normal plantar-flexor
      "strength" and the ability of subjects to repeatedly use that "strength" remain
      unresolved. Because walking is an endurance task, the hypothesis tested by this
      study was that individuals without known weakness would be able to perform more
      than the standard recommended one to five standing heel-rises. The purpose of
      this study was to measure the number of standing heel-rises that individuals
      without known weakness could accomplish. SUBJECTS: Two hundred three subjects
      were studied for their ability to do standing heel-rises, as is done when testing
      plantar-flexion strength using the upright test. There were 122 male subjects and
      81 female subjects, ranging in age from 20 to 59 years. METHODS: Each subject was
      asked to do as many standing heel-rises as he or she could, with careful
      monitoring of body and limb alignment and of ankle motion, with specific criteria
      for stopping. RESULTS: The average number of heel-rises was 27.9 (SD = 11.1,
      minimum = 6, maximum = 70) for all groups and both genders, with no differences
      between male and female subjects. The lower 99% confidence interval was 25.
      CONCLUSION AND DISCUSSION: A recommendation is made to change the standard of
      testing plantar-flexion function, when using the standing heel-rise test, to
      require 25 repetitions for a grade of Normal. [Lunsford BR, Perry J. The standing
      heel-rise test for ankle plantar flexion: criterion for normal.

PMID- 7644574
TI  - Changes in the mean center of balance during balance testing in young adults.
AB  - BACKGROUND AND PURPOSE: The analysis of standing balance is now possible using
      commercially available force platforms. In order to establish appropriate testing
      and treatment protocols for patient populations, we contend data should be
      collected relative to the typical response of nonpatient groups. More
      importantly, we need to better understand response characteristics of persons
      with intact nervous systems. The purpose of this study was to evaluate the
      typical response of young adults without known musculoskeletal or neurological
      impairments to balance testing with the Balance System. SUBJECTS: Sixty-six
      subjects without known impairments (mean age = 23.6 years, SD = 4.5, range = 21
      47) were evaluated in a single testing session. METHODS: Center of balance (COB),
      a vertical force measurement, was evaluated under each of 18 conditions: 2 visual
      conditions (eyes open, eyes closed), 3 platform conditions (stable, vertical
      tilt, linear translation), and 3 foot positions (apart, together, tandem).
      RESULTS: An effect was found for average displacement to the left along the x
      axis under all testing conditions. The COB locus along the y axis was dependent
      on the foot position, platform condition, and visual condition. CONCLUSION AND
      DISCUSSION: Movement of the COB toward the center of the base of support
      accompanied closing of the eyes, narrowing of the base of support, and movement
      of the support surface. These findings are consistent with the need to move the
      center of gravity away from the limits of stability under more challenging stance
      conditions. This study contributes to the existing knowledge base related to
      standing balance function in young adults without musculoskeletal or neurological
      impairments and provides data that can be used for criterion-based comparisons of
      young adult patients. [Nichols DS, Glenn TM, Hutchinson KJ. Changes in the mean
      center of pressure during balance testing.

PMID- 7644575
TI  - A guide to physical therapist practice, Volume I: A description of patient
      management. American Physical Therapy Association.

PMID- 7644576
TI  - Cumulation of knowledge.

PMID- 7644577
TI  - Burn care.

PMID- 7644578
TI  - Freedom to choose.

PMID- 7644579
TI  - In search of the grail.

PMID- 7644580
TI  - Understanding the Biological Clock: From Genetics to Physiology. APS conference.
      Hanover, New Hampshire, July 8-12, 1995. Abstracts.

PMID- 7644581
TI  - Citation statistics for the individual journals of the American Journal of
      Physiology.

PMID- 7644582
TI  - [Biological and family factors in the chronicity of childhood depression.
      Longitudinal study].
AB  - A prospective follow-up study was conducted of a group of 32 children diagnosed
      at 7 years of age as socially and emotionally immature and depressive. In the
      three year follow-up a group found still depressive was compared with those no
      longer depressive. Biological vulnerability, early childhood development, family
      internal and external boundaries and child relational individuation were taken
      into account. Chronicity of childhood depression can be related to vulnerability
      and to family disfunction. Mutual interrelation of those factors requires further
      studies.

PMID- 7644584
TI  - [Incest as one of the forms of child sexual abuse].

PMID- 7644583
TI  - [Analysis of psychiatric diagnoses in children with anxiety symptoms].

PMID- 7644585
TI  - [Twin rivalry as an important factor in the development of anorexia nervosa in a
      14-year-old girl].

PMID- 7644587
TI  - [Differential diagnosis between the hysteric syndrome and paranoid syndrome in
      adolescents].

PMID- 7644588
TI  - [Hysterical syndrome after abatement of paranoid syndrome].

PMID- 7644586
TI  - [The application of narcoanalysis in bulimia nervosa: a case report].

PMID- 7644589
TI  - [Pathogenetic mechanisms of stress in endogenous diseases].

PMID- 7644590
TI  - [A comparison between subjective time estimation and simple reaction time in
      patients with endogenous depression and in healthy subjects].

PMID- 7644591
TI  - [Preliminary results of the study on the combined treatment of endogenous
      depression].

PMID- 7644592
TI  - [Post-stroke depression].

PMID- 7644593
TI  - [The current status of mental health care in the United States].

PMID- 7644594
TI  - An interview with Clifford Scott. Interview by Virginia Hunter.

PMID- 7644595
TI  - Hypnotically recalling dreams during analysis.
AB  - This study described the procedure, the theoretical rationale, and clinical
      material relating to the hypnotic recalling of dreams during periods of
      protracted "dreamless" analyses. Two clinical examples were used to demonstrate
      the efficacy of using a special hypnotic procedure close to the analytic free
      association method for the remembering or recalling the dreams. Discussion of the
      clinical material found: 1. the main factors contributing to a "dreamless"
      analysis were to be found in the transference-countertransference resistances of
      the analysis; 2. the justification for introducing the special hypnotic procedure
      as a parameter in the analysis was discussed and confirmed; 3. the remembering
      recalling of the first dream--following the hypnotic intervention--lead to the
      recovery of a critical childhood memory; and 4. the parameter of using hypnosis
      as a method of breaking the intractable resistance of a "dreamless" analysis did
      not become an alien force which intervened whenever strong resistances appeared.
      On the contrary, it seemed to serve as a temporary therapeutic mechanism for
      allowing an energy shift to occur in the all-or-none defensive state of a
      "dreamless" analysis.

PMID- 7644596
TI  - Projective identification and countertransference interventions: since feeling is
      first.

PMID- 7644597
TI  - The Bobbitt case and the quest for a good-enough penis.

PMID- 7644598
TI  - Ownership of the body and mind: developmental considerations for adult
      psychoanalytic treatment.

PMID- 7644599
TI  - A note on Sandor Ferenczi and the Dionysian itinerary in psychoanalysis.

PMID- 7644601
TI  - The grandiose character, primary type.
AB  - In this article I have elucidated the diagnostic entity of the grandiose
      character, primary type. The concept of the primary grandiose character has been
      around for a long time but has not been formally elucidated. The primary
      grandiose character is contrasted to the reactive grandiose character, which is
      the type normally considered in the literature. The primary grandiose character
      is someone who was treated with such anticipation and succor by the parents that
      he learned to feel no way but good and to demand succor when he did not feel
      good. The reactive grandiose character is someone who originally moderated his
      primary grandiosity but re-intensified it in order to defend against later
      appearing pain, particularly of a narcissistic sort. The primary grandiose
      character develops a large array of fears and depressions as he learns little
      developmentally except how to demand. In the face of these increasing anxieties
      and depressions, he simply demands more and more. When he appears in treatment,
      he shows himself as an anxiety- and depression-ridden individual, with a strong
      need for help (succor). The analyst tries to help with the anxieties and
      depressions but the treatment goes round and round because the patient does not
      cathect the observing function of his own ego, only that of the analyst's ego:
      the analyst is to know what is wrong (observe it) and fix it. When the analyst
      does not fix it (although he might, for a while, observe it), the analysand's
      grandiose rage breaks through and he shows himself for what he is, a grandiose
      character, primary type. Now the task is clear but the treatment formidable. The
      analysand must come to observe that he is grandiose and that he has foresworn the
      observing function. This process, which comprises a major portion of the working
      through, is replete with grandiose rage, working through, grandiose rage, and
      working through. Ultimately the patient discovers the great strength that comes
      from decreased reliance on the observing ego of others and increased reliance on
      his own observing ego. A number of diagnostic entities and clinical behaviors are
      shown to have a primary grandiose base. And rather than some of these depending
      upon repression as the basic defense, it would seem that they depend on a pre
      stage of repression, akin to the concept of biological irritability. The concepts
      of secondary grandiosity, partial grandiosity, and developmental grandiosity are
      natural corollaries to the concept of primary grandiosity.

PMID- 7644600
TI  - The entangled self: style and the unconscious in the work of Thomas Bernhard.

PMID- 7644602
TI  - Interrelatedness of marital relations and parent-child relations: a meta-analytic
      review.
AB  - It is widely assumed that a linkage, crucial to the understanding of child
      behavior, exists between marital and parent-child relationship quality. A meta
      analysis of 68 studies was conducted to determine whether this linkage exists
      and, if so, whether the linkage is positive (as suggested by the spill-over
      hypothesis) or negative (as suggested by the compensatory hypothesis). Results
      supported the spillover hypothesis; a positive and nonhomogeneous effect size of
      moderate magnitude was found (d = 0.46). This suggests that research in this area
      can move beyond the question of whether a positive or negative association exists
      to identifying moderators of the association. Examination of the impact of 13
      potential moderators did not support the existence of any of these variables that
      could be adequately examined. This suggests that the link between marital and
      parent-child relations functions as a more stable force than previously thought.

PMID- 7644603
TI  - What proverb understanding reveals about how people think.
AB  - The ability to understand proverbial sayings, such as a rolling stone gathers no
      moss, has been of great interest to researchers in many areas of psychology. Most
      psychologists assume that understanding the figurative meanings of proverbs
      requires various kinds of higher order cognitive abilities. The authors review
      the findings on proverb interpretation to examine the question of what proverb
      use and understanding reveals about the ways normal and dysfunctional individuals
      think. The widely held idea that failure to provide a figurative interpretation
      of a proverb necessarily reflects a deficit in specialized abstract thinking is
      rejected. Moreover, the ability to correctly explain what a proverb means does
      not necessarily imply that an individual can think abstractly. Various empirical
      evidence, nonetheless, suggests that the ability to understand many proverbs
      reveals the presence of metaphorical schemes that are ubiquitous in everyday
      thought.

PMID- 7644604
TI  - The longitudinal course of marital quality and stability: a review of theory,
      method, and research.
AB  - Although much has been learned from cross-sectional research on marriage, an
      understanding of how marriages develop, succeed, and fail is best achieved with
      longitudinal data. In view of growing interest in longitudinal research on
      marriage, the authors reviewed and evaluated the literature on how the quality
      and stability of marriages change over time. First, prevailing theoretical
      perspectives are examined for their ability to explain change in marital quality
      and stability. Second, the methods and findings of 115 longitudinal studies-
      representing over 45,000 marriages--are summarized and evaluated, yielding
      specific suggestions for improving this research, Finally, a model is outlined
      that integrates the strengths of previous theories of marriage, accounts for
      established findings, and indicates new directions for research on how marriages
      change.

PMID- 7644605
TI  - Determinants of negative priming.
AB  - The negative priming task is widely used to investigate attentional inhibition. A
      critical review of the negative priming literature considers various parameters
      of the task (e.g., time course, relation to interference, level of occurence, and
      susceptibility to changes in task context). It takes into account life span data
      and the performance of patients diagnosed with schizophrenia. On these bases, the
      review suggests that negative priming can be produced by 2 mechanisms: memorial
      and inhibitory. With respect to inhibition, the review suggests that (a) there
      are 2 systems, one responsible for identity and the other for location
      information; and (b) inhibition is a flexible, postselection process operating to
      prevent recently rejected information from quickly regaining access to effectors,
      thus helping to establish coherence among selected thought and action streams.

PMID- 7644606
TI  - Human behavioral sex differences: a role for gonadal hormones during early
      development?
AB  - Evidence that gonadal hormones during prenatal and neonatal development influence
      behavior is reviewed. Several theoretical models of hormonal influences, derived
      from research in other species, are described. These models are evaluated on the
      basis of data from humans with either normal or abnormal hormonal exposure. It is
      concluded that the evidence is insufficient to determine which model best
      explains the data. Sexual differentiation may involve several dimensions, and
      different models may apply to different behaviors. Gonadal hormones appear to
      influence development of some human behaviors that show sex differences. The
      evidence is strongest for childhood play behavior and is relatively strong for
      sexual orientation and tendencies toward aggression. Also, high levels of
      hormones do not enhance intelligence, although a minimum level may be needed for
      optimal development of some cognitive processes. Directions for future research
      are proposed.

PMID- 7644608
TI  - Addressing the needs of elderly radiology patients.
AB  - Elderly patients have special needs when undergoing radiographic examinations.
      This article describes three approaches radiologic technologists may use to meet
      those needs: a gerontologic approach for the well elderly, a geriatric approach
      for the frail elderly, and a number of departmental adaptations for all older
      patients. A well-defined science of patient care that includes knowledge of the
      elderly is essential to the continued growth of the profession of radiography.

PMID- 7644609
TI  - Implementing career ladders in diagnostic radiography.
AB  - The higher status and salary given to "special" imaging practitioners within the
      profession seems to diminish the role of the diagnostic radiographer. The upward
      mobility made possible by movement into newer imaging modalities has driven many
      of the best practitioners away from diagnostic radiography, even if they enjoy it
      or prefer it. In addition, today's reforms call for "multimodality"
      practitioners. The career ladder concept may be solution to these issues.

PMID- 7644607
TI  - The life of Ed C. Jerman: a historical perspective.
AB  - During radiology's early years, many people dedicated their lives to developing
      practical applications for the x-ray. A leader among them was Ed C. Jerman,
      author of the first textbook on radiographic technique and founder of the
      organization known today as the American Society of Radiologic Technologists.
      Through the first three decades of this century, Jerman worked diligently to
      bring legitimacy, organization and technical expertise to the fledgling
      profession of radiologic technology. In 1995, the centennial of the x-ray's
      discovery, it is appropriate to reflect on the many contributions of the man who
      is remembered today as the father of modern radiologic technology.

PMID- 7644610
TI  - The evolution of x-ray technique.

PMID- 7644611
TI  - Farewell essentials; hello standards.

PMID- 7644612
TI  - Diagnosis and treatment of colon cancer.

PMID- 7644613
TI  - This mammogram is brought to you by....

PMID- 7644615
TI  - ARRT history lesson.

PMID- 7644614
TI  - What is dose area product?

PMID- 7644616
TI  - The malpractice issue. Part II. Solutions.

PMID- 7644617
TI  - MR imaging of the breast.
AB  - Studies suggest that magnetic resonance (MR) imaging may have a variety of roles
      in the detection and management of breast disease. However, because study methods
      and imaging techniques are not standard, there is still a great deal of
      uncertainty about its place in clinical practice. The authors review the current
      state of breast MR imaging and address a number of issues, including the basis
      for contrast material-enhanced imaging, techniques, and possible clinical roles,
      including treatment planning, evaluation of the posttreatment breast, evaluation
      of breast implants, characterization of breast masses, MR imaging-guided biopsy,
      and the potential for cancer screening. Although it is premature to recommend the
      routine use of breast MR imaging, contrast-enhanced MR imaging has potential as a
      comprehensive platform for the detection, localization, biopsy, and treatment of
      breast cancers.

PMID- 7644618
TI  - Detection of renal artery stenosis with Doppler sonography: it is more
      complicated than originally thought.

PMID- 7644619
TI  - Physicians as judicial hangmen.

PMID- 7644620
TI  - Error patterns in the MR imaging evaluation of menisci of the knee.
AB  - PURPOSE: To categorize errors in interpretation of magnetic resonance (MR) images
      of the knee and explain the discrepancy between MR imaging and diagnostic
      arthroscopic findings. MATERIALS AND METHODS: Five hundred sixty-one patients
      underwent arthroscopy and MR imaging of the knee. Prospective and retrospective
      readings were used to categorize tear type and location. Sixty-six patients had
      68 discrepancies between MR imaging and arthroscopic findings. RESULTS:
      Prospective interpretation of MR images of the lateral meniscus had a sensitivity
      of 82%, specificity of 98%, and accuracy of 93%. For images of the medial
      meniscus, sensitivity was 96%; specificity, 91%; and accuracy, 95%. The number of
      diagnostic errors at retrospective analysis was 76% (n = 52) of the number at
      prospective analysis. CONCLUSION: MR imaging is accurate in evaluation for
      meniscal tears. Most errors in interpretation that occur at prospective
      evaluation also occur at retrospective evaluation. Some false-positive errors may
      be related to incomplete arthroscopic evaluation of the meniscus and confusion
      between what represents fraying and what represents a tear.

PMID- 7644621
TI  - Plantar compartments of the foot: MR appearance in cadavers and diabetic
      patients.
AB  - PURPOSE: To demonstrate the plantar compartments of the foot on magnetic
      resonance (MR) images. MATERIALS AND METHODS: The plantar compartments of four
      cadaveric feet underwent MR imaging and were sectioned. Fifteen MR studies in 11
      patients with compartmental fluid were evaluated. The epicenter of infection was
      determined from review of the history, radiographs, and MR images. RESULTS: In
      the cadaveric feet, distribution of contrast material conformed to the
      compartmental anatomic features. MR findings in the specimen correlated exactly
      with gross findings. All seven feet with infection centered at the second through
      fourth metatarsal heads demonstrated only central compartment fluid. In seven of
      eight feet with a more medial or lateral epicenter of infection, fluid was seen
      in the lateral or medial compartment and in the central compartment. In one foot
      with a lateral epicenter of infection, fluid was confined to the lateral
      compartment. CONCLUSION: MR imaging accurately depicts the compartmental anatomic
      features of the foot.

PMID- 7644622
TI  - Osteoporosis: clinical assessment with quantitative MR imaging in diagnosis.
AB  - PURPOSE: To determine if the magnetic resonance (MR) imaging effective transverse
      relaxation rate (R2*) of trabecular bone marrow is lowered in osteoporosis.
      MATERIALS AND METHODS: R2* was measured in 146 women. Control subjects (n = 77;
      mean age, 46.6 years) had high mean spinal bone mineral densities (BMDs) and no
      vertebral deformities. Patients with spinal osteoporosis (n = 59; mean age, 59.7
      years) had at least one thoracic vertebral deformity and/or low BMDs. RESULTS:
      R2* was lower in patients for L-2 through L-5 (P < .001). Average R2* of L-3
      through L-5 (R2*av) was the best discriminator (64.79 sec-1 +/- 1.18 [standard
      error] for control subjects vs 53.39 sec-1 +/- 1.24 for patients; P < .0001).
      R2*av decreased with age in control subjects. The difference in R2*av in a subset
      of 38 age-matched pairs of patients and control subjects was 8.25 sec-1 (P <
      .0001). Subjects with deformities had lower 52*av than did control subjects (52.3
      sec-1 +/- 1.6 vs 62.5 sec-1 +/- 1.1, P < .0001). R2*av was correlated with mean
      BMD (r = .54, P < .0001). CONCLUSION: Patients with osteoporosis have lower R2*s
      in vertebral marrow.

PMID- 7644623
TI  - Bone loss in patients with chronic renal disease: prediction with quantitative
      bone scintigraphy with SPECT.
AB  - PURPOSE: To determine whether quantitative bone scintigraphy (QBS) with single
      energy photon emission computed tomography (SPECT) can help predict which
      patients with chronic renal disease will show bone mineral density (BMD) loss.
      MATERIALS AND METHODS: In 18 patients, the percentage of injected dose of
      technetium-99m methylene diphosphonate per cubic centimeter of bone was measured
      with QBS SPECT in the lumbar vertebrae and femoral neck. The differences in BMD
      over an average of 20 months were measured and compared with SPECT measurements.
      QBS values were also compared with serum bone turnover markers. RESULTS: There
      was a negative correlation (r = -.54, P < .05 for the lumbar spine and r = -.60,
      P < .01 for the femoral neck) between QBS values and bone loss. Positive and
      negative predictive values, sensitivity, and specificity of QBS for bone loss in
      the lumbar spine were 78%, 71%, 78%, and 71%, respectively, and in the femoral
      neck, 82%, 100%, 100%, and 78%, respectively. Differences between predictive
      values of serum bone turnover markers were not statistically significant.
      CONCLUSION: QBS with SPECT enabled prediction of rapid bone loss in patients with
      renal disease.

PMID- 7644624
TI  - Quantification of inflammation in the wrist with gadolinium-enhanced MR imaging
      and PET with 2-[F-18]-fluoro-2-deoxy-D-glucose.
AB  - PURPOSE: To quantify the activity of joint inflammation with magnetic resonance
      (MR) imaging and positron emission tomography (PET). MATERIALS AND METHODS:
      Gadolinium-enhanced MR imaging and 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG)
      PET of the wrist were performed prospectively in 12 patients receiving
      antiinflammatory therapy. Patients were studied three times: off medications for
      2 weeks, after 2 weeks of treatment with prednisone or nonsteroid
      antiinflammatory drugs, and after 12 weeks of treatment with methotrexate. Volume
      of enhancing pannus (VEP) was determined from fat-suppressed MR images (12
      patients). FDG uptake was calculated from PET images (11 patients). RESULTS: VEP
      and FDG uptake were closely correlated (r > .86, P < .0001), as were changes in
      VEP and standardized uptake volume (r > .91, P < .0002). VEP and FDG uptake were
      strongly associated with clinical findings in wrists (P < .002) but not with
      treatment outcomes (P > .05). CONCLUSION: Contrast material-enhanced MR imaging
      and PET allow quantification of volumetric and metabolic changes in joint
      inflammation and comparison of efficacies of antiinflammatory drugs.

PMID- 7644625
TI  - Massive osteoarticular knee allografts: structural changes evaluated with CT.
AB  - PURPOSE: To analyze the structural changes seen at computed tomography (CT),
      particularly the findings that precede insufficiency (fatigue) fractures in
      massive osteoarticular knee allografts. MATERIALS AND METHODS: The subchondral
      and cancellous bone of 12 allografts were retrospectively evaluated with repeat
      transaxial CT (mean follow-up, 53 months). RESULTS: Early cortical graft
      resorption was followed by slow thickening after 6 months. Formation of
      resorptive cysts increased the cortical irregularity, which leveled off after 2
      years. Late remodeling was evident as a subcortical sclerotic rim, "neocortex."
      Initially, the cancellous graft bone showed higher attenuation than the host
      bone; this difference subsided gradually during the first 3 years. Four
      insufficiency fractures were detected after the 1st postoperative year. Poor
      remodeling preceded these fractures. CONCLUSION: CT effectively depicted the
      structural changes during allograft incorporation and was superior to plain
      radiography for the detection of insufficiency fractures. The use of CT for
      follow-up of massive osteoarticular knee allografts provides additional
      information concerning the readiness of the graft for weight bearing.

PMID- 7644626
TI  - Bosentan, an orally active endothelin antagonist: effect on the renal response to
      contrast media.
AB  - PURPOSE: To examine the effect of bosentan, an orally active endothelin-receptor
      antagonist, on the renal response to contrast media in the isolated perfused rat
      kidney (IPRK) and to establish whether bosentan can inhibit contrast media
      induced nephrotoxicity in a multiple-insult model in the conscious rat. MATERIALS
      AND METHODS: Renal function was measured in the IPRK (n = 24) and in the rats
      that had undergone unilateral nephrectomy, were maintained on a salt-free diet,
      and were receiving indomethacin (10 mg/kg/d; n = 60). RESULTS: In the IPRK,
      diatrizoate and iotrolan reduced the glomerular filtration rate and renal
      perfusate flow, an effect markedly inhibited by bosentan (n = 6 per group). In
      the multiple-insult rat model, the fall in creatinine clearance produced by
      diatrizoate was also markedly inhibited by bosentan (n = 15 per group).
      CONCLUSION: Endothelin antagonists such as bosentan may be used to reduce the
      prevalence of contrast-induced nephrotoxicity.

PMID- 7644627
TI  - Normal renal artery spectral Doppler waveform: a closer look.
AB  - PURPOSE: To characterize the spectral Doppler tracing of the normal renal artery.
      MATERIALS AND METHODS: Doppler tracings were obtained from a phantom of a vessel
      with variable compliance and from the kidneys of 15 healthy volunteers. RESULTS:
      In the phantom, vascular compliance had the following effects on systolic flow
      velocity patterns: low compliance, little change in the sharp appearance of the
      systolic component of the transmitted pulse; mildly increased compliance, down
      stream dampening of early systolic acceleration (ESA) with the appearance of a
      sharp early systolic transmitted peak and of a more rounded late systolic
      compliance peak; high compliance, delayed and diminished transmitted peak that
      eventually disappeared within the enlarging down-stream compliance peak. Healthy
      subjects with compliant vessels had greater ESA and more frequently visualized
      early systolic peaks in the renal hilum than in the renal sinus. CONCLUSION:
      Absence of a discrete early systolic peak is a normal finding in young patients,
      especially in the more distal interlobar arteries. Loss of the early systolic
      peak may be explained on the basis of vascular compliance.

PMID- 7644629
TI  - Renal arteries: evaluation with optimized 2D and 3D time-of-flight MR
      angiography.
AB  - PURPOSE: To compare two-dimensional (2D) and three-dimensional (3D) time-of
      flight (TOF) techniques in magnetic resonance (MR) angiography of renal arteries.
      MATERIALS AND METHODS: In 46 patients, MR angiography was performed with 3D
      tilted optimized non-saturating excitation (TONE), 3D fast imaging with steady
      precession (FISP), and 2D fast low-angle shot (FLASH) during breath holding.
      Intraarterial angiography was used as a reference. MR angiograms were evaluated
      for stenoses, length of renal arteries, accessory arteries, venous overlap, and
      image quality. RESULTS: The 3D TONE sequence was best for detection of severe
      stenoses (sensitivity, 100%; specificity, 89%), delineation of accessory
      arteries, and image quality. Overlap of renal veins was the most important
      disadvantage of 2D FLASH. Decreased saturation effects, however, can be
      advantageous in 2D TOF imaging. CONCLUSION: Use of the 3D TONE sequence provided
      improved image quality and diagnostic value compared with 3D FISP technique. The
      2D TOF sequence can be useful in combination with the 3D TONE sequence.

PMID- 7644628
TI  - Renal artery stenosis: evaluation of Doppler US after inhibition of angiotensin
      converting enzyme with captopril.
AB  - PURPOSE: To evaluate the modifications of Doppler ultrasound waveform morphology
      after inhibition of angiotensin-converting enzyme with captopril to increase the
      sensitivity of Doppler sonography in detecting renal artery stenosis. MATERIALS
      AND METHODS: Sixty-two renal arteries were studied in 31 hypertensive patients
      who underwent Doppler scanning before and 1 hour after administration of
      captopril prior to undergoing angiography. Pattern recognition criteria were
      applied to classify the Doppler waveforms as having a normal or pulsus tardus
      configuration. Doppler scanning results were compared with those of
      arteriography. RESULTS: On the basis of recognition of the pulsus tardus,
      precaptopril Doppler scanning showed 13 (68%) of 19 significant renal artery
      stenoses found at angiography (95% confidence interval, 0.43, 0.85), whereas 19
      (100%) of 19 stenoses were detected with postcaptopril Doppler scanning (95%
      confidence interval, 0.85, 1.0). CONCLUSION: Captopril significantly (95%
      confidence intervals) increases Doppler scanning sensitivity in detecting renal
      artery stenoses by inducing or enhancing the pulsus tardus distal to a
      significant renal artery stenosis.

PMID- 7644630
TI  - Dynamic contrast-enhanced subtraction MR angiography of the lower extremities:
      initial evaluation with a multisection two-dimensional time-of-flight sequence.
AB  - PURPOSE: To determine the clinical feasibility of a contrast material--enhanced
      two-dimensional (2D) magnetic resonance (MR) angiographic sequence in lower
      extremity arteries. MATERIALS AND METHODS: Four healthy volunteers and 12
      patients underwent dynamic contrast-enhanced MR angiography; all patients also
      underwent conventional angiography. A 2D multisection gradient-echo sequence with
      image subtraction was used for all MR imaging examinations. RESULTS: Oblique
      coronal contrast-enhanced MR angiography was completed in less than 4 minutes,
      with a 256 x 512 matrix. The arterial contrast enhancement ratio was 2.0 +/- 0.8
      (standard deviation), and the pre- and post-contrast contrast-to-noise ratios
      were 2.1 +/- 13.8 and 46.2 +/- 18.7, respectively. The sensitivity for MR
      angiography was 100% and specificity was 69% for distinction of vessels with
      greater than 50% stenoses from normal or mildly stenotic vessels. CONCLUSION:
      Dynamic contrast-enhanced 2D MR angiography is capable of increasing
      intraarterial signal intensity and depicting small vessel anatomy of the lower
      extremities over a large field of view in a short imaging time.

PMID- 7644631
TI  - Hand ischemia in patients with hemodialysis access grafts: angiographic diagnosis
      and treatment.
AB  - PURPOSE: To determine the cause of symptoms and efficacy of transcatheter therapy
      in a series of patients with dialysis grafts and hand pain referred for
      arteriography. MATERIALS AND METHODS: Thirteen patients with 14 hemodialysis
      grafts underwent arteriography for possible hand ischemia. The sites of proximal
      graft anastomosis were the distal radial artery (n = 6) and the mid- to distal
      brachial artery (n = 6). Transcatheter therapy was performed via the graft or by
      antegrade brachical puncture. RESULTS: The cause of symptoms was ischemia from
      obstructive arterial disease in seven cases (three with superimposed steal),
      graft steal alone in three, ischemic monomelic neuropathy in two, and carpal
      tunnel syndrome in two. Five arterial stenoses were treated with angioplasty,
      with improvement or resolution of symptoms in four patients. CONCLUSION: In this
      group, symptoms were usually the result of inflow or outflow arterial disease,
      alone or in combination with graft steal. Transcatheter therapy (angioplasty or
      embolization) is effective in selected cases.

PMID- 7644632
TI  - Artificial widening of the mediastinum to gain access for extrapleural biopsy:
      clinical results.
AB  - PURPOSE: To assess the utility of artificial widening of the extrapleural space
      to gain an extrapleural biopsy access route to the anterior and posterior
      mediastinum. MATERIALS AND METHODS: The authors retrospectively analyzed the
      findings in 20 patients who underwent biopsy of mediastinal masses after dilation
      of the extrapleural space with injection of approximately 20 mL of physiologic
      saline solution. The solution was injected to provide ventral (n = 6) or dorsal
      (n = 14) extrapleural access to the mediastinum. Biopsies were performed under
      computed tomographic guidance. RESULTS: Right-sided paravertebral extrapleural
      access to the mediastinum was achieved in 11 of the 14 patients in whom a dorsal
      approach was used. The paravertebral extrapleural soft tissue was dilated from a
      mean of 0.2 cm to a mean of 0.9 cm. Extrapleural biopsy was performed in nine
      patients. The pleura was traversed in four patients, causing pneumothoraces in
      two. A parasternal access route was created in all six patients in whom a ventral
      approach was used, and biopsies were performed without complications. The minimal
      width of the anterior mediastinum in these six patients increased from a mean of
      2.8 cm to a mean of 4.6 cm with dilation. CONCLUSION: Artificial widening of the
      extrapleural space provides an access route to the anterior and posterior
      mediastinum for large-bore biopsy.

PMID- 7644633
TI  - Coronary artery stenoses: three-dimensional imaging with electrocardiographically
      triggered, contrast agent-enhanced, electron-beam CT.
AB  - PURPOSE: To compare electron-beam computed tomography (CT) and coronary
      angiography for depiction of coronary artery stenoses. MATERIALS AND METHODS: In
      27 patients (age range, 50-70 years), electrocardiographically triggered axial
      electron-beam CT scans of the heart were obtained during breath hold and
      intravenous administration of contrast agent. Coronary arteries were
      reconstructed three-dimensionally. Electron-beam CT and angiographic results were
      compared. RESULTS: Significant enhancement within the vessel lumen (P < .001)
      permitted selective reconstruction of the inner coronary artery lumen. Nine of 11
      high-grade stenoses and all five occlusions in the proximal left anterior
      descending artery and three of five high-grade right coronary artery stenoses
      were clearly identified. Recognition of stenosis of the left circumflex artery
      was not reliable. Success after percutaneous transfemoral coronary angioplasty
      was documented in five of five patients by visualizing the increase in vessel
      diameter at repeat investigation. CONCLUSION: Contrast-enhanced electron-beam CT
      yields promising results concerning the visualization of coronary artery
      stenoses.

PMID- 7644634
TI  - Ovarian cancer recurrence: value of MR imaging.
AB  - PURPOSE: To assess magnetic resonance (MR) imaging in depiction of ovarian tumor
      recurrence and for identification of patients who may not benefit from surgical
      reexploration. MATERIALS AND METHODS: In a prospective study, 34 patients (mean
      age, 57.07 years) with surgically staged ovarian cancer underwent MR imaging
      before reexploration. Findings at MR imaging and surgery were correlated. MR
      imaging tumor depiction was correlated with tumor size, presence of ascites, and
      CA-125 levels. RESULTS: Tumor recurrence was identified in 29 patients at
      surgery. MR imaging depicted tumor in 20 patients. Accuracy for lesions smaller
      than 2 cm was 35% and increased to 82% for lesions larger than 2 cm (P < .01). MR
      imaging had low sensitivity for depiction of implants in the peritoneum and
      mesentery. Ascites improved depiction of smaller lesions (< 2 cm). MR imaging in
      combination with CA-125 levels improved detection of recurrent disease (CA-125
      measurement alone 53% vs CA-125 measurement and MR imaging 75%, P = .048).
      CONCLUSION: MR imaging is a useful adjunct to the clinical examination to
      identify patients with recurrent disease and those in whom reexploration may not
      be beneficial.

PMID- 7644635
TI  - Spontaneously changing gravid cervix: clinical implications and prognostic
      features.
AB  - PURPOSE: To assess the implications of spontaneous changes in the length and
      configuration of the gravid cervix during a single ultrasound (US) examination
      and to correlate specific cervical dimensions with pregnancy outcome. MATERIALS
      AND METHODS: Sonograms in 27 pregnant patients with a spontaneously changing
      cervix were studied prospectively. The length and width of cervical funneling and
      the length of intact cervix caudal to the funneling were measured when the
      cervical dimensions were most normal and most abnormal. Sonographic measurements
      were correlated with clinical and delivery data. RESULTS: Twenty patients
      delivered preterm, although only six delivered within a week of the US
      examination. Wider funneling of the internal os and a shorter segment of intact
      cervix caudal to the funneling both correlated with an increased likelihood of
      preterm delivery. CONCLUSION: Most patients with a spontaneously changing cervix
      deliver preterm. Measurements obtained when the cervix appears most abnormal are
      most predictive of early delivery.

PMID- 7644636
TI  - Recurrent nasopharyngeal tumors: preliminary clinical results with interventional
      MR imaging--controlled laser-induced thermotherapy.
AB  - PURPOSE: To evaluate magnetic resonance (MR) imaging-controlled laser-induced
      thermotherapy (LITT) in the treatment of recurrent head and neck tumors.
      MATERIALS AND METHODS: Six patients with recurrent nasopharyngeal tumors
      (squamous cell carcinoma [n = 4], pleomorphic adenoma [n = 2]) underwent LITT
      with local anesthesia. A 7-F introducing sheath was inserted into the center of
      the tumor followed by a specially designed laser emitter. Therapy was monitored
      on-line with MR thermometry, and the amount of necrosis was estimated with
      dynamic and static contrast material-enhanced sequences. RESULTS: All procedures
      were well tolerated with use of local anesthesia, with no clinically relevant
      side effects. MR thermometry depicted up to 15-mm-diameter areas of less signal
      intensity near the laser tip. Coagulative necrosis was achieved in all patients
      (volume range, 4-28 cm3), and clinical symptoms were reduced in four. CONCLUSION:
      MR imaging-controlled LITT may be a safe, minimally invasive alternative in the
      treatment of recurrent head and neck tumors.

PMID- 7644637
TI  - Predictive value of MR imaging-dependent and non-MR imaging-dependent parameters
      for recurrence of laryngeal cancer after radiation therapy.
AB  - PURPOSE: To determine the predictive value of several clinical and radiologic
      parameters for recurrence of laryngeal cancer. MATERIALS AND METHODS: Eighty
      previously untreated patients underwent magnetic resonance (MR) imaging before
      radiation therapy with curative intent. Tumor volume was calculated from T1
      weighted MR images. Cartilage was considered invaded by pathologic tissue if it
      had intermediate signal intensity on T1-weighted spin-echo (SE) MR images and
      high signal intensity on T2-weighted SE MR images. The minimum follow-up was 2
      years. RESULTS: Parameters such as age, sex, histopathologic findings, and
      invasion of the vocal muscle or pre-epiglottic space were not significantly
      correlated with tumor recurrence. Logistic regression analysis showed three
      relevant contributors: cord mobility, as judged clinically, and tumor volume and,
      more significantly, cartilage invasion, as seen at MR imaging. CONCLUSION: For
      untreated laryngeal cancer, MR imaging findings of tumor volume and cartilage
      invasion allow better patient selection for either radiation therapy or surgery.
      MR imaging is mandatory for T staging of laryngeal cancer.

PMID- 7644638
TI  - Substantial head trauma: value of routine CT examination of the cervicocranium.
AB  - PURPOSE: To evaluate the usefulness of routine performance of computed tomography
      (CT) of the craniocervical junction in unconscious patients with substantial head
      injury. MATERIALS AND METHODS: In a prospective study, CT of the head and the
      cervicocranium was performed in 202 patients with substantial cranial trauma
      (Glasgow Coma Scale scores of 3-6). Plain radiography was performed in all
      patients. Radiographs and CT scans were then blindly interpreted. RESULTS: Twenty
      eight patients (13.9%) had C-1 or C-2 fractures; plain radiographs did not
      demonstrate cervical fractures in 11 of these patients. Nine patients (4.4%) had
      fractures of the occipital condyles; plain radiographs did not demonstrate
      occipital condyle fractures in eight of these patients. CONCLUSION: Because 5.4%
      of all patients had fractures of either C-1 or C-2 and 4.0% had occipital condyle
      fractures not seen at plain radiography, routine additional performance of CT of
      the craniocervical junction is useful in patients with substantial cranial
      trauma.

PMID- 7644639
TI  - Suture closure in the human chondrocranium: CT assessment.
AB  - PURPOSE: To chronicle the development of ossification centers, sutures, and
      synchondroses in the chondrocranium throughout childhood by using computed
      tomography (CT). MATERIALS AND METHODS: One hundred eighty-nine children (age
      range, newborn to 18 years; median age, 4.0 years) without skull base deformity
      were referred for cranial CT. The closure of 18 sutures and synchondroses was
      graded. RESULTS: In the occipital bone at birth, six components were identified.
      The Kerckring ossicle rapidly fused to the supraoccipital bone within the 1st
      month. At age 1-3 years, the posterior and anterior intraoccipital synchondroses
      began to fuse. The occipitomastoidal, petro-occipital, and spheno-occipital
      synchondroses remained partially open into the teenage years. In the sphenoid
      bone at birth, 13 ossification centers were identified; most assimilated into the
      sphenoidal body during the first 2 years. Pneumatization of the sphenoid sinus
      appeared at age 1-2 years and advanced posteriorly over the next 3-5 years.
      CONCLUSION: The complex process of skull base development is chronicled, which
      provides CT standards for judgment of the patterns and timing of sutural or
      synchondrosal closure.

PMID- 7644640
TI  - Postnatal development of the central skull base: normal variants.
AB  - PURPOSE: To illustrate the normal variants and developmental anomalies of the
      skull base on computed tomographic (CT) scans. MATERIALS AND METHODS: One hundred
      eighty-nine children (age range, newborn to 18 years; median age, 4.0 years)
      without skull base deformity were referred for cranial CT. Normal developmental
      variants in the sphenoid and occipital bones were characterized. RESULTS: Sixteen
      normal variants of central skull base development were identified including
      anterior foramen in the presphenoid, remnant of the craniopharyngeal canal in the
      anterior portion of the postsphenoid, rounded defects in the central sphenoid,
      clefts and fissures along the basiocciput and basisphenoid, basioticum variants,
      notochordal remnant in the midline of the basiocciput, and fusion variants of the
      Kerckring ossicle with the supraoccipital portion of the occipital bone.
      CONCLUSION: The location and CT appearance of the 16 variants and anomalies are
      related to the known embryologic origin of this region. Recognition of such
      variants may prove necessary in evaluation of patients with skeletal dysplasias
      and disorders of skull base development.

PMID- 7644642
TI  - Acute subarachnoid hemorrhage: MR imaging with fluid-attenuated inversion
      recovery pulse sequences.
AB  - PURPOSE: To evaluate the usefulness of fluid-attenuated inversion recovery
      (FLAIR) magnetic resonance (MR) imaging sequences in the detection of acute
      subarachnoid hemorrhage (SAH). MATERIALS AND METHODS: MR imaging with FLAIR
      sequences was performed with a 0.5-T superconducting unit in 20 patients (aged 30
      72 years) with acute SAH due to a ruptured aneurysm and in 27 control subjects
      (aged 32-72 years). FLAIR images were obtained 2 hours to 2 days after ictus.
      Findings were evaluated and compared with computed tomographic (CT) findings.
      RESULTS: In all patients, acute SAH was clearly demonstrated as an area with
      signal intensity that was high relative to that of the normal cerebrospinal fluid
      and surrounding brain parenchyma at FLAIR imaging. This sequence was especially
      useful in demonstration of acute SAH in the posterior fossa, which was difficult
      to show at CT because of beam-hardening artifacts. In a double-blind comparison,
      no FLAIR images acquired in control subjects were confused with those acquired in
      control subjects were confused with those acquired in patients. CONCLUSION: FLAIR
      sequences reliably provide diagnostic images in patients with acute SAH.

PMID- 7644641
TI  - Brain lesions in patients with multiple sclerosis: detection with echo-planar
      imaging.
AB  - PURPOSE: To evaluate the detection of brain lesions with echo-planar imaging
      relative to conventional spin-echo (SE) imaging. MATERIALS AND METHODS: In 17
      patients (three men, 14 women; mean age, 31 years) with multiple sclerosis, the
      following were compared: single-shot proton-density- and T2-weighted and thin
      section T2-weighted echo-planar, proton-density- and T2-weighted multishot echo
      planar, and conventional SE sequences. Quantitative and qualitative criteria as
      well as lesion detectability were evaluated. The proton-density-weighted SE
      sequence was used as the standard of reference. RESULTS: Multishot sequences were
      superior to single-shot sequences in image quality and lesion detectability. With
      the multishot proton-density-weighted sequence, 53 of 54 large lesions and 23 of
      30 small lesions were detected; with the single-shot proton-density-weighted
      sequence, 38 of 54 large lesions and five of 30 small lesions were detected.
      CONCLUSION: With multishot echo-planar sequences, detectability of large lesions
      is similar to that with conventional SE imaging. Susceptibility artifact is
      diminished in comparison to single-shot echo-planar sequences.

PMID- 7644643
TI  - Cranial osteomyelitis: diagnosis and follow-up with In-111 white blood cell and
      Tc-99m methylene diphosphonate bone SPECT, CT, and MR imaging.
AB  - PURPOSE: To assess the usefulness of indium-111 white blood cell and technetium
      99m methylene diphosphonate bone single photon emission computed tomography
      (SPECT), computed tomography (CT), and magnetic resonance (MR) imaging in cranial
      osteomyelitis. MATERIALS AND METHODS: Twenty-six cases (25 patients: 13 male, 12
      female; mean age, 55 years) of suspected osteomyelitis were evaluated. Sixteen
      were postoperative. Final diagnosis was established by means of bone culture in
      18 cases and clinical follow-up in eight. RESULTS: Of 35 CT scans, 10 were true
      positive (TP); three false-negative (FN); 13, true-negative (TN); one, false
      positive (FP); and eight, equivocal. Of 36 SPECT scans, 19 were TP; 13, TN; one,
      FP; one, FN; and two, equivocal. Of 11 MR images four were TP; five, TN; and two,
      FN. CONCLUSION: CT is best for differentiation between soft-tissue and bone
      infection. MR imaging is best for assessment of the calvaria and skull base.
      SPECT is best for assessment of altered bone and may be the best technique for
      follow-up.

PMID- 7644644
TI  - Symptomatic webs of the upper esophagus: treatment with fluoroscopically guided
      balloon dilation.
AB  - PURPOSE: To evaluate treatment of symptomatic esophageal webs with
      fluoroscopically guided balloon dilation. MATERIALS AND METHODS: Nine
      consecutively seen patients (women aged 46-87 years) with esophageal webs who
      reported dysphagia underwent the procedure. Webs were dilated with 20-mm-diameter
      angioplasty balloons for less than 3 minutes (total procedure time, approximately
      30 minutes). Results of treatment (relief of dysphagia) were assessed by
      evaluating the clinical charts of six of the nine patients and by means of
      telephone interviews in four. Three patients were lost to follow-up. RESULTS: For
      effective treatment, one balloon inflation was necessary in seven patients, two
      in one patient, and three in another patient during the same session. In two
      patients with two esophageal webs each, the strictures were treated
      simultaneously. There were no complications, and all patients reported immediate
      symptomatic relief. Six patients remained asymptomatic during follow-up of 3
      months to 6.8 years (mean, 2.6 years). CONCLUSION: Fluoroscopically guided
      balloon dilation is easy and highly effective in treating symptomatic esophageal
      webs.

PMID- 7644645
TI  - Vascular complications of pancreatic transplantation: MR evaluation.
AB  - PURPOSE: To determine the value of magnetic resonance (MR) angiography and MR
      imaging with dynamic gadopentetate dimeglumine-enhanced gradient-echo (Gd-GRE)
      sequences in detection of vascular complications of pancreatic transplantation.
      MATERIALS AND METHODS: Three radiologists evaluated findings of 32 MR
      examinations in 20 adult patients who underwent pancreatic transplantation. The
      images were obtained with a surface coil and T1-weighted and T2-weighted fast
      spin-echo sequences, Gd-GRE sequences, and MR angiography. Vascular abnormality
      was confirmed at surgery or biopsy, and vascular patency with clinical
      correlation. RESULTS: Absence of flow was found in six of 32 studies (19%): acute
      vascular thrombosis of the vascular pedicle and/or branch vessels in four studies
      (three patients) and chronic pancreatic rejection in two studies (one patient).
      Gd-GRE images helped identify infarction in two patients. The sensitivity of MR
      angiography for detection of acute vascular compromise was 100%, and the
      specificity was 93%. CONCLUSION: MR angiography and MR imaging with Gd-GRE
      sequences allow detection of vascular complications of pancreatic
      transplantation.

PMID- 7644646
TI  - US-guided liver biopsy: predicting the effect of interventional treatment of
      hepatocellular carcinoma.
AB  - PURPOSE: To analyze the results of ultrasound (US)-guided biopsy as a predictor
      of the outcome of interventional treatment of hepatocellular carcinoma (HCC).
      MATERIALS AND METHODS: US-guided biopsy was performed in 125 lesions in 102 high
      risk patients, before transcatheter arterial embolization (TAE) (82 lesions) or
      before percutaneous ethanol injection (PEI) therapy (25 lesions, including 14
      lesions previously treated with TAE). Pathologic results were correlated with
      treatment effects. RESULTS: Results of biopsy confirmed 107 HCCs, which were
      classified as early (n = 17), frank (n = 67), sclerosing (n = 12), or poorly
      differentiated or undifferentiated (n = 11). Hypervascularity was observed in
      most frank HCCs, with a good response to TAE. Tumor vascularity in early or
      sclerosing HCCs was slight and did not respond to TAE. Sclerosing and poorly
      differentiated or undifferentiated HCCs enlarged after treatment, whereas early
      HCCs did not. Early HCCs were treated successfully with PEI therapy; sclerosing
      HCCs responded poorly to PEI therapy. CONCLUSION: Evaluation of histologic
      subtype of HCC by means of US-guided biopsy is essential, because subtype may
      affect treatment planning.

PMID- 7644647
TI  - Biliary cystadenoma and cystadenocarcinoma: clinical-imaging-pathologic
      correlations with emphasis on the importance of ovarian stroma.
AB  - PURPOSE: To evaluate cross-sectional imaging in the distinction of biliary
      cystadenoma from cystadenocarcinoma and in the determination of the presence of
      ovarian stroma. MATERIALS AND METHODS: In 34 patients, radiologic studies and
      specimen photographs and descriptions were reviewed retrospectively without
      knowledge of the patient group. Histologic features were reviewed without
      knowledge of the radiologic findings and analyzed for epithelial and stromal
      components. Correlation was made between the radiologic findings, gross
      morphologic features, internal fluid characteristics, and histologic features.
      RESULTS: The 34 patients had 27 biliary cystadenomas, 22 with ovarian stroma, and
      seven cystadenocarcinomas, four with ovarian stroma. Gross morphologic and
      imaging features suggestive of biliary cystadenocarcinoma included internal
      septation and nodularity. Septation without nodularity was seen only in biliary
      cystadenoma. Nonbilious fluid was the only feature associated with the presence
      of ovarian stroma but was not distinguishable on images. CONCLUSION: Imaging
      studies accurately reflect the nodularity and septation seen grossly to
      distinguish biliary cystadenoma and cystadenocarcinoma but do not allow
      distinction of the presence or absence of ovarian stroma.

PMID- 7644648
TI  - Development of a community mammography registry: experience in the breast
      screening program project.
AB  - PURPOSE: To assess the formation, implementation, and operation of a community
      mammography registry, which is a consolidated database for all mammography and
      breast biopsy reports within a community. MATERIALS AND METHODS: A registry was
      created in Lee County, Fla. Mammography interpretation data were provided by 13
      facilities and 38 radiologists organized in several private practice groups.
      RESULTS: The registry contains data on 87,926 mammograms and 3,234 breast
      biopsies performed between June 1991 and May 1994. The registry calculates
      individual and group mammography interpretation accuracy measures, such as
      sensitivity, specificity, positive predictive value, false-positive and false
      negative rates, and clinical outcome measures such as sizes and stages of
      malignant lesions detected. CONCLUSION: The registry allows community
      radiologists and mammography practices to compare their outcomes with those of
      their local peers and to published data and encourages focused interventions for
      quality improvement based on objective experience.

PMID- 7644649
TI  - Breast cancer: prediction with artificial neural network based on BI-RADS
      standardized lexicon.
AB  - PURPOSE: To determine if an artificial neural network (ANN) to categorize benign
      and malignant breast lesions can be standardized for use by all radiologists.
      MATERIALS AND METHODS: An ANN was constructed based on the standardized lexicon
      of the Breast Imaging Recording and Data System (BI-RADS) of the American College
      of Radiology. Eighteen inputs to the network included 10 BI-RADS lesion
      descriptors and eight input values from the patient's medical history. The
      network was trained and tested on 206 cases (133 benign, 73 malignant cases).
      Receiver operating characteristic curves for the network and radiologists were
      compared. RESULTS: At a specified output threshold, the ANN would have improved
      the positive predictive value (PPV) of biopsy from 35% to 61% with a relative
      sensitivity of 100%. At a fixed sensitivity of 95%, the specificity of the ANN
      (62%) was significantly greater than the specificity of radiologists (30%) (P <
      .01). CONCLUSION: The BI-RADS lexicon provides a standardized language between
      mammographers and an ANN that can improve the PPV of breast biopsy.

PMID- 7644650
TI  - Solitary pulmonary nodules: determining the likelihood of malignancy with neural
      network analysis.
AB  - PURPOSE: To test a neural network in differentiation of benign from malignant
      solitary pulmonary nodules. MATERIALS AND METHODS: Neural networks were trained
      and tested on the characteristics of 318 nodules. Predictive accuracy of the
      network was judged for calibration and discrimination. Network results were
      compared with those with a simpler Bayesian method. RESULTS: The Brier score was
      0.142 (calibration, 0.003; discrimination, 0.139) for the neural network and
      0.133 for the Bayesian analysis (calibration, 0.012; discrimination, 0.121).
      Analysis of the calibration curve revealed no significant difference (P < .05)
      between the slope (b = 1.09) and the line of identity (b = 1) for the neural
      network or the Bayesian analysis. The area under the receiver operating
      characteristic curve was 0.871 for the neural network and 0.894 for the Bayesian
      analysis (P < .05). There were 23 and 21 false-positive predictions and 18 and
      six false-negative predictions for the neural network and Bayesian analysis,
      respectively. CONCLUSION: The Bayesian method was better than the neural network
      in prediction of probability of malignancy in solitary pulmonary nodules.

PMID- 7644651
TI  - Benign noninflammatory bronchial stenosis: treatment with balloon dilation.
AB  - PURPOSE: To assess the efficacy of balloon dilation in the treatment of acquired,
      noninflammatory bronchial stenosis of benign origin. MATERIALS AND METHODS:
      Balloon bronchoplasty was performed with fluoroscopic guidance 36 times in 19
      bronchial stenoses in 16 consecutive patients, with use of a local anesthetic.
      RESULTS: Initial technical success was attained in all cases; clinical success
      was achieved in 13 (68%) of 19 bronchial stenoses. Six of the 19 stenoses were
      dilated unsuccessfully because they were caused by localized bronchomalacias. Of
      these initial successes, seven stenoses recurred but were redilated with success
      in four cases. At a mean follow-up of 21.6 months (range, 7-60 months),
      improvement in both fiberoptic bronchoscopy and respiratory status was seen in
      nine (69%) of 13 patients with fibrous stenoses. CONCLUSION: Balloon bronchial
      dilation can be proposed as the primary treatment in acquired, noninflammatory
      bronchial stenoses of various benign origins including stenoses after lung
      transplantation.

PMID- 7644652
TI  - Discrete lung involvement in systemic lupus erythematosus: CT assessment.
AB  - PURPOSE: To study the computed tomographic (CT) appearance of early lung
      involvement in systemic lupus erythematosus (SLE). MATERIALS AND METHODS: In a
      prospective study, 48 patients with serologically confirmed SLE but no prior
      clinical evidence of lung involvement underwent chest radiography, CT, and lung
      function tests. Radiographs and CT scans were compared, and CT scans were
      evaluated for signs suggestive of parenchymal and pleural disease. Extent and
      distribution of disease were determined. CT findings were correlated with
      clinical and functional data. RESULTS: Of 45 patients with normal chest
      radiographs, 17 (38%) had abnormal CT findings. Extent of disease was
      statistically significantly correlated with duration of clinical history (r =
      .93) and decreased single-breath diffusing capacity for carbon monoxide (r = .8)
      and ratio of forced expiratory volume in 1 second to forced vital capacity (r =
      .77). CONCLUSION: CT is superior to chest radiography for detection of
      functionally relevant pulmonary disease and is an important adjunct in early
      assessment of SLE.

PMID- 7644653
TI  - Automatic patient-instruction devices in thin-section CT of the thorax: impact on
      image quality.
AB  - PURPOSE: To determine what influence automatic patient-instruction (API) devices
      have on image quality of chest computed tomographic (CT) scans and whether the
      qualitative outcome justifies their routine use. MATERIALS AND METHODS: Thin
      collimation CT scans of two age- and sex-matched groups of 64 patients each were
      evaluated prospectively for the presence of breathing artifacts and for
      concomitant deterioration of image quality. Breathing commands in group 1 were
      given with the API device and in group 2 with technologist-performed patient
      instruction. Cardiac motion artifacts were not evaluated. The frequency of scans
      repeated owing to breathing artifact was determined. RESULTS: Image quality was
      worse in group 1 compared with that of group 2. The percentage of scans repeated
      was higher with API (38%) than without API (16%). CONCLUSION: API devices cannot
      be recommended for thin-section CT of the thorax. The large number of scans that
      must be repeated leads to a considerable increase in patient irradiation,
      scanning time, and cost.

PMID- 7644654
TI  - Filter wheel equalization in chest radiography: demonstration with a prototype
      system.
AB  - PURPOSE: To determine the feasibility of using the filter wheel equalization
      (FWE) technique for radiographic equalization in chest radiography. MATERIALS AND
      METHODS: An FWE system with two rotating wheels (one for each lung) with 25 lung
      shaped, 1.0-mm-thick copper templates was constructed. Preexposure images were
      acquired; the computer used these images to select and position templates for
      each lung. An equalized radiograph was then produced. Radiographs were acquired
      in two male volunteers (both 33 years of age) and in a phantom. RESULTS: Optical
      densities in the lungs and nonlung areas on a conventional phantom radiograph
      were 2.07 and 0.55, respectively; after equalization, the corresponding optical
      densities were 2.06 and 1.42. Outside the lungs, radiographic contrast
      (difference in optical density) increased threefold; in the lungs, there was a
      very small decrease in radiographic contrast due to beam hardening. Well
      equalized and relatively artifact-free radiographs were obtained with a 20-msec
      exposure time. CONCLUSION: The FWE system was shown in the laboratory to be
      feasible.

PMID- 7644655
TI  - Use of Tl-201 to detect untreated pediatric Hodgkin disease.
AB  - PURPOSE: To evaluate the usefulness of thallium-201 scintigrams in depiction of
      supradiaphragmatic lymphadenopathy associated with newly diagnosed Hodgkin
      disease in pediatric patients. MATERIALS AND METHODS: Thallium-201 and gallium-67
      scans of the chest and neck were obtained in 33 consecutive patients.
      Mediastinal, cervical, supraclavicular, and axillary lymph node activity was
      evaluated by independent raters, and results were compared in a blinded fashion
      with those on chest computed tomographic (CT) scans. RESULTS: Gallium and
      thallium scans demonstrated similar accuracy in depiction of CT-defined
      mediastinal masses. The kappa statistic indicated moderate to strong agreement
      with CT results. Similarly, there was no statistically significant difference
      between the accuracy of thallium and gallium scans in depiction of
      extramediastinal lymphadenopathy. CONCLUSION: Thallium scintigraphy is effective
      for depiction of lymphadenopathy in pediatric patients with untreated Hodgkin
      disease. Serial thallium studies may provide an alternative to gallium scans in
      monitoring response to treatment.

PMID- 7644656
TI  - Graves ophthalmopathy: MR evaluation of 10-Gy versus 24-Gy irradiation combined
      with systemic corticosteroids.
AB  - PURPOSE: To establish the most effective radiation dose for treatment of Graves
      ophthalmopathy (GO). MATERIALS AND METHODS: A combination of 10 Gy (n = 15) or 24
      Gy (n = 16) of radiation and corticosteroids was used to treat 31 patients with
      GO. Magnetic resonance (MR) images obtained before treatment showed swollen
      extraocular muscles with prolonged T2 relaxation times in all patients. RESULTS:
      Before therapy, T2 relaxation time of extraocular muscle was 79.6 msec (95%
      confidence interval, 76.3, 82.9) in the 24-Gy group and 77.4 msec (95% confidence
      interval, 74.6, 80.1) in the 10-Gy group (P = .32). After therapy, T2 relaxation
      time was 62.8 msec (95% confidence interval, 61.2, 64.4) in the 24-Gy group and
      68.9 msec (95% confidence interval, 66.8, 71.1) in the 10-Gy group. In the 24-Gy
      group, there was a significant decrease in T2 relaxation times (P = .001) and
      clinical response to initial treatment was better. At 1- and 3-month follow-up,
      the resistance rate was lower in the 24-Gy group. CONCLUSION: In treatment of GO,
      24 Gy of radiation is a more effective dose than 10 Gy when combined with
      systemic corticosteroids.

PMID- 7644658
TI  - Biliary tract: three-dimensional helical CT without cholangiographic contrast
      material.
AB  - Bile duct anatomy depicted with a three-dimensional (3D) model developed with
      helical computed tomography (CT) data was compared with cholangiographic
      depiction. The ductal system was completely displayed from all angles in four of
      six patients, as well as the stricture and length of bile duct between strictures
      and the bifurcation in five of six cases. 3D rendering can depict preoperative
      ductal anatomy.

PMID- 7644657
TI  - Interosseous ligaments: device for applying stress in wrist MR imaging.
AB  - To improve visibility of the interosseous ligaments at magnetic resonance (MR)
      imaging of the wrist, the authors made and tested a device to apply ulnar and
      radial stress. In two men with small lunotriquetral (n = 1) and scapholunate (n =
      1) ligament defects, depiction became evident only with stress deviation. Stress
      testing with this device increased the diagnostic accuracy of MR imaging for
      detection of these lesions.

PMID- 7644659
TI  - Portal vein: US-guided localization prior to transjugular intrahepatic
      portosystemic shunt placement.
AB  - To mark the portal vein prior to transjugular intrahepatic portosystemic shunt
      (TIPS) placement, metallic coils adjacent to (n = 18) and a wire within (n = 18)
      the portal vein were placed with ultrasonographic (US) guidance. The mean number
      of punctures for successful portal vein entry was 3.0 with coils and 2.9 with a
      wire, and the mean total procedure time was 127.5 and 110.0 minutes, respectively
      (differences, not significant), and mean time at US was 20 and 10 minutes,
      respectively.

PMID- 7644660
TI  - Lower extremities: MR angiography with a unilateral telescopic phased-array coil.
AB  - In a comparison of conventional and magnetic resonance (MR) angiography of the
      lower extremities, MR imaging was performed with extremity and body coils and a
      unilateral six-coil telescopic phased-array coil. In one of seven volunteers,
      average signal-to-noise ratio was 140% higher with the latter (p < .01), only
      three of five stations were necessary, and examination time was decreased 50%. In
      the four patients, correlation in findings was 100%.

PMID- 7644661
TI  - Firearms in the MR environment.

PMID- 7644662
TI  - Management of the breast specimen.

PMID- 7644663
TI  - Epinephrine administration for severe adverse reactions to contrast agents.

PMID- 7644665
TI  - Non-steroidal menses-regulating agents: the present status.

PMID- 7644666
TI  - Developments in anticonvulsants.

PMID- 7644664
TI  - Newer antifolates in cancer therapy.

PMID- 7644667
TI  - Developments in histamine H1-receptor agonists.

PMID- 7644668
TI  - Antifungal chemotherapy.

PMID- 7644669
TI  - Heterocyclic diversity: the road to biological activity.

PMID- 7644670
TI  - [Artistic dream reconstructions of the Wolf Man in the light of experimental
      findings].
AB  - The authors take the famous dream picture by the "wolf-man" as the starting-point
      for experimental research of their own and relate the one to the other. They see
      the significance of pictorial representations of dreams less in the supplementary
      information they convey about the "text" of dreams than in the fact that they
      give separate expression to motility-based "gesture-associated" memories and
      ideas. These need to be distinguished from "language-associated" memories as
      there are dissociated modes of encoding experience underlying verbal and
      pictorial representation. The splitting of these modes into different part-codes
      is an important component of repression. In addition, the pictorial
      representation of dreams enables the patient to re-associate part-codes and thus
      achieve a "deferred" reconstruction and complementation of significant
      experiences. In the authors view, pictorial representation is favorable to the
      discovery of repressed material; it is as yet however impossible to say exactly
      what relationship there is between verbalized and pictorial representation in the
      context of analysis.

PMID- 7644672
TI  - [Dream sequences. On the psychodynamic aspects of the dramaturgy of dreams].
AB  - Unlike Freud with his emphasis on the defensive function of dreams, the author
      concentrates on the creative aspect and compares the sequencing of dreams with a
      quasi-dramaturgical "scenic" organization of experience displaying notable
      analogies to a theatrical "production". Mentzos proceeds from two working
      hypotheses: dream sequences are not random but organized, in the sense that they
      reflect the succession of different life-stages or the presence of conflicting
      tendencies within the dreamer's mind; hence the order of the various sequence
      mirrors the "staging" of the various conflicts and the various attempts made to
      resolve them. The author attempts to substantiate this hypothesis with reference
      to a number of dreams and dream sequences.

PMID- 7644671
TI  - [The termination dream. On the significance of last dreams in psychoanalysis].
AB  - In the main, recent psychoanalytic literature on dreams proceeds on the
      assumption a) that the final dream in a course of psychoanalytic treatment
      directly reflects concrete themes associated with termination; b) that it
      reproduces, albeit in a strongly modified form, central themes from the initial
      stages; c) that initial symptomatologies recur; and d) that the analyst appears
      in a close and overt relation to this modified symptomatology. With reference to
      three cases from her own practice the author contends that a typology of
      "concluding" dreams does not reflect the reality of treatment and its success or
      failure and that there is little justification for generalizing about such
      dreams. The analysis of dreams, she insists, will always differ in accordance
      with the individual case.

PMID- 7644673
TI  - [Hemolytic-uremic syndrome in children].

PMID- 7644675
TI  - [Mechanisms of erythropoiesis].

PMID- 7644676
TI  - [Anemia in kidney diseases].

PMID- 7644678
TI  - [Practical aspects of erythropoietin treatment--state of current knowledge].

PMID- 7644677
TI  - [Hemolytic anemias in kidney diseases].

PMID- 7644679
TI  - [Iron metabolism in patients treated with erythropoietin].

PMID- 7644674
TI  - [Structured abstracting of scientific medical publications].
AB  - Abstracts play an important role in medical literature as the carriers of
      synthetic information. Their significance grows as computerized data bases are in
      use in which whole information should comprise no more than 250 words. Critical
      appraisal the abstracts' standard resulted in a proposal for data presentation
      divided into significant parts (structured abstracts). The abstract of an
      original clinical trial should contain description of the objective, design,
      setting, patients, intervention, main outcome measures, results and conclusions.
      The abstract of the review article should provide information about the purpose,
      data identification, study selection, data extraction, results of data synthesis
      and conclusions. This form obliges the authors to precise, logical formulation
      draws out the essential aspects of the work, facilitates literature review, and
      critical appraisal.

PMID- 7644680
TI  - [Resistance to EPO. Hyperfunction of the parathyroid glands].

PMID- 7644681
TI  - [Resistance to rHuEPO].

PMID- 7644682
TI  - [Metabolic aspects of using erythropoietin].

PMID- 7644683
TI  - [Use of human recombinant erythropoietin (rHuEPO) for treatment of anemia in
      patients with chronic kidney failure who don't require additional dialysis
      therapy].

PMID- 7644684
TI  - [Hemostatic disorders in uremia].

PMID- 7644685
TI  - [Nephropathies in the course of plasma cell disorders].

PMID- 7644686
TI  - The future of clinical toxicology in Europe.

PMID- 7644687
TI  - The role of clinical toxicology in the evaluation of health problems connected
      with the influence of chemical compounds on the inhabitants of Krakow.

PMID- 7644689
TI  - The evaluation of the health state of the workers occupationally exposed to low
      concentration of carbon disulphide (CS2). Part one: General medical examination
      and laboratory tests.
AB  - Prospective clinical studies were undertaken in 114 healthy men aged from 19 to
      46 years (mean 26) occupationally exposed to CS2. The 62 men from the control
      group were undergoing examination in the same way before employment and after 5
      years. The mean wages of the air concentration of CS2 at working posts was from 0
      to 65 mg/m3. After 5 years of exposure no considerable differences were found in
      general medical examination with diastolic/systolic blood pressure measurement,
      resting ECG record and chest X ray examination. However in LAB test the lipid
      metabolism disturbances occurred. After 5 years the serum concentration of
      triglicerides and betalipoproteides of exposed workers were significantly higher
      than in the control group. The serum concentration of total cholesterol of both
      group was increased. The mentioned changes of lipid metabolism are the factors
      which indicate atherosclerotical changes in the man occupationally exposed to low
      concentration of CS2.

PMID- 7644688
TI  - The evaluation of the threat of acute chemical compound poisonings among the
      adult inhabitants of Krakow in the years 1983 and 1993.
AB  - The aim of this study is to compare the frequency, kind and structure of acute
      poisonings of the Krakow residents in years 1983 and 1993. The group of 2132
      people treated for acute poisonings in the year of 1983 consisted of 50.6% men
      and 49.4% women, in 1993 the group of 2311 patients consisted of 60.7% men and
      39.3% women. The group of 154 poisoned who died at the place of accident in 1983
      consisted of 89.6% men and 10.4% women, whereas in 1993 the group of 220 such
      cases included 83% men and 17% women. The overall coefficient of poisonings
      during the years compared was 36.2 for 1983 and 42.0 for 1993. The coefficient of
      poisonings in the years examined of 1983, 1993 were 39.4 and 50.4 for men, and
      respectively 33.4 and 28.0 for women. In 1983 the poisonings with drugs (40.6%)
      were most numerous, ethanol came second (25%). In 1993 the first place took
      ethanol (31.8%), the second drugs (31.3%). The number of poisonings with carbon
      monoxide increased from 9.87% in 1983 to 13.6% in 1993. The comparison of numbers
      concerning the mortality rate of the treated patients and of those who died at
      the place of accident prior to any treatment, shows a considerable growth in
      mortality rate in 1983 from 1.1% up to 7.8% and in 1993 from 0.8% to 9.4%. Such a
      significant growth in this mortality rate is influenced by poisoning with ethanol
      and carbon monoxide at the place of accident.

PMID- 7644690
TI  - The evaluation of the health state of the workers occupationally exposed to low
      concentration of carbon disulphide (CS2). Part two: The complex way of the
      examination of the central nervous system (CNS).
AB  - The results of evaluation of health state of CNS of 114 healthy workers
      occupationally exposed to CS2 were demonstrated. The concentration of CS2 in the
      air was 0-65 mg/m3. 62 people from the control group underwent an examination in
      the same way--before employment and after 5 years. Psychiatric examination,
      psychological organic tests (Bender, Graham Kendall, Benton) and EEG record were
      performed. The examination results were evaluated separately and together by
      means of arbitrary scale of pathological changes which constituted a complex
      evaluation of CNS. A considerable deterioration of CNS was stated which was
      reflection of pathological changes of a functional type. After 5 years this
      complex way of evaluation of CNS in exposed workers significantly more
      pathological changes was evidenced then ones in the control group. In 20 exposed
      men who obtained the worst results in the evaluation of CNS, the head computer
      tomography was performed. In 60% mentioned people cortical and/or subcortical
      atrophy was found, described in most people to be small. At the same time it is
      important to state that mentioned CNS examination enables an early evaluation of
      functional and morphological state of CNS in people who are occupationally
      exposed to low concentration of CS2.

PMID- 7644691
TI  - The assessment of the condition of the liver in patients chronically exposed to
      mercury compounds in the place of settlement.
AB  - Problems with the assessment of organ damage caused by toxic substances in places
      of residence have recently appeared with increasing frequency. In spite of this
      there have been so far no uniform, objective research methods which could allow
      their accurate evaluation. This is why the attempt has been made to assess
      morphological and functional condition of the liver in patients chronically
      exposed to mercury compounds in the place of settlement. The research group
      consisted of 62 patients exposed to metallic mercury at a yearly rate exceeding
      24 kg for average duration of 16 years. Patients with the liver or biliary tract
      diseases, symptoms of chronic circulatory insufficiency, Australia (HBs+) antigen
      carriers and alcoholics were excluded from the research group. The control group
      consisted of 29 males. AST and ALT activity, prothrombin level, bilirubin and
      protein concentration in blood serum were measured and scintigraphic and USG
      examinations of the liver were performed. Mercury concentrations were also
      established. Scintigraphic examination yielded an abnormal image of the liver in
      52% of the exposed patients. The differences in frequency and intensity of
      scintigraphic changes in comparison with the control group were of statistical
      significance. No pathological changes were found in USG examination.
      Significantly higher ALT activity and bilirubin concentration and significantly
      lower total protein concentration were found in the exposed group. The
      correlation between the intensity of scintigraphic changes and mercury
      concentration were noted. Liver scintigraphic examination combined with
      biochemical analysis allows an assessment of the liver condition in chronic
      exposure to mercury compounds in the place of settlement.

PMID- 7644692
TI  - Concentration of magnesium in hair of inhabitants of down-town Krakow, the
      protective zone of Steel-Mill "Huta im. Sendzimira" and Tokarnia village.
AB  - Concentration of magnesium in hair was measured by atomic absorption
      spectrophotometry in 3 groups of persons aged 48 to 79. All the participants of
      the study lived at least 10 years and none of them worked in industry or
      commerce. Their work place was in the distance less than 10 kilometers from their
      dwellings. The first group comprised inhabitants of the protective zone
      surrounding the Steel-Mill Huta im. Sendzimira, southern Poland, regarded as one
      of the biggest source of air, water and soil pollution. The second group
      constituted inhabitants of down-town Krakow (some 15 km from the steel-mill). The
      third group were the inhabitants of Tokarnia village with favourable
      microclimate. Though the concentration of magnesium in hair was similar to the
      one reported by other authors, it was shown that the concentration of this cation
      in hair was the smallest in the inhabitants of down-town Krakow and the highest
      in Tokarnia. The differences were statistically significant. It is postulated
      that magnesium hair concentration may be an easier, cheaper and less invasive
      indicator of body magnesium depletion.

PMID- 7644693
TI  - Progress in the CT evaluation of the cerebral atrophy in acute poisoning with
      carbon monoxide.
AB  - The aim of the study was to evaluate the frequency of occurrence and
      intensification of the cerebral atrophy changes taking into consideration the age
      of the examined, in the course of acute poisoning with carbon monoxide. A
      modified Messe's method was used to evaluate brain atrophy. 111 patients
      intoxicated with carbon monoxide were examined using CT of brain. In 75% of them
      cerebral atrophy was stated. To evaluate a dynamics of changes a control CT
      examination was performed in 72 patients after a year.

PMID- 7644694
TI  - Intermediate syndrome in acute fenitrothion poisoning.
AB  - Fenitrothion has been reported as one of the organophosphates causing so called
      "intermediate syndrome"--clinical entity of still unclear reasons. That is why we
      decided to perform a retrospective examination of oral intoxication with this
      compound. Clinical course of 16 cases were analysed. Clinical state on admission,
      AChE activity and pesticide concentration in blood were considered. Gastric
      lavage, atropine and oximes were included in the treatment. 6 patients died in
      the period of 5 to 22 days (mean 11.8) from poison intake. All 6 revealed slight
      signs of poisoning at the time of admission (first 24th). AChE was moderately
      inhibited. Patients' clinical state was deteriorating and AChE activity was
      decreasing during next 48 h even though oximes therapy was applied. Intubation
      and mechanical ventilation was required. Fenitrothion concentration in blood
      varied from 470 to 8350 ng/ml (mean 2823 ng/ml). In 3 fatal cases toxicological
      examination of autopsy tissue was done. High fenitrothion concentration was found
      in adipose tissue and also in the brain. In the group of 10 recovered patients
      "intermediate syndrome" was not observed in 3 only. AChE activity returned to
      normal quickly. Fenitrothion concentration ranged from 96 to 360 ng/ml (mean 202
      ng/ml). In the remaining 7 clinical state became worse during next 48-72 hours
      after temporary improvement. Respiratory failure and increasing AChE activity
      inhibition were major signs. Fenitrothion concentration varied from 180 to 3020
      ng/ml (mean 1690 ng/ml). AChE inhibition persisted even for 30 days from
      poisoning.

PMID- 7644695
TI  - Acute poisonings with drugs of abuse.
AB  - The drug overdose resulting in acute intoxication diagnosed in the 106 drug
      abusers in period form June to December 1994. The screening drugs identification
      was performed using immunoassays Triage and Vitalab Eclair manufactured by MERCK.
      Benzodiazepines followed by barbiturates and opiods were most often the cause of
      acute poisonings among the adult Krakow inhabitants. The results presented
      indicate that only adequate clinical observation, laboratory tests performance
      and establishing of intoxication state (acute poisoning, chronic intoxication or
      withdrawal) allows a complete patient evaluation.

PMID- 7644696
TI  - Thermoregulatory dysfunction secondary to acute ethanol poisoning.
AB  - Acute ethanol poisoning followed by drugs of abuse and psychiatric disorders is
      the most common cause of hypothermia. An attempt to evaluate the ethanol
      poisoning degree considering body temperature, serum osmolality, osmolal gap and
      ethanol concentration measurements was the aim of study. The lowest body
      temperature measured using infrared tympanic thermometer--First Temp Genius,
      Sherwood Medical was noted in the severely poisoned patients and was well
      correlated with the serum osmolality and with the osmolal gap.

PMID- 7644697
TI  - Development of toxicological information in the Department of Toxicology
      Collegium Medicum, Jagiellonian University.
AB  - The Poisons Information Centre at the Department of Toxicology gives
      toxicological information every day for full 24 hours. The information is based
      on the file of chemical compounds and substances. Each telephone enquiry is
      recorded and then analysed by the staff of Poisons Information Centre. The
      toxicological information covers children, adults and mass-poisonings cases, Most
      of the enquires concern consultation, then information and last consultation and
      information. During the regular telephone service most enquires are made about
      drug poisonings, ethanol, pesticides and mushrooms. Most of the enquiries are
      made by physicians. Private persons come next. Further activity of Poisons
      Information Centre depends on the access to the world literature and
      popularisation of toxicological knowledge among the people. This will contribute
      to higher rate toxicological enquires from private persons.

PMID- 7644698
TI  - Department of Toxicology in Krakow on the eve of its 30th anniversary.

PMID- 7644699
TI  - A new way to take temperature in clinical practice.

PMID- 7644700
TI  - Location and secretion of brain angiotensinogen.
AB  - Angiotensinogen is a glycoprotein with intriguing structural similarities to the
      serine proteinase inhibitors but with only one known function: to act as a
      substrate in the enzymatic generation of angiotensin peptides. It is expressed as
      a constitutive protein by the liver and various other tissues, including the
      brain. It is in this tissue that the expression of angiotensinogen attains its
      most complex and controversial manifestations. In late gestation, an unfolding of
      cellular expression occurs, starting at an epicentre in the eppendymal and
      astroglia cells of the hypothalamus, which rapidly and sequentially spreads to
      sub-cortical and then cortical regions, concentrating at sites of electrolyte,
      fluid and pressure regulation. This initial burgeoning of astroglial
      angiotensinogen is trailed by a wave of neuronal expression in various limbic and
      sensorimotor regions of the brain. The predominance of AT2 receptors in these
      regions suggests that the RAS actions are mediated by AT2 receptors. The
      angiotensinogen found in the CSF and secreted by cultures of glia and neurones is
      similar to the two major molecular sizes found in plasma. However, by
      electrophoretic separation on the basis of charge imparted by differential
      glycosylation, it can be shown that glia and neurones secrete distinct forms. The
      expression of different forms is under hormonal regulation. If these structural
      forms are shown to affect function, then the resulting ramifications may extend
      to pathological conditions, such as hypertension. Primary cell cultures of
      astrocytes secrete angiotensinogen constitutively and in a region-specific manner
      related to the size of the sub-population of secretory cells. Neurone cultures
      secrete angiotensinogen at about 25% the rate of hypothalamic astrocytes. The use
      of RT-PCR shows that both cell types express angiotensinogen mRNA. There is still
      an unresolved mismatch between these data and in situ hybridization
      histochemistry which shows expression limited to astrocytes but it is suggested
      that changes to more appropriate techniques will resolve any outstanding
      discrepancies.

PMID- 7644701
TI  - Tachykinin receptors in gastrointestinal motility.
AB  - For a long time research on the action of TKs on gastrointestinal tissue has been
      demonstrating the importance of the TKs as non-cholinergic stimulators of
      motility in most parts of the mammalian gastrointestinal tract. The past years
      witnessed the development of TK agonists and antagonists selective for the
      various receptor types, which prompted a wealth of new insight into the
      pharmacology and molecular biology of the TK receptors. This knowledge now allows
      a more specific elucidation of the role of TKs and their receptors in the various
      aspects of gastrointestinal motility, not only in normal tissue but also under
      pathological conditions.

PMID- 7644702
TI  - Primary structure of solitary form of gonadotropin-releasing hormone (GnRH) in
      cichlid pituitary; three forms of GnRH in brain of cichlid and pumpkinseed fish.
AB  - GnRH is a decapeptide family with at least nine distinct structures. Vertebrates,
      except for most placental mammals, have more than one of these GnRH forms within
      the brain. We report chromatographical and immunological evidence that three
      forms of GnRH are in the brains of both cichlid (Haplochromis burtoni) and
      pumpkinseed (Lepomis gibbosus) fishes. We argue that the three forms correspond
      to those previously described as sea bream GnRH (sbGnRH), chicken GnRH-II and
      salmon GnRH. In contrast, only one GnRH form was present in the pituitary of the
      cichlid and is identified as sbGnRH by amino acid sequence. This is the first
      report in which the primary structure of GnRH is determined from pituitary
      tissue. The N-terminus was identified by monitoring the digestion of the peptide
      by pyroglutamate aminopeptidase with matrix assisted laser desorption/ionization
      (MALDI) mass spectrometry (MS). The amidation of the C-terminus was established
      using an esterification procedure for monitoring with MALDI-MS. This report
      supports the idea that three forms of GnRH within one species is widespread in
      the order Perciformes. The present study establishes sbGnRH as the third GnRH
      form in H. burtoni and predicts that sbGnRH is synthesized in preoptic neurons,
      then transported to the pituitary in the preoptic-hypophyseal axons for the
      release of one or both gonadotropins.

PMID- 7644703
TI  - Generation of cyclic guanosine monophosphate in brain slices incubated with
      atrial or C-type natriuretic peptides: comparison of the amplitudes and cellular
      distribution of the responses.
AB  - Natriuretic peptides have been demonstrated to induce a variety of effects when
      administered into the brain. Most studies to date have tested the effects of
      'atrial' natriuretic peptide (ANP), but C-type natriuretic peptide (CNP) has
      recently been suggested to be the predominant form of natriuretic peptides within
      the brain. We therefore have compared the amplitudes of the cyclic guanosine
      monophosphate (cGMP) responses induced by either ANP or CNP in slices form
      different rat brain regions. Whereas both peptides induced the generation of
      cGMP, CNP-evoked responses were never greater than those obtained with ANP,
      regardless of the brain region used or the age of the animal. In diencephalon,
      ANP even induced a significantly higher cGMP response than CNP. To test which
      cells were targets to the actions of the peptides, brain slices were incubated
      with fluorocitrate (a drug that selectively blocks the metabolism of glial
      cells). Fluorocitrate totally blocked the ANP-evoked cGMP responses in brain
      slices. In contrast, fluorocitrate reduced only partially the responses evoked by
      sodium nitroprusside (a drug that stimulates soluble guanylate cyclase, which is
      contained predominantly in neurons). Likewise, the cGMP response induced by CNP
      was only partially affected by fluorocitrate. These results indicate that: (1)
      CNP is not more potent than ANP in terms of its ability to generate cGMP in rat
      brains; (2) brain cells generating cGMP upon exposure to ANP are predominantly
      glial; and (3) CNP-responsive cells are partly glial, but belong at least in part
      to a different compartment than ANP-responsive cells.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7644704
TI  - Neuropeptide Y is expressed in islet somatostatin cells of the hamster pancreas:
      a combined immunocytochemical and in situ hybridization study.
AB  - Neuropeptide Y (NPY) is known to occur in the autonomic nervous system, including
      the pancreatic islet innervation. We now present evidence that NPY is also
      expressed in endocrine islet cells in hamster pancreas. Thus, NPY
      immunoreactivity and gene expression were detected in peripheral islet cells,
      using immunocytochemistry (ICC), in situ hybridization (ISH), and a combination
      of these techniques. Double immunostaining for NPY and somatostatin enabled
      localisation of NPY ot the vast majority of the somatostatin cells. However, a
      few somatostatin cells were devoid of NPY immunoreactivity and an occasional NPY
      immunoreactive cell was devoid of somatostatin. ISH with an NPY mRNA specific
      probe, showed labelling of cells in the islet periphery. Furthermore, combined
      ISH for NPY mRNA and ICC for somatostatin showed autoradiographic labelling of
      somatostatin cells to a varying degree. Both somatostatin and NPY are inhibitors
      of insulin and/or glucagon secretion. Thus, in the islets these two peptides may
      be coreleased and cooperate in the regulation of islet hormone secretion. The
      role for NPY emanating from islet cells is probably paracrine rather than
      endocrine.

PMID- 7644705
TI  - Distribution of enkephalin immunoreactivity in sympathetic prevertebral ganglia
      and digestive tract of guinea-pigs and rats.
AB  - The aim of the present study was to determine the distribution of methionine
      enkephalin (ME) and leucine-enkephalin (LE) immunoreactivity in the sympathetic
      prevertebral ganglia (coeliac plexus and inferior mesenteric ganglion) and in the
      myenteric plexus-muscular layer complex of the digestive tract in guinea-pigs and
      rats. This study was performed using the same immunological approaches including
      radioimmunoassays and HPLC characterization as those used previously on cats in
      order to be able to make inter-region and inter-species comparisons. In rat and
      guinea-pig prevertebral ganglia, the distributions of the enkephalin
      immunoreactivities were comparable and were characterized by a low ME/LE
      concentration ratio, of less than 1. In the digestive tract of rats, the
      enkephalin immunoreactivities were homogeneously distributed, whereas in guinea
      pigs, they were found to be very low in the lower oesophageal sphincter and high
      in the duodenum. In both species, the ME/LE concentration ratio was around 2. The
      ME/LE concentration ratio determined in the present study in peripheral nervous
      structures was much lower than that determined previously in the rat brain.
      Radioimmunoassay and biochemical data might indicate that different mechanisms
      are responsible for the processing and/or degradation of enkephalins in the
      central and peripheral nervous systems. The present study provides further
      evidences that there are tissue- and species-dependent differences in the
      distribution of enkephalin immunoreactivities. These differences should be taken
      into consideration when dealing with the effects and the role of enkephalins in
      the nervous control of intestinal motility in mammals.

PMID- 7644706
TI  - Electronic surveillance of the pharmacology-toxicology literature.

PMID- 7644707
TI  - Electronic surveillance of the pharmacology-toxicology literature: the need for
      controlled vocabularies and registry systems.
AB  - Controlled vocabularies of "preferred names" and registry systems are essential
      in electronic indexing, storing, searching, and retrieving the world's published
      literature. The most efficient and comprehensive search is accomplished by using
      the preferred name. Without a controlled vocabulary or a registry system, it
      would be necessary to remember every name that might have been used by authors
      since January 1966, in order to retrieve all the citations on a chemical from
      over 7.8 million citations currently in the National Library of Medicine's
      MEDLINE and its backfiles. The task of creating the list of subject descriptors
      that make possible the surveillance of published literature via electronic
      databases requires the participation of the scientific community in developing
      domain-specific nomenclature, drug classification, controlled vocabularies, and
      registry systems as well. The biological unions of the International Council of
      Scientific Unions and its Committee on Data for Science and Technology are major
      contributors to the establishment and dissemination of standards for biological
      terminology and nomenclature. The objectives of the IUPHAR Nomenclature Committee
      include the development of a rational framework for the nomenclature of receptor
      classes or families and a classification for therapeutic agents. This will help
      define rules for the characterization and classification of receptors that are
      stable and easy to comprehend. The International Union of Pharmacology publishes
      guidelines for the classification of drugs and the nomenclature of receptors and
      ion channels.

PMID- 7644708
TI  - Talc: Consumer Uses and Health Perspectives. Proceedings of a workshop. Bethesda,
      Maryland, January 31-February 1, 1994.

PMID- 7644709
TI  - Talc: occurrence, characterization, and consumer applications.
AB  - Talc is a mineral compound with unique attributes and significant commercial
      importance. As used in consumer products, talc has a long and proven history of
      safe use. Direct consumer applications include body powders, other cosmetic
      formulations, pharmaceutical tableting, and some confectionery food products.
      Production, characterization, and consumer applications of FDA-regulated talc
      products, particularly cosmetics, are described. The implementation of stringent
      safety and quality control measures designed to ensure the absence of asbestos
      fibers from consumer talc products is discussed. Consumer exposure to talc
      containing products is at least 350 times lower than permissible industrial
      exposure.

PMID- 7644710
TI  - The regulatory status of talc.

PMID- 7644711
TI  - The NTP talc inhalation study: a critical appraisal focused on lung particle
      overload.
AB  - Recently published results in a NTP report of a 2-year inhalation study with talc
      in rats and mice seem to fit the category of being associated with particle
      overload quite well: Exposure concentrations of 6 and 18 mg/m3 induced pulmonary
      inflammation and fibrosis in male and female rats and induction of lung tumors
      (in female rats only) of the high exposure group; mice of either sex showed an
      inflammatory response but did not show pulmonary fibrosis or lung tumors.
      Analysis of the particle accumulation kinetics in lungs of both rats and mice
      indeed shows that lung overload had been reached at both exposure concentrations
      in both species resulting in increased talc accumulation of high lung burdens.
      This and the chronic inflammatory response indicate that the maximum tolerated
      dose (MTD) had been exceeded at both exposure levels. This result was predictable
      based on the outcome of a 4-week range-finding study prior to initiation of the
      chronic talc study; however, the short duration of the range-finding study may
      have been inadequate to give great confidence in the prediction and therefore may
      have accounted for the failure to include a concentration below the MTD in the
      chronic study. Further analysis of the results of the chronic talc study show
      that talc particles behave like other low-toxicity particles such as TiO2 and
      toner with respect to effects on lung clearance and chronic pulmonary
      inflammation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7644712
TI  - The lack of an ovarian effect of lifetime talc exposure in F344/N rats and B6C3F1
      mice.

PMID- 7644713
TI  - An analysis of the National Toxicology Program's (NTP) Technical Report (NTP TR
      421) on the toxicology and carcinogenesis studies of talc.
AB  - The NTP toxicology and carcinogenicity studies of nonasbestiform, cosmetic-grade
      talc (the NTP Talc Report) were conducted by exposing male and female F344/N rats
      and B6C3F1 mice to target aerosol concentrations of 0, 6, and 18 mg/m3 talc for 6
      hr daily, 5 days per week. Based on results of the high dose, the Report
      concluded that talc caused lung tumors in female rats and pheochromocytomas in
      male and female rats, and there was no evidence of carcinogenic activity in mice.
      A thorough evaluation of lung toxicity revealed that talc-induced lung tumors
      occurred only in the group of animals that exhibited the most profound degree of
      chronic toxicity. However, these data were presented as empirical observations
      rather than discussed in a manner that would relate them to the risk assessment
      implications of the bioassay, i.e., relevant data were collected but not "used."
      In addition, the evaluation of the pheochromocytomas was inadequate because it
      failed to place sufficient emphasis on the spontaneous incidence of this tumor in
      rats. These deficiencies caused the author to vote against the conclusions
      presented in the Talc Report when it was reviewed by the NTP Board of Scientific
      Counselors. The appropriate conclusions are (1) the data do not indicate that the
      pheochromocytomas were treatment-related; (2) the maximum tolerated dose (MTD)
      was exceeded in the female rats exposed to the high dose; and (3) talc is not
      expected to cause lung tumors under conditions of exposure that fail to result in
      marked chronic lung toxicity.

PMID- 7644714
TI  - The relevance of rodent tumors in assessing carcinogenicity in human beings.

PMID- 7644715
TI  - A review of perineal talc exposure and risk of ovarian cancer.
AB  - The authors provide a detailed review of the events that led to the interest in
      talc as a possible ovarian carcinogen, the epidemiological studies published to
      date, and their perspective on the interpretation of the findings including
      potential limitations, biases, and issues surrounding the plausibility of a
      causal association. The authors conclude that the range of relative risk
      estimates from epidemiology, 1.0 to 1.8, is plausible, but that additional
      epidemiologic studies, especially prospective investigations are needed. In
      addition, clinicopathological studies are needed to confirm or deny the reports
      of talc embedded in human ovarian tissue and reports of talc migration through
      the human female reproductive tract.

PMID- 7644716
TI  - Application of the benchmark method to risk assessment of trichloroethene.
AB  - An alternative approach for risk assessment of nongenotoxic substances, the
      benchmark method, has been evaluated and applied to trichloroethene as a test
      case. The benchmark dose is the dose that corresponds to a specific increase in
      risk, normally 1 or 10%. Experimental data from the literature on trichloroethene
      were used for these calculations. Eighty sets of data on effects on liver,
      kidney, the central nervous system, and tumors were analyzed. All non-observed
      effect levels (NOELs) were higher than the benchmark dose corresponding to 1%
      extra risk, and 42% of the NOELs and 93% of the lowest-observed-effect levels
      (LOELs) were higher than the benchmark dose corresponding to 10% extra risk. The
      present study confirms that the benchmark methodology gives a more detailed
      picture of dose-response relationships than risk assessment using the NOEL/LOEL
      approach and facilitates comparison between various toxicity studies. However,
      the polynomial regression models used in the present study quite often failed to
      fit the experimental data. Despite the advantages with the benchmark approach,
      several factors must be considered in the risk assessment process. In the case of
      trichloroethene, a revised risk assessment using the benchmark approach would
      lead to a similar guideline value as the traditional NOEL/LOEL approach.

PMID- 7644717
TI  - Challenges to default assumptions stimulate comprehensive realism as a new tier
      in quantitative cancer risk assessment.
AB  - The current practice in carcinogen risk assessment of using a linearized
      multistage model and assuming low-dose linearity is based on several false
      premises. In many cases linearity at low doses would not be expected based on the
      interaction between the multiple components in the carcinogenic process. The two
      stage growth models, involving multiple mutations and cell birth and death rates,
      provide one means of exploring these interactions. In addition, if carcinogenesis
      is considered to be the imbalance between invading substances and defense
      mechanisms, then the cancer probability depends on how much the substance
      increases or decrease the number of defenders or their efficiency as well as
      increasing or decreasing the number of invaders. Challenges to low-dose linearity
      and other default assumptions have stimulated the development of new risk
      assessment methodologies as have the need for more realistic estimates of risk,
      better uncertainty characterization, and greater utilization of cost-benefit
      analyses, and other tools for risk management decision making. "Comprehensive
      realism" is an emerging quantitative weight-of-evidence risk assessment
      methodology which is designed to reflect all of the relevant and available
      information and the current state of knowledge about the health risks associated
      with a substance.

PMID- 7644718
TI  - Environmental tobacco smoke and coronary heart syndromes: absence of an
      association.
AB  - Concerns about possible cardiovascular and especially coronary effects of
      environmental tobacco smoke (ETS) derive from the reported effects of active
      smoking. Despite similarities, however, ETS has composition and physical
      characteristics different from the mainstream smoke (MS) that active smokers
      inhale and appears relatively more chemically inert and less biologically active.
      ETS doses to nonsmokers are small and often below the sensitivity of detection
      technologies. They are several orders of magnitude less than MS doses in active
      smokers. Numerous epidemiologic studies report that the active smoking of less
      than 10 cigarettes/day is not associated with measurable risk of coronary heart
      disease (CHD). Thus, even assuming that ETS and MS have equivalent biologic
      activities, conceivable ETS doses to nonsmokers are far below apparent no-effect
      thresholds for active smoking. Hence, it is no surprise that epidemiologic
      reports are inconclusive about a possible association of ETS exposure and CHD,
      some suggesting a slight elevation, others a reduction of risk. Often, the
      elevations reported are higher than the CHD risk values associated with active
      smoking. Such equivocations likely result from the presence of contrasting
      protective or aggravating confounders, of which more than 200 have been reported
      in the literature--confounders that were not and could not be adequately
      controlled by any epidemiologic study. By scientific standards, the weight of
      evidence continues to falsify the hypothesis that ETS exposure might be a CHD
      risk factor.

PMID- 7644719
TI  - Benchmark Dose Workshop: criteria for use of a benchmark dose to estimate a
      reference dose.
AB  - The purpose of the Benchmark Dose Workshop was to assess the feasibility and
      implications of replacing the no observed adverse effect level (NOAEL) with a
      benchmark dose (BMD) when deriving reference doses and concentrations (RfDs and
      RfCs). The workshop participants supported the use of the BMD method to remove
      many of the limitations inherent in using the NOAEL approach. Participants
      endorsed in general the use of a BMD for all quantal noncancer health effects and
      endorsed in particular the BMD for assessing developmental toxicity based on data
      presented at the workshop. The discussions of implementation recognized the need
      to demonstrate that changing from a NOAEL to a BMD gives the risk manager more
      certain information on which to base decisions. Most participants agreed that the
      current NOAEL-derived RfDs and RfCs are sufficiently protective and should only
      be changed as data become available for estimating a BMD. It was recognized that
      to achieve general acceptance of the BMD approach, it will have to be applied to
      a variety of endpoints.

PMID- 7644720
TI  - Cell-type-specific leukemia analyses in a combined cohort of more than 208,000
      petroleum workers in the United States and the United Kingdom, 1937-1989.
AB  - A large number of epidemiologic studies of workers in the petroleum industry have
      been conducted to investigate the carcinogenic and other health effects of
      exposure to petroleum products during manufacture and distribution. Of particular
      interest is the relationship between exposure to benzene or benzene-containing
      liquids in the petroleum industry and leukemia risk. However, few studies have
      investigated cell-type-specific leukemia risk. In the present investigation, all
      cohort studies of petroleum workers in the United States and the United Kingdom
      were combined into a single database for cell-type-specific leukemia analysis.
      The majority of these workers were petroleum refinery employees, but production,
      pipeline, and distribution workers in the petroleum industry were also included.
      The combined cohort consisted of 208,741 petroleum workers. Between 1937 and
      1989, these workers contributed a total of 4,665,361 person-years of observation.
      More than 56 thousand deaths were reported among these workers during the 53
      years of observation. Cell-type-specific leukemia risks were calculated using a
      meta-analysis procedure appropriate for combining occupational cohort studies.
      These risks were expressed in terms of cell-type-specific leukemia standardized
      mortality ratios (meta-SMRs). The meta-SMR for acute myelogenous leukemia was
      0.96. The lack of an increase of acute myelogenous leukemia was attributed to the
      low levels of benzene exposure in the petroleum industry, particularly in
      comparison to benzene exposure levels in some previous studies of workers in
      other industries, who had been found to experience increased risk of acute
      myelogenous leukemia. Similarly, no increase in chronic myelogenous, acute
      lymphocytic, or chronic lymphocytic leukemias was found in petroleum workers
      (meta-SMRs of 0.89, 1.16, and 0.84, respectively). Meta-analyses restricted to
      refinery studies or to studies with at least 15 years of follow-up yielded
      similar results. The findings of the present investigation are consistent with
      those from several recent case-control studies.

PMID- 7644721
TI  - ISRTP Council comments regarding "a public health and regulatory perspective on
      risk of dioxin-like compounds". Submitted on behalf of ISRTP Council.

PMID- 7644722
TI  - The International Society of Regulatory Toxicology and Pharmacology International
      Achievement Award.

PMID- 7644723
TI  - [Pancreatic duct system: radiologic anatomy, anatomical variations, and general
      principles of pancreatographic semiology].

PMID- 7644724
TI  - [Diagnostic imaging of idiopathic synovial osteochondromatosis].
AB  - To study the characteristic diagnostic imaging features of idiopathic synovial
      osteochondromatosis with different imaging techniques as well as the differential
      diagnosis between idiopathic and secondary forms, 7 patients with idiopathic
      synovial osteochondromatosis were retrospectively examined from January, 1988,
      through December, 1993. In 6 patients the disease was monoarticular (the shoulder
      in 4 patients, the elbow in one patient and the hip in another one). In one
      patient two joints were involved--i.e., the left elbow and the right knee. In all
      cases the clinical picture was characterized by pain and functional impairment of
      the involved joint, which was swollen in 3 patients. The definitive diagnosis was
      made on the basis of surgical and/or arthroscopic findings in 4 cases and of
      radiologic and MR findings in 4 cases and of radiologic and MR findings in 4
      cases. In all patients conventional radiology showed multiple juxtaarticular
      calcified and/or ossified bodies, mostly uniform in size. Calcification patterns
      varied from small specks of calcification (2-3 mm) to large calcified bodies (1-2
      cm) with a typical "cluster" appearance. Conventional arthrography and
      computerized arthrotomography (performed on 3 patients) demonstrated the
      intraarticular site of calcified bodies as filling defects at hypertrophic
      synovial recesses. CT and MRI (performed on 4 patients) allowed easier
      demonstration of calcified/ossified bodies and of their relationships with
      articular structures. Moreover, synovial proliferation and cartilagineous nodules
      obliterating articular spaces, synovial recesses and juxtaarticular bursae were
      depicted. In particular, MRI allowed the differentiation not only of the
      different stages of the disease, but also of the idiopathic from the secondary
      forms. MRI plays therefore a fundamental role in the diagnosis of idiopathic
      synovial osteochondromatosis, directly influencing surgical planning, i.e.,
      removing articular loose bodies with partial or total synoviectomy by means of
      arthroscopy.

PMID- 7644725
TI  - [Ultrasonic diagnosis of "hematoma" of the sternocleidomastoid muscle].
AB  - Fifty-five patients (38 and 17), whose age ranged 14 to 153 days, with a clinical
      suspicion of sternocleidomastoid mass, were examined with US. Neck movements were
      impaired in all patients and 6 of them exhibited no clinically palpable mass.
      Sternocleidomastoid masses were detected in 50 patients. Other neck masses
      (lymphadenopathy, neuroblastoma, lymphangioma) were demonstrated in the remaining
      5 patients. US sensitivity was confirmed to be higher than that of clinical
      palpation in detecting the masses. Our results show that males (69%) and the
      right side (80%) were mostly affected. The sternal head (92%) and the lower third
      of the muscle (88%) were most commonly involved. Forty-four masses (88%) had
      homogeneous echostructure and their echogenicity relative to normal muscle was
      mostly isoechoic in 33 patients (66%) and hyperechoic in 11 patients (22%). Six
      masses (12%) had a patchy echotexture and mixed echogenicity. No cases of mostly
      hypoechoic echotexture or intralesional calcifications were observed. The mass to
      muscle ratio in the largest transverse sections ranged 25-175% (mean: 95%).
      Sternocleidomastoid masses disappeared in all 50 patients within their 6th month
      of age. US is confirmed as a valuable tool to diagnose and follow-up
      sternocleidomastoid masses.

PMID- 7644726
TI  - [Pulmonary tuberculosis in non-immunocompromised patients. Current radiologic
      features].
AB  - Sixty-four non-immunocompromised and adult patients with proved tuberculosis were
      examined. Twenty-three of them had bacteriologic confirmation with sputum
      examination, 7 with biopsy, 8 with bronchoscopy and bronchial lavage, 3 with
      pleural effusion examination and 3 with specific ex-juvantibus therapy. Fifteen
      patients had positive Mantoux skin tests. Thirty-nine patients had primary and 25
      postprimary tuberculosis. All patients underwent chest radiography and 37
      underwent also CT scans of the chest. The radiographic findings in primary
      tuberculosis were: 33 parenchymal consolidation patterns (in 24 patients), more
      frequent in the upper (20/33) than in the lower (13/33) lobes, with cavitations
      in 16 cases; 2 miliary patterns; 4 atelectasis cases; 4 intrathoracic
      adenopathies and 11 pleural effusions. The radiographic findings in postprimary
      tuberculosis were: 32 parenchymal consolidation patterns (in 19 patients), more
      frequent in the upper (27/32) than in the lower (5/32) lobes, with cavitations in
      7 cases; 2 tuberculomas; 1 miliary pattern; 1 atelectasis; 5 pleural effusions
      and 1 pericardial effusion. Thus, we can conclude that in our series both primary
      and postprimary tuberculosis appear mostly as upper lobe consolidation, with
      cavitations especially in the primary form, often with pleural effusion and
      sometimes with intrathoracic adenopathies. Primary tuberculosis is most frequent
      in adult men. Finally, lower lobe consolidations or less typical radiographic
      patterns are observed, e.g., atelectasis, adenopathies or pleural effusion with
      no parenchymal changes, which can mimic other diseases and thus delay the
      diagnosis.

PMID- 7644727
TI  - [Preoperative role of computerized tomography in videothoracoscopic lung
      surgery].
AB  - Video-assisted thoracic surgery (VATS) is used in a growing range of pulmonary
      and mediastinal conditions. By avoiding thoracotomy, VATS is minimally invasive
      and allows shorter postoperative hospitalization. The advantages of video
      assisted thoracoscopic techniques are obvious in the patients with severe
      cardiorespiratory failure. We investigated the role of CT before VATS. From
      September, 1991, to January, 1994, two hundred and eight patients were submitted
      to VATS: 80 pleurectomies, 63 lobectomies, 42 wedge resections, 11 bullectomies,
      8 biopsies and 4 pneumonectomies were performed in patients with diffuse lung
      disease. All patients underwent conventional CT and an additional HRCT was
      performed in 164 patients. Bullae site, number, characteristics and size must be
      assessed. The possible relationship of bullae to impaired respiratory function
      must be studied. When nodules are present, their site, depth and relationship to
      fissures must be defined. With small and deep-seated nodules a thin snap-open
      mandrel device should be used for intraoperative detection. When lobectomies are
      contemplated, fissures must be accurately studied to assess their integrity and
      whether they completely separate the lobes. Fibrous adhesions can prevent
      pulmonary collapse; unfortunately, some of them cannot be detected by CT. Another
      limitation is the difficulty in assessing whether fissures are incomplete. To
      conclude, CT integrated with HRCT provides useful information for correct video
      assisted thoracic surgical management.

PMID- 7644728
TI  - [Diagnosis of mycoplasma pneumonia in children: which is the role of thoracic
      radiography?].
AB  - Despite its frequency, pneumonia is often surprisingly difficult to diagnose in
      children and young adults. In particular, the etiologic agent of pneumonia is
      difficult to recognize in an early stage, which obviously implies an empirical or
      delayed treatment. Chest radiography is one of the most common procedures
      required when pneumonia is suspected. This retrospective study was carried out to
      investigate the capabilities of chest radiography to identify the specific
      patterns of mycoplasma pneumonia in children. The chest radiographs of 76
      children and adolescents (aged 4.2 to 16.4 years) with a radiographic diagnosis
      of pneumonia were reviewed. All patients were tested twice for serum
      antimycoplasma antibodies. Thirty-eight subjects (50%) with markedly increased
      antimycoplasma antibody levels were diagnosed as having mycoplasma infection. In
      the remaining 38 patients, viral (22 patients, 29%), bacterial (13 patients, 17%)
      and mixed (3 patients, 4%) infections were diagnosed on the grounds of clinical
      and laboratory data. Parahilar peribronchial infiltrates were found to be
      associated with both viral and mycoplasma infections, whereas segmental or lobar
      consolidation was associated with bacterial, viral and mycoplasma infections.
      Reticulonodular infiltrates were a specific pattern of mycoplasma pneumonia. The
      authors conclude that, in the presence of a reticulonodular infiltrate in a lobe,
      mycoplasma pneumonia can be confidently diagnosed.

PMID- 7644729
TI  - ["Uncompensated" small bowel obstruction in adults. Ultrasonographic findings of
      free fluid between loops and its prognostic value].
AB  - Plain abdominal film is the method of choice in the assessment of intestinal
      obstruction. This technique exhibits some limitations and must be frequently
      correlated with other diagnostic tools. Of them, US has been recently reported to
      allow the morphofunctional study of intestinal loops with high accuracy.
      Nevertheless, the literature on the usefulness of US disregards a sign of great
      interest, i.e., extraluminal fluid between bowel loops. Our personal experience
      in 56 adult patients with surgically confirmed small bowel obstruction suggests
      that this findings, demonstrated by US in 43 patients (73%), identifies early
      intestinal wall damage with high sensitivity. US, depicting fluid between bowel
      loops, can distinguish the various stages of obstruction, with major consequences
      on clinical management. US and plain abdominal film findings allowed us to
      distinguish three stages of obstruction: simple obstruction (15/56 patients,
      27%), uncompensated obstruction (26/56 patients, 46%), and complicated
      obstruction (15/56 patients, 27%). These three evolutive stages exhibit different
      severity and require different surgical approaches.

PMID- 7644730
TI  - [Endoanal ultrasonography, defecography, and enema of the colon in the radiologic
      study of incontinence].
AB  - In the last 3 years, the authors examined 564 patients with disturbed anorectal
      function. Of 41 incontinent subject in this series, 30 were retrospectively
      analyzed to assess the diagnostic contribution of double contrast barium enema,
      defecography and endoanal sonography. The authors propose a classification of
      fecal incontinence based on imaging findings: indeed, rectal incontinence can be
      distinguished from pelvic and sphincteral incontinence. Large bowel enema and
      defecography are the examinations of choice if rectal incontinence is suspected
      on the basis of clinical history and possible endoscopic, manometric and
      electromyographic findings. Defecography is suggested if pelvic incontinence is
      suspected, while anal endosonography is the exam of choice in case of suspected
      sphincteral incontinence. Especially thanks to the recent availability of the
      latter technique, today radiologists can directly visualize the anal sphincteral
      apparatus and its lesions, yielding objective evidence of this type of
      incontinence too. The authors report on both limitations and indications of each
      diagnostic method and conclude by stressing the fundamental role diagnostic
      imaging plays today in the study of this disorder.

PMID- 7644731
TI  - [Diagnostic value of computerized tomography in acute appendicitis in adults].
AB  - The diagnosis of acute appendicitis is generally based on clinical and laboratory
      findings. In 1/3 of the cases, acute appendicitis presents atypically and,
      consequently, the contribution of the radiologist becomes necessary. Conventional
      radiologic methods, i.e. plain abdominal film and barium enema, generally yield
      aspecific and indirect information. In contrast, the modern methods of cross
      sectional imaging, i.e. sonography and Computed Tomography (CT), allow to
      identify, directly and accurately, the inflammation of appendix and
      periappendiceal tissues. We report our experience with 25 cases of surgically
      confirmed adult acute appendicitis studied with abdominal CT examination. CT was
      usually performed with contiguous 5-mm-thick scans and with oral and intravenous
      contrast agent administration. CT showed abnormal appendix (72% of cases),
      pericecal or periappendiceal inflammatory infiltration (68%), phlegmon (20%),
      appendicoliths (16%), abscess (12%). CT was diagnostic for appendicitis in 21
      cases (84%) and suggestive of it in 4 cases (16%). CT is an interesting
      diagnostic alternative to US in the assessment of clinically questionable cases
      of appendicitis. Furthermore, it is the method of choice in the analysis of
      complicated appendicitis and in the percutaneous management of periappendiceal
      abscesses.

PMID- 7644732
TI  - [Computerized tomography in the assessment of obstructive jaundice caused by
      hepatic hydatid cysts].
AB  - This paper reports on the CT findings of obstructive jaundice caused by hydatid
      cysts of the liver, which are an unusual event occurring in 5-10% of cases. Thus,
      only a few reports can be found in the literature dealing with the CT features of
      this syndrome. Eight patients with obstructive jaundice were selected from 87
      patients with hydatid disease of the liver and examined with CT. The CT diagnosis
      of rupture into the largest bile ducts is based upon the demonstration of hepatic
      hydatid cysts together with intrabiliary hydatid sand, membranes and scolices
      and/or the identification of parietal discontinuity with communication between
      the cyst and the biliary tree. Rupture into the largest bile ducts was
      demonstrated in 7 patients. The following CT patterns were observed: 1)
      intrahepatic biliary tract dilatation (all cases); 2) extrahepatic biliary tract
      dilatation (6 cases); 3) cyst wall interruption (5 cases--in 3 of them the
      communication between the cyst and the dilated bile duct was demonstrated); 4)
      daughter cysts, fragmented membranes or hydatid sand in the biliary tree (5
      cases); 5) hydatid material in the gallbladder (1 case) and, finally,
      disappearance of the daughter cyst visible on a previous CT examination (1 case).
      In another patient, the diagnosis of compressive jaundice without biliary
      communication was suggested because a bulky hydatid cyst was found near the hilum
      of liver. CT findings were confirmed with ERCP or at surgery. CT failed to reveal
      small tears with minute biliary radicles, which are usually asymptomatic, whose
      diagnosis could be made only with preoperative cholangiography. Hydatid cysts of
      the liver can cause obstructive jaundice because of main bile duct compression or
      of large bile duct perforation with consequent passage of hydatid material into
      the biliary tree. This complication should be promptly managed surgically to
      avoid potentially fatal complications, which makes a preoperative diagnosis
      essential.

PMID- 7644733
TI  - [Computerized tomography with lipiodol in the assessment of hepatocellular
      carcinoma].
AB  - In this paper we report the results obtained with Lipiodol CT in 39 patients with
      hepatocellular carcinoma (HCC). All patients had focal or multifocal nodular HCC
      with FNB confirmation and were all submitted to CT 15-20 days after the injection
      of Lipiodol in common or proper hepatic arteries during an angiographic maneuver.
      Lipiodol CT showed all the lesions US had demonstrated and depicted more lesions
      in 12 patients (30.7%)--67 lesions in all. The lesions demonstrated by Lipiodol
      CT were always smaller than 2 cm: 9/12 had been missed by US, 6/12 by CT and 7/12
      by arteriography. In 34/67 lesions (50.7%) enhancement was homogeneous, in 29/67
      (43.2%) inhomogeneous and in 4/67 cases (5.9%) Lipiodol was not retained.
      Lipiodol uptake depended on lesion size: if the lesion was 1-2 cm, uptake was
      homogeneous, while bigger lesions exhibited inhomogeneous uptake. Lesions bigger
      than 4 cm exhibited no Lipiodol uptake and were necrotic. A surgical resection
      was performed in 21/39 patients (53.8%). To conclude, Lipiodol CT is a valuable
      technique in the preoperative screening of HCC, particularly in the detection of
      additional lesions: in our series they were demonstrated in 30.7% of patients.

PMID- 7644734
TI  - [Comparison between portography-CT and lipiodol-CT in the staging of
      hepatocellular carcinoma].
AB  - Eighteen patients (13 men and 5 women) with uni- and multifocal hepatocellular
      carcinomas (HCC) were examined. Mean patients age was 63.3 years (range: 47-74
      years). All patients had alcoholic or posthepatitis cirrhosis; they were
      submitted to both CT during arterial portography (APCT) and Lipiodol-CT. The
      diagnosis of HCC was confirmed by fine-needle biopsy (FNB) in all cases. APCT and
      Lipiodol-CT results were compared for number, size and site of lesions-32 lesions
      in all. APCT demonstrated all the lesions: 9 of them were smaller than 2 cm, 14
      ranged 2-5 cm and 9 were bigger than 5 cm; moreover, APCT demonstrated other
      lesions in 3/18 patients (16.6%) which had been missed by US, CT and angiography.
      Also Lipiodol-CT demonstrated all the 32 lesions and showed smaller lesions in
      4/18 patients (22.2%); these nodules were smaller than 2 cm. Based on APCT
      results 11/18 patients (61.1%) were considered operable, vs. 7/18 patients
      (38.8%) based on Lipiodol-CT results. To conclude, both APCT and Lipiodol-CT are
      useful in the preoperative staging of HCC; Lipiodol-CT is preferable to APCT in
      the study of lesions smaller than 2 cm.

PMID- 7644735
TI  - [Follow-up with Doppler color ultrasonography of patients treated with
      transjugular intrahepatic portosystemic diversion].
AB  - We investigated both reliability and limitations of color flow duplex US (CFDU)
      during the preoperative period and in the follow-up of the patients submitted to
      transjugular intrahepatic portosystemic shunt (TIPS). MATERIAL AND METHODS. Sixty
      six patients suffering from cirrhosis underwent TIPS. Twenty-seven patients were
      excluded from the trial, as they were treated in other hospitals and submitted to
      different follow-up. Twenty-four hours before and 48 hours after TIPS, and at 3,
      6 and 12 months' intervals during the follow-up, the mean flow rate was measured
      in the main portal vein and in the stent; the reappearance of ascitis was
      monitored by the same operator with CFDU. Six and 12 months after TIPS, all
      patients underwent venography and endoscopy. RESULTS. In 25 cases (64%), both
      CFDU and venography confirmed shunt patency. In these patients, the flow rate in
      the main portal vein and stent remained constantly high. In 9 patients (23%),
      CFDU diagnosed a stenosis on the basis of a marked reduction in the mean flow
      rate in the main portal vein (p < 0.001), which in 2 patients returned to pre
      TIPS values, and in the stent proximal to the portal vein (p < 0.001). In 2
      patients (5%), the obstruction was characterized by a return to pre-TIPS values
      in the portal vein and by the absence of any flow in the stent. Velocimetric
      sampling in the stent proximal to the vena cava had poor statistical
      significance. Venography confirmed the flowmetric results in all but 3 patients
      (7%). CONCLUSIONS. On the basis of our data, CFDU exhibited about 100%
      sensitivity, 89% specificity and 92% accuracy in the diagnosis of TIPS
      stenosis/obstruction. We therefore consider CFDU a useful tool in the follow-up
      of the patients submitted to TIPS, angiography being suggested only when needed
      on the basis of CFDU and/or endoscopic findings.

PMID- 7644736
TI  - [Assessment of renal function using low doses of paramagnetic contrast media].
AB  - Dynamic MR techniques with Gd-DTPA bolus administration can be used to study
      renal perfusion and function. In previous studies, the concentration of Gd-DTPA
      injected was never lower than 0.1 mmol/kg: as a result, depending on the magnetic
      susceptibility effect, renal signal intensity reduced in the early phases, right
      after contrast agent injection. To prevent signal intensity from reducing in the
      early phases, in our study we used a concentration of 0.05 mmol/kg. Qualitative
      and quantitative evaluations were performed. Seven healthy subjects and 14
      patients with different degrees of renal insufficiency were enrolled in the
      study. All exams were performed using an 0.5-T magnet (Philips Gyroscan T5, II),
      with 15 mT/m gradient power. Signal intensity measurements at the cortical,
      external medullary and internal medullary levels, allowed the drawing of curves
      typical of each degree of renal insufficiency which correlated well with nuclear
      medicine (scintigraphy) findings. The qualitative evaluation provided results
      comparable with scintigraphic findings in all 7 normal subjects, in 3 of 4 cases
      of moderate renal insufficiency, in all 7 cases of moderate/severe renal
      insufficiency and in the only case of severe renal insufficiency. To conclude,
      this trial demonstrates the feasibility of MR studies of renal function, which
      provide morphological and functional pieces of information. Low concentration Gd
      DTPA is decisive to avoid the magnetic susceptibility artifacts observed in
      previous studies.

PMID- 7644737
TI  - [Percutaneous vertebral biopsy. Assessment of results].
AB  - The results were reviewed of 81 percutaneous trephine biopsies performed under
      fluoroscopic or CT guidance from January, 1989, to August, 1994, in 78 patients
      with thoracic or lumbar vertebral lesions. All the patients presented abnormal
      findings at conventional radiography and questionable CT or MR findings. A fine
      needle sample was obtained as a complementary tool in 9 patients and material for
      microbiologic culture in 5 patients. Clinical and pathologic findings were
      correlated for each patient. Biopsy always permitted to obtain sufficient
      material for the histologic examination; its overall accuracy was 91%. The
      technique exhibited the highest diagnostic sensitivity in vertebral tumors (100%)
      and the lowest sensitivity in vertebral infections (69%). Complementary fine
      needle sampling was useful especially in small osteolytic lesions, while the
      microbiologic examination was often negative. There was only one pneumothorax due
      to the maneuver. To conclude, percutaneous trephine biopsy of thoracic and lumbar
      spine lesions is a valuable tool for tumor diagnosis which usually spares the
      patients open surgery.

PMID- 7644738
TI  - [Chemoembolization of hepatocarcinoma. Six years' experience].
AB  - This study was aimed at retrospectively assessing the effectiveness of
      transarterial chemoembolization by reviewing our six years' experience. From
      January, 1988, to December, 1993, chemoembolization was performed in more than
      400 patients. Of them, 321 patients with complete follow-up were selected. The
      treatment was retrospectively analyzed according to survival rates. The average
      survival of chemoembolized patients is 12 months after the first treatment
      session. Average survival rates in Child A, B and C patients were, respectively,
      13.79, 11.2 and 6.01 months. The patients were also divided according to tumor
      spread and the results follow: patients with single localizations had 15.19
      months' survival, those with multiple localization 12.06 and those with tumor
      spread had 9.51 months' survival. The patients were divided into two groups:
      complete chemoembolization (group A) and incomplete chemoembolization (group B).
      The average survival was 15.95 months for 160 group A patients and 10.11 months
      for 161 group B patients. As for the number of chemoembolization sessions, 123
      patients underwent only one session, 112 patients two sessions, 70 patients
      three, 12 patient four and 4 patients five sessions--625 sessions in all.
      Chemoembolization was performed every 3-4 months and was always preceded by a CT
      exam. Our patients were compared with an untreated group where average survival
      was 6.32 months. The value of CT after the first treatment in predicting survival
      was also studied. Finally, the methods used in all treatment are reported on,
      together with the general results and those in the different classes of patients.

PMID- 7644739
TI  - [Non-surgical treatment of pseudoaneurysm of the hepatic artery and its
      branches].
AB  - The transcatheter embolization of hepatic artery pseudoaneurysms and of its
      branches is now considered the most effective tool for their treatment. These
      lesions are caused by abdominal traumas or inappropriate surgical treatment.
      These pseudoaneurysms must be treated promptly because they are at high risk for
      rupture, with subsequent complications such as hematemesis, hemobilia and
      hemoperitoneum. We treated 7 patients with pseudoaneurysms: 4 of them were in the
      right hepatic artery, 1 in a right hepatic artery branch, 1 in the common hepatic
      artery and 1 in the suprahilar hepatic artery. Two pseudoaneurysms were treated
      with Gianturco coils, 2 with Ivalon particles, 1 with Contour particles, 1 with
      fibrin particles and 1 with transcatheter occlusion with Bucrylat. Six of 7
      patients recovered completely after embolization and in 1 patient only subsequent
      surgery was required. The success rate of transcatheter embolization was 85%. In
      our personal experience and from international literature reports, percutaneous
      embolization emerges as the safest therapeutic approach to hepatic artery
      pseudoaneurysms, yielding optimal results. In particular, percutaneous
      embolization is indicated for intrahepatic pseudoaneurysms and extraparenchymal
      saccular pseudoaneurysms of the common hepatic artery. Moreover, this technique
      exhibits a lower complication rate than surgery, whose mortality rate ranges 15
      20%.

PMID- 7644740
TI  - [Automatic devices for histologic biopsy of the breast. Comparison of 2 systems].

PMID- 7644741
TI  - [Radiotherapy of stage T1 carcinoma of the glottis. Analysis of prognostic
      factors in 154 patients].
AB  - A retrospective study was carried out on a series of 154 patients affected with
      vocal cord cancer in stage T1 treated with definitive radiotherapy April, 1979,
      to November, 1991. According to the 1992 TNM classification (UICC), 121 patients
      were classified as stage T1a and 33 patients as stage T1b. All patients were
      treated using parallel opposed fields of a 60 cobalt unit. Field size ranged from
      16 to 30 square centimeters and the dose from 4400 to 7000 cGy, but only 15
      patients received less than 6400 cGy. All patients were treated with once-daily
      fractionation (200 cGy/day). Follow-up ranges from 25 to 123 months; the median
      is 63 months. We observed 14 local recurrences (9.0%), all but one within 36
      months from the end of treatment. Ten of 14 patients (71.4%) were rescued by
      surgery (8 patients underwent total laryngectomy and 2 conservative surgery); 13
      patients were lost for intercurrent deaths. The incidence of recurrences is 7.4%
      for T1a patients (9/121) and 15.1% for T1b patients (5/33). The total dose does
      not seem to be related to relapse rate since recurrences were found in 6.6% of
      patients after a dose < 6400 cGy and in 9.3% of patients who had received higher
      doses. In our experience, field size did not affect, treatment results (< 25 cm2:
      7.5% recurrences, > 25 cm2: 10.7%). Besides lesion volume, the main prognostic
      factor was overall treatment time. The incidence of failure was 3 times lower
      (5.8%) in the patients who completed the treatment within 7 weeks than in the
      patients whose treatment lasted more than 8 weeks (16.6%).

PMID- 7644742
TI  - [Hodgkin's disease in stages I and IIA. Analysis of results in a group of
      patients with a follow-up of at least 10 years treated at the onset of the
      disease with radiotherapy alone].
AB  - January, 1972, through December, 1982, ninety-four patients with Hodgkin's
      disease in stages I and IIA were treated in the Dept. of Radiation Oncology of
      the University "La Sapienza", Rome. All patients had a minimum follow-up of 10
      years. After careful clinical and surgical examinations comprehensive of
      laparosplenectomy, all patients were submitted to extended field radiation
      treatment. Ninety-one of 94 patients (97%) obtained complete remission. Overall
      survival at 10 years was 91% and independent of stage (94% in stage I and 87% in
      stage II), while relapse-free survival at 10 years did depend on stage (83% in
      stage I and 49% in stage II); the difference was statistically significant (p <
      0.01). Thirty-one of 94 patients relapsed, but fortunately 94% of them obtained a
      second complete remission after salvage chemotherapy. Our experience confirms the
      low tumorigenic potential of exclusive radiation therapy; only one of 4 secondary
      neoplasms (acute non-lymphatic leukemia) observed in this series had been treated
      with radiotherapy. The results of this study confirm the efficacy of exclusive
      irradiation in stage I patients, while treatment approach remains debated in
      stage II patients. The combination of short-time chemotherapy with curative
      irradiation is probably the best option to reduce both the incidence of
      recurrences and treatment-induced complications.

PMID- 7644743
TI  - [Brachytherapy of epistaxis in Rendu-Osler disease. Indications, technic,
      results].
AB  - Rendu-Osler disease is a clinical form characterized by skin, mucous and bowel
      teleangiectasias causing repeated bleeding, especially in the nasal region.
      Repeated epistaxis is controlled, however transiently, with electrocoagulation,
      laser therapy, embolization, mucous transplants and external radiotherapy or,
      more frequently, brachytherapy. The authors report on a Curietherapy technique
      based on the use of 192Iridium wires. The wires, which cannot be placed in
      parallel lines, must be positioned in three places after a fan-wise pattern: the
      first one on the floor, the second one along the anterior wall and the third one
      in between. The three wires are inserted into plastic tubes during fluoroscopy.
      The length of the wires is differentiated for greater dose distribution
      homogeneity. The dose given to the reference isodose--which is probably in
      contact with the mucosa--is 30 Gy. We performed 9 maneuvers in 6 patients and
      three of them were also treated in the contralateral nostril. Complete remission
      was seen in 4 patients. In 2 patients the response has lasted 18 and 32 months
      and 2 others have a shorter follow-up. In 5 patients we obtained a good response
      (mean: 58 months). Our results are in agreement with those in brachytherapy
      literature. Few trials are reported of external irradiation but in our personal
      experience, its results are poor. Brachytherapy effect is limited in time but
      yields major clinical benefits to the patient. Brachytherapy cannot replace other
      treatment methods and must therefore be considered as a palliative treatment
      which can improve patient's quality of life in time.

PMID- 7644744
TI  - [Late sequelae involving the breast after radiotherapy for lung metastasis of
      Wilms' tumor. Experience of the Florence Radiotherapy and analysis of the
      literature].
AB  - A growing number of children treated for malignant tumors has been cured thanks
      to progress in the field of pediatric oncology, and therefore long-term treatment
      sequelae have been more frequently observed. Fourteen of 65 pediatric patients
      with Wilms' tumor treated in Florence 1957 through 1978, developed lung
      metastases and six survived at least five years after treatment. Four of these
      long-term survivors are girls. This paper reports on the long-term sequelae
      observed in the breast of these four patients: three of them presented breast
      hypoplasia and one breast cancer. We discuss our personal experience and the
      relative literature, describing the relationship between given dose and the
      incidence of breast hypoplasia. Some hypotheses on the etiology of secondary
      cancer are also discussed.

PMID- 7644745
TI  - [Morpho-functional diagnostic imaging in the assessment of viable myocardium in
      patients with ischemic heart disease. Correlations between myocardial perfusion
      and regional function of the left ventricle].
AB  - Forty patients (38 men and 2 women, mean age 56 +/- 9 years) with angiographic
      evidence of coronary artery disease underwent 201Thallium myocardial scintigraphy
      and two-dimensional echocardiography. 201Thallium uptake and echocardiographic
      regional ventricular function were studied in corresponding myocardial segments.
      On exercise-redistribution 201Thallium imaging, 308 segments (51% of the total)
      had normal Thallium uptake, 48 (8%) exhibited reversible defects and 244 (41%)
      irreversible defects. Of the latter 244 segments with irreversible defects, 114
      (47%) exhibited increased tracer uptake (Re+) and 130 (53%) remained unchanged
      (Re-) after 201Thallium reinjection at rest. Regional ventricular function was
      significantly better in the segments with normal Thallium uptake than in the
      segments with reversible or irreversible defects (p < 0.001). Furthermore, the
      segments with irreversible defects Re- had impaired regional function compared to
      the segments with irreversible defects Re+ (p < 0.001). Coronary artery stenosis
      was significantly more severe in the segments with irreversible defects Re- (93
      +/- 16%) than in those with reversible defects (81 +/- 20%) and with irreversible
      Re+ defects (80 +/- 20%) (both p < 0.001). In conclusion, in coronary artery
      disease patients, exercise-redistribution 201Thallium cardiac imaging with
      reinjection at rest can identify severely ischemic but still viable myocardium
      and may be particularly useful in the prognosis of such patients.

PMID- 7644746
TI  - [Osteomyelitis on eosinophilic granuloma. Report of a case].

PMID- 7644747
TI  - [Vertebral spiculation in a case of intrathoracic extramedullary hematopoiesis.
      Computerized tomography findings].

PMID- 7644748
TI  - [Diagnostic imaging in congenital abnormalities of the posterior arch of the
      atlas. Report of 2 cases and review of the literature].

PMID- 7644749
TI  - [Metastatic alveolar filling from colo-rectal adenocarcinoma. Report of a case].

PMID- 7644750
TI  - [Report of a case of porto-mesenteric aneurysm associated with parietal
      calcification].

PMID- 7644751
TI  - [Hepatic artery aneurysm: imaging with magnetic resonance. Report of a case].

PMID- 7644752
TI  - [Abdomino-pelvic lipomatosis. Report of 2 cases studied with magnetic resonance].

PMID- 7644753
TI  - [Chronic colo-colic invagination in a case of Crohn disease].

PMID- 7644754
TI  - [Peliosis hepatis: semiology with ultrasonography, computerized tomography, and
      magnetic resonance. Report of 2 cases].

PMID- 7644755
TI  - [Diagnosis with computerized tomography and magnetic resonance of a case with
      double abdominal carcinoid tumor location and hepatic metastasis].

PMID- 7644756
TI  - [Duodenal duplication: integrated imaging].

PMID- 7644757
TI  - [Computerized tomography diagnosis of Caroli's disease. Report of a case].

PMID- 7644758
TI  - [Transrectal color Doppler in calcified neoplasms of the bladder. Report of a
      case].

PMID- 7644759
TI  - [Radiotherapy of an unusual case of Kaposi's sarcoma of the "classic" type
      located in the external ear].

PMID- 7644760
TI  - Development of new nephrons in adult kidneys following gentamicin-induced
      nephrotoxicity.
AB  - Gentamicin-induced nephrotoxicity results in necrosis of proximal tubular
      epithelial cells. In mammals, the injured nephron can be repaired by migration
      and division of surviving cells. We examined this repair process in the fresh
      water goldfish, Carassius auratus. Fish were given a single intraperitoneal
      injection of 50 mg/kg gentamicin and sacrificed at 1, 4, 14, and 21 days. Injured
      nephrons showed regeneration along the basement membrane several days following
      gentamicin administration. In addition, 2-3 weeks following the injection,
      entirely new nephrons formed in the renal interstitium. Development of new
      nephrons in adult fish kidneys provides an excellent model for studying renal
      development and toxicity, and could provide insights into new therapies for
      chronic renal disease.

PMID- 7644761
TI  - Renal fluid and electrolyte handling in streptozotocin-diabetic rats.
AB  - Male Sprague-Dawley rats (300-400 g) were made diabetic by an i.p. injection of
      streptozotocin (STZ, 60 mg/kg in citrate buffer, n = 8) to examine renal function
      in well-established diabetes mellitus. Vehicle-injected animals (n = 8) acted as
      controls. The mean weekly total amounts of food taken by control and STZ-diabetic
      rats did not differ, but diabetic rats exhibited diarrhea and drank more water.
      STZ-diabetic rats progressively lost weight from the first to the third week but
      gained weight in the fourth week. At 5 weeks the weight stabilized, plasma
      glucose concentration was elevated, and this was associated with increased kidney
      weight. The weekly urine volume from STZ-diabetic rats was elevated throughout
      the 5-week period of study and this was associated with significantly lower
      urinary outputs of Na+ and higher outputs of K+ than those of control animals.
      After 5 weeks of STZ diabetes, plasma corticosterone and aldosterone
      concentrations in unanesthetized rats did not differ significantly from values
      seen in controls. To examine renal function in more detail, groups of Inactin
      anesthetized 5-week STZ-diabetic rats (n = 7) and control rats (n = 7) were
      placed on continuous jugular infusion of 0.077 M NaCl at 150 microL/min for 8.5
      h. Following a 3.5-h equilibration period, urine flow and Na+, K+, and Cl-
      outputs were determined for the subsequent 5-h period, with mean arterial
      pressure and glomerular filtration rate (GFR). STZ-diabetic rats voided
      significantly less of the infused fluid and the urinary excretions of Na+ and K+
      were lower than those of controls. Mean arterial blood pressure and GFR values in
      STZ-diabetic rats did not differ statistically from those seen in controls.
      Following hypotonic saline infusion for 8.5 h the levels of aldosterone were
      elevated significantly (p < 0.01) in STZ-diabetic rats by comparison with control
      animals (5.36 +/- 1.58 nmol/L, n = 7 vs. 2.36 +/- 0.12 nmol/L, n = 7). It is
      concluded that a challenge of hypotonic saline load to rats with 5 weeks of STZ
      diabetes mellitus elevates plasma aldosterone to reduce the ability to excrete
      Na+.

PMID- 7644762
TI  - Protection from cisplatin nephrotoxicity by A68828, an atrial natriuretic
      peptide.
AB  - The ability of a 13 amino-acid analog of atrial natriuretic peptide (ANP),
      A68828, to prevent development of cisplatin toxicity was evaluated in a rat
      model. ANP (1 microgram/kg/min), A68828 (10 micrograms/kg/min), A68828 (50
      micrograms/kg/min), or peptide buffer was given as an intravenous infusion over 1
      h beginning 15 min prior to an infusion of 5 mg/kg cisplatin. Animals receiving
      cisplatin plus peptide buffer vehicle developed predictable renal failure, with
      mean plasma creatinine and blood urea nitrogen concentrations of 1.09 +/- 0.09
      mg/dL and 50.13 +/- 5.96 mg/dL, 72 h after treatment. ANP and A68828 (10
      micrograms/kg/min) attenuated the increase in these indices of nephrotoxicity
      (mean plasma creatinine 0.86 +/- .06 mg/dL and 0.76 +/- 0.11 mg/dL,
      respectively). Surprisingly, the higher dose of A68828 (50 micrograms/kg/min) did
      not reduce cisplatin nephrotoxicity (72-h plasma creatinine 1.61 +/- 0.34 mg/dL).
      These results indicate that a short-term infusion of ANP or the analog A68828 can
      reduce the severity of cisplatin toxicity. At high doses of A68828 the beneficial
      effects of treatment may be lost.

PMID- 7644763
TI  - Antimyeloperoxidase antibodies induce neutrophil adherence to cultured human
      endothelial cells.
AB  - Antimyeloperoxidase autoantibodies are found in the sera of some patients with
      glomerulonephritis and systemic vasculitis. Previously, we demonstrated that they
      were able to stimulate neutrophils to damage cultured human endothelial cells. We
      now report that antimyeloperoxidase antibodies are able to stimulate neutrophils
      to adhere to cultured human endothelial cells. Immunoglobulin G purified from
      myeloperoxidase-antineutrophil cytoplasmic autoantibody positive sera increased
      adherence to 331 +/- 60% of unstimulated controls. In a similar manner, rabbit
      antimyeloperoxidase enhanced neutrophil adherence. Stimulating the endothelial
      cells with 10 micrograms/mL endotoxin enhanced antimyeloperoxidase stimulated
      adherence. In the presence of a CD18 blocking antibody (MoAb 60.3),
      antimyeloperoxidase-stimulated adherence was significantly decreased. These
      results add further understanding to the antimyeloperoxidase-stimulated
      neutrophil-endothelial cell interaction and further support the hypothesis that
      antimyeloperoxidase autoantibodies are of pathogenic import in glomerulonephritis
      and vasculitis.

PMID- 7644764
TI  - Risk factors and outcome of 107 patients with decompensated liver disease and
      acute renal failure (including 26 patients with hepatorenal syndrome): the role
      of hemodialysis.
AB  - The prognosis of acute renal failure in patients with preexisting liver
      decompensation is poor, and hemodialysis is considered futile, especially for
      hepatorenal syndrome (HRS). Since we observed a more favorable outcome in some
      patients, we retrospectively evaluated 107 patients with decompensated liver
      disease and acute renal failure (serum creatinine > 200 mumol/L) treated at the
      medical department of a university hospital in a 10-year period (1980-1990). HRS
      in the strict sense (urine-Na < 20 mmol/L while on furosemide) was diagnosed in
      26 of 107 patients (24%). Renal function remained compensated in 25 patients,
      while 82 patients fulfilled the criteria for dialysis treatment (creatinine > 500
      mumol/L and/or diuresis < 500 mL/day). In contrast to the current doctrine, 38 of
      the 82 patients were given hemodialysis (46%). Using the Cox proportional hazard
      model, the relative risk (presence vs. absence of a risk factor) of dying was
      increased 8.2-fold (3.9-17.2) in patients with thrombocytopenia < 100/nL, 3.9
      fold (1.4-11.3) in those with hepatic encephalopathy and prothrombin time < 30%,
      2.8-fold (1.6-4.8) in patients with malignoma, and 2.7-fold (1.5-4.8) in patients
      not submitted to dialysis despite its indication. In the CART statistics
      (classification and regression trees), the 33 patients with the poorest outcome
      were characterized exclusively by thrombocytopenia < 100/nL. HRS in the strict
      sense was not an independent risk factor. The CART group of 43 patients with
      favorable prognosis (compensated renal failure or treatment by hemodialysis,
      absent malignancy) had a 1-year survival rate of 38%. We conclude that
      thrombocytopenia, encephalopathy, and malignoma, but not HRS per se, are fatal
      signs that make hemodialysis futile in patients with acute renal failure and
      decompensated liver disease.

PMID- 7644765
TI  - Acute renal failure in pregnancy in South Africa.
AB  - This study compares our experiences of the incidence and etiology of acute renal
      failure in pregnancy (ARF-P) in patients requiring hemodialysis, a decade after a
      previous publication from our institution. A retrospective analysis of the
      hospital records of 42 patients with a diagnosis of ARF-P during a 3-year period
      from 1990 to 1992 was undertaken [16% of the total number of acute renal failure
      (ARF) patients needing hemodialysis]. The incidence of ARF-P (expressed relative
      to all cases of acute renal failure requiring hemodialysis) decreased from 24.6%
      (1978) to 16% (1992: p = 0.03). Preeclampsia-eclampsia (PE:E) replaced septic
      abortion as the principal cause of ARF-P. In those patients with PE:E,
      thrombocytopenia (platelet count < 150 x 10(9)/L) occurred in all, while 33%
      developed the HELLP syndrome (hemolysis, elevated liver enzymes, and low
      platelets). Ingestion of herbal toxins was noted mostly in patients with septic
      abortion. Maternal mortality was 5% and was due to multiorgan failure
      complicating septic abortion. The perinatal mortality of 55% occurred in women
      with early gestation, thrombocytopenia, and high serum creatinine levels. Acute
      renal failure in pregnancy continues to present a challenge in South Africa, a
      developing country. There were significantly more obstetric than gynecological
      causes in 1992 (p = 0.0003). This could be attributed to the steady decline in
      septic abortion since 1978. The main contributor to obstetric-related causes was
      PE:E. Greater emphasis should therefore be placed on detecting hypertension at
      antenatal visits.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7644766
TI  - Renal and hemodynamic effects of diltiazem after elective major vascular surgery-
      a potential renoprotective agent?
AB  - A postoperative study was done of the effects of an infusion of diltiazem (DTZ),
      1 microgram.kg-1.min-1 after a bolus dose of 0.28 mg.kg-1 on renal function and
      hemodynamics in 10 patients who were operated with insertion of an abdominal
      aortic graft. Urine flow, glomerular filtration rate (GFR) by inulin clearance,
      and renal plasma flow (RPF) by PAH clearance and fractional excretion of
      electrolytes and osmols were measured for three periods of 20 min during infusion
      of DTZ, in the morning after surgery. Systemic hemodynamic studies were conducted
      and serum levels of catecholamines were measured. GFR increased during the
      initial period of DTZ infusion. There were no significant changes during the
      study period in any of the other parameters, compared to baseline, except for a
      decrease in heart rate from 84 to 77 beats per minute. The absence of a sustained
      increase in GFR and a natriuretic and diuretic effect may possibly be ascribed to
      a preexisting nonconstricted status of the renal vasculature. The authors
      conclude that the dose of DTZ used in this study can be safely used for further
      investigations to elucidate the effects of peroperative infusion of DTZ on renal
      function in connection with major vascular surgery.

PMID- 7644767
TI  - A case of non-Hodgkin's lymphoma presenting with polyuria and acute renal
      insufficiency.
AB  - A case of non-Hodgkin's lymphoma presenting with polyuria, enlarged kidneys, and
      renal insufficiency is reported. The diagnosis was made by percutaneous needle
      biopsy of the kidney. Renal failure reversed and the kidneys regressed in size on
      exhibition of the first cycle of chemotherapy. The rarity of polyuria at
      presentation, the role of renal biopsy in the diagnosis, and the response of
      renal failure to specific chemotherapy are discussed.

PMID- 7644768
TI  - Renal failure and heatstroke.
AB  - We report a fatal case of heatstroke in an obese boy who developed multi-organ
      failure. Six other cases of exertional heatstroke admitted to our hospital over
      the last 5 years were also reviewed. All of them showed some degree of renal
      impairment. The causes of renal failure are multifactorial, with rhabdomyolysis
      being the major mechanism. All cases except one responded to alkaline diuresis
      without the need for dialysis. Continuous venovenous hemofiltration appeared to
      be a good alternative in hemodynamically unstable patients. Renal function
      recovered completely after varying intervals in all surviving cases.
      Interestingly, rhabdomyolysis in our heatstroke patients was usually associated
      with hypokalemia or normokalemia instead of hyperkalemia. Mortality in our series
      was largely related to the long duration of hyperthermia and coma, the severity
      of disseminated intravascular coagulation, and the presence of cardiogenic shock
      and severe acidosis.

PMID- 7644769
TI  - Doppler ultrasound in renal disease: not quite "the answer to a maiden's prayer".
AB  - Initial wild enthusiasm for the use of Doppler ultrasound in renal disease,
      particularly in renal transplants, led to claims that Doppler would enable
      diagnosis of various abnormalities without recourse to more invasive techniques.
      These claims have not been borne out by a more reasoned and scientific assessment
      of the role of Doppler ultrasound in the diagnosis of native and transplant
      kidney dysfunction. With the realization that changes in the Doppler findings
      merely reflect changes in renal blood flow induced by a variety of pathological
      processes has come a better understanding of how Doppler may be of benefit in the
      diagnosis and monitoring of these processes. The combination of duplex Doppler
      and color flow mapping with conventional B-mode ultrasound allows acquisition of
      both physiological and morphological information entirely non-invasively. Doppler
      ultrasound may not quite be "the answer to a maiden's prayer" in the evaluation
      of kidney disease but nevertheless represents a very useful tool in the
      nephrologist's investigative armamentarium, a tool which may be used repeatedly
      without detriment or risk to the patient.

PMID- 7644770
TI  - Asthma: basis and management at different ages.

PMID- 7644771
TI  - Adult Asian acute asthma admissions reassessed: Blackburn 1991-1992.
AB  - Two hundred and fifty-five admissions for acute asthma with a minimum 25% PEFR
      improvement in patients aged 15-44 years were studied in 1991-1992. Two hundred
      of these patients were in the white ethnic group (84 male; 116 female) with 33
      (17.4%) being readmissions (15 male; 18 female). Fifty-five admissions (19 male;
      36 female) were in the Indian subcontinent (ISC) ethnic group with 3 (5.5%; all
      female) readmissions. The readmission rate was significantly higher in the white
      ethnic group (chi 2 = 4.83; 0.05 < P < 0.01). Admission rates per thousand
      population in 5-yr cohorts were calculated from the 1991 Census data. The
      admission rate was higher in the ISC ethnic group in all cohorts except females
      aged 15-19 years, and was significantly higher in males aged 15-19 years and 40
      44 years, and in all four cohorts between 25-44 years in females. Initial PEFR
      and % initial PEFR/highest PEFR did not suggest increased severity of asthma in
      the ISC ethnic group.

PMID- 7644772
TI  - Bronchial hyperreactivity in patients with endobronchial tuberculosis.
AB  - Some patients with endobronchial tuberculosis (EBTB) have wheeze on physical
      examination and normal chest PA, which mimic bronchial asthma. Non-specific
      bronchial challenge tests have been used to confirm the presence of bronchial
      hyperreactivity, which is a hallmark of bronchial asthma. To evaluate the effect
      of endobronchial tuberculous inflammation on bronchial responsiveness to
      histamine, the provocation concentrations of histamine required to reduce FEV1 by
      20% of the pre-challenge baseline (PC20) were compared between patients with
      EBTB, patients with symptomatic bronchial asthma and normal, healthy controls.
      PC20 in EBTB patients (17.2 +/- 2.3 mg ml-1) and normal controls (19.5 +/- 1.4 mg
      ml-1) were significantly higher than in bronchial asthma patients (0.99 +/- 0.15
      mg ml-1). PC20 in EBTB patients was not affected by disease location in the
      bronchial tree was not correlated with FVC or FEV1. In conclusion, one should
      consider the possibility of EBTB for differential diagnosis from bronchial
      asthma, if airway responsiveness appears normal in wheezy patients.

PMID- 7644773
TI  - Eradication of contaminating Mycobacterium chelonae from bronchofibrescopes and
      an automated bronchoscope disinfection machine.
AB  - The results of a follow-up study concerning the decontamination of Mycobacterium
      chelonae subspecies abscessus from the bronchofibrescopes and the automated
      bronchoscope disinfection machine are described in this paper. After modification
      of the methods for disinfecting the bronchofibrescopes (adding a disinfection
      procedure with 70% alcohol before using the automated bronchoscope disinfection
      machine, increasing glutaraldehyde concentration to 3%, and changing the
      glutaraldehyde solution once a week), and the automated bronchoscope disinfection
      machine (recirculating used disinfectant), M. chelonae has not been detected from
      either the bronchofibrescopes or the automated bronchoscope disinfection machine
      (examined every 6 months for 4 yr by microscopy and cultures). Moreover, no M.
      chelonae has been clinically detected from bronchial washings for 4 yr.

PMID- 7644774
TI  - Functional residual capacity to thoracic gas volume (FRC:TGV) ratio in healthy
      neonates.
AB  - Gas trapping has been suggested to be common in healthy newborns in the immediate
      postnatal period. To determine the veracity of that finding, functional residual
      capacity (FRC) and thoracic gas volume (TGV) were measured in such a population
      and the FRC:TGV ratios were related to measurements of airway resistance (RAW).
      FRC was assessed by a helium gas dilution technique, TGV and RAW by
      plethysmography. Twenty-four healthy infants born at term were studied at a
      median age of 2 days (range 1-5 days). None had respiratory problems, nor had
      their mothers undergone invasive antenatal procedures. Their median FRC, which
      was 27.1 (range 23.8-32.0) ml kg-1, was significantly lower than their TGV
      (median 29.8, range 26-33 ml kg-1, P < 0.01). The mean 'within subject'
      difference between FRC and TGV was 2.5 (range 0.3-5.5) ml kg-1. The median
      FRC:TGV ratio was 0.93 (range 0.82-0.99). Eight infants had an FRC:TGV ratio less
      than 0.9, two of whom were studied on the first postnatal day. No infant with a
      low (< 0.9) FRC:TGV ratio had an abnormal RAW. The differences between FRC and
      TGV demonstrated in this study were smaller than documented in earlier series,
      suggesting the degree of gas trapping may previously have been over-estimated.

PMID- 7644775
TI  - Pilgrim's progress: the effect of salmeterol in older children with chronic
      severe asthma.
AB  - Twenty-four children aged 12-17 years entered a randomized, double-blind placebo
      controlled study investigating the use of salmeterol in chronic severe asthma. In
      addition to their usual medication, the children were given either placebo or 100
      micrograms salmeterol b.d. by dry powder inhalation. Treatment was continued
      throughout one term at a residential school for asthma. Symptom scores, peak
      expiratory flow rates, spirometry and quality-of-life scores were compared
      between the two treatment groups. One child withdrew during the run-in period.
      Twelve pupils received placebo and 11 pupils received salmeterol. There were
      consistent improvements in favour of salmeterol, reaching statistical
      significance for morning and evening peak flow rates and spirometry when measured
      on four occasions during the study period. There were no medication-related
      adverse events recorded and no pulse rate changes. Salmeterol (100 micrograms
      b.d.) is well tolerated and efficacious in older children with chronic severe
      asthma.

PMID- 7644776
TI  - Effects of the mixed phosphodiesterase III/IV inhibitor, zardaverine, on airway
      function in patients with chronic airflow obstruction.
AB  - Zardaverine is a selective inhibitor of phosphodiesterase (PDE) III and IV
      isozymes. It has been shown to exert potent bronchodilator effects in animals. In
      order to study the efficacy and safety in man, a phase II clinical trial in 10
      patients with partially reversible chronic airflow obstruction was carried out.
      The trial was designed as a double-blind, randomized, five-period change-over
      study. Zardaverine (at single doses of 1.5 mg, 3.0 mg, or 6.0 mg), salbutamol
      (0.3 mg) and placebo were administered by metered dose inhaler on separate days.
      As evaluated by spirometry over a time period of 4 h, salbutamol induced a
      significant bronchodilatation. In contrast, zardaverine did not improve airway
      function in these patients. Unwanted effects of the study medication were not
      observed.

PMID- 7644777
TI  - Raised plasma concentrations of brain natriuretic peptide in pulmonary arterial
      hypertension.

PMID- 7644778
TI  - Invasive aspergillosis after bilateral lung transplantation in cystic fibrosis.

PMID- 7644780
TI  - Bronchoconstriction following inhaled ethanol solutions.

PMID- 7644779
TI  - Bronchiectasis complicating rheumatoid arthritis.

PMID- 7644781
TI  - Non-tuberculous mycobacteria.

PMID- 7644782
TI  - [Septic shock: from basic research to patient's bedside].

PMID- 7644783
TI  - [Hepatitis C virus antibodies in alcoholic patients].
AB  - It has been reported that chronic alcoholics show a high prevalence of hepatitis
      C virus (HCV) infection, with a possible role in the pathogenesis and severity of
      underlying liver disease. Thus, the present study was aimed to evaluate the
      prevalence of HCV antibodies (anti HCV-Ab) in a group of patients admitted to an
      Internal Medicine Department, as well as to compare characteristics of anti-HCV
      Ab(+ve) respect to anti-HCV(-ve) patients. The presence of anti-HCV-Ab was
      prospectively studied in 180 alcoholic patients admitted during a 16-month period
      using a second generation ELISA. Intravenous drug abusers were excluded. Reasons
      for admittance were as follows: alcohol withdrawal syndrome (92 cases),
      complications of liver cirrhosis (mainly ascites) (54 cases), acute pancreatitis
      (12 cases) and miscellaneous causes (22 cases). Sixty-six patients were
      cirrhotics, 23 had fatty liver, 27 had liver fibrosis and 28 alcoholic hepatitis
      (36 patients were not evaluable concerning liver lesion). Twelve patients (6.7%)
      were anti-HCV-Ab(+ve). Prevalence was higher in patients admitted because of
      complications of cirrhosis (16.7%) than that of those admitted due to alcohol
      abstinence syndrome (1.1%, p < 0.01). Likewise, the proportion of HVC-Ab(+ve)
      patients was higher in patients with liver cirrhosis (16.7%) respect to those
      with lesser degrees of liver injury (1.3%; p < 0.01). In the latter group, the
      prevalence of anti-HCV-Ab(+ve) was similar to that of the normal population. Anti
      HCV-Ab patients were older than anti-HCV-Ab(-ve) cases.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7644784
TI  - [Proliferation of large granular lymphocytes in patients with systemic lupus
      erythematosus].
AB  - BACKGROUND: Large granular T lymphocytes (LGL) make up a small portion of
      cellular population in peripheral blood. An abnormal proliferation of LGL is
      detected together with cytopenic and other autoimmune disorders and is often
      associated with rheumatoid arthritis. The association with other autoimmune
      diseases, such as systemic lupus erythematosus, is poorly known. The clinical and
      immunological profile in five patients with SLE and LGL proliferation is here
      reported. MATERIALS AND METHODS: A clinical follow-up and prospective phenotypic
      study of mononuclear cells was conducted in patients with SLE for a period of 24
      months. LGL were identified on the basis of their shape and analyzed by flow
      cytometry as cells coexpressing thymic differentiation antigens (CD3 and CD4, or
      CD8) and NK cells CD16, CD56 or CD57). RESULTS: Five out of 43 patients with SLE
      showed recurrent proliferations of LGL (from 2 to 4 per patient) chronologically
      associated with lupus exacerbations. LGL represented 52 to 78% (mean +/- SD = 56
      +/- 8%) from the total of lymphocytes. The phenotype in proliferations was
      heterogeneous but it was consistent in later relapses in each patient (patient #1
      and #2: CD3+CD8-CD4+CD16+CD56+CD57-HLA/D+ patients #3 and #4: CD3+CD8+CD4
      CD16+CD56+CD57-HLA/DR+ patient #5: CD3+CD8+CD4- CD16+CD56+CD57-HLA/DR+patient
      5:CD3+CD8+CD4-CD16 +/- CD56-CD57+HLA/DR+). These five patients had long term SLE
      with a greater number of exacerbations and a tendency to develop hemocytopenias,
      requiring high doses of corticosteroids and even immunosuppressors to control
      their condition. CONCLUSIONS: Some patients with SLE develop LGL proliferations.
      The activity, clinical severity and hematological involvement seem to be
      associated with this immunological disorder, but the pathogenic significance and
      prognosis of these proliferations are still to be elucidated.

PMID- 7644785
TI  - [Acute nontraumatic myelopathies: a review of 36 cases].
AB  - The objective of this investigation was to know the features of acute
      nontraumatic myelopathies in our area, given the paucity of reported data.
      Therefore, 36 episodes of myelitis observed during a 15-year period at Hospital
      Nacional de Paraplejicos were retrospectively reviewed. Cases associated with
      multiple sclerosis were excluded. On etiological basis these disorders were
      classified in vascular (in its turn subclassified in surgical and non-surgical)
      and inflammatory myelopathies. The functional prognosis was poor. Two patients
      with non-surgical vascular myelitis suffered a second episode of spinal ischemia
      which deteriorated their conditions. The usefulness of NMR seems to be limited.

PMID- 7644786
TI  - [Bendazac hepatotoxicity: analysis of 16 cases].
AB  - Hepatic lesions induced by non-steroid antiinflammatory drugs are a common cause
      of disease, particularly among elderly patients. Although its clinical expression
      is polymorphous, occasional increases in serum transaminase values predominate.
      Sixteen cases of liver involvement by bendazac were studied. This NSAID is used
      in Spain for the treatment of cataracts, from a total of 112 patients observing
      such therapy. The clinical spectrum of liver disease induced by bendazac is
      discussed and emphasis is placed on the necessity to judiciously select the
      indications for NSAIDs.

PMID- 7644787
TI  - [Methotrexate treatment of amyloidosis secondary to rheumatoid arthritis].
AB  - Amyloidosis secondary to rheumatoid arthritis is a complication with a poor
      prognosis and as yet an undefined medical therapy. In the last decades the use of
      different cytostatics has been advocated to avoid renal function deterioration.
      The clinical characteristics and course in eight patients with amyloidosis
      secondary to rheumatoid arthritis are here reported after therapy with low dosage
      methotrexate. In twelve patients who followed a 12-month therapy a clinical
      improvement was observed, with a marked decrease in proteinuria; in one of them
      proteinuria disappeared. These results suggest that methotrexate at low doses
      might be an alternative in the early treatment of amyloidosis secondary to
      rheumatoid arthritis in patients with preserved renal function.

PMID- 7644788
TI  - [Right supraclavicular adenopathy].

PMID- 7644789
TI  - [71-year-old woman with progressive dyspnea and interstitial pattern].

PMID- 7644790
TI  - [Dental manipulation and pneumomediastinum].

PMID- 7644791
TI  - [Metrorrhagia in a 75-year-old woman with endometrial polyp].

PMID- 7644792
TI  - [Physiopathological and clinical aspects of nutrition in patients with chronic
      renal failure not undergoing dialysis].

PMID- 7644793
TI  - [Complications of oxygen therapy by a transtracheal catheter].

PMID- 7644794
TI  - [Residual risk of retrovirus transmission by transfusions].

PMID- 7644795
TI  - [The kidney in essential arterial hypertension: should microalbuminuria excretion
      be measured?].

PMID- 7644796
TI  - [Hepatitis E].

PMID- 7644797
TI  - [Aseptic arthritis and selective deficiency of immunoglobulin A. A pathogenic
      relationship? Report of 2 cases].

PMID- 7644798
TI  - [Blood lipids in hospitalized patients].

PMID- 7644799
TI  - [Phytobezoar in the terminal ileum simulating acute appendicitis].

PMID- 7644800
TI  - [Neuroradiological changes in a case of lumbosacral polyradiculopathy caused by
      cytomegalovirus in a patient with AIDS].

PMID- 7644801
TI  - [Internuclear ophthalmoplegia in relation to lidocaine and pentothal].

PMID- 7644802
TI  - [Importance of the sample size in clinical trials].

PMID- 7644803
TI  - [Heart transplantation].
AB  - Heart transplantation is presently the only treatment capable of substantially
      changing the natural history of endstage heart failure, achieving a 5-year
      survival rate of 60%. The relative scarcity of available donors is the main
      limitation to this procedure. The standard surgical technique is that referred to
      as "orthotopic", described by Shumway and Lower. Research efforts now focus on
      the design of more efficient methods of preservation that will permit longer
      storage periods once the grafts have been harvested. Rejection and infection are
      the most common causes of post-transplantation mortality. The "attenuation" of
      the immune response to prevent graft loss is achieved by administration of drugs
      such as cyclosporine A, azathioprine, steroids and antilymphocytic globulins,
      which constitute the basis for most immunosuppression protocols. Despite numerous
      proposals of methods for detecting rejection, endomyocardial biopsy continues to
      be the fastest and most efficient procedure and constitutes a standard tool for
      monitoring rejection. Graft vascular pathology or chronic rejection is the
      greatest threat to long-term survival of transplant recipients, 30% of whom are
      affected by this process after 5 years. Prospects for the future point in three
      different directions: research to design more powerful and selective
      immunosuppressive drugs, the development of totally implantable and autonomous
      artificial ventricular assist systems and the use of xenografts that have
      undergone genetic manipulations that eliminate interspecies immunological
      barriers.

PMID- 7644804
TI  - [Asymptomatic hypertrophic myocardiopathy. The arguments against its treatment].

PMID- 7644805
TI  - [Asymptomatic hypertrophic myocardiopathy. The arguments in favor of its
      treatment].

PMID- 7644806
TI  - [The diagnosis of myocardial damage during coronary angioplasty by the analysis
      of the isoforms of the enzyme creatine kinase MB].
AB  - BACKGROUND: The existence of myocardial damage during percutaneous transluminal
      coronary angioplasty (PTCA) is controversial. Mild elevations in creatine kinase
      (CK) activity and its isoenzyme MB (CKMB) in patients who underwent PTCA have
      been reported. However, other authors failed to confirm these elevations. The low
      sensitivity of total CK and CKMB activity for the detection of myocardial damage
      in different settings other than myocardial infarction might account for the
      controversial findings. Measurement of CKMB isoforms has been shown to have a
      higher sensitivity than the assessment of CK or CKMB activity for early diagnosis
      of myocardial infarction. Its sensitivity for the diagnosis of myocardial damage
      in settings other than infarction is not well described. OBJECTIVES: The aim of
      our study was two-fold: 1) to assess the incidence of myocardial damage after
      PTCA and 2) to compare the sensitivity of total CK and CKMB activity and
      measurement of CKMB isoforms for the detection of myocardial damage. METHODS: 14
      patients (11 men and 3 women) with chronic stable angina underwent PTCA. Two
      electrocardiographic leads were monitored from the beginning of the procedure
      until 30 minutes after the PTCA. ST segment shifts of at least 1 mm, lasting for
      more than 1 minute, were considered indicative of myocardial ischemia. The
      duration of ischemic episodes was measured from the onset of the ST shift until
      its return to baseline. Total ischemic time, in minutes, was the sum of the
      duration of every ischemic episode. Blood samples were drawn before PTCA and
      serially during the first 24 hours post PTCA. CK (normal < 200 U/l) and CKMB
      (normal < 14 U/l) activities were measured. The CKMB isoforms were separated by
      electrophoresis, measured by densitometric scanning and their ratio calculated
      (CKMB2/CKMB1 normal < 1.5). RESULTS: Vessels which underwent PTCA were: the left
      anterior descending artery (LDA) in 5 patients, the circumflex coronary artery
      (Cx) in 3 patients, right coronary artery (RCA) in 3 patients, LDA and Cx in 1
      patient and Cx and RCA in 2 cases. Eleven patients underwent balloon dilatation,
      1 underwent atherectomy (Rotablator) and two patients had treatment with both
      Rotablator and balloon angioplasty. Ischemic ST segment shifts were found in ten
      patients and the median of total ischemic time was 13.5 minutes (interquartile
      range: 2-15 minutes). Total CK and CKMB activities were within the normal range
      in every patient whereas in 7 patients (50%) the peak ratio CKMB2/CKMB1 was above
      the normal range. There were no differences in age, sex, number of vessels or
      lesions treated or in the time of balloon inflation between patients with and
      without abnormal CKMB2/CKMB1 peak. However, the ischemic time was significantly
      higher in patients with CKMB2/CKMB1 > 1.5 (median 15 vs 0 minutes; p = 0.023).
      CONCLUSIONS: Myocardial damage during PTCA is not an uncommon finding. The CKMB
      isoforms are more sensitive markers of myocardial damage during PTCA than total
      CK or CKMB activities.

PMID- 7644807
TI  - [Redundancy of the interatrial septum without associated congenital cardiopathy.
      Its prenatal echocardiographic diagnosis and follow-up].
AB  - INTRODUCTION AND OBJECTIVE: Aneurysm of the atrial septum at the level of the
      foramen ovale is reported commonly at the routine fetal echocardiographic
      examination. Cases with entire involvement of the atrial septum have been
      exceptionally reported. We described the data concerning the prenatal detection
      of a total redundancy of the atrial septum in 6 cases without congenital heart
      disease. METHODS: The gestational age was between 28 and 38 weeks, and none of
      the fetuses had evidence of heart defect. A routine fetal echocardiography was
      made in all the cases. Rhythm disturbances were studied by M mode. During the
      first three months of life, a cardiologic control was made in all the cases.
      RESULTS: The large displacement of the atrial septum towards the left atrium was
      clearly visualized in four-chambers view; by using Pulsed Doppler and Color flow
      mapping, the pulmonary venous return and mitral orifice flow were not impaired.
      Premature atrial beats were found in two fetuses and no hemodynamic disfunction
      was observed in all entire study group. Postnatal echocardiographic control was
      normal in all patients. The atrial septum becomes completely rectified with
      normal patency of the foramen ovale membrane in the newborn studies. The
      supraventricular extrasystoles were confirmed in the neonatal period. In both,
      the arrhythmia disappeared in a few days after delivery without treatment.
      CONCLUSIONS: Despite the benign follow-up in our cases, the unexpected presence
      of an extremely redundant atrial septum, leads to a close prenatal attention
      particularly in the presence of rhythm disturbance. The pathologic substrate of
      this anomaly might be an intrinsic alteration of the myocardial structure of the
      septum like seems demonstrated in the aneurysm circumscribed to area of the fossa
      ovalis [correction of fosa ovale]. The increase in the left atrial pressure after
      birth will produce a normal 2-D echo patterns in the newborn period.

PMID- 7644808
TI  - [The mitral valve apparatus in hypertrophic myocardiopathy: observations by
      transesophageal echocardiography].
AB  - INTRODUCTION AND OBJECTIVES: We analyzed the characteristics of mitral valve
      apparatus by transesophageal echocardiography in a consecutive series of patients
      with hypertrophic cardiomyopathy. METHODS: We performed a transesophageal study
      in 60 patients; 35 of them had intraventricular obstruction at basal state. The
      following measurements and observations were made in the frontal long-axis
      transesophageal plane: a) length of both mitral leaflets and dimensions of left
      ventricular outflow tract that were compared with those obtained from 25 normal
      subjects; b) structure involved in the systolic anterior mitral motion; c)
      mechanism of mitral regurgitation, and d) sequence of systolic events. RESULTS:
      Compared with control subjects (anterior mitral leaflet: 2.86 +/- 0.3 cm,
      posterior mitral leaflet: 1.62 +/- 0.2 and 1.7 +/- 0.2 cm, respectively; the
      mitral leaflets were longer in patients with and without subaortic obstruction
      (anterior leaflet: 2.3 +/- 0.1; posterior leaflet: 1.07 both, p < 0.01). Systolic
      anterior motion was observed in 49 patients, with mitral leaflet-septal contact
      in 87% of patients with obstruction and in 11% of nonobstructive patients (p <
      0.01). Structures participating in this phenomenon were: distal portion of the
      anterior mitral leaflet (77.5%), of both mitral leaflets (18.4%) and anomalous
      chordae (4.1%); in 5 patients the obstruction was located at a more distal level.
      Mitral regurgitation was observed in 43 patients; in 37 of them the jet was
      posteriorly directed in late systole. Patients with hypertrophic cardiomyopathy
      have longer mitral leaflets with frequent associated abnormalities suggesting
      that this disease is not confined to myocardium and that leaflet length is not
      the sole determinant of the obstruction; 2) in almost 80% of patients the
      systolic anterior motion was produced by the distal anterior mitral leaflet
      resulting in incomplete coaptation in mid-systole; 3) the sequence of systolic
      events was ejection/obstruction/leak.

PMID- 7644809
TI  - [Pulmonary hypertension and early mortality after orthotopic heart
      transplantation].
AB  - INTRODUCTION AND OBJECTIVES: To study the relationship between hemodynamic
      parameters before heart transplantation and the mortality rate at the first week
      posttransplant. METHODS: 85 patients had an orthotopic heart transplant. Before
      the operation we measured: vascular pulmonary resistance, index of vascular
      pulmonary resistance, pulmonary arterial pressure systolic and median and
      transpulmonary gradient. Ten patients with values of vascular pulmonary
      resistance higher than four Wood units and/or pulmonary artery systolic pressure
      higher than 60 mmHg, had a test of pulmonary vascular reactivity, the result of
      that test did not contraindicate the transplant. We used the Student's t test and
      chi 2 with continuity correction and the Fisher's exact test for the analysis of
      the data. RESULTS: During the study period eight patients were dead (9.4%). The
      causes of death were: acute disfunction of the graft, 5 patients; multiorgan
      failure, 2 patients and septic shock, 1 patient. We compared the parameters of
      both groups of patients live and dead and could find a significant difference
      between the data with higher values in the death group: pulmonary arterial
      systolic pressure (p < 0.01); pulmonary arterial median pressure (p < 0.03) and
      transpulmonary gradient (p < 0.02). We also saw that the relative risk of
      mortality was 10.4 when the pulmonary artery systolic pressure was > or = 50 mmHg
      and 5.7 when the pulmonary vascular resistance was > or = 5 Wood units.
      CONCLUSIONS: It is important a good evaluation of the pulmonary hemodynamic
      before the heart transplantation for a better selection of the receptor. The
      severe pulmonary hypertension (pulmonary vascular resistance > or = 5 Wood units
      or pulmonary artery systolic pressure > or = 50 mmHg) was associated with a
      higher rate of early death.

PMID- 7644810
TI  - [Pericardial constriction with predominant involvement of the left heart
      chambers].
AB  - Constrictive pericarditis is a common complication of purulent pericarditis and
      it can evolve to hemodynamic patterns different from the classical one. We report
      a patient that after purulent pericarditis, his clinical and hemodynamic features
      suggest isolated constriction of the left ventricle.

PMID- 7644811
TI  - [Coronary angioplasty in a case of dextrocardia with situs inversus and
      myocardial infarct].
AB  - Dextrocardia and situs inversus totalis is a rare congenital anomaly in adults.
      Usually, the patients have structurally normal hearts and experience normal
      longevity. The risk of coronary atherosclerosis is similar to that of the general
      population. However, the report of coronary angioplasty and/or coronary
      arteriography on patients with dextrocardia is scant. We describe herein a case
      of successful percutaneous transluminal coronary angioplasty to the right
      coronary artery. We comment the technical particularities of the procedure, and a
      review of the literature is made.

PMID- 7644812
TI  - [The rupture of a cardiac hydatid cyst located in the right ventricle].
AB  - Heart involvement in echinococcal disease is rare, but it is more infrequent the
      location of cysts in the right ventricle. We report a case of a male 35 years old
      with hydatid cysts located in the right ventricle. The condition was diagnosed by
      two-dimensional echocardiogram performed after the rupture of the cysts leading
      to massive pulmonary embolism and subsequently right heart failure. Early
      diagnosis appears mandatory in an attempt to modify, applying the appropriate
      therapy, the natural evolution of this potentially lethal condition.

PMID- 7644813
TI  - [Unilateral agenesis of the pulmonary branch. Its diagnosis by color echo-Doppler
      and nuclear magnetic resonance].
AB  - We present two symptomatic patients of five and six months old with unilateral
      agenesis of main pulmonary branch (right and left) without associated anomalies.
      The diagnostic was made with magnetic resonance imaging and two-dimensional
      echocardiographic with Doppler color flow. We think that the magnetic resonance,
      must be used with priority in this pathology for being a non invasive diagnostic
      method, that is able to diagnostic the basic cardiopathy and the intracardiac and
      extracardiac associated anomalies. His association with the Doppler
      echocardiography allow to ignore the arteriography upon to get a accurate
      diagnostic.

PMID- 7644815
TI  - [Cardiac rehabilitation].

PMID- 7644814
TI  - [Cardiac rehabilitation. Its historical evolution and current situation].
AB  - Cardiac rehabilitation is a part of secondary prevention of cardiovascular
      diseases. It started as physical exercise programmes after the acceptance of the
      early mobilization of myocardial infarction patients. The programmes and
      recommendations of the World Health Organization, reported in 1964 and
      thereafter, expanded the development of cardiac rehabilitation and on that time,
      the first clinical studies were published. Later on, some randomized clinical
      trials were reported, but their results were not conclusive. Recently, a meta
      analysis showed a reduction on mortality of 20-25% after cardiac rehabilitation
      programmes. The WHO Office at present, recommends the inclusion of rehabilitation
      programmes onto the secondary prevention measures for cardiac patients. The
      implementation of such programmes in our country must be considered as very
      necessary and beneficial.

PMID- 7644816
TI  - [The control of risk factors in cardiac rehabilitation programs].
AB  - Patients with ischaemic heart disease are at high risk of developing new clinical
      cardiac events and cardiac death in the following years. Appropriate Secondary
      Prevention Programs have proved to be useful both to slow the progression of
      coronary disease and to decrease the probability of new clinical events and the
      overall mortality. Cardiac rehabilitation programs constitute the best current
      approach directed to the modification of risk factors. The programs have not only
      significantly improved the risk profile of ischaemic patients but also have
      contributed to the acceptance of new healthy life style.

PMID- 7644818
TI  - [Occupational therapy in cardiac rehabilitation].
AB  - The occupational therapy in cardiac rehabilitation is aimed to decrease the
      physiologic and psychologic patient overwork, allowing the work return. It shows
      a more ergonomic way to do those dangerous tasks without risk. It is necessary
      because there are differences between the work done in the effort tests and his
      lifetime. The cardiac rehabilitation is an efficient share in coronary patient
      treatment and occupational therapy is a significant complementary procedure.

PMID- 7644817
TI  - [Psychiatry for cardiologists: psychological care for the coronary patient].
AB  - During the different post-infarction stages, the coronary patient can show
      different profiles of adaptation, requiring adequate therapeutic approaches. In
      the acute phase, anxiety and irritability are a common response. The handling of
      information and the use of anxiolytics are the therapeutic alternatives that can
      best improve the possible psychic instability of the patient. During the
      rehabilitation phase, it is frequent to find the presence of denial mechanisms as
      a defence against anxiety or depression. The use of antidepressant drugs will
      depend on the clinical situation of each patient. It is also necessary in this
      phase to deal with problems such as possible sexual disorders, as well as with
      the control of risk factors and the reintegration into family life. It is a
      question, in short, of achieving a healthier lifestyle and a better quality of
      life. In the long term, the aim would be focused on the return to work and on the
      follow-up of the patient, so as to avoid that he may come back to the lifestyle
      he was leading before his disease. Nowadays, as clinical cardiology has lost
      importance, giving way to invasive cardiology, it is necessary to restore the
      humanistic and psychological role of the cardiologist, focused on the
      cardiologist-patient relationship. The object of this paper is to underline the
      importance of the cardiologist in the psychiatric-psychological attention of the
      coronary patient.

PMID- 7644819
TI  - [Protocols of hospital rehabilitation in phases I and II].
AB  - We define the phase I as that in which the patients are into the hospital because
      an acute coronary event like myocardial infarction, or by surgery. It is also
      called hospital phase and lasts when the first exercise test is made. We define
      the phase II as that in which the patients increase their functional capacity and
      lasts when that increase is not necessary. Its duration is two or three months.
      It is also called convalescence phase. The aims of the physical training in the
      phase I are to avoid the damages of extensive rest in bed like muscle atrophies
      and calcium loss of the bones with important decrease of functional capacity and,
      in surgical cases, to avoid bronchial secretions, atelectases, phrenic paralysis
      and mobility damages secondaries to the scar. The physical training in the phase
      I begins 48 hours after the acute myocardial infarction or immediately after
      surgery, with light calisthenics and, when surgery, other specific exercises to
      avoid its specific described damages. A patient risk stratification can be made
      during the phase I following clinical criteria. The phase II begins with the
      first exercise test, made between the 10th and 15th days after infarction or
      between the 7th and 15 days after surgery or PTCA. This exercise test can
      evaluate the medical treatment, stratify the risk and determine the intensity of
      the exercise in this phase. The main aim in this phase is to improve the
      functional capacity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7644820
TI  - [Long-term cardiac rehabilitation].
AB  - Cardiac rehabilitation for life-time in a patient who has suffered coronary
      pathology is considered as appropriate. The reasons for such an opinion are
      given, as well as the two most indicated courses of action, being this
      rehabilitation at home and coronary clubs.

PMID- 7644821
TI  - [Cardiac rehabilitation. Other protocols].
AB  - Cardiac rehabilitation programmes and secondary prevention programmes vary
      according to the type of cardiopathy, to the functional state and to the physical
      characteristics of the subject. On many occasions, they depend on the material
      resources and on the staff of the centre offering this type of therapeutic
      action. A summary of different ways of performing cardiac rehabilitation in our
      country is given.

PMID- 7644822
TI  - [Cardiac rehabilitation in the elderly patient].
AB  - The number of people over 65 is progressively increasing. In this group, the
      incidence of ischemic cardiopathy is very high and nowadays revascularization
      procedures are being used more and more. Cardiac rehabilitation programmes have
      proved to be an efficacious therapy in ischemic cardiopathy. These programmes
      initially excluded high-risk patients and elderly patients. In the last years, it
      has been confirmed that the benefit obtained in people over 65 is at least
      similar to the benefit observed in younger patients, with no greater number of
      complications. The aims of a cardiac rehabilitation programme are to improve the
      prognosis and quality of life. In elderly patients, the aims are similar, but
      special stress is laid on improving their quality of life and obtaining the
      maximum survival rate free of incapacitation.

PMID- 7644823
TI  - [Cardiac rehabilitation in coronary surgery].
AB  - In the present study were described both the indications and protocols which are
      used in the main units of cardiac rehabilitation of Spain. The needs for a
      unification in the rehabilitation programmes was stressed. In fact, the author
      underlines the opportunity to create a national forum to establish the guidelines
      in this special branch of cardiology.

PMID- 7644824
TI  - [Rehabilitation in the heart transplant patient].
AB  - Cardiac transplantation should not only enlarge life time but additionally should
      provide the patient with good quality of life and a satisfactory rehabilitation
      level. An integrated rehabilitation program can help to the process of recovery.
      In spite of the multiple factors which modify the physiological response during
      exercise, an appropriate training can be reached by many patients. Nevertheless
      the physiological rehabilitation is one of the components of the patients global
      restitution in order to reach satisfactory life style after transplantation.

PMID- 7644825
TI  - [Rehabilitation in chronic heart failure].
AB  - The functional capacity of patients with chronic heart failure usually undergoes
      significant deterioration. Its decrease can be influenced by a low cardiac
      output, but is directly related to alterations at the level of the skeletal
      muscle. Cardiac rehabilitation programmes, which are therapeutic systems of
      multifactorial action (physical and psychological training, and guidelines for
      control of risk factors), have shown great benefits in this type of patients.
      There is an increase in the aerobic capacity, anaerobic threshold, O2 peak,
      cardiac out put and in the maximum O2 arteriovenous difference. This entails an
      improvement in functional capacity, which has a very positive influence on the
      psychological sphere. In view of the small number of cases included in the
      studies published, it is impossible to get to know the results at a prognosis
      level. The performance of physical training, which has to be carefully
      programmed, does not occasion more complications than when performed by low risk
      groups. There is no evidence proving that physical training deteriorates the
      ventricular function. The decrease in the ejection fraction found in some
      patients with very low values at the beginning of the programme could be
      secondary to other usual factors responsible for the negative evolution of this
      type of pathology.

PMID- 7644826
TI  - [Cardiac rehabilitation results at the physical, psychological, sexual and work
      levels].
AB  - Nowadays, the finality of the cardiac rehabilitation programs (CR) is
      fundamentally directed to improve the patient's life quality, connected to the
      functional capacity increase, symptoms improvement, psychological stability and
      correct social and labour reintegration. Physically, it is showed that CR
      programs increase the total effort capacity, decrease the HR and BP figures for a
      fixed submaximum effort level and decrease or eliminate the symptomatology, on
      myocardial ischemia cases, on cardiac insufficiency cases and on peripheral
      arterial disease. The physical improvement produce improvement at a psychological
      level, reflected on a physical and sexual self-esteem, depressive humor
      improvement, labour stress and on the participation on leisure and sexual
      activity. Physical and psychological comfort it is going to be a good support
      facing to the labour reintegration, although it will depend on the intellectual
      and study level, social status and family economical situation.

PMID- 7644827
TI  - [The effects of physical training].
AB  - Regular practice of dynamic physical exercise produces cardiovascular,
      metabolical, biochemical, hematological and endocrine changes among the most
      important ones. To reach the majority of these effects, it is not necessary to
      perform particularly intense training. The equivalent to one hour of active
      walking per day would be sufficient. However, the improvement of the physical
      condition is only achieved with specific training programmes. Changes originated
      by training are due to the effects of the actual exercise and to the
      modifications of the cardiovascular risk factors. Apart from this, the
      repercussion of regular physical exercise on conduct and personality should not
      be underestimated. Physical exercise is a complementary treatment measure which
      turns out to be the more efficacious the best prevention measures and
      conventional treatments are complied with.

PMID- 7644828
TI  - [Cardiac rehabilitation and secondary prevention in ischemic cardiopathy].
AB  - The experience gathered in the last thirty years has proved that cardiac
      rehabilitation improves the quality of life of the patients and contributes to
      their early return to work. As it consists in therapeutic systems of
      multifactorial action (physical training, psychological guidelines and control of
      risk factors), it can exert a positive influence on the prognosis through each of
      those actions or their sum. Despite the difficulties in the analysis of these
      programmes (need for a large number of patients and long follow-up periods), some
      studies and meta-analysis have proved that the incidence of complications and the
      mortality rate decrease in rehabilitated patients. Mortality goes down by 20-25%
      which is similar to the results obtained with perfectly accepted therapies, such
      a beta-blocking treatment, with the advantage that cardiac rehabilitation is
      cheaper and produces fewer side-effects. It goes without saying that these
      systems of prognosis action are complementary in a large number of patients.

PMID- 7644829
TI  - [An analysis of the quality of life of rehabilitated patients].
AB  - The improvement of the survival of cardiac patients may cause an impairment of
      their quality of life. At present, the study of the quality of life of the
      patients and its changes, must be considered as one of the aims of the Medicine.
      This study must be comprised clinical, functional, intellectual, social, and
      labor aspects, and all the items related to the environment of the patient. The
      first questionnaires used for the study of quality of life were generic but later
      on, specific questionnaires for different pathologies were found to be
      preferential. At present, there are questionnaires for hypertensive, myocardial
      infarction, angina and heart failure patients, and among them the questionnaire
      for myocardial infarction patients, structures and validated by the authors which
      has been used to study the quality of life postinfarction patients who followed a
      cardiac rehabilitation programme.

PMID- 7644830
TI  - [The cost-benefit of cardiac rehabilitation programs].
AB  - In the past 20 years there has been a steady improvement in the short-term
      prognosis of patients with myocardial infarction, following the introduction of
      beta blockers, thrombolysis, and aspirin. Cardiac rehabilitation and secondary
      prevention also has contributed to this improvement. However, the development
      cardiac rehabilitation is limited and not fully developed in Europe. Multiple
      reasons are related to the underuse of rehabilitation, between then the increase
      of economical cost associated rehabilitation services. The participation in
      comprehensive cardiac rehabilitation show and lower cardiac rehospitalization
      costs. Also, earlier return to work and less pension cost in patients included in
      cardiac rehabilitation. Several studies had confirmed rehabilitation programs are
      more cost-effective, in QALYs terms, that some drugs. Then, cardiac
      rehabilitation is an efficient health-care resource, and may be economically
      justified.

PMID- 7644831
TI  - The effects of visual and auditory models on the learning of a rhythmical
      synchronization dance skill.
AB  - The purpose of this study was to investigate the effect of visual and auditory
      concurrent models on the acquisition of a rhythmical synchronization task.
      Subjects attempted to synchronize a series of dance steps to the beat of two
      auditory rhythms. Subjects performed five trial blocks in one of four practice
      conditions: (a) audio-visual (auditory rhythms combined with a visual model), (b)
      audio-auditory (auditory rhythms combined with an auditory model), (c) auditory
      only (auditory rhythms with no model), and (d) visual only (no auditory rhythms
      but exposure to a visual model). Rhythmical timing and synchronization accuracy
      served as the dependent variables. Results revealed no practice condition
      learning differences for rhythmical timing. For synchronization accuracy, the
      audio-auditory group produced significantly lower error scores at acquisition,
      but no differences were found at retention. Apparently, the availability of
      models created an information dependency that resulted in a decrease of
      performance and, consequently, no group differences in retention.

PMID- 7644832
TI  - Examining the personal experience of student skill learning: a narrative
      perspective.
AB  - Examining the meaning of student skill learning from the learner's perspective is
      a valued but understudied topic in physical education. This paper investigated
      the learner's perspective as a storied experience and used narrative theory to
      interpret the meanings students derived from their learning experiences. Four
      narrative accounts were presented involving university students enrolled in a
      beginning level bowling class. The narratives centered on describing student
      goals and the conflicts and resolution of conflicts experienced by these students
      during skill learning. Two sources of generating meaning from experience were
      delineated: (a) an individual's active construction of meaning and (b) the
      enculturing influence of the social context. These narratives provided an
      opportunity for teachers and researchers to examine the realities constructed by
      students as a result of their learning experiences.

PMID- 7644833
TI  - The role of proletarianization in physical education teacher attrition.
AB  - As the quality of education provisions continues to come under scrutiny, so too
      have the conditions for teachers' work. The purpose of this study was to
      ascertain what were the dissatisfactions for beginning physical education
      teachers in Australian schools. Qualitative data were collected using interviews,
      journals, photographs, and field notes. Data yielded five main categories
      underpinning teacher dissatisfaction: (a) lack of status, (b) repetitive nature
      of physical education work, (c) limited decision making, (d) personal and
      professional surveillance, and (e) unprofessional staffroom culture. The
      construct of proletarianization was employed to explain the patterns that shape
      teachers' occupational socialization and underpin teachers' decisions to leave
      the profession.

PMID- 7644834
TI  - Attentional strategy use by experienced distance runners: physiological and
      psychological effects.
AB  - The purpose of this investigation was twofold: (a) to compare most and least
      economical runners on use of attentional strategies and (b) to determine whether
      the least economical runners within the subject sample could improve running
      economy (RE) with the use of an active associative (relaxation) attentional
      strategy. Subjects (N = 36) completed an initial assessment of attentional style
      and RE; then the 12 least economical runners ran in each of three laboratory
      sessions using control, passive associative, and active associative attentional
      strategies. Results showed that the most economical and least economical runners
      did not differ in associative style use. The most economical runners, however,
      reported less dissociation use and more use of relaxation than did the least
      economical runners. No significant physiological or psychological changes were
      associated with any of the three attentional strategy conditions. The findings
      are related to possible differences in how most and least economical runners use
      associative strategies.

PMID- 7644835
TI  - "I have a soul that dances like Tina Turner, but my body can't": physical
      activity and women with mobility impairments.
AB  - The purpose of this study was to explore the experiences and meanings of physical
      activity for women with disabilities and to interpret the implications of
      physical activities specifically for women with mobility impairments. In-depth
      qualitative interviews were used to uncover data about how women with mobility
      impairments experienced physical activity and leisure. Emerging themes addressed
      the value of physical activity, attitudes toward one's disability and
      participation in physical activity, and conditions necessary for involvement in
      physical activity. Four values were associated with physical activities: leisure,
      therapy, maintenance, or perceived little value. Attitudes toward one's
      disability and physical activity resulted in conforming, resisting, or adjusting
      behavior. Energy/stamina/low pain level, transportation, removal of social fears,
      accessibility, and social support were the individual or combined conditions that
      influenced values and attitudes regarding physical activities. The results of
      this study highlighted the need to consider and improve opportunities for
      physical activity for women with mobility impairments.

PMID- 7644836
TI  - A new technology and field test of advance cue usage in volleyball.

PMID- 7644837
TI  - Predicting muscular strength in women: a preliminary study.

PMID- 7644838
TI  - Multi-sample confirmatory factor analysis of the Task and Ego Orientation in
      Sport Questionnaire.
AB  - The Task and Ego Orientation in Sport Questionnaire (TEOSQ; Duda, 1989; Duda &
      Nicholls, 1992) was designed to assess individual differences in the proneness
      for task and ego involvement in athletic settings. The purpose of this study was
      to independently and simultaneously test the measurement model assumed to
      underlie the TEOSQ across intercollegiate athletes (n = 143), college students
      enrolled in skill classes (n = 270), high school athletes (n = 310), and junior
      high school sport participants (n = 234). Single-sample confirmatory factor
      analysis (CFA) was employed to establish and to evaluate the tenability of a
      baseline model in terms of each sample. A series of multi-sample CFAs were then
      conducted to test the invariance of the measurement and factor structure of the
      TEOSQ across the four groups. The measures of overall fit for the hypothetical
      two-factor structure of the TEOSQ were generally acceptable, albeit weaker in the
      case of the college students. Further, the results of the multi-sample CFA did
      not support the assumption for intergroup invariance of the TEOSQ. This finding
      indicated that the 13 items and structure of the TEOSQ were not equally valid
      across the present four samples.

PMID- 7644839
TI  - Using bandwidth knowledge of results to alter relative frequencies during motor
      skill acquisition.
AB  - This investigation examined the predictions of the guidance and specificity
      hypotheses by manipulating different distributions of relative frequency of
      knowledge of results (KR) using bandwidth (BW) conditions. Subjects (N = 120)
      were randomly assigned to either a BW0%, BW10%, Shrinking-BW, or Expanding-BW
      condition. After 100 acquisition trials were completed, a double transfer design
      was employed in which the subjects were divided in half and randomly assigned to
      a no-KR or KR retention condition. Retention tests of 10 min and 48 hr were
      completed under a no-KR or KR retention condition. Results of the 48-hr retention
      test under the no-KR retention condition suggested that receiving high relative
      frequencies of KR at the end of the acquisition phase was as detrimental to motor
      skill learning as receiving high relative frequencies of KR throughout
      acquisition. The results are discussed with respect to the guidance and
      specificity hypotheses.

PMID- 7644840
TI  - Ossiculoplasty with J.B. Causse composite prostheses: our experience with 500
      cases.
AB  - In ossicular pathology, many options are available when the restoration of the
      columellar effect is required. Autoplasty, heteroplasty and homoplasty have
      advantages and disadvantages, but considerable recent progress in development of
      the prosthesis has changed the state of the situation. 500 partial and total
      prostheses (Porp and Torp) of composite material (Flex HA and Teflon HA) designed
      by Jean-Bernard Causse and developed by Microtek, were used from January 1992
      until December 1993. The authors present results at short and middle term
      involving all aspects of otologic surgery, as well as surgical techniques that
      were used.

PMID- 7644841
TI  - Canal wall prosthesis--new devices.
AB  - In our experience, management of the troublesome mastoid cavity a
      "rehabilitation" of the middle ear, usually involves post canal wall
      reconstruction. The purpose of the long canal wall reconstruction is to restore
      the anatomy as perfectly as possible in order to induce satisfactory wound
      healing of both epidermal a mucosal layers. The numerous materials and different
      surgical procedures to date, demonstrate the difficulty of reconstruction of the
      ear canal. Over twenty years we have performed 386 cases using various materials:
      cortical bone, ear canal allograft, ceravital, porous and dense hydroxylapatite.
      More recently to improve the anatomical results we have used a new titanium
      prosthesis. The pros and cons of each device are discussed.

PMID- 7644842
TI  - Three-dimensional investigation of the postoperative condition after
      ossiculoplasty with hydroxylapatite corp. (Running title; 3-D investigation of
      Corp).
AB  - From January 1985 to December 1993, at Oita Medical University, we have employed
      hydroxylapatite ceramic ossicular replacement prosthesis (Corp) for 42
      ossiculoplasties for chronic otitis media with and without cholesteatoma and
      investigated the relationship between 3-dimensional condition of the prosthesis
      and hearing improvement after surgery according to the method of 3-D
      reconstruction technique as previously reported. The images of the middle ear and
      inner ear structures were traced on 4 or 6 tomograms of 2 mm thick slices from
      frontal view and input into the Nexus 6800 image processor. The 3-D images were
      reconstructed by using a 3-D reconstruction microsoft, TRI. The postoperative
      hearing improvement in ossiculoplasty with Corp was achieved in 23 (55%) of 42
      ears. In 28 (67%) of 42 ears, Corp was found to be in the proper position on
      tomograms and to tilt upwards in 10 years (24%) and downwards in 3 ears (7%). In
      one case, the prosthesis was rejected through the tympanic membrane 23 days after
      surgery because the head of Corp was not covered with cartilage plate. In 19
      (67%) of 28 ears, satisfactory hearing improvement was achieved, and Corp was
      well fitted to the tympanic membrane out of touch with other surrounding
      structures and vertical to the tympanic membrane, 3-dimensionally. In contrast,
      in 9 ears (33%) without improved hearing, the prosthesis was fixed in the proper
      position on the frontal plain, but it sifted backwards or forwards in 3-D
      reconstructed images.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7644843
TI  - The effect on tinnitus of stapes surgery for otosclerosis.
AB  - Among 42 Japanese patients with otosclerosis who underwent stapes surgery, 22
      patients including 10 received total stapedectomy, 6 partial stapedectomy and 6
      stapedectomy, were investigated on preoperative and postoperative tinnitus by
      sending questionnaire. The tinnitus was evaluated by "tinnitus score" advocated
      by the Japan Audiological Society, and the changes of the scores were analyzed
      according to pre- and postoperative hearing change, type of stapes surgery and
      pitches of preoperative tinnitus. In these 22 patients, tinnitus score was
      improved in 68%, unchanged in 27% or worsened in 5%. Tinnitus was completely
      disappeared in 6 patients or 27.3%. Tinnitus score became more markedly improved
      in the patients received partial stapedectomy or stapedotomy than those who
      received total stapedectomy. Tinnitus score was more likely improved in the
      patients who had a low pitched tinnitus and presumably had no cochlear
      otosclerosis preoperatively.

PMID- 7644844
TI  - [Surgical treatment of vertigo induced by jugular bulb diverticulum].
AB  - The position of the jugular bulb is extremely variable. A high jugular fossa with
      a diverticulum of the jugular bulb can alter the inner ear function with
      sensorineural hearing loss, vertigo and tinnitus. Nine cases of jugular bulb
      diverticulum with vertigo mimicking Meniere's disease were operated on and
      followed up from 3 months to 4 years. Eight patients were treated surgically. The
      jugular bulb was approached through a mastoidectomy and the diverticulum was
      compressed downwards using bone wax. The vertigo disappeared after surgery in all
      cases. These observations suggest that an abnormally of the jugular bulb should
      be considered as a possible symptom of Meniere's disease and that vertigo can be
      cured by downward compression of the diverticulum.

PMID- 7644845
TI  - Rehabilitation of long-term facial paralysis.
AB  - A wide variety or techniques have been developed over the years in an effort to
      reduce the devastating impact of facial paralysis on the patient. The authors
      choose to perform hypoglossal-facial nerve anastomosis when facial facial nerve
      anastomosis, or cross-over, or microvascular muscle transplantation are
      impossible. Nevertheless, these results appear always insufficient for palpebral
      occlusion. The authors propose to associate two rehabilitation technique to
      obtain optimal results. They perform hypoglossal facial nerve anastomosis using
      the technique modified by U. Fisch, and they associate temporal muscular transfer
      to improve ocular protection. This association imposes an increased strain on the
      patient in an effort to undertake double re-education which modifies twice his
      classic corporeal scheme. The surgical technique are associated after evaluation
      of the possibility of the patient adherence to the long duration physical
      therapy.

PMID- 7644846
TI  - [Sonomotor vestibular reflex in acoustic neuroma].
AB  - Despite recent advance in diagnosis and surgical techniques of acoustic neuroma,
      ideal criteria for hearing preservation attempt remain unsatisfactory. This study
      reports sonomotor vestibular reflex recorded pre and postoperatively in 20
      patients with acoustic neuroma. Hearing preservation was attempted according to
      tumor size and preoperative pure tone audiometry results. The studied population
      was divided in 2 groups according to hearing preservation was attempted (group 1
      n = 13, retrosigmoid approach) or not (group 2 n = 7, translabyrinthin approach).
      In accordance with postsurgical audition, the subjects of group 1 were
      distributed in group 1-A (postsurgical preserved audition n = 4) or group 1-B
      (postsurgical unpreserved audition n = 9). Presurgical sonomotor vestibular
      reflex in response to pathological stimulation were compared in the different
      groups. In preoperative period, sonomotor vertibular reflex in response to
      pathological side stimulation were present in all the patients of group 1-A with
      a similar amplitude to those obtained when stimulating healthy side. In 6
      subjects of group 1-B these responses were present but with a smaller amplitude
      than those obtained when stimulating healthy side. The responses were absent in 3
      subjects of group 1-B and in all the subjects of the group 2. These result tend
      to demonstrate that preoperative presence of sonomotor vestibular reflex in
      response to neuroma side stimulation with amplitude similar to those obtained by
      healthy side stimulation is a favorable criterion for hearing preservation
      attempt. On the opposite, the decrease in the amplitude of these responses or
      their absence seems to be unfavorable for hearing preservation attempt.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7644847
TI  - [Biomechanics of the middle ear].
AB  - We describe the main biomechanical characteristics of the middle ear in man and
      in animals. Physical principles of functionment, tympano-ossicular displacements,
      acoustic reflex, adaptation of impedance, transfer function of the middle ear,
      middle ear as an acoustic power transformer... are presented. Practical
      consequences for the hearing sensitivity, the susceptibility to noise and some
      clinical applications are discussed.

PMID- 7644848
TI  - [Tubo-petrous fistula with valve: apropos of a case].
AB  - The abnormal pneumatization of the apex of the petrous bone may determine
      pathological disturbances in the existing conditions of a tube-petrous fistula
      with valve. Such a clinical case is presented with tube-petrous fistula, which
      during a period of four years was investigated in several clinics due to its non
      typical clinical symptoms, without the diagnostic or treatment having been
      mentioned. The authors insisted that the Eustachian tube should be investigated
      in order to establish a probable diagnostic. The paper presents the technique of
      operation used, the injuries found and the manner of obturating the fistula in
      two successive surgical operations.

PMID- 7644849
TI  - The Hong Kong vascularized temporalis fascia flaps for optimal, mastoid cavity
      reconstruction.
AB  - The classical modified radical mastoidectomy offers the advantages of combining
      the mastoid cavity, the attic and the external canal into one cavity that remains
      open for inspection. However the ultimate goal to predictably produce well
      healed, dry and safe mastoid cavities despite receiving much attention has not
      been fulfilled. By employing basic surgical principles of wide access to
      facilitate meticulous removal of all cholesteatoma and then eliminating all raw
      surfaces of the bony cavity with pedicled vascularized deep temporalis fascia,
      the Hong Kong Flap technique achieves the highest percentage of dry, stable,
      disease free ears. This living fibrous tissue layer provides the optimal
      substrate for epithelial resurfacing while separating the mucosa and bone of the
      middle ear and mastoid from the surface epithelium. Excellent healing even under
      unfavourable circumstances is ensured by the rich blood supply to the pedicled
      temporalis fascia flap. Furthermore the technique obviates the need for second
      look procedures in more than two-thirds of cases as the cavity lining becomes
      transparent and simple observation is safe. The Hong Kong Flap was used to
      reconstruct 107 cavities between October 1988 and October 1992. 86 were performed
      for primary cholesteatoma removal and 21 for revision of discharging cavities.
      103 (96%) healed soundly. There were 4 dry perforations. Minor complications
      occurred in 8 (7%) patients. 84 (78%) required n+o second exploratory operation.
      This is a straight forward procedure requiring no special technical skills. The
      concept is rational and provides the ideal management for cholesteatoma by
      achieving a dry, safe ear with one operation.

PMID- 7644850
TI  - [Pathogenesis of cholesteatoma: contribution of otoscopic photography].
AB  - The filiation between otitis media with effusion, retraction pockets and
      cholesteatoma appears for most otologist to be very probable and logical but
      remains controversial. Some experts argue rigourously and they say fairly that it
      has not been so far strictly proven. Long term otoscopic observation supported by
      photography could bring indisputable evidences. During a 12 years period we have
      taken routinely otoscopic photography of every patient with chronic otitis media.
      We have been able to observe the appearance of cholesteatoma in ear apparently
      normal at the origin or which presented so-called simple chronic middle ear
      disease. We report some of the most characteristic observations.

PMID- 7644851
TI  - The use of Davis pinch grafts to promote epithelialization in a post-
      mastoidectomy cavity.
AB  - Otorrhoea following open mastoid cavity surgery is common and is estimated to
      occur in 10 to 35% of patients. It is usually due to failure of epithelialisation
      of the mastoid cavity for a variety of reasons. Even in the ideal cavity, which
      is small with a low facial ridge and large meatus, 10% discharge recurrently.
      Various techniques designed to promote epithelialisation have been proposed
      including cavity revision with or without a meatoplasty, cavity obliteration by
      different methods and partial or total reconstruction of the cavity. No single
      technique has proved superior. Other approaches that directly address the problem
      of epithelialisation have been used, including partial thickness skin grafting,
      autologous and indeed synthetic epidermal cell grafting, with varying degrees of
      success. We describe the Davis pinch graft technique, as devised by Holsted and
      popularized by Davis for venous ulcers. Free pinch grafts consisting of epidermis
      and small amounts of dermis are taken from the anterior abdominal wall and
      inserted into the revised mastoid cavity. We present a retrospective study of 15
      patients who underwent revision mastoidectomy and Davis pinch grafting for
      persistent ottorrhoea, and discuss the results with respect to patient
      symptomatology and the surgeons assessment of the cavity. In conclusion, we
      believe that the Davis pinch graft has a proven beneficial effect in the
      management of post-mastoidectomy otorrhoea.

PMID- 7644852
TI  - [Effects of buflomedil and naftidrofuryl on the human cochlear microcirculation
      measured by laser-Doppler].
AB  - The aim of this study was to assess the effects on cochlear blood flow measured
      by laser-Doppler of two vasoactive agents known for their supposed effectiveness
      in the presbyacousy treatment (buflomedil, naftidrofuryl), 16 patients undergoing
      acoustic neurinoma surgery were studied. Cochlear blood flow (CBF) was
      continuously recorded after the head of the probe was inserted into the internal
      ear through the round window. Systolic arterial pressure (SAP) and heart rate
      (HR) were continuously recorded via an arterial cannula. Hemodynamic variations
      due to buflomedil (400 mg in bolus) and to naftidrofuryl (200 mg in bolus) were
      compared with those of sodium nitroprusside (500 micrograms in bolus) in each
      case with anova. Buflomedil did not alter CBF (0%), SAP (+0.14 +/- 1.7%), HR
      (+3.4 +/- 3.4%). Naftidrofuryl provoked a significant decrease (P < 0.05) of CBF
      (-14.5 +/- 7.55%), SAP (-13.7 +/- 4%), and a significant increase (P < 0.05) of
      HR (+8.5 +/- 3.5%); there is a relationship between CBF and SAP (r = 0.88 P <
      0.05). NPS provoked a significant decrease (P < 0.01) of CBF (-34.7 +/- 7.7%) SAP
      (-26.8 +/- 5.4%) and a significant increase (P < 0.01) of HR(+14.7 +/- 7.3%) in
      the same way of naftidrofuryl (P < 0.01). In conclusion, human cochlear
      microcirculation depends upon pharmacological hemodynamic variations such as
      animal models or middle ear microcirculation. If buflomedil did not alter it,
      naftidrofuryl provoked a reduction by a direct vasodilator effect inducing
      hypotension like sodium nitroprusside.

PMID- 7644853
TI  - [Peroperative catheterization of the Eustachian tube].
AB  - Peroperative catheterization of the Eustachian tube is an exploratory and
      management technique enabling a better understanding of the pathological
      phenomena, resulting in a more effective therapeutic orientation for short term
      lesions (infection). In the long term, tubal rehabilitation becomes a logical
      complement.

PMID- 7644854
TI  - Statistical issues in assessing comorbidity.
AB  - I define three separate and distinct types of non-random comorbidity:
      epidemiologic, clinical and familial. These might exist singly or in any
      combination for a pair of disorders. The focus is on their definition and the
      measurement and interpretation of the types of comorbidity of most common
      concern: epidemiologic comorbidity. I discuss certain sources of epidemiologic
      comorbidity such as shared risk factors, or diagnostic 'fuzziness', and I
      indicate the directions of research design and analyses to disclose such sources.

PMID- 7644855
TI  - Model inconsistency, illustrated by the Cox proportional hazards model.
AB  - We consider problems involving the comparison of two or more treatments where we
      have the opportunity to adjust for relevant covariates either conditionally in a
      regression model or implicitly in repeated measures data, for example, in
      crossover trials. It is seen that for data arising from non-Normal distributions
      there is the possibility that models adjusting for covariates and those not
      adjusting for covariates will be inconsistent, that is, at most one of the models
      can be valid. Alternatively, even if conditional and unconditional models are
      valid, parameters in each model may have different interpretations. We note that
      this presents difficulties for the specification and interpretation of the
      analysis. It is also clear that model validation is critical. Specific attention
      is paid to survival data analysed by the Cox proportional hazards model.

PMID- 7644856
TI  - The analysis of repeated-measures data on schizophrenic reaction times using
      mixture models.
AB  - Reaction times for schizophrenic individuals in a simple visual tracking
      experiment can be substantially more variable than for non-schizophrenic
      individuals. Current psychological theory suggests that at least some of this
      extra variability arises from an attentional lapse that delays some, but not all,
      of each schizophrenic's reaction times. Based on this theory, we pursue models in
      which measurements from non-schizophrenics arise from a normal linear model with
      a separate mean for each individual, whereas measurements from schizophrenics
      arise from a mixture of (i) a component analogous to the distribution of response
      times for non-schizophrenics and (ii) a mean-shifted component. We fit four
      mixture models within this framework, where the distinctions between models arise
      from assumptions about the variance of the shifted observations and the
      exchangeability of schizophrenic individuals. Some of these models can be fit by
      maximum likelihood using the EM algorithm, and all can be fit using the ECM
      algorithm, where the covariance matrices associated with the parameters are
      calculated by the SEM and SECM algorithms, respectively. Bayesian model
      monitoring using posterior predictive checks is invoked to discard models that
      fail to reproduce certain observed features of the data and to stimulate the
      development of better models.

PMID- 7644857
TI  - Logistic regression in case-control studies: the effect of using independent as
      dependent variables.
AB  - In case-control studies, cases are sampled separately from controls. In such
      studies the primary analysis concerns the estimation of the effect of covariables
      on being a case or a control. To explore causal pathways, further secondary
      analysis could concern the relationships among the covariables. In this paper the
      validity of such secondary analysis is addressed. In particular, the use of
      multiple logistic regression in case-control studies where the dependent variable
      is not the case/control indicator is explored. It is shown that only under very
      restrictive conditions will sample regression coefficients correctly estimate
      their true value. In many situations, it may be valid to regress one covariable
      on others in the control group, but not in the case group or the combined sample.
      This principle is illustrated by a study of sexually transmitted disease in
      Kenya.

PMID- 7644858
TI  - Percentile regression analysis of correlated antibody responses.
AB  - Antibody responses following vaccination usually are analysed by comparing
      geometric mean concentrations across levels of relevant covariates and by
      comparing the proportions of vaccinees responding. In the regression setting, the
      analyses are done on log-transformed concentrations, estimating geometric mean
      responses conditional on a vector of covariates. More detailed analyses examining
      the relationship of covariates to different parts of the response distribution
      may be performed through the application of asymmetric least squares estimation
      of regression percentiles. We present a method for accounting for correlation in
      percentile regression analyses of longitudinal antibody response data. We
      illustrate the procedures with measles antibody response data from Haitian
      children who participated in a randomized trial of high titre vaccines. The
      strongest dose and strain effects were seen in the low end of the antibody
      concentration distributions.

PMID- 7644859
TI  - Effects of correlated and uncorrelated measurement error on linear regression and
      correlation in medical method comparison studies.
AB  - It is well known that when uncorrelated measurement error affects both variables
      in linear regression, there is attenuation of the correlation coefficient and
      regression slope. The effect of correlated measurement error, however, has
      received little attention. In medical method comparison studies, such error
      correlation results from the presence of other, unknown explanatory variables
      that affect the results of the new test method and the reference test method to
      which it is being compared. The contribution of correlated measurement error to
      the observed correlation coefficient can be accounted for by the expression rho
      t1t2 = rho1 rho2 + rho E1E2 (1-rho2(1))1/2(1-rho 2(2))1/2 where rho t1t2 is the
      observed correlation between tests 1 and 2, rho 1 and rho 2 are the correlation
      with true values for tests 1 and 2, respectively, and rho E1E2 is the correlation
      between the test errors. The first term describes the attenuation due to
      uncorrelated error, the second term describes the effect of correlated error. A
      positive correlation between the measurement errors reduces the attenuation of
      observed correlation and slope, but, when the reference method is excellent, the
      effect is very small. For poorer reference tests whose correlations with true
      values are less than 0.9, however, error correlation may result in a slope and
      correlation coefficient that differ importantly from the values obtained with
      either uncorrelated error or with no reference test error. Negatively correlated
      measurement errors magnify the attenuation of slope and correlation. One might
      suspect the presence of correlated error when the observed regression slope is
      close to or exceeds 1 and the reference test is known to have suboptimal
      reliability. This paper provides several clinical examples of potentially
      correlated diagnostic methods.

PMID- 7644860
TI  - Spatial disease clusters: detection and inference.
AB  - We present a new method of detection and inference for spatial clusters of a
      disease. To avoid ad hoc procedures to test for clustering, we have a clearly
      defined alternative hypothesis and our test statistic is based on the likelihood
      ratio. The proposed test can detect clusters of any size, located anywhere in the
      study region. It is not restricted to clusters that conform to predefined
      administrative or political borders. The test can be used for spatially
      aggregated data as well as when exact geographic co-ordinates are known for each
      individual. We illustrate the method on a data set describing the occurrence of
      leukaemia in Upstate New York.

PMID- 7644861
TI  - The log transformation is special.
AB  - The logarithmic (log) transformation is a simple yet controversial step in the
      analysis of positive continuous data measured on an interval scale. Situations
      where a log transformation is indicated will be reviewed. This paper contends
      that the log transformation should not be classed with other transformations as
      it has particular advantages. Problems with using the data themselves to decide
      whether or not to transform will be discussed. It is recommended that log
      transformed analyses should frequently be preferred to untransformed analyses and
      that careful consideration should be given to use of a log transformation at the
      protocol design stage.

PMID- 7644862
TI  - Trends in mortality from melanoma in Canada and prediction of future rates.
AB  - A long term increase in incidence of and mortality due to malignant melanoma has
      been observed in all well documented white populations. The major identified
      cause of melanoma is sun exposure. One would expect predictions of future
      atmospheric ozone depletion to lead to an increase in ultraviolet radiation (UVR)
      and in the effects of sun exposure. We consider age-period data for Canadian
      malignant malanoma mortality. We fit a multiplicative exponential/logistic (MEL)
      model to the data and extrapolate to AD 2010 hence yielding point estimates of
      future rates. We obtain total mortality forecasts by multiplying rates by
      population estimates. We present standard errors for forecasts. We forecast that
      melanoma will be a much larger burden on the health care system in the early
      years of the next century than it is at present. We obtain an age-cohort model by
      a simple transformation of the age-period model. Also, we obtain unconditional
      probabilities of death due to melanoma both for age-period and age-cohort models.
      We discuss the assumptions underlying the MEL model that suggest possible
      relationships between UVR and melanoma.

PMID- 7644863
TI  - An alternative approach to the optimal design of an LD50 bioassay.
AB  - In this paper we propose an alternative approach to the optimal design of an LD50
      bioassay. We adopt a Bayesian approach to make use of prior information about the
      location and scale parameters of the tolerance distribution function to select
      the design parameters (number of doses, total number of animals, centre of doses,
      space between doses), and we adopt a frequentist approach using the Spearman
      Karber statistic to estimate the LD50. We define the optimal design as the one
      that produces the minimum expected mean squared error E(MSE) with respect to the
      joint prior distribution of the parameters of the tolerance distribution. For the
      design parameters investigated, we found: (i) the shape of the E(MSE) is
      relatively smooth and continuous, the magnitude of which is influenced by the
      underlying tolerance distribution; (ii) the amount of prior information about the
      location and scale parameters independently and jointly affect the optimal
      design; and (iii) as the amount of prior information decreases, one requires more
      doses and/or animals. Finally, we show the proposed method is robust for an
      incorrectly assumed tolerance distribution function.

PMID- 7644864
TI  - Bias of two one-sided tests procedures in assessment of bioequivalence.
AB  - The current applications of Schuirmann's two one-sided tests procedure for the
      original scale ignore the variability of the least squares mean of the reference
      formulation when it substitutes for the unknown reference average of
      pharmacokinetic responses. We propose a modified two one-sided test procedure
      that takes into account the variability of the least squares mean of the
      reference formulation. The non-parametric version of the modified procedure is
      also available. We conducted a simulation study to examine the true level of
      significance and empirical power of four current parametric and non-parametric
      two one-sided tests procedures under a 2 x 2 crossover design with different
      combinations of sample size, intrasubject variability, and correlation between
      the two responses from a subject. Both theoretical results and empirical evidence
      show that the true level of significance of the current two one-sided tests
      procedures converges to 0.5 when the correlation of the two responses approaches
      1. However, not only is the modified two one-sided tests procedure a test of size
      alpha, but empirical evidence indicates it is also an unbiased test. The modified
      non-parametric procedure also controls the size of the tests and is competitive
      even under normality assumption.

PMID- 7644865
TI  - A comparison of tests for the k-sample, non-decreasing alternative.
AB  - This paper compares, by means of Monte Carlo simulations, three non-parametric
      tests to detect a non-decreasing trend in location parameters. The three tests
      are the Jonckheere-Terpstra test, the Cuzick test, and the Le test. We estimated
      power for each test across a wide variety of non-decreasing location parameters
      under four different types of distributions. None of the tests produced an
      overwhelmingly higher power over their two competitors.

PMID- 7644867
TI  - [Maternal prognostic factors in severe eclampsia].
AB  - Sixty cases of severe eclampsia were treated in an intensive care unit between
      January 1989 and September 1993. Mean age was 26, and 70% of patients were
      primipara. The pregnancy has been unsupervised in almost all cases. All had
      visceral lesions and/or hematologic problems and there was impaired conscious
      level in 9 cases out of 10. Medical treatment involved the control of seizures
      and of hypertension. Cesarean section was performed in 34 cases. The maternal
      death rate was 23.3%. Our experience indicates that mortality depends upon
      visceral lesions (cerebral, disseminated intravascular coagulation, acute
      pulmonary edema, Hellp syndrome). Better awareness of severity factors in
      preeclampsia improves both maternal and fetal prognosis by precisely indicating
      the best time for fetal extraction.

PMID- 7644866
TI  - [Anatomic findings during 509 microscopic sphincteroplasties for urinary stress
      incontinence in women. Diagnostic and surgical consequences].
AB  - Stress incontinence of urine without cervicocystoptosis secondary to difficult
      labor and delivery is essentially due to rupture of the smooth muscle sphincter
      of the bladder. Other changes affecting the anterior vaginal wall (thinning of
      fibrous tissue, partial splitting of the striated urethral sphincter, etc.) are
      found before difficult labor without stress incontinence of urine. Only operative
      microscopy enables anatomical analysis. Lateral cystography confirms the clinical
      diagnosis. There is no correlation between the extent of lesions and functional
      study results. Surgery is limited to the dissection and apposition of the
      residual zone of the smooth muscle sphincter retracted laterally. There were
      neither postoperative dysuria nor dyspareunia. There were 11 recurrences. No
      marked symptomatic change 5 years later.

PMID- 7644868
TI  - [Uterine rupture: 50 cases].
AB  - The author reports 50 cases of rupture of the uterus among 11,060 labors i.e. one
      rupture per 220 labors. This study shows that rupture of the uterus occurs in
      women in poor socio-economic circumstances. Uterine scarring seems to be a more
      important factor than age and multiparity. Traumatic rupture is also common,
      resulting from obstetric procedures but above all from abdominal expression, most
      often performed outside hospital. Rupture of the uterus may present in many
      different ways. It was diagnosed in 32 cases before delivery while in 18 cases it
      was discovered during cesarean section or extraction of retained placenta. The
      lower segment was the elective site of rupture. With regard to treatment, suture
      was possible in 42 cases while hysterectomy proved necessary in the other 8 cases
      in view of the poor local tissue state. The prognosis remains gloomy, with a high
      risk of maternal death and, above all, a 58% fetal death rate.

PMID- 7644869
TI  - [Unrecognized hemorrhages during delivery].
AB  - On the basis of a series of 600 deliveries between January 1 and May 1 1993, the
      authors analyze cases of unrecognized delivery-related hemorrhage. Hemorrhage of
      this type, defined retrospectively on the basis of a difference of at least
      3g/100 ml in hemoglobin levels at the time of admission to the labor ward and on
      the 2nd day post-partum, were found in 3.83% of deliveries and were responsible
      for 51.11% of falls in hemoglobin of 3g/100 ml or more. Primiparity, induced
      labor (oxytocics), episiotomy, forceps extractions and cesarean section are their
      etiologic factors. Particular care should be taken in the presence of any of
      these factors and induced labor may be useful in the prophylaxis of these
      unrecognized hemorrhages.

PMID- 7644870
TI  - [Primary Bartholin gland cancer and etiopathogenetic role of human
      papillomavirus. Report of a new case].
AB  - The authors report a new case of Bartholin's gland carcinoma and its link with
      human papillomavirus. Should women with HPV have Pap smears the accessory glands
      of the vulva in addition to cervical smears?

PMID- 7644871
TI  - [A rare vaginal tumor: primary leiomyosarcoma. A case report].
AB  - Vaginal leiomyosarcoma is a very rare tumor. The authors report a case of primary
      presentation in a 51-year-old multipara who complained of the development, since
      about 12 months previously, of a vaginal swelling accompanied by bloody discharge
      and pain. The outcome was fatal twenty two months later following treatment
      combining chemotherapy, radiotherapy, and surgery. The case is discussed in the
      light of data from the literature.

PMID- 7644872
TI  - [Uterine rupture after twenty-two weeks of amenorrhea due to placenta praevia
      percreta. A case report].
AB  - The authors report a case of rupture of the uterus 22 weeks after the LMP, due to
      placenta praevia percreta and requiring emergency hysterectomy to arrest
      bleeding, followed by urinary complications. With the predisposing factors of the
      scars of 4 previous cesarean sections and the low anterior insertion of the
      placenta, this exceptional case--in terms of its rarity and gravity--led the
      authors to undertake a review of the literature seeking other cases of this
      greatly feared obstetric complication. They review the clinical, ultrasonographic
      (notably the use of color Doppler) and paraclinical (MRI, cystoscopy) diagnostic
      approach necessary to make an accurate diagnosis of placenta percreta (if
      possible before any hemorrhagic complications). This situation virtually
      invariably requires hysterectomy to arrest bleeding, under very difficult
      conditions because of the massive hemorrhage involved. Mortality remains high and
      morbidity principally concerns the urinary complications frequently encountered.

PMID- 7644873
TI  - [Pre-therapeutic management and surveillance of menopausal hormone replacement
      therapy].
AB  - Pre-therapeutic evaluation of menopausal hormone replacement therapy (HRT)
      requires certain measures in addition to a standard gynecological assessment. It
      is important to identify any possible breast or endometrial disorder which might
      require specific treatment or an adjustment of standard HRT. Skeletal status is
      assessed by history and, if necessary, by double-photon absorptiometry. Following
      such evaluation, absolute contra-indications are few in number, by virtue of the
      use of natural estradiol and non-androgenic progestogens. They essentially
      concern breast cancer and a thrombo-embolic history. The first follow-up visit,
      at three months, enables confirmation of the acceptability and efficacy of
      treatment and its adjustment if required. A monitoring calendar is then
      suggested.

PMID- 7644874
TI  - [Does balneology still have gynecologic indications?].
AB  - There are still some precise and traditional indications for the use of spa
      treatment in gynecology, even though they have been reduced or limited by the
      extraordinary progress made in exploratory techniques and different medico
      surgical treatments. It also appears that the most recent and varied of these
      indications, especially concerning the multiple problems linked to menopause, can
      be usefully treated by spa-therapy. It is the role of practitioners, well
      informed of the multiple treatments available in the centers of hydrotherapy, to
      make the right choice, at the right moment, and concerning the right spa-center.

PMID- 7644876
TI  - Aldo Spirito (1905-1992). The causes of tumoral transformation. A general theory.

PMID- 7644875
TI  - [Vascular anomalies: obstacles in ureteral dissection in centripetal radical
      surgery for uterine cancer].
AB  - Vascular abnormalities may create difficulties during exposure of the lateral
      surface of the ureter during radical lymphadeno-hystero-colpectomy for uterine
      carcinoma. The aim is to avoid peroperative bleeding due to damage to abnormal
      vessels (in particular abnormal anastomotic uterine vein) crossing the lateral
      surface of the ureter. The authors have encountered such vascular abnormalities
      three times during radical lymphadeno-hystero-colpectomy. Recognition of the
      abnormal vessel crossing the lateral surface of the ureter and its division
      between two separate sutures prevented accidental peroperative bleeding as well
      as possible damage to the terminal (juxta-vesical) part of the ureter.

PMID- 7644877
TI  - [Medical specialty teaching program in preventive medicine].

PMID- 7644878
TI  - [Economic assessment on medications: effects on pharmaceutical industry and
      health administration].
AB  - The present article discuss briefly the different methods of economic assessment
      of drugs, how and where the methods can be included alongside clinical trials,
      and discuss their influence in the pharmaceutical industry and health care
      administration. There are several methodological limitations when adding the
      economic assessment into a clinical trial principally because they differs in the
      aims. Economic assessment is interested in efficiency and clinical trials in
      security and efficacy. Pharmaceutical industry have been developing
      pharmacoeconomic departments in order to increase the internal efficiency of the
      viability of new products and to generate studies for regulatory authorities. At
      the moment, for regulatory purposes in Spain, an economic assessment is nor
      required but is recommended. The standardization of the methodology of the
      economic assessment is a key issue that may produce the spread and adoption in
      health care decision making process.

PMID- 7644879
TI  - [A critical analysis of the new Spanish regulation on immunological medications].
AB  - The Law on Medicaments warns in its article 39, of the existence of immunological
      medicaments in the context of the so called "special", adapting the Directive
      89/342/CEE to the Spanish Pharmaceutical Legislation. Under this perspective,
      immunological medicaments are regulated, adopting for that, the necessary
      measures to guarantee raw materials quality, and the necessary provisions are
      established for the observance of criteria on quality, reliability and efficiency
      of this kind of medicaments authorization, production and control. The most
      outstanding thing in the Royal Decree 288/91 of 8th March, is the faculty
      conferred to the Ministry of Health and Consumer Affairs to submit for previous
      authorization each lot of immunological medicaments before they are
      commercialized. Therefore, this is an innovatory Royal Decree regulating
      correctly this special kind of medicaments and collecting all tendencies dictated
      by the European Community.

PMID- 7644880
TI  - [Present regulation on infant and follow-on formula].
AB  - BACKGROUND: The commercialization of breast milk substitutes has had great
      economic transcendence, sometimes without considering the sanitary and
      nutritional consequences for the customer. The sanitary authorities have been
      implied in this matter both in the International and European fields, issuing
      standards and regulations for the commercialization of breast milk substitutes
      which have been adopted by the Spanish Regulation. The aim of this paper is
      comment the regulations that affect foods for breast-feeding and short age
      children. METHODS: This report analyzes and comments on the contents of
      international, european and national regulation on infant and follow-on formula.
      RESULTS: The regulations about Infant formula and Follow-on formula, banning the
      term of "humanized milk" and remarking the preference for breast feeding, which
      could only be substituted by sanitary professionals. This regulation deals with
      the appropriate chemical composition of these products, qualitative and
      quantitative. It includes standards for correct labeling, which should contain
      the appropriate information without idealizing the product Drawings and pictures
      showing the correct preparation are allowed. It provides for distribution and
      sales, as well as for correct advertising, which should be under control. This
      regulation also bans free samples and any other donation to particular customers
      or sanitary institutions. CONCLUSIONS: The present regulation on "Infant and
      Follow-on formulas" pursues the adequate nutrition of breast-feeding and short
      age children, being the protection of this kind of customers everyone's
      responsibility.

PMID- 7644881
TI  - [Comparison of deaths in the case register of AIDS and deaths of AIDS in
      mortality register: Barcelona 1991-1992].
AB  - BACKGROUND: To compare information on the deaths detected by the register of AIDS
      cases and the register of deaths due to AIDS in residents of Barcelona, with the
      objective to determine the differences between the two. METHODS: Mortality data
      were obtained from the register of AIDS cases and the mortality register during
      1991 and 1992. The two registers were linked and concordant cases were
      identified. RESULTS: During 1991-92 there were 582 deaths on the case-register
      and 525 on the mortality register. It was possible to link 458 cases. The 67
      cases not detected by the register of cases of AIDS were due to the fact that
      some had not been reported (35.9%), some were not AIDS cases (28.3%), some lacked
      information that qualified them as AIDS cases (28.3%), or were from a different
      residence (7.5%). The 124 cases that were not detected in the mortality register
      were due to their having another underlying cause of death (60.5%), a different
      residence (21.8%) and a lack of information since 22 deaths could not be
      identified in the mortality register, therefore, the cause of death could not be
      identified (17.7%). CONCLUSIONS: To do a correct epidemiological surveillance of
      AIDS, a good coordination between the case and the mortality register is
      necessary.

PMID- 7644882
TI  - [Rational structures in health education models: basics and systematization].
AB  - The different Health Education (HE) models appeared in the scientific literature
      are analyzed, trying to eliminate the confusion produced by its great diversity,
      applying a general and systematic point of view. Due to the relevance of that
      topic in the activities of Health Promotion in Primary Health Care it is urgent a
      deep reappraisal due the heterogeneity of scientific papers dealing with that
      topic. The curriculum, as the confluence of thought and action in Health
      Education, is the basic concept thanks to which it is possible to integrate both
      scientific logic, the biological one and that pertaining to the social sciences.
      Of particular importance have been the different paradigms that have emerged in
      the field of HE from the beginning of the present century: a first generation
      with a "normative" point of view, a second one orientated from positivistic
      bases, and a third generation adopting an hermeneutic and critic nature. This
      third generation of paradigms in HE has taken distances from the behaviouristic
      and cognitive perspectives being more critical and participative. The principal
      scientific contributors in the field of HE, internationals as well as spaniards
      are studied and classified. The main conclusions obtained from this Health
      Education paradigm controversy are referred to both aspects: 1) planning,
      programming and evaluating activities, and 2) models, qualitative and
      quantitative methodologies. Emphasis is given to the need of including Community
      Participation in all phases of the process in critic methodologies of HE. It is
      postulated the critic paradigm as the only one able to integrate the rest of the
      scientific approaches in Health Education.

PMID- 7644883
TI  - [Breast cancer prevention program in Valenciana community. Assessment 1992-1993].
AB  - BACKGROUND: In 1992, a breast cancer screening program was implemented by the
      General Directorate of Health of the Autonomous Government of Valencia. This
      program was aimed to decrease the mortality caused by breast cancer in a 30% on
      those women submitted to the program. The program was implemented, in 1992 and
      1993, and with this purpose five units of breast cancer screening were set up in
      five Health Areas. This paper presents our preliminary results of this program,
      from april 1992 to december 1993. METHODS: The program target population
      consisted on 125,000 healthy women aged from 45 to 65 years. Each woman
      recruited, a two-view (cranio-caudal and medio-lateral oblique) screen-film
      mammograms were performed as the primary and only film-screening examination with
      two years interval. Additionally and according to the criteria of the physician
      charged to inform the mammography a physical examination could be practised.
      RESULTS: 52,843 women were invited to participate. The participation rate was of
      70.78%. The number of breast cancer detected was of 141, corresponding to a rate
      of 3.90/1000 women under screening program. CONCLUSIONS: The objectives stated,
      in relation to participation rate, methods applied and early time of detection,
      were achieved in this period of assessment.

PMID- 7644884
TI  - [Analysis of the efficiency of the screening of anti-HVA IgG antibodies before
      active or passive immunization].
AB  - BACKGROUND: The epidemiological patron of hepatitis A has changed in the last few
      years and a decrease of the anti-hepatitis A antibodies IgG (Anti-HVA) have been
      observed at early ages, which will accompany in the future an increase of
      symptomatic hepatitis. The prevention of hepatitis A requires a strict
      application of the norms of personal and environmental hygiene and the
      administration of vaccines or immunoglobulins. In order to determine the
      convenience of immunization actively or passively with or without the previous
      detection of Anti-HVA, requires the knowledge of with strategy is more efficient.
      METHODS: An analysis is carried out to determine the threshold of prevalence,
      where the reason of efficiency is established by comparing the unit cost of
      immunization either actively or passively of the population, with a cost of
      immunizing only the negative Anti-HVA by previous screening, with the formula:
      the unit cost of the active or passive immunization (unit cost of screening +
      cost of active or passive (in specific immunoglobuline) immunization in the
      negative Anti-HVA). The results correlate with the prevalence of Anti-HVA in age
      group founded in sero-epidemiological studies published by Salleras (1992 and
      Perez-Trallero (1994). RESULTS: The threshold of prevalence, the reason of
      efficiency equals 1, it's situated in 18% and 65% respectively for the active and
      passive immunization, which corresponds to the age group of 10-19 years and 20-29
      years based on sero-epidemiological studies used. CONCLUSIONS: With prevalence of
      Anti-HVA equal to or above 18% of the population the most efficient strategy is
      to determine the Anti-HVA before the active immunization; This threshold of
      prevalence move to up to 65% with passive immunization. Beneath these prevalence
      it's more efficient to immunize actively or passively without prior screening.

PMID- 7644885
TI  - [The acceptability of the health services contract by the primary care health
      professionals in Madrid: a qualitative research].
AB  - BACKGROUND: The objective of this paper is to study whether the Contrato Programa
      based management formula between INSALUD and Primary Care Managerships (CP) is
      known by INSALUD-Madrid primary care physicians and nurses, as well as which
      factors are influencing its acceptability. METHODS: Qualitative-based analysis
      and interpretation of the discussion had in five health personnel groups was
      used. RESULTS: The Health Service Contract is known by primary care health
      personnel as "self-management". This word induces them to think in the management
      of teams by their physicians themselves. Based on this self-management,
      physicians would plan staffs with minimal representation of nurses personnel, in
      exchange for increasing medical and administrative personnel, which in fact would
      solve their main problems, i.e. attendance pressure and bureaucracy, in addition
      to relationships with nurses. Determinants of this response relate to the
      satisfaction level with the Primary Care Reform attained by these collectives.
      This Reform has produced a "subjective equality" in both collectives, conditioned
      by fault in authority by physicians, which is desired by nurses and rejected by
      physicians. CONCLUSIONS: Health Service Contract in Primary Care is generally
      accepted by physicians, except for pediatricians, and rejected by nurses. Reasons
      are related to the ability from both collectives to recuperate the difference
      between them.

PMID- 7644886
TI  - [The evaluation of the preventive services for the pediatric population in
      Agaronese health centers].
AB  - BACKGROUND: We have shown the coverage of periodic health examinations made in
      children aged between 0 and 14 years old in Aragon during 1991, comparing with
      results obtained at national level and results obtained during 1990. METHODS: A
      descriptive transversal study was developed by reviewing clinic records of 9
      primary health centers selected by systematic sampling. Sampling consisted on 436
      histories. RESULTS: Main results were: age of child in the first visit: 83.5%
      below 1 month; metabolic disease screening: no data on 31.8%; DTP-polio: no data
      on 20.9%; triple viric: no data on 24.3%. CONCLUSIONS: Obtained data showed
      better results than those at national level. We should improve the metabolic
      diseases screening and vaccinations recording system.

PMID- 7644887
TI  - [Childhood accidents in primary health care].
AB  - BACKGROUND: Accidents in childhood are an important health problem, mainly in
      situations of social and environmental risk. Additionally, the lack of studies in
      primary health care, encouraged us to set up a study in order to establish the
      characteristics of accidents in childhood attended in a health center, their
      relation with the child's socio-familiar situation and medical care delivered.
      METHODS: We describe children's accidents occurred in our area (2,543 children 0
      14 years old, 788 of them living in deprived neighbourhoods) during 1992 attended
      in the health center. Study data was collected from data included in emergencies
      and medical records of the health center. We included information on: age, sex,
      socio-familiar situation, accident, lesion, and health care delivered
      characteristics. RESULTS: We include 623 accidents: annual cumulated incidence =
      245/1,000 children; males were more affected (58.4%); the accidents occurred
      mainly in the household (35.6%); the most frequent causes were blows (39.9%) and
      falls (30.5%); the most frequent lesions were injuries (29.7%) and blows (25.7%).
      Location of the lesions were the superior limbs (33.5%) and head and neck
      (25.98%). About 12.5% were delivered to the hospital, 17.8% of them required
      inpatient care, one died. Children of deprived boroughs have a relative risk of
      being attended for accident in our center of 4.2 (CI 95% = 3.64-4.84) compared
      with the rest of the area. 79 children have had repeated accidents, they occurred
      mainly in only 27 families, 92.6% of whom live in deprived areas. CONCLUSIONS:
      Our health center is attending a high frequency of children's accidents, most of
      them can be treated in the health center, the cases are concentrated in deprived
      boroughs and in risk families.

PMID- 7644888
TI  - [The adipose tissue of the orbit. Anatomic classification, therapeutic
      deductions].
AB  - There are two types of adipose tissue in the orbit. The yellow fat and the more
      abundant white, or orbital fat. Orbital fat cannot be dissociated from the
      contents of the orbit and plays an important role in ocular physiology and
      oculomotricity. Orbital fat is essential for aesthetic orbits. Graves' disease
      and anophthalmia. Adipose tissue in the orbit is particularly important in
      protecting the ocular globe from lateral wall trauma.

PMID- 7644889
TI  - [Fracture of the medial wall of the orbit. Apropos of 4 cases].
AB  - Fractures or the medial wall of the orbit are uncommon and clinical signs are
      often discreet. This report was focused on isolated fractures of the medial wall
      of the orbit. Blow-out trauma is usually the cause. In these cases the clinical
      signs ranged from simple ecchymosis to blindness by haematoma of the orbital
      cone. Computed tomography is a major tool for diagnosis and making therapeutic
      indications for these fractures. Treatment depends on the oculomotor involvements
      as measured by forced duction tests.

PMID- 7644890
TI  - [Histological classification of sarcomas].
AB  - Sarcomas are rare and malignant tumors of mesenchymatous origin. Numerous
      histological sub-types have been described. 10 to 15% of all sarcomas are located
      to head and neck. The more frequent histological types in this localization are
      fibrosarcoma, malignant fibrous histiocytoma and rhabdomyosarcoma. In this paper
      a general review of histological classification of sarcomas is proposed with a
      particular emphasis on head and neck sarcomas.

PMID- 7644891
TI  - [Sarcoma of the face occurring 13 years after irradiation of a retinoblastoma].
AB  - Morbidity of cancer treatments is well-known. Postradiation sarcomas have been
      reported though the relative risk is considered to be low. We report a case of
      osteogenic sarcoma of the face occurring 13 years after irradiation and
      chemotherapy of bilateral retinoblastoma. In this case chemotherapy, irradiation
      in the first years of life and retinoblastoma increased the risk of postradiation
      sarcoma.

PMID- 7644895
TI  - [Complete lateralization of the inferior alveolar nerve. A preliminary study,
      apropos of a case].
AB  - Inferior alveolar nerve lateralisation is a new technique. Mostly indicated in
      implantology, the techniques described are partial and located at the anterior
      part of the nerve, near the foramen mentalis. The authors describe a technique of
      total inferior alveolar nerve lateralisation, from the lingulae mandibulae to the
      foramen mentalis. Total lateralisation technique can be used in dental prosthesis
      (in mandibular posterior edentulism when the alveolar bone is reduced and when
      the prosthesis compresses the nerve in the foramen region), in implantology (when
      terminal implant restitution is needed), or in benign tumors (when the horizontal
      branch of the mandible is resected).

PMID- 7644892
TI  - [Orbital paraganglioma. Apropos of a case and review of the literature].
AB  - Paragangliomas are exceptional in the orbit. Among the 47 cases reported in the
      world literature more than 1/3 has been classified as alveolar soft part sarcoma.
      Diagnosis of paraganglioma was confirmed on the basis of pathology reports in
      only 10. We observed a case in a 46-year-old woman who presented with a tumour of
      the orbit. The histology examination and the ultrastructure determined by
      electron microscopy confirmed the diagnosis of paraganglioma. Characteristic
      histologic features are discussed together with a review of the literature.

PMID- 7644893
TI  - [Clinical, radiographic and axiographic control after traction-screw
      osteosynthesis of fractures of the mandibular condyle region].
AB  - Clinical, radiographic and electronic axiographic follow-up examinations were
      performed in 45 patients with a luxation or highly displaced fractures treated
      with traction screw fixation from 1984 to 1989. Axiographic findings gave an
      excellent objective evaluation of joint function. The excellent results achieved
      with traction screw fixation suggest that this method can be recommended for
      condyleal fractures of the mandible.

PMID- 7644894
TI  - [Limited mouth opening due to muscular fibrosis after locoregional anesthesia.
      Apropos of a case].
AB  - The amplitude of buccal opening was limited due to fibrosis of the middle
      pterygoideus muscle two months after a patient had undergone anaesthesia of the
      lower dental nerve trunk. Surgery was required. A physiological explanation was
      attempted based on other cases reported in the literature.

PMID- 7644896
TI  - Psychosocial work factors, physical work load and associated musculoskeletal
      symptoms among home care workers.
AB  - This study was based on a questionnaire and included a group of home care workers
      (HCW) (n = 305) and a reference group of municipal employees (n = 694). The
      relationship between the work environment and musculoskeletal symptoms was
      analysed. The HCW were less satisfied with their control over their work and
      stimulus from their work and had a higher physical work load and prevalence of
      musculoskeletal symptoms, compared with the reference group. The Rate Ratio (RR)
      of neck and shoulder symptoms among HCW was 83 and 54%, respectively, higher
      among those reporting a "high" psychological work load compared with those
      reporting a "low" load. The highest RR for a single risk indicator was 2.5, and
      this concerned low-back symptoms among HCW who often worked with twisted
      postures. A combination of "poor" psychosocial work environment and "high"
      physical work load produced the highest RR for work-related neck (RR = 2.57) and
      shoulder (RR = 2.13) symptoms.

PMID- 7644897
TI  - Facial EMG reactions to facial expressions: a case of facial emotional contagion?
AB  - The purpose of this study is to explore whether subjects exposed to stimuli of
      facial expressions respond with facial electromyographic (EMG) reactions
      consistent with the hypothesis that facial expressions are contagious. This study
      further examines whether males and females differ in facial EMG intensity. Two
      experiments demonstrated that subjects responded with facial EMG activity over
      the corrugator supercilii, the zygomatic major, the lateral frontalis, the
      depressor supercilii, and the levator labii muscle regions to stimuli of sad,
      angry, fearful, surprised, disgusted and happy faces, that, to large extent, were
      consistent with the hypothesis that facial expressions are contagious. Aspects of
      gender differences reported in earlier studies were found, indicating a tendency
      for females to respond with more pronounced facial EMG intensity.

PMID- 7644898
TI  - Psychophysiological arousal related to Type A components in adolescent boys.
AB  - The association between psychophysiological responses (heart rate, skin
      conductance and blood volume) and Type A behavior was studied in adolescent boys
      (n = 48) in computer-controlled experiments. Although psychophysiological arousal
      was related to the type of stress-evoking element, task-specificity did not
      result in significant psychophysiological differences between Type As and Nontype
      As. The indication is that physiological arousal may be a constitutional
      characteristic of Type A behavior. The multidimensionality of type A behavior
      must be considered in any investigation examining the psychophysiological Type A
      Nontype A differences. Different Type A dimensions, together with previously
      found psychological differences, were related to specific psychophysiological
      reactions.

PMID- 7644900
TI  - Adolescents' attitudes toward suicide, and a suicidal peer: a comparison between
      Swedish and Turkish high school students.
AB  - The present paper first presents the attitudes toward suicide and a suicidal
      classmate among 98 female and 69 male (N = 167) Swedish high school students.
      Secondly, the Swedish sample was compared with 167 (89 female and 78 male)
      Turkish high school students from a previous study. Among Swedish students, more
      males than females said that people have the right to commit suicide and suicide
      can be a solution to some problems. More females than males expressed a belief in
      life after death. Swedish adolescents were found to be holding more liberal
      attitudes toward suicide than Turkish adolescents. However, Turkish adolescents
      showed greater acceptance for a suicidal peer than Swedish adolescents. The
      results are discussed in terms of socio-cultural factors and related literature.
      The need for educational programs to provide basic knowledge about suicide and,
      effective ways of dealing with and helping suicidal peers is implicated.

PMID- 7644899
TI  - The role of emotionality and typicality in speechreading.
AB  - Two experiments were carried out to investigate how emotionality and typicality
      could influence speechreading performance. Typical and atypical sentences for a
      certain script, and emotional sentences (happy and sad content, presented with
      happy, sad or neutral facial expression) were shown without sound on a TV-screen.
      Two different scripts (restaurant and doctor) were used. In Experiment 1, hearing
      impaired subjects participated and in Experiment 2, normal-hearing subjects
      participated. Experiment 2 also evaluated the effects of tactile information. The
      results from both experiments showed that typical restaurant sentences were the
      easiest to speechread of all sentence-types, in line with script-theory (Abelson,
      1981; Anderson, 1983; Bellezza & Bower, 1981; Nottenburg & Shoben, 1980; Yekovich
      & Walker, 1986). For the doctor script, sad sentences were better speechread than
      happy sentences, also according to script-theory. In addition, perception of
      emotional content was enhanced by tactile information. Generally, both the
      cognitive and emotional effects are script-dependent, suggesting important social
      constraints on speechreading accuracy.

PMID- 7644901
TI  - Dissociative effects of elaboration on memory of enacted and non-enacted events:
      a case of a negative effect.
AB  - One experiment compared the effect of elaboration on enacted and non-enacted
      events. The commands were either presented in a basic form (e.g., "wave your
      hands") or in an enriched form. The commands were enriched by adding statements
      to the commands of how to perform the actions (e.g., "wave your hands as a
      conductor"). Free- and cued-recall data showed elaboration to have a dissociative
      effect on enacted and non-enacted events. Memory for the non-enacted events
      benefited from enrichment, whereas simple enacted events were remembered to a
      higher extent than complex enacted events. Lack of benefit from elaboration on
      memory of enacted events is suggested to be due to enactment leading to a
      sufficient degree of item-specific processing, and a negative effect of
      elaboration is suggested to occur when the way of manipulating item complexity
      decreases the familiarity of the actions. Familiarity ratings of the items by two
      independent groups of subjects supported this interpretation.

PMID- 7644903
TI  - Results of cardiovascular surgery in the Marfan syndrome. A retrospective study
      of 49 patients.
AB  - To evaluate the outcome of cardiovascular surgery in the Marfan syndrome, the
      records of 49 patients (median age 35 years) who underwent 60 operations were
      reviewed. Primary surgery was elective in 39 patients and emergency in ten. Non
      dissecting aneurysm with diameter 4-19 cm was present in 34 cases and distal,
      isolated aneurysm in four. In eight cases there was type A acute aortic
      dissection with median diameter 5.0 cm. One patient was operated on for mitral
      valve insufficiency, one for ventricular septal defect and one (acute) for
      endocarditis. Composite grafts were used for aortic root reconstruction.
      Operative complications occurred in 24% of the patients. The 30-day survival was
      92%. There were five (10%) late deaths. Survival after a median of 8 years
      postoperatively was 82%. The early and late results of cardiovascular surgery in
      the Marfan syndrome thus are concluded to be generally favourable. As late
      reoperation frequently is needed, however, close monitoring is advocated even
      after successful primary surgery.

PMID- 7644902
TI  - Improved long-term preservation of the coronary vasculature with University of
      Wisconsin solution.
AB  - Experiments were designed to investigate coronary vascular function after
      prolonged cold storage of isolated rat hearts, using University of Wisconsin (UW)
      solution. Hearts perfused with crystalloid cardioplegic solution (Plegisol) were
      used as controls. After perfusion with 10 ml at 4 degrees C, hearts were stored
      for 1 or 10 hours in the respective solutions at 4 degrees C. To evaluate
      coronary vascular function after perfusion and storage, endothelium-dependent
      vasodilation was induced with 5-hydroxytryptamine (5-HT) and smooth muscle
      dependent dilation with nitroglycerin (GTN). After perfusion only, or perfusion
      plus 1-hour storage, there was no intergroup difference in response to 5-HT and
      GTN. After 10-hour storage the vasodilatory response to 5-HT was abolished in the
      Plegisol group and slight vaso-constriction was observed, whereas in the UW group
      the vasodilatory effect of 5-HT persisted. The findings suggest that UW solution
      may be more favorable for prolonged cardiac preservation, as the coronary
      vascular reactivity was less affected.

PMID- 7644904
TI  - Intra- and postoperative cerebral complications of open-heart surgery.
AB  - A consecutive series of 1400 patients who had undergone open-heart surgery was
      retrospectively reviewed concerning postoperative cerebral dysfunction. The 30
      day mortality was 1.6%. Forty-one patients (2.9%) showed signs of cerebral
      dysfunction, which proved fatal in seven cases. Neurologic symptoms were observed
      immediately after surgery in 14 patients, suggesting intraoperative damage. In 20
      others there was an interval between surgery and the onset of cerebral symptoms,
      which in 12 cases were preceded by supraventricular tachycardia. Computed
      tomographic scans were performed on 27 patients and showed recent brain
      infarction in 22. No bleeding was found. At follow-up 34 of the 41 patients were
      alive, 21 of them with neurologic sequelae and 13 reporting complete recovery.
      Nineteen of the 34 survivors experienced no diminution of quality of life. Since
      half of the cerebral complications occurred postoperatively, more aggressive
      prevention and management of supraventricular tachyarrhythmia and anticoagulation
      therapy should be considered.

PMID- 7644905
TI  - Rhythm disturbances after blood and crystalloid cardioplegia in coronary artery
      bypass grafting.
AB  - One hundred consecutive patients scheduled for coronary artery bypass grafting
      were randomized to receive either blood or crystalloid cardioplegia. Successful
      Holter monitoring for rhythm disturbances was done before and immediately after
      the operation in 83 cases. With both modes of cardioplegia there were increases
      in the occurrence of rhythm disturbances postoperatively. The increases were
      mostly statistically significant. There was no intergroup differences in the
      occurrence of arrhythmias. The association between these disturbances and cross
      clamp times, myocardial temperatures during cross-clamping, myocardial
      fibrillation times during and after cross-clamping, CK-MB values and
      perioperative infarction all indicated ischaemia or incomplete myocardial
      protection as a major cause of the immediate postoperative rhythm disturbances.

PMID- 7644906
TI  - Doppler echocardiographic comparison of small (19 mm) bileaflet and pericardial
      heart valve prostheses in aortic position.
AB  - The resting haemodynamics of five types of small (19 mm) aortic valve prosthesis
      (2 bileaflet, 3 pericardial) were evaluated with Doppler echocardiography in 43
      patients. Two received St Jude Medical and six CarboMedics bileaflet valves and
      35 were given bioprostheses--16 Ionescu-Shiley, four Mitroflow and 15 Labcor
      Santiago. No significant differences in peak or mean transvalvular pressure drop
      or in effective valve area were found between the bileaflet and the pericardial
      valves or among the three types of bioprosthesis. All but one of the bileaflet
      prostheses showed a characteristic regurgitation pattern, with two lateral and
      one central jet, and 16 (46%) of the bioprostheses showed central regurgitation,
      but in no case were these jets haemodynamically significant. Thus the 19 mm
      bileaflet and the studied pericardial prostheses all have satisfactory resting
      haemodynamics, and all are suitable for implanting in small aortic roots.

PMID- 7644907
TI  - Late recurrence of thymoma and myasthenia gravis.
AB  - In a case of thymoma associated with myasthenia gravis, symptoms of relapse
      appeared 14 years after thymectomy. Tumour tissue from repeat resection showed
      the same histologic pattern and aneuploidy as in the original specimen. The case
      illustrates the necessity of wide surgical exposure to permit maximal thymectomy,
      though recurrence remains possible.

PMID- 7644908
TI  - Pulmonary arteriovenous fistula ruptured to pleural cavity in pregnancy.
AB  - Congenital pulmonary arteriovenous fistula is frequently associated with
      hereditary haemorrhagic telangiectasia (Rendu-Osler-Weber disease). With the
      increased blood flow in pregnancy such fistulas enlarge, occasionally giving rise
      to haemothorax, which generally has a poor prognosis. A familial case is
      presented in which massive haemothorax required emergency thoracotomy in the 27th
      week of pregnancy.

PMID- 7644909
TI  - Gastroepiploic artery as an in situ coronary artery bypass graft: evaluation of
      MRI and colour Doppler ultrasound in follow-up.
AB  - The right gastroepiploic artery, increasingly used as an in situ coronary artery
      bypass graft, has good long-term patency. This study aimed to assess the accuracy
      and limitations of magnetic resonance imaging (MRI) and colour Doppler ultrasound
      (US) in postoperative follow-up of such cases. In eight consecutive patients (6
      men, 2 women, mean age 57 years), conventional angiography, MRI and US were
      performed to evaluate graft patency. Colour Doppler US, performed within a week
      of the operation, correctly detected flow in three patent grafts. MRI (1.5 tesla)
      was performed c. 17 months after surgery, using a spine coil and a coronal two
      dimensional Flash-type imaging sequence. At angiography six of the eight
      gastroepiploic artery grafts were patent, and two were occluded. The sensitivity
      and specificity of MRI were 100%. This accuracy makes MRI a promising method for
      noninvasive post-operative evaluation of right gastroepiploic artery graft
      patency.

PMID- 7644910
TI  - Human campylobacter infections: epidemiology and control.

PMID- 7644911
TI  - Determination of aluminium in liver from reindeer, moose and sheep by
      electrothermal atomic absorption spectrometry.
AB  - Aluminium in liver from reindeer, moose and sheep from the northeast part of
      Norway was determined by graphite furnace atomic absorption spectrometry
      following digestion of the samples with nitric acid. The concentration of
      aluminium in the liver was markedly higher for reindeer than for moose and sheep;
      the median values obtained were 0.56 microgram g-1 Al (wet wt.) for 101 reindeer,
      0.06 microgram g-1 Al for 72 moose and 0.09 microgram g-1 Al for 40 sheep. The
      detection limit of the method was 0.01 microgram g-1 Al. The NIST SRM 1577a
      Bovine Liver was also analyzed.

PMID- 7644912
TI  - An estimation of the uptake of mercury from amalgam fillings based on urinary
      excretion of mercury in Swedish subjects.
AB  - Mercury is released from amalgam fillings in several forms, i.e. as elemental
      vapour, ions and in fine particles. Despite many investigations there is still
      considerable uncertainty concerning the uptake of such mercury. Most available
      estimates have calculated the pulmonary uptake of mercury vapour based on
      measurements of concentrations intra-orally or in expired breath. Presented
      estimates vary by an order of magnitude from approximately 1 to 20
      micrograms/day. The possibility of estimating this uptake based on levels of
      mercury in a biological index medium has received comparatively little attention.
      The purpose of the present work is to estimate the uptake of mercury from amalgam
      fillings based on urinary concentrations of mercury. It is estimated that the
      average uptake of mercury from amalgam fillings in Swedish subjects is within the
      interval 4-19 micrograms/day. This interval was arrived at after a detailed
      evaluation of the uncertainties in the data used and in the different
      assumptions. Notwithstanding the considerable range of this estimate it indicates
      a higher uptake than several other estimates, some of which have had a large
      impact on the scientific debate concerning this issue.

PMID- 7644914
TI  - Sister Arthur on health volunteers overseas project.

PMID- 7644913
TI  - Focus on South Dakota Health 2000: putting prevention into practice. Protecting
      our employees: the role of the professional nurse. Part 1.

PMID- 7644915
TI  - [Role of the subacromial space on development of the impingement syndrome. I].
AB  - In the first part of the study reported in this paper the anatomy of 150 scapulae
      was studied to find out whether variation in the subacromial space might cause
      impingement syndrome. Sixteen different parameters, including various angles,
      size and shape of the acromion and the coracoid process, and length of the
      coracoacromial ligament and the acromion, were measured. Soft tissue was
      completely removed from the bone, so that no statement on the rotator cuff was
      possible. The data were processed using the Tukey LSD test. A statistically
      significant correlation between the size of the shoulder blade and the length of
      the acromion and the coracoacromial ligament was found. The shape of the coracoid
      process showed more individual variations, and no correlation with the size of
      the bony scapula was found. The shape of the subacromial space was obtained by
      using four different bony landmarks (acromial angle, tip of the anterior rim of
      the acromion, tip of the coracoid process and supraglenoid tubercle). Three
      different types were found: a "rhomboid" in 103 cases, an approximate "kite"
      shape in 35 cases, and a triangle in 12 cases. The rhomboid form means a larger
      plane surface, so that the rotator cuff can glide more smoothly than with the
      other types. The different shapes of the subacromial space did not influence the
      slope of the acromion in the scapular plane.

PMID- 7644916
TI  - [Role of the subacromial space on development of the impingement syndrome. II].
AB  - Twenty-five patients with suspected impingement syndrome on the basis of clinical
      examination were evaluated by magnetic resonance imaging (MRI). In paracoronal
      and parasagittal planes, different measurements of bony structures of the
      subacromial space and of the glenoid joint were performed, as in the anatomical
      study reported in the companion paper. A healthy, age-and sex-matched group of 25
      persons underwent the same MRI-procedure and the results were compared with those
      in the patients. Ruptures of the rotator cuff were excluded by means of standard
      X-rays, physical examination, and ultrasound. The comparison revealed a highly
      significant difference between the sizes of the subacromial space. Healthy
      persons had a space that was larger by more than one third than that of the
      patients. Other parameters did not differ significantly between the two groups.
      In a further part of the study the insertion zone of the coracoacromial ligament
      into the undersurface of the acromion was histologically studied in 24 autopsy
      specimens. Different staining techniques were used to find out whether
      microscopic changes occur during different stages of life. Cartilage without bone
      formation of the acromion was found in children. In adult specimens bony
      projections of the undersurface of the acromion and thickening of the surrounding
      fibrocartilage were found, but there was no correlation between ageing and these
      changes. However, in patients suffering from impingement syndrome the subacromial
      space is reduced. Acromioplasty enlarges the space by resection of the anterior
      part of the acromion. Bony spurs on the acromion and a thickening of the
      fibrocartilaginous layer are not degenerative changes, but they are caused by
      increased tensile strength of the coracoacromial ligament and are not influenced
      by age.

PMID- 7644917
TI  - [Classification and osteosynthesis technique of calcaneus fractures. External
      fixator as temporary distractor].
AB  - In the treatment of fractures of the calcaneus, the particularly intricate local
      anatomy, complicated fracture forms and associated soft tissue damage often
      prejudice operative, anatomical reconstruction. We propose a simplified
      classification that is based on the Regazzoni classification of 1993 and has six
      grades of severity. It can be helpful in the selection of operative treatment
      and, above all, make it possible to recognize whether operative reconstruction is
      possible and appropriate. When operative reconstruction is indicated we find the
      secondary operation important; it is also important to diagnose and treat
      compartment syndrome if present and otherwise to take steps to prevent it. In the
      first phase, in special cases we use an external fixator without reconstruction
      of the full length. The operative technique is largely standardized as as the
      fixator is placed only temporarily. Correct positioning allows easy correction of
      shortening or varus deformation, and joint surface reconstruction is also
      feasible. Autologous bone grafting is possible. The definitive fixation is
      achieved with internal plate stabilization by a lateral approach and removal of
      the fixator. Contraindications for this procedure are burst fractures with total
      destruction of the joint surfaces and cartilage. Out of 54 fractures we used the
      fixator to aid reduction in 45. In 71% of these we had very good and good results
      according to the Merle d'Aubigne scoring system.

PMID- 7644918
TI  - [Concomitant injuries with anterior cruciate ligament rupture. A retrospective
      study].
AB  - We identified 107 consecutive patients with anterior cruciate ligament (ACL)
      rupture who underwent arthroscopy after trauma. The results of the preoperative
      clinical examination and the arthroscopic findings of associated injuries to the
      knee are shown. Some 55% of the acute ACL ruptures involved a tear of the lateral
      meniscus, 45% of the medial meniscus, and 34% had a lesion of the medial
      collateral ligament. The most frequent combination of injuries with ACL rupture
      was a tear in both menisci and a lesion of the medial collateral ligament with a
      tear in the lateral meniscus. The preoperative examination revealed the ACL
      rupture in 94% of uses but the lateral meniscal lesion in only 32%. At the time
      of operation 29% of all associated injuries had not been discovered. These
      results show that--independent of the time of reconstruction of the thorn ACL-
      acute rupture of the ACL is an indication for arthroscopy.

PMID- 7644919
TI  - [Clinical and roentgenologic 5 year follow-up of modified Evans-plasty in chronic
      lateral instability of the ankle joint].
AB  - Between 1984 and 1989, 108 patients who had chronic lateral instability of the
      ankle were treated with a modified Evans tenodesis, in which the anterior half of
      the peroneus brevis tendon was used for reconstruction. Follow up was possible by
      questionnaire in 75 patients and by clinical examination in 46, after 29-122
      months (mean 68 months). Subjectively excellent or good results were achieved in
      62 patients (82.6%) while 9 (12%) had fair results and 4 (5.4%) a poor outcome.
      Pain during physical activity was reported by 27 patients (35%), loss of
      inversion by 34 (45%) and slight instability by 31 (41%). The X-ray films at
      follow-up revealed more signs of arthrosis than had been present preoperatively.
      The stress tests showed an anterior drawer of 7.8 mm preoperatively and 7.0 mm
      postoperatively (p = 0.03); talar tilt was improved from 7.7 degrees to 4.5
      degrees (p < or = 0.01). The outcome reported by the patients and the objective
      results of the clinical and radiological examinations were at odds. Pain,
      instability and osteophyte formation after the operation were so frequent because
      the talus was not fixed when the Evans reconstruction was implemented. Therefore,
      we suggest that this method should not be used in patients with a high activity
      level.

PMID- 7644920
TI  - [Results of long-term therapy of chronic, post-traumatic osteomyelitis with
      gentamycin PMMA chains].
AB  - From 1977 to 1983, 173 patients suffering from chronic posttraumatic
      osteomyelitis were treated by local debridement and implantation of septopal
      beads; 102 patients were subsequently evaluated after follow-up periods of
      between 4 and 10 years. In 89.2% of these cases cure was achieved during the
      initial hospital stay. In 15.7% further debridements were necessary during the
      initial hospital stay to manage infection. In 91 patients there was no early
      recurrence until 1983. After 1983 only 7 patients had late recurrences. At the
      time of follow up 95 patients (94.5%) did not show any signs of infection. It was
      necessary for 9 patients to change their profession because of the disease. Full
      use of the extremity involved was reported by 45 patients, and some slight
      limitations by 46. In 11 cases the patients could not use the extremity involved
      in activities of daily living. In mono-infections (87.2%) and in infection with
      multiple different pathogen chains (82%) Staphylococcus aureus was by far the
      most common pathogen. Our findings indicate that both the outcome and the
      prognosis score are significantly better after the treatment regimen used than
      after other treatment modalities.

PMID- 7644921
TI  - [Ilisarov callus distraction and callus compression in treatment of defect
      gunshot fractures, pseudarthroses and post-traumatic deformities in developing
      countries. A report of experiences in Cambodian and Ethiopian provincial
      hospitals].
AB  - Between March 1989 and May 1993, a total of 22 patients were treated by
      Ilisarov's method of callus distraction and compression in provincial hospitals
      in Cambodia and Ethiopia. In both countries were times of civil war and unrest.
      The indications were high-velocity gunshot and explosive injuries with defect
      fractures (9 patients), infected and non-infected non-unions after gunshot
      injuries (6 patients) and civil accidents (3 patients), and deformities after
      civil accidents and gunshot injuries (4 patients). The deformities were leg
      shortening by between 5 and 7 cm and in 1 case ankylosis of the knee joint in 110
      degrees flexion. A simple unilateral or V-shaped external fixator with devices
      for distraction and compression was applied. The results in 19 patients are
      known, while 3 patients have been lost to follow-up since discharge. In 1 case of
      an infected defect fracture (12 cm) fo the femur amputation was necessary because
      of sepsis. In all 6 other cases the bone defects were bridged by means of
      segmental transport, distraction and compression; in all 3 cases of shortening it
      was possible to restore the original length; similarly, in the case of knee joint
      ankylosis flexion of 10 degrees was achieved. All 5 infected non-unions healed
      well after sequesterectomy and segmental bone transport with distraction and
      compression, and the same holds for the 3 non-infected non-unions. However, in 7
      cases a minor spongiosa bone graft was needed to consolidate the ossification at
      the contact point after distraction and/or compression.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7644922
TI  - [Outcome of total arthrodesis of the hand].
AB  - In cases of degeneration combined with pain and instability of a wrist joint,
      fusion of the joint is clearly indicated. A retrospective review of 39 patients a
      mean of 7 years after operation suggested that radiocarpal arthrodesis had been
      successful. Fusion of the 39 wrist joints was accomplished by means of an AO
      plate and cancellous bone grafting. Most patients achieved good function and were
      completely free of symptoms even during heavy work. Especially for patients with
      rheumatoid wrist joints and those engaged in hard manual labour subtotal
      arthrodesis cannot be recommended since the functional results are only
      negligibly better than those obtained with total arthrodesis.

PMID- 7644923
TI  - Phase I studies of continuous-infusion paclitaxel given with standard aggressive
      radiation therapy for locally advanced solid tumors.
AB  - Currently available therapies are unsatisfactory for locally advanced solid
      tumors of the lung, head and neck, and brain. Laboratory data suggest that the
      addition of paclitaxel (Taxol; Bristol-Myers Squibb Oncology, Princeton, NJ), a
      microtubule-stabilizing drug, to radiation therapy may result in significant
      radiation sensitization, perhaps because paclitaxel induces cell cycle arrest at
      G2/M. Relatively low concentrations, 1 to 10 nmol/L, appear to be optimal for
      direct cytotoxicity and radiosensitization in vitro. Within this dose range, more
      prolonged exposure seems to result in higher response rates. We are conducting
      phase I trials designed to test continuous infusion (24 hours per day, 7 days per
      week) intravenous paclitaxel combined with standard curative-intent radiation
      therapy. To date, 22 patients are evaluable, and the maximum tolerated dose of
      paclitaxel has not been reached at up to 2.5 mg/m2/d. Observed toxicities include
      anemia, lymphopenia, mucositis, and cutaneous erythema/desquamation.

PMID- 7644924
TI  - A phase I study of carboplatin and paclitaxel in non-small cell lung cancer: a
      University of Colorado Cancer Center study.
AB  - This phase I study was designed to determine the maximal tolerated doses of
      carboplatin and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ),
      as well as the safety and efficacy of these agents, in patients with advanced,
      nonresectable stages IIIB and IV non-small cell lung cancer. Paclitaxel was given
      as a 3-hour intravenous infusion followed by a 30-minute infusion of carboplatin.
      Patients were assigned to one of seven treatment groups in which paclitaxel and
      carboplatin were given in doses ranging from 135 to 225 mg/m2 and from 250 to 400
      mg/m2, respectively. Overall, the two-drug combination has been well tolerated.
      The major dose-limiting toxicity has not been reached but will likely be
      neutropenia. There appears to be a dose-response relationship: two partial
      responses (12%) were observed among 17 patients assigned to the lower-dose
      groups, whereas six (50%) of 12 evaluable patients in the higher-dose groups
      achieved partial responses. The maximal tolerated doses have not been reached
      yet, and will be at least 200 mg/m2 for paclitaxel and 400 mg/m2 for carboplatin.

PMID- 7644925
TI  - Paclitaxel plus carboplatin for advanced lung cancer: preliminary results of a
      Vanderbilt University phase II trial--LUN-46.
AB  - Based on their good activity and minimal toxicity in non-small cell lung cancer
      and other cancers, we initiated a phase II trial of carboplatin plus paclitaxel
      (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in the treatment of patients
      with previously untreated stage IIIB and IV non-small cell lung cancer. Among 51
      patients treated, the overall response rate was 27.5% (14 partial responses).
      Seventeen patients had stable disease, while 16 patients experienced disease
      progression after two cycles of treatment. Apart from myelosuppression, toxicity
      has been modest, with fewer than 5% of patients experiencing grade 3 or greater
      nonhematologic toxicity. Objective response and survival rates were modestly
      improved among patients given the higher of two paclitaxel doses (175 mg/m2 v 135
      mg/m2). These data suggest that paclitaxel plus carboplatin warrants further
      study in metastatic non-small cell lung cancer.

PMID- 7644926
TI  - Concurrent paclitaxel/cisplatin with thoracic radiation in patients with stage
      IIIA/B non-small cell carcinoma of the lung.
AB  - Nine patients with stage IIIB non-small cell lung cancer were entered into a
      phase II trial designed to determine the feasibility of giving a combination of
      paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) plus cisplatin
      concurrent with thoracic radiation. Paclitaxel was given as a 24-hour infusion
      (135 mg/m2) followed by cisplatin (75 mg/m2) every 4 weeks, for a total of four
      cycles. Thoracic radiation was given concurrently with the first two cycles of
      chemotherapy, for a total dose of 64.8 Gy over 6 weeks. Neutropenia and
      esophagitis were the most common toxicities, with 66% of patients experiencing
      grade 3 or 4 neutropenia and 55% experiencing grade 3 or 4 esophagitis. Grade 3
      pulmonary toxicity developed in 33% of patients. All patients were able to
      receive the full dose of radiation, although half of the patients required some
      modification of the chemotherapy regimen. There was one complete response and
      four partial responses, yielding a 56% overall response rate. This study
      demonstrates that it is feasible to treat patients with stage IIIB non-small cell
      lung cancer with paclitaxel/cisplatin plus concurrent thoracic radiation, with a
      degree of toxicity comparable with that associated with a degree of toxicity
      comparable with that associated with other concurrent combined-modality regimens
      for this disease.

PMID- 7644927
TI  - Carboplatin/etoposide/radiation plus escalating doses of paclitaxel in stage III
      non-small cell lung cancer: a preliminary report.
AB  - Large randomized studies have shown superior survival results for sequential
      chemoradiotherapy compared with radiation alone in stage III non-small cell lung
      cancer. Similarly, chemotherapy followed by surgery was associated with longer
      survival than surgery alone in small randomized trials. Despite these results,
      disease recurs in most stage III patients. To improve these results, we are
      studying escalating doses of paclitaxel (Taxol; Bristol-Myers Squibb Company,
      Princeton, NJ) combined with platinum/etoposide and simultaneous thoracic
      irradiation as preoperative and curative therapy. Initially, paclitaxel was given
      at a starting dose of 35 mg/m2 intravenously (i.v.) over 24 hours on days 1 and
      8; carboplatin (area under the concentration time curve) 4 mg/mL.min) i.v. was
      given on day 2 and etoposide 5 mg/d orally on days 1 to 5 and 8 to 12; cisplatin
      50 mg/m2 i.v. was given on day 23, and radiation 2 Gy was given on days 1 to 5
      and 8 to 12. Courses were repeated every 28 days. Four of five patients treated
      at the second paclitaxel dose level (90 mg/m2) experienced grade 4 toxicity. The
      treatment regimen was changed to paclitaxel given at a starting dose of 80 mg/m2
      i.v. over 3 hours on day 1, carboplatin (area under the concentration time curve
      4 mg/mL.min) i.v. given immediately after paclitaxel, etoposide 40 mg/m2 i.v.
      given over 1 hour on days 2 to 5, and radiation 2 Gy given on days 1 to 5 and 8
      to 12. No grade 4 toxicity was observed in five patients treated at the first
      paclitaxel dose level (80 mg/m2). After two courses, pulmonary resection
      (lobectomy and pneumonectomy) was performed without fatalities in five patients.
      Although more data are needed, pulmonary resection appears feasible following
      treatment with this paclitaxel-containing regimen. Patient accrual is continuing
      to determine the maximum tolerated dose of paclitaxel.

PMID- 7644928
TI  - Phase I study of paclitaxel as a 3-hour infusion followed by carboplatin in
      untreated patients with stage IV non-small cell lung cancer.
AB  - Preliminary results of a phase I study of paclitaxel (Taxol; Bristol-Myers Squibb
      Company, Princeton, NJ), given by 3-hour infusion, followed by carboplatin in
      chemotherapy-naive patients with stage IV non-small cell lung cancer indicate
      that both agents can be combined at clinically relevant single-agent doses. The
      paclitaxel (mg/m2)/carboplatin area under the concentration-time curve
      (mg.min/mL) dose level of 225/7 is projected to be the maximally tolerated and
      recommended phase II dose level for future evaluations. Dose-limiting
      neutropenia, thrombocytopenia, and nausea and vomiting preclude treatment with
      carboplatin doses estimated to target an area under the concentration-time curve
      of 9 mg.min/mL when given with paclitaxel 225 mg/m2. The heterogeneous nature of
      the principal toxicities, as well as the ability to administer clinically
      relevant single-agent doses of both agents in combination, also indicate that
      further dose escalation of paclitaxel and carboplatin using hematopoietic growth
      factors would not be feasible. The preliminary antitumor activity noted to data,
      as well as the safety associated with the clinically relevant single-agent doses
      that can be given in combination, indicate that phase II/III evaluations of this
      regimen are warranted in patients with both advanced and early stage non-small
      cell lung cancer.

PMID- 7644929
TI  - Preliminary analysis of a phase II study of weekly paclitaxel and concurrent
      radiation therapy for locally advanced non-small cell lung cancer.
AB  - Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) is an attractive
      agent to combine with radiation for non-small cell lung cancer. We have been
      conducting clinical trials of weekly paclitaxel and concurrent radiation therapy.
      In a phase I study in non-small cell lung cancer, we determined the maximum
      tolerated dose of paclitaxel to be 60 mg/m2/wk with radiation. Patients received
      paclitaxel 60 mg/m2/wk as a 3-hour infusion for 6 weeks with radiation to the
      primary tumor and regional lymph nodes (40 Gy) followed by a boost to the tumor
      (20 Gy). From March 1994 to February 1995, 33 patients have been entered by the
      Clinical Oncology Group of Rhode Island. The overall response rate (complete plus
      partial responses) of 25 evaluable patients as of March 1995 was 84%, with a
      confidence interval of 68 to 96. The major toxicity was esophagitis. Twenty
      percent of patients had grade 4 esophagitis. Only 8% of patients had grade 3
      neutropenia. Combined-modality therapy with paclitaxel and radiation is a
      promising treatment for locally advanced non-small cell lung cancer with a high
      response rate and acceptable toxicity.

PMID- 7644930
TI  - Management (chemotherapy/best supportive care) of advanced-stage non-small cell
      lung cancer.
AB  - Non-small cell lung cancer (NSCLC) represents almost three quarters of all cases
      of lung cancer. Most NSCLC patients present with either locally advanced
      inoperable disease, stage IV metastatic disease, or comorbid medical conditions
      that make them unsuitable for curative resection. Among NSCLC patients in the
      United States, overall 5-year survival rates range from 10% to 15%. Systemic
      chemotherapy has had minimal impact on prolonging survival or improving quality
      of life. Combination chemotherapy regimens containing cisplatin usually produce
      the best overall response rates. Combination chemotherapy in one study also has
      been shown to be more efficacious and less expensive than best supportive care.
      Newer cytotoxic agents, including vinorelbine, gemcitabine, paclitaxel (Taxol;
      Bristol-Myers Squibb Company, Princeton, NJ), docetaxel, and the camptothecins,
      have shown promise in the treatment of NSCLC. In combination with other effective
      agents (eg, cisplatin), response rates approaching 50% have been observed. A
      greater understanding of the biologic properties of lung cancer may help
      facilitate early detection and chemoprevention in patients at risk.

PMID- 7644931
TI  - Paclitaxel 3-hour infusion given alone and combined with carboplatin: preliminary
      results of dose-escalation trials.
AB  - Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) by 3-hour
      infusion was combined with carboplatin in a phase I/II study directed to patients
      with non-small cell lung cancer. Carboplatin was given at a fixed target area
      under the concentration-time curve of 6.0 by the Calvert formula, whereas
      paclitaxel was escalated in patient cohorts from 150 mg/m2 (dose level I) to 175,
      200, 225, and 250 mg/m2. The 225 mg/m2 level was expanded for the phase II study
      since the highest level achieved (250 mg/m2) required modification because of
      nonhematologic toxicities (arthralgia and sensory neuropathy). Therapeutic
      effects were noted at all dose levels, with objective responses in 17 (two
      complete and 15 partial regressions) of 41 previously untreated patients.
      Toxicities were compared with a cohort of patients in a phase I trial of
      paclitaxel alone at identical dose levels. Carboplatin did not appear to add to
      the hematologic toxicities observed, and the paclitaxel/carboplatin combination
      could be dosed every 3 weeks.

PMID- 7644932
TI  - Paclitaxel by 1-hour infusion in combination chemotherapy of stage III non-small
      cell lung cancer.
AB  - We report our preliminary phase II experience with paclitaxel (Taxol; Bristol
      Myers Squibb Company, Princeton, NJ) given as a I-hour infusion with cisplatin,
      etoposide, and concurrent radiotherapy to patients with unresectable stage IIIA
      or IIIB non-small cell lung cancer. Twenty-three patients have been started on
      therapy, with 15 thus far completing treatment. Eight of 15 patients have
      achieved complete or "near complete" responses, and five more patients have had
      partial responses. No patients experienced disease progression. The combined
      modality regimen was well tolerated, with the exception of grade 3 or 4
      esophagitis, which usually occurred during the last 2 weeks of radiation therapy
      (eight patients). It is hoped the results of these and other studies will help
      clarify the role of paclitaxel in multimodality therapy for lung cancer.

PMID- 7644933
TI  - Traumatic hip dislocation: early MRI findings.
AB  - PURPOSE: Objective of this study was to present the spectrum of early magnetic
      resonance imaging (MRI) findings following traumatic dislocation of the femoral
      head, and to identify any associated injuries that may have therapeutic or
      prognostic significance and be better delineated by MRI than by conventional
      radiography. PATIENTS AND METHODS: Prospective MRI of both hips was formed on 18
      patients (14 male, 4 female; age range 14-54 years; average age 30.5 years)
      within 5 weeks of a traumatic femoral head dislocation. The interval between the
      time of injury and the time of injury and the imaging studies ranged from 2 to 35
      days (average 13.2 days). Posterior dislocation was present in 14 patients and
      anterior dislocation in 4 patients. In the majority of cases, we performed axial
      T1, coronal T1, and coronal T2* (MPGR) sequences. Images were retrospectively
      evaluated by consensus of three radiologists for possible abnormalities of the
      bone and cartilage, joint space, and soft tissues. Because all patients were
      treated with closed reduction, surgical correlation was not obtained. RESULTS:
      All patients had a joint effusion or hemarthrosis. Of the 14 patients with
      posterior dislocation, isolated femoral head contusions (trabecular
      microfractures) were identified in 6 patients. Four patients had small femoral
      head fractures, and one had an osteochondral defect. Acetabular lip fractures
      were seen in six patients, and one patient had a labral tear. Four patients had
      intra-articular loose bodies and one had ligamentum teres entrapment. Twelve
      patients had iliofemoral ligament injury. All patients had muscle injury
      involving the gluteal region and medical fascial compartment, and 13 patients had
      anterior fascial compartment muscle injury. Seven patients with posterior
      dislocation had posterior fascial compartment injury. Of the four patients with
      anterior dislocation, two had bony contusion, two had cortical infraction, one
      had a labral tear, and all four had an iliofemoral ligament injury. All four
      patients in this group had muscle injury of the gluteal region and of the
      anterior and medial fascial compartments. CONCLUSIONS: MRI can effectively
      identify and quantify the muscle injury and joint effusion that invariably
      accompany traumatic hip dislocations. It is also useful for demonstrating
      trabecular bone contusion (trabecular injury) and iliofemoral ligament injury,
      which occur commonly with acute hip dislocation.

PMID- 7644934
TI  - Partial ACL rupture: an MR diagnosis?
AB  - PURPOSE: We sought to clarify the ability of magnetic resonance imaging (MR) to
      show partial anterior cruciate ligament (ACL) ruptures and to allow distinction
      of partial from complete ACL ruptures. MATERIALS AND METHODS: Eighty-eight
      patients were studied by arthroscopy and MR (36 with normal ACLs, 21 with partial
      ACL ruptures, and 31 with complete ACL ruptures). MR studies were interpreted by
      an experienced, blinded reader. MR examinations were also independently scored
      with respect to four primary and seven secondary signs, and these data were
      analyzed using discriminant analysis. RESULTS: The sensitivity of MR is lower for
      partial than for complete ACL ruptures. Most detected partial ACL ruptures
      resemble complete ruptures on MR. Secondary signs do not significantly improve
      detection of partial ACL ruptures, but they do help to distinguish partial from
      complete ACL ruptures. Displacement of the posterior horn of the lateral meniscus
      and popliteus muscle injury are indicative of complete ACL rupture. CONCLUSIONS:
      The majority of partial ACL ruptures are shown by MR, but MR is less sensitive
      for partial than for complete ACL rupture. The distinction of partial from
      complete ACL rupture on MR examination, while problematic, is slightly improved
      by assessment of secondary signs.

PMID- 7644935
TI  - Intramuscular ganglia arising from the superior tibiofibular joint: CT and MR
      evaluation.
AB  - OBJECTIVE: To evaluate the role of magnetic resonance imaging (MRI) and computed
      tomography (CT) in the diagnosis of intramuscular ganglia (IMG) that arise from
      the superior tibiofibular joint (STFJ). MATERIAL AND METHODS: Our series
      consisted of three men and three women. Four patients were studied by MRI, one by
      CT only, and two by both modalities. Contrast was used in one of the two patients
      studied by CT. MRI was obtained in at least two orthogonal planes to demonstrate
      the relation of the ganglia to STFJ. RESULTS: The MR and CT appearance of these
      ganglia was basically that of a well-defined soft tissue mass with low
      attenuation on CT images consistent with the presence of fluid. On MR studies,
      they had an isointense signal on T1-weighted images and a homogenous high
      intensity signal on T2-weighted images. MRI demonstrated the attachment of these
      ganglia to the STFJ. CONCLUSION: CT and MRI were effective, noninvasive
      modalities in the evaluation of IMG. The imaging features on both modalities were
      consistent with the presence of fluid- containing lesions that had close
      proximity and were attached to the STFJ. The combination of location and the
      fluid consistency of these lesions facilitated the diagnosis.

PMID- 7644936
TI  - Synovial haemangioma of the knee: a frequently misdiagnosed lesion.
AB  - OBJECTIVE: The objective of this study was to assess the contribution of magnetic
      resonance (MR) imaging in the diagnosis and surgical planning of five cases of
      synovial haemangioma of the knee. PATIENTS AND METHODS: The clinical,
      radiological and arthroscopic features of five pathologically proven synovial
      haemangiomas of the knee were retrospectively reviewed. RESULTS: A diagnostic
      delay, on average of 8 years, had occurred in four of the cases. Plain films were
      unremarkable, except for one case with arthropathy mimicking haemophilia,
      Arteriography, performed in three patients, was normal in one. CT, performed in
      three patients, showed the lesion, but the extent of the latter was better
      demonstrated with MR imaging. Synovial haemangiomas had a high signal intensity
      of T2-weighted images, without any extensive mass effect. Fibrofatty septa within
      the lesion were observed in three cases and muscular and/or fatty invasion in
      two. Arthroscopy allowed diagnosis of the lesion in two cases, but showed only
      nonspecific synovitis in another two. CONCLUSION: This study emphasizes the
      valuable contribution of MR imaging in the diagnosis and surgical planning of
      synovial haemangiomas.

PMID- 7644937
TI  - Pedicular: of lice and men.

PMID- 7644938
TI  - Hyperextension strain or "whiplash" injuries to the cervical spine.
AB  - PURPOSE: To define "whiplash" radiologically. MATERIAL AND METHODS: A full
      cervical spine radiographic series (including flexion and extension views) was
      reviewed in 40 patients with clinically proven "whiplash" injuries and compared
      to the radiographs in 105 normal controls. The level and degree of kinking or
      kyphosis, subluxation, and the difference in the amount of fanning between
      spinous processes on flexion and extension films were measured in each patient.
      RESULTS: Localized kinking greater than 10 degrees and over 12 mm of fanning,
      often occurring at the level below the kinking or kyphosis, occurred mainly in
      the group of whiplash patients (sensitivity 81%, specificity 76%, accuracy 80%).
      CONCLUSIONS: Localized kinking greater than 10 degrees and fanning greater than
      12 mm are useful measurements by which to separate patients with true whiplash
      injuries from those with minor ligamentous tears. Flexion and extension views are
      essential to help define whiplash and other ligamentous injuries of the cervical
      spine.

PMID- 7644939
TI  - The role of MR imaging in the diagnosis of alveolar soft part sarcoma: a report
      of 10 cases.
AB  - OBJECTIVE: The objective of this study was to analyze the characteristics of
      alveolar soft part sarcoma using magnetic resonance imaging (MRI). DESIGN: MRI
      studies of pathologically proven alveolar soft part sarcomas (ASPS) in ten
      patients were reviewed and compared with computed tomographic (CT) studies and
      angiograms. PATIENTS: Ten patients presented with a soft tissue mass of the
      extremities, neck, axilla, or buttocks. MR images were obtained in all patients
      prior to surgical intervention, chemotherapy, or irradiation. RESULTS AND
      CONCLUSION: Although most soft tissue sarcomas are isointense relative to muscle
      or MRI T1-weighted images (T1WI), nine of the ten alveolar ASPS in the present
      study demonstrated high signal intensity on both T2 and T1WI. Flow voids were
      observed both at the core and at the margins of the tumors studied. Recognition
      of these characteristic MRI findings may lead to the early diagnosis of ASPS,
      especially when the clinical presentation is that of a slow-growing soft tissue
      mass in a young adult patient.

PMID- 7644940
TI  - Longitudinal computed tomography of the scaphoid: a new technique.
AB  - Computed tomography is increasingly utilized for the evaluation of scaphoid
      fracture, nonunion, and deformity. We have developed a new technique of
      positioning patients while performing longitudinal computed tomography of the
      scaphoid. With the wrist positioned in radial deviation and neutral flexion,
      greater patient comfort is provided and immobilization of the wrist is not
      required. A reproducible image can be obtained with attention to the alignment of
      the scanning plane to the longitudinal axis of the scaphoid on the scout image,
      and verified with the "target sign". High resolution images, which clearly
      demonstrate the abnormalities of the scaphoid, can be produced even if the
      patient has a cast on the wrist or if there is hardware in situ.

PMID- 7644941
TI  - Spiral CT with multiplanar reconstruction in the diagnosis of sternoclavicular
      osteomyelitis.
AB  - OBJECTIVE: The purpose of this study was to determine whether contrast-enhanced
      spiral ct scanning supplemented by multiplanar reconstruction is of value in the
      evaluation of suspected infection of the sternoclavicular joints. MATERIALS AND
      METHODS: Seven patients with suspected infection of the sternoclavicular joints
      were evaluated with spiral CT using narrow collimation (4 mm) and close interscan
      reconstruction (2-4 mm). All patients were scanned immediately following the
      injection of 120 ml Omnipaque-300 at a rate of 3 ml/s. Spiral CT scans were of 24
      or 32 s duration and done as single-breath-hold studies. All images were then
      filmed at soft tissue and bone settings (window width 2300, window center 270).
      In selected cases, coronal, sagittal, and/or oblique reconstruction of data was
      done for review. RESULTS: All studies were successfully completed without any
      interscan or intrascan motion. In six cases, infections of the sternoclavicular
      joint was found, including five cases of osteomyelitis of the clavicular head.
      The scans obtained during the phase of high contrast enhancement allowed
      definition of the extension into the soft tissue and muscle. Bone windows
      demonstrated subtle cortical and periosteal abnormalities. CONCLUSION: Imaging of
      the sternoclavicular joints with standard CT can be difficult due to interscan
      motion and the inability to get good data sets for reconstruction. Spiral CT with
      24- to 32-s acquisition allows high quality images enabling detection of disease
      and definition of extent of disease, thus helping to guide patient management.

PMID- 7644943
TI  - Tibial stress fracture mimicking neuroblastoma metastasis in two young children.

PMID- 7644942
TI  - Radiographic evaluation of the complications of long bone allografts.
AB  - PURPOSE: To study the long-term results of long bone allografts in patients with
      benign and malignant bone tumors. MATERIAL AND METHODS: Forty patients for whom
      full clinical and radiological information was held were investigated in order to
      assess the overall incidence of complications including fractures, nonunion,
      hardware problems, infections, and bone resorption. RESULTS: There were four
      deaths; four more patients had distant metastases and one patient had a recurrent
      chondrosarcoma. Seventeen patients (42%) had either no complications (nine
      patients) or only minor ones (eight patients). Eleven patients (27%) sustained
      fractures of either their allograft (eight patients) or of their hardware (three
      patients). Hardware problems occurred in nine patients (22.5%), six of whom had
      serious problems requiring revision. The majority of the fractures and hardware
      problems occurred in younger male patients (82%). Infection occurred in five
      patients (12.5%), two of whom required revision, while two cases were
      superficial. Dissolution of the allograft occurred in 12 patients (30%), 7 of
      whom required removal of the allograft. Ten of these 12 patients were female.
      CONCLUSION: The long-term survival of long bone allografts is not as good as
      generally reported if an adequate follow-up time period is used. Most of the
      fractures and hardware problems occurred in the younger active male patients,
      whose activities should probably be curtailed. Resorption of the allograft is
      another serious complication which appears to occur mainly in female patients and
      could possibly be controlled by chemotherapy.

PMID- 7644944
TI  - Primary malignant mesenchymoma of bone: case report, literature review, and
      distinction of this entity from mesenchymal and dedifferentiated chondrosarcoma.
AB  - The seventh case of primary malignant mesenchymoma of bone is reported. It is
      compared to the other six cases in the literature and clinicopathologic pattern
      of this entity is developed. Primary malignant mesenchymoma of bone is compared
      to mesenchymal chondrosarcoma and dedifferentiated chondrosarcoma. Differences as
      well as similarities are discussed and a more current classification scheme for
      malignant mesenchymoma of bone is proposed.

PMID- 7644945
TI  - MR diagnosis of fibrolipomatous hamartoma of nerve: association with nerve
      territory-oriented macrodactyly (macrodystrophia lipomatosa).

PMID- 7644946
TI  - Synovial chondromatosis.

PMID- 7644947
TI  - Malignant mesenchymoma of the thigh.

PMID- 7644948
TI  - Intramuscular hypertrophic scar: an unusual complication following soft tissue
      sarcoma resection.

PMID- 7644949
TI  - Diffuse pigmented villonodular synovitis of the shoulder.

PMID- 7644950
TI  - Multiple myeloma presenting as extramedullary plasmacytoma of the thyroid,
      advanced grade II-III plasmablastic type.

PMID- 7644951
TI  - The nature and distribution of the innervation of human supraspinal and
      interspinal ligaments.
AB  - STUDY DESIGN: To use fresh, human supraspinal and interspinal ligaments and
      document their innervation. OBJECTIVES: To characterize the innervation of the
      human supraspinal and interspinal ligaments. SUMMARY OF BACKGROUND DATA: The
      nature and distribution of the innervation of spinal ligaments remains unknown.
      METHODS: Sections of spinal ligaments were labeled with a fluorescent antibody
      against neurofilament proteins and observed with a confocal microscope. RESULTS:
      The ligaments were found to be well innervated. Innervation was equally
      distributed along the ligament, symmetrically distributed between left and right
      sides, and more densely distributed in the periphery. Pacinian corpuscles were
      scattered randomly, close to blood vessels, whereas Ruffini corpuscles were in
      the periphery, close to the collagen bundles. CONCLUSIONS: Human supraspinal and
      interspinal ligaments are well innervated. This innervation might form the basis
      of neurologic feedback mechanisms for the protection and stability of the spine.
      These mechanisms might also be important in the development of diseases such as
      scoliosis.

PMID- 7644952
TI  - In vivo evaluation of demineralized bone matrix as a bone graft substitute for
      posterior spinal fusion.
AB  - STUDY DESIGN: Posterior lumbar spinal fusion segments were evaluated in 9 adult
      mongrel dogs 6, 12, and 26 weeks after implantation. Four sites on each animal
      received implants consisting of demineralized bone matrix alone, demineralized
      bone matrix with allograft bone, allograft bone alone, and autograft bone. Each
      unilateral fusion spanned one motion segment with one intervening vertebral level
      left undisturbed using T13-L7. The fusions were evaluated radiographically,
      mechanically, and histologically. OBJECTIVE: The purpose of this study was to
      determine the efficacy of demineralized bone matrix as a bone graft substitute
      for stable posterior spinal fusion. SUMMARY OF BACKGROUND DATA: Posterior spinal
      fusion is a procedure commonly performed for spinal stabilization. Increasing the
      incidence and speed of stable spinal fusion is a primary goal in spinal surgery.
      Concerns have developed regarding the graft material used to induce bone healing
      at the fusion site. The advent of osteoinductive materials, such as demineralized
      bone matrix, may eliminate the need to harvest autograft bone and may circumvent
      the immunologic response and lower osteogenic potential associated with allograft
      bone. METHODS: The quality of fusion and new bone formation was evaluated
      radiographically using plain films, computed tomography, and magnetic resonance
      imaging. After the dogs were killed, each fusion segment was evaluated
      mechanically in torsion to determine stiffness and histologically to determine
      qualitative parameters of new bone formation and remodeling. RESULTS:
      Radiographic studies showed that autograft bone sites achieved stable fusion by
      26 weeks after surgery. Conversely, the demineralized bone matrix alone and with
      allograft bone demonstrated some new bone formation at 6 and 12 weeks, but did
      not achieve fusion by 26 weeks. The fusion sites of allograft bone alone showed
      minimal new bone formation at all time periods. Mechanically, the autograft
      fusion sites demonstrated torsional stability that was significantly greater than
      that of all other fusion sites at all time periods. The remaining fusion sites
      showed equivalent torsional stiffness at all time periods. Histologic analysis
      confirmed the radiographic and mechanical findings. CONCLUSIONS: The results
      indicate that demineralized bone matrix alone or with allograft bone is
      ineffective in achieving stable posterior spinal fusions.

PMID- 7644953
TI  - Role of ligaments and facets in lumbar spinal stability.
AB  - STUDY DESIGN: The issue of segmental stability using finite element analysis was
      studied. Effect of ligament and facet (total and partial) removal and their
      geometry on segment response were studied from the viewpoint of stability.
      OBJECTIVES: To predict factors that may be linked to the cause of rotational
      instabilities, spondylolisthesis, retrospondylolisthesis, and stenosis. SUMMARY
      OF BACKGROUND DATA: The study provides a comprehensive study on the role of
      facets and ligaments and their geometry in preserving segmental stability. No
      previous biomechanical study has explored these issues in detail. METHODS: Three
      dimensional nonlinear finite element analysis was performed on L3-L4 motion
      segments, with and without posterior elements (ligaments and facets), subjected
      to sagittal moments. Effects of ligament and facet (partial and total) removal
      and their orientations on segment response are examined from the viewpoint of
      stability. RESULTS: Ligaments play an important role in resisting flexion
      rotation and posterior shear whereas facets are mainly responsible for preventing
      large extension rotation and anterior displacement. Facet loads and stresses are
      high under large extension and anterior shear loading. Unlike total facetectomy,
      selective removal of facets does not compromise segmental stability. Facet loads
      are dependent on spatial orientation. CONCLUSIONS: Rotational instability in
      flexion or posterior displacement (retrospondylolisthesis) is unlikely without
      prior damage of ligaments, whereas instability in extension rotation or forward
      displacement (spondylolisthesis) is unlikely before facet degeneration or
      removal. The facet stress and displacement distribution predicts that facet
      osteoarthritis or hypertrophy leading to spinal stenosis is most likely under
      flexion-anterior shear loading. Selective facetectomy may restore spinal canal
      size without compromising the stability of the segment. A facet that is more
      sagittally oriented may be linked to the cause of spondylolisthesis, whereas a
      less transversely oriented facet joint may be linked to rotational instabilities
      in extension.

PMID- 7644954
TI  - Nerve root infiltration and sympathetic block. An experimental study of
      intraradicular blood flow.
AB  - STUDY DESIGN: The nerve root of L7 was exposed, and a clamp was applied to
      simulate radiculopathy. Intraradicular blood flow was measured at the takeoff
      point of the nerve root and at the distal to the dorsal root ganglion before and
      after nerve root infiltration with 2% lidocaine or physiological saline solution
      (control group), or sympathetic ganglion block with 2% lidocaine. OBJECTIVES: To
      investigate one of the mechanisms of the therapeutic effect of nerve root
      infiltration by assessing changes in intraradicular blood flow. SUMMARY OF
      BACKGROUND DATA: Increased intraradicular blood flow was noted both proximal and
      distal to the clamp after nerve root infiltration or sympathetic ganglion block
      with 2% lidocaine. No increase was seen after nerve root infiltration with saline
      solution. Macroscopic and microscopic examination showed that dye after nerve
      root infiltration did not spread beyond the clamped region to the proximal site.
      METHODS: Intraradicular blood flow was measured with a tissue blood flowmeter
      using the electrolytic hydrogen clearance method before and after nerve root
      infiltration with 2% lidocaine or physiologic saline solution (control group), or
      sympathetic ganglion block with 2% lidocaine. RESULTS: Increased intraradicular
      blood flow was noted both proximal and distal to the clamp after nerve root
      infiltration or sympathetic ganglion block with 2% lidocaine. No increase was
      seen after nerve root infiltration with saline solution. CONCLUSIONS: An increase
      in intraradicular blood flow is related to one of the mechanisms of the
      therapeutic effect of nerve root infiltration. This effect may be mediated by the
      sympathetic nervous system.

PMID- 7644955
TI  - The ability of computed tomography to identify a painful zygapophysial joint in
      patients with chronic low back pain.
AB  - STUDY DESIGN: A prospective cross-sectional analytic study. OBJECTIVES: To assess
      in patients with chronic low back pain whether the presence or absence of pain
      originating from the lumbar zygapophysial joints correlates with changes seen on
      computed tomography. SUMMARY OF BACKGROUND DATA: Results of studies have been
      divided as to whether or not radiologic imaging is able to predict those patients
      with pain originating from the zygapophysial joints. METHODS: Sixty-three
      patients with low back pain lasting for longer than 3 months underwent computed
      tomography and blocks of the zygapophysial joints at L5-S1, L4-L5, and L3-L4. The
      zygapophysial joints of all images were scored by three independent, masked
      radiologists. RESULTS: Interobserver agreement was poor with intraclass
      correlation coefficients of 0.34-0.66 using total joint scores for all three
      assessors. Using the results of a repeat assessment with two radiologists there
      was no statistically significant difference in joint scores between those with
      and those without pain originating from the zygapophysial joint. CONCLUSIONS:
      Computed tomography has no place in the diagnosis of lumbar zygapophysial joint
      pain.

PMID- 7644957
TI  - Trunk muscle endurance measurement. Isometric contrasted to isokinetic testing in
      normal subjects.
AB  - STUDY DESIGN: This cohort study examined a sample (n = 152) of subjects tested
      for isokinetic lumbar strength and endurance, using novel endurance measures.
      OBJECTIVES: To validate a new lumbar sagittal isokinetic endurance testing
      protocol comparing reliability in a normal subject cohort with strength test
      reliability to include presentation of a gender-specific normative database, and
      then correlating the results to a Sorenson isometric endurance protocol. SUMMARY
      OF BACKGROUND DATA: The isometric Sorenson test has been virtually the only
      validated clinical tool for lumbar extensor trunk muscle endurance testing, using
      an exercise chair and permitting the subject to maintain the trunk horizontal
      against gravity for a single timed contraction. Alternative isokinetic sagittal
      lumbar performance measurement methodology has been developed recently to measure
      trunk muscle endurance by determining declining work performance on repeated,
      reciprocal dynamic contractions. METHOD: We compared protocols, performance
      measures, normative data, and reliability for the static isometric Sorenson test
      to three different isokinetic endurance measurements: the endurance ratio, final
      fatigue ratio, and recovery ratio. Subjects were tested on a sagittal Cybex TEF
      (Lumex, Inc., Ronkonkoma, NY) unit for a strength trial followed by an endurance
      trial. Subgroups also performed reliability and isometric endurance protocols.
      RESULTS: We found an extremely low test-retest correlation for the isometric
      Sorenson trunk extension test. All test-retest correlations for the corresponding
      isokinetic endurance measures were significant and markedly higher. Extensor
      muscle performance declined more substantially on all endurance measures than
      flexors and showed more variability. In contrast, trunk strength measures were
      more reliable and less variable than corresponding endurance measures. Moreover,
      correlations between the isometric Sorenson test and the isokinetic endurance
      measures were all negative; i.e., increases in Sorenson time are moderately
      correlated to greater decline in work performance. CONCLUSIONS: Reliability of
      the Sorenson isometric endurance test is unacceptably low, showing negative
      correlations to all isokinetic endurance tests for lumbar extensors. Isokinetic
      strength and endurance tests are far more reliable than isometric tests, with
      normative data showing more consistent results from men than women. Both genders
      display more substantial fatigue (and greater variability) in extensor endurance
      compared with flexor testing. Endurance measures are identified as human
      performance cognitive constructs, and reasons for greater variability than
      usually shown by trunk strength measurements are discussed.

PMID- 7644956
TI  - The influence of trunk muscle coactivity on dynamic spinal loads.
AB  - STUDY DESIGN: Measured trunk muscle activity was employed in a biomechanical
      model to determine the influence of including or neglecting muscle coactivity on
      predicted spinal loads. OBJECTIVES: The purpose of this investigation was to
      examine the influence of muscle coactivity on spinal load. SUMMARY OF BACKGROUND
      DATA: Electromyographic patterns in the trunk musculature have demonstrated
      significant levels of cocontraction during lifting exertions. Biomechanical
      analyses of musculoskeletal loading are often mathematically constrained from
      including muscle coactivity. Models that attempt to include coactive behavior are
      complex and difficult to implement. METHODS: Electromyographic data were
      collected from five trunk muscle pairs while subjects performed dynamic lifting
      exertions. A validated, electromyographically assisted biomechanical model was
      used to compute relative muscle force, lifting moment, and spinal load. Results
      were generated and compared from analyses that included from one to five
      simultaneously active muscle pairs. RESULTS: Trunk extensor muscles generate
      lifting moments as much as 47% greater than the applied lifting moment to offset
      flexor antagonism. Analyses that neglect muscle coactivity during dynamic lifting
      exertions may underestimate spinal compression by as much as 45% and shear forces
      by as much as 70%. CONCLUSIONS: The level of coactive spinal loading is
      significantly influenced by the weight of the lifted load as well as trunk
      extension velocity. Muscle coactivity significantly influences the modeled load
      in the lumbar spine during lifting exertions and should be considered if an
      accurate measure of spinal loading of desired.

PMID- 7644958
TI  - Magnetic resonance imaging findings and their relationships in the thoracic and
      lumbar spine. Insights into the etiopathogenesis of spinal degeneration.
AB  - STUDY DESIGN: Descriptive epidemiologic study about magnetic resonance imaging
      findings in the spine. OBJECTIVES: To describe the prevalence of magnetic
      resonance imaging findings in a general population at spinal levels T6-S1, and to
      examine the relationships of these findings within each spinal level and between
      levels. SUMMARY OF BACKGROUND DATA: The prevalence of specific findings and the
      associations between findings and spinal levels can provide general insights into
      the etiopathogenesis of spinal degeneration. METHODS: Subjects consisted of 232
      men from a population sample (mean age 49.3 years). Signal intensity, disc
      bulging, disc herniation, and endplate irregularities were among 11 findings
      assessed from magnetic resonance images. RESULTS: The disc signal intensities
      were assessed to be lowest in the lumbar and middle thoracic regions. Disc
      bulging and disc height narrowing were most common in the lower levels of both
      the thoracic and lumbar regions. All magnetic resonance imaging findings except
      herniations and endplate irregularities were clearly associated with age.
      Osteophytes were most highly associated with disc bulging in levels T6-L3, and
      with endplate irregularities in the lower lumbar levels. Disc herniations were
      not consistently associated with any other findings. The disc levels that most
      highly correlated are grouped as follows: T6-T10, T10-L4, and L4-S1. CONCLUSIONS:
      With the exception of endplate irregularities and herniations, the magnetic
      resonance imaging findings appeared to be associated with the same pathogenic
      process. The interaction of mechanical factors and spinal structures varies
      between spinal levels, and the degeneration common in the lower parts of the
      thoracic and lumbar spine could be an outcome of vulnerability for torsional
      forces. Some gross guidelines for grouping findings can be drawn from disc level
      correlations.

PMID- 7644959
TI  - Morphometric evaluation of the first sacral vertebra and the projection of its
      pedicle on the posterior aspect of the sacrum.
AB  - STUDY DESIGN: This study directly measured the dimensions of the first sacral
      vertebra based on dry bony specimens. OBJECTIVES: To measure the dimensions of
      the S1 pedicle, vertebral body, and spinal canal, and determine the projections
      of the S1 pedicle on the posterior aspect of the sacrum. SUMMARY OF BACKGROUND
      DATA: Sacral screw fixation remains a challenging clinical problem because of the
      unique anatomy of the first sacral vertebra. The anatomic data of S1 have rarely
      been described in the literature. METHODS: Sacrums from 50 carefully prepared
      bony spines were used. Linear measurements included the dimensions of the
      vertebral body, spinal canal, and pedicle. Pedicle width was measured in two
      segments, pedicle zones 1 and 2. Angular measurements of the pedicle relative to
      the sagittal plane were also included. RESULTS: In pedicle zone 1, the average
      medial angle of the pedicles was 10.2 degrees for men and 10.7 degrees for women,
      average width was 10.9 mm for men and 10.4 mm for women, average length of the
      pedicles was 34.6 mm for men and 34.9 mm for women. In pedicle zone 2, the
      average medial angle of the pedicles was 39.4 degrees for both men and women,
      average width was 15.6 mm for men and 14.7 mm for women, average length of the
      pedicles was 43.7 mm for men, and 41.7 mm for women. The projections of pedicle
      zones 1 and 2 on the posterior aspect of S1 were determined. CONCLUSIONS: The
      investigators proposed the concept of pedicle zones 1 and 2. The safer area for
      S1 pedicle screw insertion was found in pedicle zone 2.

PMID- 7644961
TI  - Manipulative therapy versus education programs in chronic low back pain.
AB  - STUDY DESIGN: A randomized trial was conducted on a representative sample of
      patients with untreated low back pain lasting 7 weeks or longer, or having more
      than 6 episodes in 12 months. OBJECTIVES: To contrast the effectiveness of
      manipulation, a manipulation mimic, and a back education program. Methodologic
      criticisms of earlier studies were addressed. SUMMARY OF BACKGROUND DATA:
      Published meta-analyses suggest clinical benefit from manipulation for acute
      patients. Data are inconclusive for patients having symptoms for longer than 1
      month. METHODS: A total of 1267 consecutive patients were screened. Block
      randomization was used to assign 209 qualifying patients to treatment groups.
      Self-reported pain and activity tolerance served as primary outcome measures.
      Patients were assessed at enrollment, after 2 weeks of treatment, and again after
      2 weeks without treatment. Multiple teams conducted recruitment, randomization,
      assessment, treatment, and data analysis independently without sharing
      information. Treatments were carefully described, monitored, and balanced for
      physician attention and physical contact effects. RESULTS: A total of 81.3% of
      subjects completed the study. Confounding factors and missing data were
      identified in approximately 20% of those completing the final follow-up. Analysis
      of the remaining data was carried out. A strong time effect under treatment was
      observed. Greater improvement was noted in pain and activity tolerance in the
      manipulation group. Immediate benefit from pain relief continued to accrue after
      manipulation, even for the last encounter at the end of the 2-week treatment
      interval. CONCLUSION: Time is a strong ally of the low back pain patient. In
      human terms, however, there appears to be clinical value to treatment according
      to a defined plan using manipulation even in low back pain exceeding 7 weeks'
      duration.

PMID- 7644960
TI  - A randomized trial of exercise therapy in patients with acute low back pain.
      Efficacy on sickness absence.
AB  - STUDY DESIGN: A randomized, placebo-controlled trial in which patients received
      either usual care by a general practitioner (information and analgesics), or
      placebo physiotherapy given by a physiotherapist, or exercise therapy given by a
      physiotherapist. OBJECTIVE: To assess the efficacy of exercise therapy on
      sickness absence from work in patients with acute low back pain. SUMMARY OF
      BACKGROUND DATA: Exercise therapy during the nonchronic phase of back pain is
      considered to reduce sickness absence, but this opinion is controversial.
      METHODS: Patients with acute nonspecific low back pain and a paid job were
      included for analysis. Sickness absence (number of days) was checked monthly
      during the 1-year follow-up period and compliance was also assessed. RESULTS:
      From 40 general practices 363 patients who were gainfully employed were included.
      In the exercise therapy group the percentage of patients with sickness absence
      was higher and the duration of absence was longer than in the placebo and usual
      care groups, but these differences were not significant. Indications of more
      absence in the exercise therapy group appeared to be based largely on a greater
      number of patients with absences during the first 3 months. Patients in the
      exercise group who had not reported sick at entry had more sickness absences
      during the follow-up year than patients in the usual care and placebo group. Good
      compliance did not affect the results. CONCLUSIONS: Exercise therapy for patients
      with acute low back pain does not reduce sickness absence.

PMID- 7644963
TI  - Surgical results of lumbar spinal stenosis. A comparison of patients with or
      without previous back surgery.
AB  - STUDY DESIGN: This retrospective study was designed to investigate the effects of
      previous back surgery in patients undergoing surgical procedure for lumbar spinal
      stenosis. OBJECTIVES: The authors evaluated the results of singly operated and
      repeat surgery patients operated on for lumbar spinal stenosis, and compared
      prognostic factors correlated with the results for these two groups. SUMMARY OF
      BACKGROUND DATA: Repeat back surgery is generally not as successful as a first
      operation, but few studies evaluate the effects of previous back surgery on the
      surgical outcome of patients with lumbar spinal stenosis. METHODS: The subjective
      disability of singly operated and repeat surgery patients as assessed by the
      Oswestry questionnaire was compared with clinical data and myelographic findings
      to identify factors predictive of outcome. RESULTS: The mean Oswestry score was
      31.0 for singly operated patients and 40.9 for repeat surgery patients (P =
      0.0001). The outcome was excellent-to-good in 67% of singly operated patients and
      in 46% of repeat surgery ones (P < 0.0017). Severe myelographic findings
      correlated significantly with good outcome in the singly operated group but not
      in the repeat surgery group. Coexisting disease contributed significantly to poor
      outcome in the repeat surgery group, but not in the singly operated group. The
      optimum time interval for achieving successful results from subsequent surgery is
      at least 18 months after previous surgery. In the regression analysis, the
      prognostic preoperative variables for good outcome was block stenosis on
      myelography in the singly operated patients and age over 50 years and no
      coexisting disease in the repeat surgery patients. CONCLUSIONS: Previous back
      surgery had a highly significant worsening effect on the outcome of patients
      reoperated on for lumbar spinal stenosis. Not even a very well-established
      diagnosis of lumbar spinal stenosis, as confirmed by myelography and during
      surgery, could guarantee as successful a surgical outcome in the repeat surgery
      patients as that in the singly operated patients.

PMID- 7644962
TI  - On the utility of the West Haven-Yale Multidimensional Pain Inventory.
AB  - STUDY DESIGN: Two studies evaluated the West Haven-Yale Multidimensional Pain
      Inventory. This 52-item inventory contains 12 scales divided into 3 parts: 1)
      interference, support, pain severity, self-control, and negative mood; 2)
      punishing responses, solicitous responses, and distracting responses; and 3)
      household chores, outdoor work, activities away from home, and social activities.
      OBJECTIVES: The objective of study 1 was to investigate the internal structure of
      the Multidimensional Pain Inventory and its demographic correlates. The objective
      of study 2 was to explore its external correlates (construct validity). SUMMARY
      OF BACKGROUND DATA: The Multidimensional Pain Inventory appears promising because
      of its brevity, scope, ease of administration, and initial results. Despite this,
      it has attracted very little attention in the orthopedic literature since its
      introduction nearly a decade ago. METHOD: The internal structure was examined
      using oblique multiple group confirmatory factor analysis. Demographic correlates
      were examined using discriminant analysis. The external correlates were examined
      using multiple regression and discriminant analysis. RESULTS: The items' proposed
      structure fit well except that two pairs of scales are poorly separated: 1)
      activities away from home and social activities, and 2) solicitous responses and
      distracting responses. Correlations with external criteria are meaningful.
      CONCLUSIONS: The Multidimensional Pain Inventory meets standards of reliability
      and convergent validity, and it may be an improvement over current psychometric
      devices used to this same end.

PMID- 7644964
TI  - Gelfoam-induced acute quadriparesis after cervical decompression and fusion.
AB  - STUDY DESIGN: Case report. OBJECTIVE: To acknowledge a potential serious
      complication of Gelfoam use in enclosed space. SUMMARY OF BACKGROUND DATA: The
      gelatin sponge has been used for hemostasis in spine surgery. Its complication
      rate is very low, but it has the potential for compression of vital tissues when
      left next to the spinal cord within an enclosed space. METHOD: Case report.
      RESULTS: Retained Gelfoam sponges were found in an enclosed space next to the
      spinal cord. These expanded and compromised the spinal cord. CONCLUSION: There is
      potential for expansion of the Gelfoam sponge in enclosed spaces after spinal
      surgery. There is the possibility of neurologic compromise in these cases.
      Gelfoam should be removed.

PMID- 7644966
TI  - Nomina Anatomica requires zygapophysial and anulus fibrosus, several points are
      worthy of comment.

PMID- 7644965
TI  - Direct coronal computed tomography of the upper cervical spine.
AB  - STUDY DESIGN: The technique of obtaining direct coronal computed tomography
      images of the upper cervical spine is described. OBJECTIVES: To show the
      usefulness of this technique in demonstrating upper cervical spine lesions and to
      show that orbital (lens) radiation dosage is minimal compared with conventional
      tomography. SUMMARY OF BACKGROUND DATA: Conventional tomography is used routinely
      for assessment of the odontoid peg and upper cervical spine lesions. Direct
      coronal computed tomography for imaging the cervical spine has not been
      previously described. METHODS: Using a removable head support device, direct
      coronal images are obtained using a computed tomography scanner. The gantry tilt
      is adjusted from the scanogram. Direct comparison of orbital radiation dosages
      between computed tomography and conventional tomography is made from placement of
      thermoluminescent dosemeter chips onto a phantom. RESULTS: Direct coronal
      computed tomography provide superior demonstration of skeletal features in the
      upper cervical spine. Orbital radiation dose is negligible compared with
      conventional tomography. CONCLUSION: This technique may replace conventional
      tomography in assessing of stable upper cervical spine lesions.

PMID- 7644967
TI  - The effect of vocational rehabilitation and work incentives on helping the
      disabled-worker beneficiary back to work.
AB  - This article is the second in a series of articles that use data from the New
      Beneficiary Followup survey to analyze the work efforts of the Social Security
      Administration's Disability Insurance beneficiaries. Survival analysis techniques
      are used to determine the effect of vocational rehabilitation efforts and work
      incentive program provisions on actual work outcomes. The findings indicate that
      the demographic variables of age, gender, race, education, and marital status
      affect the tendency to return to work in the expected way. The results suggest a
      possible disincentive effect may be built into certain work incentive provisions
      of the program. The encouraging news is that the vocational rehabilitation
      efforts seem to have a positive effect on the tendency to return to work.
      Physical therapy, vocational training, general education, and job placement
      efforts all seem to increase the tendency to go back to work.

PMID- 7644968
TI  - Length of stay on the Supplemental Security Income Disability Program.
AB  - This article analyzes duration on the Supplemental Security Income (SSI)
      disability rolls prior to age 65 among children and working-age adults, based on
      a 10-year followup of 1974-82 cohorts of new awardees by utilizing monthly data
      from administrative records for 1974-92, and on statistical projections beyond
      the followup period. Although SSI means testing is responsible for a high
      proportion of early suspensions, when multiple spells are accounted for, long
      stays dominate. The estimated mean length of all first SSI spells is 5.5 years.
      It is 11.3 years for disabled children, 1.3 years for disabled adults eligible
      for both the Social Security Administration's Disability Insurance (DI) and SSI,
      and 6.4 years for adults eligible for SSI only. When multiple spells are
      accounted for, the projected mean total preretirement-age SSI disability stay
      almost doubles to 10.5 years for all awardees and increases to 26.7 years for
      children.

PMID- 7644969
TI  - Disability patterns among SSI recipients.
AB  - In December 1993, about 3.8 million persons under age 65 received Supplemental
      Security Income (SSI) payments because of a disability. More than half of these
      recipients had some form of mental disorder. In recent years, the number of
      disabled SSI recipients has climbed sharply. At the same time, there has been a
      change in the disability patterns among these recipients. The proportion of
      recipients with mental disorders, particularly those with psychiatric illness, is
      increasing steadily. Many of these recipients enter the SSI program in their
      youth and may stay in the program for many years. Similar increases and
      disability patterns in the Social Security Administration's Disability Insurance
      (DI) program imply program related causes, including recent changes to the
      disability requirements and outreach efforts. These changing disability patterns
      have implications for the size and shape of future SSI caseloads.

PMID- 7644970
TI  - The issue unresolved: innovating and adapting disability programs for the third
      era of Social Security.
AB  - The history of the Social Security programs in the United States falls into
      several distinct eras, defined by changing social, demographic, and economic
      conditions. At present the retirement component of these programs is moving into
      a stage of program maturation, which poses certain relatively well-understood
      changes to policymakers. The disability programs are also moving into the same
      set of societal conditions, but their impact is considerably more difficult to
      predict. Already disability incidence rates have experienced disturbingly large
      and poorly understood shifts. Developing a way to predict these shifts and to
      deal with the challenges that they make for existing programs is therefore a
      major priority of Social Security's current research agenda.

PMID- 7644971
TI  - Social Security Administration created as an independent agency: Public Law 103
      296.

PMID- 7644972
TI  - Role of private sector in financing social welfare programs, 1972-92.

PMID- 7644973
TI  - How to compute a retired-worker benefit.

PMID- 7644975
TI  - HIV clinical conference call series available from USPHS.

PMID- 7644974
TI  - Implants for single-tooth replacement. A clinical and experimental study on the
      Branemark CeraOne System.
AB  - The general aim of the thesis was to study single-tooth replacements with
      implants using a recently developed prosthodontic concept, CeraOne. More
      specifically, the aims were to present prosthodontic procedures and early
      clinical experiences of CeraOne, and to study the following: the acceptance and
      the rejection of referred patients, the mechanical strength of the complete
      implant post and of superstructures on the CeraOne abutment, the treatment
      outcome from an on-going prospective clinical investigation, the effect of guided
      tissue regeneration when using e-PTFE membranes in narrow alveolar ridges, and
      finally, the outcome from treatments by general practitioners (GPs) who had
      performed the complete care of the single-tooth patient. The acceptance and the
      rejection of patients were studied on 184 patients, and the conclusions were
      based on data from referral, case history, clinical examination, and therapy
      planning. External trauma, root fractures, and congenitally missing teeth were
      the main reasons for lost or missing teeth in referred patients, while anatomical
      limitations were the most frequent reasons for the rejections. The mechanical
      strength was determined after testing in an Instron universal testing machine.
      The abutment screw was shown to be the weakest link, while a satisfactory safety
      margin against fractures was observed for the metal-ceramic and the all-ceramic
      crowns. It was also shown that the all-ceramic ? crown could resist bending
      moments up to a level that was more than three times as high as the one at which
      the porcelain crown fractured. In the clinical prospective study, the results
      from treatments of 57 patients (65 implants) were reported after two years and
      from 34 patients (37 implants) after three years. Favourable survival rates were
      shown for the implants (97.3% at 3-4 years) and, as a mean, only a small bone
      loss around the implants and the adjacent teeth was observed. The conical
      implants, however, showed a higher degree of bone los in comparison to the other
      implants. The CeraOne prosthodontic concept was simple to sue because of
      prefabricated components, and favourable aesthetic and clinical short-term
      results were achieved. Problems of screw loosening and fistulas were avoided and
      the cementation of the crown and the subgingival placement of the abutment
      shoulder did not cause any soft tissue recession. Fifteen patients (20 implants)
      with a suspected need of guided tissue regeneration were selected for the study
      using e-PTFE membranes. After treatment and at the second stage surgery, it was
      shown that most of the primarily exposed implant surfaces at this time were
      covered by a newly formed tissue with signs of osteoid activity.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7644976
TI  - Misery, mendacity, morals and money.

PMID- 7644977
TI  - [So much to read, so little time to do it].

PMID- 7644978
TI  - [Anti-smoking action--a challenge for achievement of knowledge and wide
      distribution].

PMID- 7644979
TI  - [The university and internship, time to collect responsibility and resources?].

PMID- 7644980
TI  - [Indoor air pollution and pulmonary and respiratory tract diseases].

PMID- 7644981
TI  - [Children's indoor environment. A study of Norwegian dwellings].
AB  - The indoor environment was investigated in 112 Norwegian dwellings where either
      healthy children or children with asthma were living. Compared with the official
      guidelines for indoor air quality, more than 50% of the children's rooms had
      unacceptable indoor air. Continuous monitoring of carbon dioxide showed
      unacceptably high levels in 69% of the children's bedrooms at night. Levels of
      volatile organic compounds exceeded the guideline in 53% of the dwellings. More
      than 60% of the children were exposed to environmental tobacco smoke, as
      identified by nicotine in hair and cotinine in urine samples. Levels of house
      dust mites in excess of the guideline were found in 45% of the dwellings. The
      results indicated a need to improve the indoor environment in the homes of
      children.

PMID- 7644982
TI  - [Swimming-induced asthma].
AB  - Swimming is said to have low asthmogeneity especially when compared with other
      physical activities. Four young athletes who participated in heavy swimming
      exercise are reported as having symptoms of exercise-induced asthma (EIA). Three
      of them started to develop the symptoms after several years of training and had
      no former history of asthma. In the fourth, the asthma was diagnosed in childhood
      but the EIA-symptoms here exacerbated by swimming. All four experienced more
      symptoms when the air in the swimming pool was warm, or when there was a strong
      smell of chlorine. Two of the athletes reported having no symptoms when they swam
      in outdoor pools and had only minor symptoms, or none at all, when they did other
      formes of physical exercise, including running. In all four their swimming
      performance was hampered by their respiratory symptoms. Two of the swimmers
      improved when they inhaled steroids and adrenerg-beta 2 agonists, and continued
      their swimming carrier. The cases suggest that an irritant may provoke asthma
      symptoms in susceptible swimmers. Volatile compounds from chlorination of the
      pools are suspected as possible irritant agents.

PMID- 7644983
TI  - [Pregnancy, births and infants after in-vitro-fertilization in Norway, 1988
      1991].
AB  - We studied 1,165 pregnancies after in vitro fertilization in six public hospitals
      in Norway in the years 1988-91. The annual number of pregnancies increased from
      158 in 1988 to 365 in 1991. The mean number of replaced embryos was reduced from
      3.7 to 2.7. The rate of multiple births was not significantly altered in the same
      period, 24.3% were twin births and 5.7% triplet births. 19.3% of the pregnancies
      ended in abortion and 8.4% were ectopic. 782 births were registered in the
      Medical Birth Registry of Norway and compared with all other births during the
      period. Gestational hypertension, bleeding and preterm birth were observed more
      often in pregnancies after in vitro fertilization. The proportion of infants with
      very low birth weight (> 1,500 g) after in vitro fertilization was 9.7%, and
      nearly 50% of these were triplets. The relative risk of stillbirth and death
      during the first year of life, adjusted for maternal age and birth order, was 3.1
      (95% CI 2.4-4.0) and 2.3 (95% CI 1.5-3.5) for singletons alone. The proportion of
      multiple births should be reduced.

PMID- 7644984
TI  - [Twin pregnancy. Results from the periods 1987-88 and 1900-93].
AB  - All twins delivered at Aker Hospital during the years 1987-88 and 1990-93 were
      registered in this study. However, from 1990 onwards, all mothers bearing twins
      received special antenatal care after the 28th week of pregnancy. This care
      consisted of Doppler sonography of the umbilical artery and estimates of foetal
      weight by ultrasonography at each visit. Comparing the foetal outcome in the
      years 1987-88 with that in 1990-93, it was found that the perinatal mortality
      rate decreased from 5.4% to 2.2% and the Apgar score at 5 minutes of age improved
      for both twins. Ultrasound foetometry and Doppler sonography are valuable tools
      for antenatal surveillance of twin gestation.

PMID- 7644985
TI  - [Group work with children and their parents--a support after suspected sexual
      abuse in a day care center].
AB  - After alleged sexual abuse in a day care centre, 50 children were referred to the
      Department of child- and adolescent psychiatry in Trondheim. The children showed
      symptoms of emotional distress at referral. Group work was offered to the
      children and their parents. This article describes the group model used to help
      36 children and their parents, and the clinical experiences. Group work with
      children and parents may be a good alternative to individual treatment in similar
      situations.

PMID- 7644986
TI  - [Immunological research and diagnosis in gastroenterology--a review on occasion
      of two jubilees].
AB  - Norwegian immunological research in gastroenterology is well recognized
      internationally, and the European Medical Research Council Clinical Network for
      Gastroenterological Immunology is organized from Oslo. This development can be
      explained mainly by successful cooperation between clinical gastroenterology and
      laboratory-based research. A current jubilee in each of these fields may justify
      this review. It is now well documented that the gut is the largest antibody
      producing organ. A unique molecular integration exists between the local B cells
      and the secretory epithelium to facilitate external transport of dimeric IgA and
      pentameric IgM. The mucosal immune system is subjected to T-cell regulation and
      significant local alterations are observed in T- and B-cell populations, and in
      the macrophage subsets associated with several diseases of the gut. Subsequent
      functional immune deviation may largely explain mucosal pathology and indicates
      potential targets for future immunotherapeutic measures. Observations made in the
      gut mucosa of HIV/AIDS patients have contributed to greater understanding of the
      complex cellular and molecular interactions involved in mucosal immunity.

PMID- 7644987
TI  - [Brain and behavior].
AB  - The author briefly reviews the milestones in recent developments in brain and
      behaviour research. The psychological and physiological disciplines have
      developed in parallell, with mutual benefit to both areas of research. Cognitive
      models in psychology, and taxonomy based on psychological analyses, have been
      instrumental in formulating proper hypotheses in brain research. Data from brain
      and behaviour research have confirmed cognitive models and taxonomy in cognitive
      science and in ethological studies of animals. A complex, multidisciplinary and
      multi-factorial concept of a self-regulating central nervous network emerges, to
      replace earlier concepts of single neurons functioning in simple reflex chains.

PMID- 7644988
TI  - [The role of fatty acids in gene regulation. An example of an important
      nutritional factor which may influence our genes].
AB  - Regulation of gene expression by specific nutrients has become a major field of
      nutrition research. Evidence is presented showing that dietary constituents
      specifically modulate gene transcription and transcript processing. The
      peroxisome proliferator-activated receptor (PPAR) is a member of the steroid
      hormone receptor superfamily and is activated by a variety of hypolipidemic
      drugs, termed peroxisome proliferators. Several genes have been shown to contain
      elements responsive to peroxisome proliferator-activated receptor. These include
      the genes that encode the peroxisomal enzymes involved in beta-oxidation of fatty
      acids. The retinoid receptor X is required, however, for PPAR to bind to its
      responsive element. The finding that fatty acids are PPAR activators suggests
      that fatty acids or their acyl CoA-derivatives may regulate the lipid metabolism
      via this receptor.

PMID- 7644989
TI  - [Do the interns receive the supervision they are supposed to get?].
AB  - The Norwegian preregistration internship consists of 12 months duty as a house
      officer in hospitals (6 months in a surgical and 6 in a medical department)
      followed by 6 months in general practice. The survey assesses to what extent the
      intended information, supervision, feedback and internal evaluation assessment
      are offered the house officers during their hospital internship. A questionnaire
      was sent to all preregistration house officers who had recently finished their
      hospital duty, of whom 104 (78%) out of 133 responded. Half of the "medical" and
      65% of the "surgical" house officers reported that they received no introductory
      information nor supervision before attending hospital duties. Two thirds did not
      participate in an educational programme and 80% did not receive systematic
      feedback on their work. Most house officers received no evaluation of their work
      at all. Specific interventions are needed to ensure high quality clinical
      training of the preregistration house officers.

PMID- 7644990
TI  - [Is the training of interns in practical clinical skills adequate?].
AB  - In Norway the preregistration internship consists of 12 months service in
      hospitals followed by 6 months in general practice. This survey assessed to what
      extent the intended practical skills had been aquired during the hospital
      service. A questionnaire was sent to all preregistration house officers who had
      recently completed their internship. 104 out of 133 responded (78%). Most of the
      house officers reported that they had received training and instruction in basic
      medical and surgical skills. However, more than 30% received no formal
      supervision in various emergency medical skills and the reported instruction in
      gynaecological skills was even worse. The female house officers were less likely
      than their male colleagues to report that they had attained various practical
      clinical skills. There was substantial variation in skills among respondents from
      different hospitals. Further studies into the quality of the preregistration
      internship, and the value of specific interventions, seem to be justified.

PMID- 7644992
TI  - [Fishermen in Finnmark--the use of occupational medicine in the context of public
      health. A project within the Health and Unequality program in Finnmark].
AB  - In the municipality of Nordkapp the occupational health care unit is closely
      integrated with primary medicine, and is used in public health work. The article
      discusses the practical experiences of such an arrangement in relation to health
      problems among fishermen. The various types of projects presented are organised
      through cooperation between the occupational health care unit, the recipient
      enterprises and various public institutions. This way of working produces new and
      creative relationships for the primary health services. Moreover, new channels
      are being opened up towards the recipient enterprises. The whole arrangement
      furthers more solid cooperation, the health service being very well aware of the
      risk of medicalization.

PMID- 7644991
TI  - [Cerebral palsy in the light of old and new research results--in what direction
      does the pendulum swing?].
AB  - Cerebral palsy is reviewed from Little's first description of spastic diplegia in
      1843 to the results of the most recent studies. One central question concerns
      whether prenatal or perinatal causes are the most important for the development
      of cerebral palsy. Current research indicates that conditions prior to and during
      pregnancy probably play a more important role than earlier thought. For years it
      has been the belief that cerebral palsy is caused by mismanagement in the
      perinatal period. At the same time, it has been suggested that improved perinatal
      care would reduce the incidence of cerebral palsy. This has not been the case,
      and many studies indicate that, despite proper perinatal care, the incidence of
      cerebral palsy is increasing. Much research remains to be done to obtain an
      overall picture of the etiology of cerebral palsy before we can establish
      measures to prevent this complex and serious condition.

PMID- 7644993
TI  - [Smoking-free workplaces in the municipality of Nordkamp. A project within the
      Health and Unequality program in Finnmark].
AB  - The local health service has introduced a proposal to act against smoking habits
      among the employed in the municipality of Nordkapp. The health politicians have
      accepted the plan. The local council has given its approval. The article presents
      the plan and discusses the strategy of this process of preventive medicine. It
      stresses the importance of choosing the right pedagogic principles and how to put
      the plan into action. The article also shows an example of how a relatively
      conflicting political decision can be based successfully on convincing and sober
      argument by the health authorities. It is important that the health service still
      consciously follows up the matter.

PMID- 7644995
TI  - [Smoking-free environment in the Norwegian delivery institutions--where are we
      now?].
AB  - A questionnaire was sent to all 68 registered delivery units in Norway, in order
      to investigate the policy on smoking for employees and for pregnant and puerperal
      women. The response rate after one reminder was 82.3%. The main finding was that
      a majority (2/3) of Norwegian delivery units have already introduced a total ban
      on smoking for all employees, and increasingly so since 1990. Another seven
      hospital had made but not yet implemented the decision. As regards pregnant and
      puerperal women, more than half of the units had implemented a non-smoking
      policy. Information on the health hazards of smoking during pregnancy was routine
      in more than half of the units, and information on the impact of smoking on
      infants during the first year of life was given as a routine at about 1/3 of the
      units. We conclude that our results are positive, and provided that the delivery
      units continue to become smoke-free at the same rate as during the last three
      years, all Norwegian delivery units can be expected to be smoke-free for both
      pregnant and puerperal women and employees by 1997-98. Delivery units possess a
      unique opportunity to provide information on smoking and health hazards during
      pregnancy, and on risk to infants during the first years of life. This potential
      has not yet been fully utilised.

PMID- 7644996
TI  - [Genes, behavior and disease. A sceptic's view of gene mapping and gene therapy].
AB  - This paper contains four parts. The first focuses on The Human Genome Project
      (HGP). The concept of a "normal sequence" seems problematic. The second part
      reviews what is meant by "genetically-caused" and by "a (several) gene(s) for a
      trait". Genes work in concert, and it is likely that many genes together
      influence most complex traits. A difference in traits between two individuals,
      however, can be due to a difference in a single gene, as is the case for several
      thousand rare "genetic diseases". Such diseases were the original focus of gene
      therapy. Could gene therapy also be applied to more common complex traits?
      Diagnostic problems and the unsuccessful attempts to find a single gene
      difference in patients with manic depressive disorder, schizophrenia and
      Alzheimer's disease are discussed. Part three reviews future genetic research
      into complex traits and what kind of treatment can realistically be expected. It
      is concluded that improved diagnostics is the most likely outcome, not therapy.
      Part four raises arguments from the emerging Darwinian approach to medicine and
      states that it is far too early to even think of gene therapy. The needed
      knowledge about genes, behaviour and disease will not come from the one-sided
      genetic effort represented by HGP, and the resources should instead be invested
      in several different approaches to these complex issues.

PMID- 7644997
TI  - [The doping rules--a set of rules in good olympic spirit?].
AB  - Drug control has become a part of the everyday life of persons engaged in serious
      sport. The drug rules have also become all embrasive. A critical review
      emphasizes that both the rules and their application can threaten the legal
      rights of sportsmen, and violate ethical norms in our society. Although, the
      rules are part of the regulations of a private organization, the application of
      the rules may have social consequences reaching far beyond the responsibilities
      of the governing sports authorities. Because of the rules, many sportsmen are
      denied optimal treatment for disease and injury. For most of the drugs on the
      list of banned drugs the documentation that they enhance performance is
      insufficient or completely lacking. The information is heavily biased, and
      violates well established medical and ethical requirements. The testing, analysis
      and interpretation are all encumbered with uncertainty, which may lead to
      conviction of innocent persons. According to the opinion of the authors, there
      are substantial reasons for requiring changes in the rules in a way that takes
      care of basic principles and rights. This can only be fulfilled after an open and
      independent debate in which all involved groups--sportsmen, officials,
      politicians, and experts participate.

PMID- 7644994
TI  - [What determines smoking habits in pregnancy? A qualitative study among pregnant
      smokers].
AB  - In this article we present results from a qualitative study among 33 pregnant
      smokers, who took part in an in-depth interview in the 27th-35th weeks of
      pregnancy. The aim was to obtain insight into pregnant women's own experience of
      smoking in pregnancy. The pregnant women interviewed were concerned about their
      smoking habits. In spite of this, they still expressed positive attitudes towards
      smoking, and many did not experience pregnancy as a favourable time to stop. The
      study shows that pregnant women still lack important knowledge about the dangers
      of smoking. Pregnant smokers' attitudes towards scientific facts, and the role
      cigarettes play in their everyday lives, are considered to be important variables
      in determining smoking in pregnancy. The pregnant women experienced that their
      partner and health-personnel played a minor role in changing smoking behaviour.
      The reasons the women gave for smoking in pregnancy are discussed in the light of
      current theories on changing health behaviour. Four key questions are proposed
      which can be used by doctor and midwife to obtain knowledge of pregnant women's
      perception of the seriousness of smoking and the associated risks, and of the
      gains and barriers connected with quitting.

PMID- 7644999
TI  - [What forces direct current psychiatry?].

PMID- 7644998
TI  - [Problem-based learning--on its way into education].

PMID- 7645000
TI  - [The year of brain 1995--children's brain].

PMID- 7645001
TI  - [Minor head injuries].

PMID- 7645003
TI  - [Combination of low-molecular-weight heparin and non-steroidal anti-inflammatory
      agents].

PMID- 7645002
TI  - [The benefit of the C-reactive protein testing in possible lower respiratory
      tract infections].

PMID- 7645004
TI  - Flagellar structure in normal human spermatozoa and in spermatozoa that lack
      dynein arms.
AB  - Human sperm flagella were analyzed by electron microscopy and computer averaging
      in order to characterize normal flagella and to detect differences between normal
      and mutated spermatozoa. The A-tubules of normal spermatozoa were seen to have 13
      protofilaments and a lumen containing a 'pentagon' and a 'sickle'. The incomplete
      B-tubule was seen to have 10 protofilaments with an angular separation such that
      a complete circle would have 16 protofilaments. A thin '11th filament' is located
      at the inner border between A- and B-tubules and, in the centriole, also between
      B- and C-tubules. The tail end piece has 18 microtubules of a conventional
      appearance. We conclude that the 9 axonemal doublets split distally into 2
      microtubules and that normal microtubules with 13 protofilaments can grow from
      the incomplete B-tubules. The cell membrane in the end piece has a glycocalyx
      with regular periodicity. Spermatozoa from a man suffering from the immotile
      cilia syndrome was also analyzed. His sperm flagella were seen to be abnormal in
      that the dynein arms are lacking, and, that the sickle is incomplete. In other
      respects his immotile spermatozoa were normal; spokes and central projections
      have the same appearance as in normal spermatozoa.

PMID- 7645005
TI  - Thymic reticulum of mice. III. The connective compartment (innervation,
      vascularisation, fibrous tissues and myoid cells).
AB  - T lymphocytes interact at various levels of differentiation, with cells of the
      thymic reticulum, forming a peculiar and complex microenvironment. Following
      earlier descriptions by electron microscopy of three types of epithelial cells
      and two types of non-epithelial cells (macrophages and interdigitated cells)
      forming the thymic microenvironment, we report a study on a third compartment,
      the connective tissue, whose elements occur throughout the organ. The components
      of the capsule and trabeculae, the vascularisation and the innervation of the
      thymus and the presence of a few myoid cells are described. This is very rarely
      studied in ultrastructure. All these cells are completely imbricated and form a
      network trapping the lymphocytes, playing an essential role in the
      differentiation, maturation and selection of T cells.

PMID- 7645006
TI  - Presence of immunoreactive pro-opiomelanocortin-derived peptides and cytokines in
      the thymus of an anuran amphibian (Rana esculenta).
AB  - Pro-opiomelanocortin (POMC)-derived peptide [adrenocorticotropic hormone (ACTH),
      beta-endorphin, alpha-melanocyte-stimulating hormone (MSH)]- and cytokine (IL-1
      alpha, IL-1 beta, IL-2, IL-6, TNF-alpha)-like molecules were demonstrated in PAS
      positive epithelial cells of the thymus of the anuran amphibian Rana esculenta by
      an immunocytochemical procedure. Three groups of PAS positive epithelial cells
      were identified in subcapsular cortex, inner cortex and medulla, respectively.
      The cells containing ACTH-, alpha-MSH- and cytokine-like molecules were
      distributed in the cortex and those containing beta-endorphin-like molecules in
      the medulla and inner cortex. Thymic lymphocytes were always negative for POMC
      derived peptides and cytokines. These results suggest that the neuroendocrine
      function of the thymus can be traced back to lower vertebrates.

PMID- 7645007
TI  - Immunohistochemical analysis of proliferation and differentiation in organotypic
      cultures of cervical tumor cell lines.
AB  - Researchers have previously demonstrated that organotypic cultures of cervical
      tumor cell lines exhibit morphological characteristics similar to the in vivo
      biopsies from which they were derived (Rader et al., 1990). Both the in vivo
      biopsy and organotypic culture appeared undifferentiated. We have extended these
      studies with immunohistochemical analysis using the proliferation and
      differentiation markers, proliferating cell nuclear antigen (PCNA) and
      involucrin, respectively, to evaluate in more detail the ability of cervical
      tumor cell lines to differentiate in organotypic culture. An HPV-immortalized
      keratinocyte cell line, PE-4, expressed PCNA in the lower half and involucrin in
      the upper half of the organotypic culture which is consistent with the
      characteristics of a preneoplastic lesion in vivo. The CC-1 cell line, derived
      from an invasive squamous cell carcinoma, appeared undifferentiated, but
      expressed involucrin in the upper half of the organotypic culture. This is the
      first observation of expression of a differentiation marker in an organotypic
      culture of a cervical tumor cell line. The other cervical tumor cell lines, SiHa
      and HeLa, derived from a squamous cell carcinoma, and an adenocarcinoma of the
      cervix, respectively, did not express detectable levels of involucrin or mucin.
      All three cervical tumor cell lines, CC-1, SiHa and HeLa, expressed PCNA
      throughout their entire thickness. The majority of nuclei in SiHa and HeLa
      cultures were PCNA-positive, while the CC-1 cell line exhibited a lower growth
      fraction.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7645008
TI  - Structural study on the appearance of innervation in the stomach of mouse and rat
      embryos.
AB  - The stomach of developing embryos was examined by light and electron microscopy
      on specimens taken at each embryonic day from 11 to 17 (rat) and from 10 to 16
      (mouse). The aim of the study was to determine when the precursor cells of
      enteric neurons and endocrine cells colonize the stomach and when they begin to
      express morphologic features of mature cells. The findings show that the elements
      of the enteric nervous system are recognizable and functionally mature prior to
      the appearance of morphologically detectable gut epithelial endocrine cells. Some
      aspects of neuronal differentiation in the wall of the stomach are also
      discussed.

PMID- 7645009
TI  - Immunoelectron-microscopic study of G-protein distribution in photoreceptor cells
      of the cephalopod Sepia officinalis.
AB  - Previous studies suggest that more than one single light-stimulated transduction
      pathway seems to be present in photoreceptor cells of invertebrates. Accordingly,
      more than one light-dependent G-protein has been detected in squid photoreceptor
      cells. Two different antibodies were used to locate the distribution of G
      proteins in Sepia photoreceptors. One antiserum (anti-G alpha-common) has been
      raised against the peptide CGAGESGKSTIVKQMK. This sequence is found in most G
      alpha-protein subunits, it is also present in transducin of vertebrates. This
      sequence however, is conserved only partially in G alpha q from photosensory
      membranes of the squid. The second antiserum (anti-G alpha q) has been raised
      against the peptide QLNLKEYNLV. This sequence is present at the C-terminus of
      e.g. G alpha q from mouse brain and is identical also in squid. Anti-G alpha q
      very strongly interacted with the rhabdomeres of the photoreceptor cells from
      Sepia. In the non-rhabdomeric cytoplasm of the photoreceptor cells gold granules
      (bound to the second antibody) were almost absent. With anti-G alpha-common, only
      a small number of gold particles could be found at the rhabdomeres. The non
      rhabdomeric cytoplasm was not labelled. Thus, further G-proteins that might be
      involved in a light dependent phototransduction mechanism besides the
      phosphoinositide pathway can hardly be expected to belong to the group of
      'common' G-proteins.

PMID- 7645010
TI  - Differential distribution of glutamylated tubulin in the flagellum of mouse
      spermatozoa.
AB  - Using a monoclonal antibody (GT 335) we previously demonstrated that
      glutamylation is a predominant posttranslational modification of alpha and beta
      tubulin isoforms in the axoneme of mouse spermatozoa (Fouquet et al., Cell Motil.
      Cytoskel. 27, 49, 1994). However, we noted that the staining intensity and/or
      distribution of glutamylated tubulin were not identical using either indirect
      immunofluorescence (IIF) or immunoelectron microscopy. To test this discrepancy
      various permeabilization procedures were performed for IIF: methanol or acetone
      alone or in combination, including freezing pretreatment and with or without
      paraformaldehyde fixation. Each procedure gave a particular labeling of sperm
      axoneme. The diversity of axoneme labeling in mouse spermatids and spermatozoa
      appeared dependent both on the absence or presence of periaxonemal sheaths and
      permeabilization procedures. For comparison with IIF and to avoid problematic
      premeabilization treatments a quantitative postembedding immunogold approach was
      preferred. In these conditions the labeling predominated in the middle piece of
      the sperm flagellum and decreased progressively in the principal piece. However,
      the labeling of the terminal piece was similar to that of the middle piece. These
      results suggested a differential glutamylated tubulin distribution along the
      axoneme of the mouse sperm flagellum.

PMID- 7645011
TI  - Analysis of tissue organization by microinjection of follistatin into early
      Xenopus laevis embryos.
AB  - Xenopus laevis embryos injected with follistatin developed abnormally with
      enlarged anterior structures and defective tails. Histological sections reveal
      that these follistatin treated embryos contain large amount of notochordal tissue
      that fails to elongate. Embryonic responses to follistatin are dose and stage
      specific. These results suggested that follistatin contributes to body axis
      formation, with its most visible effect on notochord formation.

PMID- 7645012
TI  - An ultrastructural study of brown adipose tissue in pre-term human new-borns.
AB  - The ultrastructure of brown adipose tissue (BAT), the thermogenic type of adipose
      tissue, was investigated in biopsies from 4 pre-term human new-borns delivered at
      25-27 week's gestational age and compared with peri-renal brown fat from 2 adult
      patients with phaeochromocytoma (a condition of brown fat activation). The cell
      size of brown adipocytes was smaller in pre-term new-borns than in adult
      patients; adipocytes were almost exclusively multilocular, suggesting active
      thermogenesis. In 3 of the pre-term new-borns, brown adipocyte ultrastructure
      indicated a good to high degree of differentiation (in particular at the level of
      mitochondria) as compared with activated brown fat cells found in adult patients;
      in one pre-term infant the tissue morphology was obviously suggestive of an
      earlier, proliferative phase of development and the differentiation process of
      brown adipocytes could be traced in some detail. The results suggest that (a)
      brown adipose tissue may be fairly well-differentiated and thermogenetically
      active in pre-term human new-borns weighing about 750 g at birth; (b) brown
      adipocytes apparently develop from vessel-associated cells, the early signs of
      adipocyte differentiation being glycogen and lipid accumulation; (c) the
      ultrastructural morphology of mitochondria of mitochondria in well-differentiated
      BAT from pre-term infants can strictly resemble that found in active brown
      adipose tissue of adult phaeochromocytoma patients.

PMID- 7645013
TI  - Applying simulation modeling to problems in toxicology and risk assessment--a
      short perspective.
AB  - The goals of this perspective have been to examine areas where quantitative
      simulation models may be useful in toxicology and related risk assessment fields
      and to offer suggestions for preparing manuscripts that describe these models. If
      developments in other disciplines serve as a bell-wether, the use of mathematical
      models in toxicology will continue to increase, partly, at least, because the new
      generations of scientists are being trained in an electronic environment where
      computation of all kinds is learned at an early age. Undoubtedly, however, the
      utility of these models will be directly tied to the skills of investigators in
      accurately describing models in their research papers. These publications should
      convey descriptions of both the insights obtained and the opportunities provided
      by these models to integrate existing data bases and suggest new and useful
      experiments. We hope these comments serve to facilitate the expansion of good
      modeling practices as applied to toxicological problems.

PMID- 7645014
TI  - The mechanism underlying the cardiotoxic effect of the toxin from the jellyfish
      Chironex fleckeri.
AB  - We have investigated the mechanisms underlying the cardiac effects of the toxin
      from the box jellyfish Chironex fleckeri. Papillary muscles isolated from the
      hearts of ferrets and ventricular myocytes isolated from the hearts of ferrets
      and rats were used. Force, intracellular [Ca2+], and membrane potential were
      monitored in the papillary muscles; contraction, intracellular [Ca2+],
      intracellular [Na+], and membrane currents were monitored in the isolated
      myocytes. Application of the toxin to these preparations resulted in a large
      increase in intracellular [Ca2+] and the adverse symptoms of Ca2+ overload
      (aftercontractions, spontaneous contractions, a decrease in developed force, and
      an increase in resting force). The response of papillary muscles to the toxin was
      not inhibited by blockers of Ca2+ or Na+ channels or by inhibitors of the
      sarcoplasmic reticulum, Na+/K+ ATPase, or Na+/H+ exchange. The response to the
      toxin was, however, blocked by prior exposure to a solution which contained no
      Na+ and by Ni2+. In the isolated myocytes, as well as an increase in
      intracellular [Ca2+], the toxin also caused an increase in intracellular [Na+]
      and the appearance of a current which was inward at negative potentials and
      reversed at about -10 mV. These data can be explained by the toxin increasing Na+
      influx into the cell. The increase in intracellular [Na+] will then increase
      intracellular [Ca2+] via the Na+/Ca2+ exchange mechanism, thus producing the
      observed Ca2+ overload.

PMID- 7645015
TI  - The effects of fumonisin B1 on several markers of nephrotoxicity in rats.
AB  - Rats were injected intraperitoneally with saline or fumonisin B1 (FB1) at doses
      of 7.5 and 10.0 mg FB1/kg for 4 days. For each day of dosing, 24-hr urine samples
      were collected and analyzed for creatinine and protein content and the enzymes
      gamma-glutamyl-transpeptidase, lactate dehydrogenase, and N-acetyl-beta-D
      glucosaminidase. Twenty-four hours after the last dose, animals were killed and
      kidneys removed for ion transport measurement and histopathology. Significant
      increases in urine volume and decreases in urine osmolality were observed in both
      FB1 dose groups. Creatinine excretion was decreased only in the 10 mg FB1/kg
      group on the final day of the study. Urine protein excretion was elevated in both
      treated groups and found to be due primarily to high-molecular-weight proteins
      indicative of increased glomerular permeability. Enzymuria, a marker of tubular
      cell damage, was also observed with increases in the urinary excretion of all
      three enzymes measured. In renal cortical slices tubular transport of the anion p
      aminohippuric acid was reduced by 75-80% and cationic transport of
      tetraethylammonium was reduced by 40% in the FB1-treated animals. While these
      results suggest significant alterations in renal function, only minor
      histopathologic changes were observed in the kidneys of both dose groups. Results
      of the present study indicate that urine volume, proteinuria, enzymuria, and ion
      transport are sensitive indicators of early FB1-induced nephrotoxicity.

PMID- 7645016
TI  - Different contributions of cytochrome P450 2E1 and P450 2B1/2 to chloroform
      hepatotoxicity in rat.
AB  - The contribution of cytochrome P450 isozymes CYP2E1 and CYP2B1/2 to chloroform
      induced hepatotoxicity taken at 18 hr after the treatment was investigated in
      rats treated with n-hexane as an inducer of CYP2E1, 2-hexanone as an inducer of
      CYP2E1 and CYP2B1/2, and phenobarbital (PB) as an inducer of CYP2B1/2. Hepatic
      damage was evaluated by gross measurement of plasma alanine aminotransferase
      activity and histopathological examination. All treatments potentiated chloroform
      induced hepatic damage. In n-hexane-pretreated rats, the damage was maximal with
      the middle dose of chloroform (0.2 ml/kg), whereas the damage increased with dose
      in rats treated with 2-hexanone or PB. The degree of hepatic damage induced with
      the three pretreatments was in the following order: n-hexane > 2-hexanone = PB
      with the middle dose of chloroform and PB >> 2-hexanone > n-hexane with the high
      dose (0.5 ml/kg); little difference among the pretreatments was seen with the low
      dose (0.1 ml/kg). These findings suggest that CYP2E1 is a low Km isoform and
      CYP2B1/2 a high Km isoform for chloroform activation. CYP2E1-dependent hepatic
      damage was characterized by ballooned hepatocytes, which were restricted to the
      centrilobular area; with CYP2B1/2, more necrotic than ballooned hepatocytes were
      seen and the necrotic hepatocytes were found not only in the centrilobular but
      also in the midzonal and periportal areas. Chloroform treatment did not affect
      the activity of N-nitrosodimethylamine N-demethylase in pretreated rats; the high
      dose increased the activity in control rats. In contrast, the high dose of
      chloroform decreased the activity of 7-pentoxyresorufin O-depentylase in all
      induced rats but not in controls. Immunoinhibition and immunoblot analyses showed
      that the high dose of chloroform induced CYP2E1 in control rats but decreased
      CYP2B1/2 in all pretreated rats. These results suggest that although both CYP2E1
      and CYP2B1/2 contribute to chloroform-induced hepatic damage, they do so quite
      differently.

PMID- 7645017
TI  - CD8 thymocytes derived from 3,3',4,4'-tetrachlorobiphenyl-exposed fetal thymi
      possess killing activity.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and its congeners such as 3,3',4,4'
      tetrachlorobiphenyl (TCB) cause immunosuppression in experimental animals and
      possibly in humans. In previous studies we found that exposure of murine fetal
      thymic organ cultures (FTOCs) to TCDD or TCB reduced the proliferative capacity
      of immature thymocytes. At the same time, the kinetics of thymocyte maturation
      was changed, and thymocyte differentiation was skewed toward CD4-CD8+
      phenotypically mature cells. Here, we analyze the biological activities of
      thymocytes generated in TCB-exposed fetal thymus to determine whether these cells
      are also functionally mature. C57BL/6 fetal thymic lobes from Day 15 of gestation
      were explanted and grown for 8 days in FTOC in the presence or absence of 3.3
      microM TCB. Then, the functions of total thymocytes or sorted subsets thereof
      were tested. We found that thymocytes from TCB-exposed lobes responded to
      stimulation by Con A or anti-CD3 and possessed cytotoxic activity upon
      cultivation in the presence of H-2 allogenic spleen cells. Further analysis
      showed that the overall cytotoxic activity of thymocytes was mainly due to the
      CD4-CD8+ cells. Our results suggest that the CD4-CD8+ cells, which are generated
      in substantially increased numbers in TCB-exposed fetal thymus, are functionally
      competent cells.

PMID- 7645018
TI  - Effects of oncogenes on the resistance to cis-diamminedichloroplatinum(II) and
      metallothionein gene expression.
AB  - Transformation of NIH3T3 cells with the ras, the sis, or the neu oncogene
      rendered cells less susceptible to cis-diamminedichloroplatinum(II). Since
      resistance to cis-diamminedichloroplatinum(II) is reported to be associated with
      increased levels of metallothionein, we examined effects of these oncogenes on
      metallothionein gene expression. NIH3T3 cells were first transfected with the
      lacZ gene whose transcription is under the control of mouse metallothionein I
      promoter and then with the ras, the sis, or the neu oncogene. The ras and the sis
      oncogenes increased beta-galactosidase activities which were induced either by
      metal (cadmium and zinc) or by glucocorticoid (dexamethasone), whereas the neu
      oncogene repressed its activity. When SV40 early promoter was used instead of
      metallothionein I promoter for the lacZ gene transcription, the beta
      galactosidase activities were not affected by metal, dexamethasone, or any of
      these oncogenes. This result was coincident with that of reverse transcription
      polymerase chain reaction that metal-induced MT I mRNA was only detected in the
      sis- or the ras-transformed cells, whereas any of these oncogenes did not affect
      the metal-induced transcription of the MT II gene. These results demonstrate that
      the ras and the sis oncogenes upregulate the metal- or glucocorticoid-induced
      transcription from metallothionein I promoter, but the neu oncogene negatively
      regulates it. Thus, resistance to the chemotherapeutic agent by oncogenic
      transformation is partly associated with the metallothionein gene expression, and
      MT I and MT II gene expressions are differently controlled by different
      oncogenes.

PMID- 7645019
TI  - Transport of inorganic phosphate in renal cortical brush-border membrane vesicles
      of cadmium-intoxicated rats.
AB  - The effect of cadmium intoxication on the renal proximal tubular phosphate
      transport system was studied in adult male Sprague-Dawley rats. Subcutaneous
      injections of CdCl2 at a dose of 2 mg Cd/kg body wt per day for 2 weeks induced
      marked polyuria, glycosuria, proteinuria, and phosphaturia, which are
      characteristics of chronic cadmium intoxication. In the renal cortical brush
      border membrane vesicles prepared from cadmium-intoxicated rats, the cadmium
      content was drastically increased and the Na(+)-dependent phosphate uptake was
      markedly attenuated. Similar results were obtained in normal membrane vesicles
      directly exposed to free cadmium. These results indicate that cadmium
      intoxication impairs the Na(+)-phosphate cotransport system in the proximal
      tubular brush-border membrane, which may lead to phosphaturia in intact animals.

PMID- 7645020
TI  - Phlorizin binding to renal outer cortical brush-border membranes of cadmium
      injected rabbits.
AB  - The effect of cadmium injection on the high-affinity phlorizin binding to renal
      outer cortical brush-border membranes was studied in rabbits. Animals received
      subcutaneous injections of CdCl2 at a dose of 3 mg Cd/kg.day for about 3 weeks.
      Brush-border membranes were isolated from renal outer cortex by Percoll gradient
      centrifugation and magnesium precipitation. Cadmium injection resulted in a
      marked increase in membrane cadmium content and decrease in Na(+)-dependent
      phlorizin binding. The latter effect was attributed to a reduction in the number
      of binding sites (N0) and not to changes in the dissociation constant (Kd).
      Similar results were observed in normal membrane vesicles directly exposed to
      cadmium in vitro. These results suggest that one mechanism of the cadmium-induced
      glycosuria is a loss of active Na(+)-glucose cotransport carrier in the proximal
      tubular brush-border membrane by direct interaction with free cadmium.

PMID- 7645021
TI  - Glutathione depletion in human T lymphocytes: analysis of activation-associated
      gene expression and the stress response.
AB  - Glutathione depletion achieved by continuous exposure of mitogen-activated human
      T lymphocytes to L-buthionine-(S,R)-sulfoximine, a specific inhibitor of gamma
      glutamylcysteine synthetase, leads to a marked inhibition of the proliferative
      response. Concanavalin A-activated T cells treated with buthionine sulfoximine
      failed to exhibit the increase in glutathione content normally observed in
      activated T cells and were depleted of cellular glutathione over 4 days of
      culture. On Day 3 of culture, DNA synthesis was inhibited by greater than 75%. In
      addition, total RNA synthesis was dramatically reduced in the glutathione
      depleted cells being inhibited by 26, 61, and 82% on Days 2, 3, and 4,
      respectively. Despite this global reduction in RNA synthesis, no specific effects
      on mRNA expression of a number of critical T cell genes required for activation
      and/or proliferation were detected. In contrast to a recent report of GSH
      depletion leading to down-regulation of ras mRNA expression in a number of
      transformed cell lines, glutathione depletion did not influence N-ras mRNA
      expression in T lymphocytes. No influence of glutathione depletion on the
      induction of histone mRNA expression was observed. However, consistent with
      previous studies on regulation of histone mRNA expression, histone transcript
      levels were reduced when DNA synthesis was markedly inhibited. A cellular stress
      response, characterized by an increase in mRNA levels of the two stress response
      genes, HSP70 and gadd 153, was evident in glutathione-depleted unstimulated
      cells. Additionally, in these cells at 48 hr, we observed a 3.5-fold increase in
      the steady-state level of mRNA encoding the catalytic subunit of gamma
      glutamylcysteine synthetase, the enzyme inhibited by buthionine sulfoximine.

PMID- 7645022
TI  - Lack of methylation of inorganic arsenic in the chimpanzee.
AB  - Most mammals methylate inorganic arsenic (As) to methylarsonic acid (MMA) and
      dimethylarsinic acid, which are rapidly excreted in the urine. Previous studies
      have shown that, in contrast to humans, all experimental animals excrete very
      little MMA. With the aim of finding an appropriate animal model for studies on
      inorganic As metabolism and toxicity, we have investigated the metabolism of As
      in two male chimpanzees after a single iv dose of [73As]arsenate (5.8 micrograms
      As/kg body wt). The initial clearance from plasma was rapid with an apparent half
      time of about 1 hr. Urine was found to constitute the major excretory pathway
      with very little excretion in the feces. About 60% of the administered 73As dose
      was excreted in the urine within 96 hr in a biphasic manner. The second phase of
      slow urinary excretion was characterized by first-order kinetics with a half-time
      of about 7 days. Upon ion-exchange chromatography of ultrafiltrated plasma and
      urine, only inorganic As could be detected, a finding confirmed by thin-layer
      chromatography. Thus, the results indicate that the chimpanzee, as previously
      shown for the marmoset monkey, but unlike all other mammals studied so far,
      including humans, is unable to methylate and detoxify inorganic As.

PMID- 7645023
TI  - In vivo induction of liver P-glycoprotein expression by xenobiotics in monkeys.
AB  - P-glycoprotein (pgp), the protein product of the multidrug resistance (mdr) gene
      family, can confer a multidrug resistance (mdr) phenotype to cells in which it is
      expressed. One member of the pgp family, pgp2, is located on the hepatocyte
      biliary pole where it may have a role in biliary excretion. Using primates we
      sought to determine if mdr gene expression and pgp levels were affected by
      xenobiotics excreted via the bile in man. Five drugs were studied in male and
      female rhesus monkeys: erythromycin, rifampicin, tamoxifen, diethylstilbesterol
      (DES), and probenecid. For each xenobiotic, with the exception of DES, an
      increase in mdr2 mRNA was observed. The results suggest that expression of mdr2
      is responsive to xenobiotics, or their metabolites, that require biliary
      excretion. We speculate that the mdr2 gene may be a member of a class of
      xenobiotic responsive genes coding for proteins that actively excrete xenobiotics
      and/or their metabolites into the bile.

PMID- 7645024
TI  - The comparative metabolism of the four pyrrolizidine alkaloids, seneciphylline,
      retrorsine, monocrotaline, and trichodesmine in the isolated, perfused rat liver.
AB  - Despite their similarity in structure, pyrrolizidine alkaloids (PAs) vary in
      their LD50s and in the organs in which toxicity is expressed. We have examined
      whether there are differences in the metabolism of certain PAs that are
      associated with these quantitative and qualitative differences in toxicity.
      Isolated rat livers were perfused with one of four PAs (seneciphylline,
      retrorsine, monocrotaline, and trichodesmine) at 0.5 mM for 1 hr, and the
      pyrrolic metabolites determined that were released into perfusate and bile or
      bound in the liver. The proportion of the PA removed by the liver varied from 93%
      for retrorsine to 55% for trichodesmine. However, trichodesmine-perfused livers
      released the greatest amount of the dehydroalkaloid into the perfusate. These
      reactive pyrrolic metabolites appear to be largely responsible for the toxicity
      of PAs. Over the course of a 1-hr perfusion, dehydroalkaloid release varied
      fourfold among the PAs examined. Seneciphylline and retrorsine significantly
      increased bile flow. Highest concentrations of PAs in bile were achieved at 30-40
      min perfusion. Conversion of dehydroalkaloid to the conjugate 7-glutathionyl-6,7
      dihydro-1-hydroxymethyl-5H-pyrrolizine (GSDHP) is a detoxification reaction.
      GSDHP release into bile varied from 80 nmol/g liver for trichodesmine to 880
      nmol/g for retrorsine. Release of the less toxic hydrolytic product of
      dehydroalkaloids, 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine, was also
      determined. Bound pyrroles in liver are probably an indication of heptatoxicity.
      At the end of perfusion these varied from 55 nmol/g for monocrotaline to 195
      nmol/g for retrorsine. The chemical form of the bound pyrroles is a 7-thioether
      conjugate of 6,7-dihydro-1-hydroxymethyl-5H-pyrrolizine. No 7,9-dithio conjugate
      was detected, indicating that only monoalkylation has been found. These
      differences in metabolic pattern reflect differences in reactivity of the
      initially formed dehydroalkaloid and can account for the toxicological
      differences between the parent PAs.

PMID- 7645025
TI  - In utero 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) alters reproductive
      morphology and function in female rat offspring.
AB  - Exposure to pesticides or toxic substances that disrupt the endocrine system
      during sex differentiation can permanently alter reproductive function and
      produce morphological pseudohermaphrodism. While some developmental toxicants
      affect either the male or the female, in utero exposure to 0.5 micrograms
      TCDD/kg/day from Gestational Day (GD) 6 to GD 15 induces infertility in both
      sexes (K.S. Khera and J.A. Ruddick, Chlorodioxins--Origins and Fate, pp. 70-84,
      Am. Chem. Soc., Washington, DC, 1973). Although a number studies have focused on
      the effects of a single dose of TCDD on sex differentiation of the male rat and
      hamster, the reproductive alterations that account for female-mediated
      infertility after in utero exposure to TCDD have not been described. Hence, it
      was our objective to describe the anatomical and functional reproductive
      alterations in female progeny after gestational administration of TCDD. In the
      first experiment, LE Hooded rats were given a single dose of 1 microgram TCDD/kg
      by gavage on CD 8 (i.e., a period that includes major organogenesis) or GD 15
      (i.e., a period prior to sex differentiation and a dosing regime that alters sex
      differentiation of the male LE rat). In a second experiment, Holtzman rats were
      dosed with TCDD at 1 microgram/kg on GD 15, to determine if the progeny of this
      strain displayed malformations of the external genitalia and vaginal orifice as
      did LE rats. TCDD-treated female LE offspring displayed a number of unusual
      reproductive alterations. In the GD 15 group, puberty was delayed, more than 65%
      of the female offspring displayed complete to partial clefting of the phallus,
      and 80% displayed a permanent "thread" of tissue across the opening of the
      vagina. In the GD 8 treatment group, 25% displayed partially cleft phallus and
      14% had a vaginal thread. GD 15 TCDD administration also induced a high incidence
      of malformations in Holtzman female progeny (100% clefting and 83% with a vaginal
      thread). At necropsy (> 550 days old), ovarian weight was significantly reduced
      by 23% in both rat strains. In the LE rat, vaginal and behavioral estrous
      cyclicity, estrous cycle-mediated running wheel activity, and female sexual
      behaviors at proestrus (darting and lordosis to mount ratios) were not affected
      by gestational GD 15 TCDD treatment. However, untreated stud males had difficulty
      attaining intromission and took longer to ejaculate and vaginal bleeding was
      displayed during mating by GD 15 TCDD-exposed female offspring.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7645026
TI  - Effects of ALDH2, CYP1A1, and CYP2E1 genetic polymorphisms and smoking and
      drinking habits on toluene metabolism in humans.
AB  - In this study, we evaluated the effects of ALDH2, CYP1A1, and CYP2E1 genetic
      polymorphisms and smoking and drinking habits on the toluene metabolism. The
      study subjects were 92 male workers who handle toluene in a printing factory, an
      electrical parts factory, and a painting workplace in Japan. Their exposure
      levels to toluene were monitored using the diffusion-type sampler. Benzyl alcohol
      concentrations in their blood and hippuric acid (HA) and creatinine
      concentrations in their urine at the end of a workshift were determined. The
      genotype of ALDH2 was classified into the homozygous genotype of a normal ALDH2
      gene (NN), the homozygous genotype of an inactive ALDH2 gene (DD), and the
      heterozygous genotype of normal and inactive ALDH2 genes (ND). The genetic
      polymorphism of CYP1A1 and CYP2E1 were also determined by restriction fragment
      length polymorphism (RFLP). A strong correlation between the personal exposure
      level and the urinary HA concentration was observed. Regression lines were
      calculated after being divided by the five factors, i.e., ALDH2, CYP1A1, CYP2E1,
      smoking, and drinking. The HA formation from toluene was significantly (p <
      0.001) different among the genotypes of ALDH2. The slopes of the regression lines
      decreased from NN to ND to DD in this order. The benzyl alcohol concentration in
      the blood of the DD group was significantly higher than that found in the NN and
      ND groups. This result demonstrates that ALDH2 polymorphism affects the oxidation
      of benzyl alcohol to benzoic acid. The toluene metabolism was also affected by
      CYP1A1 polymorphism. The slope for the Ile/Ile (the predominant homozygous
      allele) group was significantly lower than that for the Ile/Val (the heterozygous
      allele) and Val/Val (the rare homozygous allele) group after correction for
      creatinine. A drinking habit significantly (p < 0.05) reduced urinary HA
      concentration in the NN group. A smoking habit also significantly (p < 0.05)
      reduced urinary uncorrected HA concentration in both the NN and ND groups. In a
      multiple regression analysis, ALDH2 and the drinking habit were significantly (p
      < 0.01) associated with HA excretion after toluene exposure with and without
      correction for creatinine, and the corrected HA concentration was also
      significantly (p < 0.01) increased in the Ile/Val and Val/Val group of CYP1A1.
      The smoking habit reduced the corrected HA concentration (p < 0.05); however, the
      polymorphism in the 5'-flanking region of CYP2E1 did not affect HA appearance in
      urine.

PMID- 7645027
TI  - Characterization of metallothionein-I-transgenic mice.
AB  - A metallothionein-I-transgenic mouse strain (MT-TG) was characterized to
      determine whether they would be suitable to study the functions of this protein.
      MT-TG mice were visually indistinguishable from nontransgenic littermate
      controls, but had 10- to 20-fold higher basal levels of MT protein in pancreas,
      liver, and stomach, as well as 2- to 6-fold higher MT protein levels in other
      organs (kidney, intestine, uterus, testes, spleen, heart, and lung) than control
      mice, as determined by the Cd/hemoglobin assay. The MT-TG mice had 50% more Zn in
      liver and 300% more Zn in pancreas than control mice. Interestingly, female MT-TG
      mice have 4- to 5-fold higher MT levels in liver than those of males. To
      determine whether MT can be further increased by well-known MT inducers, control
      and MT-TG mice were given Zn (200 mumol/kg), Cd (20 mumol/kg), or diethyl maleate
      (DEM, 5 mmol/kg), and tissue MT concentrations were measured 24 hr later. MT-TG
      mice responded to MT inducers in a manner similar to control mice. The hepatic
      antioxidant components (glutathione (GSH), GSH-peroxidase, GSH-reductase, GSH S
      transferase, superoxide dismutase, DT-diaphorase, and catalase) of MT-TG mice
      were not different from those of controls. The cytochrome P450 enzymes (total
      P450, b5, NADPH cytochrome c reductase) were normal in these MT-TG mice. The
      activities of CYP1A, CYP2B, and CYP2E enzymes in MT-TG mice were also similar to
      those of controls, as determined by ethoxy- and pentoxyresorufin O-dealkylation
      and chlorzoxazone 6-hydroxylation. Thus, MT-TG mice appear to be a good model for
      studying functions of MT.

PMID- 7645028
TI  - Weanling female Sprague-Dawley rats are not sensitive to the antiestrogenic
      effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).
AB  - Investigators have shown that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) can
      inhibit certain estrogenic events in vivo and in vitro. To further investigate
      this phenomenon, the effects of estradiol (E2) alone or TCDD plus estradiol on
      several estrogen-dependent parameters were evaluated in weanling female Sprague
      Dawley rats. E2 (10 micrograms/kg/day, Postnatal Days (PND) 21 and 22) caused
      significant increases in relative uterine weight and keratinization of the
      vaginal epithelium (PND 23). E2 significantly reduced uterine estrogen receptor
      (ER) protein levels and serum FSH levels, with a trend toward reduction of ER
      mRNA levels. None of these parameters were affected by pretreatment with 20, 40,
      or 80 micrograms/kg TCDD (PND 19). Uterine progesterone receptor levels were not
      affected by E2 or TCDD in the present study. In contrast, TCDD significantly
      decreased body weight (40 or 80 micrograms/kg) by PND 21, significantly decreased
      relative thymic weights, and significantly increased relative hepatic weights
      (20, 40, and 80 micrograms/kg, by PND 23). In addition, TCDD dramatically induced
      CYPIA1 hepatic mRNA levels, indicating that TCDD was properly delivered and could
      mediate other well-documented Ah receptor-dependent events. Thus, weanling female
      Sprague-Dawley rats are not sensitive to the antiestrogenic effects of TCDD at
      doses which cause overt toxicity. The results provide evidence that the
      previously reported antiestrogenic effects of TCDD are probably species, strain,
      and age dependent.

PMID- 7645029
TI  - Reproductive effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in female
      rats: ovulation, hormonal regulation, and possible mechanism(s).
AB  - A previous study has shown that exposure of adult rats to TCDD alters estrous
      cyclicity and ovulation. To further explore the mechanisms involved we employed
      the gonadotropin-primed immature female rat model. Single doses (0.3-60
      micrograms/kg) of TCDD, dissolved in corn oil, were given orally to 22-day-old
      rats. Equine chorionic gonadotropin (eCG) (20 IU) was injected 24 hr later to
      induce follicular development. Rats were killed at various times after eCG, blood
      was collected, and ovarian weights were obtained. Serum concentrations of
      estradiol-17 beta (E2), luteinizing hormone (LH), follicle stimulating hormone
      (FSH), and prolactin (LTH) were measured by radioimmunoassay. Ovulation was
      determined 72 hr after injection of eCG by counting ova flushed from oviducts.
      TCDD reduced dose-dependently the increase in ovarian weight gain induced by eCG
      and also decreased the number of animals ovulating as well as the number of ova
      recovered; the ED50 was between 3 and 10 micrograms/kg of TCDD. The increase in
      serum E2 induced by eCG was enhanced in animals treated with TCDD. Peak serum
      levels of FSH and LH, but not of LTH, were decreased by TCDD. E2, as expected,
      decreased dramatically in control animals between 60 and 72 hr after injection of
      eCG, concomitant with a preovulatory surge in LH. This response was absent in
      TCDD-treated animals. None of these effects were related to decreased food
      consumption since they were absent in pair-fed controls. In hypophysectomized
      immature rats treated with eCG and exogenous LH the percentage of rats ovulating
      and the number of ova recovered were also significantly reduced by TCDD (10 and
      60 micrograms/kg). These results suggest that TCDD alters reproductive function
      in the immature female rat model via effects on the hypothalamic-pituitary axis
      as well as by direct effects on the ovary.

PMID- 7645030
TI  - Anabolic-androgenic steroid-induced toxicity in primary neonatal rat myocardial
      cell cultures.
AB  - Recent literature reports of myocardial infarction in athletes who self
      administer anabolic-androgenic steroid (AAS) and previous animal studies of the
      effects of AASs on the heart suggest that these drugs may be directly injurious
      to the myocardium. We have previously demonstrated that 100 microM testosterone
      cypionate (TC) inhibits all beating activity of primary neonatal rat myocardial
      cell cultures within 1 hr of exposure and causes significant LDH release by 4 hr
      of exposure, indicating a direct toxic effect of TC. The purpose of this
      investigation was to evaluate the effects of commonly abused AASs on primary
      neonatal rat myocardial cell cultures and to provide insight into early cellular
      changes that may lead to TC-induced toxicity. Significant LDH release was
      observed in 5-day-old primary myocardial cell cultures (obtained from 3-to-5-day
      old Sprague-Dawley rats) exposed to 100 microM testosterone enanthate (TE),
      testosterone propionate (TP), and oxymetholone (O) for 4 and 24 hr and in
      cultures exposed to 100 microM testosterone (T) for 24 hr. Neutral red retention
      and MTT formazan production were significantly decreased in cell cultures exposed
      to 100 microM TE, TP, and O after only 4 hr of exposure, indicating a loss of
      viability and mitochondrial activity. However, there was no effect on viability
      of cell cultures exposed for 24 hr to 100 microM of a variety of other commonly
      abused AASs. Phase-contrast microscopy revealed complete disruption of the
      monolayer in cell cultures treated with 100 microM TE, TP, and O for 4 hr.
      Treatment of fura-2-loaded myocardial cell cultures with 100 microM TC produced
      no significant changes in calcium transients or baseline calcium levels for up to
      13 min of exposure. These results indicate that O, T, TC, TE, and TP produce a
      direct toxic effect in heart cell cultures and that early (< 13 min) changes in
      calcium homeostasis are unlikely to participate in the mechanism of toxicity.

PMID- 7645031
TI  - Fumonisin B1 alters sphingolipid metabolism and disrupts the barrier function of
      endothelial cells in culture.
AB  - Fumonisins are responsible for at least two diseases of veterinary importance
      (equine leukoencephalomalacia and porcine pulmonary edema) and are carcinogenic
      for experimental animals and, perhaps, humans. They have been found to disrupt
      sphingolipid metabolism in many types of cells, including hepatocytes, neurons,
      and renal cells. In this study, endothelial cells form porcine pulmonary arteries
      were cultured on micropore filters as a model for the endothelial barrier, and
      barrier function was quantitated as the movement of albumin across the
      endothelial monolayers. Fumonisin B1 increased the amount of free sphinganine by
      20- to 30-fold within 3 hr, as expected for inhibition of sphinganine
      (sphingosine) N-acyltransferase by this mycotoxin. At 30 to 50 microM, fumonisin
      B1 doubled the rate of albumin transfer across endothelial monolayers; however,
      there was no loss of cell viability based on morphology or trypan blue exclusion.
      When 15 microM D-erythro-sphinganine was added to the cells, the rate of albumin
      transfer also doubled (after 24 hr incubation) without a loss of viability;
      however, this treatment increased the cellular level of sphinganine by > 100
      fold. Addition of 25 microM sphinganine caused even greater albumin transfer, but
      also resulted in significant cell death. These results establish that fumonisin
      B1 and D-erythro-sphinganine allow accelerated passage of macromolecules across
      the endothelium. Fumonisin B1 alters sphingolipid biosynthesis with an elevation
      of sphinganine in the cells which may, at least in part, explain the observed
      disruption of endothelial barrier function.

PMID- 7645032
TI  - beta 2-Microglobulin in transplantation.

PMID- 7645033
TI  - Mycophenolate mofetil for the prevention of acute rejection in primary cadaveric
      renal allograft recipients. U.S. Renal Transplant Mycophenolate Mofetil Study
      Group.
AB  - Mycophenolate mofetil (MMF), a new immunosuppressant that selectively inhibits
      proliferation of T and B lymphocytes, may reduce the frequency and severity of
      acute graft rejection. Acute graft rejection is the leading cause of graft loss
      in cadaveric renal transplantation. The purpose of this randomized, double-blind,
      multicenter study was to evaluate the efficacy and safety of MMF for the
      prevention of acute rejection episodes in adult patients during the first 6
      months after renal transplantation. A total of 499 patients who were to receive a
      primary cadaveric renal allograft as their first transplant were randomized to
      receive MMF 1.0 g b.i.d. (MMF 2 g treatment group), MMF 1.5 g b.i.d. (MMF 3 g
      treatment group), or azathioprine 1-2 mg/kg/day. CsA, corticosteroids, and
      antithymocyte globulin (ATGAM) were administered as part of a quadruple
      sequential induction protocol. The primary efficacy endpoint was biopsy-proven
      rejection or treatment failure (defined as graft loss, death, or premature
      withdrawal from the study for any reason) during the first 6 months after
      transplant. All enrolled patients were included in the primary analyses of
      efficacy on the basis of intent to treat. The 495 patients who received study
      drug were included in the safety and secondary efficacy analyses. Biopsy-proven
      acute rejection episodes or treatment failure occurred in 47.6% of patients in
      the azathioprine group compared with 31.1% (P = 0.0015) and 31.3% (P = 0.0021) of
      patients in the MMF 2 g and 3 g treatment groups, respectively. Time to first
      biopsy-proven rejection episode or treatment failure was significantly longer for
      MMF 2 g versus azathioprine (P = 0.0036) and MMF 3 g versus azathioprine (P =
      0.0006). First biopsy-proven rejection alone occurred in 38.0% of patients who
      received azathioprine compared with 19.8% and 17.5% of patients who received MMF
      2 g and 3 g, respectively. Patients in the azathioprine group received a greater
      number of full courses of antirejection treatment as compared with the MMF 2 g
      and MMF 3 g groups (44.5%, 24.8%, and 21.1%, respectively). The use of
      antilymphocyte agents to treat rejection was greater in the azathioprine group
      (20.1%) compared with the MMF 2 g group (10.3%) and the MMF 3 g group (5.4%). At
      6 months after transplant, graft and patient survival were similar in all 3
      treatment groups.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7645034
TI  - Deletion of spontaneous rat liver allograft acceptance by donor irradiation.
AB  - Liver transplants in rodents or pigs are often spontaneously accepted across a
      complete MHC mismatch. They induce tolerance to grafts of other organs or skin of
      liver donor strain and can even suppress ongoing rejection of heart grafts. It
      has not been established whether liver-induced tolerance is due to components of
      the liver or to passenger leukocytes within the liver. We depleted populations of
      passenger leukocytes from the transplanted liver by irradiation of the donor with
      10 Gy, followed after 7 days by transplantation of the liver. Recipients of
      livers from irradiated donors had a median survival of 16 days compared with >
      100 days for recipients of livers from normal donors. Examination of recipients
      of irradiated donor livers showed that allograft rejection was the cause of
      death. Syngeneic transplants of irradiated PVG donor to PVG recipient or of
      irradiated DA donor to DA recipient survived indefinitely. Parking of livers from
      irradiated PVG donors in normal PVG animals for 36 hr reconstituted tolerance
      when the livers were retransplanted to DA recipients. Livers from irradiated
      donors had greatly reduced passenger leukocyte numbers compared with normal or
      parked livers, with virtually complete loss of lymphocytes. These results show
      that spontaneous liver allograft acceptance is associated with populations of
      passenger leukocytes that are depleted by donor irradiation.

PMID- 7645035
TI  - Cyclosporine stimulates expression of transforming growth factor-beta in renal
      cells. Possible mechanism of cyclosporines antiproliferative effects.
AB  - CsA induces a reversible inhibition of proliferation in cultured murine proximal
      tubular cells (MCT cells) and syngeneic tubulointerstitial fibroblasts (TFB). To
      test whether this effect may be caused by endogenous synthesis and release of
      transforming growth factor-beta 1 (TGF-beta 1), a well-known inhibitor of
      mitosis, MCT cells and TFB grown in serum-free media were treated with different
      concentrations of CsA. CsA, in a dose-dependent manner in a range of 500-2000
      ng/ml, stimulated expression of TGF-beta 1 protein and steady-state mRNA levels
      in both cell lines (MCT cells: controls, 9.3 +/- 1.0; 1500 ng/ml CsA, 19.1 +/-
      6.1 pg TGF-beta 1/10(3) cells [P < 0.05 vs. controls]; TFB: controls, 5.4 +/-
      0.9; 1500 ng/ml CsA, 7.7 +/- 0.3 pg TGF-beta 1/10(3) cells; n = 6). Short-term
      daily intraperitoneal injections of CsA (40 mg/kg body weight/day) into SJL mice
      for 1 and 4 weeks also induced an increase in whole kidney levels of TGF-beta 1
      mRNA. Incubation of MCT cells and TFB with CsA in the presence of 30
      micrograms/ml of a neutralizing anti-TGF-beta 1-3 mAb partly reversed the cell
      cycle arrest induced by CsA. These data suggest that CsA-mediated intrarenal
      synthesis and release of TGF-beta 1 may play a role in the CsA-induced growth
      arrest and might therefore be relevant in the development of chronic CsA
      nephrotoxicity, which is characterized by striped fibrosis and tubular atrophy.

PMID- 7645036
TI  - Pretransplant plasma exchange or immunoadsorption facilitates renal
      transplantation in immunized patients.
AB  - Patients with preformed antibodies against HLA molecules accumulate on renal
      transplant waiting lists and have inferior graft survival compared with
      nonsensitized patients. One hundred patients were included in a program of
      pretransplant removal of antibodies by plasma exchange (n = 90) or
      immunoadsorption (n = 10) in addition to prednisolone and cyclophosphamide
      medication. After plasma exchange, the panel reactivity and the antibody titer
      were reduced in about half of the patients, and after immunoadsorption the panel
      reactivity fell in 6 of 10 patients. Of the 83 patients who received grafts, 17
      received a graft from a living donor (LD) and 66 received a graft from a cadaver
      donor (CD). Patients with a positive crossmatch against their LD were included in
      the program and were thus grafted with a recent positive, current negative
      crossmatched organ. Fifteen CD graft recipients had a pretreatment positive
      crossmatch toward their donor. No episodes of hyperacute rejection were seen. One
      and 4-year graft survival rates in LD transplants with a recent positive and
      current negative crossmatch were 77% and 64%, respectively. At 1 and 4 years,
      graft survival rates were 70% and 57% in pretreated first CD graft recipients (n
      = 27) and 61% and 47% in pretreated regrafted patients (n = 39), respectively. In
      this program, a high rate of transplantation among the sensitized patients was
      achieved. Graft survival was inferior to that seen in nonsensitized patients, but
      was comparable to graft survival in sensitized patients at other centers.

PMID- 7645037
TI  - A double-blind, placebo-controlled study of monoclonal anti-interleukin-2
      receptor antibody (BT563) administration to prevent acute rejection after kidney
      transplantation.
AB  - In a double-blind, randomized, placebo-controlled trial, BT563, a murine IgG1
      anti-IL-2R antibody, was given as a rejection prophylaxis after kidney
      transplantation. Drug-related side effects were not observed. During the 10-day
      course of BT563, no rejections (0/27) were found, whereas a rejection episode
      occurred in 7 patients (7/29) (P = 0.01) during placebo treatment. Within the
      first 4 postoperative weeks, freedom from rejection in the BT563 group and in the
      placebo group was 96% vs. 76% (P = 0.05). Due to rejection in the placebo group,
      2 grafts were lost. At 3 months, an overall rejection incidence in the BT563 and
      placebo group was found of 3/27 (11%) vs. 8/29 (28%) patients (P = 0.18).
      Infectious complications were distributed equally between the 2 groups. CMV
      disease, found in 3 placebo-treated patients, occurred after rejection treatment
      (2/3). Within the BT563 group, 1 patient lost his graft due to renal artery
      thrombosis, 2 grafts were lost as a result of technical failure, and 2 patients
      had a squamous cell carcinoma that could be treated curatively. We conclude that
      the use of the anti-IL-2R mAb BT563 effectively prevents rejection after kidney
      transplantation without increasing infectious complications.

PMID- 7645038
TI  - Influence of donor-recipient HLA-DR mismatches and OKT3 prophylaxis on cadaver
      kidney graft survival.
AB  - Previous studies from our center have shown that donor-recipient HLA-DR
      mismatches (MM), characterized by the presence of the DR antigen in the donor but
      not in the recipient or vice versa, are associated with differential effects on
      graft survival (GS): some of them are beneficial (BEN) with results similar to
      those of HLA-DR identical or compatible pairs (85% 18 months GS) and some are
      detrimental (DET) (64% 18 months GS), whereas the other MM, neither BEN nor DET
      (neutral [NEU]) yield intermediate results (78% 18 months GS). The aim of the
      present study was to update the results at a longer follow-up time and to assess
      whether they are influenced or not by prophylactic administration of anti-CD3 mAb
      (OKT3). The analysis of 234 transplantations performed from 1980 to 1994 with
      only 1 HLA-DR MM confirmed the BEN effects of HLA-DR5 in either the donor or the
      recipient and the DET effects of HLA-DR1 or -DR2 in the donor and of HLA-DR2 or 
      DRW6 in the recipient. These effects were independent of those exerted by other,
      HLA-DR not related, prognostic factors. The transplants with 1 HLA-DR MM were
      then compared with those with zero HLA-DR MM (n = 378) and 4 groups were formed
      according to 2 levels of HLA-DR MM (zero or BEN MM vs. NEU or DET MM) and
      immunosuppression (with vs. without OKT3 prophylaxis). GS at 5 years was 63% in
      the group with either zero or BEN MM as compared with 41% in the group with
      either NEU or DET MM in the absence of OKT3 prophylaxis (P < 0.02); in
      comparison, with OKT3 prophylaxis, GS at 5 years was 73% in the group with either
      zero or BEN MM as compared with 58% in the group with either NEU or DET MM (P =
      0.07). We conclude that the differential effects of HLA-DR MM on GS are still
      observed under OKT3 prophylaxis, that the effects of HLA-DR and immunosuppression
      on graft outcome are additive, and that OKT3 induction therapy is superior to
      therapy without OKT3. These observations could have important implications for
      the allocation policy and management of renal transplants.

PMID- 7645039
TI  - The impact of surgical technique on the development of graft versus host disease
      in a rat small intestinal transplant model.
AB  - The small intestine and its mesentery contain a large amount of lymphoid tissue
      that can mediate graft-versus-host disease (GVHD) in small intestinal transplant
      recipients. To assess the impact of surgical technique and the retention of the
      recipient's small intestine on GVHD intensity, 12 adult Lewis rats received
      heterotopic small bowel transplants and 12 received orthotopic small bowel
      transplants from Brown Norway donors. Twelve Lewis to Lewis heterotopic small
      bowel-transplanted animals served as the control group. All recipients were given
      cyclosporine (10 mg/kg/alternate days) subcutaneously. The parameters followed
      were: weight gain and feed intake; clinical signs of GVHD; relative spleen
      weight; popliteal lymph node enlargement assay; and histological evaluation of
      spleen, liver, skin, native intestine, and transplanted intestine. According to
      the clinical scoring system, heterotopically transplanted animals were found to
      have a more severe GVHD than the orthotopic group. There were statistically
      significant differences between the relative spleen weights of the heterotopic
      transplant group and the control group (P = 0.001, 0.004, and 0.007 on days 7,
      14, and 21, respectively) and between the heterotopic and orthotopic groups at 7
      days (P = 0.037). Lymph node enlargement assays were statistically different
      between heterotopic and orthotopic groups (P = 0.019, 0.020, and 0.007 on days 7,
      14, and 21, respectively). Histological evaluation of skin biopsy specimens also
      demonstrated that GVHD was indeed more severe in the heterotopic transplanted
      group when compared with orthotopically transplanted animals. These findings
      confirm that retention of the native small intestine in the heterotopic
      intestinal transplant model significantly increases the severity of GVHD
      following transplantation.

PMID- 7645040
TI  - Natural killer cell interaction with murine allogeneic MHC class I molecules.
AB  - Class I molecules of the MHC affect target cell sensitivity to NK cell
      repertoire. In the mouse, absence of MHC class I molecules on target cells is
      associated with an increased susceptibility to NK cell-mediated lysis, while
      syngeneic class I molecules confer protection. In contrast to the protective role
      of syngeneic class I molecules, less is known about the interaction between
      murine NK cells and allogenic class I MHC molecules. In theory, such could either
      be triggering, inert, or inhibitory. To directly address the role of allogeneic
      class I in interaction with NK cells of the mouse, a panel of polyclonal
      allogeneic murine NK cells were exposed to H-2b class I positive or negative
      target cells, and susceptibility to lysis was assessed. For all effectors
      studied, regardless of H-2 haplotype or genetic background, a preferential
      killing of class I-deficient targets was observed. This pattern was observed in
      vitro with tumor as well as lymphoblast targets, and in vivo in rapid elimination
      studies of radiolabeled tumor cells. The results demonstrate that protection from
      murine NK cell-mediated lysis can be conferred by the expression of allogeneic
      class I molecules. No evidence for a triggering effect caused by the expression
      of allogeneic class I molecules was observed. The data are discussed in relation
      to current models on NK cell/MHC class I interactions, alloreactivity mediated by
      NK cells, and the role of NK cells in allogeneic graft rejection responses.

PMID- 7645041
TI  - Human complement activation via the alternative pathway on porcine endothelium
      initiated by IgA antibodies.
AB  - The role of the classical pathway (CP) and the alternative pathway (AP) of
      complement activation in hyperacute xenograft rejection remains a matter of
      considerable debate. In addition, it is unknown whether IgG and IgA antibodies
      activate complement, although these antibodies have been found in hyperacutely
      rejected xenografts. This study was initiated to assess a possible role of the AP
      of complement activation in a pig-to-human transplantation model using fresh
      human sera and isolated antibodies with cultured porcine endothelial cells (PEC)
      as targets. IgM, IgG, monomeric IgA, and dimeric IgA (dIgA) antibodies with
      reactivity toward PEC as determined by ELISA were isolated from pooled normal
      human sera. Serum from patients with agammaglobulinemia was used as a source of
      human complement. C3 and C4 deposition on nonfixed PEC during CP (1% serum) or AP
      activation (10% serum with MgEGTA) was analyzed using an ELISA. Complement
      mediated PEC lysis was tested in a 51Cr release assay. Using normal human sera as
      the source of antibodies and complement, C3 and C4 deposition was already found
      after 10 min of incubation in the CP, whereas an increasing amount of C3 was
      found in the AP. During AP activation, no C4 deposition was observed, indicating
      that CP activation did not contribute to the observed AP-mediated C3 deposition.
      Moreover, dIgA antibodies caused deposition of C3 and not C4. Purified IgM and
      dIgA antibodies (1 mg/ml) in the presence of 10% agammaglobulinemic serum showed
      a mean specific PEC lysis of 31% and 28%, respectively. Agammaglobulinemic serum
      alone or with IgG or monomeric IgA antibodies had no detectable lytic activity.
      In conclusion, dIgA antibodies might play an additional role in pig-to-human
      xenograft rejection by activating human complement via the AP.

PMID- 7645042
TI  - Effects of MHC-encoded TAP1 and TAP2 gene polymorphism and matching on kidney
      graft rejection.
AB  - The products of TAP1 and TAP2 genes, recently mapped within the MHC class II
      region, are involved in antigen presentation by MHC class I molecules, especially
      in the transport of endogenous peptides. As for most MHC genes, a polymorphism
      has been described and the possibility that it could influence the recipient
      immune response by modulating antigen presentation in kidney transplantation has
      been tested. The aim of our study was to compare TAP1 and TAP2 gene polymorphism
      and matching in 53 couples of kidney donors and recipients without any rejection
      episodes and in 55 other couples who had experienced at least 2 acute cellular
      rejection episodes; 70 healthy individuals served as controls. Our results showed
      that allelic variant frequencies of TAP1 alleles (1A to 1C) and TAP2 alleles (2A
      to 2E), as assessed by amplification refractory mutation system-polymerase chain
      reaction, were similar among "rejection" and "no rejection" populations.
      Furthermore, there were no differences of TAP1 and/or TAP2 matching between
      donors and recipients in the 2 groups. In contrast, we showed that the recipients
      of the no rejection group were better matched with their corresponding donors for
      the HLA-DR genes than those of the rejection group. These results suggest that
      the currently described polymorphism in the limited coding region of TAP1 and
      TAP2 genes does not influence the incidence of kidney allograft rejection
      episodes and seems not to be a strong link to the adjacent DR/DQ subregion.
      Moreover, the observed increase frequency of TAP1B allele in the whole
      recipient's group as compared with controls (16.2% vs. 7.1% in the healthy
      individuals; P < 0.02) was not linked to the rejection occurrence but to the
      presence of glomerulonephritis as initial disease. Our study suggests that, in
      the clinical conditions tested, neither TAP polymorphism nor TAP matching
      influences the renal graft outcome.

PMID- 7645043
TI  - Anti-donor antibody class switching after liver transplantation.
AB  - The humoral immune response directed against donor antigens was monitored by flow
      cytometry in 17 liver transplant patients using donor leukocytes as targets.
      Overall, donor-specific antibodies developed in 15 patients; these included all 9
      patients who had experienced a biopsy-proven episode of acute rejection and 6 out
      of 8 patients who had not had an acute episode of rejection. The isotypes of the
      donor-specific antibodies in the 9 patients who had experienced an early episode
      of acute rejection were IgG in 8 patients, IgE in 8 patients, and IgA in 6
      patients; all 9 patients had IgE and/or IgA antibodies. In the 6 patients who
      showed no evidence of acute clinical rejection but nevertheless developed donor
      specific antibodies, the isotype was IgM associated in 5 of them, with an
      immunoglobulin class switching to the IgG isotype; none of these patients had
      antibodies of the IgA or IgE isotype. These results indicate that the lack of
      rejection of a liver allograft does not necessarily result from a lack of immune
      response against donor antigens. Rather, the distinct pattern of (cytokine
      dependent) immunoglobulin class switching suggests that the lack of liver graft
      rejection may be the result of an immune activation pathway distinct from that
      resulting in graft rejection.

PMID- 7645044
TI  - A case of familial amyloid polyneuropathy treated with partial liver
      transplantation using a graft from a living related donor.

PMID- 7645045
TI  - False aneurysm after transplant nephrectomy. Report of two cases.

PMID- 7645046
TI  - Post-renal transplant distal limb bone pain. An under-recognized complication of
      transplantation distinct from avascular necrosis of bone?

PMID- 7645047
TI  - Renal graft thrombosis.

PMID- 7645048
TI  - Pseudocyst of the pancreas: management options.

PMID- 7645049
TI  - Biliary sludge.

PMID- 7645050
TI  - Natural honey exerts its protective effects against ethanol-induced gastric
      lesions in rats by preventing depletion of glandular nonprotein sulfhydryls.
AB  - The role of nonprotein sulfhydryls (NP-SH) in the protective effects of honey
      against absolute ethanol-induced gastric lesions was studied in rats. Sucralfate
      and ranitidine were used as known standard gastroprotective agents. Honey orally
      and drugs orally or subcutaneously were administered to 24 h fasted rats 30 or 90
      min before oral administration of ethanol. Mucosal damage and the glandular NP-SH
      levels were measured 1 h after ethanol. Both honey and sucralfate dose
      dependently afforded protection against gastric damage and reversed the changes
      in glandular NP-SH levels induced by ethanol. Ranitidine was ineffective in this
      model. Pretreatment with indomethacin (IND) did not alter the protective effects
      of honey or the NP-SH levels, but significantly reduced the protective effects of
      sucralfate. On the other hand, pretreatment with N-ethylmaleimide (NEM)
      significantly reduced the protective effects of both honey and sucralfate and
      lowered the NP-SH levels. Combined IND and NEM treatment caused a significant
      reduction of the protective effects of honey and the NP-SH levels, but the values
      were not significantly different from those obtained with NEM alone. In contrast,
      combined IND plus NEM treatment completely abolished the protective effects of
      sucralfate and significantly lowered the NP-SH levels. Although these results
      suggest the involvement of prostaglandins (PGs) -- sensitive process in the
      protective effects of sucralfate, but honey and sucralfate (partially) share a
      common mechanisms of action in mediating the gastroprotective effects through NP
      SH sensitive processes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7645051
TI  - Peritonitis in India--a decade's experience.
AB  - Generalised peritonitis is a common and dreaded surgical emergency. Its tropical
      spectrum continues to be different from its western counterpart. The study
      represents a retrospective analysis of 250 cases of peritonitis managed
      surgically over a decade at a large referral surgical unit at New Delhi.
      Perforations of the upper gastrointestinal tract viz: duodenal ulcer, enteric
      perforations etc. constitute the majority unlike western series where lower
      gastrointestinal tract perforations predominate. Despite significant delays in
      presentation, the overall prognosis remains comparable to the western figures. A
      comparatively younger age group involved may be responsible for better outcome.

PMID- 7645053
TI  - Prognostic factors influencing outcome of surgery in acute pancreatitis.

PMID- 7645052
TI  - Percutaneous transluminal balloon angioplasty in suprahepatic IVC obstruction-
      Budd-Chiari syndrome.
AB  - Encouraging results of Transluminal Angioplasty for Budd-Chiari Syndrome due to
      obstruction of Suprahepatic inferior vena cava have been reported in the last
      decade. We present our experience with two such patients, treated with balloon
      dilatation producing dramatic clinical improvements and control of disease on
      follow-up.

PMID- 7645054
TI  - Esophageal bezoar: a rare but distinct clinical entity.
AB  - A 89 year old female patient presented with severe dysphagia and was suspected to
      have carcinoma of the esophagus. Endoscopy revealed an esophageal phytobezoar
      which passed down spontaneously after unsuccessful endoscopic extraction attempt.
      Barium swallow study revealed diffuse spasm of the esophagus. A review of English
      literature revealed only 17 previous cases of esophageal bezoar. Salient features
      of esophageal bezoars are discussed based on previous reports and the current
      case.

PMID- 7645055
TI  - Colonoscopy for unexplained lower gastrointestinal bleeding in a tropical
      country.
AB  - Two hundred and forty consecutive patients with recurrent lower gastrointestinal
      bleeding were studied by colonoscopic examination. These included 187 adults and
      53 children. The procedure was successful either in identifying the lesion or in
      excluding it up to the cecum in 216 (90% patients). The source of bleeding was
      identified in 138 (74%) adults and 43 (81%) Children. Predominant lesions in
      adults were nonspecific colitis and ulcers (58%), polyps (19%), cancer (10%),
      rectal varices (4%) and tuberculosis (3%). Juvenile polyps (77%) and nonspecific
      colitis and ulcers (23%) were the cause of bleeding in children. Both in adults
      and children, 92% of these lesions involved the left colon. Rectum and sigmoid
      colon were mainly involved. Diffuse lesions were seen when nonspecific colitis
      and ulcers were the source of bleeding. Thus colonoscopic examination was useful
      in localizing the cause of rectal bleeding and the predominant lesions were
      different from those reported in the Western hemisphere.

PMID- 7645056
TI  - Endoscope break dances while the bands play.

PMID- 7645057
TI  - Incomplete septal cirrhosis: a new entity?

PMID- 7645058
TI  - Botulinum toxin in the management of anal fissure: innovative use of a familiar
      agent.

PMID- 7645059
TI  - [Is the Danish blood transfusion service out of date?].

PMID- 7645060
TI  - [Use of molecular biology in neurology].

PMID- 7645061
TI  - [Use of blood products in Denmark in 1993. Regional differences and comparison
      with other Scandinavian and European countries].
AB  - In Denmark approximately 396,000 units of blood were collected during 1993 from
      among approximately 270,000 voluntary non-renumerated blood donors corresponding
      to about 76 donations per 100 inhabitants. Almost all units (approx. 99%) were
      fractionated into blood components in the blood banks. Approximately 16,000
      erythrocyte units were rejected due to technical errors or quality control, while
      around 37,000 erythrocyte units were discarded from stock. Only 190 units were
      transfused as whole blood. In all 327,108 SAG-M erythrocyte suspensions, 70,971
      thrombocyte concentrates, 50,161 units of fresh frozen plasma, FFP, and
      approximately 1700 kg albumin, 100% were transfused, corresponding to 63, 14 and
      10 units and 340 g per 1000 inhabitants. When compared to other Scandinavian and
      European countries, Denmark has a high consumption of erythrocyte components, FFP
      and albumin for transfusion. The reason why cannot be clarified by available
      data, but it is not unlikely that Denmark has a more liberal transfusion policy
      than the other countries. There are considerable differences within Denmark as
      regards the clinical use of blood products. Counties/regions with university
      hospitals and regional and/or national functions tend to have a relatively high
      consumption. However, no information exists on consumption related to demographic
      parameters or related to hospitals, departments or diagnoses.

PMID- 7645062
TI  - [The cell mediated immune response].
AB  - T-lymphocytes are the most important regulatory cells of the immune system and
      mediate a number of crucial effector functions. The T-lymphocyte antigen receptor
      recognises peptide antigen bound to so-called Major Histocompatibility Complex
      (MHC) molecules on the surface of the target cell. Activation of CD8-positive
      cytotoxic T-lymphocytes leads to lysis of the antigen presenting cell, whereas
      activation of CD4-positive T-helper lymphocytes results in release of regulatory
      and stimulatory cytokines. In this review, the results of recent years' research
      in the function of the cell mediated immune system is presented, followed by an
      overview of the role played by the mediated immune system in protection against
      infectious disease, cancer, or as a cause of immune-mediated pathology and
      autoimmunity.

PMID- 7645063
TI  - [10-year mortality of patients admitted to coronary units with or without
      confirmed diagnosis of myocardial infarction. A relation to anamnesis and
      diagnosis at discharge].
AB  - The ten-year mortality in patients with suspected myocardial infarction with
      (AMI) and without (non-AMI) confirmed diagnosis was evaluated in 1897 non-AMI
      patients and 1401 AMI patients who were consecutively admitted to hospital during
      The Danish Verapamil Infarction Study. The following risk factors contained
      independent prognostic information about mortality for non-AMI patients: age,
      previous AMI, sex and diabetes. In patients with AMI the risk factors were: age,
      previous AMI, clinical heart failure, diabetes and angina pectoris. When the
      diagnosis at discharge for non-AMI patients was included in the Cox-analysis,
      only the diagnoses of bronchopneumonia, musculoskeletal disorders and observation
      only of added prognostic information. We conclude that non-AMI patients are at
      high risk for mortal events in the long-term. High risk patients can be
      identified from the medical history and should be carefully evaluated regarding
      coronary artery disease at the time of discharge in order to improve the risk
      stratification, treatment and prognosis.

PMID- 7645064
TI  - [Screening for prehypoxemia with oximetry--a study of two methods].
AB  - The aim of the present study was to evaluate the validity of pulse oximetry
      screening for prehypoxaemia, to assess the agreement between pulse- and haem
      oximetry and to elucidate any influence of peripheral temperature on pulse
      oximeter measurements. A consecutive prospective study was undertaken in 91
      cardiac surgery patients still in treatment with controlled mechanical
      ventilation in the early postoperative period. We examined arterial oxygen
      tension (paO2), arterial oxygen saturation (SaO2) and pulse oximeter saturation
      (SpO2) from 657 arterial blood samples. The sensitivity of the pulse oximeter was
      0.83, the specificity 0.73, and the diagnostic specificity was 0.10, at the
      chosen level of screening. The pulse oximeter showed a tendency to underestimate
      the oxygen saturation by 0.85%. The agreement between pulse- and haem-oxymetry
      was found to be good. The authors conclude that the pulse oximeter is acceptable
      for respiratory screening in postoperative cardiac surgery. The low specificity
      and the low diagnostic specificity results in frequent false alarms. Low
      peripheral temperature (down to 25%) do not influence the validity of either
      methods.

PMID- 7645065
TI  - [Intracranial distribution of iohexol and iotrolan after cervical myelography].
AB  - Twenty-eight consecutive patients undergoing cervical myelography were examined
      with either iohexol (14) or iotrolan (14). Just before the myelography a cranial
      CT was performed and control CT (3-5 slices) examinations were performed three,
      six, 24 and 48 hours afterwards. In all 28 patients CT showed intracranial
      contrast medium distribution after cervical myelography. The contrast medium
      distributed mainly in the subarachnoid space, first to the basal cisterns and the
      insular fissures, and to the 4th ventricle. The densities in the subarachnoid
      spaces were significantly higher after iotrolan than iohexol in the basal
      cisterns three and six hours after myelography, and in the 4th ventricle. The
      subcortical density was still increasing 48 hours after iotrolanmyelography while
      the subcortical density reached the maximum 24 hours after iohexolmyelography.
      Following cervical myelography the contrast media iohexol and iotrolan distribute
      intracranially and iotrolan seems to be eliminated more slowly than iohexol.

PMID- 7645066
TI  - [Acute injection-induced injuries in drug addicts. A review of 146 consecutive
      admissions].
AB  - Admissions of drug abusers with acute soft tissue lesions at the injection site
      increased in number over the period 1985-1989. There were 146 admissions in 90
      patients. The diagnoses were: 58 superficial abscesses, 27 deep abscesses, 57
      cellulitis, one tenosynovitis, one purulent arthritis, one not further
      categorised abscess and one case of arterial spasm. The commonest location was
      the groin (25%). Serious complications occurred in 17 cases, including four
      femoral amputations due to arterial lesions. Ultrasonic examination is
      recommended before surgery if central vessels can be involved, especially in the
      groin. Sufficient microbiological examination was performed in 78 cases. There
      was a predominance of polybacterial infections (53% polybacterial, 38%
      monobacterial, 9% sterile). The most common bacteria were Streptococcus spp. with
      a preponderance of oropharyngeal bacteria, Staphylococcus aureus, and anaerobes,
      especially Bacteroides spp. Typical intestinal bacteria were rare. We recommend
      that aerobic and anaerobic culturing with susceptibility testing always be
      carried out, that primary antibacterial therapy should be with an
      antistaphylococcal agent like dicloxacillin plus metronidazole and that free
      injection paraphernalia with disinfection swabs should be made easily available.

PMID- 7645067
TI  - [Primary meningococcal arthritis caused by Neisseria meningitidis. One of the
      many manifestations of meningococcal disease].
AB  - A case of primary meningococcal arthritis in the left hip of a nineteen year-old
      female is described. The diagnosis was based on microscopical detection of Gram
      negative diplococci and a positive meningococcal antibody-test. Treatment with
      benzylpenicilline and drainage was instituted. Although she was soon
      asymptomatic, the X-ray examination showed a slight destruction of the hip joint.
      One and a half years later the X-ray findings were normal. Attention is directed
      to the broad clinical spectrum of meningococcal disease.

PMID- 7645068
TI  - [Preventive visits to physicians have positive effects among the elderly].

PMID- 7645070
TI  - [Prevention].

PMID- 7645069
TI  - [Cancer of the middle ear and the auditory meatus].

PMID- 7645071
TI  - ["The lucky pill"].

PMID- 7645072
TI  - [Surgical treatment of heart failure].

PMID- 7645073
TI  - [Dynamic cardiomyoplasty. A possible surgical treatment of heart failure].
AB  - Dynamic m. latissimus dorsi cardiomyoplasty was introduced in 1985 as a new
      surgical treatment of terminal heart failure. The latissimus dorsi muscle is
      wrapped around the heart and paced simultaneously with the heart beat in order to
      contribute to the systolic function of the failing heart. Although more than 200
      patients have received this treatment, the results show a persistent high
      perioperative mortality (16-25%). However, some patients achieve a considerable
      improvement in both survival and function, despite the fact that only a minimal
      improvement of cardiac function can be shown. The advantage of dynamic
      cardiomyoplasty is that the patient can be operated on in a stable phase. Also,
      as opposed to heart transplantation, there is no need for immunosuppression.
      Until further experimental and clinical documentation is available, dynamic
      cardiomyoplasty is not a realistic alternative to the established surgical and
      medical treatment of heart failure in Denmark.

PMID- 7645074
TI  - [Conversational therapy in general practice. The definition and use and its
      relation to psychotherapy].

PMID- 7645075
TI  - [Pregnancy and the thyroid gland].
AB  - A review of pregnancy associated normal physiological changes is thyroid function
      is given as well as guidelines for treatment of thyroid dysfunction in pregnancy.
      Maternal, foetal and neonatal thyroid dysfunction can be difficult to diagnose,
      but the treatment is well established and should be provided by a team involving
      thyroidologists, obstetricians and paediatricians.

PMID- 7645076
TI  - [Cigarette smoking and the thyroid gland].
AB  - Relevant English language articles published from 1970 through 1993 regarding the
      possible influence of cigarette smoking on the thyroid were identified through a
      MEDLINE search and manual searches of identified reports. Thiocyanate in tobacco
      smoke influences the thyroid by a competitive inhibition of iodine uptake and
      organification in the gland. Also, stimulation of the sympathetic nervous system
      by cigarette smoke and benzpyrene, another constituent of tobacco, is thought to
      influence thyroid gland function. The thyroid hormones and TSH receptor
      autoantibodies are not significantly affected by smoking. Smokers have a higher
      frequency of goitre and increased serum thyroglobulin levels, especially in
      iodine deficient areas. Graves' ophthalmopathy is strongly associated with
      cigarette smoking; the more severe the eye disease the stronger the association.
      Graves' disease without ophthalmopathy is also associated with smoking, though
      this association is weaker. The thiocyanate level in cord blood equilibrates
      completely with the level in the mother, and a reverse correlation has been
      demonstrated between birth weight and thiocyanate level in cord blood. Cigarette
      smoking induces similar changes in thyroid function in the adult and the fetus.
      No separate study has elucidated the effects of cessation of smoking. However,
      there appear to be longstanding effects induced by smoking, some of which are
      probably irreversible.

PMID- 7645077
TI  - [Peritonitis among patients treated with continuous ambulatory peritoneal
      dialysis].
AB  - A retrospective study of 51 consecutive patients treated with continuous
      ambulatory peritoneal dialysis (CAPD) during a total of 736 months is presented.
      Forty-one episodes of peritonitis were found. Thirty-three patients did not
      experience peritonitis. One patient had six episodes of peritonitis. The time to
      first and second episode of peritonitis was 487 days (16.2 months) and 1005 days
      (33.5 months) respectively. The incidence of peritonitis was 0.67 episodes per
      patient-year, and was not influenced by either sex, diabetes or previous
      abdominal surgery. The time to the first episode of peritonitis was equal in
      patients suffering from one vs two or more episodes of peritonitis. Two patients
      suffered from tunnel infection. Initial treatment with vancomysin and gentamycin
      (before knowing the results of microbiological culturing) was adequate in 90% of
      the peritonitis episodes. Sterile peritonitis was found in 12% of the cases. No
      relapse of peritonitis was observed. Six patients suffered from eleven cases of
      reinfection. An optimal surgical strategy as well as vancomycin plus gentamicin
      treatment of peritonitis are advised when a reduction in infection rates is
      required

PMID- 7645078
TI  - [Late effects of occupational organic brain damage in painters 6-8 years after
      diagnosis. Occurrence of mental and psychosomatic health problems and utilization
      of health services].
AB  - With the object of illustrating effects on health and social functions of
      occupational organic brain damage, a questionnaire study was carried out in 1986
      concerning 192 brain-damaged painters and a reference group of 341 other
      painters. The study was repeated in 1990 to elucidate effects six to eight years
      after diagnosis. In 1986 a high prevalence of mental and psychosomatic symptoms
      was found among the brain-damaged painters. The prevalence correlated with
      severity of the disease, occupational situation and social network. In 1990 the
      same level of symptoms was found. In the reference group the prevalence of
      symptoms increased from 1986 to 1990. Besides the major difference in the
      prevalence of symptoms between the two groups, the level of symptoms correlated
      to the occupational situation in both groups. Twenty-seven percent of the brain
      damaged painters were still at work in 1990. The high symptom level among the
      brain-damaged painters is considered to be chronic.

PMID- 7645079
TI  - [Iliopsoas tendinitis in athletes. Diagnosis and treatment].
AB  - Iliopsoas tendinitis is a common injury in sport. Despite of this there are only
      a few articles in the literature that deal with these injuries. The changes in
      the inflamed tendons and muscles have been difficult to determine objectively.
      The modernization of ultrasound devices has improved the methods of examination
      and made it possible to diagnose objective changes in the tendons and muscles.
      Recommendations for the treatment of acute and chronic iliopsoas tendinitis are
      given.

PMID- 7645080
TI  - [Vagal atrial arrhythmia syndrome].
AB  - A case of paroxysmal atrial fibrillation with a vagal origin is presented. The
      vagal atrial arrhythmia syndrome is characterized by episodes of atrial
      fibrillation of flutter that most often occur postprandially or during the night.
      Episodes are precipitated by mild bradycardia. They should be classified as
      "lone" atrial fibrillation, and do not tend to become chronic. A rational medical
      approach is proposed.

PMID- 7645081
TI  - [Nephrotic syndrome in familial Mediterranean fever--effect of colchicine
      therapy].
AB  - Familial Mediterranean fever (FMF) is a genetic disorder virtually restricted to
      people originating from the Middle East. It is characterized by short, self
      limiting, febrile attacks of peritonitis, synovitis, pleuritis or an erysipelas
      like erythema. Without treatment systemic amyloidosis often develops and causes
      death in renal failure, usually at an early age. Two siblings with FMF and renal
      amyloidosis are presented. One had nephrotic syndrome, the other severe
      proteinuria. Continuous colchicine treatment reverse the nephrotic syndrome and
      in both patients the proteinuria was reduced. It is concluded, that even though
      colchicine can improve severe renal amyloidosis, early diagnosis of FMF is
      crucial because continuous colchicine treatment prevents both the febrile attacks
      and the amyloidosis.

PMID- 7645082
TI  - [Family screening in medullary thyroid carcinoma].

PMID- 7645083
TI  - [Long-chain polyunsaturated fatty acids and milk substitutes].

PMID- 7645084
TI  - [Sorting the apoplexy sufferers one more time?].

PMID- 7645085
TI  - [Personality characteristics in ulcer disease].

PMID- 7645086
TI  - [Clinical databases].

PMID- 7645087
TI  - [Quality assurance in an outpatient clinic for diabetics].

PMID- 7645088
TI  - [Pre-eclampsia. Where do we stand?].

PMID- 7645089
TI  - [Nutritional assessment of recipes distributed to households].
AB  - This study examines the nutritional standards of recipes in six pamphlets
      distributed to all households in Denmark. The publications all purport to contain
      recipes for a healthy diet. The nutritional values given in the publications are
      compared to calculated values and found to be almost identical. The fat content
      of most of the recipes is too high: recipes in the first three pamphlets had a
      median fat energy content of 50%. The later publications are better: 40% in two
      pamphlet and 33% in the last pamphlet. It is likely that the high fat content of
      the household distributed pamphlets contributes to the continued high fat content
      in the Danish diet. We suggest that the fat energy percent should be less than 30
      in half the recipes and be only 30-35 on average. The energy content should not
      be greater than 2.5-3.5 MJ per portion. Nutritional value estimates and the
      nutrition information should be standardized so as to make them more accessible
      for the consumer who wishes to make healthy diet choices, and more instructive
      generally concerning general principles of an appetizing and healthy diet.

PMID- 7645090
TI  - [Fertility-promoting intervention in the Fallopian tubes--is fertility surgery
      worthwhile?].
AB  - A prospective study of 48 cases of microsurgery for infertility caused by tubal
      occlusion carried out at Odense University Hospital during the years 1989-92 is
      presented. The follow-up period was between one to five years. The overall term
      pregnancy rate was 25% and the ectopic pregnancy rate 19%. Based on a simple
      peroperative scoring system all patients could be allocated to two clearly
      separated prognostic categories with term pregnancy rates of 42% and 15% and
      ectopic pregnancy rates of 14% and 21% respectively. In accordance with other
      recent studies, this study showed that acceptable term pregnancy rates, i.e.,
      about 40-50%, were achieved by salpingolysis and fimbrioplasty/salpingostomy only
      in cases where the adhesions were few, the tubal wall normal or thin and the
      endosalpinx appeared macroscopically normal. In cases of medial
      stenosis/occlusions, irrespective of the occurrence of lateral tubal damage, the
      results are poor. The only exception to this is reversal of sterilisation. Today
      the cumulated term pregnancy rate after three IVF-attempts in the same group of
      patients is about 55-60%. If microsurgical infertility treatment is to be
      considered an option, it is imperative that the success rate is comparable to
      that of the IVF success rate. This is only to be expected with stringent
      preoperative selection using a simple scoring system. It is concluded that
      microsurgical and certainly macrosurgical treatment of infertility should be
      abandoned in the vast majority of cases.

PMID- 7645091
TI  - [Poisoning by green and white mushrooms at a special hepatology unit, 1989-1994].
AB  - In the period 1989-1994 eight patients, who were intoxicated with the mushrooms
      Amanita phalloides (death cap) or Amanita virosa (deadly agaric) were treated at
      a Department of Hepatology. All patients had had a symptom free period of more
      than eight hours before the onset of gastrointestinal symptoms; these symptoms
      lasting in many cases for several days. All patients had biochemical signs of
      hepatocellular damage and three patients developed hepatic encephalopathy,
      fulfilling the criteria for fulminant hepatic failure (FHF). Two died and one
      patient underwent successful urgent liver transplantation. ALL FHF patients had a
      prothrombin index below 10% and increased creatine. Antidote treatment with
      penicillin and silibinine should be given promptly on suspicion of Amanita
      intoxication and should not await biochemical parameters. Transferral to a
      hepatological department with access to liver transplantation should be
      considered if abnormal biochemical liver function develops.

PMID- 7645092
TI  - [Paraquat poisoning. Treatment and prognosis].
AB  - Treatment of paraquat intoxication is most often in vain if initial treatment is
      delayed. We report a case where the patient was admitted 25 hours after oral
      intake of paraquat. The patient died due to respiratory insufficiency secondary
      to peroxidative pulmonary fibrosis in spite of combined continuous haemodialysis
      and haemofiltration. Principles of treatment are reviewed.

PMID- 7645093
TI  - [Fatal pancreatitis associated with valproate therapy].
AB  - We report a fatal case of haemorrhagic pancreatic necrosis in a 15-year-old
      mentally retarded epileptic male who had been taking sodium valproate (VPA) in
      the recommended dosage for one and a half years. The patient was admitted to
      hospital because of acute abdominal pain, with nausea and vomiting. Serum amylase
      was 609 U/l (normal range 100-360 U/l). Two exploratory laparotomies were
      performed. The second revealed haemorrhagic pancreatitis with areas of necrosis.
      VPA therapy was discontinued after the second laparotomy, but the patient died 25
      days after admission. Autopsy showed extensive haemorrhagic pancreatic necrosis.
      Non-specific vomiting and abdominal pain occur frequently during VPA therapy, but
      VPA-related pancreatitis should be considered when there is severe abdominal pain
      with nausea and vomiting. Awareness of this problem and early discontinuation of
      VPA therapy may prevent serious reactions.

PMID- 7645094
TI  - [Nocardiosis in HIV patients].
AB  - Two cases of nocardiosis, an uncommon disease in HIV patients, are presented.
      Considerations concerning diagnosis, clinical pictures, treatment and prophylaxis
      are discussed. Because of profound morbidity and mortality, the possibility of
      Nocardia infection should be suspected in cases of pulmonary infection where more
      common pathogens cannot be found.

PMID- 7645095
TI  - [Schizophrenia or spiritual crisis? On "raising the kundalini" and its diagnostic
      classification].
AB  - Two patients are described who had been diagnosed as schizophrenic, but had
      actually instead been going through spiritual crises, which in Eastern spiritual
      tradition are called raising the kundalini. Perhaps this experience is not a
      disease, but many--especially if not understood by oneself, the nearest relations
      and the medical profession--cause mental illness. In WHO ICD-10 the experience
      could be classified as F48.8, disordines neurotici specificati alii. The process
      falls outside the categories of both normal and psychotic. When allowed to
      progress to completion this process culminates in deep psychological balance,
      strength, and maturity.

PMID- 7645097
TI  - [Fetuses and newborn infants exposed to Nicorette].

PMID- 7645098
TI  - [Cauda equina syndrome or only urination problems--emergency surgery?].

PMID- 7645096
TI  - [Carbon monoxide poisoning].

PMID- 7645099
TI  - [The partial cauda equina syndrome].
AB  - In order to reduce the number of patients with a complete cauda equina-syndrome
      we reviewed the records of 63 surgically treated patients with lumbar root
      compression and bladder symptoms. Patients with a complete cauda equina-syndrome
      were excluded. Twenty-seven (43%) patients were admitted to the neurosurgical
      department more than 24 hours after the onset of bladder symptoms, an
      unacceptable delay mainly due to the reluctance of the patients to seek medical
      attention. The bladder symptoms remitted completely in 61 patients (97%). In
      spite of this the partial cauda equina-syndrome can still progress to a complete
      syndrome, so we recommend that all patients receiving conservative treatment for
      a lumbar disc prolapse should be advised to seek medical attention should voiding
      problems arise.

PMID- 7645100
TI  - [Neonatal hypoglycemia--new limits for treatment?].
AB  - Neonatal hypoglycaemia is the commonest clinical manifestation af disordered
      energy metabolism and is important because sustained hypoglycaemia may cause
      neuronal damage. Infants at high risk of developing low brain energy levels are
      those who have increased metabolic demands, low glycogen reserves, insufficient
      counter-regulatory responses or hyperinsuliaemia, and there is accumulating
      evidence that blood glucose should be maintained above 2.5 mM in this group. If
      possible, early and regular feeding at a volume of 120 ml/kg/dag should be
      established, but supplementation with intravenous glucose may be necessary.

PMID- 7645101
TI  - [Incidence of alcohol abuse among patients with emergency admissions to a
      psychiatric department. Evaluation based on clinical and biochemical markers].
AB  - Alcoholism and drug abuse were investigated in psychiatric patients, who were
      acutely admitted to a general psychiatric ward at Silkeborg Hospital in Denmark
      during a six month period. Several standardized diagnostic systems and assessment
      instruments were applied: ICD-8 and DSM-III diagnoses and the WHO Alcohol Use
      Disorder Identification Test (AUDIT) and Short Michigan Alcoholism Screening Test
      (SMAST). Furthermore, several biochemical markers were studied, including
      carbohydrate-deficient-transferrin (CDT), gamma-glutamyltransferase (GGT), and S
      ethanol. Finally, thin layer chromatography of the urine was used to detect drugs
      abuse. A diagnosis of Alcoholism (code 303) was obtained in 39% of the included
      patients, while 13% were considered drug abusers (main and subsidiary diagnosis).
      These findings are in accordance with several previously published Danish studies
      and illustrate that alcohol abuse is a common diagnosis among acutely admitted
      patients to a psychiatric department situated outside the metropolitan areas in
      Denmark. When comparing alcohol abuse as assessed by clinical information and by
      biochemical markers, only CDT and GGT gave estimates similar to clinical
      evaluations. CDT was positive in 41% of the patients. Taking ICD-8 diagnoses of
      alcoholism as "golden standards" the sensitivity and specificity of the marker
      was 0.67 and 0.74, respectively. Although this is not as high as previously found
      values, these figures suggest CDT to be a useful biological marker in the
      delineation of alcohol related problems in psychiatric patients.

PMID- 7645102
TI  - [Posture-related injuries and patient insurance].
AB  - The Danish Patient Insurance Society (Patientforsikringsforeningen) was
      established by law in July 1992. The aim was to provide a just system of
      compensation for complications following medical treatment, that are not caused
      by culpous actions or omissions. The first 34 case records concerning position
      related nerve injury were reviewed. The material has national coverage. The exact
      incidence of position related nerve injury in Denmark is unknown, but transitory
      neurological symptoms after otherwise uncomplicated surgical procedures are
      probably not infrequent complications. The material includes 17 males and 17
      females. Position-related injury most often affects the peroneal nerve, followed
      by the ulnar nerve and lesions to the brachial plexus. The etiology is often
      difficult to establish precisely, and may often be multifactorial. In our
      material the main reason is believed to be direct pressure to the nerve in 76% of
      cases. Predisposition (e.g. subclinical neuropathy or diabetes) often complicates
      the case, but neurophysiological examination and the relation in time between an
      operation and the onset of neurological symptoms often clarifies the etiology.

PMID- 7645103
TI  - [Compartment syndrome as a postoperative complication of lithotomy position].
AB  - Surgical procedures necessitating the use of the lithotomy position can be
      associated with neuromuscular lesions, usually arising from compression of nerves
      and muscles. Compartment syndrome of the lower extremities is a grave
      complication which, if unrecognized, can lead to either permanent neuromuscular
      dysfunction or limb loss. We report two cases of compartment syndrome
      complicating surgery in the lithotomy position.

PMID- 7645104
TI  - [Fracture-dislocation of Chopart's junction].
AB  - Fracture dislocation of the midtarsal joint or Chopart's junction is a rare
      condition where an early recognition and treatment is needed to avoid instability
      and significant longterm foot problems. The radiological aspects are discussed
      based on two cases.

PMID- 7645105
TI  - [Infectious mononucleosis and the risk of splenic rupture].
AB  - Infectious mononucleosis is a common and benign disease, affecting mainly
      teenagers and young adults. Patients with IM are often generally advised to
      restrain from physical exertion for a period of 6 months. We report one case of
      splenic rupture in a patient with IM which required emergency laparotomy and
      splenectomy and one case of splenic rupture which was managed with conservative
      treatment. We have retrospectively examined the 37 cases of IM admitted during
      the period 1990-1994 and found that liver function tests return to normal within
      eight weeks. We therefore advise that patients with IM and no abdominal
      discomfort should limit their physical activity during eight weeks of
      convalescence. Patients with IM and abdominal pain should be further examined,
      using imaging procedures.

PMID- 7645106
TI  - [Monosymptomatic pupillary dilatation caused by scopolamine patch].
AB  - A case of monosymptomatic unilateral mydriasis caused by scopolamine patches is
      presented. The same symptom caused by pressure from an aneurysm on the oculomotor
      nerve is exceptionally rare.

PMID- 7645107
TI  - [Hepatitis B and occupational risk groups].

PMID- 7645108
TI  - [The simvastatin study--was the consumption of wine considered?].

PMID- 7645109
TI  - [Methotrexate in the treatment of asthma. An inappropriate emergency solution or
      a valuable experimental treatment?].

PMID- 7645110
TI  - [Methotrexate treatment of patients with prednisolone dependent bronchial
      asthma].
AB  - In this review we went through eight placebo-controlled clinical trials of the
      folic acid antagonist methotrexate in the treatment of bronchial asthma. The
      studies, which differ in their methods and findings, are reviewed critically.
      Some studies seem to give documentation of methotrexate as an effective drug in
      reducing the corticosteroid requirements in patients with chronic corticosteroid
      dependent asthma. Adverse effects are wellknown from the use of methotrexate in
      patients with rheumatoid arthritis and include nausea, diarrhoea, vomiting,
      transient increases in liver enzymes, alopecia and stomatitis. Rare but
      potentially life-threatening adverse effects are interstitial pneumonitis,
      opportunistic infections, bone marrow- and renal insufficiency. The role of
      methotrexate in patients with chronic corticosteroid-dependent asthma still needs
      to be clarified. Practical guide-lines in treating asthma patients with
      methotrexate are suggested.

PMID- 7645111
TI  - [Semirigid and flexible uretero-nephroscopy].
AB  - Thirty-seven ureteronephroscopies with the modern ureteroscope were attempted in
      30 patients (median age of 60 years) because of radiographic filling defects,
      tumours, stenoses, stones, broken double "J" stent, unilateral haematuria and
      surveillance. Only one ureteronephroscopy (3%) could not be performed. The
      radiographic filling defects represented tumour (ten), stones (three) and a torn
      off papilla (one). The ureteric stenoses could be classified as congenital (one),
      secondary to a vascular graft (1), tumour (1) or inflammation (two). In nine
      patients the stones were removed, and in four fragmented and the fragments passed
      during the next two to four weeks while treated with a stent. One ureteric tumour
      and two pelvis/calyx tumours were coagulated. One broken stent was removed, and
      one displaced nefrostomy catheter was caught in the calyx and pulled into the
      pelvis. There were three cases with transient fever, all in patients with
      infected nefrostomies. The modern ureteronephroscopy is a valuable method with
      only few complications.

PMID- 7645112
TI  - [Craniopharyngiomas. Neurosurgical treatment and therapeutic results].
AB  - From 1984 to 1993, 24 patients were operated for craniopharyngeoma at the
      University Clinic of Neurosurgery, Rigshospitalet, Copenhagen. We undertook a
      retrospective study based on the patients' records in order to elucidate the
      course of the illness from the time of diagnosis until the end of treatment. The
      median age of the patients was 35 years (range 1.5-75 years). The follow-up
      period was one month-9.5 years. Preoperatively most patients had symptoms or
      clinical signs of compression of the optic pathways. Eighteen patients were
      operated by the transcranial route and six patients by the transsphenoidal route.
      Radical excision was achieved in 10 cases. Nine patients had recurrence of tumor.
      Postoperative endocrine disturbances were diagnosed in 19 cases. By the end of
      the follow-up eight patients were dead, of whom seven had had relapse of tumor.
      We recommend radical excision at the primary operation whenever possible, but the
      issue is controversial.

PMID- 7645113
TI  - [Contamination of a water system with sewage].
AB  - The purpose of the study was to examine the extent of illness caused by
      contamination of a waterworks with waste water due to overflow. Structured
      questionnaires were mailed to all 703 households (the main study group) and four
      day-care centers supplied by the waterworks as well as a group of 200 randomly
      chosen households in neighbouring communities with a different water supply.
      Fourteen hundred and fifty-five persons (88% of respondents in the main study
      group) reported that they had had symptoms of gastroenteritis, particularly
      diarrhoea (83%) and vomiting (55%). In the control group, 10% of respondents had
      had symptoms of gastroenteritis. Onset of diarrhoea correlated well with
      precipitation (Spearman's correlation coefficient: 0.75; p = 0.0002). No
      pathogens were found. It is important to be aware of the possibility of water
      contamination when an increased number of cases of gastroenteritis are observed
      in a local area and to report even a suspicion of waterborne diseases to the
      county public health office.

PMID- 7645114
TI  - [Pulmonary arteriovenous malformations determined by color Doppler
      ultrasonography].
AB  - Pulmonary arteriovenous malformations are rare conditions, and are often
      misinterpreted on chest radiographs. We present a case in which peripherally
      localised pulmonary arteriovenous malformations were diagnosed by use of colour
      Doppler ultrasonography.

PMID- 7645115
TI  - [Abuse--of hospital services too].
AB  - A 75 year-old man with a well known opioid abuse is described. Within the last 10
      years the patient had 161 acute admissions to hospital--in total 942 in-hospital
      days. The diagnoses were either angina pectoris, low back pain or migraine. With
      time, the patient had become very skilled in mimicking these three diseases,
      knowing all subjective and objective signs even better than most of his doctors.
      In connection with all admissions he received the opioids he wanted.
      Nevertheless, he was astonished that it was so easy to fool the doctors. It is
      recommended that the patients' own doctor should be the coordinator and the only
      person responsible for prescription of opioids to these patients. In case of
      admissions to hospital, this should only be possible to a few selected
      departments who know the patient.

PMID- 7645116
TI  - [Allergy to natural rubber. A current problem].
AB  - Three cases of immediate type hypersensitivity to natural rubber latex are
      described. Unexpected, severe reactions were seen in two patients. One patient
      had used rubber gloves regularly and experienced moderate local symptoms. She had
      to change job because of generalised urticaria and asthma due to airborne latex
      allergens in the workplace. The diagnosis of latex allergy may not always be
      obvious, and negative or weak IgE-RAST can be seen in patients who have
      experienced severe allergic reactions after latex exposure. Cross reactions to
      banana, avocado, kiwi and possibly other fruits and plants may be seen. Medical
      staff using latex gloves should be aware of the risk of severe adverse reactions
      in their patients due to latex allergy. Gloves made from vinyl or other synthetic
      materials (i.e. Elastyren or Tactylon) can be used in these cases.

PMID- 7645117
TI  - [Acetylsalicylic acid intolerance].

PMID- 7645118
TI  - [Use of calcium channel blockers].

PMID- 7645119
TI  - [Anesthesia in obese patients--pharmacokinetic aspects].

PMID- 7645120
TI  - Ultrasonic three-dimensional reconstruction of the heart.
AB  - The recent advances in ultrasound equipment, digital image acquisition, and
      display techniques made three-dimensional (3D) echocardiography a clinically
      feasible and exciting technique which allows objective analysis of structure and
      pathological conditions of complex geometry. In this report, different image
      acquisition techniques are described and compared. In our experience, with
      rotational scanning the acquisition of cross-sections for 3D reconstruction
      becomes an integral part of a routine diagnostic study, both with a multiplane
      transesophageal imaging transducer, and in precordial echocardiography. After
      digital reformatting and image processing, a volumetric data set is obtained,
      which allows the display of synthetic cross-sections in various orientations
      independent from the point of origin of the sector scan [anyplane two-dimensional
      (2D) imaging]. This also offers the possibility of volume quantification, without
      the assumption of theoretical geometrical model of the cavity. Finally, dynamic
      volume rendered display can be applied for the objective display of the anatomy
      and the complex relationship among the different structures.

PMID- 7645121
TI  - Preliminary investigation of ultrasound scattering analysis to identify women at
      risk for later invasive cancer. I: Motivation and experimental technique for
      characterization of isolated breast tissue lobules.
AB  - A new experimental technique is described that allows the characterization of the
      angle-dependent ultrasonic scattering properties of isolated breast tissue
      lobules. A review of breast tissue micro-architecture is presented as background
      material. Measured estimates of the scatter angle-dependent differential scatter
      cross-sections (DSC) from 31 excised lobules (14 cancer in situ, 17 noncancer)
      were examined, and dominant trends described by statistical factors. Three
      factors were extracted, using principal component factor analysis, which
      collectively accounted for over 70% of the scatter angle-dependent variation
      exhibited by the measured data.

PMID- 7645122
TI  - Preliminary investigation of ultrasound scattering analysis to identify women at
      risk for later invasive cancer. II: Extraction of dominant scattering angle
      dependent trends from excised breast tissue.
AB  - Normalized estimates of the scattering angle-dependent differential scattering
      cross-section (DSC) at 1.0 MHz were measured from 278 samples of excised breast
      tissue taken from 66 women. A comparison of results for samples that contained
      tissue structures previously associated with an increased probability of
      developing breast cancer to those that did not contain high-risk structures
      showed that the average magnitude of DSC estimates was insufficient to identify
      samples with high-risk lesions. Principal component factor analysis (PCFA) was
      applied to extract scattering angle-dependent trends common to the entire data
      base. The normalized estimates of the measured DSCs (NDSC) from tissue samples
      are compared to estimates previously obtained from isolated breast tissue lobules
      as well as with results from the PCFA. Results are presented that indicate that
      the dominant angle-dependent trends in the NDSC results are independent of the
      age of the patient and are similar to trends extracted from isolated breast
      tissue lobules. The breast tissue structure common to all of these specimens is
      the terminal duct.

PMID- 7645123
TI  - Reproducibility of Doppler measurements of blood flow velocity in the uterine and
      ovarian arteries in premenopausal women.
AB  - Intra- and interobserver reproducibility of Doppler measurements of the
      pulsatility index (PI) and time-averaged maximum velocity (TAMXV) in the uterine
      and ovarian arteries were evaluated in examinations of healthy premenopausal
      women. Each woman underwent reproducibility measurements once in the late
      follicular phase and once in the midluteal phase. Intraobserver repeatability was
      assessed in examinations of 12 women, three replicate Doppler measurements being
      made by one observer in the same vessel. Interobserver agreement was assessed by
      comparing the results of Doppler measurements made by two investigators in 11
      women. The intraclass correlation coefficient (Intra-CC) was 0.78 for the TAMXV
      in the dominant uterine artery in the follicular phase and 0.82 for the PI in the
      wall of the dominant follicle. For all other measurements the Intra-CC was <
      0.75, indicating poor reproducibility. The interclass correlation coefficient
      (Inter-CC) was > 0.75 (0.79 to 0.88) for the PI and TAMXV in the dominant uterine
      artery in the follicular phase and for the PI of both uterine arteries in the
      luteal phase. For all other measurements the Inter-CC was < 0.75.

PMID- 7645124
TI  - Vascular resistance quantification in high flow resistance areas using the
      Doppler method.
AB  - The objective of the present study is to define and validate on an animal model
      (ewe) a new Doppler parameter for the assessment and monitoring of the vascular
      resistances in high resistance to flow areas (lower limbs, placenta with vascular
      disease). The high resistance index (HRI) was derived from the transmission line
      theory and defined as: HRI = D/S with S the amplitude of the systolic peak and D
      that of the diastolic reverse flow. Validation of the HRI was performed on adult
      ewes. Distal lower limb vascular resistances were evaluated from the Doppler
      femoral waveform (HRI) and compared with the classic vascular resistances (Rv),
      calculated from pressure and flow (mmHg/mL/min). The femoral flow variations were
      measured by duplex (echo-Doppler) method and the mean pressure through an
      arterial catheter inserted into the abdominal aorta. Two tests were used in this
      study: (1) A calibrated venous compression of the lower limbs extremity: The
      femoral flow dropped by 29%, the pressure and heart rate did not change, the HRI
      increased by 37% (p < 0.01), and the vascular resistance (Rv) by 46% (p < 0.01).
      (2) The intravenous injection of 1 mg adrenaline: The arterial pressure increased
      by 70% (p < 0.001), the heart rate and femoral flow dropped by 50% (p < 0.001),
      and 35% (p < 0.001), the HRI increased by 70% (p < 0.01) and the vascular
      resistances (Rv) by 140% (p < 0.01). During the two tests, the HRI changed in
      proportion with the "classic" vascular resistances.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7645125
TI  - The subtleties of ultrasound images of an ensemble of cells: simulation from
      regular and more random distributions of scatterers.
AB  - Significant differences in the backscatter amplitudes which are correlated with
      different tissue morphology have been observed in ultrasound images of tissue.
      While many factors could be linked to subtle changes in the images, the purpose
      of this paper is to explore the possibility that backscatter signals are linked
      to the organization of the spatial distribution of individual cells that produce
      an ensemble of scattering sources. Simple one- and two-dimensional simulations of
      backscatter signals produced by weak scatters separated by << lambda to < lambda
      in regular, random, and pseudo-random distributions in a "sample" are performed.
      Both regular and pseudo-random distributions produce large boundary signals, and
      in the central regions of the sample, the square root of the backscatter power is
      directly related to the amount of randomization, R, over a large range. Large
      changes in backscattering intensities are predicted for the same density of
      scatterers with differing R in different regions of the same sample. Thus, the
      subtle differences in the scattering distribution should show significant changes
      in the backscatter images.

PMID- 7645126
TI  - A study of the relationship between mechanical and ultrasonic properties of
      dystrophic and normal skeletal muscle.
AB  - A study has been made of the application of radio frequency (RF) ultrasound to
      the detection of muscular dystrophy by monitoring passively stretched skeletal
      muscle. The tests included detection of integrated backscatter changes in
      response to both static loading, in which muscle samples were stretched and
      allowed to relax, and stress relaxation. In both static and step strain loading
      conditions, the dystrophic muscle was found to exhibit little change in
      backscatter power while normal muscle responded to loading with significant
      changes in integrated backscatter. The backscatter response is compared with
      mechanical properties of the tissue (time constants and stress-strain constants).
      Both mechanical and ultrasonic time constants of relaxation are not significantly
      different between normal and dystrophic tissue, but stress-strain constants do
      differ. The difference in response of dystrophic and normal tissue appears to be
      due to a repression of motion of the constituent anatomy of dystrophic muscle
      which is responsible for the change of echogenicity with passive stretch.

PMID- 7645128
TI  - Electronic beam steering of shock waves.
AB  - Shock-wave generators are now currently used for the treatment of renal stones.
      In all these generators the focal zone is determined by their geometrical
      parameters. We propose, for the first time, a piezocomposite shock-wave generator
      with electronic focusing. The system is composed of a two-dimensional array and
      its electronic hardware. The array is composed of 121 independent piezocomposite
      transducers arranged in a spherical shell 20 cm in diameter and focused at 190
      mm. The electronic hardware includes 121 x 6 kV-impulse generators. The
      interdelay of each channel can be adjusted between 10 ns to 100 microseconds by
      steps of 10 ns. The results show: the use of composite material is possible for
      the generation of high amplitude pressure waves; the pressure-voltage
      relationship is linear up to a pressure of about 28 x 10(5) Pa at the transducer
      front face; the material can be used for a long period of time; i.e., after one
      million shocks, no decrease in sensitivity, no alteration in its electrical
      behaviour and no time wave form distortion were observed. Electronic focusing is
      efficient in an ellipsoidal region of about 4 cm in diameter and 6 cm in length.
      The pressure in the focal zone is about 600 x 10(5) Pa.

PMID- 7645127
TI  - Modification of intensity distributions from large aperture ultrasound sources.
AB  - The Fresnel-Kirchhoff diffraction theory has been used to model the acoustic
      fields produced by a variety of apodizations of large aperture, axially symmetric
      ultrasound sources. The forms of resulting intensity maxima and their resulting
      suitability for surgical lesioning of tissues are compared, through a "lesioning
      capability" and a "focal efficiency." Although only modest changes in intensity
      distribution are possible, some may have applications in making arrays of lesions
      for control of focal cancer and other pathologies.

PMID- 7645130
TI  - Macroscopic ESWL-induced cavitation: in vitro studies.
AB  - The rarefaction shock wave results in a liquid failure at the target/fluid
      interface. In the wake of the reflected ESWL-induced shock wave, a macroscopic
      cavity is generated in filtered water. The cavity implosion induces a large shock
      wave, divulging the bubble existence and lifetime. The existence of this shock
      wave is revealed by the diffraction of a He-Ne laser beam. The induced cavitation
      bubbles are registered by a camera, illuminated by an externally triggered
      stroboscope (exposure time 10 microseconds). The radius of the large cavity
      bubble, generated at the stone surface, is time dependent as theoretically
      predicted.

PMID- 7645129
TI  - In situ human obstetrical ultrasound exposimetry: estimates of derating factors
      for each of three different tissue models.
AB  - A specialized in vivo exposimetry system was developed to acquire transabdominal
      in situ ultrasound exposure quantities in obstetric patients. Under surgical
      conditions, the sterilized 7-element calibrated linear array hydrophone was
      introduced into the uterus under direct ultrasound guidance and placed in direct
      contact with the products of conception, usually in the saggital midplane of the
      uterine cavity. Twenty-five patients with empty bladders and 10 patients with
      full bladders were studied at gestational ages between 7 and 20 weeks. In the
      empty bladder condition, the sound beam traversed the anterior abdominal wall,
      uterus, amniotic fluid and fetal parts and in the full bladder condition, the
      sound beam also traversed the fluid-filled bladder. Each study was conducted with
      a 3 MHz, mechanical sector transducer in combination with an ATL Ultramark 4
      diagnostic ultrasound imaging system. Calibration data were recorded after
      completion of each in vivo patient study. The acquired exposimetry data from the
      35 obstetric patients were used to evaluate the appropriateness of three tissue
      attenuation models, viz., fixed path, homogeneous and overlying. All three tissue
      models yield a mean attenuation coefficient value of about a factor of 3 to 4
      greater than their respective minimum values. In the case of the overlying and
      homogeneous tissue models, there was a statistically significant correlation
      between their calculated attenuation coefficients and total distance for the
      combined data set whereas there was no such dependency for the calculated fixed
      path tissue model. In summary, any one of the three tissue models may be used to
      estimate in utero acoustic quantities during the first and second trimesters of
      human pregnancy based on this study.

PMID- 7645131
TI  - Effects of piezoelectric lithotripsy on human DNA.
AB  - Genomic DNA was extracted from excised gallbladder mucosa, obtained shortly after
      a single treatment piezoelectric lithotripsy. Control samples were obtained from
      age and sex-matched patients who had received no lithotripsy. No DNA
      fragmentation was demonstrable on agarose gel electrophoresis. Suspensions of
      cultured lymphoblasts were subjected to different shock wave doses and the
      percentage of cells surviving the treatment was assessed immediately and the rate
      of cell death monitored over the following 7 h. The proportion of cells surviving
      the treatment decreased with increasing shock wave doses, but subsequent rate of
      cell death was no different from controls. DNA, extracted from the intact
      surviving cells, again showed no evidence of fragmentation on electrophoresis,
      but the DNA extracted from the supernatant showed extensive fragmentation.

PMID- 7645132
TI  - The cavitation threshold of human tissue exposed to 0.2-MHz pulsed ultrasound:
      preliminary measurements based on a study of clinical lithotripsy.
AB  - Evidence of acoustic cavitation was identified in the form of transient echoes in
      ultrasound B-scan images of patients receiving extracorporeal shock-wave
      lithotripsy treatment on a Storz Modulith SL20. This lithotripter generates 10
      microseconds duration pulses with a centre frequency of 0.2 MHz at a pulse
      repetition frequency of 1 Hz. The visual appearance of B-scan images was examined
      in a total of 30 patients and a quantitative analysis of echogenicity changes was
      carried out in six cases involving lithotripsy treatment of stones in the renal
      pelvis. In these patients new echoes were identified in images unaffected by
      movement artefacts and were found to occur in perinephric fat and adjacent muscle
      and kidney tissue at positions close to the axis of the shock-wave field between
      1 and 2 cm in advance of the indicated beam focus of the lithotripter. The
      echogenicity within each region increased significantly above the background
      level when the output of the lithotripter was increased above a threshold value.
      The acoustic pressures corresponding to this threshold were measured in water
      using a calibrated PVDF membrane hydrophone. After correction for attenuation in
      tissue the cavitation thresholds, in terms of the temporal peak negative
      pressure, are found to lie between 1.5 MPa and 3.5 MPa in all six cases.
      Interpretation of the measured values in terms of the likely threshold at the
      higher frequencies used in diagnostic ultrasound is considered using a
      theoretical model.

PMID- 7645133
TI  - Ultrasound accelerates transport of recombinant tissue plasminogen activator into
      clots.
AB  - Fibrinolysis is accelerated in vitro in an ultrasound field, and externally
      applied high frequency ultrasound also accelerates thrombolysis in animal models.
      Although the mechanism of this effect is not known, ultrasound does not cause
      mechanical disruption of clots but rather accelerates enzymatic fibrinolysis. To
      determine if accelerated fibrinolysis could be related to increased transport of
      enzyme into clot, we have examined the effect of insonification on the
      distribution of plasminogen activator between clot and surrounding fluid in
      vitro. Plasma clots were overlayed with plasma containing 125I-radiolabeled,
      active-site-blocked recombinant tissue plasminogen activator (rt-PA) and
      incubated in the presence of 1-MHz ultrasound at 4 W/cm2 or in the absence of
      ultrasound. The rate of uptake of rt-PA was significantly faster in the presence
      of ultrasound, reaching 15.5 +/- 1.4% at 4 h compared to 8.2 +/- 1.0% in the
      absence of ultrasound (p < 0.0001). Similarly, ultrasound increased transport of
      enzyme from the clot into the surrounding fluid. To determine the effect of
      ultrasound on the spatial distribution of enzyme, plasma clots were overlayed
      with plasma containing radiolabeled rt-PA and incubated in the presence or
      absence of ultrasound. The clots were then snap-frozen, and the radioactivity in
      serial cryotome sections was determined. Exposure to ultrasound altered the rt-PA
      distribution, resulting in significantly deeper penetration of rt-PA into the
      clots. We conclude that exposure to ultrasound increases uptake of rt-PA into
      clots and also results in deeper penetration. These effects of ultrasound on
      enzyme transport may contribute to the accelerated fibrinolysis observed in an
      ultrasound field.

PMID- 7645134
TI  - Prenatal application of diagnostic ultrasound in mice.

PMID- 7645135
TI  - Comparison of ultrasound irradiation of pregnant mice with other bioeffects data.

PMID- 7645136
TI  - Treatment of advanced renal cell carcinoma using regional arterial administration
      of lymphokine-activated killer cells in combination with low doses of rIL-2.
AB  - We investigated the usefullness and problems of arterial administration of
      lymphokine activated killer (LAK) cells in combination with systemic IL-2 in the
      treatment of metastatic renal cell carcinoma (RCC). Ten nephrectomized patients
      with extrapulmonary and/or nonresectable metastases were treated with arterial
      infusions of LAK cells and systemic rIL-2 (5 x 10(5) IU twice a day) for 1-12
      weeks. Leukapheresis was carried out once or twice a week, and two LAK cell
      populations generated from two gravity subtypes of peripheral blood lymphocytes
      were administered separately. Five of 15 metastases treated showed appreciable
      regression of metastatic sites including bone, muscle and lymph nodes. Two of 15
      showed a minor response. Local pain due to metastasis was relieved or disappeared
      in 6 patients. There was no correlation between the response of the patients and
      the number of LAK cells used. The 24- and 56-month survival rate was 50 and 25%,
      respectively. No serious side effects were experienced during treatment. We
      conclude that regional arterial administration of LAK cells in combination with a
      low dose of IL-2 is worthwhile as an alternative treatment modality to
      conventional therapy for a selected group of patients with advanced RCC.

PMID- 7645137
TI  - High frequency of human papillomavirus detection in urinary bladder cancer.
AB  - We investigated the presence of human papillomaviruses (HPVs) types 16 and 18 DNA
      in formalin-fixed, paraffin-embedded tissues from the urinary bladder (46
      transitional carcinomas and 10 non-neoplastic normal urinary samples) to find a
      possible role for HPV types in urinary tract cancerogenesis. The analysis was
      performed using polymerase chain reaction followed by filter hybridization with
      oligonucleotide-specific probes. The HPV16 and/or HPV18 genomes were detected in
      23 of 46 (50%) bladder carcinomas and in none of 10 (0%) non-neoplastic urinary
      samples. These results suggest that HPV16 and 18 may carry a risk for the
      development of malignancy in the urinary tract as it occurs in the anogenital
      regions.

PMID- 7645138
TI  - Prognostic factors in disseminated prostatic cancer, with special emphasis on
      extent of disease.
AB  - Current clinical trials in disseminated prostatic cancer mostly use M0 or M1 to
      identify two prognostically different groups of patients. Soloway et al. [Cancer
      1988;61:195-202] have shown a significant difference in survival depending on the
      extent of disease (EOD) on bone scan in M1 disease. Seventy-three prostatic
      cancer patients with bone-scan-proven metastases (T0-4 Nx M1 G1-3) from the Aust
      Agder County in Norway with observation time 2-9 years were followed. The impact
      of T stage, grade, serum acid phosphatase status and EOD on survival was
      analyzed. EOD was assessed according to Soloway et al. No statistically
      significant difference could be demonstrated according to T stage or histological
      grade. A statistically significant difference in survival could be demonstrated
      both for normal versus elevated serum acid phosphatase and for EOD. EOD I/II had
      a better prognosis than EOD III/IV. Stratification of patients in EOD categories
      seems relevant, but the relative importance of the different EOD categories is
      not yet established.

PMID- 7645139
TI  - Clinical and pathological features of highly malignant prostatic carcinomas with
      metastases to the penis.
AB  - Since 1885, 73 penile metastases of a primary carcinoma of the prostate have been
      reported. There is no standardized therapy as various therapeutic methods have
      produced variable results. The authors present their experiences with 2 recent
      cases. In some cases, total penectomy can relieve untolerable pain.
      Immunohistochemistry and flow cytometry for various prognostic factors showed a
      high malignant potential of carcinomas of the prostate metastasizing to the
      penis. Screening for various prognostic factors could favor an initial, more
      radical surgical approach in some cases, thus avoiding later tumor progression.

PMID- 7645140
TI  - Transrectal ultrasonography of the prostate and seminal vesicles with
      hemospermia.
AB  - Transrectal ultrasonography was performed in 46 patients with hemospermia.
      Abnormal findings in the prostate and seminal vesicles, including prostatic
      stones, benign prostatic hyperplasia, prostatitis, and dilatation and calculi of
      the seminal vesicles, were observed in 34 patients (73.9%). However, no malignant
      lesions were found in the prostate or seminal vesicles. Transrectal
      ultrasonography was a useful and noninvasive procedure to investigate the causes
      of hemospermia. Furthermore, transrectal ultrasonography could demonstrate latent
      diseases and exclude malignancy of the prostate and seminal vesicle in patients
      with hemospermia.

PMID- 7645141
TI  - Vasovasostomy results in 66 patients related to obstructive intervals and serum
      agglutinin titres.
AB  - In this series we present the results of a retrospective analysis of 66
      vasovasostomy procedures performed between 1983 and 1991. Obstructive intervals
      and serum antisperm antibodies were correlated with pregnancy and patency rates.
      With obstructive intervals of less than 5 years a patency rate of 100% (31/31)
      was obtained. Even more than 10 years after reversal, pregnancy occurred in 25%
      (2/8) of the patients. Preoperative serum antisperm antibodies were correlated
      with pregnancy rates. Patients with a high agglutinin titre of 1/64 obtained a
      pregnancy rate of 23% (3/13). Those men who had no circulating antisperm
      antibodies in their blood had a significantly better chance in obtaining
      pregnancy (pregnancy rate 80%). In this study we accounted for an overall
      pregnancy rate of 51.5% (34/66) versus an overall patency rate of 84.8% (56/66).
      Neither long obstructive intervals nor high antisperm antibody titres should
      dissuade a surgeon from performing a vasovasostomy procedure.

PMID- 7645142
TI  - Penile block via subpubic space for children who underwent superficial operation
      of the penis.
AB  - Penile nerve block via the subpubic space was performed to relief the
      postoperative pain of children who underwent superficial surgery of the penis.
      Thirty-one male children were subdivided into two groups. After dorsal split
      procedure had been carried out under general anesthesia, 16 patients underwent
      subpubic penile nerve block (group 1), while 15 patients had no additional
      anesthetic procedure (group 2). Time to the first postoperative pain in group 1
      was statistically longer than that in group 2 (p < 0.05). Most patients in group
      1 did not require postoperative analgesics during the first 24 h after surgery.
      This technique appeared to be effective in relieving the postoperative pain of
      children who underwent superficial operation of the penis.

PMID- 7645143
TI  - Evaluation of urodynamic parameters following Burch colposuspension.
AB  - Burch colposuspension is a very popular operation for the correction of genuine
      stress incontinence, due to its very good long-term results. The effect of the
      operation on the urodynamic parameters at the level of the bladder neck evaluated
      in this study, and correlated with clinical outcome. A total of 29 female
      patients with urinary stress incontinence who underwent a Burch colposuspension
      were clinically and urodynamically studied pre- and postoperatively. The
      urodynamic parameters chosen pre- and post-operatively were: maximum flow rate,
      residual urine, first sensation, bladder capacity, maximum detrusor pressure,
      detrusor pressure at maximum flow, functional urethral length and maximum closure
      pressure. Complete cure was obtained in 76% of the patients and improvement in
      14%, the overall success rate being 90% for a mean follow-up of 18.4 months
      (range 8-27). Comparison of the pre- and postoperative urodynamic data revealed
      that the maximum urine flow rate, functional urethral length, maximum urethral
      closure pressure and residual urine were changed significantly after the
      operation. There were no statistical differences in the other parameters. All the
      urodynamic results that improved, however, only arrived at the lower limits of
      the values accepted as standard for normal individuals. This fact, however, did
      not prevent a good clinical result.

PMID- 7645144
TI  - Giant segmental hydronephrosis of a horseshoe kidney: diagnostic dilemma.
AB  - We report a case of giant segmental hydronephrosis of the right moiety of a
      horseshoe kidney. The diagnosis was not established until exploration, despite
      thorough evaluation by all the available imaging techniques.

PMID- 7645146
TI  - Primary leiomyosarcoma of the ureter.
AB  - Malignant tumors of the ureteral smooth muscle are rare and the prognosis is not
      clear. This is a report of a patient with primary leiomyosarcoma of the ureter
      surviving 9 years and 9 months postoperatively without any evidence of
      recurrence. Malignancy of the ureter was suspected on the basis of angiography
      and radical nephro-ureterectomy was performed without positive cytology results.

PMID- 7645147
TI  - Parameatal urethral cyst: case reports and review of the literature.
AB  - Four cases of parameatal urethral cysts are presented. Etiology and treatment are
      discussed.

PMID- 7645145
TI  - Simple renal cortical cysts in children: two uncommon case reports.
AB  - Two cases of simple renal cortical cysts in children are presented. In the first
      case, the cyst was detected antenatally and was followed for about 3 weeks
      postnatally till it was resected. The second case is an 11-year-old boy with a
      giant simple renal cyst exceeding 15 cm in diameter. Both cases are uncommon. The
      diagnostic problems regarding large intra-abdominal cystic masses are emphasized.

PMID- 7645148
TI  - A case of posttherapeutic sclerotic change of bone metastasis from renal cell
      carcinoma which proved histopathologically to be complete response.
AB  - A 60-year-old man with renal cell carcinoma and metastases to the right 7th rib
      and L2 vertebra (T2N0M1, OSS) was treated with interferon-alpha and the uracil
      and tegafur combination following nephrectomy. One and a half years later on bone
      scintigraphy, the abnormal accumulation had disappeared at the L2 vertebra and
      weakened in its intensity at the right 7th rib. Plain X-ray revealed that the
      metastatic lesion at the right 7th rib had decreased in size and had been
      replaced by calcification. The right 7th rib was removed surgically and step
      sectioned pathological specimens revealed necrosis with no viable cancer cells.

PMID- 7645149
TI  - Orchitis following mumps vaccination in an adult.
AB  - An acute epididymo-orchitis, followed by a viral arthritis of the left hand,
      occurred as complications of a mumps vaccination. In the last 17 years 4 certain
      cases of orchitis following vaccination have been published in Germany. We
      describe an additional case and discuss the possible consequences.

PMID- 7645150
TI  - Epidemiology and psychosocial aspects of incontinence.
AB  - UI in women is a highly prevalent condition. It affects women of all ages,
      domicile, or health status. UI is highly correlated with several medical
      conditions, including physical mobility problems, neurologic conditions, bowel
      problems, respiratory problems, and lower urinary tract problems. It also affects
      negatively the social and psychologic well-being of the affected individual. Many
      of the urodynamic parameters commonly tested showed no significant difference
      between continent and incontinent subjects. The few parameters that showed
      significant difference between the two groups have values that are overlapping.
      Lastly, the incidence and remission rates of urinary incontinence in elderly
      women are available and are significant.

PMID- 7645151
TI  - Functional female pelvic anatomy.
AB  - This article reviews important aspects of female pelvic anatomy with particular
      emphasis on the structures important for pelvic organ support and urinary
      control. The pelvis and supporting structures, the pelvic floor, and the
      relationships of the pelvic organs are described and illustrated by MR imaging.

PMID- 7645152
TI  - Pathology and pathophysiology of detrusor in incontinence.
AB  - Incontinence is a common urologic problem, especially in the elderly.
      Ultrastructural study of the detrusor is crucial for the understanding of its
      normal and abnormal functional behavior. Prospective, correlative,
      ultrastructural studies in the elderly revealed distinctive patterns of the
      overactive (unstable) detrusor, whether occurring alone or together with impaired
      detrusor contractility or bladder outlet obstruction. These patterns provide
      better insight into pathophysiology of the unstable bladder, and a great
      potential in diagnosis of detrusor dysfunction in general.

PMID- 7645153
TI  - Preliminary assessment of the incontinent woman.
AB  - Assessment of urinary incontinence begins with a thorough history and physical
      examination. This article reviews the collection of subjective, semi-objective,
      and objective data that allows for comprehensive evaluation of the incontinent
      female patient. These results will help direct further evaluation and develop an
      efficient and effective treatment plan.

PMID- 7645154
TI  - Urinary incontinence in girls. Evaluation, treatment, and its place in the
      standard model of voiding dysfunctions in children.
AB  - Urinary incontinence is the principle voiding dysfunction of childhood. This can
      be viewed as one among many dysfunctions in our standard model of voiding
      dysfunction. A careful elimination history is essential to manage any voiding
      dysfunction.

PMID- 7645155
TI  - Radiography, sonography, and magnetic resonance imaging for stress incontinence.
      Contributions, uses, and limitations.
AB  - Imaging has increased our ability to understand stress incontinence and prolapse
      and has advanced our existing concepts of pathophysiology. Once these conceptual
      contributions have been made, imaging modalities may fade from current use, but
      the lessons learned will remain. It is the relationship of clinical imaging to
      conceptual development that is important. Conventional radiographic studies are
      well understood and can be obtained in most facilities. Sonographic units are
      currently available in many urologic and gynecologic clinics and offices and can
      be adapted for stress incontinence studies. The benefits of real-time studies and
      soft-tissue detail at the urethrovesical junction and office-based convenience
      make this an attractive new technique. The global pelvic approach offered by MR
      imaging offers spectacular imaging possibilities, which can help in complex cases
      and in future concepts in the field. MR imaging is rapidly evolving and may
      continue to offer new insights as technology permits. In accordance with
      Hodgkinson's earlier observations, imaging should not be routinely required in
      all patients undergoing evaluation for stress incontinence, but should certainly
      be considered in failed operations, complex prolapse, and when clinical diagnosis
      is in doubt. It is always better to use an imaging technique, no matter how
      expensive, than to end up with a bad surgical result.

PMID- 7645156
TI  - Urodynamic evaluation of stress incontinence.
AB  - A careful history points the urodynamic examination in the right direction and
      enables the examiner to ask the correct questions. The individual who does the
      test is the only reliable interpreter of the results of that study. No urodynamic
      technique is as sensitive or specific as a blood glucose, or even an
      electrocardiogram. A history of urgency and urge incontinence suggests
      uninhibited contractility and is a better index of that condition than a
      cystometrogram. Leakage occurring shortly after a previous operative procedure
      for stress incontinence suggests type III stress incontinence. A past history of
      radiation, prior pelvic surgery, neurologic disease, herniated disc conditions,
      or prior chemotherapy all require a simple cystometrogram to rule out abnormal
      bladder compliance. Following a simple history and urodynamic evaluation, a
      physical examination should be performed, searching for urethra hypermobility and
      genital prolapse. Abdominal leak-point pressure testing is useful to assign broad
      categories of incontinence. Relatively high leak-point pressures with
      hypermobility suggest suspension operations will be effective. Low leak-point
      pressures with hypermobility often require a sling, and very low leak-point
      pressures with no hypermobility indicate a suitable candidate for a trial of
      injection therapy.

PMID- 7645157
TI  - Pharmacology of incontinence.
AB  - Any type of filling or storage failure and urethral incontinence results from the
      following abnormalities: accommodation of increasing volumes of urine at a low
      intravesical pressure and with appropriate sensation, a bladder outlet that is
      closed at rest and remains so during increase in intra-abdominal pressure, and
      absence of involuntary bladder contraction. This article discusses the
      pharmacologic therapy that is effective in the management of many types of
      voiding dysfunction.

PMID- 7645158
TI  - Neurogenic vesical dysfunction.
AB  - Women with neurogenic vesical dysfunction are prone to the development of
      urologic complications. These patients require diagnostic evaluation including
      the use of urodynamic study, imaging, and often endoscopy. These studies
      ultimately determine whether medical management or surgical intervention will
      minimize the long term risk of urologic complications. Proper definitive
      treatment of this patient group effectively enhances quality of life and patient
      satisfaction.

PMID- 7645159
TI  - Detrusor instability.
AB  - Detrusor instability is a common cause of urgency and urge incontinence in
      neurologically normal patients. It is defined as an involuntary phasic detrusor
      contraction of any pressure associated with symptoms of urge or leakage while the
      patient is attempting to inhibit micturition. The etiology is unknown but it has
      been associated with congenital causes, aging, stress incontinence, and bladder
      outlet obstruction. Diagnosis relies on a urologic history and physical
      examination, a voiding diary, and a urodynamic evaluation. Treatment is primarily
      pharmacologic and behavioral, with surgical options being reserved for selected
      patients.

PMID- 7645160
TI  - Nonsurgical therapy for stress incontinence.
AB  - This article discusses the therapies that have been developed for the treatment
      of stress incontinence due to female pelvic-floor dysfunction. A combination of
      pelvic muscle exercises, biofeedback, behavioral modification, and electrical
      stimulation are all treatment options that do not involve surgery. When
      physiotherapy proves successful, and surgery is avoided, it is necessary for the
      patient to be put on a maintenance program to avoid relapse. The authors also
      discuss the link between urinary stress incontinence and women involved in
      sports.

PMID- 7645162
TI  - Vaginal reconstructive surgery for female incontinence and anterior vaginal-wall
      prolapse.
AB  - The surgical procedure of choice to correct stress urinary incontinence using a
      vaginal approach depends not only on the anatomic origin of the incontinence
      (hypermobility or intrinsic sphincter dysfunction) but also on the degree of
      coexistent anterior vaginal wall prolapse. The grade of coexistent cystocele and
      the finding of a central or lateral defect are important observations that help
      the surgeon plan the optimum surgical approach. Grade 4 cystocele with central
      and lateral defects represents the most severe form of anterior vaginal wall
      prolapse. In this case, the surgical goals are to correct both central and
      lateral defects, as well as hypermobility related to the mid-urethra and bladder
      neck.

PMID- 7645163
TI  - Surgical treatment of intrinsic urethral dysfunction. Slings.
AB  - Slings are a durable and effective treatment for intrinsic sphincter deficiency,
      regardless of its etiology. The history of slings throughout the 20th century,
      and the current surgical technique, is described in this article. A comparison of
      slings with alternative treatments of intrinsic sphincter deficiency, such as
      artificial sphincters and collagen is presented. Slings play a significant role
      in the treatment of stress incontinence.

PMID- 7645161
TI  - Hormonal influence on the urinary tract.
AB  - This article describes the hormonal changes in the female and the effect of these
      changes on the urinary tract. Current concepts in hormone replacement therapy as
      it relates to incontinent, estrogen-deficient women are discussed, along with the
      relationship between collagen and estrogen. Finally, the authors assess the
      published research on the effect of estrogen on incontinence.

PMID- 7645164
TI  - Surgical treatment of intrinsic urethral dysfunction: injectables (fat).
AB  - Injection of autologous fat has been used for many years to correct cosmetic
      surgical defects. More recently, autologous fat injection has been applied to the
      treatment of urinary incontinence. The background and technique of periurethral
      fat injection are described in this article. The technique is safe, and
      preliminary results are encouraging in women with intrinsic sphincter deficiency.
      Long term follow-up and comparative trials will determine the ultimate utility of
      periurethral fat injection for the treatment of women with intrinsic sphincter
      deficiency.

PMID- 7645165
TI  - Periurethral injection of collagen in the treatment of intrinsic sphincteric
      deficiency in the female patient.
AB  - In properly selected patients, the periurethral injection of collagen is a safe
      and effective form of management for females with intrinsic sphincteric
      dysfunction. Performed under local anesthesia, this procedure allows for the
      treatment of patients who may not be suitable candidates for anesthesia and
      formal surgery. In female patients, excellent treatment results are obtained,
      which appear durable for greater than 2 years; these results are obtained usually
      within three treatment sessions. Periurethral collagen injection has been shown
      to elicit only a minimal inflammatory reaction and there have been no adverse
      immunogenic effects, foreign-body reaction, or migration of the injected
      material. Adverse events associated with the periurethral injection of collagen
      are rare. Collagen has proven to be a highly efficacious substance for use in
      periurethral injections for the treatment of intrinsic sphincteric dysfunction.

PMID- 7645166
TI  - Application of organ transplant techniques to urologic surgery.
AB  - This article presents a detailed description of surgical techniques that have
      been adapted from multi-organ procurement procedures and liver and pancreas
      transplantation that may be applied to urologic surgery, specifically difficult
      excision of urologic tumors in the upper abdomen and retroperitoneum. Techniques
      for exposure, mobilization of the liver, mobilization of the pancreas and spleen
      segment, isolation of the suprarenal intra-abdominal inferior vena cava, and the
      intra-abdominal approach of the intracardiac inferior vena cava through a
      pericardial window are described. The addition of the described techniques to the
      urologist's surgical armamentarium may be beneficial for providing increased
      access and exposure in difficult urologic cases.

PMID- 7645167
TI  - [Effects of low-intensity laser irradiation on several parameters of
      microcirculation in the bulbar conjunctiva of patients with scleroderma].
AB  - Computer-aided analytical system of TV images (CASTI) of the anterior segment of
      the eye revealed an appreciable increase of the level of aggregation gradient in
      arterioles and venules of the bulbar conjunctiva of 37 children suffering from
      various forms of scleroderma, as against 18 healthy children. Exposure to low
      energy laser of a close infrared band (approximately 890 nm) had a favorable
      impact on blood aggregation in patients with scleroderma. CASTI of the anterior
      segment of the eye proved to be an objective and highly informative method for
      the diagnosis and monitoring of the efficacy of various treatment modalities.

PMID- 7645168
TI  - [Neuro-ophthalmological symptoms of involvement of the infra-clinoid part of the
      internal carotid artery].
AB  - Arterial aneurysms of the infraclinoid part of the internal carotid artery
      manifest by Jefferson's I-II syndrome. Similar symptoms are observed in
      intracranial processes of other origin developing in the immediate vicinity from
      this portion of the internal carotid artery. The manifestation and type of these
      symptoms depend on the extension of the pathological process, its localization,
      and individual anatomic structure of oculomotor nerves.

PMID- 7645169
TI  - [Study of immune reactions to collagen in patients with myopia].
AB  - Fifty-five blood sera and twenty-three samples of lacrimal fluid of patients with
      medium and high myopia were tested for antibodies to the main structural protein
      of the sclera, collagen, by enzyme immunoassay. Serum autoantibodies to collagen
      were detected in 50-70% of patients with all forms of myopia (congenital, early
      acquired, and acquired at school age). Antibodies to collagen were not detected
      in the lacrimal fluid, which was regarded as an evidence of the predominance of
      systemic autoimmune reactions. Antibody titers were the highest in the blood sera
      of patients with uncomplicated and slowly progressing myopia. Rapidly progressing
      myopia complicated by mixed forms of peripheral vitreo-chorioretinal dystrophies,
      including ruptures of the retina, was characterized by a deficit of antibodies to
      collagen in the blood serum. This implies a possible protective role of
      antibodies to collagen detected in the blood of patients with myopia. These
      results are regarded as a proof in favor of the participation of autoimmune
      reactions to collagen in the pathogenesis of medium and high myopia.

PMID- 7645170
TI  - [Clinical-immunological and epidemiological studies in high complicated myopia].
AB  - A total of 100 patients with high complicated myopia were examined.
      Immunodeficiency syndrome and signs of autosensitization were revealed in this
      patient population. Analysis of morbidity and its relationship with some
      environmental factors and characteristics of the activity of public health system
      showed that the morbidity was related to increased radioactivity and to
      unsatisfactory status of water in a region, and that increase of the number of
      medical workers may help reduce the morbidity.

PMID- 7645171
TI  - [Diagnosis and classification of variants of color vision in the light of new
      methodological approaches].
AB  - The authors suggest that the parameters of color force of the receptors and the
      possible abnormal disposition of their maximal sensitivity by the spectrum be
      taken into consideration in the diagnosis of color perception. Assessment of
      color force was acknowledged to be more significant than of color abnormalities,
      both from a viewpoint of occupational selection, and from a clinical viewpoint.
      This is reflected in the suggested classification of color vision and in
      recommendations for use in practical ophthalmology of new threshold tables
      created by Yustova-Alexeyeva et al. These tables are based on the results of
      colorimetric investigations, and the results of their trials are reliable.

PMID- 7645172
TI  - [Color campimetry in the diagnosis of diseases of the retina and optic nerve].
AB  - Color campimetry was realized with the use of an IBM-compatible computer display
      with a program permitting the registration of brightness sensitivity thresholds
      and the time of sensorimotor reaction to visual stimuli offered on the display in
      each point of the visual field. Investigation of light and color sensitivity
      thresholds and of the time of sensorimotor reaction to stimuli of different
      spectral composition in normal subjects helped study the functional topography of
      the retina by the time of sensorimotor reaction and by the brightness sensitivity
      thresholds. The methods of equalization by the brightness of the stimulus and
      background by means of recording the time of sensorimotor reaction was tried in
      experiments with different background brightness and stimulus size and in
      ophthalmologic examinations of patients with color abnormalities, diseases of the
      retina and optic nerve, with glaucoma and albinism.

PMID- 7645173
TI  - [X-ray anatomy of lacrimal canaliculi].
AB  - Contrast roentgenography of the lacrimal duct using bismuth suspension in 30%
      iodolipol solution in 2:1 ratio was carried out in 48 patients aged 24 to 62, 26
      of them women and 22 men. The mean length of the vertical part of the lacrimal
      canaliculi, both inferior and superior, was found to be 2 mm (from 1.7 to 2.2
      mm), the length of the horizontal portion of the lower lacrimal canaliculus 10 mm
      (from 7 to 13 mm), and that of the horizontal fragment of the upper lacrimal
      canaliculus 9 mm (from 6 to 12 mm). The mean length of the common part of the
      lacrimal canaliculi (after fusion of the two canaliculi in one) was 3 mm (from 1
      to 5 mm). All the examinees had a common portion of the canaliculus. The mean
      total length of the lower lacrimal canaliculus was 14 mm (from 11 to 17 mm), that
      of the upper one 13 mm (from 10 to 16 mm).

PMID- 7645174
TI  - [Results of the treatment method in senile macular dystrophy].
AB  - A new method is offered for surgical treatment of senile central chorioretinal
      dystrophy consisting in trephination of the sclera and implantation into
      subtenon's space of a strip of collagen hemostatic sponge. The author claims that
      this operation promotes development of true collagen bonds between extra- and
      intraocular circulation schemes. An original method of drug administration into
      the zone and of implant fortification to prolong the action thereof is described.

PMID- 7645175
TI  - [Clinical effectiveness of bio-micro-ophthalmoscopy using aspherical high-diopter
      lenses].
AB  - The author presents an optimized method of bio-ophthalmoscopy using new Russian
      aspherical high-diopter lenses +60.0, +75.0, and +90.0 diopters, supplied with
      photoprotective filters. Excellent characteristics of the lenses ensure a perfect
      stereoscopic picture of a large site of the fundus oculi and of the intraocular
      cavity making use of slit lamps of any design. Various chorioretinal
      abnormalities, including the very initial changes, are easily diagnosed. The
      method is rather simple and ergonomic. An appreciable advantage of high-diopter
      aspherical lenses is the possibility of using them in coagulative contact-free
      laser interventions on the fundus oculi, which may be performed, primarily, in
      cases with peripheral abnormalities which are difficult to examine using the
      traditional Goldman's type lenses. Methods of working with the new optical
      elements are described in brief and recommendations on their practical use are
      offered.

PMID- 7645176
TI  - [Pseudopterygium as an outcome of acute gonoblenorrheal conjunctivitis].

PMID- 7645178
TI  - [Eye injuries caused by gas guns].

PMID- 7645177
TI  - [Experience in training in contact correction of vision during an ophthalmology
      course at the Kirov Branch of the Perm Medical Institute].
AB  - The authors analyze the results of one-year activity of a room for contact
      correction of vision at the Ophthalmology Course of the Kirov Branch of the Perm
      Medical Institute. They compare various types of soft contact lenses of different
      make by the following criteria: optical characteristics, variety of mathematical
      parameters, gas permeability, and tolerance of the lens by the eye.
      Recommendations on the choice of this or that lens type (simple soft contact or
      ultrathin lenses) are offered. Complications associated with wearing of soft
      contact lenses are described, which are subdivided into ischemic and allergic,
      their causes are discussed and measures to cope with them presented.

PMID- 7645179
TI  - [Morphological features of vitreoretinal proliferation, complicating dystrophic
      retinal detachment and experimental models].

PMID- 7645180
TI  - [Proxodolol, a new domestic preparation for lowering intraocular pressure in
      glaucoma].
AB  - Effects of a Russian b-a-adrenoblocker proxodolol on the intraocular pressure,
      ocular hemodynamics, pupil diameter, ocular functions, arterial pressure, and
      heart rate were studied in 105 patients (163 eyes) with primary open-angle
      glaucoma. A manifest hypotensive effect of proxodolol was due to depression of
      aqueous humor production and improvement of its outflow. Comparative study of the
      efficacies of proxodolol and timolol maleate by the blind test and randomization
      demonstrated the identity of these drugs. A synergic effect on intraocular
      pressure was observed when proxodolol was combined with pilocarpine and/or
      klofelin.

PMID- 7645182
TI  - Future of the SVS: the Government announces its decision.

PMID- 7645181
TI  - [Use of siflox (ciprofloxacin) in paratrachoma and assessment of its
      effectiveness by immunoenzyme analysis].
AB  - The possibility of using an antibiotic ciprofloxacin quinolone (siflox) in
      combined therapy of paratrachoma was investigated. Fifty patients with acute and
      subacute paratrachoma were included in the study. The drug efficacy was assessed
      by clinical results and laboratory findings: by the time course of the levels of
      Chlamydia trachomatis antigen in smears from the conjunctiva, measured by enzyme
      immunoassay (EIA) using the Abbott kit. The results indicated a high efficacy of
      siflox in combination with local application of tetracycline ointment; such
      treatment helped shorten the treatment period. EIA proved to be not only a highly
      sensitive and effective method for the diagnosis of chlamydial infection of the
      eyes, but permitted assessment of changes in the levels of the antigen over the
      course of treatment and, hence, helped assess the treatment efficacy.

PMID- 7645183
TI  - Slowing the spread of anthelmintic resistant nematodes of horses in the United
      Kingdom.
AB  - The growing importance of anthelmintic resistance in cyathostomes (small
      strongyles) of horses poses a threat to the health and welfare of all types of
      horses. On the basis of published information on cyathostomes of horses, six
      recommendations are made for reducing the development and spread of anthelmintic
      resistant nematodes. The need for restraint in the use of anthelmintics, the
      application of epidemiological principles of worm control and a greater emphasis
      on pasture management are the principal recommendations.

PMID- 7645185
TI  - Protection of maternal endometrium using fetal skin during bovine fetotomy.

PMID- 7645184
TI  - Effect of various levels of T-2 toxin on the clinical status, performance and
      metabolism of growing pigs.
AB  - In two sets of experiments eight groups of seven-week-old pigs weighing about 9
      kg were fed for three weeks a prestarter that contained 0.5, 1.0, 2.0, 3.0, 4.0,
      5.0, 10.0 or 15.0 mg/kg of highly purified T-2 toxin. The feed of the two control
      groups was free from T-2 toxin. Average daily intakes of toxin by the pigs were
      0.38, 0.81, 1.24, 1.43, 0.93, 0.81, 0.99 and 2.5 mg, respectively. The weight
      gains, the feed intakes, the extent of feed refusal, the parameters of energy and
      protein metabolism and the serum concentrations of calcium, inorganic phosphorus
      and magnesium were affected to different extents by the different doses of T-2
      toxin, but the data indicated that feed consumption was reduced and the activity
      of aspartate aminotransferase was increased by the smallest amount of T-2 toxin
      tested.

PMID- 7645186
TI  - CNF1 toxin-producing strains of Escherichia coli isolated from weaner pigs with
      necrotic enteritis in South Africa.

PMID- 7645187
TI  - Prevalence of five serotypes of bluetongue virus in a Rambouillet sheep flock in
      Pakistan.

PMID- 7645189
TI  - Serological study of equine viral arteritis in standard-breds in the UK.

PMID- 7645188
TI  - Sex preselection in cattle: a field trial.

PMID- 7645190
TI  - Canine Lyme disease.

PMID- 7645192
TI  - Greenfinch mortalities.

PMID- 7645191
TI  - Anaemia in housed lambs.

PMID- 7645193
TI  - Changes in oestrogen, progesterone and epidermal growth factor receptor
      concentrations and affinities during the oestrous cycle in the normal mammary
      gland and uterus of dogs.
AB  - Changes in the concentrations and affinities of receptors for oestrogen (ER),
      progesterone (PR) and epidermal growth factor (EGF-R) were studied in mammary
      glands of healthy bitches with regard to age, the location in the mammary chain
      and the stage of the oestrous cycle. Uterus was used as the reference tissue for
      the evaluation of steroid receptors. Mammary and uterine samples from 7 healthy
      bitches were taken at five stages of the oestrous cycle in such a way that all
      the locations in the mammary chain were represented at each stage of the cycle
      (10 samples/dog). ER, PR and EGF-R were detected by biochemical assays using
      increasing concentrations of tritiated (steroids) or iodinated (EGF) ligands. A
      significant direct correlation was found between the ER and PR concentrations for
      mammary and uterine samples. No significant correlation was found between the
      steroid receptors and EGF-R concentrations. Mammary ER concentrations were
      significantly higher in bitches of 5 years of age or older than in younger ones;
      in posterior glands (4th and 5th pairs) than in anterior glands; and in the mid
      luteal phase. Mammary PR did not vary significantly with age or location but was
      significantly lower in the early luteal phase than in other phases. A similar
      decrease in PR concentrations was observed in the uterus during the early luteal
      phase and uterine ER and PR concentrations were very low in the mid-luteal phase.
      Mammary EGF-R were not significantly higher in the early or mid-luteal phase than
      in pro-oestrus or anoestrus. The differences observed between the uterine and
      mammary steroid receptor concentrations during the oestrous cycle could be due to
      different mechanisms for regulating steroid receptor expression in the two
      tissues. Mammary EGF-R concentrations may be linked, as in other species, to
      cellular proliferation and/or to the serum progesterone concentrations.

PMID- 7645194
TI  - Altered adenosine triphosphatase activities in pigs with naturally occurring
      hypertrophic cardiomyopathy.
AB  - The purpose of this study was to determine whether myocardial adenosine
      triphosphatase (ATPase) activities were reduced in pigs with naturally occurring
      hypertrophic cardiomyopathy (HCM). The selection of hearts for the HCM and the
      normal control groups depended on histological examination. Specific ATPase
      activity and 5'-nucleotidase activity were measured in left ventricular
      myocardium obtained from HCM (n = 7) and normal control (n = 7) animals. The
      histological features of HCM included marked disorientation of muscle cells,
      thickening of the intramural coronary arterial wall with a narrowed lumen,
      endocardial fibrosis and myocardial fibrosis. The HCM group showed significant
      increases in both heart weight (32%) and heart weight to body weight ratio (46%).
      The total ATPase activity in crude homogenates from the HCM group was
      significantly decreased by 16%. Azide-sensitive ATPase (mitochondrial ATPase)
      activity, ouabain-sensitive ATPase (Na+, K+-ATPase) activity, basal Mg(2+)-ATPase
      activity and Ca(2+)-ATPase activity were all significantly decreased by 18%, 30%,
      20% and 50%, respectively. In contrast, no significant decrease was found in the
      mean values for 5'-nucleotidase activity. These results suggest that myocardial
      ATPase activities are suppressed in pigs with naturally occurring HCM.

PMID- 7645195
TI  - The prevalence of positive intradermal reactions to paracoccidioidin in domestic
      and wild animals in Sao Paulo, Brazil.

PMID- 7645196
TI  - Studies on the prevalence of the swine kidney worm Stephanurus dentatus in
      Rohilkhand division of Uttar Pradesh (India).

PMID- 7645197
TI  - The effects of physostigmine on the electroretinogram in the beagle dog.
AB  - The purpose of the study was to correlate electroretinogram (ERG) parameters with
      increasing levels of plasma, erythrocyte and ocular tissue cholinesterase
      inhibition using the beagle dog as a model for human neurovisual toxicity. The
      anticholinesterase compound physostigmine was administered at various steady
      state intravenous infusion rates based on pharmacokinetic estimates of plasma and
      red blood cell cholinesterase inhibition. The most sensitive parameter was the b
      wave amplitude of the rod response, which was significantly depressed compared to
      pretreatment at all levels of acute cholinesterase depression. The overall
      maximal ERG response demonstrated a trend of declining a- and b-wave amplitudes,
      which corresponded with the increased levels of cholinesterase depression, but
      these differences were not significant. The depression of the electroretinogram
      rod and cone amplitudes appeared to parallel plasma cholinesterase inhibition
      more closely than erythrocyte cholinesterase activity. Ocular tissue
      cholinesterase activity was significantly depressed in the retina (70%), cornea
      (60%) and dorsal rectus extraocular muscle (46%). Electroretinography may be a
      useful physiological tool for evaluating the ocular toxicity of certain chemicals
      or pharmaceuticals associated with cholinesterase biomarker activity.

PMID- 7645198
TI  - Pentoxifylline pretreatment fails to block the acute-phase response to
      Escherichia coli endotoxin in dwarf goats.
AB  - The purpose of this study was to assess whether pentoxifylline, a drug that can
      inhibit the production and action of pro-inflammatory cytokines, had beneficial
      effects on the acute-phase response to E. coli endotoxin in the dwarf goat.
      First, the effects of 0.5 mg/kg per min pentoxifylline given intravenously over
      15 min were examined in five goats. One week later, the clinical changes caused
      by i.v. injection of E. coli endotoxin (LPS: 0.1 microgram/kg) were determined.
      This endotoxin induced fever, tachycardia, inhibition of rumen motility, and
      decreases in plasma zinc and iron concentrations. Three weeks later, the effect
      of E. coli LPS were again determined immediately after pentoxifylline infusion in
      the same group of animals. It was concluded that a pharmacological dose of
      pentoxifylline has no protective effects on the acute-phase response reactions
      induced by a pyrogenic dose of E. coli LPS.

PMID- 7645199
TI  - A comparison of plasma metabolite levels in goats and sheep during continuous low
      level administration of fenbendazole.
AB  - Plasma levels of fenbendazole (FBZ) and its sulphoxide (OFZ) and sulphone
      (FBZ.SO2) metabolites were measured in goats and sheep during low-level
      administration of FBZ given by intraruminal infusion or formulated into a urea
      molasses feed supplement block (UMB). In experiment 1, 6 goats and 6 sheep were
      offered UMB containing 0.5 g FBZ/kg (MUMB) and individual block consumption was
      measured daily for 18 days. In experiment 2, some of the same animals (n = 4 for
      each species) received FBZ by intraruminal infusion at 1, 1.5 and 3 mg/kg
      liveweight per day for 7 days at each dosage. FBZ, OFZ and FBZ.SO2 levels were
      determined in plasma collected every 3 days in experiment 1 and on days 4, 5 and
      6 of each infusion period in experiment 2. In both experiments, higher
      equilibrium levels were observed for the three metabolites in sheep than in
      goats. Significant linear relationships were observed between the daily FBZ
      dosages and the plasma levels of the three metabolites in both species. The
      regression coefficients were significantly higher in sheep than in goats for FBZ
      and OFZ but not for FBZ.SO2, and they were also significantly higher during MUMB
      administration than during infusion for all three metabolites in both species.
      FBZ is a suitable anthelmintic for incorporation into a MUMB formulation for use
      in livestock production systems where responses to molasses urea supplementation
      have been demonstrated and gastrointestinal parasitism impairs productivity. The
      results indicate that target dose rates for goats should be 0.75 mg/kg per day
      compared with 0.5 mg/kg per day for sheep.

PMID- 7645201
TI  - Changes in the serum concentrations of gonadotrophins and oestradiol in
      peripubertal Chinese Beijing black gilts.
AB  - Four gifts of the Chinese Beijing Black breed, all from the same litter, had
      their blood serum concentrations of luteinizing hormone (LH), follicle
      stimulating hormone (FSH) and oestrogens (E2) measured by radioimmunoassay at
      intervals of 20 days between the ages of 5 and 185 days. The concentrations of LH
      declined sharply between days 5 to 25 and remained low until rising again from
      day 85 and reaching a peak at day 105 before declining again and remaining
      constant. The concentrations of FSH increased from day 85, peaking at day 105,
      followed by a slow decline to day 185. Serum E2 concentrations were high at day 5
      then decreased dramatically, but increased considerably at 185 days. These
      results are similar to those reported from European breeds.

PMID- 7645200
TI  - Muscular architecture and VIP-like immunoreactive nerves in the gastroduodenal
      junction of the chicken.
AB  - The muscular architecture and the distribution of nerves with vasoactive
      intestinal polypeptide-like (VIP-like) immunoreactivity were examined in the
      gastroduodenal junction of the chicken. Both the outer and the inner muscle
      layers (tunica muscularis) and the muscularis mucosae were examined. The inner
      muscle layer was divided into two parts, namely its inner and outer parts. The
      outer muscle layer was not present in the pyloric part but was found in the
      proventriculus and the duodenum. The muscle strands of the outer muscle layer ran
      longitudinally but were absent at the isthmus and the pylorus. Most of the outer
      part of the inner muscle layer was located in or close to the pyloric part. The
      muscle strands in the outer part connected the pyloric part with other regions,
      namely the craniodorsal muscle, the tendinous centres and the isthmus. The inner
      part of the inner muscle layer was widely distributed in the stomach. In the
      pyloric part, the muscle strands of this layer followed a circular or spiral
      course. The muscularis mucosae was not present in the caudodorsal and
      cranioventral muscles of the gizzard. In addition, VIP-like immunoreactive nerve
      fibres were predominantly distributed in the inner part of inner muscle layer of
      the pyloric part. These results suggest that the ventriculopyloric orifice and
      the pyloric part itself constrict with a sphincter-like action.

PMID- 7645202
TI  - Mutational analysis of a putative NTP-binding domain in the replication
      associated protein (AC1) of bean golden mosaic geminivirus.
AB  - Bean golden mosaic virus (BGMV) is a whitefly-transmitted, ssDNA geminivirus with
      a bipartite genome. AC1 is the only ORF required for geminiviral replication. A
      putative NTP-binding motif, EGX4GKTX32DD, was present in the derived amino acid
      sequence of the replication-associated protein from the AC1 ORF for 13
      geminiviruses including BGMV-GA (Guatemalan isolate, amino acids 221-263). We
      analyzed the phenotypes of mutations within this domain using a rapid and
      sensitive PCR-based assay for geminiviral replication developed for these
      studies. Replication in tobacco cells (NT-1 suspension cells) and infection of
      beans were abolished when codons were changed from K228 to H or D262 to R within
      the putative NTP-binding site. A temperature-sensitive replication phenotype was
      conferred by changing E221 to R within the putative NTP-binding domain.
      Replication was unaffected by changing a nonconserved codon near the putative NTP
      binding domain from 1190 to R. Our results demonstrate that the putative NTP
      binding domain is required for geminiviral replication. The role of NTP
      hydrolysis and the possible value of these mutants in a trans-dominant
      interference scheme for virus-derived resistance are discussed.

PMID- 7645203
TI  - Murray valley encephalitis virus envelope protein antigenic variants with altered
      hemagglutination properties and reduced neuroinvasiveness in mice.
AB  - Neutralization escape variants of Murray Valley encephalitis virus were selected
      using a type-specific, neutralizing, and passively protective anti-envelope
      protein (E) monoclonal antibody (4B6C-2) which defines epitope E-1c. Nucleotide
      sequence analysis revealed single nucleotide changes in the E genes of 15
      variants resulting in nonconservative amino acid substitutions in all cases. One
      variant had a three-nucleotide deletion in the E gene which resulted in loss of
      serine at residue 277. Changes were clustered into two separate regions of the E
      polypeptide (residues 126-128 and 274-277), indicating that E-1c is a
      discontinuous epitope. One variant (BHv1), altered at residue 277 (Ser-->Ile),
      failed to hemagglutinate across the pH range 5.5-7.5, in contrast to parental
      virus and the other escape variants which hemagglutinated at an optimal pH of
      6.6. BHv1 was also of reduced neuroinvasiveness in 21-day-old mice following
      intraperitoneal inoculation compared to the other viruses. Parental virus and the
      neutralization escape variants grew equally well in both vertebrate and
      invertebrate cell cultures, indicating that the reduced neuroinvasiveness of BHv1
      was not due to a major abnormality of replication.

PMID- 7645204
TI  - Induction of humoral and cellular immune responses to the human immunodeficiency
      type 1 virus in nonhuman primates by in vivo DNA inoculation.
AB  - DNA inoculation has the potential to produce antigens in a native as well as a
      host-"customized" form for presentation to the immune system. As such this
      technology may have relevance for vaccine/immune therapeutic strategies for a
      variety of infectious pathogens. In rodents in vivo inoculation of plasmid
      expression vectors encoding HIV-1 gene products leads to production of HIV-1
      antigens in vivo, resulting in the production of both cellular and humoral immune
      responses. In primates only preliminary studies of serology have been reported.
      Here we report further evaluation of this new technology as a method to induce
      humoral and particularly cellular immune responses against a human pathogen, the
      HIV-1 virus, in nonhuman primates. Following inoculation and boosting of animals
      with an HIV gp160 plasmid expression vector we observed the induction of
      neutralizing responses against two diverse HIV-1 isolates in 2 of 3 vaccinated
      animals. T cell proliferative responses to HIV antigens were also observed in all
      plasmid-inoculated animals and specific cross-reactive cytotoxic T lymphocyte
      responses were developed in vaccinated animals. This report establishes the
      ability of DNA inoculation to induce cellular immune responses in nonhuman
      primates and suggests that further investigation of this technology with regard
      to human vaccine or immune therapeutic development is therefore warranted.

PMID- 7645205
TI  - Cells resistant to interferon-beta respond to interferon-gamma via the Stat1-IRF
      1 pathway.
AB  - The mechanism responsible for the induction of the 2-5A synthetase gene by
      Interferon-gamma (IFN-gamma) (type II) was studied in Friend leukemia cells. It
      was previously shown that activation of 2-5A synthetase gene expression by IFN
      gamma in the 3Cl8 cell, a clone resistant to IFN-alpha,beta (type I), correlates
      with the formation of two major complexes, designated Fg and Fc, that bind to the
      interferon-stimulated responsive element of the gene. Conversely, in a clone
      resistant to both types of IFNs (3 gamma R8), no induction of DNA-protein
      complexes or of 2-5A synthetase gene expression was detected. In the present
      report the Fg complex has been characterized as including the interferon
      regulatory factor 1 (IRF-1), whereas the Fc factor, present also in control
      cells, has been characterized as composed of IRF-2. Incubation of cell extracts
      with antibodies to IRF-1 abolishes the formation of the Fg complex, and
      antibodies to IRF-2 abolish the formation of the Fc complex. Moreover, in the
      3Cl8 cell, IFN-gamma is able to induce in few minutes the formation of a complex
      between a DNA element identified as the IFN-gamma activation site (GAS), present
      on the IRF-1 gene promoter, and the STAT1 protein. These findings suggest that in
      cells resistant to type I IFN, IFN-gamma is able, through the activation of the
      STAT1 protein, to induce the expression of the IRF-1 factor which in turn seems
      to be sufficient to transactivate the 2-5A synthetase gene.

PMID- 7645207
TI  - The mechanism of natural occurrence of two closely linked HBV precore predominant
      mutations.
AB  - Two precore predominant mutations of human hepatitis B virus (HBV) at either
      nucleotide (nt) 1896 or nt 1899 often occur in combination. At nt 1896, a G to A
      mutation creates a TAG stop codon at codon 28 of precore protein. At nt 1899, a G
      to A mutation changes glycine at codon 29 to aspartic acid. To assess the effect
      of each individual mutation as well as any interaction between these two
      mutations, HBV derivatives bearing one or both precore predominant mutations have
      been constructed. HBV e-Ag-negative mutants bearing a TAG stop codon mutation at
      codon 28 uniformly replicate at least 20-fold better than mutants bearing a TGA
      stop codon at the same amino acid position, irrespective of the sequence context
      at nt 1899. A single mutation at nt 1899, changing the wild-type G to a
      pyrimidine (T or C) is deleterious to viral RNA encapsidation and DNA
      replication. Our results explain in part why only a purine (G or A) at nt 1899,
      never a pyrimidine, is observed in natural HBV genomes. The effects caused by
      these two closely linked mutations on viral replication are not independent of
      each other. The stringent selection for a highly efficient RNA encapsidation
      element may play a crucial role in the natural occurrence of these two closely
      linked precore mutations. The putative 27-amino-acid peptide resulting from the
      truncation of precore by the nt 1896 mutation has no apparent effect on viral
      replication. The preferential occurrence of the G to A mutation at nt 1896 and
      1899, instead of at other nonpredominant positions, is likely to be a combined
      consequence of both selection and higher intrinsic mutation frequency at these
      positions.

PMID- 7645206
TI  - Analysis of the cell and erythrocyte binding activities of the dimple and canyon
      regions of the canine parvovirus capsid.
AB  - Canine parvovirus (CPV) binds to a number of cell and erythrocyte receptors, some
      of which are involved in cell infection, while others are used for other viral
      functions. Little is known about the regions of the virus capsid which bind to
      the cell receptors. CPV binds sialic acid through a region within or adjacent to
      the dimple on the surface of the capsid (Barbis, D. P., Chang, S-F., and Parrish,
      C. R., 1992, Virology 191, 301-308). In order to map the sialic acid binding site
      in more detail and to examine other regions of the capsid for cell receptor
      binding, a variety of mutant capsids were analyzed which had changes in two
      depressions within the surface of the capsid--the "canyon" and "dimple." In most
      cases recombinant VP1 and VP2 proteins were stably expressed together in canine
      A72 cells from a plasmid expression vector. The purified empty capsids were
      tested for their ability to bind sialic acid and thereby hemagglutinate (HA)
      erythrocytes and for binding to permissive host cells. In addition, the ability
      of neutralizing monoclonal antibodies to block cell attachment was also examined.
      Mutations of amino acids on a wall of the dimple eliminated or severely decreased
      HA. Changing various residues within the canyon had no effect on binding to
      either sialic acids or other receptors on feline lymphoblastoid cells, suggesting
      that the canyon is not the site of cell receptor attachment. Neutralizing
      monoclonal antibodies against both major antigenic determinants had variable
      effects on cell binding, but no consistent inhibition of binding was observed by
      antibodies directed against either of those two major antigenic determinants of
      the capsid.

PMID- 7645208
TI  - Infection and replication of Tat- human immunodeficiency viruses: genetic
      analyses of LTR and tat mutations in primary and long-term human lymphoid cells.
AB  - Tat is an essential regulatory protein for the replication of human
      immunodeficiency virus (HIV). Mutations in the tat gene have been shown to block
      HIV replication in human T cells. Several studies have established that Tat
      releases an elongation block to the transcription of HIV long terminal repeat
      (LTR); however, it is not known whether this mechanism alone is sufficient to
      explain the block to HIV replication in human T cells when Tat is absent. It is
      possible that Tat is also needed for other functions during HIV replication. To
      test these hypotheses, we studied several tat mutants, including two stop codon
      mutants and one deletion mutant using replication-competent HIV-1 constructs
      carrying wild-type or mutant LTRs with modifications in the NF-kappa B and/or Sp1
      binding sites. In this study, we show that Tat- HIV-1 with wild-type LTRs can
      replicate in HeLa cells, and the virus produced from HeLa cells can infect
      primary peripheral blood lymphocytes and macrophages. It was found that the
      propagation of the Tat mutants containing wild-type LTRs was less efficient than
      that of the LTR-modified Tat mutants. Large amounts of viral RNA and particles
      were synthesized in infections established using the tat mutants that contain
      modified LTRs. However, this efficient propagation of the LTR-modified tat
      mutants was restricted to some lymphoid cell lines that have been transformed
      with other viruses. Thus, despite its essential role for releasing an elongation
      block, Tat is not otherwise absolutely required for synthesis of full-length HIV
      transcripts and assembly of virus particles. Direct sequencing of the viral
      genomes and reinfection kinetics showed no evidence of wild-type reversion even
      after prolonged infection with the Tat- virus. The implications for in vivo HIV-1
      replication and potential application of this system to the study of alternative
      Tat function are discussed.

PMID- 7645209
TI  - Nicotiana benthamiana plants transformed with the 54-kDa region of the pepper
      mild mottle tobamovirus replicase gene exhibit two types of resistance responses
      against viral infection.
AB  - Nicotiana benthamiana plants transformed with the 54-kDa region of the pepper
      mild mottle tobamovirus (PMMV) replicase gene were generated and six
      independently transformed plant lines were analyzed for resistance to PMMV. Two
      different resistance responses were obtained. Some of the transgenic plants from
      only two lines showed a preestablished, complete, and highly resistant phenotype
      since no viral symptoms were observed, although a low level of virus replication
      occurred. The remaining plants from these two lines and all of the plants from
      the other four lines tested showed a delayed, induced, and also highly resistant
      phenotype since they were susceptible early, but were able to recover from the
      systemic PMMV infection. Recovered, symptomless leaves were resistant to the PMMV
      strain from which the 54-kDa gene was derived and to a closely related strain but
      not to tobacco mosaic virus. Such a delayed resistance phenotype has not been
      previously described for any plant expressing viral replicase sequences. The
      transgenic plants within the lines displaying complete or delayed resistance
      phenotypes were analyzed for transgene expression before and after PMMV
      inoculation and the two types of resistance responses were shown to be
      independent of the transgene transcript level.

PMID- 7645210
TI  - Transcriptional activity of human papillomavirus type 31b enhancer is regulated
      through synergistic interaction of AP1 with two novel cellular factors.
AB  - Transcription of human papillomaviruses (HPV) is regulated by enhancer sequences
      located in the upstream regulatory region. The factors regulating expression of
      one of the high risk genital HPV types, HPV 31b, were investigated using
      transient expression and protein binding assays. A region of 262 base pairs in
      length was identified as the minimal functional enhancer and a series of five
      protected binding sites were observed by footprint analyses. Electrophoretic
      mobility shift assays demonstrated that AP1, Oct-1, as well as three novel
      factors bound these sequences. Mutational analyses indicated that AP1
      synergistically activated the HPV31b enhancer together with either of two novel
      factors. One of these novel factors bound a sequence similar to an NF1 site but
      was distinct from NF-1. The second factor bound sequences bearing similarity to
      KRF-1 binding sites which have previously been characterized in HPV 18.
      Competition binding assays demonstrated that this factor was not identical to KRF
      1. Additional studies implicated Oct-1 as a negative regulator of HPV 31b
      expression as mutation of Oct-1 binding sequences resulted in an increase in
      viral expression. None of the factors observed to be important for HPV 31b
      enhancer activity was found exclusively in epithelial cells and instead were
      detected in a variety of cell types. Of these factors, AP1 binding correlated
      most strongly with enhancer function in a variety of cell types, implicating it
      as a principal regulator of HPV expression. Variations in the constituents of the
      AP1 complex that bind the HPV 31b enhancer were also observed in different cell
      types, suggesting that changes in the distribution of jun proteins may play a
      significant role in determining the tropism of HPV. These results indicate that
      AP1 may be a common regulator for various HPV types and that it contributes to
      enhancer specificity. In addition, a set of novel factors, which may be specific
      for each HPV type, act synergistically with AP1 for full activation of the
      enhancer.

PMID- 7645211
TI  - Sequence distances between env genes of HIV-1 from individuals infected from the
      same source: implications for the investigation of possible transmission events.
AB  - Previously described transmission studies have shown that HIV strains isolated
      from individuals infected from a common source are more homogeneous than HIV
      strains isolated from individuals with unrelated infections. This has been the
      basis, in at least four instances, for deciding whether apparently
      epidemiologically related cases represent actual transmissions. To date, HIV
      transmission studies have usually included sequence data from the most likely
      source of infection, and the probability of transmission from the donor to the
      recipient has been assessed by measuring sequence similarity against control data
      using likelihood analysis. We have recently studied a putative transmission
      involving a UK health care worker (CPHL1), a patient of CPHL1 (CPHL2), and CPHL3,
      a member of the same "sex circle" as CPHL2. We have used sequence distance and
      neighbour joining methods as well as likelihood analysis as means of determining
      genetic relatedness. Though no other source of infection was available our
      findings did not support the possibility that CPHL1 had infected CPHL2. Strain
      CPHL3 was closer to CPHL2 than to CPHL1. It is shown that control data from
      documented transmission events can be used to establish the source of infection
      in the absence of an index case. It is also shown that the C2-V3 region analysed
      in previous transmission studies is unreliable for accurate phylogenetic
      analysis. The results indicated that gp120 is a more informative region than C2
      V3 for molecular transmission studies. Sequence distances between the env genes
      of related and unrelated infections have been derived in this work.

PMID- 7645212
TI  - Influence of the host cell on the association of ICP4 and ICP0 with herpes
      simplex virus type 1.
AB  - ICP4 and ICP0 are two immediate-early proteins of herpes simplex virus type 1
      associated with the transcriptional activation of viral genes within infected
      cells. Previous studies in our laboratory have shown that approximately 100-200
      molecules each of ICP4 and ICP0 are associated with the tegument region of
      virions purified from Vero and HEp-2 cells (F. Yao and R. J. Courtney, 1989, J.
      Virol. 63, 3338-3344 and 1992, J. Virol. 66, 2709-2716). However, other studies
      have shown that ICP4 molecules are primarily associated with non-capsid
      containing light (L) particles obtained from BHK-21 cells and purified by 5-15%
      continuous Ficoll gradients (J. McLauchlan and F. J. Rixon, 1992, J. Gen. Virol.
      73, 269-276). To reconcile these findings with regard to the association of
      immediate-early protein with virions obtained from different cell lines, our
      studies have focused on determining if the host cell type influences the amounts
      of ICP4 and ICP0 associated with the capsid-containing heavy (H) virus particles
      (purified virions) compared to the amounts associated with L particles. Virus
      particles were purified from three different cell lines, Vero, HEp-2, and BHK-21
      cells. The H and L virus particles were resolved on 5-15% Ficoll gradients. The
      results presented indicate that although ICP4 and ICP0 are readily detectable in
      H particles obtained from Vero and HEp-2 cells, minimal amounts of ICP4 and ICP0
      are associated with H particles obtained from BHK-21 cells. The data suggest that
      the host cell may influence the relative amounts of ICP4 and ICP0 associated with
      the tegument region of virus particles. Finally, physical particle counts of the
      H and L particles also suggest that the host cell influences the relative number
      of L particles produced within the cell.

PMID- 7645213
TI  - Nucleotide sequence and transcription of the left early region of Streptococcus
      pneumoniae bacteriophage Cp-1 coding for the terminal protein and the DNA
      polymerase.
AB  - Cp-1 is a small virulent bacteriophage infecting Streptococcus pneumoniae. It has
      a linear, double-stranded genome of about 19 kb that replicates by a protein
      priming mechanism. We have determined the nucleotide sequence of the leftmost
      4780 bp of the DNA of this bacteriophage; computer analysis revealed that this
      fragment contains seven open reading frames (ORFs) which could encode
      polypeptides containing more than 50 amino acids. The ORFs are clustered in two
      groups separated by noncoding intergenic regions. Two of these ORFs code for the
      terminal protein and a specific DNA polymerase that participate in the
      replication of the DNA. The predicted amino acid sequence of the terminal protein
      shows significant similarity with the terminal protein of Bacillus subtilis phage
      phi 29, and Cp-1 DNA polymerase is homologous to the subgroup of eukaryotic-type
      DNA polymerases that use a protein as a primer. Combined Northern blots and
      primer extension experiments have allowed us to map the 5' initiation sites of
      left early transcripts. These studies revealed that transcripts elongate from
      left to right and identified the left early promoters.

PMID- 7645214
TI  - Involvement of cellular casein kinase II in the phosphorylation of measles virus
      P protein: identification of phosphorylation sites.
AB  - The phosphoprotein P gene of measles virus (Edmonston strain) has been cloned in
      the Escherichia coli expression vector pET-3a with a histidine tag at the C
      terminal end. The expressed protein was soluble, unphosphorylated, and
      constituted 10 to 20% of total cellular protein. Recombinant P protein purified
      by Ni-affinity chromatography was found to be efficiently phosphorylated in vitro
      by recombinant casein kinase II (CKII) or by the CKII activity present in the
      uninfected cell extract. A comparison of phosphopeptide analyses between the in
      vivo- and the in vitro-32P-labeled P proteins revealed that both proteins share
      common phosphorylation sites. In an attempt to identify the exact site of the
      CKII-mediated phosphorylation, we altered specific serine residues located within
      the CKII consensus motif to alanine by site-directed mutagenesis. The results
      indicate that Ser 86, Ser 151, and Ser 180 located within the N-terminal half of
      the P protein are involved in the CKII-mediated phosphorylation of the P protein.

PMID- 7645215
TI  - The HPV16 E5 protein: expression, detection, and stable complex formation with
      transmembrane proteins in COS cells.
AB  - The human papillomavirus-16 (HPV16) E5 gene is able to induce stable growth
      transformation and transient mitogenic stimulation in a variety of cultured cell
      systems. To characterize the biochemical properties of the hydrophobic HPV16 E5
      transforming protein, we have constructed vectors expressing the wild-type HPV16
      E5 gene and have generated antipeptide antisera. The 10-kDa E5 protein was
      readily detectable in transfected COS monkey cells by using these antisera either
      for immunoprecipitation of metabolically labeled cells or for immunoblotting.
      Coimmunoprecipitation analysis of cells coexpressing the viral protein and
      various growth factor receptors demonstrated stable complex formation between the
      E5 protein and the epidermal growth factor receptor, platelet-derived growth
      factor beta receptor, colony stimulating factor-1 receptor, and p185neu. The E5
      protein also formed a stable complex with the vesicular stomatitis virus
      glycoprotein. These experiments indicated that the HPV16 E5 protein was able to
      participate in complex formation with a variety of transmembrane proteins, a
      property which may contribute to the biological activities of the viral protein.
      In addition, the expression vectors and antibodies described here will be useful
      reagents in examining various aspects of HPV16 E5 expression and function.

PMID- 7645216
TI  - Virofection: a one-step procedure for using replication-defective retrovirus
      vectors.
AB  - Virofection is a simple new way to use replication-defective vectors. It consists
      of the cotransfection of two plasmids: one plasmid bearing the genome of the
      replication-defective retrovirus vector and a second "helper" plasmid expressing
      the gag, pol, and env retrovirus sequences. It provides stable integration into
      the chromosome and long-term expression of only vector-borne sequences. We
      present here several helper plasmids derived from avian leukosis viruses, which
      we have used for the virofection of the lacZ reporter gene in chicken cell
      cultures. Expression can be stabilized at a very high rate in both chicken
      fibroblasts and blastoderm cells, without giving rise to replication-competent
      virus.

PMID- 7645217
TI  - Homodimeric association of the spike glycoproteins G1 and G2 of Uukuniemi virus.
AB  - We have studied the interactions of the G1 and G2 membrane glycoproteins of
      Uukuniemi virus, a bunyavirus, in virus particles and in Triton X-100-solubilized
      virus. The G1 glycoprotein in intact virus or in Triton solution could be
      oxidized into a covalent homodimer using Cu2+ ion as a catalyst.
      Immunoprecipitations of the glycoproteins from Triton-solubilized virus lysates
      showed that G1 and G2 do not form a stable heterodimeric or heterooligomeric
      complex. The oligomeric association of G1 and G2 was further analyzed using
      centrifugation in sucrose gradients in the presence of Triton X-100. The results
      indicate that G1 exists as a Triton-resistant pH-insensitive homodimer. This is
      in contrast to the behavior of G2, which exists as a homodimer and partially as a
      monomer at pH 6.4 or above and is dissociated completely into a monomer at pH 6.0
      or below. The threshold for the dimer-monomer shift of G2 is between pH 6.2 and
      pH 6.0. Electron microscopy studies show that the surface structure of the virus
      particle undergoes a pH-dependent change. Studies on the kinetics of virus entry
      suggest that pH below 6.2 is necessary for the penetration of Uukuniemi virus.

PMID- 7645218
TI  - Interferon-alpha inhibits the murine cytomegalovirus immediate-early gene
      expression by down-regulating NF-kappa B activity.
AB  - Transcription of murine cytomegalovirus (MCMV) immediate-early (IE) genes is
      regulated by the interaction of cellular transcription factors with a strong
      viral enhancer controlling promoters flanking both sides of the regulatory
      sequence. We have previously demonstrated that interferon-alpha (IFN-alpha)
      inhibits MCMV replication by impairing the transcription of IE genes. To define
      the cis-acting elements and trans-acting factors involved in this inhibition,
      permissive murine fibroblasts were transferred with DNA constructs containing the
      chloramphenicol acetyl transferase reporter gene and portions of the IE enhanced.
      The region spanning -1185 to -259 relative to the IE1-3 promoter was sufficient
      to allow IFN-alpha-induced inhibition. Since this segment contains several NF
      kappa B sites, cells were transfected with a construct containing three copies of
      NF-kappa B element in front of the homologous minimal IE1-3 promoter. Upon IFN
      alpha treatment the reporter gene activity was strongly reduced, indicating that
      NF-kappa B binding site is sufficient to confer inhibition. The specificity of
      this inhibition was demonstrated by the lack of a significant effect on the
      activity of DNA constructs containing either a mutated NF-kappa B trimer or an
      ATF/CRE trimer. Gel shift assays with NF-kappa B probes revealed that MCMV
      infection activated NF-kappa B proteins, whereas IFN-alpha treatment
      significantly reduced their ability to bind NF-kappa B sites. In cotransfection
      experiments using various NF-kappa B subunit expression vectors and a reporter
      driven by three copies of an NF-kappa B element, activation of NF-kappa B
      dependent transcription was observed with expression of p65 or combinations of
      p50-p65. Taken as a whole, these results suggest that IFN-alpha inhibits MCMV IE
      gene enhancer activity by mechanisms that decrease the availability of virus
      induced NF-kappa B transcriptionally active in the nuclei of infected cells.

PMID- 7645219
TI  - Cross-reactive cytotoxic T lymphocytes induced by V3 loop synthetic peptides from
      different strains of human immunodeficiency virus type 1.
AB  - Recent efforts at understanding the immune response generated against human
      immunodeficiency virus (HIV) infection have focused on cytotoxic T lymphocyte
      (CTL)-mediated recognition of HIV antigens. CTLs are a major immune defense
      mechanism and are necessary for the recovery of many viral infections. We have
      previously developed a method for screening synthetic peptides for the ability to
      induce virus-specific major histocompatibility complex-restricted CTLs in mice.
      Using this method, we now report the identification of peptides from the V3
      region in gp120 of seven different HIV-1 strains that are capable of inducing a
      virus-specific CD8+ CTL response in vivo. V3 peptides from MN and SC strains of
      HIV-1, which are representative of typical strains found in North America and
      Europe, induced CTLs that exhibited cross-reactivity against a broad range of HIV
      1 strains. In addition, immunization of mice with a mixture of these V3 peptides
      resulted in efficient CTL responses directed against the corresponding HIV-1
      strains. These data, together with information in the literature describing the
      CTL epitope nature of V3 peptide from HIV-1 IIIB in the context of several HLA
      alleles, indicate the possibility of including V3 synthetic peptides as
      components of potential vaccines for inducing broadly cross-reactive CTL response
      against a diverse array of HIV-1 strains.

PMID- 7645221
TI  - Red cells bound to influenza virus N9 neuraminidase are not released by the N9
      neuraminidase activity.
AB  - Influenza virus neuraminidase (NA) of the N9 subtype also possesses hemagglutinin
      activity and the hemagglutinating, or hemabsorbing (HB), site is distinct from
      the catalytic site. Previous results suggested that the NA was binding to sialic
      acid on the red cell surface, but we now report that the HB receptor is not
      sensitive to N9 influenza neuraminidase activity. Cell lines that constitutively
      express N9 or N2 neuraminidase have been used to further investigate the
      specificity of red blood cell binding to the HB site. The results suggest that
      the ligand is N-acetylneuraminic acid in a linkage or environment that is not
      sensitive to influenza virus neuraminidase, but which is released by the broadly
      specific bacterial sialidases from Micromonospora viridifaciens or Arthrobacter
      ureafaciens.

PMID- 7645220
TI  - Identification of adenovirus E1A regions which affect MHC class I expression and
      susceptibility to cytotoxic T lymphocytes.
AB  - To map and characterize functional differences between the E1A oncoproteins of
      Ad5 and Ad12, we previously constructed a series of hybrid Ad5/12 E1A genes and
      used them in combination with Ad12 E1B to transform Hooded Lister rat cells. At
      least two regions within the first exon of Ad12 E1A which influenced
      tumorigenicity were identified. In this report, again using the hybrid Ad5/12 E1A
      (plus Ad12 E1B) transformants, we further examined the role of these regions in
      tumorigenicity by analyzing their effect on cell surface major histocompatibility
      complex class I expression and sensitivity to class I-restricted CD8+ cytotoxic T
      lymphocytes (CTLs). Results of these studies suggest that expression of either of
      the Ad12 E1A regions implicated in tumorigenicity could down-regulate cell
      surface class I levels. However, neither class I down-regulation nor sensitivity
      to allogeneic CTLs was shown to strictly correlate with the tumorigenic
      capacities of the transformed rat cells. Another factor influencing the
      tumorigenicity of Ad5 E1 and Ad12 E1 transformants may be the ability of their
      E1A products to encode CTL epitopes. To this end, we provide evidence suggesting
      that CTL epitopes may be encoded by Ad5 E1A but not by Ad12 E1A, since expression
      of certain portions of the Ad5 E1A protein conferred susceptibility to syngeneic
      Ad5 E1-specific CTLs in vitro, while Ad12 E1A expression did not confer
      susceptibility to syngeneic Ad12 E1-specific CTLs.

PMID- 7645222
TI  - Analysis of cysteine mutations on the transmembrane protein of Moloney murine
      leukemia virus.
AB  - Earlier studies of murine leukemia viruses (MuLVs) have reported that a
      percentage of surface protein (SU) remains covalently associated with
      transmembrane protein (TM) through formation of disulfide bonds. Among MuLVs,
      there are three conserved cysteine residues within the extracellular domain of
      TM. These cysteine residues were substituted individually with serines to define
      their function and possible role in disulfide bonding with SU. Using
      oligonucleotide-directed mutagenesis, seven mutant constructs were generated with
      individual as well as multiple cysteine mutations. Transient transfection of all
      seven cysteine mutations resulted in nonviable virus. Analysis of intracellular
      proteins of producer mutant cell lines have demonstrated that precursor envelope
      protein (gPr80env; SU/TM) is being synthesized, but transport and processing of
      gPr80env is blocked in the endoplasmic reticulum. Two independent reversions of
      one cysteine mutation have been isolated and characterized.

PMID- 7645223
TI  - The activation domain of simian immunodeficiency virus SIVmac239 Rev protein is
      structurally and functionally analogous to the HIV-1 Rev activation domain.
AB  - The Rev proteins of primate immunodeficiency viruses are essential
      transactivators for the switch from early to late phase in the viral replication
      cycle. By mutational analysis, a putative activation domain (AD) has been
      assigned to the carboxy-terminus. This leucine-rich stretch of amino acids proved
      to be essential for the transactivating properties of HIV-1 Rev. Some mutants in
      the AD transdominantly inhibit the function of wild-type Rev protein very
      efficiently. We identified a similar domain structure for SIVmac239 Rev by
      sequence comparison and in vitro mutagenesis. The leucine/isoleucine residues of
      the SIVmac239 Rev activation domain appeared to be of similar importance for
      function. The mutants of these residues in the SIV AD displayed a dominant
      negative phenotype on both HIV-1 and SIVmac 239 rev-responsive elements (RRE).
      The prokaryotically expressed wild-type and mutant proteins were analyzed for RNA
      binding properties in a gel-shift assay in vitro. This assay revealed a similar
      binding pattern of wild-type and transdominant proteins on either RRE.

PMID- 7645224
TI  - Mx1 but not MxA confers resistance against tick-borne Dhori virus in mice.
AB  - The interferon-induced nuclear Mx1 protein is responsible for innate resistance
      of mice to influenza virus. It has been unclear why mice are equipped with a
      powerful and specific defense mechanism against influenza viruses for which they
      are not natural hosts. Here, we show that Dhori virus, an influenza-like virus
      transmitted by ticks and known to infect small mammals, is sensitive to the Mx1
      resistance mechanism. Influenza virus-susceptible BALB/c and C57BL/6 mice
      (lacking a functional Mx1 gene) developed severe disease symptoms and died within
      a few days after intraperitoneal infection with a lethal dose of Dhori virus. In
      contrast, Mx1(+)-congenic, influenza virus-resistant BALB.A2G-Mx1 and B6.A2G-Mx1
      mice remained healthy and survived. The Mx1 resistance phenotype was expressed in
      cultured peritoneal macrophages and interferon-treated embryonic cells obtained
      from these mice. Moreover, stable lines of transfected mouse 3T3 cells
      constitutively expressing Mx1 protein were protected from Dhori virus infection.
      The MxA protein of human cells shows a high degree of sequence similarity to Mx1
      but, unlike Mx1, inhibits a broad range of RNA viruses. Transgenic mice that
      permanently express the human MxA protein in various organs became resistant to
      infection with Thogoto virus but remained fully susceptible to Dhori virus. These
      in vivo results show that DHO virus is unique in being resistant to human MxA but
      susceptible to mouse Mx1 protein. They further indicate that the Mx1 system
      functions as a potent defense mechanism against tick-borne influenza-like viruses
      in mice.

PMID- 7645225
TI  - Egg fluids and cells of the chorioallantoic membrane of embryonated chicken eggs
      can select different variants of influenza A (H3N2) viruses.
AB  - Growth of influenza viruses in embryonated eggs frequently results in the
      selection of virus variants with amino acid changes near the receptor-binding
      pocket of the hemagglutinin molecule, yet the mechanism by which this third form
      of influenza variation occurs (the other two being antigenic drift and shift) has
      not been clearly defined. Because egg-mediated variation might affect influenza
      vaccine and surveillance programs, we have initiated studies to determine the
      site(s) of variant virus selection within the embryonated egg. In this report we
      show that both the cells of the chorioallantoic membrane (CAM) and the fluids
      from embryonated chicken eggs are capable of selecting variant influenza viruses,
      but that these variants are distinct at the molecular level depending on the
      conditions of virus propagation. Serial passage of viruses in cells of the
      chorioallantoic membrane selects one set of variants which possess specific amino
      acid changes near the receptor binding pocket of the hemagglutinin molecule
      characteristic of viruses grown in embryonated eggs. However, passage of the same
      viruses in mammalian tissue culture cells supplemented with egg fluids selects a
      separate set of hemagglutinin variants also characteristic of viruses grown in
      eggs, yet at different residues from those observed following passage in CAM.
      These results suggest that two separate mechanisms may exist in the embryonated
      egg that lead to the selection of variant influenza viruses: one at the cellular
      level and another at the extracellular level.

PMID- 7645226
TI  - Herpes simplex virus type 1 (HSV-1) uracil-DNA glycosylase: functional expression
      in Escherichia coli, biochemical characterization, and selective inhibition by 6
      (p-n-octylanilino)uracil.
AB  - The Herpes simplex virus type 1 (HSV-1) uracil-DNA glycosylase (UDG) is encoded
      by the UL2 gene. The translation from the first putative start codon of UL2
      predicts a polypeptide of 334 residues, while the translation from the second
      start codon predicts a polypeptide of 244 residues. We have cloned and expressed
      the two forms of UDG, by means of the prokaryotic expression vector pMAL-c2, and
      both of them were enzymatically active. Furthermore, the enzymatic properties of
      the recombinant UDGs and of the enzyme purified from HSV-1-infected cells were
      similar. The two UDG polypeptides have molecular weights of 27 and 37 kDa,
      respectively. The 37-kDa form of recombinant UDG is consistent with the reported
      molecular mass of 37 kDa for the enzyme purified from HSV-1-infected cells. Both
      recombinant UDGs were as sensitive as UDG purified from HSV-1-infected cells to 6
      (p-n-octylanilino)uracil, the most potent of a series of uracil analogs that
      inhibit the viral enzyme.

PMID- 7645227
TI  - Virologic and serologic characteristics of a natural chimpanzee lentivirus
      infection.
AB  - This study set out to characterize the unique features of natural lentivirus
      infection in chimpanzees over time. The virologic and serologic characteristics
      of this infection were followed longitudinally in a naturally infected chimpanzee
      together with a small cohort of experimentally HIV-1-infected chimpanzees. The
      subsequent isolates from the naturally infected chimpanzee were all non-syncytium
      forming (NSI) versus syncytium forming in the experimentally infected animals. In
      contrast to HIV-1-infected chimpanzees virus load was higher and plasma viremia
      occurred but in a cyclic pattern. Serologic follow-up suggested the development
      of neutralizing antibodies with subsequent escape of new isolates. Interestingly,
      the sequence of the principal neutralizing (V3 loop) domain (of HIV-1) remained
      constant over time. Antibodies to peptides from the V3 loop were type specific.
      The occurrence of persistent, fluctuating plasma viremia and NSI-type virus
      variants of this natural lentivirus infection are unique characteristics not
      previously reported in experimentally infected chimpanzees.

PMID- 7645228
TI  - Identification of two human sequence-specific DNA-binding proteins which interact
      with the direct repeats in the squirrel monkey retrovirus long terminal repeat.
AB  - Squirrel monkey retrovirus (SMRV) is a xenotropic endogenous virus of the
      squirrel monkey. The long terminal repeat of the SMRV contains four direct
      repeats (43 or 42 bp) with different degrees of perfection in the U3 region.
      Herein, we found two human nuclear proteins (SMBP1 and SMBP2) which bind
      specifically to the direct repeats with different affinities. The binding
      proteins recognize overlapped sequences in the 5' region of the repeats. SMBP1
      and 2 are monomeric proteins of 35 and 17 kDa, respectively.

PMID- 7645229
TI  - Differentiation between minus- and plus-strand synthesis: polymerase activity of
      dsRNA bacteriophage phi 6 in an in vitro packaging and replication system.
AB  - Empty procapsids of the segmented dsRNA virus phi 6, produced in Escherichia coli
      from a cloned L genome segment, package plus-strand phi 6 ssRNA genomic segments,
      synthesize minus strands, and transcribe the newly formed dsRNA templates.
      Procapsids can be restricted to minus-strand synthesis by high concentrations of
      CaCl2 or low concentrations of nucleotides, enabling us to separate the viral
      minus-strand (replication) and plus-strand (transcription) RNA-dependent RNA
      polymerase activities in vitro. Reaction conditions for minus-strand synthesis
      were optimized. Plus-strand synthesis by procapsids could be activated by binding
      of purine nucleoside triphosphates to a low-affinity NTP-binding site. The second
      5'-terminal nucleotide of the phi 6 plus-sense ssRNA L genomic segment is
      important for determining the level of transcription of that segment and the
      generation of infectious procapsids.

PMID- 7645230
TI  - The effect of defective interfering RNAs on the accumulation of tomato bushy
      stunt virus proteins and implications for disease attenuation.
AB  - Tombusviruses, of which tomato bushy stunt virus (TBSV) is the type member,
      spontaneously generate defective interfering RNAs (DIs) that are known to
      interfere with viral accumulation and symptom development. We show that co
      infection with TBSV and DIs causes a dramatic reduction in accumulation of TBSV
      subgenomic RNAs and corresponding TBSV proteins with a less dramatic reduced
      accumulation of the genomic RNA and the replicase proteins. Associated with this
      differentially regulated suppression was a greatly reduced expression of both the
      p19 protein, which is responsible for severe symptoms, and the p22 protein, which
      is associated with cell-to-cell movement of the virus. Therefore, the results
      suggest that the protective effect of DIs may be due to selective inhibition of
      p19 and p22 expression in addition to reduced replication of genomic RNA.

PMID- 7645231
TI  - Specific single-stranded breaks in mature bacteriophage T7 DNA.
AB  - Both rate zonal centrifugation and gel electrophoresis have revealed that the
      mature double-stranded DNA of bacteriophage T5 has single-stranded breaks (nicks)
      at specific sites. Neither of these procedures has previously revealed site
      specific nicks in the double-stranded DNA of other bacteriophages, including T7.
      In the present study, denaturing gel electrophoresis, followed by specific DNA
      detection, reveals that a small fraction of mature T7 DNA molecules, like most T5
      DNA molecules, has site-specific nicks. The procedure of specific detection is to
      probe with an oligonucleotide specific for one of the ends of T7 DNA. If position
      0.0 is the left genetic end and position 100.0 is the right genetic end of T7
      DNA, the nicks on the 5' left-oriented strand are at 11.3, 12.4, 65.7, 79.2, and
      86.0; the nicks on the 5' right-oriented strand are at 23.3 and 26.5 (+/- 0.5).
      The positions of the three rightmost nicks are indistinguishable from those of
      double-stranded breaks that produce previously demonstrated shorter than mature
      length DNAs packaged in vivo. We propose that the T7 nicks are produced by
      premature activity of the T7 terminase during DNA packaging.

PMID- 7645232
TI  - A subgenomic RNA associated with cherry leafroll virus infections.
AB  - Cherry leafroll nepovirus (CLRV) genomic RNA 1 (8 kb) and genomic RNA 2 (7 kb)
      have 3' polyadenylate tracts and, extending 5' from the polyadenylate, nearly
      identical sequences of 1.6 kb termed the 3' common region. We observed RNAs 1 and
      2 and a third RNA of 1.5 kb in nucleic acid extracts of CLRV-infected Nicotiana
      tabacum suspension cell protoplasts and Chenopodium quinoa plants, using a
      hybridization probe complementary to 1 kb of the 3' common region. The third RNA
      was partially purified by preparative gel electrophoresis and chromatography on
      an oligodeoxythymidylate column. Analyses of transcripts primed by a
      complementary oligodeoxyribonucleotide and of cDNA clones revealed that the third
      RNA corresponds to the 3' 1500 nucleotide residues of RNA 1. Hence we designate
      the newly characterized RNA as RNA 1A. RNA 1A was not detected as encapsidated
      RNA in extracts of either protoplasts or C. quinoa plants. The amount of
      accumulated RNA 1A declined between 24 and 48 hr after inoculation of protoplasts
      with CLRV virions, although CLRV RNAs 1 and 2 continued to accumulate. Other
      results were not consistent with cleaved RNA 1 being the origin of RNA 1A. RNA 1A
      has the properties of a subgenomic RNA, presumably synthesized from negative
      sense RNA 1 as template.

PMID- 7645233
TI  - Poly(A) addition site mapping and polyadenylation signal analysis in a plant
      circovirus replication-related gene.
AB  - The transcripts of a genomic component of coconut foliar decay virus (CFDV), a
      plant circovirus with a single-stranded DNA genome, were characterized by
      sequencing the 3' termini of the respective cDNA clones. It was shown that
      transcription of the putative replication-related gene terminated at one major
      site (six bases downstream of the termination codon) in electroporated barley
      mesophyll protoplasts and that the resulting transcripts were polyadenylated. A
      deletion downstream of the AATAAA sequence including the poly(A) addition site
      did not inhibit polyadenylation signal activity but altered the distance between
      the polyadenylation signal and the polyadenylation site. However, deletion of the
      sequences upstream of the AATAAA stretch resulted in inhibition of the
      polyadenylation in this region. These observations and the finding of a silent
      CFDV AATAAA sequence downstream of the active poly(A) signal confirm the role of
      the upstream elements in processing of RNA transcripts in plants.

PMID- 7645234
TI  - Topography of variola smallpox virus inverted terminal repeats.
AB  - We examined the nucleotide sequences of the inverted terminal repeat (ITR)
      regions adjacent to the covalently closed hairpin end sequences of three variola
      major and four minor strains from smallpox outbreaks in Europe, Asia, Africa, and
      South America. The ITR regions ranged in size from 581 to 1051 base pairs (bp)
      and contained no apparent open reading frames. Two nonrepetitive sequence
      elements, NR1 and NR2, were conserved and resembled nonrepetitive elements in the
      ITRs of other orthopoxviruses. Depending on strain, the terminally positioned NR1
      and the more internal NR2 flanked a direct repeat region containing from none to
      four copies of a 69-bp sequence and one copy of a 54-bp related sequence partial
      repeat. A distinctive pattern of ITR topography of NR1 and NR2 flanking a single
      copy of the 69-bp unit characterized each of three examined alastrim variola
      minor strains. A nonalastrim African minor strain from the last natural case of
      smallpox in Somalia in 1977 showed the largest ITR region of the examined viruses
      because of a second direct repeat cluster following NR2.

PMID- 7645235
TI  - Biological significance of the seven amino-terminal basic residues of brome
      mosaic virus coat protein.
AB  - Inoculation of six brome mosaic virus (BMV) RNA3 transcripts with defined
      deletions in the coat protein (CP) gene to three Chenopodium spp demonstrated
      that synthesis of a functional, encapsidation-competent CP is required for the
      induction of local lesions. The BMV CP open reading frame contains two in-frame
      AUG codons separated by seven amino acids, resulting in the synthesis of two CPs
      (CP1 and CP2). To elucidate the biological significance of the N-terminal basic
      region of BMV CP, RNA3 variants capable of producing either CP1 or CP2 but not
      both were constructed. Infection phenotypes elicited on three Chenopodium spp by
      each RNA3 variant revealed that amino-terminal residues 1 to 7 are required to
      establish chlorotic local lesions and systemic infection in Chenopodium quinoa.
      Deletion of this region has no effect on infection in barley plants but resulted
      in the induction of the hypersensitive response on the inoculated leaves of C.
      quinoa and blocked systemic spread. Analysis of seven additional RNA3 variant
      transcripts, each having a six-base deletion (two amino acids) in the sequence
      encoding the N-terminal seven residues, indicated that variants that share a
      common deletion of positively charged lysine rendered the CP encapsidation
      incompetent and failed to establish infection. Taken together, these results
      suggest that residues 1 to 7 of the BMV CP play an important role in virus-host
      interactions and contribute differently to the virulence phenotype in different
      host plants.

PMID- 7645236
TI  - A myristylated membrane protein encoded by the vaccinia virus L1R open reading
      frame is the target of potent neutralizing monoclonal antibodies.
AB  - We identified a protein component of the intracellular mature vaccinia virion
      membrane that is a target of a potent neutralizing monoclonal antibody, 7D11,
      obtained from Alan L Schmaljohn. By immunofluorescent and electron microscopic
      analysis, MAb 7D11 was found to stain intracytoplasmic viral factories, virion
      membranes in cell sections, and the surface of negatively stained preparations of
      purified virions. The MAb 7D11 antigen, which is synthesized at late times in
      infection, has apparent molecular masses of 25 and 29 kDa under nonreducing and
      reducing conditions, respectively. The membrane antigen was most efficiently
      extracted from virions by NP40 detergent in combination with a reducing agent; in
      addition, the protein partitioned exclusively into the detergent phase when
      extracted with Triton X-114. Although the N-terminus of the immunoaffinity
      purified protein was blocked, sequence analysis of trypic peptides revealed that
      the MAb 7D11 antigen was identical to the myristylated protein encoded by the L1R
      open reading frame previously described by C.A. Franke, E.M. Wilson, and D.E.
      Hruby (1990, J. Virol. 64, 5988-5996). Validation of this genetic assignment was
      provided by the ability of MAb 7D11 to immunoprecipitate a [3H]myristic acid
      labeled product of the expected molecular weight from infected cells. In
      addition, we discovered that the previously described neutralizing monoclonal
      antibody 2D5 (Y. Ichihashi, T. Takahashi, and M. Oie, 1994, Virology 202, 834
      843) also recognizes the L1R protein.

PMID- 7645237
TI  - Restoration of the Epstein-Barr virus ZEBRA protein's capacity to disrupt latency
      by the addition of heterologous activation regions.
AB  - The ZEBRA protein has a unique biological function among herpesviral proteins. It
      is responsible for the disruption of Epstein-Barr virus (EBV) latency and the
      induction of the lytic cycle. ZEBRA is a bZIP transcriptional activator which
      binds as a dimer to 7-bp response elements within EBV promoters and is directly
      involved in the stimulation of virus replication at the EBV lytic origin. We have
      employed the ZEBRA/EBV biological system to test whether a heterologous
      activation domain can substitute for another activation domain (the ZEBRA
      domain). The ZEBRA activation region was replaced with the potent acid activation
      region from the herpes simplex virus VP16 protein or with the activation region
      of the EBV R protein. Both chimeras were found to transactivate model and native
      promoters at equivalent or better levels than ZEBRA itself. Activation was not
      target- or cell-type dependent, nor was it dependent on the presence of virus.
      These activation domains restored ZEBRA's ability to induce early antigen and to
      stimulate origin replication to levels that were equal to or greater than those
      of wild type. These studies suggest that the specificities of some of the known
      biological functions of ZEBRA are not dependent upon the nature of the activation
      domain present within ZEBRA.

PMID- 7645238
TI  - Mutational analysis of vaccinia DNA ligase defines residues essential for
      covalent catalysis.
AB  - DNA ligation entails AMP transfer from ATP to the 5' end of DNA to form a DNA
      adenylate structure, A(5')pp(5')N. A similar reaction involving GMP transfer
      occurs during 5' capping of eukaryotic mRNA. In both cases, nucleotidyl transfer
      occurs through a covalent lysyl-NMP intermediate. There is local sequence
      conservation among ligases and capping enzymes in the vicinity of the active site
      lysine (KxDG) and at three other collinear motifs. The role of these motifs in
      DNA ligation was tested by mutating individual conserved residues in the vaccinia
      virus DNA ligase. Wild-type and mutated versions of vaccinia ligase were
      expressed in bacteria as His-tagged fusion proteins and purified by Ni-affinity
      and phosphocellulose chromatography steps. We found that Ala substitution for Lys
      231 (the presumptive active site) abrogated enzyme-adenylate formation and DNA
      ligation activities. Ala mutations at conserved residues Glu-283, Glu-377, and
      Lys-397 also resulted in loss of ligation activity, which correlated with a
      defect in ligase-AMP formation. These results are concordant with mutational
      studies of yeast RNA capping enzyme and suggest a common structural basis for
      covalent nucleotidyl transfer.

PMID- 7645239
TI  - Expression of the mouse mammary tumor virus long terminal repeat open reading
      frame promotes tumorigenic potential of hyperplastic mouse mammary epithelial
      cells.
AB  - The retrovirus mouse mammary tumor virus (MMTV) 3' long terminal repeat (LTR)
      contains an open reading frame (ORF) for a 36-kDa protein and encodes a
      superantigen activity [pORF(sag)]. We have tested the potential oncogenic
      activity of pORF(sag) in two immortalized mouse mammary epithelial cells. We
      subcloned MMTV LTR ORF DNA into the pRc/CMV mammalian expression vector in order
      to place LTR ORF transcription under the control of the constitutive CMV
      promoter. Mouse mammary epithelial cell lines TM3 and FSK7e4 were transfected and
      G418-resistant cell clones were isolated. Reverse transcription-polymerase chain
      reaction and Northern blot analyses revealed modest overexpression of LTR RNA in
      several transfected cell clones of each line. Individual cell clones were
      transplanted into cleared mammary gland fat pads of syngeneic BALB/c mice. The
      parental cell lines and FSK7e4-derived clones did not form tumors, whereas ORF
      transfected clones derived from the TM3 cells formed tumors within 8 weeks in
      100% of transplanted fat pads in multiple experiments. The tumor cells expressed
      exogenous LTR ORF RNA and were proven to be derivatives of TM3 cells based on a
      marker p53 mutation. Immunohistochemistry using a polyclonal antiserum raised
      against pORF(sag) expressed in insect cells revealed a cytoplasmic reaction in
      TM3-CMV-LTR tumor cells; a much weaker cytoplasmic reaction was detected in the
      transfected tissue culture cells. These observations suggest that MMTV pORF(sag)
      may act as an oncogene in certain mouse mammary epithelial cells and raise the
      possibility that pORF(sag) may have a role in mammary tumorigenesis. As the
      parental FSK7 cell line has produced only ductal outgrowths upon transplantation
      in vivo and the TM3 cell line produces a nontumorigenic hyperplasia, the results
      suggest further that pORF(sag) may influence the latter stages of mammary
      tumorigenesis, namely, the preneoplastic to neoplastic transformation.

PMID- 7645240
TI  - Treatment of experimental intracranial murine melanoma with a neuroattenuated
      herpes simplex virus 1 mutant.
AB  - Brain metastases occur commonly in the setting of a variety of human cancers. At
      present, such cases are invariably fatal and highlight a need for research on new
      therapies. We have developed a mouse brain tumor model utilizing the Harding
      Passey melanoma cell line injected intracranially into C57Bl/6 mice. Tumors
      develop in 100% of the mice and can be detected by magnetic resonance imaging as
      early as 5 days post cell injection. Death from tumor progression occurs between
      12 and 16 days post cell injection. Stereotactic injection of the neuroattenuated
      HSV-1 strain 1716 into brain tumors 5 or 10 days postinjection of the melanoma
      cells results in a statistically significant increase in the time to development
      of neurological symptoms and in complete tumor regression and the long-term
      survival of some treated animals. Moreover, viral titration studies and
      immunohistochemistry suggest that replication of this virus is restricted to
      tumor cells and does not occur in the surrounding brain tissue. These results
      suggest that HSV-1 mutant 1716 shows particular promise for use as a therapeutic
      agent for the treatment of brain tumors.

PMID- 7645241
TI  - A defined system for in vitro lambda DNA packaging.
AB  - We constructed a defined in vitro system for packaging lambda DNA which is
      composed of purified proheads, the noncapsid proteins terminase and gpFI, and the
      Escherichia coli DNA binding/bending protein IHF. The defined packaging system:
      (i) is free from endogenous ATP, DNAs, and DNases and (ii) packages 30% of the
      input mature lambda DNA efficiently. In this defined packaging system, IHF and
      gpFI make modest contributions to packaging efficiency. The defined packaging
      reactions showed that DNA packaging gave a linear response to the concentration
      of mature lambda DNA and terminase. DNA packaging showed a sigmoidal relationship
      with respect to the concentration of ATP and proheads.

PMID- 7645242
TI  - Microevolution of type 3 Sabin strain of poliovirus in cell cultures and its
      implications for oral poliovirus vaccine quality control.
AB  - Screening for sequence heterogeneities in Sabin Type 3 strains of attenuated
      poliovirus demonstrated mutations that consistently accumulate to significant
      levels following 10 passages in cultures of primary African green monkey kidney
      (AGMK) cells or continuous cultures of Vero cells. Fourteen newly identified
      mutations were quantified by mutant analysis by PCR and restriction enzyme
      cleavage in passages and in batches of commercial vaccines made in AGMK and Vero
      cells from the Sabin original (SO) seed virus and from a seed virus rederived by
      RNA plaque purification (RSO or "Pfizer" seed). Nine of the 14 mutations were
      reproducibly observed in more than one series of passages. Although 5 other
      mutations were observed in only one set of passages each, their content gradually
      increased to a high percentage, suggesting that all the mutations that we found
      accumulated consistently. SO-derived samples accumulated more mutations than did
      RSO-derived ones, and the number of mutations and the rates of their accumulation
      were higher in Vero than in AGMK cells. While the rates of accumulation of most
      mutations were higher when passaging was performed at 37 degrees, a U-->C
      transition at nucleotide 5832 occurred faster at 34 degrees, the temperature used
      for vaccine production. Analysis of Type 3 oral poliovirus vaccine (OPV)
      monopools made by six manufacturers found only 5 of these newly identified
      mutations in vaccine batches (nucleotides 3956, 4935, 5357, 5788, and 5832). Some
      of the mutations were found in trace amounts (less than 0.1%) while others were
      present at up to 1.8% levels. The pattern of these mutations was characteristic
      for the type of seed virus and the cell substrate but demonstrated no correlation
      with results of the monkey neurovirulence test. Therefore the only mutation
      occurring in Type 3 OPV which contributed to neurovirulence in monkeys was the
      previously described reversion at nucleotide 472. Quantitation of reversion at
      nucleotide 472 can be utilized for assessment of acceptability of vaccine lots,
      while other mutations can be used for monitoring the consistency of vaccine
      production.

PMID- 7645243
TI  - Domains of the BPV-1 E1 replication protein required for origin-specific DNA
      binding and interaction with the E2 transactivator.
AB  - The viral E1 and E2 proteins are required for replication of bovine
      papillomavirus type 1 DNA. Both proteins bind as a complex to the replication
      origin, which consists of an E1 binding site flanked on either side by E2 binding
      sites. The E1 protein has properties common to replication initiator proteins
      such as sequence-specific origin binding and DNA helicase activities. The E2
      protein is a transcriptional transactivator that forms a complex with the E1
      protein and enhances binding of E1 to the replication origin. We have mapped the
      regions of the E1 protein required for sequence-specific DNA binding, for
      cooperative binding with the E2 protein to the origin region, and for interaction
      with the E2 protein. These studies demonstrate that a region between amino acids
      162 and 378 of the E1 protein is important for origin-specific DNA binding. The C
      terminal half of the E1 protein is required in addition to the DNA binding domain
      (residues 162 to 605) for cooperative binding to the origin with the E2 protein.
      Binding studies confirmed that this region is also required for efficient complex
      formation with the E2 protein.

PMID- 7645244
TI  - Assay for movement of Lepidopteran transposon IFP2 in insect cells using a
      baculovirus genome as a target DNA.
AB  - Mutagenesis of baculoviruses by host mobile elements occurs spontaneously and
      frequently during propagation of the viruses in Lepidopteran cell cultures. Most
      of the transposons identified as insertions in baculovirus genomes are relatively
      small Class II elements that exhibit a remarkable specificity for TTAA target
      sites. We have developed a transposition assay to analyze the movement of these
      TTAA-specific Lepidopteran transposons using the baculovirus genome as a target
      and a lacZ gene under control of the polyhedrin gene promoter as a selective
      marker for the transposon. This assay provides the first demonstration that a
      Lepidopteran transposon is capable of transposing while carrying a marker gene in
      insect cells. The data generated from this assay provide strong evidence that
      IFP2 encodes a protein that facilitates its own movement. This element may be
      used in a manner analogous to the P-element to mobilize genes in at least some
      Lepidopteran insect cells. Transposon tagging within the baculovirus genome
      identified several known genes and two previously undescribed open reading frames
      as nonessential to in vitro replication of the virus.

PMID- 7645245
TI  - Effects of adoptive immune transfers on murine leukemia virus-infection of rats.
AB  - In a rat model, we have investigated the effects of adoptively transferred virus
      specific immune cells on an established retroviral infection of various organs.
      The experimental design required inoculation of neonatal Fisher rats with a
      molecular clone of Friend murine leukemia virus (F-MuLV; FB29) which resulted in
      virus-specific immunotolerance, while infection of adult rats lead to a virus
      specific humoral and cellular immune response. Adoptive transfer of virus
      specific immune cells from immunized to immunotolerant (i.e., neonatally
      inoculated) rats was performed at around 15 days postpartum, a time when
      retroviral titers had already reached high levels in serum, spleen, thymus, and
      central nervous system (CNS). Seven days post-transfer (dpt), virus titers began
      to decline by 3-5 logs first in sera and at around 11-15 dpt, in spleens and
      thymi. Approximately 19 days post-transfer viral titers increased again. In the
      CNS, viral titers appeared not to change after adoptive transfer, although we
      observed an influx of activated T-cells and natural killer cells (NK-cells), but
      not of B-cells, into the CNS as well as an upregulation of major
      histocompatibility complex class I and II molecules between 8 and 21 dpt on both
      microglia and other brain cells. From these data we conclude that MuLV-infected
      cells of lymphoid organs can be eliminated by an antiviral immune response. In
      the CNS, however, most virus-infected cells escaped an immunological attack in
      spite of the presence of T- and NK-cells and may thus function as a reservoir for
      MuLVs.

PMID- 7645246
TI  - Characterization of human papillomavirus type 16 E2 protein and subdomains
      expressed in insect cells.
AB  - The E2 open reading frame of human papillomavirus type 16 (HPV-16) encodes a DNA
      binding protein which modulates papillomavirus transcription and replication. To
      investigate the biological and biochemical properties of the HPV-16 E2 protein,
      we have constructed recombinant baculoviruses which express the full-length
      molecule and individual N- and C-terminal domains in Sf21 insect cells. In this
      system the full-length E2 protein was phosphorylated and targeted to the insect
      cell nucleus. A 93 amino acid C-terminal fragment encompassing the DNA binding
      and dimerization functions of E2 was also translocated to the nucleus but was not
      modified by phosphorylation. The E2 N-terminal protein accumulated in the insect
      cell cytoplasm but was not efficiently phosphorylated. The formation of
      heterodimers between full-length and N-terminally truncated E2 species was
      observed when Sf21 cells were co-infected with recombinant viruses and when
      homodimers were mixed in vitro, suggesting that the dimer interface is not
      sufficiently stable to prevent subunit exchange in vivo. Both homo- and
      heterodimeric E2 species were able to bind specifically and in any combination to
      tandem E2 binding sites from the HPV-16 regulatory region. Furthermore, the HPV
      16 E2 protein bound to DNA exhibited a distinct susceptibility profile to pronase
      digestion, potentially contrasting with that reported for BPV-1 E2. These
      observations suggest that significant structural and functional differences may
      exist between the BPV/HPV E2 proteins and have implications for understanding E2
      dependent regulation of transcription and replication.

PMID- 7645247
TI  - An RNA stem-loop structure involved in the packaging of bovine leukemia virus
      genomic RNA in vivo.
AB  - An RNA secondary structure of the bovine leukemia virus (BLV) 5'-terminal RNA
      sequence was constructed by computer-assisted RNA secondary structure analysis.
      Mutations were created in the noncoding region (NCR) of BLV, which contains a
      conserved consensus sequence, to disrupt predicted secondary structure of this
      region. After transfection of these constructs into FLK-BLV cells and analysis of
      viral particles a reduction in mutant RNA content was observed relative to that
      of unmutated vector RNA. The packaging efficiency of the mutant with a
      substitution in the consensus sequence was reduced threefold and that of the
      mutant with a deleted 5' NCR was reduced fivefold. We conclude that predicted RNA
      secondary structure and/or nucleotide sequence of the BLV noncoding region is
      essential for BLV RNA packaging in vivo.

PMID- 7645248
TI  - CTL escape viral variants. II. Biologic activity in vivo.
AB  - The proteins of lymphocytic choriomeningitis virus (LCMV) contain only three
      known peptide regions that are processed and then held in place by the MHC class
      I H-2b (Db) glycoprotein on the cell's surface for recognition by LCMV-specific
      Db-restricted cytotoxic T lymphocytes (CTL). These peptides are from the
      glycoprotein (GP), amino acids 33-41 KAVYNFATC (GP1) and 276-286 SGVENPGGYCL
      (GP2), and the nucleoprotein (NP), 396-404. We have used CTL clones that
      recognized only GP1, GP2, and NP to select viral variants that upon infecting
      cells bearing H-2b molecules escaped recognition by virus-specific CTL directed
      against the viral GP (GP1 + GP2) mutant, termed GPV, or the viral GP and NP (GP1
      + GP2 + NP) mutant, termed GPV+NPV. These CTL "escape" variants nevertheless
      elicited sufficient host-protective activity in vivo to abort acute infection and
      prevent the occurrence of persistent infection. This protection was CD8+
      lymphocyte mediated and associated with the generation of a novel (for H-2b mice)
      CTL response to the viral L protein. Hence CTL epitopes form a hierarchy, in
      which responses to "weak" epitopes are suppressed in the presence of "stronger"
      epitopes. Mutation in the strong epitopes may be of limited biological
      significance since the host can mount a protective response directed against the
      second level (weak) epitopes.

PMID- 7645249
TI  - Poliovirus protease 3C mediates cleavage of microtubule-associated protein 4.
AB  - Poliovirus infection results in a number of host cell changes, including specific
      alterations in cellular proteins. This study further characterizes the cleavage
      of a cytoskeletal protein, microtubule-associated protein 4 (MAP-4) and
      investigates the identity of the viral protease which mediates its cleavage. MAP
      4 cleavage by poliovirus was previously identified using a monoclonal antibody
      (M. Joachims and D. Etchison, 1992, J. Virol. 66, 5997-5804). In this study, MAP
      4 cleavage was found to occur in cells infected by only some picornaviruses,
      poliovirus and human rhinovirus 14. Infection by other types of viruses,
      vesicular stomatitis virus and adenovirus, or by other types of picornaviruses,
      encephalomyocarditis virus, did not result in MAP-4 cleavage. To determine the
      viral mediator of MAP-4 cleavage, the effects of purified poliovirus proteases on
      MAP-4 integrity were examined by immunoblot. When MAP-4 substrates were incubated
      with concentrations of poliovirus 2A that were more than sufficient to induce
      p220 cleavage, there was no effect on MAP-4. However, when MAP-4 substrates were
      incubated with purified 3C protease (3Cpro), cleavage products were detected that
      were identical in size to those generated in vivo in poliovirus-infected cells;
      the use of a mutant 3C protease did not result in MAP-4 cleavage. Cleavage of MAP
      4 was also demonstrated with purified 3CDpro, and the in vitro cleavage kinetics
      were examined. Indirect immunofluorescence revealed that MAP-4 cleavage also
      correlated with a marked "collapse" of microtubules during late infection,
      indicating a possible relationship between 3Cpro-mediated MAP-4 cleavage and
      changes in the microtubule system of infected cells.

PMID- 7645250
TI  - The effect of inhibitors on the growth of the entomopoxvirus from Amsacta moorei
      in Lymantria dispar (gypsy moth) cells.
AB  - Within the family of Poxviridae, the entomopoxviruses are the most distant
      relatives of the more well-known and intensively studied orthopoxviruses
      (vaccinia and variola). The growth of the entomopoxvirus from Amsacta moorei
      (AmEPV) has been characterized in cell culture and compared to that of vaccinia
      virus (VV), the prototypic orthopoxvirus. The overall characteristics of infected
      cell cultures were generally similar between the two viruses. One striking
      difference noted was the apparent absence of proteolytic processing of late AmEPV
      viral proteins, a hallmark of vertebrate poxvirus infections associated with
      viral morphogenesis. AmEPV, like VV, was found to be sensitive to all the
      inhibitors of viral infection tested including phosphonoacetic acid, 1-beta-D
      arabinofuranosylcytosine, and isatin-beta-thiosemicarbazone (IBT), a compound
      associated with the rather specific inhibition of vertebrate poxviruses. While
      both VV and AmEPV are inhibited by IBT, the inhibition of AmEPV, unlike that of
      VV, is not accompanied by either a breakdown of ribosomal RNA or a global
      inhibition of late viral protein synthesis. Instead, in the presence of IBT,
      AmEPV enveloped, immature virions form devoid of a well-differentiated core,
      which unlike mature virions fail to insert into occlusion bodies.

PMID- 7645251
TI  - Long-term production of rotavirus antibody and protection against reinfection
      following a single infection of neonatal mice with murine rotavirus.
AB  - It has been found that mice infected with murine rotavirus can be protected
      against subsequent murine rotavirus infection for up to 2 months. It was also
      reported that protection against rotavirus infection in adult mice correlated
      with serum and stool rotavirus IgA titers. The present study was conducted to
      determine the duration of rotavirus antibody production and protection against
      rotavirus infection in this mouse model and its possible correlation with
      rotavirus antibody titers. It was found that protection of mice against
      subsequent infection following a single oral immunization with the murine
      rotavirus strain EDIM was 100% effective for at least 14 months, most of the
      lifetime of a mouse. During this period, serum and stool rotavirus antibody
      titers which included serum IgA, IgG, and neutralizing antibody to EDIM, as well
      as stool IgA, remained elevated. Of particular note, stool rotavirus IgA titers
      gradually decreased to levels that were approximately 10% of their peak at 1
      month after infection but did not decrease further, while serum rotavirus IgG
      titers continuously increased during the 14 months of the study. Serum rotavirus
      IgA titers varied from month to month but overall remained relatively constant
      throughout the 14-month period. Thus, both serum and stool rotavirus antibody was
      retained at substantial levels long after a single rotavirus immunization in the
      absence of reexposure, and mice remained protected against reinfection.

PMID- 7645252
TI  - Herpesvirus of turkey recombinant viruses expressing infectious bursal disease
      virus (IBDV) VP2 immunogen induce protection against an IBDV virulent challenge
      in chickens.
AB  - Two recombinant herpesviruses of turkey (HVT) expressing the VP2 protein of
      infectious bursal disease virus (IBDV or Gumboro disease virus) have been
      constructed: vHVT001 and vHVT002. The VP2 open reading frame was inserted at the
      locus of the small subunit of ribonucleotide reductase gene (HSV-1 UL40 homolog)
      without any exogenous promoter in vHVT001 and at the locus of gl gene (HSV-1 US7
      homolog) under the control of the human cytomegalovirus immediate-early promoter
      in vHVT002. The isolation of these recombinant viruses indicated that the deleted
      genes were not required for replication of HVT in chicken embryo fibroblasts.
      Efficacy of these recombinant viruses against IBDV strain 52/70 and Marek's
      disease virus (MDV strain RB1B) virulent challenges was evaluated in chickens
      vaccinated at 1 day of age. In the IBDV challenge, a good protection against
      mortality and bursal gross lesion was observed in vHVT002-vaccinated chickens:
      100% with 10(5) PFU dose and 60% with 10(4) PFU dose; in contrast, only a weak
      level of protection was achieved after vaccination with vHVT001. Protection
      levels against MDV challenge obtained with vHVT001 and vHVT002 were low (around
      10%) compared to that induced by the parental HVT (84%). In spite of the low
      protection level against MDV, this is the first report which describes induction
      of full protection against IBDV with a single inoculation of a recombinant virus.

PMID- 7645253
TI  - The virion host shutoff protein of herpes simplex virus inhibits reporter gene
      expression in the absence of other viral gene products.
AB  - The virion host shutoff (vhs) function of herpes simplex virus induces
      degradation of host mRNAs at early times and rapid turnover of viral mRNAs
      throughout infection. Previous studies have shown that disruption of the UL41
      gene abrogates vhs activity, but have not determined whether the UL41 polypeptide
      is the direct inducer of mRNA degradation or whether it is the only virion
      component required for this activity. In this paper we report that transfection
      of cells with UL41 inhibits expression of a cotransfected CAT reporter gene and
      that the inhibition is not dependent upon other viral genes. Inhibition of CAT
      expression was due to UL41-dependent reduction of CAT mRNA levels. UL41 alleles
      encoding polypeptides that lacked vhs activity during virus infections exhibited
      a similar lack of activity in transfected cells. The results indicate that the
      UL41 polypeptide is the direct inducer of host mRNA degradation following virus
      infection and that it is the only virion component directly required for this
      activity. A 382-amino-acid nonsense polypeptide missing the last 107 residues of
      UL41 lacked inhibitory activity, but was packaged into virions, while a 343-amino
      acid nonsense polypeptide lacked both inhibitory activity and the ability to be
      packaged.

PMID- 7645254
TI  - Effect of non-H-2-linked genes on anti-virus immune responses and long-term
      survival in mice persistently infected with E-55+ murine leukemia virus.
AB  - We have previously demonstrated that BALB/c-H-2k (BALB.K) mice are susceptible to
      the development of thymic lymphoma induced by E-55+ murine leukemia virus (MuLV).
      In the present studies, C57BL/10-H-2k (B10.BR) mice were found to be resistant to
      E-55+ MuLV-induced lymphoma despite the fact that these mice become persistently
      infected. This resistance to lymphomagensis is mediated by the anti-virus immune
      response since immunosuppressed mice progress to develop disease. The protective
      immune response in B10.BR mice is bimodal with respect to time after virus
      infection. The early immune response results in a dramatic decrease in the number
      of virus-infected cells within 4-8 weeks after infection. This decrease in virus
      infected cells occurs in immunocompetent mice from strains that are either
      resistant (B10.BR) or susceptible (BALB.K) to E-55+ MuLV-induced disease.
      Subsequently, susceptible mice develop an increase in infected cells, whereas no
      increase in infected cells occurs in resistant mice despite the fact that they
      are persistently infected. This later phase of resistance in B10.BR appears to be
      mediated by T cells. Since B10.BR and BALB.K both express the H-2k haplotype,
      resistance appears to be mediated by a non-H-2-linked gene(s). (BALB.K x
      B10.BR)F1 mice are resistant to disease development, indicating resistance is a
      dominant trait.

PMID- 7645255
TI  - Analysis of the fine structure of the prohead binding domain of the packaging
      protein of bacteriophage T3 using a hexapeptide, an analog of a prohead binding
      site.
AB  - A large subunit of bacteriophage T3 packaging enzyme, a product of gene 19 (gp19,
      586 amino acid residues), binds a prohead prior to DNA translocation in DNA
      packaging. Its C-terminal region (571 to 576, Region I) is of crucial importance
      for prohead binding. To elucidate the functional role(s) of Region I in DNA
      packaging, a hexapeptide (6pT3) corresponding to the Region I sequence and its
      variants were synthesized and their effects on DNA packaging in a defined in
      vitro system were examined. 6pT3 did not inhibit gp19wt (wild type)-prohead
      binding but interfered with their functional interaction, resulting in inhibition
      of DNA packaging. The inhibitory effect of 6pT3 on gp19wt was reversible. The
      effect of 6pT3 was examined with gp19 delta C10, which was active in DNA
      packaging in spite of lacking the extreme C-terminal 10 amino acids (Region II).
      The inhibitory effect on gp19 delta C10 was more severe than that on gp19wt and
      was irreversible. From these results, we concluded that the prohead binding
      domain is composed of two subdomains: Region I is a "core" domain, and its
      binding to the prohead is crucial for DNA packaging, and Region II is an "anchor"
      domain stabilizing the binding by Region I.

PMID- 7645256
TI  - Immunodetection, expression strategy and complementation of turnip crinkle virus
      p28 and p88 replication components.
AB  - The plus-sense RNA genome of turnip crinkle virus (TCV) encodes at its 5' end a
      28-kDa protein of unspecified function. Readthrough suppression of the p28 stop
      codon allows for the production of an 88-kDa product which is required for genome
      replication. Immunological analysis of the expression of p28 and p88 demonstrated
      that: (i) the genome directs the synthesis of polypeptides of approximately 28
      and 88 kDa, (ii) the 88-kDa protein is immunologically related to p28, consistent
      with p88 being a readthrough product, and (iii) p28, but not p88, is detectable
      in vivo. An in vivo assay, in which readthrough is linked to the expression of a
      beta-glucuronidase reporter gene, showed that readthrough of the p28 amber stop
      codon occurs with an efficiency of approximately 1%. A similar efficiency of
      readthrough was observed when an altered context from the nonviable TCV mutant,
      mA2, containing a disrupted secondary structure (FfFa) spanning the p28
      termination codon, was tested. This result suggests that the defective phenotype
      of mA2 is likely not linked to an alteration in readthrough efficiency.
      Additional studies demonstrated that complementation occurs in coinoculations
      with two nonviable TCV mutants, RT and APA, which are unable to express either
      p28 or p88, respectively. This result verifies that p28 is essential for TCV
      genome replication and provides the first definitive evidence for the role of a
      5'-proximal open reading frame for any member of the family Tombusviridae.

PMID- 7645257
TI  - Secretion and antigenicity of hepatitis B virus small envelope proteins lacking
      cysteines in the major antigenic region.
AB  - Disulfide bonds are of crucial importance for the structure and antigenic
      properties of the hepatitis B virus (HBV) envelope. We have evaluated the role of
      the eight highly conserved cysteines of the major antigenic region for assembly,
      secretion, and antigenicity of the envelope proteins. Mutants carrying single or
      multiple substitutions of alanine for cysteine were analyzed using epitope
      tagging and transient expression in COS-7 cells. The only single cysteines found
      to be indispensable for efficient secretion were Cys-107 and Cys-138, but double
      mutation of Cys-137 and Cys-139 also created a block to secretion. Poorly
      secreted mutants formed aberrant oligomeric structures. The antigenicity of the
      secreted or intracellularly retained mutants was analyzed using a panel of six
      monoclonal antibodies recognizing group- and subtype-specific determinants. We
      demonstrate that Cys-107 is critical for the structure of the group determinant
      a, whereas Cys-147, previously implicated in intramolecular disulfide bonding, is
      dispensable. Mutant proteins lacking Cys-121 and -124, -137, -147, or -149 have
      grossly distorted structures of the y subtype determinant. Our data raise the
      possibility that HBV strains carrying cysteine mutations are nonreactive in
      hepatitis B surface antigen-specific immunoassays.

PMID- 7645258
TI  - The human immunodeficiency virus tat gene enhances replication of human
      herpesvirus-6.
AB  - Human herpesvirus-6 (HHV-6) can enhance the cytopathic effects of human
      immunodeficiency virus type 1 (HIV-1) in cells doubly infected by HIV-1 and HHV
      6. HHV-6 enhances transcription of the HIV-1 long terminal repeat, and several
      HHV-6 trans-activator genes have been identified. Since HIV-1 and HHV-6 have
      similar cellular tropism, and since HIV-1 trans-activates other herpesviruses, a
      reciprocal interaction between the two viruses is possible. Interactions between
      HIV-1 and HHV-6 were analyzed in human umbilical cord blood (CB) lymphocytes and
      in a T-cell line by transfection and infection experiments. CB cells dually
      infected with HIV-1 and HHV-6 showed an increase in HHV-6 infectious titer, an
      increase in HHV-6-specific immediate early RNA, and an increase in HHV-6 protein
      synthesis. Similarly, T-lymphocyte cells transfected with the entire HIV-1
      proviral genome displayed an increase in HHV-6. When T-cells were transfected
      with a plasmid containing the HIV-1 tat gene under control of the simian virus
      (SV40) promoter and infected with HHV-6, higher levels of HHV-6 proteins and
      infectious virus were detected. Therefore, the presence of HIV-1 gene products,
      such as tat, can lead to an activation of HHV-6 expression. Since HHV-6 is
      cytopathic, its activation by HIV-1 may accelerate the depletion of CD4+ T-cells
      in infected individuals.

PMID- 7645260
TI  - Inhibition of phage phi 29 assembly by antisense oligonucleotides targeting viral
      pRNA essential for DNA packaging.
AB  - A sensitive and efficient system for the functional assay of antisense
      oligonucleotides (oligos) was developed based on an in vitro viral assembly
      system. A 120-base RNA (pRNA), which indispensably participates in bacteriophage
      phi 29 DNA packaging, was the target for antisense action. Antisense oligos bound
      to pRNA, as revealed by a slower electrophoretic mobility of pRNA/oligo complexes
      in comparison with native pRNA. Infectious viruses were assembled in vitro with
      synthetic pRNA and DNA, as well as with viral proteins produced from cloned
      genes. Up to 10(7) plaque-forming units per milliliter were obtained in the
      absence of antisense oligos, while as few as zero plaques were detected in the
      presence of certain antisense oligos. A 1-base mismatch greatly influenced the
      inhibitory effect of the antisense oligos, but this 1-based mismatch was not
      important when the mismatch was placed at the end of the oligo. Five oligos did
      not bind pRNA or inhibit the assembly of the virion, suggesting that the RNA
      sequences complementary to these oligos are nonessential or buried internally in
      the RNA. Viral assembly was strongly inhibited by antisense oligos P15 and P10,
      targeting either the 5'- or the 3'-end of the pRNA, respectively. Viral assembly
      was also strongly inhibited by oligo P6, targeting an internal region, residues
      75-91, of pRNA. Oligo P6 inhibited DNA packaging activity by blocking the binding
      of pRNA to the procapsid, while P10 and P15 inhibited DNA packaging activity but
      did not block the binding of pRNA to the procapsid, suggesting that in addition
      to the reported internal domain for procapsid binding, pRNA contains another
      domain at the paired 5'/3'-ends with a yet to be defined role in DNA
      translocation.

PMID- 7645259
TI  - Human parainfluenza virus type 3 phosphoprotein: identification of serine 333 as
      the major site for PKC zeta phosphorylation.
AB  - The human parainfluenza virus type 3 P protein is an RNA polymerase subunit
      involved in both transcription and replication during the life cycle of the
      virus. Our laboratory has recently shown that the P protein is phosphorylated
      both in vitro and in vivo by the cellular protein kinase C (PKC) isoform zeta and
      that this phosphorylation is essential for viral replication. To identify the
      site(s) of phosphorylation, we have used CNBr cleavage, phosphoamino acid
      analysis, and two-dimensional tryptic peptide mapping of the in vitro and in vivo
      phosphorylated P protein. We demonstrate that when bacterially expressed
      unphosphorylated P is labeled in vitro with either commercial PKC or purified
      recombinant PKC zeta P protein has one major phosphorylation site. By site
      directed mutagenesis of PKC consensus sites in the P protein, the primary
      phosphorylation site is found to be Ser 333. The same site appeared to be
      modified when viral P protein was phosphorylated in vitro by the PKC packaged
      within the virion and in the P protein of progeny virion labeled in vivo.

PMID- 7645261
TI  - Alternative amino acids at a single site in the Sendai virus L protein produce
      multiple defects in RNA synthesis in vitro.
AB  - Our long-term goal is to define the catalytic domains of the L protein subunit of
      the Sendai virus RNA polymerase. An aberrant polyadenylation phenotype in the
      vesicular stomatitis virus tsG16 L protein mutant has recently been identified as
      a phenylalanine to serine change at amino acid 1488 (Hunt and Hutchinson,
      Virology 193, 786-793, 1993). To test if functional domains are conserved in the
      L proteins of negative-strand RNA viruses, we attempted to create a similar
      polyadenylation defect in the Sendai virus L protein. Nine different amino acid
      substitutions at the analogous site in the Sendai L protein (cysteine at amino
      acid 1571) were constructed by site-directed mutagenesis of the gene. Each mutant
      L protein was synthesized and bound to the Sendai P protein to form the P-L
      polymerase complex. While none of these L mutants exhibited a change in
      polyadenylation, the single amino acid changes yielded a variety of activities in
      vitro. Mutants containing valine, leucine, or phenylalanine at amino acid 1571,
      amino acids found naturally in the L proteins of other paramyxoviruses, yielded
      polymerases that had biological activity equal to or better than the wild-type
      (WT) polymerase. Serine or threonine substitutions in the L protein at this
      position also resulted in polymerases with nearly WT synthetic activity. In
      contrast, a glycine substitution significantly decreased overall polymerase
      activity, whereas a tyrosine substitution gave decreased transcription, but
      virtually no DI genome replication in vitro. The tyrosine-substituted polymerase
      may be unable to carry out the packaging step of replication, since DI leader RNA
      synthesis was normal in this mutant. Mutant L proteins with basic arginine or
      histidine substitutions were inactive in all viral RNA synthesis in vitro,
      although the polymerase complexes could bind the nucleocapsid template.

PMID- 7645262
TI  - Abundance of an endogenous retroviral envelope protein in placental trophoblasts
      suggests a biological function.
AB  - To investigate the hypothesis that the human endogenous sequence ERV-3 has a
      function, we have cloned and expressed the transmembrane region of its envelope
      gene and raised specific antibodies to the fusion protein and to a synthetic
      peptide. These antibodies reacted with a 65-kDa polypeptide which constituted
      approximately 0.1% of the cellular protein in syncytiotrophoblasts in placenta.
      The evolutionary conservation and abundant expression of this endogenous
      retroviral protein in a specific cell type support the concept of a biological
      function. The similarity of a domain of ERV-3 env to putative immunosuppressive
      p15E sequences suggests that ERV-3 might form part of the placental
      immunosuppressive barrier between mother and foetus.

PMID- 7645263
TI  - Functional analysis of EA-D of Epstein-Barr virus.
AB  - Different mutations were generated in the diffused-form early antigen (EA-D) of
      Epstein-Barr virus (EBV) for study of the effects of these mutations in DNA
      binding, stimulating the activity of EBV-specific DNA polymerase (EBV-DP), and
      binding to monoclonal antibody R3. Results revealed that the N-terminal 303 amino
      acids were essential for DNA binding and were sufficient for the enhancement of
      the activity of EBV-specific DNA polymerase. Deletion study also showed that the
      region recognized by the R3 monoclonal antibody was located between aa 315 and aa
      377. Our results failed to demonstrate the binding between EA-D and EBV-DP, using
      the proteins synthesized in vitro, suggesting that direct contact between the two
      proteins is not required for the EBV-DP activity in vitro. We have generated
      fusion between EA-D and DNA-binding domain of yeast GAL4 protein; however, this
      fusion protein was not able to transactivate the promoter containing UAS sequence
      in P3HR1 cells.

PMID- 7645264
TI  - Correlation of dynamic responses in the ON bipolar neuron and the b-wave of the
      electroretinogram.
AB  - 2-Amino-4-phosphonobutyrate (APB) is known to selectively suppress the light
      response of ON bipolar cells in the vertebrate retina, and reduce the b-wave of
      the electroretinogram (ERG) as a consequence. Using slow drug application, the
      progressive effect of APB was used to compare the relative response amplitudes of
      the b-wave and the ON bipolar cell. Simultaneous ERG recordings and ON bipolar
      intracellular recordings were performed in the amphibian retina. The results
      indicate that there is a strong positive correlation between these two waveforms.
      This supports the possibility that the b-wave of the ERG is the direct result of
      ON bipolar cell activity.

PMID- 7645265
TI  - Isolation and characteristics of a steady-state visually-evoked potential in
      humans related to the motion of a stimulus.
AB  - We have examined the visual potential evoked by two motion stimuli. In the first
      stimulus (termed coherent motion) a random-dot pattern oscillated between phases
      of coherent and incoherent ("snowstorm") motion, and in the second a random-dot
      pattern alternated in direction of motion (termed direction change). We found
      that the response to the coherent motion stimulus is low-pass with respect to
      speed, has low contrast sensitivity and increases steadily with the contrast of
      the stimuli. The direction change visually-evoked potential (VEP) is band-pass
      with respect to speed, has high contrast sensitivity but then saturates and even
      reduces as the stimulus contrast is raised above 0.1. The behaviour of the
      direction change VEP is similar in nature to results from psychophysical
      experiments of motion perception and to the known properties of directionally
      selective cells of the cortex. On the other hand the behaviour of the coherent
      motion VEP suggests this may not be mediated by a mechanism specific to motion.

PMID- 7645266
TI  - Apparent speed of sampled motion.
AB  - Perceived speed was measured for stimuli moving unidirectionally in apparent
      motion with different sampling steps. The stimuli were displayed at successive
      locations for very brief durations (on-time = 1 msec). The basic result is an
      elevation of apparent speed produced by increasing the sampling step. This speed
      up effect is maximal at low speeds (2 deg/sec), then progressively decreases with
      higher speeds until it disappears at medium velocities (8 deg/sec). In addition,
      the speed-up observed at low speeds declines when the ontime is gradually
      increased from 1 msec to larger values, the largest one corresponding to
      "staircase motion". These results are consistent with models assuming that speed
      encoding is based on an antagonistic comparison of the activity in two broadly
      tuned temporal filters (low-pass and band-pass). The high temporal frequencies
      introduced by motion-sampling would activate the band-pass filter relatively more
      and would thus produce an overestimation of apparent speed.

PMID- 7645267
TI  - Spectral efficiency measured by heterochromatic flicker photometry is similar in
      human infants and adults.
AB  - Spectral efficiency functions based on heterochromatic flicker photometry (HFP)
      were measured for three adults and 42 infants using a rapid visually-evoked
      potential (VEP) method. A 5 degrees-diameter, broadband standard (0.6 cd/m2) was
      presented in square-wave counterphase (15 Hz) with one of 13 monochromatic lights
      (420-660 nm; 20 nm steps). The intensity of the monochromatic light was
      continuously varied while extracting the phase-locked VEP amplitude of the
      fundamental component. HFP functions measured psychophysically by the method of
      adjustment were also obtained for the adults. Adult HFP functions from the two
      methods were found to be essentially the same. Both of these functions were
      compared to Vos'-modified 2 degrees V(lambda) function and the 10 degrees
      CIEV(lambda) function. The mean adult data were slightly better fit to the 2
      degrees V(lambda) function than to the 10 degrees CIEV(lambda) function, although
      there was an elevation in sensitivity at 420 and 440 nm. Infant HFP functions
      were similar to Vos' modified V(lambda) except for an elevation in efficiency at
      short wavelengths. The mean infant HFP function agreed better with the 10 degrees
      CIEV(lambda) function than Vos'-modified V(lambda) function, but infant
      sensitivity was elevated by 0.4 log units at 420 nm compared to the 10 degrees
      CIE observer. The elevation found at short wavelengths for both adults and
      infants is attributed to individual and age-related variation in the density of
      the ocular media, and to reduced macular pigment screening resulting from use of
      a 5 degrees field size.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7645268
TI  - On the time-course of inhibition in the stereoscopic perception of rows of dots.
AB  - Perception of depth difference between two dots is more difficult if additional
      dots intervene between them. By varying the onset asynchrony (SOA) between the
      endpoints and one or several intervening dots, we measured the time-course of the
      process that elevates stereoscopic thresholds. It turned out that adding the
      intervening dots under these conditions decreased performance to, and often
      below, the level that was achieved with a total presentation time corresponding
      to the SOA for intervening dots presented both binocularly and monocularly. This
      is an indication for an active inhibitory process.

PMID- 7645269
TI  - Attentional modulation of adaptation to two-component transparent motion.
AB  - We have studied the effects of voluntary attention on the induction of motion
      aftereffects (MAEs). While adapting, observers paid attention to one of two
      transparently displayed random dot patterns, moving concurrently in opposite
      directions. Selective attention was found to modulate the susceptibility to
      motion adaptation very substantially. To measure the strength of the induced MAEs
      we modulated the signal-to-noise ratio of a real motion signal in a random dot
      pattern that was used to balance the aftereffect. Results obtained for adapting
      to single motion vectors show that the MAE can be represented as a shift of the
      psychometric function for motion direction discrimination. Selective attention to
      the different components of transparent motion altered the susceptibility to
      adaptation. Shifting attention from one component to the other caused a large
      shift of the psychometric curves, about 70-75% of the shift measured for the
      separate components of the transparent adapting stimulus. We conclude that
      attention can differentiate between spatially superimposed motion vectors and
      that attention modulates the activity of motion mechanisms before or at the level
      where adaptation gives rise to MAEs. The results are discussed in light of the
      role of attention in visual perception and the physiological site for attentional
      modulation of MAEs.

PMID- 7645270
TI  - Assimilation: asymmetry between brightness and darkness?
AB  - A pincushion formed by four arcs on a gray background looks darker when the arcs
      are black, and lighter when the arcs are white. Yet, a matching-experiment shows
      that this difference is relative. Whereas the apparently darker pincushion
      requires a matching luminance that is lower than the background luminance (i.e.
      assimilation), the apparently lighter pincushion curiously is also matched to a
      darker-than-background value (i.e. simultaneous contrast). A change-over in
      direction of a higher luminance occurs only at the lowest contrast. The size of
      the decrement required for matching the brightness of the pincushions increases
      with increasing contrast of the inducing stimulus, as well as with viewing
      distance. Assimilation is found also in the domain of color, however, only when
      the luminance of the colored inducers is below that of the background. Analogous
      asymmetries in the perception of darkness and lightness are discussed.

PMID- 7645271
TI  - The perceived speed of second-order motion and its dependence on stimulus
      contrast.
AB  - Speed matches were obtained, using a spatial two-alternative forced-choice task,
      between a second-order motion stimulus and a first-order motion stimulus. The
      second-order motion stimulus was composed of contrast-modulated noise [produced
      by multiplying two-dimensional (2-d), static noise by a drifting, one-dimensional
      (1-d) sinusoid]. The first-order motion stimulus was composed of luminance
      modulated noise (produced by summing, rather than multiplying, 2-d noise and a
      drifting sine grafting). In Expt 1, the relationship between the perceived speed
      of first- and second-order motion was examined. The motion stimuli had the same
      spatial frequency (1 or 3 c/deg) and were equated for visibility by presenting
      them at the same multiple of direction-identification threshold. Over a range of
      physical speeds, the perceived speeds of the first-order and second-order motion
      stimuli were identical when their physical speeds were the same. In Expt 2, the
      effect of varying stimulus "contrast" (contrast modulation depth) on the
      perceived speed of second-order motion was examined. The contrast of the first
      order motion stimulus was fixed and speed matches were obtained for second-order
      motion stimuli at several contrast modulation depths. The motion stimuli had the
      same spatial (1 or 4 c/deg) and temporal (5 or 20 Hz) frequencies. It was found
      that the perceived speed of second-order motion was approximately linearly
      related to log modulation depth. In agreement with previous studies we also
      confirmed that the perceived speed of first-order motion is similarly dependent
      on stimulus contrast (luminance modulation depth).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7645272
TI  - The hierarchical nature of perceiving direction of motion in depth from optic
      flow.
AB  - Monocular adaptation to flow fields of optic expansion and contraction juxtaposed
      on either side of fixation influenced subsequently perceived rotation direction
      of a figure rotating in depth (kinetic depth effect) about its vertical axis with
      a normally ambiguous direction. This influence was shown to be asymmetric since
      adapting to optic expansion produced significantly more aftereffects of
      translation in depth than did adapting to perceived rotation in depth when
      viewing a neutral test stimulus. The results are evidence for a hierarchical
      processing model for the perception of motion in depth from optic flow.
      Serendipitously, we discovered a new aftereffect from viewing kinetic depth
      rotation with direction specified by proximity-luminance covariation (PLC). The
      results and other research are discussed in terms of neural network models with
      synergistic interactions between levels.

PMID- 7645273
TI  - Saccadic eye movements while reading music.
AB  - Subjects' eye movements were measured whilst they read and performed lines of
      music consisting of rhythmic information only, in conventional musical notation.
      The relationship between the spatial pattern of the notes displayed and of the
      fixations made in reading them is stochastic, and similar to that in ordinary
      reading, but with a tendency to fixate salient details of the notation such as
      notes and barlines rather than the spaces in between. Shorter notes are less
      likely to be fixated than longer ones, and this is determined by their
      performance length rather than their visual appearance. Despite the timing
      constraints imposed by the music, the time of execution of individual saccades
      appears to be entirely unrelated to the time of the execution of elements of the
      performance itself. However, as the tempo of performance of a given piece of
      music is increased, the average time between saccades decreases but their mean
      amplitude increases. These observations suggest a new model of the oculomotor and
      perceptual processes involved, in which an central, iconic representation of the
      fixated image is internally scanned and interpreted to a given criterion of
      accuracy, the scan ending when this criterion cannot be reached, and this end
      point determining the position of the next fixation. It is proposed that the
      fullness of the buffer between the perceptual and motor processes determines the
      strictness of the criterion which is adopted, and hence the amplitude and timing
      of the eye movements.

PMID- 7645274
TI  - "Express" smooth pursuit.
AB  - For the majority of human smooth pursuit eye movements made to a horizontal ramp
      target of unpredictable direction, the reciprocal of the latency appears to have
      a Gaussian distribution of the same general form as for saccades to step targets,
      but with smaller median. There are more latencies shorter than some 100 msec than
      would be expected from such a distribution: they form a distinct population
      ("express smooth pursuit responses") whose distribution is similar to that of
      express saccades. They still occur in the absence of a cue, when the target is
      unpredictable.

PMID- 7645275
TI  - Interaction of stereo and texture cues in the perception of three-dimensional
      steps.
AB  - A computational method for calibrating stereo using shape-from-texture is
      described together with five experiments that tested whether the human visual
      system implements the method. The experiments all tested the prediction that the
      perceived size of a step between two planar and slanted real surfaces should be
      affected by texture slant cues projected on to them that are inconsistent with
      the disparity cues. The predicted effect was observed but the results could be
      accounted for by a new phenomenon revealed in control conditions: the perceived
      size of a step between two slanted planes is in part determined by the size of
      the slants even when texture and stereo cues are held consistent. We conclude
      that the hypothesis that human stereo is calibrated by texture is not confirmed.

PMID- 7645276
TI  - Enhanced S cone syndrome: evidence for an abnormally large number of S cones.
AB  - The cellular basis of the hypersensitivity of the S (blue) cone system in
      patients with enhanced S cone syndrome was examined by analyzing ERGs from three
      patients. The patients had large alpha-waves in response to the blue and white
      flashes. These alpha-waves were shown to be driven nearly entirely by the S
      cones. Although these S cone alpha-waves were 4-6 times the size of the normal
      L/M cone alpha-wave, they are of the same form, and could be quantitatively
      described with the same model previously shown to fit cone alpha-waves. We
      propose that the retina of these patients has many more S cones than the normal
      retina and that these cones replace some of the normal L/M cones and many of the
      rods.

PMID- 7645277
TI  - Contrast sensitivity and coherent motion detection measured at photopic luminance
      levels in dyslexics and controls.
AB  - Development dyslexics perform differently from controls on a number of low level
      visual tasks. We carried out three experiments to explore some of these
      differences. Dyslexics have been found to have reduced luminance contrast
      sensitivity at mesopic luminance levels. We failed to replicate this finding at
      photopic luminance levels. We also compared the (photopic) coherent motion
      detection thresholds of groups of child and adult dyslexics with those of age
      matched controls. Dyslexics were significantly less sensitive to motion. The
      results are discussed in relation to a recent suggestion that developmental
      dyslexia may be associated with a magnocellular visual deficit.

PMID- 7645278
TI  - Visual acuity vs letter contrast sensitivity in retinitis pigmentosa.
AB  - This study examined the quantitative relationship between foveal visual acuity
      and contrast sensitivity for large-letter optotypes in a group of patients with
      retinitis pigmentosa (RP), in order to assess more completely the extent of
      foveal vision loss in this group of hereditary retinal dystrophies. High-contrast
      visual acuity and large-letter contrast sensitivity were measured with a computer
      based testing system and with commercially available letter charts (Lighthouse
      Distance Visual Acuity Test; Pelli-Robson Contrast Sensitivity Chart). Findings
      from 20 patients with typical RP or Usher syndrome were compared with those from
      15 age-similar control subjects with normal vision. On both the computer-based
      test and the chart tests, the patients with RP showed approximately equal
      reductions in visual acuity and large-letter contrast sensitivity. However,
      intersubject controls was greater for contrast sensitivity than for visual acuity
      on both test protocols. As a result, the patients with RP required a greater
      reduction in contrast sensitivity than in acuity to exceed the normal range,
      indicating that visual acuity was the more sensitive index of the loss of foveal
      visual function.

PMID- 7645279
TI  - [The significance of the experience in organizing medical support for the troops
      during the war years for the development of the modern military medical
      infrastructure].
AB  - In the present period when combat activities are being carried out at the
      territory of Russia, namely in Chechnya, it is very important to solve the
      problem of the improvement of the infrastructure of medical service as a basis of
      territorial system of medical support of troops. That's why we are looking at the
      experience of medical support of troops in the period of the Great Patriotic war
      in order to determine the basic characteristic features of military medical
      infrastructure (MMI) of that time. Using the experience of medical support in the
      period of the Great Patriotic war it is necessary to draw the main attention on
      studying the medico-geographical aspects of the Armed Forces deployment over the
      whole territory of the country, state of health service system (taking into
      account its reformation), influence of natural, socio-economic and ecological
      factors of different regions upon the health of servicemen, organization of
      medical support of troops, proliferation of infectious and parasitic diseases,
      local resources and availability of medication materials, medical supplies,
      equipment and technique, as well as other indices which must be taken into
      consideration in routine situations or during disaster relief. All this
      information is very valuable for the process of the formation of an adequate MMF
      in the zone of responsibility of medical support of troops.

PMID- 7645280
TI  - [The activities of the military medical academies during World War II].

PMID- 7645281
TI  - [The role of science in the development of military medicine during World War
      II].

PMID- 7645283
TI  - [The role of the Military Medical Museum in summarizing the experience of medical
      support for the troops in World War II].

PMID- 7645282
TI  - [The organization of the command of the rear hospital bases in the USSR during
      World War II].
AB  - In the result of studies of the concrete materials (archives, official,
      scientific and other historical data) about the work of hospital bases of the
      strategic rear (HBSR) on the territory of the Siberia region the author gives
      characteristic features of the commanding system of HBSR in 1941-1945, evaluating
      the positive experience of cooperation between the Popular Commissariat of Health
      of the USSR and the Main Military Sanitary Department of the Red Army, i.e. two
      main institutions which were conducting immediate direction over the activities
      of evacuation hospitals of the strategic rear of the country. In the author's
      opinion, these data could be used not only as historical materials. The article
      contains various considerations of the former commanding officers of the medical
      department of Siberian Military District, as well as the opinion of the Chief of
      the MMSD E. I. Smirnov about the system of subordination throughout the chain of
      command of evacuation hospitals of the strategic rear of the country.

PMID- 7645284
TI  - [Medical support for the landing in the Eltigen area in 1943].
AB  - The authors have used archive data to show the peculiarities of medical support
      of naval landing of troops at the region of Eltigen. The 279-th medical battalion
      immediately after landing was under constant fire from all sides, including the
      sea. Dugouts and caponiers were erected in mountains to deploy hospital
      facilities. In the conditions of severe blockade the medical battalion was
      occupied with admission of wounded, their surgical treatment and post-operational
      care in the conditions of almost complete lack of medications, dressing and
      sterile linen. Totally in the period from November 1 till December 6, 1943 in
      Eltigen area medical service have provided medical care to 1800 wounded and 140
      sick servicemen. An active surgical treatment was conducted in 1560 wounded
      (86.7%), 720 soldiers were evacuated and 500 returned to their ranks.

PMID- 7645285
TI  - [The aftermath of the fascist air attacks on military ambulance trains and mobile
      units].
AB  - The article summarizes the archive data concerning the results of the bombing
      attacks and machine-gun fire of fascist aviation against hospital trains and
      sanitary trains (HT & ST). During the war period 349 HT & ST have suffered air
      attacks (including 95 organic HT, 111 temporary HT, and 143 ST). In the result of
      these attacks the losses among the medical personnel of HT & ST were 1682 wounded
      and 833 killed. As for sick and wounded who were being evacuated by these HT & ST
      3040 of them were repeatedly wounded, 2017 were killed or burned by fire in
      railway medical carriages. These data testifies the flagrant transgression by
      fascists of international agreements on the neutrality of sanitary transport and
      its personnel.

PMID- 7645286
TI  - [The contribution of the medical service to victory in World War II].
AB  - The article analyses the work of the Soviet medicine in the years of the Great
      Patriotic war, and the contribution made by the Army and Navy Medical Service for
      the Victory. From the whole number of 14.5 million wounded more than 10.5 million
      were returned to their ranks, as for sick servicemen, more than 6.5 million from
      the whole number of 7.5 million were returned to their duties. Lethal cases among
      wounded were 5.3%, and among sick--3.7%. For example, the reduction of lethal
      cases per 0.1% signified to save life for 4-5 thousand wounded and sick. By the
      end of the war the lethality in penetrating cranium injuries has lowered 45.8%,
      in penetrating chest injuries with open pneumothorax--10%, without open
      pneumothorax--57%, in thoracoabdominal injuries--30%. Medical service had
      achieved a considerable reduction of invalidity among servicemen. In 1943 27
      evacuation hospitals were transformed in recovery surgery hospitals, as for
      patients of these hospitals, 8% of them were returned to their ranks in the
      active army, 36% were able to work accordingly to their professions, 19% have
      recovered wording capacity after receiving a new profession. The system of
      recovery treatment made it possible to return to labour hundred thousands of
      wounded and sick. Antiepidemic system of medical service had assured a reliable
      and opportune prevention of epidemic outbreaks of infections and parasitic
      diseases, interdicting its spreading from the front line to the rear, and from
      the rear areas to the active army. Many medical workers have perished providing
      health care to the wounded and sick soldiers. More than 5 thousand physicians,
      over 9 thousand low-grade medical workers, and 48 thousand aidmen and stretcher
      men were killed or lost in action. More than 125 medical workers were wounded.

PMID- 7645287
TI  - [The organization of the treatment of the wounded and sick prisoners of war in
      hospitals at the rear in the USSR during World War II].
AB  - The international humane principles were strictly observed by medical workers of
      our country in providing medical care to the wounded and sick PW during the Great
      Patriotic war. By February 1, 1945 from the whole number of 671340 beds which
      were deployed in the hospital system of the strategic rear, several hospitals
      with the total number of 47770 beds were used for providing medical care to the
      wounded and sick PW. These hospitals were capable to provide all type of
      secondary and tertiary care. Medical workers of these hospitals were also
      accomplishing the missions on sanitary-epidemiological welfare of PW. The
      detailed studies of the system of medical care in PW hospitals in the region of
      Middle Volga basin have prove this fact.

PMID- 7645288
TI  - [Landing forces (from the notes of a military physician)].

PMID- 7645289
TI  - [Iosif Fedorovich Zhordania (on the centenary of his birth)].

PMID- 7645290
TI  - [In single formation].

PMID- 7645291
TI  - [The treatment and rehabilitation of ENT patients during World War II].

PMID- 7645292
TI  - [The delivery of ophthalmological care in World War II].
AB  - The basic questions of organization of the military field ophthalmology were
      worked out by B. L. Poliak and tested on practice before the Great Patriotic war
      during Japanese conflict on the Khalka [correction of Khalkhin-Gol] River and in
      Soviet-Finnish war. Ophthalmological care during the Great Patriotic war had a
      number of innovations, such as stitching of fibrotic membrane, electromagnetic
      removal of foreign bodies, and application of complex treatment made it possible
      to lower the cases of preventive enucleation and reduce the time of plastic
      operations. In the result of these methods the blindness came to 3.9% (in US Army
      -5.1%).

PMID- 7645293
TI  - [The organization of psychoneurological care in 1941-1945].

PMID- 7645294
TI  - [Epidemic-control support for the combat operations of the Soviet troops in
      Afghanistan in light of the experience of World War II].
AB  - The article summarizes the experience of antiepidemic support of combat
      operations of the Soviet troops in Afghanistan. The basic antiepidemic principles
      which were worked out during the Great Patriotic war are still actual and must be
      used in organization of antiepidemic measures in local wars and military
      conflicts. The following aspects are of most practical significance in this
      matter: sanitary-epidemic reconnaissance, pre-operational readiness of troops,
      preventive measures to interdict the spreading of the infection to the cantonment
      areas when the units return from combat operations.

PMID- 7645295
TI  - [The characteristics of the epidemiology and prevention of transmissible
      infections during World War II].
AB  - During the war period the most proliferated transmissible infections were typhoid
      and bilious typhoid, malaria, and in certain areas--tularemia. The maximum
      typhoid morbidity was in 1942-1944 (annual increase in February-May, being March
      a peak point month). As for malaria, the most spreading period was in 1944. Its
      seasonal increase was in July-October (September-peak point). Besides common
      methods of struggle against transmissible infections a number of measures against
      carrying agents were used, but these didn't receive wide application because of
      lack of effective insecticides for inhalation of imago and grubs of mosquitos. At
      that time only the "K" preparation and its modifications were available. "DDT"
      had appeared only in 1944.

PMID- 7645296
TI  - [The use of the experience of hygienic support for the troops during World War II
      in the training process].
AB  - During the Great Patriotic war military medicine have succeeded not only in
      treatment of servicemen (72.3% of wounded and 90.6% of sick were returned to
      their duties), but also in preventing mass epidemic outbreaks of infectious
      diseases among Armed Forces personnel and civilian population. The experience of
      hygienic support of troops at the combat theater is used in the process of
      training during military hygiene studies. On the lectures and practical studies
      on this subject students learn the principles of hygienic support which were
      worked out by F. G. Krotkov--the former Senior Hygienist of the Red Army during
      the war period. Despite the hard military situation our country had succeeded in
      providing the Army with sufficient food supplies. A constant control was realized
      over the food ration. A special attention was drawn at laboratory control. The
      food ration had included 115 g of proteins, 80-90 g of ascorbic acid. Vitamin
      tinctures were widely used. As for water control the main attention was paid to
      interdiction of epidemic outbreaks.

PMID- 7645297
TI  - [A celebration in honor of World War II veterans by the Main Military Medical
      Directorate of the Ministry of Defense of the Russian Federation].

PMID- 7645298
TI  - Physicians' attitudes toward a new gynecological examination gown.
AB  - Gynecologists' attitudes toward an examination gown found in previous studies to
      reduce patients' distress during examination were investigated. Twenty-six
      gynecologists in four cities volunteered to use the new examination gown and
      complete a questionnaire evaluating the gown for adequacy of design and perceived
      patient comfort. Participants rated the gown positively overall. Favorability
      ratings were highly correlated with ratings of the structural adequacy of the
      gown for performing the breast, back, and pelvic exams. Favorability was also
      highly correlated with physicians' perceptions of the patients' comfort with the
      gown. The new gynecological examination gown is well accepted by gynecologists.
      It appears that gynecologists are open to changes in examination procedures that
      do not interfere with the exam and increase patient comfort. This new gown offers
      a strategy for decreasing patient distress during examination, which may reduce
      delay in seeking examinations.

PMID- 7645299
TI  - Women's roles and health: the mediating effect of perceived control.
AB  - Research concerning women's roles and health has revealed inconsistencies
      regarding the effects of work/family roles on women's health. Recent work in this
      area suggests that role characteristics or role quality may be more important in
      determining health than simple role occupancy. In addition, it has been suggested
      that role factors may affect health by increasing or decreasing one's perceptions
      of personal control over life. This study uses logistic regression techniques on
      data from the 1987 General Social Survey to explore the effects of roles and role
      quality on women's health, as well as the mediating effects of perceived control
      in the relationship between role factors and health. It is hypothesized that (1)
      role quality variables are better predictors of health than role occupancy, (2)
      the effects on health of roles, and role quality, are mediated by perceived
      control. In the role occupancy model, findings show that employment is the only
      role associated with health, and perceived control does modify this relationship
      slightly. Both high and low quality employment roles predict better health,
      whereas only high quality marital roles predict better health. While perceived
      control does mediate slightly the effects of job quality on health, the positive
      effects of marital status on health are suppressed slightly by perceived control.

PMID- 7645300
TI  - Directiveness in prenatal genetic counseling.

PMID- 7645301
TI  - Gender differences in fire fighter job stressors and symptoms of stress.
AB  - This study described gender differences in fire fighter appraisal of job
      stressors and symptoms of stress. A sample of 670 male and 41 female fire
      fighters responded to an anonymous mail survey consisting of three standardized
      and investigator-developed questionnaires. Male and female fire fighter
      respondents were more similar than different on both job stressor and symptoms of
      stress measures. Five job stressors were ranked the most "bothersome" by both
      males and females during the last 10 shifts worked. These were: sleep
      disturbance, wage/benefit concerns, job skill concerns, substandard equipment,
      and safety concerns. Of these five job stress factors, only one gender difference
      was noted. Female fire fighters reported significantly higher scores than males
      on job skill concerns. Job discrimination reported by female respondents was
      significantly higher than for males (t = 3.51, p < .0001) even though it was not
      ranked among the five most stressful factors. Partial correlations computed
      between job stressors and symptoms of stress, while controlling for the number of
      years as a fire fighter, were of moderately high magnitude for both genders and
      similar to simple correlations computed. These results suggest that the number of
      years of service did not account for gender differences reported.

PMID- 7645302
TI  - Three-dimensional models of human and other mammalian microsomal P450s
      constructed from an alignment with P450102 (P450bm3).
AB  - 1. A novel modelling alignment for P450s, utilizing NADPH-P450 reductase for
      electron transfer, is proposed on the basis of analysis of their amino acid
      sequences. 2. Information used to facilitate the alignment process includes: the
      recent X-ray crystal structure of P450102 (P450bm3), site-directed mutagenesis
      experiments, chemical modification of specific residues, and antibody recognition
      studies. 3. The alignment has been used to construct a number of microsomal P450s
      of relevance to xenobiotic and endogenous metabolism.

PMID- 7645303
TI  - Kinetics of ranitidine metabolism in dog and rat isolated hepatocytes.
AB  - 1. Freshly isolated hepatocytes from rat and dog have been evaluated as a model
      for the metabolism of ranitidine in vivo. 2. Isolated hepatocytes from the male
      and female dog and male Wistar and random hooded rat metabolized ranitidine to
      ranitidine N-oxide, ranitidine S-oxide, desmethylranitidine and two unidentified
      minor metabolites. The furoic acid metabolite of ranitidine, previously reported
      to be a minor metabolite in vivo in rat and dog, was not detected in hepatocytes
      from either species. 3. The kinetics for ranitidine metabolism in hepatocytes
      were monophasic for the formation of the three major metabolites in dog and
      Wistar rat and for N-demethylation of ranitidine in the random hooded rat, but
      biphasic in this latter strain for the N- and S-oxidation of ranitidine. 4.
      Ranitidine N-oxide was reduced to ranitidine by Wistar rat hepatocytes but not by
      hepatocytes from the random hooded rat or dog. Ranitidine S-oxide was metabolized
      by hepatocytes from both species to one of the unidentified metabolites but was
      not reduced to ranitidine in either species. Desmethylranitidine was not a
      substrate for metabolism in hepatocytes from either species. 5. The relative
      quantitative importance of ranitidine N-oxide, ranitidine S-oxide and
      desmethylranitidine produced by the hepatocytes was consistent with the profiles
      of these three metabolites in vivo in rat and dog. The results confirm the value
      of isolated hepatocytes as a predictive model for in vivo drug metabolism.

PMID- 7645304
TI  - Metabolism of thioridazine by microsomal monooxygenases: relative roles of P450
      and flavin-containing monooxygenase.
AB  - 1. The metabolism of thioridazine by the flavin-containing monooxygenase (FMO) of
      mouse liver and several P450 isozymes was examined using microsomes, purified
      FMO, and expressed P450 isozymes. Metabolites were identified by hplc. 2. Thermal
      inactivation and antibodies to NADPH P450 reductase were used to selectively
      inactivate FMO and P450 respectively. Inactivation of FMO by heat-treatment
      reduced the formation of thioridazine-N-oxide and northioridazine, whereas
      inactivation of P450 resulted in decreased amounts of thioridazine-2-sulphoxide,
      northioridazine, and thioridazine-5-sulphoxide. 3. Liver microsomes from mouse
      induced with phenobarbital, 3-methylcholanthrene, or acetone were compared with
      control microsomes. Phenobarbital induction resulted in increased formation of
      all metabolites except thioridazine-N-oxide, while retaining a general metabolic
      profile similar to that achieved with control microsomes. Neither 3
      methylcholanthrene nor acetone induction had any effect on the in vitro
      metabolism of thioridazine. 4. FMO purified from mouse liver produced
      thioridazine-N-oxide as the major metabolite. 5. Preliminary experiments with
      commercially prepared microsomes made from cells expressing recombinant human
      liver P450 2D6 and 3A4 suggested that thioridazine is metabolized by 2D6 but not
      3A4.

PMID- 7645305
TI  - Comparative induction of cytochrome P4504A in rat hepatocyte culture by the
      peroxisome proliferators, bifonazole and clofibrate.
AB  - 1. The influence of imidazole and triazole antifungal drugs on cytochrome P450
      levels in male Wistar primary rat hepatocyte culture for 70 h has been
      investigated and compared with clofibrate. 2. Bifonazole, clotrimazole,
      geniconazole clofibrate induced total P450 in hepatocytes, whereas itraconazole,
      miconazole and UK-47,265 did not. 3. When the CYP4A subfamily was examined, only
      bifonazole and clofibrate induced CYP4A as assessed by both Western blot analysis
      and the 11- and 12-hydroxylation of lauric acid. 4. By analysis of concentration
      response curves in hepatocyte culture, bifonazole was 160 and 40 times more
      potent than clofibrate for induction of the 11- and 12-hydroxylation of lauric
      acid respectively. 5. Taken collectively, our data have identified bifonazole as
      a relatively potent, non-carboxylate inducer of CYP4A and the mechanism of
      induction and specificity of this azole is discussed.

PMID- 7645307
TI  - Metabolism of aminopyrine and derivatives in man: in vivo study of monomorphic
      and polymorphic metabolic pathways.
AB  - 1. The main metabolic pathways involved in the biodisposition of aminopyrine have
      been monitored in vivo in 60 healthy volunteers by measuring the amount of parent
      drug and metabolites recovered in the urine 24 h after oral administration of 250
      mg aminopyrine. 2. The amount of metabolites in the 24-h urine was (mean +/- SD
      of 60 individuals): unchanged aminopyrine, 0.2 +/- 0.2 mg; methyl
      aminoantipyrine, 4.5 +/- 2.8 mg; formyl aminoantipyrine, 18.5 +/- 10.1 mg;
      aminoantipyrine, 9.2 +/- 6.6 mg; and acetyl aminoantipyrine, 31.8 +/- 21.1 mg. 3.
      Large interindividual differences (12-200-fold changes) are present in all the
      metabolic steps involved in aminopyrine biotransformation. These differences are
      not related to gender, intake of caffeine or alcohol, or known drug-metabolizing
      polymorphisms such as those involved in debrisoquine or mephenytoin metabolism.
      In contrast, smoking resulted in a decrease in the N(4)-demethylation ratio (p =
      0.011). 4. The interindividual differences followed an apparently normal
      distribution in the N(4)- and N(2)-dimethylation and formylation pathways (p >
      0.1). In contrast, acetylation follows a polymorphic distribution (p < 0.03),
      with an apparent antimode ratio close to 4. With the exception of the acetylation
      pathway, all of the metabolic ratios correlated between themselves (p < 0.001).

PMID- 7645306
TI  - Metabolism of gemcitabine in rat and dog.
AB  - 1. The metabolism of 14C-gemcitabine in the male rat has been studied after
      intravenous administration of a single dose (10 mg/kg) or five doses (1
      mg/kg/day) of 14C-gemcitabine. The metabolism in male dog has been studied after
      only single dosing. The effects of gemcitabine on hepatic drug-metabolizing
      enzymes in rat has also been studied. 2. The concentration of gemcitabine in the
      plasma was 11.84 micrograms/ml at 5 min, and then rapidly decreased after a
      single administration to rat. A deaminated uracil analogue of gemcitabine
      progressively increased with time. Gemcitabine and the uracil metabolite
      accounted for 80.0 and 11.8% of the radioactive dose in the 0-24-h urine samples
      respectively. Gemcitabine was the major component identified in lung, liver and
      kidney at 5 min after administration. 3. After repeated administration to rat,
      metabolites in the plasma and tissues were not remarkably different from those
      found after a single administration. 4. After a single administration to dog, the
      plasma concentration of gemcitabine was 12.39 micrograms/ml at 5 min. Gemcitabine
      and the uracil metabolite accounted for 8.3 and 71.8% of the dose in the 0-24-h
      urine samples respectively. 5. No differences were observed in enzymatic
      activities per whole liver between the gemcitabine-treated and control rat.

PMID- 7645308
TI  - Altered renovascular resistance after spontaneous recovery from hemolytic uremic
      syndrome.
AB  - Twenty-three patients were evaluated from 1-15 (mean 6) years after recovering
      from an episode of diarrhea-associated associated childhood hemolytic uremic
      syndrome (DA-HUS). All patients had received only conservative treatment; none
      had been given experimental, anti-coagulant, or immunological therapies. Follow
      up studies included morphologic and duplex Doppler sonograms. Doppler sonography
      was used to determine the resistive index, a measure of renovascular resistance.
      Histories and physical examinations revealed no abnormalities. Results of
      laboratory studies, which included calculated glomerular filtration rates, were
      all within normal limits, except for one patient with minor urinary
      abnormalities. Renal sonograms showed no significant abnormalities of kidney
      length or parenchymal appearance. However, Doppler sonographic examinations
      revealed that the DA-HUS patients demonstrated less of a decrease in renovascular
      resistance with age than did the control group (p < 0.0002). After recovery,
      patients treated exclusively with conservative management during an acute episode
      of DA-HUS appeared to have an excellent long-term prognosis. Comparison of our
      results with those from other studies in which investigational therapies have
      been used during the acute phase of DA-HUS suggests that latent toxicities which
      cause long term sequelae may not have been appreciated previously. The clinical
      significance of the altered renal vascular resistance remains to be delineated.

PMID- 7645309
TI  - How long can we live?
AB  - The continuing rapid age shift in recent years from predominately a younger to an
      older population in America and many other countries is a problem of great
      concern. Its socioeconomic implications for the distant future are quite
      unpredictable due to our inability to answer a few basic questions. How long will
      life expectancy continue to increase? What is the maximum possible length of
      life?

PMID- 7645310
TI  - Early psychiatry at Yale: Milton C. Winternitz and the founding of the Department
      of Psychiatry and Mental Hygiene.
AB  - Yale's current department of psychiatry was created by Dean Milton C. Winternitz
      in the 1920s as part of a broader effort to combine mental and physical
      components of medical care. This effort, which spurred the founding of Yale's
      institute of Human Relations, was the basis of Winternitz' interest in mental
      health. Although the institute soon closed because of interdisciplinary
      squabbling, this brief chapter in Yale's history illustrates the progressive
      thinking of the Dean and the pre-War place of psychiatry in medicine.

PMID- 7645311
TI  - [A meta-theoretical scope model of psychotherapeutic theories. Consequences for
      human image and therapy in behavior therapy].
AB  - Proceeding on the science-theoretical units Handeln, Tun and Verhalten, developed
      by Groeben 1986 connected with an integration of empirical and hermeneutical
      investigation, a metatheoretic frame model of psychotherapeutic theories is
      presented and its relevance for the practice is explained. The model integrates
      different therapeutic ways with another and lays down an ethic-sequential order
      of rank for the choice of theories and methods, which orientates itself according
      to the basic main assumptions (qua assumptions of man-picture) of the different
      theories. Starting out from the epistemological subject model (Groeben & Scheele,
      1977) as another derivation of the model, an embedding of therapeutic action in a
      therapist-client-relationship is required, which is characterized with mutual
      structural parallelism. Goal of therapeutic intervention is the re-establishment
      of Handlungs-capacity of the client, as postulated in the self management
      approach. Because of its initial behaviouristic tradition especially the
      behaviour therapy has to struggle with immense image problems concerning its
      assumptions of man-picture. Up to now a science-theoretical clarification of
      these problems has only been occurred in dissatisfied approaches. The present
      work should fill in this desideratum.

PMID- 7645312
TI  - [Diagnosis of interpersonal problems in depressive disorders].
AB  - Questionnaires assessing interpersonal problems may be of relevance in the field
      of psychotherapy not only to determine therapeutic goals but also for predicting
      the quality of the therapeutic alliance. Our study on the clinical validity of
      the Inventory of Interpersonal Problems-IIP (Horowitz) focussed on patients with
      affective disorders. According to the literature we hypothesized two subgroups
      with different areas of problems: one with high interpersonal dependency, one
      with an overly autonomous stance. Our sample comprises 169 patients of a
      psychotherapeutic outpatient clinic for students with the diagnosis of an
      affective disorder according to ICD 10 and a partly (age, sex, subject)
      comparison group of 119 students. The IIP was able to replicate the
      aforementioned groups. The instrument therefore may be applied to measure change
      in depressive psychopathology. It also might offer help for differential
      indication in psychotherapy.

PMID- 7645313
TI  - [Intimate relations and the course of psychiatric disorders in relocated
      patients].
AB  - In this study we investigated empirically the association between close
      relationships and the course of psychiatric disorders in 94 persons who moved
      from the GDR to West Berlin in 1989 and showed psychiatric disorders after their
      arrival. The patients mostly suffered from anxious and depressive symptoms
      accompanied by vegetative complaints. Symptoms were clearly reduced within the
      follow-up period (follow-up interviews after 6 months and 2 1/2 years). There
      were moderate correlations between family situation and the degree of symptoms.
      The mere existence of a partnership was not found to influence improvement.
      Negative change of partnership, and more quarreling was associated with a more
      unfavorable course of illness. Living with children was correlated with more
      symptoms--particularly six months after migration--and may be an additional
      stress factor for successful adaptation.

PMID- 7645314
TI  - [A new development in the treatment of anxiety and trauma: "eye movement
      desensitization and reprocessing (EMDR)"].
AB  - This article presents a new development on the field of psychotherapy: Eye
      Movement Desensitization and Reprocessing (EMDR). This recently developed
      procedure promises rapid and effective treatment of anxiety related complaints,
      including post-traumatic stress disorders (DSM-III-R). In essence the therapist
      induces a series of rapid and rhythmic eye-movements. EMDR facilitates cognitive
      changes and lasting decrease of anxiety. As indicated by research and illustrated
      by case histories, EMDR can be effective in one session. Until now there is no
      definitive explanation for the effectiveness of this method.

PMID- 7645315
TI  - [Attribution-changing measures in psychotherapy and medicine: theoretical
      foundation, applications and success].
AB  - Attributional changes in psychotherapy and medicine: Theory, application, and
      success. The treatment of eating disorders and diabetes, of smoking and
      hypokinesis is closely related to patients' attributions. Non-supporting
      attributions frequently excuse patients' lack of motivation to change risk
      behaviors sometimes, as with anorectic behavior, they even underline patients
      power to control their behavior. Critical experiences leading to patients' non
      supporting attributions are reconstructed on the basis of Kelley's (1967)
      attribution theory; after defining supporting attributions for various diseases
      and health risks the critical information resulting in these attributions is
      defined. Corresponding changes in patients' attribution will reduce patients' non
      compliance and support success in therapy. Though little research is published on
      long-term effects of attributional changes, patients' belief in supporting
      attributions will stabilize therapy success.

PMID- 7645316
TI  - [Treatment of psychotic patients with music therapy].
AB  - The present contribution describes the experience taken from music therapy of
      psychotic patients. The emotional and cognitive music perception and its possible
      influence on self perception and strengthening of ego are discussed. Since
      exercise instructions were limited the observed improvement of communication
      seems rather due to intra- and interpersonal effects of active improvisation than
      to a training process. With regard to schizophrenic patients possible effects of
      music therapy are discussed in the light of self-object-differentiation.

PMID- 7645317
TI  - [The current status of reflex theory].

PMID- 7645318
TI  - [The cerebral interrelationships of cognitive and emotional activities: pathways
      and mechanisms].

PMID- 7645319
TI  - [The frequency characteristics of EEG spectra in emotions].
AB  - The study is devoted to analysis of EEG frequency spectral characteristics during
      mental reproduction by subjects of joy, anger, fear, and sorrow. Significant
      differences between the emotional states are revealed in the points C4, T4, F3,
      O1 by the mean alpha-frequency (p < 0.05). Two opposite tendencies are revealed,
      i.e., joy and anger are mainly characterized by an increase of the alpha peak
      frequency in respect to the background values, whereas its decrease is seen in
      fear and sorrow.

PMID- 7645321
TI  - [The creation of a defensive dominant during the functioning of a blinking
      dominant in the rabbit].
AB  - Possibility of formation of motor defensive dominant (by serial electrical
      stimulation) at the background of active blinking dominant was studied in chronic
      behavioral experiments in rabbits. Formation of motor defensive dominant under
      such conditions was a problem. When the active dominant focus was inhibited and
      symmetrical representation of the other eye was activated formation of motor
      defensive dominant was also problematic. Stable coexistence of the two dominants
      was not observed under conditions when one of them was formed at the background
      of the other.

PMID- 7645320
TI  - [The over-reinforced conditioned reflex--a highly adaptive behavioral system].
AB  - Specialized (according to Pavlov) instrumental alimentary conditioned reflexes
      (CR) were studied after extremely prolonged training (2500-3000 pairings). It was
      established that these CR were characterized by extremely rapid extinction (till
      15-20 absences of instrumental reaction after only 2-7 presentations of non
      reinforced conditioned stimulus, despite the classical statement on difficult
      extinction of consolidated CR) independently of typological features and level of
      alimentary motivation of animals. The results obtained allow us to set aside such
      reflexes as a special category of CR which are underlined by neurophysiological
      and neurochemical mechanisms distinct from those of commonly used in experimental
      practice less trained CR. The phenomenon described may be interesting in studying
      the processes of learning and long-term memory.

PMID- 7645322
TI  - [A systems analysis of the defensive behavior of Wistar rats during bilateral
      active avoidance training].
AB  - Formation of the new behavioral act (active avoidance in shuttle box), its
      relationship with other forms of defensive behavior were studied in Wistar rats.
      During learning all the forms of defensive behavioral and motor activity were
      recorded. In result of the cluster-analysis (ISODATA) some tactics of defensive
      behavior were described. The results are discussed according to Anokhin's theory
      of the functional system.

PMID- 7645324
TI  - [Numerousness judgement in hooded crows: generalization by the "more than"
      concept].
AB  - Four carrion crows were trained to choose the greater array from pairs of
      numerousness discriminanda in the range of 1-12. In the process of training all
      irrelevant attributes of the arrays (geometric form, size and color of elements,
      patterns of distribution) were varied. Several control procedures were employed
      to make extraneous cues unlikely. In particular, in order to preclude the use of
      cumulative area or other magnitude cues the ratio of cumulative area of elements
      to their number was varied (in a half of presentations the greater array
      consisted of bigger elements while the lesser array consisted of smaller elements
      and in the other half the greater array consisted of smaller elements while the
      lesser array consisted of bigger elements). All the crows demonstrated high
      accuracy of comparisons (75.3 +/- 2.4%). Correct performance dominated also under
      conditions with minimal difference between the compared arrays. It was concluded
      that these crows were able to compare the arrays in the range of 1-12 by
      numerosity itself. When arrays in the new range of 10-20 were presented all the
      crows demonstrated successful transfer of acquired reaction without any
      additional training (71.5 +/- 2.3%). However, when the ratio of cumulative area
      of elements to their number varied only two of the four crows performed
      successfully (71.9 +/- 3.6). Taken together these data suggest that crows are
      capable of forming the concept "more than" based on numerical discrimination up
      to 20.

PMID- 7645325
TI  - [The transfer of information about the quantitative characteristics of an object
      in ants].
AB  - In the laboratory experiments devised on the basis of the Information Theory,
      ants (Formica polyctena Foerst.) had to transmit definite information on the
      number and coordinates of objects. One of the experimental sets consisted of a
      long "trunk" with branches ended in an empty trough, except for one filled with
      sugared water. Another set consisted of the lattice which simulated Cartesian
      coordinates. Ants had to learn position of the through and transmit its
      coordinate on the lattice. Obtained results suggest ants as being able to
      estimate the number of objects and transmit this information to their nest mates
      as well as the information on the coordinates of objects.

PMID- 7645323
TI  - [The behavioral phenomenon of "parasitism" in rats].
AB  - 29 male Wistar rats had been individually trained pressing the bar and receiving
      the rewards in the box with the feeder-cup and the bar attached to the opposite
      walls. Constant pairs of rats were formed. Behavior of rats in pairs was observed
      during 100 sessions in the same box. As a rule, one of the rats performed most of
      the bar pressings ("a worker") while its partner received the rewards without
      "working" ("a parasite"). It was possible to classify rats in four groups by
      their behavior, i. e. "parasites", "working", rats which changed their behavior
      from "working" for "parasitic" type and vice versa in the course of the
      experiment, and rats from the pairs where both partners extinguished bar pressing
      reflex near to zero level. Correlation was shown between behavioral type of rats
      in paired experiment and individual typological characteristics of fear reaction
      to different stimuli. Tests of open field behaviour, reaction of choice between
      the burrow and illuminated area, and emotional resonance were used for testing
      fear reaction.

PMID- 7645326
TI  - [The orienting reaction in invertebrates].
AB  - There are described the changes in movement and autonomous activity of the
      freshwater crayfish upon the sudden changes of the environment. The judging the
      reaction was based on: 1) the observation of all available behavioral
      manifestations in the crayfish Procambarus cubensis which has been in its
      "natural" habitat; 2) the recording of the electrical activity of the heart (ECG)
      and of the ventilatory appendages (scaphognathites; SGG) in freely moving Astacus
      astacus and Procambarus cubensis; 3) the non-invasive recording of Procambarus
      cubensis background locomotion in the conditions close to natural ones. It was
      concluded that even being immobile crayfish is continuously watching its
      surrounding and is revealing its very slight changes. It is suggested that
      crayfish response to "neutral" stimulus arising in the environment is rather
      similar to the orienting response of higher mammals. It is possible to suggest
      too the appearance in this situation of the emotional reaction in the crayfish.

PMID- 7645328
TI  - [The evoked activity of the lateral hypothalamus during extinction and
      differential inhibition].
AB  - Character of interaction between symmetric points of the cat's auditory cortex
      (A1) and the lateral hypothalamus (HL) was determined by calculating Spearman
      correlation coefficients between averaged summed sound-evoked activity (AEP) of
      the structures before, during elaboration, extinction and restoration, as well as
      differentiation of food-procuring conditioned reflex and in the eating full.
      Close mutual co-tuning between the cortex and hypothalamus characteristic for
      stable conditioned reflex was found to disrupted during its extinction,
      elaboration of differentiation and fullness eat inhibition due to entire
      reduction of hypothalamic AEP and disappearance of correlated with negativity of
      HL AEP "doubling" of the first positive wave of A1 AEP. Hyperactivity stage,
      expressed at the beginning of extinction and at the end of differentiation,
      preceded inactivation of hypothalamic afferents during elaboration of conditioned
      inhibition. The stage of hyperactivity, initiated by the elevated emotional state
      of the animal, testifies to an important role of emotional brain structures in
      the process of internal inhibition. The stage of HL and A1 hyperactivity
      initiated by emotional stress of the animal and following HL inactivation during
      inhibition of the conditioned response point to an important role of emotional
      subcortical brain structures in the mechanisms of inhibitory conditioning.

PMID- 7645327
TI  - [An EEG coherence analysis during the interaction of a motor polarization
      dominant and "animal hypnosis" in rabbits].
AB  - Intercentral relations of electrical activity of sensorimotor and premotor
      cortical areas of the right and left hemispheres were studied by means of
      coherence analysis during interaction of "animal hypnosis" and motor polarization
      dominant created by the action of DC anode on the area of the left hemisphere in
      rabbits. It was shown that the session of the "animal hypnosis" performed on the
      background of the optimum of polarization dominant elicited disappearance of
      asymmetry of coherence in the delta-range frequency of electrical activity of the
      examined cortical areas. After the end of hypnotic state and appearance of the
      motor reaction of the "non-dominant" right limb to the test stimulus, right-left
      asymmetry was again observed in coherence spectra of electrical activity of
      sensorimotor and premotor cortical areas. This phenomenon of was characteristic
      for the optimum of polarization dominant.

PMID- 7645329
TI  - [Long-term changes in the efficiency of inhibitory transmission in the
      thalamocortical neuronal networks evoked by cortical microstimulation].
AB  - Long-term posttetanic modifications of the efficacy of inhibitory synaptic
      connections were studied in auditory thalamo-cortical assemblies. We demonstrated
      that intracortical microstimulation (ICMS, high-frequency pulse of 5 mcA) which
      activated a small group of cortical neurons produced long-term (at least 30 min)
      modifications (potentiation--LTPi and depression--LTDi of the efficacy of
      inhibitory monosynaptic transmission between numerous elements of thalamo
      cortical network. LTPi was accompanied by an increase in the firing rate of
      inhibitory neuron. LTPi was input-specific and did not lead to decrease in the
      firing rate of the postsynaptic cell. LTP of the efficacy of excitatory and
      inhibitory inputs of the same target cell could be induced simultaneously. The
      efficacy of inhibitory synapses formed by the terminals of one axon on different
      cells could be modified variously. These results allowed us to suggest that we
      dealt with inhibitory synapses located on dendritic spines and that both pre- and
      postsynaptic mechanisms could underly long-term modifications of inhibitory
      transmission.

PMID- 7645330
TI  - [Changes in the monoamine content of the brain influence the reaction of
      emotional resonance].
AB  - Influence of 5-hydroxytryptophan (5HTP) and disulfiram on a reaction of emotional
      resonance (RER) was studied in two groups of female rats: I--with good and II-
      with poor elaboration of RER and, correspondingly, with the minimal and the
      maximal time of stay in the dark compartment. One week after 5HTP injection good
      elaboration of RER in animals of the I group was substituted for poor. In the II
      group of animals RER was unchanged. Injection of disulfiram increased the stay in
      the dark compartment in the I group and decreased it in the II group. At the same
      time dopamine content in the midbrain and medulla increased. The results confirm
      the hypothesis on participation of monoamines and their different contribution in
      RER realization in different groups of animals.

PMID- 7645332
TI  - [The subjective assessment of duration by cross-modality matching in children and
      adults].

PMID- 7645331
TI  - [The mitotic activity of the cells in the head neural ganglion in larvae of the
      Drosophila ts mutant with an altered capacity for learning and augmented
      calmodulin activation properties].
AB  - Mitotic activity of head neural ganglion cells of Drosophila melanogaster larvae
      from two genetic stocks was studied. The mutant stock agts3 with augmented
      activatory potentialities of calmodulin and modified capacity for learning was
      compared with the control wild type Canton-S stock. The mitotic index was defined
      as the ratio of the number of cells in the state of division to the total cell
      number. The mitotic index was calculated after 30-min incubation of the larvae at
      the temperature of 37 degrees C and without heating under normal conditions (22
      degrees C). At 22 degrees C the mitotic index in agts3 was higher than in CS.
      Exposure to 37 degrees C led to a sharp decrease of mitotic activity in both
      stocks. Increased mitotic index in agts3 stocks at 22 degrees C was probably
      connected with augmented activatory potentialities of calmodulin. After
      preincubation of the neural ganglions with calmodulin inhibitor trifluoperazine
      (10(-3)M) for 30 minutes the difference between the mutant and control stocks in
      mitotic index disappeared due to its approximately 3-fold decrease in agts3
      stock. The obtained results supported the proposed hypothesis and demonstrated
      importance of calmodulin as a regulator of mitotic activity of cells from the
      neural ganglion of Drosophila larvae.

PMID- 7645333
TI  - [Functional biofeedback control as a procedure for correcting the
      psychophysiological status of a child].

PMID- 7645334
TI  - [Sex differences in speech perception in children and adults].

PMID- 7645335
TI  - [The role of social factors in skill performance in a group of chimpanzees].

PMID- 7645336
TI  - [The mechanisms of the effect of a vasopressin analog on the efficiency of
      glutamatergic transmission in the hippocampus].

PMID- 7645337
TI  - [Changes in the defensive reaction of rats under the influence of the delta sleep
      inducing peptide].

PMID- 7645339
TI  - [The computer analysis of the EEG and EP: the problems and solutions].

PMID- 7645338
TI  - [The effect of serotonin antibodies on the conditioned reflex of passive
      avoidance in rats].

PMID- 7645340
TI  - [The determination of right and left handiness by motor reaction asymmetry].

PMID- 7645341
TI  - [Asratian's antishock solution].

PMID- 7645342
TI  - [The "multiple entropy" index in EEG analysis].

PMID- 7645343
TI  - Isolation and biochemical characterization of organelles from the yeast,
      Saccharomyces cerevisiae.

PMID- 7645345
TI  - The peculiarities of the interaction of radiation and hyperthermia in
      Saccharomyces cerevisiae irradiated with various dose rates.
AB  - In experiments with yeast cells it was shown that the synergistic effect of a
      simultaneous action of ionizing radiation and hyperthermia was a function of dose
      rate. It was demonstrated that, with increasing dose rate to obtain maximum
      synergistic effect, the temperature at which radiation is delivered should by
      elevated. Possible explanation of this effect is discussed.

PMID- 7645346
TI  - Automatic intron detection in nuclear DNA sequences of Saccharomyces cerevisiae.
AB  - The goal of the present work is the construction of software (EXPLORA) which
      automatically detects Open Reading Frames (ORF), intron-containing or not, in the
      nuclear sequences of the yeast Saccharomyces cerevisiae. In order to detect
      introns within (or preceding) ORFs, one must define precise rules of how an
      intron is identified. These rules are described here. The software is able to
      detect correctly an intron-associated ORF in at least 88% of cases. We tested all
      yeast nuclear entries of the EMBL database with the software, and found, in
      addition to the known intron-associated ORFs, some others which may include an
      intron. Finally the software was applied to the DNA sequences of chromosomes III
      and XI, in which it detected eight new intron-associated ORFs.

PMID- 7645344
TI  - Mutations sensitizing yeast cells to the start inhibitor nalidixic acid.
AB  - The regulatory step Start in the cell cycle of the budding yeast Saccharomyces
      cerevisiae is inhibited by nalidixic acid (Nal). To study this inhibition,
      mutations were identified that alter the sensitivity of yeast cells to Nal. Nal
      sensitive mutations were sought because the inhibitory effects of Nal on wild
      type cells are only transient, and wild-type cells naturally become refractory to
      Nal. Three complementation groups of Nal-sensitive mutations were found.
      Mutations in the first complementation group were shown to reside in the ARO7
      gene, encoding chorismate mutase; tyrosine and phenylalanine synthesis was
      inhibited by Nal in these aro7 mutants, whereas wild-type chorismate mutase was
      unaffected, These aro7 alleles demonstrate 'recruitment', by mutation, of an
      innately indifferent protein to an inhibitor-sensitive form. The Nal-sensitive
      aro7 mutant cells were used to show that the resumption of Nal-inhibited nuclear
      activity and cell proliferation takes place while cytoplasmic Nal persists at
      concentrations inhibitory for the mutant chorismate mutase. Mutations in the
      second complementation group, nss2 (Nal-supersensitive), increased intracellular
      Nal concentrations, and may simply alter the permeability of cells to Nal. The
      third complementation group was found to be the ERG6 gene, previously suggested
      to encode the ergosterol biosynthetic enzyme sterol methyltransferase. Mutation
      or deletion of the ERG6 gene had little effect on the inhibition of Start by Nal,
      but prevented recovery from this inhibition. Mutation of ERG3, encoding another
      ergosterol biosynthetic enzyme, also caused Nal sensitivity, suggesting that
      plasma membrane sterol composition, and plasma membrane function, mediates
      recovery from Nal-mediated inhibition of Start.

PMID- 7645347
TI  - Sequencing analysis of a 15.4 kb fragment of yeast chromosome XIV identifies the
      RPD3, PAS8 and KRE1 loci, five new open reading frames.
AB  - The DNA sequence of a 15.4 kb region covering the left arm of chromosome XIV from
      Saccharomyces cerevisiae was determined. This region contains eight open reading
      frames (ORFs) which code for proteins of more than 100 amino acids. Three ORFs
      correspond to the RPD3, PAS8 and KRE1 loci, described previously. Three ORFs show
      limited homology with known proteins: NO330 with the recessive suppressor of
      secretory defect SAC1, NO325 with YCR094W identified during chromosome III
      sequencing; whereas NO315 presents a motif conserved in the dnaJ family. Two ORFs
      (NO320 and NO325) show no homology to known proteins within the databases
      screened, but NO320 corresponds to a serine-threonine-rich protein. The sequence
      has been entered in the EMBL data library under Accession Number Z46259.

PMID- 7645348
TI  - The upstream sequences of the HSP82 and HSC82 genes of Saccharomyces cerevisiae:
      regulatory elements and nucleosome positioning motifs.
AB  - We present the upstream sequences of HSP82 and HSC82, two closely related, but
      differentially regulated, heat-shock genes of Saccharomyces cerevisiae. Several
      dozen potential regulatory elements are identified within each upstream region;
      interestingly, only a few are conserved between the two genes. These include a
      consensus heat-shock element, an upstream repressor element, and a consensus TATA
      element. A search for motifs known actively to position nucleosomes in vitro
      revealed that such sequences are three- to seven-fold enriched within each
      promoter; a comparable enrichment is seen near the 3' end of each transcription
      unit. Located approximately 1100 bp upstream of HSC82 is an open reading frame
      (ORF) of 255 amino acids; approximately 800 bp upstream of HSP82 is an ORF of 132
      amino acids. The latter ORF contains several conserved ankyrin motifs and appears
      to be expressed under normal growth conditions. Finally, we show by clamped
      homogeneous electric field gel electrophoresis that the two genetic loci map to
      different chromosomes: HSP82 to chromosome XVI and HSC82 to chromosome XIII. The
      sequences have been deposited in the GenBank database under Accession Numbers
      U20323 and U20349.

PMID- 7645349
TI  - Identification and initial characterization of the cytosolic protein Ycr77p.
AB  - The nucleotide sequence of yeast chromosome III encompassing the previously the
      previously described open reading frames (ORFs) YCR80w, YCR77c and YCR78c (Oliver
      et al., 1992) has been updated. In the corrected sequence, these ORFs are
      replaced by two new ORFs, YCR80w (453 bp) and YCR77c (2391 bp). In addition, the
      orientation of Ycr79c is reversed to give ORF Ycr79w, which has an unaltered nt
      sequence. The predicted translation products do not exhibit significant homology
      to known proteins. ORF Ycr77p encodes an 88 kDa, cytosolic protein. A fraction of
      the protein is associated with small membranous structures in a salt-sensitive
      fashion. Initial characterization revealed that the protein is not essential for
      yeast viability, growth on non-fermentable carbon sources, mating and
      sporulation. The chromosome III DNA sequence that was used for the analysis has
      the Accession Number X59720 in the GenBank/EMBL database.

PMID- 7645350
TI  - The complete sequence of a 9037 bp DNA fragment of the right arm of Saccharomyces
      cerevisiae chromosome VII.
AB  - We report the sequence of a 9037 bp fragment from the right arm of Saccharomyces
      cerevisiae chromosome VII. Analysis of the sequence revealed four complete open
      reading frames (ORFs), namely G7572, G7576, G7579 and G7584. The first three
      corresponded, respectively, to the previously cloned genes: HIP1, coding for a
      high-affinity histidine-specific permease, TDH1, one of the known genes coding
      for glyceraldehyde-3-phosphate dehydrogenase and ODPX, which encodes a precursor
      of protein X, a component of the pyruvate dehydrogenase complex. The ORF G7584
      showed 35.8% identity with a hypothetical protein of Caenorhabditis elegans
      chromosome 3. The reported sequence has been deposited in the EMBL data library
      under Accession Number X82408.

PMID- 7645351
TI  - Current awareness on yeast.

PMID- 7645352
TI  - [Hormone substitution in climacteric. Position of the German Menopause Society].

PMID- 7645354
TI  - [Prevention of thrombosis with low molecular weight heparin in gynecology].
AB  - An observational study on the use of low molecular weight heparin (LMWH)
      Fraxiparin 0.3 was performed at the Department of Obstetrics and Gynaecology of
      the University Hospital of the Saarland, Homburg/Saar. The aim of the study was
      to investigate effectiveness and safety of this LMWH in obstetric and
      gynaecological surgery for patients with mostly intermediate risk for
      thromboembolism. We observed 484 women, aged between 14 and 84 years, the
      majority of whom underwent surgery for benign or malignant gynaecological tumours
      including breast tumours. 40 patients had obstetrical problems. The patients were
      given a single daily dose of Fraxiparin 0.3 subcutaneously, beginning on the
      preoperative day until they were discharged from hospital. In addition, the
      patients wore antiembolic stockings during the whole period of observation. No
      thromboembolic events were observed clinically. Normal intraoperative blood loss
      was observed in 86%, normal postoperative seroma drainage in 74% of cases. During
      the study period wound haematomas were seen in 7 patients. There was in no case a
      direct causal link to Fraxiparin treatment. These results are in conformity with
      previous clinical studies and drug monitorings and emphasize the effectiveness
      and safety of thromboembolism prophylaxis with low molecular weight heparin also
      in obstetrics and gynaecology.

PMID- 7645353
TI  - [Proteins in uterine secretions of fertile and sterile patients using SDS
      polyacrylamide gel electrophoresis (SDS-PAGE)].
AB  - Aim of the presented study was to find out whether there are any differences in
      the protein patterns of uterine secretions of fertile and sterile women. Analysis
      was made by polyacrylamide gel electrophoresis (SDS-PAGE). Uterine secretions and
      sera of 11 sterile and 8 fertile patients were investigated. Utilizing the
      reducing SDS-electrophoresis, the comparison of all uterine secretions revealed
      an additional protein band of molecular weight of 33,000 Dalton in the uterine
      secretions of the fertile women. Secretions of the sterile women showed a protein
      band which was of significantly lower weight. The significance of this additional
      protein band as a possible factor of fertility is discussed.

PMID- 7645355
TI  - [Inflammatory pseudotumor the bladder wall after abdominal hysterectomy for
      uterine myoma].
AB  - We report on a 49-year-old woman who underwent an abdominal hysterectomy for
      uterine myoma. Six months after the primary surgery a 2 x 2 cm tumor was detected
      in the posterior wall of the urinary bladder. This tumor was associated with
      pain, dyspareunie and voiding disturbances. A repeat-laparotomy and partial
      resection of the urinary bladder were carried out. The histological and
      immunohistochemical examinations revealed an inflammatory pseudotumor of the
      urinary bladder. Similar lesions after surgery on the genito-urinary system were
      previously reported mainly in the urinary bladder. Difficulty may arise in
      differentiation of these lesions from low-grade leiomyosarcomas.

PMID- 7645356
TI  - [Does measurement of absolute velocity by Doppler examination of pregnant
      patients contribute additional valuable information?].
AB  - Ultrasonics is very important for the control of risk pregnancies. Routinely,
      Doppler-ratios are used to assess fetal danger. The aim of the presented study
      was to clarify whether measurement of absolute blood flow velocity is useful for
      the assessment of fetal development as well. For this purpose we examined the
      fetal aorta in 149 patients: 90 patients with fetal growth retarded fetuses and
      59 patients with normally developed fetuses. Systolic and diastolic peak
      velocities and the resistance index (RI) were measured. The absolute velocities
      did not show any correlation to the fetal growth. Moreover, there was no
      correlation between systolic peak velocity and resistance index, independent of
      degree of pathology. The diastolic peak velocity however correlated with high
      significance to the RI thus being directly dependent.

PMID- 7645357
TI  - [Good sense and nonsense in tocolysis].
AB  - The present paper tries to evaluate the importance of tocolysis with beta
      sympathomimetic drugs twenty years after their introduction into obstetrics.
      Intrauterine resuscitation and short-term tocolysis have proven to be very
      effective during this period of time. Because of potential side effects long-term
      tocolysis has to be considered dangerous and apparently not effective. Oral and
      prophylactic tocolysis are ineffective. When considering prevention of premature
      delivery one has to be aware of the fact that premature contractions are only
      ostensible symptoms of a complex event.

PMID- 7645358
TI  - [The value of laparoscopy in diagnosis and therapy in patients with chronic
      pelvic pain].
AB  - The anamnesis, the preoperative diagnostics, the laparoscopic findings, and the
      therapeutic management are reported of 303 patients who underwent laparoscopy
      because of chronic pelvic pain during the years of 1989 and 1993. The most common
      laparoscopic diagnosis were adhesions of the bowel and omentum (34.7%), adhesions
      of the genital organs (24.1%) and endometriosis (19.8%). In 31.4% there were
      normal pelvic findings. In patients with a history of surgical or other
      gynecological procedures we found significantly more adhesions as compared to
      nontreated controls; the adhesions were predominantly confined to the bowel and
      rather than the gynecologic pelvis. PID-Patients had significantly more genital
      adhesions. The high frequency of surgical laparoscopies and therapeutic
      recommendations following a diagnostic laparoscopy emphasize the importance of a
      laparoscopic investigation in patients with chronic pelvic pain.

PMID- 7645359
TI  - [Overview of the development of laparoscopic surgery at the gynecologic clinic of
      the Leipzig University 1989-1993].
AB  - This paper reports on the trend in pelviscopy at the women's Hospital of the
      University of Leipzig during the period from 1989 to 1993. There were 1989
      operations performed. Most of them (50.2%) were of diagnostic nature, followed by
      tubal sterilization (39.8%). Endoscopic surgery was represented with 9.9% of
      pelviscopy. Complication rate was at 0.6%. Mortality rate was at 0.05%. Since
      tubal sterilization has been introduced in 1990, a number of 792 patients have
      been sterilized by endocoagulation according to the method of Semm. Sterilization
      failure was at 0.38%.

PMID- 7645360
TI  - [Extrauterine pregnancy after hormonal postcoital contraception].
AB  - Postcoital contraception with estrogen-gestagen-combinations is a highly
      effective emergency measure in cases of unprotected sexual intercourse at
      midcycle. Pregnancies after hormonal postcoital contraception are rare and
      ectopic pregnancies are said to be an extreme rarity. At the Department of
      Obstetrics and Gynecology of the Philipps-University Marburg we could observe two
      women with ectopic pregnancies after administration of a ethinyestradiol
      levonorgestrel combination (Tetragynon, Schering, Berlin). Both patients were
      operated by pelviscopy. We could not found a clear causal relationship between
      the administration of hormonal postcoital contraception and ectopic pregnancies,
      because both women had intrauterine operations in her history and therefore a
      certain level of tubal damage could not ruled out. Nevertheless, in cases of
      hormonal postcoital contraception a follow-up check after 3 weeks should be done
      and it should be kept in mind that ectopic pregnancies may occur, especially in
      patients with risk factors.

PMID- 7645361
TI  - [Ovarian metastasis of malignant melanoma--case report].
AB  - Malignant melanoma is a rare encounter in gynaecological practice; when it does
      occur it is most commonly as a primary tumor of the vulva. Primary manifestation
      of generalised metastatic spread in both ovaries ten years after treatment for a
      low risk malignant melanoma is a rare finding. In the absence of a appropriate
      previous history, classical histopathological methods can sometimes lead to an
      uncertain diagnosis. However, by permitting a combination of various markers,
      supplemental immunohistochemical examination will facilitate the correct
      diagnosis.

PMID- 7645362
TI  - [Meeting of the Saxony Society of Gynecology and Obstetrics 23 April 1994 in
      Chemnitz].

PMID- 7645363
TI  - [Interferon-alpha-induced disorders of thyroid function. A retrospective analysis
      of the literature and personal experiences].
AB  - This paper tries to evaluate the importance of IFN-alpha induced thyroid
      dysfunction. Based on our own experience and reported data we present the results
      obtained in a total of 588 patients, in whom thyroid function and thyroid
      antibody occurrence was monitored during therapy with IFN-alpha: About 10% of
      these patients developed thyroid dysfunction during IFN-alpha treatment. Half of
      them reacted with hypothyroidism, 3% with hyperthyroidism and in 2% a biphasic
      (hyperthyroidism followed by hypothyroidism) pattern of reaction was observed.
      The frequency of these thyroid dysfunctions was increased in female patients and
      in patients with preexisting thyroid antibodies. The risk to develop thyroid
      dysfunction is reduced to 7% in patients with no pretherapeutic thyroid
      antibodies. The evolution of the thyroid ailment is variable and therefore
      unpredictable. In many patients there is no need to stop treatment with IFN-alpha
      nor to treat the thyroid dysfunction specifically. IFN-alpha induced autoimmune-
      phenomena seem to be etiologically important for the development of thyroid
      disease during IFN-alpha. The reported data allow in our view some basic
      recommendations for the clinician: thyroid function and thyroid antibodies should
      be evaluated before the start of treatment with IFN-alpha. During therapy with
      IFN-alpha these parameters should be regularly (eg every 4 months) monitored. In
      patients with thyroid autoantibodies or dysfunction already before IFN-alpha the
      control intervals should not be longer than every two months.

PMID- 7645364
TI  - Physiological studies on heat exhaustion victims among Mecca pilgrims.
AB  - This investigation focuses on the hormonal response to electrolyte changes and
      water loss in patients suffering from heat exhaustion, hospitalized in Muna
      during Hajj seasons. The concentrations of cortisol, aldosterone, renin (PRA),
      vasopressin (ADH) parathyroid hormone (PTH), adrenocorticotrophic hormone (ACTH)
      and growth hormone (GH) were determined in venous blood samples drawn from the
      patients upon admission, during, and after treatment. Highly elevated PRA mean
      values (396.77 +/- 88.58-462.18 +/- 106.95 ng.ml-1.h-1) were recorded, with no
      statistically significant difference between the readings. A similar trend was
      seen for cortisol (42.92 +/- 4.30-60.20 +/- 11.90 ug/dl). Vasopressin (ADH)
      showed a highly elevated value upon admission (42.48 +/- 18.82 pg/ml), which
      decreased to 23.66 +/- 8.27 pg/ml during treatment, and declined further to 7.67,
      ranging between 4.04 and 11.30 pg/ml, thereafter. Statistically speaking,
      however, there was no significant difference between these readings. PTH
      concentration, on the other hand, increased from an initial value of 143.31 +/-
      47.64 to 245.90 +/- 107.34 pmol/l after treatment, but again there was no
      significant difference between the values. ACTH concentrations showed no
      detectable values throughout this study. The GH concentration was within normal
      throughout, ranging from 4.42 +/- 0.87 to 5.19 +/- 1.78 ng/ml. Aldosterone
      concentration was significantly reduced in the patients upon admission, with an
      initial value of 187.93 +/- 21.41 pg/ml (p < 0.05 as compared to normal mean
      value). During and after treatment, aldosterone values were still significantly
      lower than normal mean (152.63 +/- 13.47, p < 0.05; 145.2 +/- 17.55, p < 0.01,
      respectively), thereby shedding some light on the possible etiology of persistent
      metabolic acidosis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7645366
TI  - [Palindromic rheumatism--progression to erosive rheumatoid arthritis-
      presentation of 3 years treatment of a patient].
AB  - The 3-year course of treatment of a 35-year old male patient presenting with
      recurrent afebrile episodes of acute mono- or polyarthritis, periarthritis and at
      times paraarthritis of the left ankle and knee joint as well as the PIP and MCP
      joints of the hands is presented. The episodes lasted from a few hours up to
      several days, leaving no residual changes in the joints. After initial
      observation and treatment, palindromic rheumatism was diagnosed. During the
      second year of treatment, seroconversion from the rheumatoid factor negative to
      the rheumatoid factor positive arthritis form was established. In the third year
      of treatment, erosions of cartilage and bone in the left knee joint were
      confirmed radiologically. On the basis of the clinical picture, laboratory
      findings and radiologic changes in the joints, the diagnosis of erosive
      seropositive rheumatoid arthritis was made. The author stresses that the
      diagnosis "palindromic rheumatism" could be established sooner and more often,
      particularly if, regarding the typical clinical course and history, the
      possibility of this disease were taken into consideration at all.

PMID- 7645365
TI  - [Increased prevalence of serum IgA Chlamydia antibodies in obesity].
AB  - Obesity is metabolically related to diabetes type II. We have previously shown
      that seroactive (IgG- and IgA-Chlamydia antibody positive) chlamydial infection
      of asymptomatic patients is more frequent in type II diabetic patients than in
      nondiabetics, independent from metabolic control. Thus we investigated 119
      nondiabetic patients (66 +/- 9 years, HbA1c < 6%) of our department for
      seroactive chlamydia infection using an immunoperoxidase reaction and compared
      the results to the anthropometric data. The prevalence of seroactive chlamydial
      infection was significantly (p < 0.05) higher in the considerably overweight
      patients with a BMI > 30 kg/m2, both when compared to lean patients (BMI < 24
      kg/m2) and when compared to all those with BMI < 30 kg/m2. For slight to moderate
      obesity the prevalences were slightly (but not significantly) increased. Due to
      the fact that similar data were obtained for type II diabetic patients, an
      unknown relation to insulin resistance might be the underlying cause and should
      be further investigated.

PMID- 7645367
TI  - [The value of diagnostic and interventional endoscopy in acute, non-varicose,
      upper gastrointestinal hemorrhage].
AB  - There is a broad consensus about the benefits of emergency endoscopy in the
      diagnosis and treatment of acute upper gastrointestinal bleeding. The Wels
      General Hospital is a large teaching hospital where all emergency endoscopies are
      performed by the staff of the First Department of Internal Medicine. The reports
      of 11,078 esophagogastro-duodenoscopies performed between November 1987 and
      February 1993 were scrutinized by the authors and 980 cases identified where a
      clinical diagnosis of suspected upper gastrointestinal hemorrhage had been made.
      All together 156 patients showed signs of active or recent bleeding on endoscopy
      (Forrest Ia, Ib, IIa) and were selected as database for this analysis. We
      identified 64 patients with duodenal ulcers, 43 patients with gastric ulcers and
      15 patients with Mallory-Weiss-tears. Erosions, anastomotic ulcers, cancer and so
      called rare causes (Dieulafoy ulcers, mesenchymal tumors Hemobilia) were
      identified in 34 patients. Therapeutic endoscopy was performed in 69 patients
      (44.2%). For hemostatic therapy we used the injection method with epinephrine. 34
      patients underwent surgical therapy (13 cases underwent emergency surgery). 10 of
      156 patients 10 (6.4%) died secondary to their acute nonvariceal upper
      gastrointestinal hemorrhage.

PMID- 7645368
TI  - [Metamorphoses of lysosome shape in association with function].

PMID- 7645369
TI  - [Secretory pathway of atrial natriuretic peptide].

PMID- 7645370
TI  - [Role of en gene in the rostrocaudal polarity formation of the optic tectum].

PMID- 7645371
TI  - Nuclear proteins involved in cell division in the ciliate, Tetrahymena.
AB  - For the purpose of clarifying the presence of nuclear proteins which may induce
      cell division, we conducted experiments using ciliate Tetrahymena which can be
      synchronized at the G2 phase in the cell cycle easily by periodic heat shock
      treatment (HST): We obtained proteins from the nuclei isolated from the cells
      grown at the early mid log-phase, at the G2 phase (60 min) and at the G1 phase
      (150 min), after HST. The proteins were studied by comparing the spots separated
      by isoelectric point, 10-20% gradient SDS two-dimensional electrophoresis. As a
      result, in comparison with the intranuclear protein at the log-phase, the
      proteins at the G2 phase showed a marked increase, but with no great change in
      the electrophoretic pattern. Meanwhile, the proteins at the G1 phase differed
      greatly from those at the G2 phase not only in the quantitative changes, but in
      the electrophoretic patterns. It is considered that the level of the accumulation
      of the nuclear proteins which should be closely involved in cell division must
      increase markedly at the G2 phase and decrease at the G1 phase. We confirmed the
      presence of four proteins: pI 5.8 MW 68 kDa, pI 6.1 MW 75 kDa, pI 8.6 MW 48 kDa
      and pI 6.6 MW 57 kDa, and then prepared monoclonal antibodies using these nuclear
      proteins as antigens. Among them, the antibody (IgM) against the pI 8.6 MW 48 kDa
      polypeptide (p48) was recognized the nuclei by indirect immunofluorescence in
      ancellular system at the S, G2 and the mid-M phases. However, nuclei at the late
      M and G1 phases were not stained.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7645372
TI  - Accessory muscular bundles arising from biceps femoris muscle.
AB  - Two kinds of accessory muscle bundles arising from the long head of the biceps
      femoris muscle were encountered in a 20-year-old Turkish female cadaver during
      routine dissections. The one occurred on both sides, each arising from the lower
      portion of the long head of the muscle and passed deep to the fascia of the
      popliteal fossa to be inserted into the crural fascia. The other one which was
      observed only on the right side, arose from the upper portion of this head to be
      inserted into the semitendinosus muscle.

PMID- 7645373
TI  - Expression of a dopamine transporter in PC12h cells: an immunohistochemical study
      with an antipeptide antibody.
AB  - Two kinds of oligopeptides, based on the amino acid sequences of No. 217-232 and
      374-387 of a rat dopamine transporter, were designed and chemically synthesized.
      Five clones of the monoclonal antibodies against these peptides were produced
      with the in vitro immunization method. Two of them have recognized a protein of
      M(r) approximately 85,000 in a synaptosomal fraction of the rat striatum. It is
      probable that the protein M(r) approximately 85,000 corresponds to a dopamine
      transporter in the nerve terminal of the dopamine neurons in the striatum. The
      expression of dopamine transporter was immunohistochemically examined with these
      antibodies in PC12h cells. The immunoreactivity was detected on the surface
      membrane of the cells.

PMID- 7645374
TI  - [Confocal laser scanning microscopy of the rat cerebral microcirculation].

PMID- 7645375
TI  - HLA-DQB1 allele associates with idiopathic nephrotic syndrome in Japanese
      children.
AB  - HLA-DQA1 and -DQB1 genes were investigated in 30 Japanese children with
      idiopathic nephrotic syndrome (INS) using the polymerase chain reaction
      restriction fragment length polymorphism method. Compared with control children,
      there was a significant increase in the HLA-DQA1*0501, DQB1*0301 and DQB1*0601
      alleles, whereas the frequency of DQB1*0501 showed a significant decrease in the
      patients. The increase of DQA1*0501 can be explained as being a result of a
      linkage disequilibrium with DQB1*0301. The previous result demonstrating a
      positive association of DRw6 and DRw8 with INS is also assumed to be attributable
      to a linkage disequilibrium with DQB1*0301 and 0601. A total of 83% of patients
      compared with 37% of controls possessed DQB1*0301 and/or DQB1*0601 allele (P <
      0.001, RR = 8.6). Only these alleles have alanine at residue 13 and tyrosine at
      residue 26 in the hypervariable region in the Beta 1 domain of DQB1 gene. These
      findings suggest that the unique amino acid residues in the DQB1 gene may
      contribute to disease susceptibility in Japanese children with INS.

PMID- 7645376
TI  - Effect of calcium antagonist, nicardipine, on cerebral blood flow in
      postasphyxial newborn piglets.
AB  - An experiment was carried out in nine piglets within 24 h after birth (control
      group: four, nicardipine group: five) for the purpose of evaluating the effects
      of a calcium antagonist, nicardipine, on cerebral blood flow changes induced by
      asphyxia neonatorum. Under respiratory control with a mechanical ventilator, the
      animals were exposed to hypoxia. The inspiratory oxygen level was lowered at 15
      min intervals from 0.08 to 0.06 and then to 0.05. When bradycardia (heart rate;
      60/min or less) was observed, 100% oxygen, adrenaline, and sodium bicarbonate
      were administered for resuscitation. Nicardipine was administered at a dosage of
      10 micrograms/kg via bolus injection 30 min after the resuscitation. It was
      administered thereafter at a rate of 10 micrograms/kg per h. The cerebral blood
      flow was measured using a laser Doppler velocimeter. The cerebral blood flow,
      electroencephalograph (EEG), blood pressure, and heart rate were continuously
      measured for 120 min after the resuscitation. In the control group, the mean
      arterial pressure 35 min after the resuscitation was 60 mmHg or more. However,
      the cerebral blood flow was lower than the prehypoxia value in the animals with a
      mean arterial pressure of 75 mmHg or less. In the nicardipine group, the mean
      arterial pressure was lower, but the cerebral blood flow was higher than the
      prehypoxia value and cerebral ischemia was not induced. The mean arterial
      pressure 120 min after the resuscitation was 72.0 +/- 8.2 mmHg in the control
      group, while it was 56.7 +/- 7.5 mmHg in the nicardipine group. It was
      significantly lower in the latter.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7645377
TI  - Herpes zoster in children with bone marrow transplantation: Report from a single
      institution.
AB  - Herpes zoster (HZ) has been often observed after bone marrow transplantation
      (BMT) in childhood. The occurrence of HZ was reviewed in children who received
      BMT. The clinical features of HZ were reviewed in 44 children who underwent BMT
      at Kyushu Cancer Center. Among the 35 recipients with a history of varicella
      before BMT, several factors associated with BMT and the lymphocyte subsets were
      compared between the patients who developed HZ (HZ+ group) and those who did not
      (HZ- group). Twenty-two recipients (50%) developed HZ; in two-thirds of these
      cases (15/22: 68%), HZ occurred between 80 and 120 days after BMT (median 101
      days). The recipients treated with busulfan had a higher occurrence of HZ than
      those treated without it. The patients with Grade II-IV acute graft-versus-host
      disease (GVHD) developed HZ more frequently. In the HZ+ group, the absolute
      number of lymphocytes, CD3+, CD4+ or CD8+ cells at 3 months was significantly
      lower than that observed at 12 months after BMT and the CD4/CD8 ratio was
      significantly lower at 1 month than after 3 months of BMT. In conclusion,
      recipients were susceptible to HZ at around 100 days after BMT. The development
      of HZ may be associated with unbalanced T lymphocytes at that time.

PMID- 7645378
TI  - Immunological unresponsiveness and apoptotic cell death of T cells in measles
      virus infection.
AB  - The phenotypic alterations associated with T cells during measles virus infection
      have been demonstrated and an attempt has been made to show programmed cell death
      (PCD) of T cells activated in vivo. During the acute phase of illness, activated
      T cells increased rapidly. Memory T cells (CD45RO+), especially CD8+ memory T
      cells also tend to increase. During the recovery phase, CD8+ T cells declined
      rapidly, and naive (CD45RA+) T cells increased in numbers. The anti-CD3
      monoclonal antibody-induced expression of interleukin-2 receptor (CD25) was
      suppressed. However, the addition of phorbol 12-myristate 13-acetate (PMA) caused
      the significant recovery of CD25 expression. In addition, PCD of activated T
      cells from measles patients was induced in culture. After triggering of the T
      cell receptor-CD3 complex, cells became more susceptible to PCD. Interestingly,
      the addition of PMA could inhibit PCD of activated T cells. Taken together, these
      data suggest unresponsiveness and activation-induced cell death of T cells during
      the primary response to measles virus antigens, depending on the activation
      status of protein kinase C.

PMID- 7645379
TI  - Interferon-gamma therapy for infection control in chronic granulomatous disease.
AB  - Interferon (IFN)-gamma was subcutaneously administered to four patients with
      chronic granulomatous disease (CGD) in order to evaluate its effects in
      controlling infection. Patients 1 to 3 were all males, while patient 4 was
      female. In patients 2 and 4, the length of infection-associated hospitalization
      during the year of IFN therapy was significantly shorter than that during the
      whole observed period prior to IFN therapy. In patients 1 and 2, the length of
      hospitalization during a year of IFN therapy was shorter than that during 1 year
      prior to the therapy. Patient 3 exhibited no reduction in terms of the length of
      infectious disease during IFN therapy, because he suffered from a liver abscess
      before and during the therapy. As soon as the IFN therapy was stopped, patient 2
      developed pneumonia and lymphadenitis, which were promptly relieved by
      readministering the agent. During 1 year of IFN therapy, patients 1, 2 and 4
      showed no significant changes in either the nitroblue tetrazolium test, O2-
      production or the expression of NADPH oxidase components in neutrophils. On the
      other hand, the O2- generating ability of neutrophils from patient 3 slightly
      increased. Our limited observations suggest that IFN-gamma may be variably
      beneficial for infection control in CGD-patients, irrespective of the in vitro
      phagocyte functions. A longer follow-up time is needed to confirm the IFN
      response in CGD-patients.

PMID- 7645380
TI  - Outbreak of pertussis in highly immunized adolescents and its secondary spread to
      their families.
AB  - An outbreak of pertussis was recognized in a highly immunized sixth-grade class
      of schoolchildren. Among 43 children aged 11-12 years in the class, 38 had been
      immunized with three doses or more of DTP containing whole-cell pertussis
      vaccine, two with two doses of DTP and three children were unimmunized. The last
      DTP vaccines had been given 6-10 years before the outbreak. A total of eight
      children with pertussis suffering paroxysmal coughing attacks for 3 weeks or more
      were identified, seven being fully immunized and one unimmunized. Among the eight
      cases, two were confirmed by both culture and serology and one by serology alone.
      The attack rate in fully immunized children was 18.4% (7/38). Secondary spread of
      pertussis was identified in five of the households from which the eight patients
      originated. A total of six cases of pertussis from these five households were
      identified, and two of these were culture-confirmed. These observations suggest
      that vaccine-induced immunity weakens considerably 6-10 years after vaccination,
      and that booster immunization with DTP instead of DT is therefore recommended for
      the control of pertussis.

PMID- 7645381
TI  - Autoantibodies and CD5+ B cells in childhood onset immune thrombocytopenic
      purpura.
AB  - We evaluated platelet associated immunoglobulin (PIag) G, PaIgM, platelet
      associated autoantibodies to platelet glycoprotein IIb/IIIa (Pa-GPIIb/IIIa), the
      percentage of CD5+ B cells and the amount of platelet-bound anti-GPIIb/IIIa
      monoclonal antibody (mAb) in the peripheral blood of 29 patients with childhood
      onset chronic immune thrombocytopenic purpura (c-ITP). The percentage of CD5+ B
      cells ranged from 2 to 8% (4.7 +/- 2.0) in control patients and 1 to 18% (6.2 +/-
      4.2) in the ITP patients. There was no overall significant difference between the
      two groups, but the percentage of CD5+B cells in six of the ITP patients was
      higher than the mean + 2 s.d. of the controls. There was a significant
      correlation between the percentage of CD5+ B cells and PaIgM (y = 1.73x + 13.4,
      r=0.40, P < 0.05). This finding is the basis for the speculation that CD5+ B
      cells may play an important role in the production of PaIgM in vivo. There was no
      correlation between the amounts of PaIgG and Pa-GPIIb/IIIa). This suggests that
      the amount of PaIgG does not accurately reflect of the amount of Pa-GPIIb/IIIa.
      Furthermore, we have demonstrated that autoantibodies to GPIIb/IIIa are directed
      to more that one epitope.

PMID- 7645382
TI  - Clinical patterns of X linked agammaglobulinemia in Malaysian children.
AB  - X linked agammaglobulinemia (XLA) is rarely reported from developing countries
      especially from South East Asia. It appears that X linked agammaglobulinemia is
      less common in certain ethnic groups. It is very uncommon in black people in USA
      and South Africa. In multiracial Malaysia we have documented five XLA in Malays
      and Indians but not in the Chinese that constitute about 31% of the population.
      First degree relatives afflicted with XLA or other primary immunodeficiencies
      occurred more often in our study. All showed lung involvement although the
      etiologic organisms involved were atypical, being Gram negative.

PMID- 7645383
TI  - Bronchial hyper-responsiveness to inhaled histamine in children with congenital
      heart disease.
AB  - In order to assess bronchial responsiveness in patients with congestive heart
      failure secondary to congenital heart disease, we performed a histamine
      inhalation test while monitoring transcutaneous oxygen tension and compared the
      respiratory threshold to histamine with that obtained in patients with bronchial
      asthma. The inhalation test was performed by doubling concentrations of histamine
      solution for 2 min at 1 min intervals. The respiratory threshold of histamine was
      defined as the minimal concentration causing a drop in transcutaneous oxygen
      tension greater than 10% from baseline. Six of 10 patients with congenital heart
      disease and all of 12 patients with bronchial asthma had bronchial hyper
      responsiveness to histamine. The mean of histamine concentration was 2750
      micrograms/mL and 937 micrograms/mL, respectively. During the histamine
      inhalation test, respiratory resistance gradually increased in congenital heart
      disease patients. This was measured by the linear slope of transcutaneous oxygen
      pressure (-1.08 +/- 0.75 mmHg/min), whereas in the bronchial asthma patients it
      rapidly decreased at the infection point (-4.19 +/- 1.86 mmHg/min). We conclude
      that children with congestive heart failure had bronchial hyper-responsiveness.
      We suggest bronchial hyper-responsiveness to inhaled histamine in congestive
      heart failure was caused by the gradual increased respiratory resistance, which
      was different from that of bronchial asthma.

PMID- 7645384
TI  - Abnormal cardiac histology in severe intrauterine growth retardation infants.
AB  - Four infants with severe intrauterine growth retardation (IUGR) weighing less
      than 1000 g at birth developed heart failure and died in our unit, where heart
      failure of IUGR infants is the main reason of death in extremely low birth-weight
      infants. The causes of their heart failure are one of the main themes in current
      neonatal medicine. The subjects of this study were four small for gestational age
      infants; all died due to heart failure 5 to 10 days after birth. Microscopic
      specimens of hearts from autopsies were evaluated with respect to the following
      characteristics: thickness of myocardial fibers, maturation of nuclei, presence
      of dysgenesis or necrosis in myocardium, and amount of glycogen in the heart.
      Neither dysgenesis nor infarction of the heart was found but hypoplasia in
      myocardial fibers and decreased glycogen levels were observed. Maturation delay
      in myocytes' nuclei did not appear to be severe. We conclude that these infants'
      hearts failed to adapt to postnatal hemodynamic changes because of inadequate
      myocardial function and inadequate glycogen reserves.

PMID- 7645385
TI  - Association of empty sella and neuroendocrine disorders in childhood.
AB  - Empty sella syndrome (ESS) is a multicausal entity. The incidence of primary
      empty sella syndrome (PESS) in children with neuroendocrine dysfunction is not
      known. In the pediatric age group, frequency seems to have been underestimated. A
      total of 117 cases of neuroendocrine disorders, including complete growth hormone
      deficiency, primary hypothyroidism with pituitary resistance to thyroid hormone,
      obesity, central precocious puberty, hypothalamic hypogonadism and central
      diabetes insipidus, have been studied with computed tomography and/or magnetic
      resonance imaging of sellar region for etiologic evaluation. Twenty-one patients
      were found to have PESS. We noted a high incidence of PESS in children with
      neuroendocrine dysfunction (17.9%). Children with neuroendocrine dysfunction
      should be investigated with respect to PESS, and children with PESS recognized
      coincidentally should be studied with the particular consideration of subclinical
      neuroendocrine dysfunction.

PMID- 7645386
TI  - Left renal pelvis of male neonates is predisposed to dilatation.
AB  - Dilatation of the renal pelvis has been observed as an ultrasonographic finding
      of ureteral reflux as well as hydronephrosis. However, little information is
      available on the prevalence of renal pelvis at dilatation in neonates. We
      measured the inner pelvis dimension of the kidneys in 511 apparently healthy
      neonates (279 boys and 232 girls) using an ultrasound scanner to determine the
      prevalence of renal pelvis dilatation. Ninety per cent of the neonates had an
      inner dimension of both renal pelvises below 5 mm. The prevalence of left renal
      pelvis dilatation of 5 mm or more was significantly higher in the boys than in
      the girls, 25 (9%) compared to 5 (2%). In contrast, no significant difference was
      found in the prevalence of right renal pelvis dilatation between the sexes. In
      the boys, the prevalence of renal pelvis dilatation of 6 mm or more was
      significantly higher on the left side than on the right. Moreover, the left renal
      pelvis dilatation of the male neonates had a tendency to persist at 1 month of
      age. These findings suggest that the left renal pelvis of the baby boy may be
      predisposed to dilatation.

PMID- 7645387
TI  - Treatment of hyperkalemia in children with intravenous salbutamol.
AB  - The aim of this study is to investigate the efficacy and safety of intravenous
      salbutamol in hyperkalemia. Fourteen children with chronic renal failure, three
      with acute renal failure and hyperkalemia were treated by intravenous infusions
      of 4 micrograms/kg salbutamol. Reductions in the mean plasma potassium (K+)
      concentrations obtained at 40 to 120 min after therapy were statistically
      significant when compared with the mean plasma K+ concentration at the beginning
      of therapy (P < 0.01).

PMID- 7645388
TI  - Effect of valproate and carbamazepine on visual evoked potentials in epileptic
      children.
AB  - The effects of carbamazepine (CBZ) and sodium valproate (SV) monotherapy on
      visual evoked potentials (VEP) were studied in 18 epileptic children receiving
      CBZ and nine epileptic children receiving SV. Pattern reversal VEP were
      determined before the administration of antiepileptic drugs (AED) and 1 year
      later during which time the patients had received AED. The VEP amplitude showed
      no consistent changes after 1 year of CBZ and SV therapy, but VEP P-100 latencies
      were significantly prolonged after 1 year of CBZ therapy. We conclude that CBZ
      causes a slowing down of central impulse conduction and that VEP is useful to
      evaluate the effects of AED within the central nervous system.

PMID- 7645389
TI  - Long-term change of anti-acetylcholine receptor antibody in patients with
      myasthenia gravis after thymectomy.
AB  - Anti-acetylcholine receptor antibody (AChR Ab) plays an important role in the
      pathogenesis of myasthenia gravis (MG). We investigated the change of anti-AChR
      Ab titer after thymectomy of 10 MG patients including five patients whose age at
      onset was younger than 16 years. Anti-AChR Ab titer was increased in four of six
      patients with remission and three of four patients without remission. Change of
      anti-AChR Ab titer in individual patients showed an increase occurred 1-4 years
      after thymectomy. It is likely that thymectomy influences immune response and
      induces autoreactive lymphocytes and autoantibodies.

PMID- 7645390
TI  - Effect of hypocalcemia on muscle in disorders of calcium metabolism.
AB  - We reported on three hypocalcemic patients with various serum creatine kinase
      (CK) levels and Ca metabolic disorders. Two patients with moderate hypocalcemia
      had increased CK levels (hyper-CK-emia), which normalized during treatment for
      the hypocalcemia; a negative correlation between the Ca and CK levels was
      observed in both patients. The remaining patient with mild hypocalcemia had a
      normal CK level. We discuss the effect of hypocalcemia on muscle in our patients
      as well as previously reported patients. Muscle may respond to hypocalcemia in
      three stages, namely homeostatic, asymptomatic hyper-CK-emic and myopathic
      stages.

PMID- 7645391
TI  - Peripheral blood lymphocyte subpopulations in three infants with
      hepatosplenomegaly caused by cytomegalovirus infection.
AB  - Mononucleosis is defined as atypical lymphocyte proliferation which causes
      clinical symptoms such as tonsillitis, lymphadenopathy, or hepatosplenomegaly.
      Mononucleosis syndrome is caused by cytomegalovirus (CMV), Toxoplasma, hepatitis
      virus, adenovirus, or other agents as well as by Epstein-Barr virus. The syndrome
      is immunologically characterized by the proliferation of activated T cells (HLA
      DR+ T cells). We encountered three infants with hepatosplenomegaly who were
      diagnosed as primary CMV infection by the detection of anti-CMV IgM antibody.
      Although the patients were otherwise asymptomatic, analysis of lymphocyte
      subpopulations showed a decreased ratio of CD4+ to CD8+ T cells and augmented
      expression of HLA-DR antigen on T cells characteristic of infectious
      mononucleosis. We conclude that inapparent CMV disease may affect the immunologic
      status of infected children even if it is asymptomatic.

PMID- 7645392
TI  - Measles encephalomyelitis in a patient with a history of vaccination.
AB  - Secondary vaccine failure (SVF) of measles is generally believed to run a milder
      course of illness than an ordinary course of infection. Severe complications such
      as central nervous system involvement have rarely been reported. A 12 year old
      girl, who had received a live attenuated measles vaccine 10 years earlier,
      developed an encephalomyelitis in the absence of symptoms indicative of ordinary
      measles such as Koplik spots. Anti-measles hemagglutination inhibition (HI) titer
      and measles IgM and IgG antibody titers were measured in a commercial laboratory.
      Measles virus genomic sequence was detected by polymerase chain reaction. Both
      serum and cerebrospinal fluid (CSF) samples obtained at acute phase already
      showed extremely high titers of HI (x8192 in serum and x1024 in CSF,
      respectively) and IgG antibody along with the presence of IgM antibody.
      Polymerase chain reaction detected the measles virus genomic sequence in the
      acute phase CSF. The patient's definite history of measles vaccination, high
      titers of HI and IgG antibodies observed at the very early stage of illness and
      the clinical course indicated that this patient has an encephalomyelitis due to
      SVF of measles. It is suggested that measles virus can be a pathogen of
      encephalitis without symptoms indicative of ordinary measles in individuals who
      received live attenuated measles vaccines.

PMID- 7645393
TI  - Serratia marcescens lung abscess in a child with autoimmune neutropenia.
AB  - Though Serratia marcescens is widely known to be the cause of serious infections
      in immunocompromised hosts, a lung abscess caused by S. marcescens is very rare.
      A 5 year old boy who had previously been diagnosed with autoimmune neutropenia
      was admitted because of fever and cough. In spite of treatment with some
      antibiotics, he developed a lung abscess. Aspiration of the pleural fluid
      revealed that S. marcescens was the pathogen of the disease. In the present case,
      there were feasible risk factors for the development of Serratia lung abscess
      namely neutropenia, chronic gingivitis at the time, and treatment with
      cyclosporin A. There are no reported cases of autoimmune neutropenia which
      developed into S. marcescens lung abscess in the literature as far as we can
      determine.

PMID- 7645394
TI  - Acute rheumatic fever and poststreptococcal acute glomerulonephritis caused by T
      serotype 12 Streptococcus.
AB  - We present a rare case of a 10 year old Japanese boy with acute rheumatic fever
      accompanied with poststreptococcal acute glomerulonephritis. We isolated group A
      Streptococcus serotype T 12, a strain that was thought to be nephritogenic but
      not rheumatogenic, from throat culture. Although rare, physicians should be aware
      that acute renal disease may accompany rheumatic fever.

PMID- 7645395
TI  - Successful treatment of retinoic acid syndrome with high-dose dexamethasone pulse
      therapy in a child with acute promyelocytic leukemia treated with ATRA.
AB  - A 5 year old female developed femoral pain, fever, and hemorrhagic tendency. She
      was diagnosed as having acute promyelocytic leukemia (APL). Approximately 2 weeks
      after the administration of all-trans retinoic acid (ATRA), she developed a high
      fever, edema, and respiratory distress which met the criteria for retinoic acid
      syndrome. At first, we tried to treat the patient with oral corticosteroid,
      however, this approach was unsuccessful. Considering the worsening of her
      condition, we then chose to administer a large dose of intravenous dexamethasone
      therapy for 3 days. Immediately after this therapy, she became afebrile,
      respiratory distress and edema disappeared, and there was a general improvement
      of the symptoms. All-trans retinoic acid at the reduced dose of 25 mg/m2, was
      continued for an additional 6 weeks and then discontinued. Since the cessation of
      dexamethasone and ATRA, there has been no relapse of APL in this patient.
      Although based on only one case, we recommend the intravenous high-dose
      dexamethasone pulse therapy (13 mg/m2 per day, for 3 days) for treating retinoic
      acid syndrome which develops in pediatric APL patients treated with ATRA.

PMID- 7645396
TI  - Hemolytic anemia following high-dose intravenous immunoglobulin administration.
AB  - We describe two cases of hemolytic anemia following high-dose intravenous human
      immunoglobulin administration in young females with idiopathic thrombocytopenic
      purpura. Inducement of hemolytic anemia by anti-A and anti-B antibodies in these
      cases necessitates the performance of a minor crossmatching procedure prior to
      immunoglobulin use to prevent the occurrence of this adverse reaction.

PMID- 7645397
TI  - Peripheral expansion of V delta 1-J delta 1/J delta 2+ gamma delta T cells and
      large granular lymphocytes in a patient with Wiskott-Aldrich syndrome.
AB  - A 7 month old Japanese boy was diagnosed to have Wiskott-Aldrich syndrome (WAS)
      because of eczema, thrombocytopenia, progressive immune defect and CD43
      (sialophorin) abnormality. He had developed repeated infections since 16 months
      of age. Gamma delta T cell-receptor positive T cells in the peripheral blood were
      gradually increased from 3.1% (7 months of age) to 5.6% (12 months), 19.6% (18
      months) and 56.7% (25 months). The phenotypes of expanded gamma delta T cells
      were delta TCS1-positive (V delta 1-J delta 1/J delta 2) and CD8 dim-positive.
      The proportion of increased granular lymphocytes correlated well with that of
      gamma delta T cells. The significance of peripheral expansion of gamma delta T
      cells and granular lymphocytes in WAS is discussed.

PMID- 7645398
TI  - Neonatal alloimmune thrombocytopenia involving HPA-5b (Br(a)): a rare Japanese
      case.
AB  - Neonatal alloimmune thrombocytopenia (NAIT) is caused by platelet antigen
      incompatibility between the mother and fetus. The frequency of NAIT varies among
      ethnic groups. In Caucasians, HPA-5b (Br(a)) is the antigen that is second most
      frequently implicated. In Japan, NAIT due to anti-HPA-5b antibody is quite rare.
      The present case is the second case of Br(a)-NAIT in Japanese and the first case
      serologically confirmed by monoclonal antibody-specific immobilization of
      platelet antigens.

PMID- 7645399
TI  - Paroxysmal kinesigenic choreoathetosis associated with prenatal brain damage.
AB  - We describe a 15 year old patient with paroxysmal kinesigenic choreoathetosis.
      Neurological examinations revealed a paresis of the right arm and hand that was
      similar to ulnar nerve palsy, a right homonymous hemianopsia and an ocular
      movement disturbance of smooth pursuit to left. Attacks of dystonic spasms began
      abruptly, usually following running, and lasted less than 5 min. Magnetic
      resonance imaging displayed a linear area of increased signal in the T2-weighted
      images along the lateral margin to the left putamen, atrophies of the frontal and
      temporal opercula and a large porencephalic cyst in the left parieto-temporo
      occipital region. A cerebral blood flow study with single photon emission
      computed tomography showed hypoperfusion of the lenticular nucleus and the
      regions corresponding to the atrophies and the porencephalic cyst.
      Electroencephalograms during the attacks could not demonstrate epileptic
      abnormality. Only the neuronal plasticity of an immature brain could explain the
      discrepancy between the observed huge lesions of the brain and the minor
      neurological symptoms present. Attacks of paroxysmal kinesigenic choreoathetosis
      might occur when the basal ganglia maturate to some extent, even if the lesions
      in the brain were caused before birth.

PMID- 7645400
TI  - A boy with atrophic thyroiditis of prepubertal onset, who was positive for TSH
      binding inhibitor immunoglobulins.
AB  - A 12 year old boy was admitted to our hospital because of short stature. From the
      age of 7, his growth velocity decreased and he manifested intolerance to low
      temperatures, hoarseness, dry skin, and slowness of thought and physical
      movement. On admission, his height was 129.8 cm (-3 s.d.) and his body weight was
      43.2 kg (-0.5 s.d.). His clinical features also included relaxation phase of
      tendon reflexes, periorbital puffiness and cold skin but no struma. His bone age
      was 9 years. His serum thyroxine (T4), triiodothyronine (T3), free T4 and free T3
      were low, while his thyrotropin was high. He was positive for antithyroglobulin
      antibodies, antimicrosomal antibodies, and TSH-binding inhibitor immunoglobulins.
      He was diagnosed as having atrophic thyroiditis. We also determined the HLA
      haplotypes of his family members. His father's HLA haplotypes were A2, BW61(a)
      and A24, BW52(b), while his mother's haplotypes were A24, BW52(c) and A30,
      BW60(d). The HLA haplotypes of both the patient and his younger brother showed a
      and d, while the patient's elder brother's HLA haplotypes showed b and c. His
      family members all had normal thyroid function, but his father was positive for
      antimicrosomal antibodies. In summary, we describe a rare case where the onset of
      hypothyroidism was prepubertal, where the pathogenesis may have involved TSH
      receptor blocking antibodies, and where the inheritance of the disease may have
      been from the paternal side of the family.

PMID- 7645401
TI  - Persistent chorea following cardiac surgery for congenital heart disease.
AB  - We describe a 6 year old girl with chorea following cardiac surgery, the first
      such report in Japan. The radical operation for total anomalous pulmonary venous
      return was carried out at the age of 11 months under hypothermia. Seven days
      after the operation, a sudden onset of irritability, dysphagia, chorea,
      generalized, hypotonia, and complete external ophthalmoplegia were seen. These
      symptoms diminished gradually, but chorea remained. We speculated that the cause
      of chorea arose from the cardiac surgery under hypothermia. It is necessary to
      consider 'cardiac surgery' as one of the triggers of certain movement disorders
      including chorea. We tried treatment with haloperidol, pimozide, and several
      other drugs; only pimozide was effective in decreasing chorea without any side
      effects.

PMID- 7645402
TI  - Seroepidemiology of adenovirus type 11 in Fukuoka, Japan.

PMID- 7645404
TI  - HLA-system and the frequency of relapses in childhood minimal change nephrotic
      syndrome in Turkish children.

PMID- 7645403
TI  - CT screening for unrecognized coronary sequel of Kawasaki disease.

PMID- 7645405
TI  - Effect of dopamine receptor blockade on the renal excretory response to acute
      volume expansion (AVE) in conscious Brattleboro rats.
AB  - All the studies were performed on chronically cannulated, conscious Brattleboro
      rats, housed in metabolic cages under standard conditions. The renal excretory
      indices: diuresis (V), sodium (UNa.V), potassium (UK.V), chloride (UCl.V) and
      osmotic (Uosm.V) excretion were measured under the following experimental
      protocol: (1) controls, (2) 2% volume expansion (AVE)-0.9% NaCl i.v. for 2 min,
      (3) Dopamine (DA) receptor antagonist Flupentixol (FLU) 0.5 mg.kg-1 i.v., and (4)
      AVE 10 min after i.v. application of FLU. All the indices studied, given as
      cumulative curves, showed a firm linearity with time during the whole
      experimental period (5 h) in groups 1 and 2 (p < 0.05), while such a relationship
      was not found significantly in groups 3 and 4. AVE quickly, strongly and
      significantly (p < 0.01) increased V and especially UNa.V, UCl.V and Uosm.V.
      Pretreatment with FLU potently suppressed the effect of AVE on the renal
      excretion. FLU alone decreased almost equally V and saliuresis. IN CONCLUSION:
      the DA antagonist FLU blocks the diuretic and saliuretic response to AVE probably
      by affecting tubular processes.

PMID- 7645406
TI  - Interrelation between the renal sympathetic nerve and atrial natriuretic peptide
      in conscious long Evans rats subjected to sodium restriction.
AB  - The renal excretory function and plasma renin activity (PRA) were studied in
      conscious rats on a low sodium diet (25 mmol/kg) after atrial natriuretic peptide
      (ANP) infusion (100 ng/kg b.w./min) for 80 min through a catheter implanted in
      the right atrium. The half of the animals were with bilateral kidney denervation.
      The rats were housed every day from 8 a.m. to 2 p.m. in individual metabolic
      cages for urine collection and Na, Cl, osmolality and endogenous creatinine
      determination. At the last day of the experiments after the ANP infusion, blood
      was taken from the heart for electrolytes, endogenous creatinine and PRA. The
      effect of denervation was monitored by measuring of noradrenaline in kidney
      homogenate. The data indicated that even at low sodium diet ANP stimulates the
      diuresis and sodium excretion without changing the glomerular filtration rate
      (GFR). The kidney denervation combined with ANP infusion increased twice the
      diuresis and four times sodium excretion vs. the control animals. In the same
      time PRA was decreased by about 70%. We assume that the low sodium diet
      attenuates the effect of ANP in respect to the excretory function. This
      inhibitory effect is amplified by the renal sympathetic nerves. The decrease of
      PRA and possibly the increased activity of renal receptors after the denervation
      could explain the data obtained.

PMID- 7645407
TI  - Tissue distribution of polybutylcyanoacrylate nanoparticles loaded with spin
      labelled nitrosourea in Lewis lung carcinoma-bearing mice.
AB  - The tissue distribution of polybutylcyanoacrylate nanoparticles (PBCN) with a
      diameter of 127 nm, loaded with 1-(2-chloroethyl)-3-(1-oxyl-2,2,6,6
      tetramethylpiperidinyl)-1- nitrosourea (spin-labelled nitrosourea, SLCNU) is
      described. PBCN-suspensions were intraperitoneally (i.p.) injected into Lewis
      lung carcinoma bearing mice. The biodistribution of PBCN in the visceral organs,
      blood and tumor was studied by electron spin resonance (ESR) spectroscopy. A
      relatively low accumulation of nanoparticles in the liver and spleen was found.
      The accumulation was negligible in the i.m. implanted primary tumor. SLCNU-loaded
      nanoparticles were mainly found in the lungs, kidneys, and heart. The highest
      content of the particles studied was observed in the lungs of tumor bearing
      experimental animals damaged by metastases. These findings suggest that PBCN
      offer some opportunities in the targeting of SLCNU to lung metastases.

PMID- 7645408
TI  - Effects of agonists and antagonists of some serotonin-receptor subtypes on memory
      and their modulation by the 5-HT-uptake inhibitor fluoxetine.
AB  - The memory effects of agonists and antagonists of some serotonin (5-HT)-receptor
      subtypes were studied in experiments on rats using the method for passive
      avoidance with punishment reinforcement (step-down). The 5-HT1A-receptor agonist
      buspirone (1 mg/kg i.p.) elicited behavioural responses which suggested the lack
      of pronounced effect on learning and retention; the 5-HT1A-receptor antagonists
      NAN-190 (1 mg/kg i.p.) and pindolol (6 mg/kg i.p.) impaired retention tested 24
      hours and 7 days after training as compared to controls. The 5-HT2-receptor
      antagonist ritanserin (1 mg/kg i.p.) impaired retention tested 24 hours and 7
      days after training as compared to controls, while the 5-HT3-receptor antagonist
      ondansetron (0.1 mg/kg i.p.) improved it. The 5-HT1/5-HT2-receptor antagonist
      dotarizine (50 mg/kg orally), characterized by a calcium-antagonistic action,
      too, exerted some facilitating effect on learning. Most of the effects of the 5
      HT-receptor agonists and antagonists were changed when the 5-HT concentration in
      the synaptic region was increased by the 5-HT-uptake inhibitor fluoxetine (20
      mg/kg orally). The results suggest different participation of 5-HT1A-, 5-HT2- and
      5-HT3-receptors in the mechanisms of memory process and its modulation by the
      serotonin level in the cerebral serotonergic synapses.

PMID- 7645409
TI  - Location of the electrical center of ventricular depolarization in rabbits.
AB  - This is a study on the location of the ventricular depolarization center, carried
      out on fifteen healthy rabbits according to the method of Ritsema van Eck. It is
      established that the level of equivalent heart dipole coincides with the fourth
      or fifth intercostal space, but in some laboratory animals this level displays a
      lower positioning. The inference is reached that to secure correct application of
      Frank's lead system it is necessary to use a prompt and precision method for
      determination of the level in question in each individual case. Such a method has
      not been developed as yet. For the time being, the optimal solution of the
      problem could be accomplished through a lead system that is less sensitive to
      electrode positioning errors.

PMID- 7645411
TI  - Signal processing during and across saccades.
AB  - Visual perceptual processing has been found to occur exclusively during fixations
      of the eye (Sanders and Houtmans, 1985; Sanders and Rath, 1991). Does fixation
      time also reflect postperceptual processes such as target classification and
      response selection as well, or can these processes continue during a saccade? In
      a series of experiments on this question two signals were presented at an angular
      distance of 100 degrees. At the start of a trial subjects fixated the left signal
      (S1), which was always a letter that did or did not belong to a predefined target
      set of variable size. Then they moved to the right signal (S2) which indicated
      the mapping of target and no target responses onto the response keys. Subjects
      were capable of starting the saccade upon identification of S1, so that target
      classification of S1 might occur either during the saccade or while fixating S2.
      Although the duration of the saccade was long enough to complete target
      classification, the effect of set size was still partially reflected in the
      fixation duration of S2. This could either be due to incomplete processing during
      the saccade or to interference while integrating S1 and S2. The results of two
      additional conditions were in support of the latter hypothesis, since they showed
      similar effects while no saccade was involved. Subsequent experiments confirmed
      the conclusion that target classification can continue during a saccade. The
      final experiment showed that response selection can continue during a saccade as
      well: The effect of S-R compatibility was reduced in case of a small saccade (8
      degrees) and disappeared altogether when a large saccade was carried out (100
      degrees).

PMID- 7645410
TI  - Disorders of ventricular contractility and electrogenesis in the early stage of
      endotoxin shocked rabbits.
AB  - This is a report on ventricular contractility and electrogenesis disorders in
      rabbits, following intravenous injection of E. coli endotoxin at a dose of 2
      mg.kg-1. At the 30th min, the right ventricular contractility indices
      (dP/dtmax)/P and [(dP/dt)/P]max had lower values, whereas end diastolic pressure
      (EDP), right ventricular systolic pressure (RVSP) and P(dP/dtmax) showed higher
      values compared to the initial ones. Most of the left ventricular contractility
      indices tested showed significantly lower values at the 30th and 60th min of the
      registration. In the scalar orthogonal ECG leads, at the 5th min an increased Qz
      amplitude, and at the 60th min an increased Rz amplitude, a decreased Ry
      amplitude, and QRS complex widening and bradicardia, were registered. In the
      spatial magnitude curve an increased amplitude of the main vectors of ventricular
      depolarization was documented. The changes in electrogenesis are interpreted
      first and foremost by the presence of hemodynamic disorders. The inference is
      reached that both left and right ventricular dysfunction have been already formed
      during the initial stage of endotoxin shock.

PMID- 7645412
TI  - Stimulus preprocessing and response selection in depression: a reaction time
      study.
AB  - Depressed subjects are slower than normal controls in reaction time (RT) tasks.
      However, it is not clear whether depression affects all stages of information
      processing or only some of them. In the present study, this question was
      addressed by using the additive factor method. Ten inpatients and ten control
      subjects performed a two-choice visual RT task. Stimulus intensity and stimulus
      response compatibility were manipulated. The effect of intensity was similar in
      both groups whereas the effect of compatibility was larger for the patients than
      for the controls. This suggests that stimulus preprocessing is unaffected by
      depression whilst response selection is impaired.

PMID- 7645413
TI  - [Applicability of the Spanish version of the Belloc's Physical Status Inquiry
      PSI: a perceived health status measurement scale].
AB  - The objective of this work is to present the adaptation into Spanish of the
      Belloc's Physical Status Inventory-PSI-, and to describe the results of the
      preliminary validity of the Spanish version of this instrument. The process of
      translation and back-translation of the PSI revealed a high linguistic
      compatibility of the English and Spanish versions of the instrument. The
      construct validity was verified, on the same patients, by comparison of the PSI's
      data with the diagnostic categories and the presence of chronicity reported by
      the primary care practitioner, with the mental health status established by the
      GHQ-28, and with the utilization of health resources. We could say dat, in
      general, the PSI is a reliable measure of health status, being especially useful
      for its application on the general population and in patients in contact with
      medical agencies. It is thus justifiable to continue analyzing, by means of more
      specific methodological designs, the performance of this instrument in different
      Spanish populations.

PMID- 7645414
TI  - [Psychosocial factors and adaptation mechanisms in stressful events].
AB  - The relationship between life events and the presence of mental disease has
      received a considerable attention. In this association plays an important role
      the individual vulnerability, that reflects personal factors that predispose to
      the development of psychopathology. Hereditary, psychological, social and
      cultural components have been included in the broad concept of vulnerability.
      Recently the coping behaviour has also been evaluated from this point of view. It
      reflects the strategies that people uses to confront the life events. The role of
      coping behaviour and psychosocial factors in the adaptation to stress are herein
      reviewed.

PMID- 7645415
TI  - [Variation of the demand in the emergency of the Psychiatric Hospital of Madrid].
AB  - The present study investigate several socio-demographics, clinical and
      therapeutics factors that converge in the emergencies of the Psychiatric Hospital
      of Madrid on June, 1989 and 1990. Also, the study approach the changes about the
      demand of attendance, experienced by these emergencies during the period 1979
      1990, related to the introduction of a sectorized care organization through the
      comparison with similar studies realize in the same Hospital. Is studied the
      function of these changes in the progressive reordering of the population demand.

PMID- 7645416
TI  - [Clinical study of four cases of Rett Syndrome].
AB  - Rett Syndrome was first described in 1966 by Andreas Rett. The disorder is
      characterized by a progressive loss of cognitive and motor skills as well as
      development o stereotyped hand movements, occurring after an apparently normal
      development. Authors present three typical cases, and, another one atypical,
      being all of them female. This study takes into account ten different areas about
      chronology, age and reasons in the first consultation, some milestones of
      psychomotor development, the diagnostic criteria--according to Rett Syndrome
      Diagnostic Criteria Work Group (R.S.D.C.W.G.), they consists of necessary,
      supportive and exclusion criteria-, some signs and symptoms that authors consider
      frequently associated with Rett syndrome, some diagnostic tests with
      neurophysiologic technics--E.E.G.--, as well as neuroimagins technics--C.T. and
      M.R.I.--; routine laboratory studies, development scales and something else, the
      DAS-SV scale which is usually used to study different handicaps and therapeutic
      interventions such as: psychosocial, clinical, pharmacological (valproic acid,
      carbamacepine, clorpromacine, etc.) and institutional. Three tables and 72
      bibliographic notes are included.

PMID- 7645417
TI  - [On the aesthetical evidence in the psychotherapeutic meeting].
AB  - The therapeutic function of visual ideas and imaginations is focussed.
      Reminiscences, dreams and fantasies are not only understood as indications of an
      underlying truth, which is to be explored. They have an own truth content, which
      is esthetic. Their creation in the psychotherapeutic encounter unfolds curative
      affects, beyond analytic exploration of psychodynamic reasons.

PMID- 7645418
TI  - [Management in terms of objectives in mental health: a possible and necessary
      process].

PMID- 7645419
TI  - [The international context of mental health].

PMID- 7645421
TI  - Diet and Cancer: Molecular Mechanisms of Interaction. Conference proceedings.
      Washington, D.C., September 1-2, 1994.

PMID- 7645420
TI  - Use of vitamins A and D in chemoprevention and therapy of cancer: control of
      nuclear receptor expression and function. Vitamins, cancer and receptors.
AB  - Vitamin A is metabolized to several biologically active compounds, the best known
      of which is retinoic acid. This compound has been shown to inhibit the growth of
      a variety of tumor cells and to induce a more differentiated phenotype in several
      tumor types. Vitamin D is metabolized to the active compound 1,25
      dihydroxyvitamin D3. This vitamin is well-known for its role in maintaining
      calcium homeostasis in the body. Recently it has been shown that vitamin D3 can
      also inhibit tumor cell replication and stimulate differentiation of selected
      tumor types. Retinoic acid is being used clinically to treat promyelocytic
      leukemia, head and neck tumors as well as cervical dysplasia. Use of vitamin D3
      clinically has been restricted by its affect on calcium metabolism. Recently,
      however, new analogs of vitamin D3 have been developed which have much less
      calcium mobilizing activity, yet still retain their tumor inhibitory properties.
      The action of both of these vitamins is mediated by nuclear receptors which have
      the same structure as steroid receptors. There are three nuclear retinoic acid
      receptors (RAR alpha, beta, and gamma), but only one vitamin D3 nuclear receptor.
      These receptors are expressed in very small amounts. Since the ligand should be
      in vast excess of receptor (ie not limiting), we explored the possibility that
      response to vitamin A might be mediated by control of RAR expression. Using B16
      mouse melanoma cells as a model system, we found that RAR alpha and gamma mRNAs
      were constitutively expressed. RAR beta mRNA was induced by treatment of the
      cells with RA. Induction of RAR beta mRNA occurred within 1h and was not
      inhibited by cycloheximide. The mRNA for all three RARs was dramatically
      decreased with 8-bromo-cyclic AMP treatment and could not be rescued by addition
      of RA. Analysis of RAR gamma revealed that this decrease occurred within 1h of
      exposure to 8-bromo-cyclic AMP and was not blocked by simultaneous treatment with
      cycloheximide. Nuclear extracts from cyclic AMP-treated cells showed a large
      decrease in protein binding to a retinoic acid response element (RARE)
      oligonucleotide compared to control cells. This correlated with a marked
      reduction of RA-stimulated RARE-reporter gene activity in transfected cells which
      were treated with cyclic AMP. Pre-treatment of B16 cells with cyclic AMP prior to
      RA addition dramatically reduced induction of PKC alpha, an early marker of RA
      induced cell differentiation. Thus, cyclic AMP can antagonize the physiological
      actions of RA via its ability to inhibit RAR expression.

PMID- 7645422
TI  - Methionine deprivation regulates the translation of functionally-distinct c-Myc
      proteins.
AB  - Numerous studies have demonstrated a critical role for the c-myc gene in the
      control of cellular growth. Alterations of the c-myc gene have been found
      associated with many different types of tumors in several species, including
      humans. The increased synthesis of one of the major forms of c-Myc protein, c-Myc
      1, upon methionine deprivation provides a link between the regulation of
      oncogenes and the nutritional status of the cell. While deregulation or
      overexpression of the other major form, c-Myc 2, has been shown to cause
      tumorigenesis, the synthesis of c-Myc 1 protein is lost in many tumors. This
      suggests that the c-Myc 1 protein is necessary to keep the c-Myc 2 protein "in
      check" and prevent certain cells from becoming tumorigenic. Indeed, we have shown
      that overproduction of c-Myc 1 can inhibit cell growth. We have also shown that c
      Myc 1 and 2 proteins have a differential molecular function in the regulation of
      transcription through a new binding site of Myc/Max heterodimers. We have also
      recently identified new translational forms of the c-Myc protein which we term
      delta-c-Myc. These proteins arise from translational initiation at downstream
      start sites which yield N-terminally-truncated c-Myc proteins. Since these
      proteins lack a significant portion of the transactivation domain of c-Myc, they
      behave as dominant-negative inhibitors of the full-length c-Myc 1 and 2 proteins.
      The synthesis of delta-c-Myc proteins is also regulated during cell growth and is
      repressed by methionine deprivation. Therefore, the synthesis of c-Myc 1 and
      delta-c-Myc proteins are reciprocally regulated by methionine availability. We
      have also found some tumor cell lines which synthesize high levels of the delta-c
      Myc proteins. Taken together, our data suggest that c-Myc function is dependent
      on the levels of these different translational forms of c-Myc protein which are
      regulated by the nutritional status of the cell during growth. Numerous reports
      have demonstrated a fundamental and diverse role for the myc gene in cellular
      events, including proliferation, differentiation and apoptosis (Cole 1986;
      Spencer and Groudine 1991; Askew et al. 1991; Evan et al. 1992). This is
      dramatically illustrated by the frequent occurrence of a variety of tumors in
      many species having alterations of myc genes and the transduction of c-myc
      sequences by retroviruses (Spencer and Groudine 1991).4+ Eisenman 1990).(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7645423
TI  - Progressive loss of sensitivity to growth control by retinoic acid and
      transforming growth factor-beta at late stages of human papillomavirus type 16
      initiated transformation of human keratinocytes.
AB  - Retinoids (vitamin A and its natural and synthetic derivatives) have shown
      potential as chemopreventive agents, and diets poor in vitamin A and/or its
      precursor beta-carotene have been linked to an increased risk of cancer at
      several sites including the cervix. Human papillomavirus (HPV) plays an important
      role in the etiology of cervical cancer. We have developed an in vitro model of
      cancer progression using human keratinocytes (HKc) immortalized by HPV16 DNA
      (HKc/HPV16). Although immortal, early passage HKc/HPV16, like normal HKc, require
      epidermal growth factor (EGF) and bovine pituitary extract (BPE) for
      proliferation and undergo terminal differentiation in response to serum and
      calcium. However, following prolonged culture, growth factor independent
      HKc/HPV16 lines that no longer require EGF and BPE can be selected (HKc/GFI).
      Further selection of HKc/GFI produces lines that are resistant to serum- and
      calcium- induced terminal differentiation (HKc/DR). HKc/DR, but not early passage
      HKc/HPV16, are susceptible to malignant conversion following transfection with
      viral Harvey ras or Herpes simplex virus type II DNA. We have investigated the
      sensitivity of low to high passage HKc/HPV16 and HKc/GFI to growth control by all
      trans-retinoic acid (RA, an active metabolite of vitamin A). Early passage
      HKc/HPV16 are very sensitive to growth inhibition by RA, and in these cells RA
      decreases the expression of the HPV16 oncogenes E6 and E7. However, as the cells
      progress in culture they lose their sensitivity to RA. Growth inhibition by RA
      may be mediated through the cytokine transforming growth factor-beta (TGF-beta),
      a potent inhibitor of epithelial cell proliferation. RA treatment of HKc/HPV16
      and HKc/GFI results in a dose-and time-dependent induction (maximal of 3-fold) in
      secreted levels of TGF-beta. Also, Northern blot analysis of mRNA isolated from
      HKc/HPV16 demonstrated that RA treatment induced TGF-beta 1 and TGF-beta 2
      expression about 3- and 50-fold, respectively. We next studied the effect of TGF
      beta 1 and TGF-beta 2 on the proliferation of early to late passage HKc/HPVa6,
      HKc/GFI and HKc/DR. While early passage HKc/HPV16 were as sensitive as normal HKc
      to growth inhibition by TGF-beta 1 and TGF-beta 2, the cells became increasingly
      resistant to TGF-beta during in vitro progression, with the proliferation of
      HKc/DR being virtually unaffected by TGF-beta 1 or TGF-beta 2 treatment. Overall,
      loss of growth inhibition by RA parallels loss of TGF-beta sensitivity.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7645425
TI  - Fish oil and cell proliferation kinetics in a mammary carcinoma tumor model.
AB  - In vivo bromodeoxyuridine (BrdUrd) labelling and bivariate BrdUrd/DNA analysis
      was used to evaluate cell cycle kinetics in a rat tumor model known to be
      sensitive to dietary fatty acid manipulation. Fish oil supplementation
      significantly reduced the rate of BrdUrd movement relative to DNA content,
      indicating prolongation of the DNA replication time. This finding, which
      accounted for most of the decrease in tumor growth rate in the fish oil-fed
      group, represents the first description of an alteration in S phase duration by
      an extrinsic factor. The significance of this finding is discussed in relation to
      current understanding of cell cycle regulation. Fish oil feeding is associated
      with slower growth rate in certain tumors (1,2). According to current concepts of
      cellular proliferation (3), regulation of growth by extrinsic factors is thought
      to precede the S phase. This statement is based on the notion that, within a
      given cell type, DNA replication time (S phase duration) is constant (4-6).
      Extensive evidence also supports an on/off mechanism of cell cycle regulation at
      the level of entry into the S phase (3). In this report, we present evidence
      showing, for the first time, that the S phase duration of fat-responsive tumor
      cells can be altered by dietary manipulation of fatty acids. Furthermore, these
      differences in S phase duration appear to account for all the in vivo variation
      in tumor growth resulting from fish oil feeding. Although the mechanism of this
      phenomenon remains unclear, our observations support increasing evidence for a
      regulatory step at the level of the nucleus. They are also important for
      understanding the relationship between dietary fat and tumor growth.

PMID- 7645424
TI  - Short-chain fatty acids and molecular and cellular mechanisms of colonic cell
      differentiation and transformation.

PMID- 7645426
TI  - Vitamin A chemoprevention of lung cancer. A short-term biomarker study.

PMID- 7645427
TI  - Role of apoptosis in the growth inhibitory effects of vitamin D in MCF-7 cells.

PMID- 7645429
TI  - Choline and hepatocarcinogenesis in the rat.
AB  - Rats fed a choline deficient diet develop foci of enzyme-altered hepatocytes with
      subsequent formation of hepatic tumors. This is the only nutritional deficiency
      that, in itself, causes cancer. We suggested that carcinogenesis is triggered, in
      part, because of abnormalities in cell signals which regulate cell proliferation
      and cell death. Because choline deficient rats develop fatty liver (choline is
      needed for hepatic secretion of certain lipoproteins), we examined whether an
      important lipid second messenger involved in proliferative signaling, 1,2-sn
      diacylglycerol, accumulated in liver and resulted in the prolonged activation of
      protein kinase C. We observed that 1,2-sn-diacylglycerol accumulated in the
      plasma membrane from the non-tumor portion of livers of rats fed a choline
      deficient diet, and that unsaturated free fatty acids, another activator of
      protein kinase C, also accumulated in deficient livers. Protein kinase C in the
      hepatic plasma membrane and nucleus of choline deficient rats was elevated for
      months; this is the only model system which exhibits such prolonged activation of
      protein kinase C. Premalignant, abnormal hepatic foci were detected only in the
      deficient rats, and 15% of deficient rats (none of the controls) had
      hepatocellular carcinoma at 1 year on the diet. In rats, an early event in
      choline deficiency is an increase in the rate of cell death. In liver from
      choline deficient rats, we observed an increase in the numbers of liver cells
      with fragmented DNA (characteristic of programmed cell death; apoptosis). We used
      a cell culture model (immortalized rat hepatocytes) to study the effects of
      choline deficiency on apoptosis. Liver cells grown in a choline deficient medium
      became depleted of choline, accumulated triacylglycerol and 1,2-sn
      diacylglycerol, and had increased DNA fragmentation and other morphologic and
      biochemical changes associated with apoptosis. This model has great potential as
      a tool for studying the underlying link between choline deficiency and the
      regulation of the balance between cell proliferation and cell death. We suggest
      that choline deficiency altered the cell proliferation signals mediated by
      protein kinase C within liver, and altered cell apoptosis. These changes in cell
      signaling may be the triggering events which result in hepatic carcinogenesis.

PMID- 7645428
TI  - Vitamin D and prostate cancer.
AB  - Our findings demonstrate the presence of VDR in various human prostate cancer
      cell lines and in primary cultures derived from normal, BPH and prostate cancer.
      In addition, 1,25-D induced several bioresponses in these cells including growth
      inhibition and PSA stimulation. Based on examples in many different malignant
      cells as well as our data in prostate cells, that vitamin D is anti-proliferative
      and promotes cellular maturation, it seem clear that vitamin D must be viewed as
      an important cellular modulator of growth and differentiation if addition to its
      classical role as regulator of calcium homeostasis. In this respect, vitamin D
      has the potential to have beneficial actions on various malignancies including
      prostate cancer. Its ultimate role in prostate cancer remains to be determined,
      but 1,25-D may prove useful in chemoprevention and/or differentiation therapy. We
      believe the data currently available provide the basis for an optimistic view on
      the possible use of vitamin D to treat prostate cancer in patients and that
      further investigation is clearly warranted to better define its potential
      therapeutic utility.

PMID- 7645430
TI  - Dietary effects on gene expression in mammary tumorigenesis.
AB  - Studies were undertaken to determine the effect a high fat diet has on the
      hormonally controlled transcription of the Mtv-1 locus in C3Hf mice. The
      expression of this locus in the initiating event in mammary tumor development in
      the C3Hf mouse. Mice were weaned at 21 days to either a high fat diet containing
      23.5 percent corn oil or to a low fat diet containing 5 percent corn oil. Mice
      were sacrificed at first, second, and third parity, or when they had developed
      mammary tumors, and their mammary glands and mammary tumors were isolated. RNA
      was isolated from all mammary glands and breast tumors and analyzed. The high fat
      diet accelerated the transcription of the Mtv-1 locus. The transcripts of this
      locus, which are never seen in C3Hf mouse mammary glands until second parity,
      were present in first parity mammary glands of 6 out of 10 high fat diet C3Hf
      mice which were studied. The mammary glands of 15 first parity C3Hf mice which
      were on the low fat diet were analyzed and none contained the Mtv-1 specific
      transcripts. In addition, mammary tumor development was detected earlier (11 vs
      17.8 months) and after fewer litters (2.1 vs. 4.2) on the average in high fat
      diet C3Hf mice. One C3Hf mouse on the high fat diet developed a breast tumor at
      six months without going through pregnancy. These results indicate that a high
      fat diet of 23.5 percent corn oil can accelerate hormonally controlled gene
      expression specifically linked to mammary tumorigenesis.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7645431
TI  - Effect of dietary fatty acids on gene expression in breast cells.

PMID- 7645432
TI  - Lipotrope deficiency and persistent changes in DNA methylation. Lipotrope
      deficiency and DNA methylation.

PMID- 7645433
TI  - 'Elder abuse': the case for greater involvement of geriatricians.

PMID- 7645434
TI  - The compulsory removal of elderly people in England and Wales under Section 47 of
      the National Assistance Act and its 1951 Amendment: a survey of its
      implementation in England and Wales in 1988 and 1989.
AB  - Section 47 of the National Assistance Act 1948 and its 1951 Amendment allow for
      the compulsory removal from their homes of predominantly elderly people to a
      place of safety. The Amendment has been in use for over 40 years. Little
      information is available on the workings of the Acts in England and Wales. For
      the period 1988 to 1989 inclusive, 771 requests for compulsory removal were
      received by 148 'proper officers'. We examined referrals and removals under the
      Acts. During this time 165 people were removed. The majority of referrals were
      from family practitioners (46%), but social workers also played a role (18%). Of
      the 165 people who were actually removed from their homes, 41 were removed under
      Section 47 of the National Assistance Act and 124 under its 1951 Amendment. The
      outcome of compulsory removal was only known in 126 instances. In 34% of cases
      the person was transferred to residential care and 24% returned home; 18% of the
      detainees died during their compulsory admission. The outcome varied
      significantly between health regions (chi 2 = 72; p < 0.001), with for example
      apparently high death rates in the North West, Trent and South West regions. For
      a disturbing 24% of people nothing is known of their fate. A mandatory reporting
      system to examine the use of this legislation is required.

PMID- 7645435
TI  - Cost analysis of fracture of the neck of femur.
AB  - A detailed cost analysis of fractures of the neck of femur in elderly patients
      has been conducted at Aberdeen Royal Infirmary. The aims of this study were as
      follows: (1) to show that the use of average orthopaedic bed day costs can lead
      to an overestimation of costs; (2) to identify the key explanatory variables of
      hip fracture costs; and (3) to identify differences in resource consumption
      between patient groups. The care of 50 first and ten second (contralateral) hip
      fracture patients admitted to Aberdeen Royal Infirmary in 1993 was costed in
      considerable detail. Acute care, convalescence, rehabilitation and operations
      accounted for more than 90% of total costs in both groups. It was found that
      patients who were admitted from their own homes cost significantly more than
      patients who were admitted from long-term care (4018 pounds vs. 2069 pounds; p <
      0.001). In order to validate the costed samples, additional data were collected
      on all hip fracture patients admitted to Aberdeen Royal Infirmary in 1993. The
      main factors in explaining cost variation were the number of days spent in acute
      care and convalescence or rehabilitation [r2 = 0.62; logcost = (0.009 x acute
      days) + (0.01 x rehabilitation days) + 3.213]. Age and place of residence prior
      to admission explained a further 2.8% of total costs but neither variable was
      statistically significant. When costing fractures of the neck of femur, we
      recommend the collection of a minimum data set of these four variables which
      account for 65% of the variation in total costs.

PMID- 7645436
TI  - Inhaler technique of elderly patients: comparison of metered-dose inhalers and
      large volume spacer devices.
AB  - Large volume spacers (LVSs) reduce systemic absorption of steroid from metered
      dose inhalers (MDIs) but there are no data to support the widespread belief that
      LVSs are easy for older people to use. MDI and LVS technique was examined in 40
      inhaler-naive patients [19 men; 70-92 (mean 78.3) years] with chronic airways
      disease and mental test scores > 7/10. On day 1, technique was taught and errors
      corrected if possible. Technique was scored and patients asked which device they
      preferred. They were prescribed the device with which they were most competent.
      Those competent with both were given a device randomly. Technique was reassessed
      on day 29 without further tuition. On day 1 only three patients (8%) had
      inadequate technique for LVS vs. 12 (30%) for MDI (chi 2 = 6.90; p = 0.032). The
      main problems were inability to trigger the device (two patients with both
      devices), problems co-ordinating triggering and inhalation (20 patients with
      MDI), problems inserting the MDI into the LVS (seven patients), and unnecessary
      repetitive firing of the LVS (three patients); 28 (70%) preferred LVSs. On day
      29, 29/30 (97%) with LVSs used them adequately, as did 13/15 (87%) using MDIs
      (five patients used both). LVSs have advantages over MDIs for elderly patients in
      terms of patient preference and inhaler technique.

PMID- 7645437
TI  - The prognostic significance of protein-energy malnutrition in geriatric patients.
AB  - Although it has been shown that protein-energy malnutrition is a predictor of
      adverse outcome in geriatric patients, it is unclear whether this is due to
      underlying disease or disability, or whether malnutrition is an independent
      outcome predictor. To clarify the predictive role of malnutrition, we analysed
      the 4.5-year mortality and living location follow-ups of 219 geriatric patients
      admitted to a geriatric assessment unit. Prevalence of anthropometric and
      serological malnutrition indicators were between 13.7% and 39.8% at hospital
      admission. In bivariate models, prealbumin, subnormal arm muscle area, and
      subnormal body weight were predictors of mortality and survival at home. On the
      other hand, albumin, transferrin, and triceps skin-fold thickness did not predict
      these outcomes. In multivariate models the hazard ratio (HR) of 4.5-year
      mortality remained significant with an HR of 1.8 (95% CI 1.3-2.6) for subnormal
      arm muscle area, and 1.6 (95% CI 1.0-2.6) for subnormal body weight. Prealbumin
      was the strongest serological outcome predictor (multivariate mortality HR 1.9,
      95% CI, 1.3-2.8). In these models, subnormal cognitive function, impaired
      physical function, and creatinine clearance < 30 ml/min were also associated with
      increased mortality. Malnutrition did not predict hospital discharge location,
      but among patients discharged home, those with initial malnutrition had a
      decreased length of survival at home. Our findings indicate that certain protein
      energy malnutrition indicators are independent risk factors predicting decreased
      length of overall survival and survival at home in geriatric patients.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7645438
TI  - Age-related discrimination in the use of fibrinolytic therapy in acute myocardial
      infarction in Norway.
AB  - Age-related use of fibrinolytic therapy in acute myocardial infarction was
      studied for patients admitted to the intensive care unit in four hospitals
      comprising 10% of the national hospital bed capacity in Norway. Altogether, 446
      patients were included. All had validated acute myocardial infarction or acute
      ischaemic coronary heart disease treated with fibrinolytic medication. The
      fibrinolytic treatment rate decreased linearly from 74% among patients younger
      than 50 years to 15% among those older than 80 (p < 0.0001). In a multiple
      logistic regression, low age, short pre-hospital time and no previous myocardial
      infarction strongly predicted use of fibrinolytic therapy (p < 0.0001), and male
      sex was a significant predictor for use of fibrinolytic therapy (p = 0.01).

PMID- 7645439
TI  - Control over future health in old age: characteristics of believers and sceptics.
AB  - In a cross-sectional study of a total population aged 70 years and over in a
      rural New Zealand township (sample size 682) we investigated factors which
      characterize those who felt they had a great deal of control and those who felt
      they had little or no control over future health. In a significant logistic
      regression model those with a feeling of a great deal of control over future
      health had a lower prevalence of chronic obstructive lung disease, higher
      prevalence of diabetes, took less alcohol, were more likely to be satisfied with
      bowel function, had a lower protein intake, were more likely to participate in
      strenuous to moderate activity and were less likely to have features of
      depression. Different perceptions of control were associated with significant
      differences in health practices and health status.

PMID- 7645440
TI  - The levodopa test in Parkinson's disease.
AB  - The clinical diagnosis of Parkinson's disease may be difficult. In elderly
      patients there may be other causes of the triad of rigidity, bradykinesia and
      tremor. This study was designed to assess whether a single levodopa challenge
      could predict dopa responsiveness in patients with Parkinson's disease. Twenty
      two of 27 newly diagnosed patients completed the study. Of the 22, 17 (77%)
      responded positively to the initial test and five (23%) showed no response. At 1
      month, 18 (82%) were improved on treatment and four (18%) were not. Thus the
      initial test predicted 17 (94%) of the 18 who responded at 1 month and correctly
      identified the response of 21 (95%) of the 22 patients. There was only one false
      negative result. Patients with negative results turned out to have other
      parkinsonian syndromes. A positive levodopa test helps to confirm the diagnosis
      of Parkinson's disease and a negative test should alert one to alternative
      diagnoses.

PMID- 7645441
TI  - The relationship between age and cutaneous aryl hydrocarbon hydroxylase (AHH)
      activity.
AB  - Aryl hydrocarbon hydroxylase (AHH), a component of the mixed-function oxygenase
      system, has been identified in liver and in many extrahepatic tissues, including
      the skin. In this study, the effect of ageing on cutaneous AHH activity in both
      male and female Wistar and Brown Norwegian rats of two age groups (average ages
      being 44 and 130 weeks) was assessed using benzo(alpha)pyrene as substrate and by
      measuring the formation of the fluorescent metabolite 3
      hydroxybenzo(alpha)pyrene. Results show that cutaneous metabolism of polycyclic
      aromatic hydrocarbons does not change between young adulthood and senescence in
      either male or female rats. Sex-related differences did occur, however, and may
      be explained, partly, by the existence of different molecular forms of cyt-P450.
      In conclusion, age does not appear to be a major determinant of basal cutaneous
      AHH activity in rats.

PMID- 7645442
TI  - Self-reported tooth loss and bone mineral density in older men and women.
AB  - It has been reported that postmenopausal women with osteoporosis have a higher
      than expected number of dentures and fewer teeth than women without osteoporosis.
      The relationship between self-reported tooth loss and bone mineral density (BMD)
      at the hip and spine in 608 men and 874 women, aged 65-76 years, was examined in
      a cross-sectional study. BMD was measured using dual X-ray absorptiometry. Twenty
      four per cent of men and 27% of women had no natural teeth. There was a
      consistent decrease in BMD with increasing numbers of teeth lost in men. This
      relationship was independent of age, body mass index and smoking habit
      (trochanter r = -0.14, p < 0.0005; Ward's triangle r = -0.1, p < 0.005; and
      lumbar spine r = -0.07, p < 0.05) with between 5% and 9% difference in mean BMD
      at various sites between men who had all their teeth and men who had no teeth.
      There was no significant association between self-reported tooth loss and BMD in
      women. Tooth loss is associated with lower BMD in men; this relationship is less
      consistent in women.

PMID- 7645443
TI  - Reactivating occupational therapy: a method to improve cognitive performance in
      geriatric patients.
AB  - In this prospective treatment study, the effects of two different occupational
      therapy strategies were compared in two samples of long-term geriatric inpatients
      (n = 22 in each group) with slight to moderate dementia according to DSM-III-R.
      Psychometric ratings after 12 weeks and 24 weeks of treatment have demonstrated
      that the application of a reactivating occupational therapy programme in addition
      to functional rehabilitation is significantly more efficient than the application
      of functional rehabilitation alone on levels of cognitive performance,
      psychosocial functioning, and the degree of contentedness with life. These
      results support the assumption that geriatric patients, if stimulated for a
      longer time, are able to mobilize latent resources of cognitive and psychosocial
      performance. Reactivating occupational therapy has a place in the treatment of
      long-term geriatric patients.

PMID- 7645444
TI  - Returning home after acute hospitalization in two French teaching hospitals:
      predictive value of patients' and relatives' wishes.
AB  - Identifying elderly patients who are unable to return home immediately after
      acute hospitalization is difficult. For these patients, early planning of
      discharge might reduce the length of hospitalization. We conducted a cohort study
      to investigate the roles of patients' characteristics and patients' and principal
      carers' wishes about patients returning home in predicting the outcome of
      hospitalization for 510 patients aged 75 years or more admitted to acute medical
      care units via the emergency departments of two teaching hospitals in Paris
      (France). Patients' characteristics and patients' and principal carers' wishes
      were investigated within 24-48 hours of admission. The outcome of hospitalization
      was defined as discharge to home or residential/nursing home. The opposition of
      the principal carer to a patient returning home was the most powerful predictor
      of discharge to a residential/nursing home. Advanced age, living alone,
      disability in Activities of Daily Living, altered mental state and presence of a
      chronic condition fatal within 4 years were also independently associated with
      discharge to a residential/nursing home. The patient's wishes were predictive in
      univariate but not in multivariate analysis. These results suggest that the
      principal carer's wishes about a patient returning home might be taken into
      consideration early in a hospital stay for more effective discharge planning.

PMID- 7645445
TI  - The PAQUID survey and correlates of subclinical hypothyroidism in elderly
      community residents in the southwest of France.
AB  - The aim of this study was to assess the prevalence of increased thyroid
      stimulating hormone (TSH) levels (subclinical or undiagnosed hypothyroidism) in a
      representative sample of a community-living elderly population and to examine the
      relationships with cognitive functions and depressive symptoms. An
      epidemiological study was made of a cohort of 2792 subjects over 65 years of age.
      A blood sample was obtained from 425 volunteers of this cohort and assayed for
      TSH. Every subject participating in the study was interviewed and given a battery
      of neuropsychological tests by a psychologist. Three hundred and eighty-one
      subjects (89.7%) had normal TSH levels; 18 subjects (4.2%) had TSH lower than 0.4
      microU/ml, associated in two of them with hyperthyroxinaemia. Twenty-six subjects
      (6.1%) had increased TSH levels, associated in 18 of them with a normal free
      thyroxine level and in eight with a low free thyroxine level. Increased TSH
      levels were significantly linked with female sex and with the presence of
      symptoms of depression on the CES-D scale but not with impairment of cognitive
      function.

PMID- 7645446
TI  - Variability in scoring the Hachinski Ischaemic Score.
AB  - Multi-infarct dementia (MID) may be the second most common form of dementia in
      later life. A commonly used aid in the clinical diagnosis of MID is the Hachinski
      Ischaemic Score (HIS). The usefulness of this score is controversial, and we
      hypothesized that this is because many items of the HIS are open to a wide range
      of interpretations. We therefore canvassed 45 research and academic centres in
      the United Kingdom and Ireland with an interest in dementia to assess the
      variability of interpretation of the HIS. Five template cases were constructed,
      in which were embedded items which were felt to be potentially contentious. Fifty
      five out of 94 (59%) respondents replied. There was a very wide variation in the
      scores assigned to each vignette. In only five of 65 items was there complete
      agreement among replies: in general there was a very large range for each item.
      Thirty of the items showed less than 90% agreement. The apparent simplicity of
      the HIS conceals possibilities for ambiguous interpretation of individual items.
      This is a property common to many 'simple' rating scales. It should not lead to
      outright rejection of these scales, but rather to a refinement and clarification
      of the scoring and assessment techniques.

PMID- 7645447
TI  - Function of the oxidative metabolism of phagocytes in elderly people:
      relationship to nutritional and inflammatory status.
AB  - The purpose of this study was to investigate the phagocyte production of oxygen
      free radicals (OFR) in the whole blood of elderly patients (EP), by measuring
      chemiluminescence at the basal state and after stimulation, and to study the
      relationships between its impairment, if any, and blood indices of the
      nutritional and inflammatory status in elderly patients with (Inf) and without (N
      Inf) inflammatory diseases. The results showed that OFR production by resting
      circulating phagocytes, assessed by chemiluminescence on whole blood, is markedly
      increased in EP, irrespective of any in vitro stimulation. The significant
      correlation we found between basal chemiluminescence and immunoglobulins levels,
      IgM, IgG and IgA in the whole EP sample, and IgG in the N-Inf group, suggests
      that it could be linked to the cytokine imbalance that favours Th2- and impairs
      Th1-type of cytokine production by T-cells in EP. The basal overproduction of OFR
      was observed both in Inf and N-Inf EP and unexpectedly was less marked in group
      Inf EP. This observation suggests a relative impairment in EP phagocytic adaptive
      responses to inflammatory conditions. This suggestion was confirmed by the
      absence of significant differences between the chemiluminescence index CLI
      calculated after phorbol myrisate acetate (PMA) stimulation in group Inf vs. N
      Inf EP, and by the lower CLI observed in group Inf phagocytes stimulated by
      opsonized zymosan. The role of blood changes associated with inflammation and/or
      nutrition in this relative impairment is supported by the positive correlations
      that we observed between CLI and acute-phase proteins.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7645448
TI  - Arterial oxygen saturation during upper gastrointestinal endoscopy in elderly
      patients: the role of endoscope diameter.
AB  - The effect of endoscope diameter upon arterial oxygen saturation was investigated
      in 52 elderly patients by comparing two groups of 26 patients examined with
      different diameter endoscopes (PQ20 and Q10). In the group of 26 patients
      examined with the larger endoscope (Q10), the baseline oxygen saturation values
      and those during intubation were significantly higher than in the group examined
      with the smaller instrument (PQ20). There was no significant difference in oxygen
      saturation between the two groups after sedation or during the procedure as a
      whole. Our findings suggest that the examination of elderly patients using a
      standard diameter endoscope does not pose any greater risk.

PMID- 7645451
TI  - [Renal cell carcinoma with regional lymph node metastasis].
AB  - A follow up study of 20 cases of renal cell carcinoma with regional lymph node
      metastasis at the department of urology in Niigata Cancer Center Hospital from
      1979 to 1993 is presented. During this period, we treated 249 patients with renal
      cell carcinoma with or without lymph node metastasis. Lymph node metastasis could
      be estimated in 188 out of 249 patients. Histologically, lymph node metastasis
      was classified as pN1 in 8 cases, pN2 in 7 cases, and pN3 in 5 cases. The 3- and
      5-year survival rates of 20 patients with lymph node metastasis were 45.0% and
      16.4%, respectively. Nine of the 20 cases had no distant metastasis and 11 cases
      had distant metastasis. Three of the 9 patients with distant metastasis had no
      recurrence. Two of these 3 patients are still alive after 10 years and 3 years
      and 1 patient died because of acute heart failure. These 3 patients had pN1
      metastasis smaller than 1 cm lymph node. Four of the 11 patients with distant
      metastasis had more than a two-year survival. However, 3 patients died due to
      renal cell carcinoma although primary and metastatic regions were resected and
      IFN with chemotherapy were given. Only one patient is still alive without
      recurrence after 3 years. This case detected as right renal cell carcinoma with
      pN2 metastasis and bilateral pulmonary metastasis was treated with radical
      nephrectomy with regional lymph node dissection and administered Methotrexate,
      VP16 and CisPlatinum chemotherapy and IFN.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7645450
TI  - [The effect of takusha and kagosou on calcium oxalate renal stones in rats].
AB  - We examined the inhibitory effect of the two Kampo medicines, takusha and kagosou
      on the formation of calcium oxalate renal stones induced by ethylene glycol (EG)
      and 1 alpha(OH)D3 (1 alpha-D3) in rats. Wistar strain rats were divided into 4
      groups (A: normal control, B: stone, C: kagosou, D: takusya). There was no
      significant difference in urinary calcium excretion or oxalate excretion between
      the stone group and kampo medicine groups. The calcium content of the kidneys was
      significantly lower in the takusha group than in the other two groups (Stone
      group and kagosou group). Takusha was effective in preventing oxalate stone
      formation in rats. Kagosou, which had strong inhibitory effect on calcium oxalate
      crystal growth and aggregation in vitro as well as takusha, was not effective
      against in vivo calcium oxalate stone formation in rats. These findings suggest
      that takusha prevents the formation of calcium oxalate stone by inhibiting
      calcium oxalate crystal growth and aggregation.

PMID- 7645449
TI  - The Timed Test of Money Counting: a short physical performance test for manual
      dexterity and cognitive capacity.
AB  - The competent handling of money is an essential basis for living independently.
      Seventy-eight consecutively admitted patients to a geriatric hospital underwent
      the Timed Test of Money Counting (TTMC) which measures patients' ability to open
      a purse, take out all the money and count it. Further assessment included Mini
      Mental State Examination (MMSE), Barthel Index of ADL, Self-maintaining and
      Instrumental Activities of Daily Living (IADL), grip strength and Williams' Board
      Test. The TTMC was reliable (inter-rater and intra-rater) and showed construct
      and concurrent validity with other measures of physical function. Unlike many
      other physical performance tests the TTMC is quickly performed and requires no
      special equipment or training.

PMID- 7645452
TI  - [Clinical study of prostatic cancer--statistical analysis of 184 cases in the
      latest 21 years].
AB  - One hundred and eighty-four patients with prostatic cancer were treated at Mie
      University Hospital from 1973 to 1993. They were between 47 and 90 years old,
      with an average age of 71.8 years old. One hundred and fifty-eight patients
      (85.8%) were in either stage C or D. Of the 146 cases histologically examined,
      17.8% were well differentiated adenocarcinoma, and 47.9% and 34.2% were
      moderately and poorly differentiated adenocarcinomas, respectively. The overall 3
      year, 5-year and 10-year survival rate were 64.2%, 44.9% and 24.2%, respectively.
      The patients with high stage and/or poorly differentiated adenocarcinomas
      revealed worse prognosis. Although the prognosis in the patients treated with
      estrogen and orchiectomy was better than that with estrogen alone, there was no
      significant difference between the 2 treatment groups. The prognosis of patients
      with prostatic cancer has been improved since 1988. A possible explanation is
      that prostate specific antigen has been introduced as a tumor marker, which might
      contribute to an accurate diagnosis in prostatic cancer and improve the prognosis
      of the disease. In conclusion, the diagnosis in lower stage and radical
      prostatectomy might bring favorable prognosis. In future, safer and more
      effective chemotherapy and endocrine therapy including LH-RH analogue are
      awaited, to obtain a better prognosis in the patients with advanced prostatic
      cancer.

PMID- 7645454
TI  - [A case of renal cell carcinoma extending into the inferior vena cava in a long
      term hemodialysis patient].
AB  - We report a case of left renal cell carcinoma extending into the inferior vena
      cava associated with the acquired cystic disease of the kidney (ACDK). The
      patient was a 46-year-old man, who had been treated with hemodialysis for 12
      years. In November 1992, ACDK was observed on computed tomography (CT) for
      routine check up, but no tumorous lesions were detected. He noticed bleeding from
      the urethra in May 1994. CT and magnetic resonance imaging (MRI) revealed left
      renal tumor with intrahepatic vena caval tumor thrombus. There were no findings
      of distant metastasis. Left radical nephrectomy and partial removal of vena cava
      were performed. Histopathologically, renal cell carcinoma, pT3b, pN0, stage III
      was diagnosed.

PMID- 7645453
TI  - [Clinical evaluation of a new polymerase chain reaction assay for detection of
      Chlamydia trachomatis in young patients with acute epididymitis].
AB  - Specimens from 15 young patients presenting with acute epididymitis were tested
      for the presence of Chlamydia trachomatis by an enzyme immunoassay (EIA),
      polymerase chain reaction (PCR), and for other bacteria by standard laboratory
      techniques. C. trachomatis urethral infection was detected in 3 patients by an
      EIA test of the urethral swabs (20%) and in 13 patients by the PCR (87%). This
      difference in detection rate was statistically significant (p < 0.005). Thirteen
      specimens were positive by the PCR, but only three of them were positive by the
      EIA method. These findings indicate that the PCR assay is a highly sensitive
      assay for the detection of C. trachomatis in male urine specimens and provides a
      noninvasive technique for routine screening of chlamydia infection in the patient
      with acute epididymitis.

PMID- 7645455
TI  - [Primary squamous cell carcinoma of the ureter: a case report].
AB  - A case of squamous cell carcinoma of ureter is presented. A 64-year-old male
      suffering from right lower abdominal pain and gross hematuria visited our
      hospital. Right hydronephrosis was found by ultrasound examination. Intravenous
      pyelography revealed a right non-functioning kidney. Abdominal computed
      tomographic scanning showed right hydroureteronephrosis and a soft-tissue density
      mass in the right lower ureter. Retrograde pyelography demonstrated a filling
      defect in the right lower ureter. Squamous cell carcinoma was suspected by
      cytological examination. On the basis of the above findings, right
      nephroureterectomy with partial cystectomy was performed. Pathohistological
      diagnosis was squamous cell carcinoma of the ureter, G3, INF gamma, pT3, pR0,
      pL1, pV1, pN1. No evidence of either tumor recurrence or metastasis was found for
      6 months after the operation. Sixty-one cases of primary ureteral squamous cell
      carcinoma, including our case, were collected from the Japanese literature and
      characteristic clinical features of the tumor are discussed.

PMID- 7645456
TI  - [Vesico-uterine fistula after delivery: a case report].
AB  - A case of vesico-uterine fistula which occurred after natural childbirth is
      reported. A 33-year-old woman was admitted in February, 1993, complaining of
      urinary leakage from vagina immediately after natural childbirth. Excretory
      urogram showed an oval shaped extravasation outside the bladder, suggesting that
      the contrast medium went into the luminal space of the uterus. Subsequent
      cystoscopy showed a fistula on the posterior wall, probably the orifice of the
      fistula to the space. As these findings strongly suggested the vesico-uterine
      fistula, surgical operation was done. Rupture of the uterus was observed. Then
      hysterectomy was done because the rupture could not be repaired. Vesico-uterine
      fistula was thought to be the result of the rupture of uterus. Bladder side
      fistula was successfully repaired. Sixty eight cases of vesico-uterine fistula,
      including this case, in the Japanese literature have been reviewed and discussed
      the etiology, symptom and treatment.

PMID- 7645457
TI  - [A case of clear cell adenocarcinoma of the female urethra].
AB  - A case of clear cell adenocarcinoma arising from the female urethra is described.
      Histologically, solid and glandular areas consisted of clear cells. The tumor
      cells were stained positively with antibodies to prostate specific antigen (PSA)
      and prostatic acid phosphatase (PAP), suggesting that the clear cell
      adenocarcinoma arises from the female paraurethral duct, rather than embryonic
      remnant.

PMID- 7645458
TI  - [Complete remission of prostate cancer after LH-RH agonist neoadjuvant therapy: a
      case report].
AB  - We report a case of prostate cancer showing a complete remission after LH-RH
      agonist neoadjuvant therapy. A 69-year-old man was referred to our department
      complaining of pain on urination and urge incontinence. The serum prostate
      specific antigen (PSA) level was 41.6 ng/ml. Needle biopsy specimens from both
      lobes revealed moderately differentiated adenocarcinoma. Chest X-ray, computed
      tomographic (CT) scan, and bone scintigraphy demonstrated neither distant
      metastasis nor local invasion. LH-RH agonist was administered on a monthly basis
      as neoadjuvant therapy. After 4 injections, pelvic lymph node dissection and
      radical prostatectomy were performed on January 11, 1993. Thorough examination
      did not reveal any cancer cells in the removed specimen. The patient was
      discharged 30 days after the operation and has shown no evidence of distant
      metastasis or local recurrence as long as 19 months later.

PMID- 7645459
TI  - [Intrascrotal fibrous pseudotumor accompanied by pelvic kidney with ectopic
      ureteral opening: a case report].
AB  - A case of intrascrotal fibrous pseudotumor accompanied by pelvic kidney with
      ectopic ureteral opening is reported. The patient was a 65-year-old man with the
      complaint of swelling of the right scrotal contents. Ultrasonography showed a
      heterogeneous mass with acoustic shadow from the right epididymis to right
      spermatic cord. Intravenous pyelography revealed a non-visualizing right kidney.
      Endoscopic examination was performed because of the right non-functioning kidney
      and right epididymectomy was performed. Endoscopic findings showed that the
      ureteral opening existed at 6 degrees of the bladder neck. Retrograde pyelography
      demonstrated the right kidney in the pelvic cavity. The tumor was stony hard and
      30 x 50 mm in size. Pathological diagnosis of the tumor was a fibrous
      pseudotumor. We reviewed and discussed 22 cases of fibrous pseudotumor, including
      our case, in the Japanese literature.

PMID- 7645460
TI  - Glen W. Hartman Lecture: American Roentgen Ray Society. Radiology: a century of
      achievement.

PMID- 7645461
TI  - Detection of ureteral calculi in patients with suspected renal colic: value of
      reformatted noncontrast helical CT.
AB  - OBJECTIVE: The purpose of this study was to determine the value of reformatted
      noncontrast helical CT in patients with suspected renal colic. We hoped to
      determine whether this technique might create images acceptable to both
      radiologists and clinicians and replace our current protocol of sonography and
      abdominal plain film. SUBJECTS AND METHODS: Thirty-four consecutive patients with
      signs and symptoms of renal colic were imaged with both noncontrast helical CT
      and a combination of plain film of the abdomen and renal sonography. Reformatting
      of the helical CT data was performed on a workstation to create a variety of
      reformatted displays. The correlative studies were interpreted by separate
      blinded observers. Clinical data, including the presence of hematuria and the
      documentation of stone passage or removal, were recorded. RESULTS: Findings on 18
      CT examinations were interpreted as positive for the presence of ureteral
      calculi; 16 of these cases were determined to be true positives on the basis of
      later-documented passage of a calculus. Thirteen of the 16 cases proved to be
      positive were interpreted as positive for renal calculi using the combination of
      abdominal plain film and renal sonography. The most useful CT reformatting
      technique was curved planar reformatting of the ureters to determine whether a
      ureteral calculus was present. CONCLUSION: In this study, noncontrast helical CT
      was a rapid and accurate method for determining the presence of ureteral calculi
      causing renal colic. The reformatted views produced images similar in appearance
      to excretory urograms, aiding greatly in communicating with clinicians.
      Limitations on the technique include the time and equipment necessary for
      reformatting and the suboptimal quality of reformatted images when little
      retroperitoneal fat is present.

PMID- 7645462
TI  - MR imaging in the diagnosis of intramedullary spinal cord diseases that involve
      specific neural pathways or vascular territories.
AB  - Prior to the advent of MR imaging, the internal architecture of the spinal cord
      could not be directly imaged. The solution of many technical problems (e.g.,
      respiratory motion, cardiac and CSF pulsation, inadequate spatial resolution) has
      provided the opportunity for an increasingly refined analysis of intramedullary
      lesions. This article begins with a brief review of the results of high
      resolution MR imaging studies of the cadaveric spinal cord. The article then
      focuses on MR imaging in the diagnosis of intramedullary diseases that involve
      specific neural pathways or vascular territories. Lesions are categorized as
      degenerative, inflammatory, traumatic, or ischemic. These diseases generally have
      distinctive clinical findings that reflect dysfunction of particular ascending
      sensory tracts or descending motor tracts. The corresponding abnormalities on MR
      images reflect the pathologic changes that occur in the affected neural pathways.
      Knowledge of the appearance of these diseases on MR images allows the formation
      of a narrow differential diagnosis and, in many cases, the confident exclusion of
      neoplasm as the cause of myelopathy.

PMID- 7645463
TI  - Neuroradiology of leukemia.
AB  - Patients with systemic leukemia, especially the acute leukemias, are at an
      increased risk of developing disease of the CNS or head and neck. Such disease
      may take the form of direct leukemic involvement, may result from underlying
      leukemic effects on the immune or hematopoietic systems, or may result from
      antileukemic therapy. This review presents the imaging and clinical features of
      the spectrum of CNS and head and neck disease that may be encountered in patients
      with systemic leukemia. An understanding of the role of radiology in the
      management of these patients is important to the practicing radiologist who is
      confronted with a leukemic patient presenting with signs and symptoms of
      neurologic dysfunction.

PMID- 7645464
TI  - Digital chest imaging with a selenium detector: comparison with conventional
      radiography for visualization of specific anatomic regions of the chest.
AB  - OBJECTIVE: The purpose of this study was to compare a new digital chest
      radiography system that uses amorphous selenium as the X-ray detector with
      conventional radiography for the visualization of various anatomic regions of the
      chest as a first phase of testing image quality. MATERIALS AND METHODS: Six
      observers analyzed pairs of posteroanterior chest radiographs of 40 patients. One
      radiograph in each pair was obtained with a conventional chest film changer, and
      the other was obtained with the digital selenium chest radiography system. Each
      observer rated the visibility and the radiographic quality of 12 different
      anatomic regions. RESULTS: The observers rated visualization obtained with the
      digital system as better than that obtained with the conventional system in four
      regions (right lower lobe, upper lobes, ribs, and soft tissue), as better than or
      equal to that obtained with the conventional system in four regions
      (retrocardiac, retrodiaphragmatic, hilum, and upper mediastinum), and as equal to
      that obtained with the conventional system in four regions (horizontal fissure,
      carina, azygoesophageal recess, and thoracic spine). Some observers had a strong
      preference for the digital images, whereas others showed no preference. The
      conventional system was not ranked high for any region (2880 observations, p <
      .01, sign test). CONCLUSION: The digital selenium chest radiography system
      performs well in a clinical setting, providing visualization of anatomic
      structures that is better than or at least equal to that provided by standard
      screen-film images.

PMID- 7645465
TI  - Helical CT of the upper airway: normal and abnormal findings on three-dimensional
      reconstructed images.
AB  - Imaging of the hypopharynx, larynx, and upper airway are effectively achieved
      with CT and MR imaging. These techniques have proved their diagnostic usefulness
      in assessing the deep soft tissues not visible with laryngoscopy [1]. However,
      with axial imaging, large numbers of images often need to be mentally stacked to
      envision the appearance of the airway. With helical CT, we can create high
      quality three-dimensional (3D) reconstructions [2, 3]. Advantages of helical
      technology include rapid scanning, decreased motion artifact, and minimization of
      misregistration artifacts. Recent work has suggested a role for multiplanar and
      3D reconstructions of helical data for assessing the tracheobronchial tree [3].
      The helically derived 3D models illustrate the normal and abnormal findings
      affecting the airway.

PMID- 7645466
TI  - Bronchial obstruction secondary to aortic pseudoaneurysm: treatment with an
      expandable metallic stent.

PMID- 7645467
TI  - Stereotaxic core biopsy of impalpable spiculated breast masses.
AB  - OBJECTIVE: The role of stereotaxic core biopsy in evaluating mammographically
      detected lesions that have a high probability of being malignant is still
      debated. This study was undertaken to assess the use of stereotaxic core biopsy
      in evaluating spiculated masses, by determining the frequency with which core
      biopsy reduced the number of surgical procedures performed in the management of
      these highly suspicious lesions. MATERIALS AND METHODS: Forty-three impalpable
      spiculated breast masses in 43 patients were sampled with stereotaxic core
      biopsy. All patients underwent surgery. Patient charts were reviewed to determine
      the histopathologic findings at stereotaxic core biopsy and at surgery, and the
      number and type of surgeries performed. RESULTS: Invasive carcinoma was
      identified at stereotaxic core biopsy in 40 (93%) of 43 patients. Therapeutic
      surgical procedures were lumpectomy in 28 patients (22 with axillary dissection)
      and mastectomy in 12. The presence of tumor at the lumpectomy margins led to
      subsequent mastectomy in one case. One lesion yielded atypical ductal hyperplasia
      at core biopsy; surgical biopsy revealed ductal carcinoma in situ. Surgical
      biopsy was recommended in two lesions yielding benign histologies at core biopsy
      and revealed invasive ductal carcinoma in one. Thirty-three (77%) of 43 patients
      had the number of surgical procedures reduced by stereotaxic core biopsy; these
      were patients with carcinoma diagnosed at core biopsy who underwent one-stage
      lumpectomy with axillary lymph node dissection or mastectomy. CONCLUSION:
      Stereotaxic core biopsy reduced the number of surgical procedures in most women
      with impalpable spiculated breast masses. These data suggest that stereotaxic
      core biopsy is a valuable diagnostic technique for assessing these lesions, which
      are likely to represent carcinoma.

PMID- 7645468
TI  - Chronic graft-versus-host disease causing skin thickening on mammograms.

PMID- 7645469
TI  - Association of hiatal hernia and gastroesophageal reflux: correlation between
      presence and size of hiatal hernia and 24-hour pH monitoring of the esophagus.
AB  - OBJECTIVE: The relationship of hiatal hernia to gastroesophageal reflux disease
      remains controversial. Previous endoscopic and radiologic studies of hiatal
      hernia and reflux esophagitis have shown that hiatal hernia is a poor predictor
      of the presence of endoscopic esophagitis, especially for smaller hernias.
      Similar correlations with 24-hr pH monitoring have not been done. The purpose of
      this study was to determine if there is a correlation between the presence and
      size of hiatal hernias and gastroesophageal reflux using 24-hr pH monitoring as a
      measure of the degree of reflux. MATERIALS AND METHODS: We reviewed the barium
      esophagograms and the results of pH monitoring of the esophagus in 319 patients
      (161 women and 158 men; mean age, 51 years). The presence and size of hiatal
      hernia were determined from the radiographic examination; size was categorized as
      "minimal" or "larger" (> or = 2 cm axial length). An abnormal result of pH
      monitoring was defined as a pH less than 4 for 6% or more of the 24-hr
      observation time. RESULTS: Abnormal results of pH monitoring were found in 61
      (31%) of 199 patients with hiatal hernia compared with 21 (18%) of 120 patients
      without hiatal hernia (p < .05). Abnormal findings of pH monitoring were present
      in 33 (35%) of 95 patients with a larger hiatal hernia versus 28 (27%) of 104
      patients with a minimal hiatal hernia (p > .05); a significant difference (p <
      .05) was observed when patients without hiatal hernia were compared with those
      with a larger hiatal hernia. CONCLUSION: Most patients in this study had normal
      results of pH monitoring of the esophagus regardless of the presence or absence
      of hiatal hernia. However, patients with larger hiatal hernias were more likely
      to have abnormal findings on pH monitoring; hiatal hernias of minimal size were a
      poorer predictor of the presence of abnormal gastroesophageal reflux.

PMID- 7645470
TI  - Ether Day.

PMID- 7645471
TI  - Esophageal strictures: findings on barium radiographs.
AB  - An esophageal stricture is a narrowing of the lumen due to inflammation or tumor.
      Lack of distensibility is characteristic of stricture, which may be diffuse or
      localized and which may have abrupt or tapered margins. The purpose of this essay
      is to illustrate the imaging features of various types of strictures, focusing on
      their value in differential diagnosis.

PMID- 7645472
TI  - Anastomotic leaks after low anterior resection for rectal carcinoma: evaluation
      with CT and barium enema.
AB  - OBJECTIVE: After low anterior resection of rectal carcinoma, anastomotic leaks
      are common and may be clinically silent. Radiologic abnormalities related to this
      leakage may be confusing and may persist for years without symptoms. The purpose
      of this study was to evaluate the appearance of these leaks on barium enemas and
      CT scans and to determine their course over time. SUBJECTS AND METHODS: During a
      7-year period, we collected CT scans and barium enemas in 35 patients with
      anastomotic leaks after low anterior resection. A leak was documented by the
      presence of rectal contrast material in an extraluminal collection, endoscopic
      visualization of anastomotic breakdown, or persistence of presacral air longer
      than 6 months after surgery. Twenty patients had examinations in the immediate
      postoperative period and 25 patients had 42 studies in the long-term follow-up
      period (6 months to 10 years). The CT appearance was compared with that in 40
      patients who did not have evidence of leaks after low anterior resection.
      RESULTS: Abnormalities consisted of air-fluid collections in the presacral space,
      extraperitoneal tracking along the iliac vessels, and perirectal anterior
      extension. Collections tended to diminish, but some air and soft-tissue masses
      persisted for months or years (up to 10 years in one case). In 70% of patients
      without leaks, no soft-tissue abnormality was apparent in the presacral space. In
      both groups of patients, the presacral space was widened and the rectum was
      anteriorly located, more so in patients with leaks than in those without. Seven
      patients had recurrent tumor. In the late stages, bulky soft-tissue masses
      obliterated the residual air and soft-tissue abnormality due to the leak.
      CONCLUSION: Radiologists should be aware of the spectrum of findings due to
      anastomotic leaks after low anterior resection and the persistence of presacral
      abnormalities. Delayed symptoms mimic those of recurrence, and radiologic
      findings may be confusing. On some CT scans, it may not be possible to tell the
      difference, but changes due solely to leaks must be included in the differential
      diagnosis.

PMID- 7645473
TI  - Portal vein thrombosis in patients with cirrhosis: does sonographic detection of
      intrathrombus flow allow differentiation of benign and malignant thrombus?
AB  - OBJECTIVE: The objective of our study was to determine if the detection by
      Doppler sonography of blood flow in portal vein thrombi occurring in patients
      with cirrhosis could be used to distinguish benign from malignant portal vein
      thrombi. SUBJECTS AND METHODS: Color and duplex Doppler sonographic examinations
      were performed in 47 patients with proven cirrhosis and portal vein thrombi. The
      examinations were directed at the detection of continuous or pulsatile flow
      within the portal vein thrombi. The nature of the portal vein thrombi was proven
      histologically in 27 patients and by CT findings and clinical history in 20
      patients. The frequency, type, and direction of portal vein thrombus flow was
      evaluated to determine if there was any correlation with the benign or malignant
      nature of the portal vein thrombi. RESULTS: Of the 47 patients, 26 had malignant
      portal vein thrombi and 21 had benign portal vein thrombi. Blood flow was
      detected in 22 of the malignant and in 15 of the benign portal vein thrombi. The
      blood flow was pulsatile in 16 malignant and three benign portal vein thrombi and
      continuous in six malignant and 12 benign portal vein thrombi. The direction of
      the pulsatile flow in the malignant portal vein thrombi was predominantly (13/16)
      hepatofugal. All continuous flow in both benign and malignant portal vein thrombi
      was hepatopetal. The detection of pulsatile flow in portal vein thrombi yielded a
      62% sensitivity and 95% specificity for the diagnosis of malignant portal vein
      thrombus. CONCLUSION: The detection by Doppler sonography of pulsatile flow in
      portal vein thrombi occurring in patients with cirrhosis is a moderately
      sensitive but highly specific sign for the diagnosis of malignant portal vein
      thrombus. However, continuous flow can be detected in benign and malignant portal
      vein thrombus and is thus not useful in differentiating between the two.

PMID- 7645474
TI  - Distinction between benign and malignant adrenal masses: value of T1-weighted
      chemical-shift MR imaging.
AB  - OBJECTIVE: Accuracy of T1-weighted chemical-shift MR imaging for the
      differentiation between benign and malignant adrenal masses was blindly assessed
      among three radiologists. SUBJECTS AND METHODS: MR imaging was performed at 1.5 T
      in 50 patients with 58 adrenal masses, proved benign (n = 38) or malignant (n =
      20) based on surgery or growth (malignant) or stable size (benign) for at least 1
      year. In-phase spin-echo sequences or in-phase breath-hold fast multiplanar
      spoiled gradient-recalled echo (FMPSPGR) sequences with a TE of 4.2 msec were
      compared with opposed-phase breath-hold FMPSPGR sequences with a TR/TE of 35
      155/2.2-2.9 and a 90 degrees flip angle for the detection of lipid in adrenal
      masses. Three radiologists who were blinded to diagnosis and clinical data
      independently rated the likelihood of a benign adrenal lesion on a five-point
      scale of confidence. RESULTS: Mean sensitivity, specificity, and positive
      predictive value for a definite or probable diagnosis of a benign lesion by the
      three readers were 87%, 92%, and 95%, respectively. At the highest (definite)
      confidence of a benign lesion, the mean positive predictive value was 99%, with
      lower sensitivity (54%). Areas under receiver operating characteristic curves for
      the three radiologists were .98 (95% confidence interval [CI] = .94-1.00), .96
      (CI = .91-1.00), and .95 (CI = .89-1.00). Interobserver variation for the
      diagnosis of a benign mass was low (kappa = .79). CONCLUSION: Chemical-shift
      imaging using breath-hold opposed-phase T1-weighted MR images is a reliable and
      reproducible technique for the diagnosis of most benign adrenal masses at the
      highest threshold of confidence.

PMID- 7645475
TI  - Rheumatoid arthritis of the craniocervical region by MR imaging: detection and
      characterization.
AB  - OBJECTIVE: The purpose of our study was to evaluate the potential of contrast
      enhanced MR imaging to detect and to characterize craniocervical rheumatoid
      arthritis in a large population group, to compare MR imaging with clinical and
      conventional radiographic findings, and to examine the relationship between the
      histopathologic and MR imaging findings in seven patients. SUBJECTS AND METHODS:
      We performed contrast-enhanced MR imaging using T2-weighted gradient-echo
      sequences and T1-weighted spin-echo sequences in 136 patients with rheumatoid
      arthritis. Sequential T1-weighted images were obtained before, 3 min after, and
      15 min after injection of contrast material. Plain films were acquired in all
      patients. Serologic status and neurologic status were determined in each patient
      within 2 days of MR imaging. Patients were categorized into one of four groups,
      depending upon whether they had joint effusion, hypervascular pannus,
      hypovascular pannus, or fibrous pannus according to signal patterns on contrast
      enhanced MR images. Signal intensity was measured to assess the enhancement of
      synovial hypertrophy, joint capsule, joint effusion, and the various stages of
      pannus tissue. Histologic specimens were obtained from seven patients and were
      correlated with MR imaging findings. RESULTS: Acute and chronic synovitis were
      differentiated with contrast-enhanced MR imaging as follows: joint effusion (n =
      29), hypervascular pannus (n = 54), hypovascular pannus tissue (n = 8), and
      fibrous pannus (n = 22). Signal intensity differed significantly among the four
      groups on contrast-enhanced T1-weighted images. In 59 patients with effusion or
      hypervascular pannus tissue, atlantoaxial subluxation was diagnosed with plain
      films. Patients with negative findings on radiographic studies (n = 20) had joint
      effusion, hypervascular pannus tissue, hypovascular pannus formation, or fibrous
      pannus tissue on MR imaging studies. Cord compression was found in 10% of all
      cases and isolated sac compression in 16%. Neurologic findings showed no
      correlation with MR imaging features. CONCLUSION: Contrast-enhanced T1-weighted
      spin-echo MR imaging can discriminate between joint effusion and various forms of
      pannus in patients with rheumatoid arthritis of the craniocervical region. MR
      imaging also can detect joint effusion and pannus tissue in patients with
      negative radiographic findings. No relationship between MR imaging findings and
      clinical symptoms were found. Tissue enhancement and histopathologic findings
      correlated in a limited number of autopsies.

PMID- 7645476
TI  - Osteosarcoma and Ewing's sarcoma after neoadjuvant chemotherapy: value of dynamic
      MR imaging in detecting viable tumor before surgery.
AB  - OBJECTIVE: This study analyzed the value of dynamic contrast-enhanced and
      subtraction MR images in detecting residual viable tumor before surgery, with
      emphasis on timing of enhancement, in patients with high-grade osteosarcoma and
      Ewing's sarcoma after neoadjuvant chemotherapy. SUBJECTS AND METHODS: Twenty-one
      patients with proved osteosarcoma or Ewing's sarcoma were treated with
      neoadjuvant chemotherapy followed by surgery. After IV administration of
      gadopentetate dimeglumine, dynamic enhancement patterns on preoperative MR images
      were compared with corresponding areas on histologic sections of the resected
      specimens. On dynamic subtraction images obtained with high temporal resolution
      (1.5-3 sec), the interval between arrival of the bolus of contrast agent in an
      artery and start of tumoral enhancement was used to distinguish residual viable
      tumor. Early enhancing foci (interval artery-tumor < 6 sec) and late or
      nonenhancing areas seen on MR images were correlated with the histopathologic
      findings in these areas of the resected specimens. RESULTS: Early and
      progressively enhancing structures seen on MR images corresponded to feeding
      arteries, physeal vessels, or residual viable tumor at specific preferential
      sites on corresponding histologic sections of the resected specimens. Tumor foci
      as small as 3-5 mm2 could be detected on dynamic MR images. Remnant viable tumor
      was often located subperiosteally and at the margins of the tumor. Occasionally,
      active periosteal reaction without presence of viable tumor contributed to early
      enhancement. Late and gradually enhancing or nonenhancing areas corresponded
      histopathologically to regions of chemotherapy-induced necrosis, mucomyxoid
      degeneration, or fibrosis. Alternatively, late or nonenhancing areas were
      associated with reactive changes such as edema, hemorrhage, or osteomyelitis or
      with tumor-related extracellular matrices such as abundant osteoid or chondroid.
      Viable tumor areas with scarce formation of matrix on microscopy, such as small
      cell osteosarcoma areas or Ewing's sarcoma, showed early enhancement with rapid
      washout of contrast agent on the dynamic MR images. CONCLUSION: Fast dynamic
      contrast-enhanced sequences are essential for identifying residual tumor before
      surgery. A short time interval of less than 6 sec between arterial enhancement
      and tumoral enhancement strongly correlates with presence of viable tumor. Both
      therapy-related alterations of tissue and tumor-related matrices must be
      considered when late or lack of enhancement is noted on dynamic MR images.

PMID- 7645477
TI  - MR imaging of patients with type 1 Gaucher's disease: relationship between bone
      and visceral changes.
AB  - OBJECTIVE: Because treatment is now available for patients with Gaucher's
      disease, methods of follow-up have become important in making treatment
      decisions. Bone abnormalities (infarct and avascular necrosis) tend to be
      irreversible while visceral volumes are not, suggesting that it may be useful to
      follow patients with visceral volume determinations. In order to do so, the
      relationship of one to the other must first be understood. The purpose of this
      paper is to determine the relationships between bone and visceral changes
      identified with MR imaging. MATERIALS AND METHODS: Sixty-two consecutive patients
      from 1 to 78 years old with type 1 Gaucher's disease were studied by MR imaging.
      The examination consisted of two parts: T1-weighted MR images and gradient-echo
      coronal MR images of the hips and femurs, and axial breath-holding MR images of
      the abdomen that allowed measurement of hepatic and splenic volume. The bone
      changes were classified and were correlated with the liver and spleen volumes.
      Specific imaging features of the liver and spleen were noted and correlation
      sought. RESULTS: A statistically significant difference in liver size was found
      between patients with and without avascular necrosis. A statistically significant
      correlation was also found between liver size and avascular necrosis. Patients
      with marrow changes classified as grade 2 or higher were significantly more
      likely to have avascular necrosis. Nineteen percent of patients had splenic
      nodules and 7% had hepatic nodules; however, there was no correlation between the
      nodules and bone changes. CONCLUSION: MR imaging showed a statistical
      relationship between marrow changes, liver size, and avascular necrosis in
      patients with type 1 Gaucher's disease. Knowledge of this relationship may be
      used in dosage and treatment considerations in the follow-up and clinical
      management of these patients.

PMID- 7645478
TI  - Association of sonographically detected subacromial/subdeltoid bursal effusion
      and intraarticular fluid with rotator cuff tear.
AB  - OBJECTIVE: Although an association between sonographically detected joint fluid
      and rotator cuff disease has been reported, the significance of sonographically
      detected subacromial/subdeltoid bursal effusion has not been studied. We examined
      a group of patients who had shoulder sonography and surgery to determine the
      association between bursal and joint effusion and surgically proved tears of the
      rotator cuff. MATERIALS AND METHODS: We retrospectively reviewed the preoperative
      shoulder sonography reports of 163 patients for the presence of fluid within the
      subacromial/subdeltoid bursa or glenohumeral joint. Surgical reports were
      obtained to determine the status of the rotator cuff. The sonographic reports of
      232 asymptomatic shoulders were also reviewed to determine the prevalence of
      fluid within the subacromial/subdeltoid bursa or the glenohumeral joint. RESULTS:
      Sixty-seven (41%) of the 163 patients had a joint effusion, bursal fluid, or
      both. Joint effusion alone was seen in 35 patients. Fourteen of these had a
      normal rotator cuff at surgery, and 21 had a rotator cuff tear (sensitivity, 22%;
      specificity, 79%; positive predictive value, 60%). Bursal fluid alone was seen in
      10 patients, seven of whom had a rotator cuff tear (sensitivity, 7%; specificity,
      96%; positive predictive value, 70%). In 22 patients, fluid was seen in both the
      bursa and the joint; 21 had surgically proved rotator cuff tears (sensitivity,
      22%; specificity, 99%; positive predictive value, 95%). Of the 232 asymptomatic
      shoulders, 16 (6.9%) had isolated joint effusions, eight (3.4%) had isolated
      bursal effusions, and four (1.7%) had both joint and bursal effusions.
      CONCLUSION: The sonographic finding of intraarticular fluid alone (without bursal
      fluid) has both a low sensitivity and a low specificity for the diagnosis of
      rotator cuff tears. However, the finding of fluid in the subacromial/subdeltoid
      bursa, especially when combined with a joint effusion, is highly specific and has
      a high positive predictive value for associated rotator cuff tears.
      Sonographically detected fluid in both the joint and the bursa is an uncommon
      finding in asymptomatic shoulders. The sonographic observation of fluid in the
      subacromial bursa, either isolated or combined with a joint effusion, should
      prompt a careful evaluation of the supraspinatus tendon for tear.

PMID- 7645479
TI  - Acromial angle on radiographs of the shoulder: correlation with the impingement
      syndrome and rotator cuff tears.
AB  - OBJECTIVE: This study was undertaken to determine the reproducibility of
      measurements of an acromial angle on radiographs and to correlate those
      measurements with the presence of the impingement syndrome and rotator cuff
      tears. MATERIALS AND METHODS: Ninety-nine shoulders in 95 patients who had an
      arch radiograph and had undergone shoulder arthroscopy were included in this
      retrospective study. The acromial angle was measured on the arch view of the
      shoulder independently by three observers who were blinded to the name, history,
      and arthroscopic results. The angle was measured at the intersection of lines
      drawn along the inferior cortex of the anterior and posterior portions of the
      acromion. Interobserver variability was determined by the intercorrelation
      coefficient (a test of reproducibility of quantitative measurements). The average
      of the three measurements for each patient was correlated with the preoperative
      diagnosis and the arthroscopic findings. RESULTS: A correlation was found between
      increasing severity of cuff disease as determined on arthroscopy and increasing
      acromial angle (p < .01). In 67 patients (70 shoulders) with impingement,
      patients with a full-thickness tear (29%) accounted for 43% of those with an
      angle of 30 degrees or greater. The average acromial angle for patients with
      impingement was greater than that for either patients with instability or
      patients with trauma (p < .05 for both). An angle of 25 degrees or greater was
      measured in 63% of patients with impingement but in only 18% of those with
      instability. The average acromial angle in patients with impingement and an
      intact rotator cuff was also greater than the average angle in patients with
      instability (p = .001). The interobserver variability had an intercorrelation
      coefficient of 0.90. CONCLUSION: The acromial angle is an objective and fairly
      reproducible measure of anterior acromial shape. The angle is useful in
      identifying patients with a greater likelihood of having a rotator cuff tear and
      in distinguishing patients with primary impingement from those with instability.

PMID- 7645480
TI  - Assessment of articular cartilage thickness of the humeral head: MR-anatomic
      correlation in cadavers.
AB  - OBJECTIVE: The purpose of our study was to evaluate several commonly used MR
      sequences to determine how accurately each demonstrates the thickness of the
      articular cartilage of the humeral head. MATERIALS AND METHODS: Ten cadaveric
      shoulders (age at death, 58-92 years; mean, 79 years) were imaged with fat
      suppressed transaxial T1-weighted spin-echo three-dimensional gradient-recalled
      sequences, both before and after injection of 12 ml of diluted gadopentetate
      dimeglumine. Articular cartilage was measured to the nearest 10th of a millimeter
      on the MR images and corresponding anatomic sections. RESULTS: Cartilage could
      not be differentiated from surrounding structures in 14 of 112 locations (13%) on
      the spin-echo images obtained without contrast material, in 4 of 112 locations
      (4%) on the spin-echo images obtained with contrast material, in 4 of 112
      locations (4%) on the gradient-echo images obtained without contrast material,
      and in 6 of 112 locations (5%) on the gradient-echo images obtained with contrast
      material. Mean true cartilage thickness was 1.23 mm (SD, 0.52 mm). The mean MR
      anatomic differences (absolute values) were 0.38 mm for the spin-echo images
      obtained without contrast material, 0.42 mm for the spin-echo images obtained
      with contrast material, 0.49 mm for the gradient-echo images obtained without
      contrast material, and 0.37 mm for the gradient-echo images obtained with
      contrast material. There was a tendency to overestimate thin cartilage and to
      underestimate thick cartilage. CONCLUSION: Several of the routinely used MR
      sequences, with and without intraarticular contrast medium, may cause errors in
      the assessment of the articular cartilage of the humeral head. Some of these
      errors result from either insufficient contrast between cartilage and surrounding
      structures or inadequately concentrated contrast medium.

PMID- 7645481
TI  - Bucket-handle tears of the medial and lateral menisci of the knee: value of MR
      imaging in detecting displaced fragments.
AB  - OBJECTIVE: A bucket-handle tear of a meniscus is a longitudinal tear with an
      attached fragment displaced away from the meniscus. Several MR findings of bucket
      handle tears have been reported previously. However, the sensitivity of MR for
      detecting the displaced fragment is unknown. We determined the sensitivity of MR
      for detecting a displaced bucket-handle tear and determined how the sensitivity
      varied with tears of different sizes. We also evaluated whether the three
      findings of a displaced fragment differed in frequency between medial and lateral
      tears. MATERIALS AND METHODS: We retrospectively evaluated the MR examinations of
      39 patients with arthroscopically proven bucket-handle tears for signs of a
      displaced meniscal fragment. Thirty-two patients had medial meniscal bucket
      handle tears, and seven had lateral tears. Two observers evaluated each
      examination independently, with discrepancies resolved by consensus of a third
      reader. Each observer evaluated for three findings of a bucket-handle tear: a
      double posterior cruciate ligament sign, a flipped meniscus sign, or a fragment
      in the intercondylar notch. A double posterior cruciate ligament sign is present
      when the meniscal fragment is displaced anterior to the posterior cruciate
      ligament, resembling two ligaments. A flipped meniscus sign occurs when the
      fragment is flipped anteriorly so the anterior horn of the meniscus appears to be
      enlarged. We tested for differences between menisci in the sensitivity for each
      sign using Pearson's chi-squared test or Fisher's exact test. We compared the
      sensitivity of MR for identifying fragments when the tear involved one third, two
      thirds, or the entire meniscus using Spearman's rank correlation. RESULTS:
      Overall sensitivity for a displaced fragment was only 0.64. When the bucket
      handle tear involved the entire meniscus, the displaced fragment could be seen in
      84% of the menisci. The double posterior cruciate ligament sign was seen in 53%
      of the medial and none of the lateral bucket-handle tears (p = .01). The flipped
      meniscus sign was noted in 44% of medial and 29% of lateral menisci (p = .68),
      and a fragment was identified in the intercondylar notch in 66% of medial and 43%
      of lateral menisci (p = .40). CONCLUSION: MR is sensitive for detecting meniscal
      fragments in large bucket-handle tears, but is less so in small tears. The
      flipped meniscus sign and presence of a fragment in the notch were comparably
      useful findings of a displaced fragment in both medial and lateral menisci. The
      double posterior cruciate ligament sign was noted only in medial bucket-handle
      tears.

PMID- 7645482
TI  - Primary cerebral lymphoma.

PMID- 7645483
TI  - Cyclosporine neurotoxicity and its relationship to hypertensive encephalopathy:
      CT and MR findings in 16 cases.
AB  - OBJECTIVE: The neurotoxic effects of cyclosporine therapy are well known but
      poorly understood. Imaging studies typically show subcortical edema predominantly
      affecting the posterior regions of the brain. We sought to determine the causes
      for these findings by comparing radiographic data with various clinical
      parameters. MATERIALS AND METHODS: In a 3-year period, 16 patients with
      neurologic findings attributed to cyclosporine therapy were examined with CT, MR
      imaging, or both. In most cases, imaging was performed both at the onset of the
      neurologic syndrome and after it had resolved. The radiographic findings were
      evaluated with respect to lesion location and changes over time. Various clinical
      and laboratory data obtained throughout the patients' hospital course were also
      reviewed, including cyclosporine levels, blood pressure values, hematologic data,
      and serum levels of cholesterol, magnesium, creatinine, and albumin. RESULTS: The
      only major factor associated with the neurotoxic effects of cyclosporine in all
      patients was systemic hypertension. Microangiopathic hemolytic anemia,
      thrombocytopenia, and hypoalbuminemia were also common, and patients usually
      displayed signs of sympathetic overactivation. The onset of neurologic symptoms
      was unrelated to serum levels of creatinine, magnesium, cholesterol, or
      cyclosporine. The clinical and radiographic findings of these patients were
      identical to those previously reported in patients with hypertensive
      encephalopathy. Findings resolved in all but one patient after reduction of blood
      pressure, with or without reduction in cyclosporine dose. In four patients,
      intracranial hemorrhages occurred during the hypertensive episode, resulting in
      one fatality. CONCLUSION: The clinical and radiologic findings in patients
      showing the neurotoxic effects of cyclosporine appear to be identical to those
      with hypertensive encephalopathy. Other associated factors, such as cyclosporine
      induced vasculopathy or hypoalbuminemia may also play a role in the condition,
      and intracranial hemorrhage may occur owing to associated thrombocytopenia.
      Symptoms generally resolve after reduction of blood pressure, and follow-up is
      usually unnecessary in uncomplicated cases.

PMID- 7645485
TI  - MR imaging of the eyelids: normal and pathologic findings.
AB  - MR imaging is commonly used to evaluate orbital and facial soft-tissue disease.
      Although the eyelids are visible on these images, the radiographic appearance and
      the detailed anatomy of these structures has received little attention in the
      literature [1-4]. Anatomic correlation with MR images may be extremely helpful in
      the accurate interpretation and staging of eyelid malignancies and infections.

PMID- 7645484
TI  - Cerebral metabolites in patients with acute and subacute strokes: concentrations
      determined by quantitative proton MR spectroscopy.
AB  - OBJECTIVE: The purpose of this study was to determine the feasibility of
      measuring concentrations of cerebral metabolites in acute and subacute stroke
      patients using single-voxel localized proton MR spectroscopy and to compare these
      concentrations to those in contralateral brain regions and in normal healthy
      volunteers. SUBJECTS AND METHODS: Single-voxel proton MR spectroscopy and MR
      imaging were performed in 14 stroke patients, at times ranging from 2 hr to 10
      days following the onset of symptoms. Signals from choline, creatine, N-acetyl-L
      aspartate (NAA), and lactate were quantified in the infarcted region (n = 14) and
      in the hemisphere contralateral to the stroke (n = 8) and compared with data
      obtained from a group of 10 control subjects. RESULTS: Infarcts were
      characterized by significantly increased lactate (12 of 14 patients; 7.5 +/- 8.9
      mumol/g wet weight, mean +/- SD) and significantly decreased NAA (12 of 14
      patients; 5.5 +/- 3.2 mumol/g wet weight), compared with contralateral brain
      regions and control data in healthy volunteers. Significant reductions in
      choline, creatine, and NAA were also found in contralateral brain regions
      compared with the control patients. CONCLUSION: Quantitative single-voxel proton
      spectroscopy is feasible for use in clinical studies of acute stroke. Ratio
      measurements or comparison with contralateral metabolites may be misleading
      because all metabolites may change during infarction, and contralateral
      metabolite levels may also be different from normal subjects.

PMID- 7645486
TI  - Three-dimensional projection images of the labyrinth acquired with multislab 3DFT
      fast spin-echo sequence and dual-array surface coil.

PMID- 7645488
TI  - Pulmonary blastomycosis in children: findings on chest radiographs.
AB  - OBJECTIVE: The purpose of this study was to identify characteristic radiographic
      findings in children with pulmonary blastomycosis. SUBJECTS AND METHODS: We
      reviewed the charts and radiographs of 18 children with culture-proven acute
      pulmonary blastomycosis. The 10 boys and eight girls were from 1 to 16 years old.
      Sixteen were Native Canadian Indians, and two were white. All available chest
      radiographs, including those obtained in follow-up after treatment was
      terminated, were reviewed by a pediatric radiologist. Consolidation was
      classified by location and extent, and other abnormalities were noted. RESULTS:
      Initial chest radiographs showed consolidation in 16 patients. Seven patients had
      single lobe involvement, most commonly of the left lower lobe. Nine patients had
      multiple lobe involvement. The left lower lobe was most commonly involved in
      these cases, but the middle lobe was most severely affected. The upper lobes were
      involved only in children with multiple lobe disease and were only mildly
      affected. Cavitation developed in two patients, followed by bronchogenic spread
      of the disease. Pleural effusions were seen in three patients; two also had rib
      lesions. Hilar adenopathy developed in two children. Five patients had
      radiographs available, which had been obtained more than a year after onset, and
      three of these were abnormal. CONCLUSION: The most common radiologic finding in
      children with pulmonary blastomycosis is pulmonary consolidation in one or
      several lobes, which may undergo cavitation. Lymphadenopathy and pleural
      effusions are uncommon. Chronic abnormalities may develop.

PMID- 7645487
TI  - Inflicted skeletal injury: a postmortem radiologic-histopathologic study in 31
      infants.
AB  - OBJECTIVE: The objective of this postmortem study was to use high-detail skeletal
      surveys, specimen radiography, and histopathologic analysis to determine the
      number, distribution, and age of inflicted skeletal injuries in infants studied
      at the University of Massachusetts Medical Center from 1984 to 1994. MATERIALS
      AND METHODS: Thirty-one infants (average age, 3 months) who died with inflicted
      skeletal injuries were studied with high-detail skeletal surveys and specimen
      radiography and histopathologic analysis. The distribution and number of
      fractures was determined for each technique, and dating was performed on the
      basis of radiologic and histologic criteria. The skull fractures noted in 13
      cases were excluded from the numerical analysis. RESULTS: The radiologic
      histopathologic correlation revealed 165 fractures involving the ribs in 84
      (51%), long bones in 72 (44%), bones of the hands and feet in 6 (4%), clavicles
      in 2 (1%), and spine in 1 (< 1%). Of the 72 long bone fractures, the metaphyses
      were involved in 64 (89%, or 39% of the total), and the shaft was involved in 8
      (11%, or 5% of the total). One hundred sixteen fractures were healing, 36 were
      acute, and 13 were of indeterminate age. In all but two infants, at least one
      healing fracture was present. Of fractures diagnosed histopathologically,
      specimen radiography increased the yield of fractures noted on skeletal survey
      from 58% to 92%. CONCLUSION: Most infants who die with inflicted injury have
      fractures at multiple sites. Metaphyseal and rib fractures are much more common
      than long bone shaft injuries, the opposite of the pattern found in older
      children. Because most abused infants who die have evidence of healing fractures
      at the time of autopsy, aggressive radiologic efforts to identify these injuries
      in living as well as in decreased infants appear justified.

PMID- 7645489
TI  - Reduced-size hepatic allograft vascular compression in children: detection with
      color Doppler sonography.

PMID- 7645490
TI  - Stent graft for treatment of an abdominal aortic aneurysm: leak detected by CT.

PMID- 7645491
TI  - Coronary MR angiography after coronary stent placement.

PMID- 7645492
TI  - Vascular imaging with a three-dimensional power Doppler system.

PMID- 7645493
TI  - Gadolinium-based MR contrast media: potential for growth of microbial
      contaminants when single vials are used for multiple patients.
AB  - OBJECTIVE: To assess potential risk if single-dose vials of gadolinium-based
      contrast media are used for multiple patients. The use of multidose vials can
      pose a significant risk if contaminants are accidentally introduced into the
      vials and proliferate. Therefore, we tested the ability of gadolinium-based
      contrast to support the growth of a variety of microbial pathogens. MATERIALS AND
      METHODS: We collected the unused portions of 15 single-use vials of gadolinium
      based contrast media. The residual contrast material was refrigerated after use
      and checked for sterility prior to inoculation with a selection of gram-positive
      and gram-negative bacteria and yeast. Contrast material was incubated at room
      temperature and at 4 degrees C, and quantitative cultures were performed at 0,
      24, 48, and 72 hr and at 7 days. RESULTS: No microbial growth occurred from
      cultures of the used contrast solutions prior to inoculation. None of the
      organisms tested in our study proliferated in the contrast material. All test
      organisms persisted at least 48 hr after inoculation at both temperatures. At 7
      days, Staphylococcus aureus, Streptococcus epidermidis, and Corynebacterium
      jeikeium were recovered in significant quantities. Colony counts of Serratia
      odorifera rapidly decreased at room temperature but persisted beyond 7 days at 4
      degrees C. CONCLUSION: The risk of contaminating vials of contrast agents
      punctured aseptically is small. Our study demonstrates a lack of proliferation of
      organisms in the two gadolinium-based compounds tested, suggesting that these
      solutions could be used for more than one procedure.

PMID- 7645494
TI  - Applications of the Amplatz snare device during interventional radiologic
      procedures.
AB  - The Amplatz gooseneck snare (Microvena, St. Paul, MN) is a recently developed
      device for the percutaneous removal of intravascular foreign bodies [1-5] (Fig.
      1). In the past several years, various other applications of this snare system
      have been devised for placing, replacing, repositioning, or removing guidewires,
      catheters, and other devices during interventional procedures. The Amplatz
      gooseneck snare, which has been described [1], comes in a variety of loop sizes
      and is provided with either 4- or 6-French guiding catheters, although
      substitution with any of several soft, blunt-tipped guiding catheters is possible
      [5]. The principal advantage of the Amplatz snare over past systems is that the
      loop is at a right angle to the catheter, easing the capture of foreign bodies,
      devices, or catheters.

PMID- 7645496
TI  - The role of the manuscript reviewer in the peer review process.
AB  - Peer review of submitted manuscripts is recognized as a critical component of the
      publication process in all major medical journals. It lends respectability and
      scientific credibility to those journals that have adopted the process [1]. This
      function is delegated to a group of persons who perform the task selflessly and
      without compensation. Of the many facets of the peer review process, the
      selection of manuscript reviewers and their subsequent interaction with both
      editors and authors may be so poorly understood by aspiring authors that certain
      misconceptions ensue. Authors of rejected manuscripts may fear that reviewers
      have acted in an arbitrary and possibly censorial fashion [2, 3]. Conversely,
      authors of accepted manuscripts who face a mountain of revisions may wonder if
      such an effort is likely to improve their manuscript [4, 5]. The following
      questions come to mind: Where do the reviewers come from? What do they do, and
      what constitutes a good reviewer? What power do they have? How is reviewer
      performance measured? Can the editor recognize publicly the good reviewer? Are
      reviewers really blinded? How does one become a good reviewer? Who will be the
      reviewers of the future? While looking at these questions, we should consider
      objective approaches of assessing reviewer quality and wonder whether they would
      improve the quality of the published manuscript.

PMID- 7645495
TI  - Imaging systems evaluation: effect of subtle cases on the design and analysis of
      receiver operating characteristic studies.
AB  - OBJECTIVE: Large-scale receiver operating characteristic (ROC) studies are
      expensive and time-consuming. If most of the difference in diagnostic accuracy
      occurs in a subset of subtle cases, considerable effort could be saved by
      restricting comparisons to this subset. We investigate the effect of subtle cases
      on diagnostic accuracy, the magnitude of error that can occur because of an
      imbalance of subtle cases in two groups, and the potential for sample size
      reductions if only subtle cases are used. METHODS: Data from a previous study of
      posteroanterior chest radiographs were reanalyzed separately for subsets of
      typical cases and subsets of subtle cases. Actually positive and actually
      negative cases were classified as subtle or typical and as difficult or easy for
      diagnosis of the specific abnormality. The area under the ROC curve (Az) was used
      as the measure of diagnostic accuracy. Pairwise comparisons were done among three
      techniques and for the detection of nodules and interstitial disease. RESULTS:
      The performance index (Az) was significantly (> or = 25%) lower for the subset of
      subtle cases as compared with the subset of typical cases. The difference in
      observer performance between two techniques was more often greater in the subset
      of subtle cases than in the subset of typical cases. CONCLUSION: The difference
      in diagnostic accuracy between the subset of typical cases and the subset of
      subtle cases is large enough that a difference in the proportion of subtle cases
      in two samples could result in clinically significant false differences in
      observer performance. Furthermore, the generally larger difference observed in
      the group of subtle cases suggests that sample sizes for some experiments could
      be reduced by 45-90% if the experiment were restricted to subtle cases.

PMID- 7645497
TI  - American martyrs to radiology. Lawrie Byron Morrison (1875-1933). 1936.

PMID- 7645498
TI  - American martyrs to radiology. Morrison and early radiologic technology.

PMID- 7645499
TI  - A history of the Department of Radiology at Duke University Medical Center.

PMID- 7645500
TI  - 95th annual meeting of the ARRS: gold medal winners.

PMID- 7645502
TI  - What is the optimal pitch on helical CT for evaluation of aortic or pulmonary
      embolic disease?

PMID- 7645503
TI  - In patients with left lower quadrant pain, should barium enema or CT be used for
      initial evaluation?

PMID- 7645501
TI  - High costs of low-osmolality contrast media.

PMID- 7645504
TI  - Given the improvement in pelvic coils for MR, is an endorectal coil necessary to
      evaluate prostate carcinoma?

PMID- 7645505
TI  - MR imaging studies on patients with painful shoulders.

PMID- 7645506
TI  - Fast spin echo techniques are being widely used. What is the role of fast spin
      echo sequences compared with spin echo sequences in shoulder and knee MR imaging
      examinations?

PMID- 7645507
TI  - Closing the circle.

PMID- 7645508
TI  - Hemomediastinum and bilateral hemothorax: idiopathic spontaneous presentation.

PMID- 7645509
TI  - Traumatic gallbladder rupture: CT diagnosis.

PMID- 7645510
TI  - Re: Role of imaging in the evaluation of small-bowel obstruction.

PMID- 7645512
TI  - Re: Postoperative changes, complications, and recurrent disease after Whipple's
      operation.

PMID- 7645511
TI  - Obstructing postinflammatory polyps of the colon: CT and sonographic findings.

PMID- 7645513
TI  - Three-dimensional power Doppler detection of prostatic cancer.

PMID- 7645514
TI  - Plasmacytoma of the sacrum: fluid-fluid levels on MR images.

PMID- 7645515
TI  - Progression from simple joint effusion to extensive pigmented villonodular
      synovitis of the hip within 2 years: demonstration with MR imaging.

PMID- 7645516
TI  - Focal regeneration of irradiated bone marrow: a pitfall in MR imaging.

PMID- 7645517
TI  - Wegener's granulomatosis in children.

PMID- 7645518
TI  - Should private practice radiologists measure the hippocampus in seizure patients
      with suspected temporal lobe epilepsy?

PMID- 7645519
TI  - Shotgun pellet embolus to the basilar artery.

PMID- 7645520
TI  - Re: Timely diagnosis of brain death in an emergency trauma center.

PMID- 7645521
TI  - A symposium: from mitochondrial metabolism to coronary artery disease: new trends
      in the management of myocardial ischemia. Introduction.

PMID- 7645522
TI  - Combination therapy of trimetazidine with diltiazem in patients with coronary
      artery disease. Group of South of France Investigators.
AB  - The efficacy of trimetazidine, an antianginal agent with a direct effect on
      ischemic myocardium, has been tested alone or in combination with beta blockers
      or nifedipine. The combination with diltiazem, a widely used calcium antagonist,
      has not been studied. The aim of this study was to evaluate the potential benefit
      of oral trimetazidine (20 mg 3 times daily) in combination with oral diltiazem
      (60 mg three times daily). This was a multicenter, placebo-controlled study with
      a follow-up period of 6 months. Patients with stable angina and a positive
      exercise electrocardiogram before and after 15 days of diltiazem therapy were
      included. The 67 patients were randomized to diltiazem plus placebo (group I, 35
      patients) and diltiazem plus trimetazidine (group II, 32 patients). Follow-up
      included a bicycle ergometer maximal exercise test and a physical examination at
      inclusion and at 3 and 6 months. The 2 groups were similar in terms of ergometric
      parameters, except for the ischemic threshold, defined as the time to 1-mm ST
      segment depression. The latter was shorter in group II. Comparison of exercise
      tests performed at inclusion and after 6 months of therapy in both groups showed
      that the ischemic threshold was significantly prolonged (2 minutes 41 seconds; p
      < 0.001) in group II. This was not the case for group I, which showed a 41-second
      prolongation only (difference not significant). The work (kPM) produced at 1-mm
      ST-segment depression was also significantly increased in group II (1,445.9 kPM;
      p < 0.001) compared with group I (563.7 kPM; p = 0.012).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7645523
TI  - Metabolic disturbances during myocardial ischemia and reperfusion.
AB  - Myocardial ischemia is defined as an imbalance between fractional uptake of
      oxygen and the rate of cellular oxidation in the heart. This condition may have
      several potential outcomes: (1) when ischemia is brief, a transient post-ischemic
      ventricular dysfunction occurs on reperfusion, a condition termed "stunned
      myocardium"; (2) when it is prolonged and severe, irreversible damage occurs,
      with no recovery in contractile function upon reperfusion; (3) when ischemia is
      less severe, but still prolonged, the myocytes may remain viable but exhibit
      depressed contractile function. Under this condition, named "hibernating
      myocardium," the reperfusion is able to restore contractility. During these
      different ischemic conditions many biochemical changes happen; initially they
      represent a defensive and protective reaction against ischemic insults such as
      cellular acidosis and increase of inorganic phosphate levels that rapidly abolish
      the contractile activity. But with the prolongation of ischemia or restoration of
      the coronary flow, alterations in ions and overall Ca2+ homeostasis occur,
      together with an oxidative stress mediated by oxygen free radicals, which are not
      adequately counteracted by the cellular antioxidant defenses. All these
      biochemical alterations lead to membrane damage, mitochondrial swelling, and
      irreversible deterioration of contractile function.

PMID- 7645524
TI  - Trimetazidine effects on the damage to mitochondrial functions caused by ischemia
      and reperfusion.
AB  - Trimetazidine (TMZ) is an anti-ischemic compound whose precise mode of action is
      unknown, although several studies have suggested a metabolic effect, and there
      have been reports of protection of mitochondria against oxidative stress damage.
      Using a Langendorff rat heart model, we examined the effects of TMZ on the
      mitochondrial damage following 30 minutes of ischemia and 5 minutes of
      reperfusion. Mitochondrial respiration with succinate, glutamate-malate and
      ascorbate-N,N,N',N'-tetramethylphenylenediamine (TMPD) as substrates was
      significantly decreased following ischemia-reperfusion. Preperfusion with 10(-5)
      M TMZ had no effect on these rates in normoxic or ischemic hearts. However, 10(
      3) M TMZ significantly decreased the glutamate-malate rate in mitochondria from
      normoxic hearts, and this rate was not further decreased following ischemia
      reperfusion, and 10(-3) M TMZ also partially protected ascorbate-TMPD activity.
      The effect on glutamate-malate was probably due to an inhibition of complex I by
      TMZ, which specifically inhibited reduced nicotinamide-adenine-dinucleotide
      cytochrome c reductase and complex I in lysed mitochondria. We also studied the
      effects of TMZ on the activity of pyruvate dehydrogenase (PDH) in normoxic and
      ischemic hearts perfused with 0.5 mM palmitate, which caused the enzyme to be
      almost completely inactivated. After short periods of ischemia (10-20 minutes)
      the PDH inactivation by palmitate was progressively lost. Preperfusion with 10(
      5) M TMZ had a tendency to decrease lactate dehydrogenase release, accompanied by
      a maintenance of the inhibition of PDH by palmitate. This may allow the heart to
      oxidize fatty acids preferentially during reperfusion, hence removing possible
      toxic acyl esters.

PMID- 7645525
TI  - Trimetazidine: in vitro influence on heart mitochondrial function.
AB  - The mechanism of action of the antianginal trimetazidine (TMZ) remains largely
      unknown. In cultured rat ventricular myocytes in physiologic conditions, TMZ (5 x
      10(-4) M) reduced the plateau potential level, the upstroke velocity, and the
      spontaneous action potential rate. When the cardiomyocytes were submitted to
      hypoxia (150 or 240 minutes) in a glucose-free medium, treatment with TMZ largely
      prevented the hypoxia-induced electromechanical alterations, i.e., the decrease
      in plateau amplitude, in resting membrane potential, in action potential
      duration, in rate, and in contractility. No hypoxia-induced arrhythmia was
      observed in the TMZ-treated cells. Moreover, the lactate dehydrogenase leakage
      was significantly reduced in the TMZ-treated cardiomyocytes (-58% and -36%, after
      150 and 240 minutes of hypoxia, respectively). The drug was not efficient in
      reducing the hypoxia-induced decrease in adenosine triphosphate (ATP) content.
      The cellular ATP content was slightly lower in the TMZ-treated cells in normoxic
      conditions and in hypoxic conditions, but only in the glucose-free medium. To
      investigate further the relation between TMZ and energy metabolism, the
      respiration parameters were measured in heart mitochondria isolated from control
      and TMZ-treated rats (6 mg/kg/day, 7 days) with different substrates. This
      treatment resulted in a slight alteration of pyruvate oxidation, which was
      observed in the absence and in the presence of TMZ (10(-4) M) in the respiration
      medium. Conversely, a potent inhibition of palmitoylcarnitine oxidation was
      measured when TMZ was added to the respiration medium. Neither pretreatment of
      the rats, nor addition of TMZ to the medium affected the oxidation of glutamate
      or citrate.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7645526
TI  - Trimetazidine and myocardial ischemic contracture in isolated rat heart.
AB  - Trimetazidine, a drug thought to improve ischemia by a metabolic mechanism, was
      able to inhibit the formation of ischemic contracture in isolated hearts taken
      from rats pretreated with the drug. The mechanism of this potentially important
      action is unknown.

PMID- 7645527
TI  - From antianginal drugs to myocardial cytoprotective agents.
AB  - The existing major classes of antianginal drugs improve quality of life in
      patients with coronary artery disease, but mortality in these patients remains
      unacceptably high. In order to limit the complications of the disease, it is
      vital to limit myocyte loss. Potentially, this can be achieved not only by
      prophylaxis, but also by protection, against ischemia. Any therapy that increases
      myocardial resistance to ischemia will protect against cell death and prolong the
      life of the myocyte, and possibly the patient. The mechanisms of cell damage
      during ischemia, and possible therapeutic interventions, are discussed.

PMID- 7645528
TI  - Limitation of infarct size by trimetazidine in the rabbit.
AB  - The influence of trimetazidine on infarct size was studied with a 45-minute
      period of coronary occlusion followed by 24 hours of blood reperfusion in the
      rabbit heart. The groups studied were 7 control rabbits and 7 rabbits pretreated
      with 3 mg/kg of trimetazidine. Twenty-four hours after coronary artery ligation
      for 45 minutes, infarct size was measured in myocardial slices using
      trinitrophenyl tetrazolium staining, and the area at risk was determined by
      injection of zinc/cadmium particles and delineated at the same time by imaging,
      under fluorescent light, the areas of tissue that fluoresced. The range of area
      at risk was similar in both of the groups. There was a significant reduction in
      the size of infarct that developed in the trimetazidine-treated group when
      compared with the control rabbits. It is concluded that pretreatment with
      trimetazidine in the blood-perfused rabbit heart is effective in reducing
      myocardial infarct size.

PMID- 7645529
TI  - Improvement of long-term preservation of the isolated arrested rat heart by
      trimetazidine: effects on the energy state and mitochondrial function.
AB  - Rat hearts, arrested in situ after intracaval injection of a cardioplegic
      solution, were preserved for 15 hours at 4 degrees C either by simple immersion
      or by low-flow (0.3 mL/min) perfusion. After preservation under both conditions,
      the left ventricular pressure developed by the reperfused hearts reached 8% and
      43% of the control value (80 mm Hg), respectively. The addition of trimetazidine
      (TMZ; 10(-6) M) to the cardioplegic solution induced an improvement in functional
      recovery (by 2.4 and 1.5, respectively). This effect of TMZ was accompanied by a
      better energy profile illustrated by a 2-fold increase in the adenosine
      triphosphate to inorganic phosphate ratio and a reduction of intracellular
      acidosis as determined by 31P nuclear magnetic resonance spectroscopy. The
      function of the mitochondria (state 3, reduced nicotinamide-adenine dinucleotide
      [NADH] formation) isolated from the preserved hearts was significantly depressed
      in the stored hearts. The addition of TMZ to the cardioplegic solution partially
      protected oxoglutarate (and succinate) mitochondrial respiration and induced an
      increase in Ca2+ triggered NADH formation. These results show that the bioenergy
      status of the myocardial cell in isolated arrested stored rat heart is improved
      by the presence of TMZ in the preservation solution. Moreover, the experiments
      demonstrate that this effect includes protection of mitochondrial function and
      suggest that the drug could exert some control in the Ca2+ regulation of
      mitochondria.

PMID- 7645530
TI  - Trimetazidine European Multicenter Study versus propranolol in stable angina
      pectoris: contribution of Holter electrocardiographic ambulatory monitoring.
AB  - The major objective of the Trimetazidine European Multicenter Study (TEMS) was to
      compare in a double-blind trial the anti-ischemic effects of trimetazidine (20 mg
      3 times daily) with those of propranolol (40 mg 3 times daily). The inclusion
      criteria were based on an abnormal response to a multistage exercise test. After
      3 months of treatment the improvements noted in all exercise testing data were
      similar in the trimetazidine and propranolol groups; similar data were obtained
      for the grades and severity of anginal attacks during daily life (from patient
      diaries). A 24-hour Holter monitoring was performed at entry and at the end of
      the study, but an abnormal Holter monitoring (1-mm ST-segment depression during
      at least 1 minute) was not an inclusion criterion. This explains why at entry
      only 50% of the patients in both groups had an abnormal Holter recording. After 3
      months of treatment, there were no significant differences between the 2 groups,
      but we observed a trend toward a decrease in ambulatory ischemia in the
      trimetazidine group and a trend toward an increase in ambulatory ischemia in the
      propranolol group. These data in the propranolol group are in total disagreement
      with the available literature on beta blockers, which was due to a totally
      erratic behavior pattern in 2 patients in the propranolol group. When we excluded
      these 2 erratic cases from the propranolol group and extended our analysis to all
      available paired comparisons (day -14 to day 30 and day 0 to day 90), we were
      able to compare 44 and 60 observations, both off therapy and on either
      propranolol or trimetazidine, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7645531
TI  - Treatment of amyloidosis.
AB  - Amyloidosis is the extracellular deposition of normally soluble autologous
      protein in a characteristic abnormal fibrillar form. Systemic amyloidosis and
      some local forms are progressive, cause major morbidity, and are often fatal. No
      treatment specifically causes the resolution of amyloid deposits, but therapy
      that reduces the supply of amyloid fibril precursor proteins can improve survival
      and preserve organ function. Major regression of amyloid occurs in at least a
      proportion of such cases, suggesting that the clinical improvement reflects
      mobilization of amyloid. The clearest evidence for regression of amyloid has been
      obtained in juvenile rheumatoid arthritis patients with AA amyloidosis treated
      with chlorambucil. This drug suppresses the acute phase production of serum
      amyloid A protein, the precursor of AA amyloid fibrils, and is associated with
      remission of proteinuria and greatly improved survival. In many such patients,
      scintigraphy with serum amyloid P component shows major regression of amyloid
      over 12 to 36 months and frequently reveals a discrepancy between the local
      amyloid load and organ dysfunction. Measurement of target organ function is
      therefore not an adequate method for monitoring treatment aimed at promoting the
      resolution of amyloid. In monoclonal immunoglobulin light chain (AL) amyloidosis
      the aim of treatment is to suppress the underlying B-cell clone and, therefore,
      production of the amyloid fibril precursor protein. This can be difficult to
      achieve or sustain and, since the prognosis is so poor, many patients die before
      benefits of therapy are realized. A recent development has been the introduction
      of liver transplantation as treatment for familial amyloid polyneuropathy caused
      by transthyretin gene mutations. This leads to the disappearance of variant
      transthyretin from the plasma and halts progression of the neurologic disease.
      Features of autonomic neuropathy frequently ameliorate, and improvement in
      peripheral motor nerve function has been recently reported. Serum amyloid P
      component scans show regression of associated visceral amyloidosis. This surgical
      form of gene therapy holds much promise for patients with familial amyloid
      polyneuropathy and has been widely adopted. The only other form of amyloidosis in
      which the supply of the fibril precursor protein can be sharply reduced is beta
      2M amyloidosis in long-term hemodialysis patients. Renal transplantation lowers
      the plasma concentration of beta 2M to normal levels and is associated with rapid
      improvement of the osteoarticular symptoms. Preliminary observations suggest that
      the beta 2M amyloid deposits also can regress in some patients.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7645532
TI  - Apoptosis in human immunodeficiency virus-associated nephropathy.
AB  - Focal segmental glomerulosclerosis associated with human immunodeficiency virus
      nephropathy (HIVFGS) involves glomeruli, tubules, and interstitium. Its
      pathogenesis is unknown, but HIV peptides may be critical in its development.
      Human immunodeficiency virus peptides and peptide-antibody complexes are
      immunomodulatory, and are associated with apoptosis in lymphoid cells. To
      determine whether apoptosis is present in HIVFGS, renal biopsy specimens of eight
      patients with HIVFGS were compared with those of 10 patients with idiopathic
      focal glomerulosclerosis (FGS) using the Apoptag kit (Oncor, Gaithersburg, MD),
      which detects single cell apoptosis in formalin-fixed tissue by staining 3'
      nucleosome fragments with digoxigenin-labeled nucleotides after terminal
      deoxynucleotidyl transferase enzyme treatment. Apoptosis was scored per
      glomerulus, in total renal tissue sectioned, and in tubules and interstitium per
      square millimeter using a computerized digital image analyzer. There was no
      difference between the number of apoptotic cells per glomerulus or per square
      millimeter of interstitium in patients with FGS and HIVFGS. There were greater
      numbers of tubular apoptotic cells per square millimeter (2.1 +/- 0.9 v 0.15 +/-
      0.08; P = 0.03) in HIVFGS compared with idiopathic FGS. The difference between
      apoptotic cells per total square millimeter of renal tissue (2.8 +/- 1.2 v 0.7 +/
      0.3) approached significance (P = 0.066). Apoptosis may be associated with the
      pathogenesis of HIV nephropathy and may be an important determinant of the
      tubular disease in HIVFGS.

PMID- 7645533
TI  - Diagnosis of iron deficiency anemia in renal failure patients during the post
      erythropoietin era.
AB  - The purpose of this study was to evaluate the sensitivity and specificity of
      laboratory methods in the diagnosis of posterythropoietin-era, iron-deficient,
      chronic renal failure patients. The patient population comprised 25 anemic
      (hemoglobin < 11 g/dL) patients with creatinine greater than 3 mg/dL; 20 were
      dialysis patients, two were transplant patients, and three patients had renal
      failure from other causes. Criteria for study inclusion were as follows: bone
      marrow iron was the reference standard and was graded 0 to +4, ranging from
      absent to diffuse homogeneous iron staining; serum ferritin concentration and
      serum transferrin saturation were tested in terms of sensitivity and specificity.
      The reference standard indicated that iron deficiency existed in 40% of patients.
      Neither serum ferritin nor transferrin saturation were completely adequate
      diagnostic tools. Serum ferritin levels less than 200 ng/dL were 100% specific
      for the diagnosis but only 41% sensitive. Transferrin saturation of less than 20%
      was 88% sensitive, but only 63% specific. By excluding patients with
      hypoproteinemia (transferrin values of < 150 mg/dL), the sensitivity of the test
      increased to 100% and the specificity to 80%. We conclude that transferrin
      saturation is an adequate screening tool in anemic chronic renal failure
      patients, provided that hypoproteinemia is not present. By determining both the
      serum ferritin concentration and the transferrin saturation, a high sensitivity
      and specificity can be achieved, even in patients with hypoproteinemia.
      Furthermore, we believe that on this basis, iron therapy in patients with renal
      insufficiency can be improved.

PMID- 7645534
TI  - Lupus nephritis in Thailand: clinicopathologic findings and outcome in 569
      patients.
AB  - The prognosis of lupus nephritis patients in Thailand has been reported to be
      poorer than that in Western countries since 1978. After a great evolution in
      management, we re-evaluate the long-term outcome in patients who were treated and
      followed up at Siriraj Hospital in Bangkok from 1984 to 1991. Clinical and
      pathologic records were collected from 569 patients (515 females and 54 men) who
      were followed up for a mean period of 38.7 +/- 34.6 months. The mean age was 28
      +/- 10 years and the median duration of symptoms prior to admission was 7 months.
      Hypertension was diagnosed in 32.4% of patients and 41.3% had serum creatinine
      greater than 1.5 mg/dL. Nephrotic-range proteinuria was found in 43.6% of
      patients and creatinine clearance less than 50 mL/min was found in 58.0%. Of the
      314 patients who underwent renal biopsy, the most common histologic finding was
      diffuse proliferative glomerulonephritis (61.5%). The overall probability of
      survival was 76.5% at 60 and 90 months after diagnosis. Initial presence of
      hypertension, renal insufficiency (creatinine clearance < 25 mL/min), and World
      Health Organization histology class IV and III in the biopsied patients were the
      three independent factors significantly associated with lower survival
      probability. Neither gender nor amount of proteinuria was the predictive factor
      for poor outcome. During the follow-up period, 89 patients died and two patients
      entered a chronic dialysis program. The two leading causes of death were
      infection (50.5%) and uremia (28.6%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7645535
TI  - Trends in renal disease morbidity and mortality in the United States, 1979 to
      1990.
AB  - Four indices of morbidity and mortality due to seven groups of renal diseases are
      evaluated in the United States for the period 1979 through 1990. These indices
      include mortality, hospitalization, doctor's office visits, and prevalence. Age
      adjusted and age-specific rates are calculated. Estimates are provided for racial
      , ethnic-, and gender-specific subpopulations. The burden of some diseases had
      decreased, especially renal infections. Most indices of the burden of diabetes
      with renal involvement and hypertensive renal disease have increased, especially
      among segments of the population that are growing. For many groups of disorders
      examined, men have experienced an increasing burden of disease over the 12 years
      evaluated. These data support current trends in renal failure and serve to
      generate hypotheses regarding renal disease patterns. The magnitude of the burden
      of renal disease and the trends toward increasing rates indicate that renal
      disease is a large and growing clinical and public health problem. Major
      improvements are needed in the range and accuracy of diagnosis and of reporting
      renal-related conditions, and additional resources need to be brought to the
      problem of renal-related morbidity. This is a US government work. There are no
      restrictions on its use.

PMID- 7645536
TI  - Acute decreases in serum potassium augment blood pressure.
AB  - Potassium depletion is a risk factor for cardiovascular diseases, including
      hypertension, and frequently is encountered in patients with end-stage renal
      disease. Since the treatment of end-stage renal disease might result in K+
      depletion and postdialysis hypokalemia, we investigated the relationship between
      acute K+ removal by hemodialysis and changes in blood pressure at the completion
      of treatment compared with predialysis and 1-hour postdialysis blood pressure.
      The effects of three different dialysate potassium concentrations ([K+]d; 1.0,
      2.0, and 3.0 mmol/L) were investigated in 11 patients. Hemodialysis-induced K+
      removal, serum [K+], total body K+, and blood pressure were measured. The use of
      1.0, 2.0, or 3.0 mmol/L [K+]d resulted in the removal of 77.0 +/- 6.5, 54.5 +/-
      7.9, and 42.5 +/- 9.9 mmol of K+ per treatment, respectively (P < 0.05, [K+]d 1.0
      v [K+]d 3.0). Predialysis and postdialysis serum [K+] were 4.9 +/- 0.2 and 3.6 +/
      0.1 mEq/L for 1.0 mmol/L [K+]d, 5.1 +/- 0.3 and 3.9 +/- 0.1 mEq/L for 2.0 mmol/L
      [K+]d, and 5.3 +/- 0.3 and 4.2 +/- 0.2 mEq/L for 3.0 mmol/L [K+]d, respectively
      (P < 0.001 for each [K+]d). The baseline total body K+ corrected for gender, age,
      and race was 92% of predicted normal level and did not change significantly with
      the use of different [K+]d. Blood pressure decreased during hemodialysis as
      excess fluid was removed, regardless of [K+]d. Significant increases in blood
      pressure did occur 1 hour postdialysis compared with levels measured at the
      completion of treatment ("rebound hypertension") when hemodialysis was performed
      with 1.0 and 2.0 mmol/L, but not with 3.0 mmol/L [K+]d.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7645537
TI  - Removal of iron dextran by hemodialysis: an in vitro study.
AB  - Intravenous iron dextran is frequently prescribed for iron-deficient hemodialysis
      patients, a practice that has increased during the erythropoietin era. Whether
      iron dextran is removed by hemodialysis has been a concern, especially for high
      permeability membranes. The purpose of this in vitro study was to measure iron
      dextran clearance by nine different hemodialyzers (Fresenius F3, F8, and F80B;
      Baxter CF25, CA150, CA210, and CT190; Toray BK2.1P; and Hospal Filtral 16)
      representing six types of membranes (polysulfone, cuprophane, cellulose acetate,
      cellulose triacetate, polymethylmethacrylate, and polyacrylonitrile) and
      including membranes considered high efficiency and high flux. Clearances were
      assessed using a closed-loop, fixed-volume reservoir model. Absolute drug removal
      also was determined over the 30-minute experiments. Iron dextran clearance did
      not exceed 25 mL/min, and clearances also were minimal after a single automated
      reuse with glutaraldehyde sterilant. A maximum of 8% of iron dextran was removed
      during the experiment. We conclude that iron dextran clearance by the nine
      hemodialyzers studied was small or too low to be detected in this sensitive in
      vitro dialysis system and that adjusting dosing schedules is not needed.

PMID- 7645538
TI  - Intravenous versus subcutaneous dosing of epoetin alfa in hemodialysis patients.
AB  - Hemodialysis patients were studied to determine whether the dose of recombinant
      human erythropoietin (Epoetin alfa; Amgen Inc, Thousand Oaks, CA) required to
      maintain a therapeutic hematocrit level changed when the route of administration
      was switched from intravenously (IV) three times per week to subcutaneously (SC)
      three times per week. Thirteen to 16 weeks after patients were changed from IV
      three times per week to SC three times per week treatment, the Epoetin alfa
      requirement was reduced by 18.5% +/- 3.8% (P < 0.001; n = 72), and after 21 to 24
      weeks of SC treatment the mean dosage had decreased from the IV dose by 26.5% +/-
      4.2% (P < 0.001; n = 41). Sixty-one percent (44 of 72) of patients experienced
      maintenance-dose reductions over 13 to 16 weeks of treatment and 80% (33 of 41)
      were maintained on lower weekly doses after 21 to 24 weeks of treatment than at
      baseline (IV). There was interpatient variability, however: 26% of the patients
      required greater doses SC than IV following 13 to 16 weeks of SC treatment, and
      15% required greater doses SC than IV following 21 to 24 weeks. On completing the
      initial SC three-times-per-week stage of the study, patients were randomized to
      one of three SC dosing strategies for an additional 12 weeks: (1) once per week,
      (2) three times per week Epoetin alfa diluted 1:2 with bacteriostatic saline to
      mitigate stinging at the injection site, or (3) continued three times per week
      with undiluted Epoetin alfa. Patients who were switched to administration of SC
      once per week undiluted Epoetin alfa (n = 20) had their total weekly dose lowered
      by 18.0% +/- 9.4% (P > 0.05), but the mean hematocrit for this cohort also
      decreased, from 34.3% +/- 3.0% to 32.4% +/- 3.9% (P > 0.05), rendering dose
      comparison between the two schedules ambiguous. The maintenance dose for patients
      who received Epoetin alfa diluted 1:2 with bacteriostatic saline (n = 23) did not
      differ from the undiluted three times per week dose at the end of stage 1. The
      third cohort of patients (n = 24), who continued to receive undiluted Epoetin
      alfa on the same SC three-times-per-week schedule, did not require a significant
      change in dosage over the ensuing 12 weeks. Comparison of SC three times per week
      mean dosage after an average of 32 weeks following the switch from IV three times
      per week for this latter cohort revealed a decrease of 23.5% +/- 6.5% (P <
      0.001).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7645539
TI  - Vascular access thrombosis in new hemodialysis patients.
AB  - This study identifies factors that are associated with the risk of access
      thrombosis in 267 new hemodialysis patients. There are few longitudinal studies
      evaluating the risk of access thrombosis despite the need for long-term use of
      the access for maintenance hemodialysis. We used a prospective design following
      patients from 26 providers in Renal Network Council #12 (Iowa, Missouri, Kansas,
      and Nebraska) for 1 year who were starting hemodialysis. There were significant
      increases in access thrombosis relative risk (RR) associated with the placement
      of a polytetrafluoroethylene graft compared with patients with the arteriovenous
      fistula (RR 1.98; 95% confidence interval [CI] = 1.3, 3,01). The probability of
      remaining thrombosis free 90 days after first use was 90.1% (95% CI = 82.9, 94.4)
      for arteriovenous fistula patients, but only 71.6% (95% CI = 63.5, 78.2) for
      polytetrafluoroethylene graft patients. In arteriovenous fistula patients with
      more than 30 days maturity time the risk of thrombosis was significantly lower
      than in those with less maturity time (RR 0.40; 95% CI = 0.14, 0.84); however,
      there was no significant difference for maturity time among patients with a
      polytetrafluoroethylene graft. Reduced thrombosis risk also was observed in
      patients with dialyzer blood flow rates greater than 300 mL/min (RR 0.66; 95% CI
      = 0.44, 0.99). Total heparin dose and erythropoietin therapy were not associated
      with the risk of thrombosis. No differences in risk were found for age, renal
      diagnosis, or type of dialyzer.

PMID- 7645540
TI  - Anticardiolipin antibody in patients on maintenance hemodialysis and its
      association with recurrent arteriovenous graft thrombosis.
AB  - To investigate the relationship between dialysis access thrombosis (arteriovenous
      grafts [AVG] and arteriovenous fistulas [AVF]) and the presence of elevated
      concentration of immunoglobulin G-anticardiolipin antibody (IgG-ACA), we
      conducted a cross-sectional study of all patients, in a single dialysis facility,
      who had a minimum of 6 months of uninterrupted hemodialysis. Episodes of
      thrombosis of AVGs and AVFs in the preceding 30 months were documented and each
      patient's IgG-ACA titer was determined. Sixteen of 74 patients with AVGs (22%)
      had a raised titer of IgG-ACA compared with only one of 17 patients (6%) with
      AVFs. In the patients with AVGs the odds ratio for patients with raised IgG-ACA
      titer to have experienced two or more episodes of thrombosis, compared with none
      or only one episode, was 3.7 (95% confidence interval, 1.2 to 11.8; P < 0.04). No
      events of AVF thrombosis were encountered during the same period. We conclude
      that in end-stage renal disease patients undergoing hemodialysis, there is a
      greater prevalence of elevated IgG-ACA titer in patients with AVGs than in
      patients with AVFs, and this in turn is associated with increased odds of having
      had recurrent AVG thrombosis.

PMID- 7645541
TI  - Comorbidity, urea kinetics, and appetite in continuous ambulatory peritoneal
      dialysis patients: their interrelationship and prediction of survival.
AB  - Comorbidity, urea kinetics (Kt/V and normalized protein catabolic rate), dietary
      protein, total calorie intake, and plasma albumin were measured in 97 continuous
      ambulatory peritoneal dialysis patients followed prospectively for 30 months.
      Comorbid disease was graded severe in 12 patients, intermediate in 29, and absent
      in 56. At entry to the study comorbidity was associated with increased age (P =
      0.001), lower dietary protein (P = 0.015) and calorie intake (P = 0.02), and a
      lower plasma creatinine (P = 0.026). Trends toward lower Kt/V and albumin were
      not significant, and normalized protein catabolic rate was unaffected. Ability of
      these measures to predict mortality was assessed by univariate and multivariate
      analysis using Cox's proportional hazard model. On univariate analysis,
      comorbidity (P < 0.0001), age (P = 0.0001), Kt/V (P = 0.009), plasma albumin (P =
      0.009), calorie intake (P = 0.035), and dietary protein intake (P = 0.03)
      predicted outcome, whereas normalized protein catabolic rate did not (P = 0.46).
      Multivariate analysis indicated that comorbidity (P = 0.0003) and age (P =
      0.0085) were the only independent predictors of outcome. The addition of plasma
      albumin and Kt/V increased the significance of the Cox model. Further analysis of
      comorbidity demonstrated the relative importance of vascular disease and left
      ventricular dysfunction. This study illustrates the profound influence of
      comorbid disease on mortality in continuous ambulatory peritoneal dialysis
      patients and suggests that it causes suppression of appetite independent of the
      dialysis dose.

PMID- 7645542
TI  - Glomerular macrophages in nephrotoxic serum nephritis are activated to oxidize
      low-density lipoprotein.
AB  - Studies were undertaken to investigate the hypothesis that infiltrating
      glomerular macrophages in experimental glomerulonephritis are activated to
      produce oxygen-free radicals that are capable of enhancing oxidation of low
      density lipoprotein (LDL). Low-density lipoprotein oxidation was assessed by
      increased electrophoretic mobility on agarose gel electrophoresis and by the
      generation of thiobarbituric acid-reactive substances. Lipoprotein uptake,
      degradation, and re-esterification by macrophages were assessed by measuring 14C
      oleic acid incorporation into cholesteryl oleate. Both peritoneal and glomerular
      macrophages have the ability to oxidize LDL to a form showing increased mobility
      on agarose gel electrophoresis. However, LDL incubated with glomerular
      macrophages underwent greater oxidation, resulting in increased generation of
      thiobarbituric acid-reactive substances (15.1 +/- 1.2 nmol malondialdehyde/mg LDL
      protein v 7.2 +/- 2.1 nmol malondialdehyde/mg LDL protein; P < 0.01). In
      addition, glomerular macrophages modified LDL to a form that greatly enhanced
      cellular synthesis of cholesteryl oleate compared with peritoneal macrophage
      modified LDL (30 +/- 11 pmol/10(6) cells/hr v 10 +/- 4 pmol/10(6) cells/hr; P <
      0.01). Superoxide dismutase, a scavenger of superoxide anion, inhibited
      macrophage-mediated oxidation of LDL. These results suggest that glomerular
      macrophages from nephritic rats are activated to modify LDL to a form avidly
      taken up by macrophage scavenger receptors. Thus, enhanced formation of oxidized
      LDL by infiltrating glomerular macrophages may contribute to glomerular injury in
      nephrotoxic serum nephritis.

PMID- 7645543
TI  - Sneddon's syndrome: a systemic arterio-occlusive disorder.
AB  - We describe a case of Sneddon's syndrome in a young woman with malignant
      hypertension and renal impairment. Kidney biopsy demonstrated intimal
      proliferation of small and medium-sized renal arteries similar to that seen in
      cutaneous arteries of patients with this syndrome. Ultrastructural examination
      showed the proliferated intima to be composed of smooth muscle fibers,
      fibroblasts, monocytes, and extensive deposition of dense granular and light
      staining amorphous materials. Our findings support the proposition that Sneddon's
      syndrome may not be simply a neurocutaneous vascular disorder as originally
      described, but rather a systemic arterioocclusive disorder with a variable
      clinical expression.

PMID- 7645544
TI  - Arsenic intoxication associated with tubulointerstitial nephritis.
AB  - Arsenic poisoning is an often unrecognized cause of renal insufficiency. We
      report a case of tubulointerstitial nephritis associated with an elevated urinary
      arsenic concentration. Removal of the putative source of arsenic resulted in
      symptomatic improvement, resolution of abnormal abdominal radiographs, and
      stabilization of renal function. This case emphasizes the importance of heavy
      metal screening in patients with multisystem complaints and tubulointerstitial
      nephritis.

PMID- 7645545
TI  - Infection of a subclavian venous stent in a hemodialysis patient.
AB  - Endovascular stent placement to prevent restenosis after angioplasty is being
      increasingly employed. A 63-year-old hemodialysis patient with a right forearm
      gortex graft developed ipsilateral arm edema, and a right subclavian vein
      stenosis was diagnosed. This vascular stenosis was presumably secondary to
      previous placement of temporary access catheters. The subclavian vein stenosis
      was treated with angioplasty, endovascular stenting, and warfarin, which resulted
      in resolution of the arm edema. Three weeks after stenting, the patient developed
      fever to 104 degrees F, chills, and right arm and shoulder edema. All blood
      cultures grew Staphylococcus aureus, and an Indium-labeled white blood cell scan
      was positive at the sight of the subclavian stent. Infectious disease consultants
      recommended urgent removal of the infected stent, but the extensive surgery
      required posed considerable risk of major morbidity. We elected to conservatively
      treat the patient. With loss of all upper-extremity access sites, the patient was
      converted to peritoneal dialysis. Despite the patient's ambulatory status, a
      femoral venous Hickman catheter was placed and tunneled through the abdominal
      subcutaneous soft tissue. The patient received 9 weeks of antibiotics by the
      Hickman catheter with an infusion pump, and warfarin was continued. There has
      been complete clinical resolution of infection and subclavian thrombosis.
      Endovascular stents are being used more commonly, and this is the first
      description, to our knowledge, of a stent infection. The stent infection was
      successfully managed without surgical removal.

PMID- 7645546
TI  - Apophysomyces elegans infection in a renal transplant recipient.
AB  - A 50-year-old cadaveric renal transplant recipient on immunosuppressive therapy
      is described with post-traumatic cutaneous infection caused by Apophysomyces
      elegans. He showed no evidence of hematogenous dissemination and recovered fully
      after therapy with extensive local debridement and amphotericin B lipid complex.
      An apparent drug-drug interaction between amphotericin B lipid complex and
      cyclosporine was encountered. The course of A elegans infection in transplant
      recipients may be similar to that described in immunocompetent hosts. A elegans
      infection should be considered in evaluation of post-traumatic cutaneous
      infection not readily responsive to antibacterial therapy.

PMID- 7645547
TI  - Antineutrophil cytoplasmic antibody-positive crescentic glomerulonephritis and
      thrombotic microangiopathy.

PMID- 7645548
TI  - The evaluation and selection of living kidney donors.
AB  - As the number of living kidney donations in the United States increases, it is
      important to continue to assess the manner in which potential living donors are
      evaluated and selected. Ethical issues can be framed using principles that are
      understandable to patients and physicians. Existing evidence suggests that, for
      most suitable donors, the short- and long-term risks of kidney donation are small
      enough to be outweighed by the potential benefits to the donor and recipient. A
      thorough but efficient evaluation of potential living donors, as outlined in this
      review, can effectively minimize the risks. However, mechanisms to provide long
      term follow-up of all living donors are still needed. Appropriate surveillance
      mechanisms not only will minimize any long-term risks to individuals who have
      already donated a kidney but will also provide the data needed to accurately
      assess the risk, however small, for future donors. With or without these data,
      living donations will likely continue to play an increasingly important role in
      renal transplantation.

PMID- 7645549
TI  - Evidence-based recommendations for the clinical use of recombinant human
      erythropoietin.
AB  - In an era of increasing scrutiny regarding use of health care resources, it is
      critical that physicians have rational, evidence-based guidelines for treatment
      decisions. This review of more than 200 published papers constitutes a
      comprehensive approach to evaluating the current evidence regarding the clinical
      use of recombinant human erythropoietin therapy in renal failure patients. After
      this review, specific recommendations are provided regarding who should receive r
      HuEPO; what the target hemoglobin should be; the best route of administration of
      r-HuEPO; how iron status should be evaluated and managed; and monitoring and
      follow-up of patients taking r-HuEPO. Throughout the article, areas for important
      future research are also identified.

PMID- 7645550
TI  - Developmental consequences of the renin-angiotensin system.
AB  - Molecular, cellular, and physiological studies indicate that the renin
      angiotensin system (RAS) is highly expressed during early kidney development. We
      propose that a major function of the RAS during early embryonic development is
      the modulation of growth processes that lead the primitive kidney into a properly
      differentiated and architecturally organized organ suited for independent
      extrauterine life. As development progresses, the RAS acquires new and
      overlapping functions such as the endocrine and paracrine regulation of blood
      pressure and renal hemodynamics. Disease states in adult mammals often result in
      expression of RAS genes and phenotypic changes resembling the embryonic pattern,
      emphasizing the importance of undertaking developmental studies. Because of their
      importance in health and disease, the immediate challenge is to identify the
      mechanisms that regulate the unique development of the RAS and its role(s) in
      normal and abnormal growth processes.

PMID- 7645552
TI  - Pattern of glomerular involvement in human immunodeficiency virus-infected
      patients: an Italian study.
AB  - Renal biopsy specimens from 26 adult human immunodeficiency virus (HIV)-infected
      patients with glomerular involvement were reviewed from the files of three
      hospital pathology services in Northern Italy. All the patients were Italian and
      most (19 of 26 patients) were intravenous drug addicts. The types of glomerular
      lesions were as follows: minimal-change glomerulopathy (two cases), mesangial
      proliferative glomerulonephritis (GN) with scanty immunoglobulin deposits (four
      cases), and various patterns of immune complex-mediated glomerulonephritis,
      including postinfectious GN (six cases), membranoproliferative GN (one case),
      membranous GN (three cases), immunoglobulin (Ig) A nephropathy (four cases), a
      mixed membranous and proliferative (three cases) and diffuse proliferative lupus
      like pattern with subendothelial deposits, and intraluminal thrombi (two cases)
      or subepithelial and subendothelial deposits (one case). None of the patients had
      evidence of HIV-associated nephropathy. Our study confirms previous observations
      on the low incidence of HIV-associated nephropathy among white HIV-infected
      patients in Europe, where immune complex-mediated GN seems to predominate. Apart
      from the frequent electron microscopic observation of endothelial tubuloreticular
      structures, none of the reported lesions could be distinguished on morphologic
      grounds from those occurring in uninfected patients. The high variability of the
      glomerular lesions upholds the need for accurate diagnosis for the clinician
      confronted with an HIV-positive patient with suspected glomerular involvement.

PMID- 7645551
TI  - Relationship between appearance of urinary red blood cell/white blood cell casts
      and the onset of renal relapse in systemic lupus erythematosus.
AB  - The purpose of the study was to determine the extent to which urinary sediment
      findings (changes in red blood cells [RBCs], white blood cells [WBCs], and the
      appearance of RBC and WBC casts) predict the onset of renal relapse (defined as a
      specific increase in proteinuria and/or serum creatinine level) in patients with
      systemic lupus erythematosus (SLE). Seventeen SLE patients with biopsy-proven
      diffuse proliferative glomerulonephritis at initial presentation were followed
      prospectively for 1,129 patient-months under a study protocol. Semiquantitative
      urinalyses were performed at 2-month intervals during periods with little or no
      SLE activity and, more frequently, during periods with increased SLE activity.
      Each urinalysis was accompanied by a clinical evaluation and a panel of screening
      tests relevant to the evaluation of SLE activity. During this study, 877
      semiquantitative urinalyses were performed and 43 renal relapses were observed in
      14 patients. No relapse occurred in three patients. Of the renal relapses, 30
      were defined as proteinuria relapses (mean baseline proteinuria increased from
      0.8 +/- 0.1 g/24 hr to 2.7 +/- 0.3 g/24 hr; P < 0.001) and 13 were defined as
      serum creatinine relapses (mean baseline serum creatinine increased from 2.7 +/-
      0.4 mg/dL to 3.8 +/- 0.5 mg/dL; P < 0.001). Red blood cell and/or WBC casts
      (cellular casts) were observed before or at the onset of 35 of the 43 renal
      relapses (sensitivity, 81%). The mean and median intervals between the appearance
      of cellular casts and the onset of renal relapse was 10 +/- 2 weeks and 8 weeks,
      respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7645553
TI  - Tetanus immunization and its association to hepatitis B vaccination in patients
      with chronic renal failure.
AB  - A defect in the immune response of patients with chronic renal failure leads to
      low response rates and insufficient antibody concentrations following a number of
      highly recommended vaccinations. This has been shown before for immunization
      against hepatitis B and influenza. Few data are available concerning the efficacy
      of vaccination with tetanus toxoid in these patients. In a prospective,
      controlled study we vaccinated seronegative patients with chronic renal failure
      not on dialysis, patients on chronic intermittent hemodialysis, and patients
      after kidney transplantation with tetanus toxoid. The results were compared with
      those of a control group consisting of 13 age-matched patients with mild
      essential hypertension and normal kidney function. Only 11 of 20 (55%) patients
      in the chronic renal failure group and 16 of 23 (69%) in the dialysis group had a
      protective antibody response after triple vaccination. In contrast, all the
      patients in the control group and six of seven transplant patients seroconverted.
      The response to tetanus toxoid was highly associated with the response to a
      previously administered vaccination against hepatitis B. Responders to this
      vaccination also had a better response rate to tetanus toxoid. The antibody
      concentrations after vaccination were lower in all patient groups compared with
      the controls; the lowest titers were found in the transplant patients. Therefore,
      renal patients will need revaccination much earlier, and tetanus toxoid antibody
      levels should be checked if a patient is injured and potentially requires
      vaccination.

PMID- 7645554
TI  - Hypertension in the hemodialysis population: a survey of 649 patients.
AB  - Accurate information on prevalence and status of blood pressure control among US
      hemodialysis patients is lacking. We have surveyed the status of blood pressure
      control in 649 hemodialysis patients (89.8% black) from 10 dialysis units in
      Mississippi. Our results show a hypertension prevalence of 72% (hypertension
      defined as mean arterial pressure prior to dialysis session > or = 114 mm Hg).
      This mean arterial pressure did not differ among black patients compared with
      white patients (P = 0.51). The majority of hypertensive patients (80%) had
      elevation of both systolic and diastolic blood pressure. Isolated systolic
      hypertension was present in only 20% of hypertensive patients and was not
      different between black and white patients (P = 0.10). Three hundred eighty-one
      patients (58.7% of the total population and 81.5% of the hypertensive patients)
      were receiving antihypertensives. Age was the only significant factor that
      correlated with blood pressure: older patients (> 65 years) had lower blood
      pressure (P < 0.0001). Race, time on dialysis, etiology of end-stage renal
      disease, adequacy of dialysis, and several excess volume parameters had no
      influence on the blood pressure level. Treated hypertensive patients had a
      predialysis mean blood pressure only 3 mm Hg less than the untreated hypertensive
      patients. No differences were found among four classes of antihypertensives with
      regard to the degree of blood pressure control. Patients with hypertension
      requiring more than one antihypertensive did not achieve a lower blood pressure
      than the untreated patients. There was no correlation between use of
      antihypertensives and the magnitude of decrease in blood pressure after
      dialysis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7645555
TI  - Vancomycin removal by high-flux polysulfone hemodialysis membranes in critically
      ill patients with end-stage renal disease.
AB  - To define the pharmacokinetics of vancomycin in patients undergoing maintenance
      hemodialysis in an acute care setting and to characterize the rebound phenomenon
      occurring after hemodialysis, vancomycin t1/2 during the interdialytic and
      intradialytic phases and intradialytic clearance were measured in eight
      critically ill patients undergoing high-flux hemodialysis using F-80 or F-60
      polysulfone dialyzers. Intradialytic clearance was determined using the recovery
      method. In patients dialyzed with F-80 dialyzers, interdialytic and intradialytic
      t1/2 for vancomycin were 162 +/- 69.8 hours and 4.7 +/- 1.3 hours, respectively.
      Intradialytic clearance was 108.5 +/- 16.3 mL/min, and 238 +/- 55 mg of
      vancomycin was recovered in the dialysate. In patients dialyzed with F-60
      dialyzers, interdialytic and intradialytic t1/2 were 211.0 +/- 166.8 and 4.6 +/-
      0.4 hours, respectively. Intradialytic clearance was 100.6 +/- 18.3 mL/min and
      the amount of vancomycin recovered was 252 +/- 79 mg. Vancomycin concentrations
      rebounded by 16% to 37% between 3 and 6 hours in patients dialyzed with the F-80
      dialyzer and 15% to 38% between 2 and 3 hours in patient dialyzed with F-60
      dialyzers. Hemodialysis with high-flux polysulfone dialyzers removes significant
      amounts of vancomycin in patients dialyzed in an acute care setting. A suggested
      scheme for vancomycin dosage adjustments in these patients is presented.

PMID- 7645556
TI  - Cross-sectional comparison of malnutrition in continuous ambulatory peritoneal
      dialysis and hemodialysis patients.
AB  - Although malnutrition is not uncommon in continuous ambulatory peritoneal
      dialysis (CAPD) and maintenance hemodialysis (MHD) patients, there has never been
      a large-scale comparison study of nutritional status with these two dialysis
      modalities. We therefore assessed protein-calorie nutrition in 224 CAPD patients
      and 263 MHD patients who were treated in eight centers in Italy. The CAPD
      patients were slightly older than the MHD patients (60.2 +/- 14.2 years v 56.3 +/
      15.1 years; P < 0.01), had undergone dialysis for less time (2.32 +/- 2.10 years
      v 3.66 +/- 2.66 years; P < 0.0001), and had higher residual renal function (1.83
      +/- 2.29 mL/min v 0.27 +/- 0.91 mL/min; P < 0.0001). Protein nitrogen appearance
      was 60.5 +/- 16.6 g/d and 61.9 +/- 16.5 g/d in the CAPD and MHD patients,
      respectively. In CAPD versus MHD patients, serum total protein and albumin tended
      to be lower; serum transferrin and midarm muscle circumference were similar; and
      relative body weight, skinfold thickness, and estimated percent body fat tended
      to be greater. These greater values in CAPD patients were particularly evident in
      those who were 65 years of age or older. Serum glucose, total cholesterol, and
      triglycerides also were greater in CAPD patients. The subjective global
      nutritional assessment indicated a significantly greater proportion of
      malnourished CAPD patients than MHD patients (42.3% v 30.8%). The greater
      prevalence of malnutrition in CAPD patients diminished with age. Maintenance
      hemodialysis patients older than 76 years were more likely to be malnourished
      than CAPD patients. In patients less than 65 years of age, protein-calorie
      malnutrition was more likely to be present in CAPD patients than in MHD patients.

PMID- 7645557
TI  - Late withdrawal of cyclosporine in stable renal transplant recipients.
AB  - The use of cyclosporine (CsA) in renal transplantation has been associated with
      an improvement in 1-year graft survival, but has not changed the rate of late
      graft loss. We sought to determine whether the intent to withdraw CsA late after
      renal transplantation affects renal transplant survival and whether there is a
      racial difference in the effect of CsA withdrawal. This retrospective study
      included 384 consecutive patients receiving a renal transplant during the 1984 to
      1991 period who were treated with CsA/azathioprine/prednisone and who had a
      functioning allograft 6 months following transplantation. Of these, 97 were
      electively withdrawn from CsA at a median of 22 months following transplantation.
      Factors significantly associated with the decision to withdraw CsA included white
      race, older age, and lower serum creatinine. Acute rejection within 6 months of
      stopping CsA occurred in 12 patients (12.4%), including nine of 78 (11.5%) white
      patients and three of 19 (15.8%) black patients. For the group of 287 patients
      who were not withdrawn from CsA, the 6-year graft survival rate was 59% (95%
      confidence interval, 52%, 66%). For the group of patients taken off of CsA, the 6
      year graft survival rate was 84% (95% confidence interval, 76%, 92%). Cox
      proportional hazard survival analysis indicated that the intent to discontinue
      CsA was associated with better graft survival, with a hazard ratio of 0.37 (95%
      confidence interval, 0.20, 0.70), independent of other variables that may affect
      graft survival. A separate analysis controlling for waiting time bias also
      favored the CsA withdrawal group. There was no detectable racial difference in
      the effect of CsA withdrawal on graft survival.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7645559
TI  - Effect of lovastatin on the development of polycystic kidney disease in the
      Han:SPRD rat.
AB  - Proliferation of tubular epithelial cells is a major element leading to cyst
      formation in Han:SPRD rats with autosomal dominant polycystic kidney disease
      (PKD). ras proteins are important in the control of renal cell proliferation, and
      ras gene expression is increased in PKD. Farnesyl pyrophosphate, an intermediate
      in the conversion of acetyl-CoA to cholesterol, is required for the activation of
      ras guanosine triphosphate (GTP)-binding proteins that are important in the
      execution of several cellular functions, including cell proliferation. 3-Hydroxy
      3-methyl-glutaryl coenzyme A reductase inhibitors, such as lovastatin, reduce
      farnesyl production in responsive cells and thereby have potential for
      ameliorating the accelerated epithelial cell proliferation of PKD. We
      administered lovastatin to heterozygous (Cy/+) Han:SPRD rats (4 mg/kg/d
      subcutaneously) from age 4 to 10 weeks, a period of rapid cystic disease
      progression in these animals. Untreated male Cy/+ rats developed larger cystic
      kidneys and had more severe renal functional impairment than females, as reported
      previously. In males, lovastatin significantly decreased cystic kidney size
      (referenced to body weight), the volume density of cysts, and the serum urea
      nitrogen level 14.5%, 24.4%, and 25.6/%, respectively. The corresponding changes
      in females were insignificant, and lovastatin had no effect on kidney weight or
      serum urea nitrogen in homozygous (+/+) normal male animals. On the basis of
      these results we conclude that lovastatin diminishes the severity of PKD in
      heterozygous male Han:SPRD rats.

PMID- 7645558
TI  - Enalapril treatment of posttransplant erythrocytosis: efficacy independent of
      circulating erythropoietin levels.
AB  - To determine the mechanism of action by which angiotensin-converting enzyme (ACE)
      inhibitors lower hematocrit in patients with posttransplant erythrocytosis,
      indices of red blood cell production and red blood cell destruction were obtained
      serially for 6 months from 10 renal transplant patients receiving treatment with
      enalapril for this problem. Before treatment, five patients had an elevated red
      blood cell mass, four had plasma volume contraction, and one had both. The mean
      hemoglobin concentration decreased by 2 g/dL (range, 0.5 to 3.3 g/dL), from 17 +/
      1 g/dL to 15 +/- 1 g/dL (P = 0.001) following 6 months of enalapril therapy.
      Similarly, the mean hematocrit decreased by 8% (range, 3% to 12%), from 52% +/-
      2% to 44% +/- 3% (P = 0.001) during the same period. The mean reticulocyte count
      tended to decrease, although the change was not significant. The red blood cell
      mass decreased dramatically by 15% to 50%, from 32 +/- 9 mL/kl to 23 +/- 4 mL/kg
      (P = 0.008). Although serial erythropoietin levels declined steadily in two
      patients, there was no consistent change in the other patients. Mean levels
      decreased modestly, from 20 +/- 11 mU/mL at baseline to 12 +/- 5 mU/mL at 6
      months, a change that was not statistically significant. Mean levels at each time
      point were not statistically different from the mean pretreatment value.
      Furthermore, during enalapril therapy, there was no correlation between mean
      circulating erythropoietin level and mean hematocrit (r = 0.43, P = 0.20) or
      hemoglobin concentration (r = 0.36, P = 0.30) or between changes in these
      parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7645560
TI  - Acute renal failure after streptokinase therapy in a patient with acute
      myocardial infarction.
AB  - Cholesterol embolization syndrome (CES) usually occurs after the performance of
      invasive vascular procedures. With the frequent use of thrombolytic agents, an
      increasing number of reported cases of renal CES attributed to the use of such
      agents has appeared. In most of these reports, the diagnosis was made on the
      basis of either clinical presentations or skin biopsy. We report a patient who
      developed acute renal failure as a result of histologically proven renal CES
      occurring after the use of streptokinase for the treatment of an acute myocardial
      infarction. The acute renal failure later became chronic; consequently, the
      patient was placed on continuous ambulatory peritoneal dialysis. Although the
      prognosis of renal CES has been described to be poor, our patient regained enough
      of his renal function 8 months after the onset of renal failure to make it
      possible to discontinue the dialytic therapy.

PMID- 7645562
TI  - Renal vasculitis associated with ciprofloxacin.
AB  - We report two patients treated with ciprofloxacin who presented with acute renal
      failure. On renal biopsy, a necrotizing vasculitis was identified in addition to
      acute interstitial nephritis. Improvement in renal function resulted with the
      discontinuation of the antibiotic and the institution of immunosuppressive
      therapy.

PMID- 7645561
TI  - A combination of livedo racemosa, occlusion of cerebral blood vessels, and
      nephropathy: kidney involvement in Sneddon's syndrome.
AB  - A 59-year-old woman with retinal vein thrombosis and livedo racemosa had
      hematuria (4+) and proteinuria (1.7 g/day). Skin biopsy showed swollen blood
      vessel walls with infiltration of mononuclear cells, which were compatible with
      livedo racemosa (vasculitis). Magnetic resonance imaging (MRI) of the brain
      demonstrated multiple lacunar infarctions in the basal ganglia and white matter.
      Renal biopsy showed that small round cells had infiltrated into the interstitium,
      and a reticular structure was observed in the glomerular hilus. An amorphous
      substance composed of a single cell was present in the glomerular capillary
      lumen. Immunofluorescent study demonstrated the deposition of only IgA, in a
      segmental pattern differing from the diffuse global mesangial pattern seen in IgA
      nephropathy. After combined therapy including 40 mg/day prednisolone, 50 mg/day
      cyclophosphamide, antiplatelet drug, and anticoagulant was started, proteinuria
      and hematuria improved to 0.5 g/day and 2+, respectively, at the time of
      discharge. Sneddon's syndrome is a rare entity characterized by livedo racemosa
      and cerebrovascular lesions. In our patient with livedo racemosa, occlusion of
      cerebral blood vessels, and nephropathy with segmental immunoglobulin A (IgA)
      deposition, no antiphospholipid antibodies were detected on routine examination.
      Dermatologists, neurologists, psychiatrists, and nephrologists should be aware of
      the existence of Sneddon's syndrome with nephropathy (LI-O-N).

PMID- 7645563
TI  - Identification of selective immunoglobulin a deficiency by renal biopsy.
AB  - We report three cases of selective immunoglobulin A (IgA) deficiency in which
      lack of direct immunofluorescent staining for IgA on renal biopsy specimens
      contributed to the diagnosis. In two patients, one with systemic lupus
      erythematosus and the other having asthma with nephrotic syndrome, the diagnosis
      of IgA deficiency was suggested by the complete absence of IgA on the renal
      biopsy. In the third patient, a renal transplant recipient, initial biopsies
      demonstrated donor-derived IgA, which disappeared on subsequent biopsies. The
      diagnosis of IgA deficiency was confirmed in all three patients by serologic
      quantification of IgA.

PMID- 7645564
TI  - Glomerular disease and lung transplantation.
AB  - Three patients with lung or heart/lung transplants developed nephrotic-range
      proteinuria 2 to 5 years posttransplantation. Kidney biopsy showed focal
      segmental glomerulosclerosis in two patients and probable focal sclerosis in the
      third. A retrospective review of postmortem kidney specimens from 18 lung
      transplant recipients who died did not indicate additional cases of glomerular
      disease. The three patients with glomerular disease after lung transplantation
      had very few clinical similarities other than nephrotic-range proteinuria and
      lung transplantation. Their underlying lung diseases were different, and their
      posttransplantation courses were very different in terms of pulmonary function,
      cyclosporine nephrotoxicity, and other complications. We did not find in the
      literature previous reports of de novo focal segmental glomerulosclerosis or
      other glomerular lesions after lung transplantation. We suspect that additional
      cases will be identified in the future.

PMID- 7645565
TI  - Minimal-change nephrotic syndrome after cyclosporine withdrawal in a marrow
      transplant recipient.

PMID- 7645566
TI  - Glomerular thrombosis predicts progression of glomerulonephritis: can we prevent
      progression?
AB  - The evidence for the important role of coagulation in the genesis and
      perpetuation of glomerular injury in diffuse proliferative lupus
      glomerulonephritis is reviewed. The importance of early detection is emphasized,
      so that treatment can be started before irreversible glomerular injury has
      occurred. Urinalysis and simple tests of renal function are effective means of
      early detection.

PMID- 7645567
TI  - New insights into circulating cell-endothelium interactions and their
      significance for glomerular pathophysiology.
AB  - Neutrophil and monocyte infiltration of kidney glomeruli is a striking pathologic
      finding in the early stages of most forms of glomerulonephritis and appears to be
      an important determinant of glomerular injury. Recent research has permitted to
      clarify the mechanisms of leukocyte trafficking to inflamed glomeruli, which
      appear to involve several coordinated steps: chemotaxis along a concentration
      gradient of chemoattractants, adhesion to endothelial cells, diapedesis between
      endothelial cells, and interaction with resident renal cells. In
      glomerulonephritis, the deposition of immune complexes within glomerular
      capillaries triggers the local synthesis of chemotactic factors, including
      complement fragments, platelet-activating factor, leukotrienes, interleukin-8,
      and monocyte chemotactic protein-1, which promote attraction of neutrophils and
      monocytes within the glomerular tuft. Adhesion to resident glomerular cells, a
      critical step in the process of leukocyte infiltration, is a dynamic process that
      results from opposite factors: (1) shear forces generated by the movement of
      blood within the glomerular microcirculation that tend to detach inflammatory
      cells from the vascular wall and (2) adhesion glycoproteins expressed on the
      surface of leukocytes and endothelial cells, which are upregulated in human and
      experimental glomerulonephritis. It has been proposed that P-selectin, which is
      rapidly expressed on the surface of endothelial cells exposed to various stimuli,
      is a principal mediator of initial low-affinity binding of leukocytes (rolling).
      The tethering component mediated by P-selectin facilitates interaction of
      leukocytes with platelet-activating factor, a biologically active phospholipid
      that is rapidly synthesized by activated endothelial cells and is coexpressed
      with P-selectin on the endothelial cell plasma membrane.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7645568
TI  - Rinsing time and disinfectant release of reused dialyzers: comparison of
      formaldehyde, hypochlorite, warexin, and renalin.
AB  - The influence of disinfecting agent (DA) type on the rinsing time of reused
      dialyzers and DA rebound release after rinsing is unknown. We compared 10 groups
      of five dialyzers each: cellulose acetate capillaries and AN69 plates disinfected
      with formaldehyde (F), polysulfone and cuprophane capillaries disinfected with
      3.5% Renalin (R; Renal Systems, Minneapolis, MN), polysulfone capillaries and
      AN69 plates disinfected with 0.5% R, and AN69 capillaries and plates disinfected
      with Hypochlorite (H; Solvay, Brussels, Belgium) or Warexin (W; Guardian
      Chemical, Division of United Guardian Inc, Hauppage, NY), respectively.
      Formaldehyde, R, H, and W were detected by standard tests. The rinsing time
      required to reach undetectable levels of DA is shortest for H and W, intermediate
      for R 0.5% and 3.5%, and longest for F (F v R, H, and W; R v H and W; and H v W:
      P < 0.001). The rebound release 30 minutes after completion of rinsing is the
      highest for F (average 6 ppm), intermediate for R 0.5% and 3.5% (mean 1.4 ppm, P
      < 0.002 compared with F and mean 2.95 ppm, P < 0.05 compared with F,
      respectively), and low (< or = 1 ppm) for W and H (P < 0.001 compared with F and
      P < 0.01 compared with R 3.5% and 0.5%). We conclude that the dialyzer rinsing
      time needed to obtain undetectable levels of DA depends on the DA type. In
      addition, we demonstrate that like F, R is released from reused dialyzers after
      "adequate rinsing." The potential clinical consequences of this phenomenon
      require further investigation.

PMID- 7645570
TI  - Recertification: a challenge to those trained in the "good old days".

PMID- 7645569
TI  - The American Board of Internal Medicine recertification program--nearing liftoff.

PMID- 7645571
TI  - Another method for correcting metabolic alkalosis.

PMID- 7645572
TI  - An evaluation of scheduled bright light and darkness on rotating shiftworkers:
      trial and limitations.
AB  - The effectiveness of a program of scheduled bright light and dark to alter the
      circadian pacemakers of rotating shiftworkers were evaluated. Thirteen industrial
      workers were exposed to scheduled bright light of 6,000-12,000 lux on at least
      half of their 12-hr night shifts for 3 months, as well as ambient light of 1,200
      1,500 lux. All 10 workers evaluated with urinary melatonin levels had morning
      melatonin suppression on the night shift, and 50% had a statistically significant
      circadian change. Although a few significant changes were noted concerning
      reported sleep and alertness, most findings concerning self-perceived alertness
      and performance at work, and sleep patterns were mixed and inconsistent. The
      major complaint was increased difficulty adjusting to being off work after the
      night shift during the light phase. The alteration in urinary melatonin levels is
      the first objective demonstration that the bright light technology can alter the
      circadian pacemakers of workers in an industrial setting. At this worksite, a
      number of interventions to lessen the effects of rotating shiftwork are being
      evaluated. Criteria are proposed that should be considered in evaluating a
      worksite for the use of bright light technology.

PMID- 7645573
TI  - Work-related musculoskeletal symptoms among sheet metal workers.
AB  - We report results of two pilot studies of the relationship between
      musculoskeletal disorders and work tasks in sheet metal workers. These two
      studies were undertaken as pilot investigations to determine if symptoms of
      carpal tunnel syndrome or other work-related musculoskeletal symptoms are present
      in sheet metal workers, and to determine if we could begin to identify the
      factors in sheet metal work that cause them. In the first study, telephone
      interviews were conducted with 18 disabled sheet metal workers; the second survey
      entailed self-administered questionnaires completed by 47 active and retired
      sheet metal workers. Among the disabled workers, rotator cuff cases reported the
      greatest percent of time spent hanging duct, an overhead task commonly carried
      out during field work. Carpal tunnel cases reported more hand tool use than the
      rotator cuff cases. The questionnaire survey of active and retired workers found
      the proportion of time spent in a sheet metal shop (contrasted with field work)
      to be positively associated with hand symptoms; sheet metal workers who spent at
      least 65% of their time in the shop had an odds ratio of 3.4 for symptomatic hand
      cumulative trauma disorder (CTD) (p = 0.12). The proportion of time spent hanging
      duct was positively associated with both neck and shoulder symptoms, with odds
      ratios of 7.9 (p = 0.08) and 2.7 (p = 0.16), respectively.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7645574
TI  - A detailed analysis of work-related injury among youth treated in emergency
      departments.
AB  - Telephone interviews were conducted with 146 14- to 16-year-olds who incurred an
      occupational injury treated in an emergency department during the period July
      through September 1992. Thirty-two percent of the injuries occurred as the result
      of using equipment. Over half the workers reported not having received prior
      training on how to avoid injury. The injury limited normal activities for at
      least 1 day for 68% of the youth and for more than a week for 25%, corresponding
      to an estimated 6,208 (95% CI: 4,277, 8,139) and 2,639 (95% CI: 1,580, 3,699)
      youths nationwide, respectively. Employment in retail trades, equipment use, lack
      of training, and burn injuries were associated with increased limitation of
      normal activities. Nineteen percent of the youths appear to have been injured in
      jobs declared to be hazardous, or typically prohibited for their age (14- and 15
      year-olds) under federal child labor laws. The prohibited job directly
      contributed to the injury in 64% of these cases.

PMID- 7645575
TI  - Work outcome in workers with occupational skin disease.
AB  - We carried out a follow-up study of employment outcome for 230 workers with a
      diagnosis of occupational skin disease who were at least 2 years postdiagnosis.
      Seventy-eight percent of the workers were working, but 57% of those working had
      changed jobs, 67% because of their skin problem. Thirty-one percent had lost no
      time from work because of their skin disease, while 35% had lost at least 1
      month. Forty-three percent had applied for workers' compensation benefits, and
      87% of those who had applied were successful in their claims. Older workers were
      more likely to be unemployed and to have applied for workers' compensation
      benefits. Women were less likely to have lost time from work and to have applied
      for workers' compensation. Those who had changed their jobs tended to have a
      better outcome with respect to active dermatitis, though they had lost more time
      from work and had more often applied for workers' compensation benefits.

PMID- 7645576
TI  - United States non-Hodgkin's lymphoma surveillance by occupation 1984-1989: a
      twenty-four state death certificate study.
AB  - Death certificates from 23,890 male and female non-Hodgkin's lymphoma (NHL) cases
      and 119,450 noncancer controls from 24 states for the period 1984-1989 were used
      to generate hypotheses regarding occupational associations. Cases were frequency
      matched by age, race, and gender with five controls per case. Odds ratios were
      calculated for 231 industries and 509 occupations. Significant associations were
      observed for a variety of white-collar professionals (i.e., real estate agents,
      secretaries, bookkeepers, teachers, postal employees, business agents, engineers,
      chemists, and medical professionals) and blue-collar occupations (i.e.,
      firefighters, farm managers, aircraft mechanics, electronic repairers, mining
      machine operators, and crane and tower operators).

PMID- 7645577
TI  - Unbiased vs. conservative estimators of etiological fractions: examples of
      misclassification from studies of occupational lung cancer.
AB  - Theoretical studies emphasize the importance of making unbiased etiological
      fraction estimates. In empirical works, however, the published estimates are
      usually conservative. The purpose of the present report is to study, empirically,
      the numerical magnitude of such conservative biases. Examples from the literature
      on occupational exposure and lung cancer are reported. It is demonstrated that
      conservative bias may decrease a numerical estimate by more than a factor 10 and
      that decreases by a factor 2 or 3 are not unusual. It is concluded that it is
      important, in future review studies, to pay attention to the magnitude of the
      conservative biases in the published empirical estimates and to put most emphasis
      on the least biased estimates in the review process.

PMID- 7645578
TI  - Respiratory symptoms and lung function in wool textile workers.
AB  - Our study investigated a group of 216 wool textile workers (158 women and 58
      men). Respiratory symptoms were assessed by questionnaire in wool textile workers
      and in 130 not exposed (control) workers. Ventilatory capacity was measured in
      wool workers by recording maximum expiratory flow-volume (MEFV) curves on Monday
      before and after the work shift. Forced vital capacity (FVC), 1-second forced
      expiratory volume (FEV1), and flow rates at 50% and the last 25% of the vital
      capacity (FEF50, FEF25) were measured on the MEFV curves. Analysis of the data
      demonstrated a significantly higher prevalence of all chronic respiratory
      symptoms in wool workers than in controls, being the highest in wool workers for
      nasal catarrh (M: 63.8%; F: 44.9%) and for sinusitis (M: 62.1%; F: 43.0%). A high
      prevalence of acute symptoms, associated with the work shift, was also noted in
      wool workers. Exposure to wool dust caused significant across-shift reductions of
      ventilatory capacity varying from 1.4% for FEV1 to 9.1% for FEF50. Textile
      workers exposed to wool for > 10 years in the workplace had similar across-shift
      reductions of ventilatory capacity tests as those with shorter exposures. In a
      large number of these wool workers, FEF50 and FEF25 were below 70% of predicted
      normal values. Smokers had acute and chronic lung function changes similar to
      those of nonsmokers, indicating that smoking did not account for all the
      respiratory effects seen in wool processing workers. Our data suggest that dust
      exposures in wool textile mills may be associated with the development of chronic
      respiratory symptoms and impaired lung function.

PMID- 7645580
TI  - Potential genotoxic risk related to simultaneous exposure to radionuclides and
      cytostatics.
AB  - The aim of the study was to evaluate the genotoxic risk to medical personnel
      concurrently exposed to ionizing radiation and antineoplastics, using changes in
      their lymphocyte cell genome as a bioindicator. The study comprised 12 female
      nurses employed in the nuclear medicine hospital department and an equal number
      of matched controls. For each examinee, both conventional structural chromosomal
      aberration analysis and sister chromatid exchange test (SCE) were carried out.
      According to Student's t-test, neither the incidence of structural chromosomal
      aberrations (p > 0.6) nor the mean SCE-frequency rate (p > 0.3) were
      significantly increased among the exposed subjects. Nevertheless, in those
      exposed, irreparable chromosomal damages and wide SCE-ranges were observed. Such
      findings suggest the possibility of genotoxic implications of concurrent
      occupational exposure to ionizing radiation and antineoplastic drugs.

PMID- 7645579
TI  - Airway responsiveness to methacholine, respiratory symptoms, and dust exposure
      levels in grain and flour mill workers in eastern France.
AB  - Our goal was to assess the relation between dust exposure levels and the
      respiratory health status of workers in grain and flour mills in eastern France.
      We studied 118 male workers from 11 mills and 164 unexposed male controls. Dust
      concentration was measured by personal sampling methods. Outcome variables
      included respiratory symptoms, routine pulmonary function tests, and indices of
      airway responsiveness to methacholine. A great within- and between-area
      variability of inhalable dust concentration was found in all mills. A dose
      response relationship was observed between dust exposure levels and chronic
      respiratory symptoms, suggesting that exposure to grain and flour dust may lead
      to chronic bronchitis. A significant relation was found between dust exposure and
      airway hyper-responsiveness; this finding is important since it has been
      hypothesized that the latter abnormality may lead to or be a predisposing factor
      in subsequent chronic, irreversible airflow obstruction.

PMID- 7645581
TI  - Decreases of CD4- and CD8-positive T lymphocytes in retired chromate workers.
AB  - To investigate the effects of chromates on the human immune system, we measured
      total T lymphocytes and their two major subpopulations (CD4+ and CD8+ T
      lymphocytes) in the peripheral blood of 19 retired male workers who had been
      exposed to chromate at a chemical plant. The results indicated that both CD4+ and
      CD8+ T lymphocytes were significantly decreased, resulting in decreases in total
      T lymphocytes and total lymphocytes.

PMID- 7645582
TI  - Effect of lead on blood pressure in occupationally nonexposed men.
AB  - To determine if low-level exposure to lead has an effect on arterial blood
      pressure, demographic and clinical data of a group of 507 males without any
      occupational exposure to lead were analyzed in a retrospective study. The
      following variables were included in the analysis: age, height, weight, nicotine
      consumption, alcohol intake, blood lead, systolic blood pressure, diastolic blood
      pressure, and erythrocyte count. The effects of the variables age, weight,
      height, alcohol intake, nicotine consumption, and blood lead on blood pressure
      were investigated by stepwise linear regression analysis. The diastolic as well
      as the systolic blood pressure was significantly influenced by Body Mass Index,
      age, and alcohol. A significant effect of lead could be found only for diastolic
      blood pressure. None of the possible interactions were significant enough to
      merit inclusion in the statistical model. Regarding the strength of the effects
      on diastolic blood pressure we find that lead ranks after age, weight. In
      conclusion, this study shows that lead has an effect on diastolic arterial blood
      pressure in a survey of a group of middle-aged, occupationally nonexposed men.

PMID- 7645583
TI  - Pancreatic cancer in workers at a transformer manufacturing plant.

PMID- 7645584
TI  - Cancer mortality at a transformer manufacturing plant: cohort construction and
      analysis.

PMID- 7645585
TI  - Frontometaphyseal dysplasia: neonatal radiographic diagnosis.
AB  - Frontometaphyseal dysplasia (FMD) is an uncommon genetic syndrome affecting bone
      and connective tissue. This condition is characterized by hyperostosis of the
      skull and prominence of the supraorbital ridges; long bones have flared
      metaphyses. Frontometaphyseal dysplasia is an X-linked dominant trait with more
      severe manifestations in males and with extreme variability in females. Diagnosis
      in the neonatal period is difficult. We present 2 newborn boys with the
      radiographic findings of FMD.

PMID- 7645586
TI  - Lipoma of corpus callosum associated with dysraphic lesions and trisomy 13.
AB  - We report on a further case of corpus callosal lipoma and frontal cranial
      defects. Most cases in the literature of corpus callosal lipoma in association
      with "dysraphic" lesions have been frontal in location. Malformation of the
      corpus callosum is said to be associated with 50% of these lipomas. Trisomy 13
      was confirmed by the 13q14 cosmid probe on paraffin-embedded liver tissue.

PMID- 7645587
TI  - Parental origin of the extra haploid chromosome set in triploidies diagnosed
      prenatally.
AB  - The parental origin of the additional chromosome complement in a total of 17
      cases of triploidy was determined mainly using highly polymorphic
      microsatellites. Maternal origin of the triploidy was demonstrated in most cases.
      To the best of our knowledge, this is the first systematic evaluation of the
      parental origin of chromosome sets in fetuses who survived until a cytogenetic
      diagnosis was established. In contrast to previous investigations this study
      documented a predominance of maternal origin of the extra haploid set mainly due
      to longer survival time for digynic triploidies. The concept of 2 distinct fetal
      phenotypes in triploidy is clearly supported by this study.

PMID- 7645588
TI  - Spectrum of X-linked hydrocephalus (HSAS), MASA syndrome, and complicated spastic
      paraplegia (SPG1): Clinical review with six additional families.
AB  - X-linked hydrocephalus (HSAS) (MIM *307000), MASA syndrome (MIM *303350), and
      complicated spastic paraplegia (SPG1) (MIM *312900) are closely related. Soon
      after delineation, SPG1 was incorporated into the spectrum of MASA syndrome. HSAS
      and MASA syndrome show great clinical overlap; DNA linkage analysis places the
      loci at Xq28. In an increasing number of families with MASA syndrome or HSAS,
      mutations in L1CAM, a gene located at Xq28, have been reported. In order to
      further delineate the clinical spectrum, we studied 6 families with male patients
      presenting with MASA syndrome, HSAS, or a mixed phenotype. We summarized data
      from previous reports and compared them with our data. Clinical variability
      appears to be great, even within families. Problems in genetic counseling and
      prenatal diagnosis, the possible overlap with X-linked corpus callosum agenesis
      and FG syndrome, and the different forms of X-linked complicated spastic
      paraplegia are discussed. Since adducted thumbs and spastic paraplegia are found
      in 90% of the patients, the condition may be present in males with nonspecific
      mental retardation. We propose to abandon the designation MASA syndrome and use
      the term HSAS/MASA spectrum, incorporating SPG1.

PMID- 7645589
TI  - MIDAS syndrome respectively MLS syndrome: a separate entity rather than a
      particular lyonization pattern of the gene causing Goltz syndrome.

PMID- 7645590
TI  - Lethal multiple pterygium syndrome: importance of fetal physical examination.

PMID- 7645591
TI  - Uniparental isodisomy 13 in a normal female due to transmission of a maternal
      t(13q13q).
AB  - Chromosomes from a normal 23-year-old, primigravid woman were examined at 10
      weeks of gestation because of her mother's history: 8 miscarriages and two
      liveborn infants (the proposita and a brother who died at 3 days with multiple
      anomalies). Karyotypes of the proposita and her normal mother were
      45,XX,t(13q13q). No evidence of mosaicism was encountered. When the proposita
      inherited the t(13q13q), she received two copies of 13q from her mother.
      Moreover, she and her mother shared the same homozygous pattern of alleles from 7
      highly polymorphic microsatellite repeats localized along 13q. No evidence of
      paternal markers from 13 was detected, although biparental inheritance was
      demonstrated with DNA markers from chromosomes 2 and 17. Cytogenetic and
      molecular findings indicated that the proposita's chromosomal complement included
      mUPD 13q. The proposita's normal phenotype suggested that no maternally imprinted
      genes map to 13q.

PMID- 7645592
TI  - Rieger syndrome with de novo reciprocal translocation t(1;4) (q23.1;q25).
AB  - We report on a boy with Rieger syndrome, who had an apparently balanced
      reciprocal translocation between chromosomes 1 and 4. The clinical manifestations
      of this patient were characterized by irregular shaped pupils with a prominent
      Schwalbe line and an umbilical hernia. On cytogenetic studies, he was found to
      have a de novo reciprocal translocation 46,XY,t(1;4) (q23.1;q25), without visible
      deletion. His parents had normal chromosomes. A review of both cytogenetic and
      genetic linkage analyses with Rieger syndrome showed that chromosome 4q was
      involved. This and other previous reports suggested that the gene for Rieger
      syndrome is mapped to the 4q25-->4q26 segment adjoining the breakpoint.

PMID- 7645593
TI  - Absent pituitary gland in two brothers with an oral-facial-digital syndrome
      resembling OFDS II and VI: a new type of OFDS?
AB  - The oral-facial-digital syndromes (OFDS) comprise a group of heterogeneous
      genetic disorders. Considerable clinical overlap exists within the nine described
      types [Toriello, Clin Dysmorph 2:95-105, 1993], and with other entities such as
      Pallister-Hall (PH) syndrome and hydrolethalus syndrome, leading to difficulties
      in the classification of OFDS. We report on two brothers with findings
      overlapping OFDS II, VI, and Pallister-Hall syndrome who had congenital absence
      of the pituitary gland. This may represent a new type of OFDS or, alternatively,
      an example of phenotypic variability within the OFDS. It also emphasizes that
      agenesis of the pituitary gland can occur in a variety of syndromes with midline
      defects.

PMID- 7645594
TI  - Familial occurrence of patent ductus arteriosus.
AB  - We describe 7 relatives with patent ductus arteriosus (PDA) and a slightly
      unusual facial appearance with prominent midface with nose elongation and
      flattening of the nasal bridge, wide-set eyes, downturned palpebral fissures,
      mild ptosis, thickened lips, and apparently slightly low-set ears. Autosomal
      dominant inheritance is suggested in this family. Other families where affected
      members have PDA and a similar facial appearance and autosomal dominant
      inheritance were described previously by Char [1978: BD:OAS XIV (6B):303-305] and
      Temple [1992: Clin Dysmorphol 1:17-21].

PMID- 7645595
TI  - Use of fluorescence in situ hybridization to clarify a complex chromosomal
      rearrangement in a child with multiple congenital anomalies.
AB  - A child with multiple congenital anomalies was referred for cytogenetic
      evaluation. G-banded analysis showed a complex chromosome rearrangement involving
      6 different chromosomes and 10 breakpoints. Fluorescence in situ hybridization
      (FISH) using whole chromosome painting probes and repetitive sequence probes was
      performed. In most cases the painting probes alone helped to clarify the G-banded
      results. However, in one instance, where the terminal band of the long arm of
      chromosome 1 was involved, the use of a telomeric probe was essential in defining
      the rearrangement.

PMID- 7645596
TI  - Outcome of Sturge-Weber syndrome in 52 adults.
AB  - Sturge-Weber syndrome (SWS) is a neurocutaneous disorder characterized by
      cutaneous facial angioma, leptomeningeal angioma associated with seizures and
      other neurologic complications including mental retardation, and glaucoma. Only
      limited information about long-term outcome, including the societal integration
      of adult patients, is available in the literature. Data on 52 adults with SWS,
      ages 18-63 years, ascertained through the Sturge-Weber Foundation, were obtained
      via written questionnaires, telephone interviews, and reviews of medical records.
      The distribution of port-wine stains (cranial 98%, extracranial 52%) and the
      prevalences of glaucoma (60%), seizures (83%), neurologic deficit (65%), and
      other complications were established. The age of onset of glaucoma (0-41 years),
      the age of onset of seizures (0-23 years), and the correlation between the
      distribution of port-wine stains and the prevalence of seizures was identified.
      The relationship between the age of onset of seizures and seizure control was
      established. In those with and without seizures, the prevalences of developmental
      delay (43% vs. 0%), emotional and behavior problems (85% vs. 58%), special
      education requirements (71% vs. 0%), and employability (46% vs. 78%) were
      analyzed. Overall, 39% were financially self-sufficient, and 55% were or could be
      married. Ten participants produced 20 liveborn offspring; 17 were healthy, and
      tuberous sclerosis, a cafe-au-lait spot, and a "birthmark" were found in 1 child
      each. The results of this study can be used for genetic counseling in Sturge
      Weber syndrome.

PMID- 7645597
TI  - Exploration of the effects of predictive testing for Huntington disease on
      intimate relationships.
AB  - The focus in predictive testing for Huntington disease is beginning to shift from
      individuals at risk to an examination of the effects on other relatives,
      particularly on spouses and partners. We examine the effects of participating in
      a predictive testing program for 25 couples. When assessed prior to testing,
      spouses were significantly more depressed than their at-risk partners. After
      pretest counseling, 6 (24%) of the couples chose not to pursue testing. At
      baseline, these 6 couples had significantly higher levels of psychological
      distress and marital dysfunction than couples who did choose to complete testing.
      Of the 19 couples completing testing, 5 received an increased risk result and 14
      received a decreased risk result. Prior to testing, the partners of individuals
      who later received an increased risk result exhibited higher levels of marital
      distress. At 3- and 6-month follow-ups, high-risk couples were significantly more
      distressed than low-risk couples. These levels of distress improved somewhat at 9
      months after testing, but began to climb again at 12 months. Individuals at
      increased risk were significantly more distressed at all points during follow-up
      as compared to individuals at low risk. No significant differences were found
      between the partners of high- and low-risk individuals at 3, 6, 9, and 12 months
      after disclosure.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7645598
TI  - Monosomy 9p24-->pter and trisomy 5q31-->qter: case report and review of two
      cases.
AB  - Partial deletion of the short arm of chromosome 9 (p24-->pter) and partial
      duplication of the long arm of chromosome 5 (q32-->qter) were observed in an
      abnormal boy who died at age 8 weeks of a complex cyanotic cardiac defect. He
      also had minor anomalies, sagittal craniosynostosis, triphalangeal thumbs,
      hypospadias, and a bifid scrotum. Two other infants with similar cytogenetic
      abnormalities were described previously. These patients had severe congenital
      heart defect, genitourinary anomalies, broad nasal bridge, low hairline,
      apparently low-set ears, short neck, and triphalangeal thumbs, in common with our
      patient. We suggest that combined monosomy 9p23,24-->pter and trisomy 5q31,32-
      >qter may constitute a clinically recognizable syndrome.

PMID- 7645599
TI  - Autosomal dominant inheritance in Setleis syndrome.
AB  - Setleis syndrome is characterized by bitemporal skin depressions resembling
      forceps marks, abnormalities of the eyelashes, and "leonine" facial appearance.
      The cause is unknown, although autosomal recessive inheritance has been proposed.
      Recently, two families were reported in which one of the parents of a patient
      with Setleis syndrome showed mild manifestations, suggesting autosomal dominant
      inheritance. We describe a 9-month-old Japanese boy with typical Setleis
      syndrome. His father, who has normal intelligence, has bitemporal focal dermal
      dysplasia but a normal face. His paternal second cousin also has Setleis
      syndrome. This family shows autosomal dominant inheritance including father-to
      son transmission of Setleis syndrome with variable expressivity and reduced
      penetrance. Careful examination of the relatives of patients with Setleis
      syndrome is recommended.

PMID- 7645600
TI  - Mixed sclerosing bone dysplasia, small stature, seizure disorder, and mental
      retardation: a syndrome?
AB  - We present a 40-year-old man with mental retardation, short stature, minor
      anomalies, and seizures, who was found to have osteopoikilosis with
      melorheostosis (mixed sclerosing bone dysplasia, MSBD). Cytogenetic findings of a
      low level trisomy 8 mosaicism were not confirmed by fluorescence in situ
      hybridization (FISH) of fibroblast cells. To our knowledge, the association of
      MSBD and mental retardation has not been previously reported.

PMID- 7645601
TI  - Supernumerary inv dup(15) in a patient with Angelman syndrome and a deletion of
      15q11-q13.
AB  - We have studied a patient with Angelman syndrome (AS) and a 47,XY,+inv dup(15)
      (pter-->q11::q11-->pter) karyotype. Molecular cytogenetic studies demonstrated
      that one of the apparently normal 15s was deleted at loci D15S9, GABRB3, and
      D15S12. There were no additional copies of these loci on the inv dup(15). The inv
      dup(15) contained only the pericentromeric sequence D15Z1. Quantitative DNA
      analysis confirmed these findings and documented a standard large deletion of
      sequences from 15q11-q13, as usually seen in patients with AS. DNA methylation
      testing at D15S63 showed a deletion of the maternally derived chromosome 15q11
      q13 on one of the apparently cytogenetically normal 15s, and not by the presence
      of an inv dup(15). This is the fourth patient with an inv dup(15) and AS or
      Prader Willi syndrome, who has been studied at the molecular level. In all cases
      an additional alteration of chromosome 15 was identified, which was hypothesized
      to be the cause of the disease. Patients with inv dup(15)s may be at increased
      risk for other chromosome abnormalities involving 15q11-q13.

PMID- 7645602
TI  - Craniosynostosis and kidney malformation in a case of Hennekam syndrome.
AB  - Hennekam syndrome is a rare autosomal recessive syndrome which was described for
      the first time in 1989. Here, we present a girl with intestinal lymphangiectasia,
      severe lymphedema of limbs, seizures, mild mental retardation, and facial
      anomalies consistent with the diagnosis of Hennekam syndrome. In addition, she
      had an ectopic kidney and craniosynostosis of the coronal suture, 2
      manifestations not previously reported in this syndrome. While the molecular
      basis of Hennekam syndrome remains, as yet, unknown, this report illustrates its
      variable clinical expression.

PMID- 7645603
TI  - Further contribution to the description of phenotypes associated with partial 4q
      duplication.
AB  - We report on a 15-year-old girl with a previously undescribed de novo duplication
      of segment 4q13.1-->q22.2. The origin of the extrachromosomal material on 4q was
      unequivocally established by fluorescent in situ hybridization with a chromosome
      4 painting probe. Clinical manifestations included moderate mental retardation,
      destructive behavior, and minor physical anomalies. An analysis of the literature
      on partial 4q trisomy led us to identify a region comprising bands 4q22-q23,
      which may be involved in the development of the acrorenal field.

PMID- 7645605
TI  - Parental origin of De Novo chromosome 9 deletions in del(9p) syndrome.
AB  - Parental origin of de novo deletions in the short arm of chromosome 9 in patients
      with a clinical diagnosis of del(9p) syndrome was assessed in 13 patients using
      polymerase chain reaction (PCR) analysis of highly polymorphic dinucleotide
      repeat microsatellite markers located in the putative deleted region. The
      deletion was found to be of paternal origin in 9 cases and of maternal origin in
      the remaining 4 cases, suggesting that the molecular event resulting in the
      deletion occurs in both male and female gametogenesis and that genomic imprinting
      does not appear to play a role in the pathogenesis of del(9p) syndrome.

PMID- 7645604
TI  - Neoplasms in Proteus syndrome.
AB  - We report on 2 children with Proteus syndrome who developed neoplasms. Patient 1
      had a probable mesothelioma, although papillary carcinoma of the thyroid could
      not be completely ruled out. Patient 2 had bilateral ovarian serous cystadenomas
      with nuclear atypia. Other unusual neoplasms in Proteus syndrome are discussed,
      together with their etiologic and pathogenetic possibilities.

PMID- 7645606
TI  - Hands and feet in the Apert syndrome.
AB  - We studied 44 pairs of hands and 37 pairs of feet in Apert syndrome, utilizing
      clinical, dermatoglyphic, and radiographic methods. We also studied histologic
      sections of the hand from a 31-week stillborn fetus. Topic headings discussed
      include: clinical classification of syndactyly; correlations between types of
      hands and feet in the same patient; dermatoglyphics; anatomy of the hand;
      radiologic assessment; comparison with other studies; histologic assessment of
      the hand; acrocephalosyndactyly vs. acrocephalopolysyndactyly: a
      pseudodistinction; and some generalizations.

PMID- 7645608
TI  - A piece of my mind.

PMID- 7645607
TI  - Diaphragmatic hernia in Denys-Drash syndrome.
AB  - We report on a newborn infant with male pseudohermaphroditism and glomerular
      lesions (Denys-Drash syndrome) but without Wilms tumor. A constitutional
      heterozygous mutation in the WT1 gene (366Arg to His) was identified. In addition
      the child had a large diaphragmatic hernia, so far not described in Denys-Drash
      syndrome. The expression of the WT1 gene in pleural and abdominal mesothelium and
      the occurrence of diaphragmatic hernia in transgenic mice with a homozygous WT1
      deletion strongly suggests that the diaphragmatic hernia in this patient is part
      of the malformation pattern caused by WT1 mutations.

PMID- 7645609
TI  - Predictive factors from cold knife conization for residual cervical
      intraepithelial neoplasia in subsequent hysterectomy.
AB  - OBJECTIVE: The optimal management of cervical intraepithelial neoplasia after
      cold knife conization remains controversial. Reliable predictors of residual
      dysplasia in the cervix after cold knife conization have not been consistently
      identified. This study was initiated to examine the accuracy of the traditional
      factors used to predict residual dysplasia in hysterectomy specimens after cold
      knife conization. STUDY DESIGN: A retrospective 10-year chart review identified a
      cohort of 1272 patients who underwent cold knife conization, of whom 311 had a
      subsequent hysterectomy within 1 year of conization. Residual disease was defined
      as cervical intraepithelial neoplasia or cancer in the hysterectomy specimen. All
      cone specimens were completely submitted for pathologic examination, and the
      following factors were analyzed for their predictive value: degree of dysplasia,
      margin involvement, endocervical gland involvement, and status of the
      endocervical curettage. The predictive value of age, race, gravidity, parity,
      socioeconomic status, cigarette smoking, and marital status were also examined.
      The chi 2 test, t test, and logistic regression were used for statistical
      analysis. RESULTS: Dysplasia or cancer were identified in 1066 (84%) of the 1272
      patients who underwent cold knife conization. Of the 311 patients having a
      subsequent hysterectomy, 106 (34%) had residual disease in their hysterectomy
      specimen. By multivariate analysis only increasing age and degree of dysplasia
      were predictive of residual disease. The odds ratio of residual disease in the
      hysterectomy specimen for a 25-year-old woman was 2.7 (95% confidence interval
      1.6 to 4.4) compared with a 40-year-old woman whose odds ratio was 4.9 (95%
      confidence interval 2.2 to 10.8). The presence of dysplasia in the cold knife
      conization specimen conferred an odds ratio of 12.1 (95% confidence interval 2.7
      to 54.5) of identifying residual disease. Dysplasia involving the ectocervical
      margin, endocervical margin, and endocervical glands was not predictive of
      disease in the hysterectomy specimens. Endocervical curettage was not performed
      in 44% of the patients, preventing reliable statistical evaluation. Further
      analysis indicated that residual disease was found in 32% of the hysterectomy
      specimens with negative margins, in 31% with no endocervical gland involvement,
      and in 23% with a negative endocervical curettage sample. CONCLUSIONS: The
      presence or absence of dysplasia in the cold knife conization ectocervical
      margin, endocervical margin, and endocervical glands was not predictive of
      residual dysplasia in post-cold knife conization hysterectomy specimens.
      Increasing age and severity of disease in the cone specimen were the only factors
      that accurately predicted residual dysplasia. The traditional factors used to
      justify hysterectomy after cold knife conization may not be valid on the basis of
      these results.

PMID- 7645610
TI  - Intrapartum hepatitis B screening.
AB  - OBJECTIVE: The purpose of this study was to determine the prevalence of acute
      hepatitis B in intrapartum patients and to describe the birth-to-administration
      interval of the hepatitis B vaccine and immune globulin in hepatitis B surface
      antigen-positive patients detected by intrapartum screening. STUDY DESIGN:
      Hepatitis B screening was performed on 8712 laboring patients admitted to Forsyth
      Memorial Hospital in Winston-Salem, North Carolina, between July 1, 1992, and
      Jan. 31, 1994. RESULTS: Fourteen laboring patients had positive results for
      hepatitis B surface antigen (prevalence 0.16%), and two of the 14 had a profile
      consistent with acute disease. The average interval from birth to administration
      of the hepatitis B immune globulin and hepatitis B virus vaccine was 18.6 hours
      (range 3.9 to 31.0 hours) for hepatitis B virus-infected patients whose hepatitis
      B surface antigen status was unknown before labor. CONCLUSION: Intrapartum
      screening allows for diagnosis of the asymptomatic patient with acute hepatitis B
      virus infection whose hepatitis B surface antigen status was unknown before labor
      who would not have received hepatitis B immune globulin had only early prenatal
      screening been performed.

PMID- 7645611
TI  - Fetal oxytocin and its extended forms at term with and without labor.
AB  - OBJECTIVE: We examined the concentrations of oxytocin and extended forms of
      oxytocin in umbilical plasma with and without labor. STUDY DESIGN: Umbilical
      venous and arterial blood were sampled in 27 term fetuses delivered vaginally and
      13 delivered abdominally before labor. Extended forms and oxytocin were measured
      by radioimmunoassay and compared by analysis of variance or t test. RESULTS:
      Concentrations of extended forms were higher than oxytocin concentrations (24.7
      +/- 3.1 vs 6.1 +/- 1.2 pg/ml, p < 0.01). Extended forms were higher in umbilical
      venous than in arterial plasma (29.6 +/- 5.0 vs 19.8 +/- 3.1 pg/ml, p < 0.05);
      oxytocin concentrations were not significantly different (4.7 +/- 1.6 vs 7.8 +/-
      1.8 pg/ml). Concentrations of extended forms were markedly lower with than
      without labor (17.1 +/- 3.0 vs 37.1 +/- 5.7 pg/ml, p = 0.01). Ratios of extended
      forms over oxytocin decreased with labor. CONCLUSION: In umbilical plasma
      extended forms of oxytocin are more abundant than oxytocin. Extended forms
      originate in the uterus and decrease markedly with labor.

PMID- 7645612
TI  - Methods of and attitudes toward screening obstetrics and gynecology patients for
      domestic violence.
AB  - OBJECTIVE: Our purpose was to define screening behaviors of obstetrician
      gynecologists and barriers to screening their patients for domestic violence.
      STUDY DESIGN: A questionnaire was developed to collect information on current
      practices and attitudes regarding screening for domestic violence. A randomly
      selected sample of obstetrician-gynecologists was surveyed. Respondents were also
      asked to rank a series of 19 potential barriers that may affect screening.
      RESULTS: Of 6568 physicians sampled, 962 (14.6%) returned questionnaires. Of the
      respondents, 77.6% were male and 22.4% were female. Male physicians were less
      likely to screen for domestic violence (25.9% vs. 18.9%). Thirty-four percent
      said that they had no training in abuse. Physicians indicating they had received
      training in abuse were more likely to screen for domestic violence. The lack of
      education was identified as the most common barrier physicians have to screening.
      The feeling that abuse was not a problem in their patients (46%), lack of time to
      deal with abuse (39.2%), and frustration that the physician cannot help the
      victim (34.2%) were other common barriers. CONCLUSION: The majority of
      obstetrician-gynecologists do not screen their patients for current or past
      domestic violence. If universal screening is to become a reality, educational
      tools and training materials are needed to overcome physician barriers.

PMID- 7645613
TI  - Route of delivery for the breech presentation: a conundrum.
AB  - OBJECTIVE: Our purpose was to determine the feasibility of resolving the
      controversy regarding route of delivery for breech presentation in a randomized,
      prospective fashion. STUDY DESIGN: The National Institute of Child Health and
      Human Development-sponsored Maternal-Fetal Medicine Units Network, which is
      composed of 11 perinatal centers, was surveyed to determine the feasibility of a
      randomized clinical trial of cesarean section versus trial of labor for breech
      presentation. A review of the literature was performed to determine the
      experience of other investigators with designing and conducting an adequate
      prospective, randomized trial. RESULTS: Principal investigators and faculty from
      seven of 11 centers within the Maternal-Fetal Medicine Units Network agreed to
      participate adn felt that they could adequately recruit patients for a trial in
      very-low-birth-weight infants. This would provide approximately 200 very-low
      birth-weight fetuses in a breech presentation per year. Sample size calculations
      indicated that 1700 infants would be required. Investigators also had strong
      reservations about performing a trial of vaginal breech delivery for other
      gestational ages. A review of the literature indicates that other authors have
      encountered difficulty in attempting randomized clinical trials of this nature.
      CONCLUSIONS: The Maternal-Fetal Medicine Units Network with its pool of 60,000
      deliveries per year agreed that a randomized, controlled delivery route of labor
      in the 24- to 28-week breech presentation was not feasible in a reasonable period
      of time. A randomized clinical trial of larger fetuses in a breech presentation
      was also considered extremely difficult. These findings are similar to those of
      other authors who have attempted or proposed randomized clinical trials to
      determine the safety of planned vaginal delivery of the breech presentation at
      various gestational ages.

PMID- 7645614
TI  - Radical hysterectomy: does the type of incision matter?
AB  - OBJECTIVE: Our purpose was to evaluate and compare aspects of operative
      accessibility and perioperative outcome after radical hysterectomy and pelvic
      lymphadenectomy performed through a vertical, Pfannenstiel, or Maylard abdominal
      incision. STUDY DESIGN: During an 8-year interval, 236 patients underwent radical
      hysterectomy and pelvic lymphadenectomy as primary treatment for cervical cancer
      at the Watson Clinic. Patients were admitted under a standard perioperative
      protocol, and all procedures were performed by a gynecologic oncologist. All
      clinical data was recorded prospectively and updated regularly. RESULTS: Radical
      hysterectomy and pelvic lymphadenectomy was completed through a vertical (n =
      113), Pfannenstiel (n = 78), or Maylard (n = 45) incision. Although lesion size
      and depth of stromal invasion was not different between incision types, patients
      with a Pfannenstiel incision were younger (p < 0.001) and weighed less than those
      with a vertical (p = 0.001) or Maylard (p < 0.025) incision. The Pfannenstiel was
      associated with a shorter operative time (Pfannenstiel vs Maylard, p < 0.05;
      Pfannenstiel vs vertical, p < 0.001), less blood loss (Pfannenstiel vs Maylard, p
      < 0.025; Pfannenstiel vs vertical, p < 0.001), a lower risk of transfusion, and a
      shorter hospital stay (Pfannenstiel vs Maylard, p < 0.025; Pfannenstiel vs
      vertical, p < 0.001). These differences persisted when controlled for patient
      weight and surgical experience. There was no significant difference in the total
      number of nodes evaluated. No patient had a positive vaginal margin. CONCLUSION:
      Radical hysterectomy and pelvic lymphadenectomy can be safely performed through a
      vertical, Maylard, or Pfannenstiel incision. In a selected population a
      Pfannenstiel incision offers the potential benefit of less abdominal wall trauma
      without compromising surgical exposure or increasing the risk of surgical
      complications.

PMID- 7645615
TI  - Correlation of urodynamic measures of urethral resistance with clinical measures
      of incontinence severity in women with pure genuine stress incontinence. The
      Continence Program for Women Research Group.
AB  - OBJECTIVE: Our aim was to correlate multiple measures of urethral resistance with
      five clinical measures of incontinence severity in women with pure genuine stress
      incontinence. STUDY DESIGN: Seventy-five women with pure genuine stress
      incontinence underwent passive and dynamic urethral pressure profilometry and
      Valsalva leak point pressure determinations. The standardized and validated
      measures of incontinence severity included (1) the number of incontinent
      episodes, (2) the number of continence pads used recorded in a prospective 1-week
      urinary dairy, (3) grams of fluid loss on a pad quantitation test, and (4) two
      condition-specific quality-of-life scales, the urogenital distress inventory and
      the incontinence impact questionnaire. The urodynamic and severity measures were
      compared with Pearson product-moment correlation analysis. RESULTS: There were no
      significant correlations between dynamic urethral pressure profile pressure
      transmission ratios and any measure of incontinence severity. Passive urethral
      pressure profile variables correlated significantly with incontinence episodes
      and pad use. Valsalva leak point pressures correlated significantly with pad use
      and quantitation testing. None of the urodynamic measurements was significantly
      correlated with either of the quality-of-life scales, but our power to
      demonstrate a correlation was limited. CONCLUSIONS: Both passive urethral
      pressure profile measures and Valsalva leak point pressures correlate with some
      severity measures of genuine stress incontinence. Although inefficient pressure
      transmission during stress is critical to the pathogenesis of genuine stress
      incontinence, the severity of the pressure transmission defect is not related to
      clinical severity. Conversely, impairment of intrinsic urethral resistance is not
      essential to the pathogenesis of genuine stress incontinence, but the degree of
      sphincteric impairment is related to severity once the condition exists.

PMID- 7645616
TI  - Endometrial cancer: stage at diagnosis and associated factors in black and white
      patients.
AB  - OBJECTIVE: This study examined the relationship of clinicopathologic, health
      status, medical system, and socioeconomic factors to differences in stage at
      diagnosis of endometrial cancer in black and white patients. STUDY DESIGN: A
      population-based study of 130 black and 329 white patients with invasive
      endometrial cancer was conducted as part of the National Cancer Institute's
      Black/White Cancer Survival Study. Logistic regression was used to determine the
      relative importance of factors thought to be related to stage at diagnosis after
      age and geographic location were adjusted for. RESULTS: High-grade (poorly
      differentiated) lesions increased the risk for stage III or IV disease (odds
      ratio 8.3, 95% confidence interval 3.4 to 20.3), as did serous histologic subtype
      (odds ratio 3.5, 95% confidence interval 1.4 to 8.8) and no usual source of care
      (odds ratio 5.5, 95% confidence interval 1.4 to 20.9). In the final statistical
      model these three factors also accounted for the majority of the excess risk of
      advanced stage for blacks. CONCLUSIONS: Black-white racial disparities in stage
      at diagnosis appear to be related to higher-grade lesions and more aggressive
      histologic subtypes occurring more frequently in black patients with endometrial
      cancer.

PMID- 7645617
TI  - Cytologic screening after hysterectomy for benign disease.
AB  - OBJECTIVE: Our purpose was to determine the effectiveness of vaginal cytology
      tests after hysterectomy for benign disease. STUDY DESIGN: We studied a 10-year
      retrospective cohort of patients after hysterectomy (n = 697 women, 9074 woman
      years). Patients were excluded if they had any type of invasive gynecologic
      malignancy. The main outcome variable was development of a vaginal cytologic
      abnormality, evaluated with Kaplan-Meier estimates and proportional hazards
      regression. RESULTS: We found 33 abnormal cytology results; most were of little
      clinical significance except for two biopsy-proven dysplasia cases. When we
      controlled for age, the risk was 4.67 for patients with a history of a cervical
      cytologic abnormality (95% confidence interval 2.1 to 10.6). We needed 633 tests
      to detect one true positive case of vaginal dysplasia. CONCLUSIONS: The low
      incidence of vaginal dysplasia and carcinoma, combined with the high false
      positive rate, supports decreasing the number of screening tests performed for
      these low-risk patients.

PMID- 7645618
TI  - Cohort study of twinning in an academic health center: changes in management and
      outcome over forty years.
AB  - OBJECTIVE: Our purpose was to explore the management and outcomes of twin
      pregnancies over 40 years (1952 to 1993) within a single academic health center.
      STUDY DESIGN: According to a retrospective cohort design, twin pregnancies were
      collected and the following variables were analyzed: maternal age, parity,
      gestational age, birth weight, twin gender, presentation, delivery route,
      intervals between births, Apgar scores, and perinatal outcome. Information was
      broken into approximately decade-long epochs (1952 to 1962, 1963 to 1972, 1973 to
      1982, 1983 to 1993) to compare trends over time. RESULTS: A total of 814 twin
      pregnancies were delivered. Median birth weight and gestational age decreased
      over time. The prevalence of > 20% birth weight discordancy was 23% and did not
      increase. Nulliparity increased over time but maternal age did not. Same-sex
      pairs were constant, as was presentation. Use of abdominal delivery and the
      abdominal delivery of a nonvertex second twin after vaginal delivery of the first
      increased in the last two epochs. Both the interval between births and the Apgar
      score of the second twin increased over time. Perinatal mortality of very-low
      birth-weight and normal-birth-weight twins decreased over time. CONCLUSIONS: The
      maternal demographics of twinning changed little over 40 years. Gestational age
      and birth weight decreased over time because of the regionalization of perinatal
      care. Birth weight-specific perinatal mortality improved over time.

PMID- 7645619
TI  - Sacrospinous suspension: a local practitioner's experience.
AB  - OBJECTIVE: The objective of the study was to determine the effectiveness of
      transvaginal sacrospinous fixation of the vaginal vault as part of the total
      pelvic reconstructive surgery performed for patients with uterovaginal prolapse
      and vaginal vault prolapse. STUDY DESIGN: The hospital and office records of 156
      patients undergoing sacrospinous suspension of the vaginal vault between Sept.
      14, 1987, and March 22, 1994, were retrospectively reviewed. The preoperative
      pelvic support defects were compared with the postoperative pelvic support
      defects. The proportion test for independent samples was used to determine
      statistical significance. RESULTS: Eight (5.6%) patients have had recurrence of
      vaginal vault prolapse, with two of these patients having undergone repeat pelvic
      reconstructive surgery. Eleven (7.6%) patients have had recurrent anterior
      segment defects, whereas two (1.4%) patients have had recurrent posterior segment
      defects. CONCLUSION: Ninety-four percent of the patients who underwent
      sacrospinous suspension for uterovaginal prolapse and vaginal vault prolapse have
      had no persistence or recurrence of vaginal vault prolapse 6 to 83 months after
      the procedure.

PMID- 7645620
TI  - Interleukin-1 beta and interleukin-4 increase parathyroid hormone-related protein
      secretion by human umbilical vein endothelial cells in culture.
AB  - OBJECTIVE: Our purpose was to learn whether cytokines such as interleukin-1 beta
      and related (or antagonistic) cytokines, hormones, and growth factors could
      regulate secretion of the vasorelaxant parathyroid hormone-related protein in
      human umbilical vein endothelial cells in culture. STUDY DESIGN: Secondary
      cultures of human umbilical vein endothelial cells were grown to confluence and
      treated with interleukin-1 beta, an array of factors with possible regulatory
      actions (cytokines, growth factors, vasoactive peptides, and steroids), and a
      phorbol ester as a stimulatory control. After 24 hours immunoreactive parathyroid
      hormone-related peptide in the media was measured by a two-site sandwich
      radioimmunoassay. The mechanism of interleukin-1 beta action was probed with
      interleukin-1 beta receptor antagonist and selected inhibitors. RESULTS:
      Interleukin-1 beta (10 ng/ml) produced up to an eightfold increase in parathyroid
      hormone-related peptide secretion from human umbilical vein endothelial cells in
      culture (p < 0.01). Half-maximal stimulation was seen at 0.23 ng/ml. Interleukin
      1 receptor antagonist, cycloheximide, and actinomycin D blocked the effects of
      interleukin-1 beta (p < 0.05). Interleukin-4 at 10 ng/ml and phorbol 12-myristate
      13-acetate at 10(-7) mol/L significantly increased the secretion of parathyroid
      hormone-related peptide by human umbilical vein endothelial cells (p < 0.05). The
      time course of each interleukin showed an effect beyond 12 hours. The effects of
      interleukin-1 beta and interleukin-4 appeared to be specific, because a large
      series of related interleukins and other growth factors and cytokines were
      without effect. CONCLUSION: Interleukin-1 beta and interleukin-4 increase
      parathyroid hormone-related protein secretion in human umbilical vein endothelial
      cells in culture. Because interleukin-1 beta messenger ribonucleic acid has been
      found in umbilical cord endothelial cells, we propose that the umbilical cord has
      a novel vasorelaxant regulatory system that uses interleukin-1 beta endothelial
      action and secretion of the vasorelaxant parathyroid hormone-related peptide.

PMID- 7645621
TI  - Cytologic diagnosis of ovarian tumors: factors influencing accuracy in previously
      undiagnosed cases.
AB  - OBJECTIVES: Cytologic diagnosis of ovarian masses by needle aspiration techniques
      remains controversial. This review proposes to define the accuracy of the
      technique, report complications, and relate clinical situations in which the
      technique was used. STUDY DESIGN: In a retrospective review all patients
      undergoing cytologic aspiration biopsy diagnosis of ovarian masses at the
      University of Virginia Health Sciences Center from 1986 through 1993 were
      identified, and 74 women with corresponding histologic material were used.
      Clinical data were abstracted and all cytologic and pathologic material was
      reviewed. RESULTS: The overall sensitivity of the 74 aspiration biopsies to
      predict the histologic diagnosis of malignancy was 78%; specificity was 92%. Two
      patients had complications, one necessitating operative intervention. Correct
      diagnoses were influenced by menopausal status, patient age, sample type,
      aspiration method, and cytologic quality. CONCLUSIONS: The cytologic diagnoses of
      ovarian tumors, while quite specific, lack the sensitivity for general
      application. Use of this diagnostic technique must remain individualized, and the
      factors that influence the accuracy of the technique must be kept in mind. There
      remains the need for standardization of reporting fine needle aspiration results.

PMID- 7645622
TI  - Wound infection after abdominal hysterectomy: effect of the depth of subcutaneous
      tissue.
AB  - OBJECTIVE: Our purpose was to determine the effect of the depth of the
      subcutaneous tissue at the operative site on abdominal wound infection after
      hysterectomy. STUDY DESIGN: A prospective study was performed of women undergoing
      abdominal hysterectomy and not receiving antibiotic prophylaxis who underwent
      maximum vertical measurement of their subcutaneous incisions before the abdominal
      cavity was surgically entered. Additional demographic and perioperative data
      previously associated with wound infection were collected and analyzed. Surgical
      technique was standardized among the three attending surgeons involved. RESULTS:
      Wound infection occurred in 17 of 150 (11.3%) women undergoing abdominal
      hysterectomy. Univariate analysis identified the following risk factors as being
      significantly associated with wound infection: depth of subcutaneous tissue (p =
      0.0004), preoperative serum albumin (0.0015), weight (p = 0.0029), and body mass
      index (p = 0.0032). Logistic regression analysis confirmed the thickness of the
      subcutaneous tissue as the only significant risk factor for wound infection (p =
      0.04) (odds ratio 1.37, 95% confidence interval 1.01 to 1.86). No patients with a
      maximum depth of subcutaneous tissue < 3 cm had a wound infection. CONCLUSION: We
      conclude that the depth of subcutaneous tissue is the most significant risk
      factor associated with abdominal wound infection after hysterectomy.

PMID- 7645623
TI  - Initial and steady-state pharmacokinetics of a vaginally administered formulation
      of progesterone.
AB  - OBJECTIVE: The pharmacokinetics of a 100 mg vaginal progesterone suppository was
      evaluated on days 1 and 7 and a 200 mg suppository on day 14. All the volunteers
      were given oral 17 beta-estradiol during the study. STUDY DESIGN: Ten
      postmenopausal women volunteered for this study. Progesterone was given as a
      vaginal suppository. Peripheral venous samples were obtained at appropriate
      intervals and analyzed for 17 beta-estradiol and progesterone levels. Area under
      the curve for progesterone was assessed by the trapezoidal method. Statistical
      analysis was performed by a one-way analysis of variance. RESULTS: Serum 17 beta
      estradiol levels ranged from 22 to 182 pg/ml. Maximal serum progesterone levels
      ranged from 5.7 to 20.9 ng/ml, with the mean maximal levels 13.97, 16.09, and
      12.68 ng/ml (not significantly different) and a mean area under the curve of
      168.13, 207.64 and 227.71 ng/ml per hour on days 1, 7, and 14 (not statistically
      different). CONCLUSIONS: These data indicate that vaginal absorption of
      progesterone is efficient. The lack of difference in the area under the curve for
      both doses suggests that the vaginal mucosa or the total surface area of the
      vagina may limit the absorption of progesterone from the vagina.

PMID- 7645624
TI  - Maternal thrombocytopenia in pregnancy: time for a reassessment.
AB  - Antiplatelet autoantibodies in women with autoimmune thrombocytopenic purpura can
      cause fetal thrombocytopenia and serious bleeding problems. Obstetricians have
      used fetal scalp sampling, cordocentesis, and cesarean delivery in this disorder
      to avoid fetal complications such as intracranial hemorrhage. Accumulating
      evidence indicates that the fetal risk of intracranial hemorrhage is much lower
      than initially reported. Moreover, these invasive tests and treatments are
      costly, cause morbidity, and have little effect in preventing neonatal bleeding
      complications. Therefore we suggest these interventions should no longer be used
      in the management of maternal thrombocytopenia.

PMID- 7645625
TI  - Postnatal transmission of human immunodeficiency virus type 1: the breast-feeding
      dilemma.
AB  - Human milk has been considered only recently as a source of transmission for the
      human immunodeficiency virus. The estimated postnatal transmission rate from
      mothers who acquired human immunodeficiency virus infection while lactating is
      26% (95% confidence interval 13% to 39%) and may be in the range of 8% to 18%
      from mothers who were infected before becoming pregnant. Risk factors for
      postnatal transmission include maternal immune deficiency and the presence of
      human immunodeficiency virus-infected cells in milk. Some milk factors may be
      protective against postnatal transmission such as specific immunoglobulin A and
      immunoglobulin M and a molecule able to inhibit the binding of human
      immunodeficiency virus to CD4. In addition to its safety and its birth-spacing
      properties, breast-feeding provides immunologic protection and an ideal
      nutritional content to the infant. In a poor hygienic environment artificial
      feeding dramatically increases morbidity and mortality from diarrheal diseases
      and respiratory infections. Consequently, according to our current knowledge the
      World Health Organization and the United Nations Children's Fund reasonably
      recommend continuing breast-feeding promotion in women living in settings where
      infectious diseases and malnutrition are the primary causes of infant deaths such
      as in many developing countries. In settings where infectious diseases and
      malnutrition are not the primary causes of infant deaths, such as in most of the
      settings in the developed world, the advisory group recommends against breast
      feeding for mothers with proved human immunodeficiency virus-1 infection.

PMID- 7645626
TI  - Common dermatoses.
AB  - Skin diseases are an essential part of primary care medicine. Most dermatologic
      care is delivered in an outpatient setting. The initial evaluation is usually
      performed by the primary care physician. Women account for nearly 60% of all
      visits for dermatologic complaints.

PMID- 7645627
TI  - Uterine artery blood flow response to correction of amniotic fluid volume.
AB  - OBJECTIVE: Our purpose was to investigate whether acute alterations of amniotic
      fluid volume affect uteroplacental perfusion. STUDY DESIGN: Three groups of
      patients of comparable gestational age were studied in a fetal medicine referral
      unit: (1) eight pregnancies with severe polyhydramnios because of twin-twin
      transfusion syndrome undergoing therapeutic amnioreduction, (2) seven with severe
      oligohydramnios undergoing diagnostic amnioinfusion, and (3) six control women
      having invasive procedures of similar duration without manipulation of amniotic
      fluid volume. Color Doppler imaging was used to measure uterine artery impedance
      index values and quantitative blood flow before and within 15 minutes of the end
      of the procedure. RESULTS: Quantitative flow measurements increased after
      amnioreduction (74% median increase of volume flow, range 22% to 329%, p < 0.01)
      and decreased after amnioinfusion (33% median decrease of volume flow, range 17%
      to 51%, p < 0.05). Impedance index values increased after amnioinfusion (25%
      median increase in pulsatility index, range 4% to 71%, p < 0.05) and did not
      alter with amnioreduction. There were no significant changes in the control
      group. CONCLUSION: Acute changes in amniotic fluid volume alter uteroplacental
      perfusion. In twin-twin transfusion syndrome amelioration in uterine flow may
      improve fetal condition and explain in part the success of serial amnioreduction
      therapy.

PMID- 7645628
TI  - Hyperechogenic fetal bowel: an ultrasonographic marker for adverse fetal and
      neonatal outcome.
AB  - OBJECTIVE: Fetal hyperchogenic bowel is associated with a variety of conditions,
      the incidence of which has yet to be studied. STUDY DESIGN: The outcomes of 182
      cases of fetal hyperechogenic bowel were reviewed. Screening for maternal
      toxoplasmosis, fetal karyotyping, and amniotic fluid digestive enzyme assays were
      performed in all cases. Eight mutations associated with cystic fibrosis were
      analyzed in 116 cases. RESULTS: Of 135 newborns, 121 were normal, but nine
      underwent surgery for gastrointestinal obstruction, three had cytomegalovirus or
      parvovirus infection, one had a triple X chromosome, and one died from sudden
      infant death syndrome. In utero fetal death was observed in 24 cases. Elective
      termination of pregnancy was performed in 23 cases for associated anomalies.
      CONCLUSIONS: Hyperechogenic fetal bowel was associated with increased risk for
      adverse outcome. Prenatal management should include ultrasonographic
      surveillance, fetal karyotyping, amniotic digestive enzyme assays, and screening
      for cystic fibrosis and infectious disease.

PMID- 7645629
TI  - Effects of prenatal ethanol exposure on the hippocampal neurochemistry of albino
      rats at 90 days of postnatal age.
AB  - OBJECTIVE: Our purpose was to test the hypothesis that prenatal ethanol exposure
      alters the hippocampal muscarinic cholinergic neurochemistry of albino rats.
      STUDY DESIGN: Ethanol was administered in a liquid diet to pregnant albino
      Sprague-Dawley rats. Liquid diet control animals received the same diet in which
      ethanol was replaced by an isocaloric amount of maltose-dextrin. Chow-fed control
      animals were fed laboratory chow as desired. Progeny were killed at 90 days of
      age, and their hippocampi were analyzed for muscarinic cholinergic receptors by
      use of tritiated quinuclidinyl benzilate. RESULTS: Prenatal ethanol exposure
      produced a statistically significant decrease in the number of muscarinic
      receptors in males. Similar trends were noted in females, but the results were
      not statistically significant. CONCLUSION: Prenatal ethanol treatment caused long
      lasting alterations in the muscarinic cholinergic receptors of the hippocampus in
      male rats.

PMID- 7645630
TI  - Is oligohydramnios in postterm pregnancy associated with redistribution of fetal
      blood flow?
AB  - OBJECTIVE: Our purpose was to determine whether postterm patients with
      oligohydramnios differ in their fetal and umbilical blood flow distribution from
      those with a normal volume of amniotic fluid. STUDY DESIGN: Pulsed-wave Doppler
      imaging was used prospectively to determine the resistance index in the fetal
      middle cerebral, renal, and umbilical arteries in 57 postterm (i.e., > 41 weeks'
      gestation) pregnancies. Semiquantitative assessment of amniotic fluid volume was
      obtained by use of the ultrasonographically determined amniotic fluid index.
      RESULTS: Oligohydramnios (amniotic fluid index < 5 cm) was detected in 15
      patients; 42 patients with a normal amniotic fluid index served as a control
      group. The various resistance index values and the ratio s among them were not
      significantly different when patients with oligohydramnios were compared with
      controls (0.51 +/- 0.1 vs 0.52 +/- 0.06, 0.63 +/- 0.1 vs 0.64 +/- 0.08, and 0.71
      +/- 0.08 vs 0.73 +/- 0.05 for the umbilical, middle cerebral, and renal arteries,
      respectively). However, the mean birth weight (in grams) was significantly lower
      (3297 +/- 438 vs 3742 +/- 448, p < 0.003), in the oligohydramnios group.
      CONCLUSION: Oligohydramnios was not associated with a major redistribution of
      blood flow in postterm patients, suggesting that the cause of oligohydramnios in
      these patients is related to birth weight rather than to renal perfusion.

PMID- 7645631
TI  - Distance from an intrauterine hydrophone as a factor affecting intrauterine sound
      pressure levels produced by the vibroacoustic stimulation test.
AB  - OBJECTIVE: The purpose of this study was to determine whether intrauterine sound
      pressure levels produced by vibroacoustic stimulation were associated with
      distance from an intrauterine hydrophone in human parturients and to evaluate the
      effects of distance on the spectrum of the stimulus. STUDY DESIGN: Measurements
      of intrauterine sound were taken in eight volunteer parturients in normal active
      phase labor by use of an intrauterine hydrophone. Vibroacoustic stimulation was
      performed on the maternal abdomen directly overlying the hydrophone; at distance
      of 5, 10, 15, 20, and 25 cm from the hydrophone; and at the maternal sternum.
      Intrauterine sound pressure levels were tape-recorded for later analysis. Fetal
      heart rate and fetal movement were assessed with each vibroacoustic stimulation.
      Spectral analyses were performed by taking the fast Fourier transform of the tape
      recorded stimulation at each position. RESULTS: Analysis of variance with
      repeated measures indicated a statistically significant decrease (F = 4.1, p =
      0.004) in the sound pressure levels as distance increased. Spectral analysis
      indicated large variability between and within subjects. CONCLUSION: Sound
      exposure of the fetal ear is on average decreased as the distance between the ear
      and the vibroacoustic stimulation is increased. The spectrum of the stimulus
      produced with vibroacoustic stimulation is highly variable.

PMID- 7645632
TI  - Determinants of cervical ectopia and of cervicitis: age, oral contraception,
      specific cervical infection, smoking, and douching.
AB  - OBJECTIVE: Our purpose was to assess determinants of cervical ectopia and
      cervicitis, specifically after adjustment for cervical infection. STUDY DESIGN: A
      cross-sectional study was conducted with colposcopic, cytologic, and
      microbiologic examination of 764 randomly selected women attending a sexually
      transmitted disease clinic and 819 consecutive college students undergoing
      routine annual examination. RESULTS: After we controlled for potential
      confounders, cervical ectopia was positively associated with oral contraception
      and Chlamydia trachomatis infection and negatively associated with aging in both
      populations, with recent vaginal douching in patients with sexually transmitted
      diseases, and with current smoking in college students. Oral contraception wa
      also associated with the radius of ectopia, and among users of oral contraception
      ectopia was associated with duration of oral contraception. Cervicitis (evaluated
      by Gram stain, Papanicoloau smear, and colposcopy) was associated with cervical
      infection by C. trachomatis and cytomegalovirus (both populations) and with
      gonorrhea and cervical herpes simplex virus infection (patients with sexually
      transmitted diseases). Cervicitis was independently associated with ectopia but
      not with oral contraception after we adjusted for these four cervical infections.
      However, oral contraception was associated with edema and erythema of the zone of
      ectopia among women without cervical infection. CONCLUSIONS: Oral contraception,
      aging, cervical infection, smoking, and douching have effects on cervical ectopia
      that may influence the acquisition, transmission, or effects of sexually
      transmitted agents. Ectopia is associated with young age, oral contraception, and
      cervical infection; cervicitis is associated with ectopia and cervical infection
      by C. trachomatis, Neisseria gonorrhoeae, herpes simplex virus, and
      cytomegalovirus. In women without cervical infection, edema and erythema of the
      zone of ectopia are associated with oral contraception.

PMID- 7645633
TI  - Prior and current health characteristics of postmenopausal estrogen replacement
      therapy users compared with nonusers.
AB  - OBJECTIVE: Our purpose was to investigate whether selection of healthy women for
      postmenopausal estrogen therapy may confound observational studies of estrogen
      use and cardiovascular disease risk. STUDY DESIGN: Data were obtained from
      baseline (1981 to 1984) and follow-up (1990 to 1992) health surveys of two
      cohorts randomly selected from communities in southeastern New England. At follow
      up postmenopausal women > or = 40 years old were categorized as current users (n
      = 70) or nonusers (n = 772) of noncontraceptive estrogen. Users and nonusers were
      compared on both prior characteristics from the baseline surveys and current
      characteristics measured at follow-up by use of analysis of covariance. RESULTS:
      Prior levels of total and high-density lipoprotein cholesterol, body mass index,
      and blood pressure were similar for estrogen users and nonusers. Estrogen users
      were less likely to have smoked and more likely to have had their cholesterol
      checked and to exercise regularly. These differences were more pronounced for
      current characteristics than for baseline characteristics. CONCLUSIONS: Selection
      of healthy women for treatment may not fully explain the apparent protective
      effect of estrogen replacement on cardiovascular risk. However, more healthy
      profiles among estrogen users may inflate the apparent benefit of treatment in
      observational studies.

PMID- 7645634
TI  - Valsalva leak point pressures in women with genuine stress incontinence:
      reproducibility, effect of catheter caliber, and correlations with other measures
      of urethral resistance. Continence Program for Women Research Group.
AB  - OBJECTIVES: The Valsalva leak point pressure has been promoted as an alternative
      to urethral pressure profilometry as a measure of urethral resistance in women
      with genuine stress incontinence. Our aims were to evaluate the reproducibility
      of the Valsalva leak point pressure, to assess the effect of catheter caliber on
      the Valsalva leak point pressure, and to compare vesical Valsalva leak point
      pressure to other measures of urethral resistance. STUDY DESIGN: Sixty
      consecutive women with genuine stress incontinence underwent duplicate Valsalva
      leak point pressure determinations by use of 8F and 3F vesical and 8F vaginal
      catheters. Subjects also underwent a standard resting urethral pressure
      profilometry, cough leak point pressure determinations, and pressure-flow
      micturition studies. RESULTS: Leakage was demonstrated on both Valsalva maneuvers
      in approximately 80% of subjects with both catheters. In subjects who leaked with
      both strains there was an extremely high correlation between the test-retest
      Valsalva leak point pressure within both catheters. The intercatheter correlation
      between the 8F and 3F Valsalva leak point pressures was significant but much
      weaker than the intracatheter correlations; 8F Valsalva leak point pressures were
      significantly higher than 3F Valsalva leak point pressures, although there were
      individual exceptions to this observation. Urethral pressure profilometry
      measures and micturition opening pressures were poorly correlated with Valsalva
      leak point pressure. Cough and vaginal Valsalva leak point pressures were
      significantly correlated with vesical Valsalva leak point pressure, but cough
      leak point pressures were significantly higher and vaginal Valsalva leak point
      pressures were significantly lower than the vesical Valsalva leak point pressure.
      CONCLUSIONS: Valsalva leak point pressure is a simple and reproducible technique
      for evaluating urethral resistance in women with genuine stress incontinence.
      However, variations in Valsalva leak point pressure measurement must be precisely
      described, standardized, and validated before a technique can be advocated for
      clinical use.

PMID- 7645635
TI  - Expression of two mucin antigens in cultured human ovarian surface epithelium:
      influence of a family history of ovarian cancer.
AB  - OBJECTIVE: The genetic changes in hereditary ovarian cancer syndromes suggest
      that the phenotype of ovarian surface epithelium in women with familial ovarian
      cancer might be altered. To test this hypothesis, we compared two tumor markers,
      CA 125 and 2G3, in cultures of overtly normal epithelium from patients with and
      without familial ovarian cancer. STUDY DESIGN: Surface epithelia from 18 patients
      with no family history of ovarian cancer, five with family histories that were
      insufficient to be classified as familial, and seven with strong family histories
      were examined by immunofluorescence, immunocytochemistry, and radioimmunoassay.
      The influence of cell density, morphologic features, propagation in culture, and
      immortalization with SV40 on the expression of the markers was investigated.
      RESULTS: CA 125 occurred in cells with epithelial rather than atypical
      morphologic features. In cultures with no family history and minor family
      history, CA 125 was present in up to 45% cells in passage 1 but in only < 5%
      cells in 14 of 16 cultures by passages 3 to 4. In contrast, nine of 10 cultures
      with family history retained > 5% CA 125-positive cells in passages 3 to 4. This
      prolonged presence of CA 125 correlated with a persisting epithelial phenotype,
      whereas most cells with no family history and minor family history became
      atypical by passage 3. Immortalization eliminated CA 125 in all three types of
      cells. 2G3 bound to few cells in low passage, independent of family history and
      morphologic features. The proportion of 2G3-expressing cells increased
      significantly with immortalization in all cultures, independent of family
      history. Ovarian carcinoma lines expressed both markers. CONCLUSION: In cultures
      of ovarian surface epithelium 2G3 expression increases with immortalization,
      whereas CA 125 is lost with immortalization but correlates with epithelial cell
      morphologic features and with family history. The results suggest that there may
      be phenotypic changes in overtly normal ovarian surface epithelium of women with
      family histories of ovarian cancer.

PMID- 7645636
TI  - Mitogenic effect of basic fibroblast growth factor and estradiol on cultured
      human myometrial and leiomyoma cells.
AB  - OBJECTIVE: We compared the mitogenic effect of basic fibroblast growth factor
      with and without estradiol on myometrial and leiomyometrial cells. STUDY DESIGN:
      The mitogenic effect of basic fibroblast growth factor on myometrial cells was
      measured by thymidine incorporation and cell count. The mitogenic effect of basic
      fibroblast growth factor with and without estradiol as measured by thymidine
      incorporation was compared between myometrial and leiomyometrial cells. RESULTS:
      Both human myometrial and leiomyometrial cells showed significant (p = 0.004 and
      p = 0.001, respectively), dose-dependent incorporation of thymidine in response
      to basic fibroblast growth factor. Leiomyometrial cells showed significantly (p =
      0.04) less thymidine incorporation compared with matched normal myometrial cells.
      The addition of estradiol with basic fibroblast growth factor did not result in a
      further increase in thymidine incorporation. CONCLUSIONS: Both myometrial and
      leiomyometrial cells respond to basic fibroblast growth factor with increased
      thymidine incorporation; however leiomyometrial cells are less responsive than
      are matched normal myometrial cells. The addition of estradiol is not synergistic
      with basic fibroblast growth factor.

PMID- 7645637
TI  - Maternal serum thromboxane B2 reduction versus pregnancy outcome in a low-dose
      aspirin trial.
AB  - OBJECTIVE: Our purpose was to determine whether in a low-dose aspirin trial a
      longitudinal decrease in maternal serum thromboxane B2 is associated with
      improvement in pregnancy outcomes. STUDY DESIGN: A total of 606 healthy
      nulliparous women with singleton gestations were randomized at 24 weeks to either
      60 mg of aspirin or a placebo. Maternal serum thromboxane B2 was measured at
      randomization, at 29 to 31 weeks, at 34 to 36 weeks, and at delivery. After
      delivery, and without knowledge of patient outcome or group assignment, patients
      were categorized as having had either a longitudinal twofold or greater (> or =
      50%) or less than twofold reduction (< 50%) in thromboxane B2 from baseline
      levels at randomization. RESULTS: Of 606 entrants, 92% had sufficient thromboxane
      B2 determinations to allow categorization. Whether patients were assigned to
      aspirin or placebo, birth weight was significantly greater in women who had a
      twofold or greater reduction in maternal serum thromboxane B2 levels. When the
      aspirin and placebo groups were combined, women with a twofold or greater
      reduction in thromboxane B2 levels had less preeclampsia, 1.9% (6/314) versus
      5.7% (14/244) (p = 0.016), less preterm delivery (5.7% vs 10.7%, p = 0.032),
      fewer small-for-gestational-age newborns, 9 of 314 (2.95) versus 17 of 244 (7%)
      (p = 0.023), and a higher mean birth weight, 3314 gm versus 3121 gm (p = 0.0001).
      CONCLUSION: Women with a twofold or greater longitudinal reduction in maternal
      serum thromboxane B2 had less preeclampsia and prematurity, fewer small-for
      gestational-age newborns, and higher birth weights than women with less than a
      twofold reduction.

PMID- 7645638
TI  - The relationship of the duration of ruptured membranes to vertical transmission
      of human immunodeficiency virus.
AB  - OBJECTIVE: Intrapartum events may play a role in determining the likelihood of
      vertical transmission of human immunodeficiency virus-1. Timing and duration of
      rupture of membranes have been shown to modify transmission risk of other
      organisms but have not been examined for human immunodeficiency virus. This study
      was undertaken to assess the relationship between duration of rupture of
      membranes, maternal immune status, and transmission of human immunodeficiency
      virus. METHODS: The Mothers' and Infants' Cohort Study enrolled 207 human
      immunodeficiency virus-positive women and their infants at five study sites in
      Brooklyn and the Bronx, New York between January 1986 and January 1991. One
      hundred twenty-seven woman-infant sets for whom antepartum CD4+ levels were
      available, the infant's human immunodeficiency virus infection outcome was known,
      and the duration of ruptured membranes could be determined were included in this
      analysis. RESULTS: Thirty of the 127 evaluable infants (24%) were infected. Women
      with low CD4+ levels (< 20%) were significantly more likely to transmit the virus
      if rupture of membranes was > or = 4 hours (relative risk 4.53, 95% confidence
      interval 1.14 to 1.81, p = 0.02). The same association was not observed among
      women with higher CD4+ levels (relative risk 1.11, 95% confidence interval 0.52
      to 2.69, p = 0.69). No association with the duration of labor or mode of delivery
      was seen. CONCLUSIONS: In this urban North American cohort women with low CD4+
      levels were significantly more likely to transmit human immunodeficiency virus to
      their offspring if the duration of rupture of membranes was > or = 4 hours.

PMID- 7645639
TI  - Factors associated with preterm birth in Cardiff, Wales. I. Univariable and
      multivariable analysis.
AB  - OBJECTIVE: Our purpose was to examine the associations of demographic, social,
      and medical factors with risk of preterm birth. STUDY DESIGN: By use of the
      Cardiff Births Survey, a large database of largely homogeneous (white) births in
      Wales, multivariable analysis by logistic regression examined the relative
      importance of risk variables associated with preterm birth. RESULTS: Significant
      independent associations with preterm birth were found (in decreasing order of
      magnitude) for late pregnancy bleeding, preeclampsia-proteinuria, low maternal
      weight, low maternal age, early pregnancy bleeding, history of previous
      stillbirth, smoking, high parity, low or high hemoglobin concentration, history
      of previous abortion, low social class, bacteriuria, and nulliparity. CONCLUSION:
      In this population demographic, social, and medical characteristics of the
      pregnancies showed significant associations with preterm birth.

PMID- 7645640
TI  - Factors associated with preterm birth in Cardiff, Wales. II. Indicated and
      spontaneous preterm birth.
AB  - OBJECTIVE: Our purpose was to examine and contrast associations of risk factors
      with spontaneous preterm birth and indicated preterm birth. STUDY DESIGN:
      Separate multiple logistic regression analyses were performed of indicated and
      spontaneous preterm births in a large database of births in Cardiff, Wales.
      RESULTS: Spontaneous preterm births were associated with young maternal age, low
      maternal weight, low or high parity, previous abortion, smoking, and early
      pregnancy bleeding. Indicated preterm births were associated with older age, low
      weight, previous stillbirth, bacteriuria, and early pregnancy bleeding.
      CONCLUSION: Spontaneous and indicated preterm births have different overall
      profiles of association with pregnancy risk factors.

PMID- 7645641
TI  - Ultrasonographically guided intrauterine contraceptive device removal before
      chorionic villus sampling.
AB  - OBJECTIVE: Management of a retained intrauterine contraceptive device with no
      visible string during early pregnancy presents a dilemma. Because these devices
      are frequently used by multiparous women, it is not unusual that many women with
      retained devices are also of advanced maternal age. We describe our experience
      with ultrasonographically guided first-trimester retrieval of an intrauterine
      contraceptive device in conjunction with chorionic villus sampling. STUDY DESIGN:
      Patients with a first-trimester pregnancy and a retained intrauterine
      contraceptive device where no string was visible were offered
      ultrasonographically guided retrieval of the device. If the patient had genetic
      risks and desired prenatal diagnosis, chorionic villus sampling was offered at
      the same office visit. RESULTS: Six patients underwent intrauterine contraceptive
      device retrieval, under continuous ultrasonographic guidance, by use of an
      intrauterine contraceptive device hook. All patients had a posterior or fundal
      device. One patient had two in situ: a Lippes Loop (Ortho Pharmaceutical Corp.,
      Raritan, N.J.) removed by its string and a Cu-7 (G.D. Searle & Co., Chicago)
      removed under ultrasonographic guidance. The remaining five patients had a Cu-7.
      Four of six patients had chorionic villus sampling performed immediately after
      the intrauterine contraceptive device removal and one patient had chorionic
      villus sampling 3 weeks later. There were two losses in our series: one after a
      lengthy procedure and one before documented viability. All infants were
      structurally normal and born at term. CONCLUSION: First-trimester
      ultrasonographically guided retrieval of a retained intrauterine contraceptive
      device may be safely performed in conjunction with chorionic villus sampling.

PMID- 7645643
TI  - New perspectives for the effective treatment of preterm labor.
AB  - Preterm birth (before 37 completed weeks of gestation) continues to account for
      the vast majority of neonatal morbidity and mortality. The incidence of preterm
      birth can be reduced by appropriate social interventions and antenatal care.
      Currently available tocolytic agents suffer from low uterospecificity and prolong
      pregnancy only marginally, although postponement of birth by a few days may be of
      some value. Further progress is needed in at least four areas: prevention of
      preterm labor; identification of preterm labor; selection of candidates for
      tocolysis, and treatment of preterm labor. Effective, early treatment of
      vaginosis offers particular promise for the prevention of preterm labor and
      identification of specific biochemical markers will facilitate early detection of
      this process. Oxytocin antagonists offer greater specificity than current
      tocolytics and can be expected to show improved efficacy and risk profiles. Such
      compounds will allow more effective treatment of preterm labor with a lower risk
      of side effects.

PMID- 7645642
TI  - Amniotic fluid interleukin-6: correlation with upper genital tract microbial
      colonization and gestational age in women delivered after spontaneous labor
      versus indicated delivery.
AB  - OBJECTIVE: Our purpose was to determine whether amniotic fluid interleukin-6 is
      increased and inversely proportional to gestational age in women with
      chorioamnion colonization and spontaneous labor versus women delivered for
      medical or obstetric indications. STUDY DESIGN: The chorioamnion and amniotic
      fluid were cultured at cesarean delivery for aerobic and anaerobic bacteria,
      fungi, mycoplasmas, Chlamydia trachomatis and Trichomonas vaginalis in 269 women
      with singleton gestations with intact membranes. The amniotic fluid interleukin-6
      concentration was also determined. RESULTS: Amniotic fluid interleukin-6 levels
      were (1) higher in women with spontaneous labor versus those with indicated
      deliveries (15.8 +/- 5.0 vs 2.2 +/- 0.2 ng/ml, p = 0.01), (2) inversely
      proportional to gestational age in women with spontaneous labor (< 34 weeks: 47.4
      +/- 18.0 ng/ml vs > or = 34 weeks: 8.7 +/- 4.1 ng/ml, p = 0.001) but not in women
      with indicated deliveries (1.5 +/- 0.4 vs 2.4 +/- 0.3 ng/ml), (3) higher in women
      with a positive versus a negative chorioamnion (15.1 +/- 4.8 vs 3.0 +/- 0.8
      ng/ml, p < 0.001) or amniotic fluid (17.4 +/- 7.7 vs 3.8 +/- 0.9 ng/ml, p <
      0.001) culture, and (4) higher in women with a negative amniotic fluid but
      positive chorioamnion culture compared with women in whom both cultures were
      negative (10.0 +/- 4.4 vs 3.0 +/- 0.9 ng/ml, p = 0.002). CONCLUSIONS: Amniotic
      fluid interleukin-6 levels are (1) higher and inversely proportional to
      gestational age in women with intact membranes and spontaneous labor versus
      indicated deliveries, (2) higher in women with one or more microorganisms in the
      chorioamnion or amniotic fluid, and (3) reflective of chorioamnion microbial
      colonization, even when the amniotic fluid culture is negative, and may be a
      useful clinical marker for infection-mediated preterm labor.

PMID- 7645644
TI  - Diagnosis of the respiratory distress syndrome by amniocentesis. 1971.

PMID- 7645645
TI  - Recognition of depression in obstetric/gynecology practices.
AB  - Depression is a common and serious health problem that occurs twice as often in
      women as in men. The lifetime prevalence of major depression in women is
      estimated to be as high as 21%. Although less severe and less common, mild
      depression and dysthymia (chronic mild depression) can cause functional
      disability and require treatment. Regardless of severity or duration, depression
      can be difficult to recognize because it frequently is masked by complaints that
      accompany other common obstetric and gynecologic illnesses and events. This
      article reviews the various depressive disorders in women with a focus on
      presentations that occur in obstetric and gynecologic practice.

PMID- 7645646
TI  - Women at risk for postpartum-onset major depression.
AB  - There is considerable evidence that the childbearing years represent a time when
      women are highly vulnerable to developing mood disorders. Prospective, cross
      sectional, and retrospective studies have demonstrated that more than 10% of new
      adult mothers will experience a major depressive episode during the first
      postpartum year. Changes in the health care delivery system will result in
      increased pressure on the obstetrician/gynecologist to identify and treat women
      with postpartum-onset depression. Despite shortcomings in the available
      literature, prospective studies have identified risk factors for developing
      postpartum depression. Furthermore, the clear overlap between the normal sequelae
      of childbirth and the symptoms of major depression, including alterations in
      sleep, energy, libido, appetite, and body weight, underscores the need to develop
      guidelines for early identification. We furnish a brief overview of postpartum
      mood disorders with a primary focus on the antenatal and postnatal risk factors
      for developing postpartum depression. Based on the extent literature and our
      clinical experience, a set of recommendations for early identification and
      treatment is provided.

PMID- 7645647
TI  - Hormones and depression: what are the facts about premenstrual syndrome,
      menopause, and hormone replacement therapy?
AB  - The diagnosis, epidemiology, etiology, and treatment of premenstrual syndrome are
      reviewed. A relationship between depression and premenstrual syndrome is
      suggested by the increased prevalence of prior depressive episodes in women with
      premenstrual syndrome, common neurotransmitter and chronobiologic abnormalities,
      and the successful treatment of premenstrual syndrome with regimens used for
      depression. The relationship between menopause and depression is not clearly
      defined, but the perimenopausal years may be a time of increased depression for
      women who are at risk for depressive recurrences. The role of hormone replacement
      treatments in either ameliorating or promoting depression in menopausal women is
      a subject for future studies.

PMID- 7645648
TI  - Gender differences in depression in primary care.
AB  - OBJECTIVES: To determine gender differences in the frequency and manifestation of
      depression in primary care. STUDY DESIGN: PRIME-MD, a new assessment tool, was
      tested in 1000 patients as an aid to diagnose depression in primary care
      patients. Answers to a self-assessment questionnaire completed by patients
      determined whether physicians administered the mood module in the Clinician
      Evaluation Guide to diagnose depression. Functional status was assessed with the
      Medical Outcomes Study Short Form (SF-20). RESULTS: More women than men were
      diagnosed as having a mood disorder (31% vs 19%; p < 0.01), and an antidepressant
      was newly prescribed only for women (p < 0.001). There were no gender differences
      in physician ratings of patients' health, but women rated their health
      significantly more poorly than did men. Similarly, functional impairment scores
      were significantly lower in women than in men. CONCLUSIONS: Women are much more
      likely than men to have depressive disorders, and when these disorders are
      diagnosed, to receive a prescription for antidepressant medication. Further
      research is needed to determine why women seem to suffer disproportionately from
      symptoms of depression and signs of functional impairment.

PMID- 7645649
TI  - Advances in the management of depression: implications for the
      obstetrician/gynecologist.
AB  - The selection of an appropriate medication is important for successfully treating
      depression in women. Although antidepressants do not differ in their efficacy for
      the treatment of major depression, they do differ in their side effect profiles,
      toxicity, and mechanisms of action. Tricyclics, heterocyclics, and newer agents
      such as bupropion, fluoxetine, paroxetine, sertraline, and venlafaxine are used
      most commonly to treat depression in women. The dosages, side effects,
      indications, and precautions for these antidepressants are reviewed. Factors
      affecting selection of a particular antidepressant, as well as the general
      management of depression in women, are discussed.

PMID- 7645650
TI  - The accuracy of prenatal ultrasonography in detecting congenital anomalies.

PMID- 7645651
TI  - Unwarranted prenatal intervention.

PMID- 7645652
TI  - Do menopause and hormonal replacement therapy influence body cell mass and body
      fat mass?

PMID- 7645653
TI  - Postdates is not postmature.

PMID- 7645654
TI  - Randomized comparison of a new estradiol-releasing vaginal ring versus estriol
      vaginal pessaries.

PMID- 7645655
TI  - Amnioinfusion and the intrauterine prevention of meconium aspiration.

PMID- 7645656
TI  - The current paradigm shift in American medicine.

PMID- 7645657
TI  - Severe preeclampsia and antioxidant nutrients.

PMID- 7645658
TI  - Ureteral anastomosis with the Unilink system.

PMID- 7645659
TI  - Adenomyosis must be considered in patients with menorrhagia and a normal
      appearing cavity on hysteroscopy or ultrasonography.

PMID- 7645660
TI  - There is more to life than putting on your pants.

PMID- 7645661
TI  - Performance of older adults with and without cerebrovascular accident on the test
      of visual-perceptual skills.
AB  - OBJECTIVES: The purposes of this study were to (a) investigate whether older
      subjects with brain damage score lower on the Test of Visual-Perceptual Skills
      (TVPS) than control subjects without brain damage matched for age and education,
      (b) determine the demographic effects on test performance in both groups, and (c)
      determine the capacity of TVPS in identifying visual-perceptual deficits in
      adults with brain damage. METHOD: The study sample consisted of 22 subjects with
      cerebrovascular accident (CVA) and 155 subjects who were neurologically intact
      (control group). The TVPS was administered individually to each subject. Raw
      scores (total response time and accuracy) were analyzed to generate descriptive
      statistics. Other statistical analysis included analysis of variance, analysis of
      covariance, discriminant analysis, and Pearson product-moment correlations.
      RESULTS: There were significant between-group differences on all TVPS measures,
      with control subjects performing better than subjects with CVA. Age was shown to
      affect performance on most subtests of the TVPS in the control group. Education
      had significant influence over each measure, whereas gender differences were
      significant only in two subtests. No demographic effects were found in the group
      with CVA. The total TVPS accuracy score was the most powerful discriminator
      between the two groups, correctly classifying 74.4% of the subjects. Finally, the
      total accuracy score inversely correlated with total time score. CONCLUSION: The
      TVPS may be useful in screening for visual-perceptual impairments in adults with
      CVA. Age, gender, and educational level have no significant impact on the
      magnitude of visual-perceptual dysfunctions.

PMID- 7645662
TI  - Performance of Americans and israelis with cerebrovascular accident on the
      Loewenstein Occupational Therapy Cognitive Assessment (LOTCA).
AB  - OBJECTIVE: The Loewenstein Occupational Therapy Cognitive Assessment (LOTCA)
      measures the cognitive performance of persons with cerebrovascular accident
      (CVA). Although this assessment was developed and standardized in Israel, it is
      frequently used in the United States. The purpose of this study was to identify
      whether differences in performance on the LOTCA existed between Americans and
      Israelis who have had strokes. Additionally, this study was designed to compare
      the performance of persons with right CVA with the performance of persons with
      left CVA because the normative data for the LOTCA does not include separate
      information for these two groups. METHOD: The LOTCA was administered to 25
      Americans with CVA (19 right CVA and 6 left CVA) and 56 Israelis with CVA (26
      right CVA and 30 left CVA). RESULTS: On the majority of LOTCA subtests, there
      were no significant differences between American and Israeli subjects. Only one
      subtest, Orientation to Time, revealed significant differences between Americans
      and Israeli subjects both for subjects with right CVA and subjects with left CVA.
      Examination of subjects with right CVA versus subjects with left CVA also
      indicated few differences. Only one subtest, Pegboard Construction, revealed
      significant differences between subjects with right CVA and subjects with left
      CVA for both American and Israeli subjects. CONCLUSION: The LOTCA is an
      appropriate tool for occupational therapists to use in assessing Americans who
      have had strokes. In addition, for the most part, the subtests of the LOTCA
      assess cognitive-perceptual abilities that are not specific to the right or left
      cerebral hemisphere.

PMID- 7645663
TI  - Validity of the Behavioral Inattention Test (BIT): relationships with functional
      tasks.
AB  - OBJECTIVES: The Behavioral Inattention Test (BIT) is a standardized assessment
      for unilateral visual neglect. It comprises six conventional and nine behavioral
      subtests. The purpose of this study was to add to the validation of the
      behavioral subtests. METHOD: Forty Israeli subjects with right cerebrovascular
      accident (CVA), from both day center and hospital settings, were evaluated on
      three measures: the BIT, performance tasks, and a checklist of activities of
      daily living (ADL). RESULTS: Seven of the nine BIT behavioral subtests
      differentiated significantly between subjects with visual neglect and those
      without neglect; six of the nine subtests correlated significantly with parallel
      performance tasks or ADL checklist items. CONCLUSION: These results support the
      construct and predictive validity of most of the BIT behavioral subtests as
      functional measures of unilateral neglect, thus, the BIT is recommended for use
      by occupational therapists. Inclusion of a relative score for right and left
      omissions within the BIT is recommended.

PMID- 7645664
TI  - The effect of environmental regulations on postural control after stroke.
AB  - OBJECTIVES: The primary objective of this study was to examine the effect of
      environmental predictability on postural control after stroke. A reaching task
      for seated subjects was used as the postural perturbation. Trajectory stability
      (the pathway followed by the subject's body center for pressure with respect to
      time during the reaching task) was used as the index of postural control. It was
      hypothesized that trajectory stability would be greater under predictable
      conditions. METHOD: A specially designed electromechanical system was used to
      measure the trajectory stability ratios for 100 subjects, 50 with poststroke
      hemiplegia and 50 who had not had stroke. All subjects completed a task that
      required reaching to the left versus reaching to the right, under predictable
      versus unpredictable conditions. Postural control was measured via a trajectory
      instability ratio in both the anterior-posterior and medial-lateral planes.
      RESULTS: Although the effect of predictability on postural control was
      significant, it was not as hypothesized for both groups. There was greater
      trajectory stability under unpredictable conditions when reaching to the right as
      measured in both the anterior-posterior and medial-lateral planes and when
      reaching to the left as measured in the medial-lateral plane. CONCLUSION: These
      findings refute the assumption of the hierarchical, predictable-to-unpredictable
      environment model for postural control evaluation and treatment. The relationship
      between information processing demands and postural skill is probably more
      complex than the simple linear association implied. Perhaps the two conditions,
      predictable and unpredictable, should be worked on concurrently, not
      sequentially.

PMID- 7645665
TI  - Validity of clinical measures of shoulder subluxation in adults with poststroke
      hemiplegia.
AB  - OBJECTIVES: Shoulder subluxation after cerebrovascular accident has been
      associated with chronic pain, orthopedic complications, peripheral nerve damage,
      and autonomic dysfunction. Clinical diagnosis and gradation of subluxation is
      problematic due to the lack of precision in frequently used measures. The
      objective of this study was to assess the validity of clinical techniques used to
      assess inferior subluxation of the hemiplegic shoulder by comparing these
      techniques with radiographic measurement. METHOD: In 20 male subjects with
      hemiplegia, the presence, type, and degree of subluxation was assessed with three
      clinical measures: palpation, arm length discrepancy, and thermoplastic jig
      measurement. Anterior-posterior X rays of the hemiplegic shoulder were taken
      after clinical examination. RESULTS: Spearman rank correlation coefficients
      between the X rays and the three clinical measures were relatively low. Palpation
      had the highest correlation (rs = .76), followed by arm length discrepancy (rs =
      .46), and thermoplastic jig measurement (rs = .42). CONCLUSION: These findings
      provide cautious optimism about using these clinical measures to identify
      subluxation. Although detection was best with palpation, the likely inability to
      determine clinical overcorrecting of subluxation makes use of palpation alone
      suspect. Improved techniques of arm length measurement may provide a solution to
      this problem. These findings further necessitate that improved procedures for
      clinical assessment of subluxation be developed.

PMID- 7645666
TI  - The effects of Dynavision rehabilitation on behind-the-wheel driving ability and
      selected psychomotor abilities of persons after stroke.
AB  - OBJECTIVE: Many conventional rehabilitation exercises, such as pencil-and-paper
      and computer tasks, may not train perceptual and motor skills as applied to a
      complex, multiskill activity such as driving. The present study examined the
      usefulness of the Dynavision apparatus for driving-related rehabilitation. The
      Dynavision was designed to train visual scanning, peripheral visual awareness,
      visual attention, and visual-motor reaction time across a broad, active visual
      field. METHOD: Ten persons with a cerebrovascular accident participated in the
      study. All had failed behind-the-wheel driving assessments. Subjects participated
      in a 6-week Dynavision training program using exercises designed to impose
      various motor, perceptual, and cognitive demands. RESULTS: Dynavision training
      resulted in significantly improved behind-the-wheel driving assessments as
      compared to expected outcomes. Comparisons between pretests, posttests, and
      follow-up tests on a number of Dynavision, response, and reaction time variables
      showed significant improvements and maintenance effects. Dynavision performance,
      and, to a lesser extent, choice visual reaction and response times, were found to
      differentiate between persons assessed as safe and unsafe to drive, and between
      older and younger drivers. Subject self-reports suggested that a variety of
      training-related improvements had occurred in everyday functioning. CONCLUSION:
      Dynavision training shows some rehabilitative promise for improving driving and
      basic psychomotor skills. Future research on the benefits and limitations of this
      apparatus should use finer laboratory skill measures and more comprehensive tests
      of driving and daily functioning to assess more thoroughly skill improvements in
      persons after stroke.

PMID- 7645667
TI  - Visual perception and praxis in adults after stroke.
AB  - OBJECTIVES: The purpose of this study was to examine the performance of persons
      with right cerebrovascular accident (RCVA) and persons with left cerebrovascular
      accident (LCVA) on a variety of measures of praxis and visual perception in order
      to examine the relative contributions of the left and right cerebral hemispheres
      to praxis and perception. METHODS: Forty-five subjects, 15 with RCVA, 15 with
      LCVA, and 15 without CVA (control subjects), were tested on three tests of praxis
      praxic production, gesture comprehension, and gesture discrimination-and selected
      tests of visual perception, including the Judgement of Line Orientation Test, the
      Motor Free Visual Perception Test, the Hooper Visual Organization Test, and the
      Line Bisection Test. RESULTS: Subjects in both groups with CVA performed more
      poorly on all of the tests than did control subjects. The group with LCVA
      performed most poorly on tests of gesture comprehension and praxis production,
      whereas the group with RCVA performed most poorly on tests of gesture
      discrimination and visual perception. CONCLUSION: These findings suggest that
      both the right and left cerebral hemispheres contribute to different aspects of
      praxis. Elements of visual perception may be related to gesture comprehension,
      gesture discrimination, and praxis production in adults who have had stroke.
      These findings have clinical implications regarding instructional style and
      perceptual and praxic training.

PMID- 7645668
TI  - Relation of perceptual and body image dysfunction to activities of daily living
      of persons after stroke.
AB  - Perceptual and body image disturbances are common sequelae in persons who have
      had stroke. There is much evidence to substantiate a relationship between
      impaired perceptual functioning and impaired functioning in activities of daily
      living (ADL). In regard to body image dysfunction, the linking of unilateral
      neglect and poor ADL functioning has been widely examined; however, the
      relationship of other body image disturbances, such as somatoagnosia, to ADL has
      received little examination. Research on the above relationships are reviewed in
      this article. The Behavioral Inattention Test and Arnadottir OT-ADL
      Neurobehavioral Evaluation are discussed as two assessments that determine
      perceptual and body image dysfunction through ADL. The literature on intervention
      for perceptual and body image dysfunction in relation to ADL primarily concerns
      the difference between the restorative and functional retraining approaches and
      treatment suggestions. Because specific gaps are noted in this area of study,
      future research ideas are suggested.

PMID- 7645670
TI  - Quantifying phalangeal curvature: an empirical comparison of alternative methods.
AB  - It has been generally assumed and theoretically argued that the curvature of
      finger and toe bones seen in some nonhuman primates is associated with cheiridial
      use in an arboreal setting. Assessment of such curvature in fossil primates has
      been used to infer the positional behavior of these animals. Several methods of
      quantifying curvature of bones have been proposed. The measure most commonly
      applied to phalanges is that of included angle, but this has come under some
      criticism. We consider various other approaches for quantifying phalangeal
      curvature, demonstrating that some are equivalent to use of included angle, but
      that one--normalized curvature moment arm (NCMA)--represents a true alternative.
      A comparison of NCMA to included angle, both calculated on manual and pedal
      proximal phalanges of humans, apes, some monkeys, and the Hadar fossils, revealed
      that these two different measures of curvature are highly correlated and result
      in very similar distributional patterns.

PMID- 7645669
TI  - A task-oriented approach to the treatment of a client with hemiplegia.

PMID- 7645671
TI  - Limb joint surface areas and their ratios in Malagasy lemurs and other mammals.
AB  - Surface areas of humeral and femoral heads scale largely as a function of body
      size. However, differences in the relative sizes of these articular surfaces are
      correlated with differential joint mobility and force transmission through fore-
      and hindlimbs. They can therefore assist interpretation of the positional
      behavior of extinct species. In this paper, we document variation in ratios of
      humeral head surface area to femoral head surface area among extant primates and
      other mammals. We then examine a group of extinct primates: the subfossil lemurs
      of Madagascar. Many Malagasy lemurs, including some giant extinct species with
      very long forelimbs and short hindlimbs, have relatively small humeral heads and
      large femoral heads. We explore the adaptive implications of this pattern.

PMID- 7645672
TI  - Genomic reorganization and disrupted chromosomal synteny in the siamang
      (Hylobates syndactylus) revealed by fluorescence in situ hybridization.
AB  - We employed in situ hybridization ("chromosome painting") of chromosome-specific
      DNA libraries of all human chromosomes to establish homologies between the human
      and siamang karyotypes (Hylobates syndactylus, 2n = 50). Numerous intra- and
      interchromosomal rearrangements have led to a massive reorganization of the
      siamang karyotype. There have been a minimum of 33 translocations. The 24 siamang
      autosomes are composed of 60 recognizable segments that show DNA homology to
      regions of the 22 human autosomes. Only two autosomes have not been involved in
      translocations. The siamang presents a case, in a primate closely related to
      humans, in which chromosome morphology and synteny are highly disturbed in a
      manner similar to that encountered among rodents.

PMID- 7645673
TI  - Positional behavior in five sympatric Old World monkeys.
AB  - Observations of positional behavior and habitat use were recorded on focal
      individuals of five species of Old World monkeys at Kibale Forest, Uganda,
      through the dry season of 1990 and 1991. Cercopithecus ascanius, Cercopithecus
      mitis, Cercocebus albigena, Colobus badius, and Colobus guereza commonly utilize
      five similar types of positional behavior (i.e., quadrupedalism, leaping,
      climbing, sitting, and standing), but in varying frequencies and situations. As a
      group, colobines use oblique supports and leap more often, and cover greater
      linear distances during leaps than do cercopithecines. Colobines also prefer to
      sit (about 90% of all postures), while cercopithecines stand more frequently.
      Body size differences between the sexes of a species are not reflected in
      positional behavior. The two small-bodied species climb more and leap less often
      than the three larger species, which is the reverse of what we would expect.
      Leaping is the most common method of crossing open spaces within the canopy; but
      most spatial gaps and leaps are over short distances, usually one meter or less.
      All five species, regardless of body size or the availability of forest supports,
      prefer medium-sized supports. Incorporating our work from Uganda with previous
      investigations of positional behavior reveals few consistent trends with respect
      to body size or habitat use across primates.

PMID- 7645674
TI  - Brief communication: Tigaran (Point Hope, Alaska) tooth drilling.
AB  - In a sample of 48 adult Tigarans (1300-1700 A.D.) from Point Hope, Alaska, 33
      exhibited various degrees of periodontal disease, which, in 25, resulted in tooth
      loss (Schwartz, unpublished data). Although extreme examples of tooth wear were
      prevalent in the sample, carious infection was noted in only one individual, in
      whom the lower central incisors (I1S) had been affected. In the left I1,
      infection had spread through the root's apex into the alveolar bone, causing an
      abscess. The buccal (labial) side of the root of this tooth, just below the
      crown, bears a shallow, relatively flat-bottomed depression, with a small
      perforation into, as well as a second hole that fully penetrates, the root canal.
      Both of these features appear to have been produced by an implement, and, as they
      are associated with a diseased tooth, and ritualistic tooth shaping or drilling
      of any sort was, and is, not practiced among Arctic groups, their purpose was
      probably therapeutic. As such, this specimen appears to represent a case of
      precontact New World Arctic dentistry.

PMID- 7645675
TI  - On a test of the multifactorial aging method by Bedford et al. (1993).

PMID- 7645676
TI  - A low distribution volume as a determinant of efficacy and safety for histamine
      (H1) antagonists.

PMID- 7645677
TI  - Influence of H1-receptor antagonists on adhesion molecules and cellular traffic.

PMID- 7645679
TI  - Clinical studies with cetirizine in allergic rhinitis and chronic urticaria.

PMID- 7645678
TI  - A comparison of the pharmacodynamics of H1-receptor antagonists as assessed by
      the induced wheal-and-flare model.

PMID- 7645680
TI  - Nonclassical clinical indications for H1-receptor antagonists in dermatology.

PMID- 7645681
TI  - The use of anti-H1 drugs in mild asthma.

PMID- 7645682
TI  - Psychometric aspects of antihistamines.

PMID- 7645684
TI  - A new classification of H1-receptor antagonists.

PMID- 7645683
TI  - Specific review of the psychometric effects of cetirizine.

PMID- 7645685
TI  - [Regulatory factors of the ovarian function].

PMID- 7645686
TI  - [Endemic of AIDS in Spain. Commentaries on official statistics].

PMID- 7645687
TI  - [Breast feeding at present].

PMID- 7645688
TI  - [Increase of tuberculosis and coinfection with AIDS].

PMID- 7645689
TI  - [Medical publication as a social health problem].

PMID- 7645690
TI  - [Controversies about luteal phase defects].

PMID- 7645691
TI  - [Tinnitus: current state].

PMID- 7645692
TI  - [Controversies in surgery of esophageal cancer].

PMID- 7645693
TI  - Intensive care medicine in the reformed National Health Service.

PMID- 7645694
TI  - Laryngeal mask airway insertion using cricoid pressure and manual in-line neck
      stabilisation.
AB  - Forty patients were studied to assess the ease of insertion of the laryngeal mask
      in the simultaneous presence of cricoid pressure and manual in-line stabilisation
      of the neck. This was compared with the normal technique of laryngeal mask
      insertion in the same patients. Fibreoptic views obtained through the laryngeal
      mask were documented on each occasion. The device was inserted successfully in
      all 40 patients when the head was kept in the normal position. This was achieved
      on the first attempt in 33 patients. When cricoid pressure and manual in-line
      neck stabilisation were applied, successful laryngeal mask insertion was only
      possible in 29 patients, with correct placement at the first attempt in 14
      patients. The differences were statistically significant (p < 0.001). When
      cricoid pressure and neck stabilisation were applied, vocal cord visualisation
      through the laryngeal mask with a fibreoptic bronchoscope was only possible in 15
      patients. With the head in the normal position the vocal cords were seen in 33
      patients. The implications of these results are discussed with respect to the
      role of the laryngeal mask in the multiply injured patient.

PMID- 7645695
TI  - The role of continuous positive airway pressure during weaning from mechanical
      ventilation in cardiac surgical patients.
AB  - We investigated the effects of providing patients with continuous positive airway
      pressure during a short weaning period from mechanical ventilation to extubation.
      Following elective primary aortocoronary bypass surgery employing cardiopulmonary
      bypass, 80 patients received intermittent positive pressure ventilation for 5 h.
      At the end of this time patients were randomly allocated to one of the following
      three groups for a 2 h period of spontaneous respiration prior to extubation:
      group CPAP0 = T-piece circuit (n = 27); group CPAP5 = 5 cmH2O of continuous
      positive airway pressure (n = 27); group CPAP10 = 10 cmH2O of continuous positive
      airway pressure (n = 26). Following extubation, pulmonary gas exchange was
      assessed after 1, 2, 4, and 24 h. All patients had good pre-operative lung
      function. There was a significant increase in the median alveolar-arterial oxygen
      partial pressure difference and a decrease in the oxygenation index in all three
      groups during the period of added inspired oxygen which persisted until 24 h post
      extubation, but there were no differences between the groups. In patients with
      good pre-operative lung function requiring primary aortocoronary bypass surgery,
      the use of continuous positive airway pressure confers no advantage over a simple
      T-piece attachment during the short period of weaning from mechanical ventilation
      to extubation.

PMID- 7645696
TI  - Movement of oral and nasal tracheal tubes as a result of changes in head and neck
      position.
AB  - The tracheas of 20 ASA grade 1 and 2 patients were each consecutively intubated
      with an oral and nasal cuffed tracheal tube. Measurements of tube movement, as
      the position of the head and neck altered, were made with a fibreoptic
      bronchoscope. Both oral and nasal tubes moved an average distance of 15 mm
      towards the carina with head and neck flexion and 8.5 mm away with head and neck
      extension. Movement in both directions occurred with lateral rotation of the
      head. Optimal placement of tracheal tubes can be aided with a single guide mark
      placed 3 cm proximal to the cuff and 8 cm proximal to the distal end, which may
      reduce complications arising from this movement. This is a better method in women
      than inserting a pre-determined length of tracheal tube measured from the lips or
      nares. However, current guide marks vary in their position relative to the cuff
      and tip of the tube.

PMID- 7645697
TI  - Does dead space ventilation always alleviate hypocapnia? Long-term ventilation
      with plain tracheostomy tubes.
AB  - Long-term tracheostomy-ventilated patients have better speech with a cuffless
      tracheostomy tube and a large tidal volume. Moderate day time hyperventilation
      from a pressure-limited ventilator is necessary in these patients to avoid
      hypoxia during sleep due to the variable insufflation leak. This study sought to
      confirm whether a dead space of 3 ml.kg-1 could help to provide normocapnic
      hyperventilation during waking time without causing hypercapnia and hypoxaemia
      during sleep. Transcutaneous blood gas studies were performed on 11 patients with
      high tetraplegia undergoing pressure-limited pulmonary ventilation with room air.
      Recordings were made for 120 min each when awake and asleep, with and without
      dead space. The mean derived arterial PCO2 without the dead space was 2.95 kPa
      awake and 3.21 kPa asleep, whilst the corresponding tensions with dead space were
      3.39 kPa and 3.79 kPa. These small increases associated with the dead space, both
      awake and asleep, were statistically significant. There was a statistically,
      though not clinically significant decrease in oxygen tension when the patients
      without dead space went to sleep. The fact that the carbon dioxide tension was
      higher during sleep when dead space was in situ indicates that, despite the
      insufflation leak in these patients, there is significant rebreathing back
      through the dead space. Amelioration of hypocapnia during waking and sleeping is
      achievable using a dead space extension in these patients.

PMID- 7645698
TI  - Resuscitation skills of trainee anaesthetists.
AB  - We assessed the basic and advanced cardiopulmonary resuscitation skills of 30
      trainee anaesthetists in a simulated exercise. Only one person performed basic
      cardiopulmonary resuscitation as outlined in the 1992 European Resuscitation
      Council guidelines. The management of ventricular fibrillation and asystole were
      correctly carried out by eight (27%) and nine (30%) anaesthetists, respectively.
      Neither the seniority of the anaesthetists nor their postgraduate qualifications
      correlated with their performance level. We conclude that all trainee
      anaesthetists need to undergo regular training and assessment of their
      resuscitation skills.

PMID- 7645699
TI  - The effect of nasal oxygen flow and catheter position on the accuracy of end
      tidal carbon dioxide measurements by a pharyngeal catheter in unintubated,
      spontaneously breathing subjects.
AB  - Reliable recordings of carbon dioxide concentrations during spontaneous
      respiration can be obtained from a catheter positioned in the hypopharynx. The
      present study investigated the possible influence on end-tidal carbon dioxide
      measurement of nasal oxygen administration, position of the sampling catheter and
      mouth breathing. The study demonstrated that not only can reliable capnographic
      tracings be obtained from a thin catheter placed in the unintubated airway, but
      the subject may also receive up to 6 l.min-1 of oxygen via the nasal route
      without interference with the accuracy of the measurements. Furthermore, the
      exact position of the sampling catheter tip in the airway is not critical, which
      means that it may be placed where it causes the patient least discomfort.
      Finally, mouth breathing caused a mean decrease in end-tidal carbon dioxide of
      0.25 kPa compared to nose breathing.

PMID- 7645700
TI  - The TOF-Guard neuromuscular transmission monitor. A comparison with the Myograph
      2000.
AB  - The TOF-Guard neuromuscular monitor uses an accelerometer to measure the response
      to nerve stimulation. In this study, we have compared it to a standard
      mechanomyographic monitor, the Myograph 2000, for neuromuscular monitoring in 28
      subjects. A train-of-four mode of stimulation was used in both cases. The times
      taken for onset of block, and for the recovery of T1 (the first response in the
      train of four) to 25% of control, the time from recovery of T1 from 25-75% and
      for the recovery of the train of four ratio to 0.7 were compared with the two
      monitors. There was a good correlation between the two devices for both onset and
      recovery times. However, differences were highlighted when the data were analysed
      by the method of Bland and Altman. The 95% limits of agreement for the T1
      recovery to 25%, as measured by the TOF-Guard, ranged from 5 min less to 8 min
      more than when measured by the Myograph 2000. For recovery of the train of four
      ratio to 0.7, the limits of agreement were approximately 6 min in either
      direction. The 95% limits for the TOF-Guard measured train of four ratio were
      from 0.47 to 0.99, at the Myograph reading of 0.7. We recommend that information
      from the TOF-Guard and the Myograph 2000 should not be used interchangeably.
      However, the TOF-Guard is likely to improve considerably on tactile evaluation of
      the responses to stimulation.

PMID- 7645701
TI  - An assessment of portable carbon dioxide monitors during interhospital transfer.
AB  - Four portable carbon dioxide monitors were assessed by a mobile intensive therapy
      team during interhospital transfer of critically ill patients. Particular
      attention was paid to practical considerations such as size, battery life and
      ease of use. All the monitors performed well in terms of accuracy but problems
      with size and battery life made some less suitable for use outside hospital.

PMID- 7645702
TI  - The estimation of inspired isoflurane concentration in a low-flow system.
AB  - We have examined the predictability of inspired isoflurane concentration during
      low-flow anaesthesia using a to-and-fro breathing system. Twenty one adult
      patients requiring mechanical ventilation of the lungs during surgery took part
      in this study. Using a fresh gas flow of 2 l.min-1, the ratio of inspired
      isoflurane concentration to isoflurane vaporizer setting was found to be
      approximately 4/5th after 5 min of anaesthesia. The ratio was maintained
      throughout the procedure, except for a few minutes following each change in
      vaporizer setting.

PMID- 7645703
TI  - A fibreoptic laryngoscope for paediatric anaesthesia. A study to evaluate the use
      of the 2.2 mm Olympus (LF-P) intubating fibrescope.
AB  - A technique for the use of the Olympus LF-P as an aid to tracheal intubation, via
      the oral route, in 40 anaesthetised, spontaneously breathing children is
      described. The technique was completely successful in 30 (75%) of the children.
      Complications occurred in the remaining ten (25%); two developed laryngospasm and
      in seven the fibrescope flipped out of the trachea during the initial passage of
      the tracheal tube over the fibrescope. In one child the wrong tracheal tube was
      initially chosen. The two children who developed laryngospasm and three of the
      children in whom the fibrescope flipped out of the trachea required conventional
      laryngoscopy and tracheal intubation. Whilst this technique allowed for training
      in the use of the LF-P in paediatric anaesthesia there were a number of
      complications.

PMID- 7645704
TI  - Metabolic acidosis. A new approach to "neostigmine resistant curarisation". 1962.

PMID- 7645705
TI  - Tracheal occlusion in the prone position in an intubated patient with Duchenne
      muscular dystrophy.
AB  - A 15-year-old boy with Duchenne muscular dystrophy developed complete airway
      obstruction under general anaesthesia when positioned prone for spinal surgery.
      Tracheobronchial compression against vertebral bodies facilitated by a shortened
      sternovertebral distance due to thoracic lordoscoliosis is suggested as the
      cause.

PMID- 7645706
TI  - Severe airway management problems during insertion of a cuffed oesophageal stent.
AB  - A 68-year-old man underwent a general anaesthetic for insertion of an oesophageal
      stent for a tracheo-oesophageal fistula. The authors report the management of
      severe airway problems caused by the insertion of the stent and discuss the use
      of a double lumen tube in this situation.

PMID- 7645707
TI  - Percutaneous dilational tracheostomy. Malposition leading to delayed weaning.
AB  - We report a patient in whom delayed weaning from ventilatory support was caused
      by the malposition of a percutaneous dilational tracheostomy tube. A fold of
      mucosa, identified at tracheoscopy, was found to be the limiting factor, and the
      situation was resolved by removal of the tracheostomy and reintubation. We
      believe that the case supports the routine use of a bronchoscope to check the
      position of the tracheostomy tube.

PMID- 7645708
TI  - The use of protective gloves, the incidence of ampoule injury and the prevalence
      of hand laceration amongst anaesthetic personnel.
AB  - In a study of 97 anaesthetic sessions, the incidence of hand laceration secondary
      to opening glass ampoules was 6% and the prevalence of visible old hand
      laceration 26%. The wearing of gloves for procedures likely to cause
      contamination by human secretions ranged from 35-86%. Overall there was no
      statistically significant difference in glove wearing habits of trainees and
      consultants. In the presence of a visible laceration, glove wearing by trainees
      increased and was significantly higher than that practiced by consultants. There
      were at least 90 procedures performed in 97 sessions during which an anaesthetist
      risked contaminating a visible laceration. It appears that the occupational risk
      of contracting a blood-borne viral infection is still unnecessarily increased by
      anaesthetists not wearing protective gloves for all procedures in which
      contamination may occur.

PMID- 7645709
TI  - Lifting and handling of patients by anaesthetists.
AB  - The process of transferring patients from the operating table was assessed in a
      district general hospital. The survey was conducted in two parts; a confidential
      questionnaire was sent to all members of the department and a month long
      assessment of three anaesthetists' caseload was undertaken. All the anaesthetists
      questioned had scanty knowledge of the relevant manual handling regulations.
      Although 70% of anaesthetists questioned lift and transfer patients on a regular
      basis, none had received any relevant training. Ninety-six percent of patient
      transfers were performed by two staff alone, even though there were five or more
      staff available to assist at 95% of transfers. Difficulty in transferring
      patients occurred in 32% of cases. Improvement of training anaesthetists in safe
      manual handling procedures is recommended.

PMID- 7645710
TI  - Awareness during anaesthesia for implantable cardioverter defibrillator
      implantation. Recall of defibrillation shocks.
AB  - Implantable cardioverter defibrillator implantation is performed under general
      anaesthesia. This report describes awareness or recall in two of 33 patients
      scheduled for implantation. After induction, anaesthesia was maintained using
      continuous infusions of propofol and atracurium and intermittent boluses of
      alfentanil. Propofol was given in the same arm as the implantation side. In these
      two patients propofol flowed out of the bleeding central venous access. To
      minimise the possibility of awareness, we advise that continuous infusions should
      be administered intravenously on the contralateral side to the implantation and
      that neuromuscular blocking agent be given by intermittent bolus injections.

PMID- 7645711
TI  - Comparison between two fibrescopes with different diameter insertion cords for
      fibreoptic intubation.
AB  - Two fibreoptic bronchoscopes with insertion cords of different diameters (3.7 and
      5.0 mm) were compared during fibreoptic intubation in 84 adult patients (ASA 1-2)
      undergoing orotracheal intubation under general anaesthesia. The fibrescope used
      was randomly selected. The incidence of resistance to passage of the tracheal
      tube through the vocal cords was higher using the thinner fibrescope, 14/40 (35%)
      as compared with the thicker fibrescope, 5/44 (11%) (p < 0.05). Intubation failed
      with the thinner fibrescope in 8/40 (20%) of patients, whereas all intubations
      with the thicker fibrescope were successful in six patients after manipulation of
      the tracheal tube (p < 0.01). With the thinner fibrescope manipulation of the
      tracheal tube after impingement led to intubation of the trachea in 6/14 (43%)
      patients. The duration of intubation was significantly shorter with the thicker
      fibrescope (p < 0.05). There were two instances of oesophageal intubation with
      the thinner fibrescope. A fibrescope with a thicker insertion cord is more
      suitable for orotracheal fibreoptic intubation in adult patients.

PMID- 7645712
TI  - Oxygen therapy reduces postoperative tachycardia.
AB  - Concomitant hypoxaemia and tachycardia in the postoperative period is
      unfavourable for the myocardium. Since hypoxaemia per se may be involved in the
      pathogenesis of postoperative tachycardia, we have studied the effect of oxygen
      therapy on tachycardia in 12 patients randomly allocated to blinded air or oxygen
      by facemask on the second or third day after major surgery. Inclusion criteria
      were arterial hypoxaemia (oxygen saturation < or = 92%) and increased heart rate
      (> 90 beat.min-1). Each patient responded similarly to oxygen therapy: an
      increase in arterial oxygen saturation and a decrease in heart rate (p < 0.002).
      Thus, postoperative supplementary oxygen has a positive effect on the cardiac
      oxygen delivery and demand balance.

PMID- 7645713
TI  - A survey of obstetric patients who refuse regional anaesthesia.
AB  - One hundred obstetric patients presenting for elective surgery who had refused
      regional anaesthesia were interviewed just prior to entering the operating room.
      In each case, the reason for refusing a regional technique was recorded. The most
      frequent reasons given were fear of backache (33%) and fear of the needle (28%).
      Anaesthetists should be aware of patients' concerns and be able to discuss the
      relevant issues.

PMID- 7645714
TI  - Contribution by anaesthetists to medical education and training.

PMID- 7645715
TI  - ODAs and anaesthesia rooms: priceless assets.

PMID- 7645716
TI  - Blood pressure measurement using oscillometric finger cuffs.

PMID- 7645717
TI  - Forced-air warming maintains normothermia during orthotopic liver
      transplantation.

PMID- 7645718
TI  - Irrigation fluid absorption in transurethral resection of the prostate.

PMID- 7645719
TI  - Paraplegia and spinal cord ischaemia.

PMID- 7645720
TI  - Anaesthetic considerations in patients with Fraser syndrome.

PMID- 7645721
TI  - Combined analgesic effect of morphine and ketamine.

PMID- 7645722
TI  - Lignocaine gel and the laryngeal mask airway.

PMID- 7645724
TI  - Upwardly mobile minitracheotomy.

PMID- 7645723
TI  - Lignocaine gel and the laryngeal mask airway.

PMID- 7645725
TI  - Tension pneumoperitoneum causing superior vena cava obstruction.

PMID- 7645726
TI  - Portex percutaneous tracheostomy kit.

PMID- 7645727
TI  - Limb circumference in critically ill patients.

PMID- 7645728
TI  - Diathermy frequency shock from faulty pulse oximeter probe.

PMID- 7645729
TI  - Lignocaine test doses to detect intravenous injection.

PMID- 7645730
TI  - Lignocaine test doses to detect intravenous injection.

PMID- 7645731
TI  - Let us re-examine the safety of midwife epidural top ups.

PMID- 7645732
TI  - An unusual cause of a leak from an anaesthetic machine.

PMID- 7645733
TI  - Ketamine and the cerebral circulation.

PMID- 7645734
TI  - The elastic system of a pressure-bearing tendon of the bullfrog Rana catesbeiana.
AB  - Elastic system components have been described in the pressure-bearing tendon of
      the bullfrog, Rana catesbeiana, as a result of histochemical tests and
      transmission and scanning electron microscopy. The tension region was shown to
      possess microfibril bundles, some of which exhibited central deposits of
      amorphous material. The use of ANS-butanol plus fluorescence microscopy
      enormously facilitated the identification of elastic system components in both
      tension and compression regions of the frog tendon. The compression region
      exhibited pre-elastic and mature elastic fibers, which were shown to be
      associated with the surface of the convoluted collagen bundles. Thin fibrils were
      observed in the compression region after ANS treatment. The visceral paratenon
      had an increased number of elastic fibers located between the collagen bundles
      and close to the cells. Congo red plus polarization microscopy failed to impart
      birefringence to the elastic fibers, but they could be identified by their
      intense staining and isotropic appearance against the bright background of
      birefringent collagen fibers. SEM demonstrated the three-dimensional aspects of
      the elastic fibers. They are composed of fibrils of a sinuous nature. The use of
      ruthenium red in the fixative allowed for the observation of an intimate
      association of proteoglycan granules with the microfibril bundles. The elastic
      components identified in the pressure-bearing tendon are assumed to be important
      for the tissue supramolecular organization, especially in the maintenance of the
      convoluted state of the collagen fibers in the compression region and their crimp
      morphology in the tension region. The elastic system must also play an important
      role in the restoration of the resting shape of the tendon after the deformation
      achieved during mechanical stimulation.

PMID- 7645735
TI  - Morphological study of the submucosal and mucosal plexuses of the sheep
      forestomach.
AB  - Submucosal and mucosal nerve plexuses in the ovine forestomach were examined by
      immunohistochemical staining for protein gene-product 9.5 (PGP 9.5) and for S-100
      protein (S-100), using whole-mount specimens that had been prepared by treatment
      with KOH. Nerve fibers of various sizes and glial cells (i.e., Schwann cells and
      satellite cells) were stained with antibodies against PGP 9.5 and S-100
      respectively. The network of the submucosal plexus in the rumen is irregular and
      some nerve bundles in the plexus cross over other bundles. Some of the nerve
      bundles penetrate the ruminal papillae. The submucosal plexus in the reticulum
      consists of a network in the reticular wall and the reticular folds. The
      submucosal plexus in the omasum is also divided into two segments; namely, the
      sublaminar and the intralaminar plexuses. Most of the submucosal ganglion cells
      are unipolar and smooth-surfaced, being located singly or in small groups. A few
      perikarya were detected in the ruminal papillae. The number of perikarya per unit
      surface area is greater in the caudal portion of the omasal lamina (19.32 +/-
      8.62 per cm2). In the mucosal plexuses, a well-developed network of beaded fibers
      with PGP 9.5-like immunoreactivity and a glial framework of S-100 like
      immunoreactivity was observed, in particular in the ruminal, reticular and omasal
      papillae. The intrapapillary nervous networks are interconnected by thin bundles
      of nerves in the interpapillary region. The present results suggest that some of
      the mucosal functions are intrinsically regulated by the submucosal and mucosal
      plexuses in the ovine forestomach.

PMID- 7645736
TI  - Ultrastructure and x-ray microanalytical study of human pineal concretions.
AB  - We examined human pineal concretions and found them to exhibit a multi-layered
      concentric structure consisting of irregularly spaced dense and sparse zones
      containing fine crystals. The hydroxyapatite crystallites were shown to be
      irregularly outlined plate forms (measuring 11-70 nm in their longest dimension
      and 2-10 nm in thickness). At the center of each crystallite a central dark line
      was observed by means of high resolution electron microscopy. The structure and
      size of the crystals were similar to those of dentin and bone. The ground surface
      of the concretions was observed metallurgically by means of an electron probe
      microanalyzer (EPMA). The surface zones of the concretions contained a higher
      concentration of zinc, which seems to play an important role during the
      mineralization process, whereas calcium and phosphorus exhibited higher
      concentrations at the center.

PMID- 7645737
TI  - [Vascularization of the anal sacs in the domestic cat].
AB  - The blood vessels of the anal sac in the domestic cat--A. rectalis caudalis and
      A. perinealis ventralis, from which the former arises--are visceral blood
      vessels. A rectalis caudalis, being the origin of anal sac arteries, facilitates
      the blood supply of the anal sac, while the duct of the anal sac is vascularized
      mainly by branches from the A. perinealis ventralis. Within the anal sac wall,
      the anal sac arteries ramify to become Rr. glandulae holocrinae, Rr. glandulae
      apocrinae as well as branches of a vascular network in the mucosal propria from
      which Rr. epitheliales arise. All of the mentioned rami extend into a close
      meshed capillary network. The venous drainage is facilitated by veins that run
      mainly parallel to the arterial blood vessels.

PMID- 7645738
TI  - A comparative study of the application of scanning acoustic microscopy and
      confocal laser scanning microscopy to the structural assessment of human bones.
AB  - The Scanning Acoustic Microscope (SAM) is used to image mechanical structure and
      to measure the sound velocity in micrometers of in vitro samples from human bone.
      A similar principle is used in confocal laser scanning microscopy. The same
      sample is imaged by both methods and the results compared. We concentrated on the
      SAM, the function of which is described in greater detail. We demonstrate that
      the confocal scanning principle is applied in both microscopes, although
      information about structure differs, depending on the method used.

PMID- 7645739
TI  - Visualization of hydrogen peroxide (H2O2)-production from histamine.
AB  - The cellular and intracellular metabolization sites of the tissue hormone and
      paracrine compound histamine as a source for the indirect and potentially toxic
      or physiological mediator molecule H2O2 are not yet known. Therefore, in the
      present study, histamine was used as the substrate in a cerium-diaminobenzidine
      H2O2-Co procedure to visualize for the first time the oxidative deamination and
      H2O2-production sites of this amine in various laboratory animals. Diamine
      oxidase (DAOX) was shown to be the responsible enzyme. With the exception of
      marmosets, all species could deaminate histamine oxidatively and form H2O2. In
      most species, H2O2 was produced by DAOX from histamine in small intestinal
      enterocytes; in rats H2O2 was generated in all vascular and non-vascular smooth
      muscle cells; in guinea-pigs only smooth muscle cells in the digestive tract and
      uterus and in addition the cardiac and gastric capillary endothelium and hepatic
      sinusoidal endothelium produced H2O2. Furthermore, in some species H2O2 was
      generated by DAOX with histamine as the substrate in certain renal, adrenal and
      splenic cell types. While H2O2-production in enterocytes may derive from luminal
      borne histamine, i.e., from histamine of foreign origin, the formation of H2O2 in
      the other cells suggests endogenous (mast cell, basophilborne) histamine as the
      substrate and H2O2 source.

PMID- 7645741
TI  - Quantitative investigations into the histostructural nature of the human putamen.
      II. The differentiated topological distribution of certain neuron type
      arrangements.
AB  - Several mathematical procedures have been worked out for describing quantitative
      arrangements of neurons, and especially subpopulations of neurons, in the human
      putamen. Visual point field analysis is a newly developed method for the
      qualitative recognition of the fuzzy clustering of types of neurons. Nearest
      neighbourhood analysis is an established procedure in stochastic geometry and
      image analysis. These cluster-analytical methods make possible the determination
      of local neuron topology. They represent an extension and application of the
      point pattern analysis (Diggle 1983), and are used here to calculate the
      statistical significance of certain arrangements of cells. The application of all
      these methods together revealed an interesting neuronal arrangement: type 1
      neurons tend to remain at a certain distance from other type 1 neurons, whereas
      type 6 neurons lie close together.

PMID- 7645740
TI  - Development of a culture system for pure rat neurons: advantages of a sandwich
      technique.
AB  - Primary cell cultures were derived from the cerebral cortices of embryonic rats
      (E 17). Survival of the cultures under serum-free conditions was improved by
      creating a sandwich: a poly-D-lysine-coated coverslip with plated cells was
      placed upside down in plastic culture dishes. Neurite outgrowth was observed
      within three hours after plating, and a neuronal network was established after 24
      hours. The viability of the neurons gradually decreased. However, the cells could
      be cultivated for up to 24 days. Under these conditions the contamination with
      non-neuronal cells was minimized to less than 5%, as evidenced by
      immunohistochemical methods using the well-established cell marker proteins:
      neuron-specific enolase (NSE) as neuronal marker, and vimentin and glial
      fibrillary acidic protein (GFAP) as astroglial markers. Returning the coverslip
      to a normal open face position led to cell death within 24 hours. In order to
      investigate the maturation and differentiation of the cultured nerve cells, we
      looked for synapse formation by staining the synaptic vesicle protein
      synaptophysin (p38). It could be immunostained after three days in vitro (DIV)
      only in the neuronal perikarya, in perikarya and axons after six DIV, and in
      varicosities and contact points between axon terminals and adjacent axons or
      perikarya after 10-12 DIV. It appears that this simple culture method, which (i)
      yields highly enriched (> 95%) neuronal cultures with more than 85% cells
      surviving after five days in vitro, (ii) the absence of non-neuronal cells and
      (iii) the good maturation/differentiation of the cells, may be useful for the
      study of the neurochemical, physiological or regulatory mechanisms involved in
      nerve cell development.

PMID- 7645742
TI  - The distal tendon of the biceps brachii. Structure and clinical correlations.
AB  - The structure and blood supply of 42 distal biceps tendons were investigated by
      means of light and electron microscopy as well as by immunohistochemistry.
      Possible structural causes for the rupture of the tendon are discussed. The
      distal biceps tendon wraps around the radius during pronation of the forearm. In
      this area the tendon is exposed to pressure and shearing forces in addition to
      those caused by tension. Two fibrocartilaginous areas were regularly observed.
      Large chondrocyte-like cells were found inside the fibrocartilage. As an
      expression of strain, the extracellular matrix is rich in acidic
      glycosaminoglycans and stains intensely with toluidine blue at pH 1. Electron
      microscopy showed a granular pericellular matrix that increases in size towards
      the gliding surface. Type I collagen is the main component of the distal biceps
      tendon. Type II collagen is found in tendon fibrocartilage but not in traction
      tendons. The gliding surface of the tendon is made up of reticular fibres that
      are equivalent to type III collagen. Monoclonal antibodies revealed the presence
      of dermatan-sulfate, keratansulfate and chondroitin-4- as well as chondroitin-6
      sulfate. Blood vessels are usually absent in fibrocartilage, as was shown with a
      polyclonal antibody against the basement membrane component laminine. There are
      significant differences between the extracellular matrix of traction and gliding
      tendons, which may be responsible for the location of tendon rupture.

PMID- 7645743
TI  - Comparative anatomy of the vomeronasal cartilage in mammals: mink, cat, dog, pig,
      cow and horse.
AB  - The vomeronasal cartilages of mink, cat, dog, pig, cow and horse were studied by
      dissection, microdissection and by means of series of transverse sections. In all
      the species studied the cartilage is of hyaline type and the medial sheet is well
      defined and perfectly moulded to the adjacent bone. However, interspecies
      differences are apparent in the manner in which the medial sheet associates and
      eventually fuses with the cartilage of the incisive duct; the morphology of the
      horse vomeronasal cartilage is particularly distinctive in this respect. The
      lateral sheet of the vomeronasal cartilage, although always present, has a
      different arrangement in each species studied. Similarly, the gaps in the lateral
      sheet (corresponding to the opening of the vomeronasal organ) differ among the
      species studied in form, location and number.

PMID- 7645744
TI  - [Prenatal development of the mandibular gland and parotid gland in cats].
AB  - The prenatal development of the cat's mandibular and parotid gland was examined
      by means of serial section of 36 cat embryos at 14-62 days of development. Both
      glands were excised from the epithelium of the primitive oral cavity and branched
      up to day 36 of the branching phase into a specific connective tissue. This
      tissue contained besides fine collagenous fibres, a high amount of proteoglycans.
      In the subsequent separation phase, ducts and acini differentiated themselves in
      primitive lobules which were separated by connective tissue. In the prenatal
      differentiation phase, from about day 50 up to birth, intercalated ducts and
      striated ducts were formed. In the acini, mucous and serous cells contained
      different amounts of complex carbohydrates. This secretory component changed
      shortly before birth.

PMID- 7645745
TI  - [Growth of the limb bones in ducks].

PMID- 7645746
TI  - Histological changes in the uterus during postpartum in the mare.
AB  - An histological study of the postpartum period in 29 mares was carried out.
      Uterine biopsies were taken daily during the first 10 days postpartum in a total
      of 87 samples. At day 0, equine endometrium was characterized in the surface by
      the presence of regularly ordered microcaruncles; the stratum spongiosum was
      oedematous and contained distended and scarce glands. Degenerative changes in
      microcaruncles and endometrial glands were present on day 1 postpartum. The
      epithelium of the microcaruncles from 2 to 5 days postpartum showed cytoplasmic
      vacuolization, karyorrhexis and an inflammatory reaction with neutrophils and
      phagocitic cells. On day 7 postpartum, the histology of the endometrium was
      similar to the normal proestrus with cuboidal luminal epithelium and an
      oedematous stromal tissue. The changes are usually completed within days 9 and 10
      postpartum with the histologically typical appearance of estrus in mares.

PMID- 7645747
TI  - Swine hearts: quantitative anatomy of the right ventricle.
AB  - The right ventricle was studied in 75 anatomically normal swine hearts, using, in
      all, nine geometric and volumetric parameters: ventricular-wall thickness, length
      of the right-ventricular inflow and outflow tracts, and volume of the right
      ventricular inflow and outflow tracts. The data for these parameters were
      compared with previously published patterns for human hearts and volumetric data
      were compared with patterns of normality found in human hearts. As in the human
      heart, the ventricular inflow tract in swine hearts was significantly shorter
      than the outflow tract (P < 0.0001).

PMID- 7645748
TI  - [Topography of lymph nodes in the grasscutter (Thryonomys swinderianus, Temminck
      1827)].

PMID- 7645749
TI  - The macroscopic vascular anatomy of the equine ethmoidal area.
AB  - The vascular anatomy of the ethmoidal area in six normal horses and two normal
      ponies was studied using vascular-corrosion casts. The major arterial supply to
      the ethmoidal area stems from an intracranial source. The internal and external
      ethmoidal arteries anastomose on the rostral intracranial surface of the
      cribriform plate to form the arterial ethmoidal rete which arborizes and passes
      through the perforations of the cribriform plate to supply the ethmoid labyrinth.
      A minor arterial supply to the ventral portion of the ethmoid labyrinth stems
      from a small caudal nasal branch of the sphenopalatine artery. Multiple parallel
      venules drain the ethmoid labyrinth rostrally to its apex then join the venous
      drainage from the surrounding sinuses.

PMID- 7645750
TI  - [Light- and electron-microscopic studies of the structure of normal bladder
      epithelium in female swine].
AB  - A light- and electron-microscope investigation was performed to examine the
      normal structure of the porcine urinary bladder. Tissue biopsies were studied
      obtained from 10 healthy female pigs (four weanling pigs, six sows). The bladder
      wall showed a typical stratification consisting of a tunica (t.) mucosae, t.
      submucosae, t. muscularis and t. serosa. The mucosa consisted of an epithelium
      transitionale, a lamina propria, and a lamina muscularis mucosae. The urothelium
      was composed of a basal layer, one or more intermediate layer(s), and a
      superficial layer. The urothelial cells of all layers were connected by
      desmosomes, while tight junctions linked adjacent superficial cells. Surface
      cells were lined by a layer of mucus, which is believed to provide an important
      barrier against bacterial infection. The surface of the superficial cells was
      also characterized by numerous irregularly arranged microplicae. By contrast,
      intermediate cells, which are assumed to be immature cell forms, showed
      microvilli-like structures. When desquamation of superficial cells takes place,
      differentiation of underlying intermediate cells is accompanied by merging of
      microvilli to form microplicae. The morphology of the bladder surface structures
      may play an important role in the ability of bacteria to adhere to the
      urothelium.

PMID- 7645751
TI  - [Development and cell differentiation in the nucleus nervi hypoglossi in cows].
AB  - Based upon light- and electron-microscope examinations, the ontogenetic
      development of the nucleus of cranial nerve XII is documented. At 1-cm crown-rump
      length (CRL), the caudal pole of the nucleus nervi hypoglossi forms a uniform
      cell column with the cornu ventrale of the spinal cord. During this period, its
      caudal area shows signs of cellular degeneration. From 3.5 cm CRL onward, all
      nuclear groups can be identified. At 53 cm CRL, they correspond to the pattern as
      described in the adult brain. Electron-optically, at 2.5 cm and 3.6 cm CRL, the
      nucleus of cranial nerve XII exhibits a close relationship to the matrix layer
      which consists of elements of dark nuclei. The hypoglossus nucleus is composed of
      dark and light cell types. It is the latter type that represents the presumptive
      neuron; it shows an increased ultrastructural differentiation from 2.5 cm CRL
      onward.

PMID- 7645752
TI  - A quantitative study of ganglion cells in the German shepherd dog retina.
AB  - As in the number of mammals, the most prominent feature of the ganglion-cell
      layer in the retina of the German shepherd dog is the sharp increase in the
      density of ganglion cells in the central area. There is an area of maximum
      density and also a 'cat-like' visual streak, located dorsal to the optic disc.
      The isodensity lines of ganglion-cell distribution is roughly concentric. Their
      values vary from 5300-13,000 cells/mm2 in the central area, with the cells
      densely packed, to 1000 cells/mm2 or less in the periphery, where the cells are
      sparsely distributed. There were some individual differences amongst the animals
      studied, although all of them were pure-bred dogs. This suggests that the
      configuration of the retina in the canine species is not only dependent on the
      breed itself but also on some other parameters such as phylogenetic heritage,
      environment, aptitude, lifestyle, or even training.

PMID- 7645753
TI  - [Age-dependent sexual dimorphism of the hypothalamic medial preoptic nucleus in
      swine].
AB  - The medial preoptic nucleus of the porcine hypothalamus is characterized by an
      age-dependent sexual dimorphism in the postnatal period of the development. It
      manifests itself as sexual differences in the density and volume of the
      perikarya. A transient concentration of perikarya in the centre of the medial
      preoptic nucleus, especially distinctive in male piglets, is somewhat similar to
      the 'sexually dimorphic nucleus of the preoptic area' of Gorski, as characterized
      in rats.

PMID- 7645754
TI  - [Histomorphometric and histological investigations of the morphometric effects of
      furazolidone on spermatogenesis in mature rats].
AB  - The antispermatongenic effects of furazolidone on the testes of mature Wistar
      rats were investigated using histological and morphometric methods. The sections
      showed a varying degree of depopulation of the germinal epithelium, a shrinking
      and a deformation of the Tubuli contorti, and an enlargement of the intertubular
      lymphatic sinuses. The strain led to a standstill in the spermatogenesis at the
      primary-spermatocyte stage. After administering furazolidone, the following
      results could be seen: a weight loss of up to 42.1% and a decrease in testes
      volume by up to 30.2%; a decrease in the volume of the nuclei of the Leydig-cells
      by up to 51.6%; a reduction in the diameter, perimeter and area covered by Tubuli
      seminiferi contorti of up to 33.5%, 30.8%, and 53.4%, respectively; an increase
      in the number of Tubuli seminiferi contorti per mm2 by up to 44.8%; a decrease in
      the percentage of Tubuli seminiferi contorti of the total testes tissue by up to
      39.1%.

PMID- 7645755
TI  - The role of the inferior colliculus in a genetic model of audiogenic seizures.
AB  - Previous studies have shown the functional importance of the inferior colliculus
      (IC) for the propagation and initiation of audiogenic seizures in several models
      of epilepsy in rats. A review of the cell types and cytoarchitecture of the IC,
      including its three major subdivisions, is presented. Significant increases in
      GABA levels and the number of GABAergic neurons are found in the central nucleus
      of the IC (ICCN) of genetically epilepsy-prone rats (GEPR-9s) as compared to
      Sprague-Dawley rats that do not display audiogenic seizures. Two independent
      anatomical methods were used to determine the number of GABAergic neurons,
      immunocytochemistry and in situ hybridization. In both types of preparation, the
      labeled cells in the ICCN appeared to be of different sizes but the number of
      small cells with diameters less than 15 microns showed the greatest increase.
      Nissl-stained sections showed that the total number of neurons in the ICCN was
      increased in GEPR-9s and indicated that the increase in GABAergic neurons was not
      due to a change in the phenotype of collicular neurons from non-GABAergic to
      GABAergic. The number of small neurons in Nissl-stained sections of the ICCN was
      shown to correlate with seizure severity in the offspring of crosses made between
      Sprague-Dawley rats and GEPR-9s. Furthermore, the GEPR-3s that display moderate
      seizures showed a significant increase in the number of small neurons in the
      ICCN, and the magnitude of this increase was predicted from this correlation.
      Finally, the use of knife cuts through the midbrain indicated that the ICCN sends
      an important projection to the external nucleus and that this projection plays a
      vital role in the propagation of seizure activity from the site of seizure
      initiation in the ICCN. It remains to be resolved how the increase in small
      GABAergic neurons in the ICCN is responsible for the known pharmacological
      defects observed at GABAergic synapses.

PMID- 7645756
TI  - Pax-1, a regulator of sclerotome development is induced by notochord and floor
      plate signals in avian embryos.
AB  - Pax-1 encodes for a DNA-binding transcriptional activator that was originally
      discovered in murine embryos using a probe from the Drosophila paired-box
      containing gene, gooseberry-distal. We have cloned the avian Pax-1 gene as a
      basis for experimental studies of the induction of Pax-1 in the paraxial
      mesoderm. The amino acid sequence of the paired-domain is exactly the same in the
      quail and mouse, whereas outside the paired-domain there is 61% homology.
      Starting at about the eight-somite stage, quail Pax-1 is expressed in the
      paraxial mesoderm in a craniocaudal sequence. The unsegmented paraxial mesoderm
      and the two most recently formed somites do not express Pax-1. In the epithelial
      somite, the somitocoele cells and the cells of the ventral two-thirds of the
      epithelial wall are positive. As soon as the sclerotome is formed, only a subset
      of sclerotome cells expresses Pax-1. These are the cells that migrate towards the
      notochord to form the perinotochordal tube. Expression then becomes restricted to
      the intervertebral discs, the perichondrium of the vertebral bodies and the
      connective tissue surrounding the spinal ganglia. Additional expression domains
      are found in the scapula and the pelvic region, distinct areas of the head, and
      the epithelium of the second to the fourth visceral pouch. In later stages the
      thymus is positive. In vitro and in vivo experiments show that the notochord
      induces Pax-1 in the paraxial mesoderm, but limb bud mesoderm is not competent to
      respond to notochordal signals. Floor plate is also capable of inducing Pax-1
      expression in sclerotome cells. Our studies show that in competent cells of the
      paraxial mesoderm, Pax-1 is a mediator of signals emanating from the notochord
      and the floor plate.

PMID- 7645757
TI  - Distribution of OMP-, PGP 9.5- and CaBP-like immunoreactive chemoreceptor neurons
      in the developing human olfactory epithelium.
AB  - We have examined the distribution of olfactory marker protein (OMP), protein gene
      product 9.5 (PGP 9.5) and calcium-binding protein D-28k (CaBP) in the olfactory
      epithelium of mid- to late fetal and newborn humans using immunocytochemistry.
      Olfactory chemoreceptor neurons (ORNs) in a 24-week-old female fetus, a 31-week
      old male fetus and a newborn male were examined. OMP-like immunoreactivity (-LI)
      and PGP 9.5-LI were distributed throughout ORNs at all ages. CaBP-like
      immunoreactivity, however, was found only in clustered or isolated fetal ORNs; in
      the newborn, CaBP-LI was seen only in isolated ORNs sparsely distributed
      throughout the OE. These findings demonstrate that human ORNs express OMP-LI
      nearly 4 weeks earlier in development than previously reported. PGP 9.5-LI is
      coincidentally abundant within these cells, suggesting it may have an important
      role in mature ORNs. Because the number of ORNs expressing CaBP-LI decreases
      during perinatal development, CaBP may be important in intracellular calcium
      regulation during ORN growth and maturation in the developing OE.

PMID- 7645758
TI  - Transplantation of postnatal vomeronasal organ in the CNS of newborn rats.
AB  - The present study was conducted to examine the survival and development of
      intracerebral transplanted neonatal rat vomeronasal organs (VNs). Complete
      neonatal (P5-P10) VNs were transplanted into the parietal cortex region of
      littermates and examined at 10-100 days by light microscopy. The VN survived and
      was organized into a series of vesicles lined by respiratory and/or sensory
      epithelia. Sensory neurons grew long axons that fasciculated and invaded the
      surrounding brain parenchyma. The newly developed axons did not prefer a specific
      brain region. The axons developed a complex fiber plexus either at the interface
      between transplant and host tissue or deep within the host brain parenchyma.
      Vomeronasal axons consistently formed glomerular-like structures within the fiber
      plexus. Our results suggest that glomerular formation is not dependent on
      specific target of length of axon development, but rather on a set of
      complementary axons that display mutual recognition.

PMID- 7645760
TI  - Morphological classification and identification of neurons in the inferior
      colliculus: a multivariate analysis.
AB  - In this paper a modern statistical method is applied to an old cell
      classification and identification problem in the central nucleus of the inferior
      colliculus. In a recent computer-based reconstruction study of Golgi-impregnated
      neurons in the rat, two types of cell with flattened dendritic arbors, flat (F)
      and less flat (LF), were defined. Both types contributed to the anisotropic and
      laminar pattern of the nucleus. The classification was based on five
      morphological features of complete dendritic arbors, two assessed visually and
      three numerically. With respect to the latter criteria, the two types were
      classified by preselected cut-off values. The distinction of the two types was
      supported, among other things, by a prevailing spatial segregation into laminar
      and interlaminar compartments. The cell sample was too small, however, to
      validate the classification and segregation definitively. In the present study,
      the classification is tested by the partial least squares regression method which
      is independent of the preselected cut-off values, and is able to handle small
      sample sizes and interdependent variables. In the plots, the F and LF cells are
      clearly separated into two distinct clusters, strongly supporting the distinction
      of the two types. The different density of the two clusters shows that the F
      cells are more homogeneous that the LF cells. The relative importance of the
      classification criteria is also evaluated. The three-dimensional (3D) inspection
      and the 3D convex hull-based form factor were found to be the most powerful
      criteria for identifying the two cell types, while the 2D evaluation of camera
      lucida drawings, a standard method in neuroanatomy, proved to have the least
      predictive value.

PMID- 7645759
TI  - Protein kinase C alpha-, beta- and gamma-subspecies in basal granulated cells of
      rat duodenal mucosa.
AB  - Protein kinase C [cPKC: alpha, beta (beta I, beta II), gamma], a Ca(2+)- and
      phospholipid-dependent enzyme, has been thought to play a critical role in the
      synthesis and secretion of gut hormones in gastrointestinal mucosa. However, the
      localization of PKC has not yet been clarified at the cellular level in the
      gastrointestinal epithelium. The present study was made to identify cPKC
      containing cells immunohistochemically in the rat duodenal epithelium by light
      and electron microscopy and by confocal laser scanning microscopy. Special
      attention was paid to the demonstration of cPKC in basal granulated cells. By
      light microscopy, some duodenal epithelial cells were demonstrated to be
      immunopositive for PKC alpha-, beta- and gamma-subspecies. Their distribution and
      incidence were almost similar to those of cells stained by the silver
      impregnation method of Grimelius. By electron microscopy, profiles of secretory
      granules were found at the basal region of the PKC-immunopositive epithelial
      cells. When the cells were double-immunostained for gastrin, serotonin or
      somatostatin and for PKC alpha-, beta- or gamma-subspecies, these gut hormones
      and PKC subspecies were shown to colocalize as examined by confocal laser
      scanning microscopy. These findings show that cPKC (alpha, beta, gamma) is
      present in basal granulated cells such as G-, EC- and D-cells, presumably playing
      some important role in regulation of gut hormones, including their synthesis
      and/or secretion.

PMID- 7645761
TI  - Morphometric study of collagen maturation in chick compact bone.
AB  - An ultrastructural-morphometric study was carried out on the process of osteoid
      maturation in growing surfaces of parallel-fibered chick bone. The aim was to
      investigate the distribution, size and amount of collagen fibrils (CFs), as well
      as the proteoglycan (PG) content, throughout the osteoid seam and in the adjacent
      bone. The results show that the organic components secreted by osteoblasts
      undergo complete maturation inside the osteoid seam only. Proceeding from the
      secreting plasma membrane of osteoblasts (osteoidogenic surface) towards the
      mineralizing surface, we found that CFs gradually increase in diameter but not in
      number per surface unit. As a consequence, the proportion of osteoid seam
      occupied by CF increases too, at the expense of the interfibrillar substance. PG
      content also decreases inversely in this direction. In the adjacent bone, CF size
      and density do not change significantly with respect to the mature osteoid close
      to the mineralizing surface.

PMID- 7645762
TI  - Number of nucleoli and coiled bodies and distribution of fibrillar centres in
      differentiating Purkinje neurons of chick and rat cerebellum.
AB  - We used differentiating chick and rat Purkinje cells to investigate in homologous
      neurons the influence of the number of nucleolar organizer regions (two in the
      chick and six in the rat) on the behaviour of the nucleolus and coiled bodies. We
      employed specific silver-staining methods on smear preparations and on semithin
      and ultrathin sections. In chick Purkinje cells the number of nucleolar silver
      staining granules increased from 15.7 +/- 3 (mean +/- SD) at embryonic day 13 to
      23.8 +/- 3 at post-hatching day 7. These nucleolar granules were unevenly
      distributed between the two nucleoli of binucleolated cells. Electron-microscopic
      cytochemistry showed that nucleolar granules are equivalent to the fibrillar
      centres with their associated shell of dense fibrillar component. A reduction in
      the number of nucleoli was found during the differentiation of both chick and rat
      Purkinje cells, although in mature cells the average number of nucleoli per cell
      was higher in the chick (1.60) than in the rat (1.07). The number of coiled
      bodies decreased from 1.33 in newborn rats to 0.47 at postnatal day 90 in the
      rat. Coiled bodies were not observed in homologous chick Purkinje cells. The
      dynamic behaviour of nucleoli and coiled bodies during neuronal differentiation
      and the relationship of these two nuclear organelles with the number of nucleolar
      organizer regions is discussed.

PMID- 7645763
TI  - Calcium-containing, smooth-surfaced endoplasmic reticulum and vacuoles in cells
      of the blastopore-forming region during gastrulation of the newt, Cynops
      pyrrhogaster.
AB  - Ultrastructural changes in cells of the blastopore-forming region (BFR) were
      examined during gastrulation of the newt, Cynops pyrrhogaster. Smooth-surfaced
      endoplasmic reticulum (sER), tubular in shape and with two types of vacuole,
      empty vacuoles and multilamellar vacuoles, appeared in cells of the BFR at the
      beginning of formation of the blastopore. The extent of the tubular sER increased
      during formation of the blastopore. With the deepening of the blastoporal groove,
      the tubular sER and multilamellar vacuoles disappeared in cells of the BFR. The
      empty vacuoles increased in number and appeared throughout the cytoplasm of the
      cells in the BFR and the marginal zone as formation of the archenteron
      progressed. Many large empty vacuoles were closely associated with deformed lipid
      droplets. Cytochemistry and X-ray microanalysis revealed the accumulation of
      calcium in the tubular sER and in some of the empty vacuoles. These results
      suggest important roles for the calcium-containing tubular sER in the regulation
      of the intracellular concentration of calcium during formation of the blastopore,
      as well as a role for empty vacuoles in the dissolution and consumption of lipid
      droplets during early gastrulation.

PMID- 7645764
TI  - Action of testosterone on the estradiol-induced feminization of the male chick
      embryo.
AB  - The early treatment of male chick embryos with estradiol induces the feminization
      of their sex tract, i.e. both their gonads and mullerian tract exhibit female
      features. The additional treatment of estrogenized male embryos with testosterone
      propionate antagonizes the effects of estradiol on both gonads and mullerian
      ducts. Our data give further support to the view that testosterone and estrogens
      act respectively as agonist and antagonist modulators of the secretion of the
      anti-mullerian hormone.

PMID- 7645765
TI  - [Comparative assessment of temperature of the myocardium during its protection by
      2 methods in aortocoronary bypass].
AB  - Eighty-eight patients operated on for coronary heart disease were examined.
      Continuous irrigation of pericardial cavity with circulating cold solution in
      combination with antegrade cardioplegia was used in 53 patients, antegrade
      cardioplegia with external cooling of the heart by icy mass in the rest 35.
      Intensive external cooling provided a stable temperature of the myocardium during
      clamping of the aorta.

PMID- 7645766
TI  - [Early cessation of artificial ventilation of the lungs (extubation of the
      trachea in the operating room) in patients undergoing surgery with artificial
      circulation].
AB  - Forty-nine patients operated on the open heart under combined total anesthesia
      with nitrogen oxide, enflurane or isoflurane and propofol (group 1) and 22 ones
      anesthesized with high fentanyl doses (group 2) were examined. To group 1
      patients fentanyl and pancuronium bromide were injected only in the preperfusion
      period of the operation. Early extubation was carried out in 44 (90%) group 1
      patients. The duration of postoperative artificial ventilation of the lungs was
      102 +/- 15 min in group 1 and 16 +/- 1 h in group 2. No grave postoperative
      complications or early mortality were recorded. In the morning of the first
      postoperative 24 h 7% of group 1 patients and 41% of group 2 ones were
      administered inotropic therapy (p < 0.05). Duration of stay in resuscitation ward
      was 0.96 +/- 0.05 days in group 1 and 2.04 +/- 0.09 days in group 2 (p < 0.01).
      The authors come to a conclusion on the desirability of early extubation after
      open-heart surgery. Indications for and contraindications against early
      extubation are discussed.

PMID- 7645767
TI  - [Pathophysiological aspects of the development of circulatory hypoxia in
      artificial circulation].
AB  - Metabolic status of 650 patients operated on under artificial circulation for
      various cardiac diseases was studied. Circulatory hypoxia was found to underlie
      all metabolic disorders in artificial circulation which manifest by loss of
      buffer bases and lactate accumulation. Development of circulatory hypoxia in
      artificial circulation is caused by inadequate oxygen supply to tissues due to
      initially present disorders of the peripheral bloodstream which augment during
      perfusion by circulation centralization and due to changes of blood rheology,
      particularly so in increase of hypothermia and prolongation of perfusion. Lactate
      concentration during artificial circulation is an objective criterion of tissue
      hypoxia which sufficiently well correlates with development of heart failure in
      the early postperfusion period. When correcting circulatory hypoxia during
      artificial circulation the anesthesiologist and perfusiologist should aim at
      changing the vascular tone towards an increase of the peripheral bloodflow. This
      is particularly important during prolonged hypothermic perfusions in patients
      with initially low reserve potential of the myocardium.

PMID- 7645769
TI  - [Normal-temperature artificial circulation. Warm blood cardioplegia].

PMID- 7645768
TI  - [Intraoperative assessment of the effects of nitroglycerin on myocardial
      contraction in patients with ischemic heart disease during aortocoronary bypass].

PMID- 7645770
TI  - [Anesthesia, changes in hemodynamics and metabolism in resection of abdominal
      aortic aneurysms].
AB  - Changes in hemodynamics and some metabolic parameters were studied in 78 patients
      during anesthesia for resection of the abdominal aorta aneurysms. The steps of
      the operation associated with the most profound hemodynamic changes were
      distinguished and measures aimed at stabilization of hemodynamics, blood volume,
      and electrolyte balance considered. No appreciable changes in the hemodynamics or
      depression of the myocardium were observed at stages of anesthesia and operation.
      A correlation was traced between pressure changes in the pulmonary artery and
      central venous pressure. The suggested method of anesthesia and infusion therapy
      strategy are conducive to stabilization of the hemodynamics in the course of the
      whole operation, to maintenance of normal volume of circulating blood and
      adequate diuresis. Monitoring of central venous pressure is sufficient to control
      infusion therapy and hemodynamics.

PMID- 7645771
TI  - [Maintenance of gas exchange in surgery of the trachea and bronchi].

PMID- 7645772
TI  - [State of the pulmonary surfactant system in relation to thoracic surgery and
      anesthesia].

PMID- 7645773
TI  - [Hemodynamic effects calcium channel blocker isradipine (lomir) in patients with
      arterial hypertension during and after aortocoronary bypass surgery. I and II].

PMID- 7645774
TI  - [Bronchial blood circulation from the viewpoint of the anesthesiologist
      resuscitator].

PMID- 7645775
TI  - [Anesthesiological management of laparoscopic interventions: the problem of
      pneumoperitoneum].

PMID- 7645776
TI  - [Possibilities and prospects of regional anesthesia in the current
      anesthesiological practice].
AB  - Presents a modern concept of conduction blocking, permitting revision of
      indication for it. Blocking is regarded as the basic component of present-day
      anesthesiologic care responsible for analgesia and regional muscle relaxation.
      Use of objective methods of verification of the elements of nervous formations
      improves the efficacy of and extends the range of indications for regional
      blocking solves the problem of regulation, and rational combination of this
      modality with selectively acting drugs provides the optimal realization of
      balanced anesthesia.

PMID- 7645777
TI  - [Choice of anesthesia in geriatric patients in lower limb surgery].
AB  - Three variants of regional anesthesia were used in 162 patients operated on the
      lower limbs. A combination of the inguinal approach after Winnie for the blocking
      of the lumbar plexus and sciatic nerve provided a reliable analgesia in
      operations performed below the middle third of the femur. In interventions on the
      upper third of the femur and the hip joint segmentary conduction blocking
      (epidural or spinal anesthesia) should be preferred in geriatric patients,
      because it is impossible to block the branches of the obturator, sciatic, upper
      and lower gluteal nerves innervating the hip joint by Winnie's technique, an
      anatomical obstacle (fascial node) preventing the procedure, as was shown by
      anatomical experiments with 28 corpses.

PMID- 7645778
TI  - [Adequacy of amputation analgesia as a factor preventing the triggering of pain
      memory in the genesis of phantom pain syndrome].
AB  - Examinations of 72 patients with a history of amputation of the lower limb showed
      that preamputation pain may be transformed into phantom pain via "pain memory"
      mechanisms. This fact is confirmed by similarity of the verbal structure of
      preamputation pain and phantom pain syndrome, which are particularly expressed in
      the patients operated on under total anesthesia. At the same time, the share of
      patients considering phantom pain identical to preamputation pain is much lower
      among those operated on under prolonged perioperative epidural anesthesia, and no
      "pain memory" phenomena are observed in this group 6 months after surgery.
      Prolonged epidural anesthesia provides a pain-free period before surgery by
      disrupting the time relationship between nociceptive impulsation entry in the CNS
      structures and amputation, thus preventing fixation of 'pain experience' survived
      in the memory. The adequacy of intraoperative analgesia attained by prolonged
      epidural anesthesia plays the crucial role in prevention of realization of the
      "pain memory" effect.

PMID- 7645779
TI  - [Combined spinal-epidural anesthesia].

PMID- 7645780
TI  - [Personal computer-based computer monitoring system of the anesthesiologist (2
      year experience in development and use)].
AB  - Creation of computer monitoring systems (CMS) for operating rooms is one of the
      most important spheres of personal computer employment in anesthesiology. The
      authors developed a PC RS/AT-based CMS and effectively used it for more than 2
      years. This system permits comprehensive monitoring in cardiosurgical operations
      by real time processing the values of arterial and central venous pressure,
      pressure in the pulmonary artery, bioelectrical activity of the brain, and two
      temperature values. Use of this CMS helped appreciably improve patients' safety
      during surgery. The possibility to assess brain function by computer monitoring
      the EEF simultaneously with central hemodynamics and body temperature permit the
      anesthesiologist to objectively assess the depth of anesthesia and to diagnose
      cerebral hypoxia. Automated anesthesiological chart issued by the CMS after
      surgery reliably reflects the patient's status and the measures taken by the
      anesthesiologist.

PMID- 7645781
TI  - [Capnomac Ultima: a present-day device for monitoring artificial respiration and
      pulmonary gas exchange].

PMID- 7645782
TI  - [Practical steps in the solution of the problem of patient's safety during
      anesthesia].

PMID- 7645783
TI  - [Myocardial protection from ischemic and reperfusion injuries in reconstructive
      heart surgery].
AB  - Methods of myocardial protection from ischemic and reperfusion injuries in
      various operations on the open heart were compared. The study demonstrated the
      advantages of combined antegrade-retrograde delivery of cardioplegic solution
      during ischemia in aortocoronary shunting and correction of valvular defects. The
      method of myocardial protection from reperfusion injury by perfusing the heart
      with blood solution of a special composition before removing the clamp from the
      aorta (controlled reperfusion) proved to be effective, which was confirmed by
      clinical and biochemical data presented in this paper. Hence, our findings
      confirmed that the optimal protection of the myocardium can be attained by
      combined cold crystalloid cardioplegia together with controlled reperfusion of
      the myocardium.

PMID- 7645784
TI  - [Use of laryngeal mask in a female patient with expected difficult intubation,
      polyvalent allergy and high grade myopia].
AB  - Use of laryngeal mask in combination with gastric intubation permitted anesthesia
      for laparoscopic cholecystectomy in a female patient with disseminated
      osteochondrosis of the spine, expected difficult intubation, manifest polyvalent
      allergy, neurocirculatory dystonia of the hypertensive type, and high myopia. The
      risk of anesthesia was higher than surgical risk because of manifest concomitant
      diseases and aggravated anesthesiologic anamnesis. The operation was effective,
      anesthesia involved no complications, hemodynamics and gas exchange were stable,
      the patient awakened on the operation table and after recovery of adequate
      spontaneous respiration and muscular tone was transferred to resuscitation ward.

PMID- 7645785
TI  - [Several aspects of pathogenesis and treatment of multiple organ failure].

PMID- 7645786
TI  - [Dynamics of the content of the pulmonary extravascular fluid during
      extracorporeal detoxication in critical state patients].
AB  - Time course of the content of interstitial, cellular, and total fluid in the
      lungs, of plasma osmolality and sodium concentration was studied in 20 patients
      with acute renal failure after repair surgery on the heart, thoracic and
      abdominal organs. Water balance of the lungs was studied by dissolution of
      electroimpedance indicators before and after removal of 2000-2500 ml of
      ultrafiltrate. Ultrafiltration of the blood in the course of hemodialysis (group
      1) did not lead to a reliable reduction of the volume of intravascular fluid,
      whereas in group 2 a reliable reduction of the volume of interstitial fluid of
      the lungs by 34% and of the total liquid volume of the lungs by 29% occurred in
      the course of hemofiltration.

PMID- 7645787
TI  - [Acupuncture analgesia and analgesic transcutaneous electroneurostimulation in
      the early postoperative period].
AB  - Efficacies of two methods of nondrug analgesia: acupuncture (1000 cases) and
      antipain transcutaneous electroneurostimulation (91 cases), as well as of
      narcotic analgesics omnopon and promedol (229 cases) were compared in the
      immediate and early postoperative period. In 229 cases acupuncture was used for
      the treatment of other functional complications of the postoperative period. The
      efficacies of the methods in question were assessed by formalized verbal
      estimation scales. Narcotic analgesics provided adequate analgesia in 75 to 79%
      of patients, electrostimulation in 61 to 64%, acupuncture in 50% of patients.
      Acupuncture, though less effective than narcotic analgesics, helped arrest or
      noticeably alleviate the severity of such postoperative complications as reflex
      retention of the urine, impairment of hte drainage function of the bronchi,
      intestinal paresis, bronchial asthma, vomiting, nausea, pain or itching in the
      stoma, chill, hyperthermia in 43 to 81% of cases. The authors come to a
      conclusion on the desirability of an integrative approach (combined use of drugs
      and nondrug methods of analgesia) in the management of postoperative pain.

PMID- 7645788
TI  - [Evaluation of the effectiveness of transcutaneous electroneuroanalgesia in
      phantom pain syndrome].
AB  - Transcutaneous electroneurostimulation carried out in 24 patients with phantom
      pain syndrome completely relieved pain in only 25% of patients. A possible cause
      of poor efficacy of this method is depletion of the endorphin antinociceptive
      mechanisms. EEG findings indicated a possibility of objectively controlling the
      course of analgesia. Specific EEG signs of phantom pain syndrome were
      distinguished: polymorphism of EEG fluctuations, high-frequency rapid or slow
      electrical activity of the brain, and paroxysmal activity. Normalization of EEG,
      i.e. appearance of manifest alpha-rhythm, reduction of the intensities of slow
      wave and rapid activities with the relevant spectral changes, are signs of a
      positive effect of the analgesic method used, as exemplified by transcutaneous
      electroneurostimulation.

PMID- 7645789
TI  - The safety and efficacy of outpatient midazolam intravenous sedation for oral
      surgery with and without fentanyl.
AB  - This study examined midazolam and midazolam plus fentanyl in a placebo
      controlled, double-blind clinical trial. It tested the hypothesis that combined
      drug therapy results in significantly poorer safety but no difference in efficacy
      compared to the single drug approach. Subjects were among 207 mildly anxious
      young adults having their third molars removed. Fentanyl had a significant
      depressant effect on respiration. Fifty of 79 (63%) subjects who received a
      midazolam-fentanyl combination became apneic, while only two of 78 (3%) who
      received midazolam alone were apneic (Fisher's Exact Test, P < 0.001). Two
      subjects (2.5%) in the combination group and none in the midazolam alone group
      had oxygen saturations drop below 90%. About twice as many subjects in the
      combination group had end-tidal carbon dioxide (EtCO2) levels greater than 25%
      above baseline. While these results are consistent with those for apnea,
      contingency analyses of the oxygen saturation and EtCO2 results were not
      statistically significant. Subjects in the combination group were more than four
      times as likely to have excellent versus good, fair, or poor sedation at a given
      level of intraoperative pain, and behavioral (movement and verbalization) but not
      cognitive measures of anxiety were attenuated.

PMID- 7645790
TI  - Safety and effectiveness of intranasal administration of sedative medications
      (ketamine, midazolam, or sufentanil) for urgent brief pediatric dental
      procedures.
AB  - Thirty children presenting to the dental clinic of a pediatric hospital who
      required brief but urgent dental care, and who could not be satisfactorily
      examined or treated, were administered one of three medications--ketamine
      (Ketalar), 3 mg/kg; midazolam (Versed), 0.4 mg/kg; or sufentanil (Sufenta), 1.5
      or 1.0 micrograms/kg--intranasally in a randomized, double-blinded protocol. The
      patients were brought to the day surgery area following appropriate fasting and
      administered one of the medications diluted in a dose of 0.1 mL/kg normal saline
      while sitting in a nurse's arms. Cardiorespiratory monitors were applied when
      tolerated, and the child was placed on the operating room table. Each child was
      injected locally with up to one dental cartridge of 2% lidocaine with 1:100,000
      epinephrine before dental extractions. A sedation score was recorded using a
      scale where 1 = hysterical/untreatable, 5 = ideal sedation, and 10 = obtunded and
      desaturated, requiring airway management assistance. Midazolam administration
      resulted in acceptable sedation (mean score: 4) with no desaturations below 90%
      as measured by pulse oximetry and a mean recovery room observation time of only 3
      +/- 2 min (+/- SD). Ketamine also had a mean sedation score of 4 and a short
      recovery period (7 +/- 7 min); however, two children experienced brief
      desaturations. Sufentanil at 1.5 micrograms/kg was noted to produce much more
      heavily sedated children (mean score 7), with a high incidence of significant
      oximetry desaturation (80%) and prolonged recovery room duration (58 +/- 40 min).
      Use of 1.0 microgram/kg sufentanil resulted in no desaturations, less sedation
      (mean score 4), and a brief recovery time (7 +/- 13 min).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7645791
TI  - Evaluation of a clinical recovery score after general anesthesia.
AB  - A clinical recovery score (CRS) assessing recovery after general anesthesia was
      compared with the Digit-Symbol Substitution Test (DSST), Trieger Test (TT), a
      patient-completed visual analogue scale for alertness (VAS), and an independent
      observer's evaluation of recovery. The CRS included ratings of the following
      parameters: activity, respiration, circulation, consciousness, ambulation, color,
      and nausea and vomiting. Forty patients requiring the removal of three or four
      third molars participated in the study. All patients received the same general
      anesthetic technique. Each patient was evaluated by the five methods
      preoperatively, on admission to the recovery room, and at 15-min intervals until
      discharge. The four recovery tests (CRS, DSST, TT, VAS) were evaluated using chi
      2 analysis to determine if there was any overall difference among the tests using
      the observer's determination of home readiness as the standard for discharge. The
      CRS was significantly more in agreement with the observer's determination than
      were the paper and pencil tests. The recovery tests were also evaluated with
      regard to instances of early dismissal or prolonged retention of the patient,
      again using the observer's determination as the "gold standard." The CRS was the
      only recovery test devoid of early dismissals. We conclude that the CRS provides
      a valid, simple measure of recovery that can be readily used in offices providing
      outpatient anesthesia and in studies measuring clinical recovery from anesthesia
      or sedation.

PMID- 7645793
TI  - ASDA specialty application.

PMID- 7645794
TI  - Electronic dental anesthesia.

PMID- 7645792
TI  - Long-term effects on dental care behavior and dental health after treatments for
      dental fear.
AB  - Three different treatments for dental fear were tested in a long-term perspective
      study. Twenty-nine patients with severe dental anxiety and avoidance behavior
      were assigned to Behavioral Therapy (BT, n = 12), PRemedication with
      bensodiazepine (PR, n = 8) or dental treatment under General Anesthesia (GA, n =
      9). Ten years after initial treatment the patients were reexamined. Changes in
      dental anxiety and dental care attendance were reported. Patients' dental health
      status was assessed by radiographic survey. Regular dental attendance was
      reported by 19 patients (65.5%), with a significantly better result for the BT
      group (91.6%) compared to the GA group (33.3%). Reported level of dental anxiety,
      as measured by the Dental Anxiety Scale, revealed a significant reduction during
      the 10-yr period except among GA patients and those reporting irregular dental
      attendance behavior. A rise in mood as assessed by the Mood Adjective Checklist
      was revealed in the total group, with a better effect in the BT and PR groups as
      well as in patients who reported regular dental attendance. A substantial general
      improvement in oral health was seen during the 10-yr period, especially among
      patients receiving regular dental care. Thus, for a majority of patients in this
      study, directed treatment for dental anxiety and avoidance behavior made it
      possible to maintain regular dental care behavior during a 10-yr period.

PMID- 7645795
TI  - More than 25,000 RNs march on Washington, issuing a wake-up call to consumers and
      lawmakers.

PMID- 7645796
TI  - Teamwork ensured march's success.

PMID- 7645797
TI  - State Medicaid waivers: issues for nursing.

PMID- 7645798
TI  - Debate on institutional licensure resurfaces.

PMID- 7645799
TI  - A united nursing language: the missing link in establishing nursing-sensitive
      patient outcomes.

PMID- 7645800
TI  - Continuing education program: integrating an understanding of sleep knowledge
      into your practice. Part 5. Sleep problems in older adults (continuing education
      credit).

PMID- 7645801
TI  - Continuing education program: integrating an understanding of sleep knowledge
      into your practice. Part 6. Sleep in infants, young children and adolescents
      (continuing education credit).

PMID- 7645802
TI  - ANA creates new on-line computer network for nurses.

PMID- 7645803
TI  - The critical care of those with AIDS.

PMID- 7645804
TI  - Grants are foundation of ANA's work on HIV/AIDS issues.

PMID- 7645806
TI  - A diverse march with a unified message.

PMID- 7645805
TI  - Anti-regulatory fast track in Congress could derail RN's workplace protections.

PMID- 7645808
TI  - ANA initiative to help nurses 'survive' restructuring.

PMID- 7645807
TI  - RNs need the true leadership of ANA and the SNAs.

PMID- 7645809
TI  - From Boys Town to Oliver Twist. Separating fact from fiction in welfare reform
      and out-of-home placement of children and youth.
AB  - Recent debate following the suggestion to place children of "welfare mothers" in
      "orphanages" illustrates the need to evaluate the relative goodness of
      residential care and to examine many of the basic assumptions underlying current
      welfare reform proposals. Nearly half a million children and youth are currently
      in government-funded out-of-home care in the United States. As custodians of this
      challenging population, child and youth care workers are neither parents nor
      therapists, but appear to perform both of these roles as "therapeutic parents."
      Two comprehensive and mature literatures--common factors of therapist efficacy
      and parental correlates of offspring psychopathology--provide theoretical and
      empirical support for this model of child and youth care. Current welfare reform
      proposals are evaluated in the context of the therapeutic parent model;
      assumptions about welfare mothers are also examined.

PMID- 7645810
TI  - T-cell receptor V-region usage and antigen specificity. The cytochrome c model
      system.
AB  - Investigations of the I-Ek-restricted, cytochrome c-specific T-cell response in
      mice show that both T-cell receptor V alpha and V beta CDR3 residues and the use
      of particular V alpha s and V beta s are necessary for recognition. Data strongly
      suggest that specific CDR3 residues are important in contacting the peptide.
      Other experiments indicate that the requirement for V alpha:V beta conservation
      is not the result of strong TCR-->MHC interactions, as no correlation was found
      between V beta usage and changes in the alpha-helixes of the I-Ek molecule. It is
      also apparent that changes in V alpha or V beta usage could be elicited by
      changes in the side chain size of single amino acids of the antigenic peptides,
      suggesting that V alpha or V beta conservation is important for peptide
      recognition, either directly or indirectly. We also show that we can follow the
      cytochrome c response in vivo even in nontransgenic mice, solely by staining with
      anti-V region antibodies as well as mAbs directed at the activation markers CD44
      and L-selectin.

PMID- 7645811
TI  - Analysis of the human T-cell receptor V gamma gene usage by flow cytometry.

PMID- 7645812
TI  - Monoclonal antibodies to human T-cell receptor variable beta regions.

PMID- 7645813
TI  - Bacterial toxin superantigens stimulate all members of susceptible VB gene
      families.

PMID- 7645814
TI  - Evidence for an endogenous superantigen deleting human V beta 2 positive T
      lymphocytes.

PMID- 7645815
TI  - Construction of a superantigen through a structural modification of an inactive
      protein.

PMID- 7645816
TI  - T-cell receptor usage of major histocompatibility complex class I restricted
      peptide-specific T-lymphocytes.

PMID- 7645817
TI  - Generation of a panel of transfected murine cells expressing human V beta.
      Application to the study of fine specificities of superantigens.

PMID- 7645818
TI  - Human T-cell receptor gene nomenclature.

PMID- 7645819
TI  - Expansions of V alpha 12 CD8+ T-cells in rheumatoid arthritis.

PMID- 7645820
TI  - V-genes of T-cell receptors in rheumatoid arthritis.

PMID- 7645821
TI  - T-cell receptor use in early rheumatoid arthritis.

PMID- 7645822
TI  - T-cell receptor V beta gene utilization in rheumatoid arthritis.

PMID- 7645823
TI  - The role of T-cell receptor beta chain genes in the susceptibility to rheumatoid
      arthritis.

PMID- 7645824
TI  - Analysis of the peripheral blood T-cell receptor repertoire in monozygotic twins
      discordant for rheumatoid arthritis.

PMID- 7645825
TI  - CDR3 length restriction of T-cell receptor beta chains in CD8+ T-cells of
      rheumatoid arthritis patients.

PMID- 7645826
TI  - T-cell receptor gamma/delta usage in rheumatoid arthritis. Persistence of
      oligoclonality in the periphery.

PMID- 7645827
TI  - Unstimulated rheumatoid synovial T-cells have a consistent V beta gene bias when
      compared to peripheral blood T-cells.

PMID- 7645828
TI  - Oligoclonality in the CD8+ T-cell population. Analysis using a multiplex PCR
      assay for CDR3 length.

PMID- 7645829
TI  - Analysis of synovial fluid T-cell repertoires by CDR3 size spectratyping reveals
      possible antigen and superantigen stimulation.

PMID- 7645830
TI  - Characterization of oligoclonal synovial T-cells in rheumatoid arthritis.

PMID- 7645831
TI  - Oligoclonal T-receptor (V beta) use in the response to connective tissue antigens
      by synovial fluid T-cells from rheumatoid arthritis patients.

PMID- 7645832
TI  - Use of T-cell receptor V genes in synovial membrane in rheumatoid arthritis.

PMID- 7645833
TI  - T-cell receptor V beta gene usage in rheumatoid synovial follicles.

PMID- 7645834
TI  - Evidence for selective in vivo expansion of synovial tissue-infiltrating
      CD4+CD45RO+ T-lymphocytes on the basis of CDR3 diversity.

PMID- 7645835
TI  - High frequencies of identical T-cell clonotypes accumulating in different areas
      of synovial lesions of rheumatoid arthritis patients.

PMID- 7645836
TI  - V beta 17 T-cell receptor peptide vaccine. Results of a phase I dose-finding
      study in patients with rheumatoid arthritis.

PMID- 7645837
TI  - Comparison of epitope specificity and T-cell receptor usage in response to type
      II collagen immunization between H-2q and H-2r mice.

PMID- 7645838
TI  - Effect of constrained T-cell receptor repertoires on collagen-induced arthritis
      in T-cell receptor V beta transgenic and congenic mice.

PMID- 7645839
TI  - Limited heterogeneity in T-cell receptor V beta chain gene expression in
      arthritic joints of BUB/BnJ (H-2q) mice--a T-cell receptor V beta a strain.
AB  - We have earlier shown that T-cells in arthritic joints and LNs of B10.Q mice (H
      2q, TCR V beta b) use a restricted number of TCR V beta chain genes (V beta 6, 8,
      9). In the present study, we have investigated the TCR V beta chain gene
      expression in arthritic joints and LN of BUB/BnJ mice (H-2q, TCR V beta a). Mice
      were immunized with [table: see text] chicken type-II collagen, and arthritic
      joints and draining LNs were removed at the onset of arthritis and the TCR V beta
      chain gene expression was studied by PCR. A restricted usage of TCR V beta was
      observed in both the tissues. A dominant usage of TCR V beta 4, 7, and 15 was
      found in the LNs while TCR V beta 3 and 10 were predominantly expressed in
      arthritic joints in the majority of the arthritic mice (5/7). Our results
      indicate that (a) in H-2q mice with CIA there is a restricted usage of TCR V beta
      chain genes regardless of the TCR V beta genotype; and (b) in the absence of TCR
      V beta 8 and 9, TCR V beta 3 and 10 are predominantly used by joint-infiltrating
      T-cells.

PMID- 7645840
TI  - Restricted T-cell receptor usage in DA rats during early collagen-induced
      arthritis.

PMID- 7645841
TI  - Anti-T-cell receptor peptide specific T-cells and adjuvant arthritis.

PMID- 7645842
TI  - T-cell receptor use in rheumatoid arthritis.

PMID- 7645843
TI  - T-cell receptor genes. Germline polymorphisms and genetic susceptibility to
      demyelinating diseases.

PMID- 7645844
TI  - The influence of genetics, environment, and disease state on the human T-cell
      receptor repertoire.

PMID- 7645845
TI  - The T-cell receptor in multiple sclerosis.

PMID- 7645846
TI  - Characterization of T-cell receptor V beta usage in the brain of a subject with
      multiple sclerosis.

PMID- 7645847
TI  - DNA sequence and polymorphism analysis of a region of the T-cell receptor beta
      locus thought to contain a susceptibility gene for multiple sclerosis.

PMID- 7645848
TI  - Clonal dominance of CD8+ T-cell in multiple sclerosis.

PMID- 7645849
TI  - T-cell receptor gene expression in autoimmune thyroid disease: some observations
      and possible mechanisms.

PMID- 7645851
TI  - T-cell receptor use in sarcoidosis.

PMID- 7645850
TI  - Human autoreactive T-cell clones show flexibility in recognizing overlapping
      microepitopes, but inflexibility in T-cell receptor usage.

PMID- 7645852
TI  - Disease-specific structural motifs of alpha beta T-cell receptors expressed by
      salivary gland T-cells in sicca syndrome.

PMID- 7645853
TI  - CD8+ T-cells in psoriatic lesions preferentially use T-cell receptors V beta 3
      and/or V beta 13.1 genes.
AB  - Restricted T-cell receptor V beta gene use in animal models of autoimmune disease
      has led to the development of strategies to treat autoimmune disease by targeting
      the T-cell receptors of the pathogenic T-cells. Restricted T-cell receptor gene
      use has been noted in human autoimmune diseases such as rheumatoid arthritis and
      multiple sclerosis. We report here the finding of restricted T-cell receptor gene
      use in psoriasis vulgaris, as well. Our results show an elevated skin (over PBL)
      expression of V beta 3 and/or V beta 13.1 messages in the CD8+ T-cells in a
      majority of patients studied. CDR3 sequence analysis on these two V beta s from
      the skin demonstrated monoclonality or marked oligoclonality. A second biopsy
      performed 3.5 to 8 months later in four patients, at the same or different
      lesions, again revealed an elevated V beta 3 and/or V beta 13.1 expression and
      clonality. Moreover, in three of the four patients, the same TcR V beta CDR3
      rearrangement was found in both biopsies, although there was no V beta CDR3
      homology noted between patients. In two patients in which V beta 3 and/or V beta
      13.1 was not elevated in the CD8+ T-cell population, an increase in V beta 17
      gene use and clonality was found. The persistence of V beta 3- and/or V beta 13.1
      bearing CD8+ T-cells in lesions that did not undergo resolution suggests their
      role as effector cells rather than as regulatory cells. The effector function of
      these CD8+ T-cells is further supported by the clonality of TcR V beta sequence
      data, which indicates they are recruited and expanded in situ. The V beta s
      identified in this study are candidate targets for selective immunotherapeutic
      intervention in psoriasis.

PMID- 7645854
TI  - Oligoclonal expansion of V delta 1+ gamma/delta T-cells in systemic sclerosis
      patients.
AB  - Systemic sclerosis (SSc) is a multisystem disease characterized by T-cell
      infiltration of involved tissues, fibrosis, and small vessel vasculopathy. Using
      flow cytometric analyses, we found an increased percentage of gamma/delta T-cells
      expressing the T-cell antigen receptor variable (V) delta 1 gene segment in the
      peripheral blood and bronchoalveolar lavage fluid of patients with SSc. To
      estimate clonality of these V delta 1+ T-cells, the diversity of V delta 1
      junctional regions (V-Diversity-Joining gene segments) was examined using a
      reverse transcriptase-polymerase chain reaction to amplify T-cell antigen
      receptor delta chain transcripts isolated from peripheral blood mononuclear
      cells, lung, esophagus, stomach, or skin of patients and controls. Limited
      diversity of V delta 1-J delta junctional regions in SSc patients was
      demonstrated by the finding of greater restriction in the nucleotide lengths of
      junctional region cDNAs in individual SSc patients than in controls. Sequence
      analyses confirmed that V delta 1-J delta junctional regions from the blood of
      SSc patients had less diversity than those from controls, in that a significantly
      higher proportion of sequences were repeated in patients (54.4% vs. 19.4% in
      controls). Evidence for selection of the V delta 1+ T-cells in tissues of
      individual SSc patients came from the findings that the same V delta 1-J delta
      junctional sequences could be isolated from the same tissue over time and that
      identical V delta 1-J delta junctional sequences could be isolated from multiple
      tissues. These data suggest that expansion of V delta 1+ gamma/delta T cells may
      be antigen driven in SSc patients.

PMID- 7645855
TI  - Enhanced V beta 7 gene usage by intestinal T-lymphocytes in nondiseased human gut
      moieties.

PMID- 7645856
TI  - Phenotype and cytokine profile of intraepithelial lymphocytes in human small and
      large intestine.

PMID- 7645857
TI  - T-cell receptor V gamma and V delta gene transcription in celiac disease gut.

PMID- 7645858
TI  - V beta-specific changes in the T-cell receptor repertoire of lamina propria
      lymphocytes in Crohn's disease.

PMID- 7645859
TI  - Human gamma delta T-cells in the epithelium of the gut and in the inflamed
      synovial tissue preferentially express the V gamma 8 T-cell receptor chain.

PMID- 7645860
TI  - The alpha beta T-cell receptor repertoire in idiopathic inflammatory myopathies:
      distinct patterns of gene expression by muscle-infiltrating lymphocytes in
      different clinical and serologic groups.

PMID- 7645861
TI  - T-cell receptor-CDR3 sequences of polymyositis muscle-infiltrating T-lymphocytes
      indicate a conventional antigen as target.

PMID- 7645862
TI  - T-cell infiltration in polymyositis is characterized by coexpression of cytotoxic
      and T-cell-activating cytokine transcripts.

PMID- 7645863
TI  - Analysis of the T-cell receptor beta chain repertoire expressed in endogenous
      posterior uveitis.

PMID- 7645864
TI  - T-cell receptors in scleroderma skin. The effect of photopheresis.

PMID- 7645865
TI  - DsDNA-specific T-cell lines in systemic lupus erythematosus patients: data
      suggesting their oligoclonality.

PMID- 7645867
TI  - Oligoclonal T-cell repertoire and graft-versus-host disease after allogeneic bone
      marrow transplantation.

PMID- 7645866
TI  - Analysis of the V beta T-cell receptor repertoire in autologous graft-versus-host
      disease.

PMID- 7645868
TI  - T-cell receptor expression in the thymus from patients with myasthenia gravis.

PMID- 7645869
TI  - T-cell receptor repertoire in pulmonary sarcoidosis.

PMID- 7645870
TI  - Use of a polymorphic dinucleotide repeat DNA marker in a T-cell receptor V beta
      gene to identify a distinct subset of pauciarticular-onset juvenile rheumatoid
      arthritis patients.

PMID- 7645871
TI  - V beta-specific activation of T-cells by the HIV glycoprotein gp160.

PMID- 7645872
TI  - T-cell receptor V beta gene usage in experimental autoimmune thyroiditis.

PMID- 7645873
TI  - T-cell receptor use in organ-specific human autoimmune diseases other than
      rheumatoid arthritis and multiple sclerosis. Summary and overview.

PMID- 7645874
TI  - T-cell repertoires in health and disease.

PMID- 7645875
TI  - Dual receptor T-cells. Implications for alloreactivity and autoimmunity.
AB  - Using monoclonal antibodies to human V alpha, we have estimated that up to one
      third of mature T-cells express two V alpha chains as part of two functional and
      independent T-cell receptors. Cells belonging to this dual TCR subset may be
      specific for a broader range of antigens than cells with a single receptor. We
      discuss the possibility that dual receptor T-cells may be involved in
      alloreactivity and autoimmunity.

PMID- 7645876
TI  - Environmental and genetic factors shape the human T-cell receptor repertoire.
AB  - Both environmental and genetic factors combine to shape the TCR repertoire as
      measured by V gene usage. These factors may result in dramatic shifts in normal
      subjects, which cannot be discounted when studies are performed in patients with
      disease. Future studies need to explore further examples of genetic and
      environmental factors that shape the TCR repertoire to understand the full extent
      of variation in a normal population and the mechanisms involved. Some of these
      mechanisms may also apply to TCRG, TCRD, and immunoglobulin loci. Certainly
      variations in the efficiency of V(D)J rearrangement could affect any rearranging
      multigene locus. Eventually such studies will lead to better designed clinical
      studies of the repertoire in disease, through the selection of control
      populations matched for environmental exposure and genetic background. In this
      respect, family studies will be most useful.

PMID- 7645877
TI  - Forces molding circulating T-cell repertoires. Thymic events studied by
      recombination analysis.

PMID- 7645878
TI  - Analysis of T-cell receptor V beta expression among V alpha subsets. Evidence for
      tight regulation of the combinatorial diversity.

PMID- 7645879
TI  - Evidence for preferential recombination events in normal human T-cell
      repertoires.

PMID- 7645880
TI  - Frequency of human V beta 3+ cells correlates with polymorphism in recombination
      signal sequences.

PMID- 7645881
TI  - Preferential expression of the human V beta 7.1 gene segment on CD8+ peripheral
      blood lymphocytes.

PMID- 7645882
TI  - Variability in CD8+ T-cell oligoclonality patterns in monozygotic twins.

PMID- 7645883
TI  - Improvements in repertoire analysis by CDR3 size spectratyping. Bifamily PCR.

PMID- 7645884
TI  - [Deafness and auto-immunity: what is the role of antiphospholipid syndrome?
      Apropos of 35 cases].
AB  - Currently, the importance of autoimmune phenomenon in the genesis of inner ear
      disease is difficult to evaluate because the clinical and biological criteria of
      autoimmune deafness has not yet been well defined. Among patients with
      sensorineural hearing loss, is it possible to define a group presenting clinical
      and biological findings suggesting autoimmune disease? What are the most
      sensitive and selective biological tests for autoimmune disease of the inner ear?
      Do patients with autoimmune deafness present a particular clinical, genetic and
      for biological profile? In order to answer these questions, we retrospectively
      studied 35 patients followed in our service from June 1990 to August, 1992 for
      sensorineural hearing loss of an unknown origin. All patients had had a complete
      biological work-up including examinations which would detect inflammation
      (erythrocyte sedimentation rate immunoglobulin IgG, IgA, IgM assays, protein
      electrophonesis) or dysimmunity (circulating immune complexes, marked depression
      of serum complement levels the presence of antinuclear antiorgan antibodies, or
      anticardiolipid and type II anticollagen antibodies). HLA typing had also been
      done. RESULTS. Only 4 patients had a biological profile suggesting dysimmunity.
      These patients presented no common clinical or genetic characteristic which would
      distinguish them as a separate subgroup. Biologically, anticardiolipid antibodies
      were found in all 4 of these patients and only in these patients. These 4
      patients also had circulating immune complexes and 3 of the 4 patients also had
      elevated levels of IgA and IgM. IN CONCLUSION: including assays for
      antiphospholipid antibodies in the work-up of sensorineural hearing loss could
      reveal an antiphospholipid syndrome affecting the inner ear. Theoretically, the
      use of anticoagulants and agents decreasing platelet aggregation could provide
      effective treatment.

PMID- 7645885
TI  - [Cholesteatoma in children. Apropos of 104 cases].
AB  - Between 1988 and 1993, 94 children from 3 to 15 years of age underwent one or
      more surgical procedures for cholesteatoma or epithelization of the middle ear
      space. Ten children had bilateral disease. 94 ears were operated for the first
      time and 10 ears had had previous surgery at other institutions. A total of 204
      procedures were performed: 190 for cholesteatoma and 14 for epithelization of the
      middle ear space. Preoperative audiometry showed a mean air-bone gap of 30
      decibels. 69% of the ears had ossicular osteolysis. The surgical technique was
      decided at the time of surgery. This was most often a canal-wall-up procedure
      which was almost routinely followed by surgical revision (92%). Pearl-like masses
      or recurrent cholesteatoma were frequently found at the second or third operation
      (73%) but most could ultimately be controlled with a canal-wall-up procedure. A
      canal-wall-up down procedure was necessary in 20% of the ears at either the
      second or third operation because of important residual or recurrent
      cholesteatoma. Post-operative audiometry showed a mean air-bone gap of 30
      decibels.

PMID- 7645886
TI  - [Section of the facial nerve. Apropos of 40 cases].
AB  - From January, 1985 through December, 1992, 40 patients were referred to the
      Department of Otoneurology of the Lille University Hospital for traumatic facial
      nerve injury. The injury was located in the intracranial, intratemporal, or
      extracranial segments of the nerve in 19, 15 and 6 patients, respectively. The
      trauma was iatrogenic in 30 patients. It was the result of surgery for a tumor of
      the posterior fossa, of the temporal bone or of the parotid in 19, 2 and 3
      patients, respectively. Nerve injury had occurred during surgery for chronic
      otitis or a parotid fistula in 5 and 1 patients, respectively. Finally, it was
      the result of temporal bone fracture in 7 patients. We used various techniques
      for repair of the nerve. Anastomosis, whether end to end or with an interposition
      graph and with or without rerouting, was accomplished in 17 patients, as often as
      possible during the first month following injury (12/17 patients).
      Hypoglossofacial crossovers were used in 23 patients. Evaluation of the results
      may vary according to the choice and interpretation of an international facial
      nerve grading system. We define 4 categories of results: satisfactory, moderate
      poor and no improvement. The results of anastomosis were best when the repair
      with or without rerouting was undertaken as soon after injury as possible (7
      satisfactory results for 16 patients evaluated). Hypoglossofacial anastomosis
      gave 5 satisfactory results for 17 patients evaluated. Following this operation a
      spastic tendency is frequent and seems more important in patients operated during
      the two months following nerve injury.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7645887
TI  - [Clinical value of interaural time discrimination].
AB  - The interaural time discrimination (ITD) is one of the azimuthal sound location
      cues. In multiple sclerosis subjects, deficits in binaural timing discrimination
      are closely related to abnormalities in brainstem auditory evoked potentials
      (BAEPs). To determine if psychophysical performances could be related to the
      BAEPs in other otoneurological deficits, thresholds of ITD were measured in 168
      patients and the results correlated to the electrophysiological responses to
      clicks. Both tests were normal in 29.8% and abnormal in 42.2% of cases. A
      discrepancy existed in 28.0%: ITD abnormal--BAEPs normal in 23.2%, ITD normal-
      BAEPs abnormal in 4.8%. In conclusion, in cases with normal ITD thresholds, the
      probability of a retrocochlear lesion is low. The test of ITD is helpful when the
      interpretation of the BAEPs is difficult because of desynchronized waves.

PMID- 7645888
TI  - [Auditory evoked potentials by electric stimulation of the cochlea].
AB  - The recording of auditory brain stem potentials evoked by electrical stimulation
      of the cochlea is a part of our assessment protocol before pediatric cochlear
      implantation. It constitutes an objective and reproducible method to estimate the
      stimulability of the auditory system for candidates to cochlear implant. Ten
      children, aged from 3 to 12 years, with deep deafness of the 2nd and 3rd group
      with no response to ABR, undergone electric stimulation of the cochlea. All
      patients were anesthetized and paralyzed. Electric pulses are delivered by a
      cochlear stimulator, through a transtympanic needle electrode, placed in the
      promontory. We record responses on a Medelec "Saphire" computer. One of the main
      problem we try to solve is the stimulus artefact which occurs during the first
      ms. The other one is to be sure that the recorded responses are corresponding to
      the neural activity of the auditory nerve and the brainstem auditory pathway.

PMID- 7645889
TI  - [Surgical treatment of snoring and sleep apnea syndromes. Results apropos of 59
      cases].
AB  - From 1991 to 1993, 59 patients underwent surgical cure for snoring.
      Polysomnography was performed 47 times when history taking and clinical signs
      revealed diurnal and nocturnal manifestations. Sleep apnea was confirmed in 20
      patients with a mean apnea-hypnea index of 34.1. Treatment was based on surgery
      of the velum palatinum in 59% of the cases, the palatine tonsils in 39% and the
      basilingual tonsils in 1 patient. Snoring disappeared in 24 patients (40%) and
      improved for 75% satisfaction in 22 patients (37%).

PMID- 7645891
TI  - [Relapsing polychondritis. Apropos of a case].
AB  - The relapsing polychondritis is a rare autoimmune disease. The pathologist finds
      a fibrous degeneration of the cartilage of the body. A case relapsing
      polychondritis is presented and the disorders of the disease are reviewed. The
      larynx and trachea location is a fact of a poor prognosis.

PMID- 7645890
TI  - [Computerized evaluation of acoustic parameters of voice and speech after partial
      supracricoid laryngectomy with cricohyoidoepiglottopexy].
AB  - Nineteen supracricoid porticol laryngectomy (SCPL) with cricohyoidoepiglottopexy
      (CHEP) speakers and 19 normal adult laryngeal (NAL) male speakers took part in
      this prospective study. Computed analysis of the voice and speech parameters was
      performed using the Computed Speech Lab from Kay Elemectrics. Parameters recorded
      for voice analysis were the average fundamental frequency, the fundamental
      frequency standard deviation, the jitter, the shimmer, the noise to harmonic
      ratio and the degree of voiceless. Parameters recorded for speech analysis were
      the maximum phonation time of the /a/ vowel, the phrase grouping and number of
      words read per minute. Speech and voice parameters statistically differed among
      NAL and SCPL with CHEP speakers. Among SCPL with CHEP speakers, none of the
      following factors (age, cricopharyngeal myotomy, piriform sinus tension,
      associated ipsilateral neck dissection, speech rehabilitation therapy) were
      statistically related to the frequential and durational variables. Jitter of SCPL
      with CHEP speakers was reduced as time elapsed from CHEP completion increased (p
      = .002). Maximum phonation time was reduced if one arytenoid cartilage was
      resected (p = 0.025).

PMID- 7645892
TI  - [Secondary malignant tumors of the parotid area].
AB  - Secondary malignant tumors of the parotid gland are uncommon. They arise from
      primary tumors located in the head and neck or from distant primary tumors. The
      formers are dominated by squamous cell carcinomas and melanomas, the latters by
      kidney and bronchic cancers. Distinction between malignant primary tumors and
      metastasis of other primary tumors to the parotid gland is very important to
      appreciate, because the result of this will change therapeutic procedure and the
      evaluation of prognosis. The rarity of this metastatic site is illustrated by
      this series of 9 cases. These observations raised discussion about the site of
      the primary tumor, the localization in the parenchyma or in the lymph nodes, and
      the histological differential diagnosis.

PMID- 7645893
TI  - [How to evaluate a deglutition disorder in the adult?].

PMID- 7645894
TI  - [Cervical paraganglioma. Results apropos of a series of 33 patients].
AB  - During the period 1971-1993, 33 patients were treated for cervical chemodectomas,
      41 tumors were diagnosed. Seven patients had multicentric tumors. All patients
      expect one with bilateral carotid tumor were treated surgically. A carotid
      resection was performed in 4 patients. Six patients were given radiation therapy:
      five patient after surgery and one treated by irradiation alone. During the
      follow-up period one patient died of bone metastasis 6 years after a partial
      surgery and radiation therapy, and one had local recurrence treated with
      irradiation. The surgical management is the major treatment of these tumors, it
      revealed no postoperative cerebrovascular accident and limited complications
      secondary to unavoidable nerves sacrifice. Radiation therapy is performed only on
      particular cases: surgery contra-indications and nonradical resection.

PMID- 7645895
TI  - [Subtotal laryngectomy with cricohyoidopexy. Carcinologic results and early
      functional follow-up. Apropos of 49 cases].
AB  - Forty-three patients underwent a subtotal laryngectomy with cricohyoidopexy and
      neck dissection. The 5 years overall survival rate was 67%, the actuarial
      survival rate was 75%. The 5-year actuarial local control and nodal control rate
      were namely 89% and 90%. Pronostic factors for survival were tumor size (5-year
      actuarial survival rate for T2a, T2b and T3 were namely 89%, 72%, 48%) and node
      involvement (5 years actuarial survival rate was 85% if N-, and 46% if N+). The
      median duration was 22 days for decanulation, 30 days for removing the feeding
      tube. The median hospital discharge day was 38. Total laryngectomy was performed
      in one case (2.3%) for persistent aspiration. Post operative mortality was 0%.
      The most common complication was aspiration pneumoniae (11.6% of the cases).

PMID- 7645896
TI  - [Role of the basal cochlea in the genesis of evoked acoustic oto-emissions in the
      subject with normal hearing].
AB  - The aim of this study was to determine the role of the basal part of the cochlea
      (8-16 kHz) on the genesis of evoked otoacoustic emissions (EOEs) in normally
      hearing subjects (0.25-8 kHz thresholds below or equal to 20 dBHL). This study
      was realized on 43 subjects. The EOEs were generated by a linear click of 0 dB
      (ILO88 Ref.). The high-frequency (8-16 kHz) audiometric thresholds varied between
      30 and 74 dBHL while conventional audiometric thresholds were below 20 dBHL.
      Correlation studies between EOE amplitude and audiometric thresholds were
      statistically significant only when the high frequency thresholds were
      considered. Those data are a new argument for the hypothesis that EOEs are
      generated by the global cochlear activity.

PMID- 7645897
TI  - [Surgical approach to petroclival meningioma. Value of translabyrinthine approach
      extended to the petrous apex].
AB  - Petro-clival meningiomas are rare tumors. Because of their deep location in the
      posterior fossa, many surgical approaches have been proposed, generally with
      severe post-operative morbidity and mortality. Thirty-six meningiomas of the
      petrous apex (34 posterior surface of petrous bone meningiomas, 2 clivus
      meningiomas) were operated, via a trans petrosal approach, from 1983 to 1993. In
      14 cases, the trans-labyrinthine (TL) approach, extended by drilling the bone
      above the internal auditory canal (IAC) was performed (39%). In 18 cases the TL
      approach was extended in a subtemporal, transtentorial approach (50%). In one
      case (2.5%), after rerouting the facial nerve posteriorly, the TL approach was
      extended anteriorly in a transcochlear approach. The retro-sigmoid approach was
      performed in one case (2.5%). The extended middle fossa approach was performed in
      two cases of clivus meningiomas (5%). Total excision was obtained in 27 cases
      (75%). By using the Laser, quality of resection is increased. Most complications
      and morbidity were encountered with tumors extending towards the cavernous sinus.
      Extended translabyrinthine approach allows total excision in most of cases of
      petro-clival meningiomas. For clivus tumors or tumors invading the cavernous
      sinus, the extended middle fossa approach and subtotal petrosectomy are proposed
      respectively.

PMID- 7645898
TI  - [Results of the treatment of spontaneous widening of tracheo-esophageal punctures
      after laryngeal implant].
AB  - Vocal rehabilitation by tracheosophageal puncture procedure and voice prosthesis
      was employed in a series of 68 patients (64 men and 4 women). The mean age was
      68.4 years and ranged from 39 to 78 years. Enlarging tracheoesophageal fistula
      and leakage occurred in 31 patients. One or several conservative treatments were
      employed in 23 patients. Surgical closure of the tracheoesophageal fistula was
      performed in 5 patients (closure without muscular interposition: 3 patients,
      closure with sternomastoid muscle interposition: 2 patients). Leakage around the
      prosthesis was noted 8 days to 39 months postoperatively (mean: 11 months).
      Successful rates of conservative treatments were as following: prosthesis
      replacement with a small gauge catheter for several days followed by a prosthesis
      replacement: 9/17 (52.9%), replacement of prosthesis: 4/12 (33%), Gax Collagen
      injection: 3/9 (33%), cauterization of the tracheoesophageal tract: 0/1. Surgical
      closure was successful in all cases. Repuncture and prosthesis replacement was
      successful in one patient. Conservative treatment is initially recommended
      including prosthesis replacement with a small gauge catheter for several days and
      followed by a prosthesis replacement. Surgical treatment with muscular
      interposition is recommended in case of failure of conservative treatments.

PMID- 7645899
TI  - [The attic. Anatomoclinical correlation].
AB  - Among the hidden parts of the middle ear, the posterior part of the atrium
      undoubtedly raises the most interest of otologists. The attic is a frequent
      localization of cholesteatoma and retraction pouches. Its anatomy is not well
      known, especially the anterior and internal walls. This anatomic study, based on
      the dissection of 41 petrus bones was designed to determine the anatomic limits
      and describe the "noble structures" of this region in order to "guide" future
      surgical procedures.

PMID- 7645900
TI  - [Minor aplasia of the ear: anatomical findings and results of functional
      surgery].
AB  - We report a retrospective study of 57 cases of minor aplasia of the ear. Each
      case was analyzed according to the clinical presentation, audiometric results and
      preoperative radiography. Intra-operative classification of the malformation was
      obtained in 56 of the 57 cases. The post-operative anatomic and functional
      results were analyzed. Stapedectomy in type II malformations (stapedo-vestibular
      ankylosis) gave the best results but this procedure also carries the highest risk
      for the inner ear. Globally, functional results were good or average in 48% of
      the patients. These results may appear unsatisfactory but must be appreciated in
      light of the fact that half of the patients benefited from the operation
      (particularly in eliminating further use of an external hearing aid).
      Nevertheless, the long-term stability of these audition results is unknown.

PMID- 7645901
TI  - [Laryngocele as an etiology of respiratory distress].
AB  - Laryngocele is usually benign affection of the larynx. But serious forms of
      clinical emergency necessitating tracheotomy are possible. We reported 3 cases.
      New methods of treatment are presented endoscopic resection and laser
      marsupialization.

PMID- 7645902
TI  - [How to do it? Nasopharyngolaryngeal fibroscopy in children].

PMID- 7645903
TI  - Immediate breast reconstruction revisited.
AB  - Immediate breast reconstruction was discussed from the psychological, oncological
      and surgical points of view. It has been found that at present no adverse effects
      of the procedure on the course of breast cancer are known, while immediate timing
      is connected with significant psychological and surgical benefits.

PMID- 7645905
TI  - Outcome of surgical treatment in acute upper limb ischaemia.
AB  - During a 26 years' period, 547 thromboembolectomies were undertaken for acute
      limb ischaemia. The portion of upper limb ischaemia was 17.7% (97/547). The
      annual incidence of surgically treated acute upper limb ischaemia was 1.3
      cases/100,000/year during the last 15 years of study period. There were 91
      patients, 45 males and 46 females, ranging from 17 to 92 years with a median age
      of 73 years. Pulselessness (96), coldness (94), pain (85), paraesthesia (45) and
      dysfunction (45) of the affected limb were the main symptoms. The right upper
      limb was more often affected (59/38, P < 0.05). An embolus originating from the
      heart was the reason for the ischaemia in 71 cases, while in 11 cases the
      occlusion was caused by a local thrombosis. In 15 cases the origin of the embolus
      remained unsolved. In five cases an additional arterial reconstruction was needed
      to restore the circulation. Reembolectomy of the same limb was needed in five
      cases, and additionally in two patients, a third embolectomy was unavoidable. A
      secondary humeral amputation was necessary for one patient. Eleven patients
      (11.3%) died within 30 days and of these nine did so from recurrent embolism. The
      mortality was not related to the duration of the ischaemia, but rather to
      patients' general condition. During a mean follow-up time of 50 weeks a good
      functional result was achieved in 78 cases (80.4%). The clinical results in
      ischaemia caused by embolism are markedly better than those of local thrombosis
      (P < 0.001).

PMID- 7645904
TI  - Outcome of thoracoabdominal aortic aneurysm surgery. Analysis of 27 consecutive
      cases.
AB  - Twenty seven patients underwent repair of a thoracoabdominal aortic aneurysm at
      our hospital during 1978-1993. Sixteen were elective and 11 emergencies. We used
      a temporary shunt and transsection of the proximal aorta between vascular clamps,
      so that the whole distal aorta with its branches was perfused through the shunt
      during suturing of the proximal anastomosis. The aortic branch arteries were
      revascularized by the step by step technique. Hospital mortality was 6/27 (22%)
      and two and five-year cumulative survival rates 74% and 52%. Late deaths were not
      related to aneurysm disease. Paraplegia developed in two patients. Distal aortic
      perfusion was used as a means of spinal cord preservation.

PMID- 7645906
TI  - Intraoperative sonography in patients with suspected liver metastases.
AB  - The correlation of preoperative sonography and intraoperative inspection and
      palpation of the liver with intraoperative sonography was studied in 77 patients.
      All underwent elective abdominal surgery for the treatment of verified malignant
      intra-abdominal tumours. Preoperative sonography findings differed from the
      intraoperative findings in 22 of the 77 patients (29%), intraoperative sonography
      being more reliable. Palpation differed from intraoperative sonography in 16 of
      77 patients (21%), in three of whom the findings at intraoperative sonography
      altered therapy. Intraoperative sonography was most effective in detecting small
      previously undetected, nonpalable lesions deep in the liver parenchyma. There
      were no complications due to sonography. We recommend intraoperative sonography
      as a safe and diagnostically effective procedure for routine use in abdominal
      surgery.

PMID- 7645907
TI  - Simo Antero Brofeldt--hospital leader, university teacher and military surgeon.
AB  - Simo Antero Brofeldt, Professor of surgery at the University of Helsinki from
      1933 to 1942, was active in the planning and building of the Finnish Red Cross
      Hospital. He was the first chief surgeon of the hospital from 1932 to 1942, and
      consulting surgeon to the Finnish army High Command during the Second World War.
      He contributed to the development of trauma surgery, was acknowledged as a superb
      organizer and served the defence forces with honour.

PMID- 7645908
TI  - Conservative versus operative treatment of appendicular abscess. Experience of
      147 consecutive patients.
AB  - One hundred and forty-seven consecutive patients who were treated for
      appendicular abscess were studied retrospectively, to evaluate conservative and
      operative treatment. 69 patients (47%) were primarily treated conservatively; of
      them six (9%) had to be operated on in the acute phase because of worsening of
      the symptoms. 78 patients (53%) were operated on primarily. Of them, 22 (28%) had
      complications, five (6%) needed a reoperation. Interval appendicectomy was
      performed in 45 patients (31%) 2-6 months after conservative treatment, and all
      healed well. Eighteen patients (12%) were treated conservatively only. Colography
      was performed in 48 patients after conservative treatment. In four, a tumour was
      suspected, but at operation no tumour was found in any of them. However, one
      caecal carcinoma was found at the interval appendicectomy, but in this case the
      colography did not reveal the tumour. In addition, five cases of Crohn's disease
      and one of diverticulitis were detected. Our findings suggest that if
      appendicular abscess is operated on in the acute phase, there may be more
      complications, but it is often not possible to make the correct diagnosis before
      operation. The routine of interval appendicectomy may be questioned, but adequate
      follow-up should be arranged. Laparotomy is indicated without delay when there is
      clinical suspicion of cancer, even if the colography does not reveal a tumour.
      For young asymptomatic patients conservative treatment with sufficient follow-up
      might be sufficient.

PMID- 7645909
TI  - Impact of tumour grade, stage, number and size, smoking habits and sex on the
      recurrence rate and disease-free interval in patients with transitional cell
      carcinoma of the bladder.
AB  - The recurrence rate and the time interval until the first recurrence were
      analysed in 169 consecutive conservatively treated patients with transitional
      cell carcinoma of the urinary bladder, in relation to initial tumour grade,
      number, size and stage, sex and smoking habits, at least five years after the
      diagnosis of the disease. The recurrence rate was higher among patients with more
      than three tumours and among patients with an invasive disease, while tumour
      size, histological grade and sex had no effect on the recurrence rate. The time
      until the first recurrence was found to be shorter among patients with an
      invasive disease and those with more than three tumours, and also among females.
      Smoking did not have any impact on the disease-free interval or on recurrence. We
      suggest that patients with multiple tumours are at great risk of recurrent
      disease. If invasion into muscle is found, the risk of recurrences will be high,
      and transurethral electroresection might not be an adequate form of therapy.

PMID- 7645910
TI  - Residual stones after percutaneous nephrolithotomy; sensitivities of different
      imaging methods in renal stone detection.
AB  - Kidneys of 35 renal stone patients treated with percutaneous nephrolithotomy
      (PNL) were examined at 12-36 months (mean 23 months) after the procedure by plain
      radiography (PR), conventional linear tomography (LT), computed tomography (CT),
      and ultrasonography (US) to find out the long-term stone-free rate as well as the
      accuracy of these imaging methods to detect residual or recurrent renal stones.
      The present series included 36 kidneys with a 56% postoperative stone-free status
      examined by plain radiography and a 58% one examined by linear tomography at 12
      36 months. CT showed 47% and US 72% of the kidneys to be stone-free,
      respectively. The sensitivity of CT was superior to plain radiography (P < 0.05),
      linear tomography (P < 0.05) or US (P < 0.001) in the detection of residual or
      recurrent stones after percutaneous nephrolithotomy analyzed statistically by
      McNemar's test. In the same group of 35 patients, which consisted of the above 36
      postoperative kidneys together with 19 contralateral kidneys, a total of 55
      kidneys were evaluated by the above methods, revealing 56 stones in 31 kidneys.
      Of these stones 95% were detected by CT, 70% by plain radiography, 68% by linear
      tomography, and 32% by renal US. Of the 55 kidneys, 14 contained 20 stone
      fragments smaller than 3 mm, and 26 kidneys carried 43 concrements smaller than 6
      mm. The sensitivities of the four imaging methods in the detection of these small
      fragments were as follows: plain radiography 60% and 60%, linear tomography 55%
      and 58%, CT 95% and 93%, and US 15% and 26%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7645911
TI  - Intramedullary nailing of tibial shaft fractures.
AB  - Sixty-four displaced tibial shaft fractures were treated using intramedullary
      nailing, either primarily or after an attempt at conservative treatment, which
      consisted of closed reduction under anaesthesia and immobilisation in a long-leg
      plaster cast. There were 37 closed and 27 open fractures. Three patients had a
      fracture of both tibiae. The median time period from the intramedullary nailing
      of the closed solitary fractures to union was about the same after primary
      nailing as after delayed nailing. Although the fractures were different in these
      groups, it is possible that the time spent in conservative treatment before
      intramedullary nailing brings no additional benefits. The incidence of deep
      infection in open fractures after primary nailing was 1/16. The fractures, in
      which an acceptable position could not be maintained using conservative methods,
      were mainly spiral in configuration and located in the distal third or at the
      junction of the middle and distal thirds of the tibia.

PMID- 7645912
TI  - Local tumour resection in interferon treated osteosarcoma patients.
AB  - Fifteen patients with primary classical osteosarcoma tumours are presented, all
      of whom have been operated on with local en bloc resection of the tumour mass in
      combination with adjuvant treatment with human leucocyte interferon. All patients
      have at present been followed up for more than fifteen years and half of them
      have shown no tumour recurrence. One patient committed suicide and eight died of
      generalized tumour disease. Two patients developed lung metastases five and eight
      years after primary surgery. This form of treatment, allowing limb preservation,
      is presented as an alternative to conventional ablative surgery providing that it
      is reserved for centres with specialized surgical teams.

PMID- 7645913
TI  - Long-term results of Smillie pin fixation of osteochondritis dissecans in the
      femoral condyles.
AB  - The purpose of this study was to determine the extent of secondary osteoarthritis
      after fixation of an osteochondritis dissecans fragment in the knee using Smillie
      pins as well as to assess the final outcome of the procedure. Eighteen patients
      treated for osteochondritis dissecans of the knee 10-34 years previously were re
      evaluated clinically and radiologically. Moderate secondary osteoarthritis was
      noted in 35% of the patients, and clinically unsatisfactory result was seen in
      44%. The remaining patients showed good or excellent clinical and radiological
      results at the follow-up.

PMID- 7645914
TI  - Modified distal metatarsal osteotomy for hallux valgus.
AB  - Sixty-three feet in 44 patients with a hallux valgus, which had been operated on
      using a modified distal osteotomy were reviewed after a mean follow-up of 4.6
      years. A modification of Mitchell's and Mommsen's osteotomies was used without
      any fixation material. The mean correction of the intermetatarsal angle was 2.6
      degrees and of the hallux valgus angle 5.2 degrees. Good subjective result was
      achieved in 90% of the feet. In six (9.5%) cases the hallux valgus angle was
      worse after the operation. The method used seems to be too unreliable to be
      continued. Patient selection was found to be of great importance. Hallux valgus
      angle of more than 40 degrees was less suitable for this kind of operation.

PMID- 7645915
TI  - Low molecular weight heparin (enoxaparin) compared with unfractionated heparin in
      prophylaxis of deep venous thrombosis and pulmonary embolism in patients
      undergoing hip replacement.
AB  - Prophylactic efficacy and safety of a low molecular weight heparin (LMWH) and
      those of conventional unfractionated heparin (UH) were investigated in a
      randomized study. Totally, 167 consecutive patients undergoing total hip
      replacement were allocated to two groups. Patients in the LMWH-group (n = 83)
      received a fixed dose of enoxaparin 40 mg once daily, starting 12 hours
      preoperatively and continuing for 10 days. Patients in the UH-group (n = 84)
      received UH 5000 IU twice a day subcutaneously (sc), starting two hours before
      operation and continuing for 10 days. Deep venous thrombosis (DVT) was diagnosed
      by bilateral ultrasonography and confirmed by venography. Proximal DVTs were
      observed in four patients of UH-group (4.8%) and in one of LMWH-group (1.2%, P >
      0.05). There was only one pulmonary embolism (PE) in a patient belonging to UH
      group (1.2%). Low rates of thromboembolic events could be explained, in addition
      to heparin prophylaxis, also by early mobilization and regional anaesthesia.
      Local tolerance (size of haematoma), blood loss and transfusion requirements
      during the operation and the postoperative period did not show differences
      between the two study groups. The results of our study indicate that enoxaparin
      once daily is an effective and safe form of DVT prophylaxis in patients
      undergoing elective hip replacement.

PMID- 7645916
TI  - Barrett's oesophagus and perforation of gastric tube ulceration into the
      pericardium: a late complication after reconstruction of oesophageal atresia.
AB  - 15 years after replacement of atretic segment with a gastric tube, perforation of
      an intrathoracic gastric tube ulcer into the pericardium, oesophago-pericardial
      fistula and severe mediastinitis developed in a 17-year-old male after
      reconstruction of oesophageal atresia using a retrosternal Heimlich-tube with a
      cervical oesophagogastric anastomosis. For six years he suffered from reflux
      oesophagitis and had Barrett's metaplasia in the cervical oesophagus. The patient
      had previously had one unsuccessful attempt to correct the oesophageal atresia at
      the age of two years using transverse colon. The two stage treatment included
      subtotal oesophagectomy, pericardiotomy, cervical oesophagostomy, gastrostomy,
      mediastinal and pericardial irrigation with antibiotics. After healing of the
      mediastinitis, the continuity of the alimentary tract was restored by using an
      isoperistaltic subcutaneous ileocolic segment. After a follow-up of five years
      the patient is well, without any oesophageal symptoms.

PMID- 7645917
TI  - Hepatic stab wound with retrohepatic vena cava and hepatic artery injuries.
AB  - A case of a hepatic stab wound with concomitant retrohepatic vena cava and
      hepatic artery injuries is presented. A direct non-shunting technique of caval
      repair was used. The management options of retrohepatic vena caval injuries, and
      the effect of hepatic artery inflow on liver regeneration after major hepatic
      resection are discussed.

PMID- 7645918
TI  - Interferon resistance is independent from copy numbers in benign HPV-induced
      lesions.
AB  - Interferons (IFNs) are successfully used in treatment of different human
      papillomavirus (HPV)-related diseases, such as condyloma acuminatum.
      Unresponsiveness can be seen in a number of patients which is related to a
      differential expression of early (E7) and late (L1) viral genes, according to our
      preliminary studies rather than to impaired IFN-signalling. The molecular basis
      for this differential expression might imply differential viral replication (copy
      numbers) in responder vs. nonresponder patients. PCR analysis revealed that the
      two groups did not differ significantly in HPV copy numbers before treatment. In
      contrast E7 and L1 levels significantly differed in responders versus
      nonresponders, regardless of copy numbers. Also, the IFN-mediated
      antiproliferative effect was mostly influenced by other factors rather than just
      the copy number. Our data imply that the unresponsiveness of certain patients to
      IFN treatment may relate to differential viral gene transcription rather than
      different copy numbers of infecting HIVs.

PMID- 7645919
TI  - Immunohistochemical detection of P-glycoprotein on frozen and paraffin-embedded
      tissue sections of normal and malignant tissues.
AB  - In this study the reactivity of the monoclonal antibodies (mabs) C 219, C 494 and
      4E3 was compared on frozen and paraffin-embedded normal tissues and tumors. On
      frozen tissues we used an indirect immunoperoxidase method, while on paraffin
      sections a streptavidin-biotin method without antigen retrieval methods was used.
      In normal tissues all mabs were reactive with colon epithelium in frozen and
      paraffin-embedded sections. The bile canaliculi in the liver showed the most
      extensive reaction with C 219 in frozen sections, and to a lesser extent with C
      494 and 4E3. C 219 reacted with the pancreatic acinar and ductal epithelium,
      whereas C 494 and 4E3 reacted predominantly in the stroma. The kidney showed
      positivity for all mabs in the collecting ducts and isolated solitary cells were
      reactive in the spleen. In the skin the eccrine part of the sweat glands was
      reactive for all mabs in paraffin sections. The lung, prostate and breast were
      negative for all mabs. Only in paraffin sections of various tissues did the C 494
      appear to be reactive with nerve fibers and ganglion cells. Colon cancers were
      positive for P-170 with all mabs tested. In breast carcinoma C 494 showed
      positive reactions in 8/26 frozen and 4/22 paraffin sections, while 4E3 was
      reactive with 20/25 frozen but only with 1/21 paraffin sections. C 219 gave
      similar results in frozen (22/26) and paraffin (17/26) sections of breast cancer.
      Ovarian carcinomas were positive with C 494 in 11/20 of the frozen and in 11/15
      of the paraffin sections, while 4E3 again reacted more weakly in paraffin (5/15)
      than in frozen (15/20) sections. C 219 gave positive reactions in all ovarian
      carcinomas in frozen (20/20) and paraffin sections (14/14). In the tumors, the
      most intense reaction for all mabs was obtained in the colon, followed by the
      ovary and breast. Enhanced staining was seen in paraffin sections for mab C 494
      in ovarian carcinoma. By demonstrating the presence of both an external and
      internal epitope on frozen sections, the combined use of 4E3 and C 219 gave
      complementary information about the expression of P-170.

PMID- 7645920
TI  - Immunohistochemical detection of ras P21 oncoprotein in human skin lesions.
AB  - This study was undertaken to investigate the role of the human ras family gene
      product [P21] in various benign, precancerous and malignant skin lesions. A
      streptavidin-biotin peroxidase method was performed using the monoclonal antibody
      (Mab)Y13259 in paraffin tissue sections of a total of 69 skin lesions (5 benign
      hyperplasias, 12 seborrheic keratoses, 9 solar keratoses, 20 basal cell
      carcinomas and 23 squamous cell carcinomas). The adjacent normal skin was also
      studied in all cases. The expression of ras P21 was evaluated and graded in
      relation to the intensity of cytoplasmic immunostaining and the percentage
      proportion of positive epidermal cells. The following findings were noted in this
      study: 1) The positivity of ras P21 increased towards the keratin layer,
      according to cell maturation, in all normal, hyperplastic and "borderline"
      lesions, and to a lower degree in the seborrheic ones. 2) Comparing B.C.C. and
      S.C.C., higher expression was demonstrated in the latter, probably due to the
      high percentage of the well differentiated component.

PMID- 7645921
TI  - Current aspects of the pathology of osteosarcoma.
AB  - Since the introduction of standardized chemotherapy protocols of osteosarcoma a
      lot of new aspects in prognosis and curability of these have best developed.
      Current subclassification which divided osteosarcoma into a conventional type and
      eleven important recognizable varieties is one of the reason for this success.
      Cytological grading also serves as a good indicator for the prognosis and is an
      important criterion for application of adjuvant chemotherapy. Several structure
      proteins of the extracellular matrix have gained importance in making the
      diagnosis of an osteosarcoma. Immunohistochemically and biochemically evaluations
      could show that different collagenous-proteins can be useful for the differential
      diagnosis of bone tumors. The integration of molecular pathologic methods into
      the structural morphologic findings will be helpfull in the identification of
      mutated structure proteins. Oncogenes and tumor suppressor genes are of major
      importance for the tumorigenesis of osteosarcoma. The prognostic significance of
      the inactivation of p53 and RBI gene remains to be elucidated. Resistance to
      chemotherapy is the major mechanism responsible for the failure of osteosarcoma
      treatment. The main cause for this failure is multidrug resistance, which is
      often related to a plasma membrane protein, the P-glycoprotein. Immunohistologic
      investigations of P-glycoprotein are not sufficient to demonstrate the possible
      association between overexpression of this protein and tumor progression.

PMID- 7645923
TI  - p53 protein detected by two different antibodies: relationship to proliferation
      and prognosis in acute lymphoblastic leukemia.
AB  - The expression of p53 protein was examined in a series of 69 children with acute
      lymphoblastic leukemia with two different monoclonal antibodies (Mab 1801 and
      240). p53 expression was detected with at least one antibody in 49 cases (71%),
      whereas only 19 cases (27%) were positive with both antibodies. Variability in
      the immunostaining could be observed depending on the antibody used. Mab 240 gave
      the highest rate of positive staining (58%), followed by 1801 with 39%. Positive
      staining with 1801 was significantly associated with decreased proliferation of
      tumor cells as measured by Ki-67 labelling, indicating that possibly the wild
      type p53 protein is preferably stained with this antibody. However, neither of
      the two antibodies has prognostic value or is correlated with histopathological
      parameters.

PMID- 7645922
TI  - Prognostic value of cathepsin-D expression in female breast cancer.
AB  - Expression of an acidic lysosomal protease, cathepsin-D (CD), was analysed
      immunohistochemically in a series of 151 breast carcinomas with special reference
      to its prognostic significance, Strong expression of CD was detected in 22% of
      cases. This intense expression was significantly associated with a number of
      established prognostic factors, including the non-ductal type of carcinoma (p =
      0.0243) and metastases at the time of diagnosis (p = 0.0068). On the other hand,
      high expression of CD was not related to the lymph-node status, tumour size,
      ER/PR content or histological grade. Patients with CD overexpression has a
      significantly lower survival probability (p = 0.0478) than did the patients with
      low expression of this protease. The relationship between the high expression of
      CD and short disease-free survival was almost significant (p = 0.0519). Intense
      immunostaining of CD was associated with a significantly impaired disease outlook
      in patients with confirmed lymph node metastasis (N+) (p = 0.0137) but not in
      those with negative lymph nodes (N-) (p = 0.0620). In Cox's multivariate
      analysis, expression of CD had no independent prognostic value over the
      conventional prognostic factors. The results suggest that expression of CD is of
      borderline significance in evaluating the intrinsic malignancy of female breast
      cancer in general. The potential of CD as a prognostic factor in specific
      subgroups of breast cancers will be the subject of further studies.

PMID- 7645924
TI  - Clinicopathological features of patients who died with second primary cancer
      after curative resection for gastric cancer.
AB  - The appearance of a second cancer in patients who had undergone curative
      operation for the first gastric cancer is one of the crucial problems for the
      clinician. We analysed data on 910 patients with gastric cancer treated with
      curative resection, with respect to the risk factors for second primary cancer
      and the prognosis. Of 910 patients, 69 (7.6%) died with a second primary cancer.
      In patients with a second primary cancer, there were more men and age was more
      advanced, compared to the survivors. The gastric tumor was larger, the serosal
      invasion was more prominent and lymphatic involvement was more frequent. The
      postoperative 5-year survival for patients with a second primary cancer was
      60.9%, the 10-year rate was 31.9% and the 15-year was 19.6%. Multivariate
      analysis revealed that risk factors for a second primary cancer was advanced age,
      male sex and a larger tumor. Our findings suggest that during the follow-up of
      patients with gastric cancer treated by curative resection and risk factors, a
      second primary cancer may occur in other organs, in addition to a recurrence of
      the first cancer.

PMID- 7645925
TI  - Significance of c-erbB-2 expression in normal and neoplastic epithelium of
      biliary tract.
AB  - There were few, but conflicting, reports dealing with the clinical significance
      of c-erbB-2 in biliary tract cancer. We evaluated the expression of c-erbB-2 in
      normal epithelium of bile ducts (n = 46), gallbladder cancer (n = 11), carcinoma
      of the ampulla of Vater (n = 18), and intrahepatic cholangiocarcinoma (CC) (n =
      18). c-erbB-2 protein is present in 63% (29/46) of surface epithelium in large
      and septal bile ducts, but not in peripheral small ducts. Overexpression of the
      gene product was found in 27.8% (5/18) of intrahepatic CC, 27.8% (5/18) of
      carcinoma of the ampulla of Vater, and 63.6% (7/11) of gallbladder cancer. But,
      there was no c-erbB-2 overexpression in the hyperplasia or atypical hyperplastic
      bile duct epithelium (p = 0.002). In terms of prognostic implication, expression
      of c-erbB-2 did not correlate to the histopathological grade (p = 0.60) and tumor
      stage (p = 0.63). The results indicate that c-erbB-2 protein may play some roles
      in physiology of normal bile ducts. Overexpression of the gene product occurs in
      one forth to about two thirds of carcinoma of biliary tract, and may be used as
      phenotypic marker for neoplastic transformation. However, the gene product may
      not be important in the aggressive behavior of tumor.

PMID- 7645926
TI  - Oral high-dose medroxyprogesterone acetate treatment for recurrent breast cancer.
AB  - Oral high-dose medroxyprogesterone acetate (MPA) treatment (600, 800, 1200 mg/day
      or changed dosage) was given to 49 patients with recurrent breast cancer from
      January 1979 to December 1992. The overall response rate to MPA was 38.8%
      (19/49). The response rate in the soft tissue was significantly higher compared
      with that in bone metastases or in visceral metastases. MPA was effective on
      patients both with or without previous treatment. Several side effects were
      recognized, but they were mild and tolerable. These results demonstrate that MPA
      is effective when used as first line or second line treatment.

PMID- 7645927
TI  - Clinical utility of tissue polypeptide antigen determination in lung cancer
      management.
AB  - In view of the fact that pulmonary malignancies still represent an important
      cause of tumor death and that the high rate of unsuccessful treatment may be
      partly due to the late clinical presentation, efforts should be spent not only to
      develop new and effective treatments but also to improve early diagnosis and to
      identify prognostic factors and parameters useful for the monitoring of the
      treatment. Tumor markers, if used properly, can provide a useful support for the
      management of patients suffering from various malignancies, including lung cancer
      patients. The clinical significance of one of the most widely used tumor markers,
      Tissue Polypeptide Antigen (TPA), has been reviewed and showed this marker to be
      useful to the clinician for the management of patients with pulmonary malignancy,
      as a complementary tool for diagnosing and staging the tumor as well as for
      monitoring treatment response or relapse occurrence.

PMID- 7645928
TI  - Recurrence patterns in patients with early stage cervical cancer treated with
      radical hysterectomy and external pelvic irradiation.
AB  - One hundred and fifty patients with clinical FIGO stage IB-II cervical cancer who
      underwent radical surgery followed by external pelvic irradiation between 1978
      and 1991 were reviewed. Until June 1994, 28 (18.7%) patients developed recurrent
      disease. Seventeen (60.7%) of them experienced a pelvic failure, 7 (25.0%) an
      extrapelvic failure and 4 (14.3%) both a pelvic and an extrapelvic failure. The
      median time to recurrence was 16 months for patients with pelvic failure (range =
      4-50 months), 27 months for those with extrapelvic failure (range = 6-49 months),
      and 21 months for those with both pelvic and extrapelvic failure (range u 8-56
      months). Recurrence rates were significantly related to surgical-pathologic
      stage, tumor size and lymph node status, but not to histologic type. An
      extrapelvic recurrence, alone or associated with a pelvic failure, was found in
      0.9% of 117 patients with negative lymph nodes, 6.2% of 16 patients with one or
      two positive lymph nodes, and 52.9% of 17 patients with three or more positive
      lymph nodes, (p = 0.0001). It is worth noting that 9 (81.8%) out of the 11
      patients who developed extrapelvic recurrences had three or more involved lymph
      nodes. The number of positive lymph nodes (p = 0.0001) and the tumor size (p =
      0.0046) were independent prognostic variables for disease-free survival.

PMID- 7645930
TI  - Radioimmunoassisted follow-up and surgery vs traditional examinations and surgery
      after radical excision of colorectal cancer.
AB  - The authors report their experience in the radioimmunodetection of recurrent
      colorectal cancer in comparison with traditional examinations. 485 patients were
      studied after radical surgery for colorectal cancer: 168 (Group 1) were studied
      with a radioimmunoassisted follow-up plan including: Immunoscintigraphy (IS),
      serum markers assays, Radioimmunoguided Endoscopy (RIGE), Intraoperative
      Radioimmuno-localization (IORIL) in case of reoperation; 317 (Group 2) underwent
      a protocol with traditional examinations. In 24 patients of Group 1 IS was
      performed even at the time of their admission for primary cancer. 7 patients
      underwent RIGE for primary cancer and 16 in the follow-up. IORIL was performed in
      12 patients with primary cancer and in 16 in the course of reoperation. The
      radioimmunodiagnostic methods were performed after a single administration of the
      radiolabeled MAb (111In F(ab')2 a-CEA and 111In B72.3). The radioimmunoassisted
      follow-up plan detected a greater number of recurrences than traditional
      examinations (27% vs 13%). The rates of radical reoperation in Group 1 and 2 were
      61% and 37% respectively. 33% of the patients of Group 2 were alive 24 months
      after radical reoperation vs 62.5% of the patients of Group 1. Immunoscintigraphy
      demonstrated a good sensitivity and specificity, mainly in the detection of
      pelvic recurrences (sens. 92%, spec. 84%). The radioimmunoassisted follow-up plan
      was well accepted by the patients. RIGE led to the detection of 3 periluminal
      recurrences of rectal cancer that traditional investigations failed to
      demonstrate and in 5 cases influenced the patients management. IORIL detected
      minimal tumor foci (2 mm.) where pre and intraoperative study were negative,
      while the histopathologic examination gave evidence of tumor. Considering that
      the costs of the radioimmunodiagnostic methods and of traditional examinations
      are very similar, we can conclude that the radioimmunoassisted follow-up plan has
      a favorable cost/benefit rate and a remarkable impact on the treatment of
      patients with colorectal cancer.

PMID- 7645929
TI  - Etoposide, leucovorin and 5-fluorouracil in advanced gastric cancer: a phase II
      study.
AB  - It has been suggested that the combination of etoposide, leucovorin and 5
      fluorouracil (ELF) is very active in the treatment of advanced gastric cancer in
      elderly patients. The aim of this study was to confirm the efficacy and to
      investigate the toxicity of the ELF-regimen in patients of all ages. Thirty
      patients with advanced gastric adenocarcinoma were treated with leucovorin (300
      mg/m2), etoposide (100 mg/m2) and 5-FU (500 mg/m2) for 3 consecutive days every 4
      weeks in a phase II study. Reevaluation of measurable disease was done after 3
      cycles. A partial response was shown in 8 (27%) patients. An improvement of the
      Karnofsky Performance Status was observed in 10 (33%) patients. The mean survival
      amounted to 8 months (range 2-24). Toxicity was mild. No grade 4 toxicity nor
      chemotherapy-related mortality were observed. It is concluded from this phase II
      study that the ELF-regimen is an active palliative treatment for advanced gastric
      cancer, with mild toxicity.

PMID- 7645931
TI  - Prognostic significance of ferritin expression in colorectal adenocarcinoma.
AB  - In recent years, there has been considerable interest in ferritin as an oncofetal
      protein. However, the clinical significance of ferritin expression in cancer
      tissues remains unknown. We performed an immunohistochemical study to examine the
      expression of ferritin in colorectal adenocarcinoma (n = 104). A total of 95 out
      of 104 (91.3%) colon cancers were positive for ferritin expression. The degree of
      immunoreactivity has no significant correlation with tumor grade (p = 0.964),
      size (p = 0.659), serosal invasion (p = 0.331), nodal metastasis (p = 0.955),
      distant metastasis (p = 0.354) and DNA ploidy status (p = 0.126), but there was a
      strong association between ferritin expression of tumor cells and stromal
      mononuclear cell infiltration (p = 0.004). In terms of prognostic significance,
      multivariate analysis showed that nodal metastasis (p = 0.0123) and distant
      metastasis (p = 0.0237) were independent poor prognostic factors. However, there
      was no significant difference in survival between patients with weak and strong
      ferritin expression in cancer tissues (p = 0.3766). The results indicate that the
      majority of colorectal adenocarcinomas exhibit ferritin expression. The grade of
      ferritin expression is strongly associated with stromal mononuclear cell
      infiltration, but has no significant correlation with any staging parameters or
      the survival of cancer patients.

PMID- 7645932
TI  - Identification of high-risk groups in endometrial carcinoma stage I-II. A
      combination of DNA- and steroid receptor-measurements identifies early deaths
      from the disease.
AB  - BACKGROUND: Treatment of endometrial carcinoma has not improved during the last
      decades, due to the already good results. Such therapy has been a compromise,
      strong enough to cure some of those in need of harder treatment, but weak enough
      not to cause too severe side-effects. One way of solving the problem of
      overtreatment is to identify those in real need of a harder regimen. Generally,
      the histopathologic picture and the depth of myometrial invasion of the tumour
      have been used. However, this often means a too large high-risk group, often
      exceeding 50% of the patients. METHODS: Steroid receptor concentrations and later
      DNA-measurements have been increasingly used to identify high-risk groups not,
      however, in combination. In 156 patients with endometrial carcinoma, both
      estradiol receptor concentration and flow cytometrically estimated DNA content
      were measured on all patients and the patients were followed-up for over five
      years. RESULTS: By using the number of DNA-populations (ploidy) we could identify
      a small high-risk group (28%) with a death frequency of 35%. This small group
      could be further divided, by using the estradiol receptor concentration, into an
      extremely small high-high-risk group (11%) consisting of 17 patients of whom 9
      died from the disease within 5 years, almost all of the deaths occurring within 2
      years. CONCLUSION: Thus histopathology was reduced to merely identifying cancer
      but DNA- and estradiol receptor measurements in combination could identify an
      extremely small high-risk group, with almost all deaths occurring within 2 years.

PMID- 7645933
TI  - Perineural infiltration by cutaneous squamous cell carcinomas of the head and
      neck.
AB  - In this paper six cases of cutaneous squamous cell carcinoma of the head and neck
      region with histologically-documented perineural tumoral infiltration are
      presented. Most patients showed recurrent disease during follow-up and have been
      treated with surgery and radiotherapy with or without systemic chemotherapy. The
      prognostic implications of perineural neoplastic infiltration as well as of
      therapeutic options are discussed.

PMID- 7645934
TI  - Correlation of P-glycoprotein overexpression and cellular prognostic factors in
      formalin-fixed, paraffin-embedded tumor samples from breast cancer patients.
AB  - BACKGROUND: P-glycoprotein overexpression seems to play a prognostic role
      independent from its association with multidrug resistance. We have been able to
      verify this previously on fresh-frozen tumor samples, but up to now P
      glycoprotein detection on formalin-fixed, paraffin-embedded material has
      generally been unsatisfactory. METHODS: Two distinct groups of previously
      untreated mammary carcinomas were studied for P-glycoprotein expression by means
      of immunohistochemistry, using the NCL-p-GLYp polyclonal antibody, carried out on
      slides from archival, paraffin-embedded material. The first group was composed of
      15 tumors expressing at least three out of four factors indicative of a worse
      prognosis: c-erb-B2, mutant p53, cathepsin-D and PCNA (proliferating cell nuclear
      antigen). The control group was composed of 16 tumors lacking expression of any
      of these proteins. RESULTS: There was a statistically significant difference in
      survival (Fisher's exact test, p = 0.0036) between both groups. All four patients
      who died during the follow-up period (mean 55.1 months) belonged to the first
      group. Three of these patients harbored tumors with the highest level of
      expression of P-glycoprotein. This association between P-glycoprotein
      overexpression and prognosis was also statistically significant (Fisher's exact
      test, p = 0.0059). CONCLUSION: These results, obtained from a group of mostly
      operable tumors stratified for cellular risk factors, complement those previously
      reported by us for locally advanced, inoperable breast cancer only, using fresh
      frozen tissue. P-glycoprotein again seems to play a prognostic role, independent
      of its involvement in multidrug-resistance. The technique used by us yielded
      useful results on formalin-fixed, paraffin-embedded archival tumor samples. This
      opens the possibility for larger studies on populations with a closed follow-up.

PMID- 7645935
TI  - Magnetic resonance imaging in the preoperative evaluation of suspected ovarian
      masses.
AB  - Meticulous pretreatment evaluation is basic to the successful management of
      suspected ovarian masses. Among currently available imaging techniques,
      sonography and computerized tomography are the most important diagnostic
      modalities. The purpose of our study was to determine whether magnetic resonance
      imaging provided additional information on masses in the true pelvis. 73 patients
      with masses in the true pelvis underwent preoperative magnetic resonance imaging.
      MRI was done with a 1.0 T supraconductive magnet (Magnetom Impact, Siemens). The
      results obtained were compared with sonographic (transabdominal and
      transvaginal), intraoperative and histopathologic findings. MR images were
      evaluated for their information on differentiation between benign and malignant
      neoplasm, tumor staging, lymph node involvement, peritoneal spread, local
      extension and organ relation. MRI correctly characterized malignant and benign
      tumors in 97% of cases versus 81% on ultrasound. The site of the primary tumor
      was correctly diagnosed in 94% of cases on MRI images versus 86% on ultrasound
      images. Invasion of adjacent intestinal segments as well as peritoneal
      carcinomatosis and omental metastases (metastasis > 1 cm) were also detected in
      the majority of cases. Based on our results MRI performs well at lesion detection
      and characterization in the evaluation of suspected ovarian masses. MRI should be
      considered in the investigation of patients with complicated findings on
      ultrasound.

PMID- 7645936
TI  - Tissue polypeptide specific antigen and cancer associated serum antigen in the
      follow-up of ovarian cancer.
AB  - 420 clinical and serological examinations prior to surgery and during follow-up
      were performed in 30 patients suffering from ovarian cancer. The population
      consisted of three FIGO stage Ia, nine stage Ic, four stage II and fourteen stage
      III cases. Serous carcinoma of the ovary, mucinous carcinoma and other kinds of
      ovarian cancer were found in 16, 9 and 5 cases, respectively. The serum levels of
      the tumor markers tissue polypeptide specific antigen (TPS), cancer associated
      serum antigen (CASA) and carbohydrate antigen 125 (CA 125) were determined. Cut
      off values of 97 U/l, 4 U/ml and 35mU/ml for TPS, CASA and CA 125, respectively,
      were selected according to the 95% of serum concentrations measured in healthy
      controls. Sensitivity, specificity, PPV and NPV of CA 125 were 75%/96%/69%/92%,
      respectively. Sensitivity, specificity, PPV and NPV of TPS were 67%/84%/59%/90%,
      respectively. CASA showed a sensitivity of 58%, specificity of 96% and a PPV and
      NPV of 73%/94%, respectively. The combination of TPS and CA125 increased the
      sensitivity to 81%, reaching a specificity of 82% and a PPV and NPV of 58/96%,
      respectively. The combination of CASA and CA125 showed a sensitivity,
      specificity, PPV and NPV of 88/85/65/96%, respectively. Twelve patients developed
      recurrence of disease after response to primary treatment. TPS, CASA and CA 125
      detected recurrent disease in six, two and four cases, respectively. For TPS mean
      lead time was 4.6 months (range 2-18 months), for CASA 1.7 months (range 1-6
      months), and for CA 125 3.5 months (range 1-24 months. As a matter of fact TPS
      never showed lead time effects in patients without elevated pretherapeutic
      levels. A combination of all makers showed a mean lead time of 6.72 months.
      Detection of recurrent disease by CA 125 is improved when CA 125 is used in
      combination with TPS, especially in those patients with pretherapeutically
      elevated TPS serum levels.

PMID- 7645937
TI  - DNA content of prostatic cancer measured by flow cytometry in patients undergoing
      radical prostatectomy.
AB  - The biological behavior of prostatic cancer is influenced by many host and tumor
      factors. The proliferative activity of the malignancies can be one of those
      parameters which serve as the basis to estimate prognosis and design treatment.
      Here, DNA content and S-phase fraction of prostatic cancer samples obtained by
      radical prostatectomy from 46 patients were related to other known tumor
      characteristics (PSA, staging, grading). Nuclei from the paraffin embedded
      materials were isolated with overnight trypsin-ribonuclease mixture digestion.
      DNA content and cell cycle distribution were determined by flow cytometry. A
      correlation was found between the PSA concentration, grading and staging on the
      one hand and S-phase fraction on the other. DNA content correlated with grading.
      No kinetic parameter correlated with the nodal involvement. Due to the
      association between abnormal DNA content plus SPF > 5% with advanced stage and
      less differentiated appearance of the tumor, we can conclude that these
      parameters are useful to estimate prognosis.

PMID- 7645938
TI  - Cytokine combinations for induction of antigen-specific cytolytic T lymphocytes
      from peripheral blood lymphocytes.
AB  - We studied effects of varied cytokine combinations on allogeneic cytotoxic T
      lymphocyte (CTL) generation in a mixed lymphocyte-tumor cell culture. Sensitized
      with allogeneic melanoma cell line (MM-8.1 or MM-28), peripheral blood
      mononuclear cells (PBMC) were cultured in medium containing various combinations
      of cytokines that included human recombinant interleukin-2 (rIL-2) alone (MB-2),
      rIL-2 and rIL-4 (MB-2,4) and rIL-1, rIL-2, rIL-4 and rIL-6 (MB-1,2,4,6).
      Lymphocytes proliferated for more than 50 days and manifested stimulating cell
      specific cytotoxicities in 1 of 5 cultures with MB-2, in 4 of 5 with MB-2,4 and
      in 5 of 5 with MB-1,2,4,6. Lymphocytes grew up to 10(6) fold in culture with MB
      2,4 or MB-1,2,4,6 at day 90-100. Stimulating cell MM-8.1 (HLAABC+,DR-) induced
      CD3+, CD8+, CD56- CTLs and MM-28 (HLA-ABC+, DR+) mainly generated CD3+, CD4+,
      CD56- CTLs. Monoclonal antibodies against HLA-ABC and HLA-DR molecules suppressed
      the stimulating cell-specific cytolytic activity of CD8+ and CD4+ CTLs,
      respectively. These data indicate that combination of rIL-1, rIL-2, rIL-4 and rIL
      6 offer an efficient system to generate allogeneic, tumor-specific CTLs from
      PBMCs and that HLA molecules expressed on stimulating cells play an important
      role in CTL generation.

PMID- 7645939
TI  - Inhibitory action of ganglioside GM3 on murine neuroblastoma cell proliferation:
      modulating effect of fetal calf serum.
AB  - Exogenous gangliosides have been shown to exert a regulatory influence on the
      proliferation and differentiation of several cell lines in tissue culture. The
      effect of ganglioside GM3 on C-1300 murine neuroblastoma (MNB) cell proliferation
      and the modulating action of fetal calf serum (FCS) concentration in the culture
      media have been investigated. MNB cells were cultured in DMEM containing 1, 2.5,
      5 or 10% FCS, and incubated with GM3 at concentrations ranging from 1.95 to 500
      microM. Cell proliferation was assayed 4 days after the addition of GM3 using the
      CellTiter 96 Non-Radioactive Cell Proliferation Assay. GM3 inhibited MNB cell
      proliferation in a dose-dependent manner regardless of the FCS concentration in
      the culture media. However, the magnitude of this inhibitory effect was inversely
      proportional to the FCS concentration in the culture media. The addition of
      albumin to MNB cells cultured in DMEM containing 1% FCS exerted no effect on the
      antiproliferative action of GM3. FACS cell cycle analyses demonstrated that MNB
      cultured in DMEM containing 1% FCS had a higher proportion of cells in the G0/G1
      compartment when compared to those cultured in 10% FCS. The enhanced response of
      MNB cells to GM3 observed in 1% FCS, may be due to a preferential action on cells
      in the G0/G1 stage of the cell cycle. These studies have demonstrated that the
      ganglioside GM3 inhibited MNB cell proliferation in tissue culture and this
      effect was modulated by FCS concentration in the culture media. Since protein
      binding of GM3 by FCS does not appear to be the primary mechanism by which FCS
      exerts its antagonistic effects, we hypothesize that this may be due to the
      opposing action of stimulatory growth factors present in FCS.

PMID- 7645940
TI  - EGF-effects in vitro and in vivo on a carcinoma cell line rich in EGFR.
AB  - T-CAR1 is a human carcinoma cell line established from a brain metastasis. The
      tumour cells overexpress EGFR and contain an amplified EGFR gene. In vitro in the
      presence of 5% human serum the tumour cells grow as adherent cells in monolayer.
      Shortly after exposure to EGF a large number of tumour cells round up and detach,
      whereas some remain adherent. At the same time a redistribution of actin occurs.
      Cytochalazin B prevented this reaction, which indicates that actin is involved in
      the detachment of the tumour cells. The EGF-detached tumour cells however, did
      not differ from the tumour cells which remained adherent after EGF-exposure with
      regard to parameters such as growth in soft agar, growth response to EGF, tumour
      necrosis factor-alpha, interferon-gamma, and carmustin (BCNU), level of EGFR gene
      expression and EGFR gene amplification, S-phase fraction, and amount of DNA. It
      was speculated whether the EGF-induced cellular detachment in vitro could be
      correlated to metastatic potential in vivo or not. In order to address this
      issue, in vivo studies with subcutaneous T-CAR1 tumours in nude mice were
      performed. Administration of EGF resulted in growth stimulation in contrast to
      growth inhibition in vitro, whereas no effect of EGF on the metastatic potential
      was observed. Thus, the EGF-mediated tumour cell detachment seems to be
      restricted to in vitro conditions only.

PMID- 7645941
TI  - Transcriptional activation of the c-myc oncogene in the T-47D mammary cancer
      cells by conditioned media from embryonic mouse fibroblasts (BALB/c-3T3). Effect
      of the antiestrogen ICI 164,384.
AB  - The effects of the conditioned medium (CM) of embryonic mouse fibroblast (BALB/c
      3T3) cells (clone A31) on the mRNA of the c-myc oncogene of the hormone-dependent
      T-47D mammary cancer cells were explored. After 6h incubation a significant
      stimulation of c-myc expression was observed with a 10% v/v concentration of CM,
      and the effect was even higher using a CM concentration of 30% v/v. It is
      suggested that this action of CM could be related to the stimulatory effect on
      proliferation and DNA synthesis induced by the CM, as was recently demonstrated
      for the T-47D cells. It was also observed that the antiestrogen ICI 164,384 (5 x
      10(-6) M) can inhibit the stimulatory action of CM on c-myc expression. It is
      concluded that the fibroblast mouse embryonic cells contain and secrete factor(s)
      involved in the mechanism of proliferation of human hormone-dependent mammary
      cancer cells.

PMID- 7645942
TI  - New platinum complex compounds with reduced nephrotoxicity discovered in long
      term histoculture of human renal cortical tissue.
AB  - Cisplatinum is often effective in cancer treatment, but potent nephrotoxicity
      limits its clinical use. We have synthesized six new platinum compounds with the
      goal of reducing toxicity while maintaining efficacy. We initially tested drugs
      at 5 x 10(-4)M with 48 hours exposure in monolayer cultures of primary rabbit
      proximal tubular cells and human renal cortical cells with the MTT endpoint to
      measure toxicity. Drug concentration of 10(-3)M, 10(-4)M and 10(-5)M with 72
      hours exposure were used for human renal cortical tissues in 7 week sponge-gel
      supported histoculture with toxicity measured by the glucose-consumption
      endpoint. From these studies, we determined that the new platinum drugs have
      lower nephrotoxicity than cisplatinum.

PMID- 7645943
TI  - Regulation of protein synthesis in human cells exposed to extreme hypoxia.
AB  - Protein synthesis was recorded in NHIK 3025 cells when cultured either during
      extremely hypoxic conditions or following reoxygenation. The rate of total
      protein synthesis in NHIK 3025 cells was found to be reduced to 30-40% of the
      rate in control cells within 1 h after the start of hypoxia. After reoxygenation,
      the rate of total protein synthesis was found to increase rapidly back to the
      control level. To reveal the stage of regulation of hypoxia associated proteins
      (HAP), mRNA was isolated from NHIK 3025 cells and translated in an in vitro
      translation kit. The results indicated that the relative amount of mRNA, of at
      least two HAP (80 and 45 kD), was increased under extremely hypoxic conditions
      ([O2] < 4ppm). This implies that some HAP are regulated pre-translationally.

PMID- 7645944
TI  - Protein kinase inhibitors exert stage specific and inducer dependent effects on
      HL-60 cell differentiation.
AB  - The human promyelocytic leukemia cell line HL-60 was induced to differentiate to
      mature granulocytic cells by dbcAMP or RA. The influence of distinct protein
      kinases during different stages of this differentiation was studied by the use of
      H8, staurosporine and genistein as inhibitors of PKA, PKC and PTK respectively.
      In dbcAMP-mediated differentiation, the PKA activity of uninduced cells is
      crucial for the induction of differentiation, but therefore its significance
      drastically declines and a more important role is played by PKC and PTK. In RA
      mediated differentiation, the native state of PKA and PKC activities are
      necessary and of similar importance for induction. However, the differentiation
      is enhanced when, following induction, the activities of PKA and PTK are normal
      and the activity of PKC, in contrast, is temporary suppressed. At the phenotypic
      stage the effect of inhibition of protein kinases on maturation is in the order
      PTK > PKC > PKA for the dbcAMP-mediated differentiation and PKC > PKA > PTK for
      the RA-mediated differentiation. The results indicate that protein kinase
      activities during differentiation are stage specific and this specificity depends
      on the inducer used.

PMID- 7645945
TI  - Taxol inhibits growth of mesothelioma xenografts.
AB  - BACKGROUND: In vitro tests measuring inhibition of adenosine triphosphate
      activity predicted three mesothelioma xenografts would be sensitive to taxol.
      PURPOSE: The in vivo therapeutic efficacy of taxol was tested in nude mice
      carrying the subcutaneous tumors. METHODS: Once tumor growth reached 100mm3 in
      size, intraperitoneal taxol, 30 mg/kg, on a day 1, 4, and 8 schedule, was
      administered to mice bearing subcutaneous mesothelioma xenografts. RESULTS: Taxol
      inhibits the growth of all three cell lines. It produces actual tumor regression
      including some complete responses. CONCLUSIONS: Taxol is an active drug against
      mesothelioma. The in vitro cell lines and the in vivo system are useful tools for
      screening and developing new treatments for mesothelioma.

PMID- 7645946
TI  - Structure-activity relationship of caffeic acid analogues on xanthine oxidase
      inhibition.
AB  - Caffeic acid has been reported to have activity on xanthine oxidase inhibition
      which is related to several diseases, e.g. gout, hepatitis and tumors. Based on
      this study, the alpha, beta-unsaturated COOH moiety in the molecule of caffeic
      acid plays a very important role on the xanthine oxidase inhibition because
      hydrocaffeic acid was inactive and the activities of coniferyl aldehyde and
      coniferyl alcohol were reduced as compared with ferulic acid. Moreover,
      chlorogenic acid showed a weaker activity than caffeic acid. On the other hand,
      the phenolic OH group present in the molecule of caffeic acid makes an important
      contribution to the activity, e.g. transcinnamic acid in which the absence of the
      phenolic OH group in the structure reduced its activity as compared with caffeic
      acid. Ferulic acid, isoferulic acid and 3,4-dimethoxy cinnamic acid also had
      reduced activity due to the methoxy groups replacing the phenolic OH group in the
      structures. However, m-coumaric acid displayed the strongest activity (IC50 =
      63.31 microM) and induced uncompetitive inhibition with respect to the substrate
      xanthine (Ki = 21.568 microM). Caffeic acid (IC50 = 74.6 microM) showed the
      second strongest activity, followed by p-coumaric acid (IC50 = 111.09 microM).

PMID- 7645947
TI  - Chemoprevention of chemically-induced mammary carcinogenesis by indole-3
      carbinol.
AB  - Indole-3-carbinol, a component of cruciferous vegetables, was evaluated for it
      efficacy in the prevention of chemically-induced mammary tumors using three
      different protocols. Because this compound was unstable, it was administered by
      gavage rather than in the diet. A preliminary dose range study revealed that dose
      levels of 100 and 50 mg/day, 5x/week, were not toxic to female Sprague-Dawley
      rats. Initial studies in the DMBA model showed that administering indole-3
      carbinol during the initiation and promotion phases were highly effective
      chemopreventive methods (91-96% reduction in cancer multiplicity). Subsequent
      studies showed that the administration of indole-3-carbinol only during the
      initiation phase (7 days prior to until 7 days post DMBA) was also highly
      effective as a chemopreventive agent. Determination of enzyme levels in the
      livers of animals treated long-term with indole-3-carbinol showed high levels of
      induction of various phase I and phase II drug metabolizing enzymes. Finally,
      indole-3-carbinol when administered both prior to and after MNU (a direct acting
      carcinogen) caused a significant decrease (65%) in mammary tumor multiplicity.
      These results support previous studies that indole-3-carbinol can prevent mammary
      carcinogenesis by direct and indirect acting carcinogens. Therefore, indole-3
      carbinol might be a good candidate for chemoprevention of breast cancer in women.

PMID- 7645948
TI  - Human tumors are methionine dependent in vivo.
AB  - Methionine-dependence is a tumor-specific biochemical defect expressed by the
      inability or decreased ability of tumors to grow under the condition of
      methionine-depletion. Many reports have shown that methionine-dependence occurs
      in human tumors of all types, including fresh surgical specimens in vitro.
      However, in vivo determinations of methionine-dependence have thus far been made
      only in rodent malignant tumors using methionine-deficient diets. We report here
      for the first time that human cancer xenografts in nude mice are methionine
      dependent and when fed a methionine-free diet tumor growth is greatly inhibited.
      The body weight of mice on the methionine-free diet was found to be maintainable
      by once-per-week administration of methionine. The data presented here suggest
      that methionine-dependence can be an important target for human cancer treatment.

PMID- 7645949
TI  - Differential oncogene expression and susceptibility to apoptosis in the human
      leukemia HL60 cell lines: implications for etoposide resistance.
AB  - Mechanisms of etoposide (VP-16) resistance have been evaluated in a human
      promyelocytic leukemia HL60 cell line. HL60 resistant (HL60/AR) cells were
      selected for resistance with adriamycin and were 250-fold resistant to VP-16. We
      have found that while a significantly higher (10 to 15-fold more) dose of VP-16
      was required to induce similar amounts of SDS-KCI-precipitable DNA-protein
      complex formation in the resistant cell line, there was no difference in the
      repair of VP-16-induced DNA damage, indicating that differential DNA repair was
      not involved in VP-16 resistance in HL60 cells. VP-16 treatment significantly
      inhibited c-myc expression and induced c-jun and c-fos expressions in sensitive
      cells. In contrast, VP-16 had no effect on c-myc, c-jun or c-fos expressions in
      resistant cells. The level of bcl2 oncogene was similar in both cell lines;
      however, treatment with VP-16 resulted in a time- and dose-dependent degradation
      of the genomic DNA into oligo-sized DNA only in the sensitive cells, indicating
      that differential expressions of oncogenes (c-myc, c-jun, and c-fos) and
      susceptibility to apoptosis may play important roles in the sensitivity and
      resistance to VP-16 in HL60 cells.

PMID- 7645950
TI  - Antiproliferative effects of four different cytokines on renal carcinoma cell
      lines.
AB  - The effect of alpha-Interferon (alpha-IFN), gamma-interferon (gamma-IFN), tumor
      necrosis factor alpha (TNF-alpha) and interleukin-2 (Il-2) on growth of two renal
      cancer cell lines (DNT-11, HTB-44) was studied. Cell proliferation was measured
      by a tetrazolium based microculture assay (MTT) after incubation of tumor cells
      with different concentrations of these 4 cytokines over 72 hours. TNF-alpha
      showed no antiproliferative effect when cell line DNT-11 was tested, even at high
      concentrations of 1.000 ng/ml. Proliferation of the other cell line (HTB-44) was
      only slightly reduced (15%) at 100 ng/ml; a tenfold increase of TNF concentration
      could not improve these results. The antiproliferative effect of alpha-IFN was in
      the range of 22-26%. When gamma-IFN was used, both cell lines showed reduction of
      proliferation between 26% and 37%, respectively. Kinetic studies revealed that
      prolongation of incubation time for more than 72 hours was not able to improve
      these results. Il-2 did not influence cell proliferation of either cell line
      tested, even at high concentrations, as expected.

PMID- 7645951
TI  - 4'-Epi-doxorubicin and hyperthermia in a murine mammary carcinoma: influence of
      the dose and fractionation.
AB  - Our aim was to analyse the dose-response rate of 4'-epi-doxorubicin (EP) alone
      and of EP combined with hyperthermia (HT) treatments in tumor-bearing mice. A
      spontaneous mammary carcinoma, transplanted into the right foot of female hybrid
      (C3H/RIxDBA/2J) mice, was used. EP (from 5 to 30 mg/kg) was administered i.p. and
      local HT (45-60 minutes at 42 or 43 degrees C) was carried out. Mice were treated
      with EP and/or HT in 1, 2 or 3 doses at 8 day intervals; in the case of 3 HT
      treatments EP was administered before the first or before each HT session (same
      EP total dose). When EP was given alone, in 1 or 2 fractions, results showed a
      clear dose-response relationship: tumor growth delay depended on the total dose
      only. Combining different EP single doses and 1 HT treatment (43 degrees C), an
      additive effect and perhaps a synergistic effect at the highest doses was
      observed. Among all tested combinations, the best results were observed combining
      3 HT with only 1 EP treatment.

PMID- 7645952
TI  - Medroxyprogesterone-acetate reverses the MDR phenotype of the CG5-doxorubicin
      resistant human breast cancer cell line.
AB  - In malignant cells multidrug resistance (MDR) is frequently associated with the
      expression of a 170 KDa P-glycoprotein (P-gp) in the plasma membrane. P-gp acts
      as an ATP-dependent efflux pump causing a decreased intracellular accumulation of
      structurally unrelated natural anticancer agents such as anthracyclines.
      Doxorubicin (DX) resistance is mostly related to the multidrug resistance gene
      product P-gp. In our experiments the revertant activity of medroxyprogesterone
      acetate (MPA) in comparison to that of the well known revertant agent verapamil
      (VRP) was investigated. In vitro tests were carried out on a DX-resistant variant
      (CG5/DX) obtained in our laboratory from the parental CG5 human breast cancer
      cell line by continuous exposure to the drug. The ability of MPA to modulate
      intracellular DX accumulation and to reverse MDR was evaluated. MPA appeared more
      active than VRP in reversing MDR, suggesting a possible role of this synthetic
      progestin as chemosensitizing agent in the clinical management of anthracycline
      resistant breast cancer.

PMID- 7645953
TI  - DNA-protein cell content of lymphokine activated killer (LAK) and target cells in
      coculture.
AB  - An extensive study of the interactions between LAK-target cells in cocultures was
      performed by means of cytometric (relative DNA and protein content) and
      morphological parameters. The aim was to obtain new information about the cell
      cycle stage of tumor target cells (Chang line) during the attack of LAK cells.
      Specimens obtained from cocultures at 0, 24, 48 hours were processed for electron
      microscopy, flow cytometry, immunocytochemistry (anti-BrdU reaction) and light
      microscopy (L.I., M.I., cell-cell interaction). The most intense activity of LAK
      cells against the target was found at 24 hours of coculture independently of the
      proliferative stage of the tumor cells. These results suggest that the high
      affinity between killer and target cells was not affected by the molecular
      changes of the Chang cell surface during the cell cycle.

PMID- 7645954
TI  - Differential (Ha-, K- and N-) ras p21 expression in benign and malignant human
      thyroid tumors: an immunohistochemical study.
AB  - An immunohistochemical study of 24 thyroid carcinomas, 10 thyroid adenomas and 10
      normal thyroids was performed using monoclonal antibodies directed against each
      of the three members of ras p21s; Ha-, K- and N-ras p21. Normal thyroids showed a
      negative staining for all of the three ras p21s. The expressional levels of the
      three ras p21s were various in each benign and malignant thyroid tumor, but a
      higher expression of Ha- and N-ras p21 and a lower or negative expression of K
      ras p21 was a common finding in thyroid tumors of all histologic categories.
      There were no correlations between the expressional levels of ras p21s and the
      histologic subtypes, tumor size or lymph node status in the thyroid carcinomas.

PMID- 7645955
TI  - Detection of O6-methylguanine-DNA methyltransferase-expression in human tumors by
      means of in situ hybridization.
AB  - The DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) is a main
      determinant of resistance of tumor cells towards nitrosoureas that are in use as
      cytostatic drugs. It therefore appears of importance to determine its expression
      in tumors before the utilization of nitrosoureas for tumor treatment. We have
      determined the level of expression of MGMT in mammary carcinomas and brain tumors
      by means of in situ hybridization, using digoxygenin-labeled RNA driven by MGMT
      expression vector in sense and antisense orientation. It is shown that the
      intensity of the hybridization signal correlates with the MGMT activity of a
      given tumor. The results demonstrate the applicability of in situ hybridization
      for determination of MGMT expression in tumor sections.

PMID- 7645956
TI  - Role of sodium pump systems to determine sensitivity to mitomycin C in non-small
      cell lung cancer cell lines.
AB  - There are some active transport systems in the cell membrane, such as potassium
      pump, calcium pump, and proton pump. Although it has been reported that
      sodium/potassium and sodium/calcium pumps of cell membrane play roles in the
      intracellular accumulation of anticancer agents, the significance of the active
      transport channels in accumulation of mitomycin C (MMC), one of the most active
      agents for non-small cell lung cancer (NSCLC) has been unclear. In this study, we
      evaluated the role of the potassium pump, calcium pump, and proton pump as
      determinants of the sensitivity to MMC in vitro by using the selective
      inhibitors, ouabain, verapamil or AG-2000 (an active metabolite of Lansoplazole),
      respectively. PC-9 and PC-9/MC4 cell lines which are sensitive and resistant to
      MMC were used for these experiments. PC-9/MC4 was 9.4-fold more resistant to MMC
      than PC-9 cells. Relative resistance was not significantly changed by co
      incubation with a non-cytotoxic dosage of these inhibitors. From these results,
      it was revealed that the active transport systems in cell membrane do not play a
      role in determining the sensitivity to MMC and the acquisition of resistance to
      MMC in PC-9 cell lines. Intracellular bioactivation may be an important factor to
      determine sensitivity to MMC in NSCLC cells under aerobic conditions.

PMID- 7645957
TI  - In vitro potentiation by lonidamine of the sc-RIP saporin 6 effect in a human
      metastatic breast cancer cell line.
AB  - The ability of Lonidamine (LND), an energolytic derivative of indazole-carboxylic
      acid, to modulate the antiproliferative effect of the single-chain ribosome
      inactivating protein Saporin 6 (SO 6) was investigated in the human MAST breast
      cancer cell line, recently established from an ascitic effusion of a ductal
      carcinoma, by analysis of protein synthesis inhibition and of colony formation in
      vitro. Different schedules were tested varying with regard to time of exposure (0
      24 h), concentration of the drugs (0.01- > 10 micrograms/ml SO 6; 25-100
      micrograms/ml LND) and sequence of administration (LND- > SO 6; SO 6- > LND; SO
      6+LND). Results indicate that the marginal activity exerted here by each drug
      when tested independently is highly potentiated by the combination treatments,
      the cytotoxicity becoming significantly greater than that expected from an
      additive effect between the two drugs. In particular, a strong synergistic effect
      is obtained when SO 6 preceedes LND, with a reduction of the SO 6 IC 50 from 1.3
      x 10(-7) M to 2.6 x 10(-9) M.

PMID- 7645958
TI  - Cisplatin induces apoptosis in SH-SY5Y human neuroblastoma cell line.
AB  - BACKGROUND: Cisplatin (CDDP) is cytotoxic, inducing apoptosis in some tumoral
      cell lines in vitro. Since CDDP is an effective drug in vivo treatment of
      neuroblastoma, we tested this drug on the human neuroblastoma SH-SY5Y cell line.
      Materials and methods. The effect of CDDP on cultured SH-SY5Y cells was
      determined with trypan blue dye exclusion test, LDH activity and DNA
      electrophoresis. Cultures were observed by light and electron microscope. Flow
      cytometric analysis was also carried out. RESULTS: CDDP inhibits the growth of
      neuroblastoma cells and reduces cell viability. Cell death occurs by apoptosis,
      as evidenced by morphological criteria and typical DNA laddering. Flow cytometry
      demonstrates that CDDP-treated cells are arrested in the G2/M phase before
      entering programmed cell death. CONCLUSIONS: CDDP is thus effective on the human
      neuroblastoma SH-SY5Y cell line, inducing apoptosis.

PMID- 7645959
TI  - "Seed" to "soil" is a return trip in metastasis.
AB  - A critical aspect in understanding and treating cancer progression and metastasis
      is the relationship of the host originating organ and metastatic "soil" organs
      that support the growth and progression of the cancer "seed". We have recently
      demonstrated that there is a great difference in seemingly similar visceral
      organs, the colon and the stomach to support the growth progression of
      transplanted human colon tumors in nude mice. To further understand the
      relationship of seed and soil in cancer, we transplanted the metastatic human
      colon tumor CO-3 on the liver of nude mice, which is a usual metastatic soil
      organ for this tumor if transplanted to the nude-mouse colon. The
      intrahepatically-transplanted CO-3 tumor grew extensively on the nude-mouse liver
      without intra-hepatic metastasis. However, cecal growth, peritoneal
      dissemination, and invasiveness were noted after extensive growth on the liver
      with no spread to other organs. This phenomenon suggested that the intra
      hepatically transplanted tumor could "reversibly metastasize" to the orthotopic
      site and secondarily spread into the abdominal cavity. The observation reported
      here suggests that "seed" to "soil" is reversible in metastasis in that the tumor
      can spread in either direction between two "matched" organ "soil".

PMID- 7645960
TI  - Cancer seed and soil can be highly selective: human-patient colon tumor lung
      metastasis grows in nude mouse lung but not colon or subcutis.
AB  - The question remains as to whether metastatic cells (cancer seed) that eventually
      colonize a particular organ (cancer soil) have specific properties that
      distinguish them from the other cells of the primary tumor. However until
      recently there have not been model systems in which this question could be fully
      answered. To further understand the relationship between seed and soil we have
      developed an orthotopic-transplantation nude-mouse model that allows human tumors
      to essentially replicate their behavior they had in the patient. The patient-like
      behavior of the transplanted human tumor in the nude mouse depends on the use of
      intact tumor tissue for orthotopic transplantation. Here we report that a
      colorectal tumor lung metastasis surgically resected from a patient could grow in
      nude mouse lung, but not in either the colon or the subcutis after
      transplantation of intact tissue. The results were striking in that the human
      colorectal tumor lung metastasis grew in the lung of the animals and not in the
      colon or in the subcutis of the animals. The results described here suggest that
      the lung metastasis of the patient colon tumor is distinct in its soil
      requirement from the majority of the cells of the original colon tumor. In
      contract, in the intact-tissue orthotopic transplant model, primary human colon
      tumors grow when transplanted to the colon of the nude mouse. Thus the colorectal
      cancer "seed" which metastasized to the lung in the patients seems very selective
      for the "soil" of the lung of both the patient and the nude mouse.

PMID- 7645961
TI  - Non-T cell disturbance causes the suppression of the autologous mixed lymphocyte
      reaction in patients with gastric carcinoma.
AB  - We investigated the accessory function of non-T cells to autoreactive T cells in
      autologous mixed lymphocyte reaction (AMLR) and clarified the cause of the
      suppression of autoreactivity in patients with gastric carcinoma. The response of
      T cells in the AMLR in gastric cancer patients was significantly suppressed
      compared with that in controls. In patients in whom the AMLR of the spleen was
      suppressed more than that of the peripheral blood, the degree of stimulation of
      non-T cells from the spleen was remarkably suppressed, on the other hand, in
      patients in whom AMLR of the peripheral blood was suppressed more than the
      spleen, the degree of stimulation from the peripheral blood was remarkably
      suppressed. The expression of HLA-DR antigens on non-T cells of gastric cancer
      patients was lower than that of controls. AMLR was considerably decreased in
      controls by the treatment non-T cells with anti-HLA-DR MoAb, but not in cancer
      patients. Treatment of non-T cells from the spleen of gastric cancer patients
      with IFN-gamma remarkably improved T cell proliferation in the AMLR. IFN-gamma
      also enhanced the expression of HLA-DR antigens on non-T cells. The disturbance
      of non-T cells was not biased to a specific population. These disturbances of non
      T cells suppressed the AMLR independently of stage status. Therefore, the
      immunological abnormality of non-T cells manifested by reduced accessory function
      to autoreactive T cells may cause impaired immunological surveillance against
      tumors and permit cancer cell growth.

PMID- 7645962
TI  - Relative efficacy of glucarate on the initiation and promotion phases of rat
      mammary carcinogenesis.
AB  - The independent effects of the potential cancer chemopreventive agent calcium
      glucarate (CGT) when fed (128 mmol/kg diet) during the initiation (I), promotion
      (P) or (I+P) phases of 7,12-dimethylbenzanthracene-induced rat mammary
      carcinogenesis, was compared to that of the known chemopreventive agent N-(4
      hydroxyphenyl) retinamide (4-HPR) fed (2.0 mmol/kg diet) during these same
      phases. CGT and especially 4-HPR both significantly increased tumor latency when
      fed during the P-phase. When fed during I, P or I+P phases mammary tumor
      incidence was reduced compared to the controls 33%, 42% and 67% by 4-HPR and 18%,
      42% and 50% by CGT. Similarly, tumor multiplicity was significantly reduced by
      either agent. For example, as compared to the corresponding control, when fed
      during the I, P or I+P phases 4-HPR reduced tumor multiplicity 63, 34 and 63%,
      while CGT reduced tumor multiplicity 28, 42 and 63% respectively. CGT, like 4
      HPR, acts on both the I and P phases with the effect being maximal when fed
      during P and I+P phases.

PMID- 7645963
TI  - RS-33295-198: a novel, potent modulator of P-glycoprotein-mediated multidrug
      resistance.
AB  - A novel multidrug resistance modulator, RS-33295-198, circumvented drug
      resistance in human, mouse, and Chinese hamster cell lines overexpressing P
      glycoprotein. It enhanced the antiproliferative activity of doxorubicin,
      vincristine, etoposide, and paclitaxel and increased doxorubicin retention in
      multidrug-resistant hamster CHRC5 cells. RS-33295-198 modulated doxorubicin
      resistance in a murine P388/ADR leukemia model when administered ip via
      continuous minipump delivery, ip by bolus injection, and orally; it also improved
      the efficacy of vincristine toward P388/VCR leukemia when given ip or po. RS
      33295-198 showed weak activity in enhancing doxorubicin efficacy against a
      multidrug-resistant human sarcoma xenograft.

PMID- 7645964
TI  - Heterogeneity in p53 mutations in mouse mammary tumor subpopulations with
      different metastatic potential from the orthotopic site.
AB  - We have found that p53 expression is altered with progression to the metastatic
      phenotype of a series of neoplastic subpopulations of a single mouse mammary
      tumor. Single strand conformation polymorphism (SSCP) analysis of p53 transcripts
      indicate that the expressed p53 genes in each of the subpopulations contain one
      or more differences from wild type p53. Although the mutations in the coding
      sequence of p53 are different in each of the sublines, suggesting that
      independent mutational events have occurred, the mutations are clustered in exons
      2-4 and in exon 6. In the metastatic subpopulations, there is either a complete
      loss of p53 transcriptional activity or accumulation of transcripts with an
      additional alteration in exons 4-5.

PMID- 7645965
TI  - Relationship between the cell-proliferative activity of gastric cancers and that
      of the normal epithelium.
AB  - Samples of gastric carcinomas and of normal gastric mucosa adjacent to tumors
      from 104 patients with primary mucosal gastric cancer were analysed by flow
      cytometry. These patients were divided into two groups according to the
      histologic type of their tumors (differentiated group and undifferentiated
      group). The pattern of DNA ploidy and the sizes of the S- and G2M-phase fractions
      (percentages of cells at each respective phase) were compared between these two
      groups. DNA aneuploidy was encountered in 25.4% of the cases in the
      differentiated group and in 21.2% of the cases in the undifferentiated group. The
      mean sizes of S- and G2M-phase fractions of carcinomas in the differentiated
      group were 8.85% and 3.75% and they were significantly higher than the mean sizes
      of S- and G2M-phase fractions of carcinomas in the undifferentiated group (6.97%
      and 2.92%). Moreover, the S-phase fraction of normal gastric mucosa adjacent to
      the differentiated adenocarcinoma was 5.75% and this value was significantly
      higher than that of normal gastric mucosa adjacent to undifferentiated
      adenocarcinoma (4.80%). These results suggest that the proliferative activity of
      mucosal gastric cancer cells, as described by flow-cytometry, is higher in cases
      of differentiated adenocarcinoma than in cases of undifferentiated
      adenocarcinoma, and that the proliferative activity of normal cells in the
      gastric mucosa close to where adenocarcinoma develops is higher in cases of
      differentiated adenocarcinoma than in cases of undifferentiated adenocarcinoma.
      Thus, differentiated adenocarcinoma seems to develop from gastric mucosa with
      high proliferative activity.

PMID- 7645966
TI  - Potential antitumor agent: steroidal bilactam ester of p-N, N-bis (2-chloroethyl)
      aminophenylacetic acid.
AB  - 7 alpha-, 17 alpha-Diaza-7, 17-dioxo-B, D-dihomo-5-androsten 3 beta-p-N, N-bis (2
      chloroethyl)aminophenylacetate, a modified steroidal alkylating agent, is active
      in the treatment of P388 and L1210 leukemias in vivo. The compound was also
      tested in vitro against L1210 and P388 leukemias, on DNA, RNA and protein
      synthesis and showed high inhibition effect. Also increases the frequency of
      Sister Chromatid Exchanges and reduces the replication index of human
      lymphocytes.

PMID- 7645967
TI  - Inhibitory effect of caffeine on potentially lethal damage repair in cisplatin
      treated human osteosarcoma cells.
AB  - Human osteosarcoma cells, that were cultured to confluence and maintained under
      low nutrient conditions, showed potentially lethal damage repair after cisplatin
      treatment. This repair was inhibited by a non-toxic dose of caffeine. Flow
      cytometric analysis indicated that cisplatin-treated cells accumulated in the S
      phase by 24 hr, followed by accumulation in the G2/M phase. Caffeine inhibited
      the initial accumulation in the S phase and the release of cells from the G2/M
      block. DNA synthesis was also inhibited by the cisplatin treatment. The addition
      of caffeine significantly reversed this inhibition. The content of DNA-bound
      platinum decreased over time after cisplatin treatment. Caffeine did not
      influence platinum content, nor did it directly affect the DNA excision repair.
      Cisplatin inhibits DNA synthesis in the S phase, but caffeine reduces this
      inhibition. Caffeine-treated cells that pass through S phase are incapable of
      recovery.

PMID- 7645968
TI  - Trial of a new medium-term model using benzo(a)pyrene induced lung tumor in
      newborn mice.
AB  - A new medium-term in vivo model was tried using pulmonary adenoma induced by
      benzo(a)pyrene (BP) in newborn mice. Both inbred mice such as C57BL/5J,
      C57BR/cdJ. A/J mice and non inbred N:GP(S) mice were used. Benzo(a)pyrene was
      injected in the subscapular region of newborn mice within 24 hours after birth at
      a dose of 0.5 mg and 1 mg per mouse, respectively. After 9 weeks lung tumor
      induced in N:GP(S) and A/J mice but in the other mice. The dose showing a 50%
      tumor incidence was found in N:GP(S) mice to be 0.5 mg of BP but the tumor
      incidence was very high in A/J mice even at 40 micrograms of BP, the lowest dose
      in this experiment. To verify the utility of this model, ascorbic acid, carrot,
      beta carotene, soybean lecithin, spinach, Sesamum indicum, Ganoderma lucidum,
      caffeine, red ginseng extract, fresh ginseng and 13-cis retinoic acid, some of
      which are known to have anticarcinogenic activity in various animal models, were
      tried with this system. Ascorbic acid, soybean lecithin, Ganoderma lucidum,
      caffeine and red ginseng extract showed inhibition of lung tumor incidence, while
      fresh ginseng, carrot, beta carotene, spinach and 13-cis retinoic acid did not.
      This result suggested that the 9-week medium-term model using lung tumor induced
      by 0.5 mg of BP was useful for the screening of cancer preventive agents.

PMID- 7645969
TI  - In vitro cytotoxicity and differential cellular sensitivity of derivatives of
      diamino acids. I. N1-methyl, N1-allyl, N1-(2-chloroethyl) and N1-propargyl ureas.
AB  - The in vitro cytotoxicity and differential cellular sensitivity of a series of
      new N1-methyl, N1-allyl, N1-2-chloroethyl and N1-propargyl urea derivatives of
      diamino acids were determined in the National Cancer Institute's primary
      antitumor drug screen. The compounds tested showed an in vitro anticancer
      activity similar to commercialized nitrosoureas such as CCNU, BCNU, MeCCNU,
      chlorozotocin, streptozotocin and PCNU. The alkylating moiety of the ureas seems
      to play a role in the general selectivity of our compounds. The N1-methyl and N1
      2-chloroethyl urea derivatives are more selective for central nervous system cell
      lines and the N1-allyl urea derivatives are more selective for lung cancer cell
      lines. The N1-propargyl ureas did not show any particular selectivity in the 60
      human cell lines tested.

PMID- 7645970
TI  - In vitro cytotoxicity and differential cellular sensitivity of derivatives of
      diamino acids. II. N1-methyl, N1-allyl, N1-(2-chloroethyl) and N1-propargyl
      nitrosoureas.
AB  - The in vitro cytotoxicity and differential cellular sensitivity of a series of
      new N1-methyl, N1-allyl, N1-2-chloroethyl and N1-propargyl nitrosourea
      derivatives of diamino acids were determined in the National Cancer Institute's
      primary antitumor drug screen. The compounds tested showed an in vitro anticancer
      activity similar to commercialized nitrosoureas such as CCNU, BCNU, MeCCNU,
      chlorozotocin, streptozotocin and PCNU. The alkylating moiety of the nitrosoureas
      seems to play a role in the general selectivity of our compounds. The N1-methyl
      and N1-2-chloroethyl nitrosourea derivatives are more selective for central
      nervous system cell lines, the N1-allyl nitrosourea derivatives are more
      selective for lung cancer cell lines and the N1-propargyl nitrosoureas are more
      selective for leukemia cell lines.

PMID- 7645971
TI  - Analysis of ras gene mutations in hepatocellular carcinoma in southern African
      blacks.
AB  - Paired samples of hepatocellular carcinoma and non-tumorous liver tissue from 12
      southern African blacks were examined for mutations in codons 12, 13, and 61 of
      the three ras proto-oncogenes (H-, K-, and N-ras). Deoxyribonucleic acid was
      isolated from carcinoma and non-tumorous tissues and amplified with the
      polymerase chain reaction. Using the single-stranded conformational polymorphisms
      method, products of the polymerase chain reaction amplification of codons 12, 13,
      and 61 of H-, K-, and N-ras were analysed for mutations. Mobility shifts were not
      detected except in one tumour in the region of codon 61 of K-ras. By sequencing
      the relevant polymerase chain reaction products, this sequence of
      deoxyribonucleic acid was proved to be normal, indicating that the single
      stranded conformational polymorphisms result was an artifact of the polymerase
      chain reaction. Thus, no mutations were detected in the regions of interest in
      any of the tumours studied. These results indicate that activation of ras proto
      oncogenes by mutations in codons 12, 13, and 61 does not play an important role
      in hepatocellular carcinogenesis in southern African Blacks despite the fact that
      dietary exposure to aflatoxin B1 is a risk factor in this population.

PMID- 7645972
TI  - Addition of hTNF alpha potentiates cytotoxicity of taxol in human ovarian cancer
      lines.
AB  - Some reports indicate that the cytotoxic activity of hTNFa and taxol might be
      enhanced when combined with certain chemotherapeutic agents. To assess if taxol
      might modulate the action of hTNF alpha, we have studied the cytotoxic action of
      hTNF alpha in combination with taxol on two ovarian carcinoma cell lines, the
      SKOV3 and SKVLB. These two cell lines are resistant to the action of hTNF alpha.
      The SKVLB cells overexpressed the multidrug resistant gene (MDR-1) which confers
      a resistance to taxol. We observed that the combination of low concentration of
      hTNF alpha with taxol could increase the cytotoxic activity of taxol in SKOV3
      cells. Furthermore, a four-hour pretreatment with taxol before adding hTNF alpha
      to the culture has shown a significant increase in their cytotoxic activity. This
      increase was not observed at the same level in SKOV3 cells pretreated with hTNF
      alpha. However, the phenomena was not observed in SKVLB cells. This indicates
      that taxol could alter the mechanism of hTNF alpha-resistance.

PMID- 7645974
TI  - In vitro and in vivo studies on the anticancer activity of dehydroilludin M.
AB  - Six first-generation illudin analogs were tested for antitumor activity using in
      vitro cytotoxicity and in vivo xenograft models. One analog, dehydroilludin M,
      inhibited xenograft growth and prolonged life span of tumor bearing animals, when
      administered IP or IV, whereas the parent Illudin S compound was ineffective. The
      efficacy of dehydroilludin M in the MV522 lung carcinoma model exceeded that of 9
      known anticancer drugs, and equaled that of mitomycin C. Dehydroilludin M
      retained the in vitro relative selective cytotoxicity for carcinomas and myeloid
      leukemia cell lines noted with the parent illudin compounds. In vitro
      cytotoxicity data predicted response of xenografts. Dehydroilludin M also
      retained the in vitro activity of the parent compounds against different
      multidrug resistant mdr cell lines.

PMID- 7645973
TI  - Nonresponsiveness of the metastatic human lung carcinoma MV522 xenograft to
      conventional anticancer agents.
AB  - The human lung carcinoma cell line MV522 was previously noted to produce
      extensive metastasis to the lungs, spleen and lymph nodes after subcutaneous
      transplantation into athymic nude mice. Animals eventually succumb to these
      metastases, and not primary tumor growth. The ability to produce extensive
      metastasis after a simple subcutaneous injection in 100% of animals (> 100 tested
      to date) would be an advantage when screening compounds for anticancer activity.
      To validate the utility of this xenograft model for testing anticancer agents, we
      tested the ability of 10 anticancer drugs to either inhibit primary tumor growth
      and/or prolong life span of MV522-bearing animals. Among the 10 antitumor
      conventional agents, only mitomycin C and taxol demonstrated primary tumor growth
      inhibition. Mitomycin C produced a mild increase in median life span of 41% to
      63%, while taxol had inconsistent effects. The metastatic MV522 carcinoma model
      appears to reflect clinical resistance of primary non-small cell lung cancer to
      conventional chemotherapeutic agents and should be useful for testing new anti
      cancer drugs.

PMID- 7645975
TI  - Discordant effects of butyrate analogues on erythroleukemia cell proliferation,
      differentiation and histone deacetylase.
AB  - Actions of butyrate and structural analogues on histone deacetylase activity were
      compared with effects on proliferation and differentiation of erythroleukemia
      cells. Proliferation was inhibited by 5 mM tert- butylacetate, phenylacetate,
      phenylbutyrate, 3-bromopropionate and ethyl butyrate without induction of
      hemoglobin synthesis. n - Butyramide was a stronger inhibitor of cell
      proliferation and a more effective inducer of hemoglobin synthesis than
      isobutyramide. The data from combination studies were compatible with butyramide
      and isobutyramide being weaker agonists that competed for a common site with
      butyrate. Butyramide and isobutyramide were weaker inhibitors of histone
      deacetylase than 4-phenylbutyrate and phenylacetate, which in turn were less
      effective than 3-bromopropionate and butyrate. Butyrate and analogues had similar
      inhibitory effects on histone deacetylase activity in nuclei from mouse DS19
      cells and human K562 cells. Effects on histone deacetylase did not show a
      consistent correlation with inhibition of cell proliferation or induction of
      hemoglobin synthesis.

PMID- 7645976
TI  - Significance of P-53 antigen in malignant melanomas and naevi of the head and
      neck area.
AB  - DO-7 antibody against p-53 antigen was applied for investigation of melanomas of
      facial skin (25 cases), oral cavity (17 cases), eye (18 cases) and naevi (25
      cases). The p-53 index value (% of p-53 positive cells) was correlated with the
      thickness of the tumour, the presence of metastases and survival time. The
      difference in p-53 index between naevi and melanomas was statistically
      significant (p < < 0.01). A significant correlation was found between the p-53
      index value and the thickness of the tumour, the presence of metastases and
      follow-up for patients with skin, oral and ocular melanomas. The possible
      diagnostic and prognostic significance of p-53 antigen in melanomas and naevi of
      the head and neck area is discussed.

PMID- 7645977
TI  - Transcription factors: structure, function, and implication in malignant growth.
AB  - Transcription factors are the principal modulators of gene expression patterns in
      the organism and are thus involved in processes leading to changes in
      developmental programmes, responses to growth and differentiation signals, and
      some of the alterations causing neoplastic transformation. The present overview
      deals with general aspects of the structure, function, and regulation of
      transcription factors, in relation to their physiological role and oncogenic
      potential.

PMID- 7645978
TI  - Chemical and biological properties of a new cis-diammineplatinum (II) complex
      containing para-aminobenzoic acid as amino ligand.
AB  - In this paper we report on the synthesis, characterization and preliminary
      pharmacological evaluation of a new platinum (II) complex obtained by reaction of
      cis-diamminedichloroplatinum(II) (DDP) with para-aminobenzoic acid (PABA). The
      structure of this platinum compound was defined by UV, IR, 1H-NMR and elemental
      analysis. DPAB tested in vitro and in vivo against P388 leukemic cells displayed
      good antiproliferative (IC50 values after 48 h exposure of cells = 3
      micrograms/ml) and antitumor activity (T/C% = 150). This compound also possesses
      desirable physical properties, such as a good solubility and stability in aqueous
      media, and a low toxicity (LD50 > 1200 mg/kg body weight) combined with a
      moderate nephrotoxic activity [plasma urea nitrogen (PUN) level: 36 +/- 8(SD)
      mg/100 ml]. DPAB was cleared from plasma ultrafiltrate (UF-plasma) very rapidly
      [clearance (CL), 55.3 ml x min-1 x kg-1], showing a half-life of 13.6 min.
      Platinum exposure (AUC) in the kidney was 2.6 times greater than that found in UF
      plasma. AUCS for liver, stomach and UF-plasma were similar, while the AUC value
      for the spleen was 1.7 times lower than that of UF-plasma. These preliminary
      results seem to hold interest for further preclinical evaluation of the
      biological activity of this new platinum compound.

PMID- 7645979
TI  - Thymidylate synthase level and DNA-ploidy pattern as possible prognostic factors
      in human colorectal cancer: a preliminary study.
AB  - 5-Fluorouracil is the drug chosen for the treatment of patients with advanced
      colorectal carcinoma; its major site of action is thymidylate synthase (TS),
      resulting in pronounced and prolonged inhibition of DNA synthesis. The aim of
      this study was to evaluate the possibility of considering TS level in human
      colorectal carcinomas of previously untreated patients (pts) as a prognostic
      factor. Our data demonstrate that there is no association with age, sex, tumor
      site and tumor size; however, there is a relationship between TS levels and
      staging: in fact, the TS values are higher (P < 0.05) in Dukes-A tumors than in
      the others. A significant association was also found between the TS levels and
      survival parameters: in fact, pts with longer disease-free and overall survivals
      had a significantly increased TS level compared to pts with a poorer outcome (P <
      0.05). Moreover, pts with DNA-aneuploid tumors had lower TS level (median = 0.044
      pmol/mg protein) than diploid pts who had higher TS level (median = 0.093 pmol/mg
      protein); however the difference is not significant. Our result are based on
      preliminary data; however, they seem to support the hypothesis that a high TS
      level is a favourable prognostic factor in human colorectal carcinoma.

PMID- 7645980
TI  - Methylglyoxal bis (cyclopentylamidinohydrazone) (MGBCP): antitumor effect against
      human osteosarcoma cells and combined effect with methotrexate, adriamycin and 4
      hydroperoxyifosfamide.
AB  - The antitumor effect of a polyamine biosynthetic pathway inhibitor methylglyoxal
      bis(cyclopentylamidinohydrazone) (MGBCP) on human osteosarcoma cell lines such as
      KHOS-240S, MG-63 and G-292 cells, and its effect in combination with anticancer
      drugs such as methotrexate (MTX), adriamycin (ADM) and 4-hydroperoxyfosfamide
      (HIFO) have been investigated. The growth of these cultured osteosarcoma cells
      was inhibited by MGBCP in a dose-dependent manner. Spermidine and spermine levels
      were dose-dependently depressed in these MGBCP-treated osteosarcoma cells. The
      antitumor effect of MGBCP was additively potentiated by combined treatment with
      MTX, ADM and HIFO, respectively.

PMID- 7645981
TI  - Modulation of doxorubicin resistance in P388/ADR cells by Ro44-5912, a tiapamil
      derivative.
AB  - We describe here investigations into the ability of a tiapamil derivative, Ro44
      5912 to overcome multidrug resistance (MDR) in doxorubicin (ADR)-resistant murine
      leukemic P388 cells. This compound has the formula: C27H39NO4S2.1:2C6H8O6, a M.
      W. of 858 and is structurally similar to verapamil, an established inhibitor of P
      glycoprotein (PGP). We have compared the MDR modulating properties of Ro44-5912
      with verapamil in P388ADR cells. Doxorubicin concentration required to achieve
      50% inhibition of growth (IC50) for P388ADR cells was found to be 24 microM. In
      contrast, treatment of P388ADR cells with Doxorubicin and 3 microM verapamil
      decreased the IC50 value to 2.5 microM. A further decrease was observed with 3
      microM Ro44-5912 treatment, where an IC50 value of 1.1 microM was obtained.
      Doxorubicin accumulation was also determined by flow cytometry in order to
      determine whether the increased levels of chemosensitivity observed for Ro44-5912
      were reflected by increased cellular drug uptake. The results revealed that Ro44
      5912, at equivalent concentration, increased doxorubicin accumulation in P388ADR
      cells beyond that obtained with verapamil whereas no effects were seen with the
      parental P388 cells. The effect of Ro44-5912 on the binding of C219 monoclonal
      antibody to PGP in MDR cells was also studied and found not to decrease C219
      expression on P388ADR cells.

PMID- 7645983
TI  - Modulation by canine interferon-gamma of major histocompatibility complex and
      tumor-associated antigen expression in canine mammary tumor and melanoma cell
      lines.
AB  - In an effort to enhance the antigenicity of canine tumor cells, canine interferon
      gamma (CnIFN-gamma) was applied in vitro to seven canine mammary tumor (CMT) and
      two canine melanoma (CML) cell lines. Surface expression of major
      histocompatibility complex (MHC) antigens and tumor-associated antigens (TAA) was
      measured by a flow cytometric fluorescence assay using commercially available
      anti-MHC antibodies, and anti-canine TAA monoclonal antibodies generated against
      CMT and CML cell lines. Compared to constitutive antigen levels in untreated
      cells, treatment with CnIFN-gamma resulted in increased expression of MHC class I
      and II antigens (up to 19- and 167-fold, respectively) and a TAA (up to 5-fold)
      by CMT cell lines, and increased expression of class I antigen (131-fold) by one
      CML and of class II antigen (18-fold) by the other CML cell line. Expression of
      MHC antigens and a TAA by tumor cells was increased by Cn-IFN-gamma treatment,
      and such an increase may be of potential benefit in tumor cell recognition and
      rejection by the immune system.

PMID- 7645982
TI  - Hypochlorite scavenging activity of polyphenols.
AB  - Chemiluminescence, generated by the mixture of sodium hypochlorite solution and
      luminol, was completely eliminated by polyphenols, such as natural lignins,
      phenylpropenoid monomers and polymers, and epigallocatechin gallate. On the other
      hand, hypochlorite scavenging activity of polysaccharides, such as PSK (Krestin)
      and Schizophyllan, was relatively weak. Human myelogenous leukemic cell lines (HL
      60, ML-1) showed higher production of active oxygen(s) (detected by luminol
      chemiluminescence) and iodination capacity, than six other cultured cell lines.
      Since lignin did not completely eliminate the active oxygen production by HL-60
      cells, possible stimulation of hypochlorite production by lignin was suggested.

PMID- 7645984
TI  - Immunohistochemical phenotyping and PCNA detection in gastrointestinal stromal
      tumors.
AB  - The immunohistochemical profile and the expression of proliferating cell nuclear
      antigen (PCNA) were studied in a series of 44 mesenchymal tumors of the
      gastrointestinal tract (GIT). On routinely hematoxylin-eosin stained sections 31
      cases were classified as leiomyomas or leiomyomatoid tumors, 12 as
      leiomyosarcomas and 1 as a neurilemmoma. Immunohistochemical stains for smooth
      muscle antigen (SMA), S-100 protein, glial fibrillary acidic protein (GFAP),
      vimentin and desmin were performed with the peroxidase-antiperoxidase method on
      paraffin sections. The streptavidin-biotin method for PCNA immunostaining was
      applied using the monoclonal antibody PC 10. On the basis of immunohistochemical
      findings, 32 cases were identified as leiomyomatoid tumors or leiomyosarcomas
      (SMA positive, S-100 protein negative), 2 cases as nerve sheath tumors (SMA
      negative, S-100 protein and GFAP positive), whereas 8 cases presented a mixed
      phenotype (SMA positive and S-100 protein positive). Two cases were negative for
      both SMA and S-100 protein. All tumors showed positive immunostaining for
      vimentin and a negative one for desmin. There was a correlation between the
      histologic grade and proliferating score, displayed by PCNA expression in tumors
      of smooth muscle origin. The PCNA expression in tumors of mixed phenotype was
      intermediate to that seen in leiomyosarcomas (high expression) and in leiomyomas
      (low expression).

PMID- 7645986
TI  - Expression of c-myc proteins in breast cancer as related to established
      prognostic factors and survival.
AB  - The expression of c-myc proteins was analysed immunohistochemically in a series
      of 206 breast carcinomas with special focus on established prognostic factors and
      patient survival. Nuclear expression of c-myc proteins was detected in 12% of
      carcinomas, and it was related to the lack of estrogen receptors (p = 0.05).
      Cytoplasmic expression of c-myc was present in 95% of the tumours. Expression of
      cytoplasmic c-myc at the invasive margin was related to tumour grade (p =
      0.0013), low mitotic index (p = 0.0002) and low S phase fraction (p = 0.026), and
      weakly associated with distant metastasis at diagnosis (p = 0.06) and to a high
      proportion of intraductal growth (p = 0.08). Long recurrence-free survival of the
      patients was related to strong cytoplasmic expression of c-myc at the invasive
      margin in the entire series (p = 0.0049) and in axillary lymph node-negative
      (ANN) (p = 0.0028) tumours. Cytoplasmic c-myc expression in the central areas of
      the tumour predicted metastasis at diagnosis (p = 0.002), non-ductal type of
      growth (p = 0.018) and low mitotic index (p = 0.005). Expression of c-myc in the
      stroma was related to the lack of estrogen receptors (p = 0.02) and to high S
      phase fraction (p = 0.01). The results show that overexpression of c-myc is
      involved in a highly complex manner with the early stages of breast cancer
      development, but it shows hardly any independent prognostic value over standard
      prognostic factors in clinical disease.

PMID- 7645985
TI  - The cytotoxicity of 3'-aminocyanoborane-2', 3'-dideoxypyrimidines in murine and
      human tissue cultured cell lines.
AB  - 3'-Aminocyanoborane-2', 3'-dideoxythymidine (VIIa) and 3'-aminocyanoborane-2', 3'
      dideoxyuridine (VIIIb) were successfully synthesized. The thymidine derivative
      (VIIIa) was shown to be a potent cytotoxic agent in murine and selected human
      suspended and solid tumor cell lines. Compound VIIIa inhibited L-1210 leukemia
      DNA and RNA synthesis with the protein synthesis requiring a higher concentration
      of drug for inhibition within 60 min. The purine pathway appeared to be the major
      target of Compound VIIIa with inhibition of IMP dehydrogenase and dihydrofolate
      reductase activities. The compound affected metabolic enzyme activities in the
      pyrimidine pathway as well as the nucleoside kinase activities. The DNA molecule
      did not appear to be target of the 3'-aminocyanoborane-2', 3'-dideoxythymidine
      (VIIIa), in that there was no change in ct-DNA viscosity, thermal denaturation or
      absorption of nucleosides of DNA nor was there any L-1210 DNA strand scission or
      inhibition of L-1210 DNA topoisomerase II activity when compound VIIIa was
      incubated at 100 microM.

PMID- 7645987
TI  - Human papillomavirus infection in esophageal squamous cell papillomas: a study of
      29 lesions.
AB  - The etiology and pathogenesis of esophageal squamous cell papillomas (ESCP), rare
      benign tumors of human esophagus, are still controversial. Chronic mucosal
      irritation and infection with human papillomaviruses (HPV) are two proposed
      etiologies. To investigate these hypotheses, we screened 29 ESCPs from 28
      patients originating from Slovenia and Poland for HPV infection using in situ
      hybridization (ISH) and polymerase chain reaction (PCR). No evidence of HPV DNA
      was found using ISH. By PCR, the presence of HPV DNA was detected in only one
      lesion using two different HPV L1 consensus primer sets. The restriction fragment
      analyses of PCR product showed patterns unique to HPV type 6. All other ESCPs
      were successfully amplified only with internal control human beta-globin primers.
      Our results show that HPV DNA is not frequently detectable in ESCPs, even when
      highly sensitive methods like PCR are used and that other pathogenetic mechanisms
      are more important in the etiology of ESCPs.

PMID- 7645988
TI  - Stimulation by epigallocatechin gallate of interleukin-1 production by human
      peripheral blood mononuclear cells.
AB  - (-) Epigallocatechin gallate (EGCg) potently stimulated the production of
      interleukin-1 (IL-1) and tumor necrosis factor by human peripheral blood
      mononuclear cells. The intracellular amounts of IL-1 beta and especially IL-1
      alpha induced by EGCg, were significantly higher than their extracellular
      counterparts. ECCg stimulated the production of adherent cells, with IL-1
      producing capacity (per cell basis) that was significantly higher than
      nonadherent cells. Although IL-1 alpha mRNA synthesis (assessed by Reverse
      Transcriptase-Polymerase Chain Reaction) was slightly enhanced, IL-1 beta mRNA
      synthesis was not significantly enhanced by EGCg treatment. Lipopolysaccharide
      (LPS) also stimulated the production of IL-1 alpha and IL-1 beta production, but
      failed to induce the adherent cells. These data suggest that EGCg and LPS
      stimulate mononuclear cells by different mechanisms.

PMID- 7645989
TI  - Autoradiographic evaluation of radiolabeled monoclonal antibody B72.3
      distribution in tumor and lymph nodes of adenocarcinoma patients.
AB  - Monoclonal antibody B72.3 recognizes a pancarcinoma antigen termed TAG-72 and is
      the MAb in "OncoScint CR/OV". Patients undergoing surgical resection of primary
      or metastatic colorectal or breast carcinoma or pseudomyxoma peritonei were
      injected i.v. with 125I-labeled MAb B72.3. Autoradiography identified the tissue
      distribution of the injected radiolabeled MAb B72.3. Immunohistochemical staining
      identified the corresponding spatial distribution of the target antigen, TAG-72.
      The labeling pattern seen using autoradiography closely matched the pattern that
      was observed using immunohistochemical techniques. This was especially notable in
      the mucin-containing compartments of the different tumors. The 125I-B72.3 was
      also found associated with the neoplastic cells, demonstrating a good penetration
      and specificity of the radiopharmaceutical through the tumor masses. The regional
      lymph nodes examined were the only tissues in which autoradiography and
      immunoperoxidase gave different results. In these specimens, the presence of TAG
      72 antigen in the parafollicular area, as shown by immunoperoxidase, contrasted
      with the silver grain deposition, due to the 125I-B72.3, in germinal centers.
      These findings suggest differences in the clearance pathways of the TAG-72
      antigen and B72.3 MAb.

PMID- 7645990
TI  - Granulocytapheresis as a possible cancer treatment.
AB  - We assessed the effect of granulocyte apheresis in patients exhibiting increased
      granulocyte-to-lymphocyte ratio in order to overcome granulocytosis occurring in
      the terminal stages of malignancies. 17 patients with post-operative recurrent
      metastatic tumors including 6 gastric, 3 colonic, 2 rectal, 1 esophageal and 5
      breast cancers were selected. The granulocytapheresis was performed by
      extracorporeal vein-to-vein circulation equipped with an apheresis column filled
      with cellulose acetate beads. Each week the patients underwent one or two
      sessions of treatment that lasted 30 to 50 minutes per session at a flow rate of
      30 to 50 ml/min. 15 sessions formed 1 therapeutic cycle. The effect of
      granulocytapheresis resulted in partial response (PR) in 4 cases, no change (NC)
      in 7 cases and partial disease (PD) in 6 cases. The performance status showed 30%
      remission. None of the patients exhibited significant side effects. Since the
      treatment demonstrated anti-tumor effects, granulocytapheresis may be applied
      during combined cancer treatments.

PMID- 7645991
TI  - Immunodetection of the presence or absence of full-length APC gene product in
      human colonic tissues.
AB  - In order to detect the presence or absence of wild-type adenomatous polyposis
      coli (APC) gene protein (APC) in human colonic tissues, we immunoaffinity
      purified two polyclonal rabbit antibodies (APC-1 and APC-2) directed against
      defined epitopes in the middle and carboxyl regions of APC. Such antibodies
      proved useful in western blot analysis of matched colonic mucosa and tumor sample
      pairs. A 300 kDa band corresponding to APC was detected in samples from normal
      colonic mucosa using both antibodies. No tumor samples (n = 14) showed a
      detectable 300 kDa band. SW480 colon carcinoma cells, known to express truncated
      APC lacking the carboxyl half of the protein, were also negative. These results
      indicate that our antibodies bind to full-length but not truncated APC. Thus,
      western blot analysis employing APC-1 and APC-2 antibodies may be used to
      evaluate the absence or presence of wild-type APC. The value of this methodology
      in detecting APC mutations, which mainly involve protein truncation or allelic
      loss, is based on its ability to demonstrate negative or reduced level of
      immunoreactivity toward full-length APC in tissues that contain such mutations.

PMID- 7645992
TI  - Sex steroid hormones and receptors in relation to S-phase fraction and ploidy
      level in endometrial carcinoma.
AB  - Although endogenous hormones exert an effect on the proliferation of endometria
      adenocarcinoma, there also seems to be an autonomous proliferation of the
      malignant cells. Simultaneous measurement of endocrine and cell proliferation
      related variables in endometrial adenocarcinoma specimens are expected to
      increase the understanding of factors responsible for progression or regression
      of this form of cancer. Sixty patients with endometrial adenocarcinoma were
      examined. The following parameters were analysed: endogenous plasma concentration
      of oestradiol, oestrone, progesterone, androstenedione and testosterone; S-phase
      fraction (SPF) and ploidy level, by flow cytometry; oestrogen and progesterone
      receptors, by immunohistochemistry. The oestrogen receptor positive tumours had a
      lower S-phase fraction that receptor negative tumours (p < 0.05), but SPF was
      still under the mean for the whole group. ER positive tumours were all diploid,
      while progesterone receptors were found also in aneuploid tumours. The presence
      of PR did not relate to lower SPF, but in an earlier study increased progesterone
      concentration was found to relate to lower SPF, and the antiproliferative effect
      of progesterone was also seen in more malignant tumours.

PMID- 7645993
TI  - Laparoscopic ureteral anti-reflux plasty reimplantation. First clinical
      experience.
AB  - Several animal studies have demonstrated that antireflux surgery by means of
      laparoscopy is technically feasible, but clinical experience is as yet lacking.
      Six girls aged between 6 and 10 years underwent laparoscopic Lich-Gregoir anti
      reflux surgery for vesicoureteral reflux and recurrent urinary infections. Three
      unilateral and three bilateral procedures were performed. No ureteral stents were
      used. One girl was operated on via an extraperitoneal approach. A mild unilateral
      stenosis was observed in one child, which, however, subsided after stenting for
      six weeks. A borderline compensated pyeloureteral stenosis decompensated shortly
      after the operation. Another child had an uncomplicated urinary tract infection.
      No other complications were seen. The laparoscopic Lich-Gregoir antireflux
      procedure is a complicated operation, which offers no advantage over the
      conventional procedure.

PMID- 7645994
TI  - Andrological laparoscopy.
AB  - The laparoscopic technique has well defined indications for some andrological
      procedures such as the diagnosis and the treatment of cryptorchidism, but its
      role remains controversial in varix ligation for which laparoscopy is however the
      newest development. At the Institute of Urology of the University of Milan from
      January 1992 to June 1994 five adults patients with undescended and unpalpable
      testis underwent laparoscopy. In 4 cases laparoscopic orchiopexy (2 direct and 2
      staged procedures) and in one case laparoscopic orchiectomy have been performed.
      In the same period 20 cases of varicocele (6 bilateral) have been observed and
      treated by laparoscopic varix ligation. For cryptorchidism after the
      identification of the testis we decide on the basis of parenchimal trophism
      wheter to perform orchidopexy or orchiectomy. A single step laparoscopic
      orchiopexy can be performed if the undescended testis is located proximal to the
      internal inguinal ring and if the mobilization of the spermatic vessels allows
      it. A Fowler-Stephens staged orchiopexy is indicated for intra abdominal testicle
      with short spermatic vessels. In the first stage the spermatic vessels are
      isolated and divided relying on the compensation offered by the deferential and
      extrafunicular vessels. After six months, once the testis trophism has been
      ascertained, the testis can be placed in the scrotum. For varicocelectomy the
      peritoneum is incised at the projection of the spermatic cord from the internal
      inguinal ring. A blunt and gentle dissection prepares the spermatic vascular
      bundle, the spermatic artery is identified and isolated and the vein are clipped
      and divided.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7645995
TI  - Experimental and clinical urinary diversion.
AB  - In order to achieve an appropriate technical experience and explore clinical
      feasibility of laparoscopic urinary diversion, the authors planned a laboratory
      experiment. In ten male pigs weighing about 25 kilograms cystoprostatectomy was
      performed. Ureterocutaneostomy or ureterosigmoidostomy were carried out next. For
      ureterocutaneostomy a channel was bluntly dissected through the abdominal wall.
      The ureter was grasped by a clamp passed through the stroma, drawn outside and
      anstomosed to the skin. Operative time was about 30 minutes. For
      ureterosigmoidostomy a longitudinal incision of approximately 1 cm was made
      through the wall of the sigmoid colon in order to reach the mucosa. A very small
      opening in the angle of the incision was made. A suture was placed in the
      ureteral tip and secured to the colon wall. Finally, the ureter was covered in
      its bed with antireflux technique. Operative time was about 180 minutes.
      Laparoscopic ureterocutaneostomy was also successfully applied in a compromised
      patient to resolve a particular clinical situation.

PMID- 7645996
TI  - The future of laparoscopy in urology.
AB  - Laparoscopy has not changed urological techniques as radically as could be
      supposed, as only 17% of urological techniques are performed by laparoscopy
      instead of the predicted 70%. However, this limited proportion corresponds to 30%
      of urological operating time. The author proposes a combination of open surgery
      and laparoscopy in certain cases. Laparoscopy is responsible for lower blood
      loss, less postoperative pain, a shorter hospital stay and a very small scar
      which account for its popularity among patients. A rational combination of
      laparoscopy, endoscopy and open surgery to treat urological diseases should be
      developed in the future.

PMID- 7645998
TI  - Urology.

PMID- 7645997
TI  - [Treatment of inguinal hernia using laparoscopy. Clinical experiences apropos of
      300 cases].
AB  - 300 laparoscopic treatments of inguinal hernia repair have be done in our
      hospital between may 1992 and juin 1994. 134 times we have seen a median hernia
      and 166 times a lateral one. In 44 patients (14%) we did the repair of hernia for
      bilateral disease. In 66 cases we underwent for recidive; 55 times after hernia
      repair by the Bassini technique or Shouldice technique, and only 8 times after
      laparoscopic repair. In 1.4% we have seen early recidivism, no more then in the
      classical technique. Of course philosophy of this technique is very different to
      the traditional repair of inguinal hernia, but the encouraging results, important
      decrease of pain after surgery and the early uptake of normal activity are the
      reasons why we use this technique for nearly all recidivism of hernia repair and
      even for a great number of important hernias.

PMID- 7645999
TI  - Laparoscopy of the kidney and the adrenal gland.
AB  - Diseases of the kidney and of the adrenal gland can be managed surgically by the
      laparoscopic approach. Laparoscopic nephrectomy, nephroureterectomy, renal cyst
      resection and adrenalectomy have been reported. This paper describes our early
      experience with the laparoscopic approach for the treatment of diseases of the
      kidney and of the adrenal gland. Since June we have performed 4 nephrectomies, 14
      renal cyst excisions and one adrenalectomy. Postoperative recovery and need for
      pain medication were reduced. Complications have been rare. At the present time
      laparoscopic nephrectomy for benign renal diseases, laparoscopic excision of
      recurrent renal cysts and laparoscopic adrenalectomy for functioning renal
      tumours should be considered. The role of laparoscopic approach for treatment of
      malignant diseases of the kidney and of the adrenal gland is still debatable.

PMID- 7646000
TI  - Ureteral laparoscopic surgery.
AB  - During the past years, laparoscopy has grown in popularity and become an
      alternative technique for the treatment of certain pathologies in urological
      practice. Retroperitoneal laparoscopic procedures for ureteral surgery were first
      attempted by Wickham in 1979: in this case a patient with a ureteral calculus
      underwent a successful ureterolithotomy; More recently, the introduction of the
      Gaur balloon has permitted quick dilatation and easier access to the
      retroperitoneum. However, in comparison, the transperitoneal method offers more
      space and better vision for identification of anatomical landmarks. In our
      clinic, we have performed laparoscopic ureteral surgery using the transperitoneal
      as well as the retroperitoneal approach. For situations requiring reconstructive
      surgery, we preferred the transperitoneal approach in 3 cases of ureterolysis; 2
      diagnostical and 1 therapeutical. On the other hand, the retroperitoneal approach
      was employed for carrying out 2 pyeloplasty, 1 ureterocutaneostomy and 1
      ureterolithotomy. Furthermore, we performed in similar fashion 3
      nephroureterectomy and 1 heminephrectomy combined with partial ureterectomy. In 3
      cases, transperitoneal nephroureterectomy with transurethral orifice circumcision
      was carried out. In all patients, laparoscopy revealed low morbidity with low
      grade postoperative pain and shorter hospital stay. Our experience shows that the
      progressive use of retroperitoneoscopic surgery can maintain minimal invasiveness
      and permit good access to various procedures without complications connected to
      use of the Veress needle or the presence of abdominal adhesions. In addition to
      our own laparoscopic experience, we have reviewed the literature and report on
      the most frequent ureteral surgery performed laparoscopically.

PMID- 7646001
TI  - Laparoscopic pelvic lymphadenectomy for prostatic cancer.
AB  - Development of laparoscopic techniques has converted lymphadenectomy into a real
      alternative to current laparotomy technique. The limitation of diagnostic imaging
      methods to know ganglion involvement in prostate cancer as well the high
      incidence of false negatives in frozen intrasurgical biopsies following open
      surgery lymphadenectomy has pushed us since november of 1990 to develop
      laparoscopic lymphadenectomy with staging. This study analyses the diverse
      diagnostic imaging methods and continues with a precise description of the
      laparoscopic technique. The authors summarize the results of our series and
      finish the article with a review of the most controversial aspects as well as the
      diagnostic value, advantages and disadvantages with respect to open surgery
      techniques, complications and indications of this technique at the present
      moment.

PMID- 7646002
TI  - Diagnostic laparoscopic retroperitoneal lymph node dissection for non
      seminomatous testicular tumor.
AB  - Retroperitoneal lymph node dissection for nonseminomatous testicular tumor. A
      modified retroperitoneal lymph node dissection for stage I testicular tumor has
      been described by Weissbach. We have developed a two-step procedure for
      performing laparoscopic retroperitoneal lymph-adenectomy within these boundaries.
      In the first step, a ventral approach is used. The colon is dissected free, then
      the spermatic vein is excised, and the borders of the dissection are defined.
      Removal of retroaortic and retrocaval nodal tissue is technically not feasible
      via the ventral approach. Therefore, in the second step, a lateral approach is
      employed, which is the key to success since it permits easy transection of the
      lumbar vessels. Thus complete lymph node dissection can be achieved. Between
      August 1992 and March 1994 this procedure was performed in 15 patients. In nine
      patients, the tumor was on the right side and in six on the left. Conversion to
      open surgery was necessary in two patients because of uncontrollable bleeding and
      a large metastasis, respectively. Microscopic metastases were detected in two
      other patients. Apart from the above-mentioned bleeding no major complications
      occurred; no blood transfusion were required. The results obtained so far
      demonstrate that this procedure is technically feasible. Therefore, we have
      decided to perform laparoscopic retroperitoneal lymphadenectomy also in patients
      with stage II B tumors who have received chemotherapy; to date one patient with a
      left-sided stage II B tumor has been operated on successfully.

PMID- 7646003
TI  - Retroperitoneoscopy.
AB  - From October 1992 to June 1994, 12 nephrectomies (all for benign diseases), one
      nephropexy and 7 adrenalectomies (one pheochromocitoma, three adenomas, one cyst)
      were performed. In all the cases the retroperitoneal working space was created
      with direct CO2 insufflation (without balloon) with the patient in prone
      position. Four 10-12 mm ports were always inserted in the lumbar area. Eighteen
      procedures were successful (90%), 2 failed (one nephrectomy and one
      adrenalectomy) and underwent open surgery. Twelve procedures were carried out
      with the patients in prone position, six (one nephropexy and 5 nephrectomies)
      were performed with the patients in lateral de cubitus. The removal of organs was
      managed either through an enlarged port (phi 2 cm.) or by joining vertically the
      stabs of the two ports lateral to the sarcospinalis muscle. The average operative
      time was 4.10 hours) range 2.30-5.20). Both CO2 absorption and blood loss were
      negligible. No major complications were observed. Postoperative pain never
      required medications. All patients were able to stand on the 1st postoperative
      day. Mean postoperative hospitalisation was 4 days. Direct retroperitoneal
      approach provides optimal access for laparoscopic renal, proximal ureteral and
      adrenal surgery, avoiding extensive dissection and handling of intraperitoneal
      structures.

PMID- 7646004
TI  - Bladder laparoscopic surgery.
AB  - The advances made in laparoscopic surgery during the last five years have made
      possible the performance of a variety of bladder level procedures as suspension
      of the bladder neck, removal of bladder diverticulum and cystectomy. Laparoscopic
      bladder-neck suspension is purposed by different Authors as a minimally invasive
      procedure that can be provide efficacious results as like as open surgery,
      reducing post-operative disconfort. All different laparoscopic technique provide
      good results at short-term follow-up. A longer follow-up period is required for
      the evaluation of the effective efficacy of this treatment. In according with
      other authors, our experience with laparoscopic bladder diverticulectomy
      demonstrates the feasibility and the potentiality of this technique. Up to now
      this procedure has been employed in the treatment of diverticula involved in
      urinary infection or residual urine. At the beginning, laparoscopic cystectomy
      has been purposed in patients with begin disease; more recently, laparoscopy has
      been disease; more recently, laparoscopy has been employed for cystectomy in case
      of bladder cancer. The few cases described demonstrate that the technique is
      feasible but, until now, laparoscopic cystectomy has been reported just in female
      patients.

PMID- 7646005
TI  - Randomly amplified polymorphic DNA analysis of Xylella fastidiosa Pierce's
      disease and oak leaf scorch pathotypes.
AB  - Randomly amplified polymorphic DNA analysis was conducted with 14 primers to 17
      strains of Xylella fastidiosa. There was a high degree of similarity among the
      seven Pierce's disease (PD) strains (Sxy > 0.93) and the seven oak leaf scorch
      (OLS) strains (Sxy > 0.96). However, the two groups were different, with a
      similarity index of 0.67, confirming the presence of a PD DNA cluster and
      suggesting the presence of a new OLS cluster. The control plum leaf scald strains
      (two strains) together with the periwinkle wilt strain had a much smaller
      similarity index (0.44) compared with the PD and OLS clusters.

PMID- 7646006
TI  - Characterization of diverse 2,4-dichlorophenoxyacetic acid-degradative plasmids
      isolated from soil by complementation.
AB  - The diversity of 2,4-dichlorophenoxyacetic acid (2,4-D)-degradative plasmids in
      the microbial community of an agricultural soil was examined by complementation.
      This technique involved mixing a suitable Alcaligenes eutrophus (Rifr) recipient
      strain with the indigenous microbial populations extracted from soil. After
      incubation of this mixture, Rifr recipient strains which grow with 2,4-D as the
      only C source were selected. Two A. eutrophus strains were used as recipients:
      JMP228 (2,4-D-), which was previously derived from A. eutrophus JMP134 by curing
      of the 2,4-D-degradative plasmid pJP4, and JMP228 carrying pBH501aE (a plasmid
      derived from pJP4 by deletion of a large part of the tfdA gene which encodes the
      first step in the mineralization of 2,4-D). By using agricultural soil that had
      been treated with 2,4-D for several years, transconjugants were obtained with
      both recipients. However, when untreated control soil was used, no
      transconjugants were isolated. The various transconjugants had plasmids with
      seven different EcoRI restriction patterns. The corresponding plasmids are
      designated pEMT1 to pEMT7. Unlike pJP4, pEMT1 appeared not to be an IncP1
      plasmid, but all the others (pEMT2 to pEMT7) belong to the IncP1 group.
      Hybridization with individual probes for the tfdA to tfdF genes of pJP4
      demonstrated that all plasmids showed high degrees of homology to the tfdA gene.
      Only pEMT1 showed a high degree of homology to tfdB, tfdC, tfdD, tfdE, and tfdF,
      while the others showed only moderate degrees of homology to tfdB and low degrees
      of homology to tfdC.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7646007
TI  - Characterization of a new lipopeptide surfactant produced by thermotolerant and
      halotolerant subsurface Bacillus licheniformis BAS50.
AB  - Strain BAS50, isolated from a petroleum reservoir at a depth of 1,500 m and
      identified as Bacillus licheniformis, grew and produced a lipopeptide surfactant
      when cultured on a variety of substrates at salinities of up to 13% NaCl.
      Surfactant production occurred both aerobically and anaerobically and was optimal
      at 5% NaCl and temperatures between 35 and 45 degrees C. The biosurfactant,
      termed lichenysin A, was purified and chemically characterized. A tentative
      structure and composition for the surfactant are described. Lichenysin A is a
      mixture of lipopeptides, with the major components ranging in size from 1,006 to
      1,034 Da. The lipid moiety contains a mixture of 14 linear and branched beta
      hydroxy fatty acids ranging in size from C12 to C17. There are seven amino acids
      per molecule. The peptide moiety is composed of the following amino acids:
      glutamic acid as the N-terminal amino acid, asparagine, valine, leucine, and
      isoleucine as the C-terminal amino acid, at a ratio of 1.1:1.1:1.0:2.8:1.0,
      respectively. Purified lichenysin A decreases the surface tension of water from
      72 mN/m to 28 mN/m and achieves the critical micelle concentration with as little
      as 12 mg/liter, characterizing the product as a powerful surface-active agent
      that compares favorably to others surfactants. The antibacterial activity of
      lichenysin A has been demonstrated.

PMID- 7646008
TI  - Comparison of two methods for detection of Giardia cysts and Cryptosporidium
      oocysts in water.
AB  - The steps of two immunofluorescent-antibody-based detection methods were
      evaluated for their efficiencies in detecting Giardia cysts and Cryptosporidium
      oocysts. The two methods evaluated were the American Society for Testing and
      Materials proposed test method for Giardia cysts and Cryptosporidium oocysts in
      low-turbidity water and a procedure employing sampling by membrane filtration,
      Percoll-Percoll step gradient, and immunofluorescent staining. The membrane
      filter sampling method was characterized by higher recovery rates in all three
      types of waters tested: raw surface water, partially treated water from a
      flocculation basin, and filtered water. Cyst and oocyst recovery efficiencies
      decreased with increasing water turbidity regardless of the method used.
      Recoveries of seeded Giardia cysts exceeded those of Cryptosporidium oocysts in
      all types of water sampled. The sampling step in both methods resulted in the
      highest loss of seeded cysts and oocysts. Furthermore, much higher recovery
      efficiencies were obtained when the flotation step was avoided. The membrane
      filter method, using smaller tubes for flotation, was less time-consuming and
      cheaper. A serious disadvantage of this method was the lack of confirmation of
      presumptive cysts and oocysts, leaving the potential for false-positive Giardia
      and Cryptosporidium counts when cross-reacting algae are present in water
      samples.

PMID- 7646009
TI  - Properties of poly(3-hydroxybutyrate) depolymerase from a marine bacterium,
      Alcaligenes faecalis AE122.
AB  - Alcaligenes faecalis AE122 that used poly(3-hydroxybutyrate) (PHB) as a sole
      source of carbon was newly isolated from a coastal seawater sample. The strain
      required seawater for growth on PHB as well as in a nutrient broth, in which
      seawater could be replaced by an appropriate concentration of NaCl. PHB
      depolymerase was purified to homogeneity from the culture supernatant of A.
      faecalis AE122 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The
      enzyme consisted of a monomer subunit with a molecular mass of 95.5 kDa. The N
      terminal amino acid sequence was GAWQNNLAGGFNKV. The dimeric and trimeric esters
      of 3-hydroxybutyrate were the main hydrolysis products of the purified enzyme.
      The enzyme was most active at pH 9.0 and 55 degrees C and was inhibited by
      phenylmethylsulfonyl fluoride. Several cations in seawater greatly enhanced the
      enzyme activity.

PMID- 7646010
TI  - Susceptibility of suspended and surface-attached Salmonella enteritidis to
      biocides and elevated temperatures.
AB  - The differential resistance of substratum-attached, detached, and planktonic
      cells of Salmonella enteritidis phage type 4 was studied by using several
      inimical processes and in vivo bioluminescence as a nondestructive, real-time
      reporter of metabolic activity. Bioluminescence in this strain was mediated by a
      construction containing the entire lux operon from Photorhabdus luminescens. An
      excellent correlation between bioluminescence and classical plate count data was
      obtained when we compared attachment profiles, biocide concentration exponents,
      and thermal inactivation D values (D value was the time required for a 10-fold
      reduction in the number of survivors). Biocide challenge of surface-adherent S.
      enteritidis resulted in concentration exponents that were experimentally
      indistinguishable from those obtained with Luria-Bertani broth-grown planktonic
      cells. It appears that cleansing regimes developed by using planktonic cell data
      are effective against surface-attached cells of this bacterium. Both attached and
      detached cells exhibited an approximately twofold increase in D values at 52
      degrees C compared with values calculated for planktonic cells, strongly
      indicating that the detached cells exhibited an attached phenotype during the
      heating process. A model of a physiological adaptive response induced in attached
      cells and also reflected in detached cells is presented.

PMID- 7646011
TI  - Construction and use of a nontoxigenic strain of Pseudomonas aeruginosa for the
      production of recombinant exotoxin A.
AB  - To express recombinant forms of Pseudomonas aeruginosa exotoxin A in high yield,
      we have developed a nontoxigenic strain of P. aeruginosa derived from the
      hypertoxigenic strain PA103. The nontoxigenic strain, designated PA103A, was
      produced by the excision marker rescue technique to replace the toxA structural
      gene in PA103 with an insertionally inactivated toxA gene. The PA103A strain
      (ToxA-) was used subsequently as the host strain for the expression and
      production of several recombinant versions of exotoxin A, and the results were
      compared with exotoxin A production in other P. aeruginosa and Escherichia coli
      strains. Use of the PA103A strain transformed with the high-copy-number pRO1614
      plasmid bearing various toxA alleles resulted in final purification yields of
      exotoxin A averaging 23 mg/liter of culture. By comparison, exotoxin A production
      in other expression systems and host strains yields approximately 1/4 to 1/10 as
      much toxin.

PMID- 7646012
TI  - Influence of different chemical treatments on transport of Alcaligenes paradoxus
      in porous media.
AB  - Seven chemicals, three buffers, and a salt solution known to affect bacterial
      attachment were tested to quantify their abilities to enhance the penetration of
      Alcaligenes paradoxus in porous media. Chemical treatments included Tween 20 (a
      nonionic surfactant that affects hydrophobic interactions), sodium dodecyl
      sulfate (an anionic surfactant), EDTA (a cell membrane permeabilizer that removes
      outer membrane lipopolysaccharides), sodium PPi (a surface charge modifier),
      sodium periodate (an oxidizer that cleaves surface polysaccharides), lysozyme (an
      enzyme that cleaves cell wall components), and proteinase K (a nonspecific
      protease that cleaves peptide bonds). Buffers included MOPS [3-(N
      morpholino)propanesulfonic acid], Tris, phosphate, and an unbuffered solution
      containing only NaCl. Transport characteristics in the porous media were compared
      by using a sticking coefficient, alpha, defined as the rate at which particles
      stick to a grain of medium divided by the rate at which they strike the grain.
      Tween 20 reduced alpha by 2.5 orders of magnitude, to alpha = 0.0016, and was the
      most effective chemical treatment for decreasing bacterial attachment to glass
      beads in buffered solutions. Similar reductions in alpha were achieved in
      unbuffered solutions by reducing the solution ionic strength to 0.01 mM. EDTA,
      protease, and other treatments designed to alter cell structures did not reduce
      alpha by more than an order of magnitude. The number of bacteria retained by the
      porous media was decreased by treatments that made A. paradoxus more hydrophobic
      and less electrostatically charged, although alpha was poorly correlated with
      electrophoretic mobility and hydrophobicity index measurements at lower alpha
      values.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7646013
TI  - Cellodextrin efflux by the cellulolytic ruminal bacterium Fibrobacter
      succinogenes and its potential role in the growth of nonadherent bacteria.
AB  - When glucose or cellobiose was provided as an energy source for Fibrobacter
      succinogenes, there was a transient accumulation (as much as 0.4 mM hexose
      equivalent) of cellobiose or cellotriose, respectively, in the growth medium.
      Nongrowing cell suspensions converted cellobiose to cellotriose and longer-chain
      cellodextrins, and in this case the total cellodextrin concentration was as much
      as 20 mM (hexose equivalent). Because cell extracts of glucose- or cellobiose
      grown cells cleaved cellobioise and cellotriose by phosphate-dependent reactions
      and glucose 1-phosphate was an end product, it appeared that cellodextrins were
      being produced by a reversible phosphorylase reaction. This conclusion was
      supported by the observation that the ratio of cellodextrins to cellodextrins
      with one greater hexose [n/(n + 1)] was approximately 4, a value similar to the
      equilibrium constant (Keq) of cellobiose phosphorylase (J. K. Alexander, J.
      Bacteriol. 81:903-910, 1961). When F. succinogenes was grown in a cellobiose
      limited chemostat, cellobiose and cellotriose could both be detected, and the
      ratio of cellotriose to cellobiose was approximately 1 to 4. On the basis of
      these results, cellodextrin production is an equilibrium (mass action) function
      and not just an artifact of energy-rich cultural conditions. Cellodextrins could
      not be detected in low-dilution-rate, cellulose-limited continuous cultures, but
      these cultures had a large number of nonadherent cells. Because the nonadherent
      cells had a large reserve of polysaccharide and were observed at all stages of
      cell division, it appeared that they were utilizing cellodextrins as an energy
      source for growth.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7646014
TI  - Influence of various dust sampling and extraction methods on the measurement of
      airborne endotoxin.
AB  - The influence of various filter types and extraction conditions on the
      quantitation of airborne endotoxin with the Limulus amebocyte lysate test was
      studied by using airborne dusts sampled in a potato processing plant. Samples
      were collected with an apparatus designed to provide parallel samples. Data from
      the parallel-sampling experiment were statistically evaluated by using analysis
      of variance. In addition, the influence of storage conditions on the detectable
      endotoxin concentration was investigated by using commercially available
      lipopolysaccharides (LPS) and endotoxin-containing house dust extracts. The
      endotoxin extraction efficiency of 0.05% Tween 20 in pyrogen-free water was seven
      times higher than that of pyrogen-free water only. Two-times-greater amounts of
      endotoxin were extracted from glass fiber, Teflon, and polycarbonate filters than
      from cellulose ester filters. The temperature and shaking intensity during
      extraction were not related to the extraction efficiency. Repeated freeze (-20
      degrees C)-and-thaw cycles with commercial LPS reconstituted in pyrogen-free
      water had a dramatic effect on the detectable endotoxin level. A 25% loss in
      endotoxin activity per freeze-thaw cycle was observed. Storage of LPS samples for
      a period of 1 year at 7 degrees C had no effect on the endotoxin level. House
      dust extracts showed a decrease of about 20% in the endotoxin level after they
      had been frozen and thawed for a second time. The use of different container
      materials (borosilicate glass, "soft" glass, and polypropylene) did not result in
      different endotoxin levels. This study indicates that the assessment of endotoxin
      exposure may differ considerably between groups when different sampling,
      extraction, and storage procedures are employed.

PMID- 7646015
TI  - Purification and characterization of an extracellular alpha-amylase from
      Clostridium perfringens type A.
AB  - An alpha-amylase (EC 3.2.1.1) secreted by Clostridium perfringens NCTC 8679 type
      A was purified to homogeneity and characterized. It was isolated from
      concentrated cell-free culture medium by ion-exchange and gel permeation
      chromatography. The enzyme exhibited maximal activity at pH 6.5 and 30 degrees C
      without the presence of calcium. The pI of the enzyme was 4.75. The estimated
      molecular weight of the purified enzyme was 76 kDa. The purified enzyme was
      inactivated between 35 and 40 degrees C, which increased to between 45 and 50
      degrees C in the presence of calcium (5 mM). The purified enzyme produced a
      mixture of oligosaccharides as major end products of starch hydrolysis,
      indicating alpha-amylase activity.

PMID- 7646018
TI  - Purification and structural determination of an inhibitor of starfish oocyte
      maturation from a Bacillus species.
AB  - Inhibitors of bacterial origins of starfish oocyte maturation were sought to
      obtain biologically active substances which act on either hormonal signal
      transduction or cell cycle regulation. An oocyte maturation-inhibiting substance
      found in culture fluid of a Bacillus species was purified to homogeneity. This
      substance possessed the nature of a detergent and specifically inhibited 1
      methyladenine-induced oocyte maturation (50% inhibitory concentration, 3.3
      microM) but not dithiothreitol-induced maturation. Its total structure was
      established to be the lactone of 3-hydroxy-13-methyltetradecanoyl-Glu-Leu-Leu-Val
      Asp-Leu -Leu through COOH of the carboxy-terminal Leu. This structure is
      identical to surfactin, although although the configuration of the substance's
      amino acid residues has not yet been determined. Surfactin was shown to be
      identical with this substance in its inhibitory effect on starfish oocyte
      maturation as well as its chromatographic and electrophoretic properties.
      Therefore, it was concluded that the oocyte maturation-inhibiting substance
      produced by a Bacillus species is surfactin.

PMID- 7646017
TI  - Genetic structure of a lotic population of Burkolderia (Pseudomonas) cepacia.
AB  - The genetic structure of a population of Burkholderia (Pseudomonas) cepacia
      isolated from a southeastern blackwater stream was investigated by using
      multilocus enzyme electrophoresis to examine the allelic variation in eight
      structural gene loci. Overall, 213 isolates were collected at transect points
      along the stream continuum, from both the sediments along the bank and the water
      column. Multilocus enzyme electrophoresis analysis revealed 164 distinct
      electrophoretic types, and the mean genetic diversity of the entire population
      was 0.574. Genetic diversity values did not vary spatially along the stream
      continuum. From a canonical discriminant analysis, Mahalonobis distances
      (measurements of genetic similarity between populations) revealed significant
      differences among the subpopulations at the sediment sampling points, suggesting
      bacterial adaptation to a heterogeneous (or patchy) microgeographical
      environment. Multilocus linkage disequilibrium analysis of the isolates revealed
      only limited association between alleles, suggesting frequent recombination,
      relative to binary fission, in this population. Furthermore, the dendrogram
      created from the data of this study and the allele mismatch distribution are
      typical of a population characterized by extensive genetic mixing. We suggest
      that B. cepacia be added to the growing list of bacteria that are not
      obligatorily clonal.

PMID- 7646016
TI  - Effect of heat treatment on survival of, and growth from, spores of
      nonproteolytic Clostridium botulinum at refrigeration temperatures.
AB  - Spores of five type B, five type E, and two type F strains of nonproteolytic
      Clostridium botulinum were inoculated into tubes of an anaerobic meat medium plus
      lysozyme to give approximately 10(6) spores per tube. Sets of tubes were then
      subjected to a heat treatment, cooled, and incubated at 6, 8, 10, 12, and 25
      degrees C for up to 60 days. Treatments equivalent to heating at 65 degrees C for
      364 min, 70 degrees C for 8 min, and 75 degrees C for 27 min had little effect on
      growth and toxin formation. After a treatment equivalent to heating at 85 degrees
      C for 23 min, growth occurred at 6 and 8 degrees C within 28 to 40 days. After a
      treatment equivalent to heating at 80 degrees C for 19 min, growth occurred in
      some tubes at 6, 8, 10, or 12 degrees C within 28 to 53 days and at 25 degrees C
      in all tubes within 15 days. Following a treatment equivalent to heating at 95
      degrees C for 15 mine, growth was detected in some tubes incubated at 25 degrees
      C for fewer than 60 days but not in tubes incubated at 6 to 12 degrees C. The
      results indicate that heat treatment of processed foods equivalent to maintenance
      at 85 degrees C for 19 min combined with storage below 12 degrees C and a shelf
      life of not more than 28 days would reduce the risk of growth from spores of
      nonproteolytic C. botulinum by a factor of 10(6).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7646019
TI  - Precision and accuracy of recovery of Legionella pneumophila from seeded tap
      water by filtration and centrifugation.
AB  - Determination of the concentration of Legionella pneumophila in environmental
      water sites may be useful for the prediction of the risk of a particular site's
      causing Legionnaires' disease as well as for experimental studies of
      environmental growth or remediation. The precision and accuracy of recovery of
      two different L. pneumophila strains from seeded tap water samples were studied,
      with either filtration or centrifugation used to concentrate the bacteria. L.
      pneumophila grown on BCYE alpha agar or in Acanthamoeba castellanii was used to
      seed sterile tap water. Water samples were then either filtered (0.2-microns pore
      size) or centrifuged. An average of 53% (95% confidence interval [CI], 47 to 58%;
      n = 45) of the seeded L. pneumophila organisms were recovered by filtration with
      flat polycarbonate membranes. This recovery was significantly higher (P < 0.01)
      than that obtained by filtration with cast membranes (mean, 13%; 95% CI, 11 to
      38%; n = 4) or by centrifugation at 3,800 x g for 30 min (mean, 14%; 95% CI, 2 to
      25%; n = 9) or at 8,150 x g for 15 min (mean, 32%; 95% CI, 28 to 36%; n = 19).
      Recovery of L. pneumophila was not significantly different whether the bacteria
      were grown on plates or in amoebae. Use of a selective medium did not decrease
      the recovery efficiency, but preplating acid treatment of specimens caused an
      approximately 30% bacterial loss.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7646020
TI  - Identification of Rhizobium spp. in peat-based inoculants by DNA hybridization
      and PCR and its application in inoculant quality control.
AB  - Procedures based on DNA hybridization and PCR were developed for quality control
      of Rhizobium inoculants. Inoculants for pea and goat's rue were produced by
      Elomestari Ltd., Juva, Finland, in sterile dry fine peat by the standard
      procedure used by the company. The inoculants contained Rhizobium galegae HAMBI
      1174 and HAMBI 1207 and an R. leguminosarum biovar vicia strain, 16HSA, either
      solely or in combinations of two or three strains. DNA was isolated from 1-g
      samples of each peat inoculant and analyzed by nonradioactive DNA-DNA
      hybridization and by PCR. The hybridization probes were total DNAs from pure
      cultures of R. galegae HAMBI 1207 and R. leguminosarum biovar viciae 16HSA and a
      264-bp strain-specific fragment from the genome of R. galegae HAMBI 1174. The
      total DNA probes distinguished inoculants containing R. galegae or R.
      leguminosarum, and the strain-specific probe distinguished inoculants containing
      R. galegae HAMBI 1174. The hybridization results for R. galegae were verified in
      a PCR experiment by amplifying an R. galegae species-specific fragment and an R.
      galegae HAMBI 1174 strain-specific fragment in the same reaction. When suitable
      probes and primers are available, the methods described here offer promising
      alternatives for the quality control of peat-based inoculants.

PMID- 7646021
TI  - Activity and purification of linenscin OC2, an antibacterial substance produced
      by Brevibacterium linens OC2, an orange cheese coryneform bacterium.
AB  - An orange cheese coryneform bacterium isolated from the surface of Gruyere of
      Comte and identified as Brevibacterium linens produces an antimicrobial substance
      designated linenscin OC2. This compound inhibits gram-positive food-borne
      pathogens including Staphylococcus aureus and Listeria monocytogenes but is not
      active against gram-negative bacteria. Linenscin OC2 caused viability loss and
      lysis of the test organism, Listeria innocua. Electron microscopy showed that
      linenscin OC2 induces protoplast formation and cell lysis. The native substance
      is resistant to proteolytic enzymes, heat, and organic solvents and stable over a
      wide range of pH. The molecular weight of the native linenscin OC2 was estimated
      by gel chromatography to be over 285,000. Linenscin OC2 was purified by ammonium
      sulfate precipitation, 2-propanol extraction, and reverse-phase chromatography.
      Direct detection of antimicrobial activity on a sodium dodecyl sulfate
      polyacrylamide gel suggested an apparent molecular mass under 2,412 Da. Molecular
      mass was determined to be 1,196.7 Da by mass spectrometry. Amino acid composition
      analysis indicated that linenscin OC2 may contain 12 residues.

PMID- 7646022
TI  - Influence of the RpoS (KatF) sigma factor on maintenance of viability and
      culturability of Escherichia coli and Salmonella typhimurium in seawater.
AB  - The sigma factor RpoS is essential for stationary-phase-specific, multiple-stress
      resistance. We compared the viabilities (direct viable counts) and
      culturabilities (colony counts) in seawater of Escherichia coli and Salmonella
      typhimurium strains and those in which rpoS was deleted or which were deficient
      in guanosine 3',5'-bispyrophosphate (ppGpp) synthesis (relA spoT). RpoS, possibly
      via ppGpp regulation, positively influenced the culturability of these bacteria
      in oligotrophic seawater. This influence closely depended, however, upon the
      growth state of the cells and the conditions under which they were grown prior to
      their transfer to seawater. The protective effect of RpoS was observed only in
      stationary-phase cells grown at low osmolarity. A previous exposure of cells to
      high osmolarity (0.5 M NaCl) also had a strong influence on the effect of RpoS on
      cell culturability in seawater. Both E. coli and S. typhimurium RpoS mutants lost
      the ability to acquire a high resistance to seawater, as observed in both
      logarithmic-phase and stationary-phase RpoS+ cells grown at high osmolarity. A
      previous growth of S. typhimurium cells under anoxic conditions also modulated
      the incidence of RpoS on their culturability. When grown anaerobically at high
      osmolarity, logarithmic-phase S. typhimurium RpoS+ cells partly lost their
      resistance to seawater through preadaptation to high osmolarity. When grown
      anaerobically at high osmolarity until stationary phase, both RpoS+ and RpoS-
      cells retained very high levels of both viability and culturability and then did
      not enter the viable but nonculturable state for over 8 days in seawater because
      of an RpoS-independent, unknown mechanism.

PMID- 7646023
TI  - Flow cytometric analysis of activated sludge with rRNA-targeted probes.
AB  - Samples from a wastewater treatment plant were hybridized with fluorescein
      labeled oligonucleotide probes specific for members of the domains Bacteria and
      Eucarya; the alpha, beta, and gamma subclasses of the class Proteobacteria; or
      the genus Acinetobacter. Subsequently, they were counterstained with the DNA
      specific dye Hoechst 33342 and analyzed by flow cytometry. By quantifying forward
      angle light scatter and Hoechst- and probe-conferred fluorescence as measures for
      cell size, DNA content, and rRNA content, respectively, not only relative
      abundances but also assessments of general metabolic activity for each of these
      groups were obtained. Hybridizations with a positive control probe binding to all
      bacteria showed that in the activated-sludge samples examined, 70 to 80% of the
      Hoechst-stained cells could unambiguously be identified by this method. The
      majority of the detected cells (approximately 40%) were beta-subclass
      Proteobacteria. Flow cytometric and microscopic counts were in general agreement.
      Discrepancies were found in particular for those populations that occurred
      predominantly in flocs (alpha subclass of the Proteobacteria) or chains
      (Acinetobacter spp.). Although the dispersal of aggregates needs to be improved,
      flow cytometry combined with rRNA-based in situ probing appears to be a powerful
      tool for the rapid and highly automated analysis of the microbial communities in
      activated sludge.

PMID- 7646025
TI  - Lignin oxidation by laccase isozymes from Trametes versicolor and role of the
      mediator 2,2'-azinobis(3-ethylbenzthiazoline-6-sulfonate) in kraft lignin
      depolymerization.
AB  - Two laccase isozymes (I and II) produced by the white-rot fungus Trametes
      versicolor were purified, and their reactivities towards various substrates and
      lignins were studied. The N-terminal amino acid sequences of these enzymes were
      determined and compared to other known laccase sequences. Laccase II showed a
      very high sequence similarity to a laccase which was previously reported to
      depolymerize lignin. The reactivities of the two isozymes on most of the
      substrates tested were similar, but there were some differences in the oxidation
      rate of polymeric substrates. We found that the two laccases produced similar
      qualitative effects on kraft lignin and residual lignin in kraft pulp, with no
      evidence of a marked preference for depolymerization by either enzyme. However,
      the presence of the mediator 2,2'-azinobis(3-ethylbenzthiazoline-6-sulfonate)
      prevented and reversed the polymerization of kraft lignin by either laccase. The
      delignification of hardwood and softwood kraft pulps with the two isozymes and
      the mediator was compared; either laccase was able to reduce the kappa number of
      pulp, but only in the presence of 2,2'-azinobis(3-ethylbenzthiazoline-6
      sulfonate).

PMID- 7646024
TI  - xylA cloning and sequencing and biochemical characterization of xylose isomerase
      from Thermotoga neapolitana.
AB  - The xylA gene coding for xylose isomerase from the hyperthermophile Thermotoga
      neapolitana 5068 was cloned, sequenced, and expressed in Escherichia coli. The
      gene encoded a polypeptide of 444 residues with a calculated molecular weight of
      50,892. The native enzyme was a homotetramer with a molecular weight of 200,000.
      This xylose isomerase was a member of the family II enzymes (these differ from
      family I isomerases by the presence of approximately 50 additional residues at
      the amino terminus). The enzyme was extremely thermostable, with optimal activity
      above 95 degrees C. The xylose isomerase showed maximum activity at pH 7.1, but
      it had high relative activity over a broad pH range. The catalytic efficiency
      (kcat/Km) of the enzyme was essentially constant between 60 and 90 degrees C, and
      the catalytic efficiency decreased between 90 and 98 degrees C primarily because
      of a large increase in Km. The T. neapolitana xylose isomerase had a higher
      turnover number and a lower Km for glucose than other family II xylose
      isomerases. Comparisons with other xylose isomerases showed that the catalytic
      and cation binding regions were well conserved. Comparison of different xylose
      isomerase sequences showed that numbers of asparagine and glutamine residues
      decreased with increasing enzyme thermostability, presumably as a thermophilic
      strategy for diminishing the potential for chemical denaturation through
      deamidation at elevated temperatures.

PMID- 7646026
TI  - Survival of fecal microorganisms in marine and freshwater sediments.
AB  - The survival of culturable fecal coliforms, fecal streptococci, and Clostridium
      perfringens spores in freshwater and marine sediments from sites near sewage
      outfalls was studied. In laboratory studies, the inhibition of protozoan
      predators with cycloheximide allowed the fecal coliforms to grow in the sediment
      whereas the presence of predators resulted in a net die-off. C. perfringens
      spores did not appear either to be affected by predators or to die off throughout
      the duration of the experiments (28 days). Studies using in situ membrane
      diffusion chambers showed that, with the exception of C. perfringens, die-off of
      the test organisms to 10% of their initial numbers occurred in both marine and
      freshwater sediments within 85 days. The usual exponential decay model could not
      be applied to the sediment survival data, with the exception of the data for
      fecal streptococci. It was concluded that application of the usual decay model to
      the fecal coliform data was confounded by the complex relationship between growth
      and predation. The survival of seeded Escherichia coli in marine sediment was
      studied by using an enumeration method which detected viable but nonculturable
      bacteria. Throughout the duration of the experiment (68 days), the same
      proportion of E. coli organisms remained culturable, suggesting that sediment
      provides a favorable, nonstarvation environment for the bacteria.

PMID- 7646027
TI  - Activation of plasma membrane H(+)-ATPase and expression of PMA1 and PMA2 genes
      in Saccharomyces cerevisiae cells grown at supraoptimal temperatures.
AB  - During exponential growth at temperatures of 30 to 39 degrees C, the specific
      activity of H(+)-ATPase in the plasma membrane of Saccharomyces cerevisiae
      (assayed at the standard temperature 30 degrees C) increased with increases in
      growth temperature. In addition, the optimal temperature for in vitro activity of
      this ATPase was 42 degrees C. Therefore, the maximum values of ATPase activity
      were expected to occur in cells that grew within the supraoptimal range of
      temperatures. Activation induced by supraoptimal temperatures was not the result
      of increased synthesis of this membrane enzyme. When the growth temperature
      increased from 30 to 40 degrees C, expression of the essential PMA1 gene,
      monitored either by the level of PMA1 mRNA or the beta-galactosidase activity of
      the lacZ-PMA1 fusion, was reduced. Consistently, quantitative immunoassays showed
      that the ATPase content in the plasma membrane decreased. Like ATPase activity,
      the efficiency of the PMA2 promoter increased with increases in growth
      temperature in cells that had been grown at 30 to 39 degrees C, but its level of
      expression was several hundred-fold lower than that of PMA1. These results
      suggest that the major PMA1 ATPase is activated at supraoptimal temperatures.

PMID- 7646028
TI  - Tri6 encodes an unusual zinc finger protein involved in regulation of
      trichothecene biosynthesis in Fusarium sporotrichioides.
AB  - In Fusarium sporotrichioides, several genes required for biosynthesis of the
      trichothecene mycotoxin T-2 toxin are closely linked. Further characterization of
      this gene cluster has revealed a gene, Tri6, that specifies a 217-amino-acid
      protein with regions similar to Cys2His2 zinc finger proteins. Temporal
      expression of Tri6 is similar to that of trichothecene biosynthetic pathway
      genes. Analysis of Tri6 transcripts indicated that transcription is initiated in
      two regions and that within each region there may be at least four initiation
      sites. Disruption of Tri6 resulted in a mutant that did not produce
      trichothecenes but that did accumulate low levels of the trichothecene precursor
      trichodiene. The Tri6 mutant was unable to convert six trichothecene biosynthetic
      intermediates to T-2 toxin, and transcription of two biosynthetic genes, Tri4 and
      Tri5, was greatly reduced in the mutant relative to the wild type. In addition,
      the product of Tri6 functioned as a transcriptional activator in Saccharomyces
      cerevisiae when fused to the DNA binding region of GAL4. These results indicate
      that Tri6 encodes a protein involved in the transcriptional regulation of
      trichothecene biosynthetic genes in F. sporotrichioides.

PMID- 7646029
TI  - Construction of a rhizosphere pseudomonad with potential to degrade
      polychlorinated biphenyls and detection of bph gene expression in the
      rhizosphere.
AB  - The genetically engineered transposon TnPCB, contains genes (bph) encoding the
      biphenyl degradative pathway. TnPCB was stably inserted into the chromosome of
      two different rhizosphere pseudomonads. One genetically modified strain,
      Pseudomonas fluorescens F113pcb, was characterized in detail and found to be
      unaltered in important parameters such as growth rate and production of secondary
      metabolites. The expression of the heterologous bph genes in F113pcb was
      confirmed by the ability of the genetically modified microorganism to utilize
      biphenyl as a sole carbon source. The introduced trait remained stable in
      laboratory experiments, and no bph-negative isolates were found after extensive
      subculture in nonselective media. The bph trait was also stable in nonselective
      rhizosphere microcosms. Rhizosphere competence of the modified F113pcb was
      assessed in colonization experiments in nonsterile soil microcosms on sugar beet
      seedling roots. F113pcb was able to colonize as efficiently as a marked wild-type
      strain, and no decrease in competitiveness was observed. In situ expression of
      the bph genes in F113pcb was found when F113pcb bearing a bph'lacZ reporter
      fusion was inoculated onto sugar beet seeds. This indicates that the bph gene
      products may also be present under in situ conditions. These experiments
      demonstrated that rhizosphere-adapted microbes can be genetically manipulated to
      metabolize novel compounds without affecting their ecological competence.
      Expression of the introduced genes can be detected in the rhizosphere, indicating
      considerable potential for the manipulation of the rhizosphere as a self
      sustaining biofilm for the bioremediation of pollutants in soil. Rhizosphere
      bacteria such as fluorescent Pseudomonas spp. are ecologically adapted to
      colonize and compete in the rhizosphere environment. Expanding the metabolic
      functions of such pseudomonads to degrade pollutants may prove to be a useful
      strategy for bioremediation.

PMID- 7646030
TI  - Purification and characterization of the Bacillus subtilis levanase produced in
      Escherichia coli.
AB  - The enzyme levanase encoded by the sacC gene from Bacillus subtilis was
      overexpressed in Escherichia coli with the strong, inducible tac promoter. The
      enzyme was purified from crude E. coli cell lysates by salting out with ammonium
      sulfate and chromatography on DEAE-Sepharose CL-6B, S-Sepharose, and MonoQ
      Sepharose. The purified protein had an apparent molecular mass of 75,000 Da in
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis, which is in agreement
      with that expected from the nucleotide sequence. Levanase was active on levan,
      inulin, and sucrose with Km values of 1.2 microM, 6.8 mM, and 65 mM,
      respectively. The pH optimum of the enzyme acting on inulin was 5.5, and the
      temperature optimum was 55 degrees C. Levanase was rapidly inactivated at 60
      degrees C, but activity could be retained for longer times by adding fructose or
      glycerol. The enzyme activity was completely inactivated by Ag+ and Hg2+ ions,
      indicating that a sulfhydryl group is involved. A ratio of sucrase to inulinase
      activity of 1.2 was found for the purified enzyme with substrate concentrations
      of 50 mg/ml. The mechanism of enzyme action was investigated. No liberation of
      fructo-oligomers from inulin and levan could be observed by thin-layer
      chromatography and size exclusion chromatography-low-angle laser light scattering
      interferometric differential refractive index techniques. This indicates that
      levanase is an exoenzyme acting by the single-chain mode.

PMID- 7646031
TI  - Inactivation of rsmA leads to overproduction of extracellular pectinases,
      cellulases, and proteases in Erwinia carotovora subsp. carotovora in the absence
      of the starvation/cell density-sensing signal, N-(3-oxohexanoyl)-L-homoserine
      lactone.
AB  - The soft-rotting bacterium, Erwinia carotovora subsp. carotovora 71, produces
      extracellular enzymes such as pectate lyase isozymes (Pels), cellulase (Cel),
      polygalacturonase (Peh), and protease (Prt). While the extracellular levels of
      these enzymes are extremely low when the bacterium is grown in salts-yeast
      extract-glycerol (SYG) medium, the enzymatic activities are highly induced in SYG
      medium supplemented with celery extract. By transposon (mini-Tn5) mutagenesis, we
      isolated a RsmA- mutant, AC5070, which overproduces extracellular enzymes; the
      basal levels of Pel, Peh, and Cel in AC5070 are higher than the induced levels in
      the RsmA+ parent, AC5047. While Peh production is mostly constitutive in AC5070,
      Pel, Cel, and Prt production is still inducible with celery extract. The high
      basal levels of pel-1, pel-3, and peh-1 mRNAs in AC5070 demonstrate that
      overproduction of the pectolytic enzymes is due to the stimulation of
      transcription. Using chromosomal DNA flanking mini-Tn5 as a probe, we cloned the
      wild-type rsmA+ allele, which suppresses Pel, Peh, Cel, and Prt production in
      both RsmA+ and RsmA- strains. The RsmA- mutant, like its parent, produces N-(3
      oxohexanoyl)-L-homoserine lactone (HSL), a starvation/cell density-sensing signal
      required for extracellular enzyme production. To examine the role of HSL, we
      constructed HSL-deficient strains by replacing hslI, a locus required for HSL
      production, with hslI::Tn3HoHo1-Spc. While the basal levels of Pel, Peh, Cel, and
      Prt are comparable in the RsmA- mutant and its HSL- derivative, these enzymes are
      barely detectable in the Hsl- derivative of the RsmA+ parent strain.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7646032
TI  - Growth of Mycoplasma hyorhinis cultivar alpha on semisynthetic medium.
AB  - Serial passage of Mycoplasma hyorhinis cultivar alpha (formerly noncultivable
      strains) has been accomplished in modified CMRL-1066 medium with fetal bovine
      serum. In modified CMRL-1066 liquid medium, cultivar alpha strains grow at a
      similar rate and to equivalent titers when compared with BTS-7, the type strain
      of the species. Further experiments with BTS-7 demonstrate that the extent of
      growth obtained in the semidefined medium was comparable to growth in
      conventional mycoplasma medium. M. hyorhinis strains, including cultivar alpha
      strains, grow in serial passage when fetal bovine serum is replaced with bovine
      serum albumin, palmitic acid, and cholesterol. The results of these studies show
      that M. hyorhinis cultivar alpha strains are not nutritionally more fastidious
      than other mycoplasmas but that they are noncultivable on standard mycoplasma
      media because they are sensitive to high levels of inhibition activity by medium
      components.

PMID- 7646034
TI  - A mutant of Azospirillum brasilense Sp7 impaired in flocculation with a modified
      colonization pattern and superior nitrogen fixation in association with wheat.
AB  - We report here significant phenotypic and genetic differences between
      Azospirillum brasilense Sp7 and spontaneous mutant Sp7-S and their related
      properties in association with wheat. In contrast to the wild-type strain of Sp7,
      colonies of Sp7-S stained weakly with Congo red when grown on agar media
      containing the dye and did not flocculate in the presence of fructose and
      nitrate. Scanning and transmission electron micrographs showed clearly that the
      Sp7-S strain lacked surface materials present as a thick layer on the surface of
      the wild-type Sp7 strain. Different patterns of colonization on wheat roots
      between Sp7 and Sp7-S, revealed by in situ studies using nifA-lacZ as a reporter
      gene, were related to a large increase in nitrogenase activity (acetylene
      reduction) with Sp7-S in association with normal and 2,4-dichlorophenoxyacetic
      acid-treated wheat for assays conducted under conditions in which the nitrogenase
      activity of free-living Azospirillum organisms was inhibited by an excess of
      oxygen. Randomly amplified polymorphic DNA analysis indicated the close genetic
      relationship of Sp7-S to several other sources of Sp7, by comparison to other
      recognized strains of A. brasilense. Genetic complementation of Sp7-S was
      achieved with a 9.4-kb fragment of DNA cloned from wild-type Sp7, restoring Congo
      red staining and flocculation.

PMID- 7646033
TI  - Expression, purification, and characterization of the cellulose-binding domain of
      the scaffoldin subunit from the cellulosome of Clostridium thermocellum.
AB  - The major cellulose-binding domain (CBD) from the cellulosome of Clostridium
      thermocellum YS was cloned and overexpressed in Escherichia coli. The expressed
      protein was purified efficiently by a modification of a novel procedure termed
      affinity digestion. The properties of the purified polypeptide were compared with
      those of a related CBD derived from a cellulosome-like complex of a similar (but
      mesophilic) clostridial species, Clostridium cellulovorans. The binding
      properties of the two proteins with their common substrate were found to be very
      similar. Despite the similarity in the amino acid sequences of the two CBDs,
      polyclonal antibodies raised against the CBD from C. thermocellum failed to
      interact with the protein from C. cellulovorans. Chemical modification of the
      single cysteine of the CBD had little effect on the binding to cellulose.
      Biotinylation of this cysteine allowed the efficient binding of avidin to
      cellulose, and the resultant matrix is appropriate for use as a universal
      affinity system.

PMID- 7646035
TI  - Evaluation of new culture media for rapid detection and isolation of salmonellae
      in foods.
AB  - Conventional methods for Salmonella detection in foods can require up to 6 and at
      least 4 days. We have observed that the total analysis time can be reduced to 48
      h by using Salmosyst broth as a liquid medium for both preenrichment and
      selective enrichment and Rambach agar (RA), a new selective plate medium. In
      samples of artificially contaminated ground beef Salmonella enteritidis was
      detected at a concentration of 0.4 CFU/g (10 CFU/25 g) by both a conventional
      method and the new method. Of 519 samples of foods for sale, 38 were Salmonella
      positive by both methods while 471 were negative. Nine samples which were
      negative by the conventional method were positive by the Salmosyst-RA method,
      while one sample positive by the first method was negative by the last.
      Therefore, the Salmosyst-RA method showed 97.9% sensitivity compared with the
      81.2% sensitivity of the conventional method. The new method was also highly
      specific (98% specificity) in presumptive identification of Salmonella colonies.
      Furthermore, a 6-h preenrichment in Salmosyst broth has been proved sufficient
      for the repair of heat-injured Salmonella cells and for subsequent recovery by
      selective enrichment. In conclusion, the Salmosyst-RA method shows several
      advantages over both conventional and rapid noncultural methods: (i) only two
      media are required instead of the five media for conventional methods; (ii) in
      real time it is comparable to other rapid noncultural methods, which require 30
      to 31 h; (iii) it is highly sensitive and specific; and (iv) it allows the
      isolation of Salmonella strains which can be characterized by appropriate
      phenotypic and genotypic typing methods for epidemiological investigations.

PMID- 7646036
TI  - DNA polymorphisms in strains of Legionella pneumophila serogroups 3 and 4
      detected by macrorestriction analysis and their use for epidemiological
      investigation of nosocomial legionellosis.
AB  - Genomic DNAs of clinical and environmental isolates of Legionella pneumophila
      belonging to serogroups 3 and 4 were analyzed by macrorestriction analysis by
      pulsed-field gel electrophoresis. The restriction enzymes SfiI and NotI allowed
      easy visual separation of epidemiologically unrelated serogroup 3 strains. Three
      unrelated serogroup 3 strains that were isolated from different locations were
      identical by this genome mapping technique. Five unrelated serogroup 4 strains
      were separable by this technique. The electrophoretic patterns obtained after
      SfiI or NotI cleavage of the DNA of strains isolated from four patients with
      hospital-acquired legionellosis were identical to the patterns of strains
      isolated from the hot water supply systems of the buildings in which the patients
      were hospitalized. In conclusion, macrorestriction analysis is a valuable tool
      for epidemiological studies of infections caused by L. pneumophila serogroups 3
      and 4.

PMID- 7646037
TI  - A unique endoglucanase-encoding gene cloned from the phytopathogenic fungus
      Macrophomina phaseolina.
AB  - The deduced amino acid sequence derived from a Macrophomina phaseolina beta-1,4
      endoglucanase-encoding gene revealed 48% identity (over 119 amino acids) with
      egl1 from the phytopathogen Pseudomonas solanacearum. Its similarity to
      saprophyte endoglucanases was not significant. Its minimum substrate size, unlike
      that of any known saprophyte endoglucanase, was cellopentaose. The unique
      characteristics of M. phaseolina egl1-encoded endoglucanase suggest that it is
      phytopathogen specific.

PMID- 7646038
TI  - An indirect enzyme immunoassay for the mycotoxin citrinin.
AB  - An indirect competitive enzyme immunoassay using rabbit antisera could detect
      citrinin in buffer solutions at 1 to 13 ng/ml (0.05 to 0.65 ng per assay). Cross
      reactivity with austdiol, alternariol, ochratoxin A, and deoxynivalenol was <
      0.1% relative to citrinin. Recovery of citrinin added to wheat flour at 200 to
      2,000 ng/g was 89 to 104%, with a coefficient of variation of 6.9 to 13%.

PMID- 7646040
TI  - Adhesion of Listeria monocytogenes to silica surfaces after sequential and
      competitive adsorption of bovine serum albumin and beta-lactoglobulin.
AB  - Adsorbed bovine serum albumin was resistant to exchange with beta-lactoglobulin,
      and when albumin was adsorbed from a mixture, its surface concentration increased
      with time. The passivating character of adsorbed albumin and its resistance to
      desorption were consistent with the level of Listeria monocytogenes adhesion
      evoked by albumin-containing protein films.

PMID- 7646039
TI  - Surface phenotypic characteristics and virulence of Spanish isolates of Aeromonas
      salmonicida after passage through fish.
AB  - Eleven strains of Aeromonas salmonicida were passaged twice by intraperitoneal
      injection through rainbow trout and reisolated from the kidney of moribund fish.
      The surface characteristics and virulence of the strains changed following
      passage through fish. None of the in vitro tests used could effectively predict
      the in vivo virulence.

PMID- 7646041
TI  - Emergence of nylon oligomer degradation enzymes in Pseudomonas aeruginosa PAO
      through experimental evolution.
AB  - Through selective cultivation with 6-aminohexanoate linear dimer, a by-product of
      nylon-6 manufacture, as the sole source of carbon and nitrogen, Pseudomonas
      aeruginosa PAO, which initially has no enzyme activity to degrade this xenobiotic
      compound, was successfully expanded in its metabolic ability. Two new enzyme
      activities, 6-aminohexanoate cyclic dimer hydrolase and 6-aminohexanoate dimer
      hydrolase, were detected in the adapted strains.

PMID- 7646042
TI  - Cloning and characterization of the abortive infection genetic determinant abiD
      isolated from pBF61 of Lactococcus lactis subsp. lactis KR5.
AB  - A 6.3-kb fragment from pBF61 in Lactococcus lactis subsp. lactis KR5 was cloned
      and found to confer an abortive phage infection (Abi+) phenotype exhibiting a
      reduction in efficiency of plating and plaque size for small isometric- and
      prolate-headed bacteriophages sk1 and c2, respectively, and to produce a 10-fold
      decrease in c2 phage burst size. Phage adsorption was not significantly reduced.
      An open reading frame of 1,098 bp was sequenced and designated abiD. Tn5
      mutagenesis confirmed that abiD was required for the Abi+ phenotype.

PMID- 7646043
TI  - Spectrofluorometric assay for rapid detection of total and fecal coliforms from
      surface water.
AB  - With a spectrofluorometer, the length of the incubation time required in the
      fluorogenic assay was reduced to 12 h. The threshold emissions for reading the
      fluorogenic reaction by the spectrofluorometer were 5 and 10 U for lauryl
      tryptose broth media containing 4-methylumbelliferyl-beta-D-galactoside and 4
      methylumbelliferyl-beta-D-glucuronide, respectively. These two kinds of threshold
      units were equivalent to known concentrations of free 4-methylumbelliferone of
      2.5 and 6 microM, respectively, in lauryl tryptose broth media.

PMID- 7646044
TI  - Enumeration of transconjugated Ruminococcus albus and its survival in the goat
      rumen microcosm.
AB  - A transconjugant Ruminococcus albus A3 culture was released into a goat rumen,
      and the extent of its survival in the rumen microcosm was measured by
      distinguishing this bacterium from indigenous microbes by antibiotic resistance.
      A3 cells remained roughly constant for 14 days in this goat rumen.

PMID- 7646045
TI  - Starvation- and stationary-phase-induced acid tolerance in Escherichia coli
      O157:H7.
AB  - Stationary phase and the starvation of log-phase cells increased the acid
      tolerance of Escherichia coli O157:H7 strains. Although the degree of acid
      tolerance varied, the survival of most O157:H7 strains exceeded that of other,
      related, pathogens in a synthetic gastric fluid.

PMID- 7646046
TI  - Role of C-terminal direct repeating units of the Streptococcus mutans
      glucosyltransferase-S in glucan binding.
AB  - The C-terminal glucan-binding domain of the glucosyltransferase-S of
      Streptococcus mutans GS-5 contains five 65-amino-acid direct repeating units. A
      series of deletion derivatives of both the glucosyltransferase-S and its glucan
      binding domain were constructed and analyzed. The results demonstrated that the
      four C-terminal direct repeating units constituted part of the minimum domain
      required for glucan binding.

PMID- 7646047
TI  - Xylitol formation and reduction equivalent generation during anaerobic xylose
      conversion with glucose as cosubstrate in recombinant Saccharomyces cerevisiae
      expressing the xyl1 gene.
AB  - Glucose was used as a cosubstrate under anaerobic conditions in the conversion of
      xylose to xylitol by a recombinant Saccharomyces cerevisiae strain expressing the
      xyl1 gene. Glucose was metabolized mainly through glycolysis, with carbon
      dioxide, acetate, and ethanol as end products and with reduction equivalents
      generated in the glyceraldehyde-3-phosphate dehydrogenase and acetaldehyde
      dehydrogenase reactions. At a high glucose supply rate, generation of surplus
      reduction equivalents resulted in simultaneous ethanol formation. On the other
      hand, at a low glucose supply rate, additional reduction equivalents were
      generated by simultaneous ethanol consumption. A significantly lower xylitol
      formation rate was observed.

PMID- 7646048
TI  - Purification and characterization of xenorhabdicin, a phage tail-like
      bacteriocin, from the lysogenic strain F1 of Xenorhabdus nematophilus.
AB  - Xenorhabdicin, the phage tail-like bacteriocins of Xenorhabdus nematophilus, and
      phage head particles, elements produced together after mitomycin induction in X.
      nematophilus lysogenic strain F1 cultures, were separated by DEAE chromatography,
      examined by transmission electron microscopy, and characterized by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis. Electrophoresis of xenorhabdicin
      showed two major subunits of 43 and 20 kDa corresponding to the sheath and the
      inner core, respectively. At least five other minor subunits of 67, 54, 35, 28,
      and 16 kDa were also characterized. Electrophoresis of the phage head capsids
      showed a major 40-kDa subunit and two minor 50- and 34-kDa subunits. Bactericidal
      activity recorded against closely related bacterial species and spontaneously
      produced by X. nematophilus resides in the xenorhabdicin particles and is another
      antimicrobial barrier to save the symbiotic association.

PMID- 7646050
TI  - Cloning of the genes for degradation of the herbicides EPTC (S-ethyl
      dipropylthiocarbamate) and atrazine from Rhodococcus sp. strain TE1.
AB  - The degradation of the herbicides EPTC (S-ethyl dipropylthiocarbamate) and
      atrazine (2-chloro-4-ethyl-amino-6-isopropylamino-1,3,5-triazine) is associated
      with an indigenous plasmid in Rhodococcus sp. strain TE1. Plasmid DNA libraries
      of Rhodococcus sp. strain TE1 were constructed in a Rhodococcus-Escherichia coli
      shuttle vector, pBS305, and transferred into Rhodococcus sp. strain TE3, a
      derivative of Rhodococcus sp. strain TE1 lacking herbicide degradation activity,
      to select transformants capable of growing on EPTC as the sole source of carbon
      (EPTC+). Analysis of plasmids from the EPTC+ transformants indicated that the
      eptA gene, which codes for the enzyme required for EPTC degradation, residues on
      a 6.2-kb KpnI fragment. The cloned fragment also harbored the gene required for
      atrazine N dealkylation (atrA). The plasmid carrying the cloned fragment could be
      electroporated into a number of other Rhodococcus strains in which both eptA and
      atrA were fully expressed. No expression of the cloned genes was evident in E.
      coli strains. Subcloning of the 6.2-kb fragment to distinguish between EPTC- and
      atrazine-degrading genes was not successful.

PMID- 7646049
TI  - A single cytochrome P-450 system is involved in degradation of the herbicides
      EPTC (S-ethyl dipropylthiocarbamate) and atrazine by Rhodococcus sp. strain
      NI86/21.
AB  - During atrazine degradation by Rhodococcus sp. strain N186/21, N-dealkylated
      metabolites and an hydroxyisopropyl derivative are produced. The cytochrome P-450
      system that is involved in degradation of thiocarbamate herbicides by strain
      N186/21 (I. Nagy, G. Schoofs, F. Compernolle, P. Proost, J. Vanderleyden, and R.
      De Mot, J. Bacteriol. 177:676-687, 1995) is also required for atrazine
      degradation. Atrazine-degrading activity was conferred on the atrazine-negative
      strains, mutant FAJ2027 of Rhodococcus sp. strain N186/21 and Rhodococcus
      erythropolis SQ1, upon transformation with the genes encoding the cytochrome P
      450 system.

PMID- 7646051
TI  - Comparison of PCR and cell culture for detection of enteroviruses in sludge
      amended field soils and determination of their transport.
AB  - PCR and cell culture assays for enteroviruses were conducted on soil samples
      collected from an experimental farm that had received mesophilic anaerobically
      digested sludge for the past 7 years. Of 24 samples assayed, 21 samples were
      positive by PCR, implying that at least some viral nucleic acid sequences
      remained intact. However, these viral particles were unable to infect the Buffalo
      Green Monkey cell line used in subsequent cell culture assays. It is significant
      that positive PCR detection of nucleic acid sequences occurred even though the
      most recent sludge application was 3 months prior to soil sampling. Viral nucleic
      acid sequences were detected by PCR at points vertically and laterally displaced
      from sludge injections, illustrating significant transport of viruses. Rainfall
      and irrigation events may have contributed to viral transport.

PMID- 7646052
TI  - Truncated human P450 2D6: expression in Escherichia coli, Ni(2+)-chelate affinity
      purification, and characterization of solubility and aggregation.
AB  - Cytochrome P450 2D6 is one of the clinically important drug-oxidizing enzymes in
      human liver. We constructed an Escherichia coli expression vector to obtain large
      amounts of this microsomal hemoprotein in a form suitable for purification and
      further structural analysis. The N-terminal 25 amino acids, which presumably
      serve as a membrane anchor, were replaced by codons for a [His]6 tag to increase
      solubility and to allow for rapid purification by Ni(2+)-chelate affinity
      chromatography. P450 2D6 apoprotein was synthesized under practically all growth
      conditions, whereas formation of heme-containing holoenzyme strictly depended on
      addition of the heme precursor delta-aminolevulinic acid to the E. coli culture.
      The truncated P450 was purified from the soluble cytosolic fraction to
      electrophoretic homogeneity (7 nmol of P450/mg protein) by affinity
      chromatography on Ni(2+)-nitrilotriacetate-agarose. The purified protein
      exhibited a CO-reduced difference spectrum with a delta max at 450 nm and no
      detectable P420. Kinetic analysis revealed a Km value for bufuralol 1'
      hydroxylation similar to the Km of the native full-length enzyme purified from
      human liver microsomes. To characterize the purified truncated protein with
      respect to hydrodynamic properties, we performed sedimentation velocity and
      sedimentation equilibrium analysis. These studies demonstrated that approximately
      50% of the protein was in a highly aggregated state. Another 30% consisted of a
      single protein species with an approximated molecular weight of 200,000 and the
      residual 20% represented at least two other species with lower molecular weights.
      To prevent formation of such unexpectedly high aggregation states, purification
      was also performed in the presence of "nonaethyleneglycol monododecyl ether"
      (C12E9), a nonionic, chemically defined detergent often used in attempts to
      crystallize membrane proteins. Over 80% of this preparation was found to consist
      of a single protein species with a M(r) of 62,000 indicating a monomeric state.
      These data demonstrate that (i) N-terminal truncation of P450 2D6 does not
      principally interfere with heme incorporation and function of the enzyme, (ii)
      deletion of the hydrophobic N-terminus leads to a protein product which can be
      recovered largely from the soluble E. coli fraction, and (iii) this soluble
      truncated protein is highly aggregated unless detergents are added to maintain it
      in a monomeric state.

PMID- 7646053
TI  - Mechanistic studies on malate dehydrogenase from Escherichia coli.
AB  - Kinetic studies and chemical modification studies using diethylpyrocarbonate and
      iodoacetate were performed on malate dehydrogenase isolated from Escherichia
      coli. Product inhibition experiments indicate that this enzyme follows an ordered
      Bi Bi kinetic mechanism, similar to other dehydrogenases, while log V/K profiles
      reveal that one ionizing group with a pKa between 7.8 and 8.7 acts as a general
      acid/general base in the catalytic mechanism. Log V profiles indicate that malate
      binds to the correctly protonated form of the enzyme while binding of OAA is pH
      independent. Chemical modification experiments implicate an activate site
      histidine residue is essential for catalytical activity. A primary kinetic
      isotope effect of 1.44 +/- 0.14 on V/K using malate-2-d at pH 9.0 was measured
      while no isotope effect was observed on Vmax which is, again, similar to other
      dehydrogenases. This implies that proton abstraction is partially rate
      determining under nonsaturating conditions. Within experimental error, small
      isotope effects were observed on V and V/K (1.219 +/- 0.188 and 1.078 +/- 0.064,
      respectively) when NADD was utilized indicating that release of cofactor may be
      rate limiting.

PMID- 7646054
TI  - The muscle isoform of 6-phosphofructo 2-kinase/fructose 2,6-bisphosphatase of the
      teleost Sparus aurata: relationship with the liver isoform.
AB  - The liver isoform of 6-phosphofructo 2-kinase/fructose 2,6-bisphosphatase of the
      teleost fish Sparaus aurata has several characteristics similar to the skeletal
      muscle isoform of mammals. In order to ascertain the relation between muscle and
      liver isoforms in teleost, 6-phosphofructo 2-kinase/fructose 2,6-bisphosphatase
      was purified from skeletal muscle of S. aurata. The muscle isozyme is composed of
      subunits with a molecular weight of 54 kDa, is bifunctional, and has an activity
      ratio kinase to bisphosphatase of 2.5. Muscle 6-phosphofructo 2-kinase is not
      sensitive to glycerol 3-phosphate inhibition and has noncooperative KmATP, higher
      than the liver isozyme. Thus, the kinetic characteristics of the muscle were
      distinguishable from the liver isozyme. Furthermore, the muscle isozyme is not a
      substrate of cAMP-dependent protein kinase. Despite those differences, two
      polyclonal antibodies raised against purified liver and muscle isozymes from S.
      aurata are not able to distinguish between them. Both antisera recognize with
      lower affinity recombinant rat liver 6-phosphofructo 2-kinase/fructose 2,6
      bisphosphatase. A third antibody raised against the rat liver isozyme was also
      able to immunoprecipitate the teleost enzymes. The close immunological properties
      found suggest that S. aurata isozymes share epitopes in common. Considering the
      kinetic and immunological data reported, it is likely that the skeletal
      muscle/liver isozymes in teleost are products of a differentially spliced
      transcript of the same gene, as it is in rat. As those species are distant in
      vertebrate evolution, the similitude suggest that a common ancestral gene is
      involved in the muscle/liver 6-phosphofructo 2-kinase/fructose 2,6-bisphosphatase
      system in vertebrates.

PMID- 7646055
TI  - Polymerization of an Escherichia coli elongation factor Tu.
AB  - Elongation factor Tu (EF-Tu) from Escherichia coli is shown here to polymerize
      under conditions of low ionic strength and slightly acidic pH. Several factors,
      such as decreasing pH, decreasing ionic strength, increasing temperature, and
      increasing protein concentration (up to 2.5 microM) enhance the rate of
      polymerization. Both EF-Tu.GTP and EF-Tu.GDP polymerized equally well under the
      conditions studied. A lag time was observed between the lowering of the pH and
      the onset of measurable polymerization, which was not overcome by addition of
      preformed polymer "seeds." Finally, addition of unpolymerized EF-Tu.GDP to a
      solution of polymerized EF-Tu.GDP appears to lead to formation of new polymers
      instead of addition to preexisting ones, which may suggest a size limit for
      polymers of EF-Tu.GDP.

PMID- 7646056
TI  - Establishment of a recombinant hepatic cell line stably expressing alcohol
      dehydrogenase.
AB  - Hepatocytes cultured for extended periods of time lose the ability to express
      alcohol dehydrogenase and thus, the ability to efficiently oxidize ethanol.
      Therefore, it has been difficult to investigate the effects of chronic ethanol
      oxidation by hepatocytes in vitro. To circumvent this problem, we have inserted
      the coding region of an exogenous alcohol dehydrogenase gene into an hepatic cell
      line. Using the human hepatocellular carcinoma cell line, Hep G2, we have
      constructed an hepatic cell line that stably expresses alcohol dehydrogenase.
      These recombinant cells, termed HAD 73.1 cells, express approximately 40% of the
      alcohol dehydrogenase activity of freshly isolated rat hepatocytes. When the
      ethanol metabolizing ability of these cells was directly measured, the results
      indicated that not only were these cells able to metabolize ethanol at
      approximately 70% of the rate of freshly isolated rat hepatocytes but
      acetaldehyde concentrations of up to 50 microM were detected in the medium.
      Furthermore, the level of acetaldehyde produced during ethanol oxidation was
      augmented by cyanamide, an inhibitor of acetaldehyde oxidation, while the ability
      of these cells to metabolize ethanol was inhibited by pyrazole, an inhibitor of
      alcohol dehydrogenase. These results suggest that this in vitro system will be a
      valuable tool enabling detailed biochemical studies exploring the effects of
      chronic ethanol oxidation on the liver and the mechanisms of alcohol-induced
      hepatic cell injury.

PMID- 7646057
TI  - DL-beta,beta-difluoroglutamic acid mediates position-dependent enhancement or
      termination of pteroylpoly(gamma-glutamate) synthesis catalyzed by
      folylpolyglutamate synthetase.
AB  - Poly(gamma-glutamylation) of glutamate (L-Glu)-containing antifolates and natural
      folates is important in pharmacological mechanisms and in physiological
      processes. Based on previous work from our laboratories, we hypothesized that
      replacement of the L-Glu moiety in parent molecules with DL-beta,beta
      difluoroglutamic acid (DL-beta,beta-F2Glu) might be a generic means of increasing
      polyglutamylation by both increasing the synthesis rate and decreasing the
      degradation rate (J. J. McGuire et al., J. Biol. Chem. 265, 14073-14079 (1990));
      thus biological potency might be increased without other biochemical properties
      being altered. DL-beta,beta-F2Glu, synthesized by an improved route (B. P. Hart
      and J. K. Coward, Tetrahedron Lett. 34, 4917-4920 (1993)), has been incorporated
      into a methotrexate (MTX) homolog, beta,beta-difluoromethotrexate (beta,beta
      F2MTX), and a folic acid (PteGlu) homolog, beta,beta-difluorofolic acid
      (beta,beta-PteF2Glu). Biochemical properties of beta,beta-F2MTX (e.g., inhibition
      of isolated dihydrofolate reductase, transport in whole cells) are similar to
      those of MTX except that, in accord with our hypothesis, apparent substrate
      efficiency for rat and human folylpolyglutamate synthetase (FPGS) is 4- to 7.5
      fold higher, respectively, for beta,beta-F2MTX than for MTX. Analysis of the
      products synthesized by purified FPGS, however, suggests that while addition of
      the first gamma-Glu to beta,beta-F2MTX is highly efficient, subsequent additions
      occur at a negligible rate; this premise was confirmed by directly comparing the
      in vitro FPGS substrate activity of MTX-gamma-Glu and beta,beta-F2MTX-gamma-Glu.
      Furthermore, the dramatically diminished in vitro growth inhibitory potency of
      beta,beta-F2MTX as compared to MTX when exposure time to drug is decreased
      (despite otherwise similar biochemical properties) suggests that
      polyglutamylation is also impaired in intact cells. Similar results with FPGS
      have been obtained with oxidized and reduced forms of beta,beta-PteF2Glu. These
      data suggest that the effect of beta,beta-F2Glu on polyglutamylation by FPGS is
      dependent on its position relative to the point of L-Glu ligation. When beta,beta
      F2Glu is the acceptor amino acid (i.e., point of attachment), ligation of Glu is
      enhanced; however, if beta,beta-F2Glu is one residue distal to the acceptor amino
      acid, further elongation is blocked.

PMID- 7646059
TI  - Enzymatic activities of rat liver cytosol 10-formyltetrahydrofolate
      dehydrogenase.
AB  - 10-Formyltetrahydrofolate dehydrogenase (10-FTH-FDH: EC 1.5.1.6) catalyzes the
      NADP(+)-dependent oxidation of 10-formyltetrahydrofolate (10-HCO-H4PteGlu) to
      tetrahydrofolate (H4PteGlu) and CO2 and the NADP(+)-independent hydrolytic
      cleavage of 10-HCO-H4PteGlu to H4PteGlu and formate. 10-FTHFDH has a 485 amino
      acid domain at the C-terminus which is 46% identical to aldehyde dehydrogenase
      (ALDH: EC 1.2.1.3) and contains a conserved active site cysteine (Cys-707). 10
      FTHFDH catalyzed NADP(+)-dependent oxidation of propanal and the hydrolysis of p
      nitrophenyl acetate (pNPA) in a similar fashion to ALDH. Initial rate studies
      gave Km values of 46 and 636 microM, respectively, for NADP+ and propanal, while
      pNPA had a Km of 220 microM. Propanal was able to compete with 10-HCO-H4PteGlu
      for NADP(+)-dependent oxidation but had no effect on the NADP(+)-independent
      hydrolase reaction. N-Ethylmaleimide inhibited NADP(+)-dependent 10-HCO-H4PteGlu
      oxidation but only partially inhibited (65%) hydrolase activity. Disulfiram, a
      potent inhibitor of cytosolic ALDH, inhibited NADP(+)-dependent propanal
      oxidation by 10-FTHFDH. We propose that the dehydrogenase reaction of 10-FTHFDH
      has a mechanism which proceeds through thiohemiacetal and thioester
      intermediates, similar to that described for aldehyde dehydrogenase. 10-FTHFDH
      hydrolase activity was dependent on 2-mercaptoethanol and is probably an artifact
      of the assay system. The N-terminal domain of 10-FTHFDH shows identity to
      glycinamide ribonucleotide transformylase (EC 2.1.2.2) and contains a putative 10
      HCO-H4PteGlu binding site but shows no GAR-TF activity. NADP(+)-dependent
      oxidation of 10-HCO-H4PteGlu by 10-FTHFDH was inhibited by the folate anti
      metabolite, 5,10-dideazatetrahydrofolate, a known GAR-TF inhibitor.

PMID- 7646058
TI  - Regulation of rat alcohol dehydrogenase by cyclic AMP in primary hepatocyte
      culture.
AB  - Alcohol dehydrogenase (ADH) is enhanced separately by epinephrine and by glucagon
      in primary rat hepatocyte culture. This study determined whether cyclic AMP, a
      common mediator for some of the actions of the above hormones, increases ADH.
      Administration of theophylline, a cyclic AMP phosphodiesterase inhibitor which
      increases endogenous cyclic AMP, in a dose of 100 mg/kg to rats for 5 days,
      increased ADH activity. Dibutyryl cyclic AMP (10 microM) added to primary
      hepatocytes in culture increased ADH mRNA and ADH activity at 12 and 24 h,
      respectively, after its addition. The increase in ADH mRNA was preceded by an
      increase in the expression of C/EBP beta mRNA and in C/EBP beta protein.
      Dibutyryl cyclic AMP, in transient transfection experiments of primary rat
      hepatocyte culture, activated an ADH promoter gene construct containing the C/EBP
      binding site, but failed to activate a construct containing a 4-bp mutation at
      this site. These results show that cyclic AMP induces ADH and suggests that this
      effect is mediated by C/EBP beta binding to the C/EBP site. The previously
      demonstrated induction of ADH by epinephrine and glucagon may be mediated by a
      common pathway via an increase in cyclic AMP.

PMID- 7646060
TI  - Cloning, DNA sequencing, and amino acid sequencing of catechol 1,2-dioxygenases
      (pyrocatechase) from Pseudomonas putida mt-2 and Pseudomonas arvilla C-1.
AB  - Catechol 1,2-dioxygenase catalyzes the oxygenative ring cleavage of catechol to
      form cis,cis-muconic acid and is encoded by a catA gene. We have cloned a catA
      gene from Pseudomonas putida mt-2 using a PCR product of amino acid sequence
      based primers as a probe. The amino acid sequence deduced from the 930
      nucleotides was in complete agreement with the chemically determined sequence of
      the protein. Crude extracts of Escherichia coli cells carrying the catA gene
      downstream from the lac promoter showed the enzyme activity. By using the same
      probe, we also cloned and sequenced the catA beta gene for catechol 1,2
      dioxygenase isozyme beta beta from Pseudomonas arvilla C-1, which has three
      isozymes, alpha alpha, alpha beta, and beta beta (C. Nakai, H. Horiike, S.
      Kuramitsu, H. Kagamiyama, and M. Nozaki, 1990, J. Biol. Chem. 265, 660-665).
      There was very high homology between isozyme beta beta of the C-1 strain and the
      enzyme of the mt-2 strain in both the amino acid (98%) and the DNA sequences
      (97%). A preference for the use of codons terminating in C and G was found in the
      coding region of both the enzymes, which contributed to the high G + C content
      (65-66%) of the genes. A comparison of the DNA sequences of various catA genes
      from other sources revealed their common ancestry, whereas a comparison of the
      amino acid sequences of the enzymes revealed clear reflection of substrate
      specificity. Tyrosyl and histidyl residues for proposed ligands of ferric ion are
      conserved in all catechol 1,2-dioxygenases.

PMID- 7646061
TI  - Production of nitric oxide and other iron-containing metabolites during the
      reductive metabolism of nitroprusside by microsomes and by thiols.
AB  - Sodium nitroprusside is used as a hypotensive agent because of its ability to
      produce nitric oxide (NO), although direct demonstration of this has not been
      reported in a biological system. Nitroprusside (NP) nitroxide radical anion, the
      first reduction product of NP generated in the presence of microsomes and NADPH,
      was found to undergo further metabolism. One of the products produced during this
      reductive metabolism was shown to be NO. By using N-methylglucamine
      dithiocarbamate-FeCl2 complex [(NMGD)2Fe(II)] as the NO trap, we have detected
      and characterized the mononitroso bis(N-methylglucamine dithiocarbamato) iron
      (II) complex (MNBI) (g = 2.040, and A(14N) = 13.3 G) as the product of NO
      trapping. The production of NO during the reductive metabolism of NP by
      submitochondrial particles and a human HepG2 hepatoblastoma cell line was also
      demonstrated using (NMGD)2Fe(II). In addition to MNBI, two other mononitrosyl
      iron complexes, the NP nitroxide radical anion and a second species designated as
      Fe(NO)(X)(Y) (g = 2.032, and A(14N) = 14.3 G), and additional unidentified
      paramagnetic products containing iron were also detected. Thiol compounds such as
      glutathione, cysteine, and cysteamine reduce NP to generate NP nitroxide radical
      anion and a paramagnetic species characterized as a dithiolated dinitroso iron
      complex (DDIC), Fe(NO)2(RS)2 g = 2.030, A(14N) = 2.2 G(2N), and A(1H) = 1.1
      G(4H). At 77 K, DDIC generated from cysteine and NP has an axial symmetry, with g
      perpendicular = 2.040, and g parallel = 2.014. Two additional paramagnetic
      products, designated as species C (g = 2.020, linewidth = 4.8 G) and species D (g
      = 2.008, linewidth = 6.1 G), were also formed during NP reduction by thiol
      compounds. The characterization of these complexes has been hampered by the lack
      of hyperfine features in the ESR spectra. The production of NO during cysteamine
      reduction of NP was demonstrated by using (NMGD)2-Fe(II) as the spin-trap. These
      results directly demonstrate the production of NO during the reduction of NP by
      microsomes plus NADPH or by thiols. (NMGD)2-Fe(II) is a particularly useful spin
      trap for the detection of NO in a strong reducing environment.

PMID- 7646063
TI  - Metabolism of leukotriene B4 in cultured hepatoma cells.
AB  - Incubation of leukotriene B4 (LTB4) with Hep G2 cells (a human-derived hepatoma
      cell line) resulted in the production of several metabolites indicative of
      alternative pathways of LTB4 metabolism not previously observed in normal
      hepatocytes. The major extracellular LTB4-derived metabolites were structurally
      identified using mass spectrometry and ancillary techniques including
      electrospray ionization. The major metabolite was 10-hydroxy-4,6,8,12
      octadecatetraenoic acid (10-HOTE), an unexpected metabolite which lost the
      hydroxy group at carbon 5 from the parent LTB4. Two other major metabolites were
      3(R)-hydroxy-LTB4 and 3(S)-hydroxy-LTB4. The formation of these three metabolites
      revealed that beta-oxidation from the carboxyl terminus can be a significant
      metabolic pathway for degradation of this hydroxy unsaturated fatty acid. The
      normal hepatocyte LTB4-derived metabolite, 20-carboxy-LTB4, was observed as only
      a minor product. The metabolic profile for Hep G2 cells suggests that the
      efficient cytochrome P-450 pathway involved in omega-oxidation in typical
      hepatocytes is absent in these cells. Several minor metabolites were also
      identified which included dihydro products resulting from metabolism by a 12
      hydroxydehydrogenase/delta 10-reductase pathway. The formation of the major
      metabolite reveals the operation of steps in beta-oxidation of hydroxy,
      unsaturated fatty acids not anticipated by previously identified steps of fatty
      acid beta-oxidation.

PMID- 7646062
TI  - Divergent N-terminal regions in AMP deaminase and isoform-specific catalytic
      properties of the enzyme.
AB  - AMP deaminase (AMPD) catalyzes the hydrolytic deamination of AMP to IMP and NH3.
      This activity is represented throughout mammalian tissues and cells by at least
      three isoforms. Human AMPD cDNAs have been cloned and sequenced, leading to
      predictions that each isoform contains distinct amino-ends (N-terminal regions)
      in contrast to their highly conserved carboxyl-ends (C-terminal regions). Wild
      type, truncated, and chimeric human AMPD1 (isoform M) and AMPD2 (isoform L) cDNAs
      were expressed and the resultant activities partially characterized as a means to
      examine the role of divergent N-terminal regions in these polypeptides (residues
      1-262 and 1-258 of isoforms M and L, respectively) on isoform-specific catalytic
      properties. Similar to activities purified from human tissues, in the presence of
      monovalent cation, wild type isoform M displayed hyperbolic kinetics in the
      presence and absence of ATP, whereas wild type isoform L exhibited allosteric
      activation in the presence of this nucleotide effector. Expression of both a
      chimeric M (5'-AMPD1)/L (3'-AMPD2) construct and one in which the N-terminal
      region of isoform L was deleted produced activities that were also allosterically
      regulated by ATP. However, no AMPD activity was detectable following expression
      of either a chimeric L (5'-AMPD2)/M (3'-AMPD1) construct or one in which the N
      terminal region of isoform M had been deleted. The N-terminal region also
      affected the relative ability of each recombinant AMPD activity to deaminate
      substrate analogs modified in either the sugar or the phosphate, but not in the
      purine base, moieties of AMP. These combined data show (i) that isoform M, but
      not isoform L, absolutely requires its N-terminal region for proper function,
      (ii) that the C-terminal region of isoform L is responsible for allosteric
      activation by ATP, (iii) an effect of the N-terminal region on substrate-enzyme
      interaction, a contention that is discussed in context with available information
      regarding the related purine catabolic activity, adenosine deaminase.

PMID- 7646064
TI  - Steviol and steviol-glycoside: glucosyltransferase activities in Stevia
      rebaudiana Bertoni--purification and partial characterization.
AB  - The leaves of Stevia rebaudiana Bertoni contain sweet compounds which are
      glycosides of diterpene derivative steviol (ent-13-hydroxykaur-16-en-19-oic
      acid). Its main constituents are stevioside (triglucosylated steviol; 13-O-beta
      sophorosyl-19-O-beta-glucosyl-steviol) and rebaudioside-A (tetraglucosylated
      steviol; 2'-O-beta-glucosyl-13-O-beta-sophorosyl-19-O-beta-glucosyl-stev iol).
      From the extracts of S. rebaudiana Bertoni, two glucosyltransferases (GTases I
      and IIB) acting on steviol and steviol-glycosides were isolated, and another
      distinct activity (GTase IIA) acting on steviol was detected. Purified GTase I
      (subunit M(r) 24,600) catalyzed glucose transfer from UDP-glucose to steviol and
      steviolmonoside (steviol-13-O-glucopyranoside), but not to other steviol
      glycosides. Apparent Km values were 71.4 microM for steviol and 360 microM for
      UDP-glucose. GTase IIB (subunit M(r) 30,700) showed a broad substrate
      specificity, acting on steviol, steviolmonoside, steviolbioside (13-O-beta
      sophorosyl-steviol), and stevioside. Apparent Km values were 182 microM for
      steviol, 44 microM for steviolbioside, 95 microM for stevioside, and 385 microM
      for UDP-glucose. The two enzymes had a similar optimum pH at 6.5. They also acted
      effectively on ubiquitous flavonol aglycones, quercetin, and kaempferol and
      utilized kaempferol at a higher rate than steviol and steviol-glycosides. The
      apparent Km values of GTase I and IIB for kaempferol were 12 and 31 microM,
      respectively.

PMID- 7646065
TI  - Enzymes of B-ring-deoxy flavonoid biosynthesis in elicited cell cultures of "old
      man" cactus (Cephalocereus senilis).
AB  - Elicited cell cultures of the cactus Cephalocereus senilis produce a group of
      flavonoids with unsubstituted B-rings, including an aurone which represents a new
      class of phytoalexin. Preliminary enzymological studies indicated that the
      chalcone synthase (CHS) and chalcone isomerase (CHI) from cultures of C. senilis
      were active with cinnamoyl-CoA and 2',4',6'-trihydroxychalcone, respectively,
      probable intermediates for synthesis of flavonoids with unsubstituted B-rings. We
      now demonstrate that the cultures contain two isoforms of CHI, both of which are
      induced by elicitor treatment and are active with both 2',4,4',6'-tetrahydroxy-
      and 2',4',6'-trihydroxychalcone. (Hydroxy)-cinnamate:CoA ligase in the cactus
      cultures was active with cinnamic, 4-coumaric, caffeic, ferulic, and 4
      methoxycinnamic acids, but not sinapic acid. A single form of CoA ligase, as
      resolved by chromatofocusing analysis, was active against both cinnamate and 4
      coumarate. Cinnamic acid 4-hydroxylase (CA4H) activity was induced by elicitor
      treatment. Thus, elicited cultures contain the necessary enzymatic activities for
      synthesis of B-ring-hydroxy and -deoxy flavonoids. Synthesis of only the deoxy
      class in response to elicitation may result from some form of metabolic
      compartmentation through which the CA4H reaction is bypassed, leading to
      formation of cinnamoyl CoA which may then be incorporated into B-ring deoxy
      flavonoids via nondiscriminating CHS and CHI activities.

PMID- 7646066
TI  - Different response of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-sensitive genes
      in human breast cancer MCF-7 and MDA-MB 231 cells.
AB  - Human breast cancer cell lines are widely used to study the antiestrogenic effect
      of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in vitro. Like other groups we
      found that 10 nM TCDD inhibits cell growth and induces cytochrome P450 1A1
      (CYP1A1)-associated 7-ethoxyresorufin-O-deethylase (EROD) activity in MCF-7 cells
      expressing the estradiol receptor (ER). Neither cell growth nor EROD activity was
      affected in ER-negative MDA-MB 231 cells. Results of reverse transcription
      polymerase chain reaction (RT-PCR) revealed a strong induction of CYP1A1 mRNA in
      MCF-7 but only a weak increase in MDA-MB 231 cells treated with 1, 10, or 100 nM
      TCDD. Transcripts of CYP1B1 were detected in both cell lines and mRNA content was
      enhanced 8- and 30-fold in MCF-7 and MDA-MB 231 cells treated with 1 nM TCDD,
      respectively. In gel mobility shift assay a stronger signal of DNA-binding aryl
      hydrocarbon receptor (AhR) was observed in MDA-MB 231 than in MCF-7 cells treated
      with 10 nM TCDD. These results were confirmed by RT-PCR analyses which showed an
      approximately 40-fold higher AhR mRNA content in untreated MDA-MB 231 than in MCF
      7 cells. In contrast the mRNA of the AhR nuclear translocator was expressed in a
      similar range of magnitude. Treatment of the cells with TCDD did not change mRNA
      expression of both genes. Analysis of NADPH:quinone oxidoreductase (NMO-1) and
      plasminogen activator inhibitor-2 (PAI-2) mRNA expression revealed a dose
      dependent induction of both genes in MDA-MB 231 cells after TCDD-treatment. From
      the results it was concluded that AhR-mediated transactivation is not impaired in
      ER-negative MDA-MB 231 cells. In addition, the results confirm reported data that
      expression of ER seems to be important for regulation of CYP1A1 induction after
      TCDD in human breast cancer cell lines but the present data show that ER does not
      appear to have a function in TCDD-induced mRNA expression of CYP1B1, NMO-1, and
      PAI-2 in MDA-MB 231 cells.

PMID- 7646067
TI  - Residues putatively involved in binding of ATP and glucose 6-phosphate to a
      mammalian hexokinase: site-directed mutation at analogous positions in the N- and
      C-terminal halves of the type I isozyme.
AB  - Despite extensive sequence similarity between the N- and C-terminal halves of the
      Type I isozyme of mammalian hexokinase (ATP:D-hexose 6-phosphotransferase; EC
      2.7.1.1), they are functionally distinct, the C-terminal half being responsible
      for catalysis and the N-terminal half thought to play a regulatory role. We have
      examined the effects of several site-directed mutations on kinetic and regulatory
      properties of the rat Type I isozyme. Mutation of the C-terminal residues, Asp
      532 to Asn, Arg 539 to Met, and Gly 896 or Gly 898 to Val, resulted in drastic
      loss of catalytic activity (< 10% of wild-type enzyme), consistent with previous
      suggestions that these residues are involved in binding of ATP. Mutation of the
      corresponding residues in the N-terminal half of the enzyme caused much less
      marked (> 50% of wild type), but significant, effects on activity which are
      presumed to result from subtle effects on conformation of the enzyme. Mutation of
      Lys 899 to Met resulted in an approximately 50% decrease in specific activity and
      an approximately fivefold increase in the Km for ATP, consistent with the view
      that Lys 899 participates in binding of ATP through electrostatic interactions
      with the phosphate sidechain. Cys residues corresponding to Cys 158 and Cys 606
      of Type I hexokinase are found in other hexokinases that exhibit marked
      sensitivity to inhibition by the product, glucose 6-phosphate (Glc-6-P), but
      analogous residues are not found in hexokinases insensitive to Glc-6-P. However,
      this correlation appears to be coincidental since neither the mutation of Cys 158
      or Cys 606 to Ala nor any of the other mutations examined abolished sensitivity
      of Type I hexokinase to inhibition by the Glc-6-P analog 1,5-anhydroglucitol-6-P
      or to antagonism of this inhibition by P(i).

PMID- 7646068
TI  - Detergent solubilization of membrane-bound methane monooxygenase requires
      plastoquinol analogs as electron donors.
AB  - Quinols can provide reducing equivalents for the membrane-bound form of methane
      monooxygenase (pMMO), substituting for NADH in whole cells and membranes.
      Furthermore, quinols are effective reductants for the detergent-solubilized
      enzyme, whereas NADH is ineffective. The decyl analog of plastoquinol and
      duroquinol (2,3,5,6-tetramethylbenzoquinol) provide the greatest methane
      monooxygenase activity in whole cells and membrane suspensions, as well as
      detergent-solubilized samples. Lauryl maltoside is by far the best detergent for
      solubilization of catalytically active methane monooxygenase. Optimal pMMO
      activity in the detergent-solubilized fraction is obtained with a ratio of
      approximately 1.7 mg of detergent per milligram of membrane protein, independent
      of protein concentration. The detergent-solubilized pMMO retains its sensitivity
      to inhibition by cyanide, acetylene, and EDTA. It is also stimulated by exogenous
      copper, as in isolated membrane fractions. Reaction of the detergent-solubilized
      enzyme with [14C]acetylene results in labeling of a 26-kDa peptide, analogous to
      the behavior observed for isolated membrane suspensions. The selectivity of pMMO
      for duroquinol and decyl-plastoquinol, relative to other structurally similar
      quinols, suggests that the enzyme obtains reducing equivalents directly from a
      quinol (probably plastoquinol) in vivo.

PMID- 7646069
TI  - A comparative study of Na+/K(+)-ATPases of duck salt gland and canine kidney:
      implications for the enzyme's reaction mechanism.
AB  - Highly purified preparations of duck salt gland and canine kidney Na+/K(+)
      ATPases with comparable specific activities were used to clarify the causes of
      previously reported differences between the substrate-velocity curves of these
      enzymes. When assays were done under identical conditions (pH 7.4; 37 degrees C),
      and a wide range of closely spaced ATP concentrations were used, the curves of
      both enzymes exhibited intermediary plateaus, as noted before for the salt gland
      enzyme. The two enzymes also had the same numbers of phosphorylation and ouabain
      binding sites, and their catalytic subunits were of the alpha 1 isoform type as
      revealed by immunostaining with specific antibodies. The findings suggest that
      the substrate-velocity curves of all widely used Na+/K(+)-ATPases may contain an
      intermediary plateau which is diagnostic of reaction mechanisms that generate
      rate equations containing powers of substrate concentration greater than two,
      e.g., a mechanism involving an oligomer with more than two protomers.

PMID- 7646071
TI  - "Suicide" inactivation of prostaglandin I2 synthase: characterization of
      mechanism-based inactivation with isolated enzyme and endothelial cells.
AB  - "Suicide" inactivation accompanied catalysis by isolated prostaglandin I
      synthase. Inactivation occurred via a saturable, pseudo-first-order process with
      an apparent binding constant Ki = 8 microM prostaglandin H2 and an inactivation
      rate constant ki = 0.06 s-1. Enzymatic activity declined as an exponential
      function of substrate concentration and a linear function of product formation. A
      competitive inhibitor, 9,11-(methanoepoxy)-15(S)-hydroxy-prosta-5Z,13E-dienoic
      acid, protected the enzyme from inactivation. Prostaglandin H1, an endoperoxide
      which is not a substrate, inactivated the enzyme less effectively than
      prostaglandin H2. The differences between inactivation by prostaglandin H2 and
      H1, the protective effect of the competitive inhibitor, the quantitative
      similarity between Km and Ki, and the dependence on catalysis all suggest that
      inactivation originates primarily from a transition-state intermediate, not from
      malondialdehyde formed by hydrolysis of prostaglandin endoperoxides.
      Collectively, the data conform to criteria for a specific, mechanism-based
      process in which a common enzyme-substrate complex participates in two parallel
      reactions, one leading to turnover and the other to suicide inactivation.
      Inactivation accompanying catalysis by prostaglandin I synthase in intact
      endothelial cells was transient, consistent with the cellular capacity for de
      novo protein synthesis. Enzyme activity returned to the initial steady-state
      level within 15-20 min, suggesting that prostaglandin I synthase has a half-life
      < or = 5 min.

PMID- 7646070
TI  - Effects of sulfhydryl reagents, retinoids, and solubilization on the activity of
      microsomal retinol dehydrogenase.
AB  - A microsomal retinol dehydrogenase (RoDH) that recognizes holo-cellular retinol
      binding protein (CRBP) as substrate is inhibited by phenylarsine oxide (IC50 = 3
      microM) in the presence of 10 mM cysteine. Inhibition was reversible with
      dithiothreitol, indicating that two cysteine residues in close proximity are
      essential for RoDH activity. Bromophenylarsine oxide was an irreversible
      inhibitor (IC50 = 0.2 microM), suggesting that a nucleophile lies close to the
      two cysteine residues. N-Ethylmaleimide inhibited reactions supported by holo
      CRBP, but not from free retinol, suggesting that it obstructed holo-CRBP access
      to RoDH without affecting the catalytic site. RoDH activity was similar in
      microsomes from vitamin A-sufficient or vitamin A-deficient rats and was not
      inhibited by relatively high concentrations (5 microM) of all-trans-retinoic
      acid, holo-cellular retinoic acid binding protein, apo-cellular retinoic acid
      binding protein, or 9-cis-retinoic acid. Triton X-100 stimulated RoDH activity
      eightfold at a detergent to protein ratio of 0.25 to 1 (w/w). A combination of
      Tween 80, Brij 92, and Triton X-100 (2:1:2) stimulated RoDH activity eightfold at
      a detergent to protein ratio of 2.5 to 1 (w/w). Detergent-solubilized RoDH,
      partially purified through a PAO-Sepharose resin, preferred NADP(H) as cofactor,
      had a Km for retinal synthesis from holo-CRBP of 0.6 microM (Vmax = 115
      pmol/min/mg protein) and a Km for reduction of retinal bound to CRBP of 0.6
      microM (Vmax = 613 pmol/min/mg protein). This work provides further insight into
      microsomal RoDH and strengthens the evidence of an interaction between RoDH and
      holo-CRBP.

PMID- 7646072
TI  - Regulation of the activity and phosphorylation of the plasma membrane Ca(2+)
      ATPase by adriamycin in intact human erythrocytes.
AB  - We have previously shown in intact human erythrocytes that both the plasma
      membrane Ca2+ pump activity and its phosphorylation can be increased by phorbol
      12-myristate 13-acetate (PMA), a known stimulator of protein kinase C. These
      effects were inhibited by high doses of adriamycin (L. C. Wright et al., 1993,
      Arch. Biochem. Biophys. 306, 277-284). We now show that low doses of adriamycin
      (ADR) (maximum effect at 10 microM for 1-6 min) decrease the amplitude of the
      intracellular calcium ([Ca2+]i) transient induced by 2.5 microM CaCl2 and 10
      microM A23187 in intact human erythrocytes. This is reflected by a parallel
      increase in Ca(2+)-ATPase activity in plasma membranes isolated from pretreated
      intact cells. When 10 microM ADR and 1 microM PMA were combined the effects were
      additive, with a maximum decrease in the Ca2+ transient amplitude of 50%. A
      similar effect was seen on the Ca(2+)-ATPase activities in isolated membranes. In
      erythrocytes labeled with [32P]orthophosphate 10 microM ADR induced a 1.5-fold
      increase in the phosphorylation of the Ca2+ pump and when combined with 1 microM
      PMA the phosphorylation was greatly enhanced (2.3 times that induced by PMA
      alone). ADR alone and in combination with PMA was found to decrease both 32P
      labeling and lipid phosphate content of phosphatidylinositol 4,5-bisphosphate
      (PIP2). This was accompanied by an increase in the amount of 1,2-diacylglycerol
      formed in response to 10 microM ADR. We conclude that low doses of ADR are able
      to stimulate the breakdown of 6-13% of erythrocyte PIP2 by phospholipase C at an
      intracellular calcium concentration of 2.5 microM, normally regarded as below
      threshold for phospholipase C activation in erythrocytes. The diacylglycerol
      formed appears to stimulate protein kinase C to activate the Ca2+ pump and
      enhance its phosphorylation and Ca2+ efflux in intact human erythrocytes.

PMID- 7646074
TI  - Catalase degrades diperoxovanadate and releases oxygen.
AB  - On incubation with catalase diperoxovanadate was found to be degraded, showing a
      decrease in its absorbance at 356 nm and a loss of its peak with a chemical shift
      at -706 ppm in its 51V NMR spectrum. The products of the reaction had an
      absorption peak at 266 nm and chemical shifts at -569 and -578 ppm in NMR spectra
      assigned to dimer and tetramer of vanadate, respectively. Catalase released half
      the molecular equivalent of oxygen during this degradation of diperoxovanadate
      with a rate two orders of magnitude lower than that seen with H2O2. By
      substituting for and not releasing H2O2, diperoxovanadate supported scopoletin
      oxidation by horseradish peroxidase, as indicated by the reaction being not
      sensitive to catalase, unlike that seen with H2O2. Catalase-dependent oxygen
      release was sensitive to azide with both H2O2 and diperoxovanadate as substrates,
      whereas EDTA selectively inhibited this reaction with diperoxovanadate. The
      results bring out the potential of catalase in degrading diperoxovanadate and
      suggest caution in the use of this enzyme to destroy excess H2O2 during
      preparation of this compound.

PMID- 7646073
TI  - Phenobarbital induction of CYP2B1, CYP2B2, and CYP3A1 in rat liver: genetic
      differences in a common regulatory mechanism.
AB  - The phenobarbital induction of five responsive hepatic cytochrome P450 genes is
      highly strain selective, particularly in female rats (Fischer >> Wistar Furth).
      We have shown that this strain variation represents a systematic difference in
      the endocrine-mediated suppression of phenobarbital induction which points to a
      common signaling process for each of these genes. Immunoblot analysis revealed
      that the strain-specific differences of phenobarbital responsiveness (10-fold for
      CYP2B1, CYP2B2, and CYP3A1 in females) are much smaller in male animals and are
      also greatly diminished by hypophysectomy. Partial depletion of thyroid hormone
      and growth hormone levels by methimazole treatment was equally as effective as
      hypophysectomy in elevating phenobarbital-induced levels of CYP2B1, CYP2B2, and
      CYP3A1 in Wistar Furth rats, while the Fischer strain was unaffected. Ovariectomy
      suppressed the phenobarbital induction of these genes in the Wistar Furth but not
      in the Fischer strain, while castration yielded a similar differential
      suppression in male rats which was reversed by testosterone propionate
      supplementation. Changes in CYP2B1 protein closely correlated with changes in 7
      pentoxyresorufin-O-dealkylation activity, a functional marker for this P450. The
      strain-selective differences, although smaller, were also observed in the very
      low basal expression of these P450 genes, while the effects of hypophysectomy,
      ovariectomy, and castration occurred in a similar manner. However, methimazole
      was essentially ineffective relative to hypophysectomy in elevating basal
      expression of these genes. The low concentrations of residual growth hormone and
      thyroid hormone probably provide a more effective suppression in the basal than
      in the induced state. We conclude that multiple cytochrome P450 genes share a
      common phenobarbital induction pathway that, in part, alleviates the suppressive
      effects of thyroid hormone and growth hormone which are far greater in female
      Wistar Furth rats. This suppression is opposed by testosterone and to a lesser
      extent by estradiol. Similar strain differences in the endocrine control of
      weight gain point to systemic hormonal mechanisms that interface with
      phenobarbital signaling to control multiple P450 genes.

PMID- 7646075
TI  - 7-HETE, 10-HETE, and 13-HETE are major products of NADPH-dependent arachidonic
      acid metabolism in rat liver microsomes: analysis of their stereochemistry, and
      the stereochemistry of their acid-catalyzed rearrangement.
AB  - A complex profile of metabolites of [14C]arachidonic acid are formed in NADPH
      dependent reactions in liver microsomes from phenobarbital-treated rats. The
      products were resolved by HPLC and analyzed initially with an on-line diode array
      detector set to monitor 205, 220, 235, and 270 nm. In addition to the
      epoxyeicosatrienoic acids and their diol hydrolysis products, prominent
      hydroxyeicosatetraenoic acids (HETE) metabolites were identified as omega-hydroxy
      derivatives and three bis-allylic products, 7-HETE, 10-HETE, and 13-HETE. The
      formation of 13-HETE was reported by Oliw et al. (Arch. Biochem. Biophys. 300,
      434-439 (1993)). Structures of the new products were established by GC-MS, and
      for 10-HETE, by comparison to authentic synthetic material. Chiral column
      analysis indicated that 7-HETE and 10-HETE were essentially racemic. The 13-HETE
      resolved into a 40:60 ratio of 13S:13R. The bis-allylic HETEs readily undergo
      rearrangement to conjugated diene-containing HETEs in mild acidic conditions (1%
      acetic acid). Using [18O]13-HETE we observed 69% retention of the labeled oxygen
      in the 11- and 15-HETE rearrangement products. Furthermore, steric analysis of
      products from acid-treated 10-HETE and 13-HETE enantiomers revealed partial
      retention of chirality (80:20 ratio of enantiomers for methyl esters, and 60:40
      ratio for free acids) in the course of mild acid-catalyzed rearrangement. This
      represents a novel reaction of this class of arachidonic acid metabolites of
      cytochromes P450.

PMID- 7646076
TI  - Farnesyl pyrophosphate synthase from white lupin: molecular cloning, expression,
      and purification of the expressed protein.
AB  - Plants produce a variety of sesquiterpenoid compounds with diverse biological
      functions, whose synthesis is initiated by farnesyl pyrophosphate synthase [EC
      2.5.1.1, EC 2.5.1.10]. The lack of availability of molecular tools to analyze
      this enzyme has, thus far, prevented the study of its expression and regulation
      in plants. A DNA fragment corresponding to a portion of the farnesyl
      pyrophosphate synthase gene was amplified by the polymerase chain reaction using
      was amplified by the polymerase chain reaction using degenerate primers designed
      from two highly conserved domains (FLV(A/L)DD(I/M)MD and FQIQDDYLD) found in
      eukaryotic farnesyl pyrophosphate synthase sequences. A clone, pS19, of a 438-bp
      PCR fragment was used to screen a white lupin root cDNA library. Two full-length
      cDNA clones (pFPS1 and pFPS2) were isolated and sequenced, and one of them
      (pFPS2) was expressed in a bacterial system and the enzyme protein encoded by the
      clone was purified. The 1345-bp insert of pFPS2 contains a 1026-bp open reading
      frame, encoding a 342-amino-acid peptide with a calculated molecular mass of
      39,310 Da. The deduced amino acid sequence of lupin farnesyl pyrophosphate
      synthase pFPS2 shares 90 and 79% identity with those from Lupinus albus (pFPS1)
      and Arabidopsis thaliana, respectively, 51% with the yeast enzyme, and 44%
      identity with those from rat and human. The overexpressed protein, which was
      purified to near homogeneity, displayed both dimethylallyl transferase and
      geranyl transferase activities. Polyclonal antibodies raised against the purified
      protein immunorecognized a ca 39-kDa protein in lupin root extracts.

PMID- 7646077
TI  - Glycerol and lactate induce reciprocal changes in glucose formation and glutamine
      production in isolated rabbit kidney-cortex tubules incubated with aspartate.
AB  - In renal tubules isolated from fed rabbits, 1 mM aspartate is mainly utilized for
      production of glutamine, glutamate, alanine, and serine, while it is not used for
      glucose synthesis. However, the addition of either 2 mM glycerol or 2 mM lactate,
      which are poor gluconeogenic substrates in renal tubules, results in acceleration
      of both glucose formation and incorporation of [14C]aspartate into glucose by
      several fold, accompanied by about a twofold decrease in glutamine synthesis and
      marked accumulation of glutamate and alanine. Ammonium release in renal tubules
      incubated with aspartate in the presence of methionine sulfoximine, an inhibitor
      of glutamine synthetase, is also decreased on the addition of glycerol and
      lactate by about two- and threefold, respectively. Since intracellular
      [glyceraldehyde 3-phosphate]/[3-phosphoglycerate], [glycerol 3
      phosphate]/[dihydroxyacetone phosphate], [lactate]/[pyruvate], and
      intramitochondrial [glutamate]/[2-oxoglutarate] x [NH4+] ratios are increased in
      comparison with control values determined with aspartate alone, it is likely that
      the stimulatory effect of lactate and glycerol on glucose formation from
      aspartate may be due to (i) an increased availability of reducing equivalents in
      the cytosol resulting in an enhancement of glyceraldehyde-3-phosphate
      dehydrogenase activity and (ii) elevation of the mitochondrial NADH/NAD- ratio
      causing a decrease in glutamate dehydrogenase activity resulting in a diminished
      glutamine synthesis and enhanced provision of carbon skeleton of aspartate for
      gluconeogenesis. Stimulation of glucose formation in the presence of 1 mM
      aspartate + glycerol is not related to cell volume changes. However, an increase
      for about 30% of intracellular water space induced by 10 mM aspartate + glycerol
      is accompanied by both diminished gluconeogenesis and enhanced glutamine
      synthesis, compared with values measured with 1 mM aspartate plus glycerol.

PMID- 7646079
TI  - A new method of assessing rates of the futile cycle during glycolytic and
      gluconeogenic metabolism.
AB  - A method for assessing rates of the futile cycle is presented, and it is
      illustrated in vitro. Glycolytic- and gluconeogenic-type futile cycles are
      simulated for the reactions catalyzed by phosphofructokinase (EC 2.7.1.11) and
      fructose-1,6-bisphosphatase (EC 3.1.3.11) in assays systems in which the cycle
      rates in either direction can be varied and determined. While either system is
      sustaining a net flux of carbons in a given direction, the flux of radioactively
      labeled carbons in the opposite direction is determined. Different cycle rates
      are obtained by varying phosphofructokinase activity while keeping fructose-1,6
      bisphosphatase activity constant in the "gluconeogenic" simulation and varying
      fructose-1,6-bisphosphatase while keeping phosphofructokinase activity constant
      in the "glycolytic" simulation. A direct, linear relationship was found between
      the cycle rate and the radioactive labeling of fructose 1,6-bisphosphate from [U
      14C]glucose 6-phosphate during net gluconeogenic carbon flux. Also, a direct,
      linear relationship was found between cycle rate and radioactive labeling of
      fructose-6-P from [U-14C]fructose-1,6-bisP during net glycolytic carbon flux. The
      applicability, advantages, and problems of the method are discussed.

PMID- 7646078
TI  - The mRNA and the activity of lysyl hydroxylase are up-regulated by the
      administration of ascorbate and hydralazine to human skin fibroblasts from a
      patient with Ehlers-Danlos syndrome type VI.
AB  - Lysyl hydroxylase (LH) catalyzes the formation of hydroxylysine required for the
      intermolecular cross-linking of collagen, which is an essential step in collagen
      biosynthesis. Dermal fibroblasts from patients with Ehlers-Danlos Syndrome type
      VI (EDS VI), an inherited connective tissue disorder, express decreased levels of
      LH activity. In the present study we have shown that both the mRNA and the enzyme
      activity of LH in skin fibroblasts from one EDS VI patient (AT750), a compound
      heterozygote for the LH gene, are increased by administration of ascorbate and
      hydralazine, either individually or in combination. Although the AT750 cells
      express only 24% of the LH activity found in normal cells, a similar fold
      increase in activities in both EDS VI and normal cells was observed following
      treatment with ascorbate (1.5- to 2-fold) and hydralazine (2- to 4-fold), which
      paralleled the increase in their steady state LH mRNAs. Ascorbate increased total
      collagen production by 2-fold from a similar basal level of collagen synthesis in
      each cell type. This was confirmed by protein gel analysis which showed increases
      in pro alpha 1(I), pro alpha 2(I), and pro alpha 1(III) collagen chains in both
      normal and EDS VI cells. This ascorbate-mediated increase of alpha 1(I) collagen
      resulted from increased mRNAs for alpha 1(I) collagen in both cell types.
      Hydralazine treatment, with or without ascorbate, severely decreased the alpha
      1(I) collagen mRNAs in fibroblasts from both AT750 and the normal donor; total
      collagen synthesis was similarly reduced. This study shows that LH activity,
      which is severely deficient in fibroblasts from an EDS VI patient, can be
      upregulated by administration of ascorbate and hydralazine as a result of the
      increased mRNA for LH, suggesting that the mechanism for the regulation of the LH
      gene is functioning normally in this patient.

PMID- 7646080
TI  - Bacterial expression of functional membrane-bound thromboxane synthase having
      intact sequence and truncated N-terminal hydrophobic segment.
AB  - A full-length cDNA for human placental thromboxane synthase and a shortened cDNA
      lacking the sequence corresponding to the N-terminal 2-29 amino acids were
      expressed in Escherichia coli using a pCW expression vector. Both intact and
      truncated recombinant enzyme were found in the membrane fraction and were
      catalytically active. These results suggest that the N-terminal hydrophobic
      segment, a proposed membrane anchor for P-450 enzymes, is not solely responsible
      for attachment of thromboxane synthase to the membrane and is not required for
      the proper protein folding or the enzyme activity.

PMID- 7646081
TI  - The education of thoracic and cardiac surgeons: a Canadian initiative.

PMID- 7646082
TI  - Reinforced primary repair of thoracic esophageal perforation.
AB  - BACKGROUND: Treatment of esophageal perforation, especially when diagnosed late,
      remains controversial. METHODS: Twenty-eight patients were treated for thoracic
      esophageal perforation with reinforced primary repair regardless of time of
      presentation. RESULTS: Fifteen patients were treated early (< 24 hours) with no
      deaths. Two had contained postoperative leaks, which healed. Thirteen were
      treated late (mean, 5.5 days) with four deaths (3 with healed repairs).
      Postoperative leaks occurred in 7 patients; of the leaks, 4 healed, 2 became a
      controlled fistula, and 1 required reoperation. Primary healing with preservation
      of the native esophagus was achieved in 25 patients (89%). Among the 18 patients
      without evidence of sepsis preoperatively, post-operative leaks developed in 2
      (11%). Ten patients had evidence of sepsis preoperatively, and postoperative
      leaks developed in 7 (70%). CONCLUSIONS: Patients who present with sepsis have an
      increased risk of postoperative leak and therefore should have the repair
      buttressed. Overall mortality was 14% and no deaths were due to persistent leaks
      or mediastinal sepsis. Reinforced primary repair retains the native esophagus and
      avoids the need for later reconstructive operations. In the absence of a
      nondilatable stricture or cancer, reinforced primary repair should be performed
      for most thoracic esophageal perforations, early or late.

PMID- 7646083
TI  - Surgical treatment of nontumoral stenoses of the upper airway.
AB  - BACKGROUND: After 1970, the widespread use of nasotracheal intubation, avoiding
      tracheostomy and its pitfalls, resulted in more frequent laryngeal or
      laryngotracheal stenoses, which required more complex and sometimes multistaged
      procedures. METHODS: A series of 217 nontumoral stenoses of the upper airway were
      treated following the same therapeutic principles in the period 1978 to 1992. Two
      hundred one of them were iatrogenic postintubation strictures (92%); the others
      were posttraumatic (7), idiopathic (5), and various (4). RESULTS: One hundred
      twenty (55%) were tracheal stenoses and treated by resection and primary end-to
      end anastomosis with 117 excellent or good results and three deaths. Length of
      the stenosis, old age, neuropsychological sequelae, and overall poor respiratory
      status of the patients made up the remaining difficulties in the treatment.
      Ninety-seven (45%) were laryngotracheal stenoses with much more complex surgical
      indications: 57 patients underwent tracheal and subglottic resection and
      anastomosis with 56 successes and one death, 7 had laryngotracheal resection and
      anastomosis with total cricoidectomy and consequently laryngeal stenting for 3 to
      6 months (six successes, one death), 3 had supraglottic resection and anastomosis
      (three successes), 12 patients with glottic opening difficulties and short
      laryngeal stenosis underwent a laryngeal enlargement over a T tube without
      resection (11 successes, one death), and 18 were subjected to a complex
      combination of resection and modeling with 16 successes, 2 failures, and 1 death.
      Final results were successful in 208 cases (96%) with seven deaths and two
      failures. Mild phonetic sequelae were observed after laryngeal modeling. A
      minimal follow-up of 1 year has shown long-term stability of most repairs.
      CONCLUSIONS: Despite acceptable results, the therapeutic approach remains
      difficult for laryngotracheal stenoses involving the glottic and the supraglottic
      level as well as for those that have not responded to previous attempts at
      repair. In a few cases, despite a meticulous preoperative assessment, the
      surgical strategy can only be adopted intraoperatively. The key to surgical
      success is undoubtedly a careful preoperative treatment of infection and
      inflammation as well as a meticulous muco-mucosal approximation of healthy
      margins at the anastomosis.

PMID- 7646084
TI  - Esophageal replacement: gastric tube or whole stomach?
AB  - BACKGROUND: The stomach can be used either in its entirely or as a greater
      curvature tube for esophageal replacement. METHODS: The study compares the
      gastric tube (group A; n = 112) to the whole stomach whose lesser curvature is
      denuded (group B; n = 100) in terms of technical complication and alimentary
      comfort. The clinical results are substantiated by assessment of the eating
      performance of patients and control subjects at a test meal, measurement of the
      gastric dimensions before and after both tailoring procedures, and intraarterial
      staining of the gastric wall. RESULTS: Major differences between the two groups
      are cervical anastomosis stenoses (22.3% versus 6% [A versus B]; p = 0.008),
      fistulas (7.9% versus 1%; p = 0.0209), number of meals and snacks per day (4.6
      versus 4; p = 0.0275), sensation of early fullness at meals (52.4% versus 17.8%;
      p < 0.0001), ratings given to the long-term alimentary comfort (presymptomatic
      condition = 10 points) (7.6 versus 8.8 out of 10 on average; p < 0.0001), and
      calories consumed in 1 minute at a test meal (59% [p < 0.05] versus 77% of those
      consumed by control subjects). The volume of the stomach is reduced by a range of
      21.4% to 47.2% after tubulization (group A) whereas it increases by a range of
      4.9% to 17.4% after denudation of the lesser curve (group B). Intraarterial
      staining of the gastric wall reveals the poor vascularity of the upper-most
      segment of the greater curve. CONCLUSION: Slight increase of the gastric capacity
      and maintenance of the submucosal vascular network account for the better results
      achieved with the whole stomach.

PMID- 7646085
TI  - MRI complements standard assessment of right ventricular function after lung
      transplantation.
AB  - BACKGROUND: Changes in right ventricular mass and ejection fraction after single
      lung transplantation for pulmonary hypertension are poorly understood. METHODS:
      To complement functional data provided by echocardiography, radionuclide
      ventriculography, and right heart catheterization, magnetic resonance imaging was
      used to assess right ventricular function in 5 single-lung transplant recipients
      with preoperative pulmonary hypertension and right ventricular dysfunction (right
      ventricular ejection fraction, 0.21 +/- 0.09). The right and left ventricular
      mass, ejection fraction, and mass ratio (left ventricular mass/right ventricular
      mass) were calculated from the magnetic resonance images. RESULTS: The mean
      pulmonary artery pressure fell from 72 +/- 18 to 21 +/- 8 mm Hg after
      transplantation. At 3 months after transplantation both the left ventricular and
      right ventricular ejection fractions approached normal values, as shown by both
      radionuclide ventriculography and magnetic resonance imaging, but the right
      ventricular mass remained abnormally high with slightly low mass ratios. By 1
      year both the left ventricular and right ventricular masses had regressed to
      normal with near-normal mass ratios. CONCLUSIONS: Right ventricular performance
      returns to nearly normal early after transplantation, but the right ventricular
      mass regresses over a more prolonged time. Cine magnetic resonance imaging
      provides a noninvasive means of assessing changes in right ventricular function
      and mass after lung transplantation.

PMID- 7646086
TI  - Isolated thoracic duct injury after penetrating chest trauma.
AB  - BACKGROUND: Isolated thoracic duct injuries as a result of penetrating chest
      trauma without any major vascular or tracheoesophageal injury seldom are seen.
      METHODS: A retrospective 13-year review identified 8 patients with this injury.
      RESULTS: Seven had supraclavicular or suprascapular knife stabs, and the eighth
      had a low-velocity gunshot injury entering the mid-lateral right chest wall. All
      7 stab victims presented with left-sided chylothoraces, and the site of injury of
      the thoracic duct was within Poirier's triangle, the borders of which are the
      arch of aorta, the left subclavian artery, and the vertebral column as seen from
      a lateral approach. Five patients initially were treated conservatively for 13.4
      +/- 4.4 days without success. Surgical intervention thus was necessary and was
      successful in all 8 patients. The thoracic duct injury was controlled
      successfully through a left posterolateral thoracotomy in 6 patients. A
      supraclavicular repair was attempted in 1 patient but failed to control the leak
      and required reexploration via the supraclavicular approach. The right
      chylothorax from the gunshot injury was explored via a right posterolateral
      thoracotomy; the leak into the pleura was identified and obliterated.
      CONCLUSIONS: As conservative management was uniformly unsuccessful, we advocate
      early operative management through a thoracotomy on the side of the chylothorax
      for this relatively rare injury.

PMID- 7646087
TI  - Complete atrioventricular cardiac transplantation: improved performance compared
      with the standard technique.
AB  - BACKGROUND: There has been renewed clinical interest in an alternative technique
      to orthotopic cardiac transplantation involving six anastomoses: left pulmonary
      veins, right pulmonary veins, inferior vena cava, pulmonary artery, aorta, and
      superior vena cava (complete technique). In this study, the results of the
      complete technique are compared with those of the standard operation (ventricular
      transplantation with atrioplasty). METHODS: Dogs were used for ten acute standard
      and ten acute complete atrioventricular transplantations. There were no
      significant differences in the baseline cardiac function (preload-independent
      right and left ventricular recruitable stroke work), bypass times, and cardiac
      ischemic times between the two groups. RESULTS: After transplantation, sinus
      rhythm was preserved after all ten complete and after only one standard
      transplantation but no significant hemodynamic differences were observed. The
      right and left ventricular preload-independent recruitable stroke work in the
      complete group and the left ventricular preload-independent recruitable stroke
      work in the standard group were conserved after transplantation, but the right
      ventricular preload-independent recruitable stroke work decreased by 39% +/- 8%
      (p < 0.05) in the standard group. There was also a significant decrease in the
      rate of biventricular filling in the standard group after transplantation.
      CONCLUSIONS: Complete atrioventricular transplantation is a feasible alternative
      technique and conserves normal sinus rhythm. The ischemic and bypass times are
      comparable for both methods. The insignificant change in the rate of
      biventricular filling in the dogs undergoing the complete technique indicates
      right and left ventricular diastolic function may be conserved after
      transplantation.

PMID- 7646088
TI  - Mechanical ventricular assistance: an economical and effective means of treating
      end-stage heart disease.
AB  - BACKGROUND: Heightened awareness of medical costs has escalated criticism toward
      expensive medical therapy. METHODS: The use of ventricular assistance devices
      (VADs) at Pennsylvania State University as a bridge to transplantation was
      reviewed. Records of 43 patients listed as status 1 from July 1991 to July 1994
      were compared. RESULTS: This analysis demonstrated that for all patients treated
      with the intent to transplant, those who were bridged with a VAD exhibited a
      trend toward an improved transplantation rate (92% versus 68%) and a
      significantly greater rate of discharge from the hospital (92% versus 55.4%; p =
      0.023) than the medically managed patients. Although overall charges and costs
      were higher in VAD-supported patients, this was related to significantly longer
      pretransplantation hospitalization. When normalized to daily costs and charges,
      this discrepancy in expenses was eliminated. CONCLUSIONS: The superior rate of
      discharge at equitable daily costs and charges for the VAD patients draws
      continued enthusiasm toward use of these devices as a bridge to transplantation.
      Furthermore, development of outpatient care for VAD-supported patients and
      continued advances in the use of these devices may further reduce the cost of
      managing these critically ill patients.

PMID- 7646089
TI  - 3,5,3' Triiodo-L-thyronine pretreatment with cardioplegic arrest and chronic left
      ventricular dysfunction.
AB  - BACKGROUND: The active form of thyroid hormone, T3, may be an important
      determinant of left ventricular (LV) function after hypothermic cardioplegic
      arrest and rewarming, particularly in patients with preexisting LV dysfunction.
      Thus, the present project tested the hypothesis that T3 pretreatment will improve
      myocyte contractile performance after hypothermic cardioplegic arrest and
      rewarming in the setting of chronic LV dysfunction. METHODS: Control LV porcine
      myocytes (n = 160) and cardiomyopathic LV (rapid pacing for 3 weeks at 240
      beats/min) myocytes (n = 100) were treated with or without 80 pmol/L T3. Myocytes
      then were maintained in normothermic conditions (2 hours at 37 degrees C in
      media) or exposed to hypothermic cardioplegic arrest ([K+], 24 mmol/L; 2 hours at
      4 degrees C) with subsequent rewarming. RESULTS: After cardioplegic arrest and
      rewarming, T3 pretreatment increased myocyte velocity of shortening by 41% in
      control myocytes and by 35% in cardiomyopathic myocytes when compared to
      untreated myocytes. Furthermore, T3 pretreatment followed by beta-adrenergic
      receptor stimulation with isoproterenol (25 nmol/L) improved myocyte velocity of
      shortening by 24% in control myocytes and 90% in cardiomyopathic myocytes after
      hypothermic cardioplegic arrest and rewarming, as compared with untreated
      myocytes. CONCLUSIONS: In summary, this study provides evidence to suggest that
      preemptive treatment with T3 may improve LV pump function and beta-adrenergic
      responsiveness after hypothermic cardioplegic arrest and rewarming in patients
      with underlying LV dysfunction.

PMID- 7646090
TI  - Nitric oxide is superior to prostacyclin for pulmonary hypertension after cardiac
      operations.
AB  - BACKGROUND: Severe pulmonary hypertension is still a cause of morbidity and
      mortality in children after cardiac operations. The objective of this study was
      to compare the vasodilator properties of inhaled nitric oxide, a novel pulmonary
      vasodilator, and intravenous prostacyclin in the treatment of severe
      postoperative pulmonary hypertension. METHODS: Thirteen children (aged 3 days to
      12 months) with severe pulmonary hypertension after cardiac operations were given
      inhaled nitric oxide (20 ppm x 10 minutes) and intravenous prostacyclin (20 ng.kg
      1.min-1 x 10 minutes) in a prospective, randomized cross-over study. RESULTS:
      Both nitric oxide and prostacyclin resulted in a reduction in pulmonary arterial
      pressure, although the mean pulmonary arterial pressure was significantly lower
      during nitric oxide therapy (28.5 +/- 2.9 mm Hg) than during prostacyclin therapy
      (35.4 +/- 2.1 mm Hg; p < 0.05). The mean pulmonary to systemic arterial pressure
      ratio was also significantly lower during nitric oxide than prostacylin
      administration (0.46 +/- 0.04 versus 0.68 +/- 0.05; p < 0.01), due mainly to only
      prostacyclin lowering systemic blood pressure. CONCLUSIONS: Inhaled nitric oxide
      was a more effective and selective pulmonary vasodilator than prostacyclin and
      should be considered as the preferred treatment for severe postoperative
      pulmonary hypertension.

PMID- 7646091
TI  - Safety and efficacy of concomitant carotid and coronary artery operations.
AB  - BACKGROUND: Controversy exists concerning the best management for patients with
      concurrent severe carotid and coronary artery disease. METHODS: The records of
      200 consecutive patients having concurrent carotid endarterectomy and coronary
      artery bypass grafting from 1979 to 1993 were reviewed, and follow-up was
      obtained (99% complete). Of the group (77% male; mean age, 67 years), 134 (67%)
      had unstable angina, 130 (65%) had triple-vessel disease, and 86 (43%) had left
      main coronary stenosis. Preoperative investigation revealed asymptomatic bruits
      in 116 (58%), transient ischemia in 65 (32%), strokes in 31 (16%), and bilateral
      carotid disease in 44 patients (22%). Nonelective operations were required in 66
      patients (33%). RESULTS: Hospital death occurred in 7 patients (3.5%), myocardial
      infarction in 5 (2.5%), and permanent stroke in 6 (3%). Ten-year actuarial event
      free rates were as follows: death, 58%; myocardial infarction, 81%; stroke, 92%;
      percutaneous angioplasty, 98%; redo coronary artery grafting, 94%; and all
      morbidity and mortality, 56%. Significant multivariate predictors of hospital
      death were postoperative stroke, failure to use an internal mammary artery graft,
      intraoperative intraaortic balloon, and nonelective operation. Significant
      predictors of postoperative stroke were peripheral vascular disease and unstable
      angina. Significant predictors of prolonged hospital stay were postoperative
      stroke, advanced age, and nonelective operation. CONCLUSIONS: Concomitant carotid
      endarterectomy and coronary bypass grafting can be performed with acceptably low
      operative risk and good long-term freedom from coronary and neurologic events.

PMID- 7646092
TI  - Retrograde cerebral perfusion does not perfuse the brain in nonhuman primates.
AB  - BACKGROUND: Recently retrograde cerebral perfusion (RCP) has been advocated as an
      alternative to complete circulatory arrest during aortic arch surgery. METHODS:
      In 19 baboons, we compared brain protection using hypothermic circulatory arrest
      or RCP. Animals were placed on cardiopulmonary bypass, cooled to 18 degrees C,
      underwent 1 hour of circulatory arrest or RCP, and were reperfused for 3 hours.
      Biochemical variables, cerebral blood flow (colored microsphere technique), and
      brain histology were assessed. RESULTS: Release of the brain-specific ischemic
      marker CK-BB was similar in both groups (peak values, 123 +/- 97 U/L in the
      circulatory arrest group and 164 +/- 88 U/L in the RCP group; p > 0.05), as were
      the arteriovenous differences in glucose uptake and lactate production (p >
      0.05). During RCP, significant brain flow could not be detected (0.5 +/- 0.5
      mL.min-1 x 100 g-1). About 90% of the blood was shunted to the inferior caval
      vein, and an equilibrium in circulating microspheres was found between RCP inflow
      and caval vein outflow. Less than 1% of the RCP inflow returned to the aortic
      arch. Histologic signs of brain damage were minimal in both groups, although
      slightly more glial edema was found in the RCP group. CONCLUSIONS: These data
      suggest that in nonhuman primates, retrograde cerebral perfusion does not perfuse
      the brain because of venovenous shunting.

PMID- 7646093
TI  - Pediatric cardiac surgical ECMO: multivariate analysis of risk factors for
      hospital death.
AB  - BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has emerged as an
      effective technique for the mechanical support of many pediatric postcardiotomy
      patients with medically refractory cardiac failure. METHODS: We retrospectively
      reviewed the records of 73 pediatric patients with congenital heart disease who
      were placed on ECMO support between August 1984 and February 1994. The patients
      were divided into groups defined by the timing of ECMO cannulation relative to
      the time of operation. Group 1 patients (n = 7, 9.6%) were placed on ECMO
      preoperatively. Group 2 patients (n = 66, 90.4%) were a heterogeneous population
      placed on ECMO at any interval after cardiac repair. Subgroup 2A consisted of
      patients (n = 17, 25.8%) who could not be weaned from cardiopulmonary bypass and
      were converted directly to ECMO support immediately after repair. Subgroup 2B
      patients (n = 49, 74.2%) were cannulated postoperatively after an initial period
      of clinical stability. RESULTS: Hospital survival for all study patients (42/73)
      and for group 2 patients (38/66) was 58%. Only 4 group 2A patients (23.5%)
      survived their hospitalization compared with 34 group 2B patients (69.4%) (p =
      0.001). Multivariate analysis identified elevated right atrial pressure after
      ECMO decannulation (p = 0.049) and, possibly, membership in group 2A (p = 0.061)
      as independent risk factors for hospital death. CONCLUSIONS: Extracorporeal
      membrane oxygenation is most effective in salvaging pediatric cardiac surgical
      patients who demonstrate medically refractory hemodynamic deterioration at some
      interval after being successfully weaned from cardiopulmonary bypass. The right
      atrial pressure after extracorporeal membrane oxygenation decannulation is an
      independent predictor of hospital death.

PMID- 7646094
TI  - Retrograde cerebral and distal aortic perfusion during ascending and
      thoracoabdominal aortic operations.
AB  - BACKGROUND: Several alternative circulatory management techniques during thoracic
      aortic reconstruction have been implemented at this institution. This study was
      performed to assess whether retrograde cerebral perfusion during proximal aortic
      operations and distal aortic perfusion during thoracoabdominal aortic operations
      have improved outcomes. METHODS: A retrospective review of 156 patients
      undergoing elective and emergent operations of the thoracic aorta over the past 7
      years was performed. Seventy-five patients underwent proximal aortic procedures:
      22 with ascending aneurysms, 45 with type A dissections, and 8 with arch
      reconstructions. Eighty-one patients underwent descending thoracic or
      thoracoabdominal procedures: 26 with Crawford type I aneurysms, 18 with type II,
      8 with type III, 8 with type IV, 11 with traumatic transections, and 10 with type
      B dissections. Outcomes measured were neurologic injury, renal failure, and
      mortality. RESULTS: For proximal aortic procedures, the stroke rate was 12% using
      cardiopulmonary bypass and 48% using hypothermic circulatory arrest. The addition
      of retrograde cerebral perfusion decreased the stroke rate to 0% (p < 0.01) and
      the mortality rate to 7.1% compared with 37% for hypothermic circulatory arrest
      (p < 0.05). For thoracic and thoracoabdominal aortic operations, straight cross
      clamping resulted in a 27% rate of spinal cord injury and a 24% rate of renal
      failure, whereas the addition of distal aortic bypass resulted in a statistically
      significant reduction (p < 0.01) in neurologic injury to 7% and a notable, but
      not statistically significant, decrease in renal failure to 13%. Distal aortic
      bypass also reduced the mortality rate from 22% to 7% (p < 0.05). CONCLUSIONS:
      Retrograde cerebral perfusion decreases the stroke rate and mortality rate in
      proximal aortic operations and distal aortic perfusion decreases the rates of
      neurologic injury, renal failure, and mortality in thoracoabdominal aortic
      operations.

PMID- 7646095
TI  - Left atrial function after Cox's maze operation concomitant with mitral valve
      operation.
AB  - BACKGROUND: This study examined whether the atrial fibrillation that commonly
      occurs in patients with a mitral valve operation could be eliminated by a
      concomitant maze operation. METHODS: Left atrial function after Cox's maze
      operation performed concomitantly with a mitral valve operation was evaluated in
      10 patients ranging in age from 38 to 67 years (mean age, 54 years). Seven
      patients who had had coronary artery bypass grafting served as the control group.
      Using transthoracic echocardiography, the ratio between the peak speed of the
      early filling wave and that of the atrial contraction wave (A/E ratio) and the
      atrial filling fraction (AFF) were determined from transmitral flow measurements.
      These two indices have been considered to represent the contribution of left
      atrial active contraction to ventricular filling. RESULTS: The A/E ratio and the
      AFF were significantly lower in the maze group (0.35 +/- 0.17 versus 0.97 +/-
      0.28 [p < 0.01] and 17.6% +/- 8.8% versus 36.8% +/- 6.4% [p < 0.01],
      respectively). The A/E ratio and the AFF correlated inversely with age (r = 
      0.72, p < 0.05 and r = 0.76, p < 0.05, respectively) in the maze group. In an
      angiographic study, the mean left atrial maximal volume index in the maze group
      was approximately three times larger than that in the control group (117.5 +/-
      24.3 mL/m2 versus 35.3 +/- 6.6 mL/m2 [p < 0.01]). The left atrial active emptying
      volume index was significantly smaller in patients in the maze group (7.2 +/- 2.5
      mL/m2 versus 13.1 +/- 4.6 mL/m2 [p < 0.01]). CONCLUSIONS: After the maze
      procedure performed concomitantly with a mitral valve operation in patients with
      a dilated left atrium, left atrial contraction is detectable but incomplete in
      the elderly.

PMID- 7646096
TI  - Cox maze operation without cryoablation for the treatment of chronic atrial
      fibrillation.
AB  - BACKGROUND: From August 1993 to May 1994, 20 patients (mean age, 43 years) with
      atrial fibrillation underwent the maze operation without cryoablation. Ten
      patients had mitral stenosis, 5 had mitral insufficiency, and 5 had a mixed
      mitral lesion. The mean left atrial diameter as measured on echocardiograms was
      6.1 cm. The cause was rheumatic in 17 patients (85%) and degenerative in 3 (15%).
      Seven patients had had previous episodes of thromboembolism. METHODS: Mitral
      valvuloplasty was performed on 7 patients, mitral commissurotomy on 4, and mitral
      valve replacement on 9. Thrombi were found in the left atrium of 7 patients and
      also in the right atrium in 2. The mean cross-clamp time was 73 minutes (range,
      52 to 108 minutes). RESULTS: Patients were discharged from the hospital in good
      condition. Hemodynamic studies and Doppler echocardiograms showed significant
      reduction in the left atrial diameter (mean diameter, 4.9 cm; p < 0.01) in 18
      patients. The two-channel Holter monitor showed sinus rhythm in 15 patients,
      atrial ectopic rhythm in 4, and atrial fibrillation in 1. Eleven patients (55%)
      experienced atrial fibrillation (9 in the first 3 months postoperatively), which
      was reversed with quinidine. Ninety percent of patients had development of an
      effective, synchronous, atrial systole. Six to 15 months postoperatively (average
      follow-up, 10 months), all patients were in functional class I, and 18 were not
      on a regimen of antiarrhythmic medication. CONCLUSIONS: This simplification of
      the maze operation has been demonstrated to be an effective alternative for the
      treatment of chronic atrial fibrillation.

PMID- 7646097
TI  - Completely heparinized cardiopulmonary bypass and reduced systemic heparin:
      clinical and hemostatic effects.
AB  - BACKGROUND: When heparinized circuits are used for cardiopulmonary bypass, the
      amounts of heparin and protamine administered systemically can be reduced.
      However, it is not entirely known what effects this reduction in systemic
      anticoagulation has on clinical performance and on the coagulation and
      fibrinolytic systems. METHODS: Two hundred three patients undergoing first-time
      elective myocardial revascularization were prospectively randomized either to a
      group in which a completely heparin-coated circuit was used for perfusion (group
      H; n = 101 patients) and in which a reduced heparin dose was given (activated
      clotting time, > 250 seconds) or to a control group (group C; n = 102 patients)
      in which an uncoated, but otherwise identical, circuit was used and in which full
      systemic heparinization was induced (activated clotting time, > 480 seconds).
      Indicators of thrombin generation, platelet activation, and fibrinolytic activity
      were studied in a subset of 34 patients. RESULTS: The total amount of
      postoperative mediastinal drainage was significantly reduced in group H (median,
      575 mL) compared with that in group C (median, 635 mL; p = 0.002). Two patients
      in group C but none in group H received homologous red blood cell transfusions (p
      = not significant). The loss of hemoglobin in group H was a median of 21 g/L, and
      this was significantly lower than the 25 g/L noted in the control group (p =
      0.006). During cardiopulmonary bypass, the plasma levels of thrombin-antithrombin
      complex and prothrombin fragment 1.2 increased in both groups. At the end of
      cardiopulmonary bypass the plasma levels of these markers of thrombin formation
      were significantly higher in group H, although the increase was modest compared
      with the major increase observed 2 hours after operation in both groups. There
      were no significant intergroup differences in the platelet counts, the
      concentration of beta-thromboglobulin, or the plasma levels of fibrinogen and D
      dimer. No differences in perioperative morbidity, the postoperative kidney
      function, or the intubation time were observed, and there were no hospital
      deaths. CONCLUSIONS: The combination of complete heparin-coated cardiopulmonary
      bypass circuits and low systemic heparinization is safe for patients undergoing
      elective coronary artery bypass procedures and reduces the perioperative blood
      loss. There was no evidence of increased thrombogenicity, fibrinolytic activity,
      or consumption of coagulation factors. No clinical or technical side effects were
      observed.

PMID- 7646098
TI  - Antithymocyte globulin and methotrexate therapy of severe or persistent cardiac
      allograft rejection.
AB  - BACKGROUND: The treatment of severe or persistent acute rejection remains
      difficult despite newer immunosuppressive agents available. METHODS: To evaluate
      the effectiveness of rabbit antithymocyte globulin and methotrexate as therapy
      for severe or persistent acute cardiac allograft rejection, we conducted a
      retrospective analysis of clinical and laboratory data from 150 consecutive heart
      transplant recipients between 1983 and 1994. RESULTS: Thirteen episodes of severe
      or refractory acute rejection were treated with rabbit antithymocyte globulin in
      10 patients. Rabbit antithymocyte globulin (125 mg/day for 3 consecutive days)
      was effective in 90% of patients. Therapy was well tolerated, and contributed to
      one infectious complication, no malignancy, and long-term survival in 8 of 10
      patients. Recurrent rejection developed in 60% of patients. Methotrexate (7.5 to
      15 mg/wk for 16 weeks) was administered to 8 patients with persistent rejection
      documented on three consecutive endomyocardial biopsies. Therapy was effective in
      6 of the 8 patients, with one infectious complication and no malignancy on follow
      up. White blood cell count decreased significantly during therapy (p = 0.008).
      Seven of the 8 patients in the methotrexate group are long-term survivors.
      CONCLUSIONS: Rabbit antithymocyte globulin is a valuable alternative in patients
      with severe or refractory acute rejection. Methotrexate is an important adjunct
      in patients with persistent rejection unresponsive to conventional
      immunosuppressive regimens.

PMID- 7646099
TI  - Inhibition of Na+/H+ exchanger attenuates neutrophil-mediated reperfusion injury.
AB  - BACKGROUND: The effect of Na+/H+ exchange inhibition in neutrophil-induced
      reperfusion injury was investigated using a new amiloride analogue, 5-methyl-N
      isobutyl amiloride (MIA). METHODS: Rat neutrophils were separated using Percoll
      gradient. Luminol chemiluminescence intensity of isolated neutrophils was
      depressed by MIA in a dose-dependent manner. RESULTS: The effect of MIA on
      neutrophil-induced reperfusion injury was evaluated in Langendorff-perfused rat
      hearts subjected to 30 minutes of normothermic ischemia. Postischemic left
      ventricular developed pressure recovery was depressed by the reperfusion with
      neutrophils (60% +/- 7% to 33% +/- 26%) and was reverted by MIA pretreatment (86%
      +/- 17%, p < 0.05). MIA also improved percent recovery of coronary flow (51% +/-
      2% to 70% +/- 13%), reduced creatine kinase (0.28 +/- 0.1 to 0.085 +/- 0.03 IU.L
      1.g-1 dry wt), and lactate dehydrogenase leakage (10.6 +/- 3.8 to 5.16 +/- 1.3
      IU.L-1.g-1 dry wt) significantly. The incidence of reperfusion-induced
      ventricular fibrillation also was reduced by MIA. CONCLUSIONS: The inhibition of
      Na+/H+ exchange shows a protective effect against neutrophil-induced reperfusion
      injury possibly by inhibiting the activation of neutrophils.

PMID- 7646100
TI  - Laparotomy after using the gastroepiploic artery graft: retrogastric versus
      antegastric route.
AB  - BACKGROUND: Most cardiac surgeons prefer the antegastric route for the right
      gastroepiploic artery (RGEA) graft. When placed anterior to the stomach, the RGEA
      pedicle may adhere to the greater omentum, or to the anterior abdominal wall, and
      may be injured during future abdominal operations. METHODS: To avoid this
      potentially lethal complication, we prefer to place the RGEA graft behind the
      stomach and the left lobe of the liver. In our experience with 144 patients in
      whom the retrogastric route was used, 7 patients required an abdominal operation
      (2 had cholecystectomy, 2 had a partial colectomy, 1 had repair of paraesophageal
      hernia, and 2 had repair of abdominal wall complications). There was no need to
      dissect the RGEA graft in any of these patients. RESULTS: There was no evidence
      of myocardial ischemia or other complications during or after the operation in
      any patient. CONCLUSIONS: Based on our experience and the fact that any injury to
      the RGEA graft may have catastrophic consequences, we strongly advocate the
      retrogastric route to minimize the risk of injury to the RGEA graft during a
      subsequent laparotomy.

PMID- 7646101
TI  - Sternal traction after open heart operation: an effective alternative to delayed
      sternal closure.
AB  - BACKGROUND: Routine closure of the sternum after cardiovascular surgical
      procedures sometimes causes severe cardiac depression because of a tamponade-like
      reduction in ventricular filling, leading to cardiogenic shock. Leaving the
      sternal halves apart, sealing the mediastinum by simply approximating the skin or
      using a prosthetic patch, and then performing delayed sternal closure in several
      days is a widely practiced life-saving maneuver. METHODS: Described herein is an
      experience with 5 patients with severe cardiac output depression of the type
      usually treated by delayed sternal closure. Instead, upward (outward) traction
      was applied to the anterior chest while the sternum was primarily closed.
      Traction was maintained with full-thickness chest wall sutures. RESULTS: The
      traction sutures were removed successfully in the intensive care unit between 1
      and 4 days postoperatively, after appropriate vigorous treatment of postbypass
      myocardial enlargement and pulmonary distention and edema. CONCLUSIONS: This
      method of sternal traction allows physiologic improvement equivalent to delayed
      sternal closure in some patients and obviates the need for returning to the
      operating room to close the sternum in the early postoperative period.

PMID- 7646102
TI  - Left ventricular assistance with the transthoracic 24F Hemopump for recovery of
      the failing heart.
AB  - BACKGROUND: The Hemopump was developed as a more powerful assist device for
      postcardiotomy support in patients in whom the intraaortic balloon pump is
      insufficient. METHODS: Over a 2-year period 21 (0.8%) of 2,585 patients
      undergoing cardiac operations needed a ventricular assist device because of
      postcardiotomy heart failure unresponsive to pharmacologic and intraaortic
      balloon support. Sixteen of these patients were assisted with the 24F
      transthoracic Hemopump left ventricular assist device. The aim of the mechanical
      support was myocardial recovery as the underlying conditions (age, arterial
      hypertension, diabetes, vascular and pulmonary disease) excluded heart
      transplantation. RESULTS: Hemodynamic improvement was apparent with a decrease in
      left atrial pressure (mean, 18.6 to 9.2 mm Hg), an increase in arterial blood
      pressure (mean, 54.1 to 70.1 mm Hg), and an increase in cardiac index. Five
      patients died within the first 24 hours because of low cardiac output. Although
      the heart was well unloaded (decrease in left atrial pressure of 8 +/- 4.69 mm Hg
      versus 9.3 +/- 5.51 mm Hg for the other patients), the increase in cardiac index
      was significantly lower (+0.516 versus +1.377 L.min-1.m-2; p = 0.027). Three of
      these 5 patients were known to have severe left ventricular hypertrophy. Of the
      remaining 11 patients, 2 were assisted for 1 week but failed to show recovery of
      the myocardium, 8 (50%) were weaned, and 4 (25%) were discharged. There were no
      device-related complications except the thrombosis of a cannula that was left for
      10 days. CONCLUSIONS: The transthoracic Hemopump is an easy-to-use and reliable
      assist device. Left ventricular hypertrophy is a relative contraindication for
      the use of the Hemopump.

PMID- 7646103
TI  - BUN as a risk factor for mortality after coronary artery bypass grafting.
AB  - BACKGROUND: Although information on blood urea nitrogen (BUN) is universally
      available for patients who undergo coronary artery bypass grafting, BUN has not
      often been considered as a risk factor for mortality. This study assessed BUN as
      a risk factor for CABG patients. METHODS: Four data sets were evaluated that
      differed with respect to the types of patients and available patient information.
      In each of these data sets logistic regression analysis was used to examine the
      relationship between BUN and mortality after adjusting for other risk factors.
      RESULTS: Blood urea nitrogen level was strongly associated with mortality in each
      of the data sets. After adjustment for the available risk factors other than
      creatinine level, patients with BUN levels greater than 30 mg/dL had a relative
      odds of mortality ranging between 1.86 and 2.49 (p < 0.0001 in three of the data
      sets). Even after adjustment for creatinine level as well as the other variables,
      BUN was statistically significant at the p less than 0.01 level for three of the
      data sets. CONCLUSIONS: The results suggest that BUN provides additional
      information on cardiac function that supplements the information provided by
      other risk factors.

PMID- 7646104
TI  - Protamine induces endothelium-dependent vasodilatation of the pulmonary artery.
AB  - BACKGROUND: Protamine sulfate, which is used for heparin neutralization, has been
      reported to induce catastrophic pulmonary vasoconstriction after infusion.
      However, in the systemic circulation, protamine infusion induces hypotension due
      to peripheral vasodilation. METHODS: To determine whether protamine also could
      induce vasodilation in the pulmonary circulation, third-order canine pulmonary
      artery segments were studied in vitro in organ chambers. RESULTS: In pulmonary
      artery segments that were caused to contract with phenylephrine (10(-5) mol/L),
      protamine sulfate (40 to 400 micrograms/mL, final organ bath concentration)
      produced concentration-dependent relaxation in canine pulmonary artery segments
      with endothelium (to 74% +/- 7% of the initial contraction to phenylephrine) that
      was significantly greater (p < 0.05) than in segments without endothelium (30% +/
      6% of the initial phenylephrine contraction). Pretreatment of arterial segments
      with NG-monomethyl-L-arginine (10(-5) mol/L), the competitive inhibitor of nitric
      oxide synthesis from L-arginine, did not change tension of arterial segments, but
      NG-monomethyl-L-arginine attenuated the relaxation to protamine. The inhibitory
      effect of NG-monomethyl-L-arginine could be reversed by the addition of L
      arginine (10(-4) mol/L) but not D-arginine (10(-4) mol/L). Endothelium-dependent
      vasodilation to protamine (40 to 400 micrograms/mL) also could be inhibited by
      heparin (8 U/mL, final organ bath concentration). However, the inhibitory effect
      of heparin could be overcome by adding higher concentrations of protamine.
      CONCLUSIONS: Protamine-mediated pulmonary vasodilatation could be an important
      mechanism to protect against the constrictive effects of autocoids generated
      during heparin neutralization. Such a mechanism might be dysfunctional in certain
      persons and put them at risk for pulmonary vasoconstriction after protamine
      infusion.

PMID- 7646106
TI  - Benefits of aortic and pulmonary counterpulsation using dynamic latissimus dorsi
      myoplasty.
AB  - BACKGROUND: Intraaortic and pulmonary artery counterpulsation are useful
      techniques to support circulation during either left or right ventricular
      dysfunction. Electrically stimulated skeletal muscles wrapped around the aorta,
      used as means of cardiac failure treatment, have proved to be an effective method
      of handling experimental left ventricular failure. In this article we report an
      induced cardiac failure model in acute open chest dogs and describe the
      hemodynamic improvement of simultaneous aortic and pulmonary artery
      counterpulsation. METHODS: This was achieved with a bilateral latissimus dorsi
      muscle flap, stimulated with a software written in C++ for Windows. Dynamic
      aortomyoplasty was performed using the left latissimus dorsi muscle flap around
      the descending aorta, and dynamic pulmonaromyoplasty was achieved wrapping the
      pulmonary trunk with the right latissimus dorsi muscle flap. In all animals blood
      pressures and cardiac output were measured after cardiac failure induced by a
      high-dose of propranolol hydrochloride (3 mg/kg intravenously) before and after
      latissimus dorsi muscle flap stimulation. RESULTS: Aortopulmonary
      counterpulsation resulted in a significant increase in mean aortic pressure, mean
      pulmonary pressure, and cardiac output. In addition, a significant decrease was
      observed in end-diastolic left ventricular pressure, systemic vascular
      resistance, and pulmonary vascular resistance. Subendocardial viability index
      (diastolic pressure-time index/systolic tension-time index) in aortomyoplasty and
      tension time index in pulmonaromyoplasty showed significant improvement when
      cardiac assistance was performed by electrical stimulation of both muscles (p =
      0.037 and p = 0.001, respectively). CONCLUSIONS: Treatment of experimentally
      induced cardiac failure using aortopulmonary counterpulsation allows effective
      hemodynamic improvement in open-chest dogs.

PMID- 7646107
TI  - Influence of bypass grafting to the infarct artery on late potentials in coronary
      operations.
AB  - BACKGROUND: Late potentials (LPs) after myocardial infarction identify the risk
      of arrhythmic events and sudden death, and the absence of anterograde flow in the
      infarct-causing occluded coronary artery frequently is associated with LPs on
      signal-averaged electrocardiography. The present study was designed to clarify
      the influence of revascularization of the infarct artery on the LPs in the late
      course after myocardial infarction. METHODS: We studied 21 patients after
      myocardial infarction with positive LPs who had at least one occluded infarct
      coronary artery. We investigated the LPs on signal-averaged electrocardiograms on
      the day of elective coronary artery bypass grafting (CABG) and 1 week after CABG.
      RESULTS: There were 25 infarct arteries in the study patients, 13 of which were
      grafted. The positive LPs disappeared soon after CABG in 13 patients, 10 of whom
      had grafts to all of the infarct arteries. The LPs persisted in 8, who received
      no graft to the infarct artery. One week after CABG, the LPs were still present
      in 4, all of whom had no graft to the infarct right coronary artery. CONCLUSIONS:
      In patients with positive LPs late after myocardial infarction, grafting to the
      infarct artery eliminated the LPs soon after CABG.

PMID- 7646105
TI  - Limiting ischemic myocardial damage using glucose-insulin-potassium solutions.
AB  - BACKGROUND: This experimental study sought to determine whether the infusion of
      glucose-insulin-potassium (GIK) solutions to ischemic myocardium during
      revascularization would decrease myocardial damage. METHODS: In 40 pigs, the
      second and third diagonal vessels were occluded with snares for 90 minutes
      followed by 30 minutes of cardioplegic arrest and 180 minutes of reperfusion.
      During the periods of coronary occlusion and reperfusion, 10 pigs received GIK
      (glucose = 300 g/L, insulin = 50 U/L, K+ = 80 mEq/L) through the jugular vein at
      1 mL.kg-1.h-1 (GIK-IV group); 10 pigs received GIK through the coronary sinus
      (GIK-CS group); 5 pigs received GIK through  the jugular vein during reperfusion
      only (GIK-R group); 5 pigs received GIK through the jugular vein 2 hours prior to
      coronary occlusion and then during the periods of coronary occlusion and
      reperfusion (GIK-Pre group); and 10 pigs received no GIK (Unmodified group).
      Ischemic damage was assessed by wall motion scores using two-dimensional
      echocardiography, changes in myocardial tissue pH, and the area of necrosis in
      the area of risk. RESULTS: Hearts treated with GIK had significantly less tissue
      acidosis, higher wall motion scores, and the least tissue necrosis (14% +/- 2%
      GIK-Pre versus 12% +/- 2% GIK-CS versus 16% +/- 2% GIK-IV versus 25% +/- 2% GIK-R
      versus 73% +/- 4% Unmodified; all, p < 0.05 versus Unmodified). CONCLUSIONS: We
      conclude that a glucose-insulin-potassium solution reduces ischemic myocardial
      damage during coronary revascularization.

PMID- 7646108
TI  - Extended transseptal versus conventional left atriotomy: early postoperative
      study.
AB  - BACKGROUND: Mitral valve operations require excellent exposure. The description
      of an extended vertical transseptal atriotomy by Guiraudon and associates
      promises to provide optimal exposure of the mitral valve. A prospective study was
      carried out to evaluate the merits of the extended vertical transseptal atriotomy
      in comparison with the conventional left atriotomy for mitral valve operations.
      METHODS: Conventional atriotomy was performed in 24 patients (group I) whereas 65
      patients underwent the extended vertical transseptal offroach (group II). They
      were similar in age, sex, cause of disease, New York Heart Association functional
      class, left atrial size, and left ventricular function. The early postoperative
      rhythm changes in these two groups were compared. Statistical studies to analyze
      the significance of incidence of junctional arrhythmia in these two groups were
      carried out. RESULTS: Of the 24 patients in group I, 3 had development of
      transient junctional rhythm after operation, lasting less than 24 hours. None had
      this arrhythmia at the time of discharge. Of the 65 patients in group II,
      junctional rhythm was documented in 25, with a rate of occurrence of 38% (95%
      confidence interval, 27.6% to 52.2%). At the 6-week follow-up, 3 patients still
      had this junctional rhythm, with a failure to recover rate of 12% (3 of 25).
      CONCLUSIONS: The surgical exposure was considered excellent and closure of the
      atriotomy was thought to be easy in group II. However, this should be balanced
      against a significant (38%) incidence of transient junctional rhythm in the early
      postoperative period in group II, probably from injury to sinus node artery or
      atrial conduction pathways.

PMID- 7646109
TI  - Thoracoscopic excision of a posterior mediastinal "dumbbell" tumor using a
      combined approach.
AB  - Up to 10% of neurogenic tumors in the posterior mediastinum demonstrate
      intraspinal extension. Historically, these lesions have been considered
      resectable only by a combined thoracic and neurosurgical approach using
      thoracotomy. Herein, a thoracoscopic excision of a "dumbbell" lesion within the
      framework of a combined approach is described.

PMID- 7646110
TI  - A rare cause of profound cyanosis after Kawashima modification of bidirectional
      cavopulmonary anastomosis.
AB  - The expected level of systemic arterial saturation may not be present after
      bidirectional superior cavopulmonary anastomosis in children with complex
      congenital cardiac anomalies. We present a case of persistent severe cyanosis in
      a patient with azygos continuation of the inferior vena cava after bidirectional
      superior cavopulmonary anastomosis (Kawashima procedure) due to an intrahepatic
      venovenous malformation. Subsequent transcatheter deployment of two Rashkind
      double umbrella devices into the malformation reduced the shunt and markedly
      improved systemic arterial saturation.

PMID- 7646111
TI  - Sternal release and advancement with thoracotomy and osteotomy for idiopathic
      osteopenia.
AB  - Transient neurologic changes developed in a rare case of progressive thoracic
      kyphosis secondary to idiopathic osteopenia with marked spinal and chest cage
      deformities. The patient underwent correction by both anterior thoracic and
      posterior spinal approaches, with concomitant sternal release and advancement.
      After 16 months he continues to have good anatomic and functional results.

PMID- 7646112
TI  - Surgical management of ventricular tachycardia in subannular left ventricular
      aneurysm.
AB  - Submitral left ventricular aneurysms typically affect young adults of African
      ancestry. These aneurysms are characterized by heart failure and mitral
      insufficiency, and occur in the absence of coronary disease. We report a rare
      case of symptomatic ventricular tachycardia in association with submitral left
      ventricular aneurysm (and no mitral insufficiency). Ventricular tachycardia was
      abolished by aneurysm resection and ventricular reconstruction. We suggest
      surgical management is indicated for ventricular tachycardia associated with this
      unusual condition, and may be curative.

PMID- 7646113
TI  - Esophago-airway fistula in AIDS.
AB  - Fistula formation between the esophagus and airway in acquired immunodeficiency
      syndrome is extremely unusual. We report 2 cases, the first in a patient who did
      not undergo definitive surgical management and died shortly after diagnosis. The
      second patient was managed successfully for 5 months by insertion of a Celestin
      endoesophageal prosthesis. This procedure can be performed with low morbidity and
      mortality, and may become the treatment of choice for this complex problem.

PMID- 7646114
TI  - Intravascular ultrasound to assess anastomotic patency after lung
      transplantation.
AB  - Pulmonary arterial anastomotic stenosis is an unusual complication after single
      lung transplantation. Intravascular ultrasound, performed at the bedside with an
      introducer sheath and guidewire, is a new technique that provides high-resolution
      tomographic images of the anastomotic site. This modality was used early in the
      postoperative course of a 58-year-old man to exclude significant pulmonary
      arterial anastomotic narrowing after right single-lung transplantation for
      primary pulmonary hypertension.

PMID- 7646115
TI  - Legionella pericarditis diagnosed by direct fluorescent antibody staining.
AB  - Legionella pericarditis is a rare and serious manifestation of Legionnaire's
      disease. A case is presented in which the diagnosis was established by direct
      fluorescent antibody staining on a pericardial tissue specimen. Video-assisted
      thoracoscopy was used safely and effectively in diagnosis and management in this
      case.

PMID- 7646116
TI  - Colobronchial fistula due to Crohn's disease.
AB  - Enteropulmonary fistulas may present as recurrent localized pneumonia. A case of
      one such fistula originating from the colon in a patient with Crohn's disease is
      discussed.

PMID- 7646117
TI  - Video-assisted thoracic surgical repair of a foramen of Bochdalek hernia.
AB  - A case report of a congenital posterolateral diaphragmatic hernia in an
      adolescent is presented and a technique for thoracoscopic repair of Bochdalek
      hernia is described. Postoperative discomfort was minimal and the hospital stay
      was less than 24 hours. Video-assisted thoracic surgery may be the technique of
      choice for repair of certain congenital diaphragmatic hernias when identified
      after infancy.

PMID- 7646118
TI  - Valved conduit bypass for extensively calcified tricuspid valve stenosis.
AB  - A case of calcified tricuspid valve stenosis resulting from a complication of
      ventriculoatrial shunt implantation is presented. Tricuspid valve repair or
      replacement was not possible because of the prohibitive risk of damaging the
      right atrioventricular junction and conductive pathways. This rare lesion was
      treated successfully by insertion of an external right atrial-right ventricular
      valved conduit. The role of echocardiography in the detection of such a lesion is
      emphasized and the etiologic and therapeutic aspects are discussed.

PMID- 7646120
TI  - Pulmonary arteriovenous malformation complicating coccidioidal pneumonia.
AB  - A patient was treated for lobar pneumonia due to coccidioidomycosis. When the
      pneumonia recurred, the patient was found to have an arteriovenous malformation,
      which had become infected. Complete resolution was achieved with resection and
      postoperative amphotericin B therapy.

PMID- 7646119
TI  - Right latissimus dorsi cardiomyoplasty in diaphragm eventration and cardiac
      malposition.
AB  - Cardiomyoplasty recently has been introduced as a surgical therapy for long
      lasting cardiac dysfunction in selected patients. We report the case of a patient
      affected by chronic heart failure, unresponsive to maximal medical therapy, with
      concomitant posttraumatic injury of the left phrenic nerve, left diaphragm
      eventration, and cardiac malposition (right displacement). In view of the
      progressive deterioration of the cardiac function, cardiomyoplasty was
      recommended, and the right latissimus dorsi muscle was used to perform the
      wrapping procedure. A 6-month follow-up showed significant functional, as well as
      hemodynamic, improvements in addition to a reduction in medical therapy.

PMID- 7646121
TI  - Excision of focal aortic arch atheroma using deep hypothermic circulatory arrest.
AB  - A 68-year-old woman who had a stroke was found by transesophageal
      echocardiography to have two focal areas of pedunculated atherosclerosis in the
      arch of her aorta. Using echocardiographic imaging for guidance in aortic
      cannulation placement and deep hypothermic circulatory arrest, we removed the
      localized atheromata from the otherwise relatively normal aorta. She had an
      uneventful recovery. With the more frequent identification of discrete areas of
      aortic atherosclerosis as a result of transesophageal echocardiography, this
      procedure may become the standard by which to treat this problem.

PMID- 7646122
TI  - Diaphragmatic hernia after right gastroepiploic artery coronary artery bypass
      grafting.
AB  - We report a case of a diaphragmatic hernia, with perforated viscus, originating
      from the diaphragmatic incision that was made to accommodate the right
      gastroepiploic artery coronary artery bypass graft. Avoidance of an excessively
      large right gastroepiploic artery pedicle and interrupted sutures placed at the
      limits of the diaphragmatic incision, perpendicular to the direction of the
      musculotendinous fibers of the diaphragm, should prevent this potentially lethal
      complication. Prompt recognition and treatment of this complication when it
      occurs is lifesaving.

PMID- 7646123
TI  - Orthotopic heart transplantation in situs inversus.
AB  - The case of a successful orthotopic heart transplantation for complete situs
      inversus with double-inlet left ventricle and anomalies of the systemic venous
      return is reported. A piece of aortic homograft and a composite conduit made of
      the recipient right atrium and pericardium were used to connect, respectively,
      the left superior vena cava and the hepatic veins to the right-sided atrium of
      the donor heart.

PMID- 7646124
TI  - Organized thrombus in left main coronary artery in hypoplastic left heart
      syndrome.
AB  - A neonate is reported in whom, during Norwood stage I correction for hypoplastic
      left heart syndrome with mitral stenosis, an organized thrombus was found to
      protrude from the left coronary ostium into the aortic root. With ventricular
      assist device support the patient survived despite severe left ventricular
      ischemia. The presumed origin of the thrombus is from left ventriculocoronary
      arterial connections that serve to decompress the blind left ventricular cavity.

PMID- 7646125
TI  - An alternative to cardioplegia.
AB  - A new method of cardioplegia using an ultrashort beta 1-selective blocker is
      described. The method is especially useful in reoperation in patients with a
      patent internal mammary artery. Four patients have been operated on using this
      method.

PMID- 7646126
TI  - Survival in early-stage non-small cell lung cancer.
AB  - The duration of survival in early-stage lung cancer (stages I and II) varies
      between reports in the literature. Several reasons account for this: patient
      population heterogeneity, inconsistent staging, anatomic variability, dissimilar
      tumor morphology, and unpredictable tumor biology. This report addresses some of
      the issues in early-stage non-small cell lung cancer that relate to variability
      between estimates of survival in end stage reporting. We review several large
      series since the introduction of the International Staging System in 1986 and
      other selected, contemporary reports that address end results in patients with
      pathologic stage I or stage II lung cancer. Overall survival for patients with
      pathologic stage I disease is 64.6% (range, 55% to 72%) and 41.2% for patients
      with stage II disease (range, 29% to 51%). Reducing morphologic differences by
      placing patients in groups based on the TNM subset and refinement in
      categorization by matching TNM subsets based on histology and other factors can
      improve considerably homogeneity and enhance prognostic predictability. The
      development of more accurate measures for predicting prognosis may serve to
      clarify the roles of primary and adjuvant treatment, particularly in those
      patients with early-stage disease associated with poor prognostic factors in whom
      the potential for long-term survival is reduced.

PMID- 7646127
TI  - On the need for improved transfusion indicators in cardiac surgery.
AB  - Guidelines for transfusion practice have had limited impact in altering physician
      transfusion behavior in patients undergoing cardiac operations. This may be due
      to a lack of consensus on the relative risks and benefits of blood in these
      patients who are anemic, limited access to timely data that are necessary on
      which to base transfusion decisions, the recognition that empiric
      hemoglobin/hematocrit thresholds are limited clinical indicators of the need for
      blood, or a combination of these. We present an overview of current transfusion
      and blood conservation practices in this setting, along with possible approaches
      to guide the decision-making process by coupling the use of transfusion
      algorithms with point of care testing to use more physiologic indicators of the
      need for blood transfusion.

PMID- 7646128
TI  - 1988: Pulmonary homograft implantation for ventricular outflow tract
      reconstruction: early phase results. Updated in 1995.

PMID- 7646129
TI  - 1988: Comparison of bioimpedance and thermodilution methods for determining
      cardiac output: experimental and clinical studies. Updated in 1995.

PMID- 7646130
TI  - Clearance after lobectomy and the role of completion pneumonectomy.

PMID- 7646131
TI  - Stent the open sternum after cardiac operations.

PMID- 7646132
TI  - Pneumonectomy for infection.

PMID- 7646133
TI  - Pneumonectomy for infection.

PMID- 7646134
TI  - Bronchopleural fistula after pneumonectomy.

PMID- 7646135
TI  - Importance of early relief of aortic outflow obstruction in univentricular
      hearts.

PMID- 7646136
TI  - Pedicled pericardial fat hemostasis.

PMID- 7646137
TI  - Allograft implantation in pediatric cardiac surgery: surgical experience from
      1982 to 1994.
AB  - Between July 1982 and April 1994, a total of 290 patients (median age 6.5 years,
      range 1 month to 32.1 years, 69 patients younger than 1 year) underwent repair of
      their cardiac malformation by insertion of an allograft. The diagnoses were
      truncus arteriosus communis (n = 78, 27.0%), tetralogy of Fallot (n = 59, 20.0%),
      pulmonary atresia (n = 72, 25.0%), double outlet right ventricle (n = 15, 5.0%),
      complex transposition of the great arteries plus pulmonary stenosis (n = 37,
      13.0%), and others (n = 29, 10.0%). Either pulmonary (n = 69) or aortic (n = 221)
      cadaver allografts were implanted. Two hundred twenty-nine of the allografts were
      antibiotic preserved. Since January 1991 (n = 61), a new cryopreservation
      procedure was employed for standardized uniform cooling using heat sinks and
      defined package geometry. Follow-up was complete for 95.2% (n = 276, 1,320
      patient-years). Thirty-day mortality was 9.0% (n = 26) and late mortality was
      12.1% (n = 35). Kaplan-Meier analysis revealed that patient survival was
      determined mainly by their underlying cardiac disease. All allografts with valve
      sizes less than 15.0 mm had to be exchanged within 7 years as these patients had
      outgrown their conduits. When the allograft was larger than 15.0 mm, exchange was
      necessary in 20% at 10 years. ABO compatibility and aortic or pulmonary origin of
      the allograft were not significant influences on allograft survival.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7646138
TI  - Large-caliber cryopreserved arterial allografts in vascular reconstructive
      operations: early experience.
AB  - Between October 1992 and June 1994, 16 patients (mean age, 55.6 years) underwent
      vascular reconstruction using cryopreserved arterial allografts. Aortoiliac
      aneurysms, vascular infections, and trauma accounted for the majority of case
      diagnoses. Twenty allografts were implanted. Two patients died in the hospital
      (12.5%) and 1 patient died 9 months after the operation. Early patency rate on
      angiography is 92.9%. Follow-up averages 8.2 months. Large-caliber cryopreserved
      arterial vascular allografts seem to provide satisfactory clinical results.

PMID- 7646139
TI  - Structure-function correlations in cryopreserved allograft cardiac valves.
AB  - This communication briefly summarizes a morphologic investigation of explanted
      cryopreserved heart valves and discusses the findings in the context of ongoing
      debates regarding modes of failure, cellular viability, durability of the
      extracellular matrix, and the contribution of immune responses. We studied 20
      cryopreserved human heart valve allografts functioning up to 9 years as either
      orthotopic aortic valves/root replacements or right ventricle-to-pulmonary artery
      conduits explanted for valve failure, infection, or growth-related conduit or
      valve stenosis. Implanted valves had progressively severe loss of normal layered
      structure and were devoid of stainable deep connective tissue cells. Inflammation
      was minimal. Other late findings included minimal inflammation, mild cuspal
      hematomas, mural thrombus, and calcification, most prominent in the aortic wall.
      Transmission electron microscopy of late explants revealed nonviable cells and
      their debris, and a collagenous skeleton that was largely intact. We conclude
      that cryopreserved allograft heart valves have minimal, if any, viable cells, but
      largely retain the original collagen network; preservation of the autolysis
      resistant collagenous skeleton likely provides the structural basis of function.
      Our results also suggest that immune responsiveness has little, if any, impact on
      late allograft function or degradation.

PMID- 7646141
TI  - Viability studies of human valves prepared for use as allografts.
AB  - The preimplantation viability status of pulmonary and aortic valves prepared for
      use as allografts by the methods in current use at Green Lane Hospital, Auckland
      was determined by autoradiography and culture. The valves were obtained from
      cadaver donors, disinfected in antibiotic solution and stored by
      cryopreservation. A group of 45 banked valves considered unsuitable for clinical
      use was assayed initially and very few were found to have viable fibroblasts in
      their leaflets. A series of 29 valves collected at postmortem examination then
      was assayed sequentially after each phase of the preparation procedure. Valves
      obtained within 24 hours of donor death usually retained considerable viability.
      However, in all but a minority of cases this declined markedly after antibiotic
      treatment and further still after cryopreservation, so that most valves were
      nonviable when thawed.

PMID- 7646140
TI  - Effect of warm ischemia and cryopreservation on cell viability of human allograft
      valves.
AB  - Fibroblast viability of the allograft valve leaflet has been suggested to affect
      clinical durability. Warm ischemic time is thought to be one of the critical
      determinants of cell viability. We assessed cell viability of allograft valves by
      flow cytometry, using a fluorescein diacetate-propidium iodide stain to
      characterize the effects of warm ischemia and cryopreservation on viability.
      Twelve human pulmonary valves with harvest-related warm ischemic times (range, 70
      to 520 minutes; mean +/- standard deviation, 225 +/- 157 minutes) were studied by
      flow cytometry. We assessed cell viability of the allograft valve leaflets before
      and 30 days after storage. A significant negative correlation was found between
      warm ischemic time (x minutes) and cell viability (y%) before (y = -0.024x +
      96.7; r2 = 0.62; p = 0.002) and after 30 days of storage (y = -0.036x + 94.0; r2
      = 0.86; p = 0.001). Cell viability of the cryopreserved allograft valves was well
      preserved (> 70%) with a warm ischemic time less than 520 minutes (8.7 hours).

PMID- 7646142
TI  - Immunologic reaction and viability of cryopreserved homografts.
AB  - Homograft cell viability after cryopreservation was investigated and
      cytoimmunologic monitoring was performed during the early postoperative course to
      research possible immunologic reactions after allograft aortic valve replacement.
      After cryopreservation, morphologic observations were made, a nonradioactive cell
      proliferation assay was used, and prostaglandin I2 secretion of the remaining
      endothelial cells was determined. Cytoimmunologic monitoring was performed daily
      within the first 3 weeks postoperatively. An increase of the activation index
      greater than 1 was rated as an immunologic reaction. Maintained metabolic
      activity of graft endothelial cells after cryopreservation was confirmed by
      prostaglandin I2 release (9.24 +/- 3.48 ng/cm2 basic release and 20.1 +/- 5.76
      ng/cm2 when stimulated with 25 mumol/L Na arachidonic acid). Cell proliferation
      was indicated after graft incubation with the nonradioactive viability kit (0.27
      +/- 0.9 at 450 nm). Cytoimmunologic examinations (n = 861) after homograft
      implantation showed a more intense activation in patients with ABO-incompatible
      grafts (activation index 2.1 +/- 1.6, n = 16) than in those with ABO-compatible
      grafts (activation index 1.3 +/- 0.8, n = 17). In these groups, the duration of
      activation by cytoimmunologic monitoring was 2.8 +/- 1.5 days and 1.3 +/- 0.6
      days, respectively (p < 0.041). No activation was observed in 8 patients after
      xenograft valve replacement (p < 0.01). Our data indicate that cryopreservation
      of homograft valves represents a cell- and tissue-protective preservation method.
      Postoperatively, all homograft valves caused immunologic reactions, which were
      reversible without immunosuppression treatment.

PMID- 7646143
TI  - Humoral immune response to human aortic valve homografts.
AB  - The humoral response to homograft valves in humans is largely unknown. The anti
      human lymphocyte antigen (HLA) antibody production, specificity, and
      immunoglobulin class were examined sequentially in 73 patients undergoing aortic
      valve replacement. In addition, the long-term production of antibodies was
      examined in a cross-sectional study of 160 patients at periods varying from 1 to
      15 years postoperatively. Human lymphocyte antigen antibodies were produced in 17
      of 30 antibiotic-sterilized homografts (56%) and in 15 of 15 "homovital"
      homograft recipients, compared with 6 of the 28 control xenograft recipients
      (21%) (p < 0.001). The HLA antibodies were immunoglobulin G in all 15 homovital
      homografts, in 11 of 17 antibiotic-sterilized homografts, and in four of the six
      xenograft cases. Human lymphocyte antigen specificities could be assigned to the
      antibodies in 21 cases. In 10 of 11 cases in which donor HLA typing data were
      available, the antibodies detected were directed against donor HLA class I
      antigens. Of six possible determinants of HLA antibody production, the type of
      homograft valve implanted (homovital or antibiotic sterilized) correlated with
      antibody formation. In the cross-sectional study, 66 of the 85 homovital
      homograft recipients tested for HLA antibodies after 1 year were found to have
      antibodies, compared with 29 of 75 antibiotic-sterilized homograft recipients (p
      = 0.00003). We conclude that homografts appear to stimulate a strong donor HLA
      specific antibody response, particularly of the immunoglobulin G class. This is
      most common in homovital valve recipients. These antibodies can persist for 15
      years after operation. The clinical significance of this response requires
      further investigation.

PMID- 7646144
TI  - Stimulation of immune-competent cells in vitro by human cardiac valve-derived
      endothelial cells.
AB  - Both fresh and cryopreserved human cardiac valve allografts are transplanted
      without matching donor and recipient for blood group or human leukocyte antigens
      (HLA) and without the usual immunosuppressive therapy that follows organ
      transplantation. Calcification occurs in almost all transplanted valves, and in
      children acute valve failure is frequently seen. We hypothesized that failure of
      the human valve allografts could have an immunologic basis. This hypothesis was
      tested in a functional way by performing lymphocyte stimulation assays using
      fresh and cryopreserved valve pieces and endothelial cells derived from valve
      leaflets as stimulator. Human peripheral blood lymphocytes, both matched and
      mismatched for HLA antigens, were used as responder cells. The results were
      expressed as the stimulation index. Fresh valve pieces induced a significantly
      higher stimulation index (median, 9; range, 4 to 117) compared with the
      cryopreserved pieces (median, 2; range, 0 to 9; p = 0.002 by Wilcoxon test). The
      stimulation index was significantly reduced when lymphocytes matched for HLA-DR
      with the valve pieces were used (median, 1; range, 0 to 5) as compared with the
      HLA-DR-mismatched combination (median, 4; range, 2 to 117; p = 0.006, Wilcoxon
      test). Valve leaflet-derived endothelial cells were able to induce a median
      stimulation index of 8 (range, 3 to 15) when incubated with lymphocytes
      mismatched for HLA-A, -B, and -DR. In conclusion, stimulation of immune-competent
      cells in vitro is induced by both fresh and cryopreserved human valve pieces and
      by endothelial cells derived from fresh valve leaflets. The immune response can
      be reduced by using cryopreserved valves or by matching valve donor and responder
      lymphocytes for HLA-DR.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7646145
TI  - The aortic valve after heart transplantation.
AB  - We studied the aortic root (wall, semilunar cusp, septal myocardium) in 37
      patients (29 male and 8 female; mean age; 41 years) who died 2 to 4,380 days
      (mean, 398 days) after heart (n = 34) and heart-lung (n = 3) transplantation. The
      aim of the study was to assess tissue viability, graft-host biological
      interaction, and cusp mineralization with time. Study methods included gross
      inspection and photos of each specimen, microradiography, histology and
      immunohistochemistry, scanning and transmission electron microscopy, and atomic
      absorption spectroscopy. There were no cases of valve dysfunction; in particular,
      cusp tears or perforations never occurred. Only 1 valve, in place for 12 years,
      had a pin-point calcification visible to the naked eye. Optimal preservation of
      the tissue components (endothelium, fibroblasts, collagen and elastic fibers,
      proteoglycans, intrinsic nervous ganglia) was observed at both short and long
      term. Concomitant acute rejection of valve leaflets and myocardium was seen in 7,
      mild valve thickening in 14, myxoid degeneration in 4, and graft aortic
      atherosclerosis in 26. Mineralization was negligible and was not progressive with
      time. No linear correlation was found between mineralization and number of acute
      rejections. In conclusion, we observed optimal cusp viability and integrity even
      at long term, concomitant valve and myocardium rejection with no valvular
      sequelae, and negligible, non-progressive cusp calcification. Donor-recipient
      blood group matching, heart-beating donor, and chronic immunosuppression are the
      reasonable explanations of the optimal durability of the aortic valve after heart
      transplantation.

PMID- 7646146
TI  - Histologic and genetic assessment of explanted allograft valves.
AB  - A possible way of analyzing the immune response triggered by the allograft and
      the cellular viability is to compare immunocompetent and immunosuppressed
      patients, such as those having valve replacement and heart transplantation,
      respectively. These groups differ in immunosuppression therapy, preparation
      methods, valve hemodynamics. In the present study, we investigated polymerase
      chain reaction-amplified DNA flanking hypervariable (CA)n regions obtained from
      valve leaflets taken from patients having valve replacement or heart
      transplantation and performed a histologic analyses of the cells. In addition, we
      assessed an autograft valve to compare the hemodynamic effects on the cellular
      composition of the valve leaflet. We conclude that leaflet cellularity of the
      heart transplantation and autograft patients is superior to that of the valve
      replacement patients. These differences were consistent with the occurrence of an
      immune response in the valve replacement group, which was prevented or abrogated
      by immunosuppressive therapy administered to the heart transplantation group.
      However, it cannot be excluded that preparation procedures have a long-term
      effect on the extracellular matrix, leading to deterioration of cell adhesion and
      homing conditions.

PMID- 7646148
TI  - Unexplained fever after aortic valve replacement with cryopreserved allografts.
AB  - The incidence of fever of unknown origin was studied in 3 groups of patients
      undergoing aortic valve replacement. Fever of unknown origin was defined as a
      fever greater than 38.3 degrees C detected after the third postoperative day and
      which initiated a negative "fever work-up." Fifty patients underwent aortic valve
      replacement using cyropreserved allografts. Of the 49 patients who survived the
      operation, 13 (26%) developed fever of unknown origin. Only 1 (2%) of 51
      patients, and 4 (8%) patients undergoing aortic valve replacement with a
      mechanical prosthesis and porcine xenograft, respectively, developed fever of
      unknown origin (p = 0.0034). Fever of unknown origin after allograft aortic valve
      replacement developed between the fourth and sixth postoperative days, with no
      other associated symptoms or signs. It lasted for 24 to 48 hours, and resolved
      without treatment. Univariate analysis revealed that fever of unknown origin
      occurred in younger patients (39.9 +/- 9.4 versus 50.8 +/- 11.8 years of age).
      The mean white blood cell count in fever of unknown origin and afebrile patients
      were similar (10.4 +/- 3.2 and 8.9 +/- 2.3, p = NS), both of which were
      significantly lower than the white blood cell count in patients with documented
      infection (15.0 +/- 5.2, p = 0.02; p < 0.001). No association could be
      demonstrated between the fever of unknown origin and gender, previous
      endocarditis, operative technique, cardiopulmonary bypass or cross-clamp times,
      ABO match, or perioperative blood transfusions. We conclude that a significant
      number of patients undergoing allograft aortic valve replacement develop
      noninfectious postoperative fever. The etiology remains unknown, but low-grade
      rejection cannot be excluded.

PMID- 7646149
TI  - Age-dependent changes in the radial stretch of human aortic valve leaflets
      determined by biaxial testing.
AB  - The maximum radial elastic extensibility (stretch) of human aortic valve leaflets
      was measured as a function of the donor age using biaxial testing techniques. The
      36 leaflets tested were removed from 18 unimplanted cryopreserved aortic
      allograft valves retrieved from donors aged 15 to 58 years. The stretch was
      measured at a traction of 60 Nm-1 and analyzed as a function of the age of the
      donor. It was found that at 15 years, the radial stretch is about 80% but
      declines rapidly (linearized rate of 4% per year) to be 40% by the age of 25
      years. The stretch stays approximately constant until the age of 40 years and
      then undergoes a steady decline at the rate of about 1% per year at least until
      the age of 58 years. These results demonstrate that stretch, which is important
      for the maintenance of adequate coaptation area, is not permanent but may be lost
      at a relatively rapid rate for reasons that are not yet understood. Stretch loss
      in the leaflets also must be a contributing factor to the development of aortic
      incompetence. The probability of postoperative stretch loss needs to be allowed
      for in sizing protocols for aortic allografts.

PMID- 7646147
TI  - Short-course cyclosporin A therapy for definite allograft valve survival
      immunosuppression in allograft valve operations.
AB  - This study was designed to determine the effect of short-course cyclosporin A
      therapy (10 mg/kg daily for 14 days) on allograft valve survival across the
      histocompatibility barriers in the following rat models; (1) syngeneic Lewis to
      Lewis (herein referred to as autografts), (2) weakly allogeneic AS to Lewis (RT1
      compatible, non-RT1-incompatible), and (3) strongly allogeneic CAP to Lewis (RT1
      and non-RT1-incompatible). Cyclosporin A-treated and untreated recipient animals
      (Lewis) received allovital and antibiotic-treated viable allografts implanted
      into the infrarenal aorta. Second-set skin grafting was performed 3 weeks after
      heterotopic valve implantation to test for immunogenicity and presensitization.
      The animals (Lewis) were sacrificed serially on days 20, 50, 100, and 150 for
      immunofluorescence study using mouse monoclonal antibodies (OX6) directed at
      class II endothelial surface antigens. The allografts in weakly allogenic strains
      showed no humoral response under a short course of cyclosporin A. The cyclosporin
      A-untreated allovital grafts and the viable (antibiotic-treated) valves
      demonstrated fibrocalcification on the 100th and 150th postoperative days,
      respectively. In conclusion, it seems that a short course of nontoxic
      immunosuppression could arrest allograft rejection and thus prevent early
      degeneration of allografts. Furthermore, antibiotic-treated viable allografts
      seemed to be more durable than allovital grafts.

PMID- 7646150
TI  - Biaxial mechanical properties of explanted aortic allograft leaflets.
AB  - The leaflets of 33 aortic allograft valves inserted using the freehand method
      were retrieved at reoperation, and the mechanical properties of the tissue were
      measured using biaxial testing methodology. Before insertion, the valves had been
      sterilized for 24 hours in either PSKA or CLPVA antibiotic solutions and then
      were either wet stored or cryopreserved. The cryopreserved valves were sterilized
      with CLPVA only, so there were three different treatment types in all. The
      controls were a set of unimplanted cryopreserved aortic valves. The radial
      stretch of the valve leaflets was measured and was analyzed as a function of the
      age of the donor in the case of the controls and the age of the donor plus the
      duration of implantation for the explanted valves. The biaxial tension test was
      used to determine the maximum radial stretch of each leaflet because this
      variable dictates the area of coaptation and, ultimately, valve competency. It
      was found that the radial stretch of the allograft leaflets after implantation
      declined faster with time than did the stretch of the native aortic valve leaflet
      controls. This greater rate of stretch reduction depended mostly on the degree of
      similarity between the stretch of the donor leaflets and that of the recipient at
      the time of implantation. No conclusion could be reached about the influence of
      the preimplantation storage method because of the different time intervals of
      implantation applicable to each case. After matching for annulus size, matching
      the ages of donor and recipient is a good graft-selection strategy, but it may be
      better to use a slightly older donor.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7646151
TI  - Cracks in cryopreserved aortic allografts and rapid thawing.
AB  - Cryopreserved aortic allografts are shipped in a frozen state. Cracks in the
      graft, appearing after thawing, can pose serious problems in the planned
      operative procedures. Cracks were encountered in approximately 3% of all our
      shipped cryopreserved human material and were strongly associated with
      transportation in a "dry shipper." We practice two other modes of transport: on
      dry ice and directly to our operating room. We studied the temperature behavior
      during thawing of 17 porcine aortic valves in three groups. The valves were
      frozen and stored like our human valves. Before thawing, they were subjected to
      stimulated transport in either a dry shipper, on dry ice, or to the operating
      room. Differences between the groups were noted in the maximal rate of thawing of
      the inner as well as the outer wall. The highest maximal thawing rates were
      observed in the dry shipper group, in which 66% of the valves cracked. We
      therefore suspended transportation of cryopreserved human valves by means of a
      dry shipper.

PMID- 7646152
TI  - Histologic modification by cryopreservation in rat aortic allografts.
AB  - Histologic changes after the cryopreserved rat aortic transplantation were
      studied, and the influences of the cryopreservation and of the allografting on
      the histology were examined. Four groups of Brown Norway (RT1n) and Lewis rats
      (RT1(1)) were used (n = 4 at each examined period in each group): the
      cryopreservation-allograft group (from Brown Norway to Lewis with
      cryopreservation), the cryopreservation-isograft group (from Lewis to Lewis with
      cryopreservation), the fresh allograft group (from Brown Norway to Lewis without
      cryopreservation), and the fresh isograft group (from Lewis to Lewis without
      cryopreservation). The graft was harvested from a descending thoracic aorta of a
      donor rat, implanted to an infrarenal abdominal aorta of a recipient rat, and
      extracted at 10 days, 1, 3, 6, and 12 months after the operation. The intimal
      thickening, cellular loss in the media, and cellular infiltration in the
      adventitia were observed, which were the same phenomena seen in chronic rejection
      of human organ allografts. Although the degree of intimal thickening and cellular
      loss in the media were higher in the cryopreserved groups than in the fresh
      groups, the cryopreservation procedure suppressed cellular infiltration in the
      adventitia after allotransplantation. The immunologic attack against the graft
      might be diminished by cryopreservation.

PMID- 7646153
TI  - Pulmonary autograft for aortic valve replacement in rheumatic disease: a caveat.
AB  - Pulmonary autograft replacement of the aortic valve offers an attractive option
      in the younger patient with growth potential and long-term survival. In our
      institution between January 1990 and August 1994, 78 patients have undergone this
      procedure. The mean age was 18.6 +/- 7.36 years (range, 1 to 41 years). The
      etiology was rheumatic in 63 patients (80.7%). Aortic regurgitation was the
      predominant lesion in 60 patients (76.9%). Significant mitral regurgitation
      requiring operation was present in 22 patients (28.2%). All patients underwent
      pulmonary autograft replacement of the diseased aortic valve and the mitral valve
      was repaired in 22 patients. There were no hospital mortality, endocarditis, or
      thromboembolism in the series up to date. There have been two late non-cardiac
      deaths. Five patients (6.4%) required reoperation, one for mitral repair failure
      and four for autograft failure. Acute rheumatic valvulitis was demonstrated in
      one of the reoperated patients. Echocardiography of 68 patients followed up more
      than 2 months show progression of aortic regurgitation more than 2/4+ in 12
      patients (15.4%). Four of these patients have been reoperated without mortality.
      In conclusion, although the Ross procedure remains a safe and attractive
      alternative in aortic valve operation, the progression of aortic regurgitation,
      especially in the younger patient with rheumatic etiology, remains a concern.

PMID- 7646155
TI  - Extended aortic root replacement with pulmonary autografts: experience in 14
      cases.
AB  - The surgical relief of complex multilevel left ventricular outflow tract
      obstruction remains a challenging problem. We present a new operation that
      combines the concepts of aortoventriculoplasty, extended aortic root replacement,
      and the use of a pulmonary autograft. Fourteen patients underwent this operation:
      9 patients after previous attempts to relieve diffuse subvalvular stenosis and 5
      patients who had excessive gradients over an outgrown aortic valve prosthesis.
      All patients except 1 survived the operation. Complete heart block developed in 1
      patient after a septal infarction. One patient remained in congestive heart
      failure and died suddenly after 17 months. All other patients are in New York
      Heart Association class I after a mean follow-up of 20 +/- 12 months. All
      patients showed excellent function of the autograft and homograft valve at follow
      up. This operation might present a more durable or even a definitive solution in
      the management of these complex left ventricular outflow tract obstructions.

PMID- 7646154
TI  - Aortic valve replacement with pulmonary autograft in children and adults.
AB  - Aortic valve replacement with a conventional prosthesis is still flawed with
      complications, especially in children and young adults. Complex aortic root
      enlargement (Konno) is often needed because of small aortic diameter. The poor
      compliance with anticoagulation by teenagers and the risks associated with this
      made us look at alternative techniques. From November 1990 to June 1994, 70
      patients were considered for pulmonary autografts in our institution; 64
      underwent the procedure with one death and one failure to implant. Short-term
      results are excellent, with minimal gradient in 90% and minimal regurgitation in
      96% of the patients. The long-term follow-up, hopefully, will confirm the
      superiority of this procedure over more conventional replacement.

PMID- 7646156
TI  - Aortic valve replacement with cryopreserved pulmonary allografts: five years'
      follow-up.
AB  - Excellent clinical results with pulmonary autografts and experimental evidence
      that pulmonary valves can withstand the higher stress in the systemic circulation
      led us to use the cryopreserved pulmonary allograft for aortic valve replacement.
      From September 1988 until March 1993, 126 consecutive patients (61 +/- 10 years;
      74 men and 52 women) underwent aortic valve replacement with a cryopreserved
      pulmonary allograft. All allografts were inserted freehand in the subcoronary
      position. There were four in-hospital deaths (3.2%), and 1 patient had severe
      valvular incompetence immediately postoperatively, requiring reoperation after 4
      weeks. One hundred twenty-one patients were followed up in 3- to 6-month
      intervals for 25.3 +/- 16.3 months (range, 6 to 66 months), and valve performance
      was assessed routinely by means of color-flow Doppler echocardiography. Nine
      patients (7.1%) died during follow-up. Two patients died of multiple septic
      emboli during bacterial endocarditis, and 1 patient died of a massive stroke. The
      other 6 patients died of myocardial infarction (4), respiratory insufficiency due
      to chronic obstructive lung disease (1), and carcinoma (1). Ninety-four patients
      (78%) had absent or trivial aortic valve regurgitation. Valvular incompetence
      class II was present in 3 patients (2.5%), whereas 5 others (4%) demonstrated
      class II to III. Severe aortic regurgitation (class III or IV) could be detected
      in 10 patients (8.3%). All underwent reoperation and replacement of the valve
      with a prosthetic device. Bacterial endocarditis caused graft incompetence in 3
      patients, valve degeneration was detected in another 3, and technical mistakes at
      valve implantation caused valve failure in the other 4.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7646157
TI  - The autologous tissue cardiac valve: a new paradigm for heart valve replacement.
AB  - This is a report of early clinical experience with an autologous tissue cardiac
      valve, which demonstrates the feasibility of making a bioprosthesis in the
      operating room in 10 minutes at the time of the valve replacement operation.
      There were 30 implant patients (18 men, 12 women), with ages ranging from 32 to
      83 years. Diagnoses included calcified aortic stenosis (n = 16), pure aortic
      insufficiency (n = 9), and mixed aortic stenosis and insufficiency (n = 5).
      Associated diagnoses have included chronic renal failure treated with dialysis (n
      = 1), coronary artery disease requiring concomitant coronary bypass (n = 1),
      ascending aortic aneurysm requiring resection (n = 3), and mitral insufficiency
      requiring concomitant mitral valvuloplasty (n = 2). All of the valve replacements
      were in the aortic position. These implanted patients are being followed up
      carefully according to the protocol that requires examination every 6 months for
      the first year and every 12 months subsequently. No patient has been lost to
      follow-up. Twenty-seven patients are alive and well from 1 to 22 months
      postoperatively. There were three deaths: two perioperative deaths (one
      perivalvular leak and one hemorrhage) and one infective endocarditis 1.3 years
      after valve replacement. All surviving patients were followed up by
      echocardiographic examination (mean gradient, 15.5 +/- 6.8 mm Hg at 1 year). In
      conclusion, the feasibility of this method and concept has been demonstrated with
      implants in 30 patients. The validity of the technique will be judged by clinical
      results and experiences in children.

PMID- 7646158
TI  - Mechanical properties of porcine pulmonary valve leaflets: how do they differ
      from aortic leaflets?
AB  - This study measured the biaxial properties of pulmonary and aortic leaflets in
      extension in the fresh state and then in the same samples after fixation with
      glutaraldehyde. The results showed that when fresh, the valves had a similar
      response to load in the circumferential direction, but the pulmonary leaflets
      were more extensible in the radial direction. They were also less stiff. Fixation
      decreased the tissue extensibility and increased the stiffness of the pulmonary
      leaflets much less than in the aortic leaflets. This was interpreted to mean that
      the collagen content of the pulmonary leaflets is significantly less than that in
      the aortic leaflets. Reduced collagen content would be expected to enhance
      hemodynamic performance because of increased leaflet stretch and reduced
      stiffness. However, lower collagen levels may reduce implant durability.

PMID- 7646161
TI  - Biological valves beyond fifteen years: the Wessex experience.
AB  - Between 1975 and 1979, 443 biological valves (298 Carpentier-Edwards, 134
      homograft, and 11 Hancock valves) were implanted in 415 patients (age, 16 to 77
      years; mean, 59 years) with an operative mortality of 2.9%. Total follow-up was
      4,248 patient-years. Overall event-free survival was 60% +/- 1.5% (standard
      deviation) at 10 years and 29% +/- 1.4% at 15 years. Ten-year and 15-year event
      free survival were 72% +/- 3.4% and 41% +/- 3.3% for aortic homografts, 62% +/-
      3% and 33% +/- 2.8% for isolated aortic xenografts, and 43% +/- 3.5% and 14% +/-
      3.0% for isolated mitral xenografts. Freedom from structural valve degeneration
      was 87% +/- 1.3% and 63% +/- 2.5% for all patients at 10 and 15 years,
      respectively, 86% +/- 2.7% and 58% +/- 4.1% for aortic homografts, 93% +/- 1.8%
      and 76% +/- 5.1% for aortic xenografts, and 75% +/- 4.0% and 47% +/- 7.4% for
      mitral xenografts. Of the 110 remaining patients, echocardiography was performed
      in 61 patients (23 aortic xenograft, 24 aortic homograft, 9 mitral xenograft, and
      5 tricuspid xenograft) between 14 and 17 years after implantation. An early
      diastolic murmur was heard in 57% of all aortic valve replacements (AVRs) 62.5%
      of homograft AVRs, and 52% of xenograft AVRs. Echocardiographically, aortic
      regurgitation was detected in 79%, 83%, and 74% of all AVRs, homografts, and
      xenografts, respectively. Aortic stenosis was present clinically in 11% of all
      AVRs, 4% of homograft AVRs, and 17% of xenograft AVRs.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7646160
TI  - Comparison of low-pressure versus standard-pressure fixation Carpentier-Edwards
      bioprosthesis.
AB  - Intermediate-phase clinical results of 51 low-pressure (LP) and 234 standard
      pressure (SP) fixation porcine Carpentier-Edwards (CE) valves implanted between
      1977 and 1991 were compared for valve-related events. Group similarities included
      New York Heart Association functional class, ejection fraction, and sex. Patients
      with SP valves were younger (mean age, 58 versus 68 years; p = 0.0001). There
      were 20 in-hospital deaths (8.6%) in the SP valve group and 5 (9.8%) in the LP
      valve group (p = 0.79). Follow-up was 99%, with a mean of 104 months in the SP
      valve group versus 55 months in the SP valve group (p = 0.0001). The actuarial
      survival rate was 48.2% and 22.3% at 10 and 15 years, respectively, in the SP
      valve group and 34.1% at 10 years in the LP valve group (p = 0.42). Freedom from
      events at 5, 10, and 15 years in the SP valve group and at 5 years in the LP
      valve group was as follows: for late valve-related events, 86.3%, 51.4% and
      20.2%, respectively, in the SP valve group versus 85% in the LP valve group (p =
      0.44); for valve-related death, 96.4%, 93.6%, and 87.3% in the SP valve group
      versus 100% in the LP valve group (p = 0.20); for structural valve failure, 96%,
      68%, and 35% in the SP valve group versus 100% in the LP valve group (p = 0.09);
      and for reoperation, 95%, 61%, and 30% in the SP valve group versus 92% in the LP
      valve group (p = 0.82). In conclusion, this study revealed no significant
      statistical difference between LP and SP valves. In the LP valve group,
      structural valve failure/valve-related death was not observed, perhaps indicating
      a more favorable result. Absolute verification of this trend awaits long-term
      follow-up.

PMID- 7646159
TI  - Autologous glutaraldehyde-treated pericardial valved conduit: an experimental
      study.
AB  - Extracardiac conduits in the form of allografts and synthetic tubes containing
      heterograft valves have been used widely in the management of ventricular outflow
      abnormalities and for establishing ventriculoarterial continuity. These
      procedures are limited by long-term calcification as well as by formation of
      neointimal peel, necessitating reoperation. In an effort to continue the search
      for an alternative conduit, we designed and evaluated a valved sinus-bearing
      conduit fashioned out of autologous pericardium treated with glutaraldehyde. The
      construction of the conduit is described. The results of implantation of these
      conduits in 12 sheep showed no progression of gradients, fresh regurgitation, or
      evidence of wall or cusp calcification 9 months after implantation.

PMID- 7646162
TI  - Porcine valve durability: a comparison between Hancock standard and Hancock II
      bioprostheses.
AB  - Two series of patients who received a Hancock standard (HS) (1970 to 1983) and a
      Hancock II (HII) (1983 to 1992) porcine bioprosthesis were reviewed to compare
      bioprosthetic durability. Patients with HS porcine bioprostheses (n = 769)
      differed from those with HII bioprostheses mostly in mean age at operation (47 +/
      12 versus 62 +/- 9 years; p < 0.001); the latter prosthesis was implanted mostly
      in patients older than 50 years. At 8 years after operation, actuarial survival
      was 57% +/- 4% after aortic, 61% +/- 3% after mitral, and 39% +/- 7% after mitral
      aortic valve replacement with the HS bioprosthesis; actuarial survival was 51% +/
      9%  after aortic, 66% +/- 6% after mitral, and 49% +/- 10% after mitral and
      aortic valve replacement with an HII bioprosthesis. No cases of structural
      deterioration of HII bioprostheses were observed at 8 years in any patients.
      Actuarial freedom from structural valve deterioration was 78% +/- 4% after
      aortic, 88% +/- 3% after mitral, and 79% +/- 7% after mitral-aortic valve
      replacement with an HS bioprosthesis at 8 years. In all patients greater than 50
      years of age, actuarial freedom from structural valve deterioration at 8 years
      was 90% +/- 3% in patients with an HS bioprosthesis and 100% in those with an HII
      bioprosthesis (p = 0.08). A trend to an improved durability of the HII
      bioprosthesis compared with the HS was observed during the first 8 postoperative
      years. Because these results could be influenced partly by the age difference in
      the two series of patients, a longer follow-up is needed to confirm these data.

PMID- 7646164
TI  - The Hancock II bioprosthesis at ten years.
AB  - The Hancock II bioprosthesis was used for heart valve replacement in 843 patients
      from 1982 to 1993. Aortic valve replacement (AVR) was performed in 536 patients,
      mitral valve replacement (MVR) in 250, and aortic and mitral valve replacement
      (DVR) in 57. The mean age was 64 +/- 12 years. Before operation, 80% of the
      patients were in New York Heart Association functional class III or IV;
      approximately one-third of the patients had coronary artery disease, and 60
      patients had ascending aorta aneurysm. There were 47 operative deaths (AVR, 4%;
      MVR, 7%; DVR, 10%) and 147 late deaths. Follow-up was complete in 98.6% of the
      patients and extended from 3 to 140 months (mean, 59 months). At the last follow
      up, 84% of the patients were in New York Heart Association class I or II. The
      actuarial survival at 10 years was 63% +/- 4% for AVR, 55% +/- 5% for MVR, and
      53% +/- 9% for DVR. At the end of 10 years, the freedom from thromboembolic
      complications was 80% +/- 4% for AVR, 88% +/- 3% for MVR, and 86% +/- 5% for DVR;
      the freedom from endocarditis was 95% +/- 2% for AVR, 96% +/- 1% for MVR, and 87%
      +/- 5% for DVR; the freedom from primary tissue failure was 92% +/- 3% for AVR,
      81% +/- 6% for MVR, and 65% +/- 16% for DVR; and the freedom from reoperation was
      89% +/- 2% for AVR, 81% +/- 6% for MVR, and 61% +/- 15% for DVR. The durability
      of this bioprosthetic valve was affected by the patient's age and by the position
      where it was implanted. The clinical results of the Hancock II bioprosthesis at
      10 years are comparable to those of other current porcine and pericardial valves.

PMID- 7646163
TI  - Durability of the Hancock MO bioprosthesis compared with standard aortic valve
      bioprostheses.
AB  - To compare the durability of the Hancock modified orifice (Hancock MO, model 250
      [H-MO]) valve with two other commonly used standard aortic valve bioprostheses, a
      cohort of 1,602 patients undergoing aortic valve replacement using porcine valves
      between 1971 and 1990 (excluding simultaneous mitral valve replacement) was
      analyzed retrospectively using Cox model multivariate techniques. Five hundred
      sixty-one patients received a composite H-MO valve, 652 received a standard
      Hancock model 242 (H) valve, and 389 received a Carpentier-Edwards model 2625 (C
      E) valve. Mean age was 60 +/- 15 years (+/- 1 standard deviation) (71% male).
      Follow-up (10,247 patient-years) extended to 15 years and was 97% complete. The
      main focus of this study was bioprosthetic durability, using The American
      Association for Thoracic Surgery/The Society of Thoracic Surgeons guidelines to
      define structural valve deterioration (SVD). Multivariate analysis revealed that
      (younger) age (p < 10(-5), liver disease (p = 0.02), and 1981 to 1985 operative
      period (p = 0.012) were the only significant, independent predictors of SVD. In
      concordance with previous reports, the SVD freedom estimate was greater than 90%
      at 15 years for patients older than 70 years of age. Hepatic dysfunction had an
      adverse effect on SVD (estimated freedom from event at 10 years was 34 +/- 17%
      [standard error of mean] versus 78 +/- 2% for those without liver disease), but
      this affected only 3% of patients. Interestingly, one operative period (1981 to
      1985) was associated with a slightly higher risk of SVD compared to the three
      other 5-year time windows. Valve type did not emerge as a significant risk factor
      for SVD.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7646165
TI  - Carpentier-Edwards supraannular porcine bioprosthesis: clinical performance to
      twelve years.
AB  - The Carpentier-Edwards supraannular porcine bioprosthesis, a second-generation
      biologic prosthesis, has had clinical performance assessment to 12 years. This
      bioprosthesis was used in 2,489 operations in 2,444 patients between 1982 and
      1992, inclusive (mean age 64.1 years, age range 6 to 89 years). There were 1,335
      aortic valve replacements (AVR), 938 mitral valve replacements (MVR), and 200
      multiple valve replacements (MR). Concomitant procedures were performed in 1,017
      cases (40.9%). The age group distribution was: 35 years or younger, 83 patients;
      36 to 50 years, 245; 51 to 64 years, 728; 65 to 69 years, 458; and 70 years and
      older, 975. The total follow-up was 12,785 patient-years (mean, 5.1 years) and
      was 96% complete. The early mortality rate was 7.4% (185 patients), and the late
      mortality was 4.9%/patient year (623). Concomitant procedures influenced both
      early and late mortality (p < 0.05). The overall patient survival at 12 years was
      44% +/- 3% (p < 0.05, AVR > MVR, MR). The freedom from thromboembolism was not
      different by valve position. The freedom from major thromboembolism at 12 years
      was 82% +/- 4% (p = not significant by valve position). The overall freedom from
      antithromboembolic hemorrhage was 96% +/- 1% at 12 years (p < 0.05, AVR > MVR >
      MR). The overall freedom from valve-related reoperation at 12 years was 58% +/-
      5% (p < 0.05, AVR > MVR, MR), and from valve-related mortality 89% +/- 2% (p <
      0.05, AVR > MVR > MR). The freedom from residual morbidity (permanent impairment)
      at 12 years was 87% +/- 4% (p = not significant by valve position).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7646166
TI  - Structural deterioration in Carpentier-Edwards standard and supraannular porcine
      bioprostheses.
AB  - The Carpentier-Edwards standard (CE-S) porcine bioprosthesis was implanted in
      1214 operations (1975 to 1985) and the Carpentier-Edwards supraannular (CE-SAV)
      bioprosthesis was implanted in 2,489 operations (1982 to 1992 inclusive). The
      early mortality was 7.6% and 7.4% for the CE-S and CE-SAV groups, respectively;
      the late mortality was 5.3% per patient-year and 4.9% per patient-year,
      respectively. The cumulative follow-up was 9,968 patient-years for the CE-S group
      and 12,784 patient-years for the CE-SAV group. Concomitant procedures were
      performed in 26.8% of the patients who received a CE-S and in 40.9% of those who
      received a CE-SAV (p < 0.05). The mean age of the patients receiving a CE-S was
      57.3 years (range, 8 to 85 years) and was 64.1 years (range, 6 to 89 years) in
      those receiving a CE-SAV. The CE-S group consisted of 578 atrial valve
      replacements (AVRs), 512 mitral valve replacements (MVRs), and 115 multiple valve
      replacements (MRs). The CE-SAV group consisted of 1,335 AVRs, 938 MVRs, and 200
      MRs. There was a total of 165 cases of structural valve deterioration (SDV) in
      the CE-SAV group (AVR, 35; MVR, 98; and MR, 32). The effect of trimming the
      aortic wall was also considered: 20 of the 931 trimmed prostheses used for MVRs
      and MRs and none of the 207 reduced-trimmed prostheses exhibited SVD. The
      cumulative follow-up was 5,422 years for the patients with trimmed prostheses and
      470 for those with reduced-trimmed prostheses.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7646167
TI  - Durability of the Carpentier-Edwards porcine bioprosthesis: role of age and valve
      position.
AB  - The durability (structural deterioration-free interval) after valve implantation
      with the first-generation Carpentier-Edwards porcine bioprosthesis has been
      investigated. From 1978 through 1984, 420 patients (175 male, 245 female)
      underwent valve replacement with the Carpentier-Edwards standard bioprosthesis.
      Mean age was 50.6 years (range, 13 to 77 years). Isolated mitral valve
      replacement (MVR) was performed in 198 patients (47.1%), aortic valve replacement
      (AVR) in 136 (32.4%), and double valve replacement (DVR) in 86 (20.5%). Hospital
      mortality was 32 patients (7.6%), 7.5% for MVR, 5.1% for AVR, and 11.6% for DVR.
      Mean follow-up was 10.8 years (range, 9 to 15 years) and is 96.2% completed.
      Reoperation for structural deterioration was required in 143 patients. Actuarial
      curve free from structural deterioration at 15 years is 33.0% +/- 6.5% for MVR,
      62.0% +/- 5.1% for AVR, and 44.2% +/- 8.2% for DVR (p < 0.03). Durability of the
      CE bioprosthesis for MVR was 101.6 +/- 34.5 months, 92.9 +/- 26.4 for AVR, and
      84.3 +/- 25.3 for DVR (p = not significant). The regression logistic analysis
      between age at the time of surgery and durability of the bioprosthesis showed no
      correlation for the MVR group, but with the following predictive formula for AVR
      and DVR groups of patients older than 30 years" durability = 46.05 + 0.818 x age,
      for AVR (r2 = 0.43); durability = 15.81 + 1.122 x age, for DVR (r2 = 0.52). In
      conclusion, we have found a significant difference in the behavior of the CE
      porcine bioprosthesis between the mitral and aortic position.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7646168
TI  - The Medtronic Intact xenograft: an analysis of 342 patients over a seven-year
      follow-up period.
AB  - Three hundred forty-two patients from December 1985 to January 1993 received 352
      Medtronic Intact porcine xenograft valves (zero-pressure glutaraldehyde-fixed
      with toluidine blue anticalcification agent). The follow-up was 99.4% complete
      with a mean of 3.14 years (3 months to 7.9 years). The mean patient age was 64
      years (range, 16 to 82 years) and the median age was 67 years. There were 14
      aortic valve replacement patients (11.9%) and 62 mitral valve replacement
      patients (29.2%) who preoperatively were in New York Heart Association class IV
      to V. The hospital mortality was 8.4% +/- 2.9% (aortic valve replacement, 5.9%;
      mitral valve replacement, 9.4%; tricuspid valve replacement, 7.6%). Actuarial
      patient survival at 7 years was 65% +/- 5% (aortic valve replacement, 77% +/- 5%;
      mitral valve replacement, 63% +/- 5%). At 7 years, the freedom from
      thromboembolism was 74% +/- 4%, freedom from endocarditis 93% +/- 2%, and freedom
      from reoperation 90% +/- 3%. Reoperation was required for endocarditis (7
      patients), periprosthetic leak (6), and 2 of 3 cases of structural deterioration.
      The actuarial freedom from structural deterioration at 5 years was 97% +/- 3%.
      The combined incidence of all important morbid valve-related events was analyzed
      with an actuarial freedom at 7 years of 63% +/- 3%. The durability of the
      Medtronic Intact is at least equal to that of other porcine bioprostheses. The
      relevant important time-frame of 7 to 12 years of follow-up has just begun, and
      possibly the reoperation rate for intrinsic value failure and the low incidence
      of calcification in the elderly patient may be showing improved characteristics
      of this valve. No stronger inferences are possible at this stage of the 7-year
      follow-up.

PMID- 7646169
TI  - Medtronic Intact porcine bioprosthesis: clinical performance to seven years.
AB  - The clinical performance of the Medtronic Intact porcine bioprosthesis was
      evaluated in 1,084 patients (mean age 66.4 years, range 9 to 91 years) who had a
      total of 1,099 implantations between 1985 and 1992, inclusive. There were 709
      aortic valve replacements, 297 mitral valve replacements, and 80 multiple valve
      replacements. Concomitant procedures were performed in 432 (39.3%). The age group
      distribution (years) was 35 or younger in 20 patients, 36 to 50 in 64, 51 to 64
      in 274, 65 to 69 in 225, 70 or older in 500. The total follow-up time was 2,741
      patient-years (mean, 2.5 years) and was 97.5% complete. The early mortality rate
      was 7.1% and late mortality was 3.9% per patient-year. The overall patient
      survival at 7 years was 70% +/- 3%. The freedom from major thromboembolism was
      94% +/- 1% at 7 years (p = not significant for valve positions). The freedom from
      reoperation at 7 years was 93% +/- 1%; freedom from valve-related mortality was
      89% +/- 2%. The freedom from structural valve deterioration at 7 years was 97% +/
      1% (aortic valve replacement 97% +/- 1%; mitral valve replacement 97% +/- 2%).
      The freedom from structural valve deterioration among age groups was not
      different for the overall population, aortic valve replacement, or mitral valve
      replacement. Hemodynamic assessment revealed obstructive properties for aortic
      valve replacement sizes of 21 and 23 mm and for mitral valve replacement sizes of
      25 and 27 mm.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7646170
TI  - Porcine bioprostheses in the elderly: clinical performance by age groups and
      valve positions.
AB  - Porcine bioprostheses have been recommended and used for cardiac valve
      replacement in the elderly. A review of 1,984 patients with 2,042 operations,
      performed between 1975 and 1992, has afforded a detailed evaluation of clinical
      performance by valve positions and age groups within the elderly population. The
      numbers of operations performed by age groups were 65 to 69 years, 719; 70 to 74
      years, 745; 75 to 79 years, 431; 80 to 84 years, 119; and 85 years or older, 28.
      The early mortality rate overall was 9.5% (195 patients), range 6.9% to 17.8% by
      age groups (p < 0.05), and 11.9% with concomitant procedures and 7.6% without (p
      < 0.05). The total cumulative follow-up was 10,060 patient-years (mean, 4.9
      years). The late mortality rate was 7.0%/patient-year (for age groups, 5.8% to
      13.4%/patient-year) (p = not significant). The patient survival at 15 years
      ranged from 25% +/- 4% for 65 to 69 years to 9% +/- 5% for 75 to 79 years (p <
      0.05). The freedom from valve-related complications and composites at 10 years
      revealed differences (p < 0.05) by age groups only for structural valve
      deterioration: 85% +/- 2% for 65 to 69 years versus 98% +/- 2% for 80 to 84
      years. The overall freedom from structural valve deterioration at 10 years for
      aortic valve replacement was 98% +/- 1%; for mitral valve replacement, 79% +/-
      3%; and for multiple replacement, 86% +/- 7% (p < 0.05, aortic valve replacement
      > mitral valve replacement).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7646171
TI  - Bioprosthetic valve longevity in the elderly: an 18-year longitudinal study.
AB  - The issue of bioprosthetic valve durability has become of critical importance as
      the number of elderly patients requiring valve operation has continued to
      increase. Our previous study showed bioprosthetic valve durability to be in
      excess of 83% at 13 years for patients 70 years of age and older at the time of
      implantation. There is limited follow-up data in the literature beyond this time
      point, however. Accordingly a retrospective analysis was conducted of all
      patients with bioprosthetic valves who were 70 years of age and over at the time
      of implantation. From September 1974 to April 1994, 1007 patients 70 years of age
      and over underwent valve replacement using a porcine bioprosthesis. The patients
      ranged in age from 70 to 104 years (mean, 75.6 +/- 4.3 years). There were 549 men
      (54.5%) and 458 women (45.5%). Preoperatively 98.8% of the patients were in New
      York Heart Association functional class III or IV. Operation was performed as an
      emergency in 66 patients (6.6%). The hospital mortality was 10.9% (110 patients),
      with 897 hospital survivors. There were 961 valves at risk. Follow-up extended
      from 1 month to 18.8 years (mean, 56.6 months). The cumulative follow-up is
      4232.3 patient-years. A total of 31 valves failed, 12 in the aortic position and
      19 in the mitral position (p < 0.0024). The causes of valve failure have included
      structural deterioration (16 valves), prosthetic endocarditis (7 valves),
      nonstructural dysfunction (5 valves), prosthetic thrombosis (1 valve), and other
      (2 valves).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7646173
TI  - Pregnancy and bioprostheses: influence on structural valve deterioration.
AB  - The long-term performance of bioprostheses was evaluated in women 35 years of age
      or less to determine the influence of pregnancy on structural valve
      deterioration. Between 1972 and 1992, 237 female patients received 255 biological
      prostheses. Of the total operations, 53 were performed in patients who
      experienced pregnancy (P) and 202 in patients who were never pregnant
      (nonpregnant [NP]). The mean age of the P group was 23.0 +/- 5.8 years (standard
      deviation) (12 to 34 years) and of the NP group it was 27.1 +/- 6.3 years (8 to
      35 years) (p < 0.05). The mean follow-up for the NP group was 6.8 years and for
      the P group it was 7.9 years. The late mortality was 2.26%/patient-year overall,
      2.71%/patient-year for the NP group and 0.89%/patient-year for the P group (p =
      not significant [NS]). The P group of 52 patients had 94 pregnancies: 70
      deliveries (74.5%) and 24 abortions (25.5%) (therapeutic, 14 [15%]). There were a
      total of 143 valve-related complications (P, 35; NP, 108); the majority for
      structural valve deterioration (SVD) 43% (109 patients), P 51% (27 patients) and
      NP 41% (82 patients) (p = NS). The valve-related reoperation rate paralleled the
      SVD rate at 42% (107 patients), P 51% (27 patients) and NP 40% (80 patients) (p =
      NS). The overall reoperative mortality rate was 6.0%. The interval from initial
      implant to reoperation was 99.6 +/- 3.6 months (p = NS groups P and NP).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7646172
TI  - Influence of coronary artery disease on structural deterioration of porcine
      bioprostheses.
AB  - The number of patients undergoing valve replacement and concomitant coronary
      artery bypass grafting (CABG) is increasing. To further evaluate the indications
      for the use of the porcine bioprosthesis, this retrospective comparative analysis
      of valve structural deterioration was conducted in patients with and without
      concomitant CABG. From September 1974 to October 1993, 1,567 patients underwent
      valve replacement using a porcine xenograft. The series was divided into two
      groups: patients with isolated valve replacement (VR; n = 876) and those with VR
      and CABG (VR + CABG; n = 691). Aortic valve replacement was performed in 938
      patients, mitral valve in 518, tricuspid in 2, and multiple valve replacement in
      109 patients. The mean age for the series was 70.7 years (range, 50 to 104
      years). The hospital mortality was 8.8% (138 patients). The hospital mortality
      for the VR group was 7.4% (65 deaths) and the VR + CABG group, 10.6% (73 deaths)
      p = 0.0365. There were 1,429 patients discharged from the hospital with 1,489
      valves at risk. Follow-up extended from 1 month to 17.9 years with a mean of 66.9
      months and was 98.3% complete. The cumulative follow-up was 7,927.1 patient
      years. Structural deterioration was found to be significantly greater in the VR
      group for the age category 50 to 59 years (p = 0.0121) and the 60 to 69 years (p
      = 0.0230). No significant difference in the rate of structural deterioration was
      found for the two groups for the age category 70 years and older.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7646174
TI  - Long-term experience with the Ionescu-Shiley pericardial valve.
AB  - To determine the long-term durability of the Ionescu-Shiley valve, we analyzed
      our experience with this valve at the University of Ottawa Heart Institute. To
      1988, 780 patients have had aortic valve replacement (AVR = 528) or mitral valve
      replacement (MVR = 252). Of the aortic valves, 310 were standard profile and 218
      were low profile. Of the mitral valves, 143 were standard profile and 109 were
      low profile. Actuarial survival at 10 years was as follows: AVR, 62% +/- 3%; MVR,
      58% +/- 4%; p = 0.42. At 14 years, the results were AVR, 44% +/- 1% and MVR, 46%
      +/- 5%; p = 0.40. Reoperation was required in 197 patients. Structural failure
      was present in 85% of these valves, with leaflet tears alone in 69%, tears with
      calcification in 21%, and calcification alone in 10%. Leaflet tears occurred in
      95% after AVR and in 78% after MVR (p = 0.006) and were seen in 95% of low
      profile valves and 87% of standard-profile valves (p = 0.16). The actuarial
      freedom from reoperation at 10 years was: AVR, 58% +/- 3%; MVR, 62% +/- 5%; p =
      0.49. At 13 years, these rates were 38% +/- 4% for AVR and 25% +/- 9% for MVR (p
      = 0.79). For AVR, the 10-year rate of freedom from reoperation was 57% +/- 4% for
      standard-profile valves and 57% +/- 8% for low-profile valves (p = 1.0).
      Similarly for MVR, the 10-year freedom from reoperation was 61% +/- 6% for
      standard-profile valves and 68% +/- 8% for low-profile valves.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7646176
TI  - The Carpentier-Edwards pericardial bioprosthesis: clinical experience with 600
      patients.
AB  - Carpentier-Edwards pericardial bioprostheses were implanted in 600 patients: 416
      aortic valve replacement, 115 mitral valve replacement, 6 isolated tricuspid, and
      63 multiple valve replacements. The survival rates were 70% at 10 years after
      aortic valve replacement, 62% 8 years after mitral valve replacement, and 57% at
      8 years with multiple valve replacement. Overall, 69 patients suffered one or
      more valve-related complications. The 10-year freedom rates from embolism were
      91% (aortic valve replacement), 92% (mitral valve replacement), and 89% (multiple
      valve replacement), and those from endocarditis were 95%, 93%, and 85%,
      respectively. In 18 of the 35 patients, reoperation was due to primary valve
      dysfunction. Freedom from primary dysfunction was 87% at 10 years with aortic
      valve replacement, and at 8 years, it was 79% with mitral valve replacement and
      77% with multiple valve replacement. A direct correlation was found between
      freedom from valve dysfunction and age of the patient at operation, with a 10
      year-free rate of 90% among patients older than 59 years. This bioprosthesis has
      an excellent durability up to 10 years in the aortic position. More data
      regarding its long-term durability in the mitral position are needed. It is
      currently our valve substitute of choice when a bioprosthesis is indicated.

PMID- 7646177
TI  - Durability of the Mitroflow pericardial valve at ten years.
AB  - From 1983 to 1992, 366 patients received 407 Mitroflow pericardial valves. Mean
      age was 62 +/- 14 years. Average follow-up was 72 +/- 28 months. Total follow-up
      was 1,791 patient-years. Overall survival in all patients was 77.2% +/- 2.2% at 5
      years and 56.2% +/- 6.4% at 10 years. Freedom from structural valve deterioration
      was 95% +/- 1.2% and 36.7% +/- 8.1% at 5 and 10 years for all valves, 96.9% +/-
      1.3% and 39.2% +/- 9.8% for aortic valve replacement, and 91.7% +/- 3.2% and
      36.4% +/- 10% for mitral valve replacement (p = not significant). The freedom
      from structural valve deterioration in patients older than 70 years of age was
      100% and 93.9% +/- 5.8% at 5 and 10 years, respectively. At 10 years, linearized
      rate of thromboembolism was 0.73% +/- 0.2% per patient-year and freedom from
      valve-related mortality for all valves was 88.8% +/- 2.8%. The best indication
      for the implantation of a Mitroflow valve is mitral or aortic disease in patients
      more than 70 years of age.

PMID- 7646175
TI  - Carpentier-Edwards pericardial bioprosthesis in aortic position: long-term follow
      up 1980 to 1994.
AB  - Aortic valve replacement with Carpentier-Edwards pericardial bioprosthesis was
      associated with excellent midterm clinical results. Long-term evaluation,
      however, remained to be determined. We reviewed the first 124 patients who
      underwent aortic valve replacement with a Carpentier-Edwards bioprosthesis at the
      Hopital Broussais between 1980 and 1985. There were 67 males (54%) and 57 females
      (46%). The mean age at operation was 65 years (range, 18-83 years). The operative
      mortality (30 days) was 4%. All but 2 patients were followed up for an average of
      7.7 years and a total of 973 patient years. There were 45 late deaths
      (4.7%/patient-year) of which 16 were valve-related (1.7%/patient-year). The
      actuarial survival rate was 49.9% at 12 years. The actuarial rate for freedom
      from valve-related mortality was 78.3% at 12 years. There were 7 thromboembolic
      events in 5 patients and 3 anticoagulation-related hemorrhages. Freedom from
      structural valve deterioration was 100% at 12 years and 83.3% at 13 years. We
      conclude that implantation of Carpentier-Edwards pericardial bioprosthesis in
      aortic position is associated with an excellent long-term clinical outcome. It is
      believed that the improved results of this valve result from the following
      original features: fully flexible stent, distensible struts, infrastent tissue
      mounting, optimal tissue orientation, and improved preservation.

PMID- 7646178
TI  - Mitroflow pericardial bioprosthesis: clinical performance to ten years.
AB  - The Mitroflow pericardial bioprothesis, a second generation pericardial
      prosthesis, has clinical performance assessment to 10 years. This bioprosthesis
      was used in 445 operations in 445 patients between 1982 and 1992 inclusive (mean
      age, 59.1 years; age range, 19 to 94 years). There were 253 aortic valve
      replacements (AVR), 155 mitral valve replacements (MVR), 31 multiple valve
      replacements (MR), and 6 tricuspid valve replacements. Concomitant procedures
      were performed in 40 patients (14.2%). The age group distributions (years) were
      less than or equal to 35 years, 28 patients; 36 to 50 years, 79; 51 to 64 years,
      167; 65 to 69 years, 70; and 70 years or more, 101 patients. The total follow-up
      was 1,524 patient-years (mean, 5.4 years), 96% complete. The early mortality was
      6.3%/patient-year (28 patients) and the late mortality was 4.1%/patient-year (96
      patients). Concomitant procedures did not influence either early or late
      mortality (p = not significant [NS]). The overall patient survival at 10 years
      was 58% +/- 5% (p = NS by valve position). The overall freedom from structural
      valve deterioration (SVD) at 8 years was 69% +/- 3% and at 10 years, 45% +/- 7%;
      and at 8 years AVR 80% +/- 4%, MVR 58% +/- 6%, and MR 38% +/- 11% (p < 0.05, AVR
      > MVR > MR). The freedom from thromboembolism (TE) was 87% +/- 2%, overall at 10
      years, and was not different by valve position (p = NS).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7646179
TI  - Intermediate clinical results after aortic valve replacement with the Carpentier
      Edwards pericardial bioprosthesis.
AB  - From January 1986 through December 1993, 482 patients underwent aortic valve
      replacement with the Carpentier-Edwards pericardial bioprosthesis at our
      institution. Patients ranged in age from 26 to 87 years (mean, 72.5 +/- 7.1
      years), and 59.8% of them were men. Pure or predominant aortic stenosis was the
      indication for operation in 80.1% of the patients. Most (75.4%) of the patients
      were in New York Heart Association functional class III or IV preoperatively
      because of dyspnea. Isolated aortic valve replacement was performed in 265
      patients (55.0%). The most frequent concomitant procedure was aortocoronary
      bypass grafting (38.4%). All patients were followed up for as many as 7 years
      postoperatively (average, 1.7 +/- 1.7 years). Twenty-six patients (5.4%) died
      within 30 days postoperatively; 53 patients died during the remainder of the
      follow-up period. The actuarial survival rate was 74.0% +/- 3.6% at 5 years and
      59.7% +/- 7.5% at 7 years postoperatively. There were 12 valve-related deaths,
      and these were due to endocarditis (n = 3), thromboembolism (n = 5),
      anticoagulant-related hemorrhage (n = 2), reoperation necessitated by structural
      deterioration (n = 1), and sudden death (n = 1). After 7 years, the freedom from
      thromboembolic events was 86.6% +/- 3.8%, the freedom from anticoagulant-related
      hemorrhage was 98.0% +/- 0.9%, and the freedom from reoperation was 90.9% +/-
      8.3%. There was only one structural failure, and this occurred at 6 years
      postoperatively.

PMID- 7646180
TI  - Surgical correction of aortic disease using intraluminal, crimped bovine
      pericardial graft.
AB  - We propose the use of a crimped bovine pericardial graft joined to a rigid and
      grooved ring for the treatment of aortic dissections and aneurysms. This device
      was developed to support common tubular vascular prostheses of any material,
      length, diameter, or form, transforming them into intraluminal ones during the
      surgical procedure. During March 1989 to May 1994, 74 patients underwent an
      operation on the aorta in which this intraluminal ring, prepared from a tubular
      prosthesis of bovine pericardium, was used. Twenty-seven patients had an acute
      type A aortic dissection, 6 had an acute type B aortic dissection, 10 had
      annuloaortic ectasia, 6 had a descending aortic aneurysm, 3 had a
      thoracoabdominal aneurysm, and 22 had an abdominal aneurysm. The global mortality
      rate of 10.8% in the immediate postoperative period cannot be related to the
      surgical technique or the type of prosthesis used. We conclude from our findings
      that this modification of the sutureless intraluminal graft, which allows it to
      be used to replace diseased segments of the aorta, affords the quickest and
      simplest means of repair and is attended by the least likelihood of anastomotic
      complications.

PMID- 7646182
TI  - Do donor or recipient species influence calcification of bioprosthetic tissues?
AB  - To determine whether donor or recipient species influence calcification of
      bioprosthetic tissues, glutaraldehyde-treated valvar or pericardial specimens
      from different species (calf, sheep, pig) were subcutaneously implanted in
      different animals (rat, rabbit, cow, hen). Significant differences in the rate of
      calcification of the implanted specimens were found, which have important
      practical and theoretical implications for the development of valvular
      bioprostheses.

PMID- 7646181
TI  - Physicochemical characterization of natural and bioprosthetic heart valve
      calcific deposits: implications for prevention.
AB  - This investigation was performed to provide a comprehensive physicochemical
      characterization of calcific deposits (CDs) that form on human heart valves under
      various pathological conditions. We examined and characterized CDs associated
      with aortic stenosis on congenitally bicuspid valves (n = 10), degenerative
      aortic stenosis on valves with previously normal anatomy (n = 10), and rheumatic
      aortic (n = 10) and mitral (n = 10) stenosis. Native and deproteinated CDs
      underwent chemical analysis and structural characterization, whereas
      deproteinated CDs were measured for thermodynamic solubility. The CDs in valvular
      heart disease were microcrystalline apatitic products containing substantial
      amounts of sodium, magnesium, carbonate, fluoride, and organic fraction. The
      properties of natural heart valve CDs were compared with those of previously
      measured CDs that form on or in heart valve bioprostheses. Compared with
      bioprosthetic valve CDs, natural valve CDs have a higher ratio of calcium to
      phosphorus, higher crystallinity, and lower solubility. These differences
      indicate that natural heart valve CDs appear to comprise a more mature
      biomineral. If the formation of mature CDs proceeds through transient stages
      involving unstable precursors, then the main strategy for prevention of calcific
      deterioration of bioprosthetic heart valves would be the development of locally
      applied long-term inhibitors that both (1) suppress nucleation and growth of more
      soluble precursors and (2) inhibit subsequent augmentation of less soluble CDs.

PMID- 7646183
TI  - Calcium mitigation in bioprosthetic tissues by iron pretreatment: the challenge
      of iron leaching.
AB  - Preliminary studies in our laboratory have shown that iron pretreatment of
      glutaraldehyde-preserved tissues inhibited calcification. The present study was
      designed to further investigate this finding and to optimize the technique.
      Porcine valve tissue and bovine pericardium preserved in glutaraldehyde and
      pretreated by iron at different concentrations and incubation times were
      implanted either subcutaneously in rats or as a mitral valve substitute in sheep.
      Compared with control groups, calcification was markedly inhibited in the groups
      pretreated with Fe3+. There was a direct correlation between the degree of
      calcification and the iron content within the tissue. A minimal iron content
      within the tissue of 0.5% for porcine valve tissue and 0.2% for pericardial
      tissue was found to be necessary for calcium mitigation. A progressive leaching
      of Fe3+ was observed that could be stabilized by using a higher concentration of
      iron in the solution and or by additional pretreatment in glutaraldehyde at high
      temperature, but only for subcutaneously implanted tissues. By contrast, leaching
      was faster and more complete in the iron-pretreated tissue valves placed in the
      circulating blood environment, therefore resulting in calcified valves.
      Pretreatment in glutaraldehyde at high temperature (50 degrees C) alone was able
      to mitigate calcification in both subcutaneous and circulating blood
      environments, a new finding that may lead to an improved method for
      glutaraldehyde preservation of tissues.

PMID- 7646184
TI  - Prevention of calcification of heart valve bioprostheses: an experimental study
      in rat.
AB  - To eliminate highly antigenic substances, bovine pericardium was washed in 5%
      sodium chloride (NaCl) for 24 hours, followed by incubation in trypsin for 40
      minutes. To achieve adequate fixation, NaCl-trypsin-treated pericardium was
      preserved in glutaraldehyde (GA) solution with gradually increasing
      concentrations from 0.1% to 0.25%. To inactivate the free aldehyde groups and
      residual GA on the surface of the implant, NaCl-trypsin-GA-treated pericardial
      samples were posttreated separately with 1% lysine, 8% monosodium glutamate, and
      4% chitosan. Fresh (untreated) and 0.1%, 0.2%, and 0.625% GA-treated and NaCl
      trypsin-GA-treated pericardial specimens were prepared for comparative study. All
      samples were implanted subdermally in rats for 2, 4, 8, and 12 weeks for
      calcification studies. Morphologic and chemical analyses showed mild
      calcification in fresh pericardia (Ca, 10.5 +/- 1.25 micrograms/mg, von Kossa +)
      and in glutamate-posttreated pericardia (Ca, 11.5 +/- 3.45 micrograms/mg, von
      Kossa +). Calcium was practically undetectable in chitosan-posttreated implants
      (Ca, 1.1 +/- 0.27 micrograms/mg, von Kossa 0), whereas severe calcification was
      noticed in the rest of the samples (mean Ca greater than 200.0 micrograms/mg, von
      Kossa ) at 12 weeks. This study suggests that posttreatment with an amino
      compound such as chitosan would prevent the calcification of GA-treated
      bioprostheses at an early implantation stage, but elimination of antigenic
      factors and adequate GA fixation would prevent tissue degeneration, thus enabling
      the prosthesis to function over a long period.

PMID- 7646185
TI  - Time-dependent effect of glutaraldehyde on the tendency to calcify of both
      autografts and xenografts.
AB  - To determine mechanisms responsible for the reduced calcification in short-term
      glutaraldehyde (Glu)-treated autologous pericardial bioprostheses, we studied the
      time effect of Glu on subsequent calcification and differences in calcification
      of autograft and xenograft implants in a rat subcutaneous implantation model. In
      experiment 1, four groups of bovine pericardial pieces (1 cm2) were prepared: (A)
      fresh bovine pericardium without Glu, (B) with 15-minute Glu, (C) with 60-minute
      Glu, and (D) with 120-minute Glu. Seven young male Sprague-Dawley rats were used;
      each received four bovine pericardial pieces from group A, B, C, or D for
      subcutaneous implantation. Calcium content of the implants (microgram/mg dry
      weight) 45 days later was 4.8 +/- 2.9, 29.8 +/- 13.6, 106.3 +/- 13.7, and 176.3
      +/- 85.5 in groups A, B, C, and D, respectively (p < 0.05 between any two
      groups). Experiment 2 used 8 young male Sprague-Dawley rats from different
      mothers. Each received five subcutaneous skin implants. The five skin implants
      were prepared as follows: (1) fresh self skin, (2) self skin with 30-minute Glu,
      (3) self skin with 48-hour Glu, (4) fresh skin of others, and (5) skin of others
      with 48-hour Glu. After 45 days of implantation, the calcium content of the
      implants was 1.4 +/- 1.1, 57.9 +/- 35.4, 142.7 +/- 61.4, 1.5 +/- 1.1, and 94.9 +/
      24.1 micrograms/mg dry weight in groups 1, 2, 3, 4, and 5, respectively (p <
      0.05 for 1 versus 2, 3, or 5; 2 versus 3, 4, or 5; 3 versus 4; and 4 versus
      5).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7646186
TI  - Relevance of immunologic reactions for tissue failure of bioprosthetic heart
      valves.
AB  - The use of biologic heart valve prostheses is decreasing because of the high
      incidence of failure of these bioprostheses resulting from tissue degeneration or
      tearing. Immunologic reactions might play a decisive role in this process. The
      present experimental and clinical studies were conducted to investigate the
      relevance of immunologic reactions to the tissue failure of glutaraldehydetanned
      bovine pericardial and porcine valves. Specimens of the two different types of
      valve material were implanted in the abdominal muscles of rats. Enzyme-linked
      immunosorbent assays and tritiated thymidine incorporation tests were performed
      to detect specific antibodies and activated T cells. All specimens were studied
      histologically. Identical enzyme-linked immunosorbent assays and tritiated
      thymidine incorporation tests were performed in 29 patients with bioimplants and
      in 48 controls. Twenty explanted bioprostheses were investigated using histologic
      and immune histologic methods. The results of the enzyme-linked immunosorbent
      assays and lymphocyte proliferation tests showed that glutaraldehyde-tanned
      bovine pericardial valves can provoke cellular and humoral immunologic reactions
      in rats and human beings. In explanted bovine valves, macrophages were found
      invading and degrading implant collagen, starting from surface lesions. The
      combination of the formation of mechanical lesions, the development of cellular
      infiltrates, and collagen disruption strongly indicates that initial surface
      lesions initiate the immunologic reactions in bovine pericardial valves as the
      result of the exposure of incompletely tanned collagen. These immune responses
      might accelerate tissue degeneration. Porcine valves do not provoke immunologic
      reactions.

PMID- 7646187
TI  - Acellular matrix: a biomaterials approach for coronary artery bypass and heart
      valve replacement.
AB  - We have developed a multistep detergent-enzymatic extraction process (involving
      hypotonic and hypertonic solutions, the detergents octyl-phenoxy
      polyethoxyethanol and sodium dodecyl sulfate, as well as DNAse and RNAse) which,
      while inhibiting autolysis, removes all cells from tissues and, with them,
      cellular antigens together with lipids and more soluble glycosaminoglycans. What
      remains is acellular matrix with the structural proteins well conserved and
      normally arranged. Canine arteries extracted to acellular matrix were implanted
      as coronary artery bypass allografts in a canine model, without the use of
      cardiopulmonary bypass, and compared with autogenous saphenous veins. Of nine
      pilot acellular matrix implants, four were patent, as compared with four of seven
      saphenous vein grafts. All occlusions in both graft types occurred acutely soon
      after implantation, with almost all patent grafts followed up for 6 months. The
      acellular matrix allografts showed no inflammation and only minimal cellular
      repopulation. This model needs further development, but appears promising for
      preclinical evaluation. Canine aortic and pulmonic valves extracted to acellular
      matrix using a modification of our extraction process, eliminating the detergent
      sodium dodecyl sulfate, were implanted heterotopically as allografts in the left
      main pulmonary artery in dogs, a location chosen to avoid the need for
      cardiopulmonary bypass. At 1 month, two-dimensional echocardiography of six
      implants showed leaflet motion and 3- to 5-mm Hg transvalvular gradients. Explant
      histology of four valves at 1 month showed no inflammation, cellular repopulation
      at the base of the valve, and partial endothelialization.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7646188
TI  - The hybrid xenograft/autograft bioprosthetic heart valve: in vivo evaluation of
      tissue extraction.
AB  - The major functional problem with bioprostheses is poor long-term durability.
      Bioprosthetic valves fail because of calcification and mechanical fatigue, both
      of which result from the glutaraldehyde fixation process. In an effort to develop
      a biologically active, non-cross-linked bioprosthetic valve, we devised a
      cellular extraction process. We tested the mechanical integrity of the processed
      valves and cultured both human and porcine cells on this material. To test the
      potential for calcification, we implanted strips of fresh, extracted, and
      glutaraldehyde-treated porcine heart valve tissue subcutaneously into 3-week-old
      Sprague Dawley rats for 21 days. We used atomic absorption spectroscopy to
      measure the extent of calcium accumulation and histopathologic assessment to
      evaluate the antigenic response. We found that the cell extraction process
      significantly reduced the propensity of the material to calcify in vivo (mean +/-
      standard deviation, 4.12 +/- 1.02 mg/g calcium extracted versus 10.75 +/- 3.9
      mg/g calcium fresh versus 79.6 +/- 18.3 mg/g calcium glutaraldehyde fixed) but
      increased the antigenicity, as evidenced by increased cellular activity and
      resorption. Although they may reduce calcification, conventional detergent-based
      cell extraction techniques do not completely remove porcine aortic valve antigens
      and may in fact increase the antigenicity of the valve cusp material.

PMID- 7646189
TI  - In vitro endothelialization of photooxidatively stabilized xenogeneic
      pericardium.
AB  - The possibility of improving the performance of heart valve bioprostheses and
      vascular biografts by means of preendothelialization with cultured autologous
      cells has been suggested. Such culture techniques are available, but the
      glutaraldehyde-preserved heart valve prostheses used clinically appear cytotoxic.
      Recently, dye-mediated photooxidation has been reported to stabilize pericardial
      tissue, possibly through the cross-linking of collagen fibrils. We have seeded
      cultured adult human saphenous vein endothelial cells (HSVECs) onto
      photooxidatively stabilized tissue and investigated the morphologic
      characteristics 7 days later. A confluent lining of cultured HSVECs similar to
      native endothelium was demonstrated by scanning electron microscopy. The presence
      of von Willebrand's factor, an integrin located at the interendothelial cell
      contacts (PECAM/CD 31), and the basement membrane component collagen type IV was
      demonstrated using monoclonal antibodies. The results were similar for the HSVECs
      seeded onto both bovine and porcine pericardial tissues. The results clearly
      indicate that the dye-mediated photooxidation technique produces a tissue that is
      cell compatible. Provided the HSVECs remain attached and retain antithrombotic
      and antiinflammatory properties, this appears to be a feasible way of
      endothelializing bioprosthetic heart valves before implantation.

PMID- 7646190
TI  - Glutaraldehyde fixation alters the internal shear properties of porcine aortic
      heart valve tissue.
AB  - Glutaraldehyde fixation noticeably alters the mechanical properties of porcine
      aortic valve tissue, subsequently affecting the function and durability of these
      tissues when used as prosthetic heart valves. Traditional uniaxial tensile
      testing techniques do not fully define the mechanical properties and we have
      devised a new approach to examine the important shear properties of the tissue.
      Altered shear properties would change the response of the valve tissue as it
      flexes open and closed. An apparatus combining a high-precision linear actuator
      with a gram-sensitive load cell was used to measure the shear characteristics of
      circular punch specimens taken from the center of each valve cusp. The tissue
      parameters measured showed significant differences between the fixed and fresh
      tissues. Glutaraldehyde-fixed tissue (n = 16) was about 100 times as stiff as
      fresh tissue (n = 32) between shear strain values of 0 and 0.2. The fixed tissue
      also had stress relaxation rates about 60% those of the fresh cusps and had about
      70% of the hysteresis loss seen in fresh tissue. These results demonstrated the
      significant effects of glutaraldehyde fixation on the properties of porcine
      aortic valve cusp when tested in shear. Such changes could lead to altered tissue
      function and may increase internal stresses during opening and closing,
      contributing to valve fatigue.

PMID- 7646191
TI  - Biaxial strain analysis of the porcine aortic valve.
AB  - The function of a bioprosthetic heart valve is determined largely by the material
      properties of the valve cusps. The mechanics of natural and bioprosthetic valve
      cusps have been studied extensively using uniaxial tensile testing. This type of
      testing, however, does not duplicate the natural biaxial loading condition. Whole
      valve biaxial testing therefore is preferred. The objective of the present study
      was to investigate the heterogeneity of the valve cusps by mapping out the
      regional variability of the biaxial strain versus pressure relationship. Whole
      porcine aortic valves were mounted horizontally, submerged in physiologic saline
      solution at 37 degrees C, and pressurized in the range of 0 to 130 mm Hg of
      pressure. The ventricular side of the cusps were marked with black dots and the
      three-dimensional position of these dots was recorded together with the aortic
      pressure. By calculating the distance between the dots in the radial and
      circumferential directions in different regions, the local strain versus pressure
      relationship was determined. The results showed that the valve cusp material
      strained by 23% +/- 0.8% in the radial direction and 10.0% +/- 0.5% in the
      circumferential direction before lock-up. It was also found that while the valve
      cusp was highly anisotropic in the central region, the basal region was
      relatively isotropic, and the cusp as a whole was asymmetrical in its
      distensibility.

PMID- 7646192
TI  - Bioprosthetic valve tissue viscoelasticity: implications on accelerated pulse
      duplicator testing.
AB  - Most of our knowledge of heart valve mechanics has been gained from low strain
      rate studies much lower than physiologic levels. Using a high-speed materials
      testing system, we compared the low and high strain-rate viscoelastic behavior of
      porcine aortic valve cusps at extension rates of up to 40 mm/s. Circumferential
      and radial strips were stretched and then held in their stretched configuration
      to measure their "stress-relaxation" behavior. During low strain-rate stretching,
      only 6% of the initial stress dissipated or relaxed after 1 second, whereas 25%
      of the stress dissipated during high strain-rate stretching. This considerable
      difference in stress relaxation suggests a rate-dependent viscoelastic behavior
      that has not been accounted for in valve design and may have important
      implications for accelerated pulse testing. Even though the valve cusp is loaded
      for only 0.4 seconds during each heartbeat, at least 15% of the stress may relax
      over that period. During accelerated pulse testing, however, sufficient time may
      not be available to allow the tissue fibers to relax back to their natural state
      before the subsequent loading cycle, leading to a higher baseline preload. In
      addition, because valve tissue is not given sufficient time to relax before the
      next cycle, pulse testing subjects the valves to lower-magnitude cyclic stresses
      than does physiologic loading. Because both the baseline preload and the
      magnitude of cyclic stresses may lead to early fatigue failure, accelerated wear
      testing may either overestimate or underestimate valve durability. Clearly, the
      mechanism of stress-induced failure of biologic tissues must be elucidated before
      too much validity is placed on pulse duplicator studies.

PMID- 7646193
TI  - Longitudinal and radial distensibility of the porcine aortic root.
AB  - The aortic root has been shown to be a highly distensible structure. The function
      of the aortic valve is intimately related to the expansion of the aortic root,
      and current nonexpansible stent designs may affect its performance. We therefore
      measured the radial and longitudinal expansion of the porcine aortic root as a
      function of pressure in both a static pressurization model and in an isolated
      working heart model. The radial and longitudinal expansion of the aortic root was
      measured using a custom-built digital sonomicrometer. Multiple ultrasonic
      crystals were sutured exterior to the commissures and along the length of the
      aortic root, and their separation was tracked at varying aortic pressures. In
      static testing, we found that commissural separation at zero pressure was 26% +/-
      7% (mean +/- standard deviation) less than at 120 mm Hg, whereas the longitudinal
      distance between the base of the valve and the commissures decreased by 11% +/-
      9%. Approximately one quarter of the total dimensional change occurred over the
      physiologic range of 80 to 120 mm Hg. In the isolated porcine heart model, we
      measured a greater distensibility than in the static tests. For example, at
      aortic pressures of 120/80 mm Hg (systolic/diastolic), the diameter of the aortic
      root would be 22% +/- 6% less at 80 mm Hg than at 120 mm Hg. The longitudinal
      dimensions would be 15% +/- 8% less at 80 mm Hg than at 120 mm Hg. We conclude
      that the aortic root contracts significantly when depressurized, as during valve
      replacement surgery, and that the in vivo distensibility of the aortic root is
      much greater that what is generally measured in vitro. These results suggest that
      dimensional changes in the implanted prosthetic valve and the recipient aortic
      root must be considered to achieve both optimal valve orifice and, in the case of
      distensible valves such as allografts, a proper valve cusp geometry.

PMID- 7646194
TI  - Aortic valve cusp microstructure: the role of elastin.
AB  - The aortic valve cusp is a three-layered structure, composed of differing amounts
      of collagen, elastin, and glycosaminoglycans. Little quantitative information is
      presently available on the amount, location, orientation, and overall structure
      of these constituents, particularly of elastin. We developed a technique to
      isolate aortic valve elastin in a morphologically intact state. Whole leaflets
      were digested in 0.1 N sodium hydroxide solution at a temperature of 75 degrees
      C. Both scanning electron microscopy and computerized three-dimensional
      reconstructions of serial sections showed a well-defined honeycomb or spongelike
      structure, suggesting that elastin forms a matrix that surrounds and links the
      collagen fiber bundles. This relationship between collagen and elastin is further
      supported by the naturally wavy configuration of the valve cusps, permitting
      elongations of 40%, even though collagen fibrils typically strain to 1% to 2%
      before fracture. Elastin likely acts to return collagen fibers back to their
      undeformed state, maintaining rest geometry.

PMID- 7646195
TI  - Perioperative assessment of aortic homograft, Toronto stentless valve, and
      stented valve in the aortic position.
AB  - We investigated aortic valve hemodynamic performance and perioperative left
      ventricular function in 50 patients (mean [+/- SD] age, 64 +/- 9 years; 34 men,
      16 women) undergoing elective aortic valve replacement, using an aortic homograft
      (n = 20), a Toronto stentless porcine valve (n = 20), or a stented bioprosthesis
      (n = 10), by transesophageal echocardiography combined with high-fidelity cavity
      pressure recordings and thermodilution cardiac output measurements. Thirty-nine
      patients had aortic stenosis; 11 had predominant regurgitation. Thirteen patients
      with concomitant coronary artery stenosis underwent grafting. Left ventricular
      mass index in all patients was 280 +/- 110 g/m2. The transvalvular pressure drop
      and energy consumption were significantly higher with stented than stentless
      valves (5 with aortic homograft and 11 with Toronto valve, with matched age and
      valve size; 20 +/- 12 versus 3 +/- 9 mm Hg; 21% +/- 13% versus 8% +/- 8%, both p
      < 0.01). However, there was no difference in these variables between the Toronto
      valve and the aortic homograft (3 +/- 12 versus 2 +/- 10 mm Hg; 5% +/- 14% versus
      2% +/- 12%, both p > 0.05), although the Toronto valves (normalized to body
      surface area) were larger than the aortic homografts (14.4 +/- 1.9 versus 12.6 +/
      1.8 mm/m2, p < 0.01). There was no significant difference in left ventricular
      stroke volume index or stroke work index in the systemic circulation, either
      between stentless and stented valves or between aortic homografts and Toronto
      valves, although the cross-clamp time required to insert a stentless valve was 20
      minutes longer than that for a stented valve.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7646197
TI  - Composite stentless xenograft for aortic valve replacement: clinical evaluation
      of function.
AB  - At The Prince Charles Hospital, 55 patients have received the composite porcine
      aortic xenograft (model 300, Cryolife-O'Brien valve; Cryolife International,
      Atlanta, GA; formerly the Bravo Cardiovascular Inc valve) for aortic valve
      replacement since December 1992. Associated procedures were required in 50% of
      patients (coronary artery bypass grafting in 25 patients). Hospital and "late"
      mortality have been 0%. Follow-up has been 100% complete. The median patient age
      was 74 years (range, 59 to 88 years). One permanent intraoperative
      cerebrovascular accident and two early thromboembolic events (both associated
      with acute atrial fibrillation) have constituted the only three morbid events.
      Serial echocardiography at 1 week, 6 months, and 1 year has shown a mean gradient
      of 9 mm Hg. A small number of patients have a "trivial" degree of valve
      incompetence. No progression of either gradient or incompetence is evident. The
      clinical state of 54 of these patients is most satisfactory. However, long-term
      surveillance is necessary to determine the 8- to 10-year durability of this
      stentless xenograft.

PMID- 7646196
TI  - Early experience with the Toronto stentless porcine valve.
AB  - Stentless porcine valves in the aortic position offer many theoretic advantages,
      but their clinical performance has not been adequately defined. We evaluated the
      clinical and echocardiographic results of 103 patients who had aortic valve
      replacement with the Toronto stentless porcine valve over a 2-year period. There
      were 67 men with a mean age of 68 years. The predominant native valve lesion was
      aortic stenosis (64%), and 4 patients had prosthetic valve dysfunction. Forty-two
      patients had concomitant procedures. The 30-day mortality rate was 3.3% (n = 2)
      for isolated valve replacement and 5.8% (n = 6) for the series. The sole
      determinant of early death was poor left ventricular function. There were three
      late deaths due to non-valve-related complications over a median follow-up of
      11.87 months. In addition, prosthetic valve endocarditis developed in 1 patient,
      necessitating a homograft valve replacement at 6 weeks. Doppler echocardiography
      performed at 3 to 6 months showed low peak and mean transvalvular gradients, with
      no substantial change at 1 year. None of the patients showed signs of clinically
      significant aortic regurgitation, although echocardiography demonstrated trivial
      or mild regurgitation in 12 patients at discharge or early follow-up, which was
      less marked or absent at 1 year. We conclude that the Toronto stentless porcine
      valve appears to offer promising early results.

PMID- 7646198
TI  - The Cryolife-O'Brien composite aortic stentless xenograft: surgical technique of
      implantation.
AB  - The Cryolife-O'Brien (Cryolife International, Atlanta, GA; formerly the Bravo
      Cardiovascular Inc valve) stentless porcine aortic xenograft (model 300) is a
      composite valve of three noncoronary leaflets, symmetric in configuration with a
      broad coaptive leaflet surface. Because the valve has only a superior aortic wall
      cuff, a single continuous suture line of 3/0 Prolene provides a rapid, safe
      implantation. The ideal recipients are elderly patients, who benefit from a short
      cardiopulmonary bypass period and whose degenerative calcific valves are
      generally symmetric. The step-by-step technique of implantation is outlined, as
      are the principles of maintaining symmetry during implantation. The stentless
      valve has been used for aortic valve replacement in 55 elderly patients, with no
      deaths and minimal morbidity.

PMID- 7646199
TI  - The O'Brien-Angell stentless porcine valve: early results with 150 implants.
AB  - From August 1991 to June 1994, 150 patients underwent aortic valve replacement
      with the O'Brien-Angell stentless porcine xenograft (Bravo Cardiovascular Model
      300, Cryolife, Atlanta, GA). To establish trends we analyzed three consecutive
      groups of 50 patients. We found significant differences in low postoperative
      gradients (mean < or = 10 mm Hg): 24% in group 1, 42% in group 2, and 96% in
      group 3. Comparing groups 1 and 3, gradients were significantly lower in all
      valve sizes. The difference is credited to better supraannular positioning of the
      valve, which is the key to the learning curve. Trivial central regurgitation was
      present in the three groups at 6%, 12%, and 0%, respectively. Peripheral
      regurgitation was trivial in 6%, 8%, and 0%, and mild to moderate in 4%, 2% and
      0%, respectively. Seventy-eight of 107 patients with an available follow-up
      exceeding 1 year had noninvasive controls. Two early cases with moderate
      perivalvular leaks evolved to moderately severe leaks. Two valves were explanted.
      The O'Brien-Angell stentless valve is easy to handle and correct supraannular
      positioning provides excellent hemodynamic results.

PMID- 7646200
TI  - Aortic valve replacement: is the stentless xenograft an alternative to the
      homograft? Early results of a randomized study.
AB  - From November 1992 to October 1993 we randomized 101 patients over 60 years of
      age undergoing elective aortic valve replacement, with or without concomitant
      coronary artery bypass grafting, to receive either a cryopreserved aortic or
      pulmonary homograft (n = 38) or a stentless porcine aortic valve xenograft
      (Edwards Prima 2500) (n = 63). The majority of all valves (92%) were inserted
      freehand in the subcoronary position. Six homografts (16%) were implanted as a
      free-root replacement and two xenografts (3%) were used as a mini root. There
      were four in-hospital deaths (4%), three in the homograft group and one in the
      xenograft group (homograft, 7.9% versus xenograft, 1.6%; p = not significant).
      Forty-one patients were followed at 3- to 6-month intervals for 9 +/- 2 months (3
      to 14 months) and valve pathology was assessed routinely by means of color flow
      Doppler echocardiography. Two patients in the homograft group developed new
      aortic insufficiency grade II; all others remained with trivial or no valve
      incompetence. The mean gradient remained unchanged to immediate postoperative
      measurements (homograft, 5 +/- 1 mm Hg versus xenograft, 11 +/- 4 mm Hg; p <
      0.001). Despite a slightly higher transvalvular gradient, xenografts achieved
      excellent initial results when compared to homografts. Ease of implantation and
      freedom from thromboembolism indicate that xenografts can be an acceptable
      alternative to homografts, particularly in older patients with small aortic
      annuli. Long-term studies assessing the durability of the xenograft are necessary
      for final evaluation.

PMID- 7646201
TI  - Aortic valve replacement with the freestyle stentless xenograft.
AB  - We performed aortic valve replacement with the Free-style stentless xenograft in
      55 consecutive patients requiring a bioprosthesis. Thirty-four were male and 21
      female, and all were in New York Heart Association class III to V. Ages ranged
      from 44 to 87 years (median, 74 years). Fifteen patients required coronary bypass
      grafts. One required mitral valve replacement (after attempted repair) and
      another needed repair of both the mitral and tricuspid valves. Four were
      reoperations. Implantation involved two-thirds transection at the aortic
      sinotubular junction and insertion of the xenograft cylinder into the aortic
      sinuses. Ischemic times ranged from 34 to 58 minutes for isolated aortic valve
      replacement and up to 79 minutes for aortic plus mitral valve replacement. Two
      patients died in the hospital of left ventricular failure. Survivors underwent
      echocardiographic assessment of systolic gradients. The mean gradients for valve
      sizes of 21, 23, 25, and 27 cm were 13, 10, 8, and 6.5 mm Hg, respectively. No
      patient had more than trivial regurgitation. One died late of left ventricular
      failure. The Free-style stentless xenograft is user friendly and can be employed
      in a calcified root. The "cylinder within a cylinder" method is simple and
      reproducible and avoids aortic regurgitation. Follow-up has shown excellent
      hemodynamic function and decreasing gradients.

PMID- 7646202
TI  - From aortic cusp extension to valve replacement with stentless pericardium.
AB  - Between 1988 and 1994, 82 consecutive patients (median age 24 years) underwent
      reconstruction of the aortic valve with glutaraldehyde-treated pericardium.
      Simultaneously, 29 of 30 mitral valves were repaired. The first 27 patients
      underwent resection of the free edges and suture of a single strip of bovine
      pericardium. Transient ischemic changes suggested the need for a change in
      technique. The subsequent 55 patients underwent total valve reconstruction with
      an autologous pericardium fixed with glutaraldehyde in the appropriate shape and
      size according to the patient's aortic annulus. There were one in-hospital and
      three late deaths. No patient received anticoagulation, and no embolic events
      were detected. Nine patients required reoperation as a result of failure of
      mitral valve repair in 4 and severe aortic regurgitation in 5 (endocarditis [n =
      2], commissural tear [n = 1], root dilation [n = 1], calcification of one bovine
      cusp [n = 1] at 58 months). There were no reoperative deaths. Complete linear
      echocardiographic follow-up of these patients showed low gradients, valve
      competence, and no progressive deterioration. No difference between techniques
      was detected.

PMID- 7646203
TI  - New evolution in mitral physiology and surgery: mitral stentless pericardial
      valve.
AB  - The human adult mitral valve, with a mean diastolic area of up to 7.6 cm2, excess
      leaflet surface area for coaptation in systole, mitral annulus-papillary muscle
      continuity, and systolic constriction of the posterior left ventricular wall
      around the mitral annulus functions in concert with other components of the left
      side of the heart. Mitral valve replacement with an artificial valve that
      interferes with the normal physiology could account for less than adequate late
      results. A stentless biologic mitral valve substitute has been designed,
      constructed, and tested. The size of the valve is selected according to the
      circumference of the excised valve within certain limits. The valve is
      manufactured of two square or trapezoidal pieces of selected stabilized human
      autologous or bovine pericardium. The pericardial pieces are sutured together by
      their lateral margins, thus creating a frusto-conical valvular body. The upper
      circumference of the valvular body is sutured at the mitral annulus and the lower
      margin with the new chordae is attached by suture at each papillary muscle. In
      vitro testing of six stentless bovine pericardial valves in a Rowan-Ash fatigue
      tester at 1,200 cycles/min revealed a durability of more than 320 million cycles.
      Clinical use of described technique initiated in 1989 was performed in 18
      patients by one surgeon (30 patients in the same institution). The mean valve
      size was 29 mm circularized diameter. There was no mortality in this group of
      patients up to 70 months of follow-up. Valve competence was obtained in every
      case by adequate sizing of the valve.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7646204
TI  - Surgical technique of implanting the stentless porcine mitral valve.
AB  - The new stentless porcine mitral valve was developed to serve as an anatomically
      correct substitute for a diseased mitral valve. Extensive acute animal
      experimentation was performed, and from this the logical sequence for selecting
      the correct valve size and the specific technique for implanting it were
      determined. The following are the major steps to successfully implant a mitral
      stentless valve: First, mitral valve complex analysis must be done to determine
      the correct procedure to be performed and the feasibility of using the stentless
      mitral valve. Second, the correct size of stentless mitral valve must be chosen.
      Third, the papillary muscle anatomy must be assessed to determine the site and
      number of sutures necessary for securely holding the new origin of the new
      chordae. Fourth, the papillary muscle sutures must be anchored to the free
      pericardial edge of the new chordal origin. Fifth, the chordal alignment with
      both trigonal areas must be perfect. Sixth, the annulus may be sutured using
      either continuous or interrupted sutures. Perioperative echocardiography,
      preferably transesophageal echocardiography, should be done in every patient.
      Although reoperation was necessary in 5 patients (non-valve-related), the results
      in 74 patients (3 early and 3 late non-valve-related deaths excluded) followed up
      for at most 26 months (mean, 14 months) have been excellent. The quality of the
      results obtained in this initial clinical trial has reinforced our current
      preference for this valve in patients requiring mitral valve replacement. Longer
      follow-up is required to confirm that these good results continue.

PMID- 7646206
TI  - Mechanical versus biological valve prosthesis: a ten-year comparison regarding
      function and quality of life.
AB  - To determine the long-term outcome of biological and mechanical heart valve
      prostheses, we compared the Biocor, a new generation of porcine bioprosthesis,
      with the St. Jude Medical mechanical prosthesis. One hundred consecutive patients
      operated on between 1983 and 1985 with the Biocor in the aortic, mitral, or both
      positions (without concomitant cardiac procedures) were followed until January
      1993, together with 100 matched patients implanted with the St. Jude valve. The
      mean age was 66 and 67 years, respectively. The follow-up was 100% complete.
      Valve-related mortality differed significantly, with a freedom rate of 80.7% +/-
      9.0% for the St. Jude group and 97.7% +/- 1.6% for the Biocor group. There were
      few thromboembolic events, with no significant difference between the groups.
      Anticoagulant-related hemorrhage occurred almost exclusively in the St. Jude
      group (2.3%/patient-year), and reoperations were required almost exclusively in
      the Biocor group (1.8%/patient-year). The occurrence of all valve-related
      complications (mortality plus morbidity) differed markedly, with an actuarial
      freedom at 10 years of 55.8% +/- 9.8% for St. Jude and 80.0% +/- 4.4% for the
      Biocor. Quality of life and echocardiographic measurements did not differ
      significantly between the groups. We conclude from this study that the long-term
      performance of the Biocor and St. Jude are comparable, even though valve-related
      complications tended to be fewer in the Biocor group, with a significantly lower
      incidence of valve-related death.

PMID- 7646205
TI  - Bioprosthetic and mechanical valves in the elderly: benefits and risks.
AB  - There is controversy over whether elderly patients benefit from the durability of
      mechanical valves when balanced against the risk of anticoagulation. From 1976 to
      1993, 576 patients 65 years old or older underwent isolated valve replacement
      with mechanical (n = 250) or bioprosthetic valves (n = 326). Total follow-up was
      2,222 patient-years. Probability of survival and freedom from thromboembolism and
      prosthetic valve endocarditis were not different between the two groups. There
      was a significant difference (p = 0.015) in freedom from anticoagulant-related
      hemorrhage. Two patients with mechanical prostheses and 7 patients with
      bioprostheses were reoperated. However, actuarial freedom from reoperation was
      not different (p = 0.73) in both groups, with no hospital mortality, whereas
      mortality from thromboembolic events and anticoagulant-related hemorrhage was
      three times higher in patients with mechanical prostheses as compared with
      patients with bioprostheses (1.08% versus 0.36% per patient-year). The benefit
      from the durability of mechanical valves, compared with bioprostheses, is smaller
      than expected because of the limited number of patients exposed to the onset of
      bioprosthetic structural deterioration. Elderly patients without absolute
      indication for anticoagulation should preferentially receive bioprostheses for
      valvular replacement.

PMID- 7646207
TI  - Clinical performance of biological and mechanical prostheses.
AB  - Prosthetic valve replacement remains the most viable alternative for the
      treatment of severely diseased heart valves. The cumulative experience of
      mechanical protheses and bioprostheses was evaluated for a 10-year performance
      comparison: Carpentier-Edwards standard porcine bioprosthesis (CE-S), 1,214
      operations; Carpentier-Edwards supraannular porcine bioprosthesis (CE-SAV),
      2,489; and mechanical prostheses, 1,364 operations (St. Jude Medical,
      Carbomedics, Duromedics, and Bjork-Shiley Monostrut). The freedom from
      thromboembolism and hemorrhage at 10 years was 82% for CE-S, 78% for CE-SAV, and
      65% for mechanical prostheses (p < 0.05). The relationship existed for major
      thromboembolism and hemorrhage, 91% (CE-S), 87% (CE-SAV), and 88% (mechanical) (p
      < 0.05), without clinical relevance. The freedom from structural valve
      deterioration and valve-related reoperation favored mechanical prostheses (p <
      0.05) at 10 years (structural failure: 78% for CE-S, 81% for CE-SAV, and 99% for
      the mechanical group; reoperation: 74% for CE-S, 76% for CE-SAV, and 88% for
      mechanical prostheses). The freedom from fatal reoperation was not clinically
      different: 96% for CE-S, 99% for CE-SAV, and 99% for mechanical prostheses (p <
      0.05) at 10 years. The freedom from valve-related mortality was not different (p
      = not significant) at 10 years: 87% for CE-S; 92% for CE-SAV; and 91% for
      mechanical. The freedom from permanent impairment or residual morbidity,
      primarily from thromboembolism, was 95% for CE-S, 92% for CE-SAV, and 95% for
      mechanical group (p < 0.05) but not clinically relevant.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7646208
TI  - Comparison of porcine bioprostheses and mechanical prostheses in multiple valve
      replacement operations.
AB  - The performance of porcine bioprostheses and mechanical prostheses in multiple
      valve replacement operations was evaluated in 494 patients with 553 operations
      between 1975 and 1992. Porcine bioprostheses were implanted in 351 multiple
      replacement operations and 202 operations were performed with mechanical
      prostheses. The mean age of the bioprosthesis group was 59.1 +/- 14.4 years and
      of the mechanical prostheses group, 55.9 +/- 13.3 years. Concomitant procedures,
      primarily coronary artery bypass grafting, were performed in 27.4% (96 patients)
      of the bioprosthesis group and 20.8% (42 patients) of the mechanical prosthesis
      group (p = not significant [NS]). The early mortality for the bioprosthesis group
      (BP) was 12.0% (42 patients), whereas for the mechanical prosthesis (MP) group it
      was 10.9% (22 patients) with no difference (p = NS) for the performance with or
      without concomitant procedures, primarily coronary artery bypass grafting. The
      total cumulative follow-up was 1,914 years for BP and 458 years for MP group. The
      late mortality was different between the groups (p < 0.05), 6.1%/patient-year for
      BP and 3.7%/patient-year for MP. The difference in late mortality was not
      different (p = NS) for performance of concomitant procedures and not different (p
      = NS) for the absence of concomitant procedures, 5.6%/patient-year for BP and
      2.2%/patient-year for MP. The freedom from thromboembolism- and
      antithromboembolic-related hemorrhage favored the biological population (p <
      0.05) at 10 years with 79.7% +/- 3.4% for BP and 75.4% +/- 5.0% for MP. The
      freedom from structural valve deterioration was 100% for MP, whereas for the BP
      group, 94.7% +/- 1.6% at 5 years and 65.9% +/- 4.3% at 10 years.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7646209
TI  - Reoperation in biological and mechanical valve populations: fate of the
      reoperative patient.
AB  - From 1975 through 1992 inclusive, reoperative valve replacement (REOP) was
      required by 12.9% of patients (708/5,499). Of 1,355 patients with mechanical
      prostheses (MP), 46 (3.4%) came to REOP versus 662 of 4,144 patients (16%) with
      biological prostheses (BP). Early REOP mortality rate was 17.4% (8/46) for MP and
      10.6% (70/662) for BP (p = not significant). It was higher with age greater than
      75 years (p < 0.05) and trended higher with concomitant procedures and with
      increasing number of REOPs (p = not significant). The percentage freedom from
      REOP at 5 and 10 years for all BP was 96.0% +/- 0.4% and 74.9% +/- 1.1% compared
      with 93.6% +/- 1.2% and 87.9% +/- 2.5% for MP. The most common cause of REOP in
      the BP patients was structural valve deterioration, which was uncommon in
      patients with MP (72% versus 2% of REOP but only 15% versus 0.1% of initial
      implants). Nonstructural dysfunction was the leading cause of REOP in the MP
      group (65% versus 11%). Prosthetic valve endocarditis (18% versus 10%) and
      thromboembolic complications (10% versus 1%) were also more frequent causes of
      REOP in MP patients. However, the increased relative role of these factors with
      MP is due to the minimal incidence of structural valve deterioration. When
      related to the original choice of MP versus BP, only thromboembolic complication
      (3.8 times) was more prevalent as a cause of REOP in patients receiving MP at
      their previous procedure (p = not significant). For patients who previously
      received BP, structural valve deterioration (69 times) was more likely to lead to
      REOP than with MP (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7646210
TI  - Tricuspid valve replacement: porcine bioprostheses and mechanical prostheses.
AB  - The clinical performance of tricuspid valve replacement with bioprostheses and
      mechanical prostheses was assessed in a series of 5,489 total valve replacement
      operations performed from 1975 to 1992. There were 97 (1.8%) tricuspid valve
      replacements in 94 patients (16 men, 78 women) with a mean age of 55.4 +/- 13.8
      years. Bioprostheses (mean patient age, 55.9 +/- 14.1 years) were used in 83
      operations and mechanical prostheses (mean patient age, 52.1 +/- 11.9 years) were
      used in 14 operations. There were 30 isolated tricuspid valve replacements and 67
      tricuspid valve replacements incorporated in multiple valve replacements. The
      total cumulative follow-up was 360 patient-years (bioprostheses, 321 years;
      mechanical prostheses, 39 years) (96.8% complete). The mean follow-up was 3.7
      years (bioprostheses, 3.9 years; mechanical prostheses, 2.8 years) (p = not
      significant). The early mortality was 14.4% (bioprostheses, 14.5%; mechanical
      prostheses, 14.3%) (p = not significant) (isolated replacement, 13.3%; multiple
      replacement, 14.9%). The late mortality was 9.2% per patient-year (isolated
      replacement, 12.2% per patient-year; multiple replacement, 7.9% per patient
      year). The freedom from structural valve deterioration at 5 and 7 years was 100%
      for mechanical prostheses and 97.1% +/- 2.9% for bioprostheses (p = not
      significant). For isolated tricuspid valve replacement, the freedom from
      structural valve deterioration for bioprostheses was 90.9% +/- 8.7% at 5 years
      and at 7 years (p = not significant). For the mechanical prostheses, the freedom
      was 100%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7646211
TI  - Perioperative events in patients with failed mechanical and bioprosthetic valves.
AB  - From 1963 through 1991, 1037 patients underwent reoperative valvular procedures.
      The 478 patients having reoperations for either failed bioprosthetic (n = 212) or
      mechanical (n = 266) valves were evaluated. There were 210 male (44%) and 268
      female (56%) patients. The mean age at reoperation of the patients in the
      bioprosthesis group was 59.7 years and and that in the mechanical valve group was
      56.1 years (p = 0.0006). The mean interval to the time of reoperation was 84.7
      months in the mechanical valve group and 74 months in the bioprosthesis group.
      There was no difference between the two groups in the functional class at
      reoperation. More severe mitral valve stenosis and incompetence, more severe
      aortic valve stenosis, and higher right ventricular and pulmonary arterial
      pressures were noted in the bioprosthesis group than in the mechanical valve
      group. Hemolysis (p = 0.05) was more prevalent in the patients with mechanical
      valves than in the ones with bioprostheses. A longer aortic occlusion time (p =
      0.0001) and longer cardiopulmonary bypass time (p = 0.0001) were required for the
      reoperations in the bioprosthesis group. The operative mortality was 13.2% for
      the bioprosthesis patients and 12.4% for the mechanical valve patients. The risk
      factors for hospital death included the cross-clamp time (p = 0.0001), the
      functional class (p = 0.00001), the presence of ascites (p = 0.02), hepatomegaly
      (p = 0.002), and decreasing ejection fraction (p = 0.05). We conclude that
      mechanical valve failures do not produce catastrophic events resulting in poor
      reoperative results.

PMID- 7646212
TI  - Proceedings of the VI International Symposium for Cardiac Bioprostheses.
      Vancouver, British Columbia, Canada, July 29-31, 1994.

PMID- 7646213
TI  - Allograft aortic valve replacement: long-term follow-up.
AB  - Aortic valve replacement using an allograft aortic valve has been performed on
      804 patients. From December 1969 to May 1975, 124 patients received a nonviable
      allograft valve sterilized by incubation with low-dose antibiotics and stored for
      weeks by refrigeration at 4 degrees C (series 1). From June 1975 to January 1994,
      680 patients received viable allograft valves, now cryopreserved early within 2
      hours of collection from transplant recipient donors, 6 hours for multiorgan
      donor valves and 23 hours (mean) for autopsy valves from donor death. The 30-day
      mortality was 8.9% +/- 5% (95% confidence limits) for series I and 2.8% +/- 1%
      (95% confidence limits) for series II. Actuarial patient survival including
      hospital mortality at 15 years was 56% +/- 5% for series I and 62% +/- 5% for
      series II. The probability of a thromboembolic event was low, freedom at 15 years
      being 95% +/- 1% for patients receiving allografts with or without associated
      coronary bypass procedures and 81% +/- 5% for patients having allografts with
      other associated procedures (eg, mitral valve operations). Actuarial freedom from
      endocarditis was similar for the two series, 91% +/- 3% (series I) and 94% +/- 2%
      (series II) at 15 years. The freedom from valve incompetence, from reoperation
      for all causes, and from structural deterioration demonstrated clearly the
      inferiority of the 4 degrees C stored allograft valves. For structural
      deterioration as identified clinically, at reoperation and at death, freedom from
      this event at 15 years was 45% +/- 6% for series I and 80% +/- 5% for series II
      (p value for the difference is 0).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7646214
TI  - Accelerated degeneration of allografts in the first two years of life.
AB  - Between January 1988 and May 1994, 53 of 159 patients have received cryopreserved
      aortic and pulmonary allografts for reconstruction of the pulmonary circuit in
      the first 2 years of life with body weight ranging from 2.2 to 18 kg (mean, 8.2
      +/- 3.4 kg). The implanted allografts ranged in internal diameter from 9 to 23 mm
      (mean, 16.3 +/- 3.5 mm). Of the 38 survivors who regularly had postoperative
      echocardiographic examinations 15 (39.5%) underwent cardiac catheterization 1 to
      31 months after operation. Allograft dysfunction (gradient > or = 50 mm Hg with
      or without pulmonary insufficiency) was confirmed in 9 patients leading to
      reoperation in 5 and valvulo-angioplasty in 4. At 48 months actuarial survival
      was 64%. In the aortic and pulmonary allografts freedom from wall calcification
      at 20 months was 19% and 100%, respectively. Freedom from valve dysfunction in
      patients with aortic and pulmonary allografts was 53% and 88%, respectively; it
      was 49% in allografts with an internal diameter of 17 mm or smaller. Freedom from
      reoperation in all patients was 78%. In conclusion, young age, antigenicity (ABO
      compatibility), and type of allograft seemed to be independent risk factors for
      early allograft conduit degeneration and late valve dysfunction. Pulmonary
      allografts seemed to be more resistant to early wall calcification and valve
      dysfunction than aortic allografts.

PMID- 7646215
TI  - Aortic valve replacement with allograft/autograft: subcoronary versus
      intraluminal cylinder or root.
AB  - From April 1990 to May 1994, 89 patients (median age, 42 years; range, 10 days to
      66 years) underwent aortic valve or root replacement with allografts or
      autografts. Thirteen patients were less than 18 years old at the time of
      operation. Indication for aortic valve replacement was aortic stenosis (50
      patients, 56%), small stenotic prosthesis (2 patients, 2%), aortic valve
      endocarditis (19 patients, 21%), isolated aortic regurgitation (17 patients,
      19%), and type II truncus arteriosus (1 patient, 1%). The subcoronary
      implantation was used in 45 patients (group A), and implantation of an
      intraluminal cylinder (16 patients) or complete root replacement (28 patients)
      was performed in the remaining 44 patients (group B). The Ross procedure was
      performed in 22 patients. Intraoperative transesophageal echocardiography was
      used routinely. Five patients died in the early postoperative period (6%), 2 in
      group A and 3 in group B. Three other patients required immediate replacement of
      a failing graft by a mechanical prosthesis (1 in group A and 2 in group B). There
      has been no late death. All survivors remained in New York Heart Association
      functional class I and were free of thromboembolic complications. Endocarditis
      occurred in 2 patients, 1 year after operation. Both were successfully treated
      medically. Echocardiographic studies were obtained serially in every patient.
      Four patients, 2 in group A and 2 in group B underwent reoperation because of
      mild-to-moderate aortic regurgitation (rate of reoperation, 5%). Two valves were
      repaired and two were replaced by an allograft.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7646216
TI  - Subcoronary implantation or aortic root replacement for human tissue valves:
      sufficient data to prefer either technique?
AB  - The aortic root replacement technique with aortic allograft or pulmonary
      autograft might be superior to the subcoronary allograft implantation technique
      with regard to aortic regurgitation. We explored the influence of the learning
      process on the incidence of reoperation and the severity of postoperative aortic
      regurgitation as assessed by color Doppler echocardiography. The subcoronary
      implantation technique was used in 81 patients, and root replacement was done in
      63 patients. The first 30 patients of each group were considered as the surgeons'
      learning curve. Reoperations were more common in the subcoronary implantation
      group. After exclusion of early reoperations, the median regurgitation score
      based on echocardiographic examination was 0.22 in the first 30 patients from the
      subcoronary implantation group and 0.14 in the root replacement group. The
      subsequent patients from these groups had regurgitation scores of 0.20 and 0.17,
      respectively. Statistical analysis of these data showed no significant
      difference. This interim report suggests that the learning curve for the surgical
      procedure and the grouping of echocardiographic data influence the interpretation
      of follow-up studies. The superiority of either technique with regard to aortic
      regurgitation has yet to be proved.

PMID- 7646217
TI  - Root replacement for all allograft aortic valves: preferred technique or too
      radical?
AB  - From November 1985 to January 1994, 146 patients have received a viable
      cryopreserved allograft for aortic root replacement. The follow-up was complete,
      with all events included to March 1st, 1994. The median age of patients was 49
      years; 83.6% were male. Valve dysfunction (91 patients), primary aortic wall
      disease (45 patients), and a combination of both (10 patients) were the
      indications for aortic root replacement. The current operative mortality is 1.7%
      (three deaths in 172 patients to July 1st, 1994). Four late deaths have occurred,
      with an 8-year actuarial survival of 85% +/- 8% (95% confidence limits).
      Endocarditis (two events) and thromboembolism (four events) had a low incidence.
      Structural deterioration (three events) and reoperation for all causes (nine
      events) have constituted low morbidity and are compared with the results after
      non-root allograft implantation techniques. The clinical and echocardiographic
      evidence indicates that the immediate results of valve function with root
      replacement are superior. But no statistical difference between aortic root
      replacement and non-root procedures is apparent at 8 years, indicating that a
      longer follow-up is required before the answer to the question "preferred
      technique or too radical" can be answered.

PMID- 7646219
TI  - Reoperative aortic valve operation after homograft root replacement: surgical
      options and results.
AB  - The surgical options available and the associated operative risks for repeat
      aortic valve replacement after free-standing homograft root replacement with
      reimplantation of the coronary arteries are as yet undefined. We therefore
      reviewed our experience with repeat aortic valve replacement between January 1976
      and July 1994 and identified 22 such procedures performed on 21 patients after
      homograft or autograft root replacement. Reoperation was indicated for structural
      deterioration in 16 and for bacterial endocarditis in 6 patients. Associated
      procedures were undertaken in 5 patients, and 4 procedures were performed
      emergently. Significant calcification of the homograft wall was noted in over
      half of all patients. There were no coronary ostial complications. In 13 patients
      new valves were inserted within the previous root: 9 mechanical valves and 4
      subcoronary homografts. In 9 patients the root was re-replaced. The mean cross
      clamp time was 85 (+/- 20) minutes and mean cardiopulmonary bypass time was 123
      (+/- 32) minutes. There were no early deaths and 5 late deaths. Two patients
      required reoperation for bleeding and 2 experienced low cardiac output syndromes
      postoperatively. Univariate analysis failed to identify any variables predictive
      of outcome. We conclude that repeat aortic valve replacement after homograft root
      replacement, even in the presence of significant calcification, can be undertaken
      with an acceptable operative risk and should not be delayed until irreversible
      ventricular dysfunction has occurred. The same options available at initial valve
      replacement may be employed at reoperation, although extensive calcification
      mandates repeat root replacement.

PMID- 7646220
TI  - [Criminal aspects of child abuse].

PMID- 7646218
TI  - Allograft aortic root replacement: standardization and simplification of
      technique.
AB  - A variety of surgical techniques for implantation of an allograft aortic valve
      have been described. Compounding this confusion, the host pathologic processes
      necessitating aortic valve or root replacement are many, often associated with
      asymmetry of the aortic root and valve annulus. These complexities can now be
      negated by routinely performing allograft aortic root replacement with pedicle
      coronary artery reimplantation in all situations. This procedure is described in
      a simple step-by-step manner that makes it amenable to all cardiac surgeons
      independent of experience.

PMID- 7646221
TI  - [Cause of death in a patient lifting device].
AB  - Under the aspect of unusual and primarily obscure finding situations of dead
      bodies the case of a 81-year-old female occupant of an old people's home is
      reported. The woman was found dead being suspended by the hook of a patient's
      lifting machine, which had perforated through the floor of the mouth into the
      oral cavity. In the course of judicial inquiry first a homicide or a suicide,
      respectively, were justly considered. The autopsy results and circumstances of
      the case, however, pointed to a natural death (acute coronary insufficiency) with
      a preterminal/agonal fall into the hook of the lifting machine. An orthostatic
      circulatory dysregulation due to the suspension has possibly functioned as an
      additional mechanism accelerating death.

PMID- 7646222
TI  - [2 suicides with self-fabricated gunshot devices: technical forensic and
      morphologic ballistic characteristics].
AB  - Two suicides with home-made guns firing conventional ammunition are reported.
      Three different classes of homemade guns can be distinguished. Special
      characteristics of the interior and exterior ballistics of the home-made guns
      caused unusual muzzle imprints, intensive soot deposits at the entrance wounds
      and on the hands, intensive CO-effects, burns and in one case a skin laceration
      of the hand holding the weapon. The bullets showed a reduced penetration depth,
      characteristic firing marks were missing.

PMID- 7646223
TI  - [Suicide with a nail gun device: wound ballistics and wound entry morphology].
AB  - A man committed suicide by a contact shot to the left chest from a nail-gun. The
      nail caused a slit-like entrance wound and a penetrating heart injury. The front
      side of the nailgun led to an outer "muzzle imprint", the muzzle and the nail to
      an inner "muzzle imprint". Wound ballistics of nails are discussed.

PMID- 7646224
TI  - [Forensic medicine aspects of sudden death in sports].
AB  - Our study which deals with cases examined by the Institute of Forensic Medicine
      at the University of Geneva, of sudden nontraumatic death while engaged in
      sporting activities, covers the last fifteen years from 1980 to 1994. We
      discovered 31 cases, all males, aged between 17 and 68 years. There were 15 cases
      of young sportsmen (under the age of 45-50) where the cause of death was unclear,
      and where an autopsy was requested by the police and 16 cases, where we were
      asked to make an external examination of the bodies, in order to exclude any
      signs of violence. Of the 15 autopsies, 10 sportsmen presented signs of
      myocardial infarction and 2 showed evidence of hemorrhage in an atheromatous
      plaque. Five cases showed evidence of previous myocardial infarctions. The
      youngest victim was a 17-year-old boy with previously diagnosed obstructive
      cardiomyopathy.

PMID- 7646226
TI  - [Clarification of a break-in theft crime by multiplex PCR analysis of cigarette
      butts].
AB  - This paper describes the first use of multiplex PCR amplification kits for the
      analysis of DNA extracted from cigarette butts in a criminal case. Two suspects
      could be excluded as potential contributors to the samples, whereas the multi
      locus PCR-based DNa profile derived from the cigarette butts was consistent with
      a DNA profile derived from a third suspect. For identity testing in criminal
      cases where cigarette butts are involved, commercially available PCR
      amplification kits provide currently the most powerful tool. Furthermore this PCR
      based analysis can be implemented into most application orientated laboratories.

PMID- 7646225
TI  - [Errors in treatment of soft tissue phlegmon : expert assessment and forensic
      evaluation].
AB  - In ten cases of soft part phlegmons resulting in death (8) and amputation (2)
      respectively, various types of medical malpractice were evident. The diagnosis
      was missed, or the disease was correctly diagnosed but underestimated. Typical
      therapeutic mistakes were the omission of bacteriological investigations and of
      the proper antibiotical therapy, a delayed hospital admission, or a delayed or
      insufficient surgical intervention. These errors however could never be proved to
      have caused the unfavorable outcome in view of the doubtful prognosis of soft
      part phlegmons even under proper treatment. Thus, evident malpractice never
      resulted in a condemnation for bodily injury or involuntary manslaughter.

PMID- 7646227
TI  - [Questions concerning major clinical trials].

PMID- 7646228
TI  - [Immediate results of coronary endoprosthesis in threatening or occlusive
      dissections complicating angioplasty; the Geneva experience].
AB  - Between April 1988 and September 1993, 123 patients (average age 60.4 +/- 8.9
      years) underwent coronary stenting for threatening or occlusive dissection
      complicating angioplasty. The anterograde coronary flow was disturbed in 51% of
      cases (TIMI-0-2). The artery concerned was the left anterior descending in 59% of
      cases, the right coronary in 28% of cases, the circumflex in 12% and a coronary
      bypass graft in 1% of cases. Technically, the stenting was successful in 118
      cases (98%) and, in 21 cases, complete stenting of the dissection required the
      insertion of several stents. The minimal coronary diameter after expansion of the
      stent was 3.1 +/- 0.6 mm. During hospital follow-up, 3 deaths (3%) and 7 Q-wave
      infarcts were observed. Twenty-eight patients (23%) developed a haemorrhagic
      complication, including 2 retroperitoneal and 2 intracerebral bleeds. Eight
      patients (6%) underwent coronary bypass grafting, as an emergency in 4 cases and
      semi-electively in another 4 cases. One hundred and five patients (89%) survived
      the intra-hospital period without major complications (death, Q-wave infarction,
      emergency coronary bypass surgery or severe haemorrhage). Coronary stenting for
      threatening or occlusive dissection complicating angioplasty seems to be a
      reasonable solution and a usually definitive one. The frequency of haemorrhagic
      complications underlines the need for strict clinical and biological
      surveillance.

PMID- 7646229
TI  - [Frequency of angiographic restenosis after 6 months and long-term outcome of
      coronary angioplasty].
AB  - Five hundred patients with a mean age of 59 years were followed up for an average
      of 32 months after coronary angioplasty. All patients were included in a
      prospective study comprising coronary angiography at 6 months for 379 patients
      (91% primary successes). The long-term outcome was evaluated by a questionnaire
      or telephone interview in all cases. The global primary success rate was 84.4% in
      this series. The primary failures include 1.8 fatalities, 0.6% myocardial
      infarction, 2% emergency coronary bypass surgery and 11.2% without immediate
      clinical consequences. At 6 months, there were 48% of restenoses (182/379
      patients) and 28% underwent immediate repeat angioplasty (141/500 patients) with
      a primary success rate of 91%. After the repeat angioplasty, the restenosis rate
      was 43% but this varied according to the time from the first restenosis: 60% when
      the interval was short (under 2 months) compared with 21% when the interval was 6
      months (p < 0.01). The actuarial survival rates at 4 years were 95% after
      successful angioplasty 96% after uncomplicated failures or medically treated
      restenosis and 98% after bypass surgery. The predictive factors for secondary
      death were age of over 70 years, previous non-thrombolized myocardial infarction
      and complications of angioplasty. The long-term outcome was good despite the 48%
      6 months restenosis rate requiring revascularisation procedure in 73% of cases.

PMID- 7646230
TI  - [Coronary artery surgery after 70 years: an analysis of the risk factors of
      operative mortality].
AB  - The risk factors of operative mortality after coronary bypass surgery in patients
      over 70 years of age were studied in a consecutive series of 109 patients
      operated in our department between January 1990 and June 1992. The anginal pain
      was classified stage III or IV in 92 cases. Seventy-nine patients had triple
      vessel disease, 36 patients had left main stem stenosis and 57 had previous
      myocardial infarction. Twenty-six patients had ejection fractions of less than
      50% and 6 were less than 30%. The average number of bypass grafts was 2.35.
      Associated procedures included 9 endarteriectomies of the left main coronary, one
      endarteriectomy of the left anterior descending and right coronary arteries, 2
      myotomies involving the left anterior descending artery, 3 ventricular remodeling
      procedures and 3 carotid endarteriectomies. Non-lethal postoperative
      complications were mainly pulmonary infections (19 cases). The operative
      mortality was 5.1% in the group with stable angina. On the other hand, the
      mortality was 31.2% in the group with unstable angina operated as an emergency or
      semi-emergency. The causes of death were mainly postoperative low output states
      (16 cases) and polyarteriopathy (mesenteric infarction: 6 cases). Although age
      was related to operative risk, the main prognostic factor was the preoperative
      cardiovascular status. The degree of emergency, unstable angina, left main
      coronary disease, duration of cardio-pulmonary bypass and the necessity for
      inotropic or mechanical support in the postoperative phase were significant risk
      factors for death. Sex, cardiovascular risk factors, previous myocardial
      infarction and duration of aortic clamping were not correlated to
      mortality.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7646231
TI  - [Prognosis of non-revascularized triple coronary vessel disease. Apropos of 87
      cases].
AB  - Between 1982 and 1988, 87 patients (74 men, 13 women), with an average age of
      59.6 +/- 10.1 years, had triple coronary artery disease and did not undergo any
      medical or surgical revascularisation, mainly because of the severity of the
      coronary disease or left ventricular dysfunction. Sixty-four patients had
      previous myocardial infarction, 33 unstable angina and 37 left ventricular
      failure. At coronary angiography, 31 patients had Class III or IV (NYHA) angina.
      The cardiothoracic ratio was 0.50 +/- 0.06; the left ventricular ejection
      fraction was 0.47 +/- 0.20. During follow-up of 3.9 +/- 2.6 years (2 patients
      lost to follow-up), 35 patients died (26 of cardiac and 9 of non-cardiac causes),
      giving a 5 year actuarial survival of 63%. In univariate analysis, the factors
      predictive of increased cardiac mortality were: absence of alcohol consumption (p
      = 0.013); class 3 or 4 angina (p = 0.017); resting angina (p = 0.030); cardiac
      failure (p = 0.0006); chest X ray showing interstitial or alveolar oedema (p =
      0.002); increased cardiothoracic ratio (p = 0.003). A decreased left ventricular
      ejection fraction was only at the limit of statistical significance (p = 0.054).
      In multivariate analysis (Cox model), only 4 variables were correlated with
      increased cardiovascular mortality: resting angina (relative risk, RR = 2.56),
      cardiac failure (RR = 2.55), increased cardiothoracic ratio (RR = 2.14), absence
      of alcohol consumption (RR = 4.43). These results confirm the poor prognosis of
      patients with triple vessel disease not revascularised. They show the value of
      clinical appreciation to determine the prognosis of these patients.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7646233
TI  - [Results of endoprostheses in the iliac arteries; an experience apropos of 47
      implantations].
AB  - Obstruction or stenosis of the iliac artery was treated by placement of an
      endoprothesis in 41 patients. A total of 47 lesions was treated. 26 patients had
      poor results of balloon angioplasty including residual stenosis (7 cases),
      restenosis post angioplasty (7 cases), and dissection (12 cases). 15 patients had
      iliac occlusion. The endoprothesis used was a self expandable flexible
      endoprothesis (Wallstent) in 26 cases and a balloon expandable flexible
      endoprothesis (Strecker) in 21 cases. Complications included one thrombosis of
      the endoprothesis occurred immediately after placement, one hematoma. No distal
      embolization occurred. Patency at the end of the study was 70% at 9 months and
      50% at 21 months. Patency was better with the Wallstent endoprothesis (60% at 21
      months) than with the Strecker endoprothesis (38% at 21 months). Results was
      better with lesions of the common iliac artery, and when the indication was
      dissection or failure of angioplasty. During the 21 months of follow-up 18
      occlusions or restenosis occurred. At the end of the study 20 patients (49%) were
      asymptomatic and improvement was achieved in 9 (22%), the clinical success rate
      was 71%. One amputation was required.

PMID- 7646234
TI  - [Limitations of ventricular late potentials in atrial fibrillation].
AB  - It is generally admitted that the chaotic atrial activation in atrial
      fibrillation makes analysis of ventricular late potentials uninterpretable.
      However, some workers have contradicted this affirmation. The authors performed
      signal averaged electrocardiogram in 17 patients with atrial fibrillation before
      cardioversion for external D.C. shock. The recording was repeated 15 minutes
      after restoration of sinus rhythm. None of the patients had complete bundle
      branch block in atrial fibrillation or sinus rhythm. Analysis was made with a
      band pass filter of 40 Hz and to a final noise level of 0.3 microV. The
      positivity of late ventricular potentials was confirmed by the presence of at
      least 2 of the usual 3 criteria: an averaged QRS duration > 120 ms, a RMS 40 < 20
      microV and a LAS > 40 ms. The mean duration of the averaged filtered QRS complex
      was 122 ms in atrial fibrillation and 112 ms in sinus rhythm, a non significant
      decrease of 9%. The mean value of the RMS 40 was 24 microV before cardioversion
      versus 29 microV after restoration of sinus rhythm, a significant increase of 19%
      (p < 0.05). Finally, the mean duration of the LAS in atrial fibrillation was 45
      ms, decreasing to 35 ms in sinus rhythm, a significant reduction of 22% (p <
      0.05). In atrial fibrillation, 10 patients had ventricular late potentials (2
      positive criteria) and 7 had no ventricular late potentials. In sinus rhythm, on
      the other hand, 6 patients were positive and 11 negative.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7646232
TI  - [Vaso-reactive properties of radial and internal mammary arteries: application to
      coronary bypass surgery].
AB  - Satisfactory results were obtained with the radial artery used as a conduit for
      coronary artery bypass. However, spasm of this conduit was observed. Human radial
      and internal mammary artery ring segments were studied in organ chambers.
      Potassium chloride, norepinephrine, serotonin and thromboxane A2 mimetic were
      used to obtain dose-response curves, permitting assessment of force of
      contraction and sensitivity. The radial artery presents stronger contractions
      than the internal mammary artery. The two vessels have equal sensitivity to the
      vasoconstrictors used. These data emphasize the hyperreactivity of the radial
      artery and the need for prevention of vasospasm when this vessel is used as a
      conduit for coronary artery bypass.

PMID- 7646235
TI  - [Heart rate variability in chronic cardiac failure insufficiency. Effect of
      severity and etiology].
AB  - The variability of the heart rate is a sign of the activation of the autonomic
      nervous system. This parameter was studied in 21 control subjects and 72 patients
      with chronic cardiac failure (20 stage II, 37 stage III and 15 stage IV of the
      NYHA) due to ischaemic heart disease in 48 cases and idiopathic in 24 cases.
      Spectral and non-spectral analysis of the variability of the heart rate recorded
      during 24 hour Holter monitoring was performed with the Marquette Electronics
      8000 software. Plasma noradrenaline was measured in whole blood by HPLC. The left
      ventricular ejection fraction was measured by echocardiography. There was a
      superior to 40% decrease in non-spectral and over 50% decrease in spectral
      parameters in patients with cardiac failure. This was more pronounced when the
      cardiac failure was in an advanced stage. The decrease in sinus rhythm
      variability was proportional to the functional class (SDANN stage II: 96 +/- 34
      ms; stage III: 63 +/- 34 ms; stage IV: 54 +/- 33 ms). Moreover, the non-spectral
      parameters were correlated to the ejection fraction and plasma noradrenaline
      levels (p < 0.01). In addition, with the same NYHA stage, plasma noradrenaline
      concentration, ejection fraction and heart rate, the SDNN and the pNN50 were over
      50% lower in idiopathic cardiomyopathy than in ischaemic cardiomyopathy. In
      conclusion, the variability of the heart rate is reduced in chronic cardiac
      failure in relation with the severity and aetiology of the underlying disease.

PMID- 7646236
TI  - [Recommendations for good practice of intracavitary techniques for diagnosis and
      treatment of cardiac arrhythmia. Diagnostic electrophysiology; interventional
      electrophysiology; permanent cardiac stimulation; implantable automatic
      defibrillators].

PMID- 7646237
TI  - [Left main coronary artery disease].
AB  - There are many causes of left main coronary artery disease, the first of which is
      atherosclerosis. Other rarer causes may be observed, such as acute and chronic
      occlusions, spasm and primary and secondary dissection. The prevalence of
      stenosis of the left main coronary artery at coronary angiography is about 5%.
      The risk factors are the same as for coronary artery disease. The symptoms are
      angina, especially unstable angina. The diagnosis is suspected on the finding of
      an extremely positive exercise stress test, confirmed by coronary angiography.
      The results of the prospective large scale Veterans Administration trial showed
      surgery to be the treatment of choice with a 30 months survival of 80% in the
      surgical group compared with 64% in the medical group. The operative morbidity
      and mortality is less than 10% at present. Recent studies have reported a medium
      term mortality of 4.3 to 10.25% with follow-up periods of 24 and 43 months
      respectively. The long-term survival and functional improvement are excellent,
      with values of nearly 80%. Chronic occlusion of the left main stem is rare, 0.01
      to 0.7% in coronary angiographic studies. There is no difference in presentation,
      electrocardiographic or stress test features compared with other severe coronary
      artery disease. The diagnosis is angiographic and the treatment surgical because
      of the mediocre natural history with risks of sudden death and severe infarction.
      Acute occlusion of the left main coronary is rare for generally fatal. The
      mechanism is acute thrombosis and the clinical presentation is that of extensive
      infarction usually with cardiogenic shock.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7646239
TI  - [Recanalization of chronic occlusions and myocardial infarction occurring during
      reocclusion. Apropos of 2 cases].
AB  - Although recent techniques have significantly improved the frequency of
      disobliteration of chronic occlusions, the potential complications in terms of
      mortality, emergency bypass surgery and myocardial infarction seem as common as
      in angioplasty of stenosis. Of these complications, the occurrence of infarction
      during reocclusion at the site of angioplasty has not been described and even
      been refuted by some authors. We report two cases of acute infarction, one of
      which was transmural, occurring during late reocclusion after disobliteration of
      a chronically occluded artery.

PMID- 7646238
TI  - [Atypical coarctation of the thoracic aorta caused by fibromuscular dysplasia].
AB  - Fibromuscular dysplasia is a non-inflammatory disease unrelated to
      atherosclerosis of the small and medium sized arterial walls, which often affects
      the renal and carotid arteries and occurs mainly in women. The authors report a
      case of atypical coarctation of the thoracic aorta due to fibromuscular dysplasia
      confirmed histologically in a 27 year old man. Arteriography was performed
      because of hypertension and asymmetry of blood pressure measurements and showed
      irregular stenosis of the aortic isthmus and of the origin of the left subclavian
      artery. Surgery comprised resection of the pathological segment of the aorta
      which was replaced by a prosthetic tube with reimplantation of the left
      subclavian artery. Histological examination showed fibromuscular dysplasia in
      perimedial areas and diffusely throughout the media. To the author's knowledge
      this is the first case to be reported in the medical literature.

PMID- 7646240
TI  - [Arrhythmia and conduction defects in polymyositis].
AB  - The prevalence of cardiac complications of dermatomyositis and polymyositis is
      generally underestimated. The authors report the case of heart block as the
      presenting symptom of the disease, situated in the atrioventricular node.
      Initially paroxysmal, it eventually became permanent. It was associated with
      atrial (fibrillation and flutter) and ventricular hyperexcitability (ventricular
      tachycardia in runs). Myocardial biopsy provided histological proof of the
      cardiac disease and the definitive link between the nodal conduction defect and
      the polymyositis.

PMID- 7646241
TI  - [Myocardial revascularization using Vineberg's procedure; 23 years follow-up].
AB  - The authors report the case of a patient followed up for 23 years after a double
      myocardial implantation of the internal mammary arteries (Vineberg technique) for
      unstable angina. The result of this procedure of surgical revascularisation has
      been very satisfactory to date. The authors believe this to be the longest follow
      up reported in the medical literature.

PMID- 7646242
TI  - [Henri Warembourg (1905-1993)].

PMID- 7646243
TI  - [Left auricular myxoma and myocardial infarction].
AB  - The authors report the case of a 40 year old man with a postero-inferior
      myocardial infarction. Echocardiography showed a large left atrial myxoma.
      Coronary angiography performed 20 days after the onset of infarction was
      completely normal. The tumour was successfully removed surgically. The authors
      review the literature of this rare association (20 reported cases) which were
      commonly observed since the widespread use of echocardiography and coronary
      angiography. These investigations have improved the understanding of the
      physiopathology of this association. One of the possible hypotheses of diastolic
      mitral obstruction by the tumour was the probable mechanism of infarction in this
      case due to prolonged impaired coronary filling due to low cardiac output.

PMID- 7646244
TI  - [Coronary restenosis: the cardiologist facing problems of definitions].
AB  - Many angiographic definitions have been proposed to define restenosis after
      coronary angioplasty. The utility of each remains poorly defined. The aims of
      this study were: a) to analyse groups of patients defined by each of three
      criteria: > 50% stenosis (definition 1), loss > or = 50% of initial gain in
      diameter (definition 2), loss > or = 0.52 mm of minimal luminal diameter based on
      the variability of the angiographic measurement (definition 3) and, b) to compare
      the immediate attitude of the interventional cardiologist with the deferred
      quantitative angiographic analysis. The angiographic follow-up included 89
      patients. The angiographic restenosis rate was 37% (definition 1), 48%
      (definition 2) and 43% (definition 3). Restenosis as defined by criterion 1 was
      associated with the greatest degree of postangioplasty residual stenosis (p =
      0.02) whereas, with criteria 2 and 3, it was associated with less severe residual
      stenosis (p = 0.03 and p = 0.007). Definition 2 and 3 are the most similar and
      definitions 1 and 3 the most complementary. The sensitivity, specificity positive
      and negative predictive values for recurrence of angina with respect to
      angiographic restenosis (definition 1) were respectively 63.6%, 77.8%, 63.6%, and
      77.8% and are not significantly improved by associated analysis of exercise
      testing. Discordances between the decision of the interventional cardiologist and
      the results of quantitative angiography (definition 1) were noted in 12.4% of the
      stenosis studied, there measuring 44 to 64%. The judgement of the cathetiser of
      these intermediary stenoses was essentially influenced by the recurrence of
      angina during follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7646245
TI  - [Initial arterial pressure and prognosis of cerebrovascular accidents].
AB  - The present study analysed the charts of the patients admitted for acute stroke
      and assessed the relation between stroke mortality and initial blood pressure. Of
      the 388 patients admitted, 169 (44%) died. Mortality increased with advancing age
      and was higher in women, in hemorrhagic stroke (61%), and in patients with severe
      neurological deficit on admission. Average blood pressure on admission did not
      differ between the patients who died and those who survived. However, mortality
      was 42, 32, 57 and 62% in patients whose admission systolic blood pressure was,
      respectively, less than 160 mmHg, 160 to 199 mmHg, 200 to 249 mmHg and 250 mmHg
      or more. It described a similar curve when four categories of admission diastolic
      blood pressure were constituted. The data indicate a high case fatality rate in
      stroke patients. Mortality was higher in women; it increased with age and severe
      neurological deficit. The relation of stroke mortality to admission blood
      pressure suggests that it is not the lowest in patients with the lowest blood
      pressure, but in those with blood pressure level allowing the best brain
      perfusion after the onset of stroke.

PMID- 7646246
TI  - [Severe arrhythmia in the elderly: a prospective hospital study].
AB  - The prevalence of arrhythmia increases with age. Considered as an "ordinary"
      event in elderly patients, these arrhythmias may nevertheless have serious
      consequences. This study was undertaken to determine the clinical, aetiological
      and prognostic features of serious arrhythmias in a population of elderly
      subjects (> or = 70 years) hospitalised over a 20 months period and comprising
      202 patients (103 women, 99 men, mean age 79.6 +/- 5.9 years). Supraventricular
      arrhythmias are the most common by far (84.2%): 51.4% of patients had atrial
      fibrillation, 15.3% had atrial flutter; 12.9% had focal atrial tachycardia, 4.5%
      had junctional tachycardia. Of the ventricular arrhythmias (15.8%), there were 12
      sustained ventricular tachycardias, 4 torsades de pointes and 1 ventricular
      fibrillation. The increased duration of hospital stay (10 +/- 6 days on average)
      is related not to age but to the type of arrhythmia (longer for ventricular
      arrhythmias) and to left ventricular dysfunction. The main complications of
      arrhythmias were cardiac failure (52.4%), neurological deficits (37.4%) and
      angina (18.6%). Electrocardiographic signs of atrioventricular block were present
      in 62% of cases and QRS changes in 47.3% of cases. Ventricular arrhythmias were
      more commonly associated with intraventricular conduction defects, signs of
      myocardial necrosis and prolongation of the QT interval; they were also common in
      patients with left ventricular dysfunction and when the left ventricle was
      dilated. The aetiology of ventricular arrhythmias was mainly iatrogenic (50%) and
      ischaemic (21.8%), whereas the aetiologies of the supraventricular arrhythmias
      were varied, 14.7% of cases being idiopathic. Conversion to stable sinus rhythm
      was obtained in half the patients. A pacemaker was implanted in 10.8% of cases.
      The hospital mortality was 4.9%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7646247
TI  - [Repeated heart valve replacements: prognosis and results].
AB  - In order to determine the prognosis of reoperation for valvular replacement, we
      reviewed the results of a consecutive series of 124 patients operated in the
      department between 1974 and 1992 (163 multi redo operations). There were 69 women
      and 55 men, with a mean age 48 years; 77% of the patients were in functional
      class III or IV. Operations were performed as an emergency in 30% of cases.
      Endocarditis was found in 24% of cases and was an important risk factor in this
      content. The main indications for reoperation were periprosthetic leakage in
      28.8% of cases and failure of bioprostheses in 23.7%. The valvular replacement
      was simple in 61%, double in 32% and triple in 7% of cases. An associated
      procedure was necessary in 27% of cases. Mechanical devices were implanted in
      62.3% of cases. Peroperative mortality was 3% and hospital mortality, mainly from
      cardiac causes, was 21.7% for the second, 20% for the third and 55.6% for the
      fourth reoperations. Operative mortality was dependent on the number or
      reoperations, functional class, emergency surgery, duration of bypass and cross
      clamping time. Four per cent of patients were lost to follow-up and 30 patients
      died secondarily. The actuarial survival rate was 52% at 5 years and 33% at 10
      years, actuarial survival rate without valvular complication was 41% at 5 years
      and 19% at 10 years but the functional results remained good with over 90% of
      patients in functional class I or II at the end of follow-up.

PMID- 7646248
TI  - [Cardiac surgery in chronic hemodialysed patients: immediate and long-term
      results].
AB  - Between 1979 and 1993, 50 patients (33 men and 17 women) receiving chronic
      haemodialysis, underwent 53 cardiac surgical procedures in the department. The
      mean age was 56 +/- 13 years. The average duration of preoperative dialysis was
      82 +/- 63 months. The average duration of cardiac symptoms before surgery was 35
      +/- 52 months. Twenty-seven patients (54%) were in NYHA functional classes III or
      IV before surgery. Sixteen patients (32%) had preoperative left ventricular
      ejection fractions of less than 0.40. Twelve patients (24%) were emergency
      referrals. Twenty-nine patients underwent isolated coronary bypass surgery, 13
      patients underwent isolated aortic valvular replacement which had to be repeated
      in one case, 3 patients underwent mitral valve replacement, which had to be
      repeated in 2 cases, and 5 patients underwent combined surgery. The average
      aortic clamping time was 75 +/- 32 minutes, the average cardio-pulmonary bypass
      time was 125 +/- 50 minutes. The surgical revascularisation of the coronary
      patients was incomplete in 37% of cases because of the severity of the underlying
      coronary artery disease. The average postoperative bleeding was 800 +/- 650 ml;
      29 patients (58%) were transfused with an average of 4.3 +/- 3 units of blood.
      The global early mortality was 9 patients (18%); 10% in coronary bypass, 7% in
      aortic valve replacement and 50% in patients with more complex procedures. The
      causes of death were cardiac (n = 4), sepsis (n = 2) and multiple organ failure
      (n = 3). The morbidity was 39%, mainly due to low cardiac output.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7646249
TI  - [Doppler echocardiographic evaluation of left ventricular wall stress in aortic
      stenosis].
AB  - The measurement of wall stress allows study of morphological adaptation of the
      left ventricle, especially in conditions associated with symmetric hypertrophy
      (hypertension, aortic stenosis). The calculation is performed in hypertensive
      heart disease but not in aortic stenosis because of the ventriculo-aortic
      pressure gradient. In a preliminary study, the authors validated the peak
      systolic left ventricular pressure calculated by adding the systolic brachial
      artery pressure to the maximal transvalvular pressure gradient by comparing the
      value with that obtained by catheterization in 21 patients with aortic stenosis.
      The second phase of the study was to measure meridian and circumferential wall
      stress prospectively in 35 patients with aortic stenosis (29 symptomatic, 6
      asymptomatic) and to compare the results with those observed in 21 normal
      subjects. In the latter group, the values were 151 +/- 22 and 311 +/- 37 10(3)
      dynes/cm2 respectively, whereas in asymptomatic aortic stenosis the stresses were
      136 +/- 28 and 303 +/- 41 10(3) dynes/cm2 respectively (NS) and in symptomatic
      aortic stenosis 210 +/- 55 and 437 +/- 94 10(3) dynes/cm2 respectively (p <
      0.0001). None of the cases of asymptomatic aortic stenosis had raised wall stress
      values whereas only 6 symptomatic aortic stenosis patients had normal wall
      stress. The values of wall stress obtained using the method proposed were
      comparable to those reported by other authors with invasive investigations. Non
      invasive measurement of wall stress by Doppler echocardiography may be proposed
      as a method of evaluation of left ventricular adaptation, especially in severe
      stenosis and in patients with a patent geometric abnormality (abnormal dilatation
      or even an inadequately hypertrophied wall).

PMID- 7646250
TI  - [Influence of anatomo-pathological involvement of the aorta on results of
      Bentall's operation].
AB  - The results of 51 patients undergoing the Bentall procedure for aneurysmal
      pathology of the ascending aorta during the last 10 years are analysed with
      respect to the nature of the pathology of the lesions of the arterial wall. The
      study population comprised 39 men and 12 women with a mean age of 47 +/- 17 years
      (range 2-76 years). They were divided into two groups, Group I (n = 38) with
      degenerative cystic medianecrosis, Group II (n = 13) with atheromatous lesions.
      The overall results were satisfactory with a hospital mortality of 3.9% and 5 and
      10 year survival rates of 94 and 74% respectively. No difference in results was
      observed with respect to the anatomical site of the aneurysm, the presence of
      dissection or the technique used for repair. The results in degenerative lesions
      (Group I) were excellent but the accent should be placed on prevention to reduce
      the number of patients operated in a context of acute dissection. The presence of
      atheromatous lesions identifies a high risk group (Group II) due to advanced age,
      hypertension and associated vascular and coronary lesions. The hospital mortality
      in this group was 15.4% compared to almost nil when the aneurysmal pathology was
      due to degenerative lesions of the media. The extramortality of this group is
      directly related to the presence of atheromatous lesions (mesenteric infarction
      due to atheromatous embolism) and incites special attention to the mesenteric
      sphere in the postoperative period. The preoperative work-up should include
      transoesophageal echocardiography of the thoracic aortic wall, probably the
      source of the postoperative emboli.

PMID- 7646251
TI  - [Percutaneous pulmonary valvuloplasty in children and adults: immediate results].
AB  - Between April 1987 and December 1993, 60 consecutive patients with valvular
      pulmonary stenosis underwent percutaneous balloon valvuloplasty in the cardiology
      department of Monastir. The average age was 13.9 +/- 10.9 years (3 days-44
      years). Fifteen patients were over 17 years of age and 4 were less than one year
      old. The right ventricular systolic pressure fell from 116.5 +/- 39.5 mmHg to 55
      +/- 19.7 mmHg (p < 0.0001) immediately after the procedure. The peak-to-peak
      systolic gradient between the right ventricle and pulmonary artery fell from 95.4
      +/- 40.2 mmHg to 30.4 +/- 19.0 mmHg (p < 0.00001), the valvular-gradient fell
      from 87.5 +/- 39.6 mmHg to 14.7 +/- 11.1 mmHg (p < 0.00001) and the infundibular
      pressure gradient increased slightly from 8.0 +/- 14.0 mmHg to 15.6 +/- 18.6 mmHg
      (p = 0.06). The systolic pulmonary artery pressure increased from 21.6 +/- 6.0
      mmHg to 25.2 +/- 6.3 mmHg (p = 0.0015). The mean pulmonary artery pressure from
      15.6 +/- 4.8 mmHg to 17.3 +/- 4.9 mmHg (p = 0.028). There were no changes in
      pulmonary diastolic pressures (10.6 +/- 3.7 mmHg vs 9.2 +/- 3.5 mmHg, p = 0.6).
      There were 4 primary failures (6.4%) with residual valvular gradients > or = 30
      mmHg, including one due to valvular dysplasia. No predictive factors of primary
      failure could be identified. An infundibular gradient > or = 20 mmHg was observed
      in 11 patients, 4 of whom had gradients > or = 50 mmHg (6.6%); two gradients were
      residual and 2 were created by pulmonary valvuloplasty.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7646252
TI  - [Coronary angioplasty and electric alternans of the ST segment].
AB  - Alternans of the ST segment is a rare phenomenon during coronary angioplasty. The
      authors report three cases. It is usually observed in left anterior descending
      arteries without collateral circulation. Alternans is not accompanied by
      haemodynamic changes and does not initiate malignant ventricular arrhythmias. It
      is a transient phenomenon. Electrical alternans is thought to be due to changes
      in the configuration of the transmembrane action potential and modifications of
      calcium exchanges.

PMID- 7646253
TI  - [Prevention of deep venous thrombosis].
AB  - The positive and negative clinical symptoms and signs of deep venous thrombosis
      are both insensitive and non-specific. Venography is the reference investigation:
      Duplex ultrasonography is the usual diagnostic procedure for distal deep venous
      thrombosis but it is less reliable in proximal lesions. The sensitivity of
      plethysmography in proximal deep venous thrombosis is high but the diagnosis of
      isolated calf vein thrombosis and non-obstructive proximal thrombosis escape
      diagnosis in this technique. Most cases of deep venous thrombosis occur after
      major surgery, during pregnancy, in the post-partum period, after prolonged
      immobilisation and in obese patients or those with varicose veins. Congenital and
      acquired causes should also be investigated when spontaneous deep venous
      thrombosis occurs or when the condition complicates minor surgical trauma in a
      young patient. The incidence of deep venous thrombosis varies with the type of
      surgical procedure: 25% in general surgery, 50% after hip or knee arthroplasty,
      43% after fracture of femur, 24% after neurosurgery. Graduated pressure stockings
      should be used for the prevention of deep venous thrombosis. Other measures
      include aspirin, dextran, oral and subcutaneous anticoagulants, non-fractionated
      and low molecular weight heparins. The relative efficacy of these different
      measures is discussed with respect to each type of surgical procedure.

PMID- 7646254
TI  - [Current biological surveillance of oral anticoagulant treatment].
AB  - The prothrombin time is the coagulation time of citrated plasma in the presence
      of calcium and a tissue extract, thromboplastin, added in excess. The prothrombin
      time was historically the first method of evaluation and control of oral
      anticoagulation. Over the years, the different thromboplastins have changed,
      diversified, so affecting the result of the prothrombin ration established from
      the prothrombin time and a reference curve. In 1985, the International Committee
      on Thrombosis and Haemostasis requested that all the losts of thromboplastin have
      their international sensitivity index (ISI) indicated. This allowed uniformity of
      the results by the introduction of the INR (International Normalized Ratio)
      calculated by the formula: INR = (PTR)ISI, the PTR or prothrombin time ratio
      corresponding to the patients' prothrombin time divided by that of reference
      control plasma. It is, in fact, impossible to interpret the results of a
      prothrombin ration without knowing their expression in INR. The consequences of
      the absence of uniformity in the control of anticoagulant therapy are important
      and serious. The uncertainty concerning the degree of anticoagulation inherent in
      the use of a single prothrombin ratio may be the source of bleeding or
      thromboembolic complications. Curiously, the system based on the INR is neither
      generalised, nearly 10 years after its recommendation, nor adopted by the
      majority of practitioners. However, the stakes are high because the principal
      complication of oral anticoagulants remains bleeding, including the dramatic
      strokes. Moreover, the global mortality due to haemorrhagic complications is
      about 0.1 to 0.5% for treatments of short duration and much higher in prolonged
      therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7646255
TI  - [New therapeutic prospects in acute coronary thrombosis].
AB  - The principal new clinical approaches to the treatment of acute coronary
      thrombosis are reviewed. They include fibrinogen platelet receptor antagonists
      (anti GP IIb-IIIa) and direct thrombin inhibitors. The anti GP IIb-IIIa have been
      shown to be effective in unstable angina and in the prevention of acute coronary
      occlusion after transluminal angioplasty. Thrombin inhibitors, the leader being
      hirudine, also give promising results. The real clinical benefits of these agents
      and the risk of haemorrhage that they incur in monotherapy or in association,
      will only become clear when the results of large scale trials which are under way
      at present, become available. Other antiplatelet agents (clopidogrel, thromboxane
      inhibitors) are also discussed.

PMID- 7646256
TI  - [Rotablator and endoprosthesis on the left main coronary trunk].
AB  - A 78 year old woman with unstable angina due to significant stenosis of the left
      main coronary artery and occlusion of the right coronary artery was treated
      medically for 29 months because of a surgical contraindication. Resistance to
      drug therapy led to referral for complex angioplasty of the left main, left
      anterior descending and left circumflex arteries, successively by rotablator and
      balloon angioplasty. An immediate elastic recoil on the left main coronary artery
      led to implantation of a Palma-Schatz stent. There were no complications and the
      patient is asymptomatic twenty months later.

PMID- 7646258
TI  - [Sudden death caused by coronary atherosclerosis: consider before you act].

PMID- 7646257
TI  - [Acute myocarditis in non-typhoid Salmonella infection].
AB  - The authors report a case of myocarditis secondary to a Salmonella Virchow
      infection in a 20 year old non-immunodeficient man without a previous medical
      history. The outcome was favourable after treatment with fluoroquinolone. The
      features of this rare complication of non-typhic salmonella infection are
      discussed with respect to this and four other recently published cases.

PMID- 7646259
TI  - [What are the criteria of priority for the patient to be accepted on the waiting
      list for cardiac transplantation?].
AB  - The limited resources (in grafts, human and financial resources) incited the
      authors to carry out a prospective assessment of the value of assessing
      adrenergic function (scintigraphy with meta- iodo- benzyl guanidine, MIBG) for
      the procedure of inscription on the waiting list of patients with cardiac failure
      awaiting cardiac transplantation. The study was undertaken from October 1988 to
      October 1992. Seventy-eight candidates for transplantation were included in the
      study. Forty-six patients with a MIBG cardiothoracic ratio less than 120% were
      placed on the waiting list. In July 1993, 35 had undergone transplantation after
      a 5 months delay. Four patients are still awaiting transplantation and 7 died
      whilst on the waiting list. Thirty two with a MIBG cardiothoracic ratio greater
      than 120% were treated medically: in 14 cases (43%) this decision was reviewed
      after 17 +/- 12 months. The clinical course was stable in the other 18 patients
      with a follow-up of 46 +/- 18 months (range: 12-72 months). In all, the results
      of this study show that a procedure of selection for inscription on the waiting
      list of patients with cardiac failure judged to be good candidates for
      transplantation based on the value of the MIBG cardiothoracic ratio allows
      deferrement of inscription of patients at least risk without changing the chances
      of survival in the whole population group within a 2 year period.

PMID- 7646260
TI  - [Does recanalisation of chronic right coronary occlusion improve long-term
      quality of life and the return to work?].
AB  - Between 1985 and 1990, right coronary artery recanalisation was attempted in 60
      consecutive patients. In order to evaluate the long-term benefits, 2 groups were
      compared: group A (27 patients: 26 men, 1 woman) with an initial success; 1
      patient was lost to follow-up (3.7%); group B (33 patients, 31 men, 2 women) with
      an initial failure; no patients were lost to follow-up and 1 patient died after
      secondary coronary artery surgery. After a follow-up of at least 1 year, the
      patients assessed their health and compared it with their pre-angioplasty state
      with the aid of a questionnaire. Age, initial left ventricular ejection fraction,
      the percentage of multiple vessel disease and the number of patients at work
      before angioplasty were the same in the two groups. After a mean follow-up period
      of two and a half years, 7.6% of patients had undergone coronary bypass surgery
      in group A compared with 18.2% in group B (NS); 69% of patients in group A
      claimed to be improved compared with only 24% in group B (p = 0.07); a bi or
      triple anti-anginal therapy was used in 58% of patients in group B and 42% of
      patients in group A (NS); however, 59% of patients returned to work in group B
      compared with 44% in group A (NS). Initial successful recanalisation of chronic
      right coronary occlusion improves the quality of life at long-term but does not
      increase the chances of returning to work.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7646262
TI  - [Preliminary study of a double chamber pacemaker with diagnostic function].
AB  - Pacemakers with diagnostic functions have been implanted for several years. The
      main clinical indication for these devices is unexplained syncope. Some reports
      of the use of diagnostic pacemakers have shown that in patients with unexplained
      syncope, paroxysmal bradycardia was a common finding after implantation. Until
      recently, diagnostic functions were only available in VVI pacemakers, which
      explains the limitations of this type of function in determining the mechanism of
      the bradycardia. The aim of this study was to assess a new dual-chamber
      diagnostic pacemaker functioning in the VDI mode. Twenty-three patients were
      implanted with this type of unit and followed up for an average of 153 days. The
      number of episodes of bradycardia detected was 6 +/- 10 (median: 3). The interval
      between the installation of the algorithm and the date of the first episode of
      bradycardia was 67 +/- 86 days (range: 12-306 days). The mechanisms of the
      bradycardia were atrioventricular block (6 patients), sinus node dysfunction (6
      patients) and blocked atrial bigeminy in 1 patient. These conclusions were drawn
      from analysis of chains of markers. Bradycardia was recorded during the day or
      during the day and night in 21 patients; bradycardia was exclusively nocturnal in
      only 2 patients. The tolerance of the algorithm was good on the whole but 3
      patients reported minor symptoms related to the relative bradycardia inherent
      with this type of algorithm. Four other patients had a VDI pacemaker syndrome
      which was completely corrected by reprogramming the pacemaker to the standard DDD
      mode. These new devices represent a technical advance in the field of diagnostic
      pacemakers.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7646261
TI  - [Adaptation to effort in patients with chronic cardiac insufficiency; study by
      post-exercise Doppler echocardiography, comparative results with a control
      population].
AB  - Adaptation to exercise was studied by post-exercise Doppler echocardiography in
      patients with chronic cardiac failure and an apparently healthy control
      population matched for age. This post-exercise Doppler echocardiographic method
      initially introduced for the detection of myocardial ischaemia has already been
      validated in normal subjects for the analysis of haemodynamic changes caused by
      exercise providing the data is recorded in the first 5 minutes following recovery
      in the recumbent position. Eleven patients with chronic cardiac failure in NYHA
      classes II or III with a mean age of 54 +/- 11 years and 6 controls (mean age: 46
      +/- 9 years) were investigated. The patients had been stabilised for at least 3
      months with a vasodilator and diuretic therapy: the control subjects had no
      medication. After bicycle ergometry performed to 70% of maximum capacity, the
      subjects were positioned in the left lateral recumbent position. Doppler
      echocardiography was then performed in the immediate recovery phase. When
      compared to the control population, the patients with cardiac failure had a
      reduced chronotropic reserve, a smaller increase in the parameters of myocardial
      contractility (maximal aortic velocity, maximal aortic acceleration and left
      ventricular fractional shortening) without an increase in left ventricular end
      diastolic dimensions in subjects with severe dilatation under basal conditions
      (left ventricular end diastolic dimension 69 +/- 3 mm). This result suggests the
      absence of a Frank-Starling effect. The lack of adaptation of the peripheral
      vascular system was demonstrated by the lack of reduction of left ventricular end
      systolic stress, already greatly increased at rest (176 vs 77 +/- 10 g/cm2 for
      patients, compared with controls; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7646263
TI  - [Antiaggregants, aspirin, myocardial infarction and coronary deaths in the Haute
      Garonne area].
AB  - The aim of this study was to determine changes in treatment of myocardial
      infarction between 1986 and 1989 in the Haute-Garonne region and, in particular,
      to assess the role of aspirin and antiaggregant therapy. The cases of 416
      patients admitted to hospital for myocardial infarction in 1986 and 1989 were
      reviewed. During this period the prescription of acetylsalicyclic acid during the
      acute phase of myocardial infarction increased threefold (26.4 vs 72.9%; p <
      0.001) and fivefold when associated with fibrinolytics, coronary bypass or
      angioplasty. Similarly, the prescription of aspirin at the time of hospital
      discharge doubled (from 32.6 to 69.5%; p < 0.001). The dosage of aspirin
      decreased from 500 mg and more per day in 1986 to a dosage of 250 mg or 100 mg
      per day in 1989. The most commonly prescribed preparation is lysine
      acetylsalicylate. The hospital mortality in the Haute-Garonne between 1985 and
      1989 has decreased as observed in the Haute-garonne centre of the MONICA project.
      During the same period, the prescription of aspirin in association with
      angioplasty, bypass surgery and fibrinolytics, has undergone a remarkable
      increase. The changes observed during this period of observation are in perfect
      accord with results already published of therapeutic trials of antithrombotic
      agents in the acute phase or the post-infarction period (ISIS 2).

PMID- 7646264
TI  - [Should a signal-averaged electrocardiogram be requested in the evaluation of
      malaise and syncope?].
AB  - In order to determine whether signal-averaged electrocardiography was useful in
      the diagnosis of syncopal ventricular tachycardia, 244 subjects with malaise or
      unexplained syncope without documented ventricular tachycardia underwent
      endocavitary electrophysiological study and signal-averaged electrocardiography
      with a 25 Hz bandpass filter. Ninety-three patients had no apparent cardiac
      disease whereas 151 patients had cardiac problems. ventricular tachycardia was
      induced in 91 patients. Fifty-two of them (57%) had ventricular late potentials.
      Twenty-two patients without inducible ventricular tachycardia also had late
      potentials (14%). The diagnostic value of signal-averaged electrocardiography
      depended on the cardiac disease: in the absence of cardiac disease, its
      sensitivity was poor (31%) but the specificity was excellent (96%). In the
      presence of cardiac disease, the sensitivity improved (63%) but the specificity
      was not as good (67%). The lack of sensitivity in the group with cardiac disease
      generally concerned subjects with inducible rapid ventricular tachycardia. The
      authors conclude that signal-averaged electrocardiography should not be requested
      in the investigation of unexplained syncope in subjects without cardiac disease
      to demonstrate abnormal ventricular excitability which is very rate in these
      subjects. On the other hand it is more valuable in those with underlying cardiac
      disease although inducible rapid ventricular tachycardia may still escape
      detection.

PMID- 7646267
TI  - [Hypersensitivity and resistance to antivitamins K].
AB  - During the initial phase or during treatment with oral anticoagulants,
      hypersensitivity or resistance may be observed, requiring significant changes in
      prescribed dosage. A thorough knowledge of the mode of action of vitamin K and
      its antagonists is useful to improve understanding of unexpected response to oral
      anticoagulant therapy. These abnormal responses may be due to poor compliance to
      treatment by the patient, insufficient or excessive vitamin K intake,
      interference with other drugs or abnormalities of the hepatic enzymes which are
      the target of oral anticoagulant drugs. The search for a cause is justified by
      the risks associated with these abnormal responses. It must be rigorously
      undertaken with an accurate interrogation, use of an anticoagulation monitoring
      leaflet and, if necessary, measurement of plasma concentrations and
      pharmacokinetics of the anticoagulant drug.

PMID- 7646266
TI  - [Diabetic cardiomyopathy].
AB  - Type I and type II diabetes is associated with increased cardiovascular
      complications, the most common of which are ischaemic cardiomyopathy and left
      ventricular dysfunction. The existence of an independent disease, diabetic
      cardiomyopathy, was suggested by initial anatomic studies, experimental models,
      and, more recently, by epidemiological studies. The exact cause of this
      ventricular dysfunction is not known: several mechanisms have been proposed, such
      as metabolic abnormalities of glucose transport, cellular overload in fatty acid
      metabolites, alteration of calcium uptake by the sarcoplasmic reticulum leading
      to cellular calcium overload, coronary microangiopathy, structural collagen
      abnormalities, interstitial and perivascular fibrosis or the presence of an
      autonomic neuropathy. The condition is characterised by abnormal left ventricular
      filling suggesting poor compliance or prolongation of left ventricular
      relaxation. Left ventricular systolic function is usually normal at rest but
      abnormally decreased on effort. The value of strict metabolic control and the
      place of drug therapy, especially calcium antagonists which oppose cellular
      calcium overload, has yet to be established. The natural history of diabetic
      cardiomyopathy should be defined by clinical studies taking care to differentiate
      it from the cardiovascular consequences of hypertension or obesity which
      aggravate or stimulate this condition.

PMID- 7646268
TI  - [Infarction in young women caused by intracoronary thrombosis on angiographically
      normal arteries: apropos of a case].
AB  - Myocardial infarction is a rare clinical event in young women. The usual
      presentation is similar to that of older adults. The authors report a case of
      anteroseptal infarction in a 24 year old woman presenting with paroxysmal
      epigastric pain without irradiation with fever, during menstruation. The
      electrocardiogram was compatible with acute pericarditis. The diagnosis was
      rectified by echocardiography which showed anteroseptal akinesia. Coronary
      angiography performed as an emergency showed a radiolucent mobile image in the
      mid segment of the left anterior descending artery with appearances of a distal
      embolism which were attributed to thrombosis. Intracoronary thrombolysis was
      associated with a good outcome.

PMID- 7646265
TI  - [Quantification of aortic insufficiencies. Comparison between Doppler
      echocardiography and qualitative angiographic methods: apropos of a series of 60
      consecutive patients].
AB  - Many doppler echocardiographic indices have been described for quantifying aortic
      regurgitation, posing the problem of the relative value of each. Therefore, the
      authors assessed the severity of aortic regurgitation in 60 consecutive patients
      (16 women and 44 men, mean age 56.7 years, range 7 to 84 years) by the four
      grades of Seller's classification with selective aortography. These results were
      compared with Doppler echocardiographic measurement of anterograde cardiac output
      (Qao), the pressure half time (PHT), diameter of the jet at its origin in M mode
      colour Doppler (DTM) and calculation of the regurgitant fraction (RF) by
      comparison of flow at the different cardiac orifices by a method previously
      described and validated in the author's laboratory with an interorifice
      correlation of 0.91 to 0.96 and confidence intervals at 95% of the order of 12%.
      The feasibility of doppler echocardiographic methods was good: 87.8% for PHT
      (58/66 patients), 90% for DTM (36/40 patients), 90.9% for Qao and RF (60/66
      patients). The correlation with aortography was -0.65 (p < 0.01) for PHT; 0.91 (p
      < 0.01) for DTM, 0.80 (p < 0.01) for Qao and 0.92 (p < 0.005) for RF. However,
      there was a number of overlaps between Grades I and II and Grades III and
      IV.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7646269
TI  - [Pulmonary arterial hypertension and primary biliary cirrhosis].
AB  - The authors report a case of the association of primary biliary cirrhosis and
      pulmonary hypertension presenting with syncopal complete atrioventricular block.
      The clinical, aetiopathological and therapeutic aspects of this pathology are
      reviewed with special emphasis on the value of early diagnosis of the pulmonary
      hypertension in cases of unusual dyspnoea in patients with primary biliary
      cirrhosis especially those of an age when they could benefit from liver-heart
      lung transplantation.

PMID- 7646270
TI  - [Malignant tumoral lymphoma of the heart in human immunodeficiency virus
      infection: diagnosis by echocardiography].
AB  - Non-Hodgkin's lymphoma is common in patients with human immuno-deficiency virus
      infection, but an intracardiac localisation is rare. In this case, the malignant
      lymphoma presented with a degradation of the patient's condition and signs of
      right-sided cardiac failure. Echocardiography showed a polylobed mass invading
      the right ventricle. Computerised tomography provided detailed information of the
      extension of the lymphoma in the different cardiac chambers. The patient died
      after a few days of a low cardiac output state. The malignant nature of the
      tumour was confirmed at biopsy. This case of cardiac lymphoma in a patient with
      immunodepression confirms the fatal character of this condition in the very short
      term after the appearance of the first clinical signs, the value of
      echocardiography in the diagnosis and the difficulty in implementing any
      effective therapeutic measure.

PMID- 7646271
TI  - [Coxiella burnetii endocarditis on a mechanical valvular prosthesis. Apropos of 2
      cases].
AB  - The authors report two cases of prosthetic valve endocarditis due to Coxiella
      burnetii. The histories were chronic and complex suggesting an auto-immune
      disease: prolonged recurrent fever despite antibiotic therapy with a biological
      inflammatory syndrome whilst blood cultures remained negative. The first patient
      presented with prosthetic valve dehiscence and acute glomerulonephritis. The
      second patient had coagulation defects with prosthetic valve thrombosis,
      mesenteric adenopathy and congestive cardiac failure without prosthetic valve
      dysfunction. In suspected endocarditis with negative blood cultures, serological
      tests should be extended to intracellular pathogens difficult to identify and
      justifying specific and prolonged bactericidal therapy (fluoroquinolones,
      cyclines, rifampincine). Long-term serological surveillance is essential even
      when the outcome could have led to the termination of antibiotic therapy.
      Usually, antibiotic therapy provides a bacteriological cure, but treatment has to
      be continued for at least 3 years, and, in some patients, all their lives. Valve
      replacement is reserved for haemodynamic complications of the pathology which
      determine the ultimate prognosis.

PMID- 7646272
TI  - [Percutaneous extraction of a silicone catheter 5 years after its migration in
      the pulmonary artery].
AB  - The authors describe a case of percutaneous extraction of a piece of silicone
      coated catheter, 5 years after its embolisation in the pulmonary artery and the
      results of electronic microscopic study of the specimen. The discussion provides
      the factors indicating extraction which is relatively easy with this technique
      irrespective of the chronicity of embolisation, in order to avoid infectious
      complications.

PMID- 7646273
TI  - [Myocardial infarction following rapid perfusion of corticoids].
AB  - The authors report the case of myocardial infarction occurring immediately after
      rapid intravenous infusion of a high dose of corticosteroids prescribed for a
      relapse of multiple sclerosis. Ventriculography confirmed the myocardial damage
      but the coronary arteries were normal. An aetiological investigation was
      negative. The authors review the cardiac secondary effects which may be very
      serious and even fatal. Coronary insufficiency is rare (only 3 previously
      published cases); it is therefore difficult to determine the prognosis. The
      possible mechanisms of infarction are discussed. Finally, the authors underline
      the importance of recording an ECG before treatment, of ECG monitoring during the
      infusion, and the need for repeating the recordings and of prolonging hospital
      admission when necessary.

PMID- 7646274
TI  - [Gene localisation in 12q12 in Holt-Oram atrio-digital syndrome].
AB  - The Holt-Oram syndrome, first described in 1960, consists of non-cyanotic
      congenital heart disease, usually an atrial septal defect, arrhythmias and
      malformations of the upper limbs affecting the radial segment. The transmission
      of the syndrome is autosomal dominant with almost complete penetrance. The
      authors report the localisation of a genetic abnormality of the Holt-Oram
      syndrome on the long arm of chromosome 12 (12q21-q3) by analysis of linkage in 9
      multiplex families (Zmax = 8.19 at locus D12S354). Multipoint analysis showed a
      genetic interval of 7 centimorgans containing a gene of the Holt-Oram syndrome
      between loci D12S84 and D12S79 (multipoint lod score, 10 g base 10 = 8.96). In
      situ hybridization of artificial yeast chromosomes containing the surrounding
      markers showed that a gene of the Holt-Oram syndrome is located in 12q23-q24. The
      genetic heterogeneity was demonstrated in 3 families of the Holt-Oram syndrome
      with polydactyly or without cardiac disease (homog-test: chi 2 = 13.28; p =
      0.0001). The localisation of a gene of the Holt-Oram syndrome is, to the authors'
      knowledge, the first chromosomal localisation of a cardiac malformation with
      septal defects in man. The identification of this gene should open wide
      perspectives for genetic research of cardiac morphogenesis and clarify the
      molecular mechanisms which govern cardiac septation during embryogenesis.

PMID- 7646275
TI  - [Natural history of hypertrophic obstructive cardiomyopathy in young patients:
      apropos of 40 cases].
AB  - This retrospective study analysed the outcome of children with hypertrophic
      obstructive cardiomyopathy. Between 1969 and 1992, 40 patients all under 20 years
      of age (mean = 10.9 +/- 6.2 years) were followed up for this condition. There was
      a positive family history of hypertrophic cardiomyopathy and/or sudden death in
      21 cases (53%); 21 (53%) were symptomatic: > NYHA Stage II dyspnoea (n = 13);
      chest pain (n = 8); syncope (n = 7) or palpitations (n = 4). Thirty-two patients
      were treated by betablockers, 1 by verapamil, 2 by amiodarone (associated with
      propranolol in 1 case); 7 patients underwent surgery and 6 others, asymptomatic,
      had no specific treatment. The mean follow-up period was 10.2 +/- 6.2 years with
      no drop-out: 13 patients died (1 non-cardiac death, 2 of unknown causes and 10 of
      cardiac causes, including 8 sudden deaths) giving an annual global mortality of
      3.2%; the actuarial 5 and 10 year survival rates were 90 and 85% respectively.
      The 27 survivors were compared with the 13 patients who died: of the 11 clinical
      and paraclinical criteria examined, only a previous history of syncope correlated
      with global mortality (p = 0.004) and sudden death (p = 0.0008).

PMID- 7646276
TI  - [Agenesis of the pulmonary valves. Experience over 20 years].
AB  - Absent pulmonary valve is a rare cardiac malformation, usually associated with a
      tetralogy of Fallot. It features aneurysmal dilatation of the pulmonary arteries
      which may compress the bronchial tree and lead to respiratory distress. The
      experience of our group over a 20 year period (20 patients) is reported. The
      diagnosis was usually made in the neonatal period in the presence of cardiomegaly
      and a systolic and diastolic murmur at the left sternal border. The diagnosis was
      made at antenatal echocardiography in 2 cases. Ten patients were not operated and
      4 of them died in the neonatal period of respiratory distress and 2 others of
      extracardiac causes. Three children are on the waiting list for surgical
      correction and the remaining child is asymptomatic. The other 10 cases were
      operated with a minimum closure of the ventricular septal defect and widening of
      the pulmonary tract. The latter procedure was performed with an infundibulo
      pulmonary patch (6 cases) and insertion of a pulmonary valve (4 patients)
      (monocusp patch in 3 cases, pulmonary heterograft in one case). Eight patients
      underwent a reduction procedure of the pulmonary arteries to relieve branchial
      compression. Of those who were operated, two died during follow-up: the first of
      complete atrioventricular block and the second of infectious endocarditis of the
      stenosed pulmonary heterograft. These results show that reduction procedures of
      the pulmonary arteries are promising approaches which should improve the future
      prognosis of young patients with respiratory distress. The need for insertion of
      a pulmonary valve remains debatable.

PMID- 7646277
TI  - [Pulmonary atresia with ventricular septal defect: therapeutic strategy in
      newborn infants].
AB  - Pulmonary atresias with ventricular septal defect, a right ventricular
      infundibulum and pulmonary artery separated by an imperforated membrane and a
      complete pulmonary tree with two branches in continuity are called "favourable"
      forms of this malformation. The authors studied 29 neonates, less than 1 month
      old, in whom the malformation was both ductus- and prostaglandin-dependent,
      prostaglandin infusion being essential for pulmonary flow and impossible to stop
      because of the resulting severe hypoxia. The choice of treatment depended on the
      anatomical form defined by angiocardiography. In the 19 regular forms with
      regular pulmonary arteries with little hypoplasia, percutaneous perforation
      dilatation was successful in 3 out of 5 attempts with one secondary death and 2
      good results leading to complete repair; anastomosis was performed in 9 cases
      with 3 deaths, 1 partial result and 5 good results which were followed by
      complete repair in 3 cases; primary complete repair attempted in 7 cases led to 1
      death and 6 successes completed in 3 cases by reoperation for left pulmonary
      artery stenosis. In the 10 less favourable anatomical forms with stenosis or
      severe hypoplasia or the pulmonary branches, only palliative procedures were
      proposed: 2 perforations-dilatations which only gave partial results, 7
      anastomoses with 1 death and 4 partial results; and 1 ventriculo-pulmonary
      connection without closure of the ventricular septal defect (good result). In
      view of the good results obtained over the 6 years of the study, the authors
      advise primary complete correction for the anatomically favourable forms of the
      malformation when weaning from prostaglandin infusion is impossible.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7646278
TI  - [Comparative value of transthoracic echocardiography and angiography for
      measuring the pulmonary artery annulus in tetralogy of Fallot].
AB  - It may be necessary to perform an enlarging pulmonary annuloplasty during
      surgical cure of Tetralogy of Fallot (TOF) in order to optimise reconstruction of
      the right ventricular outflow tract. As this additional procedure implies an
      increase in perioperative mortality, it is useful to prepare for this eventuality
      before surgery. Two imaging techniques are available: transthoracic
      echocardiography (diameter of the pulmonary annulus obtained by averaging the
      measurements obtained in the subcostal and parasternal short axis views of the
      insertion of the pulmonary valve cusps at end systole) and selective angiography
      during right heart catheterisation (anteroposterior measurement with comparison
      to be projected and real size of the catheter at the point of insertion of the
      cusps at end systole). In this study, these two techniques were compared with
      reference to the peroperative measurement with Hegar dilators and criteria
      defined by Naito (minimal diameter of the pulmonary artery annulus with respect
      to the weight of the child). Seventy-eight children admitted to hospital between
      January 1986 and April 1994 for curative surgery of TOF were included. The
      calculation of the intra-class correlation coefficient showed a mediocre
      correlation with angiography and a very mediocre correlation with
      echocardiography compared with peroperative measurements. However, the
      calculation of sensitivities showed angiography to be the predictive
      investigation for annuloplasty in children not conforming to the Naito criteria:
      higher sensitivity (83% vs 26% for echocardiography), greater negative predictive
      value (84% vs 70%). This result holds for all categories of body weight (over and
      under 10 kg).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7646280
TI  - [Transposition of great vessels with position anomaly of the atrioventricular
      valves or chordae: echocardiographic aspects and surgical correlations].
AB  - The authors report the echocardiographic appearances of 27 cases of transposition
      of the great arteries (TGA) with ventricular septal defect (VSD) (including the
      Taussig-Bing malformation) complicated by displacement of one or both
      atrioventricular valves and/or chordae tendinae diagnosed between September 1985
      and September 1994. An anatomical repair was performed in 21 cases and allowed
      accurate correlation of the echocardiographic and peroperative findings; a cavo
      bipulmonary conduit or a palliative procedure was performed in 6 cases. The cases
      were classified in 3 groups: group I: 16 children with isolated tricuspid valve
      abnormalities; group II: 7 cases of mitral valve straddling; group III: 4 cases
      of displacement of both atrioventricular valves and/or their chordae. The cases
      of group I were divided into 3 subgroups: subgroup Ia with insertion of the
      tricuspid chordae on the infundibular septum (7 cases); subgroup Ib with isolated
      overriding of the tricuspid valve (2 cases); subgroup Ic straddling with or
      without overriding of the tricuspid valve (7 cases). In all three groups, there
      were 10 cases of straddling of the tricuspid and 11 cases of straddling of the
      mitral valve: 9 type A, 3 type B and 9 type C of Tabry's classification.
      Echocardiography misdiagnosed one case of type A straddling of the tricuspid
      valve for a type A overriding and straddling of the mitral valve. The ventricular
      septal defect was situated in the admission septum in the 10 cases of straddling
      of the tricuspid; in the 11 cases of straddling of the mitral valve the chordae
      passed through the superior anterior part of the interventricular
      septum.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7646279
TI  - [Systemic pulmonary shunts in the neonatal period. Short and medium-term
      results].
AB  - Systemic pulmonary shunts were performed in 41 consecutive neonates with
      congenital cyanotic heart disease between 1981 and 1992. The lesions comprised
      pulmonary atresia with intact interventricular septum (16 cases), pulmonary
      atresia with ventricular septal defect (9 cases), tetralogy of Fallot (5 cases),
      transposition of the great arteries (3 cases) and different complex cardiac
      lesions (8 cases). A polytetrafluoroethylene tube was used in 40 neonates, 5 mm
      in diameter in 39 cases, anastomosed to be subclavian artery in 21 patients
      (group A) and on the ascending aorta or innominate artery in 19 patients (group
      B). A retrospective analysis of the results was undertaken in all patients with a
      mean follow-up period of 6.5 years (range: 19 months-12.5 years). There were 4
      early deaths (9.7%) and 8 late deaths (19.5%) giving a total mortality of 29.2%.
      Of the late deaths, 4 occurred in the first year, 3 suddenly at home and 4 in
      relation with the surgical correction. Occlusion of the shunt was suspected in
      only one case. The actuarial survival rate was 78% at one year, 75.5% at 7 years
      and 66% at 10 years. Eleven of the 12 deaths were in children with pulmonary
      atresia with intact interventricular septum (8 cases) and complex cardiac
      malformations (3 cases). Early complications were observed in 15 of the 37
      survivors of the initial procedure. Cardiac failure occurred in 83% of group B
      and 22% of group A (p < 0.01). The probability of shunt efficacy was 89% at 1
      year, 63% at 2 years and 45% at 3 years.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7646281
TI  - [Closure of patent ductus arteriosus by video-thoracoscopy in 45 children].
AB  - For over 20 years, different methods of interventional catheterisation have
      partially replaced surgical closure of patent ductus arteriosus (PDA). The
      authors report the results of a new operative technique, video-thoracoscopy,
      derived from endoscopic surgery. Under general anaesthesia and after tracheal
      intubation, two trocarts of 5 mm diameter are introduced into the thorax for the
      passage of the instruments required for dissection and closure of the PDA. Two
      hooks are also introduced to retract the lung and dissect the ductal region. Two
      9 mm titanium clips are positioned under videoscopic control. Forty-five children
      underwent this procedure between February 1992 and July 1994. The average age at
      the time of operation was 13.8 months (range: 3 to 32 months) with an average
      weight of 14.5 kg (range: 2 to 48 kg) including 10 (22%) with a body weight of
      less than 6 kg. The surgical indications were haemodynamic in 27% of cases (large
      shunts with pulmonary hypertension) and prophylactic against endocarditis in 73%
      of cases. There were no operative fatalities. The immediate complications
      included: chylothorax (1 case) and left recurrent nerve paralysis (2 cases). A
      residual shunt was observed in 3 of the 45 cases (6%). In one of these cases, a
      supplementary clip was effective in suppressing the residual shunt. In the other
      2 cases, the residual shunt was respected after a second failure of clipping the
      duct in one of the cases. The final closure rate was 95.6%. Closure of PDA by
      video-thoracoscopy is a rapid and safe technique.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7646282
TI  - [Percutaneous dilatation of recurrent coarctation of the aorta in the 1st year of
      life].
AB  - It is not rare for surgery of coarctation of the aorta to be complicated by
      recurrence of the lesion at medium-term, especially when it is performed very
      early in life. Advances in interventional catheterisation now offer an
      alternative to surgical reoperation. This study is a retrospective analysis of
      balloon angioplasty in 20 patients in whom isthmic stenosis had been operated
      before the age of one month in 19 cases, in whom recurrent coarctation was
      identified 3.2 +/- 2.1 months later. The percutaneous angioplasty was performed
      by a femoral arterial approach at an average age of 5.4 +/- 2.3 months. The
      femoral pulses returned together with a fall in the transisthmic systolic
      pressure gradient from 58.3 +/- 23.4 mmHg to 18.3 +/- 12.5 mmHg, and the isthmic
      lumen increased by +117 +/- 52%. Judged by the residual pressure gradient, the
      results were good, the best results being observed in the shortest and most
      severe stenoses. After a maximum follow-up of 5 years (average: 20.1 +/- 16.6
      months), the angioplasty was successful in 14 cases (70%), 4 cases had a mild
      residual gradient (20%) and 2 were failures (10%). None of the patients required
      reoperation. There were no fatalities or early aneurysmal complications in the
      dilated zone monitored by echocardiography and magnetic resonance imaging. The
      only complication was femoral artery obstruction (6 cases) which was successfully
      thrombolysed in 5 cases but which recurred at long-term in 3 cases.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7646283
TI  - [Pulmonary artery banding in the treatment of univentricular heart. Results and
      therapeutic implications for cavopulmonary derivations].
AB  - Eighty-six children under one year of age with univentricular hearts associated
      with increased pulmonary flow underwent pulmonary artery banding as the first
      stage of palliative therapy. Fifteen patients also had treatment of coarctation
      of the aorta at the same time and an atrial septal defect was treated in 13
      patients. Twenty-seven patients underwent a Fontan procedure secondarily. The
      mean follow-up was 42.6 +/- 45.5 months; 8 patients were lost to follow-up.
      Twenty-three patients died during the whole of the study period. The global
      actuarial survival rate was 69.6 +/- 5% at 5 years. The 3 year survival rate was
      56 +/- 12% in patients with anatomical right ventricles compared with 74.4 +/-
      5.7% and 69.5 +/- 7.3% at 3 and 5 years respectively in those with anatomical
      left ventricles (p < 0.01). The presence of coarctation of the aorta reduced the
      5 year actuarial survival rate to 25.4 +/- 12.8% (p < 0.01). Subaortic stenosis
      either at the time of initial presentation or occurring during pulmonary banding
      was associated with a 5 year survival of 58.3 +/- 13.7% (p < 0.01). Uni- and
      multivariate analysis demonstrated poor prognostic risk factors. On univariate
      analysis, they were the residual mean pulmonary pressures after banding,
      coarctation of the aorta, subaortic stenosis and a restrictive atrial septal
      defect. Independent risk factors on multivariate analysis were the residual
      pulmonary pressures after banding, coarctation of the aorta, the necessity of
      operation in the neonatal period and the need for reoperation for reason other
      than for a cavopulmonary connection. The feasibility of a Fontan procedure was
      reduced when subaortic stenosis was observed at any time. Only 17.5% of patients
      were free of reoperation during this study for whom banding remained the only
      palliative procedure. In conclusion, a programme of cavopulmonary connection
      should be envisaged from the initial presentation of these patients. The
      different stages of treatment with this objective in mind should aim to preserve
      myocardial function and keep pulmonary resistances low. Therefore, pulmonary
      artery banding should be rejected in cases with coarctation of the aorta and/or
      subaortic stenosis. Similarly, early conversion with a Glenn type bidirectional
      anastomosis allows adaptation of myocardial function for a secondary total
      cavopulmonary connection.

PMID- 7646284
TI  - [Therapeutic strategy in newborn infants with multivisceral failure caused by
      interruption or hypoplasia of the aortic arch].
AB  - Left heart obstructive lesions, in particular interrupted aortic arch or severe
      forms of coarctation with hypoplasia of the aortic arch, are the main cause of
      cardiac failure in the neonate and are often at the root of multiple organ
      failure which worsens the prognosis. Based on a retrospective study of 35
      neonates admitted between July 1984 and June 1994, the authors attempted to
      identify the prognostic factors for admission to the intensive care unit and the
      optimal timing for operation of these patients. All neonates with a ductus
      dependent aortic obstructive lesion and severe multiple (at least four) organ
      failure, were included in the study. There was a high mortality (54%) including
      firstly 7 patients who died in the three days following admission to the
      intensive care unit (20%); this was so-called "medical" mortality for which there
      was no identifiable poor prognostic factor. On the other hand, the surgical
      mortality (12 out of 28 cases, 43%) was significantly different in neonates
      operated before recovery from multiple organ failure (72%) and those operated
      after recovery from multiple organ failure (17%). Based on these results, the
      authors propose a therapeutic strategy based on prolonged preoperative intensive
      care until the initial multiple organ failure is reversed rather than early
      surgery.

PMID- 7646285
TI  - [Long-term efficacy and tolerability of amiodarone in children].
AB  - The authors reviewed the files of 37 patients under 15 years of age (22 boys and
      15 girls) in order to study the long-term efficacy and tolerance of amiodarone
      therapy. The mean age of the patients at the time of initiation of amiodarone was
      6.2 +/- 4.7 years. Amiodarone was prescribed at a loading dose of 500 mg/m2 and
      at a maintenance dose of 250 mg/m2. This drug was prescribed in second intention
      in 29/37 patients and as monotherapy in 15/37 patients. The treated arrhythmias
      were supraventricular in 25 patients (atrial: 10; junctional: 15) and ventricular
      in 12 patients. Underlying cardiac disease was present in 21/37 patients (57%)
      and the arrhythmias were postoperative in 14/37 cases (38%). Efficacy and
      tolerance of amiodarone were estimated on clinical and biological data, the
      results of Holter monitoring, ophthalmological slit-lamp examination and thyroid
      function tests. The average duration of therapy was 4 +/- 3 years. The efficacy
      of amiodarone was judged to be good in 59% and satisfactory in 38% of cases.
      Secondary effects and complications included: corneal deposits: 14 cases (38%);
      skin pigmentation: 1 case; photosensitivity: 10 cases (27%). There was a high
      incidence of thyroid disorders: 7 cases (19%) with 4 cases of biological or
      clinical hyperthyroidism and 3 cases of clinical or biological
      hypothyroidism.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7646286
TI  - [Congenital long QT syndrome: an elective indication for betablocker treatment.
      Apropos of 5 cases].
AB  - The authors report 5 cases of the long QT syndrome. The patients had malaises and
      syncopes triggered by exercise or emotional stress, occurring before 10 years of
      age. The diagnosis was delayed by an average of 38 months (range: 2 to 72 months)
      from the first symptom and systematic familial study which was positive in 4 of
      the 5 cases. The corrected QT intervals varied from 0.46 to 0.56 second. All
      patients were prescribed the betablocker nadolol, resulting in total regression
      of symptoms with no deaths during an average follow-up period of 40 months
      (range: 26 to 64 months). The long QT syndrome is a rare hereditary disorder
      comprising several entities. Recent genetic advances have improved our
      understanding of the condition. All have an idiopathic prolongation of the QT
      interval (> 0.44 second) in common with a predisposition to syncope due to
      torsades de pointes which may cause sudden death. The spontaneous arrhythmic
      mortality, which was early and high, has been remarkably decreased by betablocker
      therapy, from 73% to 6% at 10 years. The authors find nadolol to be extremely
      reliable and well tolerated, and recommend it as the drug of choice in this
      indication.

PMID- 7646287
TI  - [Outcome of 77 live born children with cardiac or rhythmic anomalies diagnosed in
      the prenatal period. Apropos of 77 cases].
AB  - Seventy-seven live born children (September 1988 to May 1993) had prenatally
      detected morphological cardiac malformations (61 cases) and/or arrhythmias (17
      cases). The outcome of these children was analysed with an average follow-up of
      21.4 months (range: 1 day to 11 years). The parameters studied were age and
      condition of prenatal diagnosis, the term of pregnancy, the extracardiac
      malformations associated and the outcome of the live born children. Fifty-two
      children survived with a mean follow-up of 28.2 months (range: 5 months to 11
      years) and 25 children died at a mean age of 3.3 months (range: 1 day to 32
      months). The cardiac malformations correlated with the postnatal diagnosis in 59
      children (60 cardiac malformations). They included left or right outflow tract
      obstruction in 22%, septal defects or Tetralogy of Fallot with or without
      pulmonary atresia in 18.4%, arterial malposition in 12.9% and arrhythmias or
      conduction defects in 20.7% of cases. The main reason for the high mortality was
      the complexity of the cardiac malformations with, in particular, ventricular
      hypoplasia with right or left outflow tract obstruction (41% of mortality). The
      functional consequences of these abnormalities were only partially appreciated at
      prenatal diagnosis. The extracardiac malformations, more easily diagnosed,
      contributed less to this mortality rate. The favourable prognosis of the
      arrhythmias or conduction defects diagnosed prenatally was confirmed but was,
      however, associated with a mortality rate of 12%.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7646288
TI  - [Acute infectious myocarditis in children. Apropos of 2 series from Lyon].
AB  - Acute infectious myocarditis in childhood has a very poor initial outcome, but
      the long-term outlook is relatively good for the survivors. This retrospective
      study was based on cases of acute myocarditis admitted to two hospital
      departments with different modes of recruitment. Firstly, a polyvalent paediatric
      intensive care unit where 12 children (mean age 12 months) were admitted during
      the acute phase of myocarditis. The initial symptoms were non-specific and
      misleading, the diagnosis being established at autopsy in 9 cases. Only 4
      children presented with typical cardiac failure. The clinical signs were
      hepatomegaly, sinus tachycardia, cardiomegaly, ECG ST-T wave changes and
      biological signs of multiple organ failure. Left ventricular function was very
      poor with a fractional shortening of only 17%. The causal agent was usually
      viral. The clinical course was marked by a high early mortality (11/26, 42%)
      within 23 hours of hospital admission. Secondly, a paediatric cardiology unit
      where 81 children (mean age 15 months) were followed up after acute infectious
      myocarditis. Thirteen cases were taken from our first series and were included
      for long-term follow-up; 76.5% had premonitory signs of infection and 71% were in
      cardiac failure, Classes III or IV, during the hospital admission. The causal
      agent was identified in 30 cases (37%) and was usually a virus (22 cases).
      Treatment was classical (association of digitalis, diuretics, angiotensin
      converting enzyme inhibitors, anticoagulants and beta-sympathomimetics when
      necessary).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7646289
TI  - [Persistence of spongy myocardium: apropos of a case].
AB  - A two and a half year old child was admitted to hospital with peripheral
      cyanosis. Echocardiography revealed severe dilated cardiomyopathy affecting both
      ventricles with abnormally hypertrophied and irregular myocardial walls. The
      pulmonary hypertension was suprasystemic with raised pulmonary resistances. The
      magnetic resonance imaging and angiography confirmed the diagnosis of persistence
      of spongy myocardium. This is a rare abnormality due to the persistence of
      embryonic myocardium with a network of trabeculations and intertrabecular spaces
      as usually observed during echocardiography. This case is noteworthy because of
      the biventricular involvement and the absence of associated congenital cardiac
      malformation. The prognosis is characterised by a high risk of severe
      cardiovascular complications.

PMID- 7646290
TI  - [Congenital pulmonary arteriovenous fistula. Apropos of 2 cases].
AB  - The authors discuss echocardiographic diagnosis and endovascular treatment of two
      different anatomical types of pulmonary arteriovenous fistula. Transoesophageal
      echocardiography in a cyanotic 3 year old boy revealed a direct right pulmonary
      artery left atrial fistula, treated by surgical ligation of the anomalous feeding
      artery. A cerebral abscess in a 22 year old man with hereditary haemorrhagic
      telangiectasia revealed pulmonary and cerebral arteriovenous malformations, which
      were both treated successfully by embolization. The value of echography is the
      demonstration of the right to left shunt at pulmonary level and, in some cases,
      the direct visualization of the arteriovenous malformation. Embolization should
      be considered as the therapeutic method of choice in all pulmonary arteriovenous
      fistula, except for direct pulmonary artery left atrial fistula.

PMID- 7646291
TI  - [Antiphospholipid syndrome in children. Apropos of a case].
AB  - The authors report the case of a 10 year old child who presented with an
      uncomplicated deep venous thrombosis associated with an antiphospholipid
      syndrome. The diagnosis was established by the finding of spontaneous
      prolongation of the activated cephalin time, the finding of a lupus-like antibody
      and an anti-cardiolipin antibody. The clinical outcome was good with oral
      anticoagulants but a recurrence was observed when they were stopped. The authors
      discuss the question of the duration of preventive therapy.

PMID- 7646292
TI  - [Repeated thrombolysis and difficulties in treatment with antivitamin K in an
      infant with mitral valve prosthesis].
AB  - The finding of cardiac failure in a neonate led to the diagnosis of congenital
      mitral regurgitation complicating dystrophic valves. After failed surgical
      valvuloplasty, the child underwent mitral valve replacement with a Saint-Jude
      medical prosthesis at the age of 4 months. The child developed four episodes of
      prosthetic valve thrombosis in the two years that followed. The first was treated
      surgically but the three others were treated by thrombolysis associating
      plasminogen tissue activator and urokinase. All but one of the thromboses
      occurred in a context of recent destabilisation of oral anticoagulant therapy
      despite the initiation of heparin. Repeat thrombolysis was successfully
      undertaken, thereby widening the indications of this type of treatment in the
      infant. This case also underlines the difficulties of oral anticoagulants in
      infants.

PMID- 7646293
TI  - [Stenoses of the supra-aortic trunks associated with aortic supravalvular
      stenosis in a 3-year-old girl. Long-term surgical result].
AB  - Supravalvular aortic stenosis may be associated with arterial lesions. This
      condition is rare and its natural history is not well known. The authors report
      the case of a child operated in 1981 for supravalvular aortic stenosis and
      stenoses of the supraaortic vessels. The operation consisted of enlarging the
      ascending aorta with a patch and resection-reimplantation of both carotids
      without interposition of prosthetic material. Twelve years later, the
      haemodynamic result was the same as that of the postoperative control. This case
      tends to prove the low evolutive potential of this condition and the long term
      benefits of this surgical technique.

PMID- 7646294
TI  - [Myocardial infarction in non-menopausal women. Coronary lesions and prognosis].
AB  - Between 1977 and 1990, 64 premenopausal women, under 50 years of age (42 +/- 5.6
      years), were admitted for typical acute myocardial infarction with pathological Q
      waves. Twenty one patients had attempted myocardial revascularisation either by
      intravenous thrombolysis or primary angioplasty (n = 3). All patients underwent
      coronary angiography with selective left ventriculography during their hospital
      admission. This group of 64 women was characterised by the association of
      coronary risk factors (2.8 per patient): smoking (89%), hyperlipidaemia (67%),
      diabetes (45%) and oral contraception (35%). Coronary angiography showed single
      vessel occlusion in 86% of patients receiving oral contraception, multiple vessel
      disease in 36.5% and single or double vessel disease in 31.7% of the other
      patients. There were 3 deaths during the hospital period (4.6%), 12 cases of left
      ventricular failure, 2 ventricular aneurysms, 2 operated ischaemic mitral
      regurgitations and 9 recurrences of pain treated by angioplasty. During follow-up
      (36.5 +/- 4 months), 22 patients were readmitted to hospital and there were 3
      further deaths, 12 cases of persistent cardiac failure, 10 cases of latent
      ventricular dysfunction and 9 ischaemic reoccurrences treated by angioplasty or
      surgery. The results in this group of patients suffering from myocardial
      infarction at an unusually early age for women showed that although the mortality
      was similar to that observed in men of the same age (9%) there was a very high
      morbidity and a high risk of cardiac failure. The prognosis of myocardial
      infarction in women, though better than 10 years ago, should improve with
      immediate revascularisation, the correction of cardiovascular risk factors and
      the rapid application of all techniques of modern cardiology.

PMID- 7646295
TI  - [Efficacy and safety of thrombolytic therapy in the elderly with severe pulmonary
      embolism].
AB  - Thrombolytic therapy leads to more rapid dissolution of thrombi in severe
      pulmonary embolism than conventional heparin therapy but is considered with much
      reserve in elderly patients because of the risk of haemorrhage, which is thought
      to be potentially greater in these subjects. The object of this study was to
      assess the efficacy and safety of thrombolytic therapy in patients over 70 years
      of age with severe pulmonary embolism, compared with patients under 70 years of
      age with the same condition. Eighty-nine patients with severe pulmonary embolism
      (Miller score > 17/34) were prescribed thrombolytic therapy in the absence of a
      contraindication without taking age into consideration. Fifty-three were under 70
      years of age (54 +/- 15; range: 18 to 70 years) and 36 were over 70 years of age
      (78 +/- 5; range: 71 to 88 years). Apart from age, there was no difference in the
      clinical presentation of the two groups. Thrombolytic therapy was initiated with
      streptokinase 100,000 IU/hr for twelve hours after an initial bolus of 250,000 IU
      or with urokinase or plasminogen tissue activator in cases with a
      contraindication to streptokinase. An uncomplicated course was observed in the
      same percentage of cases in the two groups. The Miller score and mean pulmonary
      pressures fell in the same way in the two groups. Three patients died during the
      hospital period, two aged under 70 (3.7%) and one over 7 years of age (2.7%).
      Major bleeding occurred in 3 subjects under 70 (5.6%) and 5 subjects over 70
      (13.8%) (p = 0.29).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7646296
TI  - [Identification of hibernating myocardium using 99m sestamibi tomoscintigraphy at
      rest].
AB  - The aim of this study was to assess the value of resting 99m Tc-Sestamibi
      scintigraphy for the detection of hibernating myocardium in zones of contractile
      dysfunction. Based on a series of 25 patients, 27 segments of supposedly
      hibernating myocardium were identified. All these segments corresponded to left
      ventricular wall motion abnormalities confirmed by contrast angiography and were
      perfused by a stenosed coronary artery: none of these zones were infarcted.
      Before revascularisation, comparison of the results of ventriculography and
      scintigraphy showed a correlation (p < 0.001) between the severity of regional
      contractile dysfunction appreciated by the center line method and the degree of
      myocardial hypofixation of 99m Tc MIBI. Three months after revascularisation,
      improvement of regional wall motion, assessed by control contrast angiography,
      was observed in 21 of the 27 segments studied (78%). Of these 21 segments, the
      viability of which was confirmed, 13 had a non-transmural uptake defect and 8
      were normal on pre-revascularisation scintigraphy. The 6 segments without
      improvement at the 3 month control, had a transmural uptake defect on
      scintigraphy in 67% of cases. The authors concluded that when a residual uptake
      defect of 99m Tc sestamibi is present, viable myocardium may also be present.

PMID- 7646297
TI  - [Does mitral insufficiency prevent spontaneous contrast phenomenon and formation
      of thrombi in the left atrium?].
AB  - The aim of this study was to assess the influence of mitral regurgitation on the
      prevalence of left atrial spontaneous echo contrast and thrombosis in 2,180
      consecutive patients undergoing transthoracic and transoesophageal
      echocardiography. Two groups of patients were defined according to the absence
      (group I) or presence (group II) of grades 3 or 4 mitral regurgitation quantified
      by transoesophageal echocardiography. Group II was associated with a
      statistically significant lower frequency of spontaneous echo contrast (0.6 vs
      11.2%; p < 0.0001), left atrial thrombosis (0.6 vs 4.2%; p < 0.03), ischaemic
      cerebrovascular accidents (1.2 vs 21%; p < 0.0001), transient ischaemic attacks
      (0 vs 12%; p < 0.0001) and systemic embolism (0 vs 4.6%; p < 0.01). Conversely,
      the prevalence of atrial fibrillation was higher in group II (28 vs 19%; p <
      0.01) and there were more patients with left atrial dimensions > or = 5.5 cm (16
      vs 6.7%; p < 0.0001). When mitral stenosis and valve prosthesis were excluded,
      there were no cases of spontaneous echo contrast (8.3 vs 0%; p < 0.001) or left
      atrial thrombosis (2.9 vs 0%; p < 0.05) in the group with grades 3 or 4 mitral
      regurgitation. The phenomenon of left atrial spontaneous echo contrast and/or
      thrombosis is rare in patients with grade 3 or 4 in native mitral valve
      regurgitation and explains the low incidence of systemic embolism in these cases.

PMID- 7646298
TI  - [Changes in operative risk and its predictive factors in coronary surgery].
AB  - The operative risk of coronary bypass surgery has been reported by many surgical
      groups. Although the 1970's were characterised by a progressive decline in this
      risk related to improved surgical techniques and myocardial protection, the
      following decade saw a new rise in operative mortality. In order to assess this
      problem, the authors undertook a review of 3,632 consecutive cases of coronary
      bypass surgery (without any other procedure) from 1982 to 1991. The operative
      risk increased from 2% in 1982 to 7.7% in 1989 and was related to an increase in
      patients' age, in left ventricular dysfunction and in the number of emergency and
      redux operation. The development of interventricular cardiology in the last few
      years (angioplasty for double or triple vessel disease, thrombolysis in the acute
      phase of myocardial infarction) has also increased the number of patients
      operated as emergencies with a high operative risk. The reduction of the
      operative risk observed since 1989 is due to better overall management (pre, per
      and postoperative), especially of the high risk patients (patients over 70 years
      of age, women, left ventricular dysfunction, left main coronary stenosis,
      emergencies, reoperation). Although many variables indicating extramortality were
      found to be statistically significant (p < 0.05) on univariate analysis,
      multivariate analysis by two year periods showed the following independent
      prognostic factors of operative mortality: persistence of the concept of
      "emergency surgery" throughout the period under study and, from 1986, the
      appearance of gender and NYHA Class; and, from 1988, the factor "reoperation"
      with different values of "p" according to the years under consideration.

PMID- 7646299
TI  - [Immediate and long-term results of replacement of the ascending aorta in
      aneurysm or dissection].
AB  - Between April 1974 and November 1992, 181 patients were operated for aneurysm
      (106) or dissection (75) of the ascending aorta. Eighty patients had replacement
      with a valvular conduit with reimplantation of the coronary arteries (Bentall
      procedure), 48 had aortic valve replacement with replacement of the supra
      coronary ascending aorta and 53 underwent isolated replacement of the ascending
      aorta. Twenty-nine patients (16%) died in the postoperative period, mainly of
      myocardial or neurological complications. Univariate statistical analysis
      completed by logistic regression analysis revealed the following predictive
      factors of early death: NYHA Stage IV, angina, reoperation for haemorrhage or
      tamponade (all < 0.05). All surviving patients were followed up (total follow-up:
      788 years; mean: 62 months; range: 1 to 181 months). There were 20 secondary
      deaths, 40% of which were related to complications of aortic valve replacement.
      The 5 and 9 year survivals were 76 and 70% respectively, perioperative mortality
      included, and 89% of patients were in NYHA functional Stage I. Analysis of
      survival data did not reveal any predictive factor of secondary death. Eight
      patients were reoperated at long-term. The operative mortality of replacement of
      the ascending aorta remains high, especially in cases of dissection. The long
      term results seem excellent with a low reoperation rate. Late mortality seems
      mainly due to complications of aortic valve replacement.

PMID- 7646301
TI  - [Ischemic preconditioning: concept of endogenous myocardial protection].
AB  - Preconditioning is a temporary tolerance to ischaemia acquired by the myocardium
      after a short period of ischaemia. It results in the limitation of the infarct
      size induced by prolonged coronary occlusion. The mechanism of this
      cytoprotection remains poorly understood. The A1 adenosine receptors, the ATP
      sensitive potassium channels and protein-kinase C seem to play prominent roles.
      The effects of preconditioning on the complications of ischaemia/reperfusion such
      as myocardial stunning, ventricular arrhythmias or decreased coronary reserve are
      not well known. Several studies suggest that the cytoprotection resulting from
      preconditioning could be applied to human myocardium and constitute a preventive
      anti-ischaemic therapy during coronary angioplasty, cardiac surgery or the
      conservation of transplant grafts.

PMID- 7646302
TI  - [Traumatic tricuspid insufficiency. Apropos of 2 cases].
AB  - The authors report two cases of tricuspid regurgitation by a ruptured anterior
      papillary muscle secondary to non-penetrating thoracic trauma. In the presence of
      suggestive clinical and electrocardiographic abnormalities (systolic murmur,
      right heart failure, right bundle branch block), echocardiography confirmed the
      tricuspid regurgitation, showed its mechanism and excluded any other intracardiac
      lesions. Tricuspid annuloplasty was performed in both cases because of the
      persistence of failure or degradation of the patient's clinical condition.
      Peroperative echocardiography was used to judge the quality of the surgical
      repair in both cases. Traumatic tricuspid regurgitation is a rare condition and
      the diagnosis is often delayed. Echocardiography is the investigation of choice
      and guides treatment which is essentially valvular repair in symptomatic
      patients.

PMID- 7646300
TI  - [Value of end diastolic pulmonary venous flow in the estimation of left
      ventricular diastolic pressure].
AB  - The aim of this study was to analyse the possible relationship between inversion
      of the end diastolic wave of pulmonary venous flow (Avp) recorded by
      transoesophageal echocardiography in the left superior pulmonary vein and left
      ventricular end-diastolic pressures (LVEDP) at cardiac catheterisation. In this
      series of patients, there was a poor correlation between the E/A ratio of
      transmitral blood flow and LVEDP. On the other hand, there was a better
      correlation between LVEDP and the difference of duration of the end diastolic Avp
      wave and the A wave of mitral flow. An even better correlation was found between
      LVEDP with respect to the contribution of atrial systole and the difference of
      duration Avp-A. When the pressure due to atrial contraction exceeds 15 mmHg, the
      difference between the durations of pulmonary and mitral A waves increases.
      Therefore, when the duration of the end diastolic Avp is greater than that of the
      mitral A wave, a LVEDP of over 15 mmHg may be predicted with a sensitivity of 88%
      and a specificity of 74%.

PMID- 7646303
TI  - [Corynebacterium diphtheriae endocarditis complicated by septic arthritis and
      cerebral abscess].
AB  - The authors report a rare case of the mitis type Corynebacterium diphteriae
      endocarditis on a prosthetic valve complicated by septic arthritis and cerebral
      abscess. The authors underline the importance of regular transoesophageal
      echocardiographic control and underline the diagnostic value of ultrafast
      computed tomography for the diagnosis of aortic annular and interventricular
      septal abscesses in patients with mechanical prosthetic valves.

PMID- 7646304
TI  - [Left anterior hemiblock induced by exertion, caused by diagonal arterial
      stenosis: apropos of a case].
AB  - The authors report the case of a patient who developed left anterior hemiblock
      and ST segment depression during exercise testing which regressed during the
      recovery period. Coronary angiography showed severe stenosis of the diagonal
      artery. This conduction defect did not recur after effective angioplasty of the
      stenosed artery, reflecting the ischaemic nature of this abnormality.

PMID- 7646305
TI  - [Sodium and left ventricular hypertrophy in patients with hypertension].
AB  - Dietary sodium is an environmental factor capable of amplifying or limiting the
      consequences of hypertension on the heart. In a given population of hypertensive
      subjects, recent clinical trials have shown a positive relationship between
      sodium intake and the degree of left ventricular hypertrophy, independently of
      the value of blood pressure and body weight. In addition, dietary sodium could
      play a role in modulating the myocardial response to a decrease in blood pressure
      by antihypertensive therapy. The logical consequence of these observations is to
      try and prove the possible advantages of restricting dietary sodium in reducing
      the blood pressure and reversing left ventricular hypertrophy. With this in mind,
      the evaluation of dietary sodium excretion is certainly an element to take into
      account in the initial evaluation and also the follow-up of hypertensive subjects
      and of the effects of antihypertensive therapy.

PMID- 7646306
TI  - [Relation between cardiac hypertrophy and changes in the large arterial trunks.
      Role of the renin-angiotensin system].
AB  - The raised mean arterial pressure observed in hypertension increases the stress
      on the walls of large arteries by increasing the mechanical forces to which they
      are submitted. Cardiac and arterial wall hypertrophy seem to be adaptive
      mechanisms tending to reduce the stress in each musculo-elastic unit of the
      cardiovascular system. However, this adaptation only partially explains the
      development of cardiovascular hypertrophy. Cardiovascular changes are sometimes
      observed before the increase in blood pressure, as in normotensive children of
      hypertensive parents. Moreover, a dissociation has been shown between the
      antihypertensive effects of different antihypertensive agents. For the same
      reduction in mean arterial pressure, some drugs are associated with a greater
      regression in these changes than others. At present, it is acknowledged that
      other factors than mean arterial pressure may cause these changes. For example,
      the pulse pressure is a major factor, independent of mean arterial pressure, in
      developing cardiovascular hypertrophy. The activation of hormonal systems,
      especially the angiotensin converting enzyme system, influences cardiovascular
      structure. Therefore, hyperactivity of the renin-angiotensin system may stimulate
      the growth factor responsible for cardiac and arterial hypertrophy.

PMID- 7646307
TI  - [Genetics and left ventricular hypertrophy].

PMID- 7646308
TI  - [Detection of left ventricular hypertrophy in arterial hypertension].
AB  - Left ventricular hypertrophy is an important risk factor in hypertension and the
      results of the HYCAR study confirm that it is possible to treat this risk factor
      independently of an action on the blood pressure. Should systematic
      echocardiography be performed in every hypertensive patient to diagnose left
      ventricular hypertrophy and follow up its outcome with treatment? This attitude
      seems to be premature for two reasons. Firstly, echocardiography, though much
      more sensitive than electrocardiography for diagnosing left ventricular
      hypertrophy, has a number of limitations. Good recordings cannot be obtained in
      all patients; even under the best conditions of reproducibility, the measurement
      of left ventricular mass is not excellent and does not allow reliable individual
      follow-up of treatment; even the criteria of left ventricular hypertrophy used at
      present are open to criticism. Secondly, it remains to be shown whether the
      reversibility of left ventricular hypertrophy, independently of lowering the
      blood pressure, improves the prognosis of the hypertensive patient. The intensive
      research into this problem, further stimulated by the encouraging results of the
      HYCAR study, should help define the role and value of echocardiography in the
      future management of hypertension.

PMID- 7646309
TI  - Experimental evidence for effects of ramipril on cardiac and vascular hypertrophy
      beyond blood pressure reduction.
AB  - In renal hypertensive rats with pressure overload left ventricular hypertrophy
      the angiotensin converting enzyme inhibitor ramipril, given in a high blood
      pressure lowering dose as well as in a low, non-antihypertensive dose, prevented
      and regressed left ventricular hypertrophy. These beneficial effects were
      abolished by coadministration of the specific bradykinin receptor antagonist (HOE
      140) in the prevention--but not in the regression studies. Vascular function of
      rats with pressure overload left ventricular hypertrophy was impaired, whereas
      treated animals showed a reversal to normal. The angiotensin II subtype AT1
      receptor antagonist, losartan, was barely active in the prevention, however
      markedly active in the regression of left ventricular hypertrophy. From these
      experimental studies in rats with pressure overload left ventricular hypertrophy
      and vascular dysfunction we conclude that inhibition of bradykinin degradation
      induced by ramipril may contribute to the antihypertrophic action during the
      prevention phase, whereas attenuation of angiotensin II formation may be more
      important during the regression period. In another model, the spontaneously
      hypertensive rat (SHR and stroke prone SHR)--a non-renal hypertensive model-
      cardiac left ventricular hypertrophy could be reduced by chronic high-dose
      ramipril treatment in prevention and regression studies, whereas the low dose
      regimen only reduced left ventricular hypertrophy in the regression experiments.
      In addition, both doses improved the myocardial capillary supply to the heart
      leading to improved function and metabolism. In comparison, vascular hypertrophy
      of the mesenteric artery could only be prevented by early-onset high dose
      treatment with the angiotensin converting enzyme inhibitor but not once
      hypertrophy has been established.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7646310
TI  - [Remission of left ventricular hypertrophy with ramipril independently of blood
      pressure changes: the HYCAR study (cardiac hypertrophy and ramipril)].
AB  - Most studies of the regression of left ventricular hypertrophy by
      antihypertensive treatment have methodological weaknesses and have not shown if
      regression of left ventricular hypertrophy can be obtained independently of blood
      pressure reduction. In the HYCAR study, after an inclusion phase of 4 to 6 weeks
      on furosemide (20 mg/day), 115 patients with left ventricular hypertrophy were
      randomised in a double blind manner to placebo group (N = 40), ramipril, 1.25
      mg/day, (N = 38) or 5 mg/day (N = 37) for a period of 6 months. Furosemide was
      continued during the double blind treatment period. Echocardiography and
      ambulatory blood pressure monitoring were performed just before the randomisation
      and at 6 months. At the end of the study, there was no significant difference
      between the casual and ambulatory blood pressure changes. Expressed in g/m, the
      left ventricular mass index decreased significantly with respect to placebo in
      the ramipril 5 mg group (-12.2 +/- 3.9 versus +5.5 +/- 4.3 g/m2, p = 0.003) and
      in the 1.25 mg group (-7.5 +/- 4.6 g/m2, p = 0.04). The reduction in left
      ventricular mass index expressed in g/m2 was significant in the 5 mg ramipril (p
      = 0.008) but not in the 1.25 mg ramipril group (p = 0.06).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7646311
TI  - [Ramipril and cardiac and renal angiotensin converting enzyme].
AB  - The role of the angiotensin converting enzyme (ACE) in the regulation of local
      synthesis of angiotensin II has not been clearly defined. The authors
      investigated the local factors which might orientate the effects of ACE
      inhibitors to particular organs in the Wistar rat. The in vivo study of the
      effects of low doses of ramipril on the myocardium showed that cardiac ACE was
      significantly inhibited by the non-antihypertensive dose of 0.01 mg/kg whereas
      the inhibition only occurred from doses higher than 0.1 mg/kg in the other
      tissues studied. In the kidney: the affinity of 3H-ramiprilate for the brush
      borders of the proximal tubular cells was increased by high concentrations of
      chloride ions as observed in the renal parenchyma, the presence of esterases
      makes local activation of ramipril (diester) into ramiprilate (active diacid)
      possible, prolonged treatment with ramipril leads to a lowering of the
      concentration of ACE in the brush border of the proximal tubular cells, verified
      after the elimination of the ACE inhibitor fixed on the tissue. These data
      indicate that the myocardium and the kidney could be privileged targets of the
      action of ramipril.

PMID- 7646312
TI  - [Is reversal of left ventricular hypertrophy a priority in patients with
      hypertension?].
AB  - Left ventricular hypertrophy is frequent in hypertension although there is no
      close correlation between the level of blood pressure and the cardiac mass. The
      HYCAR study has shown a dissociation in the reversibility of left ventricular
      hypertrophy: ramipril at doses of 1.25 or 5 mg per day reduces left ventricular
      mass independently of its effects on the blood pressure. Nevertheless, it remains
      to be shown by a prospective study that the reduction of the blood pressure and
      the cardiac mass have additional benefits in the prevention of coronary artery
      disease in hypertensive subjects. In the meantime, two points resume the
      objectives of treatment of hypertension with respect to left ventricular
      hypertrophy and coronary risk. Firstly, prevention of left ventricular
      hypertrophy is better than its cure. Early prevention is based on accurate
      measurement and interpretation of the blood pressure according to international
      recommendations. Prevention necessitates good control of the blood pressure and
      it would appear to be particularly effective in patients who respond well to
      angiotensin converting enzyme inhibitors. Secondly, when left ventricular
      hypertrophy is present, it is possible to reduce the left ventricular mass:
      however, it remains to be seen whether this is accompanied by a normalisation of
      structure and function. This requires control of the blood pressure using either
      an angiotensin converting enzyme inhibitor in good responders to this family of
      drugs or another type of antihypertensive agent. In the latter case, the
      association of a low dose of ramipril may be envisaged when left ventricular
      hypertrophy persists despite good control of the blood pressure. This hypothesis
      requires testing with an appropriate prospective therapeutic trial.

PMID- 7646313
TI  - [Physiopathology of left ventricular hypertrophy].
AB  - Left ventricular hypertrophy (LVH) is an early complication of hypertension. To a
      certain degree, this process counteracts the parietal stress induced by high
      blood pressure. Genetic factors, obesity, high salt diet and different growth
      factors, notably angiotensin II and noradrenaline, can also predispose to
      hypertrophic cardiomyopathy. Left ventricular mass is increased on
      echocardiography in about 20% of hypertensive subjects. LVH is initially
      associated with a change in myocardial diastolic function and later with abnormal
      systolic function. It is a major risk factor, a cause of cardiac failure,
      reduction in coronary reserve and of ventricular arrhythmias. Treatment of
      hypertension is associated with regression of LVH and preservation or improvement
      in myocardial diastolic and systolic functions. The decrease in left ventricular
      mass could reduce the incidence of cardiovascular complications in hypertension.

PMID- 7646314
TI  - Purification and characterization of ferritin from Campylobacter jejuni.
AB  - We purified an iron-containing protein from Campylobacter jejuni using
      ultracentrifugation and ion-exchange chromatography. Electron microscopy of this
      protein revealed circular particles with a diameter of 11.5 nm and a central core
      with a diameter of 5.5 nm. The protein was composed of a single peptide of 21 kDa
      and did not serologically cross-react with horse spleen ferritin. The UV-visible
      spectrum of the protein showed no absorption peaks in the visible region,
      indicating that little or no heme is bound. The ratio of Fe:phosphate of C.
      jejuni ferritin was 1.5:1. From these morphological and chemical examinations, we
      concluded that the C. jejuni purified protein is a ferritin of the same class as
      that of Helicobacter pylori and Bacteroides fragilis and differs from the heme
      containing bacterioferritin of Escherichia coli. The 30 N-terminal amino acids
      were sequenced and were found to resemble the sequences of other ferritins
      strongly (H. pylori ferritin, 73% identity; B. fragilis ferritin, 50% identity;
      E. coli gene-165 product, 50% identity), and to a lesser degree,
      bacterioferritins (E. coli bacterioferritin, 26% identity; Azotobacter
      vinelandii, 26% identity; horse spleen ferritin 30% identity). Proteins that
      cross-reacted with antiserum against the ferritin of C. jejuni were found in
      other Campylobacter species and in H. pylori, but not in Vibrio, E. coli, or
      Pseudomonas aeruginosa.

PMID- 7646315
TI  - A new obligately chemolithoautotrophic, nitrite-oxidizing bacterium, Nitrospira
      moscoviensis sp. nov. and its phylogenetic relationship.
AB  - A gram-negative, non-motile, non-marine, nitrite-oxidizing bacterium was isolated
      from an enrichment culture initiated with a sample from a partially corroded area
      of an iron pipe of a heating system in Moscow, Russia. The cells were 0.9-2.2
      microns x 0.2-0.4 microns in size. They were helical- to vibroid-shaped and often
      formed spirals with up to three turns 0.8-1.0 micron in width. The organism
      possessed an enlarged periplasmic space and lacked intracytoplasmic membranes and
      carboxysomes. The cells tended to excrete extracellular polymers, forming
      aggregates. The bacterium grew optimally at 39 degrees C and pH 7.6-8.0 in a
      mineral medium with nitrite as sole energy source and carbon dioxide as sole
      carbon source. The optimal nitrite concentration was 0.35 mM. Nitrite was
      oxidized to nitrate stoichiometrically. The doubling time was 12 h in a mineral
      medium with 7.5 mM nitrite. The cell yield was low; only 0.9 mg protein/l was
      formed during oxidation of 7.5 mM nitrite. Under anoxic conditions, hydrogen was
      used as electron donor with nitrate as electron acceptor. Organic matter (yeast
      extract, meat extract, peptone) supported neither mixotrophic nor heterotrophic
      growth. At concentrations as low as 0.75 g organic matter/l or higher, growth of
      nitrite-oxidizing cells was inhibited. The cells contained cytochromes of the b-
      and c-type. The G+C content of DNA was 56.9 +/- 0.4 mol%. The
      chemolithoautotrophic nitrite-oxidizer differed from the terrestrial members of
      the genus Nitrobacter with regard to morphology and substrate range and equaled
      Nitrospira marina in both characteristics. The isolated bacterium is designated
      as a new species of the genus Nitrospira.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7646316
TI  - Glutamate excretion in Escherichia coli: dependency on the relA and spoT
      genotype.
AB  - Glutamate excretion due to amino acid starvation was investigated in "stringent"
      and "relaxed" strains of Escherichia coli. The observed excretion process is relA
      dependent, carrier-mediated, and glutamate-specific. After induction, excretion
      was detected within less than 2 min and continued for more than 5 h with a rate
      of 7-10 nmol (mg dry weight)-1 min-1. Using carbonyl cyanide m
      chlorophenylhydrazone or polymyxin B nonapeptide, together with valinomycin, it
      was shown that glutamate excretion is driven by the membrane potential.

PMID- 7646317
TI  - Succinate decarboxylation by Propionigenium maris sp. nov., a new anaerobic
      bacterium from an estuarine sediment.
AB  - Enrichments on succinate plus yeast extract under anoxic conditions from
      intertidal mud-flat sediments yielded cultures dominated by oval to round-ended
      rod-shaped cells. Strain 10succ1, obtained in pure culture, was characterized in
      detail. The non-motile cells possessed a gram-negative cell wall and did not form
      spores. Carbohydrates were fermented to formate, acetate, ethanol, and lactate.
      Succinate was decarboxylated to propionate. Other organic and amino acids were
      variously fermented to formate, acetate, propionate, and butyrate. Sulfur,
      sulfate, thiosulfate, and nitrate were not used as electron acceptors. Growth
      required the presence of yeast extract and at least 5 g/l NaCl, and was possible
      only in the absence of oxygen. No cytochromes were detected. The DNA base ratio
      was 40 mol% G + C. Phylogenetically, strain 10succ1 is closely related to
      Propionigenium modestum, as revealed by 16S rDNA analysis, but is physiologically
      distinct. Accordingly, strain 10succ1 (DSM 9537) is described as the type strain
      of a new species of the genus Propionigenium, P. maris sp. nov.

PMID- 7646318
TI  - Purification and characterization of 4-hydroxybenzoate 3-hydroxylase from a
      Klebsiella pneumoniae mutant strain.
AB  - Unlike the parent wild-type strain, the Klebsiella pneumoniae mutant strain MAO4
      has a 4-HBA+ phenotype. The capacity of this mutant to take up and metabolize 4
      hydroxybenzoate (4-HBA) relies on the expression of a permease and an NADPH
      linked monooxygenase (4-HBA-3-hydroxylase). Both enzymes are normally expressed
      at basal levels, and only the presence of 4-HBA in the media enhances their
      activities. Strikingly, when the Acinetobacter calcoaceticus pobA gene encoding 4
      hydroxybenzoate-3-hydroxylase was expressed in hydroxybenzoate K. pneumoniae wild
      type, the bacteria were unable to grow on 4-HBA, suggesting that the main
      difference between the wild-type and the mutant strain is the capability of the
      latter to take up 4-HBA. 4-HBA-3-hydroxylase was purified to homogeneity by
      affinity, gel-filtration, and anion-exchange chromatography. The native enzyme,
      which appeared to be a dimer of identical subunits, had an apparent molecular
      mass of 80 kDa and a pI of 4.6. Steady-state kinetics were analyzed; the initial
      velocity patterns were consistent with a concerted substitution mechanism. The
      purified enzyme had 362 amino acid residues, and a tyrosine seemed to be involved
      in substrate activation.

PMID- 7646319
TI  - Artificial neural networks for medical classification decisions.
AB  - Neural networks are growing in popularity. However, empirically comparing them
      with traditional methods of solving medical classification decisions is not
      trivial. Following a brief description and comparison with the statistical
      technique, discriminant analysis, the methodology for comparing neural networks
      with discriminant analysis is described. The advantages and disadvantages of
      neural networks are summarized to support a conclusion that neural networks are
      beneficial and destined to proliferate. Areas of fruitful future research are
      identified.

PMID- 7646320
TI  - False-positive human immunodeficiency virus screening test related to rabies
      vaccination.

PMID- 7646321
TI  - Idiopathic granulomatous mastitis and extramammary manifestations.

PMID- 7646322
TI  - Intracytoplasmic inclusions in benign prostatic epithelium.

PMID- 7646323
TI  - Interinstitutional comparison of bladder carcinoma surgical pathology report
      adequacy. A College of American Pathologists Q-Probes Study of 7234 bladder
      biopsies and curettings in 268 institutions.
AB  - Participants in the 1992 College of American Pathologists' Q-Probes Study of
      bladder carcinoma surgical report adequacy evaluated 7234 bladder biopsies and
      curettings from 268 institutions. In over 98% of the cases evaluated, the
      histologic type was stated. In over 95%, the histologic grade was stated where
      appropriate. Of the 7234 cases studied, 2149 (29.7%) were invasive, 4498 (62.2%)
      were noninvasive, and invasiveness (presence or absence of invasion) was not
      stated for 587 (8.1%). For invasive carcinomas, there was definitive assessment
      for the presence or absence of muscularis propria in 1145 (53.3%) of 2149 cases,
      and in 67 (3.1%) of 2149 cases no muscle or muscularis was present. For
      noninvasive carcinomas, there was a definitive evaluation of the muscularis
      propria (presence or absence) in 1349 (30%) of 4498 cases.

PMID- 7646324
TI  - Evaluating lyophilized human serum preparations for suitability as proficiency
      testing materials for high-density lipoprotein cholesterol measurement.
AB  - OBJECTIVE: To evaluate the suitability of various commercial preparations for use
      by the College of American Pathologists as survey materials in assessing high
      density lipoprotein cholesterol measurement performance. DESIGN: Lyophilized
      human serum preparations from six vendors (vendors A through F) were evaluated to
      determine which material(s) best mimicked the commutability of fresh human serum.
      Two freshly collected unfrozen pools prepared from donor specimens were analyzed
      concurrently with the vendor materials to identify sources of variation and
      possible matrix bias. Each material was evaluated using 5 common precipitation
      reagents (phosphotungstate-magnesium, phosphotungstic acid, dextran sulfate [50K
      and 500K], and heparin-manganese). To evaluate how each reagent separates
      lipoproteins in each material, the lipoprotein separation patterns were profiled
      using high-pressure liquid chromatography and compared with separation patterns
      observed for the fresh human serum pools. MAIN OUTCOME MEASURES: Similarities in
      performance characteristics of vendor material(s) were compared with fresh human
      serum. RESULTS: Two of the six materials gave separation profiles for the
      lipoproteins similar to the typical patterns observed for human serum. Material
      from vendor B showed the best commutability across all of the precipitation
      reagents and had the best combination of low overall variability (10% for level 1
      and 9.4% for level 2) and minimal concentration differences among reagents.
      CONCLUSIONS: Vendor B was selected by the College of American Pathologists to
      provide materials for use in assessing performance of lipid and lipoprotein
      testing in the 1994 Comprehensive Chemistry Surveys. This study demonstrates the
      great variability that different vendor preparations introduce into the
      measurement of high-density lipoprotein cholesterol. It also emphasizes the
      effort required to evaluate the suitability of processed materials for use in
      proficiency testing.

PMID- 7646325
TI  - Practice protocol for the examination of specimens from patients with lung
      cancer. Cancer Committee. Task Force on the Examination of Specimens from
      Patients with Lung Cancer.

PMID- 7646326
TI  - Evolution beyond the shared services model of consolidated hospital clinical
      laboratories.
AB  - OBJECTIVE: To compare the operational and financial outcomes of the transition
      from shared laboratory services to a recentralized model, in a consolidated
      hospital system. SETTING: United Health Services Hospitals (Binghamton General,
      Wilson Memorial, and Ideal hospitals, New York State). INTERVENTION:
      Consolidation of hospital services and recentralization of laboratory testing to
      a single site (Wilson Memorial Hospital). MAIN OUTCOME MEASURES: Laboratory
      workload, testing efficiency, personnel and nonpersonnel expenses, analytic error
      rate, turnaround time, and proficiency-testing scores. RESULTS: The
      postintervention period (1988 to 1992) was characterized by a 51% and a 10%
      increase in the out- and inpatient workloads, respectively, with a concomitant
      24% increase in testing efficiency. The salary expenses were 26% lower, while the
      total true cost savings ranged from $1,544,000 (11.6%) to $2,500,000 (21.9%)
      compared with the shared services model. The recentralization produced decreased
      analytic error rates and improved testing turnaround time. CONCLUSIONS: The total
      costs per test have been lowered in the recentralized model. Recentralization may
      provide further true cost savings over the shared services model while
      maintaining high-quality service.

PMID- 7646328
TI  - False 'hematuria' due to bacteriuria.
AB  - OBJECTIVE: To determine the effects of bacteriuria on dipstick urinalysis for
      microhematuria. DESIGN: Selection of urine samples with dipstick readings of at
      least one plus (+) for blood, followed by microscopic examination and bacterial
      culture, from patients with signs and symptoms of urinary tract diseases.
      SETTING: A large teaching hospital in Melbourne, Australia. PATIENTS: Two hundred
      forty-six inpatients and outpatients being investigated for signs and symptoms of
      urinary tract diseases. RESULTS: Seventeen (7%) of 246 patients having within
      reference erythrocyte counts had polymicrobic cultures. One hundred nine patients
      had slight hematuria (1 x 10(7) to 6 x 10(7) cells/L). Of these, 21 bacteriuric
      patients had significantly higher dipstick findings than 88 abacteriuric patients
      (P < .005, Fisher's Exact Probability Test, two-tailed). Hydroperoxidase was
      detected in 80% of isolates (in 27 of 27 gram-negative bacilli cultures, in 6 of
      6 staphylococci cultures, and in 3 of 12 streptococci cultures) on agar medium
      and in 69% of isolates in urine. CONCLUSION: These results show that patients
      without hematuria but with bacteriuria may give a false-positive dipstick reading
      for blood.

PMID- 7646327
TI  - User interface reengineering. Innovative applications of bar coding in a clinical
      microbiology laboratory.
AB  - Some clinical laboratory departments (such as microbiology) provide extensive
      reporting of text and other data not generated by instruments that can be
      interfaced to a laboratory information system. These data are usually entered
      into the laboratory information system manually by keyboard data entry, which can
      be cumbersome and time consuming. Bar codes, which are already used in
      laboratories to facilitate rapid entry of sample-identifying information, have
      the potential to be used much more broadly as a generalizable data entry
      technique. We developed a comprehensive system that takes advantage of several
      applications of bar coding to facilitate the work of our Clinical Microbiology
      Laboratory. Central to our system is the use of bar code "scripts" to meet many
      of our complex data entry requirements. Use of these scripts is transparent to
      the laboratory information system (ie, no special "drivers" are needed) because
      data are received as if they had been generated by typing the characters on the
      keyboard. The scripts consist of bar codes that encode the series of keystrokes
      needed to give the appropriate response at the series of prompts offered by the
      laboratory information system. Both alphanumeric and other keys, including
      carriage returns and special characters, can be converted into bar codes and
      incorporated into scripts. By creating and printing these scripts in the
      laboratory using standard wordprocessing software and bar code fonts for personal
      computers, laboratorians without specialized computer training have the tools to
      substantially improve the data entry efficiency of existing data entry terminals
      for a variety of laboratory information systems.

PMID- 7646329
TI  - Clinical value of fine-needle aspiration cytology and biopsy in the evaluation of
      male infertility. A comparative study of 48 infertile patients.
AB  - OBJECTIVE: To evaluate whether fine-needle aspiration cytology of the testis can
      be considered as a diagnostic parameter in the evaluation of male infertility.
      PATIENTS AND METHODS: We studied 30 oligospermic and 18 azoospermic patients
      using 63 fine-needle aspiration samples and 57 biopsy samples obtained surgically
      (10 cases) or with a spring-loaded biopsy device (47 cases). Cytologic evaluation
      of spermatogenesis was performed by studying longitudinal segments of
      seminiferous tubules and cytocentrifuged dissociated cells. RESULTS: Comparison
      between fine-needle aspiration and the biopsy methods gave concordant results in
      72.2% of cases. Discordant findings were recorded in 10 cases (27.8%). In eight
      cases, significant maturation into spermatozoa was recognized in samples obtained
      by fine-needle aspiration only, whereas moderate to severe hypospermatogenesis or
      germ cell aplasia were demonstrated in samples obtained by the spring-loaded
      biopsy device or by open surgical biopsy. Germ cell aplasia was recognized in
      samples obtained by both methods in 75.0% of cases. Insufficient specimens were
      obtained by fine-needle aspiration and the spring-loaded biopsy device in 15.9%
      and 12.3% of cases, respectively, whereas all surgical biopsy specimens were of
      good quality. Four bleeding episodes and one case of epididymitis were observed
      after use of the spring-loaded biopsy device, but no complication was related to
      either surgical biopsy or fine-needle aspiration. CONCLUSION: The findings show
      that fine-needle aspiration cytology could represent a more reliable means of
      identifying significant numbers of the most mature germ cells.

PMID- 7646330
TI  - Virchow's node revisited. Analysis with clinicopathologic correlation of 152 fine
      needle aspiration biopsies of supraclavicular lymph nodes.
AB  - OBJECTIVE: The left supraclavicular lymph node (Virchow's node) may be involved
      by metastatic malignancies, including those of abdominal or pelvic origin. Almost
      all previous studies have been based on examination of surgically sampled tissue
      or postmortem examination. To our knowledge, there has not been a study for
      nearly 40 years addressing the metastatic pattern to the left supraclavicular
      lymph node. Furthermore, there has been no study comparing left with right
      supraclavicular lymph node metastasis or the utilization of fine-needle
      aspiration biopsy to samples these sites. DESIGN: A retrospective review of 152
      fine-needle aspiration biopsies of supraclavicular lymph nodes was performed, and
      the neoplasms were grouped into six diagnostic categories from five primary
      regions. RESULTS: The patients ranged in age from 2 years to 94 years (average,
      55 years) and consisted of 66 males and 83 females. Three patients were biopsied
      twice. Of the 152 fine-needle aspirations, 87 (57.2%) were of the left
      supraclavicular lymph node and 65 (42.8%) of the right supraclavicular lymph
      node. Of the 96 biopsies positive for malignancy, 58 (60.4%) were biopsies of the
      left and 38 (39.6%) were of the right supraclavicular lymph nodes. Sixteen of 19
      pelvic tumors and all six primary abdominal malignancies metastasized to the left
      supraclavicular lymph node. Thorax, breast, and head and neck malignancies showed
      no differences in metastatic patterns to the right and left supraclavicular lymph
      nodes. Ten patients (10.4% of positive nodes) had a diagnosis of non-Hodgkin's
      lymphoma, leukemia, or Hodgkin's disease. Six patients (7.1% of positive nodes)
      had a metastasis of unknown primary site, and 19 cases (19.8%) had acute or
      chronic inflammation; seven of the latter cases demonstrated acid-fast bacilli in
      the aspirated smears. CONCLUSIONS: Fine-needle aspiration biopsy is an excellent
      initial procedure in the workup of an enlarged supraclavicular lymph node. Our
      study confirmed that malignancies originating in the pelvis or abdomen were
      significantly more likely to metastasize to the left supraclavicular lymph node
      and that the primary site and types of malignancies that involved the left
      supraclavicular lymph node were different from those involving the right
      supraclavicular lymph node.

PMID- 7646331
TI  - The incidence of unsuspected metastases from clinically benign prostate glands
      with latent prostate carcinoma.
AB  - OBJECTIVE: To determine how many latent prostate gland carcinomas (unsuspected
      carcinomas in clinically benign prostate glands) metastasize. DESIGN: The
      prostate glands and the pelvic and paraaortic lymph nodes were removed at autopsy
      from 209 consecutive patients with clinically benign prostate glands. The
      prostate glands were completely sectioned and examined microscopically using full
      cross sections. Pelvic and para-aortic lymph nodes were identified and examined
      microscopically for metastases. RESULTS: Seventy-nine (38%) of the prostate
      glands had latent prostate carcinomas. None of the pelvic or paraaortic lymph
      nodes contained metastases. CONCLUSION: This study suggests that few latent
      prostate-gland carcinomas metastasize.

PMID- 7646332
TI  - Calbindin-D28k in subsets of medulloblastomas and in the human medulloblastoma
      cell line D283 Med.
AB  - OBJECTIVE: To evaluate the antigenic expression of calbindin-D28k in surgically
      resected cerebellar medulloblastomas and the human medulloblastoma cell line D283
      Med in relation to glial neoplasms, the human glioblastoma (U-251 MG) and rat
      glioma (C-6) cell lines, and other primary and metastatic brain tumors. DESIGN:
      Immunohistochemical staining was performed using an antiserum and a monoclonal
      antibody against calbindin-D28k on (1) formalin-fixed, paraffin-embedded human,
      predominantly posterior fossa, brain tumor specimens (49 medulloblastomas, 59
      glial and mesenchymal primary central nervous system tumors, 1 posterior fossa
      rhabdoid tumor, and 34 metastatic tumors); (2) formalin-70% alcohol-, or Bouin's
      fixed tumor cell lines (D283 Med, U-251 MG, and C-6) maintained in a three
      dimensional gelatin foam (Gelfoam matrix) system, with or without treatment with
      dibutyryl cyclic adenosine monophosphate; and (3) formalin-fixed, paraffin
      embedded C-6 glioma cells transplanted intracerebrally to rats. RESULTS:
      Calbindin-D28k immunohistochemical staining was detected in 20 of 49 cerebellar
      medulloblastomas and in cells of the human medulloblastoma cell line D283 Med
      grown in gelatin Gelfoam matrices, with or without treatment with dibutyryl
      cyclic adenosine monophosphate. In surgical resection specimens, calbindin-D28k
      reactivity was evident in populations of poorly differentiated cells of classic
      (non-nodular) medulloblastomas (16/20) and in mature Purkinje neuronlike
      phenotypes in medulloblastomas with ganglion cells (4/6) but was absent in
      desmoplastic medulloblastomas, including in areas of neoplastic neuritogenesis
      ("pale islands") (0/23). Calbindin-D28k staining was also present in D283 Med
      explants for up to 29 days in vitro. Reactivity was more widespread in dibutyryl
      cyclic adenosine monophosphate-treated cultures, coinciding with neuronal
      morphologic alterations of cultured cells. Focal calbindin-D28k stainig was
      present in neural-like cells of an embryonal cerebellar tumor with divergent
      mesenchymal, epithelial, and neuroectodermal/neuroendocrine differentiation
      suggestive of a malignant rhabdoid tumor. No calbindin-D28k staining was obtained
      in primary glial and mesenchymal (intra- and extra-axial) brain tumors (0/59), in
      explants of human glioblastoma cell line U-251 MG, or in the rat glioma line C-6
      maintained in Gelfoam matrices or transplanted intracerebrally. Among 34
      epithelial and mesenchymal tumors metastatic to the posterior fossa, only
      subpopulations of cells in two small-cell (neuroendocrine) carcinomas originating
      in the lung were calbindin positive. CONCLUSION: Calbindin-D28k expression in
      classic medulloblastomas, medulloblastomas with ganglion cells, and in the human
      medulloblastoma cell line D283 Med (which was derived from a metastatic classic
      medulloblastoma) suggests a phenotypic kinship between subsets of this tumor and
      neuronal progeny of the ventricular neuroepithelium, thus conferring additional
      support for its neuroblastic nature.

PMID- 7646333
TI  - Asynchronous pituitary adenomas with differing morphology.
AB  - Recurrent pituitary tumors can sometimes pose a diagnostic and therapeutic
      challenge. We report a case of a 43-year-old man who presented twice, 13 years
      apart, with pituitary adenoma marked by headaches, visual impairment, and no
      signs of endocrinologic abnormality. At initial presentation computed tomographic
      scan documented a pituitary mass eroding the sellar floor, with suprasellar and
      parasellar extension. The patient underwent transsphenoidal surgery and the tumor
      was classified as a silent corticotroph adenoma, subtype 2. Thirteen years later,
      clinical symptoms of a destructive pituitary mass reappeared. This time, the
      adenoma revealed typical ultrastructural features of an oncocytoma; it had a
      different immunocytochemical profile from the first tumor. Given these striking
      morphologic differences, we consider the two adenomas to represent asynchronous,
      de novo formations. We conclude that the recurrence of a resected pituitary tumor
      may also represent a metachronous development of two distinct pituitary adenomas.

PMID- 7646334
TI  - Functional hyposplenism due to a primary epithelioid hemangioendothelioma of the
      spleen.
AB  - We present a unique case of functional hyposplenism due to massive involvement of
      the spleen by a rare tumor, an epithelioid hemangioendothelioma, in a 9-year-old
      girl. To our knowledge, three previous cases of this disorder involving the
      spleen have been reported, but this is the first associated with functional
      hyposplenism.

PMID- 7646335
TI  - Primary cutaneous angiotropic large-cell lymphoma in a patient with acquired
      immunodeficiency syndrome.
AB  - Patients with acquired immunodeficiency syndrome are at increased risk of
      developing malignant lymphoma, particularly of the large noncleaved,
      immunoblastic, and small noncleaved cell types. Angiotropic large-cell lymphoma,
      a relatively rare high-grade lymphoma, has not previously been described in the
      setting of acquired immunodeficiency syndrome. Because angiotropic large-cell
      lymphoma most commonly involves the skin and central nervous system, and because
      of its relative rarity, its presentation in the skin of a patient with acquired
      immunodeficiency syndrome may pose a diagnostic dilemma.

PMID- 7646336
TI  - The role of interferon beta in human cytomegalovirus-mediated inhibition of HLA
      DR induction on endothelial cells.
AB  - Human cytomegalovirus (HCMV), a member of the virus family Herpesviridae that is
      associated with extensive worldwide morbidity and mortality in immunocompromised
      hosts, inhibits interferon-gamma (IFN gamma)-mediated induction of human
      leukocyte antigen (HLA) class II antigens on endothelial cells. In this study,
      the ability of HCMV-infected endothelial cells to synthesize interferon-beta (IFN
      beta), and the role of IFN beta in HCMV-mediated inhibition of HLA class II
      induction, was investigated. As determined by an encephalomyocarditis virus
      protection assay, HCMV-infected endothelial cell culture supernatants contained
      240 IU/ml of IFN type I activity, of which 99.9% was IFN beta, as compared to the
      absence of IFN beta in mock-infected culture supernatants. UV-irradiated
      supernatants from HCMV-infected cultures inhibited induction of HLA class II in
      noninfected cultures by 24%. This inhibition could be abolished with 500 NU/ml of
      anti-IFN beta antibody. Addition of anti-IFN beta antibody directly to HCMV
      infected cultures mitigated but did not abolish HLA class II antigen inhibition.
      Dual immunohistochemistry for HCMV and HLA DR demonstrated that infected cells,
      in contrast to noninfected cells, were rarely induced to express HLA class II
      even in the presence of anti-IFN beta antibody. These findings suggest that HCMV
      inhibits induction of HLA class II antigens by IFN beta dependent and independent
      mechanisms.

PMID- 7646337
TI  - Japanese encephalitis virus infection of mouse cell lines: ability to prime mice
      for generation of virus specific cytotoxic T lymphocytes and differences in CTL
      recognisable viral determinants.
AB  - Ten different mouse cell lines were examined for Japanese encephalitis virus
      (JEV) infection in vitro and then tested for their ability to generate virus
      specific cytotoxic T lymphocytes (CTL). Among all cell lines examined, Neuro 2a
      (a neuroblastoma) was readily infected with JEV as examined by immunofluorescence
      and viral replication. Among other cells, P388D1, RAW 264.7 (Macrophage origin),
      Sp2/0 (B-cell Hybridoma), YAC-1 (T-cell lymphoma), and L929 (Fibroblast) were
      semipermissive to JEV infection. The cytopathic effects caused by progressive JEV
      infection varied from cell line to cell line. In the case of YAC-1 cells long
      term viral antigen expression was observed without significant alterations in
      cell viability. Intermediate degrees of cytopathicity are seen in RAW 264.7 and
      L929 cells while infection of PS, Neuro 2a, P388D1 and Sp2/0 caused major
      viability losses. All infected cell lines were able to prime adult BALB/c (H-2d)
      mice for the generation of secondary JEV specific CTL. In contrast to YAC-1, the
      permissive neuroblastoma cell line Neuro 2a (H-2KkDd) was found to be least
      efficient in its ability to stimulate anti-viral CTL generation. Cold target
      competition studies demonstrated that both Neuro 2a and YAC-1 (H-2KkDd) cells
      expressed similar viral determinants that are recognised by CTL, suggesting that
      the reason for the lower ability of Neuro 2a to stimulate anti-viral CTL was not
      due to lack of viral CTL determinants. These findings demonstrate that a variety
      of mouse cell lines can be infected with Japanese encephalitis virus, and that
      these infected cells could be utilised to generate virus specific CTL in BALB/c
      mice.

PMID- 7646338
TI  - Ultrastructural and replicative features of foot-and-mouth disease virus in
      persistently infected BHK-21 cells.
AB  - Persistent foot-and-mouth disease (FMD) virus infection in vitro has been studied
      in a chronically infected cloned BHK-21 cell line. Virus growth during serial
      cell passages was followed by infectivity assay and immunocytochemical staining.
      Only a small percentage of cells (0.006-6%) was found to harbour virus during
      persistence. Light and electron microscopy showed the presence of cytoplasmic
      protuberances ("blebs") at the surface of persistently infected cells. The curing
      of cell cultures was achieved by passaging them in the presence of polyvalent
      immune serum. The absence of virus in cured cells was confirmed by infectivity
      assay and immunocytochemistry. This finding, together with the low percentage of
      infected cells in cultures confirms that persistently infected BHK-21 cells
      satisfy the definitions of a carrier culture. The characteristics of the in vitro
      system and its relevance to the study of FMD carrier state in vivo are discussed.

PMID- 7646339
TI  - A novel complex formed between the flavivirus E and NS1 proteins: analysis of its
      structure and function.
AB  - We examined the structural features and functional significance of a novel
      complex which forms between the envelope (E) protein and nonstructural protein
      NS1 of Murray Valley encephalitis (MVE) virus. Western blot analysis of virus
      infected C6/36 cell lysates revealed that the undenatured form of this E-NS1
      complex was a heat-sensitive E-(NS1 dimer) complex. Furthermore, the E-NS1
      complex was observed in cells infected with Kunjin, Japanese encephalitis, West
      Nile and Kokobera viruses which indicates the complex is a common feature of
      flavivirus infection. E-NS1 complex which had been immunoaffinity purified from
      MVE-infected cell lysates or eluted from gel slices exhibited partial breakdown
      into the individual monomers, demonstrating that the complex arose from the
      association of E and NS1 proteins and was not a single polypeptide created from
      incomplete gene cleavage. Radioimmunoprecipitation and western blot analysis of
      MVE-infected cell lysates and culture fluid preparations collected at various
      times after infection revealed that the E-NS1 complex has a long half life,
      accumulates in the virus-infected cell with time and is not secreted into the
      extracellular fluid. We have postulated that the E-NS1 complex, or at least a
      major portion of the complex, is a non-specific aggregation with no functional
      significance in the viral life cycle.

PMID- 7646340
TI  - Coat protein gene sequence of an Austrian isolate of grapevine fanleaf virus.
AB  - The nucleotide sequence of the coat protein cistron of an Austrian isolate of
      grapevine fanleaf virus (GFLV-FC) from Vitis vinifera cv. French Colombard was
      determined. It shows small differences at the RNA level as well as at the protein
      level compared to the sequences of already published grapevine fanleaf virus
      strains. The differences may be a result of the natural variation among virus
      populations or a consequence of selection in a special host plant. As the virus
      RNA sequence reported here was isolated directly from its natural woody host by
      an immunocapture-PCR technique, passage of the virus through a herbaceous host
      could be avoided and a possible bias introduced by a different host environment
      was excluded. The sequence similarity of known GFLV coat protein cistrons to the
      sequence described is as high as among the other strains.

PMID- 7646341
TI  - Protection against hantavirus infection by dam's immunity transferred vertically
      to neonates.
AB  - Antibodies to hantavirus, Seoul type B-1 strain, vertically transferred to rat
      neonates prevented lethal as well as persistent infection. When relatively high
      titer viruses were inoculated into neonates, the mother's antibodies protected
      all the neonates from lethal virus infection. However, the antibodies could not
      protect all of the neonates from persistent infection but only half of them
      underwent persistent infection. The other half was completely cured but also
      became persistently infected when rechallenged with the active viruses after
      reaching maturity.

PMID- 7646342
TI  - Electron microscopic localization of ATPase activity in tobacco cells infected by
      tobacco etch potyvirus and tobacco mosaic virus.
AB  - Thin sections of leaves of plants infected by tobacco etch potyvirus (TEV) or
      tobacco mosaic virus (TMV) were examined for the presence of ATPase activity by
      electron microscopy. ATPase activity was found as expected in mitochondria,
      chloroplasts and plasmalemma of both uninfected as well as cells infected by
      either TEV or TMV. In the TEV-infected cells, ATPase activity was localized to
      virus-induced vesicles, endoplasmic reticulum and in some cells, to ribosomes
      attached to the ER. In TMV-infected cells, ATPase activity was found in vesicles
      as well as in tubular membranes closely associated with the X-bodies.

PMID- 7646343
TI  - Influence of tyrosine residues Y705 and Y807 on the transforming potency of the v
      fms oncogene product of feline sarcoma virus.
AB  - Cell transformation is characterized by overt changes in growth control and cell
      morphology. To study the role of tyrosine residues Y705 and Y807 of v-Fms of the
      McDonough strain of feline sarcoma virus in cell transformation we replaced them
      individually with phenylalanine residues. Cells expressing the mutant genes
      showed mitogenic properties similar to wild-type v-Fms transformed cells.
      However, the morphology of cells expressing the Y807F mutant remained the same as
      nontransformed cells. Four phosphoproteins of 190, 120, 55 and 50 kDa were
      detected in cells expressing the wild-type but were absent in cells expressing
      the mutant Y807F-v-fms gene.

PMID- 7646345
TI  - Molecular cloning and physical mapping of porcine adenovirus types 1 and 2.
AB  - The 25R strain of porcine adenovirus type 1 (PAV-1) and the A47 strain of PAV-2
      were propagated in ST cells, and DNA was extracted from the infected cells by a
      modified Hirt method. The DNA of each virus was digested by each of nine
      restriction endonucleases, and restriction enzyme fragments representing the
      entire genome were cloned. The genomic size of each virus was approximately 33
      kb. Physical maps for the nine restriction endonucleases were constructed from
      the results of double digestion and Southern blot hybridization experiments, and
      oriented with respect to the PAV-3 genome. PAV-1 and PAV-2 were found to be
      related genetically to PAV-3, and there was a closer relationship between PAV-1
      and PAV-3 than between PAV-1 and PAV-2 or between PAV-2 and PAV-3.

PMID- 7646344
TI  - Transfection of Sendai virus F gene cDNA with mutations at its cleavage site and
      HN gene cDNA into COS cells induces cell fusion.
AB  - In contrast to the wild type Sendai virus fusion protein (F), a mutated F to
      possess a cleavage site similar to that of virulent Newcastle disease virus F,
      could be cleaved by proteases present in COS cells. When mutated F and
      hemagglutinin-neuraminidase (HN) were coexpressed at the cell surface, syncytium
      formation was observed.

PMID- 7646346
TI  - The immunogenicity of reassortants of the cold-adapted influenza A master strain
      A/Ann Arbor/6/60 is determined by both the genes for cold-adaptation and the
      haemagglutinin gene.
AB  - Two surface antigen segregants were prepared by co-infection of chicken embryo
      kidney cell cultures with reassortants of the cold-adapted influenza A master
      strain A/Ann Arbor/6/60-ca (H2N2) possessing the surface antigens of
      A/Queensland/6/72 (H3N2) and A/Hong Kong/123/77 (H1N1) and other genes that were
      common to the master strain. The segregants were shown by serological tests to
      possess H3N1 and H1N2 surface antigens but it was not possible to determine the
      presence of H1 or N1 genes by single-stranded RNA polyacrylamide gel
      electrophoresis. The immunogenic properties of A/Queensland/6/72-ca and H3N1
      segregant CR6/35/2/9 were compared by immunising mice intranasally with graded
      doses of each virus twice at an interval of 3 weeks and then challenging with the
      wild-type A/Queensland/6/72 (H3N2). Clearance of the challenge virus occurred in
      mice immunised with the same vaccinating dose, indicating that the immunogenicity
      of both the ca H3N2 and H3N1 viruses was identical and similar findings were
      obtained for mice immunised with A/Hong Kong/123/77-ca and the H1N2 segregant
      CR6/35/1/19 and challenged with the wild-type A/Hong Kong/123/77. Therefore,
      there appears to be a good correlation between immunogenicity and the inheritance
      of the haemagglutinin gene.

PMID- 7646348
TI  - Phylogenetic analysis of the long terminal repeat of feline immunodeficiency
      viruses from Japan, Argentina and Australia.
AB  - The nucleotide sequences of the long terminal repeat of five Japanese, five
      Argentine and three Australian isolates of feline immunodeficiency virus (FIV)
      were determined and compared with those of isolates previously described. The
      results revealed that the Japanese isolates were found to cluster with nucleotide
      sequence similarity of 95.6%-99.4%. The Australian isolates also clustered with
      nucleotide sequence similarity of 97.2%-99.4%. The Argentine isolates formed two
      groups; the LP9 isolate is closely related to the Japanese isolates, whereas the
      LP1, LP3, LP20 and LP24 isolates are distant from both the Japanese and
      Australian isolates. From these results, FIV can be divided into three groups,
      namely: (I) the Californian, Australian and British isolates; (II) the Japanese
      isolates and one Argentine LP9 isolate; (III) the other Argentine isolates.

PMID- 7646347
TI  - Nucleotide sequence analysis of an infectious laryngotracheitis virus gene
      corresponding to the US3 of HSV-1 and a unique gene encoding a 67 kDa protein.
AB  - The DNA sequence of 4005 nucleotides from the Kpnl O and part of Kpnl K fragments
      in the short unique region of infectious laryngotracheitis virus (ILTV) was
      determined. The sequence contained two complete and one partial open reading
      frames (ORFs). The partial ORF was open at the 5' end of the sequence and
      represented the NH2-terminal 118 amino acids (aa) of a polypeptide. Its partial
      predicted protein product exhibited significant homology to the US2 gene product
      of HSV-1 (herpes simplex virus type 1) and it homologs in other herpesviruses.
      ORF 2 is 471 aa long and could encode a protein of 53.8 kDa which shared aa
      homology with the protein kinases encoded by HSV-1 US3 and its gene homologs.
      Analysis of the ORF 2 aa sequence revealed domains characteristic of protein
      serine/threonine (S/T) kinases of cellular and viral origin. The ORF 3 encoded a
      predicted protein of 601 aa (M(r) 67.5 kDa) which exhibited limited homology (18%
      overall identity) with the UL47 protein (major tegument protein) of HSV-1.
      Northern (RNA) blot hybridization and metabolic inhibitors were used to
      characterize the ILTV protein kinase and the 67K mRNAs. The data revealed that
      protein kinase is a gamma-1 gene encoding a 1.6 mRNa, while the 67K ORF is a
      gamma-2 gene encoding a 2 kb mRNA.

PMID- 7646349
TI  - Characterization of protein involvement in rabies virus binding to BHK-21 cells.
AB  - Prior studies established the specificity of rabies virus receptors on BHK-21
      cells based on the saturability of the receptors and on competitive binding. In
      the present study, we used protease-treated cells to identify the involvement of
      protein in the specific binding of rabies virus to these cells. In addition,
      biochemical characterization of n-octylglucoside solubilized BHK-21 plasma
      membranes demonstrated the involvement of a protease sensitive, heat insensitive,
      integral membrane protein or protein complex in rabies virus binding to these
      cells. The membrane component that binds rabies virus is associated with a high
      molecular weight fraction of the n-octylglucoside-plasma membrane extract
      isolated by gel filtration. This high molecular weight fraction (approximately
      450 KDa) is enriched with a cell surface integral membrane component that
      comigrates with denatured bovine serum fibronectin (220 KDa). This cellular
      component did not bind polyclonal antisera to fibronectin in Western blot (native
      or denatured) or immunoprecipitation experiments. Direct and specific virus
      binding to high molecular weight plasma membrane protein(s) separated on Western
      blots further confirmed the role of a protein receptor in rabies virus binding to
      these cells.

PMID- 7646350
TI  - Perpetuation of influenza A viruses in Alaskan waterfowl reservoirs.
AB  - To provide information on the mechanism of perpetuation of influenza viruses
      among waterfowl reservoirs in nature, virological surveillance was carried out in
      Alaska during their breeding season in summer from 1991 to 1994. Influenza
      viruses were isolated mainly from fecal samples of dabbling ducks in their
      nesting places in central Alaska. The numbers of subtypes of 108 influenza virus
      isolates were 1 H2N3, 37 H3N8, 55 H4N6, 1 H7N3, 1 H8N2, 1 H10N2, 11 H10N7, and
      H10N9. Influenza viruses were also isolated from water samples of the lakes where
      they nest. Even in September of 1994 when the most ducks had left for migration
      to south, viruses were still isolated from the lake water. Phylogenetic analysis
      of the NP genes of the representative isolates showed that they belong to the
      North American lineage of avian influenza viruses, suggesting that the majority
      of the waterfowls breeding in central Alaska migrate to North America and not to
      Asia. The present results support the notion that influenza viruses have been
      maintained in waterfowl population by water-borne transmission and revealed the
      mechanism of year-by-year perpetuation of the viruses in the lakes where they
      breed.

PMID- 7646351
TI  - Ultrastructure and immuno-cytochemistry of BHK-21 cells infected with a modified
      Bucyrus strain of equine arteritis virus.
AB  - Morphogenesis of a modified Bucyrus strain of equine arteritis virus (EAV) in BHK
      21 cells was studied. Bacillary tubules were first detected in the cytoplasm 8 h
      after infection, and mature virions 79 to 122 nm in diameter, 101 nm on average,
      were mostly observed in the cisternae of the rough endoplasmic reticulum (RER) at
      12 h or later. They had isometrical cores and morphological subunits in the outer
      layer. Budding occurred from the RER and the outer nuclear membrane, but not from
      the cell surface. Structural linkage was detected between the tubule and the
      virus core. Aberrant strands were occasionally demonstrated within the nucleus 12
      h after infection, and immunofluorescence and immunogold labeling revealed viral
      antigen also in the nucleus.

PMID- 7646352
TI  - HSV type 1 genome variants from persistently productive infections in Raji and
      BJAB cell lines.
AB  - We studied possible genomic changes occurring in herpes simplex virus type 1 (HSV
      1) during long-term cell culture which served as a model system for persistence
      and latency studies as introduced earlier. Sixteen HSV-1 reisolates were isolated
      from persistently productive HSV-1 (strains F and AK)-infected Burkitt lymphoma
      cell lines Raji and BJAB at four different times. They were roughly characterized
      in plaque morphology, plaque size, and infectivity. The viral reisolate DNAs
      revealed deletions and insertions of up to 1,150 base pairs in fragments BamHI-B,
      -E, -F, -J, -V, -X, and in the L-terminal and junction fragments S and K. Results
      were confirmed by additional restriction enzyme analyses and DNA sequencing of
      selected genomic regions between map units 0.642-0.650, 0.763-0.778 and 0.887
      0.934. There was a progressive increase in genomic variability over a three-year
      period. However, changes in DNA fragment size occurred at different rates, with
      some reisolates showing stability over several months. The selective pressure for
      HSV-1 (F and AK) genomic changes was stronger in Raji than in BJAB cells, and
      stronger for F than for AK strain.

PMID- 7646353
TI  - Genomic relationship of porcine hemagglutinating encephalomyelitis virus to
      bovine coronavirus and human coronavirus OC43 as studied by the use of bovine
      coronavirus S gene-specific probes.
AB  - The genomic relationship of porcine hemagglutinating encephalomyelitis virus
      (HEV) to bovine coronavirus (BCV) and human coronavirus (HCV) strain OC43 was
      examined by dot blot hybridization assays. Two BCV S gene-specific probes were
      generated by polymerase chain reaction from the avirulent L9-strain of BCV.
      Probes were located in the S1 and the S2 region of the peplomeric (S)
      glycoprotein gene. The S1 probe (726 bp) hybridized with BCV and HCV-OC43, but
      not with HEV under moderate stringency hybridization conditions (50 degrees C).
      Only slight signals were present with mouse hepatitis virus (MHV) and no signals
      were observed with feline infectious peritonitis virus (FIPV) or canine
      coronavirus (CCV). At high stringency conditions (60 degrees C) the S1 probe
      hybridized with BCV only. Using the S2 probe (680 bp) under moderate stringency
      conditions, hybridization signals were obtained with BCV, HCV-OC43 and HEV
      (strains 67N, NT9, VW572). The signals obtained by the three HEV strains were
      altogether weaker than with BCV and HCV-OC43. The S2 probe did not react with
      MHV, FIPV and CCV. At high stringency the S2-specific probe hybridized with BCV
      and HCV-OC43 but did not hybridize with HEV. Nucleotide sequence analysis of the
      region covering the S2 probe in HEV revealed 92.6% nucleotide sequence homology
      to BCV and 91.9% to HCV-OC43. In contrast, the region covering the S1 probe in
      HEV could not be amplified using the BCV S1-specific primers. The hybridization
      and sequencing results thus indicate a closer genomic relationship between BCV
      and HCV-OC43 than there is between HEV and BCV or HCV-OC43 respectively.

PMID- 7646355
TI  - The complete nucleotide sequence of apple mosaic virus RNA-3.
AB  - The complete nucleotide sequence of apple mosaic ilarvirus (ApMV) RNA-3 has been
      determined from cloned viral cDNAs. The 5' terminus of RNA-3 was determined by
      direct RNA sequencing, while the 3' end was determined by polyadenylation of
      genomic RNA and sub-cloning using oligo dT. ApMV RNA-3 is 2056 bases in length
      and encodes at least two open reading frames. It is similar in size and genome
      organization to the RNA-3 of other members of the Bromoviridae, which includes
      ilarviruses. The CP gene is in the 3' half of the molecule, and another large
      open reading frame is upstream of the CP gene and can potentially encode a
      protein of 32,400 daltons. This peptide is the same size and shows limited
      sequence homology to an open reading frame located at the 5' end of RNA 3 in
      tobacco streak and prune dwarf ilarviruses and alfalfa mosaic virus, which is
      postulated to be the viral movement protein. The nucleic acid sequence was not
      homologous to tobacco streak virus, prune dwarf virus, alfalfa mosaic virus or
      other members of the Bromoviridae. The 5'-non-coding region of ApMV RNA-3
      contains a 15 base palindromic sequence which encloses a sequence resembling the
      ICR-2 regions of eukaryotic tRNA gene promoters.

PMID- 7646354
TI  - Specific T-cell response correlates with resistance of genetic heterogeneous
      mouse populations to mouse hepatitis virus 3 infection.
AB  - In a recently published study [Vassao RC, Mello IGC, Pereira CA (1994) Arch Virol
      137: 277-288] we have shown that the genetically selected high antibody responder
      mice (HIII) are susceptible and the low antibody responder counterparts (LIII)
      are resistant to death induced by experimental infection with mouse hepatitis
      virus 3 (MHV3). This report shows that the MHV3 titers in the peritoneal exudate
      (PE) of HIII mice, 3 days after infection, were more than 2 log greater than in
      the resistant LIII mice, the interferon gamma (IFN gamma) titers in the PE of
      both mouse populations being not significantly different. The treatment with
      monoclonal antibodies (mAb) against CD4+ or CD8+ T cells induced susceptibility
      among LIII mice. The depletion of CD4+ T-cell subset in LIII mice was evidenced
      by, and led to a significant reduction in, the IFN gamma synthesis in their PEs
      with a 100 fold increase in MHV3 titers. When lymph node cells (LNC) were
      harvested from MHV3-infected mice and stimulated "in vitro" with MHV3 inactivated
      by ultraviolet radiation (uv-MHV3), only LNC from LIII mice were capable of
      proliferating and synthesizing significant amounts of interleukin 2 (IL-2). The
      LNC proliferation and IL-2 synthesis were inhibited by treatment with mAbs
      against CD4 or CD8 molecules. The MHV3 infection induced in both lines of mice a
      profound depression of the mitogenic response of LNC to phytohemaglutinin (PHA).
      A correlation between the specific T-cell response and the resistance to MHV3
      infection is discussed.

PMID- 7646356
TI  - Epitope mapping of dengue 1 virus E glycoprotein using monoclonal antibodies.
AB  - Ten monoclonal antibodies (MAbs) were raised against dengue 1 (DEN 1, Hawaii)
      virus E glycoprotein. Specificity of the MAbs was tested by ELISA and
      immunofluorescence. Eight were DEN 1 type-specific, one was DEN group-reactive
      (DGR) and one was flavivirus cross-reactive (FCR). Two of these type specific
      MAbs exhibited haemagglutination-inhibition (HI) and neutralized (N) DEN 1 virus
      in vivo (HS). These two MAbs showed 100% protection against a challenge of 100
      LD50 of DEN 1 virus in adult Swiss albino mice. The remaining six MAbs were HI
      negative, N negative and non-protective against challenge (NHS). Of these only
      three were reactive in the CF test. The DGR, FCR and one of the NHS MAbs (NHS-3)
      did not react with DEN 1 virus grown in Vero cells, whereas they reacted with DEN
      1 virus grown in LLC-MK2 and C6/36 cells in immunofluorescence, probably
      indicating a difference in the synthesis/processing of viral proteins in these
      different cell lines. An epitope map of the E gp was drawn using a computer
      programme based on the additivity index values. The epitope map delineated five
      domains, a) S-I representing type-specific, HI positive, N positive and
      protecting MAbs. b) S-II representing type-specific, HI negative, N negative
      MAbs. c) S-III representing type-specific HI/N negative MAb, but distinct from S
      II. d) DGR representing HI/N negative DEN group reactive MAb. e) FCR representing
      HI/N negative flavivirus cross-reactive MAb. Epitope analysis of a number of
      different DEN 1 strains isolated in India over a period of 30 years showed that
      the domains S-II and S-III which react with HI negative, DEN-1 specific MAbs were
      variable. The DGR domain and the S-I domains were conserved.

PMID- 7646357
TI  - Detection of a picobirnavirus associated with Cryptosporidium positive stools
      from humans.
AB  - A picobirnavirus with an atypical genome profile was detected by polyacrylamide
      gel electrophoresis (PAGE) in 37% (20/54) of human faecal samples also containing
      oocysts of Cryptosporidium typical of C. parvum. This virus shares many of the
      characteristics of the previously described picobirnaviruses, but has a
      significantly smaller genome (1.75 and 1.55 Kbp).

PMID- 7646358
TI  - Comparative nucleotide and deduced amino acid sequence analysis of VP7 gene of
      the NCDV Cody (I-801) strain of group A bovine rotavirus.
AB  - The prevalent G serotypes of group A bovine rotavirus (BRV) reported are G6, G10,
      and less commonly, G8. Neonatal Calf Diarrhea Virus (NCDV), Lincoln and Cody
      strains were first isolated from diarrheic calves in Nebraska. The NCDV Lincoln
      strain is the currently used U.S. vaccine strain and has a G6 serotype. In this
      study, the complete nucleotide sequence of the VP7 gene of NCDV Cody (I-801
      strain) was determined using the primer extension method. The VP7 gene nucleotide
      sequence homologies between Cody I-801 and established G8 rotaviruses, A5
      (Thailand BRV), 678 (UK BRV), B37 (human RV) and 69M (human RV) were 84.7%,
      86.4%, 84.7% and 85.9%, respectively. The deduced VP7 amino acid sequence of Cody
      I-801 was similar to that of A5, 678, B37 and 69M (93.6%, 95.7%, 92.6% and 95.1%,
      respectively). The VP7 gene nucleic acid sequence homologies between NCDV Cody (I
      801) and NCDV Lincoln or B223 (G10) was 76.2% and the deduced VP7 amino acid
      sequence homologies between Cody I-801 and NCDV Lincoln or B223 were 82.5% and
      81.3%, respectively. Thus, our sequence data suggests that the VP7 gene of Cody I
      801 strain of BRV is genetically most similar to G8 rotaviruses and unrelated to
      the NCDV Lincoln G6 rotavirus strain.

PMID- 7646359
TI  - The 5'-untranslated region sequence of a potential new genotype of bovine viral
      diarrhea virus.
AB  - The 5' untranslated region (UTR) of several bovine viral diarrhea virus (BVDV)
      isolates from the severe Quebec outbreak was amplified by polymerase chain
      reaction (PCR) and sequenced. Sequences revealed the loss, for the BVDV type II
      isolates, of an internal PstI restriction site, which is present in all known
      BVDV type 1 5' UTR sequences. A single restriction enzyme digestion (PstI) of an
      aliquot of PCR product allowed us to differentiate BVDV type I and BVDV type II.

PMID- 7646360
TI  - Immunoelectron microscopic study of HTLV-II-producing cells with an anti-envelope
      gp46 monoclonal antibody.
AB  - We observed expression of envelope gp46 protein on an HTLV-II-producing T-cell
      line (Mo) cells by an immunoelectron microscopical method using a monoclonal
      antibody against HTLV-II gp46. gp46 reactivity was observed on virus-like
      particles, extracellular vesicles, cell membrane, and partially in nuclear
      membrane and endoplasmic reticulum.

PMID- 7646362
TI  - Antigenic and biological comparisons of bovine coronaviruses derived from
      neonatal calf diarrhea and winter dysentery of adult cattle.
AB  - The antigenic and biological properties of 6 strains of bovine coronavirus (BCV)
      derived from neonatal calf diarrhea (CD) and 8 strains of BCV from winter
      dysentery (WD) of adult cattle, propagated in HRT-18 cells, were compared to
      determine if CD and WD strains belong to distinct serotypes or subtypes of BCV.
      All strains hemagglutinated both mouse and chicken erythrocytes at 4 degrees C,
      but the ratios of hemagglutination titers with mouse erythrocytes compared to
      chicken erythrocytes showed diversity for both CD and WD strains. Some CD and WD
      strains did not hemagglutinate chicken erythrocytes at 37 degrees C and showed
      receptor-destroying enzyme activity against chicken erythrocytes. Hyperimmune
      antisera were produced in guinea pigs against 3 and 7 strains of BCV from CD and
      WD, respectively. No significant differences in antibody titers against these
      strains were observed by indirect immunofluorescence tests. However, in virus
      neutralization tests, antisera to 1 CD and 2 WD strains had 16-fold or lower
      antibody titers against 3 WD and 1 CD strains than against the homologous
      strains, and this variation reflected low antigenic relatedness values (R = 13
      25%), suggesting the presence of different subtypes among BCV. In
      hemagglutination inhibition tests, some one-way antigenic variations among
      strains were also observed. These results suggest that some antigenic and
      biological diversity exists among BCV strains, but these variations were
      unrelated to the clinical source of the strains; i.e. CD or WD.

PMID- 7646361
TI  - Antigenic homogeneity among the adenovirus hexon types of subgenus C.
AB  - Antigenic relationships of hexons of human adenovirus (Ad h) types 1, 2, 5 and 6
      of subgenus C were studied with 61 monoclonal antibodies (MAbs) raised against
      human Ad h1, Ad h35 and bovine adenovirus 2. The reactivity pattern (RP) and the
      titers of the MAbs were determined in indirect ELISA. In previous experiments
      with hexons of different subgenera 49 MAbs displayed numerous different intertype
      specificities besides genus specific and type specific ones. With the four hexon
      types of subgenus C all MAbs gave identical RPs except the type specific ones.
      Data reveal the existence of a remarkable homogeneity in the antigenic structure
      among the hexon types of subgenus C defined by the presence of identical or
      closely related intertype specific epitopes on the surface of the hexons. The
      possible significance of the results in the experimental gene therapy is
      discussed.

PMID- 7646363
TI  - Sequence analysis of open reading frames (ORFs) 2 to 4 of a U.S. isolate of
      porcine reproductive and respiratory syndrome virus.
AB  - The sequence of ORFs 2 to 4 of a U.S. isolate of porcine reproductive and
      respiratory syndrome virus (PRRSV), ATCC VR2385, was determined by analysis of a
      cDNA lambda library. The cDNA clones containing PRRSV specific sequences were
      selected using a VR2385 ORF 4 specific PCR probe and sequenced. The ORFs 2, 3 and
      4 overlapped each other and encoded polypeptides with predicted M(r) of 29.5 kDa
      (ORF 2), 28.7 kDa (ORF 3) and 19.5 kDa (ORF 4), respectively. No overlap was
      found between ORFs 4 and 5, and instead there was a 10 bp sequence which
      separated these two ORFs. The nucleic acid homology with corresponding ORFs of
      the European PRRSV isolate Lelystad virus (LV) was 65% for ORF 2, 64% for ORF 3
      and 66% for ORF 4. Comparison of the ORF 4 sequences of VR2385 with that of
      another U.S. isolate MN-1b revealed only 86% amino acid sequence homology and the
      presence of deletions in the ORF 4 of MN-1b. Our results further strengthen the
      observation that there is sequence variation between US and European PRRSV
      isolates.

PMID- 7646364
TI  - The Newcastle disease virus V protein binds zinc.
AB  - The V protein of Newcastle disease virus (NDV) is produced by the insertion of a
      single nontemplated G residue at a specific point during transcription of the
      phosphoprotein (P) gene, accessing a new reading frame upon translation. The V
      protein, in common with its counterpart in other paramyxoviruses contains a
      highly cysteine rich motif near the carboxyl terminus, suggestive of a zinc
      binding domain. By constructing E. coli overexpression plasmids for the NDV P and
      V proteins, and monitoring the binding of 65ZnCl2 to proteins electroblotted onto
      nitrocellulose membranes, we have demonstrated that the V protein strongly binds
      zinc.

PMID- 7646365
TI  - The National Institute for Medical Research, Mill Hill.

PMID- 7646366
TI  - A listing of virus families and genera with some discriminatory features.

PMID- 7646367
TI  - [Free radical and allergy].

PMID- 7646368
TI  - [Investigation of mites in the houses of atopic dermatitis (AD) patients, and
      clinical improvements by mite elimination].
AB  - Seasonal variations related to mites were investigated by the Methylene Blue Agar
      (MBA) method in the houses of 157 AD patients living in Tokyo. Many mites were
      counted in the dust from carpets, Japanese straw mats (Tatami) and the floor
      under Tatami. In most places, the number of mites was found to increase in
      summer. In winter, however, mite levels increased in sofas and Japanese seat
      cushions. On the other hand, only small numbers of mites were found in mite-proof
      products. Based on the above data, were recommended mite elimination by various
      scientific techniques was recommended for 34 severe AD patients. Mite levels and
      clinical symptoms were again checked after one year and two years in the same
      seasons. In 17 of the 34 cases, mite elimination was carried out completely. In
      these cases, the ratio of mite decrease to less than 30% was 82%, and the ratio
      of improvement of clinical symptoms (remarkable improvement + improvement) was
      88%. Almost complete cure was noted in 7 cases. On the other hand, in the
      remaining 17 cases, mite elimination was performed incompletely in 12 cases, and
      was hardly done at all in 5 cases. The ratio of mite decrease to less than 30%
      was 47%, and the ratio of improvement of clinical symptoms was 35%. Therefore, it
      was concluded that investigation of mite levels following mite elimination
      procedures is a most recommendable treatment for severe AD patients who are
      hypersensitive to house dust mites.

PMID- 7646369
TI  - [The correlation between the levels of anti-Malassezia furfur IgE antibodies and
      severities of face and neck dermatitis of patients with atopic dermatitis].
AB  - It is well known that the seborrheic areas including the face and neck of
      patients with atopic dermatitis (AD) are frequently affected after adolescence.
      Malassezia furfur (MF), a lipophilic yeast and a normal habitat of seborrheic
      areas, has been thought to be one of the most important factors in provoking face
      and neck lesions of AD. In the present study, we assessed serum levels of anti-MF
      IgE antibodies by enzyme-linked immunosorbent assay (AlaSTAT method) in 123
      adolescent and adult AD patients and evaluated the correlations between levels of
      anti-MF IgE and those of total IgE and some other allergen-specific IgE. The
      correlation between the levels of anti-MF IgE and severities of face and neck
      dermatitis was also assessed. Anti-MF IgE antibodies were detected in high
      frequency in AD patients (77%), while they were not found in controls.
      Significant correlations were noted between the levels of anti-MF IgE and those
      of total IgE and anti-Candida IgE. The levels of anti-MF IgE were well correlated
      with the severities of face and neck dermatitis. These result may indicate that
      MF is an important provocative factor for face and neck dermatitis in AD
      patients.

PMID- 7646371
TI  - [Psychological profiles of patients with bronchial asthma (II). Analysis
      according to the modes of attack in severe asthmatics and in those with fatal
      asthma].
AB  - When the rise of asthma death became a world-wide problem, background factors
      proposed were the poor patient education and compliance with psychological
      factors which hindered these accomplishments. Analysis were made on the
      psychological test scales recorded by the severe asthmatics and found that the
      result for the acute type resembled the controls, while those with chronic
      attacks had depressive/neurotic tendencies with decreased activity. Result of
      those with acute on chronic attacks show more active attitude in life. Fatal
      asthmatics had high level for thinking extroversion signifying more optimistic
      attitude which may have lead them to their under-estimation of asthma. Other
      scales in fatal asthma suggest problems in their life styles and maladaptation.

PMID- 7646370
TI  - [Detection of IgE antibodies to salt-insoluble wheat proteins in sera of patients
      with atopic dermatitis by ELISA and immunoblotting techniques].
AB  - Specific IgE antibodies against salt-insoluble wheat proteins were investigated
      in sera from 60 patients with atopic dermatitis (AD) positive to wheat specific
      CAP-RAST. The salt-insoluble wheat protein fraction was prepared from whole
      protein fraction of wheat flour, which was extracted by PBS containing 6 M urea.
      IgE antibodies to salt-insoluble proteins were detected in 15 of the sera. IgE
      ELISA was applied to these 15 sera, with whole wheat proteins, salt-soluble
      proteins, and salt-insoluble proteins used as antigens. Wheat specific CAP-RAST
      values correlated well with the IgE-ELISA titers against salt-soluble proteins (r
      = 0.918 p < 0.001). On the other hand, IgE-ELISA titers against both the salt
      insoluble proteins and the whole wheat proteins correlated least with CAP-RAST
      values (r = 0.161 and r = 0.113). The inhibition tests indicated that IgE
      antibodies against salt-insoluble proteins were different from those against salt
      soluble ones. Thus, IgE antibodies to salt-insoluble proteins were another
      antigen target of IgE-mediated allergy manifestation. To determine the molecular
      weight of antigens reacting with IgE, IgE-immunoblotting was performed. Several
      polypeptides with molecular weights of 33-45, 84, 90 and 98 KD were detected.
      However, the antigen patterns of the blots varied depending on the sera used.
      These findings suggest that salt-insoluble wheat proteins are the major antigens
      in some wheat-dependent AD, and that IgE detection against salt-insoluble wheat
      proteins is important for the diagnosis of wheat allergy.

PMID- 7646372
TI  - [Air pollution (NO2, suspended particulate material) and the number of acute
      hospitalization of patients with asthmatic attack].
AB  - There were many reports about the relationship between the air pollution and the
      incidence of asthma. In Japan some of the concentrations of air pollutants, for
      example, SO2, CO, have been reduced in these ten-twenty years. However the
      concentrations of suspended particulate material (SPM) and NO2 have not been
      reduced, and the incidence of bronchial asthma have been increasing gradually.
      The relationship between the concentrations of NO2, SPM and the number of
      patients admitted to our hospital because of asthmatic attack was studied. The
      concentration of each air pollutant was measured at the air quality monitoring
      stations in Minami-ku and Jonan-ku Fukuoka, Japan. Between Jan, 1988 and Dec.
      1991, 3661 patients with asthmatic attacks were admitted to our hospital. The
      relationship between the monthly averaged one-hour mean value for a day, and
      monthly max. of one-hour mean. value for a day, and one-day max. value for a
      month of NO2 and SPM and the numbers of asthmatic attack patients admitted was
      evaluated. There was a statistically significant relationship between
      concentrations of NO2 and SPM levels and the numbers of asthmatic patients
      admitted aged 6 or less. However, there was no such a relationship when the
      patients were aged between 7 and 20. These results suggested that the airways of
      asthmatic patients in the age of 6 or less might be more sensitive to NO2 and SPM
      than that of those patients in the age of 7 to 20.

PMID- 7646373
TI  - High-molecular-size mite allergens with high carbohydrate content in mite extract
      containing mite feces of Dermatophagoides farinae.
AB  - A series of mite allergens with high carbohydrate content was fractionated from
      mite extract containing mite feces by ultrafiltration, and successive
      chromatography on Ultrogel AcA 54, Sepharose CL-6B, and DEAE Toyopearl 650S. The
      final fractions isolated were termed HM1-2-Eff, -0.1A, -0.1B, -0.3A, -0.3B, and 
      1M according to the eluted salt concentration. These six fractions were stained
      weakly with Coomassie Brilliant Blue but strongly with periodate-Schiff's reagent
      on SDS-PAGE. Their molecular weight were estimated to be 150-155 KD on Sepharose
      CL-6B. All of these six fractions provoked strong erythema in skin of mite
      sensitive and asthmatic patients. HM1-2-Eff, -0.1A, -0.1B and -0.3B reacted with
      73% of mite-sensitive patients' IgE by the nitrocellulose dot blotting. One ng/ml
      of 4 fractions (HM1-2-0.1A, 0.3A, 0.3B and -1M) released histamine from mite
      allergic patient's blood cells. HM1-2-0.3A induced proliferation of T cell from
      immunized mouse by mite extract containing mite feces (Dff).

PMID- 7646374
TI  - Contribution of platelet activating factor (PAF) in histamine-induced model of
      nasal allergy in rats.
AB  - Histamine-induced nasal hyperpermeability was measured in rats. Perfusion of
      histamine elicited a biphasic increase of nasal vascular permeability, and an
      increase of concentration of platelet-activating factor (PAF) in the perfusate.
      Both phases were prevented by pretreatment with diphenhydramine (1 mg/kg, p.o.),
      a histamine H1-receptor antagonist, and the second increase of vascular
      permeability was prevented by pretreatment with 3-[4-(2-chlorophenyl)-9-methyl-6H
      thieno [3,2-f] [1,2,4]-triazolo [4,3-alpha] [1,4] diazepin-2-yl]-1-(4
      morpholinyl)-1-propane (WEB 2086) (10 mg/kg, p.o.), an anti PAF agent. The time
      course of PAF-induced nasal hyperpermeability was similar to that of the second
      increase induced by histamine. These findings suggest that PAF released by
      histamine from nasal mucosa plays an important role in nasal allergy, especially
      in the late phase.

PMID- 7646375
TI  - Post-prandial serum bile acid concentrations and ammonia tolerance in Maltese
      dogs with and without hepatic vascular anomalies.
AB  - Post-prandial serum bile acid concentrations were measured in 200 Maltese dogs in
      an attempt to identify those with subclinical portosystemic shunts. Five of these
      were later shown to have hepatic pathology or abnormal liver function. In the
      other 195 Maltese, bile acid concentrations ranged from 1 to 362 mumol.L-1 (mean
      +/- SD, 70 +/- 50 mumol.L-1; median, 65.0 mumol.L-1). Of these, 79% were above
      the reference range (0 to 31 mumol.L-1) established from 23 mixed-breed control
      dogs. It was therefore not possible to determine the prevalence of subclinical
      portosystemic shunts on the basis of bile acid determinations. Further
      investigation of liver function was performed to investigate why bile acid
      concentrations were increased in these dogs. Rectal ammonia tolerance tests were
      normal in 102 of 106 Maltese tested and liver samples (11 dogs) and plasma
      biochemistry profiles (9 dogs) demonstrated no significant hepatic disease or
      dysfunction. Of 2 Maltese with hyperammonaemia after administration of ammonium
      chloride, one had a large congenital portosystemic shunt that was confirmed at
      surgery. In the other there were no macroscopic portosystemic communications, but
      a liver biopsy showed histological changes consistent with microscopic
      portovascular dysplasia. Total serum bile acid concentrations were consistently
      lower when assessed by high-performance liquid chromatography than by an
      enzymatic spectrophotometric method. This discrepancy was substantially larger in
      Maltese than in control dogs, suggesting the presence of an additional reacting
      substance in the serum of Maltese dogs.

PMID- 7646376
TI  - Pastoral development and the veterinary profession in Australia, 1850-1900.

PMID- 7646377
TI  - Observations on the indirect transmission of virulent ovine footrot in sheep
      yards and its spread in sheep on unimproved pasture.
AB  - Virulent ovine footrot was transmitted accidentally to a group of 23 adult Merino
      sheep (flock B) after holding for 1 hour in sheep yards, which earlier the same
      day had contained another flock (flock A) with < 1% prevalence of sheep with
      footrot lesions. Sheep in flock B were rendered susceptible to virulent footrot
      by grazing 600 mm high unimproved pasture dominated by paspalum (Paspalum
      dilatatum) and kangaroo grass (Themeda australis) during warm, humid and wet
      weather. In addition to moisture, interdigital abrasions caused by the pasture
      might have predisposed the interdigital skin to infection with Dichelobacter
      nodosus.

PMID- 7646378
TI  - The use of toltrazuril for the prevention of coccidiosis in piglets before
      weaning.
AB  - To determine the efficacy of toltrazuril as a prophylactic treatment for
      coccidiosis in piglets caused by Isospora suis (I suis), a single 1.0 mL dose of
      toltrazuril was administered orally to 1056 piglets between 3 and 6 days of age,
      in 5 piggeries. Prophylactic treatment of piglets reduced the occurrence of
      coccidiosis in litters from 71% to 22%. The number of antibacterial treatments
      given and the number of piglets affected per litter were also significantly
      reduced, resulting in some improvement in growth rates to weaning. The severity
      of diarrhoea was significantly reduced, as was the amount of oocyst excretion.
      The number of days that piglets excreted oocysts in the faeces was reduced from
      4.9 days to 2.5 days. The detection of I suis in piglets with diarrhoea was
      reduced from 84% in the untreated piglets to 6% in the piglets given the
      prophylactic treatment.

PMID- 7646379
TI  - The minor role of pigs in outbreaks of foot-and-mouth disease of northern
      Thailand.
AB  - A study was undertaken in northern Thailand to examine the involvement of pigs in
      outbreaks of foot-and-mouth disease (FMD). Data were collected by surveying
      selected villages, by serological monitoring of pigs and by investigating
      outbreaks. Fifty-three of 58 villages (91%) surveyed reported that pigs did not
      develop FMD during the most recent outbreak. The source of 49/60 (82%) outbreaks
      was attributed to either recent purchases of infected cattle and buffalo or
      commingling of cattle and buffalo with stock from an infected neighbouring
      village. One of 60 villages (1.7%) reported that the source was introduced
      infected pigs. There was no association between the various hypothesised risk
      factors relating to the management of pigs and the frequency of FMD outbreaks in
      the survey. The percentage of seropositive pigs during 3 rounds of serological
      monitoring conducted at 6-monthly intervals in selected villages was 3.5%, 2.6%
      and 0%, respectively. No clinically affected pigs were observed in 11 outbreak
      investigations. It was concluded that pigs did not commonly become infected when
      there were outbreaks of FMD in village cattle and buffalo in northern Thailand.
      This was probably due to the pig feeding and housing practices employed by
      villagers that protected pigs from exposure to virus from infected cattle or
      buffalo, or their products.

PMID- 7646380
TI  - Developing group practices: a management challenge.
AB  - The advantages and disadvantages of forming larger professional practices are
      often debated. This paper reports an exploration of the issues through three case
      studies involving clusters of Sydney general medical practitioners who had
      expressed a desire to amalgamate their solo or small group practices. Their most
      frequently stated goals were to reduce financial overheads, to improve the range
      of services offered to their patients and to improve the opportunities for
      recreational and study leave. Several barriers to successful amalgamation were
      identified, and methods of overcoming these were explored. Practices can
      successfully amalgamate, but only where there is a group of like-minded general
      practitioners who are willing to invest time to achieve mutually agreed
      objectives. Amalgamation will not be appropriate in all circumstances. Larger
      group practices should benefit from the employment of a professional practice
      manager. These findings may be relevant to veterinary and dental practices.

PMID- 7646381
TI  - Sudden blindness associated with protothecosis in a dog.

PMID- 7646382
TI  - Johne's disease in alpacas (Lama pacos) in Australia.
AB  - Johne's disease was diagnosed in 10 alpacas (Lama pacos) in Australia between
      February 1993 and May 1994. Eight of the animals were between 12 and 24 months of
      age, one was a 6-year-old female, and one was a 4-year-old male. Five, including
      the 6-year-old and the 4-year-old alpacas, showed weight loss and diarrhoea
      before death or slaughter. The other cases showed no clinical signs of Johne's
      disease but 4 gave a positive result on faecal culture and one gave a positive
      result on testing with the caprine AGID assay and had acid-fast organisms in its
      faeces. At necropsy, all cases had grossly enlarged mesenteric lymph nodes.
      Johne's disease was diagnosed after histological examination of the lymph nodes
      with conventional culture and polymerase chain reaction testing of tissue
      samples. This report outlines the clinical, epidemiological, and pathological
      findings in these cases.

PMID- 7646383
TI  - Ostrich anaesthesia: xylazine premedication followed by alphaxalone/alphadolone
      and isoflurane.

PMID- 7646384
TI  - The presence of Giardia and other zoonotic parasites of urban dogs in Hobart,
      Tasmania.

PMID- 7646385
TI  - Antimicrobial susceptibility of Pasteurella multocida isolates from cases of
      pneumonia in slaughter swine from south-east Queensland.

PMID- 7646386
TI  - Carmalt splinter forceps: a useful instrument.
AB  - Most dermatologic surgeons have favourite instruments that they like to use. One
      of mine is the Carmalt splinter forceps. These forceps are short (about 10 cm in
      length) and have triangular pointed tips with serrations that are kept in
      alignment by a small pin at the broadest area of the tip.

PMID- 7646387
TI  - Phototherapy burns and fluoxetine.

PMID- 7646388
TI  - Skin screening in health promotion.

PMID- 7646389
TI  - Female androgenetic alopecia: an update.
AB  - Androgenetic alopecia is an androgen dependent disorder occurring in genetically
      susceptible individuals. The pattern of hair loss in women differs from that of
      classical male pattern alopecia, being more diffuse and with retention of the
      frontal hair line in most cases. Characteristic histopathological changes occur
      but biopsy is rarely helpful in diagnosis. Although research has shown subtle
      alterations in the androgen status of women with androgenetic alopecia, most
      patients presenting with this disorder are normal endocrinologically. Anti
      androgen therapy will result in some improvement in up to 50% of patients after 6
      to 12 months of therapy, but in practice will usually only decrease the rate of
      hair loss and not result in new hair growth.

PMID- 7646390
TI  - Post-contact chronic eczema: pension or rehabilitation.
AB  - A proportion of patients who suffer from either irritant or allergic contact
      dermatitis, many of whom have no past or family history of atopy or of any other
      skin disease, evolve into chronic eczema. Workers' compensation payments are
      frequently suspended after about 6 to 12 months on the basis of 'endogenous
      dermatitis'. Patients, often healthy breadwinners in the 30 to 50 age group are
      deemed unemployable because of persistent active dermatitis. Expensive prolonged
      litigation frequently follows but the end result is usually a patient who has
      become a healthy, bored, pensioner/retiree with all the psychological and
      physical sequelae secondary to inactivity and major lifestyle change. It is now
      becoming recognized that there are many jobs which a person suffering from
      various degrees of chronic dermatitis can perform without aggravation of
      dermatitis. However, widespread acceptance of this tenet requires a change in
      attitude by all the players in the workers' compensation complex, namely the
      employer, the insurance company, the medical practitioner, the employee and the
      union. Fortunately, the emphasis is gradually changing towards multidisciplinary
      assessment of work potential with appropriate retraining and redeployment of
      injured workers rather than granting lump sum compensation payouts or pensions.

PMID- 7646391
TI  - The use of mimetic musculature in facial reconstruction.
AB  - Skin malignancy of all types is prevalent in Australia and the incidence is
      rising. Reconstruction of post-surgical excision defects in the face can be
      facilitated by the use of myocutaneous flaps using facial mimetic musculature.
      The mimetic musculature can be partially sacrificed without the loss of
      discernible facial tone or expression. Examples of their use include the
      frontalis, orbicularis oculi, nasalis, procerus, levator labii superioris,
      mentalis, orbicularis oris, platysma and SMAS. Myocutaneous flaps in the face
      enjoy the same advantages of increased skin viability as they do elsewhere in the
      body. Their use in the face is superior to the cosmetic results obtained by skin
      grafting alone or distant skin flap giving better colour match, increased
      vascularity and appropriate bulk when subcutaneous tissues and muscles have also
      been sacrificed in the initial extirpation of the skin malignancy.

PMID- 7646392
TI  - Employer attitudes toward persons with visible tattoos.
AB  - A total of 242 employers were surveyed over the telephone to assess their
      attitudes toward prospective employees with visible tattooing. Employers were
      divided into eight categories according to type of industry. Responses to the
      survey were tabulated and confidence intervals produced. It would appear that
      significant bias exists against the employment of persons with visible tattoos in
      the hospitality, beauty, retail and office sectors where less than 30% of those
      surveyed would employ a person with a tattoo. All industries except building and
      the public service admitted that they would be influenced by a visible tattoo in
      over 40% of cases.

PMID- 7646393
TI  - Cutaneous malignancies in renal transplant recipients from Nova Scotia, Canada.
AB  - Four hundred and seventy-four Nova Scotian renal transplant recipients were
      screened, using the records of the Nova Scotia Cancer Registry and the Victoria
      General Hospital, in a retrospective study, for the development of cutaneous
      malignancies. Sixteen patients developed a total of 60 squamous cell carcinomas
      (SCC) and 14 developed 28 basal cell carcinomas (BCC). The survival curve shows
      that within 10 years of transplant, less than 10% will develop SCC. This is a 16
      fold increase above the rate of SCC in the general population of Nova Scotia,
      Canada. Age at time of transplantation appears to be a significant determinant of
      subsequent skin cancer risk. None of the previously reported HLA associations was
      found to hold in this small study. The role of ultraviolet radiation, due to both
      geographic and lifestyle exposure, is discussed when comparing to other
      transplant studies.

PMID- 7646394
TI  - A case of Grzybowski's generalized eruptive keratoacanthomas.
AB  - We report a case of Grzybowski's generalized eruptive keratoacanthoma which
      demonstrates the characteristic features of this rare condition. The recurring
      nature of the eruption each summer supports the suggestion that UV irradiation
      may act as a precipitating factor in eruptive keratoacanthoma.

PMID- 7646395
TI  - The brown forehead ring: a pattern of facial pigmentation.
AB  - The brown forehead ring (linea fusca), a distinctive but infrequently recognized
      pattern of facial pigmentation, is described. The history of this sign is
      recounted. In modern times it seems to be associated with other well recognized
      patterns of facial pigmentation, chemical photosensitizers and excessive sun
      exposure. Three cases in adult males are described and the different aetiologies
      illustrated.

PMID- 7646396
TI  - Bazex syndrome (acrokeratosis paraneoplastica).
AB  - A 67 year old woman with an extensive oropharyngeal carcinoma developed
      acrokeratosis paraneoplastica. She suffered severe pain in the fingers and toes
      and experienced some symptomatic relief with psoralen ultraviolet A therapy.

PMID- 7646397
TI  - Keratotic basal cell carcinoma of the upper eyelid.
AB  - A 62 year old woman presented with two large slowly growing pedunculated tumours.
      These were excised from the lateral aspect of the upper eyelid and were found to
      be keratotic basal cell carcinomas.

PMID- 7646398
TI  - Bullous pemphigoid in an infant.
AB  - An acral blistering eruption in a 10 week old baby was found on histology and
      direct immunofluorescence to be bullous pemphigoid. Circulating auto-antibodies
      were not detected. He responded quickly to oral prednisolone and there have been
      no sequelae.

PMID- 7646399
TI  - Photoallergic dermatitis to a pig feed additive.

PMID- 7646400
TI  - Putting "human error" into perspective.

PMID- 7646401
TI  - Explanatory factors for the geographic distribution of U.S. civil aviation
      mortality.
AB  - BACKGROUND: State-specific aviation-related mortality rates differ substantially
      between various geographical regions of the United States. PURPOSE: The purpose
      of this study was to ascertain important explanatory factors that account for the
      geographical distribution of mortality. METHODS: National Center for Health
      Statistics sources were used to calculate state-specific, age-adjusted mortality
      rates. Fatalities studied were those attributed to select civil aviation-related
      causes (ICD-9 E-codes 840.2-.6, 841.2-.6, 842.2-.6) that occurred from 1979-89.
      State-specific information on a variety of selected variables was obtained from
      census, commerce, and Federal Aviation Administration (FAA) sources. Multiple
      linear regression techniques were used to assess the relationship between
      selected variables and state-specific mortality rates. RESULTS: There were 13,048
      deaths for a U.S. 11-year mean mortality rate of 4.9 deaths/1,000,000 general
      population. Mountainous states of the western U.S. had the highest 11-year mean
      mortality rates (range 8.6-79.6 deaths/1,000,000). Mid-Atlantic states had the
      lowest rates (range 1.6-2.9 deaths/1,000,000). Regression analysis identified
      pilot density (number of pilots per 1,000,000 general population), top elevation
      (highest point of land within state boundaries), and flight intensity (number of
      general aviation flight hours flown per pilot) as important factors in explaining
      92% of state mortality differences. CONCLUSIONS: Highest aviation-related
      mortality rates are found in states with expanses of mountainous terrain, and
      relatively high pilot densities and flight activity levels.

PMID- 7646402
TI  - Physiological assessment of the RNZAF constant wear immersion suit: laboratory
      and field trials.
AB  - Laboratory and field immersion trials were undertaken to determine the thermal
      protection afforded by a constant wear immersion suit (CWIS) in operation with
      the Royal New Zealand Air Force (RNZAF). Six males wore each of two ensembles
      during head-out laboratory immersions in 5.0 +/- 0.1 degree C (mean +/- SD) water
      for a maximum of 3 h. Ensembles 1 and 2 consisted of the CWIS in addition to
      minimal and maximal likely undergarment insulations, respectively. Open sea field
      trials (water temperature = 13.8 +/- 0.7 degree C; Beaufort wind state = 0-4; Sea
      state = 0-2) were conducted for a maximum of 2 h, with subjects wearing ensemble
      two and remaining strike aircrew apparel (ensemble three). Analysis of rectal
      temperature (Tre) changes permitted calculation of time to hypothermia (t35) and
      the survival estimate of 34 degrees C (t34). Mean (+/- SEM) t35 was 78 +/- 11 (n
      = 6), 187 +/- 20 (n = 5, p < 0.05) and 98 +/- 5 min (n = 3) for ensembles one,
      two and three, respectively. Mean t34 was 96 +/- 15, 259 +/- 31 (p < 0.05), and
      119 +/- 5 min, respectively. Immersed insulations of ensembles one and two were
      0.035 +/- 0.002 and 0.150 +/- 0.015 degree C.m2.W-1, respectively. Thus, the
      difference between minimal and maximal operational insulation was a 4.3-fold
      increase in insulation, which facilitated a 2.7-fold increase in mean t34. The
      thermal protection afforded by the CWIS during field trials was not sufficient to
      ensure survival for the 12-h expected rescue time.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7646403
TI  - The relationship of diet to airsickness.
AB  - This descriptive, correlational study examined meal frequencies and dietary
      intakes as they related to airsickness in a population of novice civilian pilots.
      Food and nutrient intakes and dietary patterns of pilots prior to flight were
      measured for association with airsickness. A 24-h dietary recall was used in
      recording dietary intake and meal frequencies during a typical flight day.
      Correlation analysis was used to determine relationships between dietary intake
      and airsickness. Of the female pilots, 75% experienced airsickness; and 24% of
      the male pilots experienced it. Female pilots' mean 24 h dietary intakes of
      vitamins A, C, and iron were low. The findings indicate eating high sodium foods
      (r = 0.33, p = 0.02) such as preserved meats, corn chips and potato chips, and
      eating foods high in thiamin (r = 0.35, p = 0.01) like pork, beef, eggs, or fish
      correlated significantly with increased airsickness. Consumption of foods high in
      protein such as milk products, cheeses and preserved meat by the males correlated
      significantly (r = 0.28, p = 0.05) with increased airsickness. The frequency of
      meals eaten during the day also correlated with increased airsickness. Of the
      airsick pilots, 75% consumed three or more meals in the previous 24 h, as
      compared to 41% of the nonairsick pilots. Higher density foods (more
      kilocalories) also increased the airsickness occurrences of both the male and
      female pilots.

PMID- 7646404
TI  - Characteristics of the venous hemodynamics of the leg under simulated
      weightlessness: effects of physical exercise as countermeasure.
AB  - In order to test the hypothesis that increases in calf venous distensibility in
      microgravity are partly due to the changes affecting the surrounding skeletal
      muscles (muscular atrophy), 12 healthy volunteers were exposed for 28 d to
      microgravity simulated by -6 degrees head-down bed rest. Half these subjects were
      exposed to countermeasures during bed rest: a) repeated LBNP (Lower Body Negative
      Pressure) sequences starting on the 15th d with one 15 min sequence at -35 mb,
      every other day from the 15th until the 21st d, and then every day until the end
      of bed rest; b) physical training including isotonic type exercise and isometric
      or isokinetic work by all muscle mass of upper and lower limbs (from the 8th
      until the 28th d). The other six subjects forming the control group were not
      subjected to any countermeasure. Calf venous hemodynamics were determined by
      mercury strain gauge plethysmography with venous occlusion. Distensibility (delta
      Vmax) and venous emptying (venous outflow at the 6th s of emptying: VO6, half
      emptying time: T1/2, maximum venous outflow (MVO) could also be measured. Nuclear
      magnetic resonance (NMR) was used to study changes in volume of calf muscles.
      Plethysmographic measurements made for each subject prior to, during (once a
      week), and after bed rest show a parallel increase in calf venous distensibility
      in both groups of subjects until the 20th d of bed rest. Filling and emptying
      times then tended to stabilize in the group treated with countermeasures (group
      CM) whereas high venous distensibility was observed until the end of bed rest and
      5 d thereafter in the control group (group C).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7646405
TI  - Effects of lags on human operator transfer functions with head-coupled systems.
AB  - The effects of operator learning and target velocity on head tracking performance
      with and without lags has been studied. Five lags (0, 40, 80, 120, 160 ms)
      between head movement and target image movement, and three target velocities (2,
      3.5, 5 degrees.s-1 r.m.s.) were investigated with eight male subjects and band
      limited random target motions. Head tracking transfer functions, tracking error
      spectra, mean radial tracking error, and subjective difficulty ratings were
      obtained. Head tracking performance was significantly degraded by lags greater
      than, or equal to, 40 ms (in addition to a system lag of 40 ms). Both the input
      correlated tracking error and the uncorrelated tracking error increased with
      increasing lag. No significant improvement in head tracking performance was found
      through practice with an 80-ms lag. As the lag increased, operators increased
      their gains at frequencies above about 0.5 Hz and reduced their phase lags at low
      frequencies (about 0.1 Hz) but failed to fully compensate for the increased
      display lag. The increased human operator gain was associated with increased
      operator phase lag at higher frequencies (above 0.5 Hz). To improve head tracking
      performance in the presence of lags, a lag compensation technique is needed to
      prevent undesirable changes in tracking strategy.

PMID- 7646406
TI  - Blood volume and erythropoiesis in the rat during spaceflight.
AB  - A decreased red blood cell mass (RBCM) and plasma volume (PV) have been
      consistently found in humans after return from spaceflight. Rats flown on the
      Spacelab Life Sciences-1 mission were studied to assess changes in RBCM, PV,
      erythropoiesis, and iron economy. The RBCM and PV increased in both ground
      control and flight animals as expected for growing rats. However on landing day,
      both the RBCM and PV, when normalized for body mass, were significantly decreased
      in the spaceflight animals. During an 8-d postflight observation period, iron
      incorporation into circulating red blood cells was diminished in the flight
      animals. During the first 4 d postflight, increases in reticulocyte counts were
      significantly smaller in the flight than the control animals. Fewer
      erythropoietin-responsive progenitor cells were recovered from the bone marrow of
      flight animals after landing than control rats. Serum erythropoietin (EPO) levels
      were the same in both groups. Thus, rats subjected to a 9-d spaceflight had less
      increase in RBCM than controls and diminished erythropoiesis during an 8-d post
      spaceflight observation period. The rat, like humans, appears to require a
      smaller blood volume in microgravity.

PMID- 7646407
TI  - No detectable bioeffects following acute exposure to high peak power ultra-wide
      band electromagnetic radiation in rats.
AB  - A wide range assessment of the possible bioeffects of an acute exposure to high
      peak power ultra-wide band (UWB) electromagnetic radiation was performed in rats.
      The UWB-exposure consisted of 2 min of pulsed (frequency: 60 Hz, pulse width: 5
      10 ns) UWB (bandwidth: 0.25-2.50 GHz) electromagnetic radiation. Rats were
      examined using one of the following: 1) a functional observational battery (FOB);
      2) a swimming performance test; 3) a complete panel of blood chemistries; or 4)
      determination of the expression of the c-fos protein in immunohistologically
      stained sections of the brain. No significant differences were found between UWB-
      or sham-exposed rats on any of the measured parameters.

PMID- 7646408
TI  - Self-tonometry under microgravity conditions.
AB  - Microgravity leads to a "fluid shift" towards the upper parts of the body and,
      therefore, to a rise of the intraocular pressure. Parabolic flights have also
      demonstrated some rise of the intraocular pressure. During the first German
      Spacelab mission D1, changes of the intraocular pressure were investigated for
      the first time in space. The first pressure readings were obtained 44 min after
      entering microgravity and showed a pressure rise of 20 to 25% compared to the
      baseline data. To get earlier measurements in microgravity a fully automatic self
      tonometer was developed which functioned independent of position and
      microgravity. It was used during an 8-d manned space mission in March 1992.
      Measurements of the intraocular pressure have been performed 16 min after
      reaching microgravity. The pressure readings revealed a 92% rise of the
      intraocular pressure compared to the daytime-correlated baseline data on Earth.

PMID- 7646409
TI  - Circadian rhythm desynchronosis in military deployments: a review of current
      strategies.
AB  - The combined problems of changing work schedules and work places are not uncommon
      in military operations. For example, during the Persian Gulf War, many military
      units underwent short notice transmeridian deployment with immediate commencement
      of 24-h operations upon arrival. Some of these individuals likely suffered from
      circadian desynchronosis, blunting their effectiveness. The United States Air
      Force approved limited use of one short acting hypnotic medication to assist
      aircrew sleep disorders in the operational theater and, until recently, one
      stimulant medication to enhance alertness. Multiple theoretical strategies for
      circadian rhythm management are available. However, many U.S. Air Force flight
      surgeons are not trained on how best to use medications in combination with other
      circadian rhythm strategies. We present a condensed review of current human
      circadian rhythm coping strategies pertinent to military operations.

PMID- 7646410
TI  - Spatial disorientation-implicated accidents in Canadian forces, 1982-92.
AB  - In a recent survey of CF18 aircrew human factors, 44% of pilots reported
      experience with spatial disorientation (SD), of whom 10% had experienced more
      than 3 episodes. In order to investigate further, we have completed a
      retrospective study of SD-implicated category A accidents (where an aircraft is
      destroyed, declared missing, or damaged beyond economic repair) in the Canadian
      Forces (CF) during 1982-92. An overview of all SD occurrences (including
      accidents and incidents) across aircraft types is also presented. Information was
      gathered concerning the genesis and severity of disorientation so that research
      effort and pilot training could be appropriately implemented. Mishap
      investigation summaries involving category A accidents where SD was implicated
      were obtained from the CF Directorate of Flight Safety and reviewed. We also
      examined in detail the Board of Inquiry Reports of these accidents. The role of
      disorientation in these accidents was assessed. There were 62 category A
      accidents between 1982-92 and, in 14, SD had been assigned as a possible cause
      factor in the accident records. When divided into the categories of Recognized SD
      (RSD), Unrecognized SD (USD), and Incapacitating SD (ISD), all but two fell into
      the category of USD (the pilots were unaware of the disorientation). Of the SD
      accidents, 11 involved a total loss of 24 lives. The majority of the accidents
      happened during the day, and pilots' cumulative flying experience did not appear
      to be a significant factor. According to our assessment, there were two episodes
      of vestibular origin, involving the somatogravic illusion. Three episodes of
      disorientation occurred over frozen lakes, one over glassy water, and one over
      ocean.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7646411
TI  - Considerations for human exposure standards for fast-rise-time high-peak-power
      electromagnetic pulses.
AB  - Development of new emitter systems capable of producing high-peak-power
      electromagnetic pulses with very fast rise times and narrow pulse widths is
      continuing. Such directed energy weapons systems will be used in the future to
      defeat electronically vulnerable targets. Human exposures to these pulses can be
      expected during testing and operations. Development of these technologies for
      radar and communications purposes has the potential for wider environmental
      exposure, as well. Current IEEE C95.1-1991 human exposure guidelines do not
      specifically address these types of pulses, though limits are stated for pulsed
      emissions. The process for developing standards includes an evaluation of the
      relevant bioeffects data base. A recommendation has been made that human exposure
      to ultrashort electromagnetic pulses that engender electromagnetic transients,
      called precursor waves, should be avoided. Studies that purport to show the
      potential for tissue damage induced by such pulses were described. The studies
      cited in support of the recommendation were not relevant to the issues of tissue
      damage by propagated pulses. A number of investigations are cited in this review
      that directly address the biological effects of electromagnetic pulses. These
      studies have not shown evidence of tissue damage as a result of exposure to high
      peak-power pulsed microwaves. It is our opinion that the current guidelines are
      sufficiently protective for human exposure to these pulses.

PMID- 7646412
TI  - Naval flight deck injuries: a review of Naval Safety Center data, 1977-91.
AB  - A comprehensive review of injuries sustained by personnel working on naval flight
      decks between January 1977 and December 1991 was conducted using database records
      maintained at the U.S. Naval Safety Center, Norfolk, VA. Data included all
      fatalities, permanent total disabilities, permanent partial disabilities, and
      major injuries resulting in 5 or more lost work days. Injuries were coded using
      ICD-9-CM codes for analysis. A total of 918 flight deck personnel were reported
      injured during this 15-yr period, including 43 fatalities, 5 permanent total
      disabilities, 42 permanent partial disabilities, and 828 major injuries. Of the
      non-fatalities, a plethora of fractures, traumatic amputations, major
      lacerations, dislocations, contusions, concussions, burns, crushing injuries,
      sprains, and strains were reported. Nearly all naval platforms with a flight deck
      reported an injury. While an average of 51 injuries per 100,000 aircraft
      recoveries were reported annually on aircraft carriers from 1977-86, a marked
      reduction to a rate of roughly 30 injuries was observed annually from 1987-90.
      What makes injuries sustained on the flight deck particularly disconcerting is
      that over 90% can be attributed to human causal factors.

PMID- 7646413
TI  - Desert Storm nursing.

PMID- 7646415
TI  - Coronary microcirculation: autoregulation and metabolic control.
AB  - The majority of studies examining the regulation of coronary blood flow and
      vascular resistance have considered the coronary circulation as being composed of
      large conduit vessels and resistance vessels. Recently, it has become apparent
      that regulation of coronary microvascular resistance is not distributed
      uniformly, but varies across different segments or microdomains of the
      vasculature. Generally, small arterioles, those less than 100 microns in
      diameter, respond differently than larger arterioles and small arteries. There
      are major differences in the level of autoregulatory control, myogenic control,
      endothelial modulation and control by metabolic factors across these various
      microvascular domains. There are also transmural variations which may account for
      some of the differences in coronary blood observed between epicardial and
      endocardial regions. In addition, interactions between these various regulatory
      mechanisms further complicate the understanding of coronary microvascular
      regulation. Importantly however, it may be these complex interactions and
      heterogeneous regulatory mechanisms which allow for adequate perfusion of the
      myocardium under an extreme range of metabolic conditions. This segmental
      distribution of regulation suggests an integrative hypothesis of regulation
      whereby a variety of mechanisms play a role in the overall response.

PMID- 7646414
TI  - Heterogeneity of myocardial blood flow.
AB  - Myocardial blood flow is heterogeneous, whether considered by chamber, by layers
      of the ventricular walls, or by microregions within layers. There is also
      variability of myocardial flow reserve, particularly in layers and microregions,
      even when the heart is arrested. The variability of flow during arrest may be
      associated with the resistance pathways to each region, but the variability of
      flows in the beating heart with vascular tone is probably due to regional
      differences in work and thus oxygen demand. Heterogeneity by layer may be
      responsible for the subendocardial ischemia that is common to many forms of heart
      disease. Microheterogeneity may account for the patchy necrosis that occurs with
      chronic ischemia.

PMID- 7646416
TI  - Endothelial control of coronary flow in perfused guinea pig heart.
AB  - In perfused isolated guinea pig hearts reactive hyperemia (RH) was induced by
      occlusion of coronary flow for periods ranging from 1-60 s. RH was hampered by
      100-60% in the presence of an inhibitor of NO synthase, NG-nitro-L-arginine (100
      microM) and, to a lesser extent (up to 35%), by an antagonist of adenosine
      receptors, 8-phenyltheophylline (10 microM). An inhibitor of PGH synthase,
      indomethacin (5 microM), did not affect RH. During RH the heart generated
      prostacyclin, nitric oxide, and adenosine as indicated by the appearance of 6
      keto-PGF1 alpha, cyclic GMP, urate, inosine, hypoxanthine and xanthine in the
      perfusate. Out of these factors only NO and adenosine were responsible for RH. NO
      was responsible for RH which was evoked by short-term (1-10s) coronary occlusion,
      whereas concurrent efforts of NO and adenosine were required to maintain RH that
      followed longer (20-60s) periods of interruption of coronary inflow. Thus, in the
      investigated system nitric oxide and adenosine but not prostacyclin can be
      considered as the mediators of myocardial reactive hyperemia.

PMID- 7646418
TI  - Ultrastructural characteristics of cellular reaction after experimentally induced
      lesions in the arterial vessel.
AB  - Restenosis after angioplasty occurs with an incidence of 20-50% and remains a
      major drawback. Certain randomized studies suggest that a bigger post-angioplasty
      lumen predicts a better long-term outcome. Conversely other studies showed a
      better outcome with limited injury. The present study aimed to investigate the
      depth of the lesion and relate this to cellular alterations after graded vascular
      injury. METHOD: Vessel segments of 30 pigs underwent injury using a directional
      atherectomy catheter. Vessels were assigned according to the extent of injury to
      Group 1 (intima lesion) or Group 2 (media injury). 2 hours to 7 days after
      injury, 68 arteries showing 41 intimal and 27 media lacerations were excised and
      processed for histology and transmission electron microscopy. RESULTS:
      Immediately after injury, thrombus formation was found at the site of the altered
      segment. A marked, transient infiltration of polymorphonuclear leukocytes (PMN)
      occurred only if the media was lacerated, starting within the first hours and
      increasing up until the 12 hours time point. The cellular infiltration was
      followed by a transformation of contractile myocytes to a synthetic subtype. The
      ratio of myofilaments to organelles decreased. A pronounced myoproliferative
      response was found in Group 2 after 7 days (p < 0.01), whereas only moderate
      tissue hyperplasia was seen in Group 1. CONCLUSION: The data presented provide
      evidence that the cellular alteration of injured vessels begins immediately.
      Subsequent to an initial temporary PMN infiltration, an activation of local
      myocytes occurs at a very early stage. In particular, a myoproliferative response
      was found only after deep injury with rupture of the internal elastic lamina.

PMID- 7646417
TI  - Neuronal control of coronary blood flow.
AB  - Controversies on acetylcholine-induced increases or decreases in coronary blood
      flow arise from obvious species differences, the role of endothelium in mediating
      vascular smooth muscle responses, and the marked negative chronotropic and
      inotropic effects of acetylcholine. In man, there appears to be a predominant
      dilation of intact epicardial coronary arteries and a constriction of
      artherosclerotic segments. However, at present there is no evidence for a vagal
      initiation of myocardial ischemia. Coronary vascular beta-adrenergic receptors
      mediate dilation, but appear to be functionally insignificant during sympathetic
      activation. The beta-adrenergic mechanism contributing to myocardial ischemia are
      indirect, mediated by a tachycardia-related redistribution of blood flow away
      from the ischemic myocardium. alpha-Adrenergic receptors mediating epicardial
      coronary artery constriction in experimental studies appear not to be responsible
      for the initiation of ischemia in patients with angina at rest. However, alpha
      adrenergic constriction of coronary resistance vessels resulting in the
      precipitation of post-stenotic myocardial ischemia was demonstrated in
      experimental studies and recently confirmed in patients with effort angina. Non
      adrenergic, non-cholinergic neurotransmitters exist; however, their role in
      regulating coronary blood flow remains entirely unclear.

PMID- 7646419
TI  - Mechanisms of ergonovine-induced hyperconstriction of coronary artery after x-ray
      irradiation in pigs.
AB  - Mechanisms of ergonovine-induced coronary hyperconstriction were examined in vivo
      and in vitro in miniature pigs. To provoke coronary hyperconstriction, the
      endothelium of a segment of a major branch of the left coronary artery was
      denuded in 19 Gottingen miniature pigs (4 to 6 months of age). In Group I (n =
      12), the denuded site of the coronary artery was selectively irradiated with 15Gy
      of x-ray twice, 3 and 4 months after endothelial denudation. The remaining 7 pigs
      were not irradiated (Group II). The vasoconstrictive effect of intracoronary
      administration of ergonovine (1 to 1000 microgram) was examined angiographically
      3 months (just before irradiation in group I) and 5 months after denudation in
      the two groups. After the angiographical study, the vessels were isolated and
      isometric tensions were measured in an organ chamber. In the in vivo studies,
      ergonovine-induced vasoconstriction at the denuded and x-ray irradiated site in
      Group I was significantly greater than that at the control site or that at the
      denuded site in Group II. Pretreatments with serotonin receptor blockers
      (ketanserin or methysergide) significantly attenuated ergonovine-induced
      hyperconstriction, while an alpha-adrenergic receptor blocker (prazosin) did not
      (% inhibition; ketanserin 74 +/- 9%, p < 0.01, methysergide 60 +/- 10%, p < 0.01,
      prazosin 9 +/- 5%, NS). In the in vitro studies, ergonovine produced
      significantly greater tension at the denuded and x-ray irradiated site (Group I)
      than at the control site or at the denuded site (Group II). Ergonovine-induced
      endothelium-dependent relaxation was impaired at the denuded site in both groups
      to a similar extent. These results suggest that ergonovine-induced
      hyperconstriction at the denuded and x-ray irradiated coronary artery resulted
      mainly from the hyperreactivity of medial smooth muscle mediated by serotonin
      receptors.

PMID- 7646420
TI  - Effect of adenosine deaminase inhibition with pentostatin on myocardial stunning
      in dogs.
AB  - Pentostatin (2-deoxycoformycin) is a potent inhibitor of adenosine deaminase and
      has been demonstrated to augment endogenous adenosine levels during regional and
      global myocardial ischemia. Based on the rationale that increasing endogenous
      adenosine during ischemia may be cardioprotective, the objective of this study
      was to determine if adenosine deaminase inhibition with pentostatin could improve
      postischemic contractile dysfunction (stunning) in open-chest anesthetized dogs.
      All animals underwent 15 min of coronary occlusion followed by 3 h of reperfusion
      preceded by an intravenous bolus of either 0.2 mg/kg of pentostatin (n = 8) or
      saline (n = 7). Sonomicrometers were placed in the ischemic area and were used to
      measure systolic wall thickening before, during, and after occlusion of the left
      anterior descending artery. Myocardial blood flow was measured with tracer
      labeled microspheres at baseline, 10 min of occlusion and at 1 h of reperfusion.
      Both groups were equally dyskinetic during occlusion (-21 +/- 5% of baseline
      thickening in the controls and -28 +/- 8% in the pentostatin group). The
      pentostatin group, however, demonstrated better contractile function at all time
      points during reperfusion, which was significantly different from the control
      group at 3 h of reperfusion. The improvement in regional function in the
      pentostatin group was not due to significant disparities in hemodynamic
      variables, size of the region at risk, or in collateral blood flow. These results
      indicate that pentostatin can ameliorate the severity of myocardial stunning, an
      effect we propose is due to increasing endogenous levels of adenosine during the
      ischemic interval. Although significant improvement was detected with
      pentostatin, the improvement was modest compared to controls, suggesting that the
      utility of inhibiting adenosine deaminase to modify regional mechanical stunning
      is limited.

PMID- 7646421
TI  - ATP-sensitive potassium channels and myocardial preconditioning.
AB  - The ATP-sensitive potassium channel (KATP) has been shown to serve an endogenous
      cardioprotective role in a number of experimental models of myocardial stunning
      and infarction. More importantly, a majority of evidence has also been obtained
      which suggests that the KATP channel may be intimately involved in both
      triggering and maintaining the cardioprotection afforded by the phenomenon of
      ischemic preconditioning particularly in large animal models such as dogs and
      pigs. Although the evidence for an involvement of KATP in ischemic pre
      conditioning is equivocal in smaller animal species such as rabbits and rats,
      activation of this channel by KATP channel openers produces cardioprotection in
      all species studied. Whether this channel is an important mediator of ischemic
      preconditioning in all animal species including man and the mechanism by which
      this cardioprotective effect is obtained await further experimental studies.
      Nevertheless, the use of selective potassium channel openers to mimic
      preconditioning in selected clinical settings may be a desirable future
      therapeutic goal.

PMID- 7646423
TI  - [Infectivity of Campylobacter jejuni and Campylobacter coli in chickens].
AB  - The infectivity of four Campylobacter (C.) jejuni strains and one C. coli strain
      was evaluated by the reisolation rate from cloacal swabs after oral infection of
      chickens at four weeks of age. One strain did not colonize the digestive tract,
      another infected only a part of the experimental group and a third was excreted
      at a lower percentage in the first two weeks p.i. compared to the other two
      strains. In correlation to age, the excretion rate was highest in 7-week-old
      birds. In groups of 4 and 10-week-old chickens, the peak of the excretion rate
      appeared slightly delayed and on average, the excretion was lowest in 10-week-old
      individuals. A high correlation was found between the isolation rate of
      Campylobacters from cloacal swabs and from caecal contents.

PMID- 7646422
TI  - Mechanical determinants of myocardial perfusion.

PMID- 7646424
TI  - [Ionized calcium and total calcium in the cat].
AB  - The concentrations of total calcium (Catot), of the biologically active ionized
      calcium fraction (Caion), and of albumin were measured from the plasma of 92
      healthy cats and 154 patients. Only a moderate correlation existed between the
      concentrations of Catot and Caion (r = 0.718), so that the concentration of Catot
      reflects the calcium homeostasis only to a limited extent. An essential reason
      for this lies in the distinct dependence of the Catot on the albumin
      concentration (r = 0.628). On the basis of the 2.5 and 97.5% quantile of the
      healthy cats, the reference range for Caion was 1.15-1.37 mmol/l (age group > or
      = 6 months, < 2 years: 1.23-1.38; > or = 2 years: 1.14-1.35 mmol/l), for Catot
      2.49-2.87 mmol/l (2.52-2.92; 2.35-2.81 mmol/l) and the fraction of Caion of the
      Catot 44.5-50.6%. Like the Catot, the Caion also showed no dependence on the sex.
      Against that, the distinct dependence on age of these two parameters (p < 0.001),
      which expresses the decreasing Ca concentration in older animals, should be
      regarded for a discriminating interpretation of measurement results.

PMID- 7646425
TI  - [Demonstration of cells of the mononuclear phagocyte system of the cat using
      enzyme and immunohistochemistry methods].
AB  - The suitability of enzyme- and immunohistochemical methods for the demonstration
      of mononuclear phagocytes in cats is treated. The activity of nonspecific
      esterases with the substrates alpha-naphthyl-acetate, alpha-naphthyl-butyrate and
      naphthol-AS-acetate, and of acid phosphatases with the substrate naphthol-AS-BI
      phosphate is demonstrated in paraffin and plastic sections of the liver, lungs,
      spleen and lymph node. Even with modified methods, only slight reactions were
      obtained in cat tissues compared to sections of rat organs. Four antibodies
      against human macrophage antigens were tested in paraffin sections. Only the
      antibody against alpha-1-antichymotrypsin showed no cross-reactions in the cat.
      Neutrophilic granulocytes reacted strongly, macrophages only very slight with the
      anti-lysozyme-antisera and the monoclonal antibody MAC 387. Apart from some
      macrophages, interdigitating reticulum cells, B- and T-lymphocytes in the cat
      were stained by the anti HLA-DR antibody TAL-1B5.

PMID- 7646426
TI  - [Lactoperoxidase activity and thiocyanate content of milk from cows with mastitis
      in different lactation stages].
AB  - During three lactational periods (start, middle and end of lactation) of 35 milk
      cows suffering from mastitis and compared with 34 healthy milk cows of comparable
      milk production the activity of lactoperoxidase (LPO) and the SCN-content of the
      milk in each udder quarter were determined. Both components showed no alterations
      in the subclinical form of the disease. There exists a decrease of the LPO
      activity in the secretion of ill udder quarters, which will be distinct only in
      the individual animal and a strong increase of the SCN-content, which is also
      significant in comparison with the milk of healthy cows.

PMID- 7646427
TI  - [Thiocyanate content in blood plasma, udder lymph and milk from healthy cows and
      cows with mastitis].
AB  - After storage for more than one year the SCN(-)-content of udder lymph was not
      changed seriously, but in blood serum and mainly in milk, there is an evident
      decrease. In lactational cows with healthy udders the SCN(-)-content of blood
      plasma is higher than in milk (in average twice). There is no difference of the
      SCN(-)-content of the four udder parts of healthy cows. Decrease of milk
      production (10. to 13. lactational month) causes an increase of the SCN(-)
      content of the milk, it is not changed in subclinical mastitis. In lactational
      cows with healthy udders the SCN(-)-content of udder lymph is nearly triple
      higher in average than in milk of the corresponding quarter of the udder. The
      existence of a common compartment of SCN- in blood and udder lymph is assumed,
      which is separated from them of the milk by the blood udder barrier.

PMID- 7646428
TI  - [Discussion of the article in Berliner und Munchener Tierarztlicher Wochenschrift
      107: 150-176 (1994)].

PMID- 7646429
TI  - The GABAA receptors.

PMID- 7646430
TI  - The role of cysteine in the alteration of bovine liver dihydrodiol dehydrogenase
      3 activity.
AB  - Bovine liver NADP(+)-dependent dihydrodiol dehydrogenase (DD3) is extremely
      sensitive to SH reagents such as N-ethylmaleimide (NEM) and 5,5'-dithiobis(2
      nitrobenzoic acid). NEM produced time- and concentration-dependent inactivation
      of DD3 in a pseudo-first-order reaction manner. This inactivation was prevented
      by NADP+, 3-acetylpyridine-adenine dinucleotide phosphate, 2',5'-ADP and 2'-AMP
      but not by substrates, NAD+, nicotinamide mononucleotide or 5'-ADP.DD3 was
      absorbed by an affinity column of thiopropyl-Sepharose 6B, but enzyme incubated
      with both NEM and NADP+ was not. Moreover, one [14C]NEM molecule was incorporated
      into a cysteine of DD3 in the presence, and two cysteines of DD3 in the absence,
      of NADP+. These results suggested that two cysteine residues were modified per
      enzyme molecule by NEM, one was protected by NADP+ and the other had no
      significant function for the enzyme activity. Two radiolabelled peptides (P1 and
      P2) produced by the digestion with lysyl endopeptidase of [14C]NEM-modified DD3
      could be separated by reverse-phase HPLC. P1, which was radiolabelled by [14C]NEM
      only in the absence of NADP+, showed the following sequence; H2N-Tyr-Lys-Pro-Val
      Xaa-Asn-Gln-Val-Glu- NEM.Cys-His-Pro-Tyr-Phe-Asn-Gln-Ser-Lys-COOH (Xaa indicates
      a possible cysteine residue). This sequence was very similar to that of rat liver
      3 alpha-hydroxysteroid/dihydrodiol dehydrogenase (3 alpha-HSD/DD) (residues 184
      to 201) and was also highly conserved in the aldo-keto reductase superfamily. The
      sequence of P2, which had radioactivity in both the absence and presence of
      NADP+, also contained an NEM-modified cysteine and was similar in sequence to the
      regions located in loop A of rat 3 alpha-HSD/DD. The present study suggests that
      P1, which may have a cysteine residue corresponding to Cys-193 of rat 3 alpha
      HSD/DD, functions in the alteration of DD3 activity depending on the modulation
      of NADP(+)-binding ability through a thiol/disulphide exchange reaction similar
      to that of rat 3 alpha-HSD/DD shown in our previous results; while P2, which may
      have a cysteine residue corresponding to Cys-145 of rat 3 alpha-HSD/DD, may be
      located near the surface of the enzyme molecule.

PMID- 7646431
TI  - Active site labelling of inositol 1,4,5-trisphosphate 3-kinase A by
      phenylglyoxal.
AB  - Chemical modification by phenylglyoxal, an arginine-specific reagent, of both
      native and recombinant rat brain inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] 3
      kinase A was accompanied by irreversible inhibition of enzyme activity. This
      effect was prevented in the presence of the substrate ATP but not Ins(1,4,5)P3.
      The modification reaction obeyed pseudo-first-order rate kinetics. Complete
      inhibition of activity corresponded to incorporation of 1.2 mol of phenylglyoxal
      per mol of protein. A single [14C]phenylglyoxal-modified peptide was isolated
      following alpha-chymotrypsin digestion of the radiolabelled Ins(1,4,5)P3 3-kinase
      and reverse-phase HPLC. ATP prevented the incorporation of radioactivity to this
      peptide. The peptide sequence (i.e. QWREGISSSTTL) corresponded to amino acids 315
      to 326 of rat brain Ins(1,4,5)P3 3-kinase A. An estimate of the radioactivity of
      the different phenylthiohydantoin amino acid derivative showed the modified amino
      acid to be Arg-317. The data directly identify a reactive arginine residue as
      part of the ATP-binding site. Arg-317 is located within a sequence segment which
      is conserved among the catalytic domain of Ins(1,4,5)P3 3-kinase isoenzymes A and
      B in human and rat species.

PMID- 7646432
TI  - Microsomal triglyceride transfer protein activity remains unchanged in rat livers
      under conditions of altered very-low-density lipoprotein secretion.
AB  - Microsomal triglyceride transfer protein (MTP) is a heterodimeric protein
      consisting of a unique 97 kDa subunit and protein disulphide isomerase, that
      mediates the transfer of lipid between membranes and nascent lipoproteins.
      Mutations in the gene encoding the 97 kDa subunit of the protein cause the rare
      autosomal recessive disorder abetalipoproteinaemia. Recent findings in cultured
      cells indicate that the 5' promoter region contains an insulin-responsive
      element, suggesting that the gene is responsive to insulin regulation. In this
      study we examined two cases where very-low-density lipoprotein (VLDL) secretion
      is markedly reduced: the streptozotocin-diabetic rat and 10-day-old suckling
      rats. In both cases MTP activity was unaltered compared with that in control
      animals. Equal levels of MTP were also apparent in the livers of all groups of
      animals, as measured by immunoblotting with an anti-MTP antiserum. These findings
      indicate that factors other than MTP activity are responsible for the reduction
      in hepatic VLDL triglyceride secretion observed in the suckling and diabetic
      animals.

PMID- 7646433
TI  - A subunit interface mutant of yeast pyruvate kinase requires the allosteric
      activator fructose 1,6-bisphosphate for activity.
AB  - A variant form of yeast pyruvate kinase (EC 2.7.1.40) with Ser-384 mutated to
      proline has been engineered in order to study the allosteric properties of this
      enzyme. Both the mutant and wild-type enzymes were overexpressed in a strain of
      yeast in which the genomic copy of the pyruvate kinase gene had been disrupted by
      an insertion of the Ura3 gene. Both enzymes were purified to homogeneity and
      their kinetic properties characterized. The wild-type enzyme displays sigmoid
      kinetics with respect to phosphoenolpyruvate (PEP) concentration, and is
      activated by the allosteric effect fructose 1,6-bisphosphate with concomitant
      reduction in co-operativity. In contrast, the mutant was found to be dependent on
      the presence of the effector for catalytic activity and was inactive in its
      absence. The fully activated mutant enzyme had a kcat. 1.6 times greater than
      that of the wild-type enzyme. The mutation introduced into the enzyme is in an
      intersubunit contact which is known to be critical for the allosteric properties
      of the enzyme, and is far removed from the active site. The major effect of the
      mutation seems to be to stabilize the low-affinity T state of the apoenzyme,
      although kcat. is also affected. The S0.5 for PEP and S0.5 for ADP of the wild
      type enzyme were 0.22 +/- 0.004 and 0.15 +/- 0.01 mM respectively (means +/-
      S.E.M.). In the activated mutant enzyme, these kinetic parameters increased to
      0.67 +/- 0.03 and 0.43 +/- 0.03 mM respectively. The cooperativity between ADP
      binding sites was altered in the mutant enzyme, with the Hill coefficient (h) for
      ADP increasing to 1.65 +/- 0.07 in the presence of the effector, compared with a
      value of 0.01 +/- 0.07 for the wild-type enzyme under the same conditions. CD
      spectroscopy revealed the secondary structure of the mutant enzyme to be little
      different from that of the wild-type enzyme, indicating that the two enzymes have
      similar secondary structures in solution. Precise tertiary and quaternary
      structures such as intersubunit and interdomain interactions may be modified. An
      improved purification procedure has been devised that allows large quantities of
      enzyme to be rapidly prepared.

PMID- 7646434
TI  - Ethanol inhibits insulin receptor substrate-1 tyrosine phosphorylation and
      insulin-stimulated neuronal thread protein gene expression.
AB  - Neuronal thread proteins (NTPs) are molecules that accumulate in the brains of
      patients with Alzheimer's disease, and may play a key role in both normal and
      neurodegenerative neuritic sprouting. In this investigation we determined whether
      NTP expression is up-regulated by insulin, an important neurotrophic factor that
      stimulates differentiation-associated neurite outgrowth, and studied the effects
      of ethanol, a known inhibitor of growth factor receptor tyrosine phosphorylation,
      on NTP expression and insulin-mediated signal transduction cascade in neuronal
      [primitive neuroectodermal tumour cell line 2; (PNET2)] cells. PNET2 cells were
      treated with 50 m-units/ml insulin in the presence or absence of 100 mM ethanol
      for 0.2-96 h, and cell proliferation and expression of NTP molecules were
      investigated by metabolic labelling, immunoprecipitation and immunohistochemical
      staining. Insulin stimulation resulted in an immediate increase in the levels of
      three (38, 18 and 15 kDa) of five NTP species (the others were of 26 and 21 kDa),
      followed by a decline in expression within 120 min; however, studies performed up
      to 96 h of culture demonstrated up-regulation by insulin of all five NTP species.
      Ethanol either abolished or severely muted the short- and long-term insulin
      mediated upregulation of NTP expression, and substantially reduced insulin
      mediated neuronal differentiation. The effects of ethanol on NTP gene expression
      were associated with impaired insulin-mediated tyrosine phosphorylation of both
      the insulin receptor beta subunit and the insulin receptor substrate-1 (IRS-1),
      resulting in decreased association of phosphatidylinositol 3-kinase with IRS-1.
      The findings suggest that ethanol may inhibit NTP expression associated with
      central nervous system neuronal differentiation by uncoupling the IRS-1-mediated
      insulin signal transduction pathway.

PMID- 7646435
TI  - Involvement of oxidants and oxidant-generating enzyme(s) in tumour-necrosis
      factor-alpha-mediated apoptosis: role for lipoxygenase pathway but not
      mitochondrial respiratory chain.
AB  - Cellular signalling by the inflammatory cytokine tumour necrosis factor alpha
      (TNF alpha) has been suggested to involve generation of low levels of reactive
      oxygen species (ROS). Certain antioxidants and metal chelators can inhibit
      cytotoxicity and gene expression in response to TNF alpha in numerous cell types.
      However, neither the source nor function of TNF alpha-induced oxidant generation
      is known. Using specific inhibitors, we ruled out involvement of several oxidant
      generating enzymes [cyclo-oxygenase (indomethacin), cytochrome P-450
      (metyrapone), nitric oxide synthase (NG-methyl-L-arginine), NADPH oxidase
      (iodonium diphenyl), xanthine oxidase (allopurinol), ribonucleotide reductase
      (hydroxyurea)] in TNF alpha-mediated apoptosis of the murine fibrosarcoma line,
      L929. We also demonstrated no role for mitochondrial-derived radicals/respiratory
      chain in the lytic pathway using specific inhibitors/uncouplers (rotenone, KCN,
      carboxin, fluoroacetate, antimycin, malonate, carbonyl cyanide p
      trifluoromethoxyphenylhydrazone) and chloramphenicol-derived respiration
      deficient cells. Significant ROS (H2O2, O2-.) generation was not observed in
      response to TNF alpha in L929 cells using four separate assays. Also, prevention
      of intracellular H2O2 removal by inhibition of catalase did not potentiate TNF
      alpha-mediated cell death. These data suggest that neither H2O2 nor O2-. plays a
      direct role in TNF alpha cytotoxicity. Finally, we suggest a central role for
      lipoxygenase in TNF alpha-mediated lysis. Three inhibitors of this radical
      generating signalling pathway, including an arachidonate analogue (5,8,11,14
      eicosatetraynoic acid), could protect cells against TNF alpha. The inhibitor
      nordihydroguaiaretic acid is also a radical scavenger, but it could not protect
      cells from ROS toxicity at concentrations that effectively prevented TNF alpha
      killing. Therefore protection by nordihydroguaiaretic acid cannot be due to
      scavenging of cytotoxic H2O or O2-.. The lipoxygenase product, (12S)
      hydroxyeicosatetraenoic acid, was also significantly protective. As this analogue
      can act as a substrate for certain lipoxygenases, this effect may be due to
      prevention of generation of physiological products.

PMID- 7646436
TI  - The effect of interleukin-1 on C-reactive protein expression in Hep3B cells is
      exerted at the transcriptional level.
AB  - The combination of interleukin 6 (IL-6) and interleukin 1 (IL-1) synergistically
      induces the human acute-phase reactant, C-reactive protein (CRP) in Hep3B cells.
      While previous studies have indicated that IL-6 induces transcription of CRP, the
      mode of action of IL-1 has not been clearly defined. It has been suggested that
      the effect of IL-1 might be post-transcriptional, exerted through the 5'
      untranslated region (5'-UTR). To evaluate the role of IL-1 in CRP gene
      expression, we studied the effects of interleukin-6 (IL-6) and interleukin-1 beta
      (IL-1 beta) on both the endogenous CRP gene and on transfected CRP-CAT constructs
      in Hep3B cells. In kinetic studies of the endogenous CRP gene, IL-1 beta alone
      had no effect on CRP mRNA levels, but when added to IL-6, synergistically
      enhanced both CRP mRNA levels and transcription, as determined by Northern-blot
      analyses and nuclear run-on studies. IL-6 alone and the combination of [IL-1 beta
      + IL-6] each induced increases in mRNA levels roughly comparable with observed
      increases in transcription. These findings indicate that the effect of IL-1 beta
      on CRP expression is exerted largely at the transcriptional level in this system.
      This conclusion was confirmed by studies in Hep3B cells transiently transfected
      with CRP-CAT constructs, each containing 157 bp of the CRP 5'-flanking region but
      differing in the length of the 5'-UTR from 104 bp to 3 bp. All constructs
      responded in the same way; IL-6, but not IL-1 beta, induced significant
      chloramphenicol acetyltransferase (CAT) expression which was synergistically
      enhanced 2- to 3-fold by IL-1 beta. These results indicate that IL-1 beta
      stimulates transcriptional events in the presence of IL-6 and that the upstream
      157 bases of the CRP promoter contain elements capable of both IL-6 induction and
      the synergistic effect of IL-1 beta on transcription.

PMID- 7646437
TI  - Hydrogen peroxide at low concentrations strongly enhances the inhibitory effect
      of nitric oxide on platelets.
AB  - Simultaneous application of NO and H2O2 to human platelets at physiologically
      relevant concentrations increased inhibition of platelet aggregation by NO almost
      100-fold. If NO and H2O2 were mixed before the addition to platelets, the
      inhibitory effect remained but still depended on the presence of NO. This
      suggested an enhanced sensitivity of the platelets to residual NO in the presence
      of H2O2. The inhibition by the NO/H2O2 mixture was not due to peroxynitrite and
      was only partly reversed by radical scavengers. The mechanism includes enhanced
      formation of cyclic GMP in response to NO in the presence of H2O2. H2O2 may play
      a positive physiological role by amplification and/or prolongation of the action
      of NO.

PMID- 7646438
TI  - Transcriptional promoter of the human alpha 1(V) collagen gene (COL5A1).
AB  - We have characterized the 5' region of the human alpha 1(V) collagen gene
      (COL5A1). The transcriptional promoter is shown to have a number of features
      characteristic of the promoters of 'housekeeping' and growth-control-related
      genes. It lacks obvious TATA and CAAT boxes, has multiple transcription start
      sites, has a high GC content, lies within a well-defined CpG island and has a
      number of consensus sites for the potential binding of transcription factor Sp1.
      This type of promoter structure, while unusual for a collagen gene, is consistent
      with the broad distribution of expression of COL5A1 and is reminiscent of the
      promoter structures of the genes encoding type VI collagen, which has a similarly
      broad distribution of expression. Stepwise deletion of COL5A1 5' sequences,
      placed upstream of a heterologous reporter gene, yielded a gradual decrease in
      promoter activity, indicating that the COL5A1 promoter is composed of an array of
      cis-acting elements. A minimal promoter region contained within the 212 bp
      immediately upstream of the major transcription start site contained no consensus
      sequences for the binding of known transcription factors, but gel mobility shift
      assays showed this region to bind nuclear factors, including Sp1, at a number of
      sites. The major transcription start site is flanked by an upstream 34-bp
      oligopurine/oligopyrimidine stretch, or 'GAGA' box, and a downstream 56-bp GAGA
      box which contains a 10-bp mirror repeat and is sensitive to cleavage with S1
      nuclease.

PMID- 7646439
TI  - Mechanisms of platelet activation by a stimulatory antibody: cross-linking of a
      novel platelet receptor for monoclonal antibody F11 with the Fc gamma RII
      receptor.
AB  - The mechanisms by which a stimulatory monoclonal antibody (mAb), called mAb F11,
      induces granular secretion and aggregation in human platelets have been
      characterized. Fab fragments of mAb F11, as well as an mAb directed against the
      platelet Fc gamma RII receptor (mAb IV.3) were found to inhibit mAb F11-induced
      platelet secretion and aggregation, indicating that the mAb F11 IgG molecule
      interacts with the Fc gamma RII receptor through its Fc domain and with its own
      antigen through its Fab domain. The mAb F11 recognized two platelet proteins of
      32 and 35 kDa on the platelet membrane surface, as identified by Western blot
      analysis. We purified both proteins from human platelet membranes using DEAE
      Sepharose chromatography followed by mAb F11 affinity chromatography. When added
      to platelet-rich plasma, the purified proteins dose-dependently inhibited mAb F11
      induced platelet aggregation. The purified protein preparation also competitively
      inhibited the binding of 125I-labelled mAb F11 to intact platelets. The N
      terminal 26 amino acid sequences of both the 32 and 35 kDa proteins were
      identical and contained a single unblocked serine in the N-terminal position.
      When digested with N-glycanase, the 32 and 35 kDa proteins were converted into a
      single approximately 29 kDa protein, indicating that these two proteins are
      derived from the same core protein but differ in their degree of glycosylation.
      Internal amino acid sequence analysis of the F11 antigen provided information
      concerning 68 amino acids and suggested two consensus phosphorylation sites for
      protein kinase C (PKC). The phosphorylation by PKC of the isolated F11 antigen
      was observed following stimulation by phorbol 12-myristate 13-acetate. Databank
      analysis of the N-terminal and internal amino acid sequences of the F11 antigen
      indicated that the N-terminal sequence exhibited the highest degree of similarity
      to the variable region of the alpha-chain of human T-cell receptors (TCR). In
      contrast, the F11 internal sequences did not exhibit any similarity to the TCR.
      Our results demonstrate that the F11 antigen is a novel platelet membrane surface
      glycoprotein which becomes cross-linked with the Fc gamma RII receptor when
      platelets are activated by the stimulatory mAb F11. These mechanisms may be
      relevant to the production of immune thrombocytopenia by platelet-activating
      antibodies.

PMID- 7646440
TI  - Phorbol 12-myristate 13-acetate-mediated signalling in murine bone marrow cells.
AB  - Phorbol 12-myristate 13-acetate (PMA)-mediated signalling was investigated in
      relation to the ability of murine (CBA) bone marrow cells to form colonies in
      vitro. Treatment of marrow cells with PMA did not influence the 1,2
      diacylglycerol or cyclic AMP concentrations, the intracellular Ca2+ concentration
      or phospholipase D activity. PMA increased particulate phospholipase A2 (PLA2)
      activity, lysophosphatidylcholine formation and arachidonic acid release from
      bone marrow cells; these effects were abolished when cells were pretreated with
      the putative PLA2 inhibitors heparin and mepacrine. While indomethacin and
      nordihydroguaiaretic acid inhibited either the cyclo-oxygenase or lipoxygenase
      pathway of arachidonic acid metabolism, as measured by their products
      prostaglandin E2 and leukotriene B4, they did not influence PMA-mediated PLA2
      activation or translocation of protein kinase C (PKC) from the soluble to the
      particulate fraction. Treatment of cells with PMA increased the amounts of
      membrane-bound alpha, beta, delta, epsilon and zeta isoforms of PKC in bone
      marrow cells. Pretreatment of cells with PLA2 inhibitors reduced the amount of
      membrane-bound PKC-zeta in unstimulated cells and diminished PMA-induced
      translocation of PKC-zeta to membranes without affecting other PKC isoforms. This
      effect could be overcome by exogenous addition of arachidonic acid, suggesting
      that PKC-zeta may operate downstream of the activated PLA2. On the other hand,
      wortmannin, an inhibitor of phosphatidylinositol 3-kinase, did not influence the
      amount of PKC-zeta associated with particulate fractions in control cells and
      could not abolish the PMA-mediated translocation of this isoform. Short-term
      exposure (45 min) of bone marrow cells to PMA, phorbol 12,13-dibutyrate or
      arachidonic acid increased the number of colonies formed over 7 days in a
      methylcellulose-based culture in vitro. The effects of PMA, but not those of
      arachidonic acid, could be prevented by putative PLA2 inhibitors. This suggests
      that PMA-mediated activation of conventional PKCs and novel PKCs leads to PLA2
      activation which, by releasing arachidonic acid from phospholipids, activates PKC
      zeta. This signalling pathway appears to be mitogenic for bone marrow cells.

PMID- 7646441
TI  - Stimulation of tissue-type plasminogen activator gene expression by sodium
      butyrate and trichostatin A in human endothelial cells involves histone
      acetylation.
AB  - We have previously shown that the pleiotropic agent sodium butyrate strongly
      stimulates tissue-type plasminogen activator (t-PA) expression in human umbilical
      vein endothelial cells (HUVEC). Here we provide the following evidence that the
      butyrate-induced t-PA expression in HUVEC involves histone H4 acetylation. (1) t
      PA induction by butyrate occurs at the transcriptional level and does not require
      new protein synthesis, indicating a direct effect. (2) t-PA induction by butyrate
      can be fully mimicked by a specific, structurally unrelated, histone deacetylase
      inhibitor, trichostatin A. (3) At optimally stimulatory conditions, a combination
      of butyrate and trichostatin A does not enhance t-PA production more than each of
      the compounds alone, indicating that both compounds act through a common
      regulatory mechanism. (4) Induction of t-PA transcription by butyrate and
      trichostatin A was found to be preceded by histone H4 acetylation; at suboptimal
      inducing concentrations of butyrate and trichostatin A, the degree of acetylation
      of histone H4 caused by each agent was similarly reduced. These results are
      consistent with a role for histone H4 acetylation in t-PA induction by butyrate
      in HUVEC.

PMID- 7646442
TI  - Equilibrium and pre-equilibrium fluorescence spectroscopic studies of the binding
      of a single-immunoglobulin-binding domain derived from protein G to the Fc
      fragment from human IgG1.
AB  - A single-immunoglobulin-binding protein based upon the C2 domain of Protein G
      from Streptococcus has been shown to bind tightly to the Fc fragment of IgG1. The
      binding interaction results in a decrease in the fluorescence intensity from the
      sole Trp residue (Trp-48) in this domain. This spectral change has been used to
      monitor the binding interactions between the two proteins using equilibrium and
      pre-equilibrium fluorescence spectroscopy. Comparison of the data from the two
      techniques suggests that a conformational change occurs after the initial
      formation of the complex. Mutagenesis studies have shown that the Trp residue is
      important for binding and that replacement by a Phe residue is important for
      binding and that replacement by a Phe residue leads to a 300-fold decrease in the
      affinity for Fc gamma 1. Determination of the rate constants kon and koff at
      different values of pH between 4.0 and 9.0 suggest that variations in Kd are
      mediated predominantly by changes in kon. Competition experiments between SpG1
      and a single-IgG-binding domain from Protein A from Staphylococcus aureus have
      been used to determine the affinity of the latter for Fc gamma 1.

PMID- 7646443
TI  - Effect of oxidized glutathione and temperature on inositol 1,4,5-trisphosphate
      binding in permeabilized hepatocytes.
AB  - The effect of oxidized glutathione (GSSG) on inositol 1,4,5-trisphosphate (IP3)
      binding and the activity of IP3-gated Ca2+ channels was examined in permeabilized
      hepatocytes. The permeability properties of the channel were measured by using
      Mn2+ quenching of compartmentalized fura-2 at 37 degrees C and at 4 degrees C for
      comparison with IP3-binding measurements. GSSG (2 mM) increased the IP3
      sensitivity of Mn2+ quenching, consistent with previous studies based on Ca(2+)
      release measurements [Renard, Seitz and Thomas (1992) Biochem. J. 284, 507-512].
      Measurements of [3H]IP3 binding were made at 4 degrees C after preincubation of
      permeabilized hepatocytes at 37 degrees C in the absence or presence of GSSG.
      Under these conditions GSSG stimulated IP3 binding by increasing the number of
      binding sites without changing the Kd. This effect was observed in the absence or
      presence of Ca2+, but was abolished when the preincubation with GSSG was carried
      out at 4 degrees C. Thimerosal also stimulated [3H]IP3 binding, but this effect
      was mediated both by an increase in the maximum number of binding sites and by a
      decrease in the Kd. The effects of thimerosal and GSSG were not additive. Further
      analysis of the effect of GSSG revealed that preincubation of permeabilized
      hepatocytes at 37 degrees C results in a progressive loss of [3H]IP3-binding
      sites that can be prevented and reversed by inclusion of GSSG. A parallel loss of
      IP3-sensitive Mn(2+)-quenchable stores was observed after incubation at 37
      degrees C, and this could also be reversed by adding back GSSG. The loss of IP3
      binding was not the result of IP3-receptor proteolysis, as judged by Western
      blotting of immunoreactive protein. The sensitivity of [3H]IP3 binding in
      permeabilized hepatocytes to varied ratios of GSSG and GSH suggests that the IP3
      receptor responds to an oxidized redox environment such as that found in the
      lumen of the endoplasmic reticulum. GSSG had no direct effect on the ligand
      binding activity of detergent-solubilized and partially purified IP3 receptors.
      We conclude that GSSG exerts an indirect effect on the IP3 receptors in
      permeabilized hepatocytes by preventing a temperature-dependent loss of IP3
      binding sites. We suggest that the hepatic IP3 receptors may interact with a
      thiol-disulphide oxidoreductase that utilizes GSSG as a substrate and prevents
      inappropriate unfolding of the ligand-binding domain occurring after incubation
      of the receptor at 37 degrees C in vitro.

PMID- 7646444
TI  - The mRNAs for cyclin A, c-myc and ribosomal proteins L4 and S6 are associated
      with cytoskeletal-bound polysomes in HepG2 cells.
AB  - Cytosolic, cytoskeleton and membrane fractions were extracted from HepG2 cells by
      a sequential detergent/salt extraction procedure. The cytosolic fraction
      contained 93% of the lactic dehydrogenase activity while the cytoskeleton
      fraction was enriched in actin and vimentin. The distribution of mRNAs for c-myc,
      glucose transporter 1, ribosomal proteins L4 and S6 and cyclin A were
      investigated by Northern hybridization of total RNA extracted from polysomes
      isolated from cytosolic, cytoskeleton and membrane fractions. The membrane-bound
      polysomes were enriched in the glucose transporter 1 mRNA and the cytoskeleton
      bound polysomes were enriched in the mRNAs for the two ribosomal proteins, c-myc
      and cyclin A. The results suggest that the mRNAs for nuclear proteins are one
      class of mRNAs which are translated on polysomes associated with the
      cytoskeleton; this may be related to the requirement to transport the newly
      synthesized protein to the nucleus.

PMID- 7646445
TI  - Role of hepatic carbonic anhydrase in de novo lipogenesis.
AB  - The role of carbonic anhydrase in de novo lipid synthesis was examined by
      measuring [1-14C]acetate incorporation into total lipids, fatty acids and non
      saponifiable lipids in freshly isolated rat hepatocytes. Two carbonic anhydrase
      inhibitors, trifluoromethylsulphonamide (TFMS) and ethoxozolamide (ETZ) decreased
      incorporation of 14C into total lipids. Both fatty acid and non-saponifiable
      lipid components of the total lipid were inhibited to approximately the same
      extent by 100 microM TFMS (29 +/- 0.3% and 35 +/- 0.3% of control respectively in
      replicate studies). However, neither drug significantly affected ATP
      concentrations or the transport activity of Na+/K(+)-ATPase, two measures of cell
      viability. To establish the site of this inhibition, water-soluble 14C-labelled
      metabolites from perchloric acid extracts of the radiolabelled cells were
      separated by ion-exchange chromatography. TFMS inhibited 14C incorporation into
      citrate, malate, alpha-oxoglutarate and fumarate, but had no effect on
      incorporation of 14C into acetoacetate. Since ATP citrate-lyase, the cytosolic
      enzyme that catalyses the conversion of citrate into acetyl-CoA, catalyses an
      early rate-limiting step in fatty acid synthesis, levels of cytosolic citrate may
      be rate controlling for de novo fatty acid and sterol synthesis. Indeed citrate
      concentrations were significantly reduced to 37 +/- 6% of control in hepatocytes
      incubated with 100 microM TFMS for 30 min. TFMS also inhibited the incorporation
      of 14C from [1-14C]pyruvate into malate, citrate and glutamate, but not into
      lactate. This supports the hypothesis that TFMS inhibits pyruvate carboxylation,
      i.e. since all of the 14C from [1-14C]pyruvate converted into citric acid cycle
      intermediates must come via pyruvate carboxylase (i.e. rather than pyruvate
      dehydrogenase). Our findings indicate a role for carbonic anhydrase in hepatic de
      novo lipogenesis at the level of pyruvate carboxylation.

PMID- 7646447
TI  - The stimulation of insulin secretion by D-glyceraldehyde correlates with its rate
      of oxidation in islet cells.
AB  - D-Glyceraldehyde's capacity to mimic the effect of D-glucose on insulin secretion
      has not yet been sufficiently substantiated. It has been recently proposed,
      however, that they might act through different mechanisms in insulin-secreting
      tumoral cells. Therefore, we have performed a dose-related study of both the
      secretory and metabolic effects of D-glyceraldehyde on islets, which have been
      compared with those produced by D-glucose. D-Glyceraldehyde's capacity to
      stimulate secretion was paralleled in a dose-dependent manner by its rate of
      oxidation to 14CO2. Partial inhibition of D-glyceraldehyde oxidation by beta
      iodoacetamide resulted in a proportional decrease in the secretory response. L
      Glyceraldehyde, which was apparently very poorly oxidized by islets, did not
      stimulate secretion. The ratio of the maximum insulin responses D-glyceraldehyde
      and D-glucose (57%) correlated with the ratio of their respective maximum rates
      of oxidation (68%). At sub-maximal concentrations there was a potentiation of the
      secretagogue effects of the hexose by the triose, which was not apparent at a
      maximum effective dose of glucose. It is concluded that D-glyceraldehyde mimics
      the secretory effect of glucose because, similarly to the hexose, it is
      metabolized through islet aerobic glycolysis. The lower potency of D
      glyceraldehyde as an insulin secretagogue than D-glucose is determined by the
      lower capacity of islets to oxidize the triose compared with the hexose. D
      Glyceraldehyde, unlike D-glucose, is metabolized in islets to D-lactate.
      Alternative routes for the metabolism of D-glyceraldehyde might explain some of
      the secretagogue differences between the triose and the hexose.

PMID- 7646446
TI  - Agonist-induced internalization and recycling of the glucagon-like peptide-1
      receptor in transfected fibroblasts and in insulinomas.
AB  - Glucagon-like peptide-1 (GLP-1) is the most potent stimulator of glucose-induced
      insulin secretion and its pancreatic beta-cell receptor is a member of a new
      subfamily of G-protein-coupled receptors which includes the receptors for
      vasoactive intestinal polypeptide, secretin and glucagon. Here we studied agonist
      induced GLP-1 receptor internalization in receptor-transfected Chinese hamster
      lung fibroblasts using three different approaches. First, iodinated GLP-1 bound
      at 4 degrees C to transfected cells was internalized with a t 1/2 of 2-3 min
      following warming up of the cells to 37 degrees C. Secondly, exposure to GLP-1
      induced a shift in the distribution of the receptors from plasma membrane
      enriched to endosomes-enriched membrane fractions, as assessed by Western blot
      detection of the receptors using specific antibodies. Thirdly, continuous
      exposure of GLP-1 receptor-expressing cells to iodinated GLP-1 led to a linear
      accumulation of peptide degradation products in the medium following a lag time
      of 20-30 min, indicating a continuous cycling of the receptor between the plasma
      membrane and endosomal compartments. Potassium depletion and hypertonicity
      inhibited transferrin endocytosis, a process known to occur via coated pit
      formation, as well as GLP-1 receptor endocytosis. In contrast to GLP-1, the
      antagonist exendin-(9-39) did not lead to receptor endocytosis. Surface re
      expression following one round of GLP-1 receptor endocytosis occurred with a half
      time of about 15 min. The difference in internalization and surface re-expression
      rates led to a progressive redistribution of the receptor in intracellular
      compartments upon continuous exposure to GLP-1. Finally, endogenous GLP-1
      receptors expressed by insulinoma cells were also found to be internalized upon
      agonist binding. Together our data demonstrate that the GLP-1 receptor is
      internalized upon agonist binding by a route similar to that taken by single
      transmembrane segment receptors. The characterization of the pathway and kinetics
      of GLP-1-induced receptor endocytosis will be helpful towards understanding the
      role of internalization and recycling in the control of signal transduction by
      this receptor.

PMID- 7646448
TI  - Histone II-A stimulates glucose-6-phosphatase and reveals mannose-6-phosphatase
      activities without permeabilization of liver microsomes.
AB  - The effect of histone II-A on glucose-6-phosphatase and mannose-6-phosphatase
      activities was investigated in relation to microsomal membrane permeability. It
      was found that glucose-6-phosphatase activity in histone II-A-pretreated liver
      microsomes was stimulated to the same extent as in detergent-permeabilized
      microsomes, and that the substrate specificity of the enzyme for glucose 6
      phosphate was lost in histone II-A-pretreated microsomes, as [U-14C]glucose-6
      phosphate hydrolysis was inhibited by mannose 6-phosphate and [U-14C]mannose 6
      phosphate hydrolysis was increased. The accumulation of [U-14C]glucose from [U
      14C]glucose 6-phosphate into untreated microsomes was completely abolished in
      detergent-treated vesicles, but was increased in histone II-A-treated microsomes,
      accounting for the increased glucose-6-phosphatase activity, and demonstrating
      that the microsomal membrane was still intact. The stimulation of glucose-6
      phosphatase and mannose-6-phosphatase activities by histone II-A was found to be
      reversed by EGTA. It is concluded that the effects of histone II-A on glucose-6
      phosphatase and mannose-6-phosphatase are not caused by the permeabilization of
      the microsomal membrane. The measurement of mannose-6-phosphatase latency to
      evaluate the intactness of the vesicles is therefore inappropriate.

PMID- 7646449
TI  - High constitutive levels of heat-shock proteins in human-pathogenic parasites of
      the genus Leishmania.
AB  - We have analysed the transcription of three heat-shock genes, HSP70, HSP83 and
      ClpB, in the protozoan parasite Leishmania. All three heat-shock genes are
      transcribed constitutively and not heat-inducibly. However, we find that two
      major heat-shock proteins, HSP70 and HSP83, are synthesized at elevated rates
      during heat stress. We conclude that the cellular stress response in Leishmaniae
      is regulated exclusively on a post-transcriptional level much in contrast with
      all other eukaryotes examined so far. The induced synthesis of HSP70 and HSP83,
      however, does not increase the steady-state level of either protein
      significantly. This is compensated by high constitutive levels of both proteins:
      HSP70 and HSP83 make up 2.1% and 2.8%, respectively, of the total protein in
      unstressed Leishmania promastigotes. Also, HSP70 is a strictly cytoplasmic
      protein in Leishmania and does not relocate into the nucleus during heat stress,
      as it does in other eukaryotes examined in the past.

PMID- 7646450
TI  - A study of novel lectins and their involvement in the activation of the
      prophenoloxidase system in Blaberus discoidalis.
AB  - Endogenous and exogenous lectins have been found to activate the prophenoloxidase
      (proPO) system of the cockroach, Blaberus discoidalis, to the same extent as
      laminarin, a previously known microbial activator of proPO. The lectins can also
      further enhance this laminarin activation of the proPO system. Non-lectin
      proteins did not display any activation properties. The time course of proPO
      activation was studied after reconstitution of the reaction system using purified
      lectins, a trypsin-like enzyme, a trypsin inhibitor and partially purified lectin
      binding proteins from the cockroach haemolymph. Lectin activation of the proPO
      system is probably not mediated by the lectin sugar-binding sites, as specific
      inhibitory sugars failed to abrogate the enhanced effect. The results suggest
      that alternative binding site(s) on the lectins may be involved in the proPO
      activation process. Evidence also suggests that several different lectins are
      involved in the regulation of the proPO system through separate receptors or
      binding molecules on the haemocytes, and that they exert their effects early in
      the sequence of events leading to conversion of proPO into its active form,
      possibly via regulation of serine proteases and protease inhibitors.

PMID- 7646451
TI  - 1 alpha,24(S)-dihydroxyvitamin D2: a biologically active product of 1 alpha
      hydroxyvitamin D2 made in the human hepatoma, Hep3B.
AB  - A major metabolite of the vitamin D analogue 1 alpha-hydroxyvitamin D2 in human
      liver cells in culture has been identified as 1 alpha,24(S)-dihydroxyvitamin D2
      [1 alpha,24(S)-(OH)2D2]. 1 alpha-Hydroxyvitamin D3 incubated with the same cells
      gives rise to predominantly 25- and 27-hydroxylated products. Our identification
      of 1 alpha,24(S)-dihydroxyvitamin D2 is based on comparisons of the liver cell
      metabolite with chemically synthesized 1 alpha,24(S)-(OH)2D2 and 1 alpha,24(R)
      (OH)2D2 by using HPLC, GC and GC-MS techniques. The stereochemical orientation of
      the 24-hydroxyl group was inferred after X-ray-crystallographic analysis of the
      24(R)-OH epimer. 1 alpha,24(S)-Dihydroxyvitamin D2 binds strongly to the vitamin
      D receptor and is biologically active in growth hormone and chloramphenicol
      acetyltransferase reporter gene expression systems in vitro, but binds poorly to
      rat vitamin D-binding globulin, DBP. We suggest that this metabolite, 1
      alpha,24(S)-(OH)2D2, possesses the spectrum of biological properties to be useful
      as a drug in the treatment of psoriasis, metabolic bone disease and cancer.

PMID- 7646452
TI  - In vivo and in vitro phosphorylation of annexin II in T cells: potential
      regulation by annexin V.
AB  - In order to understand how signal transduction occurs during T cell activation,
      it is necessary to identify the key regulatory molecules whose function is
      influenced by phosphorylation. Annexins II (A-II) and V (A-V) belong to a large
      family of Ca(2+)-dependent phospholipid-binding proteins. Among many putative
      functions, annexins may be involved in signal transduction during cellular
      proliferation and differentiation. In the present study we show that A-II is
      phosphorylated in vivo in the Jurkat human T cell line. Indeed, A-II is
      phosphorylated after stimulation by phorbol myristate acetate and on serine
      residues after T cell antigen receptor (TcR) stimulation. In cytosol from Jurkat
      cells, A-II is phosphorylated only by Ca2+/phospholipid-stimulated kinases such
      as Ca(2+)-dependent protein kinases C (cPKCs). A-V inhibits the phosphorylation
      of A-II and other substrates of cPKCs and has no effect on kinases activated only
      by phospholipids. In conclusion, A-II is phosphorylated both in vitro and in vivo
      in Jurkat cells, and may play a role as a substrate during signal transduction in
      lymphocytes via the TcR through the PKC pathway. On the other hand, A-V could act
      as a potent modulator of cPKCs in Jurkat cells.

PMID- 7646453
TI  - 3'-immature tRNA(Trp) is required for ribosome inactivation by gelonin,a plant
      RNA N-glycosidase.
AB  - Inactivation of ribosomes by gelonin, a ribosome-inactivating protein with RNA N
      glycosidase activity on 28 S rRNA, requires macromolecular cofactors present in
      post-ribosomal supernatants. One of these cofactors has been purified from a rat
      liver extract and identified as an RNA about 70 nt long which in sequence
      analysis shows a high level of similarity with mammalian (bovine) tRNA(Trp). The
      pattern of the sequencing gel is consistent with the co-existence in the
      preparation of two 3'-immature tRNA(Trp) species, missing only A75, or both A75
      and C74. In the presence of ATP, CTP and tRNA nucleotidyltransferase, the gelonin
      stimulating RNA is a good acceptor of tryptophan. An oligodeoxynucleotide
      complementary to positions 55 to 72 of mammalian (bovine) tRNA(Trp) hybridizes
      with the gelonin-stimulating RNA as demonstrated by gel mobility shift and
      ribonuclease H digestion. The oligodeoxynucleotide-directed ribonuclease H
      treatment also abolishes the gelonin-promoting activity of crude preparations of
      RNA, giving strong evidence that the only active RNA is a tRNA(Trp)-like
      molecule.

PMID- 7646454
TI  - Structural analysis of inositol phospholipids from Trypanosoma cruzi epimastigote
      forms.
AB  - Inositol phospholipids (IPL) from epimastigote forms of Trypanosoma cruzi have
      been investigated by metabolic labelling with [3H]palmitic acid and by GLC-MS
      analysis of the lipids obtained from non-labelled parasites. The IPL fraction was
      separated into phosphatidylinositol (PI) and inositol-phosphoceramide
      subfractions, the latter accounting for 80-85% of the total IPL. The neutral
      lipids released from the IPLs by PI-specific phospholipase C (PI-PLC) from
      Bacillus thuringiensis were analysed by silica-gel and reverse-phase TLC for the
      radioactive lipids and by GLC-MS for the non-radioactive samples. Ceramides
      containing dihydrosphingosine and sphingosine with C16:0 and C18:0 fatty acids
      were identified. The main component in the [3H]palmitic acid-labelled ceramides
      was palmitoyldihydrospingosine, while in the non-labelled sample the ceramides
      contained mainly sphingosine. This could reflect partial uptake of phospholipid
      from the medium. The PI contain both alkylacyl- and diacyl-glycerol lipids, with
      the ether lipid being more abundant. The latter was identified as 1-O
      hexadecylglycerol esterified by C18:2 and C18:1 fatty acids. Interestingly, the
      same lipid had been identified in the anchor of the 1G7 glycoprotein of T. cruzi
      metacyclic forms.

PMID- 7646455
TI  - Brefeldin A inhibits the endocytosis of plasma-membrane-associated heparan
      sulphate proteoglycans of cultured rat ovarian granulosa cells.
AB  - Rat ovarian granulosa cells were labelled with [35S]sulphate for 0.5-20 h and
      chased in the presence or absence of 1-2 micrograms/ml of brefeldin A (BFA) for
      up to 21 h. Heparan [35S]sulphate (HS) proteoglycans from the culture medium,
      plasma membrane and intracellular fractions were then analysed by gel
      chromatography. In the absence of BFA, about 85% of the plasma membrane
      associated HS proteoglycans were endocytosed and subsequently degraded
      intracellularly. Recirculation of the HS proteoglycans between the intracellular
      pool and the cell surface was not observed. Exposing the cells to BFA for less
      than 1 h did not influence the turnover of the HS proteoglycans, whereas the
      effect of the drug on the Golgi functions reached a maximum in approx. 10 min.
      When the cells were treated with BFA for more than 1-2 h, the rate of endocytosis
      of HS proteoglycans was reduced to about 50% of the control. The delivery of
      endocytosed HS proteoglycans to lysosomes were not affected by the drug.
      Cycloheximide also reduced the endocytosis of HS proteoglycans, but not as much
      as BFA, indicating that the inhibitory effect of BFA can be only partly accounted
      for by a block of protein transport from the endoplasmic reticulum to the plasma
      membrane. In contrast with the endocytosis of HS proteoglycans, neither that of
      125I-transferrin, known to be mediated by clathrin-coated vesicles, nor that of
      125I-ricin, a marker molecule for bulk endocytosis, was affected by BFA. The half
      life of 125I-transferrin and 125I-ricin in the plasma membrane was about 10 and
      25 min respectively compared with about 5 h for the HS proteoglycans. Altogether,
      these results indicate that the endocytosis of plasma-membrane-associated HS
      proteoglycans is mediated by different mechanisms than the endocytosis of most
      other cell-surface proteins. Further, the mechanisms involved in the endocytosis
      of HS proteoglycans are sensitive to BFA.

PMID- 7646456
TI  - The interaction of coatomer with inositol polyphosphates is conserved in
      Saccharomyces cerevisiae.
AB  - Coatomer is an oligomeric complex of coat proteins that regulates vesicular
      traffic through the Golgi complex and from the Golgi to the endoplasmic reticulum
      [Pelham (1994) Cell 79, 1125-1127]. We have investigated whether the binding of
      InsP6 to mammalian coatomer [Fleischer, Xie, Mayrleitner, Shears and Fleischer
      (1994) J. Biol. Chem. 269, 17826-17832] is conserved in the genetically amenable
      model Saccharomyces cerevisiae. We have isolated coatomer from S. cerevisiae and
      found it to bind InsP6 at two apparent classes of binding sites (KD1 = 0.8 +/-
      0.2 nM; KD2 = 361 +/- 102 nM). Ligand specificity was studied by displacing 4.5
      nM [3H]InsP6 from coatomer with various Ins derivatives. The following IC50
      values (nM) were obtained: myo-InsP6 = 6; bis(diphospho)inositol
      tetrakisphosphate = 6; diphosphoinositol pentakisphosphate = 6; scyllo-InsP6 =
      12; Ins(1,3,4,5,6)P5 = 13; Ins(1,2,4,5,6)P5 = 22; Ins(1,3,4,5)P4 = 22; 1-O-(1,2
      di-O-octanoyl-sn-glycero-3-phospho)-D-Ins(3,4,5)P3 = 290. Less than 10% of the 3H
      label was displaced by 1 microM of either Ins(1,4,5)P3 or inositol hexakis
      sulphate. A cell-free lysate of S. cerevisiae synthesized diphosphoinositol
      polyphosphates (PP-InsPn) from InsP6, but our binding data, plus measurements of
      the relative levels of inositol polyphosphates in intact yeast [Hawkins, Stephens
      and Piggott (1993) J. Biol. Chem. 268, 3374-3383], indicate that InsP6 is the
      major physiologically relevant ligand. Thus a reconstituted vesicle trafficking
      system using coatomer and other functionally related components isolated from
      yeast should be a useful model for elucidating the functional significance of the
      binding of InsP6 by coatomer.

PMID- 7646458
TI  - Comparison of the signalling properties of the long and short isoforms of the rat
      thyrotropin-releasing-hormone receptor following expression in rat 1 fibroblasts.
AB  - cDNA species encoding either the long or the short isoforms of the rat
      thyrotropin-releasing-hormone (TRH) receptor were expressed stably in Rat 1
      fibroblasts, and clones expressing specific binding of [3H]TRH were detected and
      expanded. Clones expressing each of these receptors at levels up to 1 pmol/mg of
      membrane protein were selected for analysis. Reverse-transcriptase PCR on RNA
      isolated from these clones confirmed that each clone expressed only mRNA
      corresponding to the expected splice variant. Both receptor splice variants bound
      [3H]TRH with a Kd of some 80 nM when binding assays were performed in the
      presence of guanosine 5'-[beta gamma-imido]-triphosphate. In the presence of TRH,
      both receptor subtypes were able to cause stimulation of inositol phosphate
      generation in a pertussis-toxin-insensitive manner with similar EC50 values and
      to stimulate the mobilization of intracellular Ca2+, but, despite reports that
      TRH receptors can also interact with the G-proteins Gs and Gi2, neither receptor
      splice variant was able to modulate adenylate cyclase activity in either a
      positive or a negative manner. These data indicate that the long and short
      isoforms of the rat TRH receptor have similar affinities for TRH and display
      similar abilities to interact with the Gq-like G-proteins, but show no ability to
      regulate adenylate cyclase, at least when expressed in this genetic background.

PMID- 7646457
TI  - Diphtheria toxin endocytosis and membrane translocation are dependent on the
      intact membrane-anchored receptor (HB-EGF precursor): studies on the cell
      associated receptor cleaved by a metalloprotease in phorbol-ester-treated cells.
AB  - Preincubation of Vero cells with 1 microM phorbol 12-myristate 13-acetate (PMA)
      decreased the specific binding of diphtheria toxin by about 50%, whereas the
      toxic effect, endocytic uptake and membrane translocation were completely
      blocked. Toxin bound to PMA-treated cells was released upon incubation with
      heparinase. The effect of PMA was abrogated in the presence of EDTA or N-(DL-[2
      (hydroxyaminocarbonyl)methyl]-4-methyl-pentanoyl)-L-3-(2' - naphthyl)-alanyl-L
      alanine 2-aminoethyl-amide (TAPI), a specific inhibitor of matrix
      metalloproteases. The results indicate that PMA induces proteolytic cleavage of
      the diphtheria-toxin receptor [heparin-binding EGF-like growth factor (HB-EGF)
      precursor] outside the membrane anchor, and that about 50% of the growth-factor
      ecto-domain remains associated with the cells, due to binding to surface
      proteoglycans containing heparan sulphates. Although the cleaved cell-associated
      HB-EGF binds diphtheria toxin, it does not serve as a functional receptor, since
      neither toxin internalization nor translocation occurs. Thus the intact HB-EGF
      precursor is of crucial importance for its function as the diphtheria-toxin
      receptor.

PMID- 7646459
TI  - Long-term reduction of amplified ornithine decarboxylase sequences in human
      myeloma cells.
AB  - (1) Human myeloma cell line Sultan, resistant to 20 mM difluoro-methylornithine
      (DFMO) owing to ornithine decarboxylase (ODC) gene amplification, was grown in
      the absence of DFMO for a period of 10 months. The gene copy number and
      methylation status of the ODC gene were monitored after withdrawal of DFMO.
      Moreover, levels of ODC mRNA, immunoreactive ODC protein, ODC activity and
      polyamine levels were recorded recurrently during the course of the study. (2)
      The results revealed that ODC gene copy number started to decrease after 4 weeks
      growth without DFMO, to a final level of less than 30% of the original gene
      dosage. The methylation status of the ODC gene, however, remained almost
      unaltered, displaying only a modest increase in methylation after 10 months
      without DFMO. The amount of ODC message dropped very rapidly to 75% of the
      original value, then started to decrease in a gene copy-number-dependent manner.
      The amount of ODC protein closely followed the levels of mRNA during the study,
      whereas the ODC activity, after a transient increase during the first week,
      decreased to half of the original level after 4 weeks. Between 6 and 16 weeks ODC
      activity stabilized to a fifth of the original value and no more changes were
      detected during the subsequent period of observation. (3) Due to the grossly
      elevated ODC enzyme activity, levels of putrescine and spermidine first peaked
      and then stabilized at 6 weeks after DFMO withdrawal. The final spermidine level
      was comparable with that of the parental Sultan cell line with only one copy of
      active ODC gene. However, putrescine content was strikingly elevated, being
      stabilized to a level that was 20 times higher than in parental cells. Spermine
      concentration was practically unchanged during the study. (4) According to the
      results obtained in this study, the abnormal level of ODC expression in human
      myeloma cells is suppressed partially at the level of transcription or post
      transcriptionally, but it is not due to increased methylation of the gene. The
      major regulatory mechanism to compensate for a highly elevated ODC expression was
      modulation of the enzyme activity. After 10 months without DFMO, the cells still
      displayed about 20 times higher ODC activity and putrescine concentration than
      the myeloma cell line with a single copy of the ODC gene. They did not, however,
      show any signs of growth retardation or other features different from the
      parental cells.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7646460
TI  - Lovastatin enhances the photocytotoxicity of UVA radiation towards cultured
      N.C.T.C. 2544 human keratinocytes: prevention by cholesterol supplementation and
      by a cathepsin inhibitor.
AB  - The effect of the hydroxymethylglutaryl-CoA (HMG-CoA) inhibitor lovastatin on the
      UVA-induced photocytotoxicity has been investigated in cultured human N.C.T.C.
      2544 keratinocytes. In the absence of irradiation, 5 x 10(-7) M lovastatin did
      not exhibit any significant cytotoxic effect towards this cell line. Although the
      drug cannot act as a photosensitizer, because it does not absorb in the UVA
      range, it markedly increased the UVA-induced cellular damage (about 70% reduction
      in cell viability at 5 x 10(-7) M). This effect was not accompanied by an
      increase in the lipid peroxidation product content of cells as compared with
      treatment with UVA alone. Medium supplementation with 0.01 mg/ml free cholesterol
      totally prevented the enhancement of UVA photocytotoxicity induced by lovastatin.
      A protective effect was also observed when cells were supplemented with an amount
      of low-density lipoprotein giving the same cholesterol concentration in the
      culture medium. Finally, E64 [L-trans-epoxysuccinyl-leucylamido-(4-guanidino)
      butane], a lysosomal cathepsin inhibitor, also prevents the cell death induced by
      UVA in cells treated with lovastatin. These results suggest that HMG-CoA
      reductase inhibitors could increase the sensitivity of skin cells to UVA
      radiation, and that this phenomenon is related to lysosomal enzyme release.

PMID- 7646461
TI  - Identification of periplasmic nitrate reductase Mo(V) EPR signals in intact cells
      of Paracoccus denitrificans.
AB  - EPR spectroscopy has been successfully used to detect signals due to molybdenum
      (V) and ferric iron in intact cells of aerobically grown Paracoccus
      denitrificans. The signals are ascribed to the catalytic molybdenum centre and to
      the haem iron of the periplasmic nitrate reductase. These signals are absent from
      a mutant strain deficient in this enzyme. The Mo(V) signal is due to the High-g
      Split species which has been well characterized in the purified enzyme. This
      confirms that the High-g Split is the physiologically relevant signal of a number
      observed in the previous work on the purified enzyme.

PMID- 7646462
TI  - Characterization of binding of human beta 2-glycoprotein I to cardiolipin.
AB  - beta 2-Glycoprotein I-cardiolipin complexes are reported to be a target antigen
      for the binding of a subset of anti-phospholipid antibodies. The characteristics
      of binding of beta 2-glycoprotein I to cardiolipin are reported in this paper.
      Binding at neutral pH is specific, saturable, dependent on ionic strength and
      independent of bivalent cation. Binding at low pH is qualitatively different from
      that at neutral pH, and is not dependent on ionic strength. Denaturation of beta
      2-glycoprotein I by heat inactivation and reduction/alkylation indicates that
      beta 2-glycoprotein I-cardiolipin interaction does not require the native three
      dimensional structure of beta 2-glycoprotein I, implying that a linear sequence
      motif may be responsible. Modification of amino acid residues by KCNO treatment
      completely destroys binding capacity, indicating crucial involvement of lysine
      residues in binding of beta 2-glycoprotein I to cardiolipin. Complement factor H,
      which has some similar highly charged linear sequence motifs to beta 2
      glycoprotein I and is composed of the same type of protein module, was found to
      bind to cardiolipin and inhibit the binding of beta 2-glycoprotein I to
      cardiolipin. Three different lysine-rich segments of the fifth domain of beta 2
      glycoprotein I may be involved in binding to cardiolipin.

PMID- 7646463
TI  - Elimination of glycosylation heterogeneity affecting heparin affinity of
      recombinant human antithrombin III by expression of a beta-like variant in
      baculovirus-infected insect cells.
AB  - In order to promote homogeneity of recombinant antithrombin III interactions with
      heparin, an asparagine-135 to alanine substitution mutant was expressed in
      baculovirus-infected insect cells. The N135A variant does not bear an N-linked
      oligosaccharide on residue 135 and is therefore similar to the beta isoform of
      plasma antithrombin. Purified bv.hat3.N135A is homogeneous with respect to
      molecular mass, charge and elution from immobilized heparin. Second-order rate
      constants for thrombin and factor Xa inhibition determined in the absence and
      presence of heparin are in good agreement with values established for plasma
      antithrombin and these enzymes. Based on far- and near-UV CD, bv.hat3.N135A has a
      high degree of conformational similarity to plasma antithrombin. Near-UV CD,
      absorption difference and fluorescence spectroscopy studies indicate that it also
      undergoes an identical or very similar conformational change upon heparin
      binding. The Kds of bv.hat3.N135A for high-affinity heparin and pentasaccharide
      were determined and are in good agreement with those of the plasma beta
      antithrombin isoform. The demonstrated similarity of bv.hat3.N135A and plasma
      antithrombin interactions with target proteinases and heparins suggest that it
      will be a useful base molecule for investigating the structural basis of
      antithrombin III heparin cofactor activity.

PMID- 7646464
TI  - An inverted TATA box directs downstream transcription of the bone sialoprotein
      gene.
AB  - The orientation of the TATA box is thought to direct downstream transcription of
      eukaryotic genes by RNA polymerase II. However, the putative TATA box in the
      promoter of the bone sialoprotein (BSP) gene, which codes for a tissue-specific
      and developmentally regulated bone matrix protein, is inverted (5'-TTTATA-3')
      relative to the consensus TATA box sequence (5'-TATAAA-3') and is overlapped by a
      vitamin D3-response element. Here we show that the inverted TATA sequence in the
      rat BSP gene binds to recombinant TATA-box-binding protein (TBP) with an affinity
      similar to that observed with the consensus TATA box, and site-directed point
      mutations in the inverted TATA sequence (mutating TTTATA into TCTCTA) abrogate
      both TBP binding and BSP promoter activity. However, when the inverted TATA
      sequence is changed to a canonical TATAAA, the TBP- and vitamin D3 receptor
      binding properties together with the BSP promoter activity are retained. In
      addition, we found that the TBP is required to reconstitute in vitro
      transcription driven by the BSP promoter. These studies, which have revealed a
      naturally occurring inverted TATA box that can bind TBP and direct downstream
      transcription, demonstrate that the orientation of the TATA box does not
      determine the direction of transcription in higher eukaryotic genes.
      Consequently, the inverted TATA box that is conserved in the human, rat and mouse
      BSP gene promoters will provide an excellent in vivo model to investigate the
      polarity of the transcription factor IID-DNA complex and its relation to
      downstream transcription.

PMID- 7646465
TI  - Large variations in the proteolytic formation of a chromogranin A-derived peptide
      (GE-25) in neuroendocrine tissues.
AB  - We have established a radioimmunoassay for GE-25, a peptide present in the C
      terminal end of the primary amino acid sequence of chromogranin A where it is
      flanked by typical proteolytic cleavage sites. Gel-filtration HPLC was used to
      characterize the molecular sizes of the immunoreactive molecules. The antiserum
      recognized not only the free peptide but also larger precursors including the
      proprotein chromogranin A. The tissues with the highest levels of GE-25
      immunoreactivity were in decreasing order: the adrenal medulla, the three lobes
      of the pituitary gland, intestinal mucosa, pancreas and various brain regions. In
      adrenal medulla and parathyroid gland most of the immunoreactivity was found to
      be present as intact chromogranin A and some intermediate-sized peptides, without
      significant amounts of the free peptide. In anterior pituitary, and even more so
      in intestine, a shift to smaller peptides was seen. In the posterior and
      intermediate pituitary and in pancreas the predominant immunoreactive material
      was apparently represented by the free peptide GE-25. In reverse-phase
      chromatography this peptide eluted exactly like the synthetic standard, which
      allows a tentative identification as GE-25. In brain tissue the processing of
      chromogranin A was intermediate, with significant amounts of immunoreactivity
      corresponding to GE-25 as well as precursor proteins being present. We suggest
      that in those organs (endocrine pancreas, intermediate and posterior pituitary)
      where the major hormones are proteolytically processed there is also a
      concomitant proteolysis of further susceptible peptides. Since GE-25 is
      apparently formed in vivo and is well conserved between species it seems a good
      candidate for having specific physiological functions.

PMID- 7646466
TI  - Transcriptional and post-transcriptional regulation of the receptor for urokinase
      type plasminogen activator by cytokines and tumour promoters in the human lung
      carcinoma cell line A549.
AB  - The receptor for urokinase-type plasminogen activator (uPAR) is an integral
      membrane protein that specifically binds urokinase-type plasminogen activator
      (uPA) and plays a crucial role in cell surface plasmin generation. We have
      previously found that transforming growth factor-beta, type 1 (TGF-beta 1),
      increases uPAR gene transcription in the human lung carcinoma cell line A549 and
      now report that also epidermal growth factor (EGF) and the tumour promoter
      phorbol 12-myristate 13-acetate (PMA) cause increased uPAR transcription and that
      PMA and TGF-beta 1 in addition increase the stability of uPAR mRNA, while EGF has
      no effect on this parameter. All three compounds also increase the uPAR protein
      level, as measured by cell-binding experiments with radiolabelled ligand. The
      increase in uPAR protein level was however considerably lower with all three
      compounds than the increase in mRNA level, suggesting that they also exert a
      translational or post-translational control. Accompanying the increase in the
      number of uPAR molecules there was a proportional decrease in their ligand
      binding affinity, the mechanism of which is unknown. Platelet-derived growth
      factor, basic fibroblast growth factor and cyclic AMP analogues did not induce
      any change in the uPAR mRNA level in A549 cells. Previous studies have shown that
      expression of uPA and its type-1 inhibitor is regulated by a variety of cytokines
      in a cell-specific manner. The present study indicates that cytokines in addition
      influence cell surface plasminogen activation by regulating uPAR expression.

PMID- 7646467
TI  - Sequencing and expression of a cDNA for human glutathione synthetase.
AB  - A human brain cDNA clone encoding glutathione synthetase (EC 6.3.2.3) has been
      sequenced and expressed in Escherichia coli. The protein is 474 amino acids in
      length with a subunit molecular mass of 52,352 Da. The recombinant protein
      exhibits glutathione synthetase activity and occurs as a homodimer. The
      recombinant glutathione synthetase was purified to homogeneity and had a specific
      activity of 1.73 mumol/min per mg of protein, an isoelectric point of 5.35 and a
      pH optimum between 7.0 and 7.5. Southern blots of human genomic DNA hybridized
      with the glutathione synthetase cDNA revealed a relatively simple pattern of
      strongly hybridizing fragments, indicating the absence of a large gene family and
      suggesting that there may be only one glutathione synthetase gene in the human
      genome.

PMID- 7646468
TI  - Beta-migrating very-low-density lipoprotein, chylomicron remnants and their
      receptors.

PMID- 7646469
TI  - Beta-migrating very-low-density lipoproteins and chylomicron remnants bind to rat
      liver hepatocytes at a low-density-lipoprotein-receptor-independent site (the
      remnant receptor).

PMID- 7646470
TI  - Bovine gall-bladder mucin contains two distinct tandem repeating sequences:
      evidence for scavenger receptor cysteine-rich repeats.
AB  - Gall-bladder mucin is a densely glycosylated macromolecule which is the primary
      secretory product of the gall-bladder epithelium. It has been shown to bind
      cholesterol and other biliary lipids and to promote cholesterol crystal
      nucleation in vitro. In order to understand the molecular basis for mucin-lipid
      interactions, bovine gall-bladder mucin cDNAs were identified by expression
      cloning and were isolated and sequenced. The nucleotide sequences of these cDNAs
      revealed two distinct tandem repeating domains. One of these domains contained a
      20-amino acid tandem repeating sequence enriched in threonine, serine and
      proline. This sequence was similar to, but not identical with, the short tandem
      repeating sequences identified previously in other mammalian mucins. The other
      domain contained a 127-amino acid tandem repeating sequence enriched in cysteine
      and glycine. This repeat displayed considerable sequence similarity to a family
      of receptor- and ligand-binding proteins containing scavenger receptor cysteine
      rich repeats. By analogy with other proteins containing these cysteine-rich
      repeats, it is possible that, in gall-bladder mucin, this domain serves as a
      binding site for hydrophobic ligands such as bilirubin, cholesterol and other
      biliary lipids.

PMID- 7646471
TI  - Thrombin-thrombomodulin interaction: energetics and potential role of water as an
      allosteric effector.
AB  - The interaction of rabbit lung thrombomodulin (TM) and C-terminal hirudin 54-65
      fragment (Hir54-65) with human alpha-thrombin were investigated by exploiting
      their competitive inhibition of thrombin-fibrinogen interaction. Measurements of
      Ki values for TM and Hir54-65 interactions with human alpha-thrombin performed
      over a temperature range spanning from 10 to 40 degrees C showed a constant
      enthalpy for both ligands. The enthalpic and entropic contributions to the free
      energy of binding, however, are different for TM and the hirudin peptide. The
      calculated values of delta H and delta S, in fact, were -47.3 +/- 2.51 kJ (-11.3
      +/- 0.6 kcal)/mol and -42.7 +/- 7.9 J (-10.2 +/- 1.9 cal)/mol.K for the hirudin
      peptide, while being -22.9 +/- 2.09 kJ (-5.47 +/- 0.5 kcal)/mol and 102.50 +/-
      6.69 J (24.5 +/- 1.6 cal)/mol.K respectively for TM binding. These findings
      indicate that the interaction between thrombin and Hir54-65 is largely driven by
      the enthalpic contribution, whereas the positive entropy change is the driving
      force for the formation of the thrombin-TM complex. In other experiments
      performed in the presence of various concentrations of either sorbitol or sucrose
      it could be demonstrated that the value of the equilibrium association constant
      for thrombin-TM interaction increases as a function of the osmotic pressure,
      while the thrombin-Hir54-65 interaction was not affected by the same conditions.
      Moreover, control experiments showed that no major conformational changes are
      produced on TM by osmotic pressures used in the present study. From these
      experiments it was calculated that roughly 35 water molecules are released into
      the bulk water upon TM binding. Such a phenomenon, which is likely to be
      responsible for the entropic change described above, indicates the relevance of
      hydration processes for the formation of the thrombin-TM adduct.

PMID- 7646472
TI  - Kinetic investigation of the action of hyaluronidase on hyaluronan using the
      Morgan-Elson and neocuproine assays.
AB  - In this paper we describe kinetic investigations of the action of testicular
      hyaluronidase on hyaluronan. We have compared the use of two spectrophotometric
      assays, the first based on the Morgan-Elson reaction and the second on the
      neocuproine reaction. With the neocuproine reaction Km was found to be 0.46 mg/ml
      and Vmax to be 126 nmol l-1 s-1. Because of a low sensitivity and the production
      of interfering precipitates, the Morgan-Elson assay cannot be used for kinetic
      investigation of the enzyme. Furthermore this assay is prone to interference from
      compounds such as disodium cromoglycate, (+)-catechine, penicillamine, CaCl2 and
      acetate buffer.

PMID- 7646473
TI  - Modulation of glucagon-induced glucose production by dexfenfluramine in rat
      hepatocytes.
AB  - The mechanism of the antihyperglycaemic action of dexfenfluramine (DEXF) was
      investigated in isolated rat hepatocytes exposed to glucagon. Preincubation of
      hepatocytes with DEXF caused a dose-dependent inhibition of cyclic AMP formation
      by 100 nM glucagon (Ki = 0.29 mM) that was almost complete at 1 mM DEXF.
      Surprisingly, glucagon-induced phosphorylase activation was not affected by DEXF
      despite the significant drop in cyclic AMP levels. Glucose production stimulated
      by glucagon was inhibited by up to 48% by 1 mM DEXF, and the rate of glucose
      production correlated positively with the steady-state concentration of glucose 6
      phosphate. DEXF also partially restored lactate + pyruvate production which was
      abolished by an optimal concentration of glucagon. Although DEXF was not able to
      prevent the inactivation of pyruvate kinase by glucagon, the lack of further
      accumulation of phosphoenolpyruvate in DEXF-treated cells supports the conclusion
      that the flux through pyruvate kinase is stimulated, probably via the increase in
      fructose 2,6-bisphosphate, thereby increasing glycolysis. Our results thus
      indicate that DEXF counteracts the inhibition of glycolysis by glucagon and that
      this property might contribute to the antihyperglycaemic effect of this drug.
      Furthermore, this study shows that, in the presence of the drug, glucagon caused
      phosphorylase activation and pyruvate kinase inactivation without a significant
      increase in cyclic AMP levels.

PMID- 7646474
TI  - Post-transcriptional mechanisms are responsible for the reduction in lipoprotein
      lipase activity in cardiomyocytes from diabetic rat hearts.
AB  - Lipoprotein lipase (LPL) activity is reduced in cardiomyocytes from rat hearts
      following the acute (4-5 day) induction of diabetes with 100 mg/kg
      streptozotocin. The molecular basis for this inhibitory effect of diabetes on LPL
      activity was investigated by measuring steady-state LPL mRNA content and the
      synthesis and turnover of LPL protein ([35S]methionine incorporation into
      immunoprecipitable LPL protein in pulse and pulse-chase experiments) in control
      and diabetic cardiomyocytes. LPL activity was reduced to approx. 50% of control
      in diabetic cardiomyocytes, but LPL mRNA levels and turnover (degradation) of
      newly synthesized LPL were unchanged. Synthesis of total protein and LPL were
      reduced to 72% and 71% of control respectively; therefore, relative rates of LPL
      synthesis were the same in control and diabetic cardiomyocytes. The diabetes
      induced reduction in LPL synthesis was accompanied by a decrease in LPL mass to
      78% of control, and a decrease in enzyme specific activity (0.48 to 0.33 m
      unit/ng of LPL protein) since the decline in catalytic activity was greater than
      the decrease in LPL synthesis and mass. Thus, post-transcriptional mechanisms
      involving a reduction in LPL synthesis as part of a generalized decrease in total
      protein synthesis, together with a post-translational mechanism(s) that result in
      accumulation of inactive LPL protein, are responsible for the decreased LPL
      activity in cardiomyocytes from diabetic rat hearts.

PMID- 7646475
TI  - Glutamate stably enhances the activity of two cytosolic forms of phospholipase A2
      in brain cortical cultures.
AB  - The mechanisms by which glutamatergic neurotransmitters modulate neuronal lipid
      metabolism are not well established. We have directly measured phospholipase A2
      (PLA2) enzymic activity in cell-free extracts from cortical neuronal cultures
      from rat brain and have found that the PLA2 activity is up-regulated after cells
      are exposed to glutamate. Brief exposure to a calcium ionophore or phorbol 12
      myristate 13-acetate (PMA) stably enhanced PLA2 activity. Down-regulation of
      protein kinase C activity partially blocked glutamate's effects. Two Ca(2+)-and
      pH-dependent forms of PLA2 were identified in cytosolic extracts. Activation of
      both forms of PLA2 was enhanced by prior exposure of the cultures to glutamate.
      One of the two forms had chromatographic characteristics on heparin-Sepharose,
      Mono Q and Superose 12 columns similar to the 100 kDa cytosolic PLA2 (cPLA2), and
      was recognized by an antibody raised to pig spleen cPLA2. The second form was
      similar in size to Group-I and -II PLA2s but differed in chromatographic
      characteristics. It was not inhibited by dithiothreitol, and did not react with
      antibodies to pancreatic Group-I PLA2, features that distinguish it from Group-I
      and -II PLA2. In extracts from cells pretreated with glutamate, the activity-Ca2+
      concentration dose-response relationship of the 13.5 kDa form of PLA2 was shifted
      to the left with activation at lower Ca2+ concentration as the result of stable
      modification of the enzyme induced by glutamate. Thus glutamate-induced stable
      enhancement of PLA2 activity, by processes involving calcium and protein kinase C
      activation, is a potential molecular switch probably mediating changes in
      synaptic function and contributing to excitotoxicity.

PMID- 7646477
TI  - A novel protein, amyloid precursor-like protein 2, is present in human brain,
      cerebrospinal fluid and conditioned media.
AB  - A monoclonal antibody, 3B11, was raised to a novel protein, amyloid precursor
      like protein 2, which did not recognize amyloid precursor protein. Multiple bands
      were detected in human brain fractions and cell lysate by Western blotting,
      indicating the presence of isoforms, 3B11 immunoreactivity was also detected in
      cerebrospinal fluid and conditioned medium, indicating that the protein is
      secreted. Immunocytochemistry revealed 3B11 immunoreactivity in sections of human
      brain.

PMID- 7646476
TI  - Residues in the synuclein consensus motif of the alpha-synuclein fragment, NAC,
      participate in transglutaminase-catalysed cross-linking to Alzheimer-disease
      amyloid beta A4 peptide.
AB  - The widespread deposition of amyloid plaques is one of the hallmarks of Alzheimer
      disease (AD). A recently described component of amyloid plaques is the 35-residue
      peptide, non-A beta component of AD amyloid, which is derived from a larger
      intracellular neuronal constituent, alpha-synuclein. We demonstrate that
      transglutaminase catalyses the formation of the covalent non-A beta component of
      AD amyloid polymers in vitro as well as polymers with beta-amyloid peptide, the
      major constituent of AD plaques. The transglutaminase-reactive amino acid
      residues in the non-A beta component of AD amyloid were identified as Gln79 and
      Lys80. Lys80 is localized in a consensus motif Lys-Thr-Lys-Glu-Gly-Val, which is
      conserved in the synuclein gene family. Thus transglutaminase might be involved
      in the formation of insoluble amyloid deposits and participate in the
      modification of other members of the synuclein family.

PMID- 7646478
TI  - Fractious chromosomes: hybrid disruption and the origin of selfish genetic
      elements.
AB  - Supernumerary B chromosomes are dispensable elements of the genome which can be
      retained in populations at high frequencies, despite being deleterious, through
      the ability to undergo non-Mendelian inheritance. Their mode of origin is,
      however, obscure. Recent work on gynogenetic fish has demonstrated the
      incorporation of small, unstable, centromere-containing microchromosomes,
      probably of interspecific derivation, into an asexual lineage (1). That these
      resemble B chromosomes both in structure and behaviour is consistent with the
      proposal that hybridisation between closely related species may be a significant
      mode of origin for such selfish genetic elements. Additional work on the B
      chromosome of a parasitoid wasp and observations on patterns of chromosome
      breakage from somatic cell hybrids also support this hypothesis.

PMID- 7646479
TI  - Are competing intermolecular and intramolecular interactions of PERIOD protein
      important for the regulation of circadian rhythms in Drosophila?
AB  - Genetic analysis is revealing molecular components of circadian rhythms. The gene
      products of the period gene in Drosophila and the frequency gene in Neurospora
      oscillate with a circadian rhythm. A recent paper (1) has shown that the PERIOD
      protein can undergo both intermolecular and intramolecular interactions in vitro.
      The effects of temperature and two period mutations on these molecular
      interactions were compared to the effects of the mutations and temperature on the
      in vivo period length of circadian rhythms. The results suggest that the
      molecular interactions may compete to maintain a rhythm with a constant period
      over a wide temperature range.

PMID- 7646480
TI  - Nuclear organization: uniting replication foci, chromatin domains and chromosome
      structure.
AB  - In higher eukaryotes, 'replication factories' coordinate DNA synthesis within
      local clusters of chromatin domains. Recent experiments (1, 2) have confirmed the
      complexity of these clusters and established that the organization of sites
      labelled during S phase persists throughout the cell cycle. This implies that
      domain clusters are critical elements of an hierarchy that is fundamental to both
      nuclear and chromosome structure.

PMID- 7646481
TI  - Steps towards a mouse model of Alzheimer's disease.
AB  - Alzheimer's disease, a form of senile dementia, is characterised by two kinds of
      pathological deposits in the brain, called plaques and tangles. The molecular
      nature of the deposits has been identified but there is as yet little
      understanding of the underlying biochemistry and cell biology that lead to their
      formation. Progress in this area would be greatly aided by a realistic animal
      model. Two recent papers describe the production of transgenic mice that develop
      significant aspects of the Alzheimer-like pathology. The mice produced by Games
      et al.(1) develop plaques while those produced by Gotz et al.(2) display the
      early stages of tangle pathology.

PMID- 7646482
TI  - The significances of bacterial colony patterns.
AB  - Bacteria do many things as organized populations. We have recently learned much
      about the molecular basis of intercellular communication among prokaryotes.
      Colonies display bacterial capacities for multicellular coordination which can be
      useful in nature where bacteria predominantly grow as films, chains, mats and
      colonies. E. coli colonies are organized into differentiated non-clonal
      populations and undergo complex morphogenesis. Multicellularity regulates many
      aspects of bacterial physiology, including DNA rearrangement systems. In some
      bacterial species, colony development involves swarming (active migration of cell
      groups). Swarm colony development displays precise geometrical controls and
      periodic phenomena. Motile E. coli cells in semi-solid media form organized
      patterns due to chemotactic autoaggregation. On poor media, B. subtilis forms
      branched colonies using group motility and long-range chemical signalling. The
      significances of bacterial colony patterns thus reside in a deeper understanding
      of prokaryotic biology and evolution and in experimental systems for studying
      self-organization and morphogenesis.

PMID- 7646483
TI  - In vivo biochemistry: physical monitoring of recombination induced by site
      specific endonucleases.
AB  - The recombinational repair of chromosomal double-strand breaks (DSBs) is of
      critical importance to all organisms, who devote considerable genetic resources
      to ensuring such repair is accomplished. In Saccharomyces cerevisiae, DSB
      mediated recombination can be initiated synchronously by the conditional
      expression of two site-specific endonucleases, HO or I-Scel. DNA undergoing
      recombination can then be extracted at intervals and analyzed. Recombination
      initiated by meiotic-specific DSBs can be followed in a similar fashion. This
      type of 'in vivo biochemistry' has been used to describe several discrete steps
      in two different homologous recombination pathways: gene conversion and single
      strand annealing. The roles of specific proteins during recombination can be
      established by examining DNA in strains deleted for the corresponding gene. These
      same approaches are now becoming available for the study of recombination in both
      higher plants and animals. Physical monitoring can also be used to analyze
      nonhomologous recombination events, whose mechanisms appear to be conserved from
      yeast to mammals.

PMID- 7646484
TI  - Modulation of AP-1/ATF transcription factor activity by the adenovirus-E1A
      oncogene products.
AB  - The proteins encoded by early region 1 A (E1A) of human adenoviruses (Ad)
      modulate the expression of both adenovirus genes and various host cell genes.
      With these transcription-regulating properties the E1A proteins redirect the
      cell's metabolism, which enables them to induce oncogenic transformation in
      rodent cells. The E1A proteins modulate transcription by interacting both with
      gene-specific and general cellular transcription factors. Various members of the
      AP-1 and ATF/CREB families of transcription factors are targets for E1A-dependent
      regulation, including cJun, the protein product of the c-jun proto-oncogene. The
      E1A proteins modulate cJun-dependent transcription both positively and
      negatively, and affect the activity as well as the expression levels of cJun. By
      increasing the phosphorylation status of cJun, E1A can stimulate transcription
      regulated by cJun/ATF2 heterodimers. In contrast, E1A inhibits the expression of
      various metalloproteases by interfering with the DNA-binding capacity of
      cJun/cJun and cJun/cFos dimers, which might involve the association of E1A with
      the putative transcriptional coactivator p300. Since the ability of E1A to alter
      cJun-dependent transcription correlates with its transforming capacity,
      interference with cJun-dependent transcription may be an essential step in E1A
      induced transformation.

PMID- 7646485
TI  - bcl-2, a novel regulator of cell death.
AB  - The bcl-2 gene product, a 25 kDa membrane protein residing at mitochondrial,
      microsomal and nuclear membrane sites within many cell types, is a broad and
      potent inhibitor of cell death by apoptosis. A family of bcl-2-related genes with
      death-inhibiting or -promoting actvities has recently been described, indicating
      a potentially quite complex cell death regulatory network at the level of gene
      expression and protein-protein interactions. The function of bcl-2 may be to
      regulate a final common pathway in apoptosis. Current hypotheses suggest that
      oxidative stress, specific proteolytic activity or cell cycle control may be
      common elements in apoptosis through which bcl-2 exerts its survival function.
      Based on the extent to which elements of apoptotic pathways overlap with non
      apoptotic cellular functions, the physiological role of bcl-2 may also extend to
      other cellular processes such as differentiation and proliferation.

PMID- 7646486
TI  - A 200-amino acid ATPase module in search of a basic function.
AB  - A fast growing family of ATPases has recently been highlighted. It was named the
      AAA family, for ATPases Associated to a variety of cellular Activities. The key
      feature of the family is a highly conserved module of 230 amino acids present in
      one or two copies in each protein. Despite extensive sequence conservation, the
      members of the family fulfil a large diversity of cellular functions: cell cycle
      regulation, gene expression in yeast and HIV, vesicle-mediated transport,
      peroxisome assembly, 26S protease function etc. In addition, several members of
      this family can be found in the same organism (up to 17 in S. cerevisiae). The
      contrast between functional diversity and structural conservation of the module,
      from archaebacteria to mammals, suggests that it plays an essential, but as yet
      unknown, role at key points of the cellular machinery. Two (non-exclusive) such
      possibilities are: (1) ATP-dependent proteasome function and (2) ATP-dependent
      anchorage of proteins. Finally, the basic biochemical activity of the AAA module
      is still a matter of speculation, and we propose that it acts as an ATP-dependent
      protein clamp.

PMID- 7646487
TI  - UV-induced skin cancer in a hairless mouse model.
AB  - Ultraviolet (UV) radiation is a very common carcinogen in our environment, but
      epidemiological data on the relationship between skin cancers and ambient solar
      UV radiation are very restricted. In hairless mice the process of UV
      carcinogenesis can be studied in depth. Experiments with this animal model have
      yielded quantitative data on how tumor development depends on dose, time and
      wavelength of the UV radiation. In combination with epidemiological data, these
      experimental results can be transposed to humans. Comparative studies on
      molecular, cellular and physiological changes in mouse and man can further our
      fundamental understanding of UV carcinogenesis in man. This is likely to improve
      risk assessments such as those related to stratospheric ozone depletion, and to
      yield well-targeted intervention schemes, e.g. prescribing a specific drug or
      diet, for high-risk individuals.

PMID- 7646488
TI  - Rapid detection of selected aneuploidies by quantitative fluorescent PCR.
AB  - Selected aneuploidies can be rapidly diagnosed by the analysis of fluorescent
      polymerase chain reaction (PCR) products of chromosome-specific and highly
      polymorphic small tandem repeats (STRs). The quantitative STR patterns obtained
      from samples of normal individuals are markedly different from those seen when
      patients with aneuploidies involving chromosome X, or trisomies of chromosomes 21
      and 18, are tested. For example, while samples from normal subjects--tested with
      a chromosome 21-derived STR (D21S11)--show two fluorescent PCR peaks with similar
      activities in a 1:1 ratio, the analysis of samples from patients with trisomy 21
      reveals the presence of either three peaks (ratio 1:1:1), or two peaks with a
      ratio of 2:1. The use of an internal non-polymorphic marker allows identification
      of trisomic samples with three copies of the same allele. This rapid approach (24
      hours) is particularly valuable when applied to prenatal diagnosis of chromosomal
      abnormalities since it reduces the time of anxiety of the parents waiting for the
      results of the conventional cytogenetic tests, which require several weeks.

PMID- 7646489
TI  - A preadipocyte clonal line from bovine intramuscular adipose tissue:
      nonexpression of GLUT-4 protein during adipocyte differentiation.
AB  - A clonal bovine intramuscular preadipocyte (BIP) line has been established from
      the intramuscular white adipose tissue of the M. longissimus thoracis in each of
      three Japanese Black cattle. Exponentially growing BIP cells exhibited a
      fibroblastic appearance. Adipocyte differentiation was initiated by treating
      confluent BIP cells with differentiation medium containing insulin and
      dexamethasone. Small lipid droplets appeared 5-6 days after stimulation and
      occupied a large fraction of the cell volume at 10 days and beyond. During the
      adipose conversion, the incorporation of acetate to the cells gradually increased
      by 10-fold and reached a maximum at day 5. However, incorporation of glucose
      increased only 3-folds prior to this conversion, even though GLUT-1 level
      increased by 13-fold at day 7. GLUT-4, on the other hand, was not detected during
      the course of differentiation. These results suggested that adipose tissue
      metabolisms in ruminants were different from that of non-ruminants.

PMID- 7646490
TI  - Effect of gamma-aminobutyric acid on the carnitine metabolism in neural cells.
AB  - Isolated rat cerebral cortex cells were able to accumulate L-carnitine and this
      process was competitively inhibited by 1 mM gamma-aminobutyric acid (GABA) with a
      shift of Km from 7.8 +/- 1.9 mM to 14.6 +/- 4.0 mM. Addition of GABA also
      affected distribution of carnitine derivatives. The decrease of acetylcarnitine
      level by 1.6 fold was correlated with the inhibition of carnitine
      acetyltransferase (1.77 times). A postulated involvement of this enzyme in
      delivering acetyl moieties for acetylcholine synthesis would suggest a negative
      feedback between GABA and the level of acetylcholine.

PMID- 7646491
TI  - Baculovirus-mediated production of the human growth hormone in larvae of the
      silkworm, Bombyx mori.
AB  - To express the cDNA encoding human growth hormone (hGH) in larvae of Bombyx mori,
      B. mori nuclear polyhedrosis virus (BmNPV) was employed as an expression vector.
      For the construction of the recombinant virus, the hGH cDNA was inserted into the
      downstream of the strong polyhedrin promoter to achieve a high level expression.
      Immunoblot analysis revealed that the virus-mediated hGH was synthesized in the
      larvae and secreted into the hemolymph. The yield of the recombinant hGH
      synthesized in the larvae reached to a level of 160 micrograms/ml of hemolymph
      after purification. The purified recombinant hGH was confirmed to have both the
      same molecular weight and amino acid sequence at its N-terminal region as those
      of the natural counterpart. In addition, the biological activity of the
      recombinant hGH was comparable to that of the natural hGH in the growth
      stimulating effect on rat Nb 2 Node lymphoma cells.

PMID- 7646492
TI  - Modulation of hemopexin gene expression by physiological oxygen tensions in
      primary rat hepatocyte cultures.
AB  - Hyperoxia induces the expression of the hemopexin (Hx) gene in the liver in vivo.
      To investigate whether the Hx gene is activated by oxygen as such or via H2O2 as
      an oxygen signal transmitter the effects of arterial and venous O2 tensions as
      well as different concentrations of H2O2 on Hx mRNA expression were studied.
      After preculturing primary rat hepatocytes for 24 h at arterial O2 (16%) Hx mRNA
      was expressed with a maximal level (= 100%), when arterial O2 tension proceeded
      for 2 h, and to values of approximately 50%, when venous O2 tension (8%)
      proceeded for 2 h. When hepatocytes were precultured for 24 h under venous O2, Hx
      mRNA was induced by arterial O2 to values of 60% and under venous O2 to values of
      approximately 35%. The expression of beta-actin remained unchanged under arterial
      and venous O2. Exposure of hepatocyte cultures to H2O2 decreased the expression
      of Hx mRNA in a dose-dependent manner after 2 h, while heme oxygenase-1 (HO-1)
      mRNA was induced 2.5 fold. The results suggest that O2 per se rather than the
      reactive oxygen intermediate H2O2 modulates Hx expression.

PMID- 7646493
TI  - Characterization of a novel Schizosaccharomyces pombe multidrug resistance
      transporter conferring brefeldin A resistance.
AB  - Brefeldin A disrupts protein secretion and causes the redistribution of the Golgi
      complex to endoplasmic reticulum in both mammalian cells and wild type
      Schizosaccharomyces pombe. We have previously isolated six different genes that,
      when present in multiple copies, confer brefeldin A resistance to wild type S.
      pombe. Here we present the characterization of one of these genes, hba2, which
      encodes a novel S. pombe protein that shares significant sequence similarity to
      members of the ATP-binding cassette superfamily of transport proteins.
      Examination of hba2 expression determined that this gene is overexpressed in
      mutant strains resistant to brefeldin A due to mutations in the negative
      regulator crm1 (bar1) gene or the bar2 gene. The increase of hba2 expression was
      independent of the pap1 transcription factor which is repressed by wild type
      crm1. These results suggest that crm1 negatively regulates multiple transcription
      factors including one that modulates hba2 transcription.

PMID- 7646494
TI  - Beta-scorpion toxin 2 from Centruroides noxius blocks voltage-gated K+ channels
      in human lymphocytes.
AB  - Using the patch-clamp technique, we determined that beta-scorpion toxin 2 from
      Centruroides noxius Hoffmann decreased whole-cell n-type K+ currents in human
      peripheral blood lymphocytes, with a half blocking concentration of approx. 5
      microM. Toxin-2-accelerated inactivation, however, did not influence the kinetics
      of activation of the K+ conductance. The percentage increase in K+ channel
      inactivation rate and the degree of drug-induced block was independent of
      membrane potential. K+ channel block by Toxin 2 was instantaneous, not removable
      by washing with drug free extracellular solution. However, 10 mg/ml BSA in the
      bath lifted the toxin-induced block almost instantaneously and completely. Flow
      cytometric membrane potential measurements with the oxonol dye showed that Toxin
      2 depolarizes human lymphocytes in concert with its K+ channel blocking effect.

PMID- 7646495
TI  - O-linked N-acetylglucosamine is upregulated in Alzheimer brains.
AB  - We present evidence that the expression of the novel intracellular carbohydrate
      modification of proteins--O-glycosidically linked N-acetylglucosamine (O-GlcNAc)-
      is significantly upregulated in Alzheimer brains over that of age matched control
      brains. This increase is specific for proteins associated with the detergent
      insoluble cytoskeleton and not for proteins of the detergent soluble fraction and
      is not due to an increase in protein expression in this fraction. The possible
      involvement of abnormal phosphorylation in the disease state and the interplay
      between phosphorylation and the O-GlcNAc modification suggests that the increased
      level of intracellular O-GlcNAc expression may be implicated in the pathogenesis
      of Alzheimer's disease.

PMID- 7646496
TI  - Extensive tissue oxygenation associated with mitochondrial DNA mutations.
AB  - Extensive tissue oxygenation in the mitochondrial myopathy patients caused by the
      mitochondrial DNA mutations was first demonstrated noninvasively by a tissue
      oxymeter measuring near infrared light. The extent of oxygenation of the tissue
      due to dysfunction of mitochondria correlated with the seriousness of
      mitochondrial DNA mutations resulting in defects in oxidative phosphorylation
      system, and causing suppressed oxygen utilization. Such oxygen stress furthers
      mitochondrial DNA mutations during the progressive course of the disease. This
      noninvasive diagnosis will find useful application in the diagnosis and
      management of patients of advanced age.

PMID- 7646497
TI  - Biradicals as ESR probes of conformations in model beta-turn peptides.
AB  - Electron spin-spin exchange interaction in biradicals has been examined for its
      potential usefulness in the conformational analysis of peptides in solution.
      Three peptides with high propensity to adopt beta-turn conformations in solution,
      Boc-Cys-Pro-Xxx-Cys-NHMe (Xxx = Leu, 1; Xxx = Aib, 2; Xxx = Tyr, 3), have been
      modified into biradicals by spin labeling the thiols groups. Analysis of electron
      spin resonance spectra of these peptides in a variety of solvents and at
      different temperatures suggests that the population of folded conformations
      follows the order 2 > 1 > 3.

PMID- 7646498
TI  - Transport of L-arginine in arginine-deprived endothelial cells.
AB  - In vascular endothelium, L-arginine (ARG) plays a crucial role as a substrate for
      various metabolic pathways, one of which is the synthesis of bioregulatory nitric
      oxide. Transport of ARG across the cell membrane determines intracellular
      substrate availability. Membranous transport in turn may be dependent on the
      extra-to-intracellular gradient in ARG concentration. To test this hypothesis ARG
      transport was characterized in control and ARG-deprived endothelial cells (EC).
      Within a two-hour deprivation period a decrease of more than 50% in intracellular
      ARG concentration was observed. Initial uptake rates for ARG revealed no
      significant differences between ARG-deprived and control EC (30.0 +/- 2.7 vs.
      30.6 +/- 2.1 pmol*(mg protein*min)-1). Two distinct ARG transporter components
      were observed dependent on extracellular ARG concentration. No significant
      differences between ARG-deprived and control EC were found with respect to the
      kinetics of these ARG transporter components. The present data suggest that in
      this model the transport rate of ARG into EC is not directly dependent on the
      intracellular ARG concentration. Thus, a feedback loop between intracellular ARG
      concentration and ARG transporters as a critical determinant for endothelial ARG
      dependent pathways such as NO-synthesis appears highly unlikely.

PMID- 7646499
TI  - Sequencing of the tuf1 gene and the phosphorylation pattern of EF-Tu1 during
      development and differentiation in Streptomyces collinus producing kirromycin.
AB  - We have cloned and sequenced the tuf1 gene from a kirromycin-producing strain of
      Streptomyces collinus. The gene encodes a polypeptide of 396 amino acid residues
      with a molecular weight of 43,849. The protein shows 97% identity with EF-Tu1 of
      S. coelicolor and is sensitive to kirromycin. EF-Tu-dependent translation of
      poly(U) was reduced to 50% in the presence of 0.25 microM kirromycin. Using high
      resolution two-dimensional electrophoresis and specific immunodetection with
      monoclonal antibodies we found that the EF-Tu1 is phosphorylated on threonine and
      that serine is the second phosphate-accepting amino acid. EF-Tu1 phosphorylated
      on threonine and serine residues was detected among the S150 supernatant proteins
      of vegetative cells, aerial mycelium and spores. The level of phosphorylated EF
      Tu1 varied during the growth and differentiation.

PMID- 7646500
TI  - Expression of syntaxin 4 in rat skeletal muscle and rat skeletal muscle cells in
      culture.
AB  - Syntaxins are a family of membrane proteins believed to participate in
      docking/fusing of arriving vesicles during membrane sorting and secretion. Of the
      six mammalian syntaxins known, only brain syntaxin 1A/1B has been biochemically
      characterized in its endogenous form. Syntaxin 4 mRNA is expressed in selective
      tissues including rat skeletal muscle, although it has not been studied at the
      protein level in any cell type. Therefore, we generated an affinity-purified
      antibody against syntaxin 4 to demonstrate that this 36 kDa protein is expressed
      in rat skeletal muscle and L6 muscle cells in culture. The content of the
      syntaxin 4 protein increased by 1.9-fold during differentiation of L6 myoblasts
      into myotubes. By subcellular fractionation the protein was mainly recovered in
      plasma membrane-enriched fractions of both red and white skeletal muscles and L6
      myotubes. Coupled to the recent detection of vesicle associated membrane protein
      2 and cellubrevin in skeletal muscle, syntaxin 4 may play a role in membrane
      traffic in this tissue.

PMID- 7646501
TI  - Direct evidence for quinone-quinone methide tautomerism during tyrosinase
      catalyzed oxidation of 4-allylcatechol.
AB  - The hapatotoxicity of safrole and related compounds has been attributed to the
      electrophilic compounds generated from the oxidation of these chemicals. In this
      paper, for the first time using quasi pre-steady state conditions, we present
      direct evidence for the rapid production of electrophilic allyl o-quinone and its
      tautomerization to more stable and reactive vinyl p-quinone methide during both
      the enzyme catalyzed and chemical mediated oxidation of 4-allylcatechol, an in
      vivo product of safrole metabolism.

PMID- 7646503
TI  - Detection and expression of the 70 kDa heat shock protein SSB1P at different
      temperatures in Saccharomyces cerevisiae.
AB  - Ssb1p and ssb2p are two members of the hsp70 family in yeast. Up to now there has
      been no evidence to indicate any differences between these two members of the
      hsp70 family, and it was suggested that ssb1p and ssb2p were 99% identical. Here
      we show that an antibody prepared against the C-terminal domain of human hsp71
      recognizes specifically ssb1p out of the eight hsp(c)70s in Saccharomyces
      cerevisiae. An amino acid peptide sequence at the C-terminal end (VTATDKSTGK) is
      suggested to be the sequence which has high homology between ssb1p and hu-hsp71
      and to be responsible for the specificity of recognition of this unique member of
      the hsp70 family. Using this antibody in immunoblot assays, we have determined
      the cellular content of ssb1p after heat shock and at different growth
      temperatures. Ssb1p is shown to be degraded during heat shock treatment while it
      shows a higher level of expression at low temperatures.

PMID- 7646502
TI  - Vibrio mimicus arylesterase has thioesterase and chymotrypsin-like activity.
AB  - A Vibrio mimicus serine arylesterase and an Escherichia coli thioesterase/serine
      protease share 49.4% amino acid identity. The arylesterase has thioesterase
      activity for benzoyl-CoA and chymotrypsin-like activity for N-carbobenzoxy-L
      phenylalanine p-nitrophenyl ester (NBPNPE). The gene encoding the V. mimicus
      enzyme is designated etpA. Substituting Ser31 of the V. mimicus enzyme with a
      glycine or an alanine altered its activity. In comparison with wild type enzyme,
      the S31A enzyme showed a 5-fold increase and 57% decrease in the catalytic
      efficiency for benzoyl-CoA and NBPNPE, respectively, and the S31G enzyme showed a
      3.6-fold increase and 43% decrease in the catalytic efficiency for benzoyl-CoA
      and NBPNPE, respectively. For the two mutant enzymes an 8-fold decrease and a 6-
      to 7-fold increase in Km were seen for benzoyl-CoA and NBPNPE, respectively. The
      mutagenesis results prove that residue 31 plays an important role in the
      substrate-specificity.

PMID- 7646504
TI  - Melanotropin and corticotropin are encoded on two distinct genes in the lamprey,
      the earliest evolved extant vertebrate.
AB  - In the lamprey, which is a member of the oldest extant class of vertebrates, the
      agnathans, melanotropins (MSH) and corticotropin (ACTH) were found to be encoded
      on two distinct genes. In all other vertebrates, a single precursor gene,
      proopiomelanocortin (POMC), encodes MSH and ACTH, as well as beta-endorphin
      (END). Two different cDNAs were cloned from a lamprey pituitary lambda gt11 cDNA
      library using antisera against lamprey MSH-B and ACTH(1-16). One cDNA encoded MSH
      B, MSH-A and beta-END, while the other cDNA encoded nasohypophysial factor (NHF),
      ACTH and a different beta-END, but not MSH-A and MSH-B. Northern blot analysis
      demonstrated that in the adult lamprey pituitary, genes for MSH and ACTH are
      expressed in the pars intermedia (PI) and pars distalis (PD), respectively.

PMID- 7646506
TI  - Sarcolemmal chloride and potassium channels from normal and myotonic mouse muscle
      studied in lipid supplemented vesicles.
AB  - By patch-clamp analysis of lipid supplemented vesicles prepared from the
      sarcolemma of mouse wildtype skeletal muscle, we could identify two known types
      of potassium channels, the inward rectifier and Ca2+ activated BK channels, and
      five types of chloride channels designated CIC-a, CIC-b, CIC-c, CIC-d, and CIC-e.
      CIC-b corresponds to a known chloride channel, whereas CICa, -c, -d and -e have
      not been described previously. The diversity may be due to a heterooligomeric
      composition of different subunits. None of these chloride channels nor the
      potassium channels were found in the sarcoplasmic reticulum fraction. In vesicles
      from myotonic mice, Clc-d and -e were not found.

PMID- 7646505
TI  - Cyclic cholecystokinin-analog pentapeptide cyclo (Asp-Trp-Met-Asp-Phe): an
      unexpected solution conformation.
AB  - The conformational analysis of the CCK-B binding peptide cyclo (Asp-Trp-Met-Asp
      Phe) has been carried out in DMSO-d6 and in a mixture of H2O/DMSO-d6 by NMR
      spectroscopy and by restrained molecular dynamics methods. In the NMR spectra,
      only one set of resonance signals was found. The NOE analyses proved the
      existence of an all-trans conformation for this peptide. Distance constraints of
      1H pairs derived from NOE data were used for restrained molecular dynamics
      simulations, resulting in one conformational family with a very regular
      orientation of the amino acids and similar dihedral angles for each residue. The
      dihedrals and the absence of an intramolecular hydrogen bond indicate that there
      is no common turn formation in the peptide backbone. A submicromolar binding
      constant for CCK-B receptors point to a similarity with the bioactive
      conformation.

PMID- 7646507
TI  - Isolation of a novel RFamide peptide from the midgut of the American cockroach,
      Periplaneta americana.
AB  - In insects (FM)RFamide-immunoreactive endocrine cells are ubiquitously present in
      the midgut, but the identity of the peptide(s) produced by these cells is
      unknown. The major RFamide-immunoreactive peptide from the midgut of the American
      cockroach, Periplaneta americana, was isolated and identified as Ala-Asn-Arg-Ser
      Leu-Arg-Leu-Arg-Pheamide. This is a novel member of an arthropod peptide family,
      previously known only from mosquitoes and horseshoe crabs. Its abundance in the
      midgut suggests that it plays an important function in digestion.

PMID- 7646508
TI  - Full antitumor action of recombinant seminal ribonuclease depends on the removal
      of its N-terminal methionine.
AB  - Bovine seminal RNase (BS-RNase) is a dimeric member of the pancreatic-like
      ribonuclease superfamily, with antitumor activity. We report here that
      recombinant Met(-1) BS-RNase is a less potent cytotoxic factor, while
      structurally and catalytically indistinguishable from BS-RNase isolated from
      natural sources. Mature recombinant BS-RNase instead displays full antitumor
      action. This suggests that the conformation of the N-terminal region of BS-RNase
      is among the structural determinants of its antitumor action, in addition to its
      catalytic activity and its quaternary structure.

PMID- 7646509
TI  - Insulin-dependent regulation of Glut4 gene expression in ventricular
      cardiomyocytes: evidence for a direct effect on Glut4 transcription.
AB  - The present study examined the effect of insulin on Glut4 transcription in
      isolated ventricular cardiomyocytes. Upon exposure to the hormone (2 x 10(-7) M)
      the cellular Glut4 mRNA content increased to 224 +/- 46% of control within 3.5
      hours. Nuclear run-on analysis indicated a parallel increase of transcription of
      the Glut4 gene to 208 +/- 49% of control. Direct incubation of cardiac nuclei
      with insulin resulted in a comparably significant increase of Glut4
      transcription. Cross-linkage experiments with 125I-labelled insulin demonstrated
      the absence of soluble nuclear insulin receptors, which were readily detected in
      plasma and microsomal membranes. These findings suggest that expression of the
      cardiac Glut4 gene is subject to regulation by insulin at the transcriptional
      level, a process possibly involving nuclear association of the hormone.

PMID- 7646511
TI  - Effects of submaxillariectomy on ovarian androgen and estrogen production in
      adult female rats.
AB  - Submaxillariectomy causes an increase in uterine weight in adult female rats.
      This increase is due to the elevation of the plasma 17 beta-estradiol (E2) level
      which is brought on by enhancement of ovarian E2 production. Furthermore,
      enhancement of ovarian E2 production is due to the enhancement of testosterone
      and androstenedione production which are the precursors of ovarian E2. However,
      submaxillariectomy did not affect ovarian progesterone and 17 alpha
      hydroxyprogesterone levels. These findings suggest that the submaxillary gland
      may inhibit the production of ovarian E2 mainly because of the inhibition of
      ovarian androgen production. Thus the submaxillary gland may play a physiological
      role in female reproductive systems caused by the change in ovarian
      steroidogenesis.

PMID- 7646510
TI  - Selection and partial characterization of calcium ionophore (A23187) resistant
      cells.
AB  - We have selected calcium ionophore (A23187)-resistant cells (AR-7) in a human
      promyelocytic leukemia cell line, HL-60. AR-7 showed approximately 8.5-fold
      resistance to A23187 compared with the wild type cells after continuous exposure
      for 3 days. AR-7 had cross resistance to ionomycin (4.6-fold) and thapsigargin
      (340-fold) which can also increase intracellular Ca++. Similar magnitude of
      resistance to apoptosis, as defined by characteristic morphology and
      internucleosomal DNA fragmentation, induced by these agents was observed after 4
      hr of incubation. However, both the elevation of intracellular Ca++ following
      stimulation with various concentrations of A23187 and the sensitivity to anti
      cancer agents including etoposide, 1-beta-D arabinofuranosylcytosine, and
      hydroxyurea were comparable between the two cell types. This cell line is
      considered to be useful for exploring the mechanism(s) of cell death, especially
      apoptosis, induced by calcium ionophore.

PMID- 7646513
TI  - Human aldehyde dehydrogenase E3 isozyme is a betaine aldehyde dehydrogenase.
AB  - The E3 isozyme of human aldehyde dehydrogenase (EC 1.2.1.3), with broad substrate
      specificity, which also catalyzes dehydrogenation of 4-aminobutyraldehyde, was
      purified and sequenced recently (1,3). It has been shown during this
      investigation to have betaine aldehyde dehydrogenase activity. Betaine aldehyde
      and 4-aminobutyraldehyde activities copurified on six chromatographic columns.
      Molecular properties of the homogeneous product were identical with those of E3
      isozyme. Activity with betaine aldehyde was considerably higher than that with 4
      aminobutyraldehyde, the best known substrate. Thus, human E3 isozyme and betaine
      aldehyde dehydrogenase (EC 1.2.1.8) are the same enzyme.

PMID- 7646512
TI  - The MEF2B homologue differentially expressed in mouse embryonal carcinoma cells.
AB  - The MEF2 gene family encodes a MADS-box transcription factor which regulates
      expression of many muscle-specific genes. We examined the expression of the MEF2
      genes in mouse embryonal carcinoma P19 cells before and after in vitro muscle
      differentiation induced by dimethyl sulfoxide (DMSO). At least three different
      MADS/MEF2 domains (MEF2A, 2B and 2D) were isolated from P19 cells with the MOPAC
      technique (mixed oligonucleotides primed amplification of cDNA). Although two of
      the MADS/MEF2 domain sequences were identical to those of human MEF2A and MEF2D,
      another domain sequence was similar but not identical to that of human MEF2B.
      While the transcription of MEF2A and MEF2D was up-regulated during
      differentiation of P19 cells, the MEF2B homologue was abundantly transcribed in
      undifferentiated P19, F9 and ES cells and down-regulated in adult heart, skeletal
      muscle or brain, suggesting that the murine MEF2B homologue might have a function
      distinct from other members of the MEF2 gene family in embryogenesis and
      development.

PMID- 7646514
TI  - RNA signals for translation frameshift: influence of stem size and slippery
      sequence.
AB  - The pol gene of HIV-1 is expressed as a fusion protein with the upstream gag gene
      product after -1 ribosomal frameshifting. To get insights into the sequence
      requirements for the slippery heptanucleotide, generally present at the
      frameshift junction, and the downstream stem-loop structure, we prepared,
      starting from the gag-pol boundary sequence of HIV-1, serial deletion and base
      substitution derivatives for both of these signals, and inserted them into the
      amino-terminal proximal region of the luciferase gene, but downstream of the
      initiation codon, in out-of-frame fashion. The results of in vitro translation
      studies indicate that the stem-loop is not essential even if its size influences
      the efficiency of ribosomal frameshifting, and that the optimum repetition number
      of a single nucleotide within the slippery sequence exists for efficient
      ribosomal frameshifting.

PMID- 7646515
TI  - Design of noncovalent trypsin inhibitor based on the X-ray crystal structure of
      the complex.
AB  - The inhibitory mechanism of trans-4-aminomethylcyclohexanecarbonyl-L-phenyl
      alanine-4-carbo xymethylanilide (1), a noncovalent serine protease inhibitor
      synthesized based on previous structure-activity studies, was clarified based on
      the X-ray crystal structure of the complex (2.2 A resolution, R = 0.175), where
      the amino group of the aminomethylcyclohexane moiety was bifurcately hydrogen
      bonded to the carboxyl oxygens of Asp 189 side group (specificity pocket), and
      the hydrogen bonds of the cyclohexanecarbonyl oxygen to NHs of Gly 193 and Ser
      195 residues (oxyanion hole) and of Phe NH to Ser 195 O gamma atom (catalytic
      triad) were observed. In contrast, the Phe benzene moiety and terminal
      carboxymethylanilide of 1 were not well located on the electron density map,
      suggesting the conformational freedom of these P1' and P2' sites at the binding
      pocket. Based on these insights, trans-4-aminomethylcyclohexanecarbonyl-4-nitro-L
      phenylalanine-4-+ ++benzoylanilide (2) was designed, in which the P1' and P2'
      sites were modified so as to effectively interact with the amino acid residues of
      trypsin binding pocket via hydrogen bonding and van der Waals interactions,
      respectively. Consequently, 2 showed 40 times higher inhibitory activity against
      trypsin than 1.

PMID- 7646516
TI  - A novel mtDNA point mutation in maternally inherited cardiomyopathy.
AB  - A novel mtDNA mutation at position nt. 4300 in the tRNAIle gene is associated
      with hypertrophic cardiomyopathy inherited as a maternal trait. Interestingly,
      this mutation seems to cause a pure heart disease as opposed to most other mtDNA
      mutations, which are associated with multisystemic disorders. Hypertrophic
      cardiomyopathies are genetically heterogeneous, and mtDNA defects should be
      considered in the differential diagnosis, especially when there is evidence of
      maternal inheritance.

PMID- 7646517
TI  - Non-peptide bombesin receptor antagonists, kuwanon G and H, isolated from
      mulberry.
AB  - Kuwanon G and H, isolated from the methanol extract of Morus bombycis, inhibited
      specific binding of [125I]gastrin-releasing peptide (GRP) to GRP-preferring
      receptors in murine Swiss 3T3 fibroblasts with Ki values of 470 and 290 nM,
      respectively. Kuwanon H was one order of magnitude less potent for inhibiting
      [125I]bombesin binding to neuromedin B (NMB)-preferring receptors in rat
      esophagus membranes. This compound antagonized bombesin-induced increases in the
      cytosolic free calcium concentration and GRP-induced DNA synthesis in Swiss 3T3
      cells. Thus, kuwanon H, and possibly kuwanon G also, are specific antagonists for
      the GRP-preferring receptor and can be useful for studying the physiological and
      pathological role of GRP.

PMID- 7646518
TI  - Endogenous interleukin 10 prevents apoptosis in macrophages during Salmonella
      infection.
AB  - To elucidate the biological roles of endogenous interleukin 10 (IL-10) in
      macrophage responses during bacterial infection, we examined in vitro effects of
      neutralizing IL-10 by anti-IL-10 monoclonal antibodies (mAb) on apoptosis of the
      peritoneal macrophages following Salmonella choleraesuis infection. Marked
      increments of TNF-alpha production were observed in the culture supernatant later
      than 6 h after in vitro culture with anti-IL-10 mAb. These macrophages succumbed
      to apoptosis at this stage accompanied by marked increment of IL-1 release,
      despite the expression of higher amount of endogenous heat shock protein 70, an
      inhibitor of TNF-alpha-mediated apoptosis. These results suggest that endogenous
      IL-10 plays an essential role in protection of Salmonella-infected macrophages
      from autocrine suicide caused by excessive production of TNF-alpha after killing
      of Salmonella.

PMID- 7646519
TI  - Reduced level of octamer binding transcription factor (Oct-1) is correlated with
      H2B histone gene repression during differentiation of HL-60 cells by all-trans
      retinoic acid.
AB  - To gain insight on the role of transacting factors in the regulatory mechanism of
      H2B histone gene expression during the differentiation of HL-60 cells by all
      trans retinoic acid (retinoic acid), the binding pattern of the nuclear proteins
      to various elements in the human H2B histone upstream region has been
      investigated with DNase I footprinting and DNA mobility shift assay. The level of
      H2B histone mRNA was markedly reduced at 48 hr in retinoic acid-treated HL-60
      cells. The H2B histone mRNA was repressed in proportion to the concentration of
      retinoic acid. In DNase I footprinting analysis, a nuclear factor (octamer
      binding transcription factor, Oct-1) bound at -42 bp (ATTTGCAT) both before and
      after retinoic-acid-induced differentiation of HL-60 cells. One DNA-protein
      complex was formed by DNA mobility shift assay, and the level of Oct-1 decreased
      during retinoic-acid-induced differentiation. In the cycloheximide-treated HL-60
      cells, the level of Oct-1 also reduced. These results suggest that the
      transcriptional repression of H2B histone gene during retinoic-acid-induced
      differentiation in HL-60 cells may be mediated by reduced level of Oct-1.

PMID- 7646520
TI  - Circadian variations of prostaglandins D2, E2, and F2 alpha in the cerebrospinal
      fluid of anesthetized rats.
AB  - Circadian variations in the levels of prostaglandins (PGs) D2, E2, and F2 alpha
      were studied in the cerebrospinal fluid (CSF) of rats. We collected CSF samples
      from the cisterna magna of anesthetized rats at different clock-hours (1000,
      1400, 1800, 2200, 0200, and 0600 hr), and measured the concentrations of the
      three PGs. PGD2, which appeared to be the most abundant among the three, showed a
      circadian variation; and the mean of the day-time levels (145 pg/ml) was
      significantly higher than that of the nighttime ones (111 pg/ml). Day/night
      variations were also noticed with the levels of PGE2 and PGF2 alpha; however,
      these levels remained 3-4 times lower than those of PGD2. The general day/night
      variation seen in the CSF concentration of PGD2 conforms well with the postulated
      role of PGD2 as an endogenous sleep-promoting factor acting on a certain brain
      surface area defined as its site of action.

PMID- 7646521
TI  - Osteoblast-like cell adherance and migration through 3-dimensional porous polymer
      matrices.
AB  - Osteoblast cells collected from rat calvaria were plated onto a biodegradable 3
      dimensional porous composite of poly(lactide-co-glycolide) and hydroxyapatite to
      quantitatively assess the matrix's ability to support living cell adhesion
      throughout an initial 24 hour period. Numbers of cells adhering to the polymer
      exceeded the plating number of cells, demonstrating that during the 24 hour
      period, proliferation of cells began. Using immunofluorescent staining for anti
      osteocalcin, an exclusive marker for bone cells, osteoblasts were seen to adhere
      to both the exterior surface of the polymer and to have migrated to the interior
      surface of the matrix. It is proposed that this biodegradable cell/polymer
      composite may be useful in bone grafting applications. These studies demonstrated
      early cellular attachment, proliferation and ingrowth of osteoblast cells can
      occur within the matrix, with preservation of bone cell phenotypes.

PMID- 7646522
TI  - Synthesis of caged compounds of L-leucyl-L-leucine methyl ester, an apoptosis
      inducer, and their cytotoxic activity.
AB  - In this study, we newly synthesized caged compounds of L-leucyl-L-leucine methyl
      ester and examined their photochemical and immunological properties. From the
      viewpoints of solubility in phosphate-buffered saline containing 1% dimethyl
      sulfoxide as well as photoreactivity, we chose two caged compounds, 1 and 2, for
      study. Upon irradiation, L-leucyl-L-leucine methyl ester with a trans-o
      hydroxycinnamoyl group (1) releases L-leucyl-L-leucine methyl ester quite slowly,
      whereas L-leucyl-L-leucine methyl ester with an o-nitrobenzyl group (2) releases
      L-leucyl-L-leucine methyl ester quickly. Both irradiated compounds induced
      apoptosis of U937 cells, as evidenced by a decrease in cell size, although 1
      itself caused necrosis (cell swelling) of these cells.

PMID- 7646523
TI  - Evolutionary reengineering of the phosphofructokinase active site: ARG-104 does
      not stabilize the transition state in 6-phosphofructo-2-kinase.
AB  - Arg-104 of the kinase domain of 6-phosphofructo-2-kinase/fructose 2,6
      bisphosphatase was mutated to alanine, the mutant enzyme expressed in E. coli
      with a T7 RNA polymerase-based expression system, and purified to homogeneity by
      Blue-Sepharose and Q-Sepharose chromatography. The mutant enzyme exhibited a 200
      fold increase in Km for fructose-6-phosphate, no change in Km for ATP, and a 2-3
      fold increase in catalytic rate. The results indicate that Arg-104, along with
      Arg-195, are the principal binding site residues for the 6-phosphate group of
      fructose-6-phosphate. In contrast to the corresponding residue in the related E.
      coli 6-phosphofructo-1-kinase, Arg-104 did not stabilize the transition state at
      pH 7-9. The Arg-104 mutation also decreased Fru-2,6-P2ase activity without
      affecting substrate inhibition, which suggests that this mutation affects the
      bisphosphatase active site conformation and/or substrate access to it.

PMID- 7646524
TI  - Receptor-mediated toxicity to pericytes of advanced glycosylation end products: a
      possible mechanism of pericyte loss in diabetic microangiopathy.
AB  - The influence of advanced glycosylation end products (AGE) on bovine retinal
      pericytes was investigated. When pericytes were cultured with AGE-bovine serum
      albumin (BSA), pericyte growth was significantly retarded in a dose-dependent
      manner. They also exhibited an immediate toxicity to pericytes. However, MRC-5
      human fibroblasts were totally resistant to AGE-BSA. Moreover, antisense
      oligonucleotides complementary to mRNA coding for AGE receptor were found to
      reverse the AGE-induced decrease in viable pericyte number, although the mRNA
      level was about one order of magnitude lower in pericytes than in the
      fibroblasts. These results indicate that pericytes may possess a peculiar
      sensitivity to AGE, and that AGE ligand-receptor interactions may play an
      important role in the pathogenesis of pericyte loss, the principal change in
      diabetic microangiopathies.

PMID- 7646525
TI  - Parathyroid hormone stimulates electrogenic sodium transport in A6 cells.
AB  - The effects of parathyroid hormone (PTH) on sodium homeostasis in the distal
      tubule are not well defined. Using A6 cells as a model for distal tubular
      epithelium we measured equivalent short circuit current (leq), as an estimate of
      net sodium transport. We found that PTH increased leq in a dose-dependent manner.
      DDA, an agent which inhibits adenylate cyclase, decreased PTH-activated sodium
      transport, suggesting a role for cAMP elevation in PTH effects. Moreover,
      addition of Rp-cAMP, an inhibitor of cAMP-dependent protein kinase, partially
      blocked the PTH-stimulated leq. PTH also elicited a sustained increase in [Ca2+]i
      in A6 cells. This elevation in [Ca2+]i was abolished by removal of calcium from
      the extracellular medium, suggesting the involvement of calcium influx pathways.
      In fact, addition of the calcium channel blocker nitrendipine to PTH-stimulated
      leq partially blocked PTH-activated sodium transport. Taken together these data
      demonstrate that PTH stimulates electrogenic sodium transport in A6 cells and
      that this effect may be mediated through a rise in both intracellular calcium and
      cellular cAMP.

PMID- 7646526
TI  - Characterization of gene regulatory elements for selective gene expression in
      human melanoma cells.
AB  - Since chemotherapy is not sufficiently effective, an alternative strategy for the
      treatment of advanced melanoma could be an in vivo gene therapy approach. For
      this purpose, a highly accurate delivery of the therapeutic gene and cell
      specific gene expression is essential. Since melanocytic cells are characterized
      by their pigmentation, and since tyrosinase is the key enzyme involved in
      melanogenesis, we studied the expression of a reporter gene which is under the
      control of the tyrosinase promoter or a combination of melanocyte-specific
      enhancer and tyrosinase promoter in ten human melanoma and four epithelial cell
      lines. Reporter gene expression was upregulated up to 21-fold using the
      tyrosinase promoter and up 154-fold using the enhancer/promoter construct
      compared to a control plasmid. Gene expression was strongly associated with
      capacity of cells for melanin synthesis. The results suggest that the use of
      tissue specific gene regulatory elements might provide a new opportunity for
      targeting therapeutic genes to melanoma cells.

PMID- 7646527
TI  - Effects of vitamin A deficiency and retinoic acid treatment on expression of a
      phosphoenolpyruvate carboxykinase-bovine growth hormone gene in transgenic mice.
AB  - Vitamin A regulation of specific promoter domains of the phosphoenolpyruvate
      carboxykinase (PEPCK) gene was tested in a PEPCK/bovine growth hormone (bGH)
      transgenic mouse model. Vitamin A deficiency causes a significant decrease in
      hepatic bGH mRNA when expression is driven by either a 533-base-pair (bp) PEPCK
      promoter fragment (from position -460 to +73) or a 428-bp PEPCK promoter fragment
      (from position -355 to +73). Treatment of vitamin A deficient transgenic mice
      with all-trans retinoic acid (RA) increases bGH mRNA levels above those measured
      with the deficiency. Hepatic retinoic acid receptor (RAR)beta mRNA levels also
      change with vitamin A deficiency and supplementation, but not RAR alpha mRNA
      levels. These results indicate that all-trans RA plays a physiologic role in
      regulating expression of a gluconeogenic gene in liver.

PMID- 7646528
TI  - Primary structure of BMK1: a new mammalian map kinase.
AB  - Mitogen-activated protein (MAP) kinases comprise a family of conserved,
      eukaryotic enzymes that mediate responses to a wide variety of extracellular
      stimuli. We have identified a new human MAP kinase gene here termed BMK1. BMK1
      encodes a protein of 816 amino acid residues and has at least three different
      forms of mRNA. BMK1 messages are abundant in heart, placenta and kidney but not
      detectable in liver. Although BMK1 has the dual phosphorylation site of MAP
      kinases characterized by the TEY sequence found in ERK1 and ERK2, it has a
      distinct C-terminal and loop-12 structure when compared to other mammalian MAP
      kinases. This suggests BMK1 may regulate signaling events distinct from those
      controlled by the ERK group of enzymes.

PMID- 7646529
TI  - A simple molecular assay for the C1166 variant of the angiotensin II type 1
      receptor gene.
AB  - Studies of human polygenic diseases require the genotyping of polymorphic markers
      from large numbers of subjects. The rapid detection of the insertion
      (I)/deletion(D) polymorphism of the angiotensin converting enzyme (ACE) gene by
      the polymerase chain reaction (PCR) has facilitated the study of this locus in a
      a number of cardiovascular diseases, but not all gene polymorphisms are as easily
      detected. We describe a rapid mismatch-PCR/restriction fragment length
      polymorphism (RFLP) assay for the C1166 variant of the angiotensin II type 1
      receptor gene, a mutation which may interact with the ACE polymorphism in the
      determining of risk of myocardial infarction. This rapid assay, which requires no
      special equipment or expertise, will be useful in confirming the interaction
      between these two gene loci. The principles utilised can be applied more
      generally to the detection of any polymorphic single base substitution.

PMID- 7646530
TI  - Expression of glycosylphosphatidylinositol-anchored NAD glycohydrolase in
      differentiated HL60 cells by phorbol ester.
AB  - Human leukemic HL60 cells are known to express NAD glycohydrolase (NADase)
      activity following differentiation into macrophage-like cells by 12-O
      tetradecanoylphorbol-13-acetate (TPA) or granulocyte-like cells by retinoic acid
      (RA) treatment. Recently, it was reported that 46 kDa human leukocyte antigen,
      CD38, expressed by RA-differentiated HL60 cells contained NADase, ADP-ribosyl
      cyclase and cyclic ADP-ribose hydrolase activities. In the present study we
      questioned whether the NADase activity found in TPA-differentiated HL60 cells is
      similar to that found in RA-treated cells. Herein we demonstrate that, unlike
      what is observed following RA treatment, the NADase activity of TPA
      differentiated cells associates with a 65 kDa glycosylphosphatidylinositol
      anchored NADase.

PMID- 7646531
TI  - Somatostatin analogs: clinical application in relation to human somatostatin
      receptor subtypes.

PMID- 7646532
TI  - Extra-nuclear location of histones in activated human peripheral blood
      lymphocytes and cultured T-cells.
AB  - Dextrin-2-sulphate (D2S) is a sulphated polysaccharide which inhibits human
      immunodeficiency virus type 1 infection of T-cells by binding to the cell
      surface. During our investigations of the nature of this interaction, a cell
      membrane fraction was prepared by ultracentrifugation from the T-cell line, HPB
      ALL. Separation of membrane proteins by sodium dodecyl sulphate (SDS)
      polyacrylamide gel electrophoresis and analysis for binding proteins using ligand
      blotting showed that 3H-D2S bound, in a saturable and displaceable manner, to two
      regions corresponding to molecular weights of 14,000-18,000 and 28,000-32,000.
      The N-terminal sequences of two of the major protein components in the 14,000
      18,000 region were consistent with those of histones H2B and H3. The presence of
      histone H2B in the cell membrane preparation was confirmed by immunoblotting and
      enzyme-linked immunosorbent assay using a specific antibody. Histone standards
      were used to determine the level of each histone in the cell membrane fraction.
      In addition, the binding of 3H-D2S to purified histone standards was quantified.
      These results show that all of the binding of 3H-D2S to proteins in the 14,000
      18,000 region of the cell membrane preparation can be attributed to the histones
      present. In contrast to HPB-ALL cells, a cell membrane fraction from freshly
      isolated human peripheral blood lymphocytes contained very low levels of
      histones. However, after culture with phytohaemagglutinin for 3 days the cell
      membrane fraction contained greatly increased levels of histones. To exclude the
      possibility of contamination of the cell membrane preparation with histones
      derived from the nucleus, cell membranes were also prepared using an affinity
      based method using polyethyleneimine-cellulose. Immunoblotting of adsorbed plasma
      membranes showed the presence of histone H2B. SDS-polyacrylamide gels stained for
      protein also indicated that the preparation contained histones H1, H2A, H3 and
      H4. In further experiments whole cells were used to avoid contamination from
      nuclear proteins. Lactoperoxidase mediated 125I labelling, a method specific for
      radiolabelling cell surface proteins, confirmed the presence of histones H2B, H3
      and H4 on the surface of HPB-ALL cells. Also, incubation of HPB-ALL cells or
      phytohaemagglutinin-activated peripheral blood lymphocytes with D2S caused
      displacement of histones from the cell surface into the supernatant without
      altering cell viability. In addition, immunocytochemistry of freshly isolated
      peripheral blood lymphocytes showed that histone H2B was located predominantly in
      the nucleus. However, in phytohaemagglutinin-activated peripheral blood
      lymphocytes immunoreactive material was also prominent in the endoplasmic
      reticulum and on the plasma membrane.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7646534
TI  - Functional coupling of dopamine D2 and muscarinic cholinergic receptors to their
      respective G proteins assessed by agonist-induced activation of high-affinity
      GTPase activity in rat striatal membranes.
AB  - Agonist-induced high-affinity GTPase activity was investigated using the crude
      membrane preparation from rat striatum. High-affinity GTPase activity was
      stimulated by dopamine and carbachol in a Mg(2+)-dependent manner and with
      possible optimum NaCl concentrations of 50-100 mM to detect the percent increase
      induced by each agonist. Dopamine and selective (as well as non-selective) D2
      receptor agonists, but not selective D1 receptor agonists, stimulated activity in
      a concentration-dependent manner, with affinities which were significantly
      correlated with those for adenylate cyclase inhibition as previously reported in
      the literature. Maximal percent stimulation above basal high-affinity GTPase
      activity was 9.8 +/- 0.6% and 4.4-7.6% for dopamine and other synthetic dopamine
      D2 receptor agonists, respectively. Dopamine-stimulated activity was inhibited by
      several dopamine receptor antagonists with the following rank order of potency:
      (+)-butaclamol > spiperone > raclopride > S(-)-sulpiride; but not by (-)
      butaclamol or SCH 23390. High-affinity GTPase activity was also stimulated by
      carbachol and acetylcholine through the pirenzepine-insensitive muscarinic
      receptors. Preincubation of the membranes with AS/7, a specific antiserum to Gi1
      and Gi2, appeared to attenuate dopamine-sensitive activity, suggesting that Gi1
      and/or Gi2 may be at least partially involved. These results indicate that high
      affinity GTPase activity in rat striatal membranes is activated through dopamine
      D2-like receptors and pirenzepine-insensitive muscarinic receptors, both of which
      are negatively coupled to adenylate cyclase via Gi proteins.

PMID- 7646533
TI  - Species differences in the interactions of the anticonvulsant milacemide and some
      analogues with monoamine oxidase-B.
AB  - Oxidation of the anticonvulsant drug milacemide [2-n-(pentylamino)acetamide] by
      monoamine oxidase-B (MAO-B) has been reported to be important in terminating its
      activity. Comparison of the oxidation of this compound by MAO-B preparations from
      ox and rat liver showed the former enzyme to have a significantly higher Km value
      towards this substrate. In keeping with this, the Ki values for milacemide acting
      as a competitive inhibitor of these enzymes showed it to have a lower affinity
      for ox liver MAO-B. Comparative studies on the time-dependent inhibition of the
      two enzymes also showed a lower sensitivity of that from the ox liver. Studies
      with a series of analogues involving replacement of pentylamino group of
      milacemide showed marked differences between the sensitivities of the two
      enzymes. The largest differences were shown by the compound 2(4-(3
      chlorobenzoxy)phenethylamino)acetamide which gave IC50 values of 0.051 +/- 0.008
      and 4.1 +/- 0.8 microM with the rat and ox enzymes, respectively, when activities
      were assayed without prior enzyme-inhibitor preincubation. When the enzyme and
      inhibitor were incubated for 60 min at 37 degrees before assay these values fell
      to 0.027 +/- 0.002 and 3.5 +/- 0.4 microM, respectively. These marked differences
      prompted a study of the inhibition of MAO-A and MAO-B from human liver and brain,
      mouse brain and rat brain as well as MAO-B from ox liver by milacemide and alpha
      methylmilacemide. There were no significant differences in the sensitivities of
      any of the mitochondrial MAO-A preparations studied towards these compounds.
      However, MAO-B from human brain and liver mitochondrial resembled that from ox
      liver in being less sensitive to inhibition than the rat and mouse enzymes.
      Purification of the ox liver MAO-B did not significantly affect its interactions
      with milacemide and alpha-methylmilacemide. The marked species differences
      reported here raise questions concerning the validity of rodent model systems,
      that have frequently been used for assessing the in vivo and in vitro actions of
      milacemide and its analogues, for the situation in the human.

PMID- 7646535
TI  - Protein kinase C inhibitors reduce phorbol ester-induced resistance to
      methotrexate in Chinese hamster ovary cells.
AB  - Phorbol 12-myristate 13-acetate (TPA) increases the number of colonies surviving
      methotrexate (MTX) exposure in a dose-dependent manner upon short incubation with
      Chinese hamster ovary (CHO) cells. Seventy percent of the isolated colonies
      showed increased copy number for the dihydrofolate reductase gene. EGTA prevents
      the increase in resistance triggered by TPA. Calcium ionophore A23187 and
      angiotensin II also increase this resistance, suggesting that calcium is involved
      in this process. Protein kinase C (PKC) from CHO cells is rapidly activated by
      TPA, A23187 and angiotensin II. PKC inhibitors, 1-(5-Isoquinolinylsulphonyl)-2
      methyl-piperazine (H-7), glycyrrhetinic acid, staurosporine and calphostin C
      decrease the generation of resistant colonies to MTX upon incubation with TPA.
      However, 5 nM staurosporine on its own increases resistance to MTX while having
      the ability to translocate CHO PKC. In vitro, H-7, staurosporine and calphostin C
      inhibit PKC activity translocated by TPA incubation with CHO cells. We conclude
      that PKC, the activity of which is dependent on calcium and phospholipids, is
      part of the pathway that leads to development of increased resistance to MTX.
      Thus, inhibition of PKC prevents the appearance of this resistance. Our results
      suggest the possibility of using non-toxic PKC inhibitors as resistance
      modulators in MTX chemotherapy.

PMID- 7646536
TI  - Effects of an anti-inflammatory peptide (antiflammin 2) on cell influx,
      eicosanoid biosynthesis and oedema formation by arachidonic acid and
      tetradecanoyl phorbol dermal application.
AB  - Antiflammins are synthetic peptides with sequence homology to proteins inhibitory
      for phospholipase A2 (EC 3.1.1.4). The effect of antiflammin 2 on murine
      arachidonate or 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced ear oedema has
      been studied. Topical application of arachidonic acid (AA) produced a short-lived
      oedema response with rapid onset associated with marked increases in
      prostaglandin E2 levels. TPA produced a longer-lasting oedema associated with
      marked influx of neutrophils and mononuclear cells as well as predominant
      formation of leukotriene B4 (LTB4). Topical pretreatment with indomethacin or
      dexamethasone reduced plasma leakage, oedema and prostaglandin E2 biosynthesis in
      AA-induced oedema, whereas antiflammin 2 had no effect. However, topical
      pretreatment with antiflammin 2 dose-dependently reduced plasma leakage, cell
      influx, oedema and LTB4 levels in response to TPA. These results indicate that
      the anti-inflammatory effect of antiflammins can be attributed to AA mobilization
      and/or 5 lipoxygenase inhibition but can be dissociated from an effect on
      arachidonic acid metabolism by the cyclooxygenase pathway.

PMID- 7646537
TI  - Cycad toxin-induced damage of rodent and human pancreatic beta-cells.
AB  - Environmental toxins may be risk factors for some forms of diabetes mellitus and
      neurodegenerative diseases. The medicinal and food use of seed from the cycad
      plant (Cycas spp.), which contains the genotoxin cycasin, is a proposed
      etiological factor for amyotrophic lateral sclerosis/Parkinsonism-dementia
      complex (ALS/PDC), a prototypical neurodegenerative disease found in the western
      Pacific. Patients with ALS/PDC have a very high prevalence of glucose intolerance
      and diabetes mellitus (in the range of 50-80%). We investigated whether the cycad
      plant toxin cycasin (methylazoxymethanol (MAM) beta-D-glucoside) or the aglycone
      MAM are toxic in vitro to mouse or human pancreatic islets of Langerhans. Mouse
      pancreatic islets treated for 6 days with cycasin impaired the beta-cell insulin
      response to glucose, but this effect was reversible after a further 4 days in
      culture without the toxin. When mouse islets were exposed for 24 hr to MAM/MAM
      acetate (MAMOAc; 0.1-1.0 mM), there was a dose-dependent impairment in insulin
      release and glucose metabolism, and a significant decrease in islet insulin and
      DNA content. At higher MAM/MAMOAc concentrations (1.0 mM), widespread islet cell
      destruction was observed. Glucose-induced insulin release remained impaired even
      after removal of MAM and a further culturing for 4 days without the toxin. MAM
      damages islets by two possible mechanisms: (a) nitric oxide generation, as judged
      by increased medium nitrite accumulation; and (b) DNA alkylation, as judged by
      increased levels of O6-methyldeoxyguanosine in cellular DNA. Incubation of mouse
      islets with hemin (10 or 100 microM), a nitric oxide scavenger, or nicotinamide
      (5-20 mM) protected beta-cells from a decrease in glucose oxidation by MAM. In
      separate studies, a 24 hr treatment of human beta-islet cells with MAMOAc (1.0
      mM) produced a significant decrease in both insulin content and release in
      response to glucose. In conclusion, the present data indicate that cycasin and
      its aglycone MAM impair both rodent and human beta-cell function which may lead
      to the death of pancreatic islet cells. These data suggest that a "slow toxin"
      may be a common aetiological factor for both diabetes mellitus and
      neurodegenerative disease.

PMID- 7646539
TI  - Cellular targets of 3'-azido-3'-deoxythymidine: an early (non-delayed) effect on
      oxidative phosphorylation.
AB  - Previous results demonstrated that incubation of the Friend murine
      erythroleukemic cell with 5 microM AZT for several days leads to a decrease in
      the rate of cell growth, inhibition of mtDNA replication, reduction of mtDNA per
      cell and per mitochondrion, and an increase in mitochondria per cell. As shown
      here, such treatment also leads to changes in lactate and ATP synthesis and in O2
      uptake, suggesting impairment of oxidative phosphorylation. Direct measurement of
      ATP synthesis in mitochondria isolated from AZT-treated cells confirmed this
      view. The most significant new finding in this paper, however, is that in
      addition to these delayed effects of AZT, similar but very rapidly appearing
      effects on oxidative phosphorylation were noted, with changes observed in the
      above parameters including mitochondrial proliferation. Some of these occurred as
      early as 3 hr, only 7% of the doubling time, after exposure of the cells to 5
      microM AZT, a period too short for initiation of appreciable mtDNA-mediated
      effects. Studies on isolated mitochondria provided no evidence of the identity of
      the immediate target of AZT: AZT does not act as an uncoupler or inhibitor of
      respiratory control, and previous results failed to implicate adenylate kinase.
      We have also begun to address the question of the mechanism of AZT-induced
      mitochondrial proliferation. Initial experiments showed that AZT inhibited
      synthesis of total cytosolic protein but stimulated synthesis of those proteins
      imported into mitochondria from the cytoplasm. We also report that
      aminothymidine, a catabolite of AZT in liver capable of inhibiting cell growth,
      was not generated by Friend cells.

PMID- 7646538
TI  - Metabolism of phenytoin and covalent binding of reactive intermediates in
      activated human neutrophils.
AB  - ontivation of neutrophils by phorbol-12-myristate-13-acetate (PMA) causes rapid
      production of superoxide radical (O2-), leading to the formation of additional
      reactive oxygen species, including hydrogen peroxide (H2O2), hypochlorous acid
      (HOCl), and possibly hydroxyl radical (.OH). These reactive oxygen species have
      been associated with the oxidation of some drugs. We investigated the metabolism
      of phenytoin (5,5-diphenylhydantoin) and the covalent binding of reactive
      intermediates to cellular macromolecules in activated neutrophils. In incubations
      with 100 microM phenytoin, PMA-stimulated neutrophils from six human subjects
      produced p-, m-, and o-isomers of 5-(hydroxyphenyl)-5-phenylhydantoin (HPPH) in a
      ratio of 1.0:2.1:2.8, respectively, as well as unidentified polar products.
      Analysis of cell pellets demonstrated that phenytoin was bioactivated to reactive
      intermediates that bound irreversibly to macromolecules in neutrophils.
      Glutathione, catalase, superoxide dismutase, azide, and indomethacin all
      diminished the metabolism of phenytoin and the covalent binding of its reactive
      intermediates. The iron-inactivating chelators desferrioxamine and
      diethylenetriaminepentaacetic acid had little or no effect on the metabolism of
      phenytoin by neutrophils, demonstrating that adventitious iron was not
      contributing via Fenton chemistry. In an .OH-generating system containing H2O2
      and Fe2+ chelated with ADP, phenytoin was oxidized rapidly to unidentified polar
      products and to p-, m-, and o-HPPH (ratio 1.0:1.7:1.5, respectively). Reagent
      HOCl and human myeloperoxidase (MPO), in the presence of Cl- and H2O2, both
      formed the reactive dichlorophenytoin but no HPPH. However, no chlorinated
      phenytoin was detected in activated neutrophils, possibly because of its high
      reactivity. These findings, which demonstrated that activated neutrophils
      biotransform phenytoin in vitro to hydroxylated products and reactive
      intermediates that bind irreversibly to tissue macromolecules, are consistent
      with phenytoin hydroxylation by .OH generated by a transition metal-independent
      process, chlorination by HOCl generated by MPO, and possibly cooxidation by
      neutrophil hydroperoxidases. Neutrophils activated in vivo may similarly convert
      phenytoin to reactive intermediates, which could contribute to some of the
      previously unexplained adverse effects of the drug.

PMID- 7646540
TI  - Mechanisms of resistance to N-[5-[N-(3,4-dihydro-2-methyl-4- oxoquinazolin-6
      ylmethyl)-N-methylamino]-2-thenoyl]-L-glutamic acid (ZD1694), a folate-based
      thymidylate synthase inhibitor, in the HCT-8 human ileocecal adenocarcinoma cell
      line.
AB  - N-[5-[N-(3,4-Dihydro-2-methyl-4-oxoquinazolin-6-ylmethyl)-N- methylamino]-2
      thenoyl]-L-glutamic acid (ZD1694) is a folate-based thymidylate synthase (TS; EC
      2.1.1.45) inhibitor. Metabolism to higher chain length polyglutamates is
      essential for its optimal cytotoxic effect. A ZD1694-resistant (300-fold) human
      ileocecal carcinoma cell line (HCT-8/DW2) was developed, and its mechanism of
      resistance was evaluated. TS activities in situ and TS protein levels in the HCT
      8 parental line and HCT-8/DW2 were similar (168 +/- 47 vs 137 +/- 25
      pmol/hr/10(6) cells and 2.05 +/- 0.28 vs 2.07 +/- 0.19 pmol/mg protein,
      respectively). The IC50 values of ZD1694 for TS inhibition in cell-free extracts
      were similar in both lines, but the IC50 of ZD1694 for TS inhibition in situ in
      HCT-8/DW2 cells was 27- and 268-fold higher than that in HCT-8 cells at 0 and 24
      hr, respectively, after a 2-hr drug exposure. Folylpolyglutamate synthetase
      (FPGS; EC6.3.2.17) activity was significantly lower in resistant HCT-8/DW2 cells
      as compared with parental HCT-8 cells (88 +/- 40 vs 1065 +/- 438 pmol/hr/mg
      protein when ZD1694 was used as substrate). The combined endogenous pool of
      methylenetetrahydrofolate and tetrahydrofolate in HCT-8/DW2 cells was also
      decreased. In addition, HCT-8/DW2 cells accumulated lower levels of methotrexate
      (MTX) in a 2-hr period, although the initial velocity of MTX transport was
      similar to that in parental HCT-8 cells. The lower level of FPGS activity and the
      lower level of (anti)folate accumulation in HCT-8/DW2 correlated with drug
      resistance and with the higher IC50 of ZD1694 for in situ TS inhibition. In
      addition, drug resistance was also correlated with the rapid recovery of in situ
      TS activity after drug treatment. In brief, in this highly ZD1694-resistant HCT-8
      cell line, resistance is associated with decreased FPGS activity, which, in turn,
      affects the metabolism of ZD1694 and consequently the extent and duration of in
      situ TS inhibition by the drug.

PMID- 7646541
TI  - Identification of 4-(N,N-dipropylamino)benzaldehyde as a potent, reversible
      inhibitor of mouse and human class I aldehyde dehydrogenase.
AB  - As the physiologic roles for the different classes of aldehyde dehydrogenase
      (ALDH) enzymes are elucidated, the identification of specific, reversible
      inhibitors becomes of great pharmacologic interest. Previous structure-function
      studies identified dialkylamino substituted benzaldehyde compounds as a novel
      class of reversible inhibitors of class I ALDH. To examine further structural
      requirements for inhibition, we tested a series of 4-(N,N
      dialkylamino)benzaldehyde analogs as inhibitors of propanal oxidation by mouse
      liver and human erythrocyte class I ALDH. 4-(N,N-dipropylamino)benzaldehyde
      (DPAB) was identified as the most potent, reversible inhibitor of propanal
      oxidation by class I ALDH in spectrophotometric enzyme assays. In kinetic
      studies, DPAB showed mixed-type inhibition with respect to the aldehyde
      substrates propanal, phenylacetaldehyde, benzaldehyde, and aldophosphamide. DPAB
      exhibited uncompetitive inhibition with respect to the cofactor NAD. Inhibition
      constants (Ki) for DPAB, estimated from Dixon plots, were 10 nM (propanal) and 77
      nM (phenylacetaldehyde) for mouse ALDH and 3 nM (propanal) and 70 nM
      (phenylacetaldehyde) for human ALDH. These Ki values are 100-fold lower than
      those reported for class I specific inhibitors. At low (< 1 microM) DPAB
      concentrations, inhibition of propanal and aldophosphamide oxidation was > 75%,
      whereas inhibition of benzaldehyde (32%) and phenylacetaldehyde (19%) oxidation
      was reduced markedly. These results indicate that DPAB exhibits potent,
      reversible inhibition of mouse and human class I ALDH. The degree of inhibition
      was highly dependent on the structure of the aldehyde substrate.

PMID- 7646542
TI  - Histamine, a neuromodulator of noradrenergic transmission in uterine horns from
      mice in diestrus.
AB  - The effect of histamine on [3H]norepinephrine ([3H]NE) release in uterine horns
      from mice in estrous and diestrous states was studied under two different
      experimental conditions: resting NE release and stimulus-evoked NE release. It
      was found that [3H]NE release was higher for the diestrous state under both
      resting and stimulus-evoked (100 mM K+ and electrical stimulus) conditions.
      Histamine only potentiated the stimulus-evoked [3H]NE outflow in uterine horns
      from mice in the diestrous state and from ovariectomized mice treated with
      progesterone. This effect was dose dependent and was antagonized by H1 but not by
      H2 or H3 antagonists. R-alpha-Methylhistamine, a H3 agonist, has no effect on
      stimulus-evoked [3H]NE release. According to these results, it could be concluded
      that: (a) histamine regulates the NE release from noradrenergic nerve terminals
      in uterine tissues; (b) this heterologous regulation depends on progesterone
      predominance and on terminal depolarization; and (c) presynaptic H1 receptors
      located on noradrenergic terminals could be responsible for such an effect.

PMID- 7646543
TI  - Inhibitory effects of zidovudine in erythroid progenitor cells. Reversal with a
      combination of erythropoietin and interleukin-3.
AB  - To investigate the mechanisms that may be involved in zidovudine (AZT)-induced
      hematopoietic toxicity, spleen cells isolated from phenylhydrazine-treated anemic
      mice or murine bone marrow erythroid progenitor cells were treated with AZT (1-10
      microM) for 24 hr. A concentration-dependent inhibition of the binding of 125I
      labeled erythropoietin (Epo) was observed, suggesting down-regulation of Epo
      receptors. To determine if this effect is due to modulation of the levels of Epo
      receptor mRNA and to assess the effect of AZT on the expression of
      protooncogenes, mRNA levels were monitored by the slot blot hybridization
      technique. AZT caused a concentration-dependent inhibition in the levels of the
      mRNA of Epo receptors and c-fos, whereas the level of c-myc mRNA was unaffected.
      AZT also inhibited protein kinase C (PKC) activity in a concentration- and time
      dependent manner, causing 50% inhibition at 10 microM within 3 hr. Simultaneous
      addition of Epo or interleukin-3 (IL-3) partially reversed the inhibitory effects
      of AZT on the levels of the mRNAs and on PKC activity; however, a combination of
      Epo and IL-3 was significantly more effective. These studies demonstrate that (i)
      AZT-induced down-regulation of Epo receptors and c-fos expression coupled with
      inhibition of Epo receptor-mediated signal transduction through PKC are
      significant contributory factors to AZT-induced erythroid toxicity, and (ii)
      these inhibitory effects can be overcome by treatment with a combination of Epo
      and IL-3.

PMID- 7646544
TI  - Ontogenesis of rat liver microsomal glutathione transferase.
AB  - The ontogenesis of rat liver microsomal glutathione transferase was investigated
      by activity measurements and immunochemical methods. The activity rises from a
      very low level (3% of adults) at day 8 pre-partum to adult levels at days 50-150.
      Increases are associated with the neonatal and late-suckling clusters.
      Interestingly the capacity to become activated by N-ethylmaleimide is much lower
      in females early and late in life (days 35-100 and 300-550). After the initial
      increases (from 10% of adult levels at day 8 pre-partum), protein levels
      determined immunochemically remain constant throughout life with no apparent sex
      differences. The developmental pattern of microsomal glutathione transferase
      resembles those of other drug-metabolizing enzymes indicating that the function
      of the enzyme is required in adult life.

PMID- 7646545
TI  - Effects of two distamycin-ellipticine hybrid molecules on topoisomerase I and II
      mediated DNA cleavage: relation to cytotoxicity.
AB  - Two distamycin-ellipticine conjugates were examined for their ability to modulate
      topoisomerase I and topoisomerase II-DNA cleavable complex formation in vitro.
      Hybrid molecules Distel (1+) and Distel (2+) both contain a DNA-intercalating
      chromophore and a tris-pyrrole element capable of binding within the minor groove
      of DNA. The two drugs differ only in the nature of the side chain attached to the
      distamycin moiety. The monocationic hybrid Distel (1+) is a dual topoisomerase I
      and II inhibitor with characteristics differing from those of the parent
      compounds distamycin and ellipticine. By contrast, the biscationic hybrid Distel
      (2+) exerts no significant effects on either topoisomerase I or II. The cytotoxic
      properties of the two drugs towards P388 leukaemic cells sensitive and resistant
      to camptothecin correlate with topoisomerase inhibitory properties but not with
      DNA-binding properties.

PMID- 7646546
TI  - Effect of stereochemistry on the oxidative metabolism of the cyclophosphamide
      metabolite aldophosphamide.
AB  - 31P NMR and cell perfusion techniques were used to investigate the conversion of
      the individual enantiomers of aldophosphamide (AP) to carboxyphosphamide (CBP) as
      catalyzed by aldehyde dehydrogenase in human erythroleukemia K562 cells. R- and S
      cyclophosphamides (CPs) were treated with ozone and hydrogen peroxide to yield Rp
      and Sp-cis-4-hydroperoxycyclophosphamides (Rp- and Sp-cis-4-HO2-CP); reduction
      of each hydroperoxide gave the corresponding enantiomer of AP [along with its
      tautomer 4-hydroxycyclophosphamide (4-HO-CP)]. In separate experiments, K562
      cells embedded in agarose gel threads were perfused at pH 7.4, 21 +/- 1 degrees,
      with solutions of 1.4 mM Rp- and Sp-4-HO-CP/AP, both with and without added mesna
      (an acrolein scavenger). A comparison of the 31P NMR spectral data derived from
      the experiments revealed little statistical difference (+/- 10-20% error limits)
      in the normalized intensities of the CBP peaks arising from the individual AP
      enantiomers [with added mesna, the ratio Rp-CBP:Sp-CBP was 1.00:1.24 +/- 0.13
      (average deviation); without mesna, the same ratio was 1.00:1.35]. Using
      conventional methods for evaluating the in vitro drug toxicities, CP-resistant
      L1210 cells were treated in separate experiments with Rp- and Sp-cis-4-HO2-CP;
      there were no significant differences between the toxicities exhibited by the
      stereoisomers.

PMID- 7646547
TI  - Neurotransporters: regulation, involvement in neurotoxicity, and the usefulness
      of antisense nucleic acids.

PMID- 7646548
TI  - Influx of daunorubicin in multidrug resistant Ehrlich ascites tumour cells:
      correlation to expression of P-glycoprotein and efflux. Influence of verapamil.
AB  - Classic multidrug resistance is characterized by a decrease in the intracellular
      concentration of drugs in resistant cells as compared to sensitive cells. This is
      correlated with the presence of P-glycoprotein in the membrane. P-glycoprotein is
      responsible for an active efflux of drug. In this study we investigated the
      correlation between P-glycoprotein and influx of daunorubicin. Four Ehrlich
      ascites tumour cell lines selected in vivo for resistance to daunorubicin were
      investigated. The sublines EHR2/0.1, EHR2/0.2, passage no. 12 of EHR2/0.8,
      EHR2/0.4, and passage no. 72 of EHR2/0.8 were 6-, 6-, 5-, 33-, and 35-fold
      resistant to daunorubicin, respectively. All sublines overexpressed P
      glycoprotein as determined with Western blot. Influx was measured over 40 sec. In
      glucose-enriched medium influx was significantly decreased in all but one of the
      resistant sublines. A correlation between P-glycoprotein, degrees of resistance,
      and influx was demonstrated in four sublines. Comparing influx experiments with
      efflux experiments (Nielsen et al., Biochem Pharmacol 1994, 47, 2125-2135) we
      found a linear relationship between influx and efflux in the resistant sublines
      (r = 0.97). Verapamil (5.5 microM, 11.0 microM) increased influx significantly in
      all resistant sublines, whereas the drug had no effect on sensitive cells.
      Verapamil (3.3 microM) increased influx in the EHR2/0.8 (passage no. 72) subline
      to the level of sensitive cells. Comparing this result with efflux experiments,
      verapamil was found to increase influx preferentially. Depletion of energy
      (medium without glucose including Na(+)-azide) increased influx in all resistant
      sublines. In EHR2/0.4 and EHR2/0.8 (passage no. 72) the influx, however, was
      still significantly decreased after depletion of energy. In these cells further
      addition of verapamil increased influx to the level of EHR2. These data were
      consistent with the hypothesis that P-glycoprotein effluxes drug directly from
      the plasma membrane.

PMID- 7646549
TI  - Reversal of multidrug resistance by verapamil analogues.
AB  - The basic distinguishing feature of multidrug resistant (MDR) cells is a decrease
      in steady-state drug levels as compared to drug-sensitive controls. It is well
      known that verapamil increases the sensitivity of MDR cells to drugs, thus
      reverting drug resistance. A limiting factor for its clinical use is the
      pronounced cardiovascular effects of the calcium channel antagonist which occur
      at the high plasma concentrations required to block P-glycoprotein transport
      efficiently. From a clinical point of view, it is important to find verapamil
      derivatives with low calcium channel blocking activity and high reverting
      activity. This was the aim of the present study. In this context we have
      investigated the ability of 20 verapamil analogues with restricted molecular
      flexibility to increase cellular accumulation of anticancer drugs and overcome
      resistance, and their inotropic, chronotropic, and slow calcium channel
      antagonistic activity. In this study an anthracycline derivative 4'-O
      tetrahydropyranyl adriamycin, and an erythroleukaemia K562 cell line were used.
      Three of the 20 derivatives checked were completely devoid of calcium channel
      blocking activity while exhibiting MDR reverting ability comparable to that of
      verapamil. These derivatives could be useful for the treatment of MDR in cancer
      patients and for the design and development of other verapamil derivatives.

PMID- 7646550
TI  - Cross-resistance studies on two K562 sublines resistant to
      diaziridinylbenzoquinones.
AB  - Two resistant K562 sublines have been developed by treatment with AZQ (2,5
      bis(carboethoxyamino)-3,6-diaziridinyl-1,4-benzoquinone) and BZQ (2,5-bis(2
      hydroxyethylamino)-3,6-diaziridinyl-1,4-benzoquinone). The ID50 values of for AZQ
      on K562, the AZQ-resistant sublines (AZQR) and the BZQ-resistant sublines (BZQR)
      were 0.063, 1.47 and 0.244 microM, respectively. The relative ID50 values for BZQ
      on the same cell lines were 0.2, 0.67 and 0.83 microM, respectively. Although it
      is generally believed that these two quinones function by different mechanisms,
      the two sublines have similar decreased levels of cytochrome P-450 reductase and
      DT-diaphorase and increased levels of glutathione and superoxide dismutase,
      compared to the parent cell line. The sublines are also cross-resistant to
      adriamycin, mitozolamide, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and
      mitomycin C. This work indicates the potential multifactorial mechanisms by which
      drug resistance can be induced in cell lines in the absence of conventional 'P'
      glycoprotein multidrug resistance.

PMID- 7646551
TI  - Lipocortin-1 and the control of arachidonic acid release in cell signalling.
      Glucocorticoids (changed from glucorticoids) inhibit G protein-dependent
      activation of cPLA2 activity.
AB  - In pre-labelled A549 cells epidermal growth factor (EGF) (10 nM) stimulates the
      release of [5,6,8,9,11,12,14,15-3H(N)]-arachidonic acid (3H-AA) by approximately
      70%. Increasing Ca2+i with thapsigargin (50 nM) stimulates 3H-AA release by
      approximately 120%. However, the combined use of these two agents results in a
      synergistic stimulation of 3H-AA release by over 700%. The EGF stimulated release
      is sensitive to pertussis toxin (10 ng/mL) and guanosine 5'-O-(2-thiodiphosphate)
      suggesting a G protein-mediated event. This is supported by the fact that the G
      protein activators AlF-4 and guanosine 5'-O-(2-thiotriphosphate) both stimulate
      3H-AA release. The stimulation of 3H-AA release by both EGF or direct G protein
      activation is completely blocked following pre-treatment for 3 hr with 1 nM
      dexamethasone. This effect is reversed with a neutralizing antibody to lipocortin
      1 (1 microgram/mL) suggesting that this protein mediates the inhibitory effects
      of glucocorticoids on agonist activated 3H-AA release. Thapsigargin stimulation
      of 3H-AA release is insensitive to dexamethasone treatment. A peptide fragment
      from the N-terminus of lipocortin-1-Lc13-25 (20-200 micrograms/mL) mimics the
      effect of glucocorticoid in suppressing both EGF and G protein activated 3H-AA
      release. A peptide with Me-Tyr substituting Tyr21 is much reduced in activity
      suggesting that the presence of this residue is essential. As peptide Lc13-25 is
      not derived from the Ca2+/phospholipid binding domain of the native protein then
      sequestration of phospholipid substrate for PLA2 remains an unlikely mechanism of
      action for this peptide.

PMID- 7646552
TI  - Expression of multidrug resistance in response to differentiation in the K562
      human leukaemia cell line.
AB  - With the increasing use of inducers of cellular differentiation in the treatment
      of leukaemia, it is essential to understand the relationship between
      differentiation and the expression of the multidrug resistance. Using the K562
      human leukaemia cell line and its multidrug resistant subline K562/E15B,
      differentiation was examined along two different pathways, megakaryocyte in
      response to treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA), and
      erythroid in response to treatment with sodium butyrate, in the same cell line. P
      glycoprotein expression was increased in the multidrug resistant K562/E15B
      subline, but not induced in the parental K562 cell line. However, both treatments
      conferred a different phenotype on the drug resistant subline. TPA treatment
      caused an increase in P-glycoprotein, increased drug resistance and decreased
      rhodamine-123 accumulation which was verapamil sensitive, demonstrating that TPA
      induced a fully functional P-glycoprotein. However, sodium butyrate treatment
      caused an increase in P-glycoprotein without increased drug resistance or without
      decreased rhodamine-123 accumulation suggesting that the P-glycoprotein induced
      by sodium butyrate was nonfunctional. These results stress the importance of
      examining not only the expression of P-glycoprotein in cells, but also the
      function of the P-glycoprotein induced.

PMID- 7646554
TI  - Degradation of 2-(3-aminopropylamino)-ethanethiol (WR-1065) by Cu-dependent amine
      oxidases and influence on glutathione status of Chinese hamster ovary cells.
AB  - The radioprotective drug 2-(3-aminopropylamino)ethanethiol (WR-1065) can be
      degraded when incubated in cell culture medium in vitro. The degradation reaction
      consumes oxygen and results from the action of Cu-dependent amine oxidases
      present in the serum content of the medium. Analysis of the degradation products
      of WR-1065 demonstrates the formation of cysteamine, acrolein and H2O2. WR-2721,
      the inactive prodrug of WR-1065, is not a substrate for these enzymes.
      Extracellular degradation of WR-1065 by Cu-dependent amine oxidases leads to an
      intracellular depletion of glutathione (GSH) in Chinese hamster ovary (CHO) cells
      and to reduction of clonogenic cell survival. Addition of aminoguanidine, an
      inhibitor of Cu-dependent amine oxidases, protects CHO cells from the toxic
      effects of WR-1065 and under these conditions an increase of intracellular GSH
      levels occurs. These data demonstrate that WR-1065 can be degraded to toxic
      compounds by the presence of Cu-dependent amine oxidases which might have further
      implications for the clinical use of WR-2721.

PMID- 7646553
TI  - Inhibition of protein synthesis induced by adenine nucleotides requires their
      metabolism into adenosine.
AB  - Adenine nucleotides and adenosine inhibit the incorporation of radiolabelled
      leucine into proteins of isolated hepatocytes. Impairment occurred with
      nucleotides which can be converted into 9-beta-D-ribofuranosyladenine (adenosine)
      but was not observed after treatment with adenine or AMPCPP (the alpha, beta
      methylene analogue of ATP). Metabolism into adenosine was further suggested by
      the increase in cellular ATP levels following treatment of hepatocytes with ATP,
      adenosine or AMPPCP (the beta, gamma-methylene ATP analogue) while AMPCPP was
      without any significant effect. The inhibition of protein synthesis caused by
      adenosine was not due to a lytic effect nor to a general disturbance in hepatic
      functions and was reversed when the cells were washed and transferred to a
      nucleoside-free medium. This impairment, however, was not coupled to the
      activation of adenylate cyclase, as preincubation of hepatocytes with P1
      purinoceptor antagonists failed to prevent protein synthesis inhibition. In
      contrast, L-homocysteine enhanced the inhibitory effect of adenosine on the
      incorporation of radiolabelled leucine into proteins. Our results thus suggest
      that the inhibition of protein synthesis caused by adenine nucleotides requires
      their conversion into adenosine. They also indicate that the inhibitory effect of
      adenosine does not involve a receptor-mediated effect but may be related to an
      increase in S-adenosylhomocysteine content and a subsequent low level of
      macromolecule methylation.

PMID- 7646555
TI  - The alterations in the energy linked properties induced in rat liver mitochondria
      by acetylsalicylate are prevented by cyclosporin A or Mg2+.
AB  - The alterations in rat liver mitochondria induced by acetylsalicylate in the
      presence of low concentrations of Ca2+ (large amplitude swelling, permeability to
      14C]sucrose, collapse of transmembrane potential and effluxes of endogenous Mg2+
      and accumulated Ca2+) were fully prevented by either cyclosporin A or Mg2+.
      Cyclosporin A and Mg2+ were also capable of restoring transmembrane potential
      upon its decrease induced by acetylsalicylate. The loss of endogenous Mg2+ was
      the primary effect promoted by acetylsalicylate; the other noxious effects
      followed. These results indicate that Mg2+ are fundamental components of the
      mitochondrial permeability barrier and that their loss might be responsible for
      the membrane transition induced by acetylsalicylate.

PMID- 7646556
TI  - Differential regulation of soluble epoxide hydrolase by clofibrate and sexual
      hormones in the liver and kidneys of mice.
AB  - Soluble epoxide hydrolase (sEH) activity was measured in the liver and kidneys of
      male, female, and castrated male mice in order to evaluate sex- and tissue
      specific differences in enzyme expression. sEH activity was found to be higher in
      liver than in kidneys. Activity increased with age in the liver of females, males
      and castrated males, but only in males did activity in the kidneys increase.
      There was greater activity in both the liver and kidneys of adult males than
      females. This sexual dimorphism was more pronounced in the kidneys (283% higher)
      than in the liver (55% higher). Castration of males led to a decrease in activity
      in both organs, but it had a greater effect on renal activity (67% decrease) than
      on hepatic activity (27% decrease). Treatment of castrated mice with testosterone
      led to an increase in sEH activity of 400% in kidneys and 49% in liver compared
      with surgical controls. These results suggest differential regulation of sEH by
      testosterone in kidneys and liver. Ovariectomized female mice had renal and
      hepatic activities approximately 30% greater than control females. Feeding mice
      with the hypolipidemic drug clofibrate produced stronger induction of sEH in
      liver than in kidneys. Testosterone treatment, however, caused greater induction
      in kidneys than in liver of females and castrated males and had no effect in
      either kidneys or liver in males. When given together, the effects of these two
      compounds appeared to be additive in both liver and kidneys. Results from western
      blot showed that the increase in sEH enzyme activity in kidneys is correlated
      with an increase in sEH protein. These results suggest that clofibrate and
      testosterone independently regulate sEH activity in vivo, and that kidneys and
      liver respond differently to clofibrate and testosterone.

PMID- 7646557
TI  - Gender-related differences in the amount and functional state of rat liver UDP
      glucuronosyltransferase.
AB  - The basis for gender-dependent differences in rates of glucuronidation of
      xenobiotics is uncertain. To clarify this issue, the glucuronidation of p
      nitrophenol was compared in liver microsomes from adult male and female rats. The
      activity of native UDP-glucuronosyltransferase was 47% higher in microsomes from
      male than from female rats. Immunoblotting of microsomal protein with anti-UDP
      glucuronosyltransferase antiserum revealed 66% more immunoreactive protein in
      male microsomes. A kinetic method for measuring glucuronidating enzyme content
      confirmed the result of the immunoblot. Responses of UDP-glucuronosyltransferase
      to activation by palmitoyllysophosphatidylcholine or high pressure indicated that
      the activity of the enzyme was more latent in male than in female microsomes.
      Differences in enzyme latency could be due to differences in membrane structure.
      A comparison of microsomal fatty acid composition revealed significantly higher
      levels of oleic and linoleic acids and lower levels of stearic and
      docosahexaenoic acids in male than in female microsomes. The phospholipid
      composition, ratio of cholesterol:phospholipid, and membrane fluidity were
      similar in male and female microsomes. These results indicate that gender
      dependent differences in UDP-glucuronosyltransferase activity are due to
      differences in both the amount and functional state of the enzyme.

PMID- 7646558
TI  - Remission of liver fibrosis by interferon-alpha 2b.
AB  - Fibrosis is a dynamic process associated with the continuous deposition and
      resorption of connective tissue, mainly collagen. Therapeutic strategies are
      emerging by which this dynamic process can be modulated. Since interferons are
      known to inhibit collagen production, the aim of this study was to investigate if
      the administration of interferon-alpha 2b (IFN-alpha) can restore the normal
      hepatic content of collagen in rats with established fibrosis. Fibrosis was
      induced by prolonged bile duct ligation. IFN-alpha (100,000 IU/rat/day; s.c.) was
      administered to fibrotic rats for 15 days. Bile duct ligation increased liver
      collagen content 6-fold. In addition, serum and liver markers of hepatic injury
      increased significantly; liver histology showed an increase in collagen
      deposition, and the normal architecture was lost, with large zones of necrosis
      being observed frequently. IFN-alpha administration reversed to normal the values
      of all the biochemical markers measured and restored the normal architecture of
      the liver. Our results demonstrated that IFN-alpha is useful in reversing
      fibrosis and liver damage induced by biliary obstruction in the rat. However,
      further investigations are required to evaluate the therapeutic relevance of
      interferons on non-viral fibrosis and cholestasis.

PMID- 7646559
TI  - Isoflurane and cytochrome b5 stimulation of 2-chloro-1,1-difluoroethene
      metabolism by reconstituted rat CYP2B1 and CYP2C6.
AB  - Isoflurane stimulates the metabolism of 2-chloro-1,1-difluoroethene (CDE) in
      liver microsomes from phenobarbital-treated rats or rabbits. The P450 isozymes
      involved and the mechanism by which such stimulation occurs have not been
      clarified. The present study examined the effects of isoflurane and cytochrome b5
      on CDE metabolism in reconstituted systems containing purified rat CYP2B1 or
      CYP2C6. Under similar incubation conditions, CYP2B1 defluorinated CDE at
      approximately five times the rate of CYP2C6. Isoflurane was a potent stimulator
      of CDE metabolism, increasing it nearly 5-fold when catalyzed by CYP2B1, but only
      2-fold when catalyzed by CYP2C6. Isoflurane had no stimulatory effect on
      benzphetamine metabolism by CYP2B1 or CYP2C6. Cytochrome b5 was not required for
      isoflurane-facilitated CDE metabolism; however, the addition of cytochrome b5 to
      CYP2B1 increased CDE metabolism 71 and 44%, in the absence and presence of
      isoflurane, respectively. In reconstituted CYP2B1, isoflurane generated a type I
      difference spectrum of approximately twice the magnitude of CDE and stimulated
      NADPH consumption more so than CDE. The same quantity of NADPH was consumed when
      CDE was present with isoflurane as compared with isoflurane alone. These data
      support the hypothesis that isoflurane stimulates CDE metabolism by a mechanism
      involving increased P450 reduction via direct isoflurane interaction with P450.

PMID- 7646560
TI  - Azalanstat (RS-21607), a lanosterol 14 alpha-demethylase inhibitor with
      cholesterol-lowering activity.
AB  - Agents that inhibit hepatic cholesterol biosynthesis reduce circulating
      cholesterol levels in experimental animals and humans, and may be of
      pharmacological importance in the prevention of atherosclerosis. Azalanstat (RS
      21607), a synthetic imidazole, has been shown to inhibit cholesterol synthesis in
      HepG2 cells, human fibroblasts, hamster hepatocytes and hamster liver, by
      inhibiting the cytochrome P450 enzyme lanosterol 14 alpha-demethylase. When
      administered orally to hamsters fed regular chow, RS-21607 (50 mg/kg/day) lowered
      serum cholesterol in a dose-dependent manner (ED50 = 62 mg/kg) in a period of 1
      week. It preferentially lowered low density lipoprotein (LDL) cholesterol and apo
      B relative to high density lipoprotein (HDL) cholesterol and apo A-1. It also
      lowered plasma cholesterol levels in hamsters fed a high saturated fat and
      cholesterol diet. RS-21607 inhibited hepatic microsomal hydroxymethylglutaryl-CoA
      (HMG-CoA) reductase activity in hamsters in a dose-dependent manner (ED50 = 31
      mg/kg), and this was highly correlated with serum cholesterol lowering (r =
      0.97). Cholesterol lowering by azalanstat and cholestyramine was additive, and
      the increase in HMG-CoA reductase brought about by cholestyramine was attenuated
      significantly by azalanstat. In vitro studies with HepG2 cells indicated that
      this modulation of reductase activity was indirect, occurring at a post
      transcriptional step, and it is proposed that a regulatory oxysterol derived from
      dihydrolanosterol (or lanosterol) may be responsible for this regulation.
      Azalanstat does not appear to lower circulating cholesterol in the hamster by up
      regulation of the hepatic LDL receptor, suggesting that other mechanisms are
      involved. Orally administered azalanstat (50-75 mg/kg) stimulated hepatic
      microsomal cholesterol 7 alpha-hydroxylase activity by 50-400% in hamsters, and
      it is postulated that this may result from modified cholesterol absorption and
      bile acid synthesis.

PMID- 7646561
TI  - In vivo stability, disposition and metabolism of a "hybrid" oligonucleotide
      phosphorothioate in rats.
AB  - Oligodeoxynucleotide phosphorothioates containing segments of 2'-O
      methyloligoribonucleotide phosphorothioates at both 3'- and 5'-ends (hybrid
      oligonucleotide) have been shown to be potent antisense agents. In the present
      study, in vivo biostability, disposition, and excretion of a 25-mer hybrid
      oligonucleotide were determined in rats after i.v. bolus administration of the
      35S-labeled oligonucleotide at a dose of 30 mg/kg. The plasma disappearance curve
      for the hybrid oligonucleotide could be described by a two-compartmental model,
      with half-lives of 0.34 and 52.02 hr, respectively. The majority of the
      radioactivity in plasma was associated with the intact hybrid oligonucleotide.
      Urinary excretion represented the major pathway of elimination, with 21.98 +/-
      3.21% (mean +/- SD) of the administered dose excreted within 24 hr and 38.13 +/-
      2.99% over 240 hr post-dosing. The majority of the radioactivity in urine was
      associated with the degradative products with lower molecular weights, but the
      intact form was also detected by HPLC analysis. Fecal excretion was a minor
      pathway of elimination with 2.34 +/- 0.13% of the administered dose excreted over
      24 hr and 6.74 +/- 0.40% over 240 hr post-dosing. A wide tissue distribution of
      hybrid oligonucleotide was observed based on radioactivity levels, and analysis
      by HPLC showed that the majority of the radioactivity in tissues was associated
      with the intact hybrid oligonucleotide. Further analyses of the experimental data
      provided a comprehensive pharmacokinetic analysis of hybrid oligonucleotide in
      each tissue. Compared with a previously examined oligodeoxynucleotide
      phosphorothioate (GEM 91) that has a similar nucleotide sequence, the hybrid
      oligonucleotide had a shorter distribution half-life and a longer elimination
      half-life, based on the quantitation of radioactivity in plasma. Although it had
      a similar tissue distribution pattern compared with other oligonucleotide
      phosphorothioates such as GEM 91, the hybrid oligonucleotide was more stable in
      vivo, which may be important in the development of antisense oligonucleotides as
      therapeutic agents.

PMID- 7646562
TI  - Glucuronidation in the Caco-2 human intestinal cell line: induction of UDP
      glucuronosyltransferase 1*6.
AB  - The ability of the differentiated human intestinal cell line, Caco-2, to
      glucuronidate various endobiotic and xenobiotic molecules was investigated.
      Glucuronidation of hydroxylated or carboxylic acid compounds such as 1-naphthol,
      thymol, androsterone, estriol, hyodeoxycholic acid, lithocholic acid,
      chloramphenicol, paracetamol and morphine could be determined in microsomal
      fractions of Caco-2 cells. The activity toward 1-naphthol was the highest
      glucuronidation activity measured in Caco-2 cells. This activity was specifically
      increased four-fold upon addition of beta-naphthoflavone into culture medium but
      not by rifampicine or clofibrate and was related to a biosynthesis of UDP
      glucuronosyltransferase 1*6 (UGT1*6). alpha-Naphthoflavone did not affect the
      inducing property of beta-naphthoflavone. 7-Ethoxyresorufin-O-dealkylation
      activity, supported by cytochrome P4501A1, was induced more than 1000-times in
      Caco-2 cells by beta-naphthoflavone treatment, and this effect was partially
      abolished by alpha-naphthoflavone treatment. The results suggest that several
      isoforms, including UGT1*6, are expressed in Caco-2 cells.

PMID- 7646563
TI  - Effects of L-carnitine on the renal tubular transport of cephaloridine.
AB  - It has been demonstrated recently that cephaloridine (Cld) inhibits the tubular
      reabsorption of filtered carnitine (Carn) in the rabbit kidney. This interaction
      has suggested that the limited net cell-to-luminal fluid movement of Cld
      following its secretory transport across the antiluminal membrane might result
      from a balance of active Cld reabsorption by a Carn carrier at the brush border
      approximately equal to its secretion into the tubular fluid, rather than the
      previously proposed luminal membrane block. Studies were done to determine the
      effects of L-Carn, 750 mg/kg, i.v. on the tubular secretion and cortical
      concentrations of Cld, infused i.v. at a dose of 28 mg/kg (Carn:Cld molar ratio =
      70:1). The fractional excretions of Cld during three consecutive periods of 10
      min each, one before and two following the bolus infusion of Carn, were (means +/
      SEM): 1.18 +/- 0.14, 1.20 +/- 0.14, and 1.16 +/- 0.11, respectively (N = 6 each;
      differences NS). Cortex-to-serum concentration ratios of Cld in control and Carn
      treated rabbits were 10.43 +/- 0.32 and 10.16 +/- 0.86, respectively (NS). The
      data provide evidence against the reabsorptive transport of Cld by a Carn
      carrier, and do not support a model of balanced secretion and reabsorption as the
      cause of limited clearance despite significant secretory transport of Cld into
      the tubular cell.

PMID- 7646564
TI  - In vitro-in vivo correlations of human (S)-nicotine metabolism.
AB  - The profile of (S)-nicotine metabolism in human liver microsomes was examined at
      concentrations approaching in vivo conditions (10 microM). At such
      concentrations, no (S)-nicotine N-1'-oxygenation was seen, and thus C-oxidation
      to the (S)-nicotine delta 1',5'-iminium ion was the sole product observed in the
      metabolic profile in the presence of the human liver microsomes. For simplicity
      of analysis, the (S)-nicotine delta 1',5'-iminium ion formed was converted to (S)
      cotinine in the presence of exogenously added aldehyde oxidase. To explain the
      lack of (S)-nicotine N-1'-oxygenation at low (S)-nicotine concentrations,
      inhibition of flavin-containing monooxygenase (FMO) activity by (S)-cotinine was
      examined. Although (S)-cotinine was observed to inhibit pig FMO1 (Ki = 675
      microM), partially purified cDNA-expressed adult human liver FMO3 was not
      inhibited by (S)-cotinine. We therefore concluded that the kinetic properties of
      the nicotine N'- and C-oxidases were responsible for the metabolic product
      profile observed. Kinetic constants were determined for individual human liver
      microsomal preparations from low (10 microM) and high (500 microM) (S)-nicotine
      concentrations by monitoring (S)-cotinine formation with HPLC. The mean Kmapp and
      Vmax for formation of (S)-cotinine by the microsomes examined were 39.6 microM
      and 444.3 pmol.min-1.(mg protein)-1, respectively. The formation of (S)-cotinine
      was strongly dependent on the previous drug administration history of each
      subject, and among the highest rates for (S)-cotinine formation were those of the
      barbiturate-pretreated subjects. The rate of (S)-cotinine formation at low (10
      microM) concentration correlated well with immunoreactivity for cytochrome P450
      2A6 (r = 0.89). In vitro-in vivo correlation of the results suggests that the low
      amount of (S)-nicotine N-1'-oxygenation and the large amount of (S)-cotinine
      formed in human smokers (i.e. 4 and 30% of a typical dose, respectively) are
      determined primarily by the kinetic properties of the human monooxygenase enzyme
      systems. However, additional non-hepatic monooxygenase(s) contributes to (S)
      nicotine metabolism.

PMID- 7646565
TI  - Absorption, tissue distribution and in vivo stability in rats of a hybrid
      antisense oligonucleotide following oral administration.
AB  - In vivo stability and oral bioavailability of an oligodeoxynucleotide
      phosphorothioate containing segments of 2'-O-methyloligoribonucleotide
      phosphorothioates at both the 3'- and 5'-ends (hybrid oligonucleotide) were
      studied. A 25-mer 35S-labeled hybrid oligonucleotide was administered to rats by
      gavage at a dose of 50 mg/kg body weight. HPLC analysis revealed that this hybrid
      oligonucleotide was stable in the gastrointestinal tract for up to 6 hr following
      oral administration. Radioactivity associated with the hybrid oligonucleotide was
      detectable in portal venous plasma, systemic plasma, various tissues, and urine.
      Intact hybrid oligonucleotide was detected, by HPLC analysis, in portal venous
      plasma, systemic plasma, and various tissues. The majority of the radioactivity
      in urine was associated with degradative products with lower molecular weights,
      but the intact form was also detected. In summary, the hybrid oligonucleotide was
      absorbed intact through the gastrointestinal tract, indicating the possibility of
      oral administration of oligonucleotides, a finding that may be important in the
      development of antisense oligonucleotides as therapeutic agents.

PMID- 7646566
TI  - Effect of physostigmine on cholinesterase activity in different parts of rat
      brain.
AB  - Inhibition of acetylcholinesterase (AChE) in the whole brain, cerebellum, pons,
      frontal cortex, basal ganglia and medulla oblongata of rat brain by physostigmine
      (CAS 57-47-6) in vitro was studied. Constants characterizing this inhibition
      namely: binding constant (KI) and bimolecular rate constant (K'2) were
      determined. The highest values of K'2 were obtained in the cases of pons and
      medulla oblongata, the parts responsible for the respiratory and vital centers.
      The difference in the inhibition of AChE in the different parts of the brain
      could be due to the difference in the grey and white matters contents in these
      parts.

PMID- 7646567
TI  - Synthesis of N1-substituted benzamidines. Effects on blood coagulation, platelet
      aggregation and antiarrhythmic activity.
AB  - A series of N1-substituted-4-alkoxybenzamidines was synthesized and tested in
      vitro for their inhibitory effects on blood coagulation and agonist induced
      platelet aggregation. The antiarrhythmic activity against chloroform-induced
      arrhythmias in mice was also evaluated. The biological activity of the title
      compounds is reported in comparison with that of procainamide; among the new
      products described, IVi and IVe were found to have the most potent anti-platelet
      and antiarrhythmic activity, respectively. The structure-activity relationships
      are discussed.

PMID- 7646568
TI  - Pharmacokinetics and plasma protein binding of the new potent class III
      antiarrhythmic agent 3-[4-(1H-imidazol-1-yl)benzoyl]-7-isopropyl-3, 7
      diazabicyclo[3.3.1]nonane dihydroperchlorate.
AB  - GLG-V-13 (3-[4-(1H-imidazol-1-yl)benzoyl]-7-isopropyl-3,7-diazabicyclo [3.3.1]
      nonane dihydroperchlorate, CAS 155029-33-7) has been shown to be a potent class
      III antiarrhythmic agent. The oral and intravenous pharmacokinetics and plasma
      protein binding of GLG-V-13 in dogs and in rabbits have now been investigated.
      Plasma GLG-V-13 concentration-time profiles, following an i.v. bolus dose of 6
      mg/kg, were fitted to a 2-compartment model. The volume of distribution at steady
      state (Vd(ss)), the total systemic (ClB), and the elimination half-life (t1/2
      beta) were 4.441 l/kg, 1.113 l/h/kg, and 2.485 h in dogs and 3.723 l/kg, 1.548
      l/h/kg, and 1.401 h in rabbits. Following i.v. dosing, approximately 9.38% of the
      parent compound was excreted in dogs urine (0-72 h). Changes in plasma GLG-V-13
      concentrations, after oral administration of GLG-V-13 (6 mg/kg), were best
      described by the 1-compartment pharmacokinetic model. The tmax and Cmax were 1.69
      h, 0.54 mg/l in dogs and 1.44 h, 0.35 mg/l in rabbits. On oral administration,
      GLG-V-13 was moderately eliminated (t1/2kel' 1.867 h-1 in dogs and 3.961 h-1 in
      rabbits, respectively). Oral bioavailability was estimated to be 53.2% +/- 11.3%
      in dogs and 66.7% +/- 7.7% in rabbits. About 8.74% of the oral dose (6 mg/kg) was
      excreted via the dog urine (0-72 h). In vitro binding of GLG-V-13 to dog plasma
      protein was 29.4 +/- 9.90% (from 0.5 to 4 mg/l). Ex vivo binding of GLG-V-13 to
      dog plasma protein was 10.4 +/- 7.20%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7646569
TI  - Cardiotoxicity of parenterally administered iron complexes.
AB  - The role of cell calcium overload in the cardiotoxicity of low molecular weight
      iron complexes has been studied using 45Ca(2+)-uptake determinations in mice
      intraperitoneally injected with ferric lactate and ferric-ATP complex. Heart
      tissue shows a very high increase of 45Ca(2+)-uptake which appears to corroborate
      the hypothesis of cardiotoxicity by calcium overload. ATP seems to play a role in
      the degree of iron complex efficiency as cell calcium homeostasis modifier.

PMID- 7646570
TI  - Diurnal oscillations in the serum and salivary levels of quinidine.
AB  - The pharmacokinetics of quinidine in healthy subjects was studied through serum
      and salivary compartments by orally administering 250 mg of quinidine sulphate
      (CAS 50-54-4) either at 10:00 or 22:00 h. Quinidine concentrations in the
      biological samples were determined fluorimetrically. None of the pharmacokinetic
      parameters obtained from serum levels showed any significant time dependent
      changes. However, prolongation in tmax and lowering of Ka and t1/2 was noticed
      after nocturnal drug administration when the parameters were computed from
      salivary levels. Also, significant (p < 0.05) lowering of saliva/serum (SL/SR)
      ratios was observed after 22:00 h drug dosing. Temporal alterations in quinidine
      secretion into saliva could be the reason for the above changes. Alteration of
      salivary quinidine levels in turn could be caused by altered protein binding in
      serum and/or the time dependent changes in the permeability of biological
      membranes involved in the production of saliva.

PMID- 7646571
TI  - Synthesis and analytical profile of the new potent antibronchospastic agent 7
      [(2,2-dimethyl)propyl]-1-methyl xanthine.
AB  - 7-[(2,2-Dimethyl)propyl]-1-methyl xanthine (CAS 155006-67-0, MX2/120) is a new
      potent antibronchospastic agent with negligible side effects. The synthesis
      involves the alkylation of 3-benzyl-1-methyl xanthine with neopentyl bromide
      followed by removal of the benzyl protecting group. Main physico-chemical
      properties were determined using NMR, MS, IR, UV spectra and X-ray crystal
      structure. A quantitative determination of substances related to MX2/120 and of
      residual solvents by means of HPLC and GC, respectively, is described. MX2/120 is
      safely stored at room temperature for a long time.

PMID- 7646572
TI  - 3-substituted piperazinomethyl benzoxazolinones. Analgesic and anti-inflammatory
      compounds inhibiting prostaglandin E2.
AB  - Fourty-three new benzoxazolinone derivatives having a piperazinomethyl group at
      the third position of the ring were synthesized by using appropriate
      benzoxazolinones and 4-substituted piperazines via a Mannich reaction. The
      structures of the compounds were elucidated by spectral data and microanalyses.
      Analgesic activities were evaluated by a modified Koster test. All compounds,
      except 7, 14, 21, 32, and 41, showed analgesic activity higher than that of
      acetylsalicylic acid. The compounds were also screened for their anti
      inflammatory activity using a carrageenan paw edema test, and those exhibiting
      high anti-inflammatory activity were investigated for their ability to inhibit
      prostaglandin E2 induced paw edema. The results of anti-inflammatory testing
      indicated that most of the compounds were more active than indometacin.
      Ulcerogenic activities of the compounds were also studied and no gastrointestinal
      bleeding was observed at the 100 mg/kg dose level.

PMID- 7646573
TI  - Effects of flavonoids on parietal cell acid secretion, gastric mucosal
      prostaglandin production and Helicobacter pylori growth.
AB  - The effect of the flavonoids flavone, flavanone and quercetin on parietal cell
      acid production, H+/K(+)-ATPase activity, gastric mucosal prostaglandin E2
      biosynthesis and Helicobacter pylori growth was studied. All flavonoids inhibited
      acid production in isolated parietal cells in response to histamine and dibutyryl
      cAMP stimulation (IC50 values between 26 and 139 mumol/l) and inhibited H+/K(+)
      ATPase activity. Inhibition of H+/K(+)-ATPase activity was dependent on the ATP
      concentration. Fluorescence measurements showed that flavanone reacts with ATP.
      These findings indicate that the inhibitory action of flavonoids on H+/K(+)
      ATPase activity is related to their ability to complex ATP. Flavone and flavanone
      (10 and 100 mumol/l) stimulated prostaglandin E2 production in isolated gastric
      mucosal cells. Furthermore, the compounds inhibited Helicobacter pylori growth in
      a concentration-dependent manner. From these finding it appears that flavonoids
      are a group of compounds which could have a therapeutic potential for treatment
      of gastrointestinal diseases associated with Helicobacter pylori infection.

PMID- 7646574
TI  - [Protective effect of omeprazole against low-dose acetylsalicylic acid.
      Endoscopic controlled double-blind study in healthy subjects].
AB  - Protective Effects of Omeprazole against Low-dose Acetylsalicylic Acid/An
      endoscopic controlled double-blind study in healthy volunteers. In a randomized
      double-blind parallel study the gastroduodenal tolerability of 300 mg
      acetylsalicylic acid (CAS 50-78-2, ASA) daily (8 p.m.) has been evaluated in the
      presence of 20 mg and 40 mg omeprazole (CAS 73590-58-6) daily (8 p.m.) or placebo
      in 36 healthy volunteers using upper GI-endoscopy. The treatment periods lasted
      14 days. Endoscopic controls were performed at entry and repeated at day 14. At
      entry the mean endoscopic score averaged 0.9 +/- 0.08 in the ASA/placebo (n =
      12), the ASA/omeprazole 20 mg (n = 12) and the ASA/omeprazole 40 mg group (n =
      12). The median values were 1.0. In the placebo experiments 300 mg ASA daily
      induced marked gastroduodenal lesions at day 14 (12.4 +/- 1.7). The median value
      was 10.0. Concomitant administration of 20 mg omeprazole daily afforded
      significant protection against 300 mg ASA daily on day 14 (2.9 +/- 0.9) (p <
      0.0005 vs. ASA/placebo). 300 mg ASA + 40 mg omeprazole daily reduced the damaging
      score to 1.8 +/- 0.5 (p < 0.00002 vs. ASA/placebo). The median values in the
      ASA/omeprazole 20 mg and in the ASA/omeprazole 40 mg group were 1.0. The
      difference in the damaging score between ASA/omeprazole 20 mg and ASA/omeprazole
      40 mg after 14 days did not reach statistical significance. Our data suggest that
      coadministration of 20 mg omeprazole daily reduces almost completely
      gastroduodenal lesions evoked by 300 mg ASA.

PMID- 7646576
TI  - Mechanism of the hyperthermic effect of the novel thyrotropin-releasing hormone
      analogue Na-((1S,2R)-2-methyl-4-oxocyclopentylcarbonyl)-L-histidyl-L- prolinamide
      monohydrate in mice with reserpine-induced hypothermia.
AB  - To investigate the mechanism of the antagonistic effect of Na-((1S,2R)-2-methyl-4
      oxocyclopentylcarbonyl)-L-histidyl-L-prolin amide monohydrate (CAS 131404-34-7,
      JTP-2942) on reserpine-induced hypothermia, the role of the autonomic nervous
      system, adrenal gland, and thyroid gland regarding the effects of JTP-2942 has
      been studied in mice. Both phenoxybenzamine and propranolol significantly
      attenuated the hyperthermic effect of JTP-2942 on reserpine-induced hypothermia,
      although neither drug caused complete inhibition. A high dose of hexamethonium
      also significantly antagonized the hyperthermic effect of JTP-2942. The
      hyperthermic effect of JTP-2942 was almost abolished by adrenal demedullation. In
      mice with thiouracil-induced hypothyroidism, both thyrotropin-releasing hormone
      (TRH) and JTP-2942 significantly increased the rectal temperature. However, the
      increase induced by TRH was smaller in hypothyroid mice than in control mice,
      while the temperature increase induced by JTP-2942 was similar in both
      hypothyroid and control mice. These results suggest that the hyperthermic effect
      of JTP-2942 is mainly mediated by the adrenal gland and the autonomic nervous
      system. In addition, the hypothalamic-pituitary-thyroid axis does not regulate
      the hyperthermic effect of JTP-2942, unlike that of TRH.

PMID- 7646575
TI  - Clinical efficacy of pravastatin for hyperlipidemia in patients with type 2
      diabetes mellitus.
AB  - The efficacy of pravastatin (CAS 81131-70-6) on serum lipid levels in 91 type 2
      diabetic patients with mean glycosylated hemoglobin of 8.5% was investigated up
      to 12 weeks. Oral administration of 10 to 20 mg/d of pravastatin significantly
      decreased total cholesterol by 18.4 +/- 1.5% after 4 weeks. When analyzed
      separately in type IIa and IIb hyperlipidemia, the reduction of total cholesterol
      by pravastatin was more prominent in the former. Low-density lipoprotein
      cholesterol were also significantly decreased 22.2 +/- 2.7% after 4 weeks. The
      effect of pravastatin in reducing triglyceride was more prominent in patients
      with higher triglyceride compared to those with lower triglyceride before the
      administration of the drug. High-density lipoprotein cholesterol showed a slight
      but significant increase by 4.2 +/- 1.9% after 4 weeks. Among the apolipoproteins
      examined, apolipoprotein B was significantly decreased after 4 weeks. Atherogenic
      index and apolipoprotein B/apolipoprotein A-I ratio were also significantly
      decreased after 4 weeks. The efficacy of pravastatin was also observed after 12
      weeks to the same extent as after 4 weeks. No major side effects or abnormalities
      of laboratory parameters have been observed. These data lead to the conclusion
      that pravastatin is useful for the treatment of hyperlipidemia in type 2 diabetic
      patients with poor glycemic control without major adverse effects.

PMID- 7646577
TI  - Effects of citrulline malate on bacterial lipopolysaccharide induced endotoxemia
      in rats.
AB  - The administration of endotoxins to rats as lipopolysaccharides (LPS) induces a
      state of exhaustion, in which the main symptoms are febrile hyperthermia, reduced
      food intake, decreased body weight, and reduced muscle performance in treadmill
      tests. Underlying the physiological and behavioral disturbances due to the LPS is
      the activation of macrophages that release cytokines (interleukin-1, tumor
      necrosis factor a) and NO. The cellular responses are intended to maintain
      homeostasis. Provision of citrulline as citrulline malate (CAS 54940-97-5,
      Stimol), an antifatigue substance, improved muscle performance, but had no effect
      on the body temperature or on the body weight of these animals weakened by LPS.
      The presence of citrulline in the NO synthesis pathway, or its participation in
      the speeded up elimination of ammonia and lactates, the main products of muscle
      metabolism, might explain the effects of citrulline malate in rats treated with
      LPS.

PMID- 7646578
TI  - Determination of the new fluoroquinolone balofloxacin and its metabolites in
      biological fluids by high performance liquid chromatography.
AB  - A sensitive high performance liquid chromatographic method for the determination
      in biological fluids of 1-cyclopropyl-6-fluoro-1,4- dihydro-8-methoxy-7-(3
      methylaminopiperidin-1-yl)-4-oxoquinoline-3 -carboxylic acid dihydrate (CAS
      127294-70-6, balofloxacin, Q-35), a new fluoroquinolone, as well as its
      metabolites, has been developed. Balofloxacin and its metabolite, N-desmethyl
      balofloxacin, were separated and determined by reversed-phase column with
      fluorescence detection. Balofloxacin glucuronide was determined as balofloxacin
      after alkali hydrolysis. This method exhibited good precision and accuracy.
      Furthermore, it is a simple method and requires only a small amount of samples,
      and therefore should be useful for pharmacokinetic studies in animals and humans.

PMID- 7646579
TI  - Pharmacokinetics of the new fluoroquinolone balofloxacin in mice, rats, and dogs.
AB  - The pharmacokinetics of 1-cyclopropyl-6-fluoro-1, 4-dihydro-8-methoxy-7-(3
      methylaminopiperidin-1-yl)-4-oxoquinoline -3-carboxylic acid dihydrate (CAS
      127294-70-6, balofloxacin, Q-35), a new fluoroquinolone, were studied in mice,
      rats and dogs by high performance liquid chromatography. The mean oral
      bioavailabilities of balofloxacin calculated from the area under the curve after
      oral and intravenous administration in mice, rats and dogs were 19.03, 87.50 and
      87.73%, respectively, indicating that balofloxacin was almost completely absorbed
      in rats and dogs but not in mice after single oral administration. The mean
      elimination half-lives in plasma after intravenous administration in mice, rats
      and dogs were 0.92, 1.33 and 6.38 h, respectively. Mean cumulative urinary
      excretion percentages of unchanged balofloxacin within 24 h of oral
      administration of balofloxacin at the dose of 20 mg/kg in mice, rats and dogs
      were 4.91, 21.77 and 22.49% of the dose, respectively. A small portion of the
      metabolite was excreted into urine as balofloxacin glucuronide and N-desmethyl
      balofloxacin in these species. After oral administration of balofloxacin at the
      dose of 100 mg/kg to rats, absorption was prolonged compared with that after
      administration at the doses of 5 and 20 mg/kg. Plasma concentration-time profiles
      and pharmacokinetic parameters of balofloxacin in male rats were similar to those
      in female rats, indicating no sex-related differences. Once daily 21-day multiple
      administrations had not affect on these pharmacokinetic profiles of balofloxacin
      in rats.

PMID- 7646580
TI  - [In vitro activity of sparfloxacin against methicillin-resistant staphylococci].
AB  - The antimicrobial activity of sparfloxacin (CAS 110871-86-8) against 154 clinical
      isolates of methicillin-resistant staphylococci was investigated and compared
      with that of 6 other fluoroquinolones. The isolates consisted of 100 methicillin
      resistant Staphylococcus aureus (MRSA), 29 Staphylococcus epidermidis (MRSE) and
      25 other coagulase-negative staphylococci (CNS). Sparfloxacin was more active
      than ciprofloxacin and the other fluoroquinolones against all strains tested. The
      MIC90 of sparfloxacin against the 100 isolates of Staphylococcus aureus was 8
      mg/l, while that of ciprofloxacin was > or = 64 mg/l. Moreover, ciprofloxacin
      susceptible MRSA isolates were inhibited by sparfloxacin at a concentration of <
      or = 0.06 mg/l. The other quinolones had an MIC90 ranging from 0.5 mg/l to 4 mg/l
      against ciprofloxacin-susceptible MRSA. Similar results were obtained for the
      MRSE and CNS isolates tested. As many as 90% of the ciprofloxacin-susceptible
      microorganisms were inhibited at a concentration of < or = 0.06 mg/l or 0.125
      mg/l of sparfloxacin. The MIC90 of sparfloxacin against ciprofloxacin-resistant
      CNS and MRSE were 4 mg/l and 8 mg/l, respectively. Sparfloxacin was clearly more
      active than any of the other quinolones against all species tested, although
      higher concentrations were needed to inhibit ciprofloxacin-resistant
      staphylococci.

PMID- 7646581
TI  - Rational approach to fractionation, isolation, and characterization of
      polysaccharides from the lichen Cetraria islandica.
AB  - Polysaccharides, isolated from the lichen Cetraria islandica, have antimicrobial
      effectiveness. For pharmaceutical applications the two glucan components lichenan
      and isolichenan as well as the galactomannan component are of actual interest.
      Especially the a-glucan isolichenan ist used as an active ingredient in cough
      lozenges. The conditions for the extraction of the raw material, mainly pH and
      temperature, have a strong influence on the yield of lichenan, isolichenan, and
      galactomannan, and also on the amount of tannins in the extract. Target products
      and also by-products give higher extraction yields with increasing extraction
      temperatures. Hot water extraction with subsequent fractionation of the extracted
      polysaccharides by multiple freezing/thawing steps and water removal applying
      ethanol and ether permitted the isolation of the target polysaccharides in
      preparative quantities. Tannins were removed by reversed phase chromatography. IR
      and NMR spectroscopy were used for structural characterization of lichenan and
      isolichenan. After optimization of the hot water extraction process no
      significant lower extraction and fractionation yields have been obtained compared
      to the established tricky DMSO extraction procedure.

PMID- 7646582
TI  - [Exercise for strengthening of the back in patients with low back pain--a new
      fad?].

PMID- 7646583
TI  - Laser therapy of Barrett's mucosa.

PMID- 7646584
TI  - The design of trials for prevention of IDDM.
AB  - Several large clinical trials for the prevention of IDDM in islet cell antibody
      positive first-degree relatives are planned or underway. The design of these
      trials rests in part on assumptions about the natural history of autoimmunity
      during the prediabetic period and on the likely effectiveness of the intervention
      being tested. At this time, most of the factors that influence the required
      sample size can only be roughly estimated.

PMID- 7646585
TI  - [Of course we should save fetuses of brain-dead women!].

PMID- 7646586
TI  - [Prevention and treatment of osteoporosis. A review of different methods].
AB  - This article reviews a number of methods for the treatment and prevention of
      osteoporosis. A preventive treatment achieves the best effect if it is started as
      soon after menopause as possible. Hormone substitution treatment has in many
      trials been shown to be effective in stopping the post-menopausal
      demineralization of the skeleton. Calcitonin is suggested as an alternative to
      hormone substitution, however this substance is still not registered in Denmark
      for this purpose. There are today several possible treatments for symptomatic
      osteoporosis; however, the long-term effect on frequency of new fractures remains
      to be confirmed. The regulation of a number of "life-style factors" such as diet
      and exercise is part of both the prevention and treatment of osteoporosis.

PMID- 7646587
TI  - Nd:YAG "sweeping"--an indirect technique for clearing intraocular lens deposits.
AB  - Corticosteroid-resistant deposits on the anterior surface of intraocular lenses
      (IOLs) in 11 patients who had complained of poor vision were "swept" with a
      Neodymium:YAG laser beam. As contrasted with previous "direct hit" methods, our
      method is indirect, using a low-power, defocused beam to generate an acoustic
      shock-wave, which then sweeps the lens surface clear of deposits. The deposits
      were cleared in all 11 patients, with no damage to the IOL or any other postlaser
      complications. Improvement in visual acuity ranged from 1 to 3 lines, and all the
      patients reported alleviation of symptoms.

PMID- 7646588
TI  - [10 years chorionic villi sampling and the pros and cons of amniocentesis].

PMID- 7646589
TI  - Critical thinking: a foundation for consumer-focused care.
AB  - Both providers and recipients of health care services are now focusing attention
      on not only what is provided but also how services are provided. The goal is
      consumer satisfaction, with pressure on the provider of services to meet customer
      demands. This shift in focus challenges the knowledge and skills of nurses, and
      their ability to solve problems in collaboration with their customers. To provide
      consumer-focused care, nurses will need to develop critical thinking skills that
      utilize logical/analytical and intuitive/creative approaches to solving problems.
      Critical thinking skills that integrate these two approaches will provide
      practitioners expertise in flexible, individualized, and situation-specific
      problem solving. Nursing staff who are able to focus on the consumer will be
      better prepared to meet the demands of today's competitive health care market.
      The challenge facing educators is to prepare nurses with a foundation from which
      to provide this care.

PMID- 7646590
TI  - [Discussion about foreign nurses. A challenge to Norwegian nurses].

PMID- 7646591
TI  - Noninvasive testing in the diagnosis of osteomalacia.
AB  - PURPOSE: Osteomalacia is associated with many clinical, radiographic, and
      biochemical abnormalities. Unfortunately, none of these are pathognomonic of the
      disorder, and histologic examination of a bone biopsy specimen is often necessary
      to confirm the diagnosis. Noninvasive methods of diagnosis would be preferable to
      decrease patient morbidity and increase cost-effectiveness. Previous studies
      addressing the adequacy of these methods were performed prior to the widespread
      availability of 1,25-dihydroxycalcitriol (1,25-(OH)2D3) and parathyroid hormone
      (PTH) levels. Therefore, we reviewed our experience with patients with biopsy
      proven osteomalacia to determine if PTH or 1,25(OH)2D3 levels would serve a
      useful role in establishing the diagnosis of osteomalacia. METHODS: We
      retrospectively studied 17 patients who had biopsy-proven osteomalacia (defined
      as an osteoid volume greater than 10% and an osteoid width greater than 15
      microns) in order to ascertain if their clinical presentation, biochemical
      profile, and radiographic features were sufficient to establish a diagnosis of
      osteomalacia. RESULTS: We found that 94% of our patients exhibited symptoms of
      osteomalacia, and all patients had at least one demonstrable sign of osteomalacia
      on examination. Biochemically, the patients presented a heterogeneous picture:
      94% had an elevated alkaline phosphatase level; 47% had either a low serum
      calcium or phosphate (12% had both) level; urinary calcium excretion was low in
      18%; and 25-(OH)D3 concentration was low in 29%. Levels of 1,25-(OH)2D3 were
      measured in eight patients; three had low values despite normal 25-(OH)D3 levels.
      PTH levels were elevated in 41% of patients in the absence of histologic evidence
      of hyperparathyroidism; however, these patients were noted to have multiple other
      abnormal clinical, biochemical, or radiograph features. Radiographically, 18% of
      patients had pseudofractures; the rest had nonspecific findings suggestive of
      osteomalacia. In summary, all patients had at least two of the following
      abnormalities: low calcium, low phosphate, elevated alkaline phosphatase, or a
      radiographic finding suggestive of osteomalacia. CONCLUSION: We conclude: (1) a
      careful history and physical examination remain important in the evaluation of
      potential osteomalacia patients; (2) PTH offered no apparent benefit as a
      screening test in our patients; (3) 1,25-(OH)2D3 was low in three patients with
      normal levels of 25-(OH)D3; (4) decreased urinary calcium excretion had low
      sensitivity for detecting osteomalacia; and (5) serum calcium, phosphate,
      alkaline phosphatase, and radiographic examination may be adequate screening
      tests in patients who have a clinical presentation suggestive of osteomalacia.

PMID- 7646592
TI  - [The right to information in clinical practice].

PMID- 7646593
TI  - [Prevalence of obesity in Spain].
AB  - BACKGROUND: Obesity constitutes a severe public health problem due to both its
      complications as a morbid entity and its association to different chronic
      diseases. The aim of the present study was to calculate the prevalence of obesity
      in the Spanish adult population. METHODS: With the information concerning weight
      and height of a representative population sample of Spanish adults over the age
      of 20 obtained from the computerized data base of the National Survey of Spanish
      Public Health, Quetelet's index was calculated as an estimation of obesity.
      RESULTS: 7.8% of the Spanish adult population may be considered as obese. Obesity
      is more frequent in individuals from 55 to 64 years of age, in females and in
      those with a lower education. CONCLUSIONS: From estimations performed from self
      declared data concerning weight and height, obesity was found to be more frequent
      in the population from 45 to 74 years of age, in females and in those of low
      socioeconomic levels.

PMID- 7646594
TI  - [Arterial hypertension: where are we and where are we heading to?].

PMID- 7646595
TI  - Intercept studies, clinical trials, and cluster experiments: to whom can we
      extrapolate?
AB  - While sample surveys rely on an explicit theory of the relationship between a
      sample and its reference population, many nonsurvey-based designs lack a clear
      relationship to the population to which inferences are to be drawn. For example,
      in order to be applicable to large populations, intercept studies--which include
      observational studies of migrant populations and randomized studies such as mall
      intercepts--must make implicit or explicit assumptions about the probability of
      finding members of the population. In conducting clinical trials, constraints
      imposed by the research often lead large segments of the population to have zero
      probability of observation. Although such experiments generally conduct research
      at only a few sites, investigators usually intend to apply their results quite
      broadly. This paper compares intercept studies and clinical trials with
      particular emphasis on inference to a population for which the probabilities of
      being observed are unknown, unreliable, or very small.

PMID- 7646596
TI  - Snare fracture during endoscopic papillectomy.

PMID- 7646598
TI  - [Investigation on nursing in Spain. Task group on nursing].

PMID- 7646597
TI  - [CD4+ lymphocytes and opportunistic infections and neoplasms in patients with
      human immunodeficiency virus infection].
AB  - BACKGROUND: The CD4+ lymphocytes are the principal target cell for the human
      immunodeficiency virus (HIV). Their depletion originates a very severe cell
      immunosuppression, which conditions the appearance of opportunistic infections
      and neoplasms characteristic of AIDS. The aim of this study was to evaluate
      whether there is a relation between the degree of cell immunosuppression and the
      type of opportunistic infections and neoplasms which these patients develop in
      Spain. METHODS: The CD4+ lymphocyte counts in 400 adults with HIV infection who
      developed opportunistic infections or neoplasms were retrospectively reviewed
      (1987-1991). This determination was carried out during between two months prior
      to diagnosis of AIDS (CDC, 1987) to one month after such diagnosis. RESULTS: The
      results allowed opportunistic infections to be classified into three groups
      according to the grade of immunosuppression: 1) opportunistic infections with
      more than 0.2 x 10(9) CD4+ lymphocytes/l (45-60% of cases of tuberculosis,
      esophageal candidiasis and enteritis by Isospora belli); 2) opportunistic
      infections with 0-0.2 x 10(9) CD4/l (87-100% of the cases of pneumonia by
      Pneumocystis carinii, encephalic toxoplasmosis, visceral leishmaniasis and
      enteritis by Cryptosporidium); 3) opportunistic infections with 0-0.1 x 10(9) CD4
      lymphocytes/l (70-100% of the cases of systemic cryptococcosis, retinitis by
      cytomegalovirus, progressive multifocal leukoencephalopathy and infection by
      Mycobacterium avium-intracellulare). With respect to the neoplasms, Kaposi's
      sarcoma was observed in patients with different degrees of immunosuppression.
      Seventy-five and 80% of the patients with non Hodgkin's lymphoma and primary
      cerebral lymphoma had less than 0.2 x 10(9)/l and less than 0.1 x 10(9)/l CD4+
      lymphocytes, respectively. CONCLUSIONS: The CD4 lymphocyte counts may predict the
      type of opportunistic infections which patients with the human immunodeficiency
      virus infection may develop.

PMID- 7646599
TI  - [Encephalopathy following poisoning with an anticholinergic agent].
AB  - A 55-year-old chemical laboratory technician developed mydriasis and ocular
      hypertension, which lasted for 6 weeks, after synthesizing several kilograms of a
      scopolamine-related test agent with anticholinergic action and then decanting a
      powdery intermediary substance, the dust of which he may have inhaled. Six weeks
      later he suddenly had symptoms of an acute intoxication while synthesizing a
      scopolamine-related substance. The anticholinergic delirium regressed completely
      within one day requiring no treatment. But subsequently he developed symptoms of
      a toxic encephalopathy. This only partially regressed over the following 3 years.
      Its probable cause is thought to have been either the manifestation of an already
      existing organic cerebral psychiatric syndrome or an as yet unknown effect of the
      test substance.

PMID- 7646600
TI  - [Transitional carcinoma of the bladder. Evaluation of prognostic factors].
AB  - This study evaluates prognostic factors in 25 patients with transitional cell
      carcinoma (TCC) of the bladder with a minimum follow up of two years.
      Histologically there were 12 patients with grade I tumors according to the
      Mostofi's classification, 10 patients with grade II lesions and 3 grade III. The
      course of the grade I and II tumors was similar and the grade III worse.
      According to stage, there were 11 patients stage 0, 8 stage A, 3 stage B and 3
      stage C. Patients with all stages recurred but only those with stage B and C died
      of their disease. In 18 patients the expression of the beta subunit of HCG and of
      the blood group isoantigens was demonstrated by immunohistochemistry. There were
      8 negative cases and 10 positive for the beta subunit of HCG and 10 negative and
      8 positive for the blood group isoantigens. DNA analysis was done with an image
      analyzer on cytological smears of the urine in the 25 cases after decolorization
      of the smears and Feulgen staining. There were 5 diploid and 25 aneuploid cases.
      The DNA malignancy grade was determined with a range between 0.100 and 2.689 and
      the number of events more than 5c (5N). The presence of HCG, aneuploid tumors, a
      malignancy grade higher than 0.500 and the presence of events more than 5c were
      statistically significant unfavorable prognostic factors. The presence of blood
      group isoantigens was associated with a better evolution of the tumor but did not
      reach statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7646601
TI  - Bilateral vocal cord paralysis following endotracheal intubation.

PMID- 7646602
TI  - [Suicide in Denmark over 70 years, 1922-1991. General tendencies].
AB  - The frequency of suicide in Denmark has been studied for a period of 70 years.
      Rates of suicide per 100,000 inhabitants, 15 years and over, by age and sex have
      been calculated, the calculation being based on data from the Danish Cause-of
      Death statistics and from the Population statistics provided by Danmarks
      Statistik. Although the frequency of suicide has varied during the period under
      study, the overall trend has been one of significant increase. The increase is in
      great part due to the fact that an increasing number of women, especially women
      in their 50s, commit suicide. The increase in male rates is more evenly
      distributed over all age groups and, contrary to what is the case for women, the
      age-effect is still strong for men.

PMID- 7646603
TI  - Prediction of radiotherapy response using SF2: why it may work after all.

PMID- 7646604
TI  - [Percutaneous punch biopsy of pulmonary nodules with a co-axial system].

PMID- 7646605
TI  - Mouth-operated mucus extractors: safe to use?

PMID- 7646606
TI  - Impossibility to cross a stenotic mitral valve with the Inoue balloon: success
      with a modified technique.

PMID- 7646607
TI  - Classification and epidemiology of systemic vasculitis.

PMID- 7646608
TI  - [Combined kidney and pancreas transplantation in late-stage diabetes].

PMID- 7646609
TI  - Human chorionic gonadotropin supplementation in recurring pregnancy loss: a
      controlled trial.
AB  - OBJECTIVES: To investigate the efficacy of hCG in the management of recurrent
      early pregnancy loss. DESIGN: A prospective, randomized, controlled trial.
      SETTING: Miscarriage Clinic, Women's Hospital, Liverpool, United Kingdom.
      SUBJECTS: Eighty-one women attending the miscarriage clinic with idiopathic
      recurrent pregnancy loss were randomized to receive hCG supplementation or
      placebo in early pregnancy. MAIN OUTCOME MEASURE: The success rate or live birth
      rate. RESULTS: In women with regular menstrual cycles it was found that hCG had
      no beneficial effect, the pregnancy success rate being 86% in both groups.
      However, women with oligomenorrhea had a pregnancy success rate of 40% in the
      placebo group but a statistically significant improvement to 86% if hCG was
      given. CONCLUSIONS: Human chorionic gonadotropin can be recommended for
      idiopathic recurrent pregnancy loss in women with oligomenorrhea.

PMID- 7646610
TI  - Paracervical anesthesia for outpatient hysteroscopy.
AB  - One hundred seventy-seven women aged 41 +/- 8 (mean +/- SD) years, referred for
      evaluation of excessive uterine bleeding, were enrolled in an open-label
      randomized trial to evaluate the efficacy of local anesthesia before hysteroscopy
      in an outpatient population. The patients underwent hysteroscopy and endometrial
      biopsy with paracervical block by 10 mL of 1% mepivacaine hydrochloride solution
      (n = 87) or no local anesthesia (n = 90) and assessed lower abdominal and pelvic
      pain according to a 10-point linear analog scale. The mean +/- SD pain score was
      4.5 +/- 2.0 at hysteroscopy and 5.2 +/- 2.1 at endometrial biopsy in the 87
      subjects given a paracervical block versus 4.9 +/- 2.2 and 5.7 +/- 2.4 in the 90
      women not given local anesthesia, without statistically significant differences.
      Paracervical anesthesia for routine outpatient hysteroscopy in premenopausal
      women may be superfluous.

PMID- 7646611
TI  - In-vitro and in-vivo activity of DWC-751, a new cephalosporin.

PMID- 7646612
TI  - [Anti-decubitus mattress].

PMID- 7646613
TI  - [Secondary amenorrhea. Diagnostic orientation].

PMID- 7646614
TI  - Prevention of occupational transmission of human immunodeficiency virus and
      hepatitis B virus among anesthesiologists: a survey of anesthesiology practice.
AB  - In light of the increasing prevalence of the human immunodeficiency virus (HIV)
      and hepatitis B virus (HBV), anesthesiologists are now likely to see more
      patients who are at high risk for these viruses. Therefore, it is important that
      they adopt infection control policies aimed at preventing occupational
      transmission of these and other pathogens during their clinical practice. This
      study was designed, using a questionnaire format, to evaluate anesthesiologist
      compliance with Centers for Disease Control (CDC) guidelines for the prevention
      of occupational transmission of HIV and HBV. A total of 1149 questionnaires were
      mailed to anesthesiologists randomly selected from the members' directory of the
      American Society of Anesthesiologists (ASA). Of these, 493 (44%) were completed
      and returned. Eighty-eight percent of respondents reported that they always
      complied with CDC guidelines when presented with an HIV-infected patient, but
      only 24.7% adhered to the guidelines when the patient was considered low risk (P
      < 0.01). This trend was also reflected in the use of gloves and other protective
      wear in the perioperative period. Although 70% of respondents indicated that they
      recapped needles on a regular basis, this practice was not associated with an
      increased incidence of needlestick injuries. However, anesthesiologists who
      reported recapping needles using the one-handed technique were less likely to
      sustain a needlestick injury than those who recapped using the two-handed
      technique. Thirty-one percent and 72% of respondents respectively reported a
      clean or contaminated needlestick within the preceeding 12 mo. Only 45.4% of
      those receiving a contaminated needlestick sought treatment.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7646615
TI  - Retrieval of an entrapped guide wire with a braiding maneuver.

PMID- 7646616
TI  - On the photodynamic therapy action spectrum of zinc phthalocyanine tetrasulphonic
      acid in vivo.
AB  - The photodynamic therapy (PDT) activity of zinc phthalocyanine tetrasulphonic
      acid in a rodent tumour model was shown to be critically dependent on the
      wavelength of the excitation laser light over a relatively small wavelength
      range. Thus the sensitizer showed a doubling of the PDT activity with
      fibrosarcoma LSBD1 in BDIX rats when the wavelength of the illuminant was
      displaced from 680 to 692 nm. Under these conditions, the sensitizer is
      approximately three times more effective than polyhaematoporphyrin, whereas
      previously it has been considered to be of low PDT activity. This wavelength
      effect is attributed to a red shift of the absorption spectrum of the sensitizer
      in cells compared with that in solution. Fluorescence excitation studies with
      sensitizer absorbed in mouse 3T3 fibroblast cells are consistent with such a red
      shift.

PMID- 7646617
TI  - Physician-patient communication. A key to malpractice prevention.

PMID- 7646618
TI  - Randomised trial of early tapping in neonatal posthaemorrhagic ventricular
      dilatation: results at 30 months.

PMID- 7646619
TI  - Bronchopleural fistula after pneumonectomy with a hand suture technique.
AB  - We have reviewed the incidence of bronchopleural fistula among 530 consecutive
      pneumonectomies, all carried out by one surgical team using a uniform suture
      technique between January 1980 and November 1993. There were 7 fistulas (1.3%);
      all of them occurred within 15 days postoperatively. There were no cases of late
      fistula during a mean follow-up period of 23 months. The pathology for which
      pneumonectomy was undertaken was primary lung malignancies in 488 cases (92.1%),
      metastatic disease in 15 cases (2.8%), and benign diseases in 27 cases (5.1%).
      All fistulas developed after pneumonectomy for lung cancer. Other risk factors
      included age, preoperative radiotherapy, and the surgeon's level of experience,
      as only two fistulas occurred with the consultant who performed 410
      pneumonectomies (0.5%). The bronchial stump was free of tumor in all cases. There
      were no fistulas in the 37 completion pneumonectomies (7%). All fistulas were
      treated within 2 days of diagnosis by resuturing the stump through the initial
      thoracotomy incision. That was successful in 5 patients, whereas fatal
      complications developed in the other 2 patients. We believe that suture closure
      of the bronchial stump at pneumonectomy provides a cheap and reliable technique
      that gives good results in all situations.

PMID- 7646620
TI  - A credo for ethical managed care in mental health practice.

PMID- 7646621
TI  - [Comments of the new regulations concerning clinical trials].

PMID- 7646622
TI  - [People should be valued equally, regardless of where they live].

PMID- 7646623
TI  - The acute respiratory distress syndrome.
AB  - ARDS is a complex response of the lung to direct (inhalational) and indirect
      (hematogenous) insults. It is easy to be pessimistic about the benefit of the
      approaches we have described, but there is evidence that overall survival has
      improved in recent years. To maintain this progress, new therapies for ARDS must
      be rigorously evaluated, and their routine use should be recommended only after
      careful scrutiny of the evidence. Such a course will eliminate the unnecessary
      risks and costs often associated with unproved therapies.

PMID- 7646624
TI  - [Observations concerning hallucination research in France at the beginning of the
      19th century: the role of self-medication].

PMID- 7646625
TI  - [Early surgical treatment of biliary atresia].

PMID- 7646626
TI  - Coagulation activity is increased in the left atrium of patients with mitral
      stenosis.
AB  - OBJECTIVES: This study investigated the hemostatic status of the right and left
      atria in patients with mitral stenosis. BACKGROUND: Systemic thromboembolism is a
      serious major complication in patients with mitral stenosis. However, the
      pathogenesis of thromboembolism in mitral stenosis is not fully understood.
      METHODS: We determined the plasma levels of biochemical markers for platelet
      activity (platelet factor 4 and beta-thromboglobulin) and status of thrombin
      generation (fibrinopeptide A and thrombin-antithrombin III complex) and
      fibrinolysis (D-dimer and plasmin-alpha 2-plasmin inhibitor complex) in specimens
      of blood obtained from the peripheral vein and right and left atria of 12
      consecutive patients with mitral stenosis who were undergoing percutaneous mitral
      valvuloplasty. RESULTS: Plasma levels of platelet factor 4, beta-thromboglobulin,
      D-dimer and plasmin-alpha 2-plasmin inhibitor complex in the patients did not
      differ significantly between the right and left atria, whereas levels of
      fibrinopeptide A and thrombin-antithrombin III complex in the left atrium were
      significantly higher than those in the right atrium (fibrinopeptide A in the left
      and right atria 19.35 +/- 4.64 and 6.31 +/- 0.75 ng/ml [mean +/- SE],
      respectively, p < 0.02; thrombin-antithrombin III complex in the left and right
      atria 11.45 +/- 2.29 and 3.98 +/- 0.60 ng/ml, respectively, p < 0.01). Levels of
      fibrinopeptide A and thrombin-antithrombin III complex in the left atrium did not
      correlate with mean transmitral gradient, dimension of the left atrium or
      reciprocal of the mitral valve area. Peripheral blood plasma levels of von
      Willebrand factor antigen were significantly higher in the patients than in an
      age-matched control group of normal subjects (168 +/- 25% and 99 +/- 7%,
      respectively, p < 0.05) but showed no difference in the peripheral blood and
      right and left atria of the patients. CONCLUSIONS: The coagulation system is
      activated in the left atrium of patients with mitral stenosis even during
      anticoagulation.

PMID- 7646627
TI  - Efficacy of prophylactic antibiotics for craniotomy: a meta-analysis.
AB  - A meta-analysis of published randomized studies comparing prophylactic
      antibiotics to placebo in craniotomies was performed. Ten studies were examined;
      eight met criteria for inclusion into the meta-analysis. The analysis showed an
      advantage of antibiotics over placebo at the P < 10-8 level. Tests for
      homogeneity of effect size between the individual studies showed similar effects
      of antibiotic treatment between trials, despite variation in the randomization
      methods and antibiotic regimens used. No statistically significant difference was
      detected between antibiotic regimens that did or did not cover gram-negative
      organisms or between single- and multiple-dose regimens. Cumulative meta-analyses
      showed that this conclusion could have been confidently drawn by 1988, after only
      four of the eight eligible trials had been published. Trials published since that
      time have reinforced these conclusions but have not significantly altered them.
      Future studies should compare proposed new antibiotic regimens with one of those
      already demonstrated to be effective, not with a placebo.

PMID- 7646628
TI  - Evidence for functional sympathetic reinnervation of left ventricle and coronary
      arteries after orthotopic cardiac transplantation in humans.
AB  - BACKGROUND: Structural sympathetic reinnervation of the transplanted human heart
      is believed to occur > 1 year after cardiac transplantation. The functional
      effects of reinnervating neurons, however, are undefined. METHODS AND RESULTS: To
      test directly for functional sympathetic reinnervation, we measured left
      ventricular or coronary hemodynamics in 11 patients < or = 4 months after
      transplantation, in 45 patients > or = 1 year after transplantation, and in 13
      untransplanted, normally innervated patients. Sympathetic neurons were stimulated
      with left coronary injection of tyramine (10 micrograms/kg), which causes
      norepinephrine release from intact sympathetic nerve terminals. Reinnervation was
      defined as a measure of cardiac norepinephrine release after intracoronary
      tyramine injection. Left ventricular pressure was measured before and at 1-minute
      intervals after tyramine with a micromanometer-tipped catheter (Millar
      Instruments). Coronary blood flow velocity (CBFV) was measured with a 3F Doppler
      catheter (Numed), and coronary artery cross-sectional area was calculated using
      quantitative coronary angiography. In both early patients and patients studied >
      or = 4 months after transplantation without reinnervation (late denervated),
      there was no change in left ventricular function in response to tyramine (delta
      dP/dt = 31 +/- 61 and 49 +/- 54 mm Hg/s, respectively; P = NS). In transplant
      recipients with reinnervation (late reinnervated), left ventricular dP/dt rose
      significantly (delta dP/dt = 210 +/- 97 mm Hg/s; P < .05) but less than in
      healthy patients (delta dP/dt = 577 +/- 66 mm Hg/s; P < .05). In both early and
      late denervated patients, there was no change in CBFV in response to tyramine
      (CBFV = 1.02 +/- 0.1 and 1.0 +/- 0.1 x basal, respectively; P = NS). In late
      reinnervated patients, CBFV fell significantly (CBFV = 0.94 +/- 0.1 x basal; P <
      .05). In healthy patients, CBFV fell even more (CBFV = 0.88 +/- 0.1 x basal; P <
      .05). CONCLUSIONS: Stimulation of reinnervating sympathetic neurons with tyramine
      in transplant recipients causes a significant but subnormal increase in dP/dt and
      a transient decrease in CBFV, suggesting that reinnervating sympathetic neurons
      can produce physiologically meaningful changes in left ventricular function and
      coronary artery tone.

PMID- 7646629
TI  - The Pope and the ontogeny of persons.
AB  - In his recent book Crossing the Threshold of Hope, Pope John Paul II airs his
      views on human reproduction. The pity is that he ignores most of modern genetics
      and embryology.

PMID- 7646630
TI  - Anaesthetic management for placement of a stent for high tracheal stenosis.

PMID- 7646631
TI  - Technique for harvesting the radial artery as a coronary artery bypass graft.
AB  - The radial artery was proposed and then abandoned as a coronary artery bypass
      graft in the 1970s. Development of new pharmacologic antispasmodic agents and
      minimally traumatic harvesting techniques has led to a revival of the use of the
      radial artery in coronary artery bypass procedures. Unlike the saphenous vein in
      the lower extremities, the radial artery in the volar forearm is not a
      subcutaneous structure. Safe harvest of the artery requires an understanding of
      volar forearm anatomy. Based on review of anatomy, cadaver dissection, and
      clinical experience with 40 patients, we have developed a technique for radial
      artery harvest. The volar forearm is divided into three zones: the proximal zone,
      the middle zone, and the distal zone. In each zone, important anatomic landmarks
      are identified. Our harvesting technique has resulted in minimal postoperative
      morbidity and no postoperative ischemic complications. Although the pedicled
      internal thoracic artery graft remains the primary arterial conduit for
      myocardial revascularization, the radial artery is an excellent additional bypass
      conduit.

PMID- 7646632
TI  - ["Patients consulting the physician in private practice--selected results of a
      survey of general practice"].

PMID- 7646633
TI  - Randomized trial of modified Bassini versus Shouldice inguinal hernia repair. The
      Cologne Hernia Study Group.
AB  - Between 1986 and 1992, 265 men of mean age 51 (range 16-75) years with a primary
      inguinal hernia were randomized to undergo surgery by staff surgeon or surgical
      resident and further randomized to receive a modified Bassini operation
      (transversalis fascia not divided but included in the repair) or Shouldice
      procedure. The follow-up rate was 92.1 per cent with a mean follow-up of 3.3
      years. Recurrence developed in 12 of 125 patients with a Bassini procedure and
      two of 119 after a Shouldice repair (9.6 versus 1.7 per cent, P = 0.006). The
      recurrence rate was no different for staff surgeons and trainees (5.9 versus 5.6
      per cent, P not significant). Multivariate analysis identified the presence of a
      direct hernia (P = 0.003) as the additional main factor for the development of
      recurrence.

PMID- 7646634
TI  - Possible association between Behcet's syndrome and chronic hepatitis C virus
      infection.

PMID- 7646635
TI  - [Comments on the contribution by F. Theissig et al. Metastatic malignant vipoma
      of the pancreas].

PMID- 7646636
TI  - Pattern of blood pressures among high and low altitude residents of southern
      Saudi Arabia.
AB  - The patterns of blood pressures and their correlates in 499 Saudi nationals aged
      10-72 years living at high altitude (3150 m above sea level) and 594 Saudi
      nationals aged 10-76 years living at low altitude (500 m above sea level) were
      prospectively studied. The average BPs were significantly higher in highlanders
      compared with lowlanders. In both high and lowland residents the BPs rose with
      age although males in both groups showed a drop in both SBP and DBP beyond the
      age of 50 years. Hypertension (> 160/95 mmHg) was not detected among lowlanders
      and only 1.4% of all highlanders were found to be hypertensive. These differences
      in BPs are attributed to the significantly higher body mass index values and
      packed cell volume levels in the highlanders.

PMID- 7646637
TI  - Increases in CD4 T lymphocytes with intermittent courses of interleukin-2 in
      patients with human immunodeficiency virus infection. A preliminary study.
AB  - BACKGROUND: Interleukin-2 is an important regulatory cytokine of the immune
      system, with potent effects on T cells, B cells, and natural killer cells. In
      vitro, interleukin-2 can induce the proliferation and differentiation of
      peripheral-blood mononuclear cells from patients infected with the human
      immunodeficiency virus (HIV). METHODS: We treated 25 HIV-infected patients with
      interleukin-2 administered as a continuous infusion at a dosage of 6 to 18
      million IU per day for 5 days every 8 weeks during a period of 7 to 25 months.
      All patients also received at least one approved antiviral agent. Immunologic and
      virologic variables were monitored monthly. RESULTS: In 6 of 10 patients with
      base-line CD4 counts higher than 200 per cubic millimeter, interleukin-2 therapy
      was associated with at least a 50 percent increase in the number of CD4 cells.
      Changes ranged from -81 to +2211 cells per cubic millimeter. Interleukin-2
      therapy resulted in a decline in the percentage of CD8 lymphocytes expressing HLA
      DR and an increase in the percentage of CD4 lymphocytes that were positive for
      the p55 chain of the interleukin-2 receptor. Four patients had a transient but
      consistent increase in the plasma HIV RNA level at the end of each infusion. In
      the remaining 15 patients, who had CD4 counts of 200 or fewer cells per cubic
      millimeter, interleukin-2 therapy was associated with increased viral activation,
      few immunologic improvements, and substantial toxic effects. CONCLUSIONS:
      Intermittent courses of interleukin-2 can improve some of the immunologic
      abnormalities associated with HIV infection in patients with more than 200 CD4
      cells per cubic millimeter.

PMID- 7646638
TI  - Public health impact of Rwandan refugee crisis: what happened in Goma, Zaire, in
      July, 1994? Goma Epidemiology Group.
AB  - The flight of 500,000-800,000 Rwandan refugees into the North Kivu region of
      Zaire in July, 1994, overwhelmed the world's response capacity. During the first
      month after the influx, almost 50,000 refugees died, an average crude mortality
      rate of 20-35 per 10,000 per day. This death rate was associated with explosive
      epidemics of diarrhoeal disease caused by Vibrio cholerae 01 and Shigella
      dysenteriae type 1. 3-4 weeks after the influx of refugees, acute malnutrition
      rates among children under 5 years old ranged between 18 and 23%. Children with a
      recent history of dysentery and those in households headed by women were at
      higher risk of malnutrition. A well-coordinated relief programme, based on
      rapidly acquired health data and effective interventions, was associated with a
      steep decline in death rates to 5 to 8 per 10,000 per day by the second month of
      the crisis. The prevention of high mortality due to diarrhoeal disease epidemics
      in displaced populations relies primarily on the prompt provision of adequate
      quantities of disinfected water, basic sanitation, community outreach, and
      effective case management of ill patients. In the emergency phase, effective, low
      technology measures include bucket chlorination at untreated water sources,
      designated defaecation areas, active case-finding through community outreach, and
      oral rehydration. Relief agencies must place increased emphasis on training
      personnel in relevant skills to address major public health emergencies caused by
      population displacement.

PMID- 7646640
TI  - [The Alborg Center for the treatment of cerebral arteriovenous malformations].

PMID- 7646639
TI  - Why treatment centres failed to prevent cholera deaths among Rwandan refugees in
      Goma, Zaire.
AB  - In July, 1994, in one of the worst cholera outbreaks in recent times, an
      estimated 12,000 Rwandan refugees died in Goma in eastern Zaire. The Vibrio
      cholerae strains were resistant to tetracycline and doxycycline, the commonly
      used drugs for cholera treatment. Despite the efforts of international
      organisations, which provided medical relief by establishing treatment centres in
      Goma, mortality from the disease was much higher than expected. In the area of
      Muganga camp, which had the largest concentration of refugees and where most of
      the medical aid organisations were active, the highest reported case-fatality
      ratio for a single day was 48%. The slow rate of rehydration, inadequate use of
      oral rehydration therapy, use of inappropriate intravenous fluids, and inadequate
      experience of health workers in management of severe cholera are thought to be
      some of the factors associated with the failure to prevent so many deaths during
      the epidemic. In one of the temporary treatment centres with the worst case
      fatality record, our team showed that improvement of these factors could increase
      the odds of survival of cholera patients even in a disaster setting.

PMID- 7646641
TI  - Cardiac papillary fibroelastoma.
AB  - Papillary fibroelastomas are rare cardiac tumors, but they are the most common
      primary tumor of the heart valves. These lesions occur on any of the valves or
      endothelial surfaces of the heart and may be detected by echocardiography,
      cardiac catheterization, during open heart operation for other conditions, or at
      autopsy. Because of their potential for cerebral and coronary embolization, even
      small papillary fibroelastomas should be excised.

PMID- 7646642
TI  - Blood pressure measurement method not responsible for results of Brands et al.

PMID- 7646643
TI  - Scorpion stings and role of insulin.

PMID- 7646644
TI  - Gliclazide in the treatment of obese NIDDM patients.

PMID- 7646645
TI  - Drug users' views on general practitioners.

PMID- 7646646
TI  - Isolation and in-vitro and in-vivo characterisation of a mutant of Pseudomonas
      aeruginosa PAO1 that exhibited a reduced postantibiotic effect in response to
      imipenem.
AB  - The postantibiotic effect (PAE) is the persistent inhibition of bacterial growth
      after a brief exposure to an antibiotic. Most beta-lactams do not induce a PAE
      for Gram-negative bacteria, but PAEs have been reported for carbapenems and
      penems. This study investigated the effect of sequential doses of imipenem on the
      PAE for Pseudomonas aeruginosa and Escherichia coli cultures in a chemostat. The
      PAE for the bacterial population did not change even after six successive
      exposures to imipenem. Nevertheless, screening of colonies isolated after
      repeated drug exposure identified a single P. aeruginosa mutant whose imipenem
      PAE was shortened, although the MIC was unchanged. The PAEs for the parent and
      mutant were studied in vitro in batch culture by monitoring: (i) viable counts;
      (ii) electrical impedance of the culture medium; (iii) incorporation of
      radiolabelled N-acetyl-D-glucosamine and (iv) cell volume changes. PAEs for the
      parent and mutant were found to be significantly different by all in-vitro
      methods used. Moreover, the median cell volume in antibiotic-exposed cultures
      remained much smaller and less heterogeneous than in the control cultures, even
      though both cultures were growing at the same rate. The mutant was found to have
      a reduced expression of a 52 kDa outer membrane protein. These observations
      suggest that factors in addition to suppression of bacterial growth should be
      considered when studying the PAE. The PAEs of imipenem for the parent and mutant
      were studied in a thigh infection model in leucopenic mice. Similar PAEs were
      observed in vivo for both parent and mutant in one experiment and no PAEs for
      either organism were found in a second experiment. This study showed that
      although the PAE is a stable in-vitro phenomenon, the lack of correlation between
      the in-vitro and in-vivo results warrants caution in attributing clinical
      significance to the PAE of imipenem.

PMID- 7646647
TI  - Parkinsonism--recognition and differential diagnosis.

PMID- 7646648
TI  - Unusual trigerminal nasopharyngeal teratoma in a neonate.

PMID- 7646649
TI  - [What is the treatment of choice in acute otitis media?].

PMID- 7646650
TI  - [Management in primary health care of patients with acute somatization disorder].

PMID- 7646651
TI  - How can we improve the detection of glaucoma?

PMID- 7646652
TI  - The effect of systemic flurbiprofen on bone supporting dental implants.
AB  - This article describes a study of the efficacy of the non-steroidal anti
      inflammatory drug flurbiprofen in maintaining alveolar bone around mandibular
      root-form dental implants. The preliminary results indicate that, in appropriate
      doses, flurbiprofen may spare bone around such implants.

PMID- 7646653
TI  - Medicaid managed care: can it work for children?

PMID- 7646654
TI  - [Analgesics: use, poisonings, too much?].

PMID- 7646655
TI  - Apolipoprotein E status as a predictor of the development of Alzheimer's disease
      in memory-impaired individuals.
AB  - OBJECTIVE: The outcome of patients with mild cognitive impairment is not known,
      yet these patients present a difficult dilemma for the clinician. This study was
      designed to characterize the outcome of a group of patients with mild cognitive
      impairment and to determine whether the presence of the epsilon 4 allele on the
      apolipoprotein E gene (APOE) is a predictor of that outcome. DESIGN: A
      prospective, longitudinal inception cohort. SETTING: General community clinic.
      PARTICIPANTS: A consecutive sample of 66 patients who met criteria for a
      diagnosis of a mild cognitive impairment and who had at least one clinical
      reevaluation was identified from the Mayo Clinic Alzheimer's Disease
      Center/Alzheimer's Disease Patient Registry. INTERVENTIONS: We evaluated patients
      initially and at 12- to 18-month intervals up to 54 months using standard
      neurological and neuropsychological measures such as the Mini-Mental State
      Examination, the Dementia Rating Scale, the Wechsler Adult Intelligence Scale-
      Revised, the Wechsler Memory Scale--Revised, and the Free and Cued Selective
      Reminding Test. The APOE status of study patients was determined. MAIN OUTCOME
      MEASURE: The development of dementia as determined by the Diagnostic and
      Statistical Manual of Mental Disorders, Revised Third Edition and the National
      Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's
      Disease and Related Disorders Association criteria. RESULTS: Sixty-six
      individuals had been reevaluated once (mean of 18 months), 36 individuals twice
      (mean of 36 months), and 22 individuals on three occasions (mean of 54 months),
      with conversion rates to dementia at these intervals of 24%, 44%, and 55%,
      respectively. A multivariate Cox regression model demonstrated that possession of
      an APOE epsilon 4 allele was the strongest predictor of clinical outcome.
      CONCLUSIONS: These data suggest the following: (1) patients with mild cognitive
      impairment can be clinically defined, (2) many members of this group progress to
      Alzheimer's disease, and (3) APOE epsilon 4 allele status appears to be a strong
      predictor of clinical progression.

PMID- 7646656
TI  - Sex, alcohol and violence: a community collaborative action against striptease
      shows.
AB  - Between September 1988 and February 1989, Anyinginyi Congress, an Aboriginal
      community-controlled health organisation, facilitated a collaborative community
      action against striptease shows in public bars in Tennant Creek. This action
      resulted in changes to the guidelines of the Northern Territory Liquor Act to
      regulate striptease shows in public bars and began other processes of addressing
      alcohol related problems in the community. The composition and strategies of both
      the pro- and anti-striptease lobbies are analysed within the context of changing
      power relationships between Aboriginal and non-Aboriginal people, as epitomised
      in the growth and consolidation of Aboriginal community-controlled organisations
      in Tennant Creek. The role of the media in shaping the course and direction of
      the debates as well as the response of the Northern Territory government as the
      final arbiter in the striptease conflict are scrutinised. The use of sex to sell
      alcohol is a legitimate public health concern and community action for healthier
      public policy is an important strategy in creating supporting environments for
      health.

PMID- 7646657
TI  - Surveillance for sexually transmissible diseases in Victoria, 1983 to 1992.
AB  - Surveillance systems have been developed in Victoria to determine trends in
      sexually transmissible diseases (STDs). Notifications to the Health Department
      (including laboratory notification since May 1990) have been supplemented by data
      about strains of Neisseria gonorrhoeae and cultures for Chlamydia trachomatis
      processed by the Microbiological Diagnostic Unit, enhanced laboratory
      surveillance of syphilis, and data on genital herpes and genital warts from the
      Melbourne Sexual Health Centre. During the period under review the incidence of
      gonorrhoea declined, rapidly at first, and then more slowly. For women, this
      trend has continued, while gonorrhoea acquired abroad by men has become
      relatively more important. Since 1988, gonorrhoea in homosexual men has
      increased, and rectal isolates have increased concurrently, raising concerns
      about HIV risk behaviour. Cases of syphilis are likely to be ascertained through
      STD, antenatal and refugee screening, rather than because of symptoms or contact
      tracing. Chlamydia is a the most common notifiable STD, despite underreporting
      and underdiagnosis. In 1991, 832 cases were notified, increasing to 1377 in 1992.
      In 1992, of the 73 cases (65 per cent of notifications) where the doctor
      identified a risk, 15 per cent was attributed to homosexual contact, and 27.4 per
      cent to heterosexual exposure. Limitations in the data include inadequate
      standard case definitions for many STDs, changes in the statutory requirement for
      notifications in 1990, underreporting, changes in diagnostic and screening
      patterns, and lack of detailed demographic data. Education of general
      practitioners is needed to improve diagnosis and notification of chlamydia.

PMID- 7646658
TI  - If two's company, three may be a crowd.

PMID- 7646659
TI  - [Coronavirus infection in infants: lower respiratory tract involvement, apnea and
      sudden death?].

PMID- 7646660
TI  - [With maintaining equilibrium: experimental study of the limits of acceleration
      which the human body can endure without losing postural balance].

PMID- 7646661
TI  - Long-term survivors of human immunodeficiency virus type 1 infection.

PMID- 7646662
TI  - Acute respiratory distress syndrome.

PMID- 7646663
TI  - Regeneration of T cells after chemotherapy.

PMID- 7646664
TI  - Breast and cervical cancer screening in a low-income managed care sample: the
      efficacy of physician letters and phone calls.
AB  - A randomized trial was conducted to evaluate the combined impact of a physician
      reminder letter and a telephone contact on the use of Pap tests and mammograms in
      a low-income managed care program. Women 40 to 79 years of age who were past due
      for cancer screening were randomly assigned to an intervention or control group.
      Medical claims were reviewed after 6 months to determine intervention
      effectiveness. The odds of receiving all needed cancer screening tests during
      follow-up were four times higher in the intervention group. Women who reported
      having to take time off from work to see a doctor had lower odds of getting
      screened.

PMID- 7646665
TI  - [Holt-Oram syndrome. Review and report of 2 clinical cases in a family].

PMID- 7646667
TI  - [The treatment of the restless legs syndrome and periodic sleep movements].

PMID- 7646666
TI  - Multiple origins of anural development in ascidians inferred from rDNA sequences.
AB  - Ascidians exhibit two different modes of development. A tadpole larva is formed
      during urodele development, whereas the larval phase is modified or absent during
      anural development. Anural development is restricted to a small number of species
      in one or possibly two ascidian families and is probably derived from ancestors
      with urodele development. Anural and urodele ascidians constitute a model system
      in which to study the evolution of development, but the phylogeny of anural
      development has not been resolved. Classification based on larval characters
      suggests that anural species are monophyletic, whereas classification according
      to adult morphology suggests they are polyphyletic. In the present study, we have
      inferred the origin of anural development using rDNA sequences. The central
      region of 18S rDNA and the hypervariable D2 loop of 28S rDNA were amplified from
      the genomic DNA of anural and urodele ascidian species by the polymerase chain
      reaction and sequenced. Phylogenetic trees inferred from 18S rDNA sequences of 21
      species placed anural developers into two discrete groups corresponding to the
      Styelidae and Molgulidae, suggesting that anural development evolved
      independently in these families. Furthermore, the 18S rDNA trees inferred at
      least four independent origins of anural development in the family Molgulidae.
      Phylogenetic trees inferred from the D2 loop sequences of 13 molgulid species
      confirmed the 18S rDNA phylogeny. Anural development appears to have evolved
      rapidly because some anural species are placed as closely related sister groups
      to urodele species. The phylogeny inferred from rDNA sequences is consistent with
      molgulid systematics according to adult morphology and supports the polyphyletic
      origin of anural development in ascidians.

PMID- 7646668
TI  - [Resistant tuberculosis and meningitis].

PMID- 7646669
TI  - Antioxidants in IVF culture media.

PMID- 7646670
TI  - Avoiding unsuspected respiratory side-effects of topical timolol with
      cardioselective or sympathomimetic agents.
AB  - Topical timolol given for the treatment or chronic simple glaucoma may cause
      unrecognised bronchospasm among elderly people. We recruited 80 patients aged
      over 60 years, who were without a history of airways disease and already used
      timolol, into a randomised crossover study comparing the effects on spirometry
      and exercise tolerance of changing to betaxolol or dipivefrine therapy. Results
      showed an increase of 13% and 8% in mean peak flow rate and forced expiratory
      volume in 1 s (FEV1), respectively, when using betaxolol; and of 14% and 11% when
      using dipivefrine. There was also improved exercise tolerance with both agents.
      More than a quarter of the patients showed at least a 15% improvement in FEV1
      when changed from timolol. Analysis of enrolment symptoms and response to
      nebulised salbutamol failed to produce a method of identifying these patients.
      Timolol may impair respiratory function and exercise tolerance of elderly
      patients even if they have no history of reversible airways disease.

PMID- 7646671
TI  - New rules on medicines.

PMID- 7646672
TI  - Uptake of breast screening by Asian women.

PMID- 7646673
TI  - Are genital herpes and warts really disappearing problems?

PMID- 7646674
TI  - Services for cleft lip and palate. Maxillofacial surgeons use strict surgical
      protocol.

PMID- 7646675
TI  - Nicotine patches.

PMID- 7646676
TI  - Rationing intensive care. Intensive care provision varies widely in Britain.

PMID- 7646677
TI  - Comparison of SVO2, SPO2, and clinical parameters with arterial blood gases
      during ventilatory weaning after cardiac surgery.

PMID- 7646678
TI  - Tourette's syndrome and psychiatric disorders.

PMID- 7646679
TI  - Wegener's granulomatosis and CREST syndrome--Le Thi Huong D, Gatfosse M et al.

PMID- 7646680
TI  - Rhinestones and gold-dust: attention deficit, borderline personality, or mood
      disorder?

PMID- 7646681
TI  - Parental presence at induction.

PMID- 7646682
TI  - The predictive value of a single serum level of human chorionic gonadotropin for
      pregnancy outcome.

PMID- 7646683
TI  - Repeat laser therapy of recurrent Barrett's epithelium: success with anacidity.

PMID- 7646684
TI  - A question-filled future for dose-escalation in prostate cancer--regarding
      Shipley et al., IJROBP 32:3-12; 1995.

PMID- 7646685
TI  - Praise for guidelines.

PMID- 7646686
TI  - A preliminary single case magnetic resonance imaging investigation into maxillary
      frontal-parietal manipulation and its short-term effect upon the intercranial
      structures of an adult human brain.

PMID- 7646687
TI  - Cholera treatment in Goma.

PMID- 7646688
TI  - Thyrotropin-releasing hormone for prevention of neonatal respiratory disease.

PMID- 7646689
TI  - Acupuncture technique.

PMID- 7646690
TI  - Interleukin-2 as therapy for HIV disease.

PMID- 7646691
TI  - Health care reform in the United States.

PMID- 7646692
TI  - Interval cytoreduction in ovarian cancer.

PMID- 7646693
TI  - Patients with chronic diarrhea.

PMID- 7646694
TI  - Metaphors and health care reform.

PMID- 7646695
TI  - Fluconazole in candida peritonitis in CAPD: an alternative proposal.

PMID- 7646696
TI  - [Cardiovascular changes associated with the use of acrylic bone cement].

PMID- 7646697
TI  - Gleason grading.

PMID- 7646698
TI  - Should acidosis during liver transplantation be treated?

PMID- 7646699
TI  - Chest pain treatment center.

PMID- 7646700
TI  - Re: Scrotal construction by expansion of labia majora in biological female
      transsexuals.

PMID- 7646701
TI  - Has the cost-effectiveness of misoprostol been underestimated?

PMID- 7646702
TI  - JNC V neither limited nor guided by economics.

PMID- 7646703
TI  - Amyloidosis secondary to xanthogranulomatous pyelonephritis: an unusual case.

PMID- 7646704
TI  - The role of pipelle endometrial biopsy in patients with postmenopausal bleeding.

PMID- 7646705
TI  - Plasma interferon alpha and the wasting syndrome in patients infected with the
      human immunodeficiency virus.

PMID- 7646706
TI  - Improving the detection of glaucoma. Link between glaucoma and diabetes is
      disputed.

PMID- 7646707
TI  - Professional negligence. Negligence cannot be decided by offending doctor.

PMID- 7646708
TI  - Unified training grade. Expanding consultant numbers is not enough.

PMID- 7646710
TI  - Randomized trial of modified Bassini versus Shouldice inguinal hernia repair.

PMID- 7646709
TI  - Treatment of mycoplasma contamination.

PMID- 7646711
TI  - Gastric motility and gastric emptying.

PMID- 7646712
TI  - The concept of balanced autonomy in therapeutic and nontherapeutic trials.

PMID- 7646713
TI  - Age-standardization in epidemiological data.

PMID- 7646714
TI  - Arteriovenous malformation of the mandible.

PMID- 7646715
TI  - Medical applications on the Internet.

PMID- 7646716
TI  - Clearance of HIV in an infant.

PMID- 7646717
TI  - Supraventricular tachycardia.

PMID- 7646718
TI  - A philosopher's point of view.

PMID- 7646719
TI  - Single odorant molecules?

PMID- 7646720
TI  - Snake bites.

PMID- 7646721
TI  - Re: "Can energy adjustment separate the effects of energy from those of specific
      macronutrients?".

PMID- 7646722
TI  - Surgical revascularization for left main coronary artery atresia.

PMID- 7646723
TI  - Bacterial contamination of enteral feeding reservoirs.

PMID- 7646724
TI  - Viral illness and chronic fatigue (syndrome)

PMID- 7646725
TI  - Outcome of transplantation of non-heart-beating donor kidneys.

PMID- 7646726
TI  - Streptokinase in acute ischaemic stroke. Steering Committees of the ASK and MAST
      E trials. Australian Streptokinase Trial.

PMID- 7646727
TI  - Ruptured breast implant.

PMID- 7646728
TI  - Some ethical issues surrounding covert video surveillance--a response.
AB  - In a recent article in this journal our unit was accused of a number of errors of
      judgment in applying covert video surveillance (CVS) to infants and children
      suspected of life-threatening abuse. The article implied, that on moving from the
      Royal Brompton Hospital in London to North Staffordshire Hospital, we failed to
      present our work to the Research Ethics Committee (REC). We did send our protocol
      to the REC though we did not consider that, after a total of 16 patients had been
      documented as being the subject of life-threatening abuse, this was research. The
      REC in Staffordshire agreed with us. We were also accused of undertaking work
      that should be pursued by the Police. We agree with this. However, unlike the
      Metropolitan Police the Staffordshire Police would not undertake CVS. We fail to
      agree that 'working together' with parents is necessarily practical or safe when
      trying to protect children from life-threatening abuse of this kind.

PMID- 7646729
TI  - Events per person year. Use individual event rate adjustment for follow up time.

PMID- 7646730
TI  - ABC of medical computing. Choosing a computer system.

PMID- 7646731
TI  - Genetic testing for familial hypertrophic cardiomyopathy in newborn infants. A
      positive screening test for an untreatable condition provides psychological
      relief from uncertainty.

PMID- 7646732
TI  - [The long-term follow-up of the smoker who has had minimal intervention for
      smoking].

PMID- 7646733
TI  - Beyond medical error.

PMID- 7646734
TI  - Students' learning styles do affect performance.

PMID- 7646735
TI  - Not everybody likes problem-based learning in a clerkship.

PMID- 7646736
TI  - Teaching awareness of cognitive bias in medical decision making.

PMID- 7646737
TI  - Time to put managed care into medical and public health education.

PMID- 7646738
TI  - Teaching an integrated approach to health care: lessons from five schools.
AB  - Medical education has excelled in bringing a sound biomedical base to the
      practice of medicine; however, there is now growing interest in helping students
      and residents learn an integrated approach to health care that addresses the
      complex interaction of many factors influencing health and illness. The authors'
      purpose was to learn about how some medical schools teach students a more
      integrated approach to health care. They used a qualitative, multiple-case-study
      design and collected data through document review and interviews with faculty,
      administrators, students, and residents at five U.S. and Canadian medical
      schools, chosen for their reputed excellence in addressing an integrated approach
      to care. Visits to the schools were made in the spring of 1993. Data analysis
      focussed on the institutional factors associated with teaching such an approach
      and the ways in which the schools help students and residents learn about this
      approach. The interviewees described the strong presence of an institutional
      mission or philosophy that is unique to each school but that generally has a
      service-oriented, patient-centered perspective. They reported that the primary
      means for learning about an integrated approach was the attention, woven into the
      curriculum, to four relationships; physician-patient, physician-community,
      physician-other practitioners, and faculty-student. A broad-based shared mission
      or philosophy was important in focusing attention on the integration of
      biomedical and non-biomedical concerns and promoting a perspective that focuses
      outward toward the community and its people. The pervasive attention to the four
      relationships suggests that such attention is intimately related to each school's
      underlying mission or philosophy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7646739
TI  - The undergraduate medical curriculum: centralized versus departmentalized.
AB  - The authors describe the advantages and disadvantages of central governance of
      the undergraduate medical curriculum as contrasted with traditional departmental
      approaches, based upon their school's experience with a new centrally governed
      curriculum during the preceding four years. Central governance has more
      advantages, but also more costs, compared with traditional departmental
      approaches. Central governance does what it was intended to do: it provides
      rational and integrative mechanisms for ensuring a broad general education in
      medicine focusing on the doctor-patient relationship. It also provides an
      effective mechanism for dealing with "turf" and time issues in the curriculum
      while allowing for and encouraging changes and providing mechanisms for
      evaluating those changes. However, as the allocation of resources and rewards
      remains more departmentally than centrally based, a major challenge of central
      governance has been to help faculty resolve a "conflict of loyalty" (the sense of
      serving two masters) between school and department, particularly in the
      evaluation and reward of teaching. On balance, central governance provides a
      powerful means of introducing broad-based reforms into all elements of the
      undergraduate medical curriculum, but it requires ongoing collaboration with
      faculty and chairs to assist them in negotiating competing pressures and
      priorities as they strive to become excellent teachers.

PMID- 7646740
TI  - Rethinking our basic concepts of health and disease.
AB  - Medical students' concerns that their education is not preparing them to be the
      doctors they could be can be traced in part to inadequacies in the basic concepts
      of health and disease they are taught, which prevent them from learning how to
      most effectively meet the challenges and exigencies of patient care. The author
      proposes an alternative theoretical perspective on the biological foundations of
      medicine by describing two divergent models of health and disease. The first,
      reductive isolation, represents the dominant theoretical approach to health and
      disease in contemporary medical education and practice. It emphasizes
      quantification and measurement and aims to peer beneath variability,
      subjectivity, and the infinite variety of patients' experiences to something
      universally definable, measurable, and objective. The second model, ascendant
      interrelation, takes as its starting point a special and prototypical property of
      the living organism, metabolism, in which the organism has an identity that
      transcends the material of which it is made, and in which such characteristics as
      form, wholeness, self-generation, and integration dominate. Medicine and the
      teaching of medicine must use both these models; the tools of reductive isolation
      are necessary but must be applied with a view to the larger and more complex
      reality of the patient as addressed by ascendant interrelation. Alone, reductive
      isolation does not offer an adequate perspective on the health of the whole human
      being, just as the well-functioning of the eye cannot be adequately explained
      without reference to seeing. In short, patients are more than their diseases;
      complex factors in their lives must not be overlooked as contributors to their
      illnesses or keys to healing.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7646741
TI  - Exit rounds: a reflection exercise.
AB  - This paper questions the long-held assumption that "experience is the best
      teacher". Reflection, it is argued, is the element that turns experience into
      learning. Unfortunately, reflection is the experiential learning skill in which
      student are most deficient. Further, clinical teachers may not appreciate the
      reciprocal and synergistic relationship of experience and reflection, and
      therefore they may not exploit its full potential. This paper argues for the
      formal and explicit use of reflection to clinical teaching. In addition to
      providing a theoretical rationale for the use of reflection is learning, one
      example of a reflection exercise--exit rounds--is described. Exit rounds focus on
      recently discharged patients and provide students with an opportunity to reflect
      on what they have learned from working with these patients. In addition to being
      a learning exercise, exit rounds provide attending physicians with an opportunity
      to address emotional issues, to evaluate students' learning and performances, to
      deal with "housekeeping" details, and to provide closure.

PMID- 7646742
TI  - Numbers of physicians and medical students in Europe and the United States.
AB  - The authors compared data from the early 1990s for physicians and medical
      students in the United States with data for those in 14 members of the European
      Union and 15 other European countries within the European region as defined by
      the World Health Organization. With a total population twice that of the United
      States, the European countries had three times the numbers of physicians and
      first-year students, and five and one-half times the number of applicants to
      medical schools. Europe has a higher density of physicians (an average of one
      physician for every 335 people) than the United States (one physician for every
      472 people). Numbers of medical schools per million people are similar (1.8
      versus 2.0), but the average first-year class size is larger in Europe (184
      versus 136 students). There is approximately on first-year medical student per
      10,000 people in Europe, compared with one per 15,000 people in the United
      States. It is likely that these ratios will remain the same, since both the
      United States and Europe have approximately one first-year medical student for
      every 30 practicing physicians, and the student admission policies of the
      individual countries appear to mirror the physician-population ratios. There is
      one applicant for every 2,125 people in Europe; the United States has one
      applicant for every 5,174 people. Further, Europe has 4.6 applicants for every
      place in the class, while the United States has 2.6. Finally, the authors provide
      detailed information about physicians and students in the countries surveyed.

PMID- 7646743
TI  - Histories of academic medical education.
AB  - The author discusses the ways in which the history of medicine has changed in
      recent times, from an emphasis on celebrating past events to a focus on
      elucidating the nature of changes in medical care. Characteristic historical
      methodologies are described, including a tendency to use multiple types of
      sources. The importance of education in medical history and the potential utility
      of the study of history for contemporary medical practice are emphasized. The
      author gives examples of the many ways in which the history of medical education
      might be conceptualized.

PMID- 7646744
TI  - Educating physicians in cyberspace.

PMID- 7646745
TI  - The future of veterans' health care.

PMID- 7646746
TI  - Ambulatory medical education: teachers' activities, teaching cost, and residents'
      satisfaction.
AB  - PURPOSE: To assess faculty activities and costs in supervising ambulatory patient
      care at a family practice clinic, and to assess resident satisfaction with access
      to ambulatory care teaching. METHOD: This time-and-motion study was conducted in
      1993 over two three-week periods (at the end of one academic year and at the
      beginning of another) in a family practice clinic affiliated with the University
      of Iowa College of Medicine. Observers recorded time spent by 14 faculty on
      teaching and non-teaching activities. Thirty-two residents were surveyed about
      their satisfaction with access to teaching. RESULTS: Over 59 half-days, 2,644
      faculty service events were recorded; 47% were teaching events (supervising care
      delivered by residents) and 53% were non-teaching events (providing care for
      other clinic patients). Mean teaching time was greater for first-year residents;
      they consulted faculty more frequently and required more teaching time per
      consultation. The most common non-teaching activities were telephone calls out,
      telephone calls in, and inquiries from nurses and office staff. Ten percent of
      non-teaching activities interrupted teaching, and 17% of the residents reported
      their teaching had been interrupted. Eighty percent of the residents were
      satisfied with their access to teaching, but 12% reported they had had to
      postpone discussing pressing patient problems. Resident dissatisfaction
      correlated with longer perceived waiting time, interruption of teaching, and
      faculty inaccessibility. CONCLUSION: Faculty should plan to spend two to three
      times longer to teach lower-level residents than upper-level residents. By
      delegating some non-teaching activities to other personnel, faculty can reduce
      teaching costs and increase resident satisfaction.

PMID- 7646747
TI  - What makes a tutor effective? A structural-equations modeling approach to
      learning in problem-based curricula.
AB  - PURPOSE: To test and further develop a causal model of the influence of tutor
      behaviors on student achievement and interest in the context of problem-based
      learning. METHOD: Data from 524 tutorial groups involving students participating
      in the four-year undergraduate health sciences curriculum at the University of
      Limburg in 1992-93 were analyzed. The tutorial groups were guided by 261 tutors.
      Overall, 3,792 data records were studied, with each student participating in an
      average of 2.3 groups. Correlations among tutors' social-congruence, expertise
      use, and cognitive-congruence behaviors, small-group functioning, and student'
      self-study time, intrinsic interest in subject matter, and level of achievement
      were analyzed using structural-equations modeling. This statistical technique
      allows the investigator to test causal hypotheses on correlational data by
      comparing the structure of data with a theoretical model. RESULTS: After minor
      adaptations, the hypothesized causal model of the effective tutor fitted the data
      extremely will. Each tutor's level of expertise use and social congruence not
      only directly affected his or her level of cognitive congruence but also affected
      other elements of the model. Level of social congruence influenced group
      functioning in a direct fashion, while expertise use had a slightly negative
      effect on the students' level of self-study time and a slightly positive effect
      on level of achievement. As hypothesized, the level of cognitive congruence
      influenced tutorial-group functioning. Level of group functioning affected self
      study time and intrinsic interest. Finally, time spent on self-study influenced
      level of achievement. CONCLUSION: The results suggest that subject-matter
      expertise; a commitment to students' learning and their lives in a personal,
      authentic way; and the ability to express oneself in the language used by the
      student are all determinants of learning in problem-based curricula. The theory
      of the effective tutor, presented in this article, merges two different
      perspectives prevalent in the literature. One perspective emphasizes the personal
      qualities of the tutor: his or her ability to communicate with students in an
      informal way, coupled with an empathic attitude that enables the tutor to
      encourage student learning by creating an atmosphere in which open exchange of
      ideas is facilitated. The other stresses the tutor's subject-matter knowledge as
      a determinant of learning. The data presented in this article suggest that what
      is needed, really, is much of both.

PMID- 7646748
TI  - Students' general learning approaches and performances in medical school: a
      longitudinal study.
AB  - PURPOSE: To examine the relationship between students' learning approaches and
      performances in a baccalaureate--MD degree program over six years, from
      orientation to the final year. METHOD: At the University of Missouri-Kansas City
      School of Medicine, the short-form Lancaster Approaches to Studying Inventory was
      administered to the matriculating classes of 1988 (100 students) and 1989 (102
      students) at the beginning of the first and second semesters of years 1 and 2 and
      during the first semester of years 3 through 6 for the class of 1988 and years 3
      through 5 for the class of 1989. Seven learning-approaches dimensions from the
      inventory were regressed against 16 academic and clinical performance measures.
      RESULTS: As anticipated, a consistent predictive pattern emerged. Students who
      scored high on achievement motivation (efficient study habits and an extrinsic
      need to succeed) but who scored low on reproducing orientation (rote memory) and
      globetrotting (a fragmented approach to studying) achieved higher grade-point
      averages in years 1, 2, and 4 than did their counterparts who scored low on
      achievement motivation and high on reproducing orientation and globetrotting. The
      utility of the remaining learning-approaches dimensions for performances in
      specific courses and clinical rotations varied. The data also indicated that the
      initial level of students' learning approaches is an important qualifier of the
      predictive capability of the dimensions for students' performances. CONCLUSIONS:
      The results prompted a revised model of how learning approaches relate to
      performance. The model incorporates students' initial scores on learning
      approaches as an element that influences students' perceptions of the educational
      context. In turn these perceptions have an impact on students' selections of
      learning approaches that are associated with performance.

PMID- 7646749
TI  - The role of career pathway before medical school in graduates' choice of primary
      care versus other specialty practices.
AB  - PURPOSE: To analyze the difference, if any, in the choices of primary care versus
      other specialty practices among graduates of the Albany Medical College who took
      one of three career pathways before entering medical school and who had entered
      primary care residencies. METHOD: Questionnaires were mailed in April 1992 to all
      458 graduates from the classes of 1980 through 1985 who had entered primary care
      residencies (i.e., residencies in family practice, general internal medicine,
      general pediatrics, or medicine--pediatrics). The graduates had followed one of
      three pathways to admission: (1) after completion of four years of college, (2)
      after completion of the six-year biomedical program in conjunction with the
      Rensselaer Polytechnic Institute (RPI), and (3) after having pursued a nonmedical
      career and being older than 25 years of age. Logistics regression was the primary
      vehicle for analysis, defining career choice as the dependent variable and using
      the independent variables of sex, year of graduation, and pathway as well as
      their interactions for a saturated-model analysis. RESULTS: A total of 318
      graduates (69%) responded. Among the three pathways, there was no statistically
      significant difference in the choices of primary care versus other specialty
      practices. However, in the RPI and age-greater-than-25 groups, there was a
      greater tendency for men to choose other specialties. CONCLUSIONS: The three
      career pathways before medical school did not appear to have a role in the choice
      of primary care versus other specialty practices among graduates who had entered
      primary care residencies. However, gender did influence this choice.

PMID- 7646750
TI  - STD risk assessment and risk-reduction counseling by recently trained family
      physicians.
AB  - PURPOSE: To survey recently trained family physicians about their practices and
      perceptions regarding sexual history taking, drug-use history taking, and safe
      sex counseling. METHOD: The study was conducted with all 1991 graduates from the
      four family practice residency programs in Quebec, Canada. Data were collected in
      1992 by using a mailed questionnaire. RESULTS: A total of 148 (80%) of the 186
      contacted physicians responded. The physicians reported taking a sexual history
      less frequently than a drug-use history when seeing patients for a general
      medical examination (42% versus 71%) or a first pregnancy visit (75% versus 91%).
      When taken, the sexual history was often too superficial to detect risk
      behaviors. Consequently, safe-sex counseling was infrequent. Over 20% of the
      physicians worried about patients' discomfort, were uneasy discussing sexual
      matters, and did not feel properly trained in sexual history taking. Graduates
      from the family practice residency at the school that offered training in human
      sexuality performed better sexual history taking than did graduates from the
      residencies at the other schools. CONCLUSIONS: Although infections from sexually
      transmitted diseases and the human immunodeficiency virus are important causes of
      morbidity and mortality, family physicians are still not actively involved in
      their prevention. The study suggests that medical education might be deficient in
      this area and that more training in human sexuality should be provided for family
      physicians.

PMID- 7646751
TI  - A strategy for improving patient satisfaction by the intensive training of
      residents in psychosocial medicine: a controlled, randomized study.
AB  - PURPOSE: To use a controlled, randomized design to assess the effect on patient
      satisfaction of an intensive psychosocial training program for residents. METHOD:
      Twenty-six first-year residents, in two internal medicine and family practice
      community-based programs affiliated with the Michigan State University College of
      Human Medicine, were randomly assigned during 1991 and 1992 to a control group or
      a one-month intensive training program. Experiential teaching focused on many
      psychosocial skills required in primary care. A 29-item questionnaire
      administered before and after the residents' training evaluated their patients'
      satisfaction regarding patient disclosure, physician empathy, confidence in
      physician, general satisfaction, and comparison of the physician with other
      physicians. Analyses of covariance with groups and gender as factors and pre
      training patient satisfaction scores as the covariate evaluated the effect of the
      training. RESULTS: The patients of the trained residents expressed more
      confidence in their physicians (p = .01) and more general satisfaction (p = .02)
      than did the patients of controls. The effect of training on patient satisfaction
      with patient disclosure (p < .01) and physician empathy (p < .05) was greater for
      female than for male residents. CONCLUSION: The intensive psychosocial training
      program for residents improved their patients' satisfaction.

PMID- 7646752
TI  - Investigating the development of self-evaluation skills in a problem-based
      tutorial course.
AB  - PURPOSE: To compare students' self-evaluations of their performances with the
      evaluations they received from their tutors in a problem-based course. METHOD: In
      the Occupational Therapy and Physiotherapy Programme of the McMaster University
      Faculty of Health Sciences in 1993-94, a study was conducted of the self
      evaluation skills of 30 students in five tutorial groups. Repeated-measures
      analyses of variance, factor analyses, and Pearson correlations were used to
      examine the student's self-evaluations in comparison with their tutors'
      evaluations on six consecutive occasions over a 14-week period. RESULTS:
      Significant (p < .01) increases were found for both students' and tutors'
      evaluation scores over the six evaluations. A significant interaction was also
      found, with the tutors' evaluations being initially lower but eventually higher
      than the students' self-evaluations. Correlations between students' and tutors'
      evaluations rose in a sawtooth manner from .49 on the first evaluation to .84 by
      the sixth evaluation. There was a pattern of diminishing oscillations in the
      interobserver correlations over the six evaluations. CONCLUSION: When combined
      with the steady increase in evaluation scores, the pattern of diminishing
      oscillations in interobserver correlations was interpreted more as evidence of a
      negotiation process between students and their tutors than as evidence of
      improvement in self-evaluation skills.

PMID- 7646754
TI  - Products and services: wound care.

PMID- 7646753
TI  - Use of live animals in the curricula of U.S. medical schools in 1994.
AB  - In 1994, the AAMC surveyed the 126 U.S. medical schools to obtain data on live
      animal use in the undergraduate medical curriculum. The questions focused
      entirely on the use of live animals in teaching laboratories that are either
      required or optional parts of the undergraduate medical curriculum. Seventy-seven
      of the 125 responding schools used live animals in one or more courses; of the
      required courses, animals were most often used in physiology courses (49
      schools), followed by surgical clerkships (21) and pharmacology courses (13).
      Although these data show that the majority of schools used live animals in their
      curricula, the data also show that the majority of schools did not use live
      animals as part of the teaching of any specific course of discipline in 1994. The
      animals most often used were dogs (54 schools) and pigs (12). Forty-three of the
      77 schools that used live animals offered a variety of alternatives to their use.
      The respondents' data indicate a steady decline in the number of schools using
      live animals in teaching labs since before 1982. The reasons most often reported
      for discontinuing live-animal use were expense, changes in curriculum or
      curriculum focus, and lack of time, faculty, or space. Several other reasons were
      also listed, but live animals' value in teaching was seldom a factor. Only 15
      schools indicated they had experienced harassment, protests, or legal actions
      arising from their use of live animals in the previous two years.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7646755
TI  - Products and services: continence/incontinence.

PMID- 7646756
TI  - Products and services: ostomy care.

PMID- 7646757
TI  - Products and services: support surfaces.

PMID- 7646758
TI  - Ninth Aspen Cancer Conference: mechanisms of toxicity and carcinogenesis.

PMID- 7646759
TI  - Low frequency of CDKN2 mutation in endometrial carcinomas.
AB  - The CDKN2 gene on chromosome 9p21 encodes the p16 inhibitor of cyclin D/cyclin
      dependent kinase 4 complexes. Mutations and deletions of CDKN2 have been
      frequently identified in cell lines, whereas most primary tumors have
      demonstrated a lower frequency of alteration. To assess the role of CDKN2 in
      endometrial tumorigenesis, 34 tumor samples were examined for loss of
      heterozygosity at 9p21 and mutation in CDKN2. To identify tumors that had lost
      9p21, samples were genotyped with markers flanking the CDKN2 locus. The frequency
      of CDKN2 mutation in endometrial carcinomas was determined by single-strand
      conformation variant analysis and direct sequencing of variants. Of the 34 tumors
      examined, three revealed loss of 9p21 sequences. Two samples were characterized
      by point mutations in CDKN2, one of which also showed loss of 9p21 sequences.

PMID- 7646760
TI  - How are potent bulky carcinogens able to induce such a diverse array of
      mutations?
AB  - Mutations induced by activated benzo[a]pyrene ((+)-anti-B[a]PDE) in Escherichia
      coli are being investigated, by using both random and adduct-site-specific
      mutagenesis approaches. A working hypothesis was proposed that the major adduct
      of (+)-anti-B[a]PDE (formed at N2-Gua) is able to induce different base
      substitution mutations (e.g., GC-->TA vs. GC-->AT) depending upon its
      conformation in DNA, which can be influenced by various factors, notably DNA
      sequence context. Frameshift mutations are also common with (+)-anti-B[a]PDE, and
      other work suggested that the frameshift and base-substitution mutagenesis
      pathways are coupled. The simplest hypothesis to rationalize this
      interrelationship is that a single (+)-anti-B[a]PDE adduct in a single
      conformation can be bypassed via either a frameshift or a base-substitution
      pathway. This counterintuitive notion can be reconciled if there are two
      different kinds of conformations on the pathway to mutagenesis: a class I
      conformation, which is the initial conformation of a DNA adduct in double
      stranded DNA before its encounter with a DNA polymerase, and a class II
      conformation, which is the conformation that forms at a single-strand/double
      strand DNA junction during replication by a DNA polymerase. Thus, GC-->TA and GC-
      >AT mutations may be induced by different class I conformations, whereas base
      substitution and frameshift mutations may be induced by the same class I
      conformation but by different class II conformations. The pathway of mutagenesis
      would be dictated by the relevant class I and II conformations, which in turn
      would be controlled by various factors, notably DNA sequence context.

PMID- 7646761
TI  - Suppression of the tumorigenic phenotype of a rat liver epithelial tumor cell
      line by the p11.2-p12 region of human chromosome 11.
AB  - Comparative chromosomal mapping studies and investigations of tumor-associated
      chromosomal abnormalities suggest that the development of hepatic tumors in
      humans and rats may share a common molecular mechanism that involves inactivation
      of the same tumor suppressor genes or common genetic loci. We investigated the
      potential of human chromosomes 2 and 11 to suppress the tumorigenic phenotype of
      rat liver epithelial tumor cell lines. These tumor cell lines (GN6TF and GP7TB)
      display elevated saturation densities in culture, efficiently form colonies in
      soft agar, and produce subcutaneous tumors in 100% of syngeneic rat hosts with
      short latency periods. Introduction of human chromosome 11 by microcell fusion
      markedly altered the tumorigenicity and the transformed phenotype of GN6TF cells.
      In contrast, the tumorigenic potential and phenotype of GP7TB cells was
      unaffected by the introduction of human chromosome 11, indicating that not all
      rat liver tumor cell lines can be suppressed by loci carried on this chromosome.
      Introduction of human chromosome 2 had little or no effect on the tumorigenicity
      or cellular phenotype of either tumor cell line, suggesting the involvement of
      chromosome 11-specific loci in the suppression of the GN6TF tumor cell line. The
      GN6TF-11neo microcell hybrid cell lines displayed significantly reduced
      saturation densities in monolayer cultures, and their ability to grow in soft
      agar was completely inhibited. Although GN6TF-11neo cells ultimately formed
      tumors in 80-100% of syngeneic rat hosts, the latency period for tumor formation
      was much longer. Molecular characterization of GN6TF-11neo microcell hybrid cell
      lines indicated that some of the clonal lines had spontaneously lost significant
      portions of the introduced human chromosome, partially delineating the
      chromosomal location of the putative tumor suppressor locus to the region between
      the centromere and 11p12. Molecular examination of microcell hybrid-derived tumor
      cell lines further defined the minimal portion of human chromosome 11 capable of
      tumor suppression in this model system to the region 11p11.2-p12.

PMID- 7646762
TI  - Investigation of the cooperative effects of transforming growth factor alpha and
      c-myc overexpression in rat liver epithelial cells.
AB  - Overexpression of both transforming growth factor (TGF)-alpha and c-myc is
      consistently reported in hepatic tumors. We transfected rat liver epithelial
      cells (RLECs) with expression vectors for TGF-alpha, c-myc, or both and analyzed
      the morphology, biological properties, and tumorigenicity of clones that
      overexpressed these genes. The transfectants were morphologically
      indistinguishable from the parental RLECs, but the overexpression of TGF-alpha
      resulted in changes in growth properties and an enhanced response to the
      mitogenic effects of hepatocyte growth factor. The concomitant overexpression of
      c-myc decreased growth factor requirements of the TGF-alpha lc-myc clones
      compared with RLEC and TGF-alpha clones. The TGF-alpha and TGF-alpha lc-myc
      clones were tumorigenic in nude mice at frequencies of 27% and 53%, respectively,
      indicating that the genes cooperate in malignant transformation. However, the
      untransformed nature and low tumorigenicity of the transfectants suggest that
      transformation depends on other cellular events in addition to the overexpression
      of TGF-alpha or c-myc. Characterization of tumor cell lines showed that in
      contrast to the transfectants, the tumor clones were morphologically transformed,
      capable of autonomous growth and anchorage-independent growth, and aggressively
      tumorigenic with a frequency of 100%. Clearly, the tumor cells differed from the
      transfectants and had undergone biological or genetic alterations (or both) as a
      consequence of the overexpression of TGF-alpha or c-myc. Our data suggest that
      the overexpression of TGF-alpha leads to enhanced responsiveness to hepatocyte
      growth factor, whereas the concomitant overexpression of c-myc confers growth
      factor independence, providing a potential explanation of the mechanisms by which
      the overexpression of these genes results in transformation.

PMID- 7646763
TI  - A human factor that recognizes DNA substituted with 2-chloroadenine, an
      antileukemic purine analog.
AB  - 2-Chloro-2'-deoxyadenosine (cladribine), an analog of deoxyadenosine, is an
      important new drug for the treatment of hairy cell leukemia and other forms of
      adult and pediatric leukemia. By a gel-shift binding assay, we identified an
      activity in HeLa nuclear extracts that recognizes and binds to oligonucleotides
      substituted with 2-chloroadenine (ClAde). The activity was specific for ClAde
      residues because control oligomers did not readily compete out the complex. The
      binding factor was a monomeric protein that was resistant to inactivation by
      heating at 45 degrees C but sensitive to heating at 65 degrees C, proteinase K
      treatment, and 5 mM ZnCl2. This protein, designated ClAde recognition protein
      (CARP), appeared to be related to a protein that recognized other forms of DNA
      damage. Gel-shift binding reactions with ultraviolet (UV)-irradiated oligomers
      revealed a UV-specific protein/DNA complex that had an electrophoretic mobility
      similar to that of the CARP/DNA complex, and CARP binding to ClAde-containing
      oligomers was readily competed out by UV-irradiated DNA. Moreover, CARP activity
      was present in extracts prepared from UV-sensitive xeroderma pigmentosum group A
      cells but not in a subset of cells from group E, suggesting that CARP was similar
      to a previously described repair associated factor, xeroderma pigmentosum-E
      binding factor. Our findings support a possible repair process for ClAde residues
      incorporated into cellular DNA.

PMID- 7646764
TI  - Cellular immortality: a late event in the progression of human squamous cell
      carcinoma of the head and neck associated with p53 alteration and a high
      frequency of allele loss.
AB  - Many human tumors contain variant cells that, unlike their normal counterparts,
      possess indefinite proliferative potential in vitro. However, little is known of
      the relevance of these immortal cells to human carcinomas in vivo. To investigate
      immortality in a human tumor system, we established cultures from different
      stages of head and neck squamous carcinoma (SCC-HN). All the neoplastic cultures
      were transformed because they showed very low cornification in surface or
      suspension culture and were partially or completely resistant to suspension
      induced death. Immortal variants were not detected in premalignant erythroplakia
      cultures, but their frequency increased with tumor progression, indicating that
      immortality is a late event in carcinogenesis. Some late-stage carcinomas still
      produced senescent cultures, but, significantly, all recurrent tumors were
      immortal. Immortal but not senescent carcinoma cultures were associated with p53
      dysfunction and a high frequency of allele loss, indicative of tumor suppressor
      gene inactivation. These results show that there are at least two classes of
      human SCC-HN that are phenotypically and genotypically distinct and that the
      pathological stage of a given tumor is not necessarily indicative of the kind of
      cells it contains.

PMID- 7646765
TI  - p53 mutation without allelic loss and absence of mdm-2 amplification in a
      transplantable hamster pancreatic ductal adenocarcinoma and derived cell lines
      but not primary ductal adenocarcinomas in hamsters.
AB  - An investigation of p53 gene mutation by single-stranded conformation
      polymorphism analysis of polymerase chain reaction products followed by direct
      sequencing and of murine double minute 2 (mdm-2) gene amplification by Southern
      blot analysis was performed, using a series of hamster pancreatic duct
      adenocarcinomas: 18 primary adenocarcinomas induced by N-nitrosobis(2
      oxopropyl)amine, a transplantable adenocarcinoma (HPD), and three cell lines
      derived from HPD (HPD1NR, HPD2NR, and HPD3NR). A mutation in the p53 gene was
      detected at codon 197, resulting in an amino acid change from leucine to
      phenylalanine, in both HPD and the three cell lines but in none of the 18 primary
      adenocarcinomas. In the three HPD cell lines, which were confirmed to contain
      only cancer cells, a normal p53 gene allele was retained. Immunohistochemical
      investigation of p53 expression using polyclonal antibody Ab-7 revealed positive
      nuclear staining in the HPD and two back-transplanted tumors derived from HPD1NR
      and HPD2NR but not in the 18 primary adenocarcinomas. mdm-2 gene amplification
      was not detected in 18 primary adenocarcinomas or any of the tumor cell lines.
      The results suggest that a p53 gene mutation without allelic loss, together with
      overexpression of p53 protein, may be a genetic alteration involved in the
      progression stage of multistep pancreatic carcinogenesis in hamsters and that mdm
      2 gene amplification is not important for this process.

PMID- 7646766
TI  - Chymotrypsin-galactose treatment of sperm with antisperm antibodies results in
      improved pregnancy rates following in vitro fertilization.
AB  - PROBLEM: To determine if chymotrypsin-galactose (CG) treatment of sperm bound
      with antisperm antibodies (ASA) improves pregnancy rates (PRs) following in vitro
      fertilization (IVF). METHOD: Patients with > 50% ASA who failed to conceive
      despite six intrauterine insemination (IUI) cycles were included. Initially the
      sperm treatments were randomized with CG vs culture medium; subsequently only CG
      treatment was used. RESULTS: There was a significantly lower fertilization rate
      in those patients inseminated with sperm incubated in culture medium vs CG (27%
      vs 47%, P < .05 t-test). Similarly, a higher percentage of patients receiving
      culture medium treatment of sperm had failed fertilization (45%) compared to CG
      (11%). Though the clinical PRs were higher with CG (21%) tham medium (9.5%),
      there was no statistical difference. CONCLUSIONS: Though the percentage of sperm
      bound with antibodies are not reduced, we hypothesize that the CG treatment
      improves fertility by possibly mitigating the antagonistic action of these
      antibodies.

PMID- 7646767
TI  - Predictive factors in recurrent spontaneous aborters--a multicenter study.
AB  - PROBLEM: Compare data from several centers relating to success rates in recurrent
      spontaneous miscarriage and assess the significance of indicators of subsequent
      pregnancy loss. METHOD: Data from 777 couples with unexplained recurrent
      spontaneous abortion from independent studies at seven centers were analyzed
      using logistic regression analysis. The following covariates were considered: age
      of patient, number of previous spontaneous abortions, length of previous
      abortions history, sub-fertility index (defined as the product of the number of
      spontaneous abortions and the abortion history), whether a patient was a primary
      or secondary aborter, and whether a patient had received leukocyte immunotherapy.
      RESULTS: There was a highly significant difference between the seven centers in
      success rates in the subsequent pregnancy and a highly significant association
      between success rate and each of the following covariates: the number of previous
      abortions, the length of the previous abortion history and the sub-fertility
      index. In particular, for each increase of 10 units in the value of the sub
      fertility index, up to a value of 30, the odds in favor of a successful pregnancy
      decreased by a factor of 0.6, i.e., 40%. There was, however, little evidence of
      an association between the success rate in the subsequent pregnancy and age,
      parity, or immunization with cells from the husband. CONCLUSIONS: The sub
      fertility index may be a useful measure of likelihood of success in a subsequent
      pregnancy.

PMID- 7646768
TI  - Validation of an embryotoxicity assay.
AB  - PROBLEM: Culture of mouse blastocysts has served as a tool for identifying
      various embryotoxic factors in human serum. While inactivated, sera from
      recurrently aborting women inhibit mouse blastocyst development in vitro.
      Variation in results from individual serum samples has limited the usefulness of
      this assay in establishing a new classification of idiopathic recurrent
      spontaneous abortion (RSA). METHOD: Two-cell embryos were collected from
      superovulated mated CB6F1/J mice and cultured in Ham's F-10 media supplemented
      with 10% fetal bovine serum (FBS) or tested human serum at 37 degrees C with 5%
      CO2 and high humidity. Each sample was assayed in triplicate using three mice
      with at least five embryos from the same mouse per dish. Development was
      evaluated at 72 h and the frequency of atretic embryos was recorded. RESULTS:
      Intrasample (interassay) variation yielded a coefficient of variation of 9%. When
      repeated, samples from a given individual were evaluated and the coefficient of
      variation was 8.7%. Interoperator variability was 4% interassay and 2% intrassay.
      Atresia of embryos was 23% when incubated with FBS (N = 122), 21% in FC (N =
      122), and in the sera of patients with RSA 34.6% (N = 95). Results of percentage
      of atresia from the fertile control group had a nonparametric distribution. Using
      2.2 multiples of the median to determine the 95% confidence interval, a threshold
      at 44.0% of atresia was established. CONCLUSIONS: The critical step in
      maintaining low variability in this bioassay is to control mouse variability by
      averaging the percentage atresia from different mice as embryo donors for each
      tested serum. A subgroup of 24% (23/95) RSA patients who displayed embryotoxic
      activity was identified with a specificity of 95% and positive predictive value
      of 83%, P = 0.001.

PMID- 7646769
TI  - Fertility among women with recurrent spontaneous abortions--the effect of
      paternal cell immunization treatment.
AB  - PROBLEM: The risk of women whose chief complaint is recurrent spontaneous
      abortions (RSA) for secondary infertility (infecundability) has not been
      evaluated prospectively. The effect of paternal mononuclear cell immunization on
      conception rates is unknown. METHOD: Two hundred women whose chief complaint was
      RSA were randomly assigned to be immunized with paternal mononuclear cells either
      before or after (up to 6 postmenstrual weeks) conception. Fertility rates (both
      conception and live birth) were evaluated for the group immunized before
      conception and compared to those for the control group, who were not immunized
      until after conception, using life table and multiple logistic regression
      analyses. RESULTS: Prospectively ascertained, age-related conception rates for
      nonimmunized RSA controls appeared to be similar to those for general
      populations. Immunization before pregnancy had no significant effect (power +/-
      14%) on rates of conception (66% before, 77% after) or time to conceive (median
      weeks before 19.5, after 27.0). Live birth rates (before 59%, after 63%) were
      also similar for both groups (P = 0.7). CONCLUSION: Women whose only prior
      complaint was RSA were not at high risk for secondary infecundability, and
      immunization did not alter either conception rates or time to conceive.
      Postponement of immunization until after conception did not affect live birth
      rates for women selected for study because they did not have a history of prior
      infecundability or early repeated miscarriages.

PMID- 7646770
TI  - Inhibition of induced lymphocyte proliferation by lipid and protein components of
      the syncytiotrophoblast plasma membrane.
AB  - PROBLEM: The aim of this work was to define the respective responsibilities of
      the lipid and protein components of syncytiotrophoblast plasma membranes on the
      inhibition of lymphocyte proliferation induced in vitro. METHOD: A fractionation
      method using octyl-beta-D-glucopyranoside enabled lipoprotein, lipid, and protein
      fractions to be isolated from the membrane. RESULTS: The lipid fraction was shown
      nonspecifically to inhibit lymphocyte proliferation, to a lower extent compared
      with the native membrane. Alternatively, the protein fraction used as a
      proteoliposome contained the totality of the cytostatic effect of the native
      fraction. CONCLUSION: These results are discussed generally in the context of the
      immunoregulatory role of membrane lipids and proteins and in relation to the
      local properties of syncytiotrophoblast plasma membrane components in fetal graft
      tolerance.

PMID- 7646771
TI  - Alloimmunization against well defined polymorphic major histocompatibility or
      class I MHC transfected L cells antigens can prevent poly IC induced fetal death
      in mice.
AB  - METHOD: It is possible to induce increased fetal resorption in a number of inbred
      murine matings by injecting Poly (I) Poly (C12U) 3.5 days postconception, a
      maneuver associated with natural killer-mediated damage to the feto placental
      unit such as occurs in spontaneous fetal resorptions. RESULTS: We show here that
      alloimmunization can block this effect. In addition, maternal immune responses
      induced by alloimmunization against isolated mutant class I or class II, as well
      as by immunization with class I MHC alloantigens (Kd) transfected L cells are
      sufficient to restore normal fetal viability. It is not necessary that the
      maternal immune response be specifically directed against paternal alloantigens
      fr the fetal protection to ensue, since the effect occurs in inbred matings when
      the mother is immunized against unrelated class I or class II alloantigens. As in
      previous studies conducted in the murine species, not all MHC alloimmunizations
      are protective. In addition, as control, immunization with a monomorphic class I
      MHC molecular (37), transfected L cells, sheep red blood cells or hen egg
      lysozyme is without effect. CONCLUSION: These results indicate that defined MHC
      antigens can mediate fetal protection from induced fetal resorption, and suggest
      that one driving force in promoting MHC antigen polymorphism in mammals is their
      capacity to confer protection from NK mediated fetal demise.

PMID- 7646772
TI  - [Theory of similarity between close relative species of toxic medicinal herbs in
      toxicity and poisoning action].
AB  - The article puts forward an opinion that there are identical or similar toxic
      components and poisoning action among close relative species of toxic medicinal
      herbs. These components, however, may vary in contents with different species.
      Many scientific examples are enough to prove that we can take treating, curing
      and preventative measures effectively only if we hold the conception that
      "Toxicity and poisoning action to each other may exist in close relative species
      of toxic medicinal herbs".

PMID- 7646773
TI  - [Comparative studies on the ethnomedicines from West Sichuan Highlands in China].

PMID- 7646774
TI  - [Study on economic NPK(nitrogen-phosphorus-potassium)-requirements for medicinal
      safflower].
AB  - A design of second order orthogonal rotative regression was developed and field
      tested, and a model for obtaining 18kg/mu dry flower yield was simulated and
      built according to several better combinations based on the model of total
      safflower dry flower yield. The optimal NPK-requirements for obtaining the above
      18kg/mu dry flower yield are N:6-6.5kg/mu, P2O5:10.0-11.0kg/mu, K2O:6.9
      10.0kg/mu. These requirements may be adjusted rationally according to soil
      fertility, manure sources, and so on.

PMID- 7646775
TI  - [Influence of heating degrees on appearance of calcined shell drugs].
AB  - The colors, crisp extents and comminution rates of 4 kinds of shell drugs
      calcined under various conditions were conpared systematically. The appearance
      alterations of the calcined drugs were closely related to the heating degrees
      during calcining operation, and the effect of calcining duration was greater than
      that of calcining temperature.

PMID- 7646776
TI  - [Quantitative determination of genkwanin in flos Genkwa by TLC-densitometry].
AB  - The contents of genkwanin in Flos Genkwa processed in different ways were
      determined by TLC-densitometry. The result showed that the contents of genkwanin
      in different samples were 0.128%-0.389% and the rate of recovery was 98.8%, thus
      offering a reference to the selection of top processing technology.

PMID- 7646777
TI  - [Bioavailability study on xiaohuoluo pills].
AB  - According to the relationship between dosage and effect, the time course of
      analgesic was determined after oral administration of Xiaohuoluo Pills to mice.
      Based on this experiment, contrasting the commercial pills with the reference
      preparation, the bioavailability of Xiaohuoluo Pills was studied. It was shown
      that the bioavailability of different batches of product from the same factory
      was different. This method was good for the study of compound preparations of
      Chinese materia medica.

PMID- 7646778
TI  - [Determination of piperylpiperidine in wuwei qingzhuo powder by reversed phase
      HPLC].
AB  - A quantitative method has been developed for the determination of
      piperylpiperidine in Wuwei Qingzhuo powder by reversed phase HPLC. The average
      recovery is 102.0% (RSD = 0.46%) and lowest detection concentration 0.03
      microgram/ml. The linear range of piperylpiperidine is 1.875-30 micrograms/ml, r
      = 0.9999.

PMID- 7646779
TI  - [Determination of ursodeoxycholic acid and chenodeoxycholic acid in Chinese
      medicinal compound preparations by TLC-densitometry].
AB  - The contents of ursodeoxycholic acid (UDCA) and chenodeoxycholic acid (CDCA) in
      Chinese medicinal compound preparations have been determined by TLC-densitometry.
      The determination wavelength was 375nm and reference wavelength was 700nm. For
      UDCA the linear range was 3.0-15.0 micrograms and recovery was 97.2% (RSD =
      1.2%), and for CDCA the linear range was 4.0-20.0 micrograms and recovery was
      99.3% (RSD = 2.1%).

PMID- 7646780
TI  - [Alkaloid constituents in the seeds of Sophora viciifolia Hance].
AB  - Six alkaloids were isolated from the mature seeds of Sophora viciifolia for the
      first time. On the basis of physicochemical and spectroscopic analysis, their
      structures have been identified as oxymatrine, oxysophocarpine, matrine,
      sophocarpine, sophoramine and sophoridine.

PMID- 7646781
TI  - [Chemical constituents of Euphorbia nematocypha Hand.-Mazz].
AB  - Four compounds were isolated from the roots of Euphorbia nematocypha. Three of
      them were identified as A'-neogammacer-22(29)-en-3 beta-ol (18 beta.21 alpha)
      (II), jolkinolide E (III) and beta-sitoesterol (IV). Among them, II was obtained
      from the genus Euphorbia and III from this plant for the first time.

PMID- 7646782
TI  - [Stimulating action of Carthamus tinctorius L., Angelica sinensis (Oliv.) Diels
      and Leonurus sibiricus L. on the uterus].
AB  - The experimental results indicate that the decoction of Chinese drugs Carthamus
      tinctorius, Angelica sinensis and Leonurus sibiricus has stimulating action on
      the uterus of mouse in vitro. The stimulating action of Carthamus tinctorius and
      Leomurus sibiricus has been found related to stimulating H1-receptor and alpha
      adrenergic receptor of uterus, but the action of Angelica sinensis to stimulating
      H1-receptor of uterus only.

PMID- 7646783
TI  - [Antitussive, expectorant and anti-asthmatic effects of Cynanchum glaucescens
      (Decne.) Hand. -Mazz].
AB  - The water, ethanol and ether extracts from Cynanchum glaucescems administrated
      orally showed significant antitussive effect in ammonia-induced cough model in
      mice. The water and ethanol extracts had obvious expectorant effect. The filtered
      solution of water decoction injected intraperitoneally could effectively prevent
      guinea pigs from asthma induced by acetulcholine and histamine mixture, and also
      inhibit the ear inflammation in mice caused by croton oil. All these effects
      showed close dose-effect relationship.

PMID- 7646784
TI  - [Promoting effects of rhizoma Drynariae on the calcification of cultivated chick
      embryo bone primordium].
AB  - It has been discovered by tissue cultivation and isotope tracing that the
      injection of Rhizoma Drynariae significantly promotes the calcification of chick
      embryo bone primordium in vitro, increases the ALP activity of cultivated tissues
      and accelerates the synthesis of proteoglycan. It has also been proved that the
      promotion of the synthesis of proteoglycan is an important factor of the
      promotion of calcification.

PMID- 7646786
TI  - [An investigation of medicinal Trichosanthes].
AB  - This paper reports the distribution, habitats and medical usages of 14 species of
      medicinal Trichosanthes produced in China. Among them, there is a new species
      named Trichosanthes mianyangensis. A key for the identification of all these 14
      species has been compiled and presented.

PMID- 7646785
TI  - [Effect of Dendrobium nobile Lindl. on gastric acid secretion, serum gastrin and
      plasma somatostatin concentration].
AB  - The patients with chronic superficial gastritis were perfused in the stomach with
      20 g of Dendrobium nobile to observe the variations in gastric acidity output,
      serum gastrin and plasma somatostatin concentration. The result showed a
      significant increase in both acidity output and serum gastrin concentration (P <
      0.01). No significant change occurred in plasma somatostatin concentration (P >
      0.05).

PMID- 7646787
TI  - [Saponins of radix Ginseng and radix quiquefolius].

PMID- 7646788
TI  - [Establishment and application of paper strip analysis for products processed
      with honey].
AB  - This method was applied for the qualitative and quantitative analysis of 12 kinds
      of products processed with honey. The method is simple, convenient, objective in
      qualification and accurate in qualification, thus suitable for quality control of
      product processed with honey.

PMID- 7646789
TI  - [Optimization of preparation technology for migao xinle dripping pilules by
      uniform design method].
AB  - According to the factors that affect the quality of Migao Xinle dripping pilules,
      an optimization of preparation technology is studied by uniform design method.
      Several quality indexes are tested and the result of experiment is satisfactory.

PMID- 7646790
TI  - [Experimental studies on the quality of sophora powder].
AB  - In this paper, the contents of total flavonoids, essential oil, tannin, trace
      elements along with bacteriostatic action in Sophora Powder have been measured.
      These studies present a scientific evaluation on the quality of Sophora Powder.

PMID- 7646791
TI  - [Identification of chaihu guizhi ganjiang decoction by three dimensional HPLC].
AB  - The Chaihu Guizhi Ganjiang Decoction was identified by three dimensional HPLC.
      The result showed that the constituents in this decoction, namely Radix Bupleuri;
      Ramulus Cinnamomi; Radix Glycyrrhizae and Radix Scutellariae could all be
      identified clearly.

PMID- 7646792
TI  - [Constituents of lignanoids in Siphonostegia chinensis Benth].
AB  - A trace monomeric compound was isolated from the aerial part of Siphonostegia
      chinensis, and determined by X-ray diffraction as a lignanoid compound named
      syringaresinol. It is obtained from this plant as well as from Scrophulariaceae
      for the first time.

PMID- 7646793
TI  - [Separation and identification of the anti-inflammatory diterpene from the root
      cortices of Acanthopanax gracilistylus W. W. Smith].

PMID- 7646794
TI  - [Chemical constituents of Impatiens siculi fer Hook.f].

PMID- 7646795
TI  - [Anti-lipid peroxidation effects of sini decoction and its components on ischemic
      myocardium and the dose- and time-effects].
AB  - The complete Sini Decoction can significantly reduce the content of MDA in
      ischemic myocardium. Single ingredients of the decoction, such as Radix Aconoti
      Praeparata or Radix Glycyrrhizae, except Rhizoma Zingiberis, also have similar
      effect but inferior to that of the complete decoction. Under the present
      conditions of experiment, anti-lipid peroxidation of Sini Decoction is
      significant at doses ranging from 0.05 to 0.2ml/20g administered for 2-7 days at
      0.1ml/(20g.d).

PMID- 7646796
TI  - [Effects of Sichuan herba Epimedii on the concentration of plasma middle
      molecular substances and sulfhydryl group of "yang-deficiency" model animal].
AB  - The effects of tonifying the kidney and strengthening the "Yang" produced by the
      extracts of Chinese herbs Epimedium wushanense and E. pubescens were studied in
      this paper. The results showed that both two herbs could decrease the
      concentration of plasma middle molecular substances and increase the
      concentration of plasma sulfhydryl group of "Yang-deficiency" model mice, thus
      suggesting that the above-said tonifying and strengthening effects of Herba
      Epimedii may result from its effects on middle molecular substances and
      sulfhydryl group, so as to strengthen the body resistance and eliminate the
      invading pathogenic factors.

PMID- 7646798
TI  - [An experimental study on the integrated effects of heat-cleaning and detoxifying
      drugs and fire-purging drugs used in combination].
AB  - Heat-cleaning and detoxifying drugs and fire-purging drugs used in combination
      have been proved able to restore the endotoxin-induced deviant of HCT, blood
      viscositites, PTT and fibrinolytic activity, and reduce the blood content of both
      endotoxin and PGE2 in rabbits. In addition, the combination can also decrease the
      pes swelling percentage in rats as well as evans blue extravasation volume in
      mice. In practice, however, it should be noted that the bitter and cold qualities
      of these two kinds of drugs may be harmful to health.

PMID- 7646797
TI  - [Protective effect of total flavonoids of radix Astragali on mammalian cell
      damage caused by hydroxyl radical].
AB  - The protective effect of total flavonoids of Radix Astragali (TFA) on V79 cell
      damage caused by H2O2-Fe2+ system has been studied. The results show that total
      flavonoids of Radix Astragali inhibit lipid peroxides and increase SOD activity.
      It has also been found that TFA has different protective effect against various
      damages of V79 cells caused by hydroxyl radical.

PMID- 7646799
TI  - [General introduction to traditional methods of calcining Chinese shell drugs].

PMID- 7646800
TI  - [A review on the research of genuine traditional Chinese drugs].

PMID- 7646801
TI  - [Experimental study and textual research on whether the genus of Pyrola contains
      arbutin].
AB  - Thin layer chromatography and high performance liquid chromatography show that
      Pyrola calliantha does not contain arbutin. Literature survey shows that to date
      no one has ever isolated arbutin from this herb.

PMID- 7646803
TI  - [Influence of heating degrees on internal quality of calcined shell drugs].
AB  - The internal quality of 4 kinds of shell drugs calcined under different
      conditions was investigated and compared in terms of the yielding ratios and
      total calcium content of the calcined product, Ca2+ content of the decoction and
      total water-soluble extractive rate. It was found that at calcining temperatures
      higher than 800 degrees C the internal quality of the shell drugs would change
      markedly.

PMID- 7646802
TI  - [Influence of processing on contents of genkwanin in flos Genkwa].

PMID- 7646804
TI  - [Examination on extraction technology for radix Sophorae Flavescentis by means of
      orthogonal experiment design].
AB  - The extraction and purificatory crafts for Radix Sophorae Flavescentis were
      observed through the orthogonal experiment design using matrine as the fixed
      indicatrix for TLC-scanning. Quantitative analyses of matrine were made on the
      momentum parameters of the different craft conditions. The results of the three
      different extraction methods show that the best way is to use 2% gelatin to
      remove tannin with the least loss of matrine, and that the ethanol extract from
      water precitation is better than the water extract from ethanol precipitation.

PMID- 7646805
TI  - [Two-dimensional thin layer chromatographic-colorimetric determination of
      Astragalus saponin 1 in suanqi oral liquid].
AB  - Extracted by n-butanol and separated by two-dimensional TLC, the astragalus
      saponin 1 in Suanqi Oral Liquid was determined by vanillin-perchloric acid
      colorimetric method. The recovery and RSD were 96.3% (n = 5) and 0.75%
      respectively.

PMID- 7646806
TI  - [Determination of andrographolide in medicinal preparations by HPLC].
AB  - A HPLC procedure has been developed to determine andrographolide in Fencishui.
      The sample was analyzed on a YWG-C18 column, with methanol-water (38:62) as the
      mobile phase, and detected at 225nm. The average recovery was 98.42% and RSD
      1.69%.

PMID- 7646807
TI  - [Chemical constituents of Sparganium stoloniferum Buch.-Ham].

PMID- 7646808
TI  - [Determination of hyperin in Epimedium koreanum Nakai by HPLC].
AB  - A HPLC method for the determination of hyperin in Epimedium koreanum was
      investigated. The result shows that this method is simple, specific and accurate.
      The recovery was 97.4% and relative standard deviation was 1.2%. With good
      reproducibility and wide response linearity, the method can be used for the
      quality control of this herbal medicine.

PMID- 7646809
TI  - [Effects of 3 kinds of decoction on serum gastrin, gastrin cell density and the
      content of PGE2 of gastric antral mucosa in experimental chronic gastritis in
      rats].
AB  - Experimental chronic gastritis (ECG) models were established in rats by inserting
      a spring into pyloric canal as well as feeding sodium deoxycholate. An experiment
      was undertaken to observe the therapeutic effects of three formulas of
      traditional Chinese medicine "Shipitong" (SPT), "Ganpingyangwei" (GPYW) and
      "Weile" (WL). The experimental results show that all of the three decoctions can
      make serum gastrin, gastrin cell density and amount of antral mucosal PGE2 of the
      ECG rats return to normal levels.

PMID- 7646810
TI  - [Antitumor effect in vitro and immuno-response in vivo of fructus Mume].
AB  - The antitumor action of extracts from Fructus Mume and the main triterpenoid
      component ursolic acid on HIMeg and HL-60 cells in vitro was tested. The immuno
      response in rats was also studied. The result showed that Fructus Mume had
      inhibiting effect on proliferation of HIMeg and HL-60 cells.

PMID- 7646811
TI  - [Protective effect of semen Ziziphi spinosae on superoxide dismutase reduction in
      mice with endotoxin fever].
AB  - An animal model with decreasing SOD was established by fever from intravenous
      injection of endotoxin. The SOD level was measured by RIA in the animal serum and
      liver tissues. The results indicated that the SOD level of the model group was
      obviously lower than that of the normal group (P < 0.05), but the level of the
      group treated with Semen Ziziphi Spinosae was higher than that of the model
      group. The study shows that Semen Ziziphi Spinosae can protect mice with
      endotoxin fever from SOD decrease.

PMID- 7646812
TI  - A receptor that subserves reovirus binding can inhibit lymphocyte proliferation
      triggered by mitogenic signals.
AB  - A novel surface receptor complex involved in inhibition of T-cell proliferation
      is described. Biochemical isolation revealed two non-covalently associated
      proteins of about M(r) 65,000 (p65) and 95,000 (p95). These polypeptides may be
      related. The p65 form is expressed after cellular activation and replication and
      is recognized by monoclonal antibody (mAb) 87.92.6 or reovirus hemagglutinin as
      unnatural ligands. The p95 species is associated with tyrosine kinase enzymatic
      activity. Receptor ligation results in rapid alteration of the phosphotyrosine
      content of cellular substrates, and this activity correlates with
      antiproliferative effects. The inhibition of proliferation is a time-dependent
      reversible arrest at the G1-S phase of the cell cycle. Activation through the T
      cell receptor, protein kinase C, or addition of cytokines does not reverse the
      antiproliferative effect. This receptor complex may define novel features of T
      cell proliferation.

PMID- 7646813
TI  - Specificity of action of a herpes virus VP16/tetracycline-dependent trans
      activator in mammalian cell cultures.
AB  - In this work, we have studied the activity of a tetracycline modulatable trans
      activator (tTA) generated by fusing the DNA binding domain of the tetracycline
      repressor to the trans-activation domain of the Herpes simplex virus protein 16
      (HSV VP16) (plasmid pUHD15-1Neo). In the three different cell lines studied (HTC,
      rat hepatoma; T47D, human breast cancer; SK-N-BE, human neuroblastoma), the
      expression of the luciferase gene under the control of a tetracycline operator
      sequence (plasmid pUHC13-3) was used as a control of the incorporation and the
      functionality of the trans-activator. Clones selected from these cells responded
      in a time and dose-dependent manner to the withdrawal of tetracycline. In all
      these clones, the tTA trans-activator not only modulates the activity of the
      luciferase gene, but also modulates the activity of a number of endogenous
      proteins, including C/EBP beta, the glucocorticoid receptor (GR), and SP1. In the
      transfected cells, the level of these transcription factors was strongly
      inhibited in the presence of tetracycline and was highly increased after
      tetracycline removal. Electrophoresis mobility shift assay (EMSA) and footprint
      experiments proved that the induced proteins are perfectly efficient in binding
      the DNA. Their transcriptional activity was also determined. In HTC/A9 cells, the
      level of the chloramphenicol acetyltransferase (CAT) expression driven by the
      promoter of the alpha 1-glycoprotein (AGP) gene was strongly enhanced at 72-84 hr
      following removal of tetracycline from the growth media. The accumulation of the
      endogenous AGP mRNA also increased at 84 hr. In the T47D/TA11 and SK-N-BE/C2.6
      cells, a general activation of protein synthesis was also evidenced.

PMID- 7646814
TI  - Cloning, chromosomal localization, and RNA expression of a human beta chemokine
      receptor-like gene.
AB  - A human cDNA encoding a putative G protein-coupled receptor designated chemokine
      beta receptor-like 1 (CMKBRL1) was isolated from an eosinophilic leukemia
      library. Its deduced sequence is approximately 40% identical to previously cloned
      receptors for the beta chemokines macrophage inflammatory protein-1 alpha (MIP-1
      alpha), RANTES, and monocyte chemoattractant protein-1 (MCP-1), which are
      chemoattractants for blood leukocytes, and is 83% identical to the product of the
      orphan rat cDNA RBS 11. Like the MIP-1 alpha/RANTES receptor, CMK-BRL1 is encoded
      by a small, single-copy gene that maps to chromosome 3p21 and is expressed in
      leukocytes. However, two screening assays with a broad panel of chemokines failed
      to identify its ligand. CMKBRL1 mRNA was detectable by Northern blot
      hybridization in neutrophils and monocytes, but not eosinophils, and was also
      found in eight solid organs that were tested with particularly high expression in
      brain. The RNA distribution of the known beta chemokine receptors was overlapping
      but distinct from that of CMKBRL1. MIP-1 alpha/RANTES receptor mRNA was
      detectable in neutrophils, monocytes, eosinophils, and in all eight solid organs
      tested, with particularly high expression in placenta, lung, and liver. MCP-1
      receptor mRNA was found in monocytes, lung, liver, and pancreas. These results
      suggest that the ligand for the putative CMKBRL1 receptor is a beta chemokine
      that targets both neutrophils and monocytes. Moreover, the RNA distributions
      suggest that CMKBRL1, the MIP-1 alpha/RANTES receptor, and the MCP-1 receptor may
      have both overlapping and distinct biological roles.

PMID- 7646815
TI  - Role of the transcription factor C/EBP beta in expression of a rat pregnancy
      specific glycoprotein gene.
AB  - Pregnancy-specific glycoproteins (PSGs), which are the major placental proteins,
      and the carcinoembryonic antigens comprise a subfamily within the immunoglobulin
      superfamily. To understand the molecular mechanisms underlying the control of PSG
      expression, we characterized the promoter elements of a rodent PSG gene, rnCGM3,
      and showed that DNA elements at nucleotides -326 to -185 (PI) relative to the
      translation start site of rnCGM3 function as a promoter. The rnCGM3 PI promoter
      contains two placental factor binding sites, PISI and PISII. Both are
      transcription activation elements. In the present report, we screened a placental
      expression cDNA library with a rnCGM3-PISII probe (nucleotides -263 to -233)
      encompassing two overlapping palindromes (TGTTGCTCAACATGTTG) and demonstrated
      that the PISII-binding factor is C/EBP beta, a leucine zipper family of
      transcription factor. Gel mobility-shift and transient expression analyses showed
      that C/EBP beta and C/EBP isoforms, C/EBP alpha and C/EBP delta, bind to the
      PISII element and trans-activate rnCGM3 gene expression. Deletion of PISII from
      the rnCGM3 PI promoter greatly reduced the basal as well as the C/EBP-activated
      rnCGM3 expression. Gel supershift assays demonstrated that C/EBP beta is the
      placental isoform that binds to the PISII site rnCGM3. Moreover, C/EBP beta is
      expressed in high levels in the placenta, ovary, liver, lung, heart, and spleen,
      in contrast to C/EBP alpha, which is expressed primarily in the liver and only
      low levels in the placenta. Our results demonstrate that C/EBP beta is one of the
      transcription factors that positively regulate rnCGM3 expression during
      pregnancy.

PMID- 7646816
TI  - Impact of altered actin gene expression on vinculin, talin, cell spreading, and
      motility.
AB  - Previous studies have demonstrated a strong correlation between the expression of
      vinculin and the shape and motility of a cell (Rodriguez Fernandez et al., 1992a,
      b, 1993). This hypothesis was tested by comparing the expression of vinculin and
      talin with the motility of morphologically altered myoblasts. These mouse C2
      myoblasts were previously generated by directly perturbing the cell cytoskeleton
      via the stable transfection of a mutant-form of the beta-actin gene (beta sm) and
      three different forms of the gamma-actin gene; gamma, gamma minus 3'UTR (gamma
      delta'UTR), and gamma minus intron III (gamma delta IVSIII) (Schevzov et al.,
      1992; Lloyd and Gunning, 1993). In the case of the beta sm and gamma-actin
      transfectants, a two-fold decrease in the cell surface area was coupled, as
      predicted, with a decrease in vinculin and talin expression. In contrast, the
      gamma delta IVSIII transfectants with a seven-fold decrease in the cell surface
      area showed an unpredicted slight increase in vinculin and talin expression and
      the gamma delta 3'-UTR transfectants with a slight increase in the cell surface
      area showed no changes in talin expression and a decrease in vinculin expression.
      We conclude that changes in actin gene expression alone can impact on the
      expression of vinculin and talin. Furthermore, we observed that these actin
      transfectants failed to show a consistent relationship between cell shape,
      motility, and the expression of vinculin. However, a relationship between talin
      and cell motility was found to exist, suggesting a role for talin in the
      establishment of focal contacts necessary for motility.

PMID- 7646817
TI  - Expression of the c-ski proto-oncogene during cell cycle arrest and myogenic
      differentiation.
AB  - Although the ski oncogene plays a role in cell proliferation, morphological
      transformation, and myogenic differentiation, the myogenic activities of the
      proto-oncogene c-ski have yet to be elucidated. c-ski is expressed within
      myoblasts during embryogenesis. Transcripts from the proto-oncogene can be
      detected in somites early in myogenic commitment, as well as in terminally
      differentiated skeletal muscle. However, c-ski mRNAs expressed in cells of the
      myogenic lineage are indistinguishable from c-ski transcripts in other cell
      types, raising the possibility that muscle-specific c-ski transcripts are
      expressed transiently. Avian cell lines QM7 and QM5 were used as a model to
      analyze changes in expression and alternative exon usage of c-ski during
      synchronous muscle differentiation. Upon serum deprivation, QM7 cells undergo
      myogenic differentiation. In contrast, QM5 cells cease proliferation but do not
      differentiate. Results show that levels of expression and alternative splicing of
      c-ski transcripts remain unchanged during cell cycle arrest or myogenic
      differentiation.

PMID- 7646818
TI  - Reporter gene expression upon stable transfection when only a TATA box or a TATA
      box plus Sp1 sites are present 5' to the gene.
AB  - Episomal plasmids for stable transfection of mammalian cell cultures were
      constructed that have a G418-resistance (neo) gene immediately downstream of a
      highly truncated promoter. These plasmids had a function hygromycin-resistance
      gene (hyg) as a selectable marker. Surprisingly, in LTK- cells, but not HeLa
      cells, stably transfected with these BK virus-based plasmids having no promoter
      elements adjacent to the neo gene, readthrough transcription, probably from about
      1 kb upstream, gave almost as efficient expression of the neo gene as of the hyg
      gene with a full-length promoter immediately upstream. When the transfecting
      plasmids contained Epstein-Barr virus (EBV) DNA sequences for episomal
      maintenance and had multiple Sp1 sites and a TATA box as the only promoter
      elements 5' to the neo gene, only about 3-9% of HeLa transfectants were G418
      resistant (G418R). In transfections with analogous plasmids lacking these
      promoter elements 5' to the neo gene, no G418R colonies were seen. The
      establishment of the G418R phenotype probably required integration of plasmid DNA
      into favorable chromosomal sites and was aided by the presence of the TATA box
      plus Sp1 sites as a subminimal promoter. The absence of detectable G418
      resistance in most of the HeLa transfectant clones obtained with EBV-type
      plasmids, even at a high plasmid copy number and even when a TATA box and six Sp1
      sites were present immediately upstream of the neo gene, indicates that these
      elements do not suffice for appreciable gene expression in vivo and that this is
      a suitable model system for studying DNA rearrangements that can potentiate
      expression of the neo gene.

PMID- 7646819
TI  - Cloning and characterization of the NADPH cytochrome P450 oxidoreductase gene
      from the filamentous fungus Aspergillus niger.
AB  - In this paper, we describe the cloning and molecular characterization of the
      Aspergillus niger cytochrome P450 reductase (CPR) gene, cprA. Attempts to clone
      the cprA gene by heterologous hybridization techniques were unsuccessful. Using
      the polymerase chain reaction (PCR) with degenerate primers based on conserved
      regions found in cpr genes from other organisms, we were able to isolate a
      fragment that contained part of the gene. With the aid of this fragment, a
      genomic fragment containing the entire coding region and 5' and 3' untranslated
      ends of the cprA gene was isolated and sequenced. The cprA gene was introduced in
      multiple copies in A. niger strain N402 using the amdS transformation system. One
      of the resulting transformants, AB2-2, showed a 14-fold increase in CPR activity,
      indicating that the cloned cprA gene is functional. We analyzed the induction of
      cprA gene expression by several generally used cytochrome P450 inducers but did
      not find any induction of cprA gene expression. However, A. niger cprA gene
      expression could be induced by benzoic acid, which is the substrate of the highly
      inducible A. niger cytochrome P450 gene, bphA (cyp53). On the basis of a
      comparison of the deduced protein sequence of the A. niger cprA gene with CPR
      proteins isolated from other organisms, the structure-function relationship of
      some conserved regions is discussed.

PMID- 7646820
TI  - What is the true clinical significance of plasma protein binding displacement
      interactions?

PMID- 7646821
TI  - Hirudin and excess bleeding. Implications for future use.

PMID- 7646822
TI  - Which drugs affect potassium?
AB  - A number of drugs can affect potassium levels by a variety of different
      mechanisms. Diuretics remain the most important cause of drug-induced
      alterations. ACE inhibitors may produce hyperkalaemia, particularly in patients
      with autonomic neuropathy, adrenal insufficiency, renal impairment and when used
      in combination with nonsteroidal anti-inflammatory drugs (NSAIDs). Cathartic
      and/or diuretic abuse should be suspected when hypokalaemia occurs in young
      patients suspected of having an eating disorder. NSAIDs may occasionally produce
      hyperkalaemia, particularly in patients with renal impairment or when used with
      ACE inhibitors. Sympathomimetics and theophylline derivatives may lower serum
      potassium levels, but this is usually only of clinical significance when
      overdosage occurs.

PMID- 7646823
TI  - Prevention and management of extravasation of cytotoxic drugs.
AB  - Extravasation of certain cytotoxic agents during peripheral intravenous
      administration may cause severe local injuries. Most extravasation can be
      prevented with the systematic implementation of careful administration
      techniques. However, the management of this complication, the aim of which is to
      prevent progression to tissue necrosis and ulceration, remains an important
      challenge in the care of cancer patients. Many antidotes have been evaluated
      experimentally and a few may be able to reduce the local toxicity of the more
      common vesicant cytotoxic drugs. Because no randomised trial on the management of
      cytotoxic drug extravasation in humans has ever been completed, recommendations
      must be based on the more consistent experimental evidence and on cumulative
      clinical experience from available case reports and uncontrolled studies, which
      are reviewed in this article. Empirical guidelines recommend the use of topical
      dimethylsulfoxide (DMSO) and cooling after extravasation of anthracyclines or
      mitomycin, locally injected hyaluronidase after extravasation of vinca alkaloids,
      and locally injected sodium thiosulfate (sodium hyposulfite) after extravasation
      of chlormethine (mechlorethamine; mustine). Plastic surgery may be necessary when
      conservative treatment fails to prevent ulceration. The possibility of late local
      reactions must also be considered in the management of patients receiving
      chemotherapy.

PMID- 7646824
TI  - Ocular adverse effects of neuropsychiatric agents. Incidence and management.
AB  - Neuropsychiatric agents may adversely affect the eye in various ways. The more
      frequently encountered effects include corneal oedema and pigmentary changes in
      the lens and cornea which are induced by phenothiazine derivatives; thioridazine
      induced retinopathy; tricyclic antidepressant-induced accommodation interference
      and glaucoma; and lithium carbonate-induced exophthalmos and papilloedema.
      Several adverse effects, such as corneal oedema, retinopathy and glaucoma, are
      vision-threatening, and patients often fail to describe their symptoms properly.
      A more precise understanding of these conditions is essential for prompt
      diagnosis and appropriate treatment.

PMID- 7646825
TI  - New antimalarials. A risk-benefit analysis.
AB  - Although more than 40% of the world's population live in malaria endemic areas,
      there are only 6 available antimalarial drugs for the treatment of Plasmodium
      falciparum infections. Three of these have been developed in the last 20 years
      and are discussed in this review. Mefloquine is relatively well tolerated and has
      the advantage of a single day regimen. It has ideal properties for prophylactic
      use. However, although rare, serious adverse reactions do occur and the drug
      cannot be used in severe malaria. Resistance has already emerged in some parts of
      the world. Halofantrine is also well tolerated and has a rapid antimalarial
      activity. It is more expensive than other antimalarials and the existence of
      cross-resistance links its usefulness to the demise of mefloquine. The discovery
      of a potentially lethal cardiotoxicity associated with halofantrine casts a
      further shadow over its use. The artemisinin derivatives represent an exciting
      breakthrough in the treatment of malaria. They are cheap and have a very rapid
      action. They seem remarkably free from toxic adverse effects, although the
      neurotoxicity seen in animal studies with the liposoluble derivatives gives rise
      for concern. However, the lack of pharmacokinetic and toxicity data as yet
      preclude their approval by Western drug regulation authorities. All antimalarials
      are threatened by the emergence of parasite resistance. Combination therapy using
      mefloquine and an artemisinin derivative may provide a way in which resistance
      can be combated.

PMID- 7646826
TI  - A risk-benefit assessment of zidovudine in the prevention of perinatal HIV
      transmission.
AB  - Mother-to-child transmission is the main mode of acquisition of HIV infection for
      children, and the estimated rate of vertical transmission ranges from 15 to 20%
      in Europe, 15 to 25% in the US and 25 to 35% in Africa. Vertical transmission is
      associated with clinical and immunological progression of disease in the mother,
      breastfeeding and possibly with vaginal delivery. Recently, the findings of the
      American/French AIDS Clinical Trial Group (ACTG) trial 076 showed that in women
      with mildly symptomatic HIV disease and no prior treatment with antiretroviral
      drugs during the pregnancy, zidovudine (ZDV, 3'-azido-3'-deoxythymidine, AZT)
      reduced the risk of vertical transmission when administered during pregnancy and
      delivery and to the infant in the first 6 weeks of life. No significant adverse
      effects were observed in either the mothers or neonates. Although the results of
      the American/French trial on the use of zidovudine to prevent vertical
      transmission are encouraging, many questions remain unanswered. The optimal
      timing of administration of zidovudine is unknown, as is its effectiveness in
      women with clinical characteristics that differ from those of the women in the
      trial. Concern has been expressed about the possibility of long term effects of
      exposure of zidovudine during pregnancy, both for the mother and the infant (of
      whom 4 out of 5 are uninfected anyway) and the implications for antenatal
      screening. Further trials with different zidovudine regimens and other strategies
      to prevent vertical transmission are being planned in several countries.

PMID- 7646828
TI  - Treatment of children suffering from cancer in Israel.

PMID- 7646827
TI  - Drug-induced lupus.
AB  - Drug-induced lupus is a syndrome resembling mild systemic lupus erythematosus
      which can complicate treatment with certain apparently unrelated therapies. The
      most common individual agents are procainamide and hydralazine. Drugs less
      frequently associated with the disease are chlorpromazine, isoniazid, methyldopa,
      penicillamine, quinidine and sulfasalazine. Whole drug groups have also been
      implicated, such as the anticonvulsants, beta-blockers, sulfonamides and some of
      the newer 'biological' agents. The syndrome is characterised by arthralgia,
      myalgia, pleurisy, rashes and fever in association with antinuclear antibodies in
      the serum. More serious features of idiopathic lupus such as nephritis and
      cerebral disease are rare in drug-induced disease. The pathogenesis is unknown
      but in some cases is thought to be due to interactions between the drug and DNA
      or histones, rendering them immunogenic. For the biological agents, including
      interferons and antibodies to tumour necrosis factor-alpha, it has been suggested
      that it is due to disruption of the cytokine network. Although extremely rare,
      recognition of drug-induced lupus is important because it reverts within a few
      weeks of stopping the drug. It is possible that understanding its pathogenesis
      may shed light on its more serious relative, systemic lupus erythematosus.

PMID- 7646829
TI  - The experience of South American mothers who have a child being treated for
      malignancy in the United States.
AB  - This phenomenological study examined the experience of South American mothers who
      brought their children to the United States for cancer treatment. Five mothers
      were interviewed twice about their subjective experiences. Data were analyzed
      using Colaizzi's method of phenomenology. Thirty-two significant statements were
      grouped into eight themes. The South American mothers brought their children to
      the United States in hopes of finding effective treatment, illustrating the major
      theme of our findings that no effort or sacrifice was too great to save their
      children's lives. The diagnosis of cancer had an overwhelming impact on the child
      and the family. This was made worse by the uncertainty of treatment outcome.
      Although the decision to come disrupted family life and caused economic and
      cultural hardship, it was uniformly believed to have been the right decision. The
      greatest challenges experienced by the mothers were language difficulties and the
      constant preoccupation with the child's illness. Through faith and a variety of
      coping strategies, these South American mothers succeeded in adapting. They
      transcended life disruption and focused on the critical goal of restoring their
      child's health. Central to their experience is that everything humanly possible
      be done to preserve the life of their child.

PMID- 7646830
TI  - Conscious sedation: a quality management project.
AB  - Conscious sedation provides effective pain control and can relieve anxiety
      associated with procedures. The increased use of this modality has prompted the
      American Academy of Pediatrics to develop national guidelines that emphasize the
      need for patient monitoring to ensure patient safety. A policy was developed that
      incorporated continuous monitoring of patients and frequent documentation of
      physiological measures before, during, and after procedures. All procedures over
      a 2-month period in the outpatient (n = 19) and inpatient (n = 24) pediatric
      oncology units that required midazolam and fentanyl were retrospectively
      analyzed. A nonrandom sample of one third of the inpatient procedures (n = 8) was
      also observed to assess the dynamics of monitoring and recording. Procedures,
      including recovery time, lasted an average of 69 minutes, with longer recovery
      periods recorded for the outpatient unit. Nurses, particularly on the inpatient
      unit, were not always able to provide continuous monitoring through recovery
      because of the demands of other patient assignments. This study suggests that to
      realistically meet the needs of the patients and the institution's
      responsibility, the current guidelines may need to be reconsidered to allow more
      nursing discretion in patient monitoring and/or the nurse's patient care
      assignment must be more flexible to allow for changing demands.

PMID- 7646831
TI  - Parse's theory of human becoming: an alternative guide to nursing practice for
      pediatric oncology nurses.
AB  - The Parse theory of human becoming guides nurses in their practice to focus on
      quality of life as it is described and lived. Parse's theory is presented here as
      an alternative approach for nursing practice in pediatric oncology. In this
      article, the human becoming theory is discussed and the practice dimensions and
      processes are described and illuminated with an example from nursing practice.

PMID- 7646832
TI  - Developing, implementing, and evaluating a handbook for parents of pediatric
      hematology/oncology patients.
AB  - This article details the development of a parent handbook for pediatric
      hematology and oncology patients. The planning and content development are
      discussed. Adult learning principles were incorporated throughout the handbook.
      Use of the handbook in a pediatric cancer center is described. Both subjective
      and objective methods were used to evaluate the handbook. Results from the
      evaluation verify the value of the handbook to parents and give direction for
      future revisions of the handbook.

PMID- 7646833
TI  - Multisite qualitative nursing research in pediatric oncology.

PMID- 7646834
TI  - The vinca alkaloids.

PMID- 7646835
TI  - Phase I pediatric oncology trials.

PMID- 7646836
TI  - Sharing care, grief, and next time.

PMID- 7646837
TI  - New approaches to structure analysis.
AB  - There are relationships among the phases and magnitudes of the structure factors
      that have not been extensively studied regarding their potential for enhancing
      procedures for structure determination. These relationships arise from a special
      way of writing the determinantal inequalities that form the necessary and
      sufficient conditions for a Fourier series to be non-negative. This particular
      form also lends itself readily to the development of probability measures by the
      use of the central limit theorem. Higher-order determinants are of interest. The
      relationships among the phases and magnitudes of the structure factors are
      algebraic relationships and the focus is on those which retain their reliability,
      even though the magnitudes of the structure factors contain experimental errors.
      The future utility of the algebraic relationships depends upon the development of
      suitable algorithms for solving them to obtain values for the unknown phases. One
      approach concerns a method for extending the range of least-squares calculations
      by modifying the defining equations without changing the global minima and by
      further altering the nature of the minimization function from time to time during
      the course of the least-squares calculation, while still preserving the global
      minima. The objective is to smooth the minimization function and alter the
      remaining false minima from time to time so that the minimization function is not
      trapped in a false minimum. Some calculations have been made that indicate the
      nature of the algebraic relationships among the phases and magnitudes and how the
      results of the calculations are benefited by having large values for the
      structure-factor magnitudes in the determinants.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7646838
TI  - Relationship of 13C NMR chemical shift tensors to diffraction structures.
AB  - 13C chemical shift tensor measurements on single crystals provide a powerful
      method to study changes in the electron environment of nuclei with changes in
      molecular structure. Thus, diffraction structures are critical to an
      understanding of chemical shift tensors. This work explores the general
      reliability of using structural data to predict components of the symmetrical
      chemical shift tensor. Imprecision in the hydrogen positions introduces
      considerable scatter in the simulated 13C shift tensors, and optimized C-H bond
      distances in methyl-beta-D-glucopyranoside used with the X-ray positions of the
      heavier C and O atoms greatly improve the simulated chemical shifts.
      Acenaphthene, with two crystallographically different molecules per unit cell,
      offers an excellent example for comparing and contrasting structural differences
      in the two molecules. A recently improved X-ray structure of naphthalene obtained
      at low temperature provides chemical shift simulations which are comparable to
      those from neutron diffraction methods and appear to reflect breaks in the D2h
      symmetry measured in the NMR chemical shift tensors. These data illustrate the
      close relationship between NMR and diffraction structures.

PMID- 7646839
TI  - Experimental evidence for the existence of non-nuclear maxima in the electron
      density distribution of metallic beryllium. A comparative study of the maximum
      entropy method and the multipole refinement method.
AB  - The electron-density distribution (EDD) of metallic beryllium has been derived
      from the structure factors of Larsen & Hansen [(1984). Acta Cryst. B40, 169-179]
      using the maximum entropy method (MEM). Subsequent topological analysis reveals
      non-nuclear maxima (NNM) in the EDD. Plots of the gradient field of the electron
      density illustrates this finding. A possible critical-point network for the
      hexagonal close-packed (h.c.p.) structure of beryllium is suggested. It is thus
      demonstrated that it is possible to obtain detailed topological information about
      the electron density in metallic beryllium without the use of a structural model.
      In order to test the findings of the MEM, the same set of structure factors were
      analysed using the multipole refinement method (MRM). Use of the MRM also reveals
      NNM. The results of the two different approaches to electron-density analysis are
      contrasted and discussed. Expressed within the framework of the theory of atoms
      in molecules, our results suggest that the h.c.p. structure of beryllium has no
      Be atoms directly bonded to other Be atoms. The structure is held together
      through a three-dimensional network of bonds between the NNM and Be atoms as well
      as between different NNM. The topological analysis thus reveals that the
      beryllium structure has important interactions connecting Be atoms of different
      basal plane layers. The breaking of these interactions when forming a surface may
      explain the abnormally large expansion of the inter-layer distance in the
      beryllium surface structure.

PMID- 7646840
TI  - Impairment of flow-dependent coronary dilation in hypertensive patients.
      Demonstration by cold pressor test induced flow velocity increase.
AB  - In normal coronary arteries, increased flow velocity induces endothelium
      dependent dilation, and dilation in response to sympathetic stimulation evoked by
      the cold pressor test is partly due to increased flow velocity. In arterial
      hypertension, angiographically normal coronary arteries were constricted by
      acetylcholine, an endothelium-dependent vasodilator. To assess the epicardial
      coronary artery response to the increase blood flow velocity induced by the cold
      pressor test in hypertensive patients with angiographically normal coronary
      arteries, coronary artery diameters and flow velocity were measured during cold
      pressor test in 12 untreated hypertensive patients and in 10 control subjects.
      Diameters were determined by quantitative angiography on proximal and distal
      segments of the left anterior descending coronary artery, and flow velocity
      measurements were made by Doppler testing in the distal segment. In control
      subjects, the proximal and distal segments dilated during cold pressor test by
      12.0 +/- 4.5% and 13.9 +/- 6.5%, respectively (both P < .001), when flow velocity
      increased by 46.7 +/- 26.1% (P > .05). In hypertensive patients, segments were
      constricted, respectively, by 10.3 +/- 8.5% (P < .001) and 7.9 +/- 8.6% (P <
      .01), when the flow velocity was increased by 68.3 +/- 48.2% (P < .001).
      Intracoronary injection of an endothelium-independent dilator resulted in similar
      dilation in control subjects (proximal: +30.0 +/- 12.9%; distal: +32.4 +/- 15.2%)
      and in hypertensive patients (proximal: +22.3 +/- 7.5%; distal: +28.8 +/- 15.4%).
      In conclusion, in hypertensive patients with angiographically normal coronary
      arteries and without any other coronary risk factors, endothelium-dependent flow
      mediated coronary dilation evoked by the cold pressor test is impaired.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7646841
TI  - Endothelium-derived hyperpolarizing factor(s) and the potentiation of kinins by
      converting enzyme inhibitors.
AB  - Inhibitors of angiotensin converting-enzyme (ACE) enhance the endothelium
      dependent relaxation to bradykinin and cause the accumulation of kinins in the
      vascular wall. Bradykinin elicits the production of vasodilator prostanoids and
      nitric oxide by endothelial cells. However, there is an additional component to
      the dilator actions of bradykinin, which is mediated by a diffusible endothelium
      derived hyperpolarizing factor (EDHF). The knowledge gathered on the nature of
      EDHF and its mechanism of action are reviewed briefly. EDHF causes
      hyperpolarization and relaxation of arterial smooth muscle by activating K(+)
      channel, the nature of which varies between species. During the inhibition of
      both cyclooxygenase and nitric oxide synthase, concentration-response
      relationships of the hyperpolarization and relaxation elicited by bradykinin
      overlap in canine coronary arteries. Both effects are enhanced equally by the ACE
      inhibitor perindoprilat. They are inhibited by membrane depolarization that is
      obtained by raising the extracellular concentrations of potassium ions. Likewise,
      in the human coronary artery, the hyperpolarization elicited by bradykinin, which
      is also mediated by EDHF, is augmented in the presence of perindoprilat and
      prevented by potassium-induced depolarization. In this blood vessel, contrary to
      the canine coronary artery, the EDHF-mediated responses occur at concentrations
      comparable to those initiating the nitric oxide-dependent component. Therefore,
      the increased production of EDHF, which is induced by kinins, may contribute to
      the cardiovascular effects of perindoprilat, together with an enhanced production
      of nitric oxide and vasodilator prostanoids.

PMID- 7646842
TI  - Endothelial cell signaling and endothelial dysfunction.
AB  - Endothelial cells have an important protective role in maintaining the normal
      physiologic function of the vascular wall. When these cells become dysfunctional,
      they lose this protective influence and they actively promote pathophysiological
      changes within the blood vessel. This review will discuss some of the
      extracellular signaling mechanisms employed by normal endothelial cells to exert
      a protective influence in the vascular wall and those signals generated by
      dysfunctional cells to promote the atherosclerotic process. It will also discuss
      the intracellular processes that regulate the release/expression of these signals
      and that control the transformation of this protective cell to one that promotes
      the development of vascular disease.

PMID- 7646843
TI  - Angiotensin converting enzyme inhibitors and endothelial dysfunction.

PMID- 7646844
TI  - Prevention of endothelial dysfunction in small and large arteries in a model of
      chronic heart failure. Effect of angiotensin converting enzyme inhibition.
AB  - Chronic heart failure (CHF) impairs endothelium-dependent vasodilatation of large
      conductance arteries. We investigated whether a similar reduction also occurs in
      small arteries, and whether such a reduction can be prevented by the angiotensin
      converting enzyme inhibitor perindopril (P) in a rat model of CHF (left coronary
      artery ligation). After 1 month treatment with placebo or P (2 mg/kg/day), rats
      were anesthetized and arterial pressure, left ventricular end-diastolic pressure,
      and central venous pressure were measured with a micromanometer. Segments of
      aorta and mesenteric artery (mean diameter, 281 +/- 8 microns) were then
      isolated, cannulated, and perfused at constant pressure using an arteriograph.
      Responses to increasing concentrations of acetylcholine (Ach), nitroprusside, and
      to 10(-4) mol/L NG-nitro-L-arginine methyl ester (L-NAME) were studied after
      preconstriction by phenylephrine. Heart failure resulted in a decrease in
      systolic and diastolic pressures, an increase in left ventricular end-diastolic
      and central venous pressures, and a significant depression of Ach-induced
      dilatation of the mesenteric artery (maximal dilatation, from 90 +/- 4% to 63 +/-
      4%, P < .05) but not of the aorta (from 56 +/- 8% to 45 +/- 5%, NS) without any
      modification in the endothelium-independent vasodilatation induced by
      nitroprusside. In the group treated by the angiotensin converting enzyme (ACE)
      inhibitor perindopril, systolic and diastolic pressures were slightly decreased,
      whereas left ventricular end diastolic, central venous pressures, and the
      endothelium-dependent vasodilating response to Ach were normalized. Responses to
      L-NAME were not affected by CHF or perindopril. Perindopril also decreased
      hypertrophy, as evidenced by a significantly lower heart weight in treated
      rats.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7646845
TI  - Antibody humanization predicted by computer graphic analysis.
AB  - Humanized antibodies continue to be evaluated in clinical trials, and each trial
      will yield valuable information for the design of the next generation of
      humanized antibodies. More attention will be given to the use of antibody
      fragments and the selection of human antibody specificities from phage libraries
      for human antibody therapeutics. Computer graphic analysis and molecular modeling
      of antibody structures will continue to be invaluable for predicting structural
      modifications for humanization of antibodies and for extracting structural
      information from antigen binding sites that can ultimately lead to small molecule
      therapeutics.

PMID- 7646846
TI  - Forensic applications of gel electrophoresis.

PMID- 7646847
TI  - Subtlety in control--metabolic pathway engineering.

PMID- 7646848
TI  - The genetic engineering of microbial solvent production.
AB  - Although the production of acetone and butanol by Clostridium strains was a
      thriving industrial fermentation process, it is no longer competitive with the
      chemical synthesis of solvents and has been discontinued. However, studies on the
      molecular biology of Clostridium strains suggest that genetic engineering for
      improved solvent production is feasible, and could result in the revival of the
      industrial fermentation process.

PMID- 7646849
TI  - Signal transduction and secondary metabolism: prospects for controlling
      productivity.
AB  - Evidence is accumulating that demonstrates the key roles played by diffusible
      molecules in regulating cellular differentiation, even among prokaryotic
      microorganisms. This is exemplified by A-factor and its analogues, which act as
      autoregulators for morphological differentiation and secondary metabolism in
      Streptomyces. The identification of a specific receptor for A-factor and an A
      factor-controlled promoter sequence in S. griseus indicate the close similarity
      of this system to eukaryotic hormonal control. The involvement of prokaryotic
      homologues of the eukaryotic Ser/Thr-kinases in the regulation of differentiation
      processes seems to be another characteristic feature of this group of bacteria.
      Recent evidence for the presence of these molecular signalling systems in
      Streptomyces is reviewed, along with the inherent implications.

PMID- 7646850
TI  - Unique peptide modifications involved in the biosynthesis of lantibiotics.
AB  - The lantibiotics are a unique class of bacterium-derived peptide antibiotics, all
      of which contain the rare amino acid lanthionine, as well as a number of other
      nonprotein amino acids. Unlike most other peptide antibiotics, lantibiotics are
      produced on the ribosome as a prepeptide, and a series of post-translational
      modifications converts this precursor into the biologically active peptide. A
      complex set of gene products involved in lantibiotic biosynthesis have been
      identified, including the genes for specific amino acid modifications, as well as
      other ancillary biosynthetic functions. In the future, it should be possible to
      use some of these enzymes to engineer novel, non-protein amino acids into other
      proteins of biotechnological interest and importance.

PMID- 7646851
TI  - Significance of DNA ploidy in the treatment of T1 glottic carcinoma.
AB  - OBJECTIVE: To assess the role of DNA ploidy as a predictor of radioresistance in
      T1 glottic carcinoma. DESIGN: Case-control study. Flow cytometric DNA ploidy
      measurements were performed on formalin-fixed paraffin-embedded tumor specimens
      from 15 patients with T1 glottic laryngeal carcinomas in whom radiotherapy had
      failed and from a matched group of 15 patients in whom an identical radiotherapy
      regimen was curative. Analysis of DNA content was performed blind to outcome of
      treatment. SETTING: Academic tertiary referral medical center. PARTICIPANTS:
      Thirty patients with clinically staged T1, N0, M0 glottic carcinoma.
      INTERVENTION: All patients received radiation to the larynx through opposed
      lateral ports at a total dose of 64 to 70 Gy. RESULTS: Ten diploid and five
      aneuploid histograms were found in the resistant group, and six diploid and nine
      aneuploid histograms were found in the radiosensitive group. This difference was
      not statistically significant. A trend toward a higher relapse rate after
      radiotherapy (62.5%) among patients with diploid tumor compared with those with
      aneuploid tumor (35.7%) was noted. CONCLUSIONS: DNA ploidy did not predict
      response to radiotherapy in patients with T1 glottic cancer, probably because of
      the small number of patients. A trend toward lower risk of local recurrence after
      radiotherapy in aneuploid tumors was noted. A larger prospective study is needed
      to assess the value of DNA ploidy in the treatment of early laryngeal cancer.

PMID- 7646853
TI  - Inhibition of growth of a murine squamous cell carcinoma by a cyclooxygenase
      inhibitor increases leukotriene B4 production.
AB  - OBJECTIVE: To determine the role of metabolites of arachidonic acid in the growth
      of squamous cell carcinomas of the head and neck. DESIGN: Investigation of the
      effect of a cyclooxygenase inhibitor, piroxicam, on the growth of squamous cell
      carcinoma in a murine model. INTERVENTION: C3H/HeJ mice bearing squamous cell
      carcinoma (SCCVII) were treated with piroxicam (0.08 mg/d, orally) for 30 days
      beginning 1 day before tumor inoculation. MAIN OUTCOME MEASURES: Decrease in
      tumor volumes and tumor growth rates. RESULTS: Significant inhibition of tumor
      growth (P = .002) and final tumor weight (P = .0007) was noted in the group
      receiving piroxicam therapy. Prostaglandin E2 levels in the tumor tissue were
      unrelated to treatment or tumor size. Increased levels of leukotriene B4 were
      observed in the piroxicam-treated group (P = .03), and larger tumors were
      associated with decreased leukotriene B4 levels (P = .0001). CONCLUSIONS:
      Cyclooxygenase inhibitors may be effective in the treatment of some squamous cell
      carcinomas. The therapeutic effect of cyclooxygenase inhibitors may result from
      shunting into the lipoxygenase pathway of arachidonic acid metabolism.

PMID- 7646852
TI  - Heat shock enhances the susceptibility of tumor cells to lysis by lymphokine
      activated killer cells.
AB  - OBJECTIVE: To determine whether heat-treated thyroid cancer cells augment the
      susceptibility of target cells to lysis by autologous lymphokine-activated killer
      cells. DESIGN: Peripheral blood lymphocytes from patients with thyroid cancer
      were incubated with recombinant interleukin 2 (100 U/mL) for 7 days, and thyroid
      cancer cells obtained from surgical specimens were heated at 44 degrees C for 20
      minutes and incubated at 37 degrees C for 18 hours before performing the
      radioactive chromium Cr 51 release assay. RESULTS: The susceptibility of heat
      treated thyroid cancer cells to lysis by autologous and allogeneic lymphokine
      activated killer cells was significantly greater than that of untreated tumor
      cells. The mechanism of enhanced susceptibility was unclear. However, the effect
      depended on de novo protein synthesis, because inhibition of RNA synthesis by
      dactinomycin completely abolished the heat-enhanced susceptibility of tumor
      cells. CONCLUSION: Immunotherapy combined with hyperthermia may be useful in
      management of thyroid cancer.

PMID- 7646854
TI  - Therapeutic implications in the treatment of aural Pseudomonas infections based
      on in vitro susceptibility patterns.
AB  - OBJECTIVE: To examine the in vitro susceptibility patterns of aural isolates of
      Pseudomonas aeruginosa and to identify changes over a 4-year period. DESIGN:
      Retrospective case series. SETTING: The outpatient department at Children's
      Hospital of Pittsburgh (Pa), a tertiary referral center. PATIENTS: Ambulatory
      children younger than 18 years from whose ears P aeruginosa was isolated. OUTCOME
      MEASURES: The in vitro susceptibility of aural isolates of P aeruginosa to
      ampicillin, cefotaxime, chloramphenicol, sulfisoxazole, ticarcillin, mezlocillin,
      gentamicin, tobramycin, cefazolin, tetracycline, piperacillin, nitrofurantoin,
      cephalexin hydrochloride, ceftriaxone, cefuroxime axetil, and sulfamethoxazole
      trimethoprim. RESULTS AND CONCLUSIONS: No changes were found in the trends of the
      susceptibility patterns over the 4-year study period, with the exception of the
      semisynthetic penicillins, ticarcillin and mezlocillin. These two agents were
      found to be relatively ineffective against the strains of P aeruginosa isolated
      in 1989 (59% and 18% susceptibility, respectively). This finding is in contrast
      to their effectiveness over the remainder of the study period (96% and 90%
      susceptibility, respectively), which was excellent. These observations likely
      reflect a change in the breakpoints for the minimal inhibitory concentrations
      between these periods. The intravenous agent with the best susceptibility profile
      was piperacillin (96%). Of the aminoglycosides tested, 94% of the isolates were
      sensitive to tobramycin, as opposed to only 79% for gentamicin. This finding may
      have significance when one is empirically selecting ototopical therapy, since
      both tobramycin and gentamicin are available as topical preparations. Of the oral
      agents, the combination of sulfamethoxazole-trimethoprim was most effective
      (46%).

PMID- 7646855
TI  - Internal carotid artery resection for invasion of malignant tumors.
AB  - BACKGROUND: To study the preoperative investigation and outcome of patients who
      underwent resection of the internal carotid artery for malignant disease. A
      retrospective analysis using a chart review of these patients was performed, and
      the results were analyzed. All patients were treated by one of us (U.K.N.) at the
      University of California-Davis Medical Center, Sacramento. A population of 18
      patients who underwent a transcervical, transpetrosal, or petrocavernous
      resection of the internal carotid artery from 1976 to 1993 was studied.
      Preoperative study consisted of four-vessel arteriography, balloon test
      occlusion, electroencephalographic intraoperative monitoring, and, after 1990,
      single-photon emission computed tomographic scanning. Disease-free interval and
      neurologic complications were assessed. RESULTS: Two patients were alive and well
      without disease at 6 and 9 months postoperatively. One patient was alive and well
      at 12 months, and three have survived more than 2 years without recurrent tumor.
      Eleven patients died within 1 year of surgery (three postoperatively, six of
      recurrent disease, and two of unknown causes). One patient died of disease at 14
      months. CONCLUSIONS: Internal carotid artery invasion by malignancy portends a
      poor prognosis. Carotid artery resection can provide reasonable palliation. Early
      results of skull-base surgery on patients with intrapetrous and petrocavernous
      carotid artery involvement are encouraging. Balloon test occlusion and single
      photon emission computed tomographic scanning provide a valuable assessment of
      contralateral cerebral blood flow.

PMID- 7646856
TI  - Laryngeal manifestations of epidermolysis bullosa acquisita.
AB  - Epidermolysis bullosa acquisita is an acquired blistering skin disease caused by
      autoantibodies to the dermoepidermal junction of the skin. Patients present with
      tense bullae over areas of trauma, commonly the palms, soles, elbows, and knees.
      When the lesions heal, they leave a dense scar. In the head and neck, bullae in
      the buccal mucosa and the cervical esophagus cause strictures. To our knowledge,
      this is the first reported case of epidermolysis bullosa acquisita of the larynx.
      The patient had severe supraglottic stenosis that was caused by the trauma of a
      routine intubation. We describe the clinical and histologic characteristics of
      the disease and suggest managing the strictures with balloon dilation to minimize
      trauma and prevent further lesions and scarring.

PMID- 7646858
TI  - Metastatic melanoma to the cerebellopontine angle. Clinical and imaging
      characteristics.
AB  - OBJECTIVE: To describe the clinical and imaging features of metastatic melanoma
      to the cerebellopontine angle (CPA). DESIGN: A case series study with world
      literature review. SETTING: House Ear Clinic and St Vincent's Hospital, Los
      Angeles, Calif. PATIENTS: Three cases of metastatic CPA tumors operated on at the
      House Ear Clinic. INTERVENTIONS: All patients underwent surgical removal of CPA
      metastatic melanoma. MAIN OUTCOME MEASURE: Survival and duration of disease-free
      interval are reported. RESULTS: Two patients died of melanoma within 5 months of
      diagnosis and resection of CPA melanoma metastases. One patient survived for 5
      years after undergoing total resection of an isolated CPA melanoma metastasis.
      Magnetic resonance imaging features were not uniform. CONCLUSIONS: Metastatic
      melanoma to the CPA should be suspected in patients with a history of melanoma
      and a rapid progression of audiovestibular or facial nerve symptoms. Surgical
      removal of solitary metastases to the CPA may be valuable in patients without
      other melanoma focus; however, the long-term prognosis for patients with CPA
      melanoma is grim.

PMID- 7646857
TI  - Nasal inverted papilloma with involvement of middle ear and mastoid.
AB  - Inverted papillomas of the paranasal sinuses have been characterized by their
      unusually benign histologic features, their ability to grow rapidly with bony
      destruction, and their tendency to recur if not adequately treated. The
      association of inverted papilloma with squamous cell carcinoma is well described,
      but malignant transformation is relatively rare. We report a case of a multiply
      recurrent inverted papilloma that spread to the middle ear and mastoid and
      eventually underwent malignant transformation with skull base invasion.
      Pathologic examination demonstrated many of the characteristics associated with
      malignant transformation. In addition, progesterone receptors were demonstrated
      that may have stimulated this tumor during the patient's pregnancy. To our
      knowledge, no similar cases have been reported in the literature.

PMID- 7646859
TI  - Pathologic quiz case 1. Granular cell tumor (GCT) of larynx.

PMID- 7646860
TI  - Pathologic quiz case 2. Synovial sarcoma of the hypopharynx.

PMID- 7646861
TI  - Asystole during thyroid resection.

PMID- 7646862
TI  - Ear candles.

PMID- 7646863
TI  - Free forearm flap in oral reconstruction. Functional outcome.
AB  - OBJECTIVE: To examine functional outcome associated with free radical forearm
      flap reconstruction of oral cavity and oropharyngeal defects. DESIGN AND SETTING:
      Case series obtained from a head and neck clinic conducted at a regional cancer
      center. Patients underwent surgery at the associated tertiary care center.
      PATIENTS: Thirty consecutive patients treated for oral and oropharyngeal
      malignant neoplasms staged from T1 to T4 were studied. Subjects were assigned to
      five groups based on the site and extent of their surgical resections, as
      specified on a resection template. INTERVENTION: All patients had undergone free
      radial forearm flap reconstruction of their surgical defects. OUTCOME MEASURES:
      Ten factors reflecting functional properties and processes of the upper
      aerodigestive tract were evaluated clinically or with videofluoroscopy or both.
      RESULTS: Near-normal and fair oral and oropharyngeal function wholly
      characterized the sample. Patients who underwent reconstruction of unilateral
      tongue, floor of mouth-ventral tongue, and retromolar trigone-buccal defects
      functioned well on most measures; the function of patients with anterior tongue
      jaw and tongue base-tonsil defects varied. CONCLUSIONS: Functional outcome with
      free radial forearm flap reconstruction was favorable for three of five subgroups
      of oral and oropharyngeal cancer patients. Qualitatively different functional
      profiles emerged for subgroups based on resection site. Methodologic issues for
      research on surgical reconstruction and functional outcome include the need for a
      meaningful, reliable system of classifying oral and oropharyngeal resections, and
      the development of standardized procedures for evaluating functional outcome.

PMID- 7646864
TI  - Sensory recovery in noninnervated flaps used for oral cavity and oropharyngeal
      reconstruction.
AB  - OBJECTIVES: To assess the clinical recovery of sensation in noninnervated flaps
      used for oral cavity and oropharyngeal reconstruction. To correlate the return of
      flap sensation to articulation and swallowing. DESIGN: Prospective nonrandomized
      study. Six months minimum follow-up. SETTING: Tertiary care center. PATIENTS:
      From April 1, 1991, to May 31, 1993, 12 patients underwent resection of stage III
      or greater squamous cell carcinoma of the oral cavity or oropharynx. Ten patients
      were previously untreated; two had failed previous full-course radiation therapy.
      Reconstruction was performed with either a pedicled musculocutaneous flap (four
      patients) or a fasciocutaneous free flap (eight patients). Flap sensation to
      touch, sharp vs dull, two-point discrimination, and warm vs cold was evaluated in
      each of these patients at monthly intervals by two independent observers. In
      addition, an extensive evaluation of articulation and swallowing was performed on
      all 12 patients a minimum of 6 months after surgery. 10 patients (83%) (eight of
      eight with fasciocutaneous free flaps and two of four with musculocutaneous
      flaps), with a strong trend for sensory recovery with the fasciocutaneous free
      flaps over the musculocutaneous flaps (P = .09). Sensory recovery correlated
      statistically with articulation (P = .045) and oral intake (P = .045). Patients
      who underwent reconstruction of base of tongue defects had significantly worse
      articulation and swallowing than those who underwent reconstruction of other
      sites (P = .04). No statistically significant correlation was found between
      patient age, flap size, history of irradiation, or length of follow-up (> 6
      months) and flap sensation, articulation, or swallowing. CONCLUSIONS: Spontaneous
      return of flap sensation was documented by clinical testing in the majority (83%)
      of patients who underwent reconstruction of oral cavity or oropharyngeal defects
      with noninnervated flaps. Sensory recovery occurred more often in patients with
      fasciocutaneous free flaps (100%) than in those with musculocutaneous flaps
      (50%). Articulation and swallowing correlated statistically with the return of
      flap sensation.

PMID- 7646865
TI  - Chemoradiotherapy for organ preservation in oral and pharyngeal carcinoma.
AB  - OBJECTIVES: To use concurrent chemoradiotherapy as primary treatment for
      resectable head and neck squamous cell carcinoma to (1) demonstrate the
      feasibility of an organ preservation approach for nonlaryngeal sites; (2)
      evaluate the toxic reactions and response to a new combination of two platinum
      compounds; and (3) monitor the effect of therapy on oral and pharyngeal function.
      DESIGN: Case series, a prospective single-armed trial. SETTING: Tertiary referral
      center. PATIENTS: Twenty-two patients with head and neck squamous cell carcinoma
      of the oral cavity, oropharynx, and hypopharynx for whom surgery would
      significantly compromise function were entered in this trial. INTERVENTION:
      Standard fractionation external-beam radiation therapy (2 Gy/Fx; total, 70 Gy)
      was given during a 9-week period, including a 2-week break after 40 Gy,
      concurrently with eight weekly doses of carboplatin and three doses of cisplatin
      (100 mg/m2) at 3-week intervals. A biopsy was performed 12 weeks after the
      completion of chemoradiotherapy to assess clinical response. All patients
      presenting with nodes greater than 3 cm had planned neck dissection. MAIN OUTCOME
      MEASURES: Tumor response, toxic reactions, survival, and oral and pharyngeal
      function. RESULTS: Overall complete response was 86%. Estimated overall 2-year
      survival was 64%, and disease-specific survival was 71% (median follow-up time,
      25 months). Five patients have died of disease and two of unrelated causes.
      Treatment was completed by all, with toxic reactions including myelosuppression,
      mucositis, and dysphagia. Half of the patients required gastrostomy. CONCLUSIONS:
      Concurrent chemoradiotherapy using two platinum analogues was tolerated with good
      local control and survival. Notable dysphagia was common. This study provides
      pilot data for randomized clinical trials to confirm the usefulness of
      chemoradiotherapy for nonlaryngeal organ preservation.

PMID- 7646867
TI  - Transclavicular approach to the neck, thoracic inlet, and axilla.
AB  - OBJECTIVE: To describe claviculotomy and claviculectomy for access to lesions of
      the lower part of the neck, with simultaneous reconstruction. METHODS AND
      MATERIALS: A retrospective review of 15 patients who underwent claviculotomy for
      access to the lower part of the neck. RESULTS: Eight patients underwent plate
      reconstruction, and one patient required subsequent removal. Three patients
      underwent total claviculectomy, and four patients underwent partial
      claviculectomy. Ten patients are alive and free of disease, three have died of
      disease, and two are alive with disease. All but two patients are satisfied with
      shoulder function, and one patient is dissatisfied with the cosmetic result.
      CONCLUSIONS: The claviculotomy and claviculectomy technique for tumors that
      transgress the neck, thoracic inlet, and axilla offers maximal exposure for
      excision, vascular control, and preservation of vital structures. Modern plating
      techniques have allowed clavicular reconstruction with improved cosmesis and
      preservation of shoulder stability.

PMID- 7646866
TI  - Drains in thyroid and parathyroid surgery. Are they necessary?
AB  - OBJECTIVE: To assess the postoperative complications in patients who underwent
      elective thyroid or parathyroid surgery without postoperative drainage. DESIGN:
      During a 6-year period all patients who met study criteria were prospectively
      evaluated. SETTING: General community and tertiary referral center. PATIENTS:
      Fifty-seven patients undergoing thyroid surgery and eight patients undergoing
      parathyroid surgery were evaluated. Twenty-four patients were excluded because
      drains were placed postoperatively. Reasons for exclusion included presence of a
      large dead space, substernal goiter, extensive neck dissection for malignant
      neoplasm, and large goiters. RESULTS: Major complications consisted of a hematoma
      requiring reexploration in one patient, and a recurrent nerve palsy in one
      patient. Minor complications consisted of temporary hypocalcemia (three), seroma
      (one), and superior flap edema that resolved in 3 months (20). CONCLUSION:
      Routine prophylactic drainage in a select patient population is unnecessary after
      uncomplicated thyroid or parathyroid surgery.

PMID- 7646868
TI  - Nonsurgical alternative therapy for bulky advanced head and neck tumors.
AB  - OBJECTIVE: To rapidly induce symptomatic relief and local tumor control in bulky
      advanced head and neck tumors without surgery. DESIGN: A retrospective analysis
      of the results with palladium 103-labeled or iodine 125-labeled brachytherapy
      (BT) and adjunctive external beam radiation therapy (EBRT); a survival analysis
      by the Kaplan-Meier method; and a comparison of results between the BT/EBRT and
      EBRT/BT (or BT alone) groups by the log-rank test. A nonsurgical alternative
      therapy was given to a total of 51 patients who presented with tumors of more
      than 100 cm3 in volume. RESULTS: Moderate to complete symptomatic relief was
      observed in 31 (61%) of 51 patients. Seven (33%) of 21 patients in the BT/EBRT
      group and two (7%) of 30 in the EBRT/BT group were recurrence-free at 36 months.
      The difference was significant by the log-rank test. Cause-specific and overall
      36-month survivals were 23% and 5%, respectively. CONCLUSION: Cure rate by
      conventional therapy in bulky advanced head and neck tumors is dismal. The
      palladium 103- or iodine 125-BT/EBRT offers good symptomatic relief and an
      acceptable probability of recurrence-free survival.

PMID- 7646869
TI  - Treatment of ameloblastoma of the jaws.
AB  - OBJECTIVE: To evaluate treatment of ameloblastoma of the jaws and suggest a more
      aggressive approach for well-defined cases. SETTING: Referral center. PATIENTS:
      Forty-one patients were treated for ameloblastoma of the jaws. RESULTS: Seventeen
      patients had a local recurrence; 14 had initial curettage and three had initial
      resection. Seven patients had two or more recurrences. Eight patients underwent
      radiotherapy; two died of progressive disease. CONCLUSIONS: Ameloblastoma had a
      high rate of local recurrence if not adequately removed. Segmental resection for
      the mandible and partial maxillectomy for the maxilla should be the primary
      treatment; marginal resection is appropriate only for small primary tumors. For
      multiple recurrences, radiotherapy is effective, and surgery and radiotherapy (50
      Gy postoperatively) should be used in selected cases.

PMID- 7646870
TI  - Photodynamic therapy for recurrent nasopharyngeal cancer.
AB  - OBJECTIVE: A pilot study to determine if photodynamic therapy could be a safe and
      efficacious treatment for recurrent or persistent nasopharyngeal cancer. DESIGN:
      A consecutive sample intervention study with comparison with historic control
      subjects. SETTING: Tertiary referral hospital. PATIENTS: All patients with
      recurrent or persistent nasopharyngeal cancer following radiation therapy were
      considered for treatment. Patients with tumors with a depth of more than 10-mm
      invasion on computed tomographic scans were excluded, as were patients with
      recurrent metastasis to the neck. Five patients were thus acquired during a 3
      year period. INTERVENTION: Four patients were injected intravenously with
      hematoporphyrin derivative (2.5 mg/kg) and one patient with porfimer sodium (2
      mg/kg) (Photofrin, Quadra Logic Technologies, Vancouver, British Columbia) 48
      hours before treatment. The drug was activated by a 630-nm laser light passed
      down a 1-mm core quartz fiber to a miniaturized convex mirror positioned in the
      nasopharynx via the contralateral nasal cavity. This procedure was carried out
      under topical anesthesia. MAIN OUTCOME MEASURE: Survival was determined after a
      minimum follow-up of 4 years. RESULTS: To date, three of five patients treated
      have no evidence of disease, with follow-up times of 51, 52, and 60 months,
      respectively. The patient with the longest survival time had been unsuccessfully
      treated with 136 Gy of ionizing radiation preceding photodynamic therapy.
      CONCLUSIONS: Long-term tumor control can be achieved by photodynamic therapy in
      cases where very high doses of ionizing radiation have failed. The entire
      treatment can be accomplished in 30 minutes under topical anesthesia. The
      technique carries no serious side effects.

PMID- 7646872
TI  - Study of a regional circulatory system based on the "equivalent tube" concept:
      the feto-placental circulation.
AB  - The fluid-dynamical description of a regional circulatory system, based on the
      numerical solution of the dynamical equations applied to an equivalent tube is
      proposed. The feto-placental circulation is explicitly studied with this
      technique as an example, and results are discussed and compared with experimental
      data. The original features of this work are the quantitative description of the
      terminal load of the vascular system on the basis of morphological data and the
      attention paid to the formulation of physiologically sensible boundary conditions
      for the dynamical equations.

PMID- 7646873
TI  - In vitro viability of vitrified mouse morulae thawed at different temperatures.
AB  - The effect of thawing temperature on in vitro development of vitrified mouse
      morulae was investigated. The embryos were vitrified in a solution based on
      ethylene glycol as cryoprotectant, and Ficoll as macromolecule to assist
      vitrification. They were then thawed at 20 degrees, 37 degrees and 48 degrees C
      for 6 sec and at 48 degrees C for 2 sec. Among groups, there was no significant
      difference on the development at 72 h of culture when embryos were thawed at 20
      degrees, 37 degrees C for 6 sec or 48 degrees C for 2 sec. At 48 h of culture the
      embryos thawed at lower temperature had a reduced resumption (69.5%) while the
      embryos thawed at 37 degrees and 48 degrees C for 2 sec had a higher resumption
      rate (80.0% and 82.5%). It was concluded that a high development in vitro of
      vitrified mouse morulae can be obtained at three different temperatures of
      thawing, although at higher temperatures there seems to be a tendency of an
      earlier resumption development.

PMID- 7646871
TI  - Bone mineral density across the normal rat femour.
AB  - The post-ovariectomy osteoporotic rat model is widely used to mimic post
      menopausal human osteoporosis and to test the efficacy of the therapies used in
      its treatment An experimental study was performed in order to improve the
      reliability of bone mineral density (BMD) measurements by correcting also the
      relocation error. In addition, a BMD map of the whole femur was carried out to
      detect the areas of uniform density, where the reliability of measuring was
      improved. Right femurs were taken from 5 Sprague Dawley female rats, 10 months
      old, and tested every 2 mm from the supracondylar line to the peritrochanteric
      line (6 scans for each site). Repositioning error was tested for each site of
      measurement, and measurements done by 3 different operators in a double blind
      test were compared. At site 4 and 24 (where the differences are high) and site 10
      (where the differences of BMD are low) the coefficient of variability (CV) was
      calculated repositioning the bone after each measurement scan for a total of 6
      scans. The CV at sites 4 and 24 were significantly higher than at site 10 (p <
      0.05). In our opinion, the bone segment between 8 and 14 mm from the
      supracondylar line is that which presents the highest homogeneity and where it is
      preferable to perform the measurements in order to obtain the maximum effect of
      the method (improvement of precision of about 30%) in comparison with the other
      femur sites tested.

PMID- 7646874
TI  - Protein kinase C (PKC) isoenzymes exhibit specific expression in the vertebral
      column of human fetuses.
AB  - Recent studies have shown that protein kinase C (PKC) plays a pivotal role in
      many cellular functions, i.e. cell proliferation and differentiation, exocytosis,
      ion-exchange regulation, hormone and neurotransmitter release, programmed cell
      death. Up to now the tissue and organ distribution of PKC isoenzymes have been
      studied in various mammalian adults and it has been suggested that each of them
      could play a specific role in the regulation of various cellular functions.
      However, few works have been performed on the expression of the enzyme in
      actively proliferating and differentiating tissues, i.e. during embryonal and
      fetal developmental stages. In the present study we have performed an
      immunohistochemical analysis by using polyclonal antibodies in order to verify
      the distribution of nine PKC isoenzymes in the vertebral column of human fetuses
      in a key period (8th developmental week), when the most relevant chondrogenetic
      and osteogenetic processes occur. The detection of the various PKC isoenzymes and
      their different distribution in the vertebral bodies and in the intervertebral
      spaces lead to speculate that the appearance, localization and activation of PKC
      isoforms in chondrocytes might depend on the stage of chondrogenesis and suggest
      that cartilage and developing bone represent an appropriate cell system to
      understand the mechanism of signal transduction, which involves the enzyme.

PMID- 7646875
TI  - Cultured tibial rat osteoblasts: in vitro production and topography of
      osteonectin, biglycan and decorin.
AB  - Rat osteoblasts in culture undergo differentiative changes culminating in the
      formation of mineralized foci. We here report on the pattern of temporal
      expression and compartmentalization of osteonectin and of the two small
      proteoglycans, byglican and decorin. They were constitutively synthesized during
      in vitro differentiation of rat osteoblasts. The 3 proteins were detected in the
      conditioned medium and associated with the cell-matrix compartment. Within this
      compartment they showed prevalent cytoplasmic location and differential
      distribution on unmineralized noduli was detected for osteonectin and byglican,
      while decorin was detected throughout the nodules. Along with known functions in
      the matrix, a possible role in the cytoplasm may have to be sought for these bone
      cells components.

PMID- 7646876
TI  - Vitro drug-induced apoptosis in freshly isolated leukemic cells: a flow
      cytometric analysis.
AB  - Fludarabine is considered a useful drug in the management of B-CLL resistant to
      conventional chemotherapy as it is able to trigger apoptosis in neoplastic B
      cells. In order to analyze this aspect, we tested by means of a simple and rapid
      flow cytometric method the in vitro apoptotic response of CD5+ B-CLL lymphocytes
      to FAMP, in comparison with other cytoreductive agents such as Interferons. Our
      findings showed that apoptosis occurred significantly in lymphocytes cultured
      with FAMP, but not with IFNs. In conclusion, flow cytometry allows an easy and
      rapid detection of in vitro drug-induced apoptosis, possibly representing also a
      reliable assay for testing tumor cell sensitivity or resistance.

PMID- 7646877
TI  - Characterization of the subunits in an apparently homogeneous subpopulation of
      Clostridium thermocellum cellulosomes.
AB  - Clostridium thermocellum cellulosomes isolated by cellulose affinity
      chromatography were fractionated by anion exchange chromatography into apparently
      homogeneous subpopulation that differed with respect to enzyme activity and
      subunit composition. One such subpopulation contained predominantly six subunits
      and was closely similar to the "subcellulosome" described by Kobayashi et al.
      (Kobayashi, T., Romaniec, M. P. M., Fauth, U., and Demain, A. L., Appl. Environ.
      Microbiol., 1990, 56, 3040-3046). Avicelase specific activity of this homogeneous
      subpopulation was slightly higher than that of unfractionated cellulosomes, but
      the two preparations were similarly affected by Ca2+, dithiothreitol, and
      cellobiose. Determination of their N-terminal sequences and enzyme activities has
      enabled three of the six major subunits of the subpopulation of cellulosomes to
      be positively identified as known components of the C. thermocellum cellulase
      complex; the other three subunits did not match up with previously characterized
      cellulosomal proteins.

PMID- 7646878
TI  - Aspartic proteinase from Penicillium camemberti: purification, properties, and
      substrate specificity.
AB  - An acid proteinase from the culture filtrate of Penicillium camemberti was
      isolated in a two-step purification procedure by cation exchange chromatography
      and gel filtration. The enzyme is an aspartic proteinase inhibited by pepstatin,
      DAN, and EPNP, with a molecular mass determined by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis of 33.5 kDa. The optimum activity for
      hydrolysis of denatured hemoglobin is around pH 3.4. The enzyme is highly
      specific for the aromatic and hydrophobic amino acid residue in insulin B-chain
      and, like pepsin, selectively splits only one Leu7-Met8 peptide bond in the
      squash trypsin inhibitor CMTI 1. The hydrolyzed bond can be resynthesized by P.
      camemberti proteinase at neutral pH.

PMID- 7646879
TI  - Engineering resistance to trypsin inactivation into L-asparaginase through the
      production of a chimeric protein between the enzyme and a protective single-chain
      antibody.
AB  - We have demonstrated that a trypsin sensitive enzyme such as L-asparaginase can
      be rendered trypsin resistant by genetically fusing its gene with that of a
      single-chain antibody derived from a preselected monoclonal antibody capable of
      providing protection against trypsin. The chimeric L-asparaginase retained 75% of
      its original activity upon exposure to trypsin, whereas the native unprotected L
      asparaginase control was totally inactivated.

PMID- 7646880
TI  - Cloning, expression and characterization of a single-chain antibody fragment to
      the herbicide paraquat.
AB  - New cost effective methods for the detection and removal of pesticides from water
      samples are required to meet modern safety standards. The recent development of
      techniques to produce antibody fragments in bacteria has provided the opportunity
      to exploit antibodies as specialized chemicals for affinity detection/removal
      technologies. The variable heavy and light polypeptide chains of the anti
      paraquat monoclonal antibody PQXB1/2 have been cloned into the single-chain
      antibody (ScAb) expression vector pBG1. The construct was expressed in
      Escherichia coli and 0.4 mg functional antibody produced from 1 dm3 of induced
      culture. Characterization of ScAb by antigen binding profile and competition
      ELISA showed it to have a sensitivity one order of magnitude below that of the
      parent monoclonal. ScAb was purified as a monomer or dimer and analysed by HPLC
      size exclusion chromatography. When immobilized on polystyrene beads the ScAb
      could remove 85% of a paraquat-bovine serum albumin conjugate from solution in a
      single step.

PMID- 7646881
TI  - From tags to RAGS: chemoaffinity finally has receptors and ligands.

PMID- 7646882
TI  - Drosophila mushroom body subdomains: innate or learned representations of odor
      preference and sexual orientation?

PMID- 7646883
TI  - bFGF, neurotrophins, and the control or cortical neurogenesis.

PMID- 7646884
TI  - Restricted expression of the irreC-rst protein is required for normal axonal
      projections of columnar visual neurons.
AB  - The 104 kDa irreC-rst protein, a member of the immunoglobulin superfamily,
      mediates homophilic adhesion in cell cultures. In larval optic chiasms, the
      protein is found on recently formed axon bundles, not on older ones. In
      developing visual neuropils, it is present in all columnar domains of specific
      layers. The number of irreC-rst-positive neuropil stratifications increases until
      the midpupal stage. Immunoreactivity fades thereafter. The functional importance
      of the restricted expression pattern is demonstrated by the severe projection
      errors of axons in the first and second optic chiasms in loss of function mutants
      and in transformants that express the irreC-rst protein globally. Epigenesis of
      the phenotypes can be explained partially on the bases of homophilic irreC-rst
      interactions.

PMID- 7646885
TI  - Mutations that affect the length, fasciculation, or ventral orientation of
      specific sensory axons in the Drosophila embryo.
AB  - In wild-type Drosophila embryos, five lateral chordotonal (lch) axons in each
      abdominal hemisegment originate from a midlaterally positioned cluster of neurons
      and grow, fasciculate, and orient ventrally as they connect with targets in the
      CNS. We have identified 22 recessive lethal mutations in 12 complementation
      groups, 8 of which are novel, that differentially affect lch axon growth,
      fasciculation, or ventral orientation. Mutations in 3 loci result in shorter, but
      fasciculated and ventrally directed axon bundles. Mutations in 4 complementation
      groups cause lch axon defasciculation. Mutations in 7 complementation groups
      cause some lch axon bundles to grow dorsally along a trajectory 180 degrees from
      normal.

PMID- 7646886
TI  - The limbic system-associated membrane protein is an Ig superfamily member that
      mediates selective neuronal growth and axon targeting.
AB  - The formation of brain circuits requires molecular recognition between
      functionally related neurons. We report the cloning of a molecule that
      participates in these interactions. The limbic system-associated membrane protein
      (LAMP) is an immunoglobulin (Ig) superfamily member with 3 Ig domains and a
      glycosyl-phosphatidylinositol anchor. In the developing forebrain, lamp is
      expressed mostly by neurons comprising limbic-associated cortical and subcortical
      regions that function in cognition, emotion, memory, and learning. The unique
      distribution of LAMP reflects its functional specificity. LAMP-transfected cells
      selectively facilitate neurite outgrowth of primary limbic neurons. Most
      striking, administration of anti-LAMP in vivo results in abnormal growth of the
      mossy fiber projection from developing granule neurons in the dentate gyrus of
      the hippocampal formation, suggesting that LAMP is essential for proper targeting
      of this pathway. Rather than being a general guidance cue, LAMP likely serves as
      a recognition molecule for the formation of limbic connections.

PMID- 7646887
TI  - Systematic widespread clonal organization in cerebral cortex.
AB  - Cell lineage analysis in the cortex has revealed two clonal patterns, clustered
      and widespread clones. To determine the relationship of these patterns,
      progenitor cells were infected with a retroviral library encoding alkaline
      phosphatase, and cortical sibling cells were identified using PCR. Clones labeled
      at E15 consisted of single cells or small cells clusters (52%) or of widespread
      cells (48%). However, widespread clones consisted of multiple neuronal or glial
      cell types, spaced systematically at 2-3 mm intervals. The data suggest that
      migratory multipotential progenitors divide asymmetrically at intervals defined
      by cell cycle length, producing single cells or clusters of cells in different
      cortical regions. Transition from multipotentiality to more restricted potential
      may correspond to changes in migratory behavior.

PMID- 7646888
TI  - Radial and horizontal deployment of clonally related cells in the primate
      neocortex: relationship to distinct mitotic lineages.
AB  - To analyze cell lineage in the rhesus monkey necorotex, we used recombinant
      retroviruses to label individual progenitor cells in the ventricular zone (VZ),
      then determined histochemically the distribution of their progeny during and
      after the period of cortical neurogenesis. Distribution patterns of labeled cells
      in the VZ suggested the coexistence of asymmetrically and symmetrically dividing
      progenitor cells, indicating that both postmitotic and mitotic progeny are
      produced during cortical neurogenesis. In the cortex, several distinct patterns
      of clonal distribution were observed and interpreted as follows: clones aligned
      radially suggested that asymmetrically dividing progenitors generate sequential
      "siblings" that migrate, in tandem, along a common radial path to the cortex. In
      contrast, clones oriented horizontally within a single lamina suggested that
      symmetric divisions produce multiple, laterally displaced progenitors which, in
      turn, simultaneously generate "cousin" cells that migrate, in concert, to the
      same cortical layer. Thus, we propose that different mitotic lineages, which
      coexist in the monkey VZ, produce distinct radial or laminar patterns of clone
      deployment that foreshadow the cytological organization of the adult neocortex.

PMID- 7646889
TI  - Circadian rhythms in Drosophila can be driven by period expression in a
      restricted group of central brain cells.
AB  - Neural tissues controlling circadian rhythmicity have been identified in a
      variety of organisms and are often closely associated with the visual system. In
      Drosophila, the clock gene period (per), which is required for circadian rhythms,
      is expressed in many neurons and glia throughout the eye and brain. We asked
      whether biological rhythms could be generated if per expression were restricted
      to a subset of these cells that is involved in photoreception. Here we
      demonstrate that expression of per under the control of the glass promoter
      confers both behavioral and molecular rhythmicity. glass is required for
      development of Drosophila photoreceptors, and this promoter is active in eyes,
      ocelli, and certain cells of the central brain. When we genetically removed all
      external photoreceptor cells, rhythms persisted in these transgenic animals. This
      suggests that a few central brain cells producing glass and per are capable of
      generating biological rhythms.

PMID- 7646890
TI  - Characterization of a novel protein regulated during the critical period for song
      learning in the zebra finch.
AB  - A male zebra finch learns a song by listening to a tutor, but song learning is
      normally restricted to a critical period in juvenile development. Here we
      identify an RNA whose expression in the song control circuit is altered during
      this critical period. The RNA encodes a soluble presynaptic protein that forms a
      predicted amphipathic alpha helix typical of the lipid-binding domain in
      apolipoproteins. We show this protein, which we call synelfin, to be the homolog
      of the human non-A beta component (and its precursor) recently purified from
      Alzheimer's disease amyloid. We suggest this highly conserved protein may serve a
      novel function critical to the regulation of vertebrate neural plasticity.

PMID- 7646891
TI  - Peptide inhibitors of the ICE protease family arrest programmed cell death of
      motoneurons in vivo and in vitro.
AB  - Members of the CED-3/interleukin-1 beta-converting enzyme (ICE) protease family
      have been implicated in cell death in both invertebrates and vertebrates. In this
      report, we show that peptide inhibitors of ICE arrest the programmed cell death
      of motoneurons in vitro as a result of trophic factor deprivation and in vivo
      during the period of naturally occurring cell death. In addition, interdigital
      cells that die during development are also rescued in animals treated with ICE
      inhibitors. Taken together, these results provide the first evidence that ICE or
      an ICE-like protease plays a regulatory role not only in vertebrate motoneuron
      death but also in the developmentally regulated deaths of other cells in vivo.

PMID- 7646892
TI  - Deletion of a conserved juxtamembrane sequence in Trk abolishes NGF-promoted
      neuritogenesis.
AB  - Deletion of a conserved juxtamembrane sequence (KFG) in the Trk NGF receptor
      resulted in impaired neurite outgrowth, somatic hypertrophy, and induction of c
      fos, c-jun, and TIS1 immediate-early genes. In contrast, these receptors retained
      the ability to mediate NGF-promoted survival and TIS8 and TIS11 immediate-early
      gene induction. The mutated receptor also mediated unimpaired
      autophosphorylation; SHC, PLC-gamma 1, and ERK tyrosine phosphorylation; and PI-3
      kinase and ERK activation. However, SNT protein tyrosine phosphorylation, which
      wild-type receptors mediate via a ras-independent pathway, was undetectable.
      These findings indicate that the KFG sequence is indispensable for activating a
      ras-independent NGF signaling pathway involved in promoting neuronal
      differentiation and highlight potential roles of non-tyrosine-containing receptor
      domains in growth factor signal transduction.

PMID- 7646893
TI  - Long-term depression in cerebellar Purkinje neurons results from coincidence of
      nitric oxide and depolarization-induced Ca2+ transients.
AB  - The role of nitric oxide (NO) in the induction of long-term depression (LTD) in
      the cerebellum was explored using a new, organic, membrane-impermeant form of
      caged NO. NO photolytically released inside Purkinje neurons mimicked parallel
      fiber (PF) activity in synergizing with brief postsynaptic depolarization to
      induce LTD. Such LTD required a delay of < 50 ms between the end of photolysis
      and the onset of depolarization, was prevented by intracellular Ca2+ chelation,
      and was mutually occlusive with LTD conventionally produced by PF activation plus
      depolarization. Bath application of NO synthase inhibitor or of myoglobin, a NO
      trap, prevent LTD induction via PF stimulation, but not that from intracellular
      uncaged NO, whereas intracellular myoglobin blocked both protocols. NO is
      therefore an anterograde transmitter in LTD induction. A biochemical requirement
      for simultaneous NO and elevation of intracellular free Ca2+ would explain why PF
      activity must coincide with postsynaptic action potentials.

PMID- 7646894
TI  - Evidence for silent synapses: implications for the expression of LTP.
AB  - Recent work has suggested that some proportion of excitatory synapses on
      hippocampal CA1 pyramidal cells that express NMDA receptors (NMDARs) may not
      express functional AMPA receptors (AMPARs), thus making these synapses silent at
      the resting membrane potential. In agreement with this hypothesis, we demonstrate
      here that it is possible to stimulate synapses that yield no detectable
      excitatory postsynaptic currents (EPSCs) when the cell is held at -60 mV; yet at
      positive holding potentials (+30 to +60 mV), EPSCs can be elicited that are
      completely blocked by the NMDAR antagonist, D-APV. When these functionally silent
      synapses are subjected to an LTP induction protocol, EPSCs mediated by AMPARs
      appear and remain for the duration of the experiment. This conversion of silent
      synapses to functional synapses is blocked by D-APV. These results suggest that
      LTP may involve modification of AMPARs that, prior to LTP, were either not
      present in the postsynaptic membrane or electrophysiologically silent. This
      mechanism may account for several experimental results previously attributed to
      presynaptic changes in quantal content.

PMID- 7646895
TI  - Channels underlying the slow afterhyperpolarization in hippocampal pyramidal
      neurons: neurotransmitters modulate the open probability.
AB  - The slow afterhyperpolarization in hippocampal pyramidal neurons is mediated by a
      calcium-activated potassium current (IAHP) and is a target for variety of
      different neurotransmitters. The characteristics of the channels underlying IAHP
      and how they are modulated by neurotransmitters are, however, unknown. In this
      study, we have examined the properties of the channels underlying IAHP using
      fluctuation analysis of the macroscopic current. Our results indicate that this
      channel has a unitary conductance of 2-5 pS and a mean open time of about 2 ms.
      When the peak amplitude of IAHP was maximal, these channels have an open
      probability of 0.4. Noradrenaline and carbachol reduced IAHP amplitude by
      lowering open channel probability. These result indicate that a novel calcium
      activated potassium channel underlies IAHP. This channel is modulated in a
      similar fashion by two different transmitter systems that utilize distinct
      protein kinases.

PMID- 7646896
TI  - Postsynaptic injection of CA2+/CaM induces synaptic potentiation requiring CaMKII
      and PKC activity.
AB  - CA2+-regulated protein kinases play critical roles in long-term potentiation
      (LTP). To understand the role of Ca2+/calmodulin (CaM) signaling pathways in
      synaptic transmission better, Ca2+/CaM was injected into hippocampal CA1 neurons.
      Ca2+/CaM induced significant potentiation of excitatory synaptic responses, which
      was blocked by coinjection of a CaM-binding peptide and was not induced by
      injections of Ca2+ or CaM alone. Reciprocal experiments demonstrated that
      Ca2+/CaM-induced synaptic potentiation and tetanus-induced LTP occluded one
      another. Pseudosubstrate inhibitors or high-affinity substrates of CaMKII or PKC
      blocked Ca2/CaM-induced potentiation, indicating the requirement of CaMKII and
      PKC activities in synaptic potentiation. We suggest that postsynaptic levels of
      free Ca2+/CaM is a rate limiting factor and that functional cross-talk between
      Ca2+/CaM and PKC pathways occurs during the induction of LTP.

PMID- 7646897
TI  - Inward rectification of both AMPA and kainate subtype glutamate receptors
      generated by polyamine-mediated ion channel block.
AB  - CA2+-permeable glutamate receptors assembled from subunits containing a GLN
      residue at the RNA editing site in membrane domain 2 show strong inward
      rectification. In HEK 293 cells transfected with the kainate receptor subunit
      GluR6(Q), inward rectification is lost in outside-out patches, suggesting a role
      for diffusible, cytoplasmic factors. Inclusion of different polyamines in the
      internal solution restored inward rectification, whereas Mg2+ (1 mM) was
      inactive. Spermidine (Kd[0 mV] = 5.5 microM) was of higher affinity than
      spermidine (Kd[0 mV] = 25.4 microM) or putrescine (Kd[0 mV] = 1.2 mM). AMPA
      receptors assembled from GluRA(flip) showed even higher affinity for spermine
      (Kd[0 mV] = 1.5 microM). Analysis of the voltage dependence of whole-cell
      responses predicted intracellular free spermine and spermidine concentrations of
      51 and 153 muM, respectively.

PMID- 7646898
TI  - An aspartic acid residue important for voltage-dependent gating of human muscle
      chloride channels.
AB  - A point mutation (D136G) predicting the substitution of glycine for aspartate in
      position 136 of the human muscle Cl- channel (hClC-1) causes recessive
      generalized myotonia. Heterologous expression of a recombinant D136G produces
      functional Cl- channels with profound alterations in voltage-dependent gating,
      without concomitant changes in pore properties. The mutant exhibits slowly
      activating current upon hyperpolarization, in contrast to wild-type channels,
      which display time-dependent current decay (deactivation) at negative membrane
      potentials. Steady-state activation of D136G depends upon the transmembrane Cl-
      gradient, reaching zero at voltages positive to the Cl- reversal potential in
      physiological Cl- distribution. This explains the reduced sarcolemmal Cl-
      conductance that causes myotonia. The functional disturbances exhibited by D136G
      may stem from a defect in the ClC-1 voltage sensor.

PMID- 7646899
TI  - Reversal of age-dependent cognitive impairments and cholinergic neuron atrophy by
      NGF-secreting neural progenitors grafted to the basal forebrain.
AB  - A highly NGF-secreting cell line was generated by retroviral transduction of a
      conditionally immortalized CNS-derived neural progenitor cell line. After
      transplantation to the nucleus basalis magnocellularis (NBM), the cells continue
      to express the NGF transgene for at least 10 weeks, producing sufficient NGF to
      reverse cholinergic neuron atrophy in aged rats and induce cellular hypertrophy
      in young rats. In cognitively impaired aged rats, transplants of the NGF
      secreting cells placed either in the NBM and septum or in only the NBM induced a
      near-complete reversal of the spatial learning impairment. This was accompanied
      by a normalization of the size of the cholinergic neurons in the grafted areas.
      The results demonstrate that locally increased supply of NGF to the basal
      forebrain cholinergic nuclei has a significant impact on cognitive function and
      support the usefulness of neural progenitor cells for a long-term localized
      delivery of neurotrophins to the CNS.

PMID- 7646900
TI  - Treatment of advanced colorectal cancer with 5-fluorouracil and interferon-alpha:
      an overview of clinical trials.
AB  - 5-Fluorouracil (5-FU) is the most active single agent for treatment of advanced
      colorectal cancer, although objective responses occur in only 20% of patients,
      and there seems to be no impact on overall survival. Experimental findings
      suggesting that interferon-alpha (IFN-alpha) enhances 5-FU cytotoxicity have
      stimulated an increasing number of clinical trials to evaluate the therapeutic
      potential of this combination. This article summarises the possible mechanisms of
      interaction of 5-FU and IFN-alpha, and provides an overview of the current status
      of this approach in advanced colorectal cancer. A computerised (Medline) and
      manual search were performed to identify all trials using 5-FU and IFN-alpha for
      the treatment of advanced colorectal cancer published in the English literature
      between 1960 and 1994. Information abstracted included treatment regimen, number
      of patients, pretreatment status, complete and partial remissions, remission
      duration, overall survival, and toxicity. A total of 417 patients were enrolled
      in 16 trials using different regimens of 5-FU and IFN-alpha, and double
      modulation of 5-FU with leucovorin (LV) and IFN-alpha was investigated in nine
      trials involving 332 patients. The mean overall response rate in these phase II
      trials was only 31% (range 3-76) and 35% (range 0-54), respectively. Early
      results of six prospectively randomised studies of 5-FU or 5-FU/LV +/- IFN-alpha
      also did not suggest a significant enhancement of the antitumour effectiveness
      with the addition of IFN-alpha. There is increasing evidence, however, that
      administration of IFN-alpha along with 5-FU enhances toxicity. Because of their
      modest therapeutic index, currently employed regimens of 5-FU +/- LV plus IFN
      alpha cannot be recommended for routine use at the present time. The combination
      of 5-FU plus LV represents an equally effective and less expensive alternative.
      Nevertheless, there is still hope that further attempts to elucidate the complex
      mechanisms of this potentially synergistic drug combination will allow the
      rational design of regimens with a superior therapeutic index.

PMID- 7646901
TI  - High dose recombinant tumour necrosis factor (rTNF alpha) administered by
      isolation perfusion for advanced tumours of the limbs: a model for
      biochemotherapy of cancer.

PMID- 7646902
TI  - Survival of advanced ovarian cancer patients with microscopic partial response
      after surgery and first-line chemotherapy.

PMID- 7646903
TI  - Different detection rates of HER-2/NEU overexpression in ovarian carcinoma using
      two different commercially available detection kits.

PMID- 7646904
TI  - Ifosfamide, carboplatin and etoposide for good prognosis small cell lung cancer:
      are four courses inadequate? West of Scotland Lung Cancer Group.

PMID- 7646905
TI  - Elevation of serum human chorionic gonadotrophin as the only indication for
      isolated cerebral relapse of a germ cell tumour of the testis.

PMID- 7646906
TI  - Phase II study of liposome-complexed mitoxantrone in patients with advanced
      breast cancer.

PMID- 7646907
TI  - Neopterin as a monitoring parameter for treatment with BCG in superficial bladder
      cancer.

PMID- 7646908
TI  - Soluble intercellular adhesion molecule-1 in melanoma patients treated with
      liposomes containing muramyl tripeptide.

PMID- 7646909
TI  - Nuclear DNA content of persistent tumour lacks prognostic relevance for length of
      survival in patients undergoing second-look laparotomy for ovarian cancer.

PMID- 7646910
TI  - New directions with hormone therapy in prostate cancer: possible benefit from
      blocking prolactin and use of hormone treatment intermittently in combination
      with immunotherapy.

PMID- 7646911
TI  - Prognostic factors in rectal cancer.

PMID- 7646912
TI  - The search for causes of the leukaemias.

PMID- 7646913
TI  - A case for synchronous reduction of testicular androgen, adrenal androgen and
      prolactin for the treatment of advanced carcinoma of the prostate.
AB  - The present study was undertaken mainly to investigate whether prolactin
      manipulation combined with maximal androgen blockage improves the effectiveness
      of treatment in advanced prostatic cancer. The efficacy of oral hydrocortisone as
      an alternative to commercial anti-androgens in reducing the adrenal androgens,
      and of bromocriptine in reducing the prolactin level were also examined. A
      consecutive series of 30 patients with untreated and advanced prostatic cancer
      were entered into a three-arm prospective randomised trial. 10 patients received
      subcapsular orchiectomy alone (arm 1), another 10 had subcapsular orchiectomy
      plus flutamide (arm 2), and the remaining 10 had subcapsular orchiectomy plus
      oral hydrocortisone and bromocriptine (arm 3). Clinical and biochemical
      parameters, including trans-rectal ultrasound-determined prostatic volumes,
      hormonal profiles and radionuclide bone scan were evaluated at regular intervals.
      At 12 months, serum testosterone was reduced by more than 90% in all arms,
      however, maximum suppression of androstenedione, prolactin, and reduction of
      prostatic volumes were only observed in arm 3; this was reflected by the
      significant improvement in clinical response in arm 3 compared with other arms.
      This study suggests that a combined maximal suppression of androgens and
      prolactin offers a significant improvement in response over conventional
      treatments without prolactin suppression in the treatment of advanced prostatic
      cancer. Importantly, a better clinical outcome in arm 3 was still apparent at the
      end of 36 months.

PMID- 7646914
TI  - Chemoimmunotherapy of advanced malignant melanoma: sequential administration of
      subcutaneous interleukin-2 and interferon-alpha after intravenous dacarbazine and
      carboplatin or intravenous dacarbazine, cisplatin, carmustine and tamoxifen.
AB  - Both chemotherapy and interleukin-2 and/or interferon-alpha produce objective
      responses in a proportion of advanced malignant melanoma patients. While duration
      of response to chemotherapy is short, i.e. usually below 4 months, immunotherapy
      has resulted in a small number of long-lasting remissions in patients with
      metastatic melanoma. In two consecutive phase II trials in a total of 67
      patients, we assessed the potential synergism between both modalities, i.e. chemo
      and immunotherapy. Treatment consisted of intravenous (i.v.) carboplatin (CBDCA,
      400 mg/m2) and dacarbazine (DTIC, 750 mg/m2) given twice (i.v. bolus over 30 min)
      at 3-week intervals, or 4 cycles of DTIC (220 mg/m2 i.v. 3 days), cisplatin (DDP,
      35 mg/m2 i.v. 3 days), carmustine (BCNU, 150 mg/m2 i.v. cycles 1 and 3) and
      tamoxifen (TAM, 20 mg oral/daily) at 3-week intervals. Chemotherapy was followed
      by immunotherapy with combined subcutaneous (s.c.) interleukin-2 (rIL-2) and SC
      interferon-alpha 2 (rIFN-alpha). Among 40 patients who received a full cycle of
      chemotherapy with CBDCA/DTIC and sequential immunotherapy, there were 3 (7.5%)
      complete remissions (CRs) with a median duration of 19 months (range 13-26+).
      Partial remissions (PRs) were noted in 11 (27.5%) patients with a median response
      duration of 8 (range 5-14) months. Among 27 patients who received
      DTIC/DDP/BCNU/TAM and rIL-2/rIFN-alpha, there were 3 (11%) complete remissions
      and 12 (44.5%) partial remissions. Duration of complete and partial remissions
      ranged from 9+ to 13+ (median, 11+), and 5 to 15+ (median, 7+) months,
      respectively. Chemotherapy produced mostly moderate toxicity. Thrombocytopenia
      was common with the nadir after a median time of 18 days following start of
      CBDCA/DTIC and DTIC/DDP/BCNU, respectively. 10 patients required transfusion of
      thrombocytes. Nausea and vomiting due to chemotherapy were well tolerated using
      concomitant ondansetrone (8 mg i.v.). Immunotherapy was self-administered at home
      with mild to moderate side effects; malaise, fever, chills, nausea/vomiting,
      diarrhoea, anorexia and arthralgias were most frequent, but were spontaneously
      reversible after ending rIL-2/IFN-alpha. A mean 87 and 88% of the projected doses
      of rIL-2 and rIFN-alpha were administered on either protocol. There were no life
      threatening complications and no treatment-related deaths. The sequential
      combination of chemotherapy and rIL-2 plus rIFN-alpha had at least additive
      therapeutic activity against metastatic malignant melanoma. The schedules
      produced long-lasting remissions and were tolerated well overall. These trials
      substantiate a potential role for low to intermediate dose immunotherapy in
      maintaining and consolidating therapeutic effects of chemotherapy in metastatic
      melanoma.

PMID- 7646915
TI  - No standard treatment is available for advanced pancreatic cancer.
AB  - All randomised trials, published from 1980 to 1993, of treatments in advanced and
      locally unresectable exocrine pancreatic carcinoma were critically reviewed to
      identify the most effective therapeutic strategy for use as a control arm in
      randomised trials for such patients. All the published randomised trials on
      patients with pancreatic cancer were identified, and the treatment results
      summarised by means of published methodological guidelines. Twenty-seven reports,
      including 21 on hormonal or chemotherapy and six on radio/chemotherapy were
      identified. Very different treatment programmes were used in the trials, without
      a rationale sequence for testing hypotheses. Furthermore, several methodological
      drawbacks undermined both the internal and the external validity of these
      studies. Therefore, no meta-analysis can be conducted, combining the results of
      the randomised controlled trials in pancreatic cancer published from 1990 to
      1993; no standard treatment is currently available for patients with advanced
      pancreatic cancer; future studies should screen new drugs or new combinations;
      and an untreated control group should be included in future comparative studies
      until real advantages in terms of better quality of life or improved survival are
      demonstrated.

PMID- 7646916
TI  - Plasma tetranectin and colorectal cancer.
AB  - The prognostic significance of plasma tetranectin (PL-TN) in colorectal cancer
      was retrospectively examined in 504 patients (80 Dukes' A, 174 Dukes' B, 98
      Dukes' C and 152 Dukes' D). Follow-up time was 7-12 years. No significant
      prognostic variable was found for Dukes' A patients by Cox multivariate analysis.
      In stage B, PL-TN was the second strongest prognostic variable [relative hazard
      (RH) = 3.3 for patients with PL-TN < or = 7.5 mg/l]. The other prognostic
      variables were perineural invasion (RH = 3.7), tumour distance < or = 10 cm from
      the anal verge (RH = 3.0), postoperative radiotherapy (RH = 2.9) and a high
      carcinoembryonic antigen (CEA) score (RH = 1.8). In Dukes' C, only CEA score and
      gender were of prognostic significance. For Dukes' D, PL-TN was the only
      prognostic variable (RH = 1.7). Testing all patients in one multivariate
      analysis, Dukes' staging was the strongest and PL-TN the second strongest
      prognostic variable. The shortened survival for patients with low PL-TN levels is
      illustrated with lifetables.

PMID- 7646917
TI  - Prognostic value of neural invasion in rectal carcinoma: a multivariate analysis
      on 339 patients with curative resection.
AB  - To determine whether neural invasion or other clinico-pathological factors are
      prognostic, we performed a retrospective study on 339 rectal carcinomas. The
      overall 5-year survival was 62%. In the multivariate analysis, age over 60 years,
      a distance from the anal verge of less than 6 cm, the number of positive lymph
      nodes, neural invasion and tumour penetration were found to be prognostic. A
      scoring system identified five prognostic groups of patients. Neural invasion is
      an independent prognostic factor in our scoring system and it is suggested that
      this parameter should be taken into consideration for postsurgical treatment.

PMID- 7646918
TI  - Tumour marker CA15-3: possible uses in the routine management of breast cancer.
AB  - Tumour markers are a potentially powerful means of obtaining information about
      cancers whilst causing minimal morbidity, inconvenience and cost. CA15-3 has been
      suggested as a marker of distant metastasis (M+ disease) in breast cancer. We
      have measured CA15-3 in 77 patients with carcinoma of the breast in order to
      determine whether routine assay of this tumour marker would be useful in the
      oncology unit of a district general hospital. A highly significant correlation
      existed between elevated CA15-3 levels (> or = 30 U/ml) and M+ disease. The CA15
      3 assay was found to have a sensitivity of 70%, a specificity of 96% and a
      predictive value of 87%, in agreement with previous studies. There was evidence
      that CA15-3 levels frequently increased in advance of otherwise detectable
      distant metastases. 70 patients had a 99m Tc bone scan close to the date on which
      CA15-3 was measured. All patients with a positive bone scan and raised levels of
      CA15-3 were subsequently confirmed as having bony metastases; no patient with
      normal bone scan and normal CA15-3 developed M+ disease (to the date of follow
      up). CA15-3 levels were raised in 83% of patients who developed non-bony distant
      metastases. In clinical practice it may be possible to exploit the high
      specificity of CA15-3, in order to provide additional information to that already
      determined by current investigations. For example, CA15-3 might be assayed
      alongside a bone scan to confirm positive or negative results. Another role might
      be as a screen for breast cancer metastases in departments with limited access to
      bone scans and other imaging facilities. CA15-3 might also be used in monitoring
      patients for the development of distant metastases during follow-up. It is,
      however, unlikely that CA15-3 can substitute directly for a bone scan or other
      imaging currently used routinely by a department. Clinical trials are now
      necessary to determine the effect of using tumour markers such as CA15-3 on
      patient morbidity and mortality.

PMID- 7646919
TI  - Long-term results of a multicentre randomised, comparative phase III trial of
      CHOP versus CNOP regimens in patients with intermediate- and high-grade non
      Hodgkin's lymphomas. Novantrone International Study Group.
AB  - 59 previously untreated patients with intermediate- or high-grade, stage II-IV
      non-Hodgkin's lymphoma (NHL) were entered into an open-label, randomised,
      multicentre study to compare the efficacy and safety of CHOP (cyclophosphamide,
      doxorubicin, vincristine and prednisolone) with that of CNOP (cyclophosphamide,
      mitoxantrone, vincristine and prednisolone). 10 patients refused treatment
      following randomisation. The remaining 349 patients received either the CHOP or
      CNOP regimen every 3 weeks for a maximum of six to eight cycles. The
      randomisation procedure was violated for 34 patients treated at two study
      centres. Data from these 34 patients were analysed separately for efficacy and
      survival. Data from the remaining 325 patients, 164 assigned to CHOP and 161 to
      CNOP, were used in the major efficacy and survival analyses. Of these 325
      patients, 263 (81%) met the eligibility criteria of the protocol. Supplementary
      analyses of data from these 263 patients, 132 assigned to CHOP and 131 to CNOP,
      were conducted for efficacy and survival. Data from all 349 treated patients were
      analysed for safety. In the 325 randomised patients, the overall objective
      response rate was not significantly different between the two groups (chi 2 test,
      P = 0.35). The CHOP regimen had a 51% (83/164) complete remission (CR) rate
      compared with 40% (64/161) for the CNOP regimen (P = 0.05). Among those with CR,
      the median time to response was 104 days with the CHOP regimen and 77 days with
      the CNOP regimen, and the median duration of CR was 667 and 1833 days,
      respectively. The median time to progression was 449 days for CHOP patients and
      564 days for CNOP patients. The median survival time was 932 days for CHOP
      patients and 1801 days for CNOP patients, with a risk of death on CNOP relative
      to CHOP of 0.93% (95% confidence interval 0.68-1.27). After 5 years, 50% of
      patients in the CNOP arm and 40% of patients in the CHOP arm were still alive;
      these differences between treatment groups were not statistically significant.
      The median time to treatment failure (TTF) was 285 days for patients on the CHOP
      arm and 282 days for patients on the CNOP arm. Separate analyses of 263 eligible
      randomised patients, and 34 patients in whom the randomisation procedure was not
      followed, yielded similar results for remission rate, TTF, duration of CR and
      estimated overall survival. The incidence of non-haematological events, such as
      severe nausea and vomiting (P < 0.01), mucositis (P < 0.05) and alopecia (P <
      0.001), were significantly lower in were significantly lower in patients treated
      with CNOP as compared with those who received the CHOP regimen. The incidence of
      cardiovascular toxicity of any severity was similar in the two groups. While
      severe and potentially life-threatening neutropenia occurred more frequently in
      patients treated with CNOP compared with CHOP (0.05 > P > 0.10), the incidence of
      infection of any severity was similar in both arms. We conclude that CHOP and
      CNOP regimens were both efficacious in patients with previously untreated
      aggressive NHL.

PMID- 7646920
TI  - Heterogeneity of intratumour proliferative activity in primary breast cancer:
      biological and clinical aspects.
AB  - The present retrospective study was undertaken to verify whether the extent of
      intratumour proliferative activity variation or the method of quantifying tumour
      proliferative activity is related to biological characteristics and clinical
      outcome in a series of operable node-negative breast cancer patients. For tumour
      proliferative activity evaluation, the 3H-thymidine autoradiographic assay was
      used. After incubation of 3-8 samples from different areas of the equatorial
      section of each tumour for 1 h at 37 degrees C with 3H-thymidine, the following
      methods were used for evaluation of tumour cell labelling: mean tumour labelling
      index (LI), the highest labelling value from a specific area (LI-max), and the
      extent of intratumour labelling variation from several samples (LI-CV). LI-max
      was related to ER and PgR status, and linearly correlated with LI (c.c. = 0.92, P
      < 10(-6)) whereas LI-CV was independent of tumour size, grade ER and PgR status,
      but dependent on the number of tumour samples analysed for each tumour. After 5
      years of median follow-up, disease-free survival was only related to tumour size
      (T1 versus T2: 84 versus 64%, P < 0.04 by log rank analysis) and different LI
      values (low versus high 3H-Tdr-LI:86 versus 61%, P < 0.03 by log rank analysis).
      LI-max and LI-CV values were not significantly related to clinical outcome. Cox
      multivariate analysis confirmed the independent prognostic value of LI and tumour
      size on disease-free survival.

PMID- 7646921
TI  - Fluorescence polarisation changes in lymphocyte cytoplasm as a diagnostic test
      for breast carcinoma.
AB  - Lymphocytic cytoplasm from individuals with malignant disease, and from those
      without, differ in such a way as to be diagnostic both of malignancy generally
      and of specific types of cancer. Mitogenic stimulation of lymphocytes by
      phytohaemagglutinin (PHA) and antigenic stimulation by encephalitogenic factor
      (EF) and certain specific tumour-associated antigens, provokes changes in the
      structure of the cytoplasmic matrix (SCM) which are detectable upon fluorescence
      polarisation. The degree of change is quantifiable both by calculating the
      polarisation ration (PR, polarisation before and after stimulation) and the
      relative ratio (RRSCM, the ratio between the polarisation obtained after exposure
      to EF [PEF] and to the polarisation measured after exposure to PHA [PPHA]). A new
      tumour-associated antigen specific for breast cancer, CaBr, was tested for its
      diagnostic efficacy in comparison with that of EF, by prospectively testing blood
      samples from 138 consecutive women with suspicious breast masses. The previously
      known discriminatory power (sensitivity 60.7% and specificity 90.7%) of the
      polarisation-derived RRSCM was reconfirmed. However, the RR'SCM (the new ratio
      using CaBr instead of EF), was significantly more sensitive (77.4%; P < 0.01) and
      specific (94.4%) than the RRSCM in detecting breast cancers. The polarisation
      changes in the cytoplasmic matrix after stimulation by CaBr alone suggest the
      best discriminatory power (sensitivity 90.5% and specificity 94.4%) between
      cancerous and non-cancerous patients.

PMID- 7646922
TI  - Antioxidant-related parameters in patients treated for cancer chemoprevention
      with N-acetylcysteine.
AB  - N-acetylcysteine (NAC) is an antioxidant, possibly effective in the early steps
      of carcinogenesis, and is applied to prevent second primary tumours in the upper
      aerodigestive tract and the lungs. In this study, we evaluated the
      pharmacodynamic profile of 600 mg NAC treatment, given daily for 3 months.
      Treatment caused a significant increase of the non-protein-SH concentration in
      blood plasma (38%) and erythrocytes (31%). Glutathione levels in exfoliated
      buccal mucosa cells appeared not to be influenced by treatment. The total radical
      trapping ability parameter (TRAP) of blood plasma showed no change. In vitro, the
      addition of glutathione, but not of NAC did increase the TRAP value. In addition,
      when peroxyl radicals were generated in vitro, NAC was shown to be consumed more
      rapidly than glutathione. This suggests that NAC prevents early damage, while
      glutathione functions over a longer time period.

PMID- 7646923
TI  - Clinical significance of serum S100 in metastatic malignant melanoma.
AB  - The clinical significance of serum S100 was assessed in comparison to neuron
      specific enolase (NSE) in 126 patients with malignant melanoma: 80 patients with
      clinical stage I/II, 23 patients with stage III and 23 patients with stage IV
      according to the criteria of the American Joint Committee on Cancer (AJCC). Using
      cut-off values of 0.15 micrograms/l for S100 and 12.5 micrograms/l for NSE, the
      sensitivity was found to be 1.3% (1/80) for S100 and 8.75% (7/80) for NSE in
      patients with stage I/II, 8.7% (2/23) for S100 and 13% (8/23) for NSE in patients
      with stage III, and 73.9% (17/23) for S100 and 34.8% (8/23) for NSE in patients
      with stage IV disease (P < 0.05). In 6 patients with stage III/IV tumours, serial
      measurement of serum S100 and NSE was performed. A rise of serum S100 indicated
      progression of the disease; a decline indicated response to treatment. Our
      preliminary results support the value of serum S100 as an adjunct to the clinical
      staging and monitoring of metastatic malignant melanoma.

PMID- 7646924
TI  - The influence of age on resection rates and postoperative mortality in 2773
      patients with gastric cancer.
AB  - Resection rates and postoperative mortality rates were studied in patients with
      gastric cancer, diagnosed from 1982 until 1992 in the southwestern area of the
      Netherlands. Overall, 51% of the patients underwent resection. For patients aged
      0-59, 60-69, 70-79 and 80 years and over, resection rates were 64, 55, 54 and
      35%, respectively. Tumours located in the cardia were less often resected than
      tumours of the antrum, 39 versus 71%. The postoperative mortality after
      resectional operations was 8.3%; 9.2% for men and 6.7% for women. The operative
      risk increased markedly after the age of 70 years; for patients under 70 years of
      age, the rate was 3.4% compared with 12.4% for those aged 70 years and older.
      These results indicate that elderly patients can be operated on at an acceptable
      risk, and that palliative resections may be considered, especially in patients
      younger than 70 years.

PMID- 7646925
TI  - Single-view screening mammography: psychological, endocrine and immunological
      effects of recalling for a complete three-view examination.
AB  - To investigate influences of a recall due to inconclusive findings on screening
      mammography, 45 women were examined with psychological ('mood' and 'coping'),
      endocrine and immunological tests immediately after complete mammography (first
      interview), 2-3 days after the initial screening mammography, and 3 weeks after
      the women had been informed of normal findings (second interview). The mood score
      in the first interview was significantly lower than in the second. No differences
      were found in the endocrine and immunological tests. The recall for complete
      mammography provoked a significant short-term emotional reaction not reflected in
      changes in the endocrine and immune functions.

PMID- 7646926
TI  - Determination of urinary 8-hydroxydeoxyguanosine by automated coupled-column high
      performance liquid chromatography: a powerful technique for assaying in vivo
      oxidative DNA damage in cancer patients.
AB  - An automated analytical method has been developed for determination of the
      oxidative DNA adduct, 8-hydroxydeoxyguanosine (8OHdG) in human urine, based on
      coupled-column high performance liquid chromatography with electrochemical
      detection. Urine is concentrated on Bondelut CH by means of an automated sample
      processor, and the enriched sample injected on to a polymeric reversed phase
      column coupled in line with an electrochemical detector and a C18 reversed phase
      column. By use of the electrochemical detector, a suitable retention time
      interval is set for collection of the fraction containing 8OHdG from the
      chromatography on the first column; this fraction is collected in a 2 mL loop and
      injected onto the C18 column. The system is operated by an automatic valve
      station controlled by an integrator. The method has a large sample capacity and
      measures 31.1, 15.7, and 7.43 nmol 8OHdG/L urine with variation coefficients of
      8, 8 and 24% within series and 8, 11 and 23% between series. Normal healthy
      individuals were found to excrete 14.9 +/- 7.8 nmol 8OHdG/24 h, or 1.11 +/- 0.62
      mumol 8OHdG per mol creatinine, in their urine, whereas increased levels of 8OHdG
      were found in 24 h collections from a variety of cancer patients, both in samples
      taken before onset of oncological therapy (1.84 +/- 1.12 mumol/mol creatinine, P
      < 0.01 versus healthy individuals) and after therapy onset (2.18 +/- 1.44
      mumol/mol creatinine, P < 0.001 versus healthy individuals). Moreover, mean
      values of 8OHdG in random urinary samples from cancer patients were significantly
      higher than from healthy individuals (2.42 +/- 2.28 versus 1.19 +/- 0.48
      mumol/mol creatinine, P < 0.001), both in samples taken before therapy onset
      (1.91 +/- 0.96, P < 0.001 versus healthy individuals) and after (2.57 +/- 2.46, P
      < 0.001 versus healthy individuals). High levels of urinary 8OHdG were found in
      patients subjected to whole body irradiation, and in patients receiving
      chemotherapy with various cytostatic agents. The potential use of the method for
      detecting increased urinary 8OHdG excretion and conditions associated with
      increased oxidative DNA damage in humans is discussed.

PMID- 7646927
TI  - Patterns of occurrence of the leukaemias.
AB  - Despite a proliferation of epidemiological studies during the past two decades,
      aetiologies of the leukaemias remain poorly understood, and characterisation of
      descriptive patterns has been limited. Recent publications of international
      mortality and incidence data, along with the expanding U.S. database, make a
      comprehensive assessment of leukaemia patterns particularly timely. Total
      leukaemia mortality has dramatically declined among children and increased among
      the elderly, while incidence has declined somewhat (for Caucasian and African
      American females) or remained stable (for African-American males) during the past
      two decades in the United States. Population-based 5-year relative survival for
      total leukaemia has risen substantially among children since the mid-1970s, and
      improved slightly among other age groups in the U.S., where survival is
      consistently higher among Caucasians than African-Americans, but differs little
      by gender. In a detailed assessment by leukaemia subtype, some important
      differences in geographic, racial/ethnic, age and trend patterns are identified,
      suggesting that the subtypes may have different aetiologic factors. Proven and
      suspected risk factors cannot explain more than a small fraction of the observed
      geographic and temporal variation in incidence. Several noteworthy subtype
      specific characteristics or trends warrant further investigation: for acute
      lymphoid leukaemia (ALL), increasing incidence, with higher rates in Spanish and
      Latino populations; for chronic lymphoid leukaemia (CLL), declining incidence,
      with dramatically low rates among Asians; for acute myeloid leukaemia (AML),
      increasing incidence among African-American males; and for chronic myeloid
      leukaemia (CML), declining rates among Caucasian but not among African-Americans.

PMID- 7646928
TI  - Striking changes in smoking behaviour and lung cancer incidence by histological
      type in south-east Netherlands, 1960-1991.
AB  - Changes in lung cancer incidence in south-east Netherlands between 1960 and 1991
      were analysed, using data from the Eindhoven Cancer Registry, and related to
      previous changes in smoking habits. Male lung cancer incidence rates increased
      markedly from birth cohorts 1890-1899 to 1910-1919, followed by a decline. The
      peak incidences for both squamous cell carcinoma and small cell carcinoma were
      reached in 1978, while for adenocarcinoma it was 1985. A rising trend in female
      lung cancer incidence up to 1988 was found for each successive birth cohort and
      for every histological type. These changes in lung cancer incidence rates are
      most likely related to the pattern of past smoking habits: the percentage of male
      adult smokers in the southern part of the Netherlands decreased from 95% in 1960
      to 40% in 1981 and the percentage of female adult smokers increased from 27% in
      1960 to 40% in 1967, slightly decreasing only after 1979. In view of the trends
      in smoking behaviour, the incidence rates for male lung cancer will decline
      further, whereas female lung cancer incidence may decrease after the year 2000.

PMID- 7646929
TI  - Effects of norcantharidin, a protein phosphatase type-2A inhibitor, on the growth
      of normal and malignant haemopoietic cells.
AB  - Cantharidin is a natural toxin that inhibits protein phosphatase type 2A (PP2A)
      and has antitumour effects in man. We have studied the synthetic analogue,
      norcantharidin (NCTD), which has less nephrotoxic and phlogogenic side-effects,
      investigating the effects on the normal haemopoietic system and leukaemia cell
      growth. Daily intraperitoneal (i.p.) injection of NCTD induced dose and circadian
      time-dependent transient leucocytosis in normal mice, but did not accelerate bone
      marrow (BM) regeneration, or have haemopoietic offe-effects following chronic
      administration. NCTD stimulated the cell cycle progression of granulocyte
      macrophage colony-forming cells (GM-CFC), stimulated DNA synthesis and increased
      the frequency of mitotic cells in short-term human BM cultures. NCTD also
      stimulated the production of interleukin (IL)-1 beta, colony stimulating activity
      (CSA) and tumour necrosis factor (TNF)-alpha. Continuous in vitro NCTD treatment,
      however, inhibited both DNA synthesis and GM-CFC growth. Fluorescence-activated
      cell sorting (FACS) analysis of DNA profiles and cytological studies in HL-60, K
      562 or MRC5V2 (fibroblast) cells indicated that low doses of NCTD accelerated the
      G1/S phase transition, while higher doses or prolonged incubations inhibited the
      cell cycle at the G2/M phases or during the formation of postmitotic daughter
      cells. Electron microscopy revealed that NCTD impaired the neogenesis of
      chromatin material and nuclear membrane during the M/G1 phase transition in K-562
      cells. The biphasic effect of NCTD may be due to inhibition of PP2A activity,
      which regulates the cell cycle, both at the restriction point and at the G2 and M
      phases. Our data provide new insight into the cellular and molecular actions of
      NCTD, and partly explain its therapeutical effects in cancer patients.

PMID- 7646930
TI  - Growth inhibition by 8-chloro cyclic AMP of human HT29 colorectal and ZR-75-1
      breast carcinoma xenografts is associated with selective modulation of protein
      kinase A isoenzymes.
AB  - Significant dose-related inhibition of growth of HT29 human colorectal cancer
      xenografts and ZR-75-1 breast cancer xenografts in immune-suppressed mice was
      induced by the cyclic AMP analogue, 8-chloroadenosine 3',5'-cyclic monophosphate
      (8-Cl-cyclic AMP) when given by alzet mini-pumps over a 7-day period at doses of
      either 50 or 100 mg/kg/day. Levels and types of cyclic AMP binding proteins were
      measured by ligand binding and photoaffinity labelling, respectively, in tumours
      harvested at the end of the treatment period. Compared with levels in tumours
      from control animals, values of tumour cyclic AMP binding proteins from treated
      animals were significantly reduced. These effects were associated with an
      apparent modulation of the types of cyclic AMP binding proteins, 8-Cl-cyclic AMP
      treated xenografts displaying a reduced ratio of RI/RII isoforms compared with
      untreated control tumours.

PMID- 7646932
TI  - Influence of indomethacin and difluoromethylornithine on human tumour growth in
      nude mice.
AB  - Biopsy material from six human colorectal carcinomas was transplanted to 114 nude
      mice. A treatment protocol was established which included no treatment (control,
      C), indomethacin (I), difluoromethylornithine (D) or a combination of both (ID).
      The influence of the various drugs on tumour weight and protein kinase CK2
      activity was monitored. CK2 activity was measured because in all tumours examined
      so far the enzyme activity was found to be enhanced several-fold when compared to
      the non-neoplastic tissue of the same patient. More than half of the investigated
      tumours showed a conspicuous reduction in weight after drug treatment, and I and
      the combination of D/I were significantly effective using the mixed model
      analysis. Furthermore, we have tried to discover whether there is a change in the
      subcellular localisation of protein kinase CK2 subunits associated with drug
      treatment. We analysed the tumours and the non-neoplastic control tissues by
      immunohistochemistry using antibodies directed against the CK2 subunits and
      against the proliferation marker Mib. In addition, we have also investigated the
      behaviour of the nucleolar protein B23 which has also been shown to be enhanced
      several-fold in rapidly proliferating tissue and which is also a substrate for
      CK2. The immunohistochemical data suggest that, irrespective of the drug
      treatment and the observed reduction in CK2 activity, the CK2 subunits remain
      localised in the nucleus.

PMID- 7646931
TI  - Modulation of the antitumour activity of cisplatin alone and in combination with
      5-fluoro-2'-deoxyuridine by N-phosphonacetyl-L-aspartate in murine colon
      carcinoma no. 26.
AB  - Modulation of the therapeutic efficacy of cisplatin (CDDP) and 5-fluoro-2'
      deoxyuridine (FdUrd) alone and in combination with N-phosphonacetyl-L-aspartate
      (PALA) was evaluated in mice bearing colon carcinoma (C-26) using a weekly
      intravenous (i.v.) push schedule for 3 weeks. A non-toxic dose of PALA (100
      mg/kg) was administered i.v. 24 h prior to the i.v. administration of CDDP +/-
      FdUrd. The maximum tolerated doses (MTD) of CDDP and FdUrd when used as a single
      agent were 9 and 400 mg/kg, respectively. In combination, however, the MTD of
      CDDP and FdUrd were 2.5 and 300 mg/kg, respectively. PALA did not significantly
      affect the MTD. PALA improved the antitumour activity of CDDP or FdUrd when used
      alone; however, the highest tumour response, 66% complete tumour regression, was
      achieved with a PALA modulation of CDDP and FdUrd in combination.

PMID- 7646933
TI  - Relationships between resistance to cisplatin and antifolates in sensitive and
      resistant tumour cell lines.
AB  - Possible relationships between tumour resistance to cisplatin and the folate
      based thymidylate synthase (TS) inhibitors, CB3717 and ZD1694 (tomudex), have
      been investigated in vitro using a panel of tumour cell lines (predominantly
      human ovarian), either parental or possessing acquired resistance to cisplatin or
      ZD1694. Across eight parent human tumour cell lines, ZD1694 was the most potent
      drug (mean IC50 of 1.9 x 10(-8) M), being over 250 times as potent as its
      prototype CB3717 (mean IC50 of 4.8 x 10(-6) M). In five pairs of acquired
      cisplatin-resistant human tumour cell lines (three ovarian, one cervical and one
      testicular) which encompass all of the main known mechanisms of platinum drug
      resistance, ZD1694, CB3717 and the DHFR inhibitor, methotrexate, all exhibited
      non-cross-resistance. The cervical line, HX/155cisR, showed collateral
      sensitivity to ZD1694, CB3717, 5-fluorouracil (FUra) and fluorodeoxyuridine
      (FdUrd). One cell line, A2780cisR, showed a low level of cross-resistance to FUra
      (resistance factor, RF, of 1.5) and FdUrd (RF of 3.8). A2780cisR, in common with
      two other cisplatin-resistant lines, did not possess elevated TS activity
      compared with its parent. Cisplatin retained activity in four acquired ZD1694
      resistant cell lines (encompassing reduced folate transport, elevated TS and
      defective polyglutamation mechanisms of resistance). Furthermore, combinations of
      ZD1694 with each of the platinum-based drugs, cisplatin, carboplatin and the
      recently introduced orally administrable, JM216, all showed additive growth
      inhibitory effects by median effect analysis. These data suggest that the tumour
      inhibitory properties of the recently introduced highly potent TS inhibitor,
      ZD1694, and cisplatin, and, moreover, their respective mechanisms of resistance,
      do not overlap. Therefore, these drugs may be considered for combination in the
      clinic.

PMID- 7646934
TI  - Late renal damage after total body irradiation and bone marrow transplantation in
      a mouse model: effect of radiation fractionation.
AB  - In response to the accumulating evidence that renal damage is now becoming an
      important late complication after total body irradiation (TBI) and bone marrow
      transplantation (BMT), we have tested the effect of fractionated and
      hyperfractionated TBI on late kidney damage in a mouse model. TBI was given as
      fractionated (three fractions in 3 days, Fx 3), or hyperfractionated (nine
      fractions in 3 days, Fx 9) treatment. Kidney damage was evaluated using
      [51Cr]EDTA residual activity, blood urea nitrogen (BUN) and percentage
      haematocrit (%Hct) as end-points. We were able to detect progressive renal damage
      with no evidence of recovery or plateau in the Fx 3 and Fx 9 schedules. The time
      latency before the expression of renal damage was dependent on both total dose
      and end-point and it was shorter the higher the dose. [51Cr]EDTA detected renal
      damage at the same doses as BUN but earlier in time whereas %Hct detected renal
      damage at doses lower than both BUN and [51Cr]EDTA. Reducing the dose per
      fraction spared the kidney from TBI damage. The dose-response curves for renal
      damage (using the [51Cr]EDTA end-point) were steep, and tended to shift towards
      lower doses with longer follow-up times. The dose-modifying factors defined as
      the dose needed to cause renal damage in 50% of the animals (ED50) using single
      fraction TBI divided by the ED50 using fractionated TBI were 1.3 and 1.9 for the
      Fx 3 and Fx 9, respectively. These results may indicate that patients treated
      with TBI and BMT should be assessed for late kidney damage and that fractionation
      and particularly hyperfractionation may protect the kidneys from TBI-induced
      renal damage.

PMID- 7646936
TI  - Metachronous pulmonary metastases resection in patients with Ewing's sarcoma
      initially treated with adjuvant or neoadjuvant chemotherapy.
AB  - 55 patients with Ewing's sarcoma of bone, treated at our Institution with
      adjuvant or neoadjuvant chemotherapy between 1972 and 1990, relapsed with
      pulmonary metastases alone. 12 of these patients--selected according to their
      long disease-free interval before relapse, monolaterality of the lesions, small
      numbers of metastatic nodules, resectability and refusal to undergo further
      chemotherapic treatments--were treated with surgical resection of the metastatic
      lesions and with no additional radio- or chemotherapy. At a follow-up ranging
      between 3 and 14 years (mean 9 years), 5 of these 12 patients (42%), were
      continuously free of disease, whereas the remaining 7 patients died with
      uncontrolled disease 12-39 months (mean 22 months) after thoracotomy. These
      results seem to indicate that an aggressive surgical approach should be
      considered for a selected group of Ewing's sarcoma patients who relapse with only
      lung metastases.

PMID- 7646935
TI  - Childhood malignancies in Germany--methods and results of a nationwide registry.
AB  - Since 1980, a nationwide registry of childhood malignancies has been established
      in the Federal Republic of Germany. The registry combines features of a
      population-based and a hospital-based registry. Basic registry data are
      complemented and validated by data from all ongoing clinical trials in paediatric
      oncology. Descriptive analyses are presented for the first 13 years of operation
      of the registry. In addition, time trends and regional variations of incidence
      within the Federal Republic of Germany are shown. A brief description of
      completed and ongoing registry-based epidemiological studies is given.

PMID- 7646937
TI  - President's message: member feedback will guide phototherapy certification and
      associate member issues.

PMID- 7646938
TI  - Skin cancer--the need for continuing education.

PMID- 7646939
TI  - Neuropathic wounds.
AB  - Neuropathic wounds commonly seen in the diabetic patient are particularly
      challenging diagnostic and management entities. An overview of this disorder
      along with clinical manifestations and treatment options are discussed.

PMID- 7646940
TI  - Phototoxicity and photoallergy.
AB  - Phototoxic and photoallergic reactions resulting from a combined exposure to
      photosensitizing chemicals and light are common. Diagnosis of such reactions
      requires an understanding of its clinical presentation and recognition of
      commonly encountered photosensitizers. Phototesting allows identification of the
      photosensitizer and appropriate management of the patient.

PMID- 7646941
TI  - What's your assessment? Urticaria.

PMID- 7646942
TI  - Zingiber officinale (ginger) used to prevent 8-Mop associated nausea.
AB  - Patients undergoing photopheresis are required to ingest the drug 8-MOP as part
      of their treatment. This drug causes nausea as a side effect. Ginger taken prior
      to 8-MOP may substantially reduce this side effect. This study compared patients'
      nausea when taking 8-MOP with and without ginger.

PMID- 7646943
TI  - Sunscreens.
AB  - Dermatology nurses can advise patients about sunscreen use and sun exposure. A
      patient's sun-protection plan may include both traditional sunscreens and daily
      use products. Understanding terms such as sun-protection factor and ultraviolet A
      protection facilitates patient communication.

PMID- 7646944
TI  - Effects of a community outreach program in HIV risk behaviors among injection
      drug users in San Juan, Puerto Rico: an analysis of trends.
AB  - This report assesses the effects of a community outreach program in reducing HIV
      risk behaviors among injection drug users (IDUs) in San Juan, Puerto Rico.
      Participants were 1,113 IDUs, 88.3% of whom were also assessed at post
      intervention. The analytic strategy consisted in modeling pre- and post
      intervention trends in risk behavior levels from successive cohorts of IDUs. The
      trend analyses showed that secular trends, unrelated to the direct effects of the
      outreach intervention, accounted for significant portions of the reported risk
      reductions. Nevertheless, the post-intervention trends in the shared use of
      cookers and in needle bleaching showed shifts that could not be accounted for by
      the modeled secular trends. The outreach intervention appears to have had
      significant but partial effects on the behavioral risks associated to drug
      injection and no effect on sexual behaviors. The strengths and weaknesses of time
      trend analyses for evaluating community HIV-prevention programs lacking
      experimental designs are discussed.

PMID- 7646946
TI  - The effect of a single affective HIV/AIDS educational program on college
      students' knowledge and attitudes.
AB  - The number of AIDS cases, since its identification by the Centers for Disease
      Control (CDC) in 1981, has continued to escalate at a very alarming rate. A
      population at increased risk of acquiring AIDS is college students, because of
      their behavior, especially personal and sexual exploration (D'Augelli & Kennedy,
      1989; American College Health Association, 1988; Hirschorn, 1987).

PMID- 7646945
TI  - Interim outcomes for a community-based program to prevent perinatal HIV
      transmission.
AB  - The AIDS Prevention for Pediatric Life Enrichment (APPLE) project is a community
      based program to prevent perinatal HIV infection by preventing infection in
      women. One project component tested a primary prevention model developed from
      principles of cognitive social learning theory which used street outreach and
      community-targeted small media materials to increase the use of condoms.
      Formative research was used to explore community perceptions about HIV/AIDS and
      to design media materials. Program evaluation employed a two-community, time
      series, quasi-experimental design. Annual street surveys samples individuals in
      areas where they were likely to encounter outreach workers. Baseline surveys
      found substantial pre-programmatic behavior change. After two years considerable
      APPLE name recognition (40%), contact with media materials (63%), and contact
      with outreach workers (36%) were found and norms reflecting social acceptability
      of condoms were more positive among women in the intervention community. Condom
      use at last sexual encounter rose in both communities but was significantly
      higher in the intervention community. Condom use also was higher among women who
      reported exposure to either small media or small media plus street outreach.
      Other self-reported HIV-prevention behaviors did not show change in the initial
      period.

PMID- 7646947
TI  - Harnessing the heightened public awareness of celebrity HIV disclosures: "Magic"
      and "Cookie" Johnson and HIV testing.
AB  - This article investigates the impact NBA basketball star Earvin ("Magic")
      Johnson's HIV disclosure had on changes in demand for HIV counseling and testing
      services in New York State's 61 Anonymous HIV Counseling and Testing sites.
      Interrupted time-series analyses were conducted on weekly data from over 34,000
      clients seeking anonymous HIV counseling and testing services from January 1991
      to June 1992, to determine whether demand for these services changed as a result
      of the disclosure. Results indicated that immediately following the HIV
      disclosure, there was a substantial increase in service demand, which transcended
      all sex, race, age, and most HIV risk-related boundaries. Seven months later,
      demand had not returned to pre-disclosure levels. The strong impact on females,
      coupled with additional data analyses in obstetrical settings, suggests that
      previous research has been too narrow in focus, and that the effect of Johnson's
      HIV disclosure has been enhanced, in part, by the publicity surrounding his wife
      and baby. The importance of harnessing the heightened public awareness of
      celebrity HIV disclosures is discussed.

PMID- 7646948
TI  - AIDS prevention for African-American and Latina women: building culturally and
      gender-appropriate intervention.
AB  - African-American and Latino women are at high risk of HIV infection through
      heterosexual transmission, reflected in the significant increases in reported
      AIDS cases of women thus infected. Few AIDS-prevention programs have addressed
      this risk for women by directly, separately and, in appropriate ways, focusing on
      specific women's issues of gender roles, sexuality, and differential power
      relationships with men, in the context of racial and class relations, as these
      affect HIV transmission. This article discusses the contributions of a community
      based AIDS-prevention program to the development of culturally and gender
      appropriate intervention for African-American and Latina women at high risk.
      Further such programs are needed which build on the use of ethnic cultural
      concepts, racial and other social relations, and acknowledge issues specific to
      minority women in order to prevent their infection with HIV.

PMID- 7646949
TI  - Trends in risk behaviors for HIV infection among U.S. high school students, 1989
      1991.
AB  - The objective of this study was to examine trends in rates of self-reported HIV
      related instruction and behaviors among high school students in the United
      States. Self-administered questionnaires were completed by three independent,
      multistage national probability samples of public and private school students in
      grades 9 through 12 who were surveyed in the spring of 1989, 1990, and 1991,
      respectively. Controlling for demographic characteristics, we used logistic
      regression to test for trends from 1989 to 1991. From 1989 to 1991, the
      proportion of students who had received HIV instruction in school significantly
      increased from 53.7% in 1989 to 83.3% in 1991. At the same time, the proportion
      of students engaging in selected sexual behaviors generally decreased. We found
      significant declines in the proportion of students who had engaged in sexual
      intercourse (58.5% in 1989 to 54.1% in 1991), had two or more sex partners during
      their lifetime (40.1% in 1989 to 35.2% in 1991), and had four or more lifetime
      sex partners (23.6% in 1989 to 18.7% in 1991). School-based HIV instruction,
      which is reaching greater numbers of U.S. students, may be contributing to the
      decline in reported risk behavior. However, because the current level of HIV
      related behavior is still too high, risk-reduction efforts for adolescents should
      be maintained and strengthened.

PMID- 7646950
TI  - The relationship of substance use with sex to the use of condoms among young
      adults in two urban areas of Scotland.
AB  - The relationship of the use of alcohol or drugs in conjunction with sexual
      activity and the use of condoms and other contraceptives was examined among 1378
      respondents in a household survey of two urban areas of Scotland. In bivariate
      analyses, respondents who reported having had sex under the influence of alcohol
      or drugs were no less likely than respondents with no such experience to report
      consistent use of condoms, and having had sex under the influence of substances
      was positively related to lifetime condom use. Multivariate analyses that
      included gender and urban area as predictors yielded similar findings. The
      results suggest that individuals who combine sex with alcohol or drugs are not
      necessarily more likely to engage in riskier sex.

PMID- 7646952
TI  - Outbreak of Ebola hemorrhagic fever--Zaire, 1995.

PMID- 7646951
TI  - Epidemiology and health services management.

PMID- 7646953
TI  - Quality of life hinges on thymus.

PMID- 7646954
TI  - Studies show benefits of nurse practitioners.

PMID- 7646955
TI  - Pressure on prison nurses from non-qualified staff.

PMID- 7646956
TI  - Secret success.

PMID- 7646957
TI  - School's out ... for family planning.

PMID- 7646958
TI  - Paying lip service.

PMID- 7646959
TI  - A critical appraisal of preceptorship.
AB  - Preceptorship is a concept which has been wholeheartedly endorsed by the UKCC. On
      the evidence of a proliferating body of literature on the subject, it also has
      wider approbation. This article questions the foundation of the UKCC's concept of
      preceptorship and examines the implications for nurses of uncritical acceptance
      of five assumptions, perceived by the author to be inherent in the UKCC's
      definition.

PMID- 7646960
TI  - Shifting the patterns of nurses' work.
AB  - Although most nurses tend to work a three shift pattern of 'earlies', 'lates' and
      'nights', increasing interest is being shown in the use of 12-hour shift
      patterns. James Buchan outlines the advantages and disadvantages of this type of
      work for both patients and nurses.

PMID- 7646961
TI  - Nurse shortages are now a world-wide problem.

PMID- 7646962
TI  - Reflective practice.

PMID- 7646963
TI  - Going soft?

PMID- 7646964
TI  - Special pleading?

PMID- 7646965
TI  - The last-stop shop.

PMID- 7646967
TI  - Presenting a united front.

PMID- 7646966
TI  - The need to co-ordinate wound care.

PMID- 7646968
TI  - Integrating wound care across a trust.

PMID- 7646969
TI  - Jury still out on new review body chair.

PMID- 7646970
TI  - A break with Bottomley?

PMID- 7646972
TI  - Going it alone?

PMID- 7646973
TI  - Collaborative caring.

PMID- 7646971
TI  - Helpline success leads to plans for counselling service.

PMID- 7646974
TI  - Understanding the principles of traction.
AB  - As the use of traction has declined in recent years, nurses' skills in this area
      have consequently decreased. Standards of care for patients in traction might now
      be called into question. This article attempts to redress this imbalance by
      describing the principles behind safe and effective traction.

PMID- 7646975
TI  - Reflective practice: implementing theory.
AB  - Last week, we looked at the theories and models of reflective practice, in a
      continuing education article. This week, we present a practical example of the
      introduction, implementation and evaluation of reflection and reflective practice
      on an acute mental health admission unit. Practitioners used a variety of
      strategies to increase their awareness of reflective practice, and the author
      details their analysis and subsequent actions following completion of the
      project.

PMID- 7646976
TI  - Nurse practitioners (NPs) from both sides of the Atlantic.

PMID- 7646977
TI  - A multiprofessional approach to audit.
AB  - This article presents the case for a co-operative approach to audit that includes
      input from a range of healthcare professionals. Evaluating the obstacles which
      have prevented such an approach already being in place, the author outlines the
      basis of and benefits to be gained from multiprofessional audit.

PMID- 7646978
TI  - A measurement tool for assessing stress among mental health nurses.
AB  - There is growing evidence that nursing is a stressful occupation, particularly
      mental health nursing. However, the lack of an appropriate measurement tool has
      meant it has been difficult to investigate the nature of this stress. The aim of
      this study was to assess the efficacy of one such scale for measuring stress in
      mental health nurses, the Mental Health Professional Stress Scale. A total of six
      questionnaires was sent to a sample of 210 community and hospital mental health
      nurses. The findings suggested that the scale was a useful measure and predictor
      of stress. The most consistent predictor of poor mental health outcomes for
      nurses was home/work conflict, outweighing the significance of client/patient
      related difficulties.

PMID- 7646979
TI  - Arrested development.

PMID- 7646980
TI  - Changing times.

PMID- 7646982
TI  - All in a night's work.

PMID- 7646981
TI  - Just for the record?

PMID- 7646983
TI  - Healthy scepticism.

PMID- 7646984
TI  - Not another lymphoma classification!

PMID- 7646985
TI  - Why do so many haemophilia A patients develop an inhibitor?

PMID- 7646986
TI  - Chimaeric cultures of human marrow stroma and murine leukaemia cells: evidence
      for abnormalities in the haemopoietic microenvironment in myeloid malignancies
      and other infiltrating marrow disorders.
AB  - PGM-1 is a transplantable C3H/HeJ leukaemia which is not viable in unstimulated
      in vitro culture, differentiates into mature granulocytes and macrophages in
      response to soluble cytokines, and undergoes self-renewing cell divisions in
      coculture with selected human bone marrow stromal cell lines. When PGM-1 cells
      were cultured on pre-established adherent layers from primary human marrow
      samples, their fate depended on the source of the human marrow. Adherent layers
      from healthy marrow donors or patients with reactive marrow alterations had no or
      very little capacity to maintain PGM-1 cells in an immature colony-forming state.
      However, in coculture with adherent layers from patients with myeloid leukaemia
      or, to a lesser extent, lymphoblastic leukaemia or marrow-infiltrating lymphoma
      the colony-forming potential was retained. There was no correlation between the
      remission status of the patient and the PGM-1 activity of the adherent layer.
      Consistent morphological differences between active and inactive stromal layers
      were not observed. The PGM-1 coculture system enables the detection of a hitherto
      undescribed regulatory abnormality in bone marrow malignancies. Whether the PGM-1
      supporting activity is mediated through differences in the production of a
      cytokine with close homology to complement factor Bb which has recently been
      shown to induce self-renewal in immature PGM-1 cells, requires further
      investigation.

PMID- 7646987
TI  - Propagation of large numbers of cells of a human mixed-lineage T
      lymphoid/myeloid.
AB  - Previously, a subset of T cells co-expressing the myeloid antigen CD33 has been
      described in patients with acute myelogenous leukaemia. However, normal
      lymphocytes have been viewed as not expressing the CD33 antigen. We have
      developed culture conditions which allow for the rapid expansion of CD3+CD33+
      cells from patients with myeloid leukaemia as well as normal individuals. The
      protocol for cellular expansion includes the addition of interferon-gamma on day
      0, interleukin-1, interleukin-2 and a monoclonal antibody against CD3 on day 1 to
      peripheral blood lymphocytes. Using this protocol, total cell number increased
      more than 600-fold within 16 d of culture. Cells could be kept in culture for
      more than 6 months. Cells of the CD3+CD33+ phenotype increased to 15.2 +/- 4.6%
      using this protocol after 16 d in culture. These cells have been characterized by
      flow cytometry and have been found to express the alpha, beta T-cell receptor, co
      express the CD2, CD5, CD7 and HLA-DR antigens and did not express CD14 or CD15
      antigens. Cells of the CD3+CD33+ phenotype were unable to lyse tumour cells as
      determined in a 51Cr release assay. In patients with chronic myeloid leukaemia.
      CD3+CD33+ cells seem to be negative for expression of bcr/abl transcript in
      contrast to CD33- cells. Our data suggest that CD3+CD33+ cells do exist in
      peripheral blood from normal individuals.

PMID- 7646988
TI  - IL-3 is produced by normal stroma in long-term bone marrow cultures.
AB  - Interleukin-3 (IL-3) has been shown to have significant effects on haemopoiesis
      in vitro, but early investigations of normal human long-term bone marrow cultures
      (LTBMC) have failed to demonstrate IL-3 production by stromal cells, either by
      Northern blotting for mRNA, or assaying for bioactivity in culture supernatants.
      One recent report, using reverse transcription-polymerase chain reaction (RT
      PCR), demonstrated IL-3 expression in only one of eight cultures. We have
      developed a sensitive bioassay for the detection of IL-3 production from normal
      stroma in LTBMC. LTBMC were grown until confluent, irradiated, and stroma
      harvested by trypsinization to yield single-cell suspensions. These cells were
      then cocultured with target bone marrow mononuclear cells (BMMC), or CD34+ cells
      in clonogenic assays, either in the presence or absence of anti-IL-3 neutralizing
      antibodies. We have demonstrated IL-3 production in 32/34 cases. In addition, by
      separating stroma from target cells using cell culture inserts, we have shown
      that direct stroma:stem cell contact is not necessary for colony growth,
      suggesting that IL-3 diffuses into the supernatant. However, when supernatants
      from LTBMC were assayed by enzyme-linked immunoassay (ELISA), no IL-3 was
      detected. This suggests that IL-3 is probably produced at low levels and has a
      short-range interaction. Stroma production of IL-3 was confirmed by the detection
      by RT-PCR of IL-3 mRNA in 3/3 cases. The simultaneous detection of CD2 mRNA
      demonstrated that T cells are part of the bone marrow stroma. It is therefore
      possible and probably likely that these cells are the source of IL-3.

PMID- 7646989
TI  - Chronic active Epstein-Barr virus disease in a case of persistent polyclonal B
      cell lymphocytosis.
AB  - Persistent polyclonal B-cell lymphocytosis (PPBL) is a rare haematological
      disorder. It is characterized by activated and morphologically atypical B
      lymphocytes and polyclonal IgM production and has been associated with female
      sex, cigarette smoking, and HLA-DR7 expression. We report a case of PPBL with
      intermitting symptoms compatible with a chronic fatigue syndrome, recurrent
      erythema nodosum and multiforme. Serological findings suggested a chronic active
      Epstein-Barr virus (EBV) infection. Messenger RNA of EBV immediate early gene
      transactivation BZLF1 was detected in peripheral blood lymphocytes by reverse
      transcriptase PCR indicating a persistent replication of the virus. Over 2 years
      of observation we detected varying numbers of atypical lymphocytes. These cells
      hybridized with a probe specific for the EBV internal repeat region (BamHI W)
      which indicates a productive infection. Of interest, no reaction was observed
      with a probe specific for the latency-associated small RNAs (EBERs). The
      immunological phenotype of the polyclonal B cells was similar to B-cell lines
      immortalized by EBV in vitro, expressing a number of activation molecules (CD23,
      CD25, CD54) and the bcl-2 protein. In summary, our findings suggest that
      persistent EBV replication might be crucial in the development of
      lymphoproliferative disorders such as PPBL.

PMID- 7646990
TI  - Role of Epstein-Barr virus and soluble CD21 in persistent polyclonal B-cell
      lymphocytosis.
AB  - The expression of EBV proteins and immunological properties were studied in the
      first stable cell line (SM) established from a patient presenting with persistent
      polyclonal B-cell lymphocytosis (PPBL). SM cells which represent a small
      population of EBV-positive atypical cells found in the peripheral blood of the
      patient express the KI-1 antigen (CD30) as well as the proto-oncogene bcl-2
      product and cell surface markers of mature activated B lymphocytes. The cells
      harbour an EBV subtype A genome and contain EBNA2 protein. This argues against a
      transformation-incompetent virus as the main cause of the chronic active EBV
      infection observed in our patient. Latent membrane protein (LMP1) was weakly
      expressed and found predominantly in a perinuclear localization, a location which
      could lead to decreased immunogenicity in vivo. Similar to the EBV-transformed
      marmoset cell line B95-8, SM cells were in part productively infected as
      transcription of the immediate early gene BZLF1 could be shown and in some cells
      high levels of EBV-genome were detected by in situ hybridization with a BamH1 W
      probe. Comparable to the atypical cells in the peripheral blood of the patient.
      EBV small RNAs were not detected with EBER-specific probes. Of interest, we
      noticed a markedly increased production of soluble CD21 (sCD21) antigen by SM
      cells as compared to LCL-type Burkitt's lymphoma cell lines. This could explain
      the elevated sCD21 levels observed in the serum of our PPBL patient and confirms
      our previous findings in patients with acute EBV infection. It also suggests a
      possible role of sCD21 in EBV-mediated regulation of the immune response and
      provides a possible explanation for the dysregulation of the humoral immune
      system observed in PPBl patients.

PMID- 7646991
TI  - Influence of white blood cells on the fibrinolytic response to sepsis: studies of
      septic patients with or without severe leucopenia.
AB  - In septic patients capable of normal white cell responses, high plasma levels of
      PAI-I, t-PA antigen and t-PA-PAI-I complex were observed. The ratios of t-PA and
      PAI-I were such that free PA activity was almost never observed. In patients
      severely leucopenic prior to becoming septic the changes were significantly less
      marked, so presence of leucocytes enhances the fibrinolytic inhibition occurring
      in sepsis. The non-leucopenic septic group showed greater evidence of thrombin
      generation in that FPA levels were higher but fibrinogen levels were only
      slightly less and antithrombin levels not different from those in the leucopenic
      group. A greater tendency to fibrin deposition and the striking fibrinolytic
      inhibition noted in patients with normal white cell responses may contribute to
      the development of some of the complications of sepsis in which fibrin deposition
      participates and may explain their relative rarity in leucopenic patients. When
      shock supervened, levels of PAI-I were high in both leucopenic and non-leucopenic
      groups, indicating that a source of PAI-I outwith the leucocytes themselves
      contributes to the phenomena observed.

PMID- 7646992
TI  - Clonal B-cell expansions in peripheral blood of HCV-infected patients.
AB  - Clonal expansions of IgM-producing B cells were investigated in 38 patients with
      a chronic hepatitis C virus infection. Eight patients were affected with type II
      mixed cryoglobulinaemia (two of whom also had non-Hodgkin's lymphoma and one had
      Waldenstrom's disease), one with type III mixed cryoglobulinaemia, one with
      Waldenstrom's disease, and 28 with chronic liver disease. To detect the clonal B
      cell expansions we used a RT/PCR procedure in which the CDR3/FW4 regions of the
      IgM heavy chain mRNAs were amplified and resolved in sequencing polyacrylamide
      gels. Clonal Ig gene rearrangements were detected in all patients with type II
      mixed cryoglobulinaemia and also at a high frequency (24%) in the HCV-infected
      patients without cryoglobulinaemia. A polyclonal pattern was present in the
      patient with type III mixed cryoglobulinaemia and in the 15 normal individuals
      and 16 age-related patients with HCV-negative alcoholic liver disease which were
      investigated as controls. No association was found between the presence of a
      clonal B-cell expansion and age, sex, liver histology, or levels of serum
      aminotransferase. The serum levels of rheumatoid factor were increased in all
      patients with a clonal expansion, suggesting that the expanded B-cell clones
      belong to the rheumatoid factor producing B-cell subset.

PMID- 7646993
TI  - Ethnic distribution of allele alpha LELY, a low-expression allele of red-cell
      spectrin alpha-gene.
AB  - Allele alpha LELY is a low-expression allele of erythroid spectrin alpha-chain.
      It carries mutations both in exon 40 and intron 45 and is associated with partial
      skipping of exon 46. Allele alpha LELY remains asymptomatic by itself. In
      contrast, it enhances the expression level of deleterious alpha-alleles occurring
      in trans, and as such has clinical importance. The aim of this study was to
      evaluate the incidence of allele alpha LELY in various ethnic groups, i.e.
      Caucasians, African Blacks, Japanese and Chinese. Allele alpha LELY occurred in
      all groups investigated with a fairly uniform frequency: 31%, 21%, 20% and 22%,
      respectively. Mutations in exon 40 and intron 45 appeared linked to one another
      without exception. Partial skipping of exon 46 or the low-expression feature,
      whenever they could be assessed, were invariably observed. Allele alpha LELY
      appears to be an ancient and stable allele.

PMID- 7646994
TI  - Hydroxyurea therapy in beta-thalassaemia intermedia: improvement in
      haematological parameters due to enhanced beta-globin synthesis.
AB  - The beta-thalassaemias represent a heterogenous group of diseases resulting from
      decreased erythroid beta-globin mRNA expression and imbalanced alpha/beta-globin
      chain synthesis which are manifest clinically by ineffective erythropoiesis and
      excessive haemolysis. Increasing levels of haemoglobin F (HbF) by pharmacological
      agents has been proposed to ameliorate the severity of the disease by improving
      the balance in globin chain synthesis. Hydroxyurea (HU), as an effective agent
      with low toxicity for activating gamma-globin gene, has been shown to enhance HbF
      synthesis in experimental animals and in patients with sickle cell anaemia.
      However, previous trials of HU in beta-thalassaemia patients are ambiguous, with
      a small number having increased HbF synthesis. In a recent study of HU effects in
      Chinese beta-thalassaemia patients we unexpectedly found that two unrelated
      patients with beta-thalassaemia intermedia demonstrated an improvement in the
      effectiveness of erythropoiesis reflected by an increase in haemoglobin
      concentration (from 4.1 to 6.3 g/dl, patient 1; from 6.5 to 9.7 g/dl, patient 2)
      and in red cell volume (from 68 to 104 fl, patient 1; from 68 to 85 fl, patient
      2) after a period of excess of 300d of low-dosage HU treatment. These effects,
      however, appear to be due to increased beta-globin biosynthesis, because the
      percentage of HbF decreased in each patient as total Hb increased. This was
      reflected by changes in the beta/alpha ratio (from 0.301 to 0.581, patient 1;
      from 0.348 to 0.487, patient 2) with minimal changes in gamma-globin
      biosynthesis. We conclude that in addition to its known effects in stimulating
      gamma-globin production, hydroxyurea may have a more general role in augmenting
      globin synthesis, including beta-globin in some thalassaemia intermedia patients
      who maintain the capacity to express normal beta-globin chains.

PMID- 7646995
TI  - Detection of beta-thalassaemia mutations using DNA heteroduplex generator
      molecules.
AB  - In this report we describe a rapid polymerase chain reaction (PCR) based method
      for the detection of beta-thalassaemia (beta-thal) mutations. This method is
      based on the visualization of unique DNA heteroduplex banding patterns, following
      non-denaturing polyacrylamide gel electrophoresis, resulting from hybridization
      between mutant PCR products and synthetic DNA heteroduplex generator molecules.
      Using the Singaporean population, which consists of Chinese, Malay and Asian
      Indian ethnic groups, as a model, we have constructed and evaluated three DNA
      heteroduplex generator molecules for the detection of the common beta
      thalassaemia mutations found in this population. The results show that these
      three molecules are capable of detecting approximately 95% of the mutations found
      in the Singaporean population. We propose that this technology may be applied as
      an alternative screening strategy for beta-thalassaemia mutations because it is
      technically simple, flexible, cost-effective, and requires only minimal
      laboratory resources.

PMID- 7646996
TI  - Differential sensitivity of CD30+ neoplastic cells to gelonin delivered by anti
      CD30/anti-gelonin bispecific antibodies.
AB  - Lymphocyte activation antigens, such as CD30, represent suitable target molecules
      for antibody-driven drug delivery in haemopoietic malignancies. A ribosome
      inactivating protein (RIP) type 1 of potential interest for mAb targeting is
      gelonin, which displays a lower toxicity, as compared to other RIPs. In this
      study, two anti-CD30/antigelonin bispecific monoclonal antibodies (bimAbs),
      secreted by hybrid hybridomas, were used to deliver this RIP to CD30+ tumour
      cells. The two bimAbs, termed D4 and A18, were produced using the same anti-CD30
      mAb and two anti-gelonin mAbs, directed to unrelated epitopes of the gelonin
      molecule. These bimAbs enhanced gelonin toxicity (IC50 5 x 10(-8) M, in the
      absence of mAbs) against the CD30+ L540 Hodgkin's lymphoma cell line in a protein
      synthesis inhibition assay. Thus, in the presence of 10(-9) M D4 bimAb, protein
      synthesis was inhibited with an IC50 of 5 x 10(-10) M as gelonin, whereas with
      A18 bimAb the IC50 was 8 x 10(-11) M. More interestingly, the combined use of the
      two bimAbs had a synergistic effect, since the IC50 of gelonin reached 6 x 10(
      12) M. Among CD30 tumour cell lines, the Hodgkin's lymphoma L428 was also
      sensitive to gelonin delivered by bimAbs (IC50 6 x 10(-11) M), whereas the COLE
      Hodgkin's cell line and the T-ALL Jurkat were completely resistant to the toxic
      effect of gelonin and bimAbs. COLE and Jurkat cells were also resistant to a
      gelonin/anti-CD30 conventional immunotoxin, whereas they were sensitive to a
      saporin/anti-CD30 immunotoxin. This suggests that the resistance to gelonin is
      not related to a lack of internalization through the CD30 molecule but is
      associated with some property of the RIP.

PMID- 7646997
TI  - The detection of clonal proliferation in granular lymphocyte-proliferative
      disorders of natural killer cell lineage.
AB  - The clonal proliferation of large granular lymphocytes can be detected in
      patients with T-cell-lineage granular lymphocyte-proliferative disorders (T-GLPD)
      by Southern blotting T-cell receptor genes. However, this cannot be applied to
      patients with natural killer-cell-lineage GLPD (NK-GLPD) as it lacks a clonal
      marker. We therefore investigated the use of two other diagnostic techniques in
      evaluating clonal proliferation in Japanese patients with NK-GLPD (n = 4) and T
      GLPD (n = 3) by chromosomal analysis of peripheral blood mononuclear cells (PBMC)
      stimulated with either interleukin-2 or phytohaemagglutinin, and Epstein-Barr
      viral (EBV) genomic DNA analysis. Chromosomal analysis revealed abnormal
      karyotypes in the PBMC of three of four patients with NK-GLPD, whereas EBV
      analysis showed a monoclonal terminal configuration in the PBMC in the fourth
      patient. Southern blots revealed rearrangements of the TCR genes in all three
      patients with T-GLPD but in none of those with NK-GLPD. It is suggested that
      these methods may be useful in detecting the abnormal proliferation of large
      granular lymphocytes in NK-GLPD.

PMID- 7646998
TI  - Diverse expression of cytosolic phospholipase A2, 5-lipoxygenase and
      prostaglandin H synthase 2 in acute pre-B-lymphocytic leukaemia cells.
AB  - Several lines of evidence suggest that phospholipases A2, leukotrienes and
      prostaglandins play a role in the proliferation of haemopoietic cells. The
      expression of genes involved in the biosynthesis of leukotrienes and
      prostaglandins was investigated in peripheral B lymphoblasts, isolated from eight
      patients with acute pre-B-lymphocytic leukaemia (pre B-ALL). RT-PCR analysis
      demonstrated that four of the investigated pre-B-ALL clones expressed the gene
      coding for cytosolic phospholipase A2 (cPLA2), but not the gene coding for 5
      lipoxygenase. In contrast, the remaining four pre-B-ALL clones expressed 5
      lipoxygenase but not cPLA2, suggesting that the transcriptional regulation of
      these two genes are different and that their cellular functions are not linked to
      each other. The capacity of pre B-ALL cells to produce LTB4 and to express the 5
      lipoxygenase protein, correlated with the expression of 5-lipoxygenase mRNA. All
      pre-B-ALL clones expressed genes coding for 5-lipoxygenase activating protein
      (FLAP), leukotriene A4 hydrolase and prostaglandin (PG)H synthase 1. Seven of the
      eight pre B-ALL clones expressed PGH synthase 2. In comparison, normal tonsillar
      B cells did not express cPLA2 or PGH synthase 2.

PMID- 7646999
TI  - Allogeneic marrow grafts from donors with congenital chromosomal abnormalities in
      marrow cells.
AB  - To determine whether siblings with chromosomal abnormalities in marrow cells
      which are associated with cellular defects (e.g. Down syndrome or heterozygosity
      for Fanconi syndrome) are suitable donors for allogeneic bone marrow transplants,
      we have reviewed the patient files at the Fred Hutchinson Cancer Research Center
      (FHCRC) and carried out a survey among member centres of the International Bone
      Marrow Transplant Registry (IBMTR). The 57 of 253 (23%) member centres which
      responded to the survey reported seven transplants from donors with the following
      conditions: Down syndrome (n = 2), suspected heterozygotes for Fanconi syndrome
      (n = 3), and 47,XXX syndrome (n = 2), among a total of 5,561 allogeneic
      transplants from HLA-identical siblings. Adding the three cases seen at the Fed
      Hutchinson Cancer Research Center among 2,927 HLA-identical sibling transplants
      during 1992 resulted in 10 transplants among 8,488 cases transplanted overall:
      four with Down syndrome, four suspected of being heterozygous for Fanconi
      syndrome, and two trisomy X. Three out of four grafts from siblings with Down
      syndrome had complications, including poor graft function (n = 2) and graft
      failure (n = 1). Two of four recipients of marrow from presumed Fanconi syndrome
      heterozygotes presented with poor graft function and a third recipient developed
      graft failure after initial evidence of engraftment. The two patients given
      marrow from siblings with 47,XXX syndrome engrafted uneventfully. The experience
      reported here shows a low frequency of encountering an HLA-identical sibling
      donor who has chromosomal abnormalities in marrow cells consistent with Down
      syndrome or heterozygosity for Fanconi syndrome, about one case among 1,000
      transplants. The much higher than expected incidence of graft problems with
      marrow from such a donor would make it reasonable to look either for an
      alternative marrow donor or consider an autologous transplant, in case a sibling
      marrow donor with Down syndrome or heterozygosity for Fanconi syndrome is
      encountered, although a donor with trisomy X seems acceptable.

PMID- 7647000
TI  - The myelodysplastic syndromes: an analysis of prognostic factors in 226 cases
      from a single institution.
AB  - Two hundred and twenty-six patients were diagnosed with myelodysplastic syndrome
      (MDS), according to the French-American-British (FAB) criteria, over a 13-year
      period, and studied retrospectively in a single institution in order to study
      indicators which were prognostically significant. Analysis of clinical and
      laboratory data indicated that the FAB classification, the Bournemouth,
      Dusseldorf, Goasguen, Sanz and FAB Scoring Systems were all good predictors of
      survival. We found advancing age, haemoglobin (Hb) < or = 9 g/dl, platelet count
      < or = 50 x 10(9)/l, increased peripheral total white cell count (WCC) and
      monocytosis, increased bone marrow blasts, dysgranulopoiesis, and bone marrow
      fibrosis were significant adverse prognostic variables. The commonest
      complication and cause of death was infection; however, infective episodes were
      not significantly associated with low neutrophil counts (either < or = 1.5 x
      10(9)/l or < or = 0.8 x 10(9)/l) and there was also no significant association
      between neutropenia and survival. These findings indicate that neutrophil
      dysfunction plays an important role in the clinical progression of patients with
      MDS. The effect of new therapeutic modalities, such as the haemopoietic growth
      factors, on reducing infective episodes may be as significant as their effect on
      increasing neutrophil counts.

PMID- 7647002
TI  - Persistence of RAR alpha-PML fusion mRNA detected by reverse transcriptase
      polymerase chain reaction in patients in long-term remission of acute
      promyelocytic leukaemia.
AB  - Acute promyelocytic leukaemia (APL) is characterized by t(15;17), which results
      in the formation of two chimaeric genes, PML-RAR alpha and RAR alpha-PML. PML-RAR
      alpha transcripts have been detected in all cases of APL whilst those of RAR
      alpha-PML have been detected in only about 67% of cases. We have used reverse
      transcriptase polymerase chain reaction (RT-PCR) to detect both fusion
      transcripts serially in 18 patients in remission of APL after chemotherapy and
      bone marrow transplantation. All patients were negative for PML-RAR alpha,
      whereas in six patients (remission 3-9 years) RAR alpha-PML was consistently
      detected. Only one patient at remission showed the 5' breakpoint RAR alpha-PML,
      with the rest showing the 3' breakpoint 144 bp RAR alpha-PML. The level of
      sensitivity for detecting RAR alpha-PML was some 10-fold higher than that for PML
      RAR alpha. Serial negative tests for PML-RAR alpha have been correlated with
      durable remissions, suggesting possible eradication of residual leukaemia in APL.
      Our results, however, show persistence of t(15;17) cells expressing RAR alpha-PML
      fusion mRNA in patients in long-term remission of APL. They indicate that
      patients considered clinically 'cured' of APL still have molecular evidence of
      minimal residual disease and also provide further insight into the biology of
      acute myeloid leukaemia.

PMID- 7647001
TI  - Expression of erythroid-specific genes in acute megakaryoblastic leukaemia and
      transient myeloproliferative disorder in Down's syndrome.
AB  - Acute megakaryoblastic leukaemia (M7) and transient myeloproliferative disorder
      in Down's syndrome (TMD) are characterized by rapid growth of abnormal blast
      cells which express megakaryocytic markers. To clarify properties of the blast
      cells in M7 and TMD cases, we examined erythroid markers expression in blasts
      from six cases with M7 and seven cases with TMD in this study. Erythroid-specific
      mRNAs encoding gamma-globin and erythroid delta-aminolevulinate synthase were
      found to be expressed in blasts from most of these cases, indicating that
      majorities of the blasts in M7 and TMD cases have erythroid and megakaryocytic
      phenotypes. We also found that mRNAs encoding GATA-1 and GATA-2 are expressed in
      all these cases. These results suggest that M7 blasts and TMD blasts correspond
      to the erythroid/megakaryocytic bipotential progenitor cells.

PMID- 7647003
TI  - Cytogenetic study in multiple myeloma at diagnosis: comparison of two techniques.
AB  - Cytogenetic studies in multiple myeloma (MM) have been disappointing due to the
      low mitotic index of plasma cells. Recently the detection of clonal chromosomal
      abnormalities at diagnosis seemed to be improved by addition of cytokines (IL-6
      and GM-CSF) in the culture medium. We performed two parallel total bone marrow
      cells culture types in 33 stage I, II and III multiple myeloma patients at
      diagnosis: 3 d without any cytokine, and 4-7 days stimulated with IL-6 and GM
      CSF. No clonal chromosomal abnormality was detected in the 12 stage I and II
      patients either in 3 d or in 4-7 d culture. In stage II patients, abnormalities
      were observed in 18/21 (85.7%) and in 8/18 (44.4%) in the 3 d culture and the 4-7
      d stimulated cultures respectively. Our results suggest that in stage III
      multiple myeloma at diagnosis, 3 d culture without cytokine may be the better
      technique to detect clonal chromosomal abnormalities, and, before using cytokines
      as a reference condition, this 3 d unstimulated culture should be considered.

PMID- 7647004
TI  - CD3-induced T-cell activation in the bone marrow of myeloma patients: major role
      of CD4+ cells.
AB  - A large expansion of activated T cells (CD3+CD25+) with the potential to act as
      anti-tumour effector cells is inducible in multiple myeloma (MM) patients by
      culturing bone marrow mononuclear cells (BMMCs) with the anti-CD3 monoclonal
      antibody (mAb) OKT3. The aim of this study was to provide a greater
      characterization of CD3-activated T cells. On day 6, most T cells coexpressed the
      CD11a, CD18, CD54, CD45R0 antigens and consisted of activated (CD25+) CD4+ and
      CD8+ cells in nearly equal proportions. Kinetics studies showed that CD4+CD25+
      cells proliferated more rapidly and peaked earlier than CD8+CD25+ cells. When
      experiments were performed with purified subpopulations by removing CD4+ cells
      (resulting in CD8+ BMMCs) or by removing CD8+ cells (resulting in CD4+ BMMCs). T
      cell activation and autologous plasma cell decrease were observed in CD4+ BMMCs
      only. Transwell cultures showed that CD4 help was necessary to make CD8+ BMMCs
      susceptible to CD3 stimulation. Relevant amounts of IL-2 were found in the
      supernatants of CD4+ BMMCs cultures, whereas no secretion of IL-4 was detected,
      indicating a Th1-like profile of CD3-activated CD4+ cells. These data indicate
      that CD4+ cells proliferate earlier and provide optimal help to induce the
      subsequent expansion of CD8+ cells after CD3 stimulation of MM BMMCs. Adequate
      stimulation of CD4+ cells is therefore essential in any strategy aiming to
      recover T-cell-mediated immunity in MM.

PMID- 7647005
TI  - Redistribution of GPIb/IX and GPIIb/IIIa during spreading of discoid platelets.
AB  - The purpose of the present study was to prelabel mobile receptors on discoid
      platelets with specific ligands identifiable in the electron microscope and
      follow their redistribution during spreading. Platelets were incubated in
      suspension with cytochalasin E (CE) to preserve discoid form, chilled and mounted
      on cold formvar grids or glass slide fragments to inhibit receptor movement,
      covered with cold bovine or ristocetin-activated human plasmas as sources of vWF
      to bind GPIb/IX, fibrinogen-coated gold particles (Fgn/Au) to couple GPIIb/IIIa,
      or both probes simultaneously, washed to remove CE and rewarmed to 37 degrees C
      for intervals up to 30 min to stimulate spreading. After brief fixation grids and
      glass fragments were incubated with anti-vWF antibody and, subsequently,
      staphylococcal protein A coupled to 5 nm and 10 nm gold particles to detect vWF
      multimers. Virtually all of the CE-treated chilled platelets retained their
      discoid shape. Half of the discs (53.3%) bound Fgn/Au, and all bound vWF.
      Receptors for both ligands were randomly dispersed on discoid cells from edge to
      edge. During rewarming discoid platelets expanded into spread forms. Fgn/Au
      GPIIb/IIIa complexes moved into caps over cell centres and into residual channels
      of the open canalicular system (OCS). vWF bound to GPIb/IX moved with the cell
      membrane as the surface expanded during spreading. Discoid platelets prelabelled
      with both ligands demonstrated similar findings. During rewarming Fgn/Au
      GPIIb/IIIa complexes moved to cell centres and into OCS channels. vWF multimers
      bound to GPIb/IX moved apart from each other toward peripheral margins of the
      spread cells. Thus, surface activation resulting in conversion of discoid
      platelets to spread forms does not cause clearance of GPIb/IX receptors to cell
      centres and channels of the OCS in the manner that GPIIb/IIIa receptors coupled
      to Fgn/Au are simultaneously translocated and concentrated in OCS channels.

PMID- 7647006
TI  - Maternal alloimmunization against fetal platelet antigens: a prospective study.
AB  - Neonatal alloimmune thrombocytopenia (NAIT) is induced by maternal alloantibodies
      to fetal platelet antigens. This prospective study was carried out to evaluate
      the incidence of anti-platelet antibodies in 933 mother-child pairs where the
      mother and child were typed for the human platelet antigens (HPA)-1, -2, -3, -5.
      Sera from mismatched mother-child pairs were screened for anti-platelet
      antibodies, anti-HLA class I and blood group ABO IgG antibodies. Platelet
      specific antibodies were anti-HPA-3a in one and anti-HPA-5b in 17 neonates,
      respectively. All these neonates had normal platelet counts. One woman had
      autoreactive antibodies. Anti-HLA class I and anti-blood group A IgG antibodies
      were detected in five and four neonates, respectively, born with a platelet count
      < 150 x 10(9)/l. None of the 11 homozygous HPA-1b mothers became immunized
      against their heterozygous offspring. The maternal HLA-allotypes HLA-DR52 and 
      DR6, typically found in individuals immunized against HPA-1a and -5b,
      respectively, were found in three of 11 HPA-b/b nonresponders and eight of the
      anti-HPA-5b responders. The results indicate that a risk for NAIT due to HPA-2
      and -3 alloimmunization is low. The HLA allotypes do not predict the risk for
      NAIT due to HPA-1 or -5 alloimmunization. Maternal anti-HPA-5b antibodies do not
      correlate with the platelet count in the neonate.

PMID- 7647007
TI  - Absence of incorporation of plasma von Willebrand factor into porcine platelet
      alpha-granules.
AB  - In order to study the relationship between plasma and platelet von Willebrand
      factor (vWF), we used an experimental model of crossed bone marrow
      transplantation (BMT) between SLA immunocompatible normal and homozygous von
      Willebrand (vWD) pigs. A normal pig received bone marrow from a vWD pig and a
      second pig with vWD was engrafted with marrow from a normal pig. Each recipient,
      after total irradiation of 10 Grays, received by a central catheter 10(10)
      monocellular bone marrow cells without immunosuppression. The animals were
      followed for 50 d and no graft rejection or graft-versus-host disease was
      observed. After aplasia occurring 3 weeks after BMT, white blood cells and
      platelets returned to normal. Before transplantation, in the vWD pig, vWFAg and
      vWF activity were not detected in plasma and in platelet and megakaryocyte alpha
      granules. After transplantation with normal marrow, platelet vWFAg and platelet
      vWF activity wer normal and high molecular weight multimers and numerous tubular
      structures were present in alpha-granules. Before transplantation, the normal pig
      had normal plasma and platelet vWFAg-vWF activity, normal multimeric pattern, and
      the platelet and megakaryocyte alpha-granules displayed many tubular structures,
      eccentrically located in one of their poles, coinciding with immunogold staining
      vWFAg. After transplantation with homozygous vWD marrow, platelet and
      megakaryocyte alpha-granules lacked tubular structures. Alpha-granule immunogold
      staining for vWF was consistently negative, although plasma vWF was at a normal
      level. In conclusion, this study shows that, unlike other plasma proteins such as
      fibrinogen. vWF endocytosis does not occur from plasma to the platelet alpha
      granules. Platelet and megakaryocyte vWF solely originates from megakaryocyte
      endogenous synthesis and is independent of plasma vWF.

PMID- 7647008
TI  - Measurement of factor Xa-antithrombin III in plasma: relationship to prothrombin
      activation in vivo.
AB  - The M(r) of the complexes formed when factor Xa reacts with antithrombin III
      (ATIII) in plasma were estimated by gel filtration and SDS-polyacrylamide
      electrophoresis. The predominant species of factor Xa-ATIII detected after plasma
      and plasma to which factor Xa had been added were gel filtered on Sephadex G-200
      and Sepharose 4B had apparent M(r) > 200,000, in which factor Xa-ATIII was
      associated with vitronectin. Addition of factor Xa-ATIII to ATIII-depleted plasma
      also resulted in the formation of factor Xa-ATIII-vitronectin complexes with M(r)
      > 200,000. Using polyclonal antibodies to human factor Xa-ATIII and ATIII as the
      capture and detector antibodies, respectively, a sensitive and specific enzyme
      linked immunosorbent assay was developed to quantify factor Xa-ATIII in plasma.
      The relationship between factor Xa-ATIII production and prothrombinase activity
      in vivo was investigated by quantifying factor Xa-ATIII and prothrombin fragment
      1 + 2 endogenous to the plasmas of blood donors and patients with Hodgkin's and
      non-Hodgkin's lymphoma. Whereas the concentrations of prothrombin fragment 1 + 2
      in the 84 normal plasmas increased with age, those of factor Xa-ATIII (mean +/-
      SD of 34.7 +/- 13.8 pM) did not, and no correlation existed between the
      concentrations of the two parameters in normal plasmas. In contrast, a highly
      significant correlation between the concentrations of these two parameters was
      found in the plasmas of the cancer patients which coincidentally also had higher
      concentrations of both factor Xa-ATIII and prothrombin fragment 1 + 2 than the
      normal plasmas. Thus, ATIII may differentially influence prothrombinase formation
      and activity in normal individuals and cancer patients.

PMID- 7647009
TI  - Ferritin excretion and iron balance in humans.
AB  - Under normal circumstances, most of the lumenal iron taken into the intestinal
      mucosal cell is stored within the cell as ferritin and subsequently is lost in
      the faeces when the cell exfoliates at the end of its lifespan. To evaluate
      whether faecal iron proteins reflect mucosal cell iron as well as whole body iron
      and to examine further the kinetics of gastrointestinal iron transport, faecal H
      rich and L-rich ferritin were measured in normal subjects and patients with iron
      deficiency and genetic haemochromatosis. In normal and iron-deficient subjects,
      the concentration of L-rich but not H-rich faecal ferritin correlated closely
      with body iron status. In genetic haemochromatosis, the faecal L-rich and H-rich
      ferritin concentrations were lower than expected for their body iron status. The
      administration of oral iron to normal subjects led to a rise in L-rich ferritin.
      Administration of oral or parenteral iron to patients with iron deficiency led to
      a prompt rise in both forms of faecal ferritin, although the relative increase of
      L-rich ferritin was greater than that of H-rich ferritin with oral iron
      administration. Faecal ferritin correlated closely with iron stores in normals
      and patients with iron deficiency but faecal ferritin levels were lower than
      expected in genetic haemochromatosis, similar to that previously noted in the
      duodenal mucosal cells of these patients.

PMID- 7647011
TI  - Monoclonal gammopathy of undetermined significance: chromosome changes are a
      common finding within bone marrow plasma cells.
AB  - We used two indirect approaches [image analysis (Feulgen staining) and
      fluorescence in situ hybridization (FISH)] to study bone marrow plasma cells
      (BMPC) in 28 patients fulfilling criteria for MGUS. 61% of patients were found to
      be aneuploid after image analysis: three were hypodiploid and 14 were
      hyperdiploid. 12/14 hyperdiploid patients also revealed abnormalities after FISH:
      12-72% of BMPC exhibited trisomy for at least one of chromosomes 3, 7, 9 and 11.
      These latter chromosomes are the four chromosomes most frequently implicated (in
      the shape of trisomy) in MM, confirming the tight relationship between both
      conditions. After a median follow-up of 19 months (12-41 months) no patient
      developed overt MM. Also, we failed to find any relationship between currently
      available biological parameters and DNA findings. As literature data give a
      transformation rate of 20-30% after a follow-up of 20-35 years, it is worth
      presuming that some aneuploid patients will evolve to MM, whereas others (also
      with aneuploid bone marrow plasma cells) will never develop cancer. Our findings
      indicate that numeric abnormalities, as they are shared both by MGUS and MM
      patients, are certainly an additional or a prerequisite event, but are not
      related to an overt disease. They also emphasize the importance of cytogenetic
      study in the pathophysiology of MGUS.

PMID- 7647010
TI  - A point mutation (Arg271-->Cys) of a homozygote for dysfunctional prothrombin,
      prothrombin Obihiro, which has a region of high sequence variability.
AB  - The molecular defect of a congenitally dysfunctional form of prothrombin,
      prothrombin Obihiro, was identified in a patient with a severe bleeding tendency.
      He showed reduced fibrinogen clotting activity, despite a normal prothrombin
      antigen level. Nucleotide sequencing of amplified DNA revealed a C-->T change at
      nucleotide 7311 of exon VIII of the prothrombin gene. This resulted in the
      substitution of Arg271 by Cys at the factor Xa cleavage site which precludes
      normal activation of prothrombin Obihiro by factor Xa and the generation of
      thrombin. The proband was homozygous for this mutation. In addition, seven new
      nucleotide changes were identified in the prothrombin gene of this patient by
      comparison with the published gene sequence. Three polymorphisms at nucleotides
      4291, 4298 and 7223 were exclusively identified in the prothrombin gene from
      Japanese. Particularly in the region containing exon VI and introns E and F
      (nucleotides 4048-4303), the prothrombin gene proved to be of high-sequence
      variability.

PMID- 7647012
TI  - Trisomy 8 in acute promyelocytic leukaemia: an interphase study by fluorescence
      in situ hybridization.
AB  - Acute promyelocytic leukaemia (APL) is characterized by t(15;17)(q24;q21).
      Trisomy 8 is the commonest accompanying karyotypic aberration. We investigated 14
      APL patients for trisomy 8 using fluorescence in situ hybridization (FISH).
      Conventional cytogenetic analysis showed trisomy 8 in two of nine successfully
      karyotyped cases. With FISH, a possible third case showing a subclone (1-2.5%)
      with trisomy 8 was found. The trisomy 8 clone size defined by karyotyping and
      FISH was concordant in one case and discordant in another, in which trisomy 8 was
      found in 100% of metaphases but only in 48% of leukaemic promyelocytes by FISH.
      Therefore trisomy 8 was mosaic in all the cases, suggesting that it had arisen
      from clonal evolution. All-trans-retinoic acid successfully induced morphologic
      remission in both cases with trisomy 8.

PMID- 7647013
TI  - Combined immunophenotyping and in situ hybridization (FICTION): a rapid method to
      study cell lineage involvement in myelodysplastic syndromes.
AB  - We present a study in which we used a recently described method combining
      fluorescence in situ hybridization (FISH) and immunophenotyping, i.e. FICTION, to
      assess the involvement of different cell lineages in myelodysplastic syndrome
      (MDS) with monosomy 7 (-7), trisomy 8 (+8) or loss of Y chromosome (-Y). Blood or
      marrow smears or cytocentrifuge preparations were stained both by antibodies to
      granulocytes (CD15), monocytes (CD14), T lymphocytes (CD3), B lymphocytes (CD20)
      and by probes specific for chromosomes 7, 8 or Y. Of nine cases of MDS with -7,
      four with +8 and two with -Y studied, none showed lymphocytic involvement by the
      chromosome abnormality. In contrast, -7, +8 and -Y were found in granulocytes and
      monocytes in all patients studied, but they involved a variable proportion of
      those cells. The partial involvement by -7 and +8 seen in some cases suggests
      that myelopoiesis was only partially clonal in those cases, or that the
      chromosome abnormality was a secondary event in the MDS process. FICTION
      therefore appears to be a simple and easily reproducible method that can be used
      for the assessment of lineage involvement in MDS and other haematological
      malignancies.

PMID- 7647014
TI  - The gp 130 family cytokines IL-6, LIF and OSM but not IL-11 can reverse the anti
      proliferative effect of dexamethasone on human myeloma cells.
AB  - In order to understand the mechanisms supporting steroid escape in patients with
      multiple myeloma (MM), three IL-6 autocrine human myeloma cell lines, LP1, OPM2
      and L363, have been treated with dexamethasone in the presence or absence of
      cytokines belonging to the gp 130 family: IL-6, LIF, OSM and IL-11. With
      pharmacological doses of dexamethasone, a dramatic growth arrest was observed in
      all the cell lines. IL-6 completely reversed this inhibition. Of note, this IL-6
      induced reversion was still seen with very low amounts of IL-6 (12 pg/ml).
      Finally, whereas LIF and OSM had clear growth-promoting effects on OPM2 only,
      both cytokines (but not IL-11) reversed the dexamethasone-induced growth arrest
      in all the cell lines. Therefore the high levels of IL-6 (ng/ml) observed in the
      MM intermediate milieu and the putative presence of LIF and OSM can easily
      counteract the effects of dexamethasone in vivo.

PMID- 7647015
TI  - Growth inhibition of leukaemic cells carrying the t(3;21) by the AML1/EVI-1
      specific antisense oligonucleotide.
AB  - The t(3;21)(q26;q22) translocation is thought to play an important role in the
      acute phase transformation of CML. The formation of the AML1/EVI-1 fusion gene by
      the translocation leads to expression of the AML1/EVI-1 fusion protein. Here we
      demonstrate that the AML1/EVI-1-specific antisense oligonucleotide markedly
      decreases the [3H]thymidine incorporation and growth of leukaemic cells carrying
      the t(3;21) and the t(9;22), but not those of K562 cells. These results indicate
      that the AML1/EVI-1 fusion protein could contribute to proliferation of the
      t(3;21)-carrying leukaemic cells after entering the blastic crisis phase of CML.

PMID- 7647016
TI  - Low-intensity oral anticoagulation in sickle-cell disease reverses the
      prethrombotic state: promises for treatment?
AB  - Increased plasma levels of prothrombin fragment 1 + 2 (F1 + 2) found in patients
      with sickle-cell disease reflect enhanced endogenous thrombin generation. We
      postulate that hypercoagulability contributes to vaso-occlusion. The intensity of
      acenocoumarol treatment required to reduce the F1 + 2 level to 50% of
      pretreatment level was investigated in seven patients with symptomatic sickle
      cell anaemia during steady-state disease for a period of 2 months. All patients
      had increased levels of F1 + 2 compared with an age-matched control group.
      Normalization of the F1 + 2 was achieved at a median INR of 1.64 (range 1.18
      2.2). It is concluded that low-intensity oral anticoagulation normalizes the
      hypercoagulability in sickle-cell disease.

PMID- 7647017
TI  - Predicting the severity of haemolytic disease of the newborn: an assessment of
      the clinical usefulness of the chemiluminescence test.
AB  - The ability of the chemiluminescence test (CLT) to predict the severity of
      haemolytic disease of the newborn (HDN) was determined in 80 alloimmunized
      pregnant women who delivered antigen-positive babies. In 54 cases of
      alloimmunization to D, results from the CLT showed better correlation with fetal
      outcome than anti-D concentration measured by AutoAnalyzer (r = 0.70 and 0.36
      respectively). Results from the CLT permitted a threshold level of antibody
      activity (30%) below which 15/20 babies were unaffected or had mild disease, and
      only one required transfusion therapy in utero. CLT results above 30% were
      associated with moderate or severe disease in all cases. Results from the
      AutoAnalyzer proved a less reliable predictor of disease severity; three women
      with anti-D levels > 20 iu/ml delivered unaffected babies, and two women with
      anti-D levels < 10 iu/ml delivered babies who had required transfusion in utero.
      The clinical usefulness of the CLT derives from the possibility of avoiding
      invasive monitoring procedures in women with high levels of anti-D which is
      relatively non-functional.

PMID- 7647018
TI  - Excessive bone resorption in human plasmacytomas: direct induction by tumour
      cells in vivo.
AB  - We studied the bone resorption (BR) in 82 patients with overt plasmacytomas (PCT)
      by histomorphometry. All the solitary PCT and 90% of overt PCT in complete
      remission lacked excessive BR. In contrast, 73% of the 68 patients with active
      overt PCT had an excessive BR. This excessive BR was highly related to the
      presence of tumour cells within the bone sample. Indeed, 92% of patients with
      active PCT and tumour cells within the biopsy had an excessive BR. On the other
      hand, 70% of patients with active PCT but lacking tumour cells within the biopsy
      had normal BR.

PMID- 7647019
TI  - Development of resistance to activated protein C during pregnancy.
AB  - We measured activated protein C (APC) anticoagulant activity in 20 healthy women
      at 14-20, 28 and 36 weeks gestation, and at 1 d post-partum. Significant
      reductions in the mean APC sensitivity ratio (APC-SR) were observed at all stages
      of pregnancy studied compared with the mean APC-SR obtained for baseline
      measurements carried out at > 8 weeks post-partum. APC resistance was seen in
      8/19 (42%) and in 11/20 (55%) women at 14-20 and 28 weeks gestation respectively.
      The development of resistance to APC may contribute to the increased risk of
      thrombosis during pregnancy.

PMID- 7647020
TI  - Serum IL-6 concentrations in lymphomas.

PMID- 7647021
TI  - Emergence of karyotypically unrelated clones in remission of de novo acute
      myeloid leukaemia.

PMID- 7647022
TI  - Pharmacology of the potassium channel openers.
AB  - The potassium-channel openers comprise a large number of molecules that can be
      classified into three basic groups: (1) agents like levcromakalim that open a
      small-conductance (10-30 pS) glibenclamide-sensitive K+ channel currently known
      as the ATP-sensitive K+ channel, KATP; (2) hybrid molecules, such as nicorandil,
      that open KATP channels and that also activate the enzyme-soluble guanylate
      cyclase; (3) molecules like dehydrosaponin 1 that open the large-conductance (100
      150 pS) calcium-dependent K+ channel, BKCa. K(+)-channel openers in groups 1 and
      2 are most potent on smooth muscle, but KATP channels in cardiac muscle, neurones
      and the pancreatic beta cell are also affected. In vivo, moderate to high doses
      produce a fall in diastolic pressure with reflex tachycardia; low doses may exert
      selective dilator effects on specific vascular beds with little effect on
      systemic pressure. In vitro, all smooth muscles are relaxed with loss of
      spontaneous electric and mechanical activity; hyperpolarization to the region of
      EK is often observed. These effects can be antagonized by glibenclamide and also
      by imidazolines and guanidines, such as phentolamine, guanethidine, and
      antazoline, agents that also inhibit the smooth muscle delayed rectifier channel,
      KV. The mode and site of action of the group 1 and 2 K(+)-channel openers is the
      subject of intense study. Irrespective of their specific mode of action, the K(+)
      channel openers, especially the hybrid molecules such as nicorandil, constitute a
      novel and promising approach to the treatment of cardiovascular disease.

PMID- 7647024
TI  - Effects of nicorandil on regional perfusion and left ventricular function.
AB  - Left ventricular function and regional perfusion were evaluated by two study
      designs in patient groups with stable ischemic coronary artery disease (CAD): (1)
      using conventional left ventricular angiographies and (2) applying myocardial
      contrast echocardiography. The aim of the studies was to establish the effects of
      sublingually or orally applied nicorandil (N) on pacing-induced myocardial
      ischemia (MIS). In the first angiographic study, in nine patients with ischemic
      CAD and with pacing-inducible MIS, the effect of N, 20 mg sublingually, on
      hemodynamics and regional wall motion (RWM) were studied. There were no parameter
      changes without MIS being induced when comparing measurements at the 7th and 14th
      minute after N application to control values (p > 0.05). In the 15th and 16th
      minutes after N, pacing-induced MIS could no longer be elicited but left
      ventricular pump function improved; comparing MIS with N versus MIS without N:
      ejection fraction improved by 21%, cardiac index by 37%, and RWM by 21%, while
      filling pressure fell by 41% and systemic vascular resistance fell by 29%. Thus,
      N-mediated "protection from ischemia" with rather improved hemodynamics and RWM
      corresponds with alterations that theoretically could have been expected after
      nitroglycerin given under the above conditions. In the second echocardiographic
      study, regional perfusion was assessed in 10 patients by intracoronary injection
      of a newly developed echo contrast medium (ECM) and measurement of ECM washout
      halftime (t1/2) over opacified myocardial regions of interest, which displayed
      wall motion abnormalities already at rest.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7647023
TI  - Electrophysiologic effects of potassium channel openers.
AB  - Potassium-channel openers or activators have been introduced as a new class of
      antihypertensive and antianginal agents that act by increasing membrane
      conductance to potassium, mainly through augmentation of the ATP-sensitive
      potassium current. Recent in vitro studies have shown that K(+)-channel openers
      exert concentration-dependent effects on cardiac electrophysiology. A shortening
      of the cardiac action potential by acceleration of repolarization has been
      reported in multicellular preparations as well as in isolated myocytes. However,
      drug concentrations that affect the action potential duration of myocardial cells
      are considerably higher (10- to 100-fold) than those needed for effects on
      vascular smooth muscle cells. Studies in which mostly high concentrations of K(+)
      channel openers were used have demonstrated that these drugs may accelerate
      automaticity and may promote reentrant activity. Particular interest has focused
      on the question whether opening of potassium channels may be potentially
      arrhythmogenic in the setting of acute myocardial ischemia. On the other hand,
      recent studies have shown that K(+)-channel openers are effective in suppressing
      polymorphic ventricular tachyarrhythmias induced by early afterdepolarizations
      and triggered activity in vivo. The clinical relevance of these experimental
      studies to the clinical situation is still unclear. Some K(+)-channel openers
      have been shown to produce electrocardiographic T-wave changes in patients in
      whom their effectiveness as antihypertensives was tested. However, this effect
      was not associated with adverse effects and has not been demonstrated for all
      compounds.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7647025
TI  - Double-blind comparison of the acute effects of two relevant doses of oral
      nicorandil on central hemodynamics, left ventricular function, and myocardial
      contractility.
AB  - Nicorandil is a nicotinamide derivative with potent vasodilator properties. Oral
      and sublingual administration of this compound in patients with coronary artery
      disease resulted in a predominant reduction of afterload and a small decrease in
      left ventricular preload. The effects of nicorandil in different doses on
      contractile left ventricular (LV) function, however, are not well defined. The
      aim of the present study was to assess the effects of nicorandil on hemodynamics,
      left ventricular volume and function, as well as the LV contractility index dP/dt
      measured by Millar-tip manometers. A total of 16 patients with coronary artery
      disease were included in this study. After diagnostic coronary angiography and
      ventriculography, the patients randomly received either 10 or 20 mg of oral
      nicorandil. The hemodynamic parameters, cardiac output, and LV end-diastolic and
      systolic pressures were determined after 15, 30, and 60 minutes, and a second
      angiogram was performed 60 minutes after administration. The predominant effect
      was a decrease in the mean aortic pressure with a concomitant decrease in the
      peripheral arterial resistance. Clinically relevant changes in aortic pressure,
      systemic vascular resistance, and rate-pressure product, however, were documented
      only after oral administration of 20 mg nicorandil, as opposed to minimal changes
      in the 10 mg group. LV volume and cardiac output were not changed significantly.
      LV contractility remained unchanged during the observation period. The
      hemodynamic profile of this compound is dose-dependent afterload reduction
      without a change in contractility. Because there was no concomitant increase in
      heart rate, calculated oxygen consumption was reduced, especially in the higher
      dose group.

PMID- 7647027
TI  - Potassium channel openers: clinical applications in ischemic heart disease-
      overview of clinical efficacy of nicorandil.
AB  - Nicorandil is a balanced arterial and venodilator that may also possess
      cardioprotective properties via its activation of ATP-sensitive potassium
      channels. It has a number of beneficial hemodynamic effects and has been shown to
      be effective in treating angina with similar efficacy as the currently available
      antianginal agents. In addition, it may have useful effects in unstable and
      variant angina. In this review we examine the hemodynamic effects of nicorandil
      and discuss the currently available data on its clinical efficacy, both in
      isolation and in comparison with other agents.

PMID- 7647026
TI  - Management of vasospastic angina--role of nicorandil.
AB  - Clinical and experimental observations have confirmed that an episodic increase
      in the vasomotor tone of a major coronary artery may play a pathogenetic role not
      only in "variant angina" but also in other, more common anginal syndromes. In
      chronic stable angina, dynamic changes of vascular smooth muscle tone at the site
      of eccentric atheromatous plaques are responsible for "mixed angina." Abnormal
      coronary vasomotion contributes to myocardial ischemia in acute coronary
      syndromes as well. Studies have shown that a "primary" reduction of coronary
      blood flow, usually associated with plaque fissuring and thrombus formation,
      causes infarction and unstable angina. Abnormal vasoconstriction associated with
      the release of vasoactive substances by platelets and other constituents of the
      thrombus can contribute to coronary flow reduction in patients with unstable
      angina and myocardial infarction. Better understanding of the complex
      interactions among atherosclerotic coronary obstructions, the vascular smooth
      muscle, and the vascular endothelium has resulted in novel therapeutic approaches
      and has stimulated the search for more efficacious and safer coronary
      vasodilators. Recently interest has focused on vasodilator agents such as
      nicorandil that influence coronary arterial tone by acting through potassium
      channel activation. Nicorandil appears to be effective for treatment of
      vasospastic angina, as suggested by studies in Japan and Europe. In addition to
      its "antivasospastic" properties, nicorandil dilates coronary artery stenoses in
      patients with stable angina pectoris.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7647028
TI  - Nicorandil safety in the long-term treatment of coronary heart disease.
AB  - The results of an open prospective study that evaluated the long-term clinical
      safety of nicorandil are presented. This study included 199 patients with severe
      chronic stable angina treated over a 1-year period. The most often reported
      adverse event was headache, which was responsible for most of the study
      withdrawals due to clinical intolerance (9.6%). When using a progressive
      titration scheme, this incidence was substantially reduced to 2.7%. As with other
      less frequent adverse events (dizziness, gastrointestinal disorders), headaches
      were reported as being mild to moderate in severity, were experienced during the
      first days of treatment, and, if treatment was maintained, usually resolved
      within a few days. The incidence of adverse events was not modified when
      nicorandil was given in combination with a beta-blocker, a calcium antagonist, or
      both agents. Cardiovascular safety was satisfactory and laboratory parameters
      were not altered. At the end of the study, 70% of patients were maintained on
      nicorandil. These results are in agreement with those reported from the
      nicorandil safety database, which gathered 1152 patients treated by nicorandil,
      including those of the present study. In comparative studies of nicorandil versus
      beta-blockers, calcium antagonists, or nitrates, the overall incidence of adverse
      events was no different between the two treatment groups, although the safety
      profile differed according to the drug category.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7647029
TI  - Ischemic myocardial cell protection conferred by the opening of ATP-sensitive
      potassium channels.
AB  - The responses of the cardiac myocyte to a potentially injurious ischemic stress
      are multiple. The opening of the ATP-sensitive K+ channels may constitute one
      such response. These channels are present in the plasmalemma at very elevated
      density and have a large unitary conductance. Consequently, the opening of a
      small fraction (0.01-0.1%) of these channels during ischemia can help to drive
      the myocyte into an "emergency" state, in which its syncytial functions become
      rapidly downregulated and strategies appropriate to preserving cell viability are
      implemented. Thus, ATP-sensitive K+ channels in cardiac myocytes would appear to
      be an efficient and apparently redundant natural means of defense against
      metabolic stress. These channels can undergo physiologic modulation, as occurs
      during cardiac ischemic preconditioning in several species, including humans. The
      term cardioprotection refers to an endogenous cardioprotective strategy, whereby
      the myocardium slows its energy demands, produces fewer toxic glycolytic
      products, and exhibits reduced injury following a potentially lethal ischemic
      stress. Openers of cardiac ATP-sensitive K+ channels, a class of drugs that
      includes, in particular, aprikalim and nicorandil, also afford cardioprotection
      by reducing the functional and biochemical damage produced by ischemia. Hence,
      these compounds can improve the recovery of cardiac contractility, reduce the
      extracellular leakage of intracellular enzymes, delay the loss of ATP, and
      preserve the cell ultrastructure in isolated heart preparations subjected to
      transient ischemic conditions. Furthermore, when segmental contractility has been
      strongly depressed by a stunning insult, nicorandil and aprikalim can accelerate
      recovery at the reperfusion. Finally, nicorandil and aprikalim decrease
      substantially the size of the necrotic region that results from a prolonged
      ischemic insult followed by reperfusion. All of these desirable effects of K(+)
      channel openers can be abolished by blockers of ATP-sensitive K+ channels, such
      as glibenclamide. The fundamental mechanism of the myocyte viability protection
      conferred by K(+)-channel openers is not yet clear. It may exploit some of the
      same pathways that mediate cardiac ischemic preconditioning. If this suggestion
      holds true, drugs opening cardiac ATP-sensitive K+ channels would mimic, exploit,
      or intensify those cardioprotective means that are naturally available to the
      cardiac myocyte for overcoming metabolic stress.

PMID- 7647030
TI  - Antiischemic effects of nicorandil during coronary angioplasty in humans.
AB  - The present study was undertaken on 10 patients with angina undergoing
      percutaneous transluminal coronary angioplasty. The angioplasty procedure
      consisted of two successive 30-second balloon inflations at 5 minute intervals.
      After the first inflation, nicorandil (0.1 mg/kg) was given intravenously over a
      2-minute period. The second inflation was then performed 3 minutes after the
      completion of drug administration. Myocardial ischemia was measured as the
      magnitude of ST-segment elevation on the intracoronary electrocardiogram
      (intracoronary ECG) recorded from the guidewire. Nicorandil significantly reduced
      the magnitude of ST-segment elevation. Nicorandil did not change the heart rate
      blood pressure product, nor the oxygen saturation of the blood sampled from the
      great cardiac vein, nor the velocity of coronary blood flow in those patients
      with no evidence of collaterals. These results favor the conclusion that
      nicorandil prolongs the intrinsic ability of cardiac myocyte to withstand oxygen
      deprivation. This salutary effect is possibly due to a direct cellular mechanism
      because nicorandil did not modify the peripheral and coronary hemodynamic
      parameters that govern myocardial oxygen consumption.

PMID- 7647032
TI  - Combined vitamin D3/retinoic acid induction of human promyelocytic cell lines:
      enhanced phagocytic cell maturation and hybrid granulomonocytic phenotype.
AB  - Studies on the effect of retinoic acid (RA) and 1,25-dihydroxyvitamin (D3) on the
      differentiation of leukemic cells have provided insight into the cellular and
      molecular mechanisms underlying hematopoietic cell differentiation. We have
      evaluated the combined effect of these chemical inducers on the differentiation
      of HL-60 and AML-193 promyelocytic leukemia cell lines. Simultaneous RA+D3
      addition potentiated leukemic cell maturation up to mature phagocytic cells.
      Interestingly, AML-193 cells induced with D3 and RA displayed a typical
      neutrophilic morphology while exhibiting properties specific to monocytic cells,
      e.g., high expression of CD14 membrane antigen, capacity to bind bacterial
      lipopolysaccharide, and monocytic-specific esterase activity; this hybrid
      granulomonocytic (GM) phenotype was not observed upon initial incubation with one
      inducer and later addition of the other. Parallel control studies were performed
      with purified normal GM progenitors, triggered by interleukin 3+GM-colony
      stimulating factor (CSF) in FCS-rich or -free clonogenic culture, by GM-CSF+M-CSF
      in FCS-rich clonogenic culture, and by M-CSF in liquid suspension culture. The
      progenitors grown in the first condition generate exclusively G clones, even upon
      addition of D3 and/or RA. The progenitors grown in the second and third culture
      conditions generate either G and M clones (second culture condition) or a
      population of cells composed by a majority of monocytes (third culture
      condition); the D3 addition did not modify this differentiation pattern, whereas
      RA or RA+D3 addition elicited a marked inhibition of monocytic differentiation.
      These observations suggest that the development of a hybrid GM phenotype is
      restricted to the progeny of bipotent GM leukemic precursors.

PMID- 7647031
TI  - Analysis of small cell lung cancer cell growth inhibition by 13-cis-retinoic
      acid: importance of bioavailability.
AB  - 13-cis-Retinoic acid can mediate differentiation of transformed cells and slow
      the proliferation of malignant cells, suggesting its use as a potential
      intervention tool. Specific cDNA probes for retinoic acid receptors demonstrated
      the expression of mRNAs for the different retinoic acid receptor isoforms in
      small cell lung cancer cell lines. Addition of 13-cis-retinoic acid to small cell
      lung cancer cells cultured using serum-free, hormonally defined medium resulted
      in a 5-8-fold increase in the level of the retinoic acid receptor-beta mRNAs; in
      medium containing serum, the increase in expression of the retinoic acid receptor
      beta mRNAs was less pronounced, usually no more than 2-fold. Using an in vitro
      proliferation assay, addition of 13-cis-retinoic acid resulted in a significant
      dose-dependent, growth-inhibitory effect on the small cell lung cancer cell lines
      tested using serum-free conditions. These inhibitory effects decreased when cells
      were cultured in medium containing serum or serum components. Molecular size
      exclusion chromatography and native gel electrophoresis showed that the causative
      serum component eluted and migrated with serum albumin. Preincubating serum with
      triglycerides restored the inhibitory effects of 13-cis-retinoic acid
      demonstrated in serum-free systems. These data suggest that 13-cis-retinoic acid
      preferentially binds to serum albumin, restricting its inhibitory effects on
      epithelial cell receptors. Blocking retinoic acid-albumin interactions with a
      fatty acid source may improve the bioavailability of 13-cis-retinoic acid and
      significantly enhance the inhibitory effect in vivo.

PMID- 7647033
TI  - Involvement of ornithine decarboxylase and polyamines in glucocorticoid-induced
      apoptosis of rat thymocytes.
AB  - Ornithine decarboxylase (ODC), the first and rate-limiting enzyme of polyamine
      metabolism, has been shown to be required for entry into and progression through
      the cell cycle. However, the role of ODC and polyamines in apoptosis remains to
      be determined. We have examined ODC expression and polyamine levels in thymocytes
      activated to undergo apoptosis by dexamethasone treatment. We have demonstrated a
      rapid and reversible induction of ODC (mRNA and activity), as previously reported
      for the mRNA expression of other "early" genes, c-fos, c-jun, and c-myc, in the
      same experimental model. Surprisingly, polyamine levels diminished progressively
      starting at 2-4 h after dexamethasone treatment, and spermine was depleted at 8
      12 h. This seemed to be relevant since increasing the intracellular polyamine
      levels by exogenous spermine administration prevented the DNA "laddering" (2-4 h)
      and the DNA loss from the nucleus (8-18 h) due to dexamethasone treatment.
      Moreover, the activities of spermidine/spermine N1-acetyltransferase, which
      controls the cytosolic polyamine interconversion pathway, and of spermidine N8
      acetyltransferase, which regulates the nuclear pool and functions of polyamines,
      were measured in apoptotic cells. Spermidine/spermine N1-acetyltransferase
      activity progressively increased and might be responsible for spermidine and
      spermine excretion as acetyl derivatives. In contrast, spermidine N8
      acetyltransferase activity remained unchanged. A completely different scenario
      was observed in proliferating concanavalin A-treated thymocytes, studied for
      comparison. In this case, polyamine levels increased, remaining at high values
      until 12 h. This is likely a consequence of the rapid and prolonged induction of
      ODC (mRNA and activity), accompanied by that of spermidine/spermine N1
      acetyltransferase (mRNA and activity).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7647034
TI  - Heterodimeric retinoic acid receptor-beta and retinoid X receptor-alpha complexes
      stimulate expression of the intercellular adhesion molecule-1 gene.
AB  - Human intercellular adhesion molecule-1 (ICAM-1), a specific ligand for the
      leukocyte-function associated antigen-1 and for Mac-1, plays an important role in
      immune responses. ICAM-1 expression is regulated by various proinflammatory
      cytokines, phorbol myristate acetate, and retinoic acid. In this study, we
      investigated the mechanisms of transcriptional control involved in the
      stimulation of ICAM-1 gene expression by retinoic acid in Cos-1 cells. Deletion
      mutant analysis provided evidence that a region located between -393 and -176
      from the translational start site is critical to retinoic acid stimulation of
      luciferase activity. This region harbors the consensus sequence for a retinoic
      acid-responsive element (RARE) 5'-GGGTCATCGCCCTGCCA-3'. The Smal(-270)/Smal (
      178) fragment containing this element conferred appropriate retinoic acid
      responsiveness to an enhancerless SV40 promoter. Cotransfection of expression
      vectors encoding the retinoic acid receptor alpha, beta, or gamma and retinoid X
      receptor alpha with reporter plasmids harboring the putative RARE demonstrated
      that the ICAM-1 gene is regulated by retinoic acid in a retinoic acid receptor
      beta/retinoid X receptor alpha-dependent fashion. Electrophoretic mobility shift
      assays showed that ICAM-1 and ADH3 RARE, a well-characterized RARE, display the
      same band shift pattern, bind retinoic acid receptor beta and retinoid X receptor
      alpha, and are mutually competitive.

PMID- 7647035
TI  - Transforming growth factor alpha regulation of two zinc finger-containing
      immediate early response genes in intestine.
AB  - The epithelium lining the intestine undergoes rapid and continuous renewal.
      Growth factors play a role in intestinal epithelial growth regulation in vitro
      and in vivo. In this study, transforming growth factor alpha (TGF alpha) is shown
      to act as a mitogen and induce the expression of two zinc finger-containing
      immediate early genes [Zif268 (zinc finger protein 268) and Nup475 (nuclear
      protein 475)] in rat intestinal epithelial (RIE-1) cells in culture. These two
      gene products were initially isolated from serum-treated fibroblasts and
      represent growth-stimulated transcription factors. In TGF alpha-treated RIE-1
      cells, nuclear run-on experiments demonstrate that TGF alpha induction of these
      two genes is regulated predominantly at the level of gene transcription.
      Utilizing in situ hybridization techniques, we show that systemic administration
      of TGF alpha induces expression of these two genes in the rat intestine. The
      predominant expression of zif268 is observed in the proliferative crypt
      compartment, whereas nup475 expression is concentrated in the postmitotic luminal
      compartment. These studies demonstrate that two immediate early genes, Nup475 and
      Zif268, are induced in intestinal epithelium in vitro and in vivo and thus may
      play a role in intestinal epithelial growth and/or differentiation.

PMID- 7647036
TI  - Adenovirus E1A antagonizes both negative and positive growth signals elicited by
      transforming growth factor beta 1.
AB  - Transforming growth factor beta 1 (TGF beta 1) is a cytokine capable of
      inhibiting or stimulating cell growth, depending on the nature of the target
      cell. Inhibition of cell growth by TGF beta 1 is thought to be mediated by TGF
      beta 1-induced changes in the expression and activity of cell cycle regulatory
      proteins like cyclin-dependent kinase (cdk) 2 and cdk4. Here we show that
      adenovirus E1A blocks growth inhibition by TGF beta 1. The activity of cdk2 was
      strongly inhibited by TGF beta 1 in control cells but not in E1A-expressing
      cells. Similarly, an early event in TGF beta 1 signaling, junB induction, was
      significantly reduced in E1A-expressing cells. E1A also interferes with growth
      stimulation of NRK cells by TGF beta 1, both in monolayer and in soft agar. In
      these cells, E1A also interferes with junB induction by TGF beta 1. Moreover, E1A
      abrogates TGF beta 1-induced production of an autocrine-acting platelet-derived
      growth factor-like activity. These results show that E1A can interfere with TGF
      beta 1-induced growth-inhibiting as well as growth-promoting signals.

PMID- 7647038
TI  - v-Raf activates transcription of growth-responsive promoters via GC-rich
      sequences that bind the transcription factor Sp1.
AB  - The serine/threonine kinase, Raf-1, is a component of intracellular signaling
      pathways that control responses to extracellular stimuli. Previously, we have
      shown that serum-induced transcription from the murine rep-3b and human mdr1
      promoters is Raf-dependent and that the activated Raf kinase, v-Raf, induces
      transcription of mdr1 via a GC-rich element. We now demonstrate that GC-rich
      sequences in the rep-3b promoter are both necessary and sufficient for induction
      by v-Raf. The GC-rich, v-Raf-responsive elements of rep-3b and mdr1 bind the
      general transcription factor Sp1 in electromobility shift assays. Mutation of a
      minimal GC-rich element abolished inducibility by v-Raf and eliminated binding by
      the transcription factor Sp1. However, Sp1 binding activity following serum
      stimulation of quiescent NIH 3T3 cells was unchanged, suggesting that mitogenic
      signals may stimulate the transactivation potential of prebound Sp1.

PMID- 7647037
TI  - The bidirectionally transcribed dihydrofolate reductase and rep-3a promoters are
      growth regulated by distinct mechanisms.
AB  - The mouse dihydrofolate reductase (dhfr) gene possesses a bidirectional promoter
      that produces functional transcripts in the opposite direction. These opposite
      strand transcripts encode the Rep-3 gene product, a protein that has homology to
      DNA mismatch repair enzymes. The core of the bidirectional promoter consists of
      four consensus binding sites for the transcription factor Sp1. These binding
      sites have been shown to be important for basal transcription from both the rep
      3a and dhfr promoters. Extensive characterization of the dhfr promoter has shown
      that growth-dependent regulation requires the E2F binding sites that flank the
      transcription initiation site. Here we show that endogenous rep-3a mRNA and the
      rep-3a promoter are growth regulated, in a manner very similar to the regulation
      of the dhfr mRNA and promoter region. However, we find that the E2F sites
      required for dhfr regulation are dispensible for regulation of the rep-3a
      promoter. Instead, we have shown that the rep-3a initiation region is critical
      for the G1S phase-specific activation of this promoter. Gel mobility shift
      experiments indicate that a member of the Sp1 family of transcription factors
      binds to the rep-3a initiation region, suggesting that this family of
      transcription factors may play a role in cell growth control.

PMID- 7647039
TI  - Transforming potential of the insulin receptor substrate 1.
AB  - The role of the insulin receptor substrate 1 (IRS-1) in cellular transformation
      was studied in R- cells, which are 3T3-like fibroblasts derived from mouse
      embryos with a targeted disruption of the insulin-like growth factor I receptor
      gene. These cells cannot be transformed by oncogenes that readily transform cells
      originating from wild-type littermate embryos (or other 3T3-like cells). In the
      present study, we demonstrate that in R- cells, the overexpression of the
      functional IRS-1 protein was sufficient to induce a mitogenic response to insulin
      but did not promote transformation, as measured by colony formation in soft agar.
      The coexpression of IRS-1 and the SV40 T antigen, however, induced
      transformation. Conversely, expression of an antisense IRS-1 RNA reversed the
      transformed phenotype in wild-type cells carrying the T antigen. Since the type 1
      insulin-like growth factor receptor, by itself, is fully transforming, we propose
      the hypothesis that the transforming competence of this receptor is based on at
      least two signaling pathways, one of which is IRS-1-dependent, whereas the
      other(s) can be substituted with the SV40 T antigen.

PMID- 7647040
TI  - Intracellular expression of the monoclonal anti-ras antibody Y13-259 blocks the
      transforming activity of ras oncogenes.
AB  - Microinjection of the anti-ras antibody Mab Y13-259 modifies ras function and can
      induce temporary reversion of the transformed phenotype in mutant ras-transformed
      cells. Intracellular production of neutralizing antibodies represents an approach
      to investigate the regulation of gene function. The genes coding for the heavy
      and light chains of Mab Y13-259 were isolated from a cDNA library. NIH3T3 cells
      transfected with heavy and light chain expression vectors produced functional
      anti-ras antibody. The production of functional antibody did not require
      glycosylation. To ensure that the antibody entered the cytoplasm and not the
      secretory pathway, the hydrophobic leader sequences of both chains were removed
      and replaced with synthetic initiator sequences. The modified heavy chain gene
      was cloned under the control of the murine sarcoma virus long terminal repeat,
      and the light chain gene under the control of the mouse mammary tumor virus long
      terminal repeat, which allows the induction of light chain expression in the
      presence of dexamethasone. When both heavy and light chain genes were expressed
      in cells with activated ras (morphologically transformed) in the presence of
      dexamethasone, we observed phenotypic reversion to characteristics of
      nontransformed cells. These experiments show that intracellular expression of
      antibodies can also be used as an alternative to analyze biological functions of
      a given protein.

PMID- 7647041
TI  - Calmodulin-dependent protein kinases in rat glioblastoma.
AB  - The mitogenic activity of several growth factors is mediated by calcium-dependent
      signal transduction. Calmodulin (CaM) binding proteins such as CaM-dependent
      protein kinases are important components of this pathway and may be altered in
      diseases characterized by abnormal cell growth. CaM kinase II is believed to
      regulate the phosphorylation of microtubular-associated proteins and control the
      initiation of DNA synthesis. Furthermore, drugs that inhibit CaM-mediated signal
      transduction also inhibit cellular proliferation and are cytotoxic to numerous
      malignant cell lines, including those established from malignant gliomas. Yet,
      little is known about CaM-dependent protein kinases in these tumors. Therefore,
      we have investigated the activity and distribution of CaM-dependent protein
      kinase II in normal and malignant glial tissues, a kinase believed to play a
      critical role in cell cycle regulation. C6 and 9L cells contained kinase
      activities that were activated by Ca2+/CaM and inhibited by trifluoperazine.
      Tissue extracts from these cell lines and from rat brain white matter
      phosphorylated exogenous synapsin I in a pattern consistent with the presence of
      CaM kinase II activity as determined by phosphopeptide mapping. CaM kinase II
      activity was confirmed using a specific peptide substrate and inhibitor. An
      unexpected finding was that glioma lines, but not rat brain white matter, also
      contained a CaM-dependent protein kinase detected by the phosphorylation of a
      M(r) 100,000 protein, subsequently identified as elongation factor 2, the only
      known substrate for CaM kinase III.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7647042
TI  - Violence against women of color. Introduction.

PMID- 7647044
TI  - Child sexual abuse and adult revictimization with women of color.
AB  - Clinical researchers examining the long-term consequences of child molestation
      have reported that female survivors of child sexual abuse experience a higher
      risk of sexual assaults as adults. However, very little literature has focused on
      the child and/or adult sexual victimization of women from different ethnic or
      cultural backgrounds. In examining the long-term consequences of child sexual
      abuse, this investigation examined the rates of sexual revictimization of women
      of color. A multiethnic (white, African-American, Latina, and Asian-American)
      sample of 243 women, recruited and randomly selected from a pool of volunteers
      from two community colleges, were administered extensive clinical interviews.
      Nearly two thirds of the women who reported rape as an adult had a history of
      child sexual abuse while approximately one third of the non-victimized women had
      a child sexual abuse history. Additionally, an examination of the rates of adult
      rape within each ethnic group revealed differences between the women with and
      without a history of child sexual abuse. Significant differences (i.e., higher
      rates of rape associated with a prior history of child sexual abuse) were found
      for white women, African-American women, and Latinas, but not for Asian-American
      women. The results of this investigation highlight the relationship between child
      sexual abuse and adult rape and suggest the need for researchers to take a
      broader cultural context in which to view sexual victimization.

PMID- 7647043
TI  - Sociocultural status and incidence of marital violence in Hispanic families.
AB  - It is not clear whether traditional cultural ideology influences wife assaults in
      Hispanic-American families, or if culture is confounded with the stresses of
      poverty, unemployment, and immigration status. Our 1992 study of 1,970 families,
      including a national oversample of Hispanic families, examines the incidence of
      marital violence in the three major Hispanic-American subgroups and in Anglo
      American families, and considers how sociocultural status and attitudes towards
      violence affect wife assaults differentially. The findings show that Hispanic
      Americans, as a whole, do not differ significantly from Anglo Americans in their
      odds of wife assaults when norms regarding violence approval, age, and economic
      stressors are held constant. At the same time, considerable heterogeneity was
      apparent among ethnic subgroups on a number of measures. We also found that being
      born in the United States increases the risk of wife assaults by Mexican- and
      Puerto Rican- American husbands. However, the presence of norms sanctioning wife
      assaults within any group, regardless of socioeconomic status, is a risk factor
      for wife abuse.

PMID- 7647045
TI  - Sexual harassment and prior sexual trauma among African-American and white
      American women.
AB  - This study examined the relationship between sexual harassment in work,
      educational, and social settings and sexual abuse in childhood and/or adulthood
      in a stratified community sample of 248 African-American and white American
      women. The cumulative impact of sexual victimization on women's sense of general
      well-being was also examined. Those most likely to be sexually harassed in work
      and social settings were women with contact sexual abuse histories, regardless of
      ethnicity. The work status of harassers of women with sexual abuse histories
      differed significantly by ethnic group. Although women with prior sexual abuse
      experiences from both ethnic groups most frequently reported a response to sexual
      harassment at work, they least frequently did so in social settings. A history of
      childhood sexual abuse was more negatively associated with African- American
      women's well-being than were repeated experiences of sexual violence. Future
      research should address the implications of ethnic and cultural issues on the
      cumulative impact of incidents of sexual violence on women of color.

PMID- 7647046
TI  - Grandmother dishonored: violence against women by male partners in American
      Indian communities.
AB  - Extensive and scrupulously conducted research during the past decade has
      established the issue of violence against women by male partners as both an
      international human rights issue and a public health problem of national concern.
      This research has rarely been extended into communities of color, and, in
      particular, to American Indian women. This article presents conceptual and
      methodological factors involved in conducting research with American Indian
      women, a comprehensive literature review of available data, assertions regarding
      abuse of women by male partners in American Indian communities, and directions
      for future research.

PMID- 7647048
TI  - Adjustment and needs of African-American women who utilized a domestic violence
      shelter.
AB  - To better understand what environmental and contextual factors influence resource
      acquisition and subsequent adjustment for African-American women who have been
      battered, this article explores the experiences of 60 women from the 6 months
      prior to entering a shelter through a 10-week postshelter advocacy program.
      Results indicate that African-American battered women who use domestic violence
      shelters face an array of obstacles: Most had been severely abused were likely to
      be living below the poverty line, were unemployed, and were in need of numerous
      resources. However, in spite of numerous obstacles and continued violence,
      African-American women overall felt confident in themselves and satisfied with
      their lives 10 weeks after shelter. Results also indicate that short-term
      advocacy services were beneficial to African-American women exiting a domestic
      violence shelter. Implications of these findings as they relate to formal
      community response and further research are discussed.

PMID- 7647047
TI  - The reliability and factor structure of the index of spouse abuse with African
      American women.
AB  - This study investigated the reliability and validity of the Index of Spouse Abuse
      (ISA) when used with a sample of 504 African-American women. The initial factor
      validity analysis for the ISA (Hudson & McIntosh, 1981) resulted in two
      subscales: a physical abuse scale (ISA-P) and a nonphysical abuse scale (ISA-NP).
      Factor analysis with this sample of African-American women revealed three factors
      instead of two. Coefficient alpha estimates of reliability were over .90 for the
      original ISA subscales and with the African-American sample. The discussion
      compares and contrasts the factor structure observed with the sample of African
      American with the factor structure reported in the original validation studies.
      The study demonstrates the need to critically evaluate the extent to which
      instruments developed to measure spouse or partner abuse are valid and reliable
      when used with diverse groups that may not have been represented in the samples
      used for initial instrument development and validation work.

PMID- 7647049
TI  - Domestic partner abuse treatment programs and cultural competence: the results of
      a national survey.
AB  - Partner abuse literature reveals that treatment is less effective with minorities
      than with their white counterparts. Our survey of partner abuse programs (N =
      142) indicates that, for the most part, little or no special effort is being made
      to understand or accommodate the needs of minority populations. This colorblind
      approach lacks the effectiveness of a culturally competent approach, which
      fosters an environment that helps minority groups succeed in treatment. Do
      partner abuse programs make efforts to be culturally competent? The major
      characteristics of an organizational transformation towards cultural competence
      occur when these programs do the following: (a) network with the minority
      community, (b) locate outside consultants with expertise in working with minority
      clients, (c) obtain information concerning service delivery and programming for
      minority clients, and (d) have at least one bilingual counselor. These four
      characteristics accounted for .58 of the variance in the minority-focused
      activities.

PMID- 7647050
TI  - Is cervical cytology screening of teenagers worthwhile?

PMID- 7647051
TI  - Dealing with the report of a mild dyskaryotic smear.

PMID- 7647054
TI  - Fatty acid pattern of esterified and free fatty acids in sera of women with
      normal and pre-eclamptic pregnancy.
AB  - OBJECTIVE: To determine the composition of esterified and free fatty acids in
      sera of women with normal and pre-eclamptic pregnancy. SETTING: Department of
      Obstetrics and Gynaecology, Aker Hospital, Oslo, Norway. SUBJECTS: Blood samples
      were taken from 510 healthy nulliparae at a gestational age of 17-19 weeks.
      Nineteen of these subsequently developed pre-eclampsia. Seventeen of these, for
      whom blood samples were still available, and a control group of 17 women taken
      from the same population and matched for age, body mass index, gestational age
      and parity, were later studied in detail. A further group of 29 women admitted to
      the hospital with pre-eclampsia were also studied, as was a matched control group
      of 29 women with normal pregnancies recruited from the antenatal clinic. METHODS:
      Blood samples were drawn after 8 to 10 h fasting. The patterns of serum free
      fatty acids and esterified fatty acids were determined by thin-layer
      chromatography combined with gas-liquid chromatography. Free fatty acids were
      also determined enzymatically. RESULTS: Among the circulating free fatty acids,
      the levels of palmitic (16:0), oleic (18:1 n-9) and linoleic acids (18:2 n-6)
      were significantly higher early in pregnancy in women who later developed pre
      eclampsia. The same free fatty acids were also significantly increased in women
      with pre-eclampsia. The level and composition of the esterified fatty acids in
      phospholipids, triglycerides and cholesteryl esters did not, however, differ
      between the two groups early in pregnancy. In contrast, in women with pre
      eclampsia, the relative content of oleic acid was increased in the phospholipid
      fraction, whereas linoleic acid was decreased in the phospholipid and
      triglyceride fractions. CONCLUSIONS: We observed that the level and composition
      of circulating free fatty acids were already altered 10-20 weeks before the
      clinical onset of pre-eclampsia. When the disease became overt there were changes
      in both esterified and free fatty acids.

PMID- 7647052
TI  - Complications of pregnancy after infertility treatment: awareness and prevention.

PMID- 7647053
TI  - Single pre-delivery symphysis-fundal height measurement as a predictor of
      birthweight and multiple pregnancy.
AB  - OBJECTIVE: To compare the value of different pre-delivery maternal indices for
      predicting birthweight, and to examine the usefulness of a single pre-delivery
      symphysis-fundal height measurement for the detection of low birthweight and twin
      pregnancy or macrosomia. DESIGN: Symphysis-fundal height measurements were
      gathered from 1509 women who had both a singleton delivery and available data of
      pre-delivery weight, height and mid-upper arm circumference, and from 73 women
      who had a twin delivery. SETTING: A district hospital in rural Tanzania. RESULTS:
      Symphysis-fundal height, pre-delivery weight and mid-upper arm circumference,
      respectively, explain 41%, 13% and 4% of the observed variation in birthweight.
      At a cut-off level of 30 cm for symphysis-fundal height, the detection rate for
      birthweight below 2500 g and 2000 g was 66% and 68%, respectively, and the false
      positive rate was 9% and 14%, respectively. At a cut-off level of 38 cm for
      symphysis-fundal height the detection rate for twin pregnancy or birthweight > or
      = 4000 g was 76%, and the false positive rate was 4%. CONCLUSION: Symphysis
      fundal height was a better predictor of birthweight than maternal height, pre
      delivery weight or mid-upper arm circumference. It seems justified to investigate
      the value of a simple tricoloured symphysis-fundal height measuring tape for use
      in antenatal care in developing countries at village level.

PMID- 7647056
TI  - Does colposcopically directed punch biopsy reduce the incidence of negative
      LLETZ?
AB  - OBJECTIVE: To evaluate the role of punch biopsy in reducing the occurrence of
      negative histology provided by large loop excision of the transformation zone in
      the management of cervical intraepithelial neoplasia. DESIGN: Retrospective
      review of computerised data base and clinic files. SETTING: Colposcopy Clinic,
      Groote Schuur Hospital, Cape Town, South Africa. SUBJECTS: Two hundred and ninety
      eight women considered suitable for the local outpatient management of cervical
      intraepithelial neoplasia. METHODS: Two groups of patients were identified: group
      A consisted of women who had cervical intraepithelial neoplasia confirmed
      colposcopically and who underwent directed punch biopsy; group B consisted of
      women who had cervical intraepithelial neoplasia confirmed colposcopically and
      were referred for large loop excision of the transformation zone without
      confirmatory punch biopsy. RESULTS: In Group A (n = 184) 123 women had cervical
      intraepithelial neoplasia diagnosed on punch biopsy. Large loop excision of the
      transformation zone was performed on 116 women and 7 were lost to follow up. The
      procedure confirmed cervical intraepithelial neoplasia in 95 cases (82%), but
      there was no cervical intraepithelial neoplasia in 21 cases (18%). Sixty-one
      women had negative punch biopsies. Of these, 13 underwent large loop excision of
      the transformation zone, 31 had persistently negative follow up cytology, and 9
      had positive cervical smears of which 7 were treated with large loop excision of
      the transformation zone, and 8 were lost to follow up. Overall, 25% of all
      negative punch biopsies were falsely negative. In group B 114 were treated with
      large loop excision of the transformation zone and cervical intraepithelial
      neoplasia was confirmed in 97 cases (85%); one woman had unsuspected
      microinvasion (1%) and 16 women (14%) had no cervical intraepithelial neoplasia.
      Negative histology after large loop excision of the transformation zone was not
      statistically different in groups A and B. CONCLUSION: Punch biopsy does not
      reduce the occurrence of negative histology after large loop excision of the
      transformation zone.

PMID- 7647055
TI  - Incidence of cervical smears indicating dysplasia among Austrian women during the
      1980s.
AB  - OBJECTIVE: To determine the incidence of cervical smears indicating cervical
      intraepithelial neoplasia during the 1980s and to compare two quinquennia.
      DESIGN: A retrospective epidemiologic analysis was performed, based on a large
      collection of 238,261 cervical smears obtained from Austrian women screened
      between 1980 and 1989. After application of strict epidemiologic criteria to
      avoid bias of changes in socio-economic status and methodological changes in
      cytology, 12,604 women were eligible for further analysis. We calculated
      incidences and relative risks of cytologically indicated cervical intraepithelial
      neoplasia, comparing the time periods of 1980 to 1984 and 1985 to 1989 for
      different age cohorts. RESULTS: We found a statistically significant increase in
      the incidence of cervical cytology indicating cervical intraepithelial neoplasia
      in the second time period for patients between 21 and 40 years of age. Women
      older than 40 years showed a significant decrease of this incidence. CONCLUSIONS:
      In Austrian women between the ages of 21 and 40 years an unidentified risk factor
      or a pattern of risk factors during the period prior to 1985 resulted in an
      increase of cervical intraepithelial neoplasia during the last years studied.
      This increasing incidence of cervical intraepithelial neoplasia indicates the
      importance of regular cytological screening. The significant decrease of the
      cervical intraepithelial neoplasia incidence in women older than 40 years
      provides an argument for increasing screening intervals in these women.

PMID- 7647057
TI  - The 1993 British Society for Colposcopy and Cervical Pathology/National
      Coordinating Network United Kingdom Colposcopy Survey. Comparison with 1988 and
      the response to introduction of guidelines.
AB  - OBJECTIVE: To evaluate colposcopic practice over a 12-month period in the UK,
      April 1993 to March 1994, to compare this with 1988, and to test penetration and
      acceptance of previously introduced national guidelines. DESIGN: A nationwide
      survey of colposcopy practice by postal questionnaire, including referral
      criteria, diagnosis and treatment, follow up, waiting times and information and
      counselling. SETTING: All gynaecology clinics in the United Kingdom. RESULTS:
      Returns were obtained from 215 clinics (78%), that saw an average of 434 new
      women per year. Seventy percent of clinics follow the current national guideline
      for cytological referral criteria for colposcopy. Diathermy loop excision is now
      by far the most popular treatment method for CIN. The majority of clinics employ
      both colposcopy and cytology for follow up. A total of 103 invasive cancers
      following treatment for CIN were reported during the 12-month period of the
      survey. Most clinics provide new patients with both information and counselling.
      CONCLUSIONS: Colposcopy practice has undergone considerable changes in the last
      five years. There has been a good response to the introduction of a national
      guideline for referral for colposcopy. While local audits are necessary to
      identify improvements that need to be made to individual clinical services, this
      national audit has shown some trends over the past five years, has highlighted
      the problem of invasive cancer following treatment for CIN and has assessed the
      impact of a national guideline.

PMID- 7647059
TI  - Mid-trimester termination for fetal abnormality: advantages of a new regimen
      using mifepristone and misoprostol.

PMID- 7647058
TI  - Effects of gemeprost and mifepristone on the mechanical properties of the cervix
      prior to first trimester termination of pregnancy.
AB  - OBJECTIVE: To study the effects of oral mifepristone and vaginal gemeprost on the
      mechanical properties of the cervix prior to first trimester termination of
      pregnancy by vacuum aspiration. DESIGN: A comparative study. Each patient served
      as her own control. SETTING: The Royal Infirmary of Edinburgh, Scotland, UK.
      SUBJECTS: Forty nulliparous women at six to twelve weeks of pregnancy.
      INTERVENTIONS: The women received either gemeprost (1 mg) 3 h prior to
      termination of pregnancy or mifepristone (200 mg) 48 h before operation. MAIN
      OUTCOME MEASURES: Two different objective methods of assessment of the mechanical
      properties of the cervix, one measuring the distensibility of the cervix before
      drug administration and immediately before the operation, and the other measuring
      the force necessary to dilate the cervix; incidence of new symptoms following
      drug intake; immediate complications and estimated blood loss. RESULTS: Both
      treatments significantly increased cervical distensibility. Baseline dilatation
      was greater in the mifepristone group. The force required to dilate the cervix
      was significantly reduced in mifepristone-treated patients. There was a good
      correlation between the two different methods of assessment of the mechanical
      properties of the cervix only in the gemeprost group. CONCLUSION: Cervagem and
      mifepristone can be used to increase cervical distensibility. Cervical dilatation
      is easier with a 48 h regimen of mifepristone than with gemeprost.

PMID- 7647061
TI  - Anonymous testing for drug abuse in an antenatal population.

PMID- 7647060
TI  - Fetal and maternal hCG concentration in aneuploid pregnancies.

PMID- 7647062
TI  - A laparoscopic procedure for the treatment of vaginal aplasia.

PMID- 7647063
TI  - Chemotherapy changes the DNA ploidy in ovarian cancer.

PMID- 7647065
TI  - Cancer associated human papillomaviruses: perinatal transmission and persistence.

PMID- 7647064
TI  - Interpretation of cyclosporin A levels in pregnancy following orthoptic liver
      transplantation.

PMID- 7647066
TI  - Oophorectomy at the same time as hysterectomy.

PMID- 7647067
TI  - Oophorectomy at the same time as hysterectomy.

PMID- 7647068
TI  - Human papillomavirus vulvitis: a new disease or an unfortunate mistake?

PMID- 7647069
TI  - Hydralazine boluses for the treatment of severe hypertension in pre-eclampsia.

PMID- 7647070
TI  - The management of severe ovarian hyperstimulation syndrome.

PMID- 7647071
TI  - Repair of rectovaginal fistula with traction in a HIV positive patient.

PMID- 7647073
TI  - Chaos theory in obstetrics and gynaecology.

PMID- 7647072
TI  - Conserving the cervix at hysterectomy.

PMID- 7647074
TI  - Chaos theory in obstetrics and gynaecology.

PMID- 7647075
TI  - A population-based, controlled study of the relation between HIV infection and
      cervical dysplasia.

PMID- 7647076
TI  - Low dose combined oral contraceptives.

PMID- 7647077
TI  - A randomised controlled trial of prophylaxis of post-abortal infection:
      ceftriaxone versus placebo.

PMID- 7647078
TI  - Developments in psychoneuroendocrinology: a tribute to the research of Robert A
      Cleghorn, 1904-1995.

PMID- 7647079
TI  - A comparison of placebo responders and nonresponders in subgroups of depressive
      disorder.
AB  - The objective of this study was to determine if the placebo treatment response
      varied in subgroups of depressed patients (single episode, recurrent, and double
      depression). Data from placebo-treated patients from seven placebo-controlled
      clinical trials were pooled and analyzed retrospectively. The placebo response
      rate was highest for females with a single episode of depression (66.7%) and
      lowest for females with recurrent depressive episodes (13.3%). Among patients
      experiencing their first episode, placebo responders had lower Hamilton Rating
      Scale for Depression (HAMD) total scores at baseline and lower ratings of
      pschomotor retardation than nonresponders. For patients having a recurrence of an
      episode, placebo responders had lower baseline ratings of somatic anxiety. The
      major finding was that patients suffering from their first depressive episode
      differed from patients with recurrent depressive episodes in the rate of placebo
      response, effect of gender, and the clinical symptoms that were associated with a
      positive placebo response.

PMID- 7647081
TI  - Olfactory identification ability in anorexia nervosa.
AB  - OBJECTIVE: The hypothesis tested was that patients with severe eating disorders
      would demonstrate olfactory identification deficits as a result of zinc
      deficiency or malnutrition. METHOD: The University of Pennsylvania Smell
      Identification Test (UPSIT) was administered to 27 hospitalized female patients
      with anorexia nervosa and 50 normal control female subjects. For a subgroup of
      patients, serum zinc levels and body mass indices were obtained at pre- and post
      nutritional repletion phases. RESULTS: UPSIT scores for patients with eating
      disorders were equivalent to normal control subjects in spite of the fact that
      the patients were nutritionally compromised as determined by body mass index.
      Serum zinc levels were not significantly different at pre- and post-nutritional
      repletion. CONCLUSIONS: In contrast to patients with schizophrenia, patients with
      severe eating disorders have intact olfactory function. This finding suggests
      that transient metabolic or nutritional disturbances alone cannot account for
      previously reported olfactory deficits.

PMID- 7647080
TI  - Clinico-pathological correlation in dementias.
AB  - The object of this study is to investigate whether or not there are clinical
      signs and symptoms in patients with dementia that, by themselves or jointly, can
      be associated with the pathological diagnosis of Alzheimer's disease. Twelve
      patients with dementia were studied, in whom the clinical diagnosis of
      Alzheimer's disease was made according to established criteria. A sample of
      leptomeninges, cortex and subcortical white matter was obtained from each patient
      and was processed for light and electron microscopy. In the cases in whom
      neuritic plaques and neurofibrilary tangles were present, pathological changes
      were quantified. The diagnosis of Alzheimer's disease was confirmed in 5 cases,
      whereas in 3 patients spongiform encephalopathy was present. In the remaining
      patients, the number of neuritic plaques was within normal limits for the age of
      the subjects. Comparison of the data in Alzheimer (n = 5) and non-Alzheimer (n =
      7) groups showed an increased, statistically significant incidence of acalculia,
      abnormalities of judgment, impairment of abstraction and primitive reflexes in
      the former. Although good fitting models were obtained, none achieved perfect
      discrimination. The model that included alterations of judgment and acalculia
      gave the best fit.

PMID- 7647082
TI  - An open study of tolerability and pharmacokinetics of raclopride extended release
      capsules in psychiatric patients: a Canadian study.
AB  - The tolerability and pharmacokinetics of raclopride extended release (ER)
      capsules have been evaluated after a single oral dose and at steady state, with 3
      different daily doses in 4 male patients requiring neuroleptic treatment. In this
      3-week open study, the drug was administered to patients in increasing bid doses
      of 8 mg, 12 mg and 16 mg, respectively, for each 1-week treatment period,
      following a 1-week placebo washout. With this limited number of patients,
      assessments of clinical chemistry, hematology, cardiovascular variables and
      adverse symptoms suggest that raclopride is safe and well-tolerated in the group
      studied. The administration of repeated doses of raclopride showed linear
      pharmacokinetics based on parameter values which are either constant (effective
      elimination half-life, total plasma clearance, and dose-normalized area under the
      plasma concentration-time curve) or varying proportionally (trough plasma
      concentration, peak plasma concentration, average plasma concentration and the
      area under the plasma concentration-time curve for a dosage interval at steady
      state) with the doses. The linear 1-compartment open model with zero-order
      absorption was the most appropriate pharmacokinetic model describing the
      raclopride plasma concentration profile after a single 8 mg dose of raclopride ER
      capsules. The ER formulation reduced the fluctuation between peak and trough
      plasma drug concentrations which has been reported before with instant release
      dosage forms. In this study, the increase of plasma prolactin concentrations
      above the normal limit was transient and returned to normal levels. Although the
      plasma prolactin concentration tended to increase with the drug dose, no direct
      relationship between raclopride dose and prolactin plasma concentrations was
      found. The correlation of plasma prolactin response with the plasma raclopride
      concentration showed a low level of hysteresis.

PMID- 7647084
TI  - Neuroleptic malignant syndrome and lithium carbonate.
AB  - The authors describe a case of neuroleptic malignant syndrome that occurred in a
      patient on amitriptyline and lithium carbonate. They suggest that lithium
      antidepressant combination can precipitate this syndrome. Intestinal pseudo
      obstruction was a prominent feature in the patient in this study.

PMID- 7647083
TI  - Melatonin responses to clonidine and yohimbine challenges.
AB  - Melatonin (MT) release from the pineal gland has been used as a marker for
      central noradrenergic function in major depression. Norepinephrine acts at both
      alpha and beta adrenergic receptors on the pinealocyte membrane to mediate
      nocturnal MT release, but in humans the contribution of each receptor class is
      unclear. In order to explore the effect of alpha 2 receptors on MT release, 10
      female subjects were given oral challenges, in separate placebo-controlled
      trials, of either 10.8 mg of yohimbine, an alpha 2 adrenergic antagonist, or
      clonidine, a partial alpha 2 adrenergic agonist, at doses of either 200
      micrograms or 300 micrograms. Post-challenge serum melatonin was measured from
      18:00 h to 22:00 h in both studies as was urinary 6-sulphatoxy-melatonin (aMT6s),
      the major metabolite of MT (from 18:00 h to 22:00 h, and from 22:00 h to 10:00
      h). Growth hormone (GH) was also assayed following the clonidine challenge, and
      blood pressure, pulse rate, and side effects were monitored after both
      challenges. Neither yohimbine nor clonidine significantly altered nocturnal serum
      MT levels compared to placebo. However, there was a significant increase in
      urinary aMT6s between 18:00 h and 22:00 h following yohimbine ingestion.
      Yohimbine ingestion produced significant rises in pulse rate and the urge to
      urinate compared to placebo. Both doses of clonidine resulted in a significant
      reduction in pulse rate, systolic and diastolic blood pressure, and significant
      increases in drowsiness and other measures of sedation following ingestion. Only
      clonidine 300 micrograms produced a significant elevation in GH release. This
      study highlights the limitations of oral neuroendocrine challenge studies.

PMID- 7647085
TI  - Psychosis in Apert's syndrome with partial agenesis of the corpus callosum.
AB  - A 19-year-old male with Apert's syndrome developed psychotic symptoms that
      responded to haloperidol. He was also found to have partial agenesis of the
      corpus callosum and enlarged lateral ventricles on a head CT scan. The
      implications of these findings in the context of psychotic symptoms are
      discussed. There are no previous reports of psychosis in patients with Apert's
      syndrome.

PMID- 7647086
TI  - Cloning, expression and structure of catechol-O-methyltransferase.

PMID- 7647087
TI  - Catalytic properties of rabbit serum esterases hydrolyzing esterified
      monosaccharides.
AB  - Rabbit serum and one enzyme fraction isolated from rabbit serum by column
      chromatography (Fraction II) were used as catalysts in regioselective hydrolysis
      of radiolabelled pivaloylated monosaccharides (Piv = Me3CCO). The hydrolysis of
      14C-labelled methyl 2-O-pivaloyl-(2-MP)-, 6-O-pivaloyl (6-MP)-, 2,6-di-O-pivaloyl
      (2,6-DP) alpha-D- glucopyranosides and methyl 2-acetamido-2-deoxy-3,6- di-O
      pivaloyl-(3,6-DPNAc) alpha-D-glucopyranosides, was studied, as well as that of
      the non-sugar substrates butyrylthiocholine, thiophenylbutyrate, phenylacetate
      and paraoxon. The specific activities of 2,6-DP, 3,6-DPNAc, butyrylthiocholine
      and thiophenylbutyrate were higher in Fraction II than in native sera, while
      those of phenylacetate and paraoxon were lower. Inhibition studies were done
      using the substrates mentioned and five different inhibitors, namely bis(p
      nitrophenyl phosphate) (BNPP), eserine, paraoxon, HgCl2 and EDTA. The hydrolysis
      of 2,6-DP and 3,6-DPNAc was not inhibited by HgCl2 and only slightly by EDTA.
      Paraoxon, eserine and BNPP were progressive inhibitors of the hydrolysis of the
      two sugar substrates, and the pattern of inhibition resembled closely the
      inhibition of butyrylthiocholine and thiophenylbutyrate hydrolysis. This result
      applied to both, native serum and Fraction II. It was concluded that esterases in
      rabbit serum which hydrolyze pivaloylated sugar substrates belong to the category
      of serine esterases. Kinetic parameters (KM and Vmax), effects of temperature and
      pH on activity of esterases from Fraction II were also determined for the
      hydrolysis of sugar substrates.

PMID- 7647088
TI  - Reaction of ferric leghemoglobin with H2O2: formation of heme-protein cross-links
      and dimeric species.
AB  - Ferric leghemoglobin in the presence of H2O2 is known to give rise to protein
      radicals, at least one of which is centred on a tyrosine residue. These radicals
      are quenched by at least two processes. The first one involves an intramolecular
      heme-protein cross-link probably involving the tyrosine radical; this leads to
      the formation of a green compound with spectral characteristics differing
      markedly from those of ferryl and ferric leghemoglobin. This green compound
      cannot be reduced by dithionite or ascorbate, precluding any role for this
      species as an oxygen carrier. It exhibits modified EPR and pyridine
      haemochromogen spectra, indicating that alterations occur at the porphyrin
      macrocycle level. The additional compound previously described [Puppo, A., Monny,
      C. and Davies, M.J. (1993) Biochem. J. 289, 435-438] appears to be a mixture of
      ferry Lb and this green compound. The second quenching route results in the
      formation of intermolecular cross-links and hence dimeric forms of the protein.
      Ascorbate and glutathione inhibit both this intermolecular dimer formation and
      the formation of the intramolecular haem-protein cross-links and are likely to
      play a protective role in vivo.

PMID- 7647089
TI  - Preparation by site-directed mutagenesis and characterization of the E211Q mutant
      of yeast enolase 1.
AB  - The published 'charge shuttle' mechanism of enolase (Lebioda, L. and Stec, B.
      (1991) Biochemistry 30, 2817-2822) assigns Glu-211 the task of orienting a water
      molecule that serves as the catalytic base which removes the proton from carbon-2
      of the substrate. We prepared the E211Q mutant of yeast enolase 1 by site
      directed mutagenesis. It appears to be folded correctly and to respond similarly
      to many of the normal ligands of enolase: it is stabilized against thermal
      denaturation by conformational Mg2+ and by Mg2+ and substrate and binds the
      chromophoric substrate analogue D-tartronate semialdehyde-2-phosphate (TSP) with
      affinity comparable to that of the native enzyme. However, it has only 0.01% (10(
      4)) of the activity of native enolase under standard assay conditions and does
      not exhibit significantly more activity at various pH values or higher
      concentrations of substrate and Mg2+. Its ability to produce the form of enzyme
      bound and reacted TSP that absorbs at shorter wavelengths is greatly slowed,
      while the longer wavelength absorbing form is produced rapidly. Overall, these
      observations are consistent with the hypothetical mechanism.

PMID- 7647090
TI  - Polyketide synthase acyl carrier proteins from Streptomyces: expression in
      Escherichia coli, purification and partial characterisation.
AB  - Acyl carrier proteins (ACPs) of the type II polyketide synthases for the aromatic
      antibiotics actinorhodin, granaticin, frenolicin and oxytetracycline were
      expressed in Escherichia coli downstream of an inducible phage T7 promoter. For
      the act and otc genes, several of the first eight codons were changed to
      synonymous codons used in highly expressed E. coli genes. Correlated with these
      changes, the amounts of the act and otc ACPs purified from the recombinant E.
      coli cultures were an order of magnitude greater than for the gra and fren ACPs
      expressed from the unmodified genes. Electrospray mass spectrometry (ESMS) of the
      purified proteins confirmed their calculated M(r) based on the DNA sequences
      while also revealing that, in the act and gra ACP samples, some 2% and 30% of the
      holo-form of the protein was present (i.e., carrying the 4'-phosphopantetheine
      prosthetic group), with the remainder (and 100% of the otc and fren samples)
      being in the apo-form. Increasing incubation time post heat induction led to an
      increase in act holo-ACP. The recombinant act and gra ACPs could function in
      vitro as substrates for an S. coelicolor malonyl CoA:ACP acyl transferase, as
      measured by the coupling of a labelled malonyl unit to the ACP; their
      quantitative abilities to do so correlated with the proportions of deduced holo
      form in the two samples.

PMID- 7647091
TI  - Decorating actin filaments with troponin T-I complexes and acceleration of their
      sliding movement on myosin molecules.
AB  - Actin filaments, when partially decorated with troponin T-I complexes, can slide
      faster on myosin heads than those with no decoration. Purified troponin T-I
      complexes bind to actins, and inhibit the actin activated myosin adenosine 5'
      triphosphatase activity completely when the molar ratio of troponin T-I complex
      to actin is increased to 1 to 1. Those actin filaments decorated with troponin T
      I complexes up to 20 to 50% of their molar ratio exhibit enhancement of the
      velocity of sliding on myosins up to 20% compared to those without such
      decoration. As the molar ratio of decoration further increases, the sliding
      velocity decreases. These results are consistent with the observation that even
      if some of actin monomers do not participate in the ATPase activity directly,
      they can interact with myosin heads and take part in the sliding movement.

PMID- 7647092
TI  - Disruption of the disulfide bridge in azurin from Pseudomonas aeruginosa.
AB  - In the family of small blue-copper proteins azurins are unique in that they
      contain a disulfide bridge close to the amino-terminal end. It is situated in the
      'south' side of the molecule, about 25 A away from the copper. Site-specific
      mutagenesis was used to exchange one or both of the cysteines in the bridge for
      serines in Pseudomonas aeruginosa azurin. In the double mutant Cys3Ser-Cys26Ser
      the Type 1 Cu is converted into Type 2, and the fluorescence of the single
      internal tryptophan shows that it becomes exposed to a polar environment. The
      circular dichroism spectrum indicates a loss of beta-structure. Thus, this
      mutation prevents the correct folding of the protein and the formation of the
      metal-binding site. Single mutants, Cys3Ser or Cys26Ser, can at least in part
      form native-like structures as shown by optical, EPR, fluorescence and CD
      spectroscopy. The Cys3Ser mutant can form a stable intermolecular disulfide bond
      which promotes the native conformation of the protein.

PMID- 7647093
TI  - Purification, characterization and substrate specificity of rat pancreatic
      elastase II.
AB  - A somatostatin-14-degrading activity has been purified to homogeneity from rat
      pure pancreatic juice. This proteinase was concentrated more than 350-fold in a
      four-step procedure including ion-exchange and gel filtration. The final
      preparation contained a single protein with a molecular weight (M(r)) of approx.
      29,000, as determined by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis. The determination of its NH2-terminal sequence led us to
      conclude that the purified proteinase corresponds to the rat pancreatic elastase
      II predicted from the cDNA clone isolated by MacDonald in 1982. This anionic
      proteinase exhibits an isoelectric point of 5.6 and does not contain any
      carbohydrate moieties in its structure. The proteinase is sensitive to the
      trypsin inhibitors soybean trypsin inhibitor and N alpha-tosyl-L-lysine
      chloromethyl ketone and also to 3,4-dichloroisocoumarin, a general elastase
      inhibitor. The cleavage products obtained after hydrolysis of somatostatin-14 by
      the purified elastase, were separated by reversed phase high performance liquid
      chromatography and identified by amino-acid analysis. The primary hydrolysis was
      trypsin-like and consisted in an opening of the cyclic structure of somatostatin
      14 after the Lys-9 residue leading to the formation of a Y-shaped peptide with
      the same amino-acid composition as the native peptide. The initial 'trypsin-like
      specificity' was not observed during the secondary hydrolysis of the Y-shaped
      peptide; indeed the proteinase seemed more specific for a certain motif in the
      native peptide rather than for a specific class of amino acid, this last kind of
      selectivity is commonly observed with trypsin and chymotrypsin. In order to
      establish that the proteinase possesses an extended recognition site on the
      substrate rather than a specificity for a class of amino acid, the substrate
      specificity of the rat pancreatic elastase II was investigated with a series of
      para-nitroanilide peptides. The proteinase exhibits a large specificity involving
      peptide chain of at least four amino acids with a preference for bulky residue in
      P1 or P2. The Km values of 89 microM and 1567 microM obtained for somatostatin-14
      and Suc-Ala-Ala-Pro-Met-pNA, respectively, indicate that elastase II has a
      greater affinity for the natural substrate than for synthetics. This last
      observation along with the substrate specificity of the proteinase leads us to
      propose that elastase II could be specifically involved in the regulation of
      biological functions of somatostatin-14 in the gastrointestinal tract.

PMID- 7647094
TI  - cDNA cloning of a novel brain-specific protein p25.
AB  - A cDNA for a bovine brain-specific protein p25 which had been originally found as
      a major protein in a partially purified fraction of tau protein kinases was
      cloned. The deduced amino-acid sequence consists of 218 amino acids (M(r) 23,472)
      and has no significant homology with previously reported proteins. p25 is a basic
      protein and has a consensus sequence for ATP-binding in the C-terminal region.

PMID- 7647095
TI  - Avian cathepsin B cDNA: sequence and demonstration that mRNAs of two sizes are
      produced in cell types producing large quantities of the enzyme.
AB  - Overlapping cDNA fragments encoding avian cathepsin B were cloned from an
      osteoclast cDNA library and sequenced. The primary structure of the prepro enzyme
      deduced from this sequence has 340 amino acids. The mature portion of the enzyme
      is 80% identical with murine cathepsin B; regions found in other papain
      superfamily enzymes are conserved. In osteoclasts and cultured macrophages, which
      produce large quantities of cathepsin B, mRNAs of 1.8 and 2.4 kb are produced in
      approximately equal quantities, while cells producing smaller quantities of the
      enzyme produce predominantly the 2.4 kb form. This variation in mRNAs suggests
      transcriptional differences related to production of large quantities of the
      enzyme.

PMID- 7647096
TI  - Palmitoylation of endogenous and viral acceptor proteins by fatty acyltransferase
      (PAT) present in erythrocyte ghosts and in placental membranes.
AB  - Human erythrocyte ghosts were shown to have palmitoylating activity which
      acylates both endogenous ghost polypeptides and exogenous proteins derived from
      Semliki Forest virus (SFV). Cell-free fatty acid transfer from [3H]palmitoyl-CoA
      to endogenous protein was greatly enhanced in ghosts when pre-existing fatty
      acids linked to the endogenous acyl proteins were removed by hydroxylamine
      treatment prior to the transfer reaction. In contrast to erythrocyte acyl
      proteins acceptor proteins present in human placental membranes were
      palmitoylated in vitro to a similar extent with or without prior deacylation by
      hydroxylamine treatment. This indicates the presence of large pools of non
      acylated proteins in placenta and small pools in erythrocytes. In testing for the
      protein substrate specificity of the palmitoyl transferase (PAT) present in
      ghosts we found that the SFV acceptor proteins, which are totally unrelated to
      erythrocytes, competed with the palmitoylation of endogenous ghost protein
      acceptors. This palmitoylating enzyme is inhibited by Cibacron Blue, SDS, and
      heat treatment, but stimulated in the presence of low concentrations of mild
      detergent (TX-100). Since PAT operating at the surface membrane of red blood
      cells has properties very similar to those of PAT present in human placental
      microsomes [1], we suggest that only one type of PAT may transfer fatty acids to
      various acylproteins that occur at multiple locations in different tissues [2].

PMID- 7647097
TI  - Epitope mapping for monoclonal antibody against human surfactant protein A (SP-A)
      that alters receptor binding of SP-A and the SP-A-dependent regulation of
      phospholipid secretion by alveolar type II cells.
AB  - Surfactant protein A (SP-A) is a lung-specific glycoprotein in pulmonary
      surfactant and has a collagen like sequence on its N-terminal. SP-A has been
      shown to function as an inhibitor of phospholipid secretion by primary culture of
      alveolar type II cells via cell surface receptor(s) for SP-A. In a previous
      report, we showed that the C-terminal non-collagen like domain of human SP-A
      possessed the biological activities, and that a monoclonal antibody against human
      SP-A, PE10, abolished the biological activity of SP-A (Murata et al. (1993)
      Biochem. J. 291, 71-76). In the present study, we investigated an epitope of SP-A
      for PE10. Western blot analysis with fragmented peptides of human SP-A generated
      by both lysyl endopeptidase and BrCN showed that PE10 reacted with the peptide
      corresponding with Glu202 to the C-terminal but that it lacked the ability to
      bind to the peptide corresponding with Tyr208 to the C-terminal. The antibodies
      against a synthetic peptide (P1) corresponding with Glu202 to Asn217 of human SP
      A inhibited the binding of PE10 to SP-A, suggesting that a similar site was
      recognized by both PE10 and anti-P1 antibodies. Anti-P1 antibodies as well as
      PE10 suppressed the biological activity of SP-A. A direct interaction between P1
      and rat lung membranes, or between P1 and alveolar type II cell membranes was
      shown from the measurement of the fluorescence emission spectra of dansyl-labeled
      P1. These results suggest that an area contiguous to or near the region from
      Glu202 to Met207 of SP-A is important for expressing the biological activities.

PMID- 7647098
TI  - Kinetic behaviour of pancreatic lipase in five species using emulsions and
      monomolecular films of synthetic glycerides.
AB  - In the absence of colipase and bile salts, using tributyrin emulsions or
      monomolecular films of dicaprin at low surface pressure, we observed that no
      significant lipase activity can be measured with Human Pancreatic Lipase (HuPL),
      Horse Pancreatic Lipase (HoPL) or Dog Pancreatic Lipase (DPL). Only Porcine
      Pancreatic Lipase (PPL) and recombinant Guinea Pig Pancreatic Lipase Related
      Protein of type 2 (r-GPL) hydrolyse pure tributyrin in the absence of any
      additive, as well as dicaprin films at low surface pressures. The former lipases
      may lack enzyme activity because of irreversible interfacial denaturation due to
      the high energy existing at the tributyrin/water interface and at the dicaprin
      film surface at low surface pressures. The enzyme denaturation cannot be
      reflected in the number of disulfide bridges, since all the pancreatic lipases
      tested here contain six disulfide bridges, but behaved very differently at
      interfaces. We propose to use the surface pressure threshold, as determined using
      the monomolecular technique, as a criterion for classifying lipases in terms of
      their sensitivity to interfacial denaturation.

PMID- 7647099
TI  - Identification of the bile acid binding proteins in human serum by photoaffinity
      labeling.
AB  - The binding of conjugated and unconjugated bile acids to human serum lipoproteins
      was investigated by density gradient centrifugation and photoaffinity labeling
      studies. The binding of bile acids to high-density lipoprotein increased by
      substitution of the 3 alpha-hydroxy group in cholate and taurocholate by a
      photolabile 3-azido or 3-azi-function. The affinity of bile acid derivatives to
      HDL showed the following ranking: 3 beta-azido-7 alpha,12 alpha-dihydroxy-,3,3
      azo-7 alpha,12 alpha-dihydroxy- > 3 alpha,7 alpha,12 alpha-trihydroxy-,11 xi
      azido-3 alpha,7 alpha,12 xi-trihydroxy- > 11 xi-azido-12-oxo-3 alpha,7 alpha
      dihydroxy- > 7,7-azo-3 alpha,12 alpha-dihydroxy-,3 alpha,7 alpha-dihydroxy-,3
      alpha,12 alpha-dihydroxy- > 3 alpha-hydroxy-cholan-24-oic acid. Based on the
      actual serum concentrations of albumin and HDL, a preference of hydrophilic bile
      acids to HDL is evident, the 3-azido- and 3-azi-derivatives showing a 5-23-fold
      higher binding to HDL compared to soluble serum proteins. For the identification
      of the bile acid binding proteins in human blood, photoaffinity labeling with a
      variety of photolabile conjugated and unconjugated bile acid derivatives was
      performed with subsequent analysis of radiolabeled serum proteins by one- and two
      dimensional gel electrophoresis. In addition to albumin and the apolipoproteins A
      I and A-II of high-density lipoproteins (Kramer et al. (1979) Eur. J. Biochem.
      102, 1-9), three further proteins in the lipoprotein free serum fraction of M(r)
      41,000, 50,000 and 83,000 were specifically labeled. By two-dimensional
      electrophoresis and by immunoprecipitation these proteins were identified as
      alpha 1-acid glycoprotein (M(r) 41,000), alpha 1-antitrypsin (M(r) 50,000) and
      transferrin (M(r) 83,000). No binding of bile acids to haptoglobin, alpha 2-HS
      glycoprotein, hemopexin or alpha 1-fetoprotein occurred. In conclusion, these
      studies show that bile acid derivatives bind to several serum proteins in
      addition to albumin and furthermore that the substituent in position 3 of the
      steroid nucleus greatly influences the affinity of bile acids to high density
      lipoproteins.

PMID- 7647100
TI  - Characterization of the kinetics and distribution of N-arachidonylethanolamine
      (anandamide) hydrolysis by rat brain.
AB  - Arachidonoylethanolamide or 'anandamide' is a naturally occurring derivative of
      arachidonic acid that has been shown to activate cannabinoid receptors in the
      brain. Its metabolic inactivation by brain tissue has been investigated.
      Anandamide is hydrolyzed by the membrane fraction of rat brain homogenate to
      arachidonic acid and ethanolamine. The hydrolysis is temperature and pH-
      dependent (pH maximum at 8.5) and abolished by boiling. Anandamide hydrolysis is
      protein dependent in the range of 25-100 micrograms protein/ml; does not require
      calcium and is inhibited by phenylmethylsulfonylfluoride,
      diisopropylfluorophosphate, thimerosal and arachidonic acid. Hydrolysis of 10
      microM anandamide by brain membranes follows first order kinetics; at 30 degrees
      C, the rate constant for anandamide catabolism is 0.34 min-1 mg protein-1. The Km
      for anandamide hydrolysis is 3.4 microM, and the Vmax is 2.2 nmol/min per mg
      protein. Hydrolysis occurs in all subcellular fractions except cytosol with the
      highest specific activity in myelin and microsomes. The distribution of
      anandamide hydrolytic activity correlates with the distribution of cannabinoid
      receptor-binding sites; the hippocampus, cerebellum and cerebral cortex exhibit
      the highest metabolic activity, while activity is lowest in the striatum, brain
      stem and white matter.

PMID- 7647101
TI  - Association of negatively-charged phospholipids with low-density lipoprotein
      (LDL) increases its uptake and the deposition of cholesteryl esters by
      macrophages.
AB  - LDL, the major carrier of cholesterol in blood, is poorly metabolized by
      macrophages. In contrast, macrophages can recognize and endocytose anionic
      phospholipids such as phosphatidylserine, phosphatidylglycerol and cardiolipin.
      Since macrophages can take up large amounts of these phospholipids, experiments
      were performed to ascertain whether pre-incubation of native LDL with negatively
      charged phospholipids would enhance the metabolism of LDL by macrophages. When
      125I-LDL was incubated with cardiolipin liposomes for 18 h at 37 degrees C before
      addition to macrophages, an approx. 40-fold increase of LDL metabolism by these
      cells was observed. Similar results were found when LDL was pre-incubated with
      phosphatidylserine or phosphatidylglycerol; however, pre-incubation of LDL with
      phosphatidylcholine liposomes did not lead to an increase of LDL metabolism. The
      macrophage uptake of LDL pre-incubated with cardiolipin was reduced to approx.
      40% of control values in the presence of dextran sulfate and fucoidin, inhibitors
      of anionic phospholipid uptake. Cytochalasin D, an inhibitor of phagocytosis,
      reduced the lysosomal degradation of LDL pre-incubated with cardiolipin to
      approx. 10% of control values. When the LDL-cardiolipin mixture was
      chromatographed on agarose gel, two peaks containing LDL were observed in the
      elution profile: the first peak appeared at the void volume and the second peak
      was detected just ahead of native LDL. The LDL in both peaks was much more
      extensively metabolized by macrophages than was native LDL; the LDL in the first
      peak was metabolized at a rate that was 8 times the second peak. The results
      demonstrate that negatively-charged phospholipids can form a complex with LDL
      which facilitates its phagocytosis by macrophages.

PMID- 7647102
TI  - Photochemical labeling of human erythrocyte membranes with radioiodinatable
      azidosalicylic acid derivative of globoside.
AB  - In an attempt to define glycolipid functions we have prepared photoactivatable,
      iodinatable derivative of globoside and used it for photoaffinity labeling of
      human erythrocyte membranes. Lysogloboside (Gb4Sph) was prepared from globoside
      through deacylation in methanolic KOH followed by re-N-acetylation of
      galactosaminyl residue. The NH2 group of sphingosine residue in Gb4 Sph reacted
      with N-hydroxysuccinimidyl-4-azidosalicylic acid resulting in the formation of
      Gb4Sph-ASA which was purified by preparative tlc and column chromatography. It
      migrated on tlc as a single spot in two solvent systems, was susceptible to leech
      ceramide glycanase and could be radioiodinated to a specific radioactivity of
      about 200 Ci/mmol. Gb4Sph-[125I]ASA was incorporated into human erythrocytes in a
      time and concentration-dependent manner. Before photolysis 96% of the Gb4Sph-ASA
      could be removed with albumin but not with trypsin. After photolysis about 50% of
      the label was firmly bound to erythrocytes being resistant to albumin and trypsin
      treatment. The label was distributed between membrane proteins and lipids in
      about 1:2.3 ratio. Photolabeled proteins were analyzed by SDS-PAGE followed by
      autoradiography and immunostaining. Most of the radioactivity was detected in
      band 3 and its proteolytic fragments irrespective of the duration of photolysis.
      Photolabeling of erythrocyte lipids was demonstrated by Sephadex LH-20 column
      chromatography.

PMID- 7647103
TI  - 1,25(OH)2-vitamin D-3 stimulates phospholipase A2 activity via a guanine
      nucleotide-binding protein in chick myoblasts.
AB  - The steroid hormone 1,25(OH)2-vitamin D-3 [1,25(OH)2D3] stimulated phospholipase
      A2 (PLA2) activity in embryonic chick myoblasts releasing [3H]arachidonic acid
      from the sn-2 position of phospholipids. GTP-binding protein mediation of
      1,25(OH)2D3-dependent PLA2 activity was investigated in cells prelabeled with
      [3H]arachidonic acid. AIF4-, a G-protein activator, mimicked 1,25(OH)2D3
      stimulated arachidonic acid release from myoblasts in a dose-dependent manner.
      Consistent with the involvement of a G-protein in the activation of PLA2 by the
      hormone, guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S), a stable GTP analogue
      which activates G-protein mediated signals, strongly enhanced arachidonic acid
      release in myoblasts. Guanosine 5'-O-(2-thiodiphosphate) (GDP beta S), which
      competitively inhibits G-protein activation by GTP and its analogues, abolished
      1,25(OH)2D3-dependent arachidonic acid release. Bordetella pertussis toxin
      pretreatment significantly suppressed the hormone action whereas cholera toxin
      had minor effects on 1,25(OH)2D3 action. Hormone-induced activation of PLA2 was
      mimicked by the Ca2+ ionophore A23187 and blocked by nifedipine, but was
      unaffected by neomycin, a phospholipase C inhibitor, ruling out the contribution
      of phosphoinositide metabolism to arachidonic acid release. These results suggest
      that 1,25(OH)2D3-stimulation of PLA2 activity in embryonic chick myoblasts is
      mediated by a pertussis toxin-sensitive GTP-binding protein coupled to influx of
      extracellular calcium.

PMID- 7647104
TI  - Vitamin C prevents metal ion-dependent initiation and propagation of lipid
      peroxidation in human low-density lipoprotein.
AB  - Lipid peroxidation and oxidative modification of low-density lipoprotein (LDL)
      have been implicated as causal factors in the pathogenesis of atherosclerosis,
      and prevention of LDL oxidation by antioxidants may be an effective strategy to
      inhibit the progression of the disease. We investigated the effects of the
      reduced form of vitamin C (L-ascorbic acid, AA) and its two-electron oxidation
      product (dehydro-L-ascorbic acid, DHA) upon metal ion-dependent oxidative
      modification of human LDL. We found that low micromolar concentrations of both AA
      and DHA protect LDL against oxidation induced by Cu2+ or by hemin and hydrogen
      peroxide. In a dose-dependent manner, AA and DHA prevented the initiation of
      lipid peroxidation in LDL, as determined by a sensitive and selective assay for
      lipid hydroperoxides utilizing HPLC with chemiluminescence detection. AA and DHA
      also preserved the LDL-associated antioxidants alpha-tocopherol, beta-carotene,
      and lycopene, but not ubiquinol-10. Furthermore, AA was able to stop propagation
      of lipid peroxidation in LDL, whereas DHA lacked this ability. The addition of 60
      microM AA to LDL containing up to 38 nmol/mg protein of pre-formed lipid
      hydroperoxides led to their rapid disappearance; this activity of AA was
      dependent on the presence of redox-active copper, but did not lead to the
      formation of lipid hydroxides, the reduced form of lipid hydroperoxides. Our data
      show that in Cu(2+)-exposed LDL (i) vitamin C primarily spares, rather than
      regenerates, alpha-tocopherol and other endogenous antioxidants, except for AA
      and DHA prevent initiation of lipid peroxidation in LDL; and (iii) AA can
      terminate lipid peroxidation, thereby protecting partially oxidized LDL against
      further oxidative modification.

PMID- 7647105
TI  - Incorporation of bovine adrenal 3 beta-hydroxy-5-ene steroid dehydrogenase/delta
      5-delta 4 isomerase into phospholipid vesicles.
AB  - 3 beta-Hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase (3 beta-HSD/I) and
      cytochrome P-450C21 were co-purified from bovine adrenocortical microsomes by an
      improved method. The 3 beta-HSD/I was successfully incorporated into liposomal
      membranes in which the enzyme activity was greatly stabilized. Enzymatic
      activities and kinetic parameters of the 3 beta-HSD/I proteoliposomes were almost
      the same as those of the solubilized form.

PMID- 7647106
TI  - Oxygen free radicals and human disease.
AB  - Oxygen free radicals are very reactive molecules which can react with every
      cellular component. They are normally produced in organisms being involved in
      various biologic reactions. However, too high levels of these partially-reduced
      O2 species can give rise to functional and morphologic disturbances in cells.
      There is evidence to implicate oxygen free radicals as important pathologic
      mediators in many human disease processes.

PMID- 7647108
TI  - An in vitro system for studying RNA-protein interaction: application to a study
      of yeast ribosomal protein L1 binding to 5S rRNA.
AB  - Previous attempts to study the binding of yeast ribosomal protein L1 with 5S rRNA
      in vitro have been impeded by the failure to form RNA-protein complexes with
      purified protein and RNA. To circumvent this difficulty, we have developed an in
      vitro system that allowed RNP formation. The system involved in vitro expression
      of the protein L1 from its cloned gene in the presence of exogenous yeast 5S
      rRNA. A protein of the expected size (34 kDa) was synthesized by in vitro
      transcription and translation. A specific 5S rRNA-protein L1 complex (RNP) was
      formed when the rRNA molecule was present during protein L1 synthesis. However,
      the full-length protein L1 failed to bind 5S rRNA. The extent of RNP formation
      was proportional to the concentration of the exogenous yeast 5S rRNA in the
      reaction. The RNP displayed properties identical to those isolated from mature
      60S ribosome subunits. Addition of yeast 5.8S rRNA did not result in the
      formation of a specific RNP. Using this in vitro system, we examined the ability
      of several deletion mutant proteins to bind yeast 5S rRNA and concluded that
      protein L1 missing residues 261 to 295 from the C-terminus could not bind yeast
      5S rRNA. This in vitro system should be useful for future studies on the
      molecular nature of 5S rRNA-protein L1 interaction.

PMID- 7647107
TI  - Production and purification of active FGF2 via recombinant fusion protein.
AB  - Basic fibroblast growth factor (FGF2) is involved in both cell proliferation and
      differentiation processes. Heparin may interfere in the stability and biological
      activities of FGFs. However, it is difficult to obtain FGF preparation without
      traces of heparin since heparin affinity chromatographies are routinely used to
      prepare this growth factor. We have therefore devised a means of production of
      active recombinant FGF2 devoid of heparin traces. The bovine FGF2 gene was
      inserted into the pMAL-c prokaryotic expression vector and the recombinant
      protein was synthesised as a fusion product between the maltose binding protein
      (MBP) and FGF2. Purification of the FGF2 fusion protein was performed by an
      amylose affinity chromatography. Yields were similar to those obtained by using a
      traditional heparin affinity column purification procedure. The fusion protein
      (MBP-FGF2) and the cleaved-off FGF2 were tested for some of their biological
      properties and compared to recombinant FGF2 purified by heparin affinity
      chromatography. Mitogenic activity on Chinese hamster lung fibroblasts (CCL39)
      and neurite outgrowth on pheochromocytoma culture cells (PC12) were used as
      biological assays. The cleaved-off FGF2 was as active as commercially available
      recombinant FGF2 (ED50 at 0.16 and 0.04 nM respectively). However MBP-FGF2 was
      less active (ED50 at 0.9 nM) in both tests.

PMID- 7647109
TI  - Transbilayer distribution of phosphatidylcholine and phosphatidylethanolamine in
      the vacuolar membrane of Acer pseudoplatanus cells.
AB  - The distribution of phosphatidylethanolamine (PE) and phosphatidylcholine (PC)
      among the outer and inner monolayers of the vacuolar membrane of Acer
      pseudoplatanus was investigated using isolated vacuoles, chemical labelling
      agents (trinitrobenzene-sulfonate and fluorescamine), phospholipase A2 from bee
      venom, phospholipase C and phospholipase D. Treatments were performed with intact
      or sonicated vacuoles. Analysis of the transbilayer distribution of PC and PE in
      the vacuolar membrane of Acer was limited by phospholipid fractions which were
      inaccessible to the probes. Lipid-protein interactions and modification of the
      surface charge and surface pressure in the membrane layers during treatments may
      obviously exert a strong influence on labelling or hydrolysis of membrane
      phospholipids. However, simultaneous treatments carried out with phospholipase A2
      and phospholipase C show that PE is approximately 20% more abundant in the outer
      monolayer than in the inner monolayer and PC is equally distributed between both
      leaflets of tonoplast. Compared to the phospholipids asymmetrical distribution
      observed in plasma membrane of erythrocyte, the vacuolar membrane of Acer is not
      characterized by a marked asymmetrical distribution of its major phospholipids.

PMID- 7647110
TI  - Stimulation of translation by reactive oxygen species in a cell-free system.
AB  - Wheat germ lysate was used as a model system for in vitro translation. We show
      that an increase of the exchange surface between the reaction mixture and the
      atmosphere enhanced the amount of incorporated cysteine, indicating that early
      arrest of protein synthesis previously observed in such a system was due to
      oxygen starvation in the reaction mixture. This hypothesis was confirmed since
      the amount of proteins synthesized and the rate of translation increased when
      oxygen was added. We show that an addition of hydrogen peroxide to the
      translation mixture had the same effect as oxygen, allowing us to postulate that
      stimulation could be due to a common property between both molecules: the
      oxidizing behaviour. Free radicals in in vitro translation were believed to be
      involved since the utilization of iron chelating agents inhibited translation.
      This hypothesis was emphasized by the positive effect of a free radical
      generating system and the negative effect of free radical scavengers. These
      experiments suggest that the superoxide radical plays an important role in in
      vitro translation.

PMID- 7647111
TI  - Phospholipid fatty acid composition of hepatopancreatic brush-border membrane
      vesicles from the prawn Penaeus japonicus.
AB  - Brush-border membrane vesicles (BBMV) were isolated from prawn hepatopancreas as
      we previously described (Muriana et al (1993) J Biochem 113, 625-629). The
      characterization of hepatopancreatic BBMV (hBBMV) by monitoring the activity of
      marker enzymes indicated a relatively pure apical membrane preparation reduced in
      basolateral contamination. Phospholipid composition of hBBMV was examined by the
      Iatroscan TLC/FID technique, whereas the fatty acid profile of phospholipids was
      examined by capillary gas chromatography. Phosphatidylcholine and
      phosphatidylethanolamine are the principal phospholipids of these membranes. The
      major fatty acids of phospholipids are palmitic (16:0), palmitoleic (16:1n-7),
      stearic (18:0), oleic (18:1n-9), eicosapentaenoic (20:5n-3) and docosapentaenoic
      (22:5n-3) acids. Individual phospholipids are characterized by distinct fatty
      acid compositions, but display a similar ratio of unsaturated-to-saturated fatty
      acids and a similar unsaturation index.

PMID- 7647112
TI  - A structure-based multiple sequence alignment of all class I aminoacyl-tRNA
      synthetases.
AB  - The superimposable dinucleotide fold domains of MetRS, GlnRS and TyrRS define
      structurally equivalent amino acids which have been used to constrain the
      sequence alignments of the 10 class I aminoacyl-tRNA synthetases (aaRS). The
      conservation of those residues which have been shown to be critical in some aaRS
      enables to predict their location and function in the other synthetases,
      particularly: i) a conserved negatively-charged residue which binds the alpha
      amino group of the amino acid substrate; ii) conserved residues within the
      inserted domain bridging the two halves of the dinucleotide-binding fold; and
      iii) conserved residues in the second half of the fold which bind the amino acid
      and ATP substrate. The alignments also indicate that the class I synthetases may
      be partitioned into two subgroups: a) MetRS, IleRS, LeuRS, ValRS, CysRS and
      ArgRS; b) GlnRS, GluRS, TyrRS and TrpRS.

PMID- 7647113
TI  - The geometrical analysis of peptide backbone structure and its local
      deformations.
AB  - A proposal to use a unified description of protein structures is presented,
      assuming that all peptide chain conformations (including beta-structure) may be
      considered as helix-derived. In this understanding the beta-conformation of the
      peptide chain may be obtained by extending or unwinding the helical form. A
      unified description could be based on a commonly defined internal axis (Z-axis)
      determined by the averaged direction of the CO bonds in a pentapeptide analytical
      unit. Five parameters were proposed to describe the peptide conformation: i)
      radius of curvature (R), calculated from the position of five consecutive peptide
      bond planes; ii) horizontal angular displacement (H) of the neighboring (i+1-th)
      versus the central amino acid residue (i-th) in the pentapeptide fragment; iii)
      vertical angular displacement (Vi) of the peptide bond plane of the i-th residue
      versus the Z-axis; iv) vertical angular displacement (Vi+1) of the i+1-th peptide
      plane measured versus the Z-axis; and v) vertical rise (VR) defined for the i+2
      th residue versus the i-th residue. This geometrical analysis was used to study
      the mechanism of a possible transition from alpha R to beta and to alpha L
      transition, based on data taken from the known Phi, Psi distribution in proteins.
      This analysis was also designed and preliminarily used to reveal local peptide
      backbone distortions and their distributions in proteins for structure-function
      relation studies.

PMID- 7647114
TI  - Identity of macromolecules present in the extracellular slime layer of
      Staphylococcus epidermidis.
AB  - The extracellular slime layer of Staphylococcus epidermidis ATCC 35983 contains:
      a) two non-anionic carbohydrate containing proteins degradable with papain of
      molecular masses 250 and 125 kDa; b) a polydisperse but homogeneously-charged
      acidic population with M(r) ranging from 120,000 to 35,000 (average M(r) (80,000)
      containing a polysaccharide covalently bound to a small peptide; c) a papain
      degradable macromolecule (molecular mass 60 kDa) bearing acidic carbohydrates
      covalently bound to protein; and c) two acidic polysaccharides strongly retained
      by the anion-exchange column; one polysaccharide is sulphated and has a molecular
      mass of 20 kDa; the other has a higher charge density and a molecular mass of
      12.5 kDa. The results obtained clearly demonstrate the presence of discrete
      macromolecules in the extracellular material of slime-producing S epidermidis,
      the majority of which contain acidic carbohydrates, whose biological role remains
      to be elucidated.

PMID- 7647115
TI  - Small intestinal manifestations of HIV infection.
AB  - The small intestine is a common site of involvement in patients infected with the
      human immunodeficiency virus (HIV). Although there are numerous mechanisms by
      which small intestinal disease may occur in HIV infected patients, the resulting
      clinical manifestations of these disorders are remarkably similar and include the
      development of diarrhoea, weight loss and nutrient deficiencies. In fact, the
      original designation of AIDS in African countries as the 'slim disease'
      underlines the importance of small intestinal involvement (most likely secondary
      to parasitic infections) which commonly occurs in Third World Countries. The
      current review will provide a clinically oriented overview of small intestinal
      disease in patients infected with HIV. Because specific data on treatment of
      small intestinal diseases in AIDS is often lacking, some presented information is
      based on the author's experience and opinions.

PMID- 7647116
TI  - Reactive arthritis.
AB  - Reactive arthritis (ReA) develops after an infection elsewhere in the body,
      generally in the genitourinary or intestinal tract. Chlamydia trachomatis,
      Yersinia enterocolitica, salmonella, shigella, and campylobacter are frequent
      triggering agents. Between 60% and 90% of patients are positive for HLA-B27. The
      arthritis occurs within 4 weeks of the primary infection and is oligoarticular
      and asymmetric. Extra-articular manifestations include mucocutaneous symptoms,
      ocular inflammation, and urethritis. The average duration of arthritis is 4 to 5
      months but two-thirds of patients have symptoms for more than a year. Bacterial
      antigens have been found in synovial specimens from patients with ReA, but
      cultures are sterile. The treatment of ReA comprises non-steroidal anti
      inflammatory drugs, intra-articular steroid injections, and physical treatment.
      Short-term antibiotic treatment has no effect in manifest ReA, whereas a tendency
      to improvement has been seen with treatment over months, at least after chlamydia
      infection.

PMID- 7647117
TI  - Gonorrhoea now.

PMID- 7647118
TI  - Management of Pneumocystis carinii pneumonia. The Jefferiss Wing Therapeutics and
      Protocols Group.

PMID- 7647119
TI  - Respiratory 'grey case'.

PMID- 7647120
TI  - Predictors of AIDS knowledge, condom use and high-risk sexual behaviour among
      women in Dar-es-Salaam, Tanzania.
AB  - Reducing the number of sex partners and using condoms are the major means for
      individuals to protect themselves from STDs and AIDS in sub-Saharan Africa. To
      identify predictors of having only one sex partner in the last year and to assess
      knowledge and use of condoms among women of reproductive age in Dar-es-Salaam,
      Tanzania, we interviewed 2285 women at 3 representative family planning clinics
      between February 1991 and June 1992. After interview, blood and genital specimens
      were collected for laboratory diagnosis of HIV and other sexually transmitted
      diseases (STDs). Although knowledge of sexual transmission of AIDS was very high,
      less than a half of the respondents (42.8%) mentioned use of condoms as an AIDS
      preventive measure. Younger and more educated women were more likely to mention
      use of condoms for AIDS prevention, however only 4.6% of women interviewed were
      regular users of condoms, while 19.8% were occasional users. The majority of
      women who had never used a condom (57.5%) reported not using condoms because 'men
      did not like them'. Condom use was positively associated with increasing level of
      education and increasing number of sexual partners. 14.8% of women reported
      having more than one sex partner in the last year; this behaviour was more likely
      among cohabiting women (increased by 210%); HIV-positives (increased by 120%);
      and among women with STDs (increased by 50%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7647121
TI  - A study of the prevalence of male intrameatal warts using meatoscopy in a
      genitourinary medicine department.
AB  - A cross-sectional study is undertaken to determine the prevalence of male
      intrameatal and distal urethral warts, using meatoscopy. A group of 169 patients
      presenting for anogenital warts and a group of 74 unselected patients attending
      the Department for a variety of reasons during the study period, were examined.
      Twenty-one patients (13.5%) out of 155 patients with anogenital or related warts
      had external warts at the meatus. Of these 21 cases, 12 (57.1%) had further
      extension of their warts into the distal urethra. Fifteen other cases of
      intrameatal and distal urethral warts were detected in the absence of external
      warts at the meatus. Twenty-three cases out of 107 males with genital warts
      (21.5%) were found to have intrameatal or distal urethral warts, thus reflecting
      the common occurrence of these lesions. A highly significant association between
      the presence of intrameatal/distal urethral warts and the presence of male
      genital warts was found (P = 0.003). One hundred and fifty-three repeat
      meatoscopic examinations were carried out, 6 weeks after their first examination.
      Three new cases of intrameatal/distal urethral warts were found. Intrameatal and
      distal urethral warts occurred from a depth of 5 mm to 25 mm. One hundred and
      eighty-three female partners of the study patients were examined. An association
      between the presence of intrameatal/distal urethral warts and female anogenital
      warts was found (P = 0.028). No corroborating association between the presence of
      male and female anogenital warts was found (P = 0.47). This observation may have
      a bearing on disease transmission and control. The detection of
      intrameatal/distal urethral warts will be important in achieving successful
      treatment of male anogenital warts.

PMID- 7647122
TI  - Injection drug use-related HIV healthcare--problems and management in Edinburgh.
AB  - The relatively high numbers of patients with IDU-related HIV in Scotland has
      resulted in considerable management difficulties not previously experienced by
      other medical units. Chronic physical ill health in drug users is becoming
      commoner with the advent of HIV and other centres are now experiencing the type
      of problems that the Regional Infectious Disease Unit (RIDU) in Edinburgh has
      faced over the last 10 years. Very little has been published concerning the
      difficulties of managing patients who use drugs and have a physical illness in
      medical units in the UK. This paper presents examples of common problems together
      with the RIDU's experience of management in the hope that it will help others to
      deliver effective and efficient physical and mental health care to patients with
      drug problems.

PMID- 7647123
TI  - Outreach STD clinics for prostitutes in Edinburgh.
AB  - This paper describes the establishment of Genito-Urinary Medicine outreach
      clinics based in 2 drop-in centres for female prostitutes in Edinburgh; 242 women
      have received medical care at these outreach clinics. STD screening has been
      carried out on 160 (63%), detecting one case of gonorrhoea, 11 cases of
      chlamydia, 11 cases of genital warts, and 2 cases of recurrent genital herpes.
      With regards to HIV serostatus, 8 women were already known to be HIV seropositive
      and 18 were known to be seronegative. One hundred and fifteen women have been
      tested at the outreach clinics, yielding one positive result. The serostatus of
      91 women is unknown. There have been 42 pregnancies, some of which were conceived
      through client contact. The prevalence of STDs including HIV is low and would
      suggest that condom usage is high. However, this level of usage is associated
      with significant numbers of unwanted pregnancies. Prostitutes in Edinburgh do not
      appear to act as a significant focus for dissemination of HIV infection.

PMID- 7647124
TI  - Female sexual health problems in a drug dependency unit.
AB  - The Government of the United Kingdom has produced a strategic plan called the
      Health of the Nation aimed at achieving better health in key areas including a
      reduction in rates of unwanted pregnancies, sexually transmitted diseases and
      cervical cancer. Conventional health care systems fail some groups with special
      needs. This cross-sectional interview study was undertaken to determine the level
      and type of contraceptive use, and the attitudes of female opiate abusers to the
      use and availability of contraceptives and cytology services. The subjects were
      201 opiate-dependent women enrolled in a methadone maintenance programme in a
      large drug dependency unit: 169 (84.5%) were sexually active and 65 (44.2%) of
      non-pregnant sexually active women did not use a contraceptive method. Thirty-six
      (43.9%) of those using a contraceptive were using condoms, with which the
      majority were dissatisfied. Sixty-one (30.3%) had never had a cervical cytology
      smear and of those who had, 21.4% reported an abnormal result. The contraceptive
      practices and uptake of cervical screening services by the women studied are
      inadequate, reflecting poor use of conventional health care services. In addition
      to providing information on safer sexual practices, particularly promotion of
      condom use, we suggest that drug dependency units should expand their role to
      provide educational and preventative services to include aspects of women's
      health.

PMID- 7647125
TI  - Clinical parameters associated with recalcitrant oral candidosis in HIV
      infection: a preliminary study.
AB  - Clinical resistance in oropharyngeal candidosis is an increasingly significant
      management problem in HIV-seropositive patients. This study was undertaken to
      identify predisposing risk factors including the isolation of particular species
      of Candida which may be associated with the development of clinical resistance.
      The effect of particular antifungal prescribing regimens was also assessed. Data
      were compiled by chart review of 2 groups, each of 10 HIV-seropositive CDC stage
      IV patients with recurrent oropharyngeal candidosis. All patients had swabs taken
      at intervals during treatment and all candida isolates were species typed. The
      patients in group 1 exhibited candida infections which did not respond clinically
      to standard therapeutic regimens. The second patient group did respond to
      standard oral antifungal therapies. An association was found between the frequent
      utilization of azoles, particularly fluconazole and the development of clinically
      resistant oral candidosis. The number of candida isolates grown from the initial
      swab was also significantly related to the development of resistance.

PMID- 7647126
TI  - Prevalence of Epstein-Barr virus and human papillomavirus in cervical samples
      from women attending an STD-clinic.
AB  - A group of 91 women attending the STD-clinic, Department of Dermatovenereology,
      Sahlgrenska Hospital, Gothenburg, were screened for EBV DNA and HPV DNA of the
      cervix with the PCR-technique. Presence of EBV DNA was demonstrated in 35 (38%)
      women and HPV DNA in 30 (33%) women. Fourteen (15%) women had both EBV DNA and
      HPV DNA present. Without the colposcope 20 of these women had macroscopic signs
      of HPV infection on the vulva and/or vagina and 71 had no signs of infection.
      Presence of EBV DNA was not correlated to clinical signs of HPV infection.

PMID- 7647127
TI  - Pharyngeal flora in a sexually active population.
AB  - During a 7-week period 1141 patients attending the Genitourinary Clinic at
      Charing Cross Hospital completed a brief questionnaire and had pharyngeal swabs
      cultured for Neisseria spp, beta-haemolytic streptococci, corynebacterium and
      yeasts. The study included 397 heterosexual men, 492 heterosexual women, 189
      homosexuals, 41 lesbians and 22 bisexual men and women. Four hundred and sixty
      patients (40%) admitted oro-genital contact in the preceding 2 weeks. The
      meningococcal carriage rate was 11.6%. Homosexuals had the highest carriage 23.8%
      and heterosexual females the lowest 5.9%. Significant differences in carriage
      rates were found between homosexual and heterosexual men (P < 0.0001),
      heterosexual men and women (P < 0.005) and between lesbian and heterosexual women
      (P < 0.025). Recent oro-anal contact significantly increased meningococcal
      isolation (P < 0.001). A significant association between beta-haemolytic
      streptococci and concomitant meningococcal carriage was also found (P < 0.01).
      Sexual orientation and oro-genital contact influences both meningococcal and
      pharyngeal yeast isolation and should be considered when interpreting pharyngeal
      culture results.

PMID- 7647128
TI  - Haemorrhagic ulcerative colitis due to Isospora belli in AIDS.

PMID- 7647129
TI  - An audit of patients' views in Yorkshire genitourinary medicine clinics.

PMID- 7647130
TI  - Patients with HIV dying in Edinburgh: an audit of preference and place of death.

PMID- 7647131
TI  - Toxoplasma seroprevalence in HIV-positive patients in West Midlands.

PMID- 7647132
TI  - The cost effectiveness of hospital-based 25% podophyllin vs home-based 0.5%
      podophyllotoxin in the treatment of anogenital warts.

PMID- 7647133
TI  - Influence of emergence of viral resistance on HIV treatment choice.

PMID- 7647134
TI  - Gender identity disorder and HIV disease.

PMID- 7647135
TI  - [Factors affecting recurrence after surgical treatment of Crohn disease].
AB  - Surgery does not cure Crohn's disease, but only its complications, as the
      recurrence rate that requires a new intervention is 6% per year. The resections
      performed by the surgeon should be as limited as possible, in order to avoid the
      consequent malabsorption. The identification of two forms of Crohn's disease,
      with different aggressiveness, has found that the stricturoplastic is an
      encouraging way of treatment for those forms with a prevalent stenotic component.
      A lot of studies have evaluated the relationships between recurrences and
      resections on margins microscopically free or affected by the disease. The aim of
      this study was a retrospective verification of the influence of any possible
      microscopical residue of the disease on the recurrence rate, evaluating whether
      the two different forms of aggressiveness of the disease (presence of stenosis or
      fistula) can influence the rate and precocity of the recurrence onset. In 37
      patients operated for the first time of ileal or ileocolic resection, the overall
      recurrence rate was 18.9%; neither the presence of microscopically affected
      margins nor the presence of fistulas or stenosis has showed to have an influence
      on the onset of the recurrences. The only data that emerged is a greater
      precocity of the onset of recurrence in those patients whose disease was
      characterised by the presence of enteric fistulas. The forms in which fistulas
      and perforations were evident showed a recurrence rate not significantly higher
      than that of forms with stenosis only, but the period of time free from the
      disease was notably longer for the latter. In the end, patients in which typical
      granulomas were present showed a recurrence rate of just 9%, compared to 23% of
      patients in which granulomas were absent. MATERIALS AND METHODS. From 1980
      through 1992, 61 patients affected by Crohn's disease were operated. There were
      39 men and 22 women (mean age: 40.4 years). The mean length of the follow-up was
      55.5 months. It was the first operation for 43 patients, while 9 had already
      undergone surgery in other hospitals; 9 patients showed anorectal complications.
      The operations performed on the patients for the first time have been ileal
      resection in the following localizations: duodenum-jejunum 4, jejunum and ileal
      34, colic 5; the recurrences treated have been ileal-jejunum in 7 cases and colic
      in 2. In 2 cases of recurrence a stricturoplastic has been performed. RESULTS.
      The operative mortality was of 3 patients: 2 due to sepsis for anastomotic
      dehiscence and 1 to systemic mycosis. Four postoperative fistulas were observed.
      Recurrence of the disease occurred in 13 patients (26.5%), specifically in 21.4%
      of the patients operated for the first time and in 57.1% of those that were
      operated for recurrences. DISCUSSION AND CONCLUSIONS. In the treatment of Crohn's
      disease, it is important to identify any possible group with high risk of
      recurrence in order to undertake an appropriate medical prophylaxis. The results
      concerning the presence of microscopical disease on the resection margins are
      today still controversial. Some groups of authors prefer wide resection margins,
      some others are in favour of restricted resections. Our considerations let us
      assert that in those patients in which the resections have been performed on
      margins with microscopic presence of the disease, the interval before the
      recurrence occurs is not significantly shorter than that of patients with free
      margins. But the patients suffering from Crohn's disease with fistulae, probably
      need medical post-operative therapy to delay recurrences onset.

PMID- 7647136
TI  - [Ulcerative rectocolitis: review of clinical characteristics in patients with
      distal colitis and extended colitis].
AB  - Ulcerative colitis is an inflammatory disease which, starting from the rectum,
      affects more or less extended tracts of the colon. Given that distal and extended
      forms are generally described as a single nosological entity, the authors aimed
      to verify whether there are any clinical differences between the two groups of
      patients with varying extents of disease. A retrospective review was made of data
      relating to 189 patients suffering from ulcerative colitis observed over a 90
      months period. Only 111 cases were included in the study: all patients had
      undergone an endoscopic and histological diagnosis with a follow-up of over one
      year. Seventy-eight patients (41.26%) were excluded from the study because they
      had been lost during follow-up, or follow-up had lasted less than one year, or it
      had not been possible to perform pancolonoscopy. The 111 patients examined were
      subdivided into 2 groups: one (39 patients) with distal colitis, namely involving
      the rectum or recto-sigmoid, and the other (72 patients) with more extended
      disease. The extension of disease was evaluated on the basis of histological
      findings. The mean follow-up was 5 years and 11 months. The two groups were
      comparable for age, sex, number of annual attacks, maximum duration of disease
      free periods, clinical evolution, predominant symptoms, extraintestinal symptoms
      and surgical treatment. Results were processed using Student's t test and the chi
      square test.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7647137
TI  - [Biliopancreatic bypass in the treatment of severe obesity: long-term clinical,
      nutritional and metabolic evaluation].
AB  - Biliopancreatic bypass surgery leads to considerable weight loss and the
      stabilisation over time of the newly acquired body weight. The aim of this study
      was to evaluate the long-term clinical and nutritional conditions of patients
      undergoing this operation. Thirty subjects who had undergone biliopancreatic
      bypass surgery (7 males and 23 females) aged between 20 and 55 years old, with
      body mass indexes between 35 and 80, were examined at yearly intervals (maximum
      follow-up 5 years). Tha following parameters were evaluated at each control: body
      weight, presence of collateral effects, support therapy, main hematochemical
      parameters, nutritional behavior and calorie intake. All patients recorded a
      significant reduction in body weight with a mean weight loss of 28% during the
      first year; these values were confirmed during the second year, whereas body
      weight tended to stabilise in the long-term. Laboratory data showed a significant
      reduction in triglycerides, cholesterol, glycemia in all patients; sideropenic
      anemia appeared in 50% of patients. Mean daily calorie intake was 2,200 kcal/day,
      broken down as follows: glucides 50%, lipids 33%, proteins 17%. The main
      collateral effects reported were: diarrhea, vomit, flatulence, onset of food
      intolerances. The following support therapies were used: iron in 90% of cases,
      calcium in 60% and 30% of patients also underwent surgery. In conclusion,
      biliopancreatic bypass surgery enables a significant weight loss to be achieved
      together with an improved glycolipid status without leading to nutritional
      deficiencies.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7647138
TI  - [Nutritional status of patients with alcoholic liver diseases: comparison of the
      situation in the seventies and at present].
AB  - AIMS. 1) To evaluate the nutritional status of a group of alcohol abusers,
      relatively to their liver function and morphology, and 2) to compare these data
      with those of a previous study carried out by out team ten years ago. According
      to their body weight, 135 alcohol abusers were divided into three groups: normal
      weight, over-weight and under-weight. The severity of their hepatopathy was
      defined as: 1. slight hepatopathy; 2. alcohol-induced hepatitis; 3. alcohol
      induced hepatitis plus cirrhosis; 4 child A cirrhosis; 5. child B cirrhosis.
      RESULTS. 1. The overweight group was homogeneously distributed among the several
      degrees of compensated hepatopathy. 2. There was a marked reactivity to skin
      tests (Multitest) in patients with alcohol hepatitis without cirrhosis,
      independently of nutritional disorders. 3. Only decompensated cirrhosis may cause
      caloric-protein malnutrition; consequently, nutritional disorders due to alcohol
      abuse appear late and they are unlikely to play a leading role in the
      pathogenesis of liver disease due to alcohol abuse. Obesity, on the other hand,
      may facilitate the onset of liver steatosis.

PMID- 7647139
TI  - [Hepatitis E virus: a new infective agent for an old disease].

PMID- 7647140
TI  - [Importance of nutrition in the prevention of correlated diseases].

PMID- 7647141
TI  - [Groove pancreatitis. A case report of chronic focal pancreatitis].
AB  - The "groove pancreatitis" is a special form of segmental chronic pancreatitis
      affecting the "groove" between pancreatic head, duodenum and common bile duct.
      This type of chronic pancreatitis was first described in 1973 and only few cases
      have been reported in literature. Unlike other forms of chronic pancreatitis,
      this is often preceded by peptic ulcers, gastric resections or biliary tract
      diseases; it could be associated with cysts of the duodenal wall and pancreatic
      cysts. Abdominal pain, vomiting due to duodenal stenosis, obstructive jaundice
      and weight loss are the most common presenting symptoms. The radiological
      features show a pancreatic mass similar to a pancreatic head carcinoma and the
      discrimination of groove pancreatitis from pancreatic carcinoma is often
      difficult or even impossible in some patients. We describe a case of groove
      pancreatitis treated with pancreatoduodenectomy, reviewing the clinical and
      radiological features. We remark that the groove pancreatitis is a disease that
      must be known and should be considered in the differential diagnosis of
      pancreatic carcinoma.

PMID- 7647142
TI  - [Synchronous adenomas of the stomach and rectum with severe protein-losing
      syndrome].
AB  - The authors report a case of generalized edema with low colloidal osmotic
      pressure of plasma in an elderly man. After the exclusion of malnutrition and any
      myocadic, renal or hepatic involvement it has been shown that the
      physiopathogenetic mechanism is based on protein-losing enteropathy. Upper and
      lower endoscopy of the gastrointestinal tract reveals double synchronous villous
      adenomas of the rectum and stomach (the latter rare but often associated with the
      former). It is likely that these two lesions may play an important role in the
      development of "anasarca" but only complete reversal of symptoms after surgical
      excision of tumors would demonstrate the causative relationship. The study
      confirms two findings already observed in the literature. The first is the
      increased risk of villous adenoma malignant transformation, especially where
      rarely located, such as in the gastric site. The other depends upon the variety
      of villous adenoma symptomatology. The effects of low plasmatic protein levels
      are prominent in this case, but clinical manifestations range form insidious
      signs of occult bleeding, to frank diarrhea and/or rectal bleeding, up to unusual
      cases of secretory diarrhea with profound dehydration and hypokalemia or
      malabsorption.

PMID- 7647143
TI  - [Use of isocolan in bowel preparation of patients with congestive heart failure].
AB  - The aim of this study was to verify the safety and effectiveness of a
      polyethylene-glycol electrolytes lavage solution (PEG-ELS) in patients with
      delicate fluid and electrolyte balance. Thirteen patients with chronic congestive
      heart failure (CHF) undergoing diagnostic colonoscopy, were asked to drink three
      liters of Isocolan (Bracco s.p.a.) at a rate of 500 ml/30 minutes, 8 hours before
      endoscopic examination. Plasma electrolytes (Na, K, C1), BUN, creatinine,
      glycemia, hematocrit, urine specific weight, arterial pressure, pulse rate, ECG
      and body weight were obtained before and after PEG-ELS supply. Colonic cleansing
      was judged by the same endoscopist as excellent, good or poor. Data, expressed as
      mean (SE), were analyzed by a two-tailed ranked test. PEG-ELS supply did not
      alter fluid and electrolyte balance, since no significant differences were found
      for all laboratory parameters studied. Out of the clinical features, diastolic
      arterial pressure significantly (p = 0.05) raised from 72.3 (3.0) to 78.8 (2.8)
      mmHg and body weight significantly (p = 0.007) increased from 70.7 (3.4) to 71.2
      (3.4) kg. Colon cleansing resulted excellent in 8 patients and good in 5. This
      study shows that Isocolan proved to be safe in patients with CHF and that a slow
      drinking velocity do not impair adequate colon cleansing.

PMID- 7647144
TI  - [Use of prifinium bromide in endoscopic premedication. A double-blind controlled
      study vs hyoscine N-butylbromide].
AB  - Results are reported of double blind controlled clinical trial in patients to be
      subjected to gastroduodenoscopy for diagnostic purposes. Before endoscopic
      examination prifinium bromide or hyoscine N-butylbromide was administered in a
      single dose intravenously as premedication to 30 out patients randomised into two
      groups. In order to evaluate the antispasmodic effects of the drugs on the smooth
      gastroenteric muscle, following endoscopic findings have been examined, before
      and after administration: gastric peristalsis, pilorus status, duodenum
      relaxation and duodenal fold morphology. Our data confirm that both drugs induced
      an appropriate smooth gastroenteric muscle relaxation, enabling an easier
      endoscopic evaluation. Particularly, patients treated with prifinium bromide
      pointed out a better response as far as the pilorus status, reaching complete
      relaxation in 66.7% of subjects versus 26.7% of the control group (p = 0.04). The
      good tolerability of both drugs is also confirmed.

PMID- 7647145
TI  - Acute respiratory failure mediated by reactive drug metabolites.
AB  - Reactive drug metabolites have been implicated in the pathogenesis of adverse
      reactions to the aromatic anticonvulsants. A patient presented with a
      hypersensitivity reaction to the aromatic anticonvulsants which evolved into
      Stevens-Johnson syndrome and was complicated by the presence of adult respiratory
      distress syndrome. When the patient's cells were tested for sensitivity in vitro
      to reactive metabolites of the aromatic anticonvulsants, they were markedly more
      sensitive to metabolites of the aromatic anticonvulsants than were the cells of
      controls (p < 0.05). The adult respiratory distress syndrome has not previously
      been described as a complication of hypersensitivity reactions to the aromatic
      anticonvulsants. In vitro testing also demonstrated cross-sensitivity to the
      anticonvulsants, allowing selection of a therapeutic regimen which would not be
      associated with a risk of exacerbating the hypersensitivity reaction.

PMID- 7647146
TI  - Metabolism of chloramphenicol by glutathione S-transferase in human fetal and
      neonatal liver.
AB  - The glutathione S-transferases of human fetal and neonatal liver catalyse the
      conjugation of glutathione with chloramphenicol at a low but measurable rate. The
      highest rates were 1.30 nmol/min/mg protein in a preterm neonate of 26 weeks of
      gestation and 1.11 nmol/min/mg in a fetus of 22 weeks of gestation, while the
      lowest measurable was 0.1 nmol/min/mg in a fetus of 17 weeks of gestation. The
      activity did not correlate with gestational age, but appeared dependent on the
      concentration of glutathione in the reaction mixture. The rate rose by a factor
      of three, from 0.39 nmol/min/mg protein with no added glutathione to 1.24
      nmol/min/mg with 2 mumol/ml added to the reaction mixture. Chloramphenicol
      aldehyde was detectable in the reaction mixture when a liver extract was
      incubated with glutathione but the proposed intermediate, glutathione
      chloramphenicol, could not be demonstrated. Differences in activity with
      chloramphenicol or a model substrate, under varying conditions, indicate that
      different isoenzymes are concerned with the conjugation of glutathione to the two
      substrates. These data support the hypothesis that when glucuronide conjugation
      is depressed by immaturity, chloramphenicol is metabolised via other pathways.

PMID- 7647147
TI  - Effect of L-arginine infusion on infants with persistent pulmonary hypertension
      of the newborn.
AB  - Nitric oxide (NO) is thought to be a primary mediator of the reduction in
      pulmonary vascular resistance which occurs in the newborn period. L-arginine is
      the precursor for the formation of nitric oxide in the pulmonary endothelium. Low
      serum arginine levels have been reported in infants with persistent pulmonary
      hypertension of the newborn (PPHN). We infused a single L-arginine dose of 500
      mg/kg over 30 min to 5 consecutive infants with PPHN. Ninety minutes after
      infusion we observed an associated rise in PaO2 of 37 to 84 mm Hg and, in 4 of 5
      infants, a reduction in oxygenation index (OI) of 33-50% over the 5-hour period
      following infusion. Infusion was not associated with adverse effects. These
      observations suggest that L-arginine administration may be an effective
      therapeutic alternative in infants with PPHN.

PMID- 7647148
TI  - Scanning gel densitometry of amniotic fluid acetylcholinesterase and
      butyrylcholinesterase: quantification of 'faint-positive' bands in fetal
      malformations.
AB  - The quantification of 'faint-positive' cholinesterases in amniotic fluid was
      performed in 40 patients with positive acetylcholinesterase (AchE) tests. Fetuses
      with anencephaly and open spina bifida presented an AchE/butyrylcholinesterase
      (A/B) ratio of more than 0.3 with clearly dense bands. Fetuses with gastroschisis
      showed a 'faint-positive' AchE band (A/B < 0.3). In 5 fetuses (1 teratoma, 3 open
      spina bifida, 1 unaffected) we found faint AchE and butyrylcholinesterase bands.

PMID- 7647149
TI  - Activities of trypsin and lipase in duodenal aspirates of healthy preterm
      infants: effects of gestational and postnatal age.
AB  - Lipase and trypsin activities were estimated in preprandially aspirated duodenal
      juice of preterm infants with gestational ages between 29 and 32 weeks (group I,
      n = 33) or between 33 and 36 weeks (group II, n = 22) during the first 6 weeks of
      postnatal life. The results were compared with the enzyme activities measured in
      2- to 6-year-old children. There were no significant differences of the mean
      lipase or trypsin activities between the two groups lipase; group I 13.7 +/- 7.9,
      group II 15.9 +/- 9.8 U/ml; trypsin: group I 7.9 +/- 4.7, group II 8.5 +/- 5.1
      U/ml). The activities of both enzymes increased significantly and similarly in
      both groups with postnatal age (lipase: group I r = 0.732, p < 0.01, group II r =
      0.743, p < 0.01; trypsin: group I r = 0.705, p < 0.01, group II r = 0.669, p <
      0.01). At the end of the study the lipase activities of both groups reached
      approximately 35% of the values found in the older children, whereas the trypsin
      activities reached the reference values within the 1st month of life. The results
      indicate an asynchronously age-related development of lipase and trypsin. The
      development of the lipase activity is delayed in comparison to the trypsin
      activity which should be considered in the nutritional management of preterm
      infants.

PMID- 7647150
TI  - Intestinal transport and processing of immunoglobulin G in the neonatal and adult
      rat.
AB  - The proximal intestine of neonatal rats expresses a specific receptor (RFcn) that
      binds immunoglobulin G (IgG) and is no longer expressed after weaning. The aim of
      this study was to quantify and compare the intestinal transport and processing of
      IgG in intestinal fragments with or without RFcn, with the fluid-phase transport
      of horseradish peroxidase (HRP). The mucosal to serosal transport and degradation
      of IgG and HRP were measured in neonatal and adult rats in vitro in Ussing
      chambers. IgG transcytosis occurred without degradation in the proximal intestine
      of neonatal rats, where RFcn is expressed, up to a luminal concentration of 300
      micrograms/ml. At higher mucosal IgG concentrations, a degradative pathway was
      also involved. The immunoreactive IgG fluxes across the proximal intestine of
      neonatal rats were higher than those observed in the distal neonatal intestine or
      those in the proximal and distal adult intestine. The rate of HRP transcytosis
      was higher than that of IgG but it involved a mainly degradative pathway. These
      results suggest that in the proximal intestine of the neonatal rat, where RFcn is
      expressed, the transcytotic rate for IgG is not increased, but the nondegradative
      transport of immunoreactive IgG is favored, especially at low luminal
      concentrations.

PMID- 7647151
TI  - Functioning of the porcine pituitary-adrenocortical axis during neonatal
      development.
AB  - A study was conducted with neonatal boars to measure age-related changes in
      functioning of the pituitary-adrenocortical axis. Pigs were randomly assigned to
      control (n = 7-10/age) or treated (1-min restraint, n = 9-11/age) groups to be
      sampled at either 12, 19, or 26 days of age. Blood samples were taken via
      catheter 10 min before and 3, 10, and 20 min after restraint or at similar time
      intervals in controls. One day later, pigs were killed and adrenal glands
      obtained for ACTH receptor measurements. Basal plasma ACTH concentrations were
      greatest (p = 0.035) on day 12 when compared with later ages, but basal plasma
      cortisol concentrations were comparable at the three ages. Compared with
      controls, restraint elevated incremental plasma ACTH and cortisol responses at
      each age (p < 0.004). On day 12, maximal plasma ACTH (p = 0.0006) and incremental
      cortisol (p < 0.006) responses to restraint were greater than at later ages.
      Binding to adrenal ACTH receptors was greatest (p < 0.05) at day 13, which may
      help explain the apparently increased in vivo response of the adrenal gland to
      ACTH at this time. Restrained pigs had increased growth rates with increasing age
      (p = 0.016) whereas growth rates for control pigs did not differ with age. At day
      27, 24 h after the 1-min restraint, body weights of restrained pigs exceeded
      those of control pigs (p = 0.045). At day 20, adrenal DNA and protein in pigs
      restrained 24 h previously were greater than in control pigs (p < 0.05). These
      data suggest age-related changes in functioning of the pituitary-adrenal axis in
      neonatal boars, and an absence of period during neonatal life when the porcine
      pituitary adrenocortical axis cannot respond to a stressor. The data also
      indicate both rapid and long-term responses of the adrenal to a very modest
      stressor and suggest an extreme sensitivity of neonatal pigs to environmental
      perturbations.

PMID- 7647152
TI  - Ontogeny of dopamine daily rhythms within rabbit brainstem regions.
AB  - To examine the development of daily variations in dopamine levels, we measured
      dopamine concentrations within five distinct brainstem regions in 3- and 21-day
      old, and adult rabbits at 09.30, 15.30, 21.30 and 03.30 h. Dopamine was measured
      by radioenzymatic assay and the dopamine concentration was expressed relative to
      wet tissue weight. In addition to defining the presence of a daily variation in
      the dopamine concentration in the whole brainstem, we were interested in
      identifying brainstem region-specific differences in this daily variation. Our
      data suggest that daily variations in dopamine concentrations are established by
      3 days of life. Analysis of gross brainstem daily variation data suggest a peak
      in the dopamine concentration during the early light phase (09.30 h) for 3-day
      old animals in contrast to a late light phase peak (15.30 h) for 21-day-old
      animals. Adult animals showed a peak in the early dark phase (21.30 h). These
      gross daily variations reflect the net sum of distinct region-specific patterns
      in the dopamine concentration. Analysis by region reflects a region-specific
      ontogeny in the development of daily variations for dopamine. Dopamine is
      involved in cardiorespiratory regulation. The observed developmental patterns may
      relate to the maturation and integration of these physiologic processes.

PMID- 7647153
TI  - Main routes of plasma lactate carbon disposal in the midgestation fetal lamb.
AB  - The turnover rates of plasma lactate, normalized for O2 consumption rate, are
      higher in the fetus than in the adult. This occurs despite very low rates of
      fetal gluconeogenesis which preclude the recycling of lactate carbon into
      glucose. In an effort to establish the main routes of disposal of fetal plasma
      lactate, 12 midgestation ovine fetuses (age 74 +/- 1 days) were infused
      intravenously at constant rate with L-[U-14C]lactate for a 4-hour period. At the
      end of the infusion, the amounts of 14C retained by the fetus and by the
      placenta, and the distribution of the retained 14C in free and protein-bound
      amino acids and in lipids were measured. Of the total 14C infused, 17.0 +/- 1.4%
      was recovered in the placenta, 4.0 +/- 0.3% in the fetal liver, and 15.0 +/- 0.8%
      in the extrahepatic fetal tissues. Of the retained radioactive carbon, 45-57% was
      recovered in the free and protein-bound amino acid fractions and 11-17% in the
      lipid fractions. Approximately 90% of the 14C in the free amino acid fractions
      was present as glutamate/glutamine, serine, glycine, and alanine carbon. In
      conjunction with data on fetal CO2 production from lactate carbon, these results
      demonstrate that the main routes of fetal lactate disposal are oxidation and
      synthesis of nonessential amino acids and lipids.

PMID- 7647154
TI  - 10 Years of research on porcine derived lung surfactant. Proceedings and
      abstracts of the 10th International Workshop on Surfactant Replacement.
      Versailles, France, May 14-16, 1995.

PMID- 7647155
TI  - Pathophysiology and treatment of surfactant protein-B deficiency.
AB  - Surfactant protein B (SP-B) deficiency is an inherited disease of full-term
      newborn infants which leads to lethal respiratory failure within the first year
      of life. Genetic analysis of affected infants has permitted identification of a
      mutation in the SP-B gene found in several unrelated kindreds which disrupts
      pulmonary surfactant composition and function. Lung transplantation has resulted
      in reconstitution of pulmonary surfactant function and long-term survival. SP-B
      deficiency represents the first opportunity to link physiologic characteristics
      of respiratory failure in infancy with specific molecular and cellular defects.
      This linkage will facilitate development of novel strategies for the treatment of
      neonatal respiratory diseases.

PMID- 7647157
TI  - Overview of clinical trials comparing natural and synthetic surfactants.
AB  - This overview summarizes the ten randomized clinical trials that have compared
      different surfactant preparations. Six trials, enrolling 2,450 babies with
      respiratory distress syndrome (RDS), compared Survanta and Exosurf. Babies
      treated with the natural surfactant had lower oxygen requirements for at least 3
      days than those treated with the synthetic surfactant. The babies treated with
      Survanta had lower risks of neonatal mortality (odds ratio, OR, 0.80; 95%
      confidence interval, CI, 0.65-1.00), retinopathy of prematurity (OR 0.68; 95% CI
      0.50-0.94), and death or bronchopulmonary dysplasia (OR 0.84; 95% CI 0.70-1.00)
      when compared to those treated with Exosurf. Infasurf has been compared with
      Exosurf in two studies: one as prophylaxis and the other a rescue trial. Similar,
      although non-significant benefits were found for the natural surfactant. When all
      eight trials were included in a meta-analysis, there was a significant reduction
      in the odds of pulmonary air leaks (OR 0.52; 95% CI 0.41-0.66) for babies treated
      with natural as compared with synthetic surfactants. For seven trials (3,576
      babies) comparing natural and synthetic surfactants to treat RDS (six comparing
      Survanta and Exosurf and one Infasurf and Exosurf), there was a significantly
      reduced risk of neonatal mortality (OR 0.80; 95% CI 0.66-0.97) with natural as
      compared with synthetic surfactant treatment. In two further trials different
      natural surfactant preparations have been compared. Reduced oxygen needs for 24 h
      after treatment were found for Infasurf and Curosurf, respectively, when compared
      to Survanta. Apparent longer-term benefits from these surfactants were not
      statistically significant. Further trials are needed to be certain of the
      differences between various surfactant preparations.

PMID- 7647156
TI  - Potential role of surfactant proteins A and D in innate lung defense against
      pathogens.
AB  - The physiological role of pulmonary surfactant is probably not limited to
      conferring mechanical stability to the alveoli. Increasing evidence suggests that
      surfactant components, in particular the hydrophilic surfactant proteins SP-A and
      SP-D, play potentially important roles in host defense mechanisms. Both SP-A and
      SP-D are collagenous C-type lectins (collectins) that are structurally and,
      perhaps, functionally related to collectins in the circulation. As will be
      discussed in this review, evidence is accumulating that the alveolar collectins
      SP-A and SP-D could be important components of a first-line defense system
      against infiltrating pathogenic micro-organisms and viruses.

PMID- 7647158
TI  - Factors influencing efficacy of exogenous surfactant in acute lung injury.
AB  - Exogenous surfactant is currently being tested as a therapeutic modality for
      patients with acute respiratory distress syndrome (ARDS). Animal studies have
      shown that several factors may influence the efficacy of this treatment modality.
      These factors include the surfactant delivery method used (instillation vs.
      aerosolization), the timing of surfactant treatment over the course of injury,
      the specific surfactant preparation used, and the dose of surfactant
      administered. Each of these factors alone and together may influence the
      interaction of the exogenous surfactant with the host's alveolar environment.
      This, in turn, may dictate how a specific patient responds to a particular
      surfactant treatment strategy. It is suggested that patients at an early stage of
      lung injury will benefit from aerosolized exogenous surfactant whereas large
      quantities of an instilled exogenous surfactant may be necessary at later stages
      of injury. Future studies will clarify how a specific surfactant treatment
      strategy should be chosen for an individual patient with ARDS.

PMID- 7647159
TI  - The surface-associated surfactant reservoir in the alveolar lining.
AB  - A small atmospheric bubble was introduced into a surfactant suspension in a
      captive bubble surfactometer. After film formation to the equilibrium surface
      tension at the bubble air-liquid interface, the bulk phase surfactant was
      depleted by replacing the chamber contents several times with a saline-CaCl2
      solution. The remaining film adsorbed at the bubble surface was then compressed
      stepwise in quasi-static fashion to near zero minimum surface tension. This was
      followed by a series of quasi-static expansion steps to surface tensions slightly
      above equilibrium. The surface tension of films from lipid extract surfactants
      and phospholipid mixtures did not increase in a manner consistent with the
      presence of a single surface monolayer. After the initial, rapid rise in surface
      tension at each expansion step, a decrease in surface tension to a new value was
      observed. This decrease in surface tension is likely due to the adsorption of
      'surplus' material from a 'surface-associated reservoir' into the surface active
      film. The presence of surplus non-monolayer surfactant material in situ at the
      alveolar surface was also demonstrated by electron microscopy. SP-A acted as a
      potent promoter for the movement of excess material (equivalent to 2-3
      monolayers) at the interface into the surface active film. In contrast,
      inhibitory serum proteins prevented the formation of a surface-associated
      reservoir or the adsorption of excess material into a surface active film.

PMID- 7647160
TI  - Inositol monophosphatase inhibitors: a novel treatment for bipolar disorder?

PMID- 7647161
TI  - Brain dysmorphology in adults with congenital rubella plus schizophrenialike
      symptoms.
AB  - Brain morphology was quantified with magnetic resonance imaging (MRI) in adult
      patients with congenital rubella who also had schizophrenialike symptoms. MRIs
      were compared with those of adult early-onset schizophrenic patients without
      congenital rubella and age-matched healthy control subjects. The rubella patients
      had significantly smaller intracranial volumes and shorter stature than the
      schizophrenic patients or the controls; however, both patient groups had smaller
      cortical gray matter, but not white matter, volumes than the control group, even
      when the MRI volumes were corrected for head size and age. In addition, both
      patient groups showed significant enlargement of the lateral ventricles but not
      cortical sulci when compared with expected values of normal adults of the same
      age and head size. Overall, the pattern of dysmorphology was identical in the
      rubella and the schizophrenic groups. The observations in the rubella group are
      consistent with a developmental lesion that limits full brain growth, with the
      small intracranial volume due at least in part to a severe cortical gray matter
      volume deficit. Thus, the brain dysmorphology of congenital rubella may provide
      an instance of prenatal viral infection that models the schizophrenic pattern and
      provides indirect support for a developmental hypothesis of the neuropathogenesis
      of schizophrenia.

PMID- 7647162
TI  - Seizure threshold in electroconvulsive therapy (ECT) II. The anticonvulsant
      effect of ECT.
AB  - To measure the anticonvulsant effects of a course of electroconvulsive therapy
      (ECT), we used a flexible stimulus dosage titration procedure to estimate seizure
      threshold at the first and sixth ECT treatments in 62 patients with depression
      who were undergoing a course of brief pulse, constant current ECT given at
      moderately suprathreshold stimulus intensity. Seizure threshold increased by
      approximately 47% on average, but only 35 (56%) of the 62 patients showed a rise
      in seizure threshold. The rise in seizure threshold was associated with
      increasing age, but not with gender, stimulus electrode placement, or initial
      seizure threshold. Dynamic impedance decreased by approximately 5% from the first
      to the sixth ECT treatment, but there was no correlation between the change in
      dynamic impedance and the rise in seizure threshold. No relation was found
      between the rise in seizure threshold and either therapeutic response status or
      speed of response to the ECT treatment course. These findings confirm the
      anticonvulsant effect of ECT but suggest that such effects are not tightly
      coupled to the therapeutic efficacy of moderately suprathreshold ECT.

PMID- 7647163
TI  - Asymmetrical visual-spatial attentional performance in ADHD: evidence for a right
      hemispheric deficit.
AB  - This study was designed to confirm the presence of a lateralizing deficit in
      visual-spatial attention in children with ADHD, to further characterize the
      nature of this deficit and to specify the likely hemispheric locus of
      dysfunction. Two versions of the covert orienting of attention procedure which
      evaluated separately endogenous and exogenous cuing effects were administered to
      20 unmedicated children aged 9-12 with ADHD and 20 matched controls. Both groups
      also underwent thorough psychiatric assessment and testing using the TOVA and the
      Wisconsin Card Sorting Task (WCST). Children with ADHD showed an asymmetrical
      performance deficit characterized by a loss of costs on controlled (endogenous)
      attentional orienting to invalidly cured left visual field targets. The degree of
      cost asymmetry correlated negatively with the number of categories sorted on the
      WCST. It was concluded that unmedicated children with ADHD show an asymmetrical
      performance deficit on the covert orienting procedure characterized by a
      disruption of right hemispheric attentional mechanisms. This deficit may be
      related to diminished right hemispheric frontal-striatal catecholamine activity.

PMID- 7647164
TI  - Dopamine D2 receptor gene (DRD2) haplotypes and the defense style questionnaire
      in substance abuse, Tourette syndrome, and controls.
AB  - The defence style questionnaire (DSQ) was administered to Caucasian males
      consisting of 123 subjects from a V.A. addiction treatment unit (ATU), 42
      Tourette syndrome (TS) subjects, and 49 controls. For the ATU and TS subjects,
      there was a significant decrease in the mean score for mature defenses and a
      significant increase in mean score for immature defenses compared to controls.
      Many of the individual subscores showed the same significant differences.
      Dopamine D2 receptor (DRD2) gene haplotypes, identified by allele specific
      polymerase chain reaction of two mutations (G/T and C/T) 241 base pairs apart,
      were determined in 57 of the ATU subjects and 42 of the controls. Subjects with
      the 1 haplotype tended to show a decrease in mature and an increase in neurotic
      and immature defense styles compared to those without the 1 haplotype. Of the
      eight times that the subscale scores were significant for haplotype 1 versus non
      1, they were always in this direction. There results suggest that the DRD2 locus
      is one factors controlling defense styles. The difference in the mean scores
      between controls and substance abuse subjects indicates that other genes and
      environmental factors also play a role.

PMID- 7647165
TI  - Stability of plasma GABA at four-year follow-up in patients with primary unipolar
      depression.
AB  - The biology of mood disorders involves gamma-aminobutyric acid (GABA), a
      neurotransmitter whose levels in plasma likely reflect brain GABA activity.
      Previous research has shown that a subset of patients with primary unipolar major
      depression have low plasma GABA levels, which parallels findings from studies of
      cerebrospinal fluid. We have completed a 4-year follow-up on 46 male patients
      with primary unipolar depression. Plasma levels of GABA were stable over this
      time. For the group, mean plasma GABA levels on follow-up did not change
      significantly from entry levels. Plasma GABA levels measured on follow-up were
      significantly (p < .001) correlated with entry levels. Patients with low plasma
      GABA levels (< 100 pmol/ml) on entry into the study were likely to remain low on
      follow-up, and patients with plasma GABA levels in the control range (> or = 100
      pmol/ml) at entry similarly remained in this category (chi 2 = 7.23, p = .007).
      This was true whether or not the patient had recovered from depression on follow
      up. Levels of plasma GABA did not significantly correlate with severity of
      depression at either entry (p = .40) or follow-up (p = .52), nor was there a
      significant correlation between change in plasma GABA and change in the 17-item
      Hamilton Depression Rating Scale score from entry to follow-up (p = .89). These
      data are consistent with the notion that plasma GABA is independent of clinical
      state in patients with primary unipolar depression. Low plasma GABA may be a
      trait marker of illness in a subset of patients with mood disorder.

PMID- 7647166
TI  - Arecoline reverses dexamethasone suppression of cortisol in normal males: a pilot
      study.
AB  - Six normal controls participated in two or three individual, intravenous
      challenges (each separated by 1 week) of saline or one of two doses of arecoline
      at 8 AM following ingestion of 1 mg dexamethasone at 12 midnight the previous
      evening. Individuals differed in their subjective and neuroendocrine responses to
      arecoline. At 2.1 micrograms/kg (n = 4) or 2.8 micrograms/kg (n = 1), four of
      five subjects evidenced dexamethone suppression test (DST) nonsuppression, which
      followed the rise in prolactin. Cholinergic side effects and nausea were minimal.
      At a dose of 4.2 micrograms/kg, four of five subjects evidenced cortisol escape
      from dexamethasone suppression, which was associated with a substantial rise in
      prolactin, some subjective cholinergic symptoms, and little to modest nausea.
      These data are consistent with the notion that cholinergic mechanisms are
      involved in the escape from dexamethasone suppression. Further, arecoline may be
      preferable to physostigmine as a cholinergic agonist, since it appears less
      likely to cause marked cholinergic side effects and significant nausea.

PMID- 7647167
TI  - Depression and immunity: the biochemical interrelationship between the central
      nervous system and the immune system.

PMID- 7647168
TI  - BR-16A restricts development of electroconvulsive shock-induced retrograde
      amnesia.

PMID- 7647169
TI  - Eight-year longitudinal follow-up of P300 and clinical outcome in children from
      high-risk for alcoholism families.

PMID- 7647170
TI  - The relationship between negative symptoms and neuropsychological performance.

PMID- 7647171
TI  - Special issue: EEG in basic and applied settings. Papers from a workshop held in
      Dayton, Ohio.

PMID- 7647172
TI  - Visual information processing: topography of brain electrical activity.
AB  - Multichannel recordings allow the non-invasive assessment of the electrical
      fields of the brain. Topographical analysis of EEG and EPs should not be
      restricted to the qualitative graphical display of maps at many time points
      instead of time series at many recording points. It is mandatory that
      quantitative methods are applied to EEG and evoked potential data in order to
      extract relevant information from such series of maps. For spontaneous EEG data
      the spatial analysis of frequency bands is of major interest while evoked
      potential fields are analyzed in terms of latencies and amplitudes of individual
      components. The computation of global field power, global dissimilarity as well
      as the location of potential maxima, minima or centroids enable a meaningful data
      reduction and the statistical evaluation of the effects of different experimental
      conditions and the comparison of various clinical populations. In a similar way
      multivariate statistical techniques may be employed in order to detect
      characteristic potential field configurations. Topographical methods to analyze
      brain electrical activity are illustrated with multichannel data evoked by
      localized visual stimuli and by stereoscopic stimulation as well as with evoked
      potential data obtained during perceptual learning experiments.

PMID- 7647173
TI  - Quantitative electrophysiological studies of mental tasks.
AB  - A number of pilot studies were performed to evaluate the utility in human studies
      of the so-called 'tracer strategy' previously used extensively in numerous
      experiments by the senior author of this paper. This strategy utilized
      presentation of visual or auditory information intensity modulated at some
      specific repetition rate or 'tracer frequency'. Representation, storage and
      retrieval by the brain of information thus presented is identified by the
      appearance of 'labelled responses' defined as power in the EEG spectrum at the
      tracer frequency or averaged ERP waveshapes extracted from brain electrical
      activity by triggering on the onset of the modulation cycle. This method has been
      applied to scalp recordings obtained during performance of (1) audio-visual
      continuous pursuit tasks in which the target and pursuer were labelled at
      different frequencies and (2) delayed match from sample tasks in which sets of
      letters, numbers or faces modulated at a specific frequency had to be retrieved
      from working memory. Results showed statistically significant appearance of
      labelled responses in different scalp regions, depending upon the nature of the
      cognitive task.

PMID- 7647174
TI  - Concepts and applications of EEG analysis in aviation performance evaluation.
AB  - Quantitative studies of the human EEG during signal detection, flight simulation
      and actual flight performance tasks are reviewed here from the perspective of
      basic animal research on the neurophysiological and functional correlates of
      relevant rhythmic patterns. Evidence is examined which relates distinct EEG
      frequency changes to psychomotor behavior, signal processing and intrinsic
      attentional modulation during complex performance. Findings indicate that the EEG
      can provide a valid and objective index for mental effort but, in addition, may
      reveal task-related cognitive resource allocation, task mastery and task
      overload.

PMID- 7647175
TI  - Sleepiness of civil airline pilots during two consecutive night flights of
      extended duration.
AB  - Sleepiness of civil airline pilots was studied in a two-crew cockpit during two
      consecutive night flights of about 10 h duration each. Sleepiness was assessed by
      EEG recordings and subjective ratings during hourly recurrent short experimental
      phases. On the second night flight, the alertness component that is related to
      the preceding sleep showed a modification due to reduced quality and quantity of
      sleep between flights. The daytime sleep during layover was not sufficient to
      maintain the same alertness level as observed during the initial flight. This
      result is in coincidence with investigations in shift workers starting a period
      of night shifts. It is concluded that improvements such as the introduction of a
      nap schedule should be considered to alleviate spontaneous sleepiness in the
      cockpit.

PMID- 7647176
TI  - Rheoencephalographic and electroencephalographic measures of cognitive workload:
      analytical procedures.
AB  - This investigation demonstrates the feasibility of mental workload assessment by
      rheoencephalographic (REG) and multichannel electroencephalographic (EEG)
      monitoring. During the performance of this research, unique testing, analytical
      and display procedures were developed for REG and EEG monitoring that extend the
      current state of the art and provide valuable tools for the study of cerebral
      circulatory and neural activity during cognition. REG records are analyzed to
      provide indices of the right and left hemisphere hemodynamic changes that take
      place during each test sequence. The EEG data are modeled using regression
      techniques and mathematically transformed to provide energy-density distributions
      of the scalp electrostatic field. These procedures permit concurrent REG/EEG
      cognitive testing not possible with current techniques. The introduction of a
      system for recording and analysis of cognitive REG/EEG test sequences facilitates
      the study of learning and memory disorders, dementia and other encephalopathies.

PMID- 7647177
TI  - Adaptive estimation of single response evoked potentials.
AB  - A new adaptive filtering algorithm and structure is developed to estimate
      response-to-response variations in evoked responses. The evoked responses are
      modeled as the sum of three uncorrelated signal components: ensemble average,
      noise, and stochastic signal variation. A two stage time sequenced filter
      structure exhibiting improved convergence characteristics is developed along with
      a modified P-vector algorithm (mPa) which eliminates the need for a separate
      desired signal electrode. The mPa adaptive filter is tested with simulated and
      human EP data. The mPa filter is able to estimate signal variations from one
      response to the next.

PMID- 7647178
TI  - Towards measurement of brain function in operational environments.
AB  - In operational environments that demand sustained vigilance or that involve
      multiple tasks competing for limited attentional resources, continuous monitoring
      of the mental state of the operator could decrease the potential for serious
      errors and provide valuable information concerning the ergonomics of the tasks
      being performed. There is widespread discussion and appreciation of the basic
      feasibility of utilizing neurophysiological measurements to derive accurate,
      reliable, rapid and unobtrusive assessments of mental state. However, progress in
      transitioning this idea into practical applications has been impeded by the fact
      that at present no convenient, inexpensive and effective means exists to derive a
      meaningful index of brain activity outside of laboratory settings. In this paper,
      we review some recent advances in recording technology and signal processing
      methods that will help overcome this limitation. For example, rapid progress is
      being made in the engineering of recording systems that are small, rugged,
      portable and easy-to-use, and thus suitable for deployment in operational
      environments. Progress is also being made in the development of signal processing
      algorithms for detecting and correcting recording artifacts and for increasing
      the amount of useful information that can be derived from brain signals. Finally,
      results from basic research studies suggest that accurate and reliable inferences
      about the mental load and alertness of an individual can be derived from
      neurophysiological measures in a practical fashion. These research and
      engineering successes suggest that it is reasonable to expect that in the near
      term a basic enabling technology will be deployed that will permit routine
      measurement of brain function in operational environments.

PMID- 7647179
TI  - Processing of multi-dimensional stimuli: P300 component of the event-related
      brain potential during mental comparison of compound digits.
AB  - This study explored the processing of multi-dimensional stimuli during mental
      comparisons by means of behavioral and event-related potential (ERP) measures. As
      multidimensional stimuli served compound digits with separable physical and
      semantic dimensions, each graduated in size. Fourteen adult volunteers were
      presented with the digits zero through nine, which were constructed by suitably
      arranged small digits of the same number set. The subject's task was to decide
      whether the physically larger digit was numerically larger or smaller than the
      physically smaller one. Large and small numbers as well as the numerical
      differences between them appeared, equiprobably, in randomized order. Reaction
      time (RT), frequency of errors, and ERPs registered from Fz, Cz and Pz (time
      constant 5.00 s; 30 Hz frequency cut off) were selectively averaged according to
      three dimensions (i) the numerical differences between simultaneously presented
      large and small digits, (ii) the 10 physically large digits, and (iii) the 10
      physically small digits. As a reflection of the symbolic distance effect, the
      mean RTs and errors decreased and the P300 amplitude increased with increasing
      differences between the numbers compared. The P300 amplitude changed in a U
      shaped function of the numerical value of the physically large digits. This
      result is in accordance with the adaptation-level hypothesis and indicates that
      prior to numerical comparisons the physically large numbers were primarily
      encoded and arranged into the internal number scale. The fact that the U-shaped
      amplitude trend was found for the physically large but not for the physically
      small digits is interpreted as an expression of the advantage of global
      information. The approach of separation task-relevant stimulus dimensions on the
      basis of P300 changes is proposed as an informative method for the study of multi
      dimensional-stimulus processing in multi-task environments.

PMID- 7647180
TI  - Biocybernetic system evaluates indices of operator engagement in automated task.
AB  - A biocybernetic system has been developed as a method to evaluate automated
      flight deck concepts for compatibility with human capabilities. A biocybernetic
      loop is formed by adjusting the mode of operation of a task set (e.g.,
      manual/automated mix) based on electroencephalographic (EEG) signals reflecting
      an operator's engagement in the task set. A critical issue for the loop operation
      is the selection of features of the EEG to provide an index of engagement upon
      which to base decisions to adjust task mode. Subjects were run in the closed-loop
      feedback configuration under four candidate and three experimental control
      definitions of an engagement index. The temporal patterning of system mode
      switching was observed for both positive and negative feedback of the index. The
      indices were judged on the basis of their relative strength in exhibiting
      expected feedback control system phenomena (stable operation under negative
      feedback and unstable operation under positive feedback). Of the candidate
      indices evaluated in this study, an index constructed according to the formula,
      beta power/(alpha power + theta power), reflected task engagement best.

PMID- 7647181
TI  - Assessing the impact of stressors on performance: observations on levels of
      analyses.
AB  - Applied researchers often are required to rely on limited laboratory studies to
      estimate the effects of various stressors on actual job performance. It can be
      difficult to select measures which lend themselves to implementation in
      laboratory settings while also providing sufficient capability to predict complex
      'real-world' performance. Studies which employ simulations of operationally
      relevant tasks and those which include the administration of basic cognitive
      tests are favored by many applications-oriented researchers. This is despite the
      fact that such a testing approach may limit sensitivity due to the requirements
      for extensive practice on these tasks in order to obtain stable results. Studies
      which use physiological assessments appear to be less readily accepted by applied
      researchers because of the difficulties in drawing a direct link between
      physiological indexes and operational performance. However, there are arguments
      to be made for the inclusion of physiological evaluations with the more
      traditional, performance-based measures. Data from three studies are cited here
      to support the value of using a multifaceted approach to the study of
      operationally-relevant stressors. Although these studies were not conducted to
      systematically investigate the relative merits of performance, cognitive, and
      physiological assessments, they do serve to highlight the fact that inclusion of
      all three types of tests tend to maximize the validity, interpretability, and
      sensitivity of applied research.

PMID- 7647182
TI  - Batch processing of 10,000 h of truck driver EEG data.
AB  - This paper describes the methods used to acquire and reduce a massive amount of
      EEG data (Wylie et al., 1990). The description is introduced by a review of a
      previous effort (Mackie and Miller, 1978). The earlier effort created much of the
      design philosophy for the second effort. The majority of data in the Paradox
      database came from 400 trips contributed by 80 commercial drivers driving both
      day and night revenue-cargo runs of 10 or 13 h each. The sleep and driving EEG
      data were collected with ambulatory Medilog recorders. Breathing and
      oxyhemoglobin measures were collected during sleep for sleep-apnea
      determinations. The sleep and driving-EEG data were placed in raw digitized files
      (128 samples/second), with the latter also available as compressed-band arrays
      for 20-s epochs, with associated Rechtschaffen and Kales (1968) manual scoring by
      polysomnographers for all EEG data. Sleep EEG, subjective driving performance and
      discrete-task data were also placed in the database, integrated and time
      registered to within 1-s accuracy with the driving EEG data. Each truck was
      extensively instrumented for lateral lane position, steering wheel position,
      speed, video image of the roadway, and video image of the face. Each driver
      recorded body temperatures several times per day, provided Stanford Sleepiness
      Scale readings several times each day, and was connected to the Vagal Tone
      Monitor while driving. In addition, driving segments were prefaced and followed
      by the performance of the Critical Tracking Task, the Psychomotor Vigilance Task,
      and the Code Substitution Task. The database should serve as an international
      resource from which many investigators may draw data.

PMID- 7647183
TI  - Psychophysiological measures applied to operational test and evaluation.
AB  - Psychophysiological measures have the potential to supplement and eventually
      replace subjective measures in determining fatigue and workload in military and
      commercial systems during test and evaluation. With the advances in equipment
      (such as miniaturization) over the last decade, the use of various
      psychophysiological methods, particularly electroencephalography (EEG), has
      become more feasible in operational settings. Accompanying this capability is the
      necessity to develop valid methodology and ensure consistent results within
      individuals and similar situations using relatively automatic analysis and
      presenting the results in non-specialist terms. This paper reviews the rationale
      for using psychophysiological metrics, particularly EEG, during the test and
      evaluation process, and discusses the requirements for its use and acceptance by
      decision-makers and subjects. The comments in this paper are based on 14 years of
      observation.

PMID- 7647184
TI  - Virtually-augmented interfaces for tactical aircraft.
AB  - The term Fusion Interface is defined as a class of interface which integrally
      incorporates both virtual and non-virtual concepts and devices across the visual,
      auditory and haptic sensory modalities. A fusion interface is a multi-sensory
      virtually-augmented synthetic environment. A new facility has been developed
      within the Human Engineering Division of the Armstrong Laboratory dedicated to
      exploratory development of fusion-interface concepts. One of the virtual concepts
      to be investigated in the Fusion Interfaces for Tactical Environments facility
      (FITE) is the application of EEG and other physiological measures for virtual
      control of functions within the flight environment. FITE is a specialized flight
      simulator which allows efficient concept development through the use of rapid
      prototyping followed by direct experience of new fusion concepts. The FITE
      facility also supports evaluation of fusion concepts by operational fighter
      pilots in a high fidelity simulated air combat environment. The facility was
      utilized by a multi-disciplinary team composed of operational pilots, human
      factors engineers, electronics engineers, computer scientists, and experimental
      psychologists to prototype and evaluate the first multi-sensory, virtually
      augmented cockpit. The cockpit employed LCD-based head-down displays, a helmet
      mounted display, three-dimensionally localized audio displays, and a haptic
      display. This paper will endeavor to describe the FITE facility architecture,
      some of the characteristics of the FITE virtual display and control devices, and
      the potential application of EEG and other physiological measures within the FITE
      facility.

PMID- 7647185
TI  - Cognitive task classification based upon topographic EEG data.
AB  - EEG from 19 electrodes was used to classify which of 14 tasks each of seven
      subjects had performed. Stepwise discriminant analysis (SWDA) was used to
      classify the tasks based upon training on one half of the spectrally analyzed 1
      min of data. Eighty six percent correct classification was achieved using
      principle components analysis (PCA) to determine the EEG bands to be used by the
      SWDA. Other approaches to deriving the EEG bands met with lower levels of
      success. The results indicate that frequency and topographical information about
      the EEG provides useful knowledge with regard to the nature of cognitive
      activity. Higher frequencies provided much of the information used by the
      classifier. The utility of this approach is discussed with regard to evaluating
      operator state in the work environment.

PMID- 7647186
TI  - Event-related potentials as indices of display-monitoring performance.
AB  - We evaluated event-related potentials (ERP) as indices of performance in three
      visual display-monitoring tasks: (a) signal detection, (b) running memory and (c)
      computation. Using factor analysis, we developed a global measure of performance
      (PFI) for each task. Task-relevant and irrelevant-probe stimuli elicited ERPs,
      which included components P1, N1, P2, P300, slow waves, and fronto-central
      negativities. In tasks (a) and (b), P300 amplitude in the task-relevant ERPs
      increased when the task was engaged, and was greater for accurate-than for
      inaccurate-response trials. In tasks (a) and (c), the irrelevant-probe ERPs also
      differed among task and performance conditions. To relate ERP measures to PF1, we
      developed linear regression models distinguished by three factors: general versus
      individual-subject, stimulus relevance, and signal-to-noise ratio (SNR). Model
      accuracy and reliability were highest for individual-subject, relevant-stimulus
      and high-SNR models, where average R2 values for the three tasks were 0.44, 0.46,
      and 0.38, respectively. We discuss implications of the models for performance
      monitoring and implications of the ERP effects for human information processing.

PMID- 7647187
TI  - Effects of attention and time-pressure on P300 subcomponents and implications for
      mental workload research.
AB  - Our approach to objective measures of mental workload is establishing
      relationships between components of the event-related brain potential (ERP) and
      information processing stages. These relationships can be used to infer the
      influence of specific workload conditions on specific processing stages. We
      recently showed that the ERP component P300 in choice tasks is composed of two
      subcomponents, P-SR and P-CR, which are time-related to stimulus-evaluation and
      response-selection. With these relations we could specify which processing stages
      were affected when certain workload conditions are varied. When attention was
      divided between the visual and auditory modalities compared to (unimodal) focused
      attention, the choice reaction time (RT) was prolonged, primarily in the auditory
      modality. This delay was mainly reflected in the P-CR latency, which shows that
      the division of attention mainly impairs the response-selection process in the
      auditory modality due to a bias of attention towards the visual modality. When
      the time-pressure was increased, the latency of the P-CR (and not of the P-SR)
      was shortened, but less than the choice RT. This suggests a (limited)
      acceleration of response-selection but not of stimulus evaluation. Since the
      response-selection process was accelerated less than the overt choice RT, an
      increase of the error rate was consequently observed. In summary we showed that
      increases of mental workload can induce accelerations or decelerations of
      specific processing stages which can be monitored by observing latency changes of
      the affiliated ERP components.

PMID- 7647189
TI  - 28th Annual meeting of the Society for the Study of Reproduction. Davis,
      California, July 9-12, 1995. Abstracts.

PMID- 7647188
TI  - Assessment of mental workload with task-irrelevant auditory probes.
AB  - A study was performed to examine the utility of an ERP-based irrelevant probe
      technique for the assessment of variations in mental workload. Ten highly trained
      Navy radar operators performed a simulated radar-monitoring task which varied in
      the density and type of targets to be detected and identified. This task was
      performed in the presence of a series of irrelevant auditory probes which the
      radar operators were instructed to ignore. Prior to performing the radar
      monitoring task the subjects performed a block of auditory detection trials in
      which they were asked to respond to the occurrence of one of two low probability
      tones and ignore the other low probability tone along with a higher probability
      standard tone. ERPs were recorded from the occurrence of the tones in both the
      baseline and low and high workload radar-monitoring conditions. The amplitude of
      the N100, N200, and early and late mismatch negativity (MMN) components decreased
      from the baseline to the low load radar-monitoring task and again with an
      increase in the difficulty of the radar-monitoring task. P300 amplitude was
      sensitive only to the introduction of the radar-monitoring task. These results
      are interpreted with respect to the phenomenon of attentional capture and suggest
      that the ERP-based irrelevant-probe technique might prove an effective method for
      the nonintrusive evaluation of increases in mental workload in complex tasks.

PMID- 7647190
TI  - [Common health disorders: self-care and self-medication].
AB  - SETTING: Community level. "Santa Maria de Benquerencia" Health District, Toledo.
      PARTICIPANTS: People over 15, chosen by random sampling from the municipal
      census, who stated that they had suffered some health disorder over the previous
      fortnight. MEASUREMENTS AND MAIN RESULTS: 212 surveys were accepted as valid
      (average age 42.75, 51.89% male and 48.11% female). 73% had suffered one of the
      disorders included in the survey during the previous fortnight. The commonest
      response was self-medication (39.84%), especially when dealing with pain and
      Pyrosis. Pyrazolones and Salicylates were the most commonly used drugs. The
      instructions were only read in 48.64% of cases. No measure was adopted in 34.56%
      of the disorders. The doctor was only consulted in 6.86% of cases. Both these
      responses were more common in men and young people. Non-pharmacological self-care
      was adopted in 30.07% of cases. This was generally of a dietetic or physical
      nature and was commoner in women and elderly people. CONCLUSIONS: Self-care,
      whether pharmacological or not, is the most common response to the perception of
      some symptom. These practices (especially self-medication because of its possible
      attendant problems) should be directed and used as one tool more in health care.

PMID- 7647191
TI  - [Identification and recording of risk factors both at reformed and non-reformed
      primary care centers].
AB  - OBJECTIVE: To identify factors associated with carrying out preventive activities
      in primary care. DESIGN: A crossover study through a self-administered
      questionnaire. SETTING: Reformed and non-reformed centres of the primary care sub
      division of the Barcelona Health Region, Catalan Health Institute. PARTICIPANTS:
      134 doctors from reformed centres (primary care teams) and 138 from non-reformed
      primary care centres (PCC). MEASUREMENTS AND MAIN RESULTS: Doctors from the
      reformed centres used records to a much greater extent (75.3% as against 26.3%
      for tobacco consumption; 76.2% as against 27.9% for alcohol consumption).
      Together with the type of centre, some professional characteristics were linked
      to the likelihood of carrying out preventive activities. These included, in
      particular, professionals' high valuation of their own effectiveness and
      professional practices such as the habitual use of a safety belt and anti-flu
      injections. CONCLUSIONS: In the reformed centres preventive activities are much
      more integrated. To optimise their use other important aspects, such as training
      in skills and improving professionals' perception of their own effectiveness,
      will have to be considered.

PMID- 7647192
TI  - [Evaluation of professional competence: are the times changing?].

PMID- 7647193
TI  - [Relationship between the physician's profile and transient work incapacity of
      his patients].
AB  - OBJECTIVE: To discover the relation between doctor's profile and his patient's
      unfitness for work. DESIGN: This was an observational crossover study. SETTING:
      Regional health authorities of Sant Feliu (Barcelona). PARTICIPANTS: 30 general
      practitioners throughout the whole of 1992. MEASUREMENTS AND MAIN RESULTS:
      Temporary doctors concede significance less unfitness for work (p = 0.002), and
      less unfitness motivated by flu (p = 0.028) than the others. Doctors belonging to
      the morning shift concede more upper respiratory infectious process (p = 0.03)
      than doctors belonging to the afternoon shift. Younger doctors and those
      specialised in family practice concede less unfitness for work motivated by flu
      than the others (p = 0.020) and (p = 0.019) respectively. CONCLUSIONS: The
      doctor's stability of work is the most influential factor analysed of the
      unfitness for work of his patients.

PMID- 7647194
TI  - [Evaluation of the impact of a care program for asthmatic children on the quality
      of anti-asthma drug prescriptions].
AB  - OBJECTIVE: To determine the influence of a programme of care for asthmatic
      children (CAC) on the quality of prescription of anti-asthmatic drugs. DESIGN: A
      controlled non-random intervention study. SETTING: Paediatric clinics operating
      before 1991 in Health Districts (HD) of Hospitalet. PARTICIPANTS: INTERVENTION
      GROUP: All the paediatricians ranked in the HD where the programme was set up (n
      = 3). CONTROL GROUP: All the paediatricians ranked in the rest of the HD (n = 9).
      INTERVENTION: In april 1992 the CAC programme, which included a pharmaco
      therapeutic procedure, was set up in the HD. MEASUREMENTS AND MAIN RESULTS:
      Prescriptions were evaluated by looking at the billing data of the Catalan Health
      Service between january and april, 1991, 1992 and 1993. The following Quality
      Indicators were evaluated: 1. Percentage of dosage of beta 2 adrenergics inhaled
      as against the total of beta 2 (oral and inhaled). 2. Percentage of DHD of
      Nedocromil (NC) and Cromoglycate (CG) as against the total of preventive drugs
      (NC + CG + Ketotifen). 3. Number of packages of oral and/or rectal Theophyllines,
      counter-indicated combinations and anti-inflammatory drugs (Chromones and inhaled
      steroids). CONCLUSION: The influence of the programme can be considered very
      positive, since an increase in all the quality indicators of the prescription of
      anti-asthmatics was observed, something that did not occur in the Control Group.

PMID- 7647195
TI  - [School acceptance of the theater as a method of health education].
AB  - OBJECTIVE: To find how theatre was evaluated as an instrument of Health Education
      by the pupil-actors of a school where a play on the European Code against Cancer
      was put on. DESIGN: An observational study (descriptive and crossover). SETTING:
      Community level. Primary Education. PARTICIPANTS: 100 pupil-actors of the 220 at
      a primary school in a rural area. They were selected by means of a free,
      voluntary and spontaneous practical theatre test. INTERVENTIONS: A theatrical
      show with 14 scenes was created. 8 performances, open to the public, were held in
      the village's Cultural Centre. MEASUREMENTS AND MAIN RESULTS: Evaluation was with
      a self-administered questionnaire composed for the occasion and consisting of
      closed multiple-choice questions. An anonymous group survey, done in class and
      covering each year separately, included 77 of the 100 actors. A prior pilot
      survey had evaluated intelligibility. The results were that 97.4% classed the
      experience as positive and 87% of them considered it very good. 81% had no
      problem at the moment of acting. 83% were helped by teachers and 81% by parents.
      98% would like to do theatre again. CONCLUSIONS: Theatre is highly rated and
      widely accepted by children, making it a useful

PMID- 7647196
TI  - [Tobacco: risk factor in a health district].
AB  - OBJECTIVE: To find the prevalence of tobacco dependency in our community and to
      identify tobacco consumption in our chronic patients. DESIGN: A crossover study.
      A descriptive analysis of the data. SETTING: A Health District. Mixed population,
      both urban and rural. PARTICIPANTS: A Health Survey which included 1,071
      individuals (95% Confidence and 3% precision), selected by means of simple random
      sampling from the Municipal Census. MEASUREMENTS AND MAIN RESULTS: A 32.3%
      prevalence of tobacco dependency, greater among men (50.7%) than women (15.7%).
      Among the young, there is a marked tendency for the number of smokers to level
      out between the sexes. 15.6% of smokers consume more than 24 cigarettes per day.
      Between 15 and 20% of patients suffering hypertension, diabetes,
      hypercholesterolaemia and the effects of ischaemic cardiopathy, along with 25% of
      those who had suffered a CVA and almost 40% of chronic bronchitics, continue to
      smoke. CONCLUSIONS: Advice against smoking must be directed towards younger and
      younger age groups, including both men and women. The high prevalence of people
      still smoking among the chronically ill should cause us to reflect on our advice
      against tobacco to such patients.

PMID- 7647197
TI  - [A new cause for primary care consultation: nocturnal snoring].

PMID- 7647198
TI  - [Professional profile of the family physician. Work Group of the Spanish Society
      of Family and Community Medicine].

PMID- 7647199
TI  - [Services without programs: just round the corner].

PMID- 7647200
TI  - [Mild organophosphate poisoning: a lesser evil?].

PMID- 7647202
TI  - [A descriptive study of the use of thyroid function tests (TFT) at a health
      center].

PMID- 7647201
TI  - [Reflex sympathetic dystrophy: not always post-traumatic].

PMID- 7647203
TI  - [Tetanus vaccination in adults: the situation in primary care].
AB  - OBJECTIVE: To describe the strategies adopted to increase anti-tetanus
      vaccination coverage in people over 24, as well as the record systems which exist
      in Castilla-La Mancha health centres. In addition, to determine those factors
      involved in achieving greater coverage which depend on the primary care team
      (PCT). DESIGN: An observational study of a crossover type. SETTING: Primary care.
      PARTICIPANTS: The PCT in Castilla-La Mancha existing in 1993. 72.5% reply rate.
      MEASUREMENTS AND MAIN RESULTS: The average coverage achieved, weighted according
      to population, was 10.55%. The main risk groups in which strategies to increase
      coverage were put into practice were: the chronically ill (49.5%), professionals
      at risk (37.6%) and pregnant women (32.6%). Patients were summoned for follow-up
      doses by 41.3% of PCTs as a matter of habit and by 41.3% occasionally. Normally
      the vaccination was recorded in the Medical Notes by 41.9% of PCTs. A linear
      tendency between a higher vaccination rate and, on the other hand, both greater
      insistence that patients attend for revaccination (p = 0.01) and better recording
      in the medical notes (p = 0.04) was confirmed. Vaccination coverage was
      significantly greater in health centres where less people were seen (p < 0.001)
      and which were more modern (p = 0.003). CONCLUSIONS: The low anti-tetanus
      vaccination coverage found justifies setting up initiatives of demonstrated
      efficacy to increase anti-tetanus immunisation. Better records and insistence on
      patients' attendance for follow-up doses are factors linked to greater
      vaccination coverage.

PMID- 7647204
TI  - [Continuing education of the primary care team].

PMID- 7647205
TI  - [The demand for medical consultations in primary health care in Navarre].
AB  - OBJECTIVE: To find the utilization of the health center medical services in
      Navarra and how it relates to characteristics of both doctors and population.
      DESIGN: Descriptive study. SETTING: Primary Health Care. PARTICIPANTS: 167 family
      doctors (GP) from 31 PCTs. The daily on-demand, administrative and pre-programmed
      consultation in the records of the PCTs from 1/5/90 to 30/3/91 were analysed for
      each doctor. MEASUREMENTS AND RESULTS: Indicators: frequentation
      (interviews/inhabitant/year), pressure of attendance (interviews/doctor/day),
      programmed pressure (pre-programmed interviews/doctor/day) and administrative
      pressure (administrative interviews/doctor/day). Average frequency in Navarra is
      5.26 (SD = 2.58); average pressure of attendance, 32.13 (SD = 11.88); average pre
      programmed pressure, 2.68 (SD = 1.81) and average administrative pressure, 7.9
      (SD = 7.11). Frequency is inversely determined by the size of the allotted
      population list (p < 0.01). On studying doctors with an allotted list of _ 1,500
      people, GPs with residential training have lower frequency of interviews than the
      rest (p < 0.01), whereas rural GPs have higher frequency and higher pressure of
      attendance (p < 0.001). Rural areas in the North of Navarra have a lower
      frequency of interviews and pressure of attendance than rural areas in the South
      (p < 0.02). CONCLUSION: Values of frequency in Navarra are comparable with other
      countries.

PMID- 7647206
TI  - [Factors relating to the cost and quality of drug prescriptions in primary care].
AB  - OBJECTIVES: To analyse, quantitatively and qualitatively, the pharmaceuticals
      prescribed by doctors within two models of Primary Care: the reformed (RM) and
      non-reformed (NRM). To study which variables of the doctor, work-centre or
      community attended explain prescription variations. DESIGN: An observational
      crossover study. SETTING: Primary Health Care centres in the province of Malaga.
      PARTICIPANTS: The prescriptions of 454 doctors were studied: 259 RM and 195 NRM.
      A univariant analysis was performed on the indicators of prescription of both
      health-care models, with afterwards a multiple linear regression analysis to
      study the effect of the rest of the variables. RESULTS: There were differences in
      two of the quantitative indicators studied, with more prescriptions and expense
      per insured person per day in the NRM, as well as higher prescription for several
      therapeutic groups, mainly of drugs against flu, and also of drugs against
      infections, tonics, restoratives and capillary protectors. The variables which
      best explained prescriptions in the multivariant analysis were: consultations per
      insured person per day and the percentage of pensioners on the doctor's list.
      CONCLUSIONS: We thought that the differences between the two health-care models
      in the quantitative analysis were of very little relevance. They were greater in
      the qualitative one and suggested higher quality of prescription in the RM.
      Pressure of numbers was identified as, among the studied variables, that which
      best explains prescription, over and above others like the health-care model or
      medical training. As for the percentage of pensioners on the doctor's list, it
      should be borne in mind at the hour of evaluating his/her prescriptions.

PMID- 7647207
TI  - [Use of ticlopidine in primary care].
AB  - OBJECTIVES: To find the reasons for prescription of Ticlopidine, which acts
      against the aggregation of platelets and is catalogued as "with hospital
      diagnosis", and to evaluate the criteria for its correct use and whether it is
      actually used in Spain to treat authorised symptoms. DESIGN: A descriptive,
      crossover and retrospective study. SETTING: Primary Care districts in the
      catchment area of the Virgen del Rocio hospital in Sevilla. PATIENTS: Those who
      requested permits for Ticlopidine prescriptions, documented by the clinical
      report. MEASUREMENTS AND MAIN RESULTS: The following data were recorded from the
      clinical reports presented when the Ticlopidine prescription permits were
      requested: patient's identification, diagnosis, pharmaceutical speciality,
      dosage, length of treatment and recommendation of haematological check-ups. Out
      of 407 reports available, the diagnosis corresponded to one of the authorised
      symptoms in 50.6% of cases. In a third of the patients the recommended dose was
      half that endorsed by the published clinical trials. Only in 2.7% of cases was
      mention made of the desirability of having haematological check-ups to forestall
      possible adverse reactions. The possibility of a counter-indication to
      Acetylsalicylic acid was only rarely mentioned. CONCLUSIONS: Ticlopidine is
      recommended in 50% of cases for symptoms for which it is not authorised in our
      country: moreover, in 35% of cases, at doses lower than those established as
      effective. The information given by the doctor who initiates the treatment is
      usually insufficient. There is a need to reassess whether cataloguing a medicine
      as "with hospital diagnosis" aids its rational use.

PMID- 7647208
TI  - [Cost accountability in primary care: list of services].
AB  - OBJECTIVE: To find the costs of the products in the set of offered services and
      the costs of Primary Care Centre services, using the costs of functioning.
      DESIGN: Descriptive study. SETTING: Primary Care Centres. PARTICIPANTS: Seven
      Primary Care Centres managed by the Catalan Institute of Health. MEASUREMENTS AND
      MAIN RESULTS: The costs of chapters I (staff) and II (running costs) from the
      budget accounting of the 1993 exercise. The average costs per product of
      unplanned attendance on the general practitioner (768 pesetas) and paediatrician
      (1,152 pesetas) are lower than for general medical (3,291 pes) or paediatric
      (5,303) nursing. The cost of paediatrics is higher than general medicine for any
      type of medical attendance. Average costs for unplanned attendance at the
      odontologist (3,804 pes) and social worker (10,661 pes) are higher than for other
      professionals. Services with cost per inhabitant are, in order of precedence:
      paediatrics (13,343 pesetas/inhabitant), general medicine (6,401), odontology
      (811) and social work (292). CONCLUSIONS: The analysis of costs of products and
      services allows us to know and compare findings for different health providers.

PMID- 7647209
TI  - [Silent thyroiditis and postpartum thyroiditis].
AB  - OBJECTIVE: Six cases of silent thyroiditis are described. Clinical, analytical,
      therapeutical and prognostical features are reviewed. DESIGN: Descriptive and
      retrospective study. SETTING: Outpatient endocrinological clinic of a General
      Hospital PATIENTS OR OTHER PARTICIPANTS: Six women (age 26-41 years) that fulfil
      clinical and analytical criteria of silent thyroiditis. In 4 patients thyroiditis
      was diagnosed in the postpartum period and in the remaining 2 there was no
      relationship with pregnancy. MAIN MEASUREMENTS AND RESULTS: Serum levels of
      thyroid hormones and thyroglobulin and thyroid peroxidase antibodies were
      measured in all patients. Follow-up period was between 12 and 41 months. The 2
      patients with the sporadic form of silent thyroiditis showed clinical and
      analytical data of thyrotoxicosis that spontaneously resolved. The remaining 4
      patients presented with hypothyroidism. In one of them the hypothyroidism
      spontaneously resolved, in 2 it became permanent and in a further one it
      developed to subclinical hypothyroidism. CONCLUSIONS: Silent thyroiditis
      (sporadic or postpartum) is a frequent disorder, usually benign and transient. It
      can present in different clinic forms and evolve to resolution of permanent
      thyroid dysfunction.

PMID- 7647210
TI  - [Seroprevalence of Toxoplasma gondii in pregnant women].
AB  - OBJECTIVES: To find the seroprevalence of Toxoplasma gondii in pregnant women and
      identify associated factors. To assess the relevance of systematic screening of
      pregnant women. DESIGN: A descriptive crossover study of prevalence. SETTING:
      Primary Care in the "Puerto de la Torre" district of Malaga. PATIENTS: Pregnant
      women who gave birth in 1993 and were included in the Pregnancy Control
      Programme. 191 cases were studied. INTERVENTIONS: A qualitative detection of
      specific IgG by means of indirect EIA. Every woman with antibodies was considered
      seropositive, irrespective of the title. Clinical records were the source of
      data. RESULTS: Average age was 27.13. Seroprevalence (IgG+) was 25.7%. Crude
      analysis of association between IgG+y was: previous abortions, OR 5.28, C.I. 95%
      (2.24-12.30), P = 0.00009; domestic animals, OR 1.76, CI (0.74-4.13), P = 0.08;
      low economic status, OR 1.9, CI (1.04-3.4), P = 0.057; had given birth before, OR
      1.5, CI (0.81-2.74), P = 0.23. The multivariant analysis for IgG+dependent
      variable was: for previous abortions, OR 3.81, P = 0.005; low status OR 2.13, P =
      0.04; domestic animals OR 1.71, P = 0.13, independent of age. There were no
      interactions. CONCLUSIONS: There was low seroprevalence in comparison with the
      national average. Low economic status and previous abortions suppose the highest
      risks of IgG+. Screening is recommended.

PMID- 7647211
TI  - [Tuberculin test in diabetic patients in a health center].
AB  - OBJECTIVES: To determine the frequency of Tuberculin positives in the diabetic
      population attending our Health Centre, with readings at three and seven days. Of
      less importance, to assess how often patients present conversion after a second
      Tuberculin test, seven days after the first; and to determine the frequency of
      Tuberculin positives in diabetics in relation to whether they are over or under
      65. DESIGN: A transversal observational study. SETTING: Pio XII Health Centre,
      Ciudad Real. PARTICIPANTS: Patients registered as diabetic in the eight General
      Medicine clinics and who attended for the customary check-ups. MEASUREMENTS AND
      RESULTS: PPD was administered to 163 diabetics and the test was read at three and
      seven days; if this last reading was negative, a second test was carried out and
      evaluated at three days. At three days 42.2% were positive; at seven, there was
      an increase of 6.5% of the total. A second test was performed on 78 patients,
      which provided an increase in patients with tuberculous infection of 7.14% of the
      total. There was a statistically significant relationship (p < 0.001) between the
      positive responses of the first Mantoux and age. CONCLUSIONS: There is a high
      prevalence of Tuberculin positive patients, which increases when another reading
      is done seven days after the Mantoux; as it does after a second test, by which a
      retreat in these patients' response to Tuberculin was observed.

PMID- 7647212
TI  - [Acne vulgaris in adolescence].

PMID- 7647213
TI  - [Primary health care and research units].

PMID- 7647214
TI  - [Measurement of functional capacity].

PMID- 7647215
TI  - [Treatment or patients under long term care?].

PMID- 7647216
TI  - Tissue factor interactions with factor VII: measurement and clinical significance
      of factor VIIa in plasma.
AB  - Certain epidemiological studies have implicated elevated factor VII coagulant
      activity as a risk factor for ischaemia heart disease. However, progress in
      understanding the clinical significance of elevated plasma factor VII levels has
      been hampered by: (1) differences between laboratories in the methodology for
      measuring factor VII; (2) the existence of multiple forms of factor VII in plasma
      (i.e. factor VIIa, zymogen factor VII, and a possible phospholipase-sensitive
      form of factor VII); (3) the resulting uncertainty regarding what is actually
      being measured in factor VII coagulant assays. Recent mutagenesis studies of
      tissue factor (the obligate protein cofactor for factor VIIa) have led to new
      assay technologies capable of quantifying trace levels of plasma factor VIIa
      without interference from zymogen factor VII. This review article focuses on the
      current status of measurement of plasma factor VII/VIIa levels and the
      relationship between various plasma forms of factor VII and risk of thrombotic
      disease.

PMID- 7647217
TI  - Tissue factor expression in endothelial cells in health and disease.
AB  - Plasma tissue factor (TF) antigen can be detected in healthy volunteers and may
      be significantly increased in patients with disseminated intravascular
      coagulation (DIC). Plasma TF antigen level in patients with DIC was significantly
      reduced after therapy. The TF activity of human umbilical vein endothelial cells
      (HUVEC) cultured with lipopolysaccharide (LPS), cytokines and the medium of
      cultured mononuclear cells (MNC) was significantly increased. TF expression was
      induced in HUVEC and MNC by incubation with lipoproteins, suggesting that
      hyperlipidaemia is a direct risk factor in thrombotic disease. TF activity in
      HUVEC was significantly increased in the presence of plasma and this activation
      was higher in patients with thrombotic thrombocytopenic purpura (TTP) and DIC.
      Enhanced TF production by endothelial cells may be important in the pathogenesis
      of thrombotic diseases.

PMID- 7647219
TI  - The clinical value of tissue factor assays.
AB  - Tissue factor (TF) is now considered to be the primary physiologic activator of
      the blood coagulation system. Coupled with recent advances in our understanding
      of the biochemistry of TF this has heightened interest in measuring aspects of TF
      activity in disease states. Expression of TF by blood monocytes in various
      diseases is an established trigger for intravascular coagulation and there is now
      a considerable body of experience with its measurement. This has considerable
      clinical potential although more widespread application awaits a consensus on the
      most appropriate methodologic approach to its measurement. TF can be detected in
      urine and may reflect the activation state of renal macrophages. Urinary TF is
      increased in cancer and could have diagnostic and prognostic value in a variety
      of malignant diseases. Finally, it is now possible to measure soluble TF in
      plasma. One such assay is commercially available and is technically simple to
      perform. The clinical value of such assays, however, must await better
      understanding of the source and function of soluble TF in plasma.

PMID- 7647218
TI  - Tissue factor antigen levels in various biological fluids.
AB  - Tissue factor (TF), a transmembrane surface protein, is known to initiate
      thrombogenesis through plasmatic and cellular activation processes. Besides
      complexing with factor VII, eventually leading to fibrin generation via the
      extrinsic pathway, TF can also activate factor IX, resulting in the intrinsic
      activation of coagulation. Other functions of TF are currently unknown, although
      various cells are believed to have TF receptors. Many of the post-surgical and
      post-interventional thrombotic events are due to the release of TF. Increased
      levels of TF are associated with several pathologic conditions such as cancer,
      sepsis and inflammation. Cellular necrosis also results in an increase of TF as
      the cells in the traumatized area lyse and release endogenous cell surface-bound
      TF. An ELISA method (American Diagnostica, Greenwich, CT) has been developed to
      assay TF antigen levels in various biological fluids. This ELISA employs a murine
      monoclonal antibody raised against native human TF for antigen capture. In this
      study, cerebrospinal fluid, peritoneal fluid, pleural effusion and urine from
      patients were assayed for their TF content using this ELISA method. Normal
      individual serum and plasma were also assayed as controls against which the
      levels of TF in the patients' body fluids could be compared. The amount of TF
      antigen in normal human plasma and serum was 165 +/- 139 pg/ml and 165 +/- 110
      pg/ml, respectively. Concentrations of TF antigen in other fluids were:
      cerebrospinal fluid 868 +/- 721 pg/ml, peritoneal fluid 124 +/- 247 pg/ml,
      pleural effusion 385 +/- 569 pg/ml, synovial fluid 97 +/- 23 pg/ml, seminal
      plasma 11,485 +/- 875 pg/ml and urine 86 +/- 57 pg/ml.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7647221
TI  - Tissue factor/tissue factor pathway inhibitor.

PMID- 7647220
TI  - Relative roles of tissue factor pathway inhibitor and antithrombin in the control
      of thrombogenesis.
AB  - Tissue factor pathway inhibitor (TFPI) controls activation of blood coagulation
      while antithrombin (AT) regulates the final stage. Both inhibitors inhibit the
      intermediate stage of activation. Subnormal levels of TFPI increase the risk of
      disseminated intravascular coagulation (DIC) in septic conditions, and the risk
      of occlusive thrombi over damaged vascular intima or fissured arteriosclerotic
      plaques. The risk of venous thrombosis is increased by subnormal AT or subnormal
      activity of the protein C system. In contrast, TFPI may be little involved in the
      control of deep venous thrombosis. Heparin strongly accelerates AT and releases
      TFPI to the blood. Both these effects may contribute to the antithrombotic effect
      of heparin. In septic DIC, heparin may contribute little to quench activation of
      coagulation. Once hereditary deficiency of TFPI is described, its biological role
      will be better understood.

PMID- 7647222
TI  - Tissue factor pathway inhibitor: proposed heparin recognition region.
AB  - After intravenous and subcutaneous injection, heparins and low-molecular-weight
      heparins release tissue factor pathway inhibitor (TFPI) into the blood stream.
      Protamine immediately reverses the plasma levels of TFPI to pretreatment values.
      A low-molecular-weight dermatan sulphate releases only very small amounts of TFPI
      after intravenous injection without a clear dose-dependent effect. Together with
      other data from literature, it seems likely that TFPI is rather specifically
      released by acidic glycosaminoglycans. In the present paper a binding region for
      heparins is reported to be located in the C-terminal end. A basic amino acid
      cluster occurs between 256-lysine and 261-lysine. This proposed heparin
      recognition region in TFPI is similar to the recognition region in antithrombin
      III and other proteins. The binding between the basic region at the C-terminal
      end of TFPI and the negatively charged sulphate or carboxyl-groups of
      glycosaminoclycans may occur in a linear manner. A comparison of a helical wheel
      diagram of antithrombin III and tissue factor pathway inhibitor support also the
      proposal of this form of a heparin recognition region in TFPI. Further studies
      are now required to analyse these interactions.

PMID- 7647223
TI  - The role of tissue factor pathway inhibitor in the mediation of the
      antithrombotic actions of heparin and low-molecular-weight heparin.
AB  - It is widely accepted that antithrombin III (ATIII) mediated anti-Xa and anti-IIa
      effects are the sole determinant of the antithrombotic actions of unfractionated
      heparin (UFH) and low-molecular-weight heparins (LMWHs). However, there are
      several unexpected observations such as the greater than 100% bioavailability of
      subcutaneously administered LMWH as measured by a chromogenic based anti-Xa
      method. The authors have proposed that, besides ATIII mediated antiprotease
      actions, additional endogenous factors may be responsible for the observed
      therapeutic and prophylactic actions of heparins. With the identification of
      tissue factor pathway inhibitor (TFPI) some of the unexpected effects of heparins
      can now be clarified. To investigate the role of heparin-releasable TFPI on LMWHs
      the anti-Xa and TFPI antigen levels after prophylactic and therapeutic
      administration of UFH and LMWHs have been studied in defined clinical trials.
      Regardless of the dosage designation (mg/kg or units/kg) each LMWH followed a
      distinct TFPI release profile. Similarly, in the intravenous studies these LMWHs
      produced an instantaneous increase in the TFPI antigen level. The anti-Xa effects
      did not always follow the same pattern as the TFPI antigen levels. These data
      suggest that the anti-Xa potency of a given LMWH is not the sole determinant of
      the antithrombotic actions of heparin and LMWH. In addition to pharmacologic
      agents, the effect of sequential compression devices (SCD) on the release of TFPI
      was also studied. A two-fold increase in TFPI antigen levels was observed in
      normal volunteers undergoing long leg compression for 1 h.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7647224
TI  - Functional and immunologic methods for the measurement of human tissue factor
      pathway inhibitor.
AB  - Recent publications have addressed the topic of an important regulator of the
      extrinsic pathway, the tissue factor pathway inhibitor (TFPI). Tissue factor
      dependent reactions are regulated by TFPI, a member of a superfamily of proteins,
      homologous to aprotinin (Kunitz). An indirect assay has been developed to
      quantitate levels of TFPI in human plasma by measuring its ability to inhibit
      FVIIa-TF activity (Actichrome TFPI). A sandwich ELISA (Imubind Total TFPI), which
      recognizes all forms of TFPI (e.g. lipid associated, carboxytruncated TFPI, as
      well as recombinant and native TFPI) was used to compare antigenic and functional
      TFPI levels. The Actichrome TFPI kit exhibited no detectable response to other
      clotting factors tested, in their normal and pathologic ranges. Mean circulating
      levels of TFPI were 55 ng/ml and 61 ng/ml using the activity assay and the ELISA,
      respectively. The difference might be attributed to inactive forms of TFPI that
      are detected by the ELISA. Intra-assay and inter-assay variation (% CV) was less
      than 5% for three samples of known concentration were assayed in replicates of
      20. The total TFPI ELISA has a sensitivity of 0.3 ng/ml for serum and plasma
      samples, assayed at a 20-fold dilution. Specificities of both the capture and
      detection antibodies were confirmed via Western blot analysis visualizing bands
      at 34 kDa and 21 kDa, respectively, for full length and truncated TFPI. In
      conclusion, two assays which quantitate circulating levels of TFPI have been
      developed and optimized: the Actichrome TFPI Activity Assay and the Imubind Total
      TFPI ELISA.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7647225
TI  - Tissue factor pathway inhibitor and the current concept of blood coagulation.
AB  - Tissue factor pathway inhibitor (TFPI) is a multivalent, Kunitz-type plasma
      proteinase inhibitor that regulates tissue factor-induced coagulation. TFPI
      directly inhibits activated factor X and, in a factor Xa-dependent manner,
      produces feedback inhibition of the factor VIIa/tissue factor catalytic complex.
      The properties of this inhibitor help explain the clinical need for 'extrinsic'
      and 'intrinsic' coagulation pathways and have led to a reformulation of the
      coagulation cascade. In the revised hypothesis, factor VIIa/tissue factor is
      responsible for the initiation of coagulation but, owing to TFPI-mediated
      feedback inhibition, amplification of the procoagulant response though the
      actions of factor VIII, IX and XI is required for sustained haemostasis.

PMID- 7647226
TI  - Measurement of functional and immunologic levels of tissue factor pathway
      inhibitor. Some methodologic considerations.
AB  - Tissue factor pathway inhibitor (TFPI) is a newly identified inhibitor of
      proteases generated during activation processes. Several functional methods based
      on a chromogenic substrate technique measuring residual tissue
      thromboplastin/FVIIa catalytic activity using excess factor X and a chromogenic
      substrate for FXa have been published. Recently, a sandwich ELISA method has
      become available. A modified functional method was compared with the ELISA based
      antigen method in several groups of normal individuals. The functional assay is
      sensitive to TFPI concentrations of 125-200 ng/ml based on a rTFPI standard. The
      immunologic method is sensitive from 0 to 400 ng/ml. A marked dichotomy was
      observed between the two methods. The ratio between TFPI antigen and functional
      levels varies widely in patient groups. This TFPI standard was supplemented with
      buffer and normal human plasma and functional TFPI was measured before and after
      heat treatment at 56 degrees C for 10 min. Heat treatment of plasma (buffer)
      after the addition of TFPI resulted in decreased functional TFPI compared with
      the addition of TFPI after the plasma (buffer) was heat treated. In contrast, the
      immunologic method does not require heat treatment. Addition of exogenous TFPI to
      plasmas obtained from normal and the above patient plasmas demonstrated that
      recovery of functional TFPI activity was plasma dependent. Plasma proteins
      markedly influenced functional and antigenic levels of TFPI. The TFPI standard
      added to human pooled plasma gave varying recoveries in the immunologic and
      functional assays. These results indicate that currently available methods may
      provide highly variable results on TFPI levels. Several matrix related effects
      should be taken into account for proper evaluation of TFPI.

PMID- 7647227
TI  - Using the soft touch on cell surfaces.

PMID- 7647228
TI  - Burst busters: uncovering a new mechanism in pancreatic beta-cells.

PMID- 7647229
TI  - Engineering a domain-locking disulfide into a bacterial malate dehydrogenase
      produces a redox-sensitive enzyme.
AB  - Light-dependent reduction of cystine disulfide bonds results in activation of
      several of the enzymes of photosynthetic carbon metabolism within the
      chloroplast. We have modeled the tertiary structure of four of these light
      activated enzymes, namely NADP-linked malate dehydrogenase, glyceraldehyde-3-P
      dehydrogenase, fructosebisphosphatase, and sedoheptulosebisphosphatase, and
      identified cysteines in each enzyme that be expected to form inactivating
      disulfide bonds (Li, D., F. J. Stevens, M. Schiffer, and L. E. Anderson, 1994.
      Biophys. J. 67:29-35). We have now converted two residues in the Escherichia coli
      NAD-linked malate dehydrogenase to cysteines and produced a redox-sensitive
      enzyme. Oxidation of domain-locking cysteine residues in the mutant enzyme
      clearly mimics dark inactivation of the redox-sensitive chloroplast
      dehydrogenase. This result is completely consistent with our proposed mechanism.

PMID- 7647230
TI  - Deformation and flow of red blood cells in a synthetic lattice: evidence for an
      active cytoskeleton.
AB  - We introduce the use of microfabrication techniques to construct on a silicon
      wafer a synthetic capillary bed with 2.5- to 4-micron (mu)-wide channels.
      Establishment of a fluid pressure gradient allowed us to observe simultaneously
      using optical microscopy hundreds of cells flowing through the bed at
      physiological speeds. We find a large distribution of mobilities among red cells
      flowing through the structure; smaller channels provide a greater impedance to
      flow than larger ones, indicating that kinetic drag variations provide the origin
      of the distribution. The mobility of a particular cell is not correlated with the
      cell diameter but appears to be inversely correlated with intracellular calcium
      concentration of the cell, as determined by fluorescence of the calcium-binding
      dye fluo-3 AM. Also, we are able to use the parallel processing nature of our
      arrays to observe isolated events where the rigidity of the red cell seems to
      change suddenly over several orders of magnitude as it blocks a channel in the
      array.

PMID- 7647231
TI  - Electrostatic calculations of amino acid titration and electron transfer, Q-AQB-
      >QAQ-B, in the reaction center.
AB  - The titration of amino acids and the energetics of electron transfer from the
      primary electron acceptor (QA) to the secondary electron acceptor (QB) in the
      photosynthetic reaction center of Rhodobacter sphaeroides are calculated using a
      continuum electrostatic model. Strong electrostatic interactions between
      titrating sites give rise to complex titration curves. Glu L212 is calculated to
      have an anomalously broad titration curve, which explains the seemingly
      contradictory experimental results concerning its pKa. The electrostatic field
      following electron transfer shifts the average protonation of amino acids near
      the quinones. The pH dependence of the free energy between Q-AQB and QAQ-B
      calculated from these shifts is in good agreement with experiment. However, the
      calculated absolute free energy difference is in severe disagreement (by
      approximately 230 meV) with the observed experimental value, i.e., electron
      transfer from Q-A to QB is calculated to be unfavorable. The large stabilization
      energy of the Q-A state arises from the predominantly positively charged residues
      in the vicinity of QA in contrast to the predominantly negatively charged
      residues near QB. The discrepancy between calculated and experimental values for
      delta G(Q-AQB-->QAQ-B) points to limitations of the continuum electrostatic
      model. Inclusion of other contributions to the energetics (e.g., protein motion
      following quinone reduction) that may improve the agreement between theory and
      experiment are discussed.

PMID- 7647232
TI  - Transport effects on the kinetics of protein-surface binding.
AB  - A detailed model is presented for protein binding to active surfaces, with
      application to the binding of avidin molecules to a biotin-functionalized fiber
      optic sensor in experiments reported by S. Zhao and W. M. Reichert (American
      Chemical Society Symposium Series 493, 1992). Kinetic data for binding in
      solution are used to assign an intrinsic catalytic rate coefficient k to the
      biotin-avidin pair, deconvoluted from transport and electrostatic factors via
      application of coagulation theory. This intrinsic chemical constant is built into
      a reaction-diffusion analysis of surface binding where activity is restricted to
      localized sites (representing immobilized biotin molecules). The analysis leads
      to an effective catalytic rate coefficient keff characterizing the active
      surface. Thereafter, solution of the transport problem describing absorption of
      avidin molecules by the macroscopic sensor surface leads to predictions of the
      avidin flux, which are found to be in good agreement with the experimental data.
      The analysis suggests the following conclusions. 1) Translational diffusion
      limitations are negligible for avidin-biotin binding in solution owing to the
      small (kinetically limiting) value k = 0.00045 m/s. 2) The sparse distribution of
      biotin molecules and the presence of a repulsive hydration force produce an
      effective surface-average catalytic rate coefficient keff of order 10(-7) m/s,
      much smaller than k. 3) Avidin binding to the fiber optic sensor occurs in an
      intermediate regime where the rate is influenced by both kinetics and diffusion.

PMID- 7647233
TI  - Modeling the electrophoresis of rigid polyions: application to lysozyme.
AB  - An algorithm is developed to determine the electrophoretic mobility of a rigid
      polyion modeled as a low dielectric volume element of arbitrary shape containing
      an arbitrary charge distribution. The solvent is modeled as a high dielectric
      continuum with salt distributed according to the linearized Poisson Boltzmann
      equation. Account is also taken of a Stern layer that separates the molecular
      surface and the surface of hydrodynamic shear, or Stern surface. Relaxation of
      the ion atmosphere because of the presence of the external field is ignored. The
      electrostatic and hydrodynamic problems are both solved by boundary element
      methods. The procedure is first applied to spherical polyions containing
      monopolar, dipolar, and quadrupolar charge distributions, and calculated
      mobilities are found to be in excellent agreement with the theory of Yoon and
      Kim. It is then applied to lysozyme by using models that account for the detailed
      shape and charge distribution of the enzyme. For reasonable choices of the
      molecular and Stern surfaces, calculated and experimental mobilities are found to
      be in fair agreement with each other. However, if a pH independent Stern layer
      (or, equivalently, translational diffusion constant, Dt) is assumed, the
      calculated mobilities exhibit a stronger pH dependence than is observed
      experimentally. A small increase in Dt with increasing pH could correct this
      discrepancy.

PMID- 7647234
TI  - Primary structure and properties of helothermine, a peptide toxin that blocks
      ryanodine receptors.
AB  - Helothermine, a protein from the venom of the Mexican beaded lizard (Heloderma
      horridum horridum), was found to inhibit [3H]ryanodine binding to cardiac and
      skeletal sarcoplasmic reticulum, to block cardiac and skeletal ryanodine receptor
      channels incorporated into planar bilayers, and to block Ca(2+)-induced Ca2+
      release triggered by photolysis of nitr-5 in saponin-permeabilized trabeculae
      from rat ventricle. Cloning of the helothermine cDNA revealed that the protein is
      composed of 223 amino acids with a molecular mass of 25,376 daltons, and
      apparently is stabilized by eight disulfide bridges. The peptide sequence showed
      significant homology with a family of cysteine-rich secretory proteins found in
      the male genital tract and in salivary glands. The interaction of helothermine
      and ryanodine receptors should serve to define functional domains within the
      channel structure involved in the control of Ca2+ release from sarcoplasmic
      reticulum.

PMID- 7647235
TI  - Spatial distribution of cardiac transmembrane potentials around an extracellular
      electrode: dependence on fiber orientation.
AB  - Recent theoretical models of cardiac electrical stimulation or defibrillation
      predict a complex spatial pattern of transmembrane potential (Vm) around a
      stimulating electrode, resulting from the formation of virtual electrodes of
      reversed polarity. The pattern of membrane polarization has been attributed to
      the anisotropic structure of the tissue. To verify such model predictions
      experimentally, an optical technique using a fluorescent voltage-sensitive dye
      was used to map the spatial distribution of Vm around a 150-microns-radius
      extracellular unipolar electrode. An S1-S2 stimulation protocol was used, and vm
      was measured during an S2 pulse having an intensity equal to 10x the cathodal
      diastolic threshold of excitation. The recordings were obtained on the
      endocardial surface of bullfrog atrium in directions parallel and perpendicular
      to the cardiac fibers. In the longitudinal fiber direction, the membrane
      depolarized for cathodal pulses (and hyperpolarized for anodal pulses) but only
      in a region within 445 +/- 112 microns (and 616 +/- 78 microns for anodal pulses)
      from the center of the electrode (n = 9). Outside this region, vm reversed
      polarity and reached a local maximum at 922 +/- 136 microns (and 988 +/- 117
      microns for anodal pulses) (n = 9). Beyond this point vm decayed to zero over a
      distance of 1.5-2 mm. In the transverse fiber direction, the membrane depolarized
      for cathodal pulses (and hyperpolarized for anodal pulses) at all distances from
      the electrode. The amplitude of the response decreased with distance from the
      electrode with an exponential decay constant of 343 +/- 110 microns for cathodal
      pulses and 253 +/- 91 microns for anodal pulses (n = 7). The results were
      qualitatively similar in both fiber directions when the atrium was bathed in a
      solution containing ionic channel blockers. A two-dimensional computer model was
      formulated for the case of highly anisotropic cardiac tissue and qualitatively
      accounts for nearly all the observed spatial and temporal behavior of vm in the
      two fiber directions. The relationships between vm and both the "activating
      function" and extracellular potential gradient are discussed.

PMID- 7647236
TI  - A role for calcium release-activated current (CRAC) in cholinergic modulation of
      electrical activity in pancreatic beta-cells.
AB  - S. Bordin and colleagues have proposed that the depolarizing effects of
      acetylcholine and other muscarinic agonists on pancreatic beta-cells are mediated
      by a calcium release-activated current (CRAC). We support this hypothesis with
      additional data, and present a theoretical model which accounts for most known
      data on muscarinic effects. Additional phenomena, such as the biphasic responses
      of beta-cells to changes in glucose concentration and the depolarizing effects of
      the sarco-endoplasmic reticulum calcium ATPase pump poison thapsigargin, are also
      accounted for by our model. The ability of this single hypothesis, that CRAC is
      present in beta-cells, to explain so many phenomena motivates a more complete
      characterization of this current.

PMID- 7647237
TI  - Permeability of dimyristoyl phosphatidylcholine/dipalmitoyl phosphatidylcholine
      bilayer membranes with coexisting gel and liquid-crystalline phases.
AB  - The passive permeation of glucose and a small zwitterionic molecule, methyl
      phosphoethanolamine, across two-component phospholipid bilayers (dimyristoyl
      phosphatidylcholine (DMPC)/dipalmitoyl phosphatidylcholine (DPPC) mixtures)
      exhibit a maximum when gel domains and fluid domains coexist. The permeability
      data of the two-phase bilayers cannot be fitted to single-rate kinetics, but are
      consistent with a Gaussian distribution of rate constants. In pure DMPC and DPPC
      as well as in their mixtures, at the temperature of the maximum excess heat
      capacity, the logarithm of the average permeability rate constants are linearly
      correlated with the mole fraction of DPPC in the total system. In addition, in
      the 50:50 mixture, the excess heat capacity values as well as the apparent
      fractions of interfacial lipid correlate with the logarithm of the excess
      permeabilities in the two-phase region. These results suggest that small polar
      molecules can cross the membrane at the interface between gel and fluid domains
      at a much faster rate than through the homogeneous phases; the acyl chains
      located at the domain interface experience lateral density fluctuations that are
      inversely proportional to their average length, and large enough to allow rapid
      transmembrane diffusion of the solute molecules. The distribution of the
      permeability rate constants may reflect temporal and spatial fluctuations of the
      lipid composition at the phase boundaries.

PMID- 7647238
TI  - Behavior of cholesterol and spin-labeled cholestane in model bile systems studied
      by electron spin resonance and synchrotron x-ray.
AB  - The behavior of mixed bile salt micelles consisting of sodium taurocholate, egg
      phosphatidylcholine, and cholesterol has been studied by ESR spin labeling and
      synchrotron x-ray scattering. Consistent with published phase diagrams, pure and
      mixed bile salt micelles have a limited capacity to incorporate and, hence,
      solubilize cholesterol. Excess cholesterol crystallizes out, a process that is
      readily detected both by ESR spin labeling using 3-doxyl-5 alpha-cholestane as a
      probe for cholesterol and synchrotron x-ray scattering. Both methods yield
      entirely consistent results. The crystallization of cholesterol from mixed bile
      salt micelles is indicated by the appearance of a magnetically dilute powder
      spectrum that is readily detected by visual inspection of the ESR spectra. Both
      the absence of Heissenberg spin exchange and the observation of a magnetically
      dilute powder spectrum provide evidence for the spin label co-crystallizing with
      cholesterol. In mixed bile salt micelles containing egg phosphatidylcholine, the
      solubility of cholesterol is increased as detected by both methods. With
      increasing content of phosphatidylcholine and increasing mole ratio
      cholesterol/phosphatidylcholine, the anisotropy of motion of the spin probe
      increases. The spin label 3-doxyl-5 alpha-cholestane is a useful substitute for
      cholesterol provided that it is used in dilute mixtures with excess cholesterol:
      the cholesterol/spin label mole ratio in these mixtures should be greater than
      100. Despite the structural similarity between the two compounds, there are still
      significant differences in their physico-chemical properties. These differences
      come to the fore when cholesterol is totally replaced by the spin-label: 3-doxyl
      5a-cholestane is significantly less soluble in bile salt and mixed bile salt
      micelles than cholesterol and, in contrast with cholesterol, it interacts only
      very weakly, if at all,with phosphatidylcholine. The potential of the ESR method
      for detecting cholesterol crystal growth in human bile is discussed.

PMID- 7647239
TI  - Very high frequency electron paramagnetic resonance of 2,2,6,6-tetramethyl-1
      piperidinyloxy in 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine liposomes:
      partitioning and molecular dynamics.
AB  - Partitioning and molecular dynamics of 2,2,6,6,-tetramethylpiperedine-1-oxyl
      (TEMPO) nitroxide radicals in large unilamellar liposomes (LUV) composed from 1,2
      dipalmitoyl-sn-glycero-3-phosphatidylcholine were investigated by using very high
      frequency electron paramagnetic resonance (EPR) spectroscopy. Experiments carried
      out at a microwave frequency of 94.3 GHz completely resolved the TEMPO EPR
      spectrum in the aqueous and hydrocarbon phases. An accurate computer simulation
      method combined with Levenberg-Marquardt optimization was used to analyze the
      TEMPO EPR spectra in both phases. Spectral parameters extracted from the
      simulations gave the actual partitioning of the TEMPO probe between the LUV
      hydrocarbon and aqueous phases and allowed analysis of picosecond rotational
      dynamics of the probe in the LUV hydrocarbon phase. In very high frequency EPR
      experiments, phase transitions in the LUV-TEMPO system were observed as sharp
      changes in both partitioning and rotational correlation times of the TEMPO probe.
      The phase transition temperatures (40.5 +/- 0.2 and 32.7 +/- 0.5 degrees C) are
      in agreement with previously reported differential scanning microcalorimetry
      data. Spectral line widths were analyzed by using existing theoretical
      expressions for motionally narrowed nitroxide spectra. It was found that the
      motion of the small, nearly spherical, TEMPO probe can be well described by
      anisotropic Brownian diffusion in isotropic media and is not restricted by the
      much larger hydrocarbon chains existing in ripple structure (P beta') or fluid
      bilayer structure (L alpha) phases.

PMID- 7647241
TI  - Rapid reversible formation of a metastable subgel phase in saturated
      diacylphosphatidylcholines.
AB  - Formation of well ordered lamellar subgel (SGII) phase in aqueous dispersions of
      L-dipalmitoylphosphatidylcholine upon cooling from the lamellar gel phase,
      without low-temperature equilibration, is observed in real time using synchrotron
      x-ray diffraction. It has the same lamellar repeat period as the gel phase from
      which it was formed but differs in its wide-angle diffraction pattern. The SGII
      phase forms at about 7 degrees C upon cooling at 2 degrees C/min. In temperature
      jump experiments at 1 degree C/s from 50 to -5 degrees C, the relaxation time of
      the lamellar gel-SGII transition is found to be approximately 15 s. The
      conversion between the lamellar gel and SGII phase is cooperative and rapidly
      reversible. Upon heating, it coincides in temperature with an endothermic event
      with a calorimetric enthalpy of 0.35 kcal/mol, the so-called sub-subtransition.
      Similar sub-subtransitions are also observed calorimetrically at temperatures
      approximately 10 degrees C below the subtransition, without low-temperature
      storage, in aqueous dispersions of L-dimyristoylphosphatidylcholine and L
      distearoylphosphatidylcholine, but not in racemic DL
      dipalmitoylphosphatidylcholine. The formation of the equilibrium lamellar
      crystalline Lc phase appears to take place only from within the SGII phase.

PMID- 7647240
TI  - X-ray diffraction study of lipid bilayer membranes interacting with amphiphilic
      helical peptides: diphytanoyl phosphatidylcholine with alamethicin at low
      concentrations.
AB  - A variety of amphiphilic helical peptides have been shown to exhibit a transition
      from adsorbing parallel to a membrane surface at low concentrations to inserting
      perpendicularly into the membrane at high concentrations. Furthermore, this
      transition has been correlated to the peptides' cytolytic activities. X-ray
      lamellar diffraction of diphytanoyl phosphatidylcholine-alamethicin mixtures
      revealed the changes of the bilayer structure with alamethicin concentration. In
      particular, the bilayer thickness decreases with increasing peptide concentration
      in proportion to the peptide-lipid molar ratio from as low as 1:150 to 1:47; the
      latter is near the threshold of the critical concentration for insertion. From
      the decreases of the bilayer thickness, one can calculate the cross sectional
      expansions of the lipid chains. For all of the peptide concentrations studied,
      the area expansion of the chain region for each adsorbed peptide is a constant
      280 +/- 20 A2, which is approximately the cross sectional area of an adsorbed
      alamethicin. This implies that the peptide is adsorbed at the interface of the
      hydrocarbon region, separating the lipid headgroups laterally. Interestingly, the
      chain disorder caused by a peptide adsorption tends to spread over a large area,
      as much as 100 A in diameter. The theoretical basis of the long range nature of
      bilayer deformation is discussed.

PMID- 7647242
TI  - Phase behavior and crystalline structures of cholesteryl ester mixtures: a C-13
      MASNMR study.
AB  - Cholesteryl esters are a transport and storage form of cholesterol in normal
      physiology but also a significant lipid in atherosclerotic plaques. To understand
      better the molecular properties of cholesteryl esters in tissues and plaques, we
      have studied the polymorphic and mesomorphic features of pure and mixed
      cholesteryl esters by solid state C-13 NMR with magic angle sample spinning
      (MASNMR). The temperature-dependent properties of two single components
      (cholesteryl linoleate (CL, C18:2) and cholesteryl linolenate (CLL, C18:3)), four
      binary systems (cholesteryl palmitate (CP, C16:0) with CL, CLL or cholesteryl
      oleate (CO, C18:1), and CO/CL), one ternary system (CO/CP/CL), and one quaternary
      system (CO/CP/CL/CLL) were studied. The mixing ratios were based on the
      composition of an atherosclerosis plaque dissected from a cholesterol-fed New
      Zealand white rabbit. C-13 MASNMR determined the phase transition temperatures,
      identified the phases present in all systems, and provided novel information
      about molecular structures. For example, solid CL exhibited a disordered
      structure with multiple molecular conformations, whereas pure CLL had a
      crystalline structure different from the three most commonly characterized forms
      (MLII, MLI, BL). In binary mixtures, the crystalline structure of each
      cholesteryl ester species was identified by its own characteristic resonances. It
      was found that CP always existed in its native BL form, but CL and CO were
      influenced by the composition of the mixture. CL was induced to form MLII
      crystals by the coexisting CP (55 wt%). When CO was cooled from the isotropic
      phase, it existed as a mixture of MLII and an amorphous form. The presence of CP
      significantly accelerated the conversion of the amorphous form to the MLII form.
      For the ternary mixture co-dried from chloroform, CL cocrystallized with CO in
      the MLII form and CP existed in BL form. Addition of a small amount of CLL
      slightly increased the heterogeneity of the solid mixture, but had little effect
      on the crystal structures or the phase transitions. C-13 MASNMR represents a
      powerful method for physical characterization of cholesteryl ester mixtures
      reflecting the composition of biological samples.

PMID- 7647243
TI  - Membrane interaction of a beta-structure-forming synthetic peptide comprising the
      116-139th sequence region of the cytotoxic protein alpha-sarcin.
AB  - alpha-Sarcin is a cytotoxic protein that strongly interacts with acid
      phospholipid vesicles. This interaction exhibits a hydrophobic component although
      alpha-sarcin is a highly polar protein. A peptide comprising the amino acid
      sequence corresponding to the 116-139th segment of the alpha-sarcin cytotoxin has
      been synthesized by a standard fluoren-9-yl-methoxycarbonyl-based solid phase
      method. Its primary structure is: (116)-NPGPARVIYTYPNKVFCGIIAHTK-(139). Two beta
      strands have been predicted in this region of alpha-sarcin, where the less polar
      stretches of the protein are found. The synthetic peptide interacts with
      negatively charged large unilamellar vesicles of either natural or synthetic
      phospholipids. An apparent fragmentation of the vesicles is produced by the
      peptide based on electron microscopy studies. The peptide promotes leakage of the
      intravesicular aqueous contents and lipid mixing of bilayers. The packing of the
      phospholipid molecules is greatly perturbed by the peptide, as deduced from the
      drastic changes induced by the peptide in cooperative properties associated with
      the phase transition of the bilayers. At saturating peptide/phospholipid ratios,
      the phase transition of dimyristoylphosphatidylglycerol vesicles is abolished.
      All of these effects are saturated at about 0.3 peptide/lipid molar ratio. The
      peptide adopts a mostly random structure in aqueous solution. A conformation
      composed of a high proportion of antiparallel beta-sheet is induced as a
      consequence of the interaction with the phospholipid vesicles in opposition to
      trifluoroethanol that promotes alpha-helical peptide structures, as deduced from
      circular dichroism measurements. The obtained results are discussed in terms of
      the potential involvement of the region comprising residues 116-139 of alpha
      sarcin in the hydrophobic interactions of this cytotoxic protein with membranes.

PMID- 7647244
TI  - 2H nuclear magnetic resonance order parameter profiles suggest a change of
      molecular shape for phosphatidylcholines containing a polyunsaturated acyl chain.
AB  - Solid-state 2H nuclear magnetic resonance spectroscopy was used to determine the
      orientational order parameter profiles for a series of phosphatidylcholines with
      perdeuterated stearic acid, 18:0d35, in position sn-1 and 18:1 omega 9, 18:2
      omega 6, 18:3 omega 3, 20:4 omega 6, 20:5 omega 3, or 22:6 omega 3 in position sn
      2. The main phase transition temperatures were derived from a first moment
      analysis, and order parameter profiles of sn-1 chains were calculated from
      dePaked nuclear magnetic resonance powder patterns. Comparison of the profiles at
      37 degrees C showed that unsaturation causes an inhomogenous disordering along
      the sn-1 chain. Increasing sn-2 chain unsaturation from one to six double bonds
      resulted in a 1.6-kHz decrease in quadrupolar splittings of the sn-1 chain in the
      upper half of the chain (or plateau region) and maximum splitting difference of
      4.4 kHz at methylene carbon 14. The change in chain order corresponds to a
      decrease in the 18:0 chain length of 0.4 +/- 0.2 A with 18:2 omega 6 versus 18:1
      omega 9 in position sn-2. Fatty acids containing three or more double bonds in sn
      2 showed a decrease in sn-1 chain length of 0.7 +/- 0.2 A compared with 18:1
      omega 9. The chain length of all lipids decreased with increasing temperature.
      Highly unsaturated phosphatidylcholines (three or more double bonds in sn-2) had
      shorter sn-1 chains, but the chain length was somewhat less sensitive to
      temperature. The profiles reveal that the sn-1 chain exhibits a selective
      increase in motional freedom in a region located toward the bottom half of the
      chain as sn-2 unsaturation is increased. This corresponds to an area increase
      around carbon atom number 14 that is three to four times greater than the
      increase for the top part of the chain. A similar asymmetric decrease in order,
      largest toward the methyl end of the chain, was observed when 1 -palmitoyl-2
      oleoylphosphatidylethanolamine goes from a lamellar to an inverse hexagonal (H,,)
      phase. This is consistent with a change to a more wedge-shaped space available
      for the acyl chain.

PMID- 7647245
TI  - Parallel inhibition of active force and relaxed fiber stiffness by caldesmon
      fragments at physiological ionic strength and temperature conditions: additional
      evidence that weak cross-bridge binding to actin is an essential intermediate for
      force generation.
AB  - Previously we showed that stiffness of relaxed fibers and active force generated
      in single skinned fibers of rabbit psoas muscle are inhibited in parallel by
      actin-binding fragments of caldesmon, an actin-associated protein of smooth
      muscle, under conditions in which a large fraction of cross-bridges is weakly
      attached to actin (ionic strength of 50 mM and temperature of 5 degrees C). These
      results suggested that weak cross-bridge attachment to actin is essential for
      force generation. The present study provides evidence that this is also true for
      physiological ionic strength (170 mM) at temperatures up to 30 degrees C,
      suggesting that weak cross-bridge binding to actin is generally required for
      force generation. In addition, we show that the inhibition of active force is not
      a result of changes in cross-bridge cycling kinetics but apparently results from
      selective inhibition of weak cross-bridge binding to actin. Together with our
      previous biochemical, mechanical, and structural studies, these findings support
      the proposal that weak cross-bridge attachment to actin is an essential
      intermediate on the path to force generation and are consistent with the concept
      that isometric force mainly results from an increase in strain of the attached
      cross-bridge as a result of a structural change associated with the transition
      from a weakly bound to a strongly bound actomyosin complex. This mechanism is
      different from the processes responsible for quick tension recovery that were
      proposed by Huxley and Simmons (Proposed mechanism of force generation in
      striated muscle. Nature. 233:533-538.) to represent the elementary mechanism of
      force generation.

PMID- 7647246
TI  - Mode of caldesmon binding to smooth muscle thin filament: possible projection of
      the amino-terminal of caldesmon from native thin filament.
AB  - The structure of smooth muscle thin filament was examined by various electron
      microscopy techniques, with special attention to the mode of caldesmon binding.
      Chemical cross-linking was positively used to avoid the dissociation of accessory
      proteins upon dilution. Caldesmon in reconstituted thin filament was observed as
      fine filamentous projections from thin filament. Native thin filament isolated
      from smooth muscle showed similarly numerous fine whisker-like projections by all
      the techniques employed here. Antibody against the amino-terminus of caldesmon
      labeled the end of such projections indicating the possibility that the amino
      terminal myosin binding moiety might stick out from the shaft of the thin
      filament. Such whiskers are often projected out as a cluster to the same side of
      native thin filament. Further, we could visualize the assembly of
      dephosphorylated heavy meromyosin (HMM) with native or reconstituted thin
      filament forming "nonproductive" complex in the presence of ATP. The association
      of HMM to the shaft of thin filament was through subfragment-2 moiety, in
      accordance with biochemical studies. Some HMM particles bound closer to the thin
      filament shaft, possibly suggesting the presence of the second myosin-binding
      site on caldesmon. Occasionally two kinds of HMM association as such coexisted at
      a single site on this filament in tandem. Thus, we constructed a structural model
      of thin filament. The proposed molecular arrangement is not only compatible with
      all the biochemical results but also provides additional support for our recent
      findings (E. Katayoma, G. C. Scott-Woo, and M. Ikebe (1995) J. Biol. Chem. 270,
      3919-3925) regarding the capability of caldesmon to induce dephosphorylated
      myosin filament, which explains the existence of thick filaments in relaxed
      smooth muscle cells.

PMID- 7647247
TI  - Identification of source of oscillations in apparent sarcomere length measured by
      laser diffraction.
AB  - The most widely used technique for dynamic estimates of sarcomere length in
      muscle is laser light diffraction. We have identified conditions under which
      artifactual oscillations can arise in apparent sarcomere length measured by this
      technique and report methods to reduce the effect. Altringham et al. (1984) first
      reported that the diffraction angle can exhibit one cycle of oscillation for each
      sarcomere length displacement of the illuminated portion of the fiber. We find
      that the amplitude of similar oscillations is strongly dependent on the intensity
      of light scattered from objects near the fiber and on the spacing between fiber
      and scatterer. The oscillations can be eliminated by minimizing scattered light
      and positioning the fiber a few millimeters from sources of scattering. A
      theoretical description shows that oscillations of this kind are expected from
      interference of scattered and diffracted light. Interference fringes were
      observed along the meridian of the pattern, and these moved during translation of
      either a fiber or a grating. The movement of fringes across the diffraction order
      shifts the centroid back and forth and, when associated with steady shortening,
      can give rise to "steps" and "pauses" in apparent striation spacing.

PMID- 7647249
TI  - Photophysics of the fluorescent K+ indicator PBFI.
AB  - The fluorescent indicator PBFI is widely used for the determination of
      intracellular concentrations of K+. To investigate the binding reaction of K+ to
      PBFI in the ground and excited states, steady-state and time-resolved
      measurements were performed. The fluorescence decay surface was analyzed with
      global compartmental analysis yielding the following values for the rate
      constants at room temperature in aqueous solution at pH 7.2: k01 = 1.1 x 10(9) s
      1, k21 = 2.7 x 10(8) M-1s-1, k02 = 1.8 x 10(9) s-1, and k12 = 1.4 x 10(9) s-1.
      k01 and k02 denote the respective deactivation rate constants of the K+ free and
      bound forms of PBFI in the excited state. k21 represents the second-order rate
      constant of binding of K+ to the indicator in the excited state whereas k12 is
      the first-order rate constant of dissociation of the excited K(+)-PBFI complex.
      From the estimated values of k12 and k21, the dissociation constant Kd* in the
      excited state was calculated. It was found that pKd* (-0.7) is smaller than pKd
      (2.2). The effect of the excited-state reaction can be neglected in the
      determination of Kd and/or the K+ concentration. Therefore, intracellular K+
      concentrations can be accurately determined from fluorimetric measurements by
      using PBFI as K+ indicator.

PMID- 7647250
TI  - Theory of fluorescence induction in photosystem II: derivation of analytical
      expressions in a model including exciton-radical-pair equilibrium and restricted
      energy transfer between photosynthetic units.
AB  - The theoretical relationships between the fluorescence and photochemical yields
      of PS II and the fraction of open reaction centers are examined in a general
      model endowed with the following features: i) a homogeneous, infinite PS II
      domain; ii) exciton-radical-pair equilibrium; and iii) different rates of exciton
      transfer between core and peripheral antenna beds. Simple analytical relations
      are derived for the yields and their time courses in induction experiments. The
      introduction of the exciton-radical-pair equilibrium, for both the open and
      closed states of the trap, is shown to be equivalent to an irreversible trapping
      scheme with modified parameters. Variation of the interunit transfer rate allows
      continuous modulation from the case of separated units to the pure lake model.
      Broadly used relations for estimating the relative amount of reaction centers
      from the complementary area of the fluorescence kinetics or the photochemical
      yield from fluorescence levels are examined in this framework. Their dependence
      on parameters controlling exciton decay is discussed, allowing assessment of
      their range of applicability. An experimental induction curve is analyzed, with a
      discussion of its decomposition into alpha and beta contributions. The
      sigmoidicity of the induction kinetics is characterized by a single parameter J
      related to Joliot's p, which is shown to depend on both the connectivity of the
      photosynthetic units and reaction center parameters. On the other hand, the
      relation between J and the extreme fluorescence levels (or the deviation from the
      linear Stern-Volmer dependence of 1/phi f on the fraction of open traps) is
      controlled only by antenna connectivity. Experimental data are consistent with a
      model of connected units for PS II alpha, intermediate between the pure lake
      model of unrestricted exciton transfer and the isolated units model.

PMID- 7647248
TI  - Analysis of local helix bending in crystal structures of DNA oligonucleotides and
      DNA-protein complexes.
AB  - Sequence-dependent bending of the helical axes in 112 oligonucleotide duplex
      crystal structures resident in the Nucleic Acid Database have been analyzed and
      compared with the use of bending dials, a computer graphics tool. Our analysis
      includes structures of both A and B forms of DNA and considers both uncomplexed
      forms of the double helix as well as those bound to drugs and proteins. The
      patterns in bending preferences in the crystal structures are analyzed by base
      pair steps, and emerging trends are noted. Analysis of the 66 B-form structures
      in the Nucleic Acid Database indicates that uniform trends within all pyrimidine
      purine and purine-pyrimidine steps are not necessarily observed but are found
      particularly at CG and GC steps of dodecamers. The results support the idea that
      AA steps are relatively straight and that larger roll bends occur at or near the
      junctions of these A-tracts with their flanking sequences. The data on 16
      available crystal structures of protein-DNA complexes indicate that the majority
      of the DNA bends induced via protein binding are sharp localized kinks. The
      analysis of the 30 available A-form DNA structures indicates that these
      structures are also bent and show a definitive preference for bending into the
      deep major groove over the shallow minor groove.

PMID- 7647251
TI  - Two-dimensional crystallization of avidin on biotinylated lipid monolayers.
AB  - Two-dimensional crystals of avidin were obtained on mixed lipid monolayers
      containing biotinylated lipids (N-biotinyl-dipalmitoyl-L-alpha-phosphatidyl
      ethanolamine and dioleoyl phosphatidyl choline) by specific interaction. Image
      analysis of electron micrographs of these crystals revealed p2 symmetry with the
      unit cell parameters a = 66 +/- 2 A, b = 68 +/- 1 A, and gamma = 121 +/- 4
      degrees. The projection map showed, at a resolution of about 27 A, that the four
      subunits within one avidin molecule are separated into two parts. Comparison
      between avidin and streptavidin reveals that avidin molecule binds to the lipid
      monolayer in an orientation similar to that of streptavidin.

PMID- 7647253
TI  - Electron paramagnetic resonance of the excited triplet state of metal-free and
      metal-substituted cytochrome c.
AB  - The photoactivated metastable triplate states of the porphyrin (free-base, i.e.,
      metal-free) zinc and tin derivatives of horse cytochrome c were investigated
      using electron paramagnetic resonance. Zero-field splitting parameters, line
      shape, and Jahn-Teller distortion in the temperature range 3.8-150 K are
      discussed in terms of porphyrin-protein interactions. The zero-field splitting
      parameters D for the free-base, Zn and Sn derivatives are 465 x 10(-4), 342 x 10(
      4) and 353 x 10(-4) cm-1, respectively, and are temperature invariant over the
      temperature ranges studied. AN E value at 4 K of 73 x 10(-4) cm-1 was obtained
      for Zn cytochrome c, larger than any previously found for Zn porphyrins
      derivatives of hemeproteins, showing that the heme site of cytochrome c imposes
      an asymmetric field. Though the E value for Zn cytochrome c is large, the
      geometry of the site appears quite constrained, as indicated by a spectral line
      shape showing a single species. Intersystem crossing occurred predominantly to
      the T2 > zero-field spin sublevel. EPR line shape changes with respect to
      temperature of Zn cyt c are interpreted in terms of vibronic coupling, and a
      maximum Jahn-Teller crystal-field splitting of approximately 180 cm-1 is
      obtained. Sn cytochrome c in comparison with the Zn protein exhibits a
      photoactivated triplet line shape that is less well resolved in the X-Y region.
      The magnitude of E value is approximately 60 x 10(-4) cm-1 at 4 K; its value
      rapidly tends toward zero with increasing temperature, from which a value for the
      Jahn-Teller crystal-field splitting of > or = 40 cm-1 is estimated. In contrast
      to those for the metal cytochromes, the magnitude of E value for the free-base
      derivative was essentially zero at all temperatures studied. This finding is
      discussed as a consequence of an excited-state tautomerization process that
      occurs even at 4 K.

PMID- 7647254
TI  - Dynamics of hydrogen atoms in superoxide dismutase by quasielastic neutron
      scattering.
AB  - The low energy dynamic of the enzyme Cu,Zn superoxide dismutase have been
      investigated by means of quasielastic neutron scattering in the temperature range
      4-320 K. Below 200 K the scattering is purely elastic, while above this
      temperature a pronounced decrease in the elastic intensity is observed, together
      with the onset of a small quasielastic component. This behavior is similar to
      that previously observed in other more flexible globular proteins, and can be
      attributed to transitions between slightly different conformational substates of
      the protein tertiary structure. The presence of only a small quasielastic
      component, whose intensity is < or = 25% of the total spectrum, is related to the
      high structural rigidity of this protein.

PMID- 7647252
TI  - Ligand binding to heme proteins. V. Light-induced relaxation in proximal mutants
      L89I and H97F of carbonmonoxymyoglobin.
AB  - We have studied the proximal mutants L89I and H97F of MbCO with FTIR and
      temperature-derivative spectroscopy at temperatures between 10 and 160 K. The
      mutations give rise only to minor alterations of the stretch spectra of the bound
      and photodissociated CO ligand. The most pronounced difference is a larger
      population in the A3 substate at approximately 1930 cm-1 in the mutants. The
      barrier distributions, as determined by temperature-derivative spectroscopy, are
      very similar to native MbCO after short illumination. Extended illumination leads
      to substantial increases of the rebinding barriers in native MbCO and the
      proximal mutants. A larger fraction of light-relaxed states is found in the
      proximal mutants, implying that the conformational energy landscape has been
      modified to more easily allow light-induced transitions. These and other
      spectroscopic data imply that the large changes in the binding properties are
      brought about by a light-induced conformational relaxation involving the
      structure at the heme iron. Similarities with spectral hole-burning studies and
      physical models are discussed.

PMID- 7647255
TI  - Mossbauer spectroscopy on nonequilibrium states of myoglobin: a study of r-t
      relaxation.
AB  - A frozen solution of 57Fe-enriched metmyoglobin was irradiated by x rays at 77 K.
      Mossbauer spectra showed a reduction of Fe(III) high spin by thermalized
      electrons and a production of a metastable Fe(II) low spin myoglobin complex with
      H2O at its sixth coordination site. The relaxation of the intermediate was
      investigated by Mossbauer spectroscopy as a function of temperature and time. The
      relaxation process starts above 140 K and is fully completed at approximately 200
      K. At temperatures between 140 and 200 K, the relaxation lasts for hours and is
      nonexponential in time. Up to 180 K, the process can be described satisfactorily
      by a gamma distribution of activation enthalpies with an Arrhenius relation for
      the rate coefficient. The temperature and time dependence of the Mossbauer
      parameters indicates structural changes in the active center of the protein as
      early as 109 K that continue for several hours at higher temperatures. Above 180
      K, structural rearrangements involving the whole protein molecule lead to a shift
      and narrowing of the barrier height distribution.

PMID- 7647256
TI  - Electron-electron spin-spin interaction in spin-labeled low-spin methemoglobin.
AB  - Nitroxyl free radical electron spin relaxation times for spin-labeled low-spin
      methemoglobins were measured between 6 and 120 K by two-pulse electron spin echo
      spectroscopy and by saturation recovery electron paramagnetic resonance (EPR).
      Spin-lattice relaxation times for cyano-methemoglobin and imidazole-methemoglobin
      were measured between 8 and 25 K by saturation recovery and between 4.2 and 20 K
      by electron spin echo. At low temperature the iron electron spin relaxation rates
      are slow relative to the iron-nitroxyl electron-electron spin-spin splitting. As
      temperature is increased, the relaxation rates for the Fe(III) become comparable
      to and then greater than the spin-spin splitting, which collapses the splitting
      in the continuous wave EPR spectra and causes an increase and then a decrease in
      the nitroxyl electron spin echo decay rate. Throughout the temperature range
      examined, interaction with the Fe(III) increases the spin lattice relaxation rate
      (1/T1) for the nitroxyl. The measured relaxation times for the Fe(III) were used
      to analyze the temperature-dependent changes in the spin echo decays and in the
      saturation recovery (T1) data for the interacting nitroxyl and to determine the
      interspin distance, r. The values of r for three spin-labeled methemoglobins were
      between 15 and 15.5 A, with good agreement between values obtained by electron
      spin echo and saturation recovery. Analysis of the nitroxyl spin echo and
      saturation recovery data also provides values of the iron relaxation rates at
      temperatures where the iron relaxation rates are too fast to measure directly by
      saturation recovery or electron spin echo spectroscopy. These results demonstrate
      the power of using time-domain EPR measurements to probe the distance between a
      slowly relaxing spin and a relatively rapidly relaxing metal in a protein.

PMID- 7647258
TI  - Nuclear magnetic resonance spectra for l > 1 spins in dynamically heterogeneous
      systems with chemical exchange among environments.
AB  - Nuclear magnetic resonance spectra for nuclei with spin l > 1 are considered in
      cases in which the observed nucleus may sample a rotationally immobilized and an
      isotropic environment that are coupled by a chemical exchange process. Spectra
      are simulated for the central (1/2, -1/2) transition for a 3/2 nucleus as a
      function of the concentrations of the two environments and as a function of the
      exchange rate between them. It is shown that a crucial feature determining the
      shape of the observable spectra is the spatial extent or the local order in the
      immobilized phase. In the case for which all rotationally immobilized sites
      sampled by the exchanging nucleus are identically oriented but where there is a
      distribution of these microdomain orientations with respect to the magnetic field
      direction, a powder pattern for the central transition is observed that carries
      whatever dynamic information may be derived from it. In the fast exchange limit,
      the width of the powder pattern scales inversely with the concentration of the
      isotropic environment as usual. In the intermediate exchange regimes, a complex
      line shape results that may mask the anisotropic character of the spectrum. In
      the slow exchange limit, superposition of the spectral contributions results;
      however, if the isotropic environment concentration is significantly larger than
      the anisotropic environment concentration, the anisotropic contribution is very
      difficult to detect because of the dynamic range problem and the possibly large
      difference in the effective line widths. In the case for which the exchanging
      nucleus samples a considerable distribution of rotationally immobilized site
      orientations, the anisotropic character of the spectrum is lost and a super
      Lorentzian line shape results. These effects are demonstrated experimentally by
      35Cl nuclear magnetic resonance spectra obtained on a lamellar liquid crystal
      that is modified with the addition of a thiolmercurate to provide a site of large
      quadrupole coupling constant and with cross-linked bovine serum albumin gels.

PMID- 7647257
TI  - Understanding the cytochrome c oxidase proton pump: thermodynamics of redox
      linkage.
AB  - The cytochrome c oxidase complex (CcO) catalyzes the four-electron reduction of
      dioxygen to water by using electrons from ferrocytochrome c. Redox free energy
      released in this highly exergonic process is utilized to drive the translocation
      of protons across a transmembrane electrochemical gradient. Although numerous
      chemical models of proton pumping have been developed, few attempts have been
      made to explain the stepwise transfer of energy in the context of proposed
      protein conformational changes. A model is described that seeks to clarify the
      thermodynamics of the proton pumping function of CcO and that illustrates the
      importance of electron and proton gating to prevent the occurrence of the more
      exergonic electron leak and proton slip reactions. The redox energy of the CcO
      membrane system is formulated in terms of a multidimensional energy surface
      projected into two dimensions, a nuclear coordinate associated with electron
      transfer and a nuclear coordinate associated with elements of the proton pump.
      This model provides an understanding of how a transmembrane electrochemical
      gradient affects the efficiency of the proton pumping process. Specifically,
      electron leak and proton slip reactions become kinetically viable as a result of
      the greater energy barriers that develop for the desired reactions in the
      presence of a transmembrane potential.

PMID- 7647259
TI  - Determination of the orientation distribution of adsorbed fluorophores using
      TIRF. I. Theory.
AB  - The spectroscopic technique total internal reflection fluorescence can be used
      for determination of the orientation of adsorbed fluorescent molecules. The
      underlying theory is presented in general terms and elaborated in detail for the
      case that the fluorescent group is a porphyrin ring. It is shown that order
      parameters of the orientation distribution can be obtained if both the
      fluorescence intensity and its polarization are measured as functions of the
      polarization of the incident laser beam. From these order parameters an
      approximation of the orientation distribution can be derived by the maximum
      entropy method.

PMID- 7647260
TI  - Determination of the orientation distribution of adsorbed fluorophores using
      TIRF. II. Measurements on porphyrin and cytochrome c.
AB  - The theory for determination of the orientation of adsorbed fluorescent molecules
      using total internal reflection fluorescence, as explained in part I of this
      series, is illustrated by measurements on adsorbed tetramethylpyridinium
      porphyrin (H2TMPyP) and porphyrin cytochrome c molecules. The results are
      encouraging, although for porphyrin cytochrome c the scatter in the obtained
      order parameters is substantial. For H2TMPyP molecules adsorbed on glass the
      orientation distribution depends on the solution concentration. At low
      concentration, the H2TMPyP molecules are more or less randomly oriented, whereas
      at high concentrations a broad distribution around an angle of 46 degrees between
      the porphyrin plane and surface was found. For cytochrome c adsorbed on glass and
      indium tin oxide it was impossible to interpret the data in terms of orientation
      distributions because of the scatter in the results. The total fluorescence as a
      function of the polarization angle psi of the incident light beam corresponds to
      an average angle between the porphyrin group and the surface of 30 degrees-40
      degrees. Despite the strong electric dipole moment of the protein, the
      orientation distribution seems to be independent on the (imposed) electrical
      potential of the interface.

PMID- 7647261
TI  - Sensitive force technique to probe molecular adhesion and structural linkages at
      biological interfaces.
AB  - Adhesion and cytoskeletal structure are intimately related in biological cell
      function. Even with the vast amount of biological and biochemical data that
      exist, little is known at the molecular level about physical mechanisms involved
      in attachments between cells or about consequences of adhesion on the material
      structure. To expose physical actions at soft biological interfaces, we have
      combined an ultrasensitive transducer and reflection interference microscopy to
      image submicroscopic displacements of probe contact with a test surface under
      minuscule forces. The transducer is a cell-size membrane capsule pressurized by
      micropipette suction where displacement normal to the membrane under tension is
      proportional to the applied force. Pressure control of the tension tunes the
      sensitivity in operation over four orders of magnitude through a range of force
      from 0.01 pN up to the strength of covalent bonds (approximately 1000 pN)! As the
      surface probe, a microscopic bead is biochemically glued to the transducer with a
      densely-bound ligand that is indifferent to the test surface. Movements of the
      probe under applied force are resolved down to an accuracy of approximately 5 nm
      from the interference fringe pattern created by light reflected from the bead.
      With this arrangement, we show that local mechanical compliance of a cell surface
      can be measured at a displacement resolution set by structural fluctuations. When
      desired, a second ligand is bound sparsely to the probe for focal adhesion to
      specific receptors in the test surface. We demonstrate that monitoring
      fluctuations in probe position at low transducer stiffness enhances detection of
      molecular adhesion and activation of cytoskeletal structure. Subsequent loading
      of an attachment tests mechanical response of the receptor-substrate linkage
      throughout the force-driven process of detachment.

PMID- 7647262
TI  - Photobleaching kinetics of fluorescein in quantitative fluorescence microscopy.
AB  - An investigation on the photobleaching behavior of fluorescein in microscopy was
      carried out through a systematic analysis of photobleaching mechanisms. The
      individual photochemical reactions of fluorescein were incorporated into a
      theoretical analysis and mathematical simulation to study the photochemical
      processes leading to photobleaching of fluorescein in microscopy. The
      photobleaching behavior of free and bound fluorescein has also been investigated
      by experimental means. Both the theoretical simulation and experimental data show
      that photobleaching of fluorescein in microscopy is, in general, not a single
      exponential process. The simulation suggests that the non-single-exponential
      behavior is caused by the oxygen-independent, proximity-induced triplet-triplet
      or triplet-ground state dye reactions of bound fluorescein in microscopy. The
      single-exponential process is a special case of photobleaching behavior when the
      reactions between the triplet dye and molecular oxygen are dominant.

PMID- 7647263
TI  - Kinetics of cytosolic Ca2+ concentration after photolytic release of 1-D-myo
      inositol 1,4-bisphosphate 5-phosphorothioate from a caged derivative in guinea
      pig hepatocytes.
AB  - The influence of 1-D-myo-inositol 1,4,5-trisphosphate (InsP3) breakdown by InsP3
      5-phosphatase in determining the time course of Ca2+ release from intracellular
      stores was investigated with flash photolytic release of a stable InsP3
      derivative, 5-thio-InsP3, from a photolabile caged precursor. The potency and
      Ca(2+)-releasing properties of the biologically active D isomers of 5-thio-InsP3
      and InsP3 itself were compared by photolytic release in guinea pig hepatocytes.
      After a light flash, cytosolic free calcium concentration ([Ca2+]i) showed an
      initial delay before rising quickly to a peak and declining more slowly to
      resting levels, with time course and amplitude generally similar to those seen
      with photolytic release of InsP3. Differences were a three- to eightfold lower
      potency of 5-thio-InsP3 in producing Ca2+ release, much longer delays between
      photolytic release and Ca2+ efflux with low concentrations of 5-thio-InsP3 than
      with InsP3, and persistent reactivation of Ca2+ release, producing periodic
      fluctuations of cytosolic [Ca2+]i with high concentrations of 5-thio-InsP3 but
      not InsP3 itself. The lower potency of 5-thio-InsP3 may be a result of a lower
      affinity for closed receptor/channels or a lower open probability of liganded
      receptor/channels. The longer delays with 5-thio-InsP3 at low concentration
      suggest that metabolism of InsP3 by 5-phosphatase may reduce the concentration
      sufficiently to prevent receptor activation and may have a similar effect on
      InsP3 concentration during hormonal activation. The maximal rate of rise of
      [Ca2+]i, the duration of the period of high Ca2+ efflux, and the initial decline
      of [Ca2+]i are similar with5-thio-lnsP3 and lnsP3, indicating that lnsP3
      breakdown is not important in terminating Ca2+ release. The second activation
      ofInsP3 receptors with 5-thio-lnsP3 and particularly the sustained periodic
      fluctuations of [Ca2+]i indicate persistence of 5-thio-lnsP3,suggesting that
      InsP3 breakdown prevents reactivation of InsP3 receptors. The photochemical
      properties of 1-(2-nitrophenyl)-ethyl caged 5-thio-lnsP3 are photolytic quantum
      yield = 0.57 (cf. 0.65 for caged InsP3) and rate of photolysis = 87 s-I (half
      life approximately 8 ms; cf. 3 ms for caged lnsP3; pH7.1; ionic strength, 0.2 M;
      21 OC). Caged 5-thio-lnsP3 at concentrations up to 360 pM did not activate lnsP3
      receptors to produce Ca2+ release or block Ca2+ release by free 5-thio-lnsP3.

PMID- 7647264
TI  - Dynamics of cell membrane permeability changes at supraphysiological
      temperatures.
AB  - A quantitative fluorescent microscopy system was developed to characterize, in
      real time, the effects of supraphysiological temperatures between 37 degrees and
      70 degrees C on the plasma membrane of mouse 3T3 fibroblasts and isolated rat
      skeletal muscle cells. Membrane permeability was assessed by monitoring the
      leakage as a function of time of the fluorescent membrane integrity probe
      calcein. The kinetics of dye leakage increased with increasing temperature in
      both the 3T3 fibroblasts and the skeletal muscle cells. Analytical solutions
      derived from a two-compartment transport model showed that, for both cell types,
      a time-dependent permeability assumption provided a statistically better fit of
      the model predictions to the data than a constant permeability assumption. This
      finding suggests that the plasma membrane integrity is continuously being
      compromised while cells are subjected to supraphysiological temperatures.

PMID- 7647265
TI  - Adsorption properties of polar/apolar inducers at a charged interface and their
      relevance to leukemia cell differentiation.
AB  - The interfacial adsorption properties of polar/apolar inducers of cell
      differentiation (PAIs) were studied on a mercury electrode. This study, on a
      clean and reproducible charged surface, unraveled the purely physical
      interactions among these compounds and the surface, apart from the complexity of
      the biological membrane. The interfacial behavior of two classical inducers,
      hexamethylenebisacetamide (HMBA) and dimethylsulfoxide, was compared with that of
      a typical apolar aliphatic compound, 1-octanol, that has a similar hydrophobic
      moiety as HMBA but a much smaller dipolar moment. Both HMBA and Octanol adsorb
      flat in contact with the surface because of hydrophobic forces, with a very
      similar free energy of adsorption. However, the ratio of polar to apolar moieties
      in PAIs turned out to be crucial to drive the adsorption maximum toward
      physiological values of surface charge density, where octanol is desorbed. The
      electrostatic effects in the interfacial region reflected the adsorption
      properties: the changes in the potential drop across the interfacial region as a
      function of the surface charge density, in the physiological range, were opposite
      in PAIs as compared with apolar aliphatic compounds, as exemplified by octanol.
      This peculiar electrostatic effect of PAIs has far-reaching relevance for the
      design of inducers with an adequate therapeutic index to be used in clinical
      trials.

PMID- 7647266
TI  - Tubal surgery versus assisted reproduction: assessing their role in infertility
      therapy.
AB  - The majority of women with tubal/pelvic infective damage have a poor prognosis
      for natural conception, and in-vitro fertilization and embryo transfer would be a
      better primary choice. Other determining factors are sperm disorder or the
      woman's age, and personal issues may be of overriding importance. The most
      important requirement in the first place, however, is well defined, comparable
      statistical information on time-specific cumulative pregnancy rates related to
      specific diagnostic features. The main aims of this review are to analyze the
      most useful comparable data available and present them in graphical form for easy
      reference and clear understanding (by the patients too), and to try to derive a
      practically simple and prognostically valuable diagnostic classification.

PMID- 7647267
TI  - Ectopic pregnancy: new advances in diagnosis and treatment.
AB  - Recent reports affirm that ectopic pregnancy has become a medical rather than a
      surgical disease. Early diagnosis is the key to effective nonsurgical treatment.
      Diagnostic algorithms using serum progesterone, serial beta-human chorionic
      gonadotropin measurements, ultrasound, and office curettage now make definitive
      diagnosis possible without laparoscopy. Laparoscopic salpingostomy, the surgical
      gold standard, is an effective therapy but carries surgical complications and is
      expensive. Systemic variable dose methotrexate produces outcomes close to
      laparoscopic salpingostomy in similar patients. Single dose systemic methotrexate
      and intratubal methotrexate appear to be less effective. In many cases, ectopic
      pregnancies do not meet suitable medical criteria and still require surgery. The
      challenge today is identifying patients at risk and bringing them into the system
      during the early first trimester when treatment is simple.

PMID- 7647268
TI  - The diagnosis and treatment of male infertility.
AB  - Male factor infertility is a heterogeneous disorder, a factor that precludes the
      development of either a single laboratory test to predict sperm fertility
      potential or a single therapy to improve fertility. A better understanding of the
      pathophysiology of the disorder will ultimately lead to more clearly defined
      diagnostic categories and specific treatment regimens.

PMID- 7647269
TI  - Enhancement of fertilization by micromanipulation.
AB  - Micromanipulation techniques have been successfully applied to human gametes to
      assist fertilization when normal function is impaired. The past few years have
      witnessed the rapid evolution and clinical incorporation of this technology. The
      unprecedented efficiency of intracytoplasmic sperm injection far surpasses all
      previous methods. This method has thus become the best treatment option for many
      forms of male infertility.

PMID- 7647270
TI  - Cryopreservation of human embryos and oocytes.
AB  - Human embryo cryopreservation is now a fully established adjunct to assisted
      reproduction, with thawed embryos implanting at a rate approaching that of fresh
      embryos. As with fresh embryos, the quality of frozen-thawed embryos is affected
      by patient age at the time of oocyte retrieval, and by culture conditions.
      Ovarian stimulation incorporating gonadotropin-releasing hormone analogs does not
      appear to be detrimental to cryopreservation success, and natural or artificial
      thaw cycles seem equally effective. Successful cryopreservation seems feasible
      for one- to eight-cell embryos and blastocysts using a variety of protocols.
      Selection criteria for embryos to be frozen can vary, and embryo quality has the
      most significant impact on post-cryopreservation viability. Unfertilized oocyte
      cryopreservation is coming closer to routine clinical application.

PMID- 7647271
TI  - Oocyte and embryo donation.
AB  - Oocyte and embryo donation has become increasingly common over the past 10 years.
      Today, it is successfully used to treat women with a variety of disorders,
      including ovarian failure, avoidance of genetic disease transmission, declining
      ovarian function, poor oocyte quality following conventional assisted
      reproduction, and age-related infertility. Success rates do not appear to vary
      with the recipient's age or diagnosis, with live birth rates in the 25-35% range.
      Oocyte and embryo donation represent the most efficacious method of assisted
      reproduction.

PMID- 7647272
TI  - Ethical issues related to the new reproductive technologies.
AB  - Society's attitudes about the importance of genetic affiliations, both within and
      outside the family structure, as well as its attitudes about the appropriate
      limits on eugenic practices, strongly influence how physicians and researchers
      approach ethical problems related to reproduction technology. Scientific advances
      require us constantly to reassess ethical values, as well as the effect of
      technology on ethical values, and vice versa. Physicians' personal ethics, as
      well as those of their colleagues, are an integral and important part of the
      physician-patient relationship, which is the foundation of sound clinical ethics.

PMID- 7647273
TI  - Polycystic ovary syndrome: aetiology and management.
AB  - Although much clearer ideas concerning therapeutic approaches to patients with
      polycystic ovary syndrome are developing, the etiology of this enigmatic but
      common syndrome continues to be a fruitful source of discussion and debate. There
      is renewed interest in laparoscopic surgical methods of treatment.

PMID- 7647274
TI  - Intraovarian factors regulating ovarian function.
AB  - Ovarian folliculogenesis is a dynamic process marked by exponential expansion and
      differentiation of the granulosa cells, oocyte maturation, ovulation and corpus
      luteum formation. Although the central roles of gonadotropins and gonadal
      steroids in this explosive agenda are well accepted, the variable fate of
      follicles afforded comparable stimulation within the same ovary suggests the
      existence of an additional intraovarian system comprised of regulating species
      that 'fine-tune' the blood-borne hormones.

PMID- 7647275
TI  - Menopause: refining benefits and risks of hormone replacement therapy.
AB  - In terms of our understanding of menopause and hormone replacement therapy, 1993
      1994 did not see any seminal or definitive publications. However, the data that
      were published have helped refine our understanding of the benefits and risks of
      hormone replacement therapy. This article presents further evidence for the
      protective effects of hormone replacement therapy in preventing osteoporosis and
      arterial disease, including direct gonadal hormone effects upon the vessel wall;
      discusses changes in attitudes to progestogen additions, withdrawal bleeding and
      endometrial status; reviews controversies over the relationship between hormone
      replacement therapy and breast cancer risk, and briefly mentions a new device for
      delivery of non-oral oestradiol.

PMID- 7647276
TI  - Growth hormone and reproduction.
AB  - It has become apparent that the reproductive and somatotrophic axes may often be
      interlinked, and that the ovary may be a target for growth hormone action. Within
      the ovary, there exists a complex regulating system involving growth factors,
      which promote gonadotrophin action, and their binding proteins, which modulate
      these actions. The realization of the existence of this fine-tuning system has
      prompted clinical trials of cotreatment with growth hormone and gonadotrophins,
      mainly directed at the poor responder to gonadotrophin stimulation. The effect of
      this treatment is dependent on the hormonal status and 'ovarian age' of the
      patient. Studies have delineated a possible role for additional growth hormone in
      those with a lack of growth hormone but it has little place in a normal system.
      Although an improvement in pregnancy rate has not yet emerged, more research
      should be forthcoming on the effect of growth hormone and growth factors on the
      follicle, oocyte and endometrium and their possible role in polycystic ovary
      syndrome.

PMID- 7647277
TI  - The etiology of hyperandrogenism in women.
AB  - This review considers recent evidence which has implicated steroidogenic
      alterations as elements on the etiology of the androgen excess associated with
      polycystic ovary syndrome. The importance of circulating dehydroepiandrosterone
      sulphate as a precursor for ovarian follicular testosterone is discussed and
      evaluated in the face of indications that the activity of P450-c17-alpha
      hydroxylase is altered at both adrenal and ovarian level in polycystic ovary
      syndrome. The impact of weight and insulin resistance on circulating
      dehydroepiandrosterone concentrations is discussed, and related to the endocrine
      changes in polycystic ovary syndrome. Androgen excess in women arises from
      multiple endocrine disturbances, which evidently commonly include the
      steroidogenic pathways.

PMID- 7647279
TI  - Why does a viral hepatitis become chronic? (the HBV model)

PMID- 7647278
TI  - The management of immune thrombocytopenic purpura in pregnancy.

PMID- 7647280
TI  - Immunotherapy of chronic hepatitis B by anti HBV vaccine.
AB  - Vaccine therapy is now used in various infectious diseases. The hepatitis B virus
      (HBV) leads to chronic infection in around 5% of patients with a high risk of
      chronic active hepatitis which may result in cirrhosis and hepatocellular
      carcinoma. The partial efficacy of antiviral therapies (40% of sustained
      inhibition of HBV replication), their cost, the numerous side effects and the
      immune-mediated pathology of HBV infection explain the emergence of new immune
      therapies in treating HBV infection. Experimental and clinical arguments are in
      favor of vaccine therapy in HBV chronic infection. Thirty-two consecutive chronic
      HBsAg carriers with chronic hepatitis and detectable serum HBV DNA were given 3
      standard injections of the GenHevac B vaccine at one month intervals. Six months
      after the first injection, 12 patients (37.5%) had undetectable HBV DNA while 3
      others showed significant decrease in HBV DNA titers. Eight of these 15
      responders received a standard course of alpha-interferon (5 MU thrice weekly
      subcutaneously for 4 months) and all still had undetectable HBV replication. By
      contrast, among 13 (of the 17) non responders to vaccine who were given alpha
      interferon, only 3 stopped HBV replication. In summary, serum HBV DNA disappeared
      in 18 of the 32 patients (53.1%) who were given vaccine therapy, with or without
      interferon. Vaccination was uneventful. Active immune therapy against HBV appears
      as efficient and less expensive than antiviral therapies in stopping HBV
      replication. Such a result should be confirmed by controlled randomized trials.

PMID- 7647281
TI  - Alpha interferon treatment of chronic hepatitis C.
AB  - Hepatitis C virus infection is a common disease with a high propensity to
      progress towards chronicity. Alpha interferon has been proposed to halt
      progression of the disease and prevent the development of more severe liver
      diseases such as cirrhosis and hepatocellular carcinoma. Unfortunately, less than
      20% of treated patients show a long-lasting ALT normalization and HCV-RNA
      negativity. Factors which might be predictive of a long term response to
      interferon are debated. Univariate analysis of data collected in randomized
      clinical studies, has shown that IFN dose, age, duration of disease, cirrhosis
      and early response (primary) to IFN were all predictors of a sustained response
      to IFN, but with differences in different studies. When data were analyzed by a
      multivariate analysis, short duration of the disease and absence of cirrhosis
      were found to predict long-term response to interferon. Finally, many evidences
      indicate that response rates to therapy may be better in patients with low
      pretreatment levels of HCV-RNA measured either by polymerase chain reaction (PCR)
      or the branched-DNA assay (b-DNA).

PMID- 7647282
TI  - Fibrosing cholestatic hepatitis and HBV after bone marrow transplantation.
AB  - Liver failure caused by reactivation of hepatitis B virus (HBV) is an uncommon
      complication of bone marrow transplantation. Fibrosing cholestatic hepatitis is a
      recently described liver lesion that develops in some patients undergoing liver
      transplantation for chronic HBV infection. The lesion is characterised by peri
      portal fibrosis, ballooning degeneration of hepatocytes, prominent cholestasis
      and paucity of inflammation. Recent data suggests it is a cytopathic effect of
      the pre-core mutant form of HBV with over-expression of viral antigens. Although
      only one case has so far been described associated with bone marrow
      transplantation (BMT) it is likely that increasing use of BMT in people with
      chronic HBV infection will lead to further patients being recognised.

PMID- 7647283
TI  - Hepatitis virus infections in heart transplant recipients.

PMID- 7647284
TI  - The anti-osteoporotic activity of amine-carboxyboranes in rodents.
AB  - Amine-carboxyboranes have been shown to prevent osteoporosis and loss of bone
      mass in rodents. In vitro studies using CF1 mouse pup calvaria and rat UMR-106
      osteosarcoma cells showed that amine-carboxyborane derivatives reduced
      significantly the loss of intracellular calcium into the growth medium from 10(
      4) to 10(-8) M over 48 hours. Amine-carboxyborane derivatives were more effective
      than calcitonin or simple boron salts. Calcium incorporation into these cells and
      proline incorporation into collagen was accelerated in the presence of amine
      carboxyboranes. The amine-carboxyborane derivatives effectively inhibited
      lysosomal and proteolytic enzymes as well as activities of serine elastase,
      prostaglandin cyclooxygenase, and 5'-lipoxygenase in mouse macrophages, human
      PMNs, leukocytes and Be Sal cells. IC50 values were in the range of 10(-6) M. In
      lactating ovariectomized female rats after administered amine-carboxyboranes for
      14 days at 8 mg/kg/day orally, the femur and humerus showed increased volume,
      weight, density and ash weight. Serum calcium levels were elevated significantly
      with minimum reductions on serum inorganic phosphate levels. Femur calcium levels
      were elevated after treatment with amine-carboxyborane derivatives, but not with
      etidronate. Humerus total lipids after 14 days were slightly elevated probably
      due to increased levels of triglycerides and phospholipids.

PMID- 7647285
TI  - Purine nucleotide metabolism in lymphocytes of B-cell chronic lymphocytic
      leukemia patients.
AB  - Purine nucleotides were studied in human peripheral blood lymphocytes from normal
      subjects and patients with chronic B-cell lymphocytic leukemia (B-CLL).
      Nucleotide content was determined by high performance liquid chromatography
      (HPLC). The overall rate of purine nucleotide synthesis was measured following
      the incorporation of 14C-formate into the nucleotides of a lymphocytic
      suspension. Results indicate a substantially reduced rate of purine nucleotide
      metabolism.

PMID- 7647286
TI  - Endogenous retroviral envelope peptide expression is involved in a regulation of
      lymphocyte and hematopoietic precursor activity.
AB  - A biological function of endogenously expressed MuLV p15E-related proteins for
      lymphocyte and hematopoietic precursor activity in mice was examined. A high
      level of endogenous p15E-related peptide expression in spleen cells of mice with
      hemolytic anemia rendered by phenylhydrazine (PHZ) treatment was observed,
      detected by hyperimmune rabbit antisera against amino acid sequence which compose
      the immunosuppressive domain (ISD) of exogenous viral transmembrane (TM) p15E
      protein. The conditioned medium of these cultured cells (PHZ/CM) was inhibitory
      for lymphocyte blastogenesis and granulocyte-macrophage (GM) precursor activity,
      but stimulatory for the erythroid colony growth. When added to PHZ/CM, anti
      ISD/p15E antibodies were capable to abrogate these effects. These antibodies
      bound 14K and 48K structural peptides contented in PHZ/CM as presumably smaller
      components of env gene products. Given together, the results indicate that
      erythroid immature cells produce proteins appearing in cell culture medium which
      exert p15E-related properties. These peptides are suggested to exert a down
      regulation for both lymphocyte and GM precursor activities, and the colony
      promoting effect towards erythroid compartment cells.

PMID- 7647287
TI  - Viscum album agglutinin-induced aggregation of blood cells and the lectin effects
      on neutrophil function.
AB  - Extracts from mistletoe enjoy a large popularity in central Europe as an
      unconventional treatment modality for cancer, warranting scientific efforts with
      defined components to delineate any potential benefit. The galactose-specific
      lectin from Viscum album (VAA), known to exhibit immunomodulatory and ensuing
      antitumoral capacities in animal model systems, was shown to aggregate human
      blood cells in the following order: neutrophils, mononuclear cells--thrombocytes
      and erythrocytes. To contribute to the analysis of lectin effects on individual
      aspects of the host defence system, two parameters of neutrophils were
      quantitatively assessed, namely the aggregating activity of VAA as a measure of
      strength of interaction with cell surface ligands and the effect of lectin on
      oxidative metabolism (H2O2 release) of these cells. It was found that whole
      lectin and its carbohydrate-binding B-subunit possessed the capacity to induce
      cell aggregation and H2O2 release, which were blocked by D-galactose and lactose.
      Both effects displayed similar dependence on the lectin concentration in the
      range 0.1-25 micrograms/ml. The toxic A-subunit displayed detectable activity
      only in high doses (50 micrograms/ml) while the bovine heart galaptin (14 kDa;
      galectin-1) failed to affect neutrophils. The role of oxidative metabolism in
      regulation of neutrophil aggregation induced by VAA was studied using metabolic
      inhibitors and controlled heating at 46 degrees C leading to inhibition of plasma
      membrane NADPH-oxidase system. Trifluoperazine and menadione inhibited the
      neutrophil aggregation in a dose-dependent manner in comparison with such
      inhibitors as amiloride and theophylline.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7647288
TI  - Myelopeptides: bone marrow regulatory mediators.
AB  - Bone marrow cells of various animal species and men produce a group of
      bioregulatory peptides called myelopeptides (MPs). A highly purified MP fraction
      and some individual molecules have been isolated from the supernatant of porcine
      bone marrow cell cultures by reverse phase chromatography. MPs have a wide
      spectrum of functional activities: immunoregulatory, differentiating and opiate
      like. They evoke 2.5-fold stimulation of antibody production to various antigens.
      They correct some immune defects in MRL/lpr mice with spontaneous autoimmune
      disorders that results in 2-fold prolongation of the life span of these mice. MPs
      influence the differentiation of bone marrow and peripheral blood cells derived
      from healthy and leukemic donors. They induce terminal differentiation in the
      leukemic human HL-60 cell line. MPs also show an effect on pain sensitivity. A
      new immunocorrective drug Myelopid has been developed on the basis of MP
      mixtures. This drug is effectively used in Russia both in medicine and veterinary
      practice for prophylaxis and treatment of diseases accompanied by
      immunodeficiency. Two individual MPs were isolated and identified: Phe-Leu-Gly
      Phe-Pro-Thr (MP-1) and Leu-Val-Val-Tyr-Pro-Trp (MP-2). MP-1 displays
      immunoregulatory activity; MP-2 abolishes the inhibitory effect of leukemic cells
      on T-lymphocyte functional activity. MPs seem to provide not only
      immunoregulation but also to participate in complex interactions between
      different systems in the organism.

PMID- 7647289
TI  - Major organ-specific glycoproteins in isolated brain and kidney membranes
      identified as Na,K-ATPase subunits by combined glycan-, lectin-, and
      immunoblotting.
AB  - In the present work combined glycan-, lectin-, and immunoblotting of isolated
      brain and kidney membranes shows that the alpha and beta subunits of Na,K-ATPase
      are the most abundant glycoproteins. Further, Datura stramonium and Galanthus
      nivalis agglutinins recognize the Na,K-ATPase subunits in a mutually exclusive
      manner in membranes from human, rabbit and rat brain or human, rabbit, rat, pig
      and dog kidney indicating the presence of species-independent organ-typical
      glycoforms. The glycosylation status is not related to the ouabain-sensitivity.
      Taken together, the data reveals organ-specific glycoforms of Na,K-ATPase which
      might have roles for organ identification and recognition.

PMID- 7647290
TI  - Evidence that protein kinase C and mitogen activated protein kinase are not
      involved in the mechanism by which insulin stimulates translation in L6
      myoblasts.
AB  - Insulin stimulated a concentration-dependent increase in protein synthesis in L6
      myoblasts which was significant at 1 nM. This response was not prevented by the
      transcription inhibitor, actinomycin D. The protein kinase C (PKC) inhibitor, Ro
      31-8220, and downregulation of PKC by prolonged incubation of cells with 12-O
      tetradecanoylphorbol-13-acetate (TPA), had no effect on the ability of insulin to
      stimulate protein synthesis whilst completely blocking the response to TPA. In
      contrast, insulin failed to enhance protein synthesis significantly in the
      presence of either ibuprofen, a selective cyclooxygenase inhibitor or rapamycin,
      an inhibitor of the 70 kDa S6 kinase. When cell extracts were prepared and
      assayed for total myelin basic protein kinase activity, a stimulatory effect of
      insulin was not observed until the concentration approached 100-fold (i.e. 100
      nM) that required to elicit increases in protein synthesis. Upon fractionation on
      a Mono-Q column, 100 nM insulin increased the activity of 3 peaks which
      phosphorylated myelin basic protein. Two of these peaks were identified as the 42
      and 44 kDa forms of Mitogen Activated Protein (MAP) kinase by immunoblotting. In
      contrast, 1 nM insulin had no effect on the activity of these peaks. The data
      suggest that physiologically relevant concentrations of insulin do not stimulate
      translation in L6 cells through either PKC or the 42/44 kDa isoforms of MAP
      kinase and that this response is, at least in part, mediated through the
      activation of the 70 kDa S6 kinase by cyclooxygenase metabolites.

PMID- 7647291
TI  - Cholesterol enhances cationic liposome-mediated DNA transfection of human
      respiratory epithelial cells.
AB  - Cationic liposome transfection reagents are useful for transferring
      polynucleotides into cells, and have been proposed for human pulmonary gene
      therapy. The effect of adding cholesterol to cationic lipid preparations has been
      tested by first formulating the cationic lipid N-[1-(2,3-dioleoyloxy)propyl-N-[1
      (2-hydroxy)ethyl]-N,N-dimethyl ammonium iodide (DORI) with varying amounts of
      dioleoylphosphatidylethanolamine (DOPE) and cholesterol. Cholesterol was found to
      enhance lipid-mediated transfection in both the respiratory epithelial cells and
      mouse fibroblasts. These findings will facilitate nucleic acid transfection of
      many cell types including differentiated epithelial cell monolayers, and
      therefore may be useful for examining gene regulation in various cell types and
      for developing pulmonary gene therapy.

PMID- 7647292
TI  - NMR study of the selective inhibition of water permeability of rat erythrocyte
      membrane.
AB  - The inhibition of water diffusion across the rat erythrocyte membrane was studied
      by NMR using two basically different types of inhibitory agents: PCMB and in vivo
      irradiation. The contribution of lipid and protein to water permeability revealed
      the inhibitory effect of each pathway. Internal contamination with tritium (25
      115 mGy) reduces water permeability due to protein modifications; for doses
      higher than 100 mGy the lipid mediated mechanism seems also to be impaired. The
      same procedure enables one to assess the extent to which the higher water
      permeability of rat, compared to human, erythrocyte is due to one of the two
      pathways.

PMID- 7647293
TI  - Cis-acting elements and expression pattern of the spinach rps22 gene coding for a
      plastid-specific ribosomal protein.
AB  - In order to study the regulation of nuclear genes coding for plastid ribosomal
      proteins, we have analysed the promoter region of spinach rps22 using both in
      vitro and in vivo approaches. By footprinting analyses, we have identified eight
      DNA elements interacting with spinach leaf nuclear factors in the 300 bp promoter
      region upstream of the transcription start site. Among these elements, four are
      short AT-rich sequences and one is identical to the Hex motif characterized
      initially in wheat histone genes. In transgenic tobacco plants, the reporter gene
      coding for the beta-glucuronidase (GUS) directed by a 1.2 kb upstream region of
      rps22 was expressed in several plant organs, with high levels in leaf mesophyll,
      embryo cotyledons and root meristematic cells and very low levels in other cell
      types. Interestingly, when deleted to -295, the promoter, which contained all the
      foot-printed elements, was still able to confer the same expression pattern,
      although the activity was relatively lower than with the 1.2 kb promoter. When
      deleted further to -154, the promoter, from which the AT-rich elements were
      eliminated, loses its activity almost completely, suggesting that these AT-rich
      elements are important for the rps22 promoter activity. Altogether, our results
      show that rps22 gene expression is controlled by specific cis elements not
      present in other nuclear-encoded plastid ribosomal protein genes studied so far.

PMID- 7647294
TI  - Promoters from kin1 and cor6.6, two homologous Arabidopsis thaliana genes:
      transcriptional regulation and gene expression induced by low temperature, ABA,
      osmoticum and dehydration.
AB  - The Arabidopsis thaliana genes kin1 and cor6.6 belong to the same family and were
      expressed at higher levels following low temperature and ABA treatments. In an
      attempt to elucidate the mechanism of gene regulation by low temperature, the
      relationship between low-temperature- and abscisic acid (ABA)-induced gene
      expression and possible differential expression of the two genes, we have cloned
      a 5.3 kb genomic fragment harboring kin1 and cor6.6 and their respective 5'
      sequences. The putative promoters of both genes were fused to the beta
      glucuronidase (GUS) coding sequence and GUS expression was analysed in transgenic
      tobacco and Arabidopsis plants. The cor6.6 promoter produced a higher basal level
      of expression than the kin1 promoter in transgenic tobacco. Enzyme assays of
      inducible GUS activity in transgenic Arabidopsis and tobacco plants showed that
      GUS activity directed by both kin1 and cor6.6 promoters was significantly induced
      by ABA, dehydration and osmoticum, but not by low temperature. Northern analysis
      revealed, in contrast, that GUS mRNA was significantly induced in these
      transgenic plants by low temperature. Further analysis showed that, at low
      temperature, GUS protein synthesis from the induced GUS mRNA was inhibited.
      Together these results reveal induction of kin1 and cor6.6 transcription by low
      temperature, exogenous ABA and dehydration. However, low-temperature expression
      is dramatically reduced at the translational level.

PMID- 7647295
TI  - Promoters from kin1 and cor6.6, two Arabidopsis thaliana low-temperature- and ABA
      inducible genes, direct strong beta-glucuronidase expression in guard cells,
      pollen and young developing seeds.
AB  - The ability of most higher plants to withstand freezing can be enhanced by cold
      acclimation, although the freezing tolerance of plant tissues is also affected by
      their developmental stage. In addition, low temperature has pleiotropic effects
      on many plant developmental processes such as vernalization. The interaction
      between plant development and low temperature implies that some genes are
      regulated by both environmental factors and developmental cues. Although a number
      of cold-inducible genes from plants have been identified, information concerning
      their regulation during plant development is limited. In order to understand
      their developmental regulation and obtain possible clues as to function, the
      promoters of kin1 and cor6.6, two cold- and abscisic acid (ABA)-regulated genes
      from Arabidopsis thaliana, were fused to the beta-glucuronidase (GUS)-coding
      sequence and the resulting constructs were used to transform tobacco and A.
      thaliana. Transgenic plants with either the kin1 or cor6.6 promoter showed strong
      GUS expression in pollen, developing seeds, trichomes and, most interestingly, in
      guard cells. During pollen development, maximum GUS activity was found in mature
      pollen. In contrast, the maximum GUS activity during seed development was during
      early embryogenesis. These patterns of expression distinguish kin1 and cor6.6
      from related lea genes which are strongly expressed during late embryogenesis.
      There was no major qualitative difference in patterns of GUS expression between
      kin1 and cor6.6 promoters and the results were similar for transgenic tobacco and
      Arabidopsis. Considering the results described, as well as those in an
      accompanying paper (Wang et al., 1995, Plant Mol Biol 28: 605-617 (this issue),
      we suggest that osmotic potential might be a major factor in regulating the
      expression of kin1 and cor6.6 during several developmental processes. The
      implication of the results for possible function of the gene products is
      discussed.

PMID- 7647296
TI  - Characterization of the nuclear gene encoding mitochondrial aconitase in the
      marine red alga Gracilaria verrucosa.
AB  - We have cloned a nuclear gene from the marine red alga Gracilaria verrucosa that
      encodes the complete 779 amino-acid mitochondrial aconitase (m-ACN), the first
      characterized from a photosynthetic organism. The N-terminal 28 deduced amino
      acids are predicted to constitute the mitochondrial transit peptide, the first
      described from a red alga. Putative transcriptional cis-acting elements were
      identified in the upstream untranslated region. The G. verrucosa m-ACN gene (m
      ACN) is present in a single copy and is located ca. 1.5 kb upstream from the
      single-copy polyubiquitin gene. The single spliceosomal intron is located near
      the 5' end of the region encoding the mature m-ACN in precisely the same location
      and phase as intron 2 in Caenorhabditis elegans m-ACN; sequences at its 3' and 5'
      splice junctions and at the predicted lariat branch point conform well to the
      eukaryote consensus sequences. Multiple protein-sequence alignment of m-ACN,
      bacterial aconitase (b-ACN) and iron-responsive element-binding protein (IRE-BP),
      and phylogenetic analyses, revealed that m-ACN does not share a recent common
      ancestry with either b-ACN or IRE-BP.

PMID- 7647297
TI  - Cloning of a tomato polygalacturonase expressed in abscission.
AB  - Abscission, organ separation, is accompanied by cell wall breakdown in separation
      layer cells. In tomato (Lycopersicon esculentum), ethylene-induced abscission is
      correlated with an increase in polygalacturonase (PG) and endo-beta-1,4-D
      glucanase (cellulase) activity. We have identified a putative, abscission
      specific cDNA clone for PG, pTAPG1. The TAPG1 cDNA has 43% identity at the amino
      acid level with the tomato fruit PG. Genomic blot analysis suggests that the gene
      for TAPG1 is a member of a small subfamily of PG genes that is distinct from the
      tomato fruit PG. The TAPG1 cDNA hybridizes to mRNA expressed during the course of
      ethylene-induced leaf and flower abscission. A high level of PG transcript
      accumulation coincides with the occurrence of abscission. Auxin, an abscission
      inhibitor, and silver thiosulfate, an ethylene action inhibitor, suppressed
      accumulation of mRNA in leaf abscission zones complementary to the TAPG1 cDNA.
      Expression of TAPG1 transcripts is several-fold higher in flower abscission zones
      than in leaf abscission zones. The identification of cDNAs that encode abscission
      specific PG provide and additional tool to study the regulation of abscission and
      cell wall dissolution in separation layer cells.

PMID- 7647298
TI  - Primary structure of the plasma membrane H(+)-ATPase from the halotolerant alga
      Dunaliella bioculata.
AB  - P-type ATPase-specific oligodeoxyribonucleotides were used to obtain a fragment
      of the H(+)-ATPase of the salt tolerant alga Dunaliella bioculata by polymerase
      chain reaction (PCR). This fragment served as a probe in screening a cDNA-library
      from this organism. The complete primary structure of the ATPase protein (DBPMA1)
      was deduced from sequencing a 4.7 kb cDNA clone. The protein shows highest
      homology to H(+)-ATPases from higher plants and fungi (43% identity, 67%
      similarity) but has a higher calculated molecular mass (123 kDa). The latter can
      be assigned mainly to an additional hydrophilic domain between transmembrane
      segments VI and VII and to an extended carboxyterminus. These unusual structural
      features of DBPMA1 are interpreted in terms of providing regulatory sites of the
      enzyme. Southern blot analysis suggests the presence of only a single copy of the
      gene in the haploid D. bioculata genome. To investigate the role of the H(+)
      ATPase in the adaption of D. bioculata to different external NaCl concentrations,
      we employed northern blot analyses. The results indicate that the pma1 transcript
      level of cells growing in salinities between 0.1 and 3 M NaCl is not directly
      correlated with the external salt concentration.

PMID- 7647299
TI  - Intron-dependent transient expression of the maize GapA1 gene.
AB  - Transient expression experiments show that the maize GapA1 promoter exhibits a
      requirement for sequences contained within intron 1 and surrounding exon border
      regions for expression in maize Black Mexican Sweet cells. Maize GapA1-promoter
      constructs lacking intron 1 are inactive. Intron 1 and its exon border sequences,
      when reintroduced into constructs lacking introns, restore gene activity whereas
      intron 2 and its exon borders to not. The minimal promoter so defined encompasses
      roughly 250 bp upstream of the in vivo transcription start and appears also to
      include intron 1. An octameric sequence was identified in intron 1 of maize GapA1
      which is similar to sequence motifs found in other maize introns known to
      increase transient expression. Partial restoration of gene expression in GapA1
      constructs lacking intron 1 was achieved through insertion of the identified
      octameric sequence.

PMID- 7647300
TI  - Molecular cloning of two tandemly arranged peroxidase genes from Populus
      kitakamiensis and their differential regulation in the stem.
AB  - A genomic library was prepared from Populus kitakamiensis and screened with the
      cDNA for an anionic peroxidase from P. kitakamiensis. One genomic clone was
      isolated that contained two tandemly oriented genes for anionic peroxidases,
      prxA3a and prxA4a. Both genes consisted of four exons and three introns; the
      introns had consensus nucleotides, namely, GT and AG, at their 5' and 3' ends,
      respectively. The prxA3a and prxA4a genes encoded 347 and 343 amino acid
      residues, respectively, including putative signal sequences at the amino-termini.
      Putative promoters and polyadenylation signals were found in the flanking regions
      of both genes. The sequence of the coding region of prxA3a was completely
      identical to that of the cDNA clone pA3, whereas the sequence of the coding
      region of prxA4a was only 73% identical to that of the cDNA clone pA3. Northern
      blot analysis showed that the patterns of expression of the mRNAs that
      corresponded to prxA3a and prxA4a differed in stems of P. kitakamiensis.

PMID- 7647301
TI  - Nature and regulation of pistil-expressed genes in tomato.
AB  - The specialized reproductive functions of angiosperm pistils are dependent in
      part upon the regulated activation of numerous genes expressed predominantly in
      this organ system. To better understand the nature of these pistil-predominant
      gene products we have analyzed seven cDNA clones isolated from tomato pistils
      through differential hybridization screening. Six of the seven cDNAs represent
      sequences previously undescribed in tomato, each having a unique pistil- and/or
      floral-predominant expression pattern. The putative protein products encoded by
      six of the cDNAs have been identified by their similarity to sequences in the
      database of previously sequenced genes, with a seventh sequence having no
      significant similarity with any previously reported sequence. Three of the
      putative proteins appear to be targeted to the endomembrane system and include an
      endo-beta-1,4-glucanase which is expressed exclusively in pistils at early stages
      of development, and proteins similar in sequence to gamma-thionin and miraculin
      which are expressed in immature pistils and stamens, and in either sepals or
      petals, respectively. Two other clones, similar in sequence to each other, were
      expressed primarily in immature pistils and stamens and encode distinct proteins
      with similarity to leucine aminopeptidases. An additional clone, which encodes a
      protein similar in sequence to the enzyme hyoscyamine 6-beta-hydroxylase and to
      other members of the family of Fe2+/ascorbate-dependent oxidases, was expressed
      at high levels in pistils, stamens and sepals, and at detectable levels in some
      vegetative organs. Together, these observations provide new insight into the
      nature and possible functional roles of genes expressed during reproductive
      development.

PMID- 7647302
TI  - Cloning and characterization of two cDNA clones encoding seed-specific
      antimicrobial peptides from Mirabilis jalapa L.
AB  - We have isolated and characterized two cDNA clones (designated MJ1 and MJ2)
      encoding the two Mirabilis jalapa antimicrobial peptides (Mj-AMP1 and Mj-AMP2,
      respectively), which were previously purified from seeds of this plant species
      (Cammue et al. (1992), J Biol Chem 267: 2228-2233). In both cases, the deduced
      amino acid sequences reveal the presence of a putative signal sequence preceding
      the mature peptide, indicating that the Mj-AMPs are expressed as preproteins. The
      Mj-AMP1- and Mj-AMP2-encoding genes are interrupted in their coding sequences by
      a single intron (380 bp and 900 bp for Mj-AMP1 and Mj-AMP2 genes, respectively).
      Southern blot analysis indicates that the Mj-AMP-encoding genes belong to a gene
      family of low complexity. Northern blot analysis suggests seed-specific
      expression of Mj-AMPs since transcripts of the expected size could only be
      detected in near-mature and in mature seeds of M. jalapa.

PMID- 7647303
TI  - The homeobox gene ATK1 of Arabidopsis thaliana is expressed in the shoot apex of
      the seedling and in flowers and inflorescence stems of mature plants.
AB  - The homeodomain is a DNA-binding domain present in a large family of eukaryotic
      regulatory proteins. Homeodomain proteins have been shown to play key roles in
      controlling developmental programs in various organisms. Here we report the
      isolation and characterisation of a homeobox gene from Arabidopsis thaliana
      designated ATK1. The gene was isolated using as a probe the homeobox domain of
      the KN1 gene from maize. The homeodomain of ATK1 is highly homologous to the
      homeodomain of the KN1 gene of maize (81%) but shows only poor homology outside
      the homeodomain. Therefore ATK1 is probably not the Arabidopsis homologue of the
      KN1 gene from maize. It contains the four invariant amino acid residues present
      in the recognition helix 3 of all other homeodomain proteins. Outside the
      homeodomain a region rich in aspartate and glutamate residues is found suggesting
      that ATK1 is a transcriptional activator. The gene contains four introns which is
      similar in the KN1 gene of maize and the Osh1 gene of rice. Primer extension
      reveals the presence of two transcription initiation sites. The leader sequence
      of the genuine transcript is 342 nucleotides long and contains two upstream open
      reading frames. ATK1 is strongly expressed in the shoot apex of seedlings, while
      in mature plants the gene is primarily expressed in flowers and inflorescence
      stems. Such an expression pattern is reminiscent of that of the KN1 gene of maize
      and therefore ATK1 could similarly be involved in determining cell fate.

PMID- 7647305
TI  - Translational arrest in hypoxic potato tubers is correlated with the aberrant
      association of elongation factor EF-1 alpha with polysomes.
AB  - Translation elongation factor EF-1 alpha became stably associated with potato
      tuber polysomes at the onset of hypoxia, coincident with a sharp rise in lactate
      and decrease in tissue pH. This aberrant association of EF-1 alpha with polysomes
      also occurred when aerobic tuber extracts were acidified in vitro. Upon
      resumption of protein synthesis, an increase in the steady-state levels of EF-1
      alpha, and expression of an EF-1 alpha/GUS transgene was observed. These results
      indicate that translational arrest results from to the failure of EF-1 alpha to
      dissociate from ribosomes during the elongation cycle, and that restoration of
      protein synthesis is coordinated with expression of EF-1 alpha.

PMID- 7647304
TI  - Aerobic fermentation in tobacco pollen.
AB  - We characterized the genes coding for the two dedicated enzymes of ethanolic
      fermentation, alcohol dehydrogenase (ADH) and pyruvate decarboxylase (PDC), and
      show that they are functional in pollen. Two PDC-encoding genes were isolated,
      which displayed reciprocal regulation: PDC1 was anaerobically induced in leaves,
      whereas PDC2 mRNA was absent in leaves, but constitutively present in pollen. A
      flux through the ethanolic fermentation pathway could be measured in pollen under
      all tested environmental and developmental conditions. Surprisingly, the major
      factor influencing the rate of ethanol production was not oxygen availability,
      but the composition of the incubation medium. Under optimal conditions for pollen
      tube growth, approximately two-thirds of the carbon consumed was fermented, and
      ethanol accumulated into the surrounding medium to a concentration exceeding 100
      mM.

PMID- 7647306
TI  - Cloning and sequencing of the nitrate transport system from the thermophilic,
      filamentous cyanobacterium Phormidium laminosum: comparative analysis with the
      homologous system from Synechococcus sp. PCC 7942.
AB  - A genomic region from the filamentous, thermophilic non-N2-fixing cyanobacterium
      Phormidium laminosum was cloned and sequenced. It includes the nitrite reductase
      gene (nirA) and three other genes (nrtA, B and C) located downstream of nirA,
      which are related to the nitrate transport system on the basis of a comparison
      with the homologous system from Synechococcus sp. PCC 7942. No additional nitrate
      assimilation-related genes were identified in about 5 kb sequenced downstream of
      nrtC. All four genes are arranged as an operon with a promoter-like region
      upstream of the nirA gene. Transcripts of these nitrate assimilation genes
      accumulated after long periods of nitrogen starvation. This operon also contains
      inverted repeat sequences in the intercistronic regions which might be involved
      in mRNA processing or stability.

PMID- 7647307
TI  - Regulation of the cell cycle by viral oncoproteins.
AB  - Human papillomavirus (HPVs) adenovirus and simian virus 40 (SV40) are small DNA
      viruses which can show oncogenic activity. Although not otherwise related, all
      three have adopted very similar strategies to deregulate cell growth; each virus
      encoding oncoproteins which interact with the same cellular targets. Of
      particular interest are the interactions with the cell encoded pRB and p53
      proteins, products of tumour suppressor genes. Somatic mutation results in the
      loss of the pRB and p53 function in many cancers and the contribution of the
      viruses to tumour development appears to reflect their ability to inactivate
      these cellular proteins. Both pRB and p53 negatively regulate progress through
      the cell cycle and the action of the viral proteins has highlighted the central
      importance of these tumour suppressor proteins in maintaining normal cell growth.

PMID- 7647308
TI  - Cyclins, CDKs and cancer.
AB  - The connections between cancer and the basic machinery of the cell cycle have
      taken a surprisingly long time to become apparent. However, the past 2 years has
      seen a dramatic increase in the number of cell cycles regulators that have been
      implicated as either protooncogenes or as tumour suppressor genes. In this review
      I will attempt to show how perturbations in the known cell cycle regulators may
      play a part in the process of oncogenesis.

PMID- 7647309
TI  - Cyclin D1 as a cellular proto-oncogene.
AB  - Deregulated expression of cyclin D1 occurs in several types of human cancer.
      Since it often results from a specific chromosomal abnormality, this over
      expression is likely to be significant in the development of the disease. Cyclin
      D1 is also implicated in virally induced tumors in mice and transgenic models
      based on ectopic expression if cyclin D1 recapitulate features of the naturally
      occurring tumors. By these criteria, as well as its effects in transfected rodent
      cells, cyclin D1 has the hallmarks of a cellular proto-oncogene. Although the
      normal role of cyclin D1 is not well understood, its oncogenic properties appear
      to involve functional interactions with cyclin-dependent kinases, the
      retinoblastoma gene product and the MTS1/p16 tumor suppressor gene.

PMID- 7647310
TI  - The retinoblastoma protein and its relatives.
AB  - The retinoblastoma tumor suppressor gene is inactivated in retinoblastomas and a
      variety of other tumor types. In addition, it is one of several cellular proteins
      targeted by the transforming proteins of the small DNA tumor viruses. At least
      two other cellular proteins that are targeted by the viral transforming proteins
      are structurally and functionally related to the protein encoded by the
      retinoblastoma tumor suppressor gene. Recent data has described a complex series
      of interactions with cyclins, kinases and transcription factors. It is presumably
      through these interactions that the retinoblastoma-related proteins exert their
      effects on cellular proliferation.

PMID- 7647311
TI  - Transcriptional control by the retinoblastoma protein.
AB  - The retinoblastoma gene product is an abundant nuclear protein whose 'pocket
      domain' mediates numerous protein-protein interactions. A substantial proportion
      of the RB-interacting proteins are transcription factors suggesting that RB plays
      a fundamental role in the regulation of transcription. Via these interactions, RB
      can influence both the progression through the cell cycle and the expression of
      lineage specific products. In this review I discuss some of the likely mechanisms
      by which RB regulates cell proliferation and differentiation.

PMID- 7647312
TI  - Transcriptional control by E2F.
AB  - Considerable evidence suggests that the E2F/DRTF1 family of transcription factors
      (hereafter referred to as 'E2F') plays a critical role in cell growth control.
      For example, the ability of several small DNA tumour viruses, such as SV40,
      adenovirus and human papillomavirus, to transform certain cells is tightly linked
      to their ability to deregulate E2F. Furthermore, E2F appears to directly regulate
      the transcription of a diverse set of genes implicated in DNA replication and
      cell growth control. Finally, a number of known cell cycle regulators, some of
      which are commonly mutated in human tumours, appear to exert their effects, at
      least in part, by altering E2F activity. Among these are pRb, p53, cdk-2, cdk-4
      and certain cyclins.

PMID- 7647313
TI  - 9th International Congress of Biorheology and 2nd International Conference of
      Clinical Hemorheology. Big Sky, Montana, July 23-28, 1995. Abstracts.

PMID- 7647314
TI  - Carpal tunnel syndrome: etiological, clinical and electrophysiological aspects of
      262 cases.
AB  - Two hundred and sixty-two patients with carpal tunnel syndrome (CTS) were
      analyzed retrospectively. Results showed that middle- and older-age women were
      more apt to have CTS than men, and that the dominant hand was more frequently
      affected. Hormonal changes, repetitive and forceful movements, awkward positions
      of hand and wrist, and other factors may be associated with CTS. Typical clinical
      manifestations include pain and paresthesia in the median nerve territory,
      worsening at night or in the early morning, and being relieved by shaking the
      hand. Although the patients may localize the discomfort beyond the territory,
      sensory changes are variable and not entirely reliable. Conduction abnormalities
      often appeared selectively in the median nerve distal to the wrist in CTS. If the
      patient who is clinically suggestive of CTS shows normal conduction with
      conventional methods, palmar stimulation and inching technique is recommended.
      The diagnosis of CTS requires confirmation of illness history, symptoms and signs
      with objective electrodiagnostic tests.

PMID- 7647315
TI  - Surgical treatment of hallux valgus by reconstruction of metatarsal arch and
      modified McBride operation (40 cases report).
AB  - 72 feet with hallux valgus among 40 patients treated by reconstruction of
      metatarsal arch and modified McBride operation are reported in this paper. After
      an average of 4.5 years of postoperative follow-up, the results showed an overall
      9 degrees and 3 degrees correction of the hallux abductus angle and the
      intermetatarsal angle, respectively. 95% of the cases of bunions disappeared, 66%
      calli under the heads of the first and second metatarsal disappeared, and 91%
      patients were satisfied with the changes of their feet appearance.

PMID- 7647316
TI  - Irrigation and traction therapy for open fracture with large-sized full-thickness
      skin-deficit and severely infected wound.
AB  - In this paper the results of skeletal traction and irrigation therapy (STIT) used
      for open fracture complicated with large-sized full-thickness skin-deficit and
      infection wounds (OFIW) were presented. Fourteen patients of OFIW were treated by
      the plaster cast and wound dressing (PCWD), and 30 patients of OFIW were treated
      by STIT. The results indicated that after one week of treatment, the white blood
      cell count in the STIT group, compared to 17.6 +/- 1.0 x 10(9)/L from before
      treatment, returned to 8.8 +/- 0.8 x 10(9)/L, and in contrast, the cell count of
      the PCWD group was about 13.0 +/- 1.4 x 10(9)/L. All of wound exudate culture in
      the STIT group was negative, and those of 7 cases (7/14) in PCWD group were
      positive (P < 0.01). The symptoms and signs such as pain, fever and septic
      exudate on the wound in the STIT group were much milder than those in the PCWD
      group. There were 5 cases (35.7%) of toxicemia and septicemia, 2 cases (14.3%) of
      osteomyelitis, 2 cases (14.3%) of amputation, 1 case (7.1%) of delayed union and
      3 cases (21.4%) of malunion in the PCWD group, and no complications in the STIT
      group.

PMID- 7647317
TI  - The effect of posterior element resection on the stress distribution in the
      lumbar spine.
AB  - A three-dimensional finite element model of the lumbar motion segment was used to
      predict the stress distribution in lumbar spine with posterior element resection.
      It was shown that the stress level in all parts of the lumbar spine was elevated
      although the stress distribution remained unchanged. The authors concluded that
      the posterior element resection in lumbar surgery should be avoided as much as
      possible.

PMID- 7647318
TI  - A clinical and neuroelectrophysiological study of hyperkalemic periodic
      paralysis.
AB  - A case of atypical hyperkalemic periodic paralysis is reported. The diagnosis was
      confirmed by hyperkalemic test, cold water test, and differentiation of attack
      period and rest period by the measurement of motor nerve conduction amplitude.
      Etio-pathology of this disease is discussed from the view of
      neuroelectrophysiology.

PMID- 7647319
TI  - An unusual case of asymptomatic aplastic renal dysplasia.
AB  - The postmortem examination of a 59-year-old man who had suffered from acute
      abdominal pain for two days revealed that the cause of death was peritonitis
      secondary to perforated peptic ulceration. During examination, it was found that
      the urinary tract was abnormal. Here, we report a postmortem finding of aplastic
      renal dysplasia of the kidney and malformation of the urinary tract.

PMID- 7647320
TI  - The association of polymorphisms at a VNTR locus 3' to the apolipoprotein B gene
      with coronary heart disease in Chinese population.
AB  - The polymorphisms of variable number of tandem repeats (VNTR) 3' to the
      apolipoprotein B (apo B) gene were investigated using polymerase chain reaction
      (PCR) in a sample of 103 patients with documented coronary heart disease (CHD)
      and 100 healthy individuals selected from Chinese Han nationality. Twelve
      segregating alleles (3' beta 29-51) were observed in the pooled total of 203
      subjects. The most common allele was 3' beta 37, followed by 3' beta 39 with
      frequencies of 0.362 and 0.296, respectively. This model of allele distribution
      was coincident with the results form different ethnic groups, but the relative
      frequencies of alleles were different. In comparison with the allele frequencies
      between the patients and controls, alleles bigger than 3' beta 39 (3' VNTR-B)
      were significantly more common among the patients than among the controls (P <
      0.001). Moreover, in the CHD group patients with plasma levels of TC > or = 3.88
      mmol/L, LDL-C > or = 2.59 mmol/L and HDL-C < 1.16 mmol/L had significantly higher
      frequencies of 3' VNTR-B allele (P < 0.01). Therefore, it is suggested that 3'
      VNTR-B allele might be involved in the development of coronary atherosclerosis,
      presumably through their influences on lipid metabolism.

PMID- 7647321
TI  - An association study between essential hypertension and HLA-DRB1 alleles.
AB  - It is well established that genetic and environmental factors are involved in the
      etiology of essential hypertension (EH). Previous studies have suggested that at
      least one of the HLA genes is responsible for the genetic susceptibility to EH.
      Our aim in the present study was to investigate this issue in China by the PCR
      SSP HLA-DRB1 typing method. The results showed an increased frequency of HLA-DR2
      and a decreased frequency of HLA-DR7 with EH patients compared with controls. We
      consider that HLA-DR2 may represent a marker for susceptibility to EH in the
      North Chinese population.

PMID- 7647322
TI  - Lipopolysaccharide induces exposure of fibrinogen receptors on human platelets.
AB  - The effect of lipopolysaccharide (LPS) on the exposure of platelet fibrinogen
      receptors was investigated. The results showed that: 1) LPS increased the binding
      of fibrinogen-gold complexes to platelets and the labels were primarily limited
      to shape-changed platelets; 2) LPS caused a dose-dependent rise in intracellular
      Ca2+ concentration in platelets; 3) LPS induced the activation of platelet
      protein kinase C (PKC) and the phosphorylation of glycoprotein llla (GPllla)
      which was inhibited by H-7. All these results suggest that stimulation of
      platelets with LPS causes a conformational change in glycoprotein llb/llla
      (GPllb/llla) through platelet shape change and/or phosphorylation of GPllla via
      PKC, which serves to expose the fibrinogen binding sites of GPllb/llla on human
      platelets.

PMID- 7647323
TI  - Comparison of four methods to generate immunoreactive fragments of a murine
      monoclonal antibody OC859 against human ovarian epithelial cancer antigen.
AB  - In the present study, four different proteases (pepsin, papain, bromelain and
      ficin) were screened with a murine monoclonal antibody OC859, in order to verify
      whether different digestion procedures could improve yield and stability of the
      F(ab')2 or Fab fragments. The yields of F(ab')2 or Fab fragments from digestion
      with pepsin, papain, bromelain and ficin were respectively 20.3 +/- 2.0%, 50.5 +/
      5.0%, 74.4 +/- 2.7% and 82.8 +/- 10.2% of the theoretical maximum.
      Immunoreactivity in a noncompetitive solid-phase radioimmunoassay (SPRIA) of the
      fragments generated by the four proteases were respectively 10 +/- 5%, 36 +/- 5%,
      60 +/- 6% and 75 +/- 6% of the intact OC859 IgG. These results suggested that the
      fragmentation of OC859 with ficin gave a higher yield of superior immunoreactive
      fragments.

PMID- 7647324
TI  - Variation in membrane properties from the action of laminin on membrane
      receptors.
AB  - Biophysical studies were conducted on the action of laminin through membrane
      receptors of cancer cells. The results showed that variations occurred in the
      thermodynamic properties of membrane proteins, the mobility of hydrocarbon chains
      of membrane lipids, and the permeability and transportation pathways of the
      membrane.

PMID- 7647325
TI  - Changes of immune functions after radiation, burns and combined radiation-burn
      injury in rats.
AB  - The changes of several immune functions were observed in rats after they were
      inflicted with 6 Gy gamma rays irradiation, 15% TBSA full thickness brun and the
      combination of the 2 injuries. It was found that the functions of thymocytes and
      splenoctyes suffered the most severe suppression in the 24th to 72nd hour after
      radiation injury and began to recover on the 7th day. In the rats with burn
      injury, the suppression on thymocytes and splenocytes were significantly less
      severe than that after radiation and recovered more rapidly. The effects of
      combined radiation-burn injury showed several characteristics. The suppression on
      the thymocytes was more severe with slower recovery as compared with that after
      single radiation injury only. The suppression on the splenocytes as a whole was
      similar to that after single radiation injury, but in the early stage after
      combined injury, the suppression was far more severe than that after radiation.
      Escharectomy and skin grafting on the burn wounds on the 1st day after combined
      injury could accelerate the recovery on both the thymocytes and splenocytes. Our
      findings indicated that the severity of the suppression on the immune functions
      due to combined radiation-burn injury might depend on the size of the burn
      wounds.

PMID- 7647326
TI  - A complex of intermediate filament protein-DNA: a target for autoantibodies in
      systemic lupus erythematosus?
AB  - Autoantibodies in systemic lupus erythematosus which cross-react with double
      stranded DNA and intermediate filament proteins are frequently reported. However,
      little is known about the origin and the target of these antibodies. In this
      paper, a polyspecific monoclonal antibody, XY12, produced by the immunization of
      genetically non-autoimmune mice with a DNA-protein complex is detailed. Its
      antigen binding patterns are very similar to the autoantibodies. The data suggest
      that these autoantibodies may be triggered by a circulating nucleoprotein.

PMID- 7647327
TI  - Borrelia burgdorferi DNA in biological samples from patients with sarcoidosis
      using the polymerase chain reaction technique.
AB  - Polymerase chain reaction (PCR) was used to detect the presence of Borrelia
      burgdoferi DNA in biological samples from patients with sarcoidosis. The target
      DNA sequence was of chromosomal origin. The amplified DNA sequence was analyzed
      by agarose gel electrophoresis, PAGE with silver staining, and the identity of
      amplified DNA was confirmed by restriction enzyme cleavage and DNA-DNA
      hybridization with a 32P-labelled probe. The assay was sensitive to fewer than
      two copies of B. burgdorferi genome, even in the presence of a 10(4)-fold excess
      of human eukaryotic DNA, and was also specific to different B. burgdorferi
      strains tested. Sera serologically positive to B. burgdorferi (n = 26),
      bronchoalveolar lavage fluid and supernatant of BALF (n = 26) and peripheral
      blood (n = 9) from sarcoidosis patients were tested. The positive rate was low
      (4/26, 2/26, and 0/9, respectively). It was considered that DNA from B.
      burgdorferi may be identified in a minority of patients with sarcoidosis, and it
      may play a pathogenetic role in such cases. More studies need to be done before
      advancing the hypothesis of an etiologic role of B. burgdorferi in sarcoidosis.

PMID- 7647328
TI  - Endovascular embolization treatment of cerebral arteriovenous malformations
      (report of 54 cases).
AB  - For further research on endovascular embolization treatment of AVMs, 54 patients
      with AVMs treated with embolization were observed. It was found that embolization
      was an effective procedure for the treatment of AVMs. Combined treatment of AVMs
      with presurgical embolization and direct surgery could reduce the complications
      resulting from large and high flow AVMs with lone surgical removal.

PMID- 7647329
TI  - Immunohistochemical determination of pS2 in invasive breast carcinomas: a study
      on 942 cases.
AB  - To assess the practical prognostic value of pS2, we evaluated its expression by
      immunohistochemistry in paraffin-embedded tissue from 942 previously untreated
      invasive ductal carcinomas (IDC) resected in our center between 1980 and 1986.
      Positive staining of tumor cells was found in 684 cases (73%), but most of the
      tumors contained only a small amount of positive cells. There was a negative
      correlation between pS2 and tumor size (p = 0.01) and histological grade (p <
      0.0001), and a positive correlation between pS2 and hormonal receptor status (p <
      0.001). With respect to overall survival, pS2 positivity was associated with a
      better prognosis for the whole group and the node-positive sub-group. However, in
      terms of relapse and metastasis, pS2 was not significant. Furthermore, in
      multivariate analysis including tumor size, nodal status, histological grade, ER
      status, PR status, chemotherapy, hormonal treatment, and pS2, the latter appears
      to be of no prognostic value.

PMID- 7647330
TI  - Obesity and subcutaneous fat patterning in relation to survival of postmenopausal
      breast cancer patients participating in the DOM-project.
AB  - The effect of obesity and fat distribution on survival of breast cancer patients
      was studied prospectively in 241 women with a natural menopause who participated
      in a breast cancer screening project, the DOM-project in Utrecht, The
      Netherlands. Mean follow-up time was 9.1 years and endpoint of interest was death
      from breast cancer. Fat distribution was assessed by contrasting groups of
      subscapular and triceps skinfold thickness. No significant differences in
      survival time between more obese (Quetelet's index > or = 26 kg/m2) and leaner
      (Quetelet's index < 26 kg/m2) patients or between patients with central fat
      distribution and patients with peripheral fat distribution were observed.
      Analyses were stratified by axillary node status, estrogen receptor status, and
      way of detection (by first screening or afterwards). Results of the stratified
      analyses were suggestive of a modifying effect of these factors. The absence of
      an association between obesity and survival time might be explained by two
      counteracting mechanisms. On the one hand obesity might be related to impaired
      survival, due to a tumor growth promoting effect of extra-ovarian estrogens. On
      the other hand obesity might be related to improved survival in a screened
      population, because obese patients profit more from screening by earlier
      detection of tumors than leaner counterparts.

PMID- 7647331
TI  - Transformation of estrone and estradiol in hormone-dependent and hormone
      independent human breast cancer cells. Effects of the antiestrogen ICI 164,384,
      danazol, and promegestone (R-5020).
AB  - Using different hormone-dependent (MCF-7, T-47D) and hormone-independent (MDA-MB
      231, Hs-578S, MDA-MB-436) human breast cancer cells, the interconversion estrone
      (E1)<-->estradiol (E2) was explored. The data show very clearly that in the
      hormone-dependent cells the tendency is to form E2 after incubation with E1,
      whereas after incubation with E2 most of this estrogen remains unchanged. In the
      hormone-independent cells, in contrast most of E1 remains E1, while E2 is
      converted into E1. The tendency of the reductive<-->oxidative direction is
      supported by the analysis of estrogens in the culture medium. To explore the
      possible action of different drugs on the 17 beta-hydroxysteroid dehydrogenase
      (17 beta-HSD) activity, it was observed that the potent antiestrogen ICI 164,384
      inhibits the conversion of E1 to E2, while a lesser effect is observed with
      Danazol and only weak inhibition is obtained with the progestagen Promegestone (R
      5020). It is concluded that the orientation of 17 beta-HSD activity for the
      interconversion E1<-->E2 in hormone-dependent and -independent cells is related
      to the hormonal status of the cells.

PMID- 7647332
TI  - Inhibitory effects of medroxyprogesterone acetate (MPA) and the pure antiestrogen
      EM-219 on estrone (E1)-stimulated growth of dimethylbenz(a)anthracene (DMBA)
      induced mammary carcinoma in the rat.
AB  - Estrogens are well known to play a predominant role in promoting the growth of
      DMBA-induced mammary tumors in the rat. Estrone (E1), a steroid having weak
      estrogenic activity, is one of most important estrogens in post-menopausal women,
      where it is converted into the potent estrogen estradiol (E2) by 17 beta
      hydroxysteroid dehydrogenase (17 beta-HSD) in many peripheral tissues, including
      the mammary gland. In this report, we have studied the effect of a new
      antiestrogen (EM-219) (N-butyl, N-methyl-11-(3', 17'beta-dihydroxy-17'alpha
      ethinyl-estra-1'3'5'(10'), 14'-tetraen-7'alpha-yl) undecanamide) on E1-stimulated
      growth of DMBA-induced mammary tumors and compared its effect with that of
      medroxyprogesterone acetate (MPA) alone or in combination. After 18 days,
      ovariectomy (OVX) reduced total tumor area to 29.6 +/- 7.1% of the original size,
      while E1 (1.0 microgram, twice daily) caused a 139 +/- 21% increase in tumor size
      in OVX animals. MPA (1.5 mg, twice daily) partially reversed the stimulatory
      effect of E1 to 66.0 +/- 9.0%, while the antiestrogen EM-219 (40 micrograms,
      twice daily) decreased tumor size to 70.0 +/- 10%. Combination of these two
      compounds led to a further inhibition of tumor size to 30.7 +/- 7.4% of the value
      found in OVX animals treated with E1. Tumor E2 levels decreased from 1688 +/- 155
      pmoles/kg tissue in OVX animals receiving E1 to 709 +/- 92, 1347 +/- 98, and 184
      +/- 11 pmoles/kg tissue in MPA-, EM-219-, and MPA+EM-219-treated OVX-E1 animals,
      respectively. Treatment of OVX animals with E1 increased by 69% the reductive
      activity of 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) while MPA
      abolished completely this effect of E1. In the oxidative direction, treatment
      with E1, E1 + MPA, or E1 + EM-219 had minimal or no significant effect on the
      activity of 17 beta-HSD (vs OVX), while the combined treatment with MPA+EM-219
      induced a 2-fold increase in 17 beta-HSD activity, thus leading to an increased
      conversion of E2 into E1. The present data show that combination of the pure
      antiestrogen EM-219 with MPA exerts a greater reduction in DMBA-induced mammary
      tumor growth and intratumoral E2 levels stimulated by E1 than either compound
      used alone. This interactive effect of the antiestrogen and MPA could at least
      partially be related to the increased inactivation of E2 into E1.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7647333
TI  - Serum lipids and apolipoproteins in women with breast masses.
AB  - BACKGROUND: Human mammary tissue metabolizes lipids from plasma, a process
      affected by female gonadal hormones. Both benign and malignant proliferation of
      breast tissue in women have been associated with changes in plasma lipid and
      lipoprotein levels. METHODS: One hundred consecutive women with breast masses (50
      malignant, 50 benign) had diagnostic biopsies followed by axillary node
      dissection in those with cancer. Fasting serum samples were taken just prior to
      biopsy and analyzed for lipid fatty acid and lipoprotein levels. Malignant breast
      tissue was analyzed for hormone receptor binding. RESULTS: Low-density
      lipoprotein (LDL) components (total cholesterol, LDL-cholesterol, apolipoprotein
      B) were increased, but not significantly, in cancer patients compared to those
      with benign masses. Decreased levels of LDL-associated components were found in
      women with cancer recurrence by 3 years. Three apolipoproteins of high-density
      lipoprotein (apolipoprotein A-I, apolipoprotein A-II, apolipoprotein D) were more
      affected by the presence of breast masses than the lipids were. Fibrocystic
      disease, type of hormone binding, and recurrence within 3 years were
      significantly related to apolipoprotein changes, especially apolipoprotein D
      levels with hormone receptor binding and the apolipoprotein A-I/apolipoprotein B
      ratio with breast cancer recurrence. CONCLUSIONS: Prior to diagnostic biopsy,
      serum lipid and apolipoprotein components of low-density lipoproteins were
      increased in women with fibrocystic disease and early stage cancer but decreased
      in women with early recurrence. However, apolipoprotein A-I, apolipoprotein A-II,
      and apolipoprotein D, of the high-density lipoproteins, were more affected than
      serum lipids. The ratio of apolipoprotein A-I to apolipoprotein B serum levels at
      time of biopsy was the best predictor of cancer recurrence.

PMID- 7647334
TI  - Familial breast cancer and genes involved in breast carcinogenesis.
AB  - Breast cancer has often been reported to run in families, and the most important
      risk factor for the disease is a family history of breast cancer. Numerous
      pedigrees and segregation analyses have suggested an autosomal dominant
      transmitted susceptibility to breast cancer. Familial breast cancer occurs alone
      or associated with other cancers in clinically distinguishable syndromes. Such
      cases may be characterized by early onset, bilateral disease, prolonged survival,
      and anticipation, mainly seen as a higher penetrance or earlier onset in
      subsequent generations. Studies of patients and tumors from these families as
      well as sporadic cases have led to localization and/or identification of a number
      of genes implicated in breast carcinogenesis of familial and sporadic breast
      cancer.

PMID- 7647335
TI  - Second-line chemotherapy with long-term low-dose oral etoposide in patients with
      advanced breast cancer.
AB  - In a phase II study, 27 patients with metastatic breast cancer were treated with
      oral etoposide as second-line chemotherapy at a dose of 50 mg/m2/day for 21 days,
      which courses were repeated every 4 weeks. Twenty-one patients were evaluable for
      response, and twenty-five for toxicity. In two (10%) patients a partial response
      was observed with a duration of 60 and 122 weeks respectively, and seven patients
      (33%) showed stable disease. Gastrointestinal toxicity was usually mild, though
      relatively frequent. Anemia grade II and III was observed in 20% of all courses
      (< 10% of all measurements), and leukopenia grade III and IV was observed in 22%
      of all courses (< 10% of all measurements). There was one toxic death. Reviewing
      the literature we calculated a response rate of intravenous etoposide treatment
      of 8% in 276 patients with metastatic breast cancer from 7 studies (response
      rates ranging between 0-14%), while (chronic) oral treatment caused a response
      rate of 19% in 145 patients from 8 different studies (response rates ranging
      between 0-35%).

PMID- 7647337
TI  - Difference in thymidylate synthetase activity in involved nodes compared with
      primary tumor in breast cancer patients.
AB  - Thymidylate synthetase (TS) is a key enzyme as a methyl donor in the methylation
      reaction from dUMP to dTMP. TS activity was assessed in various tissue of mammary
      disorders. The descending order of TS activity was as follows: cancer-positive
      nodes, primary cancers, cancer-negative nodes, benign lesions, and normal
      parenchyma. Significant differences in TS activity were found between the
      positive nodes and each of the other tissues (p < 0.01). In node-positive cases,
      a significant correlation in TS activity was found between the primary cancers
      and positive nodes (r = 0.616, p = 0.033). There was no correlation between the
      nodal status and the TS activity in primary cancers. In 11 of 12 cases, the TS
      activity of positive nodes was higher than the 'calculated' TS activity of the
      primary cancer, which was defined as the TS activity per unit weight of cancer
      cells. A significant correlation was found between the calculated TS activity and
      the mitotic frequency in primary cancers (r = 0.697, p = 0.0001). On the other
      hand, a significant correlation could not be found between the TS activity and
      the mitotic frequency in positive nodes (r = 0.364, p = 0.244).

PMID- 7647336
TI  - MCF-7 breast cancer cells overexpressing transfected c-erbB-2 have an in vitro
      growth advantage in estrogen-depleted conditions and reduced estrogen-dependence
      and tamoxifen-sensitivity in vivo.
AB  - A c-erbB-2 expression vector was transfected into the estrogen receptor positive
      (ER+) MCF-7 human breast cancer cell line to determine if overexpression of this
      transmembrane tyrosine kinase could increase the malignant phenotype of this cell
      line. Loss of transfected c-erbB-2 expression was observed when cells were
      carried in medium containing estrogen. Homogeneous populations stably
      overexpressing levels of the 185 kDa c-erbB-2 observed in the SKBR-3 a breast
      cancer cell line which overexpresses c-erbB-2 as a result of gene amplification
      could be obtained by continually maintaining the transfected cell lines in
      estrogen-free conditions. Levels of constitutively activated c-erbB-2 varied
      among clonal isolates. Whereas some overexpressing lines did acquire the ability
      to form transient tumor nodules in ovariectomized nude mice without estrogen
      supplementation, as well as in mice that received the antiestrogen tamoxifen, one
      cell line that exhibited the highest levels of constitutively activated c-erbB-2
      was able to form static tumors of a larger size under both conditions. This same
      cell line formed progressively growing tumors in estrogen-supplemented mice that
      were much larger than observed in mice injected with control cell lines, and also
      showed reduced sensitivity to antiestrogens in vitro, but it continued to have a
      low metastatic phenotype. These results suggest that signal transduction mediated
      by the c-erbB-2 tyrosine kinase can partially overcome the estrogen dependence of
      ER+breast cancer cells for growth and that c-erbB-2 overexpression confers a
      selective advantage to such cells in the absence of estrogen.

PMID- 7647338
TI  - Oncologic and cosmetic outcome in patients with breast cancer treated with wide
      excision, transposition of adipose tissue with latissimus dorsi muscle, and
      axillary dissection followed by radiotherapy.
AB  - We evaluated the oncologic and cosmetic outcome in patients with breast cancer
      treated with wide excision, transposition of adipose tissue with latissimus dorsi
      muscle (LDM), and axillary dissection followed by radiotherapy. In this study, a
      wide excision of breast tissue was performed to obtain tumor-free margins. The
      subsequent breast deformity was not corrected in six patients in the early phase
      of the study (Group 1), and in 16 patients in the late phase (Group 2) in which
      the breast deformity was not remarkable at the time of operation. Breast
      deformity was corrected by transposing adipose tissue with LDM on a vascular
      pedicle in the remaining 51 patients (Group 3). Five year survival was 100%. Two
      patients developed distant metastases. None were found to have local recurrence.
      Fifty percent of the Group 1 patients, 69% of the Group 2 patients, and 67% of
      the Group 3 patients had an excellent or good cosmetic result. However, when the
      cosmetic results were evaluated in patients who underwent transposition and had
      small breasts, the results were excellent or good in 76%, compared to 38% in the
      patients who had reconstructions who had large breasts. The difference was
      statistically significant (p = 0.0309). Therefore, it was confirmed that wide
      excision and axillary dissection followed by breast radiation could provide
      adequate local control, but frequently resulted in breast deformity. However,
      transposition of adipose tissue may be useful to correct the breast deformity,
      especially in women with small breasts.

PMID- 7647339
TI  - Effect of medroxyprogesterone acetate (MPA) and serum factors on cell
      proliferation in primary cultures of an MPA-induced mammary adenocarcinoma.
AB  - The effect of progesterone (Pg), medroxyprogesterone acetate (MPA), estradiol
      (E2), dihydrotestosterone (DHT) and dexamethasone (DEXA) was studied on the in
      vitro growth rate of a progestin-dependent (PD), estrogen-sensitive mammary tumor
      line originated in an MPA-treated BALB/c mouse (C4-HD), and on its estrogen
      resistant variant (C4-HDR). The specificity of hormone action was further
      investigated using the anti-hormones RU-486 and hydroxyflutamide (FLU). Cell
      growth was evaluated in epithelial and fibroblast-enriched cultures using 3H
      thymidine and/or autoradiography and immunocytochemistry. The results indicate
      that cell growth is directly stimulated by MPA and Pg at concentrations ranging
      from 10(-11) to 10(-7) M. RU486 prevented MPA-induced stimulation in
      concentrations 10 to 100 fold lower than those of MPA. When used alone, it
      inhibited cell proliferation only in concentrations higher than 10(-11) M. At nM
      concentrations, neither DEXA nor DHT stimulated 3H-thymidine uptake except DEXA
      at 100 nM. MPA-induced stimulation was not reverted by micromolar concentrations
      of FLU. As for E2 (10(-7)-10(-9) M) it prevented MPA stimulation only in cultures
      of estrogen-sensitive tumors. Progesterone receptors (PR) (475 +/- 115
      fmoles/10(5) cells, n = 5) and estrogen receptors (ER) (ND-115 fmoles/10(5)
      cells, n = 5) were detected only in epithelial-enriched cultures. Serum from 7
      day-MPA-treated mice induced a significant increase of 3H-thymidine uptake; an
      increase was also obtained with serum from untreated ovariectomized animals to
      which 1 nM-100 nM concentrations of MPA had been added. The stimulatory effect of
      the exogenous MPA was much lower than that of the serum obtained from MPA-treated
      animals. It is concluded that MPA stimulates cell growth of primary cultures of
      MPA-induced PD tumors via PR. The results provide support for a direct effect of
      MPA which may be mediated or potentiated by serum factors.

PMID- 7647340
TI  - Chlorpheniramine inhibits the synthesis of ornithine decarboxylase and the
      proliferation of human breast cancer cell lines.
AB  - Proliferation of both mouse and human breast cancer cells was inhibited by
      chlorpheniramine (CPA) in a dose-response manner. At the beginning of the
      exponential phase of growth (two days after seeding), 250 microM CPA was able to
      reduce cell proliferation by 75% (in Ehrlich cell cultures) and 30% (in MCF-7
      cultures). The antiproliferative effect of CPA was also tested on a poorly
      differentiated and hormone-insensitive human breast cancer cell line (MDA-MB231)
      and on a highly proliferative human colon cancer cell line (clone 3). CPA was
      cytotoxic for MDA-MB231 cells at concentrations higher than 50 microM, and it was
      also cytotoxic for the colon cancer cell clone 3 at 250 microM CPA. Nevertheless,
      colon cancer cells were slightly stimulated at CPA concentrations less than 100
      microM. CPA reduced (by 50-70%) the ornithine decarboxylase induction occurring
      early after culture seeding of experimental mammary tumors (Ehrlich carcinoma
      cells) and human breast cancer cells (MCF-7). The presented data suggest that in
      addition to ODC inhibition, CPA presents other still unknown cytotoxic effects.

PMID- 7647341
TI  - Prognostic significance of laminin production in relation with its receptor
      expression in human breast carcinomas.
AB  - Laminin is a basement membrane glycoprotein whose expression has been widely
      related to cancer progression. Laminin production by primary breast carcinomas
      was investigated using immunohistochemistry on archival specimens from a
      retrospective series with long term follow-up. Laminin production was found to be
      independent of the clinical and pathological variables analyzed, whereas a
      statistically significant direct association with the expression of the laminin
      receptor and a negative association with the differentiation-related antigen Ca
      MBr8 were observed. Survival analysis indicated that laminin positivity by itself
      has no prognostic significance. However, when analyzed together with the laminin
      receptor expression, laminin was associated with a good prognosis in receptor
      negative tumors and with the worst prognosis in receptor-positive tumors.

PMID- 7647342
TI  - ErbB-2 oncoprotein overexpression in breast carcinoma: inverse correlation with
      biochemically- and immunohistochemically-determined hormone receptors.
AB  - The relationship between erbB-2 oncoprotein overexpression and hormone receptors
      in breast cancer is controversial. Of 320 infiltrating carcinomas, 75 (23%)
      showed membranous positivity for erbB-2 protein using CB-11 antibody, with 31
      (9.7%) strongly positive. Estrogen and progesterone receptors, determined by both
      biochemical and immunohistochemical assays, were negative more often in strongly
      erbB-2 positive tumors, or were positive at lower amounts, than in 56 tumors
      devoid of CB-11 staining. Strong erbB-2 positivity also correlated with lower
      patient age, higher histopathologic tumor grade, and higher S phase fraction, but
      not with tumor size, lymph node involvement, or DNA aneuploidy. Thirty-three
      lobular carcinomas showed strong erbB-2 positivity as frequently as the overall
      group (9.1%). Cytoplasmic CB-11 positivity without membrane positivity, thought
      not to correlate with true erbB-2 positivity, was observed in 189 (59%) tumors
      with a slight (1-2 +) reaction in 124 (39%) tumors and a moderate-to-strong (3-4
      +) reaction in 65 (20%) tumors. Moderate-to-strong cytoplasmic positivity
      correlated with higher histopathologic grade and negativity for
      immunohistochemical, but not biochemical, hormone receptors. CB-11 cytoplasmic
      positivity may have biological significance.

PMID- 7647343
TI  - Western blotting and isoform analysis of cathepsin D from normal and malignant
      human breast cell lines.
AB  - Cathepsin D from normal (Hs578Bst) and malignant (MCF7, MDA-MB-231) breast cell
      lines has been characterized with regard to its kinetic properties, activity
      levels, precursor and processed M(r) forms, and isoform composition. Normal cell
      cathepsin D appears to have a more neutral pH optimum (pH 3.5) than the cancer
      cell line (pH 3.0-3.2) and greater activity between pH values of 4.0 to 4.5. The
      two cancer cell lines have approximately 1.5 to 2.0-fold increased total acid
      protease activity and 2 to 3-fold increased pepstatin-inhibitable protease
      activity (i.e. cathepsin D) when compared to the normal breast cell line. Western
      blotting indicates that a major processed form of cathepsin D for all three cell
      lines occurs at 31 kDa. The cancer cell lines contain significant amounts of
      cathepsin D precursors of 47 and 42 kDa whereas the normal cell line contains
      little if any of these precursors. Isoelectric focusing indicates that the normal
      cell line contains approximately 50% of its total acid protease activity at pIs
      above 4 whereas the cancer cell lines contain 70-80% of their protease activity
      at such pIs. In addition, the cancer cell lines contain two to three major
      isoforms between pIs of 5.5 and 6.3 which were not present in the normal cell
      line. The isoforms from pI values of 5.5 to 7.3 for all three cell lines are 100%
      pepstatin-inhibitable. In addition, Western blot analysis indicates that these
      isoforms contain the processed 31 kDa form of cathepsin D. The combined results
      indicate that the two breast cancer cell lines are similar to biopsied malignant
      breast tissue in exhibiting altered acid protease isoform profiles with increased
      relative amounts of pepstatin-inhibitable and immunoreactive acid protease
      activity (cathepsin D) compared to normal breast tissue or cells.

PMID- 7647344
TI  - Mastopathy of the accessory breast in the bilateral axillary regions occurring
      concurrently with advanced breast cancer.
AB  - We herein report a 41-year-old Japanese woman who demonstrated advanced cancer in
      the left breast occurring concurrently with mastopathy of the accessory breast
      tissue in the bilateral axillary regions, which appeared to be metastatic
      lymphadenopathy. A preoperative examination, including a mammogram, US, and CT,
      did not provide us with a definite diagnosis of the axillary masses: it was
      essential to diagnose the masses preoperatively since a bilateral mastectomy with
      nodal dissection is called for if the right axillary masses are metastatic from a
      cancer in the right breast. An intraoperative cytological examination from the
      bilateral axillary masses revealed adenosis with fibrocystic changes in the
      accessory breast tissue. We therefore performed a modified radical mastectomy
      only on the left side. The patient was thus saved from an unnecessary mastectomy
      of the right breast. Based on our experience, we wish to emphasize that the
      accessory breast tissue should be considered for a differential diagnosis when
      evaluating the axillary masses in order to avoid over-surgery, especially when a
      patient has been diagnosed to have massive breast cancer. An intraoperative
      cytological examination is strongly recommended to reach a final diagnosis in
      such confusing cases.

PMID- 7647346
TI  - Adrenergic systems 100 years after Discovery of Adrenaline. The symposium on the
      occasion of English and Polish contribution to the discovery of adrenaline.
      Cracow, Poland, May 26, 1995. Abstracts.

PMID- 7647345
TI  - The potential for oxytocin (OT) to prevent breast cancer: a hypothesis.
AB  - This hypothesis proposes that carcinogens in the breast are generated by the
      action of superoxide free radicals released when acinal gland distension, under
      the influence of unopposed prolactin, causes microvessel ischaemia. Inadequate
      nipple care in the at-risk years leads to ductal obstruction preventing the
      elimination of carcinogens from the breast. The regular production of oxytocin
      (OT) from nipple stimulation would cause contraction of the myoepithelial cells,
      relieving acinal gland distension and aiding the active elimination of
      carcinogenic fluid from the breast. Mechanical breast pump stimulation causes an
      increase in plasma OT levels in the luteal but not in the follicular phase of the
      menstrual cycle. OT production upon nipple stimulation in the luteal phase of
      premenopausal, non-lactating women may be protective against the high rates of
      mitotic breast cell division noted at this time via the potential to block the
      effect of oestrogen. The epidemiology of breast cancer suggests that lengthy
      lactation time is beneficial. Sexual activity in nulliparous women also protects
      and OT levels have been shown to rise with orgasm in women and in men. OT systems
      in the brain are intricately linked to oestrogen and progesterone levels, and it
      is possible that these hormones may modify the OT secretory response both
      centrally and through an effect on the sensitivity of the breast. OT production
      with nipple care and in sex and lactation, and the reduction in cycling ovarian
      hormones that occurs with pregnancy, may all be important preventative factors in
      the development of breast cancer both pre- and post-menopausally.

PMID- 7647347
TI  - [Family intervention for schizophrenia based on expressed emotion (EE) research:
      a review of the technique and evaluation].
AB  - The present study reviews eight series of trials on psycho-social family
      intervention for schizophrenia based on Expressed Emotion (EE). All studies used
      randomized controlled trials (RCT) except one which was non-randomized controlled
      trial. The relapse risk ratios (intervention/control) for 9-12 months after
      discharge were 0 to .73 and for 24 months were .20 to .57. Taking into account
      the shortcomings of the studies, the authors conclude that psycho-social family
      intervention based on EE is effective in preventing schizophrenic relapse, and
      discuss four important issues: 1) For effective family intervention, methods for
      Japanese patients should be established from a trans-cultural view point; 2) The
      interaction of two or more therapeutic measures should be evaluated
      quantitatively; 3) The mechanisms of schizophrenic relapse prevention through
      family psycho-social intervention should be explored. A psycho-physiological
      study including skin conductance measurement is promising; 4) The authors point
      out the ethical aspect of family intervention, and discuss the importance of
      informed consent and the need to place emphasis on family's needs.

PMID- 7647348
TI  - [Efficacy of smoking cessation instruction for general smokers at an annual
      physical examination].
AB  - A randomized controlled trial was conducted to evaluate the efficacy of smoking
      cessation instruction given to general smokers at an annual physical examination.
      Four hundred and twenty-six male and 42 female clients were randomly assigned to
      an intervention group (I), and 413 males and 76 females were assigned to a
      control (C) group. The I group was given an approximately 2-minute smoking
      cessation instruction by physicians, answered a quiz concerning tobacco, chose
      their own behavioral goals and were handed a leaflet on how to quit smoking.
      Subjects in both groups responded to a self-administered questionnaire and a 6
      month and 12-month follow-up was performed by post card or telephone. The I group
      received an encouragement card one month after instruction and abstainers of the
      I group were awarded a telephone card at the 6-month follow-up. The results were
      as follows: 1) The male I group exhibited 7.3% (6 months), 10.1% (12 months)
      abstinence rates and the male C group 4.4% (6 months), 5.3% (12 months),
      respectively. The difference in 12-month abstinence rates was statistically
      significant. 2) The female I group exhibited abstinence rates of 16.7% (6
      months), 23.8% (12 months) and the female C group 14.5% (6 months), 17.1% (12
      months), respectively. 3) A multivariate analysis of smoking cessation showed
      that lower nicotine dependency, strong determination for smoking cessation, and
      being female were significant factors for abstinence at the 6-month follow-up. At
      12 months, the smoking cessation instruction also became a significant factor.
      These data suggest that a simple smoking cessation instruction at an annual
      physical examination was effective for general smokers.

PMID- 7647349
TI  - [AIDS control in industry in Okinawa Prefecture, Japan].
AB  - To see how industry is responding to AIDS, an anonymous questionnaire survey was
      conducted on member companies (n = 407) of the chamber of commerce with 50 or
      more employees in three large cities in Okinawa, during February to March, 1994.
      Responses were obtained from 221. The questionnaire looked at type of industry,
      number of employees, number of business trips to foreign countries, specialists
      for health management, AIDS control, attitudes and actions taken toward infected
      persons and AIDS patients, etc. The main results were as follows; In 73 companies
      foreign business trips had been made. The rate of appointment of specialists in
      health management was below 50%. In 80% of the companies, AIDS control was not in
      place. About 1/2 of the companies responded that there was a need to grapple with
      AIDS control while 40% of the companies were undecided. The majority of the
      companies felt that there was no chance of their employees having HIV infection
      within five or six years. Many companies had no regulations for dealing with
      employees who are infected with HIV. From the survey, three points were made
      clear: 1. Industry does not have an adequate plan to deal with AIDS. 2. There is
      no awareness of a crisis. 3. There is insufficient dissemination of information
      regarding AIDS. HIV/AIDS is predicted to increase in industries in our country
      and management will be hard-pressed to deal with the intricate problems that
      arise. HIV/AIDS is not exclusively an individual problem, but should be the
      concern of industries and society as well.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7647350
TI  - [Exposure to blood during midwifery procedures--blood contact events to midwives
      occurred in a delivery room].
AB  - Midwives are often exposed to blood during delivery procedures. A study aimed at
      clarifying actual status of blood contact during midwifery procedures was
      performed. Observations in a delivery room were conducted to record blood contact
      events experienced by midwives from the time of episiotomy until 2 hour after
      expulsion of the placenta. All gloves used by midwives were collected and tested
      for holes. Blood contact was defined as any contact with blood of a parturition
      woman as recognized visually by an observer. During a one-month study period data
      was obtained from a total of 19 midwives (12 midwives and 7 student midwives) who
      assisted in 8 deliveries. All of the midwives wore gowns with long sleeves,
      gloves and caps but did not use eye protection or masks. None of the parturient
      women had Hepatitis B, Hepatitis C or acquired immunodeficiency syndrome.
      Deliveries caused widespread blood exposure to the midwives throughout the
      complete course. Protection from most of this exposure was provided by the gowns
      and gloves. However, direct blood contacts occurred to the fingers, hands or
      forearms in several midwives. These events were caused by partly because the
      midwives unintentionally performed procedures without gloves and partly because
      blood penetrated the gown and soaked to the skin. Direct blood contacts to the
      foot in two midwives and to the mouth in one also occurred. The overall
      perforation rate for gloves examined was 4 out of 154 (2.6%). Two gloves were
      broken during washing sharp instruments contaminated with blood, one was torn
      when wearing, and the remaining one appeared to have had a hole prior to
      use.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7647351
TI  - [Acute encephalitis and bacterial meningitis in children in Aichi Prefecture
      (1984-1993)].
AB  - A survey was performed of acute encephalitis and bacterial meningitis in infancy
      and childhood from 1984 to 1993 using a questionnaire directed to departments of
      pediatrics in large hospitals in Aichi prefecture. The case records for 391
      patients with acute encephalitis including related diseases and 328 patients with
      bacterial meningitis were obtained from 63 hospitals. Of 391 patients with acute
      encephalitis, 224 were male and 167 were female. Of 328 patients with bacterial
      meningitis, 200 were male and 128 were female. Sex ratio were 1.3, 1.6
      respectively. Of the patients, 52.4% of encephalitis and 84.8% of meningitis were
      under 4 years of age and 0 year olds made up 53.7% of the latter. The causes of
      these diseases were confirmed in 38.7% and 82.9% of the encephalitis and
      meningitis patients, respectively, etiologically. In encephalitis, rubella virus
      was the most frequent with 29 cases, followed by measles virus (27 cases), herpes
      simplex virus (24) and varicella-zostervirus (19). In meningitis H. influenzae
      (95 cases), S. pneumoniae (56), Group B streptococcus (41) and E. coli (27) were
      frequently diagnosed. These diseases showed respective patterns of age
      distribution and clinical course, and moreover, the increases in their onset were
      clearly related to the prevalence of causal infections. Therefore, the results of
      this study should be utilized in the development of administrative measures for
      prevention of these diseases.

PMID- 7647352
TI  - [The state and function of day hospital belong to a community medical office].

PMID- 7647353
TI  - [Importance of smoking prevention among minors].

PMID- 7647354
TI  - [Development of research on self-rated health in the United States].
AB  - The development of research on self-rated health in the United States was
      reviewed to elucidate the background of the research. The earliest studies
      utilized medical and objective health data to assess self-rated health. A lack of
      convenient and exact health measurements in the gerontological research field
      motivated the development of these early studies. These studies indicated that
      self-rated health could not serve as a substitute for physicians' ratings. On the
      other hand, studies of the relationship between psychosocial indices and self
      rated health demonstrated that self-rated health was valid as a single measure of
      overall health, being related to physical, mental and social aspects of well
      being. Recent epidemiological investigations have shown that self-rated health is
      a significant predictor of mortality and changes in activities of daily living.
      Most of these research studies on self-rated health utilized elderly populations
      for subjects.

PMID- 7647355
TI  - [Mass-screenings for osteoporosis using computed X-ray densitometry (CXD): in a
      mobile unit].
AB  - The early diagnosis and treatment of osteoporosis is considered to be important
      for the prevention of fractures which often cause elderly to become bed-ridden.
      Computed X-ray densitometry (CXD), a method to measure bone mineral content in
      the metacarpus II utilizing a simple X-ray image, has been used for mass
      screening of osteoporosis, because of its utility and reliability. However, due
      to its requiring adequate X-ray equipment, this method is often unsuitable for
      use in small facilities in a remote mountain areas. The use of CXD for
      osteoporosis screening, was attempted in a mobile unit for tuberculosis
      screening, by our public health center. The results showed that it is possible to
      use CXD in combination with a mobile unit, correcting the obtained values
      according to the radiographic conditions. With this set-up, CXD was used for mass
      screening of osteoporosis in a total of 1150 subjects living in mountainous areas
      of Yoshino-gun, Nara prefecture, and CXD was found to be convenient and effective
      for mass-screening. The use of CXD in a mobile chest X-ray unit can be expected
      to be useful for mass-screening of osteoporosis especially in remote mountainous
      areas having inadequate X-ray equipment.

PMID- 7647357
TI  - [A survey of utilization of urinary alarm systems in nursing homes].
AB  - A questionnaire survey was performed on 63 nursing homes and 1006 care workers in
      the nursing home, in order to elucidate the actual state of utilization of
      urinary alarm systems (systems). About 3% of the nursing homes in all of Japan
      are utilizing the system with 12.5% of all institutionalized elderly having a
      diaper sensor of those nursing homes with the system, 86% use the system
      continually. In 51% of the nursing homes, care workers change diapers immediately
      after sensor alarm is triggered. The reasons for not being able to change the
      diaper immediately were either care workers had other pressing work, or
      simultaneous or overlapping sensor alarm calls occurred. The usefulness of the
      system was recognized for "prevention of decubitus" (66%), "prevention of contact
      dermatitis from diapers" (82%), "decrease of ammonia smell" (27%), and
      "discontinuation of diaper" (26%). As for problems associated with the system or
      factors that increase work load, responses included "sensor does not respond
      sometimes" (67%), "increased diaper changes" (53%), "increased nurse calls due to
      urinary urgency" (41%), and "disconnection of the sensor by the patient" (34%).
      The percentage of care workers who reported an increase in work load was 73%,
      especially where the ratio of care workers number/institutionalized elderly was
      low.

PMID- 7647356
TI  - [Appropriateness and limitations of bone mineral measurements by DXA (dual energy
      x-ray absorptiometry) in the elderly--comparison with x-ray findings].
AB  - A group of 674 (266 males and 410 females) elderly living in a rural community of
      Nangai Village, Akita Prefecture, were subjects of bone mineral measurements in
      the lumbar spine and three areas of proximal femur (femoral neck; FN, trochanter;
      TR and Ward's triangle; WD). Measurement was by dual energy x-ray absorptiometry
      (DXA) set in a mobile van during mass health examination. The purpose of this
      study was to verify the appropriateness and imitations in the bone mineral
      measurements by DXA in elderly who have other aging related abnormal
      calcifications such as osteophytosis in the lumbar spine and calcification of the
      abdominal aorta, all of which may have an influence on the 'true' value of bone
      mineral density (BMD) particularly in the lumbar region. The results were as
      follows: 1) Subjects who were not capable of being measured by DXA tended to be
      older and reported experiencing pain and who scored low in TMIG index of
      competence compared to measurable subjects. 2) BMD of 2nd-4th lumbar spine with
      antero-posterior projection (AP) did not show simple age-declines that are seen
      in younger generations. In contrast, BMDs of proximal femur show linear aging
      declines. 3) Analysis of the association between BMDs and osteophytosis by
      spondylosis deformans in the lumbar spine and calcification of the abdominal
      aorta in front of the lumbar spine showed that AP-BMD had a strong correlation
      with the grade of both spinal osteophytosis and aortic calcification. On the
      other hand, BMDs of proximal femur showed no significant associations with these
      abnormal calcifications. 4) In this context, in order to evaluate the 'true' BMD
      in the elderly, BMDs in the proximal femur are a more appropriate indicator than
      AP-BMD which may be easily contaminated by other aging-related calcification in
      and around the lumbar region.

PMID- 7647358
TI  - [Application of volunteer to guidance for "no smoking"--activity at Aichi Anti
      Lung Cancer Association Tobacco Countermeasure Center].

PMID- 7647359
TI  - [The state of environmental problems in Vietnam].
AB  - Following the introduction of a market economy, Vietnam has been faced with a
      variety of environmental problems. The following eight problems deserve special
      attention; 1) deforestation, 2) decrease of agricultural land resources, 3)
      irrational use of water resources, 4) over exploitation of fishery resources, 5)
      irrational use of mineral resources, 6) loss of genetic resources, 7)
      environmental pollution, 8) environmental damage due to war. In order to solve
      these problems, the Vietnamese government established an integrated strategy, the
      "National Environmental Protection Research Program: NEPRP". However, because of
      shortages in human resources, adequate technology, and financial resources, it is
      very difficult for the Vietnamese government to fully implement this program. As
      the realization of a sound economic development in the Indochina area is very
      important from the international political point of view, strong expectations
      exist that developed countries, including Japan, will actively contribute to the
      solution of these environmental problems in Vietnam.

PMID- 7647360
TI  - Biosynthesis of melanin from dopamine. An investigation of early oligomerization
      products.
AB  - Matrix-assisted laser desorption/ionization (MALDI) and fast-atom bombardment
      (FAB) mass spectrometry experiments were applied to the study of the early stages
      of the oligomerization reaction of dopamine with mushroom tyrosinase.
      Ultrafiltration was employed to remove the enzyme at various reaction times, to
      prevent possible attachment of the protein to the highly reactive intermediates.
      Two sets of five samples each, obtained at different reaction times, in one case
      immediately lyophilized and in the other left to react under an oxygen stream for
      24 h before lyophilization, were compared. FAB showed the presence of various
      species and of these, that at m/z 305 increased in abundance with reaction time
      in immediately lyophilized set of samples only. Accurate mass measurements and
      tandem mass spectrometric experiments indicated the structure of a dopamine
      protonated dimer for this ion. MALDI measurements showed that all samples were
      composed of clusters of oligomers differing in degree of oligomerization.
      Oligomerization increases with reaction time, resulting in the formation of
      species at 2643-2911 Da. These clusters in turn were formed of species with a
      different degree of oxidation, detected in both sets of samples.

PMID- 7647361
TI  - Sensitive detection and structural characterization of trimethyl(p-aminophenyl)
      ammonium-derivatized oligosaccharides by electrospray ionization-mass
      spectrometry and tandem mass spectrometry.
AB  - Mass spectrometric methodologies which use electrospray ionization (ESI) for
      oligosaccharide structural determination and which are linked to classical
      procedures, such as reductive amination, have been established. Several
      derivatives of a model oligosaccharide were prepared and their ionization
      efficiencies in electrospray ionization (ESI) and fast-atom bombardment (FAB)
      mass spectrometry were investigated. The trimethyl-(p-aminophenyl)ammonium
      (TMAPA) derivatives showed extremely high sensitivity in positive-ion ESI-MS and
      gave Y- and Z-series sequence ions by ESI tandem mass spectromety (MS/MS). This
      study suggests that TMAPA-derivatized oligosaccharides used in ESI-MS and ESI
      MS/MS would be effective for structural characterization of oligosaccharides that
      are available only in limited quantities.

PMID- 7647362
TI  - Bio-affinity characterization mass spectrometry.
AB  - A new approach, bio-affinity characterization mass spectrometry (BACMS), aimed at
      providing a more rapid, sensitive and potentially more flexible alternative to
      techniques presently employed for the characterization of noncovalent
      interactions in mixtures, such as would be encountered in combinatorial
      chemistry, in presented. BACMS avoids some of the difficulties and potential
      artifacts associated with affinity chromatography since the noncovalent
      associations occur in solution; thus, BACMS avoids the requirement of solid
      support media and the development of non-interfering linker species. This paper
      describes the conceptual basis for the methodology and its potential use in
      applications which include the screening of high affinity ligands in support of
      new drug development. BACMS exploits new Fourier-transform ion cyclotron
      resonance (FTICR) mass spectrometry technologies which, when coupled to
      electrospray ionization (ESI), allow the investigation of specific noncovalent
      complexes formed in solution. BACMS utilizes the well-known attributes of FTICR,
      such as the high resolution mass analysis and (MS)n (n > or = 2) capabilities;
      however, it is even more directly a result of recently developed techniques
      involving quadrupolar excitation, such as selected-ion accumulation. These tools
      are demonstrated and the results illustrate the extraordinary sensitivity
      achievable (solution concentration of 1 x 10-9 M without the use of separations
      prior to ESI). Thus, the new capabilities demonstrated here, in conjunction with
      ESI, will be useful for the investigation of very low relative concentration
      noncovalent association directly from solution, and promote a faster alternative
      for combinatorial mixture screening and analysis.

PMID- 7647363
TI  - Determination of multiply labeled serine and glycine isotopomers in human plasma
      by isotope dilution negative-ion chemical ionization mass spectrometry.
AB  - A gas chromatography/negative-ion chemical ionization mass spectrometry method is
      presented to measure the isotopic enrichment of multiple serine and glycine
      isotopomers. The amino acid N-heptafluorobutyryl n-propyl ester derivatives were
      used. The method had good analytical linearity between 10 and 800 microg mL-1 and
      both precision and accuracy were 5% for plasma amino acids. Sensitivity permitted
      analysis of 100 pg amino acid on column. The method was applied to metabolic
      studies of the serine to glycine interconversion in humans. (alpha-15N)serine and
      (1,2-13C2)glycine were given as a single intravenous bolus to six healthy male
      subjects. Plasma concentration of glycine and serine were determined after
      addition of (alpha-15N,1,2,3-13C3) serine and (alpha-15N,1,2-13C2)glycine as
      internal standards to 500 microL of plasma. Since glycine and serine are rapidly
      interconverted by hepatic serine hydroxymethyl transferase, the resultant tracer
      spectrum requires deconvolution of the enrichment of four isotopomers of each
      amino acid. Deconvolution of the ion abundance ratios to yield tracer-to-tracee
      ratios for each isotopomer was done using Brauman's least squares approach.

PMID- 7647364
TI  - Glycosyl compositions and structural characteristics of the potential immuno
      adjuvant active saponins in the Quillaja saponaria Molina extract quil A.
AB  - Fifty saponin components of Quil A, a commercially available extract from the
      bark of the South American tree Quillaja saponaria Molina, were partially
      structurally characterised. The molecular weights were determined by fast-atom
      bombardment mass spectrometry. The glycosyl and elemental composition of all the
      saponins was determined by applying our recently developed method, monomer
      mapping, consisting of a computer program and accurate mass measurements. Support
      for the presumed identity of the aglycone, i.e. quillaic acid, was found in the
      accurate mass determination, 1H NMR measurement and chemical reactions. The
      saponin composition of Quil A was shown to consist of pairs. Within the 3-O bound
      glycosyl moiety of a pair there was a structural difference: a pentose and
      rhamnose were interchanged. Structural differences between different pairs were
      located in the 28-O bound glycosyl moiety. A structural element, unknown to date
      and of which the elemental composition was deduced to be C8H12O5, was found in
      the 28-O bound glycosyl moiety of several saponins.

PMID- 7647365
TI  - Characterization of underivatized tetrapeptides by negative-ion fast-atom
      bombardment mass spectrometry.
AB  - The [M-H]- ions derived from tetrapeptides generally show two different collision
      induced backbone cleavages which allow the determination of the amino acid
      sequence of the peptide. The first of these involves the formation of the
      carboxylate anions of either constituent amino acids or fragment peptides. In the
      second, amino acids or fragment peptides are eliminated as neutrals. There are a
      number of residues which undergo characteristic side-chain fragmentations
      irrespective of their position in the tetrapeptide, e.g. Ser, Thr, Cys, Met, Phe,
      and Tyr. However, there are also some residues which, when situated at the C
      terminal end of the peptide, promote pronounced fragmentation at the C-terminal
      position which occurs to the exclusion of the normal backbone cleavages. We
      conclude that the data obtained from these negative-ion cleavages are
      analytically useful, and complement those provided by the cognate positive-ion
      technique.

PMID- 7647366
TI  - 252Cf-plasma desorption mass spectrometry analysis of lipids A obtained by an
      elimination reaction under mild conditions.
AB  - Lipids A are the hydrophobic domains of bacterial endotoxic lipopolysaccharides.
      Since they are responsible for most of the biological activities (both pathogenic
      and beneficial) of endotoxins, the characterization of their structure is crucial
      to the understanding of their mode of action. However, the inadequacy of existing
      methods for preparing certain lipids A has prompted us to devise a new, mild
      procedure which gives intact products. Use was made of the special features of
      252Cf-plasma desorption mass spectrometry for forming molecular ions from these
      species and giving qualitative and quantitative information from the primary mass
      spectrum.

PMID- 7647367
TI  - Characterization of oligomers in poly(ethylene terephthalate) by matrix-assisted
      laser desorption/ionization mass spectrometry.
AB  - Matrix-assisted laser desorption/ionization mass spectrometry was used for the
      characterization of extracted and synthesized oligo(ethylene terephthalate)s.
      Generally, cyclic oligomers [GT]n could be found in technical yarns and tiles,
      whereas our synthesized model oligomers mainly consisted of linear chains H-[GT]n
      G. In addition, some other distributions could be identified as H-[GH]n-OH and H
      [GGT]1-[GT]n-7/-G linear oligomers and H-[GGT]1-[GT]n-1 cyclic oligomers, where G
      is an ethylene glycol unit, GG is a diethylene glycol unit, caused by impurities
      of ethylene glycol, and T is a terephthalic acid unit. NMR and IR investigations
      were carried out to verify these results.

PMID- 7647368
TI  - Structural characterization of a new class of penem beta-lactam antibiotics by
      triple quadrupole tandem mass spectrometry.
AB  - A series of new penem beta-lactam antibiotics, having at position 2 of the
      thiazoline ring an amido-substituted amino acid moiety spaced by a methylene
      group, was analyzed by collisionally activated dissociation (CAD) tandem mass
      spectrometry on a triple-quadrupole mass spectrometer, after ionization by cesium
      ion bombardment. This approach allowed complete structural characterization
      without any matrix interferences. All the compounds investigated underwent beta
      lactam ring cleavage through a typical retro-Diels-Alder reaction, as well as
      cleavage of the 2-side chain at two different points, with charge retention on
      both sides of the molecule. Subsequent fragmentation reactions essentially
      involved combinations of the above processes.

PMID- 7647369
TI  - Contribution of mass spectrometry to the structural confirmation of components of
      the antibiotic GE2270 complex.
AB  - The GE2270 complex consists mainly of GE2270 A (MW 1289), a thiazolyl peptide
      antibiotic whose structure originates from the modification of a chain of 14
      amino acids in a process which creates six thiazole rings and one pyridine.
      Together with the main component, a number of structurally related molecules are
      co-produced in small quantities by fermentation. A preparative high-performance
      liquid chromatrography method was developed to isolate GE2270 factors B1, B2, C1,
      C2a, C2b, D1, D2, E and T. Their structures, preliminarily determined by 1H
      nuclear magnetic resonance spectroscopy in comparison with GE2270 A, were
      confirmed by low and high resolution fast-atom bombardment mass spectrometry and
      studies on the intact molecules and on their main hydrolysis products. Their
      molecular weights range from 1246 to 1306 Da. The structural differences between
      the factors lie in the extent of methylation and/or oxidation of thiazole rings
      (D and E) and asparagine, and in the aromatization of the oxazoline ring.

PMID- 7647370
TI  - Differential expression of the chicken Pax-1 and Pax-9 gene: in situ
      hybridization and immunohistochemical analysis.
AB  - We report the cloning, partial sequence analysis, and spatiotemporal expression
      of the chicken Pax-1 (chPax-1) and Pax-9 (chPax-9) gene, two closely related
      members of the paired box-containing (PAX) gene family. The chPax-1 gene encodes
      RNAs of 2.0 and 4.3 kb and a 42 kD protein while the gene products of chPax-9 are
      represented by 1.9 and 3.1 kb transcripts and a 39 kD protein. In situ
      hybridization and immunohistochemical analyses reveal chPax-1 expression in the
      developing pectoral girdle, in cells of the ventral part of sclerotomes, in
      sclerotome cells of the perichordal tube, and, later in development, in
      sclerotome-derived cells of the intervertebral disks. Other chPax-1 expression
      domains detected in the mesenchyme surrounding the atlas and axis and in
      chondrocytes of immature vertebral bodies, so far unreported for mouse Pax-1,
      correlate with as yet unexplained malformations in the mouse Pax-1 mutant
      undulated and Undulated-short tail. Overlapping expression of chPax-1 and chPax-9
      is detected in epithelial cells of the embryonic and adult thymus and in cells of
      the developing intervertebral disks. Unlike chPax-1, however, chPax-9 is not
      expressed in those perichordal sclerotome cells which are thought to give rise to
      vertebral bodies. Furthermore, chPax-9 gene products are detected in
      circumscribed areas of mesenchyme in the metatarsus and in entodermal
      derivatives, i.e., in the lining epithelium of the developing pharynx and of the
      embryonic and adult esophagus.

PMID- 7647371
TI  - Cell cycle of globose basal cells in rat olfactory epithelium.
AB  - The olfactory epithelium of adult mammals has the unique property of generating
      olfactory sensory neurons throughout life. Cells of the basal compartment, which
      include horizontal and globose basal cells, are responsible for the ongoing
      process of neurogenesis in this system. We report here that the globose basal
      cells in olfactory epithelium of rats, as in mice, are the predominant type of
      proliferating cell, and account for 97.6% of the actively dividing cells in the
      basal compartment of the normal epithelium. Globose basal cells have not been
      fully characterized in terms of their proliferative properties, and the dynamic
      aspects of neurogenesis are not well understood. As a consequence, it is
      uncertain whether cell kinetic properties are under any regulation that could
      affect the rate of neurogenesis. To address this gap in our knowledge, we have
      determined the duration of both the synthesis phase (S-phase) and the full cell
      cycle of globose basal cells in adult rats. The duration of the S-phase was found
      to be 9 hr in experiments utilizing sequential injections of either IdU followed
      by BrdU or 3H-thy followed by BrdU. The duration of the cell cycle was determined
      by varying the time interval between the injections of 3H-thy and BrdU and
      tracking the set of cells that exit S shortly after the first injection. With
      this paradigm, the interval required for these cells to traverse G2, M, G1, and a
      second S-phase, is equivalent to the duration of one mitotic cycle and equals 17
      hr. These observations serve as the foundation to assess whether the cell cycle
      duration is subject to regulation in response to experimental injury, and whether
      such regulation is partly responsible for changes in the rate of neurogenesis in
      such settings.

PMID- 7647372
TI  - Pattern of muscle fiber type formation in the pig.
AB  - The aim of this study was to analyze the temporal sequence of expression of the
      myosin isoforms in the populations of muscle fibers in the pig and to bring more
      information on the origin of the strikingly different pattern of fiber
      composition and distribution between the deep medial red (oxido-glycolytic) and
      superficial white (glycolytic) portions of semitendinosus (ST) muscle. Muscle
      samples were taken from 49-, 55-, 75-, 90-, 103-, and 113- (birth) day-old
      fetuses, from 6-, 11-, 21-, 35-, 50-, and 80-day-old piglets, and from a 3-year
      old pig. Our results confirm the sequential formation of primary and secondary
      generation fibers. The use of immunohistochemistry and heterologous monoclonal
      antibodies (mAb) directed against specific myosin heavy chain (MHC) isoforms
      revealed a different pattern of gene expression between the two portions of the
      ST muscle for both generations of fibers. By 75 days of gestation (dg), primary
      myotubes from the deep medial portion stained positively for the anti-slow MHC
      mAb and negatively for the adult anti-fast MHC, whereas the opposite was observed
      in the superficial portion. Secondary fibers never expressed slow MHC until late
      gestation. Instead, they expressed an adult fast MHC isoform as soon as they
      formed in the deep medial portion and later on in the superficial portion. From
      late gestation to the first 3 postnatal weeks, slow MHC began to be expressed in
      a subpopulation of secondary fibers. These fibers were in the direct vicinity of
      primary myotubes in the deep medial portion, whereas their location could not be
      established in the superficial portion. The remaining secondary fibers matured to
      type IIA in the direct vicinity of these type I fibers and to type IIB at the
      periphery of the islets. In both portions of the muscle, a subpopulation of
      secondary fibers, the first ones to express slow MHC, also transitorily expressed
      a MHC that was identical or closely related to the alpha-cardiac MHC during the
      early postnatal period. A third generation of small diameter fibers was observed
      shortly after birth and reacted with the anti-fetal MHC mAb; their destiny
      remains to be established.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7647373
TI  - Mechanics of cardiac looping.
AB  - During the early stages of embryonic development, the heart is a smooth-walled,
      muscle-wrapped tube that bends and rotates in a vital, but poorly understood,
      morphogenetic process called looping. Since looping involves biomechanical
      forces, this paper examines two mechanically based hypotheses for the bending
      component of cardiac looping. The first hypothesis is that an initial tension in
      or near the dorsal mesocardium (DM), a longitudinal structure along the outside
      of the ventricle, drives the deformation. To relieve the bending stresses in the
      tube, the myocytes change shape passively, and then they deform actively to
      continue the process to completion of a full loop. In the second hypothesis,
      contraction of circumferentially arranged actin macrofilaments produces
      circumferential compression and longitudinal expansion (due to incompressibility)
      of the myocytes. The DM locally constrains the longitudinal deformation, forcing
      the tube to bend. The feasibility of these hypotheses was evaluated using
      theoretical models and published experimental results. The models, which consist
      of beams composed of two layers representing the DM and the ventricular
      myocardium, show that the hypotheses are consistent with most of the known data,
      but further studies are necessary. In this regard, the models provide a
      conceptual framework for designing experiments to investigate the mechanics of
      looping.

PMID- 7647374
TI  - Developmentally regulated neural protein EAP-300 is expressed by myocardium and
      cardiac neural crest during chick embryogenesis.
AB  - The spatiotemporal distribution of EAP-300 (embryonic avian polypeptide of 300
      kDa) was analyzed in embryonic chick heart using immunohistochemistry and
      confocal microscopy. EAP-300 is a developmentally regulated protein initially
      characterized in neural cells from chick retina. Myocardial cells all along the
      early tubular heart were ubiquitously immunolabeled for EAP-300 by embryonic day
      2 (E2, Stage 13)). At E5 (Stage 24), myocardial EAP-300 expression levels
      remained significant in both atrial and ventricular myocardium. At E6 (Stage 28),
      distinct populations of EAP-300 immunolabeled cells were also observed external
      to the heart, in septal mesenchymal tissue and neural ganglia adjacent to the
      outflow tract; these cell populations were confirmed as neural crest-derived by
      co-localization of EAP-300 and HNK-1. At E13 (Stage 39), myocardial
      immunolabeling for EAP-300 was no longer ubiquitous, but increasingly restricted
      to conduction tissues, including the atrioventricular bundle and subendocardial
      Purkinje cells. This restriction of immunolabeling could be demonstrated
      definitively at E15 (stage 41), by which stage subendocardial and periarterial
      Purkinje fibers were clearly immunoreactive for EAP-300 and several known markers
      of chick conduction tissue, including specific myosin heavy chain isoforms and
      connexin42, a gap junctional protein preferentially expressed by Purkinje fibers.
      Just prior to hatching at E21 (Stage 46), immunolabeling of conduction tissues
      was reduced, although still above that of non-conductile myocardium. This
      spatiotemporal map of cardiac EAP-300 expression indicates that it is
      independently and transiently expressed in early myocardium, cardiac conduction
      tissue, and neural crest derivatives during development.

PMID- 7647375
TI  - Expression of runt in the mouse embryo.
AB  - The Drosophila runt locus controls early events in embryogenesis. A human
      homologue (CBFA2) was originally identified because of its involvement in the
      t(8;21) associated with a subtype of acute myeloid leukaemia. The
      phylogenetically conserved region (runt box) was reported to correspond to a DNA
      binding domain. In order to investigate whether runt also plays a role in
      mammalian development, we have conducted a preliminary survey of its expression
      in the mouse embryo. Expression in embryonic tissues was detected starting from
      day 9.2 post coitum. From day 10.5 post coitum, highest levels are found in the
      neural tube, sensory ganglia, specialised sensory epithelial structures
      (olfactory and gustatory mucosa, follicles of the vibrissae), all chondrogenic
      centres (both of neural crest and of mesodermal origin), and the genital system
      (the gonad, the paramesonephros, and the genital tubercle). Unambiguous
      expression in the haemopoietic system could be established for the thymus. The
      data suggest a pleiotropic role for mammalian runt in embryogenesis.

PMID- 7647376
TI  - Vascularization of the mouse embryo: a study of flk-1, tek, tie, and vascular
      endothelial growth factor expression during development.
AB  - We report the detailed developmental expression profiles of three endothelial
      specific receptor tyrosine kinases (RTKs) flk-1, tek, tie, as well as vascular
      endothelial growth factor (VEGF), the flk-1 ligand. We also examined the
      expression of the other VEGF receptor, flt-1, during placental development. flk
      1, tek, and tie transcripts were detected sequentially at one-half day intervals
      starting at E7.0, suggesting that each of these RTKs play a unique role during
      vascularization of the mouse embryo. All three RTKs were expressed in the
      extraembryonic and embryonic mesoderm in regions that eventually give rise to the
      vasculature. Except for the expression of tek and flk-1 in the mesoderm of the
      amnion, the expression of these RTKs from E8.5 onwards was virtually
      indistinguishable. An abundant amount of flt-1 transcripts was found in the
      spongiotrophoblast cells of the developing placenta from E8.0 onwards. This
      cellular compartment is located between the maternal and labyrinthine layers of
      the placenta, which both express VEGF. VEGF transcripts were detected as early as
      E7.0 in the endoderm juxtaposed to the flk-1 positive mesoderm, and later in
      development VEGF expression displayed an expression profile both contiguous with
      that of flk-1, and also in tissues found some distance from the flk-1-expressing
      endothelium. These results suggest a possible dual role for VEGF which includes a
      chemotactic and/or a cellular maintenance role for VEGF during vascularization of
      the mouse embryo.

PMID- 7647377
TI  - Inhibitory effects of ouabain on early heart development and cardiomyogenesis in
      the chick embryo.
AB  - Pericardial cavity formation and epithelialization of the cardiac precursor cell
      population constitute a critical developmental period that precedes stable
      cardiac cell commitment and differentiation. These events delineate the
      myocardial and endocardial precursor population in the embryo. Restriction of
      Na/K-ATPase (the sodium pump) expression to the pre-cardiomyocyte lateral
      membranes coincides with these events. Na/K-ATPase has been implicated
      developmentally in cavitation and in maintaining membrane potential. Experiments
      were undertaken to determine if the effects of perturbing sodium pump activity
      will affect pericardial cavity formation and, in turn, whether heart formation
      and/or cardiac cell commitment will be affected. We incubated whole chick embryos
      in vitro between stages 5 to 8 in the presence of the highly specific Na/K-ATPase
      inhibitor ouabain. Exposure of whole embryos to 10 microM ouabain (10(-5) M)
      demonstrated that heart development and precardiomyocyte differentiation are
      inhibited principally between stage 5 through stage 7. In each stage the degree
      of inhibition follows a rostrocaudal gradient as development proceeds along the
      anterior to posterior axis. After stage 8 ouabain no longer affects heart
      development or cardiomyogenesis. The inhibition is concentration- and
      developmental stage-dependent. The inhibition is reversible by elevating the
      outside potassium ion concentration [Ko] in the culture medium or by transferring
      the embryos into normal medium minus ouabain even after 20 hr of ouabain
      exposure. The results also suggest that the regulation of the formation of the
      three-dimensional organ is independent from regulation of myogenesis.

PMID- 7647378
TI  - The haemostatic effectiveness of autologous platelet rich plasma sequestered
      after heparin administration and institution of cardiopulmonary bypass.
AB  - Preoperative harvesting and postoperative reinfusion of autologous platelet rich
      plasma (PRP) has been reported to decrease blood loss as well as the requirement
      for homologous blood transfusion following cardiopulmonary bypass (CPB). We have
      developed a technique of intraoperative PRP sequestration which occurs during the
      initial period of CPB after the patient's circulation is supported and heparin
      has been given (PRP+). This process does not require any additional hardware,
      personnel or expense and it is performed without difficulty or complication. To
      evaluate the effect of PRP+ sequestration and reinfusion on blood loss and
      homologous blood requirement after CPB, we randomly assigned 126 consecutive
      patients undergoing elective open heart surgery into the experimental group 1
      (PRP+) (n = 64) or the control (no platelet pheresis) group 2 (n = 52). A third
      group (n = 10) were not included in the randomization. Patients in group 3 had
      PRP prepared by conventional techniques (PRPc) prior to heparin administration
      and given to the patient after protamine infusion. Aggregation and activation
      studies were performed on the PRP+, PRPc, and blood bank platelets (BBP). Per
      cent aggregation of PRP in response to ADP was superior to that of BBP. There
      were no significant differences in ADP induced aggregation between PRP+ and PEPc.
      There was no significant difference in platelet activation (CD62) or number
      between the three groups. Patients infused with PRP+ showed significantly
      increased aggregation to ADP when compared with untreated patients 120 minutes
      after return to the ICW. Furthermore, more homologous haemostatic components
      (platelets/fresh frozen plasma) were required in the control group. We have
      demonstrated that collection of autologous PRP+ after administration of heparin
      does not interfere with its haemostatic effectiveness compared with PRPc prepared
      before the initiation of bypass. Moreover, this can be performed universally in
      haemodynamically unstable patients without any additional costs.

PMID- 7647381
TI  - Insularity and professional protectionism or matrixing and professional security
      in the provision of perfusion services.

PMID- 7647380
TI  - Fluorocarbon emulsions.
AB  - Perfluorocarbon emulsions have been the topic of intense investigation for many
      years and presently there are still no absolute indications for their use in
      clinical practice. The relatively disappointing results of the early clinical
      studies, as a consequence of using low concentrations of a relatively
      underdeveloped emulsion, have been responsible for a largely negative impression
      and it is now essential that the newer second generation emulsions should be
      judged individually with regard to their efficacy and toxicity under different
      circumstances. Technological advancement in the fields of chemistry and
      detergent/emulsifier research will continue and new formulations are being
      developed which which will require to be tested in models in the laboratory. In
      the future, this class of drugs will continue to be the topic of intense
      investigation and their mechanisms of action, which are undoubtedly more complex
      than the simple carriage of dissolved gases in solution, will be clarified.
      However, whether fluorocarbon emulsions will ever be used as a 'blood substitute'
      as was originally anticipated is doubtful.

PMID- 7647382
TI  - Re-inventing the wheel; the use of autologous and fresh donor blood in cardiac
      surgery.
AB  - From the opening of a new cardiac surgical programme in November 1992, autologous
      and fresh donor blood (FDB) were used rather than cold stored blood (CSB)
      wherever possible in patients undergoing operations involving the use of
      cardiopulmonary bypass (CPB). In the first 250 consecutive patients, autologous
      blood was used in 168 (67.2%), fresh blood was used in 188 (75.2%). A total of
      740 units of fresh blood were obtained on the day of operation (mean 3.9 +/- 1.6
      units per patient able to supply donors; 4.9 +/- 1.7 units in the 147 who
      received fresh blood) and 728 units of stored blood were used (mean 3.08 +/- 1.84
      units per patient where fresh blood was used; 6.2 +/- 2.5 units in the 114 where
      no fresh blood was used). The use of autologous blood significantly reduced FDB
      and CSB requirements (p < 0.001), was associated with a shorter intensive care
      and total postoperative stay (p = 0.006 and p = 0.033 respectively), even though
      there were more urgent and emergency cases in this group (p = 0.009) and no
      significant difference in chest drainage. Coagulopathy developed in 41 patients
      (16.4%) and was significantly associated with bypass time (p = 0.0001) and
      preoperative renal dysfunction (p = 0.005), although not with advanced age, sex,
      redo operation, diabetes or glucose-6-phosphate dehydrogenase deficiency.
      Patients with coagulopathy had significantly more transfused blood and blood
      products (p = 0.0001) and longer intensive care and total postoperative stays (p
      = 0.0001). In terms of blood conservation, the use of autologous blood was of
      primary importance.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7647379
TI  - Pulsatile flow during cardiopulmonary bypass speeds thermal energy transfer: a
      possible explanation for the reduced afterdrop.
AB  - The instantaneous thermal energy balance and rates of thermal energy transfer
      during hypothermic cardiopulmonary bypass were measured for a group of patients
      receiving continuous flow and compared with a group receiving pulsatile flow.
      Cooling was more rapid and the rate of thermal energy delivery during rewarming
      significantly greater in the pulsatile flow group despite similar rewarming
      times. The final thermal energy balance at the end of cardiopulmonary bypass was
      larger and the period of postoperative hypothermia shorter in those receiving
      pulsatile flow. The greater rate of thermal energy transfer may explain the
      reduced afterdrop.

PMID- 7647383
TI  - Stuttering therapy with British-Asian children. I: A survey of service delivery
      in the United Kingdom.
AB  - The results of a UK survey of speech and language therapy services offered to
      Asian children and adolescents who stutter are set in the context of current
      therapy approaches favoured in the UK. Eighty-seven speech and language
      therapists from the major centres of Asian population in the UK completed a
      postal questionnaire. This yielded data on: service delivery to stuttering
      children in general; the size and nature of the Asian populations served;
      therapists' own cultural backgrounds; steps taken by therapists to increase their
      skill in this area; interpreter services available; changes made to usual working
      practices aimed at accommodating the cultural needs of Asian clients. The results
      revealed a service mostly provided by non-specialist therapists, who treated
      small numbers of both stuttering and Asian clients. Therapists were serving
      clients from up to four different cultural and linguistic backgrounds, yet access
      to interpreter services was poor. Therapists were on the whole poorly trained and
      equipped to treat Asian clients. A range of changes to working practices are
      described, but no cohesive approach was apparent. The issues involved in
      appropriate and accessible service delivery are discussed.

PMID- 7647384
TI  - Stuttering therapy with British-Asian children. II: Speech and language
      therapists' perceptions of their effectiveness.
AB  - This paper tested hypotheses arising from the literature on the treatment of
      stuttering in British-Asian children and adolescents, using data obtained from a
      postal questionnaire completed by 87 therapists. The results showed therapists
      treating lower numbers of Asian clients than expected, but perceiving their
      therapy to be less effective with their Asian clients than with their British
      ones. The variables affecting therapists' perceived success were not those
      expected. Greater experience with Asian clients did not increase perceived
      success, nor did Asian therapist and client sharing broadly the same cultural
      background guarantee success. A satisfactory interpreter service did not lead to
      a higher perceived success rate, nor did postgraduate training or making special
      changes to usual working practices. On the contrary, therapists in the last two
      categories were less likely to perceive success with their Asian clients.
      Therapists identified a very wide range of cultural factors needing special
      consideration in therapy, but consensus centred around parental attitudes to
      stuttering and to therapy.

PMID- 7647385
TI  - Speech intelligibility in tone language (Chinese) laryngectomy speakers.
AB  - Tone language speakers use lexical tone or fundamental frequency to signal
      meaning. Therefore, native tone language alaryngeal speakers encountering
      difficulty imparting lexical tone variation would suffer loss of speech
      intelligibility. This study examines the intelligibility of lexical tone produced
      by four different alaryngeal speech methods, namely: oesophageal speech,
      electrolarynx, a pneumatic device and tracheo-oesophageal speech. Isolated and
      embedded monosyllabic Chinese words produced by 53 alaryngeal speakers were
      presented to three normally hearing, young adult listeners with no prior exposure
      to laryngectomy speech. The listeners transcribed the speech orthographically.
      Significant differences were found in the intelligibility level between the
      different speech methods. Listeners' responses were also pooled together and
      analysed for tone and segmental errors. Errors of tone alone were found to occur
      more often than segmental errors.

PMID- 7647386
TI  - The motor planning abilities of phonologically disordered children.
AB  - The motor planning abilities of three subgroups of speech-disordered children
      were compared to normally speaking age- and comprehension-matched controls. There
      were 10 phonologically delayed children who used sound-pattern errors typical of
      chronologically aged younger children (delayed group); 10 children whose
      phonological system was characterised by the consistent use of non-developmental
      phonological processes (deviant consistent group); and 10 children whose
      production of specific lexical items and phonological features was variable
      (inconsistent group). The groups were compared on tasks that assessed simple and
      complex motor planning for hand movements and expressive and receptive novel-word
      learning. The groups did not differ on a simple task of motor planning for hand
      movements. However, the inconsistent group performed more poorly than all the
      other groups on a more complex, timed motor-planning task. Although the groups
      performed equally well on a task assessing receptive novel-word learning, the
      inconsistent group performed more poorly than all the other groups on an
      expressive novel-word learning task. The results provide support for the
      hypothesis that speech-disordered children with different surface error patterns
      have different underlying deficits in the speech-processing chain. Specifically,
      inconsistent error patterns are associated with a deficit in some aspects of fine
      motor planning.

PMID- 7647387
TI  - Preliminary evidence on the question of gender differences in language testing of
      older people.
AB  - The effect of gender on the outcomes of language assessments in older people is
      relatively unknown. This study compared the performance of groups of normal older
      men and women on three different batteries of language and memory tests. No
      significant mean score difference was found. All three batteries therefore show
      no strong quantitative gender bias and can be applied equally to older men and
      women with communication difficulties. Although no quantitative gender difference
      was found, the data suggested two possible areas for further investigation (error
      types and interpersonal styles) which may have clinical implications.

PMID- 7647388
TI  - Speech disorders in children treated for posterior fossa tumours: ataxic and
      developmental features.
AB  - The oromotor and speech abilities of 19 children (14 boys and five girls) who had
      been treated for posterior fossa tumour were evaluated using three assessment
      procedures. All subjects completed the Frenchay Dysarthria Assessment and the
      Fisher-Logemann Test of Articulation Competence. Perceptual analyses were also
      performed on the subjects' connected speech samples. Based on the three
      assessment procedures, 11 of the 19 tumour subjects were judged to be speech
      disordered. The 11 speech-disordered subjects were then compared to a control
      group matched for age and sex to determine the nature and severity of speech
      abnormalities which may occur subsequent to the treatment of posterior fossa
      tumour in childhood. Both developmental and dysarthric features were identified
      in the speech of the 11 tumour subjects. The deviant speech characteristics
      exhibited by the tumour subjects included imprecise consonants, excess stress and
      reduced intelligibility, as well as the retention of developmental phonological
      processes. These features are described in detail and discussed with reference to
      descriptive studies of adult dysarthria. An interaction between acquired and
      developmental disorders of speech is proposed.

PMID- 7647389
TI  - Developing AAC technologies: a personal story and philosophy.
AB  - Research into and development of augmentative and alternative communication (AAC)
      technologies is an exciting but complex field. The development of a
      technologically based system which will be an alternative to, or will augment,
      the speech modality for the interpersonal communication needs of people with
      communication dysfunction is not an easy task. This is only a young field and
      thus much of the research methodology is not yet well defined. It is also a
      growing field, and one to which we would wish to attract new practitioners, and
      provide appropriate guidance to them. In any technological development project,
      it is important to define clearly a number of parameters of the project. These
      are: the client group; the knowledge base needed to solve the problems; the
      potential technologies that will help and their characteristics; and the time
      scales envisaged for completion of the research. The authors have been part of a
      research team working in this field for many years, and, in this paper, they will
      examine three research strategies which they have found particularly beneficial,
      illustrating the concepts discussed mainly by reference to personal experiences.
      The paper concentrates on a relatively narrow definition of technology-that which
      is often referred to as 'high technology' or information technology. This is not
      to deny, in any way, the importance to the AAC field of solutions based on other
      technology, and the authors would hope that some of the comments in the paper are
      also appropriate to researchers who are working with systems and techniques which
      do not depend on these technologies.

PMID- 7647390
TI  - Phonetic variation in dysarthric speech as a function of sampling task.
AB  - Previous studies have demonstrated a number of ways in which normal speakers'
      phonetic performance varies across reading and spontaneous speech tasks. This
      study set out to investigate whether similar differences across speech sampling
      tasks were found in a mixed group of dysarthric subjects. A selection of
      segmental and prosodic parameters were investigated acoustically in the
      performance of five mild dysarthric speakers and five matched control subjects.
      The results demonstrated that breath-pause position, unstressed vowel duration
      and voice-onset time were subject to variation across sampling task in the speech
      produced by different types of dysarthric speaker. The results suggest that read
      material produced by dysarthric speakers may not be wholly representative of
      those speakers' spontaneous speech. Preliminary implications for clinical
      practice are discussed. The findings point to the need for further research to
      investigate the extent of such differences and their implications for dysarthria
      assessment, which up to the present has relied predominantly on read material.

PMID- 7647391
TI  - Reading too little into reading?: strategies in the rehabilitation of acquired
      dyslexia.
AB  - This paper examines four recent therapy studies, two involving deep dyslexic
      patients and two involving surface dyslexic patients. These studies illustrate
      that remediation of aspects of acquired dyslexia can have positive benefits for
      the patients concerned which often extend beyond an improvement in reading aloud.
      It is argued that, although it may not be immediately apparent, the remediation
      of acquired reading impairments (and even of reading aloud) can be of functional
      significance for an aphasic subject.

PMID- 7647392
TI  - Impaired tongue strength and endurance in developmental verbal dyspraxia: a
      physiological analysis.
AB  - Tongue strength and endurance measures were obtained from six children with
      developmental verbal dyspraxia (DVD) aged between 5;6 years and 11;5 years and
      compared to those achieved by six normal speaking controls matched for age and
      sex. The instrument for measuring tongue strength comprised an air-filled soft
      rubber bulb connected to a pressure transducer. The results indicated that the
      DVD group had weaker lingual musculature than the controls. In addition the DVD
      subjects exhibited significantly reduced tongue strength endurance compared with
      the controls. Overall the findings support the hypothesis that a motor impairment
      forms at least part of the basis of DVD and may be indicative of the presence of
      a concomitant dysarthria in children with DVD, or may reflect an
      underspecification of the motor programme. The need for revision of contemporary
      taxonomies relating to childhood motor speech disorders is discussed.

PMID- 7647393
TI  - Symptoms of communication breakdown in dementia: carers' perceptions.
AB  - The breakdown of applied communication skills associated with the cognitive
      communication deficit of dementia is poorly documented, as is carers' awareness
      of the nature of the problems. This study considered 32 symptoms which may be
      associated with breakdown of communication. Perceptions of these symptoms by
      carers of 79 community-living dementia patients were compared with perceptions of
      family/close friends of a comparable group of 76 control subjects. Communication
      skills of dementia patients were perceived to be significantly more impaired than
      those of control subjects. Areas of greatest discrepancy between performance of
      dementia and control groups included 'Asking the same question a number of
      times', 'Difficulty following conversation when a group of people are talking',
      'Trouble keeping a conversation going' and 'Struggling to think of the names of
      people and places'. Eleven of the 32 symptoms were reported as occurring 'fairly
      often', 'usually' or 'always' in at least 50% of the dementia patients.
      Identification of specific factors likely to contribute to breakdown of
      communication in dementia will enable involved professionals to guide carers
      towards a better understanding of the problems. This should help to alleviate
      domestic stress thereby enhancing the quality of life of patients and their
      carers.

PMID- 7647394
TI  - Impaired oral-motor function in children with Down's syndrome: a study of three
      twin pairs.
AB  - Three twin births occurring within 18 months in Oxfordshire, in which a girl with
      Down's syndrome was twin to an unaffected boy, provided an opportunity for a
      closely matched comparison of ratings on the Schedule for Oral Motor Assessment,
      which examines oral-motor function in a systematic and reliable way. A detailed
      description of the video-recording of one twin pair is included. This illustrates
      abnormalities of oral-motor function which may occur generally in Down's
      syndrome, as suggested further by a numerical tabulation of the differences found
      between the twins.

PMID- 7647395
TI  - Changes in the hepatitis B virus precore and core regions in association with the
      disappearance of hepatitis B e antigen in patients with chronic hepatitis B.
AB  - Disappearance of the hepatitis B e antigen (HBeAg) typically signals the
      remission of chronic hepatitis B; however, HBeAg defective variants have been
      identified in patients with HBeAg negative chronic hepatitis (CH). We studied the
      changes in the hepatitis B virus (HBV) genome associated with HBeAg clearance in
      four asymptomatic carriers (ASC) and in four patients with CH. Three ASC had a
      precore stop codon variant with the core region being wild-type or deleted. The
      other ASC had wild-type precore and core region. In all ASC, HBV levels were
      reduced markedly with two ASC converting HBV negative status via polymerase chain
      reaction. In contrast, patients with CH had continued high titers of HBV. In two
      patients, the precore region remained wild-type, but the core region contained a
      cleavage site mutation or was deleted. The precore variant was present in both
      ASC and CH, perhaps suggesting that it does not significantly influence hepatitis
      B activity.

PMID- 7647396
TI  - Genetic analysis of a family of lactate dehydrogenase A subunit deficiency.
AB  - Lactate dehydrogenase A subunit (LDH-A) deficiency is an inherited metabolic
      myopathy of glycolysis. The severity of this disease varies from case to case. We
      reported non-consanguineous male sibling cases who had severe muscle pain and
      rhabdomyolysis during anaerobic exercise. Genetic analysis revealed 20 base pair
      deletion of the sixth exon of the LDH-A gene. There was no difference in the gene
      abnormality between our patients and previously reported female cases who had
      history of consanguinity and lower degree of symptoms. The differences in disease
      severity were not due to genomic abnormality in our two families.

PMID- 7647397
TI  - Simultaneous measurement of pulmonary diffusing capacity for CO and cardiac
      output by a rebreathing method in patients with pulmonary diseases.
AB  - Pulmonary diffusing capacity for CO (DLCO) and cardiac output (Q) were
      simultaneously measured by a noninvasive rebreathing method (RB) in 15 normal
      subjects and in 60 patients, including cardiac diseases (CD), bronchial asthma
      (BA), chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary
      fibrosis (PF). DLCO and Q were tested by the single breath method (SB) and the
      dye-dilution method (Dye), respectively. DLCO (RB) correlated well with DLCO (SB)
      (r = 0.890, p < 0.001). Q(RB) also correlated well with Q(Dye) (r = 0.909, p <
      0.001). Factors affecting DLCO (RB) were age, height, body surface area, O2
      consumption, Q, hematocrit (Het) and Q.Hct, among which Q.Hct was the prominent
      influential determinant. DLCO per lung volume was smaller in COPD and PF than in
      BA or healthy subjects, while, the ratio of DLCO/(Q.Hct) was significantly higher
      in COPD than in PF. Simultaneous measurements of DLCO and Q offer comprehensive
      characterization for functional changes in lung parenchyma.

PMID- 7647398
TI  - Correlation of plasma free thyroxine levels with insulin sensitivity and
      metabolic clearance rate of insulin in patients with hyperthyroid Graves'
      disease.
AB  - Insulin sensitivity, metabolic clearance rate of insulin (MCR-I) and basal
      posthepatic insulin delivery rate (BIDR) were investigated by means of euglycemic
      clamp technique in 8 normal subjects and 8 patients with hyperthyroid Graves'
      disease. The mean (+/- SD) steady-state glucose infusion rate (SSGIR) was lower
      in hyperthyroid Graves' patients than in normal subjects (228.9 +/- 57.0 vs.
      290.9 +/- 49.4 mg/m2/min, p < 0.05). Both MCR-I and BIDR were higher in
      hyperthyroid Graves' patients than in normal subjects (1162.9 +/- 517.1 vs. 463.5
      +/- 103.9 ml/m2/min, p < 0.005; 17.7 +/- 12.6 vs. 3.6 +/- 0.9 mU/m2/min, p <
      0.01, respectively). Plasma free T4 levels showed a close correlation with MCR-I
      (r = 0.77, p < 0.05) and BIDR (r = 0.81, p < 0.05), respectively, in Graves'
      patients. These findings indicate that hyperthyroidism is characterized by not
      only a decrease in insulin sensitivity, but also an increase in basal insulin
      secretion and the metabolic clearance rate of insulin, which are correlated with
      plasma free T4 levels.

PMID- 7647399
TI  - Relationship of haptoglobin polymorphism to malaria in the Solomon Islands.
AB  - Haptoglobin (Hp) polymorphism and its relationship to malaria infections was
      examined in Solomon Islanders under 25 years of age. The slide positive rate for
      malaria was 48% (53/111): Plasmodium vivax (Pv) 21 cases, Plasmodium falciparum
      (Pf) 16 cases and the remaining 16 were a mixture of Pv/Pf/P. malariae. Of 111
      subjects examined, 17% (19 subjects) were ahaptoglobinemic (HpO). No association
      was observed between HpO and parasitemia, gender, anemia, serum insulin-like
      growth factor-1 (IGF-1) level, blood glucose level and enlargement of the spleen.
      These results suggest that malaria may not be the major cause of HpO in the
      people of the Solomon Islands.

PMID- 7647400
TI  - The two-color analysis of the T-lymphocyte subsets in experimental allergic
      neuritis in rats.
AB  - We examined the T-cell subsets in the peripheral blood, spleen and lymph nodes
      during the course of experimental allergic neuritis (EAN) by using two-color
      analysis. In the acute phase, the percentages of CD4+ major histocompatibility
      complex (MHC)-II+ cells and CD8+ MHC-II+ cells in the lymph nodes of EAN rats
      were significantly higher than in the control rats. In the recovery phase, the
      percentage of CD4+ CD45RC+ cells and CD8+ CD45RC+ cells in the lymph nodes in EAN
      rats were significantly higher than in the control rats. However, significant
      changes of the T-cell subsets were not detected in either the spleen or the
      peripheral blood during the course of EAN. These results suggest that CD4+ MHC
      II+ cells, CD8+ MHC-II+ cells, CD4+ CD45RC+ cells and CD8+ CD45RC+ cells may play
      a role in the course of EAN. The relationship between these double staining cells
      and EAN is discussed.

PMID- 7647402
TI  - Bronchoalveolar mast cells in summer-type hypersensitivity pneumonitis: increase
      in numbers and ultrastructural evidence of degranulation.
AB  - To investigate the role of mast cells in the development of summer-type
      hypersensitivity pneumonitis (SHP), which is the most common type of
      hypersensitivity pneumonitis in Japan, bronchoalveolar lavage fluid (BALF) cells
      from 13 patients with this disease was studied by light and electron microscopy.
      The proportion and number of BALF mast cells recovered from SHP patients were
      significantly greater than those from patients with sarcoidosis and from control
      subjects. The BALF mast cells from the SHP patients showed various
      ultrastructural changes such as the transformation of granules, cytoplasmic
      vacuolation, and an increase of lipid droplets. These findings appeared to
      reflect activation and degranulation of bronchoalveolar mast cells, suggesting
      that mast cells play a role as inflammatory cells in the development of SHP.

PMID- 7647403
TI  - Renal dysfunction in multiple myeloma.
AB  - This study aims to determine the clinical factors that may affect renal function
      and patient survival in 82 multiple myeloma patients. The patients were divided
      into 3 groups according to their renal function during the initial 8 weeks after
      diagnosis: Group I, 54 patients with serum creatinine (S-Cr) < 177 mumol/L; Group
      II, 11 with S-Cr > or = 177 mumol/L and receiving no dialysis; Group III, 17
      undergoing dialysis treatment. Clinical status at diagnosis, subsequent renal
      function and patient survival were compared. Bence Jones proteinuria (BJP) was
      found in all patients in Groups II and III, compared to 67% of patients in Group
      I (p < 0.05, I vs II or III). Hypercalcemia, hyperuricemia and intravenous
      administration of contrast medium, together with BJP each constituted independent
      risk factors of renal dysfunction. The incidence of hypercalcemia in Group II was
      significantly higher than in the other 2 groups. Patient survival was 26.8 +/-
      23.7 months in Group I, 8.1 +/- 10.3 in II and 12.1 +/- 16.6 in III (p < 0.05, I
      vs II or III). Renal function and patient survival depended on the initial renal
      function. Renal function was likely compromised in the presence of BJP.

PMID- 7647401
TI  - OK-432 induces production of neutrophil chemotactic factors in malignant pleural
      effusion.
AB  - We investigated the changes in cellular components and neutrophil chemotactic
      factors in pleural fluid from 19 lung cancer patients who received intrapleural
      injection of OK-432 to treat malignant pleurisy. Not only neutrophil chemotactic
      activity (NCA) but also neutrophil count and percentage were increased
      significantly at 6 hours after OK-432 injection. The neutrophil count was
      significantly correlated with NCA level. The levels of C5a and IL-8 in pleural
      fluid were increased significantly after OK-432 injection. The increased IL-8
      level was associated with a increase of both NCA and neutrophil count. OK-432
      treatment also induced a marked increase of IL-1 beta and IL-6 in pleural fluid.
      Thus, intrapleural injection of OK-432 induced production of neutrophil
      chemotactic factors (IL-8 and C5a) and cytokines (IL-1 beta and IL-6), which
      eventually attracted neutrophils into the pleural space. These observations
      suggest that neutrophil migration mediated by these factors and cytokines may
      contribute to the sclerosing effects of OK-432 treatment.

PMID- 7647405
TI  - Hb Gunma (beta Gunma) with pulmonary embolism.
AB  - A 67-year-old woman with pulmonary embolism was suspected to have beta
      thalassemia based on microcytosis, hemolysis and a negative red cell stability
      test. The DNA sequencing analysis of beta-globin gene, however, revealed the
      deletion of three nucleotides within codon 127-128, leading to substitution of
      glutamine and alanine residues at 127 and 128 by proline, namely Hb Gunma. This
      mutant is characterized by the fact that no abnormal hemoglobin is detected in
      the circulating blood, and is classified as a thalassemic hemoglobinopathy. The
      present case showed a relatively hemolytic manifestation.

PMID- 7647404
TI  - Ten-year follow-up study of thyroid function in euthyroid patients with simple
      goiter or Hashimoto's thyroiditis.
AB  - In an attempt to study the natural course of Hashimoto's thyroiditis and simple
      goiter, 74 euthryroid patients with Hashimoto's thyroiditis and 212 patients with
      simple goiter were followed for 10 years. In 204 patients with simple goiter
      (96.2%) it remained as a simple goiter throughout the observation period, whereas
      8 patients (3.8%) later had Hashimoto's thyroiditis as evidenced by the
      appearance of circulating thyroid autoantibodies. These 8 patients had HLA typing
      significantly different from that of control subjects. None of the patients with
      simple goiter had hyperthyroid Graves' disease despite the fact that 17.5% of
      those patients had mild to moderate exophthalmos with either Moebius' sign or von
      Graefe's sign. In contrast, 12 patients with Hashimoto's thyroiditis (16.2%) had
      exophthalmos with Moebius' sign and/or von Graefe's sign, and 4 of 12 such
      patients later had hyperthyroid Graves' disease. TSH binding inhibitory
      immunoglobulin was detected in 3 of 4 such patients with hyperthyroid Graves'
      disease. Forty-nine patients with Hashimoto's thyroiditis (66.2%) still remained
      euthyroid but 20 of those (27.0%) turned into hypothyroidism during the 10-year
      follow-up.

PMID- 7647406
TI  - Fat embolism syndrome caused by vegetable oil injection.
AB  - We present a case of fat embolism syndrome following vegetable oil injection for
      augmentation mammaplasty. Although vegetable oil is a stable neutral fat under
      usual storage conditions, it caused fat embolism and pulmonary injury in this
      patient. We investigated this mechanism by compound analysis of the injected oil,
      transbronchial lung biopsy and special staining of alveolar macrophages. This is
      the first description of the human response to vegetable oil injection. These
      data should aid in the investigation of the side effects of many types of lipids
      which may be applied to humans for various purposes in the future.

PMID- 7647408
TI  - Occult thymic carcinoma presenting as malignant cardiac tamponade.
AB  - A 66-year-old woman who presented with malignant cardiac tamponade of unknown
      origin was eventually found to have a tiny squamous cell carcinoma of the thymus.
      Thus, even a small thymic carcinoma can exhibit highly aggressive behavior. It
      should be included in the differential diagnosis of malignant cardiac tamponade
      of unknown origin.

PMID- 7647407
TI  - A rapidly progressive case of interstitial pneumonia.
AB  - We treated a 51-year-old woman who had rapidly progressive respiratory distress
      with an interstitial shadow on chest roentgenogram. Pathologically, open lung
      biopsy specimens showed an acutely changed lesion such as interstitial
      inflammatory thickening, polypoid intraluminal organizing exudates, and also
      honeycombing which was not recognized on chest computed tomogram. These findings
      were considered unconformable to acute interstitial pneumonia (AIP),
      bronchiolitis obliterans organizing pneumonia (BOOP), and also usual interstitial
      pneumonia, although the clinical diagnosis was AIP or BOOP. We diagnosed a
      rapidly progressive interstitial pneumonia showing an acute lung injury pattern
      like AIP and BOOP. She showed significant recovery with corticosteroid and
      cyclophosphamide.

PMID- 7647409
TI  - Three cases of primary hyperparathyroidism associated with nonmedullary thyroid
      carcinoma.
AB  - Nonmedullary thyroid carcinoma was diagnosed in three of nine cases of primary
      hyperparathyroidism. In all three cases, diagnosis of primary hyperparathyroidism
      was made before that of thyroid carcinoma. In the first case, follicular
      carcinoma was incidentally detected during parathyroidectomy. In the second case,
      thyroid tumor was discovered during imaging studies for hyperparathyroidism.
      Papillary carcinoma and ectopic parathyroid was diagnosed postoperatively. In the
      third case, a thyroid lesion had been mistaken for a putative parathyroid lesion,
      but the diagnosis of papillary carcinoma was obtained. These cases suggest that
      preoperative examination for hyperparathyroidism should be carefully evaluated,
      considering possible concomitant thyroid lesions.

PMID- 7647411
TI  - Ectodermal dysplasia syndrome in siblings with true keloids, stenosis of the
      esophagus after operations for congenital achalasia and renovascular hypertension
      due to stenosis of renal artery.
AB  - Ectodermal dysplasia syndrome (EDS) is a rare hereditary disease, with symptoms
      brought about by dysplasia of ectodermal tissue (such as skin, teeth, nails, and
      hair). This report details the cases of two siblings (41 and 43 year old sisters)
      with autosomal recessive and hydrotic EDS complicated by esophageal achalasia,
      postoperative stenosis of esophagus, true keloids, renovascular hypertension,
      incomplete malrotation of the bowel, and demyelination of the brain.

PMID- 7647410
TI  - Effect of octreotide on ventilation and dyspnea sensation in a patient with
      cirrhotic hypoxemia.
AB  - We examined the long-term effects of octreotide, a somatostatin analogue, on
      ventilation in a case of cirrhotic hypoxemia. After daily administration of
      octreotide for one month, the dyspnea on exertion was notably ameliorated,
      although pulmonary gas exchange was only slightly improved. The octreotide
      therapy reduced the hypoxic ventilatory drive, which may be one reason for the
      relief of the dyspnea sensation.

PMID- 7647412
TI  - Insulin autoimmune syndrome after the third therapy with methimazole.
AB  - In 1986, a 26-year-old female had been diagnosed as having Graves' disease and
      had been treated with methimazole for four months. After the treatment with
      propylthiouracil for another four months, she had been treated with methimazole
      once again. She was in complete remission for two years. She again experienced
      symptoms of hyperthyroidism, and treatment with methimazole was started again. On
      the thirteenth day after treatment, she experienced hypoglycemic attacks with
      skin eruption. The plasma glucose was 57 mg/dl, 125I-Insulin binding 69%, free
      IRI 196 microU/ml. The patient had the HLA-DRB1*0406.

PMID- 7647414
TI  - Immunoblastic lymphadenopathy-like T-cell lymphoma displaying rearrangement of
      both IgH and TCR beta genes after 4-year follow-up of idiopathic eosinophilia.
AB  - Immunoblastic lymphadenopathy (IBL)-like T-cell lymphoma (IBL-T) occurred in a 60
      year-old female after a 4-year follow-up of idiopathic eosinophilia and upper
      pharyngeal inflammatory tumor with infiltration of mature eosinophils. Gene
      analysis of tumor cells revealed rearrangement of both IgH and TCR beta genes.
      The patient died of lymphoma seven months after the onset of the illness, in
      spite of chemotherapy against lymphoma. The relationship between eosinophilia and
      the pathogenesis of IBL-T, as well as the significance of the rearrangement of
      both IgH and TCR beta genes are discussed.

PMID- 7647413
TI  - Familial thyroxine-binding globulin deficiency associated with hyperthyroidism.
AB  - A 24-year-old woman with familial thyroxine-binding globulin (TBG) deficiency
      associated with hyperthyroidism is reported. Thyroid-stimulating hormone (TSH)
      binding inhibitor immunoglobulin (TBII) was negative, whereas thyroid-stimulating
      antibody (TSAb) was positive. Serum thyroxine-binding globulin (TBG) levels were
      extremely low, and remained low even after the normalization of thyroid function
      with methimazole (MMI) treatment. The serum TBG level of the mother of patient
      was also below the normal lower limit. Genetic analysis revealed single
      nucleotide deletion, common among Japanese with complete TBG deficiency (TBG-CD),
      from the allele-specific amplification of the TBG genes of the patient.

PMID- 7647415
TI  - Localized myxedema, associated with increased serum hyaluronic acid, and response
      to steroid pulse therapy.
AB  - A 66-year-old man presented with Graves' disease and widespread localized
      myxedema. Extensive lesions were present on the legs, feet, hands, and face. TSH
      receptor antibody (TBII) was markedly positive and the serum hyaluronic acid
      level was very high. Intravenous steroid pulse therapy was followed by oral
      therapy with gradual tapering. This regimen markedly improved the skin lesions
      and resulted in a decrease of the serum hyaluronic acid level. The findings
      suggest that steroid pulse therapy is effective for the treatment of extensive
      localized myxedema. In addition, the serum hyaluronic acid level may be a useful
      parameter for the follow-up of patients with this condition.

PMID- 7647417
TI  - Vasospastic angina pectoris associated with apical hypertrophic cardiomyopathy.
AB  - As the chest symptoms and electrocardiographic changes of hypertrophic
      cardiomyopathy are occasionally very similar to those of angina pectoris, there
      are some difficulties in the diagnosis and treatment of cases of ischemic heart
      disease associated with hypertrophic cardiomyopathy. Here we report a case of
      vasospastic angina pectoris associated with hypertrophic cardiomyopathy diagnosed
      by coronary spasm provocation test performed by intracoronary administration of
      acetylcholine. In the treatment of such cases, beta blockers, which have the
      effect of decreasing the oxygen demand of the heart and the potential to induce
      coronary spasm, must be administered carefully.

PMID- 7647416
TI  - Fulminant Mycoplasma pneumoniae pneumonia with marked elevation of serum soluble
      interleukin-2 receptor.
AB  - We treated a married couple who developed Mycoplasma pneumonia at the same time,
      and whose clinical courses and serum soluble interleukin-2 receptor (sIL-2R)
      levels were markedly different. The 30-year-old wife developed acute respiratory
      failure and her sIL-2R levels were extremely increased. After pulse therapy, her
      clinical state was improved, with a marked decrease in sIL-2R. In contrast, the
      36-year-old husband, also suffered from the pneumonia with a moderate increase of
      sIL-2R, and recovered without any complications. The difference in their clinical
      states may be reflected in their serum sIL-2R levels, a marker of T cell
      activation in vivo.

PMID- 7647418
TI  - Partial type of common atrioventricular canal defect associated with mitral
      stenosis.
AB  - We report a 63-year-old woman, with a partial type of common atrioventricular
      canal and mitral stenosis, who was hospitalized because of dyspnea on exertion.
      Two-dimensional echocardiogram showed an ostium primum atrial septal defect with
      two well-formed AV valves located at the same level. However, both anterior and
      posterior mitral leaflets were markedly thickened with a thickened subvalvular
      apparatus, and the commisures were fused. Echocardiographic measurements
      demonstrated a mitral valve area of 1.48 cm2 with mild mitral regurgitation.
      Cardiac catheterization demonstrated mild pulmonary artery hypertension with a
      large left to right shunt (72%) at the atrial level. The combination of the
      partial type of common atrioventricular canal and mitral stenosis is rare; only
      one similar case has been reported previously in the literature.

PMID- 7647419
TI  - Non-cushingoid Cushing's syndrome due to adrenocorticotropic hormone-independent
      bilateral adrenocortical macronodular hyperplasia.
AB  - This case report describes a 68-year-old man with Cushing's syndrome due to
      adrenocorticotropic hormone (ACTH)-independent bilateral adrenocortical
      macronodular hyperplasia (AIMAH). He was referred to our hospital for evaluation
      of bilateral enlargement of the adrenal glands found incidentally by computed
      tomography (CT). He had a ten-year history of hypertension. Although he was
      normokalemic and did not show Cushingoid features, the diagnosis of ACTH
      independent Cushing's syndrome was established by endocrinological examinations.
      His plasma cortisol showed no diurnal rhythm and was unsuppressible by high-dose
      (8 mg/day) dexamethasone. Plasma ACTH was undetectable and did not respond to
      corticotropin-releasing hormone. Excised adrenal glands were markedly enlarged
      (right 28 g and left 64 g). Macroscopic appearance of the glands showed multiple
      yellowish nodules typical for AIMAH; microscopic findings were also compatible
      with AIMAH. The present case indicates that patients with AIMAH sometimes do not
      show typical Cushingoid features and therefore AIMAH can be found incidentally
      from ultrasound or CT examination of the abdomen.

PMID- 7647420
TI  - Primary biliary cirrhosis (PBC)-CREST (calcinosis, Raynaud's phenomenon,
      esophageal dysfunction, sclerodactyly and telangiectasia) overlap syndrome
      complicated by Sjogren's syndrome and arthritis.
AB  - A 36-year-old woman with primary biliary cirrhosis (PBC)-CREST (calcinosis,
      Raynaud's phenomenon, esophageal dysfunction, sclerodactyly and telangiectasia)
      overlap syndrome complicated by Sjogren's syndrome and arthritis is reported. She
      had suffered from Raynaud's phenomenon, sclerodactyly, morning stiffness,
      arthralgia and sicca symptoms since 34 years of age. She exhibited an increased
      level of alkaline phosphatase and hyperglobulinemia at 2.8 g/dl without any
      symptoms, and histological findings from the biopsy specimen of the liver were
      consistent with those of PBC. Her human leukocyte antigen (HLA) typing was DR8
      homozygous.

PMID- 7647421
TI  - Takayasu's arteritis in prepulseless stage manifesting lymph node swelling and
      hepatosplenomegaly.
AB  - A 17-year-old male had fever of unknown origin (FUO) for 3 months with positive c
      reactive protein, lymph node swelling, and hepatosplenomegaly. Biopsy specimens
      of the liver and lymph node disclosed nonspecific inflammation. Lymph node
      swelling and hepatosplenomegaly subsided gradually, while vascular murmur and
      pulselessness appeared. Computerized tomography and magnetic resonance imaging
      showed thickened arterial wall, while angiography disclosed arterial narrowing.
      From these findings he was diagnosed to have Takayasu's arteritis. The therapy
      with prednisolone was effective. Takayasu's arteritis is rarely manifested by
      hepatosplenomegaly and lymphadenopathy in its prepulseless stage.

PMID- 7647422
TI  - Pentoxifylline treatment in HTLV-I-associated myelopathy.

PMID- 7647423
TI  - Screening for prostate cancer. Implications for drug therapy.

PMID- 7647424
TI  - Defining treatment aims and end-points in older patients with cancer.

PMID- 7647425
TI  - From peptic ulcer disease to NSAID gastropathy. An evolving nosology.
AB  - Nonsteroidal anti-inflammatory drug (NSAID)-induced gastropathy is an important
      clinical entity, most commonly encountered in elderly female patients. The
      expanding use of NSAIDs in the elderly population has led to an increased
      incidence of NSAID-induced gastropathy. The risk of gastric bleeding in these
      patients is 7-fold higher than in the younger population. Long term NSAID therapy
      in the elderly is apparently associated with failure of normal gastric mucosal
      adaptation. Silent unidentified gastric lesions are likely to be common with long
      term NSAID therapy, as symptomatology does not parallel pathological progression.
      This gastropathy, in contrast to peptic ulcer disease, is responsive to
      prostaglandins and other cytoprotective agents. A new generation of prostaglandin
      sparing NSAIDs (e.g. nabumetone), in addition to the older nonacetylated
      salicylates, may represent less gastrotoxic alternatives. Therefore, these agents
      may substantially reduce the risk of NSAID-induced gastropathy. The debate
      continues as to whether to use NSAIDs, and under which circumstances. More
      importantly, the cost-benefit implications and justification for concomitant
      therapy with gastroprotective agents cloud the picture. Currently, there is a
      definite consensus that NSAIDs should not be casually used on a chronic basis,
      especially in patients at risk for serious gastropathy complications. In all
      cases, where possible, gastric prostaglandin-sparing NSAIDs or nonacetylated
      salicylates should be used in lowest effective dosages. In special circumstances,
      gastroprotective co-therapy can be considered. NSAID therapy probably should not
      be used or continued in elderly patients with a history of bleeding ulcers or
      recent major gastric ulcer activity.

PMID- 7647427
TI  - Treatment of oral and nonoral sources of halitosis in elderly patients.
AB  - The increasing number of older patients being seen in medical and dental offices
      in the industrialised world emphasises the need for a thorough understanding of
      the normal aging process. Additionally, close attention must be paid to the
      disease processes that affect this special needs population. Although there are
      many positive psychosocial issues associated with the aging patient, many
      diseases and disabilities associated with the aging process place an increased
      burden on the elderly patient. The relationship between general and oral health
      must be understood by the practitioner if therapies are to be effective. Although
      it is not the objective of this article to provide a comprehensive review of oral
      healthcare, an attempt will be made to provide general information on the
      diagnosis and treatment planning for oral malodours often associated with poor
      oral and/or systemic health. Every healthcare provider treating the elderly
      patient for oral malodours must recognise that there is potentially a direct
      relationship between the oral and systemic health of the patient. While most oral
      malodours have a simple cause, no single therapy is always effective. For best
      results, a team approach to diagnosing and treating oral malodours involves the
      dentist, physician, dietician and pharmacist. This multidisciplinary approach
      should be arranged before the onset of any complex therapy. When indicated,
      supportive, responsible family members should be additionally involved to assure
      patient compliance. The mouth and teeth can be a source of great pride and
      pleasure. A beautiful smile is one of the most pleasant greetings a human can
      offer. Enjoying a meal of fine food and drink is truly gratifying.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7647426
TI  - Influenza vaccination in older patients. Immunogenicity, epidemiology and
      available agents.
AB  - Excess hospitalisation and deaths attributable to influenza virus infections
      often occur during epidemics and even in interepidemic periods. Influenza
      vaccines in current use are inactivated preparations that contain 15 micrograms
      each of the most recently circulating influenza A (H3N2 and H1N1) and B viruses.
      At present, 3 types of inactivated influenza virus vaccines are available: (a)
      whole virus vaccines; (b) split virus vaccines; and (c) subunit vaccines. All 3
      types are similarly immunogenic in primed patients. Vaccine efficacy depends on a
      close antigenic match between the vaccine composition and the influenza strains
      circulating in the human population. The continuous antigenic drift of the viral
      membrane antigens (haemagglutinin and neuraminidase) necessitates an update of
      the vaccine composition each year according to the recommendations of the World
      Health Organization (WHO). Subunit and split virus vaccines cause fewer systemic
      reactions than whole virus vaccines. At present, live attenuated influenza virus
      vaccines are not licensed. In perspective, combined administration of live and
      inactivated vaccines seems to be advantageous. Influenza vaccine is approximately
      75% effective in reducing deaths in elderly and high risk persons. Several
      studies have shown that the antiviral agent amantadine is a useful adjunct to
      vaccination for preventing influenza A in institutional settings. Currently, the
      proper use of inactivated vaccine according to the recommendations of public
      health authorities is the only way to reduce the annual influenza-associated
      medical and economic burden.

PMID- 7647429
TI  - Percutaneous biliary endoscopy.
AB  - The development of small-diameter flexible endoscopes has expanded the role of
      biliary endoscopy to include percutaneous interventions. Percutaneous biliary
      endoscopy is a technique that is easily learned. The equipment for percutaneous
      biliary endoscopy is readily available since most hospitals have an appropriate
      sized choledochoscope and light source for intraoperative use. Therefore, the
      initial capital costs associated with flexible biliary endoscopy are minimal.
      Percutaneous biliary endoscopy in the interventional radiology suite is an ideal
      arrangement to facilitate a wide variety of biliary diagnostic and interventional
      procedures.

PMID- 7647430
TI  - Health care cost-benefit and cost-effectiveness analysis: an overview.

PMID- 7647428
TI  - Osteoarthritis in the aged. Epidemiological issues and optimal management.
AB  - Osteoarthritis (OA) is the most common of the arthropathies. The prevalence
      increases significantly with age, with as many as 68% of women and 58% of men
      aged 65 years or older having radiological evidence of disease. With an aging
      population, OA will represent an increasingly significant healthcare burden. The
      current treatment of patients with OA is purely symptomatic. As yet, there is no
      evidence that treatment changes the course of the disease. The current optimal
      treatment involves a combined approach which includes modification of risk
      factors, particularly obesity, and nonpharmacological treatments such as
      physiotherapy. If drugs are required in the treatment of OA, full dose regular
      paracetamol (acetaminophen) should be the first line of analgesic therapy. There
      is little evidence that the current over-reliance on long term treatment with non
      steroidal anti-inflammatory drugs (NSAIDs) is justified. If NSAIDs are used, it
      is necessary to regularly review their use and to be aware of their potential
      toxicity, particularly in the older age group.

PMID- 7647431
TI  - Iliac artery stent placement with the Palmaz stent: follow-up study.
AB  - PURPOSE: The long-term efficacy of iliac artery stent placement with the Palmaz
      stent was evaluated for treatment of limb ischemia. PATIENTS AND METHODS: Iliac
      stent implantation for limb ischemia was performed on 108 limbs in 83 patients.
      Eighty patients (96.4%) were followed up clinically from 1 to 70 months (mean,
      25.8 months), and 30 patients (37.5%) were followed up with angiography from 1 to
      48 months (mean, 10.4 months). Patients were classified into six categories by
      using an ischemic ranking profile. Clinical success was defined as a minimum one
      category improvement from preprocedure ranking. RESULTS: The clinical success
      rate was 98.9% immediately after the procedure and 86.2% at 48 months. Long-term
      success was statistically more common in patients with higher preprocedure and
      lower postprocedure ischemic ranking, and in patients without diabetes.
      Arteriography demonstrated a primary patency rate of 87.5% at latest follow-up,
      with five occlusions (12.5%) and only two (5.0%) restenoses. Average stenosis was
      17.8% at 6 months and 24.7% at 2 years. Stent restenosis was statistically more
      common with a higher postprocedure pressure gradient. The complication rate was
      9.7%, and 30-day mortality was 1.2%. CONCLUSION: Long-term clinical and
      angiographic follow-up demonstrates iliac artery stent placement with the Palmaz
      stent is safe and efficacious for treatment of limb ischemia.

PMID- 7647432
TI  - Recanalization of femoropopliteal occlusive lesions: a comparison of long-term
      clinical, color duplex US, and arteriographic follow-up.
AB  - PURPOSE: To assess the merits of clinical examination, color-flow duplex
      ultrasound (US), and arteriography in the follow-up of patients who have
      undergone femoropopliteal artery recanalization for occlusive disease. PATIENTS
      AND METHODS: Recanalization of the occluded femoropopliteal artery was attempted
      in 62 patients. Follow- up included clinical examination, ankle-brachial blood
      pressure measurement, and duplex US scanning at 4-month intervals during the
      first year, at 6-month intervals during the second year, and one a year
      thereafter. Failure of recanalization included substantial restenosis or
      reocclusion of the treated segment. Arteriography was performed at the end of the
      first year or earlier if recurrence was suspected. Agreement of clinical findings
      with those of duplex US and those of arteriography was determined with kappa
      statistics; a kappa value of greater than 0.75 represented excellent agreement.
      RESULTS: Recanalization was technically successful in 51 patients (82%). Clinical
      patency was 63% (standard error [SE], 6%) after 1 year, 56% (SE, 7%) after 2
      years, and 46% (SE, 9%) after 3 years. When technical failures were included, the
      patency rate at duplex US was 58% (SE, 6%) after 1 year, 40% (SE, 7%) after 2
      years, and 33% (SE, 8%) after 3 years. The patency rate at arteriography was 53%
      (SE, 7%) after 1 year, 33% (SE, 7%) after 2 years, and 30% (SE, 8%) after 3
      years. When arteriographic examination was considered the standard of reference,
      diagnostic accuracy in the identification of recurrent lesions was 94% at duplex
      US (kappa = 0.88) and 74% at clinical examination (kappa = 0.51). CONCLUSION:
      Rates of restenosis or occlusion detected at follow-up with duplex US and
      arteriography were comparable. However, clinical examination alone helped detect
      fewer cases of recurrent disease.

PMID- 7647433
TI  - Revascularization for chronic mesenteric ischemia: comparison of operative
      arterial bypass grafting and percutaneous transluminal angioplasty.
AB  - PURPOSE: To compare the relative safety and efficacy of the two primary
      techniques for treatment of chronic mesenteric ischemia (CMI): operative bypass
      grafting (OBG) and percutaneous transluminal angioplasty (PTA). PATIENTS AND
      METHODS: Retrospective analysis of hospital charts and angiograms, and
      supplemental telephone follow-up were performed for 17 patients treated for CMI
      between January 1985 and September 1993. Nine patients underwent OBG; eight
      patients underwent PTA (one patient underwent two PTA procedures). RESULTS:
      Technical success was 100% for OBG versus 30% according to angiographic criteria
      for PTA (although 80% had improved luminal diameter). Procedure-related mortality
      was 11% (one of nine patients) for OBG and 13% (one of eight) for PTA. The
      nonfatal major complication rate was 33% (three of nine) for OBG and 25% (two of
      eight) for PTA. Initial pain relief occurred in seven of nine (78%) successful
      OBGs and all of seven (100%) PTA procedures with lumen improvement. Long-term
      pain relief among OBG survivors was complete in seven of eight (88%) and four of
      six (67%) of PTA survivors with CMI (mean follow up, 34.5 and 9.2 months,
      respectively). CONCLUSIONS: Due to the greater durability of results, OBG is
      indicated in patients with low operative risk and classic symptoms and
      angiographic findings of CMI ischemia. PTA is best reserved for patients with
      prohibitive operative risks, classic symptoms, and atherosclerotic stenoses.

PMID- 7647434
TI  - Short-term femoral nerve complications following percutaneous transfemoral
      procedures.
AB  - PURPOSE: To determine the prevalence of transient femoral nerve anesthesia
      following transfemoral angiographic procedures. PATIENTS AND METHODS: Fifty-eight
      patients undergoing a variety of routine transfemoral procedures underwent a
      neurologic assessment within an hour of the procedure. RESULTS: Nine patients
      (16%) were found to have complete or partial deficits in the ipsilateral femoral
      nerve territory. All deficits were transient. CONCLUSIONS: Transient femoral
      nerve deficits are not uncommon following transfemoral procedures. With the
      advent of true outpatient vascular procedures (where the patient may walk away
      after only a 30-minutes recovery period following a transvenous intervention or
      after 60 minutes following arteriography), transient neurologic problems related
      to the infiltration of local anesthetic around the femoral artery assume real
      clinical importance.

PMID- 7647435
TI  - Bronchial artery embolization for hemoptysis in a lung transplant recipient.

PMID- 7647436
TI  - Direct percutaneous coil and ethanol embolization of a celiac artery
      pseudoaneurysm.

PMID- 7647437
TI  - Treatment of aortobiiliac graft stenosis with contralateral Wallstent placement.

PMID- 7647438
TI  - Effect of nonanticoagulant heparin (Astenose) on restenosis after balloon
      angioplasty in the atherosclerotic rabbit.
AB  - PURPOSE: To determine whether intravenous administration of Astenose, a high
      molecular-weight nonanticoagulant heparin, can reduce restenosis following
      balloon angioplasty in a rabbit model. MATERIALS AND METHODS: Focal
      atherosclerosis was induced in 54 rabbits (89 vessel), and angioplasty was
      performed after animals were randomized into five groups. Group 1 vessels
      (control) were treated with lactated Ringer solution for 28 days (n = 19); group
      2, Astenose at 0.10 mg/kg per hour for 28 days (n = 16); group 3, Astenose at
      0.33 mg/kg per hour for 28 days (n = 16); group 4, Astenose at 0.60 mg/kg per
      hour for 28 days (n = 17); and group 5, Astenose at 0.33 mg/kg per hour for 14
      days (n = 21). Arteriograms were obtained to measure minimal luminal diameters
      before, immediately after, and 28 days after angioplasty, and the rabbits were
      killed for histologic analysis. RESULTS: Angiographically demonstrated restenosis
      was significantly reduced in groups 3 (18.9% +/- 3.7, P = .04) and 4 (20.2% +/-
      3.1, P = .04) compared with the control group (32.4% +/- 4.8). Group 5 showed a
      nonsignificant trend toward reduced restenosis (23.1% +/- 2.9, P = .09), and
      group 2 showed restenosis similar to that in group 1 (31.0% +/- 2.5, P = .80).
      However, quantitative histopathologic analysis detected no differences among the
      groups in absolute plaque area. Medial area was significantly smaller in groups 2
      and 5 (P < or = .002) than in group 1, and there was a nonsignificant trend
      toward reduced medial area in groups 3 and 4 (P = .12). CONCLUSION: Long-term
      intravenous Astenose therapy resulted in a modest but statistically significant
      reduction in angiographically demonstrated restenosis after angioplasty in this
      atherosclerotic rabbit model.

PMID- 7647439
TI  - Comparative effectiveness of intravascular stents in resisting arterial
      vasoconstriction: evaluation with use of intact elastic (rabbit aorta) and
      muscular (dog carotid) arteries in an ex vivo model.
AB  - PURPOSE: The ability of three different intravascular stents (Gianturco-Roubin,
      Palmaz-Schatz, and CV Rad), and two different metals (stainless steel and
      tantalum) to resist vasoconstriction was evaluated in an intact artery ex vivo
      model. MATERIALS AND METHODS: Stents were deployed in 21 rabbit thoracic aortae
      and five dog carotid arteries, which were constricted with phenylephrine and
      serotonin, respectively. Vasoconstriction was measured with the use of high
      frequency ultrasonic imaging. RESULTS: The maximal vasoconstriction of the
      control segment was 37.7% +/- 2.6 with rabbit aortae and 36.3% +/- 4.1 with dog
      carotid arteries, while the average maximal constriction for all segments in
      which stents were placed was 5.7% +/- 1.1 (P < .01). The maximal constriction of
      the Gianturco-Roubin stainless steel stent was 9.4% +/- 2.7 versus 7.9% +/- 1.6
      with the tantalum version (P = .65). Both designs showed somewhat greater
      constriction compared with either the Palmaz-Schatz (3.3% +/- 0.9) or the CV Rad
      (1.4% +/- 1.1) stents. CONCLUSIONS: Although all of the stents tested
      substantially resist arterial vasoconstrictive forces, the Palmaz-Schatz and CV
      Rad stents resist vasoconstriction to a greater degree than the Gianturco-Roubin
      stents. Tantalum and stainless steel stents of the same design (Gianturco-Roubin)
      appear similar in their ability to resist vasoconstrictive forces.

PMID- 7647442
TI  - Clinical trial of the Bard CT guide system.
AB  - PURPOSE: The Bard computed tomography (CT) guide holds a Monopty gun within the
      CT gantry and mechanically aids insertion of the needle tip. The clinical
      efficacy and accuracy of this device, its effect on procedure time, and the
      limitations of the device were studied. PATIENT AND METHODS: In a prospective
      study, the outcome of 107 consecutive biopsies performed with 18-gauge needles
      was evaluated. In every patient, an attempt was made to perform the biopsy with
      an 18-gauge Monopty gun positioned with the Bard CT guide and with a hand-held 18
      gauge PercuCut needle. Of 107 patients, 73 underwent biopsy with both devices,
      and 34 underwent biopsy with the PercuCut needle alone. RESULTS: The device could
      not be used in 32% of patients, primarily due to patient size or the need to use
      a lateral approach to a lesion. When the device was used, it positioned the
      needle within +/- 2 degrees of the programmed angle and at the programmed depth
      in 96% of cases on the first attempt; the target lesion was hit in 93% of cases
      (vs 78% with the hand-held needle). Use of the device resulted in a diagnostic
      biopsy in 84% of cases versus 93% with percuCut needle. This difference was not
      statistically significant. CONCLUSION: Despite certain limitations, the Bard CT
      guide is extremely accurate. Its use decreases the number of times a needle must
      be repositioned prior to biopsy, thus it would likely reduce the overall
      procedure time. The diagnostic accuracy of 84% is good and could be improved on
      by immediately evaluating the specimen cytologically and making additional passes
      where necessary.

PMID- 7647441
TI  - Evaluation of a second-generation tantalum biliary stent in a canine model.
AB  - PURPOSE: To evaluate the safety and feasibility of use of a balloon-expandable
      tantalum (Tantaflex) stent in the biliary tree in a canine model. MATERIALS AND
      METHODS: In this prospective, randomized trial, 10 tantalum stents were placed in
      eight dogs (two telescoping stents in two dogs), and six Wallstents were placed
      in six dogs as controls. Stents were deployed into the common bile duct via a
      cholecystostomy at laparotomy under fluoroscopic and cholangiographic guidance.
      Two dogs from each stent group were killed at 4, 12, and 26 weeks; the two dogs
      with telescoping stents were killed at 12 weeks. Premortem patency was confirmed
      cholangiographically. Postmortem stent explants were inspected grossly, and
      tissues were examined histologically. Bacteriologic evaluation of bile was
      performed. RESULTS: All 14 dogs survived until they were scheduled to be killed
      without clinical complication or evidence of jaundice. Patency was demonstrated
      at terminal cholangiography in 12 of 14 dogs and at explantation in 13 of 14
      dogs. One Wallstent placed across the ampulla in a dog killed at 26 weeks became
      obstructed. In another dog, the presence of a cholelith in the cystic duct
      precluded filling of the common bile duct from the cholecystotomy. Only mild
      inflammatory changes were present in the bile ducts. CONCLUSION: The tantalum
      stent can be used safely and effectively in the common bile duct in normal dogs.
      Performance of a clinical trial in humans is supported finding of this study.

PMID- 7647440
TI  - Comparison of Gianturco Z stents and Wallstents in a hemodialysis access graft
      animal model.
AB  - PURPOSE: To compare the primary patency of two structurally different metallic
      stents in an animal model of hemodialysis access grafts. MATERIAL AND METHODS:
      Nineteen synthetic femorofemoral arteriovenous shunts were created in 10 dogs.
      After a 1-month period of maturation (during which one graft thrombosed), stents
      were placed spanning the venous anastomosis. The grafts were divided into two
      treatment groups (Wallstent, n = 6, and Gianturco stent, n = 6) and a control
      group with no stent (n = 6). Fistulograms and pressure measurements were obtained
      at monthly intervals for 6 months or until thrombosis of the graft. RESULTS: Mean
      graft patency in the Wallstent group (112 days +/- 30) was significantly shorter
      than in the control (157 days +/- 32, P < .03) or Gianturco (157 days +/- 32, P <
      .05) groups. Patency in the Gianturco stent group was no different from that in
      the control group. Stenosis due to intimal hyperplasia within the stents appeared
      greater in the Wallstent group but did not achieve statistical significance. One
      Wallstent migration, three Gianturco stents shifts, and two Gianturco stent
      breakages occurred. Histologic examination revealed a necrotizing vasculitis in
      the portion of vein containing the stent in all grafts treated with the Gianturco
      stent but not in any other grafts. CONCLUSION: In an animal model of hemodialysis
      access grafts, the Gianturco stent had longer primary patency than the Wallstent
      when placed across the venous anastomosis. However, stent fractures and focal
      necrotizing inflammation may limit the use of the Gianturco stent in hemodialysis
      access.

PMID- 7647443
TI  - Artificial displacement of kidneys, spleen, and colon by injection of physiologic
      saline and CO2 as an aid to percutaneous procedures: experimental results.
AB  - PURPOSE: To determine whether displacement of the kidneys, spleen, or bowel with
      injection of fluids or CO2 can be used to create a direct and potentially safer
      access route to the retroperitoneum for large-bore needle biopsy or abscess
      drainage. MATERIALS AND METHODS: In cadavers (n = 24), the kidneys were displaced
      laterally by means of computed tomography (CT)-guided paravertebral injection of
      120 mL of physiologic saline solution (n = 18) and 120 cm3 of CO2 (n = 6). The
      spleen (n = 11) and retroperitoneal colon (n = 7) were also displaced with
      saline. Displacement of the organs from the needle tip was measured on CT scans.
      RESULTS: After fluid injection the kidneys shifted 1.47 cm +/- 0.51, the spleen
      shifted 1.14 cm +/- 0.44, and the retroperitoneal colon shifted 1.38 cm +/- 0.37.
      The kidneys obstructed access to the para-aortic space in 17% of cases (four of
      24 cases) and to the entire adrenal gland in 72% (13 of 18 cases) before saline
      injection and in 0% (zero of 24 cases) and 39% (seven of 18 cases), respectively,
      after injection. The result with fluid were significantly better than those with
      CO2 (P < .05). CONCLUSION: Displacement of kidneys, spleen, or retroperitoneal
      colon with a saline injection is effective in gaining an access route for biopsy
      or abscess drainage. Potential for patient discomfort, decrease in target-lesion
      conspicuity, and adverse effects of absorbed fluid in patients with kidney or
      heart disease must be considered with use of this technique in the clinical
      setting.

PMID- 7647444
TI  - Treatment of ureteral obstructions with the Wallstent endoprosthesis: preliminary
      results.
AB  - PURPOSE: To evaluate the efficacy of the Wallstent endoprosthesis in the
      treatment of ureteral strictures. PATIENTS AND METHODS: Wallstents with diameters
      of 10 mm were placed across five malignant and six benign ureteral strictures in
      eight patients. All patients were believed to have poor surgical options, and
      their strictures were being maintained with catheter drainage. Ten lesions
      involved ureteroenteric anastomoses, and one malignancy involved the midureter.
      RESULTS: Three stents (two patients) across malignant disease remained patent
      until the time of patient death (3-5 months); the remaining two stents (one
      patient) became occluded within 1 month. Only one of six stents placed for benign
      disease remained patent at 11 months. All occlusions in benign strictures
      resulted from ingrowth of hyperplastic urothelium and granulation tissue.
      Complete obstruction was usually present only focally within the stent. The
      malignant occlusions were caused by tumor ingrowth and granulation tissue. No
      major complications were directly related to the stents, but two infections
      occurred. CONCLUSION: Wallstent endoprostheses are ineffective in providing long
      term relief in patients with benign ureteroenteric strictures. Further evaluation
      of their role in malignant strictures is needed.

PMID- 7647445
TI  - Treatment of recurrent posterior and bulbar urethral strictures with expandable
      metallic stents.
AB  - PURPOSE: The role of expandable metallic Z stents (non-mesh) in the treatment of
      recurrent posterior and bulbar urethral strictures was evaluated. PATIENTS AND
      METHODS: Seven men with recurrent posterior/bulbar urethral strictures underwent
      balloon angioplasty followed by insertion of two stents in tandem. Retrograde
      urethrography, micturating cystourethrography, and urodynamic evaluation of these
      patients was done initially. RESULTS: Successful dilation and placement of stents
      was possible in all cases. In one patient slight proximal migration of the stent
      occurred; terminal dysuria in this patient necessitated stent extraction. In two
      other patients near total occlusion of the stent by an exuberant fibrous reaction
      occurred and this open urethroplasty in the other. Immediate postprocedure
      urethrography and urodynamic evaluation showed significant improvement. Five
      patients continue to show a satisfactory clinical urodynamic response. The follow
      up period in this patient group ranged from 5 months to 1 year. CONCLUSION: Short
      term response (5 months to 1 year) in patients with posterior/bulbar urethral
      strictures treated with Z stents appears promising. However, the efficacy of the
      procedure on a long-term basis requires further follow-up and evaluation.

PMID- 7647447
TI  - Role of lower extremity US in patients with clinically suspected pulmonary
      embolism.

PMID- 7647448
TI  - Utilization patterns with inferior vena cava filters: surgical versus
      percutaneous placement.
AB  - PURPOSE: To determine whether more inferior vena cava (IVC) filters were used
      after interventional radiologic placement methods became available, and if so,
      whether this increase could be due to expansion of indications. PATIENTS AND
      METHODS: A retrospective analysis of the number of filters placed, the method of
      placement used, the indications for placement, and patient survival was performed
      during the 3 years before and the 3 years after 1989, the first year filters were
      placed percutaneously at the authors' institution. RESULTS: From 1986 through
      1988, 35 filters were all placed by surgeons in the operating room. From 1990
      through 1992, 201 filters were all placed by radiologists in the special
      procedures suite. In the surgery group, 13 of 35 filters (37%) were placed for
      contraindications to anticoagulation therapy, 12 (34%) were placed for
      complications of anticoagulation, and nine (26%) were placed for recurrent
      thromboembolic disease despite anticoagulation. One filter was placed because of
      a free-floating thrombus in the IVC. In the radiology group, 98 of 161 patients
      (60%) underwent placement for contraindications to anticoagulation, 25 (16%)
      experienced complications of anticoagulation, 28 (17%) experienced recurrent
      thromboembolic disease, and nine (6%) had a free-floating thrombus. The 6-month
      survival in patients treated before 1989 was 80% versus 43% after 1989.
      CONCLUSION: At the authors' institution, filters are now placed exclusively by
      interventional radiologists. The overall indications for placement remain
      unchanged. The increase in utilization appears primarily related to more frequent
      placement in severely ill patients who may not experience considerably improved
      survival but may benefit from a substantial reduction in the risk of hemorrhagic
      complications.

PMID- 7647449
TI  - Retrievable IVC filter: preliminary in vitro and in vivo evaluation.
AB  - PURPOSE: To develop an inferior vena cava (IVC) filter that is retrievable even
      after neointimal formation and incorporation into the caval wall. MATERIALS AND
      METHODS: Eight filters were placed percutaneously in the infrarenal IVC of eight
      dogs. Four weeks after placement, percutaneous retrieval of the filters was
      attempted. Vena cavograms were obtained before and immediately after retrieval.
      Three dogs were killed immediately after the retrieval procedure was completed.
      In the other five dogs, follow-up vena cavography was performed 4-14 weeks after
      retrieval, and autopsy was performed. RESULTS: The filters were placed and
      retrieved successfully in all eight dogs. No migration, caval penetration, or
      tilting occurred. The IVCs were completely patent both before and immediately
      after retrieval in all eight dogs. In the three dogs killed immediately after
      retrieval, neointimal hyperplasia was seen around the struts, but there was no
      detachment. Delayed stenosis was not seen in any of the five dogs that were
      followed up, and the inner surface of the caval wall was smooth. CONCLUSION: This
      IVC filter can be easily placed and safely retrieved percutaneously, even after
      neointimal formation.

PMID- 7647446
TI  - Catheter tract hemorrhage during percutaneous biliary intervention: management
      with use of a retained transhepatic guide wire.
AB  - PURPOSE: The authors present their experience in managing freely flowing
      hemorrhage from immature catheter tracts in patients undergoing biliary drainage.
      PATIENTS AND METHODS: Transhepatic guide wires were maintained securely whenever
      catheters were removed from the liver. Six patients among 71 hemorrhaged
      profusely when drains were manipulated within 4 days of initial catheterization.
      Management was attempted with use of the transhepatic guide wires. RESULTS:
      Maneuvers performed over the retained guide wire controlled bleeding in all six
      patients. Reintubation constituted definitive therapy in five patients. A biliary
      portal venous fistula in the remaining patient was treated with thrombin. The
      retained guide wire proved necessary in all cases. CONCLUSION: Hemorrhage from
      immature catheter tracts can be managed, often definitively, with maneuvers
      performed over a retained transhepatic guide wire. Accordingly, a secure
      transhepatic guide wire is essential prior to removal of hepatic catheters and
      should remain in place until the absence of bleeding is established. These
      maneuvers may become increasingly important as courses of biliary catheterization
      become shorter.

PMID- 7647450
TI  - The twist technique: a method to minimize wire prolapse during Bird's Nest filter
      placement.
AB  - PURPOSE: To determine whether a twist technique can help reduce the occurrence of
      fine-wire prolapse proximal to the hooks of the Bird's Nest filter in the
      inferior vena cava. MATERIALS AND METHODS: Abdominal radiographs were
      retrospectively analyzed after placement of filters with no twist (n = 100), with
      two 360 degree twists (n = 55), or with three 360 degree twists (n = 61).
      RESULTS: Prolapse of 5 mm or more was encountered in 32% of cases (32 of 100
      cases) in which no twists were imparted. The average length of prolapse was 2.8
      cm (range, 0.5-5.1 cm). The average length of the filter nest was 9.4 cm (range
      5.1-13.6 cm). Use of two 360 degree twists reduced the rate of prolapse to 9.1%
      (five of 55 cases) (P < .005 vs no twist); the average length of prolapse was 2.8
      cm (range, 0.6-6.4 cm). The average filter-nest length was reduced 7.5 cm (range,
      4.0-13.3 cm). With three 360 degree twists, prolapse occurred in 4.9% of cases
      (three of 61 cases) (P < .005 vs no twist). The average length of prolapse was
      2.6 cm (range, 0.7-4.8 cm). The average filter-nest length was 7.8 cm (range, 3.5
      12.8 cm). The difference in prolapse frequency when two twists were used as
      opposed to three is not statistically significant. CONCLUSION: Application of two
      or three 360 degree twists to the catheter-sheath unit during insertion of the
      Bird's Nest filter produces a statistically significant reduction in the
      occurrence of wire prolapse.

PMID- 7647451
TI  - Effect of a transjugular intrahepatic portosystemic shunt on liver biochemical
      profiles.
AB  - PURPOSE: Transjugular intrahepatic portosystemic shunts (TIPS) have markedly
      simplified the care of patients with refractory variceal bleeding. Follow-up of
      liver biochemical profiles, however, has not been done in a prospective fashion.
      PATIENTS AND METHODS: Twenty-nine patients undergoing TIPS placement for
      refractory variceal bleeding underwent serial laboratory tests and assessment of
      encephalopathy to determine the effect of TIPS. Prothrombin time and aspartate
      aminotransferase, alanine aminotransferase, total bilirubin, alkaline
      phosphatase, serum albumin, serum creatinine, and venous ammonia levels were
      checked prior to the procedure, at the time of discharge, and at 3 weeks, 3
      months, and 6 months following the procedure. RESULTS: There was no statistically
      significant change in any of the obtained laboratory values at up to 6 months of
      follow-up. The change in aspartate aminotransferase level approached but did not
      reach statistical significance at the time of discharge and was thought to be
      secondary to hepatocellular trauma associated with the procedure. New onset of
      encephalopathy occurred in 18.2% of patients and was easily controlled with
      medical therapy. CONCLUSIONS: TIPS does not appear to have a significant effect
      on the liver biochemical profile with short-term follow-up. Hepatic
      encephalopathy does occur, however, in a significant number of patients but is
      easily controlled with medical therapy.

PMID- 7647452
TI  - Technical modification of transjugular intrahepatic portosystemic shunt
      placement: anterior transhepatic approach for the cranially located porta
      hepatis.

PMID- 7647453
TI  - Percutaneous retrieval of two Wallstent endoprostheses from the heart through a
      single jugular sheath.

PMID- 7647454
TI  - Journal of Vascular and Interventional Radiology.

PMID- 7647455
TI  - Guidelines for development and use of transluminally placed endovascular
      prosthetic grafts in the arterial system. Endovascular Graft Committee.

PMID- 7647457
TI  - Endovascular treatment of a posttraumatic bronchial artery pseudoaneurysm.

PMID- 7647456
TI  - Colonic vascular supply from the superior mesenteric artery: an anatomic
      clarification.

PMID- 7647458
TI  - Phylogenetic conservation and physical mapping of members of the H6 homeobox gene
      family.
AB  - Homeobox genes represent a class of transcription factors that play key roles in
      the regulation of embryogenesis and development. Here we report the
      identification of a homeobox-containing gene family that is highly conserved at
      both the nucleotide and amino acid levels in a diverse number of species. These
      species encompass both vertebrate and invertebrate phylogenies, ranging from Homo
      sapiens to Drosophila melanogaster. In humans, at least two homeobox sequences
      from this family were identified representing a previously reported member of
      this family as well as a novel homeobox sequence that we physically mapped to the
      10q25.2-q26.3 region of human Chromosome (Chr) 10. Multiple members of this
      family were also detected in three additional vertebrate species including Equus
      caballus (horse), Gallus gallus (Chicken), and Mus musculus (mouse), whereas only
      single members were detected in Tripneustes gratilla (sea urchin), Petromyzon
      marinus (lamprey), Salmo salar (salmon), Ovis aries (sheep), and D. melanogaster
      (fruit fly).

PMID- 7647460
TI  - A novel partial t haplotype with a brachyury-independent effect on tail
      phenotype.
AB  - The btm (brachyury-interacting tail length modifier) mutation was discovered in
      strain MOL-NIS derived from Japanese wild mice (Mus musculus molossinus) as an
      autosomal recessive mutation. Homozygotes for this mutation show a short tail
      phenotype and, moreover, this mutation causes the tailless character by
      interacting with the T (brachyury) gene on Chromosome (Chr) 17. Our linkage tests
      and RFLP analyses suggest that btm is located within the t complex on Chr 17 and
      represents a new partial t haplotype.

PMID- 7647459
TI  - A high-resolution map of the brown (b, Tyrp1) deletion complex of mouse
      chromosome 4.
AB  - For over 40 years germ-cell mutagenesis experiments have generated many new
      mutations at the brown (b or Tyrp1) locus on mouse Chromosome (Chr) 4. These
      mutations, many of which are deletions, were recovered by the specific-locus
      mutagenesis technique. Previous analysis of a panel of brown deletions, generated
      at Oak Ridge, has enabled both a preliminary molecular and a functional map
      around the locus to be generated. We have used a panel of hybrid DNA from 25 Oak
      Ridge deletions, where the deleted chromosome was heterozygous with a Mus spretus
      chromosome, to map polymorphic markers including microclones, microsatellites,
      and cloned DNA markers. We have generated a fine structure map, based on 25 new
      markers, of an 8.5-cM region surrounding the brown locus. This map will prove
      useful in future mapping studies of this region and in the isolation of the genes
      that lie within it.

PMID- 7647461
TI  - Polymorphism for PCR-analyzed microsatellites between the inbred mouse strains LG
      and SM.
AB  - Using agarose gel electrophoresis, we surveyed four strains of inbred mice
      (AKR/J, C57BL/J, LG/J, and SM/J) for 472 microsatellite loci. Agarose
      electrophoresis proved to be extremely efficient in separating alleles differing
      by six or more base pairs and detected a majority of allelic differences of
      between two and six base pairs. Overall, 64.4% of loci showed polymorphism among
      the four strains, and pairwise comparisons ranged from 42.1% to 48.1%.
      Microsatellite polymorphism for strains LG/J and SM/J has not been previously
      described and was sufficiently high (47.1%) to make these size-divergent strains
      excellent candidates for quantitative trait loci (QTL) analysis of normal growth.

PMID- 7647462
TI  - Ubiquitous expression and imprinting of Snrpn in the mouse.
AB  - Snrpn is known to be abundantly expressed in rodent brain and heart, and in two
      separate studies with neonatal mouse brain it has been shown to be maternally
      imprinted, that is, the maternal allele is normally repressed. We now provide
      evidence on the expression profile and imprinting status of Snrpn throughout
      development. Using RT-PCR, we have established that Snrpn is further expressed at
      low levels in lung, liver, spleen, kidney, skeletal muscle, and gonads. Moreover,
      using mice with only maternal copies of Snrpn (maternal duplication for the
      chromosome region involved and parthenogenotes), we have shown that the gene is
      imprinted in all of these tissues and, generally, from the time the gene is first
      expressed at 7.5 days gestation. In contrast to the findings made with the
      imprinted genes, Igf2, Ins1, and Ins2, there is no evidence of tissue-specific
      imprinting in the embryo with Snrpn. Nor, as found with Igf2 and Igf2r, is there
      evidence of a window of biallelic expression between the germ line imprint and
      the time of gene repression. The absence of Snrpn expression in early embryos
      contrasts with the findings in ES cells.

PMID- 7647464
TI  - The bovine bivariate flow karyotype and peak identification by chromosome
      painting with PCR-generated probes.
AB  - A bovine bivariate flow karyotype has been established from a primary fibroblast
      cell culture carrying a 4;10 Robertsonian translocation. From 27 to 36
      populations could be resolved by flow cytometry although the anticipated number
      was 31. Separation of chromosomal pairs into two populations explains this high
      resolution and confirms the high level of heteromorphism previously observed. We
      used a PARM-PCR (Priming Authorizing Random Mismatches) procedure for the
      production of paint probes from flow-sorted chromosome fractions. These probes
      were used for chromosome identification by fluorescence in situ hybridization
      (FISH) on R-banded metaphase spreads. We present the localization of all the
      bovine chromosome types on the flow karyotype. Twenty-two chromosome types
      including the translocated chromosome were sorted as pure fractions.

PMID- 7647463
TI  - Evolution of a repeat sequence in the parathyroid hormone-related peptide gene in
      primates.
AB  - A polymorphism of the variable number of tandem repeat (VNTR) type is located 97
      bp downstream of exon VI of the parathyroid hormone-related peptide (PTHrP) gene
      in humans. The repeat unit has the general sequence G(TA)nC, where n equals 4-11.
      In order to characterize the evolutionary history of this VNTR, we initially
      tested for its presence in 13 different species representing four main groups of
      living primates. The sequence is present in the human, great apes, and Old World
      monkeys, but not in New World monkeys; and this region failed to PCR amplify in
      the Loris group. Thus, the evolution of the sequence as part of the PTHrP gene
      started at least 25-35 millions years ago, after divergence of the Old World and
      New World monkeys, but before divergence of Old World monkeys and great apes and
      humans. The structural changes occurring during evolution are characterized by a
      relatively high degree of sequence divergence. In general, the tandem repeat
      region tends to be longer and more complex in higher primates with the repeat
      unit motifs all being based on a TA-dinucleotide repeat sequence. Intra-species
      variability of the locus was demonstrated only in humans and gorilla. The
      divergence of the TA-dinucleotide repeat sequence and the variable mutation rates
      observed in different primate species are in contrast to the relative
      conservation of the flanking sequences during primate evolution. This suggests
      that the nature of the TA-dinucleotide repeat sequence, rather than its flanking
      sequences, is responsible for generating variability.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7647465
TI  - CpG island clones for chromosome 11p--a resource for mapping and gene
      identification.
AB  - A NotI end fragment library has been constructed for human Chromosome (Chr) 11p.
      Seventy-two clones were mapped to chromosomal subregions by use of somatic cell
      hybrids. The clones detect 44 different CpG islands, and we have isolated cosmid
      contigs for 36 of them. Extrapolation from the known 11p13 NotI restriction map
      suggests that every second CpG island from 11p containing a Not site is already
      represented in the clone collection. By sequence analysis all of the 11p13 clones
      exhibit typical features of CpG islands, and cross-species hybridization has been
      detected with at least one fragment in most cases. The cosmids serve as valuable
      linking clones for long-range restriction mapping. They also provide excellent
      starting material for transcript isolation procedures to identify genes on
      chromosome 11p associated with developmental anomalies and various tumor types.
      Several transcribed sequences have already been isolated with some of these
      clones.

PMID- 7647466
TI  - An enhanced promoter trap protocol.

PMID- 7647467
TI  - A somatic cell hybrid panel for mouse gene mapping characterized by PCR and FISH.

PMID- 7647469
TI  - The gonadotrophin-releasing hormone receptor maps to sheep chromosome 6 outside
      of the region of the FecB locus.

PMID- 7647468
TI  - Genetic mapping of the RET protooncogene on rat chromosome 4.

PMID- 7647470
TI  - Porcine 5S rRNA genes map to 14q23 revealing syntenic relation to human HSPA6-
      and 7.

PMID- 7647471
TI  - The mouse Gata4 transcription factor maps to chromosome 14.

PMID- 7647472
TI  - Localization of the thyrotropin-releasing hormone gene, Trh, on mouse chromosome
      6.

PMID- 7647473
TI  - Assignment of the gene encoding centrosome-associated protein CCD41 to mouse
      chromosome 2H.

PMID- 7647474
TI  - Assignment of pig alpha 1-antichymotrypsin (AACT or PI2) gene to chromosome
      region 7q23-q26.

PMID- 7647475
TI  - Nutritional considerations and management of the child with human
      immunodeficiency virus infection.
AB  - Early and aggressive nutritional intervention may help to prevent malnutrition in
      HIV-infected children. This in turn may result in slower disease progression and
      improved quality of life. Routine nutritional monitoring and the establishment of
      individualized nutritional goals are necessary for effective of malnutrition and
      the effectiveness of various nutritional therapies will assist in the struggle to
      optimize the clinical care of children with HIV infection.

PMID- 7647476
TI  - Leucine metabolism and body cell mass in cystic fibrosis.
AB  - To further investigate the nature of malnutrition in cystic fibrosis (CF),
      specifically to evaluate the influence of body composition on leucine metabolism
      and determine whether measures used as reference standards alter comparative
      differences in protein metabolism, we measured [13C]leucine kinetics in nine well
      nourished and eight malnourished, height-, FEV1-, and sex-matched CF subjects.
      Body cell mass was measured by total-body potassium (K40) analysis. Leucine
      turnover did not significantly differ between groups in absolute values or when
      corrected for body weight, body height, or surface area. However, malnourished CF
      patients had accelerated leucine turnover based on body cell mass measurements.
      Mean leucine synthesis per unit body cell mass in the malnourished group was 147%
      higher than that of the well-nourished group (p < 0.001). These data indicate
      that altered body composition is an important factor influencing protein
      metabolism in CF and should be considered in future metabolic studies. The
      importance of potentially serious but possibly correctable deficits in body cell
      mass in CF is emphasized.

PMID- 7647477
TI  - Warfarin and reduced central venous thrombosis in home total parenteral nutrition
      patients.
AB  - Central venous thrombosis is a potentially life-threatening complication in
      patients on long-term home total parenteral nutrition (HTPN). Lack of venous
      access due to recurrent thromboses can prevent delivery of life-saving
      nutritional support. The long-term anticoagulation management to prevent
      thromboses in patients with central venous catheters for HTPN has not been well
      established. We have reviewed the role of warfarin in reducing the incidence of
      thromboses and its safety in our HTPN patients. Ninety consecutive HTPN patients
      were studied retrospectively. Twenty-two thromboses occurred during 1312 patient
      mo in 53 HTPN patients on minidose warfarin. A minidose of warfarin is defined as
      1-2 mg and does not prolong the prothrombin time. Seven thromboses occurred over
      619 mo in 18 patients on a therapeutic dose of warfarin (minidose compared to
      therapeutic dose, p > 0.05). A therapeutic dose of warfarin is a dose that
      increases the prothrombin time to 1.2-1.5 times that of control. Twelve patients
      who had 18 thromboses in 323 patient-mo while on minidose warfarin were
      subsequently converted to therapeutic warfarin. The incidence of thromboses
      decreased to 2 in 369 patient-mo (p < 0.005). There were no hemorrhagic
      complications in the minidose warfarin group and four nonfatal hemorrhagic
      complications in the therapeutic dose warfarin group (p > 0.05). A therapeutic
      dose of warfarin is effective in reducing the incidence of thromboses in patients
      who experience central venous thrombosis despite minidose warfarin with a minimal
      increase in hemorrhagic complications.

PMID- 7647478
TI  - A simple technique to reduce ventilator-dependent errors in oxygen consumption
      measurements.
AB  - To evaluate the efficacy of adding a volume reservoir to reduce variability in
      ventilator-induced fluctuation in inspired oxygen concentration (FiO2) and to
      reduce oxygen consumption measurement error, we evaluated two ventilators
      (Puritan-Bennett 7200 and Bear 2) at three inspired oxygen concentrations ranging
      from 35% to 60%. Continuous sampling of oxygen concentration was conducted for
      each ventilator. The maximum variability in oxygen concentration was recorded at
      each minute and oxygen consumption error sensitivity was calculated for both
      ventilators at three different oxygen concentrations, with and without the use of
      a baffled 3-L reservoir placed into the inspiratory circuit between the
      ventilator and test lung. The use of a baffled 3-L reservoir reduced oxygen
      consumption error sensitivity with the Puritan-Bennett 7200 ventilator at all
      three oxygen concentrations (p < 0.01). Similar results were found with the Bear
      2 ventilator except at the highest FiO2, at which oxygen consumption error
      sensitivity was not altered. Use of a baffled volume reservoir can significantly
      reduce ventilator-dependent errors in measuring oxygen consumption via indirect
      calorimetry. However, when the FiO2 is widely variable, the reservoir is not
      helpful in reducing error at higher FiO2 concentrations.

PMID- 7647479
TI  - Glycerol gluconeogenesis in fasting humans.
AB  - The contribution of glycerol to glucose production has been measured in healthy
      volunteers by the simultaneous primed constant infusion of 1-[13C]glycerol and 3
      [3H]glucose and the determination of the rates of appearance (Ra) of glycerol,
      glucose, and glycerol-derived glucose. In the postabsorptive state, glycerol Ra
      was 3.11 +/- 0.44 mumol.kg-1.min-1, of which 36% was converted to glucose,
      accounting for 4.5% of total glucose production. After 62-86 h of starvation,
      glycerol Ra rose to 5.32 +/- 0.58 mumol.kg-1.min-1, and 68% of glycerol was
      converted to glucose. This accounted for 21.6% of total glucose production.
      Glycerol Ra was closely correlated with its conversion and contribution to
      glucose. These findings confirm that the contribution of glycerol to glucose
      production is directly correlated to its release as a consequence of lipolysis
      and support the notion that the central physiological role of accelerated
      lipolysis in fasting is the provision of gluconeogenic precursor.

PMID- 7647480
TI  - A significant methotrexate-glutamine pharmacokinetic interaction.
AB  - Previous studies indicate that glutamine-supplemented diets decrease the
      enterocolitis associated with methotrexate administration. The influence of
      glutamine on the pharmacokinetics of methotrexate and the formation of its major
      hepatic metabolite, 7-hydroxy-methotrexate was examined in 36 adult, female Lewis
      rats. Animals were randomly assigned to receive either a 3% glycine-supplemented
      solid diet (GLY; 25.0% protein; 17.6 kJ/g, or 4.2 kcal/g) or a 3% glutamine
      supplemented solid diet (GLN; 25.0% protein; 17.6 kJ/g, or 4.2 kcal/g) ad libitum
      for 35 days. Animals were separated into two groups (serum methotrexate
      pharmacokinetics, n = 20; or methotrexate renal elimination, n = 16) and given a
      10 mg/kg dose of methotrexate. There was a 25% decrease in mean methotrexate
      total serum clearance in the GLN group compared with the control group (0.63 +/-
      0.09 L.h-1.kg-1 and 0.47 +/- 0.13 L.h-1.kg-1, respectively, p = 0.01). Renal
      methotrexate elimination was decreased by 65%. There was no significant
      difference in methotrexate volume of distribution or half-life between the two
      groups. Glutamine decreases methotrexate systemic clearance, thus exposing the
      host as well as the tumor to greater methotrexate concentrations.

PMID- 7647481
TI  - Metabolic management of hyper- and hypocalcemia.

PMID- 7647482
TI  - Parenteral iron dextran therapy: a review.
AB  - Iron dextran was introduced more than 30 yr ago for the parenteral treatment of
      iron deficiency anemia that is refractory to oral therapy. Iron dextran is a
      preparation of ferric hydroxide complexed with a low molecular weight fraction of
      dextran. Iron deficiency anemia is one of the most common nutritional deficiency
      diseases and occurs worldwide secondary to inadequate dietary iron, usually with
      excessive gastrointestinal blood losses. Repletion of iron stores is often
      complicated by intolerance to oral iron supplementation and may require
      parenteral iron. Parenteral iron can be administered via the intramuscular or
      intravenous route either directly or as an additive to total parenteral
      nutrition. Both routes of administration can cause various side effects and a
      test dose is recommended before therapeutic administration to assess the risk for
      anaphylaxis. Although the efficacy and safety of parenteral iron dextran have
      been convincingly demonstrated, supplementation may be contraindicated in the
      setting of infection.

PMID- 7647483
TI  - Measurement of visceral protein status in assessing protein and energy
      malnutrition: standard of care. Prealbumin in Nutritional Care Consensus Group.

PMID- 7647484
TI  - Colonic fermentation of starch and protein: an end to all resistance?

PMID- 7647485
TI  - Possible mechanism(s) of glutamine-mediated host protection.

PMID- 7647486
TI  - Technical aspects of metabolic measurements.

PMID- 7647487
TI  - Carrots and sticks.

PMID- 7647488
TI  - To keep Jane well ... she needs integrated patient-centered care.

PMID- 7647489
TI  - Simple linear regression and correlation.

PMID- 7647490
TI  - Neuropsychiatric disorders caused by cobalamin deficiency in the absence of
      anemia or macrocytosis. 1988.

PMID- 7647491
TI  - Significance of regurgitation in avian toxicity tests.

PMID- 7647493
TI  - Radiocesium in migratory bird species in Northern Ireland following the Chernobyl
      accident.

PMID- 7647492
TI  - Determination of domoic acid by two different versions of a competitive enzyme
      linked immunosorbent assay (ELISA).

PMID- 7647494
TI  - Lead and mercury levels in raccoons from Macon County, Alabama.

PMID- 7647496
TI  - Contamination of honey with organophosphorus pesticides.

PMID- 7647495
TI  - Dicofol and DDT residues in lizard carcasses and bird eggs from Texas, Florida,
      and California.

PMID- 7647497
TI  - Preliminary study of synergism of acid rain and diflubenzuron.

PMID- 7647498
TI  - Organochlorine and organophosphorus pesticide residues in the water of the Pinios
      River, Greece.

PMID- 7647499
TI  - Cadmium concentrations in human renal cortex tissue (necropsies).

PMID- 7647500
TI  - Monitoring herbicide leaching in sustainable vegetable culture using tension
      lysimeters.

PMID- 7647501
TI  - Chlordane compounds and metabolite residues in termite control workers' blood.

PMID- 7647502
TI  - Detection of sub-clinical lead toxicity in monocasters.

PMID- 7647503
TI  - Risk assessment of organophosphorus pesticide dietary intake for the population
      of the city of Rome (Italy).

PMID- 7647504
TI  - Improvement of acute cadmium toxicity by pretreatment with copper salt.

PMID- 7647505
TI  - Biotoxic effects of copper on ureide metabolism of pigeon pea.

PMID- 7647506
TI  - Role of citrate as a complexing ligand which permits enzymically-mediated uranyl
      ion bioaccumulation.

PMID- 7647507
TI  - Quantitative alterations in the liver and adrenal gland in pregnant rats induced
      by Pyralene 3000.

PMID- 7647508
TI  - Inhibitory effects on degradation of diesel oil in soil-microcosms by a
      commercial bioaugmentation product.

PMID- 7647509
TI  - Comparative analyses of contaminant levels in bottom feeding and predatory fish
      using the National Contaminant Biomonitoring Program data.

PMID- 7647510
TI  - Differential response of marine diatoms to solvents.

PMID- 7647512
TI  - AHNA certificate program in holistic nursing courses; AHNA certificate program in
      healing touch courses.

PMID- 7647511
TI  - Pollution chronology of Lake Valencia, Venezuela.

PMID- 7647513
TI  - Holistic medicine in action: the treatment of chronic disease.

PMID- 7647514
TI  - IXth World Congress on In Vitro Fertilization and Alternate Assisted
      Reproduction. Vienna, Austria, April 3-7, 1995. Abstracts.

PMID- 7647515
TI  - A simple and effective method for the removal of trace metal cations from a
      mammalian culture medium supplemented with 10% fetal calf serum.
AB  - Direct batch addition of sterile Chelex ion-exchange resin to Dubecco's modified
      Eagle's medium supplemented with 10% fetal calf serum with gentle stirring
      removed a very wide variety of trace metal ions from the medium to varying
      extents dependent upon Chelex content (between 0.01 and 4% w/v), exposure time
      (between 5 min and 10 days) and temperature (4, 25 and 37 degrees C). Prolonged
      treatment (10 days) with 4% w/v Chelex at 4 degrees C reduced the concentration
      of zinc, strontium, aluminum, copper, manganese, nickel and chromium from 100 to
      2.7, 12.1, 7.7, 22.6, 13.0, 14.7 and 53.3% of their original concentrations,
      respectively. Re-supplementation of the metal depleted medium with a defined
      cocktail of metals restored the growth potential of the medium which was then
      capable of supporting growth over at least three subcultures without a decrease
      in fibroblast cell yield, demonstrating its suitability in cell culture studies
      on trace metal ions.

PMID- 7647516
TI  - Energetic basis of cadmium toxicity in Staphylococcus aureus.
AB  - In washed cells of cadmium-sensitive Staphylococcus aureus 17810S oxidizing
      glutamate, initial Cd2+ influx via the Mn2+ porter down membrane potential (delta
      psi) was fast due to involvement of energy generated by two proton pumps--the
      respiratory chain and the ATP synthetase complex working in the hydrolytic
      direction. Such an unusual energy drain for rapid initial Cd2+ influx is
      suggested to be due to a series of toxic events elicited by Cd2+ accumulation
      down delta psi generated via the redox proton pump: (i) strong inhibition of
      glutamate oxidation accompanied by a decrease of electrochemical proton gradient
      (delta mu H+) formation via the respiratory chain, (ii) automatic reversal of ATP
      synthetase from biosynthetic to hydrolytic mode, which was monitored by a
      decrease of delta mu (H+)-dependent ATP synthesis, (iii) acceleration of the
      initial Cd2+ influx down delta psi generated by the reversed ATP synthetase, the
      alternative proton pump hydrolyzing endogenous ATP. The primary, cadmium
      sensitive targets in strain 17810S seem to be dithiols located in the cytoplasmic
      glutamate oxidizing system, prior to the membrane-embedded NADH oxidation system.
      Inhibition by Cd2+ of delta mu (H+)-dependent ATP synthesis and of pH gradient
      (delta pH)-linked [14C]glutamate transport is a secondary effect due to cadmium
      mediated inhibition of delta mu H+ generation at the cytoplasmic level. In washed
      cells of cadmium-resistant S. aureus 17810R oxidizing glutamate, Cd2+
      accumulation was prevented due to activity of the plasmid-coded Cd2+ efflux
      system. Consequently, delta mu (H+)-producing and -requiring processes were not
      affected by Cd2+.

PMID- 7647517
TI  - Increased urinary zinc excretion in cancer patients is linked to immune
      activation and renal tubular cell dysfunction.
AB  - Urinary zinc excretion is known to be increased in cancer patients, but the
      pathogenesis of this phenomenon remains uncertain. Both skeletal muscle
      catabolism and renal tubular cell dysfunction have been proposed to explain this
      observation. We have investigated urinary zinc and N-acetyl-beta-D
      glucosaminidase (NAG), an indicator of renal tubular cell dysfunction, as well as
      serum neopterin, an index of systemic immune activation, in 22 patients with
      cancer and seven controls. Both serum neopterin and urinary zinc were
      significantly elevated in cancer patients (15.8 +/- 12.7 versus 7.3 +/- 2.3 nmol
      l-1 and 1.77 +/- 0.80 versus 1.21 +/- 0.41 mmol mol-1 creatinine, P < 0.02 and P
      < 0.05, respectively), while NAG was similar in cancer patients and the controls
      (13.58 +/- 13.80 versus 13.68 +/- 12.19 mu kat mol-1 creatinine). A significant
      correlation was observed between serum neopterin and urine zinc (rs = 0.5119, P <
      0.02), serum neopterin and urine NAG (rs = 0.6761, P < 0.002), and urinary zinc
      and NAG (rs = 0.6348, P < 0.002). In conclusion, the present data indicate a link
      between urinary zinc excretion and immune activation as well as renal tubular
      cell dysfunction. In addition, renal tubular cell dysfunction appears to be
      linked to immune activation.

PMID- 7647518
TI  - The mobile ferrous iron pool in Escherichia coli is bound to a phosphorylated
      sugar derivative.
AB  - Based on in vivo Mossbauer spectroscopy it has previously been demonstrated that
      the intracellular iron pool of Escherichia coli, grown in iron deficient media
      supplemented with siderophores as the sole iron source, is dominated by a single
      Fe2+ and a single Fe3+ species. We have isolated the ferrous ion species and have
      purified it employing native column PAGE, chromatography and ultrafiltration. The
      purified compound displays an Mapp of 2.2 kDa and an extremely low isoelectric
      point (pI) of 1.05. It is shown that this ferrous ion binding compound is neither
      a protein nor a nucleotide, rather it is composed mainly of phosphorylated sugar
      derivatives. This compound binds approximately 40% of the cytoplasmic iron.
      Therefore it is proposed that this oligomeric ferrous carbohydrate phosphate
      represents the long sought after mobile, low molecular mass iron pool.

PMID- 7647519
TI  - Bioavailability of lead from various milk diets studied in a suckling rat model.
AB  - The bioavailability of lead from various milk diets was studied in 14 day old
      suckling rats. Human milk, infant formula, cow's milk, rat milk and deionized
      water labeled with 203Pb were given to rat pups by gastric intubation. Animals
      were killed after 2 or 6 h and the radioactivity in the tissues was measured. At
      2 h after administration the lead bioavailability, defined as lead uptake in the
      body, excluding the gastrointestinal tract, was 47% from water, 42% from human
      milk, 40% from infant formula, 31% from cow's milk and 11% from rat milk. After 6
      h the bioavailability of lead was about 50% from water and human milk, 45% from
      infant formula and cow's milk, and 36% from rat milk. The blood lead levels in
      the pups reflected the total body uptake and were also correlated to the brain
      lead levels. Thus, rat pups given lead in human milk had approximately twice as
      high lead levels in blood and brain than pups given lead in rat milk. The
      intestinal absorption of lead was dependent on the milk diet given to the
      sucklings. In duodenum, the highest uptake of lead was found in rats given water
      or human milk, whereas in rats given rat or cow's milk the highest uptake of lead
      was found in ileum. The distribution of lead in cream, whey and casein fractions
      of the milk diets after in vitro labeling with 203Pb was also studied. The casein
      fraction in cow's and rat milk contained 90-96% of the total amount of lead in
      the diet.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7647520
TI  - Prolonged incubation with low concentrations of mercury alters energy transfer
      and chlorophyll (Chl) a protein complexes in Synechococcus 6301: changes in Chl a
      absorption and emission characteristics and loss of the F695 emission band.
AB  - Synechococcus PCC 6301 cells grown in the presence of low sublethal levels of
      (about 2 microM) mercury induced alterations in chlorophyll (Chl) a absorption
      without significant alterations in phycocyanin. Chl a fluorescence emission in
      Hg(2+)-raised cells showed a large (about 18 nm) blue shift in the peak emission.
      No major spectral changes in phycobilisome (PBsome) emission characteristic were
      noticed, indicating major structural alterations in Chl-protein complexes by
      incubation with Hg2+ ions. Low temperature (77K) emission spectra of cells grown
      in the presence of Hg2+ showed a loss of the characteristic Chl a emission band
      at 695 nm (F695), which is known to be linked to photosystem II photochemistry
      and to originate from the Chl a of core antenna polypeptide CP 47 of photosystem
      II. The SDS-PAGE polypeptide profile of thylakoids indicates a loss of a
      polypeptide(s) with a molecular mass between 40 and 60 kDa by Hg2+ incubation of
      cells. Our results suggest that prolonged incubation of Synechococcus 6301 cells
      with low concentrations of Hg2+ affects the Chl a spectral properties and the
      structure of Chl-protein complexes.

PMID- 7647521
TI  - Lead exposure in Saudi Arabia and its relationship to smoking.
AB  - Lead was determined in whole blood samples obtained from 202 Saudi male
      volunteers. The influence of smoking on lead exposure was investigated. Blood
      lead was significantly higher in current smokers than in non-smokers and previous
      smokers (P < 0.05). The distribution of blood lead data in the screened subjects
      suggested the existence of two mixed populations and a cut-off of 12 micrograms
      dl-1 was found where the two populations separate. Of the exposed population, 80%
      with blood lead concentrations above 12 micrograms dl-1 were smokers.

PMID- 7647523
TI  - [Effects of dihydroxyacetophenone on pulmonary hemodynamics and plasma ANP as
      well as cAMP/cGMP level in patients with chronic obstructive pulmonary disease].
AB  - In order to study the effect of dihydroxyacetophenone (DHAP) on pulmonary
      hemodynamics and its relationship to plasma ANP as well as cAMP/cGMP level in
      chronic obstructive pulmonary disease (COPD), 11 COPD patients were examined with
      the right heart catheterisation, and the plasma ANP and cAMP/cGMP were measured
      with radioimmunoassay at the same time. The results showed that intravenous given
      DHAP 640 mg could decrease mean pulmonary arterial pressure, pulmonary vascular
      resistance and systemic vascular resistance (P < 0.05), but increase the cardiac
      output from 4.10 +/- 1.08 L/min to 5.13 +/- 1.19 L/min (P > 0.05) and not affect
      systemic arterial pressure (P > 0.05) as well as blood gas analysis; it also
      reduce the plasma ANP and cGMP level from 0.73 +/- 0.42 pg/ml to 0.41 +/- 0.33
      pg/ml (P < 0.01) and from 9.82 +/- 5.75 pm/ml to 8.01 +/- 4.80 pm/ml (P < 0.05)
      respectively, but did not affect the plasma cAMP level (P > 0.05). It is
      suggested that DHAP may relax pulmonary vessels by regulating the ratio of cAMP
      to cGMP, and the lowering of plasma ANP level might be a secondary reaction. So
      we consider that DHAP is a fast-acting, safe and potential drug in treating
      pulmonary arterial hypertension by COPD.

PMID- 7647522
TI  - Age-related alterations in cell division and cell cycle kinetics in control and
      trimethyltin-treated lymphocytes of human individuals.
AB  - Trimethyltin chloride induced age-related suppression of cell division and cell
      cycle kinetics in human peripheral blood lymphocytes cultured in RPMI 1640
      culture medium supplemented with human AB serum, phytohemagglutinin and
      bromodeoxyuridine. A high frequency of M1 (first metaphase) cells was seen in
      cultures treated with a high dose (C1 = 1.0 microgram per culture) and in
      lymphocytes from donors in the age range 40-70 years. The delay in cell division
      and cell cycle kinetics may indicate a longer duration in DNA synthesis induced
      by trimethyltin chloride in aged lymphocytes.

PMID- 7647524
TI  - [Effect of tetramethylhyrazine on proliferation of human fetal mesangial cells].
AB  - Tetramethylhyrazine (TMP) 0.6 and 1.2 mmol were added to human fetal mesangial
      cell (MC) cultures for 6 days, and the amounts of MC (cells/ml) were 37580 +/-
      3475 and 27350 +/- 3418 respectively, significantly lower than that 71850 +/-
      5108 in control (P < 0.05). The 3H-TdR incorporation by the MC with corresponding
      TMP were 1017 +/- 201 and 583 +/- 271, also significantly lower, than that 3575
      +/- 306 in control (P < 0.01). After adding the TMP (1 mmol) to the cultures, the
      IL-6 bioactivity were 2118 +/- 215 that were markedly lower than those in
      controls (4128 +/- 351, P < 0.01). It revealed that the TMP inhibited the growth
      of MC and the mechanism of its inhibition might be due to that TMP could reduce
      the IL-6.

PMID- 7647526
TI  - [Effects of Astragalus membranaceus on left ventricular function and oxygen free
      radical in acute myocardial infarction patients and mechanism of its cardiotonic
      action].
AB  - Dynamic observations for 4 weeks were made on left ventricular function and
      oxygen free radical (OFR) in 43 patients first suffering from acute myocardial
      infarction and hospitalized in Coronary Care Unit with an attack less than 36
      hours. The results showed that the Astragalus membranaceus (AM) could strengthen
      the left ventricular function and had an effect of anti-OFR. After administration
      of AM, the ratio of pre-ejection period/left ventricular ejection time (PEP/LVET)
      was decreased, the superoxide dismutase (SOD) activity of red blood cell was
      increased, and the lipid peroxidation (LPO) content of plasma was reduced. There
      was a significant difference between the AM group and the control group in the
      parameters above-mentioned. The study demonstrated that the PEP/LVET ratio was
      closely correlated with the SOD and LPO. It suggested that the anti-OFR effect of
      AM was one of the mechanisms of its cardiotonic action.

PMID- 7647525
TI  - [Good regulation of acupuncture in simple obesity patients with stomach-intestine
      excessive heat type].
AB  - In order to investigate the regulatory effect of acupuncture on obesity patients
      with the Stomach-Intestine Excessive Heat Type, the pre-acupunctural and post
      acupunctural obesity index and biochemical indices of 718 patients with simple
      obesity was observed. It was showed that the marked weight loss effects was
      achieved in the cases by acupuncture, while the biochemical indices improved. It
      suggests that acupuncture had a good regulatory effect on the function of nerve,
      endocrine, digestion and energy metabolism.

PMID- 7647527
TI  - [Effect of fu-fang si-shen yin on cellular immunity in patients with viral
      myocarditis].
AB  - In order to study the effect of the Fu-Fang Si-Shen Yin (FFSSY) on cellular
      immunity, the natural killer (NK) cell activity of 60 patients with viral
      myocarditis, while the lymphocyte subsets consisted of OKT3, OKT4, OKT8,
      OKT4/OKT8 of other 20 patients were determined. The pretreatmental results were
      25.25 +/- 0.46%, 59.11 +/- 8.72%, 30.72 +/- 6.94%, 29.72 +/- 5.35% and 1.04 +/-
      0.24 respectively, which were significantly lower than that of the normal value
      (P < 0.01) except OKT8 However, after the treatment with FFSSY, NK cell activity
      and OKT3, OKT4, OKT4/OKT8 were elevated to 30.96 +/- 10.13% (P < 0.05), 62.33 +/-
      7.78% (P < 0.05), 33.67 +/- 5.50% (P < 0.05) and 1.14 +/- 0.20 (P < 0.01)
      respectively. The Syndrome Differentiation of TCM indicated that NK cell activity
      decreased obviously in the Qi-Yin-Deficiency group, while T lymphocyte subsets
      changed significantly in the Qi-Deficiency group. There existed negative
      correlation between NK cell activity and OKT4/OKT8 (r = -0.60, P < 0.05). The
      patients with high NK cell activity in the early stage could have a favourable
      prognosis, while unfavourable with low NK cell activity.

PMID- 7647528
TI  - [Effects of 24 Chinese medicinal herbs on nucleic acid, protein and cell cycle of
      human lung adenocarcinoma cell].
AB  - Using flow cytometry the authors analysed the effect of 24 Chinese medicinal
      herbs (CMH) in compound recipe on proliferation index (PI), DNA index, protein
      index and ratio of various phases in cell cycle of human lung adenocarcinoma cell
      (SPC-A-1), The PI were more than 20%, in 4 CMH, while 3 CMH such as Gynostemma
      pentaphyllum, Glehnia littoralis, Panax Ginseng, could strengthen the body
      resistance. That suggested using CMH of strengthening body resistance not only
      served as conventional tonice but also as tumor cell inhibitor. Meanwhile the
      action point of 24 CMH on cell cycle were different. Therefore according to these
      results a new recombined Chinese recipe would be more effectively used for
      clinical practice.

PMID- 7647529
TI  - [Effects of leech and ground beetle powder on hemorheology and blood lipid of
      ischemic stroke].
AB  - In order to improve blood supply for the brain, restore the functions of the
      cerebral cells and the limbs, and increas the curative rate, the leech (Hirudo
      nipponica and ground beetle Eupolyphage sinensis), powder (LGBP) to the patients
      according to the principle of promoting the blood circulation to remove the
      stasis was administered, and the clinical observation and experimental study was
      conducted. Its effects were compared with those of Western medicines. The results
      showed that after medication of LGBP, the blood flow of brain significantly
      increased, the hypoxia was improved, blood viscosity and blood lipid were lowered
      and thrombosis was inhibited in vitro or in vivo. No toxic side-effects caused by
      LGBP was found.

PMID- 7647530
TI  - [Observation on treatment of mailuoning injection for 46 pregnancy induced
      hypertension patients].
AB  - In order to observe the effect of treatment of Mailuoning Injection (MI) for
      pregnancy induced hypertension (PIH), 46 PIH patients in treated group were
      treated with intravenous dripping of MI and 40 patients in control group were
      treated with intravenous dripping of 25% magnesium sulfas. The result showed: The
      headache and edema ameliorated significantly in treated group in comparison with
      control (P < 0.05). Both methods could decrease the levels of mean arterial
      pressure, but the former's lowering arterial pressure was better than that of
      latter's (P < 0.05-0.01). The improvements of hemorheology in both groups after
      treatment were found, but the decrease of hematocrit was more significant in
      treated group (P < 0.05). No difference was found in albuminuria, delivery
      pattern, postpartum bleeding and neonatal Apgar Score between the two groups. The
      result suggested that the MI could prevent the progress of pathological process
      of the PIH, and relieve the systemic arteriolospasm, improve the
      microcirculation, change the hypercoagulability of the patients' blood and
      increase the blood flow in the patient of PIH.

PMID- 7647531
TI  - [Observation of cardiac function, hemorheology and lingual microcirculation of
      leukemic patients].
AB  - The cardiac function, hemorheology and the lingual microcirculation of the 62
      leukemic patients were investigated. The results showed that their left cardiac
      function was markedly damaged, and the blood specific viscosity and hematocrit
      lowered, the time of RBC electrophoresis extended, the ESR and the K value of ESR
      equation was increased, which suggested the blood agglutination was enhanced. The
      lingual microcirculation obviously displayed reducing the number of papilla
      fungiformis, of intrapapillar plexus of microvessel as well as vessel loops, it
      also revealed the increasing of the abnormal form of microvessel and of the
      dilating vessel loops. The colour of the blood flow showed pink and dark red, the
      condition around vessel loops showed exudation and bleeding in several cases.

PMID- 7647532
TI  - [Effect of ming-men mixture on corticosterone-rats' neuro-endocrino-immunological
      network].
AB  - The hypothalamus-pituitary adrenal-thymus(HPAT) axis is an important form of the
      neuroendocrino-immunological network (NEIN). To study the essential link between
      Ming-Men, Kidney and the NEIN, the corticosterone (CORT) injected rats was used.
      The CORT The CORT caused HPAT axis inhibiting model was established and then the
      regulation of Ming-Men mixture (MMM) was observed. The results showed that the
      number of corticotropin-releasing factor (CRF) positive neurones in hypothalamic
      paraventricular nucleus, CRF positive neurofibril in in median eminence, anterior
      pituitary ACTH positive secretory cells decreased markedly in the CORT inhibited
      rats and the immunohistochemical ABC staining became lighter than the control. We
      also observed that there was atrophy in adrenal, especially fasculate zone became
      thinner compared with the control. The thymus atrophied, the number of
      lymphocytes and thymic corpuscles decreased obviously. The content of ACTH and
      CORT in plasma decreased, the proliferative reaction of lymphocytes, interleukin
      2 and the inductive ability of gamma-IFN reduced. After the MMM was instilled
      into stomach in experimental group, it was foiund that MMM could improve the
      inhibition on HPAT axis caused by CORT significantly, P < 0.01. It suggested that
      MMM possibly was an effective and ideal prescription which could regulate the
      HPAT axis.

PMID- 7647534
TI  - [Comparison of effect of Astragalus membranaceus and huoxuefang on thromboxane,
      prostacyclin and adenosine cyclic monophosphate in cerebral reperfusion injury in
      rabbits].
AB  - The cerebral ischemia rabbit model was made by using the occlusion of four
      vessels. The results showed that TXB2 and cAMP contents in brain tissues and the
      latter in plasma markedly increased (P < 0.05, P < 0.01), the 6-keto-PGF1 alpha
      in brain tissues significantly lowered (P < 0.05) in ischemia formed 30 minutes
      and 45 minutes after reperfusion. After intravenous injection of Astragalus
      membranaceus (AM) extracts (3.3 g/kg), Huoxuefang (HXFO and Yiqi Houxue Fang
      (YQHXF) consisted of AM and HXF before ischemia, the marked increase of TXB2
      contents after reperfusion was inhibited (P < 0.05) and the 6-keto-PGF1 alpha in
      brain tissues after reperfusion were increased (P < 0.01) in HXF and YQHXF group,
      which change the AM extracts didn't have (P < 0.05). HXF could markedly inhibit
      the increase of cAMP in brain tissues after reperfusion P < 0.05), while the AM
      extracts and YQHXF couldn't (P > 0.05). All above-mentioned suggested that the
      above-mentioned suggested that the balance disorder of TXA2/PGI2 in brain tissues
      might participate in the occurrence of cerebral reperfusion injury and YQHXF
      might act against this injury by means of improving the balance of TXA2/PGI2 in
      brain tissues, which was mainly released by HX drugs of it.

PMID- 7647533
TI  - [Effect of shen mai injection and its combinations on blood gas and hemodynamics
      of rats exposed to chronic hypoxia].
AB  - Shen Mai Injection (SMI) consisted of Panax ginseng and Ophiopogon japonica might
      promote the myocardial and diaphragmatic muscle contraction. The effect of SMI
      and its combinations were examined on the blood gas and hemodynamics of rats
      exposed to chronic hypoxia. SMI reduced significantly the pulmonary vascular
      resistance (PVR, P < 0.001), systemic vascular resistance (SVR, P < 0.001) and
      increased cardiac output (CO, P < 0.001), which effect was superior to the
      Dobutamine. If SMI was combined with Ligustrazine etc, better effect on blood gas
      and hemodynamics appeared than that of combined with other drugs. These combined
      group also presented more selective on pulmonary circulation. The results
      suggested that SMI and its combined with Ligustrazine could relieve the pulmonary
      hypertension and diaphragmatic fatigue.

PMID- 7647535
TI  - [Experimental study on cell cycle in rabbits' aortic smooth muscle cell culture
      in vitro with tongmai jiangzhi liquor].
AB  - The effects of Tongmai Jiangzhi Liquor (TMJZL) on the cell cycle kinetics in
      smooth muscle cell (SMCO of rabbits' midlayer of aortic wall was observed. It was
      showed that TMJZL could extend the time of cell culture, lower the percentage of
      SMC in G0/G1 phase and elevate the percentage of SMC in S phase gradually. The
      higher the concentration, the stronger the effect. The experiment showed that
      TMJZL had a marked inhibition of SMC of rabbits' midlayer of aortic wall cultured
      in vitro.

PMID- 7647536
TI  - [Recent progress in the study of free radicals in traditional Chinese medicine].

PMID- 7647537
TI  - [Progress in the study of bronchial asthma with traditional Chinese medicine].

PMID- 7647538
TI  - [Opinions on current international development of medicinal plants].

PMID- 7647539
TI  - [Effect of Epimedium sagittatum on quality of life and cellular immunity in
      patients of hemodialysis maintenance].
AB  - Our previous study had demonstrated that Chinese medicine Epimedium Sagittatum
      (ES) exerted immuno-enhancing effect on the animal model of chronic renal
      insufficiency. In present study, we investigated the therapeutic effect of ES on
      patients of hemodialysis maintenance. 22 cases of regular hemodialytic patients
      were treated with ES in the form of decoction. 12 patients with hemodialysis were
      served as controls. It was found that ES had sexual potentiation effect and
      improved the quality of life in the patients of chronic renal failure with
      regular hemodialysis. Interleukin 2 (IL-2) activity of peripheral blood monocytes
      (PBMC) stimulated by PHA was increased significantly in the patients treated with
      ES. It was suggested that Chinese medicine ES had therapeutic effect on sexual
      disorder and immunologic inadequacy in the patients of chronic renal failure
      undergoing hemodialysis.

PMID- 7647540
TI  - [Clinical study on treatment of male infertility with shengjing pill].
AB  - 202 cases of male infertility were treated with Shengjing Pill. After treatment,
      quantity and quality of sperm were significantly improved (P < 0.001), levels of
      follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone (T)
      were enhanced to normal in 96 patients (P < 0.001), levels of anti-sperm-antibody
      was reduced to normal in 45 cases (P < 0.001), of 148 follow-ups. Their 116
      spouses became pregnant and have borne 108 well-developed babies.

PMID- 7647541
TI  - [Clinical and experimental study on composite wuzi dihuang liquor in treating
      male infertility].
AB  - Composite Wuzi Dihuang Liquor (CWDL) in treating male infertility was used. The
      results showed that the effective rate was 84%. CWDL is indicated in mild and
      medium idiopathic oligozoospermia. There was some effect in the male infertility
      which was complicated by prostatitis, varicocele, antisperm antibody positive
      patients, but was ineffective in severe oligozoospermia, azoospermia, tesicular
      volume 15ml, endocrinologic and chromatic abnormality. Experimental study
      revealed that the drug could significantly increase the percentage of
      reproductivity in mice and could directly safeguard the sperm of male infertility
      patients.

PMID- 7647542
TI  - [Clinical study on effects of buyang huanwu decoction on coronary heart disease].
AB  - 102 cases of coronary heart disease (CHD) were divided randomly into two groups,
      70 cases were given orally the Buyang Huanwu Decoction (BYHWD) for 15 days and
      were compared with 32 control patients. The effect of BYHWD in treating angina
      pectoris and the change of EKG before and after the treatment were observed. The
      results were as follows: in BYHWD group the serum level of lipoperoxide (LPO),
      apolipoprotein (apo) B100, LPO/SOD (superoxide dismutase) and apo B100/apo A1
      were lowered remarkably, the serum of SOD and apo A1 were elevated significantly
      (P < 0.01) comparing with the control group. The total effective rate of treating
      angina pectoris was 91.4%. But the difference was insignificant compared with the
      control group (P < 0.05). The EKG improvement rate was 85.7% in BYHWD group, the
      difference was very significant comparing with control group (P < 0.05). The
      results indicated that BYHWD had a good effect on removing the oxygen free
      radicals, reducing the injury of LPO and regulating the apolipoprotein metabolism
      in the patients with CHD. Therefore BYHWD is an effective TCM remedy for CHD.

PMID- 7647543
TI  - [Study on therapeutic mechanism of xi lei powder for peptic ulcer].
AB  - We studied 128 patients with active peptic ulcer diagnosed by gastro-endoscopy
      four weeks after treatment with Xi Lei powder, PGE2 levels in both serum and
      gastro-duodenal mucosa were significantly higher than that before the treatment,
      the difference was significant (P < 0.01). The rate of negative conversion of
      Helicobacter pylori (HP) showed in 63.3% of cases. The distributed density of HP
      significantly reduced, the difference was significant (P < 0.01). These results
      indicated that Xi Lei powder could heal ulcer probably owing to the increasing of
      the PGE2 level in gastroduodenal mucosa, it inhibited the growth and reproduction
      of HP, and eliminated the HP, but did not inhibit the secretion of gastric acid
      and release the gastrin.

PMID- 7647544
TI  - [Significance on deformability of red blood cells and peripheral microcirculation
      analysis in "disease" and "syndrome" diagnosis].
AB  - Following the principle of Syndrome study in TCM, parallel control groups were
      set up according to "the same disease with different Syndromes" and "different
      disease with the same Syndrome", the significance on deformability of red blood
      cells and peripheral microcirculation analysis in "disease" and "Syndrome"
      diagnosis were explored. Results showed: the both parameters were not
      characteristics of "disease" diagnosis, but were characteristics of "Syndrome"
      diagnosis. It suggested that: both "disease" and "Syndrome" reflected
      pathophysiological state of human body in disorder, and "Syndrome" is a highly
      condensed expression of this status.

PMID- 7647545
TI  - [Effect of bushen shengxue recipe on EPO gene expression of chronic renal
      insufficiency anemia in rats].
AB  - The rats were fed with adenine to establish the chronic renal insufficiency
      anemia model, and the relationship between renal functional impairment and
      reticulocytes, hemoglobin and erythropoietin (EPO) synthesis was observed to
      explore the mechanism of Bushen Shengxue drugs in improving the hemopoietic
      function. The results showed that the Bushen Shengxue drugs could significantly
      lower the serum creatinine and blood urea nitrogen of renal insufficiency rats,
      and through the promotion of EPO gene expression, the animals' anemic status was
      improved.

PMID- 7647546
TI  - [Experimental study on anti-duck hepatitis B viral effect of Phyllanthus urinaria
      of different areas and combined therapy with other drugs].
AB  - The duck hepatitis B virus model was treated with phyllanthus urinaria of
      different area and combined with Sophora flavesceus as well as ciprofloxacin once
      a day for one month, the results indicated: Guangxi and Yunnan Phyllanthus could
      lower the serum DHBV DNA significantly (P < 0.05), but Chongqing Phyllanthus
      couldn't. And the amount of serum DHBV DNA rose a week after stopping of Yunnan
      Phyllanthus. The antiviral effect of Guangxi Phyllanthus combined with
      ciprofloxacin seems to be strengthened (P < 0.05).

PMID- 7647547
TI  - [Pathologic studies on preventive and therapeutic effects of the formic mixture
      on experimental silicosis].
AB  - In order to investigate the preventive and therapeutic effects of formic mixture
      on experimental silicosis, 96 Wistar rats were divided randomly into three
      groups, 1st group was taken as preventive administration (Two days before
      exposure to dust), 2nd group-therapeutic administration (one month after exposure
      to dust) and 3rd control group-model of silicosis. All above-mentioned animals
      were instilled intratracheally with standard quartz dust. At 1st, 3rd, 6th and
      12th month after instillation of dust, rats from each group were sacrificed and
      pathohistologic studies were performed on their lung tissue. The results showed
      that the progressive degree of silicotic fibrosis in various groups were greatly
      different, i. e. 3rd group was severest, 2nd group medium, and 1st group was
      mildest. Either the differences of grade or quantity of fibrosis in lung tissue
      was significant between 1st and 3rd group, P < 0.01. The difference of the grade
      of fibrosis between 2nd and 3rd group was also significant, P < 0.05, but that
      between 1st and 2nd group was insignificant. The results demonstrated that
      administration of formic mixture, in particular, preventive administration, could
      inhibit greatly the process of silicotic fibrosis, and provided a basis for
      clinical application of this drug.

PMID- 7647548
TI  - [Effect of Tibetan compound prescription on cardiac haemodynamics in experimental
      myocardial ischemia in dogs].
AB  - 35 healthy and hybrid dogs were divided into the control group (5 dogs), ischemic
      group (15 dogs) and medicated group (15 dogs). The myocardial ischemia model was
      produced by ligating the left coronary artery between the branch 2 and 3 among
      the anterior descending branches. The effect of the herbs on the experimental
      myocardial ischemia was observed by measuring the Mean Artery Pressure (MAP), the
      Left Ventricular End Diastolic Pressure (LVEDP), the Heart Rate (HR), the Cardiac
      Output (CO) and the Cardiac Index (CI) etc. The results showed that the LVEDP was
      significantly increased and the MAP, the CO and the CI were lowered during the
      period of myocardial ischemia, which indicated the disorder of cardiac
      heaemodynamics after the myocardial ischemia, By taking the medicine through the
      duodenum in the medicated group, the CO was obviously increased during the period
      of myocardial ischemia and also the CI was elevated prominently. The
      investigation indicated that the medicine could reinforce the cardiac pump
      function and adjust the disorder of cardiac haemodynamics resulted from
      myocardial ischemia.

PMID- 7647550
TI  - [Current status of pharmacological study on Cordyceps sinensis and Cordyceps
      hyphae].

PMID- 7647549
TI  - [Physiological and clinical significance of erythrocyte deformability].

PMID- 7647551
TI  - Influence of the glycosidic torsion angle on 13C and 15N shifts in guanosine
      nucleotides: investigations of G-tetrad models with alternating syn and anti
      bases.
AB  - The effect of the glycosidic torsion angle on 13C and 15N shifts of the sugar and
      base moieties of guanosine nucleotides was investigated by comparing the sites in
      two model G-tetrad oligodeoxynucleotides that contain guanosine residues
      alternately with syn and anti bases. The sugar puckering has been shown to be C2'
      endo for both cases. It was observed that, for the instances with syn bases, the
      C1' through C4' carbons showed shifts that may be distinguished from those
      normally found in B-DNA-like structures. C1', C3' and C4' moved to lower field,
      while C2' moved to higher field. Effects of the change in glycosidic torsion
      angle were also seen in the shifts of base carbons and nitrogens in the five
      membered ring portion of the base. Characterization of the shift variation
      associated with this conformational change may be useful in developing the use of
      13C shifts as a tool in conformational analysis of oligonucleotides.

PMID- 7647552
TI  - High-level 2H/13C/15N labeling of proteins for NMR studies.
AB  - The protein human carbonic anhydrase II (HCA II) has been isotopically labeled
      with 2H, 13C and 15N for high-resolution NMR assignment studies and pulse
      sequence development. To increase the sensitivity of several key 1H/13C/15N
      triple-resonance correlation experiments, 2H has been incorporated into HCA II in
      order to decrease the rates of 13C and 1HN T2 relaxation. NMR quantities of
      protein with essentially complete aliphatic 2H incorporation have been obtained
      by growth of E. coli in defined media containing D2O, [1,2-13C2, 99%] sodium
      acetate, and [15N, 99%] ammonium chloride. Complete aliphatic deuterium
      enrichment is optimal for 13C and 15N backbone NMR assignment studies, since the
      13C and 1HN T2 relaxation times and, therefore, sensitivity are maximized. In
      addition, complete aliphatic deuteration increases both resolution and
      sensitivity by eliminating the differential 2H isotopic shift observed for
      partially deuterated CHnDm moieties.

PMID- 7647553
TI  - A high-resolution 1H NMR approach for structure determination of membrane
      peptides and proteins in non-deuterated detergent: application to mastoparan X
      solubilized in n-octylglucoside.
AB  - Application of 1H 2D NMR methods to solubilized membrane proteins and peptides
      has up to now required the use of selectively deuterated detergents. The
      unavailability of any of the common biochemical detergents in deuterated form has
      therefore limited to some extent the scope of this approach. Here a 1H NMR method
      is described which allows structure determination of membrane peptides and small
      membrane proteins by 1H 2D NMR in any type of non-deuterated detergent. The
      approach is based on regioselective excitation of protein resonances with DANTE-Z
      or spin-pinging pulse trains. It is shown that regioselective excitation of the
      amide-aromatic region of solubilized membrane proteins and peptides leads to an
      almost complete suppression of the two orders of magnitude higher contribution of
      the protonated detergent to the 1H NMR spectrum. Consistently TOCSY, COSY and
      NOESY sequences incorporating such regioselective excitation in the F2 dimension
      yield protein 1H 2D NMR spectra of quality comparable to those obtained in
      deuterated detergents. Regioselective TOCSY and NOESY spectra display all through
      bond and through-space correlations within amide-aromatic protons and between
      these protons and aliphatic and alpha-protons. Regioselective COSY spectra
      provide scalar coupling constants between amide and alpha-protons. Application of
      the method to the membrane-active peptide mastoparan X, solubilized in n
      octylglucoside, yields complete sequence-specific assignments and extensive
      secondary structure-related spatial proximities and coupling constants.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7647554
TI  - Hydration of the partially folded peptide RN-24 studied by multidimensional NMR.
AB  - Peptide-water interactions of a ribonuclease C-peptide analogue, RN-24 (Suc
      AETAAAKFLRAHANH2), which exhibits significant helicity, have been studied in
      solution using homonuclear 2D and 3D NMR cross-relaxation experiments. Dipolar
      peptide proton-water proton interactions are indicated by a large number of NOESY
      type cross peaks at the H2O resonance frequency, most of them with opposite sign
      relative to the diagonal. Some cross peaks arise from intrapeptide cross
      relaxation to labile protons of histidine, threonine, lysine and arginine side
      chains. The observed peptide-water interactions are rather uniformly distributed,
      involving peptide backbone and side chains equally. The data are consistent with
      rapid fluctuations of the conformational ensemble and the absence of peptide
      regions that are highly shielded from bulk solvent, even in a peptide that
      exhibits high propensities for formation of helical secondary structure.

PMID- 7647555
TI  - The effect of 17O on the relaxation of an amide proton within a hydrogen bond.
AB  - The relaxation rates of the multiple-quantum coherence for the amide hydrogen of
      Gly13 in ras p21.GDP were determined in the presence and absence of 17O labeling
      in the beta-phosphate of GDP. No significant difference could be observed between
      labeled and unlabeled samples, in spite of the fact that the hydrogen bond from
      the amide group of Gly13 to the beta-phosphate is shorter than is typical, based
      on its chemical shift. For macromolecules in which an oxygen atom is the acceptor
      of a hydrogen bond, dipolar coupling between 17O and hydrogen is unlikely to be
      observable, except for extremely short H-bonds.

PMID- 7647556
TI  - Rapid corepressor exchange from the trp-repressor/operator complex: an NMR study
      of [ul-13C/15N]-L-tryptophan.
AB  - [ul-13C/15N]-L-tryptophan was prepared biosynthetically and its dynamic
      properties and intermolecular interaction with a complex of Escherichia coli trp
      repressor and a 20 base-pair operator DNA were studied by heteronuclear isotope
      edited NMR experiments. The resonances of the free and bound corepressor (L-Trp)
      were unambiguously identified from gradient-enhanced 15N-1H HSQC, 13C-1H HSQC,
      13C- and 15N-edited 2D NOESY spectra. The exchange off-rate of the corepressor
      between the bound and free states was determined to be 3.4 +/- 0.52 s-1 at 45
      degrees C, almost three orders of magnitude faster than the dissociation of the
      protein-DNA complex. Examination of the experimental NOE buildup curves indicates
      that it may be desirable to use longer mixing times than would normally be used
      for a large molecule, in order to detect weak intermolecular NOEs in the presence
      of exchange. Intermolecular NOEs from bound corepressor to trp-repressor and DNA
      were analyzed with respect to the mechanism of ligand exchange. This analysis
      suggests that, in order for the ligand to diffuse out of the complex, there must
      be significant movement or 'breathing' of the protein and/or DNA.

PMID- 7647557
TI  - Sequential backbone assignment of isotopically enriched proteins in D2O by
      deuterium-decoupled HA(CA)N and HA(CACO)N.
AB  - It is demonstrated that sequential resonance assignment of the backbone 1H alpha
      and 15N resonances of proteins can be obtained without recourse to the backbone
      amide protons, an approach which should be useful for assignment of regions with
      rapidly exchanging backbone amide protons and for proteins rich in proline
      residues. The method relies on the combined use of two 2D experiments, HA(CA)N
      and HA(CACO)N or their 3D analogs, which correlate 1H alpha with the intraresidue
      15N and with the 15N resonance of the next residue. The experiments are
      preferably conducted in D2O, where very high resolution in the 15N dimension can
      be achieved by using 2H decoupling. The approach is demonstrated for a sample of
      human ubiquitin, uniformly enriched in 13C and 15N. Complete backbone and 13C
      beta/1H beta resonance assignments are presented.

PMID- 7647558
TI  - Lysine side-chain dynamics derived from 13C-multiplet NMR relaxation studies on
      di- and tripeptides.
AB  - 13C NMR relaxation data have been used to determine dipolar auto- and cross
      correlation times for the di- and tripeptides GK, KG, and GKG, primarily to
      analyze lysine side-chain motional dynamics. In general, correlation times are
      largest for backbone positions and decrease on going through the lysine side
      chain, consistent with the idea of increased mobility at C delta and C episilon
      methylenes. Correlation times, however, vary with the peptide ionization state.
      In the zwitterionic state of GK, for example, both auto- and cross-correlation
      times are at their maximum values, indicating reduced internal motions probably
      resulting from intramolecular electrostatic interactions. Modifying the charge
      state increases motional fluctuations. Activation energies determined from the
      temperature dependence of CH rotational autocorrelation times at neutral pH are
      approximately equal for glycine and lysine C alpha and lysine C beta and C gamma
      positions (4.1 +/- 0.2 to 4.5 +/- 0.2 kcal/mol) and tend to decrease slightly for
      lysine C delta and C epsilon (3.8 +/- 0.2 to 4.3 +/- 0.2 kcal/mol). The sign of
      lysine side-chain cross-correlations could not be explained by using any
      available rotational model, including one parameterized for multiple internally
      restricted rotations and anisotropic overall tumbling. Molecular and stochastic
      dynamics calculations were performed to obtain insight into correlated internal
      rotations and coupled overall tumbling and internal motions. Relatively strong
      correlations were found for i,i+1 backbone and lysine side-chain internal bond
      rotations. Stochastic dynamics calculations were more successful at explaining
      experimentally observed correlation times. In the fully charged state, a
      preferred conformation was detected with an all-trans lysine side chain.

PMID- 7647559
TI  - Probing internal water molecules in proteins using two-dimensional 19F-1H NMR.
AB  - A simple approach for detecting internal water molecules in proteins in solution
      is described. This approach combines 19F-detected heteronuclear Overhauser and
      exchange spectroscopy (HOESY) with site-specific 19F substitution. The model
      system employed was intestinal fatty acid-binding protein complexed with [2-mono
      19F]-palmitate. An intense cross peak was observed between the fluorine and a
      buried water molecule, as defined in the 1.98 A crystal structure of the complex.
      From HOESY spectra, the fluorine-water distance was estimated to be 2.1 A, in
      agreement with the crystal structure. This approach may be applicable to
      macromolecules that are too large for 1H-detected NMR methods.

PMID- 7647560
TI  - Refocusing revisited: an optimized, gradient-enhanced refocused HSQC and its
      applications in 2D and 3D NMR and in deuterium exchange experiments.
AB  - 2D 15N-1H correlation spectra are ideal for measuring backbone amide populations
      to determine amide exchange protection factors in studies of protein folding or
      other structural features. Most protein NMR spectroscopists use HSQC, which has
      been shown to be generally superior to HMQC in both resolution and sensitivity.
      The refocused HSQC experiment is intrinsically less sensitive than the regular
      HSQC, due to T2 relaxation during the refocusing delays. However, we show here
      that, when high 15N resolution is needed, an optimized refocused HSQC sequence
      that utilizes a semi-constant time evolution period and pulsed field gradients
      has better signal-to-noise ratio and resolution, and integrates more accurately,
      than a similar HSQC. The differences are demonstrated on a 20 kDa protein. The
      technique can also be applied to 3D NOESY experiments to eliminate strong NH2
      geminal peaks and their truncation artefacts at a modest cost in sensitivity.

PMID- 7647561
TI  - Processing and secretion of a virally encoded antifungal toxin in transgenic
      tobacco plants: evidence for a Kex2p pathway in plants.
AB  - Ustilago maydis is a fungal pathogen of maize. Some strains of U. maydis encode
      secreted polypeptide toxins capable of killing other susceptible strains of U.
      maydis. We show here that one of these toxins, the KP6 killer toxin, is
      synthesized by transgenic tobacco plants containing the viral toxin cDNA under
      the control of a cauliflower mosaic virus promoter. The two components of the KP6
      toxin, designated alpha and beta, with activity and specificity identical to
      those found in toxin secreted by U. maydis cells, were isolated from the
      intercellular fluid of the transgenic tobacco plants. The beta polypeptide from
      tobacco was identical in size and N-terminal sequence to the U. maydis KP6 beta
      polypeptide. Processing of the KP6 preprotoxin in U. maydis requires a subtilisin
      like processing protease, Kex2p, which is present in both animal and fungal cells
      and is required for processing of (among other things) small secreted polypeptide
      hormones and secreted toxins. Our findings present evidence for Kex2p-like
      processing activity in plants. The systemic production of this viral killer toxin
      in crop plants may provide a new method of engineering biological control of
      fungal pathogens in crop plants.

PMID- 7647562
TI  - A geminivirus induces expression of a host DNA synthesis protein in terminally
      differentiated plant cells.
AB  - Geminiviruses are plant DNA viruses that replicate through DNA intermediates in
      plant nuclei. The viral components required for replication are known, but no
      host factors have yet been identified. We used immunolocalization to show that
      the replication proteins of the geminivirus tomato golden mosaic virus (TGMV) are
      located in nuclei of terminally differentiated cells that have left the cell
      cycle. In addition, TGMV infection resulted in a significant accumulation of the
      host DNA synthesis protein proliferating cell nuclear antigen (PCNA). PCNA, an
      accessory factor for DNA polymerase delta, was not present at detectable levels
      in healthy differentiated cells. The TGMV replication protein AL1 was sufficient
      to induce accumulation of PCNA in terminally differentiated cells of transgenic
      plants. Analysis of the mechanism(s) whereby AL1 induces the accumulation of host
      replication machinery in quiescent plant cells will provide a unique opportunity
      to study plant DNA synthesis.

PMID- 7647563
TI  - Temporal relationship between the transcription of two Arabidopsis MADS box genes
      and the floral organ identity genes.
AB  - MADS box genes play important roles in specifying floral meristem and floral
      organ identity. We characterized the temporal and spatial expression patterns of
      two members of this gene family, AGL4 and AGL5 (for AGAMOUS [AG]-like). AGL4 RNA
      initially accumulates after the onset of expression of the floral meristem
      identity genes but before the onset of expression of the floral organ identity
      genes. AGL4 is, therefore, a putative target of the floral meristem identity
      genes and/or a potential regulator of the floral organ identity genes. AGL5 is
      initially expressed early in carpel development, shortly after the onset of AG
      expression. The loss of AGL5 expression in flowers of ag mutants, the activation
      of AGL5 by ectopic expression of AG, and the specific binding of AG to an element
      in the AGL5 promoter identify AGL5 as a putative direct target of AG. Our study
      provides possible links between the establishment of floral meristem and floral
      organ identity as well as subsequent steps in flower development.

PMID- 7647564
TI  - LRP1, a gene expressed in lateral and adventitious root primordia of arabidopsis.
AB  - We describe a gene that is expressed in lateral and adventitious root primordia
      of Arabidopsis. The gene was identified by expression of a transposon-borne
      promoterless beta-glucuronidase gene in lateral root primordia. The gene,
      designated LRP1 for lateral root primordium 1, and its corresponding cDNA were
      cloned and sequenced. The expression pattern of the gene in lateral root
      primordia was confirmed by in situ hybridization with LRP1 cDNA probes. The LRP1
      gene encodes a novel protein. LRP1 expression is activated during the early
      stages of root primordium development and is turned off prior to the emergence of
      lateral roots from the parent root. Insertion of the transposon in the LRP1 gene
      disrupted its expression. To evaluate the homozygous insertion line for a mutant
      phenotype, several aspects of wild-type lateral root development were analyzed. A
      mutant phenotype has not yet been identified in the insertion line; however,
      there is evidence that the gene belongs to a small gene family. LRP1 provides a
      molecular marker to study the early stages of lateral and adventitious root
      primordium development.

PMID- 7647565
TI  - Molecular characterization of BET1, a gene expressed in the endosperm transfer
      cells of maize.
AB  - A cDNA clone, BET1 (for basal endosperm transfer layer), was isolated from a cDNA
      bank prepared from 10-days after pollination (DAP) maize endosperm mRNA. BET1
      mRNA was shown to encode a 7-kD cell wall polypeptide. Both the mRNA and protein
      were restricted in their distribution to the basal endosperm transfer layer and
      were not expressed elsewhere in the plant. BET1 expression commenced at 9 DAP,
      reached a maximum between 12 and 16 DAP, and declined after 16 DAP. The initial
      accumulation of the BET1 polypeptide reached a plateau by 16 DAP and declined
      thereafter, becoming undetectable by 20 DAP. The antibody raised against the BET1
      protein reacted with a number of polypeptides of higher molecular mass than the
      BET1 monomer. Most of these were present in cytosolic fractions and were found in
      nonbasal cell endosperm extracts, but three species appeared to be basal cell
      specific. This result and the reactivity of exhaustively extracted cell wall
      material with the BET1 antibody suggest that a fraction of the protein is
      deposited in a covalently bound form in the extracellular matrix. We propose that
      the BET1 protein plays a role in the structural specialization of the transfer
      cells. In addition, BET1 provides a new molecular marker for the development of
      this endosperm domain.

PMID- 7647566
TI  - cycMs3, a novel B-type alfalfa cyclin gene, is induced in the G0-to-G1 transition
      of the cell cycle.
AB  - Cyclins are key regulators of the cell cycle in all eukaryotes. We have
      previously isolated two B-type cyclin genes, cycMs1 and cycMs2, from alfalfa that
      are primarily expressed during the G2-to-M phase transition and are most likely
      mitotic cyclin genes. Here, we report the isolation of a novel alfalfa cyclin
      gene, termed cycMs3 (for cyclin Medicago sativa), by selecting for mating type
      alpha-pheromone-induced cell cycle arrest suppression in yeast. The central
      region of the predicted amino acid sequence of the cycMs3 gene is most similar to
      the cyclin box of yeast B-type and mammalian A- and B-type cyclins. In situ
      hybridization showed that cycMs3 mRNA can be detected only in proliferating cells
      and not in differentiated alfalfa cells. When differentiated G0-arrested cells
      were induced to reenter the cell cycle in the G1 phase and resume cell division
      by treatment with plant hormones, cycMs3 transcript levels increased long before
      the onset of DNA synthesis. In contrast, histone H3-1 mRNA and cycMs2 transcripts
      were not observed before DNA replication and mitosis, respectively. In addition,
      cycMs3 mRNA was found in all stages of the cell cycle in synchronously dividing
      cells, whereas the cycMs2 and histone H3-1 genes showed a G2-to-M phase- or S
      phase-specific transcription pattern, respectively. These data suggest that the
      role of cyclin CycMs3 differs from that of CycMs1 and CycMs2. We propose that
      CycMs3 helps control reentry of quiescent G0-arrested cells into the G1 phase of
      the cell cycle.

PMID- 7647567
TI  - A nodule-specific gene encoding a subtilisin-like protease is expressed in early
      stages of actinorhizal nodule development.
AB  - To identify genes specifically expressed during early stages of actinorhizal
      nodule development, a cDNA library made from poly(A) RNA from root nodules of
      Alnus glutinosa was screened differentially with nodule and root cDNA,
      respectively. Seven nodule-enhanced and four nodule-specific cDNA clones were
      isolated. By using in situ hybridization, two of the nodule-specific cDNAs were
      shown to be expressed at the highest levels in infected cells before the onset of
      nitrogen fixation; one of them, ag12 (A. glutinosa), was examined in detail.
      Sequencing showed that ag12 codes for a serine protease of the subtilisin (EC
      3.4.21.14) family. Subtilisins previously appeared to be limited to
      microorganisms. However, subtilisin-like serine proteases have recently been
      found in archaebacteria, fungi, and yeasts as well as in mammals; a plant
      subtilisin has also been sequenced. In yeast and mammals, subtilases are
      responsible for processing peptide hormones. A homolog of ag12, ara12, was
      identified in Arabidopsis; it was expressed in all organs, and its expression
      levels were highest during silique development. Hence, our study shows that
      subtilases are also involved in both symbiotic and nonsymbiotic processes in
      plant development.

PMID- 7647568
TI  - Immunoprecipitation isolates multiple TSH receptor forms from human thyroid
      tissue.
AB  - Attempts to purify the thyroid-stimulating hormone receptor (TSHR) have been
      complicated by its susceptibility to proteolysis and its low level of expression
      in thyrocytes and many transfected cells. Controversy exists over its size and
      structure. Multiple, single-polypeptide forms of the TSHR (230, 187, and 95-100
      kDa) have been recently identified in immunoblots of crude plasma membranes
      prepared from COS-7 cells transfected with rat or human cDNA, but the
      relationship of these receptor species to the TSHR in human thyroid tissue has
      been heretofore unknown. We have developed a technique for immunoprecipitation of
      the TSHR which employed IgG purified from a polyclonal rabbit antiserum to TSHR
      residues 352-366. We have used immunoprecipitation to isolate the previously
      characterized 95-100 kDa TSH-holoreceptor, 187 kDa intermediate, and 230 kDa
      precursor forms of the TSHR from plasma membrane prepared from transfected COS-7
      cells and human thyroid tissue. The presence of all three forms was not altered
      by the addition of reducing agent to the sample buffer, demonstrating the single
      polypeptide structure of the TSHR. This is, to our knowledge, the first report of
      the purification from transfected COS-7 cells of these TSHR species identified
      previously only in immunoblots of crude plasma membrane, and the first report of
      the identification by any means of these TSHR forms in human thyroid tissue. The
      isolation of TSHR from human thyroid tissue requires confirmation by direct
      means, but promises to make the receptor available in a soluble form for studies
      of its structure and function.

PMID- 7647569
TI  - Role of octreoscan and correlation with MR imaging in Graves' ophthalmopathy.
AB  - Since the identification of somatostatin receptors on lymphocytes, orbital
      infiltration with mononuclear cells in Graves' ophthalmopathy has provided a
      rationale for receptor imaging with the radiolabeled somatostatin analog
      Octreotide. In 40 patients with Graves' ophthalmopathy and 10 controls, 110 MBq
      indium-Octreotide were administered i.v., and scans were performed at 4 and 24 h
      after injection. An uptake ratio between the orbits and the brain was determined.
      In 20 ophthalmophathy patients, magnetic resonance imaging (MRI) of the orbits
      was performed and the T2 relaxation time was measured within the rectus muscles.
      Compared to controls (4 h Octreotide uptake: median 6.0 counts/pixel/MBq,
      orbit/brain ratio 5.6), ophthalmopathy patients showed a 2- to 3-fold increased
      uptake (15.8 counts/pixel/MBq vs controls p = 0.0032; ratio 12.6, vs controls p =
      0.003). When considering patients with active disease only, a higher uptake was
      registered (16.8 counts/pixel/MBq vs controls p 0.0048, ratio 15.6 vs controls p
      = 0.0006). Untreated patients showed a markedly higher uptake (23
      counts/pixel/MBq) compared to patients receiving steroid therapy (12.6, p =
      0.001). MRI of the orbit revealed a correlation between T2 relaxation time of the
      eye muscles and orbital uptake of Octreotide (p < 0.001).

PMID- 7647571
TI  - Activated naive CD4+ peripheral blood T cells in autoimmune thyroid disease.
AB  - To better understand the clinical significance of changes in lymphocytes in
      thyroid disease this study analyzed the proportion of CD19+, CD3+, CD4+ and CD8+
      cells among circulating lymphocytes in Graves' disease (GD, n = 34) and
      autoimmune hypothyroidism (AH, n = 28) vs healthy subjects (n = 15). In addition,
      the expression of CD25 and CD45 isoforms on CD4+ T cells as well as their
      modulation by methimazole in patients with GD was measured using three color flow
      cytometry. It was observed that, irrespective of age, both patients with GD (17.6
      +/- 7.0% +/- SD) and those with AH (19.0 +/- 9.5%) had an increased percentage of
      the CD25+CD45RA+ (naive) subpopulation of helper cells vs healthy subjects (7.9
      +/- 2.3%, p < 0.0001). In patients with AH peripheral memory cells and hence
      overall CD25+ cells were more frequent among helper cells (56.7 +/- 12.2%) than
      in healthy subjects (40.8 +/- 14.0%, p < 0.001). Patients with GD (46.2 +/-
      13.4%) did not differ from normal subjects in this respect. Treatment of GD with
      MMI reduced the percentage of CD25+CD45RA+ cells among CD4+ cells toward values
      seen in healthy subjects. In addition, we confirm previous reports that CD8+
      cells toward values seen in healthy subjects. In addition, we confirm previous
      reports that CD8+ cells are significantly reduced in AH (23.9 +/- 4.9%) and
      untreated Graves' disease (23.2 +/- 6.6%) vs healthy subjects (32.2 +/- 5.9%, p <
      0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7647570
TI  - Prospective studies of thyroid function in patients receiving gold therapy.
AB  - Gold inhibits the Type I deiodinase that provides the bulk of circulating T3 in
      humans. We prospectively studied thyroid function in patients receiving
      increasing parenteral cumulative gold doses. Eight consecutive euthyroid patients
      with rheumatoid or psoriatic arthritis who were initiating intramuscular gold
      therapy were enrolled. Serum thyroid hormone levels (total T4, T3, and rT3) and
      TSH were measured for each subject at various levels during gold therapy. For
      analysis, the free T4 and free T3 indices, TSH concentrations, and T4/T3 ratios
      were correlated with cumulative gold dose. Neither individual nor pooled linear
      regressions showed a significant correlation between cumulative gold dose and any
      of the thyroid function parameters. Thyroid function is not affected in patients
      receiving up to 1500 mg of gold compounds. The most likely explanation for this
      is that gold principally accumulates in the Kupffer cells and renal cortex and
      these cells do not express Type I deiodinase.

PMID- 7647572
TI  - Fetal thyrotoxicosis: a case report and recommendations for prediction,
      diagnosis, and treatment.
AB  - A maternal history of Graves' disease places the fetus at risk for thyrotoxicosis
      in utero via the placental transfer of thyroid-stimulating immunoglobulins.
      Methods for prediction of fetal hyperthyroidism are available, but are not widely
      used. Clinical assessment of fetal thyroid status by monitoring of fetal heart
      rate and growth may be inaccurate. This raises some uncertainty in the initial
      diagnosis of fetal thyrotoxicosis and complicates the assessment of fetal
      response to maternal propylthiouracil therapy. A case illustrating these pitfalls
      in the diagnosis and management of fetal hyperthyroidism is presented. The
      condition was correctly diagnosed, but treatment based on fetal heart rate
      resulted in biochemical hypothyroidism in the infant at birth. Current
      recommendations for diagnosis and treatment of fetal hyperthyroidism are reviewed
      along with recent developments in the field. A modified approach is proposed.

PMID- 7647573
TI  - Thyroid hemiagenesis with subacute thyroiditis.
AB  - A 58-year-old woman with thyroid hemiagenesis associated with subacute
      thyroiditis is described. Physical examinations revealed a firm nodule with
      spontaneous pain and tenderness in the left thyroid lobe. A serum thyroid hormone
      levels were elevated and thyroid scintiscan with 99mTc pertechnetate showed an
      extremely low uptake, we made a diagnosis of subacute thyroiditis. A 201Tl
      thyroid scan demonstrated an enlarged left lobe and absence of the right lobe.
      Ultrasonography of the thyroid gland revealed an enlarged left lobe occupied
      mostly with a hypoechoic region. An incidental finding was absence of the right
      lobe. Two months later thyroid function returned to normal. A follow-up thyroid
      scintiscan revealed a normal left lobe but absent right lobe. The diagnosis of
      hemiagenesis was confirmed by CT scan. This appears to be the first case report
      of thyroid hemiagenesis associated with subacute thyroiditis.

PMID- 7647574
TI  - Identification of protein kinase C and its multiple isoforms in FRTL-5 thyroid
      cells.
AB  - Protein kinase C (PKC) has been implicated as an important regulator of signal
      transduction in the FRTL-5 thyroid cell line, but little is known about its
      isoforms in this cell line. In the present investigation, we characterized the
      activation of PKC by measuring the enzyme activity and identifying its isoforms
      in both cytosol and membrane fractions. Phorbol 12-myristate 13-acetate (PMA) was
      used as a PKC activator in this study. PKC activity assay revealed that PMA (300
      nM) induced a rapid translocation from cytosol to membrane within 1 min and led
      to an almost complete translocation within 15 min. Multiple PKC isoforms were
      examined by Western blot analysis with specific antibodies against alpha, beta,
      gamma, delta, epsilon, and zeta isoforms. PKC alpha, delta, epsilon, and zeta
      were identified in this cell line, but PKC beta and gamma were not. Exposure of
      the cells to PMA (300 nM) for 5 to 30 min led to the translocation of PKC alpha,
      delta, and epsilon from the cytosol to the membrane fraction, while PKC zeta was
      not affected. Treatment with PMA (300 nM) for 24 h resulted in the down
      regulation of PKC alpha, delta, and epsilon, but not PKC zeta. This study
      demonstrates for the first time direct evidence for the activation of PKC, and
      expression and distribution of its isoforms in FRTL-5 thyroid cells.

PMID- 7647575
TI  - Accurate and simple method of diagnosing thyroid nodules the modified technique
      of ultrasound-guided fine needle aspiration biopsy.
AB  - We describe an accurate and simple method of diagnosing thyroid nodules by the
      modified technique of ultrasound-guided fine needle aspiration biopsy (UG-FNAB).
      An Aloka SSD 2000 focus type scanner (Aloka Co., Tokyo, Japan) equipped with a 10
      MHz mechanical sector probe and a 7.5-MHz convex probe was used. First, a clear
      picture of the thyroid gland was taken with the use of the 10-MHz probe to
      determine the abnormalities. Then, a 7.5-MHz probe (1.5 x 0.8 cm of surface area)
      was used to guide the needle perpendicularly to the neck. This method enabled us
      to obtain samples from nodules greater than 5 mm. We applied this technique to
      1000 patients who had uncertain diagnosis by the conventional method of FNAB. The
      advantages of this method are as follows: (i) The use of a small probe (7.5 MHz)
      is most important, since a needle can be inserted by watching the monitor without
      an assistant. (ii) The biopsy site can be chosen precisely. (iii) Small thyroid
      cancers, i.e., 5 mm cancer, can be biopsied without any difficulty. (iv) A life
      threatening anaplastic carcinoma can be diagnosed at an early stage. (v) An
      intraglandular metastasis to the opposite lobe can be detected. (vi) Cystic
      carcinoma, difficult to diagnose by FNAB, can be diagnosed accurately. This
      method is highly recommended for all clinicians who are currently doing FNAB.

PMID- 7647576
TI  - Percutaneous ethanol injection (PEI): what is its role in the treatment of benign
      thyroid nodules?
AB  - Ultrasound-guided percutaneous ethanol injection (PEI) was first proposed by
      Livraghi in 1990 as a possible therapy for autonomously functioning thyroid
      nodules (AFTN). The procedure is performed on out-patients; is rapid; there is no
      need of anesthesia, nor of bed rest or patient observation after treatment. Under
      direct sonographic control a limited amount of 95% sterile ethanol (1-5 ml) is
      slowly injected into the nodule. In predominantly cystic nodules complete fluid
      removal is preliminarily performed, and thereafter ethanol is injected on the
      basis of the aspirated fluid volume without removing the needle. PEI-induced
      thyroid damage is characterized by coagulative necrosis and haemorrhagic
      infarction due to vascular thrombosis, and is well defined from the surrounding
      thyroid parenchyma. Several papers have confirmed the effectiveness of PEI.
      Normalization of serum TSH and thyroid hormones, marked decrease of nodule
      volume, and effacement of the previously hyperfunctioning area at thyroid
      scintiscan are reported in 64-85% of toxic AFTN. Nontoxic AFTN are successfully
      treated in 80-100% of the cases. PEI significantly superior to aspiration alone
      in inducing volume reduction of benign cystic thyroid nodules, and the recurrence
      rate is only 2.5-5%. Complications requiring hospitalization were not reported,
      but the importance of experienced operators must be stressed to avoid transient
      dysphonia due to recurrent laryngeal nerve damage. Prior to PEI malignancy must
      be ruled out by fine needle aspiration in all patients. Radioiodine and surgery
      remain the treatments of choice of large toxic thyroid nodules, but PEI can be
      effectively used in selected cases.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7647577
TI  - Possible limited bone loss with suppressive thyroxine therapy is unlikely to have
      clinical relevance.
AB  - To determine the effect of suppressive doses of thyroxine (T4) on bone mass, we
      studied 50 women on suppressive doses of T4 for 3-27 years (mean of 11 years).
      Twenty-five had nontoxic goiter and 25 had well-differentiated thyroid carcinoma.
      Fifty controls were matched for age, menopausal status, and body mass index. Bone
      mineral density (BMD) was measured in the lumbar spine (LS), femoral neck (FN),
      trunk (TK), and extremities (EXT) by dual-energy X-ray absorptiometry (DXA). In
      addition, the trunk area was measured by neutron activation analysis and recorded
      as a calcium bone index (CaBI). Twenty-one patients were restudied with DXA
      measurements at a mean of 1.5 +/- 0.5 (1 SD) years. The total population of 50
      patients showed no difference in bone mass from controls. In patients with
      nontoxic goiter, there was no evidence of any loss in bone mass. Cancer patients
      showed insignificant reductions of 2-5% in BMD of LS, FN, and TK and a
      significant 5% reduction in BMD of EXT, compared to controls, and a 12% reduction
      in CaBI compared to goiter patients. Cancer patients had a slightly higher (p <
      0.001) mean daily dose of T4 than goiter patients (0.23 vs 0.15 mg/day) but had a
      similar degree of TSH suppression. BMD and CaBI values did not correlate with
      free T4 index) with the daily T4 dose, accumulative dose, or with duration of T4
      therapy. There were no significant changes in bone mass in either goiter or
      cancer patients restudied after a mean of 1.5 years.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7647578
TI  - Point mutations in the thyrotropin receptor in human thyroid tumors.
AB  - The mechanism of the impaired response to thyrotropin (TSH) in thyroid tumor
      cells was investigated by searching for structural changes in the TSH receptor
      (TSH-R) in neoplastic thyroid tissues in humans. Total RNA was prepared from 34
      thyroid tissue samples (four normal, six adenoma, six follicular cancer, and 18
      papillary cancer) and reverse- transcribed into single-stranded cDNA, which was
      then used as a template for the polymerase chain reaction and subjected to single
      strand conformation polymorphism (SSCP) analysis. Two fragments, FRAG (468-692)
      (nucleotides 468 to 692, corresponding to the mid-portion of the receptor
      extracellular domain) and FRAG (2044-2295) (nucleotides 2044 to 2295,
      corresponding to the COOH-terminal, cytoplasmic domain of the TSH-R cDNA) showed
      differences in electrophoretic mobility among the various thyroid tissue samples.
      Direct sequencing revealed Phe197 (TTC) --> Ile(ATC), and Asp219 (GAT) -->
      Glu(GAG) substitutions in FRAG (468-692) from two papillary cancers. Three types
      of substitution were identified in FRAG(2044-2295): Asn715 (AAC) --> Asp(GAC)
      from one papillary cancer, Lys723 (AAG) --> Met(ATG) from one papillary cancer,
      and Asp 727 (GAC) --> Glu(GAG) from one normal tissue sample, one follicular
      cancer, and four papillary cancers. These results suggest that there exist
      structural changes in TSH-R in some cases of thyroid neoplastic tissue.

PMID- 7647580
TI  - Isolation and partial characterization of eosinophil granule proteins in rats-
      eosinophil cationic protein and major basic protein.
AB  - Peritoneal eosinophilia was induced in rats using Ascaris suum extract as an
      antigen, and characteristics of granule proteins of eosinophils collected from
      the peritoneal cavity were investigated. Peritoneal eosinophilia was induced by
      injection of the antigen solution into the peritoneal cavity of the immunized
      rats that had been orally administered with cyclophosphamide. Peritoneal cells
      were collected 48 h after injection of the antigen solution, incubated in plastic
      dishes, and nonadherent cells were collected as an eosinophil-rich fraction, from
      which granule proteins were extracted. Granule proteins were then purified by
      cation exchange chromatography, gel filtration, copper chelate affinity
      chromatography, and reverse-phase HPLC. Two distinct basic proteins of which
      molecular weights are 18- and 17-kD were obtained. Partial N-terminal amino acid
      sequence analysis revealed that the 18-kD protein and the 17-kD protein were
      homologous to the human eosinophil cationic protein (ECP) and the human and
      guinea pig major basic protein (MBP), respectively. Both the two proteins showed
      strong bactericidal activity against Escherichia coli and Staphylococcus aureus.
      These results indicate that rat eosinophils also possess ECP and MBP in their
      granules as well as human and guinea pig eosinophils.

PMID- 7647579
TI  - Mercuric-chloride-induced autoimmunity in mice involves up-regulated presentation
      by spleen cells of altered and unaltered nucleolar self antigen.
AB  - HgCl2 treatment of B10.S mice induces IgG autoantibodies to fibrillarin, a
      component of small nuclear ribonucleoprotein particles, and histone. Here, we
      demonstrate the activation by HgCl2 of autoreactive T cells specific for these
      nuclear proteins. Of nine CD4+ T cell hybridoma clones obtained from HgCl2
      treated B10.S mice, one clone reacted to histone Hl and eight clones to
      fibrillarin. One of the fibrillarin-specific clones only recognized fibrillarin
      pretreated with HgCl2 (Hg2+ fibrillarin), suggesting that Hg2+ can induce the
      presentation of a novel fibrillarin epitope. Four fibrillarin-specific hybridoma
      clones studied for cytokine production were shown to produce interleukin (IL)-2,
      and three of them also produced IL-4. For stimulation of fibrillarin-specific T
      cell hybridomas, exogenous murine fibrillarin had to be added when antigen
      presenting cells (APCs) came from untreated mice, but not when the APCs were
      obtained from HgCl2-treated animals. Apparently, HgCl2 treatment induces the
      presentation by APCs of a novel Hg2+ fibrillarin epitope and up-regulates the
      presentation of unaltered fibrillarin epitopes, thus activating 'Hg(2+)-specific'
      as well as autoreactive CD4+ T cells.

PMID- 7647581
TI  - Systemic immune response after rectocolonic administration of ovalbumin in mice.
AB  - The aim of our study was to determine the effect of a rectocolonic
      preimmunization with ovalbumin on the systemic immune response induced by a
      subsequent subcutaneous injection of this antigen in Balb/c mice. One
      rectocolonic, but not intragastric, administration of 25 mg of ovalbumin induced
      a detectable increase in serum anti-ovalbumin antibody level. The level reached
      was however much lower than after subcutaneous injection. Both intragastric and
      rectocolonic immunization with ovalbumin induced specific systemic cellular
      tolerance. However, after rectocolonic, but not intragastric, preimmunization
      there was no systemic humoral tolerance to this antigen. These differences in
      systemic immune responses after rectocolonic or intragastric administration of
      ovalbumin could be due to different stimulation of the systemic immune system or
      to differences between the colonic and small bowel mucosal immune system, which
      remain to be elucidated.

PMID- 7647582
TI  - Halogenated anesthetics form liver adducts and antigens that cross-react with
      halothane-induced antibodies.
AB  - Two halogenated anesthetics, enflurane and isoflurane, have been associated with
      an allergic-type hepatic injury both alone and following previous exposure to
      halothane. Halothane hepatitis appears to involve an aberrant immune response. An
      antibody response to a protein-bound biotransformation product (trifluoroacetyl
      adduct) has been detected on halothane hepatitis patients. This study was
      performed to determine cross-reactivity between enflurane and isoflurane with the
      hypersensitivity induced by halothane. The subcellular and lobular production of
      hepatic neoantigens recognized by halothane-induced antibodies following
      enflurane and isoflurane, and the biochemical nature of these neoantigens was
      investigated in two animal models. Enflurane administration resulted in
      neoantigens detected in both the microsomal and cytosolic fraction of liver
      homogenates and in the centrilobular region of the liver. In the same liver,
      biochemical analysis detected fluorinated liver adducts that were up to 20-fold
      greater in guinea pigs than in rats. This supports and extends previous evidence
      for a mechanism by which enflurane and/or isoflurane could produce a
      hypersensitivity condition similar to that of halothane hepatitis either alone or
      subsequent to halothane administration. The guinea pig would appear to be a
      useful model for further investigations of the immunological response to these
      antigens.

PMID- 7647583
TI  - Systemic neutrophilia observed during anaphylactic shock in rats is inhibited by
      dopaminergic antagonists.
AB  - The involvement of the sympathetic and dopaminergic systems on blood neutrophilic
      leucocytosis observed during anaphylaxis was investigated. Blood neutrophil
      counts impressively increased 1 h after intravenous injection of ovalbumin (OVA,
      250 micrograms/kg) into OVA-immunized rats. The increase in neutrophil counts
      induced by OVA was abrogated after catecholamine depletion by reserpine. Either
      adrenalectomy or the alpha- and beta-adrenoceptor antagonists phentolamine and
      propranolol, respectively, had only minor inhibitory effects on neutrophilia
      induced by antigen. On the other hand, pretreatment with the dopaminergic
      antagonists chlorpromazine and pimozide significantly inhibited the neutrophilia.
      The intravenous injection of apomorphine, a dopaminergic agonist, increased
      neutrophil counts in naive animals, while chlorpromazine completely inhibited
      this phenomenon. These results suggest that dopaminergic mechanisms play a role
      in the systemic neutrophilia observed during anaphylactic shock.

PMID- 7647584
TI  - Soluble T-cell markers and serum cytokines in type I (insulin-dependent) diabetes
      mellitus.
AB  - Markers of cell-mediated immune activation were studied in 32 Chinese patients
      with recent-onset insulin-dependent diabetes mellitus (IDDM) as compared with 12
      patients with recent-onset non-insulin-dependent diabetes mellitus (NIDDM) and 34
      normal subjects. Sera were assessed for soluble markers of T-cell activation
      (sCD4, sCD8, sIL-2R); the cytokines (IL-1 beta, TNF-alpha, IL-2, IL-6), and T
      cell subsets were also determined. Only 1 of the 32 IDDM patients had increased
      sCD4 levels, 5 had increased sCD8, and 3 had increased sIL-2R. None of the sera
      from NIDDM patients and control subjects showed such increased levels of soluble
      markers. Three IDDM patients had detectable IL-1 beta and this weakly so (< 3.5
      pg/ml). However, the other cytokine data and the frequency of activated T-cells,
      CD4+, CD8+ T-cell subsets and CD4:CD8 ratio showed no significant differences
      among the IDDM, NIDDM and normal subjects. Our data suggest that in addition to a
      low frequency of islet cell antibodies, Chinese patients with recent onset IDDM
      also showed a lack of serum markers of cellular activation.

PMID- 7647585
TI  - Immunobiochemical characterization of Brassica campestris pollen allergen.
AB  - Brassica campestris (BC), Eng. Mustard, is an important source of pollen
      allergen, responsible for type I hypersensitivity disorders. In the present
      study, BC pollen extract was characterized by TLIEF, SDS-PAGE and immunoprinting.
      The extract separated into 50 silver stained bands of pI 3-9 on isoelectric
      focusing whereas it resolved into 14 Coomassie blue stained protein bands of 14
      100 kD on SDS-PAGE. Immunoblot analysis with individual patient sera detected
      four allergenic proteins of 90, 67, 60 and 14 kD. BC separated into 8 peaks (Bras
      1-8) on DEAE Sephadex A-50 column. Bras 2 was found to be most potent by IgE
      specific ELISA, hence further fractionated on Sephadex G-200. A protein of 90 kD
      (Bras 2a) isolated by gel filtration was found to be most allergenic protein by
      ELISA inhibition. The findings shall be applicable in standardization of future
      batches of BC pollen extract to be used for allergy diagnosis and immunotherapy.

PMID- 7647586
TI  - Characterization of the allergen group VI in timothy grass pollen (Phl p 6). II.
      cDNA cloning of Phl p 6 and structural comparison to grass group V.
AB  - The complete primary structure of the major allergen Phl p 6 was determined by
      cDNA cloning. A cDNA library of timothy grass pollen was screened by a Phl p 6
      directed mouse antiserum. Six clones were obtained. From the cDNA data we deduced
      a protein sequence of 110 amino acids. While the size of the leader sequences
      varied considerably between the different clones, only one amino acid exchange
      affected the mature proteins. Sequence comparison of group VI and V allergens
      showed a high degree of homology in the N- and C-terminal regions. The structural
      data strongly indicate that group VI and V are independent groups of allergens,
      which have derived from a common precursor gene.

PMID- 7647587
TI  - Induction of leucocyte recruitment and bronchial hyperresponsiveness in the
      guinea pig by aerosol administration of interleukin-2.
AB  - Exposure of guinea pigs to an aerosol of human recombinant interleukin-2 (IL-2;
      30 micrograms) resulted in an increase in the numbers of eosinophils and
      macrophages recovered from bronchoalveolar lavage fluid (BALF) 24 h later. This
      was accompanied by a bronchial hyperresponsiveness to intravenous acetylcholine.
      In guinea pigs sensitized to ovalbumin, exposure to IL-2 caused an increase in
      the number of macrophages, but not eosinophils in BALF and bronchial
      hyperresponsiveness to acetylcholine did not develop. In guinea pig skin,
      intradermal injection of IL-2 (10(-14) to 10(-9) mol/site) had no effect on 111In
      eosinophil accumulation, measured over 3 h, suggesting that IL-2 does not act
      directly to recruit eosinophils. The hypothesis that IL-2 may be acting via
      release of interleukin-5 (IL-5) was tested using an antibody to IL-5 (TRFK-5; 1
      mg/kg). Treatment with TRFK-5 1 h before exposure to IL-2 aerosol had no effect
      on the numbers of macrophages or eosinophils recovered from BALF 24 h later,
      although there was a tendency for reduced bronchial hyperresponsiveness to
      acetylcholine. These results suggest that (1) IL-2 is not a directly acting
      chemoattractant for eosinophils in the guinea pig, (2) the action of IL-2 to
      increase bronchial hyperresponsiveness is also indirect, partly via generation of
      IL-5, and (3) immunological sensitization alters the response of both eosinophils
      and bronchial smooth muscle to IL-2.

PMID- 7647588
TI  - Effect of a selective thromboxane A2 receptor antagonist BAY u3405 on antigen-,
      leukotriene C4- and leukotriene D4-induced bronchoconstriction in guinea pigs.
AB  - We studied the effect of a selective thromboxane (TX) A2 receptor antagonist BAY
      u3405 on prostanoid-, leukotriene (LT) C4, LTD4- and antigen-induced
      bronchoconstriction in nonanesthetized guinea pigs in vivo. Oral administration
      of BAY u3405 inhibited bronchoconstriction induced by inhaled TXA2 mimetic
      U46619, prostaglandin (PG) D2 and PGF2 alpha. BAY u3405 also decreased the
      bronchoconstriction induced by inhaled LTC4 and LTD4. Intraperitoneal
      administration of TXA2 synthetase inhibitor OKY-046 did not affect PGD2- and PGF2
      alpha-induced bronchoconstriction, but attenuated LTC4- and LTD4-induced
      bronchoconstriction. BAY u3405 and OKY-046 decreased antigen-induced
      bronchoconstriction in actively sensitized guinea pigs. These results indicate
      that BAY u3405 not only inhibits TXA2-, PGD2- and PGF2 alpha-induced
      bronchoconstriction that is mediated through a TXA2 receptor but also decreases
      LTC4. LTD4- and antigen-induced bronchoconstriction which is mediated in part
      through TXA2 synthesis. These results suggest that BAY u3405 might be useful in
      controlling prostanoid-induced bronchoconstriction in asthma.

PMID- 7647589
TI  - In vitro allergy testing needs better standardization--test results from
      different laboratories lack comparability mostly due to missing effective
      standards.
AB  - Correct determination of specific IgE is important for the diagnosis of allergic
      diseases. Different detection systems are supposed to yield similar results of
      this standardized parameter. In order to investigate this assumption, 40 sera
      from allergic patients were sent in eight mailings to 23 laboratories over a 2
      year period. Three IgE determinations in each serum had to be performed according
      to laboratory-specific methods. Whereas 'wrong' results were rare with any of the
      methods and the overall results to a large degree comparable, sensitivity and
      specificity seemed to vary considerably between antigens, methods, companies and
      laboratories. According to our observations, better standardization of test
      reagents and test methods by the suppliers is essential in order to harmonize the
      test results and to avoid wrong conclusions. At present, the diversity of
      techniques that are used for IgE determination leads to quite divergent results,
      and the allergist has to know that. And finally, the legislator is urged to
      better control these diagnostic tools, because wrong results may lead to life
      threatening situations.

PMID- 7647590
TI  - Different reactivity to recombinant Aspergillus fumigatus allergen I/a in
      patients with atopic dermatitis or allergic asthma sensitised to Aspergillus
      fumigatus.
AB  - We report a clinical study comparing the skin test reactivity to recombinant
      Aspergillus fumigatus allergen 1 (rAsp fI/a) in patients with atopic dermatitis
      and A. fumigatus sensitisation (n = 15), A. fumigatus-allergic patients with
      asthma (n = 10) and healthy control subjects (n = 10). All patients sensitised to
      A. fumigatus reacted at intradermal skin tests with commercial A. fumigatus
      extracts in contrast to the healthy subjects. Six out of 10 patients with well
      characterised A. fumigatus allergic asthma were sensitised to rAsp fI/a as shown
      by a positive skin test. The patients with skin test reactivity to rAsp fI/a also
      showed rAsp f I/a-specific serum IgE as determined by ELISA. None of the patients
      with atopic dermatitis, healthy control subjects and 4 out of 10 A. fumigatus
      allergic asthmatics reacted in intradermal tests to rAsp fI/a. Serologic
      investigations revealed that these subjects did not express detectable amounts of
      rAsp fI/a-specific IgE in agreement with the negative skin test results. Extended
      serologic investigations have not shown significant differences in rAsp fI/a
      specific IgA, IgG4 and IgG1 serum levels between atopic dermatitis patients and
      healthy control subjects. The results suggest that sensitisation to A. fumigatus
      in patients with atopic dermatitis is not related to the major A. fumigatus
      allergen I in contrast to the high incidence of sensitisation to Asp fI/a
      occurring in allergic asthmatics.

PMID- 7647591
TI  - Conditioned enhancement of cough response in awake guinea pigs.
AB  - To determine whether psychological factors affect the cough response, we employed
      a classical conditioning procedure in which capsaicin challenge was paired with
      the presentation of an odor in awake guinea pigs. On days 1-4, animals received
      combined administrations of the unconditioning stimulus, capsaicin aerosols, and
      the conditioning stimulus, camphor aerosols (group 1), capsaicin and saline
      aerosols (group 2), and camphor and saline aerosols (group 3), and the number of
      coughs was counted. On day 5, all groups received camphor and saline aerosols. A
      significant number of coughs (p < 0.01) was observed only in group 1 when the
      animals were exposed to the odor alone on day 5. This suggests that associative
      learning enhances the cough response.

PMID- 7647592
TI  - Systemic lupus erythematosus and thymoma--a double-edged sword.
AB  - The coexistence of systemic lupus erythematosus (SLE) and thymoma is rare. We
      describe 2 female patients with this combination. A 48-year-old woman presented
      with dyspnea due to a left pleural effusion. Her past history revealed over the
      previous 3 years the development of anemia, thrombocytopenia, alopecia,
      pericardial effusion and proteinuria. Four months prior to this hospitalization,
      the patient was first admitted due to purpura. At that time, laboratory tests
      revealed an elevated sedimentation rate, elevated titers of ANA and anti-DNA.
      Chest X-ray demonstrated a widened mediastinum, and upon operation an
      encapsulated thymoma was excised. Four months following the thymectomy, the
      patient is unresponsive despite high dose steroid therapy. Another patient, a 30
      year-old woman, presented with SLE (cutaneous, arthritis, anemia, positive ANA
      and high titers of anti-DNA) and thymoma simultaneously. Six years after
      thymectomy the patient is in SLE remission. Thymectomy in mice prone to
      autoimmunity (NZB/W mice) has been shown to accelerate the autoimmune
      manifestations. Conversely, the opposite effect is seen in MRL/lpr mice. The
      immunological effect of adult thymectomy on the course of human SLE remains to be
      established, on a larger series of patients. It seems that the heterogenicity of
      human patients is exemplified by the contrasting effects of thymectomy for
      thymoma in SLE patients.

PMID- 7647593
TI  - Heart transplantation in an 8-month-old girl. 10th anniversary report.
AB  - In 1984, Dr. Denton A. Cooley led a surgical team that implanted a cardiac
      allograft in an 8-month-old girl who had end-stage cardiac disease secondary to
      endocardial fibroelastosis. At that time, experience with cardiac transplantation
      in infants was limited, and the long-term effects of the procedure were cause for
      concern. Ten years later, our patient is a healthy 4th-grade student who enjoys a
      remarkably normal life. She has grown and developed quite satisfactorily, and her
      heart has enlarged in proportion to her overall somatic growth. Long-term
      immunosuppression has produced no adverse effects, and the child's medical
      problems have differed little from those of her peers. This landmark case has
      yielded preliminary answers to a number of important questions about cardiac
      transplantation in infants and has confirmed our original opinion that the
      procedure is well warranted in selected patients.

PMID- 7647594
TI  - Myocardial regeneration. Transplanting satellite cells into damaged myocardium.
AB  - Millions of Americans suffer from chronic heart failure. Despite treatments with
      heart transplantation, cardiomyoplasty, and artificial assist devices, an ideal
      therapy is yet to be found. Since 1988, we have studied the transplantation of
      myogenic stem cells from skeletal muscle into injured myocardium in the hope that
      these cells would multiply and differentiate, thereby improving the function of
      the failing heart. We have achieved 2 goals thus far: the 1st was improving the
      culture technique to obtain high yield and purity of the satellite cells; the 2nd
      was successfully implanting cultured satellite cells in dog hearts and later
      identifying them as new myocardium. We share our findings here to encourage more
      study in this promising area.

PMID- 7647595
TI  - Potential mechanisms of improvement after various treatments for hypertrophic
      obstructive cardiomyopathy.
AB  - In sum, systolic dysfunction of the ventricle associated with left ventricular
      outlet obstruction and often with mitral valve regurgitation may be improved by
      myotomy, myomectomy, mitral valve replacement, and perhaps by the creation of
      left bundle branch block via DDD right ventricular pacing. Diastolic dysfunction
      of the ventricle may be improved by prolonging the diastolic filling period,
      shortening the isovolumic relaxation period with calcium channel blocking drugs,
      or perhaps by altering the atrioventricular activation time with a DDD pacemaker.
      The symptoms and complications of associated arrhythmias may be improved by
      medication, particularly with beta-blockers, which tend to stabilize the atrial
      rhythm and perhaps the ventricular rhythms. In treating patients with
      demonstrated ventricular arrhythmias, other antiarrhythmic agents may be helpful.
      (Table II summarizes the abnormalities, causes, and treatments of hypertrophic
      obstructive cardiomyopathy.) Epicardial coronary atherosclerosis is not rare in
      these patients, and arteriographic confirmation may lead to improvement by
      surgical bypass treatment. Since stroke volume is nearly fixed, cardiac output
      depends very much on heart rate. For this reason, each patient needs to receive
      the appropriate dosage of medications to achieve the optimal heart rate for his
      or her own physiologic state.

PMID- 7647596
TI  - Assessment of intracardiac masses by transesophageal echocardiography.
AB  - Transesophageal echocardiography and 2-dimensional transthoracic echocardiography
      have proved to be extremely valuable in the diagnosis of cardiac masses. In this
      report, we review the echocardiographic findings, clinical history, and
      histopathologic findings in 21 patients with intracardiac masses who underwent
      transthoracic echocardiography, transesophageal echocardiography, or both, at our
      institution. Of these patients, 14 had benign masses and 7 had malignant tumors.
      The potential role of transesophageal echocardiography in the diagnosis and
      treatment of patients with intracardiac masses is discussed. We believe that
      transesophageal echocardiography offers the cardiologist and cardiovascular
      surgeon the capability of more accurate preoperative and intraoperative
      assessment of cardiac masses.

PMID- 7647597
TI  - New developments in the diagnosis and management of cardiac allograft
      vasculopathy.
AB  - The major cause of late death in cardiac transplant recipients is cardiac
      allograft vasculopathy, also referred to as cardiac transplant atherosclerosis,
      which occurs in as many as 45% of transplant recipients who survive longer than 1
      year. It differs from typical atherosclerosis in that intimal hyperplasia is
      concentric and diffuse, the internal elastic lamina remains intact, calcification
      is rare, and the disease tends to develop rapidly. Intravascular ultrasound and
      coronary angioscopy are more sensitive diagnostic measures of cardiac allograft
      vasculopathy than is coronary angiography. Although retransplantation at present
      seems to be the only definitive therapy for cardiac allograft vasculopathy, it
      has shown only fair results. Recent studies have suggested that calcium entry
      blockers and angiotensin-converting enzyme inhibitors may play a beneficial role
      in delaying the progression of cardiac allograft vasculopathy.

PMID- 7647599
TI  - Retrograde replacement of the thoracic aorta.
AB  - A technique is described for replacement of the entire thoracic aorta. In this
      "pull-through" technique, which utilizes hypothermic circulatory arrest, the
      graft is implanted in a retrograde fashion, thus providing protection for the
      spinal cord and brain and avoiding injury to the vagus and phrenic nerves.

PMID- 7647600
TI  - Deringing procedure for congenital pulmonary vein stenosis.
AB  - We operated on a 14-year-old boy who had an echocardiographic diagnosis of
      ventricular septal defect. At surgery we found, in addition, an anomalous and
      obstructive intraventricular muscle bundle. Detection of a continuous thrill over
      the right pulmonary veins, prior to cardiopulmonary bypass, led to exploration of
      the left atrium. The ostia of the right superior and inferior pulmonary veins
      were impeded by circumferential membranous rings of endocardium with central
      stenotic openings. Excision of these annular rings relieved the obstruction. The
      left lung was drained by a long intrapericardial common venous channel that
      entered the left atrium through a stenotic ostium; excision of an annular ridge
      of endocardium restored normal flow. The patient remains asymptomatic after 23
      months. The case is reported for the new deringing technique and the rarity of
      successful correction of congenital pulmonary vein stenosis.

PMID- 7647598
TI  - Revascularization therapy for coronary artery disease. Coronary artery bypass
      grafting versus percutaneous transluminal coronary angioplasty.
AB  - Coronary artery bypass surgery relieves the symptoms of myocardial ischemia and
      prolongs survival of patients with more severe coronary artery disease.
      Randomized trials of surgical therapy have consistently shown that the benefits
      of surgical revascularization are proportional to the amount of myocardium
      affected by, or at risk for, ischemic injury. This risk is inferred from
      angiographically delineated coronary anatomy, estimates of left ventricular
      function, and physiologic testing. The population that may see a survival benefit
      from surgical revascularization has probably been expanded beyond that reported
      in the VA, CASS, and ECSS trials, due to improved perioperative care, longer
      graft survival, and the use of internal mammary artery grafts. Percutaneous
      transluminal coronary angioplasty revascularizes myocardium by dilating a
      stenotic segment of coronary artery. While successful in relieving the symptoms
      of myocardial ischemia, PTCA is hindered by the occurrence of abrupt vessel
      closure and the frequent development of restenosis. Furthermore, firm proof of a
      survival benefit, outside of emergency therapy for acute myocardial infarction,
      is not yet available. However, because the risk of procedure-related death or
      serious complication is lower than that seen with bypass surgery, PTCA provides a
      useful alternative revascularization method for patients with less extensive
      disease, in whom the risk of surgery may equal or exceed any beneficial effect.
      New technology and growing experience are widening the scope of percutaneous
      revascularization by extending the hope of symptomatic relief and survival
      benefit even to patients with extensive, severe coronary artery disease.
      Comparisons between surgical therapy and PTCA in select populations with single-
      and multivessel coronary artery disease have shown that PTCA is not as effective
      as surgery for long-term symptomatic control, and that it often requires repeat
      PTCA or cross-over to bypass surgery; however, long-term outcomes (i.e., death
      and myocardial infarction) are similar. The cost of treatment beginning with PTCA
      may be lower than that of initial surgery, even when the increased need for
      repeat revascularization is taken into account. Despite this, surgical bypass
      remains the mainstay of therapy for patients with severe coronary artery disease
      and a poor prognosis for survival, and will remain the fallback procedure for
      patients who repeatedly undergo failed PTCA. At the present time,
      revascularization should be offered on the basis of symptom severity (in the
      presence of medical therapy) and in accordance with the prognosis for survival as
      judged by the extent and severity of disease (Table VI). Percutaneous
      transluminal coronary angioplasty is preferred in patients who require
      revascularization but can obtain no proven benefit from bypass surgery. Coronary
      artery bypass surgery, using the internal mammary artery when possible, remains
      the revascularization method of choice for patients with more severe disease or
      whose disease is not amenable to treatment using percutaneous methods (Table
      VII).

PMID- 7647602
TI  - Pulmonary autograft aortic valve replacement. Early experience with the Ross
      procedure.
AB  - Aortic valve replacement with a pulmonary autograft was performed in 24 patients
      between October 1993 and October 1994, at the All India Institute of Medical
      Sciences, New Delhi. There were 20 (83.3%) males and 4 (16.7%) females. Their
      ages ranged from 10 to 56 years (mean, 21.46 +/- 11.45 years). Associated
      procedures included 10 mitral valve procedures (4 open commissurotomies, 5 mitral
      valve repairs, and 1 homograft mitral valve replacement) and 1 tricuspid valve
      repair. There were 4 (16.7%) early deaths, 3 of which were due to bleeding or its
      sequelae and 1 due to septicemia. There were no late deaths. Follow-up ranged
      from 1 to 13 months (mean, 198.3 +/- 111.1 days). Nineteen (95%) patients are in
      New York Heart Association functional class I, and 1 patient (5%) is in class II,
      due to poor left ventricular function. Only 1 patient showed grade 2/4 aortic
      regurgitation on follow-up examinations, and none has shown progression of aortic
      regurgitation. Our early results with the pulmonary autograft are encouraging;
      however, long-term evaluation is needed.

PMID- 7647601
TI  - Postpericardiotomy syndrome in pediatric heart transplant recipients. Immunologic
      characteristics.
AB  - Clinical features of postpericardiotomy syndrome (PPS) occur in pediatric heart
      transplant recipients despite immunosuppression, which raises questions about the
      mechanism of PPS. We studied the clinical and immunologic characteristics of 15
      pediatric heart transplant patients, ages 1.1 to 17.8 years (mean, 7.5 years); 7
      had clinical evidence of PPS (PPS+), and 8 were without clinical features of PPS
      (PPS-). Indicators of PPS included fever, irritability, pericardial friction rub,
      leukocytosis without other cause, and pericardial effusion. The onset of PPS was
      from 9 to 26 postoperative days (mean, 16 days). Immunosuppressive regimens were
      comparable up to the day of PPS diagnosis in PPS+ patients, and up to day 16 in
      PPS- patients (average onset of PPS in PPS+ patients). No differences were found
      between groups with respect to weight-adjusted dosages of cyclosporin A,
      azathioprine, or corticosteroids. Mean cyclosporin A levels in PPS+ and PPS-
      patients were 142 +/- 88 ng/mL (mean +/- standard deviation) and 265 +/- 122
      ng/mL (p = 0.045), respectively. Echocardiographic data on 3 PPS+ patients within
      1 day of PPS diagnosis revealed pericardial effusions ranging from 5 to 24 mm. No
      data were available on the remaining 4 PPS+ patients. Minimal pericardial
      effusions (< 10 mm) were seen in 4 PPS- patients during a comparable time period.
      One PPS- patient required pericardiocentesis. Endomyocardial biopsy rejection
      grade did not differ between groups. Means pretransplant soluble interleukin-2
      receptor levels did not differ between PPS+ and PPS- patients (758 +/- 410 vs 653
      +/- 270 IU/mL); nor did the PPS+ pretransplant levels differ from levels obtained
      1 or 2 months postoperatively (700 +/- 437 and 751 +/- 367 IU/mL, respectively).
      Although pretransplant percentages of the standard T-cell (CD2, CD3, CD4, CD8)
      and B-cell (DR and CD19) markers differed from post-transplant values, the
      changes could be explained by the immunosuppressive regimen and did not differ
      between PPS+ and PPS- patients. In the PPS+ patients, however, there were
      significant increases in the proportion of activated helper T cells (CD4+/25+)
      and cytotoxic T cells (Leu-7+/CD8+) following heart transplantation in comparison
      with pretransplant levels. We speculate that these changes in activation marker
      in PPS+ patients suggest a possible role for cell-mediated immunity in the
      pathogenesis of PPS in this group of patients.

PMID- 7647603
TI  - Endothelial injury, vasoconstriction, and its prevention.
AB  - The endothelial cell is an important determinant of vascular tone, and performs
      this function by the elaboration of several factors that modulate the contractile
      state of the vascular smooth muscle cell. In response to physical and molecular
      factors in the vasculature, the endothelial cell maintains basal vascular tone by
      the elaboration of prostacyclin, endothelium-derived relaxing factor, and
      endothelium-derived hyperpolarizing factor, all of which reduce vascular smooth
      muscle tone. With progressive dysfunction of or injury to the endothelium,
      however, vascular smooth muscle tone increases in response to reduced production
      or availability of these endothelium-derived vasorelaxants and increased
      production of the vasoconstrictor substances, endothelin and endothelium-derived
      constricting factor(s). Common determinants of endothelial dysfunction that
      contribute substantially to the progress of vascular diseases include
      hypercholesterolemia, hypertension, tobacco use, and diabetes mellitus. Current
      approaches to the reversal or attenuation of the progression of vascular diseases
      in which the endothelium plays an important role focus on pharmacotherapeutic
      methods by which to restore normal endothelial function.

PMID- 7647604
TI  - Coronary artery bypass grafting in patients with systemic lupus erythematosus.
      Report of 2 cases.
AB  - Systemic lupus erythematosus is an autoimmune disease that often involves the
      cardiovascular system. Coronary artery narrowing in patients with lupus
      erythematosus is severe, progressive, and related to the duration of the disease
      rather than to the age of the patient. Steroid use in such patients has improved
      their life expectancy but seems to be increasing the incidence of coronary
      involvement. Consequently, a larger number of systemic lupus erythematosus
      patients may be candidates for myocardial revascularization in the future. We
      report our experience with myocardial revascularization in 2 women with severe
      systemic lupus erythematosus, incapacitating angina, and severe obstructive
      coronary artery disease. One of the women required balloon angioplasty 19 months
      after coronary artery bypass grafting and remains asymptomatic nearly 3 years
      later. The other patient is free of symptoms 9 months after surgery. Our results
      with these 2 patients are encouraging. Long-term follow-up should yield further
      information regarding the benefits of myocardial revascularization and coronary
      angioplasty in patients with systemic lupus erythematosus.

PMID- 7647605
TI  - Coronary artery revascularization followed by single-lung transplantation in a
      patient with combined end-stage idiopathic pulmonary fibrosis and left main
      coronary artery stenosis.
AB  - Single-lung transplantation has been used successfully in patients who have
      idiopathic pulmonary fibrosis; however, coronary artery disease is often
      considered a contraindication for lung transplantation in such patients. We
      report the case of a 53-year-old man with idiopathic pulmonary fibrosis in whom
      left main coronary artery stenosis was found incidentally during pretransplant
      evaluation. The patient was treated successfully with elective coronary artery
      bypass grafting, followed by left single-lung transplantation 35 days later.

PMID- 7647606
TI  - Sinoatrial malfusion presenting with caudal position of right atrial appendage.
AB  - A 5-year-old boy underwent surgery at our institution for closure of an ostium
      secundum atrial septal defect. Median sternotomy revealed that the right atrial
      appendage lay at the acute margin of the heart. Atriotomy revealed that the
      crista terminalis was also displaced clockwise, extending from the left of the
      superior vena caval orifice anteriorly along the interatrial septum, to the left
      border of the inferior vena cava; the musculi pectinati radiated forward and to
      the right. This highly unusual anomaly is likely due to clockwise rotation of the
      atrial portion in relation to the normally positioned sinus venarum portion of
      the atrium, which resulted in sinoatrial malfusion.

PMID- 7647607
TI  - Successful thrombolysis for prosthetic pulmonary valve obstruction.
AB  - Thrombosis is a serious complication of prosthetic heart valve operations. In
      recent years, systemic thrombolysis has emerged as a suitable alternative to
      surgery. Experience with thrombosis of pulmonary prosthetic valves is very
      limited. We report a case of successful administration of intravenous
      streptokinase for thrombosis of a St. Jude Medical prosthetic valve 3 weeks after
      pulmonary valve replacement.

PMID- 7647608
TI  - Left thoracotomy for coronary revascularization after esophagoplasty with
      substernal colon interposition.
AB  - A 66-year-old man was referred to our institution with recurrent angina pectoris
      caused by 95% stenosis of the left anterior descending coronary artery. Twelve
      years earlier, he had undergone esophagoplasty with substernal colon
      interposition for an esophageal burn caused by a caustic substance. A left
      thoracotomy approach and femoro-femoral bypass were used safely for coronary
      artery revascularization.

PMID- 7647609
TI  - Thrombosis of the abdominal aorta. A rare complication of the intraaortic balloon
      pumping device.
AB  - We describe a patient who died due to thrombosis of the abdominal aorta and its
      branches after placement of an intraaortic balloon pumping device. This rare
      complication, which occurred despite careful insertion technique, underscores the
      need to select balloon size as a function of the individual patient's morphology.

PMID- 7647610
TI  - Pacemaker infection.

PMID- 7647611
TI  - Oscillation of pacing cycle length as an indicator of battery depletion.

PMID- 7647612
TI  - Amiodarone and the heart.

PMID- 7647613
TI  - Too hot, too cold, or just right?

PMID- 7647614
TI  - Preventing injuries in rural Canada.

PMID- 7647615
TI  - Unnecessary ordering of tests.

PMID- 7647616
TI  - Discouraging epidural use.

PMID- 7647617
TI  - Recognizing postpolio syndrome.

PMID- 7647618
TI  - Balancing health care efficiency and cost.

PMID- 7647620
TI  - Taking age into account.

PMID- 7647619
TI  - Is there treatment for postpolio syndrome?

PMID- 7647621
TI  - Dermacase. Urticaria pigmentosa.

PMID- 7647622
TI  - Vaccine storage and handling. Knowledge and practice in primary care physicians'
      offices.
AB  - OBJECTIVE: To assess the knowledge and practice of vaccine storage and handling
      in primary care physicians' offices. DESIGN: A cross-sectional study was
      conducted from August to December 1992. Staff responsible for vaccine storage
      were interviewed about their knowledge and practices of vaccine handling and
      storage. Refrigerators were inspected to document refrigerator temperature and
      vaccine storage conditions. SETTING: General and pediatric practices in 12
      regions of Ontario. PARTICIPANTS: Practices outside metropolitan Toronto were
      selected by choosing every 10th physician who ordered vaccine from the local
      health department in 1992. Practices chosen in metropolitan Toronto were a random
      selection of physicians affiliated with a Toronto teaching hospital. Eighteen
      pediatric and 138 general practices were approached to participate; 12 pediatric
      and 123 general practices participated in the study. The overall response rate
      was 86.5%. MAIN OUTCOME MEASURES: Survey responses and temperature and storage
      conditions of refrigerators upon inspection. RESULTS: Fewer than seven (6%)
      practices answered all questions related to vaccine storage and handling
      correctly, and only 11 (10%) refrigerators had thermometers. One-third of
      refrigerators had temperatures outside the recommended range of 2 degrees C to 8
      degrees C. Older refrigerators were more likely to have inappropriate
      temperatures than newer ones. CONCLUSIONS: Knowledge and practice of vaccine
      storage and handling are often inadequate in primary care physicians' offices.

PMID- 7647623
TI  - Rural Alberta thrombolysis study. Survey of practice patterns for managing acute
      myocardial infarction.
AB  - OBJECTIVE: To determine current practice patterns for managing acute myocardial
      infarction in rural Alberta, particularly to examine the availability of
      thrombolytic therapy. DESIGN: Mailed questionnaire based on a clinical vignette.
      SETTING: All 104 acute care hospitals in rural Alberta with fewer than 100 beds.
      PARTICIPANTS: The Chief of Staff at each hospital. MAIN OUTCOME MEASURES:
      Proportion of hospitals providing thrombolytic therapy, choice of thrombolytic
      agent, rates of elective transfer after thrombolysis, and barriers preventing
      universal use of thrombolytic therapy. RESULTS: Questionnaires were completed by
      101 physicians. Three hospitals had no medical staff. Thrombolytic therapy was
      available in 80.8% of the hospitals. Hospitals that did not offer thrombolysis
      were smaller (average bed capacity 21.9 versus 37.7, P < 0.001), had fewer
      medical staff (average number 2.4 versus 5.5, P < 0.001), and had fewer nurses
      holding Advanced Cardiac Life Support certification (P = 0.015) than hospitals
      providing thrombolysis. Physicians identified inadequate nursing resources as the
      greatest barrier to providing thrombolysis. Of physicians using thrombolysis,
      71.4% chose streptokinase. Half of the physicians preferred elective transfer
      after the procedure. CONCLUSIONS: Thrombolytic therapy for acute myocardial
      infarction is standard practice in small hospitals in Alberta.

PMID- 7647625
TI  - New developments in hepatitis A control.
AB  - An inactivated vaccine for hepatitis A was recently licensed in Canada. This is
      the first important development in control of the disease in 50 years. This
      article presents new information about the vaccine and about the groups who might
      benefit from it. It also provides a review of the clinical and epidemiological
      aspects of hepatitis A.

PMID- 7647626
TI  - Grief counseling.
AB  - Patients grieve the loss of loved ones, jobs, marriages, or even functioning.
      They seek comfort, understanding, respect, and especially hope. The "work of
      grief" progresses through stages. Mixed with the sadness can be feelings of
      anger, fear, and guilt. Psychotherapy can relieve self-destructive anger and
      guilt, advance the recovery phase, and stimulate psychological strength and
      personality growth.

PMID- 7647624
TI  - Agriculture-related injuries in the parkland region of Manitoba.
AB  - OBJECTIVE: To review a series of farm injuries in the parkland region of
      Manitoba, compare the collected data to similar studies, and provide a baseline
      for deriving effective preventive measures for the local community. DESIGN:
      Retrospective case study involving review of hospital charts. SETTING: The
      population studied was derived from the catchment area for Dauphin General
      Hospital, a referral centre servicing an agricultural region of 57,000 people.
      PATIENTS: Seventy-two patients were admitted to hospital between January 1981 and
      December 1991 after being injured by agricultural machines, farm animals,
      herbicides or other chemicals, and fertilizers. Four fatalities were identified
      through a review of local medical examiner records, for a total of 76 cases. MAIN
      OUTCOME MEASURES: The following data were abstracted for each case: sex, age,
      time and date of injury, cause, type of injury, and body part involved. RESULTS:
      Most cases involved men, between the ages of 20 and 69, during the afternoon and
      early evening with a seasonal peak in late summer. More than 60% of injuries were
      caused by agricultural machinery, followed by animal-related injuries (25%).
      Grain augers were the most common type of machine causing injury (35%). All
      patients younger than 9 years were female, and 75% of their injuries involved
      farm animals. A decreasing annual frequency of farm injuries was noted over the
      11-year period. Fewer accidents involving farm machinery appear most responsible
      for this trend. CONCLUSIONS: Many agriculture-related injuries occur in the
      parkland region of Manitoba. The type and pattern of injuries observed resembles
      those documented in other studies. With effective education and preventive
      measures, most injuries and fatalities could be prevented. Physicians are obliged
      to encourage and support educational programs in their communities and to review
      safety practices with patients.

PMID- 7647627
TI  - Ankylosed spines are prone to fracture.
AB  - Fracture of an ankylosed spine is often overlooked. Because the force that
      damages an ankylosed spine is frequently slight, patients do not realize they are
      injured. Doctors can miss the fracture for the same reason and because patients
      already have a history of back pain. Plain radiographs sometimes fail to
      demonstrate the fracture site.

PMID- 7647628
TI  - National guidelines for vaccine storage and transportation. Laboratory Centre for
      Disease Control.

PMID- 7647629
TI  - Preventing hepatitis A infections. National Advisory Committee on Immunization
      statement. Laboratory Centre for Disease Control.

PMID- 7647630
TI  - Is there a cure for drug errors?

PMID- 7647631
TI  - Withdrawing artificial feeding from children with brain damage.

PMID- 7647632
TI  - Purified factor VIII.

PMID- 7647633
TI  - General practice at night.

PMID- 7647634
TI  - India hit by contaminated blood scandal.

PMID- 7647635
TI  - Report urges safety standards for dental anaesthesia.

PMID- 7647637
TI  - Study criticises protocols for labour.

PMID- 7647636
TI  - New York doctor guilty of murder in abortion death.

PMID- 7647638
TI  - WHO asks world court's opinion on nuclear weapons.

PMID- 7647639
TI  - Action against contraceptive implant threatened.

PMID- 7647640
TI  - Clinton aims to ban under age smoking.

PMID- 7647641
TI  - Cigarette smoking, tar yields, and non-fatal myocardial infarction: 14,000 cases
      and 32,000 controls in the United Kingdom. The International Studies of Infarct
      Survival (ISIS) Collaborators.
AB  - OBJECTIVES: To assess the effects of cigarette smoking on the incidence of non
      fatal myocardial infarction, and to compare tar in different types of
      manufactured cigarettes. METHODS: In the early 1990s responses to a postal
      questionnaire were obtained from 13,926 survivors of myocardial infarction
      (cases) recently discharged from hospitals in the United Kingdom and 32,389 of
      their relatives (controls). Blood had been obtained from cases soon after
      admission for the index myocardial infarction and was also sought from the
      controls. 4923 cases and 6880 controls were current smokers of manufactured
      cigarettes with known tar yields. Almost all tar yields were 7-9 or 12-15
      mg/cigarette (mean 7.5 mg for low tar (< 10 mg) and 13.3 for medium tar (> or =
      10 mg). The cited risk ratios were standardised for age and sex and compared
      myocardial infarction rates in current cigarette smokers with those in non
      smokers who had not smoked cigarettes regularly in the past 10 years. RESULTS: At
      ages 30-49 the rates of myocardial infarction in smokers were about five times
      those in non-smokers (as defined); at ages 50-59 they were three times those in
      non-smokers, and even at ages 60-79 they were twice as great as in non-smokers
      (risk ratio 6.3, 4.7, 3.1, 2.5, and 1.9 at 30-39, 40-49, 50-59, 60-69, 70-79
      respectively; each 2P < 0.00001). After standardisation for age, sex, and amount
      smoked, the rate of non-fatal myocardial infarction was 10.4% (SD 5.4) higher in
      medium tar than in low tar cigarette smokers (2P = 0.06). This percentage was not
      significantly greater at ages 30-59 (16.6% (7.1)) than at 60-79 (1.0% (8.5)). In
      both age ranges the difference in risk between cigarette smokers and non-smokers
      was much larger than the difference between one type of cigarette and another
      (risk ratio 3.39 and 3.95 at ages 30-59 for smokers of similar numbers of low and
      of medium tar cigarettes, and risk ratio 2.35 and 2.37 at ages 60-79). Most
      possible confounding factors that could be tested for were similar in low and
      medium tar users, with no significant differences in blood lipid or albumin
      concentrations. CONCLUSION: The present study indicates that the imminent change
      of tar yields in the European Union to comply with an upper limit of 12
      mg/cigarette will not increase (and may somewhat decrease) the incidence of
      myocardial infarction, unless they indirectly help perpetuate tobacco use. Even
      low tar cigarettes still greatly increase rates of myocardial infarction,
      however, especially among people in their 30s, 40s, and 50s, and far more risk is
      avoided by not smoking than by changing from one type of cigarette to another.

PMID- 7647642
TI  - A 28 year follow up of mortality among women who smoked during pregnancy.
AB  - OBJECTIVE: To investigate long term mortality among women who smoked during
      pregnancy and those who stopped smoking. DESIGN: A follow up of a geographically
      defined cohort from 1966 through to 1993. SUBJECTS: 11,994 women in northern
      Finland expected to deliver in 1966, comprising 96% of all women giving birth in
      the area during that year. Smoking habits were recorded during pregnancy but not
      later. MAIN OUTCOME MEASURE: Mortality by cause (571 deaths). RESULTS: The
      mortality ratio adjusted for age, place of residence, years of education and
      marital status was 2.3 (95% confidence interval 1.8 to 2.8) for the women who
      smoked during pregnancy and 1.6 (1.1 to 2.2) for those who stopped smoking before
      the second month of pregnancy, both compared with non-smokers. Among the smokers
      the relative mortality was higher for typical diseases related to tobacco intake,
      such as respiratory and oesophageal cancer and diseases of the cardiovascular and
      digestive organs and also for accidents and suicides. CONCLUSION: The risk of
      premature death seems to be higher in women who smoke during pregnancy than in
      other women who smoke. This may be explained either by the low proportion of
      those who stop later and the high proportion of heavy smokers or by other
      characteristics of these subjects that increase the risk.

PMID- 7647643
TI  - Non-specific beneficial effect of measles immunisation: analysis of mortality
      studies from developing countries.
AB  - OBJECTIVE: To examine whether the reduction in mortality after standard titre
      measles immunisation in developing countries can be explained simply by the
      prevention of acute measles and its long term consequences. DESIGN: An analysis
      of all studies comparing mortality of unimmunised children and children immunised
      with standard titre measles vaccine in developing countries. STUDIES: 10 cohort
      and two case-control studies from Bangladesh, Benin, Burundi, Guinea-Bissau,
      Haiti, Senegal, and Zaire. MAIN OUTCOME MEASURES: Protective efficacy of standard
      titre measles immunisation against all cause mortality. Extent to which
      difference in mortality between immunised and unimmunised children could be
      explained by prevention of measles disease. RESULTS: Protective efficacy against
      death after measles immunisation ranged from 30% to 86%. Efficacy was highest in
      the studies with short follow up and when children were immunised in infancy
      (range 44-100%). Vaccine efficacy against death was much greater than the
      proportion of deaths attributed to acute measles disease. In four studies from
      Guinea-Bissau, Senegal, and Burundi vaccine efficacy against death remained
      almost unchanged when cases of measles were excluded from the analysis.
      Diphtheria-tetanus-pertussis and polio vaccinations were not associated with
      reduction in mortality. CONCLUSION: These observations suggest that standard
      titre measles vaccine may confer a beneficial effect which is unrelated to the
      specific protection against measles disease.

PMID- 7647644
TI  - Absence of evidence is not evidence of absence.

PMID- 7647645
TI  - Rectal bleeding: prevalence and consultation behaviour.
AB  - OBJECTIVES: To determine prevalence of rectal bleeding in the community and to
      examine factors that lead some patients to consult their general practitioner
      about rectal bleeding while others do not. DESIGN: Questionnaire survey followed
      by semistructured interviews of sample of respondents with rectal bleeding.
      SETTING: Two general practices on Tyneside. SUBJECTS: 2000 adult patients
      registered with the general practices were sent a validated questionnaire.
      Respondents with rectal bleeding were divided into consulters and non-consulters,
      and 30 patients from each group (matched for age, sex, and characteristics of
      bleeding) were interviewed. MAIN OUTCOME MEASURES: Prevalence of rectal bleeding,
      proportion of subjects with rectal bleeding who sought medical advice, and
      reasons for consulting or not consulting a doctor about rectal bleeding. RESULTS:
      287 of the 1200 respondents to the questionnaire had noticed rectal bleeding at
      some time in their lives, and 231 had noticed it within previous 12 months. Only
      118 (41%) of all respondents with rectal bleeding had ever sought medical advice
      for the problem. Those aged over 60 were most likely to have consulted, as were
      those who reported blood mixed with their stools. Main difference between those
      who had sought medical advice and those who had not was that consulters were more
      likely than non-consulters to perceive their symptoms as serious. CONCLUSIONS:
      Although rectal bleeding is common, only minority of patients seek medical of
      symptoms seems to be most important factor in deciding whether to consult a
      doctor for rectal bleeding.

PMID- 7647646
TI  - Benign positional vertigo: recognition and treatment.

PMID- 7647647
TI  - The hard boiled saint: Selwyn-Clarke in Hong Kong.

PMID- 7647648
TI  - Raising the dead: war, reparation, and the politics of memory.
AB  - All societies attach a different range of meanings to war than to natural
      disasters, and questions of societal recognition, reparation, and justice are
      generally central. Most modern conflict has been grounded in the use of terror to
      control and silence whole populations. Those abusing power typically refuse to
      acknowledge their dead victims, as if they had never existed and were mere
      wraiths in the memories of those left behind. This denial, and the impunity of
      those who maintain it, must be challenged if survivors are to make sense of their
      losses and the social fabric is to mend. For the names and fate of the dead to be
      properly lodged in the public record of their times also illuminates the costs
      that may flow from the philosophies and practices of the Western led world order,
      ones which health workers should be in a position to influence.

PMID- 7647649
TI  - French Polynesia: a nuclear paradise in the Pacific.

PMID- 7647650
TI  - ABC of medical computing. Online searching.

PMID- 7647651
TI  - The death of biomedical journals. Electronic journals supplement their paper
      cousins.

PMID- 7647652
TI  - The death of biomedical journals. Permanence of paper puts authors on best
      behaviour.

PMID- 7647653
TI  - The death of biomedical journals. Popularity does not equal peer review.

PMID- 7647654
TI  - The death of biomedical journals. Journals are not yet obsolete.

PMID- 7647655
TI  - Management of cardiac arrest by ambulance technicians and paramedics. Paramedics
      have other uses beside attending cardiac arrests.

PMID- 7647656
TI  - Management of cardiac arrest by ambulance technicians and paramedics. Paramedics
      were not used effectively.

PMID- 7647657
TI  - Most consultants deviate from asthma guidelines.

PMID- 7647658
TI  - Management of cardiac arrest by ambulance technicians and paramedics. Benefit of
      paramedics in non-ventricular fibrillation arrests is transitory.

PMID- 7647659
TI  - Debriefing after psychological trauma. Inappropriate exporting of western culture
      may cause additional harm.

PMID- 7647660
TI  - Management of cardiac arrest by ambulance technicians and paramedics. Studying
      only admissions is a source of potential bias.

PMID- 7647661
TI  - Debriefing after psychological trauma. Response to stress is not necessarily
      pathological.

PMID- 7647662
TI  - Debriefing after psychological trauma. Response to treatment varies.

PMID- 7647663
TI  - Their lordships on medical research.

PMID- 7647664
TI  - Voluntary euthanasia commands majority support.

PMID- 7647665
TI  - Effects of homoeopathy. Trial did not evaluate "true" homoeopathy.

PMID- 7647666
TI  - Effects of homoeopathy. Trial puts negative gloss on essentially positive
      results.

PMID- 7647667
TI  - Spinal cord injury in Rugby Union players.

PMID- 7647668
TI  - Thyroid cancer in the United States since accident at Chernobyl.

PMID- 7647669
TI  - Training in family planning encompasses several disciplines.

PMID- 7647670
TI  - Calculating drug doses. Mass concentration can't be used universally.

PMID- 7647671
TI  - Calculating drug doses. Teaching of undergraduates must be improved.

PMID- 7647672
TI  - Provision of screening for Down's syndrome.

PMID- 7647673
TI  - Ongoing electronic conference is available for general practitioners.

PMID- 7647674
TI  - CD4 cell counts used as surrogate test for HIV infection.

PMID- 7647675
TI  - Effects of drinking green tea.

PMID- 7647676
TI  - Helping health services in the developing world.

PMID- 7647677
TI  - General practice's last stand.

PMID- 7647678
TI  - Misleading drug packaging.

PMID- 7647679
TI  - Pacific nuclear tests should not go ahead.

PMID- 7647680
TI  - Dipeptide transport in barley mesophyll vacuoles.
AB  - The transport of [14C]glycyl-glycine (Gly-Gly) across the tonoplast of isolated
      barley vacuoles has been characterized. Uptake of the dipeptide Gly-Gly into
      barley mesophyll vacuoles was strongly increased by the addition of ATP, while
      Mg2+ inhibited the ATP-dependent fluxes. Inhibition of the vacuolar proton pump
      by bafilomycin or dissipation of the delta pH had no effect on the ATP-dependent
      Gly-Gly uptake. Only the non-hydrolysable ATP analogue 5'
      adenylylimidodiphosphate could partially substitute for ATP; ADP, GTP and UTP had
      no effect. Transport of Gly-Gly was saturable exhibiting an apparent Km of 49 +/-
      5 mM. Uptake was inhibited by the sulphydryl reagents N-ethylmaleimide and p
      chloromercuribenzenesulphonic acid. When present at 30 mM, various dipeptides as
      well as tri-glycine inhibited Gly-Gly (10 mM) uptake by 30-50%, whereas 5 mM
      phenylalanine was able to inhibit Gly-Gly uptake almost completely. Comparison
      with published data suggests that Gly-Gly is transferred across the tonoplast by
      the same system as several amino acids and inorganic ions.

PMID- 7647681
TI  - The accumulation of a cold-regulated chloroplastic protein is light-dependent.
AB  - The protein encoded by cDNA clone pt59 and induced in barley (Hordeum vulgare L.)
      by cold was over-expressed in coli to produce the matching antibody, which in
      vivo recognized a cold-induced protein of 14 kDa (COR14) that was found in the
      chloroplast stroma. The accumulation of COR14 occurred only at low temperatures
      after even a brief exposure of the plants to light. Plants grown and fully
      hardened in the dark accumulated a reduced amount of pt59-corresponding mRNA and
      only traces of COR14. Light exposure for as short as 5 min was enough to
      normalize the expression of pt59-corresponding mRNA and increase the accumulation
      of COR14. These findings indicate that one or more light-dependent factors are
      involved in transcription of the gene and accumulation of the protein. The COR14
      protein was stored in amounts only slightly greater in the resistant barley
      cultivar. Onice than in the susceptible cultivar Gitane, although the former had
      a higher induction-temperature threshold for COR14 than the latter. This fact is
      an evolutionary advantage, enabling the resistant varieties in the field to
      prepare the cold well ahead of the susceptible ones.

PMID- 7647682
TI  - The maize brittle 1 gene encodes amyloplast membrane polypeptides.
AB  - A chimeric protein, formed of 56 amino acids from the carboxy terminus of the
      maize (Zea mays L.) wild-type Brittle1 (Bt1) protein fused to the glutathione-S
      transferase gene, was synthesized in Escherichia coli, and used to raise
      antibodies. Following affinity purification, the antibodies recognized a set of
      38- to 42-kDa proteins in endosperm from wild-type Bt1 plants, as well as from
      brittle2, shrunken2 and sugary1 plants, but not in mutant bt1 endosperm. Bt1
      proteins were not detected with the preimmune antibodies. A low level of Bt1
      specific proteins was detected at 10 d after pollination (DAP) and increased to a
      plateau at 16 DAP. At the same time, the ratio of slow- to fast-migrating forms
      of the protein decreased. During endosperm fractionation by differential
      centrifugation and membrane sedimentation in sucrose gradients, the Bt1 proteins
      co-purified with the carotenoid-containing plastid membranes. They were localized
      to amyloplasts by electron-microscopic immunocytochemistry; most of the signal
      was detected at the plastid periphery. These results are consistent with
      predictions made from the deduced amino-acid sequence and previous in-vitro
      experiments that the bt1 locus encodes amyloplast membrane proteins.

PMID- 7647683
TI  - Age-dependent induction of pyruvate, orthophosphate dikinase in Mesembryanthemum
      crystallinum L.
AB  - A full-length transcript for pyruvate, orthophosphate dikinase (PPDK; EC
      2.7.9.1), has been characterized from Mesembryanthemum crystallinum. Under salt
      stress or with increasing age, this plant shows a transition from C3 to
      Crassulacean acid metabolism (CAM). The PPDK plays a central role in
      gluconeogenesis during the light phase of CAM. The transcript is 3165 bases in
      length with a single open reading frame of 2739 nucleotides specifying a protein
      of molecular mass 103098, including a transit peptide of mass 7902 for
      chloroplast import. The protein shares 44-77% sequence identity with PPDK from C4
      plants and microorganisms. Known functional and regulatory amino acids are
      conserved. Southern-type hybridizations indicated one copy or very few closely
      related copies of the gene per haploid genome. We investigated the induction of
      PPDK at the mRNA and protein levels, using the well characterized induction of a
      CAM-form of phosphoenol pyruvate carboxylase (PEPCase) as internal standard.
      During wilting of excised leaves PEPCase mRNA amounts increased strongly within 8
      h. Under these conditions amounts of PPDK mRNA remained constant. Re-hydrating
      leaves from previously stressed plants led to a decrease in PEPCase and PPDK mRNA
      amounts. During salt stress, no correlation between PEPCase and PPDK was
      observed. Analysis of plants of different ages indicated that, even in well
      watered plants, PPDK-specific protein and mRNA increased when the plants reached
      a certain age. In old plants, salt stress failed to further increase PPDK mRNA or
      protein levels.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7647684
TI  - The characterisation of tapetum-specific cDNAs isolated from a Lilium henryi L.
      meiocyte subtractive cDNA library.
AB  - Differential screening of a meiocyte subtractive cDNA library from Lilium henryi
      L. has identified a group of 16 anther-specific partial cDNAs. Three of these
      sequences, LHM2, LHM6 and LHM7 have been further characterised. Hybridisation in
      situ with antisense riboprobes of LHM2, LHM6, and LHM7 gives a strong, clear
      signal which, contrary to expectations, is localised to the tapetal layer
      surrounding the meiocytes and not the meiocytes themselves. Developmental slot
      blots demonstrate that mRNAs corresponding to the three LHM cDNAs are transcribed
      from prophase of meiosis I to the uninucleate microspore stage, while Northern
      analysis reveals these tapetally expressed cDNAs to correspond with transcripts
      of some 500 bp. Although LHM2 is less abundant than LHM6 and LHM7, the pattern of
      developmental expression, and the size range of the transcripts suggests that all
      three cDNAs may be related. The deduced polypeptide products of LHM6 and LHM7
      share 71% identity over a conserved region of 38 residues. Inverse polymerase
      chain reaction was used to obtain the full sequence for LHM7. Its deduced protein
      sequence has a signal peptide indicating it may be secreted; the cleaved protein
      has a molecular weight of 8.9 kDa. Furthermore, the LHM7 protein has significant
      levels of homology with tapetally expressed proteins from Arabidopsis thaliana,
      Antirrhinum majus and Lycopersicon esculentum. All contain a highly conserved
      pattern of cysteine residues present in seed and non-specific lipid transfer
      proteins. The function of this gene product is discussed in the perspective of
      current models of another development.

PMID- 7647685
TI  - The promoter of the Arabidopsis thaliana SUC2 sucrose-H+ symporter gene directs
      expression of beta-glucuronidase to the phloem: evidence for phloem loading and
      unloading by SUC2.
AB  - The Arabidopsis thaliana (L.) Heynh. SUC2 gene encodes a plasma-membrane sucrose
      H+ symporter. The DNA sequence of the SUC2 promoter has been determined. Using a
      translational fusion of this promoter to the N-terminus of beta-glucuronidase
      (GUS) and the GUS histochemical assay, the tissue specificity of the SUC2
      promoter was studied in Arabidopsis plants transformed with this fusion
      construct. The SUC2 promoter directed expression of GUS activity with high
      specificity to the phloem of all green tissues of Arabidopsis such as rosette
      leaves, stems, and sepals. During leaf development the expression of SUC2-GUS
      activity was first seen in the tips of young rosette leaves. In older leaves and
      during their concomitant sink/source transition, expression proceeded from the
      tips to the bases of the leaves, indicating that expression of the SUC2 sucrose
      H+ symporter is tightly coupled to the source-strength of Arabidopsis leaves.
      Expression of SUC2-GUS activity was also seen, however, in sink tissues such as
      roots and developing Arabidopsis pods, suggesting that the product of the SUC2
      gene might not only be important for phloem loading, but also for phloem
      unloading. A possible regulatory effect of carbohydrates (glucose and sucrose) on
      the activity of the SUC2 promoter was studied and excluded, both in excised
      leaves and young seedlings of transgenic Arabidopsis plants. The overall pattern
      of SUC2-GUS expression correlated well with that of the Arabidopsis thaliana AHA3
      plasma-membrane H(+)-ATPase which is also expressed in the phloem and most likely
      represents the primary pump generating the energy for secondary active
      transporters such as SUC2.

PMID- 7647686
TI  - Degradation of transport-competent destabilized phaseolin with a signal for
      retention in the endoplasmic reticulum occurs in the vacuole.
AB  - To understand how plant cells exert quality control over the proteins that pass
      through the secretory system we examined the transport and accumulation of the
      bean (Phaseolus vulgaris L.) vacuolar storage protein phaseolin, structurally
      modified to contain a helix-breaking epitope and carboxyterminal HDEL, an
      endoplasmic reticulum (ER)-retention signal. The constructs were expressed in
      tobacco (Nicotiana tabacum L.) with a seed-specific promoter. The results show
      that phaseolin-HDEL accumulates in the protein-storage vacuoles, indicating that
      HEDL does not contain sufficient information for retention in the ER. However,
      the ER of seeds expressing the phaseolin-HDEL construct contain relatively more
      phaseolin-HDEL compared to phaseolin in the ER of seeds expressing the phaseolin
      construct. This result indicates that the flow out of the ER is retarded but not
      arrested by the presence of HDEL. Introduction into phaseolin of the epitope
      "himet" (Hoffman et al., 1988, Plant Mol. Biol. 11, 717-729) greatly reduces the
      accumulation of HiMet phaseolin compared to normal phaseolin. However, the
      increased abundance within the ER is similar for both phaseolin-HDEL and HiMet
      phaseolin-HDEL. Using immunocytochemistry with specific antibodies, HiMet
      phaseolin was found in the ER, the Golgi stack, and in transport vesicles
      indicating that it was transport competent. It was also present at an early stage
      of seed development in the protein-storage vacuoles, but was not found there at
      later stages of seed development. Together these results support the conclusion
      that the HiMet epitope did not alter the structure of the protein sufficiently to
      make it transport incompetent.

PMID- 7647688
TI  - Carcinogenic potential of human immunodeficiency virus (HIV): emerging evidence.

PMID- 7647687
TI  - Unusual sequence and characteristics of a chick-pea seed protein which is
      regulated by abscisic acid and is similar to late-embryogenesis-abundant
      proteins.
AB  - The cDNA clone GAB-9 was selected from a cDNA gene library constructed from the
      mRNA of embryonic axes of chick-pea (Cicer arietinum L.) seeds imbibed for 12 h
      in the presence of abscisic acid. The sequence of this cDNA has an open reading
      frame of 546 nucleotides that code for 182 amino acids. The polypeptide encoded
      by the corresponding mRNA is of approx. 20.5 kDa, is basic, and has a broad
      hydrophobic central region flanked by two hydrophilic regions. The unusual
      characteristics of this protein, which is similar to late-embryogenesis-abundant
      proteins, and its possible function are discussed.

PMID- 7647689
TI  - Effectiveness of beta-carotene in cancer chemoprevention.
AB  - This article reviews the current knowledge on the cancer-preventive potential of
      beta-carotene, a precursor of vitamin A, and plentiful in fruits and vegetables,
      which has been studied widely as a promising chemopreventive agent in reducing
      the risk of cancer in humans. Several retrospective and prospective
      epidemiological investigations have demonstrated that a diet rich in
      micronutrients such as vitamins, carotenoids and selenium, could prevent the
      arising, in 'high-risk' patients, of precancerous and neoplastic lesions of
      specific sites, particularly of the upper aerodigestive tract. Numerous in vitro
      expressions have been performed in order to verify the true role played by this
      agent on cell proliferation and differentiation; until now, findings have been
      very encouraging, uniformly showing the beta-carotene can affect carcinogenesis,
      particularly in early stages, through an antigenotoxic action. Antioxidant
      functions, immunomodulatory effects and control of intercellular messages via gap
      junctions are possible action mechanisms of the ability of beta-carotene to block
      the carcinogenetic process. In vivo animal studies partially confirm the results
      obtained in vitro showing that beta-carotene is able to reduce the induce cancer
      development; moreover, the association of the carotenoid with other
      microelements, such as vitamins E, C and glutathione often appears to be more
      effective than each agent used alone. From a clinical point of view, beta
      carotene appears an 'ideal' agent to be used in chemoprevention trials in humans,
      although optimal doses and intake methods need to be better defined; its almost
      zero toxicity permits the long-term administration of the drug, a vital condition
      for its anti-cancer activity, with good patient compliance. Human intervention
      studies performed so far, both randomized and uncontrolled clinical trials, have
      showed positive findings in specific cancer sites such as oral cavity, head and
      neck and colon; less consistent or negative are results on skin, lung and
      oesophagus cancer. The ongoing studies will provide more answer on these issues.
      A definitive evaluation of the ability of beta-carotene to prevent cancer in
      human requires further controlled trials; studies on a larger spectrum of cancer
      sites and different stages of disease must be encouraged. In addition, further
      investigation on biomarkers related to cancer risk and cancer incidence are
      necessary, particularly focused on the measurements for genotoxic damage, eg
      micronuclei, that may provide a valid and 'easy' marker for early stage
      carcinogenesis.

PMID- 7647690
TI  - Adipose tissue concentrations of dioxins and dibenzofurans in patients with
      malignant lymphoproliferative diseases and in patients without a malignant
      disease.
AB  - Concentrations of dioxins (PCDD) and dibenzofurans (PCDF) were analysed in
      adipose tissue from seven patients with malignant lymphoproliferative diseases
      and 12 surgical patients without a malignant disease. All cases in the first
      group had reported potential exposure to PCDD and PCDF. Of the analysed congeners
      significantly higher concentrations of 1,2,3,7,8-pentachlorodioxin, 1,2,3,6,7,8
      hexachlorodioxin, and 2,3,4,7,8-pentachlorodibenzofuran were found in the cases
      with lymphoproliferative diseases compared with the patients in the other group.
      Higher mean concentration of 2,3,7,8-TCDD was also found in the first group but
      not significantly so. Toxic equivalents of PCDD and PCDF were significantly
      higher in the first group (mean 64.7 pg/g, range 19.9-187) than in the second
      group (mean 29.7 pg/g, range 12.9-53.4). Even if the cases with
      lymphoproliferative diseases in this case series were potentially exposed to
      PCDD/PCDF in contrast to the other group, the observed differences may be of may
      be of interest in relation to the aetiology of these malignancies.
      Immunosuppression increases the risk for malignant lymphoproliferative diseases,
      and PCDD/PCDF have established immunotoxic properties.

PMID- 7647692
TI  - Dietary factors and colorectal polyps: a case-control study.
AB  - In the case-control study we compared dietary habits among 108 patients with
      small (< or = 5 mm, n = 26), medium (5-9 mm, n = 48) or large (> or = 10 mm, n =
      34) colorectal polyps with 35 healthy age- and gender-matched controls. A food
      record by weighing during 5 consecutive days was performed. The intake of fat was
      significantly higher among the patients, in contrast to a significantly lower
      intake of carbohydrate, dietary fibre and iron, compared with controls. The
      intake of vitamin C and calcium was shown to be lower among the patients, but
      this was significant only for women. There was a tendency among the patients to
      consume a lower-antioxidant, fibre and cereal fibre diet, and a calcium-rich and
      more cholesterol-rich diet with increasing size of polyps. The patients with the
      smallest polyps tended to consume less starch. Our results are too preliminary to
      draw conclusions with regard to the influence of nutritional factors on the size
      and growth of polyps. However, our risk factors for the presence of polyps are in
      agreement with previous studies. Further studies taking into account the size of
      the polyp are needed to corroborate our findings.

PMID- 7647691
TI  - Missing anti-proliferative effect of fish oil on rectal epithelium in healthy
      volunteers consuming a high-fat diet: potential role of the n-3:n-6 fatty acid
      ratio.
AB  - Several studies have indicated dietary fish oil (FO) as a protective agent in
      colon carcinogenesis. Rectal cell proliferation as an intermediate biomarker of
      cancer risk was shown to be reduced by dietary FO in patients with adenomatous
      polyps and healthy subjects consuming a low-fat diet. Because the synthesis of
      prostaglandins (PG) which seem to be involved in this process is dependent on the
      ratio of n-3:n-6 fatty acids in the diet, the present study was designed to
      investigate whether this FO effect is also detectable in volunteers eating a high
      fat diet (50% of energy) with a low n-3:n-6 ratio of 0.25. Twelve healthy
      volunteers received in addition to a controlled basal diet either FO (4.4 g n-3
      fatty acids/day) or corn oil supplements (double-blind, crossover) for two 4-week
      periods. No significant differences between the two study periods were found for
      rectal cell proliferation as assessed by bromodeoxyuridine immunohistochemistry
      and ornithine decarboxylase activity, as well as for mucosal PGE2 release and
      mucosal membrane fatty acid composition. The results emphasize the importance of
      dietary n-3:n-6 ratio in determining the effects of FO on rectal cell
      proliferation.

PMID- 7647693
TI  - Analysis of calcium-lipid complexes in faeces.
AB  - Calcium is purported to prevent colorectal cancer by forming insoluble complexes
      with bile acids and long-chain fatty acids in the large bowel. Therefore, a
      method for analysing calcium-lipid complexes in faeces has been developed to
      investigate this. The calcium soaps of a long-chain fatty acid (calcium
      palmitate) and bile acids (calcium deoxycholate, chenodeoxycholate, cholate and
      lithocholate) were obtained by organic synthesis. Studies with the authentic
      soaps reveal that they exist in an empirical ratio of calcium-to-lipid of 1:2. On
      addition to lipid-free faeces, approximately 30% of calcium palmitate could be
      recovered and quantified in the authentic state by extraction with 72% ethanol
      and overnight precipitation at 0 degree C. In contrast, the calcium soaps of the
      bile acids could not be recovered in the authentic state but were quantified
      entirely as the free acids. The method was applied to the analyses of calcium
      lipid complexes in the faeces of adenoma patients partaking in a placebo
      controlled calcium-intervention study. The results show that human faeces contain
      appreciable amounts of calcium long-chain fatty acid soaps predominantly in the
      form of calcium palmitate and stearate. The faecal concentration of long-chain
      fatty acid soaps was increased significantly (P = 0.005) during calcium
      intervention but this did not have a statistically significant effect on the
      excretion of free long-chain fatty acids (P = 0.4). Calcium long-chain fatty acid
      soap formation was found by multiple regression to be equally dependent on stool
      long-chain fatty acid and calcium concentration. Calcium soaps of the bile acids
      were not detected by this method.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7647694
TI  - UICC XVI International Cancer Congress New Delhi, India, 30 October to 5 November
      1994.

PMID- 7647695
TI  - Problem of perception and denial of illness by women who have had breast cancer.

PMID- 7647696
TI  - Mu-, delta-, kappa-opioid receptors and their subtypes. A critical review with
      emphasis on radioligand binding experiments.
AB  - Since the early 1970's, when specific binding sites for opiates were first
      described, there has been a vast literature on opiate receptors, their subtypes,
      and even the multiplicity of these subtypes. In the present review, the signal
      transduction pathways, structure, and brain and spinal cord localization of the
      established subtypes (mu, delta, kappa) are reviewed. In addition, evidence
      suggesting heterogeneity of these subtypes, in particular from radioligand
      binding studies, is discussed critically.

PMID- 7647697
TI  - Opioid receptors and their subtypes: focus on peripheral isolated tissue
      preparations.

PMID- 7647698
TI  - Functional studies on opioid receptor heterogeneity in the central nervous
      system.

PMID- 7647699
TI  - Novel functions for subtypes of metabotropic glutamate receptors.
AB  - Metabotropic or "G-protein coupled" glutamate receptors (mGluRs) were discovered
      and established as a new type of excitatory amino acid receptor by their unique
      coupling mechanism (phosphoinositide hydrolysis) and pharmacological
      characteristics. Recently, the cloning of mGluRs and the availability of
      selective pharmacological agents has greatly increased knowledge of these
      receptors. It is now recognized that mGluRs are a highly heterogenous family of
      glutamate receptors with novel molecular structure that are linked to multiple
      second messenger pathways. Members of this family have unique pharmacological
      properties and function to modulate the presynaptic release of glutamate and the
      post-synaptic sensitivity of the cell to glutamate excitation. New information on
      mGluRs is elucidating the functions of mGluR subtypes in normal and pathological
      aspects of neuronal transmission. Basic knowledge of the role of specific mGluRs
      in CNS function and pathologies will further expand in the near future. This
      knowledge is providing the framework for the discovery of novel pharmacological
      approaches to modulate excitatory amino acid neuronal transmission.

PMID- 7647700
TI  - The function of metabotropic excitatory amino acid receptors in synaptic
      transmission in the thalamus: studies with novel phenylglycine antagonists.
AB  - The phenylglycines 3-hydroxyphenylglycine, 4-carboxy-3-hydroxy-phenylglycine
      (4C3HPG), 4-carboxyphenylglycine (4CPG) and alpha-methyl-4-carboxyphenylglycine
      (MCPG) were evaluated as putative selective antagonists of metabotropic glutamate
      receptors on single neurones of the ventrobasal thalamus of rats, with a view to
      using these compounds as tools to elucidate synaptic mechanisms in this brain
      area. The S-isomers of the latter three compounds were found to reduce
      excitations evoked by iontophoretically applied 1S,3R-ACPD, but not those evoked
      by ionotropic excitatory amino receptor agonists. When the antagonists were
      tested against sensory synaptic responses of ventrobasal neurones, it was found
      that responses evoked by noxious thermal stimulation of the peripheral receptive
      field were reduced in parallel with responses to 1S,3R-ACPD. In contrast,
      responses of neurones evoked by non-noxious (air-jet) stimuli were not reduced by
      the phenylglycine antagonists and 4C3HPG was found to enhance such responses,
      possibly by a presynaptic action mediated via mGluR2 receptors. The reductions of
      nociceptive responses are discussed in the context of antagonism of mGluR1
      receptors, which are known to be numerous in the thalamus and located on post
      synaptic dendrites. The involvement of such receptors in the nociceptive
      responses of thalamic neurones may be of considerable functional significance.

PMID- 7647701
TI  - NMR spectroscopic study of cell cultures of astrocytes and neurons exposed to
      hypoxia: compartmentation of astrocyte metabolism.
AB  - Primary cultures of murine cerebral cortical astrocytes or cerebellar granule
      neurons were exposed to 7 h of hypoxia (3 h in some cases). The culture medium
      was analyzed at the end of the hypoxic or normoxic period by 1H NMR spectroscopy
      and intracellular components were analyzed as perchloric acid extracts by 31P and
      1H NMR spectroscopy. Lactate production in astrocytes increased only marginally,
      whereas high energy phosphate concentrations were reduced, during 7 h of hypoxia
      and after 17 h of reoxygenation. After 3 h of hypoxia full recovery was possible
      during reoxygenation. Citrate and glutamine secretion was reduced or unchanged,
      respectively, during 7 h of hypoxia. Succinate secretion was only observed during
      normoxia, whereas pyruvate was secreted during hypoxia. Cerebellar granule
      neurons were more efficient in increasing glycolysis and were, therefore, more
      resistant to the effects of hypoxia than astrocytes. In the neurons lactate
      production was doubled and no effects on levels of high energy phosphates were
      seen after 7 h of hypoxia. Astrocytes were reoxygenated for 17 h after hypoxia or
      normoxia in a medium containing [2-13C]acetate in order to access if astrocytes
      were still capable of supplying neurons with essential precursors. The media were
      subsequently analyzed by 13C NMR spectroscopy. After shorter periods of hypoxia
      (3 h) full recovery was possible. Citrate and glutamine production remained
      however decreased during reoxygenation after 7 h of hypoxia. 13C incorporation
      into glutamine was greatly reduced but that into citrate was unchanged. These
      results suggest that under the present conditions, neurons are more efficient
      than astrocytes in switching the energy metabolism from aerobic to anaerobic
      glycolysis and that astrocytes may suffer long term damage to mitochondria from
      longer periods of hypoxia. Furthermore, evidence is presented for the existence
      of several TCA cycles within astrocytes based on labeling ratios. During normoxia
      the labeling ratios in the C-2/C-4 positions in glutamine and in the equivalent
      positions in citrate were 0.27 and 0.11, respectively.

PMID- 7647702
TI  - Cytotoxic effects of glutamic acid on PC12 cells.
AB  - In order to investigate the biochemical mechanisms responsible for glutamate
      induced cell death, we have tested the effect of this excitatory amino acid on
      the growth and survival of several cell lines of neural origin. Most of the cell
      lines studied were insensitive to glutamate, but we observed in PC12 cells that
      addition of glutamate (1-10 mmol/l) led to a dose-dependent cell damage (70% of
      cell lysis at 10 mmol/l as estimated by lactate dehydrogenase release). This
      effect which was not due to an inhibition of cell proliferation was only obvious
      after 8-10 h of incubation and required the continuous presence of glutamate for
      at least 4-6 h, to become apparent. Studies of the cytotoxic effect of several
      glutamate analogues showed that neither N-methyl-D-aspartate nor kainate,
      ibotenate, trans(+/-) 1-amino 1,3-cyclopentane dicarboxylic acid or alpha-amino-3
      hydroxy-5-methyl isoxazole-4-propionic acid exerted any significant action and
      that quisqualate only was more potent than glutamate itself. A known antagonist
      of non-NMDA receptors, the 6,7-dinitroquinoxaline-2,3-dione, was able to
      significantly decrease the glutamate and quisqualate-induced cell lysis. In
      addition, we observed that glutamate effect was associated with a significant
      increase in arachidonate liberation from prelabelled cells.

PMID- 7647703
TI  - Encapsulated genetically engineered fibroblasts: release of nerve growth factor
      and effects in vivo on recovery of cholinergic markers after devascularizing
      cortical lesions.
AB  - Genetically engineered rat fibroblasts producing nerve growth factor (NGF) were
      encapsulated in alginate-polylysine-alginate gels with the objective to produce
      viable "minifactories" continuously producing and secreting NGF into the rat
      brain. Microencapsulated fibroblasts (NGF secretors and NGF non-secretors) were
      placed onto the surface of the lesioned rat cortex (unilateral devascularizing
      lesion) and animals were sacrificed 30 days after surgery. Fibroblasts NGF-non
      secreters normally produce tumors after implantation, therefore, they were
      irradiated prior to encapsulation. Three other experimental groups were studied
      in parallel: non-lesioned (controls), lesioned rats receiving "empty" alginate
      spheres and lesioned animals without treatment and microspheres. Biochemical
      analysis of microdissected brain tissues of lesioned animals treated with
      encapsulated NGF-secretor fibroblasts showed a significant increase in choline
      acetyltransferase (ChAT) activity in cortices adjacent to the lesion but not far
      from it (entorhinal cortex). This may indicate a gradient of concentration of the
      released NGF and/or differential responsivity of lesioned vs non-lesioned target
      tissue. ChAT enzymatic activity in the microdissected nucleus basalis
      magnocellularis (NBM) was significantly decreased (P < 0.05) in all lesioned
      animals treated with spheres without fibroblasts and those with fibroblasts not
      secreting NGF. Morphometric analysis of ChAT-IR and low affinity NGF-receptor IR
      cholinergic neurons in the middle portion of the NBM shows a prevention of
      neuronal shrinkage and extensive neuropil in animals treated with
      microencapsulated NGF-secretor fibroblasts. The results of this study demonstrate
      that NGF from encapsulated genetically engineered fibroblasts can be secreted for
      at least long enough to prevent degenerative changes of cholinergic neurons in
      the NBM.

PMID- 7647704
TI  - The protein composition of Friend cell nuclear matrix stabilized by various
      treatments. Different recovery of nucleolar proteins B23 and C23 and nuclear
      lamins.
AB  - Using two-dimensional polyacrylamide gels stained with Coomassie blue we have
      studied the protein composition of the nuclear matrix obtained from mouse
      erythroleukemic nuclei kept at 0 degrees C throughout the isolation procedure to
      prepare the high ionic strength resistant fraction (control matrix) or stabilized
      in vitro or in vivo by different procedures prior to subfractionation (ie 37
      degrees C incubation of isolated nuclei; sodium tetrathionate exposure of
      purified nuclei; heat shock of intact cells). When the matrix obtained from 37
      degrees C incubated nuclei was compared with the control matrix, striking
      differences in the polypeptide pattern were seen if the protein was obtained in
      both cases from an equivalent number of nuclei. On the other hand, if the same
      amount of protein for both the samples was applied to the gels the differences
      were less evident. Sodium tetrathionate stabilization of isolated nuclei and heat
      shock of intact cells produced a matrix protein pattern that was very similar and
      differed from that of the in vitro heat-exposed matrix. Using specific polyclonal
      antisera, we demonstrate that nucleolar proteins B23/numatrin and C23/nucleolin
      were very abundant in the matrix obtained from chemically-treated nuclei or in
      vivo heat-stabilized nuclei but were recovered in very small amounts (B23) or
      completely absent (C23) in the matrix prepared from nuclei heated to 37 degrees C
      in vitro. Differences were seen also in the recovery of nuclear lamins, and
      especially lamin B, that was poorly represented in the sodium tetrathionate
      stabilized matrix. The results demonstrate that in mouse erythroleukemia cells
      the increased recovery of nuclear matrix protein that is seen after in vitro
      heating of isolated nuclei is predominantly due to an additional recovery of the
      same types of polypeptides that are detected also in the absence of such a
      treatment. The data also indicate that in vivo heat shock of intact cells
      produces a nuclear matrix protein pattern that is more similar to the pattern
      seen after stabilization of purified nuclei with sodium tetrathionate and differs
      significantly from that obtained by exposing nuclei to 37 degrees C in vitro,
      unlike to that what previous reports have indicated.

PMID- 7647705
TI  - Partial amino acid sequence and functional aspects of histone H1 proteins in
      Trypanosoma brucei brucei.
AB  - Trypanosoma brucei brucei, a protozoan parasite of wild and domestic animals in
      Africa, is related to the pathogenic agent of human sleeping sickness. Four H1
      histone proteins were isolated from nuclei of procyclic culture forms and cleaved
      with proteases. Amino acid sequence analysis of purified fragments indicated the
      presence of variants which displayed sequence identities as compared to the C
      terminal domain of human H1. Substitutions of amino acids and posttranslational
      modifications of the histones in T b brucei H1 may influence protein conformation
      and histone-histone as well as histone-DNA interactions in the chromatin of the
      parasite. Digestion of soluble chromatin with immobilized trypsin at low and high
      ionic strengths indicated an internal localization of H1 in the condensed
      chromatin. The influence of histone H1 of T b brucei on the compaction pattern of
      the chromatin was investigated by dissociation and reconstitution experiments.
      Electron microscopy revealed that trypanosome H1 was able to induce condensation
      of the chromatin of the parasite and of rat liver into dense tangles. After
      dephosphorylation of H1, 30 nm fibers were induced in rat liver chromatin, while
      the resulting fibers were distinctly thinner in T b brucei. It can be concluded
      that the absence of 30 nm fibers in T b brucei chromatin cannot be explained by
      the divergent variants and posttranslational phosphorylations of H1 only but
      rather by the influence of both, the divergent core histones, previously
      described, and H1 properties.

PMID- 7647706
TI  - Study of human erythrocyte membrane protein interactions by selective
      solubilization of Triton-skeletons.
AB  - The membrane skeleton, responsible for shape and mechanical properties of the red
      cell, was purified by the Triton extraction procedure in presence of 5 mM, 150 mM
      or 600 mM NaCl. The proportion of spectrin, protein 4.1 and actin present in
      erythrocyte skeletons does not depend on the molarity of NaCl used. In contrast
      ankyrin, protein band 3 and protein 4.2 are removed from skeletons as the ionic
      strength increased. Solubilization assays of membrane skeletons were used to
      study protein interactions inside the skeleton. Solubilization was performed by
      Tris, a non-selective disruptive reagent, or by p-mercuribenzene sulfonic acid
      (PMBS), which principally release spectrin and actin. Tris action was assessed by
      calculation of the percentage of solubilized proteins, which increased
      proportionally with Tris molarity. PMBS action was kinetically determined as the
      decrease in skeleton turbidity. With these two reagents, we observed a lower
      dissociation of skeletons prepared with high ionic strength buffer. Erythrocyte
      pretreatment with okadaic acid, an inhibitor of serine-threonine phosphatases,
      revealed a phosphorylation-induced skeleton gelation and a better resistance to
      Tris-solubilization.

PMID- 7647707
TI  - Distribution of actin microfilaments in frog skin epithelial granular cells.
AB  - Microfilaments were localised by immunofluorescence and immunogold cytochemistry
      to examine their distribution in granular cells of the isolated frog skin
      epithelium. Strongly fluorescent bundles of actin were observed beneath the
      plasma membrane with little evidence for actin in the central regions. Higher
      resolution offered by cytochemistry revealed that bundles of actin filaments
      comprised a substantial portion of the cortical cytoskeleton. Quantitative
      analysis of the frequency of gold label revealed an extremely rich array of
      filaments beneath the apical membrane of granular cells, with markedly less label
      along the basolateral membrane and in the central cytoplasm. Treating cells with
      cytochalasin B or arginine vasopressin caused an apparent disruption of the
      apical actin fibres, concurrent with a decrease in gold label density. Assumably
      these signs are indicative of depolymerization of the filaments. Although the
      significance of this distribution is unknown, the apical polarisation of actin is
      consistent with a role in regulating the Na+ permeability of the apical membrane.
      The data are discussed in relation to possible roles of the cytoskeleton in the
      regulation of transepithelial sodium transport by vasopressin.

PMID- 7647708
TI  - A simple cell labeling technique by means of lectins linked to fluorochromes for
      the detection of cells on tissue sections.
AB  - We designed a protocol for cell labeling with the lectin wheat germ agglutinin
      (WGA) linked to the fluorochrome tetramethyl-rhodamine isothiocyanate (TRITC) for
      effective detection of the B16F10 melanoma and Lewis lung carcinoma (LLc) cells
      on pulmonary histological sections from C57BL/6 mice. We have also determined a
      suitable concentration of WGA-TRITC (10 micrograms/ml), which leads to a very
      intense and homogeneous labeling of the cells, as it avoids cell clumping due to
      the presence of the lectin WGA. In order to determine to what extent the method
      affects these tumor cells, we have studied some important aspects related to
      their metastatic behavior, taking into account three parameters: a) viability and
      rate of proliferation of the cells cultured in vitro; b) percentage of animals
      (C57BL/6 mice) bearing metastasis 15 days after intravenous inoculation with
      10(5) B16F10 or LLc cells; and c) pattern of distribution of tumor foci in lung.
      There were no significant differences in these three parameters between the WGA
      TRITC labeled-cells compared to the cultures of non-labeled cells in either of
      the cell lines (B16F10, LLc). Thus, we conclude that B16F10 and LLc tumor cells
      can be labeled following the protocol set-up in our study, as it allows these
      cells to be neatly identified on tissue sections and it causes no important
      physiological changes in the cells, with regard to metastatic behavior. These
      points make this technique very suitable for the detection of B16F10 and LLc
      cells on histological sections in studying their behavior during the first stages
      of the metastatic process.

PMID- 7647709
TI  - Death and people with learning disabilities: interventions to support clients and
      carers.
AB  - The needs of people with learning disabilities who are bereaved have been
      acknowledged in the last decade. There is more understanding of ways to meet
      these needs. Carers need training and support when working with people who are
      dying or bereaved. This paper reviews the relevant literature, offers guidelines
      for practice and highlights areas for further development.

PMID- 7647710
TI  - The nature and long-term effects of childhood sexual abuse: a survey of adult
      women survivors in Britain.
AB  - The nature and long-term effects of childhood sexual abuse (CSA) were examined in
      775 women survivors who responded to a survey in a women's magazine. Compared to
      existing research, there was a high rate of CSA involving sexual intercourse
      (46%), a high rate of intra-familial abuse (80%), a younger age of onset of abuse
      (8.5 years), and a longer duration of abuse (5.2 years). In univariate analyses,
      the reporting of a range of long-term psychological effects was significantly
      related to experience of abuse involving sexual intercourse or sexual contact,
      abuse perpetrated by a father or stepfather, abuse which was repeated or
      prolonged, presence of threats or violence, blaming of the child, saying
      disclosure would split the family, and a younger age of onset. In logistic and
      multiple regression analyses, the most important predictor variables were
      presence of threats or violence, and verbal coercion, followed by abuse being
      repeated or prolonged. It is suggested that future researchers should use a range
      of assessment instruments and multivariate analyses to examine the nature and
      long-term effects of child sexual abuse in both women and men.

PMID- 7647711
TI  - Further evidence for a multidimensional personality disposition to schizophrenia
      in terms of cognitive inhibition.
AB  - A study is reported using the 'negative priming' paradigm to examine individual
      differences in cognitive inhibition in relation to distinct features of
      schizotypy. Seventy psychology students completed four measures of schizotypy,
      selected to index specific schizotypal traits: the Schizotypy Scale (STA), the
      Magical Ideation (MI) Scale, the Revised Social Anhedonia (SoA) Scale and the
      Physical Anhedonia (PhA) Scale. The priming paradigm was based on that of Beech,
      McManus, Baylis & Agar (1991), including conventional repeat and semantic priming
      conditions as well as repeat and semantic negative priming conditions, but
      differed in terms of task and stimuli. Cluster analysis of STA scores revealed a
      four-cluster solution reflecting 'very low', 'moderately low', 'moderately high'
      and 'very high' STA scores. Cluster analysis of MI, SoA, and PhA Scale scores
      also revealed four clusters. The first cluster comprised those with low scores on
      all scales. The remaining three clusters were distinguished by those with high
      MI, high SoA, and high PhA Scale scores, respectively. Those with high STA, MI,
      and SoA scale scores showed a significantly reduced, or reversed, repeat and
      semantic negative priming effect compared to those with moderately low STA scores
      and those low on all scales, respectively. An unexpected finding was that
      participants with high and moderately high STA scores as well as those with high
      MI and SoA scores revealed an inhibitory rather than facilitatory conventional
      repeat priming effect. It is concluded that weakening of inhibitory processes may
      be associated with a strong presence of schizotypal features related to
      dimensions of positive schizophrenic symptomatology, whereas schizotypal traits
      that parallel purely negative schizophrenic symptoms are not linked to reduced
      inhibition unless there is also a presence of 'positive' schizotypal features.
      The association of some schizotypal traits with an inhibitory repeat priming
      effect indicates that stimuli and task differences have a bearing on the
      attentional processes underlying priming effects for these participants. Thus,
      Beech et al.'s 'reduced-inhibition' model of schizophrenic symptomatology may
      require refinement.

PMID- 7647712
TI  - Clients' preferences for styles of therapy.
AB  - Clients' preferences for different styles of therapy were studied by showing
      videos depicting five different styles (psychodynamic, cognitive-behavioural,
      humanistic, external and naive) to psychiatric day hospital patients. After
      seeing each video, clients rated credibility, personal preference, and the depth
      and smoothness subscales of the Session Evaluation Questionnaire. Credibility and
      personal preference were highly correlated. Overall, clients had clear
      differential preferences between styles. The cognitive-behavioural style was
      preferred to other styles in all measures. There were only weak associations
      between individual difference variables and preferences.

PMID- 7647713
TI  - Cognitive estimation in neurological disorders.
AB  - The Cognitive Estimation Test (CET) was devised by Shallice & Evans (1978) in an
      attempt to quantify the tendency observed in some patients with frontal lobe
      lesions to produce bizarre estimates in response to questions to which people do
      not usually know exact answers (e.g. 'what is the height of a double-decker
      bus?'), despite performing normally on standard intelligence tests. In the
      present study, the CET performance of a large number of patients suffering from
      head injury, brain tumour, ruptured aneurysm (anterior communicating artery and
      other), multiple sclerosis, dementia, encephalitis, Korsakoff's syndrome and
      anxiety/depression were compared with CET scores from 150 healthy controls.
      Patients with Korsakoff syndrome demonstrated significantly impaired CET
      performance. A subgroup of patients with discrete frontal lesions was compared
      with a group with localized non-frontal lesions. No significant difference in CET
      performance was observed between anterior and posterior lesioned patients. The
      sensitivity of the CET to anterior brain dysfunction is called into question by
      the present findings.

PMID- 7647714
TI  - The importance of the first three days: predictors of treatment outcome in
      depressed in-patients.
AB  - This study investigated whether initial reactions, as shown by depressed patients
      and by the psychiatrist in charge within the first three days of complex hospital
      treatment, predicted outcome. Sixty-three patients with depressive disorders
      according to ICD-10 were examined. In addition to basic socio-demographic and
      clinical data and to baseline symptoms, psychiatrists' optimism, patients' global
      assessment of treatment and symptom change within the first three days were
      tested as predictors. The outcome criteria were both observer and self-ratings of
      symptoms at discharge. Psychiatrists' optimism was the best single predictor of
      each outcome criterion. Patients' initial subjective reactions predicted self
      rated symptoms at discharge. In stepwise multiple regression analyses initial
      reactions contributed significantly and - in two cases - separately to the
      overall prediction of outcome. Patients' and psychiatrists' initial reactions in
      complex hospital treatment of depression are relatively good predictors of
      outcome and should, therefore, be monitored carefully in research and in clinical
      practice.

PMID- 7647715
TI  - The WAIS-R(UK): basic psychometric properties in an adult UK sample.
AB  - The WAIS-R is the most widely used measure of intellectual ability in the UK,
      despite never having been standardized in this country. The present study
      examined the psychometric properties of the WAIS-R in a sample of 200 subjects,
      which was representative of the adult UK population in terms of the distributions
      of age, sex and social class. The properties of the three IQ scales, i.e. the
      FSIQ, the VIQ and the PIQ, were found to be very similar to those reported for
      the US standardization sample: the scores were normally distributed, with means
      close to the desired value of 100; moreover, the reliabilities of the IQ scales
      were extremely high and closely matched the US reliabilities. There were also
      indications, however, that the scales have restricted standard deviations when
      used in the UK. The reliabilities of the 11 original subtests ranged from
      moderate to high and the majority were similar to the US reliabilities. However,
      in addition to evidence of restricted SDs, significant differences (sometimes as
      much as two-thirds of an SD) were found among the subtest means. These in-built
      subtest discrepancies could lead to erroneous conclusions about an individual's
      performance. A conversion table for UK test users is provided to overcome this
      problem.

PMID- 7647716
TI  - Modified Personal Questionnaire Rapid Scaling Technique for measuring delusional
      beliefs.
AB  - The view of delusions as discrete and discontinuous phenomena is changing.
      Intensity of conviction in delusional belief has been used as a dependent
      variable in therapeutic attempts at belief modification. It has been measured
      using rating scales and developments of Shapiro's Personal Questionnaire (PQ)
      technique. The use of Mulhall's Personal Questionnaire Rapid Scaling Technique
      (PQRST) has not been reported in this context. The paper reports no new clinical
      data but describes a modified PQRST for measuring intensity of belief conviction,
      suitable for clients who cannot understand the PQ technique and easily
      administered by ward staff.

PMID- 7647717
TI  - Autobiographical memory and chronic pain.
AB  - The influence of chronic pain on the recall of autobiographical memories of pain
      and non-pain events was examined. Eleven chronic pain patients and 11 age- and
      sex-matched control subjects retrieved autobiographical memories to neutral and
      pain-related cue words. Patients and controls retrieved equal numbers of
      memories, but pain subjects retrieved more memories incorporating elements of
      physical pain. Analysis of the content of these memories revealed that patients
      and controls recalled equal numbers of memories of themselves and other people in
      acute pain and that the difference observed was attributable to the pain patients
      recalling memories of themselves in chronic pain. Memories of pain were recalled
      significantly faster than non-pain memories. The results are discussed with
      reference to the possible biasing effects of pain state on memory and the
      schematic processing of pain memories.

PMID- 7647718
TI  - Endorsement and memory bias of self-referential pain stimuli in depressed pain
      patients.
AB  - This study investigates information processing in chronic pain patients by
      comparing the responses of depressed pain patients, non-depressed pain patients
      and non-pain control subjects. Each subject contributed two scores: endorsement
      of adjectives as descriptors of themselves and their best-friends; and free
      recall of the presented words. The stimuli consisted of depression-related, pain
      related and neutral control adjectives, and each content category was split into
      negative and positive valence. The four-way interaction between group, reference,
      content and valence was significant both in the recall data and the endorsement
      data. Further analysis revealed that depressed pain patients exhibited a bias
      towards self-referential negative pain words, but not towards self-referential
      negative depression information. These results are interpreted in line with
      content specificity theory of information processing and have implications for
      targeting cognitive interventions with pain patients.

PMID- 7647719
TI  - Stability in the structure of health locus of control among adolescents.
AB  - The Multidimensional Health Locus of Control (MHLC) scales have been widely used
      as a measure of health beliefs in adult populations. In a longitudinal study of
      an adolescent cohort, we examined some of the properties of the MHLC; whether
      there are changes in the locus of beliefs between the ages of 13 and 15 years;
      and the extent of gender differences at the two ages. The results provided some
      degree of support for the previously proposed structure of the MHLC, but showed
      correlations among the subscales that were higher than might be expected, and
      lower alpha reliability coefficients than have been reported for adult samples.
      There was also evidence of downward changes in scores for the 'chance' and
      'powerful others' scales, as well as differences in the factor structures of
      females and males at age 15 years. In contrast to the structure of health beliefs
      found with some adult samples, 'chance' is a prominent, independent dimension of
      beliefs about control of health among adolescents. The independence of the
      'internal control' and 'powerful others' scales seem to be a function of both age
      and gender. As health behaviours are multidetermined, it is concluded that the
      MHLC measure would be useful as part of an index of health status.

PMID- 7647720
TI  - Subjective well-being of elderly women: conceptual differences between cancer
      patients, women suffering from chronic ailments and healthy women.
AB  - Studies have shown that the mean scores on global subjective well-being measures
      of cancer patients do not differ from the mean scores of other patient samples or
      samples of healthy individuals. These results give rise to speculations about the
      nature of the concept subjective well-being. Therefore, we compared the structure
      of the concept subjective well-being between three groups of elderly women
      (cancer patients, women suffering from chronic ailments and healthy women). This
      was done by examining the relationships between five dimensions of subjective
      well-being (perceived physical health, self-esteem, negative affect, optimism and
      loneliness) and two  measures of global subjective well-being (affective well
      being and life satisfaction) in each group of women. The results clearly
      demonstrate the differences in the relative importance of the five dimensions for
      the global evaluation of well-being between the three groups. The most notable
      finding was that perceived physical health appears to be more strongly related to
      global subjective well-being, when the objective health status is worse. The
      unequal relative importance of dimensions of subjective well-being should be
      taken into account when comparing the mean scores on subjective well-being
      measures between populations with different states of health.

PMID- 7647721
TI  - The effectiveness of a motion sickness counselling programme.
AB  - Unselected volunteers were offered a course of instruction in using the cognitive
      behavioural approach to helping individuals tolerate the deleterious effects of
      different motion environments. In order to evaluate that programme, 11 of the
      participants volunteered to counsel independently individuals who were prone to
      motion sickness, using cognitive-behavioural training which included
      reinforcement by visually induced apparent motion. The subjects were pre- and
      post-tested by an independent observer using tolerance and motion response as the
      dependent variables. These test scores were compared to previous data obtained
      with subjects who had received counselling from an experienced counsellor, or had
      received no such counselling. The results indicated that the newly trained
      counsellors' subjects showed significant pre- to post-test tolerance to the
      motion stimulus, although they did not benefit as much as subjects trained by the
      experienced counsellor. However, in terms of post-test symptomatology and
      magnitude estimates of motion sickness, the trainees' subjects exhibited as much
      benefit as did those of the experienced counsellor. These data are taken as
      strong support for the feasibility of training counsellors to employ this method
      of alleviating motion sickness.

PMID- 7647722
TI  - Post-traumatic stress disorder and war veterans.

PMID- 7647723
TI  - Rehabilitation of acquired visuospatial disorders.

PMID- 7647724
TI  - [Unverified and controversial diagnostic methods in allergology].

PMID- 7647725
TI  - [Characteristics of hay fever during pollen season with regard to the influence
      of specific immunotherapy. I. Clinical course and biochemical changes in nasal
      lavage].
AB  - Nasal lavage is a useful tool for monitoring of inflammatory process in
      pollinosis. In 27 patients with pollen allergy the nasal lavage was performed
      before, during and after pollen season. The concentration of total protein,
      albumin and lysozyme were determined in obtained fluid. In one group Pollinex
      (Bencard) was applied before pollen season, and in the second one--placebo in
      similar injections. The concentrations of total protein in nasal lavage fluid was
      significantly lower after the pollen season in both analyzed groups. On the other
      hand, the concentrations of albumin and lysozyme were increased during pollen
      season relatively to values before and after the season. In patients treated with
      Pollinex observed values after the season were lower than in placebo group.

PMID- 7647726
TI  - [Course of hay fever during the pollen season with respect to the effect of
      specific immunotherapy. II. Cytologic changes and chemotactic activity in nasal
      lavage].
AB  - The cytological changes and chemotactic activity in nasal lavage fluid were
      observed in 27 patients with pollen allergy. In one group of patients Pollinex
      was administered, but in the second--only placebo. Total cell count in nasal
      secretions was increased after pollen season. The significant increase of
      eosinophils and metachromatic cells was observed during the season in comparison
      with the time before and after it. No seasonal dynamic was documented in
      chemotactic activity of neutrophils in the nasal lavage fluid. Applied
      immunotherapy gave a some protection on evaluated parameters and observed
      symptoms.

PMID- 7647727
TI  - [Asthma, allergic rhinitis and atopic dermatitis in schoolchildren].
AB  - Many reports describe an increase in the incidence of allergies in recent years.
      Thus the epidemiological studies are necessary for efficacious prophylaxis. The
      aim of our study was to estimate the prevalence of allergic diseases in
      schoolchildren. Allergic rhinitis and/or conjunctivitis was observed in 16.7%.
      Atopic dermatitis occurred in 12.9% cases. We showed the discrepancy between the
      number of children with symptoms suggestive for asthma (wheezing--11.1%,
      breathlessness--19.4%, nocturnal cough--4.9%, exercise-induced cough--9.8%) and
      number of cases diagnosed as asthma (3.2%). Family history of allergy increased
      the risk of allergic diseases in studied population.

PMID- 7647728
TI  - [Concentration of eosinophil cationic protein in blood serum during early and
      late asthmatic reaction].
AB  - Eosinophil cationic protein (ECP) was measured in blood serum of 15 atopic
      asthmatics during early (EAR) and late (LAR) asthmatic reaction triggered by
      specific allergen provocation. Nonspecific bronchial hyperreactivity was
      evaluated in histamine provocation test before and 48 hours after the allergen
      challenge. We observed dual asthmatic reaction (DAR) in 8 and an isolated EAR in
      7 patients. The ECP serum level and nonspecific bronchial hyperreactivity were
      significantly higher (p < 0.05) in the DAR group when compared to EAR responders.
      An inverse correlation between PC20 for histamine and ECP level was shown before
      and after the allergen challenge in all examined subjects (R = -0.5472, p <
      0.05).

PMID- 7647729
TI  - [Peripheral blood eosinophilia in patients with bronchial asthma before and after
      bronchial provocation].
AB  - The study was set up in order to check the usefulness of peripheral blood
      eosinophilia in asthma diagnosis and asthma therapy monitoring. Twenty mild
      asthmatics entered the study--ten atopic and ten nonatopic. Eosinophilia was
      estimated twice: on the day of admission and twenty four hours after bronchial
      provocation. Bronchial hyperreactivity was measured on both occasions. We showed,
      that there was no difference in eosinophilia between atopic and nonatopic
      subjects before provocation but the difference was significant 24 hrs after
      provocation. In both groups of asthmatics eosinophilia correlated with bronchial
      hyperreactivity before and after provocation. We concluded, that eosinophilia is
      an easy and valuable parameter in monitoring the degree of allergic inflammation
      in asthmatics.

PMID- 7647730
TI  - [Oral immunotherapy in patients with hypersensitivity to plant pollen].
AB  - In 10 patients from 7-15, with seasonal symptoms of allergic disease of airways,
      conjunctives and nose oral hyposensitization was carried out. The patients were
      hyposensitized with grass pollen extracts produced by Sevac Firm. The pollen
      allergen was administered before pollinating season, in increasing doses
      recommended by the firm, during five month. The clinical effect, serum IgE
      allergen specific IgE (asIgE)--levels were assessed. In all patients after
      hyposensibilization milder symptoms were observed. Serum IgE - level was
      diminished in 7 patients. There was no change in as IgE levels.

PMID- 7647731
TI  - [Evaluation of one month treatment with flunisolide in perennial allergic
      rhinitis].
AB  - The study was carried out on a group of 20 patients ages 10-44. Syntaris was
      administered twice daily in a total dose of 100 mcg. Rhinitis symptoms were
      assessed by subjective scoring (graded 0-3) and by objective measurement of nasal
      airflow using anterior rhinomanometry. Syntaris proved to be a safe and effective
      drug particularly in improving nasal patency.

PMID- 7647732
TI  - [Effect of nedocromil sodium on clinical course and histamine airway
      responsiveness in patients with pollen induced bronchial asthma].
AB  - Nedocromil sodium is a non-steroidal prophylactic agent for the management of
      asthma. We assessed the effect of inhaled of nedocromil sodium 8 mg/24 h in a
      double blind, placebo controlled study in 14 patients suffering from seasonal
      (grass-pollen) asthma. Symptom scores for dyspnoe, cough, rhinitis and airway
      responsiveness to histamine (PC20H) according to Cockcroft et al were estimated
      before the grass-pollen season and at the end of 14-day placebo treatment and 21
      day nedocromil sodium treatment. During placebo period the significant decrease
      in PC20H from 1.81 mg/ml to 0.54 mg/ml (p < 0.01) was observed. Nedocromil sodium
      did not have the effect on nonspecific bronchial responsiveness, PC20 - 0.74
      mg/ml (p = 0.25). Subjective global assessment scores were significantly better
      with nedocromil sodium (31.15 mean 2.23) than with placebo (10.5 mean 0.7) p <
      0.05.

PMID- 7647733
TI  - [Bronchial reactivity after regular inhalation of salbutamol].
AB  - 15 patients with mild bronchial asthma were selected for study. They inhaled
      salbutamol 2.5 mg three times daily for 8 days. Bronchodilator dose-response
      studies were performed by administering increasing doses of isuprel intravenously
      before and after treatment with salbutamol. Histamine provocation was done to
      estimate airway responsiveness. That was performed prior to and after salbutamol
      therapy. Regular inhaled salbutamol increased airway responsiveness to histamine-
      Pc20 was significantly reduced from 1.95 mg/ml--before treatment to 0.44 mg/ml-
      after salbutamol therapy. The bronchodilatory effect after isuprel was the same
      before and after treatment with salbutamol.

PMID- 7647734
TI  - [Correlation between peak expiratory flow and selected indices of bronchial
      potency in children between 4 and 18 years of age].
AB  - The study was conducted on 474 children diagnosed at the Lung Function Laboratory
      of the Children' Hospital in Lublin in the year 1992. 55% of the analyzed
      children were males. The children's initial diagnosis were: bronchial asthma,
      allergic rhinitis, chronic respiratory disorders, diabetes mellitus,
      abnormalities of the thorax. In 28 children no abnormalities were detected. PEF
      was measured with a Peak Flow Meter produced by Vitalograph. Children in the age
      group 4-6 years had PEF measured with a mini meter, reading values between 0 to
      300 L/min. A standard meter was used for older children detecting values between
      0 to 700 L/min. Spirometry, MEFV curves, resistance were analyzed with the
      abcPNEUMO 2000 spirometer (abcMED). Correlation was calculated between PEF and
      FEV1, MEF25, MEF50, MEF75, PEF, PIF, FEV1%FVC, Raw. Multiple regression analysis
      was performed to identify the best subpopulation of independent variants. In all
      children a correlation was found between PEF and the major parameters of airways
      potency. The weakest correlation was found in children younger than 6 years. PEF
      correlated best with FEV1 and MEF75.

PMID- 7647735
TI  - [Chief editor of "Polish Pneumonology and Allergy"].

PMID- 7647736
TI  - [Evaluation of selected factors induced by antioxidative activity in serum of
      cigarette smokers and in patients with early phase emphysema].
AB  - We investigated the concentration of ceruloplasmin (CP), transferrin (T) and
      metal ions (Cu, Zn) in serum of healthy smokers, emphysema patients and healty
      non-smoking subjects (control). We observed elevated Cu concentration in smokers
      and emphysema patients. Elevated CP concentration was observed only in those
      emphysema patients who smoked cigarettes, but not in healthy smokers. This
      observation excludes the possibility of compensative CP and Cu increase as the
      effect of chronic oxidant exposure. Changes in concentration of CP and Cu
      observed by us are probably due to chronic inflammation of respiratory tract not
      only of emphysema patients but also of chronic smokers without signs of the
      disease.

PMID- 7647737
TI  - [Use of inhalation anesthetics in treatment of severe status asthmaticus and for
      anesthesia in children suffering from bronchial asthma. Preliminary report].
AB  - This paper presents preliminary estimation of clinical usefulness of isoflurane
      for treatment of severe cases of status asthmaticus in children and application
      of it as monoanesthesia in children with bronchial asthma, operated upon sudden
      indications. Action and metabolism of halogen ether group inhalatory anaesthetics
      in human organism was discussed, with special attention being paid to isoflurane
      and ketamine. In the cases studied (which is also confirmed by numerous clinical
      tests) potentialization of bronchodilatative effect of isoflurane by intravenous
      application of ketamine in status asthmaticus was observed. Where the results
      achieved was linked up with increased concentration of catecholamines and direct
      atonic effect on smooth muscular coat of bronchus.

PMID- 7647739
TI  - [Widening of mediastinal shadow in a 10-year old girl with allergic alveolitis].
AB  - The case of a 10 year old girl widening of mediastinal shadow in X-ray
      examination is presented. Allergic pulmonary alveolitis as a primary disease was
      found. The broadening of the mediastinal shadow depended on lymphadenopathy in
      the course of associated mycoplasma infection and vasculature pattern.

PMID- 7647738
TI  - [Psychogenic pseudo-asthmatic syndrome].
AB  - The authors present a case of a 42-year-old patient treated for severe attacks of
      dyspnoea and wheezing of 12 years duration. She was hospitalized 8 times in
      medical or pneumonology wards and underwent treatment in a sanatorium 6 times.
      Since 5 years she has been periodically and recently permanently on oral
      glucocorticosteroids. Dyspnoea was accompanied by diffuse wheezing and prolongs
      expiration. It was also observed that her mode of respiration during an attack
      consisted in forced expiration at small air volumes in the lungs. Theatrical
      behaviour of the patient was striking. Bronchial challenge with acetylcholine and
      metacholine was negative. Bronchoscopy revealed profound intussusception of the
      membraneous part of the trachea and bronchi. Psychiatric diagnosis confirmed
      hysterical personality. The demonstrated case proves that the value of bronchial
      challenge is difficult to overestimate in diagnosing asthma. It concerns not only
      cases where symptoms are scanty but also patients with the so-called troublesome
      treatment-resistant asthma.

PMID- 7647741
TI  - [Histamine receptors and their role in allergic diseases].

PMID- 7647740
TI  - [The role of interleukin-4 in allergic reactions].

PMID- 7647742
TI  - [Clinical significance of blood platelet activation in pathogenesis of
      respiratory tract disorders].

PMID- 7647743
TI  - Effects of freezing on DPT and DPT-IPV vaccines, adsorbed.

PMID- 7647744
TI  - Ebola hemorrhagic fever. A brief description.

PMID- 7647745
TI  - National guidelines for vaccine storage and transportation. The Childhood
      Immunization Division, Bureau of Communicable Disease Epidemiology, Laboratory
      Centre for Disease Control, Canada.

PMID- 7647746
TI  - Protecting vaccines from freezing in extremely cold environments.

PMID- 7647747
TI  - National Advisory Committee on Immunization (NACI) statement on influenza
      vaccination for the 1995-96 season.

PMID- 7647748
TI  - Relative satisfaction.

PMID- 7647749
TI  - An active solution for health.

PMID- 7647751
TI  - Responding to Alzheimer's.

PMID- 7647752
TI  - 'It doesn't happen here...'.

PMID- 7647750
TI  - Stroke care and rehabilitation.

PMID- 7647753
TI  - Where have the nurses gone?

PMID- 7647754
TI  - New guidance for health care needs.

PMID- 7647755
TI  - Lest we forget.

PMID- 7647756
TI  - Retirement at 80 policy--it failed.

PMID- 7647757
TI  - 'Revolving door syndrome'.

PMID- 7647758
TI  - Endoscopic sinus surgery: a fundamental approach.
AB  - Endoscopic sinus surgery has grown in popularity since its introduction in 1985.
      This procedure can be used to correct mechanical or structural dysfunction of the
      sinus to restore proper drainage and adequate ventilation. The surgical technique
      may be performed by direct visualization through the endoscope or by an indirect
      method using the video monitor. Patient outcomes have been improved through this
      less invasive procedure by decreased hospitalization time, decreased recovery
      time, and quicker return to normal activities of daily living.

PMID- 7647759
TI  - Laparoscopic-assisted vaginal hysterectomy: is it a genuine alternative?
AB  - Hysterectomy, the removal of the uterus, is one of the most common operative
      procedures performed in the United States. Traditionally, the procedure was
      either abdominal, with a laparotomy incision, or vaginal, with all dissection
      being performed through the vagina. Today a new alternative, the laparoscopic
      assisted vaginal hysterectomy, is available. It is an alternative to the
      abdominal hysterectomy, and is meant to reduce the percentage of abdominal versus
      vaginal hysterectomies. Laparoscopic-assisted vaginal hysterectomies may be
      performed on vaginal hysterectomy cases for learning purposes.

PMID- 7647760
TI  - Laparoscopic Nissen fundoplication.
AB  - Nissen fundoplication is the procedure of choice for gastroesophageal reflux. In
      the operating room at St Luke's Episcopal Hospital, Nissen fundoplication has
      been taken to another level. Because of the increasing trend in laparoscopic
      surgery and the advanced instruments available, laparoscopic Nissen
      fundoplication procedures are now performed on a routine basis. One advantage of
      laparoscopic Nissen fundoplication, as opposed to open Nissen fundoplication, is
      that the laparoscopic approach is far less invasive. It consists of five 11.5-mm
      incisions, whereas the open procedure involves a large midline incision. In
      addition, the overall hospital bill for the laparoscopic procedure can be less
      than that for an open one; for a laparoscopic Nissen fundoplication, the
      operating room bill is higher, but the hospital stay is shorter. Usually, the
      patient can go home the following day and resume daily tasks within days. With an
      open Nissen fundoplication, the hospital stay is about 3 to 5 days, and because
      of the large midline incision, a recovery time of 4 to 6 weeks is required. Not
      only can the patient resume daily activities sooner, but there is generally less
      pain associated with laparoscopic Nissen fundoplication, and the overall hospital
      bill is less because of the days spent in the hospital for postoperative
      recovery.

PMID- 7647761
TI  - Thoracoscopy: a collaborative surgical approach.
AB  - Perioperative nurses, surgeons, anesthesiologists, certified registered nurse
      anesthetists, and pharmacists are meeting the challenge of decreasing thoracic
      surgical patients' length of hospital stay with thoracoscopy. This innovative
      alternative to traditional thoracotomy procedures has been achieved through an
      attentive team approach using the fundamental perioperative skills of assessment,
      positioning, safety, and sharing of knowledge.

PMID- 7647762
TI  - Transmyocardial laser revascularization.
AB  - Transmyocardial laser revascularization is a technique to create new vessels in
      underperfused areas of the ischemic heart. These vessels carry blood directly
      from the left ventricle of the heart into the myocardium. Clinical trials of this
      technique are currently underway.

PMID- 7647763
TI  - Stereotactic radiosurgery: new practice frontiers for the perioperative nurse.
AB  - Stereotactic radiosurgery (SR) is a technology that blends the skill and
      technology of several disciplines such as neurosurgery, radiation oncology,
      radiology, engineering, medical physics, and nursing. The improvement of
      neurological imaging that occurred in the 1970s and 1980s provided diagnosticians
      with the technical foundation necessary to support parallel advancement of SR.
      Today, SR is used to treat pituitary tumors, meningiomas, acoustic neuromas,
      arteriovenous malformations, metastatic tumors of the brain, craniopharyngiomas,
      and residual gliomas. Participation in SR procedures provides the perioperative
      nurse with an opportunity to move beyond the walls of the operating suite into
      the exciting world of neurological imaging and radiotherapy.

PMID- 7647764
TI  - Advances in spinal surgery: pedicle screw implant fixation.
AB  - Spinal disorders resulting in back pain have become the subject of clinical and
      research activity. Developments in pedicle screw fixation has resulted in
      treatment of back pain for persons who previously maintained with ongoing pain
      and instability. This article summarizes some indications and systems used for
      correction of spinal disorders.

PMID- 7647765
TI  - Perioperative education: a center of excellence.
AB  - The responsibilities and areas of accountability of the perioperative nurse are
      growing. The Perioperative Education department at St Luke's Episcopal Hospital
      in Houston, TX has developed creative methods of orientation, critical pathways,
      and continuing education to meet the expectations of staff competency for all
      patient care.

PMID- 7647766
TI  - Mortyn Jones Memorial Lecture. Intracerebrally released vasopressin and oxytocin:
      measurement, mechanisms and behavioural consequences.

PMID- 7647767
TI  - Effects of monoclonal antibodies to specific epitopes of rat interleukin-1 beta
      (IL-1 beta) on IL-1 beta-induced ACTH, corticosterone and IL-6 responses in rats.
AB  - Recently, we developed a panel of monoclonal antibodies (MoAbs) to rat IL-1 beta
      and found that MoAbs binding to the aminoacid sequences 66-85 and 123-143 of
      mature rIL-1 beta inhibited the binding of rIL-1 beta to murine EL4 cells. Here
      we study whether MoAbs to these and other domains of IL-1 interfere with the
      biological effects of rIL-1 beta in adult male rats in vivo. Administration of
      rIL-1 beta (1 or 5 micrograms/kg i.v.) enhanced the plasma concentrations of
      ACTH, corticosterone (CORT) and of IL-6 in a time- (0.5-4 h) and dose-dependent
      manner. Because 2 h after 5 micrograms/kg i.v., all three parameters were
      consistently elevated, this dose and time interval was used for further studies.
      Prior to injection, rIL-1 beta was incubated alone or in the presence of a MoAb
      (10 mg/kg) for 30 min at 37 degrees C or at 4 degrees C. Plasma ACTH, CORT and IL
      6 responses to these mixtures are compared to those obtained after preincubation
      of rIL-1 beta with a non-IL-1 binding MoAb (PEN7). SILK 3, a MoAb that binds to
      the 66-85 domain of rIL-1 beta, reduced the ACTH and IL-6 responses by 48 and 45%
      respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7647769
TI  - Neuropeptide Y (NPY) may integrate responses of hypothalamic feeding systems and
      the hypothalamo-pituitary-adrenal axis.
AB  - Neuropeptide Y (NPY) is a powerful stimulus to food intake in the rat. Exogenous
      NPY given into the third ventricle or into the paraventricular nucleus (PVN) of
      the hypothalamus stimulates both food consumption as well as the hypothalamus
      pituitary-adrenal (HPA) axis. Presumably NPY activates the adrenocortical system
      through direct stimulation of CRF containing cells in the PVN. Food intake is
      also a major regulator of adrenocortical activation. Rhythms in HPA axis activity
      follow rhythms in food consumption, and rats that have been food deprived
      overnight have inhibited HPA axis responses to restraint stress and
      corticosteroid feedback the following morning. To investigate the interaction of
      NPY with both feeding and HPA axis activation three sets of experiments were
      performed: Animals fed ad lib were injected icv with NPY (2.5 micrograms) and
      allowed access to food or not post injection; animals were fasted overnight prior
      to NPY injection; finally, dose response experiments were performed to examine
      the relative sensitivities of feeding and HPA axis activation to exogenous NPY.
      Ad lib fed animals allowed access to food after NPY injection had slightly
      greater ACTH responses to NPY while glucocorticoid and insulin responses were not
      significantly different from ad lib fed animals not allowed access to food post
      injection. Animals allowed to eat post injection had significantly decreased food
      consumption the night following injection, however, total 24 h food consumption
      was not different between these animals and those given food 8 h post NPY
      injection. In overnight fasted animals NPY injections produced ACTH responses of
      equal magnitude to those in ad lib fed animals.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7647768
TI  - Expression of biologically active procorticotrophin-releasing hormone (proCRH) in
      stably transfected CHO-K1 cells: characterization of nuclear proCRH.
AB  - Corticotrophin-releasing hormone (CRH) is a 41 amino acid neuropeptide which is
      cleaved at a pair of dibasic amino acids from a larger precursor molecule (pre
      proCRH) by the action of endopeptidases. In cells possessing a regulated
      secretory pathway, sorting of proneuropeptides and prohormones occurs within the
      trans-Golgi network, where they are finally packaged into secretory vesicles to
      be released in response to an external stimulus. Such cells also possess a
      constitutive secretory pathway, and neuropeptides are also translocated into this
      subcellular compartment. We have recently established stably transfected CHO-K1
      cells expressing the rat pre-proCRH cDNA, and shown that proCRH was localized
      within the secretory pathway and the nucleus of transfected cells. Both the
      cytoplasmic and nuclear species of IR-CRH displayed an apparent molecular weight
      approximately 19 kDa, consistent with the size of the uncleaved CRH precursor
      molecule. In this paper, we further characterized the bitopological, i.e. nuclear
      and cytoplasmic localization of proCRH within transfected CHO-K1 cells.
      Immunoreactive nuclear CRH was not extractable using detergents (Triton X-100 and
      CHAPS), 10 mM salt washes or RNase digestion but could be abolished by digestion
      with DNase I. These results therefore suggest that nuclear proCRH is in close
      association with DNA/chromatin. Treatment of transfected cells with inhibitors of
      protein and RNA synthesis for up to 24 h had no effect upon immunoreactive
      nuclear CRH, indicating that it is very stable with a long half life. Brefeldin A
      treatment had no effect upon the nuclear translocation of newly synthesized
      proCRH, suggesting that late stages of the secretory pathway (i.e. post rough
      endoplasmic reticulum compartments) of the transfected cells do not play a role
      in proCRH nuclear transport. We also demonstrate that proCRH synthesized within
      stably transfected CHO-K1 cells is capable of stimulating ACTH release from
      primary cultures of anterior pituitary cells, therefore showing for the first
      time that the intact precursor is also biologically active and could act as an
      ACTH secretagogue in-vivo.

PMID- 7647770
TI  - Estrogen-sensitive oxytocin binding sites are differently regulated by
      progesterone in the telencephalon and the hypothalamus of the rat.
AB  - The localization at the cellular level and the regulation by progesterone of the
      estrogen-sensitive oxytocin binding sites was studied in the rat telencephalon
      and the hypothalamus by using quantitative film-autoradiography and
      histoautoradiography. Male rats (castrated or not) and ovariectomized females
      (estradiol supplemented or not) were used to characterize these sites and to
      precise their localization. They were detected in the striatal cell bridges, the
      olfactory tubercle, the principal nucleus of the bed nucleus of the stria
      terminalis and the medial nucleus of the amygdala of the telencephalon and in the
      medial preoptic, the ventromedial and the ventral premammillary nuclei of the
      hypothalamus. Estrogen administration in addition induced expression of oxytocin
      binding sites in the major island of Calleja, the anterior hypothalamic area and
      the terete nucleus. The density of the estrogen-sensitive oxytocin binding sites
      varied during the estrous cycle, but differently in the telencephalon and the
      hypothalamus. In the telencephalon it peaked at proestrus 9 h and was already
      decreased at proestrus 21 h, whereas in the hypothalamus it was similarly high at
      proestrus 9 h and proestrus 21 h, suggesting the intervention of progesterone in
      the regulation of the hypothalamic estrogen-sensitive oxytocin binding sites.

PMID- 7647771
TI  - Evidence that hypothalamic neuropeptide Y gene expression increases before the
      onset of the preovulatory LH surge.
AB  - Neuropeptide Y (NPY), a 36 amino acid residue peptide, is involved in stimulation
      of LHRH and LH surges on proestrus and those induced by ovarian steroids in
      ovariectomized (ovx) rats. Recently, we observed that NPY gene expression in the
      medial basal hypothalamus (MBH) was increased before the onset of the LH surge in
      the ovarian steroid-primed ovx rats. Since the ovarian steroidal milieu during
      the estrous cycle is markedly different from that prevailing after ovarian
      steroid injections in ovx rats, we evaluated in cycling rats the temporal
      relationship between MBH preproNPY mRNA levels and the preovulatory LH surge on
      the day of proestrus and compared that with diestrus II, concomitant with basal
      LH levels. PreproNPY mRNA levels in the MBH were measured by solution
      hybridization/RNAse protection assay, using a cRNA probe. On the day of diestrus
      II, preproNPY mRNA levels changed little between 1000 and 1800 h. Quite
      unexpectedly, preproNPY mRNA levels at 1000 h on proestrus were similar to
      diestrus II levels, despite additional exposure to ovarian steroids during this
      interval. However, from these low levels at 1000 h, the preproNPY mRNA profile
      displayed a biphasic rise. During the first phase, preproNPY mRNA rose
      significantly at 1200 h and remained elevated at 1300 and 1400 h concomitant with
      basal serum LH levels. Thereafter, a second rise in preproNPY mRNA began at 1500
      h, peaked rapidly at 1600 h and declined significantly at 1800 h.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7647772
TI  - Neuropeptide-E-I antagonizes the action of melanin-concentrating hormone on
      stress-induced release of adrenocorticotropin in the rat.
AB  - The physiological role of melanin-concentrating hormone (MCH) in mammals is still
      very elusive, but this peptide might participate in the central control of the
      hypothalamopituitary adrenal (HPA) axis during adaptation to stress. Cloning and
      sequencing of the rat MCH (rMCH) cDNA revealed the existence of additional
      peptides encoded into the MCH precursor. Among these peptides, neuropeptide (N)
      glutamic acid (E) isoleucine (I) amide (NEI) is co-processed and secreted with
      MCH in rat hypothalamus. In the present work we examined: (1) The pattern of rMCH
      mRNA expression during the light and dark conditions in the rat hypothalamus and
      (2) The effect of intracerebroventricular (ICV) injections of rMCH and NEI in the
      control of basal or ether stress-modified release of corticotropin (ACTH),
      prolactin (PRL) and growth hormone (GH) secretion in vivo in light-on and light
      off conditions. Our data indicate that rMCH mRNA levels do not change during the
      light-on period, but increase after the onset of darkness. Either alone or co
      administered, rMCH and NEI do not modify basal secretion of GH and PRL at any
      time tested nor do they alter ether stress-induced changes in these two hormonal
      secretions. At the end of the light on period corresponding to the peak of the
      circadian rhythm in ACTH, administration of rMCH but not NEI leads to a decrease
      in ACTH levels while MCH is not effective during the light off period of the
      cycle (i.e. when basal ACTH levels are already low). Using a moderate ether
      induced stress, ACTH levels are only stimulated during the dark phase of the
      cycle.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7647773
TI  - The C-type natriuretic peptide receptor is the predominant natriuretic peptide
      receptor mRNA expressed in rat hypothalamus.
AB  - The natriuretic peptide receptors (NPR) are membrane-bound guanylate cyclases
      with extracellular binding domains specific for particular members of the
      natriuretic peptide family. NPR-A binds atrial natriuretic peptide (ANP) with
      high affinity, whereas the NPR-B appears to be specific for C-type natriuretic
      peptide (CNP). Previous data indicating extensive overlap between localization of
      ANP and CNP in hypothalamic neuroendocrine circuits suggest the importance of
      determining whether specificity of natriuretic peptide action may be conferred
      via receptor type present on target cells. To address this issue, we used in situ
      hybridization histochemistry to localize NPR-A and NPR-B mRNA in the
      hypothalamus. NPR-A mRNA was not found in substantial abundance in any
      hypothalamic nucleus; however, detectable NPR-A signal was observed in other
      brain regions, including the subfornical organ and medial habenula. In contrast,
      NPR-B mRNA was expressed throughout the hypothalamus, including neurons of the
      magnocellular and parvocellular paraventricular, the arcuate, and the supraoptic
      nuclei. Expression was also seen in other nuclei essential to neuroendocrine
      control, including the median preoptic, anteroventral periventricular,
      tuberomammilary, ventromedial and suprachiasmatic nuclei. NPR-B mRNA was also
      observed in the neural lobe of the pituitary gland, suggesting expression by
      pituicytes. The results suggest that NPR-B is the primary natriuretic peptide
      receptor in hypothalamus, and by inference indicate that CNP is the primary
      active natriuretic peptide in neuroendocrine regulation.

PMID- 7647774
TI  - Hypothalamic mediation of reduced GH secretion in diabetic rats: evidence for
      reduced cholinergic inhibition of somatostatin release.
AB  - The Goto-Kakizaki (GK) rat is a new model of diabetes mellitus and in this study
      we have characterized the diabetic and growth hormone (GH) secretory status of
      male GK rats at 6 and 16 weeks of age. We have also investigated the role of
      endogenous somatostatin (SS) and cholinergic manipulation on the GH responses to
      GH-releasing hormone (GHRH). GK rats were non-obese with significant fasting
      hyperglycaemia, hyperinsulinaemia and absent insulin responses to IV glucose. The
      GH response to GHRH was reduced at 16 weeks compared with normal, age-matched
      Wistar rats but no differences were observed at 6 weeks. Pretreatment of older
      rats (16 weeks) with anti-somatostatin antibodies (SS-Ab) significantly increased
      GH responses to GHRH in both normal and GK groups. Cholinergic augmentation with
      pyridostigmine (PD) reversed the blunted GH responses to GHRH in older GK rats
      but had no effect in the normal or young (6 weeks) GK rats. These results
      indicate that SS release mediates the blunted GH response to GHRH in GK rats and
      that reduced hypothalamic cholinergic signalling to the somatostatinergic neurone
      may mediate the increase in SS release. This view is supported by the results
      from in vitro studies in which cholinergic muscarinic blockade with pirenzepine
      (PIR) caused dose-related stimulation of SS release from normal rat hypothalami
      but was without effect on GK rat hypothalami. The cause of this alteration in
      hypothalamic function is, at present, unknown.

PMID- 7647775
TI  - Influence of environmental colour and diurnal phase on MCH gene expression in the
      trout.
AB  - Melanin-concentrating hormone (MCH) gene expression in the brain of rainbow
      trout, reared and maintained in either pale or black-coloured tanks, was studied
      using in situ hybridization histochemistry. MCH transcripts were most prevalent
      in the magnocellular neurones of the nucleus lateralis tuberis (NLT), which
      project to the pituitary gland. They were also present, although at much lower
      levels, in dorsally projecting parvocellular neurones, sited more posteriorly
      above the lateral ventricular recess (LVR). In the NLT the most intense
      hybridization signal was seen over the pituitary stalk; above the LVR, the most
      active neurones were located caudally. In both the NLT and above the LVR, MCH
      hybridization signal was 4-fold stronger in white-reared fish than in black
      reared fish. There was also a marked diurnal variation in MCH expression in both
      sites, with high levels at 16.00 h and lower levels at 04.00 h. The results show
      that gene activity in both hormonal (NLT) and neuromodulator/neurotransmitter
      (LVR) MCH neurones is induced by pale environmental colour and that MCH gene
      activity is subject to pronounced diurnal variation.

PMID- 7647776
TI  - Challenging genomic integrity.

PMID- 7647777
TI  - Cellular localization of the Huntington's disease protein and discrimination of
      the normal and mutated form.
AB  - Huntington's disease (HD) results from the expansion of a polyglutamine encoding
      CAG repeat in a gene of unknown function. The wide expression of this transcript
      does not correlate with the pattern of neuropathology in HD. To study the HD gene
      product (huntingtin), we have developed monoclonal antibodies raised against four
      different regions of the protein. On western blots, these monoclonals detect the
      approximately 350 kD huntingtin protein in various human cell lines and in neural
      and non-neural rodent tissues. In cell lines from HD patients, a doublet protein
      is detected corresponding to the mutated and normal huntingtin.
      Immunohistochemical studies in the human brain using two of these antibodies
      detects the huntingtin in perikarya of some neurons, neuropiles, varicosities and
      as punctate staining likely to be nerve endings.

PMID- 7647778
TI  - Stop codon FGFR3 mutations in thanatophoric dwarfism type 1.

PMID- 7647779
TI  - A candidate genetic risk factor for vascular disease: a common mutation in
      methylenetetrahydrofolate reductase.
AB  - Hyperhomocysteinaemia has been identified as a risk factor for cerebrovascular,
      peripheral vascular and coronary heart disease. Elevated levels of plasma
      homocysteine can result from genetic or nutrient-related disturbances in the
      trans-sulphuration or re-methylation pathways for homocysteine metabolism. 5, 10
      Methylenetetrahydrofolate reductase (MTHFR) catalyzes the reduction of 5, 10
      methylenetetrahydrofolate to 5-methyltetrahydrofolate, the predominant
      circulatory form of folate and carbon donor for the re-methylation of
      homocysteine to methionine. Reduced MTHFR activity with a thermolabile enzyme has
      been reported in patients with coronary and peripheral artery disease. We have
      identified a common mutation in MTHFR which alters a highly-conserved amino acid;
      the substitution occurs at a frequency of approximately 38% of unselected
      chromosomes. The mutation in the heterozygous or homozygous state correlates with
      reduced enzyme activity and increased thermolability in lymphocyte extracts; in
      vitro expression of a mutagenized cDNA containing the mutation confirms its
      effect on thermolability of MTHFR. Finally, individuals homozygous for the
      mutation have significantly elevated plasma homocysteine levels. This mutation in
      MTHFR may represent an important genetic risk factor in vascular disease.

PMID- 7647780
TI  - Mutations associated with familial melanoma impair p16INK4 function.
AB  - Cell division is controlled by a series of positive and negative regulators which
      act at sequential points throughout the cell cycle. Disturbance of these checks
      could contribute to cancer by allowing excessive cell proliferation. The point in
      G1 at which cells irrevocably commit to DNA synthesis is controlled by protein
      complexes consisting of cyclin-dependent kinases (CDK4 or CDK6) and cyclins (D1,
      D2 or D3). These complexes are inhibited by low molecular weight proteins, such
      as p16INK4 (refs 1,2), p15INK4B (ref. 3) and p18 (ref. 4). Deletion or mutation
      of these CDK-inhibitors could lead to unchecked cell growth, suggesting that
      members of the p16INK4 family may be tumour suppressor genes. The recent
      detection of p16INK4 (MTS1) mutations in familial melanoma kindreds, many human
      tumour cell lines, and primary tumours is consistent with this idea. Previously,
      we described eight germline p16INK4 substitutions in 18 familial melanoma
      kindreds. Genetic analyses suggested that five mutations predisposed carriers to
      melanoma, whereas two missense mutations had no phenotypic effect. We now
      describe biochemical analyses of the missense germline mutations and a single
      somatic mutation detected in these families. Only the melanoma-predisposing
      mutants were impaired in their ability to inhibit the catalytic activity of the
      cyclin D1/CDK4 and cyclin D1/CDK6 complexes in vitro. Our data provide a
      biochemical rationale for the hypothesis that carriers of certain p16INK4
      mutations are at increased risk of developing melanoma.

PMID- 7647781
TI  - Localization of a gene for autosomal dominant nocturnal frontal lobe epilepsy to
      chromosome 20q 13.2.
AB  - The epilepsies comprise a group of syndromes that are divided into generalized
      and partial (focal) types. Familial occurrence has long been recognized but
      progress in mapping epilepsy genes has been slow except for rare cases where the
      inheritance is easily determined from classical genetic studies. Linkage is
      established for three generalized syndromes: the EBN1 and EBN2 genes for benign
      familial neonatal convulsions (BFNC) map to chromosomes 20q and 8q (refs 2-5),
      the EPM1 gene for Unverricht-Lundborg disease maps to 21q (ref. 6) and the gene
      for the northern epilepsy syndrome maps to 8p (ref. 7). A claim for linkage of
      the EJM1 gene for the common generalized syndrome of juvenile myoclonic epilepsy
      to 6p is currently in dispute. Autosomal dominant nocturnal frontal lobe epilepsy
      (ADNFLE) was recently described in five families. We now report the chromosomal
      assignment, to 20q13.2, for the gene for ADNFLE in one large Australian kindred
      with 27 affected individuals spanning six generations.

PMID- 7647782
TI  - Targeted disruption of the mouse factor VIII gene produces a model of haemophilia
      A.
AB  - Haemophilia A is a classic X-linked disease which affects 1 in 5-10,000 males in
      all populations and is caused by defects in coagulation factor VIII. Roughly 60%
      of patients have severe disease with factor VIII activity < 1% of normal; they
      have frequent spontaneous bleeding into joints, soft tissues, muscles and
      internal organs. These patients usually require regular injections of plasma
      derived or recombinant human factor VIII. Because this is expensive and can
      potentially lead to life-threatening complications, other forms of therapy,
      including gene therapy, have been proposed. Natural canine models of factor VIII
      and factor IX deficiency have been available for many years, and gene therapy
      attempts on these dogs have met with partial success. However, a small animal
      model of the disease is desirable for studies of factor VIII function and gene
      therapy. Using gene targeting, we have made a mouse with severe factor VIII
      deficiency.

PMID- 7647783
TI  - Cloning of the gene for ocular albinism type 1 from the distal short arm of the X
      chromosome.
AB  - Ocular albinism type 1 (OA1) is an X-linked disorder characterized by severe
      impairment of visual acuity, retinal hypopigmentation and the presence of
      macromelanosomes. We isolated a novel transcript from the OA1 critical region in
      Xp22.3-22.2 which is expressed at high levels in RNA samples from retina,
      including the retinal pigment epithelium, and from melanoma. This gene encodes a
      protein of 424 amino acids displaying several putative transmembrane domains and
      sharing no similarities with previously identified molecules. Five intragenic
      deletions and a 2 bp insertion resulting in a premature stop codon were
      identified from DNA analysis of patients with OA1, indicating that we have
      identified the OA1 gene.

PMID- 7647784
TI  - CpNpG methylation in mammalian cells.
AB  - In vertebrate DNA, 3% to 5% of cytosine residues are present as 5-methylcytosine,
      and it is generally accepted that essentially all of this methylation occurs at
      cytosines which are contained in the symmetrical dinucleotide CpG. In this report
      we demonstrate, using bisulphite genomic sequencing, that the methylation
      machinery of mammalian cells is capable of both maintenance and de novo
      methylation at CpNpG sites. The existence of inherited CpNpG methylation in
      mammalian cells has important implications in gene regulation and in the
      aetiology of disease.

PMID- 7647785
TI  - A lipoprotein lipase mutation (Asn291Ser) is associated with reduced HDL
      cholesterol levels in premature atherosclerosis.
AB  - A reduction of high density lipoprotein cholesterol (HDC) is recognized as an
      important risk factor for coronary artery disease (CAD). We now show in
      approximately 1 in 20 males with proven atherosclerosis that an Asn291Ser
      mutation in the human lipoprotein lipase (LPL) gene is associated with
      significantly reduced HDL levels (P = 0.001) and results in a significant
      decrease in LPL catalytic activity (P < 0.0009). The relative frequency of this
      mutation increases in those patients with lower HDL cholesterol levels. In vitro
      mutagenesis and expression studies confirm that this change is associated with a
      significant reduction in LPL activity. Our data support the relationship between
      LPL activity and HDL-C levels, and suggest that a specific LPL mutation may be a
      factor in the development of atherosclerosis.

PMID- 7647786
TI  - Gain of glutamines, gain of function?

PMID- 7647787
TI  - Loss of function effect of RET mutations causing Hirschsprung disease.
AB  - We have introduced three Hirschsprung (HSCR) mutations localized in the tyrosine
      kinase domain of RET into the RET/PTC2 chimaeric oncogene which is capable of
      transforming NIH3T3 mouse fibroblasts and of differentiating pC12 rat
      pheochromocytoma cells. The three HSCR mutations abolished the biological
      activity of RET/PTC2 in both cell types and significantly decreased its tyrosine
      phosphorylation. By contrast, a rare polymorphism in exon 18 does not alter the
      transforming capability of RET/PTC2 or its tyrosine phosphorylation. These data
      suggest a loss of function effect of HSCR mutations which might act through a
      dominant negative mechanism. Our model system is therefore capable of
      discriminating between causative HSCR mutations and rare polymorphisms in the
      tyrosine kinase domain of RET.

PMID- 7647788
TI  - Partial epilepsy: chinks in the armour.

PMID- 7647789
TI  - Evidence for a susceptibility locus for schizophrenia on chromosome 6pter-p22.
AB  - We have performed linkage analysis in 186 multiplex families to search for genes
      that predispose to schizophrenia. Under a model with partially dominant
      inheritance, moderately broad disease definition and assuming locus homogeneity,
      a lod score of 3.2 was obtained for D6S260 on chromosome 6p23. A multipoint lod
      score of 3.9 (P = 2.3 x 10(-5)) was achieved when the F13A1 and D6S260 loci were
      analysed, allowing for locus heterogeneity. Adjusted for testing of multiple
      models, the multipoint lod score of 3.9 under heterogeneity has a genome wide
      significance of between 5-8%. The nonparametric affected pedigree member test
      provided results (P = 3 x 10(-4)) also supporting this finding. Our findings
      provide supportive evidence for a susceptibility locus for schizophrenia on
      distal chromosome 6p, and support a model of locus heterogeneity.

PMID- 7647790
TI  - MtDNA mutation in MERRF syndrome causes defective aminoacylation of tRNA(Lys) and
      premature translation termination.
AB  - We have investigated the pathogenetic mechanism of the mitochondrial tRNA(Lys)
      gene mutation (position 8344) associated with MERRF encephalomyopathy in several
      mitochondrial DNA (mtDNA)-less cell transformants carrying the mutation and in
      control cells. A decrease of 50-60% in the specific tRNA(Lys) aminoacylation
      capacity per cell was found in mutant cells. Furthermore, several lines of
      evidence reveal that the severe protein synthesis impairment in MERRF mutation
      carrying cells is due to premature termination of translation at each or near
      each lysine codon, with the deficiency of aminoacylated tRNA(Lys) being the most
      likely cause of this phenomenon.

PMID- 7647791
TI  - Localization of a gene for partial epilepsy to chromosome 10q.
AB  - There is strong evidence for a genetic contribution to epilepsy, but it is
      commonly assumed that this genetic contribution is limited to 'generalized'
      epilepsies, and that most forms of 'partial' epilepsy are nongenetic. In a
      linkage analysis of a single family containing 11 affected individuals, we
      obtained strong evidence for localization of a gene for partial epilepsy. This
      susceptibility gene maps to chromosome 10q, with a maximum two-point lod score
      for D10S192 of 3.99 at theta = 0.0. All affected individuals share a single
      haplotype for seven tightly linked contiguous markers; the maximum lod score for
      this haplotype is 4.83 at theta = 0.0. Key recombinants place the susceptibility
      locus within a 10 centimorgan interval.

PMID- 7647792
TI  - The low down on lipoprotein lipase.

PMID- 7647793
TI  - Amyotrophic lateral sclerosis associated with homozygosity for an Asp90Ala
      mutation in CuZn-superoxide dismutase.
AB  - Recent reports have shown heterozygosity for some twenty different mutations in
      the CuZn-superoxide dismutase (CuZn-SOD) gene in familial amyotrophic lateral
      sclerosis (FALS), and analysed samples from patients have shown decreased enzymic
      activity. Here we report homozygosity for an exon 4 mutation, Asp90Ala in
      fourteen patients among four unrelated ALS families and four apparently sporadic
      ALS patients from Sweden and Finland. The erythrocyte CuZn-SOD activity is
      essentially normal. Our findings suggest that this CuZn-SOD mutation causes ALS
      by a gain of function rather than by loss, and that the Asp90Ala mutation is less
      detrimental than previously reported mutations.

PMID- 7647794
TI  - Comparative sequence analysis of the human and pufferfish Huntington's disease
      genes.
AB  - The Huntington's disease (HD) gene encodes a novel protein with as yet no known
      function. In order to identify the functionally important domains of this
      protein, we have cloned and sequenced the homologue of the HD gene in the
      pufferfish, Fugu rubripes. The Fugu HD gene spans only 23 kb of genomic DNA,
      compared to the 170 kb human gene, and yet all 67 exons are conserved. The first
      coding exon, the site of the disease-causing triplet repeat, is highly conserved.
      However, the glutamine repeat in Fugu consists of just four residues. We also
      show that gene order may be conserved over longer stretches of the two genomes.
      Our work describes a detailed example of sequence comparison between human and
      Fugu, and illustrates the power of the pufferfish genome as a model system in the
      analysis of human genes.

PMID- 7647795
TI  - The reeler gene encodes a protein with an EGF-like motif expressed by pioneer
      neurons.
AB  - We have identified a strong candidate cDNA for the mouse reeler gene. This 5 kb
      transcript encodes a 99.4 kD protein consisting of 881 amino acids and possessing
      two EGF-like motifs. We assayed two independent mutant alleles--'Jackson reeler',
      which has a deletion of the entire gene, and 'Orleans reeler' which exhibits a
      220 bp deletion in the open reading frame, including the second EGF-like motif
      and resulting in a frame shift. In situ hybridization reveals that the transcript
      is detected exclusively in the pioneer neurons which guide neuronal cell
      migration along the radial array. Our findings offer an explanation for how the
      reeler mutant phenotype causes a disturbance of the complex architecture of the
      neuronal network.

PMID- 7647796
TI  - Nemaline myopathy mechanism.

PMID- 7647797
TI  - Linkage findings in bipolar disorder.

PMID- 7647798
TI  - The gene for autosomal dominant cerebellar ataxia with pigmentary macular
      dystrophy maps to chromosome 3p12-p21.1.
AB  - Autosomal dominant cerebellar ataxia with pigmentary macular dystrophy (ADCA type
      II) is a rare neurodegenerative disorder with marked anticipation. We have mapped
      the ADCA type II locus to chromosome 3 by linkage analysis in a genome-wide
      search and found no evidence for genetic heterogeneity among four families of
      different geographic origins. Haplotype reconstruction initially restricted the
      locus to the 33 cM interval flanked by D3S1300 and D3S1276 located at 3p12-p21.1.
      Combined multipoint analysis, using the Zmax-1 method, further reduced the
      candidate interval to an 8 cM region around D3S1285. Our results show that ADCA
      type II is a genetically homogenous disorder, independent of the heterogeneous
      group of type I cerebellar ataxias.

PMID- 7647799
TI  - Retinal degeneration characterizes a spinocerebellar ataxia mapping to chromosome
      3p.
AB  - A heterogeneous group of neurological disorders known as the spinocerebellar
      ataxias (SCA) are characterized by degeneration of the cerebellum, spinal cord
      and brainstem. We describe linkage analysis in four unusual SCA families
      revealing a distinct disease locus on chromosome 3p14-21.1. The disease in these
      families is distinguished from other forms of SCA by concomitant retinal
      degeneration. Initial visual problems leading to blindness, disabling ataxia and
      anticipation are seen in all kindreds. The anticipation in these families
      suggests a dynamic mutation at this locus. Eventual molecular characterization of
      this disease may provide valuable insights into the processes of both neural and
      retinal degeneration.

PMID- 7647800
TI  - Single-minded and Down syndrome?

PMID- 7647801
TI  - Expression analysis of the ataxin-1 protein in tissues from normal and
      spinocerebellar ataxia type 1 individuals.
AB  - Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurodegenerative
      disorder caused by expansion of a CAG trinucleotide repeat which codes for
      glutamine in the protein ataxin-1. We have investigated the effect of this
      expansion on ataxin-1 by immunoblot analysis. The wild-type protein is detected
      in both normal and affected individuals; however, a mutant protein which varies
      in its migration properties according to the size of the CAG repeat is detected
      in cultured cells and tissues from SCA1 individuals. The protein has a nuclear
      localization in all normal and SCA1 brain regions examined but a cytoplasmic
      localization of ataxin-1 was also observed in cerebellar Purkinje cells. Our data
      show that in SCA1, the expanded alleles are faithfully translated into proteins
      of apparently normal stability and distribution.

PMID- 7647803
TI  - Imaging of pelvic floor contractions using MRI.
AB  - Magnetic resonance was used to visualize the effect of voluntary pelvic floor
      contractions on the abdominal structures with particular emphasis in determining
      the dynamic relationship between the bladder and surrounding organs. The pelvic
      floor was imaged in 6 asymptomatic female volunteers using MRI viewed in seven
      coronal and seven sagittal planes. The relative displacement of the bladder
      resulting from voluntary pelvic floor contraction was measured and the changes
      from the relaxed to the contracted stage were identified. Measurements from
      sagittal images show superior bladder wall movement of 3.8 +/- 1.3 mm, posterior
      of 7.0 +/- 2.8 mm, while maximum movement in the gluteal region was 3.5 +/- 4.0
      mm. The results show that voluntary contractions of the pelvic floor measured and
      visualized using this technique can be identified and displayed using image
      processing techniques. Anatomical displacement of the bladder in the superior
      direction is illustrated, demonstrating that pelvic floor contraction provides
      increased levator muscle support. There is no significant displacement of the
      anterior aspect of the bladder, while the posterior wall demonstrates maximum
      movement.

PMID- 7647804
TI  - Estimation of the lag time between detrusor pressure- and flow rate-signals.
AB  - In a urodynamic measurement setup there is a considerable spatial separation
      between the uroflowmeter and the location where the detrusor pressure is
      measured. Therefore, a "time shift" (or lag time correction) has to be applied to
      one of these signals in order to align related samples in studies where pressure
      and flow rate are considered simultaneously (e.g., assessment of bladder
      contractility or bladder outlet resistance). Currently, a heuristic value for
      this time shift of 0.8 s is applied. In this article, we present a method to
      estimate the lag time directly from the measurements. Using this method we have
      found, amongst others, that the mean lag time in our clinic is 0.6 s for males,
      0.4 s for females voiding in sitting position, and 1.1 s for females voiding in
      standing position using a special receptacle in video urodynamics. Furthermore,
      we found that sphincter/urethral activity during voiding (which causes a drop in
      flow rate and an accompanying increase in detrusor pressure) is associated (on
      average) with shorter lag times than straining (when a positive pressure rise
      accompanies an increase in flow rate). Additionally strong evidence is provided
      that lag time correction is not a major source of error in urodynamics.

PMID- 7647805
TI  - Urodynamic comparison of ileum vs. sigmoid in augmentation cystoplasty for
      neurogenic bladder dysfunction.
AB  - We performed multichannel urodynamics before and after augmentation cystoplasty
      in 26 patients (11 females, 15 males) to determine which bowel segment is best to
      achieve a large volume and low pressure reservoir. All 26 patients had a
      neurogenic cause for their bladder dysfunction. Ileum was used in 14 patients and
      sigmoid was used in 12 patients. Detubularization was performed in all patients.
      Capacity improved significantly in both the ileum and the sigmoid group after
      surgery. When detubularized ileum was used, the maximum amplitude of uninhibited
      reservoir contractions was significantly improved or eliminated postoperatively.
      When sigmoid was used, uninhibited reservoir contractions did not significantly
      improve postoperatively and were, in fact, more common than preoperatively.
      Despite the detubularization, pressure waves were identified in 15 of the 26
      patients postoperatively. There was significant improvement in end filling
      pressures at capacity (compliance) with both ileum and sigmoid postoperatively.
      However, end filling pressures were significantly higher in the sigmoid group. In
      conclusion, good capacity was achieved with both ileum and sigmoid
      postoperatively. However, ileum provided lower reservoir pressures and better
      compliance. We feel that urodynamically detubularized ileum is better suited than
      sigmoid for augmentation cystoplasty in patients with neurogenic bladder
      dysfunction.

PMID- 7647802
TI  - Abnormal gene product identified in hereditary dentatorubral-pallidoluysian
      atrophy (DRPLA) brain.
AB  - Dentatorubral-pallidoluysian atrophy (DRPLA) is associated with the expansion of
      an unstable CAG repeat. Using antibodies against a synthetic peptide
      corresponding to the sequence of the DRPLA gene product C terminus, we have
      identified the DRPLA gene product in normal human brains as a approximately 190
      kD protein. We also find a larger approximately 205 kD protein specifically in
      DRPLA brains. Immunohistochemically, the DRPLA gene product is observed mainly in
      the neuronal cytoplasm. Our results demonstrate the existence of the expanded CAG
      repeat gene product and support the possibility that the expanded CAG-encoded
      polyglutamine stretch may participate in the pathological process of the similar
      trinucleotide repeat diseases.

PMID- 7647806
TI  - Reduced variance of latencies in pudendal evoked potentials after normalization
      for body height.
AB  - The value of the Somatosensory Evoked Potentials (SEP) in the assessment and
      detection of neurological disorders could be considerably enhanced if the
      normative standards of (SEP) characteristic parameters were normalized taking
      into account all other systematic sources of variance. The present study examines
      the influence of body height on the peak and interpeak latencies of the pudendal
      somatosensory evoked potentials. We examined the peak latency (L1) of the evoked
      potential recorded at the L1 vertebra and the onset latency (ONc) of the cortical
      evoked potentials, after stimulation of the pudendal nerve, as a function of body
      height in 40 normal male subjects (age 20-40 years). Significant positive
      correlation was found between both (ONc) latency and ONc-L1 interpeak latency and
      body height (H). Assuming that the latter is proportional to the length of the
      neural pathways, the experimental data were fitted using a theoretical model
      representing the conduction in the sensory neuraxis as a function of body height.
      Using the estimated fitting functions, we normalized our data with regard to a
      typical value of body height. The normalized values of the aforementioned
      latencies reveal a significantly reduced variance, as compared to the original
      ones, and consequently their diagnostic importance is significantly increased.
      Similar procedures applied to the L1 (spinal) latencies and the latencies of the
      bulbocavernosus reflex (BCR) reveal no correlation with body height and this is
      discussed on the basis of neuroanatomical considerations.

PMID- 7647807
TI  - Neurogenic bladder in patients with acquired immunodeficiency syndrome.
AB  - We have performed a urodynamic study on 3 patients with acquired immunodeficiency
      syndrome (AIDS), presenting with a neurogenic bladder. The first patient had an
      ascending myelitis of probable herpetic origin, the second patient had a cerebral
      abscess caused by Toxoplasma gondii, and the third patient had an AIDS dementia
      complex. The urodynamic study showed an areflexic detrusor in the first 2
      patients, and a hyperreflexic detrusor in the third patient.

PMID- 7647809
TI  - Morphological, stereological, and biochemical analysis of the mini-pig urinary
      bladder after chronic outflow obstruction and after recovery from obstruction.
AB  - Chronic partial bladder outlet obstruction was created in nine mini-pigs by
      implanting a 6-7 mm ring around the proximal urethra. After a median obstruction
      period of 63 days, the ring was removed and after a recovery period of median 60
      days the animals were sacrificed. Changes in muscle and connective tissue were
      assessed by unbiased, modern morphometry and biochemical analysis. After
      obstruction the results were as follows: (1) a 6-fold increase in bladder weight,
      (2) a 2.5-fold increase in smooth muscle cell size, (3) a 3-fold increase in
      smooth muscle cell number, (4) unchanged proportions between muscle and
      connective tissue, (5) unchanged hydroxyproline concentrations, (6) an 8-fold
      increase in total collagen content, (7) an increase in the ratio of type I/III
      collagen, and (8) a 7-8-fold increase in total content of type I and III
      collagen. All changes were markedly, though incompletely, reversed after
      recovery, except smooth muscle cell number and the ratio of type I/III collagen.

PMID- 7647808
TI  - Use of injectable fat to obstruct the urethra in rabbits.
AB  - Bulking agents have been injected to correct urinary incontinence for at least 15
      years. The injection seeks to increase bladder outlet resistance by partially
      obstructing the urethra and thereby reduce urinary leakage in patients with
      stress urinary incontinence. Although the implant is effective and requires a
      shorter in-hospital stay than more traditional procedures, no ideal implant
      substance has been discovered. To assess the effectiveness of injected fat as a
      bulking agent, we injected small volumes of perivesical fat into the bladder neck
      in New Zealand White (NZW) rabbits and tested the effect on the bladder. In eight
      rabbits, we harvested perivesical fat and partially closed the urethral lumen
      with an initial injection. A second injection 1 month later completely closed the
      urethral lumen. We injected six other rabbits with similar volumes of saline as
      controls. Two weeks after the second injection, we measured micturition
      frequency, bladder weight, response to electrical field stimulation, and response
      to bethanecol in each group. Fat implants were present at the injection site in
      each case 4 weeks after the first injection. Rabbits receiving fat implants had
      increased micturition frequency, increased bladder weight, and increased response
      to bethanecol and field stimulation. Previous studies have demonstrated that
      these changes are characteristic of mild outlet obstruction in rabbits. Injected
      fat can be made to close the urethra and create bladder outlet obstruction in
      rabbits. The short-term success of fat as a bulking agent in this experiment is
      encouraging and suggests the need for longer term studies.

PMID- 7647810
TI  - Blood flow of the urinary bladder: effects of outlet obstruction and correlation
      with bioenergetic metabolism.
AB  - This study investigated the effects of outlet obstruction on blood flow and high
      energy phosphates content in the rabbit urinary bladder. Mild bladder outlet
      obstruction was induced by placing a silicon ring (diameter 7 mm) around the
      bladder neck of each male New Zealand White rabbit (n = 7). Before and
      immediately after inducing obstruction, and 2 weeks later, the bladders were
      emptied and regional blood flow measured using laser Doppler flowmetry (LASERFLO
      BPM2, Vasamedics Inc., St. Paul, Minnesota). Six different areas of each bladder
      were measured, and the average blood flow calculated for each rabbit. Then, the
      animals were sacrificed, the bladder excised, and the tissue content of high
      energy phosphates determined by high performance liquid chromatography (HPLC).
      Six normal male New Zealand White rabbits served as controls. The results can be
      summarized as follows: (1) Before surgery, bladder blood flow was similar in all
      animals (16.3 ml/min/100 g); positioning the silicon ring around the bladder neck
      did not affect blood perfusion, two weeks after the induction of outlet
      obstruction, bladder blood flow was significantly decreased (4.9 ml/min/100 g).
      (2) There was no significant difference between control and obstructed bladders
      in NAD, AMP, or ADP content. However, the obstructed bladders contained
      significantly less phosphocreatine (12.0 vs 21.9 nmol/mg protein) and ATP (4.0
      vs. 6.1 nmol/mg protein) than control bladders. In summary, this study showed
      that urinary bladder blood flow was reduced by outlet obstruction, and the
      reduction in blood flow was associated with decreased tissue high energy
      phosphates content.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7647811
TI  - Biotechnology in Chile (overview).
AB  - This article provides a brief overview of biotechnological activities in Chile.
      The role played by the scientific community is emphasized and aspects of
      technology transfer are commented.

PMID- 7647812
TI  - The evolution of brain size and organization in vertebrates. A program for
      research.
AB  - In vertebrates, brain size variability relates to two main parameters: body size
      and ecological factors (in particular diet and foraging strategy). It has been
      considered by many authors that evolutionary brain growth is a unitary phenomenon
      whose main effect is to increase processing capacity. Alternatively, in this
      paper it is considered that brain growth is significantly associated with higher
      processing capacity only when it occurs associated with ecological circumstances
      (selection of behavioral or perceptual skills). This process is referred to as
      "active" growth. When the brain scales on body size, there is little change in
      processing capacity, and this will be referred to as "passive" growth. I propose
      that these two modes of phylogenetic brain growth relate to different
      developmental/evolutionary processes and are distinguishable at the level of
      adult and developing structure. Shortly, growth due to selection of behavioral
      capacities is associated with more differentiated brains in terms of number of
      areas, connectional rearrangements and cell types. Growth due to scaling of body
      mass produces little brain rearrangements, and many of those that occur relate to
      the maintenance of functions in a larger brain. In addition, active selection of
      brain size is triggered by plastic, ontogenic rearrangements of connectivity in
      the organisms, while passive growth produces the minor rearrangements that take
      place. Finally, I propose a research program oriented to test this model by
      separating the effects of body size and ecological variables in brain
      organization across species.

PMID- 7647813
TI  - Parietal cells contain most of the myosin, filamin and actin present in rat
      gastric glands.
AB  - The association of myosin and a filamin-like protein to the F-actin cytoskeleton
      of parietal cells was studied in the rat gastric mucosa. Myosin and the filamin
      like protein were localized by indirect immunofluorescence microscopy while the
      distribution of actin was established by using FITC-phalloidin. These
      cytoskeletal proteins, concentrated in the parietal cells, changed their
      distribution in correlation with the hydrochloric acid (HCl) secretory state of
      the cells and the appearance of a developed intracellular canaliculus. Thus, in
      resting parietal cells, actin showed a patchy distribution, delimiting the poorly
      developed secretory canaliculi, while myosin and the filamin-like protein
      distributed diffusely over the cytoplasm. In secreting cells, F-actin was
      concentrated in the cytoplasmic projections filling the canalicular lumen, while
      myosin and the filamin-like protein were excluded from this region, concentrating
      in the adjoining cytoplasm. The present results show that myosin and the filamin
      like protein change their association with the secretory membranes in relation to
      the development of the secretory canaliculus of parietal cells. In resting cells,
      both proteins associate with the endocellular secretory membranes. In secreting
      cells, the microvillar projections of the canalicular surface formed by these
      membranes bind F-actin, but exclude myosin and the filamin-like protein.

PMID- 7647814
TI  - Structure of rotavirus particle: interaction of the inner capsid protein VP6 with
      the core polypeptide VP3.
AB  - The structural relationship between VP6 (inner capsid polypeptide) and the viral
      core was studied using chemical cross-linking with dithiobis(succinimidyl
      propionate). Crosslinked single shelled and reconstituted rotavirus particles,
      suggest the existence of a complex organization of VP6 molecules in the inner
      capsid and a direct interaction with the core polypeptide VP3. The inhibition of
      the recovery of RNA polymerase activity associated with the reconstitution of the
      single shelled particle in the presence of antiVP6 monoclonal antibodies
      indicates that a VP6 domain between amino acids 56 and 58 seems to be important
      in viral transcription. A VP6 gene temperature-sensitive mutant (ts G) carrying a
      mutation affecting assembly of single shelled particles was used in
      reconstitution experiments. The mutant was able to recover RNA polymerase
      activity at restrictive temperature. Wild type cores or VP6 were able to
      reconstitute the particle with both the mutant cores and VP6. These results
      suggest the existence of various steps for the assembly of single shelled
      particles, where the VP6-VP3 interaction seems to be important for recovery of
      RNA polymerase activity.

PMID- 7647815
TI  - A fluorescence method to determine picomole amounts of Zn(II) in biological
      systems.
AB  - The formation of complexes between n-(6-methoxy-8-quinolyl)-p-toluensulfonamide
      (TSQ) and Zn(II) in methanol has been used as an analytical procedure for Zn(II)
      determination in biological systems. Using 1 ml cuvettes, the limit of detection
      of the method was approximately 20 pmoles of Zn(II). Linearity between
      fluorescence and zinc concentration was obtained up to approximately 1 microM
      Zn(II). Common multivalent cations present in biological systems like Al3+, Cu2+,
      Fe3+, Ca2+, and Mg2+, interfered with the measurement of Zn(II) only when present
      in excess of 20, 33, 60, 500 and 30,000 times the Zn (II) concentration,
      respectively. In human serum and semen, deproteinization of the samples permitted
      a good correlation between the TSQ method and the total Zn content determined by
      atomic absorption measurements. In rat spermatids, deproteinization and Zn (II)
      determination using the TSQ method gives approximately a 20% underestimation of
      the total Zn (II) content of the cells as compared to atomic absorption
      spectrophotometry. The method gives low resolution of Zn (II) peaks when tested
      as an analytical procedure to measure Zn (II) binding to protein fractions eluted
      during column chromatography.

PMID- 7647816
TI  - Increased sensitivity and accumulation of estradiol in the rat oviduct during
      early pregnancy.
AB  - We have previously reported that a single injection of estradiol-17 beta (E2)
      given on day 3 of pregnancy (P3) is far more effective for accelerating oviductal
      transport in the rat, than treatment given on day 1 (P1). In order to quantify
      this change, dose-response curves were established for six different doses of E2
      (range 0.031 to 1.00 micrograms per animal) given on P1, P2 or P3. In addition, a
      possible mechanism was explored by comparing the plasmatic and oviductal levels
      of E2 between 30 and 180 min following treatment with E2 on P1 or P3. As the
      interval from ovulation to treatment was increased, the transport of a larger
      number of embryos was accelerated and a smaller dose was required. The minimal
      effective dose decreased 30-fold from P1 to P3, the oviducts accumulated 20% to
      90% more E2 on P3 than on P1, tissue levels were 6- to 48-fold higher than plasma
      levels and the latter did not differ between P1 and P3. It is concluded that the
      oviduct exhibits increased sensitivity and responsiveness to E2 on P3 and this is
      associated with greater accumulation of the hormone in the organ, not
      attributable to higher E2 plasma levels.

PMID- 7647817
TI  - Effect of pre- and postnatal retinal deprivation on the striate-peristriate
      cortical connections in the rat.
AB  - The tangential distribution of the striate-peristriate cortical connections in
      normal, postnatally eye enucleated and congenitally anophthalmic rats, was
      studied after a single injection of wheat germ agglutinin conjugated with
      horseradish peroxidase into the striate cortex. The typical normal pattern of
      separate fields in the peristriate cortex is altered in eye enucleated animals,
      in such a way that their areal distribution in the cerebral cortex is increased
      and each field tends to fuse with the adjacent one. This process is more marked
      in anophthalmic animals, a finding that is in agreement with the notion that
      ganglion cells exert their influence before the visual pathway is functional.

PMID- 7647818
TI  - XXIIIrd World Congress of the International Association of Logopedics and
      Phoniatrics. Cairo, Egypt, August 6-10, 1995. Abstracts.

PMID- 7647819
TI  - Total but not bioavailable testosterone is a predictor of central adiposity in
      postmenopausal women.
AB  - OBJECTIVE: In pre and postmenopausal women low levels of sex hormone binding
      globulin (SHBG) have been shown to be associated with a large waist-hip ratio
      (WHR), a measure of visceral adiposity. Previous studies of WHR and testosterone,
      however, have been inconclusive. DESIGN: We examined the prospective association
      between endogenous total and bioavailable testosterone and SHBG levels at
      baseline with WHR measured 12-15 years later in a community-based cohort of older
      women. SETTING: Rancho Bernardo, California. SUBJECTS: 334 postmenopausal women.
      MAIN OUTCOME MEASURES: Endogenous total and bioavailable testosterone and SHBG
      levels and WHR. RESULTS: Only age-adjusted SHBG levels and the testosterone/SHBG
      ratio were associated with BMI. Age-adjusted SHBG levels and total testosterone
      decreased with increasing WHR. Neither measured nor estimated (testosterone/SHBG
      ratio) bioavailable testosterone was associated with WHR before or after
      adjustment for age, BMI, and cigarette smoking. CONCLUSION: These prospective
      data confirm the reported cross-sectional association between SHBG and WHR, but
      show no association with measured bioavailable testosterone or the
      testosterone/SHBG ratio. These findings do not support the premise that androgens
      cause visceral adiposity in postmenopausal women.

PMID- 7647821
TI  - The influence of small changes in the gravitational field on the weight
      regulation in female Wistar rats.
AB  - OBJECTIVE: To determine effect of small gravitational changes on weight
      regulation in female Wistar rats. METHOD AND RESULTS: Rats submitted to moderate
      increases in the gravitational field will lose weight. We increased the g force
      in steps between 1 and 2.5g and found an exponential correlation between weight
      loss and the gravitational field. The weight loss was reversible upon return to
      normal g force. In adult fully grown rats we found a marked 'overshooting' upon
      return to 1g force after a stay at 2g for 5 weeks. CONCLUSION: A hypothesis is
      proposed suggesting that the weight loss and regain represent the effect of
      regulatory mechanisms on the appetite control presumably mediated via impulses
      from the proprioceptive nerves in the extremities.

PMID- 7647820
TI  - The effect of dexfenfluramine on eating habits in a Dutch ambulatory android
      overweight population with an overconsumption of snacks.
AB  - OBJECTIVE: To investigate the effect of the serotonin receptor agonist
      dexfenfluramine on eating habits and weight loss in ambulatory, android type,
      moderately obese patients with an overconsumption of snacks. DESIGN: 9 week,
      randomized, double-blind treatment with either dexfenfluramine (30 mg/day) or
      placebo, without dietary intervention. SETTING: Outpatient clinics of four
      University Hospitals in The Netherlands. SUBJECTS: 112 healthy obese subjects,
      body mass index 28-35 kg/m2, waist-to-hip ratio > or = 1.0 for men and > or = 0.8
      for women, consuming more than five snacks containing in total more than 500
      kcal/day and/or more than 25% of total calorie intake in the form of snacks. MAIN
      OUTCOME MEASURES: Changes in macronutrient composition of the diet, food intake
      (total, at principal meals and in between meals in the form of snacks) and weight
      loss. RESULTS: 104 subjects were included for efficacy analysis. In both the
      dexfenfluramine group (n = 51) and the placebo group (n = 53) the total energy
      intake decreased. The decrease during main meals was significantly greater in the
      dexfenfluramine group for all parameters tested except for simple carbohydrates.
      In between meals the decrease in intake was significantly greater in the
      dexfenfluramine group for total energy intake (P < 0.05) and intake in
      unsaturated fat (P < 0.05). The reported reduction in total food intake in the
      dexfenfluramine group was similarly due to reductions in carbohydrate and fat
      intake. No weight loss was seen in the placebo group. The treated group lost 3.1
      +/- 0.2 kg (P < 0.01). CONCLUSION: Dexfenfluramine effectively reduces the intake
      of carbohydrates as well as fat in ambulatory, non diet restricted android obese
      subjects by reducing food intake during and in between main meals.

PMID- 7647822
TI  - Consistency and change of body mass index and weight. A study on 5967 adult
      Finnish twin pairs.
AB  - OBJECTIVE: To study twin resemblance for weight change (delta wt) and to assess
      the consistency of body mass index (BMI) over 6 years. DESIGN: 6 year follow-up
      based on identical mailed questionnaires in 1975 (baseline) and in 1981 (follow
      up). SUBJECTS: 5967 same-sexed non-pregnant Finnish twin pairs aged 18-54 in 1975
      (1106 male and 862 female monozygotic (MZ) and 2430 male and 1569 female
      dizygotic (DZ) pairs). MAIN OUTCOME MEASURES: Intra-pair correlations of delta wt
      and BMI, estimates of genetic and environmental components of variance of delta
      wt and BMI. RESULTS: Unadjusted mean delta wt was +2.0 (s.d. = 4.6) kg among MZ
      and 2.1 (4.9) kg among DZ male individuals. Corresponding values among MZ and DZ
      female individuals were +1.5 (4.4) kg and +1.7 (4.4) kg, respectively. Age and
      initial BMI together explained 8.0% of the male and 2.3% of the female phenotypic
      variance of delta wt. The intraclass correlations for delta wt (adjusted for age
      and initial BMI) for all pairs were 0.29 and 0.07 for MZ and DZ men and 0.25 and
      0.05 for MZ and DZ women, respectively. The BMI of the twins increased slightly
      during the follow-up compared to the baseline values (23.9 (2.7) for MZ and 24.1
      for DZ men and 23.0 (3.3) for MZ and 23.2 (3.42) for DZ women). The intra-class
      correlations for BMI at baseline (0.69 for MZ and 0.34 for DZ men and 0.67 for MZ
      and 0.29 for DZ women) were almost identical with the correlations at follow-up
      (0.67 for MZ and 0.32 for DZ men and 0.69 for MZ and 0.29 for DZ women). The
      intra-class correlations for both BMI and delta wt were consistently higher among
      pairs living together than among pairs living apart at baseline and at follow-up
      in both zygosity groups (MZ and DZ). Among pairs living apart at baseline, the
      longitudinal model for BMI showed that the correlation between genetic effects at
      baseline and at follow-up was very high (> 0.9 in all age groups among both
      genders). The correlations for environmental effects ranged from 0.50 to 0.67
      during the follow-up period. CONCLUSION: Weight changes in adults over a 6-year
      period appear to be determined by environmental effects rather than genetic
      factors. However, the genetic component in BMI is considerable and stable over
      time. Shared environment is likely to contribute to the resemblance of both delta
      wt and BMI among adult twin pairs, especially among MZ pairs.

PMID- 7647823
TI  - Impact of a moderately energy-restricted diet on energy metabolism and body
      composition in non-obese men.
AB  - OBJECTIVE: Since little information is available on the capacity of the non-obese
      to adapt to a moderate decrease in energy intake, the effect of a 10-week
      moderately energy-restricted diet (ER) on energy expenditure and body composition
      was studied. DESIGN: A controlled intervention study. After a weight-maintaining
      run-in period of 2 weeks, the ER group received a diet that contained 9.2 MJ/day
      on average, i.e. 80% of the energy of their habitual diet (estimated by means of
      a 7-day dietary record) for the next ten weeks while the control group received
      the weight-maintaining diet. SETTING: Subjects continued daily life habits and
      came to the Institute every evening to have dinner and to receive food for the
      next 24 h. SUBJECTS: 24 healthy non-obese, middle-aged men participated. Subjects
      were matched for age and body mass index and randomly assigned to a control group
      (n = 8) or an ER group (n = 16). RESULTS: Average daily metabolic rate (ADMR,
      i.e. total energy expenditure), measured with doubly labeled water in eight
      subjects of the ER group, appeared to be 82.5% of reported energy intake
      resulting in an actual level of energy restriction in these eight subjects of 33%
      on average (range 18-42%), rather than 20%. Subjects in the ER group lost 7.4 +/-
      1.7 kg; 83% of this weight loss was fat mass, 17% was fat-free mass. Subjects in
      the control group lost some weight too (2.1 +/- 1.5 kg). Resting metabolic rate
      (RMR) (MJ/day) decreased in the ER group (P < 0.001). In this group the thyroid
      hormone triiodothyronine (T3) decreased (P < 0.001), while reverse T3 (rT3)
      increased (P < 0.05). ADMR decreased significantly. CONCLUSION: Under conditions
      of a controlled moderately energy-restricted diet in daily life a significant
      weight loss can be induced, similar to that observed after a balanced dietary
      deficit, providing 5 MJ/day. In addition, moderate energy restriction induces a
      decrease in fat-free mass and a fall in RMR.

PMID- 7647824
TI  - Which anthropometric indices of regional adiposity are related to the insulin
      resistance of aging?
AB  - OBJECTIVE: To determine which anthropometric methods of assessing body fat
      distribution are the most predictive of the insulin resistance of aging. DESIGN:
      Commonly used indices of regional adiposity were correlated with whole-body
      insulin sensitivity in 55 men and 29 women (age range 18-80 years). MEASUREMENTS:
      Insulin sensitivity (SI, minimal model), waist and hip girths, waist-to-hip
      ratios, conicity index, skinfolds, body fat percentage, maximal oxygen
      consumption. RESULTS: There was a wide disparity in the strength of relationships
      between commonly used anthropometric indices of fat distribution and whole-body
      insulin sensitivity. In both sexes minimal waist girth, however, was the primary
      variable in multivariate regression analysis, accounting for approximately 37% of
      the variance in SI. CONCLUSION: These findings indicate that anthropometric
      measures of regional adiposity are not interchangeable and/or equivalent when
      attempting to discern relationships between body fat distribution, insulin
      sensitivity, and aging.

PMID- 7647825
TI  - Spontaneous overfeeding with a 'cafeteria diet' in men: effects on 24-hour energy
      expenditure and substrate oxidation.
AB  - OBJECTIVE: To investigate the relationship between obesity and ad libitum food
      intake (quantity and composition) and to assess the impact of ad libitum food
      intake on energy expenditure and macronutrient oxidation. DESIGN: Male volunteers
      were first fed a weight maintaining diet for at least 4 days before selecting
      their food for the next 5 days from two computerized vending machines offering a
      variety of familiar, palatable foods. 24-h energy expenditure (24EE) and
      substrate oxidation were measured in a respiratory chamber on the last day of
      each weight maintenance and ad libitum intake periods. SETTING: Ten day admission
      on a metabolic research ward. SUBJECTS: Thirty-four non-diabetic Pima Indian
      males covering a wide range of body weight and body composition (30 +/- 8 y,
      102.1 +/- 30.2 kg, 34 +/- 9% body fat, mean +/- s.d.). RESULTS: Weight
      maintenance requirements averaged 2913 +/- 342 kcal/d. Energy intake during the
      ad libitum period increased to 4550 +/- 921 kcal/d (12 +/- 1% protein, 40 +/- 4%
      fat, 48 +/- 4% carbohydrate) i.e., a spontaneous overeating by 54 +/- 32% above
      weight maintenance requirement, resulting in a 0.9 +/- 1.0 kg body weight gain.
      Neither the composition of the selected diet nor the degree of overeating was
      associated with physical characteristics, such as body weight and body
      composition. When compared with baseline, spontaneous overeating on day 5 was
      associated with a 396 +/- 233 kcal/d increase in 24EE, a 607 +/- 503 kcal/d
      increase in carbohydrate oxidation, a 214 +/- 392 kcal/d decreased in lipid
      oxidation (P < 0.01), and no change in protein oxidation. Increased carbohydrate
      oxidation correlated with the excess carbohydrate intake (r = 0.69, P = 0.0001)
      accounting for 68 +/- 13% (mean +/- s.e.e.) of the excess, whereas excess fat
      intake was not oxidized. CONCLUSION: In response to spontaneous overfeeding on a
      mixed 'cafeteria diet', excess carbohydrate intake is oxidized, suggesting a
      physiological control of carbohydrate stores, whereas excess fat intake is
      channeled toward fat stores. None of the observed changes were related to indices
      of obesity.

PMID- 7647826
TI  - The effect of a Plantago ovata seed containing preparation on appetite variables,
      nutrient and energy intake.
AB  - OBJECTIVES: Investigation of a Plantago ovata seed containing supplement
      (Plantaginis ovatae semen and testa) to determine its effect on appetite
      variables, nutrient and energy intake in normal subjects. DESIGN: Triple blind
      (subjects, investigators and statisticians) cross-over design. Three, 3-day study
      periods when subjects were given the following treatments in randomised order:
      Plantago ovata preparation (20 g granules with 200 ml water), placebo (20 g
      granules with 200 ml water), or water (200 ml) 3 hs pre-meal and the same dose
      immediately pre-meal. A set meal was given at lunch time after the supplement to
      subjects who had fasted overnight. SETTING: Metabolic unit of King's College
      London. SUBJECTS: Seventeen female subjects, all classified as non-restrained
      eaters. MAIN OUTCOME MEASURES: Visual analogue scales were completely premeal,
      postmeal and at hourly intervals for 3 hs after the meal. All food consumed on
      the meal day, and the following day was weighed. RESULTS: There was a significant
      difference in fullness at 1 h post-meal between Plantago and placebo, and also
      Plantago and water. Total fat intake was significantly lower in g/d and as a
      percentage of energy on the day of the meal after Plantago compared with water.
      CONCLUSIONS: This plantago ovata containing product, which is already taken by
      many people world-wide to control bowel function, may be a useful supplement in
      weight control diets as it affects fat intake, and may have some effect on the
      subjective feeling of fullness.

PMID- 7647827
TI  - Effect of weight loss and body position on pulmonary function and gas exchange
      abnormalities in morbid obesity.
AB  - OBJECTIVE: To determine, whether behavioral management of obesity including very
      low-calorie-diet would produce weight loss enough to improve pulmonary mechanics
      and gas exchange in morbid obesity. DESIGN: Pulmonary function and arterial
      oxygenation were studied before and after weight loss in 11 patients attending a
      group therapy with the program of VLCD for 6 weeks and 16 weeks' behavioral
      intervention. MEASUREMENTS: Spirometry, diffusing capacity, body plethysmograph,
      closing volume and arterial blood gas analyses. RESULTS: The mean initial BMI was
      45.4 kg/m2 (range 39.8-58.7 kg/m2) and decreased to 39.4 kg/m2 (range 31-49.8
      kg/m2) (P < 0.01). Expiratory reserve volume (ERV) and functional residual
      capacity (FRC) improved significantly with weight loss. Closing capacity (CC)
      exceeded FRC in 10 cases of 11 at the initial stage, but after weight loss only
      in three patients. The mean arterial oxygen tension with the patients in supine
      position did not change after weight loss, but standing up improved PaO2
      significantly before and after weight loss. CONCLUSION: The dietary treatment of
      morbid obesity was sufficient to induce improvement in lung volumes, but not
      enough to improve arterial oxygenation, although ventilatory mechanics was
      improved significantly and the tendency to early small airway closure was
      decreased. Hypoxemia was significantly relieved by standing up both before and
      after weight loss.

PMID- 7647828
TI  - Influence of local blood flow on glycerol levels in human adipose tissue.
AB  - DESIGN: The influence of blood flow on adipose tissue glycerol levels was
      investigated in human subcutaneous adipose tissue in situ, with the aid of
      microdialysis of the extracellular water space. The concentration of tissue
      derived glycerol and the escape of ethanol from the dialysis solvent into the
      extracellular space were simultaneously monitored; the latter was used as an
      index of local blood flow around the probe. RESULTS: Selective vasodilation with
      nitroprusside or hydralazine rapidly reduced the concentration of glycerol by 50%
      and at the same time increased the escape of ethanol (P < 0.001). Stimulation of
      local blood flow and lipolysis with the beta-adrenoceptor agonist isoprenaline
      caused an increase in ethanol escape (P = 0.01) and a 100% rise in the dialysate
      glycerol level (P = 0.001). When vasodilation was first induced by nitroprusside,
      the subsequent addition of isoprenaline to the microdialysate perfusate caused no
      change in the concentration of glycerol in adipose tissue but a slight increase
      in ethanol escape. CONCLUSIONS: In conclusion, local blood flow plays an
      important role in the regulation of the glycerol level in human adipose tissue.
      Stimulation of blood flow may under certain conditions decrease the level of
      glycerol in the extracellular space of adipose tissue although the mobilization
      of glycerol from fat cells to this compartment is increased. Thus, changes in
      blood flow and glycerol should be considered together when adipose tissue
      lipolysis is investigated by microdialysis.

PMID- 7647829
TI  - A study of intelligence and personality in children with simple obesity.
AB  - The objective of this study was to investigate differences in measures of
      intelligence and personality between obese and normal-weight children. The
      Wechsler Intelligence Scale (IQ) for Children (revised) and the Eysenck
      Personality Questionnaire (EPQ) were administered to 102 children with simple
      obesity and their controls in a case-controlled design. The mean age of the
      children was 9.8 years and they all attended primary school in Nanjing, PRC. It
      was found that children in the severe obesity category (> 50% overweight) had a
      significantly lower performance IQ score than the controls, and a significantly
      higher EPQ psychoticism score. These differences were not observed in children
      with milder degrees of obesity.

PMID- 7647830
TI  - The 6th European Congress on Obesity. Copenhagen, Denmark, May 31-June 3, 1995.
      Abstracts.

PMID- 7647831
TI  - Clozapine in the back wards.
AB  - Most reports of clozapine in treatment-refractory patients have dealt with
      outpatient and/or relatively less chronic samples. This report focuses on
      clinical outcome in an institutionalized sample, notable for chronicity, poor
      functioning, and representing the extreme segment of the treatment-refractory
      population. We analyzed the data for 50 persistently hospitalized patients
      referred for clozapine treatment in open trials. Dimensions of outcome assessed
      at baseline and periodically thereafter included psychopathology, cognitive
      performance, extrapyramidal side effects (EPS), and patient satisfaction. Certain
      features of clozapine response in institutionalized patients have been
      underemphasized (e.g., reduced use of restraint and seclusion, greater social
      interaction, reduced cost for care). Ninety-four percent of this sample showed
      some form of improvement with clozapine. Improvement ranged from modest (e.g.,
      less EPS) to remarkable (e.g., discharge). An adequate clozapine trial may
      require more than 6 months.

PMID- 7647832
TI  - The course of tics in Tourette syndrome: a 5-year follow-up study.
AB  - The current study was undertaken to explore the course of tics in Gilles de la
      Tourette's syndrome (TS). As part of a prospective 5-year follow-up of non
      clinically based TS subjects who had originally participated in a comprehensive
      research protocol, 23 subjects (ages 11 to 53 years) were reevaluated for tics
      and obsessive-compulsive (OC) characteristics. Three (13%) of the subjects had an
      improvement in total tic symptomatology, while 15 (65.2%) had no change and 5
      (21.7%) worsened. Improvement or worsening was independent of baseline
      developmental age across child, adolescent, and adult subgroups. Complex motor
      tics at baseline predicted complex motor tics and simple phonic tics at follow
      up. Baseline OC and complex motor tics independently predicted subsequent OC and
      complex motor symptoms. Data from the current study provide evidence of the
      stability of tic subtypes over time and developmental period.

PMID- 7647833
TI  - Tourette syndrome: a hereditary neuropsychiatric spectrum disorder.
AB  - The objective was to determine if the high frequency of behavioral problems in
      Tourette syndrome (TS) probands is the result of the pleiotrophic expression of
      the Gts genes or due to ascertainment bias. It was possible to distinguish
      between these two hypotheses by comparing the frequency of these behaviors in
      nonproband relatives with TS to relatives without TS. Twenty behavioral problems
      were prospectively assessed in a consecutive series of 361 TS probands, 113
      nonproband TS relatives, 380 relatives without TS, and 68 controls, by the
      administration of a questionnaire based on the Diagnostic Interview Schedule and
      the DSM-III-R. Significance was set at a very conservative level of p < or =
      .001. Except for problems with smoking, reading and compulsive eating, all other
      behaviors were significantly more common in nonproband TS relatives than in
      relatives without TS. The relatives were also dichotomized on the basis of each
      of the behavioral problems. Regardless of the behavioral trait used, there was a
      higher frequency of all other behaviors in those who were positive versus those
      who were negative for that behavior. Ranking according to the number of behaviors
      that were significant indicated that mania, obsessive-compulsive behaviors and
      schizoid behaviors represented higher degrees of expression of the Gts genes than
      chronic tics. These results indicate that the Gts genes cause a spectrum of
      behavioral disorders in addition to chronic tics, indicate that TS is a
      behavioral spectrum disorder, and emphasize the role of genetic factors in a wide
      range of human behaviors.

PMID- 7647834
TI  - An open-label study of nefazodone in the treatment of depression with and without
      comorbid obsessive compulsive disorder.
AB  - An 8-week open-label study of nefazodone treatment of DSM-III-R major depressive
      episode (MDE) (n = 18) is reported. Nine of 15 individuals completing treatment
      also met DSM-III-R criteria for obsessive compulsive disorder (OCD). A
      significant reduction in depressive and anxiety symptoms was observed in
      treatment completers; no differences were found between those patients with and
      those without comorbid OCD. A trend toward an antiobsessional response was seen
      among those with OCD. The degree of anxiolytic response was found to be
      significantly correlated with the degree of antidepressant response. Nefazodone
      was well tolerated in most patients, with dizziness, joint pain, dry mouth, and
      sedation as the most commonly reported adverse events.

PMID- 7647835
TI  - Bupropion/nortriptyline combination for refractory depression.
AB  - Many patients fail to respond to one or more trials with a single antidepressant.
      In such cases polypharmacy is often necessary and beneficial, although there may
      be an increased risk of complications. Four case reports are presented of
      patients with refractory depression treated successfully with the combination of
      the tricyclic antidepressant nortriptyline and the newer agent bupropion.

PMID- 7647836
TI  - Malignant catatonia--a continuing reality.
AB  - A comprehensive review of the world literature confirms that malignant catatonia
      continues to occur and is reported and discussed in psychiatric community. It is
      associated with affective disorders as well as schizophrenia. The pathophysiology
      is still unclear but most reports suggest a hypodopaminergic state. Its reported
      mortality has declined from 75-100% in the preneuroleptic era to 31% during the
      review period (1986-1992). Bomocriptine, dantrolene, and benzodiazepines have
      been used with success but ECT has been found to be life-saving. The present
      review supports earlier reports that neuroleptics are frequently lethal in some
      patients with malignant catatonia.

PMID- 7647837
TI  - Anticholinergic toxicity masquerading as neuroleptic malignant syndrome: a case
      report and review.
AB  - Patients who present with acute neuropsychiatric syndromes pose difficult
      diagnostic and treatment challenges. A history of psychiatric illness and
      treatment with psychotropic medication may be valuable clues to diagnosis and
      management of such patients. However, this information may also tempt a clinician
      to focus on a premature diagnosis, excluding other important possibilities. A
      case of a 42-year-old male with recurrent psychotic illness who developed an
      abrupt deterioration in mental and physical status is presented. Despite an
      initial good response to physostigmine, he was diagnosed with neuroleptic
      malignant syndrome and did not receive subsequent treatment with cholinesterase
      inhibitors. The patient expired within hours of arriving in the emergency room.
      The postmortem benztropine level was elevated, leading to the attribution of
      death to anticholinergic toxicity. This case serves to illustrate the
      difficulties in distinguishing features of anticholinergic toxicity and
      neuroleptic malignant syndrome.

PMID- 7647838
TI  - An intelligent interactive system for delivering individualized information to
      patients.
AB  - This paper is a report on the first phase of a long-term, interdisciplinary
      project whose goal is to increase the overall effectiveness of physicians' time,
      and thus the quality of health care, by improving the information exchange
      between physicians and patients in clinical settings. We are focusing on patients
      with long-term and chronic conditions, initially on migraine patients, who
      require periodic interaction with their physicians for effective management of
      their condition. We are using medical informatics to focus on the information
      needs of patients, as well as of physicians, and to address problems of
      information exchange. This requires understanding patients' concerns to design an
      appropriate system, and using state-of-the-art artificial intelligence techniques
      to build an interactive explanation system. In contrast to many other knowledge
      based systems, our system's design is based on empirical data on actual
      information needs. We used ethnographic techniques to observe explanations
      actually given in clinic settings, and to conduct interviews with migraine
      sufferers and physicians. Our system has an extensive knowledge base that
      contains both general medical terminology and specific knowledge about migraine,
      such as common trigger factors and symptoms of migraine, the common therapies,
      and the most common effects and side effects of those therapies. The system
      consists of two main components: (a) an interactive history-taking module that
      collects information from patients prior to each visit, builds a patient model,
      and summarizes the patients' status for their physicians; and (b) an intelligent
      explanation module that produces an interactive information sheet containing
      explanations in everyday language that are tailored to individual patients, and
      responds intelligently to follow-up questions about topics covered in the
      information sheet.

PMID- 7647839
TI  - Control theory as a conceptual framework for intensive care monitoring.
AB  - Monitoring patients hospitalized in hemato-oncology departments to undergo
      clinical protocols of therapy is a complex task. The main difficulty arises in
      the management of the oncology protocol as well as in the management of critical
      episodes of acute illness which frequently occur due to high toxicity of the used
      antimitotics. This problem of controlling a patient's condition can be
      conceptualized within the control theory paradigm as the task of controlling a
      process whose state changes over time and can deviate unacceptably from a normal
      range. Upon request of a French clinical department of hemato-oncology, we
      developed an intelligent patient monitor named SEPIA to assist clinicians in this
      task. Following the control theory analogy at the level of knowledge bases
      design, we have modeled the medical knowledge as control information to represent
      the medical actions, and state information is used as feedback control to
      characterize the patient's state. After a general presentation of SEPIA, the
      analogies between control theory actors and SEPIA's components are specified. The
      article then focuses on state variables representation. The data reduction
      process, activated as new data are given to the system, is described. A simulated
      running session is finally presented to illustrate the whole reasoning process.

PMID- 7647840
TI  - An appraisal of INTERNIST-I.
AB  - INTERNIST-I was an expert system designed in the early 1970's to diagnose
      multiple diseases in internal medicine by modelling the behaviour of clinicians.
      Its form and operation are described, and evaluations of the system are surveyed.
      The major result of the project was its knowledge base which has been used in
      successor systems for medical education and clinical use. We also survey the
      effects of the project through these systems, and conclude that the most
      successful of them in the near future is likely to be Quick Medical Reference
      (QMR) when used as an "electronic textbook" of medicine.

PMID- 7647841
TI  - Neuromuscular blockade provides no benefit over adequate sedation in ventilated
      dogs.
AB  - PURPOSE: To investigate the effect of pharmacological paralysis on systemic
      oxygen consumption to determine whether pharmacological paralysis offers a
      physiological benefit over adequate sedation in ventilated animals. METHODS: Nine
      dogs with normal pulmonary function were mechanically ventilated and sedated with
      alpha-chloralose while paralysis was induced with vecuronium. Oxygen consumption
      was determined via indirect calorimeter in each animal repeatedly in the presence
      or absence of paralysis with seven paired observations in each animal. Sixty
      three pairs of data from nine animals were analyzed by analysis of variance with
      correction for multiple comparisons. RESULTS: Oxygen consumption was 4.3% higher
      in the unblocked state compared with the blocked state (5.39 +/- 0.32 v 5.16 +/-
      0.34 mL/kg-min, P < .001). Carbon dioxide production was 3.0% higher in the
      unblocked state compared with the blocked state (4.92 +/- 0.24 v 4.77 +/- 0.23
      mL/kg-min, P < .01). No other physiological effects were noted. CONCLUSIONS:
      Pharmacological paralysis of mechanically ventilated animals with normal
      pulmonary function that are sedated and resting comfortably produces a
      statistically significant reduction in oxygen consumption; however, the magnitude
      of this change is so small that little genuine clinical benefit would be
      anticipated.

PMID- 7647842
TI  - Strong ion gap: a methodology for exploring unexplained anions.
AB  - PURPOSE: This paper describes the calculation of the strong ion gap (SIG), a
      physical chemical methodology similar to the anion gap (AG), as a measure of the
      anion/cation balance exclusive of sodium, potassium, chloride, and bicarbonate.
      We compared the SIG and AG methodologies in three groups of subjects with and
      without unexplained anions. These groups were (1) healthy volunteers with
      hyperlacticemia during exercise; (2) intensive care unit (ICU) patients with
      sepsis; and (3) ICU patients with severe liver disease. METHODS: The SIG, AG, and
      corrected AG (AGc) were calculated for each group from data available in the
      original reports (groups 1 and 2) and by retrospective chart review (group 3).
      RESULTS: The SIG correlated poorly with the AG in group 2, whereas no correlation
      was seen in groups 1 and 3. The AGc correlated with SIG in all three groups (r =
      .99, .93, and .91 respectively; P < .01 for each group). Although the AG was
      similar, the SIG differed for each group. Group 1 had levels of SIG near zero,
      and groups 2 and 3 had mean SIG's of 4.80 +/- 4.67 mEq/L and 9.60 +/- 6.43 mEq/L
      respectively. The composition of the anion gap differed markedly among subject
      types. CONCLUSIONS: The SIG correlates with the AG once corrected for all known
      anions. The SIG technique can detect unknown anions in a patient population known
      to have them and does not detect unknown anions in healthy volunteers during
      exercise. This test detects large amounts of unknown anions in some patients with
      sepsis or liver disease. Therefore, the test is both sensitive and specific in
      characterizing metabolic acidosis.

PMID- 7647843
TI  - Endocrine changes and metabolic responses in a validated canine brain death
      model.
AB  - PURPOSE: Endocrinologic and metabolic changes after brain death (BD) have not yet
      been investigated in a validated animal model. Therefore, the effects of BD on
      hormonal and metabolic function were studied in 10 dogs (23 to 31 kg). METHODS:
      BD was induced by intracranial pressure increase and validated
      neuropathologically. Plasma concentrations of pituitary, thyroid, adrenal, and
      pancreatic hormones were measured pre/post BD. The results are expressed as mean
      (+/- SEM). RESULTS: A Cushing reflex and diabetes insipidus occurred after BD.
      Elevated catecholamine levels were documented after 15 minutes whereas the
      pituitary gland hormones vasopressin and adrenocorticotrophic hormone (ACTH)
      decreased significantly after 15 and 45 minutes of BD respectively. Thyroxine,
      triiodothyronine, and glucagon decreased significantly (P < .01) from 0.58 ng/mL
      (+/- 0.05), 2.20 micrograms/dL (+/- 0.15), and 49.7 pg/mL (+/- 9.1) respectively
      to 0.34 ng/mL (+/- 0.03), 1.14 micrograms/dL (+/- 1.14), and 6.9 pg/mL (+/- 1.4)
      respectively 420 minutes after BD. The hematocrit increased significantly after
      BD and declined toward the end of all experiments. Metabolic acidosis occurred
      immediately after BD and at the end of the experiments. CONCLUSIONS: In a simple,
      reproducible, and reliable animal model of BD, a catecholamine storm, vasopressin
      and ACTH cessation, and diabetes insipidus were consistent findings. The decrease
      in cortisol and vasopressin levels warrant consideration of hormonal therapy.

PMID- 7647844
TI  - Serum neopterin and soluble interleukin-2 receptor for prediction of a shock
      state in gram-negative sepsis.
AB  - PURPOSE: This study aimed to investigate the predictive value of neopterin and
      soluble interleukin-2 (IL-2) receptor for shock occurrence in gram-negative
      sepsis. METHODS: We examined 57 patients admitted to an intensive care unit with
      gram-negative sepsis diagnosed according to preestablished criteria. Blood
      samples were collected every 24 hours and neopterin and soluble IL-2 receptor
      were measured by using commercially available test kits. To judge the predictive
      significance of these analyses the Cox proportional hazards regression model was
      used. RESULTS: Both neopterin (P < .05) and soluble IL-2 receptor (P < .01) were
      identified as significant predictors of a shock state, but the prognostic
      strength of neopterin exceeded that of soluble IL-2 receptor. To further assess
      if other factors could interfere with the predictive significance of both
      compounds, we also investigated other clinical and laboratory variables but these
      candidate predictors did not contribute any additional significant predictive
      information. CONCLUSION: The measurement of serum neopterin and soluble IL-2
      receptor concentrations has predictability for identifying patients with gram
      negative sepsis at risk for progression toward the syndrome of septic shock.

PMID- 7647845
TI  - Do synthetic adrenergic agents interfere with the measurement of endogenous
      plasma catecholamine concentrations?
AB  - PURPOSE: It is common to administer synthetic sympathomimetic and sympatholytic
      agents in the intensive care unit and operating room. The present study examines
      whether such agents, as well as the products of catecholamine metabolism,
      interfere with the quantitation of endogenous catecholamines by high-performance
      liquid chromatography. METHODS: Samples of drugs and metabolites were assayed
      before and after alumina extraction and their relative retention times were
      compared with dopamine, norepinephrine, and epinephrine relative retention times.
      Blood samples from patients receiving these drugs were also assayed for their
      interferences with catecholamine determination. RESULTS: Phenylephrine interfered
      with the quantitation of epinephrine. Isoproterenol's peak was so delayed it
      appeared in the following chromatogram. Dobutamine had two small peaks in vitro,
      whereas in the patient samples only one peak was identified; the other was
      probably masked by the dopamine peak. Labetalol had one peak when the pure drug
      was assayed but multiple peaks in patient samples, that were probably caused by
      metabolites of labetalol. CONCLUSION: Synthetic adrenergic agents and
      catecholamine metabolites can potentially interfere with the quantitation of the
      endogenous catecholamines. Thus, it is important to examine whether such
      interference occurs when conducting high-performance liquid chromatography
      assays.

PMID- 7647846
TI  - Applied molecular biology: the molecular mechanisms of sepsis.

PMID- 7647847
TI  - Molecular mechanisms of sepsis: molecular biology of the cell.
AB  - Complex and interrelated biological processes are at work in the expression of
      the host response to sepsis. To a large degree, these processes reflect drastic
      changes in the molecular workings of cells of the body. The protean nature of
      sepsis reflects this molecular adaptation. Studies are continuing to accrue that
      describe aspects of this process in tissue culture, animal models, and man.
      However, without an understanding of the basic mechanisms of molecular biology,
      the understanding of this important and expanding literature is limited. This
      review describes the basic molecular processes involved in replication of
      deoxyribonucleic acid (DNA) and transcription of DNA to ribonucleic acid (RNA) in
      the nucleus, translation of messenger RNA into proteins and the posttranslational
      modifications of these proteins in the cytoplasm. It uses the process of
      endotoxin-induced cellular activation as its model and highlights important
      aspects of DNA promoter and enhancer processes in this activation. Specific
      examples of known promoter genes and genomic translation are described. This
      review serves as a "primer" for the subsequent three review articles in this
      series that will follow it in preceding issues.

PMID- 7647848
TI  - Cryopreservation and freeze-drying protocols. Introduction.

PMID- 7647849
TI  - A two-step or equilibrium freezing procedure for the cryopreservation of plant
      cell suspensions.

PMID- 7647851
TI  - Cryopreservation of shoot-tips and meristems.

PMID- 7647850
TI  - Vitrification of plant cell suspensions.

PMID- 7647852
TI  - Cryopreservation of seeds.

PMID- 7647853
TI  - Cryopreservation of the sperm of the Pacific oyster Crassostrea gigas.

PMID- 7647854
TI  - Cryopreservation of fish spermatozoa.

PMID- 7647856
TI  - Cryopreservation of animal and human cell lines.

PMID- 7647855
TI  - Cryopreservation of avian spermatozoa.

PMID- 7647857
TI  - Cryopreservation of semen from domestic livestock.

PMID- 7647858
TI  - Cryopreservation of mammalian embryos. Slow cooling.

PMID- 7647859
TI  - Freeze-drying and cryopreservation of bacteria.

PMID- 7647860
TI  - Cryopreservation of mammalian embryos. Vitrification.

PMID- 7647861
TI  - Cryopreservation of human gametes.

PMID- 7647862
TI  - Cryopreservation of human red blood cells.

PMID- 7647863
TI  - Freeze-drying of yeasts.

PMID- 7647864
TI  - Cryopreservation of yeast cultures.

PMID- 7647865
TI  - Cryopreservation and freeze-drying of fungi.

PMID- 7647866
TI  - Cryopreservation of pathogenic and nonpathogenic free-living amoebae.

PMID- 7647867
TI  - Virus cryopreservation and storage.

PMID- 7647868
TI  - Long-term cryopreservation of thylakoid membranes.

PMID- 7647869
TI  - Cryopreservation of algae.

PMID- 7647870
TI  - Cryopreservation of plant protoplasts.

PMID- 7647871
TI  - [Oncologic nursing in this time of ambulatory care].

PMID- 7647872
TI  - [Repertoire of nursing protocols in the care of diabetic patients. Interview by
      Suzi Toutant].

PMID- 7647873
TI  - [CII and CMDP: reflecting the professional relations between nurses and
      physicians. Interview by Suzanne Blanchet].

PMID- 7647874
TI  - [Jean Bilodeau: pioneer in home respiratory care. Interview by Suzanne Blanchet].

PMID- 7647875
TI  - [Support and education in the key elements for couples treated for fertility].

PMID- 7647876
TI  - [Does humor have a place in the helping relationship].

PMID- 7647877
TI  - The pros and cons of ambulatory care.

PMID- 7647878
TI  - [Fighting solitude in the elderly with pet therapy].

PMID- 7647880
TI  - The Charleston policy on cocaine use during pregnancy: a cautionary tale.

PMID- 7647879
TI  - [Staying at home despite urinary incontinence].

PMID- 7647881
TI  - Dethroning choice: analogy, personhood, and the new reproductive technologies.

PMID- 7647882
TI  - Bargaining about futility.

PMID- 7647883
TI  - Critical interests and sources of familial decision-making authority for
      incapacitated patients.

PMID- 7647884
TI  - The Oregonian ICU: multitiered monetarized morality in health insurance law.

PMID- 7647885
TI  - Does the ADA provide protection against discrimination on the basis of genotype?

PMID- 7647886
TI  - Should we hold the (germ) line?

PMID- 7647887
TI  - An economic analysis of the joint purchasing safety zone.

PMID- 7647888
TI  - Review essay: the high cost of administration in health care: part of the problem
      or part of the solution?

PMID- 7647889
TI  - Ethics consultation: refusal of beneficial treatment by a surrogate decision
      maker.

PMID- 7647890
TI  - California court expands physicians' duty to warn HIV patients.

PMID- 7647891
TI  - Incorporating new medical information into clinical practice.

PMID- 7647892
TI  - Spatial heterogeneity of mucosal blood flow during ischemia-reperfusion injury of
      rat stomach investigated by laser Doppler perfusion imaging.
AB  - Spatial alterations in blood flow during the development of mucosal injury
      induced by ischemia-reperfusion in rats were determined with a two-dimensional
      laser Doppler tissue perfusion imager. The rats were anesthetized with
      pentobarbital, and the stomach was exteriorized on a stage; the mucosa was then
      sequentially scanned. The mucosa was constantly superfused with 0.1 N HCl in
      physiological saline. Systemic arterial pressure was continuously monitored and
      blood was stepwisely withdrawn from the femoral artery by 20-mmHg stage and then
      maintained at 20 mmHg for 20 min. The shed blood was reinfused and the stomach
      was removed 30 min later. Under control conditions, the average perfusion of the
      forestomach was usually greater than that in the glandular stomach. When systemic
      blood pressure was stepwisely decreased, the extent of decrease in the mucosal
      blood perfusion unit was always greater than that in systemic blood pressure, but
      mucosal perfusion appeared to be uniformly decreased throughout the stomach. Ten
      min after reperfusion, a hypoperfused area began to appear in the corpus near the
      greater curvature, and this area subsequently increased. The area of ulcer
      formation corresponded with the hypoperfused area in the gastric mucosa 30 min
      after reperfusion. Pretreatment with CV-6209, a platelet-activating factor
      antagonist, significantly attenuated the hypoperfusion induced by reperfusion and
      also prevented gastric mucosal damage. Our results suggest that hypoperfusion in
      the mucosal microcirculation is indeed an important factor contributing to the
      localized occurrence of gastric mucosal lesions and that the laser Doppler
      perfusion imager is useful for the detection of local hypoperfused areas in the
      gastric mucosa.

PMID- 7647893
TI  - Morphological changes in gastric carcinoma with progression.
AB  - By combining morphological two indices, namely, (1) the degree of differentiation
      of glandular tubules (well or poor) and (2) the amount of intracellular mucus
      (rich or poor), we previously classified histological types of gastric carcinoma
      into four types. Using this histological classification, we studied the
      morphological changes of gastric carcinoma according to extra-gastric invasion in
      200 autopsy and 200 resected cases. In cases in which the predominant
      histological type in the lamina propria was "tubular differentiation--well, mucus
      in cytoplasm--poor," there was a greater incidence of co-existence with other
      histological types. In many of these cases, the predominant histological findings
      changed to "tubular differentiation--poor" in the subserosa, followed by direct
      invasion into neighboring extra-gastric tissues. In all cases in which the
      predominant histological type in the lamina propria was "tubular differentiation-
      poor," the predominant histological type in the subserosa was also "tubular
      differentiation--poor." To understand the mode of extension of gastric carcinoma
      in relation to the histological type, we must consider not only the
      characteristics of the predominant histological types of carcinoma but also those
      of co-existing types, especially in cases of "tubular differentiation--well,
      mucus in cytoplasm--poor."

PMID- 7647894
TI  - Serum antibody against Helicobacter pylori assayed by a new capture ELISA.
AB  - We developed a highly specific detection technique for serum antibody, using a
      monoclonal antibody to a specific antigen of Helicobacter pylori. A monoclonal
      antibody preparation that reacted with the 54-kDa molecule of H. pylori antigens
      was obtained. Using this preparation, an antigen-capture enzyme-linked
      immunosorbent assay (ELISA) was established by fixation of the monoclonal
      antibody, followed by reaction with sonicated whole cell antigens. The serum
      antibody titers of patients with gastritis and peptic ulcers were significantly
      higher than control titers, and the antibody titer correlated with the
      histological severity of gastritis. Patients positive for H. pylori by bacterial
      culture had higher titers than H. pylori-negative patients. Our new ELISA may be
      useful for the diagnosis of H. pylori infections and for evaluation of the
      severity of gastric inflammation.

PMID- 7647896
TI  - Use of acetylcholine (Ach) for spreading metaphase chromosomes and application to
      the cytogenetic analysis of human stomach cancers.
AB  - Cytogenetic studies of biopsy specimens endoscopically obtained from gastric
      cancers were performed in our laboratory. The necessity for well-spread
      chromosomes for analysis has resulted in the development of a new technique, in
      which culture medium containing acetylcholine (Ach) is used; with this new
      technique, the number of metaphases of analyzable karyotypes was significantly
      increased (P < 0.01 compared with a previous method in which Ach was not used).
      The mean ratio of metaphase numbers of analyzable karyotypes in four cases in
      which Ach was used was 38.1 +/- 8.1%, a value more than four times the number in
      the seven cases in which Ach was not used. It is possible that Ach may decrease
      the viscosity of the cytoplasm in gastric cancer cells by disrupting
      microfilaments.

PMID- 7647895
TI  - Wound healing of acetic acid-induced gastric ulcer in rats and the effects of
      cimetidine and calcitonin, with special reference to prolylhydroxylase and
      collagenase enzyme activity.
AB  - The healing of acetic acid-induced gastric ulcer in rats and the effects of
      cimetidine and calcitonin were investigated with reference to the enzyme activity
      of both prolylhydroxylase and collagenase as related to histological findings.
      The rats were observed by endoscopy on the 3rd day after the subserosal injection
      of acetic acid; rats with ulcers were divided into three groups: non-treated, and
      cimetidine- and calcitonin-treated. The latter two groups were treated for 7
      days. Prolylhydroxylase activity in active ulcers in the non-treated group was
      slightly higher on the 3rd day and significantly higher on the 10th day than the
      activity in control rats that had received subserosal injections of physiological
      saline solution on the respective days. In non-treated rats, the healed ulcer on
      the 10th day showed lower prolylhydroxylase activity than that in the active
      ulcer on the same day. Cimetidine did not affect prolylhydroxylase activity, but,
      with calcitonin, there was higher prolylhydroxylase activity in the healed than
      in the active ulcer, although the difference was not significant. Interstitial
      collagenase showed the highest activity on the 3rd day and decreased on the 10th
      day in non-treated rats. Collagenase activity was higher in the cimetidine
      treated group, than that in the non-treated group, and numerous peroxidase
      positive granulocytes were seen in the mucosa and submucosa. Calcitonin did not
      affect collagenase activity. The participation of both enzymes is indispensable
      in the healing process and the effects of anti-ulcer agents on these enzymes must
      be considered.

PMID- 7647897
TI  - Lipid composition and fatty acid analysis of Helicobacter pylori.
AB  - Lipids extracted from Helicobacter pylori were separated into lipid classes by
      thin-layer chromatography. Simple H. pylori lipids consisted of cholesterol
      esters, triglycerides, free fatty acids, cholesterol, diacylglycerols, and
      monoacylglycerols. Fatty acids were released from each lipid class by acid
      methanolysis, and analyzed by gas liquid chromatography and mass spectrometry.
      Unique methoxy fatty acids, including 11-methoxy heptadecanoic and 11-methoxy
      nonadecanoic acids, were the major components of the cholesterol esters and
      triglycerides. The predominance of methoxy fatty acids in the cholesterol esters
      of H. pylori may contribute to the acid-resistant characteristic of this
      bacillus.

PMID- 7647898
TI  - Omeprazole-amoxycillin therapy for eradication of Helicobacter pylori in duodenal
      ulcer bleeding: preliminary results of a pilot study.
AB  - Thirty-five patients with duodenal ulcer bleeding and Helicobacter pylori
      colonization were assigned to receive 2 x 20 mg omeprazole and 3 x 750 mg
      amoxycillin daily for 2 weeks. Eradication was defined as no evidence of H.
      pylori infection by urease test and by histology 4 weeks after completion of
      therapy. Two patients were lost to follow up. All ulcers healed completely (100%
      ulcer healing rate). Twenty-nine out of the 33 patients were H. pylori-negative
      (87.9% eradication rate). Three patients complained of typical side effects of
      amoxycillin (9.1% side effect rate). The patients were prospectively followed for
      12 months. After ulcer healing, no maintenance therapy was given. One of the 29
      patients in whom H. pylori eradication had been successful suffered a second
      ulcer hemorrhage with H. pylori reinfection (3.4% relapse rate of ulcer
      bleeding), and this was managed endoscopically. Recurrent ulcer hemorrhage
      occurred in 2 out of 4 H. pylori-resistant patients. At the end of the follow-up
      period, of the patients in whom H. pylori eradication had been initially
      successful, only the patient with re-bleeding remained reinfected. The 4 H.
      pylori-resistant patients showed persistent H. pylori colonization. In
      conclusion, omeprazole plus amoxycillin is a safe and effective treatment for
      eradicating H. pylori; this treatment reduces the relapse rate of duodenal ulcer
      bleeding.

PMID- 7647899
TI  - Leukocytapheresis therapy, performed with leukocyte removal filter, for
      inflammatory bowel disease.
AB  - Leukocytapheresis (LCAP), performed with a leukocyte removal filter, was
      administered five times, at 1-week intervals, for 5 weeks of intensive therapy
      and five times, at approximately 1-month intervals, for approximately 5 months of
      maintenance therapy, to 13 patients with inflammatory bowel disease (IBD)
      diagnosed as ulcerative colitis (UC) in 8 and Crohn's disease (CD) in 5. Clinical
      and blood examinations showed no side effects in any of the patients. During the
      intensive therapy, excellent or moderate clinical response was recognized in 11
      of the 13 patients (84.6%), of whom 6 had a dramatic response; the excellent or
      moderate clinical response continued throughout the maintenance therapy in 8 of
      the patients (61.5%). Flow cytometry showed that the patients who had improved
      generally had high values for percentages of HLADR+, HLADR+CD3+, and HLADR+CD8+
      cells before the first LCAP, and that these values and the C-reactive protein
      levels and erythrocyte sedimentation rates had decreased to the normal range by
      the end of both intensive and maintenance therapy. In the patients who showed
      poor response, in contrast, all the above values had been at or near normal
      before the initial LCAP administration. The clinical improvement in the absence
      of any additional medical treatment suggests that LCAP has the capacity to
      influence the causal mechanism(s) of IBD and that IBD is strongly associated with
      the cell-mediated immune response.

PMID- 7647901
TI  - The ratio of reduced glutathione/oxidized glutathione is maintained in the liver
      during short-term hepatic hypoxia.
AB  - Controversy persists as to whether reperfusion-induced injuries actually occur in
      the hepatocyte. The liver is the major source of glutathione, a scavenger of
      hydrogen peroxide. The aim of this study was to evaluate the sensitivity of the
      ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG) [GSH:GSSG] as
      an index of hepatic metabolic stress. A total of 121 rats were studied. The
      superior mesenteric vein (SMV) was occluded for 30 min, and this was followed by
      0, 10, or 120 min of reperfusion. Total glutathione and GSSG levels in the liver,
      bile, and plasma were quantified, using glutathione reductase-coupled enzymatic
      assays. Results indicated that the hepatic GSH/GSSG ratio was maintained after an
      occlusion of the SMV, despite a decrease in adenosine triphosphate (ATP) level
      and energy charge potential. However, plasma levels of total glutathione and GSSG
      in the inferior vena cava increased after SMV occlusion and continued to increase
      after reperfusion. Biliary GSSG efflux decreased during 30-min occlusion of the
      SMV, and remained low even after reperfusion. The liver maintains homeostasis
      despite a decrease in biliary GSSG efflux, probably by secreting excess GSSG into
      the hepatic vein when the SMV is occluded. We conclude that the total amount of
      glutathione and GSSG in the plasma is directly correlated with oxidative stress
      in the liver.

PMID- 7647900
TI  - Immunohistochemical study of gamma delta T cell receptor-positive cells in the
      capsular region of hepatocellular carcinoma: possible role in defense against
      expansion of carcinoma in the liver.
AB  - The localization and distribution of gamma delta T cell receptor (TCR)-positive
      cells (gamma delta T cells) in hepatocellular carcinoma capsules was investigated
      immunohistochemically at both light and electron microscopic levels. Most of the
      mononuclear cells infiltrating the tumor capsules were CD3-positive. Together
      with gamma delta T cells, they were significantly increased in the tumor capsules
      compared to amounts in the fibrous septa in non-cancerous cirrhotic areas of the
      same liver, and compared to amounts in the liver of patients with cirrhosis.
      Phenotypic characterization by the two-color double-staining technique showed
      that CD8/gamma delta cells were significantly increased in the tumor capsule, and
      that more than one-third of gamma delta TCR-positive cells also expressed the
      CD56 antigen. Morphological observation revealed that large gamma delta T cells
      were increased in number in the tumor capsule and that the cytoplasm of these
      cells contained multivesicular bodies and dense granules. These morphological
      features were similar to those of large granular lymphocytes, and most of the
      gamma delta T cells were also positive for BB3. This suggests that extrathymic
      maturation of gamma delta T cells occurs in the tumor capsule, and that these
      gamma delta T cells may have a cytolytic effect on tumor cells, as shown in large
      granular lymphocytes; further, the results suggest that these cells may play a
      role in the defense against tumor expansion.

PMID- 7647902
TI  - Effect of biotin on ammonia intoxication in rats and mice.
AB  - The effects of biotin on ammonia concentration in blood and brain were evaluated
      in hyperammonemic rats and mice. Rats were injected with 5 mmol/kg BW of ammonium
      acetate, and mice were injected with 10 mmol/kg BW. Increases in blood ammonia
      levels in rats 15-30 min after ammonia loading were prevented by treatment with
      0.2 ml/100 g BW of biotin or 0.04 ml/100 g BW of arginine-glutamate with
      statistical significance. Blood ammonia levels after ammonia loading were lower,
      although not significantly, in the arginine glutamate-treated rats than in the
      biotin-treated animals. In mice also, increases in blood and brain ammonia levels
      after ammonia loading were prevented by the administration of biotin. The
      decrease in brain glutamate and aspartate after ammonia loading was lower and the
      brain glutamine level was higher in biotin-treated mice than in the controls.
      These findings indicate the protective effect of biotin against ammonia
      intoxication.

PMID- 7647903
TI  - Study of repeated arterial infusion chemotherapy with a subcutaneously implanted
      reservoir for advanced hepatocellular carcinoma.
AB  - We performed repeated arterial infusion chemotherapy (RAIC) in 114 advanced
      hepatocellular carcinoma (HCC) patients, using a subcutaneous reservoir implanted
      under ultrasonic guidance. In 60 patients, this was the initial therapy for the
      primary tumor and the other 54 patients being treated for recurrent tumor. One
      hundred and seventy-one patients with advanced HCC who had been treated by
      transcatheter arterial embolization (TAE) or single bolus arterial infusion
      chemotherapy before RAIC was available served as historical controls. In 97
      patients, anticancer agents (4'-epidoxorubicin or acurarubicin) and Lipiodol
      emulsion were used, and in 17, anticancer agents alone were given. The response
      rates were 39.2% in the Lipiodol group and 17.6% in the non-Lipiodol group. The
      dose of Lipiodol and the degree of liver invasion were the most important factors
      influencing the response rate. The 1-, 2-, and 3-year survival rates were 55.0%,
      30.9%, and 21.2%, respectively. The long-termsurvival was compared in relation to
      Child's classification and the presence or absence of portal vein tumor
      thrombosis (PVTT). In non-PVTT patients, the results of initial therapy and
      therapy for recurrence were similar, but recurrent Child's C patients showed a
      poorer prognosis. In PVTT patients, initial therapy had a better prognosis than
      treatment for recurrence, but initial Child's C patients had a poor long
      termprognosis. During the observation period, no severe complications were
      encountered, but in Child's C patients, hepatic function sometimes deteriorated.
      Compared with the results in the 171 controls, RAIC was more useful for advanced
      HCC as initial therapy, and it was also beneficial for the treatment of
      recurrence after TAE.

PMID- 7647904
TI  - Interferon treatment of chronic hepatitis C in patients with hemophilia or von
      Willebrand's disease in Japan.
AB  - Seven patients with chronic hepatitis C, six hemophiliacs and a patient with von
      Willebrand's disease, were treated with interferon-alpha (IFN-alpha). Either 9 MU
      of recombinant IFN-alpha 2a or 3 MU of lymphoblastoid alpha-IFN was administered
      daily for 2 weeks and then three times a week for 22 weeks. Liver histology,
      hepatitis C virus (HCV) genotypes, and HCV-RNA levels in sera were investigated
      in all of the patients before IFN therapy was instituted. Liver histology was
      classified by the European classification. HCV genotyping conformed to the so
      called Okamoto's classification. HCV-RNA levels in sera were quantitated by
      competitive polymerase chain reaction, using mutant RNA. Liver histology, HCV
      genotype, and serum HCV-RNA level (copies/ml) in each patient were: patient 1,
      chronic persistent hepatitis, type II, 3 x 10(3) respectively; patient 2, chronic
      active hepatitis (CAH) 2a, type III, 6 x 10(4); patient 3, CAH2a, type IV, 2 x
      10(5); patient 4, CAH2b, type I, 2 x 10(7); patient 5, CAH2b, type II, 8 x 10(4);
      patient 6, CAH2b, type III, 7 x 10(6); and patient 7, CAH2b, type IV, 1 x 10(7).
      Sustained elimination of HCV was achieved in patient 3 and temporary elimination
      was achieved in patients 1 and 2. The other patients showed persistent HCV-RNA
      positivity in sera both during and after IFN treatment. Poor responsiveness to
      IFN was observed in patients with relatively progressive liver histology and high
      levels of HCV viremia.

PMID- 7647905
TI  - Effects of serine protease inhibitors on accumulation of polymorphonuclear
      leukocytes in the lung induced by acute pancreatitis in rats.
AB  - The administration of a high-dose of a serine protease inhibitor is recommended
      in patients complicated by multiple organ failure (MOF), including adult
      respiratory distress syndrome (ARDS), induced by acute pancreatitis. The
      accumulation of polymorphonuclear leukocytes (PMN) in affected organs is
      considered to be one of the causative factors of MOF. Adhesion to endothelial
      cells (EC), via adhesion molecules, and the transendothelial migration of PMN is
      closely associated with the accumulation of PMN. We examined the effects of two
      serine protease inhibitors, ulinastatin (UT) and gabexate mesilate (GM), on EC
      PMN adhesion and transendothelial migration in human umbilical vein EC and 51Cr
      labeled PMN in vitro. EC-PMN adhesion, and the expression of intercellular
      adhesion molecule-1 (ICAM-1) and endothelial cell adhesion molecule-1 (ELAM-1) on
      EC induced by IL-1 beta and TNF alpha, were reduced by the pretreatment of EC
      with these inhibitors. The transendothelial migration of PMN stimulated by IL-8
      was also inhibited by pretreating PMN with UT or GM. We also examined whether
      these inhibitors reduced PMN accumulation in the lung in rats with acute
      pancreatitis induced by a closed duodenal loop. The myeloperoxidase activity in
      and histological findings of the lung suggested that UT and GM reduced PMN
      accumulation. In conclusion, serine protease inhibitors may inhibit PMN
      accumulation in ARDS due to acute pancreatitis.

PMID- 7647906
TI  - A case of gastric antral vascular ectasia--increase of neuroendocrine cells in
      the antrum.
AB  - We report an 82-year-old woman with severe iron deficiency anemia who was found
      to have gastric antral vascular ectasia (GAVE). As she required repeated blood
      transfusion for the anemia and did not respond to various medical treatments, she
      was referred for antrectomy. The pathogenesis of GAVE is still obscure and may
      involve many factors. In our patient, immunohistochemical studies of the resected
      stomach disclosed a marked increase of neuroendocrine cells. The majority of
      these hyperplastic neuroendocrine cells, furthermore, showed immunoreactivity for
      5-hydroxytryptamine (serotonin). These findings suggest that neuroendocrine
      mediators, serotonin in particular, may have been responsible for the local
      vasodilation.

PMID- 7647908
TI  - Resected case of carcinoid tumor of the liver metastatic from the breast.
AB  - Carcinoid tumor metastatic to the liver from the breast is very unusual. We
      report a rare case in which the patient underwent curative resection for
      metastatic lesions to the liver. She had undergone a modified radical mastectomy
      more than 1 year previously for breast cancer. Recently, it was found that plasma
      levels of carcinoembryonic antigen (CEA) was elevated, and abdominal
      ultrasonography detected a liver tumor. The patient underwent a lateral
      segmentectomy of the liver, resulting in normalization of plasma CEA levels. The
      resected specimen was diagnosed as carcinoid tumor by histological,
      immunohistochemical, and ultrastructural microscopic studies. Re-examination of
      the breast tumor proved it to be the primary carcinoid.

PMID- 7647907
TI  - Hepatic failure in a case of multiple myeloma-associated amyloidosis (kappa-AL)
AB  - We report a case of kappa-AL amyloidosis which rapidly developed hepatic failure
      in a 79-year-old Japanese female who was admitted to our hospital because of
      abdominal distension and loss of appetite. Laboratory examination revealed a
      marked deterioration of liver function with cholestasis and monoclonal
      gammapathy. At the time that the diagnosis of IgG-kappa type multiple myeloma was
      made, jaundice was advanced, with continuous gastrointestinal bleeding. The
      patient died of hepatic failure 2 weeks after admission. Needle biopsy of the
      liver revealed a diffuse, massive deposition of amyloid protein.

PMID- 7647909
TI  - Functional liver imaging with asialoglycoprotein receptors and serum hyaluronate
      in a patient with amyloidosis.
AB  - A 47-year-old man with primary amyloidosis was admitted with abdominal pain. A
      new radionuclide liver imaging technique using Technetium-99m diethylenetriamine
      pentaacetic acid-galactosyl human serum albumin, was performed and the serum
      hyaluronate concentration was measured. Although ordinary laboratory tests
      revealed only slight abnormalities, the uptake of the radiolabelled ligand for
      hepatocyte asialo-glycoprotein receptors was decreased, and marked hepatomegaly
      was revealed. Furthermore, the serum hyaluronate level was elevated. Histological
      examination of a hepatic needle biopsy specimen revealed a marked deposition of
      amyloid in the hepatic perisinusoidal spaces. These results indicate that this
      new radionuclide liver imaging technique (using Technetium-99m diethylenetriamine
      pentaacetic acid-galactosyl human serum albumin) and the measurement of serum
      hyaluronate may be useful supplementary tools for identifying amyloid deposition
      in the hepatic perisinusoidal spaces in patients with amyloidosis.

PMID- 7647910
TI  - A case of gallbladder cancer associated with a common bile duct neuroma, and a
      cystic lesion of the liver with histologic findings similar to those of an
      inflammatory pseudotumor.
AB  - We report a rare case of gallbladder cancer associated with a common bile duct
      neuroma, and a cystic liver lesion with histologic findings similar to an
      inflammatory pseudotumor, in a patient who had had no previous abdominal surgery.
      The patient was a 62-year-old man whose major complaint was fever.
      Ultrasonography and a computed tomography scan revealed gallstones, an elevated
      lesion in the gallbladder, and a cystic liver lesion. Endoscopic retrograde
      cholangiopancreatography demonstrated stenosis of the common bile duct. Cultures
      of the cystic fluid and gallbladder bile were positive for Staphylococcus aureus.
      The patient underwent hepatectomy (inferior S4, S5, and S6), cholecystectomy,
      resection of the common bile duct, and right hemicolectomy. The resected
      specimens revealed gallbladder cancer with the microscopic appearance of a
      papillary adenocarcinoma, and a 12 x 4.5 x 3.5 cm cystic liver lesion with a wall
      7 mm thick. Histologic studies of the wall of the cystic liver lesion revealed
      infiltration by histiocytes and plasma cells, and the presence of fibrous
      connective tissue, which findings are characteristic of inflammatory
      pseudotumors. A 9 x 6 mm elevated lesion, with the microscopic appearance of a
      neuroma, was resected from the common bile duct.

PMID- 7647911
TI  - Gallstones and their composition in patients with ileoanal anastomosis.
AB  - Cholelithiasis is known to occur in 15%-24.5% of proctocolectomized patients.
      However, the clinical features and chemical analysis of gallstones in these
      patients have not been reported. We describe two cases of cholelithiasis that
      developed in patients after proctocolectomy with ileoanal anastomosis. These
      patients had a high output of watery stools and more frequent bowel movements
      than the average for Japanese patients with ileoanal anastomosis. The chemical
      composition of the resected gallstones was 93.0% cholesterol and 80.9%,
      respectively, in the two patients, indicating that cholesterol gallstones are
      formed in patients with ileoanal anastomosis after proctocolectomy.

PMID- 7647914
TI  - Establishment of a human cancer cell line with high potential for peritoneal
      dissemination.

PMID- 7647913
TI  - Kinetics of gastric epithelial cells in duodenal ulcer: local environmental
      factors controlling the proliferation and differentiation of gastric epithelial
      cells.
AB  - The Pathophysiology of peptic ulcer disease is based on heterogenous
      abnormalities of gastric epithelial cell function. Based on clinical
      observations, we proposed the hypothesis that duodenal ulcer can occur with
      normal acid secretion, but that recurrence of duodenal ulcer may be caused by
      genetic and environmental factors that promote altered kinetics in gastric cells;
      i.e., the formation of new cells, the migration of cells, and changes in their
      life span of cells. The factors controlling these processes include feeding, the
      action of endocrine and gut hormones, the action of the autonomic nervous system,
      the microcirculation, and growth factors. In this review, to prove our
      hypothesis, we have summarized the clinical and experimental approaches to reveal
      the environmental factors that control the proliferation and differentiation of
      gastric epithelial cells.

PMID- 7647912
TI  - Pathologic basis of gastric mucosal adaptation to topical injury.

PMID- 7647915
TI  - Phenyl N-tert-butyl nitrone forms nitric oxide as a result of its FE(III)
      catalyzed hydrolysis or hydroxyl radical adduct formation.
AB  - Phenyl N-tert-butyl nitrone (PBN) is commonly employed in spin-trapping studies.
      We report here evidence that PBN in aqueous solutions is decomposed by two
      pathways leading to the generation of nitric oxide (.NO). The first pathway is by
      hydrolysis of PBN, which is strongly catalyzed by ferric iron. The second pathway
      is via PBN-hydroxyl radical adduct formation. .NO was trapped in the presence of
      cysteine and ferrous iron to form a [(cys)2Fe(NO)2]-3 complex, which was measured
      by use of electron paramagnetic resonance (EPR) spectroscopy. A concomitant
      metabolite, benzaldehyde, was detected from both reaction mixtures. We propose
      that PBN is hydrolyzed by Fe3+ or attacked by hydroxyl radical, leading
      eventually to a common transient species, tert-butyl hydronitroxide [t-BuN(O.)H],
      which is further oxidized to a .NO source, t-BuNO. Our data imply that PBN may
      decompose to .NO when used in biological models with oxidative stress conditions.

PMID- 7647916
TI  - Synthesis and evaluation of DMPO-type spin traps.
AB  - The spin traps substituted with some groups at the 4-position of dimethyl-1
      pyrroline N-oxide(DMPO) were compared with DMPO itself regarding their abilities
      as spin traps and their physical properties. 4,5,5-Trimethyl-1-pyrolline N-oxide
      (4MDMPO) and 5,5-dimethyl-4-phenyl-1-pyrolline N-oxide (4PDMPO) were synthesized
      by the Bonnett method, and 5,5-dimethyl-4-hydroxymethyl-1-pyrolline N-oxide
      (4HMDMPO) was made by a unique method from 2(5H)-furanone. The melting points of
      4MDMPO, 4PDMPO and 4HMDMPO were higher than that of DMPO. The magnitude of
      hydrophilicity was in the order of 4HMDMPO, DMPO, 4MDMPO, and 4PDMPO based on the
      partition coefficient experiments in a 1-octanol--water system. Several radicals,
      O2-., HO., .CH3, .CH2OH, .CH(CH3)OH, (CH3)3CO. and H. radicals, were trapped with
      these DMPO derivatives for comparison with the trapping by DMPO itself. Spin
      adducts of O2-. with the three DMPO derivatives showed ESR spectra similar to
      that of DMPO. In spite of the formation of diastereomers arising from spin
      trapping, the line-width enlargement was very small. The intensities and the
      decay rates of the spectra of 4MDMPO-O2-, 4PDMPO-O2-, 4HMDMPO-O2- and DMPO-O2-
      were almost equal. In the trapping of the .OH radical by 4MDMPO, 4PDMPO and
      4HMDMPO, the eight-line ESR spectra observed were different from the well-known
      four-line spectrum of DMPO-OH.

PMID- 7647918
TI  - Spin-trapping and direct EPR investigations on the hepatotoxic and
      hepatocarcinogenic actions of luteoskyrin, an anthraquinoid mycotoxin produced by
      Penicillium islandicum Sopp. Generations of superoxide anion and luteoskyrin
      semiquinone radical in the redox systems consisted of luteoskyrin and liver NADPH
      or NADH-dependent reductases.
AB  - Luteoskyrin is a hepatotoxic and hepatocarcinogenic bisdihydroanthraquinone
      produced by Penicillium islandicum Sopp. By observing the EPR spectra of DMPO
      spin adducts and luteoskyrin semiquinone radical, we investigated in vitro
      whether luteoskyrin is reduced to its semiquinone radical leading to the
      generation of active oxygen species in redox systems catalyzed by NADPH-dependent
      cytochrome reductases of the liver. We found (1) the formation of luteoskyrin
      semiquinone radical in the NADPH-cytochrome P-450 reductase system under
      anaerobic conditions, (2) the generation of O2- in the systems composed of
      luteoskyrin, NAD(P)H, and either rat liver microsomal NADPH-cytochrome P-450
      reductases or submitochondrial particles and (3) dicoumarol showed no effect on
      the O2- generation in the case of submitochondrial particles. From these results
      we proposed that luteoskyrin liver injuries are induced by the active oxygen
      species generated in the process of autoxidation of luteoskyrin semiquinone
      radical which is produced in the one-electron redox systems catalyzed by the
      liver NAD(P)H-dependent cytochrome reductases.

PMID- 7647917
TI  - Detection of free radicals by microdialysis/spin trapping EPR following focal
      cerebral ischemia-reperfusion and a cautionary note on the stability of 5,5
      dimethyl-1-pyrroline N-oxide (DMPO).
AB  - We have examined free radical production in a rat model of focal cerebral
      ischemia using microdialysis coupled with EPR analysis. A microdialysis probe was
      inserted 2 mm into the cerebral cortex, supplied by the right middle cerebral
      artery (MCA), and after a 2-hour washout period with artificial cerebral spinal
      fluid (ACSF), the perfusate solution was changed to ACSF containing the spin
      trapping agent, 5,5-dimethyl-1-pyrroline N-oxide (DMPO). No free radicals were
      detected by DMPO during the pre-ischemia period. Both common carotid arteries and
      the right MCA were then ligated for 90 minutes. Microdialysate collected every 15
      min during the ischemic period demonstrated predominantly superoxide or peroxyl
      radical production. After release of the occlusive sutures, hydroxyl radical
      became apparent initially, then thiyl and carbon centered radicals appeared later
      in samples collected every 15 min for two hours following cortical reperfusion.
      Careful studies on the purification and stability of DMPO solution were performed
      to circumvent artifacts and spurious signals.

PMID- 7647919
TI  - Detection of hydroxyl radical in intact cells of Chlorella vulgaris.
AB  - Using ESR with 5,5-dimethyl-1-pyrroline N-oxide (DMPO) as a spin-trapping
      reagent, we measured the levels of free radical species generated from living
      cells of Chlorella vulgaris var. vulgails (IAM C-534). To investigate the
      production of free radicals in the living Chlorella vulgaris cells, the influence
      of DMPO toward the intact cells of the Chlorella vulgaris using the O2 evolution
      rate was first studied as a guide. Since the O2 evolution rate was not changed by
      DMPO, it was judged that DMPO has no toxicity toward the intact cells of
      Chlorella vulgaris. Only hydroxyl radicals (.OH) were detected as the DMPO-OH
      adduct in the suspension of intact cells of Chlorella vulgaris irradiated with
      visible light. Moreover, since production of .OH was inhibited by some hydroxyl
      radical scavengers such as KI and ethanol, production of .OH was proved to be due
      to hydroxyl radicals. It was also clear that the intensity of .OH increased with
      increasing irradiation intensity of visible light. Therefore, it was suggested
      that .OH might be one of the photoinhibition factors of the intact Chlorella
      vulgaris cells in severe light conditions.

PMID- 7647920
TI  - The role of free radicals in paraquat-induced corneal lesions.
AB  - Paraquat is a synthetic bipyridylium salt widely used as herbicide and defoliant.
      Enzyme-catalyzed redoxcycling of paraquat generates oxygen radicals. The toxic,
      even lethal, effects of paraquat are due to free radical-mediated tissue injury.
      Ocular lesions, sometimes quite severe, have been observed following accidental
      splashing of paraquat solutions onto the eyes. These studies were designed to
      document the generation of paraquat free radicals in corneal tissue, and to
      describe the histological nature of the corneal injuries in experimental animals
      (rabbits and monkeys). The EPR spectrum of rabbit corneas, 30 min. after
      intrastromal injection of paraquat, showed the signal of the free radical of
      paraquat. Ultrastructural studies of corneas 8 days after intrastromal injections
      (100 microliters) of paraquat solutions showed that the initial lesions occur at
      the epithelium/basement membrane interface. In rabbit cornea, dose dependent
      lesions were observed, i.e. whereas 50 mM paraquat caused only minimal damage to
      the epithelial basement membrane, 75 mM caused complete dissolution to the
      basement membrane with some damage to stromal collagen, and loss of epithelium
      with stromal ulceration and severe inflammatory response were observed with 150
      mM paraquat. Monkey corneas were less susceptible than those of rabbits to the
      effects of paraquat. No lesions were observed following intrastromal injections
      of 50 mM or 75 mM paraquat. With higher concentrations of paraquat (100 mM and
      150 mM) the primary injuries were to the proximal and lateral plasma membranes of
      basal epithelial cells; basement membrane alterations were detected only adjacent
      to areas of significant plasma membrane damage. The underlying Bowman's membrane
      and stroma were not affected. Anatomical differences between the corneas of
      rabbit and monkeys as well as possible biochemical differences may account for
      the species differences observed.

PMID- 7647921
TI  - Can spin trapping compounds like PBN protect against self-inflicted damage in
      polymorphonuclear leukocytes?
AB  - Polymorphonuclear leukocytes (PMNs) have been suggested to be damaged by
      superoxide radical generated on their own. The protective capacity of a spin
      trapping compound, phenyl-N-tert-butyl nitrone (PBN) was evaluated for this
      damage which occurs after the induction of superoxide generation. The life span
      of PMNs after superoxide generation was measured in the presence of PBN using the
      cell counting method, and effects of PBN on the amount of superoxide generated
      were quantitated using both cytochrome c reduction and spin trapping with DMPO.
      Results indicated significant extension of life span when PBN was present, and
      the extension was dose dependent. However, the magnitude of life span extension
      was not as large as expected from the decrease of superoxide generation. Possible
      mechanisms for the protection of PMNs by PBN are discussed.

PMID- 7647922
TI  - Pharmacological action of a new spin trapping compound, 2-phenyl DMPO, in the
      adriamycin-induced cardiotoxicity.
AB  - Adriamycin (ADR)-induced cardiotoxicity was adopted in this investigation as a
      reliable model of radical-dependent myocardial pathology allowing both
      quantitative studies of drug activity in the isolated organ and in vivo
      comparison of the cardio-protection vs. general toxicity. Since commercially
      available lipophilic spin trapping compounds were shown to develop significant
      protective activity, in this investigation a newly synthesized spin trap (2
      phenyl-DMPO) was studied. In Langendorff rat heart, 200 microM ADR induced a
      significant impairment of contractile performance, while 2-phenyl-DMPO was not
      cardiotoxic up to the 5 mM concentration. By this dose, 2-phenyl-DMPO induced a
      significant protection against the ADR-induced contractile impairment. In in vivo
      experiments, ADR (9 mg/kg i.v.) produced a significant impairment of ECG,
      coronary flow and contractility. The continuous administration of 2-phenyl-DMPO
      i.p. by osmotic pump delivering 0.3 mumol/hr was unable to protect the animals
      against the cardiotoxic signs. Seven days after ADR administration, severe
      general toxicity (arrest of body weight increase) and myelotoxicity were also
      observed. 2-phenyl-DMPO was unable to protect the animals from these toxic signs.
      The present results confirm that lipophilic spin traps can be a new class of
      antiradical drugs, as confirmed by the experiments performed in the isolated
      heart with the 2-phenyl-DMPO; however, this last compound is probably metabolized
      in vivo to inactivate derivatives.

PMID- 7647923
TI  - Rapid gas chromatographic screening of edible seeds, nuts and beans for non
      protein and protein amino acids.
AB  - Water extraction with subsequent picric acid treatment and solvent washing (ethyl
      acetate and diethyl ether) was employed for the rapid isolation of free amino
      acids from non-aqueous food samples. The isolated amino acids were subjected to
      N(O,S)-isobutyloxycarbonylation followed by solid-phase extraction and tert.
      butyldimethylsilylation for direct analysis by gas chromatography and gas
      chromatography-mass spectrometry. When the present method was applied to nineteen
      food samples (common beans, seeds, and nuts), seventeen protein amino acids and
      fifteen non-protein amino acids were simultaneously screened. Eleven non-protein
      amino acids including gamma-aminobutyric acid, pipecolic acid, pyroglutamic acid,
      alpha-aminobutyric acid, alpha-aminoadipic acid, and beta-alanine were
      tentatively identified, and four compounds assumed to be non-protein amino acids
      remained unidentified.

PMID- 7647925
TI  - Evaluation of solid-phase extraction procedures in peptide analysis.
AB  - Solid-phase extraction (SPE) procedures for peptide isolation and fractionation,
      based on non-polar and ionic interactions, were evaluated using small synthetic
      peptides and casein enzymatic hydrolysates. SPE based on hydrophobic phases is a
      useful, efficient and rapid procedure for peptide extraction and concentration.
      It allows a successful peptide fractionation using eluents that contain an
      increasing content of acetonitrile in the presence of trifluoroacetic acid.
      Differences regarding selectivity are observed between sorbents. Non-polar
      interaction with C18 sorbents is adequate for the isolation of very polar and
      hydrophobic peptides. CN sorbents are only adequate for very hydrophobic
      peptides. PH, CH, C8 and C2 sorbents are useful for isolating and fractionating
      hydrophobic and very non-polar peptides, but generally not for very polar
      peptides. Ionic solid-phase extraction using Accell Plus cartridges of QMA
      (quaternary methylammonium) and CM (carboxymethyl) are very useful for the
      fractionation of peptide mixtures into basic, acidic and neutral pools of
      peptides. It can be concluded that SPE using these procedures is a useful tool
      for the isolation and fractionation of peptides from biological and food samples.

PMID- 7647924
TI  - Molecularly imprinted polymers on silica: selective supports for high-performance
      ligand-exchange chromatography.
AB  - Thin coatings of molecularly imprinted, metal-complexing polymers have been
      grafted to activated silica beads suitable for high-performance liquid
      chromatography (HPLC). Propylmethacrylate-activated silica particles were coated
      by copolymerization with a metal-chelating monomer, Cu(2+)-[N-(4-vinylbenzyl)
      imino]diacetic acid, a metal-coordinating (imidazole) template, and ethylene
      glycol dimethacrylate. After extraction to remove the template and re-loading
      with metal, the composite materials re-bind the templates with which they were
      prepared and exhibit selectivities comparable to bulk-polymerized imprinted
      materials. The strong Cu(2+)-imidazole interaction, desirable for creating a high
      fidelity imprint, leads to excessive retention in elution chromatography. By
      replacing the copper in the imprinted metal-complexing polymers with weaker
      binding Zn2+, these novel ligand-exchange supports can effect partial to complete
      chromatographic separation of their bis-imidazole templates from other, highly
      similar imidazole-containing substrates. This "bait-and-switch" approach can
      significantly enhance the performance of molecularly imprinted materials.
      Scatchard plots of equilibrium binding data show a significant degree of
      heterogeneity in the imprinted binding sites of material prepared with a bis
      imidazole template, but not with a mono-imidazole template. The best
      chromatographic separations are observed with small sample sizes, where the
      substrates occupy the strongest (highest-fidelity) sites.

PMID- 7647926
TI  - Heterogeneity of the bovine kappa-casein caseinomacropeptide, resolved by liquid
      chromatography on-line with electrospray ionization mass spectrometry.
AB  - Microheterogeneity occurs in the population of caseinomacropeptides (residues 106
      169 of kappa-casein) due to variation in the extent and type of oligosaccharide
      linked to this phosphoglycopeptide. Although caseinomacropeptide A variant (CMPA)
      was poorly resolved using reversed-phase high-performance liquid chromatography
      (RP-HPLC) with spectrophotometric detection, it could be analysed with on-line
      electrospray-ionization mass spectrometry (ESI-MS). From the already established
      O-linked glycan chains at least fourteen glycosylated forms of CMPA were
      identified, besides the non-glycosylated and multiphosphorylated (1, 2 or 3
      phosphate groups) peptides, giving a maximum number of eighteen known forms.
      Major subcomponents in CMPA are disialylated species. A maximum of three out of
      the five potential glycosylation sites were found to be substituted with
      carbohydrate chains in the most highly glycosylated forms, which may contain up
      to six N-acetylneuraminic acid residues per molecule. A minor form,
      diphosphorylated with one disialylated chain, was also detected. From these
      results, it was shown that the on-line coupling of HPLC with ESI-MS offers a very
      promising alternative for the analysis of complex mixtures.

PMID- 7647927
TI  - Diode laser-induced fluorescence detection in capillary electrophoresis after pre
      column derivatization of amino acids and small peptides.
AB  - The use of diode laser-induced fluorescence (DIO-LIF) detection in the field of
      capillary electrophoresis (CE) is examined. A simple but sensitive detection
      system was constructed. The performance of the system was evaluated with respect
      to design factors and its sensitivity was compared with the theoretically
      achievable sensitivity. To enhance the applicability of direct DIO-LIF detection
      in CE, a derivatization method for amines was developed. A red-absorbing label,
      consisting of a dicarbocyanine fluorophore with a succinimidyl ester
      functionality, was synthesized for this purpose. After derivatization of 1 x 10(
      6) M glycine, a detection limit of 0.1 amol was observed for the labeled glycine.
      Similar detection limits were observed for other amino acids. To show that
      derivatization preserves the separation efficiency of CE for the analytes
      examined, 18 amino acids and tyramine were separated with micellar electrokinetic
      chromatography after labeling. In addition, even labeled peptides, including
      structurally related enkephalin-type compounds, were separated from each other
      with zone electrophoresis. To test the applicability of the derivatization method
      to biological samples, tyramine was determined in urine before and after the
      consumption of cheese.

PMID- 7647928
TI  - Loss of basement membranes in the invading front of O-1N, hamster squamous cell
      carcinoma with high potential of lymph node metastasis: an immunohistochemical
      study for laminin and type IV collagen.
AB  - The change in immunohistochemical localization of the two basement membrane
      molecules, laminin and type IV collagen, was studied in relation to tumor growth
      and lymphatic invasion in the transplanted hamster squamous cell carcinoma, O-1N,
      that has a high potential of lymph node metastasis. At 1 week after
      transplantation, the tumors consisted of large round-shaped nests of
      approximately 200 mm in diameter, 80% of which were encircled by continuous
      laminin and type IV collagen positive lines representing the basement membrane.
      At 5 weeks, however, the tumor cell nests became half in diameter with invasion
      in small islands or cords at the periphery and only 40% of them had continuous
      basement membrane. At 10 weeks, the basement membranes were disrupted in varying
      degrees in approximately 90% of the tumor cell nests. The disruption was most
      conspicuous on the outer and invading side of the nests. Lymphatic invasion and
      lymph node metastasis were observed in animals after 5 weeks of transplantation
      and the immunoreactivity was absent around tumor cell clusters growing in
      lymphatic spaces. The findings indicate that the disappearance of basement
      membrane and reduction in size of tumor cell nests are essential signs for local
      invasion of tumor cells leading to lymphatic invasion and metastasis to regional
      lymph nodes.

PMID- 7647929
TI  - Incidence and distribution of isolated atrial amyloid: histologic and
      immunohistochemical studies of 100 aging hearts.
AB  - The incidence and anatomic distribution of isolated atrial amyloid (IAA) in 100
      aging hearts were studied histologically and immunohistochemically using
      antibodies against alpha-human-atrial natriuretic peptide (alpha-ANP), human
      transthyretin (TTR) and human amyloid P component (AP). Ninety-one of 100 hearts
      (91%) had amyloid deposits in the atria. Amyloid deposits in all 91 hearts
      reacted with alpha-ANP and AP antisera, and in four hearts other amyloid deposits
      that reacted with TTR antiserum were coincidentally seen in the atria. The
      prevalence of IAA deposition, using a semiquantitative evaluation, was
      significantly higher in the hearts from patients over 80 years of age, from
      women, those weighing over 450 g, with a thickened left ventricular wall (> 1.4
      cm) and with multiple myocardial scars. IAA deposition showed a significant
      distribution in the auricle and left atrium; it was located mostly in the
      interstitium of the subendocardial layer and the subendocardial myocardium. These
      results indicate that IAA occurs more frequently than previously appreciated in
      the elderly and in patients with certain cardiac disorders.

PMID- 7647930
TI  - Immunohistochemical localization of glutathione peroxidase, a lipid peroxidase
      scavenger, in atherosclerotic lesions of human arteries.
AB  - The localization of glutathione peroxidase (GSH-PO) in the human arteriosclerotic
      lesions was investigated by immunohistochemical methods. GSH-PO is an enzyme that
      effectively reduces lipid peroxides. It is also known that its synthesis is
      significantly increased by lipid peroxides, the substrate of the enzyme.
      Accordingly, the increased expression of GSH-PO would indicate the promotion of
      lipid peroxidation in the site. Immunohistochemistry for Apo-B protein, the major
      protein component of plasma low density lipoprotein (LDL), was also performed to
      show the amount of plasma LDL permeation and deposition on the arterial wall.
      Atheromatous plaques contained numerous GSH-PO positive cells with foamy
      cytoplasm, while normal arterial walls were almost devoid of GSH-PO positive
      cells. Immunoelectron microscopically, the GSH-PO reaction products were observed
      diffusely in the cytoplasm of these cells. The deposition of Apo-B was closely
      related to the localization of GSH-PO positive cells in the atheromatous lesions.
      These findings suggest that the lipid peroxidation that surpasses the protective
      actions of GSH-PO may cause foamy change of smooth muscle cells and macrophages
      to ultimately form atherosclerotic lesions.

PMID- 7647931
TI  - Growth patterns and interstitial invasion of small hepatocellular carcinoma.
AB  - Twenty-five cases of small hepatocellular carcinoma (HCC; diameter < or = 30 mm)
      were evaluated for overall morphologic features and growth patterns. The tumors
      often showed a well-differentiated, normotrabecular histologic pattern and
      insidious interstitial invasion, which resembled benign hepatocytes scattered in
      connective tissues. As the tumor grew, a less-differentiated tumor area became
      predominant. Portal tracts included in small HCC nodules were quantitatively
      assessed, revealing that they progressively reduced in number with tumor growth.
      The tumor margin was often reported to be unclear. The present results indicate
      that the histologic grade of tumor differentiation, capsular formation, existence
      of liver cirrhosis and patterns of interstitial invasion are important factors
      for determining the nature of the margin. The score of argyrophilic nuclear
      organizer regions (AgNOR) was examined in 5 cases showing typical interstitial
      invasion with the insidious type. In each case, the AgNOR score of the invading
      tumor cells was lower than that of tumor cells within the HCC nodules, but higher
      than benign hepatocytes in cirrhotic parenchyma. It clarified that the growth
      activity of well-differentiated HCC was rather suppressed upon their interstitial
      invasion.

PMID- 7647932
TI  - The proliferating cell nuclear antigen (PCNA) index correlates with the grade of
      cytologic atypia in well-differentiated early adenocarcinomas of the large
      intestine.
AB  - Well-differentiated colorectal adenocarcinomas are subclassified into carcinoma
      with high-grade atypia (CAH) and carcinoma with low-grade atypia (CAL) based on
      their cellular atypia. It is proposed that CAH and CAL are different in
      histologic prognostic factors and that the former should be regarded as carcinoma
      with high-grade malignancy and the latter as low-grade malignancy. In this study,
      the differences in cell-proliferative activity between CAH and CAL were examined
      using a monoclonal antibody to the proliferating cell nuclear antigen (PCNA). The
      PCNA index and mitotic index of 27 early colorectal carcinomas (9 CAL, 5 CAH, and
      13 carcinomas with mixed low- and high-grade atypia) was evaluated in relation to
      their depth of invasion. In intramucosal lesions, both indices were higher in CAH
      (78%, 0.89%) than in CAL (68%, 0.47%; P < 0.01). In lesions invading into the
      submucosa, the PCNA and mitotic indices were also higher in CAH (75%, 0.65%) than
      in CAL (35%, 0.19%; P < 0.01). A significant correlation was observed between the
      PCNA index and the mitotic index in the mucosal lesions (P < 0.05). These results
      indicate that CAH has a higher proliferative activity than CAL, and support the
      current authors' proposal that CAH is a high-grade malignancy and CAL low-grade
      malignancy.

PMID- 7647933
TI  - Contribution of Epstein-Barr virus to development of malignant lymphoma of the
      thyroid.
AB  - Epstein-Barr virus (EBV)-related mRNA, their products and apoptosis were
      investigated in 32 cases of malignant lymphoma of the thyroid (MLT) and 30 cases
      of Hashimoto's thyroiditis (HT) by in situ hybridization, immunohistochemistry
      and nick end labeling method on routinely processed tissue sections. In MLT, EBV
      encoded small RNA (EBER) were detected in three cases, consisting of a
      follicular, predominantly large cell type (FL), a diffuse, large cell type (DL)
      and a large cell, immunoblastic type (IBL). In EBER-positive cases, IBL that was
      positive for T cell marker, exhibited neither BamHl H Left Frame 1 (BHLF1)
      transcript, EBV-encoded latent membrane protein (LMP) nor BamHl Z Left Frame 1
      (BZLF1) gene product (ZEBRA), whereas both BHLF1 and ZEBRA were found in a small
      portion of the tumor cells in the FL and DL that expressed B cell marker and LMP.
      Apoptotic cells were observed in only a few lymphocytes in HT, and in a few non
      neoplastic lymphocytes and various numbers of lymphoma cells in MLT. The
      apoptotic cell ratio of MLT tended to be higher in lower grade lymphomas. These
      results suggest that EBV may participate in the malignant transformation from HT
      to MLT.

PMID- 7647934
TI  - Immunoglobulin idiotypic specificity of AIDS-associated lymphomas and their
      experimental model.
AB  - B cell non-Hodgkin's lymphoma (B-NHL) occurring in immunocompromised hosts, such
      as acquired immune deficiency syndrome (AIDS) patients, is a high-grade
      malignancy resistant to regular chemotherapy. To determine whether immunotherapy
      with public anti-Ig idiotype antibodies can be used to treat these NHL, the Ig
      idiotype specificity of six NHL in AIDS patients (AIDS-ML) and 23 B-NHL
      experimentally induced in immunocompromised mice (SCID mice) was investigated.
      One of the six AIDS-ML and two of the 23 experimental B-NHL reacted monoclonally
      with a single public antibody, while one AIDS-ML and three experimental B-NHL
      reacted polyclonally with two or three different antibodies. The presence of Ig
      idiotypic polyclonality requires special consideration with regard to the
      introduction of anti-Ig idiotype immunotherapy in these cases.

PMID- 7647935
TI  - Circumferential Peyronie's disease involving both the corpora cavernosa.
AB  - An extraordinary form of Peyronies disease is reported. The patient was a 52 year
      old male, who died of a malignant thymoma with multiple bone metastasis,
      extensive pleural carcinomatosis of the left lung and some metastatic nodules in
      the liver and the mesenterium. At autopsy, the proximal and middle portions of
      the penis were very hard. Macroscopically, the entire tunica albuginea of both
      the corpora cavernosa was markedly thickened, 2-4 mm; and calcified.
      Microscopically, the tunica albuginea showed extensive hyaline degeneration,
      calcification and ossifying foci with osteoblasts and osteoclasts. Inflammatory
      cells were frequently found beneath the thickened tunica albuginea. In the corpus
      cavernosum, cavernous arteries showed marked intimal thickening and medial
      muscular degeneration with a few inflammatory cells. Smooth muscles of the stroma
      were extensively atrophic and degenerative, and some of them were infiltrated
      with a few inflammatory cells. In the corpus spongiosum, the tunica albuginea was
      not thickened, but the smooth muscle in the stroma was atrophic and degenerative
      and a few inflammatory cells were also found. Surprisingly, there was no Littres
      gland around the urethra. In Peyronies disease, the dorsal part of the penis is
      usually involved, and less frequently lateral or ventral sites are involved. The
      circumferential involvement of both the corpora cavernosa has not been reported
      until now, as far as the authors know.

PMID- 7647936
TI  - Peutz-Jeghers syndrome with osseous metaplasia of the intestinal polyps.
AB  - A case of Peutz-Jeghers syndrome (PJS) with osseous metaplasia in three of 15
      hamartomatous polyps of the small intestine is reported. At 35 years of age, the
      patient was diagnosed as having PJS by cutaneous pigmentation around the mouth
      and polyposis of the stomach, duodenum and intestine. Fifty-two polys of the
      large intestine were resected, which were characteristic of those of PJS. Three
      of them showed adenomatous and carcinomatous changes, but there was no osseous
      metaplasia in any of the resected polyps. At age 40, he had surgery under the
      diagnosis of intestinal obstruction. There were 15 polyps in the resected
      jejunum. These polyps were also characteristic of those of PJS. Additionally,
      three of these polyps were accompanied by osseous metaplasia. Histologically,
      mature bone formation and calcification were found close to the hyperplastic
      glands in the submucosa or in the propriate muscle. Malignant transformation was
      not observed. Osseous metaplasia is extremely rare in benign polyps, and it has
      not been reported in hamartomatous polyps of PJS to date. The knowledge of this
      association may be helpful in the clinical diagnosis of this benign lesion in
      PJS.

PMID- 7647937
TI  - Nasal glioma: an immunohistochemical and ultrastructural study.
AB  - A case of a 14 month old Japanese female infant presenting with nasal glioma is
      reported. The tumor had been noticed at the nasal radix since birth and had
      slowly and progressively enlarged. There was no communication between the tumor
      and the cranial cavity on radiological examination. The tumor was macroscopically
      anchored to the nasal septum by a fibrous stalk, and histologically consisted of
      nests or trabeculae of either polygonal or spindle cells with plump eosinophilic
      cytoplasm and oval nuclei, separated by vascular-rich connective tissue
      intermingled with multinucleated giant cells. These tumor cells were
      immunohistochemically positive for glial fibrillary acidic protein as well as for
      S-100 protein and vimentin. An electron microscopic examination revealed collagen
      fibers and basal lamina between the tumor cells and the fibroblasts. Tumor cells
      possessed abundant intermediate filaments, which showed occasional Rosenthal
      fiber-like structures, in their cytoplasm and processes. A few oligodendrocytes
      and cilia of 9 microtubule doublets either with or without 2 central microtubules
      were also noted. These clinicopathological findings suggested that this tumor was
      once an encephalo(meningo)cele, which probably degenerated as a result of the
      loss of intracranial communication and then appeared to be isolated from the
      intracranial tissue.

PMID- 7647938
TI  - Hyalinizing trabecular adenoma of the thyroid: its unusual cytoplasmic
      immunopositivity for MIB1.
AB  - The monoclonal antibody Ki-67 reacts with a human nuclear cell proliferation
      associated antigen that is expressed in all active parts of the cell cycle and is
      well established as a marker of cell proliferation. However, the Ki-67 method
      requires fresh frozen material. Recently, MIB1 has been reported to give an
      immunohistochemical staining pattern identical to Ki-67 on paraffin-embedded
      tissue sections, frozen sections and cytological samples. This proliferation
      associated antigen is apparently localized in the nucleus. Recently, we performed
      immunohistochemical staining using the monoclonal MIB1 antibody upon a variety of
      tumors and non-neoplastic conditions of the thyroid. Tumor cells of hyalinizing
      trabecular adenoma revealed an intense cytoplasmic immunopositivity for MIB1. In
      contrast, cytoplasmic immunostaining for MIB1 was negative in all other thyroid
      tumors and non-neoplastic lesions. Because of this unusual staining pattern, we
      repeated the staining of all cases and found the results to be reproducible.
      Therefore, we believe that positive cytoplasmic immunostaining for MIB1 is a
      characteristic finding of hyalinizing trabecular adenoma and is useful in
      differentiating it from other thyroid tumors.

PMID- 7647939
TI  - Safe discontinuation of antihypertensive therapy.

PMID- 7647940
TI  - Requiem for traditional medical practice in the United States.

PMID- 7647941
TI  - Tracking the changes in physician practice settings.
AB  - OBJECTIVE: To describe the relationships among types of practice settings and
      physician characteristics and to document changes in these relationships over
      time. DESIGN: Two national telephone surveys of randomly selected young
      physicians were conducted in 1987 and 1991. The 1991 survey included reinterviews
      of 1987 respondents, providing both cohort and repeated cross-sectional data.
      PARTICIPANTS: The 1987 survey included data on 5312 physicians who had between 2
      and 6 years of practice experience and were under age 41 years. The 1991 survey
      included data on 5002 physicians under age 45 years and in practice between 2 and
      10 years, including 2151 reinterviews of 1987 respondents. MAIN OUTCOME MEASURES:
      Practice settings were classified as traditional, government, group, or managed,
      based on ownership, practice type, group size, and managed care contracts.
      RESULTS: Physician sex, race/ethnicity, specialty, and type of medical school
      were related to the type of practice setting. Young physicians were less likely
      to practice in traditional settings in 1991 than in 1987 and were more likely to
      practice in organized practice settings, especially in managed practices.
      CONCLUSION: Between 1987 and 1991, there was a significant shift away from
      traditional physician practice settings toward organized practice settings.

PMID- 7647942
TI  - An individualized educational model for the remediation of physicians.
AB  - OBJECTIVE: To design and implement an individualized program of evaluation and
      education to provide remedial experiences to physicians. DESIGN AND SETTING: An
      evaluation and educational program for physicians practicing in New York State.
      PARTICIPANTS: Physicians referred for evaluation and possible remedial
      educational experiences from the New York State Office of Professional Medical
      Conduct, from the New York State Committee on Physicians' Health, or self
      referred. MAIN OUTCOME MEASURES: Educational programs designed to meet the
      individually identified educational needs of physicians and placement of
      physicians in educational settings that facilitate their meeting the program
      goals and issues raised by the Office of Professional Medical Conduct. RESULTS:
      Of the 28 physicians who have undergone evaluation activities, at the time of
      this report, five (18%) had completed their educational programs, five (18%) were
      participating in directed educational programs, five (18%) had approved
      educational programs and were awaiting placement, and 10 (36%) were awaiting
      acceptance of their program by the Office of Professional Medical Conduct.
      CONCLUSIONS: A comprehensive evaluation program can identify areas amenable to
      education and target individualized remedial educational experiences that may
      enable physicians to become contributing members of the medical community.

PMID- 7647943
TI  - Combined methotrexate and misoprostol for early induced abortion.
AB  - OBJECTIVE: To determine the effectiveness and side effects of and subject
      satisfaction with an induced abortion by administration of methotrexate and
      intravaginal misoprostol. SUBJECTS AND DESIGN: Prospective trial of 100
      consecutive pregnant women aged 18 years or older at 8 weeks' gestation or less
      and wanting an abortion. INTERVENTIONS: Intramuscular administration of 50 mg of
      methotrexate per square meter of body surface area on day 1 and a misoprostol 800
      micrograms vaginal suppository on day 3. Administration of misoprostol was
      repeated the following day if no bleeding occurred after the first dose.
      PROTOCOL: After pregnancy dating by clinical criteria, subjects were followed up
      with serum beta-human chorionic gonadotropin (beta-hCG) determinations on days 1,
      7, and 14 and a high-sensitivity urine hCG test every 2 weeks until the value was
      less than 10 IU/L. Subjects completed a daily symptom log and satisfaction
      questionnaire on day 14. MAIN OUTCOME MEASURES: Complete abortion as defined by
      vaginal bleeding and a beta-hCG value of less than 10 IU/L without surgical
      intervention, complications and side effects, and patient satisfaction. RESULTS:
      Ninety-seven subjects had a complete abortion and one subject had vaginal
      bleeding and a 94% decrease of her beta-hCG value on day 7 but was subsequently
      unavailable for follow-up. Two subjects required surgical procedures: one with a
      continued pregnancy and one for excessive bleeding. No failures or complications
      occurred in early gestations prior to 45 days from the last menstrual period.
      Seventy-three percent responded to misoprostol treatment with bleeding within 12
      hours and had a mean decrease of 90% in their beta-hCG value on day 7. Twenty
      seven percent had no immediate bleeding response to misoprostol administration,
      began bleeding on day 10 (SD, 8 days), and had a mean decrease of 10% in their
      beta-hCG value on day 7. Seventy percent reported nausea; 46%, diarrhea; and 23%,
      vomiting. Ninety-three percent agreed that the procedure was acceptable and 95%
      would recommend the procedure. CONCLUSIONS: Methotrexate and misoprostol were
      effective in inducing an abortion up to 8 weeks. Home administration of a
      compounded misoprostol vaginal suppository was successful. Although
      gastrointestinal tract side effects were common, women found the procedure and
      its side effects acceptable.

PMID- 7647944
TI  - Knowledge and experience with Alzheimer's disease. Relationship to resuscitation
      preference.
AB  - BACKGROUND: Previous studies suggest that 20% to 67% of patients would desire
      cardiopulmonary resuscitation (CPR) even if they had advanced Alzheimer's
      disease. These preferences were not affected by education about CPR. We
      hypothesized that CPR preferences in scenarios involving Alzheimer's disease are
      influenced more by knowledge of or experience with Alzheimer's disease than by
      knowledge of CPR and its outcomes. METHODS: We performed a random digit-dialing
      telephone survey of adult Kentuckians in June 1993. A total of 661 persons
      responded. We asked respondents whether they have had a friend or family member
      with Alzheimer's disease and whether they had cared for that person at home. We
      then assessed basic knowledge of Alzheimer's disease and CPR. We read to one half
      of respondents an educational paragraph describing CPR and its outcomes. Finally,
      we asked respondents their CPR preference if they were to develop Alzheimer's
      disease. RESULTS: Overall, 22% of respondents would probably or definitely want
      CPR if they had Alzheimer's disease. With the use of simultaneous multiple linear
      regression, predictors of refusing CPR in scenarios involving Alzheimer's disease
      included knowledge of or experience with Alzheimer's disease (P < .001), older
      age (P < .001), greater income (P < .004), female sex (P < .01), and nonwhite
      race (P < .04). Baseline knowledge of CPR did not affect CPR preferences, nor did
      being read the educational paragraph. CONCLUSIONS: Cardiopulmonary resuscitation
      preferences in scenarios involving Alzheimer's disease are strongly associated
      with knowledge of or experience with Alzheimer's disease more so than with
      knowledge of CPR. These findings suggest that in eliciting patients' CPR
      preferences in an advanced directive, care must be taken that patients understand
      the condition presented in the scenario (eg, Alzheimer's disease).

PMID- 7647945
TI  - Risk factors for the development of bacteremia in nursing home patients.
AB  - BACKGROUND: While bacteremia has been studied in hospitalized elderly, there have
      been few studies in nursing home patients. We hypothesized that the presence of
      functional impairment would be associated with the development of bacteremia.
      OBJECTIVE: To determine risk factors for bacteremia in nursing home patients.
      DESIGN: Case-control study. Admission characteristics of cases and controls were
      compared. For cases, characteristics of the illness, mortality rates, origin of
      bacteremia, and organisms were recorded. SETTING: A 320-bed long-term care
      hospital and nursing home. SUBJECTS: Cases were patients with at least one blood
      culture positive for pathogenic organisms. The next patient admitted after the
      admission date of a case entered the control group. MAIN OUTCOME MEASURE:
      Admission characteristics of patients associated with the development of
      bacteremia. Clinical characteristics of cases and admitting characteristics
      associated with death caused by bacteremia were also determined. RESULTS: Twenty
      six cases were identified, for an incidence of 0.24 per 1000 patient-days. There
      were significant associations between the development of bacteremia and the
      presence of a urinary catheter (P = .002 by chi 2 analysis) or urinary
      incontinence (P = .01 by chi 2 analysis). Men (P = .09) and patients with
      tracheostomies (P = .08 by chi 2 analysis) were somewhat more likely to develop
      bacteremia, but these associations were not statistically significant. The only
      admission characteristic of cases that was associated with death caused by
      bacteremia was hypocholesterolemia (3.79 mmol/L [147 mg/dL] in patients who died
      vs 5.05 mmol/L [195 mg/dL] in patients who survived, P = .03 by t test).
      CONCLUSIONS: Nursing home patients with urinary incontinence or a urinary
      catheter are at increased risk of bacteremia.

PMID- 7647946
TI  - Somatization. Diagnosis and management.
AB  - Somatization, the somatic expression of psychological distress, occurs in a large
      proportion of primary care patients. It is associated with substantial distress
      and impairment and with increased health care utilization. Some somatizing
      patients have a history of multiple unexplained complaints (somatization
      disorder), others are excessively worried about serious illness
      (hypochondriasis), and still others have psychiatric disorders that present with
      somatic symptoms (depression and anxiety). In general, somatizing patients are
      characterized by abnormal illness behavior (eg, failure to respond to treatment,
      excessive utilization of care) and psychological distress (eg, depressive
      symptoms, psychosocial stressors). Recognition requires alertness to
      characteristic features and skillful interview technique. Successful management
      begins by legitimizing symptoms. Restraint should be used in performing workups
      and assigning diagnoses to somatizing patients. Treatment goals should be
      clarified and regular visits scheduled. Also, behaviors that threaten the
      physician-patient relationship should be dealt with. Depression and anxiety
      should be treated when present. Pharmacologic and psychological treatments for
      somatizing patients have been described, although none has proven efficacy.

PMID- 7647947
TI  - A telemedicine primer. An introduction to the technology and an overview of the
      literature.
AB  - The examination of patients by telemedicine is currently experiencing a
      resurgence of interest, perhaps spurred by the increase in activity in managed
      care and major technologic advances. The history and recent publications show
      rapid change in the areas of interactive video and store-and-forward equipment,
      available communications media, and medical peripherals. Several existing
      demonstration projects serve as practical examples of the potential of
      telemedicine systems. Important research and clinical care issues and
      opportunities for constituency building await participation by primary care
      physicians.

PMID- 7647948
TI  - Conversion disorder presenting as gait disturbance in an adolescent.
AB  - Conversion disorder is a psychiatric diagnosis in which the loss of function on
      presentation mimics organic disease. Although rare, it is most common in
      adolescents and young adults. This report describes an adolescent with conversion
      disorder who presented with progressive bilateral lower-extremity weakness and
      impaired gait. As with all patients with conversion disorder, prompt diagnosis
      without extensive testing was essential to initiating appropriate therapy in this
      patient.

PMID- 7647949
TI  - Impact of the local atrial electrogram in AV nodal reentrant tachycardia:
      ablation versus modification of the slow pathway.
AB  - INTRODUCTION: The purpose of this study was to determine the predictors of
      successful ablation versus modification sites of the slow pathway in patients
      with AV nodal reentrant tachycardia. Complete elimination of slow pathway
      conduction ("ablation") is considered to be an appropriate endpoint during
      radiofrequency (RF) current delivery, whereas the persistence of residual slow
      pathway conduction with or without single echo beats ("modification") may be
      indicative of tachycardia recurrence. METHODS AND RESULTS: Of 131 patients, 71
      consecutive patients were followed for 15.1 +/- 7.6 months. After elimination of
      inducible AV nodal reentrant tachycardia in all patients, residual slow pathway
      conduction (modification) persisted in 38 patients, whereas complete elimination
      of slow pathway conduction (ablation) was documented in 33 patients. Including
      electrophysiologic study after 5 to 7 days and after 3 to 6 months, 6 (8.4%)
      patients had recurrences: 5 with residual slow pathway conduction after the
      procedure and 1 with complete elimination of slow pathway conduction (P < 0.05).
      As compared with modulated sites, ablation sites of the slow pathway were
      characterized as follows: (1) duration of the local atrial electrogram (AEGM)
      (66.7 +/- 10.2 vs 54.1 +/- 12.6 msec, P < 0.01); (2) interval from the end of the
      AEGM to onset of His-bundle deflection (4.4 +/- 8.2 vs 16.1 +/- 9.3 msec, P <
      0.01); and (3) number of peaks of the AEGM as an indicator of fractionation (4.1
      +/- 0.7 vs 3.0 +/- 0.8, P < 0.01). The rate of junctional tachycardias (103.4 +/-
      12.1 vs 102.1 +/- 16.9 per min), the AV ratio (0.4 +/- 0.5 vs 0.5 +/- 0.5), the
      number of RF current deliveries (4.1 +/- 4.4 vs 4.5 +/- 4.4), the duration of the
      procedure (124.1 +/- 45.3 vs 125.6 +/- 42.3 min), and the fluoroscopy time (15.5
      +/- 10.8 vs 16.6 +/- 9.6 min) as well as power and total energy of RF current
      deliveries and the anatomically calculated catheter position at the successful
      site were not statistically different. A subset analysis in patients who received
      only a single RF application showed the same results for both groups. Patients
      without recurrence (n = 65) were found to have longer duration of the AEGM (61.9
      +/- 14.6 msec) and a shorter interval from the end of AEGM to the onset of His
      bundle deflection (10.1 +/- 12.2 msec) than patients with recurrence (n = 6)
      (47.5 +/- 7.5 msec and 20.8 +/- 12.8 msec, respectively). CONCLUSION: Complete
      ablation of the slow pathway resulted in a lower recurrence rate. The complete
      ablation approach is feasible using precisely analyzed local AEGMs to guide RF
      current in AV nodal reentrant tachycardia in a short procedure time.

PMID- 7647950
TI  - Responses of the transmembrane potential of myocardial cells during a shock.
AB  - INTRODUCTION: The purpose of this investigation was to study the transmembrane
      potential changes (delta Vm) during extracellular electrical field stimulation.
      METHODS AND RESULTS: Vm was recorded in seven guinea pig papillary muscles in a
      tissue bath by a double-barrel microelectrode with one barrel in and the other
      just outside a cell while shocks were given across the bath. The short distance
      (15 to 30 microns) between the two microelectrode tips and alignment of the tips
      parallel to the shock electrodes eliminated the shock artifact. Following ten S1
      stimuli, an S2 shock field created by a 10-msec square wave was delivered during
      the action potential plateau or during diastole through shock electrodes 1 cm on
      either side of the tissue. Four shock strengths creating field strengths of 1.7
      +/- 0.1, 2.9 +/- 0.2, 6.1 +/- 0.6, and 8.8 +/- 0.9 V/cm were given for the same
      impalement. Both shock polarities were given at each shock strength. For shocks
      delivered during the action potential plateau, the magnitudes of the peak delta
      Vm caused by the above four potential gradients were 21.1 +/- 8.2, 33.6 +/- 13.6,
      49.9 +/- 24.2, and 52.3 +/- 28.0 mV (P < 0.05 among the four groups) for the
      shocks causing depolarization and 37.9 +/- 14.2, 56.6 +/- 16.4, 83.1 +/- 19.4,
      and 92.9 +/- 29.1 mV (P < 0.05 among the four groups) for the shocks causing
      hyperpolarization. Though delta Vm increased as potential gradients increased,
      the relationship was not linear. The magnitude of hyperpolarization was 1.9 +/-
      0.5 times that of depolarization when the shock polarity was reversed (P < 0.05).
      As potential gradients increased from 1.7 +/- 0.1 to 8.8 +/- 0.9 V/cm, the time
      constant of the membrane response decreased significantly from 3.5 +/- 1.8 to 1.6
      +/- 0.7 msec for depolarizing shocks and from 6.0 +/- 3.1 to 3.4 +/- 1.9 msec for
      hyperpolarizing shocks (P < 0.01 vs depolarizing shocks). For shocks delivered
      during diastole, hyperpolarizing shocks induced triphasic changes in Vm during
      the shock, i.e., initial hyperpolarization, than depolarization, followed again
      by hyperpolarization. CONCLUSION: During the action potential plateau, the
      membrane response cannot be represented by a classic passive RC membrane model.
      During diastole, activation upstrokes occur even during hyperpolarization caused
      by shocks creating potential gradients between approximately 2 and 9 V/cm.

PMID- 7647951
TI  - Homing in on the coupling between defibrillation shocks and the cardiac membrane
      potential.

PMID- 7647952
TI  - Temperature measurement as a determinant of tissue heating during radiofrequency
      catheter ablation: an examination of electrode thermistor positioning for
      measurement accuracy.
AB  - INTRODUCTION: Temperature monitoring has been proposed as a control for lesion
      occurrence and dimension during radiofrequency transcatheter ablation. Effective
      temperature measurement depends on thermistor positioning relative to the heated
      cardiac tissue and the convective cooling effects of the circulation. But the
      accuracy of a single tip thermistor as a measure of peak electrode-tissue
      interface temperature is unknown. METHODS AND RESULTS: A standard 8-French, 4-mm
      electrode catheter with 5 thermistors (1 tip thermistor, 4 radial thermistors)
      was used to deliver radiofrequency energy in vitro to 3 porcine right ventricles
      and in vivo to 7 mongrel dogs. In vitro, the catheter orientation was varied. In
      vivo the catheter was positioned under fluoroscopy at a variety of atrial,
      tricuspid annular, and ventricular sites, with no attempt to adjust catheter
      orientation. In both cases varied discrete power levels were used so that a wide
      temperature range was attained. Lesions created in vivo with a standard, single
      thermistor tipped electrode were compared to those of a catheter with a
      thermistor extending 1 mm from the tip. Power was varied and tip thermistor
      temperatures recorded. All lesions were examined pathologically. Comparisons of
      radial thermistor temperature to tip thermistor temperature for 3 catheter
      orientations in vitro resulted in tip thermistor underestimation of peak
      electrode-tissue interface temperature by a median of 0.5 degrees C in 35% of the
      perpendicular orientations, 1.9 degrees C in 82% of the 45 orientations, and 5
      degrees C in 83% of the parallel orientations. During in vivo trials, the tip
      thermistor underestimated the peak electrode-tissue interface temperature during
      2 of 51 lesions by 1.2 degrees C and 7.6 degrees C. There was a sudden rise in
      electrical impedance in 17 of 51 radiofrequency energy deliveries. Only one case
      was observed where the peak electrode-tissue interface temperature was below 95
      degrees C. The normal to extended tip thermistor configurations analysis showed
      similar relationships between lesion size and temperature. CONCLUSIONS: Accuracy
      of a single tip thermistor was found to be dependent upon catheter-tissue
      orientation. With routine catheter positioning in vivo, the tip thermistor was a
      good indicator of peak electrode-tissue interface temperature. Thus with power
      regulation to avoid temperatures greater than 90 degrees C, a single flush
      mounted tip thermistor is probably adequate for temperature monitoring of lesion
      formation and avoidance of impedance rises.

PMID- 7647953
TI  - Early afterdepolarization abolished by potassium channel opener in a patient with
      idiopathic long QT syndrome.
AB  - We describe a 17-year-old boy with idiopathic long QT syndrome and repeated
      syncopal episodes. Early afterdepolarization (EAD) in the monophasic action
      potential (MAP) was demonstrated in the posterior septum of the left ventricle.
      Injection of the potassium channel opener nicorandil decreased EAD and shortened
      MAP duration. The syncopal episodes due to ventricular fibrillation disappeared
      after administration of the potassium channel opener.

PMID- 7647954
TI  - Neural control of the heart: the importance of being ignorant.

PMID- 7647955
TI  - Models of atrial reentry.

PMID- 7647957
TI  - 3rd International Congress on Biological Response Modifiers. Cancun, Mexico,
      January 26-29, 1995. Abstracts.

PMID- 7647956
TI  - Effects of interleukin-1 alpha administration on pituitary-adrenal and pituitary
      thyroid axes function of patients with ovarian cancer.
AB  - We monitored pituitary, adrenal, and thyroid function in 21 women who had
      recurrent ovarian cancer and who received interleukin-1 alpha (IL-1 alpha) before
      and after carboplatin. Serum cortisol, corticotropin, thyroxine, and thyrotropin
      were measured in the morning before and at the end of each treatment cycle. Serum
      corticotropin levels were suppressed in many patients despite a normal
      simultaneous serum cortisol; thyrotropin tended to rise with declining thyroxine
      levels after prolonged IL-1 alpha administration. However, serum cortisol and
      thyroxine remained within the normal range at all times, in all patients. Thyroid
      dysfunction consistent with thyroiditis was seen in one patient. We conclude that
      administration of IL-1 alpha as currently used in clinical studies does not
      create significant thyroid or adrenocortical dysfunction.

PMID- 7647959
TI  - Enhanced susceptibility of c-myc antisense oligonucleotide-treated human renal
      cell carcinoma cells to lysis by peripheral blood lymphocytes.
AB  - C-myc oncogene expression has been implicated in the poor prognosis of human
      renal cell carcinoma (RCC), and these tumor cells are resistant to cytotoxic
      effector cells. We hypothesized that the resistance of RCC cells to lysis by
      cytotoxic effector lymphocytes might be regulated by c-myc expression. The
      present study tested this hypothesis by examining the effect of c-myc antisense
      oligonucleotide treatment on the susceptibility of RCC to lysis by cytotoxic
      lymphocytes. The Caki-1 human RCC cell line constitutively expresses c-myc mRNA,
      and treatment with c-myc antisense oligonucleotide resulted in a significant
      inhibition of the expression of c-myc mRNA and enhanced susceptibility to lysis
      by peripheral blood lymphocytes (PBL). The enhanced susceptibility to lysis was
      observed by PBL derived from both normal donors and patients with RCC. The
      susceptibility of c-myc antisense oligonucleotide-treated Caki-1 cells to lysis
      by lymphokine-activated killer (LAK) cells, natural killer (NK) cells, and tumor
      infiltrating lymphocytes (TIL) was also enhanced. Furthermore, enhanced
      susceptibility was also seen when freshly isolated autologous tumor cells were
      used as target cells. The mechanism of the enhanced susceptibility of c-myc
      antisense oligonucleotide-treated Caki-1 cells to lysis was examined. No effect
      was observed on the expression of major histocompatibility complex (MHC) class I
      and MHC class II on the tumor cells. However, there was a modest increase in the
      frequency of effector-target binding. Further, c-myc antisense oligonucleotide
      treated Caki-1 cells were more susceptible to lysis by tumor necrosis factor
      alpha (TNF-alpha). The findings of this study demonstrate that c-myc antisense
      oligonucleotide directly affects established RCC cells and freshly isolated RCC
      cells by rendering them more susceptible to lysis by PBL, LAK cells, NK cells,
      and T lymphocytes. The enhanced susceptibility may be due in part to the enhanced
      sensitivity to TNF-alpha and to the augmentation of PBL binding to tumor cells.
      The possible clinical implications of these findings are discussed.

PMID- 7647958
TI  - Role of interferon-gamma in mediating the antitumor efficacy of interleukin-12.
AB  - Although interleukin-12 (IL-12) has marked antitumor activity against the murine
      Renca renal cell carcinoma in vivo, no antiproliferative activity with IL-12 was
      observed against these tumor cells in vitro; in contrast, interferon-gamma (IFN
      gamma) had growth inhibitory activity. Since one of the properties of IL-12 is
      its ability to stimulate production of IFN-gamma, the role of IFN-gamma in
      mediating the antitumor activity of IL-12 was evaluated. Substantially diminished
      antitumor activity was observed in mice injected with IL-12 and neutralizing
      antibody to murine IFN-gamma compared with mice receiving IL-12 alone, indicating
      that IFN-gamma was required for the optimal antitumor efficacy of IL-12. However,
      several lines of investigation suggest that the antitumor effect of IL-12 is not
      mediated solely through the induction of IFN-gamma. Exogenous administration of
      IFN-gamma to Renca tumor-bearing euthymic mice resulted in less antitumor
      efficacy than that which could be obtained with IL-12. In addition, the antitumor
      effect of IL-12 was reduced in nude mice compared with euthymic mice, but an
      approximately 10-fold higher level of serum IFN-gamma was induced in nude than in
      euthymic mice. Thus, these results indicate that induction of high serum levels
      of IFN-gamma is not sufficient to mediate the antitumor efficacy of IL-12.

PMID- 7647960
TI  - Cellular characterization and retroviral transduction of short-term breast cancer
      cells.
AB  - The effort to develop cell lines from surgical specimens has been a difficult
      goal for years. We derived short-term primary human mammary carcinoma cell lines
      from breast tumors in 20 of 23 patients. Morphologically, cultured cells showed
      small cells with high nuclear cytoplasmic ratio and larger cells with abundant
      dense cytoplasm. The nuclei were round to oval with one to four nucleoli.
      Immunocytochemically, the cells stained positive for keratin. Tumor cells showed
      phenotypic overexpression of the breast tumor-associated antigen DF3 compared
      with normal mammary epithelial cells. The doubling time of tumor cells in vitro
      ranged from 2.6 to 3.6 days. The cultured cells were characterized as mammary
      carcinoma cells by their tumorigenicity in nude mice. Of 14 of the 23 short-term
      cell lines tested, 5 grew in nude mice and eventually regressed, 3 grew
      progressively in nude mice, and the remaining 6 did not grow within 3 months. To
      examine the feasibility of cytokine gene transfer into human mammary carcinoma
      cells, we introduced the cDNA for human tumor necrosis factor-alpha (TNF-alpha)
      into short-term cell lines with a retroviral vector. In our short-term primary
      breast cancer cell lines derived from breast tumors, TNF-alpha secretion ranged
      between 89 ng/10(6) cells/48 h and 479 ng/10(6) cells/24 h. These findings
      indicate that short-term primary human mammary carcinoma cell lines can be grown
      consistently from breast tumors, and that retroviral mediated-cytokine gene
      transfer into short-term human mammary carcinoma cells is feasible and may be of
      potential use in immunotherapy trials.

PMID- 7647961
TI  - Enhancement of immunostimulatory activity by dual substitution of C8-substituted
      guanine ribonucleosides: correlation with increased cytokine secretion.
AB  - Guanine ribonucleosides with single substitutions at the C8 position
      (monosubstituted) or with dual substitutions at the C8 and N7 positions
      (disubstituted) up-regulate a spectrum of immunologic responses, including
      cytolytic responses to tumor cells. The current studies were undertaken to
      determine the effects of dual substitution on a number of nucleoside-inducible
      immunological parameters. To do so, two monosubstituted analogues, 8
      bromoguanosine and 8-mercaptoguanosine, were directly compared with two
      disubstituted analogues, 7-methyl-8-oxoguanosine and 7-allyl-8-oxoguanosine
      (loxoribine). All of the compounds enhance natural killer (NK) activity,
      lymphocyte proliferation, and antibody production in dose-dependent fashion.
      However, the potency and maximal activity of the disubstituted analogues are
      considerably greater than those of the monosubstituted analogues. Spleen cells
      stimulated for 48 h with the disubstituted compounds produce immunoreactive
      interleukin (IL) 1 alpha, IL-6, tumor necrosis factor-alpha (TNF alpha), and
      interferon-gamma (IFN gamma). Monosubstituted analogues induce lower quantities
      of IL-6, TNF alpha, and IFN gamma and fail to induce detectable levels of IL-1
      alpha. Total IFN activity, assessed by viral inhibition assay, is also lower for
      the monosubstituted analogues. Augmentation of antibody secretion by B cells is
      diminished for neither mono- nor disubstituted compounds upon incubation with
      anti-cytokine antibodies. In contrast, anti-IFN alpha beta markedly reduces the
      effects of monosubstituted analogues on NK activity but has less marked effects
      on NK induction by the disubstituted compounds. A similar pattern of differences
      is seen for lymphocyte proliferation. Thus, although the analogues induce
      synthesis of several cytokines, to date only IFN alpha beta appears directly
      involved in enhancement of NK activity and lymphocyte proliferation. The present
      data do not, however, exclude the existence of an autocrine stimulatory mechanism
      not susceptible to inhibition by anti-cytokine antibodies.

PMID- 7647962
TI  - Effect of a 5-HT1 receptor agonist, CP-122,288, on oedema formation induced by
      stimulation of the rat saphenous nerve.
AB  - Neurogenic oedema formation in the rat hind paw skin induced by electrical
      stimulation of the saphenous nerve and measured by extravasation of [125I]
      albumin, was inhibited by the 5-HT1B receptor agonist, CP-93,129, and the novel
      tryptamine analogue, CP-122,288. Significant inhibition of up to 66% of control
      was observed with CP-122,288 (2 x 10(-14) - 2 x 10(-7) mol kg-1) and CP-93,129 (5
      x 10(-7) - 5 x 10(-6) mol kg-1), with the minimum effective dose for CP-122,288
      being about 10(7) fold less than that for CP-93,129. Oedema formation induced by
      the intradermal administration of exogenous mediators (substance P and histamine)
      in rat dorsal skin was not inhibited by CP-122,288 (2 x 10(-10) mol kg-1). These
      results suggest that CP-122,288 is a potent inhibitor of neurogenic inflammation
      in rat skin and that the effect may be due to a prejunctional inhibition of
      neuropeptide release.

PMID- 7647963
TI  - Regulation of cytosolic calcium by collagen in single human platelets.
AB  - 1. There is controversy in the literature as to whether collagen is able to
      induce directly a rise in cytosolic calcium concentration ([Ca2+]i) in human
      platelets. We have addressed this question by observing the cytosolic calcium
      response of single fura-2-loaded human platelets settling onto a collagen-coated
      surface using dynamic fluorescence ratio imaging. 2. Following a short lag phase
      after adherence to collagen fibres, platelets underwent a rapid rise in cytosolic
      calcium from basal values of 80 +/- 13 nM (n = 24) to a peak of 475 +/- 42 nM (n
      = 24) which was sustained for the remaining period of the experiment. 3. The
      tyrphostin protein tyrosine kinase inhibitor, ST271, reduced substantially the
      proportion of platelets which exhibited a rise in [Ca2+]i on adherence to
      collagen and transformed the response in remaining cells to one of oscillations.
      4. In contrast, and as a control for collagen, laminin-coated surfaces induced
      adherence of human platelets without elevating intracellular [Ca2+]; the cells
      however remained responsive to ADP. 5. We conclude that collagen directly induces
      a rise in cytosolic calcium in single human platelets through a tyrosine kinase
      mediated pathway.

PMID- 7647964
TI  - Characterization and distribution of putative 5-ht7 receptors in guinea-pig
      brain.
AB  - 1. In the presence of (-)-cyanopindolol (1.0 microM) and sumatriptan (1.0
      microM), 0.5 nM [3H]-carboxamidotrytamine ([3H]-5-CT) labelled a single
      population of receptors in guinea-pig cerebral cortex membranes. 2. 5-HT
      displaceable binding was rapid, saturable and reversible. A high affinity binding
      site was characterized both by equilibrium saturation (Kd = 0.76 +/- 0.28 nM;
      Bmax = 68.1 +/- 26.7 fmol mg-1 protein) and kinetic (Kd = 0.18 +/- 0.05 nM)
      analysis. The pharmacological profile of this site was similar to the profile
      obtained in transfected CHO-K1 cells expressing guinea-pig 5-ht7 receptors. 3.
      Autoradiographic analysis revealed a discrete localization of binding sites in
      guinea-pig brain, with the highest density of sites in the medial thalamic nuclei
      and related limbic and cortical regions. Moderate levels of binding were detected
      in sensory relay nuclei, substantia nigra, hypothalamus, central grey and dorsal
      raphe nuclei. This distribution corresponded to that observed using in situ
      hybridization with [35S]-UTP labelled riboprobes complementary to mRNA encoding
      the guinea-pig 5-ht7 receptor. 4. In conclusion, under appropriate conditions,
      [3H]-5-CT labelled a single population of saturable binding sites that
      corresponded to an endogenous 5-ht7 receptor in guinea-pig brain. The
      distribution of 5-ht7 receptors in thalamocortical and limbic brain regions
      suggests a role for these receptors in sensory and affective behaviours.

PMID- 7647965
TI  - Calcium homeostasis in mouse fibroblast cells: affected by U-73122, a putative
      phospholipase C beta blocker, via multiple mechanisms.
AB  - 1. The inhibitory effects of the putative phospholipase C beta inhibitor, U
      73122, on ligand-induced and thapsigargin-induced [Ca2+]i transients were
      investigated in mouse fibroblast cells (the L line). 2. Ca2+ release from
      intracellular stores was stimulated either by ATP (and also by UTP or ADP)
      working through the activation of a P2U receptor, or by lysophosphatidic acid,
      which elicited a more pronounced response. 3. U-73122 inhibited the Ca2+
      mobilization produced by all the agonists in a dose-dependent manner, consistent
      with a mode of action involving phospholipase C inhibition. 4. In addition,
      however, U-73122 slowed the kinetics of intracellular Ca2+ release induced by the
      Ca(2+)-ATPase inhibitor, thapsigargin, and reduced the influx of Ca2+ across the
      plasma membrane, following stimulation of store-dependent influx by the latter.
      5. We conclude that U-73122 has multiple sites of action, all of which can lead
      to a change in Ca2+ homeostasis. Thus, particular caution is recommended when
      employing this agent and when interpreting the results obtained.

PMID- 7647966
TI  - Time-dependent fading of the activation of KATP channels, induced by aprikalim
      and nucleotides, in excised membrane patches from cardiac myocytes.
AB  - 1. The effects of the potassium channel opener (KCO) aprikalim (RP 52891) on the
      nucleotide-induced modulation of ATP-sensitive K+ (KATP) channels in freshly
      dissociated ventricular myocytes of guinea-pig heart, were studied by use of the
      inside-out patch-clamp technique. The internal surface of the excised membrane
      patch was initially bathed with a standard solution (Mg(2+)-free with EDTA), then
      sequentially superfused with solutions containing nucleoside diphosphates (NDPs:
      200 microM ADP and 50 microM GDP) and NDPs plus 1 mM MgCl2 (with EGTA; referred
      to as Mg-NDP solution). 2. The normalized concentration-response (channel
      closing) relationship to ATP was shifted to the right when the standard solution
      was replaced by the Mg-NDP solution. Hence, the internal concentration of ATP
      ([ATP]i) inhibiting the channel activity by half (Ki) increased from 56 microM to
      180 microM, with an apparently constant slope factor (s = 2.37). NDPs in the
      absence of Mg2+ did not decrease the sensitivity of the channels to ATP. 3. In
      standard solution, aprikalim (100 microM) activated KATP channels in the presence
      of a maximally inhibitory [ATP]i (500 microM). This effect was strongly enhanced
      when aprikalim was applied to patches exposed to Mg-NDP solution, as demonstrated
      by the 9 fold increase in Ki for [ATP]i (from 180 microM to 1.5 mM and s = 2.37).
      4. The ability of aprikalim to overcome the channel closing effects of ATP in Mg
      NDP solution waned rapidly. Similarly, the NDP-induced activation of ATP-blocked
      channels was also time-dependent. Both activation processes disappeared before
      the channel run-down phenomenon appeared in ATP-free conditions. 5. In
      conclusion, aprikalim is much more potent in opening KATP channels in membrane
      patches bathed in Mg-NDP solution than in standard solution. However, under the
      former experimental conditions, the effect of aprikalim waned rapidly. It is
      proposed that the waning phenomenon results from changes in the intrinsic
      enzymatic activity of the KATP channel protein (possibly linked to the
      experimental conditions) which lead to the channel closure.

PMID- 7647967
TI  - Caffeine-evoked, calcium-sensitive membrane currents in rabbit aortic endothelial
      cells.
AB  - 1. Single cell photometry and whole-cell patch clamp recording were used to study
      caffeine-induced intracellular Ca2+ signals and membrane currents, respectively,
      in endothelial cells freshly dissociated from rabbit aorta. 2. Caffeine (5 mM)
      evoked a transient increase in [Ca2+]i in fura-2-loaded endothelial cells.
      Pretreatment of cells with 10 microM ryanodine did not alter resting [Ca2+]i but
      irreversibly inhibited the caffeine-induced rise in [Ca2+]i. The caffeine-induced
      increase in [Ca2+]i was not attenuated by the removal of extracellular Ca2+ and
      did not stimulate the rate of Mn2+ quench of fura-2 fluorescence. 3. Bath
      application of caffeine evoked a dose- and voltage-dependent outward current. The
      rate of onset and amplitude of the caffeine-evoked outward current increased with
      higher caffeine concentrations and membrane depolarization. The relationship
      between caffeine-evoked current amplitude and membrane potential was non linear,
      suggesting that the channels underlying the current are voltage-sensitive. 4. In
      the absence of extracellular Ca2+, the amplitude of the caffeine-evoked outward
      current was reduced by approximately 50% but the duration of the current was
      prolonged compared to that observed in the presence of external Ca2+. Ca(2+)-free
      external solutions produced an unexpected increase in both the frequency and
      amplitude of spontaneous transient outward currents (STOCs). 5. Inclusion of
      heparin (10 micrograms ml-1) in the patch pipette abolished the acetylcholine
      (ACh)-induced outward current but failed to inhibit either STOCs or the caffeine
      evoked outward current in native endothelial cells. In the absence of
      extracellular Ca2+, heparin did not affect either STOCs or the caffeine-induced
      outward current. 6. Externally applied tetraethylammonium ions (TEA, 3-10mM)
      reversibly inhibited unitary Ca2+-activated K+ currents and STOCs in endothelial
      cells but failed to inhibit completely the outward current evoked by 20 mM
      caffeine.7. Bath application of 0.1 mM zinc ion (Zn2+), a chloride channel
      blocker, did not affect unitary currents or STOCs but reduced the amplitude of
      the caffeine-evoked current by >75% compared to control. Replacement of
      extracellular NaCl with Na gluconate also reduced the amplitude of the caffeine
      induced outward current. Bath application of 0.1 mM Zn2+ and 10 mM TEA completely
      blocked the caffeine-evoked outward current in endothelial cells.8. Caffeine
      induced Ca2+ release from intracellular stores evokes a transient rise in [Ca2+1,
      which is correlated with a large, transient outward current. The ionic dependence
      and inhibition of the caffeine sensitive current by TEA and Zn2+ suggests that
      Ca2+-activated K+ and Cl- conductances contribute to the caffeine response in
      rabbit aortic endothelial cells.

PMID- 7647968
TI  - Characterization of alpha 1-adrenoceptor subtypes in tension response of human
      prostate to electrical field stimulation.
AB  - 1. The effects of various alpha 1-adrenoceptor antagonists and nifedipine on
      tension responses of human prostate to electrical field stimulation were
      evaluated in this study. 2. Prazosin (3 x 10(-10) to 10(-8) M) and 5-methyl
      urapidil (10(-9) to 3 x 10(-8) M) blocked concentration-dependently the tension
      responses to electrical field stimulation and completely abolished them in the
      maximal concentrations (10(-8) M and 3 x 10(-8) M, respectively); in contrast,
      chloroethylclonidine (CEC), in the maximal concentration of 100 microM, blocked
      these effects by only 50%. 3. The contractile responses of rat vas deferens and
      spleen to exogenously-applied alpha 1-adrenoceptor agonists were competitively
      inhibited by prazosin and 5-methyl-urapidil; in addition, the pA2 values were
      calculated and the relative potencies with reference to prazosin were obtained.
      The relative potency of 5-methyl-urapidil in human prostate (0.105) was close to
      that in rat vas deferens (0.257), which contains primarily putative alpha 1A
      adrenoceptors. However, it was much more than that in rat spleen (0.011), which
      contains primarily putative alpha 1B-adrenoceptors. 4. Nifedipine (10(-8) to 10(
      6) M) inhibited concentration-dependently the contractile responses to electrical
      field stimulation in human prostate; in addition, the inhibition percentages were
      similar to those to exogenously-applied noradrenaline in rat vas deferens. In
      contrast, CEC (10 microM), which almost flattened the concentration-response
      curve of the rat spleen to phenylephrine, only partially inhibited (by 33.1%) the
      nerve-mediated contraction of human prostate. 5. The involvement of prejunctional
      alpha 2-adrenoceptors situated on the sympathetic nerve terminals of human
      prostate was also examined. Clonidine (3 x 10-9 to 3 x 10- M) blocked
      concentration-dependently the contractile response to electrical field
      stimulation of human prostate and this inhibitory effect was reversed by
      yohimbine (10-7 M). Additionally, the inhibitory effect of CEC (3 x 10-6 to 3 x
      10-4 M)to the nerve-mediated contraction was also partially reversed by yohimbine
      (10-7 M).6. It is suggested that the putative czA-adrenoceptors in human prostate
      may be functionally confined to the synaptic region whereas only minor
      populations of the putative alpha 1B- and/or alpha 1c-adrenoceptors exist in this
      region.

PMID- 7647970
TI  - Ginsenosides-induced nitric oxide-mediated relaxation of the rabbit corpus
      cavernosum.
AB  - 1. Ginsenosides, the active ingredients extracted from Panax ginseng, have been
      shown to promote nitric oxide (NO) release in bovine aortic endothelial cells.
      Since the endothelial cells and the perivascular nerves in penile corpus
      cavernosum contain NO synthase and an NO-like substance has been shown to be
      released from these cells which relaxes corpus cavernosum, the possibility that
      ginsenosides may relax corpus cavernosum by releasing endogenous NO was examined.
      2. With an in vitro tissue superfusion technique, ginsenosides (250, 500 and 750
      micrograms ml-1) relaxed corpus cavernosum, concentration-dependently. 3. Using
      an in vitro tissue bath technique, acetylcholine (ACh)-induced relaxations were
      increased in the presence of ginsenosides (250 micrograms ml-1). 4. Ginsenosides
      at 100 micrograms ml-1 significantly enhanced the tetrodotoxin (TTX)-sensitive
      relaxation of corpus cavernosum elicited by transmural nerve stimulation. 5. The
      ginsenosides-induced, ACh-induced and ginsenosides-enhanced transmural nerve
      stimulation-elicited relaxations were significantly attenuated by NG-nitro-L
      arginine (100 microM) and oxyhaemoglobin (oxyHb; 5-10 microM), and were enhanced
      by superoxide dismutase (SOD; 50 u ml-1). 6. The relaxations and their
      attenuation by NG-nitro-L-arginine and TTX were associated with increase and
      decrease in tissue cyclic GMP levels, respectively. 7. It is concluded that
      ginsenosides may release NO from endothelial cells, and enhance NO release from
      endothelial cells elicited by other vasoactive substances and from perivascular
      nitrergic nerves in the corpus cavernosum. These endothelial and neurogenic
      effects of ginsenosides in inducing relaxation of the corpus cavernosum may
      account for the aphrodisiac effect of Panax ginseng.

PMID- 7647969
TI  - Effects of GTP gamma S on muscarinic receptor-stimulated inositol phospholipid
      hydrolysis in permeabilized smooth muscle from the small intestine.
AB  - 1. Smooth muscle fragments from the longitudinal layer of the small intestine of
      the guinea-pig were permeabilized with Staphylococcus aureus alpha toxin (alpha
      toxin) and used to investigate the role of G-protein activation in the regulation
      of muscarinic acetylcholine receptor (AChR)-stimulated inositol phospholipid
      hydrolysis. 2. The efficiency of alpha-toxin permeabilization was estimated by
      the release of [3H]-2-deoxyglucose ([3H]-2DG) after prior loading or lactate
      dehydrogenase (LDH) enzyme release from the smooth muscle fragments. 3. In alpha
      toxin-permeabilized smooth muscle, but not in non-permeabilized muscle, GTP gamma
      S induced time- and concentration-dependent increases in labelled inositol
      phosphates. Carbachol (CCh) increased labelled inositol phosphates in both
      permeabilized and non-permeabilized muscle, although the increases were greater
      in non-permeabilized smooth muscle. The response to 100 microM CCh was severely
      reduced by 0.5 microM atropine. 4. In permeabilized muscle the effects of GTP
      gamma S or CCh on inositol phosphate levels were reduced by treatment with
      pertussis toxin (PTX) and completely inhibited by GDP beta S. 5. GTP gamma S
      caused a concentration-dependent inhibition of the CCh-induced increases in the
      levels of labelled inositol phosphates. Dibutyryl cyclic AMP or Sp-cAMPs
      (adenosine-3',5'-cyclic phosphorothiolate-Sp) reduced the effects of CCh on
      inositol phosphate levels. 6. The results suggest that muscarinic AChR activation
      induces inositol phospholipid hydrolysis via more than one G-protein in this
      smooth muscle and that several mechanisms may contribute to the modulation of
      both stimulatory and inhibitory responses observed.

PMID- 7647971
TI  - Pharmacological identification of different inhibitory mediators involved in the
      innervation of the internal anal sphincter.
AB  - 1. Inhibitory non-adrenergic, non-cholinergic (NANC) responses were studied in
      isolated strips from the rabbit internal anal sphincter. 2. In the presence of
      atropine and guanethidine, transmural field stimulation induced frequency
      dependent relaxations that reached a plateau at frequencies > or = 4 Hz. 3. These
      relaxations were inhibited by apamin (10(-6) M) and by N omega-nitro-L-arginine
      (L-NOARG, 10(-4) M). With these two substances in combination, relaxations were
      still seen in response to field stimulation, but only at frequencies > 2 Hz. 4.
      In the presence of both apamin (10(-6) M) and L-NOARG (10(-4) M), responses at
      high frequencies consisted of a fast relaxation followed by a slow return to
      prestimulus tension level. alpha-Chrymotrypsin hastens the return of tension to
      prestimulus level after high frequency stimulation. 5. Zinc-protoporphyrin IX, an
      inhibitor of haeme oxygenase, had a significant inhibitory effect on relaxations
      induced by transmural field stimulation. It was found, however, that responses to
      sodium nitroprusside and to isoprenaline (both 10(-9)-10(-4) M) were reduced
      comparably, indicating that the effect of zinc-protoporphyrin IX was unspecific.
      6. It is concluded that pharmacological analysis allows identification of at
      least three distinguishable components of the inhibitory NANC innervation of the
      rabbit internal anal sphincter. The study does not allow conclusions about the
      role of carbon monoxide, a recently proposed mediator of NANC responses in
      opossum internal anal sphincter.

PMID- 7647972
TI  - Differences in response to 5-HT4 receptor agonists and antagonists of the 5-HT4
      like receptor in human colon circular smooth muscle.
AB  - 1. In isolated circular smooth muscle strips of human colon 5-hydroxytryptamine
      (5-HT) produced a concentration-related inhibition of spontaneous motility. 2.
      The azabicycloalkyl benzimidazolones, BIMU 8 and BIMU 1, which have 5-HT4
      receptor stimulant properties, inhibited motility with EC50 values of 0.76 microM
      and 3.19 microM respectively and their Emax values were not significantly
      different from 5-HT (EC50, 0.13 microM). 3. The 5-HT4 receptor antagonist, DAU
      6285 (1-10 microM), displaced the 5-HT concentration-response curve to the right
      in a parallel concentration-dependent manner without depressing the maximum. The
      Schild plot was linear and the slope did not differ significantly from unity
      giving a pA2 value of 6.32. 4. The high affinity selective 5-HT4 receptor
      antagonist, GR 113808, at a concentration of 3 nM displaced the 5-HT
      concentration-response curve in a parallel manner giving an apparent pKB estimate
      of 8.9 +/- 0.24. However, higher concentrations of 10-100 nM GR 113808 did not
      result in a further significant displacement of the 5-HT concentration-response
      curve and there was no suppression of Emax. 5. GR 113808 (10 nM) also caused a
      parallel displacement of the concentration-response curve to the 5-HT4 receptor
      agonist, 5-methoxytryptamine (5-MeOT) giving apparent pKB values ranging from 8.3
      9.3. 6. GR 113808 (3-100 nM) failed to displace 5-HT or 5-MeOT concentration
      response curves in tissue strips from 3 patients out of a total of 10 patients
      studied in whom the response to 5-HT and 5-MeOT was normal. 7. The 5-HT4 receptor
      antagonist, SDZ 205-557 (0.3-10 microM), had no significant effect on 5-HT
      induced inhibition of spontaneous motility.8. The present results are discussed
      in the light of variability of response to GR 113808 and SDZ205-557 in other
      tissues.9. Overall, our data indicate that human colon circular smooth muscle can
      be regarded as a site in which 5-HT4-like receptors are present but it is as yet
      unclear whether these results are also an indication of receptor variation.

PMID- 7647973
TI  - A study on P2X purinoceptors mediating the electrophysiological and contractile
      effects of purine nucleotides in rat vas deferens.
AB  - 1. We have studied both the electrophysiological and contractile effects of the
      purine nucleotide, adenosine-5'-triphosphate (ATP), as well as a number of its
      structural analogues as agonists at P2X purinoceptors in the rat vas deferens in
      vitro. 2. Electrophysiological effects were investigated by a whole cell voltage
      clamp technique (holding potential-70 mV) with fast flow concentration-clamp
      applications of agonists in single isolated smooth muscle cells. ATP, 2
      methylthio adenosine-5'-triphosphate (2-MeSATP) and alpha,beta methylene
      adenosine-5'-triphosphate (alpha,beta-meATP) all evoked inward currents over a
      similar concentration range (0.3-10 microM), being approximately equipotent with
      similar concentrations for threshold effects (0.3 microM). ADP (10 microM) also
      evoked a rapid current of similar peak amplitude to that seen with ATP (10
      microM). 3. alpha,beta-meATP was the most potent agonist in producing
      concentrations of the rat vas deferens whole tissue preparation, with a threshold
      concentration equal to that in the electrophysiological studies (0.3 microM).
      However, ATP and 2-MeSATP were at least ten times less potent in studies
      measuring contraction than in the electrophysiological studies. Furthermore,
      their concentration-effect curves were shallow with smaller maximal responses
      than could be achieved with alpha,beta-meATP. ADP, AMP and adenosine were
      inactive at concentrations up to 1 mM. The rank order of agonist potencies
      observed for contraction was alpha,beta-meATP >> ATP = 2-MeSATP. 4. Measurement
      of inorganic phosphate (iP), as a marker of purine nucleotide metabolism in the
      vasdeferens whole tissue preparation, indicated that ATP and 2-MeSATP were
      rapidly metabolized,whereas alpha,beta-meATP was stable for up to 2 h. Removal of
      divalent cations prevented breakdown of ATP and 2-MeSATP, suggesting that
      metabolism involved a Ca2+/Mg2+-dependent enzyme.5. It appears that in isolated
      preparations of rat vas deferens, the low potency of ATP and 2-MeSATP can be
      explained by rapid agonist breakdown by ectonucleotidases. However, this is not
      the case in the single cell studies where the use of rapid concentration-clamp
      applications revealed the true potency of the agonists. Under such conditions the
      three agonists were all equal in potency indicating that the rank order of
      agonist potencies of alpha,beta-meATP>> ATP = 2-MeSATP is not in fact
      characteristic of smooth muscle P2x-purinoceptors as commonly believed.

PMID- 7647974
TI  - Inhibition by zinc protoporphyrin-IX of receptor-mediated relaxation of the rat
      aorta in a manner distinct from inhibition of haem oxygenase.
AB  - 1. Carbon monoxide (CO), produced by haem oxygenase through degradation of haem,
      has been claimed to be a neuromessenger and a possible regulator of vascular
      tone. We examined whether the haem oxygenase inhibitor, zinc protoporphyrin-IX
      (ZnPP) and other porphyrins affect the relaxation evoked by various agents in the
      rat isolated aorta. 2. Pretreatment with ZnPP (0.1 mM) virtually abolished the
      relaxation evoked by vasoactive intestinal peptide (VIP) and atrial natriuretic
      peptide (ANP). ZnPP also evoked a rightward shift of the concentration-response
      curve for the relaxation induced by acetylcholine. 3. In contrast, ZnPP did not
      affect the relaxation evoked by forskolin and 3-morpholino-sydnonimine, agents
      which directly activate adenylate and guanylate cyclase, respectively. 4.
      Although, less effective than ZnPP, tin protoporphyrin-IX (SnPP; 0.1 mM) and
      protoporphyrin-IX (PP; 0.1 mM) also attenuated the VIP-evoked relaxation. 5. The
      elevation of cyclic AMP and cyclic GMP levels evoked by VIP and ANP,
      respectively, were abolished by pretreatment with ZnPP (0.1 mM). 6. ZnPP, SnPP
      and PP did not affect the contraction evoked by phenylephrine. 7. The results
      show that ZnPP inhibits relaxation induced by VIP, ANP and acetylcholine,
      probably by interfering with membrane receptor-coupled signal transduction
      pathways. This inhibition does not seem to be dependent upon inhibition of haem
      oxygenase. The lack of specificity of the haem oxygenase inhibiting
      metalloporphyrins makes them less suitable as pharmacological tools in the
      investigation of a messenger role for CO.

PMID- 7647975
TI  - Characterization of U-97775 as a GABAA receptor ligand of dual functionality in
      cloned rat GABAA receptor subtypes.
AB  - 1. U-97775 (tert-butyl 7-chloro-4,5-dihydro-5-[(1-(3,4,5
      trimethyl)piperazino)carbonyl]- imidazo[1,5-a])quinoxaline-3-carboxylate) is a
      novel GABAA receptor ligand of dual functionality and was characterized for its
      interactions with cloned rat GABAA receptors expressed in human embryonic kidney
      cells. 2. The drug produced a bell-shaped dose-response profile in the alpha 1
      beta 2 gamma 2 receptor subtype as monitored with GABA-induced Cl- currents in
      the whole cell patch-clamp technique. At low concentrations (< 0.5 microM), U
      97775 enhanced the currents with a maximal increase of 120% as normalized to 5
      microM GABA response (control). An agonist interaction of U-97775 with the
      benzodiazepine site is suggested, because Ro 15-1788 (an antagonist at the
      benzodiazepine site) abolished the current increase and [3H]-flunitrazepam
      binding was inhibited by U-97775 with a Ki of 1.2 nM. 3. The enhancement of GABA
      currents progressively disappeared as the U-97775 concentration was raised above
      1 microM, and the current amplitude was reduced to 40% below the control at 10
      microM U-97775. The current inhibition by U-97775 (10 microM) was not affected by
      Ro 15-1788. It appears that U-97775 interacts with a second site on GABA
      receptors, distinct from the benzodiazepine site, to reverse its agonistic
      activity on the benzodiazepine site and also to inhibit GABA currents. 4. U-97775
      at low concentrations reduced and at high concentrations enhanced [35S]-TBPS
      binding. Ro 15-1788 selectively blocked the effect of U-97775 at low
      concentrations. Analysis of the binding data in the presence of Ro 15-1788
      yielded a single low affinity site with an estimated Kd of 407 nM.5. In other
      alpha beta upsilon receptor subtypes, U-97775 at low concentrations enhanced Cl-
      currents in the alpha 3 beta 2 upsilon 2,but not in the alpha 6 beta 2 upsilon 2
      subtype. On the other hand, U-97775 at high concentrations reduced Cl- currents
      in all the receptor subtypes we examined, including those of two subunits, alpha
      1 beta 2, beta 2 upsilon 2 and alpha 1 upsilon 2 subtypes.6. Therapeutically, U
      97775 could be unique among benzodiazepine ligands because of its ability to
      limit its own agonistic activity such that, at high doses the appearance of
      agonistic activity would be delayed until occupancy of its second site wanes.
      This property should make the total agonistic activity of U-97775 relatively
      constant over a wide range of drug doses, and may minimize its liability to
      abuse.

PMID- 7647976
TI  - ETA receptor-mediated constrictor responses to endothelin peptides in human blood
      vessels in vitro.
AB  - 1. We have characterized the constrictor endothelin receptors present in human
      isolated blood vessels using ETA and ETB selective agonists and antagonists. 2.
      Monophasic dose-response curves were obtained for ET-1 with EC50 values of 6.8 nM
      in coronary artery, 3.9 nM in internal mammary artery, 17.4 nM in pulmonary
      artery, 14.5 nM in aorta and 3.2 nM in saphenous vein. In coronary artery, ET-2
      was equipotent with ET-1 with an EC50 value of 5.7 nM. The non-selective peptide,
      sarafotoxin 6b, was 2-3 times less potent than ET-1 but the maximum responses to
      these two were comparable. 3. In each vessel ET-3 was much less active than ET-1.
      No response was obtained to ET-3 in aorta and pulmonary artery or in up to 50% of
      coronary artery, mammary artery and saphenous vein preparations. In those
      preparations that did respond, dose-response curves were incomplete at 300 nM.
      Variable contractions were also obtained with the ETB-selective agonist,
      sarafotoxin 6c (S6c). Where responses were detected, although S6c was more potent
      than ET-1 (EC50 values of 0.6-1.2 nM), the maximum response produced was always
      less than 20% of that to ET-1. 4. The synthetic ETB agonists, BQ3020 and
      [1,3,11,15Ala]-ET-1, were without effect in any of the five blood vessels at
      concentrations up to 3 microM. 5. ET-1-induced vasoconstriction was blocked by
      the ETA-selective antagonists, BQ123 and FR139317. Schild-derived pA2 values were
      7.0, 7.4 and 6.9 for BQ123 and 7.6, 7.9 and 7.3 for FR139317 in coronary artery,
      mammary artery and saphenous vein, respectively, consistent with antagonism of
      ETA receptors. Slopes of the Schild regressions were not significantly different
      from one. Comparable values of pA2 were estimated for 3ftM BQ123 in aorta (7.4+/
      0.5) and pulmonary artery (6.9) from the Gaddum-Schild equation.6. In conclusion
      we have shown that in human isolated blood vessels, ET-1 is more potent than ET-3
      suggesting the presence of vasoconstrictor ETA receptors. This is supported by
      the lack of effect of the ETB agonists, BQ3020 and [1,3,1,1,15Ala]-ET-l and the
      ability of the ETA antagonists, BQ123 andFR139317 to block ET-1 responses. Some
      preparations did contract in response to low concentrations of the ETB-selective
      sarafotoxin 6c but responses were variable and the maximum was always much less
      than that to ET-1 in the same preparations. Therefore although constrictor ETB
      receptors were present on the smooth muscle of human blood vessels,
      vasoconstriction elicited by the endothelin peptides in vitro is via ETA receptor
      activation.

PMID- 7647977
TI  - Inhibitory action of betaxolol, a beta 1-selective adrenoceptor antagonist, on
      voltage-dependent calcium channels in guinea-pig artery and vein.
AB  - 1. The effects of betaxolol, (+/-)-1-[4-[2-(cyclopropylmethoxy) ethyl] phenoxy]-3
      (isopropylamino)-2-propanol hydrochloride, a beta 1-selective adrenoceptor
      antagonist, on voltage-dependent Ca2+ channels were investigated in single smooth
      muscle cells from guinea-pig mesenteric artery and portal vein using a whole-cell
      variant of the patch-clamp technique. Ca2+ channel currents were recorded with
      bath solutions contained 10 mM Ba2+ for arterial cells and 2 mM Ca2+ for venous
      cells. 2. Betaxolol inhibited Ca2+ channel currents dose-dependently in both
      mesenteric artery cells and portal vein cells. The two isomers, (+)-betaxolol and
      (-)-betaxolol (relative beta-antagonistic efficacies of 0.1 and 1, respectively),
      had similar potencies for inhibiting Ca2+ channel currents in portal vein cells.
      Propranolol did not inhibit the currents. Thus the inhibitory action of betaxolol
      on Ca2+ channel currents was independent of the beta-adrenoceptor. 3. The
      inhibitory action of betaxolol on Ca2+ channel currents was compared with that of
      diltiazem and of nifedipine in mesenteric artery cells. The current inhibition
      depended on the stimulation frequency with all drugs (use-dependent block). All
      drugs also accelerated the current decay and shifted the voltage-dependent
      inactivation curve in a negative direction. 4. In conclusion, betaxolol inhibited
      Ca2+ channel currents in vascular smooth muscle cells. The mode of inhibitory
      action was similar to that of diltiazem and nifedipine. Our results suggest that
      betaxolol is a unique beta-adrenoceptor antagonist that has a direct inhibitory
      action on voltage-dependent Ca2+ channels in vascular smooth muscle cells.

PMID- 7647978
TI  - Drug-induced defaecation in rats: role of central 5-HT1A receptors.
AB  - 1. We investigated the acute effects of 5-hydroxytryptamine (5-HT), and of the 5
      HT1A receptor agonists, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT),
      buspirone and SR 57746A, on rat faecal pellet output and water content. 2. 5-HT,
      8-OH-DPAT, buspirone and SR 57746A, a new selective 5-HT1A receptor agonist,
      displaced [3H]-8-OH-DPAT from specific binding sites in rat hippocampus membranes
      (Ki, nM; 1.8, 1.2, 15, 3.1 respectively) and stimulated rat defaecation dose
      dependently. SR 57746A and buspirone induced 1 g dry weight of faeces at 1.3 and
      6.1 mg kg-1, p.o. (AD1) respectively. 8-OH-DPAT and 5-HT stimulated defaecation
      after s.c. injection (AD1, 0.07 and 7.5 mg kg-1, respectively). All these agents
      increased faecal water content. 3. The putative 5-HT1A receptor antagonist,
      pindolol, injected s.c. or i.c.v., significantly reduced the defaecation induced
      by systemically administered 8-OH-DPAT, buspirone or SR 57746A, but not 5-HT. 4.
      Pretreatment with p-chlorophenylalanine (i.p.) or 5,7-dihydroxytryptamine
      (i.c.v.), according to protocols designed to cause either generalized or CNS
      limited 5-HT depletion respectively, also reduced the defaecation induced by
      buspirone or SR 57746A. 5. No specific 5-HT1A binding sites could be labelled by
      incubating rat colon membranes with [3H]-8-OH-DPAT, and in vitro preparations of
      rat colon segments showed no response to 8-OH-DPAT or SR 57746A up to 5 microM.
      6. After eight days' repeated daily treatment, complete tolerance developed to
      the stimulant effects of SR 57746A and buspirone on faecal water content, but not
      on faecal pellet output. This suggests that faecal mass excretion and water
      exchange through the gut wall are affected by independent mechanisms.7. The
      present findings support the involvement of central 5-HTIA receptors in
      intestinal propulsion and regulation of luminal fluid content, presumably
      accounting for the drug-induced defaecation in rats.

PMID- 7647979
TI  - Intrinsic activity of the non-prostanoid thromboxane A2 receptor antagonist,
      daltroban (BM 13,505), in human platelets in vitro and in the rat vasculature in
      vivo.
AB  - 1. We evaluated the effects of daltroban on (i) human platelet shape change and
      aggregation in vitro, and (ii) mean systemic and pulmonary arterial pressures
      (MAP and MPAP, respectively) as well as haematocrit, in anaesthetized, open-chest
      Sprague-Dawley rats, compared with those of a chemically distinct prostanoid
      thromboxane A2 (TxA2) receptor antagonist, SQ 29,548, and agonist, U-46619. 2. In
      human platelets in vitro, daltroban (10 nM-100 microM; n = 6 per group)
      concentration-dependently induced shape change, attaining at 50 microM, a maximum
      amplitude of 0.83 +/- 0.09 mV representing 46.4 +/- 4.8% of that evoked by U
      46619 (1.78 +/- 0.20 mV at 0.2 microM; n = 9); and inhibited U-46619-induced
      platelet aggregation with an IC50 of 77 (41-161)nM. SQ 29,548 (10 nM-100 microM;
      n = 6 per group) failed to evoke any platelet shape change, but potently
      inhibited U-46619-induced platelet aggregation with an IC50 < 10 nM. 3. In
      anaesthetized rats in vivo, daltroban (10-2500 micrograms kg-1, i.v. infused over
      2 min; n = 4-8 per group) produced a bell-shaped dose-response curve for MPAP and
      haematocrit, and evoked maximal increases of 12.7 +/- 2.1 mmHg and 5.8 +/- 1.5%
      at 80 micrograms kg-1 (n = 6) and 630 micrograms kg-1 (n = 8), respectively (both
      P < 0.05) with ED50s of 20 (16-29) and 217 (129-331) micrograms kg-1,
      respectively. By comparison, U-46619(0.16-20 microg kg-1, i.v.), induced dose
      dependent increases in MPAP and haematocrit (25.4 +/- 1.0 mmHg and 16.1 +/- 2.9%
      at the highest dose; n = 12, both P<0.01), with ED50s of 1.8 (1.3-2.5) and
      3.9(3.5- 5.4) microg kg- 1, respectively. Daltroban dose-dependently increased
      MAP with a maximum amplitude of 42.2 +/- 4.4 mmHg at a dose of 80 microg kg-1
      [ED50 = 94 (64-125) microg kg-1], similar to that induced by U-46619 (41.3 +/-
      9.6 mmHg) at a dose of 0.63 microg kg-1 [ED50= 0.22 (0.13-0.24) microg kg-1]. SQ
      29,548(10-2500 microg kg-1, i.v.; n =4 per group) failed to modify significantly
      any of these parameters.4. Our results clearly demonstrate that daltroban, in a
      similar manner to the TxA2 analogue, U-46619,but unlike the TxA2 receptor
      antagonist, SQ 29,548, exhibits significant intrinsic activity in human platelets
      in vitro and in the rat vasculature in vivo, possibly through TxA2 receptor
      activation.

PMID- 7647980
TI  - Discrimination by benextramine between the NPY-Y1 receptor subtypes present in
      rabbit isolated vas deferens and saphenous vein.
AB  - 1. In order to characterize the neuropeptide Y (NPY) Y1 receptors known to be
      present in rabbit isolated vas deferens and saphenous vein, the pharmacological
      activity of the selective NPY Y1 receptor agonists, [Leu31,Pro34] NPY and various
      other peptide agonists, together with the putative NPY antagonist, benextramine,
      were compared in the two tissues. 2. In rabbit isolated saphenous vein,
      cumulative dose-response curves to various NPY agonists were obtained. All the
      peptides tested caused contractions which developed quite slowly. The rank order
      of potency obtained was: PYY > NPY > [Leu31,Pro34] NPY = NPY2-36 > hPP >> NPY13
      36 = NPY18-36. Incubation with benextramine (BXT) at 100 microM for 30 min
      irreversibly abolished the contractile response to [Leu31,Pro34] NPY but was
      ineffective against NPY18-36-induced contractions. 3. Cumulative dose-response
      curves to [Leu31,Pro34] NPY were performed in the same preparation before and
      after incubation with 100 microM BXT for 20 min in order to inactivate NPY Y1
      receptors. The pKA (-logKA) estimation for [Leu31,Pro34] NPY was 7.60 +/- 0.30
      using the operational model and 7.20 +/- 0.33 using the null method; the
      difference between the two methods was not statistically significant (P = 0.36).
      4. Prostatic segments of rabbit vas deferens were electrically stimulated with
      single pulses. Immediately after stabilization of the contractile response, a
      cumulative dose-response curve to various NPY agonists was obtained in each
      tissue. The rank order of potency for twitch inhibition was: PYY>
      [Leu31,Pro34]NPY > NPY > hPP>NPY2- 36 >>NPY13-36>> NPY 18-36 which indicates the
      presence of a prejunctional NPY Y1 receptor. BXT at 100 microM incubated for 10
      or 60 min did not antagonize the response to[Leu31,Pro34] NPY.5. We conclude that
      rabbit isolated saphenous vein contains a population of post-junctional NPY Y1
      receptors irreversibly blocked by BXT, as well as a population of post-junctional
      NPY Y2 receptors,which are insensitive to BXT. In contrast, the rabbit isolated
      vas deferens express a pre-junctional NPYY1 receptor subtype which is not blocked
      by BXT. Tetramine disulphides such as BXT could be useful tools in classifying
      NPY receptors.

PMID- 7647981
TI  - Multiple pathways underlying endothelium-dependent relaxation in the rabbit
      isolated femoral artery.
AB  - 1. In isolated segments of the rabbit femoral artery stimulated with
      noradrenaline, both acetylcholine (1 nM-10 microM) and the calcium ionophore
      A23187 (1 nM-100 microM) evoked endothelium-dependent smooth muscle relaxation
      and hyperpolarization while bradykinin (0.01-100 nM) had no effect. 2. The nitric
      oxide synthase inhibitors, NG-nitro-L-arginine (L-NOARG; 100 microM; 20 min) or
      NG-nitro-L-arginine methyl ester (L-NAME; 100 microM; 20 min) each abolished the
      hyperpolarization and the majority of the relaxation to acetylcholine (maximal
      response reduced from 96.8 +/- 2.3% to 2.0 +/- 1.4%). 3. The potassium channel
      blocker, glibenclamide (10 microM; 10 min) also abolished the change in membrane
      potential to acetylcholine but did not modify the smooth muscle relaxation. 4. In
      contrast, neither L-NAME nor glibenclamide modified the comparable responses of
      the femoral artery to A23187, which were also unaffected by the cyclo-oxygenase
      inhibitor, indomethacin (10 microM). 5. In artery segments stimulated with
      potassium chloride (25 mM), the maximal change in tension and membrane potential
      evoked by A23187 (100 microM) was significantly reduced from 95.0 +/- 4.5% and
      23.0 +/- 2.0 mV to 69.0 +/- 10.1% and 12.0 +/- 1.5 mV, respectively. Under these
      conditions L-NAME further reduced the relaxation but not the accompanying
      hyperpolarization to A23187. 6. Endothelium-denuded arterial segments sandwiched
      with endothelium-intact 'donor' segments gave qualitatively similar relaxant
      responses to those described above for acetylcholine and A23187. 7. Exogenous
      nitric oxide (0.5-10 microM) stimulated a transient relaxation in pre-contracted
      artery segments, which at concentrations above 5 microM was accompanied by smooth
      muscle hyperpolarization(maximum 8.5 +/- 3.2 mV; n = 4). The hyperpolarization
      but not the relaxation to nitric oxide was abolished by either glibenclamide or
      25 mM potassium.8. These data indicate that in the femoral artery, acetylcholine
      induced relaxation can be attributed solely to the release of nitric oxide from
      the endothelium, which then stimulates relaxation independently of a change in
      smooth muscle membrane potential. In contrast, both the relaxation and
      hyperpolarization evoked by A23187 appear to be mediated predominantly by nitric
      oxide-independent pathways which appear to involve a diffusible factor released
      from the endothelium. The results suggest that this diffusible hyperpolarizing
      factor can be released from endothelial cells in the femoral artery by A23187 but
      not by acetylcholine.

PMID- 7647982
TI  - Suppression of eosinophil function by RP 73401, a potent and selective inhibitor
      of cyclic AMP-specific phosphodiesterase: comparison with rolipram.
AB  - 1. We have investigated the inhibitory potency of RP 73401, a novel, highly
      selective and potent inhibitor of cyclic AMP-specific phosphodiesterase (PDE IV),
      against partially-purified PDE isoenzymes from smooth muscle and the particulate
      PDE IV from guinea-pig eosinophils. The inhibitory effects of RP 73401 on the
      generation of superoxide (.O2-), major basic protein (MBP) and eosinophil
      cationic protein (ECP) from guinea-pig eosinophils have also been studied. 2. RP
      73401 potently inhibited partially-purified cyclic AMP-specific phosphodiesterase
      (PDE IV) from pig aortic smooth muscle (IC50 = 1.2 nM); it was similarly potent
      against the particulate PDE IV from guinea-pig peritoneal eosinophils (IC50 = 0.7
      nM). It displayed at least a 19000 fold selectivity for PDE IV compared to its
      potencies against other PDE isoenzymes. Rolipram was approximately 2600 fold less
      potent than RP 73401 against pig aortic smooth muscle PDE IV (IC50 = 3162 nM) and
      about 250 times less potent against eosinophil PDE IV (IC50 = 186 nM). 3.
      Solubilization of the eosinophil particulate PDE IV increased the potency of
      rolipram 10 fold but did not markedly affect the potency of RP 73401. A similar
      (10 fold) increase in the PDE IV inhibitory potency of rolipram, but not RP
      73401, was observed when eosinophil membranes were exposed to
      vanadate/glutathione complex (V/GSH). 4. Reverse transcription polymerase chain
      reaction (RT-PCR), using primer pairs designed against specific sequences in four
      distinct rat PDE IV subtype cDNA clones (PDE IVA-D), showed only mRNA for PDE IVD
      in guinea-pig eosinophils. PDE IVD was also the predominant subtype expressed in
      pig aortic smooth muscle cells. 5. RP 73401 (Kiapp = 0.4 nM) was 4 fold more
      potent than (+/-)-rolipram (Kiapp = 1.7 nM) in displacing[3H]-(+/-)-rolipram from
      guinea-pig brain membranes.6. In intact eosinophils, RP 73401 potentiated
      isoprenaline-induced cyclic AMP accumulation(EC50 = 79 nM). RP 73401 also
      inhibited leukotriene B4-induced generation of *02- (IC50 = 25 nM), and the
      release of major basic protein (ICo = 115 nM) and eosinophil cationic protein
      (IC50 = 7 nM). Rolipram was 3-14 times less potent than RP 73401.7. Thus RP 73401
      is a very potent and selective PDE IV inhibitor which suppresses eosinophil
      function suggesting that it may be a useful agent for the treatment of
      inflammatory diseases such as asthma. The greatly different inhibitory potencies
      of rolipram against PDE IV from smooth muscle and eosinophils(in contrast to the
      invariable effects of RP 73401) are unlikely to be attributable to diverse PDE IV
      subtypes but suggest distinct interactions of the two inhibitors with the enzyme.

PMID- 7647983
TI  - A comparative study of functional 5-HT4 receptors in human colon, rat oesophagus
      and rat ileum.
AB  - 1. The pharmacological properties of 5-hydroxytryptamine (5-HT), the 5-HT4
      receptor agonists, DAU 6236 and SC 53116 and the 5-HT4 receptor antagonist, GR
      1130808, were studied in the rat oesophagus, rat ileum and human colon. 2. 5-HT
      relaxed the longitudinal muscle of the rat oesophagus and rat ileum and the
      circular muscle of the human colon. Absolute values of relaxation were measured
      and showed the order of the maximum responses, rat oesophagus >> human colon >
      rat ileum with EC50 values of 189 +/- 15 nM, 157 +/- 4 nM, 306 +/- 72 nM,
      respectively. 5-HT also inhibited the spontaneous contractions of the human colon
      with an EC50 value of 119 +/- 1 nM. The effect of 5-HT on the human colon was not
      affected by methysergide (10 microM) or ondansetron (1 microM). 3. The use of the
      uptake and metabolism inhibitors, cocaine (30 microM) and pargyline (100 microM),
      did not increase the potency of 5-HT in the rat oesophagus or human colon. In the
      rat oesophagus, cocaine (30 microM) produced a reduction in carbachol-induced
      tone of 22.2 +/- 0.6% and reduced the 5-HT maximum effect by 52.0 +/- 0.4%. 4.
      The compounds, DAU 6236 and SC 53116, showed a different pattern of potencies and
      efficacies in the rat oesophagus, rat ileum and human colon compared to 5-HT. DAU
      6236 relaxed the human colonic circular muscle with an EC50 value of 129 +/- 16
      nM but its efficacy was less than that of 5-HT. DAU 6236 (1 microM) also
      antagonized the 5-HT-induced relaxation of the human colon with a dose-ratio of
      9.9. In the rat oesophagus and rat ileum, DAU 6236 was inactive in the majority
      of tissues. In the minority of oesophagus tissues that did respond the EC50 value
      was 1.2 +/- 0.7 microM. DAU 6236 also antagonized the effect of 5-HT in the rat
      oesophagus in a non-surmountable fashion. SC 53116 relaxed the rat oesophagus
      with an EC50 value of 91 +/- 4 nM, with an efficacy less than that observed to 5
      HT; however, at 200 nM it did not antagonize the 5-HT-induced relaxation of the
      rat oesophagus. SC 53116 showed no agonist activity in the rat ileum and human
      colon, but at 1 microM it did antagonize the effect of 5-HT in the human colon
      with a dose-ratio of 11.3 +/- 0.3. 5. GR 113808 competitively antagonized the 5
      HT4 receptor-mediated relaxation of the rat oesophagus with a pA2 value of 8.59
      (8.18-9.00) against 5-HT and 9.05 (8.79-9.31) against SC 53116. GR 113808(0.01
      microM) also antagonized the 5-HT-induced relaxation of human colonic circular
      muscle with an apparent pA2 value of 9.02 +/- 0.12. However at 1 microM the
      apparent pA2 value was significantly lower than that measured at 0.01 and 0.1
      microM. GR 113808 (0.01 microM) antagonized the 5-HT4 receptor-mediated
      relaxation of the rat ileum with an apparent pA2 value of 9.30 +/- 0.21.6. In
      conclusion, these studies have shown that the human colon, rat oesophagus and rat
      ileum contain functional 5-HT4 receptors. However, the 5-HT4 receptor agonists
      displayed differences in these tissues making it necessary to be cautious when
      extrapolating from animal to human tissue. This emphasizes the importance of the
      use of human tissue in the development of therapeutic drugs.

PMID- 7647984
TI  - JB-9322, a new selective histamine H2-receptor antagonist with potent gastric
      mucosal protective properties.
AB  - 1. JB-9322 is a selective histamine H2-receptor antagonist with gastric
      antisecretory activity and mucosal protective properties. 2. The affinity of JB
      9322 for the guinea-pig atria histamine H2-receptor was approximately 2 times
      greater than that of ranitidine. 3. In vivo, the ID50 value for the inhibition of
      gastric acid secretion in pylorus-ligated rats was 5.28 mg kg-1
      intraperitoneally. JB-9322 also dose-dependently inhibited gastric juice volume
      and pepsin secretion. In gastric lumen-perfused rats, intravenous injection of JB
      9322 dose-dependently reduced histamine-, pentagastrin- and carbachol-stimulated
      gastric acid secretion. 4. JB-9322 showed antiulcer activity against aspirin and
      indomethacin-induced gastric lesions and was more potent than ranitidine. 5. JB
      9322 effectively inhibited macroscopic gastric haemorrhagic lesions induced by
      ethanol. Intraperitoneal injection was effective in preventing the lesions as
      well as oral treatment. The oral ID50 value for these lesions was 1.33 mg kg-1.
      By contrast, ranitidine (50 mg kg-1) failed to reduce these lesions. In addition,
      the protective effect of JB-9322 was independent of prostaglandin synthesis. 6.
      These results indicate that JB-9322 is a new antiulcer drug that exerts a potent
      cytoprotective effect in addition to its gastric antisecretory activity.

PMID- 7647985
TI  - Electrophysiological actions of phenytoin on N-methyl-D-aspartate receptor
      mediated responses in rat hippocampus in vitro.
AB  - 1. The effects of the anticonvulsant, phenytoin, have been examined on N-methyl-D
      aspartate (NMDA) receptor-mediated population spikes in the CA1 region of the rat
      hippocampus in vitro. 2. The 'conventional' (AMPA receptor-mediated) CA1
      population spike, evoked by electrical stimulation of the Schaffer
      collateral/commissural pathway, was abolished by 5 min treatment with 5 x 10(-6)
      M 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), after which superfusion with a
      nominally Mg(2+)-free Krebs solution (containing 5 x 10(-6) M CNQX) led to the
      appearance of an epileptiform population spike which was fully developed by 30-40
      min. 3. The epileptiform population spike was abolished by the non-competitive
      NMDA antagonist, dizocilpine (1 x 10(-6) M, 20-30 min) and inhibited by the
      competitive NMDA receptor antagonist, D-CPP (IC50 for reducing the amplitude of
      the first spike in the train = 8.3 x 10(-7) M), demonstrating that the response
      was mediated by activation of NMDA receptors and validating its use as an assay
      for antagonists acting at the NMDA receptor/channel complex. 4. Phenytoin (0.1,
      0.3 and 1 x 10(-4) M applied cumulatively for 30 min at each concentration)
      failed to inhibit the NMDA receptor-mediated epileptiform population response (n
      = 7 slices). 5. Phenytoin (3 x 10-6 M to 1 x 10-4M) attenuated the effects of the
      sodium channel activator,veratridine (2 x 10-6 M), on the CAl population spike
      amplitude (recorded in normal Krebs solution),indicating that the previously
      observed lack of effect of phenytoin on the NMDA receptor-mediated response was
      not due to impaired access of phenytoin to the biophase.6. These data support the
      conclusion that antagonism of NMDA receptor-mediated events is not a
      pharmacological property of phenytoin and that such an action is therefore
      unlikely to contribute to the anticonvulsant activity of this drug.

PMID- 7647986
TI  - Blockade by ONO-NT-012, a unique prostanoid analogue, of prostaglandin E2-induced
      allodynia in conscious mice.
AB  - 1. Intrathecal (i.t.) administration of prostaglandin E2 (PGE2) to conscious mice
      was reported to induce allodynia, a state of discomfort and pain evoked by
      innocuous tactile stimuli through prostaglandin E receptor subtype EP1 and
      hyperalgesia through prostaglandin E receptor subtypes EP2 and/or EP3. In the
      present study, we investigated the effects of an EP1 antagonist on these sensory
      disorders by use of ONO-NT-012 or AH6809. 2. ONO-NT-012 dose-dependently
      antagonized the PGE2-induced allodynia but had no effect on the PGE2-induced
      hyperalgesia by the hot plate test. On the other hand, AH6809 blocked the PGE2
      induced hyperalgesia at the highest dose examined (50 micrograms kg-1) but had no
      effect on the PGE2-induced allodynia. The i.t. injection of AH6809 or ONO-NT-012
      alone did not have any effect on the response to noxious or innocuous stimuli. 3.
      Increasing doses (5 pg kg(-1)-500 ng kg-1) of ONO-NT-012 produced parallel shifts
      to the right of the dose-response curves to PGE2. The Schild plot regression line
      was linear and the slope was close to unity. The pA2 value against PGE2 was
      calculated to be 9.96. 4. The present study demonstrates that i.t. administration
      of PGE2 exerts allodynia through EP1 in the mouse spinal cord and that ONO-NT-012
      is a highly potent, simple competitive antagonist for the PGE2-induced allodynia.

PMID- 7647987
TI  - Modulation of epidermal growth factor effects on epithelial ion transport by
      intestinal trefoil factor.
AB  - 1. The direct epithelial effects of epidermal growth factor (EGF) and its
      modulation by intestinal trefoil factor (ITF) have been studied in a human
      colonic adenocarcinoma cell line called Colony-29 (Col-29). 2. When grown in
      culture as confluent monolayers and voltage-clamped in Ussing chambers, these
      epithelia responded with an increase in short circuit current (SCC) to
      basolateral as well as to apically applied EGF although the latter responses (at
      10 nM) were only 25% of those observed following basolateral peptide. 3.
      Recombinant rat ITF (added to the basolateral surface) did not alter basal SCC
      levels, but it did enhance the electrogenic effects of basolateral EGF. The EC50
      values for EGF-induced ion transport were 0.25 nM in control, and 0.26 nM in ITF
      pretreated Col-29 epithelia. A significant increase in the size of EGF responses
      (0.1 nM-10 nM) was observed in the presence of 10 nM ITF and the half-maximal
      concentration for this modulatory effect of ITF was 7.6 nM. 4. The EGF-induced
      increases in SCC were partially inhibited (50%) by piretanide pretreatment,
      indicating that Cl- secretion is involved. EGF responses either in the presence
      or absence of ITF were also significantly reduced (84% and 66% respectively) by
      the cyclo-oxygenase inhibitor, piroxicam, therefore implicating prostaglandins as
      mediators of EGF-stimulated anion secretion. 5. We conclude that in confluent Col
      29 epithelia, basolateral EGF stimulates a predominantly prostaglandin-dependent
      increase in Cl- secretion that is enhanced by basolateral ITF, and that these two
      peptides may interact in normal and damaged mucosa to alter the local apical
      solute and fluid environment.

PMID- 7647988
TI  - Inhibitory actions of GABA on rabbit urinary bladder muscle strips: mediation by
      potassium channels.
AB  - 1. The actions of gamma-aminobutyric acid (GABA) upon rabbit urinary bladder
      muscle were investigated to determine whether they were mediated through
      potassium channels. 2. In vitro experiments were undertaken in which bladder
      muscle strips were caused to contract with carbachol. Addition of GABA or
      baclofen reduced the size of such evoked contractions in the case of GABA by 20.7
      +/- 3.2%, in the case of baclofen by 22.4 +/- 2.2%. 3. Electrical stimulation of
      autonomic nerves in bladder wall strips also evoked contractions which were
      significantly smaller in potassium-free Krebs solution. The size of contractions
      produced by carbachol on the other hand were unaffected by the absence of
      potassium in the Krebs solution. 4. The inhibitory actions of GABA and baclofen
      on carbachol-induced contractions of bladder muscle were detected at much lower
      concentrations in potassium-free compared with potassium containing solutions. 5.
      The inhibitory effects of baclofen were completely reversed by tetraethyl
      ammonium chloride between 1 and 5 mM, caesium chloride between 0.5 and 3 mM and
      barium chloride between 0.5 and 2.5 mM. The actions of baclofen were only
      partially reversed by 4-amino-pyridine between 1 and 5 mM. 6. It was concluded
      that the GABAB receptor-mediated inhibitory actions on rabbit urinary bladder
      smooth muscle cells were produced by activation of potassium channels.

PMID- 7647989
TI  - Effect of 5-hydroxytryptamine on the membrane potential of endothelial and smooth
      muscle cells in the pig coronary artery.
AB  - 1. Many endothelium-dependent vasodilators hyperpolarize the endothelial cells in
      blood vessels. It is not known whether these hyperpolarizations are linked to
      nitric oxide synthesis or to an endothelium-derived hyperpolarizing phenomenon,
      since most of the vasodilators release both factors. In this context, we first
      verified that the endothelium-dependent relaxations induced by 5
      hydroxytryptamine (5-HT) on pig coronary arteries are due only to the activation
      of the nitric oxide pathway. Then we studied the effects of 5-HT on membrane
      potential of endothelial and smooth muscle cells. 2. In the absence of
      endothelium, 5-HT caused a concentration-dependent contraction of coronary artery
      strips. No change of the smooth muscle cell membrane potential was observed
      during contraction to 1 microM 5-HT. 3. In the presence of 1 microM ketanserin to
      suppress the contractile effect of 5-HT, 5-HT induced concentration-dependent
      relaxation of endothelium-intact strips precontracted by 10 microM prostaglandin
      F2 alpha (PGF2 alpha). These relaxations were suppressed by 1 microM NG-nitro-L
      arginine, an inhibitor of nitric oxide synthesis, showing that they were produced
      predominantly by nitric oxide. 4. In the presence of 1 microM ketanserin, 1
      microM 5-HT did not change the smooth muscle cell membrane potential of strips
      precontracted by either 10 microM PGF2 alpha or by 10 microM acetylcholine (ACh).
      In the same conditions, 1 microM 5-HT caused a weak 2.6 +/- 0.4 mV
      hyperpolarization, of the endothelial cells. 5. In conclusion, the fact that 5-HT
      did not change the membrane potential of smooth muscle cells and only weakly
      hyperpolarized the endothelial cells during relaxations, suggests that in both
      cell types no electrical events accompany activation of the nitric oxide pathway.
      This is in contrast to the hyperpolarizations observed in endothelial and smooth
      muscle cells when the endothelium-derived hyperpolarization factor (EDHF) pathway
      is activated.

PMID- 7647991
TI  - Lipid metabolism.

PMID- 7647990
TI  - Proceedings of the British Pharmacological Society meeting. Sandwich, Kent, 5-7
      April 1995. Abstracts.

PMID- 7647992
TI  - Nutrition.

PMID- 7647994
TI  - Lipid metabolism.

PMID- 7647993
TI  - Genetics and molecular biology.

PMID- 7647995
TI  - Hyperlipidaemia and cardiovascular disease.

PMID- 7647996
TI  - Atherosclerosis: cell biology and lipoproteins.

PMID- 7647997
TI  - Therapy and clinical trials.

PMID- 7647998
TI  - Lipoprotein metabolism: more than the sum of its parts.

PMID- 7647999
TI  - Receptors for triglyceride-rich lipoproteins and their role in lipoprotein
      metabolism.
AB  - The triglyceride-rich lipoproteins in normal human plasma are VLDL and
      chylomicrons and their remnants. Several receptors for these lipoproteins have
      been described, most of them belonging to the LDL receptor family. The LDL
      receptor itself is able to recognize remnants through apolipoprotein E. However,
      the LDL receptor-related protein is the actual candidate to be the chylomicron
      remnant receptor in the liver and the VLDL receptor might be responsible for VLDL
      catabolism in muscle and adipose tissue.

PMID- 7648000
TI  - Postprandial lipoprotein metabolism and atherosclerosis.
AB  - The metabolism of chylomicrons and their remnants is a highly facilitated route
      to distribute energy from the diet for storage in adipose tissue or immediate use
      in the muscles. It has been proposed that chylomicron remnants are atherogenic,
      and a delayed clearance of chylomicron remnants seems to be associated with
      compositional abnormalities of other cholesterol-rich lipoproteins. Furthermore,
      the plasma concentration of chylomicron remnants is very low compared with all
      other major lipoprotein species. These arguments suggest that the metabolism of
      chylomicrons may not be directly implicated in atherogenesis, but it may instead
      enhance the atherogenicity of endogenous lipoproteins. This review critically
      examines the current literature in this field.

PMID- 7648001
TI  - Lipases and lecithin: cholesterol acyltransferase in the control of lipoprotein
      metabolism.
AB  - Lipoprotein lipase, hepatic lipase, and lecithin: cholesterol acyltransferase
      have coordinated enzymatic roles in lipoprotein metabolism. New evidence suggests
      that the lipases are multifunctional proteins that are able to mediate
      lipoprotein binding and uptake. The importance of all three enzymes in the
      control of lipoprotein metabolism can be explored in the future by using the
      newly generated transgenic animals.

PMID- 7648002
TI  - Structure and metabolism of lipoprotein (a).
AB  - An understanding of the complex structural and metabolic features of lipoprotein
      (a) is essential because this lipoprotein particle, with poorly recognized
      physiological functions, has been implicated in both thrombogenesis and
      atherogenesis. Studies aimed at investigating the structure-function relationship
      of apolipoprotein (a) have generated new useful information. In-vivo and in-vitro
      studies have provided insights into the synthesis, secretion, and association of
      apolipoprotein (a) with apolipoprotein B100 and the mechanisms regulating the
      lipoprotein (a) concentration in the bloodstream.

PMID- 7648003
TI  - Cell membrane structure and lipoprotein metabolism.
AB  - Knowledge of the effect of the plasma membrane structure on lipoprotein
      metabolism is relatively limited. Receptor activity and, thereby, the endocytic
      pathway of lipoprotein particle catabolism is reported to be affected. The
      reverse cholesterol transport pathway is clearly affected because altered rates
      of cholesterol efflux from different cellular plasma membranes have been
      observed. Changes in the structure and lipid organization of the membranes in
      arterial wall cells can also alter vessel relaxation.

PMID- 7648004
TI  - Insulin resistance and lipoprotein metabolism.
AB  - Dyslipidaemia in insulin resistance comprises elevated plasma triglycerides,
      decreased HDL, a preponderance of small, dense LDL and increased postprandial
      lipaemia. In terms of cause and effect, small, dense LDL, alimentary
      hyperlipidaemia and changes in HDL are consequences of elevated triglycerides.
      These abnormalities can become frequent if triglycerides exceed a threshold value
      of approximately 1.5 mmol/l. Therefore, it is mandatory to maintain plasma
      triglycerides as low as possible in noninsulin-dependent diabetic and insulin
      resistant individuals to prevent the potentially atherogenic and metabolic
      consequences of hypertriglyceridaemia.

PMID- 7648005
TI  - Sex hormones, lipoproteins, and vascular reactivity.
AB  - The HDL-raising effect of estrogen replacement is mediated by an increase in HDL
      apolipoprotein A-I production and not by a decrease in the clearance rate. Large
      scale clinical trials have shown that medroxyprogesterone acetate removes most of
      the HDL-raising effects of concomitant estrogen treatment. Testosterone decreases
      HDL levels in both men and women. Lipoprotein (a) levels are reduced by estrogen
      replacement, but are not affected by medroxyprogesterone. The acute systemic
      administration of estrogen to postmenopausal women improves the endothelium
      dependent vasodilation of coronary arteries and forearm resistance vessels. Usual
      doses of oral estrogen replacement therapy improve the endothelium-dependent and
      endothelium-independent vasodilator responses in the forearm in women who have
      risk factors for atherosclerosis. These effects may be mediated by an antioxidant
      action of estrogen.

PMID- 7648006
TI  - Impact of n-3 fatty acids on lipoprotein metabolism.
AB  - The n-3 fish oils initially attracted the attention of the research community
      because of their protective actions against coronary artery disease. However,
      since then, research in this field has contributed to the basic understanding of
      several aspects of lipid and lipoprotein metabolism.

PMID- 7648007
TI  - Methods for measurement of fatty acid and cholesterol metabolism.
AB  - The measurement of dynamic fluxes of lipids (biosynthesis, oxidation, and
      intermediary metabolism) poses difficult challenges. Two fundamental advances
      have been made recently for measuring the biosynthesis of lipids, namely mass
      isotopomer distribution analysis and labeled water incorporation. These
      techniques have resolved the central methodologic problem in biosynthesis by
      establishing the true precursor isotope enrichment. Mass isotopomer distribution
      analysis also permits uncontaminated pulse-chase decay curves and intracellular
      precursor fluxes to be measured. In contrast, the isotopic measurement of lipid
      oxidation rates remains unreliable because of the wide variability in the
      recovery of labeled carbon dioxide.

PMID- 7648009
TI  - Modeling magnetization transfer for biological-like systems using a semi-solid
      pool with a super-Lorentzian lineshape and dipolar reservoir.
AB  - Magnetization transfer is modeled as an exchange between a liquid pool and a semi
      solid pool where the semi-solid pool has, in addition to the Zeeman reservoir, a
      dipolar reservoir. The lineshape for the liquid pool is characterized by the
      usual Lorentzian, whereas the semi-solid pool is characterized as a super
      Lorentzian. Three systems were investigated: (1) a membrane mixture of a
      phosphatidylcholine lipid (POPC) and cholesterol; (2) lyophilized white matter at
      eight solid concentrations ranging from 1 to 24%; and (3) fresh white matter. In
      all systems, this model fitted the experimental data well with the effect of the
      dipolar reservoir being most important for the membrane mixture. For the tissue,
      the dipolar reservoir is not required and the two-pool model with a single Zeeman
      reservoir for the semi-solid spins characterizes the experimental data equally
      well.

PMID- 7648010
TI  - Design and analysis of microcoils for NMR microscopy.
AB  - The signal-to-noise ratio achieved in a nuclear magnetic-resonance microscopy
      experiment is directly related to the performance of the radiofrequency coil. An
      accurate determination of coil performance requires that the resistance of the
      coil be well characterized. Traditional high-frequency electric-circuit models
      used to describe larger NMR coils are inadequate when the diameter of the
      conductor is reduced to the dimensions of the electrical skin depth (delta) at
      the frequency of operation. A more extensive model based on a scaling parameter
      that includes delta is presented. This model complements other existing circuit
      models that represent sample losses, ground-loop and parasitic losses, and the
      signal induced in the RF coil. Experimental verification is accomplished using a
      series of solenoidal microcoils in 1H NMR microspectroscopy experiments at 4.7 T
      (200 MHz). This study demonstrates for the first time that a predictable
      performance enhancement is achieved using microcoils as small as 50 microns in
      diameter.

PMID- 7648008
TI  - New in-vivo techniques for measuring lipoprotein metabolism.
AB  - Stable, nonradioactive tracer techniques have provided a safe means of studying
      in-vivo lipoprotein metabolism, and endogenous labelling with amino acids has
      allowed apolipoprotein synthesis to be analysed directly. Recent studies have
      dealt with experimental design, mass spectrometry techniques and the validity of
      simple formulae used to derive primary kinetic data. Concerns that stable
      isotopes give different results to the traditional radiolabelling studies have
      been allayed, in the case of apolipoprotein A-I, by published work. Studies
      conducted during the review period have also examined the mechanisms responsible
      for the low plasma concentrations of apolipoprotein A-I and apolipoprotein A-II
      in lecithin:cholesterol acyltransferase deficiency and the increased
      concentrations of HDL-apolipoprotein A-I caused by transdermal oestrogen hormone
      replacement therapy. The first analysis of lipoprotein-lipid rather than
      lipoprotein-apolipoprotein metabolism using stable isotopes has also been
      reported.

PMID- 7648011
TI  - The conformation of the monensin-A-sodium complex in solution determined from
      self-consistent NOE distance constraints.
AB  - The structure of the monensin-A-sodium complex in solution in chloroform is
      determined by means of NOESY experiments and distance-geometry calculations. The
      information extracted from the NOESY spectra is maximized by estimating errors on
      cross-peak intensities (D.L. Turner, J. Magn. Reson. A 107, 239 (1994)) which are
      used in defining upper and lower distance constraints and also for weighting when
      calculating distance scaling factors. The resulting structure is closely similar
      to that found in the crystal, with deviations which fall within the range found
      for different crystal forms.

PMID- 7648012
TI  - 15N, 13C, and 1H NMR assignments and secondary structure for T4-lysozyme.
AB  - Sequence-specific 1H, 13C, and 15N backbone assignments and 1H and 13C side-chain
      assignments have been identified for T4-lysozyme (164 residues, MW = 18.7 kDa). A
      variety of double- and triple-resonance 3D techniques were used. Some of these
      methods were applied in unconventional ways and a detailed description of the
      advantages and disadvantages of these approaches is given. Complete backbone
      resonances for 162 of the 164 residues and partial assignments for the remaining
      2 residues were obtained. The 1H and 15N assignments are in agreement with those
      obtained previously by McIntosh et al. who used selective labeling (L.P. McIntosh
      et al., Biochemistry 29, 6341 (1990)). Complete proton and carbon side-chain
      assignments were made for 120 residues and partial side-chain assignments were
      made for 42 additional residues. A qualitative analysis of the medium-range NOESY
      data reveals a secondary structure consistent with the X-ray crystallographic
      structure.

PMID- 7648014
TI  - Detection of an extracellular contribution from a second-rank tensor to the
      double-quantum-filtered 23Na NMR spectrum in the isolated perfused rat heart.

PMID- 7648013
TI  - 19F-[1H] nuclear Overhauser effect and proton decoupling of 5-fluorouracil and
      alpha-fluoro-beta-alanine.
AB  - 19F-[1H] magnetic double-resonance experiments were performed on model solutions
      of the antitumor drug 5-fluorouracil (5-FU) and of alpha-fluoro-beta-alanine
      (FBAL) in order to improve 19F NMR sensitivity for the application in
      pharmacokinetic studies in vivo. Upon driving the proton spins into saturation, a
      fluorine signal enhancement (nuclear Overhauser effect) was observed on the order
      of the theoretical NOE maximum gamma H/2 gamma F = 53% for purely dipolar coupled
      19F-1H spin systems in extreme narrowing. The dependence of the effect on proton
      excitation frequency and temporal parameters was measured and cross-relaxation
      rate constants of 0.07 s-1 (5-FU) and 0.19 s-1 (FBAL) were determined.
      Irradiation of the proton spin system by a broad pulse during the 19F signal
      detection period removed FBAL multiplet splittings completely and narrowed the
      linewidth of this resonance band by a factor of six. Application of proton
      presaturation in the 19F NMR examination of a patient undergoing 5-FU
      chemotherapy enhanced the signal-to-noise ratio of the major 5-FU catabolite FBAL
      detected noninvasively in the liver.

PMID- 7648015
TI  - Carbon relaxation in randomly fractionally 13C-enriched proteins.

PMID- 7648016
TI  - J-coupling restraint potentials for nonstereospecifically assigned methylene
      protons and ensemble-average calculations.

PMID- 7648017
TI  - Measuring the 13C NMR shielding tensor of 13CO bonded to haemoglobin.

PMID- 7648018
TI  - Solution conformations and dynamics of arginine side chains in a protein deduced
      from three-bond 15N-1H coupling constants.

PMID- 7648019
TI  - Structure determination from NOESY intensities using a metropolis simulated
      annealing (MSA) refinement of dihedral angles.

PMID- 7648020
TI  - Comparative pathology of microcystin-LR in cultured hepatocytes, fibroblasts, and
      renal epithelial cells.
AB  - The cyanobacterial toxin microcystin-LR (MCLR) is a potent inhibitor of protein
      phosphatases 1 and 2A, and is selectively toxic to the liver in vivo and to
      isolated hepatocytes in vitro. This selectivity is believed to be due to toxin
      uptake via bile acid carriers. We investigated at the light and ultrastructural
      levels the effects of high concentrations of MCLR and long incubation times to
      determine in vitro whether fibroblasts and kidney cells (non-target cells)
      respond in the same manner as do hepatocytes (target cells) at low concentrations
      and short incubation times. Cultured rat skin fibroblasts (ATCC 1213) and rat
      kidney epithelial cells (ATCC 1571) were incubated with with MCLR at 133 microM
      for 1-24 hr. Lesions in these cells were compared with those in cultured
      hepatocytes incubated MCLR at 13.3 microM from 1 to 32 min. Lesions in
      hepatocytes, kidney cells, and fibroblasts were noted at 4 min, 1 hr, and 8 hr,
      respectively, after initial exposure to MCLR. Lesions in all three cell types
      progressed and included plasma membrane blebbing, loss of cell-to-cell contact,
      clumping and rounding of cells, cytoplasmic vacuolization, and redistribution of
      cytoplasmic organelles. Loss of microvilli, whorling of rough endoplasmic
      reticulum, dense staining and dilated cristae in mitochondria, and pinching off
      of membrane blebs were noted only in hepatocytes. Nuclear changes typical of
      apoptosis were observed only in fibroblasts and kidney cells. Similarities in
      responses of different cell types to MCLR exposure probably reflect a common
      biochemical mechanism of action, i.e., inhibition of protein phosphatases 1 and
      2A as described by others.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7648021
TI  - Induction of apoptosis by T-2 toxin and other natural toxins in HL-60 human
      promyelotic leukemia cells.
AB  - Based on the DNA fragmentation profile in gel electrophoresis and the
      morphological changes in electron microscopy, the induction of apoptotic nuclear
      changes by mycotoxins and other microbial products, in total 31 chemicals, was
      investigated in HL-60 human promyelotic leukemia cells, along with the
      cytotoxicity tests with 3-[4,5-dimethylthiazol-zyl]-2,5-diphenyltetrazolium
      bromide (MTT) and trypan blue exclusion. Among the chemicals tested,
      trichothecenes (T-2 toxin, roridin A, nivalenol, deoxynivalenol), certain
      anthraquinones (luteoskyrin, skyrin, 2-hydroxyemodin), diketopiperazines
      (emethallicin A, emestrin), isocoumarins (ochratoxin A, citrinin), lactone
      (penicillic acid), dihydrobisfuran (aflatoxin B1), potassium ionophore
      (valinomycin), and an inhibitor of interleukin-2 synthesis (cyclosporin A) were
      positive for the induction of DNA fragmentation. No DNA fragmentation was
      observed under the present conditions with fumonisin B1, cyclic peptides
      (cyclochlorotine, phalloidin, microcystin-LR), certain anthraquinones (emodin,
      chrysophanol, rugulosin), and others (sterigmatocystin, cytochalasin A,
      griseofulvin, fusaric acid, kojic acid, rubratoxin B, butenolide, wortmannin,
      FK506, and sphingosine). The apoptotic changes in the cells exposed to T-2 toxin
      and luteoskyrin were confirmed by electron microscopic observation. Detailed
      experiments on dose and time dependencies revealed that T-2 toxin induced the
      apoptosis at 10 ng/ml (= 4 x 10(-8) M) levels within 2-6 hr without significant
      cytotoxicity evaluated by the dye exclusion and MTT.

PMID- 7648022
TI  - Metabolism of the Fusarium mycotoxins zearalenone and deoxynivalenol by yeast
      strains of technological relevance.
AB  - The Fusarium mycotoxin zearalenone (ZEA), added at a level of 2 micrograms/ml,
      was reduced stereoselectively by cultures of Candida tropicalis, Torulaspora
      delbruckii, Zygosaccharomyces rouxii, and 7 Saccharomyces strains to both alpha-
      and beta-zearalenol. In contrast, only alpha-zearalenol was produced from ZEA by
      Pichia fermentans and several yeast strains of the genera Candida, Hansenula,
      Brettanomyces, Schizosaccharomyces, and Saccharomycopsis. No glucose conjugates
      of ZEA (zearalenone-4-beta-D-glucopyranoside) were detected. The trichothecene
      mycotoxin deoxynivalenol (DON) was not metabolized by any of the yeast strains
      that were used for analysis.

PMID- 7648023
TI  - Fate of a single dose of 14C-labelled fumonisin B1 in vervet monkeys.
AB  - The mycotoxin fumonisin B1 (FB1) was dosed as 14C-labelled FB1, to male vervet
      monkeys (Cercopithecus aethiops) both by intravenous (i.v.) injection (2 monkeys,
      dose 1.72 mg [86 kBq]/kg body weight) and by gavage (2 monkeys, dose 6.42 mg [321
      kBq]/kg body weight). Excreta were collected over a 24-hr period, whereafter the
      monkeys were sacrificed and selected organs and contents of the gut collected to
      determine the distribution of the 14C-label. The bulk of the radioactivity
      recovered from tissue was found in the liver (mean of 1.92% in i.v.-dosed
      monkeys; 0.64% in gavage-dosed monkeys). Of the other organs analysed, the
      following mean amounts of radioactivity were recovered in organs of i.v.- and
      gavage-dosed monkeys, respectively: muscle, 0.62% and 0.14%; kidney, 0.37% and
      0.03%; brain, 0.08% and 0.02%; lung, 0.07% and 0.03%; heart, 0.04% and 0.01%;
      spleen, 0.02% and < 0.01%; plasma, 0.66% and 0.12%; red blood cells, 0.11% and
      0.01%; while a further 68.1% and 64.0% were recovered in excreta, bile, and the
      gut contents. Analysis of faeces and gut contents showed that radioactivity was
      due to FB1, its partially hydrolysed metabolites, and trace amounts of the fully
      hydrolysed aminopentol moiety. Analysis of bile showed an absence of hydrolysis
      products, indicating that hydrolysis occurred only in the gut, resulting in the
      removal of the tricarballylic acid moiety at the C14-position. Determination of
      FB1, levels in plasma following a gavage dose indicated that only limited amounts
      of FB1 were absorbed, as plasma levels peaked after 1-2 hr with levels below 210
      ng/ml.

PMID- 7648024
TI  - Biological activity of cyclopaldic acid, a major toxin of Seiridium cupressi, its
      six derivatives, and iso-cyclopaldic acid.
AB  - Cyclopaldic acid (CA), its six derivatives, and iso-cyclopaldic acid (IsoCA) were
      assayed for toxicity to cuttings of three species of cypress, as well as to mung
      bean, oat, and tomato explants. Toxicity to host and non-host plants of CA
      derivatives having one or both of the aldehyde groups transformed was less than
      that of CA. Shoot tissues of Cupressus macrocarpa artificially infected by
      Seiridium cupressi leached electrolytes more than those of C. sempervirens and C.
      arizonica. CA, IsoCA, and to a lesser extent the monoacetylated, phenylhydrazone
      and hydrogenated derivatives of CA caused loss of electrolytes from cypress
      tissues. CA, IsoCA, and monoacetyl CA caused limited callus development of
      cypress tissues. Diacetylhydrazone CA enhanced the yield of cypress callus
      tissue. CA derivatives having both aldehyde groups modified induced root
      formation on cypress cuttings. The antifungal activity showed by CA toward
      species of Botrytis, Fusarium, and Geotrichum markedly decreased in its
      derivatives. The inhibitory effect of CA on esterases was exhibited also by IsoCA
      and the monoacetylated derivative.

PMID- 7648025
TI  - Studies on structure-activity relationship of seiridins, phytotoxins, produced by
      three species of Seiridium.
AB  - The phytotoxins seiridin (SEI) and iso-seiridin (ISE), two delta alpha,beta
      butenolides produced in vitro by Seiridium cardinale, S. cupressi, and S.
      unicorne, as well as their derivatives obtained by chemical modification of each
      toxin, were analyzed for their bioactivity. The effects each compound on host and
      non-host plants and their antimicrobial activity on bacteria were investigated.
      The toxicity of both seiridins (SEIs) decreased in the derivatives with
      modifications of the gamma-lactone ring or with acetylation of the hydroxy group
      of the aliphatic side chain at C-4. Shoot tissues of Cupressus macrocarpa
      artificially infected by S. cardinale leached electrolytes more than those of C.
      sempervirens and C. arizonica. Electrolyte loss from shoot tissues of cypress
      plants treated with each derivative also decreased for most of them. Seed
      germination was not affected by SEI and ISE derivatives. Inhibition of root
      growth of three herbaceous test plants was studied. SEI and 3,4-dihydro SEI were
      active to germlings of lettuce. No ISE derivative affected root growth of lettuce
      and oat germlings. Reduction was observed on roots of radish germlings treated
      with acetyl ISE or 3,4-dihydro ISE. No derivative of SEI or ISE elicited hormone
      like activity as SEI did. Antibacterial activity shown by SEI and ISE at 150
      microM accounted for both hydrogenated derivatives of SEI. The integrity of the
      delta alpha,beta-unsaturated-gamma-lactone ring and the location of the hydroxy
      group in the heptyl side chain are features of importance in biological activity
      of the two butenolides.

PMID- 7648026
TI  - Isolation and identification of two potent neurotoxins, aspartic acid and
      glutamic acid, from yellow star thistle (Centaurea solstitialis).
AB  - Horses grazing for prolonged periods on yellow star thistle (YST), a plant which
      grows wild in western parts of the United States, develop an extrapyramidal
      disorder known as nigropallidal encephalomalacia (NPE). Attempts have been made
      to identify, isolate, and characterize the toxins responsible for the disease in
      animals. Using the organotypic tissue culture system on mouse cortical explants
      as a specific assay method for neurotoxicological evaluation, it has been
      possible to isolate and characterize two potent neuroexcitotoxic compounds,
      aspartic and glutamic acids, the former being the major toxic component in the
      alcoholic extract of the plant. There is also evidence that other neurotoxic
      compounds are present in the extract. The detailed procedure for isolation and
      characterization of these compounds is given here.

PMID- 7648027
TI  - Models to study enteropathogenic bacteria: lessons learned from Shigella.

PMID- 7648028
TI  - The potential of ribozymes as antiviral agents.
AB  - Ribozymes are promising tools for the specific inhibition of viral gene
      expression and replication. They represent one of the most attractive
      developments of antisense nucleic acids, which have been shown in the past few
      years to act as antiviral agents. Ribozymes not only complex with target
      sequences via complementary antisense sequences, but also hydrolyze the target
      site.

PMID- 7648029
TI  - The epidemiology of HIV infection and AIDS in Africa.
AB  - Only 10 years after it was first recognized in Africa, HIV infection is already
      the leading cause of adult death in many cities of the continent and has
      increased childhood mortality. This article reviews critical aspects of the
      dynamics of this epidemic, including routes of transmission, factors influencing
      the rate of transmission and strategies to combat this disaster.

PMID- 7648030
TI  - Moving through the membrane with filamentous phages.
AB  - Filamentous phages are small, highly evolved parasites that can reproduce and
      disseminate without killing their host. During assembly, virion proteins are
      transferred from the host membrane to the single-stranded DNA phase genome and
      simultaneously secreted from the cell. Filamentous phage assembly shares certain
      features with bacterial processes responsible for the assembly of cell-surface
      structures and for extracellular protein secretion.

PMID- 7648031
TI  - Unconstrained bacterial promiscuity: the Tn916-Tn1545 family of conjugative
      transposons.
AB  - Conjugative transposons are highly ubiquitous elements found throughout the
      bacterial world. Members of the Tn916-Tn1545 family carry the widely disseminated
      tetracycline-resistance determinant Tet M, as well as additional resistance
      genes. They have been found naturally in, or been introduced into, over 50
      different species and 24 genera of bacteria. Recent investigations have led to
      insights into the molecular basis of movement of these interesting mobile
      elements.

PMID- 7648032
TI  - A TH1-TH2-like switch in candidiasis: new perspectives for therapy.
AB  - An imbalance in TH1-type and TH2-type responses may allow Candida albicans to
      modify the host response to favor its own persistence. This hypothesis has
      important consequences for allergy, autoimmunity and co-infection, and also
      highlights a potential role for cytokine and anti-cytokine therapy in Candida
      related pathology.

PMID- 7648033
TI  - Collectins and viral infection.
AB  - Members of the collectin protein family are beta-inhibitors of influenza virus
      infectivity. They bind to carbohydrate on the surface of influenza virus and
      sterically inhibit virus interaction with host cells, and may also act as
      opsonins. We propose that collectins, by interacting with glycosylated viruses,
      act as innate inhibitors of viral infection.

PMID- 7648035
TI  - [Vitamins B and alpha-lipoprotein acid in the therapy of polyneuropathies. Report
      from the media workshop Polyneuropathies: Clinical Picture and Therapeutic Needs.
      Heidelberg, 1994].

PMID- 7648034
TI  - Herpes simplex virus vaccines as immunotherapeutic agents.
AB  - As persistent viruses can escape immune surveillance, chronic or recurrent
      disease can be a major problem. Only after nearly 60 years of work have recent
      reproducible data, using herpes simplex virus infection as a model for persistent
      viral disease, established that vaccine immunotherapy is effective in the
      treatment of such viral infections.

PMID- 7648036
TI  - Hereditary disease as a cause of childhood blindness: regional variation. Results
      of blind school studies undertaken in countries of Latin America, Asia and
      Africa.
AB  - There is evidence from developed countries that genetic disease is the major
      cause of childhood blindness. Little data are available from most developing and
      newly industrialised countries concerning the relative importance of hereditary
      diseases as a cause of childhood blindness. Children in schools for the blind in
      13 countries of Africa, Latin America and Asia were examined between 1990 and
      1994 using a standardised method The anatomical site of abnormality and
      underlying aetiology were analysed for children with a corrected acuity in the
      better eye of less than 6/60 (severe visual impairment and blindness, svi/BL). In
      these countries II-39% of svi/BL was attributed to genetic disease. Genetic
      diseases were responsible for a higher proportion of childhood visual loss in
      countries with higher levels of socio-economic development. An autosomal
      recessive mode of inheritance was reported in 22-52% of children with genetic
      disease. Retinal dystrophies were the commonest form of genetic eye disease (49
      80%) in all countries apart from Thailand and the Philippines where cataract was
      the commonest (43.9%). The role of consanguinity, and opportunities for further
      research are discussed.

PMID- 7648037
TI  - Unusual association of juvenile macular dystrophy with congenital hypotrichosis:
      occurrence in two siblings suggesting autosomal recessive inheritance.
AB  - A familial association between juvenile macular dystrophy and congenital
      hypotrichosis is described in two siblings aged 25 and 23 years. We put forward
      arguments for locating the retinal alteration at the level of the retinal pigment
      epithelium and suggest that the hair disorder could be a Marie-Unna type
      hypotrichosis. This association is transmitted as an autosomal recessive
      condition.

PMID- 7648038
TI  - Familial pars planitis.
AB  - Pars planitis is an intraocular inflammatory disorder which usually affects
      children or young adults and is characterized by vitreous cells and debris
      ('snowballs'), exudate, and 'snowbank' formation along the pars plana, variable
      periphlebitis, and cystoid macular edema. Although no inheritance pattern has
      been defined, familial cases of pars planitis have been reported. This report
      describes pars planitis in two sisters, one of whom had evidence of demyelinating
      disease at presentation. The literature on familial pars planitis is reviewed. To
      the author's knowledge this is the first case of familial pars planitis as the
      presenting sign of possible demyelinating disease.

PMID- 7648039
TI  - Richner-Hanhart syndrome (tyrosinemia type II). Case report and literature
      review.
AB  - Richner-Hanhart syndrome (Tyrosinemia Type II) is an autosomal recessive disorder
      of amino acid metabolism characterized by ocular changes, painful palmoplantar
      hyperkeratosis, and mental retardation. Serum tyrosine increases due to tyrosine
      aminotransferase deficiency resulting in the deposition of tyrosine crystals in
      the cornea and in corneal inflammation. Patients are often misdiagnosed as having
      herpes simplex keratitis. We report on a child who presented with bilateral
      keratitis secondary to Tyrosinemia Type II diagnosed as herpes simplex keratitis.

PMID- 7648040
TI  - Photoaversion in Leber's congenital amaurosis.
AB  - Photoaversion is a prominent symptom of a number of infantile genetic ocular
      disorder such as congenital glaucoma, aniridia, albinism, and cone dystrophies
      including achromatopsia. Photoaversion has not been widely recognized as a
      clinical feature of Leber's congenital amaurosis. We present two patients who
      were diagnosed clinically with achromatopsia because of nystagmus, absent color
      vision, reduced visual acuity, and moderately severe photoaversion in the absence
      of anterior segment abnormalities. The photopic and scotopic responses of the
      electroretinogram (E R G) were nonrecordable in both patients indicating
      involvement of both cone and rod systems. The diagnosis was then revised to one
      of Leber's congenital amaurosis. Photoaversion can be a prominent clinical
      feature in some patients with Leber's congenital amaurosis. The E R G clinches
      the diagnosis. These patients may constitute a distinct genetic subtype of the
      disease and molecular genetic studies will help resolve this issue.

PMID- 7648041
TI  - Fracture of polyurethane double pigtail stents: an in vivo retrospective and
      prospective fluoroscopic study.
AB  - OBJECTIVE: To study the behaviour of pigtail polyurethane ureteric stents during
      breathing and change in body habitus and thereby explain some side-effects of
      stenting, particularly spontaneous stent fracture. PATIENTS AND METHODS: The
      study comprised retrospective evaluation of records and radiographs of seven
      patients (five men and two women, mean age 41; SD 10.9 years) who were admitted
      with fractured polyurethane pigtail stents, and a prospective fluoroscopic study
      of the behaviour of 14 stents in 12 patients (11 men and one woman; mean age 40;
      SD 9.3 years) during breathing, spinal flexion, extension and rotation. RESULTS:
      Five of the seven pigtail stents fractured where the stent crossed the lateral
      edge of psoas muscle, 7-10 cm below the renal coil of the stent. The sixth stent
      was fractured at its lower third and the seventh fractured just proximal to the
      stent's bladder coil. The prospective study revealed a 20-80 degrees bend in the
      upper third of 11 of the 14 stents and a 35 degrees bend in the lower third of
      two stents. A 1-5 cm craniocaudal movement and a 0-2 cm vertical movement of the
      stents occurred during breathing and spinal flexion and extension. There were no
      changes in stent configuration during spinal lateral rotation or at the sacral
      promontary. The bend in the upper third of the ureter was profound in two stents
      whose vertical movement was restricted by other conditions. CONCLUSION: As the
      kidney-to-bladder distance shortens during inspiration and spinal flexion, the
      stent adapts by bending and/or moving. Fracture of the stent may be caused by
      repeated mechanical stress, particularly across the side-holes, and by diminution
      of its tensile strength by depolymerization during long indwelling times. Large
      polyurethane stents tended to bow, displacing the upper ureter anteriorly, while
      small, soft stents conformed to the anatomical course of the ureter, suggesting
      that they should be used after open or endoscopic surgery to the upper two-thirds
      of the ureter. Stress on the stent can be minimized by choosing the correct
      length, particularly where vertical stent movement is limited by other
      conditions.

PMID- 7648043
TI  - The rosebud technique for creation of a neomeatus after partial or total
      penectomy.

PMID- 7648042
TI  - Ex vivo activated memory T-lymphocytes as adoptive cellular therapy of human
      renal cell tumour targets with potentiation by cis-diamminedichloroplatinum(II).
AB  - OBJECTIVE: To determine if cis-diamminedichloroplatinum(II) (CDDP) enhances, by
      immunomodulation, ex vivo anti-tumour cytotoxicity of autolymphocyte therapy
      (ALT) against a chemotherapy-resistant tumour, and if lysis is mediated through T
      cells, NK-cells, or both. MATERIALS AND METHODS: Human renal cell carcinoma (RCC)
      target cells were derived from surgical specimens and incubated in complete
      medium (CM) with CDDP, or in CM alone (control group). ALT-cells were prepared
      from autologous whole peripheral blood mononuclear cells (PBMC) or NK-cell (CD56)
      depleted PBMC obtained before surgery. Tumour cells from each group were labelled
      with chromium-51(51Cr) and used as targets for ALT-cells and PBMC in a standard
      (4 h) and delayed (18 h) 51Cr-release assay at varying effector/target ratios
      (E:T). RESULTS: Tumour cells incubated in CDDP showed enhanced lysis, as measured
      by the 51Cr-release assay, at all E:T tested. This lysis was significantly
      greater during the 18 h assay and when ALT-cells were used as the effector cells
      rather than PBMC. Depletion of CD45RO+ (memory) T-cells from the ALT cell
      population precluded both the 4 and 18 h tumour cell lysis. Depletion of NK-cells
      (CD56+) diminished the ex vivo lysis of autologous targets during the 4 but not
      the 18 h assay. ALT-cells derived from two patients demonstrated ex vivo tumour
      specificity against autologous and allogeneic RCC. CONCLUSIONS: These data
      suggest that: (i) ex vivo activated memory T-cells are the principal component
      demonstrating significant tumour-specific cytotoxicity of ALT-cells against RCC
      tumour targets; (ii) CDDP may alter the physical properties of tumour cells
      rendering them susceptible to immune-mediated attack; (iii) the combination of
      ALT and CDDP may lead to increased therapeutic efficacy in patients with
      metastatic RCC.

PMID- 7648044
TI  - Operative retroperitoneoscopy.

PMID- 7648045
TI  - Breast lump--an unusual presentation of renal cell carcinoma.

PMID- 7648046
TI  - Eosinophilic cystitis-induced severe urethral stricture.

PMID- 7648047
TI  - Congenital urological anomalies in Sotos syndrome.

PMID- 7648048
TI  - Laparoscopic excision of the sinusoidal remnants of the urachus in a 3-year-old
      boy.

PMID- 7648049
TI  - Omental herniation through a small laparoscopic port.

PMID- 7648050
TI  - An unusual cause of iatrogenic bladder stone.

PMID- 7648051
TI  - Stone formation on permanent suture material used previously in colposuspension.

PMID- 7648052
TI  - Laparoscopic hemi-nephrectomy in a horseshoe kidney.

PMID- 7648053
TI  - Cysts of seminal vesicles presenting as intra-abdominal swellings.

PMID- 7648054
TI  - Extraction of an intravesical thermometer using a flexible cystoscope.

PMID- 7648055
TI  - Management of Foley catheters in women--a new technique.

PMID- 7648056
TI  - Phimosis or congenital megaprepuce.

PMID- 7648058
TI  - Prevention of urethral stricture recurrence using clean intermittent self
      catheterization.

PMID- 7648057
TI  - Choosing the correct pain relief for extracorporeal lithotripsy.

PMID- 7648059
TI  - Maximum and average urine flow rates in normal children--the Miskolc nomograms.
AB  - OBJECTIVE: To establish normal reference ranges of urinary flow rates in
      children. SUBJECTS AND METHODS: From a screening programme, 200 healthy children
      (96 girls and 104 boys, between 3 and 18 years old) with no renal, urological,
      psychological or neurological disorders were selected, and they provided 433
      micturitions for analysis. The children were divided into those with body surface
      areas of < 0.92 m2, between 0.92 and 1.42 m2 and > 1.42 m2. The voided volume,
      maximum and average flow rates of urine were measured. Data were fitted by
      several mathematical functions and goodness-of-fit determined. RESULTS: The
      relationship between maximal or average flow rates and voided volume was best
      fitted by a logarithmic function. The maximal and average urine flow rate
      nomograms are given in centile form for each body surface area group in both
      girls and boys. Flow rates showed a close relationship with voided volumes in
      both sexes and for all body sizes. The average maximal and average flow rates
      were higher in girls than in boys. CONCLUSION: Normal nomograms of maximal and
      average urine flow rates of girls and boys at three different body surfaces are
      presented in centile form. These may be useful for diagnosing lower urinary tract
      disturbances in children over a wide range of body size and voided volumes.

PMID- 7648060
TI  - Broadening the concept of urinary tract infection.

PMID- 7648061
TI  - Antegrade scrotal sclerotherapy for the treatment of varicocele in childhood and
      adolescence.
AB  - OBJECTIVE: To test the efficacy of antegrade scrotal sclerotherapy (ASS) for the
      treatment of varicocele in teenagers. PATIENTS AND METHODS: The study included 38
      patients (mean age 14.9 years, range 12-18) with left-sided varicocele. Three
      patients had a grade 1 varicocele, 22 were grade 2 and 13 were grade 3. ASS was
      performed under local anaesthesia on an out-patient basis. RESULTS: ASS was
      accepted by all patients except one. There were no peri-operative problems and
      only one patient developed post-operative epididymitis. During 9 to 15 months of
      follow-up (mean 11 months), only two patients developed persistence of a lower
      grade of varicocele. CONCLUSION: This study illustrates that ASS is a safe and
      successful out-patient procedure for the treatment of varicocele in teenagers.

PMID- 7648062
TI  - High educational level associated with reduced semen quality in men with
      asymptomatic varicocele testis.
AB  - OBJECTIVE: To investigate the relationship between education, intelligence,
      varicocele testis and semen quality. SUBJECTS AND METHODS: Of 542 newly-enlisted
      soldiers (median age 20 years, range 20-24) 47 men were found who had varicocele
      testis. Semen quality was assessed in 39 of the men with a varicocele and
      compared with a similar group with no varicocele. The educational level and
      intelligence of both groups was also assessed and compared. RESULTS: There was a
      significantly reduced quality of semen in men with varicoceles and in men with >
      10 years of school education. There was no significant relationship between
      intelligence level and semen quality. CONCLUSIONS: The assumption that there is a
      relationship between educational level and semen quality in men with asymptomatic
      varicocele seems well-founded, and educational level should therefore be
      considered as an explanatory variable in future investigations; studies are also
      required to provide a biological explanation of this phenomenon.

PMID- 7648063
TI  - Clinical outcomes associated with the implementation of a cost-efficient
      programme for radical retropubic prostatectomy.
AB  - OBJECTIVE: To develop and analyse a cost-containment programme for radical
      retropubic prostatectomy. PATIENTS AND METHODS: An in-depth analysis of the
      hospital charges associated with radical retropubic prostatectomy was conducted
      and a standard programme developed to control patient costs using a collaborative
      pathway method. The development of this programme and the outcomes of the first
      50 patients who underwent radical retropubic prostatectomy while on the
      collaborative care pathway system are summarized. RESULTS: The programme reduced
      both overall hospital charges per patient and the duration of hospital stay by
      44%. In addition, there was a significant reduction in the duration of surgery,
      intra-operative blood loss and the need for transfusion. Implementation of this
      programme had no apparent adverse effects on the rates of major or minor
      complications or hospital readmissions, and was accepted well by the patients.
      CONCLUSION: The collaborative care pathway developed for radical prostatectomy
      provides a system to deliver high quality, cost-efficient care in an environment
      which is highly acceptable to patients and which allows continued refinements in
      the care delivered.

PMID- 7648064
TI  - The blocking urinary catheter: the role of variation in urine flow.
AB  - OBJECTIVES: To relate blockage of the urinary catheter to urine chemistry.
      PATIENTS AND METHODS: Of 44 patients (age range 19-72 years) with an indwelling
      urinary catheter, 21 were troubled by frequent blockage and 23 experienced no
      blockage. Variation in urinary pH and calcium concentration were determined
      during a 24 h period and related to the occurrence of blockage using discriminant
      analysis. RESULTS: The maximum pH and calcium concentrations observed, or the
      maximum discriminant factors calculated, correctly discriminated 91% of patients
      (95% CI, 78-97%). CONCLUSION: Attention to volume and variability of fluid intake
      by the patient should have a major impact on the incidence of blockage of the
      indwelling urinary catheter.

PMID- 7648065
TI  - A method of measuring fluid balance during transurethral resection of the
      prostate.
AB  - OBJECTIVE: To design a practical system for non-invasively monitoring fluid
      balance during transurethral resection of the prostate (TURP) and other
      endoscopic procedures. MATERIALS AND METHODS: Load cell transducers are
      incorporated into a platform placed under the operating table. Output is passed
      to a digital weighmeter and then to a portable computer. The raw data is filtered
      using software written by the authors (CAL) and the output displayed both
      numerically and graphically on the computer screen. The device was tested under
      laboratory conditions and then assessed in the clinical setting. RESULTS: The
      device proved stable in both the laboratory and clinical settings. Examples of
      the common patterns generated during TURP are presented. The prototype has been
      used routinely in our practice to warn the surgeon and anaesthetist of fluid
      overload and has been used to monitor fluid balance in several studies.
      CONCLUSIONS: This instrument provides a practical method of monitoring total
      fluid balance during TURP. It can be used with either general or regional
      anaesthesia and provides information not otherwise available. It provides an
      early warning of significant changes in total fluid balance, particularly
      irrigant fluid absorption. Use of this device serves to prevent development of
      the TUR syndrome, a potentially fatal complication of endoscopic surgery. Our
      ultimate aim is to produce a refined version that is simple, compact and cheap
      enough to be used routinely in all urological theatres. The cost of a single
      episode of intensive care for a patient developing iatrogenic complications from
      irrigant absorption would offset the cost of such a device.

PMID- 7648066
TI  - Targeting of bladder cancer with monoclonal antibody NCRC48--a possible approach
      for intravesical therapy.
AB  - OBJECTIVE: To determine the localization of the anti-MUC1 mucin monoclonal
      antibody (mAb) NCRC48 to bladder cancer following intravesical administration.
      PATIENTS AND METHODS: mAb NCRC48 (330-500 micrograms) radiolabelled with
      111indium (11-17 MBq) was administered intravesically to 12 unselected patients
      with radiological evidence of bladder cancer. Tumour localization was assessed by
      gamma-camera imaging and by tissue biodistribution studies on biopsies obtained
      at cystoscopy at about 2 or 24 h after the procedure. After 24 h, whole blood
      radioactivity was measured and 3 weeks after the procedure the serum level of
      human anti-mouse antibodies was estimated using an ELISA method. RESULTS: Eleven
      patients had tumours confirmed at cystoscopy (grades 1-3, stages pTa-pT2). The
      mean uptake of NCRC48 by tumour and by normal urothelium (expressed as the
      percentage of the instilled dose/g x 10(3) +/- SD) at 2 h was 3.42 +/- 3.68 and
      0.41 +/- 0.77 (P < 0.05). After 24 h, the values for tumour and normal urothelium
      were 1.17 +/- 1.18 and 0.17 +/- 0.11, respectively. Areas of increased activity
      on the scintigrams were consistent with the position of the tumours at
      cystoscopy. No radioactivity was detected in blood at 24 h and there was no
      evidence of a human anti-mouse antibody response. CONCLUSION: The MUC1 mucin may
      be a suitable antigen to study the potential of therapeutic strategies based on
      monoclonal antibody targeting of superficial bladder cancer and may allow the
      development of more effective agents in the treatment of this condition.

PMID- 7648067
TI  - Reagent strip testing urine for significant bacteriuria in a urodynamic clinic.
AB  - OBJECTIVES: To determine the effectiveness of two reagent strips in detecting
      significant bacteriuria amongst patients attending for urodynamic assessment.
      PATIENTS AND METHODS: Four hundred patients undergoing urodynamic assessment were
      recruited for the study. Routine diagnostic catheter specimens of urine were
      tested for nitrite, leucocytes and protein. RESULTS: The leucocytes and nitrite
      strips had a high specificity rate of 99.5%. The frequency of significant
      bacteriuria in our population was 7% (n = 28). CONCLUSION: Culturing samples
      which test negative for these strips is unnecessary. Reagent strip testing of
      urine provides a cheap, rapid method of screening for infection.

PMID- 7648068
TI  - Pelvic floor exercises for children: a method of treating dysfunctional voiding.
AB  - OBJECTIVE: To evaluate the clinical effect of a pelvic floor exercise programme
      developed for children. PATIENTS AND METHODS: Sixteen girls with non-neurogenic
      dysfunctional voiding were treated by a physiotherapist, mostly in small groups.
      The exercises were designed to increase the child's awareness of their pelvic
      floor musculature and to teach them how to contract and relax these muscles at
      will. The emphasis on pelvic floor relaxation served to improve the child's
      voiding pattern. RESULTS: After 1 year, nine girls were cured and seven improved.
      Another three girls were cured at the 3-4 year follow-up, giving a total cure
      rate of 12/16. CONCLUSION: This non-invasive method seems to be a useful
      alternative or complement to other treatments of children with dysfunctional
      voiding.

PMID- 7648069
TI  - Hydration monitoring in the prevention of recurrent idiopathic urinary tract
      infections in pre-menopausal women.
AB  - OBJECTIVE: To assess whether the use of simple hydration monitoring can encourage
      adequate hydration and reduce urinary osmolality and the incidence of urinary
      tract infections (UTIs) in a population of susceptible pre-menopausal women with
      recurrent idiopathic urinary infections. SUBJECTS AND METHODS: The study included
      28 pre-menopausal women who had at least two idiopathic UTIs in the previous 6
      months. Urinary osmolality was assessed by the patients at each void by a simple
      hand-held probe, and the readings over 4 months compared. Monthly urine culture
      was compared between successive 4-month periods in which the probe was or was not
      used. RESULTS: The study was completed by 17 women. There was a significant shift
      towards urine of lower osmolality over the 4-month period using the probe
      (Pearson's chi 2 < 0.001). Significantly fewer urinary tract infections developed
      during the 4 months using the probe (McNemar's chi 2 = 0.046). CONCLUSIONS: The
      use of the osmolality probe encouraged the subject to maintain adequate
      hydration. The resulting augmentation of the natural urethral 'washout' mechanism
      led to lower osmolality urine and a reduction in the incidence of UTIs.

PMID- 7648070
TI  - Elevated mast cell tryptase in the urine of patients with interstitial cystitis.
AB  - OBJECTIVE: To investigate the number of tryptase positive bladder mast cells and
      the level of urine tryptase in interstitial cystitis (IC), a bladder disorder
      which occurs mostly in women and is characterized by suprapubic pain, frequency
      and nocturia. PATIENTS AND METHODS: Bladder biopsies from 37 women with IC and 15
      control women with other bladder conditions (age range 18-63 years) were obtained
      during diagnostic bladder distension and frozen immediately. Mast cells positive
      for tryptase were identified by immunohistochemistry and evaluated by light
      microscopy. Tryptase was measured by solid phase radioimmunoassay in urine
      samples, collected immediately (spot) and during a period of 24 h, obtained from
      normal women volunteers, controls and patients with IC. To adequately quantify
      tryptase, the physiologically active tetramer was dissociated to inactive
      monomers with supersaturated NaCl (6.0 M), and then dialysed. RESULTS: The
      patients' spot urine sample tryptase levels were indistinguishable from those of
      controls, which included the normal women volunteers. However, the tryptase
      levels in 24 h urine samples were greatly elevated only in patients with IC, both
      before (P < 0.005), and especially after NaCl treatment and dialysis (P < 0.001).
      CONCLUSION: These results indicate that the tryptase levels of 24 h urine
      samples, combined with methylhistamine levels and the clinical criteria presently
      used, may possibly help to better identify IC.

PMID- 7648071
TI  - Strategies for increasing nursing involvement in facility planning.
AB  - Environmental conditions and respect as the direct patient caregiver are
      important to nurse satisfaction. This author describes strategies which increase
      the nurses participation in redesigning their unit so that the new design helps
      them provide efficient nursing care.

PMID- 7648072
TI  - Overemphasized use of GPA for admission decisions.
AB  - When nursing schools have too many applicants for the number of students they can
      take, many use the cumulative Grade Point Average (GPA) as an important factor in
      the selection process. However, this practice continues to exclude students, many
      from minorities, which need to be included in preparing nurses to care for all
      populations. These authors describe how to use GPA only as an initial preliminary
      screening tool to determine qualified applicants, but not as a factor in the
      final decision in selecting students.

PMID- 7648073
TI  - Salary reductions: controversial approaches.
AB  - In this period of restructuring, salary reductions have increasingly become a
      choice for the manager facing a severely decreased budget. This nurse compares
      several strategies for accomplishing reductions and encourages managers to pick
      ones with the least disadvantages for patients and staff.

PMID- 7648074
TI  - Creating the role of the retention program coordinator.
AB  - During healthcare restructuring, nurse satisfaction can suffer. The following
      article describes how nurse executives and human resource professionals can
      implement a full- or part-time retention coordinator role for their healthcare
      facility. These authors describe how a retention coordinator can use formal and
      informal meetings to keep track of nurse satisfaction and develop strategies that
      identify and solve nurse satisfaction problems.

PMID- 7648075
TI  - Organizational transition: managing through rough waters.
AB  - Managing during restructuring is a little like managing during a tidal wave or an
      earthquake. The environment is turbulent, unpredictable, often personally
      threatening, and laden with long term consequences. As in a natural disaster, you
      must plan ahead, keep the short term in focus, and the long term in perspective.

PMID- 7648076
TI  - Interviewing and hiring LPNs: what to look for in the expanded LPN roles.
AB  - With the many changes in health care today, many facilities are redesigning and
      expanding the role of the Licensed Practical Nurse (LPN). This author shares
      successful interviewing and assessment strategies used when recruiting LPNs.

PMID- 7648077
TI  - How to handle rumors during restructuring.
AB  - The rumors are flying. The "facts" are being blown out of proportion and repeated
      out of context. People are asking, "Why does a good hospital like ours have to
      change?" And they are warning, "Patient care will suffer!" Welcome to the world
      of communicating during restructuring. The accelerated pace and huge scope of
      change in today's restructuring healthcare organizations require that you attack
      rumors and misrepresentation while you maintain a constant flow of accurate
      information.

PMID- 7648078
TI  - Job transition assistance for managers and executives: rekindling entrepreneurial
      spirit.
AB  - Management and executive positions are being combined or changed during
      restructuring. Although stressful, the transition offers opportunities for some
      managers and executives to look for new opportunities. Developing entrepreneurial
      spirit helps managers and executives make the transition.

PMID- 7648079
TI  - Getting the one new graduate you want: conducting a student experience evaluation
      conference.
AB  - In a time of downsizing and fewer available positions for new graduates, nurse
      managers and recruiters need more information to help them select the graduate
      that will best fit their organization. Student Experience Evaluation Conferences
      can help to provide this information. This article describes how to set up a
      student experience evaluation conference, leading to positive student experiences
      and improved retention.

PMID- 7648080
TI  - Developing the role of vice president of patient care services: pulling the
      clinical team together.
AB  - Making the transition from the traditional Nurse Executive role to Vice President
      of Patient Care Services can improve the quality of patient care while
      encouraging interdepartmental cooperation and streamlining the organization. This
      author who has experience coordinating two executive restructuring projects
      provides suggestions to ease the transition.

PMID- 7648081
TI  - Monitoring professionals' intent-to-leave: anticipating the effects of
      restructuring on future retention.
AB  - Staff who are dissatisfied with current restructuring changes are not leaving in
      large numbers, at least not yet. But, in some settings their intent-to-leave may
      be high enough that increased turnover might be next. Monitoring the intent-to
      leave now can help you reduce resignations later, when patient demand increases
      again.

PMID- 7648082
TI  - Sick leave: taking time off for family.
AB  - Sick leave, traditionally, has been for employees alone--a dissatisfying
      arrangement when the sick person is a family member, not the professional. But
      one hospital rewrote its rule, extending sick leave to include time off if a
      spouse or dependent child is ill. The staff likes the hospital's acknowledgment
      that professionals have important family obligations. Administrators like the
      high rate at which it's retaining valued personnel.

PMID- 7648083
TI  - Laparoscopic caecopexy for caecal volvulus.

PMID- 7648084
TI  - Randomized controlled trial of appendicectomy versus antibiotic therapy for acute
      appendicitis.

PMID- 7648085
TI  - Radiotherapy and the management of the axilla in early breast cancer.

PMID- 7648087
TI  - Splenic abscess.

PMID- 7648086
TI  - Retroperitoneal endoscopic adrenalectomy.

PMID- 7648088
TI  - Diagnosis and treatment of granulomatous mastitis.

PMID- 7648089
TI  - Simple method of tightening cutting setons.

PMID- 7648090
TI  - Endovascular repair of aortic aneurysm.

PMID- 7648091
TI  - Percutaneous transluminal angioplasty of infrainguinal vein graft stenosis: long
      term outcome.

PMID- 7648092
TI  - Parathyroid function following ligation of the inferior thyroid arteries during
      bilateral subtotal thyroidectomy.

PMID- 7648093
TI  - Breast reconstruction after mastectomy.

PMID- 7648094
TI  - Lymph node dissection in gastric cancer.

PMID- 7648095
TI  - New concepts in the pathophysiology of oxygen metabolism during sepsis.
AB  - Sepsis is an intriguing pathological condition associated with many complex
      metabolic and physiological alterations. In this review a novel hypothesis in the
      pathophysiology of oxygen metabolism during sepsis is explored. It is proposed
      that the hypermetabolic response to sepsis results from enhanced reactive oxygen
      generation by phagocytes. Reactive oxygen detoxification by host enzyme systems
      subsequently leads to alterations in oxidative metabolism. The similarities
      between the metabolic consequences of reactive oxygen metabolism and the
      metabolic changes observed during sepsis are outlined. A unified concept is
      presented to help explain the pathophysiological changes in oxygen metabolism
      during sepsis.

PMID- 7648096
TI  - Renal dysfunction in obstructive jaundice.
AB  - The association between renal dysfunction and obstructive jaundice is well
      established. Despite a substantial number of clinical reviews and prospective
      studies, the exact incidence and extent of the problem has not been determined
      accurately. Various pathogenic mechanisms and therapeutic strategies have been
      proposed but renal dysfunction remains a persistent problem in hepatobiliary
      practice. The intention of this review is to determine the current extent of the
      problem, outline the proposed pathophysiological mechanisms and assess the
      current therapeutic options.

PMID- 7648097
TI  - Lothian and Borders large bowel cancer project: immediate outcome after surgery.
      The consultant surgeons and pathologists of the Lothian and Borders Health
      Boards.
AB  - A prospective audit of all large bowel cancer resections is being conducted in
      the adjacent Health Boards of Lothian and Borders. The results of surgery in 750
      consecutive patients recruited during the first 2 years are presented. In this
      time, 249 (33.2 per cent) patients presented as an emergency, 490 (65.3 per cent)
      had resection of a colonic cancer, and 36 (4.8 per cent) patients died within 30
      days. Abdominal resection was performed in 741 patients and intestinal continuity
      was restored in 646 (87.2 per cent). Of all anastomoses performed, 31 (4.8 per
      cent) leaked (15 of 467 (3.2 per cent) and 16 of 179 (8.9 per cent) after
      resection of colonic and rectal cancers, respectively). Of the patients
      presenting with a rectal cancer, 251 (96.5 per cent) underwent abdominal
      resection and intestinal continuity was restored in 179 (71.3 per cent). Five of
      28 consultants were responsible for half of these patients. Patients treated by
      these five consultants were no more likely to undergo anastomosis, but when an
      anastomosis was performed it was less likely to leak (four of 95 (4.2 per cent)
      versus 12 of 84 (14.3 per cent) (chi 2 = 4.63, P < 0.05)). The overall outcome of
      surgery appears to be improved when compared to previous similar audits.
      Considerable intersurgeon variation remains in the results of resection of rectal
      cancer.

PMID- 7648098
TI  - Local excision and mucosal advancement for anorectal ulceration in patients
      infected with human immunodeficiency virus.
AB  - In patients infected with human immunodeficiency virus (HIV) no effective
      surgical procedure has been described for anorectal ulceration that is resistant
      to medical therapy. This study was designed to determine the effectiveness of
      surgical excision of anorectal ulcers, with or without mucosal advancement. The
      medical records of patients with HIV and anorectal pathology diagnosed between
      1984 and 1994 were reviewed. Patients with anorectal ulcers were divided into
      group A which was treated only with excision and group B in which excision was
      combined with mucosal advancement. Surgical treatment was considered successful
      if relief of symptoms was achieved within 4 weeks of the operation. Excision of
      anorectal ulcers was successful in seven of 16 patients (44 per cent) in group A.
      Relief of symptoms was achieved in 12 of 13 patients (92 per cent) in group B
      when surgical excision was combined with mucosal advancement, which is
      significantly better than the results in group A (P = 0.02). This non-randomized
      study indicates that after unsuccessful medical treatment persistent symptomatic
      ulcers should be treated operatively by excision with mucosal advancement.

PMID- 7648099
TI  - Seton treatment of perianal fistula with high anal or rectal opening.
AB  - Staged fistulotomy with a seton is considered to decrease the high incidence of
      continence disorders after surgical incision of a fistula. This retrospective
      study reports the results of the two-stage procedure with special emphasis on
      faecal continence. Thirty-four patients (aged between 20 and 57 years) were
      treated between 1981 and 1990 with a two-stage seton procedure for anal fistula
      (16 extrasphincteric and 18 trans-sphincteric) with a high anal or rectal
      internal opening. Thirty-one patients had normal preoperative continence. There
      were two recurrences. All trans-sphincteric fistulas healed. Twenty-nine patients
      with preoperative normal faecal control were available for follow-up.
      Postoperative continence was normal in 12 patients (category A according to
      Browning and Parks classification2); five patients had no control over flatus
      (B), 11 were incontinent for liquid stool or flatus (C) and one had continued
      faecal leakage (D). The two-stage seton technique is not recommended for fistulas
      with high anal or rectal openings.

PMID- 7648101
TI  - Colectomy as treatment for constipation in selected patients.
AB  - The aim of this study was to conduct a prospective assessment of the results of
      total abdominal colectomy and ileorectal anastomosis (TAC) in patients with
      colonic inertia. Overall, 416 patients were evaluated for chronic constipation.
      Of the patients 54 (13 per cent) had colonic inertia, defined as diffuse marker
      delay during transit study without paradoxical puborectalis contraction on
      cinedefaecography or electromyography. All 54 patients (42 women and 12 men),
      with a mean age of 49 (range 17-78) years, underwent TAC. Preoperative bowel
      frequency was a mean of one every 8 days, requiring large doses of laxatives,
      enemas or both. There was no major postoperative morbidity; five patients were
      readmitted due to bowel obstruction, three for successful conservative management
      while the other two required enterolysis. After a mean follow-up of 27 (range 2
      51) months these 54 patients reported a mean frequency of spontaneous bowel
      movements of 3.7 (range 1-10) per day. 'Excellent' or 'good' outcome was reported
      by 51 patients (94 per cent). TAC can be performed with acceptable morbidity and
      94 per cent of patients will have satisfactory improvement in bowel habit.

PMID- 7648100
TI  - Urethral catheterization causing incarceration of a previously reducible inguinal
      hernia.

PMID- 7648102
TI  - Use of the video-laparoscope to shed light on conventional pelvic dissection.

PMID- 7648103
TI  - Bilateral gluteus maximus transposition for anal incontinence.
AB  - Seven patients (five women and two men) with anal incontinence in whom previous
      surgery had failed, were treated by bilateral gluteus maximus transposition. All
      patients were incontinent to solid stool. Previous surgery was postanal repair in
      four women and secondary overlapping suture for obstetric tear in one. The two
      men were treated in childhood for anal atresia. No covering stoma was used. Wound
      infection occurred in three patients, requiring surgical drainage in two. After
      follow-up of more than 1 year three patients experienced improved continence but
      in four continence was unchanged. Anorectal physiology studies showed moderately
      increased resting and squeeze pressures in patients who were improved by the
      operation, but none could retain more than 200 ml of viscous fluid instilled into
      the rectum. No change in rectal sensitivity or volume tolerance was found. This
      preliminary series does not indicate that better results are obtained by gluteus
      maximus transposition than by unstimulated graciloplasty.

PMID- 7648104
TI  - Prospective audit of abdominal aortic aneurysm surgery in the northern region
      from 1988 to 1992. Northern Vascular Surgeons Group.
AB  - Over a 5-year period a prospective audit was carried out on 1131 patients
      undergoing surgery for abdominal aortic aneurysm (AAA) in the northern region. A
      total of 470 operations was performed in teaching hospitals and 661 in district
      hospitals; emergency operations accounted for 41.5 per cent. The overall
      mortality rate was 25.8 per cent; for emergency cases this value was 50.0 per
      cent. Mortality rates for elective surgery were 3.9 per cent in teaching and 12.0
      per cent in district hospitals. Patients with ruptured AAA admitted via the
      accident and emergency department had a higher mortality rate (64.3 per cent)
      than those admitted by their general practitioner (49.5 per cent) or those
      referred from the urology department (18.8 per cent). In all, 73 (6.5 per cent)
      patients were admitted with an alternative diagnosis, ranging from collapse of
      unknown cause (25) to torsion of the testes (one) and colonic obstruction (one).
      Age had a profound effect on mortality rates. For emergency cases the mortality
      rate varied from 47.0 per cent (in teaching plus district hospitals) in those
      aged less than 80 years to 70.1 per cent in those 80 years or over (chi 2 = 7.22;
      P = 0.007). For elective surgery the mortality rate varied from 7.6 per cent (in
      teaching plus district hospitals) in those under 80 years to 23.8 per cent in
      those 80 years or over (P = 0.0006). The overall mortality rate of 25.8 per cent
      is significantly less than that quoted in the Confidential Enquiry into
      Perioperative Deaths report of 1987. Furthermore, elective patients over 80 years
      of age may expect a survival rate of 76 per cent and, in the absence of major
      medical contraindications, should not automatically be denied surgery.
      Importantly, it is of note that this prospective audit identified 31 per cent
      more cases than recognized by regional audit data.

PMID- 7648105
TI  - Femoral exostosis presenting with deep vein and arterial thrombosis.

PMID- 7648106
TI  - Effect of low-dose dopamine on sigmoid colonic intramucosal pH in patients
      undergoing elective abdominal aortic aneurysm repair.
AB  - The effect of low-dose dopamine administration on intramucosal pH (pHi) of the
      sigmoid colon and on postoperative function of various organs in patients
      undergoing elective abdominal aortic aneurysm repair was examined. Nineteen
      patients were randomized to two groups; nine received dopamine at a rate of 3
      micrograms per kg per min for 24 h from induction of anaesthesia and ten control
      patients received fluids without dopamine. pHi was measured with a silicone
      tonometer and daily samples of blood were taken for measurement of liver
      transaminase activity, arterial oxygen saturation and creatinine concentration.
      Mean(s.e.m.) pHi fell to a significantly lower minimum value in those receiving
      dopamine compared with control patients (6.86(0.10) versus 7.11(0.08), P < 0.05).
      Five of the nine patients given dopamine developed intramucosal acidosis compared
      with only one of the ten control patients (P = 0.06). After operation the
      mean(s.e.m.) aspartate transaminase concentration in patients given dopamine rose
      from 33(2) to 80(17) units/l (P < 0.01); in control patients it rose from 32(3)
      to 59(16) units/l (P = 0.054). No differences between the groups was observed in
      the postoperative ratio of arterial oxygen saturation to inspired oxygen fraction
      or creatinine concentrations. These results indicate that dopamine has no
      beneficial effect on bowel mucosal oxygenation and function of the various organs
      in patients undergoing aortic aneurysm repair.

PMID- 7648107
TI  - Endoluminal transfemoral abdominal aortic aneurysm repair with aorto-uni-iliac
      graft and femorofemoral bypass.

PMID- 7648108
TI  - Assessment of feasibility for endovascular prosthetic tube correction of aortic
      aneurysm.
AB  - Abdominal aortic aneurysm (AAA) can now be corrected by perfemoral introduction
      of a prosthetic tube graft with fixation using expandable metal stents. This
      technique requires a satisfactory iliac system, through which the graft can reach
      its destination, and suitable lengths of non-aneurysmal aorta below the renal
      arteries and above the aortic bifurcation for stent attachment. The feasibility
      for placement of endovascular grafts was assessed in 44 consecutive patients
      admitted for transabdominal AAA repair. The proximal and distal aneurysmal necks
      and the iliac arteries were assessed before operation by colour flow Doppler
      ultrasonography (duplex scanning), computed tomography and intravenous digital
      subtraction angiography, using intraoperative measurements as the 'gold
      standard'. At operation 32 of 44 patients had a suitable proximal neck and five
      of 44 a suitable distal neck for endovascular grafting. Duplex scanning was the
      most accurate modality for preoperative assessment of the aneurysm necks.
      According to this technique 32 of 44 patients had a satisfactory iliac system for
      introduction of an endovascular graft. Overall only four of 44 patients were
      considered suitable for endovascular correction of AAA using a tube graft-stent
      combination.

PMID- 7648109
TI  - Laparoscopic repair of penetrating intra-abdominal injuries.

PMID- 7648110
TI  - Clinical and surgical aspects of double adenoma in patients with primary
      hyperparathyroidism.
AB  - The incidence of double parathyroid adenoma in 277 prospectively documented
      patients suffering from primary hyperparathyroidism was 5.4 per cent (15
      patients). Patients with double adenoma were all symptomatic and had a
      significantly higher parathyroid hormone (PTH) level and tumour weight than those
      with a solitary adenoma or four-gland hyperplasia. In 11 patients the adenomas
      were located bilaterally. Bilateral neck exploration must be performed routinely
      to deal successfully with this condition at initial operation. In six patients
      one enlarged gland was found in the thymus or posterior mediastinum. These
      locations should be explored, especially in patients with high PTH levels, in
      those in whom all four parathyroid glands cannot be detected or if only one small
      adenoma is found. In all such patients, selective resection of the enlarged
      parathyroid glands resulted in normocalcaemia (median follow-up 3.5 years).
      Selective resection of the pathological glands is the treatment of choice.

PMID- 7648111
TI  - Simple method of orientating breast biopsies following hook-wire or
      ultrasonographic localization of impalpable mammographic abnormalities.

PMID- 7648112
TI  - Prospective randomized trial of high versus low vacuum drainage after axillary
      lymphadenectomy.
AB  - A randomized prospective trial was performed to assess the effect of low versus
      high vacuum drainage after axillary lymphadenectomy. The mean(s.e.m.) volume of
      seroma evacuated with a low vacuum system was 386(26) ml (n = 38) compared with
      537(43) ml with a high vacuum system (n = 40) (P < 0.005). Low vacuum drains were
      removed earlier than high vacuum drains (P = 0.02). Seroma production after
      removal of the drains was not significantly different. The use of low vacuum
      drains after axillary dissection can reduce hospital stay.

PMID- 7648113
TI  - Analysis of 8651 appendicectomies in England and Wales during 1992.

PMID- 7648114
TI  - Anterior gastric wall stapling combined with posterior truncal vagotomy in the
      treatment of duodenal ulcer.
AB  - Anterior gastric stapling with posterior truncal vagotomy was examined as an
      alternative to highly selective vagotomy in the treatment of peptic ulcer
      disease. A clinical series of 32 patients who underwent the combined procedure is
      presented; gastric acid output was adequately reduced (basal output by 82 per
      cent, peak by 64 per cent). Motility changes were temporary and mild. Clinical
      follow-up, using a modified Visick grading, showed good to excellent results in
      21 of 25 patients who could be classified. This procedure is suggested as an
      appropriate alternative to highly selective vagotomy.

PMID- 7648115
TI  - Laparoscopic Nissen fundoplication is a satisfactory alternative to long-term
      omeprazole therapy.
AB  - A total of 168 patients with proven gastro-oesophageal reflux disease (GORD)
      receiving long-term medical therapy underwent laparoscopic Nissen fundoplication.
      The operation was converted to open fundoplication in four patients. All patients
      reported complete (92.3 per cent) or partial (7.7 per cent) relief of reflux
      symptoms 1 month after surgery. There were no associated deaths and the
      perioperative complication rate was 8.9 per cent. The mean(s.e.m.) length of
      operating time was 69.9(2.4) min and mean(s.e.m.) hospital stay 2.7(0.1) days.
      Symptom score assessment, 24-h oesophageal pH recording and lower oesophageal
      sphincter pressure showed significant (P < 0.0001) improvement 6 months after
      surgery in 85 evaluable patients. Before operation 37.5 per cent of the patients
      were considered symptomatically controlled on omeprazole and had excellent
      symptom control after surgery. This initial experience suggests that laparoscopic
      Nissen fundoplication is a safe and effective treatment for patients with GORD
      requiring long-term medication.

PMID- 7648116
TI  - Yield pressure, anatomy of the cardia and gastro-oesophageal reflux.
AB  - The yield pressure at which the cardia opens in response to gastric distension
      was measured in 155 subjects with and without gastro-oesophageal reflux (GOR) and
      after Nissen fundoplication. Yield pressure was measured by endoscopy or during
      oesophageal manometry. The median pressure was significantly lower in subjects
      with GOR than in those without (P < 0.0001). After successful Nissen
      fundoplication this pressure increased to supranormal values (P < 0.0001). There
      was a close relationship between yield pressure and the presence and size of
      hiatus hernia and also between yield pressure and the valvular appearance of the
      cardia at endoscopy. There was a significant correlation between yield pressure
      and oesophageal acid exposure. However, no relationship was observed between
      yield pressure and lower oesophageal sphincter pressure or intra-abdominal
      length. These results suggest that yield pressure is useful for assessment of the
      competence of the cardia, particularly after antireflux surgery. The competence
      of the cardia is greatly influenced by its anatomical structure.

PMID- 7648117
TI  - Small bowel obstruction caused by a retained percutaneous endoscopic gastrostomy
      gastric flange.

PMID- 7648118
TI  - Early gastric cancer: prognostic factors in 223 patients.
AB  - A retrospective study of 223 patients treated for early gastric cancer (EGC) is
      reported, representing 21.2 per cent of the 1051 patients with gastric cancer
      treated over the same period. Two main types of surgical procedure were used:
      subtotal resection of the stomach for EGC of the two lower thirds and total
      gastrectomy for lesions of the upper third. A lymphadenectomy of groups 1 and 2,
      according to the procedure of the Japanese Research Society for Gastric Cancer
      (R2 resection), was performed in all patients. The mean duration of follow-up was
      7.5 years. Univariate analysis showed a significant difference in survival rates
      only between patients with and without involved nodes (log rank = 6.05, P =
      0.0139). Other prognostic factors were not identified. A bivariate analysis was
      performed to evaluate the joint effect of node status and the Kodama
      classification: survival rates for patients with EGC of the penetrating (Pen) A
      type and node positive falls to around 57 per cent within 6 years. This group of
      patients has a tumour that should probably be considered as a 'non-early' lesion.
      To improve the survival of patients with a Pen A, node positive lesion, adjuvant
      chemotherapy may be appropriate.

PMID- 7648119
TI  - Laparoscopic Heller's cardiomyotomy without an antireflux procedure.
AB  - The treatment of achalasia by laparoscopic Heller's cardiomyotomy may combine the
      minimally invasive advantages of pneumatic dilatation with the success rate and
      low risk of perforation of conventional surgery. The requirement for an
      antireflux procedure remains a contentious issue, as in conventional surgery.
      Nine patients underwent laparoscopic cardiomyotomy; excellent symptomatic relief
      was obtained in eight at follow-up between 12 and 21 months after operation. Four
      of these patients agreed to 24-h pH monitoring and showed no evidence of acid
      reflux. One patient, however, developed recurrent symptoms associated with
      significant acidity on monitoring. Laparoscopic Heller's cardiomyotomy without an
      antireflux procedure produced effective symptomatic relief in this small group of
      patients.

PMID- 7648120
TI  - Correlation between expression of sialosyl-T antigen and survival in patients
      with gastric cancer.
AB  - Intestinal metaplasia of the gastric mucosa is an important lesion in the
      pathogenesis of gastric cancer. The expression of a mucin-associated antigen,
      sialosyl-T antigen, in the tissue of gastric cancer was investigated
      immunohistochemically to assess its biological role. Sialosyl-T antigen, detected
      by the monoclonal antibody TKH2, was present in 30 (23.6 per cent) of 127
      lesions, and expressed sporadically in intestinal metaplasia. Patients negative
      for sialosyl-T had a significantly better 5-year survival than those who were
      positive (70.4 per cent versus 47.2 per cent). Grading by sialosyl-T antigen
      expression and the DNA ploidy pattern had a predictive value for prognosis in
      patients with gastric cancer. The biological role of sialosyl-T antigen is not
      clear but the mucin alteration reflects upon the biological behaviour of gastric
      cancer.

PMID- 7648121
TI  - Tumour S-phase activity, nucleotide profile and RNA levels after hepatic artery
      occlusion and reperfusion in an experimental model of secondary liver carcinoma.
AB  - Rats with carcinoma of the colon implanted into the liver were subjected to
      hepatic arterial occlusion for 30-120 min. Regrowth of the tumour after
      reperfusion was evaluated by immunohistological determination of S-phase activity
      after injection of bromodeoxyuridine. Levels of RNA and nucleotides, and energy
      charge, were also examined. DNA synthesis was observed in the entire tumour
      except in necrotic areas of controls and after 30-min ischaemia with 2-h reflow.
      Almost all tumoral DNA synthesis was abolished by 2 h of ischaemia, except in a
      few cells in the tumour periphery, which after reperfusion for 22 and 40 h grew
      into a band-like concentric layer. Levels of energy charge, adenosine, uridine
      and guanosine 5'-triphosphates, and RNA were unchanged in liver tissue after
      hepatic arterial occlusion but decreased in the tumour. In conclusion 30 min of
      ischaemia did not damage the tumour cells substantially. Ischaemia for 2 h seemed
      able to kill the tumour cells except those in the periphery in areas nourished by
      the portal vein where tumour regrowth was seen. The liver tissue was not damaged.

PMID- 7648122
TI  - Introduction of laparoscopic cholecystectomy in a large teaching hospital:
      independent audit of the first 3 years.
AB  - Commencing with the introduction of laparoscopic cholecystectomy, a detailed
      independent prospective audit of all cholecystectomies attributable to 12 general
      consultant surgeons has been carried out over a period of 3 years. Of 650
      operations 502 were intended laparoscopic cholecystectomies. In the first year 58
      per cent were intended laparoscopic cholecystectomies; this rose to 80 per cent
      in the second year and to 90 per cent in the third. The conversion rate was 21
      per cent in the first year, 21 per cent in the second and 15 per cent in the
      third. The mean operating time for laparoscopic cholecystectomy was 133 min for
      year 1, 123 min for year 2 and 115 min for year 3, compared with 92, 101 and 95
      min respectively for open cholecystectomy. The overall complication rate was 10
      per cent for laparoscopic and 21 per cent for open cholecystectomy. This included
      six bile duct injuries (1.2 per cent) in the patients undergoing the laparoscopic
      procedure and one (0.7 per cent) in those having open cholecystectomy. This
      unselected audit of a group of general surgeons introducing laparoscopic
      cholecystectomy into their practice has revealed complication and conversion
      rates that are higher than those reported in most of the published literature,
      but may be representative of practice throughout the UK.

PMID- 7648123
TI  - Haemodynamic effects of pneumoperitoneum during laparoscopic cholecystectomy: a
      prospective comparative study using bioimpedance cardiography.
AB  - The haemodynamic effects of increased intra-abdominal pressure during
      laparoscopic cholecystectomy in 22 patients were compared with those in 11
      patients undergoing open cholecystectomy; bioimpedance cardiography was used for
      monitoring at predetermined time intervals. In the laparoscopy group stroke
      volume, cardiac and ejection velocity indices were significantly decreased and
      the total peripheral resistance index was significantly increased during the
      insufflation period when compared with preinsufflation and corresponding values
      in the group undergoing open operation. Routine intraoperative parameters such as
      heart rate and blood pressure did not show any significant change or indicate
      alterations in cardiovascular performance during laparoscopic procedures.
      Continuous non-invasive cardiovascular monitoring by bioimpedance cardiography
      may be useful in patients with limited cardiac function.

PMID- 7648124
TI  - Comparison between pylorus-preserving and Whipple pancreatoduodenectomy.
AB  - Between 1989 and 1993, 62 patients underwent Whipple pancreatoduodenectomy and 75
      pylorus-preserving pancreatoduodenectomy (PPPD); 35 patients in the first group
      and 37 in the second had pancreatic adenocarcinoma while 17 and 21 patients
      respectively had periampullary adenocarcinoma. The aim of this retrospective
      study was the comparison of operative outcome, nutritional recovery and survival
      of patients who underwent these two operations. No significant differences were
      found between the two groups in operative mortality or morbidity, duration of
      gastric aspiration and time to start of solid meals. Patients who underwent PPPD
      had a better nutritional recovery: the increase of both body-weight and serum
      albumin level at 6 months after discharge was significantly higher for those who
      had preservation of the whole stomach (P < 0.001 and P < 0.05 respectively). No
      significant difference in survival was found between the two procedures when
      patients with pancreatic or periampullary adenocarcinoma were analysed
      separately.

PMID- 7648125
TI  - Management of bile leaks after laparoscopic cholecystectomy.
AB  - The success of laparoscopic cholecystectomy has been tarnished by the increased
      risk of bile duct damage associated with the operation. Many of these injuries
      can be managed by endoscopic techniques. Experience of such injuries between 1991
      and 1994 was reviewed. Twenty-four patients were referred: 11 with injuries to
      the cystic duct alone, five with complete hepatic duct obstruction and eight with
      high bile duct leaks. All patients with leaks from the cystic duct were managed
      successfully endoscopically (sphincterotomy, four; stent, seven) without recourse
      to further surgery. Patients with complete obstruction were aided in their
      recovery by endoscopic and percutaneous techniques, either for postoperative
      problems (two patients) or in preparation for surgery (three). The eight patients
      with high bile duct leaks were managed endoscopically by stenting (seven
      patients) or sphincterotomy (one). Stenting appeared to encourage leaks to heal
      better than sphincterotomy alone; stents should probably be left in situ for 2
      months before removal. There were no deaths and all but one patient had normal
      biliary function at follow-up. It is suggested that all suspected injuries after
      biliary surgery require management by a combination of interventional radiology
      and endoscopic interventional techniques. Surgery may be required only if there
      is complete obstruction of the biliary tree.

PMID- 7648126
TI  - Giant diverticulum of the sigmoid colon.

PMID- 7648127
TI  - Transplantation for fulminant and subfulminant hepatic failure with preservation
      of portal and caval flow.
AB  - This article describes experience with preservation of portal and caval flow
      during orthotopic liver transplantation (OLT) for fulminant or subfulminant
      hepatic failure (FSHF) as an alternative to venous bypass. As a modification of
      the standard procedure, hepatectomy and graft implantation were performed with
      preservation of caval patency in combination with a temporary portocaval shunt.
      From July 1991 to March 1994, 25 consecutive patients with FSHF underwent OLT
      with preservation of portal and caval flow. All patients had severe confusion (n
      = 9) or coma (n = 16) with a mean(s.d.) clotting factor V of 13(5) per cent and a
      mean(s.d.) serum bilirubin level of 408(151) mumol/l. During the anhepatic phase,
      haemodynamic data showed a preservation of cardiac filling pressure, mean
      arterial pressure, and renal perfusion pressure, while the mean(s.d.) urine flow
      was maintained at 182(120) ml/h. Venous bypass was not required. There were three
      (12 per cent) deaths after the operation, and all survivors made a full
      neurological recovery. Normal postoperative creatinine values allowed the early
      use of baseline immunosuppression. The authors conclude that, in patients with
      FSHF, successful liver transplantation can be achieved with this technical
      procedure.

PMID- 7648128
TI  - Repeated liver resection for metastatic malignant schwannoma.

PMID- 7648129
TI  - Operative procedures in patients subsequently found to be human immunodeficiency
      virus positive.
AB  - This study investigated the number and range of surgical procedures performed in
      patients subsequently found to be human immunodeficiency virus (HIV) positive.
      Procedures were included if they occurred during a period when the patients were
      likely to have been infected with HIV but unaware of their HIV status. A total of
      28 operative procedures were documented in 19 (22 per cent) of 86 patients.
      Several operations were major and invasive. All patients had recognized risk
      factors for HIV infection but these had not been elicited in the surgical
      records. Women and patients who acquired their disease through heterosexual
      intercourse were more likely to have undergone surgery before a diagnosis of HIV
      than homosexual men. The incidence of surgical procedures in patients with HIV
      infection was significantly greater than in the general population of
      Leicestershire; however, many of these were minor and related to the management
      of complications associated with HIV. Surgeons are performing operations on
      patients who are unknowingly infected with HIV. The risk of transmission of HIV
      to surgeons is remote, but surgeons must be aware of risk factors for HIV
      infection.

PMID- 7648130
TI  - Laparoscopic adrenalectomy.

PMID- 7648131
TI  - Neoplastic lesions of the appendix.

PMID- 7648132
TI  - Postoperative pain relief.

PMID- 7648134
TI  - Diagnostic difficulties in patients with a ruptured bladder.

PMID- 7648135
TI  - Pelvic floor physiology in women with faecal incontinence and urinary symptoms.

PMID- 7648133
TI  - Laparoscopic cholecystectomy minimally impairs postoperative cardiorespiratory
      and muscle performance.

PMID- 7648136
TI  - Laparoscopic colonic surgery.

PMID- 7648137
TI  - Seat-belt compression appendicitis.

PMID- 7648139
TI  - Adjuvant therapy for pancreatic cancer.

PMID- 7648140
TI  - Surgical management of regional lymph nodes in primary cutaneous malignant
      melanoma.
AB  - The management of regional lymph nodes in the patient with primary cutaneous
      malignant melanoma remains a contentious issue. Early removal of nodes, which may
      harbour occult microscopic disease before the development of clinically
      detectable malignant lymphadenopathy, is thought by some to confer a survival
      advantage and/or improve locoregional tumour control. While tumour burden at
      lymphadenectomy has been shown to correlate with prognosis, there are conflicting
      reports regarding the efficacy of elective lymph node dissection (ELND) compared
      with a regimen of delayed therapeutic dissection for clinically detectable nodal
      involvement. Evaluation of arguments for and against ELND, together with
      consideration of surgical morbidity and the predictability of lymphatic drainage
      patterns, has allowed a clinical algorithm to emerge which may identify patients
      who may benefit from prophylactic surgery. A chronological summary of the
      relevant studies is presented and the overall division of opinion regarding the
      efficacy of ELND is discussed.

PMID- 7648138
TI  - Mobility after lower-limb amputation.

PMID- 7648141
TI  - Budd-Chiari syndrome.
AB  - Budd-Chiari syndrome is the generic term for different forms of hepatic venous
      outflow obstruction resulting in a clinical picture of portal hypertension and
      hepatomegaly. Three levels of venous outflow obstruction may be recognized,
      affecting respectively the small intrahepatic (IVC). Each level of obstruction is
      related to a different aetiology. Clinical manifestations range from mild
      symptoms to acute or chronic end-stage liver disease. Treatment is surgical in
      the great majority of patients. Occlusion of the IVC may be treated by removal of
      the caval obstruction in selected patients. Hepatic outflow obstruction may be
      circumvented by different forms of shunting from the portal or upper mesenteric
      vein to the IVC or right atrium, depending on the level of obstruction and the
      difference in venous pressure. For the rare patient presenting with acute or
      chronic end-stage liver failure, hepatic transplantation may be a life-saving
      procedure.

PMID- 7648142
TI  - Total mesorectal excision and local recurrence: a study of tumour spread in the
      mesorectum distal to rectal cancer.
AB  - Total mesorectal excision (TME) appears to be associated with a reduced local
      recurrence rate following surgery for rectal cancer. Of 20 patients with rectal
      cancer in whom TME was performed, adenocarcinoma was found in the distal
      mesorectum in four. Distal mesorectal spread often extended further than
      intramural spread. Patients with tumour in the distal mesorectum had a worse
      outcome at 4-year follow-up, a greater risk of local recurrence and an increased
      frequency of distant metastasis. Distal tumour spread is, therefore, a marker of
      poor prognosis in rectal cancer. This study provides further evidence that
      incomplete excision of the mesorectum contributes to local recurrence in a
      proportion of patients with rectal cancer, particularly in those with tumours in
      the middle and lower third of the rectum.

PMID- 7648143
TI  - Prospective randomized controlled trial of a micronized flavonidic fraction to
      reduce bleeding after haemorrhoidectomy.
AB  - A prospective randomized controlled trial was carried out on the effects of
      Daflon 500 mg (a micronized flavonidic fraction containing diosmin 450 mg and
      hesperidin 50 mg) on bleeding after haemorrhoidectomy. In all, 228 consecutive
      patients with prolapsed irreducible piles were recruited. Elective
      haemorrhoidectomy was performed with a standardized diathermy excision method.
      Some 114 patients were randomized to receive Daflon 500 mg for 1 week after
      operation (group 1), and there were 114 controls (group 2). Postoperative
      analgesia and laxative prescription as well as hospital stay were otherwise the
      same. One patient (0.9 per cent) from group 1 and seven (6.1 per cent) from group
      2 had postoperative bleeding (P = 0.03). All bleeding occurred from 6 to 15 days
      after haemorrhoidectomy. There were no side-effects from the use of Daflon 500
      mg. The risk of secondary bleeding from haemorrhoidectomy is reduced with
      postoperative Daflon.

PMID- 7648144
TI  - Early parietal recurrence of adenocarcinoma of the colon after laparoscopic
      colectomy.

PMID- 7648145
TI  - Living unrelated liver transplantation between spouses for fulminant hepatic
      failure.

PMID- 7648146
TI  - Retroperitoneoscopy and retroperitoneal colonic mobilization: a new approach in
      laparoscopic colonic surgery.

PMID- 7648147
TI  - Exercise capacity in patients undergoing proctocolectomy and small bowel
      resection for Crohn's disease.
AB  - The effect of proctocolectomy and small bowel resection on working capacity has
      not been assessed objectively in previous research. Twenty-nine patients with
      Crohn's disease were investigated with cycle ergometry and a questionnaire,
      following proctocolectomy with and without small bowel resection. Maximal
      exercise load is known to correspond well with working capacity, particularly
      when account is taken of body composition and metabolic variables. Maximal
      exercise load was reduced marginally (by 9 per cent) in patients without small
      bowel resection and by 22 per cent in patients with moderate small bowel
      resection (15-30 per cent resection). Patients with extensive bowel resection
      (more than 50 per cent) had a 40 per cent reduction in the maximal exercise load.
      This reduction in maximal exercise load was greater than predicted when
      accounting for reduction in muscle mass. All patients had a normal oxygen uptake
      including resting energy expenditure. Urinary sodium and magnesium excretion was
      low in the group with moderate bowel resection, whereas the extensively resected
      patients were malnourished and had a reduced body cell mass. The authors conclude
      that the significantly reduced working capacity was of multifactorial origin
      secondary to malabsorption. However, the patients seemed unaware of the degree of
      their diminished working capacity. This reduced capacity makes it unlikely that
      they would be able to perform any labour involving high energy consumption at the
      level of 500-700 W, and this inability was reflected by a high rate of
      unemployment among the patients.

PMID- 7648148
TI  - Value of oral antibiotic prophylaxis in colorectal surgery.
AB  - A total of 169 patients undergoing colorectal surgery were randomly allocated to
      receive either gentamicin plus metronidazole or oral ciprofloxacin plus
      metronidazole as prophylaxis; they were also allocated to receive cover for 1 or
      3 days. Twenty-eight patients (17 per cent) developed postoperative wound
      infections. The proportion of patients with wound infections and other infective
      complications was significantly less (P < 0.02) in those receiving oral
      ciprofloxacin. Cover for 3 days was no better than that for only 1 day. Oral
      ciprofloxacin for prophylaxis may offer advantages in efficacy and ease of
      administration compared with parenteral antibiotics.

PMID- 7648149
TI  - Simple method for very low colorectal anastomosis with the double staple
      technique.

PMID- 7648150
TI  - Efficacy of tumoricidal agents in vitro and in vivo.
AB  - Implantation of exfoliated tumour cells can give rise to local recurrence of
      colorectal cancer and it has been recommended that the bowel lumen be lavaged
      with a tumoricidal agent. This study identified which tumoricidal agents are
      currently used in Scotland and investigated their efficacy in vitro and in vivo.
      Cytotoxic efficacy was tested in vitro by a clonogenic assay and in vivo by a rat
      model with viable intraluminal tumour cells. Overall 70 per cent of surgeons used
      a tumoricidal agent during colorectal cancer surgery. Povidone-iodine, sodium
      hypochlorite and chlorhexidine-cetrimide were all effective at killing tumour
      cells in vitro but were all inactivated by the presence of 25 per cent whole
      blood in vitro. With 10(5) cells in vivo povidone-iodine and sodium hypochlorite
      significantly (P < 0.02) reduced the incidence of tumour growth while
      chlorhexidine-cetrimide had no significant effect. With 10(6) cells povidone
      iodine had no effect on the incidence of tumour growth. Tumoricidal agents have
      effective cytotoxicity in vitro but are only weakly cytotoxic in vivo.

PMID- 7648152
TI  - Prediction of local recurrence and survival of carcinoma of the rectum by
      surgical and histopathological assessment of local clearance.
AB  - The surgeon and histopathologist were asked to assess whether clearance of the
      resected primary rectal tumour was complete or not. The results of each
      assessment were related to survival and recurrence rates. Of 478 patients
      entered, full information was available for 396 who were followed to death or for
      at least 5 years. The surgeon and pathologist agreed on the clearance in 341 of
      the 396 patients. The 5-year local recurrence rate was 15 per cent in the 331
      patients with complete local clearance and 62 per cent in those with incomplete
      clearance. There was disagreement regarding 55 patients (14 per cent) (39
      pathologist 'incomplete'/surgeon 'complete'; 16 surgeon 'incomplete'/pathologist
      'complete'). Local recurrence occurred later where the pathologist assessed
      resection to be incomplete (log rank chi 2 = 11.0, 1 d.f., P = 0.001). Of 321
      patients without metastatic disease, the surgeon and pathologist agreed in 290
      that 284 had complete and six incomplete clearance. The 5-year survival rates
      were 53 and 0 per cent respectively. There was disagreement regarding 31 patients
      (10 per cent) (11 surgeon 'incomplete'/pathologist 'complete'; 20 pathologist
      'incomplete'/surgeon 'complete'). The 5-year survival rates were 18 and 10 per
      cent respectively (log rank chi 2 = 1.5, 1 d.f., P = 0.2). Surgical and
      histopathological assessments of local clearance are important in determining
      local recurrence and survival.

PMID- 7648151
TI  - Antibacterial activity of bowel-cleansing agents: implications of antibacteroides
      activity of senna.

PMID- 7648153
TI  - Ilioinguinal block dissection for malignant melanoma.
AB  - A retrospective analysis of 41 patients treated for metastatic inguinal lymph
      node malignant melanoma is presented: 16 underwent inguinal node excision and 25
      ilioinguinal node excision. The two groups were well matched for age, sex and
      other characteristics. The mean time in hospital (inguinal 20 days, ilioinguinal
      18 days) and the complication rates (inguinal, ten of 16 patients, ilioinguinal,
      13 of 25) were similar in each group. The incidence of groin relapse, defined as
      the development of symptomatic melanoma in the region of the inguinal or iliac
      node basins following block dissection, was lower after ilioinguinal block
      dissection (inguinal, three patients; ilioinguinal, none). Histological
      examination demonstrated a high proportion of iliac node involvement (13 of 25
      patients), even in those with a single mobile inguinal lymph node clinically and
      no clinical or computed tomographic evidence of iliac node involvement. This
      supports the value of ilioinguinal block dissection and suggests that the
      associated morbidity need not be greater than that associated with inguinal
      clearance alone.

PMID- 7648154
TI  - Exposure of the peritoneal cavity to air regulates early inflammatory responses
      to surgery in a murine model.
AB  - Factors in circulating air may play a role in immune responses after surgery
      through induction of gut-derived lipopolysaccharide (LPS) translocation across
      the gut. CD-1 mice were randomized to one of four treatment groups: controls,
      laparoscopy with carbon dioxide inflation, laparoscopy with air inflation and
      laparotomy. The peritoneal and systemic immune response was assessed by
      evaluating peritoneal macrophage, blood monocyte and neutrophil activity. In a
      second study, the effect of each of the treatments on fluorescein isothiocyanate
      (FITC)-LPS translocation across the gut was assessed. There were significant (P <
      0.05) increases in peritoneal tissue macrophage release of superoxide and tumour
      necrosis factor after laparoscopy with air and laparotomy compared with control
      procedures and carbon dioxide laparoscopy. However, peritoneal macrophage FITC
      Candida albicans ingestion was significantly decreased after air laparoscopy and
      laparotomy compared with controls and carbon dioxide laparoscopy (P < 0.05).
      These findings correlated with a significant (P < 0.05) decrease in CD11b
      expression. Significant translocation into the peritoneal cavity and systemic
      circulation occurred after air laparoscopy and laparotomy only. Factors in
      circulating air can induce LPS translocation and subsequent stimulation of
      postoperative immune responses. The beneficial effects of laparoscopic surgery
      may be explained by the minimal air contamination of the peritoneal cavity.

PMID- 7648155
TI  - Influence of screening on the incidence of ruptured abdominal aortic aneurysm: 5
      year results of a randomized controlled study.
AB  - From family medical practices 15775 men and women aged 65-80 years were
      identified and randomized into two groups: one group was invited for
      ultrasonographic screening for abdominal aortic aneurysm (AAA), and the other
      acted as age- and sex-matched controls. Of the 7887 invited for screening 5394
      (68.4 per cent) accepted. AAA was detected in 218 (4.0 per cent overall and 7.6
      per cent of men). Aortic surgery was offered to the screened group if certain
      criteria were met and no patient died from rupture who was fit for operation and
      accepted elective treatment. The incidence of rupture was reduced by 55 per cent
      in men in the group invited for screening, compared with controls. The incidence
      of rupture in women was low in both groups.

PMID- 7648156
TI  - Importance of hepatovenous back-perfusion for maintenance of liver viability
      during the Pringle manoeuvre.
AB  - The role of hepatovenous back-perfusion in maintaining hepatic viability was
      investigated during inflow occlusion (Pringle manoeuvre) of the pig liver. The
      study compared two ischaemia procedures of 60 min duration: hepatic inflow
      occlusion and inflow plus outflow occlusion (vascular exclusion). Each procedure
      was carried out in six pigs and liver tissue perfusion, energy metabolism, lipid
      peroxidation and 7-day survival were assessed. Although all pigs survived after
      inflow occlusion, five of six died after vascular exclusion (P < 0.01). Exclusion
      induced a significant decrease in perfusion to 15.3 per cent of the value before
      ischaemia compared with 32.4 per cent after hepatic inflow occlusion alone (P <
      0.01). Although cellular adenosine 5'-triphosphate levels were significantly
      decreased by ischaemia in both groups, the fall was less in pigs with inflow
      occlusion alone (to 55 per cent of the preclamp value) than in those with
      exclusion (to 24 per cent of the preclamp value) (P < 0.01). The plasma
      phosphatidylcholine hydroperoxide level rose immediately after reperfusion in
      pigs with exclusion, while the level remained constant after inflow occlusion
      alone. There is a fundamental difference between the two ischaemia procedures:
      back-perfusion from the vena cava contributes to the maintenance of liver
      function during inflow occlusion.

PMID- 7648157
TI  - Experimental study to show that growth hormone treatment before trauma increases
      glutamine uptake in the intestinal tract.
AB  - This study examined whether growth hormone treatment deprived the intestinal
      tract of glutamine after trauma. Piglets were treated with growth hormone 24
      units daily 3 days before and at the start of the trauma (GH-3, n = 8) or at the
      start of the trauma only (GH-1, n = 8). Eight piglets acted as non-treated
      controls. The trauma consisted of a standardized abdominal surgical procedure.
      Primed constant infusions of U-14C-glutamine were given. Intestinal, hepatic,
      renal and hindleg glutamine fluxes were measured. Growth hormone treatment
      increased mean(s.e.m.) net intestinal glutamine uptake: GH-3, 39.7(9.4) and
      48.7(12.7) mumol/min; GH-1, 33.2(5.5) and 25.7(12.3) mumol/min; controls,
      19.5(10.3) and 2.0(15.3) mumol/min at 1 h and 5 h after trauma, respectively, (P
      = 0.02). The treatment increased glutamine oxidation (P = 0.025), and decreased
      hindleg glutamine net (P = 0.0052) and absolute release (P = 0.0063), glutamine
      rate of appearance (P = 0.01), and percentage of glucose coming from glutamine (P
      = 0.05). Growth hormone treatment before trauma increased intestinal glutamine
      uptake.

PMID- 7648158
TI  - Randomized comparison of polyglycolic acid and polyglyconate sutures for
      abdominal fascial closure after laparotomy in patients with suspected impaired
      wound healing.
AB  - A randomized study of abdominal fascial closure using interrupted polyglyconate
      and polyglycolic acid sutures after laparotomy was carried out in 204 consecutive
      patients with suspected impaired wound healing. There were no statistically
      significant differences between the two sutures with regard to the development of
      fascial disruption and incisional hernia. Wound infection demanding surgical
      intervention was found in 7 per cent of patients with polyglyconate sutures and
      in 16 per cent of those with polyglycolic acid sutures (P = 0.04). Monofilament
      polyglyconate suture does not reduce the incidence of fascial disruption and
      incisional hernia after laparotomy in patients with suspected impaired wound
      healing but the incidence of wound infection may be reduced compared with that of
      multifilament polyglycolic acid suture.

PMID- 7648159
TI  - Total thyroidectomy in the treatment of thyroid carcinoma in childhood.
AB  - Between 1974 and 1993 ten girls and six boys aged 6-16 years underwent total
      thyroidectomy, with therapeutic selective neck dissection in six patients. All
      were treated after operation with radioactive iodine (131I) for ablation of
      thyroid tissue remnants. Papillary carcinoma occurred in ten patients, follicular
      carcinoma in two and medullary thyroid lesions in four. The patients were
      followed for a median of 11.5 (range 1-20) years with regular determinations of
      serum thyroglobulin levels and 131I whole-body scanning when indicated. Only one
      patient had a slight increase in thyroglobulin levels without evidence of disease
      on further screening. In children with medullary lesions the serum levels of
      basal and pentagastrin-stimulated calcitonin remained normal. Currently all
      patients are alive and without disease. Hypocalcaemia lasting for more than 1
      year was observed in one patient. Recurrent nerves were not injured accidentally,
      but because of tumour invasion two of 32 recurrent nerves had to be sacrificed.
      This surgical approach is safe and well tolerated in children.

PMID- 7648160
TI  - Hereditary breast cancer and linkage analysis to BRCA1.
AB  - In this study, over 1000 women with breast cancer were contacted by questionnaire
      and 164 families with a strong history of breast cancer were identified. Home
      visits to obtain full pedigree details took place for 123 women, and members of
      24 families gave venous blood samples. The extracted DNA was typed by polymerase
      chain reaction amplification and the derived haplotypes submitted to linkage
      analysis which confirmed that in 12 families breast cancer susceptibility could
      be traced to BRCA1. The study demonstrates the number of women at risk of breast
      cancer in the population, illustrates the complexity of genetic analysis for
      hereditary breast cancer and demonstrates the problems of predictive analysis in
      clinical management.

PMID- 7648161
TI  - Upper-limb arterial disease in women treated for breast cancer.
AB  - A 5-year cohort of patients treated 15-19 years previously for breast cancer was
      studied to establish the prevalence of symptoms and objective evidence of
      circulatory insufficiency in the upper limbs. There were 187 survivors of the
      original cohort of 665. In all, 102 patients were evaluated; 50 had received
      radiotherapy in addition to surgery. Irradiated and non-irradiated groups were
      comparable for age, extent of axillary dissection and vascular risk factors. Both
      arms were assessed for symptoms and examined by Doppler ultrasonographically
      derived segmental pressures and hyperaemia testing, Doppler ultrasonographic
      waveform analysis, pulse volume recording and venous outflow air plethysmography.
      Seven ipsilateral arms (14 per cent) in patients given radiotherapy were
      symptomatic, compared with four (8 per cent) in those receiving surgery alone,
      and two contralateral control arms (2 per cent). Evidence of arterial disease was
      found in 11 ipsilateral arms of patients given radiotherapy (22 per cent) and two
      ipsilateral arms of those receiving surgery alone (4 per cent) (P < 0.03). There
      was no association between symptoms and evidence of arterial disease, and no
      evidence of abnormal venous function.

PMID- 7648162
TI  - Multivariate analysis of histopathological features as prognostic factors in
      patients with papillary thyroid carcinoma.
AB  - A retrospective analysis of 121 papillary thyroid carcinomas was made to assess
      prognostic factors including histological variants which might be related to
      survival. The mean follow-up period was 10 years and clinical, surgical and
      histopathological data were studied. The survival curves were analysed by the
      Kaplan-Meier method and the multivariate analysis used Cox's regression model.
      Eighty-seven patients had well differentiated papillary cancers. The survival
      rate for papillary thyroid cancer was 86 per cent at 5 years and 72 per cent at
      10 years. Factors showing prognostic significance for survival were tumour size,
      extrathyroid extension and histological type. Disease-free survival was
      influenced by sex, existence of a capsule and nodal metastases. Factors showing a
      favourable prognosis were: age under 45 years, size less than 4 cm, no
      extrathyroid extension and well differentiated histological type (P < 0.001).
      Histological subtype was one of the most important prognostic factors.

PMID- 7648163
TI  - Follicular carcinoma of the thyroid gland in Hong Kong Chinese.
AB  - A total of 64 Chinese patients (eight men, 56 women) undergoing primary treatment
      for follicular thyroid cancer between 1961 and 1986 were studied retrospectively
      to report the local experience in treatment of this condition and to identify the
      risk factors for mortality. The minimum follow-up was 7 (median 14) years. The
      mean tumour size was 3.0 (range 0.1-11.0) cm. The majority of patients (91 per
      cent) underwent total or near-total thyroidectomy. Distant metastases were
      detected in ten patients at the time of initial diagnosis and in three during
      follow-up. Locoregional recurrence had developed in six patients at follow-up.
      There were 13 deaths, with a median survival of 45 months. The 5- and 10-year
      survival rates were 87 and 80 per cent respectively. Six risk factors for
      mortality were selected for multivariate analysis using logistic regression; the
      presence of distant metastasis was the only significant risk factor for survival.

PMID- 7648164
TI  - Effect of aberrant hepatic arterial anatomy on tumour response to hepatic artery
      infusion of floxuridine for colorectal liver metastases.
AB  - Regional hepatic artery infusion of colorectal liver metastases produces the
      highest reported treatment response. The effect of variation in hepatic artery
      anatomy on tumour response to regional floxuridine (FUdR) was studied. Aberrant
      hepatic arterial anatomy occurred in 13 of 74 patients (18 per cent) who
      underwent cannulation of the hepatic artery and infusion of FUdR for colorectal
      liver metastases. The non-dominant hepatic artery was ligated and the dominant
      artery cannulated in those with aberrant anatomy. Despite evidence of a
      collateral circulation to the non-dominant area of the liver in these patients,
      there was no significant reduction in median tumour volume with treatment (before
      treatment 214 ml, after treatment 339 ml). By contrast, there was a significant
      (P < 0.001) decrease in median tumour volume (before treatment 329 ml, after
      treatment 148 ml) in those with normal anatomy. Delivery of FUdR to metastases
      via an intrahepatic collateral circulation was not as effective as through a main
      hepatic artery.

PMID- 7648165
TI  - Tissue factor expression correlates with histological grade in human pancreatic
      cancer.
AB  - The transmembrane cellular receptor tissue factor (TF) is the primary initiator
      of the coagulation cascade in man. Expression of TF was determined in 55
      specimens of ductal adenocarcinoma of the pancreas and was found to correlate
      strongly with the degree of histological differentiation. A significant linear
      trend was observed with stronger immunoreactivity observed in poorly
      differentiated tumours (chi 2 = 6.69, P = 0.0098). No TF staining was seen in
      pancreatic samples from normal controls (n = 18). As expression of TF may be
      associated with tumour progression, its analysis could provide useful prognostic
      information in patients with pancreatic malignancy.

PMID- 7648167
TI  - Safe decompression of hepatic hydatid cyst with a laparoscopic surgiport.

PMID- 7648166
TI  - Liver resection without blood transfusion.
AB  - A retrospective study was carried out of 522 elective liver resections to
      determine the impact of blood transfusion on the immediate postoperative outcome
      and on long-term survival. The number of liver resections without transfusion has
      increased in recent years, as a result of improvement in surgical technique with
      less blood loss during operation and more careful choice of the timing of
      transfusion. In resections carried out in the past 5 years, the indication for
      intraoperative transfusion was restricted and the decision was made jointly by
      the surgeon and anaesthetist, and in any case only if the haematocrit was below
      25 per cent. Of resections carried out in the past 2 years, 59 per cent did not
      require intraoperative transfusion. Postoperative deaths and complications were
      related to blood transfusion, particularly in patients with cirrhosis, in whom
      stepwise logistic regression analysis showed that transfusion was the only factor
      that correlated significantly with complications. Transfusion also affected the
      long-term survival of patients operated on for hepatocellular carcinoma and
      colorectal carcinoma metastases in univariate analysis and was the only factor
      shown by multivariate analysis to correlate with survival for hepatocellular
      carcinoma in patients with cirrhosis.

PMID- 7648168
TI  - Functional gastric impairment in carcinoma of the pancreas.

PMID- 7648169
TI  - Inflammatory bowel disease in primary sclerosing cholangitis: an analysis of
      patients undergoing liver transplantation.
AB  - Fifty-five patients undergoing orthotopic liver transplantation (OLT) for primary
      sclerosing cholangitis (PSC) were reviewed retrospectively. After OLT there were
      significantly more episodes of acute rejection in 31 patients with a previous
      history of inflammatory bowel disease (IBD) than in 24 without such a history.
      Patients who had severe acute rejection were significantly younger at diagnosis
      of IBD. Five patients with histological features suggestive of recurrent PSC
      after OLT were significantly younger at the time of transplantation than those
      who did not develop recurrence. Patients with poor control of IBD after OLT had a
      significantly lower age at diagnosis of bowel inflammation. The presence of IBD
      did not affect the outcome after OLT, but was associated with a higher rate of
      acute rejection. Younger patients had a greater risk of developing severe
      rejection, recurrent PSC and poor control of IBD after liver transplantation.

PMID- 7648170
TI  - Healing process of sutureless choledochojejunostomy in an experimental model.
AB  - The healing characteristics and morphological features of sutureless
      choledochojejunostomy were investigated in a rat experimental model. The common
      bile duct of 34 conditioned Wistar rats was exposed, divided transversely and a
      choledochojejunostomy constructed with only a vinyl chloride tube positioned
      between the common duct and jejunum. The animals were killed 4, 12 and 52 weeks
      after surgery. Cholangiographic evaluation of the anastomosis in all three groups
      showed wide openings with dilatation of the extrahepatic bile duct. Microscopic
      examination of the anastomosis showed hyperplastic changes of the bile duct
      epithelium. The epithelial defect was completely covered with proliferative
      epithelium 12 weeks after operation. At long-term follow-up of 52 weeks there
      were no biliary strictures after the sutureless technique. This surgical approach
      may be useful for patients in whom sutured anastomosis of the bile duct might
      lead to stricture, such as those with a normal thin-walled bile duct.

PMID- 7648171
TI  - Role of nitric oxide in lung injury associated with experimental acute
      pancreatitis.
AB  - This study evaluated the effect of varying the synthesis of nitric oxide with
      sodium nitroprusside or N-nitro-L-arginine methyl ester (L-NAME) in a
      pancreatitis-lung injury model. Rats (n = 45) were randomized to control or
      caerulein-induced pancreatitis groups, treated with saline, sodium nitroprusside
      (0.4 micrograms/kg) or L-NAME (10 mg/kg). Myeloperoxidase activity was used as a
      measure of neutrophil infiltration. Wet to dry (W:D) lung weight and
      bronchoalveolar lavage (BAL) protein concentrations were used to assess vascular
      leakage. Pancreatitis was shown to induce pulmonary neutrophil influx:
      mean(s.e.m.) myeloperoxidase activity 6.79(0.5) units/g in caerulein-treated
      animals versus 2.08(0.5) units/g in controls (P < 0.001). Animals with
      pancreatitis showed increased microvascular leakage compared with controls
      (mean(s.e.m.) W:D lung weight 7.01(0.5) versus 2.85(0.2), P < 0.001; BAL protein
      concentration 2539(222) versus 347(32) micrograms/ml, P < 0.001). Compared with
      the saline-treated pancreatitis group, these changes were reduced by sodium
      nitroprusside (mean(s.e.m.) myeloperoxidase activity to 2.5(0.4) units/g, P <
      0.001; W:D lung weight to 3.8(0.37), P < 0.001; BAL protein concentration
      1389(182) micrograms/ml, P < 0.05). L-NAME exacerbated the pancreatitis-induced
      pulmonary oedema (W:D lung weight increased to 11.96(0.6), P < 0.001), protein
      leakage (BAL protein concentration rose to 3707(309) micrograms/ml, P < 0.05) and
      neutrophil infiltration (myeloperoxidase activity increased to 9.01(0.3) units/g,
      P < 0.05). These data suggest that, in vivo, nitric oxide inhibits pancreatitis
      induced lung injury, possibly in part by inhibiting pulmonary neutrophil influx.

PMID- 7648172
TI  - Further experience with laparoscopy and peritoneal cytology in the staging of
      pancreatic cancer.
AB  - A total of 114 patients with pancreatic cancer and no evidence of metastatic
      disease by computed tomography underwent laparoscopy. Intra-abdominal spread was
      present in 27 patients (24 per cent). Metastases were 2.4 times more common in
      tumours of the distal pancreas (11 of 25, 44 per cent) than in pancreatic head
      tumours (16 of 89, 18 per cent) (P < 0.05). None of the 27 patients with
      metastases underwent further surgery. Of the 87 patients without metastatic
      spread, 42 were found to have vascular invasion by angiography and were offered
      radiation therapy. Thirty of 40 patients explored surgically were resected; two
      of the remaining ten had peritoneal spread that had been missed at laparoscopy
      (false-negative rate of 7 per cent). Cytological examination of peritoneal
      washings was performed in 94 patients at the time of laparoscopy; cytology was
      positive in 16 (17 per cent). There was a significant correlation between
      positive cytology and presence of visible liver or peritoneal metastases (ten of
      22 with metastases versus six of 72 without, P < 0.001). Positive cytology was
      present in six patients (8 per cent) without visible metastases, but none had
      resectable disease.

PMID- 7648173
TI  - Selective preoperative endoscopic retrograde cholangiopancreatography in
      laparoscopic biliary surgery.
AB  - The management of common bile duct (CBD) stones in patients subjected to
      laparoscopic cholecystectomy is still a subject of debate. A prospective study
      was performed of all 699 patients with symptomatic gallstones at risk of CBD
      stones between mid-1987 and 1994. Based on clinical, biochemical and
      ultrasonographic criteria, 119 patients underwent preoperative endoscopic
      retrograde cholangiopancreatography (ERCP) with or without endoscopic
      sphincterotomy. Results showed a high positive predictive value (over 85 per
      cent) for the presence of CBD stones in patients with acute cholangitis,
      persistent obstructive jaundice or in the acute phase of gallstone pancreatitis.
      In the other groups (increased liver enzyme levels, a wide CBD and after
      resolution of jaundice or pancreatitis) the positive predictive value was less
      than 25 per cent. The complication rate of ERCP with sphincterotomy was 14 per
      cent with a mortality rate of 2 per cent. These results argue for more selective
      use of preoperative ERCP only for patients with acute cholangitis, persistent
      jaundice or acute gallstone pancreatitis. Other patients at risk of harbouring
      CBD stones should undergo intraoperative laparoscopic cholangiography and, if
      stones are found, laparoscopic exploration of the bile duct or postoperative
      ERCP.

PMID- 7648174
TI  - Technique for closure of port sites under laparoscopic visual control.

PMID- 7648175
TI  - Effective administration of heparin and antibiotic prophylaxis.
AB  - A prospective audit was performed to determine whether new departmental
      procedures had improved the administration of heparin and antibiotic prophylaxis
      in patients undergoing major surgery who were at risk of deep vein thrombosis,
      pulmonary embolism and postoperative wound infection. The results are compared
      with a previous retrospective audit of the same 'at-risk' groups. A significant
      improvement in prophylaxis administration is demonstrated.

PMID- 7648176
TI  - Restoration of intestinal continuity following Hartmann's procedure: the Lothian
      experience 1987-1992.

PMID- 7648177
TI  - Restoration of intestinal continuity following Hartmann's procedure: the Lothian
      experience 1987-1992.

PMID- 7648181
TI  - Acute management of subclavian vein thrombosis.

PMID- 7648179
TI  - Inadequate levels of metronidazole in subcutaneous fat after standard
      prophylaxis.

PMID- 7648178
TI  - Restoration of intestinal continuity following Hartmann's procedure: the Lothian
      experience 1987-1992.

PMID- 7648180
TI  - Carcinoma in a colon J pouch reservoir after low anterior resection for villous
      adenoma.

PMID- 7648182
TI  - Helicobacter pylori infection in perforated peptic ulcer disease.

PMID- 7648183
TI  - Kidney retrieval from asystolic donors: a valuable and viable source of
      additional organs.

PMID- 7648184
TI  - Pathogenesis and prevention of adhesion formation.

PMID- 7648185
TI  - Port site metastases after laparoscopic colorectal surgery for cure of
      malignancy.

PMID- 7648186
TI  - Port site metastasis after laparoscopic colorectal surgery for cure of
      malignancy.

PMID- 7648187
TI  - Laparoscopy in the management of patients with cancer of the gastric cardia and
      oesophagus.

PMID- 7648188
TI  - Fatal intestinal ischaemia following laparoscopic cholecystectomy.

PMID- 7648189
TI  - Diagnosis and treatment of granulomatous mastitis.

PMID- 7648190
TI  - Bile duct injury and bile leakage in laparoscopic cholecystectomy.

PMID- 7648191
TI  - Prospective trial comparing Lichtenstein with laparoscopic tension-free mesh
      repair of inguinal hernia.

PMID- 7648192
TI  - Prospective trial comparing Lichtenstein with laparoscopic tension-free mesh
      repair of inguinal hernia.

PMID- 7648193
TI  - Prospective trial comparing Lichtenstein with laparoscopic tension-free mesh
      repair of inguinal hernia.

PMID- 7648194
TI  - Prospective trial comparing Lichtenstein with laparoscopic tension-free mesh
      repair of inguinal hernia.

PMID- 7648195
TI  - Prospective trial comparing Lichtenstein with laparoscopic tension-free mesh
      repair of inguinal hernia.

PMID- 7648196
TI  - Metallophthalocyanines as possible lignin peroxidase models.
AB  - Several metalloporphyrins, particularly highly chlorinated water soluble meso
      tetraphenylporphyrins, have been shown to be good biomimetics of the lignin
      peroxidases which degrade lignin in vivo. Metal complexes of the water soluble
      phthalocyaninetetrasulfonic acid have been examined as catalysts for the
      oxidation of lignin since the phthalocyanines are readily available and
      inexpensive. The copper(II), nickel(II) and cobalt(II) complexes showed little
      catalytic activity towards the oxidation of veratryl alcohol (a substrate of the
      lignin peroxidases). The iron(III) and manganese(III) complexes on the other hand
      were able to catalyze the oxidation of veratryl alcohol, 4-ethoxy-3-methoxyphenyl
      glycerol-beta-guaiacyl ether (a beta-O-4-dimer) and 1-(4-ethoxy-3-methoxy)-2-(4
      methoxyphenyl)-1,3-propanediol (a beta-1 dimer). These catalysts are, however,
      much less stable than the halogenated meso-tetraphenylporphyrins and this lower
      stability, which is dependent upon pH and the oxidant, limits their use as
      catalysts.

PMID- 7648198
TI  - Conversion of aldonic acids to their corresponding 2-keto-3-deoxy-analogs by the
      non-carbohydrate enzyme dihydroxy acid dehydratase (DHAD).
AB  - Aldonic acids containing four to six carbon atoms were tested as potential
      substrates of dihydroxy acid dehydratase (DHAD), an enzyme from the biosynthetic
      pathway of branched chain amino acids. Novel assay systems for observing the
      course of DHAD catalysed reactions were developed in order to adapt the enzyme to
      extended practical applications. Kinetic studies for the new substrates (12/13)
      as well as inhibitor kinetics for the substrate analogue 3-deoxy-aldonic acids
      (25, 27 and 29) were performed. These gave indications for the restrictions of
      substrate modifications and contributed to the understanding of the individual
      effects. Finally L-threonic acid (12) and D-erythronic acid (13) could be
      successfully applied as substrates for DHAD and this led to the chemoenzymatic
      synthesis of their 2-keto-3-deoxy-analogue (20) in a preparative scale.

PMID- 7648197
TI  - Subtilisin and alpha-chymotrypsin catalyzed synthesis of peptides containing
      arginine and lysine p-nitroanilides as C-terminal moieties.
AB  - p-Nitroanilides of N-acylated di-, tri- and tetrapeptides with C-terminal
      arginine or lysine residues have been obtained, as a rule with good yields, via
      acylation of arginine or lysine p-nitroanilides by methyl esters of respective N
      acylated peptides, catalyzed by subtilisin or alpha-chymotrypsin. The synthesis
      might be performed by two routes--by reaction in water-organic solvent mixtures,
      catalyzed by dissolved enzyme, or by condensation of the components in organic
      solvents with low water content in the presence of any enzyme distributed over a
      silica support surface. The second approach seems to be preferable due to
      suppression of hydrolytic side reactions and improved stability of an enzyme.
      Subtilisin 72 is especially effective as a catalyst for the acylation of p
      nitroanilides by N-protected tripeptide methyl esters--the derivatives capable of
      occupying the S1, S2 and S3 subsites of its extended binding site. Even dipeptide
      esters with D-amino acids in P2 position can be applied for p-nitroanilide
      acylation. The efficiency of alpha-chymotrypsin as a catalyst for peptide
      synthesis is more limited due to restricted specificity of this enzyme.

PMID- 7648199
TI  - Synthesis and vasodilator effects of 3- and 7-sulfonylurea-1,2,4-benzothiadiazin
      1,1-dioxides on rat aorta.
AB  - A series of substituted-1,2,4-benzothiadiazin-1,1-dioxide derivatives was
      designed and synthesized as potassium channel modulators. Various sulfonylurea
      moieties were introduced on positions 3 and 7 of the heterocycle without, or by
      means of, methylene and phenyl spacers. On rat aortic rings, several compounds
      displayed vasodilating activities, especially compound 24, which was more active
      than cromakalim and diazoxide at low doses (0.1 microM) and more active than
      diazoxide between 1 and 10 microM.

PMID- 7648200
TI  - Synthesis of 16-(bromoalkyl)-estradiols having inhibitory effect on human
      placental estradiol 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD type 1).
AB  - The activity of 17 beta-HSD type 1, the enzyme that converts estrone into its
      more potent metabolite estradiol, has been demonstrated in all classical
      steroidogenic tissues and almost all peripheral tissues from both rat and human.
      Since 17 beta-HSD is one of the most important enzymes involved in active steroid
      hormone formation, its inactivation could be a clinical approach to the treatment
      of hormono-dependent diseases like breast cancer. Herein we report the synthesis
      of 16-(bromoalkyl)-estradiols and their potency to inhibit the human placenta
      cytosolic estradiol 17 beta-HSD (type 1). Synthetic analogues possess various
      side chain lengths and orientation (alpha or beta) at position 16 of the
      steroidal D ring. The most potent inhibitory effect was observed when the length
      of the side chain was 3 or 4 carbons. However, the 16 beta-(bromopropyl)
      estradiol easily undergoes cyclization and its effect on 17 beta-HSD is lost.
      Consequently, 16 alpha-(bromopropyl)-E2, 16 alpha-(bromobutyl)-E2, and 16 beta
      (bromobutyl)-E2 were the best inhibitors discussed in this paper.

PMID- 7648201
TI  - Mapping the structural domains of E. coli carbamoyl phosphate synthetase using
      limited proteolysis.
AB  - The structural and functional domains of Escherichia coli carbamoyl phosphate
      synthetase (CPS) have been identified by limited proteolysis. Incubation of CPS
      with several proteases, including trypsin, chymotrypsin, subtilisin and
      endoproteinase Asp-N, under native conditions, causes a time-dependent loss of
      enzymatic activity and the generation of a common fragmentation pattern. Amino
      terminal sequencing studies demonstrated that the initial cleavage event by
      trypsin occurred at the carboxy-terminal end of the large subunit. The ultimate
      fragments produced in most of the proteolysis studies, 35- and 45-kDa peptides,
      were derived from areas corresponding to the putative ATP binding regions.
      Substrate protection studies showed that the addition of ligands did not affect
      the final fragmentation pattern of the protein. However, ornithine and UMP were
      found to significantly reduce the rate of inactivation by inhibition of
      proteolytic cleavage. MgATP and IMP provided modest protection whereas
      bicarbonate and glutamine showed no overall effect on proteolysis. Limited
      proteolysis by endoproteinase Asp-N resulted in the production of a fragment (or
      multiple fragments) which contained enzymatic activity but had lost all
      regulation by the allosteric ligands, UMP and ornithine. The small subunit has
      been shown to be protected from proteolysis by the large subunit. Proteolysis of
      the isolated small subunit resulted in the generation of a stable 31-kDa species
      which contained 10% of the original glutaminase activity. These studies
      demonstrate that a portion of the C-terminal end of the large subunit can be
      excised without entirely destroying the ability of CPS to catalyze the formation
      of carbamoyl phosphate.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7648202
TI  - Structure-activity relationship studies of CNS agents--XVII. Spiro[piperidine
      4',1-(1,2,3,4-tetrahydro-beta-carboline)] as a probe defining the extended
      topographic model of 5-HT1A receptors.
AB  - Spiro[piperidine-4',1-(1,2,3,4-tetrahydro-beta-carboline)] (10), its derivatives
      11-15 and its analogs 16 and 17 were examined as ligands of serotonin 5-HT1A
      receptors. It was shown that compounds 12 and 14 had essentially the same 5-HT1A
      affinity as 1-phenylpiperazine and its rigid analog 7, whereas there were
      substantial differences in the steric arrangement of their crucial
      pharmacophores, i.e. aromatic and protonation centers. On the basis of the
      existing models and using the (+)-LSD structure as a template, a new, extended
      three-point topographic model of 5-HT1A receptors has been proposed.

PMID- 7648203
TI  - A novel series of orally active antiplatelet agents.
AB  - A novel series of orally active fibrinogen receptor antagonists has been
      discovered through structural modification of our lead intravenous (iv)
      antiplatelet agent, 5-(4-amidinophenyl)pentanoyl-Asp-Phe 1 (SC-52012). The Asp
      Phe amide bond was removed through truncation to a 3-substituted beta-amino acid
      aspartate mimetic which resulted in a tripeptide mimetic inhibitor of lower
      molecular weight (from 482 to the 330-390 g mol-1). The zwitterionic nature of
      the inhibitor was masked through the preparation of an ethyl ester prodrug. A
      lead compound from this series, 5-(4-amidinophenyl)pentanoyl-3-(3
      pyridyl)propanoic acid 19a, was found to be a potent inhibitor of canine platelet
      aggregation in vitro (collagen, platelet rich plasma, PRP, IC50 = 270 nM). In
      further canine studies, oral administration of different ester pro-drugs of 19a
      at 10 mg kg-1 resulted in the following oral systemic activities:
      pivaloyloxymethyl ester derivative 19p (5.1 +/- 1.5% OSA), cyclohexyl ester
      derivative 19c (9.2 +/- 1.9% OSA), and ethyl ester derivative 19e (9.9 +/- 2.3%
      OSA).

PMID- 7648204
TI  - HIV protease inhibitor HOE/BAY 793, structure-activity relationships in a series
      of C2-symmetric diols.
AB  - A detailed structure-activity relationship of C2-symmetric diol inhibitors of HIV
      1 protease leads to inhibitor 6 (HOE/BAY 793) which is outstanding in the
      inhibition of the enzyme and in the inhibition of viral replication in HIV
      infected cell culture (IC50: 0.3 nM; EC50: 3 nM). There are well defined steric
      requirements for the design of the side chains P1-P3 of the inhibitors. In
      addition, all three side chains need to be lipophilic. While the enzyme tolerates
      hydrophilic substituents in some cases, drastic reductions in anti-HIV activity
      are observed in cell culture, most likely due to insufficient cell penetration.

PMID- 7648205
TI  - A non-ionic water-soluble pentaphyrin derivative. Synthesis and cytotoxicity.
AB  - The synthesis of the water soluble tetrahydroxypentaphyrin derivative, 1, is
      described. This species, which forms complexes with both small neutral molecules
      and uranyl cation, has been studied as a possible cytotoxic agent. Cytotoxic
      studies performed with the human T lymphoma cell line (JURKAT) revealed that
      pentaphyrin 1 exhibits toxicity at microM concentrations comparable with other
      water soluble, porphyrin-type systems such as the pyridinium metalloporphyrins.

PMID- 7648206
TI  - Time-dependent inhibition of gamma-aminobutyric acid aminotransferase, by 3
      hydroxybenzylhydrazine.
AB  - gamma-Aminobutyric acid (GABA) aminotransferase is a pyridoxal 5'-phosphate (PLP)
      dependent enzyme that catalyzes the conversion of GABA into succinic
      semialdehyde. Hydrazine analogues have long been known to act as inactivators of
      PLP-dependent enzymes, including GABA aminotransferase, however, no studies of
      the molecular mechanism of inactivation of PLP-dependent enzymes by hydrazines
      have been reported. 3-Hydroxybenzylhydrazine is shown to be a potent in vitro
      time-dependent inhibitor of pig brain GABA aminotransferase. UV-visible and 1H
      NMR studies, both with GABA aminotransferase and with PLP as a chemical model for
      the enzyme-catalyzed reaction, indicate that 3-hydroxybenzylhydrazine reacts both
      enzymatically and nonenzymatically to form the 3-hydroxybenzylhydrazone of PLP
      without tautomerization.

PMID- 7648207
TI  - Conformational change due to esterification of hydroxy groups in erythromycin A
      and its major metabolite: analysis of these derivatives with different biological
      properties using NMR and molecular dynamics (MD) data.
AB  - A conformational study is performed on the acylated erythromycin and
      erythralosamine derivatives from comparison between experimental results (NMR)
      and theoretical calculations by Molecular Dynamics (MD) in attempts to correlate
      their conformations with their abilities to generate cytochrome P450-nitroso
      metabolite complexes in vitro. As the 3'-dimethyl-amino function of the
      desosamine is metabolized and responsible for the interaction with cytochrome
      P450, its position, mobility and steric hindrance in the proximity of this
      functional group are related to its biological properties. The major
      conformations of the lactone ring were termed A (A1, A2, A3) and B (B1, B2), and
      this macrocycle flexibility induced five different orientations a, b, c, d and e
      for the desosamine sugar. Conformations A and B differ in many ways but the major
      change is the inward folding of the C(3) fragment in B. Conformer a exhibits an
      orientation of the desosamine nearly perpendicular to the macrocycle whereas the
      two units are in the same plane in conformations c and e. For conformation b, the
      cladinose unit lifts up above the macrocycle. Conformation d exhibits a turned
      back cladinose. In the erythromycin derivatives esterification at the beta
      position to the N(CH3)2 group of the desosamine reduces the degree of freedom of
      the macrocyclic lactone ring which corresponds to conformation A only. The
      desosamine sugar was found to be perpendicular to the macrocycle (a conformer)
      and both sugar groups are parallel to reduce the steric energy. In the
      erythralosamine derivatives, the macrocycle is always present as conformation B
      with the two conformations b and c of the sugar rings. The steric parameters
      favour the b conformers in which the amino group is tilted up, while in 3,2'
      dibenzoylated stacking aromatic attraction stabilizes the planar c conformer.
      Both isomers are thus shown to adopt well-defined conformations and to be well
      adapted for a comparative structure-activity correlation studies. There is a
      significant relationship between the conformation b and the formation of
      cytochrome P450-nitroso metabolite complexes.

PMID- 7648208
TI  - Inhibition of Helicobacter pylori urease by phenyl phosphorodiamidates: mechanism
      of action.
AB  - Helicobacter pylori urease is a nickel-containing enzyme that hydrolyzes urea to
      bicarbonate and ammonia. Andrews et al. (J. Am. Chem. Soc. 1986, 108, 7124) have
      shown that amides and esters of phosphoric acid are slow, tight-binding
      inhibitors of urease isolated from jack bean. We show that 4-substituted phenyl
      phosphorodiamidates (4-R-PhOP(=O)(NH2)2) are slow-binding inhibitors of H. pylori
      urease with no evidence of kinetic saturation. Their second-order rates of
      inhibition ki are strongly correlated with phenol pKa (e.g. R = NO2, ki = 2.5 x
      10(5) M-1s-1; R = OMe, ki = 1.2 x 10(4) M-1s-1). The Bronsted beta for inhibition
      is 0.4, similar to that of model system SN2(P) reactions. Based on these
      observations, we suggest that urease inhibition is covalent but reversible,
      involving a common phosphoacyl enzyme intermediate.

PMID- 7648209
TI  - Analysis of toxicological risks from local contamination by PCDDs and PCDFs:
      importance of isomer distributions and toxic equivalents.
AB  - The concentrations of 2,3,7,8-chlorinated dibenzo-p-dioxins and furans
      (PCDD/PCDFs) at Finnish contaminated sites associated with chlorophenolic (CP)
      wood preservatives were measured by isomer-specific GC/HRMS methods, and the
      implications of the spatial and structural distributions of the isomers and of
      toxic equivalent (TEF) systems for toxicological risks were investigated. High
      concentrations (maximum value of over 90 ppb and arithmetic mean value of 19 ppb
      I-TEQs in dry weight) of PCDD/Fs were found in soil samples from sites where wood
      preservative consisting of 2346-TeCP, PeCP and 246-TCP have been used. The
      PCDD/Fs were distributed heterogeneously between soil layers, the concentrations
      in topsoil samples being generally smaller (mean 9.1 ppb I-TEQ d.w.) than those
      in subsoil (mean 28 ppb I-TEQ d.w.). Concentrations of PCDD/Fs were unrelated to
      the CP contents in the soil samples. Hexa-, hepta- and octachlorinated
      dibenzofurans were the dominant congeners by concentration in these and in most
      other samples, also in the wood preservative. The isomer distribution differed
      considerably between study sites, and even between samples of soil and waste at
      the same site. The relative importance of the samples and isomers was affected by
      the selection of TEFs; the importance of some of the CP-related samples was
      increased when applying TEFs based on lethality to juvenile fish, due to the
      abundance of 123478-HxCDF.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7648210
TI  - PCDD/DFs and coplanar PCBs in sediment and fish samples from the Er-Jen river in
      Taiwan.
AB  - Polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/DFs) and coplanar
      polychlorinated biphenyls (Co-PCBs) have been determined in sediment and fish
      samples from the Er-Jen river in Taiwan. Sediment samples collected near the
      incineration site show TEQ of PCDD/DFs ranging from 14 pg/g to 14200 pg/g and
      2,3,7,8-tetrachlorodibenzo-p-dioxins equivalents (TCDD-EQ) of Co-PCBs ranging
      from 9 pg/g to 1030 pg/g. The fish samples show TEQ of PCDD/DFs ranging from 37
      pg/g to 2084 pg/g and TCDD-EQ of Co-PCBs ranging from 12 pg/g to 120 pg/g.
      Possible PCDD/DFs sources are discharged PCBs, open-air incineration activities,
      and pentachlorophenol. PCB#126 was found to degrade more readily than PCB#77.
      TCDD-EQ of Co-PCBs could be estimated from the total concentration of PCBs. A
      daily intake value of 28 pg/kg/day to 450 pg/kg/day was estimated when consuming
      fish caught from the Er-Jen river.

PMID- 7648211
TI  - Epidemiology and prevention.

PMID- 7648212
TI  - Renal immunology and pathology.

PMID- 7648213
TI  - Determinants of branching tubulogenesis.

PMID- 7648214
TI  - The evolving epidemic of cardiovascular and renal diseases: a worldwide
      challenge.

PMID- 7648215
TI  - The changing focus of hypertension.

PMID- 7648216
TI  - Epidemiology and prevention of diabetic nephropathy.
AB  - Diabetes mellitus is the leading underlying cause of end-stage renal disease in
      the USA. To develop preventive strategies aimed at combatting diabetic end-stage
      renal disease, three steps are required: first, the delineation of the natural
      history of diabetic nephropathy; second, the identification of modifiable risk
      factors for the development and progression of diabetic nephropathy; and third,
      the demonstration that manipulation of these factors does indeed reduce risk. A
      review of the literature regarding the epidemiology and prevention of diabetic
      renal disease in humans published during the past year revealed a wealth of data
      which may guide preventive efforts. Prospective cohort studies confirmed that
      microalbuminuria is a strong predictor of nephropathy and that blood pressure is
      an important modifiable risk factor for the progression of diabetic renal
      disease. In addition, observational studies identified several novel factors
      which might also increase risk. Randomized controlled trials provided convincing
      evidence that strict glycemic control reduces the risk of progression to diabetic
      nephropathy by 50%. Data from trials also demonstrated that angiotensin
      converting enzyme inhibitors slow the progression of renal disease beyond their
      effect on blood pressure alone. Future research should further evaluate novel
      modifiable risk factors, define optimal treatment strategies for the use of
      angiotensin-converting enzyme inhibitors and antihypertensive agents, and develop
      methods to translate these findings into practice for the general population.

PMID- 7648217
TI  - The role of genetic factors in the development of end-stage renal disease.
AB  - Three etiologies of renal disease account for more than 80% of Medicare-supported
      (U.S. Federal Government sponsored) end-stage renal disease (ESRD) cases:
      diabetes mellitus, hypertension and chronic glomerulonephritis. Surprisingly,
      despite improvements in medical care, their incidence is increasing rapidly in
      many parts of the world. With the exception of autosomal dominant adult
      polycystic kidney disease, the DNA polymorphisms causing progressive renal
      failure in individuals with common diseases have not yet been identified.
      Although hypertension and diabetes mellitus are associated with ESRD, the
      majority of patients with these disorders never develop nephropathy. There is
      abundant evidence that both inherited factors and the environment affect the
      development of ESRD. Predisposition to nephropathy may be inherited independently
      from the environmental and hereditary components that produce the associated
      systemic disease. This review examines the evidence that ESRD results, in part,
      from inherited factors. It discusses the racially variable risk of renal disease,
      the familial clustering of ESRD and molecular genetic data in animals and humans
      with renal failure.

PMID- 7648218
TI  - Race and socioeconomic status in hypertension and renal disease.
AB  - Publications within the past year have added to our understanding of the
      relationships between race, socioeconomic status, hypertension, and renal
      disease. The catalog of racial differences in hypertension and renal disease has
      been enriched on several accounts. Some of these differences can be explained by
      specific intervening variables, but others remain attributed to race itself.
      Unfortunately, what 'race' actually represents is still subject to debate. This
      debate should be encouraged, because the lack of a clear concept of race hinders
      research in this area. The main new finding of the year may be a confirmation by
      several studies that low socioeconomic status is an independent risk factor for
      end-stage renal disease, regardless of race. Research explaining the mechanisms
      by which poverty affects the risk of kidney failure is urgently needed, as some
      of these mechanisms may lend themselves to preventive intervention. Interventions
      aimed at improving the serious socioeconomic consequences of treated end-stage
      renal disease are also receiving increasing attention, and have been shown to
      improve patient outcomes.

PMID- 7648219
TI  - Relative benefits of different antihypertensive drugs in the prevention of
      vascular complications.
AB  - Large-scale clinical trials of antihypertensive drugs that have shown a reduction
      in morbidity and mortality used the classic step-care treatment design,
      initiating treatment with a diuretic. Long-term morbidity and mortality reports
      comparing the newer classes of agents with the traditional antihypertensive
      agents have not been completed. A recent meta-analysis of 13 randomized,
      controlled clinical trials of hypertension showed that 18 elderly people, but two
      to four times as many younger people, needed to be treated for 5 years to prevent
      one cerebrovascular or cardiac event. Any head-to-head comparisons of one class
      of antihypertensive agent with another in the prevention of vascular
      complications will require very large cohorts, even of elderly people, to show a
      difference. Such trials are ongoing or being planned, but their results will not
      be available before the next century.

PMID- 7648221
TI  - Death is part of life.

PMID- 7648220
TI  - Exercise in the prevention and treatment of hypertension.
AB  - There is substantial evidence to suggest that regular physical activity reduces
      the risk of heart disease. Less clear is the extent to which this is caused by
      blood pressure reduction. This review considers effects of exercise on blood
      pressure and overall cardiovascular risk in normotensive and hypertensive
      individuals.

PMID- 7648222
TI  - The genetic control of renal development.
AB  - The molecular basis of the organogenesis of the mammalian kidney is being
      investigated at multiple levels, with several exciting developments. Cellular
      signaling during and after kidney induction may be mediated in part by Wnt genes,
      which encode secreted, matrix-associated peptides. The Wilms' tumor suppressor
      gene WT1 is required for the kidney mesenchyme to respond to induction; the
      transcription factor Pax-2 may regulate the aggregation and proliferation of the
      kidney mesenchyme immediately after induction. Although the links between
      signaling molecules, their receptors, and the activation and repression of
      transcription factors in the kidney remain to be determined, several key elements
      of the genetic cascade driving kidney morphogenesis are now characterized.

PMID- 7648223
TI  - Growth factor gene expression in tubular epithelial injury.
AB  - In animal models of acute renal injury, administration of epidermal, insulin-like
      or hepatocyte growth factor accelerates restoration of kidney function and
      normalization of histology, and reduces mortality. Mechanisms for such action
      include stimulation of anabolism, maintenance of glomerular filtration, and
      enhancement of tubular regeneration. Further studies are needed to establish the
      utility of growth factors as therapeutic agents for acute renal failure in
      humans.

PMID- 7648224
TI  - Apoptosis and renal injury.
AB  - Apoptosis or programmed cell death is a major focus of interest in many fields of
      research. Recent advances include definition of key molecules driving the cell
      death programme, including Fas and Fas-ligand in the plasma membrane, and
      cytoplasmic proteases such as interleukin-1 beta-converting enzyme. These are
      kept in check by 'survival' signals conferred by exogenous cytokines and the
      extracellular matrix, or by endogenous proteins encoded by the bcl-2 gene family.
      Important insights into the programme of mammalian cell death have come from
      comparative biology. The scene is now set for study of apoptosis in renal health
      and disease, in which recent studies indicate key roles in remodelling of both
      glomeruli and tubules after renal injury.

PMID- 7648225
TI  - T-cell regulation of renal immune responses.
AB  - Advances in basic immunology have markedly enhanced our understanding of immune
      mediated renal disease, particularly in view of the growing recognition of the
      importance of T-cells in mediating renal injury. Recent milestones in
      investigative technology, including cell-culture techniques supporting T-cell
      clones and renal-derived cell populations, and genetic inbreeding of both
      recombinant and transgenic mice, provide a unique opportunity to study specific
      mechanisms of cell-mediated responses that target the kidney. In the past year
      the role of major histocompatibility complex molecule expression and T-cell
      repertoire selection has been better defined in some models of autoimmune renal
      disease. In addition, new observations regarding mechanisms that downregulate
      injurious T-cell-mediated responses may direct further studies that develop new
      therapeutic modalities.

PMID- 7648226
TI  - The endothelium in glomerular inflammation.
AB  - Endothelial activation is central to the pathophysiology of glomerulonephritis,
      vasculitis, allograft rejection, ischemia-reperfusion injury and thrombotic
      angiopathies. Major advances in endothelial biology during the past year have
      emphasized the importance of selectin, mucin, integrin, and immunoglobulin-like
      adhesion molecules in leukocyte trafficking in glomerular inflammation, and have
      defined novel mechanisms by which leukocyte-endothelial cell interactions are
      regulated by inflammatory mediators and cytokines. These breakthroughs have
      already spawned experimental immunosuppressive strategies that should antecede
      the development of novel, potent and specific therapies for common renal
      diseases.

PMID- 7648227
TI  - Hepatitis C virus-associated glomerulonephritis.
AB  - Hepatitis C virus (HCV) infection is a major cause of chronic liver disease and
      is associated with a variety of extrahepatic manifestations, including
      cryoglobulinemia and glomerulonephritis. Epidemiologic evidence suggests that HCV
      infection may be a major risk factor for both cryoglobulinemic and type I
      membranoproliferative glomerulonephritis (MPGN). Clinical symptoms and laboratory
      data may or may not reflect the presence of chronic liver disease. Most patients
      have evidence of hypocomplementemia, circulating rheumatoid factors, and
      cryoglobulinemia. The pathogenesis of HCV-associated MPGN is probably a result of
      glomerular deposition of circulating HCV and anti-HCV antibodies. Treatment with
      interferon-alpha has been shown to improve proteinuria, suppress viremia, and
      stabilize renal function. However, patients often relapse after therapy is
      stopped. The optimal therapy remains to be defined but may involve different
      dosage regimens of interferon-alpha or the combination of several antiviral
      agents.

PMID- 7648228
TI  - Practice variations, appropriateness and decision analysis.

PMID- 7648229
TI  - Treatment of Helicobacter pylori infections.
AB  - The available literature on the relationship between several diseases and
      Helicobacter pylori (H. pylori) is reviewed. Duodenal ulcer, gastric ulcer,
      complicated peptic ulcer, abdominal symptoms and gastroduodenal mucosal damage
      during the use of non-steroid anti-inflammatory drugs (NSAIDs), non-ulcer
      dyspepsia (NUD) and gastric malignancy are discussed. The case for and against
      eradication is critically discussed. Eradication of H. pylori should be pursued
      in all patients with peptic ulcer disease, whether they are using NSAIDs or not.
      Eradication of H. pylori in the treatment of NUD should be considered
      experimental. Treatment aimed at the eradication of H. pylori should be
      considered in all patients with low-grade malignant mucosa-associated lymphoid
      tissue (MALT) lymphoma and in all patients with Menetrier's disease. Finally,
      this treatment should be considered in a subset of H. pylori-infected patients
      who possibly are at an increased risk of gastric cancer: patients with a strong
      family history of gastric carcinoma and patients in need of long-term treatment
      with a proton-pump inhibitor. In view of the importance of patient compliance,
      the risk of side-effects and the possibility of inducing metronidazole resistance
      when treatment with a metronidazole-containing regimen is used, treatment aimed
      at the eradication of H. pylori should be carefully implemented and monitored.

PMID- 7648230
TI  - Growth hormone deficiency in adults and its response to growth hormone
      replacement.

PMID- 7648231
TI  - Referral for coronary angiography after exercise testing: traditional decision
      making versus decision analysis.
AB  - To audit the referral decisions made by a single cardiologist for coronary
      angiography after exercise testing, we retrospectively reviewed the charts of 303
      consecutive patients in a community hospital. The outcomes of these decisions, in
      terms of angiograms performed and quality-adjusted life expectancy gains as
      predicted by a decision analysis model, were compared with the theoretical
      decisions that would have been made using the model. The 97 patients sent for
      angiography exercised for a shorter time (5.6 +/- 3.1 vs. 6.9 +/- 3.2 min, p <
      0.001) had more ST deviation (2.7 +/- 1.4 vs. 1.7 +/- 1.0 mm, p < 0.001), more
      angina (53.6 vs. 36.9% of patients, p < 0.01) and were more likely to have had a
      previous myocardial infarction (59.8 vs. 33.5% of patients, p < 0.001) than the
      206 not referred. However, of those not referred, 137 were each predicted to gain
      up to 5.7 quality-adjusted life years (QALYs) from bypass surgery. The overall
      predicted gain from the cardiologist's decisions was only 0.1 +/- 2.5
      QALYs/patient. Had the decisions been made using the model, the mean gain would
      have been 1.9 +/- 1.3 QALYs/patient, and an extra 128 patients would have been
      sent for angiography. Decision analysis makes consistent decisions with defined
      risks and benefits. Such decisions can be reproduced, reviewed and analysed,
      whereas traditional decision-making may inconsistently reflect the clinician's
      beliefs and values.

PMID- 7648232
TI  - The natural history and clinical consequences of aspiration in acute stroke.
AB  - Sixty consecutive patients admitted to a teaching hospital with acute stroke were
      studied prospectively for 3 months to define the natural history and consequences
      of lung aspiration. Using videofluoroscopy, aspiration was identified in 25
      patients (42%) within 72 h of stroke onset, and had resolved in all but three
      patients (8%) after 3 months. It was closely related to the presence of
      dysphagia, which itself resolved within 2 weeks in all but the persistent
      aspirators. Lower respiratory tract infection (LRTI) was more common in
      aspirating patients (68%) than non-aspirators (6%). The use of intravenous fluids
      without oral intake did not appear to prevent LRTI in aspirating patients who
      were also dysphagic. Pneumonia occurred after 2 weeks in the three patients
      subsequently found to aspirate persistently. Aspiration is a transient phenomenon
      in most cases of acute stroke; it is associated with a high incidence of LRTI,
      but mortality in this series was not significantly associated either with
      respiratory tract infection or aspiration itself.

PMID- 7648233
TI  - Viridans streptococcal bacteraemia: a clinical survey.
AB  - The occurrence of viridans streptococcal bacteraemia (VSB) in a London
      postgraduate teaching hospital was analysed retrospectively. Over a 30-month
      period, 39 patients with VSB were identified, and the clinical significance of
      VSB was assessed for each, based upon clinical and laboratory information.
      Endocarditis accounted for only 13% of the total patients with apparent VSB. A
      greater proportion of patients with VSB originated from the haematology unit
      (21%) and in particular, the bone-marrow transplantation unit (15%). VSB also
      occurred in patients with solid epithelial malignancies and in children aged < 12
      months. Mortality associated with VSB was 7%. Viridans streptococci are emerging
      as important pathogens in previously unrecognized clinical settings, particularly
      hospitalized, immunocompromised patients.

PMID- 7648235
TI  - Development and preliminary assessment of a simple measure of overall status in
      rheumatoid arthritis (OSRA) for routine clinical use.
AB  - We describe the development and initial assessment of a simple measure of overall
      status in rheumatoid arthritis (OSRA) for use in the routine clinical setting.
      The measure is constructed in four parts: demographic details, activity score,
      damage score and treatment category. It requires no laboratory tests and uses
      details collected routinely during a clinic visit. It was validated in a series
      of 488 patients. The measure proved acceptable and demonstrated face, content,
      construct and discriminant validity. OSRA will be useful as an audit tool in the
      serial follow-up of RA patients and in describing the characteristics of a
      population of such patients.

PMID- 7648234
TI  - Combined bezafibrate and simvastatin treatment for mixed hyperlipidaemia.
AB  - The safety and efficacy of combined bezafibrate-simvastatin therapy was evaluated
      in 49 patients with diet-resistant mixed hyperlipidaemia (type IIb). After a two
      month placebo phase, patients were randomized to receive either Bezafibrate Slow
      Release (SR) 400 mg mane or simvastatin 20 mg nocte followed by three months
      combination therapy. Total cholesterol, triglycerides and high-density
      lipoprotein (HDL) cholesterol were measured at monthly intervals. Apolipoproteins
      (apo) A1 and B, lipoprotein (a) [Lp(a)] and fibrinogen were measured before and
      after each treatment. Simvastatin was more effective than Bezafibrate SR in
      reducing total cholesterol (2.0 vs. 1.1 mmol/l, p = 0.003) and lowering LDL
      cholesterol (1.7 vs. 0.4 mmol/l, p = 0.0001) whereas Bezafibrate SR was more
      effective in reducing triglycerides (by 41% vs. 17%, p = 0.001) and fibrinogen
      (by 23% vs. 3%, p = 0.004). Compared with simvastatin monotherapy, combined drug
      therapy induced further reductions in triglycerides (by 26%, p = 0.0003) and apoB
      (by 11 mg/dl, p = 0.03) and an increase in apoA1 (by 21 mg/dl, p = 0.0008).
      Symptomatic and biochemical adverse events did not occur more frequently on
      combined drug therapy than on monotherapy. The combination of bezafibrate and
      simvastatin was more effective in controlling mixed hyperlipidaemia than either
      drug alone and did not provoke more adverse events.

PMID- 7648237
TI  - Neurasthenia, myalgic encephalitis or cryptogenic chronic fatigue syndrome?

PMID- 7648236
TI  - Reduced awareness of hypoglycaemia in the elderly despite an intact counter
      regulatory response.
AB  - We investigated awareness of hypoglycaemia and its counter-regulatory hormone
      response in six young (ages 24-49, mean 30 years) and seven elderly (ages 65-80,
      mean 72 years) healthy non-diabetic subjects. A hyperinsulinaemic glucose clamp
      was used to control blood glucose level on two separate occasions. During the
      hypoglycaemic study, blood glucose was lowered in a stepwise manner to plateaus
      of 3.5, 3.0 and 2.5 mmol/l. A symptom score, visual reaction time test and digit
      symbol substitution test was completed pre-study, and at the end of each plateau.
      Pulse rate, blood pressure and counter-regulatory hormone measurements were taken
      every 15-30 min. The euglycaemic study was identical except that blood glucose
      remained at the fasting level. During hypoglycaemia, the elderly group had lower
      symptom scores than the young group (total relative score at glucose 2.5 mmol/l,
      mean +/- SEM: elderly -1 +/- 2.5, young 23 +/- 6.7, p < 0.01) and fewer
      individual symptoms despite a similar counter-regulatory hormone response. There
      was no difference in deterioration of the visual reaction times or digit symbol
      substitution scores during hypoglycaemia between the age groups. Unlike the young
      group, the elderly subjects had no tachycardia in response to hypoglycaemia.
      Their reduced awareness of hypoglycaemia may be due to an impaired end-organ
      response to counter-regulatory hormones, resulting in fewer symptoms.

PMID- 7648238
TI  - Pathogenesis of Crohn's disease.

PMID- 7648239
TI  - Lipoprotein (a) and vascular disease: thrombogenesis and atherogenesis.
AB  - Lipoprotein (a) [Lp(a)] has been recognized for nearly 30 years, and
      increasingly, associated with the processes of atherogenesis and thrombogenesis.
      Despite this, the physiological and pathological function (and factors that
      influence levels) of Lp(a) remain largely unknown. Most experimental evidence
      supporting the mechanisms of vascular disease, thrombogenesis and atherogenesis
      have been generated in vitro, and to date, no in vivo confirmation exists. There
      is also a lack of sound evidence for Lp(a) as a risk factor in prospective as
      opposed to case-controlled studies. A fuller understanding of Lp(a) is still
      required in the molecular biology of atherogenesis and thrombogenesis.

PMID- 7648240
TI  - Autosomal recessive erythropoietic protoporphyria: a syndrome of severe
      photosensitivity and liver failure.
AB  - Erythropoietic protoporphyria is caused by inherited deficiency of the haem
      synthetic enzyme ferrochelatase, and is characterized by lifelong
      photosensitivity. About 5% of patients also develop rapidly progressive liver
      failure. Inheritance is considered to be autosomal dominant, with transmission of
      a single ferrochelatase defect from one parent. We describe a family in which two
      siblings with protoporphyria suffered from severe photosensitivity and developed
      hepatic failure requiring liver transplantation. Their asymptomatic parents were
      heterozygous for distinct ferrochelatase gene mutations (exon 10 donor site a(+3)
      ->g and 1088T-->G). Both mutations disrupt splicing of the transcript and cause
      partial deficiency of ferrochelatase. The affected offspring were compound
      heterozygotes for these mutations. These patients suffered from an autosomal
      recessive form of protoporphyria characterized by severe photosensitivity and
      cholestatic liver disease in adolescence. We postulate that hepatic failure in
      erythropoietic protoporphyria may in some cases represent an autosomal recessive
      type of ferrochelatase deficiency distinct from the purely dermatological
      disorder. Studies of disease inheritance in families affected by protoporphyria
      may help identify those predisposed to develop severe liver complications, a
      distinction not currently possible.

PMID- 7648241
TI  - Non-steroidal anti-inflammatory drugs and hospitalization for acute renal
      failure.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) have been implicated in the
      aetiology of acute renal failure (ARF), but epidemiological studies examining
      this association have produced disparate results. We conducted a case-control
      study using a purpose-built record-linkage database for a population of 420,600
      patients, resident in Tayside since May 1990. Patients (n = 207) hospitalized
      with a diagnostic code for ARF between 1990 and 1992 had their diagnosis
      validated by a renal physician. Six community controls and two hospital controls,
      matched for age and sex, were generated for each of these cases. Exposure to
      dispensed oral NSAIDs, topical NSAIDs and aspirin during the 90 days prior to the
      index date were investigated (recent exposure), as was exposure at any time since
      January 1989 (previous exposure). The most significant associations were modelled
      using conditional logistic regression. When community controls were used, recent
      exposure to NSAIDs and previous exposure to aspirin were independently associated
      with hospitalization for ARF, with adjusted odds ratios of 2.20 (1.49-3.25) and
      2.19 (1.46-3.30), respectively. Only recent exposure to oral NSAIDs was
      associated when hospital controls were used: 1.84 (1.14-2.93). No significant
      interactions were present with previous chronic renal failure, other possible
      causes of ARF or whether the diagnosis was primary or secondary. There is an
      approximate doubling of the risk of hospitalization for ARF with use of oral
      NSAIDs.

PMID- 7648242
TI  - Laparoscopy and histology in the diagnosis of chronic liver disease.
AB  - We compared laparoscopy with histology in identifying fatty change, fibrosis, the
      degree of inflammatory activity, cirrhosis and the cause of liver disease.
      Laparoscopic liver biopsy was performed in 145 consecutive patients. The
      laparoscopist and the histologist were provided with similar clinical and
      biochemical information. Both scored the appearances on respective examinations
      for the degree of fatty change, fibrosis and activity, presence or absence of
      cirrhosis; and provided a provisional diagnosis. The final diagnosis was
      determined by clinicopathological conference and clinical follow-up. Laparoscopy
      was successfully performed in 142 patients (97.9%). Compared with histology, the
      sensitivity and specificity of laparoscopy for identifying fatty change were
      96.4% and 100%, 100% and 95% for fibrosis and 94% and 95% for inflammatory
      activity, respectively. For cirrhosis, laparoscopy was 100% sensitive and 97.1%
      specific. Histology missed 10 cases of cirrhosis (6.1%). Histology did, however,
      provide additional information in 9 patients (6.3%) which contributed to the
      final diagnosis. Overall, histology is required in addition to laparoscopy in
      cases where the aetiology is unclear. The sensitivity and specificity in
      identifying fatty change, fibrosis, activity and cirrhosis are similar for
      laparoscopy and histology. The combination of information gained on laparoscopy
      with histology provides the diagnosis in most patients. Laparoscopy may replace
      the need for liver biopsy in patients in whom the aetiological diagnosis is not
      in question and the biopsy is being performed to stage the disease. We used it as
      an integral part of the work-up of a patient with liver disease.

PMID- 7648243
TI  - A double-blind comparison of bisoprolol and atenolol in patients with essential
      hypertension.
AB  - We compared the beta 1-selective adrenoceptor antagonists bisoprolol and atenolol
      in a double-blind, randomized crossover study. After 4 weeks placebo phase, 59
      patients with essential hypertension received either 10 mg bisoprolol or 50 mg
      atenolol once daily for 8 weeks, increased if necessary (target BP < or = 150/90
      mmHg) to 20 and 100 mg, respectively, after 4 weeks. After a second placebo
      phase, crossover occurred to the alternative drug. We measured resting systolic
      and diastolic blood pressures and heart rate at 24 h post-dose baseline and after
      4 and 8 weeks treatment. Both drugs significantly lowered systolic and diastolic
      blood pressures and heart rate at 8 weeks compared to baseline (all p < 0.05).
      Bisoprolol reduced heart rate significantly more than atenolol (p < 0.01), but
      systolic and diastolic blood pressure changes were not different between the two
      drugs. There was no difference in patient acceptability of the drugs as assessed
      by visual analogue scale. Despite theoretical and circumstantial evidence to
      suggest superiority of bisoprolol over atenolol, no significant difference
      between the two was found except for greater heart rate reduction with
      bisoprolol.

PMID- 7648244
TI  - Peripartum hypopituitarism and lymphocytic hypophysitis.
AB  - The classical cause of postpartum hypopituitarism is Sheehan's syndrome, in which
      an obstetric catastrophe is associated with hypotension. However, with
      improvements in obstetric care, the most common cause now may be lymphocytic
      hypophysitis. Five women with postpartum hypopituitarism, whose symptoms occurred
      during or immediately after pregnancy, had detailed endocrine and pituitary
      imaging for the duration of follow-up. Two presented with visual symptoms, and
      three with non-specific illnesses related to varying deficiencies of anterior
      pituitary hormones. Four were unable to lactate, and four were initially
      amenorrhoeic. Initially, four of the five women had enlarged pituitary glands on
      magnetic resonance imaging. Four have to some extent recovered pituitary
      function. One patient had associated thyroiditis: in two cases antinuclear
      antibodies became positive during follow-up, and in one of these dsDNA antibody
      was also detected. In no case were pituitary antibodies detected. None had
      complicated pregnancies or deliveries, and the two who had caesarean sections had
      no episodes of hypotension. The presentation of secondary hypothyroidism combined
      with ACTH deficiency in four of the five women strongly suggests lymphocytic
      hypophysitis. This diagnosis should be considered in postpartum women with
      general malaise and persistent amenorrhoea, as well as in women who develop
      visual impairment in the last trimester of pregnancy without antecedent pituitary
      disease. A conservative policy of management of the pituitary enlargement should
      be pursued as this resolves.

PMID- 7648246
TI  - Gender bias in treatment for coronary heart disease: fact or fallacy?

PMID- 7648245
TI  - Idiopathic eosinophilic myositis.
AB  - Eosinophilic myositis is a rare entity accompanying parasitic infection or other
      inflammatory disorders. Two cases are reported in which myalgia and eosinophilic
      infiltration of muscle occurred in the absence of associated disease, and twelve
      previously published cases of idiopathic eosinophilic myositis are reviewed. A
      classification system for idiopathic eosinophilic muscle disease is proposed,
      describing three distinct groups. Comparisons are drawn between these and other
      causes of eosinophilic muscle disease, outlining the differential diagnoses for
      each group.

PMID- 7648247
TI  - Agrammatic sentence production: the use of a temporal--spatial strategy.
AB  - We report the sentence production of a left-handed man with a right-hemisphere
      infarct. He demonstrated an inability to correctly map grammatical categories
      (subject, object) onto thematic roles (agent, patient) even for simple active
      sentences. The patient's performance appears to be the result of selective damage
      to the functional level (Garrett, 1980) of sentence production. His failure could
      not be accounted for by theories of agrammatism that implicate memory deficits,
      phonologic processing impairments, or deficits in processing complex
      transformations. The patient's performance revealed the consistent application of
      a temporal-spatial strategy in sentence production, despite adequate lexical
      semantic abilities.

PMID- 7648248
TI  - Asyntactic thematic role assignment: the use of a temporal-spatial strategy.
AB  - We report syntactic comprehension performance of a left-handed man with a right
      hemisphere infarct. He was unable to accurately map grammatical categories
      (subject, object) onto thematic roles (agent, patient), despite demonstrating
      intact conceptual knowledge of these thematic roles. He performed poorly on both
      active and passive reversible sentences. His asyntactic thematic role assignment
      cannot be accounted for by a short-term memory impairment or any hypothesis that
      predicts selective vulnerability to passive sentence constructions. Rather than
      performing randomly, our patient used a temporal or spatial strategy in assigning
      thematic roles. Because he also had a production-mapping deficit and used the
      same temporal-spatial strategy in production tasks, we hypothesize that the
      mapping of thematic roles onto grammatical categories and vice versa may be a
      specific aspect of sentence processing that is common to sentential production
      and comprehension. We also raise the possibility that thematic roles have
      underlying spatial representations prior to being elaborated by grammar.

PMID- 7648249
TI  - EEG power spectra of dysphonetic and nondysphonetic poor readers.
AB  - Two subtypes of poor readers, dysphonetic and phonetic, were compared on EEG
      spectral values obtained as they viewed strings of letters and short words.
      Dysphonetic poor readers had significantly higher values than phonetics in the
      theta and delta bands. Both phonetic and dysphonetic poor readers had lower beta
      values than adequate reading children with Attention Deficit Disorder. This
      evidence indicates that poor readers, especially dysphonetics, were less actively
      engaged in the task.

PMID- 7648250
TI  - The production of semantic paralexias in a Spanish-speaking aphasic.
AB  - A case of a Spanish-speaking aphasic patient who produced a great number of
      semantic paralexias in reading aloud and who showed other symptoms consistent
      with the diagnosis of deep dyslexia is presented. In this study, (a) the
      production of semantic paralexias and the features of the deep dyslexia syndrome
      which have only recently begun to be studied in Spanish-speaking patients, are
      analyzed; and (b) the "obligatory character of phonological mediation in the
      reading of Spanish proposed by some authors is discussed.

PMID- 7648251
TI  - Another sighting of differential language laterality in multilinguals, this time
      in Loch Tok Pisin: comments on Wuillemin, Richardson, and Lynch (1994).
AB  - Wuillemin, Richardson, and Lynch (1994) claim to have determined that languages
      learned after the age of 8 are less lateralized than those learned earlier. The
      authors fail to specify the nature of what it is that is differentially
      lateralized. It cannot be implicit linguistic competence (the language system),
      since that has been clinically demonstrated to be false. It cannot be pragmatic
      and paralinguistic aspects of language use, since, to the extent that these are
      right-hemisphere based functions, they could not be reflected in results obtained
      with a technique assumed to selectively tap left-hemisphere functions. Either
      way, the visual half-field technique used proves to be an invalid measure of
      language laterality in individuals or subgroups.

PMID- 7648252
TI  - Immunohistochemical localization of the low molecular weight stress protein HSP27
      following focal cerebral ischemia in the rat.
AB  - We immunohistochemically investigated the induction and localization of a low
      molecular weight stress protein, HSP27, in the rat brain following 1 hr of middle
      cerebral artery occlusion in comparison with those of HSP70. The brains were
      perfusion-fixed after 4 h, 1 day, 3 days, 7 days, and 14 days of reperfusion.
      Frozen sections were then prepared and used for immunohistochemistry. In normal
      brains, we observed no immunoreactivities to HSP70 and HSP27. HSP70 was localized
      predominantly in neurons in areas peripheral to the ischemic center after 1 day
      and 3 days, and in endothelial cells and perivascular cells within the ischemic
      center after 1 day. In contrast, HSP27 was induced in microglia in the ischemic
      center after 4 h, and then in reactive astrocytes distributed widely in the
      ipsilateral hemisphere and in part of the contralateral hemisphere after 1
      through 14 days. In the center of ischemia where infarction developed, only
      nonspecific staining was seen. Thus, the expression patterns of HSP70 and HSP27
      were quite different with regard to cell type, distribution, and time course
      following focal cerebral ischemia. HSP70 may be a sensitive marker of acute
      neuronal stress in the penumbral areas, whereas HSP27, which was most prominently
      induced in reactive astrocytes in periischemic and remote areas, may be a
      component of glial reaction to injury.

PMID- 7648253
TI  - In vivo imaging of brain incorporation of fatty acids and of 2-deoxy-D-glucose
      demonstrates functional and structural neuroplastic effects of chronic unilateral
      visual deprivation in rats.
AB  - Regional cerebral 'incorporation coefficients' k* of each of 3 labeled long-chain
      fatty acids -[9,10-3H]palmitate ([3H]PA), [1-14C]arachidonate ([14C]AA) and [1
      14C]docosahexaenoate ([14C]DHA)-were measured using quantitative autoradiography
      in 11 bilateral brain visual areas of 3.5-month-old awake, hooded, Long-Evans
      rats, and were compared with regional cerebral metabolic rates for glucose
      (rCMRglc). The rats, which had undergone unilateral orbital enucleation at 15
      days of age, were studied either in the dark with eyelids of the intact eye
      sutured, or when stimulated in a light box with the intact eye open. rCMRglc did
      not differ between homologous contralateral and ipsilateral visual areas in the
      dark or during stimulation, but was elevated bilaterally by 25% or more in many
      visual areas during stimulation compared with dark. Contralateral compared with
      ipsilateral k* was lower for each fatty acid tracer in superficial gray of the
      superior colliculus (in dark and during stimulation) and dorsal nucleus of
      lateral geniculate body (during stimulation). In the dark, k* for [3H]PA was
      correlated significantly with rCMRglc for the 22 visual areas studied, whereas
      during stimulation k* for [14C]AA was correlated with rCMRglc. These results
      suggest that central neuroplastic changes following chronic unilateral
      enucleation are accompanied by reduced incorporation of [3H]PA, [14C]AA and
      [14C]DHA into contralateral brain ares that normally receive crossed retinofugal
      fibers, and by symmetry of rCMRglc in the dark but increased bilateral
      symmetrical responsiveness of rCMRglc to visual stimulation of the intact eye.

PMID- 7648254
TI  - The thalamic reticular nucleus does not send commissural projection to the
      contralateral parafascicular nucleus in the rat.
AB  - The reticular nucleus of the thalamus (NRT) projects to virtually all thalamic
      nuclei ipsilaterally. In addition, recent studies suggest that NRT sends
      contralateral projections through an intrathalamic commissural fiber system to
      several thalamic nuclei, including the NRT itself. In the present study we used
      retrograde cell labeling, multi-unit anterograde labeling and immunohistochemical
      methods to study both ipsi- and contralateral NRT projection to the
      parafascicular nucleus (Pf) in the rat. Injections of the fluorescent tracers
      true blue or fluorogold in Pf led to massive retrograde cell labeling in rostral
      and dorsal portions of the ipsilateral NRT, whereas the same sectors of the
      contralateral NRT were devoid of labeling. Some retrogradely labeled cells were
      nevertheless present on the contralateral side in the borderline region between
      NRT and the zona incerta (ZI). Retrograde cell labeling experiments with cholera
      toxin B subunit (CTb) combined to immunohistochemistry for parvalbumin (PV) and
      calbindin D-28k (CB) indicated that the few retrogradely labeled cells
      encountered at the border between NRT and ZI displayed immunoreactivity for CB
      but not for PV. Since PV and CB label neurons belonging to NRT and ZI,
      respectively, it is concluded that these contralateral retrogradely labeled cells
      belong to ZI and not to NRT. Multi-unit cell anterograde labeling experiments
      with biocytin showed that NRT cells that project to Pf arborize extensively only
      on the ipsilateral side. The same approach, however, has revealed NRT cells
      projecting to both ipsi- and contralateral ventromedial thalamic nuclei. The axon
      of these NRT neurons arborizes more profusely ipsilaterally than contralaterally.
      These results reveal that the NRT projection to Pf in rodents is strictly
      unilateral. These findings are at variance with the emerging concept that NRT
      exerts a prominent bilateral influence upon most thalamic nuclei.

PMID- 7648255
TI  - Effect of rapid correction of hyponatremia on the blood-brain barrier of rats.
AB  - Brain demyelination sometimes follows rapid correction of hyponatremia,
      especially if the hyponatremia is chronic. During correction brain water
      decreases and the brain shrinks. The present study examined whether such
      shrinkage might be sufficient to disrupt the tight junctions of the blood-brain
      barrier. Barrier intactness was evaluated using magnetic resonance imaging and
      intravenous gadolinium contrast administration. Hypertonic saline infusion
      rapidly increased the plasma sodium concentration and caused barrier disruption
      more frequently in chronic than in acute hyponatremic rats. Similar increases in
      plasma sodium concentration did not disrupt the barrier in normonatremic rats.
      The disruption appeared to be due to altered plasma osmolality since infusion of
      hypertonic mannitol, which raised plasma osmolality without changing the plasma
      sodium concentration, disrupted the barrier in hyponatremic but not normonatremic
      rats. Moreover, the osmotic threshold for barrier disruption was lowest in
      chronic hyponatremia, intermediate in acute hyponatremia, and highest in
      normonatremia. The greater susceptibility to osmotic disruption in chronic
      hyponatremia suggests that blood-brain barrier disruption may play a significant
      role in causing the demyelination sometimes found following too rapid correction
      of hyponatremia, possibly through exposure of oligodendrocytes to plasma
      macromolecules such as complement.

PMID- 7648256
TI  - Changes in TRH and its degrading enzyme pyroglutamyl peptidase II, during the
      development of amygdaloid kindling.
AB  - Pyroglutamyl peptidase II (PPII) is a neuronal ectoenzyme responsible for
      thyrotropin releasing hormone (TRH) degradation at the synaptic cleft. PPII,
      heterogeneously distributed in different brain regions and adenohypophysis, is
      regulated under various endocrine conditions where TRH is involved in thyrotropin
      or prolactin regulation but only at the adenohypophyseal level. TRH can
      downregulate PPII activity in cultured adenohypophyseal cells. TRH present in
      extrahypothalamic brain areas has been postulated to serve as a neuromodulator
      and levels of this peptide increase in amygdala, hippocampus and cortex after
      electrical stimulation (kindling or electroshock). To study whether brain PPII
      could be regulated in conditions that stimulate TRHergic neurons, TRH and PPII
      activity were determined during the development of amygdaloid kindling in the
      rat. TRH levels increased from stage II to V in amygdala and hippocampus in the
      ipsi- and contralateral side to stimulation. In n. accumbens a decrease, compared
      to sham was observed at stage II, but levels raised through stage V. In contrast,
      PPII activity was increased at stage II, in amygdala of both sides and in
      hipppocampus, frontal cortex, n. accumbens and hypothalamus of the contralateral
      side; levels decreased at stage V to sham values in most structures (except
      amygdala and hippocampus where the activity was 30% below controls). These
      results suggest that PPII activity in the central nervous system can be regulated
      in conditions known to affect TRHergic neurons.

PMID- 7648257
TI  - Search for novel ligands selective at a polyamine recognition domain on the N
      methyl-D-aspartate receptor complex using membrane binding techniques.
AB  - Among over 60 polyamine derivatives tested, only N-(3-aminopropyl)octanediamine
      and bis-(3-aminopropyl)nonanediamine (TE393) markedly inhibited [3H](+)-5-methyl
      10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imi ne (MK-801) binding at
      equilibrium in the presence of added spermidine (SPD) in "non-washed" rat brain
      synaptic membranes, without affecting that in the absence of added SPD. Although
      TE393 significantly potentiated [3H]MK-801 binding before equilibrium in the
      presence of L-glutamic acid (Glu) alone or both Glu and glycine (Gly) added in
      "Triton-treated" membranes, the putative polyamine antagonists 1,10-decanediamine
      (DA10) and arcaine invariably inhibited binding irrespective of the addition of
      agonists. In the absence of added SPD, in addition, TE393 markedly enhanced
      abilities of both Glu and Gly to potentiate [3H]MK-801 binding before
      equilibrium. However, TE393 induced a rightward shift of the concentration
      response curve of SPD for [3H]MK-801 binding before equilibrium. Moreover, TE393
      was effective in potentiating binding of an antagonist but not an agonist
      radioligand to the NMDA domain and in inhibiting binding of an antagonist but not
      an agonist radioligand to the Gly domain. The potentiation of NMDA antagonist
      binding by TE393 occurred in a manner sensitive to prevention by arcaine but not
      by DA10. These results suggest that TE393 may be a novel ligand at the polyamine
      domain with an ability to interact with both the NMDA and Gly recognition domains
      in antagonist-preferring forms.

PMID- 7648259
TI  - A single (-)-nicotine injection causes change with a time delay in the affinity
      of striatal D2 receptors for antagonist, but not for agonist, nor in the D2
      receptor mRNA levels in the rat substantia nigra.
AB  - The in vitro and in vivo effects of (-)-nicotine on dopamine D2 receptors in the
      rat neostriatum have been studied using biochemical binding, in situ
      hybridization and immunocytochemistry. A single i.p. injection (1 mg/kg) of (-)
      nicotine resulted in a reduction of the KD value of the D2 antagonist
      [3H]raclopride binding sites in rat neostriatal membrane preparations at 12 h
      without any significant change in the Bmax value. This action of (-)-nicotine was
      counteracted by pretreatment 15 min earlier with the nicotine antagonist
      mecamylamine (1 mg/kg, i.p.). However, the KD and the Bmax values of the D2
      agonist [3H]NPA binding sites in the rat neostriatal membrane preparations were
      not significantly affected 0.5-48 h after a single i.p. injection with 1 mg/kg of
      (-)-nicotine. No significant change in neostriatal D2 receptor mRNA levels was
      observed at any time interval after the (-)-nicotine injection. No significant
      change was observed in tyrosine hydroxylase (TH) immunoreactivity in either the
      substantia nigra or the neostriatum, nor in nigral TH mRNA levels during the time
      interval studied (4-24 h posttreatment). Furthermore, addition of low (10 nM) or
      high (1 microM) concentrations of (-)-nicotine in vitro to rat neostriatal
      membranes did not alter the characteristics of [3H]raclopride or [3H]NPA binding.
      These results indicate that a single (-)-nicotine injection can produce a
      selective and delayed increase in the affinity of D2 receptors for the
      antagonist, but not for the agonist without modifying the levels of D2 receptor
      mRNA, probably via the activation of central nicotinic receptors.

PMID- 7648258
TI  - Amyloid beta protein 1-42/43 (A beta 1-42/43) in cerebellar diffuse plaques:
      enzyme-linked immunosorbent assay and immunocytochemical study.
AB  - Diffuse plaques are immature and amorphous senile plaques and believed to be in
      the initial phase of plaque formation. In contrast to amyloid angiopathy and the
      plaque core amyloid, diffuse plaques failed to be purified in preserved forms
      from the brain. Here, we studied the diffuse plaques in the cerebellar region of
      the Alzheimer's disease brain based on immunocytochemistry and ELISA using two
      different monoclonal antibodies specifically recognizing the carboxyl termini of
      A beta molecules (BA27 for A beta 1-40 and BC05 for A beta 1-42/43). We found
      that the amount of A beta 1-40 was in proportion to the staining degree on
      amyloid angiopathy by immunohistochemistry. We found that A beta 1-42/43
      comprised diffuse plaques as the major component in the cerebella of AD brains.
      Taking these findings into consideration, diffuse plaques, the earliest
      pathological change in the brain with AD, are concluded to be composed mainly of
      A beta 1-42/43, implicating the critical importance of this kind of A beta
      species deposition in the pathogenesis of AD.

PMID- 7648260
TI  - Evidence for a differential modulation of the alpha-2 adrenoceptors by
      angiotensin II in the nucleus tractus solitarii of the spontaneously hypertensive
      and the Wistar-Kyoto normotensive rats.
AB  - An interaction between angiotensin II (Ang II) receptors and alpha 2
      adrenoceptors was evaluated in the nucleus tractus solitarii (NTS) of the
      normotensive Wistar-Kyoto rat (WKY) and of the spontaneously hypertensive rat
      (SHR) using quantitative receptor autoradiography and cardiovascular analysis. In
      the WKY rat, Ang II promoted a dose-dependent increase in the IC50 value of l
      noradrenaline when competing for ([3H]p-aminoclonidine ([3H]PAC) binding sites,
      which reached a maximum of 400% with 10 nM of Ang II and was associated with a
      small decrease in the B0 value (20%). In the SHR Ang II (0.1 nM) had an opposite
      effect leading to a decrease in the IC50 value of about 57%, and no change was
      observed in the B0 value. Saturation analysis also showed that Ang II (0.1 nM)
      increased the KD value of [3H]PAC in the WKY strain but in contrast decreased the
      KD value of [3H]PAC in the SHR. The Bmax value was not significantly changed
      neither in the WKY rat nor in the SHR. The cardiovascular analysis showed that a
      threshold dose of Ang II (0.05 pmol) counteracted the vasodepressor effect
      produced by l-noradrenaline coinjected in the NTS of the WKY rat. No effect was
      observed in heart rate. In the SHR no counteraction of the l-noradrenaline
      induced vasodepressor effect was found, and in contrast a slight increase of the
      vasodepressor effect associated with a significant increase in the bradycardiac
      response was observed. The results give evidence for an antagonistic Ang II/alpha
      2 receptor interaction in the cardiovascular part of the NTS of the WKY rat as
      previously observed in the Sprague-Dawley rat. However, this interaction is
      altered in the SHR, so that in this strain the Ang II/alpha 2 receptor
      interaction enhances alpha 2 affinity and possibly alpha 2 receptor function.
      This opposite effect observed in the SHR may represent one compensatory mechanism
      to counteract the development of high blood pressure in the SHR.

PMID- 7648261
TI  - Regulation of alternative splicing in the amyloid precursor protein (APP) mRNA
      during neuronal and glial differentiation of P19 embryonal carcinoma cells.
AB  - Cell-specific alteration in the splicing of exons 7, 8 and 15 of the amyloid
      precursor protein gene was investigated in differenting P19 EC cells into
      neuronal and glial cells. Exons 7 and 8 were skipped in the neuronal state and
      exon 15 was skipped in the glial state. Expression of U2AF, one of the essential
      factor for splicing in mammalian cells, was down-regulated during cellular
      differentiation. The skipping of exon 15 was suppressed in the glial cells
      transfected with U2AF. Thus, a reduction in U2AF is believed to play a crucial
      role in glial-specific splicing of the APP gene.

PMID- 7648262
TI  - Involvement of NMDA receptors in inspiratory termination in rodents: effects of
      wakefulness.
AB  - We investigated the role of N-methyl-D-aspartate (NMDA) receptors in the off
      switching of inspiration in rodents. Respiratory activity was measured by the
      plethysmographic method in Swiss and Balb c mice, Hartley guinea pigs, Wistar and
      Sprague-Dawley rats. The NMDA channel blocker dizocilpine (MK-801) administered
      systemically, had little effect on the timing of respiratory phases in intact
      animals. When dizocilpine was associated with a vagotomy performed under
      anesthesia, an apneustic respiratory pattern was obtained in all species and
      strains. As the anesthetic dissipated, the inspiratory pauses disappeared and the
      apneustic respiratory pattern was replaced by an eupneic respiratory pattern.
      Apneuses were re-instated by small doses of anesthetic (halothane, pentobarbital,
      alphaxolone-alphadolone or chloral hydrate) and suppressed by larger doses. We
      conclude that (i) the central NMDA-receptor dependent inspiratory off-switching
      mechanism previously described in cats and primates, also exists in rodents; (ii)
      wakefulness maintains a normal respiratory pattern after suppression of both the
      NMDA-receptor mediated and the vagally-mediated off-switching mechanisms; (iii)
      deep anesthesia suppresses inspiratory pauses in rodents.

PMID- 7648263
TI  - Sodium depletion induces Fos immunoreactivity in circumventricular organs of the
      lamina terminalis.
AB  - Acute sodium depletion by peritoneal dialysis (PD) induces c-fos expression in
      the subfornical organ (SFO) and organum vasculosum laminae terminalis (OVLT), in
      conscious rats. Fos immunoreactive (Fos-ir) neurons detected by
      immunohistochemistry first appeared in these nuclei 60 min after PD, increased
      gradually in the next 4 h and remained high for 27 h following PD. Fos-ir cells
      were distributed throughout the body of SFO, being the core of the posterior
      sections preferentially activated, whereas Fos-ir neurons occurred around the
      periphery of OVLT (annular disposition). When rats were allowed to drink sodium
      salt (1.8% NaCl) 24 h after PD, there was a marked reversion of the c-fos
      expression in the OVLT and a comparatively smaller effect in the SFO.
      Intracerebroventricular infusion of hypertonic CSF (170 mM NaCl) from 30 min
      before and during 4 h after PD, significantly inhibited the c-fos expression in
      both nuclei. These results demonstrate that an acute body sodium deficit induces
      c-fos activity in SFO and OVLT neurons, indicating the special role of these
      structures in sodium balance regulation. They also show that the sodium-depletion
      induced production of Fos in neurons of the lamina terminalis can be modulated by
      central or systemic reposition of sodium.

PMID- 7648264
TI  - Gut bacteria provide precursors of benzodiazepine receptor ligands in a rat model
      of hepatic encephalopathy.
AB  - Benzodiazepine receptor (BZR) ligands are elevated in animals and humans with
      fulminant hepatic failure (FHF) and contribute to the pathogenesis of the
      associated hepatic encephalopathy (HE). As gut factors are proposed to play a
      role in the pathogenesis of HE, we investigated gut flora as a source of BZR
      ligands. Rats received daily oral neomycin, vancomycin and metronidazole (AB +)
      or saline (AB -) before and concurrent with the induction of FHF with
      thioacetamide. BZR ligands were extracted from brain and plasma and quantified
      using radiometric techniques. Plasma BZR ligand concentrations in AB(+) and AB(-)
      rats with HE were higher than AB(+) and AB(-) control rats. Brain BZR ligand
      concentrations increased in AB(+) and AB(-) rats with HE. Stool cultures from
      antibiotic treated rats with HE indicated the presence of multidrug resistant
      Acinetobacter lwoffii. Although no significant concentrations of BZR ligands were
      detected in culture media inoculated with A. lwoffii, administering A. lwoffii to
      normal rats significantly elevated BZR ligand levels in brain, but not plasma.
      Thus, antibiotic treatment of rats is associated with the growth of a resistant
      strain of bacterium which produces an inactive BZR ligand precursor. BZR ligands
      may be synthesized from these precursors in the brain and efficiently cleared by
      a normal liver following brain-to-plasma transfer. Impairment of this clearance
      process in FHF facilitates their accumulation, enabling agonist BZR ligands to
      contribute to the pathogenesis of HE by further enhancing GABAergic
      neurotransmission.

PMID- 7648265
TI  - Effects of decentralization on the levels of GAP-43 and p38 (synaptophysin) in
      sympathetic adrenergic neurons: a semi-quantitative study using
      immunofluorescence and confocal laser scanning microscopy.
AB  - The distribution of GAP-43 in superior cervical ganglion (SCG) and iris were
      studied in normal animals and following decentralization using immunofluorescence
      and confocal laser scanning microscopy (CLSM). GAP-43-like immunoreactivity (LI)
      was compared with p38 (synaptophysin)-LI, and tyrosin hydroxylase (TH)-LI. In the
      control SCG, GAP-43-LI and p38-LI were mainly localized in nerve terminals around
      the principal neurons. The neuronal perikarya were negative for GAP-43, but
      positive for p38 in a perinuclear zone, as well as positive for TH. SIF cells
      (Small Intensely Fluorescent cells, ganglionic interneurons) were positive for
      GAP-43, TH and p38. One day after decentralization, GAP-43-LI and p38-LI in nerve
      terminals around principal neurons had disappeared. Some of the principal neurons
      showed a weak GAP-43-immunoreactivity. Three days post-decentralization, GAP-43-
      and p38-positive nerve terminals around the neurons had reappeared in
      considerable numbers and the intra-ganglionic nerve bundles were positive for
      both antibodies. In the control irides, GAP-43-LI and p38-LI were distributed in
      a varicose pattern in the nerve bundles, around blood vessels and in the network
      of terminals. Double labelling studies showed that GAP-43-LI was colocalized with
      TH-LI and p38-LI. The network of terminals in the dilator plate of the irides was
      quantified by measuring the fluorescence intensity of randomly selected areas,
      using CLSM. Three days after decentralization the intensity of GAP-43-LI and p38
      LI had significantly increased. TH-LI had decreased 8 days after
      decentralization. The results indicate that GAP-43-LI and p38-LI are normally
      present in the nerve fibers and terminals of both pre- and post-ganglionic
      neurons in adult rats. The expression of GAP-43-LI and p38-LI in post-ganglionic
      neurons is preganglionically regulated, as indicated by the increased expression
      after decentralization. The expression of p38 in these neurons is probably
      regulated via mechanisms that are separate from those which regulate GAP-43,
      since it showed a different time course than that of GAP-43-LI.

PMID- 7648266
TI  - Anabolic-androgenic steroid and adrenal steroid effects on hippocampal
      plasticity.
AB  - Anabolic-androgenic steroids (AAS) are synthetic androgen-like compounds which
      are taken in high doses by athletes with the intention of enhancing muscular
      appearance, strength and/or athletic performance. Recent research indicates that
      high doses of AAS may influence the functions of the hippocampus. This evidence
      led us to explore the extent to which chronic AAS treatments influence spatial
      memory and the integrity of the hippocampus in the rat. Gonadally intact adult
      male Long-Evans rats were treated with either the AAS methandrostenolone, a
      steroid 'cocktail' (TNB; testosterone cypionate, boldenone undecylenate and
      nandrolone decanoate), or the oil vehicle daily for 12 weeks. A group of male
      rats treated with corticosterone (CORT; 10 mg/day) was also examined. Spatial
      memory was assessed in the Morris water maze after 10 weeks of hormone treatment.
      At 12 weeks, the animals were sacrificed, blood collected and the brain sectioned
      to assess hippocampal cell number. There were no impairments in the acquisition
      or retention of the Morris water maze in any hormone treatment group. Although
      serum testosterone levels were elevated in rats treated with TNB relative to the
      oil controls, neither the TNB or methandrostenolone treatments produced changes
      in hippocampal cell number. Serum CORT levels were significantly elevated in the
      rats treated with CORT and cell loss (15%) was detectable in the CA3b subfield in
      this group of animals. These results indicate that the AAS administered in the
      present study were not detrimental to hippocampal spatial memory or cell survival
      and that, while chronic CORT may produce mild hippocampal cell loss, this loss is
      not accompanied by deficits on a spatial memory task.

PMID- 7648267
TI  - Glucocorticoid receptor mRNA in Alzheimer's diseased hippocampus.
AB  - Hypothalamic-pituitary-adrenal (HPA) axis dysfunction is a common finding in
      Alzheimer's dementia. Since there is a loss of hippocampal corticosteroid
      receptors in animal models of aging, and since hippocampal cell loss occurs in
      Alzheimer's disease (AD), it has been suggested that a loss of hippocampal
      glucocorticoid receptors (GR) may underlie some aspects of HPA axis dysfunction
      in patients with AD. Levels of corticosteroid receptor protein are not reliably
      determined in postmortem human brain due to rapid lability. In contrast, levels
      of mRNA coding for GR are stable in postmortem tissue. We report here initial
      observations from in situ hybridization experiments which indicate that regional
      levels of glucocorticoid receptor mRNA in hippocampus, as determined by film
      autoradiography, are significantly higher in AD hippocampus than in controls.
      While neuronal levels of GR mRNA in AD, revealed by emulsion autoradiography,
      were equal in control and AD tissue. Taken together these results suggest that
      adrenal dysfunction in AD may relate to defects in receptor function rather than
      corticosteroid receptor loss in the hippocampus.

PMID- 7648268
TI  - Cloning and characterization of the promoter region of the mouse mu opioid
      receptor gene.
AB  - Opioid compounds have potent analgesic and euphoric properties. They act with
      specific cell-membrane receptors which have been pharmacologically defined into
      three major classes, mu, kappa and delta. These receptors are highly regulated
      with respect to their gene expression, resulting in a temporally and spatially
      specific pattern of distribution for each receptor. To characterize the promoter
      sequence of the mu opioid receptor (MOR) gene, a mouse genomic DNA library was
      screened under high stringency with a rat MOR (MOR-1) cDNA probe and genomic
      sequences for the mouse MOR gene were isolated. From one genomic clone, a 2.3-kb
      EcoRI fragment, which hybridized to the 5'-end of the rat MOR-1 cDNA probe, was
      subcloned and sequenced. This fragment contains 1.3 kb of sequence upstream of
      the initiation codon, extends downstream through exon 1 and includes a portion of
      intron 1. Primer extension analysis using mouse brain poly (A)+ RNA identified a
      transcription initiation site 793 bp upstream from the translation start site.
      Chimeric constructs of mouse MOR deletion fragments fused to a luciferase
      reporter gene were transfected into a human neuroblastoma cell line, SK-N-SH,
      which constitutively expresses endogenous MOR. These transient expression studies
      indicated that the 0.2-kb region upstream from the transcription initiation site
      possesses a functional promoter, which directs the expression of the reporter
      gene in vitro and may possess promoter activity for the mouse MOR gene in vivo.

PMID- 7648269
TI  - Activation and desensitization of Fos immunoreactivity in the rat brain following
      ethanol administration.
AB  - The expression of the Fos proto-oncogene protein has been used as an anatomical
      marker of activated brain areas. Detection of Fos immunoreactivity can provide
      information about the sites of action of various stimuli at the level of single
      cell resolution. Following intraperitoneal injection of ethanol (16% w/v), Fos
      immunoreactivity was induced in several rat brain areas including the bed nucleus
      of the stria terminalis, paraventricular hypothalamic nucleus, the central
      nucleus of amygdala, Edinger-Westphal nucleus, locus coeruleus nucleus and
      parabrachial nucleus. The induction was dose dependent, and the length of
      activation time was different in each nucleus. Fos immunoreactivity in the
      supraoptic nucleus appeared only when a higher concentration of ethanol was
      injected. Repeated administration of ethanol twice daily for 17 or 24 days
      resulted in a desensitization of Fos immunoreactivity in these nuclei. These data
      suggest that induction of Fos immunoreactivity can be used to determine the sites
      at which ethanol acts on the brain, and may provide important information about
      the mechanisms underlying the tolerance and physical dependence of alcohol usage.

PMID- 7648271
TI  - LTC law. HIV+ nurses: is there a duty to disclose their health status?

PMID- 7648270
TI  - A single intraseptal injection of nerve growth factor facilitates radial maze
      performance following damage to the medial septum in rats.
AB  - Rats were trained on a radial maze and then given electrolytic lesions of the MS
      followed by a single intraseptal injection of 5 micrograms of NGF. Three days
      later they were re-tested on the maze. They were also post-operatively tested for
      hyperemotionality. MS lesions severely impaired performance on the radial maze
      and produced increased emotionality. MS lesions also produced a general decrease
      in hippocampal high affinity choline transport and acetylcholinesterase staining,
      which was not affected by NGF administration. NGF treatment ameliorated the
      behavioral deficit in the radial maze but had no effect on the hyperemotionality.
      In order to determine whether the NGF was working to restore previously learned
      spatial abilities, the type of learning strategy used by the animals was also
      assessed. NGF treatment did not restore previously learned spatial strategies but
      facilitated recovery of alternative learning strategies. The reduction in
      cognitive deficit was also paralleled by reduced ventricular enlargement in the
      NGF treated rats. The present results suggest that a single injection of NGF can
      produce a long-lasting improvement on a cognitive task and reduce some of the
      injury-induced, secondary reactive changes that occur following electrolytic MS
      lesions.

PMID- 7648272
TI  - "OBRA" and the nursing home surveys: can they protect residents by promoting good
      nursing care?

PMID- 7648273
TI  - What nursing diagnoses do nurses use in long term care?
AB  - The results of this survey validate that the NANDA nursing diagnoses
      classification is appropriate for use in long term care. Although ninety three
      percent of the current NANDA nursing diagnoses are used in practice, there
      remains a need for the development and testing of additional nursing diagnoses to
      describe patient problems encountered in long term care. Nurses in education and
      practice settings must work collaboratively to continue to identify, refine and
      validate the nursing diagnoses that are most appropriate for frail, older and/or
      chronically ill residents of long term care facilities.

PMID- 7648274
TI  - Director's dialogue. Robin Kaufman-Storey RN BSN CDON.

PMID- 7648276
TI  - Quality begins with the family.

PMID- 7648275
TI  - National Association Directors of Nursing Administration Long Term Care
      (NADONA/LTC) position statement on AMA registered care technologist (RCT)
      proposal.

PMID- 7648277
TI  - Nursing home discharge planning ... a low profile service of growing importance.

PMID- 7648278
TI  - Incorporation of Vpr into human immunodeficiency virus type 1: role of conserved
      regions within the P6 domain of Pr55gag.
AB  - The 96-amino acid Vpr protein is the only virion-associated regulatory protein
      encoded by the human immunodeficiency virus type 1 (HIV-1). Vpr incorporation
      into the viral particle is most likely due to an interaction with a viral
      structural protein. Recent data have shown that DNA encoding for the p55 Gag
      precursor protein (Pr55gag) is the minimal viral genetic information necessary
      for Vpr incorporation. Other studies have suggested that the p6 portion of
      Pr55gag, which is unique to lentiviruses, is involved in Vpr incorporation. To
      investigate the mechanism of incorporation of Vpr into HIV-1 virions, COS-7 cells
      were cotransfected with ptrENV, an expression vector that encodes all of the HIV
      1 regulatory proteins including Rev and Vpr, and different constructs of
      pIIIgagCAR, a rev-dependent Gag expression plasmid that encodes Pr55gag and the
      viral protease. Virions produced from gag constructs containing a premature p6
      termination codon at positions Leu-1, Ser-17, Tyr-36, or Leu-44 lacked detectable
      Vpr. In contrast, gag constructs with double Pro-10-Pro-11 substitutions for Leu
      10-Leu-11 or a premature termination codon at position Pro-49 of p6 were still
      able to incorporate Vpr, however, with lower efficiency than wild type. The
      mutations described in this study affected directly two short regions within the
      p6 domain, which are highly conserved among primate immunodeficiency viruses. Our
      results suggest that the conserved (P-T/S-A-P-P) and (L-X-S-L-F-G) motifs located
      near the N-terminus and C-terminus, respectively, of the p6 domain of Gag are
      critical for Vpr incorporation into HIV-1 virions.

PMID- 7648279
TI  - Sale and exchange of syringes.

PMID- 7648280
TI  - In eastern Connecticut, IDUs purchase syringes from pharmacies but don't carry
      syringes.

PMID- 7648281
TI  - A vaccinia-gp160-based vaccine but not a gp160 protein vaccine elicits anti-gp160
      cytotoxic T lymphocytes in some HIV-1 seronegative vaccinees.
AB  - Cytotoxic T lymphocytes (CTL) play an important role in the immune response to
      viral infection by recognizing and destroying infected cells. HIV-1 elicits an
      unusually strong CTL response in infected individuals and clearance of the
      viremia of acute infection coincides with the development of HIV-specific CTL.
      Because HIV-specific CTL may provide protection against de novo viral infection,
      we compared the CTL response in seronegative volunteers treated with two
      vaccination approaches. Seven volunteers were immunized with a live recombinant
      vaccinia virus expressing the HIV envelope protein gp160LAI (HIVAC-1e) and
      boosted with 640 micrograms recombinant baculovirus-expressed gp160LAI in alum 1
      13 months later. In a second study, three volunteers underwent four successive
      immunizations with 640 micrograms subunit gp160LAI in alum at 0, 1, 6, and 12
      months. The first vaccination strategy using a liver vector would be expected to
      generate gp160-specific CTL, while for the second, using only whole-protein
      subunit, the generation of specific CTL would be unlikely. Predominantly CD8+ T
      cell lines generated from PBMC by nonspecific stimulation with PHA and IL-2 were
      screened after three to four weeks of culture for cytolytic activity against
      autologous targets infected with vaccinia vectors encoding envLAI, RT, gag, and
      lacZ control. A strong gp 160-specific CTL response was detected in two vaccines
      in the recombinant vaccinia plus subunit boost study. Modest responses were seen
      in four of the other five live vector-primed vaccinees. No significant gp160
      specific CTL were observed in three volunteers given only subunit rgp160 or in
      five control subjects.

PMID- 7648282
TI  - Anti-HIV activity of the combination of didanosine and hydroxyurea in HIV-1
      infected individuals.
AB  - HIV is known to be present in massive amounts in both resting and actively
      replicating cells in infected individuals. We tested the combination of
      didanosine and hydroxyurea, known to suppress viral production in vitro in both
      of these cell types, in a small number of asymptomatic patients. After 3 months
      of well tolerated treatment, we observed a large reduction of viral load in the
      peripheral blood of all 12 patients, down to nonquantifiable levels in 7 of 12 as
      measured by infectious virus titer, and 6 of 12 as measured by plasma HIV-RNA. In
      this subgroup of 6 patients, whose baseline HIV-RNA was below 14,000 copies/ml,
      the median increase in CD4+ count after 90 days of treatment was 244 cells/mm3.

PMID- 7648283
TI  - Diagnosis of HIV-1 infection with whole saliva by detection of antibody IgG to
      HIV-1 with ultrasensitive enzyme immunoassay using recombinant reverse
      transcriptase as antigen.
AB  - Whole-saliva samples were collected from 45 asymptomatic carriers, 18 patients
      with AIDS-related complex (ARC) or AIDS, and 76 medical students by simple
      spitting with no stimulation and tested by an ultrasensitive enzyme immunoassay
      (immune complex transfer enzyme immunoassay) for anti-HIV-1 IgG using recombinant
      reverse transcriptase as antigen and beta-D-galactosidase as label. With as
      little as 1 microliter of whole saliva, the lowest signals among the 45
      asymptomatic carriers, 8 patients with ARC, and 10 patients with AIDS were 38-,
      78-, and 3-fold, respectively, higher than the highest signal among the medical
      students. When the volume of whole saliva for test was increased up to 100
      microliters, no significant effect was observed on signals for seropositive cases
      and signals for the medical students increased only very slightly. Therefore,
      whole-saliva samples containing extremely low levels of anti-HIV-1 IgG, even
      2,000-fold lower than the lowest level among the 45 asymptomatic carriers tested,
      were considered to be discriminated from those of seronegative individuals. Thus,
      the sensitivity and specificity were expected to be both 100% with whole saliva
      even for a larger number of samples, although the number of samples tested was
      limited.

PMID- 7648284
TI  - Treatment with letrazuril of refractory cryptosporidial diarrhea complicating
      AIDS.
AB  - Thirty-five AIDS patients (mean CD4 count 44 x 10(6)/L) with chronic
      cryptosporidiosis were treated with letrazuril at an initial oral daily dose of
      50 mg in an open-label Phase I prospective trial. Treatment was continued for >
      or = 10 days and for as long as there was a response. The majority of subjects
      (91%), had previously failed paromomycin treatment. At baseline, 74% of patients
      had moderate (five to nine bowel movements per day) to severe (> 10 bowel
      movements per day) diarrhea. Twenty-three subjects (66%) had a clinical response
      within a mean of 1.7 weeks of treatment initiation. Twenty-two patients had a
      partial response (> 50% reduction in bowel movements per day for > or = 1 week),
      one patient had a complete response (two or fewer bowel movements per day). Of
      the responders, 15 (65%) had a clinical relapse with worsening diarrhea at an
      average of 1.2 months following initiation of letrazuril. The other eight (35%)
      had had symptom control for an average of 2.9 months from initiation of
      letrazuril to the latest follow-up. Microbiologic eradication was demonstrated in
      10 (40%) of 25 patients with follow-up stool examinations. Seven patients (20%)
      experienced a rash, all within 1 week of starting the drug, and resolved in all
      patients when the drug was discontinued. In conclusion, severely
      immunocompromised AIDS patients with refractory cryptosporidiosis may show a
      modest, short-lived response to letrazuril. Microbiologic response is variable
      and relapse high. Rash is a major limiting side effect of the drug.

PMID- 7648285
TI  - Pharmacokinetics of simultaneously administered zidovudine and didanosine in HIV
      seropositive male patients.
AB  - Our objective was to determine whether a pharmacokinetic interaction exists
      between zidovudine and didanosine when they are coadministered. This was designed
      as a randomized, three-period, three-treatment, six-sequence, crossover study
      with a 1-week washout period between treatments. The patients were six men
      infected with human immunodeficiency virus who were asymptomatic. On three
      separate occasions, patients received zidovudine alone (200 mg every 8 h) for 3
      days, didanosine alone (200 mg every 12 h) for 3 days, or zidovudine and
      didanosine for 3 days. On the fourth day, each patient received the final dose of
      each regimen, and blood and urine were serially collected for 8 h.
      Pharmacokinetic parameters were assessed for zidovudine, its glucuronide
      metabolite (GZDV), and didanosine. Coadministration of zidovudine had no
      significant effect on didanosine pharmacokinetic parameters (< 12% difference
      between treatment means, p > 0.1). Coadministration of didanosine did not
      significantly alter zidovudine pharmacokinetic parameters but did cause
      statistically significant increases in the renal and apparent formation
      clearances of GZDV (18.5% and 30.5% difference between the treatment means,
      respectively, p < 0.025). Therapeutic doses of zidovudine did not alter
      didanosine pharmacokinetic parameters. Coadministration of didanosine did not
      affect zidovudine parameters but did cause small alterations in GZDV
      pharmacokinetic values. These changes are unlikely to be clinically significant.

PMID- 7648286
TI  - Photodynamic therapy in AIDS-related cutaneous Kaposi's sarcoma.
AB  - For evaluating the role of photodynamic therapy (PDT) in the local treatment of
      acquired immune deficiency syndrome (AIDS)-related cutaneous Kaposi's sarcoma
      (KS), nine treatments were performed in eight human immunodeficiency virus
      positive homosexual men. The patients received 2 mg Photofrin/kg and either 120
      J/cm2 (n = 5) or 70 J/cm2 (n = 4) laser light (630 nm). A total of 83 lesions
      were evaluable for response with a follow-up of 3-8 months. The overall response
      rates by patient for all treated lesions were 50-100% (120 J/cm2) and 83.3-90.3%
      (70 J/cm2), with a median duration of 3 months (range, 2-6 months). Tumors
      located at the head had higher response rates than those at the trunk or
      extremities (p = 0.005 and p - 0.015 respectively). The size of the KS showed a
      negative relationship with the probability of complete response (p = 0.047).
      Local and general side effects occurred, including pain, blisters, temperature
      increase, muscle stiffness, and severe edema. The cosmetic result was
      unsatisfactory because of a high prevalence of scars and long-lasting
      hyperpigmentation. Although the response rates of PDT are high, light dose of 70
      120 J/cm2 cannot be recommended in the treatment of cutaneous KS in combination
      with 2 mg/kg Photofrin because of severe side effects and unsatisfactory cosmetic
      result.

PMID- 7648287
TI  - Deregulation of the sale and possession of syringes for HIV prevention among
      injection drug users.

PMID- 7648288
TI  - Impact of increased legal access to needles and syringes on community pharmacies'
      needle and syringe sales--Connecticut, 1992-1993.
AB  - In May 1992, the Connecticut legislature passed new laws aimed at increasing
      injecting drug users' (IDUs) access to sterile needles and syringes (syringes);
      as of July 1992, pharmacists were permitted to sell and individuals were
      permitted to possess up to 10 syringes without medical prescriptions
      (nonprescription syringes). We evaluated the impact of the new laws by conducting
      (1) prospective surveillance of syringe sales and policies at selected community
      pharmacies (pharmacies) and (2) a telephone survey of pharmacy managers' reports
      of syringe sales and policies at a statewide stratified random sample of
      pharmacies. Our data provide direct evidence that most, but not all, Connecticut
      pharmacies sold nonprescription syringes when permitted to do so by the new laws.
      For example, using the telephone survey data, we estimate that during November,
      1993, 83% [95% CI: 77-89%] of all Connecticut pharmacies sold nonprescription
      syringes and 56,000 [95% CI: 44,000-68,000] nonprescription syringes were sold,
      during November 1993. Our data provide indirect evidence that IDUs were
      purchasing nonprescription syringes at pharmacies. For example, in five Hartford
      pharmacies located in neighborhoods where injection drug use was prevalent, the
      total number of nonprescription syringes sold per month increased significantly
      from 460 in July 1992 to 2,482 in June 1993 (p = 0.0001). The data suggest that
      the new laws increased IDUs' access to sterile syringes in Connecticut.

PMID- 7648289
TI  - Effect of polyanionic compounds on intracutaneous and intravaginal herpesvirus
      infection in mice: impact on the search for vaginal microbicides with anti-HIV
      activity.
AB  - Several polyanionic compounds were found to suppress intracutaneous infection of
      hairless mice with herpes simplex virus type 2 (HSV-2) only when present at the
      time of inoculation. Because (a) sexual intercourse is a major route of infection
      with human immunodeficiency virus (HIV); (b) due to the species-specificity of
      HIV, there is no small animal model to study intra-vaginal HIV infection; (c) HIV
      is equally or even more sensitive than HSV-2 to several polyanions; and (d)
      sulfated polymers may prevent the adhesion of (HIV-infected) lymphocytes to
      epithelial cells, we evaluated the effect of the compounds on intravaginal
      infection of mice with HSV-2. To this end, mice were infected intravaginally with
      a virus-compound mixture. Under the conditions used, the polysulfate dextran
      sulfate conferred only partial protection against infection and virus-induced
      mortality. However, PAVAS (a co-polymer of acrylic acid with vinylalcohol
      sulfate) completely protected against the infection. These results should be
      taken into account when planning clinical studies with a vaginal polysulfate
      formulation for the prevention of sexually transmitted HIV and/or HSV-2
      infections.

PMID- 7648290
TI  - Impact of increased legal access to needles and syringes on practices of
      injecting-drug users and police officers--Connecticut, 1992-1993.
AB  - To determine whether the simultaneous, partial repeal of needle prescription and
      drug paraphernalia laws in Connecticut affected purchasing and usage of needles
      and syringes (syringes) by injecting-drug users (IDUs) and risk of needlestick
      injuries to police officers, we conducted two serial cross-sectional surveys with
      IDUs recruited in drug treatment centers, correctional facilities, and health
      department settings. Reports of needlestick injuries among Hartford police
      officers were reviewed before and after the new laws. Among IDUs who reported
      ever sharing a syringe, syringe-sharing decreased after the new laws (52% before
      vs. 31% after; p = 0.02). Fewer IDUs reported purchasing syringes on the street
      after the new laws (74% before vs. 28% after; p < 0.0001). More IDUs reported
      purchasing syringes from a pharmacy after the new laws (19% before vs. 78% after;
      p < 0.0001). Eight to eleven months after the new laws were enacted, over two
      thirds (91 of 134) of active IDUs interviewed were aware of both new laws.
      Needlestick injury rates among Hartford police officers were lower after the new
      laws (six injuries in 1,007 drug-related arrests for 6-month period before new
      laws vs. two in 1,032 arrests for 6-month period after new laws). The changes in
      Connecticut laws were associated with decreases in self-reported syringe-sharing
      and increases in purchasing by IDUs of sterile syringes from reliable sources,
      suggesting that the simultaneous repeal of both prescription and paraphernalia
      laws is an important HIV prevention strategy.

PMID- 7648291
TI  - HIV infection and AIDS risk behaviors among injecting drug users entering
      methadone treatment: an update.
AB  - Trends in HIV infection and AIDS risk behaviors among injecting drug users (IDUs)
      were assessed through a series of nonblinded point-prevalence surveys conducted
      between 1987 and 1991 with admissions to methadone treatment in eight areas,
      including New York City; Asbury Park and Trenton, New Jersey; Philadelphia;
      Baltimore; Chicago; San Antonio, Texas; and Los Angeles County. Over the 5-year
      period, significant changes in HIV seropositivity were found in two of the eight
      cities, with seroprevalence decreasing in Asbury Park from 43.1 to 21.2% and
      increasing from 10.1 to 17.6% in Chicago. Initially high levels of injection
      related risk behaviors decreased substantially across cohorts in most cities,
      except for San Antonio and Los Angeles, where risk levels remained high. Sexual
      risk behaviors continued at high levels in all cities, suggesting relatively
      little sexual risk reduction during the course of the study.

PMID- 7648292
TI  - Acquisition and use of needles and syringes by injecting drug users in Baltimore,
      Maryland.
AB  - Our objective was to determine how injection drug users (IDUs) in Baltimore,
      Maryland obtain and use needles and syringes (NS) for drug injection, before the
      opening of a needle exchange program (NEP). The method of this study was a cross
      sectional structured interview survey in 1992 of active IDUs in a longitudinal
      study of human immunodeficiency virus (HIV) infection. For 466 IDUs (94.6% black,
      83% male), usual sources of NS were "street" dealers (49.6%), pharmacies (29.8%),
      diabetics (16.3%), friends/neighbors (2.2%), and "shooting galleries" (1.9%).
      Half (53.5%) reported pharmacy purchase of NS, and 55.6% had diabetic
      friends/relatives. Twenty-three percent traded drugs, and 5% traded sex for NS.
      Eighty-eight and two-tenths percent would use a needle exchange program; 24.6%
      currently own no NS (median owned = 2.2). NS reuse was common (median = three
      times). Concern about (55.2%) or history of (33.9%) hassle/arrest for NS
      possession was typical; 81% kept NS at home, and 67% do not carry NS when
      purchasing drugs. Pharmacy purchasers (versus "street") were less likely to have
      been jailed, shared NS, or used shooting galleries during the preceding 6 months.
      In Maryland, although IDUs can legally purchase NS at pharmacist discretion,
      possession remains illegal; fewer than one-third of IDUs use pharmacies, and most
      obtain NS from illegal sources. Most IDUs reuse NS, but discard them after
      several uses. Current patterns of NS acquisition and use in Baltimore are likely
      to increase HIV transmission. Increased availability and decriminalization of NS
      possession could decrease the risk of injection-related HIV transmission.

PMID- 7648293
TI  - [Eulogy of Henri Bour (1910-1994)].

PMID- 7648294
TI  - [Epidemiology of "stress" and the problems it poses in the medical and social
      fields. The special case of acute psychic reactions to psychologic trauma].
AB  - It is important to distinguish clearly between the terms "stress" and the
      "breakdown in adaptation" which can result therefrom. Stress may be defined as
      the alert response of the organism to physical and psychological aggression. We
      need to expand our knowledge about the physiological and pathological reactions
      which occur at the onset of stress and study the importance of disturbances thus
      engendered. The direct and indirect consequences of stress and breakdown in
      adaptation also require evaluation not only from the general and occupational
      medicine viewpoint, but also sociologically. At the same time, research should be
      carried out on ways of avoiding--or at least limiting--the damaging consequences
      of exposure to stress-inducing situations, and on establishing effective
      preventive or corrective treatment. Special attention should be given to acute
      psychotraumatism.

PMID- 7648296
TI  - [HIV infection in a military environment: epidemiology, prevention, immunizations
      and fitness for service].

PMID- 7648295
TI  - [Adenovirus, a gene therapy vector: application to lung diseases].
AB  - Due to their quiescent nature and spatial complexity, many target tissues for
      gene therapy will require novel strategies. An alternative to ex vivo gene
      transfer, providing many technical advantages and possibly allowing sufficient
      transfer of the therapeutic gene, is direct in vivo delivery of the vehicle. For
      a favorable outcome, this procedure is dependent on a high-titer vector, fully
      competent before post-mitotic cells. In view of the restrictions inherent in the
      use of retroviruses, we have investigated the potentials of adenovirus.
      Adenoviruses have as primary targets of infection the differentiated epithelial
      cell. The large DNA genome of the virus hints to a large cloning capacity.
      Furthermore, wildtype adenovirus and the precedent of administration to humans
      are suggestive of adenovirus-based gene therapy for diseases involving a variety
      of quiescent tissues. The use of a replication-defective adenovirus carrying a
      gene encoding a nuclearly-targeted beta-galactosidase demonstrated that
      replication-incompetent adenoviruses offer an efficient means to transfer a gene
      for extended periods of time to the liver, muscle, lung, and brain. Because of
      adenovirus' natural tropism for the lung epithelium, we have proposed that this
      virus be used as a CFTR gene delivery vector for the treatment of cystic fibrosis
      and lung cancer.

PMID- 7648297
TI  - [Orthopedic biomaterials].
AB  - It is very challenging to insure long term security and effectiveness for joint
      arthroplasties, artificial ligaments, extensive bone replacement and some other
      orthopaedic biomaterials. How can we predict the long term security and efficacy
      of such an implant? Only an interdisciplinary approach can provide a satisfactory
      answer. The surgeon must define the needs, he must find the appropriate surgical
      techniques and conduct the clinical trial. The material scientist must elaborate
      safe and secure materials with regards to their biotolerance and mechanical
      resistance. This has to be performed in close connection with the biomechanics
      lab. Biomechanic Science must predict the expected stresses. It has to design
      special simulator to quantify in vitro material toughness, wear characteristics,
      lubrication, behaviour and surface deformation. Biological and mechanical
      standardized tests have to be carried on. Then it is possible to conduct a
      clinical trial, prospectively in comparison to another already developed
      material. Clinical studies could serve to measure efficacy and radiological
      modification. After failure, it is possible to analyse retrieved specimen, to
      measure the material degradation in real environment, to perform biological
      studies on retrieved tissues i.e. : macrophagic activities, tissue response, bone
      ingrowth, inflammatory or immunological reaction. For more than twenty years we
      worked on alumina against alumina total hips. The idea was to develop a low
      debris system to enhance long term longevity of the prosthesis. The Charnley
      design has proven its effectiveness for more than fifteen years, but polyethylene
      wear is responsible for late failures. This is specially crucial for young
      patients, male sex and high activity level patients. At the beginning, biological
      studies and mechanical tests were performed, it appeared that the biological
      tolerance of alumina ceramic was excellent, the fracture toughness was adequate,
      but there were some problems related to alumina fixation in the body and also
      alumina head fixation on metallic stem. Alumina material improved with time. It
      was possible to diminish the fracture risks and to increase the safety. Parallel
      information from the first period was used to increase the material quality, the
      surgical techniques and also to define indication in the use of such material. It
      is now clear and it also has been published that alumina against alumina system
      has proved to be as safe as Charnley total hips. It has been proved to give
      better results in the young age population. Then it is now possible to operate on
      very young patients, to allow these patients to perform heavy work, sports and
      regular daily activity for their demand.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7648299
TI  - [Bone biomaterial].
AB  - The use of deep frozen allografts is not a recent technic. The evolution of the
      conservative technics authorize a sufficient preservation of osseous and
      cartilaginous structure. The clinical results are considered as good in most of
      the cases. The intra medullary cells are most involved in immunological responses
      but clinically speaking only 10% to 20% of the case treated has a reject. The
      becoming of the grafted tissue is best if the recipient is young, the graft well
      fixed and the muscular surrounding well vascularized. 454 grafts and 64 massive
      osteochondral allografts have been archived between 1979 and 1993 for traumatic,
      tumoral, and surgical diseases. The results have been considered as good or
      excellent in 85% of the cases. The actual problems are the biomechanical
      behaviour of the ligamentary revascularization and fixation which gives in
      numerous cases a high percentage of loosening.

PMID- 7648298
TI  - [Incidents and side effects of metallic orthopedic and odontologic prostheses].
AB  - Sensitization and immune disorders from metallic prostheses are very unusual
      although most of them were metal-metal structures (nickel, cobalt or chromium
      alloys) during decades. Recent technical modifications; the use of new metal
      (titan-vanadium), of aluminum or ceramic prostheses eliminate these side effects;
      The clinical diseases may be regional (eczema, dermatitis, vascularitis) or
      general (diffuse dermatitis, itching). Some very rare systemic diseases have been
      described but their relation with the prosthesis is often uncertain. The positive
      patch tests are good indicators of the sensitization but their high prevalence of
      metal sensitization in the normal population excludes a safe diagnosis. The best
      demonstration remains the complete recovery of the disease after removal of the
      prosthesis.

PMID- 7648300
TI  - [Cardiovascular biomaterials].
AB  - Hemocompatible biomaterials, i.e. materials to be used in a biological
      environment, are of various origins (biological, synthetic). The great variety of
      physical and chemical characteristics has allowed design of various prosthesis
      and artificial organs. Use of biomaterials and artificial organs has made
      possible the development of substitutive therapies, a growing component of
      medical care. None of the biomaterials presently used is ideal. Everyone of them
      is responsible for a local and general reaction: foreign body reaction,
      coagulation, whole body inflammatory response. For years, these reactions have
      been poorly understood and development was of a very empirical nature. Progress
      in cellular and molecular biology permits today a better understanding of the
      mechanisms involved in these reactions. Use of biomaterials is facing to day a
      difficult problem; liability concerns threaten further developments and leads to
      market withdrawal of major basic materials.

PMID- 7648302
TI  - [New biomaterials and cataract surgery].
AB  - In 1949, Harold Ridley implanted the first intraocular lens, after cataract
      surgery, he had chosen as the best available material Polymethyl Metacrylate
      noticing during the war in the injured eyes of the R.A.F. Pilots that the
      material was perfectly tolerated inside the eye as a foreign body. It took 10
      years for intraocular lenses to take off, due to the necessary improvement of
      both surgery and manufacturing, since then all the intraocular lenses are made of
      the same material and perfectly tolerated. However the material is hard and not
      foldable. The improvement of Phakoemulsification have made small incision (3.2
      mm) surgery possible, however there is a need for new foldable implants that can
      be inserted into the eye through a small incision, so rather new bio material are
      now being used. A variety of silicone foldable lenses have been proposed, their
      advantages are: easy foldability, solidity and injectability through an injector.
      Their disadvantages are, as compared to the 40 years standing solid PMMA lenses;
      less biocompatibility changes in color and apparition of crystal precipitates.
      Also reports on induced polyarthritis, lupus and paraneoplasic syndromes with
      other silicone prosthesis, these complications appear after 5 or 6 years.
      Although new silicone lenses are being brought on the market, there is some
      hesitation in implanting these lenses on patients less than 80 years of age.
      Polyhema lenses appeared in 1985, with 38% water content. The material is
      perfectly biocompatible even more than PMMA, however their initial design was not
      adequate until 1992. Their advantages are perfect biocompatibility over the
      years, autoclavability. Their only disadvantage a certain fragility during
      folding. Our 7 years experience with silicone and hydrogel has shown that 20% of
      the first silicone lenses had to be exchanged between 3 to 4 years after surgery
      and 0% of the polyhema. Posterior capsule opacification at 1 year was twice more
      frequent with silicone than with PMMA or hydrogels and that mild chronic uveitis
      occurs 3 times frequently with silicone lenses.

PMID- 7648301
TI  - [Biocompatibility of cochlear implants].
AB  - Ceramic, titanium and platinum guarantee a perfect bio-compatibility for cochlear
      implants. Moreover the long term efficacy of the electrode nerve interface is
      obtained thanks to a limited electric current density. Failure risks of implanted
      electronic are decreased by use of carefully selected components.

PMID- 7648303
TI  - [Use of biomaterials in dental implantology].

PMID- 7648304
TI  - [Internal breast prostheses of silicone: accidents and medico-legal
      consequences].
AB  - The authors gathered the principal information obtained from medical and
      medicolegal data relating to silicone breast implants. The publications collected
      and the opinions of various administrative, judiciary and private authorities do
      not permit at present to determine a complete coherent point of view. The
      internal silicone breast implants could provoke some inflammatory phenomenons and
      local sclerosis. The durability and life span of these prostheses is still matter
      of concern. Though not proved by epidemiological studies the risk of group
      connective-tissue diseases cannot be definitely dismissed 10 years after the
      prosthesis implantation, the risk is probably low. Finally the practitioners,
      especially cancerologists, should continue to use these prostheses. It is to hope
      that experimental epidemiological research and the progress of manufacturing
      control allow the use of silicones for medical and chirurgical purposes.

PMID- 7648306
TI  - [Meeting devoted to the presentation of the report on genetic diagnosis and gene
      therapy].

PMID- 7648305
TI  - [Artificial urinary sphincter].
AB  - The artificial urinary sphincter is a totally implantable hydraulic prosthesis
      designed to restore continence without inducing dysuria. It is composed of 3
      silicone elastomer elements: a periurethral or pericervical cuff, a pressure
      regulating reservoir balloon inserted in the retropubic space, and a pump
      situated in the scrotum or labia majora. The prosthesis is filled with a liquid
      containing a contrast agent. Pressure on the pump allows passage of liquid from
      the cuff towards the balloon and allows micturition. After 3 to 4 minutes, the
      liquid is automatically transferred from the balloon to the cuff to restore
      continence. The artificial sphincter is currently a very effective therapeutic
      solution in cases of severe urinary incontinence with 3 main indications:
      persistent incontinence after prostatic surgery, recurrent incontinence in women
      due to sphincter insufficiency, and certain forms of neurogenic incontinence. The
      Pitie-Salpetriere Urology Department's experience currently consists of 200
      implantations performed over the last 10 years. The overall success rate varies
      from 80 to 90% according to sex and the aetiology of incontinence, in patients in
      whom the sphincter remains in place. In fact, there is a risk of explantation due
      to erosion of the tissues by the cuff or infection, but this risk is less than
      15%. The risk of prosthesis failure is about 20%, but after correction of the
      defective element, cure is achieved in almost every case. Analysis of the results
      in the first 120 patients with the two most frequent aetiologies and with at
      least three years' follow-up (range: 3 to 10 years) reveals: in a series of 75
      men, treated for severe incontinence persisting more than one year after surgery
      for benign prostatic hyperplasia, the explantation rate was 15% and, in the
      patients in whom the sphincter remained in place, complete cure was obtained in
      73% of cases without any incontinence, while 17% of patients suffered from
      minimal incontinence, not requiring protection, 7% had moderate incontinence
      requiring protection and 3% were considered to be failures. The revision rate for
      technical failure was 24%. In a series of 45 women with recurrent incontinence
      after surgery, due to sphincter insufficiency, the explanation rate was 13% and,
      in women in whom the sphincter remained in place, complete success was obtain in
      78% of cases without any incontinence, while 17% suffered from minimal
      incontinence, usually not requiring protection, 5% require protection, with no
      failures and a revision rate for technical failure of 24%.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 7648307
TI  - [Comparative analysis of the immune response in a case of primary regressive
      melanoma followed by gastric metastasis].
AB  - The theory of immunosurveillance against cancer has been an extensively debated
      question over the last decades. Multiple indirect arguments have supported the
      view that the immune system may control, at least in certain cases, malignant
      cell growth while direct demonstration is still lacking in the human. In an
      attempt to address this issue, we have selected a study model, namely
      spontaneously regressive melanoma. A primary cutaneous lesion was investigated. T
      cell repertoire analysis showed the in situ amplification of at least two tumor
      infiltrating lymphocyte (TILs) expressing the V beta 13 and V beta 16 variable
      TCR gene segments respectively. The two clones were precisely characterized by
      sequence of the TCR beta chain junctional region. Further functional study
      demonstrated that both lymphocytes displayed a selective cytotoxic activity
      against autologous tumor cells. The V beta 16+ cells, predominant in vivo, were
      shown to be closely opposed to the melanoma cells. Together, these studies
      demonstrated the existence of a local adaptative immune response associated to
      tumor regression, thus strongly supporting the validity of the immunosurveillance
      concept. A gastric metastasis which occurred three years after the primary lesion
      has been studied here. Overexpression of the V beta 13 and V beta 16 TCR segments
      was no longer detected by direct PCR analysis in situ. Sequencing transcripts
      from V beta 13+ and V beta 16+ TILs confirmed that the two CTLs, identified in
      the primary lesions, were not represented with high frequency. The V beta 13+
      cell was however shown to be present while the V beta 16+ CTL was not detected.
      Yet, characterization of a tumor cell line derived from the gastric site
      indicated that the peptidic antigen(s) which induced the initially successfully
      immune response was still expressed. The present data illustrate that it has
      become possible to perform very precise analysis of local immune responses during
      cancer development. Such an improvement together with the recently initiated
      molecular characterization of tumor associated peptidic antigens, should provide
      the basis for improved strategies of cancer immunotherapy.

PMID- 7648308
TI  - [Breast cancer: role of MRI in follow-up of cases treated].
AB  - Conventional imaging (CI) for breast cancer includes mammography and ultrasound.
      Its limited efficiency is especially manifest for breast cancer follow-up after
      breast-conserving therapy (i.e. exclusive radiation therapy) and after breast
      implant. Lack of evidence for definitive diagnosis increases the number of
      invasive explorations. To improve the specificity of the diagnosis between
      recurrence or fibrosis, we describe the interest of new imaging (NI) techniques:
      post-contrast MRI, and MR angiography (MRA), realized in 1 exam. Between October
      1993 and December 1994, 82 patients were eligible for these investigations. All
      patients had an history of conservative breast cancer treatment of breast implant
      following mastectomy. In all cases CI was not contributive for a precise
      diagnosis; therefore a biopsy was performed and confirmed the diagnosis of breast
      cancer. NI was done before biopsy and compared results are following. 19 more
      patients were evaluated for primary chemotherapeutic response, including a total
      of 101 patients. Regarding the follow-up of prosthesis and conservative
      treatment, the correlation with histological control was obtained in 95% with
      four false diagnoses due to confusion between retroprosthesis relapse and
      inflammation. Historadiologic correlation were close to 90% for the evaluation of
      primary chemotherapeutic response. Studies are ongoing to confirm those
      preliminary findings. Though expansive, these techniques might be cost-effective
      if they result in a substantial decrease of unnecessary surgical invasive
      procedures.

PMID- 7648309
TI  - [Eulogy of Pierre Goret (1907-1994)].

PMID- 7648310
TI  - [Heredity and manic-depressive psychosis].
AB  - The present article reviews the basic and recent findings of the genetics in
      manic-depressive illness. The different molecular genetic techniques that have
      been applied to this research field are presented. Results of linkage and
      association studies are discussed in regard to the main limitations of these
      approaches in psychiatric disorders. On the whole, linkage and association
      studies contributed to the localisation of some potentials vulnerability genes
      for manic-depression on chromosomes X and 11 and more recently 18.

PMID- 7648311
TI  - [Contribution of the experimental model of bacterial endocarditis].
AB  - Bacterial endocarditis is a difficult to cure infection, due to poor penetration
      of antibiotics into infected vegetations, altered metabolic state of bacteria
      within the lesion, and absence of adequate host-defense cellular response which
      could cooperate with antibiotic action. The contribution of animal models to a
      better understanding of the pathophysiology of the infection and to definition
      and improvement of therapeutic regimens of endocarditis in humans, remains of
      great importance due to the difficulties encountered in clinical trials. The
      advantage of the experimental model is that besides the fact that is closely
      simulates the characteristics of the infection in humans, it provides clear
      endpoints which allow statistical comparisons among different therapeutic
      regimens. The animal model has definitively established that bactericidal therapy
      is warranted and that in vitro susceptibility tests, especially those evaluating
      the killing rate, have a good predictive value on therapeutic outcome. Two main
      aspects are discussed for their relevance to human therapy and represent our
      recent contribution: (i) the kinetics of antibiotic diffusion into vegetations,
      with special reference to data obtained with autoradiography; and (ii) the
      specificity of some pharmacodynamic aspects of antibiotics in endocarditis. This
      animal model has also helped to define the importance of antibiotic dosing
      strategies to achieve in vivo synergism and to outline the predictive value of
      some drug pharmacokinetic and dynamic properties on the in vivo response to
      therapy.

PMID- 7648313
TI  - [Promotion of health examinations oriented toward surveillance of aptitude for
      physical effort].

PMID- 7648312
TI  - [Invasive cysticercosis due to Taenia crassiceps in an AIDS patient].
AB  - A first case is reported from France of a subcutaneous and muscular tissues
      invasion by proliferative larval forms of Taenia crassiceps in an AIDS-patient
      with severe immunodeficiency. These larvae usually develop in rodents whereas the
      adult form of the cestode is commonly found in foxes. Authors emphasize the
      differential diagnosis from other human subcutaneous metacestodoses such as T.
      solium cysticercosis, cenurosis and hydatidosis. The proliferative aspect of the
      larvae, the recurrence of lesions after surgical removal and the possible
      invasion of other tissues are elements of a poor prognosis.

PMID- 7648314
TI  - [A very up-to-date stage in the fate of infectious diseases: parasitic and fungal
      opportunistic infections].
AB  - Opportunistic parasitosis and mycosis are becoming ever more widespread, mainly
      under the influence of major immunodeficiencies, either acquired (AIDS) or
      therapeutic. In this general overview, their main aspects, both clinical and
      epidemiological, are underlined. In terms of epidemiology, three types of
      phenomena have been observed: 1) emergence of human parasitosis unknown before
      (microsporidiosis due to Enterocytozoon bieneusi, Encephalitozoom hellem or
      Septata intestinalis); 2) among the human parasites already known, identification
      of very pathogenic strains (Toxoplasma gondii, Aspergillus fumigatus,
      Cryptococcus neoformans); 3) origin probably or certainly nosocomial of certain
      infections (pneumocystosis; toxoplasmosis and visceral leishmaniasis transmitted
      during bone-marrow or organ transplantations). The development of deep mycosis
      (invasive aspergillosis) is particularly promoted by granulopenia and alterations
      in the phagocytosis. On the other hand, opportunistic protozoosis (toxoplasmosis
      and leishmaniasis) and helminthiasis (strongyloidosis due to Strongyloides
      stercolaris) are related, above all, to disorders in cellular immunity (deficit
      of CD4+, mainly). Finally, several of these infections may be characterised by a
      variety of clinical pictures and outcome, depending on the contributory factors
      (immunodeficit or not) which led to the development of the infection.

PMID- 7648315
TI  - [A very current aspect of the fate of infectious diseases: tuberculosis, leprosy
      and opportunistic mycobacteria].
AB  - The human mycobacterial diseases, such as tuberculosis and leprosy, are chronic
      infectious diseases and have been present for a long period of time with human
      beings. Clearly tuberculosis and leprosy have been on the wane long before
      effective therapy was introduced, each of them having a natural epidemic
      evolution, with onset, peak and decline. Such decline was apparently accelerating
      in recent decades, due to individual and collective measures aiming at
      controlling the diseases, and it gives the hope of their possible elimination in
      the early XXIe century. If for leprosy recent data seems to indicate a realistic
      hope, such one has been destroyed for tuberculosis, since worldwide reemergence
      of cases occurs, which was associated with non application of control measures
      and occurrence of the HIV infection. Such coinfection leads to immunodeficiency
      that increases the risk of tuberculosis and the development of disseminated
      opportunistic mycobacterioses, mostly due to M. avium. An increased persevering
      action in the control measures and the development of new ways of research on
      mycobacterial infections are even more necessary if one will master such
      devastating plaques.

PMID- 7648316
TI  - Virus structures and conformational rearrangements.
AB  - Structural virology is a burgeoning subspecialty. Our understanding of the
      molecular organization of viruses has begun to contribute directly to the
      analysis of viral attachment and entry, assembly, antigenicity, and even viral
      pathogenesis, but there are still more puzzles than answers. Recent
      crystallographic results have helped us to understand the structural changes in
      viruses that affect their assembly and infectivity.

PMID- 7648317
TI  - AB5 toxins.
AB  - Crystal structures of shiga and pertussis toxins have recently revealed a
      remarkable degree of structural homology among the members of the AB5 class of
      bacterial toxins. Other structures have provided a detailed view of the molecular
      basis of receptor binding specificity of cholera toxin, and of the heat-labile
      enterotoxin of Escherichia coli. These structures also provide tantalizing, but
      as yet incomplete, information on the site of ADP-ribosylation in the homologous
      A-subunits of the Escherichia coli heat-labile toxin, cholera toxin, and
      pertussis toxin.

PMID- 7648318
TI  - New insights into actin filament dynamics.
AB  - Great progress has been made in advancing an atomic-level model for F-actin. A
      growing body of data shows, however, that any picture of F-actin must take into
      account allosteric interactions within subunits, long-range cooperative effects
      that occur between subunits, and the fact that several conformations of the
      filament can exist.

PMID- 7648319
TI  - Myosin structure/function: a combined mutagenesis-crystallography approach.
AB  - In the past year, the structure of the regulatory domain of scallop myosin has
      joined that of the chicken skeletal muscle myosin subfragment 1 and provided
      insights into the regulation of myosin function. Mutagenesis studies in a variety
      of systems have used the information provided by these structures to create
      mutant myosins to test models of chemomechanical transduction and its regulation.

PMID- 7648320
TI  - Spinning tails.
AB  - The torque-generating, direction-reversing switch proteins of the bacterial
      flagellar rotary motor form a cytoplasmic extension of the bacterial flagellar
      basal body. 10 A maps, obtained by electron cryomicroscopy, of the bacterial
      filament reveal an unusual alpha domain which forms the protein-subunit export
      channel. The details of subunit export, assembly, and assembly-monitoring
      machinery are becoming clearer.

PMID- 7648321
TI  - Approaches to large-scale structures.
AB  - Quantitative three-dimensional (3D) maps of large-scale structures can now be
      routinely obtained by the use of high- or intermediate-voltage electron
      tomography. The recent 3D reconstructions of the mitochondrion and the Golgi
      apparatus highlight both the potential and the shortcomings of this technique.
      New technological developments, in particular the development of automated low
      dose electron tomography, are expected to facilitate the 3D visualization of
      large structures in the fully hydrated environment, embedded in vitreous ice.

PMID- 7648322
TI  - Potential energy functions.
AB  - When energy is a critical quantity, accurate biomolecular simulations rest in
      substantial part on accurate potential energy functions (force fields).
      Improvements in methodology for determining parameters--particularly, in the
      systematic use of computational data obtained from quantum chemical calculations-
      and enhancements in functional form are leading to better potential energy
      functions. New calculations have been developed for water (including calculations
      that incorporate electronic polarizability to take account of the degree to which
      a molecule can be polarized), proteins, nucleic acids, carbohydrates, lipids, and
      general organic molecules. Most notably, two new biomolecular force fields have
      recently been derived and significant redeterminations of the parameters of two
      existing biomolecular force fields have been carried out. Some progress has also
      been made in incorporating polarizability into potential energy functions for
      molecules in general and in improving the treatment of metal-ligand interactions
      in systems of biomolecular interest.

PMID- 7648323
TI  - Methodological advances in molecular dynamics simulations of biological systems.
AB  - New advances in the techniques used to simulate specific statistical ensembles
      provide molecular dynamics algorithms that permit rigorous connections to be made
      between thermodynamic observables and calculated quantities in simulations of
      biological molecules. The complete inclusion of electrostatic forces in
      simulations also improves the comparison between calculations of simple
      structural measures in crystals and X-ray crystallographic results. These
      advances coupled with the ongoing development of more accurate
      inter/intramolecular forcefields with enhanced accuracy provide guidelines and
      benchmarks for comparison as we move to study more complicated biological
      problems.

PMID- 7648324
TI  - Theory of electrostatic interactions in macromolecules.
AB  - In the past year, substantial progress has been made in the modeling of
      electrostatic interactions in biomolecules. This review highlights advances in
      the following areas: first, the efficient computation of long-range electrostatic
      interactions in detailed molecular simulations; second, the application of the
      Poisson-Boltzmann electrostatic model in conformational analysis; third, the
      application of the Poisson-Boltzmann model in quantum chemistry calculations;
      fourth, the development of atomic parameters; and finally, the modeling of
      ionization equilibria in proteins.

PMID- 7648325
TI  - Ligand-protein docking and rational drug design.
AB  - Over the past year there have been some interesting and significant advances in
      computer-based ligand-protein docking techniques and related rational drug-design
      tools, including flexible ligand docking and better estimation of binding free
      energies and solvation energies. As a result, the successful use of computational
      tools to help generate interesting new guide (lead) compounds for targeted
      receptors is becoming more commonplace.

PMID- 7648327
TI  - Statistics of sequence-structure threading.
AB  - The past two years have seen the rapid development of new recognition methods for
      protein structure prediction. These algorithms 'thread' the sequence of one
      protein through the known structure of another, looking for an alignment that
      corresponds to an energetically favorable model structure. Because they are based
      on energy calculation, rather than evolutionary distance, these methods extend
      the possibility of structure prediction by comparative modeling to a larger class
      of new sequences, where similarity to known structures is recognizable by no
      other means. The strength of the evidence they offer should be judged by
      objective statistical tests, however, so as to rule out the possibility that
      favorable scores arise from chance factors such as similarity of length,
      composition, or the consideration of a large number of alternative alignments.
      Calculation of objective p-values by analytical means is not yet possible, but it
      would appear that approximate values may be obtained by simulation, as they are
      in gapped, global sequence alignment. We propose that the results of threading
      experiments should include Z-scores relative to the composition-corrected score
      distribution obtained for shuffled and optimally aligned sequences.

PMID- 7648326
TI  - Knowledge-based potentials for proteins.
AB  - Knowledge based potentials and energy functions are extracted from a number of
      databases of known protein structures. Recent developments have shown that this
      type of potential is successful in many areas of protein structure research.
      Among these are quality assessment and error recognition of folds and the
      prediction of unknown structures by fold-recognition techniques.

PMID- 7648329
TI  - Macromolecular assemblages.

PMID- 7648328
TI  - Modeling superhelical DNA: recent analytical and dynamic approaches.
AB  - During the past year, a variety of diverse and complementary approaches have been
      presented for modeling superhelical DNA, offering new physical and biological
      insights into fundamental functional processes of DNA. Analytical approaches have
      probed deeper into the effects of entropy and thermal fluctuations on DNA
      structure and on various topological constraints induced by DNA-binding proteins.
      In tandem, new kinetic approaches--by molecular, Langevin and Brownian dynamics,
      as well as extensions of elastic-rod theory--have begun to offer dynamic
      information associated with supercoiling. Such dynamic approaches, along with
      other equilibrium studies, are refining the basic elastic-rod and polymer
      framework and incorporating more realistic treatments of salt and sequence
      specific features. These collective advances in modeling large DNA molecules, in
      concert with technological innovations, are pointing to an exciting interplay
      between theory and experiment on the horizon.

PMID- 7648330
TI  - Theory and simulation.

PMID- 7648331
TI  - Hepatic uptake of glutamine and other amino acids during infection and
      inflammation.
AB  - Catabolic illness such as sepsis and injury induce profound changes in host amino
      acid metabolism, including increased hepatic amino acid uptake. Because many
      amino acid-dependent pathways such as gluconeogenesis and acute-phase protein
      synthesis are activated in the liver during severe infection, this review will
      focus on the control of hepatic plasma membrane amino acid transport by specific
      inflammatory mediators. We specifically review the role of cytokines,
      eicosanoids, and glucorticoids in this response. Collectively, these signaling
      molecules act in a concerted manner to exert local control of hepatic function
      including the stimulation of amino acid transport. In particular, we review the
      role of glutamine and its transport in the liver, as it occupies a unique role in
      interorgan ammonia metabolism during critical illness.

PMID- 7648332
TI  - Bacterial translocation-related mortality may be associated with neutrophil
      mediated organ damage.
AB  - Balb/c mice were transfused with .2 mL of C3H/HeJ mouse blood. 5 days later, the
      mice were gavaged with 10(10) 14C-labeled Escherichia coli, and a 20% full
      thickness flame burn was inflicted. Additional animals were treated with
      enisoprost (prostaglandin E1 (PGE1) analog) 200 micrograms/kg/day orally for 3
      days before burn. Bacterial translocation was determined by both radionuclide
      counts (dpm) and viable colony counts 24 h post burn. Neutrophil accumulation was
      evaluated by the measurement of myeloperoxidase (MPO) in the liver. In addition,
      splenic macrophages were separated and cultured for 24 h with or without 10
      micrograms/mL of LPS. Tumor necrosis factor, interleukin-1 (IL-1), IL-6, and PGE2
      were measured in the cell culture supernatants. Consistent with previous work,
      enisoprost significantly reduced translocation. MPO in the liver was
      significantly greater in the control group compared to the enisoprost group.
      There was a significant correlation between MPO content and the degree of
      bacterial translocation (p < .05). Lipopolysaccharide-stimulated macrophage
      production of IL-1, IL-6, and PGE2 were significantly greater in the enisoprost
      group.

PMID- 7648333
TI  - Anti-lipid A monoclonal antibodies alter human endothelial cell ICAM-1 expression
      in vitro.
AB  - Two murine anti-lipid A MAbs (A78S1 and A523), which were protective in a rat
      model of neonatal endotoxin shock (Goto, M, Zeller WP, Hurley RM, Jong JS, Lee C
      H: Prophylaxis and treatment of newborn endotoxic shock with anti-lipid A
      monoclonal antibodies. Circ Shock 35:60-64, 1991), were tested for their effects
      on lipid A-induced ICAM-1 expression by cultured human umbilical vein endothelial
      cells (HUVEC). In the presence of 5% fetal bovine serum, lipid A-induced ICAM-1
      expression, as measured by radioimmunoassay following 18 h incubation, was
      enhanced by A78S1 at lower concentrations (.02-.2 micrograms/ mL) but was
      inhibited at concentrations of 20 micrograms/mL or greater. Its control
      immunoglobulin, purified nonspecific IgG2b, enhanced the lipid A-stimulated ICAM
      expression at all concentrations tested. Neither MAb A523 nor its control
      immunoglobulin, purified nonspecific IgM, had effects on the lipid A-stimulated
      ICAM-1 by HUVEC. Although A78S1 and A523 had no direct effects, the control
      immunoglobulins marginally stimulated ICAM-1 activity at their highest
      concentrations (possibly due to the presence of endotoxin). Furthermore, in serum
      free medium all of the immunoglobulins dose-dependently stimulated ICAM-1
      expression. These results demonstrate that anti-lipid A MAbs and other
      immunoglobulins can exhibit variable effects on unstimulated or lipid A
      stimulated ICAM-1 expression by HUVEC depending upon the presence of serum, their
      concentration, immunoglobulin subclass, or epitope specificity.

PMID- 7648334
TI  - Calcium antagonists decrease plasma and tissue concentrations of tumor necrosis
      factor-alpha, interleukin-1 beta, and interleukin-1 alpha in a mouse model of
      endotoxin.
AB  - Calcium plays an important role in the toxic effects of endotoxin, and calcium
      antagonists also have been shown to improve survival in animals challenged with
      endotoxin. Calcium may be involved in regulating cytokine production. Therefore,
      the protective effect of calcium-antagonists in endotoxin may be due to decreased
      cytokine formation and/or systemic release. In a mouse model of endotoxin,
      dantrolene (10 mg/kg) and azumolene (20 mg/kg), drugs that decrease calcium
      release from intracellular stores, or diltiazem (20 mg/kg), a calcium channel
      blocker, decreased plasma tumor necrosis factor-alpha (TNF-alpha), interleukin-1
      alpha (IL-1 alpha), and IL-1 beta (47.2, 63.2, and 62.4%, respectively, p < .05)
      when the animals were injected intraperitoneally with endotoxin. Dantrolene and
      azumolene decreased IL-1 alpha by 56.6 and 65.4%, respectively, (p < .05) and IL
      1 beta by 51.7 and 69.7%, respectively (p < .05). Diltiazem had no effect on IL-1
      alpha or IL-1 beta. Dantrolene decreased TNF-alpha in lung (26.1%), liver
      (29.4%), and spleen (35.4%) (p < .05) and IL-1 alpha in lung (30.0%) and liver
      (25.4%) (p < .05). The present findings indicate that calcium-antagonists may be
      efficacious in treating cytokine mediated inflammatory disorders.

PMID- 7648335
TI  - Plasma and tissue histamine changes during hemorrhagic shock in the rat.
AB  - We investigated the phase-associated changes in plasma histamine levels in an
      isobaric model of hemorrhagic shock, in an attempt to determine whether histamine
      might be an etiologic factor in the onset of decompensation. Sprague-Dawley rats
      were bled according to an isobaric bleeding protocol which maintained the mean
      arterial blood pressure at 40 mmHg until death. The status of vascular
      compensation for the blood loss was tracked by measurement of the shed blood
      volume (SBV) required to maintain the target pressure. Blood samples for analysis
      were taken at the control period and at 25% intervals of the peak shed blood
      volume (PSBV) during the compensatory and decompensatory phases. Plasma and
      tissue histamine levels were measured using a radioimmunoassay method. In
      untreated animals, plasma histamine levels at control, 75 and 100% of the PSBV,
      and after return of 25 and 75% of the PSBV were 45 +/- 10, 48 +/- 9,134 +/-
      48,693 +/- 351, and 994 +/- 371 nM, respectively. These results show that rises
      in plasma histamine occurred coincidentally with the onset of decompensation (p <
      .05), however, the subsequent rate of decompensation did not correlate with
      plasma histamine changes during decompensation. Organ histamine levels measured
      after hemorrhage were lower in the duodenum and colon than in unbled control
      animals, suggesting that parts of the intestinal tract may contribute to the
      elevated plasma histamine levels seen in severe hypotension (p < .05).

PMID- 7648336
TI  - Fluid shifts following 7% hypertonic saline (2400 mosmol/L) infusion.
AB  - Small volumes of hyperosmolar saline solutions may rapidly improve MAP and CO in
      hemorrhagic shock. In the present study, the effects of infusion of 7% NaCl on
      interstitial fluid volume and intracellular fluid volume were determined. In
      anesthetized, normovolemic rats either 7% NaCl (1.1 mL/100 g, intravenously),
      acetated Ringer's solution (10 mL/100 g), or no fluid (controls) were infused and
      extracellular volume (ECV) and plasma volume were determined in samples from
      skin, skeletal muscle, small intestine, liver, and lung. Intracellular volume was
      determined as local tissue water content minus ECV. Extracellular fluid volumes
      were 21.1 +/- .6 mL/ 100 g(mean +/- SEM; n = 6) (control animals), 26.1 +/- .4
      mL/100 g (following 7% NaCl) (p < .05), and 32.8 +/- .5 mL/100 g (following
      Ringer's) (p < .05). Following 7% NaCl ECV increased by four to five times the
      infused volume. With 7% NaCl ECV in skin, muscle and intestine increased
      significantly, whereas cell volume was reduced by 10% in muscle and liver.
      Skeletal muscle, constituting > 40% of body mass with a large cell volume, was
      the main source for fluid mobilized by administration of 7% NaCl.

PMID- 7648337
TI  - Comparison between the effects of central and systemic hypertonic NaCl on
      hemodynamic responses to hemorrhage in sheep.
AB  - Effects of treatment with systemic hypertonic (1.2M, 4 mL kg-1) NaCl (SHTNa) on
      tolerance to hemorrhage, accompanying systemic hemodynamics, and regional blood
      flow were investigated in conscious sheep. The results were compared with those
      obtained in animals subjected to hemorrhage during intracerebroventricular (ICV)
      administration of hypertonic (.5 M, .02 mL min -1) NaCl (CHTNa). Corresponding
      bleeding during ICV infusion of isotonic saline served as control. All treatments
      were started 30 min before commencement of a slow (.7 mL kg-1 min-1) hemorrhage,
      which was continued until the mean systemic arterial pressure (MSAP) suddenly
      dropped to about 50 mmHg. To reach the distinct fall in MSAP significantly more
      blood had to be withdrawn in the CHTNa (27.8 +/- 2.2 mL kg-1, p < .05) than in
      the SHTNa group (21.5 +/- 1.7 mL kg-1), which in turn showed a significantly
      higher tolerance to hemorrhage than the controls (15.1 +/- .7 mL kg-1, p < .01).
      The hemorrhage-induced reduction of cardiac output (CO) below basal level was
      less pronounced in the CHTNa group, where also the posthemorrhage CO recovery was
      most rapid. Spontaneous recovery of MSAP after bleeding was equally improved in
      both treatment groups with the central venous pressure being significantly higher
      in the SHTNa group. The hemorrhage-induced fall in renal blood flow (RBF) was
      more pronounced in the CHTNa group, which also had an impaired posthemorrhage
      recovery of RBF. In comparison to the SHTNa and control groups the renovascular
      resistance was significantly higher in the CHTNa group already during the
      prehemorrhage infusion period.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7648338
TI  - Comparison of plasma cytokine levels in rats subjected to superior mesenteric
      artery occlusion or hemorrhagic shock.
AB  - The overall goal of this study was to compare the effects of systemic hypotension
      (hemorrhagic shock) versus local gut ischemia (superior mesenteric artery (SMA)
      occlusion) on cytokine production and bacteria/endotoxin translocation. Sham or
      actual SMA occlusion led to an increase in tumor necrosis factor (TNF), which was
      greatest at the end of the occlusion period, while the IL-6 response peaked 3 h
      post-SMA occlusion. The TNF and IL-6 response after hemorrhagic shock differed
      from that observed after SMA occlusion in that the peak response occurred later
      and was of lower magnitude (p < .05). Although the animals subjected to SMA
      occlusion had a significantly increased incidence of bacterial translocation to
      both the mesenteric lymph nodes and systemic organs compared to rats subjected to
      hemorrhagic shock, in neither group was the blood level of endotoxin elevated and
      there was no association between bacterial translocation and cytokine levels.
      These results suggest that different models of intestinal ischemia have different
      cytokine profiles and that the early TNF response associated with SMA occlusion
      model is primarily due to the laparotomy.

PMID- 7648339
TI  - Maintenance of dynamic microvascular function and structure in a rat model of
      endotoxic shock by blockade of the interleukin-1 receptor.
AB  - The microvascular and macrovascular effects of IL-1 receptor antagonist (IL-1ra)
      were examined in rat cremaster muscle A1, A2, and A3 arterioles by
      videomicroscopy to better define its protective effects during endotoxemia. Mean
      arterial pressure (MAP), arteriolar diameters, and responses to norepinephrine
      (NE) and acetylcholine (ACh) were examined hourly after the administration of
      Escherichia coli endotoxin (6 mg/kg intravenously). Animals received saline
      (Control) or IL-1ra (.2 mg/kg/min intravenously) beginning 1 h prior to
      endotoxin. Serum tumor necrosis factor-alpha (TNF-alpha) and nitrate/nitrite (NO)
      were determined terminally. Aortic endothelium was examined by electron
      microscopy (EM). All Control animals, but no IL-1ra animals, died within 6 h (p <
      .01).IL-1ra significantly attenuated endotoxin-induced vasoconstriction of A1 and
      A2 arterioles (p < .01), while MAP and NE threshold remained at baseline (p < .01
      vs. Control). Serum TNF and NO were elevated following endotoxin (p < .001), but
      only TNF was decreased (p < .005) in animals receiving IL-1ra. Aortic endothelium
      was damaged in all Control animals but was spared with IL-1 antagonism. IL-1ra
      increases survival during endotoxic shock and attenuates production of TNF but
      not NO. IL-1ra maintains MAP, arteriolar diameters, reactivity of arterioles to
      NE and ACh, and the integrity of the aortic endothelium.

PMID- 7648340
TI  - Involvement of bradykinin and nitric oxide in the early hemodynamic effects of
      lipopolysaccharide in rats.
AB  - The involvement of bradykinin and nitric oxide (NO) in the early (within 1 h)
      hemodynamic effects of bacterial lipopolysaccharide (LPS) were investigated in
      anaesthetised rats. Infusion of rats with LPS (14 mg/kg/h) produced a transient
      hypotension (nadir at 20 min) and reduced pressor responses to noradrenaline
      (NA,.1-1 microgram/kg, intravenously (i.v.)). Pretreatment of rats with NG-nitro
      L-arginine methylester (L-NAME, 1 mg/kg, i.v.) produced a hypertension which
      counteracted but did not abolish the hypotension induced by LPS, although it
      entirely prevented LPS-induced hyporeactivity to NA. In control rats, the
      bradykinin B2 receptors antagonist HOE 140 (10 nmol/kg, i.v.) produced a
      transient hypotension, but it did not modify the reactivity to NA. In rats
      pretreated with HOE 140, subsequently infused with LPS, the drop in blood
      pressure and its time course after the onset of LPS infusion were not different
      from those elicited by HOE 140 or LPS separately. In addition, HOE 140 partially
      prevented the onset of hyporesponsiveness to NA induced by LPS. These results
      support the view that both bradykinin and NO are involved in the early
      hyporesponsiveness to NA. They suggest that other mechanisms than NO release are
      involved in the early hypotensive effects of LPS.

PMID- 7648341
TI  - Direct action of endotoxin on cardiac muscle.
AB  - While the cardiovascular effects of endotoxin include myocardial depression,
      presumably due to circulating myocardial depressant substances, endotoxin itself
      is supposed to have no direct effect on the heart. In these experiments, we
      compared the direct effects of endotoxin on the contractile response of feline
      papillary muscle to calcium with that seen after administration to the intact
      animal. The contractile state of the muscle was assessed from developed tension
      as extracellular calcium concentrations were varied from .5 to 8.0 mM. When
      endotoxin was administered to the intact animal as well as given to the muscle
      directly in the bathing solution, endotoxin- exposed muscles showed smaller
      increases in contractile tension with increasing calcium concentrations than
      control muscles after 70-85 min. NaOH-inactivated endotoxin produced results
      similar to the control experiments. Previous experimenters have reported
      myocardial depression only after endotoxin had circulated in the intact animal
      for 1-2h; these experiments show a direct depressant effect of endotoxin on
      cardiac muscle without the release of a substance elsewhere in the body.

PMID- 7648342
TI  - Protective effect of a 21-aminosteroid against hemorrhage-induced ischemia
      reperfusion injury in the rat stomach: role of lipid peroxidation.
AB  - We investigated the role that lipid peroxidation plays in a hemorrhage-induced
      ischemia-reperfusion model of gastric injury. Rats were pretreated with an
      inhibitor of this process, a 21-aminosteroid (U-74389G, 10 mg/kg), or an
      appropriate control solution intravenously 15 min prior to 20 min of ischemia,
      followed by 20 min of reperfusion. Results indicated that U-74389G pretreatment
      significantly attenuated gastric damage compared with corresponding control
      animals (19.8 vs. 176.8 mm2, p < .001). Enaldehyde levels (picomoles/mg protein),
      a biochemical index of lipid peroxidation, paralleled these injury findings (12
      vs 960, p < .001). Histologically, U-74389G pretreatment almost completely
      prevented gastric injury compared to control stomachs. Additional studies
      revealed that lipid peroxidation preceded the formation of gastric damage, and
      injury occurred predominantly during reperfusion, because animals subjected to
      ischemia alone without reperfusion failed to develop appreciable injury or
      enhanced enaldehyde formation. Further, if U-74389G was given intravenously after
      ischemia, but prior to reperfusion, gastric injury and enaldehyde formation were
      similarly attenuated. Our findings are consistent with the hypothesis that lipid
      peroxidation likely plays an important role in hemorrhage-induced ischemia
      reperfusion injury to the stomach.

PMID- 7648343
TI  - Antiphospholipids--a "guilty ghost" syndrome.

PMID- 7648345
TI  - Detection of lupus anticoagulants.

PMID- 7648344
TI  - Heterogeneity of antiphospholipid antibodies and their cofactors.

PMID- 7648346
TI  - Report of the First French Anticardiolipin Antibodies Standardization Workshop.

PMID- 7648348
TI  - Heart valve disease in systemic lupus erythematosus. Role of antiphospholipid
      antibodies.

PMID- 7648347
TI  - The antiphospholipid syndrome. Diagnosis, management, and pathogenesis.
AB  - Much more is known about the APLS than 15 yr ago, but more needs to be done.
      Clinically, major characteristics of the disorder have been defined, but the
      course of the disease and its relationship to other disorders, such as systemic
      lupus erythematosus (SLE), need to be defined. Good progress has been made in
      standardizing anticardiolipin and, to a lesser extent, LA. However, problems with
      interlaboratory and inter-assay variation need to be addressed. Doctors are
      getting a better idea of how to manage these patients with a view to preventing
      recurrences of thrombosis or pregnancy losses, but prospective studies are still
      desirable to give more definitive answers. Attention has turned to the
      pathogenesis of the disorder. It seems likely that antibodies mediate the
      clinical disorders with which they are associated, but the mechanisms by which
      this occurs still require further study.

PMID- 7648349
TI  - Physiopathology of thrombosis induced by antiphospholipid antibodies.

PMID- 7648350
TI  - Antimitochondrial antibodies in the antiphospholipid syndrome.

PMID- 7648351
TI  - Anti-beta 2-glycoprotein I antibodies and thrombosis.

PMID- 7648353
TI  - Evaluation of the obstetrical risks of the antiphospholipid syndrome and
      therapeutic management.

PMID- 7648352
TI  - Treatment of the antiphospholipid syndrome.

PMID- 7648354
TI  - Thermoreduction, a hypothesis for the origin of prokaryotes.
AB  - All thermophiles discovered so far are prokaryotes (Bacteria or Archaea).
      Furthermore, reconstructions of rRNA phylogenies suggest that the progenitor of
      all prokaryotes was a thermophile. These data are usually interpreted as
      supporting the hypothesis that all present day organisms, including eukaryotes,
      originated from hyperthermophiles. However, this scenario is difficult to
      reconcile with the RNA world theory, considering the instability of RNA at very
      high temperatures, and it is also contradicted by the finding of sophisticated
      devices for thermophilic adaptation in present day hyperthermophiles.
      Accordingly, I propose here 2 new hypotheses to explain the correlation between
      the procaryotic phenotype and thermophilic life without reference to a putative
      hot origin of life. Firstly, eukaryotes would be unable to live in thermophilic
      biotopes because of the susceptibility of their mRNA to degradation at high
      temperature. In prokaryotes, the absence of a nuclear membrane allows these
      organisms to bypass the problem of mRNA heat-induced hydrolysis by coupling
      transcription and translation. As a corollary of this first hypothesis, I also
      suggest that today prokaryotes might have originated from mesophilic ancestors
      via reductive evolution, in the process of adaptation to thermophily.

PMID- 7648355
TI  - [Demonstration of thermostable enzymes in thermophilic micro-organisms of
      hydrothermal origin].
AB  - During 3 cruises in the Pacific ocean, hydrothermal samples have been collected
      and some thermophilic bacteria and archaea have been purified. Four enzymatic
      activities have been screened on 77 chemo-organoheterotrophic thermophilic
      microorganisms. Forty-two isolates exhibited intracellular beta-glucosidase
      activity whereas only 7 (including only one archaeon) showed alcohol
      dehydrogenase one. Protease activity was not detected on only 6 isolates over 77.
      Twenty-seven isolates exhibited esterase activity and 3 different electrophoretic
      patterns have been revealed. No isolate was found to exhibit the 4 activities.
      Preliminary characterization of these activities showed high thermophily and
      thermostability, properties which could be used in potential biotechnological
      applications.

PMID- 7648356
TI  - [Cloning, characterization and expression of mouse ferritin L subunit gene].
AB  - We have cloned the functional gene coding for the L ferritin subunit by
      successive rounds of screening of a mouse genomic library using different
      oligonucleotides so as to avoid cloning the multiple pseudogenes of this rather
      complex multigene family. The L gene consists in 4 exons interrupted by 3 introns
      and spanning 1.8 kb. Quantitative measurements of H and L ferritin mRNA in
      various mouse tissues using a ribonuclease protection assay reveals important
      variations in the L/H ratio, the liver displaying the highest amount of L mRNA.
      Functional analysis of 1 kb of upstream sequence by transient transfections into
      the hepatoma cell line HepG2 shows that the mouse L gene transcription relies
      upon a minimal 130 bp promoter region containing 1 TATA box and 2 CCAAT motifs.
      Elements with an enhancing activity specific of hepatic tissue are likely to be
      located outside of this 1 kb fragment.

PMID- 7648357
TI  - [Demonstration of a specific profile of pathological Tau proteins in
      frontotemporal dementia cases].
AB  - We compared samples of different brain areas from patients with Alzheimer's
      disease (AD), progressive supranuclear palsy (PSP), controls subjects and from 4
      patients who met the clinical and pathological criteria for frontotemporal
      dementia (FTD), using a Western blot analysis. We used polyclonal antibodies
      directed against Tau proteins and the monoclonal antibody AD2 for the
      immunodetection of the pathological Tau proteins which are the basic components
      of neurofibrillary degeneration. In the PSP and AD cases, we respectively
      detected the abnormal Tau proteins 64 and 69 and the Tau proteins 55, 64, and 69,
      systematically associated with bands and smears, corresponding to catabolic
      products or aggregates of these abnormal Tau proteins. In FTD cases, the abnormal
      Tau proteins 55, 64 and 69 were also detected in the frontal and temporal poles
      from the autopsied case and in the cortical biopsies. However, the profiles were
      different because smears and proteolytics products of Tau proteins were absent.
      There was no detection of abnormal Tau proteins in control brain homogenates and
      in biopsies from patients with other neurodegenerative disorders such as
      spongiform encephalopathies or primitive gliosis. These results demonstrate that
      pathological Tau proteins are produced during FTD degenerating process, despite
      the absence of neurofibrillary lesions.

PMID- 7648358
TI  - [Determining of new karyotypes: value of a statistical method].
AB  - For the authors, Ectemnorrhininae (coleoptera, curculionidae) from Southern
      Indian Ocean islands constitute the subject of systematic karyological studies,
      in order to get further information as to the phylogeny of this group of insects.
      A previous study had been carried out about 3 different species, Ectemnorrhinus
      drygalskii, E. viridis and Dusmoecetes richtersi, through direct observation of
      the only few mitotic metaphase plates, completely isolated from each other, which
      could be found in adult testis squashes. But a new sort of technique is now
      available, and which involves a program of data statistical analysis, allowing
      the sorting out of objects which are characterized by 2 different parameters (in
      this case, the objects are chromosomes, defined by their length and centromeric
      index). So that almost all chromosomes can be fully examined in a given
      preparation, and this can be done in a standardized manner. Applying these new
      principles, a new determination of the mean values of the parameters
      characterizing the different chromosomes of the same 3 species is now being
      worked out. These values will be more accurently determined, and it will then be
      possible to compare such values, more efficiently, with those of other species of
      the same group when determined according to the same principles.

PMID- 7648359
TI  - A recurrent human papillomavirus integration site at chromosome region 12q14-q15
      in SW756 and SK-v cell lines derived from genital tumors.
AB  - The SW756 cell line, derived from an invasive cancer of the uterine cervix,
      harbours integrated human papillomavirus (HPV) 18 DNA sequences which have been
      located in chromosome band 12q13. By in situ hybridization experiments with
      tritiated and digoxigenin-labelled HPV18 probes on R-banded chromosomes, we now
      localize the integrated viral sequences in 12q14-q15. Interestingly, we have
      previously localized integrated HPV16 sequences in the same chromosomal region in
      SK-v cells, derived from a pre-invasive vulvar neoplasia. The chromosomal region
      12q14-q15 could thus correspond to a preferential site for the integration of HPV
      DNA in genital tumors.

PMID- 7648360
TI  - From the v-mpl oncogene to thrombopoietin.
AB  - v-mpl is a mouse oncogene that is part of the genome of the myeloproliferative
      leukemia virus (MPLV). The cellular homolog gene c-mpl encodes an hematopoietic
      cytokine receptor restricted to the megakaryocytic lineage of differentiation.
      Using the Mpl receptor protein, cDNAs corresponding to the receptor ligand were
      isolated in humans, pigs, dogs and mice. In vivo and in vitro, the recombinant
      molecule has both the thrombopoietin (TPO) and megakaryocyte-colony stimulating
      factor (MK-CSF) activities. This molecule (Mpl ligand/TPO/MK-CSF) is the humoral
      physiological regulator of platelet production.

PMID- 7648361
TI  - Solid malignant neoplasms after childhood irradiation: decrease of the relative
      risk with time after irradiation.
AB  - The pattern of the temporal distribution of solid cancer incidence after
      irradiation in childhood is not well known, although, its importance in
      radioprotection is well known. We studied a cohort of 1,055 children from 8
      European cancer centres, who received radiotherapy between 1942 and 1985 for a
      first cancer in childhood. After a mean follow-up of 19 years, 26 children
      developed a solid second malignant neoplasm (SMN), as compared to 5.6 expected
      from general population rates. Both the excess relative risk and the excess of
      absolute risk of solid SMN were higher among children who were younger at time of
      the irradiation. After reaching a maximum 15 to 20 years after irradiation, the
      excess relative risk of SMN decreased with time after irradiation, when
      controlling for age at irradiation and sex. The analysis of the risk of thyroid,
      brain and breast cancer together, as a function of the dose averaged on these 3
      organs lead to similar results.

PMID- 7648362
TI  - [Detection of cyclin A mRNA in intra-epithelial lesions of the anogenital tract
      induced by papillomavirus].
AB  - Human papillomaviruses (HPVs) have been recognized as likely viral agents
      responsible for anogenital precancer lesions and squamous cell cancers in both
      men and women. Nevertheless their role in carcinogenesis is not entirely clear.
      There are many other agents, both viral and non-viral, which might act
      synergistically or separately with HPV in a multistep tumorigenic process. Among
      non-viral factors, protooncogene and tumor suppressor gene alterations may be a
      major step towards the malignant transformation of an HPV-infected cell. The
      induction of unscheduled DNA synthesis and cell proliferation by human
      papillomaviruses would provide the basis for the potential of these viruses to
      contribute to the formation of tumors in vivo. Thus, we studied by in situ
      hybridization (ISH) the cyclin A gene expression in HPV-induced condylomatous and
      dysplastic lesions of the anogenital tract, and in inflammatory squamous
      intraepithelial tissues. We observed a high level of cyclin A gene expression in
      low grade squamous intraepithelial lesions infected by HPV type 6/11. Cyclin A
      induction was surprisingly more important in the upper third layers of
      differentiated cells together with large amounts of HPV DNA, than in
      proliferating basal and parabasal cells. An identical pattern was also shown in
      some low grade squamous intraepithelial lesions infected with potential oncogenic
      HPV. In contrast, there was evidence of low abundance cyclin A mRNA in most high
      grade squamous intraepithelial lesions induced by high risk HPV. In the
      inflammatory tissues, an ISH signal was sometimes detected in the basal cells. As
      for proliferating cell nuclear antigen (PCNA), these results observed in vivo
      reveal that viral oncoproteins are able to reactivate cellular DNA replication
      machinery to support papillomavirus DNA replication in normally differentiated,
      non-cycling cells. The induction of cyclin A gene expression appears to correlate
      with the proliferative rather than the transforming properties of these cells.

PMID- 7648363
TI  - [Demonstration of molecular forms of Rap 1 in cells or tissues deriving from
      normal or pathological human colonic epithelium].
AB  - Mutations of the cK-ras gene which confer oncogenic properties to the
      corresponding encoded small G protein, occur in 30 to 50% of the human colonic
      adenocarcinomas. Overexpression of Rap 1A, a member of the Ras family, in K-ras
      transformed fibroblasts, reverts the transforming properties of the oncogene.
      This indicates that Rap 1A may exert antagonistic properties towards the K-Ras
      protein. In this respect, we have been interested in comparing Rap 1 expression
      in the human adenocarcinoma cell line HT29 and in safe or pathological tissues
      deriving from the human colonic epithelium. In the human adenocarcinoma cells
      HT29, several immunoreactive forms of Rap 1 of 71 kDa, 47 kDa, 40 kDa and 24 kDa
      are detected. Extraction in Triton X-114 allows separation of HT29 cell proteins
      on the basis of their differential hydrophobic properties. Parallelly, proteins
      were separated in crude cytosolic or membrane fractions. Most of the
      immunoreactive material corresponding to the 24 kDa band may contain hydrophobic
      and membrane associated components. The molecular nature of the higher size
      components is also discussed here. In the tissues, the 47 kDa form which is
      common in all of the safe and pathological samples considered, appears to be
      specifically expressed in the colon. Besides, the 71, 68 and 24 kDa were found in
      pathological tissues. High expression of Rap 1 was demonstrated to be correlated
      with cell differentiation in the safe colonic epithelium and in the adenomas.
      Cloning of the Rap 1A cDNA is now in progress in the laboratory, using PCR
      detection in an HT29 expression library.

PMID- 7648364
TI  - [Yeast and the control of RAS by exchange factors].
AB  - Two isofunctional ras genes are present in the yeast Saccharomyces cerevisiae.
      Albeit their targets differ between mammals and yeast, they have conserved their
      regulators. The study of their positive regulators, guanine nucleotide exchange
      factors, have provided routes to the discovery of their regulatory elements in
      mammals. Ras are signal transducing proteins involved in the activation of the
      adenylate cyclase in yeast. They are activated by Cdc25p which has been shown to
      contain a Guanine Exchange Factor domain (GEF). SDC25, a gene partially
      homologous to CDC25, also contains a GEF domain but seems to be under a different
      regulation. It has been used to demonstrate the first guanine exchange activity
      on ras in vitro and was shown to be active by gene transfer in mammalian cells.
      Both Cdc25p and Sdc25p are associated to membrane and contain SH3 domains which
      are supposed to bind still unidentified proteins. Cdc25p is an unstable protein
      which contains a cyclin destruction box. Therefore activating effect on ras could
      be regulated by its level of expression. We have contributed to the isolation of
      a mammalian CDC25 homolog and we are analysing by directed mutagenesis key
      positions for ras activation of the human homolog HGRF55. That was performed by
      complementation analysis of yeast mutants as well as by use of two hybrid system.
      These approaches led us to the discovery of residues involved in ras interaction.

PMID- 7648366
TI  - [MAP kinase module: role in the control of cell proliferation].
AB  - A kinase cascade highly conserved throughout evolution, Raf/MAP kinase kinase
      kinase (MAPKKK)-->MAP kinase kinase (MAPKK)-->MAP kinase (MAPK)-->ribosomal S6
      kinase (p90 RSK), is thought to play a crucial role in signal transduction from
      the membrane to the nucleus. In mammalian cells, this cascade is connected both
      to tyrosine kinase receptors and G protein-coupled receptors. Although the mode
      of activation at the receptor level differs, all mitogens activate the
      ubiquitously expressed isoforms of MAPK, p42 and p44. We have cloned, epitope
      tagged and expressed in fibroblasts, the Hamster MAPKK and p44 MAPK in order to
      analyze their time-course of activation, their subcellular localization, their
      regulatory phosphorylation sites and their role in cell cycle entry. We have
      demonstrated that MAPK activation was rapid, biphasic and persistent. The
      sustained phase of activation is only obtained with potent mitogenic agents,
      correlating with their ability to elicit cell cycle entry. Activation of MAPKK is
      also rapid and persistent but does not distinguish between mitogenic and non
      mitogenic factors, indicating that a distinction occurs at the MAPK level,
      probably by the action of specific phosphatases such as MAPK phosphatase MKP-1.
      Both isoforms of MAPK are translocated into the nucleus upon growth factor
      addition whereas the upstream activators (MAPKKK, Raf and MAPKK) remain
      cytoplasmic. MAPK translocation, together with the ability of MAPK to
      phosphorylate transcription factors, indicates that MAPK might constitute a relay
      between cytoplasmic and nuclear events. Finally we show that interfering with the
      MAP kinase cascade, by expressing either MAPK antisense, a MAPK dominant negative
      mutant or the MAPK specific phosphatase, MKP-1, suppresses the growth factor
      induced G0 to G1 transition. In addition, permanently activated versions of MAPKK
      reduce growth factor requirement, allow autonomous cell growth and induce tumor
      formation in nude mice. We therefore conclude that MAP kinase activation is both
      necessary and sufficient to trigger cell cycle entry.

PMID- 7648365
TI  - [Mechanism of insulin action].
AB  - Insulin is a key hormone regulating glucose homeostasis. Its major target tissues
      are the liver, the skeletal muscle and the adipose tissue. At the cellular level,
      insulin activates glucose and amino acids transport, lipid and glycogen
      metabolism, protein synthesis, and transcription of specific genes. Insulin
      induced biological responses are mediated by a specific cell-surface receptor
      with tyrosine kinase activity. This receptor is a heterotetrameric protein
      consisting of two extracellular alpha subunits containing the ligand binding
      site, and two transmembrane beta subunits containing the hormone-sensitive
      enzymatic activity. The first step following insulin binding consists in receptor
      autophosphorylation on multiple specific sites and phosphorylation of cellular
      substrates. We will review the receptor structure, its mechanism of activation,
      and the autophosphorylation process. Two of the insulin receptor substrates have
      been identified as IRS-1 and Shc. IRS-1 is phosphorylated at several sites by the
      insulin receptor, and acts as a docking protein by associating several SH2
      containing proteins. One of these proteins is the p85 subunit of P13-kinase which
      is rapidly stimulated by insulin in adipocytes and skeletal muscle. The
      phosphorylated IRS-1 also associates Grb2, as does the phosphorylated Shc. This
      allows recruitment of the preformed complex Grb2-Sos to the plasma membrane. Sos
      is then capable of stimulating the Ras protein, which in turn activates Raf, the
      first element of the MAP-kinase cascade. The role of these proteins in insulin
      signalling will be discussed.

PMID- 7648367
TI  - [Has protein kinase CK2 a role in the intracellular mitogenic signalling?].
AB  - The protein kinase CK2 is an ubiquitous serine-threonine kinase found in all
      eukaryotic cells. Although well characterized on a biochemical ground, its role
      and regulation in the intact cell are not clearly understood. Its possible
      implication in the control of cell proliferation has been examined by several
      different approaches. (i) Immunocytochemical detection of CK2 revealed that
      whereas the signal was evenly distributed throughout cycle arrested cells in
      primary culture, it accumulates rapidly (30-90 min) in the nuclear compartment in
      cells stimulated to grow. (ii) CK2 biosynthesis is activated as an early response
      to growth factors in quiescent cells. The neo-synthesized kinase accumulates as
      the cells progress through the G1 phase. This growth factor-activated
      biosynthesis concerns in parallel the two kinase subunits. (iii) The kinase is
      activated in vitro by polyamines, which are increased in cells challenged by
      growth factors. Spermine binds to a specific domain of the beta subunit of CK2.
      (iv) In addition to phosphorylation CK2 forms a molecular complex with p53, a
      major negative regulator of the cell cycle. The complex was demonstrated in
      intact cells and reconstituted in vitro (Kd 70 nM) with purified components and
      shown to require the beta subunit and to result in the inhibition of p53 DNA
      annealing activity. These observations suggest that CK2 and p53 may play a
      coordinated role in the cell response to mitogenic stimuli.

PMID- 7648368
TI  - [RAS proteins and related proteins].
AB  - Since the mid-eighties, numerous small G-proteins of the ras gene superfamily
      have been identified and characterized; more than sixty members are distributed
      into four subfamilies: ras, rho, rab and ran. Although it appears that,
      structurally, the products of the ras superfamily are related and implicated in
      various and diverse intracellular mechanisms: signal transduction, cell cycle,
      differentiation, cellular traffic, etc., their true and specific functions and
      their scope and extent are still largely unknown for many of them. Approaches to
      unravel their function include: determination of their intracellular
      localization, differential expression in various cell and tissues, phenotypic
      changes induced by the active forms, studies of the interacting molecules. Recent
      studies combining advanced mammalian cell biology/biochemistry and genetic
      studies in yeast might help elucidate the specific role exerted by these
      proteins.

PMID- 7648369
TI  - [B-raf gene encodes for multiple isoforms with Mek-1 kinase activity].
AB  - The c-Rmil/B-raf proto-oncogene belongs to the mil/raf family encoding
      serine/threonine protein kinases shown to be involved in signal transduction from
      the membrane to the nucleus. We previously showed that the avian c-Rmil gene
      encodes two proteins of 94 and 95 kDa resulting from the alternative splicing of
      a 120 bp exon encoding 40 aminoacids (exon 10). We isolated from a mouse brain
      library B-raf cDNAs containing this exon 10 and a previously unidentified 36 bp
      insert which constitutes an additional alternatively spliced exon designated exon
      8b. These two exons are located between the CR2 region and the catalytic domain
      of the protein. By using specific sera generated against different regions of the
      B-Raf protein, we identified 10 B-Raf isoforms and we defined their structure and
      their expression pattern in adult mouse tissues. The B-Raf proteins are mainly
      expressed in neural tissues and, interestingly, isoforms containing aminoacids
      encoded by exon 10 are specifically expressed in these tissues. We also show that
      several B-Raf isoforms interact with the Mek-1 protein (MAP kinase kinase) and
      phosphorylate this protein on serine residues 218 and 222.

PMID- 7648370
TI  - [Cyclins and carcinogenesis].
AB  - Cell cycle progression is regulated by the sequential activation of cyclins
      expression and their association to the cyclin dependent kinases (CDK). Several
      in vitro and in vivo studies indicate that inappropriate cyclin expression
      (cyclins D, E, A) in the cell, whether or not due to chromosomal rearrangements,
      can participate in cell transformation. Thus these studies implicate cyclins in
      human carcinogenesis.

PMID- 7648372
TI  - Budesonide inhaled via Turbuhaler: a more effective treatment for asthma than
      beclomethasone dipropionate via Rotahaler.
AB  - BACKGROUND: Chlorofluorocarbon-propelled metered dose inhalers are facing a
      worldwide ban. Dry powder inhalers have been developed for the agents used in
      treatment of asthma. OBJECTIVE: Our objective was to compare the effects of two
      inhaled glucocorticosteroids in dry power inhalers: budesonide (delivered via
      Turbuhaler) and beclomethasone dipropionate (delivered via Rotahaler). METHODS: A
      randomized, crossover study with two steroid-treatment periods of 8 weeks. At the
      end of the study, the treatment with the inhaled steroid was stopped for 4 weeks.
      Sixteen adult patients with moderately severe asthma participated. Before the
      study all patients were treated with an inhaled steroid in a median dose of 0.60
      mg/day (range 0.15-0.80); during the study they received 0.20 mg twice daily.
      Peak expiratory flow rate was measured twice daily at home throughout the study,
      lung function was assessed every fourth week and airway responsiveness was
      measured before and after each period. Preference concerning efficacy and inhaler
      type was assessed at the end of the study. RESULTS: Twelve patients completed the
      study. Lung function, airway responsiveness, and symptoms deteriorated
      significantly in the steroid-free washout period; this period had to be shortened
      in 5/12 patients. Mean morning peak expiratory flow was significantly higher
      during budesonide treatment than during beclomethasone dipropionate treatment,
      the difference being 17 L/min (95% C.I.: 2-32 L/min, P = .026). Airway
      responsiveness improved 1.1 doubling concentrations after budesonide treatment,
      but decreased 0.3 doubling concentrations after beclomethasone dipropionate
      treatment. The difference between the values after budesonide and beclomethasone
      dipropionate treatment was 1.4 doubling concentrations (95% C.I.: 0.4-2.4
      doubling concentrations, P = .033). Forced expiratory flow in one second improved
      slightly more during budesonide than during beclomethasone treatment. The
      difference was 4.3% predicted (95% C.I.: -0.7-9.3%). Most patients reported
      budesonide Turbuhaler to be more effective (10 versus 0) and easier to use (11
      versus 1) than beclomethasone dipropionate Rotahaler. CONCLUSIONS: As a
      consequence of the difference in local potency of the steroids and the fact that
      Turbuhaler deposits more drug particles in the lung than Rotahaler, budesonide
      inhaled via Turbuhaler appeared to be a more effective steroid formulation than
      beclomethasone dipropionate inhaled via Rotahaler.

PMID- 7648371
TI  - [Stimulation of C-fos and jun B proto-oncogenes: potential role of TRH effects in
      clone cell line with prolactin (GH3B6)].
AB  - The hypothalamic neuropeptide TRH, which stimulates prolactin (PRL) release and
      PRL gene transcription, also raises c-fos proto-oncogene mRNA levels in GH3B6 rat
      pituitary cells. C-fos is assumed to be involved in the transduction of external
      signals to the nucleus as a component of AP1 transcription factor, a protein
      complex that contains a member of the jun proto-oncogene family. We have thus
      looked for the member(s) of the jun family that could be the partner of c-fos in
      TRH-stimulated GH3B6 cells. The common biphasic pattern of jun B and c-fos mRNA
      regulation under TRH exposure, i.e., an early peak and a long-lasting plateau
      phase, suggested that jun B was the best candidate. Then, to better understand
      the mode of action of TRH and to look for possible functions of c-fos and jun B
      in these cells, we have investigated the role of different intracellular
      signalings in the induction of each proto-oncogene. This was done taking as a
      model that the effects of TRH on PRL release and PRL gene transcription has been
      previously ascribed to the coupling of the TRH receptor to the activation of both
      protein kinase C- and calcium-dependent mechanisms. An extensive pharmacological
      analyses revealed that PKC-, Ca2+ but also protein kinase A-dependent mechanisms
      are involved in TRH-induced c-fos and jun B mRNA early responses in GH3B6 cells.
      The overall study also revealed specific features in the control by TRH of each
      proto-oncogene by some intracellular messengers. Finally, considering the fact
      that second long lasting phase of proto-oncogene expression was found associated
      with increased PRL mRNA accumulation whatever the stimulus, it might be proposed
      that AP1 [c-Fos/Jun B] factor could be involved in the regulation of PRL gene
      expression. Such hypothesis was furthermore supported by preliminary gel-shift
      experiments. Nevertheless, in view of the systematic coincidence between acute
      PRL release and early proto-oncogene induction, a role for c-fos and jun B in the
      control of genes involved in the secretory process might also be suggested.

PMID- 7648373
TI  - Lipoxygenase inhibitor-provoked acute asthma in a patient with asthma relieved by
      aspirin.
AB  - BACKGROUND: A very small number of patients with asthma show symptomatic
      improvement after administration of aspirin and other cyclooxygenase inhibitors.
      The clinical features of such patients with so-called aspirin-relieved asthma are
      similar to those with aspirin-induced asthma, but the pathogenesis is unclear.
      METHODS: We encountered one confirmed aspirin-relieved asthma patient and
      investigated the effects of cyclooxygenase and lipoxygenase inhibitors on his
      condition. RESULTS: Our patient showed a marked improvement of the forced
      expiratory volume in one second (FEV1) after administration of aspirin and three
      other cyclooxygenase inhibitors (indomethacin, mefenamic acid, and ketoprofen). A
      5-lipoxygenase inhibitor (AA861, Takeda, Japan), however, evoked acute asthma,
      and repeated administration of this drug resulted in some desensitization, but
      not complete tolerance. CONCLUSIONS: These results suggest an altered balance of
      arachidonic acid metabolism may play a critical role in the pathophysiology of
      aspirin-relieved asthma.

PMID- 7648374
TI  - Loratadine in the treatment of cough associated with allergic
      rhinoconjunctivitis.
AB  - BACKGROUND: Antihistaminic treatment of allergic asthma or cough-type asthma,
      including cough associated with allergic rhinocojunctivitis, has been recently
      reconsidered prospectively since new very potent compounds, nonsedating with anti
      allergic properties, are available. OBJECTIVE: The possible effectiveness of
      loratadine in the treatment of allergic cough was assessed in 20 patients with
      allergic rhinoconjunctivitis and cough due to Parietaria judaica during the
      pollen season (April to July 1993). METHODS: Allergic patients were enrolled in a
      double-blind, placebo-controlled, parallel-group, randomized study, and received
      loratadine 10 mg/d or placebo in oral tablets for 4 weeks. Occurrence and
      severity of conjunctival and nasal symptoms, severity and frequency of cough
      attacks were assessed daily by the patients together with peak expiratory flow
      evaluation performed twice a day, ie, in the morning and in the evening.
      Physicians evaluated conjunctival and nasal signs, and spirometry on admission
      (before treatment), 2 and 4 weeks after treatment. On admission methacholine
      challenge was also performed to assess PD20. Pollen counts were assessed during
      the study. RESULTS: According to patients' diary cards, ocular and nasal symptoms
      were progressively reduced by loratadine treatment (respectively P < .05 and P <
      .01), as well as cough frequency (P < .05) and cough intensity (P < .01). Peak
      expiratory flow rate, forced vital capacity, and forced expiratory volume in one
      second significantly decreased in the placebo-treated group (P < .01), while they
      were not modified in loratadine-treated patients, who remained normal.
      CONCLUSIONS: The study suggests that loratadine may be beneficial in the
      treatment of allergic cough, as well as in rhinoconjunctivitis. Further studies
      of this may be warranted.

PMID- 7648375
TI  - Food-induced and occupational asthma due to barley flour.
AB  - BACKGROUND: Occupational exposure to inhalant allergens may induce asthma but the
      presence of asthma after the ingestion of the allergen is rarely reported.
      OBJECTIVE: To clarify the clinical relevance of every identified allergen in a
      patient with respiratory symptoms after exposure to feeding stuffs and cereal
      flours in his work environment and after ingestion of beverages made of these
      cereal grains. METHODS: Case report. Skin prick tests and serum-specific IgE (CAP
      FEIA-fluoroenzymeimmunoassay) were used in order to identify specific IgE
      antibodies. Bronchial provocation tests were performed as an aid in determination
      of clinical relevance of occupational exposure to the patient's asthma. RESULTS:
      A 50-year-old man developed bronchial asthma both after exposure to feeding
      stuffs and flours and after ingestion of beverages made of cereal flours. Allergy
      to storage mites (Lepidoglyphus destructor), house dust mites (Dermatophagoides
      pteronyssinus and farinae), and barley and corn flours were demonstrated by skin
      testing and serum-specific IgE. Bronchial challenge tests with every allergen
      showed no response except for an immediate response to barley flour. The most
      relevant clinical feature was an immediate asthmatic response developed after
      oral provocation with either barley-made beer or barley flour itself which
      indicates IgE-mediated, food-induced bronchial asthma (sulfite sensitivity was
      ruled out). CONCLUSION: In some particular cases, barley flour may induce
      bronchial asthma through inhalational and oral routes due to an IgE-mediated
      mechanism.

PMID- 7648376
TI  - Selective deficiency in pneumococcal antibody response in children with recurrent
      infections.
AB  - BACKGROUND: Impaired ability to respond to polysaccharide capsular antigens of
      Streptococcus pneumoniae may be associated with an IgG subclass deficiency and
      recurrent respiratory infections. OBJECTIVE: To identify children over three
      years of age with recurrent otitis media, sinusitis, or pneumonia who had low or
      absent pneumococcal antibody titers as their sole manifestation of immune
      deficiency and to determine their response to the 23-valent pneumococcal vaccine.
      RESULTS: Of 100 children with low pneumococcal antibody titers, 87 generated a
      protective antibody response to the pneumococcal vaccine (> 300 ng/mL to the
      majority of the antigen serotypes), while 13 responded poorly or not at all.
      Repeated vaccination of nonresponders failed to produce a normal response.
      CONCLUSION: We have identified two clinically distinct subpopulations of children
      with recurrent respiratory infections characterized by their responsiveness to
      pneumococcal antigens: one group did not respond to pneumococcal vaccination,
      whereas the other group responded both clinically and serologically. The
      nonresponding 6.5% subpopulation has an apparent isolated defect in anti
      pneumococcal antibody production associated with recurrent respiratory infections
      despite normal IgG2 subclass levels.

PMID- 7648377
TI  - IgE-dependent reactions to urologic catheter extracts by skin testing in latex
      allergic patients.
AB  - BACKGROUND: Latex allergy is mediated by residual IgE-binding proteins found on
      latex products. While most reported reactions involve latex gloves, the
      allergenic potential of other latex containing devices is unknown. OBJECTIVE: To
      assess the allergenic potential of latex urologic catheters. METHODS: Two
      identical lots of urologic catheters were extracted in sterile saline and
      analyzed for latex protein content using sensitive ELISA and Western blot assays.
      The extracts were tested by skin prick testing in a population of 47 latex
      allergic patients. RESULTS: Latex proteins were detected by ELISA assay, however,
      the Western Blot method was not sensitive enough to measure latex proteins in
      these catheter extracts. Skin prick testing using a standard latex reagent
      (Bencard) demonstrated the test population to be extremely sensitive to latex as
      68% of the population reacted to a 1/100,000 dilution. Using undiluted catheter
      extracts, only 11% of these latex-allergic patients reacted to catheter lot A and
      2% to catheter lot C, by prick skin test. Eight percent of the control patients
      had a positive latex prick skin test and none reacted to the catheter extract.
      CONCLUSIONS: The data suggest that processing and leaching of these specific
      latex urologic catheters resulted in a very low latex allergen content. The low
      prevalence of skin test reactivity in a population of latex-allergic patients
      suggests that these catheters would be an unusual cause of allergic reactions. It
      is not possible, however, to determine whether latex-allergic patients could
      safely use latex urologic catheters.

PMID- 7648379
TI  - Analysis of meteorologic variables and seasonal aeroallergen pollen counts in
      Denver, Colorado.
AB  - BACKGROUND: The observation of low levels of weed pollens following a freeze and
      an early autumn snowfall in Denver, Colorado led to this analysis of meteorologic
      variables and pollen counts. OBJECTIVE: The purpose of this study was to examine,
      in depth, the relationship between observed pollen counts and a selection of
      independent meteorologic variables. METHODS: We prospectively studied in 1991
      daily high and low temperature, relative humidity, precipitation, barometric
      pressure, percent sunshine, wind velocity and direction, tree, grass, and weed
      pollen, as well as dates of the first frost/freeze. Similar data were
      retrospectively analyzed for 1987-1990. RESULTS: Correlation coefficients for the
      prospective data were as high as .611 for high temperature and cottonwood and
      .718 for high temperature and maple (P < .001). High and low temperature showed
      strong correlations with the combined weed counts (.598 and .628, respectively, P
      < .001). CONCLUSIONS: Denver weed pollens appear impacted more by temperature and
      less by precipitation and humidity, while the converse is true for tree and grass
      pollen. However, weed pollen, especially sage, may appreciably rebound after
      freezing temperatures. While separate meteorologic variables may have high
      correlations with specific pollen counts in a given year, such effect is not
      consistent and varies from year to year.

PMID- 7648378
TI  - Longitudinal assessment of bone mineral density in children with chronic asthma.
AB  - BACKGROUND: With the emphasis on asthma as a chronic inflammatory process, the
      management of moderate to severe asthma, even in the pediatric population, has
      shifted to the regular use of inhaled anti-inflammatory agents, including inhaled
      corticosteroids. Accompanying the use of these agents has been the precaution
      that long-term use may have subtle or potential side effects, including growth
      suppression or decreased bone mineral deposition. OBJECTIVE: We sought to study
      the effects of inhaled anti-inflammatory agents on bone mineral density
      accumulation in growing asthmatic children. Included in this report is the
      longitudinal acquisition of bone mineral density in children with moderate to
      severe asthma. METHODS: Bone mineral density in normal and asthmatic children was
      measured longitudinally by dual-energy absorptiometry. Bone densitometry was
      determined twice over a 7- to 16-month period in 21 asthmatic children and a 13-
      to 60-month period in 14 normals. These children with two longitudinal visits
      were compared with a group of 107 normal children who had a single bone mineral
      density measurement. RESULTS: Nineteen of 21 asthmatic children used regular
      inhaled corticosteroids during the interval visits. The majority of the asthmatic
      boys had bone mineral density measurements, at both visits, that were at a higher
      percentile than normal boys with two visits. Asthmatic girls had bone density
      measurements at percentiles not significantly different than normal girls with
      two visits. CONCLUSIONS: The advancement of bone mineral density in asthmatic
      children provides support for the safety of inhaled anti-inflammatory medications
      on bone mineral density in children with significant asthma.

PMID- 7648380
TI  - Biopharmaceutic characteristics of a new extended-release theophylline
      formulation (Uni-Dur).
AB  - BACKGROUND: There is a close relationship between improvement in airway function
      and the plasma concentration of theophylline, as well as between rapidly rising
      plasma theophylline concentrations and increased frequency of undesired effects.
      Development of pharmaceutical formulations and prescribed dosage intervals for
      theophylline dosage forms should therefore be directed toward providing the most
      stable plasma concentrations attainable. OBJECTIVE: To characterize the steady
      state biopharmaceutic profile of Uni-Dur following once-daily or twice-daily
      administration. METHODS: Twenty-four adult male volunteers with average
      theophylline clearance (3.0 and 5.5 L.h-1) received three treatments on separate
      occasions: Uni-Dur 800 mg once-daily, Uni-Dur 400 mg twice-daily, and Uniphyl 800
      mg once-daily. Treatments were taken after a meal for five days with at least 1
      week washout between treatment periods. Trough blood samples were collected prior
      to the AM dose on days 3, 4, and 5, and at specified intervals up to 48 hours
      after the AM dose on day 5 for subsequent determination of theophylline
      concentrations in plasma. RESULTS: The area under the plasma concentration-time
      curve (AUC; microgram.mL-1.h) for theophylline over 24 hours on day 5 was 187 for
      Uni-Dur 800 mg once-daily, 187 for Uni-Dur 400 mg twice-daily, and 172 for
      Uniphyl 800 mg once-daily; the peak plasma concentrations were 10.4, 9.4, and
      11.0 micrograms.mL-1 and the trough concentrations were 5.5, 7.2, and 3.5
      micrograms.mL-1, respectively; fluctuation index (peak minus trough divided by
      trough) was 78%, 16%, and 231%, respectively. No further accumulation of
      theophylline occurred after day 3. No serious nor severe adverse events were
      reported during any treatment. CONCLUSIONS: Uni-Dur is an extended-release
      formulation that provides stable plasma concentrations of theophylline over a 24
      hour period with less fluctuation than observed with a once-daily reference
      formulation. In subjects with normal theophylline clearance, Uni-Dur administered
      twice-daily provided remarkably stable theophylline plasma concentrations over a
      24-hour period. Absorption of theophylline from Uni-Dur was not affected by food,
      and no evidence of dose-dumping was observed. Uni-Dur should provide efficacious
      theophylline therapy with minimal adverse events in patients with symptoms of
      asthma and reversible bronchospasm associated with chronic bronchitis and
      emphysema.

PMID- 7648381
TI  - IFN-gamma activates superoxide anion production in blood monocytes from allergic
      asthmatic patients.
AB  - BACKGROUND: Peripheral blood monocytes may participate in allergic diseases by
      releasing inflammatory mediators. We have recently shown enhancement of
      nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) oxidase activity in
      adherent human peripheral blood monocytes from allergic patients when
      immunoglobulin E (IgE) binds to its low affinity receptor. Interferon-gamma (IFN
      gamma), a monocyte-activating lymphokine, has been shown to prime monocytes for
      superoxide anion release. OBJECTIVE: We hypothesized that IFN-gamma could
      directly activate blood monocyte superoxide anion release and evaluated its
      modulatory effect on IgE-induced superoxide anion release from those cells.
      METHODS: Seven patients with allergic asthma, 6 patients with allergic rhinitis,
      and five nonallergic controls were studied. We measured superoxide anion release
      from their blood monocytes using a chemiluminescence assay. Cells were either
      nonstimulated, or stimulated for 30 minutes with IFN-gamma and/or serum IgE.
      RESULTS: We found that IFN-gamma stimulated superoxide anion production and
      decreased the IgE-induced superoxide anion production after 30 minutes of IFN
      gamma preincubation only in blood monocytes from patients with allergic asthma.
      CONCLUSIONS: These data suggest that IFN-gamma receptors may be increased and/or
      coupled to NADPH oxidase in allergic asthmatic patients.

PMID- 7648383
TI  - The beta 2-agonist controversy revisited.
AB  - OBJECTIVE: The goal of this review is to summarize the present controversy
      surrounding the safety of beta 2-agonists in the treatment of asthma. This
      article presents a brief summary of questions and issues related to (1) increased
      mortality, (2) morbidity, (3) airways reactivity, and (4) tolerance. DATA
      SOURCES: References are limited to the English language and extend back to the
      late 1960s. Articles included are based on clinical experience in humans. STUDY
      SELECTION: Papers were selected on the basis of being representative of the four
      controversial issues regarding beta 2-agonists presented in this review. RESULTS:
      Analysis of the available data regarding the use of inhaled beta 2-agonists does
      not support the existence of major adverse effects. Inconsistencies both within
      and between published reports preclude identification of a recognizable pattern
      of adverse effects associated with use of these drugs. The argument that beta 2
      agonists, as a class, have caused an increase in asthma mortality is weak.
      Fenoterol alone, due to its formulation and marketing position, may have been
      associated with asthma deaths because it was used more frequently in patients
      with unstable and difficult-to-control asthma. The Canadian studies suggesting a
      class effect do not reconcile with negative findings around the world. Purported
      evidence of increased asthma morbidity associated with regular use of beta 2
      agonists is unconvincing due to problems with the analyses, the small physiologic
      changes observed, and the lack of confirmation of loss of asthma control in other
      studies using similar designs. There also are no convincing data that beta 2
      agonists unfavorably modulate bronchial responsiveness in patients with asthma or
      reduce the protection to constrictor stimuli in a clinically meaningful way.
      CONCLUSIONS: beta-Agonists have been used for more than 30 years to treat and
      prevent asthma, yet the controversy over the safety of these drugs has surfaced
      only occasionally during this period. A careful review of the data should result
      in the conclusion that beta 2-agonists remain an appropriate and reliable
      treatment option for patients with asthma.

PMID- 7648382
TI  - Goals of asthma therapy.
AB  - OBJECTIVE: The purpose of this article is to facilitate the management of
      patients with asthma. The article will discuss the components of optimal care and
      asthma therapy. DATA SOURCES: References are limited to the English language.
      Also included are descriptions of experiences based on the clinical practice of
      the author. STUDY SELECTION: Papers were selected on the basis of their
      timeliness, explanation of important findings related to clinical practice, and
      the treatment of asthma. RESULTS: Effective asthma management requires
      understanding of asthma pathophysiology and how and when to provide asthma
      treatment, which includes specific, symptomatic, and adjunctive therapies.
      Optimal care entails a thorough knowledge of the goals of asthma therapy,
      including preventing asthma symptoms, maintaining nearly normal pulmonary
      function and activity levels, preventing asthmatic exacerbations, and avoiding
      adverse effects from asthma medications. For patients with an allergic component
      to their disease, allergen avoidance and immunotherapy can cure or at least
      significantly improve a patient's asthma. Using an "Asthma Action Plan," patients
      can be instructed on how to prevent symptoms of asthma from occurring and how to
      maintain normal or nearly normal pulmonary function by monitoring their pulmonary
      function "zone," based on daily peak flow meter results. At the present time,
      asthma is treated inadequately in the United States, but the situation can be
      improved primarily through education. CONCLUSIONS: The goals of asthma therapy
      are achievable in the US if several objectives are met: physicians are taught
      asthma pathophysiology; patients are educated about the prevention and treatment
      of asthma; the importance of an evaluation by an allergist is recognized; and
      patients are provided access to good medical care.

PMID- 7648384
TI  - Pharmacology of long-acting beta-agonists.
AB  - BACKGROUND: When first developed more than 30 years ago, beta-agonists (eg,
      isoproterenol) did not discriminate between beta 1- and beta 2-subtypes of the
      beta-adrenoceptor, resulting in effective bronchodilation but also unwanted
      extrapulmonary side effects. Albuterol later became the prototype selective beta
      2-agonist--well tolerated and highly effective in controlling bronchospasm. The
      major drawback of these more selective beta 2-agonists, however, was their short
      duration of action (four to six hours). This problem has been largely overcome
      with the development of a new generation of long-acting beta 2-agonists
      represented by salmeterol and formoterol (not currently available in the US).
      This paper summarizes the mechanism of action, potency and receptor selectivity,
      onset and duration of action, and bronchodilator and nonbronchodilator activity
      of these long-acting beta 2-agonists. SUMMARY: Preclinical studies have shown
      both salmeterol and formoterol to be potent and selective at beta 2-adrenoceptors
      but to have different mechanisms and durations of action. The pharmacologic
      profiles of these drugs result from prolonged activation of beta 2-adrenoceptors,
      leading to long-lasting bronchodilation (with no evidence of tolerance or
      tachyphylaxis) and additional nonbronchodilator properties. The long-acting beta
      2-agonists represent a therapeutic advance in the management of asthma.

PMID- 7648387
TI  - Management of acute severe asthma.
AB  - OBJECTIVE: This review presents a consensus on the emergency management of adult
      asthma. Management is discussed under six headings: assessment, asthma treatment,
      supportive treatment, complications, precipitating cause, and
      disposition/followup; the first four are undertaken concurrently. DATA SOURCES:
      The framework for this review is the 1994 "Guidelines for Emergency Management of
      Adult Asthma" produced by the Canadian Association of Emergency Physicians in
      collaboration with the Canadian Thoracic Society. This document is supported by
      144 English language references in humans. STUDY SELECTION: Papers were selected
      to emphasize the major points of consensus. About 25% of the above references
      were included in the bibliography. RESULTS: Rapid assessment of the severely ill
      asthmatic patient must include objective features: vital signs, pulsus paradoxus,
      oxygen saturation, and expiratory flow rates. Asthma therapy should commence
      immediately with inhaled beta 2 agonist and systemic or ingested corticosteroid;
      inhaled anticholinergic is added initially or as early second-line treatment.
      Supportive treatment includes oxygenation, fluid-electrolyte balance, and
      nonpharmacologic relief of anxiety. When necessary, mechanical ventilation
      allowing "permissive hypercapnia" using low peak airway pressure (low volume and
      slow inspiratory flow rate) reduces the risk of barotrauma; the PaO2 and pH are
      maintained while allowing PaCO2 to rise. Early recognition and treatment of
      complications, especially pneumothorax, can be life-saving. Identification of
      precipitating factor(s) occasionally dictates initial therapy (anticholinergic
      for beta blocker-induced bronchospasm, epinephrine for asthma accompanying a
      systemic allergic reaction), but is most important as the first step to
      preventing future episodes. Disposition should be based on objective measurement
      of flow rates. CONCLUSION: Aggressive rapid management of severe asthma by these
      or similar guidelines should improve morbidity and mortality.

PMID- 7648386
TI  - Allergen extract standardization: reality, myth, or dream?

PMID- 7648388
TI  - An unusual case of asthma with onset late in life.

PMID- 7648389
TI  - Exposing the immunology of naked DNA vaccines.

PMID- 7648385
TI  - Long-acting beta 2-agonist salmeterol compared with albuterol in maintenance
      asthma therapy.
AB  - BACKGROUND: Salmeterol is the first long-acting inhaled bronchodilator available
      in the United States. This paper summarizes the combined results of the two
      pivotal US studies evaluating the efficacy of this beta 2-agonist in the
      maintenance treatment of asthma. METHODS: Salmeterol (42 micrograms twice daily)
      was compared with the short-acting beta 2-agonist albuterol (180 micrograms four
      times daily) in two double-blind, randomized studies involving 556 patients with
      mild-to-moderate asthma. All patients could use supplemental inhaled albuterol as
      needed for breakthrough symptoms, and patients were allowed to continue to use
      inhaled corticosteroids during the study. RESULTS: Salmeterol, 42 micrograms bid,
      was more effective than albuterol, 180 micrograms qid, or placebo in maintaining
      bronchodilation, as measured by FEV1 over 12-hour periods and morning and evening
      peak expiratory flow rates. Patients who received salmeterol also experienced
      significantly greater increases in the number of days without asthma symptoms and
      the percentage of nights without awakenings compared with either the albuterol or
      placebo group. There was no difference between patients who received concomitant
      inhaled corticosteroids and those who did not with respect to pulmonary-function
      measurements or improvements in symptoms. There was no loss of asthma control
      with salmeterol over the 12-week period. CONCLUSIONS: Salmeterol, 42 micrograms
      twice daily, was more effective than albuterol, 180 micrograms four times daily,
      or placebo (plus as-needed albuterol) in improving pulmonary function and
      controlling asthma symptoms.

PMID- 7648390
TI  - T cells in inflammatory bowel disease: protective and pathogenic roles.

PMID- 7648391
TI  - Tissue-regulated differentiation and maturation of a v-abl-immortalized mast cell
      committed progenitor.
AB  - An immature v-abl-transformed mast cell line (V3-MC) was derived from a mouse
      that developed systemic mastocytosis after transplantation of v-abl-infected bone
      marrow cells. V3-MCs injected intravenously into adult BALB/c mice infiltrated
      the liver, spleen, and intestine by day 6 and underwent progressive
      differentiation and maturation, eventually resembling indigenous mast cells. In
      terms of their protease content, the V3-MCs that localized in the liver and
      spleen differed from those in the intestine, and both differed from the cultured
      V3-MCs. The acquired expression of certain proteases and the loss of expression
      of other proteases in these tissue V3-MCs defines particular phenotypes and
      indicates that the differentiation and maturation of mast cell-committed
      progenitor cells are primarily regulated by factors in the different tissue
      microenvironments.

PMID- 7648393
TI  - DM enhances peptide binding to class II MHC by release of invariant chain-derived
      peptide.
AB  - Major histocompatibility complex (MHC) class II molecules bind antigenic peptides
      rapidly after biosynthesis in antigen-presenting cells (APCs). By contrast, the
      rate of peptide binding to purified class II molecules is remarkably slow. We
      find that purified HLA-DR molecules bind peptides rapidly in the presence but not
      the absence of HLA-DM, a recently identified heterodimer required for efficient
      antigen processing. The same effect is seen with immunoprecipitated DM,
      suggesting that DM interacts directly with DR. Class II-associated invariant
      chain peptides (CLIP) are selectively and rapidly released from DR during
      incubation with DM at pH 5. We conclude that DM is a cofactor that enhances
      peptide binding to DR molecules through a mechanism involving peptide exchange.

PMID- 7648394
TI  - Regulation of thymocyte development through CD3: functional dissociation between
      p56lck and CD3 sigma in early thymic selection.
AB  - We studied the extent of functional linkage between CD3 sigma and p56lck in pre
      TCR-dependent thymocyte development. Differentiation of DN to DP cells was
      examined by treatment of RAG2/CD3 sigma and RAG1/p56lck double-deficient mice
      with anti-CD3 epsilon antibodies. The results suggest that CD3 sigma has no
      specific role in this maturation step, but may be important for amplification of
      signaling through the pre-TCR. In contrast, p56lck is the main protein tyrosine
      kinase associated with signaling through the pre-TCR-CD3 complex. In DP
      thymocytes, the Ca2+ response to anti-CD3 epsilon was totally abolished in CD3
      sigma-I-but only reduced in p56lck-I-mice, and in vivo responses to anti-CD3
      epsilon differed from one another. Thus, CD3 sigma and p56lck are functionally
      not tightly associated and their deficiencies cause distinct developmental
      defects.

PMID- 7648392
TI  - Multiple binding sites for bacterial superantigens on soluble class II MHC
      molecules.
AB  - We used surface plasmon resonance to study the binding of a set of soluble mouse
      I-E class II major histocompatibility molecules, each occupied by a different
      single peptide, to the staphylococcal enterotoxin superantigens, SEA and SEB. The
      rates of association and dissociation to SEA varied greatly depending on the I-E
      bound peptide. By contrast, binding to SEB yielded fast association and
      dissociation rates, which were relatively peptide independent. The results also
      indicated nonoverlapping binding sites for SEB and SEA on class II and raised the
      possibility of enhanced SAg presentation to T cells by cross-linking of cell
      surface class II.

PMID- 7648395
TI  - A direct physical association between ETS and AP-1 transcription factors in
      normal human T cells.
AB  - The Ets and AP-1 families of transcription factors bind distinct DNA elements and
      subserve diverse functions in multiple lymphoid and nonlymphoid cell types.
      Functionally important Ets and AP-1 binding sites have been identified in a large
      number of enhancer elements, suggesting important cooperative interactions
      between these two families of transcription factors. In this report, we have
      demonstrated a direct physical interaction between Ets and AP-1 proteins both in
      vitro and in activated human T cells. This interaction is mediated by the binding
      of the basic domain of Jun to the Ets domain of Ets proteins. Jun, in association
      with Ets, is capable of interacting with Fos family members to form a
      trimolecular protein complex. The physical association between Ets-1 and AP-1
      proteins is required for the transcriptional activity of enhancer elements
      containing adjacent Ets and AP-1 binding sites. We conclude that direct physical
      interactions between Ets and AP-1 transcription factors play an important role in
      regulating mammalian gene expression.

PMID- 7648398
TI  - Nuclear receptors for 1,25-dihydroxy-22-oxavitamin D3 (OCT) and 1,25
      dihydroxyvitamin D3 in gastric gland neck mucous cells and gastrin
      enteroendocrine cells.
AB  - 22-Oxacalcitriol the analog with low calcemic effect and the original hormone
      1,25(OH)2 vitamin D3 were localized by autoradiography in mouse stomach at
      different time intervals after intravenous injection. Both compounds showed a
      distinct nuclear concentration and retention in neck mucous cells of gastric and
      pyloric glands, and in dispersed endocrine cells in the antrum region. When the
      nuclear binding of radioactively labelled compound was compared between gastric
      neck cells and duodenal absorptive cells, binding was low but sustained in neck
      cells. Peak uptake after the injection was between 8 and 12 h in neck cells, but
      between 15 min and 30 min in duodenal villous epithelium. In the duodenum, weak
      nuclear labelling appeared at 8 h and was undetectable at 12 h under the
      conditions of the experiment. Nuclear labelling of neck cells remained detectable
      at 12 h and even after 24 h, similarly for both OCT and 1,25(OH)2 vitamin D3.
      These results suggest that the stomach is an important target tissue for vitamin
      D and its analog OCT. Regulation of neck cell functions is suggested, such as
      proliferation and differentiation of surface epithelium and gastric gland
      epithelium, and neck cell secretion of acidic mucus. Regulation is also indicated
      of G-cell gastrin secretion associated with gastrin paracrine effects on parietal
      cell HCl and intrinsic factor secretion, chief cell pepsinogen secretion, neck
      cell proliferation, as well as endocrine effects on systemic calcium homeostasis.

PMID- 7648396
TI  - Isolation of mutant T lymphocytes with defects in capacitative calcium entry.
AB  - Calcium and calcium-binding proteins play important roles in the signaling
      cascade leading from the initial engagement of TCRs on T cells to the fully
      activated state. To undertake a molecular dissection of this cascade, we first
      isolated a Jurkat T cell line derivative containing the NF-AT promoter element
      driving transcription of the diphtheria toxin A chain gene (dipA), resulting in
      rapid cell death. Selecting viable cells that fail to activate NF-AT-dependent
      transcription, we isolated two independent cell lines possessing defects in
      capacitative Ca2+ entry. NF-AT-dependent transcription can be restored in these
      cells by expression of a constitutively active calcineurin, but not
      overexpression of the Ca2+ regulatory protein CAML, which can normally replace
      the Ca2+ signal. The defect in these cell lines probably lies between CAML and
      calcineurin in the T cell activation cascade.

PMID- 7648399
TI  - Immunohistochemical identification of adrenomedullin in human, rat, and porcine
      tissue.
AB  - The histological localization was investigated of adrenomedullin (AM), a novel
      vasorelaxant peptide originally isolated from human pheochromocytoma. The
      immunohistological distribution was examined of AM in human, rat, and porcine
      tissues using a polyclonal antibody to a fragment comprising C-terminal amino
      acids 40-52 of human adrenomedullin [AM(40-52)NH2]. Almost all of the human
      pheochromocytoma and normal adrenal medullary cells of all three species were
      immunostained and found to be intensely positive for AM. Furthermore, AM
      immunoreactive cells were present in the pancreatic islets, gastrointestinal
      neuroendocrine system, anterior pituitary, and choroid plexus with some degree of
      interspecies heterogeneity. These findings indicate that AM-immunoreactive cells
      are widely distributed in the endocrine and neuroendocrine system, suggesting
      that AM plays some important role in the control of systemic and local
      circulation and also of humoral secretion.

PMID- 7648397
TI  - Activation of HIV expression by CD30 triggering in CD4+ T cells from HIV-infected
      individuals.
AB  - CD30 is a member of the tumor necrosis factor receptor superfamily,
      preferentially expressed by T cells producing type 2 helper (Th2) cytokines,
      whose ligand (CD30L) has been identified on B cells, activated macrophages, and a
      subset of activated T cells. We show here that cross-linking CD30 with an
      agonistic CD30-specific monoclonal antibody, as well as with CD30L+ CD8+ T cell
      clones or CD30L+ B cells, enhanced HIV replication in CD4+ T cells from HIV
      infected individuals, and such a potentiating effect was inhibited by anti-CD30L
      antibody. The anti-CD30L antibody also exerted a suppressive effect on
      spontaneous HIV replication occurring in lymph node cells from an HIV-sero
      positive patient, showing CD30L expression by both B and CD8+ T lymphocytes.
      Thus, CD30 triggering by CD30L-expressing cells may plan an important role in the
      activation of HIV expression from latently infected CD4+ T cells.

PMID- 7648401
TI  - Non-hazardous organic solvents in the paraffin-embedding technique: a rational
      approach. Aliphatic monoesters for clearing and dewaxing: butyldecanoate.
AB  - The aim of this study was to substitute hazardous compounds, used in tissue
      processing and dewaxing, with compounds having lowest possible toxicity and
      inflammability without impairing the morphology, staining characteristics, or
      diagnostic value of the tissue sections. All aromatic compounds and aliphatic
      hydrocarbons (e.g. alkanes, isoparaffins, petroleum distillates, etc.) were
      rejected, primarily due to their high vapour pressure. Based on a theoretical
      study of compounds used for clearing, a number of non-hazardous potential
      substitutes were chosen. The following experimental study narrowed the group to
      three unbranched, saturated, aliphatic monoesters containing 12-14 carbon atoms.
      On large-scale testing of these compounds, we found butyldecanoate to be the
      closest to an ideal substitute for aromatic and aliphatic hydrocarbons in the
      histology department: the section quality is at least equal to that obtained with
      xylene. For dewaxing, it is used at 30-35 degrees C. Butyldecanoate is not
      suitable as a pre-mounting agent. In practice, this is no problem as modern
      mounting agents permit mounting of coverslips directly from ethanol without
      impairing the appearance of the section in the microscope. Butyldecanoate has
      only a slight odour, insignificant vapour pressure (< 0.01 kPa at 20 degrees C),
      and does not present a fire hazard (flash point 134 degrees C). The introduction
      of this compound in the laboratory poses no health hazard, and the substance is
      biodegradable.

PMID- 7648400
TI  - Protein kinase C isoenzymes in mouse harderian gland. Differential expression of
      the alpha- and epsilon-isoforms during pregnancy. Protein kinase C-OC.
AB  - Protein kinase C (PKC) is known to be involved in the regulation of exocytosis in
      different cell lines and tissues. Experiments were designed to determine whether
      the Harderian gland of CD-1 mouse produces PKC isoenzymes and whether the
      expression of the isoforms changes during pregnancy. The presence of the
      isoenzymes was assessed by immunoblotting experiments using extract of total
      Harderian gland and polyclonal antisera specific for nine different PKC isoforms.
      Antisera giving a positive staining on Western blots were subsequently used for
      immunohistochemical investigation using a secondary antibody conjugated to
      alkaline phosphatase. Immunoblotting experiments revealed that the Harderian
      gland from female mouse expresses PKC isoforms-alpha, -epsilon, -zeta and -eta.
      These isoforms were also detected in the Harderian gland from 13-day pregnant
      mouse; however, striking quantitative changes were seen concerning the alpha- and
      epsilon-isoforms. The 80-kDa native from of PKC-alpha almost doubled in the
      pregnant mouse in comparison with normal female mouse whereas the amount of 50
      kDa catalytic domain did not change. Protein kinase C-epsilon appeared as a 92-
      to 93-kDa form and a 67-kDa form. While the 92- to 93-kDa protein was expressed
      to a similar extent in both types of mouse, the 67-kDa form was more abundant in
      the Harderian gland from normal female mouse. These data were corroborated by
      immunohistochemical experiments and showing a diffuse and granular staining of
      the adenomeres. These observations demonstrate for the first time (to our
      knowledge) that the mouse Harderian gland produces several PKC isoenzymes that
      could be involved in the regulation of exocytosis and/or other
      functions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7648403
TI  - Distribution of E-cadherin and Ep-CAM in the human lung during development and
      after injury.
AB  - Paraffin sections were obtained of human fetal, adult, and pathological lung
      (pulmonary fibrosis after radiotherapy or chemotherapy). The localization of
      epithelial adhesion molecules E-cadherin and Ep-CAM (former epithelial surface 40
      kDa glycoprotein) was investigated by immunoperoxidase and/or immunofluorescence
      techniques with monoclonal antibodies. During development, the epithelia of the
      primary pulmonary primordium, the secondary bronchi and the adult bronchial
      epithelium retained immunoreactivity for E-cadherin and Ep-CAM with lateral
      immunostaining of cell membranes. In normal adult lungs, Ep-CAM was detected in
      type I and II alveolar epithelial cells, whereas E-cadherin was confined to the
      basolateral domain of type II cells. In pulmonary fibrosis, Ep-CAM could be
      further detected on the cell surface of epithelial remnants. In contrast, E
      cadherin expression was characterized by a change of the membrane localization to
      a spotty, cytoplasmic pattern in the alveolar epithelium, possibly indicating
      functional inactivation of the protein during fibrogenesis.

PMID- 7648402
TI  - Immunostaining of a heterodimeric dermatan sulphate proteoglycan is correlated
      with smooth muscles and some basement membranes.
AB  - A heterodimeric 760-kDa dermatan sulphate proteoglycan tentatively named PG-760
      was characterized as a product of keratinocytes, endothelial cells, and
      fibroblasts. The two core proteins of 460 kDa and 300 kDa are linked by
      disulphide bridges, and both carry one or only very few dermatan sulphate chains.
      Different antisera against PG-760 were used in the present study to investigate
      the distribution in selected murine tissues by light and electron microscopy. PG
      760 immunostaining was observed in cornea (epithelium including basement
      membrane, stroma, and Descemet's membrane), skin, mucosa of the small intestine,
      Engelbreth-Holm-Swarm (EHS)-tumour (matrix and cells), and the smooth muscle
      layers of uterus, small intestine, and blood vessels. No staining was observed in
      capillaries, striated muscles, and liver parenchyma including the central vein.
      The expression of PG-760 in EHS-tumour was also demonstrated after extraction
      with 4 M guanidine and partial purification by diethylaminoethyl (DEAE)
      chromatography. We conclude that this novel proteoglycan exhibits a unique tissue
      distribution being a constituent of some but not all basement membranes, of some
      other extracellular matrices, and additionally, of all investigated smooth muscle
      layers.

PMID- 7648404
TI  - Localization of dihydroorotate oxidase in myocardium and kidney cortex of the
      rat. An electron microscopic study using the cerium technique.
AB  - Biochemical studies have demonstrated that dihydroorotate dehydrogenase
      (DHOdehase; EC 1.3.3.1 or 1.3.99.11) is the sole enzyme of de novo pyrimidine
      synthesis in mitochondria, whereas the rest of the pathway takes place in the
      cytosol. The dehydrogenation of dihydroorotate to orotate is linked to the
      respiratory chain via ubiquinone. In this study, we show for the first time the
      ultrastructural localization of DHOdehase. Since the purified enzyme was found to
      act both as dehydrogenase and as oxidase, the cerium capture technique for
      detecting enzymatically generated hydrogen peroxide could be applied to pin-point
      the in situ activity of DHOdehase oxidase in mitochondria of rat heart and kidney
      cortex. Cerium perhydroxide as the final reaction product was detected
      predominantly in the matrix with some focal condensation along the inner
      membrane, but not in the intermembrane space. From this pattern of localization,
      it is concluded that the active site of the membrane-bound enzyme could face the
      mitochondrial matrix similar to succinate dehydrogenase. The reliability of the
      applied method for the demonstration of DHOdehase oxidase was demonstrated by the
      addition of Brequinar sodium to the incubation medium. This quinoline-carboxylic
      acid derivative is a potent inhibitor of DHOdehase and has proven anti
      proliferative activity. The present observations do not ascertain whether the
      oxidase is permanently active as a constant portion of the enzyme in vivo,
      similar to xanthine oxidase/dehydrogenase. However, DHOdehase should be
      considered as a source of radical oxygen species under pathophysiological
      conditions.

PMID- 7648405
TI  - Predominant periportal expression of the fructose 1,6-bisphosphatase gene in rat
      liver: dynamics during the daily feeding rhythm and starvation-refeeding cycle.
AB  - Expression of the gene of the key gluconeogenic enzyme fructose 1,6
      bisphosphatase (FBPase) was studied in rat liver during the daily feeding cycle
      and during refeeding after starvation. Total abundance of FBPase mRNA could be
      quantified by Northern blotting analysis with a digoxigenin-labelled 40-mer
      oligonucleotide probe. The zonal localization could not be demonstrated by in
      situ hybridization under several varied conditions with the 32P-end-labelled
      oligonucleotide probably due to insufficient sensitivity but was demonstrated
      with a 35S-labelled cRNA probe; the latter was synthesized from a polymerase
      chain reaction (PCR)-amplified 751 bp cDNA fragment inserted into a pBluescript.
      During a normal 12:12 h day/night rhythm (darkness with feeding from 1900 to 0700
      hours), the total amount of FBPase mRNA stayed almost the same throughout the
      whole day. After 60 h of starvation the FBPase mRNA level decreased from a
      maximum at 1800 hours by approximately one-third at the end of refeeding at 0700
      hours. Both during the normal feeding rhythm, after 60 h of starvation and during
      refeeding, i.e. under all conditions, FBPase mRNA was predominantly distributed
      in the periportal zone. The results clearly show that the preferentially
      periportal distribution of the FBPase enzyme activity is controlled mainly at a
      pretranslational level.

PMID- 7648406
TI  - Muscarinic receptors in the prenatal mouse embryo. Comparison of M35
      immunohistochemistry with [3H]quinuclidinyl benzylate autoradiography.
AB  - Muscarinic cholinergic receptors are widespread in nervous tissue and smooth
      muscle or paracrine epithelial cells of various organs. In the embryo, muscarinic
      receptors are transitorily expressed in the early blastoderm and later on in
      blastemic tissues during morphogenesis. Recently, a monoclonal antibody (M35)
      against muscarinic receptor from calf brain became available. In the present
      study the use of M35-immunohistochemistry is compared to autoradiographic
      localization of muscarinic binding sites in the mouse embryo. The aim of the
      study is to test the suitability of the antibody for localization of muscarinic
      receptors in embryonic tissues. For autoradiography whole-body sagittal cryostat
      sections of the 17- and 18-day mouse embryo were covered with LKB-Ultrofilm after
      incubation with the radioactive ligand [3H] quinuclidinyl benzylate (QNB). For
      immunohistochemistry cryostat sections of formalin fixed tissues were used. In
      general, all tissues exhibiting ligand binding were also recognized by the
      antibody. M35-immunohistochemistry resulted in higher spatial resolution of
      receptor localization than [3H]QNB autoradiography. Definitive muscarinic
      receptors were observed in smooth muscle and the epithelial lining of the
      vasuclar, intestinal, respiratory and urinary system, in the brain, spinal cord
      and peripheral nerves. The embryonic type of the muscarinic receptor was detected
      in the mesothelium of lung and liver, in the nephrogenic blastema of the
      metanephros, and in lung mesenchyme. A large amount of embryonic muscarinic
      receptors was found in the remnants of the notochord and in the nucleus pulposus
      of the developing vertebral column. A function in morphogenesis is discussed of
      the embryonic muscarinic receptor.

PMID- 7648407
TI  - Immunolocalization of the neural cell adhesion molecule L1 in non-proliferating
      epithelial cells of the male urogenital tract.
AB  - The localization of the neural cell adhesion molecule L1 in the male urogenital
      tract (including seminal vesicles and prostate) of the mouse and bull was
      investigated using immunocytochemical and immunochemical methods in order to
      better understand the function of this glycoprotein in non-neural tissues. L1
      antibodies labeled non-myelinated nerves in all portions of the urogenital tract
      investigated. However, L1 immunoreactivity was also found between epithelial
      cells of several regions of the urogenital system including epididymal tail,
      deferent duct, ejaculatory duct and seminal vesicles. Some L1 immunoreactivity
      was also demonstrated between epithelial cells of murine urinary bladder and
      urethra. The specificity of the immunoreaction was verified by western blots.
      There was no correlation between L1 expression and proliferating activity as
      revealed by double immunocytochemistry using various markers of cell
      proliferation. This unexpected expression of L1 in nonneural tissues is mainly
      restricted to non-proliferating epithelia of those portions of the urogenital
      tract that are derived from the Wolffian duct. It is suggested that L1 in these
      epithelia could enhance the mechanical resistance and reduce transepithelial
      permeability.

PMID- 7648409
TI  - The dental health of single male hostel dwellers in Leeds.
AB  - Attitudes and behaviour towards oral health among 104 homeless men in Leeds were
      assessed at interview. Of these, 101 agreed to a subsequent dental examination.
      The findings confirmed a high level of normative need despite a low level of felt
      need. Appointments were offered at two local community dental clinics, but the
      majority of men failed to attend. Appropriate provision of dental care is
      discussed and recommendations made for future developments.

PMID- 7648408
TI  - Dental anxiety, utilisation of dental services, and DMFS status in Norwegian
      military recruits.
AB  - The aim of the study was to assess the association between dental anxiety, oral
      health (evaluated by clinical and radiographic examinations), and utilisation of
      dental services. Results from correlation and regression analyses confirmed the
      generally held expectation that high dental anxiety would be associated with
      poorer oral health measured as numbers of decayed or filled surfaces.
      Significant, but weak, relationships were found between dental anxiety and
      utilisation measures, i.e. number of dental visits during the last year and time
      since last dental visit. Taken together, the data indicated that dental anxiety
      was a facet of more general negative oral health/preventive oral health related
      behaviour. Thus, high scores on this dimension were characterised by high dental
      anxiety, more oral health problems, inadequate dental attendance, slightly less
      frequent toothbrushing and larger intake of sweet soft drinks. However, the study
      also demonstrated that non-selected dentally anxious individuals as a group did
      not exhibit the almost complete avoidance pattern typical of patients seeking
      special treatment for dental fear. Even in the subgroup with particularly high
      dental anxiety, several individuals reported having been to the dentist during
      the last one or two years.

PMID- 7648410
TI  - The knowledge and attitude of Hong Kong secondary school teachers and students
      towards HIV infection and dentistry.
AB  - Although human immunodeficiency virus (HIV) infection and acquired immune
      deficiency syndrome (AIDS) are firmly entrenched in Hong Kong no data are
      available on the knowledge and attitudes of Hong Kong secondary school teachers
      and teenage children towards this infection, and their perception of infection
      control measures currently undertaken by the dental profession to prevent such
      infectious diseases. Hence a postal questionnaire survey of a total of 2,886
      teenagers and 372 school teachers of 21 secondary schools in Hong Kong was
      conducted. The questionnaire comprised a total of 13 questions divided into two
      categories; the first, aimed at assessing the respondents' general knowledge and
      attitudes towards AIDS, and the second related to AIDS, dentistry and infection
      control. More than half of the students and one quarter of the teachers surmised
      that HIV infection is equivalent to developing AIDS. Although the great majority
      of the respondents (85-97 per cent) were aware that HIV can not be transmitted
      through sharing combs and meals, one in two teachers and one in three students
      thought that the virus could be transmitted through saliva. A large majority of
      respondents believed television to be the most, and dentists the least,
      informative source on AIDS out of a list of eight options. Approximately one half
      of both groups were concerned about contracting HIV infection during dental
      treatment and 65 per cent of students and 57 per cent of teachers thought that
      dentists did not have sufficient knowledge to identify AIDS patients. Finally,
      more than three quarters of the respondents thought that it would be ill-advised
      to visit a dentist treating HIV-infected patients.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7648411
TI  - Measuring health behaviours.

PMID- 7648412
TI  - The Government's reforms for NHS dentistry.

PMID- 7648413
TI  - Adult dental surveys: a different approach.
AB  - Traditional surveys of adult dental health have used calibrated examiners to
      collect clinical data. This study examines an alternative approach using data
      collected by general dental practitioners about their adult patients. Twenty-four
      dentists in Greater Manchester recorded both personal and intra-oral information
      on 3,832 of their regularly attending dentate patients over 24 years of age. The
      mean numbers of filled teeth, sound teeth and the proportion of patients with 21
      or more teeth were all similar to those found in the 1988 United Kingdom national
      survey of adult dental health. For example, the mean number of filled teeth in
      the 25-34 year age group was 11.7 compared with 11.9 for subjects who claimed to
      attend regularly in the 1988 national survey, and these figures reduced to 11.2
      and 10.0 in the 55-64 year age group. The proportion of adults with 21 or more
      teeth was found to be 99 per cent compared with 98 per cent in the 1988 survey
      for the 25-34 year age group, falling to 55 per cent compared with 56 per cent in
      the 55-64 year age group. The collection of epidemiological data by general
      dental practitioners is feasible, and has construct and internal validity. It is
      a possible alternative to conventional surveys of adult dental health.

PMID- 7648414
TI  - Public health aspects of third molar surgery. The effect of surgeons' treatment
      thresholds on efficiency and effectiveness.
AB  - Disease associated with third molars is being recognised increasingly as a public
      health problem in terms both of rising incidence and of appropriate use of
      resources. Since minor alterations in treatment philosophy can have a substantial
      impact on the efficiency and effectiveness of oral surgery services, this study
      examines the sensitivity and specificity of oral surgeons' decisions and uses
      Receiver Operator Characteristics (ROC) analysis to investigate their ability to
      detect and make appropriate judgements about teeth which need extraction
      according to established criteria. The study shows that the seniority of the
      surgeon making the treatment decisions had no significant effect on the decisions
      made and also demonstrated wide variations between the treatment plans made by
      individual clinicians. It is clear from this study that if an efficient and
      effective service for the treatment of third molar disease is to be commissioned,
      policy decisions about criteria for intervention must be made by health service
      purchasing authorities, adhered to by secondary care providers, and shared with
      the primary care practitioners who refer patients for treatment.

PMID- 7648415
TI  - Methodological issues involved in sampling a population of the elderly for a
      dental survey.
AB  - A random sample of adults over 60 years of age was drawn from three different
      areas of England to take part in a survey of their dental status and needs. The
      paper describes sampling methods and operational problems in trying to measure
      oral health in such an age group. The local Family Health Services Authority
      lists, based on registrations with general medical practices, were used as
      sampling frames. These proved to be straightforward to manipulate and are
      believed to be almost complete for the population at this age. Final samples of
      around 800 individuals in each area were visited at home, representing 53-62 per
      cent of all subjects who could be contacted, except in one subgroup where only 39
      per cent of contacts permitted a visit. There were problems related to difficulty
      making contact with a proportion of the names sampled. This may have resulted
      from list errors, illnesses and unrecorded changes of address. A letter from the
      subjects' family doctors appeared to be an important factor influencing response
      rates. Systematic bias among subjects refusing a visit was assessed using a
      follow up postal questionnaire which showed that the edentulous were under
      represented in the final (visited) sample by 1-10 per cent, whilst the dentate
      non-attenders were under represented by 2-13 per cent.

PMID- 7648416
TI  - Characteristics of participants and non-participants in annual mass screening for
      oral cancer in 60-year-old residents of Tokoname city, Japan.
AB  - Three thousand one hundred and twenty three 60-year-old residents of Tokoname
      city, Japan, were eligible to take part in an ongoing annual mass screening
      programme for oral cancer and precancer during the years 1986-1990. All received
      a mailed questionnaire to ascertain details of their personal circumstances,
      lifestyle factors and medical history. One thousand six hundred and sixty eight
      (53 per cent) responded and of these, 347 plus an additional 89 non responders,
      totalling 14 per cent of the sample, subsequently attended for screening. Those
      screened were significantly more likely than non participants to have taken part
      in other general health or cancer screening, to report past histories of diseases
      or conditions with severe subjective symptoms and to have access to the screening
      facility on foot, by bicycle or by car. There were no significant differences
      between the groups in their smoking habits or alcohol consumption. Ways of
      improving compliance in screening are considered and in particular, the need for
      further strengthening the complementary public education programme to increase
      its effectiveness is highlighted.

PMID- 7648417
TI  - Self-perception of malocclusion among adolescents.
AB  - This study investigated the self-perception of malocclusion among 506 15 and 16
      year-old children. The Aesthetic Component of the Index of Orthodontic Treatment
      Need was used to allocate each subject to 'no aesthetic need' for treatment,
      'borderline aesthetic need', or 'definite aesthetic need' for treatment
      subgroups. The results indicate that adolescents who were scored by a trained
      examiner (using IOTN) as having similar dental aesthetics have similar
      perceptions of their malocclusion irrespective of their gender or social
      background.

PMID- 7648418
TI  - The pattern of caries in a group of 5-year-old children and in the same cohort at
      9 years of age.
AB  - A group of 1,006 children examined at 5 years of age was followed up after a
      further four year period. Thirty seven per cent of the group had some caries
      experience at the age of 5 years. Four years later this proportion had increased
      to 52 per cent. There was little caries in incisor teeth at the age of 5 with the
      disease affecting mainly primary molars, (especially second primary molars) and
      occlusal surfaces. Primary molars continued to experience new attack in the
      subsequent four years, with lesions affecting more first primary molars and more
      approximal than occlusal surfaces during this period. New caries was seen most
      often in children with previous disease experience but children with a lower dmfs
      of between 1 and 5 at 5 years experienced a similar increment to those with more
      extensive caries (dmfs > or = 6). In contrast, few lesions were seen in the
      children who had been caries free at 5 years. Children in the study had taken
      part in a trial of a lower fluoride toothpaste (550ppmF) especially formulated
      for young children. There was no difference in relative pattern of disease in
      test and control groups but the trend seen at the end of the trial for children
      who had used the test paste to have slightly higher levels of disease than those
      who had used a standard control paste (1,055ppmF) was seen again four years
      later.

PMID- 7648419
TI  - Clusterin: physiologic and pathophysiologic considerations.
AB  - Clusterin is a heterodimeric glycoprotein produced by a wide array of tissues and
      found in most biologic fluids. A number of physiologic functions have been
      proposed for clusterin based on its distribution and in vitro properties. These
      include complement regulation, lipid transport, sperm maturation, initiation of
      apoptosis, endocrine secretion, membrane protection, and promotion of cell
      interactions. A prominent and defining feature of clusterin is its induction in
      such disease states as glomerulonephritis, polycystic kidney disease, renal
      tubular injury, neurodegenerative conditions including Alzheimer's disease,
      atherosclerosis, and myocardial infarction. The expression of clusterin in these
      states is puzzling, from the specific molecular species and cellular pathways
      eliciting such expression, to the roles subserved by clusterin once induced. This
      review will discuss these physiologic and pathophysiologic aspects of clusterin
      and speculate on its role in disease.

PMID- 7648420
TI  - Oxidative damage to mitochondrial DNA and its relationship to ageing.
AB  - Mitochondria are the most important intracellular source of reactive oxygen
      species and are protected against them by enzymatic and nonenzymatic
      antioxidants. Nevertheless, mitochondrial DNA (mtDNA) is subject to severe
      oxidative damage, and much more so than nuclear DNA (nDNA). Damage is indicated
      by the detection of various base modifications, particularly 8
      hydroxydeoxyguanosine (8OHdG), which can lead to point mutations because of
      mispairing. MtDNA is also fragmented to some extent. Conceivably, such
      fragmentation relates to the deletions found in mtDNA. Several hypotheses suggest
      that defective mitochondria contribute to, or are responsible for, ageing. Recent
      observations indicate that mitochondria in an old organism differ in many
      respects from those in a young organism. Thus, with ageing there is an increased
      production of reactive oxygen species, a decrease in certain antioxidants, a
      decreased transcription, translation, and cytochrome oxidase content, and an
      increase in the extent of DNA modifications. Major unresolved questions
      concerning the role of mtDNA changes in ageing are addressed: is there a causal
      relationship; what is the true extent of DNA damage; what are significance and
      functional consequences of mtDNA oxidation; are reactive oxygen species the cause
      of the DNA modifications found in vivo; what is the relationship between DNA
      damage and alterations of RNAs and proteins? Future studies promise to clarify
      the possible causal relationship between mitochondrial dysfunction, reactive
      oxygen species production, mtDNA modifications, and ageing.

PMID- 7648421
TI  - The uptake and metabolism of cystamine and taurine by isolated perfused rat and
      rabbit lungs.
AB  - Cystamine has been reported to be taken up and metabolized to taurine by the rat
      lung slices. The objectives of the present study were to compare the uptake and
      metabolism of cystamine and taurine in isolated perfused lungs of rats and
      rabbits and examine the action of glutathione (GSH) on these processes. The
      uptake and metabolism of [14C]cystamine and [14C]taurine were studied at 20
      microM concentrations each in isolated, ventilated, perfused rat and rabbit
      lungs. In some experiments, 1 microM GSH was included in the perfusate prior to
      the addition of cystamine. The perfusate and lung homogenate samples were
      analyzed for cystamine and its metabolites. [14C]cystamine uptake with and
      without GSH was 13 and 14% in rat lungs and 37 and 32% in rabbit lungs.
      [14C]taurine uptake was 10% in rat and 37% in rabbit lungs. The levels of
      radiolabeled cystamine and its metabolites were (nmol/g lung): 20.0 +/- 10.0 and
      11.5 +/- 7.0 cystamine, 4.7 +/- 0.5 and 3.2 +/- 0.5 hypotaurine and 56.0 +/- 16.0
      and 49.4 +/- 6.0 taurine, for rat and rabbit lungs, respectively, when perfused
      without GSH; and 18.0 +/- 1.0 and 2.5 +/- 0.5 cystamine, 6.6 +/- 0.5 and 18 +/-
      10 hypotaurine and 60.0 +/- 12.0 and 33.6 +/- 9.0 taurine, when perfused with
      GSH, for rats and rabbit lungs, respectively. Taurine did not undergo any further
      metabolism in either of the lungs. These studies show that cystamine is taken up
      and metabolized to taurine via hypotaurine by both rat and rabbit lungs in a
      manner similar to that seen in rat lung slices. However, rat lungs have much
      greater capacity to metabolize cystamine to taurine than rabbit. Inclusion of GSH
      did not significantly alter the ability of lungs to sequester cystamine from the
      perfusate but the metabolism of hypotaurine to taurine was markedly decreased in
      rabbit lungs. Taurine was not metabolized any further. It is concluded that rat
      and rabbit lungs take up cystamine from the systemic circulation, metabolize it
      via hypotaurine to taurine, and effuse most of the latter in to the circulation.

PMID- 7648422
TI  - Electron spin resonance studies of fatty acid-induced alterations in membrane
      fluidity in cultured endothelial cells.
AB  - Endothelial cell dysfunction has been implicated in the development of
      atherosclerosis. Of vital importance to the maintenance of endothelial cell
      integrity is the preservation of membrane functional and structural properties,
      such as membrane fluidity. The aim of this study was to develop a model for
      studying the relationship between endothelial cell integrity and membrane
      fluidity alterations in a well-defined cell culture setting. Alterations in
      membrane fluidity were assessed using electron spin resonance after labeling
      endothelial cells with the lipid-specific spin labels, CAT-16 and 12-nitroxide
      stearic acid. Endothelial cells were exposed to various 18-carbon fatty acids,
      i.e. stearic (18:0), oleic (18:1), linoleic (18:2), or linolenic (18:3), in
      addition to lipolyzed HDL (L-HDL) and benzyl alcohol. Membrane phospholipid fatty
      acid composition of endothelial cells supplemented with these fatty acids was
      analyzed using gas chromatography. All fatty acids, except 18:0, decreased
      membrane fluidity. A relationship between membrane fluidity and fatty acid
      compositional alterations in cellular phospholipids was observed. In particular,
      the arachidonic acid content decreased following exposure to 18:1, 18:2, or 18:3.
      Exposure of endothelial cells to L-HDL, lipoprotein particles which contain high
      levels of 18:1 and 18:2, also decreased membrane fluidity. The stabilization of
      cytoskeletal actin filaments by phalloidin partially prevented 18:2-induced
      increases in albumin transfer, thus implicating a cytoskeletal involvement in the
      18:2-induced membrane fluidity changes involved in endothelial cell dysfunction.
      The present study shows that the exposure of endothelial cells to various lipids
      causes membrane fluidity alterations which may contribute to endothelial cell
      dysfunction and atherosclerosis.

PMID- 7648423
TI  - Identification of a component of the sea urchin hyaline layer, HLC-175, which
      undergoes proteolytic processing during development.
AB  - To define the role(s) played by the sea urchin extraembryonic matrix, the hyaline
      layer, we have previously purified and characterized a number of the protein
      components of this structure. We are currently studying the timing and
      significance of the proteolytic processing of these species. The localization of
      HLC-175 in the egg and 1-hr-old embryo was determined by indirect
      immunofluorescence analysis. The relationship between HLC-175 and the 109- and 81
      kDa species was determined by a combination of native gel electrophoresis, sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) under non-reducing
      conditions and protein gel blot analyses using the anti-175, -109 and 81 kDa
      antisera. Using gel exclusion chromatography we have fractionated a mixture of
      proteins extracted from the surface of 1-hr-old sea urchin embryos. A set of
      fractions eluting from the column contained three species of apparent molecular
      masses 175-, 109- and 81 K. These species comigrated on analysis by either non
      reducing SDS-PAGE or native gel electrophoresis. Inclusion of the reducing agent,
      dithiothreitol, in the solubilizing solutions abolished comigration of these
      polypeptides. When polyclonal antisera were prepared against each of these
      antigens cross-reactivity between the 175- and 109 kDa species and between the
      175- and 81 kDa species was detected. Developmental protein gel blot analyses
      revealed a precursor-product relationship between the 175- and the 109- and 81
      kDa polypeptides. Indirect immunofluorescence analysis confirmed the localization
      of HLC-175 to the hyaline layer. The results reported here clearly identify HLC
      175 as a component of the hyaline layer.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7648424
TI  - Effect of dietary antioxidants on puromycin aminonucleoside nephrotic syndrome.
AB  - Several studies indicate the pathophysiological importance of reactive oxygen
      species in rats with nephrotic syndrome induced by puromycin aminonucleoside, an
      experimental model of the human minimal change disease. The role of reactive
      oxygen species in these rats was further evaluated, examining the effect of
      dietary deficiency and supplementation of antioxidants (vitamin E and selenium)
      on biochemical and renal ultrastructural alterations induced by puromycin
      aminonucleoside. Male Wistar rats, weaned at 3 weeks, were placed on diets
      normal, deficient or supplemented in vitamin E and selenium for 4 weeks. At the
      end of this period, rats were divided in two groups: control (sacrificed without
      any further treatment) and nephrotic (injected with puromycin aminonucleoside and
      sacrificed 7 and 22 days later). In control rats, the dietary deficiency or
      supplementation of antioxidants resulted in no significative differences in renal
      function, proteinuria or kidney ultrastructure. However, kidney lipoperoxidation,
      kidney glutathione peroxidase activity and circulating levels of vitamin E
      changed according to the amount of antioxidants in the diet. Seven days after the
      injection of puromycin aminonucleoside, rats fed normal, deficient or
      supplemented diets, developed nephrotic syndrome. However, proteinuria,
      hypoproteinemia, renal dysfunction and ultrastructural alterations were higher in
      rats fed a deficient diet. In contrast, proteinuria and kidney ultrastructural
      alterations were lower in rats fed a supplemented diet. Kidney lipoperoxidation
      and glutathione peroxidase activity increased on day 7 in rats fed a normal or a
      deficient diet, but not in rats fed a supplemented diet. This study shows that
      nephrotic syndrome induced by puromycin aminonucleoside in rats is modified by
      dietary antioxidants (vitamin E and selenium). Dietary supplementation
      ameliorates it and dietary deficiency exacerbates it.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7648425
TI  - Interactions of Solutol HS 15 and Cremophor EL with plasma lipoproteins.
AB  - Two emulsifying agents, Solutol HS15 and Cremophor EL, were compared with regard
      to their effects on human plasma lipoproteins in vitro and on mouse plasma
      lipoproteins in vitro and in vivo. Both agents promoted binding of a hydrophobic
      photosensitizing agent (C8KC) to a circulating plasma species of low bouyant
      density. Persistence of this material was greater with Cremophor than with
      Solutol. Experiments carried out with labeled Solutol indicated that the vehicle
      itself is a component of this new species. High concentrations of either vehicle
      ( > or = 0.06%) led to decreased electrophoretic mobility of human LDL and HDL in
      vitro. In the mouse, a different effect was observed, resulting in complex
      changes in electrophoretic mobility of plasma lipoproteins. The plasma half-life
      of C8KC in the circulation of the mouse was correlated with the persistence of an
      altered electrophoretic lipoprotein pattern. Since Solutol and C8KC showed
      similar half-lives, this result suggests that the plasma half-life of the
      sensitizer is correlated with the persistence of the vehicle. While Solutol and
      Cremophor were designed to be vehicles for drug formulation, they also influence
      persistence of some drugs in the circulation.

PMID- 7648426
TI  - Antileukemic activity of 4-pyranone derivatives.
AB  - In a search for new compounds possessing antitumor activity, we examined the
      effects of a group of oxygen containing heterocyclic derivatives on L1210 murine
      leukemia cell growth. Several 5-hydroxy-2-hydroxymethyl-4-pyranone derivatives
      were tested in a growth assay employing a human leukemia K562 cells line. IC50
      was extrapolated from the growth inhibition curves at compound concentrations
      ranging from 0.1 to 100 microM. The halogen derivatives of 5-hydroxy-2
      hydroxymethyl-4-pyranone inhibited L1210 cell growth in suspension culture after
      96 hr incubation in the following order: 5-hydroxy-2-iodomethyl-4-pyranone (IC50
      3.15 microM) > 6-bromo-2-bromomethyl-5-hydroxy-4-pyranone (IC50 3.40 microM) > 6
      bromo-5-hydroxy-2-hydroxy-methyl-4-pyranone (IC50 3.75 microM) > 2-bromomethyl-5
      hydroxy-4-pyranone (IC50 4.30 microM) > 5-benzyloxy-2-chloromethyl-4-pyranone
      (IC50 5 microM) > 6-bromo-2-chloromethyl-4-pyranone (IC50 13.50 microM) > 6
      chloro-2-chloromethyl-5-hydroxy-4-pyranone (IC50 18 microM) > 2-chloromethyl-5
      hydroxy-4-pyranone (IC50 20 microM). The compound, 5-hydroxy-2-hydroxymethyl-4
      pyranone has no effect on L1210 cell growth. These results suggest that 5-hydroxy
      2-hydroxymethyl-4-pyranone derivatives might represent a new class of compounds
      with antileukemic activity.

PMID- 7648427
TI  - The effects of various kinase and phosphatase inhibitors on the transmission of
      the prolactin and extracellular matrix signals to rabbit alpha S1-casein and
      transferrin genes.
AB  - In all species, milk protein genes are specifically expressed in the mammary
      gland under the control of lactogenic hormones and extracellular matrix. In
      rabbit, casein gene expression is induced by prolactin alone and this induction
      is amplified by extracellular matrix. Transferrin gene expression is induced by
      extracellular matrix in the absence of hormones. The transduction mechanisms of
      prolactin and extracellular matrix to milk protein genes is only partly known.
      The present study has been undertaken to determine if protein kinases and
      phosphatases are involved in these mechanisms. Rabbit primary mammary cells were
      cultured in three different conditions (i) directly on floating collagen I, (ii)
      on plastic after a trypsinization to remove endogenous extracellular matrix, and
      (iii) on floating collagen I after a trypsinization to restore a functional
      extracellular matrix. In these culture conditions, prolactin and several protein
      kinase and phosphatase inhibitors were added to the medium. The expression of
      alpha S1-casein and transferrin genes was evaluated using Northern blotting
      analysis. In cells cultured directly on collagen I, staurosporine, quercetin and
      6-dimethylaminopurine strongly inhibited prolactin action of alpha S1-casein gene
      whereas herbimycin A was only partly inhibitory. An erbstatin analogue, tyrosine
      phosphate, 1(5 isoquinolylsulphonyl) 2-methylpiperazine and GF 109 203 X did not
      alter prolactin action. The inhibitors which inhibited prolactin action when
      cells were directly cultured on collagen I were also those which prevented the
      induction of alpha S1-casein gene expression when cells were cultured on plastic
      in the absence of extracellular matrix. The induction of transferrin gene by the
      extracellular matrix was inhibited slightly by quercetin. Okadaic acid,
      phenylarsine oxide and sodium pervanadate which inhibit Ser/Thr and Tyr
      phosphatase inhibitors were unable to mimic prolactin action on alpha S1-casein
      gene expression. On the contrary, these inhibitors prevented prolactin action.
      These data suggest that a cascade including protein kinases and phosphatases for
      Ser/Thr and Tyr phosphate is involved in the transduction of the prolactin
      message from its receptor to casein genes. The signal delivered to the mammary
      cells by the extracellular matrix is quite different, possibly involving another
      cascade of protein kinases.

PMID- 7648428
TI  - Ostrich trypsinogen: purification, kinetic properties and characterization of the
      pancreatic enzyme.
AB  - Trypsinogen is a serine protease zymogen (EC.3.4.21.4) which has proved to be of
      key significance in a family of about 20 structurally and functionally related
      pancreatic digestive enzymes. This study was an endeavour to isolate, purify and
      characterize a stable form of ostrich trypsinogen, which has thus far not yet
      been accomplished. Trypsinogen (anionic) was isolated and purified by alkaline
      extraction of pancreatic acetone powder, followed by Toyopearl DEAE 650M,
      hydroxylapatite and LBTI-Sepharose affinity chromatography. The enzyme was
      chemically physically and kinetically characterized, using amidase and esterase
      activity and spectrofluorometric determinations. Effects of CaCl2 and pH, among
      others, were examined. Purification of homogeneous anionic ostrich trypsinogen
      was achieved. Immunochemical analysis and spectrofluorometric reaction with
      sulphonyl-Ala-Ala-Pro-Arg-7-amino-4-methylcoumarin indicated trypsin-free ostrich
      trypsinogen, with an average Mr of 23,016 and a pI of 4.93. N-terminal sequence
      data revealed an unique activation peptide sequence, VPGDADDDK. Certain
      concentrations of Ca2+ enhanced trypsinogen activation, whilst others appeared to
      have the opposite effect. The kcat/Km values obtained at different pHs, using N
      alpha-benzoyl-DL-arginine-p-nitroanilide, p-toluenesulphonyl-arginine-methylester
      and p-toluenesulphonyl-lysine-methylester, followed the pH profile activity trend
      closely, with maximum catalytic activity at about pH 8 for both ostrich and
      bovine activated trypsinogen. Ostrich trypsin has significantly higher amidase
      activity than bovine trypsin, while esterase activities of the two enzymes have
      an inverse ratio. Kinetic pKa values were 7.2 and 7.4 for ostrich and bovine
      activated trypsinogens, respectively. The existence of ostrich trypsinogen in a
      now homogeneous stable form, free of autocatalytic inducing impurities, together
      with its characterization scenario will hopefully make a significant contribution
      to the field of comparative biochemistry. This study also confirms that ostrich
      trypsinogen is closely related to its serine protease counterparts.

PMID- 7648429
TI  - Characterisation of a thermostable pepstatin-insensitive acid proteinase from a
      Bacillus sp.
AB  - An acid proteinase, Wai 21a, produced by a thermophilic Bacillus species (strain
      Wai 21a) has been purified to homogeneity by cation-exchange chromatography,
      phenyl-Sepharose chromatography and anion-exchange chromatography. A pI of 3.8
      was determined by isoelectric focussing. The protein contained some associated
      carbohydrate (20 mol hexose equiv/mol proteinase). Optimal proteolytic activity
      was observed at pH 3.0 (at 60 degrees C). The Leu15-Tyr16 bond was the major site
      of hydrolysis for the oxidized B chain of insulin. Enzyme activity was not
      affected by inhibitors of the cysteine, metallo or serine class of proteinases.
      The aspartate proteinase inhibitor, pepstatin, did not inhibit enzyme activity.
      Inhibition of enzyme activity by 1,2-epoxy-3-(p-nitrophenoxy)-propane indicated
      the presence of at least one carboxyl group essential to the catalytic mechanism
      of the enzyme. Proteinase activity was inhibited by diazoacetyl-DL-norleucine
      methyl ester in a slow and non-specific manner atypical of pepstatin-sensitive
      aspartate proteinases. Wai 21a proteinase may be classified as member of the
      pepstatin-insensitive group of aspartate proteinases. The thermal stability at pH
      3.0 and 60 degrees C increased 2.1-fold (t1/2, 4.5-9.7 hr) in the presence of 5
      mM Ca++. An increase in both pH (3.0-4.5) and Ca++ concentration (0-30 mM)
      resulted in a 15-fold increase (t1/2, 15-230 min) in thermal stability at 75
      degrees C. The amino acid composition of Wai 21a proteinase was found to be
      similar to other pepstatin-insensitive proteinases from bacterial sources and in
      particular similar to the other pepstatin-insensitive proteinases from bacterial
      sources and in particular similar to the thermostable enzyme, kumamolysin.

PMID- 7648430
TI  - 2',5'-oligoadenylate synthetase in interferon-alpha- and acyclovir-treated herpes
      simplex virus-infected cells.
AB  - The 2',5'-oligoadenylate (2-5A) synthetase pathway, induced by interferon-alpha
      (IFN-alpha), has been shown to be responsible for the antiviral action of IFN
      alpha against some viruses. Studies were done to determine the role of this
      pathway in the anti-herpes simplex virus (HSV) action of IFN-alpha alone or in
      combination with acyclovir (ACV), a combination that leads to synergistic anti
      HSV activity. Treatment of human corneal cells or Vero cells with 100 IU/ml of
      IFN-alpha induced expression of 2-5A synthetase mRNA and a 10-fold increase in 2
      5A synthetase production compared with untreated cells. HSV infection alone did
      not induce 2-5A synthetase production, but when IFN-alpha-treated cells were
      infected with HSV, enzyme level was significantly increased (p < 0.05) compared
      with that in IFN-alpha-treated, uninfected cells. HSV infection actually
      decreased the level of 2-5A synthetase mRNA in IFN-alpha-treated cells. Although
      IFN-alpha treatment induced high levels of 2-5A synthetase with or without HSV
      infection, no activation of the latent endonuclease was detected by specific
      cleavage of ribosomal RNA. Treatment of infected cells with 5 microM ACV alone or
      combined with IFN-alpha did not increase 2-5A synthetase or endonuclease
      activities above those detected in cells not treated with ACV. The data indicate
      that the 2-5A synthetase pathway was inducible in corneal cells and Vero cells
      but did not appear to contribute to the anti-HSV activity of IFN-alpha alone or
      the synergistic activity of IFN-alpha combined with ACV.

PMID- 7648431
TI  - Alpha and beta interferons and their receptor and their friends and relations.

PMID- 7648432
TI  - The use of Zwittergent 3-14 in the purification of recombinant human interferon
      beta Ser17 (Betaseron).
AB  - A new method for purifying human interferon-beta SER17 from E. coli-derived
      inclusion bodies has been developed. This procedure eliminates the need for
      strong denaturants, such as sodium dodecyl sulfate or chaotropes. The procedure
      makes use of a nondenaturing detergent and a brief incubation at pH 12 to
      solubilize interferon-beta Ser17 from inclusion bodies. The detergent used was
      Zwittergent 3-14 (nonionic and pH-insensitive), which is included in the class of
      sulfobetaines (RN+ (CH3)2(CH2)xSO3-). Zwittergent 3-14 was used in combination
      with urea to produce a urea/Zwittergent 3-14 washed inclusion body preparation
      enriched in human interferon-beta Ser17 (Betaseron). Solubilization of inclusion
      bodies was accomplished by employing a brief (1 minute) shift to pH 12 in the
      presence of 2.5% Zwittergent 3-14 followed by rapid adjustment to pH 8.0.
      Solubilization was complete, and the solution could be rapidly adjusted to pH 8
      without any observable precipitation of protein. The resultant supernatant could
      be successfully subjected to a number of chromatographic and analytic procedures,
      many of which are not compatible with strong anionic detergents, such as SDS.
      Betaseron was purified from Zwittergent 3-14 solubilized inclusion body lysates
      using both ion-exchange and size-exclusion chromatography. Purified Betaseron
      retained bioactivity and could be refolded by simple dialysis against a
      nonreducing buffer. This method represents a novel procedure for purifying
      Betaseron from inclusion bodies using a nondenaturing detergent and ion-exchange
      chromatography.

PMID- 7648433
TI  - Type I interferon inhibition of superantigen stimulation: implications for
      treatment of superantigen-associated disease.
AB  - The interferons (IFNs) are a family of secretory glycoproteins possessing potent
      antiviral, antiproliferative, antimicrobial, and immunomodulatory activities. It
      has been shown that the IFNs and superantigens have an important effect on the
      course of certain autoimmune disorders, and thus we have examined the effect of
      the type I and type II IFNs on superantigen-induced stimulation. The type I IFNs,
      alpha, beta, and tau, inhibited induction of T cell proliferation by several
      staphylococcal enterotoxin superantigens; the type II IFN, gamma, was without
      effect. The type I IFNs inhibited T cell proliferation to the same extent,
      approximately 50% at 10(3) units of IFN/ml, and in a dose-dependent manner.
      Consistent with inhibition of proliferation, the type I IFNs also inhibited IL-2
      production as well as levels of IL-2 receptor expression. Inhibition was not
      increased by using the IFNs in combination, suggesting that they inhibited
      proliferation by the same mechanism. IFNs alpha and beta, but not IFN-tau, were
      toxic to cells at high concentrations (> or = 10(4) units/ml). Thus, the
      mechanism by which type I IFNs inhibit cell proliferation differs from that
      associated with their toxic effects. A partial reduction of V beta-specific
      superantigen-induced T cell expansion by type I IFNs was also demonstrated using
      flow cytometry. We recently showed that superantigens play an important role in
      the reactivation of experimental allergic encephalomyelitis. The potent
      antiproliferative activities of the type I IFNs strongly suggest the further
      study of their use as therapies for superantigen-associated diseases, such as
      multiple sclerosis and other autoimmune disorders, as well as toxic shock
      syndrome.

PMID- 7648434
TI  - The interferon-induced Mx protein of chickens lacks antiviral activity.
AB  - cDNA sequencing revealed that chick Mx protein consists of 705 amino acids. Its
      84 N-terminal amino acids show no significant sequence homology to other Mx
      proteins. They are followed by 514 residues that include a tripartite GTP binding
      consensus motif. This region shows 50-70% sequence identity to mammalian and duck
      Mx proteins. Sequences near the C terminus, including a leucine zipper motif, are
      also conserved, whereas the intervening 19 amino acids lack sequence similarity.
      This unique sequence corresponds to a highly variable region in mammalian Mx
      proteins, suggesting that it serves as a spacer between functional domains. Chick
      and mouse cells transiently transfected with cDNA expression constructs
      synthesized chick Mx protein at a level that could easily be detected with
      specific antibodies. Chick Mx protein in such cells was mainly cytoplasmic and
      had a granular appearance. Permanently transfected cell lines expressing high
      levels of chick Mx protein could not be established, suggesting low metabolic
      stability of chick Mx protein or incompatibility with cell proliferation. The
      antiviral activity of chick Mx protein was tested at the single-cell level using
      immunofluorescence techniques. Transfected cells expressing chick Mx protein
      showed no enhanced resistance to influenza A virus, vesicular stomatitis virus,
      Thogoto virus, or Sendai virus. Thus, chick Mx joins the list of Mx proteins
      without recognized antiviral activity, supporting the concept that Mx proteins
      serve unrelated functions.

PMID- 7648435
TI  - Synthesis of interleukin-1 receptor antagonist by Thy-1+ and Thy-1- murine lung
      fibroblast subsets.
AB  - IL-1 is a key cytokine that promotes pulmonary inflammation and fibrosis, as a
      result of its ability to stimulate lung fibroblast proliferation and collagen
      synthesis, two hallmarks of fibrosis. The IL-1 receptor antagonist (IL-1Ra) is an
      important natural inhibitor of IL-1-mediated functions. In models of pulmonary
      fibrosis induced by chemotherapeutic agents or noxious particles, administration
      of IL-1Ra significantly ameliorates lung fibrosis. Lung tissue undergoing an
      inflammatory response shows elevations in IL-1Ra, although it is not clear which
      pulmonary cells are responsible for the IL-1Ra synthesis. The purpose of this
      research was to determine whether Thy-1+ and Thy-1- subsets of mouse lung
      fibroblasts were capable of synthesizing IL-1Ra. In this report, it is
      demonstrated for the first time that lung fibroblasts are capable of synthesizing
      IL-1Ra. Both Thy-1+ and Thy-1- parental lines and clones constitutively express
      IL-1Ra mRNA. Quantitation of IL-1Ra protein indicates that Thy-1+ and Thy-1-
      fibroblasts secrete similar levels of secreted but not intracellular IL-1Ra. Thy
      1- fibroblasts accumulate higher levels of IL-1Ra intracellularly. Moreover,
      fibroblast-conditioned supernatants containing IL-1Ra significantly suppress the
      mitogenic response of a T cell clone, D10G4.1, to concanavalin A and IL-1 beta.
      Overall, our observations indicate that Thy-1+ and Thy-1- fibroblasts release IL
      1Ra and possess an IL-1-specific inhibitory activity in their supernatants. In
      vivo, fibroblast-derived IL-1Ra may serve to regulate IL-1-mediated effects in an
      autocrine and/or paracrine fashion to maintain homeostasis in the pulmonary
      interstitium.

PMID- 7648436
TI  - Atypical apoptotic cell death induced in L929 targets by exposure to tumor
      necrosis factor.
AB  - The mechanism by which tumor necrosis factor (TNF) induces cytotoxicity of murine
      fibroblasts was investigated. Electrophoresis of DNA extracted from TNF-treated
      L929 targets showed fragmentation of DNA into a ladder-like pattern, typical of
      cells dying by apoptosis. Morphologic analysis also indicated apoptotic cell
      death, demonstrating clumping and crescentic condensation of chromatin. In
      contrast, chromatin condensation and ladder-like DNA fragmentation were not
      detected in L929 targets dying by necrosis from exposure to heat, repeated cycles
      of freeze-thaw, and sodium azide. Chromatin condensation was an early event,
      detected as early as 6 h of incubation. However, DNA fragmentation (assayed by
      double-stranded fragmentation assay and gel electrophoresis), as well as the
      apoptotic changes detected by Hoechst fluorescence, both occurred later and did
      not precede TNF cytotoxicity (membrane permeabilization detected by trypan blue
      or propidium iodide staining). This atypical pattern of apoptosis was a
      characteristic of L929 target cells rather than a generalized cytotoxic response
      to TNF because TNF-treated squamous cancer cells showed typical features of
      apoptosis (DNA fragmentation before cytotoxicity) and etoposide-treated L929
      cells demonstrated the same atypical kinetics as TNF-treated cells. Zinc
      significantly inhibited TNF cytotoxicity as well as DNA fragmentation of L929.
      However, because DNA fragmentation occurred belatedly in TNF-treated targets,
      lagging behind cytotoxicity, the protection by zinc against TNF appears mediated
      by events that occur before the ultimate endonuclease-induced cleavage of DNA
      into small fragments.

PMID- 7648437
TI  - Heterogeneity of cytokine and growth factor gene expression in human melanoma
      cells with different metastatic potentials.
AB  - The purpose of this study was to determine the mRNA expression level of multiple
      cytokine and growth factor genes in human malignant melanoma. Melanoma cells were
      isolated from several surgical specimens, adapted to growth in culture,
      characterized for their ability to produce experimental metastases in nude mice,
      and assessed for cytokine and growth factor steady-state gene expression. Highly
      metastatic in vivo- and in vitro-derived variants isolated from a single
      melanoma, A375, were also analyzed. Northern blot analyses revealed that all
      melanomas analyzed constitutively expressed steady-state mRNA transcripts for the
      growth and angiogenic factors, basic fibroblast growth factor (bFGF), and
      transforming growth factor alpha (TGF-alpha), which correlated with metastatic
      propensity. Only one highly metastatic melanoma, TXM-1, originally isolated from
      a lymph node metastasis, expressed mRNA transcripts specific for monocyte
      chemotactic and activating factor (MCAF) and granulocyte-macrophage colony
      stimulating factor (GM-CSF). Similarly, of the nine melanomas examined, only TXM
      1 expressed interleukin (IL)-1 alpha, IL-1 beta, and IL-6, important
      immunomodulatory cytokines. These data demonstrate the differential and
      heterogeneous expression of cytokine and growth factor genes in human malignant
      melanoma.

PMID- 7648438
TI  - Monocytes are the major producers of interleukin-1 beta in an ex vivo model of
      local cytokine production.
AB  - Interleukin-1 beta (IL-1 beta) is an early proinflammatory cytokine with multiple
      effects. Several cells are capable of synthesizing this cytokine, but little is
      understood about which cell produces IL-1 in disease states. We examined the
      cellular source of IL-1 in lipopolysaccharide (LPS)-stimulated human whole blood.
      Cytospin preparations of leukocytes were stained for IL-1 beta using a murine
      monoclonal antibody and staining intensity evaluated. In multiple time course
      experiments, LPS-stimulated whole blood showed increases in both plasma and cell
      associated IL-1 beta over 8 h as measured by ELISA (at 4 h, plasma IL-1 beta, 7.2
      +/- 2.7 ng/ml; cell lysates, 1.3 +/- 0.2 ng/ml). Northern blot confirmed the
      upregulation of IL-1 beta mRNA in leukocytes. Immunohistochemistry showed low
      level PMN positivity with no increase in staining intensity over time. In
      contrast, monocytes displayed a marked increase in staining intensity by 4 h,
      correlating with increases in cell-associated and plasma IL-1 levels. Lymphocytes
      remained negative throughout. Our data demonstrate that monocytes represent the
      major source of IL-1 beta in a human ex vivo model that simulates physiologic
      conditions and stimuli.

PMID- 7648439
TI  - Involvement of interleukin-2 in immunologic reconstitution following bone marrow
      transplantation in mice.
AB  - Allogeneic or autologous bone marrow transplantation (BMT) is a curative form of
      treatment for patients with a variety of hematologic disorders. Impaired immune
      reconstitution following BMT may seriously impede successful outcome. In this
      study, the immune function of spleen and thymus was investigated in mice exposed
      to myeloablative total-body irradiation followed by syngeneic BMT. The T cell
      mitogen-induced proliferation of both splenic and thymic cells was delayed.
      Spleen cells started to respond only after 21 days, whereas thymic cells remained
      unresponsive. Kinetic analysis of surface markers revealed the early appearance
      of spleen cells with the CD3+CD4-CD8- phenotype, and the thymus, despite a low
      total number of cells, displayed fast recovery of CD3+CD4+CD8+. At the level of
      mRNA, a mild decrease in interleukin-2 (IL-2) induction following
      phytohemagglutinin activation of spleen cells correlated with a decrease in IL-2
      secretion for only the first 2 weeks following transplantation. The early
      restoration of IL-2 implies other avenues for investigation of the immune
      dysfunction and its correction following syngeneic BMT.

PMID- 7648440
TI  - Direct activation of murine peritoneal macrophages for nitric oxide production
      and tumor cell killing by interferon-gamma.
AB  - Interferon-gamma (IFN-gamma) is known to prime macrophages for tumor cell lysis
      and nitric oxide (NO) production as measured by enhanced sensitivity to
      lipopolysaccharide (LPS). In the present study, the ability of IFN-gamma to
      directly activate peritoneal macrophages from C57BL/6 and Balb/c mice for tumor
      cytotoxicity and NO production was evaluated. Macrophage-mediated tumor cell
      killing was measured by an 18 h 51Cr release assay using P815 mastocytoma cells
      as targets. Concurrent NO production was measured as nitrite in the supernatants
      of macrophage cultures. Incubation of macrophages with IFN-gamma resulted in
      activation of macrophages for tumor cell lysis. IFN-gamma alone also activated
      macrophages for NO production under identical conditions. Addition of LPS along
      with IFN-gamma resulted in synergism in the activation of macrophages for both
      cytolysis and NO production. LPS contamination of the IFN-gamma preparation was
      absent as evidenced by the following criteria: (1) the IFN-gamma preparation as
      well as the reagents used were shown to be free of LPS contamination based on LAL
      endotoxin tests (sensitivity 25 pg/ml), (2) the ability of IFN-gamma to activated
      macrophages was not abrogated by prior treatment of the cytokine with polymyxin
      B, whereas the effect of LPS was inhibited (70-100%) under similar conditions,
      (3) pretreatment of the IFN-gamma preparation with a specific endotoxin
      neutralizing protein did not abrogate the ability of IFN-gamma to induce
      macrophage activation, and (4) heat treatment of solutions containing IFN-gamma
      alone or IFN-gamma+LPS abolished only the effect of IFN-gamma, not that of
      LPS.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7648441
TI  - Detection of rare allelic variants of the interferon-alpha 2 gene in human
      genomic DNA.
AB  - We have analyzed human donor DNA for the presence of sequences corresponding to
      allelic variants of the IFN-alpha 2 locus. Using both restriction enzyme
      digestion of PCR-amplified fragments and sequence analysis of these fragments, we
      have identified the three reported allelic variants, IFN-alpha 2a, IFN-alpha 2b,
      and IFN-alpha 2c, in genomic DNA derived from donors of African or Afro-Caribbean
      origin. This is the first report of the IFN-alpha 2a and IFN-alpha 2c alleles
      occurring in human donor DNA and supports the view that these are variants of the
      predominant IFN-alpha 2b allele rather than arising from mutations occurring in
      cultured cells.

PMID- 7648442
TI  - Pharmacokinetics and biologic activities of human native and asialointerferon
      beta s.
AB  - Glycoproteins are metabolized through an asialoglycoprotein metabolic pathway in
      vivo. They are desialylated and taken up by the liver via an asialoglycoprotein
      receptor. Fibroblast-derived natural human interferon-beta is a glycoprotein
      having a single asparagine-linked sugar chain. Although natural human interferon
      beta may also be metabolized through this pathway, there is very little
      information about the biologic features of human asialointerferon-beta. We
      evaluated the pharmacokinetics and biologic activities of human native and
      asialointerferon-beta s. After intravenous administration to rabbits, human
      asialointerferon-beta was cleared from the blood circulation faster than the
      human native interferon-beta. More asialoprotein was distributed to the liver
      than the native type, but it induced less 2'5'-oligoadenylate synthetase. The
      human asialointerferon-beta had less activity than the human native interferon
      beta on cell growth inhibition and 2'5'-oligoadenylate synthetase induction in
      Hep-G2 and HuH6 human hepatoblastoma cells. Southern blotting using a hepatitis B
      virus-transfected HuH6 cell line, HB611, revealed that the inhibition of
      hepatitis B virus DNA replication by the asialoprotein was weaker than that by
      the native protein. The results showed that the different effects exerted by the
      human native and asialointerferon-beta s may be a result of recognition of the
      sugar chains by rabbit hepatocytes or by human hepatoblastoma cells. The results
      also suggested that the terminal sialic acid of the sugar chains in natural human
      interferon-beta significantly affects its pharmacokinetics and biologic
      activities.

PMID- 7648443
TI  - Purification and N-terminal sequence of a novel interferon-induced 100 kD protein
      secreted by mouse Ehrlich ascites tumor cells.
AB  - Mouse Ehrlich ascites tumor cells secrete a 100 kD protein when they are
      stimulated by murine interferon-beta (2000 IU/ml). This 100 kD protein was
      purified from conditioned medium by chromatography on phenyl-Sepharose CL-4B,
      phosphocellulose, DEAE-Sephacel, and Vydac C4 columns and preparative sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis. A single species of 100 kD
      protein was isolated, and its N-terminal sequence analysis suggested that mouse
      Ehrlich ascites tumor cell-derived interferon-induced 100 kD protein is a novel
      protein.

PMID- 7648445
TI  - Effect of recombinant bovine interleukin-1 beta on viral/bacterial pneumonia in
      cattle.
AB  - Bovine herpesvirus-1 (BHV-1) is an important pathogen of respiratory infections
      in cattle. Its continuing importance lies in its ability to predispose infected
      hosts to bacterial infections (e.g., Pasteurella haemolytica). In this study we
      determined whether the immunoregulatory effects induced by recombinant bovine
      interleukin-1 (rbIL-1) could stimulate appropriate host defense mechanisms to
      influence the course of BHV-1 and P. haemolytica infection in cattle. We first
      evaluated the effect of multiple doses (5 doses of 300 ng/kg) of rbIL-1 in normal
      cattle. An increase in polymorphonuclear (PMN) cells, as well as monocytes, in
      peripheral blood was observed during the course of IL-1 administration. In
      addition, the phagocytic activity of monocytes was increased. Although the
      phagocytic and oxidative burst activities in PMN decreased during the course of
      rbIL-1 treatment, no changes were observed in the bactericidal capacity of these
      cells. Lymphocyte numbers in peripheral blood remained unchanged; however, the
      functional activity of these cells, as measured by IFN-gamma production upon in
      vitro stimulation, was decreased. In the bovine respiratory disease model,
      multiple administration of IL-1 did not influence significantly the progression
      of BHV-1/P. haemolytica infection in cattle. Thus, our results demonstrated that
      IL-1, although not therapeutically effective, could be administered safely as an
      adjuvant, even during the course of BHV-1/P. haemolytica infection.

PMID- 7648444
TI  - Defective expression of interferon-gamma, granulocyte-macrophage colony
      stimulating factor, tumor necrosis factor alpha, and interleukin-6 in activated
      peripheral blood lymphocytes from glioma patients.
AB  - The ability of a mannoprotein antigen from Candida albicans (MP) or interleukin-2
      (IL-2) to induce cytokines in cultures of peripheral blood mononuclear cells
      (PBMC) of glioma patients and healthy controls was evaluated by mRNA expression
      and by protein secretion. The subjects studied were all responsive to both MP and
      IL-2, as assayed by lymphoproliferation of PBMC cultures. In control subjects, MP
      and IL-2 were strong inducers of IFN-gamma, IL-1 beta, TNF-alpha, and GM-CSF mRNA
      expression, but only MP was able to induce considerable levels of IL-6 and IL-2
      mRNA expression. In MP-activated PBMC from glioma subjects, a highly defective
      IFN-gamma, together with a significant reduction in TNF-alpha and GM-CSF mRNA
      expression, was observed. This impairment was paralleled by a decreased
      accumulation of IL-6 and IL-2 mRNA. The pattern of cytokine mRNAs in IL-2
      activated PBMC of glioma patients confirmed the impairment of IFN-gamma mRNA
      expression paralleled by a reduction in IL-6, TNF-alpha and GM-CSF mRNA, compared
      with healthy subjects. Coherently, in PBMC cultures from glioma patients, there
      was a clear-cut decrease in the secretion of IL-6 and TNF-alpha and especially of
      IFN-gamma compared with healthy controls. No or very low levels of IL-4, IL-10,
      and TGF-beta 2 mRNA expression were detected in PBMC cultures of both glioma and
      control populations, irrespective of the activation conditions.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7648446
TI  - Interleukin-4 and interleukin-10 increase endotoxin-stimulated human umbilical
      vein endothelial cell interleukin-8 release.
AB  - The aim of this study was to determine the effect of interleukin-4 (IL-4) and
      interleukin-10 (IL-10) on interleukin-8 (IL-8) release from endothelial cells.
      Confluent monolayers of human umbilical vein endothelial cells (HUVECs) were
      incubated in the absence or presence of 10 ng/ml of bacterial lipopolysaccharide
      (LPS), with 5% human AB serum and recombinant human IL-4 or IL-10 over a dose
      range from 50 fg/ml to 50 ng/ml (final concentration). IL-4 and IL-10 had no
      effect on HUVEC IL-8 release in the absence of LPS. In the presence of LPS, IL-4
      and IL-10 enhanced IL-8 release by approximately 300% compared with LPS
      stimulated cells alone, IL-8 release increasing from 2594 +/- 493 pg/ml (no IL-4
      or IL-10) to 7892 +/- 320 pg/ml (IL-4, 5 pg/ml; p = 0.001) and 8359 +/- 712 pg/ml
      (IL-10, 50 pg/ml; p = 0.002). IL-8 release in response to IL-4 or IL-10 plateaued
      above 5 and 50 pg/ml, respectively. This study suggests that IL-4 and IL-10 may
      be involved in the complex regulation of endothelial cell cytokine production
      during the response to endotoxin.

PMID- 7648447
TI  - Biochemical identity and characterization of the mouse interleukin-2 receptor
      beta and gamma c subunits.
AB  - Although the mouse IL-2 receptor (IL-2R) beta and gamma c subunits have been
      identified by molecular cloning, the biochemical identity of these subunits has
      not yet been established. In the present study, the mouse IL-2R was biochemically
      characterized from cell lines expressing normal and aberrant IL-2R. Using novel
      monoclonal antibodies specific for the beta or gamma c subunits, we established
      that the M(r) of the beta chain is 90,000-100,000 and that of the gamma c subunit
      is 75,000-80,000. Analysis of transfected EL4 cells that expressed alpha, gamma
      c, and truncated beta subunits or mutant EL4 cells, which selectively lacked cell
      surface gamma c, revealed that no other material migrated to a position on SDS
      PAGE characteristic of IL-2/IL-2R beta and IL-2/IL-2R gamma c cross-linked
      complexes, respectively. Thus, the beta and gamma c subunits appear to be the
      sole IL-2R constituents of these IL-2 cross-linked complexes. The IL-2/IL-2R
      gamma c, but not the IL-2/IL-2R beta, complex exhibited enhanced mobility after
      SDS-polyacrylamide gel electrophoresis under nonreducing conditions, suggesting a
      more compact structure for gamma c as a result of intrachain disulfide bonds. The
      primary posttranslational modification of the mouse beta and gamma c subunits is
      N-linked glycosylation. These biochemical studies reconcile past uncertainties
      concerning the subunit composition of the mouse IL-2R and are consistent with a
      model of the IL-2R containing only three subunits.

PMID- 7648448
TI  - Expression of leukemia inhibitory factor and interleukin-11 by human melanoma
      cell lines: LIF, IL-6, and IL-11 are not coregulated.
AB  - Dysregulation in cytokines has been associated with melanomas. For example, loss
      of growth inhibition in advanced melanomas has been associated with interleukin-6
      (IL-6) expression. Because IL-6 belongs to the hematopoietic cytokine family,
      which includes leukemia inhibitory factor (LIF) and interleukin-11 (IL-11), we
      examined the possibility of coordinate expression of LIF, IL-6, and IL-11 in
      three human melanoma cell lines derived from primary lesions (early) and in four
      lines derived from metastatic tumors (advanced). All lines examined produced at
      least low levels of LIF and IL-11 mRNA as measured by semiquantitative reverse
      transcriptase-polymerase chain reaction (RT-PCR). By enzyme-linked immunosorbent
      assay (ELISA), two of three early and three of four advanced lines were found to
      secrete LIF protein. IL-11 was assayed using growth of the responsive B9/11 cell
      line, but only one of seven lines made a low but measurable amount of IL-11.
      Cytokine protein production was not strictly correlated with mRNA abundance, nor
      was it strongly correlated with tumor staging. Recombinant LIF and IL-11 protein
      had no effect on the proliferation of any of the seven lines, suggesting that
      they do not act as autocrine growth factors for these melanomas. Assay of IL-6,
      IL-11, and LIF protein in conditioned medium from early and advanced melanoma
      lines gave no evidence of coordinate expression of these cytokines. We conclude
      that LIF and IL-11 production by melanomas may have some paracrine or endocrine
      function in the course of melanoma progression.

PMID- 7648449
TI  - Rapid and transient phosphorylation of nuclear matrix proteins upon interferon
      alpha treatment in Daudi lymphoma cells.
AB  - Evidence for a rapid and transient hyperphosphorylation of a 45 kD protein in
      isolated nuclei from interferon-alpha-treated Daudi lymphoma cells is presented.
      Extraction of nuclear matrices from these nuclei has provided further evidence
      for the association of such a protein in the nuclear matrix structure. Because
      phosphorylation assays performed directly on nuclear matrices from interferon
      treated cells have revealed rapid and transient increase of gamma 32P-ATP
      incorporation into this 45 kD band, an early involvement of the nuclear matrix in
      the response of the nucleus to the interferon antiproliferative message is
      suggested.

PMID- 7648450
TI  - Comparison of constitutive cytokine release in high and low histologic grade AIDS
      related Kaposi's sarcoma cell strains and in sera from HIV+/KS+ and HIV+/KS-
      patients.
AB  - Kaposi's sarcoma (KS) is both an AIDS-defining disease and the most common HIV
      associated malignancy. A cytokine-mediated pathogenesis for AIDS-KS is implicated
      because AIDS-KS-derived cell strains both respond to and express a variety of
      cytokines. We have reported the establishment of several (n = 18) AIDS-KS cell
      strains and determined that reduced exogenous growth factors are necessary to
      sustain proliferation in isolates from high histologic grade KS lesions. This
      current investigation explored the possibility that there are histologic grade
      associated differences in either the qualitative and/or quantitative constitutive
      release of AIDS-KS growth stimulatory cytokines. Our findings showed that the
      incorporation of HTLV-II cytokine-rich conditioned media induced both qualitative
      and significant quantitative cytokine release, suggesting that exogenous growth
      promoters stimulate constitutive cytokine release. ELISA of our AIDS-KS cell
      strains demonstrated constitutive release of IL-6 (seven of seven), FGF-2 (five
      of seven), GM-CSF (three of seven), and IL-1 beta (one of seven). None of our
      AIDS-KS cell strains constitutively released detectable levels of Onco-M, IL-4,
      PDGF, TNF-alpha, or TNF-beta. In addition, we report that the method of cytokine
      result quantitation significantly affects reported cytokine levels. We determined
      that there was no significant histologic grade-dependent difference in the
      constitutive release of soluble cytokines by in vitro grown cultures of AIDS-KS
      cells. The presence of HIV influenced the sera cytokine profiles by elevating IL
      6 and decreasing PDGF concentrations of HIV+ individuals relative to HIV- healthy
      controls. However, the presence of KS was not associated with unique serum
      cytokine profiles, because no differences were noted in comparisons of HIV+/KS+
      versus HIV+/KS- individuals. Our findings suggest that the local environment is
      key in modulating AIDS-KS cytokine expression and that KS growth-promoting
      factors function at the local or paracrine, not the systemic, level. In
      conclusion, our previous results demonstrated a histologic grade-associated
      difference in the in vitro growth capacity of AIDS-KS cells; with high histologic
      grade isolates displaying a marked growth advantage during culture in minimally
      supplemented media. Findings from this current study reveal that although the
      potential for a constitutive growth loop exists in the high-grade isolates, it is
      not reflected in the free levels of soluble cytokines secreted into the culture
      medium.

PMID- 7648452
TI  - Neurotoxins.

PMID- 7648453
TI  - Psychoimmunology and the practice of allergy.

PMID- 7648451
TI  - Effects of transforming growth factor-beta on bone marrow macrophage Ia
      expression induced by cytokines.
AB  - The initiation of the immune response is regulated, in part, by the effect of
      cytokines on the level of expression of major histocompatibility complex (MHC)
      class II antigens on antigen-presenting cells (APC). The expression of class II
      antigens on B cell and macrophage APC is induced by IFN-gamma and IL-4, and GM
      CSF induces class II expression on macrophages (M phi). Our results show that
      transforming growth factor-beta (TGF-beta) inhibits IL-4- and GM-CSF-induced Ia
      gene expression on bone marrow macrophages but enhances IFN-gamma-induced gene
      expression. Nuclear run-on experiments demonstrated that the inhibitory effects
      of TGF-beta on GM-CSF- and IL-4-induced Ia antigen expression were primarily
      posttranscriptional and augmentation of IFN-gamma by TGF-beta was largely
      transcriptionally regulated.

PMID- 7648454
TI  - Elevated interleukin-4 secretion by T lymphocytes: a feature of atopy or of
      asthma?

PMID- 7648455
TI  - Allergenic crossreactivity of fungi with emphasis on yeasts: strategies for
      further study.

PMID- 7648456
TI  - Peanut allergy.

PMID- 7648457
TI  - Psychiatry in the allergy clinic: the nature and management of patients with non
      allergic symptoms.
AB  - Patients with multiple unexplained somatic symptoms attributed to allergy
      frequently present to physicians and often the physician fails to find evidence
      for allergic or immunological mechanisms underlying the presenting symptoms. This
      article discusses the social and cultural background to this disorder. We then
      consider current explanatory models for symptoms and finally, we consider
      appropriate management, starting with the initial consultation, the
      identification of psychiatric disorders when present, and concluding with
      suggestions for subsequent treatment and guidance on appropriate referral.

PMID- 7648458
TI  - Interleukin-4 and interferon-gamma production in atopic and non-atopic children
      with asthma.
AB  - Previous studies have demonstrated increased production of interleukin-4 (IL-4)
      and reduced production of interferon (IFN)-gamma in stimulated peripheral blood
      mononuclear cell cultures from children and adults with atopic dermatitis,
      however, it is unclear whether such an imbalance of cytokine production relates
      to other childhood atopic diseases such as asthma, and in particular to the
      presence of the atopic state per se. The production of IL-4 and IFN gamma in
      phytohaemagglutin- (PHA)-stimulated peripheral blood mononuclear cell (PBMC)
      cultures from atopic and non-atopic children with moderately severe chronic
      persistent asthma, and a group of age-matched non-atopic controls who did not
      have asthma was examined. Atopic children with asthma produced significantly more
      IL-4 and less IFN gamma than non-atopic children with asthma and non-atopic
      controls who did not have asthma. There was no significant difference in IL-4 or
      IFN gamma production between non-atopic children with asthma and controls. These
      findings demonstrate that an imbalance of IL-4 and IFN gamma production is
      present in atopic asthma as previously documented in atopic dermatitis, therefore
      suggesting that it is a feature of the atopic state per se.

PMID- 7648459
TI  - Detection of IgE antibody against Candida albicans enolase and its
      crossreactivity to Saccharomyces cerevisiae enolase.
AB  - Candida albicans 46 kDa protein, a glycolytic enolase enzyme, is an important
      allergen of the yeast. The purpose of the study was to detect circulating IgE and
      IgG antibodies against C. albicans enolase (CAE). We isolated CAE using
      sequential DEAE Sephacel and P11 column chromatography from spheroplasts of C.
      albicans, and detected IgE and IgG antibody against CAE by immunoblotting.
      Crossreactivity of enolase of C. albicans and Saccharomyces cerevisiae was also
      examined by immunoblotting and immunoblot inhibition test. Among 54 sera with
      positive IgE RAST to C. albicans, IgE antibody against CAE was detected in 20
      sera (37%) and IgG antibody in 27 sera (50%). The allergenic potency of CAE was
      confirmed using a skin-prick test in three patients. Simultaneous IgE binding to
      S. cerevisiae enolase was only observed in four out of 20 sera reacting to CAE.
      Pre-treatment of sera with CAE completely inhibited IgE binding to S. cerevisiae
      enolase. Whereas the latter only partially inhibited IgE binding to CAE. These
      results suggest that CAE shares some crossreacting epitopes with S. cerevisiae
      enolase, representing minor components of CAE but dominant segments of S.
      cerevisiae enolase.

PMID- 7648460
TI  - Localization of major allergens in the dust mite Lepidoglyphus destructor with
      confocal laser scanning microscopy.
AB  - The dust mite Lepidoglyphus destructor is the dominating source of allergens
      giving rise to asthma and rhinitis among farmers. In a previous study of the
      localization of allergens in L. destructor we demonstrated that the 39 kDa
      allergen is associated with digestion. Here we describe the localization of the
      principal 15 kDa allergen and the high molecular weight allergen complex (79 and
      93 kDa) in L. destructor with confocal laser scanning microscopy (CLSM). Cryostat
      cut sections of mite bodies and faecal pellets were probed with mouse monoclonal
      antibodies (MoAbs) raised against the allergens. The 15 kDa allergen disclosed
      labelling of the mite body and most of the faecal pellets but left the
      exoskeleton unlabelled. The binding was widespread, and most intense in the mouth
      region. However, some staining was also observed around the gastrointestinal
      tract. In contrast, the 79 and 93 kDa allergen complex stained the exoskeleton
      and the front part of the mite. Interestingly, we detected no labelling of the
      faecal pellets with the MoAb against the 79/93 kDa allergen. The study indicates
      that the 15 kDa allergen is associated with the digestive tract whereas the
      function of the 79 and 93 kDa allergen complex remains to be elucidated.

PMID- 7648461
TI  - Serum levels of interleukin-4, soluble CD23 and IFN gamma in relation to the
      development of allergic disease during the first 18 months of life.
AB  - Serum levels of Interleukin (IL)-4, Interferon (IFN)-gamma and soluble CD23
      (sCD23) were analysed in a prospective study of 64 infants who were monitored
      from birth to 18 months of age. The findings were related to family history of
      atopy and the development of allergic disease in the infants. Low levels of IL-4
      were detected in 10 of 63 cord blood samples (median 0.14 and range 0.32
      micrograms/l). The levels then increased, both in health and atopic infants,
      reaching a peak at either 6 or 9 months and then decreased up to 18 months of
      age. The children who developed atopic disease during the first 18 months of life
      had significantly higher IL-4 median levels than those who did not, i.e. 0.24
      (range 0.40) vs < 0.10 microgram/l at 3 months, (P < 0.001), 0.40 (range 0.95) vs
      0.13 (0.19) microgram/l at 6 months (P < 0.01), 0.46 (range 0.78) vs 0.10 (0.24)
      microgram/l at 9 months (P < 0.001) and 0.30 (range 1.38) vs 0.10 (0.36)
      microgram/l at 18 months (P < 0.001). The IFN gamma levels were below the
      detection level, i.e. < 100 ng/l in all but 49 of the 196 serum samples that were
      analysed. There was no significant relationship with clinical outcome, nor with S
      IgE levels. Soluble sCD23 levels increased in the infants with age. There was no
      association with either atopic disease, family history of allergic disease or IgE
      antibody levels. In conclusion, IL-4 levels in serum, but not sCD23 and IFN gamma
      are associated with allergic disease in infancy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7648462
TI  - House dust mite allergen levels in dust from schools with smooth and carpeted
      classroom floors.
AB  - A study was conducted to investigate the levels of house dust mite allergen Der p
      I in classroom floor dust from 49 schools with smooth (n = 18) or carpeted (n =
      31) floors. Schools were located in the city of Rotterdam (n = 29) and in a
      number of small communities in the Province of Gelderland (n = 20). Data on
      building characteristics of the schools were obtained. Dust samples were analysed
      for Der p I content, the major allergen of the house dust mite Dermatophagoides
      pteronyssinus. The results showed that in schools with carpeted classroom floors,
      larger amounts of settled dust and higher Der p I levels either expressed as
      concentrations (in ng/g) or loadings (in ng/m2) were found than in schools with
      smooth classroom floors. However, the levels of Der p I were considerably lower
      than in dust collected from floors in homes. Although the Der p I levels were
      low, effects of several building characteristics on the levels were found. Age of
      the floor cover, the number of classrooms in the school and the presence of damp
      spots in the building were related to Der p I concentrations and loadings mainly
      on carpeted floors. Remarkably, schools in the rural area contained significantly
      more dust and Der p I than schools in the urban area. We conclude that dust from
      carpeted classroom floors contains more house dust mite allergen than dust from
      smooth classroom floors, but much less than dust from floors in homes.

PMID- 7648463
TI  - House dust mite fauna in Thailand.
AB  - House dust mites have been shown to be the most important source of allergen in
      Thailand. The results of our initial mite survey were in conflict with previous
      data reported 20 years ago. To evaluate the current condition of mite fauna in
      Thailand, we conducted a larger scale survey of house dust mites in dusts from
      three different parts of the country. A total of 630 mattress dust samples was
      collected from various types of housing from central, northern and northeastern
      parts of Thailand. House dust mites were identified and enumerated by standard
      techniques and 388 dust samples were analysed further for group I antigen by a
      two-site monoclonal antibody enzyme-linked immunosorbent assay. House dust mites
      were identified in 555/630 (88.1%) of dust samples collected; 27.6% of these 555
      samples contained over 100 mites per gram of fine dust. Dermatophagoides
      pteronyssinus was the most abundant species found with a mean count of 87.2 mites
      per gram of dust (range 1-1460). Group I antigen was detected in 380/388 (97.9%)
      samples analysed and 330 of which (86.8%) contained over 2 micrograms/gm of group
      I antigen. The highest density of mites was found in dusts from northern Thailand
      whereas dusts with highest amount of antigen were those collected from the
      northeastern part. Some degree of correlation between mite count and mite
      allergen was observed (r2 = 0.133, P < 0.001). No significant difference in the
      mite count and mite allergen was found among various types of housings. House
      dust mites are the source of allergens ubiquitously found all over
      Thailand.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7648464
TI  - Prevention of asthma with ketotifen in preasthmatic children: a three-year follow
      up study.
AB  - Growing morbidity and mortality rates call for research towards more effective
      methods of preventing asthma. During the last decade several groups have reported
      the results of natural history and asthma prevention studies. However, the
      attempt to prevent development of asthma in genetically predisposed children, has
      not resulted in a generally accepted management scheme. The aim of this study was
      to evaluate the effectiveness of ketotifen in preventing the onset of asthma in
      infants considered to be at high risk of developing the disease, but who had no
      history of respiratory obstruction. These children have been described as
      preasthmatic. In this double-blind, placebo-controlled, parallel study, 100
      infants with a family history of major allergy and elevated serum IgE levels, but
      with no history of bronchial obstruction, were treated with either ketotifen (n =
      50) or placebo (n = 50) over a 3-year period. There were no statistically
      significant differences between the two groups with regard to age, sex, degree of
      hereditary allergy, levels of serum IgE upon joining the study, and family
      smoking habits. At the end of 3 years, only four of the 45 infants who had
      received ketotifen had developed asthma (9%). Of the 40 children given placebo,
      14 had developed asthma (35%) (P = 0.003). These results suggest that ketotifen
      is effective in preventing the onset of asthma in preasthmatic children.

PMID- 7648465
TI  - Castration of pets does not prevent allergy to pets.

PMID- 7648466
TI  - Flexible docking of peptides to class I major-histocompatibility-complex
      receptors.
AB  - We present a new method for docking flexible peptides to class I Major
      Histocompatibility-Complex (MHC) receptors. Docking is performed in two steps:
      (a) The charged terminal peptide residues are located by randomly distributing
      multiple copies of each in volumes of approximately 150 A at either end of the
      binding groove, and then minimizing the system energy using a modified multiple
      copy search algorithm. This is followed by (b) construction of the intervening
      chain using the multiple-copy bond-scaling-relaxation loop closure algorithm. In
      both steps, the copies tend to cluster and the size of the resulting clusters is
      proportional to the basin of attraction of the corresponding energy well. We show
      that native MHC-bound peptides have broad minima and, consequently, that
      misfolded, low-energy peptide conformations can be eliminated by restricting
      consideration to groups of peptides which cluster into broad minima. The accuracy
      of the method is assessed by comparing the predictions with crystallographic data
      for three different MHC peptide systems, at various degrees of stringency: (a)
      the extent to which we can determine side chain function (anchor vs. T-cell
      epitopes); (b) the extent to which we can determine the peptide-receptor
      orientation; and (c) the accuracy with which we can predict atomic coordinates.
      We find the method correct on (a) for 19 of the 22 non-Gly positions; the
      failures appearing to be a consequence of omitting solvation. Predictions related
      to (b) are also very encouraging, with the overall orientation of the predicted
      peptides being very similar to the crystal conformation, when measured by the
      hydrogen bonding pattern between the two. The degree of success in predicting
      atomic coordinates varied considerably, however, from 1.4 A for the HLA-A2
      peptide to 2.7 A for the Kb peptide. The inaccuracy of the latter appears to
      reflect an incomplete target function, most likely the ommission of solvation.
      The calculations thus define the current limits of accuracy in docking flexible
      peptides to Class I receptors and identify the methodological improvements that
      must be made for the next advance in accuracy.

PMID- 7648467
TI  - An arrayed library enriched in hncDNA corresponding to transcribed sequences of
      human chromosome 19: preparation and analysis.
AB  - A simple technique for preparation of libraries of the human chromosome specific
      transcribed sequences is developed. It uses hnRNA from human-rodent hybrid cell
      lines containing particular human chromosomes or their fragments and includes
      three stages: (i) reverse transcription of the hnRNA with Alu-specific primers
      directing the transcription beyond the Alu-repeats to flanking non-repetitive
      sequences of the chromosome; (ii) nested primer PCR strategy with specifically
      designed primers; (iii) direct selective cloning of the second-stage nested
      primer PCR products. An arrayed hncDNA library was prepared from a hybrid cell
      line containing chromosome 19 and fragments of 22 and X chromosomes. The library
      contains around 98% of human-specific transcribed sequences. Sequences of 52
      human-specific, according to PCR analysis, clones differed from each other and
      had no close analogs in the EMBL Data Bank. Of 17 clones assigned to certain
      human chromosomes, 9 belonged to chromosome 19, 5 to chromosome 22 and 3 to
      chromosome X. Some of the human specific clones contained repetitive elements
      scattered over different human chromosomes. Clones from hncDNA libraries are
      useful as STSs/ESTs, as probes for detecting full-size genes in genomic
      libraries, for RFLP analysis and for identification of chromosome specific cDNAs.

PMID- 7648468
TI  - The development of single molecule environmental sensors.
AB  - The participants at the meeting reflected the broad range of expertise that is
      required to realize improved methods for extremely high sensitivity or single
      molecule detection. It is quite clear that the answers lie at the interface of
      biology, chemistry, engineering and molecular design.

PMID- 7648469
TI  - A system for assessment of monokine gene expression using human whole blood.
AB  - Monocyte derived cytokines (monokines) are important mediators in inflammatory
      diseases and cancer. Control of monokine expression is also a major therapeutic
      target in autoimmune inflammation. Whole blood cultures permit examination of
      monokine expression under conditions which emulate the in-vivo environment whilst
      avoiding many of the artefacts associated with monocyte separation and culture.
      Here we describe a system for measuring interleukin-1 beta, interleukin-1 alpha,
      interleukin-6 and tumour necrosis factor-alpha mRNA in stimulated human whole
      blood ex-vivo, which can be applied to specimens from treated patients.
      Oligodeoxyribonucleotide probes are designed to allow standardisation of
      hybridisation and washing procedures. Washing and reprobing of membranes in
      appropriate sequence permits measurement of each monokine mRNA and mRNA for
      glyceraldehyde-3-phosphate dehydrogenase in only 7 ml of lipopolysaccharide
      stimulated human blood. The method has been used successfully in studies of
      dexamethasone and methotrexate action on lipopolysaccharide stimulated IL-beta
      gene expression.

PMID- 7648470
TI  - DNA fingerprinting of Musa cultivars with oligodeoxyribonucleotide probes
      specific for simple repeat motifs.
AB  - Using synthetic oligodeoxyribonucleotide probes against restriction-digested
      genomic DNA, we have established DNA fingerprinting of Musa cultivars. Of all the
      enzymes used, Eco RI and Hin dIII were found to be most informative, giving rise
      to individual specific band patterns with oligonucleotide probes of 15- to 18
      base residues. Of the several probes and enzyme combinations used, the 15mer GACA
      probe with Eco RI and Hin dIII digests revealed a maximal level of polymorphism,
      and the probability of obtaining an identical band pattern between any two random
      genotypes was calculated to be 1.50 x 10(-9) and 1.59 x 10(-9), respectively.
      Oligonucleotide probes longer than 22 residues were also used but did not
      hybridize. The present approach is useful for cultivar identification and for
      overall genome analysis to establish relatedness among the various accessions of
      the Musa germplasm originating from different geographic locations. The relevance
      of using synthetic oligonucleotide probes based on simple repeat motifs for
      achieving DNA fingerprinting pattern is discussed.

PMID- 7648471
TI  - Generation of polymerase chain reaction-specific probes for library screening
      using single degenerate primers.
AB  - Degenerate oligonucleotide primers were made to peptide sequences from
      hydroxylamine oxidoreductase (HAO) from Nitrosomonas europaea. The primers were
      used singly in PCR reactions to amplify portions of the gene for HAO from genomic
      DNA. Southern hybridizations using fragments amplified with each primer showed
      that they labeled the same genomic DNA fragments. The PCR-amplified fragments
      were successfully used to screen a gene library for clones containing the HAO
      gene. The method of isolating genes by PCR with single primers has general
      utility.

PMID- 7648472
TI  - Assessment of amplicons in the DNA from boiled tissue by PCR and AP-PCR
      amplification.
AB  - Polymerase chain reaction (PCR) is a technique sensitive enough to amplify small
      DNA fragments a billion-fold. The generation of amplicons either by PCR with a
      set of oligo primers or by arbitrarily primed AP-PCR with a single
      oligonucleotide primer is based on the availability of intact template and
      priming sites. With these approaches, it is possible to generate specific and
      random amplicons to assess the extent of damage to DNA caused by any of the
      physical, chemical, or environmental factors. We report the amplification of sex
      chromosome and autosome specific loci in the buffalo (Bubalus bubalis) genome by
      symmetrical and AP-PCR performed on DNA samples isolated from the muscle tissues
      that were boiled (treated) for different lengths of time. No difference was
      noticed in the amplification profile of DNA cooked for various lengths of time.
      However, after HinfI treatment, AP-PCR amplification of these DNAs revealed more
      bands on agarose gel than unrestricted samples. The successful amplification of
      the DNA samples isolated from the boiled tissues is attributed to the intactness
      of the amplicons. This suggests that despite storage for more than a year and
      subsequent heat treatment to the muscle tissues, the DNA remains a good substrate
      for PCR and AP-PCR amplification. Relevance of this work in the context of DNA
      probe technology is discussed.

PMID- 7648473
TI  - Predigestion of DNA template improves the level of polymorphism of random
      amplified polymorphic DNAs in wheat.
AB  - Random amplified polymorphic DNA (RAPD) analysis in wheat has proven to be poor
      in its levels of both reproducibility and polymorphism. By digesting the
      template, prior to performing PCR, with frequently cutting restriction enzymes,
      the level of polymorphism was improved. RAPD profiles from certain primers were
      not affected by this pretreatment of the template, but other primers produced
      distinct profiles from each of several restriction enzymes assayed. Some
      polymorphisms were specific to one or more restriction digests, but none involved
      the simple loss of bands from the unrestricted template profile. Genotypic
      comparisons enabled the selection of primer-restriction enzyme combinations that
      enabled polymorphic and mappable patterns to be produced both between wheat
      varieties and between wheats with and without chromosomal segments deriving from
      related species.

PMID- 7648474
TI  - [XX National Congress of the Spanish Association for the Study of the Liver.
      Madrid, 19-20 May 1995. Abstracts].

PMID- 7648475
TI  - Proposed budget sets healthcare changes.

PMID- 7648476
TI  - Why are the principles of physics and anatomy important in treating osteoporosis?

PMID- 7648477
TI  - Vitamin D supplementation in the elderly: review of safety and effectiveness of
      different regimes.
AB  - Vitamin D deficiency is common in the elderly, especially in countries where
      effective sunlight or exposure to sunlight is limited. Two regimes for vitamin D
      supplementation--low-dose daily oral administration and intermittent high-dose
      administration--were examined with regard to safety and effectiveness. Eleven
      papers reporting studies in 449 elderly subjects were reviewed. On low-dose
      continuous supplementation mean concentration of 25 hydroxyvitamin D (25(OH)D)
      ranged from 57 to 105 nmol/L compared to 55 to 87 nmol/L following high-dose
      supplementation. These mean values fall within the physiological range for young
      adults. Hypercalcemia occurred in only 3 subjects and was associated with a
      predisposing cause in 2 of 3 subjects. We suggest that low dose continuous
      supplementation (10 to 20 micrograms daily) is the regime of choice but high-dose
      intermittent supplementation (2.5 mg six monthly) may be suitable where
      compliance is poor.

PMID- 7648478
TI  - A longitudinal assessment of bone loss in women with levothyroxine-suppressed
      benign thyroid disease and thyroid cancer.
AB  - To determine if differing degrees of levothyroxine (LT4) suppression therapy for
      benign and malignant thyroid disease are associated with proportionately
      increased rates of bone loss, this longitudinal assessment of bone densitometry
      changes (single-photon and dual-photon absorptiometry) was conducted in three
      groups of subjects: 24 thyroid cancer patients who were treated with near-total
      thyroidectomy, radioiodine ablation, and aggressive LT4-suppression; 44 patients
      who were treated with more conservative LT4-suppression for benign thyroid
      disorders; and 24 normal controls. Bone densitometry values were adjusted for
      age, weight, height, and menopausal status. The rates of bone loss in benign LT4
      suppressed patients were greater than those in controls at the midradius, distal
      radius, lumbar spine, and femoral neck. The rates of loss in the thyroid cancer
      patients were also greater than those in the controls at all four sites and
      greater than in the benign LT4-suppressed patients at the midradius, distal
      radius, and femoral neck but not in the lumbar spine. Rates of bone loss were not
      significantly correlated with LT4 dose or with the serum level of T4 or TSH. LT4
      suppression therapy for benign thyroid disease is associated with accelerated
      bone loss. More aggressive LT4-suppression for thyroid cancer is associated with
      even greater bone loss, particularly in cortical bone regions. These risks must
      be weighed against the benefits of LT4 therapy in individual patients.

PMID- 7648479
TI  - Quantitative ultrasound assessment of bone in patients with primary
      hyperparathyroidism.
AB  - Quantitative ultrasound measurements were done in a group of 26 patients (4 males
      and 22 females, aged 55.4 +/- 14.2 years) with primary hyperparathyroidism, and
      the results were compared with bone mineral density (BMD) carried out at various
      skeletal sites. Speed of sound (SOS), broadband ultrasound attenuation (BUA), and
      stiffness were measured with the Achilles ultrasound bone densitometer (Lunar
      Corp., Madison, WI). Mean +/- SD values of SOS, BUA, and stiffness in patients
      with primary hyperparathyroidism were 1522 +/- 38 m/seconds, 111 +/- 16 dB/MHz,
      and 80.4 +/- 19.8%, respectively. There were significant differences of mean T
      score BUA values (-0.63 +/- 1.11) compared with corresponding T-score BMD values
      found at ultradistal (-1.85 +/- 1.73, P < 0.01), proximal radius (-2.40 +/- 2.13,
      P < 0.001), and total femoral (-1.60 +/- 1.32, P < 0.001) sites. Correlation
      coefficients between both SOS and BUA values with BMD measurements at specific
      skeletal sites varied, but stiffness correlated moderately (0.6-0.9) with BMD.
      Our data strongly indicate that in patients with primary hyperparathyroidism,
      bone structure of some skeletal sites, as evaluated by BUA measurement, is
      compromised to a lesser extent than BMD. In this respect it is interesting to
      note the lack of significant differences (in terms of mean T-score values) in the
      comparison of two sites of mostly trabecular composition, that is, the lumbar
      level (-1.17 +/- 1.54) and the femoral Ward's triangle (-0.99 +/- 1.25). Our
      results seem to lend further support to the hypothesis that in primary
      hyperparathyroidism cancellous bone architecture might be preferentially
      maintained.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7648480
TI  - Phosphorus-31 in vivo magnetic resonance spectroscopy of bone fails to diagnose
      osteoporosis.
AB  - The values of in vivo T1 relaxation time (T1) of phosphorus atoms of wrist bone
      have been measured by phosphorus-31 magnetic resonance spectroscopy (MRS) in 65
      menopausal women separated into three groups: (1) age-matched women without any
      paraclinical or clinical osteoporosis; (2) patients with paraclinical
      osteoporosis detected only by dual photonic absorptiometry; and (3) women with
      clinical osteoporosis with vertebral fractures. No significant differences were
      found in T1 values in the presence of paraclinical or clinical osteoporosis as
      compared to control values. No relationships were found among the T1, the value
      of the Z-score, the value of bone mineral content, the age of patients, the
      number of their children, and the age of menopause. Phosphorus-31 magnetic
      resonance spectroscopy of the wrist fails to separate osteoporotic from
      nonosteoporotic women and cannot be clinically used at this time to perform a
      noninvasive diagnosis of osteoporosis.

PMID- 7648481
TI  - Calcium tracer kinetics show decreased irreversible flow to bone in
      glucocorticoid treated patients.
AB  - Osteopenia resulting from pharmacologic doses of glucocorticoids is well known.
      Previously, there has been no satisfactory quantitative model describing the
      kinetics of calcium flow in subjects on chronic steroid use. A mathematical model
      of calcium isotope interaction with bone is described and applied to determine an
      estimate of kinetic parameters characterizing these changes. Calcium tracer
      dilution kinetics after a bolus injection of 42Ca were measured in 14 subjects
      with juvenile dermatomyositis, 6 on prednisone regimens and 8 on treatment
      regimens without prednisone. Irreversible tracer loss from plasma bone is found
      to be significantly reduced (P = 0.043) in the glucocorticoid-treated patients
      compared with patients on nonsteroid regimens. Reversible flow to bone is noted
      to be similar in the two groups. These results suggest a direct effect of
      glucocorticoids on osteoblast function.

PMID- 7648482
TI  - Incidence of proximal femur fracture in an urbanized community in Saudi Arabia.
AB  - Osteoporosis, an age-related disorder, is a major contributor to bone fractures
      among the elderly, especially postmenopausal women. Variable incidence have been
      reported from different geographical areas, however, none as yet from Saudi
      Arabia. We have reviewed case records of Saudi residents of Riyadh city, who were
      40 years or older and who were admitted to any of the local acute-care hospitals
      over a period of 12 months (July 1990-June 1991) with a diagnosis of proximal
      femur fracture (PFF). Of these, 103 were diagnosed with PFF; 52 (50%) were male
      and 51 (50%) were female. Eighty-eight (85%) patients reported mild trauma as the
      precipitating cause for their fracture (41 males and 47 females). The median and
      mean (SD) age of all patients were 75 and 73 (14) years, respectively, with no
      significant difference between male and female patients. The incidence per
      100,000 of PFF for males in age groups 40-49, 50-59, 60-69, and over 70 years was
      7, 22, 36, and 251, respectively; the incidence per 100,000 for females in the
      same age groups was 4.5, 14.6, 7.9, and 394, respectively. The female:male ratios
      for the same age groups were 0.6, 0.7, 2.2, and 1.6. The incidence of PFF for
      male and female patients over the age of 50 years was 71 and 100, respectively,
      with a female:male ratio of 1:4. The anticipated incidence of osteoporotic
      fracture in Saudi Arabia is expected to be higher than the present one with the
      population's anticipated increase in life expectancy.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7648483
TI  - Prevention of postmenopausal bone loss by rectal calcitonin.
AB  - A group (150) of healthy women, who had been menopausal for less than 5 years and
      who had never received any form of treatment to prevent bone loss were entered
      into a randomized, controlled study comprising three arms. They were randomly
      allocated to the double-blind administration of five suppositories per week
      containing either 100 IU of salmon calcitonin or a placebo, or to a group
      receiving a suppository containing 200 IU of salmon calcitonin three times per
      week. All women received 500 mg/day of calcium supplementation. After 12 months,
      bone mineral density (BMD) of the spine, measured by dual energy X-ray
      absorptiometry, decreased significantly (P < 0.01) in the placebo group by 3.1%
      (SD: 3.6%) but did not change in the two calcitonin groups [+1.3% (3.5%) with 100
      IU/day and +2.3% (4.0%) with 200 IU 3/week]. The differences in response between
      the placebo group and the two calcitonin groups were significant (P < 0.05), but
      the difference between the two regimens of calcitonin administration was not. No
      differences appeared among the three groups for the response at the level of the
      hip. Evolution of biochemical markers reflecting bone turnover did not differ
      significantly among groups. Nearly 40% of the women withdrew prematurely because
      of local (rectal or intestinal) intolerance to repetitive suppositories, with a
      nonsignificantly different frequency in the placebo or calcitonin groups. We
      conclude that rectal calcitonin might be an interesting preventive approach
      against trabecular postmenopausal bone loss but that long-term acceptability of
      suppositories should be evaluated in view of each patient's sensibility or
      cultural background.

PMID- 7648484
TI  - An EPR study of intact and powdered human tooth enamel dried at 400 degrees C.
AB  - An EPR study of human tooth enamel dried at 400 degrees C is presented. Enamel
      blocks as well as powdered samples were investigated. The discussion deals mainly
      with three different spectral components, i.e., a CO3(3-) and two different CO2-
      signals. Using the anisotropic enamel block spectra, a convincing differentiation
      between the latter two radicals was possible. The first CO2- signal shows no
      dependence on the orientation of the enamel blocks, disappears from the spectrum
      upon heating, and was assigned to a surface radical. The second CO2- component is
      mainly responsible for the angular variation of the enamel blocks and is assigned
      to a bulk position. For the CO3(3-) ion, the (pseudo) angular variation of its
      isolated spectrum is presented and discussed. By means of the results presented
      in this study, earlier interpretation problems are considerably reduced.

PMID- 7648485
TI  - Recombinant bone morphogenetic protein-2 enhances bone healing, guided by
      osteopromotive e-PTFE membranes: an experimental study in rats.
AB  - It has been shown earlier that it is possible to improve bone healing, to
      regenerate previously existing bone, and to create new bone by means of an
      osteopromotive membrane technique. The present study addresses the question of
      whether it is possible to combine this technique with a locally applied factor,
      stimulatory to osteogenesis. Circular transosseous 'critical size' defects in
      mandibles of rats were either implanted with recombinant human bone morphogenetic
      protein type 2 (rhBMP-2) or were left empty; half the number of implanted and
      half the number of empty defects were covered with an expanded
      polytetrafluoroethylene (e-PTFE) membrane (GORE-TEX). Results were evaluated
      after 12 and 24 days of healing by a histomorphological scoring system.
      Implantation of rhBMP-2 alone resulted in bony bridging of the defect after only
      12 days, but also in voluminous amounts of new bone outside the original defect
      area. When rhBMP-2 was combined with membrane, newly formed woven bone bridged
      the defect and the bone contour was maintained by the membrane. The combined
      treatment with membrane and rhBMP-2 demonstrated a significantly better bone
      healing than with e-PTFE membrane alone at both 12 days and 24 days of healing.
      It was concluded that rhBMP-2 has a strong osteoinductive potential and, in
      contrast to what was found earlier with other types of BMP preparations, this
      potential was retained when combining the rhBMP-2 with the osteopromotive
      membrane technique, yielding better bone healing than with the membrane alone,
      and at the same time maintaining the bone contour.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7648486
TI  - The rate of osteoclastic destruction of calcified tissues is inversely
      proportional to mineral density.
AB  - This study examined the relative ease with which three dissimilar mineralized
      tissues from one individual organ were resorbed by osteoclasts in vitro. Cells
      released from the long bones of prehatch chicks by agitating fragments of the
      chopped bones in medium were cultured for 24 hours on slices cut from an Elephas
      maximus molar so that enamel, dentine, and coronal cementum were present in bands
      on the surface of the slice. The resultant pits were measured using a video-rate,
      line-confocal reflection light microscope system. Variations in tissue
      mineralization were characterized by analysis of digital backscattered electron
      images. The enamel pits were smaller than the dentine and the cementum pits, but
      the dentine and cementum pits were not significantly different from each other.
      The sizes of the pits correlated with the relative mineral densities of the three
      tissues, showing that the rate of osteoclastic destruction of calcified tissues
      is inversely proportional to mineral density. This indicates that the initial
      step in osteoclasis, the removal of the mineral phase, determines the volume
      removed and is the rate-limiting step.

PMID- 7648487
TI  - Conformational changes of bovine bone osteonectin induced by interaction with
      calcium.
AB  - To clarify calcium-induced conformational changes in bovine bone osteonectin, the
      protein was labeled with fluorescein isothiocyanate (FITC) in the presence and
      absence of calcium. By calcium titration using fluorescence spectrometry, it was
      demonstrated that FITC-osteonectin labeled in the presence of 2 mM CaCl2 showed a
      much higher affinity for calcium ions than did that labeled in the absence of
      calcium ions. The midpoint for completion of the increase in the intrinsic
      fluorescence (K0.5) of the two were 1 x 10(-7) M and 5 x 10(-7) M, respectively.
      By tryptic digestion and isolation of the fluorescent peptide of both FITC
      osteonectins, the site of FITC-labeling was determined to be Lys174. Furthermore,
      it was found that the efficacy of labeling in this specific binding site was
      three times higher in the FITC-osteonectin labeled in the presence of 2 mM CaCl2
      than in that labeled in the absence of calcium. The results indicate that in the
      presence of 2 mM CaCl2 the microenvironment around Lys174 of osteonectin was more
      open to modification than in the absence of calcium.

PMID- 7648488
TI  - An ultrastructural evaluation of the effects of cysteine-proteinase inhibitors on
      osteoclastic resorptive functions.
AB  - This study was designed to evaluate the effects of specific and potent cathepsin
      inhibitors on osteoclastic resorptive functions in vitro by means of a novel
      ultrastructural assay system. Mouse bone marrow cell-derived osteoclasts were
      suspended on dentine slices and cultured for 48 hours in the presence of either E
      64 (a generalized cysteine proteinase inhibitor) or Z-Phe-Phe-CHN2 (a selective
      cathepsin L inhibitor). After the removal of cultured osteoclasts, co-cultured
      dentine slices were examined using electron microscopy: backscattered (BSEM),
      scanning (SEM), and atomic force (AFM). In morphometric analyses of BSEM images,
      there were no significant differences in the areas of demineralized dentine
      surfaces between control and inhibitor-treated groups, suggesting that cathepsin
      inhibitors had no effect on dentine demineralization by cultured osteoclasts.
      However, in SEM and AFM observations, both inhibitors remarkably reduced to the
      same extent, the formation of deep resorption lacunae on dentine slices that had
      resulted from degradation of matrix collagen. In addition, Z-Phe-Phe-CHN2
      treatment produced deeper, ring-like grooves with little collagen exposure in
      shallow resorption lacunae. These results strongly suggest that (1) cathepsins
      released by osteoclasts are involved in the formation of deep resorption lacunae,
      and (2) cathepsin L plays a key role in bone resorption.

PMID- 7648489
TI  - Dexamethasone enhances the effects of parathyroid hormone on human periodontal
      ligament cells in vitro.
AB  - Periodontal ligament cells (PDL) are thought to play a major role in promoting
      periodontal regeneration. Recent studies, focused on characterizing PDL cells,
      have been directed at establishing their osteoblast-like properties and
      determining biological mediators and/or factors that induce osteoblastic cell
      populations in the PDL. The glucocorticoid, dexamethasone (Dex), has been shown
      to selectively stimulate osteoprogenitor cell proliferation and to induce
      osteoblastic cell differentiation in many cell systems. In the present study the
      ability of Dex to modulate parathyroid hormone (PTH)-stimulated cAMP synthesis in
      cultured human PDL cells was examined. PDL cells, obtained from premolar teeth
      extracted for orthodontic reasons, were cultured with Dex (0-1000 nM) for 7 days
      prior to PTH (1-34) stimulation. The exposure of PDL cells to Dex resulted in a
      dose-dependent increase in cAMP production in response to PTH stimulation. This
      response was seen in cells obtained from three different patients. The first
      significant Dex effect was seen on day 7 when compared to day 1 for 100 nM Dex.
      PTH (1-34) stimulation caused a dose-dependent increase in cAMP synthesis after
      Dex (1000 nM) treatment for 7 days. Conversely, stimulation of the cells with PTH
      (7-34) (0-1000 nM) did not increase cAMP production in PDL cells after Dex
      treatment. Forskolin- (1 microM) and isoproterenol- (1 microM) stimulated cAMP
      synthesis was not augmented by Dex treatment. Dex treatment did not alter
      calcitonin-(1 microM) stimulated cAMP production in PDL cells. Glucocorticoid
      enhancement of PTH-stimulated cAMP synthesis in these cells supports the presence
      of an osteoblast-like population in the PDL, in vitro.

PMID- 7648490
TI  - Purification and immunochemistry of a soluble matrix protein of the chicken
      eggshell (ovocleidin 17).
AB  - The protein components of biomineralized structures (matrix proteins) are
      believed to modulate crystal nucleation and growth, and thereby influence the
      shape and strength of the final structure. The chicken eggshell contains a
      complex array of distinct matrix proteins. The most abundant of these was
      purified to homogeneity by a combination of anionic exchange and hydroxyapatite
      chromatographies. Antibodies to this protein were raised in rabbit, and utilized
      for Western blotting and immunohistochemistry. These studies indicated that the
      17 kDa antigen (ovocleidin 17, OC-17) is found in the shell gland mucosa, and
      that only the tubular gland cells were positive. Immunohistochemistry with
      decalcified shell indicated that OC-17 is uniformly distributed throughout the
      shell matrix, but concentrated in the mammillary bodies. Our results indicate
      that this protein is secreted during shell formation and becomes incorporated
      into this structure. It may therefore play a role in the crystallization process
      and influence the properties of the resulting eggshell.

PMID- 7648492
TI  - Fixed ratio between radial cortical volume and density measured by peripheral
      quantitative computed tomography (pQCT) regardless of age and sex.

PMID- 7648491
TI  - Ototoxicity associated with intravenous bisphosphonate administration.
AB  - The development of ototoxicity in association with intravenous pamidronate
      treatment of Paget's disease is described. The patient developed hearing loss,
      vertigo, and tinnitus which were exacerbated by subsequent infusions. This
      potentially serious drug side-effect does not appear to have been reported
      previously in patients with Paget's disease.

PMID- 7648494
TI  - [Effect of glucocorticoid receptor blockade on pulmonary and renal vascular
      permeability in scalded rats].
AB  - With glucocorticoid receptor (GR) blockade by RU38486, a competitive antagonist
      of GR, the change in contents of FITC labeled albumin (FITC-albumin) in pulmonary
      and renal tissue in scalded rats have been measured to study the changes in
      vascular permeability. The result showed that the contents of FITC-albumin in
      pulmonary and renal tissue in the scalded rats were markedly higher than those of
      the controls (lung: P < 0.05, kidney: P < 0.001). When the scalded rats were
      given GR blockade, the contents of FITC-albumin in pulmonary and renal tissue
      were significantly higher than those of rats with scald only (P < 0.05). The
      results indicated: (1) the pulmonary and renal vascular permeability in scalded
      rats was markedly enhanced; (2) GR blockade might aggravate the increase in
      vascular permeability caused by scald, so that the protective effect of
      glucocorticoid (GC) on vascular permeability seemed to be reversed.

PMID- 7648493
TI  - Comments on "cyclosporin does not affect the absolute rate of cortical bone
      resorption at the organ level in the growing rat".

PMID- 7648495
TI  - [Multiple organ injury after delayed fluid resuscitation in severely scalded
      rats: role of oxygen free radicals].
AB  - Sixty gnotobiotic rats with 5 strains of bacteria in intestine were randomized to
      4 groups: (1) Sham injury group (controls, n = 6). (2) Early fluid resuscitation
      (EFR) group (n = 24), receiving fluid resuscitation (Parkland formula)
      immediately after scald (40% TBSA, third degree). (3) Delayed fluid resuscitation
      (DFR) group (n = 24) receiving resuscitation 6 hours later after scald. (4)
      Treatment group (n = 12) receiving DFR and the therapy of VitC and VitE. At 8,
      24, 48 and 72 hours after injury, the animals (n = 6, at each point) were
      sacrificed and the content of oxygen free radicals (OFR), SOD,GSHPx and MDA in
      the heart, liver, kidney and lung were determined. Morphological Changes of
      organs, PaO2, PaCO2 and the content of serum CPK, LDH, GPT, GOT, BUN and Cr were
      also examined. Both EFR and DFR groups demonstrated elevated content of OFR and
      MDA and reduced content of SOD and GSHPx in their organs. Morphological and
      serological changes were also observed. All these changes were more obvious in
      DFR group than in EFR group. After the treatment of VitC and VitE, the changes
      were ameliorated. Our results suggested that DFR induced the production of OFR,
      resulting in lipid peroxidation and that OFR injury might be one of the main
      factors in the pathogenesis of multiple organ injury after DFR.

PMID- 7648496
TI  - [The injury of heart of rats sustaining delayed fluid resuscitation after burn
      shock].
AB  - Delayed fluid resuscitation of burn shock may lead to many harmful effects. We
      investigated the injury of heart of burned rats having no fluid resuscitation,
      immediate and delayed fluid replacement. We used electron spin resonance (ESR) to
      determine the presence of oxygen free radicals (OFR). We also found significant
      increase in malondialdehyde (MDA) in delayed resuscitation group. The activity of
      lactate dehydrogenase isoenzyme (LDH) and creatine phosphokinase isoenzyme (CPK
      MB) were increased in the latter group. Immediate fluid replacement can not
      protect the heart perfectly. Some new measure should be added to the fluid
      replacement in burn shock.

PMID- 7648497
TI  - [Myocardial damage after high tension electricity injury in rabbits].
AB  - The experiment was designed to study the condition of rabbit myocardium after
      10,000-Volt high tension electricity injury by using light and electron
      microscopes. Early change in myocardium was detected and it took a dynamic
      development. Also, the enzymogram of myocardium was found to be altered parallel
      with the pathological alteration, apart from significant changes showed in
      electrocardiograms. The result of the study demonstrated that organic injury
      occurred in myocardium after high tension electricity injury.

PMID- 7648498
TI  - [Qualitative observation and quantitative survey on the vasculature of the
      lateral thoracic region].
AB  - Since 1988, we had studied blood vessels on the lateral thoracic region in 21
      patients using ultrasound Doppler flowmeter preoperatively, collaborating with
      operative observation, to measure the length, caliber and rate of existence of 3
      main vascular systems. Our study attempted both to ascertain various regular
      patterns of vasculature, and to provide anatomical data for the choice of proper
      sites of pedicles of lateral thoracic flap. Our findings showed that the
      subscapular-thoracodorsal vascular system was the most constant among the 3
      systems. Its average length was 15.43 +/- 0.504 cm, average diameter at its
      origin was 1.58 +/- 0.122 mm. The thoracoepigastric vein as a venous return
      system could be chosen first. We concluded that this method was a handy,
      practical and dependable way to determine the vascularity of lateral thoracic
      flaps.

PMID- 7648499
TI  - [A study of autogenous hair transplantation in Chinese].
AB  - From Sep. 1988 to Dec. 1992, a total of 980 procedures of autogenous punch grafts
      were performed in 395 patients with alopecia. This technique has mainly been used
      for seborrheic alopecia and cicatricial alopecia with sufficient hair in the
      donor site. Chinese people are unfavorably characterized by one-third less amount
      of hair than Westerners, lank hair shaft and strong contrast of color between the
      hair and hair-bearing scalp. The technique of L shape punch grafts was used for
      patients with insufficient hair in the donor site. Insertion of mini-grafts
      between the anterior rows of punch grafts made the frontal hairline more natural
      in appearance and eliminated the necessity of postoperative scalp tattoo. The
      results were perfect. We concluded that adult alopecic patients are good
      candidates for punch graft procedure, and for children and juvenile patients,
      scalp expansion is preferable.

PMID- 7648500
TI  - [Wound repair with the fasciocutaneous flap of double reverse Z-plasty].
AB  - Based on the rich blood supply of deep fascia and the Z-plasty technique, the
      authors have designed an operation using the fasciocutaneous flap of double
      reverse Z-plasty to repair soft tissue defects over joints, anterior tibia, head,
      face or sacrococcygeal region. Utilizing the nearby skin to the maximum, the
      method has produced cosmetically and functionally good results in 21 patients
      since 1990.

PMID- 7648501
TI  - [Experimental observations of the quantitative changes of proteoglycan in
      homogenous cartilage graft in the guinea pig].
AB  - The present work was to study the quantitative change of proteoglycan (PG) in
      homogenous cartilage graft in the guinea pig. Histological, histochemical and
      biochemical studies were undertaken at different times after grafting. The
      results revealed that there was a marked reducing trend of matrix PG within four
      weeks after grafting. Four weeks afterwards all indexes except hexuronic acid
      restored slowly and approached the level of the control group. By the 20th week,
      the activity of neutromucopolysaccharide, hexosamine, acid-mucopolysaccharide and
      alkaline phosphatase restored to 73.6% -93.7% of the control group (P > 0.05).
      The changes probably were caused by immune reaction and operative trauma. PG in
      the cartilage matrix forms a barrier for the chondrocytes, protecting the host's
      immune system from contacting and reacting with the chondrocytes of the graft.
      Though the core protein of PG has antigenicity, it is surrounded by
      acidmucopolysaccharide that has no antigenicity. We concluded that it is very
      important to maintain a high level of PG in order to prolong the survival of a
      cartilage graft.

PMID- 7648502
TI  - [Reduction mammaplasty and mastopexy with a circumareolar incision].
AB  - Since 1990, we have done reduction mammaplasty and mastopexy on 22 patients using
      the circumareolar incision method. The advantages of the operation are as
      follows: simple design, less operative trauma, the possibility of performance
      under local anaesthesia, lactation preserved, good appearance with inconspicuous
      scar.

PMID- 7648503
TI  - [The effect of retinoic acid on DNA synthesis of fibroblast in vitro culture].
AB  - The effect of retinoic acid on DNA synthesis of fibroblast was studied in vitro
      culture. The results demonstrated that retinoic acid significantly (P < 0.01)
      inhibited the DNA synthesis of fibroblast in vitro culture and a dose-dependent
      relationship between DNA synthesis and retinoic acid concentration was observed.
      The possible mechanism of retinoic acid used for the treatment of scar was
      discussed.

PMID- 7648504
TI  - [The effect of extract from dermis on fibroblasts of human skin].
AB  - The author has observed that the extract from normal human dermis has obvious
      inhibitory effects on human skin cultured fibroblasts. The results revealed that
      dermis contains substances which could inhibit growth of fibroblast and that
      their presence could explain the lack of activity of the normal dermis close to
      cicatrization.

PMID- 7648506
TI  - [Retrospects and prospects of the application of microsurgery to plastic
      surgery].

PMID- 7648505
TI  - [Progress in the pathological and molecular biological study on skin aging].

PMID- 7648507
TI  - [Free radical production in the subdermal vascular network thin skin flap].
AB  - In this experiment 12 piglets were used to study the survival length and free
      radical production of subdermal vascular network thin skin flap, fascial flap and
      PSVN. The flap or graft was designed 15 cm x 3 cm in size on the flanks of the
      animals. Twenty-four flaps or grafts were formed in each group. The observation
      on 7 postoperative day indicated that the survival length of the subdermal
      vascular network thin skin flap was 38% over that of fascial flap, while the free
      radical was less in the former, and it could be one of the reasons for its better
      survival.

PMID- 7648508
TI  - [The application of thin subdermal vascular network flap with a pedicle by a
      named vessel for repair of hand defects].
AB  - Thin subdermal vascular network flaps of the hypogastric region were created
      close to inguinal, superficial epigastric or superficial circumflex vessels. They
      were used to repair the defects of the hand in 12 patients. The pedicle was
      divided about one week after the flap transfer. All the flaps survived with
      satisfactory results.

PMID- 7648509
TI  - [The use of thin skin flap with preserved subdermal vascular network in repair of
      the face and neck].
AB  - Since 1989 twenty-one thin flaps with preserved subdermal vascular network of the
      neck, shoulder or pectoral region have been used in 18 cases with severe scar
      contracture of the neck. The size of the flaps ranged from 10 cm x 2 cm to 20 cm
      x 8 cm and the pedicles were 3.5 to 4 cm in width. Our results proved the
      reliability of this method. The blood supply of the flap, the design and
      indications of the operation are discussed.

PMID- 7648510
TI  - [The application of thin skin flap with a preserved subdermal vascular network in
      12 cases].

PMID- 7648511
TI  - [Effects of glucocorticoid on PMN adhesion induced by TNF].
AB  - TNF was used as a stimulating factor to study the effects of glucocorticoid (GC)
      on polymorphonuclear leucocyte (PMN) adhesion. The results showed that tumor
      necrosis factor (TNF) could increase the PMN adhesion markedly, and Dex could not
      inhibit the PMN adhesion induced by TNF, but it had a certain effect of
      prevention. PMN adhesion was increased prominently when Dex and RU 38486 were
      given after TNF pretreatment.

PMID- 7648512
TI  - Pharmacogenetics in clinical pharmacology and toxicology.
AB  - This subject was particularly important to discuss in the presence of Werner
      Kalow, 77 years young, who is considered as one of the grandfathers of this
      unique combination of medical research fields. It has become increasingly
      appreciated that dozens of human drug metabolism polymorphisms exist. The
      interindividual variabilities in drug metabolism discussed at this symposium do
      not represent small differences such as 50% or 3-fold but, rather, represent 10-
      to greater than 1000-fold differences. When attributed to a single gene, dramatic
      differences can be seen among family members, just as blue and brown eyes can
      occur in siblings. These differences can result in acute drug toxicity. In
      addition, there are chronic effects: over one's lifetime, striking differences in
      the metabolism of drugs, occupationally hazardous chemicals, and other
      environmental pollutants can lead to interindividual differences in the buildup
      of DNA damage (e.g., mutations, chromosomal breaks, rearrangements) leading to
      toxicity and tumor initiation, as well as leading to a buildup in nongenotoxic
      signals (signal transduction pathways without DNA damage) important for toxicity,
      tumor promotion, and tumor progression. The human UDP glucuronosyltransferase
      (UGT superfamily is known to comprise more than 10 genes in humans, and probably
      in other mammalian species. Breakthroughs in UGT gene mutations responsible for
      the Crigler-Najjar syndrome and Gilbert's disease have recently been reported.
      The human cytochrome P450 termed CYP3A4 is a major P450 enzyme in the liver and
      gastrointestinal tract, and the full impact of the CYP3A4 polymorphism has yet to
      be fully appreciated.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7648513
TI  - Circadian variations of adenosine and of its metabolism. Could adenosine be a
      molecular oscillator for circadian rhythms?
AB  - The present review describes the biological implications of the periodic changes
      of adenosine concentrations in different tissues of the rat. Adenosine is a
      purine molecule that could have been formed in the prebiotic chemical evolution
      and has been preserved. The rhythmicity of this molecule, as well as its
      metabolism and even the presence of specific receptors, suggests a regulatory
      role in eukaryotic cells and in multicellular organisms. Adenosine may be
      considered a chemical messenger and its action could take place at the level of
      the same cell (autocrine), the same tissue (paracrine), or on separate organs
      (endocrine). Exploration of the circadian variations of adenosine was planned
      considering the liver as an important tissue for purine formation, the blood as a
      vehicle among tissues, and the brain as the possible acceptor for hepatic
      adenosine or its metabolites. The rats used in these studies were adapted to a
      dark-light cycle of 12 h with an unrestrained feeding and drinking schedule. The
      metabolic control of adenosine concentration in the different tissues studied
      through the 24-h cycle is related to the activity of adenosine-metabolizing
      enzyme: 5'-nucleotidase adenosine deaminase, adenosine kinase, and S
      adenosylhomocysteine hydrolase. Some possibilities of the factors modulating the
      activity of these enzymes are commented upon. The multiphysiological action of
      adenosine could be mediated by several actions: (i) by interaction with
      extracellular and intracellular receptors and (ii) through its metabolism
      modulating the methylation pathway, possibly inducing physiological
      lipoperoxidation, or participating in the energetic homeostasis of the cell. The
      physiological meaning of the circadian variations of adenosine and its metabolism
      was focused on: maintenance of the energetic homeostasis of the tissues,
      modulation of membrane structure and function, regulation of fasting and feeding
      metabolic pattern, and its participation in the sleep-wake cycle. From these
      considerations, we suggest that adenosine could be a molecular oscillator
      involved in the circadian pattern of biological activity in the rat.

PMID- 7648515
TI  - Body temperature regulation in rats near term of pregnancy.
AB  - Experiments were carried out to define the effects of pregnancy on body
      temperature (Tb) regulation in rats. Tb was measured by biotelemetry in six
      animals from day 10 of pregnancy (term day 21) to postpartum day 10. Average 24-h
      Tb decreased from day 15 of gestation to the time of parturition. Furthermore,
      there was a loss of the normal circadian variation of Tb late in gestation, which
      was again present by postpartum day 2. The decrease in 24-h Tb on day 15 of
      gestation resulted from this loss of circadian variation, as Tb did not increase
      during the dark period. The further decrease in Tb on day 20 of gestation
      resulted from an overall decrease in Tb during the light and dark periods as well
      as from a loss of the circadian variation in Tb. Tb increased dramatically within
      4 h of birth of the first pup, which always occurred on day 21 during the light
      period. The mechanisms responsible for these dramatic changes in thermoregulation
      during late gestation and around the time of parturition are presently unknown.

PMID- 7648514
TI  - Phasic contractions of the muscular components of human esophagus and
      gastroesophageal junction in vitro.
AB  - This study was performed to assess the repetitive phasic mechanical and (or)
      electrical activity of the muscle from different regions of the human
      gastroesophageal junction (GEJ). Muscle strips from the circular and longitudinal
      layers of the gastric fundus and esophagus and of the clasp and sling components
      of the GEJ were obtained from surgical specimens and prepared for in vitro
      recording of contractile or electrical activity. Phasic contractions occurred in
      all regions except the longitudinal muscle of the gastric fundus and that
      overlying the sling. Robust phasic activity (2.6 +/- 0.6 min-1) was most frequent
      (92% of specimens) in longitudinal muscle overlying the clasp, arising
      spontaneously in 67%. Stretch or carbachol stimulation increased the frequency of
      these contractions. Transmural electrical stimulation produced a transient
      cessation of phasic activity. Electrical recording showed slow waves with
      superimposed spiking coinciding with phasic contractions. These activities were
      unaltered by 1 microM atropine or 1 microM tetrodotoxin, but inhibited by 2
      microM verapamil. In conclusion, several muscles of the human esophagus and GEJ
      manifest repetitive contractions in vitro, particularly the longitudinal muscle
      overlying the clasp muscle fibers. These oscillations are due to electrical slow
      waves, can potentially be modulated by intrinsic nerves, and may play a role in
      the intermittent phasic contractions of lower esophageal sphincter pressure in
      vivo.

PMID- 7648516
TI  - Myocardial lipoprotein lipase activity: regulation by diabetes and fructose
      induced hypertriglyceridemia.
AB  - The decrease in myocardial lipoprotein lipase (LPL) activity observed previously
      in acute, severe models of insulin-deficient diabetes may be a compensatory
      response to hypertriglyceridemia and a sustained increase in fatty acid delivery
      to cardiomyocytes. The administration of fructose (10% solution in the drinking
      water for 4 days) to rats produced hypertriglyceridemia, but heparin-releasable
      LPL activity from perfused hearts and total and heparin-releasable LPL activities
      in isolated cardiomyocytes were not reduced. The acute (4 day) induction of a
      mild diabetic state (60 mg/kg streptozotocin) resulted in modest
      hypertriglyceridemia, and a selective decrease in heparin-releasable LPL activity
      in perfused hearts; LPL activity in cardiomyocytes from diabetic rat hearts was
      not reduced. Therefore, the diabetes-induced fall in myocardial LPL activity is
      not secondary to hypertriglyceridemia, since fructose treatment did not change
      LPL activity. Perfusion of rat hearts with 100 microM lysophosphatidylcholine
      (LPC) released a small amount of LPL activity into the perfusate, but only if
      albumin was omitted from the perfusion solution. Thus, the selective reduction in
      heparin-releasable LPL activity in perfused diabetic hearts is probably not the
      consequence of displacement by LPC, a lipolytic product of the LPL-catalyzed
      degradation of triacylglycerol-rich lipoproteins. Circulating LPL activity in the
      plasma of diabetic rats was not decreased relative to control plasma enzyme
      activity; therefore, the reduction in heparin-releasable LPL activity is not
      because circulating LPL was less available for uptake by the endothelium in
      diabetic hearts.

PMID- 7648517
TI  - Decreased vascular contractile and inositol phosphate responses in portal
      hypertensive rats.
AB  - The purpose of this study was to investigate the vascular contractile and
      inositol phosphate responses in portal hypertensive rats. Portal hypertension was
      induced by partial portal vein ligation (PVL) in Sprague-Dawley rats. Sham
      operated rats served as controls. Pressures, vasoconstrictor responses, and
      inositol phosphate responses were determined at 14 days after surgery. The portal
      venous pressure was significantly higher, while systemic arterial pressure and
      heart rate were lower, in PVL rats. Dose-dependent contractile responses were
      observed for both norepinephrine (1 x 10(-8) - 3 x 10(-6) M) and vasopressin (3 x
      10(-10) - 3 x 10(-8) M) in the tail artery of both groups. The contractile
      response to norepinephrine was significantly decreased in PVL rats compared with
      controls at all doses. The contractile response to vasopressin was significantly
      decreased in PVL rats at higher doses. After myo-[3H]inositol incorporation in
      tail artery, the levels of 3H-labelled phosphatidylinositols (cpm/mg) were
      similar between the two groups. Norepinephrine (10(-7) - 10(-5) M) and
      vasopressin (10(-10) - 10(-8) M) dose dependently stimulated the 3H-labelled
      inositol phosphate production in the tail artery of both PVL and sham-operated
      rats. However, the response was significantly lower in PVL rats. The results
      suggested that the attenuation of vascular contractile responses in portal
      hypertension was reflected in the phosphoinositide messenger system.

PMID- 7648518
TI  - Cardiovascular effects of N-methyl leukotriene C4, a nonmetabolizable leukotriene
      C4 analogue, and the antagonism of leukotriene-induced hypotension by Ro 23-3544,
      in the American bullfrog, Rana catesbeiana.
AB  - Although some leukotriene antagonists have been reported to block leukotriene
      (LT) C4 responses in vivo, it is difficult to determine whether those antagonists
      block the effect of LTC4 directly or act via blocking the action of LTD4, as LTC4
      is metabolized to LTD4 rapidly in vivo. In this study, the dose-response curves
      of N-methyl LTC4 (NMLTC4), the nonmetabolizable LTC4 analogue, and the
      peptidoleukotrienes (LTC4, LTD4, and LTE4) were obtained in the absence and
      presence of the leukotriene antagonist Ro 23-3544 in cannulated frogs. The more
      potent effect of NMLTC4 suggests that receptors that preferentially bind LTC4
      exist in frog vascular smooth muscle and the previously reported LTC4 effect is a
      combination of LTC4 and its less potent metabolite LTD4. The NMLTC4- and LTC4
      induced hypotensive effects were antagonized by Ro 23-3544. Ro 23-3544 also
      antagonized the effects induced by high doses of LTD4 and LTE4. Ro 23-3544 had no
      effect on duration of response and did not affect heart rate responses to LTC4 at
      low dose of the antagonist. The data suggest that receptors that preferentially
      bind LTC4 in bullfrog vascular smooth muscle regulate the hypotensive effect and
      that they can be antagonized by Ro 23-3544.

PMID- 7648519
TI  - Neurophysiological consequences of nitroxide antioxidants.
AB  - Nitroxides are antioxidant compounds that have been shown to provide
      radioprotection in vivo and in vitro. Radioprotection in vivo is limited by
      toxicity, which appears to be neurologic in nature. To further evaluate the
      toxicity of these compounds, three representative nitroxides, Tempol, Tempamine,
      and Tempo, were examined in slices of guinea pig hippocampus. Each nitroxide
      increased the population spike and caused potentiation of excitatory postsynaptic
      potential--spike coupling. Repetitive activity and epileptiform activity were
      observed at the highest concentrations of Tempo and Tempamine. Tempol was the
      least toxic compound in this system, followed by Tempamine and Tempo. Additional
      studies are necessary to further define the effects of nitroxides on the central
      nervous system and to develop strategies to mitigate these effects.

PMID- 7648520
TI  - Endothelium derived relaxing factor release from canine coronary artery by
      leukocytes.
AB  - Lectins, known to recognize endothelial cell adhesion molecules, have been shown
      to release endothelium-derived relaxing factor (EDRF) from blood vessels. We
      investigated the effects of different leukocyte-type cells to determine if these
      cells, by interacting with the endothelium, could release EDRF from the
      circumflex branch of the canine coronary artery. The following cells were
      investigated: human promyelocytic leukemia (HL-60), human monocyte (THP-1), and
      human Burkitt lymphoma (DAUDI). All of these cells produced a significant
      endothelium-dependent relaxation of the dog coronary artery in the presence of
      ibuprofen. The endothelium-dependent relaxations were reversed by hemoglobin (10
      microM), methylene blue (3 microM), 6-anilino-5,8-quinolinedione (LY 83583, 30
      microM), and NG-nitro-L-arginine methyl ester (L-NAME, 1 mM). HL-60 cells grown
      in the presence of 1 mM L-NAME retained their ability to cause endothelium
      dependent relaxation of the canine coronary artery, suggesting that the source of
      the NO was the endothelium and not the HL-60 cells. The cell-induced vascular
      relaxation could be obtained in the absence of extracellular calcium. It is
      suggested that HL-60, THP-1, and DAUDI cells interact with a specific receptor on
      the endothelial cell and as a result of this interaction the endothelial cells
      are stimulated to release EDRF.

PMID- 7648521
TI  - Comparison of dot blot hybridization, polymerase chain reaction, and virus
      isolation for detection of bovine herpesvirus-1 (BHV-1) in artificially infected
      bovine semen.
AB  - Bovine semen samples spiked with bovine herpesvirus 1 (BHV-1) were used to
      compare dot blot hybridization, polymerase chain reaction (PCR), and virus
      isolation for detection of BHV-1 in bovine semen. The PCR amplification used
      primers targeting the BHV-1 thymidine kinase gene and a nucleic acid releasing
      cocktail (GeneReleaser); the PCR product was used as the DNA probe in dot blot
      hybridization; virus isolation was done in primary bovine fetal testis (BFT) cell
      cultures. Semen diluted 1:20 in tissue culture medium had the least cytotoxicity
      and inhibition of viral cytopathic effects in BFT cells, allowing detection of 1
      TCID50/100 microL of BHV-1 suspension by virus isolation. The presence of foreign
      DNA such as bovine sperm DNA or salmon sperm DNA increased the sensitivity of dot
      blot hybridization in detecting BHV-1, allowing detection of 20,000 TCID50/100
      microL of neat semen. The inhibition of PCR amplification of BHV-1 DNA in bovine
      semen was eliminated by diluting the samples 1:20 in tissue culture medium. The
      best PCR amplification was obtained when semen was diluted 1:20 and when a
      reaction buffer of pH 9.0, with 1.0 mM MgCl2 was used. Under these conditions,
      the PCR followed by ethidium bromide staining of agarose gels could detect 1
      TCID20/100 microL of sample, whereas PCR followed by Southern blot hybridization
      could detect 0.01 TCID50/100 microL of sample.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7648522
TI  - Dissociation of cytolysis and monokine release by bovine mononuclear phagocytes
      incubated with Pasteurella haemolytica partially purified leukotoxin and
      lipopolysaccharide.
AB  - The bovine respiratory pathogen Pasteurella haemolytica secretes an exotoxin that
      is specific for ruminant leukocytes (leukotoxin). Previous studies have shown
      that subcytolytic concentrations of the leukotoxin stimulate bovine neutrophils
      to undergo a respiratory burst and degranulate. Relatively little is known about
      the stimulatory effects of the leukotoxin on bovine mononuclear phagocytes. In
      this study, we compared the relative cytolytic effects of partially purified
      leukotoxin on bovine peripheral blood monocytes and alveolar macrophages. We
      found monocytes to be approximately 8- to 10-fold more sensitive than alveolar
      macrophages to the cytolytic effect of leukotoxin. In addition, incubation of
      monocytes and alveolar macrophages with sublethal doses of leukotoxin stimulated
      release of IL-1 and TNF activities in a dose-dependent manner. Addition of an
      antileukotoxin MAb neutralized the cytolytic effects of leukotoxin, but
      potentiated TNF release. Heat inactivation also blocked the cytolytic activity of
      LKT, but only slightly reduced its ability to stimulate TNF release. Although the
      leukotoxin preparations were estimated to have only small amounts of
      lipopolysaccharide (LPS) contamination, as determined by a standard Limulus
      amebocyte lysate coagulation assay, a chromogenic Limulus assay indicated much
      greater amounts of LPS were present. Adding equivalent doses of P. haemolytica
      LPS largely duplicated the monokine release stimulated by leukotoxin. These
      results suggest that the stimulatory effects of the P. haemolytica leukotoxin on
      bovine mononuclear phagocytes may principally involve LPS, perhaps complexed with
      leukotoxin.

PMID- 7648523
TI  - Interaction with pig ileal explants of Escherichia coli O45 isolates from swine
      with postweaning diarrhea.
AB  - We have previously observed that Escherichia coli O45 isolates from swine
      postweaning diarrhea (PWD) induced attaching-effacing (A/E) lesions in
      experimentally inoculated gnotobiotic piglets. In the present work, ileal explant
      culture has been used as an in vitro model for the study of the development of
      A/E lesions due to these isolates. The characteristic intimate bacterial
      attachment and microvilli effacement with cupping and pedestal formation,
      identical to that observed in gnotobiotic piglets, was demonstrated in pig ileal
      explants inoculated with O45 E. coli isolates. The initial attachment of bacteria
      to the enterocytes was observed from 2 to 4 h postinoculation (PI) and full
      development of A/E lesions was observed within 8 h PI. In this model, we observed
      that 22 of 25 eaeA-positive O45 isolates induced A/E lesions. However, A/E
      lesions were not observed for any of 7 eaeA-negative O45 isolates. Thus, we
      describe a useful in vitro model for the study of A/E capacity of porcine E.
      coli. Use of this model has enabled us to demonstrate the relatedness of the eaeA
      gene to A/E capability among porcine O45 E. coli from PWD.

PMID- 7648525
TI  - Tear copper and its association with liver copper concentrations in six adult
      ewes.
AB  - Tear and liver copper concentrations from 6 clinically healthy adult mixed-breed
      ewes were measured by Atomic Absorption Electrothermal Atomization (graphite
      furnace) Spectrometry and Flame Absorption Spectrometry, respectively, 7 times
      over 227 d to determine if their tears contained copper and if so, whether tear
      copper concentrations could reliably predict liver copper concentrations. To
      produce changes in liver copper concentration, the diet was supplemented with
      copper at concentrations that increased from 23 mg to 45 mg Cu/kg feed/day/sheep
      during the study. This regimen raised liver copper for all sheep to potentially
      toxic hepatic tissue concentration of greater than 500 mg/kg dry (DM) matter
      (tissue). The results of the study showed that copper was present in the tears of
      all sheep. The mean tear copper concentration showed a positive correlation with
      liver copper concentration (P = 0.003), increasing from 0.07 mg/kg DM at the
      start to 0.44 mg/kg DM at the end of the study, but could not reliably predict
      liver copper concentration (R2 = 0.222).

PMID- 7648524
TI  - Prevalence of coagulase gene polymorphism in Staphylococcus aureus isolates
      causing bovine mastitis.
AB  - This study was conducted to investigate polymorphism of the coagulase gene of
      Staphylococcus aureus causing bovine mastitis. One hundred eighty-seven strains
      of S. aureus were isolated from bovine mastitic milk samples obtained from 187
      different Danish dairy farms. The isolates were characterised for restriction
      fragment length polymorphism (RFLP) of the coagulase gene. A variable region of
      the coagulase gene was amplified using the polymerase chain reaction (PCR)
      followed by AluI restriction enzyme digestion. A total of 15 different RFLP
      patterns were observed. The predominant pattern was found in 35% of the isolates.
      The ease of analysing coagulase gene polymorphisms among a large number of
      strains, and the multiple distinct polymorphic patterns generated, supports the
      use of this technique in epidemiological investigations of bovine mastitis. The
      predominating variants may have predelection for causing intramammary infections.

PMID- 7648526
TI  - Comparative assessment of right ventricular performance from the pressure-volume
      relationship in double-muscled and conventional calves.
AB  - Forty-one and 55 records of right-sided and systemic arterial pressures, cardiac
      output, and end-diastolic and end-systolic right ventricular volumes were
      collected from a group of 6 conventional and 6 double-muscled calves,
      respectively. In each group, the mean right ventricular pressure-volume loop was
      constructed. Global cardiac performance was significantly lower in the double
      muscled than in the conventional calves. The right ventricular end-diastolic and
      end-systolic volumes, as well as the diastolic portion of the mean pressure
      volume loop, were similar in the 2 groups. Those results suggest that the reduced
      cardiac performance of double-muscled calves is not due to a lowered ventricular
      preload and that diastolic properties of their myocardium are similar to those of
      conventional calves. When expressed on a body weight basis, however, the right
      ventricular end-diastolic and end-systolic volumes were lower in the double
      muscled than in conventional calves. When expressed as a function of probable
      metabolic demand, therefore, the volumetric capacity of the cardiac pump appears
      to be reduced in double-muscled calves. The significantly lower right ventricular
      ejection fraction, maximal rate of ventricular pressure rise and right
      ventricular peak-systolic pressure to end-systolic volume ratio measured in
      double-muscled as compared with conventional calves suggest that reduced
      myocardial contractility may also be partly responsible for the significantly
      lower stroke index of the former calves. The cardiac pump of double-muscled
      cattle thus seems to be less effective than that of conventional cattle because
      of reduced volumetric capacity and lowered strength of contraction.

PMID- 7648527
TI  - Evaluation of an O antigen enzyme-linked immunosorbent assay for screening of
      milk samples for Salmonella dublin infection in dairy herds.
AB  - Levels of antibodies to the O antigens (O:1,9,12) of Salmonella dublin were
      tested in 1355 serum, 1143 cow milk and 160 bulk milk samples from dairy herds
      using an enzyme-linked immunosorbent assay (ELISA). In order to define the
      background reaction, milk samples from all lactating cows and serum samples from
      9 animals were collected in each of 20 salmonellosis-free herds located on the
      island of Bornholm, where cattle salmonellosis has not been reported. Similar
      samples were collected from all stalled animals in 10 herds with recent (< 6
      months) outbreaks of salmonellosis located in Jutland, where salmonella infection
      is enzootic. Using herd history of salmonellosis, herd location and clinical
      status of the herds as criteria, the optimal cutoff in the milk ELISA was
      determined as being at least 5% of the samples having optical density > 0.5,
      resulting in herd sensitivity of 1.0 and herd specificity of 0.95. While none of
      the sera in the herds from Bornholm was ELISA positive, 2 herds had a few
      reactors in the milk ELISA. Using the same cutoff, all but 1 bulk milk sample
      from 150 herds on Bornholm was ELISA-negative, and all 10 salmonellosis-positive
      herds from Jutland were ELISA-positive. A significant correlation was found
      between ELISA reactions in milk and in serum of cows (34% and 32% respectively,
      rs = 0.69, P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7648528
TI  - Growth of Serpulina (Treponema) hyodysenteriae under iron-restricted conditions.
AB  - Reference strains of Serpulina hyodysenteriae expressed at least three iron
      regulated proteins with apparent molecular masses of > 200, 134, and 109 kDa when
      grown under iron-restricted conditions. Cells of S. hyodysenteriae grown under
      these conditions also showed increased outer membrane bleb formation when
      examined by electron microscopy after negative staining. S. hyodysenteriae did
      not use the 2 most common types of siderophore, namely catechol and hydroxamate.
      Western blotting with serum from a pig experimentally infected with S.
      hyodysenteriae B204 indicated that the 109-kDa major iron-regulated protein was
      expressed in vivo and was conserved among all strains tested.

PMID- 7648529
TI  - Pasteurella multocida toxin induces IL-6, but not IL-1 alpha or TNF alpha in
      fibroblasts.
AB  - Pasteurella multocida toxin (PMT) is the major virulence factor in Progressive
      Atrophic Rhinitis of swine. Other workers' previous findings that PMT was
      mitogenic for 3T3 fibroblasts, were confirmed in the present study. In addition,
      PMT stimulated 3T3 cells to release IL-6, but IL-1 alpha or TNF alpha were not
      detected in fibroblast supernatants sampled 24, 48, or 72 h after stimulation. In
      view of the role of IL-6 in osteoclastic bone resorption, these findings provide
      a new working hypothesis for investigations into the molecular pathogenesis of
      this important disease.

PMID- 7648530
TI  - In vitro assessments of the genetic stability of a live recombinant human
      adenovirus vaccine against rabies.
AB  - The genetic stability of a live human adenovirus 5: rabies glycoprotein
      recombinant vaccine has been assessed upon 20 serial passages in a permissive
      cell line of human origin. Restriction endonuclease analysis and the polymerase
      chain reaction were used to examine the integrity of the expression cassette for
      the rabies glycoprotein and the viral vector at the site of insertion of the
      cassette. It was found that the restriction endonuclease profile was identical
      for each sample assayed. A more detailed analysis of the expression cassette
      following amplification by the polymerase chain reaction revealed no changes in
      the size and number of fragments originating from the coding sequence for the
      glycoprotein nor the signals controlling the expression of the protein product.
      The amplified product obtained from the 10th and 20th passages was subjected to
      nucleotide sequencing. Additionally, 20 plaques isolated from the 20th passage of
      the virus expressed the rabies glycoprotein as demonstrated by fluorescent
      antibody staining with glycoprotein specific monoclonal antibodies. These results
      suggest that the recombinant vaccine maintains the integrity of the heterologous
      sequences upon passage in tissue culture.

PMID- 7648532
TI  - The prevalence of bovine viral diarrhea virus infection in a population of
      feedlot calves in western Canada.
AB  - The prevalence of bovine viral diarrhea virus (BVDV) infection was examined in a
      population of 5129 recently weaned steer calves entering a large feedlot in
      central Saskatchewan from September to December 1991. Serum samples were
      collected within 24 h of arrival at the feedlot from every fifth calf processed
      and again 96 d postarrival. A microtiter virus isolation test was used to
      determine the prevalence of calves viremic with BVDV on entry to the feedlot. An
      enzyme-linked immunosorbent assay (ELISA) which detects antibody against
      glycoprotein 53 of the BVDV was used on paired sera to determine the
      seroconversion risk during the first 96 d in the feedlot. A virus neutralization
      (VN) test for BVDV was conducted on a sub-sample of paired sera to measure
      agreement in determination of seroconversion risk with the ELISA. A polymerase
      chain reaction (PCR) test which detects BVDV was used to determine if cattle were
      acutely viremic when treated for disease. The estimated prevalence of
      persistently infected calves in this population was < 0.1%. The seroconversion
      risk for BVDV was 27% (236/864) according to the ELISA and it varied from 0 to
      63% among the 20 pens sampled. According to the VN test, the seroconversion risk
      for BVDV was 40% (132/327) and it varied from 0 to 100% among the 11 pens tested.
      The agreement between the ELISA and VN tests in seroconversion risk to BVDV was
      very poor (kappa = 0.15 +/- 0.039 SE). The prevalence of acute viremia in calves
      treated at the feedlot hospital was low at 4% (6/149).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7648533
TI  - Establishment of conditions for the detection of bovine herpesvirus-1 by
      polymerase chain reaction using primers in the thymidine kinase region.
AB  - Polymerase chain reaction (PCR) for detection of bovine herpesvirus-1 (BHV-1) was
      developed and optimized using 22 bp sense and 20 bp antisense primers in the
      thymidine kinase (TK) coding region. The amplification product is 183 bp long.
      The PCR optimization was done using BHV-1 tissue culture supernate (BHV-1TCS),
      concentrated BHV-1 tissue culture supernate (cBHV-1TCS) and sucrose gradient
      purified BHV-1 (pBHV-1). The sensitivity of four methods of sample preparation
      which are standard DNA extraction, modified proteinase K (PK) digestion,
      GeneReleaserTM + 34 cycles or + 44 cycles, and boiling were compared with virus
      isolation (VI) using BHV-1TCS. The incorporation of 10% glycerol in the reaction
      mixture, the incubation in PK for 18 hours and predenaturation of samples and
      cooling in ice prior to PCR were essential for the amplification of BHV-1 DNA for
      samples prepared by standard DNA extraction and modified PK digestion. The
      preparation of samples by Gene-ReleaserTM, a proprietary nucleic acid releasing
      cocktail, showed 10 to 1,000-fold increase in sensitivity compared to standard
      DNA extraction and modified PK digestion. No amplification was observed in
      samples prepared by boiling. The sample preparation of BHV-1 LA strain by
      GeneReleaserTM showed sensitivity equivalent to virus isolation. The BHV-1 TK PCR
      using GeneReleaserTM has a detection limit of 1 picogram and 10 fentograms of
      purified BHV-1 DNA using ethidium bromide stained gel and Southern blot
      hybridization, respectively. It could detect viral DNA in 1,000 infected cells in
      a total suspension of 10,000 cells using either ethidium bromide stained gel or
      Southern blot hybridization.

PMID- 7648531
TI  - Prevalence of bovine parvovirus infection in Ontario dairy cattle.
AB  - Studies were conducted to determine prevalence and dynamics of bovine parvovirus
      (BPV) infection. Dairy cows from 29 randomly selected herds in southwestern
      Ontario were tested twice, one year apart, for the presence of hemagglutination
      inhibition (HI) antibodies against BPV. Fifty-one percent of 1141 cows tested had
      BPV-HI titers > 1:32. One year later, the seroprevalence was 83% in 1131 cows
      from the same farms. The herd mean seroprevalence was 49% and 86% for the year-1
      and year-2 samples, respectively. Evidence of BPV infection was found in 96%
      (27/28) of herds in year-1 and 100% of herds in year-2. A comparison of titers
      from 716 cows tested twice showed evidence of frequent BPV infection. Sixty-two
      percent of 326 animals selected in a systematic manner from 40 Guelph area dairy
      farms had BPV-HI titers > 1:32. The herd mean seroprevalence was 64% Two herds
      had no animals with titers above the critical titer (1:32) while in one-quarter
      of the herds all animals exceeded the critical titer.

PMID- 7648535
TI  - Selection of students for veterinary medicine--a reply.

PMID- 7648534
TI  - Cross-Canada Disease Report in need of support.

PMID- 7648536
TI  - Shortage of rural, mixed animal practitioners--replies.

PMID- 7648537
TI  - Shortage of rural, mixed animal practitioners--replies.

PMID- 7648538
TI  - An ethicist's commentary on the case of the female veterinarian receiving
      unwelcome attention from her employer.

PMID- 7648539
TI  - Candida krusei isolated from a sporadic case of bovine mastitis.

PMID- 7648540
TI  - Low flow anesthesia revisited.

PMID- 7648543
TI  - Spermatic granulomas in a vasectomized ram.

PMID- 7648541
TI  - Bovine viral diarrhea virus: biotypes and disease.
AB  - Bovine viral diarrhea virus continues to produce significant economic losses for
      the cattle industry and challenges investigators with the complexity of diseases
      it produces and the mechanisms by which it causes disease. This paper updates and
      attempts to clarify information regarding the roles of noncytopathic and
      cytopathic bovine viral diarrhea viruses in persistent infections and mucosal
      disease. It also covers, in brief, what is known of the new diseases:
      thrombocytopenia and hemorrhagic disease, and a disease resembling mucosal
      disease that is apparently caused solely by noncytopathic virus. Although a good
      understanding of the roles of the 2 biotypes in the production of persistent
      infections and the precipitation of mucosal disease has been obtained, there are
      still unanswered questions regarding the origin of cytopathic viruses and the
      mechanism by which they cause pathological changes in cells. It is apparent,
      however, that cytopathic bovine viral diarrhea viruses arise by mutation of
      noncytopathic viruses, and it is known that p80 is the marker protein for
      cytopathic viruses. The previous distinction between mild bovine viral diarrhea
      and fatal mucosal disease has been eroded with the emergence of new virulent
      bovine viral diarrhea viruses. The new diseases pose a threat to the cattle
      industry and present a new challenge for investigators. Index Veterinarius (1984
      1994) and Medline (1985-1994) databases and personal files updated since 1987
      from BIOSIS Previews and Biosciences Information Services were used to search the
      literature.

PMID- 7648542
TI  - The relationship between the presence of Helicobacter pylori, Clostridium
      perfringens type A, Campylobacter spp, or fungi and fatal abomasal ulcers in
      unweaned beef calves.
AB  - A case-control study involving 30 unweaned beef calves was conducted to determine
      whether specific species of bacteria or fungi were associated with fatal abomasal
      ulcer formation. Special microbiological and histological techniques were used to
      detect Clostridium perfringens type A, Helicobacter pylori, or Campylobacter spp.
      It has been speculated that these bacteria are potential ulcerogenic agents of
      unweaned beef calves. Calves were recruited for the study at necropsy, with those
      dying of either a perforating or a hemorrhagic ulcer representing the cases, and
      calves of a similar age dying of a disease unrelated to the abomasum representing
      the controls. Helicobacter pylori was not visualized in or cultured from any of
      the abomasal tissue samples. Clostridium perfringens type A was isolated from
      78.6% of the cases and 75% of the controls. These isolates were further
      dichotomized into "heavy" and "light" growth; no significant association was
      found between ulcers and the amount of growth. A light growth of Campylobacter
      spp. was recovered from 3 cases and 3 controls. There was no compelling evidence
      to suggest that Clostridium perfringens type A, Helicobacter pylori, or
      Campylobacter spp. were involved in ulcer formation.

PMID- 7648544
TI  - Multiple (more than two thousand) epidermal inclusion cysts in a dog.

PMID- 7648546
TI  - Elucidating dental jargon.

PMID- 7648545
TI  - History and clinical signs. Bilateral exophthalmos, and left lagophthalmos and
      corneal ulceration.

PMID- 7648547
TI  - Serological study of a modified-live virus IBR vaccine given to feedlot calves
      after arrival.

PMID- 7648548
TI  - What is your diagnosis?

PMID- 7648549
TI  - Managed care: cookbook medicine, or quality, cost-effective care?

PMID- 7648550
TI  - [Aortocoronary bypass].

PMID- 7648551
TI  - Career development of military nurses.

PMID- 7648552
TI  - Pregnant women and smoking.
AB  - One study estimates that smoking cessation programs for pregnant women could
      prevent several thousand low birthweight babies and save numerous lives each
      year. Cessation must be encouraged and supported at any point during pregnancy.

PMID- 7648553
TI  - What is health promotion?
AB  - With change abounding in Canada's health care system, nurses must redefine their
      roles. One role is in health promotion, a field where nurses have created a
      unique identity for themselves. But before advocating, the concept must be fully
      understood.

PMID- 7648554
TI  - Targeting seniors.
AB  - Health promotion is not just for the young. There has been far too much emphasis
      on the so-called burden that Canada's aging population puts on our health care
      system. It's time we focused on keeping our seniors well.

PMID- 7648555
TI  - [A systems approach to teaching intravenous therapy].
AB  - Nursing students at the college level must master specific techniques related to
      their profession. Some techniques, including those associated with intravenous
      (I.V.) therapy, present unique learning challenges because of their complexity.
      This article offers a teaching strategy based on the main scientific principles
      of I.V. therapy. The authors recommend a systems-based approach that was
      successfully tested by nursing students during the theoretical portion of their
      studies. This strategy relies on the use of concepts, experimental learning,
      simulation and role playing. The theory portion uses diagrams to establish links
      between the various subjects and concepts initially learned by the student. Then,
      based on the individual's learning processes, more specific information is added
      during the motivation, acquisition and performance phases. The article elaborates
      on the development of this strategy.

PMID- 7648556
TI  - A positive approach to menopause.
AB  - In a society that glorifies youth and beauty, the transition through menopause
      can cause needless anxiety and apprehension for many women. Nurses can have
      positive influence on these women by being knowledgeable about the numerous
      causes of stress--physical, psychological, sociocultural and developmental--that
      menopausal women face. Providing them with appropriate information whether at the
      bedside, in the community or around the kitchen table can lead to a better
      perception and acceptance of this natural life transition.

PMID- 7648557
TI  - Preschool health fairs.
AB  - In Vancouver, as in most metropolitan areas, families with preschoolers (infants
      to five-year-olds) are diverse in language, culture, ethnicity, class and socio
      economic status. Immigration, transiency, very young families, single-parent
      families, poverty and rapid land development are characteristic in some areas.
      Despite this diversity, the community health nurses of the Vancouver health
      department have a mandate to provide early intervention and health promotion
      services for the preschoolers of this population. This has proved to be quite a
      challenge.

PMID- 7648559
TI  - Alternative dispute resolution.

PMID- 7648558
TI  - The shift to wellness.

PMID- 7648561
TI  - Thrown to the edge?

PMID- 7648560
TI  - Clarifying population health.
AB  - "Population health" is the latest buzzword in health policy discussions, and more
      recently used by politicians. In fact, it is currently used to describe a wide
      range of activities. Governments are referring to population health more
      frequently as they try to find ways to reduce pressures on their health care
      systems. Its significance, therefore, cannot be overstated. But does anyone know
      what population health really means?

PMID- 7648562
TI  - Positive ageing.

PMID- 7648563
TI  - Serving and supporting seniors.

PMID- 7648564
TI  - Reminiscence, her way.

PMID- 7648565
TI  - Head injuries in children: a chronicle of a quarter of a century.
AB  - Children aged 0-15 years hospitalized in Geneva for head trauma during the last
      quarter of a century are reviewed. More than half of the severely injured
      children were not from Geneva area. New methods of management have been
      introduced progressively. The cases are divided in four successive time periods
      and classified according to their pathology. A continuous improvement in
      mortality is obvious, decreasing from 29.4% to 2.2%, but climbing again to 15.2%
      in the last period, probably due to more severe pathologies. For the Geneva area
      the mortality decreased progressively from 10.4/100,000 to 3.5/100,000 annually,
      due to better organization and management, but also to a drop in the incidence of
      severe cases from 35.5-13.5/100,000 per year. A decrease in the number of traffic
      accidents is responsible for this. However, the number of handicapped children
      has not changed.

PMID- 7648566
TI  - Enlarging skull fractures in children.
AB  - Large skull fractures are conventionally followed radiographically until healing
      occurs. Fractures which enlarge or remain unhealed are commonly termed
      "leptomeningeal cysts" or "growing skull fractures". This study of ten children
      with this injury and a review of the literature shows that a true leptomeningeal
      cyst is seldom present and that skull fractures do not "grow". Moreover, careful
      history-taking and physical examination will correctly identify all enlarging or
      unhealed skull fractures of childhood without the need for plain radiographs or
      computed tomography of the skull.

PMID- 7648567
TI  - Subdural intracranial pressure monitoring in craniosynostosis: its role in
      surgical management.
AB  - In the management of craniosynostosis subdural intracranial pressure (ICP)
      monitoring has proved a useful and safe means of identifying those children with
      raised ICP who are at risk from its long-term sequelae and who would benefit from
      early surgical intervention. Overnight subdural ICP recordings have been obtained
      in 136 unoperated cases of craniosynostosis. Fifteen patients were studied both
      before and after cranial vault remodelling procedures. ICP was raised (> 15 mmHg)
      in 35%, borderline (10-15 mmHg) in 37% and normal (< 10 mmHg) in 27% of cases.
      Raised ICP was present in 28/53 of the syndromic craniofacial dysostosis cases
      and in 20/83 non-syndromic craniosynostosis cases investigated (P < 0.001).
      Raised mean ICP and periodic plateaux of sustained ICP during sleep were
      particularly associated with the syndromic cases. Of the 15 patients studied
      following cranial vault surgery, 9 showed a reduction in ICP, 3 were unchanged
      and 3 had higher ICP postoperatively. The results of ICP monitoring can
      contribute significantly to formulating a rational and staged surgical management
      plan incorporating the need to normalise ICP and correct the frequently severe
      functional and cosmetic consequences of these disorders.

PMID- 7648568
TI  - Lobar hemorrhages in full-term neonates.
AB  - A chart analysis for a 5-year period through December 1992 identified four full
      term neonates with lobar hemorrhage. Prenatal and obstetrical histories were
      uncomplicated; all infants presented with seizures within 48 h following birth.
      Perinatal asphyxia and isoimmune thrombocytopenia were associated with lobar
      hemorrhage in two children. Although computed tomography was sufficient for
      diagnosis, magnetic resonance evaluation provided assessment of specific cortical
      injury and the age of the hemorrhage. No infant underwent surgical intervention;
      three children reached developmental milestones at a mean follow-up of 3.3 years.

PMID- 7648569
TI  - Neuroimaging studies in children with temporal lobectomy.
AB  - Twenty-eight children with intractable seizures who subsequently underwent a
      temporal lobectomy were studied by electroencephalogram (EEG), prolonged video
      EEG telemetry, computed tomography (CT), magnetic resonance imaging (MRI), and
      single photon emission computed tomography (SPECT) for the localization of
      epileptogenic foci. MRI showed abnormalities indicating epileptogenic foci in
      21/25 patients and a increased signal intensity in 7/11 patients with mesial
      temporal sclerosis (MTS). SPECT showed corresponding abnormalities in 17/22
      patients, including an interictal decrease in regional cerebral blood flow
      corresponding to the epileptogenic zone in 15. CT showed localized abnormalities
      in 16/28. All 12 patients with benign, slow-growing neoplasms showed an
      abnormality on CT scan. In children, MRI is essential in localizing epileptogenic
      abnormalities, especially MTS and cortical dysplasia. SPECT contributes to the
      localization of epileptogenic foci, which are often coincident with EEG
      abnormalities, particularly in single pathology. CT depicts benign neoplasms with
      calcification in the temporal lobe, which are likely to provoke complex partial
      seizures.

PMID- 7648570
TI  - Uncoupling of LCBF and LCGU in two different models of hydrocephalus: a review.
AB  - We have used two different experimental models to examine the relationship
      between local cerebral blood flow and metabolism in hydrocephalus. In our first
      experiments local cerebral blood flow (LCBF) and local cerebral glucose
      utilization (LCGU) were measured by quantitative autoradiographic methods in
      adult rats rendered hydrocephalic, though asymptomatic, by the injection of
      kaolin intracisternally at 3 weeks of age and in control animals. There were no
      significant differences in LCGU or LCBF in any of the 29 areas of grey matter
      examined, including layer IV of the cerebral cortex. Scanning across the cerebral
      cortex revealed an appreciable fall in LCGU and LCBF towards the inside and the
      outside of the mantle in control animals. Hydrocephalus had no significant effect
      on this "transmantle" pattern of reduction in cortical metabolism towards the
      periphery, but in contrast, significantly enhanced the reduction in cortical
      blood flow in 7 out of the 10 cortical regions examined. Hence, in this model of
      asymptomatic hydrocephalus there is relative uncoupling of LCBF and LCGU in the
      inner and outer layers of the cerebral mantle. In a study performed in
      congenitally hydrocephalic H-Tx rats at 10, 20 and 28 days we found that uptake
      of deoxyglucose was impaired in hydrocephalic rats compared with their non
      hydrocephalic siblings. Small changes were seen at 10 and 21 days, but
      statistically significant changes were seen only at 28 days. A small reduction in
      LCBF was observed in all regions at 10 days, with statistically significant
      differences between control and hydrocephalic rats in auditory and parietal
      cortex.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7648571
TI  - Mechanisms and evolution of the brain damage in neonatal post-hemorrhagic
      hydrocephalus.
AB  - There are three main mechanisms of poor outcome in children with post-hemorrhagic
      hydrocephalus: (1) brain injuries due to ventricular dilatation, (2) shunt
      related complications, and (3) primary cerebral hypoxic-ischemic and hemorrhagic
      lesions. The authors give a short up-to-date report, focusing mainly on the third
      mechanism, with reference to personal studies.

PMID- 7648572
TI  - Identification of the cerebrospinal compensatory mechanisms via computer
      controlled drainage of the cerebrospinal fluid.
AB  - The constant rate infusion test is still widely used for the diagnosis of
      hydrocephalus in children. The increased resistance to reabsorption of the
      cerebrospinal fluid (CSF) is considered the most important factor in the
      improvement seen after shunting. However, the classic infusion test has some
      disadvantages: the compensatory model is identified in the conditions of raised
      intracranial pressure, which may provoke some uncontrolled changes in cerebral
      blood volume in the mechanism of vasomotor response; also non-linear effects in
      reabsorption mechanisms may have a significant influence. The controlled drainage
      of CSF can be considered as a form of pressure-volume testing if the volume of
      the drained fluid is precisely measured. The main advantage of the method is the
      possibility of estimating unknown parameters in practically physiological
      conditions (with only slightly decreased pressure). This paper presents a new
      method for the identification of an electrical model of cerebrospinal volume
      compensation. The method has been described theoretically, verified on the
      simulator and introduced into clinical practice at the Medical Academy in Warsaw
      and the Children's Health Center in Miedzylesie.

PMID- 7648573
TI  - Congenital dermal sinus associated with an abscessed intramedullary epidermoid
      cyst in a child: case report and review of the literature.
AB  - A 16-month-old male infant presented with paraparesis and a high thoracic skin
      dimple. After myelography the child underwent complete surgical removal of the
      dermal sinus and of an abscessed tumor located within the cervicothoracic cord.
      Histological study showed that the lesion was an intramedullary epidermoid cyst.
      Only four descriptions have previously been published of dermal sinuses
      associated with intramedullary epidermoids, three of them complicated by
      intramedullary abscesses. This appears to be the first report in the current
      literature of the association of a dermal sinus and an infected intramedullary
      epidermoid occurring out of the confines of the lumbosacral region.

PMID- 7648575
TI  - Report of a case of congenital glioblastoma multiforme: an immunohistochemical
      study.
AB  - We report a rare case of congenital glioblastoma multiforme in a 13-day-old male
      neonate born at term who died from cardiocirculatory failure. The cerebral tumor
      was diagnosed in vivo by magnetic resonance imaging and confirmed histologically
      after autopsy. The histological and immunohistochemical features of this case
      were similar to those reported in the adult.

PMID- 7648574
TI  - Transient mutism following a posterior fossa approach to cerebellar tumors in
      children: a critical review of the literature.
AB  - Transient mutism has been known as a rare complication following a posterior
      fossa approach to cerebellar tumors and its cause has not been clearly
      elucidated. The cerebellar mutism is not accompanied by cranial nerve deficits
      and disorders of consciousness. Since 1985 only 23 cases of mutism following
      removal of a cerebellar tumor in children have been reported in the literature.
      Two additional cases have been operated upon in our department. Extensive injury
      to the vermian and paravermian cerebellar area, involving the hemispheric cortex,
      cerebellar peduncles, fibers from the dentato-thalamocortical pathway, and
      dentate and interpositum nuclei may be the most important anatomical substrate of
      mutism. The mechanism of such transient mutism seems to be a complex of two or
      more factors (vascular disturbances due to manipulation or retraction of the
      cerebellar region around the IV ventricle and emotional factors). On the basis of
      these 25 cases the major features of the cerebellar mutism are discussed.

PMID- 7648576
TI  - Carboxymethylation of inulin.
AB  - Inulin was carboxymethylated in aqueous alkaline medium with monochloroacetic
      acid as the reagent. The degree of substitution of the reaction product was
      determined by titration, LC analysis and 13C NMR spectroscopy.
      Carboxymethylinulin with a degree of substitution between 0.2 and 1 was obtained
      depending on the molar ratio of inulin-monochloroacetic acid. Increasing the
      concentration of the reaction mixture and lowering the reaction temperature
      resulted in higher selectivities towards carboxymethylinulin. Determination of
      the molecular weight distribution was performed by GPC and by multi-angle laser
      light scattering. Carboxymethylation caused little or no degradation of the chain
      length of the starting material.

PMID- 7648577
TI  - An assay for the transferase activity of glycogen debranching enzyme.

PMID- 7648578
TI  - Enzymatic transformation of de-O-acetyl-lanatoside C into digoxin.

PMID- 7648579
TI  - A facile synthesis of 2-O-(alpha-D-mannopyranosyl)-alpha-D-mannopyranosides.

PMID- 7648580
TI  - Structural characterization of the pectic polysaccharide, rhamnogalacturonan-II.
AB  - An octasaccharide was released from sycamore cell wall rhamnogalacturonan-II (RG
      II) by selective acid hydrolysis of the glycosidic linkages of apiosyl residues
      and purified to homogeneity by gel-permeation and high-performance anion-exchange
      chromatographies. The octasaccharide 1 contains a terminal nonreducing beta-L
      arabinofuranosyl residue linked to position 2 of the alpha-L-rhamnopyranosyl
      residue of the aceric acid-containing heptasaccharide 2 that had been previously
      isolated from RG-II [M.W. Spellman et al. Carbohydr. Res., 122 (1983) 131-153].
      Heptasaccharide 2 and octasaccharide 1 were found to be mono- or di-O-acetylated.
      The O-acetyl groups were located, by ESMSMS, on the terminal nonreducing 2-O
      methyl-alpha-L-fucosyl residue and/or on the 2-linked beta-L-aceryl acid residue.
      Octasaccharide 1 and heptasaccharide 2 have the following structures: [structure:
      see text]

PMID- 7648581
TI  - Substrate specificity of small-intestinal lactase: study of the steric effects
      and hydrogen bonds involved in enzyme-substrate interaction.
AB  - Milk lactose is hydrolysed to D-galactose and D-glucose in the small intestine of
      mammals by the lactase-phlorizin hydrolase complex (LPH, EC 3.2.1.23-62). Lactase
      activity has broad substrate selectivity and several glycosides are substrates.
      Recently, using the monodeoxy derivatives of methyl beta-lactoside (1), we have
      shown the importance of each hydroxyl group in the substrate molecule concerning
      the interaction with the enzyme. Now we have studied the corresponding O-methyl
      derivatives, as well as some of the halo derivatives of 1. We have found that the
      enzyme presents steric restrictions to the recognition of substrates modified in
      the galactose moiety. In contrast, the binding site for the aglycon part of the
      substrate is looser. On the other hand, we have previously shown that HO-3' and
      HO-6 were important for the recognition of the substrate by the enzyme. Now we
      have found that the corresponding fluorine derivatives are not, or very poorly,
      recognized. This suggests that the HO-3' and HO-6 participate, as donors, in
      hydrogen bonds in the interaction with the enzyme.

PMID- 7648582
TI  - 1H- and 13C-NMR characterization of the digalactosylmannopentaose liberated from
      legume seed galactomannan by beta-mannanase action.
AB  - Incubation of Locust bean gum with an Aspergillus niger beta-D-mannanase released
      a wide variety of galactomannan oligomers. A single heptasaccharide,
      digalactosylmannopentaose, was obtained from fractionation of the mixture by size
      exclusion chromatography. The purity and chemical composition of the sample was
      demonstrated using mass spectrometry, high performance anion-exchange
      chromatography and monosaccharide composition analysis. The primary structure of
      this heptasaccharide was unambiguously identified using 2D 1H and 13C homonuclear
      and heteronuclear NMR. A complete assignment of the 1H and 13C signals of this
      oligomer was achieved, producing an NMR dataset that will be of importance in the
      primary structure elucidation of larger and more complex galactomannan oligomers.

PMID- 7648583
TI  - Simulation of the 13C nuclear magnetic resonance spectra of trisaccharides using
      multiple linear regression analysis and neural networks.
AB  - Predictive models are developed for the 13C NMR chemical shifts of the carbon
      atoms comprising the central rings of 46 trisaccharide compounds. Thirty-nine
      trisaccharides are used as a training set for development of models using
      regression analysis and computational neural networks, and seven compounds are
      used as an external prediction set. The descriptors used in the models are
      developed directly from the molecular structures of the trisaccharides. Three
      different methods of descriptor selection are compared. The dependence of the
      models on the geometries of the trisaccharides is explored. The models developed
      with geometric descriptors are better than those developed without geometric
      descriptors, although the latter models are still of a comparable quality.
      Overall, the best model found is a neural network based on descriptors selected
      by multiple linear regression.

PMID- 7648584
TI  - Synthesis of disaccharide glycosyl donors suitable for introduction of the beta-D
      Gal p-(1-->3)-alpha-and-beta-D-Gal pNAc groups.
AB  - 2-(Trimethylsilyl)ethyl 2-azido-4,6-O-benzylidene-2-deoxy-beta-D-
      galactopyranoside (4) was glycosylated with phenyl 2,3,4,6-tetra-O-acetyl-1-thio
      beta-D-galactopyranoside to give 2-(trimethylsilyl)ethyl 2-azido-4,6-O
      benzylidene-2-deoxy-3-O-(2,3,4, 6-tetra-O-acetyl-beta-D-galactopyranosyl)-beta-D
      galactopyranoside (6) in 99% yield. Removal of the benzylidene group and
      acetylation gave the key intermediate 2-(trimethylsilyl)ethyl 4,6-di-O-acetyl-2
      azido-2-deoxy-3-O-(2,3,4, 6-tetra-O-acetyl-beta-D-galactopyranosyl)-beta-D
      galactopyranoside (7), which was transformed into methyl 4,6-di-O-acetyl-2-deoxy
      2-phthalimido-3-O-(2,3,4, 6-tetra-O-acetyl-beta-D-galactopyranosyl)-1-thio-beta-D
      galactopyranosid e (9) in two steps in an overall yield of 69%. Similarly, 7 was
      transformed in two steps into 4,6-di-O-acetyl-2-azido-2-deoxy-3-O-(2,3,4, 6-tetra
      O-acetyl-beta-D-galactopyranosyl)-alpha-D-galactopyranosyl bromide (11) in an
      over-all yield of 86%. Compounds 9 and 11 are suitable glycosyl donors for
      introduction of the beta-D-Gal p-(1-->3)-beta- and -alpha-D-Gal pNAc groups.

PMID- 7648585
TI  - Characterisation of 4-deoxy-beta-L-threo-hex-4-enopyranosyluronic acid attached
      to xylan in pine kraft pulp and pulping liquor by 1H and 13C NMR spectroscopy.
AB  - A new acidic sidegroup in xylans, from both kraft pulp and pulping liquor, was
      identified by NMR spectroscopy. Unmodified oligosaccharides from kraft pulp xylan
      were obtained by enzymatic hydrolysis with xylanase (Trichoderma reesei). The
      acidic oligosaccharides were separated from the natural forms on an anion
      exchange resin. The new acidic sidegroup was identified as 4-deoxy-beta-L-threo
      hex-4-enopyranosyluronic acid (hexenuronic acid) by 1H and 13C NMR spectroscopy.
      Hexenuronic acid is a beta-elimination product of 4-O-methylglucuronic acid and
      is formed during kraft pulping. HMBC and NOESY experiments showed that
      hexenuronic acid is attached beta-(1 --> 2) to xylose. The NOESY data further
      indicated that hexenuronic acid protrudes from the main xylan chain. The pKa
      values for hexenuronic acid (3.03) and 4-O-methylglucuronic acid (3.14) attached
      (1 --> 2) to xylose were determined from pH-dependent chemical shifts.

PMID- 7648586
TI  - Synthesis of the saccharide moiety of galactosylgloboside (SSEA-3) and its
      conjugation to bovine serum albumin and Sepharose.
AB  - The pentasaccharide glycoside corresponding to galactosylgloboside (SSEA-3), beta
      D-Gal p-(1-->3)-beta-D-Gal pNAc-(1-->3)-alpha-D-Gal p-(1-->4)-beta-D-Gal p-(1-
      >4)-beta-D-Glc p-1-OCH2CH2Si-(CH3)3 (4), was synthesized via glycosylation (87%)
      of 2-(trimethylsilyl)ethyl 2,3,6-tri-O-benzyl-4-O-[2,3,6-tri-O-benzyl-4-O-(2,4, 6
      tri-O-benzyl-alpha-D-galactopyranosyl)-beta-D-galactopyranosyl]-beta-D -
      glucopyranoside (2) with the glycosyl donor methyl 4,6-di-O-acetyl-2-deoxy-2
      phthalimido-3-O-(2,3,4, 6-tetra-O-acetyl-beta-D-galactopyranosyl)-1-thio-beta-D
      galactopyranosid e (1), followed by removal of protecting groups. Compound 4 was
      transformed into the spacer glycoside beta-D-Gal p(1-->3)-beta-D-Gal pNAc-(1-->3)
      alpha-D-Gal p-(1-->4)-beta-D-Gal p-(1-->4)-beta-D-Glc p-1-SCH2CH2COOH (10), which
      was coupled to bovine serum albumin (BSA), and Sepharose beads, to give the
      corresponding neoglycoprotein (11, 6 mol of saccharide/mol of BSA), and
      glycosylated Sepharose (12, 2.7 mumol of saccharide/mL of sedimented beads),
      respectively. An improved synthesis of a protected globotetraoside beta-D-Gal
      pNAc-(1-->3)-alpha-D-Gal p-(1-->4)-beta-D-Gal p-(1-->4)-beta-D-Glc p-1
      OCH2CH2SiMe3 is also reported.

PMID- 7648587
TI  - Venography with carbon dioxide as a contrast agent.
AB  - PURPOSE: The purpose of this study was to evaluate the feasibility, safety, and
      potential role of carbon dioxide (CO2) as a contrast agent for venography.
      METHODS: Consecutive patients with contraindications to iodinated contrast agents
      or with unsatisfactory iodinated contrast studies underwent CO2 digital
      subtraction venography. The images were rated by three experienced angiographers.
      Image quality and complications were assessed. RESULTS: Over a 14-month period,
      66 vein segments were studied in 21 patients. There was good correlation between
      experienced angiographers on CO2 image quality (Ri = 0.80) and good agreement on
      diagnosis (k = 0.62). In 91% of the vein segments evaluated with C02 there was
      interobserver agreement on the diagnosis. Upper extremity veins were adequately
      imaged with CO2 alone in all (6/6) patients with contraindications to iodinated
      contrast. Following suboptimal iodinated contrast studies in six patients, CO2
      produced significantly better quality upper extremity central vein images (p <
      0.05). Pain following injection into peripheral veins was the only CO2-related
      complication. Inferior vena cava (IVC) filters were successfully deployed with
      CO2 alone in 78% (7/9) of patients; two required iodinated contrast. CONCLUSIONS:
      Based upon initial experience, CO2 venography can be recommended in patients with
      contraindications to iodinated contrast or unsatisfactory iodinated contrast
      studies.

PMID- 7648589
TI  - CO2 digital subtraction arteriography--advantages and current solutions for
      delivery and imaging.

PMID- 7648588
TI  - Carbon dioxide gas as a venous contrast agent to guide upper-arm insertion of
      central venous catheters.
AB  - PURPOSE: Evaluate in a prospective randomized study carbon dioxide (CO2) gas
      compared to iodinated contrast agent for image-guided placement of peripherally
      inserted central venous catheters (PICCs). METHODS: The upper-arm approach to the
      central vein was used for placement of PICCs in 74 patients requiring
      intermediate or long-term central venous access. Fluoroscopy was used to obtain
      venous access during peripheral injection of CO2 (n = 41) or low osmolar contrast
      material (Omnipaque 240 mgI/ml) (n = 33). RESULTS: Placement of PICCs was
      accomplished in 88% of the CO2 group and in 100% of the contrast group, with a
      mean venipuncture of two in both groups. Venous access was unsuccessful in five
      patients with CO2 due to a small vein, venous spasm, or technical failure. The
      mean and range of procedure times were 22.8 min (13-64 min) with CO2 and 23.2 min
      (12-60 min) with contrast material. The average and range of CO2 and nonionic
      contrast volumes injected during the procedure were 35.4 ml (5-300 ml) and 27.8
      ml (8-120 ml), respectively. Vital signs and oxygen saturation did not change
      significantly during or after injection of CO2. There was no incidence of adverse
      reaction following CO2 injection. CONCLUSION: CO2 gas is a useful contrast agent
      to guide upper-arm insertion of PICCs and may be a safe alternative in patients
      with renal insufficiency and/or allergy to iodinated contrast material.

PMID- 7648590
TI  - Anatomical observations on the renal veins and inferior vena cava at magnetic
      resonance angiography.
AB  - PURPOSE: To describe the renal vein and inferior vena cava (IVC) anatomy found at
      abdominal magnetic resonance (MR) angiography. METHODS: Gadolinium-enhanced,
      three-dimensional, time-of-flight MR angiograms of 150 patients were evaluated
      for the number and configuration of the renal veins, and the number,
      configuration, and dimensions of the IVC. Data were analyzed with the Student's t
      test. RESULTS: Retroaortic left renal veins were found in 7% of patients,
      circumaortic left renal veins in 5%, multiple right renal veins in 8%, and
      duplicated IVCs in 0.7%. The length of the infrarenal IVC averaged 94 mm in
      females and 110 mm in males (p < 0.00001). The length of the infrarenal IVC in
      patients with circumaortic and retroaortic left renal veins averaged 76 mm and 46
      mm, respectively. The mean maximal caval diameter was 23.5 +/- 4 mm. No megacavae
      (diameter if the mid-IVC > 28 mm) were identified. CONCLUSION: Variant renal vein
      and IVC anatomy can be identified at MR angiography.

PMID- 7648591
TI  - Juvenile nasopharyngeal angiofibroma: comparison of blood loss during removal in
      embolized group versus nonembolized group.
AB  - PURPOSE: This retrospective study was performed to assess the beneficial effect
      of preoperative embolization of juvenile nasopharyngeal angiofibromas (JNA) in
      terms of blood loss during surgery. METHODS: Intraoperative blood loss in a group
      of 7 patients who underwent 10 procedures for JNA without preoperative
      embolization was compared with the blood loss of 13 patients who underwent 16
      procedures after embolization of one or both external carotid arteries. RESULTS:
      Mean blood loss was 5380 ml in patients without embolization and 1037.5 ml in
      those with embolization. This difference was not statistically significant
      because of the high standard deviation in the nonembolized group. However, when
      data were analyzed by tumor stage, a significant difference was noted between the
      embolized and the nonembolized patients with high-grade tumors but not between
      those with low-grade tumors. CONCLUSION: Preoperative embolization of the
      branches of the external carotid appears to facilitate removal of high grade
      tumors. The benefit of embolization in those with low-grade tumors is less clear
      cut, probably because there is less vascularity in low-grade tumors and so
      removal is easier.

PMID- 7648592
TI  - Femoropopliteal artery recanalization: factors affecting clinical outcome of
      conventional and laser-assisted balloon angioplasty.
AB  - PURPOSE: The clinical efficacy of 44 successful conventional and laser-assisted
      recanalizations of the femoropopliteal artery was assessed in a noncomparative
      study by the life-table method. METHODS: Laser-assisted angioplasty using
      continuous laser and a sapphire probe was performed to achieve primary
      recanalization in femoral artery occlusions when conventional guidewire
      recanalization had already failed. Nineteen of the patients underwent a
      conventional recanalization (PTA; mean length of occlusion 4.4 +/- 4.1 cm), and
      25 underwent percutaneous laser-assisted angioplasty (PLA; mean length of
      occlusion 10.1 +/- 6.7 cm). RESULTS: There was no statistical relation between
      the preprocedure Fontaine classification and the success rate in the PTA cases (p
      = 0.25), whereas there was a statistical relation in the PLA cases: The success
      rate in patients preprocedurally classified as Fontaine II was better than in
      those classified as Fontaine III/IV (p = 0.05). After a 3-year follow-up the
      patency rate in the patients with the PTA recanalizations was 37% and that in
      those with the PLA procedure was 53%. This difference was not statistically
      significant (p = 0.47). CONCLUSION: It is concluded that the laser should remain
      an investigational device.

PMID- 7648593
TI  - Abscess formation in desmoid tumors of Gardner's syndrome and percutaneous
      drainage: a report of three cases.
AB  - PURPOSE: To describe abscess formation complications in desmoid tumors of
      patients with Gardner's syndrome and percutaneous drainage. METHODS: Three
      patients with Gardner's syndrome and intramesenteric desmoid tumors were
      diagnosed as having intratumor abscess formation. Percutaneous drainage was the
      initial method of treatment in each case. Two subsequently underwent surgical
      resection and one patient refused surgery and was lost to follow-up. RESULTS: In
      each case, percutaneous drainage and antibiotics resulted in clinical
      improvement. In two, fistulous communication with the small bowel could be
      demonstrated, presumed to be the cause of abscess formation. Surgical resection
      confirmed fistula communication to the small bowel. In the third patient, no
      fistula was seen and only percutaneous drainage was performed. CONCLUSION:
      Abdominal pain and fever in patients with Gardner's syndrome and desmoids is
      suggestive of abscess formation in these tumors. Percutaneous drainage is useful
      as initial management.

PMID- 7648594
TI  - Evaluation of venous injury caused by a percutaneous mechanical thrombolytic
      device.
AB  - PURPOSE: To study venous injury caused by a prototype percutaneous mechanical
      thrombolytic device. METHODS: Simulated thrombolysis was performed using the
      device, or the Fogarty balloon catheter (FBC) as control, in the infrarenal
      inferior vena cava (IVC) of 40 New Zealand white rabbits. Venous injury was
      evaluated by cavography, Evans blue dye staining, and histology at 0, 1, and 6
      weeks postprocedure. RESULTS: Both devices resulted in near complete endothelial
      denudation acutely. No differences in reendothelialization were noted at any time
      in the proximal and mid-IVC, but there was significantly greater
      reendothelialization in the distal IVC in the rabbits treated 6 weeks earlier
      with the device (p < or = 0.04). Additionally, the inner luminal diameter at
      necropsy for the 1-week rabbits treated with the FBC was significantly narrower
      in the distal and middle sections of the IVC when compared with the device (p <
      or = 0.02 for both segments). There was no luminal diameter difference at 0 or 6
      weeks. CONCLUSION: Based on a rabbit model, venous injury from the device was
      found to be similar to, and in the distal IVC less than, the routinely used FBC.

PMID- 7648595
TI  - Percutaneous transhepatic embolization as treatment for bleeding ileostomy
      varices.
AB  - We report two patients with bleeding stomal varices following total colectomy and
      ileostomy. The varices were demonstrated by superior mesenteric angiography and
      percutaneous transhepatic mesenteric venography; dilated ileal veins drained via
      the stomal varices into abdominal wall veins. Bleeding from the stomal varices
      was treated by transhepatic embolization. The first patient required three
      transhepatic embolizations after recurrent bleeding due to recanalization of the
      embolized ileal vein and the development of collaterals from the adjacent ileal
      veins over a one-year period. The second patient died of respiratory failure 1
      week after embolization. Neither patient developed mesenteric or stomal ischemia.

PMID- 7648596
TI  - Embolization of the hepatic falciform artery to prevent supraumbilical skin rash
      during transcatheter arterial chemoembolization for hepatocellular carcinoma.
AB  - A dilated hepatic falciform artery (HFA) arising from the left hepatic artery was
      demonstrated on arteriography prior to chemoembolization of an unresectable
      hepatocellular carcinoma (HCC) located predominantly in the left lobe of the
      liver. The HFA was occluded by microcoils to prevent a possible toxic
      supraumbilical skin rash following chemoembolization of the HCC via the left
      hepatic artery. There were no postprocedure complications. We consider this
      procedure useful for improving the safety of chemoembolization.

PMID- 7648597
TI  - Transarterial embolization of an extrahepatic portal vein aneurysm with
      arterioportal fistula.
AB  - We successfully performed transcatheter arterial embolization of an extrahepatic
      arterioportal fistula with a portal vein aneurysm. The fistula was considered
      secondary to cholecystectomy for cholecystolithiasis 5 years earlier. After
      occlusion of the fistula with platinum coils, the aneurysmal cavity thrombosed.

PMID- 7648598
TI  - Inadvertent arteriovenous stenting during transjugular intrahepatic portosystemic
      shunt procedure and the importance of hepatic artery perfusion.
AB  - Penetrating the hepatic artery during transjugular intrahepatic portosystemic
      shunt (TIPS) is a relatively frequent but almost always benign complication. We
      report a patient in whom the right hepatic artery, originating from the superior
      mesenteric artery, was inadvertently catheterized and stented. The arteriovenous
      fistula was treated with a detachable balloon positioned within the hepatic
      artery. A second TIPS was attempted and successfully created during the same
      session. The patient died of cardiac failure, attributed to rapid resolution of
      massive ascites after TIPS with circulatory overload. At autopsy, the liver
      distal to the arterial occlusion balloon was infarcted, illustrating the
      importance of hepatic artery perfusion on liver cirrhosis.

PMID- 7648599
TI  - Treatment of Budd-Chiari syndrome by metallic stent as a bridge to liver
      transplantation.
AB  - A 49-year-old male with Budd-Chiari syndrome complicated by liver cirrhosis and
      intractable ascites is reported. The left hepatic vein was stenosed by a short
      subocclusive ostial web; the right and medial hepatic veins were thrombosed. A
      spontaneous intrahepatic portosystemic shunt had developed between the left
      portal and left hepatic veins. After ineffective balloon angioplasty, the left
      hepatic venous outflow was restored by placement of a 10-mm-diameter Wallstent
      across the web via a femoral approach. The hepatic venous pressure dropped from
      29 to 12 mmHg. Rapid clinical improvement followed. The patient underwent liver
      transplantation 3 months later in stable condition.

PMID- 7648600
TI  - Percutaneous removal of a biliary stent after acute spontaneous duodenal
      perforation.
AB  - A 38-year-old woman was treated for malignant stricture by the endoscopic
      placement of a biliary endoprosthesis. She developed a large retroperitoneal
      biloma secondary to acute duodenal perforation by the stent. We describe the
      successful percutaneous retrieval of the biliary stent through a retroperitoneal
      approach which also permitted drainage of the biloma.

PMID- 7648601
TI  - Wire trapping in Rashkind's patent ductus arteriosus occluder: its etiology and
      how it may be avoided.
AB  - Release of the Rashkind ductus umbrella may be complicated in that the central
      wire of the delivery catheter may become trapped within the foam of the umbrella.
      This problem occurs only if the central retaining wire is advanced when trying to
      disengage the catheter and umbrella. We propose a simple solution to the problem:
      Retract the sleeve instead of advancing the retaining wire.

PMID- 7648602
TI  - Re: Rupture of the iliac artery during angioplasty after balloon embolectomy.

PMID- 7648603
TI  - Women's sensory experiences during cardiac catheterization.

PMID- 7648604
TI  - Genes and behavior as studied through gonadotropin-releasing hormone (GnRH)
      neurons: comparative and functional aspects.
AB  - 1. GnRH neurons migrate from olfactory placode into the developing basal
      forebrain in a manner which appears remarkably constant across all vertebrates
      studied, from fish to human beings. 2. Interruption of this migration can result
      in Kallmann's Syndrome. Absence of libido by individuals suffering from
      Kallmann's has allowed us to chart a causal route from a specific gene to a human
      social behavior.

PMID- 7648605
TI  - Amplitude and frequency modulation of pulsatile luteinizing hormone-releasing
      hormone release.
AB  - 1. A variety of neuroendocrine approaches has been used to characterize cellular
      mechanisms governing luteinizing hormone-releasing hormone (LHRH) pulse
      generation. We review recent in vivo microdialysis, in vitro superfusion, and in
      situ hybridization experiments in which we tested the hypothesis that the
      amplitude and frequency of LHRH pulses are subject to independent regulation via
      distinct and identifiable cellular pathways. 2. Augmentation of LHRH pulse
      amplitude is proposed as a central feature of preovulatory LHRH surges. Three
      mechanisms are described which may contribute to this increase in LHRH pulse
      amplitude: (a) increased LHRH gene expression, (b) augmentation of facilitatory
      neurotransmission, and (c) increased responsiveness of LHRH neurons to afferent
      synaptic signals. Neuropeptide Y (NPY) is examined as a prototypical afferent
      transmitter regulating the generation of LHRH surges through the latter two
      mechanisms. 3. Retardation of LHRH pulse generator frequency is postulated to
      mediate negative feedback actions of gonadal hormones. Evidence supporting this
      hypothesis is reviewed, including results of in vivo monitoring experiments in
      which LHRH pulse frequency, but not amplitude, is shown to be increased following
      castration. A role for noradrenergic neurons as intervening targets of gonadal
      hormone negative feedback actions is discussed. 4. Future directions for study of
      the LHRH pulse generator are suggested.

PMID- 7648607
TI  - Development of gonadotropin-releasing hormone (GnRH) neuron regulation in the
      female rat.
AB  - 1. After reaching its final destination the GnRH neuronal network develops under
      the influence of both excitatory and inhibitory inputs. 2. In the first 2 weeks
      of life, the immaturity of the GnRH neuronal system is reflected in sporadic
      unsynchronized bursts of the decapeptide, which determine the pattern of serum
      gonadotropin levels observed in female rats: high FSH levels and transient bursts
      of LH. The main inhibitory neuronal systems that operate in this period are the
      opioid and dopaminergic systems. A decrease in their inhibitory effectiveness may
      not be sufficient correctly to activate and synchronize the GnRH neuronal system.
      3. There is a concomitant increase in excitatory inputs, mainly noradrenaline,
      excitatory amino acids, and NPY, which increase the synthesis and release of GnRH
      at the beginning of the juvenile period and participate in the coupling of GnRH
      neural activity to the ongoing rhythmic activity of a hypothalamic circadian
      oscillator. 4. The morphological changes of GnRH neurons which take place during
      the third and fourth weeks of life, and which are probably related to increasing
      estradiol levels, reflects the increasing complexity of the GnRH neuronal
      network, which establishes synaptic contacts to enable the expression of
      pulsatility and of the positive feedback of estradiol, both necessary components
      for the occurrence of puberty.

PMID- 7648606
TI  - Control of luteinizing hormone-releasing hormone pulse generation in nonhuman
      primates.
AB  - 1. The pulsatile release of luteinizing hormone-releasing hormone (LHRH) is
      critical for reproductive function. However, the exact mechanism of LHRH pulse
      generation is unclear. The purpose of this article is to review the current
      knowledge on LHRH pulse generation and to discuss a series of studies in our
      laboratory. 2. Using push-pull perfusion in the stalk-median eminence of the
      rhesus monkey several important facts have been revealed. There is evidence
      indicating that LHRH neurons themselves have endogenous pulse-generating
      mechanisms but that the pulsatility of LHRH release is also modulated by input
      from neuropeptide Y (NPY) and norepinephrine (NE) neurons. The release of NPY and
      NE is pulsatile, with their pulses preceding or occurring simultaneously with
      LHRH pulses, and the neuroligands NPY and NE and their agonists stimulate LHRH
      pulses, while the antagonists of the ligands suppress LHRH pulses. 3. The
      pulsatile release of LHRH increases during the estrogen-induced LH surge as well
      as the progesterone-induced LH surge. These increases are partly due to the
      stimulatory effects of estrogen and progesterone on NPY neurons. 4. An increase
      in pulsatile LHRH release occurs at the onset of puberty. This pubertal increase
      in LHRH release appears to be due to the removal of tonic inhibition from gamma
      aminobutyric acid (GABA) neurons and a subsequent increase in the inputs of NPY
      and NE neurons to LHRH neurons. 5. There are indications that additional
      neuromodulators are involved in the control of the LHRH pulse generation and that
      glia may play a role in coordinating pulses of the release of LHRH and
      neuromodulators. 6. It is concluded that the mechanism generating LHRH pulses
      appears to comprise highly complex cellular elements in the hypothalamus. The
      study of neuronal and nonneuronal elements of LHRH pulse generation may serve as
      a model to study the oscillatory behavior of neurosecretion.

PMID- 7648608
TI  - Functional domains of the gonadotropin-releasing hormone receptor.
AB  - 1. The cloning of the mammalian gonadotropin-releasing hormone receptor sets the
      stage for rapid progress in understanding the structure of the receptor, its
      interaction with ligand, and its mechanisms of activation. 2. The receptor is a
      327 to 328-amino acid seven-transmembrane domain G protein-coupled receptor. 3.
      Recent site-direct mutagenesis studies have provided considerable insight into
      glycosylation of the receptor, the arrangement of the helices, and the ligand
      binding domains.

PMID- 7648610
TI  - Evolutionary aspects of gonadotropin-releasing hormone and its receptor.
AB  - 1. Gonadotropin-releasing hormone (GnRH) was originally isolated as a
      hypothalamic peptide hormone that regulates the reproductive system by
      stimulating the release of gonadotropins from the anterior pituitary. However,
      during evolution the peptide was subject to gene duplication and structural
      changes, and multiple molecular forms have evolved. 2. Eight variants of GnRH are
      known, and at least two different forms are expressed in species from all
      vertebrate classes: chicken GnRH II and a second, unique, GnRH isoform. 3. The
      peptide has been recruited during evolution for diverse regulatory functions: as
      a neurotransmitter in the central and sympathetic nervous systems, as a paracrine
      regulator in the gonads and placenta, and as an autocrine regulator in tumor
      cells. 4. Evidence suggests that in most species the early-evolved and highly
      conserved chicken GnRH II has a neurotransmitter function, while the second form,
      which varies across classes, has a physiologic role in regulating gonadotropin
      release. 5. We review here evolutionary aspects of the family of GnRH peptides
      and their receptors.

PMID- 7648609
TI  - Immortalized hypothalamic luteinizing hormone-releasing hormone (LHRH) neurons: a
      new tool for dissecting the molecular and cellular basis of LHRH physiology.
AB  - 1. Two LHRH neuronal cell lines were developed by targeted tumorigenesis of LHRH
      neurons in vivo. These cell lines (GN and GT-1 cells) represent a homogeneous
      population of neurons. GT-1 cells have been further subcloned to produce the GT1
      1, GT1-3, and GT1-7 cell lines. While considerable information is accumulating
      about GT-1 cells, very little is currently known about the characteristics and
      responses of GN cells. 2. By both morphological and biochemical criteria, GT-1
      cells are clearly neurons. All GT-1 cells immunostain for LHRH and the levels of
      prohormone, peptide intermediates, and LHRH in the cells and medium are
      relatively high. 3. GT-1 cells biosynthesize, process, and secrete LHRH.
      Processing of pro-LHRH appears to be very similar to that reported for LHRH
      neurons in vivo. At least four enzymes may be involved in processing the
      prohormone to LHRH. 4. LHRH neurons are unique among the neurons of the central
      nervous system because they arise from the olfactory placode and grow back into
      the preoptic-anterior hypothalamic region of the brain. Once these neurons reach
      this location, they send their axons to the median eminence. With respect to the
      immortalized neurons, GN cells were arrested during their transit to the brain.
      In contrast, GT-1 cells were able to migrate to the preoptic-anterior
      hypothalamic region but were unable correctly to target their axons to the median
      eminence. These problems in migration and targeting appear to be due to
      expression of the simian virus T-antigen. 5. While GT-1 cells are a homogeneous
      population of neurons, they are amenable to coculture with other types of cells.
      Coculture experiments currently under way should help not only to reveal some of
      the molecular and cellular cues that are important for neuronal migration and
      axonal targeting, but they should also highlight the nature of the cellular
      interactions which normally occur in situ. 6. GT-1 cells spontaneously secrete
      LHRH in a pulsatile manner. The interpulse interval for LHRH from these cells is
      almost identical to that reported for release of LH and LHRH in vivo. GT-1 cells
      are interconnected by both gap junctions and synapses. The coordination and
      synchronization of secretion from these cells could occur through these
      interconnections, by feedback from LHRH itself, and/or by several different
      compounds that are secreted by these cells. One such compound is nitric oxide. 7.
      GT-1 cells have Na+, K+, Ca2+, and Cl- channels.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7648611
TI  - Regulation of gonadotropin-releasing hormone (GnRH) gene expression in
      hypothalamic neuronal cells.
AB  - 1. Gonadotropin-releasing hormone (GnRH) is the hypothalamic releasing factor
      that controls pituitary gonadotropin subunit gene expression and indirectly
      gametogenesis and steroidogenesis from the gonad, which results in reproductive
      competence. 2. GnRH is synthesized in only about 1000 neurons in the hypothalamus
      and released in an episodic fashion down the median eminence to regulate
      gonadotropin biosynthesis. 3. Although much is known about the secretory dynamics
      of GnRH release, little is known about the pretranslational control of GnRH
      biosynthesis due to lack of appropriate model systems. The recent availability of
      immortalized neuronal cell lines that produce GnRH allows investigators for the
      first time to begin to dissect the factors that directly regulate GnRH gene
      expression. 4. This article reviews the current state of knowledge concerning the
      mechanisms that direct tissue-specific and peptide hormone control of GnRH
      biosynthesis.

PMID- 7648612
TI  - Dynamic alterations in luteinizing hormone-releasing hormone (LHRH) neuronal cell
      bodies and terminals of adult rats.
AB  - 1. The decapeptide lueteinizing hormone-releasing hormone (LHRH) is synthesized
      in neuronal cell bodies diffusely distributed across the basal forebrain and is
      secreted from neuronal terminals in the median eminence. Once secreted, LHRH
      enters the portal vessels and is then transported to the anterior pituitary,
      where it modulates the synthesis and secretion of gonadotropins, which are
      essential to gonadal function and reproduction. 2. Because of the difficulties
      encountered in studying these diffusely distributed neurons, we have developed
      strategies which combine immunocytochemistry and computer-assisted techniques to
      examine individual LHRH neuronal cell bodies, as well as the entire population of
      LHRH neurons from the diagonal band of Broca to the mammillary bodies. In
      addition, we have examined LHRH neuronal terminals in the median eminence using
      computer-assisted imaging techniques to examine individual terminals by electron
      microscopy or across all rostral-caudal regions of the median eminence by light
      microscopy. In our most recent studies using confocal microscopy, we have
      examined the relationships of LHRH terminals to glial processes. 3. These studies
      reveal a very dynamic system of LHRH neuronal cell bodies and terminals. The
      population of neurons in which LHRH can be detected varies as a function of time
      after gonadectomy, during the estrous cycle, and during the preovulatory surge of
      LH during the afternoon of proestrus. Dynamic changes are also observed in LHRH
      terminals in the median eminence as a function of time after gonadectomy and in
      specific rostral-caudal regions of the median eminence during the preovulatory
      surge of LH. Finally, confocal microscopy reveals that LHRH terminals are
      prevented from contacting the basal lamina of the brain by glial end-feet. 4. We
      are currently examining the hypothesis that these relationships change as a
      function of endocrine milieu and, therefore, participate in the modulation of
      LHRH secretion. Ongoing studies focus on defining the sites of action and synergy
      of multiple sources of regulation of LHRH secretion and their relative importance
      to ensuring reproductive success.

PMID- 7648613
TI  - The "steric blocking model," the "six-state model," and the ATPase activity of
      regulated actomyosin.
AB  - There has been a great deal of interest in the regulation of muscle contraction.
      Prior biochemical studies have demonstrated that the binding of regulated actin
      to S-1-ATP is unchanged at low Ca2+, even though the ATPase activity of regulated
      actomyosin is inhibited under these conditions. Prior structural studies using X
      ray diffraction techniques have suggested that the tropomyosin-troponin complex
      may move and inhibit the actomyosin interaction at low Ca2+ (i.e., steric
      blocking). In physiologic fiber experiments, "weak" binding crossbridges have
      been found to bind to the actin filament at low Ca2+, especially at low ionic
      strength, and other experiments have suggested that Pi release is not directly
      regulated by calcium. In biochemical studies in the absence of ATP, inhibition of
      the binding of strong binding states have been reported in both equilibrium and
      transient kinetic studies. The current work suggests that all of these
      observations can be explained in terms of a six-state model in which regulation
      affects one particular actomyosin state that contains both strongly bound ADP and
      Pi. This further implies that regulation affects both a kinetic transition as
      well as a weak binding constant.

PMID- 7648614
TI  - Determination of the kinetics of permeation of dimethyl sulfoxide in isolated
      corneas.
AB  - Corneal cryopreservation requires that endothelial cells remain viable and
      intercellular structure be preserved. High viability levels for cryopreserved
      endothelial cells have been achieved, but preserving intercellular structure,
      especially endothelial attachment to Descemet's membrane, has proved difficult.
      Cell detachment apparently is not caused by ice, suggesting osmotic or chemical
      mechanisms. Knowledge of the permeation kinetics of cryoprotectants (CPAs) into
      endothelial cells and stroma is essential for controlling osmotic and chemical
      activity and achieving adequate tissue permeation prior to cooling. Proton
      nuclear magnetic resonance (NMR) spectroscopy was used to assess the permeation
      of dimethyl sulfoxide (DMSO) into isolated rabbit corneas. Corneas with intact
      epithelia were exposed to isotonic medium or 2.0 mol/L DMSO for 60 min and
      subsequently transferred to 2.0 or 4.0 mol/L DMSO, respectively, at 22, 0, or -10
      degrees C. DMSO concentration in the cornea was measured vs time. The Kedem
      Katchalsky model was fitted to the data. Hydraulic permeability (m3/N.s) is 7.1 x
      10(-13) + 216%-11% at 22 degrees C, 8.2 x 10(-13) + 235%-21% at 0 degree C, and
      1.7 x 10(-14) + 19%-16% at -10 degrees C. The reflection coefficient is 1.0 + 2%
      1% at 22 degrees C and 0 degree C, and 0.9 +/- 5% at -10 degrees C. Solute
      mobility (cm/s) is 5.9 x 10(-6) + 6%-11% at 22 degrees C, 3.1 x 10(-6) + 12%-11%
      at 0 degree C, and 5.0 x 10(-8) cm/s + 59%-40% at -10 degrees C.

PMID- 7648615
TI  - In situ hybridization and immunohistochemistry of renal angiotensinogen in
      neonatal and adult rat kidneys.
AB  - Recent evidence suggests that a local renin-angiotensin system is operational in
      the kidney and that it mediates some of the actions of angiotensin II on renal
      tubules. In this study the ontogeny and renal distribution of the unique
      precursor to angiotensin II formation, angiotensinogen, was investigated in rats
      by use of immunohistochemistry, immuno-electron microscopy and non-isotopic
      hybridization histochemistry. At the light-microscopic level, intense staining
      for angiotensinogen was found in the proximal convoluted tubules of the cortex,
      with lighter staining in the straight proximal tubules of the outer stripe. The
      strongest immunostaining was found in the kidneys of neonatal rats, where
      glomerular mesangial cells and medullary vascular bundles were also
      immunopositive. The angiotensinogen content of the kidneys in late gestation
      embryos and neonates showed the presence of angiotensinogen by day E18 and a peak
      content in the neonate. Non-isotopic hybridization histochemistry with
      biotinylated oligodeoxynucleotide probes confirmed the presence of
      angiotensinogen mRNA expression in the proximal convoluted tubules of the renal
      cortex. Electron-microscopic immunohistochemistry showed staining of relatively
      few electron-dense structures close to the apical membrane of proximal convoluted
      tubule cells in the adult kidney. In the neonatal rat kidney, angiotensinogen
      immunostaining at the electron-microscopic level was found throughout the
      proximal tubule cells and was markedly stronger than that seen in adult kidney.
      The presence of angiotensinogen, from embryonic day 18, in the proximal tubules,
      mesangial cells and vasculature of the kidney suggests multiple potential sites
      of intrarenal angiotensin II generation with an ontogeny in late gestation.

PMID- 7648616
TI  - Regional brain glutamate transport in rats at normal and raised concentrations of
      circulating glutamate.
AB  - The permeability of the blood-brain barrier to glutamate was measured by
      quantitative autoradiography in brains of control rats (average plasma glutamate
      concentration of 95 microns) and rats infused with glutamate (average plasma
      glutamate concentration of 837 microns). Measurements of glutamate permeability
      were initiated by the injection of [14C]glutamate and stopped at 1 min to avoid
      the accumulation of [14C]glutamate metabolites. Glutamate entered the brain at a
      slow rate, with an average permeability-surface area product of 7 microliters.min
      g-1, except in those areas known to have fenestrated capillaries. Glutamate
      accumulated in the choroid plexus of ventricles, but did not seem to enter the
      cerebrospinal fluid in detectable amounts regardless of the circulating
      concentration. Glutamate accumulated in circumventricular organs, such as the
      median eminence, where the radioactivity was localized without detectable spread.
      Infusion of glutamate to create high plasma concentrations did not result in
      greater spread of [14C]glutamate beyond the immediate vicinity of the
      circumventricular organs.

PMID- 7648617
TI  - Effects of fibroblasts of different origin on long term maintenance of
      xenotransplanted human epidermal keratinocytes in immunodeficient mice.
AB  - We examined effects of fibroblasts of different origin on long-term maintenance
      of xenotransplanted human epidermal keratinocytes. A suspension of cultured
      epidermal cells, originating from adult human trunk skin, was injected into
      double mutant immunodeficient (BALB/c nu/scid) mice subcutaneously, with or
      without cultured fibroblastic cells of different origin. At one week after
      transplantation, the epidermal cells generated epidermoid cysts consisting of
      human epidermis-like tissue. When the epidermal cells were injected alone or
      together with fibroblastic cells derived from human bone marrow, muscle fascia,
      or murine dermis, organized epidermoid cysts regressed within 6 weeks. In
      contrast, when the epidermal cells were injected together with human dermal
      fibroblasts, generated epidermoid cysts were maintained in vivo for more than 24
      weeks. Histological examination showed that the reorganized epidermis, after
      injection of both epidermal keratinocytes and dermal fibroblasts, retained normal
      structures of the original epidermis during 6 to 24 weeks after transplantation.
      The results indicate that human dermal fibroblasts facilitate the long-term
      maintenance of the reorganized epidermis after xenotransplantation of cultured
      human epidermal keratinocytes by supporting self renewal of the human epidermal
      tissue in vivo.

PMID- 7648618
TI  - The monoclonal antibody GB 42--a useful marker for the differentiation of
      myofibroblasts.
AB  - The expression patterns of a variety of cytoskeletal antigens were studied in
      normal human tissues (placenta, umbilical cord, myometrium, colon, mammary gland,
      testis, skeletal muscle, myocardium) as well as in abnormal human tissues (palmar
      fibromatosis, fibrocystic disease of the mammary gland, mammary carcinoma). The
      immunohistochemical binding patterns of the monoclonal antibody GB 42 were
      compared to those of commercial antibodies directed against vimentin, desmin,
      smooth muscle myosin, pan actin, alpha-smooth muscle actin and gamma-smooth
      muscle actin. Methods applied comprised immunohistochemistry on cryostat sections
      and paraffin sections. Immunogold immunocytochemistry was performed on Lowicryl
      sections. The patterns of GB 42-binding were confirmed biochemically by SDS-PAGE
      and Western-blotting, and quantitative amino acid analysis. Our data suggest that
      the monoclonal antibody GB 42 recognizes an actin isoform which is identical to,
      or closely related to, gamma-smooth muscle actin. Unlike the commercially
      available antibody against gamma-smooth muscle actin, GB 42 does not cross-react
      with alpha-skeletal or alpha-cardiac actins. The GB 42-antigen is expressed in
      smooth muscle cells, myoepithelial cells and in later stages of differentiation
      of myofibroblasts, in all the tissues investigated. Throughout the development of
      smooth muscle cells and myofibroblasts, the appearance of the GB 42-antigen
      occurs after the expression of vimentin, desmin and alpha-smooth muscle actin,
      but prior to the expression of smooth muscle myosin. GB 42 is a reliable marker
      for higher stages of differentiation of smooth muscle cells and myofibroblasts.

PMID- 7648619
TI  - Differential binding patterns of three antibodies (VOBM1, VOBM2, and VOM2) in the
      rat vomeronasal organ and accessory olfactory bulb.
AB  - Immunohistochemical properties of monoclonal antibodies raised against the rat
      vomeronasal epithelium were examined in adult rats. Three monoclonal antibodies,
      VOBM1, VOBM2, and VOM2, reacted specifically to the luminal surface of the
      sensory epithelium of the vomeronasal organ. In addition, the reactivities of
      VOBM1 and VOBM2 were detected in the vomeronasal nerve layer and the glomerular
      layer of the accessory olfactory bulb. Electron-microscopic study revealed
      differential patterns of the immunoreactivity of the three antibodies to the
      microvilli of vomeronasal sensory epithelium. VOBM1 immunoreactivity was found on
      the microvilli of the supporting cells, whereas VOBM2 immunoreactivity was found
      on those of the sensory cells. VOM2 immunoreactivity was observed on the
      microvilli of both the sensory and supporting cells. These results suggest that
      the three antibodies recognize different antigens on the vomeronasal sensory
      epithelium. In particular, VOBM2 antibody appears to react to an antigen specific
      to the microvilli of the vomeronasal sensory cells.

PMID- 7648620
TI  - Evolution and ultrastructure of the bovine spermatogonia precursor cell line.
AB  - The spermatogonial stem cell line in prepubertal and adult bovine testis was
      studied by electron microscopy and protein gene product 9.5 immunohistochemistry.
      Three successive spermatogonia precursor cell configurations were observed. Small
      basal stem cells were found to possess a spherical shape and nuclei with two to
      three nucleoli. They were observed in prepubertal testes (25 and 30 weeks) and in
      low numbers during all the stages of the seminiferous epithelial cycle in the
      adult. Aggregated spermatogonia precursor cells are the dominating germ cell type
      in the 25-week-old and 30-week-old calf. In the adult seminiferous epithelium,
      they cause expansion of the basal tubular compartment as they form dense groups
      containing up to 15 cells. These groups are observed concomitantly with cycling A
      spermatogonia and preleptotenes at the beginning of spermatocytogenesis. At the
      end of A-spermatogonia propagation, the aggregated spermatogonia precursor cells
      separate and intermingle with cycling A-spermatogonia. The spermatogonia
      precursor cells can later be found together with I-spermatogonia as members of an
      interconnected cellular network of medium-sized cells. When the I-spermatogonia
      divide to form the smaller B-spermatogonia, the precursor cells, which stay
      connected with the cycling spermatogonial population, pass through a growth
      phase. They can now be considered as committed spermatogonia precursor cells and
      are continuously being transformed into A1-spermatogonia to start a new round of
      spermatocytogenesis. Ultrastructurally, all members of the precursor cell line
      are similar. However, a number of features have been found to show a quantitative
      increase (endoplasmic reticulum, mitochondria) or to exhibit a rising degree of
      complexity (nucleolus) during the progression from basal stem cells to committed
      spermatogonia precursor cells.

PMID- 7648621
TI  - Immunohistochemical localization of the calcium/calmodulin-dependent protein
      phosphatase, calcineurin, in the mouse testis: its unique accumulation in
      spermatid nuclei.
AB  - Immunohistochemical localization of a calmodulin-dependent protein phosphatase,
      calcineurin, was studied in the mouse testis in relation to previous observations
      showing that calmodulin is unusually rich in spermatogenic stages from mid
      pachytene spermatocytes to elongating spermatids. The antibodies raised against
      calcineurin from scallop testis reacted with subunit B, but not subunit A, of
      calcineurin isoforms from mouse brain and testis. Indirect immunofluorescence
      using these antibodies on the mouse testis revealed positive reactions only in
      the nuclei of round or elongating spermatids: calcineurin started to accumulate
      in nuclei from the acrosomal cap phase, peaked at the initial stage of nuclear
      elongation, and decreased thereafter. There was almost no signal in the
      cytoplasm; spermatogenic cells at other stages, including spermatogonia,
      spermatocytes, mature sperm, and other somatic cells in the seminiferous tubules
      were totally negative. Immuno-electron microscopy gave the same result, on the
      basis of measuring the density of immunogold particles. These results suggest a
      role for calcineurin in remodeling of the nuclear chromatin in metamorphosing
      spermatids.

PMID- 7648622
TI  - A new combination of methods for the localization, identification, and three
      dimensional reconstruction of the sensory endings of articular afferents
      characterized by electrophysiology.
AB  - A combination of methods is described to identify and reconstruct corpuscular and
      non-corpuscular sensory endings of group II and group III nerve fibers following
      functional examination by electrophysiology. Afferent units activated by
      electrical stimulation of the medial articular nerve of the cat's knee were
      analyzed by single fiber recordings and characterized by their responsiveness to
      mechanical stimuli. The receptive fields of the units were closely demarcated by
      fine needles when the responses elicited by insertion of the needles were being
      recorded. After fixation, the tissue around the demarcated field was dissected
      and histologically processed. Series of semithin sections were cut from the
      embedded tissue blocks containing the receptive fields. Corpuscular endings of
      group II fibers and peripheral myelinated group III nerve fibers, presumably
      corresponding to the characterized units, were identified by light microscopy of
      semithin sections and localized within the demarcated area. Non-corpuscular
      endings were identified by electron microscopy of ultrathin sections cut in
      alternation with, or after re-embedding of, semithin sections. Morphometric
      analysis of ultrathin section series allowed the measurement of parameters such
      as the mean axon diameter and the organelle content of the sensory endings. The
      methods described are appropriate for collecting data that correlate the
      structural and functional characteristics of sensory endings in deep tissues.

PMID- 7648623
TI  - Detection of FMRFamide-like immunoreactivities in the sea scallop Placopecten
      magellanicus by immunohistochemistry and western blot analysis.
AB  - FMRFamide-like immunoreactivity was detected histochemically in the sea scallop
      Placopecten magellanicus. Most immunoreactivity was concentrated in the cerebral,
      pedal, and parietovisceral ganglia, particularly in the cortical cell bodies and
      in their fibers which extend into the central neuropile. Whole-mount
      immunofluorescence studies were used to localize concentrations of immunoreactive
      cells on the dorsal and ventral surfaces of each ganglion. Immunoreactivity was
      also detected in nerves emanating from the ganglia. Strong immunoreactivity was
      localized in peripheral organs, including the gut and gills of juvenile and adult
      scallops. Weak immunoreactivity was detected in the gonads, heart, and adductor
      muscle of the adults. A broad FMRFamide-like immunoreactive band of 2.5-8.2 kDa
      was detected by Western blotting of acetone extracts of the parietovisceral
      ganglia. In the presence of protease inhibitors, two FMRFamide-like
      immunoreactive bands (7.2-8.2 kDa and > 17 kDa) were obtained. Neither of these
      bands comigrated with the FMRFamide standard. It is concluded that peptides of
      the FMRFamide family are probably regulators of numerous central and peripheral
      functions in P. magellanicus.

PMID- 7648624
TI  - In vivo restitution of airway epithelium.
AB  - Epithelial shedding occurs in health and, extensively, in inflammatory airway
      diseases. This study describes deepithelialisation, reepithelialisation and
      associated events in guinea-pig trachea after shedding-like epithelial denudation
      in vivo. Mechanical deepithelialisation of an 800-microns wide tracheal zone was
      carried out using an orotracheal steel probe without bleeding or damage to the
      basement membrane. Reepithelialisation was studied by scanning- and transmission
      electron microscopy and light microscopy. Nerve fibres were examined by
      immunostaining. Cell proliferation was analysed by [3H]-thymidine
      autoradiography. Immediately after epithelial removal secretory and ciliated (and
      presumably basal) epithelial cells at the wound margin dedifferentiated,
      flattened and migrated rapidly (2-3 microns/min) over the denuded basement
      membrane. Within 8-15 h a new, flattened epithelium covered the entire
      deepithelialised zone. At 30 h a tight epithelial barrier was established and
      after 5 days the epithelium was fully redifferentiated. After completed migration
      an increased mitotic activity occurred in the epithelium and in
      fibroblasts/smooth muscle beneath the restitution zone. Reinnervating
      intraepithelial calcitonin gene-related peptide-containing nerve fibres appeared
      within 30 h. We conclude that (1) reproducible shedding-like denudation, without
      bleeding or damage to the basement membrane, can be produced in vivo; (2)
      secretory and ciliated cells participate in reepithelialisation by
      dedifferentiation and migration; (3) the initial migration is very fast in vivo;
      (4) shedding-like denudation may cause strong secretory and exudative responses
      as well as proliferation of epithelium, and fibroblasts/smooth muscle. Rapid
      restitution of airway epithelium may depend on contributions from the
      microcirculation and innervation.

PMID- 7648625
TI  - Transforming growth factor beta 1-hyaluronic acid interaction.
AB  - Chick embryo skin fibroblasts release transforming growth factor beta 1 that is
      able to modulate glycosaminoglycan synthesis and secretion. When incubated with
      individual classes of glycosaminoglycans, the factor's modulatory activity was
      altered. To determine whether direct interactions between transforming growth
      factor beta 1 and glycosaminoglycans occur, we have assessed the activity of the
      growth factor after pre-incubation with single classes of glycosaminoglycans by
      assaying its inhibitory effect upon the proliferative response of thymocytes
      stimulated with interleukin-1. Untreated transforming growth factor beta 1
      suppressed the proliferative response of thymocytes to interleukin-1, as did
      transforming growth factor beta 1 pre-incubated with sulphated
      glycosaminoglycans. By contrast, transforming growth factor beta 1 lost its
      inhibitory capacity when preincubated with high molecular weight hyaluronic acid.
      Digestion of transforming growth factor beta 1-hyaluronic acid complex with
      hyaluronidase released active transforming growth factor beta 1. Trypsin degraded
      transforming growth factor beta 1 alone, but did not degrade the transforming
      growth factor beta 1-hyaluronic acid complex. These results suggest that
      hyaluronic acid interacts with transforming growth factor beta 1, thus protecting
      the factor from tryptic degradation and may be a means of concentrating growth
      factor activity.

PMID- 7648626
TI  - Topography and distribution of nerve fibers in the posterior longitudinal
      ligament of the rat: an immunocytochemical and electron-microscopical study.
AB  - The distribution and immunocytochemical characterization of nerve fibers and
      their terminals in the posterior longitudinal ligament of the rat lumbar
      vertebral column was studied in whole-mount preparations and serial semithin and
      ultrathin sections. Differences in the localization, distribution pattern and
      density of peptidergic and catecholaminergic nerve fibers were found in the
      vertebral and intervertebral regions of the posterior longitudinal ligament. For
      immunocytochemistry, free floating specimens were incubated with primary
      antibodies against protein gene product 9.5, substance P, calcitonin gene-related
      peptide, dopamine-beta-hydroxylase, vasoactive intestinal polypeptide and
      neuropeptide Y together with the avidin-biotin-peroxidase method. In whole-mount
      preparations, the neural marker protein gene product 9.5 is immunostained in all
      unmyelinated nerve fibers in the posterior longitudinal ligament, thus giving a
      panoramic view of the nerve fiber plexus. The most striking nerve fiber plexus is
      localized in the intervertebral region. In this region, the posterior
      longitudinal ligament is rich in capillaries that form a dense plexus within its
      ventral part and extend to the outer layer of the annulus fibrosus. The
      peptidergic and catecholaminergic innervation of the posterior longitudinal
      ligament is discussed in the context of pain syndromes related to the vertebral
      column and degenerative lumbar spine diseases.

PMID- 7648627
TI  - Distribution of SchistoFLRFamide-like immunoreactivity in the adult ventral
      nervous system of the locust, Schistocerca gregaria.
AB  - SchistoFLRFamide (PDVDHVFLRF-NH2) is one of the major endogenous neuropeptides of
      the FMRFamide family found in the nervous system of the locust, Schistocerca
      gregaria. To gain insights into the potential physiological roles of this
      neuropeptide we have examined the distribution of SchistoFLRFamide-like
      immunoreactivity in the ventral nervous system of adult locusts by use of a newly
      developed N-terminally specific antibody. SchistoFLRFamide-like immunoreactivity
      in the ventral nerve cord is found in a subgroup of the neurones that are
      immunoreactive to an antiserum raised against bovine pancreatic polypeptide
      (BPP). In the suboesophageal ganglion three groups of cells stain, including one
      pair of large posterior ventral cells. These cells are the same size, in the same
      location in the ganglion and have the same branching pattern as a pair of BPP
      immunoreactive cells known to innervate the heart and retrocerebral glandular
      complex of the locust. In the thoracic and abdominal ganglia two and three sets
      of cells, respectively, stain with both the SchistoFLRFamide and BPP antisera. In
      the abdominal ganglia the immunoreactive cells project via the median nerves to
      the intensely immunoreactive neurohaemal organs.

PMID- 7648628
TI  - Cranial meninges of goldfish: age-related changes in morphology of meningeal
      cells and accumulation of surfactant-like multilamellar bodies.
AB  - In the optic tectum of goldfish, the outer, middle and inner layers of the
      endomeninx were evident in animals ranging in age from 1 month to several years.
      The outer layer in young animals consisted of closely overlapping cells with
      intertwined processes, whereas in the older animals it contained large
      extracellular spaces. The intermediate layer cells were always arranged in a
      single continuous layer, but in young animals they overlapped extensively with
      one another toward their edges whereas in the oldest animals they became
      extremely flat and non-overlapping. The inner layer included an outer tier of
      cells with their bases adhering to the intermediate layer, and an inner tier of
      cells detached from both the intermediate layer and the basal lamina overlying
      the brain parenchyma. Inner layer cells contained many large vacuoles that were
      in continuity with the extracellular space. With age, the extracellular space and
      the vacuolar system expanded, and the inner layer evolved into a meshwork of
      attenuated cytoplasmic processes embedded in the granular extracellular matrix.
      Another age-related feature was the accumulation adjacent to the basal lamina of
      uniform disc-shaped membranous structures, resembling multilamellar bodies of
      lung surfactant. These "disc bodies" were apparently generated by the coalescence
      of vesicles formed at the surface of the inner layer cells, possibly as a by
      product of protein secretion by these cells.

PMID- 7648629
TI  - The bridge-partitioning complex of germ-cell intercellular bridges in the testis
      of the golden hamster.
AB  - The bridge-partitioning complex present in pre-existing intercellular bridges of
      dividing spermatogonia in the juvenile golden hamster testis was studied by
      electron microscopy. There is a close temporal adjustment in the appearance of
      this structure to those stages of mitosis during which the cells are without a
      nuclear membrane, i.e., the bridge-partitioning complex is formed at the
      transition between prophase and prometaphase and gradually disappears during
      telophase. In addition, in a certain form of degenerative dividing germ cells,
      which completely lack a bridge-partitioning complex in pre-existing intercellular
      bridges, condensed chromatin not surrounded by a nuclear membrane occasionally
      projects through these open bridges and thus may well change over to a
      neighboring cell of the same clone. These results strongly indicate an essential
      barrier function of the bridge-partitioning complex. It temporarily prevents
      intraclonal exchange of nuclear material during those stages of mitosis where a
      nuclear membrane is lacking and, thus, maintains genetic integrity of male germ
      cells during synchronous divisions.

PMID- 7648630
TI  - Ultrastructural distribution of endogenous immunoglobulin-G in human term
      amniochorion.
AB  - Maternal immunoglobulin-G (IgG) is known to be transported across the placental
      syncytiotrophoblast during the period when the human fetus is incapable of
      manufacturing these defensive molecules. In this study we investigated the
      possible role of the amniochorion, that surrounds the amniotic cavity in which
      the fetus lies, in the transfer of immunoglobulin. Endogenous IgG was localised
      in the amniochorion by confocal immunofluorescence microscopy and by
      ultrastructural labelling of ultrathin frozen tissue sections using the protein A
      gold technique. Immunoreactivity was identified in the extracellular matrix
      tissues and necrotic amniotic epithelial cells. Healthy amniotic epithelial cells
      and cytotrophoblast cells of the chorion laeve were devoid of endogenous IgG.
      These results suggest a possible non-specific paracellular transport pathway
      between cytotrophoblast cells, which may conceivably contribute to the
      acquisition of passive immunity by the fetus, and offer a rational explanation
      for the presence of small quantities of maternal IgG in the amniotic fluid.

PMID- 7648631
TI  - NPY- and CGRP-like immunoreactive nerve fibers in the testis and mesorchium of
      the toad (Bufo arenarum).
AB  - The presence and distribution of peptidergic nerve fibers were studied in the
      testis and mesorchium of the toad by means of immunohistochemistry. Cryostat
      sections of the testis and whole-mount preparations of mesorchia were
      immunostained with antisera to calcitonin gene-related peptide (CGRP) and
      neuropeptide tyrosine (NPY). After leaving the mesorchium CGRP-immunoreactive
      (IR) fibers were seen predominantly running in between the seminiferous tubules.
      In addition, a small population of CGRP-IR nerve fibers formed thin plexuses
      around blood vessels. Conversely, NPY-like immunoreactivity predominated in nerve
      fibers that formed dense plexuses around vessels both in the mesorchium and
      testis. Additionally, some single NPY-IR nerve fibers could be seen in both
      structures studied. The functional significance of these peptidergic systems in
      the testis of the toad remains to be analyzed.

PMID- 7648632
TI  - Compensatory responses and development of the nodose ganglion following ablation
      of placodal precursors in the embryonic chick (Gallus domesticus).
AB  - The nodose ganglion is the distal cranial ganglion of the vagus nerve which
      provides sensory innervation to the heart and other viscera. In this study,
      removal of the neuronal precursors which normally populate the right nodose
      ganglion was accomplished by ablating the right nodose placode in stage 9 chick
      embryos. Subsequent histological evaluation showed that in 54% of lesioned
      embryos surviving to day 6, the right ganglion was absent. Most embryos surviving
      to day 12, however, had identifiable right ganglia. In day 12 embryos, the right
      ganglion which developed was abnormal, with ganglion volume and ganglion cell
      diameter reduced by 50% and 20%, respectively, compared to control ganglia. To
      investigate the source of the neuron population in the regenerated ganglion, we
      combined nodose placode ablation with bilateral replacement of chick with quail
      "cardiac" neural crest (from mid-otic placode to somite 3). These cells normally
      provide only non-neuronal cells to the nodose ganglion, but produce neurons in
      other regions. At day 9, quail-derived neurons were identified in the right
      nodose ganglia of these chimeras, indicating that cardiac neural crest cells can
      generate neurons in the ganglion when placode-derived neurons are absent or
      reduced in number. On the other hand, we found that "sympathetic" neural crest
      (from somites 10 to 20) does not support ganglion development, suggesting that
      only neural crest cells normally present in the ganglion participate in
      reconstituting its neuronal population. Our previous work has shown that right
      nodose placode ablation produces abnormal cardiac function, which mimics a life
      threatening human heart condition known as long QT syndrome. The present results
      suggest that the presence of neural crest-derived neurons in the developing right
      nodose ganglion may contribute to the functional abnormality in long QT syndrome.

PMID- 7648633
TI  - Adhesion of intermediate filaments and lipid droplets in adrenal cells studied by
      field emission scanning electron microscopy.
AB  - High-resolution field emission scanning electron microscopy was used to study the
      organisation of intermediate filaments around lipid droplets and their binding to
      these droplets, in primary culture of bovine adrenal cells. Whole-mount
      preparations of intermediate filaments and bound lipid droplets were prepared
      from cells grown on Formvar-coated grids and processed by freeze-drying.
      Intermediate filaments were seen as an interconnected network enveloping the
      entire droplet. The bound filaments appear to be directly adherent to the surface
      of the droplet and hence take on its curved contour. The binding of the filaments
      to the droplets was determined by means of tilting. This study provides a new
      approach to investigate the cytoskeleton and its associated structures with high
      resolution three-dimensional images.

PMID- 7648634
TI  - [An investigation on acute flaccid paralysis (AFP) cases in some provinces with
      high risk of poliomyelitis of China].
AB  - In the mid Jun, 1994, a study team organized by MOPH investigated AFP cases in 10
      provinces with high prevalence of poliomyelitis (polio). Twenty prefectures and
      ten counties were selected randomly from each of 10 provinces and relevant
      prefectures. The team identified 681 AFP cases under 15 years old from 45
      hospitals at prefecture level and 13 hospitals at country level based on hospital
      records from cases occurred during 1991-1994. AFP, Polio, Non-polio AFP and GBS
      (Guillian-Barre Syndrome) cases aged from 0-14 years scattered around 101
      counties (cities) among target population and their average incidences by year
      were 1.04, 0.48, 0.57 and 0.31 (per 10(5) respectively. Noticingly, the incidence
      of polio had reduced significantly since 1991, and its proportion among AFP was
      also reducing from first place yearly since 1991. In addition, over 95% of the
      polio cases were concentrated in the 4 year olds which indicated that the target
      population for surveillance and prevention should mainly be focusing on 0-4 year
      olds. As the incidence of non-polio AFP has been used as a current sensitive
      index of surveillance system, we noticed that the incidence rates had been
      significantly different from various regions. According to the analytic data, we
      recommend that "Rate of non-polio AFP in children 0-14 years of age greater than
      1/10(5)" might be a better and more sensitive index for surveillance program in
      China.

PMID- 7648635
TI  - [Study on the contamination of Ruditapes philippinarum by HAV in Jiaozhou Bay and
      its counter-measures].
AB  - Six surveillance spots were set up in Jiaozhou Bay to examine the contamination
      of Ruditapes Philippinarum (R. P) by HAV. Specimens were collected regularly
      every month. Seventy-five specimens were collected in July 1991-Aug 1992. The
      precursor RNA of HAV was detected by methods of PCR, RNA dot-blot hybridization
      and HAV isolation. It showed that R. P. had been contaminated by HAV in some
      areas of the bay at times, but the virus was in a state of inactivity.
      Epidemiologic investigation in the same period proved that R. P. was not the
      direct cause of HA epidemic in Qingdao. However, the domestic sewage is directly
      drained into the Jiao zhou Bay so the control of the city sewage drainage system
      must be enforced and health education serve for people in taking sea food and
      drink should be strengthened.

PMID- 7648637
TI  - [An epidemiological investigation of eperythrozoon infection in human and
      animals. A Collaborative Research Group on Eperythrozoonosis].
AB  - This paper reported an epidemiological investigation on human and animal
      Eperythrozoons infection in five districts from three provinces in China. The
      results showed that Eperythrozoon infection appeaned in human as well as in
      swines, sheep and cats. Due to geographical variations, the infectious rates
      showed significantly difference both in human and in animals. The infection rate
      in human was not associated with sex, age or occupation. Some questions related
      to the epidemiology of Eperythrozoonosis were discussed in this article.

PMID- 7648636
TI  - [A prospective epidemiological investigation on the effect of China-mode
      attenuated live vaccine against hepatitis A in the population of Liu Zhou].
AB  - An 24-month prospective epidemiological investigation on the results of China
      mode Hepatitis A attenuated live vaccine against hepatitis A by random group
      sampling was carried out. The incidence of case group was 15.91/10(5) (5/31421),
      the incidence of control group was 95.92/10(5) (30/ 31277) which showed a
      significant difference. In case group 2081 persons who missed vaccination, there
      was one person developed hepatitis A, making the incidence 48.05/10(5). In
      control group 760 persons were vaccinated by mistake and there was no case
      developed in this sub-population. There were 644 cases of hepatitis A in the
      external control group, the incidence was 90.14/10(5). Data showed that there was
      no significant difference among external control group, control group and persons
      from case group who missed vaccination. Comparing the data from case group and
      from the above 3 groups, the protective rates were 82.35%, 83.41% and 66.89%.
      respectively. When conparing the data from persons who had been mistakenly
      vaccinated in control group, there was no significant difference being noticed.

PMID- 7648638
TI  - [Epidemiologic investigation on the occurrence of brucellosis in a rabbitry
      family].
AB  - This article reports epidemiologic investigations on the occurrence of
      brucellosis in a rabbitry family in Laoting County, Hebei Province. Three persons
      of this family were all examined. The results of examinations by serology,
      bacteriology, clinical observations, and epidemiological history showed that: Two
      of the three cases were suffering from Brucellosis. Domestic animals in this
      house and the domestic animals and feeders in the neighborhood were investigated
      by serology and bacteriology. The results demonstrated that the source of
      infection was the dog fed by the family and infected by Brucella sheep biotype.

PMID- 7648639
TI  - [A study on the epidemiologic features of sporadic legionellosis in children].
AB  - 317 hospitalized children and 86 healthy children were collected between April 4,
      1991 and April 3, 1992 were detected for IgM antibodies to Legionella using ELISA
      with sonicated and EDTA antigens of 9 species (15 serogroups). The total positive
      rate was 13.25% (42/317) in hospitalized children and 2.33% (2/86) in healthy
      children. Legionellosis was diagnosed in 35 cases, of which 25 (11.68%) with
      respiratory illnesses, 5 (5/15) with kidney diseases or blood diseases and 1
      (1.45%) with other disease. The proportion of legionellosis was 11.04% (35/317).
      Of the 15 antigens tested, significant antibodies levels were detected in 11.
      Tatlock micdadei constituted 47.62% (20/42). Lp(1-6)23.81% (10/42) and L.
      bozemane 14.29% (6/42). There was higher proportion of legionellosis in elder
      children and in summer time.

PMID- 7648640
TI  - [Investigation of nosocomial infection among 2126 operative patients].
AB  - In an investigation on 2126 operative patients in a hospital in 1992, 227 were
      found to have nosocomial infection with 241 person-times. The nosocomial
      infection rate was 10.68% and the case infection rate was 11.34%. They were
      higher than nonoperative nosocomial infection rate and case infection rates were
      4.85% and 4.98%, respectively. The main sites of infection were postoperative
      cuts, in lower respiratory tract and urinary tract. These three parts held 82.12%
      of the sites of infection.

PMID- 7648641
TI  - [A prospective study of perioperative antibiotic prophylaxis in reducing the rate
      of nosocomial infection among patients with intracranial tumors].
AB  - This paper analysed 525 intracranial neoplastic patients who were hospitalized
      from July, 1992 to June, 1993. The patients were randomly divided into control
      and experiment groups. In the experiment group, patients who received one kind of
      antibiotic during perioperation had a nosocomial infection rate of 6.29%
      (11/175), while the patients in the control group where antibiotics were
      routinely used as usual had a rate of 17.43% (61/350). There was a significant
      difference between the control (8.00%) and experiment group (2.29%) in terms of
      the intracranial infection incidence. Perioperative antibiotic prophylaxis showed
      great influence on the expenditure of antibiotics and duration of hospitalization
      in the patients with intracranial neoplastic tumors.

PMID- 7648642
TI  - [Contrast study on the cases of peptic ulcer evident bleeding induced causes].
AB  - To suppose violent movement, slow overfatique, irritation of emotions, over
      eating, empty stomach, eating rotten food, over drinking, use of non-steroid anti
      inflammatory drug and non-use of H2-receptor blocking agents as the evident
      bleeding induced causes of peptic ulcer, comparison between 139 cases with peptic
      ulcer evident bleeding (PUEB) and 139 cases with peptic ulcer non-bleeding and
      contrast analysis of the cases with PUEB themselves was conducted. Results showed
      that the ratio of PUEB with those exposed in various causes were bigger than that
      of the contrast. PUEB themselves were obviously associated with violent movement
      (P < 0.01), slow overfatigue (P < 0.05), over-eating (P < 0.05), over-drinking (P
      < 0.025) and non-use of H2-receptor blocking agents (P < 0.005) in different
      degrees. The result of self-contrast of the patients with PUEB agrees with that
      of pair-matched analysis.

PMID- 7648643
TI  - [Hepatitis virus infection and bone marrow transplantation].
AB  - Hepatitis virus infection is a special problem in China and the role of Hepatitis
      virus infection in allogeneic bone marrow transplantation (BMT) is not well
      defined. In this study, 106 BMT patients were included for analysis of the role
      of virus infection in allo-BMT. Seven and 65 of 106 patients were found to have
      HBV infection and HCV infection, respectively. Neither HBV infection and HCV
      infection interfered with the engraftment of bone marrow cells nor increased the
      rate of AGVHD, CGVHD, VOID. Neither HBV infection nor HCV infection prohibited
      allo-BMT. But Hepatitis virus infection can cause mild to moderate liver
      dysfunction, even death because of acute liver function failure, active
      prevention and treatment of hepatitis virus infection remains necessary. In this
      respect, rh-interferon is useful.

PMID- 7648644
TI  - [Progress in the study on the transmission routes of epidemic hemorrhagic fever].

PMID- 7648645
TI  - [Current status of the study on haemophilus influenzae].

PMID- 7648646
TI  - Nifedipine and mortality. Grave defects in the dossier.

PMID- 7648647
TI  - Nifedipine in ischemic heart disease.

PMID- 7648648
TI  - Calcium antagonists in coronary artery disease and hypertension. Time for
      reevaluation?

PMID- 7648649
TI  - Infiltrates of activated mast cells at the site of coronary atheromatous erosion
      or rupture in myocardial infarction.

PMID- 7648650
TI  - Infiltrates of activated mast cells at the site of coronary atheromatous erosion
      or rupture in myocardial infarction.
AB  - BACKGROUND: Erosion and rupture of coronary atheromas are the events preceding
      the vast majority of acute coronary syndromes. The shoulder regions of atheromas,
      the sites at which erosion or rupture is most likely to occur, are the sites at
      which mast cells accumulate. These cells are filled with neutral proteases
      capable of triggering extracellular matrix degradation via activation of matrix
      metalloproteinases. To obtain more direct evidence for the participation of mast
      cells in the acute coronary syndromes, we quantified the numbers of mast cells at
      eroded or ruptured sites of coronary atheromas in patients who died of myocardial
      infarction. METHODS AND RESULTS: In specimens of coronary arteries from 20
      patients who had died of acute myocardial infarction, the site of atheromatous
      erosion or rupture was identified. The specimens were stained with monoclonal
      antibodies against the two major proteases of mast cells, tryptase and chymase,
      and against macrophages, T lymphocytes, and smooth muscle cells. At the immediate
      site of erosion or rupture, mast cells amounted to 6% of all nucleated cells, in
      the adjacent atheromatous area to 1%, and in the unaffected intimal area to 0.1%.
      The proportions of these mast cells that were activated, ie, had been stimulated
      to degranulate and release some of their tryptase and chymase contents, were 86%
      at the site of erosion or rupture, 63% in the adjacent atheromatous area, and 27%
      in the unaffected intima. At the site of erosion or rupture, the numbers of
      macrophages and T lymphocytes were also increased, but the number of smooth
      muscle cells was decreased. CONCLUSIONS: The accumulation of activated mast cells
      (200-fold more than in the unaffected coronary intima) at the site of
      atheromatous erosion or rupture suggests that in thrombotic coronary occlusion
      the role played by mast cells is significant.

PMID- 7648651
TI  - Genetic variation on chromosome 1 associated with variation in body fat
      distribution in men.
AB  - BACKGROUND: Interindividual variation in fat deposition in swine is determined by
      loci on porcine chromosome 4, which are contained in a region that is syntenic
      with part of the long arm of human chromosome 1. We hypothesized that genomic
      variation of chromosome 1q would be associated with variation in the ratio of
      waist-to-hip circumference in male North American Hutterites, a genetic isolate
      characterized by significant relatedness and sharing of environmental factors.
      METHODS AND RESULTS: In 316 male Hutterites, we tested for phenotype-genotype
      association of two DNA polymorphisms on chromosome 1q and the ratio of waist-to
      hip circumference. We included control loci on 10 other chromosomes in the
      multivariate model. We observed that DNA variation on chromosome 1q was
      significantly associated with variation in the ratio of waist-to-hip
      circumference in men (P = .0029). CONCLUSIONS: The association of DNA variation
      chromosome 1q with the ratio of waist-to-hip circumference in male Hutterites
      suggests that there are important structural elements in this genomic region that
      have a functional impact on body fat distribution.

PMID- 7648652
TI  - Long-term cigarette smoking impairs endothelium-dependent coronary arterial
      vasodilator function.
AB  - BACKGROUND: Smoking is a primary risk factor for coronary and peripheral vascular
      disease. Because the endothelium is a principal target for the effects of risk
      factors early in the pathogenesis of atherosclerosis, we investigated whether
      long-term smoking is associated with impaired endothelial vasodilator function of
      epicardial conductance vessels regardless of the presence or absence of
      atherosclerotic lesions. METHODS AND RESULTS: Using quantitative coronary
      angiography, we measured epicardial artery diameter at baseline, after maximal
      increases in coronary blood flow that caused flow-mediated dilation (which is
      strictly endothelium dependent), and after intracoronary injection of
      nitroglycerin (an endothelium-independent dilator) in 96 patients. Endothelium
      dependent, flow-mediated dilation was significantly (P < .0001) blunted in
      smokers (n = 46) compared with non-smokers (n = 50). The ratio of flow-dependent
      dilation to nitroglycerin-induced dilation was significantly (P < .001) lower in
      smokers (0.34 +/- 0.32) compared with nonsmokers (0.59 +/- 0.23), indicating that
      the blunted dilator response to increased blood flow was out of proportion to the
      mildly impaired dilator response to nitroglycerin in smokers. In the presence of
      angiographically visible atherosclerosis, flow-dependent dilation was essentially
      absent (3.0 +/- 6.5%) in smokers. Multivariate analysis revealed that luminal
      irregularities by angiography (P < .0001) and smoking (P < .001) were the only
      variables to be independently associated with a reduced flow-dependent dilator
      response of epicardial arteries. Intracoronary ultrasound demonstrated that flow
      dependent dilation progressively decreased with increasing atherosclerotic plaque
      load (r = -.82, P < .0001; n = 24). However, over the entire range of wall
      thickening, segments from smokers exhibited a significantly (P < .01) impaired
      flow-dependent dilator response compared with those of nonsmokers. CONCLUSIONS:
      Long-term cigarette smoking is associated with impaired endothelium-dependent
      coronary vasodilation regardless of the presence or absence of coronary
      atherosclerotic lesions.

PMID- 7648653
TI  - Effect of infarct artery patency on prognosis after acute myocardial infarction.
      The Survival and Ventricular Enlargement Investigators.
AB  - BACKGROUND: In patients with acute myocardial infarction (MI), early restoration
      of patency of the infarct-related artery (IRA) leads to preservation of left
      ventricular function and improved clinical outcome. However, there is evidence
      that the benefits associated with a patent IRA are out of proportion to the
      observed improvement in ventricular function and may result not only from salvage
      of ischemic myocardium but also from the opening of the IRA beyond a narrow
      postinfarct time window. The objectives of this study were (1) to assess the
      effect of IRA patency on outcome of patients after acute MI with left ventricular
      dysfunction while controlling for differences in left ventricular ejection
      fraction and the extent of coronary disease and (2) to determine the effect of
      angiotensin-converting enzyme (ACE) inhibitor therapy on patients with patent as
      well as occluded infarct arteries. METHODS AND RESULTS: The Survival and
      Ventricular Enlargement (SAVE) study consisted of 2231 patients with a documented
      MI and a left ventricular ejection fraction < or = 40%. They were randomized to
      the ACE inhibitor captopril (50 mg TID) or placebo 3 to 16 days after MI and were
      followed for an average of 3.5 years. Left ventricular ejection fraction,
      measured with radionuclide left ventriculography, was repeated at the end of the
      follow-up period. The 946 patients in whom the patency of the IRA was established
      before randomization form the basis of this study. At cardiac catheterization
      averaging 4.2 days after infarction, 30.7% of patients had an initially occluded
      IRA. After revascularization, 162 of the 946 patients (17.1%) were left with an
      occluded IRA at the time of randomization. The 162 patients with persistently
      occluded IRAs and 784 with patent IRAs had similar clinical baseline
      characteristics, but those with occluded arteries had a slightly lower ejection
      fraction than the 784 patients with patent infarct arteries (30% versus 32%, P =
      .01). Cox proportional-hazards analyses showed that the independent predictors of
      all-cause mortality were hypertension (relative risk [RR] 1.94, P < .001), number
      of diseased coronary arteries (RR 1.68, P < .001), occluded IRA (RR 1.49, P =
      .039), ejection fraction (RR 1.36, P < .001), age (RR 1.10, P = .030), and use of
      beta-adrenergic receptor blocking agents (RR 0.60, P = .007). Independent
      predictors of a composite end point consisting of cardiovascular mortality,
      morbidity, or reduction of ejection fraction of > or = 9 units were occluded IRA
      (odds ratio [OR] 1.73, P = .002), hypertension (OR 1.71, P < .001), number of
      diseased vessels (OR 1.38, P < .001), ejection fraction (OR 1.18, P = .003), use
      of beta-adrenergic receptor blocking agents (OR 0.67, P = .007), and
      randomization to captopril (OR 0.70, P = .009). CONCLUSIONS: IRA patency within
      16 days after MI predicts a favorable clinical outcome, independent of the number
      of obstructed coronary arteries or of left ventricular function. The beneficial
      effect of ACE inhibition is independent of patency status of the IRA. These
      findings support the need for additional, prospective clinical trials of late
      reperfusion in MI patients.

PMID- 7648654
TI  - Benefit of thrombolytic therapy is sustained throughout five years and is related
      to TIMI perfusion grade 3 but not grade 2 flow at discharge. The European
      Cooperative Study Group.
AB  - BACKGROUND: Long-term follow-up in patients treated with thrombolysis for acute
      myocardial infarction thus far has been reported in a few studies only, and no
      long-term follow-up is available for patients who underwent additional
      percutaneous transluminal coronary angioplasty (PTCA). This report describes 5
      year survival as collected in patients who received placebo, recombinant tissue
      plasminogen activator (rTPA), or rTPA with additional immediate PTCA in two
      European Cooperative Study Group trials. Determinants for long-term survival were
      assessed in 1043 patients discharged alive. METHODS AND RESULTS: Five-year follow
      up information on mortality was collected. Hospital mortality was lower after
      rTPA than placebo (2.5% versus 5.7%, P = .04) and higher after rTPA with
      immediate PTCA compared with rTPA without additional intervention (6.0% versus
      2.2%, P = .07). Of the 1043 hospital survivors, data were available for 923
      patients, of whom 109 died. In the placebo group, mortality after hospital
      discharge was 10.7% versus 11.0% in the comparative rTPA group. The patients
      treated with rTPA and immediate PTCA had a mortality rate of 10.5% versus 8.9% in
      the rTPA group without PTCA (all P = NS). Significant determinants of mortality
      in multivariate proportional hazards analysis were enzymatic infarct size,
      indicators of residual left ventricular function, number of diseased vessels and
      TIMI perfusion grade at discharge. Patients with TIMI grade 2 flow had mortality
      rates similar to those with TIMI flow grades 0 and 1, while prognosis was better
      in patients with TIMI flow grade 3. CONCLUSIONS: The initial in-hospital benefit
      of thrombolysis with intravenous rTPA is maintained throughout 5 years, with no
      early or late beneficial effect of systematic immediate PTCA. Enzymatic infarct
      size, left ventricular function, and extent of coronary artery disease are
      predictors for long-term survival. TIMI perfusion grade 2 at discharge should be
      considered as an inadequate result of therapy.

PMID- 7648655
TI  - Regional heterogeneity of human myocardial infarcts demonstrated by contrast
      enhanced MRI. Potential mechanisms.
AB  - BACKGROUND: Myocardial reperfusion is pivotal to the prognosis of patients with
      acute myocardial infarction. In these patients, coronary flow is generally
      assessed by angiography and tissue perfusion by tracer scintigraphy. This study
      was designed to examine whether magnetic resonance imaging (MRI) provides
      information on myocardial perfusion and damage beyond that supplied by
      angiography and thallium scintigraphy after acute myocardial infarction. METHODS
      AND RESULTS: Twenty-two patients with recent myocardial infarction had ECG,
      echocardiography, coronary angiography, and fast contrast-enhanced MRI. Twelve
      patients also had exercise thallium scintigraphy. Time-intensity curves obtained
      from infarcted and noninfarcted regions were correlated with coronary anatomy and
      left ventricular function. Two perfusion patterns were observed in infarcted
      regions by comparison with the normal myocardial pattern. All patients but 1 had
      persistent myocardial hyperenhancement within the infarcted region up to 10
      minutes after contrast. In 10 patients, this hyperenhanced region surrounded a
      subendocardial area of decreased signal at the center of the infarcted region
      associated with coronary occlusion at angiography, Q waves on ECG, and greater
      regional dysfunction by echocardiography. Moreover, the extent and location of
      the MRI abnormalities correlated well with the extent and location of the fixed
      single-photon emission computed tomography thallium defects. CONCLUSIONS: Large
      human infarcts, associated with prolonged obstruction of the infarct-related
      artery, are characterized by central dark zones surrounded by hyperenhanced
      regions on MRI. Conversely, reperfused infarcts with less regional dysfunction
      have uniform signal hyperenhancement. The MRI hyperenhanced segment correlates
      well with the fixed scintigraphic defect in patients with acute myocardial
      infarction.

PMID- 7648656
TI  - Influence of preexistent donor coronary artery disease on the progression of
      transplant vasculopathy. An intravascular ultrasound study.
AB  - BACKGROUND: Transplant vasculopathy (TxCAD) limits longterm survival of allograft
      recipients. The possibility that preexistent donor coronary disease (PEDD) might
      accelerate this process is of concern. The serial progression of sites with and
      without PEDD as assessed by intravascular ultrasonic imaging is explored in this
      study. METHODS AND RESULTS: Thirty patients with baseline intravascular imaging
      within 3 weeks of cardiac transplantation who had at least one annual follow-up
      study were included in this study. Vessel luminal area (LA), total area (TA),
      intimal index (II = TA - LA/TA), mean intimal thickness (MIT), and Stanford
      classification were expressed for each image site and for each patient at each
      study. Progression of sites and of patients with and without PEDD on the baseline
      study was compared. Patients with PEDD (n = 9) still had significantly more
      intimal disease than those without PEDD (n = 21) at the first follow-up study
      (MIT = 0.35 +/- 0.13 versus 0.13 +/- 0.11 mm; II = 0.29 +/- 0.11 versus 0.11 +/-
      0.1; class = 3.7 +/- 0.5 versus 2.2 +/- 0.94; P < .001 for all comparisons).
      However, the increase in intimal thickness during the 1- year interval was not
      significantly different between the two groups. In 4 patients in whom both types
      of sites were present, no difference in progression was found. Data were similar
      for patients and sites studied over > 1 year. CONCLUSIONS: PEDD does not
      accelerate the progression of TxCAD within the first few years after cardiac
      transplantation. The pathophysiology of TxCAD is most likely immune mediated and
      does not seem to be accelerated by native coronary artery disease.

PMID- 7648657
TI  - Influence of sex on the short-term outcome of elderly patients with a first acute
      myocardial infarction.
AB  - BACKGROUND: Sex seems to affect the course of acute myocardial infarction (AMI)
      in the general population. Although the epidemiological importance of female sex
      among patients with AMI is more important from the sixth decade of life, little
      is known about the impact of sex on the outcome of AMI in the elderly. METHODS
      AND RESULTS: To determine the differences between sexes in the outcome of AMI in
      the elderly, we compared the clinical history and evolution of 204 consecutive
      patients (99 men, 105 women) > or = 75 years of age admitted with a first AMI.
      Women had a higher prevalence (P < .01) of hypertension (60% versus 32%) and
      diabetes (41% versus 18%), whereas men were more frequently smokers (41% versus
      4%, P < .0001); these factors were associated with higher rates of congestive
      heart failure. Women showed lower ejection fractions and higher rates of
      congestive heart failure (odds ratio [OR], 2.32; 95% CI, 1.32 to 4.12) and shock
      (OR, 2.78; 95% CI, 1.29 to 6.40). Mortality rate was higher in women (40% versus
      23%, P = .01; OR, 2.29; 95% CI, 1.26 to 4.26); however, sex was excluded as an
      independent predictor of in-hospital mortality in every regression model tested
      (OR, 0.75; 95% CI, 0.25 to 2.21). CONCLUSIONS: After a first AMI, elderly women
      experience a more complicated hospital course than men. The increase in mortality
      risk seems to be related to the impact of cardiovascular risk factors on left
      ventricular function more than to sex itself.

PMID- 7648658
TI  - Association of coronary disease with segment-specific intimal-medial thickening
      of the extracranial carotid artery.
AB  - BACKGROUND: Several investigators have evaluated relations between risk factors
      and intimal-medial thickness (IMT) of the extracranial carotid arteries and
      between IMT and clinical cardiovascular disease. Different indexes of IMT have
      been used as referents. We compared the strength of association of various IMT
      measurements with coronary artery disease as measured at coronary angiography.
      METHODS AND RESULTS: We quantified the mean of the IMT for 12 sites of the
      extracranial carotid arteries (common carotid, bifurcation, internal carotid,
      near and far walls, and left and right sides [mean aggregate]) as well as for
      various combinations of sites (eg, segment-specific means, far walls only,
      maximum of any site) in 270 patients with or free of coronary artery disease.
      Models including age and all the indexes of IMT identified the mean aggregate as
      the only variable independently associated with the status of coronary
      atherosclerosis for the group as a whole. Next most strongly correlated was the
      mean common plus bifurcation. When classification algorithms were tested for
      ability to correctly classify case patients and control subjects, the mean
      bifurcation, mean common plus bifurcation, and mean aggregate were most strongly
      related to case-control status; however, the predictive power of the mean common
      was also strong. CONCLUSIONS: These data support use of the mean aggregate
      extracranial carotid IMT for correlation with the status of coronary
      atherosclerosis; however, the data also support use of the mean common plus
      bifurcation, since there is little increase in predictive power of the mean
      aggregate over this index. Use of the common carotid alone is also justifiable
      and may be preferable for certain analyses.

PMID- 7648659
TI  - Albumin microbubble echo-contrast material as an enhancer for ultrasound
      accelerated thrombolysis.
AB  - BACKGROUND: Recent findings suggest that acoustic cavitation is responsible for
      acceleration of thrombolysis by ultrasound (US) energy. It is known that albumin
      microbubbles lower the threshold of acoustic cavitation production. METHODS AND
      RESULTS: The present study was designed to determine whether the presence of
      albumin microbubbles used for echo-contrast material (Albunex) can further
      accelerate fibrinolysis of US. Artificial thrombus was produced by Chandler's
      loop method with blood extracted from a healthy subject. Urokinase (UK, 1200
      IU/mL) was added to the artificial thrombi placed in test tubes. Each thrombus
      was exposed to US (170 kHz) at a distance of 1.2 cm for a total of 60 seconds at
      an intensity of 0.5 W/cm2 at intervals of 2 seconds on and 4 seconds off. Echo
      contrast material (0.6 x 10(6) microspheres per mL) or 5% albumin (for control)
      was circulated near the thrombus at a rate of 1 mL/min during the US exposure.
      Fibrinolysis was later determined by percentage of weight loss of thrombus after
      60 minutes of incubation (n = 15). Fibrinolysis with UK alone was 26.6 +/- 4.8%.
      Fibrinolysis with UK+US treatment was 33.3 +/- 5.8%. Further increase of
      fibrinolysis to 51.3 +/- 7.7% occurred in the presence of Albunex
      (UK+US+Albunex). Statistical differences were obtained between all these groups
      (ANOVA). CONCLUSIONS: The presence of the echo-contrast agent induced further
      acceleration of thrombolysis by US energy. It is suggested that this diagnostic
      echo-contrast material can be used as an alternative therapeutic US drug enhancer
      for thrombolysis.

PMID- 7648660
TI  - Magnetic resonance imaging assessment of the severity of mitral regurgitation.
      Comparison with invasive techniques.
AB  - BACKGROUND: In the patient with mitral regurgitation who is being considered for
      valvular surgery, cardiac catheterization is usually performed to quantify the
      severity of regurgitation and to determine its influence on left ventricular
      volumes and systolic function. Magnetic resonance imaging (MRI) potentially
      provides a rapid, noninvasive method of acquiring these data. Thus, this study
      was done to determine whether MRI can reliably measure the magnitude of mitral
      regurgitation and evaluate the effect of regurgitation on left ventricular
      volumes and systolic function. METHODS AND RESULTS: Twenty-three subjects (14
      women and 9 men 15 to 72 years of age) with (n = 17) or without (n = 6) mitral
      regurgitation underwent MRI scanning followed immediately by cardiac
      catheterization. The presence (or absence) of valvular regurgitation was
      determined, and left ventricular volumes and regurgitant fraction were quantified
      during each procedure. There was excellent correlation between invasive and MRI
      assessments of left ventricular end-diastolic (r = .95) and end-systolic (r =
      .95) volumes and regurgitant fraction (r = .96). All MRI examinations were
      completed in < 28 minutes. CONCLUSIONS: In the patient with mitral regurgitation,
      MRI compares favorably with cardiac catheterization for assessment of the
      magnitude of regurgitation and its influence on left ventricular volumes and
      systolic function.

PMID- 7648661
TI  - Radiofrequency catheter ablation of sustained ventricular tachycardia in
      idiopathic dilated cardiomyopathy.
AB  - BACKGROUND: The feasibility of radiofrequency (RF) catheter ablation for the
      treatment of sustained ventricular tachycardia (VT) in patients with coronary
      artery disease and remote myocardial infarction has recently been demonstrated.
      At present, therapeutic options for VT in patients with idiopathic dilated
      cardiomyopathy (DCM) include antiarrhythmic drugs and implantable
      cardioverter/defibrillators (ICD). The purpose of the present study was to
      investigate the feasibility of RF catheter ablation in patients with idiopathic
      DCM who could not be adequately treated by conventional treatment modalities
      because of incessant or frequent, recurrent VT. METHODS AND RESULTS: RF current
      application for ablation of 9 VTs (mean cycle length, 402 +/- 78 ms) was
      attempted in 8 patients with idiopathic DCM (4 men, 4 women; mean age, 54 +/- 6
      years; mean left ventricular ejection fraction, 30 +/- 9%). Inclusion criteria
      for ablation were incessant VT (n = 4) or frequent, recurrent VT reproducibly
      inducible with programmed electrical stimulation (n = 5). Three patients had
      suffered aborted sudden cardiac death, and 2 had experienced syncope. Two
      patients were artificially ventilated and catecholamine dependent for hemodynamic
      reasons at the time of attempted ablation. Potential target sites for RF current
      application were identified by detailed endocardial mapping during sinus rhythm,
      activation and entrainment mapping during VT, and pace mapping. After 7 +/- 5 RF
      pulses (range, 2 to 18 pulses; median, 6 pulses) applied with 32 +/- 7 W for 39
      +/- 9 seconds, 6 of the 9 target VTs (67%) were rendered noninducible (4 of 4
      incessant VTs and 2 of 5 chronic recurrent VTs). In 6 patients, VTs with ECG
      morphologies other than the target VTs were inducible after RF catheter ablation.
      Seven patients were on antiarrhythmic drugs during the ablation procedure and
      during the follow-up period of 8 +/- 5 months (range, 2 to 17 months). One
      patient received an ICD before RF ablation, 4 patients after RF ablation, and 1
      patient after ablation of an incessant VT and before attempted ablation of
      frequent, recurrent VTs. One patient underwent heart transplantation 5 months
      after ablation in end-stage heart failure. There were no acute complications
      during the mapping and ablation procedure. During the follow-up period, 1 patient
      had been resuscitated from ventricular fibrillation 6 weeks after ablation and
      finally died of congestive heart failure 2 weeks later. No further episodes of
      incessant VT occurred in the patients who had undergone RF current application
      for ablation of incessant VT. A complete prevention of VT could be achieved in 2
      of 8 patients, whereas in 5 patients, VT episodes were stored in the ICD devices
      during follow-up. CONCLUSIONS: The results of the present study indicate that RF
      current application for ablation of VT in a select group of patients with
      idiopathic DCM is feasible. The efficacy of RF ablation may be high in patients
      presenting with incessant VT, whereas the success rate seems to be only moderate
      in patients with chronic recurrent VT. In all patients, additional treatment
      options, including antiarrhythmic drugs, ICDs, and/or heart transplantation, were
      applied after RF ablation, indicating that RF ablation for this indication may be
      an adjunctive and not a curative treatment option.

PMID- 7648662
TI  - Alterations in intracellular calcium handling associated with the inverse force
      frequency relation in human dilated cardiomyopathy.
AB  - BACKGROUND: The present study was performed to test the hypothesis that the
      altered force-frequency relation in human failing dilated cardiomyopathy may be
      attributed to alterations in intracellular calcium handling. METHODS AND RESULTS:
      The force-frequency relation was investigated in isometrically contracting
      ventricular muscle strip preparations from 5 nonfailing human hearts and 7 hearts
      with end-stage failing dilated cardiomyopathy. Intracellular calcium cycling was
      measured simultaneously by use of the bioluminescent photoprotein aequorin.
      Stimulation frequency was increased stepwise from 15 to 180 beats per minute (37
      degrees C). In nonfailing myocardium, twitch tension and aequorin light emission
      rose with increasing rates of stimulation. Maximum average twitch tension was
      reached at 150 min-1 and was increased to 212 +/- 34% (P < .05) of the value at
      15 min-1. Aequorin light emission was lowest at 15 min-1 and was maximally
      increased at 180 min-1 to 218 +/- 39% (P < .01). In the failing myocardium,
      average isometric tension was maximum at 60 min-1 (106 +/- 7% of the basal value
      at 15 min-1, P = NS) and then decreased continuously to 62 +/- 9% of the basal
      value at 180 min-1 (P < .002). In the failing myocardium, aequorin light emission
      was highest at 15 min-1. At 180 min-1, it was decreased to 71 +/- 7% of the basal
      value (P < .01). Including both failing and nonfailing myocardium, there was a
      close correlation between the frequencies at which aequorin light emission and
      isometric tension were maximum (r = .92; n = 19; P < .001). Action potential
      duration decreased similarly with increasing stimulation frequencies in
      nonfailing and end-stage failing myocardium. Sarcoplasmic reticulum 45Ca2+
      uptake, measured in homogenates from the same hearts, was significantly reduced
      in failing myocardium (3.60 +/- 0.51 versus 1.94 +/- 0.18 (nmol/L).min-1.mg
      protein-1, P < .005). CONCLUSIONS: These data indicate that the altered force
      frequency relation of the failing human myocardium results from disturbed
      excitation-contraction coupling with decreased calcium cycling at higher rates of
      stimulation.

PMID- 7648663
TI  - Repolarizing K+ currents in nonfailing human hearts. Similarities between right
      septal subendocardial and left subepicardial ventricular myocytes.
AB  - BACKGROUND: Studies of cardiac K+ channels from animal models have documented
      tissue-dependent and species-dependent diversity in the types and properties of
      K+ channels responsible for the repolarization of cardiac action potentials.
      Recent reports of human ventricular K+ currents emphasized differences in
      transient outward K+ current (Ito1) recorded from left ventricular (LV)
      subendocardial and subepicardial myocytes. These myocytes are usually isolated
      only from the LV free wall. The surface of the interventricular septum is
      continuous with the endocardium of both ventricular chambers. However, the septum
      contracts in unison with the left ventricle and therefore might have electric
      properties consonant with this function. In this study, we compare the
      characteristics of human cardiac K+ currents (Ito1 and inward rectifier K+
      current [IK1]) of myocytes isolated from either the LV subepicardium or
      subendocardium of the right ventricular (RV) septum. METHODS AND RESULTS:
      Subendocardial tissues were obtained during routine biopsies of the right
      interventricular septum of seven heart transplant recipients. Subepicardial
      tissues were obtained from five patients with normal LV function during open
      heart surgery. IK1 amplitude was the same in myocytes isolated from both regions.
      Delayed rectifier K+ currents were small or absent in these cells. Ito1 was only
      slightly larger in LV subepicardial versus RV septal subendocardial myocytes. For
      example, at +60 mV, Ito1 was 7.2 +/- 0.4 pA/pF (n = 33) in subepicardial cells
      compared with 6.0 +/- 0.5 pA/pF (n = 36) in subendocardial cells. All
      characteristics of Ito1 examined, including the voltage dependence of activation
      and inactivation, rate of inactivation, and percent decline of peak current
      during repetitive pulsing, were similar in myocytes isolated from both regions.
      These findings are in contrast to previous studies that demonstrated that Ito1 of
      subendocardial myocytes isolated from the LV free wall of human hearts was
      smaller and that recovery from inactivation of this current was much slower
      compared with that observed in subepicardial myocytes. CONCLUSIONS: We conclude
      that the major repolarizing K+ currents in normal human ventricular myocytes are
      IK1 and Ito1 and that the properties of Ito1 of subendocardial cells isolated
      from the right interventricular septum are more similar to subepicardial cells
      than to subendocardial cells of the LV free wall. The similar electric properties
      shared by myocytes from these two regions may be functionally important inasmuch
      as the right side of the interventricular septum functions as an extension of the
      subepicardium of the left ventricle during the contractile cycle.

PMID- 7648664
TI  - Correlation of temperature and pathophysiological effect during radiofrequency
      catheter ablation of the AV junction.
AB  - BACKGROUND: Accelerated junctional rhythms have been observed before the
      development of AV nodal block during radiofrequency (RF) catheter ablation of the
      AV junction. However, the time course and temperatures required to induce an
      accelerated junctional rhythm and AV nodal block during this procedure have not
      yet been characterized. METHODS AND RESULTS: Nineteen patients underwent RF
      ablation of the AV junction with a thermistor ablation catheter. RF energy was
      initially delivered at 10 W for 9 seconds and then increased by 5-W increments
      for 9 seconds at each power level up to a maximum power of 50 W. If a junctional
      rhythm was observed during the power titration, a 30- to 60-second RF application
      was then delivered at the same power level. The power was then further increased
      to a maximum of 50 W if AV nodal block was not observed after 20 seconds of RF
      delivery. The procedure was successful in all 19 patients. A median of one RF
      application (range, one to eight applications) was required to produce permanent
      AV nodal block. An accelerated junctional rhythm was observed during 89% of
      successful attempts versus 70% of unsuccessful deliveries (P = NS). The median
      time to onset of the junctional rhythm was significantly shorter during
      successful compared with unsuccessful applications (1.8 versus 7.7 seconds,
      respectively; P < .001). Similarly, the mean time to appearance of AV nodal block
      was significantly shorter during successful compared with unsuccessful attempts
      (19.6 +/- 9.4 versus 36.8 +/- 19.0 seconds, respectively; P < .01). The catheter
      tip temperatures associated with the development of an accelerated junctional
      rhythm were significantly lower than those associated with the appearance of AV
      nodal block (51 +/- 4 degrees C versus 58 +/- 6 degrees C, respectively; P <
      .001). Mean temperatures in the range of 60 +/- 7 degrees C were required to
      produce permanent AV nodal block. CONCLUSIONS: The development of an accelerated
      junctional rhythm within 5 seconds and the appearance of AV nodal block within 30
      seconds of RF onset were both highly characteristic of successful target sites
      during RF ablation of the AV junction. The accelerated junctional rhythm and AV
      nodal block were both highly temperature dependent. The temperatures associated
      with the onset of AV nodal block were significantly higher than the temperatures
      resulting in an accelerated junctional rhythm.

PMID- 7648665
TI  - Dynamic electrophysiological behavior of human atria during paroxysmal atrial
      fibrillation.
AB  - BACKGROUND: The aims of our study were to investigate the meaning of local atrial
      activation and its behavior during paroxysmal atrial fibrillation and to study
      the effect of overdrive pacing on local atrial activity. METHODS AND RESULTS:
      Twenty-five patients with lone paroxysmal atrial fibrillation underwent
      electrophysiological study. Functional and effective atrial refractoriness was
      determined. Mean and fifth percentile values of 100 consecutive atrial
      fibrillation intervals (FF) were evaluated at three atrial sites either at
      arrhythmia onset or at self-termination (or at minute 5). A high-voltage burst
      pacing was performed after 6 minutes of stable atrial fibrillation in 10
      patients. Mean FF intervals were evaluated 5 seconds before and after atrial
      pacing. Forty-nine atrial fibrillation episodes were induced: 39 self-terminating
      within 5 minutes and 10 long-lasting. A significant correlation was found between
      mean FF and atrial functional refractory period (r = .73, P < .001) and between
      fifth percentile FF and atrial effective refractory period (r = .57, P < .005).
      Atrial fibrillation self-termination was associated with significant mean FF
      prolongation, whereas long-lasting fibrillation behaved the opposite. In 10
      patients, burst pacing resulted in significant shortening of the mean FF at the
      stimulation site; no changes were observed in the two distant recording sites.
      CONCLUSIONS: The analysis of the FF intervals demonstrates a strict correlation
      with atrial functional refractoriness. The self-termination of atrial
      fibrillation is related to a prolongation of the functional refractoriness (mean
      FF), whereas a shortening of both functional and effective refractoriness (fifth
      percentile) is associated with atrial fibrillation persistence. The provoked
      shortening of the mean FF at the stimulation site is consistent with the presence
      of a gap of excitability during atrial fibrillation in the human atria.

PMID- 7648666
TI  - Morning peak in ventricular tachyarrhythmias detected by time of implantable
      cardioverter/defibrillator therapy. The CPI Investigators.
AB  - BACKGROUND: A morning peak in occurrence of sudden cardiac death has been
      identified in epidemiological studies, but the studies are subject to selection
      bias, with the exclusion of unwitnessed deaths, which are more likely to occur at
      night. The recent availability of implantable cardioverter/defibrillators that
      record the time of ventricular tachyarrhythmias requiring either pacing or shock
      therapy provides an opportunity to clarify the timing of ventricular
      tachyarrhythmias predisposing to sudden cardiac death. Analysis of the timing of
      arrhythmias in different patient subgroups, such as patients with poor left
      ventricular function, may provide further insight into the mechanism of onset of
      sudden cardiac death. METHODS AND RESULTS: We studied patients in whom a
      cardioverter/defibrillator (Ventak PRx) was implanted between September 1990 and
      September 1993 in US centers. Events that could be timed occurred in 483
      patients. With an RR cycle length of 240 ms as a cutoff, corresponding to a heart
      rate of 250 beats per minute, episodes were categorized as rapid (n = 1217) or
      less rapid (n = 9266) ventricular tachyarrhythmias. A higher proportion of both
      rapid and less rapid ventricular tachyarrhythmias began in the late morning
      compared with other times of the day. The subgroup of patients with ejection
      fraction < 20% at the time of implantation demonstrated a more uniform 24-hour
      distribution of tachycardias < or = 250 beats per minute than patients with
      higher left ventricular ejection fraction. CONCLUSIONS: Further investigation of
      the late morning peak and of precipitants of ventricular tachyarrhythmias by use
      of data from the implantable cardioverter/defibrillator may provide insight into
      the pathophysiological mechanisms causing sudden cardiac death.

PMID- 7648667
TI  - Gender-specific criteria and performance of the exercise electrocardiogram.
AB  - BACKGROUND: Significant gender differences have been found in performance of the
      exercise ECG for the identification of coronary artery disease. However,
      identical exercise ECG ST segment criteria have been used in men and women, which
      might contribute to the lower accuracy of these methods in women than in men.
      METHODS AND RESULTS: To assess the effect of gender-specific test partitions on
      relative performance of standard and heart rate-adjusted ST segment depression
      criteria in men and women, the exercise ECGs of 143 women and 477 men were
      examined. Non-gender-specific test partitions, selected to have matched
      specificities of 96% for each test method, were determined in all 283 normal
      subjects, and gender-specific test partitions with identical specificity were
      determined separately in the 52 normal women and 231 normal men; sensitivity of
      these criteria was then examined in the 91 women and 246 men with coronary
      disease. Standard ST segment depression criteria (0.1 mV of additional horizontal
      or downsloping ST segment depression at end exercise) with identical 96%
      specificity in the entire group of normal subjects and separately in women and
      men had a significantly lower sensitivity of 51% in women compared with 67% in
      men (P < .01). Among women, performance of the ST segment/heart rate (ST/HR)
      slope was more improved than that of the ST/HR index by the use of gender
      specific criteria. Compared with the performance of non-gender-specific criteria,
      application of gender-specific ST/HR slope partitions with matched specificity of
      96% resulted in a significant increase in sensitivity in women from 84% to 91% (P
      < .01), with no significant change in sensitivity in men (89% to 88%) and with no
      residual difference in sensitivity between men and women. Although the use of
      gender-specific ST/HR slope criteria significantly improved sensitivity in both
      men and women with respect to standard criteria (each P < .0001), the relative
      increase in sensitivity provided by heart rate adjustment was significantly
      greater in women than in men (40% versus 21%, P < .001). Similar gender
      differences in improvement in performance using gender-specific criteria for the
      ST/HR slope were observed when analysis of test performance was restricted to the
      detection of three-vessel coronary disease (50% versus 9%, P = .002).
      CONCLUSIONS: At high specificity, gender-specific test partitions improve
      sensitivity of the ST/HR slope for the identification of coronary disease in
      women, with no decrease in sensitivity in men. In contrast, gender-specific
      partitions do not change performance of standard test criteria, which is lower in
      women than in men. Accordingly, the relative benefit of heart rate adjustment by
      the ST/HR slope method is greater in women than in men. These findings support
      use of the ST/HR slope with use of gender-specific partitions for the
      identification and quantification of coronary artery disease in both men and
      women.

PMID- 7648668
TI  - Hepatic venous blood and the development of pulmonary arteriovenous malformations
      in congenital heart disease.
AB  - BACKGROUND: Pulmonary arteriovenous malformations (PAVMs) are a known
      complication after some types of cavopulmonary anastomoses (CVPAs). Their cause
      is unknown, but they may be related to the absence of pulsatile flow or the
      presence or absence of circulating factors. These PAVMs are diffuse and are
      presumed to be progressive and irreversible. METHODS AND RESULTS: All patients
      with congenital heart disease (CHD) seen at Children's Hospital, Boston, Mass,
      between 1970 and 1993 were reviewed. We report on the 10 patients with CHD who
      were found to have developed PAVMs, as diagnosed by cardiac catheterization.
      Diagnoses included heterotaxy syndrome/polysplenia, with interrupted inferior
      vena cava and hepatic veins draining to the right atrium (n = 6);
      heterotaxy/asplenia (n = 1); corrected transposition with pulmonary stenosis (n =
      1); and biliary atresia and associated CHD (n = 2). PAVMs were diagnosed 0.1 to
      7.0 years (median, 3.5 years) after creation of a CVPA that resulted in exclusion
      of hepatic venous flow from one or both lungs in 8 of the 10 patients; the
      remaining 2 patients had normal drainage of hepatic veins to the lungs but had
      biliary atresia. In all, the common anatomic feature was the exclusion of normal
      hepatic venous return from the affected pulmonary arterial circulation. All
      patients with interrupted inferior vena cava, azygous continuation to the
      superior vena cava, and hepatic veins draining to the right atrium (polysplenia
      syndrome) were reviewed to determine the incidence of PAVMs in those with CVPA
      (ie, hepatic venous flow excluded from the pulmonary arteries) and without CVPA.
      Six of 28 (21%) of those with versus 1 of 56 (1.8%) of those without CVPA
      developed PAVMs (P = .004). The 1 patient without CVPA who had PAVMs also had
      biliary atresia. Among patients with CVPA, the probability of developing PAVMs
      was 15% and 28% at 3 and 5 years, respectively, after CVPA. The histological and
      angiographic appearances of PAVMs after CVPA are similar to those seen in PAVMs
      associated with hepatic cirrhosis. CONCLUSIONS: We postulate that PAVMs after
      CVPA are related to the diversion of normal hepatic venous flow from the
      pulmonary circulation. In this sense, these PAVMs may be analogous to those
      associated with liver disease, which have been found to resolve after liver
      transplantation. Redirection of hepatic flow to the pulmonary bed in some
      patients with CHD and PAVMs may lead to reversibility of the PAVMs.

PMID- 7648669
TI  - Acute hypertension induces heat-shock protein 70 gene expression in rat aorta.
AB  - BACKGROUND: Many factors cause acute systemic hypertension, which in turn can
      result in damage to the vessel wall and lead to vascular disease. In previous
      studies, we demonstrated that restraint, or immobilization stress, results in the
      induction of heat-shock protein 70 (hsp70) gene expression in the aorta of adult
      rat and showed that this response was markedly attenuated with age. METHODS AND
      RESULTS: Here we provide evidence that restraint-induced hsp70 expression occurs
      secondary to a rise in systemic blood pressure. Old rats were unable to mount a
      significant stress-induced hypertensive response, providing an explanation for
      the reduced hsp70 response in the old rats. A variety of vasoactive agents that
      induce acute hypertension through distinct signal transduction pathways,
      including phenylephrine, dopamine, vasopressin, angiotensin II, and endothelin-1,
      were found to result in hsp70 mRNA induction in the aorta. The magnitude of hsp70
      expression achieved with these hypertensive agents was directly correlated with
      their relative effects on blood pressure. Rats were treated with the vasodilator
      sodium nitroprusside, which prevented an acute rise in blood pressure from the
      hypertensive agents tested and abolished induction of hsp70 expression.
      CONCLUSIONS: These findings support the conclusion that hsp70 induction occurs as
      a physiological response to acute hypertension and suggest the possibility that
      hsp70 plays a role in the protecting the vasculature from damage during
      hemodynamic stress.

PMID- 7648670
TI  - Smooth muscle cell proliferation is proportional to the degree of balloon injury
      in a rat model of angioplasty.
AB  - BACKGROUND: A variable degree of smooth muscle cell (SMC) proliferation after
      balloon injury has been reported in previous rat studies. It is unknown whether
      balloon injury induces c-fos expression and whether it is related to the degree
      of vascular injury in vivo. Therefore, we tested the hypothesis that proportional
      increases in neointimal formation and c-fos expression might be present after
      different degrees of balloon dilation. METHODS AND RESULTS: Angioplasty of the
      carotid artery was performed with a balloon catheter. Vascular injury was
      evaluated at 0, 0.5, 1.0, 1.5, and 2 atm (n = 6 for all). In 40 additional rats,
      total RNA dot blots were performed to assess the effect of various degrees of
      balloon injury on c-fos expression. SMC proliferation proportional to the
      increases of inflation pressure was found between 0 and 2 atm with neointimal
      areas of 0.002 +/- 0.002, 0.069 +/- 0.014, 0.128 +/- 0.043, 0.190 +/- 0.010, and
      0.255 +/- 0.041 mm2, respectively. When the degree of SMC proliferation
      (neointima and neointima/media ratio) was plotted against balloon inflation
      pressure, a linear relation was observed (r = .733, P < .001 and r = .755, P <
      .001, respectively). An increase in c-fos expression proportional to the degree
      of injury was found 30 minutes after injury. CONCLUSIONS: Neointimal
      proliferation produced by balloon injury is related to balloon inflation
      pressure, supporting the concept of an SMC proliferative response proportional to
      the degree of injury. The increase in SMC proliferation is associated with a
      proportional increase in the early expression of the c-fos nuclear proto
      oncogene.

PMID- 7648671
TI  - Bimakalim, an ATP-sensitive potassium channel opener, mimics the effects of
      ischemic preconditioning to reduce infarct size, adenosine release, and
      neutrophil function in dogs.
AB  - BACKGROUND: The primary goal of the present study was to determine whether the
      infarct size-reducing effect of preconditioning is associated with an increase in
      adenosine release from the ischemic myocardium during a prolonged occlusion
      period or the subsequent reperfusion period and by a decrease in neutrophil
      infiltration. A second objective was to determine whether bimakalim, a KATP
      channel opener, mimics the effects of ischemic preconditioning. METHODS AND
      RESULTS: Barbital-anesthetized open-chest dogs were subjected to 60 minutes of
      left anterior descending coronary artery (LAD) occlusion followed by 3 hours of
      reperfusion. In the preconditioning group, 5 minutes of LAD occlusion followed by
      10 minutes of reperfusion was elicited before the 60-minute occlusion period. In
      two other groups, bimakalim 1 microgram/kg bolus followed by a 0.05 micrograms.kg
      1.min-1 infusion or an equivalent volume of saline was administered intravenously
      15 minutes before occlusion and continued until the time of reperfusion. In a
      final group, bimakalim was administered 10 minutes before reperfusion and
      continued until the end of the experiment. To measure the release of adenosine
      from the ischemic region, coronary venous blood samples were collected at various
      times during ischemia and after reperfusion, and the concentration of adenosine
      was measured. Myocardial infarct size was determined by triphenyl tetrazolium
      chloride; transmural myocardial blood flow, by radioactive microspheres.
      Transmural myeloperoxidase (MPO) activity, an index of neutrophil infiltration in
      the area at risk, was also measured. Preconditioning produced a marked reduction
      in infarct size (9.8 +/- 3.0% versus 28.6 +/- 5.2% in the control group, mean +/-
      SEM); adenosine release at 5, 10, 15, and 30 minutes of the 3-hour reperfusion
      period; and transmural MPO activity in the risk area. Similarly, pretreatment
      with bimakalim resulted in reductions in infarct size, adenosine release, and
      transmural MPO activity to an extent almost identical to that of preconditioning.
      When bimakalim was administered 10 minutes before reperfusion, the drug also
      produced a significant reduction in infarct size and transmural MPO activity;
      however, no significant reduction in coronary venous adenosine concentrations was
      observed. There were no significant differences in collateral blood flow between
      groups. CONCLUSIONS: These results indicate that myocardial preconditioning in
      the canine heart produced by a short period of ischemia or a KATP channel opener
      is not mediated by an increase in adenosine release, as measured by coronary
      venous adenosine concentrations, during 60 minutes of occlusion or the initial 30
      minutes of reperfusion. A significant reduction in transmural MPO activity in the
      ischemic area also appears to result from KATP channel activation and may play a
      role, at least in part, in the reduction in infarct size observed, particularly
      when a KATP channel opener is administered just before reperfusion.

PMID- 7648672
TI  - Myocardial kinetics of a putative hypoxic tissue marker, 99mTc-labeled
      nitroimidazole (BMS-181321), after regional ischemia and reperfusion.
AB  - BACKGROUND: A new nitroimidazole complex, 99mTc-propylene amine oxime-1,2
      nitroimidazole (BMS-181321), has been developed to allow the positive imaging of
      hypoxic myocardium by standard gamma camera techniques. METHODS AND RESULTS: To
      determine the myocardial kinetics of BMS-181321 during myocardial ischemia and
      reperfusion, seven open-chest swine were prepared according to a model of
      extracorporeal coronary perfusion in which left ventricular wall thickening
      (percent end-diastolic thickness) and substrate use in the left anterior
      descending (LAD) region ([14C]palmitate and [3H]glucose infusions) were
      determined. Measurements were obtained at baseline, during 40 minutes of ischemia
      produced by reducing flow in the LAD distribution by 60%, and during 70 minutes
      of reperfusion. Three aerobic control hearts were also studied in which LAD blood
      flow was not reduced. Regional coronary circulation was further assessed in all
      hearts by use of radiolabeled microspheres injected during ischemia. BMS-181321
      (20 to 30 mCi) was injected after 30 minutes of ischemia, and its myocardial
      uptake was assessed by dynamic planar gamma imaging. Ischemia was associated with
      declines in fatty acid metabolism (15 +/- 11 mumol.h-1.g dry wt-1, mean +/- SEM),
      systolic wall thickening (20 +/- 6%), and myocardial oxygen consumption (3 +/- 1
      mL.min-1.100 g-1) and an increase in exogenous glucose utilization (75 +/- 13
      mumol.h-1.g dry wt-1). Systolic wall thickening recovered by only 8 +/- 3% with
      reperfusion. Initial distribution of BMS-181321 in the aerobic hearts appeared
      homogeneous. Washout from the ischemic and reperfused LAD bed was slower than the
      aerobically perfused LAD bed in the control group (t1/2 = 136 +/- 1 versus 80 +/-
      1 minutes, P < .05), allowing visualization of the LAD region during reperfusion.
      Tissue activity of BMS-181321 was inversely related to LAD blood flow during
      ischemia (r = -.68 +/- .05), and the ratio of BMS-181321 in the LAD region versus
      normal myocardium was 1.7 +/- 0.2. Control swine lacked regional deposition of
      the tracer in the normally perfused LAD distribution. CONCLUSIONS: Thus, acute
      regional ischemia in these studies was visualized as an increase in retention of
      BMS-181321, suggesting its applicability in the imaging of clinical conditions of
      myocardial hypoperfusion.

PMID- 7648673
TI  - Bidirectional effects of aminophylline on myocardial ischemia.
AB  - BACKGROUND: Aminophylline blocks adenosine receptors and increases levels of
      plasma catecholamines. We investigated the effect of aminophylline on myocardial
      ischemia by varying its severity and attempted to identify the mechanism by which
      aminophylline modulates myocardial ischemia in the canine model. METHODS AND
      RESULTS: In 41 open-chest dogs, the left anterior descending coronary artery was
      cannulated and perfused with blood through a bypass tube from the left carotid
      artery. When coronary blood flow (CBF) was reduced to 80% of the control,
      aminophylline increased fractional shortening (FS) from 11.0 +/- 0.4% to 18.5 +/-
      1.7% (P < .05) and lactate extraction ratio (LER) from 7.5 +/- 0.1% to 13.6 +/-
      1.0% (P < .01). The endocardial to epicardial flow ratio (Endo/Epi ratio) of
      regional myocardium was also increased. Release of adenosine was increased
      compared with the nonischemic condition (7 +/- 3 versus 28 +/- 5 pmol/mL).
      Prazosin, an alpha 1-adrenoceptor antagonist, blunted the aminophylline-induced
      improvement in contractile and metabolic function. Administration of 8
      phenyltheophylline, a selective antagonist of adenosine receptors, did not
      increase FS, LER, or the Endo/Epi ratio when CBF was reduced to 80% of control.
      When CBF was reduced to 60% of control, aminophylline did not change the
      metabolic and contractile function. In contrast, when CBF was reduced to 33% of
      control, release of adenosine was increased markedly (243 +/- 19 pmol/mL) and
      aminophylline induced decreases in FS, LER, and Endo/Epi ratio similar to those
      observed with 8-phenyltheophylline. CONCLUSIONS: Aminophylline had opposite
      effects on the ischemic myocardium depending on the severity of ischemia. It
      improved mild ischemia but worsened severe ischemia. The beneficial effect of
      aminophylline was attributable to alpha 1-adrenoceptor stimulation, which
      improves endomyocardial flow in the ischemic myocardium. The deleterious effect
      was attributable to the aminophylline-induced blockade of adenosine receptors.

PMID- 7648674
TI  - Kinetic analysis of technetium-99m-labeled nitroimidazole (BMS-181321) as a
      tracer of myocardial hypoxia.
AB  - BACKGROUND: Experimental data have indicated that [99mTc]-nitroimidazole (BMS
      181321) is preferentially taken up in hypoxic tissue; its kinetics, however, has
      not been fully investigated. The purpose of this study was to address the
      relation between perfusate oxygen level and myocardial retention of
      [99mTc]nitroimidazole. METHODS AND RESULTS: Bolus injection and constant infusion
      experiments were performed in Langendorff buffer-perfused rat hearts in normoxic
      and hypoxic conditions. Data were acquired with a pair of NaI detectors. The
      initial clearance rate of [99mTc]nitroimidazole was approximately 20 seconds and
      independent of perfusate oxygen level. The slow clearance rate was greater than 3
      hours in all perfusion conditions. The tissue retention of [99mTc]nitroimidazole
      varied from 0.61 +/- 0.14% in normoxic conditions to 5.94 +/- 1.16% in the most
      severe hypoxic conditions. In addition, tissue retention was inversely
      proportional to perfusate oxygen level in a sigmoidal manner. The constant
      infusion experiments established that the binding rate at 25% oxygen level (1.94
      +/- 0.38 mL of perfusate/min-g dry wt) was twofold of that at 40% and sevenfold
      at 100%. The binding rate of [99mTc]nitroimidazole was independent of the
      perfusion sequence, suggesting irreversible binding. CONCLUSIONS: These data
      indicate that [99mTc]nitroimidazole may be a useful tracer for the identification
      of myocardial hypoxia. A sigmoidal relation was demonstrated for the uptake of
      the tracer, which suggests that a threshold level of hypoxia is necessary for the
      uptake of the tracer.

PMID- 7648675
TI  - VCL, an antagonist of the platelet GP1b receptor, markedly inhibits platelet
      adhesion and intimal thickening after balloon injury in the rat.
AB  - BACKGROUND: Arterial injury is immediately followed by platelet adhesion at the
      site of injury, a process that requires the interaction of subendothelial von
      Willebrand factor with the platelet GP1b receptor. VCL, a recombinant von
      Willebrand factor GP1b binding domain, inhibits platelet binding to von
      Willebrand factor. The aim of this study was to determine whether VCL inhibits
      platelet adhesion at the site of arterial injury and affects neointimal
      thickening after injury in rats. METHODS AND RESULTS: Sprague-Dawley rats were
      randomized to receive VCL, 4 mg/kg bolus followed by a continuous infusion of 2
      mg.kg-1.h-1 for 72 hours, or an identical volume of saline. Balloon injury of the
      femoral artery was performed 15 minutes after the initial bolus injection of VCL.
      Scanning electron microscopy performed 1 and 3 days after injury indicated that
      VCL-treated rats had > 80% reduction in the number of platelets adherent to the
      vessel wall at the site of injury compared with controls (P < .003). Histological
      examination at day 14 showed that, compared with controls, VCL-treated rats had a
      60% reduction in the intima-media ratio (0.21 +/- 0.03 versus 0.53 +/- 0.06, P =
      .001) and a reduced luminal area stenosis (12 +/- 3% versus 38 +/- 10%, P = .04).
      At 28 days after injury, there was no rebound of neointimal thickening in VCL
      treated rats (intima-media ratio, 0.19 +/- 0.04; luminal stenosis, 17 +/- 5%).
      The difference between VCL-treated rats and control rats persisted but was
      attenuated (intima-media ratio, 0.19 +/- 0.04 versus 0.28 +/- 0.1, P = .162;
      luminal stenosis, 17 +/- 5% versus 31 +/- 5%, P = .058) as neointimal thickening
      regressed in untreated rats. With the use of proliferating cell nuclear antigen
      immunohistochemistry on day 3, VCL had no effect on smooth muscle cell (SMC)
      proliferation. CONCLUSIONS: Antagonism of the platelet GP1b receptor by VCL
      profoundly decreased platelet deposition at the site of balloon injury in the rat
      femoral artery. This effect was associated with a persistent reduction in
      neointimal thickening. The lack of effect of VCL on SMC proliferation suggests
      that the decrease in neointimal thickening may have been mediated through
      inhibition of SMC migration and/or modulation of the extracellular matrix.

PMID- 7648676
TI  - Effect of left ventricular hypertrophy secondary to chronic pressure overload on
      transmural myocardial 2-deoxyglucose uptake. A 31P NMR spectroscopic study.
AB  - BACKGROUND: This study tested the hypothesis that 31P nuclear magnetic resonance
      (NMR)-detectable 2-deoxyglucose (2DG) uptake is increased in chronically pressure
      overloaded hypertrophied left ventricular myocardium. METHODS AND RESULTS: 31P
      NMR spectroscopy was used to determine the transmural distribution of high-energy
      phosphate levels and 2-deoxyglucose-6-phosphate (2DGP) accumulation during
      intracoronary infusion of 2DG (15 mumol.kg body wt-1.min-1) in eight normal dogs
      and in eight dogs with severe left ventricular hypertrophy (LVH) produced by
      ascending aortic banding. The ratio of LV weight to body weight was 8.25 +/- 0.65
      g/kg in the LVH group compared with 4.35 +/- 0.11 g/kg in the normal group (P <
      .01). Myocardial ATP content was decreased by approximately 40% and
      phosphocreatine (PCr) by approximately 60% in LVH hearts. ATP values were
      transmurally uniform in LVH and normal hearts, whereas PCr was lower in the
      subendocardium (Endo) than the subepicardium (Epi) of both groups. The PCr/ATP
      ratio was lower in LVH hearts (1.72 +/- 0.05, 1.64 +/- 0.07, and 1.53 +/- 0.10 in
      Epi, midwall, and Endo, respectively) compared with normal hearts (2.36 +/- 0.05,
      2.09 +/- 0.06, and 1.96 +/- 0.06; each P < .01 normal versus LVH). Arterial blood
      levels of glucose, insulin, and free fatty acids were comparable between groups,
      whereas arterial lactate and norepinephrine levels were significantly higher in
      the LVH group. 2DG infusion did not affect systemic hemodynamics or myocardial
      high-energy phosphate or inorganic phosphate levels in either group. At the end
      of 60 minutes of 2DG infusion, there was no detectable accumulation of 2DGP in
      the normal hearts. However, seven of the eight LVH hearts showed time-dependent
      accumulation of 2DGP, which was linearly related to the severity of hypertrophy
      (r = .90 for subendocardial 2DGP versus LV weight/body weight). A transmural
      gradient of 2DGP was present, with greatest accumulation in the subendocardium
      (3.3 +/- 1.6, 5.8 +/- 2.3, and 7.9 +/- 2.2 mumol/g in Epi, midwall, and Endo of
      the LVH hearts, respectively; P < .05 Epi versus Endo). CONCLUSIONS: The pressure
      overloaded hypertrophied left ventricle demonstrated increased accumulation of
      2DGP detected with 31P NMR spectroscopy. Accumulation of 2DGP was positively
      correlated with the degree of hypertrophy and was most marked in the
      subendocardium.

PMID- 7648677
TI  - Isolated systolic and diastolic ventricular interactions in pacing-induced
      dilated cardiomyopathy and effects of volume loading and pericardium.
AB  - BACKGROUND: Interactions between the closely coupled right and left ventricles
      are known to play important roles as determinants of ventricular function, and
      the purpose of this study was to evaluate their effects in a model of heart
      failure. METHODS AND RESULTS: A dilated cardiomyopathy resulting in congestive
      heart failure (CHF) was produced in pigs by rapid ventricular pacing at 230 beats
      per minute for 1 week. Blood was rapidly withdrawn from the left ventricular (LV)
      apex into a prosthetic ventricle, and the instantaneous effects on the right
      ventricle were studied during volume loading and before and after
      pericardiectomy. The systolic interaction gain between the right and left
      ventricles (Gs) was calculated as the ratio of changes in mean systolic pressure
      during isolated systolic LV unloading. Diastolic ventricular interaction gain
      (Gd) was calculated as the ratio of changes in mean diastolic pressures during LV
      unloading in the last 150 ms of diastole. With the pericardium closed, all
      interaction gains were significantly increased during volume loading from a right
      ventricular end-diastolic pressure of 3 to 9 mm Hg: Gs from 0.045 +/- 0.014 to
      0.063 +/- 0.020 mm Hg/mm Hg (normal pigs) and from 0.077 +/- 0.040 to 0.103 +/-
      0.019 (CHF pigs) and Gs from 0.196 +/- 0.116 to 0.493 +/- 0.117 mm Hg/mm Hg
      (normal pigs) and from 0.174 +/- 0.101 to 0.341 +/- 0.165 (CHF pigs). When the
      pericardium was opened, Gd was significantly reduced to 0.145 +/- 0.071 and 0.129
      +/- 0.026 mm Hg/mm Hg (normal and CHF pigs, respectively), but Gs showed no
      significant change (0.067 +/- 0.027 and 0.109 +/- 0.012 mm Hg/mm Hg for normal
      and CHF pigs, respectively), and both were also significantly increased during
      volume loading. Gs was significantly greater in CHF versus normal pigs under all
      conditions, but there were no differences in Gd between CHF and normal pigs.
      CONCLUSIONS: These results suggest that dilated cardiomyopathy increases systolic
      but not diastolic interactions, that the pericardium increases diastolic but not
      systolic ventricular interactions, and that volume loading with and without the
      pericardium opened increases both systolic and diastolic interactions.

PMID- 7648678
TI  - Effect of rapid pacing and T-wave scanning on the relation between the
      defibrillation and upper-limit-of-vulnerability dose-response curves.
AB  - BACKGROUND: The critical-point and upper-limit-of-vulnerability (ULV) hypotheses
      predict that the ULV dose-response curve should be steeper and to the right of
      the defibrillation (DF) curve. Yet, some recent experimental data contradict this
      prediction. Two studies are presented that test two explanations for the
      contradiction: (1) Testing at a single point in the T wave underestimates the ULV
      dose-response curve and (2) ULV testing at normal heart rates does not mimic the
      mechanical or electrical state of the heart in ventricular fibrillation (VF).
      METHODS AND RESULTS: A nonthoracotomy lead system with a biphasic waveform was
      used throughout. In eight dogs, the dose-response curve widths (a measure of
      steepness) were compared between DF data and ULV data gathered at the peak
      (ULVPK), middownslope (ULVDWN), midupslope (ULVUP), and all times (scanning or
      ULVSCN) in the T wave. In another eight dogs, ULV data (ULVRAP) were gathered by
      scanning the T wave after 15 rapidly paced beats (166- to 198-ms pacing
      interval). The rapid pacing interval was chosen to more closely mimic the
      hemodynamics and activation rate of early VF. ULV data (ULVSTD) at normal heart
      rates were gathered for all animals. In the first study, scanning significantly
      reduced the ULV curve width (ULVSCN, 63.5 +/- 29.7 V; ULVPK, 81.9 +/- 45.2 V;
      ULVDWN, 116 +/- 36.5 V; DF, 105 +/- 22.0 V; P < .03) and significantly shifted
      the ULV curve to the right (ULV80 SCN, 410 +/- 62.6 V; ULV80 PK, 266 +/- 35.3 V;
      ULV80 DWN, 355 +/- 80.4 V; DF80, 427 +/- 60.9 V; P < .001). The subscript 80
      signifies that the subject was left in normal sinus rhythm 80% of the time after
      that stimulus strength was delivered. In the second study, the ULVRAP curve was
      shifted dramatically to the right, the average ULV50 RAP being greater than the
      average DF90. Furthermore, 92% of the ULVRAP VF inductions occurred between 10 ms
      before and 50 ms after the peak of the T wave, suggesting that scanning of the
      entire T wave may not be necessary. CONCLUSIONS: With a single rapidly paced ULV
      sequence with limited T-wave scanning, it may be possible to estimate highly
      effective defibrillation doses with few VF episodes and high-voltage stimuli.

PMID- 7648679
TI  - Determinants and mechanisms of flecainide-induced promotion of ventricular
      tachycardia in anesthetized dogs.
AB  - BACKGROUND: Class IC antiarrhythmic agents such as flecainide are known to have
      potentially significant ventricular proarrhythmic actions, but the underlying
      mechanisms are incompletely understood. While some studies have reported
      proarrhythmia in both healthy dogs and dogs that previously have had a myocardial
      infarction (MI), there are no published, controlled studies comparing
      proarrhythmia in healthy dogs vs in dogs with MI. In addition, the concentration
      dependence of proarrhythmia is unknown and the electrophysiological changes
      associated with proarrhythmia are not well established. METHODS: We administered
      successive loading and maintenance infusions of flecainide until ventricular
      tachyarrhythmia or death occurred in 13 healthy dogs and 19 dogs with 72-hour-old
      MIs (MI dogs). Ventricular proarrhythmia, defined as reproducible ventricular
      tachycardia absent under control conditions and occurring in the presence of
      flecainide, was observed in 4 of 13 healthy dogs (31%) and 15 of 19 MI dogs (79%,
      P = .02), and drug-induced spontaneous ventricular tachycardia occurred in 8 of
      19 MI dogs but in no healthy dogs (P = .007). Activation data at the time of
      proarrhythmia were available for 11 MI dogs and provided evidence for reentry in
      9, with a complete epicardial reentry circuit identified in 4 dogs and a partial
      circuit in 5. While flecainide slowed ventricular conduction in both the
      longitudinal and transverse directions, there were no significant differences
      between overall drug-induced conduction changes in MI dogs compared with healthy
      dogs. However, in 7 MI dogs for whom activation data were available during
      ventricular pacing at concentrations comparable to those causing proarrhythmia,
      flecainide induced a new arc of block in 6 of 7, whereas an arc of block was
      never observed in the absence of proarrhythmia. Conduction block was induced
      transverse to fiber orientation in a rate-dependent fashion and was caused by a
      regionally-specific effect of the drug. No differences were noted between
      refractory periods proximal and distal to the site of block. CONCLUSIONS: Prior
      MI strongly predisposes dogs to flecainide proarrhythmia, which occurs in the
      majority of such dogs in a concentration-related way. In most cases, activation
      data suggest that anisotropic reentry around a localized arc of rate-dependent
      transverse conduction block underlies proarrhythmia. These results provide
      insights into the conditions and mechanisms underlying the ability of flecainide
      to promote the occurrence of ventricular tachycardia.

PMID- 7648680
TI  - Linear ablation of the isthmus between the inferior vena cava and tricuspid
      annulus for the treatment of atrial flutter. A study in the canine atrial flutter
      model.
AB  - BACKGROUND: The isthmus between the inferior vena cava and the tricuspid annulus
      has been shown to be involved in the reentry circuit of common atrial flutter.
      The effects of radio-frequency catheter ablation of this isthmus were examined in
      the canine model of atrial flutter due to reentry around the tricuspid annulus.
      METHODS AND RESULTS: A model of atrial flutter was prepared in 11 of 14 dogs by
      creating intercaval and connected transverse lesions (Y-shaped lesion). Bipolar
      electrodes were attached at 24 atrial sites, and computer-assisted mapping was
      performed. Stable atrial flutter with a cycle length of 133 +/- 11 ms was
      repeatedly induced by rapid atrial pacing in all dogs, and atrial mapping
      revealed reentry around the tricuspid annulus including the isthmus. In 6 dogs,
      the isthmus was ligated during atrial flutter (mechanical ablation). In the other
      5 dogs, a 7F large-tip electrode catheter was placed at the isthmus under a
      fluoroscopic control. Radiofrequency energy (25 W for 30 s) was delivered to
      three sequential sites from the tricuspid annulus to the inferior vena cava to
      ablate the isthmus linearly. Atrial flutter was terminated in all dogs after
      mechanical and radio-frequency ablation of the isthmus and was not induced again.
      Atrial pacing from the posterior left atrium during sinus rhythm demonstrated
      intra-atrial conduction block at the isthmus after ablation. Pathological
      examination of the isthmus showed transmural myocardial damage. CONCLUSIONS:
      Linear radiofrequency ablation of the isthmus can induce intra-atrial conduction
      block and is effective as a curative therapy for atrial flutter when the reentry
      circuit involves the isthmus.

PMID- 7648681
TI  - Visualization of thrombi in pulmonary arteries with radiolabeled, enzymatically
      inactivated tissue-type plasminogen activator.
AB  - BACKGROUND: Despite the high frequency of pulmonary thromboembolism and its
      significant morbidity and mortality, diagnosis remains suboptimal. We have been
      developing a method for prompt detection with the use of radiolabeled,
      inactivated tissue-type plasminogen activator (TPA) and performed the present
      study to determine whether its use permits rapid scintigraphic visualization of
      pulmonary thrombi in vivo. METHODS AND RESULTS: The thrombolytic, but not fibrin
      binding, property of TPA was inactivated with a tripeptide chloromethyl ketone
      (YPACK) that had already been iodinated with 123I to radiolabel the TPA.
      Pulmonary arterial thrombosis was induced in nine dogs with the use of guide
      wires modified to provide thrombogenic tips. 123I-YPACK-TPA (1.1 to 7.8 mCi, 0.5
      to 7.8 mg) was infused for 5 minutes into either the systemic or the pulmonary
      circulation. Clearance of radioactivity from the blood was rapid and
      indistinguishable from that of unlabeled, thrombolytically active TPA, with only
      6.7 +/- 1.0% (mean +/- SEM) of peak radioactivity remaining after 60 minutes and
      minimal release of labeled fragments from the liver during this interval. Thrombi
      were visualized with single photon emission computed tomography and/or planar
      imaging 40 to 120 minutes after infusion of tracer in all seven animals given at
      least 3.7 mCi of 123I-YPACK-TPA. Ratios of radioactivity in thrombus (wet mass,
      610 +/- 64 mg) to blood were high (14 +/- 3:1). CONCLUSIONS: The use of
      radiolabeled TPA in which thrombolytic activity is inactivated permits prompt
      scintigraphic detection of thrombi in pulmonary arteries in vivo.

PMID- 7648682
TI  - Nifedipine. Dose-related increase in mortality in patients with coronary heart
      disease.
AB  - BACKGROUND: The purpose of this study was to assess the effect of the dose of
      nifedipine, a dihydropyridine calcium antagonist, on the increased risk of
      mortality seen in the randomized secondary-prevention trials and to review the
      mechanisms by which this adverse effect might occur. METHODS AND RESULTS: We
      restricted the dose-response meta-analysis to the 16 randomized secondary
      prevention trials of nifedipine for which mortality data were available. Recent
      trials of any calcium antagonist and formulation were also reviewed for
      information about the possible mechanisms of action that might increase
      mortality. Overall, the use of nifedipine was associated with a significant
      adverse effect on total mortality (risk ratio, 1.16, with a 95% CI of 1.01 to
      1.33). This summary estimate fails to draw attention to an important dose
      response relationship. For daily doses of 30 to 50, 60, and 80 mg, the risk
      ratios for total mortality were 1.06 (95% CI, 0.89 to 1.27), 1.18 (95% CI, 0.93
      to 1.50), and 2.83 (95% CI, 1.35 to 5.93), respectively. In a formal test of dose
      response, the high doses of nifedipine were significantly associated with
      increased mortality (P = .01). While the mechanism of this adverse effect is not
      known, there are several plausible explanations, including the established
      proischemic effect, negative inotropic effects, marked hypotension, recently
      reported prohemorrhagic effects attributed to antiplatelet and vasodilatory
      actions of calcium antagonists, and possibly proarrhythmic effects. CONCLUSIONS:
      In patients with coronary disease, the use of short-acting nifedipine in moderate
      to high doses causes an increase in total mortality. Other calcium antagonists
      may have similar adverse effects, in particular those of the dihydropyridine
      type. Long-term safety data are lacking for most calcium antagonists.

PMID- 7648683
TI  - Electrophysiological testing. The final court of appeal for diagnosis of syncope?

PMID- 7648684
TI  - Recent advances in the molecular genetics of hypertrophic cardiomyopathy.

PMID- 7648685
TI  - Images in cardiovascular medicine. Prosthetic heart valve thrombosis.

PMID- 7648686
TI  - Cardiogenic shock and early revascularization.

PMID- 7648687
TI  - Chelation therapy.

PMID- 7648688
TI  - Effectiveness of EDTA chelation therapy.

PMID- 7648689
TI  - Dobutamine echocardiography.

PMID- 7648690
TI  - Beta-particle emission from stent wire.

PMID- 7648691
TI  - A definition of advanced types of atherosclerotic lesions and a histological
      classification of atherosclerosis. A report from the Committee on Vascular
      Lesions of the Council on Arteriosclerosis, American Heart Association.
AB  - This report is the continuation of two earlier reports that defined human
      arterial intima and precursors of advanced atherosclerotic lesions in humans.
      This report describes the characteristic components and pathogenic mechanisms of
      the various advanced atherosclerotic lesions. These, with the earlier definitions
      of precursor lesions, led to the histological classification of human
      atherosclerotic lesions found in the second part of this report. The Committee on
      Vascular Lesions also attempted to correlate the appearance of lesions noted in
      clinical imaging studies with histological lesion types and corresponding
      clinical syndromes. In the histological classification, lesions are designated by
      Roman numerals, which indicate the usual sequence of lesions progression. The
      initial (type I) lesion contains enough atherogenic lipoprotein to elicit an
      increase in macrophages and formation of scattered macrophage foam cells. As in
      subsequent lesion types, the changes are more marked in locations of arteries
      with adaptive intimal thickening. (Adaptive thickenings, which are present at
      constant locations in everyone from birth, do not obstruct the lumen and
      represent adaptations to local mechanical forces). Type II lesions consist
      primarily of layers of macrophage foam cells and lipid-laden smooth muscle cells
      and include lesions grossly designated as fatty streaks. Type III is the
      intermediate stage between type II and type IV (atheroma, a lesion that is
      potentially symptom-producing). In addition to the lipid-laden cells of type II,
      type III lesions contain scattered collections of extracellular lipid droplets
      and particles that disrupt the coherence of some intimal smooth muscle cells.
      This extracellular lipid is the immediate precursor of the larger, confluent, and
      more disruptive core of extracellular lipid that characterizes type IV lesions.
      Beginning around the fourth decade of life, lesions that usually have a lipid
      core may also contain thick layers of fibrous connective tissue (type V lesion)
      and/or fissure, hematoma, and thrombus (type VI lesion). Some type V lesions are
      largely calcified (type Vb), and some consist mainly of fibrous connective tissue
      and little or no accumulated lipid or calcium (type Vc).

PMID- 7648692
TI  - [Influence of radiotherapy and chemotherapy on the function of malignant tumor
      patients and regulation function of acupuncture].
AB  - The observation on the indexes of cortisol, estradiol, estriol and testosterone
      showed that incretory function of malignant tumor patients had different extent
      of pathologic changes, after radiotherapy and chemotherapy, making the change
      strengthened. Acupuncture can regularize this disorder of incretory function of
      patients treated with radiotherapy and chemotherapy to some extent.

PMID- 7648693
TI  - [Involvement of opioid peptides in corticofugal modulation of pain].
AB  - The effect of opioid peptides on corticofugal modulation of nociceptive response
      in thalamic ventrobasal nucleus (VB) produced by cortical sensorimotor area II
      (Sm II) was observed. Single unit activities of VB neurons were extracellularly
      recorded by glass microelectrodes. The results showed that the nociceptive
      responses of VB neurons were attenuated at 0-7.5 minutes after stimulating Sm II
      (n = 14, P < 0.05). The inhibitory effect of stimulation of Sm II was reduced
      after ventriculer microinjection of 20ul of naloxone (n = 9), while marked
      inhibition was shown at 0-2.5 minutes after stimulating Sm II in the saline
      control group (n = 9, P < 0.05). There was a statistical difference at 0-2.5
      minutes after stimulating Sm II between the two groups (P < 0.05). These studies
      suggest that opioid peptides might be involved in corticofugal modulation of
      pain.

PMID- 7648694
TI  - [Influence of SmI lesion on acupuncture-induced analgesia in thalamic Pf neurons
      and effects of iontophoretic ACh on their nociceptive responses].
AB  - This study aimed to investigate the role of ACh in SmI emanating descending
      modulation of thalamic Pf neurons in acupuncture analgesia. Multi-micropipettes
      were used for both extracellularly recording responses of thalamic Pf neurons to
      noxious stimulation of the plantar area and drug application in rats. It was
      found that (1) lesion of SmI obviously attenuated the inhibitory effect of EA
      applied at "Zusanli" and "Huantiao" points on nociceptive responses in Pfneurons;
      (2) after lesion of SmI iontophoretic application of ACh markedly suppressed the
      nociceptive responses of Pf neurons, which was significantly different from the
      effect of iontophoretic NaCl (as the control) showing no influence on them; (3)
      the inhibition induced by iontophoretic ACh applied in the rats with lesion of
      SmI was similar to that produced by EA applied in those with SmI intact. It is
      indicated that EA can activate SmI to release ACh to exert descending modulation,
      in which ACh is involved in SmI originating descending regulation of Pf neruons
      in acupuncture analgesia.

PMID- 7648695
TI  - [Effect of electroacupuncture on the discharges of pain-sensitive neurons in the
      hypothalamic dorsomedial nucleus of rats].
AB  - The discharges of pain-sensitive neurons of the hypothalamic dorsomedial nucleus
      (DMH) in Sprague-Dawley rats were recorded with glass microelectrodes, After
      electroacupuncture acupoints "Zusanli" and "Sanyinjiao", the rate of spontaneous
      discharges and the rate and duration of the pain-evoked discharges of pain
      excitatory units of DMH were profoundly decreased, and the spontaneous firing
      rate of pain-inhibitory units was increased while their inhibitory response to
      nociceptive stimulation was released by the electroacupuncture. The results
      mentioned above suggest that DMH participates in the activity of acupuncture
      analgesia.

PMID- 7648696
TI  - [The analgesic extensiveness and specificity of EA at different points on
      nociceptive response of trigeminal convergent neurons (TCN)].
AB  - Our privious work have demonstrated that eletroacupuncture (EA) at acupoints
      seemed to have no specific effects. The present work is to observe whether the
      analgesic extensiveness and specificity of EA at points is related to EA
      intensity and the sites of points. Experiments were carried out on rats
      anaesthetized with Urathane. The spontaneous discharges and nociceptive responses
      of convergent neurons on right trigeminal dorsl horn to noxious stimulation at
      receptive field (cheek) were recorded extracellarly with glass micro-electrode.
      EA was applied at ipsilateral "Xiaguan" (on face) or "Zusanli" (on shank) point
      with low (2V) and high (18V) intensity. The nociceptive response of TCN could be
      inhibited by low intensity EA applied at "Xiaguan" but not "Zusanli", showing the
      specificity of points. High intensity EA at either "Xiaguan" or "Zusanli" also
      reduced the responses, showing the analgesic extensiveness of points. We suggest
      that "the gate of control" mechanism plays an important role in low intensity EA
      and "DNIC" mechanism does so in high intensity EA. The results suggest that we
      must pay attention to the manipulation and the intensity of acupuncture in the
      clinic work.

PMID- 7648697
TI  - [Change of the guaning nucleotide-regulating protein in substantia gelatinosa of
      spinal cord of rats after unilateral transection of dorsal roots and
      electroacupuncture: an immunohistochemical observation].
AB  - The Subunit alpha o of guanine nucleotide-binding protein (rabbit polyclonal
      antiserum 9120, K,J. Chang. USA), in the areas of rat spinal cord was localized
      by immunohistochemical PAP methods, and the changes of alpha o-immunoreactivity
      (alpha o-IR) in the substantia gelatinosa (SG) were observed after unilateral
      transection of dorsal roots and electroacupuncture. Intense alpha o-IR was
      presented in Rexed lamina I to III of the dorsal horn, and the highest alpha o-IR
      in lamina (SG), which was found than that in the normal and control animals.
      Iateral spinal nucleus of rat revealed higher density of alpha o-IR containing
      fiber networks. Following unilateral transection of dorsal roots and pain
      threshold increased significantly after electroacupuncture applied at the point
      "Huantiao", alpha o-IR was markedly decreased than that in the normal and control
      group in those areas. The optic density (OD) of alpha o-IR were measured, which
      decreased more markedly in opration and electroacupuncture group than that normal
      and control group. The results mentioned above indicate that Go-protein in
      terminals of primary nociceptive neurons of SG decreases markedly after dorsal
      roots transected and electroacupuncture. It was inferenced that partial Go
      protein probably originates from the primary sensory neurons, and the release of
      "inhibitory" of Go may increase (with weaker alpha o-IR). In a work, Go might
      play important roles on the primary afferents informational regulation and
      electroacupuncture analgesia of the regulation.

PMID- 7648698
TI  - [Time course of the effect of electroacupuncture on immunomodulation of normal
      rat].
AB  - Lymphocyte proliferation of splenocytes induced by concanavalin A (Con A) and the
      induction of IL-2 production test were used to study the effects of acupuncture
      on immunomodulation by stimulation of Zusanli (ST 36) and Lanwei (Extra 33)
      points of the rat's left leg. It was observed that the lymphocyte proliferation
      of splenocytes was increased in EA groups of 3 days (p < 0.05) 5 days (p < 0.001)
      and 7 days (P < 0.05). The parabolical curve could be found by currilinear
      regression (R2 = 0.9901). EA groups of 3 days and 5 days had a significantly
      increased induction of IL-2 production (P < 0.05). These results will be helpful
      to choose an optimal time for clinical treatment.

PMID- 7648699
TI  - [The role of sympathetic mechanism in the effect of electroacupuncture on
      immunoregulation].
AB  - 1. In normal control mice (only injected SRBC) after EA the lymphocyte
      transformation test (LTT, P < 0.05) and interlukin-2 (IL-2) activity (P < 0.05)
      were significantly increased, but the serum lysozyme (IZM, P < 0.01) was
      apparantly decreased. 2. After injection of 6-OHDA in mice, the spleen weight,
      spleen index, thymus weight, thymusindex, spleen lymphocyte population and serum
      IZM, igG contents were markedly decreased, whereas LTT, IL-2 and plaque forming
      cell (PFC) were umchanged, In contrast, the thymus lymphocyte population was
      markedly increased. 3. After EA of mice axotomized sympathetic nerve with 6-OHDA
      the above mentioned immune parameters deceased by 6-OHDA could be returned to
      normal or nearing normal levels. However, the unchanged LTT, IL-2 and the
      increased thymus lymphocyte population could be enhanced further, especially IL
      2. These results suggest that peripheral sympathetic nerve may be participation
      in the EA-mediating immunological responses.

PMID- 7648700
TI  - [An observation of protective effect of acupuncture on the cardiac function and
      anti-hemorrhagic shock].
AB  - This paper reports the study of the effect of the cardiac function and arterial
      pressure on rabbits with hemorrhagic shock by electroacupuncture Neiguan point.
      The result showed that PEP was shortened, ET was lengthened, SV, CO and Map were
      raised by needling Neiguan and the each index was significant difference (P <
      0.001). Above results indicated that needling may strengthen myocardial
      contractile force, protect the cardial pump function, raise the blood pressure,
      play a positive role during anti-hemorrhagic shock.

PMID- 7648701
TI  - [Influence of stimulating zusanli with moxibustion of different quality and
      quantity on gastrointestinal motor function of reserpinized rats].
AB  - This article is focused on the observation of changes in body temperature, body
      weight, cholinesterase activity in blood, and gastrointestinal motility of
      reserpinized rats treated by stimulating Zusanli (ST 36) with moxibustion of
      different quality. (mugwort floss or pipe tobacco) and quantity (strong
      stimulation or weak stimulation). The experiment shows that better results are
      achieved with moxibustion not by burning tobacco; the result of strong
      stimulation with moxa-sticks is better than that of weak stimulation with the
      same material. Strong stimulation with moxa-sticks can obviously increase the
      activity of cholinesterase (P < 0.05), inhibit hyperactive gastrointestinal
      motility (P < 0.05), maintain normal body temperature (P < 0.05), and prevent
      body weight lossing. All these show that therapeutic results of moxibustion are
      closely related to the quality and quantity of moxibustion.

PMID- 7648702
TI  - [The analysis of the mechanisms of both the SM and the extrapyramidal system
      modulating the nociceptive responses of the neurons in NRM].
AB  - The experiment was carried out on rats. Unit discharges of NRM were recorded
      extracellularly with glass microelectrode. Before the lesion of the head of N.
      Caudatus, 15 NRM neurons were recorded. The stimulation of the hindlimb areas of
      SM could obviously activate NRM neurons, the spontaneous discharges were
      increased to 59.06 +/- 25.35% (P < 0.05) and the nociceptive responses were
      obviously inhibited to -46.61 +/- 14.78 (P < 0.01) at 0 minute after stopping
      stimulation. Both effects lasted for 15 minutes, and then gradually returned to
      original level. After the lesion of the head of N. Caudatus, the effects of the
      stimulation of the hindlimb areas of SM on 19 NRM neurons were clearly decreased.
      The spontaneous discharges were increased to only 6.9 +/- 21.46% and the
      nociceptive responses were inhibited only -4.57 +/- 11.08% at 0 minute after
      stopping stimulation, even the nociceptive responses were slightly increased in 5
      30 minutes. The difference between the two groups was statistical significance.
      The value of the difference was about 42% (P < 0.05) at 0 minute and lasted 30
      minutes. It suggests that the effects of stimulating SM on NRM may be transmitted
      by the head of N. Caudatus in the extrapyramidal system.

PMID- 7648703
TI  - [The relation of the relative specificity of point to channel lines or spinal
      segments].
AB  - This work is to study whut the analgesia of EA is related with specificity of
      channel point or innervation of point. The discharges of 28 NRM neurons and their
      nociceptive responses induced by stimulation of dental pulp or tail tip in rats
      were recorded. The effects of EA of "Shangguan" and "Yanglingquan" of gall
      bladder channel of foot shaoyang on NRM neurons and their nociceptive responses
      were compared. and with that of "Xiaguan" and "Zusanli" of the stomach channel of
      foot Yangming. "Shangguan" and "Xiaguan" were located in the depressions at the
      upper and lower border of zygomatic arch respectively, and innervated by the n.
      trigeminus. The hind leg points "Yanglingquan" is located in the depression
      anterior and inferior to capitulum fibulae above "Zusanli" and both were
      innervated by n. peroneus communis. The results showed that EA of "Shangguan" or
      "Xiaguan" could activate NRM, increasing unit discharges about 70-120% for 10-15
      minutes (P < 0.05-0.001) and inhibit both nociceptive responses, but the
      inhibition on the nociceptive response induced by dental pulp (about -60% for 5
      10 minutes, P < 0.05-0.001) was stronger than that by tail tip (no effect or
      about -30% occasionally). "Yanglingquan" or "Zusanli" EA could also activate NRM
      and inhibit the nociceptive responses, but the inhibition on the nociceptive
      response of tail stimulation about -60-(-)40% for 30 minutes, P < 0.05-0.001) was
      stronger and longer than that of dental pulp (about -40% for 5-10 minutes, P <
      0.05-0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7648704
TI  - [Dynamic observation on the changes in capacity of gastric antrum under needling
      different acupoints of foot yangming meridian in human body].

PMID- 7648705
TI  - Beneficial effects of tumour necrosis factor-alpha (TNF-alpha) blockade in
      rheumatoid arthritis (RA)
AB  - The biological properties of TNF-alpha make it a candidate therapeutic target in
      RA. Our studies have demonstrated that TNF-alpha and its receptors are up
      regulated and co-expressed in the synovium and cartilage-pannus junction of RA
      joints. Neutralizing TNF-alpha antibodies reduce the production of the many pro
      inflammatory cytokines, including IL-1 and granulocyte-macrophage colony
      stimulating factor (GM-CSF), produced by mononuclear cells from RA in culture.
      When injected into DBA/1 mice with collagen-induced arthritis and TNF-alpha
      transgenic mice with arthritis, anti-TNF MoAbs decrease inflammatory damage of
      joints. Clinical trials employing cA2, a chimaeric anti-TNF-alpha MoAb, in open
      label and randomized placebo-controlled studies have demonstrated a dose
      dependent efficacy with impressive improvement in disease activity and acute
      phase responses lasting several weeks. We conclude that TNF-alpha is a critical
      mediator of inflammation in RA, and is an important therapeutic target in this
      disease.

PMID- 7648706
TI  - T cell receptor (TCR) V gene usage in patients with systemic necrotizing
      vasculitis.
AB  - Wegener's granulomatosis (WG) and polyarteritis nodosa (PAN) are systemic
      necrotizing vasculitides of unknown etiology. These disorders run a fatal course
      if untreated. T lymphocytes are implicated in the pathogenesis of WG, since they
      have been found to infiltrate affected organs, and sIL-2R correlates with disease
      activity. To elucidate further the role of T cells in necrotizing vasculitis, we
      have used a panel of 12 TCR V-specific MoAbs to investigate the number of cells
      expressing certain V alpha and V beta gene segments in the CD4+ and CD8+ subsets
      of altogether 11 patients with WG or PAN. In the group of patients, we found
      abnormal expansions of T cells using particular TCR V alpha or V beta gene
      products. These T cell expansions were more numerous, of a dramatically higher
      magnitude, and frequently more often found in the CD4 subset, compared with T
      cell expansions identified in healthy individuals. In long-term studies of the T
      cell expansions for up to 18 months, a heterogeneous pattern was revealed, with
      no obvious correlation to clinical features such as disease activity or
      treatment. Studies of TCR V gene usage in this group of patients may help in
      understanding the pathogenesis of necrotizing vasculitis, and in the
      identification of unknown antigens, and may open the possibility to a highly
      selective immunotherapy by targeting disease-mediating T cells.

PMID- 7648707
TI  - Activation of granulocytes by anti-neutrophil cytoplasmic antibodies (ANCA) in
      Wegener's granulomatosis: a predominant role for the IgG3 subclass of ANCA.
AB  - To study ANCA-induced granulocyte activation in relation to disease activity in
      Wegener's granulomatosis (WG), serum samples taken from patients with WG at the
      time of active (n = 17) and inactive (n = 17) disease were analysed for their
      capacity to activate primed normal donor granulocytes. Compared with control sera
      (n = 6), the capacity of IgG fractions from patients with WG to induce the
      respiratory burst was significantly higher (P < 0.0001). Furthermore, the
      capacity to induce the respiratory burst significantly correlated with ANCA titre
      (r = 0.499, P = 0.003). IgG fractions from patients with active extensive disease
      induced the respiratory burst significantly more strongly than IgG fractions from
      patients with limited disease (n = 7) (P < 0.01) or patients during disease
      remission (n = 17) (P < 0.001). As ANCA-induced neutrophil activation is Fc
      dependent and different IgG subclasses are involved in the interaction with
      various Fc receptors from neutrophils, we assessed changes in ANCA titre, total
      IgG and IgG subclass distribution of ANCA during active disease and remission in
      relation to the neutrophil-activating capacity of ANCA. Changes in capacity to
      activate granulocytes were related neither to changes in titre nor to changes in
      levels of total IgG, IgG1, IgG3, or IgG4 subclass of ANCA. However, changes in
      capacity to induce the respiratory burst were significantly related to changes in
      the relative amount of the IgG3 subclass of ANCA (P < 0.001), and not to changes
      in the relative amount of IgG1 or IgG4 subclass of ANCA. These data suggest that
      the increase in neutrophil-activating capacity of ANCA from inactive to active
      disease is, at least in part, based on the relative increase of the IgG3 subclass
      of ANCA that occurs during active disease.

PMID- 7648708
TI  - Serum 27E10 antigen: a new potential marker for staging HIV disease.
AB  - MRP8 and MRP14 are myeloic related proteins expressed by most circulating and
      emigrated neutrophils and monocytes. Their composite molecule MRP8/14 (27E10
      antigen) was shown to exhibit striking antimicrobial properties. The aim of the
      present study was to assess the value of MRPs as markers for detection of the
      different stages of HIV infection (Centres for Disease Control and Prevention,
      1993). By employing the ELISA technique we measured serum concentrations of these
      proteins in samples from 122 HIV patients at the various stages of disease, and
      the results were compared with those for healthy controls. Serum levels of the
      heterodimeric molecule 27E10 were significantly increased (P < 0.001) in patients
      with CDC stages II and III, with the highest levels being in patients with stage
      III and acute ongoing opportunistic infections. For the single component MRP14,
      significantly raised levels (P < 0.05) were only found in HIV stage III
      individuals with acute clinical events. Similar associations were not found for
      MRP8 alone. Increase was not related to CD4+ cell count. There was a significant
      correlation between 27E10 antigen serum concentrations and levels of neopterin in
      patients with HIV stages II and III without acute concurrent illness. Patients
      being treated with Zidovudine showed no statistically significant variation in
      levels of 27E10 and its single components MRP8 and MRP14 compared with untreated
      patients. These findings suggest that elevation of MRP14 levels occurs in HIV+
      individuals at later stages post-HIV infection, after the onset of opportunistic
      infections. 27E10 antigen is concluded to be a potential marker for the different
      stages of HIV disease.

PMID- 7648709
TI  - Circulating immune complexes and analysis of renal immune deposits in feline
      immunodeficiency virus-infected cats.
AB  - Total immunoglobulin content and concentration of immune complexes (IC) were
      determined in the sera of 51 cats infected with feline immunodeficiency virus
      (FIV) and of 40 controls. IgG and IgM were quantified by radial immunodiffusion
      and circulating IC (CIC) by the CIC-conglutinin assay. IgG fractions were
      obtained by acid elution from kidney tissues of 15 FIV-infected and five negative
      control cats to investigate the possible role of IC in the genesis of renal
      damage observed in infected animals. Mean concentrations of IgG and circulating
      IC were higher in FIV-infected cats than in controls (29.6 +/- 6.7 versus 23.0 +/
      1.9 mg/dl (mean +/- s.d.) P < 0.001; and 66.5 +/- 17.0 versus 27.4 +/- 19.9% I,
      P < 0.001, respectively), while IgM levels were only slightly increased (0.9 +/-
      0.05 versus 0.87 +/- 0.04 mg/dl, P < 0.02). Immunoglobulin fractions were eluted
      from 10 of the 15 renal tissue samples from FIV-infected cats and were found to
      be polyclonal and at least partly specific for FIV antigens. These findings
      confirm the presence of a B cell activation in FIV-infected cats and demonstrate
      the presence of high levels of CIC in their sera. The presence of immune deposits
      in renal tissues suggests that IC might play a role in the pathogenesis of the
      renal damage observed in FIV-infected cats.

PMID- 7648710
TI  - Glucocorticoid-mediated immunomodulation: hydrocortisone enhances
      immunosuppressive endogenous retroviral protein (p15E) expression in mouse immune
      cells.
AB  - To define glucocorticoid (GC)-regulated genes contributing to the anti
      inflammatory and immunosuppressive effects of GC, previous work from our
      laboratory revealed up-regulation of transcripts from endogenous type B mouse
      mammary tumour virus (Mtv) and type C murine leukaemia virus (Emv) loci by high
      dose GC treatment of P388D1 macrophage-like cells. This study demonstrates
      enhancement of expression from Mtv and Emv loci in P388D1 cells by more
      physiological hydrocortisone concentrations (1 microM), and shows direct
      transcriptional mode of regulation by blocking GC-mediated signal transduction at
      different levels. Furthermore, we found up-regulation of Emv mRNA steady-state
      levels in murine lymphoid lineage cells (T-like EL4 and BW5147 cells; B-like X63
      cells) upon GC treatment. The Emv transcripts shown by us to be GC-up-regulated
      encode for the transmembrane envelope protein TM/p15E which is highly conserved
      in several retroviruses. TM/p15E and the p15E-like products found in humans exert
      immunosuppressive effects in different test systems. Thus, our findings raise the
      possibility that immunomodulation by GC might be mediated in part by enhanced
      expression of p15E(-like) products.

PMID- 7648711
TI  - The association of complement activation at a low temperature with hepatitis C
      virus infection in comparison with cryoglobulin.
AB  - Complement activation at a low temperature in vitro and cryoglobulinaemia are
      associated with hepatitis C virus (HCV) infection. The frequency of HCV antibody
      positivity determined in serum specimens that showed the cold-dependent
      activation of complement was 100%, whereas it was 48% among sera with
      cryoglobulin. On the other hand, the frequency of cold activation among HCV
      infected sera was 41%, and that of cryoglobulin 48%. Cold activation was not
      found in any HCV- sera studied, whereas cryoglobulin was found at a frequency of
      14% in HCV- sera. Cold activation was also absent among hepatitis B virus (HBV) S
      antigen or antibody-positive sera, except a few that were both HBV+ and HCV+.
      Rheumatoid factor was also frequently detected in sera with cold activation or
      cryoglobulin. Cold activation and cryoglobulin may be generated by common
      mechanisms in which a low avidity, low temperature-preferring antibody may
      function. In sera with cold activation, fine particles of immune complexes, which
      do not form precipitates, may activate the complement system. HCV is a unique
      virus that coexists with antibody in the serum, therefore the avidity of the
      antibody for the virus antigen may be low, and occasionally react only at a low
      temperature. This may be why the in vitro phenomenon related to immune complexes
      occurs specifically in HCV-infected sera.

PMID- 7648712
TI  - Avidity of antibody responses to Actinobacillus actinomycetemcomitans in
      periodontitis.
AB  - We designed a study to examine the serum IgG antibody avidity characteristics in:
      (i) normal subjects (N); (ii) Actinobacillus actinomycetemcomitans-infected adult
      periodontitis (AP Aa+); (iii) A. actinomycetemcomitans-infected localized
      juvenile periodontitis (LJP Aa+); and (iv) AP subjects (AP) with various antibody
      patterns and disease presentation. Although there were significant elevations in
      antibody levels for AP Aa+ and LJP Aa+ patients compared with AP and normal
      patients (P < 0.0001), there were no significant differences in the avidity
      indices (AI). Correlations of antibody levels to avidity revealed that functional
      activity of the antibody as measured by avidity was independent of antibody
      levels. Increasing antibody levels correlated with an increase in the number of
      infected sites, yet there was a trend for A1 to decrease with increased
      infection. Avidity indices for all patient groups did not appear to show a strong
      biologic relationship to plaque; however, in AP Aa+ and LJP Aa+ patients there
      was a generally positive relationship between avidity and bleeding on probing or
      pocket depth. In AP Aa+ and LJP Aa+ patients, and in AP patients there was a
      positive relationship of avidity through a threshold of approximately 8 active
      disease sites. This study hypothesized that antibody avidity to A.
      actinomycetemcomitans could help to explain the relationship between the active
      host response and chronic infection with this pathogen. The results provide
      evidence that both antibody levels and avidity may contribute to the variation in
      host resistance to infection and disease associated with A.
      actinomycetemcomitans.

PMID- 7648713
TI  - Changes in cytokine and nitric oxide secretion by rat alveolar macrophages after
      oral administration of bacterial extracts.
AB  - Oral administration of the bacterial immunomodulator Broncho-Vaxom (OM-85), a
      lysate of eight bacteria strains commonly causing respiratory disease, has been
      shown to enhance the host defence of the respiratory tract. In this study we
      examined the effect of orally administered (in vivo) OM-85 on stimulus-induced
      cytokine and nitric oxide secretion by rat alveolar macrophages in vitro. The
      results show that alveolar macrophages isolated from OM-85-treated rats secreted
      significantly more nitric oxide, tumour necrosis factor-alpha (TNF-alpha) and IL
      1 beta upon in vitro stimulation with lipopolysaccharide (LPS), whereas, in
      contrast, LPS-induced IL-6 secretion was significantly lower. The observed
      effects of in vivo OM-85 treatment on stimulus-induced cytokine secretion in
      vitro are not due to a direct effect of OM-85 on the cells, because in vitro
      incubation of alveolar macrophages with OM-85 did not result in altered activity,
      nor did direct intratracheal instillation of OM-85 in the lungs of rats result in
      altered alveolar macrophage activity in vitro. It is hypothesized that oral
      administration of OM-85 leads to priming of alveolar macrophages in such a way
      that immune responses are non-specifically enhanced upon stimulation. The
      therapeutic action of OM-85 may therefore result from an enhanced clearance of
      infectious bacteria from the respiratory tract due to increased alveolar
      macrophage activity.

PMID- 7648714
TI  - Tumour necrosis factor-alpha (TNF-alpha) in the host resistance to mycobacteria
      of distinct virulence.
AB  - The relative virulence of different isolates of Mycobacterium avium has been
      linked to their capacity to trigger the secretion of TNF from the macrophages
      they infect. Smooth opaque (SmOp) variants of Myco. avium have been shown to
      trigger higher expression of TNF-alpha by macrophages in vitro than the smooth
      transparent (SmTr) variants. To analyse the role of TNF in resistance to
      infection by Myco. avium, we studied the infection by two different morphotypes
      of strain 2.151 of Myco. avium both in vitro and in vivo in the presence or
      absence of neutralizing antibodies to TNF. No effects were found in vitro
      regarding the growth of either isolate of Myco. avium. In vivo, only the virulent
      SmTr morphotype showed enhanced growth in the presence of the neutralizing
      antibodies. This enhancement occurred relatively late when priming for TNF
      secretion in vivo was evident. Among four isolates of Myco. avium, three virulent
      ones induced a marked priming for TNF release and one avirulent strain did not.
      Mycobacterium tuberculosis H37Ra, which is very active in inducing TNF release
      due to its lipoarabinomannan moiety, was used to compare with the previous
      results. The growth of H37Ra in macrophages was increased in vitro by the
      neutralization of TNF and neutralization of either TNF and/or interferon-gamma
      (IFN-gamma) enhanced the in vivo proliferation of this microbe in the spleen and
      liver of infected animals, whereas only the combination of both anti-TNF and anti
      IFN-gamma enhanced bacterial proliferation in the lung. We conclude that
      resistance to the avirulent strains of Myco. avium did not involve TNF, but
      rather antimicrobial mechanisms expressed constitutively in the mononuclear
      phagocytes. In contrast, TNF plays an important role in the control of Myco.
      tuberculosis H37Ra infection.

PMID- 7648715
TI  - Differential correlation between interleukin patterns in disseminated and chronic
      human paracoccidioidomycosis.
AB  - In an attempt to understand better the immunoregulatory disorders in
      paracoccidioidomycosis (PCM), the possible correlation between interleukin
      pattern, lymphoproliferation, C-reactive protein (CRP) and specific antibody
      levels was investigated in the polarized clinical forms of this disease. We
      studied 16 PCM patients, eight with the disseminated disease (four under
      treatment and four non-treated) and eight with the chronic disease. The patients
      with disseminated disease exhibited high antibody titres specific to
      Paracoccidioides brasiliensis antigen compared with patients with the chronic
      form of disease. Tumour necrosis factor (TNF), IL-1, IL-6 and CRP in the serum of
      non-treated disseminated PCM patients were increased, which correlated positively
      with the low mitogenic response of peripheral blood mononuclear cells (PBMC) to
      phytohaemagglutinin (PHA) (P < 0.01) and with the high antibody titres (P <
      0.001) of these patients. Moreover, we found in the disseminated PCM patients
      positive correlations between IL-1 and IL-6 (P = 0.0007); IL-1 and TNF (P =
      0.0045); IL-1 and IL-6 with the high antibody titres (P = 0.0834 and P = 0.0631,
      respectively); IL-1, IL-6 and TNF with CRP levels. By contrast, no correlations
      were found with those interleukins in the treated disseminated and chronic
      patients or in controls. It was interesting to find an inverse correlation
      between IL-4 and antibody production in non-treated disseminated PCM (r = 
      0.4770); moreover, a significant correlation (P = 0.0820) was found in chronic
      PCM patients with respect to the low level of either IL-4 and antibody titres
      against fungus antigen. Chronic PCM patients also had IL-2 levels inversely
      correlated with antibody production (r = -0.6313; P = 0.0628). Inverse
      correlations were also observed between IL-2 and IL-6 levels in non-treated
      disseminated patients (P = 0.0501) and between IL-2 and IL-4 in chronic patients
      (P = 0.0131). The inflammatory cytokines might have a pivotal role in the genesis
      and in control of some aspects of the disease, such as granulomatous reaction,
      hypergammaglobulinaemia and depression of T cell-mediated immunity in PCM.

PMID- 7648716
TI  - The role of somatic structure of the fungus Paracoccidioides brasiliensis upon B
      cell activation in experimental paracoccidioidomycosis.
AB  - In this study, we report an increase of the number of antibody-secreting cells
      and the augmentation of antibody production against unrelated antigens in mice
      infected with the fungus P. brasiliensis, as well as in mice inoculated with cell
      wall preparation isolated from P. brasiliensis (CW). The immunomodulatory effect
      of the live fungus and the CW preparation was dose-dependent, and their actions
      were mainly restricted to the i.v. or i.p. inoculation simultaneously with the
      sheep erythrocyte challenge by the i.v. route or restricted to i.p. inoculation
      of CW when bovine serum albumin (BSA) antigen was used. The dependence of
      antibody production on different routes of CW inoculation was correlated with the
      number of antigen-specific B cells in the spleen as determined by direct and
      reverse plaque-forming cell assays. The immunization schedules using CW
      preparation caused a preferential production of IgM and IgG3 antibodies. The
      results also showed that the hyperactive humoral immune response of mice induced
      by i.p. inoculation of CW was devoid of polyclonal B cell activation compared
      with the effects observed for the lipopolysaccharide (LPS)-treated groups.
      Paracoccidioides brasiliensis CW components may have potent immunological
      properties related to the non-specific B cell activation found in
      paracoccidioidomycosis.

PMID- 7648717
TI  - Comparison of two types of intravenous immunoglobulins in the treatment of
      neonatal sepsis.
AB  - In a prospective double-blind study, standard intravenous immunoglobulin (IVIG)
      was compared with an IgM-enriched IVIG in the treatment of neonatal sepsis. The
      two treatment groups were also compared with matched controls. One hundred and
      thirty babies (65 in each group) ranging from 0 to 24 days old, 480 to 4200 g in
      weight and born between 24 and 42 weeks of gestation who had, or were suspected
      of having, sepsis were given either standard IVIG or IgM-enriched IVIG (250 mg/kg
      per day) for 4 days in addition to supportive and antibiotic therapy. A further
      65 babies who received similar supportive, antibiotic and fluids but not IVIG
      were used as matched controls. Mortality from infection in 'culture proven
      sepsis' was 3/44 (6.8%) in the IgM-enriched IVIG group, 6/42 (14.2%) in the
      standard IVIG group, and 11/43 (25.5%) in the control group (P = 0.017, IgM
      versus control, P = 0.19 standard IVIG versus control). There was no statistical
      difference in the outcome between the two immunoglobulin therapy groups (P =
      0.25). The study indicates that IVIG improves outcome in neonatal sepsis when
      used as an adjunct to supportive and antibiotic therapy, but larger studies are
      required to confirm this.

PMID- 7648718
TI  - Fibronectin (FN) decreases glomerular lesions and synthesis of tumour necrosis
      factor-alpha (TNF-alpha), platelet-activating factor (PAF) and FN in
      proliferative glomerulonephritis.
AB  - We have studied the effect of therapy with plasma FN on glomerular synthesis of
      PAF, TNF-alpha and FN, in experimental proliferative glomerulonephritis.
      Glomerular PAF, TNF-alpha and FN production were increased in rats with
      nephritis. Peak glomerular PAF production preceded, while peak glomerular TNF
      alpha bioactivity coincided with maximal proteinuria. Rats treated with FN (5
      mg/kg per 48 h) for 15 days had less proteinuria, glomerular and interstitial
      cell infiltration and glomerular PAF, TNF-alpha and FN synthesis than non-treated
      rats. In order to characterize further the mechanisms of action of FN, healthy
      rats were injected with either FN or saline. Peripheral blood mononuclear cells
      and neutrophils from healthy rats injected with FN secreted less TNF-alpha and
      PAF, respectively, than those obtained from saline-treated rats. Our data suggest
      that the beneficial effect of FN may be related to decreased number of glomerular
      leucocytes and decreased synthesis of inflammatory mediators and extracellular
      matrix.

PMID- 7648719
TI  - Strain variation in susceptibility to the development of monoclonal antibody 5-1
      6-induced proteinuria in rats.
AB  - Susceptibility to the development of MoAb 5-1-6-induced proteinuria was
      investigated in four different rat strains, i.e. Brown-Norway (BN), Lewis (LEW),
      Sprague-Dawley (SD) and Wistar. An intravenous injection of 5 mg of MoAb 5-1-6 to
      female 7-week-old rats of a given strain induced massive proteinuria in BN, LEW
      and Wistar rats. However, SD rats developed almost no proteinuria. A similar
      tendency was observed in the second experiment, in which the injected dose of
      MoAb was adjusted according to the body weight of each rat (3 mg/100 g body
      weight). Immunofluorescence (IF) and immunoelectron microscopy (IEM) revealed no
      differences between the binding patterns of the MoAbs to normal rat kidneys
      derived from each strain. Quantitative study using 125I-labelled MoAb showed that
      there was no significant difference in the amount of antibody bound to the kidney
      1 h and 5 days after injection between two rat strains, LEW and SD. Localization
      of 5-1-6 in vivo and its kinetics were investigated. In IF a linear-like pattern
      along capillary walls was observed 2 h after injection in both LEW and SD
      strains. This linear-like pattern was shifted to a granular pattern in
      proteinuric LEW rats 6 days after injection, whereas it remained linear-like in
      non-proteinuric SD rats. IEM confirmed this difference in the localization of
      injected MoAb 6 days after injection to LEW and SD rats also at the
      ultrastructural level. We conclude that there is a clear-cut strain difference in
      the development of proteinuria induced by MoAb 5-1-6. SD rats were less
      susceptible to MoAb-induced glomerular injury than BN, LEW and Wistar rats.
      Although the exact reason for strain variation in susceptibility to MoAb-induced
      proteinuria remains to be clarified, the movement of bound MoAb, presumably
      together with corresponding antigenic molecule along the glomerular epithelial
      cell surface followed by endocytosis into the epithelial cell, seems to be
      closely related to the induction of proteinuria.

PMID- 7648720
TI  - Anti-CD11b/CD18 antibodies reduce inflammation in acute colitis in rats.
AB  - The influx of monocytes and neutrophils into the inflamed tissue could be an
      important aspect in the pathogenesis of inflammatory bowel disease (IBD). A
      membrane protein involved in the monocyte/neutrophil adherence to endothelium is
      CD11b/CD18 or alpha M beta 2 (complement receptor type 3 = CR3). In the present
      study the role of CD11b/CD18 in experimental IBD was studied by treatment with
      ED7 and OX42, two MoAbs against CD11b/CD18. Colitis was induced in rats by a
      single, rectal administration of 30 mg 2,4,6-trinitrobenzene sulfonic acid (TNBS)
      dissolved in ethanol 30%. Two hours before and 3 days after induction of colitis,
      the animals were given an i.v. dose of 0.5 mg of either ED7 or OX42 in 1 ml PBS.
      Controls received PBS or an irrelevant MoAb. Four days after the last treatment
      with the antibodies, the rats were killed, and macroscopic damage scores of the
      colon were determined. Macrophages and granulocytes were studied by
      immunohistochemistry and quantified by Interaktives Bild Analysen System (IBAS),
      and myeloperoxidase (MPO) activity in colonic tissue was measured. After
      treatment with ED7 and OX42 the mean damage score of the colon was reduced from
      4.2 in IBD animals to 1.0 and 1.3, respectively. Smaller areas of ulcerations and
      a decrease in the number of ulcerations were observed compared with PBS-treated
      rats. Furthermore, the amount of infiltrating monocytes and leucocytes in the
      submucosa was enormously reduced, as well as MPO activity in the colonic tissue.
      These results show that treatment with MoAbs against CD11b/CD18 reduces clinical
      signs of experimental IBD in rats by a partial blockade of infiltrating
      macrophages and granulocytes.

PMID- 7648721
TI  - Increased lipopolysaccharide-induced tumour necrosis factor levels and death in
      hypercholesterolaemic rabbits.
AB  - Nutritional-induced hypercholesterolaemia in New Zealand rabbits causes increased
      susceptibility to experimental infections. Rabbits fed cholesterol (0.5 g%) for 8
      weeks were injected intravenously with varying doses of Escherichia coli 0127: B8
      lipopolysaccharide (LPS; 3-100 micrograms/kg). The levels of cholesterol,
      triglycerides, tumour necrosis factor (TNF), and the survival rates of treated
      rabbits were then measured. Rabbits fed either normal chow or chow impregnated
      with sesame oil were used as controls. LPS induced higher serum TNF levels in
      hypercholesterolaemic rabbits than in normal rabbits or rabbits fed with chow
      containing sesame oil. TNF levels rose faster in hypercholesterolaemic rabbits
      than in normal rabbits, reaching maximum levels at 60 min and 120 min,
      respectively, after LPS injection. The survival rate of hypercholesterolaemic
      rabbits (1/11) was lower than in normal rabbits (6/7) or rabbits fed with the
      sesame oil chow (4/4) at the higher LPS doses. No death occurred at lower doses.
      One possible interpretation of these results, also supported by neutralization
      experiments, is that increased TNF secretion in hypercholesterolaemic rabbits
      raises the host's susceptibility to experimental endotoxaemia and possibly to
      Gram-negative infection.

PMID- 7648722
TI  - Human recombinant IL-4 decreases the emergence of non-specific cytolytic cells
      and favours the appearance of memory cells (CD4+CD45RO+) in the IL-2-driven
      development of cytotoxic T lymphocytes against autologous ovarian tumour cells.
AB  - As IL-4 and IL-6 have also been reported to promote the development of T
      lymphocytes such as IL-2, we investigated their role in the development of
      specific cytotoxic T lymphocytes (CTL) against autologous ovarian tumours in
      mixed lymphocyte tumour cultures (MLTC). Peripheral blood lymphocytes (PBL) from
      five ovarian carcinoma (OC) patients were incubated with autologous OC cells at a
      PBL:OC cell ratio of 20:1 in IL-2 alone (50 U/ml for the first week and 200 U/ml
      thereafter) or with IL-4 (100 U/ml) and/or IL-6 (5 U/ml). Neither IL-4 nor IL-6
      improved lymphocyte proliferation consistently. In contrast, IL-4 reduced
      significantly the development of LAK activity as assayed against Daudi cell line,
      and decreased modestly the emergence of natural killer (NK) activity as assayed
      against K562. This property was not shared by IL-6. The prevention of the
      development of non-specific cytolytic activity (LAK and NK activities) was much
      stronger when the MLTC was started with IL-4 in the absence of IL-2 during the
      first week in culture. A concomitant drop in NKH-1 expression (CD56) was
      observed. By inhibiting the emergence of non-specific cytotoxicity, IL-4 provided
      better evidence of the specific cytolytic activity directed at ovarian cells. In
      parallel, a significant increase in the generation of memory cells (CD4+CD45RO+)
      was observed with IL-4. In conclusion, in this model, IL-4 added before IL-2
      decreases significantly the emergence of non-specific cytotoxic cells, and
      promotes the generation of memory cells. These properties may be of interest in
      the design of strategies aimed at obtaining tumour-specific cells for
      investigational and immunotherapeutic purposes.

PMID- 7648725
TI  - Canadian Paediatric Society annual meeting. Montreal, Quebec, June 24-28, 1995.
      Abstracts.

PMID- 7648723
TI  - Interaction of the cell-binding domain of fibronectin with VLA-5 integrin induces
      monokine production in cultured human monocytes.
AB  - The effect of fibronectin on IL-1 alpha, IL-1 beta, tumour necrosis factor-alpha
      (TNF-alpha), and IL-6 production was investigated with cultured monocytes
      isolated from human peripheral blood. Monokine concentrations were determined by
      both ELISA and bioassay. Fibronectin markedly stimulated the secretion of IL-1
      alpha, IL-1 beta, TNF-alpha and IL-6 from cultured monocytes in a dose-dependent
      manner, with the maximal effect apparent within 24 h. Northern blot analysis
      revealed a marked increase in the abundance of mRNA specific for each monokine on
      exposure of monocytes to fibronectin. Monoclonal antibodies to the alpha chain of
      very late antigen (VLA)-5, the beta 1 integrin, the alpha chain of Mac-1, and the
      beta 2 integrin, as well as the synthetic peptide of GRGDSP (which corresponds to
      the cell-binding domain of fibronectin), inhibited (> 50%) fibronectin-induced
      monokine production. Monoclonal antibodies to the alpha chain of VLA-4, and the
      alpha chain of LFA-1, as well as the synthetic peptide CS-1 (which corresponds to
      the alternatively spliced connecting segment of fibronectin) and the control
      peptide GRADSP, had no inhibitory effect on monokine production. A MoAb, R60,
      that recognizes an epitope of the fibronectin molecule that includes the RGD
      sequence, inhibited monokine production, whereas the MoAb Y16, which recognizes
      another epitope of fibronectin not including RGD, did not. These results indicate
      that fibronectin-induced production of IL-1 alpha, IL-1 beta, TNF-alpha and IL-6
      from cultured monocytes is mediated predominantly by interaction of the cell
      binding domain of fibronectin with VLA-5, although Mac-1 also may contribute to
      this effect of fibronectin. Our results indicate that the interaction of
      fibronectin with integrins may contribute to the cytokine network in inflammatory
      response.

PMID- 7648726
TI  - Positive In-111 WBC scan in a patient with ischemic ileocolitis and negative
      colonoscopies.
AB  - Early ischemic bowel disease may be apparent on In-111 WBC scan before endoscopic
      changes of the mucosa. This may indicate a subacute process. The case in point
      did have angiographic findings of ileocolitis despite repeated colonoscopy.

PMID- 7648724
TI  - Both VH and VL chains of polyreactive IgM antibody are required for
      polyreactivity: expression of Fab in Escherichia coli.
AB  - Monoclonal polyreactive antibodies can bind to many structurally dissimilar self
      and non-self antigens. Neither the precise antigen-binding site on the
      polyreactive antibody molecule nor the molecular basis of polyreactivity has been
      elucidated. The present study was initiated to see whether antibody genes
      encoding the Fab fragment of a human monoclonal polyreactive IgM antibody (MoAb
      67) could be efficiently expressed in Escherichia coli, and whether the
      bacterially expressed Fab fragments possessed biological activity. cDNA encoding
      the variable domains of the heavy and light chains of MoAb 67 were cloned,
      amplified by polymerase chain reaction (PCR) and expressed in E. coli. Neither
      the recombinant heavy nor light chain showed antigen-binding activity. In
      contrast, the recombinant Fab 67 fragment showed the same antigen-binding
      reactivity profile as the native IgM antibody. It is concluded that the antigen
      binding activity of polyreactive antibodies resides in the Fab fragment, and that
      both the heavy and light chains are required for activity.

PMID- 7648727
TI  - Myocardial F-18 fluorodeoxyglucose imaging by SPECT.
AB  - F-18 fluorodeoxyglucose (FDG) in combination with positron emission tomography
      (PET) is used in patients with coronary artery disease to detect viable
      myocardium. It was shown that FDG PET is highly accurate in predicting
      reversibility of cardiac function after revascularization when viable tissue is
      present. Because PET centers are not widely available, the clinical use of FDG is
      limited. The authors have shown in another study that imaging 511 keV with planar
      scintigraphy and a special collimator is feasible. Furthermore, they have studied
      myocardial FDG uptake in normal volunteers and in patients with coronary artery
      disease using SPECT. Recently, they have studied the value of FDG SPECT to
      predict recovery of contractile function before revascularization in patients
      undergoing bypass surgery. It appears that the FDG SPECT approach is feasible and
      can predict reversibility of wall motion abnormalities. Further studies are
      needed to compare FDG SPECT with other techniques for the detection of viable
      myocardium.

PMID- 7648728
TI  - The value of bronchodilator administration in asthmatic patients before lung
      imaging.
AB  - A 17-year-old boy with chest pain and severe bronchospasm underwent lung imaging
      to exclude pulmonary embolism. This showed widespread nonsegmental defects in
      both the ventilation and perfusion scans. A repeat study performed immediately
      after nebulized bronchodilator administration was normal apart from changes
      consistent with left lower lobe pneumonia and atelectasis which had subsequently
      evolved on the chest radiograph. Bronchodilator administration is valuable in
      improving the accuracy of lung scanning in asthmatic patients by reducing the
      perfusion and ventilation abnormalities caused by hypoxia-induced
      vasoconstriction.

PMID- 7648729
TI  - Effects of inhalation of steroids on lung permeability in patients with asthma.
AB  - This study evaluated the effect of inhalation of steroids on lung permeability in
      patients with asthma by measuring the clearance of Tc-99m DTPA aerosol from the
      alveolar to vascular space. Twenty patients with asthma were studied in the
      supine position with a gamma camera and the clearance half time (T 1/2) was
      calculated. The base line lung permeability study was performed before treatment
      with inhalation of 100 micrograms beclomethasone dipropionate four times daily
      for 1 week, then the study was repeated. After treatment with inhalation of
      steroid, there was a change in T 1/2 from 76.4 +/- 37.4 minutes to 86.6 +/- 48.2
      minutes (P = 0.08). This preliminary study suggests that lung permeability is not
      altered by inhaled steroid therapy.

PMID- 7648730
TI  - Scintigraphic findings in renal malakoplakia.
AB  - The scintigraphic findings in a rare case of bilateral renal malakoplakia are
      presented. Markedly increased Ga-67 activity was present in both kidneys in sites
      corresponding to focal cortical defects on Tc-99m gluceptate (glucoheptonate)
      imaging. Interestingly, there was no abnormal renal activity with In-111
      leukocyte scanning.

PMID- 7648731
TI  - Tc-99m phytate bone marrow scintigraphy showing multiple areas of focal
      hyperactivity in a patient with lung cancer. A case report.
AB  - Focal hyperactivity indicative of metastases is a rare finding in bone marrow
      imaging. In a lung cancer patient with multiple bony metastases, the Tc-99m
      phytate bone marrow imaging revealed multiple focal areas of increased
      radioactivity corresponding to the bone scan findings. The findings presented are
      consistent with a previous animal study, which found that phytate distribution
      was similar to that of diphosphonate in the skeletal system of rats and rabbits.
      The authors conclude that Tc-99m phytate should not be used as a bone marrow
      imaging agent. Further studies of Tc-99m phytate bone marrow scintigraphy on
      human beings are under way.

PMID- 7648732
TI  - Metastatic soft tissue calcification in chronic renal failure detected by
      radionuclide imaging.
AB  - Metastatic calcification has been reported in several disease entities, including
      chronic renal failure. Various imaging modalities have been shown to be useful in
      the detection of metastatic soft tissue calcification. Radionuclide imaging may
      detect metastatic soft tissue calcification more readily than routine diagnostic
      modalities and be a valuable noninvasive method to establish an early diagnosis
      in high-risk patients. The authors report a patient with extensive soft tissue
      metastatic calcification who had a myriad of clinical symptoms. The extensive
      calcification was detected with a radionuclide imaging.

PMID- 7648733
TI  - In-111 octreotide scintigraphy in the diagnostic evaluation of en plaque
      meningioma. A case report.
AB  - A 44-year-old woman had a 13-year history of a small bulge of the left frontal
      region which had increased in size during the last year. At admission, an orange
      sized, hard, fixed left frontal mass was found. Magnetic resonance imaging showed
      hyperostosis in the left frontal region which was causing a skull deformity and
      marked focal meningeal enhancement. A hyperostotic plaque meningioma was
      hypothesized. In-111 octreotide scintigraphy confirmed the diagnosis before
      surgery. In-111 octreotide scintigraphy allows biologic characterization of
      neoplasms in vivo.

PMID- 7648734
TI  - Noninvasive diagnosis of Caroli syndrome associated with congenital hepatic
      fibrosis using hepatobiliary scintigraphy.
AB  - A patient who was studied for portal hypertension had an enlarged liver and
      multiple hepatic cysts on abdominal CT scan. He underwent hepatobiliary
      scintigraphy using Tc-99m mebrofenin which documented communication of the cysts
      with the main biliary tree and allowed a noninvasive diagnosis of Caroli syndrome
      associated with congenital hepatic fibrosis.

PMID- 7648735
TI  - Imaging of multiple bilateral parotid gland oncocytomas.
AB  - Oncocytoma of the salivary glands is a rare tumor that usually follows a benign
      course and, in most cases, can be cured by surgical resection. The authors report
      a rare case of multiple bilateral parotid oncocytomas that presented clinically
      with two palpable parotid masses. Both CT and MRI scans demonstrated multiple
      masses in each parotid gland. The tumors exhibited intense uptake and prolonged
      retention of Tc-99m pertechnetate. The diagnosis was confirmed by fine needle
      aspiration. Sialoscintigraphy is a simple and noninvasive procedure that can
      usually separate benign entities like Warthin tumor and oncocytoma of the
      salivary glands from malignant tumors, and significantly affect the course of
      treatment.

PMID- 7648737
TI  - Regional cerebral blood flow and metabolism in Sturge-Weber disease.
AB  - A 50-year-old man with Sturge-Weber syndrome (SWS) and left cerebral hemisphere
      atrophy was studied using PET with O-15 oxygen and O-15 water in order to
      evaluate regional cerebral blood flow and energy metabolism in this condition.
      PET demonstrated decreased perfusion and increased oxygen extraction fraction in
      the affected left cerebral hemisphere and ipsilateral cerebellum. These findings
      suggest that a chronic state of reduced perfusion may be the etiology for the
      cerebral hemiatrophy seen in some patients with SWS.

PMID- 7648736
TI  - Advanced fibrodysplasia ossificans progressiva.
AB  - Fibrodysplasia ossificans progressiva is a rare hereditary variant of
      heterotropic bone formation that is often difficult to diagnose. A bone scan of
      an advanced case of this condition is presented. Nuclear medicine physicians
      should be familiar with various aspects of this disease.

PMID- 7648738
TI  - Radionuclide imaging in extraskeletal myxoid chondrosarcoma.
AB  - The authors present a case of extraskeletal myxoid chondrosarcoma. The MR study
      clearly showed the extent of the tumor and a "rings and arcs" pattern appeared
      after Gadolinium-DTPA administration in the T1 weighted images. Dynamic Tc-99m
      MDP and Tc-99m DTPA scintigraphy showed increased blood flow in the mass. The
      delayed 3-hour images demonstrated moderate Tc-99m MDP uptake, but intense Tc-99m
      DTPA accumulation in the tumor. Surprisingly, the Ga-67 scan failed to
      demonstrate the tumor.

PMID- 7648739
TI  - Detection of malignant melanoma by Tc-99m HMPAO.
AB  - A number of radiopharmaceutical agents have been evaluated for the detection of
      malignant melanoma. Because anamine is necessary for melanin synthesis, melanotic
      tumors may possess numerous amine receptors. Tc-99m HMPAO consists of macrocyclic
      amine radicals. The purpose of this study was to evaluate Tc-99m HMPAO as an
      effective agent for localizing malignant melanomas on the radioisotope imaging.
      Six patients, with malignant melanomas were studied. Tc-99m HMPAO SPECT images
      were obtained in all patients. SPECT was used for the localization of the primary
      focus, and whole body scans were used for the evaluation of unexpected metastatic
      lesions. The results were compared with MRI and CT. Tc-99m HMPAO SPECT revealed a
      high correlation with CT and MRI for the primary focus. Abnormally increased
      activity at the unexpected metastatic lymph nodes in two patients were also
      noticed. This was confirmed by CT and MRI for those sites. Tc-99m HMPAO appears
      to be a useful agent for the localization of both the primary focus and
      unexpected metastatic lesion in patients with malignant melanoma.

PMID- 7648740
TI  - Thallium-201 uptake in the orbits.
AB  - Thallium-201 uptake patterns in the orbits are not widely known. Diffuse,
      bilateral orbital localization of TI-201 chloride may be an incidental finding
      because of orbital muscle or other soft tissue uptake. Differences in orbital
      blood flow and soft tissue mass may be the cause of the varying uptake
      intensities in most cases. Focal uptakes, even when bilateral, may indicate
      specific pathology and should be investigated. Sample cases are presented.

PMID- 7648741
TI  - Gated versus first-pass radioangiography in the evaluation of left-to-right
      shunts.
AB  - Excluding regurgitant ventricles and multiple shunting, left-to-right shunts of
      the central circulation can be evaluated from the difference between the right
      ventricular stroke counts (SCRV) and the left ventricular stroke counts (SCLV),
      which are obtained from gated radioangiography. The pulmonary-to-systemic flow
      ratio (QP/Qs) is equated to SCRV/SCLV in atrial shunts and to SCLV/SCRV in
      ventricular and ductal shunts. In this paper, the potentials of the stroke count
      method have been compared to the gamma fit first-pass technique, incorporating
      the recent refinements in ductal shunts and deconvolution of the pulmonary curve.
      In 17 patients with left-to-right shunt, the stroke count method and the gamma
      fit method correlated moderately with oximetry (r = .71 and .87), respectively.
      The gamma variate method appeared superior in the detection and estimation of
      small shunts, whereas when QP/Qs was two or larger, the stroke count method
      yielded closer agreement with oximetry data.

PMID- 7648742
TI  - Diffuse bilateral lung uptake of TI-201 chloride in CMV pneumonitis. Case
      presentation with histopathologic correlation.
AB  - Diffuse intense lung uptake of TI-201 chloride without abnormal Ga-67 citrate in
      a case of cytomegalovirus pneumonitis in a patient with AIDS is presented. An
      autopsy performed within 4 days of imaging revealed no pulmonary pathology other
      than diffuse cytomegalovirus infection with abundant histiocytes and inclusion
      bodies and pulmonary congestive heart failure. Among the various mechanisms of TI
      201 accumulation, active transport through Na-K ATPase appears to be predominant
      in this case, as suggested by innumerable histiocytes. It is the authors'
      experience that positive TI-201 uptake without abnormal Ga-67 accumulation is
      highly specific for pulmonary Kaposi sarcoma. The presence of such discrepancy
      between TI-201 and Ga-67 uptake in AIDS patients decreases the specificity of a
      TI-201 positive/Ga-67 negative lesion for pulmonary Kaposi sarcoma, especially
      with the rising incidence of both cytomegalovirus and Kaposi sarcoma in AIDS
      patients.

PMID- 7648743
TI  - Ga-67 scintigraphy with a dual-head camera.
AB  - High quality images are necessary for correct interpretation of Ga-67 studies in
      lymphoma. The authors were interested if there is a significant change in the
      quality of the Ga-67 images using a newly introduced dual-head camera compared
      with a conventional single-head camera. The tomographic spatial resolution, full
      width at half maximum, was found to be 9.63 mm compared with 13.7 for a single
      head camera. The volume sensitivity was 380 cps/microCi/ml per axial cm as
      compared with 333 cps/microCi/ml, and point source sensitivity was 5.6
      cps/microCi compared with 3.8. There was a significant difference (P < 0.001),
      when using the threshold technique, in the number of counts per pixel over a wide
      range of volumes and concentrations in phantoms when the two cameras were
      compared. There was also a significant difference (P < 0.001) in Ga-67 uptake in
      lymphoma lesions in patients when the same parameters were used for both cameras
      when using SPECT. The average uptake in lymphoma lesions, using a dual-head
      camera, was 529 counts/pixel with a range of 112 to 1275 counts/pixel in
      different tumors. With a single-head camera, the average for the same tumor was
      216 counts/pixel with a range of 59 to 469 counts/pixel. The high sensitivity of
      the dual-head camera enabled high-quality, whole body scintigraphy, including the
      limbs, in 20 minutes compared with the 35 minutes necessary for the single-head
      camera for images which did not include the legs. Whole body Ga-67 scintigraphy
      is shown to be important in patients with lymphoma of the upper and lower
      limbs.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7648744
TI  - Intrarenal arteriovenous fistula simulating a hypervascular renal tumor on
      radionuclide renal imaging.

PMID- 7648745
TI  - Bone scan in iliotibial band syndrome.

PMID- 7648746
TI  - Evaluation of Maffucci syndrome with Tc-99m oxidronate bone scintigraphy.

PMID- 7648747
TI  - Splenic metastasis from colon carcinoma imaged using In-111 OncoScint.

PMID- 7648748
TI  - Ipsilateral thigh hyperperfusion during acute testicular torsion. An incidental
      finding related to vascular reflex.

PMID- 7648749
TI  - Multicentric meningioma evaluation with Tc-99m MIBI SPECT, CT, and MRI.

PMID- 7648750
TI  - SPECT imaging in a patient with neuro-Behcet disease.

PMID- 7648751
TI  - The "Lizzie Borden" sign of increased intracranial pressure in infants.

PMID- 7648752
TI  - Bone seeking agent uptake in abdominal muscle after exercise.

PMID- 7648753
TI  - Diffuse lower hemiskeletal involvement of metastatic transitional cell carcinoma.

PMID- 7648754
TI  - Diffuse thallium lung uptake in pneumocystis pneumonia (PCP)

PMID- 7648755
TI  - Bladder variants noted on bone and renal imaging.

PMID- 7648756
TI  - Community-based therapeutic drug monitoring. Useful development or unnecessary
      distraction?

PMID- 7648757
TI  - Meropenem clinical pharmacokinetics.
AB  - Meropenem is a recently developed carbapenem antibiotic, similar to imipenem,
      with a wide spectrum of activity against Gram-positive and Gram-negative
      bacteria. In comparison with imipenem, meropenem is relatively stable to
      hydrolysis by the enzyme dehydropeptidase I (DHP-I), thus precluding the need for
      coadministration with an inhibitor of DHP-I, such as cilastatin. Furthermore,
      meropenem may be less nephrotoxic and neurotoxic than imipenem. Plasma meropenem
      concentrations reach a peak (Cmax) of approximately 30 mg/L after administration
      of a standard dose of 1 g intravenously. The elimination half-life (t1/2) is
      approximately 1 hour, and the area under the plasma concentration-time curve
      increases linearly in a dose-related manner. The volume of distribution is 21L,
      indicating predominantly extracellular distribution. Meropenem distributes partly
      into cerebrospinal fluid. The drug is eliminated both by metabolism and
      excretion. In normal volunteers, up to 70% is recovered in urine, and the
      remainder is accounted for by a beta-lactam ring-opened form of the compound, ICI
      213689. The t1/2 of meropenem is prolonged in patients with renal insufficiency
      and correlates well with creatinine clearance. Dosage adjustments in people with
      decreased creatinine clearance can, thus, be made on the basis of creatinine
      clearance.

PMID- 7648759
TI  - Drug interactions with thrombolytic agents. Current perspectives.
AB  - Thrombolytic agents are widely used for the treatment of acute thromboembolic
      diseases, especially acute myocardial infarction (AMI). These compounds include
      streptokinase, anistreplase, alteplase, urokinase and, although not commercially
      available yet, saruplase (prourokinase). The therapeutic window of these
      compounds is relatively small and subtherapeutic or toxic plasma concentrations
      may have serious clinical implications (insufficient thrombolysis, reocclusion
      and bleeding). Among the factors that affect the pharmacokinetics and
      pharmacodynamics of thrombolytic agents, comedication is especially relevant
      since these drug interactions are partly predictable and sometimes preventable.
      Based on knowledge of the pharmacology of thrombolytic agents and general
      mechanisms by which pharmacokinetic drug interactions occur, interactions with
      alteplase and saruplase are expected. The clearance of alteplase is dependent on
      hepatic blood flow (HBF), and scientific evidence is emerging that saruplase is
      also a high-clearance compound. Each pharmacological agent that alters HBF and is
      given concurrently with one of these agents can change the plasma concentrations
      of those thrombolytics. Although there are no published data confirming drug
      induced changes in the metabolism of alteplase or saruplase by this mechanism in
      humans, indirect supportive evidence (clinical observations and animal
      experiments) is available. An overview is presented of the anticipated effects of
      compounds that are frequently coadministered with thrombolytic agents on the
      pharmacokinetics of the thrombolytics with high-clearance properties. Since the
      clearance of these thrombolytics may be strongly affected by hypoperfusion of the
      liver as a result of cardiogenic haemodynamic failure, the role of circulatory
      changes in potential drug-drug interactions is also discussed. Pharmacodynamic
      drug interactions are highly relevant in the treatment of acute thrombotic
      lesions and are still being evaluated to further optimise treatment strategies.
      As most of these treatments exist as combinations of thrombolytic, antithrombin
      and antiplatelet compounds, beneficial effects are partly offset by bleeding
      complications. Changes in the pharmacokinetics and/or pharmacodynamics of
      thrombolytic agents may have serious consequences. It becomes imperative for the
      practising physician to be aware of benefits and risks of interactions with
      thrombolytic agents and especially of the fact that the principal way by which
      the pharmacokinetics of alteplase and, presumably, saruplase can be affected is
      by drug- and/or haemodynamic failure-induced changes of HBF.

PMID- 7648761
TI  - Clinical pharmacology and drug safety: lessons from hirudin.

PMID- 7648760
TI  - Pharmacokinetic optimisation of vancomycin therapy.
AB  - Renewed interest in vancomycin over the past decade has led to an abundance of
      data concerning the pharmacokinetics of vancomycin, and its dosage selection and
      concentration-response relationships. No definitive data exist that correlate
      vancomycin serum concentrations with clinical outcomes. However, inconsistencies
      in sampling times for peak serum concentrations and differences in infusion times
      make interpreting vancomycin serum concentrations difficult. Furthermore, the
      evidence implicating vancomycin as a cause of oto- or nephrotoxicity is
      circumstantial, and these adverse effects may occur only in high-risk
      populations. Owing to the variability in its dose-serum concentration
      relationship and multicompartmental pharmacokinetics, several methodologies have
      been developed for instituting and adjusting vancomycin dosages. Nomograms rely
      on a fixed volume of distribution and the relationship between vancomycin
      clearance and creatinine clearance. Since both of these factors may be altered in
      certain populations, dosage methodologies (both traditional and Bayesian) that
      use population- or patient-specific pharmacokinetic data perform better than
      standard nomograms for initiating vancomycin therapy. Controversy still exists as
      to whether a 1- or a 2-compartment model is more appropriate for making dosage
      adjustments; however, steady-state rather than non-steady-state vancomycin serum
      concentrations should be used for dosage adjustments. Certain pathophysiological
      states such as age, bodyweight and renal function contribute to altered
      pharmacokinetics and may alter the design of the dosage regimen. Since no
      definitive relationship exists between vancomycin serum concentrations and either
      clinical outcome or adverse effects, considerable controversy surrounds the
      utility of monitoring serum vancomycin concentrations. Therefore, routine
      vancomycin serum concentration monitoring may be warranted only in specific
      populations, such as patients receiving concurrent aminoglycoside therapy or
      those receiving higher than usual dosages of vancomycin, patients undergoing
      haemodialysis and patients with rapidly changing renal function.

PMID- 7648762
TI  - Plasma concentrations of triazolam are increased by concomitant ingestion of
      grapefruit juice.
AB  - BACKGROUND: Grapefruit juice increases the bioavailability of several drugs known
      to be metabolized by CYP3A enzymes. Ketoconazole and itraconazole can increase
      the area under the concentration-time curve [AUC(0-infinity)] of triazolam, a
      substrate of CYP3A, by more than twenty times. METHODS: In this randomized
      crossover study the effect of grapefruit juice on the pharmacokinetics and
      pharmacodynamics of triazolam was investigated. Ten healthy young subjects
      received a single 0.25 mg dose of triazolam with either 250 ml grapefruit juice
      or water. Plasma concentrations and effects of triazolam were measured up to 17
      hours. RESULTS: Grapefruit juice increased the AUC(0-infinity) of triazolam in
      each subject and the peak concentration in nine of the 10 subjects. The mean
      AUC(0-infinity) of triazolam was increased 1.5-fold (p < 0.001) and the peak
      concentration was increased 1.3-fold (p < 0.05) by grapefruit juice. Grapefruit
      juice postponed the peak time of triazolam from 1.6 hours to 2.5 hours (p <
      0.05). Grapefruit juice increased the effects of triazolam slightly; drowsiness
      was significantly (p < 0.05) enhanced. CONCLUSIONS: Grapefruit juice can increase
      the plasma concentrations and effects of oral triazolam.

PMID- 7648763
TI  - The in vitro degradation of cisatracurium, the R, cis-R'-isomer of atracurium, in
      human and rat plasma.
AB  - OBJECTIVE: To assess the mechanism and rate of in vitro degradation of
      cisatracurium in aqueous buffer and in human and rat plasma. METHODS:
      Cisatracurium was incubated in aqueous buffer at various pH values or in human
      and rat plasma maintained at pH 7.4 with HEPES buffer. Cisatracurium and the
      degradation products, laudanosine and the monoquaternary alcohol, were
      quantitated by HPLC with use of fluorescence detection. RESULTS: In Sorenson's
      phosphate buffer, cisatracurium degraded spontaneously by a chemical process
      commonly referred to as "Hofmann elimination." The rate of degradation increased
      with increasing pH. From pH 6.4 to 7.8 there was a 6.5-fold increase in the rate
      of degradation of cisatracurium and, on a molar basis, the final decomposition
      product laudanosine accounted for all of the drug. At a pH of 7.4, cisatracurium
      degraded with a half-life of about 34.1 +/- 2.1 minutes. Cisatracurium incubated
      in human plasma degraded with a mean (+/- SD) half-life of 29.2 +/- 3.8 minutes,
      which is consistent with Hofmann elimination. Besides laudanosine, and unlike
      that observed in Sorenson's phosphate buffer, significant amounts of the
      monoquaternary alcohol were formed that slowly degraded to laudanosine. The
      micromoles of laudanosine formed eventually accounted for the total amount of
      cisatracurium incubated with human plasma. The monoquaternary alcohol appears to
      be a product of ester hydrolysis of a monoquaternary acrylate formed during the
      first step in Hofmann elimination. Evidence for esterase involvement at this step
      in the degradation of cisatracurium was based on inhibition studies with O-cresyl
      benzodioxaphosphorin oxide (CBDP), a specific carboxylesterase inhibitor. The
      addition of CBDP to human plasma completely blocked the formation of
      monoquaternary alcohol and converted the degradation of cisatracurium to total
      Hofmann elimination. In rat plasma cisatracurium was hydrolyzed, with a half-life
      of only 3 1/2 minutes, by carboxylesterases. The addition of CBDP increased the
      half-life to 25 minutes, which is consistent with Hofmann elimination.
      CONCLUSION: In human plasma the rate-limiting step in the degradation of
      cisatracurium is Hofmann elimination, with the initial formation of a
      monoquaternary acrylate. The observation that the monoquaternary alcohol results
      from ester hydrolysis of the monoquaternary acrylate by plasma esterase(s)
      explains the presence of the monoquaternary alcohol metabolite in human plasma
      during clinical studies with cisatracurium. The rapid hydrolysis of cisatracurium
      by rat plasma relative to human indicates a major species difference in plasma
      esterase(s).

PMID- 7648758
TI  - Influence of endogenous and exogenous effectors on the pharmacokinetics of
      theophylline. Focus on biotransformation.
AB  - Theophylline has been widely used as a bronchodilatory drug for the treatment of
      neonatal apnoea in premature newborns and patients with obstructive airways
      disease. The development of analytical equipment and procedures to determine the
      systemic concentration of theophylline renders it possible to improve the
      effectiveness of theophylline therapy and reduce the incidence of toxic and
      adverse effects. Since the beginning of the 1970s, endogenous and exogenous
      factors (e.g. age, blood pH, concomitant diseases and drug therapy, meal
      preparation procedure, nutritional habits, pregnancy, gender, smoking and, to a
      lesser extent, biorhythms), influencing nearly all parameters of theophylline
      pharmacokinetics have been described. Drug absorption depends on galenic
      formulation, drug delivery, nutritional habits and the chemical derivatives used.
      The mean plasma protein binding rates depend on the method of plasma protein
      determination: acidic blood pH values and advanced age may result in reduced
      plasma proteins. The volume of distribution depends primarily on age; it is 2
      fold greater in newborns than in adults. Furthermore, changes in blood pH values,
      the plasma protein content and the administration of concomitant drugs may vary
      this parameter. Biotransformation is the most clinically important
      pharmacokinetic parameter. Hepatic metabolism accounts for 90% of the metabolism
      of theophylline. Essentially, 2 microsomal isoenzymes of the cytochrome P450
      system appear to be responsible for the N-methylation and 8-hydroxylation of the
      drug. Age and concomitant disease are the major endogenous effectors influencing
      biotransformation of theophylline, whereas biorhythms, gender and pregnancy are
      of lesser importance. Exogenous factors, such as concomitantly administered
      drugs, smoking and nutritional factors, affect biotransformation by inducing or
      inhibiting the metabolising enzymes. Because of intra- and interindividual
      variability in the pharmacokinetics of theophylline, which may be increased by
      the presence of endogenous and/or exogenous effectors, it is necessary to
      supervise theophylline therapy by therapeutic drug monitoring if target
      concentrations are to be achieved.

PMID- 7648764
TI  - Comparison of the kinetic disposition and metabolism of E3810, a new proton pump
      inhibitor, and omeprazole in relation to S-mephenytoin 4'-hydroxylation status.
AB  - We studied the kinetic disposition and metabolism of E3810 [(+/-)-sodium 2-[[4-(3
      methoxypropoxy)-3-methylpyridin-2-yl]methylsulfinyl ]-1H- benzimidazole], a new
      proton pump inhibitor, and omeprazole in 15 Japanese male volunteers, six of whom
      were poor metabolizers and nine of whom were extensive metabolizers of S
      mephenytoin. All received once-daily 20 mg doses of E3810 or omeprazole for 7
      days in a randomized crossover manner, with a 3-week washout period between the
      two trial phases. The parent drugs and their principal metabolites in plasma and
      urine were measured on days 1 and 7 after drug administration. The mean values
      for area under the plasma concentration-time curve (AUC) of omeprazole were 6.3-
      and 4.4-fold greater, whereas those of E3810 were 1.8- and 1.9-fold greater in
      poor metabolizers than in extensive metabolizers after the first and final doses,
      respectively. Although the mean AUC values for both drugs were significantly (p <
      0.01 or p < 0.05) greater in poor metabolizers than in extensive metabolizers,
      the difference in the AUC between the two groups was smaller after E3810 than
      after omeprazole administration. The AUC of omeprazole tended to increase with
      the repeated doses in extensive metabolizers, whereas no such change was observed
      for E3810. The urinary excretions of the principal metabolite(s) of two proton
      pump inhibitors also reflected the data derived from plasma samples in relation
      to S-mephenytoin 4'-hydroxylation status. We conclude that the metabolism of two
      proton pump inhibitors is under coregulatory control of S-mephenytoin 4'
      hydroxylase (CYP2C19), but that the magnitude of CYP2C19-mediated metabolism
      appears to differ between the two drugs. In contrast to omeprazole, the
      metabolism of E3810 is less saturable in extensive metabolizers during the
      repetitive dosings.

PMID- 7648765
TI  - Comparison of the interaction potential of a new proton pump inhibitor, E3810,
      versus omeprazole with diazepam in extensive and poor metabolizers of S
      mephenytoin 4'-hydroxylation.
AB  - OBJECTIVE: To compare the interaction potential of E3810, [(+/-)-sodium 2-[[4-(3
      methoxpropoxy)-3-methylpyridin-2-yl]methylsulfinyl] -1H-benzimidazole] a new
      proton pump inhibitor, and omeprazole with diazepam in relation to S-mephenytoin
      4'-hydroxylation status. STUDY DESIGN: Fifteen healthy male volunteers consisting
      of six poor metabolizers and nine extensive metabolizers of S-mephenytoin 4'
      hydroxylation participated in the study, where two poor and three extensive
      metabolizers each as a group were randomly allocated to one of the three
      different treatment sequences with a 3-week washout period among the three trial
      phases. Each volunteer received an oral once-daily dose of E3810 (20 mg),
      omeprazole (20 mg), or placebo for 23 days and an intravenous dose (0.1 mg/kg) of
      diazepam on posttreatment day 8. Plasma concentrations of diazepam and
      demethyldiazepam were measured up to 16 days after the administration of
      diazepam. RESULTS: Diazepam was more slowly metabolized in the poor metabolizers
      than in the extensive metabolizers. No significant effects of E3810 and
      omeprazole on any kinetic parameters of diazepam were observed in the poor
      metabolizers. In the extensive metabolizers, omeprazole significantly decreased
      the mean clearance of diazepam and increased its half-life, area under the plasma
      concentration-time curve, and mean residence time compared with E3810 and placebo
      (p < 0.05 or 0.01), whereas no changes in these kinetic parameters were observed
      during the treatment with E3810. Omeprazole significantly increased the mean area
      under the plasma concentration-time curve (0-16 days) of demethyldiazepam in the
      extensive metabolizers compared with placebo (p < 0.01), whereas E3810
      significantly increased it in the poor metabolizers compared with omeprazole or
      placebo (p < 0.05). CONCLUSION: The results indicate that E3810 as a substrate
      goes less toward S-mephenytoin 4'-hydroxylase (CYP2C19) and has a much weaker, if
      any, potential to interact with diazepam compared with omeprazole.

PMID- 7648767
TI  - Verapamil stereoisomerism: enantiomeric ratios in plasma dependent on peak
      concentrations, oral input rate, or both.
AB  - OBJECTIVE: To determine if R/S enantiomeric ratios of verapamil in plasma are
      affected by the changes in plasma concentration-time profiles of total verapamil,
      which result from administration of oral formulations with different input rates.
      METHODS: Twelve young (19 to 37 years old) healthy men received 240 mg single
      oral doses of racemic verapamil as immediate-release (fasting) and sustained
      release (fed) formulations in a randomized, crossover (7-day washout) study.
      Serial blood samples were taken over a 48-hour period, and PR intervals were
      measured at times close to blood drawings for the first 16 hours. RESULTS: Marked
      enantiospecific disposition of verapamil occurred, with oral clearance values of
      40.8, 25.3, and 121 ml/min/kg for the total verapamil, R-verapamil, and S
      verapamil, respectively. Wide input-rate differences also occurred between the
      immediate- and sustained-release formulations (mean [% coefficient of variation];
      peak concentration [Cmax] [total], 327 [44%] versus 73 [58%] ng/ml; time to reach
      Cmax [total], 1.71 [36%] versus 10.8 [62%] hours). The mean extent of total
      verapamil bioavailability from the sustained-release formulation was 73.3% of the
      immediate-release formulation. The R/S ratios at Cmax (total) and at several
      other time periods were lower, with the immediate-release formulation for both
      verapamil (R/S = 4.52 [13%] versus 5.83 [18%]; p < 0.01) and norverapamil (R/S =
      2.48 [16%] versus 3.04 [19%]; p < 0.01). CONCLUSIONS: Significantly different R/S
      ratios of verapamil occurred in the plasma with oral formulations that had
      substantially different rates of input. With the immediate-release formulation
      the total verapamil Cmax was higher than that observed with the sustained-release
      formulation, and the percentage of the pharmacologically more active S-verapamil
      in the total was also higher (lower R/S ratio). These findings were attributed to
      the concentration- and/or input-rate-related saturable hepatic first-pass
      metabolism of the S-verapamil.

PMID- 7648766
TI  - Central nervous system effects of subdissociative doses of (S)-ketamine are
      related to plasma and brain concentrations measured with positron emission
      tomography in healthy volunteers.
AB  - Plasma concentrations, maximum regional brain concentrations, and specific
      regional binding in the brain after administration of 0, 0.1, and 0.2 mg/kg doses
      of (S)-ketamine were measured in a randomized, double-blind, crossover study in
      five volunteers and were related to induced effects such as analgesia, amnesia,
      and mood changes. Specific binding in the brain was assessed by simultaneous
      administration of (S)-[N-methyl-11C]ketamine quantified by positron emission
      tomography. High radioactivities in the brain corresponded to regional
      distribution of N-methyl-D-aspartate receptor complexes. A significant and dose
      dependent reduction of binding was measured as a result of displacement of (S)-[N
      methyl-11C]ketamine. Memory impairment and psychotomimetic effects were related
      to dose, plasma concentration 4 minutes after administration, and decreased
      regional binding of (S)-ketamine in the brain and were consistently seen at
      plasma and maximum regional brain (S)-ketamine concentrations higher than 70 and
      500 ng/ml, respectively. The magnitude of specific binding of (S)-ketamine,
      measured with positron emission tomography, can be related directly to drug
      effects.

PMID- 7648768
TI  - Pharmacokinetics and pharmacodynamics of rocuronium at the vocal cords and the
      adductor pollicis in humans.
AB  - The pharmacokinetic-pharmacodynamic relationship of rocuronium at the laryngeal
      adductor muscles and the adductor pollicis was determined in eight patients
      during general anesthesia. Rocuronium was administered as an infusion at a rate
      of 100 micrograms.kg-1.min-1 over 5 minutes. The half-life of transport between
      plasma and biophase (effect compartment) was significantly shorter at the
      adductor laryngeal muscles (2.7 +/- 0.6 minutes, mean +/- SD) than at the
      adductor pollicis (4.4 +/- 1.5 minutes, p = 0.003). The concentration in the
      effect compartment producing 50% of the maximum effect was significantly greater
      at the adductor laryngeal muscles (1424 +/- 148 micrograms.L-1) than at the
      adductor pollicis (823 +/- 157 micrograms.L-1, p = 0.0001). The shorter onset of
      neuromuscular blockade at the laryngeal muscles than at the adductor pollicis may
      be explained by a faster transfer rate at the laryngeal adductor muscles
      neuromuscular junction than at the adductor pollicis neuromuscular junction.

PMID- 7648769
TI  - Length/serum creatinine ratio does not predict measured creatinine clearance in
      critically ill children.
AB  - OBJECTIVE: Information regarding renal function is important in critically ill
      children to adjust the dosage of drugs that are eliminated by the kidneys.
      Methods for estimating glomerular filtration rate (GFR) based on age and serum
      creatinine level have shown good agreement with measured creatinine clearance
      (CLCR) in children without critical illness but have not been examined in
      critically ill children. METHODS: CLCR (24 hours) was measured (CLCR-measured) in
      100 individuals (aged 5.6 years [range, 0.1 to 20.8 years]) admitted to a
      pediatric intensive care unit. Urine was collected by indwelling bladder
      catheters. Serum levels were determined. CLCR was calculated (CLCR-measured)
      according to the standard formula. GFR was estimated (CL-estimated) according to
      a published method, in which GFR is based on serum creatinine levels, patient
      length, and a constant that varies with the age and sex of the child. For each
      patient, the percentage difference between methods was calculated as the
      difference between the methods divided by the average obtained by the two methods
      and expressed as a percentage. Bias was calculated as the absolute value of the
      percentage difference. RESULTS: CLCR-measured and CL-estimated were significantly
      correlated (CLCR-measured = 0.57 CL-estimated + 16.8; r = 0.68; p < 0.001).
      However, CL-estimated was greater than CLCR-measured in 84 patients. The
      difference ranged from -230 to +123 ml/min/1.73 m2 (mean -25.9 ml/min/1.73 m2
      [95% confidence interval, -18.1 to 33.7 ml/min/1.73 m2]). The mean percentage
      difference between the methods was also large (-38.1% [95% confidence interval, 
      47.1% to 29.2%]) and ranged from -153.2% to 102.1%. The mean bias was 45.2% (95%
      confidence interval, 37.7% to 52.8%). In 36 of 100 patients the discrepancy
      between the two methods was greater than 50%. Adjusting for weight percentile, as
      a proxy for abnormal muscle mass, did not improve the model. CONCLUSION: A method
      to estimate GFR in children that is based on age and sex, but not critical
      illness, does not correspond with measured 24-hour CLCR. Use of this method to
      adjust dosage of drugs eliminated by the kidney might result in significant
      overdosage in most critically ill children.

PMID- 7648770
TI  - Dipyrone metabolism in liver disease.
AB  - BACKGROUND AND OBJECTIVES: Dipyrone is an analgesic, antipyretic, and anti
      inflammatory drug. After oral administration it is hydrolyzed to 4
      methylaminoantipyrine and further metabolized to 4-aminoantipyrine, 4
      formylaminoantipyrine, and 4-acetylaminoantipyrine. This study investigated the
      disposition of dipyrone metabolites in 12 hospitalized patients with cirrhosis
      (age, 25 to 65 years) and 27 healthy subjects of two age groups (young, 21 to 40
      years; elderly, 73 to 90 years). METHODS: Subjects received 1 gm dipyrone orally,
      and blood samples were drawn and urine collected over 72 hours. Plasma and urine
      concentrations of the four metabolites were determined by HPLC. RESULTS: 4
      Methylaminoantipyrine terminal elimination half-life (t1/2 beta) in patients with
      cirrhosis was prolonged compared with young and elderly subjects (mean +/- SEM,
      10.6 +/- 0.6 versus 3.1 +/- 0.2 and 4.9 +/- 0.6 hours, p < 0.001), and the
      nonrenal clearance was reduced compared with the young subjects (1.069 +/- 0.243
      versus 2.165 +/- 0.154 ml/min/kg, p < 0.005). 4-Formylaminoantipyrine was
      undetectable in two patients and in the remaining 10 patients, t1/2 was longer
      than in the young subjects (26.4 +/- 4.3 versus 10.8 +/- 0.7 hour, p < 0.01),
      whereas the elderly had intermediate values (18.1 +/- 2.8 hours). Clearance for
      production of 4-formylaminoantipyrine was reduced in the patients with cirrhosis
      than in the young and elderly subjects (0.109 +/- 0.024 versus 0.363 +/- 0.031
      and 0.340 +/- 0.053 ml/min/kg, p < 0.001). The acetylation phenotype was
      determined to evaluate the pharmacokinetic parameters of 4-aminoantipyrine and 4
      acetylaminoantipyrine. Prolongation of the 4-aminoantipyrine t1/2 and decrease in
      its clearance for production was found for the patients with cirrhosis, both slow
      and rapid acetylators, compared with the young and elderly subjects (p < 0.01). 4
      Acetylaminoantipyrine t1/2 was also prolonged for patients with cirrhosis, slow
      and rapid acetylators, compared with the young subjects (p < 0.005). In the slow
      acetylators, clearance for production of 4-acetylaminoantipyrine did not differ
      between the patients with cirrhosis and the young subjects (p < 0.5); however, a
      difference was found for the rapid acetylators (p < 0.001). CONCLUSION: Our
      results show that the disposition of 4-methylaminoantipyrine, 4-aminoantipyrine,
      4-formylaminoantipyrine, and 4-acetylaminoantipyrine is reduced by chronic liver
      disease after a single oral dose of dipyrone.

PMID- 7648771
TI  - Chlorpheniramine plasma concentration and histamine H1-receptor occupancy.
AB  - The plasma concentration-response relationship of the antihistamine
      chlorpheniramine is poorly characterized. This study examined concurrently the
      concentrations of chlorpheniramine and presence of H1-receptor antagonist in
      plasma after administration of 8 mg chlorpheniramine in normal volunteers. Six
      extensive metabolizers and five poor metabolizers, as judged by CYP2D6 phenotype
      (dextromethorphan metabolic ratio), were enrolled in the study. More than 80%
      occupancy of H1-receptors by antagonist in plasma was observed for 12 hours after
      the dose in extensive metabolizers and greater than 60% from 12 to 30 hours in
      poor metabolizers, when plasma concentrations had fallen below those that should
      result in 50% occupancy of receptors. The results suggest that (+/-)
      chlorpheniramine plasma concentrations do not predict H1-receptor antagonist in
      plasma. In addition, a role is suggested for CYP2D6 in formation of a potent
      active metabolite of chlorpheniramine.

PMID- 7648772
TI  - The effect of entacapone on the disposition and hemodynamic effects of
      intravenous isoproterenol and epinephrine.
AB  - BACKGROUND: Entacapone is a potent, selective catechol-O-methyltransferase (COMT)
      inhibitor. Entacapone could potentiate the hemodynamic effects of exogenously
      administered catecholamines, which are substrates of the COMT enzyme. DESIGN AND
      METHODS: Originally, the study was to follow a placebo-controlled, randomized
      crossover design. Because of two cases of ventricular arrhythmia, a decision was
      made to terminate the study before its completion. Six subjects went through the
      isoproterenol and epinephrine infusions while taking placebo and five other
      subjects while taking entacapone. The actual design was thus one with two
      parallel groups with random allocation and double-blind drug administration. The
      subjects were given either a single dose of 400 mg entacapone or placebo 30
      minutes before the start of isoproterenol or epinephrine infusions. Four dosages
      of epinephrine (1.5, 3, 6, or 12 micrograms/min) and isoproterenol (0.5, 1, 1.5,
      or 2 micrograms/min) were infused (5 minutes for each level). Heart rate and
      blood pressure were measured and ECG was monitored. The concentrations of
      isoproterenol and epinephrine in plasma were determined by HPLC. RESULTS: The
      maximal increase in heart rate during isoproterenol infusion after entacapone
      administration (40 +/- 11 beats/min, mean +/- SD) was statistically greater (p =
      0.0496) than after placebo administration (27 +/- 7 beats/min). The increase in
      heart rate during epinephrine infusion was 25 +/- 13 beats/min after entacapone
      administration and 14 +/- 9 beats/min after placebo administration (p = 0.127).
      There were no statistically significant differences between entacapone and
      placebo in blood pressure or in plasma concentrations of isoproterenol and
      epinephrine. CONCLUSION: We conclude that entacapone may potentiate the
      chronotropic and arrhythmogenic effects of exogenously administered isoproterenol
      and epinephrine.

PMID- 7648773
TI  - Caregiver time use: an outcome measure in clinical trial research on Alzheimer's
      disease.
AB  - OBJECTIVE: To assess whether unpaid caregiver time and paid professional time
      increase as cognitive impairment associated with Alzheimer's disease increases
      and to evaluate the utility of caregiver time as an additional outcome measure in
      clinical trial research of Alzheimer's disease. METHODS: This was a 24-week,
      double-blind, multicenter, parallel-group, placebo-controlled study conducted at
      17 clinical outpatient sites by Hoechst-Roussel Pharmaceuticals Inc. A total of
      449 patients older than 40 years with probable Alzheimer's disease of mild to
      moderate severity (criteria of the National Institute for Neurological and
      Communicative Disorders and Stroke--Alzheimer's Disease and Related Disorders
      Association) entered the study, and 284 completed both baseline and week 24 data
      collection. A total of 160 caregivers completed time allocation surveys at
      baseline and at 24 weeks. Patients with Alzheimer's disease received 150 mg/day
      and 225 mg/day Velnacrine maleate (parallel-group treatment) and placebo.
      Cognitive function was measured with use of cognitive and noncognitive subscales
      of the Alzheimer's Disease Assessment Scale (ADAS). Unpaid caregiver and paid
      professional time use were measured with use of the Caregiver Activities Time
      Survey (CATS). RESULTS: Unpaid caregiver time per day increased significantly
      with cognitive impairment at baseline as measured by the ADAS cognitive and
      noncognitive components. Velnacrine therapy significantly improved cognitive
      function relative to placebo, and this was associated with decreased unpaid
      caregiving time at trend levels. Specifically, caregivers of patients in the high
      dose velnacrine group (225 mg/day) experienced a partial release from their time
      involvements, especially in the area of patient supervision, by an average of 3.3
      hours per day. CONCLUSIONS: To our knowledge, this study represents the first
      time that the ADAS has been linked to a caregiver outcome. Results suggest that
      unpaid caregiver time allocation is sensitive to changes in cognitive function
      and therefore may be useful as an additional outcome measure in clinical trials
      of pharmaceutical interventions for Alzheimer's disease.

PMID- 7648774
TI  - The role of oral dihydroergotamine in the management of vascular disorders.

PMID- 7648775
TI  - Further notes on physiologic indirect response models.

PMID- 7648776
TI  - USAN Council. List No. 374. New names. Bivalirudin. Desirudin.

PMID- 7648777
TI  - The detection of autoantibodies to pancreatic islet cells by immunoenzyme
      histochemistry.
AB  - Using horseradish peroxidase- or alkaline phosphatase-conjugated secondary
      antibodies, an immunohistochemical assay was established for the detection of
      islet cell cytoplasmic antibodies (ICA). Determination of end-point titers showed
      a significant correlation between the conventional immunofluorescence and either
      immunocytochemistry assay. The assays with the enzyme-conjugated antibodies were
      more sensitive than the indirect immunofluorescence assay. Because of its
      simplicity, specificity, and easy microscopic evaluation of the chromogenic
      reaction product at the site of ICA binding, the indirect immunoperoxidase
      technique proved to be most suitable. This technique detected frequencies of ICA
      positives among newly diagnosed insulin-dependent (IDDM), noninsulin-dependent,
      and at-risk subjects that were comparable with previous studies. Preabsorption of
      ICA-positive sera with either rat or porcine brain extracts, containing the
      glutamate decarboxylase antigen, differently blocked, reduced or did not affect
      ICA reactivity with human or porcine pancreas sections. Testing of sera on human,
      bovine, and porcine pancreas sections demonstrated heterogeneity in ICA-binding
      with a high proportion of ICA false-positives on bovine pancreas. The results
      demonstrated that immunohistochemical techniques for detecting ICA are, in
      several aspects, preferable to indirect immunofluorescence and that individual
      serum ICA identify various antigens on pancreas from different species. However,
      bovine or porcine pancreas could not substitute for human pancreas in the ICA
      assay.

PMID- 7648778
TI  - Insulinotropic action of AICA riboside. I. Insulin release by isolated islets and
      the perfused pancreas.
AB  - AICA riboside (0.1 to 1.0mM) caused a concentration-related increase of insulin
      output caused by D-glucose (5.6 to 20.0mM) in either rat isolated pancreatic
      islets or perfused pancreases. In the latter model, the rate of insulin release
      was further enhanced upon removal of AICA riboside from the perfusate. No
      insulinotropic action of AICA riboside was observed in the absence of D-glucose
      or at a low concentration (2.8mM) of the hexose. Preincubation of isolated islets
      for 30 min in the presence of AICA riboside (0.5 to 1.0mM) also enhanced insulin
      release recorded over 60 min incubation, in the absence of AICA riboside, but
      presence of either D-glucose (8.3mM), 2-ketoisocaproate (10.0mM), or the
      association of D-glucose (5.6 mM) and 2-ketoisocaproate (5.0 mM). The
      preincubation of the islets with AICA riboside failed, however, to augment the
      later secretory response to the association of L-leucine (10 mM) and either L
      glutamine (10 mM) or L-asparagine (10 mM). In perfused pancreases exposed to 6 mM
      D-glucose, the presence of L-asparagine (10 mM) did not augment the
      insulinotropic action of AICA riboside. It is concluded that AICA riboside
      displays positive insulinotropic potential. However, the determinants of such an
      insulinotropic action remain to be elucidated.

PMID- 7648779
TI  - Insulinotropic action of AICA riboside. II. Secretory, metabolic and cationic
      aspects.
AB  - Preincubation of rat pancreatic islets with AICA riboside (0.1 to 1.0mM) caused a
      concentration-related stimulation of both 45Ca net uptake and insulin release
      evoked by 8.3 mM D-glucose, but failed to affect the conversion of D-[5
      3H]glucose to 3HOH, the generation of 14CO2 and 14C-labelled amino acids or
      acidic metabolites from D-[U-14C]glucose, and the islet content in ATP, ADP or
      AMP. The secretory response to AICA riboside was not suppressed in islets
      preincubated with methotrexate. AICA riboside caused a progressive decrease in
      86Rb outflow from prelabelled islets perifused at 2.8 or 6.0mM D-glucose. This
      effect faded out at a higher concentration of D-glucose (16.7 mM), in which case
      AICA riboside nevertheless provoked a delayed, progressive and not rapidly
      reversible enhancement of insulin output. At concentrations up to 0.4 mM, ZTP
      only exerted a modest effect on the activity of KATP-channels in inside-out
      patches of dispersed mouse islet cells. These findings raise the question whether
      the insulinotropic action of AICA riboside may be attributable to the sequential
      generation of ZMP, ZDP and ZTP from the nucleoside.

PMID- 7648780
TI  - Influence of metabolic control on the ventilatory threshold in adults with non
      insulin-dependent diabetes mellitus.
AB  - Metabolic control, as assessed by glycosylated hemoglobin (HbA1c), has been
      reported to have a relationship to various submaximal exercise responses.
      However, due to the narrow range of HbA1c and the limited exercise data from
      previous studies on individuals with diabetes, little support for the above
      statement exists in the literature. The current study assessed the relationship
      between HbA1c and submaximal, or ventilatory threshold (VT), and maximal exercise
      (VO2 peak) responses in subjects with non-insulin-dependent diabetes mellitus
      (NIDDM). Sixteen subjects (age = 56.5 +/- 14.4 yrs; Wt = 82.6 +/- 17.2 kg; B.M.I.
      = 29.5 +/- 2.7 kg.m-2) performed a ramp (20 watts.min-1) leg cycle ergometer test
      (GXT). Their HbA1c was 11.8 +/- 2.8% (range 6.5 to 16.6%). Breath by breath
      respiratory analysis was performed using a Med Graphics 2001 cart. Ventilatory
      threshold (VT) was determined using the V-slope method. The VT was 1,151 +/- 487
      ml.min-1 or 70.2 +/- 10% VO2peak; VO2peak was 1,645 +/- 740 ml.min-1. There were
      no significant relationships found between HbA1c and the VO2 at the VT (r =
      0.04), the % of VO2peak at the VT (r = 0.23), and the VO2peak (r = 0.17). In
      conclusion, metabolic control, as assessed by HbA1c, did not influence selected
      submaximal and maximal exercise responses in NIDDM. Therefore, exercise
      prescription for individuals with NIDDM may not need to consider the individual's
      HbA1c concentration as a modifier of their exercise response.

PMID- 7648781
TI  - Feeding an isocaloric omega-3 fatty acid diet reduces the brush border membrane
      vesicle uptake of glucose in streptozotocin-diabetic rats.
AB  - Glucose uptake is increased into the intestine of diabetic rats, and this
      adaptation can be modified further by manipulation of the type of fatty acids in
      the triglycerides in the diet. Jejunal brush border membrane vesicles were used
      to examine the uptake of D-glucose into the jejunum of non-diabetic control and
      streptozotocin-diabetic rats fed for two weeks in isocaloric semisynthetic diet
      enriched with saturated fat (beef tallow) or polyunsaturated omega-3 fatty acids
      (fish oil). The time-course of uptake of 100 microM glucose demonstrated an
      overshoot which peaked at approximately 30 seconds and declined thereafter to an
      equilibrium plateau. In concentration studies, glucose uptake was greater into
      brush border membrane vesicles of diabetic as compared with control rats. The
      maximal transport rate (Vmax) was increased approximately 9-fold in diabetics as
      compared with control rats fed beef tallow (p < 0.05), and was increased
      approximately 6-fold in diabetic rats fed fish oil. In diabetic rats, feeding
      fish oil reduced the value of the Vmax by approximately 50% as compared with
      diabetic rats fed beef tallow. Thus, the enhanced glucose uptake into BBM
      vesicles of streptozotocin-diabetic rats can be partially corrected by feeding an
      isocaloric semisynthetic diet enriched with polyunsaturated omega-3 fish oils.

PMID- 7648782
TI  - Long-term metabolic control and retinopathy in type I diabetes: ten-year follow
      up.
AB  - The causative relationship between metabolic control and long-term complications
      of diabetes is still under debate. Recent studies suggest that a strict glycemic
      control can often prevent the development of microcirculatory impairment but the
      role played by chronic hyperglycemia in the pathogenesis of retinopathy remains
      controversial. We report the results of a retrospective study of data collected
      on a ten-year period and concerning the relationship between glycemic control and
      retinopathy. A group of 46 Type I diabetic people was studied. Results indicate
      that the probability of developing retinopathy or of worsening the degree of a
      pre-existing retinopathy is higher in patients with poor metabolic control.
      Deterioration of metabolic control (increase of HbAlc% levels) appears to be
      related to a progression of retinal lesions. On the contrary, retinopathy is not
      influenced by aging and duration of diabetes mellitus.

PMID- 7648784
TI  - Direct comparison of standard and insulin modified protocols for minimal model
      estimation of insulin sensitivity in normal subjects.
AB  - Estimates of in vivo insulin sensitivity (S1) can be derived from minimal model
      analysis of a frequently sampled intravenous glucose tolerance test (FSIVGTT).
      Modification of the FSIVGTT by administration of tolbutamide improves the
      correlation between S1 and more traditional glucose clamp measurements. Recently,
      a modified FSIVGTT using insulin infusion (instead of tolbutamide) has been
      described. This modification may be useful for studying subjects with poor
      insulin secretion. We directly compare the standard FSIVGTT with the insulin
      modified FSIVGTT in ten normal subjects (age 29 +/- 2 yr, BMI 22.5 +/- 1.2
      kg/m2). Each subject received both tests. The order of the studies was randomized
      and the interval between paired studies was approximately one week. After an
      overnight fast, glucose (0.3 g/kg) was infused from time 0 to 2 min. For the
      modified FSIVGTT, insulin (4 mUkg-1.min-1) was infused from time 20 to 25 min.
      None of the subjects became hypoglycaemic after insulin infusion. Paired t-test
      analysis did not reveal significant differences between the two protocols for any
      of the minimal model parameters. The standard FSIVGTT gave estimates for S1 of
      5.63 +/- 1.32 x 10(-4) min-1 per microU/ml while the insulin modified FSIVGTT
      gave estimates for S1 of 5.11 +/- 0.83 x 10(-4) min-1 per microU/ml. However, the
      fractional standard deviation for S1 was significantly smaller with the insulin
      modified protocol (3.6 +/- 1.0 vs. 22.2 +/- 9.0, p < 0.037). Thus, under our
      experimental conditions, insulin infusion during FSIVGTT appears to improve the
      precision of minimal model estimation of S1 in normal subjects.

PMID- 7648783
TI  - Blood coagulation and fibrinolysis in obese NIDDM patients.
AB  - Four group of age- and sex-matched patients were studied: 1. nondiabetic subjects
      (n = 20) with a body mass index (BMI) < 25 Kg/m2 (lean control subjects); 2.
      obese non diabetic subjects (n = 22) with a BMI > 30 Kg/m2 (obese control
      subjects); 3. lean NIDDM subjects (n = 22); and 4. obese NIDDM subjects (n = 24).
      We determined: total cholesterol, triglycerides, HDL-cholesterol, blood glucose,
      Apolipoproteins A1 and B, insulin, Lp(a), Factor VII, fibrinogen, plasminogen, t
      PA(Ag) pre and post venous occlusion (VO) and PAI activity pre and post VO. In
      addition to metabolic abnormalities obese non diabetic subjects and lean and
      obese NIDDM patients displayed significantly higher levels of fibrinogen, Factor
      VII, plasminogen, PAI pre and post VO and tPA(Ag) pre VO and significantly lower
      levels of t-PA(Ag) post VO. Our findings demonstrate an impairment of the
      haemostatic and fibrinolytic mechanisms which may be a key role in the
      pathogenesis of atherosclerotic vascular complications in obesity and in NIDDM.

PMID- 7648786
TI  - Plasma endothelin levels in NIDDM patients with macroangiopathy.
AB  - To determine whether plasma endothelin, a potent vasoconstrictive peptide, is
      elevated in NIDDM patients, we compared a group of 15 NIDDM patients with
      macroangiopathy of mean age 60.60 +/- 2.33 years with 15 NIDDM randomly selected
      matched patients without macroangiopathy. Plasma endothelin levels were
      significantly increased in NIDDM patients with macroangiopathy (4.22 +/- 0.57
      pmol/L) and in NIDDM patients without macroangiopathy (3.81 +/- 0.51 pmol/L).
      Although endothelin values did not differ between NIDDM groups, both represented
      significant difference from control values (2.46 +/- 0.24 pmol/L). No significant
      correlations were found between plasma endothelin and age (rs = 0.11), duration
      of diabetes mellitus (rs = 0.06), BMI (rs = 0.19), plasma glucose (rs = 0.15),
      plasma fructosamine (rs = 0.02). These findings confirm that in diabetes mellitus
      a primary disturbance in endothelin production from vascular endothelium exists
      as an early phenomenon rather than a result of advanced stage of the disease.

PMID- 7648785
TI  - Intestinal absorption of vitamin A in streptozotocin-induced diabetic rats.
AB  - Diabetes mellitus is known to be associated with enhanced intestinal absorption
      of lipids. A validated in vitro technique was used to examine the uptake of (3H)
      retinol (a lipid soluble vitamin) into the jejunum and ileum of streptozotocin
      (STZ)-induced diabetic rats. In addition, availability of vitamin A in the plasma
      and liver of diabetics which were pair-fed to non-diabetic control rats was
      investigated. The relationship between the duration of incubation and retinol
      uptake was curvilinear in both the jejunum and the ileum, but no difference in
      intestinal uptake was observed between the two groups of animals. A linear
      relationship was noted between the concentration of retinol and uptake into both
      the jejunum and ileum. There was no difference in the uptake of retinol between
      the diabetic and control animals. The hepatic concentration of vitamin A also
      remained unaffected by diabetes as indicated by similar values found between pair
      fed diabetic and non-diabetic control rats. Unlike the liver, plasma retinol
      level was decreased in the diabetic animals; this effect does not appear to be
      caused by any change in the intestinal absorption of the vitamin.

PMID- 7648787
TI  - A novel effect of selenium on streptozotocin-induced diabetic mice.
AB  - The effect of oral administration of sodium selenite on glucose homoeostasis was
      studied in male Swiss albino mice 6 weeks after they were made diabetic with
      streptozotocin. Diabetes caused hyperglycaemia (2.5-fold), a marked decrease (4.5
      fold) in liver glycogen, a 4-fold increase in the glucose-6-phosphatase activity
      and significant decrease in plasma insulin levels and protein kinase activity.
      Although selenium administration in control animals showed no significant effect
      on various parameters measured, selenite treatment of diabetic mice restored
      these parameters to near control values. Thus the results show insulin-like in
      vivo action of selenium in diabetic mice.

PMID- 7648788
TI  - The role of plasma, erythrocyte and platelet myo-inositol levels in the
      development of diabetic microangiopathy.
AB  - In this study the plasma, erythrocyte, and platelet myo-inositol levels in 24
      type I, 24 type II diabetics, and in 15 healthy controls were determined. The
      diabetics were devided into two groups with microangiopathy (n = 26) and without
      microangiopathy (n = 22). The plasma, erythrocyte, and platelet myo-inositol
      levels in the whole diabetic group and control subjects were as follows. Diabetic
      group: 46.5 +/- 39.8 mumol.l-1 23.3 +/- 19.8 nmol.ml-1, 2.6 +/- 2.8 nmol.ml-1
      (10(5) cells)-1. CONTROL GROUP: 17.4 +/- 3.7 mumol.l-1, 12.2 +/- 5.2 nmol.ml-1,
      1.5 +/- 0.9 nmol.ml-1 (10(5) cells)-1. The values of the diabetic group were
      significantly higher than the values of the control group (p < 0.01). In patients
      with HbA1c levels more than 9% plasma, erythrocyte, and platelet myo-inositol
      values were significantly higher than the values of the group with HbA1C levels
      less than 9% (p < 0.05, p < 0.05 and p < 0.01). In diabetics without
      complications plasma and erythrocyte myo-inositol levels were higher than the
      values of the control group (p < 0.01), whereas there was no significant
      difference between the platelet myo-inositol values. In diabetics with
      complication all these three values were higher than those of the control group
      (p < 0.01, p < 0.01, p < 0.01). The most profound increase in the plasma,
      erythrocyte, and platelet myo-inositol levels were seen in complicated diabetics
      with a diabetes duration of 6-10 years (p < 0.01). After 10 years duration the
      values declined. In the group without complication there was no difference
      according to the duration of diabetes.

PMID- 7648789
TI  - Methodological issues in the application of the minimal model: effects of glucose
      dose, basal glucose concentration, test duration and modelling constraint.
AB  - An intravenous glucose tolerance test (IVGTT) glucose dose of 0.3 g/kg has been
      adopted for measurement of insulin sensitivity using the minimal model.
      Traditionally, however, a dose of 0.5 g/kg has been used, which might be expected
      to improve the IVGTT insulin response and hence the effectiveness of minimal
      model analysis. In a preliminary study of 5 subjects given 0.3 and 0.5 g/kg
      IVGTTs, each lasting 120 minutes, we found a 53% increase in IVGTT insulin
      response at the higher dose, but there was a marked discrepancy in the difference
      between fasting and final glucose concentrations (-0.17 mmol.l-1 at 0.3 g/kg and 
      1.01 mmol.l-1 at 0.5 g/kg). Good agreement obtained between estimates of Si
      derived from 0.3 and 0.5 g/kg IVGTTs (mean Si: 0.3 g/kg test = 6.0 min-1.microU
      1.ml, 0.5 g/kg test = 5.8 min-1.microU-1.ml: r = 0.97, p < 0.001) providing the
      final IVGTT glucose concentration rather than the fasting concentration was taken
      as the basal level for modelling analysis. These findings were confirmed and
      extended in two further studies; firstly in an analysis of the effects of choice
      of basal glucose concentration and the application of various modelling
      constraints in a cross-section of 66 subjects with a wide range of insulin
      sensitivities; then in a further study in which seven subjects were each given
      two 0.3 g/kg IVGTTs and one 0.5 g/kg IVGTT, with each test being prolonged to 300
      minutes. Agreement between estimates of Si at the two different doses was again
      only achieved by taking the final IVGTT glucose concentration as basal (mean Si:
      0.3 g/kg test = 4.7 min-1.microU-1.ml, 0.5 g/kg test = 3.8 min-1.microU-1.ml: r =
      0.75, p < 0.05), although one anomalous test required that a constraint be
      applied to the modelling process for this agreement to obtain. Closest agreement
      between the 300 minute 0.3 and 0.5 g/kg IVGTTs was found when tests were modelled
      up to 180 minutes. An IVGTT duration of 180 minutes appears to be optimum for re
      establishing the basal concentration necessary for effective modelling analysis.
      Application of constraints can markedly affect certain analyses and may introduce
      some bias; their use should be carefully monitored, although their effect on
      large datasets is likely to be small.

PMID- 7648790
TI  - Analysis of serum apolipoprotein A-I in elderly non-insulin-dependent diabetic
      patients.
AB  - Quantitative and qualitative modifications of plasma apolipoproteins could
      provide additional information in predicting coronary heart disease (CHD) in non
      insulin-dependent diabetes mellitus (NIDDM). We examined 17 men and 15 women aged
      over 65 years affected by NIDDM. Alcohol intake, smoking habits, antidiabetic
      therapy, body weight, stature, and body mass index were considered. Furthermore,
      serum lipids and apolipoprotein A-I and B levels were determined. Apo A-I was
      characterized by isoelectric focusing (IEF) and immunoblotting. The men were
      heavier and taller than the women. The women had significantly higher serum
      levels of total cholesterol, HDL-cholesterol, and apo A-I than the men. The
      levels of HDL-cholesterol, apo A-I and B were significantly influenced by an
      interaction between sex and the duration of diabetes. An invariant pattern was
      observed for apo A-I isoforms in samples from diabetic subjects of both sexes.
      The percentage distribution of serum apo A-I isoforms determined by densitometry
      is quite different from that previously reported in the literature for the
      general population. Quantitative modification in apo A-I isoforms could be due to
      the specific pathology and these variations could partly explain reduced levels
      of HDL-cholesterol in diabetic patients.

PMID- 7648791
TI  - Increased susceptibility of LDL to in vitro oxidation in patients with insulin
      dependent and non-insulin-dependent diabetes mellitus.
AB  - The susceptibility of LDL to copper-catalyzed oxidation was evaluated in 24
      patients with insulin-dependent and 16 patients with non-insulin-dependent
      diabetes mellitus, 14 abdominal and 14 gluteal-femoral obese women, 22 familial
      hypertriglyceridemic and 28 control subjects. Differences in the LDL
      susceptibilities were studied by measuring the changes of fluorescence intensity
      and expressed as lag-phase. The lag-phase was significantly shorter in patients
      with insulin-dependent, non-insulin-dependent diabetes mellitus, abdominal
      obesity and familial hypertriglyceridemic patients than in gluteal-femoral obese
      subjects and controls (p < 0.01). The shortest lag-phase was found in familial
      hypertriglyceridemic patients while intermediate values were found in insulin
      dependent, non-insulin-dependent and abdominal obese patients who had only a
      slight increase in triglyceride values. Similarly the lowest value of the LDL
      cholesterol to protein ratio, as expression of LDL particle size, was found in
      familial hypertriglyceridemic patients (p < 0.01), while the patients with
      insulin-dependent, non-insulin-dependent diabetes mellitus and abdominal obesity
      had intermediate values. The ratio was found to be directly correlated with the
      length of the lag-phase (r = 0.87, p < 0.001). In spite of similar triglyceride
      and cholesterol to protein ratio values, however, the length of the lag-phase was
      significantly shorter in patients with insulin-dependent diabetes mellitus than
      in those with abdominal obesity. So it is concluded that the different
      susceptibility to oxidation found in the different groups of patients is only
      partially explained by plasma triglyceride values.

PMID- 7648792
TI  - Prevention of diabetes in BB/Wor rats by injection of peritoneal exudate cells
      cultured in the presence of transforming growth factor beta (TGF-beta) and islet
      cells.
AB  - Studies of ocular immunity showed that incubation of peritoneal exudate cells
      with antigen in the presence of aqueous humor containing TGF-beta, conferred upon
      them the ability to systemically inhibit antigen-specific cellular immunity when
      injected into naive recipients. Since cell mediated immunity has been implicated
      in the destruction of the islets of Langerhans in diabetes, it was theorized that
      injection of naive diabetes prone BB/W or rats with peritoneal exudate cells pre
      cultured in the presence of islet antigen and TGF-beta might similarly inhibit
      their anti-islet immune reactions and prevent their development of diabetes.
      34.2% (13 of 38) of experimental recipient diabetes prone rats developed diabetes
      while 78.4% (29 of 37; p < 0.0005 compared to experimentals), 72.2% (13 of 18; p
      < 0.03 compared to experimentals), 68.8% (11 of 16; p < 0.09 compared to
      experimentals), and 77.7% (7 of 9; p < 0.08 compared to experimentals) of
      controls receiving peritoneal exudate cells pre-cultured alone, with TGF-beta,
      with TGF-beta and pheochromocytoma (PC12) cells, or with islets + TGF-beta + anti
      TGF-beta antibody, respectively, became diabetic. Experimental treatment did not
      markedly alter recipient spleen cell subsets, and spleen cells from protected
      rats did not confer disease protection when transferred into naive recipients.
      These data demonstrate that the above approach is efficacious and represents a
      unique strategy for preventing the development of autoimmune type I diabetes in
      an animal model.

PMID- 7648793
TI  - Prevalence of abnormal thyrotropin concentrations measured by a sensitive assay
      in patients with type 2 diabetes mellitus.
AB  - The utilisation of assays for TSH with improved sensitivity has revealed that
      abnormal TSH results are frequently observed in patients with nonthyroidal
      illnesses, such as trauma, renal diseases, liver diseases or sepsis. The aim of
      this study was to investigate the prevalence of abnormal TSH concentrations,
      using a sensitive immunometric assay, in patients with type 2 (non-insulin
      dependent) diabetes mellitus. The study population consisted of 290 type 2
      diabetics, 159 females and 131 males aged 40 to 93 years (mean 60.6 +/- 11.9
      years), hospitalised because of poor diabetic control or recent-onset diabetes
      (mean HbA1c value = 9.6 +/- 2.2%). All patients with TSH values outside the
      normal range (0.45 to 3.66 mlU/l) had FT4 assay and thyroid microsomal
      autoantibody assay performed on the same specimen of serum. Abnormal TSH
      concentrations were detected in 91 patients (31.4%). Subclinical hypothyroidism
      (high TSH, normal FT4) was most common (48.3%), followed by subclinical
      hyperthyroidism (low TSH, normal FT4) (24.2%) and by definite hypothyroidism
      (high TSH, low FT4) (23.1%). Definite hyperthyroidism (low TSH, raised FT4) was
      found in 4 patients (4.4%). None of the patients with low TSH values had
      increased FT3 concentrations. The prevalence of abnormal thyroid function test
      results was significantly higher in the female than in the male patients (40.9%
      vs. 19.8%, p < 0.0005) and in the insulin-treated patients than in those
      receiving oral hypoglycaemic agents (OHA) (37.3% vs. 23.1%, p < 0.02). Thirty
      patients with abnormal thyroid function test results (33.0%) had evidence of
      thyroid autoimmunity (titre of thyroid microsomal autoantibodies > 250 IU/l).
      Five thyroid microsomal antibody-negative patients had non-autoimmune thyroid
      diseases, 7 had nonthyroidal illnesses other than diabetes mellitus and 4 were
      receiving drugs known to affect the hypothalamic-pituitary-thyroid axis. Twenty
      seven thyroid microsomal auto-antibody-negative patients with abnormal TSH values
      (17 with subclinical hypothyroidism and 10 with subclinical hyperthyroidism), who
      were not receiving drugs known to affect TSH secretion and were free of diseases
      other than diabetes mellitus, were retested after two months of adequate
      treatment of diabetes with OHA or insulin. TSH concentrations decreased in all
      but one patient with initial subclinical hypothyroidism and increased in all
      patients with initial subclinical hyperthyroidism. These changes were coupled
      with a significant fall of glycated haemoglobin values. In view of the transient
      changes in TSH secretion, we suggest that the diagnosis of thyroid dysfunction in
      type 2 diabetics should be delayed until improvement of the metabolic status.

PMID- 7648794
TI  - Disparate effects of castration on renal structure and function in the
      streptozotocin diabetic rat.
AB  - Diabetic children are protected from the complications of diabetes until puberty,
      suggesting the involvement of a hormonal mechanism. In order to investigate the
      contribution of sex steroids to the development of diabetic nephropathy,
      castrated Wistar-Kyoto rats were made diabetic with streptozotocin and compared
      with intact diabetic rats. In intact rats, 32 weeks of diabetes resulted in
      hyperfiltration (p = 0.0001) and a marked increase in albuminuria (control, 1.3
      x/divided by 1.3 vs diabetes intact, 11.8 x/divided by 1.3 mg/day, p < 0.001).
      Concomitant structural changes included glomerular basement membrane thickening
      (diabetes, 199.2 +/- 7.9 vs control, 175.9 +/- 3.9 nm, p = 0.02) and increased
      mesangial volume (diabetes, 194 +/- 14 vs control, 129 +/- 20 microns 3, p =
      0.02). Although castration resulted in blood pressure lowering of 12 mmHg (p =
      0.0003), albuminuria increased to the same extent in intact and castrated
      diabetic rats (castrated diabetic 10.5 x/divided by 1.3 mg/day). Glomerular
      filtration rate was lower in castrated rats than in intact rats prior to
      induction of diabetes, but increased similarly with induction of diabetes.
      Castrated diabetic rats had increased mesangial volume (castrated diabetic, 213
      +/- 20 microns 3), but glomerular basement membrane thickness was lower than in
      intact diabetic rats (castrated diabetic, 179.5 +/- 4.5 nm). Thus, there is a
      dissociation between basement membrane thickening and albuminuria in this model
      of diabetic kidney disease. The mechanism of action of castration on glomerular
      function and structure remains to be elucidated but may relate to indirect
      effects such as reduction of blood pressure or renal polyol accumulation or a
      direct effect of sex steroids.

PMID- 7648796
TI  - Cochrane Collaborative Review Group: diabetes.

PMID- 7648795
TI  - The effects of in vitro and in vivo exposure to insulin upon prostaglandin E1
      stimulation of platelet adenylate cyclase activity in healthy subjects.
AB  - Insulin treatment of platelets is associated with increased prostaglandin E1
      stimulated adenylyl cyclase activity and decreased platelet aggregation. Because
      non-insulin dependent (Type II) diabetes mellitus is associated with
      hyperinsulinemia, we sought to determine the effect of insulin treatment in vivo
      and in vitro upon stimulation of platelet adenylyl cyclase by prostaglandin E1.
      Incubation of platelet-rich plasma obtained from normal subjects with 2 microM
      prostaglandin E1 resulted in a 16-fold increase in cAMP accumulation. Pre
      incubation of platelet-rich plasma with 0.7 nM insulin resulted in a 62% increase
      in prostaglandin E1 (2 microM)-stimulated cAMP accumulation (p < 0.005).
      Pretreatment of platelets with cholera toxin prior to incubation with insulin had
      no effect on subsequent prostaglandin E1-stimulated cAMP accumulation. By
      contrast, pretreatment of platelets with pertussis toxin prior to incubation with
      insulin resulted in a nearly 2-fold increase in prostaglandin E1-stimulated cAMP
      accumulation (p < 0.005). To determine whether platelets exposed in vivo to
      elevated concentrations of insulin would show similar responses, we isolated
      platelet-rich plasma from subjects before and after a 120 minute euglycemic clamp
      study in which insulin was infused (40 mU m-2min-1) intravenously. Patients who
      underwent the euglycemic clamp study achieved steady state serum levels on
      insulin of 0.70 +/- 0.19 pmol/ml. Platelets obtained after insulin infusion had a
      65% increase in prostaglandin E1-stimulated cAMP. Our results indicate that serum
      levels of insulin that are common in patients with type II diabetes mellitus can
      increase the sensitivity of platelet adenylyl cyclase to stimulation by
      prostaglandin E1.

PMID- 7648797
TI  - The genetic contribution to disease pathogenesis in childhood diabetes is
      greatest in the very young.
AB  - Epidemiological data are presented to support the hypothesis that the genetic
      contribution to disease pathogenesis in childhood onset diabetes is greatest in
      those presenting at a very early age. Analysis of family data from two national
      surveys of childhood onset Type 1 (insulin-dependent) diabetes (1988 in under
      15s: 1992 in under 5s) reveals that children developing diabetes between the ages
      1 and 2 years are significantly more likely to have a parental history of Type 1
      diabetes than older children. It is proposed that compared with other children,
      those with very early onset diabetes have either a greater genetic and smaller
      environmental contribution to the initiation of the autoimmune process leading to
      Type 1 diabetes: or inherited HLA alleles associated with a more fulminant
      autoimmune mediated Beta-cell destruction once the process is initiated.

PMID- 7648798
TI  - The neuronal toxic factor in serum of type 1 diabetic patients is a complement
      fixing autoantibody.
AB  - Type 1 diabetes is an autoimmune disease resulting in destruction of pancreatic
      beta cells. Many of the pancreatic beta cell autoantigens are also neuronal cell
      components. Using adrenergic neuroblastoma cells, we have previously demonstrated
      that humoral mechanisms may contribute to the development of diabetic neuropathy
      in Type 1 patients. We hypothesize that the toxic factor in Type 1 diabetic serum
      is an immunoglobulin. When neuroblastoma cells were exposed to immunoglobulins
      precipitated from serum of Type 1 diabetes patients with neuropathy, cell growth
      was significantly inhibited by day 5 (3.8 +/- 2.4 x 10(5) cells) compared to
      cells cultured with immunoglobulins from control (8.2 +/- 2.3 x 10(5) cells) or
      Type 2 diabetic serum (7.0 +/- 3.0 x 10(5) cells). The inhibitory effect (3.2 +/-
      0.9 x 10(5) cells) could be removed from Type 1 diabetic serum by affinity
      precipitation with protein A-agarose (8.0 +/- 0.8 x 10(5) cells). Mild heat
      denaturing of the serum reversed the inhibitory effect (3.8 +/- 0.9 vs 1.4 +/-
      1.4 x 10(5) cells), indicating a requirement for complement. Immunofluorescent
      labelling with anti-IgG secondary antibody of cells exposed to Type 1 diabetic
      serum indicated recognition of a membrane-bound antigen. The studies in this
      report support the hypothesis that autoimmune neuronal destruction may contribute
      to the development of diabetic autonomic neuropathy in patients with Type 1
      diabetes.

PMID- 7648799
TI  - Glomerular charge selectivity in type 1 (insulin-dependent) diabetes mellitus.
AB  - Glomerular charge selectivity was assessed using the ratio of the clearance of
      pancreatic isoamylase to the clearance of the more anionic salivary isoamylase
      (CPAm/CSAm) in 12 normal subjects and 50 patients with Type 1 diabetes: 13 with
      normal albumin excretion and short duration of diabetes (< 5 years), 15 with
      normal albumin excretion and long duration of diabetes (> 15 years), 13 with
      microalbuminuria, and 9 with clinical nephropathy. None had serum creatinine >
      200 mumol l-1. There were no significant differences in CPAm/CSAm between the
      normal subjects and the two groups of normoalbuminuric patients with Type 1
      diabetes. CPAm/CSAm was significantly lower in diabetic patients with
      microalbuminuria or clinical nephropathy than in normoalbuminuric patients with
      Type 1 diabetes. When the 37 patients with normoalbuminuria and long-standing
      diabetes, microalbuminuria, and nephropathy were considered together, there was a
      significant negative correlation between CPAm/CSAm and albumin excretion rate (rs
      = 0.71, p < 0.001). Progressive impairment of glomerular charge selectivity at
      the molecular size of amylase (molecular mass 56 kDa) accompanies increasing
      albuminuria in Type 1 diabetes.

PMID- 7648800
TI  - Effects of glucose and SNK-860, an aldose reductase inhibitor, on the polyol
      pathway and chemiluminescence response of human neutrophils in vitro.
AB  - An in vitro incubation study was conducted to investigate whether increased
      activity of the polyol pathway in human neutrophils under diabetic conditions
      resulted in a decrease of superoxide anion produced by NADPH oxidase on the
      membrane of neutrophils. Lucigenin-enhanced chemiluminescence (CL) to phorbol
      myristate acetate as respiratory burst and sorbitol levels in neutrophils after
      incubation with glucose and an aldose reductase (AR) inhibitor, SNK-860 (SNK)
      were measured. Sorbitol levels increased from 0.210 +/- 0.029 nmol 10(7) cells-1
      in 5 mmol l-1 glucose to 0.446 +/- 0.036 nmol 10(7) cells-1 in 40 mmol l-1
      glucose, while CL decreased from 0.542 +/- 0.034 cpm cell-1 in 5 mmol l-1 glucose
      to 0.430 +/- 0.018 cpm cell-1 in 40 mmol l-1 glucose. The addition of 10 mumol l
      1 SNK normalized the increased sorbitol levels in neutrophils exposed to 40 mmol
      l-1 glucose and improved, but did not normalize, the decrease in CL induced by 40
      mmol l-1 glucose (p < 0.001). Galactose (40 mmol l-1) also reduced CL, which was
      improved by the addition of SNK (p < 0.01). These results suggest that impaired
      respiratory burst induced by high-glucose concentrations is caused by competition
      for NADPH resulting from increased polyol pathway activity and/or glycation and
      that an AR inhibitor may be capable in part of preventing increased
      susceptibility to infection in diabetic patients.

PMID- 7648801
TI  - Epidemiology of diabetes mellitus in the elderly in northern Greece: a population
      study.
AB  - This population based study was undertaken to ascertain the overall prevalence of
      diabetes mellitus (DM) and impaired glucose tolerance (IGT) in the elderly using
      the WHO criteria. The role of obesity in the development of DM or IGT has been
      investigated for both sexes per decade of age. Furthermore the potential for DM
      to increase with age, as has been suggested before, has been evaluated using the
      IGT as a proportion of total glucose intolerance (IGT/TGI) for the same parts of
      the tested sample. From the 647 persons registered as elderly people in a small
      town in northern Greece (total population 5875 people), 66 persons did not
      participate in this survey. Fifty-six subjects (9.7%) had previously diagnosed
      DM. The remainder were tested using fasting blood glucose measurements or an oral
      glucose tolerance test (OGTT). The prevalence of previously undiagnosed DM
      according to fasting blood glucose values or after 2 h of 75 g load values was
      10.1% and 9.3%, respectively. Thus the overall prevalence of DM was 29.1% and of
      IGT was 15.1%. These data support an increased frequency of DM (65% previously
      undiagnosed) and IGT in the elderly, whereas this population's susceptibility
      seems to decline in the older groups for both sexes. Obesity remains a risk
      factor for DM and IGT particularly among the younger groups although its role has
      been found to decline with age.

PMID- 7648802
TI  - Energy expenditure in type 2 diabetic patients on metformin and sulphonylurea
      therapy.
AB  - Insulin and sulphonylurea therapies have both been reported to cause weight gain
      in Type 2 diabetic patients whereas metformin does not have this adverse effect.
      The mechanism for this difference is unclear. We have investigated in a cross
      over study the effect of sulphonylurea and metformin therapy on energy
      expenditure and body composition in 10 Type 2 diabetic patients (7 females, 3
      males) of various weights (mean body mass index 33.4 (SD 7.6 kg m-2)). Free
      living total energy expenditure was measured over 14 days by the doubly labelled
      water method adjusted for urinary glucose energy losses and resting energy
      expenditure by ventilated hood indirect calorimetry. Overall, total energy
      expenditure (12.88 +/- 4.17 vs 13.1 +/- 3.69 MJ 24 h-1) and resting metabolic
      rate (7.30 +/- 1.75 vs 7.23 +/- 1.74 MJ 24 h-1) were similar on metformin and
      sulphonylurea therapy, respectively. When adjusted for differences in fat free
      mass, resting metabolic rate on sulphonylurea therapy was slightly but
      significantly lower (mean difference -5.5 kJ 24 h-1 kg-1, 95% CI -1.2, -9.9 kJ 24
      h-1 kg-1, p < 0.05). Fat free mass also increased significantly by 1.3 kg (95% CI
      0.4, 2.4 kg, p < 0.05) when on sulphonylurea therapy, thus compensating for the
      lower resting metabolic rate per kg fat free mass to leave overall resting
      metabolic rate unchanged compared to metformin therapy. We also investigated the
      effect of adding metformin to six Type 2 diabetic patients already on insulin.
      This did not lead to any measurable changes in any of the components of energy
      expenditure.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7648803
TI  - The comparison of four weight reduction strategies aimed at overweight diabetic
      patients.
AB  - Four weight reduction strategies were investigated in a diabetic population who
      previously had shown little motivation to lose weight. Some 409 patients, body
      mass index 28-45 were invited to participate. Only 51% replied, although 22
      patients (5.4%) lost > 3 kg by invitation alone. The study comprised 159
      patients, randomly allotted to either regular clinic visits, behavioural group
      therapy, dexfenfluramine (30 mg d-1 for initial 3 months) or combined home and
      clinic visits. A further 58 patients were monitored as controls. At 3 months the
      best weight loss (intention to treat) was achieved using dexfenfluramine with
      mean weight losses of 1.6, 1.2, 3.4, and 1.7 kg, respectively, in each group. At
      1 year weight losses were similar (1.2, 1.8, 2.8, 1.2 kg, respectively) but
      contrasted with a mean 1.2 kg weight gain in the controls. Some 38% lost > 3 kg
      on dexfenfluramine compared to 19-23% for the others. In those who completed the
      study, weight loss was similar with behavioural therapy (3 kg) or dexfenfluramine
      (3.2 kg). We conclude that intensive dietetic efforts can reverse the weight
      increase in the diabetic population although weight loss is minimal.
      Dexfenfluramine was most effective in the short term, behavioural therapy useful
      long term but only in those who remained within the group; home visits offered no
      advantage.

PMID- 7648805
TI  - A report on the use of technician ophthalmoscopy combined with the use of the
      Canon non-mydriatic camera in screening for diabetic retinopathy in the
      community.
AB  - This paper describes a general practice based diabetic retinopathy screening
      service employing a technician trained in direct and indirect ophthalmoscopy and
      taking photographs with a Canon CR3 45 NM non-mydriatic polaroid camera analysed
      by a consultant ophthalmologist to provide a comparison with the screener's
      opinion. Prospective data is presented from the first 1050 patients screened for
      diabetic retinopathy in the Exeter Health Authority area. Analysis of data
      collected showed a prevalence of diabetic retinopathy in the screened population
      of 27%, 14% previously undetected with a 0.5% prevalence of sight-threatening
      retinopathy. There was almost complete agreement between ophthalmoscopy findings
      and the consultant analysis of photographs. Screening costs were calculated at
      10.38 pounds per patient screened. A specially trained non-medically qualified
      technician can provide a good quality cost-effective screening service for
      diabetic retinopathy within a primary care setting.

PMID- 7648804
TI  - A study of fluoxetine in obese elderly patients with type 2 diabetes.
AB  - In order to establish the safety and efficacy of fluoxetine in subjects over 60
      years of age with Type 2 diabetes, a randomized, double-blind, parallel study of
      30 obese subjects was undertaken, comparing the use of fluoxetine 60 mg daily
      with placebo. Subjects were diet controlled with an HbA1 < 14% (reference range 6
      9%) and BMI > 29 kg m2. Those taking fluoxetine had a median weight loss of 2.6
      kg at 3 months (p < 0.001) and 3.9 kg at 6 months (p < 0.02), compared with
      weight loss in the placebo group of 0.1 kg and 0.0 kg at 3 and 6 months,
      respectively. Improved glycaemic control was also demonstrated in the fluoxetine
      group compared with placebo, initial HbA1 levels of 8.0% vs 8.7% (NS) falling at
      4 months by 0.9% (p < 0.02) and at six months by 0.9% (p < 0.02). No sustained
      improvement in fasting blood glucose levels was demonstrated. Reporting of
      adverse events was similar in both groups. Fluoxetine in the short term aids
      weight loss and improves glycaemic control without a significant increase in
      adverse events in elderly Type 2 diabetic subjects.

PMID- 7648806
TI  - Use of thrombolysis for acute myocardial infarction in the presence of diabetic
      retinopathy in the UK, and associated ocular haemorrhagic complications.
AB  - Diabetic retinopathy is still regarded as a relative contraindication to the use
      of thrombolysis for myocardial infarction because of a perceived risk of
      intraocular haemorrhage. However, this complication has rarely been reported and
      the risk may be too small to justify withholding thrombolysis. A questionnaire
      survey was therefore conducted of members of the Medical and Scientific Section
      of the British Diabetic Association (BDA), to ascertain the exclusion criteria
      applied to the use of thrombolysis in patients with diabetic retinopathy in the
      UK and to identify any related ocular haemorrhagic complications. Replies were
      received from 128 physicians in 107 centres. Exclusion criteria applied were: any
      retinopathy 7 (5%), proliferative retinopathy and recent vitreous or pre-retinal
      haemorrhage 74 (58%), recent vitreous haemorrhage only 25 (20%), thrombolysis
      given regardless of retinopathy 22 (17%). No cases of intraocular haemorrhage
      following thrombolysis in diabetic myocardial infarction patients were
      identified. The risks of this complication appear to be very small and probably
      do not justify withholding thrombolytic therapy from diabetic patients with most
      forms of retinopathy, including proliferative.

PMID- 7648807
TI  - Abnormal insulin treatment behaviour: a major cause of ketoacidosis in the young
      adult.
AB  - Diabetic ketoacidosis occurs more frequently in the young adult population than
      in any other age group. In a 3-year retrospective casenote review of all patients
      admitted with ketoacidosis to this hospital, we have defined the clinical
      characteristics of ketoacidosis in this age group. Young adults (< 25 years) had
      worse preceding glycaemic control (median HbA1 14.6 vs 10.1%, p = 0.0001) and
      more frequent episodes of ketoacidosis in the previous 5 years (3 vs 0, p =
      0.0001) than older adults (> 25 years); on admission they had lower blood urea
      concentrations (p = 0.0001) and had a lower incidence of systolic hypotension (6%
      vs 32%, p = 0.007). There were fewer complications of ketoacidosis in the young
      adults, and the duration of hospital stay was less than that in the older age
      group (4 vs 8 days, p = 0.0003). Young adults were less likely to have a proven
      underlying infective or other organic precipitant for ketoacidosis, but were
      investigated and treated in a similar way to older adults. Insulin error or
      manipulation was identified in 42% of young adults; abnormal insulin treatment
      behaviour is likely to be the major cause of ketoacidosis in this age group.

PMID- 7648808
TI  - Factitious hypoglycaemia documented by a modified assay for the measurement of
      plasma sulphonylurea.
AB  - Two cases of factitious hypoglycaemia due to intentional or inadvertent intake of
      glipizide by non-diabetic subjects were identified through the measurement of
      this sulphonylurea in plasma by a modified assay procedure.

PMID- 7648809
TI  - Educating the diabetes care professionals in eastern Europe: a Bulgarian
      experience.
AB  - The first educational course for 30 medical doctors and 16 nurses, engaged in
      outpatient diabetes care in Bulgaria, was carried out with the aim of assessing
      the existing level of knowledge of diabetes, to implement a training programme
      matching the assessed needs, and to evaluate the efficiency of the education
      delivered. The initial level of knowledge was assessed by an anonymous pre-test
      questionnaire on general issues of diabetes care. After 5 days of training, a
      post-test questionnaire was administered which included more specific questions
      on matters that had been taught during the course. The results of the pre-test
      showed that, on average, 60.3 +/- 20.6 (SD) % of the doctors and 50.5 +/- 25.0%
      of the nurses gave correct answers. The results of the post-test were
      significantly improved (73.5 +/- 20.6% for the doctor and 70.8 +/- 23.5% for the
      nurses), although the post-test questionnaire had been expertly evaluated as more
      complex and specific. The analysis of the results allowed us to draw general
      conclusions regarding the educational needs, the optimal structure, and
      implementation of such training courses in the specific conditions of Bulgaria.
      Some of the results and conclusions might be useful for other countries from
      Central and Eastern Europe in their efforts to promote successful diabetes
      education programmes.

PMID- 7648810
TI  - Retinopathy in Maltese type 2 diabetic patients.
AB  - Since diabetes is a major health problem in Malta a study was conducted to gain a
      better insight into one of its most common complications, that of retinopathy. A
      random sample of 200 cases of adult onset diabetes with retinopathy who attended
      the main hospital's diabetes clinic was assessed by an experienced
      ophthalmologist. Non-proliferative retinopathy was subdivided into three degrees
      of severity according to the number of microaneurysms, haemorrhages, exudates,
      and intraretinal microvascular abnormalities present while proliferative
      retinopathy included also advanced eye disease. Data on medical and family
      histories was gathered from personal interrogation and counterchecked from
      hospital files. A medical examination searched for other concomitant disease. The
      124 females and 73 males were similarly aged with a mean of 59.5 +/- 11.5 years.
      The mean age at onset of diabetes was 44.4 +/- 7.9 years: no significant
      differences were seen between the grades of retinopathy or the sexes. Onset of
      eye disease was first detected at a mean age of 56.9 +/- 7.0 years. The great
      majority (82%) of retinopathy cases occurred after 10 years of diabetes. Males
      appeared to develop eye disease (especially non-proliferative) at a younger age
      (53.4 +/- 7.6 vs 58.9 +/- 6.6 years, p < 0.01) and after a shorter duration of
      diabetes (10.1 +/- 6.6 vs 14.0 +/- 7.8 years, p < 0.001) than females. Severity
      of retinopathy was strongly associated (p < 0.001), in females rather more than
      in males, with poor glycaemic control, use of insulin, presence of proteinuria
      and decreasing vision; and less markedly (p < 0.01) with duration of diabetes of
      more than 10 years, neuropathy and glaucoma.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7648811
TI  - A reproducibility study of technetium-99m macroaggregated albumin foot perfusion
      imaging in patients with diabetes mellitus.
AB  - The reproducibility of Technetium-99m macroaggregated albumin (99mTc-MAA) foot
      perfusion imaging was assessed in 14 diabetic patients with foot ulcers.
      Bilateral femoral intra-arterial injections of 99mTc-MAA were administered and
      the feet imaged with a gamma camera. Patients returned 1 week later for a repeat
      study. The scans of 10 patients including one unilateral amputee were evaluated.
      Of these 19 limbs there were 4 failed injections (21%). The remaining 15
      completed repeat studies were analysed both subjectively and semiquantitatively
      by 2 different observers who were blind to the patient's name and scan date.
      Subjectively the images of each individual were similar with reports highlighting
      the same abnormalities. Semiquantitatively areas of increased uptake on both
      images were significantly correlated for each individual (Pearson's Rho
      correlation coefficient = 0.96, r2 = 0.92, p < 0.0001) as were areas of poor
      uptake reported, reflecting decreased tissue perfusion (Pearson's Rho = 0.93, r2
      = 0.86, p < 0.0001). There were no side-effects. 99mTc-MAA has proven to be a
      safe, generally acceptable, and reproducible technique for assessing tissue
      perfusion in the extremities which provides an accurate means of differentiating
      viable from non-viable tissue in patients with foot ulcers.

PMID- 7648813
TI  - Do insulin-treated diabetic patients use an injection-meal-interval in daily
      life?

PMID- 7648812
TI  - Are islet cell antibodies of prognostic value in obese subjects with late-onset
      diabetes?

PMID- 7648814
TI  - Exactech blood glucose meter.

PMID- 7648815
TI  - Postprandial triglyceridaemia.

PMID- 7648816
TI  - Can the use of lists improve the proportion of concerns addressed in the
      consultation?

PMID- 7648817
TI  - The International Diabetes Federation: the next millennium.

PMID- 7648819
TI  - Non-insulin-dependent diabetes mellitus and islet B-cell mitochondrial
      glycerophosphate dehydrogenase deficiency.
AB  - A deficient activity of the mitochondrial FAD-linked glycerophosphate
      dehydrogenase (m-GDH) in the pancreatic islet B-cell may represent a contributing
      factor in the pathogenesis of non-insulin-dependent (Type 2) diabetes. This
      enzyme controls circulation in the glycerol phosphate shuttle and, hence, plays a
      key role in the B-cell glucose-sensing device. An impaired activity of this
      enzyme in pancreatic islets was documented in several, but not all, animal models
      of inherited or acquired non-insulin-dependent diabetes. Enzymatic studies
      conducted in lymphocytes or islets from diabetic patients, as well as a search
      for possible mutations of the m-GDH gene, were recently undertaken to extend
      these observations to human subjects.

PMID- 7648818
TI  - Drugs on the horizon for treatment of type 2 diabetes.
AB  - The only new pharmaceutical therapy for Type 2 (non-insulin-dependent) diabetes
      that has become available for clinical use in the last 40 years is the alpha
      glucosidase inhibitor, acarbose, which reduces postprandial glucose levels by
      retarding digestion of complex carbohydrates in the gut. It has proved difficult
      to find other new metabolically active drugs that lack toxicity. Agents that
      reduce insulin resistance include the thiazolidinediones, which are very
      effective in animals. Of these, the only one that has been maintained in clinical
      evaluation appears from preliminary data to have an effect that although still
      useful, is not greater than that reported for current oral agents. Agents that
      reduce non-esterified fatty acid levels by inhibiting lipolysis, thereby allowing
      increased peripheral uptake of glucose, have so far given minimal reduction in
      glycaemia. The development of fatty acid oxidation inhibitors to reduce
      gluconeogenesis in the liver has been hampered by toxicity, but additional new
      agents are being studied. The most promising new approach for enhancing insulin
      secretion has been suggested by the demonstration that pharmacological doses of
      GLP-1 (7-36 amide), a natural enteric incretin hormone, improves pancreatic beta
      cell and alpha-cell sensitivity to glucose and can induce normal basal glucose
      levels in diabetic man. The future development of GLP-1 agonists will be of great
      interest. This is timely as other insulin secretogogues, such as alpha 2
      adrenergic blockers have proved relatively ineffective. Anti-obesity agents would
      in theory be beneficial, but have either had limited efficacy or have been
      avoided because of concern about long-term safety. Until new pharmaceutical
      agents become available, if near-normal glycaemia is to be achieved, many more
      Type 2 diabetic patients will need insulin therapy. When full insulin replacement
      therapy is not feasible, reducing the fasting blood glucose level towards normal
      with a single daily basal insulin supplement, either alone or in combination with
      oral agents, could become a more widely used therapy.

PMID- 7648820
TI  - The natural course of microalbuminuria in insulin-dependent diabetes: a 10-year
      prospective study.
AB  - The purpose of this study was to describe the clinical course in patients
      followed right from the onset of microalbuminuria to the development of diabetic
      nephropathy. A 10-year prospective follow-up of 209 consecutive normotensive
      insulin-dependent diabetic patients with normal urinary albumin excretion (UAE <
      30 mg 24 h-1), age 34 (18-50) years and duration of diabetes 17 (10-30) years was
      performed. Twenty-four-hour urinary albumin excretion was measured every 4
      months, glycated haemoglobin and supine blood pressure was measured annually. Two
      hundred (96%) patients completed 10 (range 5-10) years follow-up. Twenty-nine
      (15%) patients developed persistent microalbuminuria (UAE 30-300 mg 24 h-1).
      Eight of these have progressed to nephropathy and one had died of diabetic
      nephropathy. Multiple stepwise logistic regression analysis demonstrated baseline
      urinary albumin excretion (p = 0.0016) and glycated haemoglobin (p = 0.0014) but
      not blood pressure as predictors of development of microalbuminuria within the
      following 10 years. The median annual increase in urinary albumin excretion was
      27 (range 17-65) % in the 29 patients developing microalbuminuria. The median
      duration from onset of microalbuminuria to development of nephropathy was 7
      years. The prevalence of patients receiving antihypertensive treatment (BP >
      140/90 mmHg) increased from 10% at onset of microalbuminuria to 45% 4 years after
      onset of microalbuminuria. The prevalence of patients with proliferative
      retinopathy increased from 7% at onset of microalbuminuria to 28% 4 years after
      onset of microalbuminuria.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7648821
TI  - Urinary albumin excretion in a population based cohort.
AB  - In order to compare a 1-h daytime urine specimen collection with a timed
      overnight collection, as well as different ways of expressing urinary albumin
      excretion: (urinary albumin excretion rate (UAE), urinary albumin concentration
      (UAC), and urinary albumin creatinine ratio (UACR)), a population of 922 people
      of whom 35 had diabetes was examined. The median age was 47 (range 26-65) years.
      The results of the different ways of collecting urine specimens and the different
      expressions of urinary albumin excretion were related to known cardiovascular
      risk factors. The daytime collection showed higher values of urinary albumin
      excretion than the overnight collections. Systolic blood pressure was an
      important risk factor correlated to UAE and UACR in the day as well as the
      overnight collection, followed by HbA1C in the total group and by BMI in the non
      diabetic group. UAC showed significant relation to triglycerides and HDL
      cholesterol. In conclusion, urinary albumin in a 1-h daytime collection showed a
      similar correlation to cardiovascular risk factors as the excretion of albumin in
      overnight collected urine. Follow-up studies are needed to compare day
      collections of urine as predictors of cardiovascular disease and early death with
      overnight collections.

PMID- 7648822
TI  - The relationship between pregnancy and long-term maternal complications in the
      EURODIAB IDDM Complications Study.
AB  - Pregnancy is believed to exacerbate diabetes complications, although the degree
      to which this occurs, and the advice that should be given to women contemplating
      pregnancy is unclear. We examined 776 nulliparous and 582 parous women with Type
      1 diabetes from a cross-sectional study performed in 31 European centres.
      Glycaemic control was better in parous women. Age and duration adjusted
      prevalence of microalbuminuria was similar in parous and nulliparous women, but
      macroalbuminuria was lower in parous women (6% versus 10%, p < 0.0001).
      Prevalence of all retinopathy was lower in parous women (34% in women who had two
      or more pregnancies, 45% in women who had one), compared with 48% in nulliparous
      women (chi 2 for trend = 47.1, p < 0.0001). Proliferative retinopathy was lower
      in parous (8% and 7%, respectively) compared with nulliparous women (16%, chi 2
      for trend = 52.2, p < 0.0001). These differences persisted when adjusted for
      glycaemic control. Excluding referrals for pregnancy, parous women were more
      likely to have been referred to the diabetes clinic with complications than
      nulliparous women (p = 0.001). It is unlikely that our findings can be explained
      by women with complications being advised against pregnancy, or by the better
      glycaemic control in parous women. Equivalent levels of microalbuminuria and
      background retinopathy in parous and nulliparous women suggests that pregnancy
      may not exacerbate these early complications.

PMID- 7648823
TI  - The frequency of known diabetes, hypertension and ischaemic heart disease in
      affluent and poor urban populations of Karachi, Pakistan.
AB  - The high frequency of diabetes mellitus and coronary artery disease among people
      of South Asian extraction living in the West is well established. The prevalence
      of these disorders in Southern Asia is less certain. No previous attempt has been
      made to estimate their occurrence in Pakistan. In order to compare the prevalence
      of known diabetes mellitus, hypertension and ischaemic heart disease between
      affluent and poor urban communities in Pakistan, a survey of consecutive
      households was undertaken in a relatively prosperous and a poor area in Karachi.
      Information was obtained on 4232 adults evenly distributed between the two areas.
      Body weight and height were measured in 199 healthy subjects at the two sites.
      The prevalence of known diabetes in the affluent population was 4.5%,
      significantly higher than 1.8% in the poor area (p < 0.001). A maximal prevalence
      of 25% was seen in the affluent community aged 55-64. Diabetes was more common in
      females in both populations. The overall prevalence of hypertension was similar
      in the two areas although significantly more frequent in the middle aged and
      affluent. A history of ischaemic heart disease occurred in 1.9% of the affluent
      and 0.6% of the poor (p = 0.003). Healthy subjects were heavier and more obese in
      the richer community. Thus the susceptibility of South Asian populations to
      diabetes and ischaemic heart disease is also apparent in an affluent segment of
      Pakistani society. The phenomenon is not attributable simply to urbanization.
      Obesity is probably an important contributory factor. The economic implications
      for developing South Asian countries are serious.

PMID- 7648824
TI  - Coagulation activation in type 2 diabetes mellitus: the higher coronary risk of
      female diabetic patients.
AB  - Thrombophilia in diabetic patients is a well-recognized phenomenon which
      constitutes an additional risk of coronary heart disease. This study included
      1980 ethnic Chinese people (835 male, 1145 female); age range: 45 to 69 years,
      including 280 Type 2 diabetic patients (male 125, female 155). Haemostatic
      parameters measured were fibrinogen, prothrombin time, activated partial
      thromboplastin time (APTT), factor VIIc, factor VIIIc, antithrombin III, and
      plasminogen. Compared with a control group, male diabetic patients showed
      significantly shorter APTT (25.6 +/- 3.7 vs 27.5 +/- 3.6 s, p < 0.001), and
      elevated factor VIIIc (171.1 +/- 77.48 vs 131.16 +/- 52.23%, p < 0.0001), whereas
      female diabetic patients showed significantly shorter APTT (24.9 +/- 4.2 vs 26.5
      +/- 3.9 s, p < 0.001) and elevated fibrinogen (10.6 +/- 3.3 vs 9.8 +/- 2.6 mumol
      1(-1), p < 0.05), factor VIIc (150.4 +/- 68.7 vs 135.3 +/- 32.3%, p < 0.001),
      factor VIIIc (190.1 +/- 92.6 vs 141.1 +/- 62.4%, p < 0.0001), and plasminogen
      (140.3 +/- 41.9 vs 128.4 +/- 38.7%, p < 0.01). This study showed that Chinese
      diabetic patients had coagulation activation, and that female diabetic patients
      seemed to constitute a higher risk group for coronary heart disease than males.

PMID- 7648825
TI  - Longitudinal study of lipoprotein(a) in peripubertal children with insulin
      dependent diabetes.
AB  - We aimed to examine the longitudinal relationship between lipoprotein(a) and
      haemoglobin A1c, albumin excretion rate, and puberty in peripubertal children
      with insulin-dependent diabetes. A total of 114 patients aged 11.5 +/- 3.6 years
      (mean (SD)) were followed prospectively for 15.2 +/- 2.8 months. Lipoprotein(a),
      apolipoproteinB-100, haemoglobin A1c, mean overnight albumin excretion rate and
      Tanner stage were determined at the beginning and end of the study period.
      Lipoprotein(a) and apolipoproteinB-100 were measured using nephelometry. This
      method was correlated with radioimmunoassay and there was no significant change
      in mean bias during the study. Lipoprotein(a) fell significantly over time (214,
      (152, 276); 160 (84, 236) mg l-1 geometric mean (0.95 confidence intervals), p <
      0.001); apolipoproteinB-100 did not change. Lipoprotein(a) and apolipoproteinB
      100 did not differ in 233 cross-sectional controls of similar age. The change in
      lipoprotein(a) did not correlate with a small fall in haemoglobin A1c or with
      overnight albumin excretion rate, Tanner stage or insulin dose. Separate analysis
      of male and female patients and prepubertal and pubertal patients continued to
      show a significant fall in lipoprotein(a) independent of change in haemoglobin
      A1c or albumin excretion rate. Likewise, 53 patients with a change in haemoglobin
      A1c of greater than 1%, and 20 patients who progressed from normal albumin
      excretion rate to albumin excretion rate above the 95th centile, showed no
      relationship between lipoprotein(a) and haemoglobin A1c or albumin excretion
      rate. In conclusion, longitudinal changes in lipoprotein(a) do not relate to
      metabolic control or early changes in albuminuria in young patients with insulin
      dependent diabetes.

PMID- 7648826
TI  - The splanchnic circulation and postural hypotension in diabetic autonomic
      neuropathy.
AB  - Postural hypotension results from sympathetic failure to cause superior
      peripheral vasoconstriction. The importance of the splanchnic circulation was
      studied by measuring mesenteric artery blood flow with duplex Doppler scanning.
      Nine normal and 9 Type 1 diabetic controls were compared to 8 Type 1 patients
      with autonomic neuropathy whose pressure fell 40-113 mmHg (range) on tilting.
      Measurements were made supine and after vertical tilt, fasting without insulin
      and after a 550 kcal meal. Superior mesenteric artery diameter decreased on
      tilting in normal controls but not in diabetic control or neuropathy groups
      (supine vs tilted: controls. 6.3 +/- 0.9 to 5 +/- 0.9 mm, p = 0.004, diabetic
      controls: 6.0 +/- 0.6 to 6.0 +/- 1.0 mm, and neuropathy group: 6.4 +/- 0.9 to 5.6
      +/- 0.9 mm), but proportional blood flow changes were similar in all subjects
      (controls: 407 +/- 154 to 255 +/- 67 ml min-1 (-31%, p = 0.03), diabetic
      controls: 379 +/- 140 to 306 +/- 149 ml min-1 (-8%, p = 0.28), neuropathy group:
      639 +/- 371 to 435 +/- 142 ml min-1 (-23%, p = 0.10). Postprandially supine
      superior mesenteric artery flow increased in all subjects but this did not affect
      the degree of systolic blood pressure drop on tilting (fasting vs postprandial
      blood flow: controls: 407 +/- 154 to 775 +/- 400 ml min-1 (p = 0.04), diabetic
      controls: 379 +/- 140 to 691 +/- 262 ml min-1 (p = 0.01), neuropathy group: 639
      +/- 371 to 943 +/- 468 ml min-1 (p < 0.06)). The similarity of superior
      mesenteric artery responses to tilting in the three groups, and the lack of
      exacerbation of postural hypotension in the presence of postprandial hyperaemia
      indicates that control of splanchnic blood flow is less important in the
      aetiology of diabetic autonomic postural hypotension than previously thought.

PMID- 7648828
TI  - An optical practice based diabetic eye screening programme.
AB  - In many cases, blindness due to diabetic retinopathy can be prevented provided
      treatment with laser photocoagulation is used at the correct time. A screening
      programme is required to identify cases of sight threatening retinopathy. An
      optical practice based diabetic eye screening programme has been established in
      Dorset. The optometrist undertaking the examination is paid a fee. The findings
      are recorded on a coded form and sent to the hospital diabetologist who recalls
      positive cases. Seventy-six optical practices have joined the scheme and 3224
      patients have been screened in the first 6 months (Dorset population 655,000). In
      the Poole area (population 230,000), 1922 patients were screened and 129 (6.7%)
      were recalled in 6 months. Outcome of 3 months screening, identified 59 recalls.
      Referral to the opthalmologist was made in 15 cases for potentially sight
      threatening retinopathy, 14 cases were followed in the diabetic clinic for
      significant background retinopathy, and 24 cases were returned to the annual
      screening in the optical practices. Six cases where the patients either failed or
      were unable to attend were reviewed by the GP. An optical practice based diabetic
      eye screening programme has been successful in screening a large number of
      patients.

PMID- 7648827
TI  - Importance of early insulin levels on prandial glycaemic responses and
      thermogenesis in non-insulin-dependent diabetes mellitus.
AB  - To examine the effect of different profiles of insulin administration on
      glycaemia and thermogenesis, we studied 10 subjects with mild non-insulin
      dependent diabetes mellitus on four occasions after a standard mixed meal: (1)
      with no supplementary insulin (control), (2) with intravenous insulin (1.8U over
      15 min = short), (3) as for short but extended over 30 min to simulate the normal
      initial rise in portal vein insulin levels (medium), (4) as for medium with
      additional insulin to normalize the profile from 30-60 min (3.6U over 60 min,
      long). All studies in which supplemental insulin was administered lowered the
      integrated glucose response above baseline versus the control study (short 76%,
      medium 71%, and long 56% of control, p = 0.003). The insulin infusions also
      increased the non-protein respiratory quotient in the first hour following the
      meal (0.82 +/- 0.01 (control) vs 0.87 +/- 0.01 (short), 0.86 +/- 0.01 (medium)
      and 0.87 +/- 0.01 (long), p = 0.003) and augmented thermogenesis (7.6 +/- 1.5
      (control) vs 10.5 +/- 2.9 (short), 13.0 +/- 1.9 (medium) and 13.2 +/- 2.8%
      (long), p = 0.02). Total integrated insulin area above baseline was significantly
      greater in the long study (short 121, medium 111 vs long 179% of control, p =
      0.02). Thus the greatest glycaemic benefit in relation to insulinaemia was
      obtained with the two shorter insulin infusions (short and medium). In
      conclusion, this study confirms the role of early prandial insulin secretion (or
      delivery) in limiting prandial glycaemia in NIDDM and increasing thermogenesis
      and highlights the pivotal role of the timing of elevation of insulin levels in
      modulating hyperglycaemia and hyperinsulinaemia.

PMID- 7648829
TI  - Comparative analysis of patency, limb salvage and survival in diabetic and non
      diabetic patients undergoing infrainguinal bypass surgery.
AB  - In 92 diabetic and 175 non-diabetic patients undergoing 336 femoropopliteal or
      femorodistal bypass procedures, 1- and 3-year cumulative life-table patency, limb
      salvage, and survival rates were comparatively analysed. The peroperative
      mortality rate was significantly higher in diabetic patients (5% compared to
      1.4%, p < 0.001). The cumulative graft patency rates were 61% at 12 months and
      46% at 36 months in diabetic patients compared to 64 and 52% in non-diabetic
      patients. Significantly better patency rates were observed in limbs with good
      runoff compared to limbs with poor runoff in both groups. The limb salvage rates
      at 3 years were 70% in diabetic patients and 62% in non-diabetic patients. The
      survival rate at 3 years was significantly lower in diabetic patients, 62%
      compared to 86% in non-diabetic patients. Diabetic patients with poor runoff
      demonstrated a significantly lower survival rate after 36 months compared to
      diabetic patients with good runoff (48% and 74%, respectively). The results of
      this study demonstrate that the early and intermediate patency and limb salvage
      rates are similar in diabetic and non-diabetic patients. On the other hand the
      survival rate in diabetic patients, especially in those with poor distal runoff,
      is significantly lower than non-diabetic patients.

PMID- 7648830
TI  - Nesidioblastosis in an elderly patient.
AB  - We report an 84-year-old woman with hypoglycaemia and hyperinsulinaemia caused by
      diffuse nesidioblastosis. This is the oldest case of nesidioblastosis so far
      recorded. The case illustrates some of the difficulties in diagnosing
      inappropriate hyperinsulinaemia and the benefits of surgery, even in old age.
      Hypoglycaemia should be considered in patients with variable mental function.

PMID- 7648831
TI  - Mortality and outcome of insulin-dependent diabetes in Soweto, South Africa.
AB  - Sixty-four insulin-dependent (Type 1) diabetic patients (IDDM) in Soweto, South
      Africa were followed over a 10-year period. Patients were assessed in 1982 and
      again in 1992. There were 10 deaths (16%), half of which were due to renal
      failure. Ketoacidosis, hypoglycaemia, and sepsis accounted for the rest. At the
      10-year follow-up mean age (+/- SD) was 32.4 +/- 5.0 years and diabetes duration
      13.6 +/- 2.6 years. Retinopathy affected 52%, peripheral neuropathy 42%, and
      nephropathy 28% (all significantly increased from the 1982 assessment).
      Microalbuminuria and autonomic neuropathy were also common. Serum cholesterol was
      over 6.5 mmol l-1 in 19%, hypertension affected 22%, and 28% were cigarette
      smokers; though no patient had evidence of macroangiopathy. We conclude that IDDM
      in South Africa is associated with excess mortality, a significant proportion of
      which is related to nephropathy. Diabetes of long duration is now not uncommon in
      South Africa, and although diabetic complications frequently occur, most patients
      have good life quality and freedom from large vessel disease.

PMID- 7648832
TI  - Detection of Borrelia burgdorferi DNA by polymerase chain reaction in the urine
      and breast milk of patients with Lyme borreliosis.
AB  - Current laboratory diagnosis of Lyme borreliosis relies on tests for the
      detection of antibodies to Borrelia burgdorferi with known limitations. By using
      a simple extraction procedure for urine samples, B. burgdorferi DNA was amplified
      by a nested PCR with primers that target the specific part of the flagellin gene.
      To control possible inhibition of the enzyme (polymerase), a special assay using
      the same primers was developed. We examined 403 urine samples from 185 patients
      with skin manifestations of Lyme borreliosis. Before treatment, B. burgdorferi
      DNA was detected in 88 of 97 patients with Lyme borreliosis. After treatment, all
      but seven patients became nonreactive. Six of these seven persons suffered from
      intermittent migratory arthralgias or myalgias, and one from acrodermatitis
      chronica atrophicans. Two of 49 control patients with various dermatologic
      disorders and none out of 22 presumably healthy persons were reactive in the PCR.
      In addition to urine, breast milk from two lactating women with erythema migrans
      was tested and also found reactive. Borrelia burgdorferi DNA can be detected with
      high sensitivity (91%) by a nested PCR in urine of patients with Lyme
      borreliosis. In addition, this test can be a reliable marker for the efficacy of
      treatment.

PMID- 7648833
TI  - Comparison of three methods of antifungal susceptibility testing with the
      proposed NCCLS standard broth macrodilution assay: lack of effect of phenol red.
      National Committee for Clinical Laboratory Standards.
AB  - Three microtiter plate adaptations of the NCCLS proposed standard for antifungal
      susceptibility testing were evaluated and compared to the NCCLS broth
      macrodilution method. Thirteen different fungi, including yeasts and moulds were
      studied. The first microtiter based method was performed exactly as described for
      the tube dilution assay, with the exception of performance of the assay in 100
      microliter in wells of the microtiter plate. The second assay was the same as the
      first, except for the deletion of phenol red from the RPMI 1640. The third
      microtiter assay was based on the reduction of the formazan dye, XTT, after only
      24 hours of incubation. All three microtiter methods compared favorably with the
      macrodilution method, when visually read after either 24 or 48 hours of
      incubation. Minimum inhibitory concentrations obtained by the XTT assay were
      usually lower than those obtained by the methods requiring a visual end point
      determination. Results were reproducible and comparable to those obtained with
      the NCCLS method. We conclude that microtiter plate adaptation of the NCCLS
      proposed standard is feasible and the presence of phenol red does not alter the
      results with the drugs tested. A 24 hour assay using XTT may provide a quicker
      and more quantitative method of susceptibility testing of fungi. Further
      investigation of this approach is warranted.

PMID- 7648834
TI  - Validation of a modified Kirby-Bauer disk diffusion method for metronidazole
      susceptibility testing of Helicobacter pylori.
AB  - Triple antimicrobial therapy that includes metronidazole has been recommended as
      a first-line therapy for Helicobacter pylori because it has the highest
      eradication rates. However, resistance in H. pylori to metronidazole has been
      reported worldwide and its presence may reduce the efficacy of triple therapy.
      Various methods for testing H. pylori against metronidazole have been used
      including agar dilution, disk diffusion and the Etest but there has been little
      standardization of methods. One hundred isolates of H. pylori from different
      patients were tested for susceptibility to metronidazole by agar dilution, Etest
      and disk diffusion (5 micrograms disk). The agar dilution results confirmed the
      MIC susceptibility breakpoint to be < or = 8 micrograms/ml. Using this breakpoint
      there was close agreement (98%) between Etest and agar dilution results. For
      susceptible strains, MICs by E-test were generally one twofold dilution lower.
      Using the error-rate bounded method, agreement between disk diffusion zone
      diameter and MIC was 98% for agar dilution with breakpoints of > or = 12 mm and <
      or = 8 micrograms/ml and 100% for Etest with breakpoints of > or = 12 mm and < or
      = 8 micrograms/ml. The Etest discriminated better than agar dilution between
      susceptible and resistant strains and was simple to perform. The disk diffusion
      test is a reliable and cheaper alternative to the Etest with susceptibility being
      a zone diameter > or = 12 mm with a 5 micrograms disk. The prevalence of
      metronidazole resistance in this study was 40% by Etest.

PMID- 7648835
TI  - National survey of the in vitro spectrum of piperacillin-tazobactam tested
      against more than 40,000 aerobic clinical isolates from 236 medical centers.
AB  - Hospital microbiology laboratories from 41 states participated in a bacterial
      antimicrobial susceptibility study comparing in vitro results generated by the
      standardized disk diffusion method. Over 41,000 freshly isolated aerobic and
      facultative strains, representing all specimen types (except stools and urines),
      were tested for their susceptibility to piperacillin-tazobactam and 21 other
      antimicrobial agents. Enterococcus spp. was the second or third most common
      isolate from intraabdominal, gynecologic, and cutaneous infections, confirming
      its growing importance as a nosocomial pathogen. Escherichia coli was the most
      frequent isolate overall, despite the exclusion of urinary tract specimens from
      the study. Pseudomonas aeruginosa was the second most prevalent species, ranking
      first in frequency of recovery from lower-respiratory-tract specimens.
      Piperacillin-tazobactam was the most active beta-lactamase inhibitor combination
      tested against Gram-negative bacteria. Its activity against Gram-positive
      bacteria and Haemophilus influenzae was similar to that of ampicillin-sulbactam
      (95-97% susceptible). Imipenem and piperacillin-tazobactam displayed similar
      spectrums of activity against Gram-positive organisms and Haemophilus influenzae.
      Against Enterobacteriaceae, piperacillin-tazobactam and ceftazidime exhibited
      similarly wide spectrums of activity, but with some gaps, particularly among
      Enterobacter spp. and Citrobacter freundii. In this large-scale in vitro study,
      piperacillin-tazobactam and imipenem displayed the widest antimicrobial
      spectrums, inhibiting > 90% of all isolates tested.

PMID- 7648836
TI  - Comparative antimicrobial activity of piperacillin-tazobactam tested against more
      than 5000 recent clinical isolates from five medical centers. A reevaluation
      after five years.
AB  - Piperacillin combined with tazobactam at a fixed concentration (4 micrograms/ml)
      and a ratio (8:1) was tested against 5,029 aerobic isolates and 447 fastidious
      organisms, including anaerobes. Among the Enterobacteriaceae, > 95% inhibition
      was shared only by imipenem (99.1% at < or = 4 micrograms/ml), and some newer
      cephalosporins (95.1% - 99.8% at < or = 8 micrograms/ml), and piperacillin
      tazobactam (95.8% at < or = 16/4 micrograms/ml). Piperacillin-tazobactam was the
      most active agent tested against nonenteric Gram-negative bacilli (93.5% at < or
      = 8 micrograms/ml). Ampicillin-sulbactam was the most active agent against
      staphylococci (95.0% at < or = 8 micrograms/ml), followed by imipenem (91.8%),
      piperacillin-tazobactam (89.3% at < or = 8/4 micrograms/ml), and cefepime (86.2%
      at < or = 8 micrograms/ml). Against the enterococci, only ampicillin (93.0% at <
      or = 8 micrograms/ml) with or without sulbactam, piperacillin (91.0% at < or = 16
      micrograms/ml) with or without tazobactam, and imipenem (91.0%) had acceptable
      activity. Piperacillin-tazobactam and imipenem were the most active drugs tested
      against all aerobic isolates, inhibiting 93.5% of isolates each. Piperacillin
      tazobactam inhibited all fastidious isolates tested, including Haemophilus
      influenzae (MIC90, 0.094/4 micrograms/ml), Moraxella catarrhalis (MIC90, 0.064/4
      micrograms/ml), Neisseira gonorrhoeae (MIC90, < or = 0.016/4 micrograms/ml), and
      Streptococcus pneumoniae (all MICs, < or = 4/4 micrograms/ml). Against the
      anaerobic isolates, the most broad-spectrum antimicrobial agents tested were
      imipenem (100.0%), piperacillin-tazobactam (99.5% at < or = 32/4 micrograms/ml),
      metronidazole (98.4% at < or = 8 micrograms/ml), and ticarcillin-clavulanic acid
      (95.1% at < or = 32/2 micrograms/ml). These results are nearly identical to a
      previous study involving the same five medical centers in 1989. Piperacillin
      tazobactam appears to remain a highly effective beta-lactamase inhibitor
      combination with a wide empiric spectrum and potency in teaching hospitals.

PMID- 7648837
TI  - In vitro activity of RP 59500 (quinupristin/dalfopristin) against antibiotic
      resistant strains of Streptococcus pneumoniae and enterococci.
AB  - The activity of RP 59500 (quinupristin/dalfopristin) was evaluated in vitro
      against antibiotic-resistant strains of Streptococcus pneumoniae (N = 15) and
      Enterococcus spp. (N = 43). By broth dilution MIC tests RP 59500 was highly
      active against penicillin-resistant S. pneumoniae and vancomycin-resistant
      Enterococcus faecium, but showed poor activity against E. faecalis. In time-kill
      studies the drug was rapidly bactericidal against S. pneumoniae but failed to
      kill most enterococci, even in the presence of gentamicin or human serum.

PMID- 7648838
TI  - Tentative criteria for determining the in vitro susceptibilities of Haemophilus
      influenzae, including quality control parameters, to two fluoroquinolones
      (grepafloxacin and PD 131628).
AB  - Grepafloxacin (OPC 17116) and PD 131628 were evaluated against 150 Haemophilus
      influenzae isolates to propose susceptibility testing criteria for both broth
      dilution and disk diffusion procedures using haemophilus test medium.
      Grepafloxacin-susceptible isolates are defined as those for which minimum
      inhibitory concentrations (MICs) are < or = 0.06 micrograms/ml and zones of
      inhibition are > or = 27 mm. PD 131628-susceptible strains of H. influenzae
      included those that exhibited MICs < or = 0.03 micrograms/ml, and the zones were
      > or = 32 mm. All MICs were well below concentrations that can be achieved in the
      blood and tissues of patients treated with either study drug. Criteria for
      defining a resistant category cannot be determined until strains with elevated
      MICs are available for study. The proposed quality control guidelines for H.
      influenzae ATCC 49247 and the disk test are 32-39 mm in diameter for
      grepafloxacin and 34-42 mm for PD 131628. The preliminary broth microdilution MIC
      control limits for this strain are 0.002-0.016 micrograms/ml for grepafloxacin
      and 0.002-0.008 micrograms/ml for PD 131628.

PMID- 7648839
TI  - Research in psychopathology: epistemologic issues.
AB  - Etiologic research in psychiatry relies on an objectivist epistemology positing
      that human cognition is specified by the "reality" of the outer world, which
      consists of a totality of mind-independent objects. Truth is considered as some
      sort of correspondence relation between words and external objects, and mind as a
      mirror of nature. In our view, this epistemology considerably impedes etiologic
      research. Objectivist epistemology has been recently confronting a growing
      critique from diverse scientific fields. Alternative models in neurosciences
      (neuronal selection), artificial intelligence (connectionism), and developmental
      psychology (developmental biodynamics) converge in viewing living organisms as
      self-organizing systems. In this perspective, the organism is not specified by
      the outer world, but enacts its environment by selecting relevant domains of
      significance that constitute its world. The distinction between mind and body or
      organism and environment is a matter of observational perspective. These models
      from empirical sciences are compatible with fundamental tenets of philosophical
      phenomenology and hermeneutics. They imply consequences for research in
      psychopathology: symptoms cannot be viewed as disconnected manifestations of
      discrete localized brain dysfunctions. Psychopathology should therefore focus on
      how the person's self-coherence is maintained and on the understanding and
      empirical investigation of the systemic laws that govern neurodevelopment and the
      organization of human cognition.

PMID- 7648840
TI  - Communication disturbances in schizophrenia: a two-process formulation.
AB  - We hypothesized that communication disturbances in the form of unclear linguistic
      references in schizophrenia are associated with excess-related pathophysiologic
      processes in some individuals and deficit-related processes in others. We divided
      a sample of 28 acutely ill schizophrenic inpatients into two groups: those with
      negative symptoms and those without. We analyzed audiotaped speech samples from
      each subject, and found that the two groups did not differ significantly on
      overall level of communication disturbance. In patients without negative
      symptoms, level of communication disturbance was associated with severity of
      positive symptoms (r = .62, P < .02) and with neuroleptic responsiveness (r =
      .52, P < .06 [trend]). In those with negative symptoms, level of communication
      disturbance did not correlate with severity of positive symptoms (r = .09, NS),
      and correlated negatively with medication responsiveness (r = -.66, P < .01).
      These findings support a two-process hypothesis of schizophrenic communication
      disturbance.

PMID- 7648841
TI  - Differences and similarities in mixed and pure mania.
AB  - The aim of this study was to examine the relationship between mixed and pure
      mania using both narrow (DSM-III-R) and broad (Cincinnati) operational diagnostic
      criteria to define mixed mania regarding the degree of associated depression.
      Hospitalized patients aged > or = 12 years and meeting DSM-III-R criteria for
      bipolar disorder, manic or mixed, were compared regarding demographics,
      phenomenology, course of illness, comorbidity, family history, and short-term
      outcome. Seventy-one patients were recruited during a 1-year period. Twenty-four
      patients (34%) met DSM-III-R criteria for mixed bipolar disorder; 28 (40%) met
      the broader definition (which required three associated depressive symptoms
      rather than full syndromal DSM-III-R depression). Compared with pure manic
      patients, DSM-III-R mixed patients had significantly more depressive symptoms,
      were more likely to be female, experienced more prior mixed episodes, displayed
      higher rates of comorbid obsessive-compulsive disorder, and had longer
      hospitalizations. However, when mixed mania was defined more broadly, differences
      in gender and hospitalization length were lost. Also, regardless of the
      definition used, mixed and pure manic patients were similar on most other
      variables assessed. We conclude that mixed and pure mania differ in some respects
      but have many similarities, especially when mixed mania is defined by lesser
      degrees of depression. The use of dimensional rather than categoric systems to
      describe the degree of associated depression may be a more meaningful method of
      classifying mania.

PMID- 7648842
TI  - Alexithymia in panic disorder and social phobia.
AB  - Two recent studies have found that small samples of panic disorder patients
      appear to have elevated levels of alexithymia and raised the possibility that
      panic patients may constrict emotional experience. An alternate hypothesis is
      that there is conceptual and measurement overlap between alexithymia and
      cognitive aspects of panic disorder, and panic patients may in fact score high on
      only one dimension of alexithymia. One hundred panic disorder patients and 46
      social phobics completed the revised 20-item Toronto Alexithymia Scale (TAS) and
      several anxiety-related measures. Thirty-four percent of panic patients and 28.3%
      of social phobics were classified as alexithymics, a nonsignificant difference.
      However, the alexithymia dimension related to difficulties in identifying and
      differentiating emotions and physical sensations was significantly elevated as
      compared with the alexithymia dimension related to external-oriented thinking.
      The former dimension was also significantly correlated with anxiety measures. The
      apparent finding that a sizeable proportion of panic patients are alexithymic may
      be an artifact of conceptual and psychometric overlap with cognitive aspects of
      panic disorder, specifically the interoceptive focus and sensitivity often
      associated with panic attacks.

PMID- 7648843
TI  - Who participates in a family study?
AB  - Potential subject participation biases in a family study of outpatients with mood
      disorders and personality disorders (PDs) were explored at three levels: (1)
      differences between probands who granted permission to contact all relatives,
      those who gave permission to contact only a subset of relatives, and those who
      denied permission to contact any relatives; (2) differences between relatives
      whom the proband granted permission to contact and those whom the proband denied
      permission to contact; and (3) for the relatives who could be contacted,
      differences between those who agreed to participate and those who declined.
      Subjects included 156 outpatients with mood disorders and PDs and 611 of their
      first-degree relatives. Axis I and II disorders in probands and relatives were
      evaluated using structured diagnostic interviews. In addition, informant reports
      on relatives were obtained from family history (FH) interviews. Results indicated
      that probands who gave and who withheld consent to contact their relatives did
      not differ significantly on most variables. However, relatives whom we were not
      permitted to contact were significantly more likely to have drug abuse and PDs.
      Finally, of the relatives we were permitted to contact, there were few
      differences between those who participated in the study and those who refused to
      participate. These findings indicate that the greatest risk of sampling bias in
      family studies stems from probands' reluctance to grant access to relatives with
      drug abuse and PDs.

PMID- 7648844
TI  - Stressors and close relationships during childhood and dissociative experiences
      in survivors of sexual abuse among inpatient psychiatric women.
AB  - The purpose of this study was to examine which childhood events were associated
      with more extensive use of adult dissociative states in 90 female inpatients with
      histories of sexual abuse. The study found that childhood stressors of
      maltreatment (physical neglect, witnessing sexual abuse, and witnessing physical
      abuse) were associated with higher levels of dissociative symptoms. In contrast,
      childhood stressors of loss (parental separation and death of a close relative)
      were not related to increased severity of dissociative symptoms. The study also
      demonstrated that a close relationship with either a parent, sibling,
      extraparental adult, or friend did not have a mediating effect on the degree of
      adult dissociative symptoms. Directions for future research are presented.

PMID- 7648845
TI  - Cognitive impairment in psychiatric patients and length of hospital stay.
AB  - The purpose of this study was to determine whether brief neuropsychologic
      screening at the time of admission to an acute-care psychiatric unit predicts the
      length of inpatient hospital stay (LOS). Over a 4-month period, 41 consecutively
      admitted patients on a general psychiatric inpatient unit were administered the
      Mini-Mental State Examination (MMSE), the Trails A and B subtests from the
      Halstead-Reitan Neuropsychological Battery, and the Visual Reproduction subtest
      (VR) of the Wechsler Memory Scale within 72 hours of admission. A setwise,
      hierarchic multiple regression model examined the contributions of demographic
      factors, clinical features, and the four neuropsychologic tests to LOS variance.
      VR and Trails A were the best predictors of LOS, responsible for 21.6% and 16.3%
      of outcome variance, respectively. The independent variables (IVs) comprising the
      best-fitting model include Trails A, VR, MMSE, and patient diagnosis. These
      variables collectively accounted for 48.8% of the variance in LOS, and predicted
      70.4% of patients with LOS < 21 days and 82.4% of patients with LOS > 21 days.
      The results of this study support the hypothesis that LOS is related to cognitive
      impairment associated with psychiatric illness, and suggest that neuropsychologic
      testing upon admission to an inpatient unit can be useful in predicting LOS.

PMID- 7648846
TI  - Cotard's delusion or syndrome?: a conceptual history.
AB  - This report offers an account of the historical construction of Cotard's syndrome
      showing that by delire des negations the French author meant a subtype of
      depressive illness. Subsequent debate led first to the belief that it was just a
      collection of symptoms associated with agitated depression (anxious melancholia)
      or general paralysis, and later to the view that it might after all constitute a
      separate entity. At the present moment, and impervious to the fact that the
      French term delire means far more than "delusion," some authors use Cotard's
      syndrome to refer to the belief of being dead and suggest that such a delusion
      might have a specific brain location. From the clinical and evolutionary
      perspective, it is unclear why a delusion should merit, simply because of its
      "nihilistic" content, a special brain location or presage chronicity. It is
      suggested here that before neurobiologic speculation starts, efforts should be
      made to map out the clinical features and correlations of the delire des
      negations.

PMID- 7648847
TI  - Psychiatric morbidity in travelers to Honolulu, Hawaii.
AB  - To investigate the phenomenon of acute psychiatric decompensation in travelers,
      charts of all psychiatric-emergency patients with a history of recent travel
      involving time-zone changes were reviewed at a major medical center in Honolulu,
      HI. Charts of a control group with no history of travel were also reviewed.
      Significantly more travelers than controls showed symptoms of depression and
      mania (P < .012). East-bound travelers were significantly more likely to show
      symptoms of mania than controls (P < .001). In an eastbound-versus-westbound
      comparison, significantly more eastbound travelers showed symptoms of mania,
      whereas significantly more westbound travelers showed symptoms of depression (P <
      .05). These findings support the phase-advance hypothesis of depression.
      Psychosocial and biologic factors that may contribute to psychiatric
      decompensation in travelers are discussed.

PMID- 7648848
TI  - Suicidal behavior and abuse in psychiatric outpatients.
AB  - The present study examines the relationship between suicidal behaviors and
      histories of abuse in psychiatric outpatients. Two hundred fifty-one psychiatric
      outpatients were evaluated for history of abuse, suicidal behavior, demographics,
      and clinical characteristics using self-report instruments and a face-to-face
      interview. Logistic regression analysis indicated that physical abuse (battering)
      in adulthood and histories of a combination of childhood and adulthood abuse were
      significant predictors of past suicide attempts and current suicidal ideation.
      Victims of abuse were more likely than nonvictim controls to have been suicidal
      at a younger age and to have made multiple suicide attempts. Among patients with
      a history of abuse, suicide attempters could be distinguished from nonattempters
      on the basis of higher levels of dissociation, depression, and somatization.
      Abusive experiences in adulthood appear to play an important role in suicidal
      behavior among psychiatric outpatients. High levels of specific symptoms (i.e.,
      depression, somatization, and dissociation) among patients with a history of
      abuse can help to identify outpatients at risk for suicidal behavior.

PMID- 7648849
TI  - Hyperphosphatemia: an objective marker for bulimia nervosa?
AB  - Phosphorus abnormalities among patients suffering from eating disorders, although
      cited, have received relatively little attention. Studies generally report
      decreased concentrations of phosphorus for both bulimia and anorexia nervosa. We
      have recently noted hyperphosphatemia in several consecutive hospitalized bulimic
      patients who appeared to have normal renal function and calcium levels. Case
      files of 30 inpatient and outpatient female bulimic patients and 30 sex- and age
      matched physically healthy psychiatric inpatients and outpatients were reviewed.
      Phosphorus and electrolytes related to phosphorus metabolism were compared
      between the two groups. Twenty-four of 30 bulimic patients (80%) were found to
      have at least one elevated serum phosphorus concentration, whereas all but one of
      30 age-matched controls had values within normal limits. Elevated phosphorus
      levels were generally in the mild to moderate range. No correlation was found
      between phosphorus levels and any of the other electrolytes examined in both
      patients and controls. No correlation was found between phosphorus levels and the
      reported frequency of bingeing and vomiting or the number of laxatives ingested.
      Since bulimic patients are generally of normal weight and tend to deny their
      disturbed eating habits, diagnosis is often delayed. However, bulimia may be
      suspected from biochemical abnormalities such as hypokalemia, hypochloremia,
      elevated amylase, and acid-base disturbances. This preliminary study indicates
      that elevated serum phosphorus levels may serve as an additional objective marker
      for the presence of bulimia nervosa.

PMID- 7648850
TI  - Surveillance of cancer incidence in Connecticut counties and towns, 1989-91.
AB  - Using the population-based Connecticut Tumor Registry, cancer incidence was
      examined for residents of Connecticut's eight counties and 169 towns in 1989-91.
      Findings included high standardized incidence ratios (SIRs) for: certain smoking
      related cancers for women in New London County; several cancers (bladder, kidney,
      and mesotheliomas) for men in Middlesex County; Kaposi's sarcoma in Fairfield
      County, and in the towns of Hartford and New Haven; skin melanoma in certain
      ocean-shoreline towns; and invasive cervical cancer in several larger cities.
      Cancer surveillance data should be useful for promoting such efforts as smoking
      prevention and cessation, the collection of data on occupation and smoking by
      physicians and hospitals, reduction in excessive sun exposure, and increased
      screening for cervical cancer in large towns.

PMID- 7648851
TI  - Bladder stones formation eight months after treatment of hairy-cell leukemia with
      2-chloro-deoxyadenosine: a case report.

PMID- 7648852
TI  - The use of zidovudine to prevent perinatal transmission of HIV.

PMID- 7648853
TI  - Physicians' retirement.
AB  - There are few guidelines available for physicians approaching retirement. Since
      many physicians do not enjoy their years after practice, guidelines for making
      this time of life enriching and a period of intellectual growth can be helpful.

PMID- 7648854
TI  - The new president's message.

PMID- 7648855
TI  - Why not limit Medicare growth?

PMID- 7648856
TI  - Regarding the credibility of childhood memories of sexual abuse.

PMID- 7648857
TI  - Declining services for the chemically dependent.

PMID- 7648858
TI  - In vitro model for corneal wound healing; organ-cultured human corneas.
AB  - Healing of linear, non-perforating thermal burns was studied in 56 human corneas
      in an air/liquid organ culture system in serum free medium or in media
      supplemented with 10% fetal bovine serum, 10% human serum or 10% human plasma.
      The extent of epithelial wound healing was determined by measuring epithelial
      growth into the wound using digitized computer scanning of light micrographs of 1
      micron sections. The cross-sectional area of this epithelial growth entering the
      wound was significantly greater for corneas incubated with either human serum
      (16,350 +/- 12,088 microns 2/day; p < 0.0001) or human plasma (20,571 +/- 12,276
      microns 2/day; p = 0.0004) than for those incubated in serum free (1,784 +/-
      1,957 microns 2/day) medium. There was no significant difference between
      epithelial growth in the serum free and fetal bovine serum supplemented (3,779 +/
      2,580 microns 2/day) media or between that in human serum and human plasma
      supplemented media. The thickness of the epithelium adjacent to the wound was
      greater in corneas cultured in fetal bovine serum supplemented media than in
      corneas cultured in the presence of human serum. Similarly, the build-up of
      epithelium at the wound edge for corneas in either serum free or fetal bovine
      serum supplemented media was significantly greater than for either human serum or
      human plasma supplemented media. The percentage of basal epithelial nuclei which
      incorporated bromodeoxyuridine (BrdU) increased during the first three days of
      culture when it reached a plateau. Comparison of paired wounded and unwounded
      corneas showed that wounding stimulated an increase in DNA synthesis.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7648859
TI  - Release of platelet activating factor (PAF) and eicosanoids in UVC-irradiated
      corneal stromal cells.
AB  - Ultraviolet (UV) irradiation provokes acute inflammation of the eye, and can be
      used to model processes that occur in response to damage to the anterior segment.
      This study characterized ultraviolet-C (UVC, 254 nm) irradiation-induced PAF
      synthesis, and arachidonic acid (20:4) and eicosanoid release in rabbit corneal
      stromal cells maintained in vitro. PAF was measured by radioimmunoassay (RIA)
      after exposing cultured corneal stromal cells to UVC irradiation (20 min, 2, 5,
      10 mW/cm2). 14C-20:4-labeled stromal cells were also stimulated with UVC and
      radiolabeled phospholipids, neutral lipids and eicosanoids were measured.
      Synthesis of cell-associated and secreted PAF from corneal stromal cells was
      increased by UV irradiation. UV irradiation (254 nm, 5mW/cm2) enhanced 20:4
      release from triacylglycerols, phosphatidylinositol, phosphatidylserine and
      phosphatidylethanolamine, and increased levels of 20:4-diacylglycerol and
      unesterified 20:4. The released 20:4 entered both the cyclooxygenase and
      lipoxygenase pathways after UVC irradiation. The PAF antagonist, BN52021 (10
      microM) reduced UVC irradiation-induced stimulation of prostaglandin production,
      but failed to inhibit UVC-induced 20:4 release and synthesis of lipoxygenase
      products. Furthermore, exogenous PAF (1 microM) stimulated prostaglandin
      production, but did not increase the synthesis of lipoxygenase products from
      radiolabeled 20:4. The effects of PAF on prostaglandin synthesis were inhibited
      by BN52021. These findings indicate that responses to injury in cultured corneal
      stromal cells include PAF synthesis, release of 20:4 from glycerolipids,
      accumulation of diacylglycerol and synthesis of eicosanoids. The data further
      suggest that during UVC irradiation in vitro, PAF is not a primary or initial
      mediator of 20:4 release and synthesis of lipoxygenase products, but may mediate
      UVC-induced prostaglandin synthesis.

PMID- 7648860
TI  - The association between pH level and corneal recovery from induced edema.
AB  - Corneal acidosis has been shown to reduce corneal hydration control (CHC) as
      measured by the rate, expressed as the percent recovery per hour (PRPH), at which
      the thickness of the cornea decreases exponentially after an increased hydration
      load. Since the effect of pH on corneal function is of scientific interest and
      may have clinical implications, we explored the relationship between pH and PRPH
      in greater detail by examining the effect of different stromal pH levels on
      corneal hydration control. Corneal edema was induced using a 90-min exposure to
      wearing a hypoxic contact lens (CL). Following removal of the CL, random
      assignment over four eye-test combinations of either 0, 3, 5, and 7% CO2 were
      made while pH and corneal thickness were monitored using slit lamp fluorophometry
      and optical pachometry to measure corneal pH and corneal thickness, respectively.
      From these measurements we determined the pH-dose/PRPH relationship. The average
      stromal pH +/- 1SD resulting from exposure to either the 0, 3, 5, and 7% CO2, was
      7.65 +/- 0.11, 7.30 +/- 0.09, 7.15 +/- 0.08 and 7.04 +/- 0.07 (p < 0.001),
      respectively. Analysis based on a quadratic model of the dose-response
      relationship between PRPH and corneal pH indicates that PRPH is relatively
      unchanged for pH in the physiological range (pH = 7.40-7.65) and then decreases
      notably below the physiological range.

PMID- 7648861
TI  - A non-enzymatic method for lens decapsulation which leaves the epithelial cells
      attached to the fibers.
AB  - We have developed a method to mechanically decapsulate the lens yet leave the
      epithelial cells attached to the fibers. This method uses divalent ion chelaters
      to loosen the capsule-epithelial interactions and bumetanide to control cell
      swelling. Light microscopy, scanning electron microscopy, and in-vitro
      fluorescence microscopy demonstrate that the capsule is removed and the
      epithelial cells remain adherent to the fibers when these procedures are used.
      Ion channel activity and epithelial gap junction communication remain following
      decapsulation. This decapsulated lens preparation should prove useful for many
      kinds of lens studies.

PMID- 7648862
TI  - Tear lipocalins bind a broad array of lipid ligands.
AB  - To identify the native ligands of tear lipocalins, tear proteins were separated
      by size exclusion chromatography and the lipid content in the major protein
      fractions identified. Lipids extracted from native tears and purified tear
      lipocalins comigrated with fatty acids, fatty alcohols, phospholipids,
      glycolipids, and cholesterol on thin layer chromatograms. Abundant stearic and
      palmitic acids as well as cholesterol, and lesser amounts of lauric acid were
      specifically identified in extracts of purified lipocalins by gas chromatography
      mass spectroscopy. A preliminary study of the ligand-protein interaction was
      carried out using nitroxide spin-labeled lipids.

PMID- 7648863
TI  - Effects of pharmacological modulation of intracellular signalling systems on
      retinal pigment epithelial cell attachment to extracellular matrix proteins.
AB  - Complication of retinal detachment by proliferative vitreoretinopathy (PVR) is
      common. In the contraction of intraocular collagen matrices which occurs in PVR
      cell proliferation, migration and adhesion seem to be more important than any
      inherent cellular contractility. The aim of this study was to investigate the
      pharmacological inhibition of adhesion of retinal pigment epithelial cells to
      extracellular matrices. The adherence of human RPE lines to a range of ten
      substrates was assessed to determine their preferred substrates for attachment.
      The effect of pharmacological inhibitors and stimulators of protein kinase C,
      cyclic AMP and calcium/calmodulin intracellular signal transduction systems on
      attachment to substrates was investigated. RPE cells showed a clear substrate
      preference for fibronectin, and slight preference for collagen type I. Modulation
      of the protein kinase C and cAMP pathways had relatively minor effects upon RPE
      attachment. Increasing intracellular calcium concentration reduced RPE attachment
      to 12% of control, whilst reducing intracellular calcium had a less marked,
      although significant effect. Down-regulation of calmodulin reduced attachment to
      17% of control. The drug tamoxifen, and the experimental calmodulin antagonist
      J8, produced significant inhibition of attachment even when cells had been
      allowed to adhere for 24 h prior to exposure to these agents. The adhesion of RPE
      to extracellular matrices may be markedly affected by drugs which modulate the
      intracellular calcium and calmodulin signalling systems. Calmodulin antagonists
      warrant further investigation as possible pharmacological inhibitors of PVR.

PMID- 7648864
TI  - Retinal dopamine and lens-induced refractive errors in chicks.
AB  - This study investigated the relationship between retinal dopamine and lens
      induced refractive errors in chicks by high performance liquid chromatography
      with ultraviolet detection (HPLC-UV). After two weeks of lens wear, the chick
      eyes treated with +10D lenses were hyperopic (+8.29 +/- 0.43D), while the eyes
      treated with -10D lenses were myopic (-11.69 +/- 0.74D). At the same time, in
      myopic eyes the level of retinal dopamine and its metabolite 3,4-dihydroxy
      phenylacetic acid (DOPAC) were reduced compared to control eyes, while in
      hyperopic eyes the level of retinal dopamine and DOPAC were increased as compared
      with control eyes. Therefore, retinal dopamine may participate in the development
      of lens induced refractive errors in chicks.

PMID- 7648865
TI  - Atrial natriuretic peptide stimulates Cl- transport in retinal pigment epithelial
      cells.
AB  - To study the regulatory role of atrial natriuretic peptide (ANP) on the Cl-
      transport activity of retinal pigment epithelial (RPE) cells, RPE cells from
      rabbits were cultured and exposed to ANP and other reagents under perfusion. The
      changes in intracellular Cl- concentration ([Cl-]i) were continuously recorded
      using a Cl(-)-sensitive fluorescent dye. The cGMP content was estimated by
      radioimmunoassay. ANP increased the cGMP content and the [Cl-]i in RPE cells. A
      guanylate cyclase activator, nitric oxide, and a cell permeable cGMP precursor, 8
      Br-cGMP, also increased the level of cGMP and the [Cl-]i. A guanylate cyclase
      inhibitor, LY83583, an inhibitor of cGMP-dependent protein kinase, KT5823, and an
      inhibitor of Na+/K+/2Cl- cotransporter, bumetanide, diminished or abolished the
      ANP-induced increase in [Cl-]i. ANP facilitates Cl- accumulation in RPE cells,
      which is mediated by guanylate cyclase, cGMP-dependent protein kinase, and the
      Na+/K+/2Cl- cotransporter.

PMID- 7648866
TI  - Murine model of anterior and posterior ocular melanoma.
AB  - Iris melanomas are less likely to metastasize than ciliary body or choroidal
      melanomas. In order to study this difference in metastatic rate, we developed a
      murine model of anterior chamber (AC) and posterior compartment (PC) melanoma.
      Eighteen C57BL6 mice were inoculated in the AC (n = 6) or PC (n = 12) with B16F10
      melanoma cells and eleven mice were inoculated in the AC (n = 3) or PC (n = 8)
      with Queens melanoma cells. The animals were sacrificed at 12 to 14 days post
      inoculation and histologically examined. Results were that 8 of 9 AC tumors and
      10 of 20 PC tumors grew. One PC tumor metastasized to the lungs. This model may
      be used to study anterior versus posterior ocular melanoma differences.

PMID- 7648867
TI  - Effects of surgical sympathetic denervation on G-protein levels, alpha and beta
      adrenergic receptors, cAMP production and adenylate cyclase activity in the
      smooth muscles of rabbit iris.
AB  - The relative densities of a number of G protein subunits were quantified in
      membranes prepared from iris sphincter and dilator muscles of rabbits that have
      undergone sympathetic denervation and from contralateral innervated controls by
      immunoblotting with specific polyclonal antibodies against Gs alpha, Gi alpha and
      Gq alpha protein subunits. In addition, alpha and beta-adrenergic receptor
      densities, basal and isoproterenol (ISO)-stimulated cAMP production, and basal
      and ISO+GTP gamma S-stimulated adenylate cyclase (AC) activities were measured in
      the same tissues. Densitometric analysis of the immunoblot data revealed a 32%
      reduction in the level of Gi alpha in the denervated sphincter, a 26% increase in
      the level of Gi alpha in the denervated dilator, and no changes due to
      denervation were found in the levels of Gs alpha and Gq alpha. Sympathetic
      denervation had no effect on the densities of alpha- and beta-adrenergic
      receptors in these tissues, however, it did induce a significant decrease in the
      KD values of alpha-adrenergic receptors in both dilator and sphincter, and in
      beta-adrenergic receptors in the sphincter. The basal- and ISO-stimulated cAMP
      production in the sphincter was 4-fold as high as that of the dilator, and at
      0.05 microM ISO the denervation supersensitivity for cAMP production in the
      sphincter increased by 118% as compared to 36% in the dilator. Sympathetic
      denervation increased by 19-47% the basal- and ISO-stimulated activity of AC in
      these tissues, however, it had no effect on the phospholipase C
      activity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7648868
TI  - Galactosylation of rhodopsin by the human retina.
AB  - The major oligosaccharide chains of bovine, frog and human rhodopsins are
      abridged, hybrid, asparagine-linked structures that contain only mannose and N
      acetylglucosamine as the constituent sugars. Isomers that also contain galactose
      have been detected in varying amounts in rhodopsins from different species. As
      part of studies to examine the mechanisms used by the human retina to control the
      glycosylation of rhodopsin, the kinetics of the retinal galactosyltransferase was
      examined using Golgi-enriched fractions of human retina as the enzyme source and
      rhodopsin, opsin, and the oligosaccharide isolated from rhodopsin as acceptors.
      These reactions were compared to those using bovine retina and rat liver Golgi. A
      comparison of the Vmax/Km ratios revealed that the efficiency of the human
      retinal galactosyltransferase was some 20-fold lower than that of the rat liver.
      In addition, consistent with the higher state of galactosylation of human as
      compared to bovine rhodopsin, greater efficiency was observed with the human
      preparation. While the conformation of the visual pigment exerted an effect, its
      low galactosylation was not due to a major directing influence on glycosylation
      by the polypeptide matrix as indicated by the even lower activity toward the
      isolated oligosaccharide. The galactosylated oligosaccharides obtained by these
      procedures were identified by chromatographic methods. The relatively low
      activity of the retinal galactosyltransferases observed in this study may help
      explain the limited glycosylation that is typical of rhodopsin.

PMID- 7648869
TI  - The role of systemic cyclosporine dosing schedule on corneal allograft survival
      in the rat model.
AB  - We evaluated the role of preoperative versus postoperative systemic Cyclosporin A
      (CsA) on corneal allograft survival in the rat model. All treatment regimens were
      administered by daily intramuscular injection until rejection. In the
      preoperative group (n = 9), CsA (7.5 mg/kg/day) was started ten days
      preoperatively. In the postoperative group (n = 9), CsA (7.5 mg/kg/day) was
      started immediately postoperatively. In the injectable control group (n = 7),
      injections of 0.9% normal saline with olive oil began the day of surgery. A
      masked observer performed alternate day slit lamp evaluations of graft opacity,
      edema, and vascularity. The median rejection times [days (range)] for the
      injection control, preoperative and postoperative groups were: 11 (10-17), 17 (12
      53), and 28 (12-53), respectively. The grafts in the postoperative and
      preoperative treatment groups survived longer than the control (p = 0.003 and p =
      0.005 respectively). There was no statistical difference between the preoperative
      and postoperative groups (p = 0.3). Preoperative systemic administration of CsA
      may offer no significant benefit in prolonging allograft survival over treatment
      beginning the day of surgery.

PMID- 7648870
TI  - Regulation of foamy virus gene expression.

PMID- 7648871
TI  - The human immunodeficiency virus type 1 Vpu protein: roles in virus release and
      CD4 downregulation.

PMID- 7648872
TI  - Viral protein X.

PMID- 7648873
TI  - The pathogenic role of human immunodeficiency virus accessory genes in transgenic
      mice.

PMID- 7648874
TI  - The human immunodeficiency virus type 1 vif gene: the road from an accessory to
      an essential role in human immunodeficiency virus type 1 replication.

PMID- 7648875
TI  - Nef.

PMID- 7648876
TI  - The vpr regulatory gene of HIV.

PMID- 7648877
TI  - Transactivation of cellular genes by human retroviruses.
AB  - We have focused this chapter on interactions with two of the best characterized
      transregulatory genes, tax for HTLV-I/II and Tat for HIV-1. Both genes illustrate
      the complex interplay between retroviral regulatory genes and cellular gene
      regulation. In both instances a viral gene of relatively straightforward function
      in the viral context appears to cause extensive dysregulation of cellular genes,
      either directly or as a consequence of altered cellular differentiation.
      Understanding this viral/cellular gene cross-talk may elucidate mechanisms
      leading to malignant transformation autoimmune disease and to neurologic and
      paraneoplastic complications such as hypercalcemia for HTLV-I/II, as well as the
      pathogenesis of immune dysfunction and opportunistic malignancy in HIV-I/II
      infected individuals. An understanding of functional mechanisms of these
      transregulatory viral genes will undoubtedly afford better explanations for the
      myriad manifestations of retroviral infection.

PMID- 7648878
TI  - Regulation of HIV-1 gene expression by the transactivator protein Tat.

PMID- 7648879
TI  - HTLV-1 oncoprotein tax and cellular transcription factors.

PMID- 7648881
TI  - The most powerful medicine.

PMID- 7648880
TI  - The human immunodeficiency virus type 1 Rev protein: a pivotal protein in the
      viral life cycle.

PMID- 7648882
TI  - Systemic contact dermatitis due to intravenous Valium in a person sensitive to
      propylene glycol.

PMID- 7648883
TI  - A dermatologic diary. Portrait of a practice.

PMID- 7648884
TI  - Childhood acanthosis nigricans.

PMID- 7648885
TI  - Sarcoidosis: nail dystrophy without underlying bone changes.
AB  - Sarcoidosis is a chronic granulomatous disease of unknown origin that affects
      multiple organs and may present with a variety of skin lesions. Involvement of
      the nails is rare and almost invariably associated with underlying bone disease.
      We describe a patient with sarcoid nail dystrophy in whom this diagnosis was
      confirmed by a proximal nail fold biopsy. Radiologic investigation did not show
      evidence of an associated bone dystrophy in this case.

PMID- 7648886
TI  - Helical hairs: a new hair anomaly in a patient with Netherton's syndrome.
AB  - A new hair shaft defect, helical hair, is presented. This hair abnormality was
      found to accompany trichorrhexis invaginata and pili torti in an infant with
      Netherton's syndrome. The patient's main clinical features included erythroderma
      since birth, failure to thrive, recurrent infections, hepatosplenomegaly,
      lymphadenopathy, eosinophilia, hypergammaglobulinemia, and high serum IgE levels.
      A possible mechanism for the formation of helical hair is reviewed.

PMID- 7648887
TI  - Dermatologic stigmata in sports: water skiing.
AB  - Every athletic endeavor results in dermatologic stigmata specific to it. We
      illustrate here such a stigmata associated with water skiing.

PMID- 7648888
TI  - Dermatitis artefacta revisited.
AB  - Self-induced factitial dermatitis, or dermatitis artefacta, is a rare and
      difficult condition to treat. We present an unusual case of factitious dermatitis
      with its subsequent severe complications. The clinical features, radiographic
      findings, histopathologic features, and treatment options are reviewed.

PMID- 7648889
TI  - Inflammatory linear verrucous epidermal nevus in patients with positive results
      of tests for human immunodeficiency virus 1.
AB  - Inflammatory linear verrucous epidermal nevi are rare lesions that have many
      similarities to psoriasis on histologic examination, and are resistant to
      therapy. The two lesions reported occurred in patients with positive results of
      tests for human immunodeficiency virus 1 and showed features consistent with
      psoriasis. Results of tests for immunohistochemical markers were also consistent
      with previous findings and expected staining patterns in lesions of psoriasis.
      Our findings suggest that inflammatory linear verrucous epidermal nevi represent
      a clonal dysregulation in growth, probably secondary to an inflammatory stimulus.
      Since human immunodeficiency virus 1 has been associated with onset and
      exacerbation of psoriasis, perhaps this virus or another secondary infection
      associated with human immunodeficiency virus 1 infection could also play a role
      in the onset of this rare lesion.

PMID- 7648890
TI  - Scabies: the diagnosis of atypical cases.
AB  - In the current scabies pandemic, classic scabies is seen less frequently and
      special forms are becoming more common. The diagnosis of scabies has become,
      therefore, a challenge for clinicians. The well-known scabietic burrow is seen
      only very rarely today and, therefore, pathognomonic as it is, the diagnosis of
      scabies should not rely on this clinical sign. In our experience, examination of
      skin scrapings mounted on a slide with saline is the most practical bedside
      method and ideal for screening patients with suspected scabies. It is easy to
      perform, requires neither sophisticated tools nor special skill, and can be done
      in less than five minutes by every practitioner.

PMID- 7648891
TI  - Chest 1995. New York, New York, October 29-November 2, 1995. Abstracts.

PMID- 7648892
TI  - [Renal artery aneurysms. Our experience].
AB  - A retrospective study concerned 8 aneurysms of the renal artery. There were 6
      females and 2 males with a mean age of 50.7 years. Diagnosis was obtained
      angiographically in all cases, in 7 during a reno-vascular work-up for
      hypertension and fortuitously in 1 after angiography for arteriopathy of the
      lower limbs. The aneurysm was due to fibromuscular dysplasia in 5 cases and to
      atheromatous lesions in 3. Reconstruction techniques and their indications were
      analyzed on the basis of a review of the literature. Outcome for hypertensive
      patients are the same for the different techniques.

PMID- 7648893
TI  - [Thrombophlebitis of the ovarian vein in the postpartum period. Diagnostic and
      therapeutic problems].
AB  - Three cases of thrombophlebitis of the ovarian vein occurred early after
      delivery. The thrombus extended into the inferior vena cava in all three cases
      and led to pulmonary emboli in one patient. The clinical presentation was
      suggestive of the diagnosis which was confirmed by echography and computed
      tomography. Heparin and antibiotics were given at diagnosis and thrombectomy of
      the inferior vena cava was performed in 2 cases with a vibrating thrombus.
      Ligature was required in these cases. The clinical case was favourable in all
      three cases.

PMID- 7648894
TI  - [Role of pelvic exenterations in the treatment of cervix cancers. Apropos of 41
      surgically treated cases].
AB  - The Department of surgical oncology of the Paul-Strauss Cancer Center of
      Strasbourg (France) reports its experience about pelvic exenterations in
      recurrent cervix carcinomas. Based on a series of 41 cases (median age: 48.5
      years), all patients, but one, have been primarily treated by sole external beam
      irradiation or surgery combined with radiotherapy. Salvage ultraradical surgical
      procedures were total (25 cases), anterior (7 cases) and posterior exenterations
      (9 cases). Overall 5 and 10 years crude survival were 39 and 27.5%, respectively.
      Advances in surgical procedures, new developments in techniques of pelvic floor
      reconstruction and improvement in devices of urinary diversions have mainly
      contributed to a decrease of postoperative morbidity associated with the
      obtaining of long survivals in selected patients previously treated, in a
      curative intent, by other therapeutic modalities. The current place of palliative
      pelvic exenterations and the support of intraoperative radiotherapy are discussed
      according to recent literature data.

PMID- 7648895
TI  - [Neoplastic grafts after celioscopic biliary surgery].

PMID- 7648896
TI  - [Cancer and laparoscopic surgery in gynecology].

PMID- 7648897
TI  - [Tumor dissemination after celioscopic treatment of an ovarian tumor].

PMID- 7648898
TI  - [Parietal metastases and early local recurrences after celioscopic colonic
      surgery].

PMID- 7648899
TI  - [Video-endoscopic surgery and cancer of the esophagus: reflections].

PMID- 7648900
TI  - [Surgical strategy in the association: aneurysm of the abdominal aorta and
      colonic lesion].
AB  - An association of an aneurysm of the abdominal aorta and a lesion of the colon
      raises an important question as to the correct sequence to follow. A simultaneous
      operation raises the major risk of infection and most authors prefer a sequential
      approach, treating either the aneurysm or the lesion of the colon first depending
      on the initial clinical situation or complications. In our first patient, both
      pathologies were known before surgery and simultaneous procedures were
      deliberately programmed. In the second case, both lesions were complicated and
      required simultaneous cure. In the third case, both were recognized before
      surgery and a sequential approach was followed--colon then abdominal aorta. In
      the fourth case, the colon disease was complicated and responded to medical
      treatment; three months later surgery was performed on the aneurysm followed by a
      colectomy two months later. A review of the literature and an analysis of our
      four cases offer a means of developing a management strategy for patients with an
      aneurysm of the abdominal aorta associated with a lesion of the colon.

PMID- 7648901
TI  - [Surgical treatment of paraesophageal hiatal hernia with total intrathoracic
      volvulus of the stomach].
AB  - From 1971 to 1993, we operated 44 patients, 34 females and 10 males with a
      paraoesophageal hernia in which the entire stomach entered the thorax. Mean age
      of the patients was 70 years. Seventeen patients underwent emergency surgery for
      strangulated hernia leading to complete ghastric occlusion, gastric bleeding or
      necrosis (3 cases). Only 2 patients had a past history of gastro-oesophageal
      reflux. The following techniques were used: abdominal access in all cases,
      saccular resection, closure of the widened hiatus or of a left sided hernial
      hiatus, anterior gastropexy suturing the greater curvature to the abdominal on
      the left. Several patients were in precarious clinical situations and had to be
      treated under local or regional anaesthesia alone. Two patients had partial
      necrosis of the stomach and were treated by partial gastropexy. There were no
      deaths or major complications. Incomplete recurrence was noted in one patient 2
      years after the initial procedure. IN CONCLUSION: 1) abdominal access is much
      preferable; 2) an antireflux procedure is only indicated when the patients have
      signs of gastro-oesophageal reflux; 3) most complications are not due to the
      hernia itself but to gastric volvulus. Consequently, simple reduction of the
      hernia followed by anterior gastroplexy under local anaesthesia can give
      excellent results in patients in precarious clinical situations and argues
      against major operation with general anaesthesia; 4) due to the gravity of
      paraesophageal hernia, a surgical solution is required as soon as diagnosis has
      been confirmed.

PMID- 7648903
TI  - [New challenge of studies on gynecologic oncology].

PMID- 7648902
TI  - [Conservative treatment of hepatic injuries. Management and course].
AB  - From January 1986 to June 1994, 252 cases of closed liver trauma were treated in
      an emergency setting. Non surgical conservative management, after a complete
      imaging work-up including CT scan in all cases, was applied in 142 cases (56.3%)
      with no hemodynamic complication. The spontaneous outcome in these cases was
      quite favourable in 131 (92.2%); all lesions had disappeared in 4 to 36 weeks.
      Complications were observed in only 6 cases: 2 intrahepatic abscesses managed
      with percutaneous drainage were not further complicated, 1 biliari fistula
      required surgical exploration, 1 intrahepatic bilioma was drained percutaneously,
      1 disinsertion of the gallbladder was treated by laparoscopy and 1 operation for
      bleeding was required 48 hours after the trauma in 1 case. No deaths could be
      directly imputed to the liver trauma, 5 patients died from neurological causes.
      Non-surgical conservative treatment combined with strict prolonged surveillance
      is a reliable management option for patients with closed liver trauma.

PMID- 7648904
TI  - [Clinical evaluation of the vulva reconstruction with myocutaneous flap
      transposition after radical vulvectomy].
AB  - Thirty-three cases with carcinoma of vulva were treated in the division of
      gynecologic oncology from July, 1989 to April, 1994. Out of 33 cases, 18 with
      stage II or III underwent radical vulvectomy, pelvic and inguinal
      lymphadenectomy. These were divided into 3 groups based on the different methods
      of vulval reconstruction: (1) simple suture group (6 cases); (2) cutaneous flap
      group (4 cases); (3) myocutaneous flap transposition group (8 cases). The large
      defect area left by radical vulvectomy and inguinal lymphadenectomy was
      reconstructed by myocutaneous flap, tensor fascia latae flap, in 6 cases and
      musculus gracilis myocutaneous flap in 2 cases. All the cases in group 1, 2
      suffered from breakdown of wounds, infection or necrosis, resulting in long term
      hospitalization (mean duration 36.3 days), delayed scar pains, and problems in
      walking or sexual activity. Primary wound-healing was observed in the 6 cases of
      group 3, wound infection occurred in one case with diabetes and one case of
      relapse cancer after radiation therapy. The mean duration of hospitalization in
      group 3 was 20 days, and neither scar pains nor problems in sexual activity was
      found after a follow up of 6 months to 4 years. One case in this group died of
      brain metastases of cancer of vulva. The indications and advantages of
      myocutaneous flap transposition are discussed. It is suggested that myocutaneous
      flap transposition surgery is clinically one of the best and safest methods for
      reconstruction of the vulva and it can improve the quality of life.

PMID- 7648905
TI  - [The study of platinum concentration in retroperitoneal lymph nodes after
      intraperitoneal carboplatin in ovarian tumors].
AB  - Twenty three patients with ovarian tumors were given intraperitoneal carboplatin
      (300 mg/m2) at different times before laparotomy and retroperitoneal
      lymphadenectomy. Total platinum (Pt) concentrations in the nodes, the peritoneum
      and other tissues were measured by flameless atomic absorption spectrometry.
      Histologic examinations were carried out for the nodes. In addition, Total
      platinum concentration of the plasma was determined in 3 cases. Peak Pt
      concentration in retroperitoneal nodes reached at 12 th hour after instillation,
      and the peak value was 13.38 +/- 1.85-21.57 +/- 7.80 micrograms/g, its AUC0-24th
      was 216.8 +/- 9.2-246.4 +/- 32.9 micrograms.h/g. AUC 0-24th for the fatty and
      connective tissues around th e pelvic nodes was 115.6 +/- 40.9 micrograms.h/g; it
      was significantly lower than AUC 0-24th for the nodes. AUC 0-24th for the pelvic
      peritoneum was 1 351.3 +/- 696.5 micrograms.h/g. Peak concentrations in the
      plasma were reached at the second hour after intraperitoneal carboplatin. Its
      peak value and AUC 0-24th were 6.7 +/- 1.0 microgram/L and 61.5 +/- 2.4
      micrograms.h/L respectively. They were obviously lower than those for the nodes.
      These results indicate that after intraperitoneal carboplatin concentrations of
      the drug are higher in the retroperitoneal nodes than in the blood. Post
      chemotherapeutic histological cytodegeneration is found in the lymph nodes in
      some cases.

PMID- 7648906
TI  - [Influence of radioimmunoimaging on the survival rate of ovarian carcinoma
      patients].
AB  - Two groups of patients suffered from ovarian carcinoma were studied
      retrospectively after similar treatments; in one group of 22 patients
      radioimmunoimaging (RII) had been used, which was not used in the other group of
      15 patients. Other factors were similar in the two group such as hospitalization
      period, courses of surgical treatment and regimes of chemotherapy after surgery.
      The staging according to FIGO was also similar in the two groups except that the
      number of patients in stage III was 14 in the RII group but 8 in the non-RII
      group. Neither the age distribution nor the histopathological diagnosis was of
      much difference. 131I labeled monoclonal antibody against ovarian serous
      adenocarcinoma, generated in our laboratory, was given to all patients
      intraperitoneally either before or after the surgery; 7 cases before the initial
      operation, 9 cases before the second look operation and 6 cases for follow up
      after surgery and chemotherapy. The death rates of stage III were 42.9% and 75.0%
      in the RII group and non-RII group respectively. By means of Kaplain Meir's life
      table calculation the 3 year survival rates for the two groups were 63.5% and
      25.0% respectively. The RII group was obviously higher than the non-RII group
      even though not statistically significant. These results were similar to those
      reported in the literature. Three very late cases of ovarian carcinoma were
      reported, in whom RII had been used, are still living after follow-up for more
      than 5 years. The beneficial role of induction of the idiotypic network was
      discussed, and the possibility of innoculation is under investigation.

PMID- 7648907
TI  - [Longitudinal studies of developmental status in term-born infants with
      hyperbilirubinemia].
AB  - Thirty-six infants born at term who developed hyperbilirubinemia were assessed
      for developmental status at 2, 4, 6, 9 and 12 months of age according to a mental
      and psychomotor scale for 0-4 year old. The development quotient (DQ) of infants
      with hyperbilirubinemia were lower than controls, and the reduction was
      significant at 2 months of age (P = 0.03). When single component of DQ was
      compared, it was shown that the DQ score for social behavior was significantly
      lower in patients at 2 months of age than in control (P = 0.007), and except for
      motor, other four single DQ scores were lower in patients than in control and the
      reduction was significant in the DQ scores for adaptability and social behavior
      (P = 0.05, 0.032, respectively). Furthermore, no significant correlation was
      found between DQ and serum peak bilirubin value or duration of
      hyperbilirubinemia. The results indicate that hyperbilirubinemia may have a long
      term impact on mental development of infants. It is necessary to monitor all
      infants with hyperbilirubinemia, including full term infants with no severe
      complication.

PMID- 7648909
TI  - [Screening for gestational diabetes with capillary blood glucose].
AB  - Two hundred and twenty 3rd trimester pregnant women were randomly selected to
      perform 50 g oral glucose tolerance screening test. Simultaneously, both
      capillary and venous blood samples were obtained one hour after the glucose load.
      A high correlation between capillary and venous glucose levels was found (r =
      0.87, P < 0.01). From the receiver operator characteristic curve, it was found
      that the capillary glucose value of 9.1 mmol/L might be defined as abnormal
      threshold value for 100g oral glucose tolerance test (OGTT). The consistent rate
      between capillary and venous glucose test was 91.8%. In 100g OGTT, of 43 cases
      whose venous glucose were > or = 7.8 mmol/L, 11 were diagnosed as gestational
      diabetes mellitus (GDM). All of these 11 patients had capillary glucose > or =
      9.1 mmol/L. This results suggest that the capillary blood glucose test may be
      feasible for screening of gestational diabetes.

PMID- 7648908
TI  - [Prognosis of filial generation from mothers with systemic lupus erythematosus].
AB  - Seventy three pregnancies in 44 women with systemic lupus erythematosus in our
      hospital from June 1970 to June 1993 were studied. It included 15 spontaneous
      abortions (20.55%), 8 induced abortions (10.96%), 9 perinatal fetal deaths
      (12.33%) and 41 live births (56.16%). Therapy with steroids during pregnancy is
      harmless and effective. It may reduce pregnant loss rate. Of 41 live births, 35
      children were followed up (85.36%). Their physical growth, routine blood test and
      urinalysis were normal. There were no definite evidences of mental developmental
      abnormality in children. Two girls had been diagnosed of systemic lupus
      erythematosus at about nine years old. It is possible that systemic lupus
      erythematosus may be hereditable to female filial generation. So we suggest that
      the following-up on children born to mothers with systemic lupus erythematosus
      have to be done till puberty.

PMID- 7648910
TI  - [Cytogenetic analysis of four cases of hermaphroditism].
AB  - On the basis of cytogenetics karyotype analysis, southern blot hybridization
      using sex-determining region of the Y chromosome (SRY) probe and amplified cation
      of the genomic DNA between the SRY code region by specific primers through
      polymerase chain reaction (PCR) have been performed in four cases of
      hermaphroditism. The results showed that, in 1 46, XY female and 1 45, XO/46, XY
      female, the SRY specific hybridization band and PCR amplified band could not be
      detected; in 1 46, XX male, the specific hybridization and PCR band showed SRY
      gene as in normal male; in another true hermaphrodite, the karyotype is 46,
      XX/47,XXY, PCR band is detectable but not hybridization band. The mechanism of
      the abnormal sex differentiation of the cases was analyzed and the two detection
      methods were compared.

PMID- 7648911
TI  - [The regulation of estradiol and progesterone in tumor necrosis factor production
      in vitro].
AB  - The production of tumor necrosis factor (TNF) induced by lipopolysaccharide (LPS)
      in peripheral blood mononuclear cells (PBMC) from normal woman were determined.
      The study investigated the role of regulation of estradiol (E2) and progesterone
      (P) in the production of TNF in-vitro. The results showed that PBMC would produce
      TNF when stimulated by E2 or P in culture in-vitro. The appropriate dosages were
      125 pmol/L in E2 and 10-20 nmol/L in P. The findings suggested that some sex
      hormones could play a regulating role in the production of TNF by PBMC. E2 and P
      may be endogenous substances capable of inducing TNF production. The results
      revealed a beneficial aspect of sex hormones in anti-cancer treatment.

PMID- 7648912
TI  - [Effects of clomiphene on the functions of the corpus luteum].

PMID- 7648914
TI  - [Localized observations of superoxide dismutase by immunohistochemistry in oral
      squamous cell carcinoma tissues].

PMID- 7648913
TI  - [The bond strength of base-etched Co-Cr alloy with resin].

PMID- 7648915
TI  - [Comparative analysis of assaying the 22 kinds of trace elements in human enamel
      of the Uygur and Han nationality with inductively coupled plasma-Auger electron
      spectroscopy].

PMID- 7648916
TI  - [The effect of low engengy laser on the repair of osseous defect in the mandible
      of rabbitis].

PMID- 7648917
TI  - [The application of computor to diagnosing pulpitis].

PMID- 7648918
TI  - [The development of CCD (charge coupled device) scan X-ray cephalometric analysis
      system].

PMID- 7648919
TI  - [Current status and prospects of molecular biology and oral medicine].

PMID- 7648920
TI  - [Flow cytometry analysis of 67 squamous cell carcinoma of the tongue].
AB  - Flowcytometry was used to measure the DNA content in 67 cases with squamous cell
      carcinoma of the tongue. The relationship of FCM resulte are compared with
      clinical and pathological parameters. The results show that the recurrences are
      always appeared within 2 years after operation. Therefore, it is important to
      follow up patient for the first 2 years after operation. 75% of recurrences are
      aneuploidy. With multiple statistic analysis, only the clinical stage and
      aneuploidy are related to lymph node metastasis. The close relative factors to
      recurrence of SCCT are clinical stage, lymph node metastases, DI value and DNA
      ploidy.

PMID- 7648921
TI  - [Masticatory efficiency in skeletal class III malocclusion].
AB  - In this research, we used the Gunne's spectrophotometry method to measure the
      masticatory efficiency in 30 skeletal Class III patients and in 55 normal people.
      After groups comparing and step wise-regression analysis, we found that
      masticatory efficiency in Class III malocclusion group was much lower than that
      in normal occlusion group, and the masticatory efficiency in Class III
      malocclusion was about 60% of that in normal peoples. Masticatory efficiency in
      male was higher than that in female.

PMID- 7648922
TI  - [Radiologic study of ossifying fibroma of the facial and jaw bones].
AB  - 83 cases with ossifying fibroma were diagnosed by clinical, histopathological and
      radiological criteria, and were analyzed radiologically. Four distinct
      radiographic patterns were identified according to the radiodensity and shape:
      (1) cystic radiolucent (42.2%), (2) ground-grass (7.2%), (3) sclerotic change
      (9.6%), (4) mixed change of radiolucent and radiopaque (41.0%). The lesions
      showed a growth pattern of round expanding in all directions with well-defined
      margin and frequent involvement of teeth. A preliminary analysis of the
      relationship among the clinical, radiological and histopathological
      manifestations was presented. The diagnostic criteria was proposed and
      differentiate diagnosis was discussed.

PMID- 7648923
TI  - [Evaluation of radiographic diagnosis on osteoarthrosis of the temporomandibular
      joint].
AB  - 84 cadavers' temporomandibular joints were used to compare the results shown in
      standard lateral tomographs and Schuller's position films with gross views on the
      bone and cartilage changes. The results and conclusions were as follows: (1) The
      positive rates of the radiographic evidences were associated with the degrees of
      the macroscopic lesions. The more severe the macroscopic lesion, the higher the
      positive rate of radiographic evidence. (2) The sensitivity of radiographic
      examination was positively correlated with the extent of the macroscopic lesion.
      So, the negative predictive value was. However, the specificity and the positive
      predictive value of the radiographic examination were negatively correlated with
      macroscopic change index. It has been found that the more the extent of
      osteoarthrosis changes, the higher the sensitivity of radiographic examination;
      the higher the negative predictive values, the higher the positive rate of
      radiographic evidence, and the lower the underdiagnosis rate was. Meanwhile, the
      more the extent of bone pathological changes in the joint, the lower specificity
      of the radiographic examination, and the lower the positive predictive values and
      the misdiagnosis is increased. (3) The radiographic diagnostic value based on the
      standard latreal tomographs of TMJ, Schuller's position films or based on the
      both methods was not satisfied. Its underdiagnosis rate was higher. Therefore, we
      suggest that multiple-layers lateral tomography should be widely used in clinical
      practice.

PMID- 7648924
TI  - [Distribution of masseter afferents and inferior alveolar afferents in trigeminal
      ganglion: probing into the morphological basis for the referred pain between
      teeth and masticatory muscles].

PMID- 7648925
TI  - [Cell kinetics of experimental premalignant lesions of the oral mucosa by Brdu
      labelling].

PMID- 7648926
TI  - [An evaluation of complete denture with the EMG of masseter in chewing cycle].
AB  - The aim of this investigation was to study the EMG of masseter of edentulous
      patients in chewing cycle. 18 subjects were examined by Disa-2000M Neuro
      electromyograph. It was found that the period of chewing cycle of the patients
      with complete denture was distinctly longer than that of normal people, and the
      change of the duration prolongs the time phases. The velocity was relatively slow
      when trying to keep the stability of dentures. The amplitude of potential in
      masseter was lower in chewing cycle, but it did not affect the function of
      mastication. The abnormal pause after occlusal contact of denture had an
      influence on the function of mastication.

PMID- 7648927
TI  - [The three dimensional finite element analysis of fracture in mandibular body
      treated by rigid internal fixations].

PMID- 7648928
TI  - [Anatomical study of anterior branches of the lateral cutaneous nerve of the
      thigh].
AB  - 100 anterior branches of the lateral cutaneous nerve of the thigh were dissected
      and measured in 50 adult cadavers. The results show that this nerve is present in
      all sides. The average length from the point of the nerve piercing fascia lata to
      the point of its first branch is about 79mm, the average width is 2.25 mm, and
      the average thickness is 0.79 mm respectively. It is found that the course of the
      nerve is approximately along the line between the anterior superior iliac spine
      and the midpoint of the patella. This study is benifit to the facial nerve
      grafting in clinic by providing data of the nerve.

PMID- 7648929
TI  - [Hemodialysis and quality of life].

PMID- 7648930
TI  - [Acute renal failure in nephrotic syndrome].

PMID- 7648931
TI  - [Renal osteodystrophy and secondary hyperparathyroidism].

PMID- 7648932
TI  - [Drug therapy of gastrointestinal motility disorders].

PMID- 7648933
TI  - [CT examination for renal vein thrombosis in nephrotic syndrome and the effect of
      thrombolytic therapy].
AB  - Renal vein thrombosis (RVT) was diagnosed in 12 of 60 patients with nephrotic
      syndrome with CT scan and confirmed by selective renal angiography. Of the 60
      patients, 50 had primary glomerulonephritis with various pathological findings
      and 10 lupus nephritis. CT is valuable in screening renal vein thrombosis. Renal
      vein and cubital vein blood in the 12 patients were drawn for assay of FDP, AT
      III, VIIIR: AG, fibrinogen; the results indicated the presence of a state of
      hypercoagulation. Of these, 7 were given 200,000 units of urokinase (UK) in
      divided doses into renal vein within one hour and 5,200,000 units UK into renal
      artery in the same way. Patients also received 2.5mg/d warfarin and 75mg/d
      persantine. Except for the 3 with focal sclerosis, patients received 40mg/d
      prednisone. After 1 month CT and blood fibrinogen, FDP, AT III, VIIIR: AG studies
      were repeated. RVT in patients with intraarterial UK had complete dissolution of
      their thrombi. Complete dissolution occurred in 2 of the 7 receiving UK by renal
      vein and there was partial dissolution in the other 5. It seems that
      intraarterial injection yielded better results. Hypercoagulation state was
      alleviated in all patients with UK therapy.

PMID- 7648934
TI  - [Idiopathic acute renal failure in nephrotic syndrome--a report of 10 cases].
AB  - Ten cases of idiopathic acute renal failure (IARF) in idiopathic nephrotic
      syndrome (NS) were reported. Heavy proteinuria and severe edema were the main
      clinical manifestations in these cases. Sudden oliguria, decrease of urinary
      osmolarity and increase of blood urea nitrogen and creatinine occurred without
      any difinite cause. Pathological examination showed normal or near normal
      glomeruli, diffuse interstitial edema and patchy necrosis of the tubular cells.
      The renal function in all the patients recovered after therapy with diuretics,
      prednisone, etc. It is shown that IARF in idiopathic NS commonly occurred in
      patients with normal or near normal glomeruli, for example, minimal change
      disease (6/10 cases), mild mesangial proliferative glomerulonephritis (4/10
      cass). The incidence of IARF in idiopathic NS was 4.1% (10/245 cases), the IARF
      was mostly reversible.

PMID- 7648935
TI  - [A study on the relative factors for secondary parathyroidosis and renal
      osteodystrophy in long-term hemodialysis patients].
AB  - The authors classified sixty chronic renal failure (CRF) patients receiving
      hemodialysis (HD) treatment into four groups for clinical study. Forty patients
      received HD for more than five years and the remaining twenty patients received
      HD for less than two years. These two groups were further divided into two
      subgroups according to whether they took Rocaltrol or not. The levels of
      parathyroid hormone (PTH), calcitonin (CT), alkaline phosphatase (AKP) and bone X
      ray were studied in each patient. The results showed: the levels of PTH and CT
      were obviously increased in all the patients. The levels of PTH and CT were
      higher in the patients having received HD for more than five years than those for
      less than two years. They were also higher in patients who had not taken Rocatrol
      than those who had. Ninety-five percent of the patients having received HD for
      more than five years had renal osteodystrophy (ROD) without receiving Rocaltrol
      treatment, while only sixty-five percent of the patients developed ROD with
      Rocatrol treatment. The longer the HD time, the higher the ROD incidence. The
      cause, prevention and treatment of ROD were discussed.

PMID- 7648936
TI  - [A study on the relationship between morphology and gene heterogeneity in acute
      promyelocytic leukemia].
AB  - Aucte promyelocytic leukemia (APL) can be treated by all-trans retinoic acid
      (ATRA) with high complete remission rate. 50 cases of APL diagnosed
      morphologically were studied on their cytogenetics, molecular biology and
      response to treatment with ATRA. Forty-five cases showed chromosomal
      translocation t(15; 17) and PML/RAR alpha fusion gene (PML + RAR alpha + APL).
      They had typical morphologic change, in which hypergranular cells appeared more
      frequently in L type of PML/RAR alpha and microgranular cells in S type of
      PML/RAR alpha. Among the 45 PML + RAR alpha + APL patients 8 died early and 37
      had complete remission with ATRA. In the remainging 5 patients, three had typical
      APL morphologic features in cytology, but one of them displayed t (11; 17) with
      PLZF+RARA alpha +, the second showed RAR alpha + PML - (PML - RAR alpha + APL)
      and the third PML - RAR alpha -(PML - RAR alpha - APL). They did not respond to
      ATRA treatment. These data indicate that APL is not a homogeneous disease. The
      other a patients had neither chromosomal translocation nor rearrangements of the
      two genes. On careful morphological reexamination, these two cases were not APL,
      but one of them responded well to ATRA. It is shown that morphology is the
      important diagnostic basis of APL, but in a few APL cases diagnosis should be
      made with the help of cytogenetics and molecular biology. Response of ATRA
      treatment may be of diagnostic value of APL, but is not a specific criterion.

PMID- 7648937
TI  - [Percutanous transluminal coronary angioplasty for unstable angina].
AB  - Percutanous transluminal coronary angioplasty (PTCA) was performed in 190
      patients with 250 diseased vessels and 278 lesions from Dec. 1987 to Feb. 1994.
      All the patients had unstable angina (UA). There were 52 (18.7%) type A lesions,
      175 (62.9%) type B lesions and 51 (18.3%) type C lesions. Of the 190 patients
      undergoing PTCA, 134 (70.5%) patients had dilatation of a single vessel, 46
      (24.2%) of two vessels and 10 (5.3%) of three or more vessels. In 121 patients
      with multivessel disease, 98 (81.0%) had incomplete revascularization of the
      ischemia-related vessel (the culprit vessel) and only 23 (19.0%) had complete
      vessel revascularization. Kissing balloon technique was used in six patients and
      autoperfusion balloon in five. There were four patients undergoing directional
      coronary atherectomy (DCA) and four intracoronary stent. The clinical (patient)
      success rate was 94.7% (180/190) and technical (vessel) success rate 95.2%
      (238/250). The average degree of vessel stenosis was 88.7% +/- 8.3% before PTCA
      and the residual tenosis was 17.9% +/- 9.2% after PTCA. Acute vascular
      complications occurred in 18 (6.5%) lesions. 15 were managed successfully, two
      developed Q wave myocardial infarct and one died. None needed emergency coronary
      bypass operation. PTCA was not successful in 10 patients. In 180 patients with
      successful PTCA, 165 (91.7%) were free from UA, 15 (8.3%) patients had symptoms
      improved and oxygen need reduced. During a six-month follow-up, 26 patients had
      chest pain again with confirmed restenosis, repeated PTCA was performed
      successfully.

PMID- 7648938
TI  - [Analysis of the causes of recurrence of atrioventricular reentry tachycardia in
      patients treated with radiofrequency current ablation].
AB  - The recurrence rate of atrioventricular reentry tachycardia (AVRT) after
      radiofrequency current ablation (RFCA) of 124 accessory atrioventricular pathways
      (AP) in 122 patients were reported and the possible causes of recurrence of AVRT
      were analyzed. Of the 122 patients, 81 were male, 41 female. The average age of
      the patients was 46.3 +/- 14.4 (14-71) hears. There were 81 manifest AP in 80
      patients, 43 concealed AP in 42 patients. 13 of the 124 AP were located in left
      anterior wall, 59 left lateral wall, 8 left posterior wall, 10 left posterior
      interventricular septum. 14 right anterior interventricular septum, 2 mid-septum,
      14 righy posterior interventricular septum and 4 right free wall. All patients
      had no organic heart disease. The total recurrence rate of 124 AP in the 122
      patients during a follow-up period of 2-25 (13.5 +/- 7.1) months was 4.03%
      (5/124), with manifest and concealed AP 1.23% (1/81) and 9.30% (4/43),
      respectively (P < 0.05); left free wall and interventricular septum AP were 2.5%
      (2/80) and 7.5% (3/40), respectively (P > 0.05); left and right AP were 3.3%
      (3/90) and 3.1% (1/32), respectively (P > 0.05). The recurrence time was from 0.5
      to 60 (15.4 +/- 25.4) days. The recurrence may be related to inaccurate ablation
      target site, functional and anatomical characteristics of AP, locations of AP,
      and insufficient ablation energy, etc. It is suggested that AVRT patients
      receiving RFCA should be followed up for a certain period.

PMID- 7648939
TI  - [Detection of hepatitis C virus RNA and C33c antigen in the liver tissue from
      hepatitis C virus infection patients with chronic liver disease].
AB  - To study the distribution of hepatitis C virus (HCV) in liver tissue and its
      pathogenesis, nonisotopic in situ hybridization with a digoxin labelled cDNA
      probe to 5'-NC region of HCV and immunohistochemical study with monoclonal anti
      body of anti HCV C33c were performed on the liver tissue from 24 HCV infection
      patients with chronic liver disease. The results were as follows: In the liver
      tissue of 17 patients with HCV infection (both ELISA anti-HCV and nested PCR HCV
      RNA positive in serum), the positivity of HCV RNA and C33c were 82.3% (14/17) and
      88.2% (15/17) respectively. In 7 patients with anti-HCV positive only HCV RNA was
      not detected in the liver tissue, but 4 out of these 7 cases were C33c positive.
      The specific signals of HCV RNA and C33c were mainly localized in the cytoplasm
      of hepatocytes. The distribution of the HCV infected hepatocytes was spotty,
      scattered or diffuse. There was no relationship between the distribution and the
      level of alanine transaminase or pathologic changes in liver. There were many
      lymphocytes and monoclear cells infitrating the periphery of HCV-infected liver
      cells. The results suggested that replication of HCV in the cytoplasm of
      hepatocytes elicits the host immune response in cells infected with HCV and this
      is important in the pathogenesis of HCV infection.

PMID- 7648940
TI  - [A controlled multi-centre clinical trial on cisapride in treatment of functional
      dyspepsia].
AB  - A controlled multi-centre clinical trial was conducted for evaluating the
      efficacy and safety of cisapride in the treatment of 414 cases of functional
      dyspepsia with 169 cases as control. Cisapride were given 5mg three times daily
      for 4 weeks. The results showed that cisapride could significantly improve the
      symptoms including early satiety, abdominal distention, epigastric pain and
      nausea. Total efficacy rate of cisapride and placebo were 92.99% and 41.42%
      respectively. There were statistically significant difference between the two
      groups. Side-effects are abdominal pain and diarrhoea but most of the patients
      can endure. The above results indicated that the cisapride was safe and effective
      in treatment of functional dyspepsia.

PMID- 7648941
TI  - [A clinicopathological study of cor pulmonale with coronary heart disease].
AB  - The necropsy findings of 18 patients with cor pulmonale and coronary heart
      disease (CHD) were compared with those of a control group of 30 patients with cor
      pulmonale alone. The results showed that there was no significant statistical
      difference between the two groups on average heart weight and average left and
      right ventricular thickness (P > 0.05). The results suggest that at the end stage
      of cor pulmonale left ventricule may be involved whether there are complicating
      left ventricular disease or not. In this study, cor pulmonale and CHD were both
      accurately diagnosed in 33.3%, CHD failed to be diagnosed in 38.9% and cor
      pulmonale failed to be diagnosed in 27.8% of the patients. Single diagnostic
      factor analysis for cor pulmonale with CHD indicated that age, history of
      hypertension, history of angina pectoris, history of MI, accentuation A2,
      presence of bundle branch block, abnormal Q wave and left axis or normal
      deviation, Cheng Xiansheng diagostic criteria and Selvester MI screening criteria
      are of significance (P < 0.05). Multiple factor logistic regression analysis
      indicated that independent prognostic factors including history of angina
      pectoris, Selvester MI screening criteria and Cheng Xiansheng diagnostic criteria
      are of help for diagnosis (P < 0.03-0.000). The above-mentioned diagnostic
      methods are, however, not so specific. At present the best method for diagnosis
      of CHD is coronary arteriography.

PMID- 7648942
TI  - [Report of a case of glucagonoma misdiagnosed as "eczema" and "hepatic angioma"
      for three years and review of literature].
AB  - Glucagonoma is a rare pancreatic tumor, necrolytic migratory erythema is its
      distinctive feature and it is often associated with diabetes mellitus, weight
      loss, anemia, hypoaminoacidemia, glossitis and stomatitis. We reported a case of
      glucagonoma misdiagnosed as "eczema" and "benign hepatic anginoma" for 3 years.
      His blood glucagon level was 1,758 ng/L. The results of abdominal B-mode
      ultrasonography and CT scan were negative, but selected arteriogram showed a
      tumor mass between the pancreatic body and tail. Before operation, treatment with
      octreotide and supply of amino acids were given with improvement of the skin
      lesion. After resection of the tumor from pancreas, necrolytic migratory erythema
      disapeared, but his blood level of glucagon and amino acids did not improve. It
      is suggested that any diabetic patient with chronic skin damage should be checked
      for blood glucagon level. In suspected cases, selected arteriogram will be
      helpful for location of the tumor. Vigorous resection of the pancreatic tumor
      should be done as soon as possible, even though there is already metastases.

PMID- 7648943
TI  - [Serum anti-subtypical Klebsiella pneumoniae antibodies in ankylosing
      spondylitis].
AB  - This study was performed in order to probe the possible pathogenesis of
      Klebsiella pneumoniae (KP) in ankylosing spondylitis (AS). 34 anti-KP antibody
      positive serum samples, including 26 patients with AS, 5 patients with rheumatoid
      arthritis (RA) and 2 healthy individuals, were selected to detect anti-subtypical
      KP antibodies by using an immunoblotting technique. The results showed that the
      number of antigenic bands to KP on nitrocellulose membrane was higher in AS
      patients than in RA patients and healthy individuals. Patients with AS had common
      antibodies response to KP components weight 64,600 (80.7%), 48,200 (61.5%) and
      36,000 (65.4%), patients with RA and healthy individuals had anti-36,000 (75%)
      and anti-30,000 (50%) antibodies. Human anti-HLA-B27 serum and rabbit antisera
      against KP-derived synthetic peptide containing the hexapeptide sequence shared
      by HLA-B27 were able to cross react with 64,600 and 48,200 KP components. Our
      findings suggest that KP might play a role in the pathogenesis of AS by molecular
      mimicry between it and HLA-B27.

PMID- 7648944
TI  - [Lipoprotein(a)--a bridge between blood lipids and fibrinolytic system].

PMID- 7648945
TI  - [Current status and prospects of the study on the prevention and treatment
      diarrheal diseases in China].

PMID- 7648946
TI  - [Studies on diagnostic bacteriophage of Vibrio fluvialis].
AB  - Species of Vibrio fluvialis are identified by their biochemical characteristics
      so far, with a lot of items to be determined, overelaborate procedure and
      expensiveness. Inaccordance with the fact that bacteriophage is a specific
      parasite inhabited in bacteria and has been used in identifying other bacteria
      with high specificity, some of Vibrio fluvialis bacteriophage isolated from
      natural environment were selected to make diagnostic preparation for Vibrio
      fluvialis identification. Diagnostic positivity of Vibrio fluvialis averaged
      84.27%, and 87.84% for those of human source. Cross-lysis rates both for the same
      Vibrio genus and that of different families in the same genus were less then 3%,
      and no cross-lysis was found for the other enteric bacteria in different genera.
      There was no significant difference between diagnostic bacteriophage and
      biochemical tests for Vibrio of unknown species. This method was highly specific,
      sensitive, rapid, simple and inexpensive, and could be used in diagnosis of
      Vibrio fluvialis.

PMID- 7648947
TI  - [Surveillance of diarrhea in children aged under five in Youxian county, Hunan].
AB  - Surveillance analysis of cases with diarrhea in children aged under five years,
      who visited and were treated at village clinics in rural areas of Youxian County
      during June 1992 to May 1993, was conducted. Children aged below five under
      surveillance averaged 1 346, and 223 cases of diarrhea were reported, with a
      reported incidence of 0.17 per person-year. Incidence was higher in 6-month and
      one-year groups with a peak during May to August. But no sex difference of
      diarrhea incidence existed. Use of oral rehydration solution (ORS) accounted for
      87.89% of the cases, with an average of 1.56 packages (each package containing
      500 ml) per case, and 95.52% of dehydrated cases used ORS, with average of 2.02
      packages per case. Use of intravenous rehydration account for 1.79% of the cases,
      58.74% of them used antibiotics and 16.03% of them used more than two kinds of
      antibiotics, and 47.98% of the cases used both ORS and antibiotics. Occurrence of
      blood, mucus and pus in stool accounted for 12.64% of the total cases. All
      indices of surveillance in 1993 improved, compared with those in September 1991.

PMID- 7648948
TI  - [Epidemiological investigation of Campylobacter Jejuni infection in children].
AB  - Epidemiological studies on campylobacter jejuni infection in children were
      carried out in Chengdu during December 1987 to October 1989. Detection rate of
      campylobacter in 1,092 children with diarrhea was 11.36%, with the highest in
      children aged 1-2 and the lowest in babies within six months. Campylobacter
      jejuni could be detected in young children with acute diarrhea all the year
      round, with a higher detection rate in the spring and summer and lower in the
      autumn and winter. Campylobacter jejuni could be detected in 5.09% of healthy
      children, with a significant difference between kindergartens due to their living
      conditions. Use of spectrum of drug-resistance and plasmid analysis in children
      of nurseries and kindergartens to study campylobacter infection suggested
      campylobacter jejuni infection in children could be caused by a lot of distant
      associated strains with genetic homogeneity.

PMID- 7648949
TI  - [Epidemiologic studies on three episodes of acute bacillary dysentery outbreak].
AB  - Three episodes of illness outbreak, with major symptoms of acute abdominal pain
      and diarrhea, occurred in 1990 to 1991 in the army forces stationed in Beijing.
      Bacillary dysentery outbreak caused by Shigella dysentariae were confirmed with
      epidemiological investigations and pathogen identification. Drug sensitivity
      tests with Kirby-Bauer method for the strain isolated showed it had obvious
      resistance to 13 of 14 kinds of antibiotics tested. Detection of plasmid with
      Birnboim method showed most of the strains had R-plasmid of 120-140 Md and few
      had small plasmid. It suggested inherent connection between drug-resistance of
      the strains and plasmid.

PMID- 7648950
TI  - [Detection of carcinogen in source drinking water in stomach cancer prevalent
      areas of Zanhuang county].
AB  - Benzo(a) pyrene, aflatoxin, sterigmatocystin and six kinds of nitrosamine and
      their precursors (secondary amine) in 36 specimens of source drinking water
      collected from stomach cancer prevalent areas of Zanhuang County during the
      autumn and spring periods were determined quantitatively with high performance
      liquid chromatography. Results showed drinking water for local residents was
      significantly contaminated with benzo(a) pyrene, with an average of 0.0148
      microgram/L and the highest one of 0.0305 microgram/L, and especially in the
      autumn, simultaneous contamination with nitrosodimethylamine,
      nitrosodiethylamine, and nitrosodipropylamine could be found, with proportions of
      38.5%, 76.9% and 76.9%, respectively. Aflatoxin B1, and G1 could also be found in
      drinking water in the autumn, but no sterigmatocystin could be detected.

PMID- 7648951
TI  - [Effects of cadmium on calcium homeostasis of isolated epithelial cells of
      proximal renal tubules].
AB  - Changes of intracellular calcium homeostasis in epithelial cell damage of renal
      tubules caused by cadmium and its relationship with the damage were studied in
      isolated tubular cells of rabbits. Results showed levels of free calcium (Ca++)
      in tubular cytoplasm increased significantly with the treatment of cadmium, and a
      series of cellular ultrastructure were damaged. A calcium channel blocker,
      phenothiazine, showed blocking and protecting effects on it. This suggested
      calcium overload played a very important role in kidney damage caused by cadmium.

PMID- 7648952
TI  - [Effects of manganese on learning abilities in school children].
AB  - Manganese in drinking water of Wu Village, Qingchu County, Taiyuan, Shanxi
      Province persisted in an excessive level all the year round, hair and blood
      manganese contents in its primary school pupils, averaged 1.242 micrograms/g and
      617 nmol/L (3.39 micrograms/dl), respectively, were higher than those in normal
      children, and the school records of the former were poorer than those of the
      latter. Levels of serum 5-hydroxytryptamine (5-HT), dopamine, norepinephrine and
      acetylcholine esterase of those 92 school children were determined to study their
      relationship with poor learning abilities. Results showed levels of four
      neurotransmitter in them all were lower than those in control children. School
      records for Chinese language and mathematics correlated positively to the levels
      of most neurotransmitter. Multiple linear regression analysis showed the order of
      the effects of neurotransmitter on school records of Chinese language was 5-HT,
      norepinephrine, acetylcholine esterase and dopamine, and those on mathematics was
      norepinephrine, 5-HT, acetylcholine esterase and dopamine.

PMID- 7648953
TI  - [Studies on inactivation of hepatitis B virus with polymerase chain reaction].
AB  - Polymerase chain reaction-ethidium bromide (PCR-EB) method for detecting
      hepatitis B virus DNA (HBV-DNA) was established with good specificity and a
      detection limit of 1 pg HBV-DNA, minimum HBV infection dose in susceptible
      animal, chimpanzees, could be detected with it. Determination of inactivation of
      HBV-DNA could be inactivated with active chlorine 1,250 mg/L for 60 minutes, or
      2,500 mg/L for 30 minutes, 10 pg HBV-DNA in purified Dane particles could be
      inactivated by active chlorine 625 mg/L for 10 minutes. Accordingly, use of PCR
      to evaluate the effects of chlorine disinfectant in inactivating HBV was
      feasible, and HBV-DNA was a more reliable index for inactivation of HBV than
      HBsAg.

PMID- 7648954
TI  - [Studies on cardiac function in children aged 8-12 with simple obesity].
AB  - Ninety-four obses children and 74 normal controls aged 8-12 were measured
      simultaneously by physiological polygraph, electrocardiograph, phonocardiograph,
      carotid arterial pulse contour and intracardiac impedance differential graph to
      analyze their cardiac function. Results revealed systolic blood pressure,
      diastolic blood pressure, mean arterial pressure, left ventricular ejection time
      and stroke volume in obese children were higher than those in controls, no
      significant difference in cardiac output between them could be seen, and cardiac
      index in the former was lower than that in the latter. It suggested due to
      increase of venous return to the heart and rise of blood pressure in obese
      children, their preload and afterload of the heart increased, cardiac muscular
      contraction strengthened for compensation, cardiac output per unit body surface
      area declined, and part of their cardiac function indexes had been affected.

PMID- 7648955
TI  - [Preliminary studies on protective effects of selenium on human fetal hepatocyte
      in vitro injured by lipid peroxidation].
AB  - A selenium protection model of human fetal hepatocyte in vitro injured by lipid
      peroxidation was established. It was found that survival rate and secretion of
      albumin of the injured cells decreased, and release of alanine transaminase (ALT)
      and its activities in the cells increased, as compared with those in controls,
      with a very significant difference. Under electronic microscope, ultrastructure
      of the injured cells appeared obscure, their membrane and membranous organella
      swelling, or membranous structure breaking. Injuries mentioned above in cells pre
      treated with selenium were obviously decreased and activities of glutathione
      peroxidase increased. But protective effects of selenium supplement were weaker.
      It suggested that preventive supplement with selenium could reduce injury to
      human hepatocyte caused by lipid peroxidation.

PMID- 7648956
TI  - [Advances in the study on cholera immunity and cholera vaccines].

PMID- 7648957
TI  - Heightened visceral sensation in functional gastrointestinal disease is not site
      specific. Evidence for a generalized disorder of gut sensitivity.
AB  - Alteration in visceral sensation locally at the site of presumed symptom origin
      in the gastrointestinal tract has been proposed as an important etiopathological
      mechanism in the so-called functional bowel disorders. Patients presenting with
      one functional gastrointestinal syndrome, however, frequently have additional
      symptoms referable to other parts of the gut, suggesting that enhanced visceral
      nociception may be a panintestinal phenomenon. We measured the sensory thresholds
      for initial perception (IP), desire to defecate (DD), and urgency (U) in response
      to rectal balloon distension, and the thresholds for initial perception and for
      discomfort in response to esophageal balloon distension in 12 patients with
      irritable bowel syndrome (IBS) and 10 patients with functional dyspepsia (FD), in
      comparison with healthy controls. As expected, IBS patients exhibited lower
      rectal sensory thresholds than controls (P < 0.0001), but in addition had
      significantly lower sensory thresholds for both perception and discomfort evoked
      by balloon distension of the esophagus (mean +/- SEM: 8.8 +/- 1.3 ml vs 12.1 +/-
      1.5 ml (P < 0.05) and 12.2 +/- 1.4 ml vs 16.4 +/- 1.4 ml (P < 0.02) respectively.
      Patients with FD showed similarly enhanced esophageal sensitivity, with
      thresholds for perception and discomfort of 8.1 +/- 0.9 ml (P < 0.02), and 10.1
      +/- 1.0 ml (p < 0.001), respectively, but were also found to have sensory
      thresholds for rectal distension similar to those observed in the IBS group,
      significantly lower than in controls: IP 45.0 +/- 17.6 vs 59.3 +/- 1.5 ml (P <
      0.001), DD 98.0 +/- 17.9 vs 298.7 +/- 9.0 ml (P < 0.0001), U 177.2 +/- 25.4 vs
      415.1 +/- 12.6 ml (p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7648958
TI  - An objective measure of stool color for differentiating upper from lower
      gastrointestinal bleeding.
AB  - Subjective reporting of the color of blood passed per rectum has been used to
      predict the location of gastrointestinal bleeding, but the validity of this
      clinical approach has never been evaluated systematically. In this study we
      determined the spectrum of patient and physician descriptors used to characterize
      the color of blood passed per rectum and evaluated prospectively if an objective
      test of stool color would correlate with or improve upon subjective descriptions
      in predicting bleeding locations. The objective test employed was a card
      containing five numbered colors that typify the spectrum of stool blood colors.
      One hundred twenty patients used 23 different descriptors or terms to verbalize
      the color of blood they passed per rectum, and in 22% of cases there was a
      seeming discrepancy between their verbalized color and the color they pointed to
      on the test card. Patients pointing to card color 4 (the black color) resulted in
      closer matching to an upper bleeding source than physicians using terminology
      such as melena or tarry stools. Likewise, patients picking card colors 1 and 2
      (the brightest red colors) resulted in closer matching to a coloanorectal
      bleeding source than physicians using the terms hematochezia or bright red blood
      per rectum (P < 0.02 for each comparison). The positive predictive value of card
      color 4 for an upper bleeding source was very high both when patients pointed to
      this color or when it was determined from the available stool (0.95 and 0.98,
      respectively). The positive predictive value of card color 1 for lower bleeding
      was greater for patients selecting this color than for a direct stool comparison
      (1.00 vs 0.83).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7648959
TI  - Helicobacter pylori status, endoscopic findings, and serology in HIV-1-positive
      patients.
AB  - We have carried out a large prospective study of the frequency of H. pylori
      infection and HIV-1 status in a community of ex-drug abusers including subjects
      with (N = 210) and without (N = 259) upper gastrointestinal symptoms, endoscopy
      and serology. Control groups were patients with upper gastrointestinal symptoms
      not at high risk of HIV-1 infection (N = 219) and asymptomatic blood donors (n =
      322). H. pylori was present in 52% of symptomatic community residents having
      endoscopy and 55% of the control patients with symptoms but not at high risk of
      HIV-1 infection. H. pylori was less common in HIV-1-positive patients (40%) than
      those who were negative (66%; P < 0.001). In patients with AIDS (33%), the
      frequency of H. pylori infection was reduced compared to HIV-1-positive patients
      without AIDS (53%; P = 0.05). All the residents with AIDS had upper
      gastrointestinal symptoms. In community residents, peptic ulcer was always
      associated with H. pylori infection. By H. pylori serology, there was no
      difference in the frequency of infection in asymptomatic residents (56%) whether
      HIV-1 positive (55%) or HIV-1 negative (58%) compared with those residents with
      symptoms. Overall, H. pylori was less common in HIV-1-positive residents (49%)
      than those who were HIV-1 negative (61%; p < 0.05). This difference was due
      mainly to the low frequency of infection in residents with AIDS (33%). H. pylori
      infection is common in HIV-1 positive patients, and only slightly reduced when
      compared with at-risk HIV-1-negative subjects. Peptic ulcer is associated with H.
      pylori in HIV-1 infection.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7648960
TI  - Effect of eradication of Helicobacter pylori infection on gastric epithelial cell
      proliferation.
AB  - Helicobacter pylori infection has been linked with gastric carcinoma. Epithelial
      cell proliferation is an indicator of cancer risk. The aim of this study was to
      assess gastric epithelial cell proliferation before and after eradication therapy
      and to assess the efficacy of treatment of H. pylori infection using lanzoprazole
      and clarithromycin. Twenty-three patients with H. pylori-associated gastritis
      were treated with lanzoprazole 30 mg daily for four weeks and clarithromycin 500
      mg three times a day for two weeks. Antral mucosal biopsies were taken for
      gastric epithelial cell proliferation analysis using the in vitro
      bromodeoxyuridine (BrdU) immunohistochemical technique before and four weeks
      after eradication therapy. Labeling index percent (LI%) was calculated as the
      percent ratio of proliferating cells to the total number of cells in the gastric
      pit. Efficacy of treatment was assessed in 16 subjects. Eight were negative for
      H. pylori infection 28 days after therapy and in eight patients H. pylori
      infection was not eradicated. The eradication rate for the regime was 50%. Cell
      kinetics were assessed in 19 subjects who completed treatment. Patients with H.
      pylori infection had a significantly higher LI% compared to normal (N = 19, LI%:
      5.01 +/- 0.3 vs 3.2 +/- 0.2, N = 29). Eradication of H. pylori infection
      significantly reduced epithelial cell proliferation (N = 9, LI%: 5.2 +/- 0.4 to
      3.2 +/- 0.8, P < 0.001), whereas it was unaltered in those whose infection was
      not eradicated (N = 10, LI%: 4.8 +/- 0.4 to 5.5 +/- 0.5, P = 0.18).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7648961
TI  - Does massive obesity promote abnormal gastroesophageal reflux?
AB  - Fifty consecutive massively obese patients referred for gastroplasty operations
      were prospectively studied to determine the existence of gastroesophageal reflux
      disease by means of a standardized questionnaire, 24-hr ambulatory pH-metry, and
      endoscopy (27 females, mean age 48 years, range 38-57 years). These patients had
      a body mass index (BMI) of 42.5 +/- 5.2 kg/m2 and an actual weight of 125.5 +/-
      17 kg. Heartburn and acid regurgitation was reported by 37% and 28%,
      respectively, mostly of a mild degree (22% and 20%). Dysphagia was reported by
      2%, but none had odynophagia. No patient had any macroscopic esophagitis. The pH
      data were compared with those obtained in 29 age- and sex-matched, symptom-free,
      healthy controls (15 females, mean age 47.6 years, range 30-63 years). During
      ambulatory pH-metry, we recorded a predominance of daytime reflux (7.2 +/- 8.2%
      and total acid exposure of 5.3 +/- 6.4%) in the obese patients, but neither the
      weight, BMI, nor the waist-hip ratio were significantly correlated with any of
      the reflux variables. The pH data obtained from these patients did not, however,
      differ significantly from those recorded in the control population, although a
      somewhat lower daytime acid reflux was found in the latter group. These results
      suggest that massive overweight is not associated with an increased prevalence of
      gastroesophageal reflux disease.

PMID- 7648962
TI  - Nutrient-specific modulation of gastric mechanosensitivity in patients with
      functional dyspepsia.
AB  - Intraduodenal lipid infusion induces symptoms and increases sensitivity to
      gastric distension in patients with functional dyspepsia. To test whether these
      effects are specific for lipid, we compared the effects of intraduodenal
      infusions of either lipid or glucose on symptoms and gastric sensory and motor
      responses to gastric distension. Eighteen dyspeptic patients and nine controls
      were studied. The stomach was distended with a flaccid bag during isocaloric
      infusions (1 kcal/ml) of saline and either 10% Intralipid (nine patients) or
      26.7% glucose (nine patients) into the duodenum. Dyspeptic symptoms and sensory
      thresholds for epigastric fullness and discomfort were assessed. Gastric pressure
      profiles during distensions were similar during lipid and glucose infusions in
      patients and controls, but both were significantly lower than during saline
      infusion. Lower volumes were required to induce fullness and discomfort in the
      patients compared with the controls. In the controls, the threshold volumes
      required to induce fullness and discomfort were greater during infusion of lipid
      and glucose than during saline infusion, but in the patients, the threshold
      volumes were increased during glucose infusion but further reduced during lipid
      infusion. Moreover, in the patients, nausea was more common during lipid than
      glucose infusion and did not occur during saline. The controls did not experience
      any symptoms during any infusion. In conclusion, intraduodenal lipid but not
      glucose sensitizes the stomach to distension in patients with functional
      dyspepsia but not in controls.

PMID- 7648963
TI  - Neural influences on human esophageal and salivary alkali secretion.
AB  - Esophageal secretion HCO3- ions occurs in opossum and man and may contribute to
      mucosal defense. Using a perfusion technique, neuroregulatory influences on
      esophageal and salivary HCO3- secretion were investigated in 24 healthy human
      subjects. The sight and smell of food increased median salivary HCO3- output from
      424 to 573 mumol/15 min (P = 0.014), without significantly altering esophageal
      HCO3- secretion (74-105 mumol/15 min, P = 0.24). Atropine reduced both salivary
      (610 to 68, 17, 10, and 3 mumol/15 min in successive periods; P < 0.028) and
      esophageal HCO3- output (108 to 78, 35, 18, and 7 mumol/10 cm/15 min; P < 0.028,
      respectively. Following atropinization, cholinergic stimulation failed to
      increase salivary secretion but did "unmask" a small rise in esophageal alkali
      output (7 to 27 mumol/10 cm/15 min, P = 0.036), implicating a noncholinergic
      mechanism. Cold-induced pain activated sympathetic reflexes and reduced
      esophageal HCO3- output (91 to 64 mumol/10 cm/15 min, P = 0.041) without
      influencing salivary secretion. These observations support a role for the
      autonomic nervous system in modulating human esophageal and salivary HCO3-
      secretion.

PMID- 7648964
TI  - Morphological evidence of mast cell degranulation in an animal model of acid
      induced esophageal mucosal injury.
AB  - In previous studies we have demonstrated that microvascular permeability
      increases early in the course of experimental acid-induced esophageal mucosal
      injury. This is associated with an increase in the intraluminal appearance of
      histamine, suggesting a possible role for mast cells in this form of injury. In
      the present study, quantitative analysis of esophageal mast cells was undertaken
      using both light and electron microscopy in opossums undergoing intraluminal
      esophageal acid perfusion or normal saline control perfusion. Light microscopy
      showed that animals perfused with either 50 or 100 mM hydrochloric acid had an
      approximate 50% decrease in the number of stainable esophageal mast cells.
      Stereologic analysis of electron micrographs revealed that within the mucosa, the
      mean area of the mast cells as well as nuclear area and area of intact granules
      were also significantly reduced in acid perfused animals. Taken together these
      quantitative morphological analyses suggest that intraluminal acid exposure is
      associated with degranulation and/or lysis of esophageal mast cells and that
      released mediators from esophageal mast cells may play a role in the
      pathophysiology of reflux esophagitis.

PMID- 7648965
TI  - Automatic detection of esophageal pressure events. Is there an alternative to
      rule-based criteria?
AB  - Ambulatory long-term motility recording is used increasingly for evaluation of
      esophageal function. The enormous amount of motility data recorded by this method
      demands subsequent computer analysis. One of the most crucial steps of this
      analysis becomes the process of automatic selection of relevant pressure peaks at
      the various recording levels. Until now, this selection has been performed
      entirely by rule-based systems, requiring each pressure deflection to fit within
      predefined rigid numerical limits in order to be detected. However, due to great
      variations in the shapes of the pressure curves generated by muscular
      contractions, rule-based criteria do not always select the pressure events most
      relevant for further analysis. We have therefore been searching for a new concept
      for automatic event recognition. The present study describes a new system, based
      on the method of neurocomputing. A large sample of normal esophageal pressure
      deflections was used as a "learning set," and the performance of the trained
      neural networks was subsequently verified on different sets of data from normal
      subjects. Our trained networks detected pressure deflections with sensitivities
      of 0.79-0.99 and accuracies of 0.89-0.98, depending on the recording level within
      the esophageal lumen. The neural networks often recognized peaks that clearly
      represented true contractions but that had been rejected by a rule-based system.
      We conclude that neural networks have potentials for automatic detections of
      esophageal, and possibly also other kinds of gastrointestinal, pressure
      variations.

PMID- 7648966
TI  - Role of prostaglandins and histamine in hyperemic response to superficial and
      deep gastric mucosal injury and H+ back-diffusion in cats.
AB  - This study was undertaken to examine the role of prostaglandins and histamine in
      the hyperemic response to gastric mucosal damage followed by H+ back-diffusion.
      Cat stomachs were exposed to 2 mol/liter NaCl for 10 min followed by luminal
      perfusion at pH 1. Hypertonic saline caused extensive (microscopic) damage to the
      surface epithelium, increased gastric mucosal blood flow, and increased release
      of histamine, PGE2, and 6-keto PGF1 alpha (prostacyclin) into portal venous
      blood. The effect of indomethacin and histamine blockers (H1 + H2) on the
      hyperemic response to acid back-diffusion was related to the depth of the mucosal
      injury and the region of the stomach. In the corpus, indomethacin enhanced
      mucosal injury. In areas with superficial damage, the hyperemia was inhibited by
      indomethacin and antihistamines and eliminated by the combination of both. In
      corpus areas with indomethacin-induced deep lesions, the blood flow was very
      high, and this hyperemia was partly inhibited by antihistamines. In the antrum
      the hyperemic response was reduced by antihistamines. Indomethacin increased the
      release of histamine into portal venous blood (baseline recordings) and reduced
      basal gastric mucosal blood flow.

PMID- 7648967
TI  - Induction of cyclooxygenase protein and stimulation of prostaglandin E2 release
      by epidermal growth factor in cultured guinea pig gastric mucous cells.
AB  - The present study was undertaken to investigate whether epidermal growth factor
      (EGF) could stimulate prostaglandin E2 release, and if so, by what mechanism EGF
      would exert such an effect in gastric mucosal cells. In cultured guinea pig
      gastric mucous cells, EGF dose-dependently stimulated prostaglandin E2 release,
      with maximal stimulation observed at 10 ng/ml. EGF stimulated an increase in
      cyclooxygenase activity, which was reduced by protein synthesis inhibitor,
      actinomycin D, and cycloheximide. EGF also stimulated the enzyme protein
      synthesis estimated by Western blot analysis, whereas EGF did not stimulate
      phospholipase A2 activity. These results suggest that such an effect of EGF of de
      novo synthesis of cyclooxygenase protein and prostaglandin E2 release may be
      involved at least in part in the mechanism of EGF-induced local regulation of
      gastric mucosal integrity.

PMID- 7648968
TI  - Ranitidine therapy in patients with idiopathic gastric acid hypersecretion. A
      prospective study.
AB  - One hundred twenty-four patients with idiopathic gastric acid hypersecretion
      (basal acid output greater than 10.0 meq/hr) were prospectively evaluated and
      treated with ranitidine twice a day. Fifty-four patients (44%) required standard
      doses of ranitidine 300 mg/day for adequate treatment, and the other 70 patients
      (56%) required increased doses of ranitidine (mean 994 mg/day, range 600-3000
      mg/day). Mean basal acid outputs for these two groups were 14.0 and 16.6 meq/hr,
      respectively, which were not significantly different. Nevertheless, there was a
      significant correlation between basal acid output and daily ranitidine dose
      required for therapy (r = 0.18, P = 0.05). The duration of ranitidine therapy
      consisted of: < 1 year (N = 46), 1 year (N = 16), 2 years (N = 19), 3 years (N =
      22), 4 years (N = 15), 5 years (N = 6). Only five patients required progressive
      increases in ranitidine during the time of treatment, which consisted of an
      average of 0.5 dose adjustments per year. No side effects occurred with any of
      these high doses of ranitidine. These results indicate that, as in Zollinger
      Ellison syndrome, ranitidine is effective therapy for patients with idiopathic
      gastric acid hypersecretion; however, markedly increased doses as large as 3000
      mg/day may be required.

PMID- 7648969
TI  - Duodenogastric bile reflux and gastrointestinal motility in pathogenesis of
      functional dyspepsia. Role of cholecystectomy.
AB  - To establish the pathogenic role of duodenogastric reflux in dyspeptic symptoms
      we have compared the clinical features, gastrointestinal motility, and rates of
      duodenogastric bile reflux in 12 cholecistectomized dyspeptic patients, 12
      dyspeptic patients with intact gallbladder, and 12 healthy controls. Specific
      symptoms were scored for severity and frequency. Gastrointestinal manometry was
      performed during 3 hr of fasting and 2 hr postprandially. Simultaneously, samples
      of duodenal and gastric contents were obtained sequentially for quantification of
      bile acids. Results show that symptom global severity (9.6 +/- 0.4 vs 8.8 +/-
      0.7) and frequency (9.9 +/- 0.8 vs 9.0 +/- 0.5) were similar in both dyspeptic
      groups; only abdominal pain was milder in cholecystectomized patients (1.9 +/-
      0.1 vs 2.6 +/- 0.2; P < 0.05). Fasting gastric bile acid concentrations were
      higher in cholecystectomized patients (P < 0.05) and antral postcibal motility
      lower (P < 0.05) than in the groups. No relation among gastric hypomotility,
      duodenogastric bile reflux, and symptom scores was detected. We concluded that
      patients with functional dyspepsia and a prior cholecystectomy have clinical
      features similar to those with gallbladders, but some physiological features are
      dissimilar: antral motility is decreased and duodenogastric bile reflux is
      increased. Thus, a uniform clinical expression of various pathophysiological
      disturbances constitutes the basis of functional dyspepsia.

PMID- 7648970
TI  - Ampulla of Vater/duodenal wall spasm diagnosed by antroduodenal manometry.
AB  - Patients with chronic epigastric to right upper quadrant pain are often
      considered to have gallbladder of sphincter of Oddi dysfunction, but standard
      tests are nondiagnostic. In 62 consecutive patients with this compliant
      undergoing antroduodenal manometry, we correlated a change on duodenal motility
      with spasm of the ampulla of Vater/duodenal wall. This distinctive motility
      pattern occurred and was analyzed in 35% of patients. It is characterized by
      increased duodenal wall tone with phasic contractions of 19-22 or 41-44
      contractions/min or by phasic activity alone. The subjects with spasm also
      underwent cholecystokinin cholescintigraphy, and 50% showed either significantly
      delayed gallbladder emptying of hilum to small intestine emptying, or both. The
      disorder appears to be secondary to a loss of neural inhibitory control and a
      dysfunctional small-bowel pacemaker. Antroduodenal manometry is an essential
      diagnostic procedure that complements sphincter of Oddi manometry in evaluation
      of unexplained right upper quadrant pain.

PMID- 7648971
TI  - Blood flow and mucoid cap protect against penetration of carcinogens into
      superficially injured gastric mucosa of rats.
AB  - In this study we tested the influence of blood flow and the mucoid cap on the
      penetration of carcinogens to the proliferative cells in the injures rat gastric
      mucosa. Ten minutes after mucosal exposure to 4.5 mol/liter NaCl, N-[3H]methyl-N'
      nitro-N-nitrosoguanidine was instilled intragastrically. Hypertonic saline caused
      superficial mucosal damage, formation of a mucoid cap, high gastric mucosal blood
      flow, and a large flux of fluid into the gastric lumen. The mean percentage of S
      phase cells labeled with carcinogen (the cell population at risk for N-methyl
      N'nitro-N-nitrosoguanidine-induced carcinogenesis) in the antrum and corpus was
      0.2 and 0.2, respectively, in the injury control group, 10.1 and 2.0 after
      removal of the mucoid cap, 1.5 and 9.8 after celiac artery ligation, and 28.2 and
      21.9 after removal of the mucoid cap and celiac artery ligation. These results
      show that both the mucoid cap and gastric mucosal blood flow protect against
      penetration of carcinogens into the superficially injured gastric mucosa.

PMID- 7648972
TI  - Inhibition of endogenous nitric oxide reduces basal mesenteric vascular tone but
      does not alter intraduodenal hydrochloric acid-induced intestinal hyperemia in
      rats.
AB  - There are conflicting reports on the role of endogenous nitric oxide (NO) in the
      regulation of basal intestinal blood flow. The effect of inhibition of NO in
      intraduodenal hydrochloric acid (HCl) induced intestinal hyperemia remains to be
      confirmed. We investigated the effect of inhibition of endogenous NO on basal
      intestinal blood flow, HCl-induced intestinal hyperemia, and duodenal villous
      injury. Superior mesenteric artery blood flow in rats was measured by pulsed
      Doppler flowmetry and duodenal villous injury evaluated by histology. Intravenous
      NG-nitro-L-arginine methyl ester (L-NAME), or L-arginine or D-arginine followed
      by L-NAME, was given to show inhibition, reversal of inhibition of endogenous NO
      synthase, and stereospecificity, respectively. An intraduodenal 2 ml/kg bolus or
      perfusion for 30 min of 0.1 N HCl was given 15 min after L-NAME or vehicle. Mean
      arterial blood pressure was increased by L-NAME, which also significantly reduced
      intestinal blood flow under basal condition and after intraduodenal HCl. Basal
      mesenteric blood flow was not altered by L- or D- arginine. The L-NAME-induced
      increase in blood pressure and decrease in basal blood flow was attenuated by L-
      but not D-arginine. The villous damage and the magnitude of the peak hyperemia
      was unchanged by L-NAME, L- or D-arginine. Inhibition of endogenous NO by L-NAME
      is suggested by the significant rise in blood pressure. The rise in blood
      pressure and reduction in blood flow are attenuated by L- but not D-arginine,
      indicating stereospecificity. Inhibition of endogenous NO reduces basal
      mesenteric vascular tone but does not alter intraduodenal HCl-induced intestinal
      hyperemia.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7648973
TI  - Luminal dopamine modulates canine ileal water and electrolyte transport.
AB  - Previous studies have suggested that dopamine stimulates active ileal ion
      absorption via alpha 2-adrenergic or dopaminergic receptor activation.
      Identification of a dopamine 1a receptor on rat enterocytes located in intestinal
      crypts prompted this investigation of the effect of luminally administered
      dopamine on water and ion transport in the canine ileum. Absorption studies (n =
      27) were performed in dogs with 25-cm ileal Thiry-Vella fistulas. Perfusion with
      [14C] PEG was used to calculate absorption of water and electrolytes from the
      Thiry-Vella fistula. Experiments consisted of three 1-hr periods: basal, luminal
      drug infusion at 10(-4) M, and recovery. Agonists used included dopamine (DOP:
      alpha-adrenergic, D1 and D2 receptor) and SKF 38393 (D1 receptor). Antagonists
      used included terazosin (TZ: alpha 1) and yohimbine (YOH: alpha 2). DOP caused
      significant increases in water and electrolyte absorption. TZ and YOH prevented
      the dopamine-induced proabsorptive response. Luminal DOP may serve as a
      proabsorptive modulator of ileal transport, acting via alpha 1, alpha 2, and
      dopaminergic receptors. The development of more potent proabsorptive dopamine
      analogs, which maintain the ability to broadly activate mucosal receptors, may be
      useful in such clinical situations as diabetic diarrhea, short gut syndrome, or
      following small bowel transplantation.

PMID- 7648975
TI  - Soluble interleukin-2 receptor in Crohn's disease. Assessment of disease activity
      and prediction of relapse.
AB  - In Crohn's disease, the activity of the disease is difficult to evaluate and the
      evolution of the disease is difficult to predict. The soluble interleukin-2
      receptor serum level has been reported to correlate with clinical activity of the
      disease and with mucosal immune activation. We compared serum soluble interleukin
      2 receptor to classical inflammatory markers and other immune parameters in the
      assessment of clinical disease activity and prediction of relapse in patients
      with Crohn's disease. Soluble interleukin-2 receptor serum levels correlated well
      with the Crohn's disease activity index, and multivariate analysis showed that
      this correlation was independent of the other inflammatory and immune markers.
      The correlation was not greater, However, than that between some inflammatory
      markers, such as ESR, and Crohn's disease activity index. Longitudinal follow-up
      showed that a high soluble interleukin-2 receptor serum level was highly
      predictive of relapse. Multivariate analysis showed that the soluble interleukin
      2 recepteur serum level was complementary to other inflammatory and clinical
      markers in the prediction of relapse of disease. We conclude that soluble
      interleukin-2 receptor is of use in monitoring Crohn's disease, particularly in
      prediction of relapse.

PMID- 7648974
TI  - Interleukin-7 activates intestinal lymphocytes.
AB  - Human intestinal lymphocytes, particularly intraepithelial lymphocytes,
      proliferate minimally to some agents, like mitogens and stimuli of the CD3
      pathway. This in vitro finding may be due, in part, to a loss of factors found in
      vivo. Three T-cell growth factors, IL-7, IL-9, and IL-12, were tested for their
      ability to stimulate the proliferation of intestinal lymphocytes. Both
      intraepithelial lymphocytes and lamina propria lymphocytes proliferated more
      vigorously to IL-7 than to IL-9 or IL-12, and only IL-7 increased stimulation
      through the CD3 pathway. The IL-7-induced response was IL-2-dependent: IL-2
      receptors appeared on both intestinal lymphocyte types, and antibody to the IL-2
      receptor blocked IL-7-induced proliferation. Both CD4+ and CD8+ T-cell subsets
      responded to this cytokine as shown by phenotype-depletion experiments and
      constancy in the CD4/CD8 ratios after culture with IL-7. In addition, the T-cell
      receptor alpha beta and gamma delta subsets responded equally well to IL-7. This
      newly described selective proliferative response of intestinal lymphocytes to IL
      7, but not to IL-9 or IL-12, requires no preactivation and may enhance growth in
      vivo.

PMID- 7648976
TI  - Lack of crucial role of mast cells in pathogenesis of experimental colitis in
      mice.
AB  - Mast cell alterations have been implicated in the pathogenesis of chronic
      ulcerative colitis (UC). We studied the effect of mast cell deficiency of the
      severity of inflammation in a murine model of colitis. Colitis was induced in
      mice using dextran sodium sulfate (DSS). Mast-cell-deficient mice (WBB6F1/J-W/WV;
      N = 17) and normal littermates (WBB6F1/J-+/+; N = 17) were administered DSS 4%
      w/v for seven days, then water alone for one week, followed by 5% DSS for six
      days. Animals were sacrificed at the end of the protocol. Segments of proximal,
      mid-, and distal colon of each animal were processed for histopathological
      examination. Mortality and morbidity (diarrhea and weight loss) for each group
      were assessed. There was no significant difference between the two groups in
      either their clinical parameters (mortality and morbidity) or the severity of
      colitis as graded histopathologically. Our findings suggest that mast cells are
      not crucial for the development of DSS-induced colitis.

PMID- 7648977
TI  - Comparison of bowel patterns in Hispanics and non-Hispanic whites.
AB  - Survey questionnaires can be used to characterize normal bowel habits and the
      prevalence of bowel dysfunction. To determine whether ethnic and sex-related
      differences in bowel patterns exist between Hispanics and non-Hispanics whites,
      we conducted a survey of a nonpatient population in El Paso, on the U.S.-Mexico
      border. A forced-choice, self-report questionnaire was distributed to 1014
      subjects and returned by 1000. Data from the 905 Hispanic and non-Hispanic white
      subjects were compared. Stool frequency was analyzed by multiple linear
      regression, and bowel dysfunction variables were analyzed by stepwise logistic
      regression, in ethnic and sex groups. Data were also analyzed controlling for
      age, socioeconomic status, dietary factors, and use of laxatives. There was a
      significant sex difference in mean number of stools per week reported (P <
      0.0001): Hispanic males greater than Hispanic females (8.6 vs 7.5) and non
      Hispanic white males greater than non-Hispanic white females (9.3 vs 7.2). The
      frequency of irritable bowel syndrome-type symptoms was greater in females than
      in males (23.4% vs 9.6%, P < 0.001) and was less in Hispanics than non-Hispanic
      whites (16.9% vs 21.8%, P < 0.05), but a significant ethnic difference was not
      found after controlling for covariates. Additionally, females reported more
      alternating bowel pattern (44.0% vs 28.5%, P < 0.001) and constipation (25.5% vs
      12.4%, P < 0.01) than males, and non-Hispanic white females more abdominal pain
      than the other subgroups (P < 0.05). Ethnic differences in dietary factors that
      may be relevant to bowel function were identified.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7648978
TI  - Prevalence of previously undiagnosed gallstones in a population with multiple
      risk factors.
AB  - This study was aimed at investigating whether it is possible, on the basis of the
      presence of multiple factors, to select a population with a higher prevalence of
      gallstones than that predicted simply on the basis of age and sex. Thus, we
      selected and screened for the presence of previously undiagnosed gallstones
      subjects with at least four of the following variables: female sex, age over 40,
      obesity, diabetes, biliary colic, family history of gallstones or
      cholecystectomy, hypertriglyceridemia, parity, and oral contraceptive use. The a
      priori probability (or expected prevalence) of having previously undiagnosed
      gallstones was calculated for each subject on the basis of sex and age according
      to data derived from epidemiological studies performed in Italy in the general
      population. Among the 821 males and 3930 females participating in this study,
      previously undiagnosed gallstones (GS) were found in 135 (16.4%) males and 691
      (17.6%) females. The ratio between observed and expected prevalence of GS was
      higher in males (3.09) than in females (2.32). The highest ratios between
      observed and expected prevalence of GS were found in the lowest classes of
      expected prevalence in both sexes. The best predictors of the presence of GS were
      age, biliary colic, and diabetes in males and age, biliary colic, obesity, and
      number of pregnancies in females. It is concluded that selection of subjects with
      multiple factors associated with GS increases the a priori probability of GS
      diagnosis by a factor 2 in females or 3 in males. Stricter selection criteria
      should be used for females.

PMID- 7648979
TI  - Gallstone recurrence after direct contact dissolution with methyl tert-butyl
      ether.
AB  - To determine the rate and characteristics of gallstone recurrence after direct
      contact dissolution with methyl tert-butyl ether, 60 consecutive patients were
      followed for up to 4.5 years (median 2.2 years) after complete disappearance of
      all stone residues and debris and cessation of adjuvant bile acid therapy.
      Initial gallstones had been multiple in all but four patients. Twenty-eight of
      the 60 patients developed recurrent gallstones. The cumulative risk of gallstone
      recurrence (actuarial analysis) was 23 +/- 6%, 34 +/- 7%, 55 +/- 8%, and 70 +/-
      9% at one, two, three, and four years, respectively. The recurrent stones were
      usually multiple and small (6 +/- 4 mm). Gallstone recurrence was associated with
      recurrent biliary pain in two patients, one of whom developed acute
      cholecystitis. Recurrent stones were cleared completely by bile acid medication
      with or without shock-wave lithotripsy in 61 +/- 15% of patients at one year
      (actuarial analysis). In conclusion, gallstone recurrence after successful
      contact dissolution of multiple stones with methyl tert-butyl ether has to be
      expected in a high percentage of patients. Most patients, however, remain free of
      biliary pain during long-term follow-up.

PMID- 7648980
TI  - Effect of aspirin on gallbladder motility in patients with gallstone disease. A
      randomized, double-blind, placebo-controlled trial of two dosage schedules.
AB  - Patients with gallstone disease have impaired gallbladder motility.
      Prostaglandins are thought to be important mediators of gallbladder hypomotility.
      We assessed the effect of aspirin, a prostaglandin inhibitor on gallbladder
      resting volume and ejection fraction according to a double-blind study protocol
      in 20 healthy volunteers and 30 patients with gallstone disease. Healthy
      volunteers had a higher ejection fraction compared to patients with gallstone
      disease (73.9 +/- 0.9% vs 60.4 +/- 1.0%, P < 0.05). Aspirin in a dose of 350
      mg/day for two weeks did not alter gallbladder motility in the healthy
      volunteers. Thirty patients with gallstone disease were randomized into three
      treatment groups: group I (placebo), group II (aspirin 350 mg/day), and group III
      (aspirin 1400 mg/day). After two weeks of treatment, gallbladder ejection
      fraction was improved in group II (74.0 +/- 1.7% vs 62.0 +/- 1.7%, P < 0.01) and
      group III (69.8 +/- 3.8% vs 61.2 +/- 1.3%, P < 0.01) but not in group I (60.4 +/-
      2.6% vs 59.0 +/- 1.9%, P = NS). The higher dose of aspirin did not induce a
      greater increase in gallbladder emptying. It is concluded that impaired
      gallbladder motility in patients with gallstone disease is corrected by short
      term oral aspirin even in low dosage. This may be clinically useful in secondary
      prophylaxis after nonsurgical therapy for gallstone disease.

PMID- 7648981
TI  - Biliary alpha 1-acid glycoprotein concentrations in gallstone-free controls and
      in patients with multiple or solitary cholesterol gallstones.
AB  - We recently identified a promoting glycoprotein in the concanavalin A-bound
      fraction of gallbladder bile as a biliary form of alpha 1-glycoprotein (AAG). The
      concentration of biliary AAG appears to exert an important promoting effect on
      the speed of cholesterol nucleation in many patients with cholesterol gallstone
      disease. In the current study, we provide information about the biliary
      concentration of AAG as well as the amount and comparative potency of its
      subfractions in patients with and without cholesterol gallstone disease. The
      amount of total biliary AAG and the amounts of its different isoforms separated
      by concanavalin A affinity chromatography were measured by ELISA. Estimates of
      absolute concentrations of AAG for each sample were normalized to the sample
      total protein content to give relative AAG values. The promoting activity
      (potency) of immunopurified biliary AAG from gallstone patients and gallstone
      free controls on cholesterol crystallization was compared by a crystal growth
      assay. The mean absolute concentration of AAG in gallstone-free controls was not
      significantly different from multiple stone patients. The relative concentration
      of AAG (micrograms per milligram total protein) was significantly increased in
      patients with multiple stones when compared to controls (P < 0.05), and both the
      absolute and relative concentrations of AAG (micrograms per milligram bile), were
      three- and to five fold higher in a number of these patients. The functional
      activity and distribution of AAG in different subfractions was similar in
      gallstone patients and gallstone-free controls. The relative concentration of
      biliary AAG is significantly greater in cholesterol gallstone patients with
      multiple stones than in gallstone-free controls.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7648982
TI  - Mechanisms of biliary excretion of lithocholate-3-sulfate in Eisai
      hyperbilirubinemic rats (EHBR).
AB  - Biliary excretion of lithocholate-3-sulfate is markedly impaired in EHBR. To
      examine the mechanism of biliary lithocholate-3-sulfate excretion in EHBR, the
      effects of colchicine treatment, a vesicular transport inhibitor, and infusion of
      taurocholate and organic anions were studied in EHBR and Sprague-Dawley rats.
      Colchicine treatment and taurocholate infusion had no effect of biliary
      lithocholate-3-sulfate excretion in EHBR, suggesting that biliary lithocholate-3
      sulfate excretion is not mediated by the vesicular transport or by the bile acid
      excretory pathway. In control Sprague-Dawley rats, both sulfobromophthalein and
      dibromosulfophthalein infusion inhibited biliary lithocholate-3-sulfate
      excretion. In contrast, in EHBR dibromosulfophthalein infusion inhibited biliary
      lithocholate-3-sulfate excretion but BSP infusion did not. Indocyanine green and
      pravastatin infusion did not affect biliary lithocholate-3-sulfate excretion but
      pravastatin infusion had no effect in EHBR. These findings indicate that, whether
      physiologically important or not, two of more excretory pathways for organic
      anions exist at the canalicular membrane other than the ATP-dependent one.

PMID- 7648983
TI  - Intestinal transit and bacterial translocation in obstructive pancreatitis.
AB  - Pancreatic infection from gut-derived bacteria has emerged as the major cause of
      death in necrotizing pancreatitis. Bacterial overgrowth of indigenous enteric
      organisms as a consequence of guts stasis (ileus) represents a potential initial
      event in this process. The present study was designed to examine the
      interrelationships between intestinal transit, enteric bacteriology, and the
      translocation of bacteria from the gut lumen to mesenteric lymph nodes and
      splanchnic viscera during experimentally induced acute pancreatitis. Male rats
      underwent pancreaticobiliary duct ligation (PBDL) or sham surgery and were
      sacrificed after 24, 48, or 96 hr. Severity of pancreatitis was assessed with
      histology, tissue water content, and amylase and lipase levels. Intestinal
      transit was measured with fluorescent tracers. Blood, mesenteric lymph nodes
      (MLNs), splanchnic organs, and gut luminal contents were subjected to
      bacteriologic analysis. PBDL was followed by biochemical and histologic evidence
      of progressive pancreatic injury at each time interval. Enteric bacteria within
      the gut and in adjacent MLNs increased as intestinal transit decreased after PBDL
      induced pancreatic inflammation. Surprisingly, all parameters returned to control
      levels by 96 hr in spite of progression of pancreatic inflammation.

PMID- 7648984
TI  - Prognosis and life expectancy in chronic liver disease.
AB  - The aim of the present was to define prognosis and life expectancy in patients
      with chronic liver disease of different etiologies and to relate them to an age-
      and sex-matched normal population. After a follow-up of 15 years, life expectancy
      of 620 patients with chronic liver disease was retrospectively calculated and
      compared with an age- and sex-matched normal population. Among patients with
      cirrhosis, prognosis was dependent upon Child classification (P = 0.001).
      Patients with alcoholic cirrhosis and fatty liver disease were younger (P = 0.01)
      and had a lower life expectancy than patients with other causes of chronic liver
      disease (P = 0.004). Patients with hepatitis B and hepatitis C cirrhosis showed a
      comparable prognosis and a significantly lower life expectancy than the age- and
      sex-matched population. Cryptogenic and autoimmune liver diseases showed a
      comparable life expectancy but a significantly shorter life expectancy than the
      normal population. In patients with alpha 1-antitrypsin deficiency-associated
      cirrhosis, a high viral coinfection rate was found (P = 0.01). For patients with
      noncirrhotic hemochromatosis, prognosis was poorer than that for the age- and sex
      matched population. In patients with asymptomatic primary biliary cirrhosis,
      chronic persistent hepatitis B, and alpha 1-antitrypsin deficiency without
      cirrhosis, life expectancy was equal to that of the normal population. Prognosis
      and life expectancy in chronic liver disease depend on stage, cause, and symptoms
      of chronic liver disease; age; and possibilities of treatment. In patients with
      hereditary liver disease, additional viral infection of alcohol abuse lead to a
      significant deterioration of life expectancy. Patients with alcoholic chronic
      liver disease have the poorest prognosis.

PMID- 7648985
TI  - Glucagon, stress, and portal hypertension. Plasma glucagon levels and portal
      hypertension in relation to anesthesia and surgical stress.
AB  - Glucagon has been proposed as the mediator of splanchnic hyperemia in portal
      hypertension. Employing an assay specific for pancreatic glucagon, we reevaluated
      the relationship between this peptide and portal hypertension in the portal vein
      (PV)-stenosed rat model addressing, in particular, the effects of anesthesia and
      surgical stress. Plasma glucagon levels were similar in sham-operated and portal
      hypertensive rats: glucagon, sham vs PV stenosed: 110.7 +/- 17.1 pmol/liter vs
      140.6 +/- 23.3 pmol/liter (NS). Furthermore, plasma levels of glucagon and the
      related peptide VIP were not significantly influenced by anesthesia or surgical
      stress, and levels remained similar under all conditions in sham-operated and PV
      stenosed animals. We conclude that pancreatic glucagon is not elevated in the PV
      stenosed rat; differences between these results and those describing
      hyperglucagonemia in this model cannot be explained on the basis of a
      differential response to stress but may reflect differences in glucagon assay
      system.

PMID- 7648986
TI  - Questioning the clinical significance of upper gastrointestinal cytomegalovirus
      disease following heart transplantation.
AB  - We performed a retrospective review of patients who underwent
      esophagogastroduodenoscopy after heart transplantation to determine the clinical
      setting in which upper gastrointestinal cytomegalovirus disease is identified. No
      gastrointestinal cytomegalovirus disease was found prior to transplant 51 and
      this period (from transplant 1 to 50) correspond to a time when significantly
      fewer esophagogastroduodenoscopies included biopsy. Patients in whom
      cytomegalovirus was identified were more likely to have been CMV seronegative and
      to have received a heart from a seropositive donor (60% vs 20%, P = 0.029). In
      addition, patients with cytomegalovirus used aspirin more commonly (90% vs 31%, P
      = 0.001), and underwent esophagogastroduodenoscopy earlier after transplantation
      (123d vs 652d, P = 0.029). We conclude that factors that increase the use of
      esophagogastroduodenoscopy and biopsy in the early transplant period increase the
      likelihood of identifying cytomegalovirus in gastrointestinal tissue. However,
      the clinical course and significance of cytomegalovirus identified in the upper
      gastrointestinal tract in heart transplant patients may be difficult to discern.

PMID- 7648987
TI  - Chemotactic factors released from hepatocytes exposed to acetaminophen.
AB  - To clarify the mechanism of neutrophil infiltration in the liver of acetaminophen
      induced hepatic injury, chemotactic factor released from hepatocytes exposed to
      acetaminophen has been investigated. Hepatocytes exposed to acetaminophen release
      nondialyzable chemotactic factor, although acetaminophen in itself inhibits
      chemotaxis of neutrophils. Chemotactic activity of the nondialyzable chemotactic
      factor was reduced after treatment with heat (56 degrees C, 30 min) or trypsin.
      Chemotactic activity was demonstrated at the molecular weights of around 25 and
      55 kDa. Chemotactic activity of the conditioned medium was not significantly
      reduced in the presence of antibody against rat KC/gro protein (interleukin-8
      related cytokine in rodent). Chemotactic activity of a 25-kDa factor was reduced
      by the antibody against the antibody against KC/gro protein, but that of a 55-kDa
      factor was not reduced. Immunoblot analysis revealed that the peptide reacted
      with antibody against rat KC/gro protein was demonstrated at a molecular weight
      of around 20-25 kDa, but not around 55kDa, when the conditioned medium of
      acetaminophen-treated hepatocytes was electrophoresed. These results suggest that
      hepatocytes exposed to acetaminophen release two types of chemotactic factors for
      neutrophils and that a major part of the chemotactic factor could be different
      from a member of interleukin-8 family.

PMID- 7648989
TI  - Development of transient autoimmune hepatitis during interferon treatment of
      chronic hepatitis B.
AB  - A 42-year-old man was treated with interferon-alpha for chronic hepatitis B;
      during the fourth week of treatment he developed an exacerbation of liver
      disease, and nuclear and smooth muscle autoantibodies, which were previously
      negative, were detected in very high titers. After discontinuation of interferon
      therapy, ALT values subsided promptly and autoantibodies disappeared within a few
      months. This sequence of events strongly suggests a direct relationship between
      IFN treatment and a self-limited hepatitis with autoimmune markers in this case.

PMID- 7648988
TI  - Serum levels of soluble interleukin-2 receptors and effects of interferon-alpha
      for patients with chronic hepatitis C virus.
AB  - To characterize the role of serum soluble interleukin-2 receptor (sIL-2R) in
      hepatitis C virus (HCV) infection, the level of sIL-2R was measured by ELISA in
      117 subjects with chronic HCV infection and in 23 healthy controls. HCV RNA was
      detected by polymerase chain reaction in all subjects with HCV infection. Forty
      seven patients with chronic hepatitis and 10 with liver cirrhosis were treated
      for six months with natural interferon-alpha. The sIL-2R levels of 40
      asymptomatic HCV carriers (632 +/- 340 units/ml), 47 patients with chronic
      hepatitis (547 +/- 204 units/ml), 10 with cirrhosis (679 +/- 239 units/ml, and 20
      with hepatocellular carcinoma (1145 +/- 487 units/ml) were significantly higher
      than those of healthy controls (380 +/- 191 units/ml) (P < 0.05, respectively).
      The levels of sIL-2R increased, as did the histological activity index scores (r
      = 0.348, P < 0.01). The level of sIL-2R rose after the initial administration of
      interferon in all 57 patients. In patients whom HCV RNA was eliminated from the
      sera within a six-month follow-up after cessation of treatment, the level of sIL
      2R reverted to basal values, but in patients in whom HCV RNA was not eliminated
      the value was significantly higher than that before treatment. These results
      suggest that monitoring serum sIL-2R in patients with chronic HCV infection
      treated with interferon may provide information concerning the possibility of the
      elimination of HCV RNA.

PMID- 7648990
TI  - Liver injuries induced by herbal medicine, syo-saiko-to (xiao-chai-hu-tang).
AB  - Four patients treated with the herbal medicine syo-saiko-to (xiao-chai-hu-tang)
      exhibited acute drug-induced liver injury. The latent period was one and a half
      to three months. All of the patients showed a rise in aminotransferases after
      readministration or challenge test. The liver histology revealed centrilobular
      confluent necrosis or spotty necrosis, microvesicular fatty change, acidophilic
      degeneration, and a granuloma. Cholestasis was seen in two patients. The results
      of the [13C]aminopyrine breath test, performed in one patient, were low before
      the challenge test and even lower after the challenge. These findings suggest
      that the herbal medicine syo-saiko-to may induce acute injury or the
      hepatocellular pattern with variable cholestasis.

PMID- 7648992
TI  - Nutritional assessment of drug addicts.
AB  - OBJECTIVE: To discern if factors such as organic pathology, sex, duration and/or
      intensity of drug addiction, alcohol abuse, hepatitis B infection, anorexia with
      poor food and drink consumption, or disturbance of social and familial networks,
      are related to an impaired nutritional status in hospitalized drug addicts.
      DESIGN: Cross-sectional prospective study. SETTING: Detoxication unit and
      internal medicine unit of a university hospital. PATIENTS: 140 drug addicts
      without acute organic pathology and 18 with acute organic pathology related to
      drug addiction. The immunological study was compared with a control group
      composed of 50 healthy and well-nourished individuals (26 women and 24 men), age
      matched with our patients. RESULTS: Drug addicts without organic pathology were
      under-nourished: 92.4% weighed under the mean weight for the population and 55.7%
      had had a weight loss above 5%. The distribution of mid-upper arm circumference
      (MUAC), triceps skinfold (TSF) measurement and mid-arm muscle area (MAMA)
      compared with the percentiles for the population showed a shift towards lower
      values. We found a high percentage of patients with a high lymphocyte count
      (55%). Despite the high lymphocyte count, delayed hypersensitivity was depressed
      in our patients. Of our patients, 66.4% exhibited anorexia at admission. The mean
      calorific intake was 978 +/- 89 kcal/day in females and 1265 +/- 64 kcal/day in
      males. However, in most cases, malnutrition (usually marasmus-like malnutrition)
      was not very severe; only 30% of the drug addicts weighed less than 80% of the
      mean weight for the population, or admitted to a weight loss above 10%, and by
      subjective nutritional assessment, only 18% were deeply malnourished. Otherwise,
      the nutritional status was very poor in drug addicts with acute organic
      pathology. We also found a worse nutritional status in our patients related to
      female sex, intensity of drug addiction, anorexia with poor food and drink
      consumption, and disturbance of the social and familial networks. CONCLUSIONS:
      Many drug addicts suffer from calorie and protein malnutrition. This mainutrition
      is related to female sex, intensity of drug addiction, anorexia and poor food and
      drink consumption, and disturbance of the social and familial links. Acute
      organic pathology leads to a significant worsening of the nutritional status of
      drug addicts.

PMID- 7648991
TI  - Using social network analysis to study patterns of drug use among urban drug
      users at high risk for HIV/AIDS.
AB  - Few studies have examined the current social relationships of injecting drug
      users. This paper examines the structural and relationship characteristics of the
      social networks of injecting drug users, and the relation of social network
      characteristics to the HIV infection risk behavior of frequency of injecting
      heroin and cocaine. The study sample was comprised of 293 inner city injecting
      drug users in Baltimore, Maryland. Most participants (89%) reported at least one
      family member in their social network, and 44% listed their mother or step-mother
      in their network. Presence of family members in personal social networks was not
      related to patterns of drug use examined here; however, those who reported a
      partner in their personal social network injected significantly less often than
      those who did not report a partner. Network density and size of drug subnetworks
      were positively associated with frequency of drug injection. The results of this
      study suggest that social network analysis may be a useful tool for understanding
      the social context of HIV/AIDS risk behaviors.

PMID- 7648993
TI  - Effects of chronic alcohol intake on the vasopressin content in the hypothalamic
      paraventricular and supraoptic nuclei of the mouse. An immunohistochemical and
      morphometric study.
AB  - The present study analyses the response of the paraventricular (PVN) and
      supraoptic (SPO) nuclei of the hypothalamus of the male mouse to chronic alcohol
      intake by immunohistochemical and morphometric methods. We relate the intensity
      of the reaction to A-V with the vasopressin content of the nucleus, as all the
      slides, from the control and experimental groups, were processed at the same time
      and with the same solutions of the antibodies. We suggest that the accumulation
      of vasopressin, observed in the alcohol-treated animals, of both hypothalamic
      nuclei could be related to an inhibition of vasopressin release and/or transport
      from the SPO and PVN to the neurohypophysis and to an increase in vasopressin
      synthesis in the SPO as this nucleus shows an increase in its nuclear sizes, an
      index of the function of the neurons.

PMID- 7648994
TI  - The residual neuropsychological effects of cannabis: the current status of
      research.
AB  - Evidence for the residual neuropsychological effects of cannabis must first be
      separated from evidence regarding (i) the acute effects of the drug, (ii)
      attributes of heavy cannabis users, and (iii) actual psychiatric disorders caused
      or exacerbated by cannabis. The remaining evidence must then be subdivided into
      (a) data supporting a 'drug residue' effect during the 12-24 h period immediately
      after acute intoxication and (b) data suggesting a more lasting toxic effect on
      the central nervous system which persists even after all drug residue has left
      the system. We reviewed the literature, comparing both 'drug-administration'
      studies in which known amounts of cannabis were administered to volunteers, and
      'naturalistic studies' in which heavy marijuana users were tested after some
      period of abstinence. The data support a 'drug residue' effect on attention,
      psychomotor tasks, and short-term memory during the 12-24 h period immediately
      after cannabis use, but evidence is as yet insufficient to support or refute
      either a more prolonged 'drug residue' effect, or a toxic effect on the central
      nervous system that persists even after drug residues have left the body. We
      describe possible study designs to address these latter questions.

PMID- 7648995
TI  - An examination of the cocaine relapse process.
AB  - Although empirical studies of the relapse process have been done with alcoholics,
      smokers, and opiate addicts, comparatively little information is available on the
      relapse process in cocaine abusers. This paper presents data from the Cocaine
      Relapse Interview (CRI), a structured interview that assesses factors associated
      with the onset, course, and termination of cocaine relapse episodes. In a sample
      of 95 cocaine dependent patients, the experiences that occurred with the greatest
      frequency immediately prior to relapse were wanting drugs, being alone, having
      money, and feeling extremely bored and lonely. Following the onset of the
      relapse, the most frequent experience was unpleasant affect, although positive
      reactions were also relatively common. The factors perceived as most important in
      terminating relapse were painful internal states, help-seeking behaviors, and
      other coping responses. Three types of relapse experiences, or pathways, were
      identified: (a) unpleasant affect--painful internal states prior to and
      throughout the relapse; (b) positive affect--positive affect and pleasant social
      experiences prior to relapse coupled with a relatively unproblematic course; and
      (c) sensation seeking--sensation seeking and interpersonal problems prior to
      relapse coupled with mixed emotional reactions and antisocial behavior during the
      relapse, and interpersonal problems at relapse termination.

PMID- 7648996
TI  - Reasons for non-drinking among Israeli adolescents of four religions.
AB  - Adolescent abstainers have largely been ignored in the literature. This article
      describes the reasons for not drinking of 2366 Israeli Jewish, Moslem, Druze and
      Christian adolescents in the north of Israel in the winter of 1994. It analyzes
      the findings by religious group, religiosity (secular versus religious Jews),
      location and gender of Jews, and school grade of Jews and Moslems. Harmful health
      consequences of alcohol use and religious injunction are the most prevalent
      reasons for abstinence among Moslems and Druze. Jews abstain mainly because of
      disliking the taste and/or smell of alcohol and because they 'do not care for
      it'. Christians abstain mainly because of the harmful effects of alcohol on
      health and dislike of its taste and/or smell. The implications of the results for
      prevention are discussed.

PMID- 7648997
TI  - Drug users' spiritual beliefs, locus of control and the disease concept in
      relation to Narcotics Anonymous attendance and six-month outcomes.
AB  - Narcotics Anonymous (NA) is an important support network for drug users emerging
      from abstinence based treatments. However, the views of NA on 'spirituality' and
      the 'disease' nature of addiction could be seen as encouraging an external
      attributional style and have been cited as reasons for non-attendance. After 6
      months ninety percent of 101 drug users in treatment were followed up. Narcotics
      Anonymous attendance was inversely related to drug use for those who had left
      residential care. We found that spiritual beliefs and disease concept beliefs
      were not prerequisites for attendance of NA. Spiritual beliefs were not found to
      cause external attributions for previous drug use or possible future lapse
      events. It emerged that the most powerful predictors of non-attendance were
      positive attitudes to the use of alcohol. Treatment implications are discussed.

PMID- 7648999
TI  - Cumulative index volumes 27-31, 1989-1993.

PMID- 7649000
TI  - Cumulative index volumes 28-32, 1990-1994.

PMID- 7648998
TI  - The DSM-IV field trial for substance use disorders: major results.

PMID- 7649001
TI  - Medicines cheaper over the counter.

PMID- 7649002
TI  - Spatio-temporal dynamics of the primary epileptogenic area in temporal lobe
      epilepsy characterized by neuronal complexity loss.
AB  - Neurons involved in the epileptic processes exhibit high frequency discharges
      scarcely modulated by physiological brain activity. This behaviour should be
      accompanied by a loss of complexity in the corresponding electrographic signal.
      From the theory of non-linear dynamics it is known that the correlation dimension
      allows a quantitative description of complexity in terms of the number of degrees
      of freedom. To test whether a relationship exists between spatio-temporal
      alterations of neuronal complexity and spatial extent and temporal dynamics of
      the epileptogenic area, a moving-window correlation dimension analysis was
      applied to intracranially recorded electrocorticograms of 20 patients with
      unilateral temporal lobe epilepsy. Dimension as a function of time was calculated
      for interictal activity (n = 98) and seizure activity including the pre- and
      postictal phase (n = 28) from recording locations within the epileptogenic area,
      in adjacent areas and in homologous contralateral sites. Pronounced changes of
      the dimension in time were found, gradually decreasing with increasing distance
      from the focal area. Extraction of a single value quantifying the dimension
      variance of interictal activity allowed the primary epileptogenic area to be
      laterized in exact agreement with the results of the presurgical work-up and the
      confirmation of the postoperative outcome, without the necessity of observing
      actual seizure activity.

PMID- 7649003
TI  - Correlation dimension changes accompanying the occurrence of the mismatch
      negativity and the P3 event-related potential component.
AB  - The aim of this study was to apply recently developed mathematical tools of chaos
      theory to the analysis of event-related potentials (ERPs) recorded in paradigms
      in which the mismatch negativity (MMN) and the P3 component appeared. A new
      method, the point correlation dimension (PD2i), was used for data analysis, which
      is more accurate than other algorithms for the calculation of the correlation
      dimension (D2), which latter is a measure of the complexity of the generator(s)
      responsible for producing the analyzed time series, i.e., the EEG. ERPs were
      recorded from Fz, Cz and Pz in 6 subjects. With respect to baseline, the PD2i
      decreased significantly both during the event-related potentials in which the MMN
      and also in which the P3 was present, but the pattern and magnitude of this
      decrease was different between these two situations. The pattern of PD2i changes
      during the occurrence of deviant stimuli eliciting the MMN suggests the presence
      of a frontal MMN generator. The conspicuous PD2i decrease during the occurrence
      of the P3 wave may support the "context closure" hypothesis concerning its
      functional significance.

PMID- 7649004
TI  - Topography of somatosensory evoked magnetic fields following posterior tibial
      nerve stimulation.
AB  - The topography of somatosensory evoked magnetic fields (SEFs) following
      stimulation of the right and left posterior tibial nerves was investigated in 5
      normal subjects (10 nerves). The main deflections N37m-P45m-N60m-P75m and their
      counterparts P37m-N45m-P60m-N75m were identified in the hemisphere contralateral
      to the stimulated nerve. Their equivalent current dipoles (ECDs) were located in
      the foot area of the primary sensory cortex (SI), probably in area 3b. Restricted
      minor deflections, P40m-N40m and N50m-P50m, were considered to be generated in
      area 1 in SI. As the generator sources of P37m-N37m, P40m-N40m and N45m-P45m were
      temporarily changed and interfered with each other, the direction of ECDs
      appeared to be rotated with the passage of time. Small middle-latency
      deflections, N100m-P100m, were clearly identified in 2 subjects. ECDs of these
      deflections were found in the second sensory cortex (SII), in both hemispheres,
      although they were clearer in the hemisphere contralateral to the stimulated
      nerve. In conclusion, short- and middle-latency SEFs are mainly generated in area
      3b in SI contralateral to the stimulated nerve, and responses generated in area 1
      of SI and SII affect the SEFs to some degree, but interindividual differences are
      large compared with SEFs evoked by upper limb stimulation.

PMID- 7649005
TI  - Multiple-generator errors are unavoidable under model misspecification.
AB  - Model misspecification poses a major problem for dipole source localization (DSL)
      because it causes insidious multiple-generator errors (MulGenErrs) to occur in
      the fitted dipole parameters. This paper describes how and why this occurs, based
      upon simple algebraic considerations. MulGenErrs must occur, to some degree, in
      any DSL analysis of real data because there is model misspecification and
      mathematically the equations used for the simultaneously active generators must
      be of a different form than the equations for each generator active alone.

PMID- 7649006
TI  - American EEG Society 1994 annual meeting. Chicago, Illinois, 19-20 September
      1994. Abstracts.

PMID- 7649007
TI  - The significance of the phi rhythm.
AB  - We reviewed two series of patients with the phi rhythm (posterior rhythmic slow
      waves occurring after eye closure) to determine its characteristics and clinical
      significance. Phi rhythm was defined as a minimum of three consecutive
      monomorphic posterior delta waves occurring within 2 sec of eye closure on at
      least two occasions during electroencephalography. Group 1 consisted of 30
      patients (16 male and 14 female) with a mean age of 11.6 +/- 8.4 years (range, 3
      to 46 years) who were evaluated between 1978 and 1993. Phi rhythm most commonly
      occurred when the patient was alert and after concentrated visual attention, such
      as reading or picture or pattern scanning. Seventeen of these patients had
      epilepsy (11 generalized, 3 focal, 1 both, and 2 unclassified). The frequency of
      epilepsy was not significantly different from that of a control group of 60
      patients matched for age and sex; however, generalized epilepsies were more
      common in the phi group (P = 0.008). Group 2 consisted of a previously unreported
      series of 121 patients evaluated between 1960 and 1962. A diverse range of
      underlying clinical diagnoses was evident in both groups. The mechanism of the
      phi rhythm is unknown, but the findings suggest that the origin is subcortical
      and that the presence of this activity should not be considered diagnostic of a
      seizure disorder.

PMID- 7649008
TI  - EEG in successful aging; a 5 year follow-up study from the eighth to ninth decade
      of life.
AB  - Fifteen out of 25 successfully aged individuals completed a 5 year EEG follow-up
      study from the eighth to ninth decade of life with comprehensive
      neuropsychological investigation. One subject suffered from stroke and one
      developed symptoms of dementia during the follow-up. Of 13 subjects who completed
      the follow-up as being healthy, MRI showed subtle enlargement of ventricles or
      subarachnoid spaces and mild signal hyperintensities in a few regions in 2
      subjects. General cognitive decline was not observed (WAIS-R IQ: 113.4 at entry,
      114.3 five years later). There were no EEG dominant frequencies below 8 c-sec and
      no more background slowing than a few theta waves per 10 sec, either at entry or
      5 years later. Intermittent slowing was observed in 9 subjects at entry and in 8
      subjects 5 years later. The prevalence of intermittent slowing was suggested to
      increase with advancing age when compared to previous studies with younger
      elderly. However, intermittent slowing occurred only a few times in an EEG test
      and lasted for less than 2 sec. Moreover, the presence of intermittent slowing
      did not correlate with any neuropsychological decline or any MRI change. This
      type of intermittent slowing was regarded as non-specific and clinically silent.

PMID- 7649009
TI  - Parameters of EEG dimensional complexity in Alzheimer's disease.
AB  - The dimensional complexity or fractal dimension of the EEG recorded at 17
      locations from the 10-20 system was studied using a very fast new algorithm. The
      paper contains 2 parts. First, the influence of several parameters (embedding
      dimension, delay time, high and low frequency cutoff, ADC precision and sweep
      length) on the estimation of dimensional complexity is investigated. Then it is
      shown that patients with Alzheimer's disease (n = 50) have significantly lower
      dimensional complexity than age-approximated non-demented controls (n = 42).

PMID- 7649010
TI  - Delta (0.5-1.5 Hz) and sigma (11.5-15.5 Hz) EEG power dynamics throughout quiet
      sleep in infants.
AB  - Twenty-eight healthy infants, split into 3 groups according to age (group 1: 2-6
      weeks, n = 10; group 2: 7-14 weeks, n = 10; and group 3: 4-12 months, n = 8),
      were recorded during the whole night. For each infant, the longest quiet sleep
      (QS) phase occurring between 8 p.m. and midnight was selected for EEG power
      spectral analysis. The power in the frequency band related to low-frequency delta
      waves (0.5-1.5 Hz, "delta band") and the power in the frequency band related to
      sigma spindles (11.5-15.5 Hz, "sigma band") were analyzed. Group 1 infants showed
      no significant modification of the power in the sigma band in the course of the
      QS phase; the power in the delta band showed a significant increase between the
      second and the third 5 min segment and a decrease thereafter. Group 2 infants
      showed a progressive reduction of the power in the sigma band, whereas the power
      in the delta band increased during the first 15 min. In group 3 infants, the
      sigma band power significantly decreased between the third and the fifth 5 min
      segment without further changes. The power in the delta band, on the contrary,
      increased progressively for the first 20 min and showed a second progressive
      increase beyond 35 min. For both group 2 and group 3 infants, it appeared that
      the change in delta power preceded the change in sigma power. The above results
      provide quantitative evidence that a well-defined temporal inhomogeneity pattern
      in the EEG of the QS phase may appear between 7 and 14 weeks of age and continues
      from the fourth month on.

PMID- 7649011
TI  - Effects of alcohol, at two times of day, on EEG-derived indices of physiological
      arousal.
AB  - Effects of alcohol consumption (0.8 ml/kg) on sleep propensity, spectral
      characteristics of the EEG and self-rated activation in 16 young male subjects,
      were investigated during sessions at each of two times of day (08.00 and 16.00).
      Within-session, time-related changes in the pattern of stage-1 sleep occurrence,
      and of spectral power in different EEG bands indicated that, irrespective of time
      of day, physiological arousal increased as estimated blood alcohol concentration
      (BAC) was rising, and decreased as BAC was falling. Subjective activation was
      reduced by alcohol during both phases of the BAC curve. A pattern of reduced
      stage-1 sleep occurrence, higher absolute high alpha power and higher ratings of
      activation suggested that, irrespective of alcohol condition, physiological and
      subjective arousal was higher during sessions starting at 16.00 than during those
      starting at 08.00. There were no significant interactions between alcohol and
      time of day in respect of any dependent variable. However, the degree to which
      effects reflecting circadian variation may have been masked by effects of limited
      sleep restriction prior to morning sessions remains unclear. Subjects reported
      having slept on only 23.5% of occasions when sleep was scored. Comparison of
      patterns of statistically significant changes in absolute and relative power in
      different bands indicated that the two indices do not provide exactly equivalent
      information about changes in the EEG.

PMID- 7649012
TI  - The component structure of the N1 wave of the human auditory evoked potential.

PMID- 7649013
TI  - On the neural generators of the P300: evidence from temporal lobectomy patients.

PMID- 7649014
TI  - Contributions of anterior and posterior association cortex to the human
      somatosensory P3.

PMID- 7649015
TI  - Are neurotransmitter systems of subcortical origin relevant to the electrogenesis
      of cortical ERPs?

PMID- 7649016
TI  - Cholinergic, serotonergic, and GABAergic effects on the ERP.

PMID- 7649017
TI  - Cholinergic transmission and electrophysiological investigation of the human
      visual system.

PMID- 7649018
TI  - Cognitive event-related potentials in human and non-human primates: implications
      for the PCP/NMDA model of schizophrenia.

PMID- 7649019
TI  - Mismatch negativity to change in complex spectrotemporal sound pattern: a new way
      to study neural learning in the human brain.

PMID- 7649020
TI  - The effects of auditory backward masking on event-related brain potentials.

PMID- 7649021
TI  - Is the pre-attentive comparison of auditory stimuli effected on the basis of
      feature or gestalt representations?

PMID- 7649022
TI  - Are memory traces for simple and complex sounds located in different regions of
      auditory cortex? Recent MEG studies.

PMID- 7649023
TI  - Mismatch field to minor pitch changes in single and paired tones: neuromagnetic
      source localization from derived fields.

PMID- 7649024
TI  - Sensory memory and its role in information processing.

PMID- 7649025
TI  - Mismatch negativity to speech stimuli in school-age children.

PMID- 7649026
TI  - Reduced mismatch negativity and hyperactivation of N2b in depression.

PMID- 7649027
TI  - Consciousness.
AB  - Consciousness offers a major challenge to the neurosciences. Even though
      consciousness is by definition subjective and private to the organism concerned,
      we consider it to be an intrinsic feature of biological processes in the brain.
      As such, it should be viewed in the Darwinian perspective of natural selection
      which implies that the conscious brain function does have survival value and
      cannot be a mere epiphenomenon. We attempted a neurophysiological approach by
      assessing perceptual processing of simple somatic sensory inputs in humans. We
      found that short-latency cortical potentials evoked by a target finger stimulus
      attended by the subject are strongly enhanced, thus manifesting a remarkable
      potentiation of the cognitive representations in primary parietal cortex. About
      80 msec later, the dorsolateral prefrontal cortex discloses enhanced
      electrogeneses which we believe to reflect activation of somatic representations
      in 'working memory'. A functional 'binding' between these critical areas has been
      revealed by the transient and selective synchrony of 40 Hz oscillations recorded
      in the cortical areas of the parietal and prefrontal cortices. We consider these
      re-entrant interactions at 40 Hz to be an essential part of the conscious brain
      mechanisms that achieve the identification of an object (in this example, a
      finger) and the decision to release a motor behavioral response.

PMID- 7649028
TI  - Input modulation in readiness.

PMID- 7649029
TI  - Attentional processes in discriminating visual features and the conjunction of
      features: ERP results.

PMID- 7649030
TI  - Similarities and differences in comprehension processes during reading and
      listening.

PMID- 7649031
TI  - What makes a category a category? ERP correlates of stimulus-to-category
      assignments.

PMID- 7649033
TI  - Partially processed stimulus information as a source of covert and overt errors.

PMID- 7649034
TI  - Analysis of mental workload with ERP indicators of processing stages.

PMID- 7649035
TI  - Event-related potential correlates of errors in reaction tasks.

PMID- 7649032
TI  - A brain potential manifestation of error-related processing.

PMID- 7649036
TI  - Assessment of mental effort by means of slow brain potentials.

PMID- 7649037
TI  - EPIC X: past, present, future.

PMID- 7649038
TI  - DC shifts and cognitive load.

PMID- 7649039
TI  - A model system for the study of attention and the cerebellum: infantile autism.

PMID- 7649040
TI  - Selective listening at fast stimulus rates: so much to hear, so little time.

PMID- 7649041
TI  - ERP signs of distractibility and selectivity in children.

PMID- 7649042
TI  - ERP changes with intelligence and development in children.

PMID- 7649043
TI  - Event related brain potentials and transitions in the level of cognitive
      development during childhood.

PMID- 7649044
TI  - Age-related decline in visual selective attention functioning: evidence derived
      from ERP paradigms.

PMID- 7649045
TI  - EEG and ERPs in young and elderly subjects.

PMID- 7649046
TI  - P300 and neuropsychological function in normal aging and dementia.

PMID- 7649047
TI  - Subjects at risk for psychopathology from the New York High Risk Project: ERPs
      during adolescence and clinical outcomes in young adulthood.

PMID- 7649048
TI  - Conjoint left asymmetry of auditory P300 voltage and MRI volume of posterior
      superior temporal gyrus in schizophrenia: a quantitative evaluation.

PMID- 7649049
TI  - ERPs in adult migraineurs.

PMID- 7649050
TI  - Event-related potentials in migraine: realizations and prospects.

PMID- 7649051
TI  - Methodological considerations related to ERPs in migraine, differences in
      pathophysiology or central processes?

PMID- 7649052
TI  - On the relation between exogenous and endogenous ERP component activity: evidence
      from patients with a subcortical dementia.

PMID- 7649053
TI  - Connections between studies of the neurobiology of attention, psychotic processes
      and event-related potentials.

PMID- 7649054
TI  - Chaotic brain activity.

PMID- 7649055
TI  - Chaos and order in the human brain.

PMID- 7649056
TI  - Localization of ERP generators and identification of underlying neural processes.

PMID- 7649057
TI  - Integration of electrophysiological source analyses, MRI and animal models in the
      study of visual processing and attention.

PMID- 7649058
TI  - The middle latency response generating system.
AB  - In summary, primary pathways are specifically auditory-sensitive, show fine
      frequency tuning, and good time-locking. The responses are reliable and show
      substantial binaural interactions. The primary pathway includes the ventral
      portion of the medial geniculate and the primary auditory cortex. The animal MLR
      recorded from over the temporal lobe, the temporal response, has been associated
      with the primary pathway because it is affected by pharmacological inactivation
      of MGv and electrolytic lesions of the primary auditory cortex. It is a large,
      reliable, rate-sensitive response, that shows a relatively late development and
      high degree of binaural interaction. Non-primary pathways are multimodal, broadly
      tuned, and show only mild binaural interaction. The midline response is
      associated with the non-primary areas because it is affected by pharmacologic
      inactivation of MGcm and mRF, but is not affected by inactivation of MGv or
      lesions of auditory cortex. The midline response is relatively small, labile, and
      rate-resistant. It develops early and shows only a small degree of binaural
      interaction. The generation of MLR thus appears to reflect an interplay of
      primary and non-primary areas in the auditory thalamo-cortical pathway. The non
      primary and primary components may be differentiated in numerous ways: by
      lesions, by stimulus variations, and topographically. The non-primary components
      appear to develop early and are probably sleep state dependent, while the primary
      components develop later and are reliable even in sleep. In young children, it is
      essential to monitor sleep state in order to obtain reliable recordings, leading
      us to speculate that the non-primary components dominate the MLR.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7649059
TI  - The use of multiple Tinel's sign in the identification of patients with
      peripheral neuropathy.
AB  - We have found that the presence of a Tinel's sign is often pervasive in subjects
      with peripheral neuropathy and/or risk factors for developing it. There is a
      paucity of research dealing with the usefulness of Tinel's sign as it relates to
      peripheral neuropathy (PN). The following investigation was carried out to
      determine if multiple Tinel's sign or MTS can be used to identify patients with
      an underlying PN or with risk factors for developing a PN. A total of 102
      subjects were enrolled in the study prospectively. We found MTS to have a
      sensitivity of 79% with a specificity of 42% in detecting peripheral neuropathy
      and a sensitivity of 76% with a specificity of 44% in determining the presence of
      risk factors for developing a peripheral neuropathy. We conclude that MTS can be
      a fairly sensitive indicator of PN or risk factors.

PMID- 7649060
TI  - Neuromuscular adaptations during intensive strength training in middle-aged and
      elderly males and females.
AB  - Effects of progressive heavy resistance strength training combined with explosive
      types of exercises for 12 weeks on electromyographic activity (EMG), muscle cross
      sectional area of the quadriceps femoris (QF), isometric maximal force and force
      time curve of the leg extensor muscles were investigated in 9 middle-aged males
      and 9 females in the 50-year age group (M50; range 44-57), (F50; range 43-54),
      and in 10 elderly males and 11 females in the 70-year age group (M70; range 64
      73), (F70; range 66-73). Great gradual increases took place in maximal force
      during the 12-week training period both in M50 (from 2834 +/- 452 N to 3941 +/-
      772 N; p < 0.001) and in F50 (from 2627 +/- 725 N to 3488 +/- 1017 N; p < 0.001)
      as well as in M70 (from 2591 +/- 736 N to 3075 +/- 845 N; p < 0.01) and in F70
      (from 1816 +/- 427 N to 2483 +/- 408 N; p < 0.001). Significant (p < 0.05-0.001)
      increases occurred also in the maximum integrated EMGs of the trained muscles in
      all groups primarily during the first 8 weeks of the training. Significant (p <
      0.05-0.001) enlargements took place during the 12-week training period in the CSA
      of the QF muscle in all groups. Significant (p < 0.05-0.001) shifts occurred in
      all groups in the shape of the absolute force-time curves and the maximal rate of
      force production increased (p < 0.05-0.001) during the training as well. The
      present findings suggest that progressive heavy strength training combined with
      explosive types of exercises may lead to considerable increases not only in
      maximal strength but also in explosive force production characteristics of the
      trained muscles accompanied by adaptations in the nervous system as well as by
      muscular hypertrophy not only in middle-aged but in elderly males and females as
      well.

PMID- 7649062
TI  - M-wave stability in H-reflex testing: analysis of three rejection criteria.
AB  - Two criteria reported in recent literature were compared with the criterion of
      95% probability (using analysis of variance) for their abilities to detect
      significant differences in M-waves due to repositioning of the ankle joint during
      human soleus H-reflex testing. Data from five normal adult males were analyzed
      using all three rejection criteria, and results from the three analyses were
      compared. Variability of M-wave amplitudes within a condition was found to be
      quite small. Commonly used M-wave rejection criteria which do not account for
      within-condition variability of M-waves were shown to do a relatively poor job of
      detecting alterations of M-wave amplitude due to a change in ankle position.

PMID- 7649061
TI  - A reflex technique to measure presynaptic inhibition in cerebral stroke.
AB  - The purpose of this study was to evaluate the feasibility of reflex excitability
      measurement techniques in the partial measurement of spasticity related to
      cerebral stroke. Techniques involved the testing of the soleus H-reflex at
      specific ankle positions during passive dorsiflexing movements with and without
      background plantarflexing contractions; conditions attempted to simulate the
      terminal stance phase of gait. Testing of 12 stroke subjects, having
      cerebrovascular lesions related only to occlusion of the middle cerebral artery,
      demonstrated significantly (p < 0.01) less inhibition of the H-reflex during
      passive ankle dorsiflexion compared to 12 matched, healthy controls. However,
      evocation of the H-reflex during a low-level, voluntary plantarflexing
      contraction concomitant with passive dorsiflexion, did not reflect a statistical
      difference between the two groups. The two conditions were thought to each
      represent measures of faulty presynaptic inhibition as indicators of cerebral
      spasticity. A Chi-square calculation of sensitivity for the passive ankle
      movement without background plantarflexing contraction condition, was shown to
      significantly differentiate (p < 0.05) between the stroke and normal groups. A
      positive, but weak, correlation was found for stroke subjects between this reflex
      measure and the Ashworth clinical measure of spasticity (r = 0.49). Although
      stroke subjects exhibited increased joint stiffness when the full range of
      passive ankle dorsiflexion movement was considered, in comparison to the matched
      healthy control subjects, no significant increase in passive stiffness was found
      at the joint position of the reflex evocation. Size of the cerebral lesion, as
      determined from CT or MRI scan, was not related to the spasticity measures.
      Therefore, in a homogeneous stroke sample, a component of cerebral spasticity
      i.e., faculty Ia presynaptic inhibition, has been measured during a simulated
      functional movement in the lower extremity and was shown to differentiate this
      group from a matched, healthy, control sample. Joint stiffness did not
      contaminate the measures.

PMID- 7649063
TI  - Sensory nerve conduction studies of the less frequently examined nerves.
AB  - The normal values of latency, amplitude and conduction velocity of the sensory
      nerve action potentials of a group of infrequently or even rarely examined
      nerves, are reported. A number of preliminary testings was made in order to
      establish the most appropriate and practical stimulation and recording procedures
      for the study of the axillary, lateral antebrachial cutaneous, medial
      antebrachial cutaneous, lateral femoral cutaneous, saphenous, superficial
      peroneal and medial plantar nerves. The examination techniques and the normal
      data obtained from their application on 30 healthy subjects, 20 to 36 years of
      age, at constant skin temperature, are discussed and compared to those already
      existing in the available literature.

PMID- 7649064
TI  - The tendon reflexes in the electrodiagnosis of sciatica.
AB  - In order to determine the diagnostic value of the electromyographically tested
      tendon reflexes (ETR) in lumbosacral radiculopathies, we compared the latency and
      amplitude of the knee (EKTR) and Achilles tendon reflex (EATR) to their clinical
      testing and to the EMG and H reflex values in 200 non selected patients (126 men,
      74 women) aged 24-68 years (48.6 +/- 9.4). The control group was composed of 50
      healthy volunteers (28 men, 22 women) aged 25-60 yrs (44 +/- 8.5). The combined
      electrophysiological reflex examination was abnormal in 45% of the affected
      limbs, being the most frequent pathological finding. EMG was abnormal in 34.4%
      and H reflex in 30.4% of the affected limbs. Furthermore, the EATR taken
      separately was more sensitive than the H-reflex (42.8% versus 30.4%).
      Pathological ETR were elicited in a considerable percentage of the clinically
      normal tendon reflexes (TR): 7.3% of the knee and 14.1% of the Achilles TR. On
      the other hand 65% of the clinically absent ATR were recorded electrically
      producing abnormally low and delayed muscle evoked potentials.

PMID- 7649065
TI  - Percutaneous S1 root somatosensory evoked potential.
AB  - Spinal and cortical evoked potentials were recorded in response to percutaneous
      stimulation of the first sacral root which was accessed via the dorsal sacral
      foramen. A very high amplitude spinal response is easily recordable using surface
      electrodes. Cortical responses were inconsistently elicited and had highly
      variable latencies, amplitudes and morphologies.

PMID- 7649066
TI  - Design of a myo-seismic transducer for non-invasive transcutaneous vectorial
      recording of locally fast muscle-fibre micro-contractions.
AB  - Mechanical recording usually concerns the analysis of movements in bio-mechanical
      research projects. Mechanical recording of locally fast muscle-fibre micro
      contractions, however, is a little-developed and rarely-applied myographic
      technique. In the last decade, acoustic or myophonic measurements came
      increasingly into the picture when they were also applied to research on general
      muscle activity, such as in muscle fatigue studies. In this paper, a new micro
      seismic recording technique is introduced. The technique registers extremely
      local activity in the velocity and force vector of skin movement as a function in
      time. The recording method is sensitive to micro excursions caused by muscle
      fibres under the skin. The resolution in time is at least 100 us, which is
      demonstrated in an experiment where a mechanical contraction is provoked by
      electrical stimulation of the median nerve. This indicates a seismic variant,
      refered to as seismic-myography (SMG), of surface EMG's, and offers complementary
      features. The most important features are: 1. Insensitivity to low frequent,
      large movement artefacts. 2. Sensitivity to fast mechanical micro-excursions and
      velocities. 3. Fast and precise discrimination of local mechanical events. 4.
      Vectorial reconstruction of superficial mechanic activity which can be used for
      the identification and functional behaviour of subcutaneous muscle fibres and, in
      addition, for the localisation of motor endplate zones. 5. The method is easy to
      use.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7649067
TI  - [Pharmaco-clinical aspects of methadone. Literature review of its importance in
      treatment of substance dependence].
AB  - In order to assess the initial hypotheses of Dole, who set the objectives of
      methadone maintenance in 1966, this article reviews all research findings
      available in the field. The side-effects of methadone appear rather infrequent
      with few long lasting effects. The selection of a dose sufficiently high to block
      opiat receptors seems make the patient little or not sensitive to heroin intake
      whereas treatment compliance seems to be dose-related until a plateau of about
      120 mg/day. All studies show a dramatic decrease in heroin intake. In contrast, a
      change in the drug use profile toward an increase in alcoholism and cocaine
      intake appears in certain subjects. Regarding AIDS, results seem less clear,
      showing a global decrease in intravenous use as behavior at risk but providing
      apparently not a total protection unless complete discontinuation. The decrease
      in antisocial behavior appears clearly, interpreted as a decrease in the economic
      pressure on the consumer. As a consequence of these results, an assistance in
      social rehabilitation appears more effective. Whereas the literature regarding
      withdrawal clearly shows the usefulness of the technique regarding the duration
      and the persistence of withdrawal symptoms, it remains very blurred regarding
      long-term results. The average age (about 30 years) and the average duration of
      drug abuse (about 10 years) of the patients included in those studies lead to the
      conclusion that only a marginal part of the total population is taken in charge,
      meaning that these techniques will never be solutions to a problem of society but
      only individual therapies. This article also raises the problem of the passionate
      climate associated with these issues--with negative consequences regarding
      objectivity--and the methodological limitations found in too many studies on this
      topic.

PMID- 7649068
TI  - [Psychotherapeutic process in a day hospital: results of a survey and importance
      of qualitative data].
AB  - This survey was carried out in a psychiatric day hospital over three years on all
      patients admitted. The aim was to assess the patients' state at discharge, and to
      identify the factors to explain the clinical changes, in particular to evaluate
      the impact of the various types of therapy proposed. The patients were evaluated
      when they entered the hospital and at discharge using mainly validated translated
      English-language questionnaires ("Health Sickness Rating Scale" of Luborsky,
      "Helping Alliance questionnaire" of Luborsky), but also two instruments developed
      and validated by our team: "Clinical Evaluation Profile", and the "Commitment
      Scale". The results provide not only a good description of the patients' state at
      arrival but also of their evolution. The factors found to be important in the
      evaluation were similar to those identified in most of previous studies, i.e. the
      initial severity, and quality of the therapeutic relationship, but we also found
      that the degree of commitment of the patients to the various therapies offered
      was important. In addition, we found that, when using the commitment scale in
      homogeneous subgroups of patients (identified using the CIM 9 diagnostic scale)
      were examined, the favourable outcome of a given psychotherapeutic approach was
      dependent on the type of the pathology. Thus, patients with personality disorders
      and high scores at the commitment scale benefited above all from group therapy.
      The reverse was found for patients with neurotic disorders. For patients
      suffering from schizophrenia the most important factor was the commitment to the
      background milieu of the hospital. These observations are in contradiction with
      some of the main conclusions (known as the equivalence paradox) from english and
      american studies over the last 40 years of Psychotherapy Research, which state
      that all psychotherapies are equivalent, and that the reason why some give
      successful results, and other do not can, only be by non specific factors (i.e.
      the quality of the therapeutic bond, patients' motivations, etc.). From our
      results, if homogeneous subgroups of patients are considered and if we use
      subjective (commitment to the therapy) instead of hard data (as for example
      having this type of therapy or an other one, or the length of therapy, ect.), we
      can distinguish the effect of the various psychotherapeutic approaches at least
      in a psychiatric institution.

PMID- 7649069
TI  - [Epidemiology of somatoform disorders in the general French population].
AB  - A telephone survey based on 504 interviews, representative of the French
      population over 18, allowed to gauge the annual prevalence and identify the
      characteristics of somatoform disorders. This study was based on the inventory of
      19 symptoms divided into 5 categories: gastrointestinal, pain, dermatological,
      cardiorespiratory and gynaecologic/urinary. "Medical somatoform disorders" (MSD)
      were defined as the repeated occurring, during the previous year, of not less
      than 1 symptom with an evolution duration equal or superior to 6 months, and
      causing personal and familial or professional problems. Such disorders had, in
      addition, to motivate one or more medical consultations concluding to the lack of
      somatic disease. These criteria included those proposed in DSM IV for the
      diagnosis of "Undifferentiated Somatoform Disorder", except for the exclusion
      criteria (E) which was not included in this study. Three out of four subjects
      (76% of the population) declared to endure not less than 1 somatic symptom in the
      course of the previous year. Near 1 out of 5 subjects (19%) had one MSD. MSD were
      more frequent among females than among males (sex-ratio F/M = 1.82). This data
      traces 3 types of phenomena: the somatic disorders prevalence and the
      consultation ratio in case of somatic disorders were higher among females than
      males; conversely, MSD ratio among somatic disorders consultants is higher among
      males than females. MSD prevalence does not vary with age, except for an
      underrepresentation among patients aged over 65 (13%).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7649070
TI  - [Depression and dementia: contribution to the French validation of 2 depression
      scales: the Cornell Scale for Depression in Dementia and the Dementia Mood
      Assessment Scale].
AB  - This study establishes, in a sample of elderly demented patients, the validity of
      a french translation of two depression rating scales: Cornell Scale for
      Depression in Dementia (CSDD, Alexopoulos 1988), Dementia Mood Assessment Scale
      (DMAS, Sunderland 1988). Cognitive performances of 24 patients (mean age 77.9 +/-
      7.4, 7 men 17 women), meeting DSM III-R criteria for dementia, have been
      evaluated. Four clinicians, blind to the clinical diagnosis of depression
      established by a psychogeriatrist, have evaluated the sample with the two scales.
      All patients present middle to severe dementia: MMS = 16.8 +/- 3.45. Eleven
      patients (45%) present moreover depression. Concurrent validity has been
      established against Hamilton Depression Rating Scale, test retest reliability,
      inter-rater reliability and internal consistency are established for each scale.
      These characteristics are pleading for a good reliability of the french
      translation of CSDD and DMAS, in the presence of cognitive impairment.

PMID- 7649071
TI  - [Antiparkinson drugs in neuroleptic treatment: comparative study of progressive
      and abrupt withdrawal].
AB  - The systematic and long term association of anti-parkinsonian drugs to
      neuroleptics is questioned by many authors because of their side effects and
      their toxicomanogenous risks whereas their efficiency in extrapyramidal effects
      of prophylaxis is not certain. This work aims at evaluating the interest of
      prescribing long term parkinsonian drug in association with neuroleptics. The
      study centered on 101 psychotic patients treated with neuroleptics, and followed
      on an ambulatory bases. 97% of this patients systematically received
      antiparkinsonian drugs. Extrapyramidal symptoms of varied intensity have noted
      for 61% of patients. The authors have compared, in double blind, the effects of
      the progressive and abrupt withdrawal of anti-parkinsonian drugs for 37 patients
      among the 101. These patients have been regularly treated for at least 6 months
      by neuroleptics (fluphenazine or pipothiazine) in association with
      trihexyphenidyle. They were randomly divided into 3 groups, and statified by sex
      and type of neuroleptic. For group I, composed of 13 patients, trihexyphenidyle
      is abruptly withdrawn and replaced by a placebo. For group II, composed of 11
      patients, withdrawal is progressive for 2 weeks, trihexyphenidyle being replaced
      by a placebo. Group III, composed of 13 patients, is a sample group which went on
      receiving trihexyphenidyle. The results of this study showed that within the
      brutal withdrawal group (group I), 10 patients over 13 needed trihexyphenidyle
      again, whereas only 3 patients over 11 needed it in the progressive withdrawal
      group (group II). In the sample group (group III), one patient over 13 showed
      extrapyramidal symptoms, necessitating his leaving school. The global chi 2 is
      significant with p < 0.001.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7649072
TI  - [Major agitated-anxious versus blunted-retarded depression: differential effects
      of fluoxetine].
AB  - A multi-centre study was designed to evaluate the efficacy and tolerance of
      fluoxetine in two groups of major depression: "agitated-anxious" and "blunted
      retarded". The study included 50 patients presenting a major depressive episode
      (following DSM III-R criteria and score > or = 20 on MADRS): 26 in "agitated
      anxious" group (score > or = 15 on Hamilton anxiety scale and > or = 10 on Tyrer
      anxiety brief scale) and 24 in the "blunted-retarded" group (score > or = 15 on
      Widlocher retardation scale and > or = 10 on Abrams-Taylor blunted affect scale).
      After one week period on placebo, all patients were treated in an open design
      with fluoxetine at a fixed daily dose of 20 mg and followed on a period of 6
      weeks with active treatment. In spite of a significant antidepressant efficacy of
      fluoxetine in the two groups, better results were observed in the "agitated
      anxious" depressed group: marked improvement on MADRS total score at day 42 (76%
      decrease vs 62% in the "blunted-retarded" group, p = 0.012), greater number of
      "responders" defined by a decrease > or = 50% on MADRS total score and a total
      score < or = 12 (95% vs 63%, p = 0.04), better patient's global impression on
      efficacy (54% of "excellent efficacy" vs 18%, p = 0.012), more improvement on
      HSCL-58 total score (mean decrease of 69% vs 39%, p = 0.016), higher improvement
      on "hostility/interpersonal hypersensitivity" score (mean decrease of 74% vs 37%,
      p = 0.001) and on "anger attacks/irritability" sub-score (mean decrease of 73% vs
      30%, p = 0.0002).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7649073
TI  - [Group memory therapy in neurologic amnesia].
AB  - The aim of our approach was to improve the memory of head injured memory impaired
      people without associated intellectual deterioration. Subjects participated in
      group each weekday during ten weeks. The aim of strategies was to help the
      patient of recovery learning strategies. Exercises can be repeated to produce the
      use of learning strategies in the real life. 19 patients (11 subjects with a
      traumatic brain injury and 8 subjects with a cerebral vascular accident)
      completed the treatment are measured before and after the rehabilitation. In a
      clinic study our memory therapy was more satisfactory on visual memory than
      verbal memory on a French standardised memory test (the Signoret memory battery).
      But there is no change in the evaluation of everyday memory measured with the AMQ
      of Van Der Linden. The comparison of the two sub groups has given to show which
      pathology will benefit the more the method. These first findings suggested that
      it was useful to reinforce everyday memory and to include the family members
      more. It will also be interesting to modify the program for the reeducation of
      the verbal memory. A control study was necessary to evaluate the validity of our
      approach.

PMID- 7649074
TI  - The somatostatin receptor--a window of therapeutic opportunity?

PMID- 7649075
TI  - Internalization of the radioiodinated somatostatin analog [125I-Tyr3]octreotide
      by mouse and human pituitary tumor cells: increase by unlabeled octreotide.
AB  - Recently, we developed a technique that allows the in vivo visualization in man
      of somatostatin receptor-positive neuroendocrine tumors after i.v. injection of
      [125I-Tyr3]octreotide or [111In-DTPA-D-Phe1]octreotide. Radiotherapy of such
      tumors using somatostatin analogs coupled to alpha- or beta-emitting
      radionuclides has been proposed as an application for radiolabeled somatostatin
      analogs. To develop this concept further, it is of importance to know whether the
      above-mentioned radiolabeled somatostatin analogs are internalized by the tumor
      cells, and whether it might be possible to manipulate the degree of
      internalization. In the present study we investigated the internalization of a
      stable somatostatin analog, [125I-Tyr3]octreotide, by mouse AtT20/D16V pituitary
      tumor cells and primary cultures of human GH-secreting pituitary tumor cells.
      Treatment of the cells with low pH was used to distinguish between membrane-bound
      (acid-releasable) and internalize (acid-resistant) radioligand. [125I
      Tyr3]octreotide showed a time-dependent increasing accumulation in AtT20 cells;
      after 4 h of incubation, values up to 6-8% of the dose of radioligand added were
      obtained. Binding and internalization of [125I-Tyr3]octreotide were temperature
      dependent and inhibited by pertussis toxin. Inhibitors of lysosomal degradation
      did not increase the amount of internalized radioligand. After 4 h of incubation,
      88% of the radioactivity present in the cells was still peptide bound, suggesting
      a low intracellular breakdown of this radioligand. Six of seven human GH
      secreting adenoma cell cultures also internalized [125I-Tyr3]octreotide
      (variation between 0.24-4.98% of the dose radioligand added). Displacement of
      binding and internalization of [125I-Tyr3]octreotide by unlabeled octreotide
      showed a bell-shaped curve in AtT20 cells. At low concentrations (0.1 and 1 nM),
      binding and internalization were increased, whereas at higher concentrations,
      saturation occurred. In contrast to this, binding of [125I-Tyr3]octreotide to a
      broken cell preparation of AtT20 cells was displaced in a dose-dependent manner
      by unlabeled octreotide, with an IC50 of 0.1 nM. Similar observations were made
      in the human GH-secreting adenoma cell cultures. In conclusion, a high amount of
      [125I-Tyr3]octreotide is internalized in a specific-, time-, temperature-, and
      pertussis toxin-sensitive GTP-binding protein-dependent manner by mouse AtT20 and
      human GH-secreting pituitary tumor cells. In the presence of a low concentration
      of unlabeled octreotide, a rapid increase in the amount of [125I-Tyr3]octreotide
      internalized by AtT20 cells and by the majority of the human GH-secreting adenoma
      cell cultures was found.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7649076
TI  - Glucocorticoid receptor expression is down-regulated by Lp(a) lipoprotein in
      vascular smooth muscle cells.
AB  - Glucocorticoids have been reported to protect against atherosclerosis and have
      been used clinically as protective therapy for restenosis after balloon
      angioplasty. Recently, Lp(a) lipoprotein [Lp(a)] levels have been suggested to be
      an independent risk factor for atherosclerosis, although its mechanisms of action
      are still uncertain. To clarify this atherogenic mechanism of Lp(a), we
      investigated the effects of Lp(a) on glucocorticoid receptor (GR) expression in
      human vascular smooth muscle cells (SMC). Levels of nuclear GR in SMC began to
      decrease after 12-h incubation with Lp(a), to 55 +/- 8% of the control value at
      48 h; binding affinity did not change. Lp(a) had no effect on estrogen receptor
      binding in SMC. Moreover, low, very low, and high density lipoproteins had no
      effect on GR binding in SMC. The effects of Lp(a) on nuclear GR in rat SMC were
      very similar to those in human SMC; in contrast, Lp(a) did not alter GR or
      estrogen receptor levels in rat endothelial cells. GR messenger RNA levels in SMC
      decreased after 1-h treatment with Lp(a) to 23% of the control value after 12 h.
      Further, the antiproliferative effect of glucocorticoids on SMC was blunted by
      exposure to Lp(a). We conclude that Lp(a) down-regulates GR gene expression,
      resulting in a decreased number of GR in SMC. These findings suggest the
      possibility of a novel atherogenic mechanism of Lp(a) via inhibition of a
      protective action of glucocorticoids on SMC.

PMID- 7649077
TI  - Evidence that somatotroph differentiation during chicken embryonic development is
      stimulated by a blood-borne signal.
AB  - We reported previously that GH-secreting cells differentiate by day 16 of chicken
      embryonic development. In the present study, primary cultures of anterior
      pituitary cells from 10-, 12-, 14-, and 16-day-old chicken embryos were incubated
      for 2 or 6 days in serum-free medium or medium supplemented with serum from day
      12 or day 16 embryos (1% serum by volume). After this culture period, the
      pituitary cells were recovered and subjected to reverse hemolytic plaque assays
      for chicken GH. GH-secreting cells did not differentiate spontaneously in serum
      free cultures derived from any of the embryonic ages tested, indicating that
      differentiation of somatotrophs does not occur based only on the relative age of
      the presumptive GH cell. However, we found that treatment for as little as 2 days
      with serum from day 16 (but not day 12) embryos stimulated somatotroph
      differentiation in cultures derived from day 12, 14, and 16 embryos. These
      results indicate that an activity capable of stimulating GH cell differentiation
      in vitro is present in day 16 embryonic serum and that the presumptive GH cells
      were responsive to the somatotroph-differentiating effects of day 16 embryonic
      serum as early as day 12 of development. Next, serum from day 12, 14, and 16
      embryos was evaluated over a 25-fold-range in concentration (0.2-5.0% by volume)
      using pituitary cells from day 12 embryos as an in vitro bioassay. Treatment with
      day 12 serum at any of the concentrations tested had no significant effect (P >
      0.05), relative to that in serum-free cultures, in which 0.8 +/- 0.4% of all
      pituitary cells released GH. In contrast, treatment with day 14 and day 16 serum
      increased the percentage of cells that released GH to 8.0 +/- 1.3% and 12.0 +/-
      0.8%, respectively (1% serum by volume). Thus, the level of somatotroph
      differentiating activity in embryonic serum was undetectable in day 12 embryos,
      intermediate in day 14 embryos, and increased to high levels by day 16 of
      development concomitant with the appearance of GH-secreting cells in vivo
      reported previously. Next, the specificity of this response to day 16 serum was
      tested further by treating day 12 cells with peptides known to stimulate GH
      release in adult animals, GH-releasing hormone and TRH, and a GH-releasing
      hormone-related peptide (vasoactive intestinal peptide). None of these peptides
      was found to stimulate somatotroph differentiation at the doses tested (10-9 and
      10-7 M).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7649078
TI  - Cloning, expression, and tissue distribution of the rat nicotinamide adenine
      dinucleotide-dependent 11 beta-hydroxysteroid dehydrogenase.
AB  - A pcDNAI adult rat kidney complementary DNA (cDNA) library was screened using a
      sheep 11-hydroxysteroid dehydrogenase 2 (11 beta HSD-2) probe, and the isolated
      clones were sequenced. The 5'-end of the cDNA was determined by 5'-rapid
      amplification of cDNA ends. The rat 11 beta HSD-2 cDNA is 1864 base pair (bp)
      long. It consists of a 5'-untranslated region of 126 bp, an open reading frame of
      1203 bp, and a 3'-untranslated region of 535 bp. The predicted protein contains
      400 amino acid residues, with a calculated mol wt of 43,700. The rat 11 beta HSD
      2 protein sequence is 85% homologous to human 11 beta HSD-2 and 76% to sheep 11
      beta HSD-2. Expression of 11 beta HSD-2 messenger RNA by Northern blot and
      reverse transcription-polymerase chain reaction was high in kidney, distal colon,
      and adrenal and lower in the lung, hypothalamus, hippocampus, and midbrain. The
      rat 11 beta HSD-2 was transiently transfected into modified Chinese hamster ovary
      cells. Cells transfected with the 11 beta HSD-2 cDNA converted corticosterone
      into 11-dehydrocorticosterone. Conversion of corticosterone to 11
      dehydrocorticosterone was NAD+ dependent and had a Km of 10.1 +/- 2.1 nM. In
      conclusion, we have cloned a rat NAD(+)-dependent 11 beta HSD with tissue
      distribution and kinetic characteristics suggesting that it could play a
      significant role in mineralocorticoid receptor selectivity.

PMID- 7649079
TI  - Structure-function relationship of human parathyroid hormone in the regulation of
      vitamin D receptor expression in osteoblast-like cells (ROS 17/2.8).
AB  - Studies of the relationship between PTH structure and function in the activation
      of protein kinases have revealed that different regions within the biologically
      active PTH-(1-34) peptide are responsible for different functions. The first two
      N-terminal amino acids are required for plasma membrane adenylyl cyclase
      stimulation, and the C-terminal region 29-32 is necessary for the translocating
      activity of protein kinase C. In the present study, we explored the structure
      function relationship of human (h) PTH in the regulation of the vitamin D
      receptor (VDR) in osteoblast-like cells (ROS 17/2.8). VDR-rich cytosol extract
      was prepared after the confluent cells were incubated with different hPTH
      fragments for 16 h. hPTH-(1-34) at concentrations of 10(-9)-10(-7) M caused a
      dose-dependent decrease in VDR content from a control level of 70.2 +/- 2.2
      fmol/mg protein to 62.1 +/- 3.3 (-16%) at 10(-9) M, 52.3 +/- 5.3 (-25.5%; P <
      0.02) at 10(-8) M, and 45.5 +/- 3.5 fmol/mg protein (-35.3%; P = 0.001) at 10(-7)
      M (n = 6). hPTH-(1-31) also decreased VDR content from 65.5 +/- 3.6 to 55.2 +/-
      7.9 (-19.5%) at 10(-9) M, 44.3 +/- 5.8 (-32.4%; P < 0.05) at 10(-8) M, and 40.6
      +/- 3.2 fmol/mg protein (-38.9%; P < 0.05) at 10(-7) M (n = 6). Incubation of ROS
      17/2.8 cells with 0.5 nM 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] led to up
      regulation of VDR content by 340-370% of the control value. hPTH-(1-34) decreased
      the VDR up-regulatory effect of 1,25-(OH)2D3 from 340% to 230% of the control
      value at 10(-8) M (P < 0.0001) and 170% of the control value (P < 0.0001) at 10(
      7) M, respectively (n = 6). hPTH-(1-31) also decreased the receptor up-regulatory
      effect of 1,25-(OH)2D3 from 370% to 286% (P < 0.02) at 10(-8) M and 220% (P <
      0.002) at 10(-7) M, respectively (n = 6). hPTH-(3-34) and -(13-34) at
      concentrations of 10(-9)-10(-7) M did not decrease VDR content in either the
      absence or presence of 1,25-(OH)2D3. Quantitation of VDR messenger RNA by reverse
      transcription-polymerase chain reaction showed that PTH-(1-34) and -(1-31) at 10(
      7) M, but not PTH-(3-34) and -(13-34), inhibited ROS 17/2.8 cell VDR gene
      expression in both the absence and presence of 1,25-(OH)2D3.(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 7649080
TI  - Stress increases brain-derived neurotropic factor messenger ribonucleic acid in
      the hypothalamus and pituitary.
AB  - Brain-derived neurotropic factor (BDNF) is a member of the nerve growth factor
      family that is important for neuronal survival and plasticity. We recently
      demonstrated that stress decreases BDNF messenger RNA (mRNA) levels in the
      hippocampus, which raises the possibility that BDNF may play a role in regulation
      of the hypothalamic-pituitary-adrenal axis. The purpose of this study was to
      determine whether BDNF expression is present and influenced by stress in other
      brain areas relevant to control of the hypothalamic-pituitary-adrenal axis. Using
      in situ hybridization, we found that BDNF mRNA is present in the parvocellular
      portion of the hypothalamic paraventricular nucleus (PVN), the lateral
      hypothalamus, and the anterior and neurointermediate lobes of the pituitary in
      rats. Acute (2-h) or repeated immobilization stress increased BDNF mRNA in all of
      these areas. This was in distinct contrast to stress-induced decreases in
      extrahypothalamic areas, including the basolateral amygdala, claustrum, and
      cingulate cortex as well as the hippocampus. BDNF was expressed in both CRF and
      TRH neurons in the PVN. Reducing glucocorticoid or thyroid negative feedback
      increased BDNF mRNA in the PVN and anterior pituitary, but not in the
      neurointermediate lobe. These results suggest that BDNF is a stress-responsive
      intercellular messenger that may be an important component of the stress
      response.

PMID- 7649081
TI  - Parathyroid hormone (PTH)/PTH-related protein receptor messenger ribonucleic acid
      expression and PTH response in a rat model of secondary hyperparathyroidism
      associated with vitamin D deficiency.
AB  - The aim of the present work was to characterize at the molecular level the
      mechanism of PTH resistance in a rat model of secondary hyperparathyroidism
      resulting from vitamin D deprivation. PTH/PTH-related protein (PTHrp) receptor
      messenger RNA (mRNA) expression, assayed by ribonuclease protection analysis, was
      studied in the kidney, femoral epi/metaphysis, and diaphysis. In addition, in the
      kidney, PTH/PTHrp receptor mRNA expression was correlated to receptor function by
      measuring adenyl cyclase activity in crude renal membranes after stimulation by
      PTH (10(-10) - 10(-6) M), forskolin (0.1 and 0.2 mM), NaF (5 and 10 mM), and
      isoproterenol (1 and 10 microM). Four groups of rats were studied to investigate
      the effects of calcium, PTH, and/or vitamin D status. The first group received a
      control diet (D+D+). The second group received a diet deficient in vitamin D
      until death (D-D-). In the two other groups that also received a vitamin D
      deficient diet, the hypocalcemia and the hyperparathyroidism were later
      corrected, by either vitamin D supplementation (D-D+) or lactose and high calcium
      diet (D-Ca+), 1 week before death. The results revealed a 2-fold decrease in the
      PTH-induced adenyl cyclase activity of the renal membranes in the D-D- rats
      compared to those in the three other groups. There was no significant difference
      in the four groups in adenyl cyclase activity stimulated by forskolin, NaF, and
      isoproterenol. The decrease in PTH-induced adenyl cyclase activity was associated
      with an approximately 2-fold increase in PTH/PTHrp receptor mRNA expression in
      the kidneys of the D-D- rats compared to controls. Normalization of PTH/PTHrp
      receptor mRNA expression was observed after vitamin D supplementation (D-D+
      rats), but not after correction of the hypocalcemia and secondary
      hyperparathyroidism by oral lactose and calcium supplementation. In the
      epi/metaphysis, an approximately 2-fold increase in PTH/PTHrp receptor mRNA was
      also observed in the D-D- rats compared to the controls; this increase was
      partially corrected upon normalization of the calcemia and PTH levels with either
      vitamin D (D-D+ group) or lactose/calcium (D-Ca+ group). In the diaphysis, no
      change in the expression of PTH/PTHrp receptor mRNA was observed in any
      group.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7649082
TI  - Insulin-like growth factors (IGFs) stimulate the release of alpha 1
      antichymotrypsin and soluble IGF-II/mannose 6-phosphate receptor from MCF7 breast
      cancer cells.
AB  - The growth of hormone-responsive MCF7 human breast cancer cells is controlled by
      steroid hormones and growth factors. By metabolic labeling of cells grown in
      steroid- and growth factor-stripped serum conditions, we show that insulin-like
      growth factors (IGF-I and IGF-II) increase by approximately 5-fold the release of
      several proteins including cathepsin D, alpha 1-antichymotrypsin, and soluble
      forms of the multifunctional IGF-II/mannose 6-phosphate (M6P) receptor. Two
      soluble forms of IGF-II/M6P receptors were detected, one major (approximately 260
      kilodaltons) and one minor (approximately 85 kilodaltons) that probably
      represents a proteolytic fragment of the larger soluble molecule. IGFs increased
      receptor release in a dose-dependent fashion with 50-60% of newly synthesized
      receptor released at 5-10 nM IGFs. The release of IGF-II/M6P receptors correlated
      with the levels of secreted cathepsin D in different human breast cancer cells or
      in rats stable transfectants that are constitutively expressing variable levels
      of human cathepsin D. IGFs had a stronger effect on IGF-II/M6P receptor release,
      whereas estradiol treatment preferentially enhanced the release of protease and
      antiprotease. We thus demonstrate that in human breast cancer cells, IGFs not
      only act as strong mitogens but also regulate release of alpha 1
      antichymotrypsin, IGF-II/M6P-soluble receptor, and cathepsin D; three proteins
      that potentially regulate cell proliferation and/or invasion.

PMID- 7649083
TI  - Growth hormone specifically stimulates the expression of low density lipoprotein
      receptors in human hepatoma cells.
AB  - Human GH (hGH) has been shown to stimulate hepatic low density lipoprotein (LDL)
      receptor expression in man in vivo. To further characterize this effect in vitro,
      we determined the expression of LDL receptors in cultured human hepatoma (HepG2)
      cells exposed to hGH. After incubation with hGH, stimulation of LDL receptors
      appeared at a concentration of 0.25 nM hGH. The presence of hGH receptors on
      HepG2 cells could be demonstrated by immunocytochemistry using a hGH receptor
      specific monoclonal antibody. Binding studies, using 125I-labeled hGH, revealed
      high affinity binding with the appropriate somatogenic specificity. The LDL
      receptor induction was specific for hGH, as both bovine GH and recombinant human
      PRL were without effect. The LDL receptor stimulation occurred in parallel with
      increased levels of LDL receptor messenger RNA. Inclusion of dexamethasone and
      thyroid hormone in the incubation medium enhanced the LDL receptor stimulation by
      hGH. Although incubation with insulin-like growth factor-I (IGF-I) stimulated LDL
      receptor expression, the hGH-induced stimulation was unaltered after
      preincubation of cells with a monoclonal mouse anti-IGF-I antibody, suggesting
      that the release of IGF-I is not involved in LDL receptor stimulation by hGH. We
      conclude that hGH specifically induces the LDL receptor in cultured HepG2 cells
      at both the protein and the messenger RNA level, and that the induction is
      independent of IGF-I release.

PMID- 7649084
TI  - Cloning of a teleost fish glucocorticoid receptor shows that it contains a
      deoxyribonucleic acid-binding domain different from that of mammals.
AB  - In the teleost fish, physiological and biochemical studies suggest that
      glucocorticoids regulate both salt balance and metabolic activities. In mammals,
      however, these functions are divided between glucocorticoids and
      mineralocorticoids. In mammals, separate receptors for these two classes of
      steroid hormone have been cloned and sequenced. To begin to understand the
      regulation in fish of the vital processes ascribed to glucocorticoids, we have
      cloned, sequenced, expressed, and studied the steroid-binding and transcriptional
      activation capabilities of the rainbow trout (Onchorhynchus mykiss)
      glucocorticoid receptor. Northern blot analysis shows a single rainbow trout GR
      messenger RNA species of 7.5 kilobases expressed in gill, intestine, skeletal
      muscle, kidney, and liver. The trout GR 2274-nucleotide coding sequence provides
      for a protein of 758 amino acids, with appropriate similarities to mammalian GR,
      with one striking exception. As in other members of the steroid/thyroid/retinoid
      receptor family, the DNA-binding domain contains two putative zinc fingers. These
      have high homology with those of other GRs. However, between the zinc fingers in
      the trout GR are found 9 more amino acids than are seen in mammalian GRs, raising
      questions as to the functional form of the fish, as opposed to the mammalian, GR.
      It has been proposed that as fish appear to use glucocorticoids for both
      metabolic and salt control, presumably through a single GR, GR would prove to be
      the evolutionary precursor to mammalian GR and mineralocorticoid receptor (MR).
      Computer analysis of the known sequences of GRs and MRs, however, suggests that
      the fish GR did not give rise to the MR of higher animals, but that both
      subfamilies of receptor arose from some earlier gene.

PMID- 7649085
TI  - Ca2+/calmodulin-dependent protein kinase II and synapsin I-like protein in mouse
      insulinoma MIN6 cells.
AB  - Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) may play a key role
      in the regulation of insulin secretion. We obtained evidence for the presence of
      CaM kinase II and its substrate, a 84-kilodalton (kDa) protein, in mouse
      insulinoma MIN6 cells. CaM kinase II from MIN6 cells has one subunit of 55 kDa,
      determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, is
      autophosphorylated in a Ca2+/CaM-dependent manner, and phosphorylates several
      substrates that serve for rat brain CaM kinase II. In the membrane fraction of
      MIN6 cells, we identified a 84-kDa protein that was immunoreactive with the
      antirat brain synapsin I antibody. One-dimensional phosphopeptide mapping by
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography
      revealed the sites of the phosphorylation by cAMP-dependent protein kinase (cAMP
      kinase) and that by CaM kinase II to be site 1 (10 kDa) and site 2 (30 kDa),
      respectively, therefore, the same as for rat brain synapsin I. In this context,
      we tentatively termed it synapsin I-like protein. In 32P-labeled cells, nonfuel
      insulin secretagogues, such as ionomycin, KCl, and tolbutamide, and a fuel
      secretagogue, glucose, stimulated autophosphorylation of CaM kinase II and the
      phosphorylation of synapsin I-like protein. These secretagogues potentiated the
      Ca(2+)-independent activity of CaM kinase II and secretion of insulin from MIN6
      cells. The 84-kDa protein is apparently a newly identified member of the synapsin
      family. We suggest that CaM kinase II regulates insulin secretion via
      phosphorylation of synapsin I-like protein.

PMID- 7649086
TI  - Thyroid-stimulating hormone activates phospholipase D in FRTL-5 thyroid cells via
      stimulation of protein kinase C.
AB  - We studied whether TSH or phorbol myristate acetate (PMA) stimulates the
      hydrolysis of phospholipids, predominantly phosphatidylcholine, via phospholipase
      D (PLD) in FRTL-5 thyroid cells and whether this occurs as a consequence of
      protein kinase C (PKC) activation. FRTL-5 thyroid cells were labeled with
      [3H]myristate followed by incubation with 200 mM ethanol before the addition of
      agonist. PLD activity was assessed by the measurement of [3H]phosphatidylethanol
      from [3H]phospholipid (predominantly [3H]phosphatidylcholine). Compared to
      control values, bovine TSH (100 microU/ml) increased PLD activity by 480% and
      600%, respectively, after 30 and 60 min of exposure. Studies with purified human
      and bovine TSH revealed similar results, indicating that this effect was due to
      TSH itself. PMA (100 nM) increased PLD activity at 10 min (630% of the control
      value), and this effect persisted up to 60 min (600% of the control value). To
      determine whether the effects of TSH on PLD occurred as a consequence of PKC
      activation, FRTL-5 thyroid cells were preincubated with the PKC inhibitor,
      chelerythrine (1 microM for 10 min), or were pretreated for 24 h with PMA (100
      nM) to down-regulate PKC. PLD stimulation by TSH and PMA was largely abolished by
      such treatments. These studies indicate that in FRTL-5 thyroid cells, TSH and PMA
      are capable of stimulating PLD, and that PKC activation is responsible for this
      stimulation. The role of PLD activation could be to amplify and prolong the PKC
      signal by further production of diacylglycerol.

PMID- 7649087
TI  - Regulation of rat mineralocorticoid receptor expression in neurons by
      progesterone.
AB  - We have studied the effects of progesterone on the transcription of the
      mineralocorticoid receptor (MR) gene in neurons in vitro and in vivo.
      Progesterone treatment caused a 2.5-fold increase in activity of the MR promoter
      in transiently transfected N2A neuroblastoma cells. Similarly, MR promoter
      activity in GH3 pituitary cells was increased 2-fold after treatment with the
      specific progesterone receptor agonist R5020, with an even greater induction
      after priming with 17 beta-estradiol. Progesterone treatment also produced a dose
      dependent increase in MR messenger RNA (mRNA) levels in primary hippocampal
      neuron cultures. In vivo, chronic administration of progesterone to estrogen
      primed adrenalectomized/ovariectomized rats significantly increased MR mRNA
      levels in all hippocampal subfields, as determined by semiquantitative in situ
      hybridization histochemistry. Whereas chronic estradiol treatment decreased MR
      mRNA levels in the hippocampus, progesterone administration in the absence of
      estradiol priming was without any effect. These results indicate that 1)
      progesterone increases MR mRNA levels in vitro and in vivo; 2) the stimulatory
      effects of progesterone are at least partially mediated by induction of MR
      promoter activity; and 3) estrogen priming is essential for the effect of
      progesterone upon MR mRNA in vivo. Further, they suggest the possibility of
      heterologous regulation of corticosteroid receptors in the brain, whereby the
      responsiveness of the limbic-hypothalamo-pituitary-adrenal system to
      corticosteroids may be modulated.

PMID- 7649088
TI  - Gene expression of 17 beta-hydroxysteroid dehydrogenase type 2 isozyme in primary
      cultures of human trophoblasts predicts different mechanisms regulating type 1
      and type 2 enzymes.
AB  - Two 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) genes, types 1 and 2, have
      been cloned. The two isozymes show a 30% sequence homology but differ markedly in
      their kinetic properties. To date, the steroidogenic capacity of the placenta has
      been associated with syncytium formation. In this study, we have investigated 17
      beta-HSD type 1 and type 2 gene expression during trophoblast differentiation in
      culture. We observed that term placenta and fetal cotyledons contain large
      amounts of both messenger RNAs (mRNAs). In culture, the type 1 gene is expressed
      concurrent with syncytium formation. However, type 2 expression is barely
      detectable in freshly isolated cytotrophoblasts and undetectable in
      syncytiotrophoblasts. Incubation of trophoblasts with progesterone and estradiol
      increased type 1 mRNA but did not restore 17 beta-HSD type 2 expression. 17 beta
      HSD activities with substrates that differentiate the type 1 and type 2 enzymes
      correlated with the gene expression results. Type 1 activity decreased in freshly
      isolated trophoblasts by 2-fold and remained at these levels throughout the
      culture period. However, when compared with levels measured in term microsomes,
      type 2 activity decreased by 20-fold in freshly isolated cells and decreased
      again in culture by 5-fold. The expression pattern of 17 beta-HSD type 1 and type
      2 activity in trophoblasts in culture suggests differing mechanisms regulate type
      1 and type 2 mRNA levels.

PMID- 7649089
TI  - Reconstructions of populations of luteinizing hormone releasing hormone neurons
      in young and middle-aged rats reveal progressive increases in subgroups
      expressing Fos protein on proestrus and age-related deficits.
AB  - Fos expression has been used as a marker of activation of neuroendocrine cells
      including LHRH neurons. In this study, Fos protein was localized within LHRH
      neurons in young and middle-aged rats to trace the temporal and spatial pattern
      of LHRH neuronal activation associated with the preovulatory LH surge. Animals
      were killed during the late morning, afternoon, and evening of proestrus. Dual
      immunocytochemical protocols localized LHRH and LHRH/Fos neurons, and computer
      assisted methods were used to reconstruct forebrain populations of single- and
      double-labeled LHRH neurons. Although a significant increase in the number of
      LHRH/Fos neurons was noted by evening in both age groups, a greater increase was
      observed in young (12% in morning, 28% in afternoon, and 62% by evening) compared
      with aging females (5% in morning, 10% in afternoon, and 40% by evening).
      Reconstructions of LHRH and LHRH/Fos neurons revealed time- and age-dependent
      differences in Fos expression within LHRH neurons. In young females, LHRH/Fos
      neurons were restricted to central regions of the population of LHRH neurons on
      the morning of proestrus. By evening, Fos expression was also observed in more
      peripheral and caudal LHRH neurons. In middle-aged females, Fos expression was
      restricted to ventral subgroups of LHRH neurons on the afternoon of proestrus. By
      evening, more LHRH neurons contained Fos protein, however, few were located in
      the dorsal aspect of the population. These data trace the progressive increase in
      activation of LHRH neurons during the preovulatory LH surge in young females and
      reveal deficits in this pattern of activation by middle age.

PMID- 7649090
TI  - Basic fibroblast growth factor is a neurotropic factor in GT1 gonadotropin
      releasing hormone neuronal cell lines.
AB  - Basic fibroblast growth factor (bFGF) plays an important role in development of
      the central nervous system and is neurotropic for a variety of neurons. In this
      study, we investigated whether bFGF is neurotropic for GT1 GnRH neuronal cell
      lines and if these cells express functional FGF receptors (FGFRs). The GT1 cell
      lines generated by genetically targeted tumorigenesis display highly
      differentiated properties of GnRH neurons. Addition of 2 and 10 ng/ml bFGF
      increased neurite outgrowth of GT1-7 cells and resulted in a significant increase
      of GT1 cell survival in serum-free medium. However, bFGF had no effect on
      [3H]thymidine incorporation at 24 or 48 h. RNase protection assays using
      riboprobes specific for murine FGFRs 1-3 showed that GT1 cells express FGFRs 1
      and 3 but not 2. Occupancy of FGFRs with 10 ng/ml bFGF stimulated the sustained
      tyrosine phosphorylation of both the 42- and 44-kilodalton mitogen-activated
      protein kinases (MAPKs) for up to 6 h as shown by Western blot analysis. In
      addition, phosphorylation of the MAPKs was associated with enzyme activation as
      shown by an in-gel MAPK assay. GT1-1 and GT1-7 cells also express messenger RNA
      for bFGF, although the level of bioactive bFGF synthesized by GT1 cells appears
      suboptimal because GT1 cells can further respond to exogenously added bFGF. Thus,
      we have demonstrated that bFGF is a neurotropic factor in GT1 GnRh neuronal cell
      lines, raising the possibility that bFGF may play a role in the neurobiology of
      GnRH neurons.

PMID- 7649091
TI  - Effect of long-acting antagonists of growth hormone (GH)-releasing hormone on GH
      and cyclic adenosine 3',5'-monophosphate release in superfused rat pituitary
      cells.
AB  - In a recent study, investigating the time course of both GH and cAMP secretion
      induced by GH-releasing hormone (GHRH) in the superfusion system, we found that
      the amount of cAMP liberated from the cells was not proportional to GH release
      and that cAMP discharged after a GHRH pulse alone cannot maintain the release of
      GH. In the present study, two potent antagonists of GHRH, MZ-4-71 ([Ibu0,D
      Arg2,Phe(4-Cl)6,Abu15,Nle27]human GHRH-(1-28)Agm) and MZ-4-243 ([Nac0,D
      Arg2,Phe(4-Cl)6,Abu15,Nle27]human GHRH-(1-28)Agm) were evaluated for their long
      term effect in the superfusion system and for their ability to influence the
      release of GH and cAMP. Our present findings showed that after a 9-min
      preincubation, antagonist MZ-4-71 and MZ-4-243 at 3 and 1 nM, respectively,
      caused an inhibition of GH release, stimulated by 1 nM GHRH, similar to that
      caused by the 100-nM dose of the standard antagonist ([Ac-Tyr1,D-Arg2]human GHRH
      (1-29)NH2). The standard antagonist at 100 nM did not influence the GHRH-induced
      GH response 30 min later, and the inhibition caused by MZ-4-71 at 30 nM decreased
      gradually to 30% 120 min after the treatment, but the 30-nM dose of MZ-4-243
      reduced the GH response by more than 90% even 270 min after its administration.
      During a 2-h incubation with 1 nM GHRH in combination with a 30-min infusion of
      the standard antagonist, MZ-4-71, MZ-4-243, or somatostatin, from the 30th to the
      60th min, the decrease in GH discharge preceded the inhibition of cAMP release.
      After infusion of the antagonists or somatostatin was stopped, GH release resumed
      sooner than that of cAMP. Simultaneous determinations of cAMP and GH in the
      samples showed that changes in GH levels were never preceded by a rise or
      decrease in cAMP release, in contrast to existing information. The participation
      of more than one signal transduction mechanism in the mediation of the effect of
      GHRH is very likely, and the balance of these mechanisms may vary with the dose
      and duration of stimulation.

PMID- 7649092
TI  - Quantitative analysis of androgen receptor messenger ribonucleic acid in
      developing Leydig cells and Sertoli cells by in situ hybridization.
AB  - Testosterone produced by Leydig cells is critical for the maintenance of
      spermatogenesis by Sertoli cells throughout adulthood in the rat. However, the
      presence of androgen receptors (AR) in Leydig cells in prepubertal rats suggests
      additional roles for androgen in early Leydig cell function and differentiation.
      In the present study, AR messenger RNA (mRNA) was directly measured by in situ
      hybridization in sections of rat testes at three developmental stages: on day 21
      postpartum, when Leydig cells exist as mesenchymal-like progenitors; on day 35,
      when they are still immature, producing low amounts of testosterone; and on day
      90, when they are fully functional in the sexually mature animal. Testicular AR
      mRNA was detected in Leydig cells, pericytes, peritubular myoid cells, and
      Sertoli cells. On day 90, AR mRNA levels in Sertoli cells varied with the cycle
      of the seminiferous epithelium, achieving peak intensity at stages VII-VIII.
      Measurements were made by image analysis and expressed as integrated signal
      intensities per unit labeled area (mean +/- SEM; n = 3 rats at each age). The
      results showed that levels of Leydig cell and Sertoli cell AR mRNA change
      significantly during development (P < 0.05). Leydig cell AR mRNA was intermediate
      on day 21 (at 17.3 +/- 0.7), highest on day 35 (at 26.9 +/- 1.6), and lowest on
      day 90 (at 11.8 +/- 1.1). The trend for isolated Leydig cells from these three
      ages was identical. In contrast, Sertoli cell AR mRNA was lowest on day 21 (at
      19.3 +/- 1.0), intermediate on day 35 (at 24.5 +/- 1.4), and highest on day 90
      (at 36.9 +/- 0.5). In Leydig cells, the highest level of AR mRNA was present
      during puberty, whereas the greatest amount of AR mRNA in Sertoli cells was
      present on day 90. This indicates that Leydig cells and Sertoli cells use
      different mechanisms to maintain AR levels. We infer from these data that Leydig
      cells are maximally sensitive to androgen during puberty, which is consistent
      with our hypothesis that androgens facilitate their differentiation.

PMID- 7649093
TI  - Regulation of the pituitary-specific transcription factor GHF-1/Pit-1 messenger
      ribonucleic acid levels by growth hormone-secretagogues in rat anterior pituitary
      cells in monolayer culture.
AB  - Pituitary-specific expression of the GH gene is dependent on a pituitary-specific
      transcription factor GH factor-1 (GHF-1), a homeodomain protein also known as
      pituitary-specific transcription factor-1 (Pit-1). The aim of this study was to
      investigate the regulation of GHF-1 messenger RNA (mRNA) levels in primary
      monolayer cultures of rat anterior pituitary cells. Specifically, in addition to
      direct activators of second messenger signaling systems, we studied the effects
      of different hormones, all of which are known to be involved in the regulation of
      somatotroph cell function. We found that GH-releasing hormone (GHRH) increased
      GHF-1 mRNA levels in a time- and dose-dependent fashion. GHF-1 mRNA levels were
      increased 2.5-fold (P < 0.01) after incubation for 2 h with 10(-8) M GHRH. Longer
      incubations (6, 12, or 24 h) with GHRH failed to show a similar stimulatory
      effect. A significant increase in GHF-1 mRNA concentration (1.7-fold, P < 0.01)
      was observed after a 2-h treatment with physiological concentrations (10(-11) M)
      of GHRH. The action of GHRH seems to occur at the transcriptional level without
      the need of protein synthesis. Thus, treatment of cells with actinomycin D (5
      micrograms/ml) completely abolished GHRH-induced increase in GHF-1 mRNA levels.
      Cycloheximide (23 micrograms/ml) alone increased GHF-1 mRNA levels (6-fold
      increase after treatment for 12 h, P < 0.01), as well as potentiating GHRH
      induced increase in GHF-1 mRNA concentration (9-fold increase after treatment
      with GHRH plus cycloheximide for 12 h, P < 0.01). The effect of GHRH on GHF-1
      mRNA levels could be mimicked by direct activators of second messenger signaling
      systems such as forskolin (10(-5) M) or the phorbol ester tumor promoter
      tetradecanoyl phorbol acetate (TPA) (10(-6) M). Other peptides such as pituitary
      adenylate cyclase activating polypeptide-38 (10(-7) M) but not GHRP-6 (10(-10) to
      10(-5) M), were also able to increase GHF-1 mRNA levels. Treatment of the cells
      with somatostatin (10(-6) M) for either 2 or 48 h failed to modify basal or GHRH
      induced GHF-1 mRNA levels. In contrast, pretreatment of the cells with insulin
      like growth factor-1 (5 nM) inhibited basal GHF-1 mRNA concentration as well as
      completely blunting the subsequent response to cells exposed to GHRH for 2 h.
      These data demonstrate that GHRH, acting at the transcriptional level and through
      a mechanism not dependent on protein synthesis, plays a stimulatory role on GHF-1
      mRNA levels.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7649094
TI  - Rat insulin turnover in vivo.
AB  - Zucker lean and obese rats were injected under pentobarbital anesthesia with 125I
      labeled insulin; at timed intervals from 30 to 120 sec, blood samples were
      extracted and used for the estimation of insulin levels by RIA. A group of rats
      from each series was maintained under a constant infusion of noradrenaline. For
      each insulin determination, a duplicate blood sample containing the same amount
      of insulin as that used in the RIA, but without the radioactive label, was used
      as a blank for insulin measurement. The radioactivity in these tubes was then
      used for the measurement of insulin label per ml blood. From plasma label decay
      curves and insulin concentrations, the insulin pool size, half-life, and rate of
      degradation were calculated. Obese rats had higher insulin levels (2.43 nM) and
      showed less effect of noradrenaline than their lean counterparts, in which
      insulin distribution volume shrank with noradrenaline treatment. The half-life of
      plasma insulin was similar in all groups (range, 226-314 sec). Pool size and
      overall degradation rates were higher in obese (198 femtokatals) than in lean
      rats (28 femtokatals). It is postulated that obese rats synthesize and cleave
      much more insulin than lean controls despite their higher circulating levels of
      insulin.

PMID- 7649095
TI  - Regulation of hypothalamic and pituitary corticotropin-releasing hormone receptor
      messenger ribonucleic acid by adrenalectomy and glucocorticoids.
AB  - The effects of adrenalectomy and glucocorticoids on the regulation of
      corticotropin-releasing hormone (CRH) receptor expression in the hypothalamic
      paraventricular nucleus (PVN) and pituitary were studied by in situ hybridization
      in the rat using a complementary RNA probe directed toward the coding region of
      the type 1 CRH receptor. Eighteen hours after adrenalectomy, CRH receptor
      messenger RNA (mRNA) expression in the PVN was significantly increased, whereas
      longer term adrenalectomy (4 and 6 days) had no effect. This transient effect of
      adrenalectomy was prevented by glucocorticoid replacement. In intact rats, 4 h
      after immobilization for 1 h or a single ip hypertonic saline injection, CRH
      receptor mRNA in the PVN markedly increased (P < 0.01), an effect that was
      unchanged by adrenalectomy (4 or 6 days) or dexamethasone injection (100
      micrograms at -14 and 50 micrograms at -1 h) before stress. In the pituitary, CRH
      receptor mRNA levels decreased transiently after adrenalectomy (-62% after 18 h),
      returning to basal levels 4 or 6 days after adrenalectomy. The early decrease was
      prevented by glucocorticoid replacement. In intact rats, dexamethasone (100
      micrograms, sc) caused a significant decrease in pituitary CRH receptor mRNA
      levels 2-10 h after injection, returning to basal levels after 15 h. On the other
      hand, dexamethasone (5-300 micrograms, sc) had no effect on pituitary CRH
      receptor mRNA levels 18 h after injection. The data show that although stress
      stimulation of CRH mRNA in the PVN is glucocorticoid independent, basal levels
      are likely to be under dual, transcriptional and posttranscriptional, control by
      glucocorticoids. In the pituitary, changes in hypothalamic CRFs probably play a
      major role in the control of CRH receptor mRNA levels during manipulations of
      circulating glucocorticoids levels. In addition, the inability of long term
      adrenalectomy and glucocorticoid administration to modify pituitary CRH receptor
      mRNA levels suggests that CRH receptor down-regulation observed under these
      experimental conditions depends mainly on translational and post-translational
      events rather than receptor mRNA levels.

PMID- 7649096
TI  - Parathyroid hormone (PTH)/PTH-related peptide receptor density modulates
      activation of phospholipase C and phosphate transport by PTH in LLC-PK1 cells.
AB  - We showed previously that a single species of cloned PTH/PTH-related peptide
      (PTHrP) receptors, when stably expressed in LLC-PK1 kidney cells, couples to
      multiple second messenger signals and biological responses. To address the
      linkages of individual messenger signals to specific biological responses in
      these cells, we examined the relations among PTH/PTHrP receptor expression, PTH
      activated phospholipase C (PLC) and adenylyl cyclase, and PTH-regulated phosphate
      transport in LLC-PK1 cells that stably express cloned rat PTH/PTHrP receptors.
      Among 18 such subclones, PTH stimulation of intracellular cAMP accumulation was
      nearly equivalent, despite differences in receptor density ranging from 20,000
      400,000 sites/cell. In contrast, activation of PLC by PTH was directly and
      continuously dependent upon receptor density. PTH-stimulated phosphate uptake
      also was strongly dependent upon receptor expression, correlated well with PLC
      activity, was mimicked by active phorbol esters but not by cAMP analogs or
      forskolin, and was strikingly inhibited by the protein kinase C inhibitor,
      staurosporine. The peptide analog [Arg2]human PTH-(1-34), which significantly
      stimulated cAMP accumulation but failed to activate PLC, also did not increase
      phosphate uptake. We conclude that in LLC-PK1 cells, PTH-modulated PLC
      activation, unlike adenylyl cyclase activation, is strongly dependent upon
      PTH/PTHrP receptor density. This feature is reflected in the analogous relation
      between receptor density and PTH regulation of phosphate uptake, which appears to
      be mediated via a PKC-dependent pathway in these transfected cells. The results
      suggest that regulation of PTH/PTHrP receptor expression on target cells may
      provide a mechanism for altering the character as well as the magnitude of the
      signaling response to the hormone.

PMID- 7649097
TI  - The prolactin receptor in the fetal rat: cellular localization of messenger
      ribonucleic acid, immunoreactive protein, and ligand-binding activity and
      induction of expression in late gestation.
AB  - The cellular distribution and developmental expression of the PRL receptor (PRLR)
      in the late gestational fetal rat were examined by in situ hybridization,
      immunohistochemistry, and radioligand binding. Antisense and sense strand RNA
      probes encoding the long and short isoforms of the rat PRLR were hybridized to
      tissue sections under stringent conditions. Messenger RNA (mRNA) encoding the two
      isoforms of the receptor was expressed widely in tissues derived from all three
      germ layers; these included various tissues not known previously to contain
      lactogenic receptors, such as the olfactory neuronal epithelium and olfactory
      bulb, trigeminal and dorsal root ganglia, cochlear duct, brown adipose tissue,
      submandibular glands, whisker follicles, tooth primordia, and proliferative and
      maturing chondrocytes of developing bones. Prominent expression of PRLR mRNA was
      also detected in the fetal adrenal cortex, gastrointestinal and bronchial
      mucosae, renal tubular epithelia, choroid plexus, thymus, liver, pancreas, and
      epidermis. Immunohistochemical studies using monoclonal anti-PRLR antibodies
      demonstrated that the distribution of PRLR immunoreactivity was similar to that
      of PRLR mRNA, suggesting that the PRLR mRNA is translated to receptor protein in
      the fetus in vivo. The encoding of functional PRL receptor proteins by fetal PRLR
      mRNA was revealed by the presence of specific rat placental lactogen II-binding
      sites in fetal adrenal cortex, renal tubules, small intestinal villi, pancreatic
      ductules and islets, hepatic parenchymal cells, choroid plexus ependymal cells,
      and microsomal fractions of fetal lung and thymus. Levels of expression of PRLR
      mRNA and protein increased between days 17.5 and 20.5 of gestation in a number of
      fetal tissues, including the adrenal, pancreas, small intestine, pituitary,
      thymus, liver, and submandibular gland. The widespread expression of the PRLR in
      the fetal rat and the induction of receptor expression in late gestation suggest
      novel roles for the lactogenic hormones in fetal and neonatal development.

PMID- 7649098
TI  - Regulation of insulin-like growth factor I transcription by cyclic adenosine
      3',5'-monophosphate (cAMP) in fetal rat bone cells through an element within exon
      1: protein kinase A-dependent control without a consensus AMP response element.
AB  - Insulin-like growth factor I (IGF-I) is a locally synthesized anabolic growth
      factor for bone. IGF-I synthesis by primary fetal rat osteoblasts (Ob) is
      stimulated by agents that increase the intracellular cAMP concentration,
      including prostaglandin E2 (PGE2). Previous studies with Ob cultures demonstrated
      that PGE2 enhanced IGF-I transcription through selective use of IGF-I promoter 1,
      with little effect on IGF-I messenger RNA half-life. Transient transfection of Ob
      cultures with an array of promoter 1-luciferase reporter fusion constructs has
      now allowed localization of a potential cis-acting promoter element(s)
      responsible for cAMP-stimulated gene expression to the 5'-untranslated region (5'
      UTR) of IGF-I exon 1, within a segment lacking a consensus cAMP response element.
      Our evidence derives from three principal observations: 1) a transfection
      construct containing only 122 nucleotides (nt) of promoter 1 and 328 nt of the 5'
      UTR retained full PGE2-stimulated reporter expression; 2) maximal PGE2-driven
      reporter expression required the presence of nt 196 to 328 of exon 1 when tested
      within the context of IGF-I promoter 1; 3) cotransfection of IGF-I promoter
      luciferase-reporter constructs with a plasmid encoding the alpha-isoform of the
      catalytic subunit of murine cAMP-dependent protein kinase (PKA) produced results
      comparable to those seen with PGE2 treatment, whereas cotransfection with a
      plasmid encoding a mutant regulatory subunit of PKA that cannot bind cAMP blocked
      PGE2-induced reporter expression. Deoxyribonuclease I footprinting of the 5'-UTR
      of exon 1 demonstrated protected sequences at HS3A, HS3B, and HS3D, three of six
      DNA-protein binding sites previously characterized with rat liver nuclear
      extracts. Of these three regions, only the HS3D binding site is located within
      the functionally identified hormonally responsive segment of IGF-I exon 1. These
      results directly implicate PKA in the control of IGF-I gene transcription by PGE2
      and identify a segment of IGF-I exon 1 as being essential for this hormonal
      regulation.

PMID- 7649099
TI  - Thyroxine-dependent regulation of integrin-laminin interactions in astrocytes.
AB  - Adhesive interactions among the extracellular matrix protein laminin, cell
      surface receptors known as integrins, and the microfilament network play a
      fundamental role in the regulation of neural cell migration during brain
      development. The disturbed neuronal migration that occurs when thyroid hormone is
      lacking during early neonatal life contributes to the profound morphological
      alterations characteristic of the cretinous brain. We have previously shown that
      thyroid hormone determines the organization of the microfilament network in
      astrocytes by regulating the polymerization of F-actin fibers. In this paper, we
      examined whether T4-dependent alterations in microfilament organization affected
      astrocyte-laminin interactions. We show that T4-treated astrocytes readily
      attached to laminin, whereas attachment of thyroid hormone-deficient cells to
      laminin was delayed. T4-dependent cell attachment to laminin was completely
      abolished by blocking integrin recognition sites with site-specific peptides or
      by depolymerizing the microfilaments with dihydrocytochalasin B. We also show
      that T4 was required for integrin clustering and focal contact formation in
      astrocytes attached to laminin. Thus, T4 dynamically regulates interactions
      between integrins and laminin via modulation of microfilament organization in
      astrocytes. The T4-dependent regulation of laminin-integrin interactions provides
      a mechanism by which this morphogenic hormone can influence neuronal migration
      and development.

PMID- 7649100
TI  - Three high threshold calcium channel subtypes in rat corticotropes.
AB  - In this study on highly enriched populations of cultured rat corticotropes, Ca2+
      channel inhibitors were used to identify subtypes of the high threshold Ca2+
      channel current under voltage clamp conditions. From a holding potential (-50 mV)
      that eliminated the low threshold T-type current, 52 +/- 4% of the total current
      in 10 mM Ba2+ was mediated by dihydropyridine-sensitive L-type Ca2+ channels.
      Blockade of this current was half-maximal at a nifedipine concentration of 187
      nM. omega-Agatoxin-IVA (20 nM) maximally inhibited 28 +/- 3% of the total
      current. This high sensitivity to omega-agatoxin-IVA indicates that this
      noninactivating current is mediated by P-type Ca2+ channels. A very high
      threshold, noninactivating current (23 +/- 4% of the total Ba2+ current) remained
      after maximal inhibition of L- and P-type Ca2+ channels. This current was also
      resistant to toxins that inhibit N (omega-conotoxin-GVIA)- and Q (omega-conotoxin
      MVIIC)-type Ca2+ channels. Because this current had slow activation kinetics and
      voltage dependence very different from those of the L- and P-type currents in
      these cells, it was probably mediated by a third unclassified Ca2+ channel
      subtype (or subtypes). It is concluded that the high threshold current in
      corticotropes is due to the presence of at least three different Ca2+ channel
      subtypes.

PMID- 7649101
TI  - Corticotropin-releasing hormone stimulation of Ca2+ entry in corticotropes is
      partially dependent on protein kinase A.
AB  - The modulation of membrane excitability and cytosolic Ca2+ levels by
      corticotropin-releasing hormone (CRH), (Bu)2cAMP (dBcAMP), and forskolin was
      examined in enriched populations of cultured rat anterior pituitary
      corticotropes. CRH (2 or 20 nM), dBcAMP (1 and 5 mM), and forskolin (10 microM)
      caused a long lasting membrane depolarization accompanied by the onset of cell
      firing in quiescent cells or by increased firing frequency in spontaneously
      active cells. All three substances also increased cytosolic Ca2+ levels by
      increasing the frequency and amplitude of cytosolic Ca2+ transients. These
      results are consistent with a previous report on human corticotrope tumor cells
      demonstrating that CRH-induced action potentials lead to enhancement of Ca2+
      uptake through voltage-dependent Ca2+ channels. Preincubation with (N-[2-(p
      bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H-89), an inhibitor of cAMP
      dependent protein kinase A, did not inhibit the CRH-induced depolarization, but
      attenuated the CRH-induced increase in action potential frequency. H-89 inhibited
      CRH-induced changes in cytosolic Ca2+ by 69% in spontaneously active cells and by
      83% in quiescent cells. In contrast, H-89 completely abolished the effects of
      dBcAMP and forskolin on membrane potential and cytosolic Ca2+ levels. It is
      concluded that activation of protein kinase A mediates all of the response to
      dBcAMP and forskolin, but only a portion of the response to CRH. The portion of
      the response to CRH that is resistant to H-89 is mediated by a cAMP-independent
      mechanism.

PMID- 7649102
TI  - Inhibitory effects of interleukin-1 on growth hormone secretion in conscious male
      rats.
AB  - Although various pathophysiological effects of interleukin (IL) on the CRF-ACTH
      adrenal axis and gonadotropin secretion have been studied extensively, the
      effects of IL on GH secretion still remain to be elucidated. We investigated the
      possible effects of IL on GH secretion in six groups of conscious rats. In four
      groups, IL was administered by continuous iv infusion and in the other two, by
      intracerebroventricular injection. Saline-treated rats served as controls for
      these groups. Sequential blood sampling was performed every 20 min in all groups,
      and the plasma GH concentration was determined by RIA. The expression of
      hypothalamic c-fos protein in a separate group was examined by
      immunohistochemistry. Continuous infusion of both IL-1 alpha and IL-1 beta (10
      ng/min) significantly inhibited GH surges. The plasma IL-1 level was elevated to
      2-3 ng/ml. Continuous iv infusion of IL-2 and IL-6 had no effect on GH secretion.
      The intracerebroventricular injection of both IL-1 alpha and IL-1 beta
      significantly inhibited GH surges, and the inhibitory effect was much greater for
      IL-1 beta than for IL-1 alpha. Continuous iv infusion of IL-1 beta markedly
      stimulated c-fos expression in specific hypothalamic nuclei, particularly in the
      paraventricular nucleus. These findings suggest that, in the rat, IL-1 inhibits
      GH secretion through its peripheral and central actions.

PMID- 7649103
TI  - Mechanism of glucose-induced biphasic insulin release: physiological role of
      adenosine triphosphate-sensitive K+ channel-independent glucose action.
AB  - The mechanism of glucose-induced biphasic insulin release by the B cell was
      investigated using isolated rat pancreatic islets. In perifusion experiments,
      16.7 mM glucose in combination with 25 mM K+ transformed the high K(+)-induced
      monophasic insulin release into a biphasic one in the presence of diazoxide (Dz),
      an ATP-sensitive K+ channel opener. Inclusion of Dz during the initial 6 min of
      glucose stimulation abolished the first phase, but was without effect on the
      second phase. In batch incubation experiments, fuels, including 16.7 mM glucose,
      6 mM D-glyceraldehyde, and 10 mM 2-ketoisocaproate, but not sulfonylurea, caused
      time-dependent potentiation of the B cell so that the response to 25 mM K+,
      applied later, was increased in the fuel-primed islets. Inclusion of Dz or
      lowering extracellular Ca2+ (to micromolar range) during the priming, which
      eliminates the initiation of insulin release, did not eradicate the potentiation.
      We conclude that high glucose closes ATP-sensitive K+ channels, leading to
      membrane depolarization, Ca2+ influx, and initiation of insulin release (first
      phase), and subsequently self-augments insulin release in an ATP-sensitive K+
      channel-independent manner (second phase), acting at steps distal to cytosolic
      Ca2+ elevation. The biphasic insulin release is thus generated by an interaction
      of ATP-sensitive K+ channel-dependent and -independent glucose actions.

PMID- 7649104
TI  - Disruption of hypothalamic-pituitary-adrenocortical system in transgenic mice
      expressing type II glucocorticoid receptor antisense ribonucleic acid permanently
      impairs T cell function: effects on T cell trafficking and T cell responsiveness
      during postnatal development.
AB  - We used transgenic mice with impaired corticosteroid receptor function, caused by
      expression of type II glucocorticoid receptor (GR) antisense RNA, to study the
      role of glucocorticoid feedback during the developmental maturation of
      hypothalamus-pituitary-adrenal-immune functions. These mice have increased plasma
      concentrations of ACTH and corticosterone as well as reduced GR binding capacity.
      In control mice, a strong sex dimorphism in the development of GR gene expression
      is apparent, and in males between postnatal days 9-36, the GR gene transcript
      concentration is approximately twice that in female mice. Endogenous GR messenger
      RNA levels were markedly reduced in transgenic mice, and the sex dimorphism was
      abolished. An abnormal developmental pattern of adrenal secretory activity
      accompanied the postnatal maturation of the hypothalamic-pituitary-adrenocortical
      system of the transgenic mice, and high plasma corticosterone levels were
      measured at early postnatal ages through adulthood. Inefficient glucocorticoid
      inhibitory action on the immune axis was supported by both the inability of high
      circulating levels of corticosterone to reduce thymus weight and the failure of
      dexamethasone to influence in vitro thymocyte and splenocyte cell proliferation.
      Alterations in thymocyte trafficking/migration in transgenic mice was supported
      by flow cytometric analysis of the distribution of phenotypically distinct
      lymphocyte subsets accompanying the postnatal maturation of the thymus. A marked
      increase in CD4+CD8+ double positive cells and a 2-fold increase in the CD4/CD8
      (helper/suppressor) ratio caused by a 40-60% increase in the CD4+CD8- (T helper)
      subset and a decrease in the CD4-CD8+ (T suppressor) subset, was seen. Moreover,
      in transgenic mice, an absence of sexual dimorphism and a significantly increased
      immune reactivity were observed. The present study shows that disruption of the
      hypothalamic-pituitary-adrenocortical system has both developmental and permanent
      effects on T cell function characterized by a shifting of the T cell balance
      toward the CD4+CD8- helper-inducer phenotype coupled with hyperresponsiveness of
      the T (helper) cell compartment. These findings point to the GR as a major factor
      in the counterregulatory feedback loop controlling autoaggressive immune
      responses and underline the potential modulatory role of sex steroids in this
      feedback regulation and in the pathogenesis of autoimmune diseases.

PMID- 7649105
TI  - Developmental regulation of steroidogenic enzyme gene expression in the
      periimplantation porcine conceptus: a paracrine role for insulin-like growth
      factor-I.
AB  - During periimplantation, the estrogen biosynthetic capability of the porcine
      conceptus is transient, coincident with morphological development (trophoblast
      elongation), and temporally associated with maximal uterine release of insulin
      like growth factor-I (IGF-I) into the luminal fluid. We investigated the possible
      linkages of conceptus steroidogenesis and IGF-I by characterizing the
      developmental expression of the pig conceptus cytochrome P450 aromatase
      (P450arom) and cytochrome P450 17 alpha-hydroxylase (P45017 alpha) genes during
      periimplantation (days 8, 10, 12, 15, and 18) and the potential regulation by IGF
      I of conceptus P450arom messenger RNA (mRNA) content. Primer pairs derived from
      porcine P450arom and P45017 alpha DNA sequences were used in reverse
      transcription-polymerase chain reaction analysis of conceptuses of differing
      morphologies and developmental stages. RNA transcripts for P450arom and P45017
      alpha were readily detected only in conceptuses obtained at day 12 of pregnancy,
      with RNA levels varying according to morphological stage. P45017 alpha gene
      expression was maximal in spherical conceptuses greater than 5 mm in diameter,
      whereas P450arom mRNA was expressed in small (3-5 mm) and large (6-10 mm)
      spherical (large >> small), as well as day 12, filamentous conceptuses. Using
      primers derived from the human IGF-I receptor (IGF-IR) DNA sequence, constitutive
      expression of IGF-IR mRNA in porcine conceptuses throughout early pregnancy was
      demonstrated. Constitutively low expression of conceptus RNA transcripts for IGF
      I ligand was similarly observed. However, uterine luminal fluid concentrations of
      IGF-I on day 12 were highly correlated with conceptus morphology, with maximal
      IGF-I in uteri possessing filamentous conceptuses. In vitro addition of IGF-I to
      day 12 conceptuses of filamentous or spherical morphologies resulted in distinct
      effects on P450arom mRNA abundance. Filamentous conceptuses had increased amounts
      of P450arom mRNA when treated with IGF-I. In contrast, IGF-I decreased the levels
      of P450arom mRNA in spherical conceptuses. IGF-I treatment did not alter mRNA
      expression of the IGF-IR gene in conceptuses of either morphology. These results
      demonstrate that transient expression of P450arom and P45017 alpha genes in
      perimplantation porcine conceptuses, document the constitutive expression of the
      conceptus IGF-IR gene, and support the involvement of endometrial IGF-I in
      modulation of embryonic P450arom mRNA abundance.

PMID- 7649106
TI  - Variable in vivo regulation of rat vitamin D-dependent genes (osteopontin, Ca,Mg
      adenosine triphosphatase, and 25-hydroxyvitamin D3 24-hydroxylase): implications
      for differing mechanisms of regulation and involvement of multiple factors.
AB  - In these studies, the regulation of renal osteopontin (OPN), intestinal calcium
      pump, and renal and intestinal 25-hydroxyvitamin D3 24-hydroxylase (24OHase) was
      compared to the regulation of calbindin by Northern blot analysis. The time
      course of induction of the calbindins and calcium pump messenger RNAs (mRNAs) in
      vitamin D-deficient rats in response to 1,25-hydroxyvitamin D3 [1,25-(OH)2D3] was
      similar [first induction 3 h after 1,25-(OH)2D3 (200 ng/100 g BW), reaching a
      maximum at 12-24 h]. However, the maximal induction of calbindin mRNA was greater
      (8.2 +/- 1.2-fold) than that of intestinal calcium pump mRNA (21.3 +/- 0.5-fold).
      24-Hydroxylase mRNA showed a different time course of induction by 1,25-(OH)2D3.
      24-Hydroxylase mRNA was undetectable in vitamin D-deficient rat intestine and
      kidney. In intestine, 24OHase mRNA was maximally induced early [3-6 h after 1,25
      (OH)2D3] and did not accumulate long after 1,25-(OH)2D3 administration. Unlike
      the other vitamin D-regulated genes, OPN was uninduced by 1,25-(OH)2D3 in the
      kidney of D-deficient rats. However, in vitamin D-replete rats given 1,25-(OH)2D3
      for 5 days, a significant induction in renal OPN was observed (6.0-fold; P <
      0.01). Developmental studies indicated that renal 24OHase and intestinal calcium
      pump mRNAs, similar to calbindin-D9K mRNA, were induced at 3 weeks of age, the
      time of weaning when active intestinal calcium absorption is induced. A
      comparison of the effect of calcium status showed that low dietary calcium
      resulted in an induction of intestinal calcium pump as well as calbindin-D9K
      mRNA, consistent with the requirement for an increase in intestinal calcium
      absorption during dietary calcium restriction. We next examined gender- and age
      related changes in the expression of these genes. Our results indicate that renal
      OPN mRNA increases markedly in males with aging (10-fold between 3-20 months; P <
      0.01), whereas OPN mRNA levels are unchanged in females. In both males and
      females, significant increases (2.7- to 4.5-fold) in renal 24OHase mRNA were
      observed at 20 months compared to 3 months of age.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 7649107
TI  - Estrogen and phorbol esters regulate amphiregulin expression by two separate
      mechanisms in human breast cancer cell lines.
AB  - The actions of 17 beta-estradiol (E2) and protein kinase C (PKC) appear to
      converge in the regulation of expression of certain growth modulatory genes, such
      as the growth factor amphiregulin (AR). AR is known to modulate cell growth by
      binding to the epidermal growth factor receptor. In the current report we
      established the mechanisms of the PKC-activating phorbol ester tumor promoter, 12
      O-tetradecanoylphorbol-13-acetate (TPA) and the steroid hormone E2 on the
      induction of AR expression in human breast carcinoma cell lines. TPA (100 nM) and
      E2 (1 nM) induce AR messenger RNA (mRNA) expression by 6- to 8-fold and 3- to 6
      fold, respectively, in a time- and dose-dependent manner. In addition,
      immunoreactive AR protein is induced by both TPA and E2 by 6- to 8-fold and 2- to
      4-fold, respectively. The PKC-modulating drugs, bryostatin and H-7, and
      antiestrogens (ICI 164,384 and 4-hydroxytamoxifen) interfere with AR induction by
      TPA and estrogen, respectively. The effects of TPA and E2 on the induction of AR
      mRNA were both closely associated with enhanced transcription of the AR gene.
      However, TPA had an additional effect at the posttranscriptional level by
      stabilizing the AR mRNA. The protein synthesis inhibitor, cycloheximide,
      prevented AR induction by TPA, suggesting that a component of the TPA induction
      of AR is indirect and dependent upon protein synthesis. Conversely, the E2
      induction of AR transcription was found to be a direct response, independent of
      protein synthesis. The results presented herein thus demonstrate that TPA and E2
      are able to stimulate AR gene transcription by two separate mechanisms.

PMID- 7649108
TI  - Luteotropic actions of placental lactogens at midpregnancy in the mouse.
AB  - In this study the luteotropic activity of mouse placental lactogen I (mPL-I) at
      midpregnancy was assessed using in vivo and in vitro methodologies. Ovaries from
      10-day pregnant mice were enzymatically dispersed and plated on fibronectin
      coated wells in serum-free medium. The percentage of ovarian cells that stained
      for the presence of 3 beta-hydroxysteroid dehydrogenase activity was 24.4 +/-
      2.7% at the time of plating and remained constant (26.1 +/- 5.0%) after a 20-h
      attachment period. Two types of 3 beta-hydroxysteroid dehydrogenase-staining
      cells, with distinct differences in size and morphology, were present in the
      culture. Large luteal cells (26-45 microns) were characterized by a small round
      nucleus and spherical shape with abundant cytoplasm. In contrast, small luteal
      cells (< 20 microns) were stellate, with little cytoplasm and a large oval
      nucleus. Basal progesterone secretion was maintained without a change in cellular
      DNA content and cell number for 168 h of culture. Treatment of ovarian cells with
      mPL-I (0.05-10 micrograms/ml) caused a dose-dependent increase in the
      progesterone concentration in the medium. The magnitude and time course of mPL-I
      stimulated progesterone accumulation in culture were dependent on the time after
      plating that mPL-I treatment was initiated. The effects of mPL-II and mouse PRL
      (mPRL) on progesterone production were similar to those of mPL-I. The ability of
      sera from 10-, 14-, and 17-day pregnant mice to maintain progesterone production
      in bromocryptine-treated hysterectomized mice was also examined. Mice were
      hysterectomized on day 9 of pregnancy, and serum progesterone, mPL-I, mPL-II, and
      mPRL concentrations were measured 72 h later. Twice daily injections of 0.5 ml
      day 10 pregnancy serum maintained the circulating progesterone concentration at
      values not different from those present at the time of hysterectomy. In contrast,
      serum progesterone concentrations were not maintained in mice treated with serum
      of 14- or 17-day pregnant mice or with saline. Depletion of mPL-I from day 10
      pregnancy serum by affinity chromatography on an anti-mPL-I column removed all
      luteotropic activity, as determined by the inability of this modified serum to
      maintain the serum progesterone concentration in bromocryptine-treated
      hysterectomized mice. A similar pool of day 10 pregnancy serum chromatographed on
      a nonspecific IgG control column did maintain progesterone production, but at
      somewhat lower concentrations than those present at the time of surgery. These
      studies offer direct evidence that mPL-I and mPL-II are luteotropic and support
      progesterone production at midpregnancy in the mouse.

PMID- 7649109
TI  - The effects of a gonadotropin-releasing hormone antagonist on androgen-binding
      protein distribution and other parameters in the adult male rat.
AB  - The effects of gonadotropins and gonadal steroids on androgen-binding protein
      (ABP) production and its distribution among the epididymis, seminiferous tubule
      fluid (STF), testicular interstitial fluid (TIF), and blood were studied in 300-g
      adult male Sprague-Dawley rats. The rats either received no treatment or their
      pituitary function was suppressed by administration of the GnRH antagonist
      [AcD2Nal,D4ClDPhe2,D3Pal3,Arg5,DGlu6 (AA),D-Ala10]LHRH (antagonist). Other groups
      of rats were treated with hCG, FSH, FSH plus hCG, testosterone, or estradiol,
      alone or together with antagonist. Treatment was conducted for 30 days, after
      which time, ABP was detected by its ability to bind [3H]5 alpha
      dihydrotestosterone. Transport of ABP from the testis to the epididymis was
      inhibited by antagonist administration. Simultaneous treatment with antagonist
      and hCG, or antagonist and hCG plus FSH prevented antagonist-induced inhibition
      of ABP transport. Neither FSH, testosterone, nor estradiol alone was effective in
      this process. Inhibition of ABP transport to the epididymis was accompanied by
      its accumulation within the testis. Treatment with antagonist and FSH resulted in
      a 4.5-fold increase in the concentration of ABP in TIF, but had little effect on
      the amount of ABP in STF, indicating selective secretion of ABP from the basal
      surface of the Sertoli cells. Treatment with antagonist alone, antagonist
      together with testosterone or estradiol, or estradiol alone resulted in increased
      concentrations of ABP in both TIF and STF, but the increase in TIF was
      proportionately greater. Treatment with hCG or FSH plus hCG alone or with
      antagonist not only facilitated ABP transport to the epididymis, but also
      increased TIF levels of ABP above control values. The former treatment resulted
      in increased concentrations of testosterone in TIF, but not in STF. Both
      treatments resulted in testosterone levels in both compartments that were higher
      than those in animals treated with antagonist alone. No treatment had a
      statistically significant effect on blood levels of ABP. About 50% of ABP
      synthesis appears to be constitutive, i.e. is not regulated by hormones. Although
      ABP production continues in the presence of antagonist, its transport to the
      epididymis is halted, indicating that epididymal transport of ABP is a hormone
      dependent process. It is likely that elevated intratesticular levels of
      testosterone or FSH and testosterone acting in concert regulate epididymal
      transport of ABP.

PMID- 7649110
TI  - Microwave stabilization enhances immunocytochemical detection of estrogen
      receptor in frozen sections of macaque oviduct.
AB  - We have found that microwave (MW) stabilization greatly improves detection of the
      estrogen receptor (ER) in frozen sections of rhesus monkey oviduct by
      immunocytochemistry (ICC). Fresh samples of fimbriae were MW-irradiated, frozen,
      and then cryosectioned. The frozen sections were also MW-treated and then fixed
      in a paraformaldehyde-based fixative before ICC processing. A parallel set of
      samples from each monkey were frozen, sectioned and processed for ICC without any
      MW treatment. MW stabilization clearly increased immunostaining intensity with
      either of two ER-specific monoclonal antibodies, namely, H222 and 1D5. The
      greatest increase was noted in tissues collected from spayed or progesterone
      treated animals. An antibody dilution series indicated that MW stabilization
      increased the sensitivity approximately 20- to 40-fold. In addition, we incubated
      spayed macaque fimbriae at 4 C in the presence of 10 nM [3H]Moxestrol and then
      either froze the tissues immediately (non-MW) or treated them with MW. Slide
      mounted cryosections of non-MW and MW-treated tissue were then incubated with
      either a Tris-EDTA buffer (low salt) or the same buffer containing 4 M KCl (high
      salt). The quantity of [3H]Moxestrol-occupied ER extracted from the frozen
      sections by each buffer was determined by a sucrose gradient shift assay. The low
      salt buffer extracted significantly more radiolabeled ER from non-MW sections
      than from MW-treated sections (P < 0.01), whereas the high salt buffer extracted
      equal amounts of ER from both the MW-treated and non-MW sections. MW-irradiation
      enhanced ICC detectability of ER in frozen sections by greatly reducing the
      amount of ER extracted during the various washes used during normal ICC
      processing.

PMID- 7649111
TI  - Rat oxytocin receptor in brain, pituitary, mammary gland, and uterus: partial
      sequence and immunocytochemical localization.
AB  - Partial complementary DNAs of an oxytocin (OT) receptor were cloned from rat
      brain and uterus. The complementary DNAs encoded for the same amino acid
      sequence, which showed a high degree of homology with the human and porcine
      uterine OT receptors, except for a region in the third intracellular loop.
      Antibodies were raised against nonoverlapping sequences of the third
      intracellular loop of this rat OT receptor. Using these antisera, OT receptor
      expression was demonstrated in the brain, pituitary, mammary gland, and uterus by
      immunocytochemistry. In the brain, several areas including the ventromedial
      hypothalamus, the bed nucleus of the stria terminalis, the ventral pallidum, the
      paraventricular nucleus, and the dorsal part of the supraoptic nucleus,
      demonstrated OT-receptor immunoreactivity. However, no immunoreactivity was
      detected in two areas of the brain known to contain dense OT-binding sites by
      receptor autoradiography studies: the ventral hippocampus and the central nucleus
      of the amygdala. In the pituitary, both the anterior and posterior lobes were
      positive for OT receptor immunoreactivity, whereas the intermediate lobe was
      negative. These results demonstrate that the same receptor type is expressed in
      both peripheral OT target tissues and the brain, and also suggest the possibility
      that a different OT receptor subtype may be present in some areas of the brain.

PMID- 7649112
TI  - The effects of recombinant follicle-stimulating hormone on the restoration of
      spermatogenesis in the gonadotropin-releasing hormone-immunized adult rat.
AB  - The role of FSH in spermatogenesis is unclear as testosterone alone has been
      reported to be sufficient in the gonadotropin-deficient rat. This study examined
      the effects of recombinant FSH on the restoration of spermatogenesis after
      gonadotropin withdrawal by GnRH immunization. Adult Sprague-Dawley rats received
      GnRH immunogen (100 micrograms, sc, every 4 weeks) to induce gonadotropin
      deficiency, with severe spermatogenic regression occurring by 12 weeks.
      Recombinant human FSH was then given (10 or 50 IU/kg, sc, daily) for 7, 14, and
      21 days, with data from both dosages combined in the analyses. Testes were
      perfusion fixed, and germ cell numbers were quantified by the optical disector
      technique. After 7 days of FSH, testis weight significantly increased by 43% (P <
      0.01), with no further increases at 14 and 21 days. GnRH immunization severely
      reduced germ cell numbers, which were then significantly (P < 0.05) restored in
      all cell types, except elongated spermatids, by 7 days of FSH; type A
      spermatogonia (45%-->61% of control), type B spermatogonia/preleptotene
      spermatocytes (46%-->65%), leptotene/zygotene spermatocytes (39%-->55%),
      pachytene spermatocytes in stages I-VIII (11%-->30% control) and IX-XIV (4.3%-
      >22% control), and round spermatids in stages I-VIII (1.4%-->4.4% control).
      Prolonged FSH treatment did not further increase type A spermatogonial or
      pachytene spermatocyte number, whereas round spermatids increased to a peak of
      12.8% of the control value. At no stage did FSH increase elongated spermatid
      numbers above 1% of the control level. The incorporation of bromode-oxyuridine
      into spermatogonial and early spermatocyte nuclei did not change after GnRH
      immunization or FSH treatment. Sertoli cell number was not altered by any
      treatment; however, Sertoli cell nuclear volume was significantly decreased from
      the control value by GnRH immunization (142 +/- 9 vs. 455 +/- 22 microns 3; P <
      0.01) and increased after 7 and 14 days of FSH treatment to 212 +/- 10 and 259 +/
      24 microns 3, respectively. FSH treatment restored serum inhibin levels to
      normal, but did not increase serum or testicular androgen levels. We conclude
      that recombinant FSH partially restores spermatogenesis in the gonadotropin
      deficient rat by increasing the number of spermatogonia and promoting subsequent
      maturational steps up to the round spermatid stage. Spermatid elongation was not
      restored by FSH, indicating the need for an additional factor(s), most likely
      testosterone.

PMID- 7649113
TI  - Autofeedback suppression of growth hormone (GH) secretion in transgenic mice
      expressing a human GH reporter targeted by tyrosine hydroxylase 5'-flanking
      sequences to the hypothalamus.
AB  - Transgenic mice expressing a tyrosine hydroxylase-human (h) GH fusion gene in the
      hypothalamus exhibit a dwarf phenotype. The GH feedback mechanism(s) underlying
      the growth retardation in these animals was investigated by assessing peptide and
      messenger RNA (mRNA) levels of the hormones of the hypothalamic-GH-IGF-I axis.
      Pituitary GH content, hypothalamic GH-releasing hormone (GHRH) and somatostatin
      (SRIH) content, and serum IGF-I levels were measured by RIA. mRNA levels of
      hypothalamic GHRH and SRIH and of pituitary GH and the GHRH receptor were
      measured by Northern blot hybridization. Transgenic mice of both sexes and their
      wild-type littermates were studied at 2-4 months of age. The pituitary GH content
      was markedly reduced by 85% in male and by 87% in female transgenic mice compared
      to that in wild-type controls (P < 0.01 for both). The pituitary GH mRNA content
      was also decreased by 73% (P = 0.002) in transgenic male mice. Circulating IGF-I
      levels were significantly reduced by 66% and 68% in male and female transgenic
      mice, respectively (P = 0.001). The hypothalamic GHRH content was significantly
      reduced by 19% and 33% (P < 0.05) in male and female transgenic mice,
      respectively. No significant difference was detected, however, in the
      hypothalamic SRIH content between wild-type and transgenic mice. Hypothalamic
      GHRH mRNA levels were significantly decreased by 35% (P = 0.002) in transgenic
      male mice compared to those in wild-type littermates. In contrast, SRIH mRNA was
      not significantly changed. An even greater reduction (61%; P = 0.003) was
      observed in pituitary GHRH receptor mRNA in transgenic mice. These data indicate
      that the GH deficiency and dwarf phenotype of the tyrosine hydroxylase-hGH
      transgenic mouse can be attributed primarily to impaired hypothalamic GHRH
      production. The mechanism of GH feedback inhibition appears to involve direct
      suppression of GHRH gene expression by locally produced hGH in the hypothalamus.

PMID- 7649114
TI  - Production of interleukin-6 in human osteoblasts and human bone marrow stromal
      cells: evidence that induction by interleukin-1 and tumor necrosis factor-alpha
      is not regulated by ovarian steroids.
AB  - Studies in murine models of osteoporosis have suggested the hypothesis that
      ovarian steroids may control osteoclastic bone remodeling by limiting the
      production of interleukin-6 (IL-6) from osteoblasts and bone marrow stromal
      cells. To investigate this hypothesis in a human model, we have examined 12
      separate strains of normal human osteoblasts (HOB) and 11 separate strains of
      human bone marrow stromal cells (HBMSC) and determined whether ovarian steroids
      regulate the induction of IL-6 by interleukin-1 beta (IL-1 beta), tumor necrosis
      factor-alpha (TNF-alpha) or IL-1 + TNF. Treatment with IL-1, TNF or IL-1 + TNF
      resulted in the induction of IL-6 from both cell types with IL-1 + TNF inducing a
      synergistic induction of IL-6 in HOB (24- to 324-fold) and HBMSC (35-288 fold).
      Addition of 17 beta-estradiol or progesterone did not significantly alter IL-6
      messenger RNA or protein levels in either HOB or HBMSC cultures stimulated with
      IL-1, TNF or IL-1 + TNF. Cultures incubated up to 96 h with the steroids did not
      affect IL-6 expression. Furthermore ovarian steroids did not affect IL-6
      production in either HBMSC cultures representative of preosteoblasts or HOB
      cultures representative of highly differentiated osteoblasts. Specific
      chloramphenicol acetyl transferase assays and reverse transcriptase-polymerase
      chain reaction studies also demonstrated that the lack of an estrogen effect was
      not due to the failure of HOB to express functional estrogen receptors.
      Therefore, we conclude that the regulation of human osteoclastic bone remodeling
      by ovarian steroids does not occur through the direct regulation of IL-6 gene
      transcription or protein secretion in either early stages of osteoblast
      differentiation or the differentiated osteoblast.

PMID- 7649115
TI  - Effect of corticotropin-releasing factor on prostaglandin synthesis in
      endothelial cells and fibroblasts.
AB  - Recent evidence suggests that not only the end product of the hypothalamic
      pituitary-adrenal axis, but also other hormones in the axis may be involved in
      regulation of the inflammatory response. We investigated the role of CRF in the
      regulation of prostaglandin (PG) synthesis in fibroblasts and endothelial cells.
      Recombinant human interleukin-1 alpha (IL-1 alpha) increased prostacyclin
      synthesis in endothelial cells by 66% and prostaglandin E2 (PGE2) synthesis in
      fibroblasts by 91%. The PG response to IL-1 alpha was suppressed to about 50% by
      simultaneous addition of CRF in endothelial cells (75.6 +/- 6.2 vs. 159.7 +/-
      14.9 ng 6-keto-PGF1 alpha/mg protein) and fibroblasts (115.5 +/- 23 vs. 233.6 +/-
      42 ng PGE2/mg protein). IL-1 alpha enhanced phospholipase A2 activity by 30% and
      prostaglandin H synthase activity by 60%, and the two effects were completely
      blocked by CRF. It is concluded that CRF suppresses IL-1 alpha-induced PG
      synthesis through actions on both phospholipase A2 and cyclooxygenase. In view of
      the essential role of central PGE2 in IL-1 alpha-induced CRF/ACTH release, these
      findings suggest a novel regulatory cascade in immune-neuroendocrine
      interactions.

PMID- 7649116
TI  - Ovulatory cycle influences the stimulatory effect of stress on the expression of
      corticotropin-releasing factor receptor messenger ribonucleic acid in the
      paraventricular nucleus of the female rat hypothalamus.
AB  - The purpose of this study was to investigate whether the ovulatory cycle
      interferes with the effect of immobilization exposure on the expression of the
      type I CRF receptor (CRF-R) gene in the brains of female rats. The reproductive
      stages of adult female rats (200-250 g; 14 h of light; lights on at 0600 h) were
      verified by daily vaginal smears taken every morning for a minimum of three or
      four cycles before the experiment. Three hours after beginning the 90-min
      immobilization session, rats were deeply anesthetized and transcardially perfused
      with a solution of 4% paraformaldehyde in the morning (1100 h) and the afternoon
      (1700 h) of proestrus and diestrous day 2. Frozen brains were mounted on a
      microtome, cut in 30-microns slices, and processed for the detection of CRF-R
      messenger RNA (mRNA) by in situ hybridization histochemistry. Strand-specific
      antisense riboprobe was generated by in vitro transcription using T7 RNA
      polymerase and [35S]UTP. Basal levels of CRF-R transcripts were observed in
      several defined regions of the brain, such as the medial septal nucleus, nucleus
      of the diagonal band, basolateral and medial nuclei of the amygdala, red nucleus,
      pontine gray, and various layers of the cerebral cortex. Although control animals
      displayed almost undetectable levels of CRF-R mRNA in the paraventricular nucleus
      (PVN), immobilization stress induced a marked expression of the gene encoding CRF
      R in the dorsomedial parvocellular division of this hypothalamic structure in
      immobilized female rats. The large majority of CRF-R-positive cells were
      colocalized in CRF-immunoreactive neurons. Interestingly, stress-induced CRF-R
      transcription was significantly higher in the morning of proestrus than in the
      afternoon and on diestrous day 2. Apart from the PVN, none of the other sites
      exhibiting basal signals of CRF-R mRNA in the brain was affected by acute
      exposure to immobilization. These results provide evidence that neurogenic stress
      can stimulate the transcription of the type I CRF-R selectively in the
      parvocellular PVN, a phenomenon influenced by the neuroendocrine events
      regulating the reproductive cyclicity in female rats.

PMID- 7649117
TI  - Prolactin receptors and JAK2 in islets of Langerhans: an immunohistochemical
      analysis.
AB  - Lactogenic hormones, PRL and placental lactogen, are important regulators of
      insulin secretion and islet beta-cell proliferation. In this study we examined
      the presence of PRL receptor immunoreactivity in pancreatic islets of Langerhans
      using PRL receptor monoclonal antibodies provided by Dr. Paul Kelly. Studies were
      performed using islets isolated from neonatal, adult, and day 14 pregnant rats.
      The islets were examined by immunohistochemistry and laser scanning confocal
      microscopy. In neonatal rat islets, PRL receptors were observed in beta- and
      alpha-cells, but not in delta-cells. Among islet beta- and alpha-cells there was
      heterogeneity of cellular staining for PRL receptors. A small portion of the
      cells was intensely stained for PRL receptors. However, the majority of the cells
      had a much lower level of staining intensity, suggesting that most islet cells
      have a low level of PRL receptors. In general, alpha-cells were more uniformly
      stained than beta-cells. Similar results were obtained with adult rat islets, in
      which, again, there was a large range of staining intensity and many cells with
      low levels of PRL receptor. Rats on day 14 of pregnancy had an increased level of
      islet PRL receptor expression compared with age-matched control animals. There
      was also a decrease in cellular heterogeneity for PRL receptors, with nearly all
      cells having a uniformly high level of PRL receptor expression. JAK2, the
      tyrosine kinase associated with PRL receptors, was examined in Nb2 cells and
      islets. JAK2 immunoreactivity was detected at the cell membrane in very low
      levels in Nb2 cells. It was also found in numerous vesicular structures in the
      cytoplasm, where it colocalized with PRL receptors. A prominent feature of all
      cells was the presence of JAK2 in the nucleus, but not the nucleolus. In islets,
      JAK2 immunoreactivity was similarly observed in the nucleus of nearly all cells.
      However, the vesicular cytoplasmic location of JAK2 was less frequently observed
      and did not colocalize with PRL receptors. For comparison, JAK2 immunoreactivity
      was examined in several other tissues where it was detected in fibroblasts
      (endomysial and endoneurial cells), smooth muscle cells, and ganglion cells in
      the pancreas. JAK2 was notably absent from pancreas acinar cells, hepatocytes,
      skeletal muscle cells, and Schwann cells. This study demonstrates the presence of
      PRL receptors in islet beta- and alpha-cells, but not delta-cells. There was an
      increase in PRL receptor expression in islets during pregnancy, which is
      commensurate with the up-regulation of islet function. In addition, JAK2
      immunoreactivity was detected in most islet cells and Nb2 node cells.

PMID- 7649118
TI  - Expression of adrenomedullin in normal human lung and in pulmonary tumors.
AB  - Adrenomedullin (AM) is a potent hypotensive peptide recently discovered in
      extracts of human pheochromocytoma. In this report we present evidence, using
      reverse transcriptase-polymerase chain reaction, immunocytochemistry, and in situ
      reverse transcriptase-polymerase chain reaction, that AM is synthesized by
      several cell populations of the normal lung, tumor cell lines of pulmonary
      origin, and tumor specimens. Among the normal cell populations of the lung, we
      found AM expression in the columnar epithelium, some glands, neurons of the
      pulmonary parasympathetic nervous system, endothelial cells, chondrocytes,
      alveolar macrophages, and smooth muscle cells. In tumors, AM expression was
      located in most of the nonsmall cell lung carcinomas and in half of the small
      cell lung carcinomas studied. These findings suggest that AM may play a broad
      role in respiratory homeostasis and lung carcinogenesis.

PMID- 7649119
TI  - Ferritin heavy chain is a progesterone-inducible marker in the uterus during
      pregnancy.
AB  - The female sex steroid, progesterone, plays a central role in mammalian pregnancy
      by regulating crucial events in the uterus such as transformation of endometrium
      for implantation and maintenance of pregnancy. The hormone acts through its
      specific nuclear receptor and modulates the functions of target cells by
      controlling the synthesis of specific proteins. The identity of genes that are
      regulated by progesterone in the uterus during various phases of pregnancy,
      however, remains largely unknown. In this study, we employed a differential gene
      screening method to identify the gene encoding ferritin heavy chain (FHC), a
      component of the multisubunit iron-binding protein ferritin, as being regulated
      by progesterone in the uterus. We observed that uterine expression of the FHC
      messenger RNAs (mRNAs) rose dramatically at the onset of pregnancy, coincident
      with the surge of progesterone. FHC expression continued at this elevated level
      throughout gestation when the progesterone concentration remained high. At term,
      FHC expression declined sharply as the progesterone concentration dropped. We
      localized FHC proteins exclusively in uterine stromal cells, a major site of
      action of progesterone during pregnancy. Administration of mifepristone, an
      antiprogestin, during the early stages of pregnancy abolished both FHC mRNA and
      protein expression, clearly suggesting a primary role of progesterone in the
      regulation of this gene. Consistent with this scenario, administration of
      progesterone to ovariectomized animals after a brief estrogen priming led to a
      marked (25-fold) induction of FHC mRNA in the uterus, whereas estrogen,
      dexamethasone, or dihydrotestosterone had no effect. Based on these results, we
      propose that FHC is a novel and useful marker to study progesterone-regulated
      events in the uterus during pregnancy.

PMID- 7649120
TI  - Pituitary adenylate cyclase-activating peptide gene expression in corticotropin
      releasing factor-containing parvicellular neurons of the rat hypothalamic
      paraventricular nucleus is induced by colchicine, but not by adrenalectomy, acute
      osmotic, ether, or restraint stress.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) is a newly discovered
      neuropeptide that is present in high amounts in hypothalamic neuroendocrine
      neurons and potently stimulates the accumulation of cAMP within cells of the
      anterior pituitary. We have employed several specific antisera recognizing
      different parts of the PACAP precursor to elucidate the distribution of PACAP
      like immunoreactivities in the hypothalamic components of the hypothalamo
      pituitary-adrenocortical axis in sections obtained from normal and colchicine
      treated rats. Using immunohistochemistry with avidin-biotin-coupled peroxidase as
      a reporter system, high numbers of PACAP-immunoreactive perikarya were found in
      colchicine-pretreated rats in many of the parvicellular subdivisions of the
      hypothalamic paraventricular nucleus (PVN). A few cells were also found in the
      magnocellular subdivisions of the nucleus, and a similar small population of
      cells was observed in the dorsolateral aspect of the supraoptic nucleus. Using
      indirect immunofluorescence, the relation between CRF- and PACAP-containing
      neurons in the various parvicellular subnuclei of the PVN was studied, and a high
      degree of colocalization was demonstrated in the neurons of the medial
      parvicellular part of PVN. To further study the functional implications of PACAP
      in the hypothalamo-pituitary-adrenocortical axis, we examined the expression of
      PACAP messenger RNA (mRNA) in the PVN in response to five different stimulatory
      paradigms that previously have been shown to stimulate CRF mRNA expression in the
      medial parvicellular part of the PVN. The stimulatory challenges of
      adrenalectomy, restraint stress, ip injection of hypertonic saline, ether stress,
      and intracerebroventricular injection of colchicine induced significant
      elevations of CRF mRNA expression in the medial parvicellular part of the PVN. In
      contrast, the expression of PACAP mRNA, which is hardly detectable within the
      medial parvicellular part of the PVN, was induced only by colchicine treatment
      (from undetectable levels to 177 +/- 21 dpm/g; mean +/- SEM), whereas PACAP mRNA
      remained undetectable in this region of the PVN after exposure to any of the
      other stimulatory paradigms. The onset of colchicine-induced PACAP mRNA
      expression in the PVN was rapid (3 h), and PACAP mRNA levels remained elevated
      throughout the 48-h observation period. Considering the different topography and
      connections of the parvicellular subnuclei of the PVN, the current observations
      suggest that PACAP present in parvicellular neurons of the PVN may act not only
      as a neuroendocrine transmitter/modulator in the hypothalamo-pituitary
      adrenocortical axis, but also as transmitter mediating neurotransmission conveyed
      from the PVN to preganglionic neurons of the autonomic system.(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 7649121
TI  - Insulin receptor-related receptor messenger ribonucleic acid: quantitative
      distribution and localization to subpopulations of epithelial cells in stomach
      and kidney.
AB  - A novel member of the insulin receptor family, the insulin receptor-related
      receptor (IRR), was initially identified by cloning genomic DNA homologous to the
      insulin receptor. We have now used Northern blot and polymerase chain reaction
      analyses of a variety of human tissues to demonstrate that the kidney is a major
      site of IRR gene expression. IRR transcripts (approximately 6 and approximately 2
      kilobases) were detected only in human kidney by Northern blot analyses.
      Quantitative competitive polymerase chain reaction analysis revealed that IRR
      messenger RNA levels were distributed more widely. IRR transcripts in human
      kidney were approximately 3- to 10-fold greater than those in thymus, brain,
      heart, and stomach and approximately 150-fold higher than those in placenta,
      skeletal muscle, and liver. In situ hybridization histochemical analysis revealed
      that IRR transcripts were present in a subpopulation of cells within distal
      tubules of human kidney, beyond the most proximal segment of the distal
      convoluted tubule. In rat stomach, IRR messenger RNA was localized to a subset of
      neuroendocrine cells in gastric glands of the fundic mucosa. This selective
      distribution of IRR transcripts in human and rat tissues suggests that IRR may
      mediate the responses of a neuroendocrine factor involved in regulating select
      aspects of cell function in a highly tissue-specific manner.

PMID- 7649122
TI  - Immunohistochemical localization of thromboxane receptor and thromboxane synthase
      in rat testis.
AB  - The cellular localization of thromboxane A2 receptor (TXR) and thromboxane
      synthase (TXS) in rat testes was examined with an antibody against the carboxyl
      terminal tail of rat TXR and anti-porcine lung TXS antibody. By light microscopy
      immunoreactivity for TXR was shown to be present in spermatids, whereas
      spermatogonia, spermatocytes, and spermatozoa lacked the immunoreactivity.
      Immunoelectron microscopic analysis revealed that immunostainable TXR was present
      in acrosomes of spermatids. In contrast, immunoreactivity for TXS was present in
      all stages of spermatogenic cells; spermatogonia, spermatocytes, spermatids, and
      spermatozoa. TX system may possibly contribute to the formation of acrosomes or
      have some unrecognized functions in an autocrine/paracrine fashion.

PMID- 7649123
TI  - Differential gene expression of growth hormone (GH)-releasing hormone (GRH) and
      GRH receptor in various rat tissues.
AB  - Growth hormone (GH)-releasing hormone (GRH) acts on specific receptors in the
      anterior pituitary to stimulate the synthesis and release of GH. Recent reports
      suggest that GRH is also synthesized in extrahypothalamic tissues. To evaluate
      the potential roles of extrahypothalamic GRH, we studied the gene expression of
      GRH and GRH receptors in various rat tissues by reverse transcribed (RT)
      polymerase chain reaction (PCR). Total RNA was extracted from twenty-three rat
      organs and RT-PCR was performed with GRH and GRH receptor primers. Highly
      sensitive RT-PCR-Southern blotting showed that GRH and GRH receptor mRNA coexist
      in the widespread tissues (14 of 25 tissues). GRH mRNA was relatively abundant in
      the cerebral cortex, brain stem, testis, and placenta, while GRH receptor mRNA
      was abundant in renal medulla and renal pelvis. Northern blot hybridization using
      poly A+ RNA indicated that the transcript of GRH receptor gene found in the renal
      medulla was similar to the longer transcript (about 4 Kb) of pituitary GRH
      receptor in the size. These results suggest that GRH plays a potential role not
      only in the neuroendocrine axis, but also in the autocrine and paracrine systems
      in extrahypothalamic tissues.

PMID- 7649124
TI  - Wada memory disparities predict seizure laterality and postoperative seizure
      control.
AB  - We examined the efficacy of a memory difference score (DS: right minus left
      hemisphere memory) during the Wada test (intracarotid amobarbital procedure, IAP)
      for predicting seizure laterality and postoperative seizure outcome in 70 left
      speech dominant patients from two epilepsy centers. DS > or = 2, after addition
      of 1 point to the left hemisphere injection score to account for aphasia, were
      noted in 71.4% of patients and correctly predicted surgery side for 98.0% of
      these patients. The DS related significantly to seizure outcome at 1-year follow
      up (p < 0.002) and correctly predicted 80% of patients who were seizure-free.
      Patients whose DS did not correctly predict seizure laterality more frequently
      required invasive studies to establish seizure onset. The relationship of the DS
      to laterality did not differ significantly by class of IAP memory stimuli. When
      seizures originate from the temporal lobe, the IAP memory DS predicts seizure
      laterality by assessing the functional adequacy of the involved hemisphere and is
      predictive of seizure control.

PMID- 7649125
TI  - Intracarotid amobarbital procedure as a predictor of material-specific memory
      change after anterior temporal lobectomy.
AB  - Memory testing during the intracarotid amobarbital procedure (IAP) is used
      extensively to identify temporal lobe surgery candidates "at risk" for developing
      severe postoperative anterograde amnesia. However, the utility of the IAP in
      predicting commonly observed material-specific memory deficits has not been
      thoroughly investigated. We examined the utility of contralateral IAP memory
      testing, as an index of the functional capacity of the surgical temporal lobe, to
      predict postoperative material-specific memory changes on the Wechsler Memory
      Scale-Revised (WMS-R) in patients with left hemisphere speech dominance
      undergoing left (n = 32) and right (n = 31) temporal lobectomy (TL). Left TL
      patients who "passed" contralateral IAP memory testing (> or = 68% recognition of
      memory items) had significantly greater verbal memory decrements than those who
      "failed" the IAP, presumably as a result of removal of functional tissue. A
      similar relationship between contralateral IAP performance and visual memory
      performance was not observed among right TL patients. Thus, the functional
      adequacy of the tissue to be resected appears to be inversely related to
      postoperative verbal memory decrement, at least among left TL patients. This
      relationship is consistent with results of recent studies demonstrating an
      inverse relationship between verbal memory decrements after left TL and
      preoperative neuropsychological verbal memory performance, magnetic resonance
      imaging (MRI) hippocampal volumes, and degree of mesiotemporal sclerosis (MTS).

PMID- 7649126
TI  - Asymmetric and asynchronous infantile spasms.
AB  - Infantile spasms most commonly show symmetric behavioral and electroencephalogram
      (EEG) manifestations. Asymmetric and asynchronous behavioral spasms occur
      occasionally, but their relationship to ictal EEG and to other localizing studies
      has not received much attention. We reviewed 75 consecutive video-EEG recordings,
      done at UCLA from 1982 to 1992, that contained infantile spasms; 8,680 spasms
      were scored for behavioral and EEG asymmetry and asynchrony. Of the recorded
      spasms, 25% were asymmetric and 7% were asynchronous. Most asymmetric of
      asynchronous spasms were associated with an ictal EEG discharge that was
      contralateral to the behaviorally more involved side. In 12 of the 60 patients
      (20%), more than half of the recorded spasms were asymmetric of asynchronous.
      Baseline EEG, magnetic resonance imaging, positron emission tomography, and
      neurological examination revealed structural and functional brain abnormalities
      that involved the contralateral central region significantly more often in the
      children with > 50% spasm asymmetry or asynchrony than in the other children.
      Partial seizures with lateralized motor behavior also occurred frequently in
      these children. The findings suggest that asymmetric and asynchronous spasms are
      generated by a cortical epileptogenic region that involves the primary
      sensorimotor area. The combination of asymmetric and asynchronous infantile
      spasms, partial motor seizures involving the same side of the body, and pathology
      in the contralateral central region may represent a unique subset of symptomatic
      localization-related infantile epilepsy.

PMID- 7649127
TI  - Idiopathic photosensitive occipital lobe epilepsy.
AB  - We studied 10 neurologically normal patients (8 females, 2 males) aged 8-30 years
      (mean 17 years) who had recurrent episodes if visually induced occipital
      seizures. Television and computer screens were the main triggers. Seizure onset
      occurred between the ages of 5 and 17 years (mean 11 years). All seizures were
      stimulus related and began with elementary visual symptoms, followed in most
      patients by a slow clustering of cephalic pain, epigastric discomfort, and
      vomiting, with either normal of only mildly impaired responsiveness. EEG features
      included normal background activity, occipital spikes and waves, and a
      photoparoxysmal response which could be occipital, generalized, or both. Four
      patients also showed spontaneous generalized epileptiform abnormalities, and 3
      had rolandic spikes. An Oz electrode was critical in identifying epileptiform
      activity in some patients. Complete seizure control was achieved in most patients
      with monotherapy, although occasional stimulus-related seizures occurred in 3
      patients who showed a wider range of photosensitivity. These patients have an
      idiopathic localization-related epilepsy with age-related onset and specific mode
      of precipitation. Although this type of epilepsy has been reported previously, it
      has remained underrecognized, probably because it is difficult to differentiate
      clinically from migraine or from nonreflex childhood idiopathic occipital
      epilepsy.

PMID- 7649128
TI  - Intraoperative thermal inactivation of the hippocampus in an effort to prevent
      global amnesia after temporal lobectomy.
AB  - In an effort to assess the risk of amnesia after anterior temporal lobectomy
      (ATL), we conducted localized thermal inactivation (cooling) of the hippocampus
      with memory testing. Thirty-three ATL patients whose preoperative evaluation
      suggested risk for postoperative amnesia underwent hippocampal cooling. Cooling
      consisted of inserting a catheter in the temporal horn and irrigating it with an
      iced solution until a stable hippocampal temperature of approximately 20 degrees
      C was reached. Memory was assessed before and after cooling. In 12 of the 33
      patients, memory testing was either aborted or suggested poor contralateral
      support, and the hippocampus was resected in 2 of these patients. The remaining
      21 patients showed evidence of contralateral memory support, and the hippocampus
      was resected in 18. No patient became amnestic. These results suggest that
      intraoperative hippocampal cooling may be useful in selected cases. However, even
      among many patients who could cooperate with testing, discomfort, sedation,
      attentional deficits, confusion, and anxiety made test interpretation difficult.

PMID- 7649129
TI  - Fast spin-echo, magnetic resonance imaging-measured hippocampal volume:
      correlation with neuronal density in anterior temporal lobectomy patients.
AB  - To assess the value of magnetic resonance imaging (MRI)-measured hippocampal
      volume in the detection of hippocampal sclerosis, we studied 28 patients
      undergoing anterior temporal lobectomy for medically intractable mesial temporal
      lobe epilepsy. Hippocampal volumetry and visual analysis of T2 signal change were
      performed using fast spin-echo T2-weighed MRI. Quantitative neuronal density
      measurements were performed in the resected hippocampal specimens. There was a
      significant correlation between MRI-measured absolute hippocampal volume (AHV)
      and neuronal density in CA1, CA2, and CA3 subfields (p < 0.0001, p < 0.01, and p
      < 0.05, respectively). Differential hippocampal volume (side-to-side volume
      difference) failed to detect bilateral atrophy in three patients, but the
      bilateral hippocampal atrophy was recognized by considering AHV in these
      patients. This study suggests that MRI-measured AHV can be of value in elevating
      patients with mesial temporal lobe epilepsy, especially when there is no side-to
      side difference in hippocampal volumetry.

PMID- 7649130
TI  - Bilateral hippocampal atrophy in medial temporal lobe epilepsy.
AB  - Quantitative evidence of hippocampal atrophy has been correlated with site of
      seizure onset, hippocampal neuronal loss, and seizure relief after resection.
      Most studies have quantified hippocampal atrophy using ratios or differences
      between right and left hippocampal values. However, bilateral hippocampal atrophy
      may remain undetected by these techniques. To assess the frequency and
      implications of bilateral hippocampal atrophy, we studied absolute hippocampal
      volumes in 53 temporal lobectomy patients who had undergone intracranial
      electroencephalogram recordings preoperatively. Coronal images were constructed
      perpendicular to the longitudinal axis of the hippocampus. Atrophy was defined as
      > 2 SD below control values in the volume of the posterior 1.5 cm of the
      hippocampus. Five of 53 patients (9%) had bilateral hippocampal atrophy; four of
      these cases were undetected by ratios. Surgery was performed on the side of ictal
      onset in all five patients; four have been seizure-free for > 2 years. These
      results suggest that (a) mesial temporal sclerosis can be present bilaterally and
      may go undetected by hippocampal ratio or difference measures; (b) absolute
      hippocampal volume values as well as ratios are needed to detect all patients
      with bilateral hippocampal atrophy; and (c) temporal lobectomy is not
      contraindicated in patients with bilateral hippocampal atrophy, but success
      depends on electroencephalographic documentation of the side of predominant ictal
      onset.

PMID- 7649132
TI  - Search for the structures initiating seizures triggered by intraventricular
      injection of the mu opioid agonist dermorphin in rats.
AB  - Free-moving rats received intraventricular (i.c.v.) or intravenous (i.v.)
      injections of the mu opioid agonist dermorphin (DRM). The EEG activity of the
      cortex and of several structures near the injected lateral ventricle was
      recorded. The intravenous injections of DRM did not induce epileptiform activity.
      The intracerebroventricular injections of DRM triggered several types of
      electrical seizures and interictal spikes. With the aim of determining which
      structure gave rise to the epileptiform discharges, we compared the time
      relationships of epileptiform phenomena occurring in different structures.
      Epileptiform discharges, at once generalized, appeared first in the CA3 area of
      the ventral hippocampus, with involvement of the CA1 area of ventral hippocampus,
      the entorhinal cortex and the amygdala following immediately. We conclude that,
      after intracerebroventricular injection of a mu opiate agonist, epileptiform
      activity originates in the CA3 area of the ventral hippocampus.

PMID- 7649131
TI  - Alteration in levels of expression of brain calbindin D-28k and calretinin mRNA
      in genetically epilepsy-prone rats.
AB  - Variations in the concentration of free calcium in neurons is believed to play a
      major role in regulating neuronal excitability. Because calcium-binding proteins
      such as calbindin D-28k and calretinin help to regulate intracellular calcium, we
      investigated the possibility that the expression of these proteins may be
      affected in genetically epilepsy-prone rats (GEPRs). The mRNA levels of both
      proteins were compared across several brain regions using in situ hybridization
      histochemistry and Northern blot analysis with semiquantitation by optical
      density measures in autoradiograms from two GEPR strains that differ in the
      severity of audiogenic seizures (GEPR9 and GEPR3) and from Sprague-Dawley rats.
      Results revealed a lower level of expression in calbindin D-28k mRNA in the in
      the caudate putamen-accumbens nuclei in GEPR3 (-30%) and GEPR9 (-60%) relative to
      controls. The calbindin D-28k mRNA level was also lower in the reuniens nucleus
      of the thalamus (-41% in GEPR3; -34% in GEPR9). The calretinin mRNA level was
      lower in the substantia nigra compacta of both GEPR rat strains (-31% in GEPR3
      and -34% in GEPR9 relative to controls). No changes in mRNA were detected in
      other brain regions expressing calbindin D-28k or calretinin mRNA. These results
      indicate that the expression of these related calcium-binding proteins is altered
      in the GEPRs before the induction of seizures. This initial defect could alter
      either the calcium-buffering capacity or regulation of calcium-mediated processes
      by these proteins and thus play a role in the molecular cascade of events
      inducing the genetic susceptibility to, and the generalization of, seizures in
      these rat strains.

PMID- 7649133
TI  - Comparison of anticonvulsant efficacy of valproate during prolonged treatment
      with one and three daily doses or continuous ("controlled release")
      administration in a model of generalized seizures in rats.
AB  - Recently, sustained-release (SR) preparations of valproate (VPA) have been
      developed to minimize or prevent problems associated with plasma level
      fluctuations during therapy with conventional preparations. In the present
      experiments, the anticonvulsant activity of VPA was assessed during prolonged
      treatment with different administration protocols using the intravenous (i.v.)
      pentylenetetrazol (PTZ)-infusion seizure threshold model in rats. To simulate a
      controlled-release (CR) preparation, VPA was infused in a constant rate through
      chronically implanted intrajugular catheters in some of the experiments. In all
      experiments, the PTZ seizure threshold was repeatedly determined in individual
      rats with chronically implanted catheters at daily intervals. Injection of saline
      three times daily in a control group showed that the PTZ seizure threshold was
      stable throughout the experiment. Acute administration of VPA 200 mg/kg
      intraperitoneally (i.p.) significantly increased the seizure threshold. During
      prolonged treatment with three daily doses of 200 mg/kg i.p., anticonvulsant
      activity markedly increased on the second day of treatment and thereafter
      compared to the acute effect of VPA, although plasma levels measured at each
      seizure threshold determination did not differ significantly. This increase in
      anticonvulsant activity of VPA during prolonged treatment was much less
      pronounced with one instead of three daily doses. One daily intraperitoneal
      injection of VPA (200 mg/kg) plus continuous, constant-rate intravenous infusion
      of 400 mg/kg/day led to a marked increase in anticonvulsant activity similar to
      that in the experiment with three daily doses, indicating that not the peak
      levels but the duration of maintenance of active drug concentrations was
      important for development of enhanced anticonvulsant activity.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7649134
TI  - Effect of antiepileptic drugs on absence-like seizures in the tremor rat.
AB  - We examined the effects of conventional antiepileptic drugs (AEDs) on absence
      like seizures in homozygous tremor rats (tm/tm) to determine if they corresponded
      pharmacologically to human absence seizures and absence-like seizures in
      spontaneously epileptic rats (SER: zi/zi, tm/tm) with both tonic convulsive and
      absence-like seizures. Cortical and hippocampal EEG activity was recorded with
      chronically implanted electrodes. The effects of AEDS on seizures of the tremor
      rat showed profiles similar to those observed in human absence seizures and also
      in absence-like seizures of SER. The absence-like seizures, associated with
      paroxysmal bursts of 5-7-Hz spike-wave complexes, were inhibited by trimethadione
      (TMO 200 mg/kg intraperitoneally, i.p.), ethosuximide (ESM 100 and 200 mg/kg,
      i.p.), valproate (VPA 100 mg/kg, i.p.), and phenobarbital (PB 10 and 20 mg/kg,
      i.p.). Phenytoin (PHT 20 mg/kg, i.p.) was ineffective. These results are
      consistent with the conclusion that the tremor rat is a useful model for
      evaluating new AEDS for human absence seizures.

PMID- 7649135
TI  - Catatonia mimicking nonconvulsive status epilepticus.
AB  - Nonconvulsive status epilepticus (NCSE) and catatonia share many clinical
      features and distinguishing between them on the basis of the physical examination
      may be difficult and even impossible. Although several reports have been made of
      NCSE simulating catatonia, there are no published cases of catatonia mimicking
      NCSE. We report a 24-year-old woman whose initial examination was notable for a
      fixed stare, no response to voice or command, gaze preference, tonic head
      posturing, constant stereotypic chewing movements, profuse foamy salivation, and
      dramatic response to the parenteral administration of benzodiazepines (BZDs). She
      was initially misdiagnosed as having NCSE. EEG, however, was normal. We believe
      this is the first published report of catatonia simulating NCSE. The EEg may be
      more useful than the clinical examination in distinguishing NCSE from catatonia.

PMID- 7649136
TI  - Magnetic resonance imaging and spectroscopy findings after focal status
      epilepticus.
AB  - The etiology of cerebral abnormalities after focal status epilepticus (SE) is
      unknown. Possible causes include hypoxia and the excessive release of excitatory
      amino acids. Magnetic resonance imaging (MRI) of a 21-year-old patient with
      "cryptogenic" continuous motor seizures showed swelling and signal hyperintensity
      of the contralateral parietotemporal cortex, the thalamus, and the ipsilateral
      cerebellum on T2-weighted images. These regions are connected by glutamatergic
      pathways. Proton magnetic resonance spectroscopy (MRS) of the cortical lesion
      yielded a signal peak at the resonance frequency of 2.29 ppm, suggesting a focal
      increase of glutamate or its degradation product glutamine. At 3-month follow-up,
      structural alterations had disappeared, but the N-acetyl-aspartate/choline ratio
      was still reduced in the previously abnormal area. These findings are the first
      to demonstrate the contribution of MRS to pathophysiologic studies of focal SE in
      humans and, in combination with the pattern of imaging abnormalities, support a
      major role of glutamate for seizure-related brain damage.

PMID- 7649137
TI  - Alteration of regulatory enzyme activities in fast-twitch and slow-twitch muscles
      and muscle fibres in low-intensity endurance-trained rats.
AB  - The effect of progressive, low-intensity endurance training on regulatory enzyme
      activities in slow-twitch (ST) and fast-twitch (FT) muscle fibres was studied in
      32 rats. Of those rats 16 were trained on a treadmill at a running speed of 10
      m.min-1 5 days a week over an 8-week period. Running time was progressively
      increased from 15 min to 2 h.day-1. Of the rats 4 trained and 4 sedentary rats
      were also subjected to acute exhausting exercise. Enzyme activities of
      phosphofructokinase 1 (PFK1) from glycolysis, alpha-ketoglutarate dehydrogenase
      (alpha-KGDH) from the Krebs cycle and carnitine palmitoyltransferase (CPT I and
      II) from fatty acid metabolism in soleus, tibialis anterior and gastrocnemius
      muscles were measured in trained and sedentary rats. Enzyme activities of
      individual ST and FT fibres were measured from the freeze-dried gastrocnemius
      muscle of 8 trained and 8 sedentary rats. In the sedentary rats the activity of
      PFK1 in tibialis anterior and soleus muscles was 141% and 41% of the activity in
      gastrocnemius muscle, respectively. The activity of alpha-KGDH in tibialis
      anterior and soleus muscles was 164% and 278% of the activity in gastrocnemius
      muscle, respectively. The activity of CPT I in tibialis anterior and
      gastrocnemius muscles were at the same level, but in soleus muscle the activity
      was 127% of that in mixed muscle. Endurance training increased enzyme activities
      of alpha-KGDH and CPT I significantly (P < 0.05) in gastrocnemius muscle but not
      in soleus or tibialis anterior muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7649138
TI  - Measurement by laser-Doppler flowmetry of microcirculation in lower leg muscle at
      different blood fluxes in relation to electromyographically determined
      contraction and accumulated fatigue.
AB  - Single-fibre percutaneous laser-Doppler flowmetry (LDF) of the tibialis anterior
      muscle was performed continuously for measurement of the microcirculation during
      different blood fluxes, as well as in relation to different muscle activities and
      fatigue determined electromyographically (EMG). The laser-Doppler power spectrum
      density function was studied in a frequency range of 0-8.2 Hz as representing the
      blood flow most selectively. Reduced blood flow from tourniquet inflation caused
      a decrease in signal power density, compared to that of intact blood flow at
      rest. During postocclusion reactive hyperaemia an increased signal power was
      recorded. This reached its maximum within 4.4 (SD 1.88) s after deflation of the
      tourniquet. The different fluxes were recorded at high sensitivity and
      disturbances were small. Periods of 1-min static dorsi-flexion of the foot at 10,
      20, 30, 40, and 50% MVC (maximal voluntary contraction) with 1-min rest between
      were associated with a significant increase in LDF, the recordings obtained
      during the rest periods showing a tendency towards an increase. A decrease in the
      EMG mean power frequency (MPF) indicated accumulated fatigue. The LDF for the
      rest periods that followed upon continuous contractions up to the same MVC levels
      showed a tendency towards an increase but variability was large. With further
      development, these techniques may be useful in the evaluation of insufficiency of
      the peripheral circulation.

PMID- 7649139
TI  - Submaximal-exercise-induced impairment of human muscle to develop and maintain
      force at low frequencies of electrical stimulation.
AB  - The aim of this study was to test the hypothesis that low intensity exercise
      induced low frequency fatigue is caused by failure of excitation-contraction
      coupling. Changes in knee extension torque at 5, 10, 15, 20 and 50 Hz electrical
      stimulation of quadriceps muscle in ten healthy, young, male subjects were
      recorded during 20-min voluntary exercise followed by 60-min recovery. In seven
      of the ten subjects, changes in torque during 3 min of 10-Hz stimulation were
      recorded 2 min and 20 min after 20 min voluntary exercise. Exercise was performed
      at 30% of maximal voluntary contraction with a contraction plus relaxation period
      of 6 plus 4 s. Torque at 5, 10, 15, 20 and 50-Hz stimulation at the end of
      exercise was reduced to mean 91.0 (SEM 5.4)%, 68.7 (SEM 5.4)%, 67.2 (SEM 3.9)%,
      66.5 (SEM 4.5)% and 74.7 (SEM 4.3)% of control values, respectively. During the
      first 30 s of the 3 min 10-Hz stimulation, torque was reduced in exercised muscle
      and increased in nonfatigued muscle. The reduction in torque was more marked 20
      min after exercise than after 2 min. In conclusion, the pattern of depression and
      recovery of muscle force observed was in agreement with the hypothesis that the
      main cause of low intensity exercise-induced low frequency fatigue is an
      impairment of excitation-contraction coupling.

PMID- 7649140
TI  - Muscle metabolism during exercise using phosphorus-31 nuclear magnetic resonance
      spectroscopy in adolescents.
AB  - Very little has been reported on muscle energetics during exercise in
      adolescents. This is attributable to the difficulty of subjecting children to
      muscle biopsy. The purpose of this study was to investigate the characteristics
      of muscle metabolism during exercise in vivo in adolescents by comparing firstly,
      with adults and secondly, the differences resulting from physical activity using
      phosphorus-31 nuclear magnetic resonance (31P NMR) spectroscopy. The subjects
      were boys aged 12 to 15 years, comprising 21 trained boys and 23 control boys,
      and 6 adults controls. The ratio of phosphocreatine (PCr):(PCr + P(i)), where
      P(i) is inorganic phosphate intracellular pH at exhaustion and the time constant
      of PCr during recovery were measured in all the subjects using 31P NMR. Both
      groups of children showed higher values of PCr:(PCr + P(i)) and intracellular pH
      at exhaustion than did the adult control group (P < 0.01 or P < 0.05). However,
      no significant differences were found between the trained boys and the control
      boys with respect to PCr:(PCr + P(i)) and intracellular pH at exhaustion. On the
      other hand, we found the same values for PCr time constant in all groups. This
      result suggested no differences of the muscle oxidative capacity between children
      and adults. We concluded that the adolescents, aged 12 to 15 years in both the
      trained and control groups, had less glycolytic ability during exercise than the
      adults.

PMID- 7649141
TI  - Cross-correlation of bilateral differences in fatigue during sustained maximal
      voluntary contraction.
AB  - Maximal isometric force and electromyograph (EMG) activity of biceps brachii
      muscle during bilateral sustained elbow flexion were followed in 25 right-handed
      oarsmen. The percentage decline in force was greater for the left than for the
      right arm. Also, the mean power frequency (MPF) and the root mean square (rms)
      value of the EMG amplitude decreased more for the left than for the right arm. It
      was hypothesized that a "common drive" would indicate that the two forces curves
      would be highly correlated during the nonfatigued period, but the level of cross
      correlation would decline during muscle fatigue. For the first 4 s of the
      contraction, the cross-correlation between the right and left force was high (r =
      0.99), but thereafter it declined rapidly to a constant level. The decline of the
      cross-correlation was accompanied by a similar decrease in the correlation
      between the right and left EMG activations (MPF and rms). Thus, the decline in
      the cross-correlation level of force accompanied by a similar decrease in the
      correlation level of EMG would suggest a fatigue-induced neural derangement of
      the common drive.

PMID- 7649143
TI  - Comparison of two cool vests on heat-strain reduction while wearing a
      firefighting ensemble.
AB  - This study evaluated the effectiveness of a six-pack versus a four-pack cool vest
      in reducing heat strain in men dressed in firefighting ensemble, while resting
      and exercising in a warm/humid environment [34.4 degrees C (day bulb), 28.9
      degrees C (wet bulb)]. Male volunteers (n = 12) were monitored for rectal
      temperature (Tre), mean skin temperature (Tsk), heart rate, and energy
      expenditure during three test trials: control (no cool vest), four-pack vest, and
      six-pack vest. The cool vests were worn under the firefighting ensemble and over
      Navy dungarees. The protocol consisted of two cycles of 30 min seated rest and 30
      min walking on a motorized treadmill (1.12 m.s-1, 0% grade). Tolerance time for
      the control trial (93 min) was significantly less than both vest trials (120
      min). Throughout heat exposure, energy expenditure varied during rest and
      exercise, but no differences existed among all trials (P > 0.05). During the
      first 60 min of heat exposure, physiological responses were similar for the four
      pack and six-pack vests. However, during the second 60 min of heat exposure the
      six-pack vest had a greater impact on reducing heat strain than the four-pack
      vest. Peak Tre and Tsk at the end of heat exposure for 6-pack vest [mean (SD)
      38.0(0.3) degrees C and 36.8(0.7) degrees C] were significantly lower compared to
      four-pack [38.6(0.4) degrees C and 38.1(0.5) degrees C] and controls [38.9(0.5)
      degrees C and 38.4(0.5) degrees C].(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7649142
TI  - Modulation of the human nociceptive reflex by cyclic movements.
AB  - During static conditions the nociceptive reflex is known to vary as a function
      of, for example, the stimulus position, stimulus intensity, and muscle
      contraction. The aim of the present human study was to investigate whether the
      reflex and the corresponding perception of pain are modulated by cyclic movements
      of the limb involved. Reflexes, evoked by nociceptive electric stimulation of the
      sural nerve, were recorded from the biceps femoris and the rectus femoris muscles
      in eight volunteers. Four different experiments were performed to compare the
      nociceptive reflex and pain score elicited during active isometric/dynamic
      flexion/extension of the knee joint. The amplitudes of the reflexes were largest
      for the dynamic conditions. The reflexes, evoked during dynamic extension and
      isometric contraction of the rectus femoris muscle, had the shortest latencies
      but the recordings from the biceps femoris muscle were larger than from the
      rectus femoris muscle. Knee joint angle recordings showed that the largest angle
      variations occurred for the dynamic conditions and were only marginally disturbed
      for the isometric conditions. A given stimulus intensity evoked the highest pain
      intensity during isometric contractions. This indicates that there would seem to
      be no causal relationship between the size of the nociceptive reflex and the pain
      intensity.

PMID- 7649144
TI  - The influence of the intensity of treadmill walking upon changes in lipid and
      lipoprotein variables in healthy adults.
AB  - The purpose of the present study was to compare the acute and delayed effects of
      low- and moderate-intensity exercise on serum lipoprotein concentrations. Twelve
      healthy volunteers (five men, seven women), aged 28 (2) years [mean (SEM)],
      maximal oxygen uptake (VO2max) 48 (3) ml.kg-1.min-1 walked on a treadmill for 90
      min, on two separate occasions, in a balanced design. On one occasion walking was
      at a grade which elicited 32.1 (0.8)% of VO2max, i.e. low intensity, while on the
      other it elicited 60.1 (1.6)% of VO2max, i.e. moderate intensity (MI). Serum
      concentrations of total cholesterol (TC), triacylglycerol (TAG), high density
      lipoprotein cholesterol (HDL-C) and the subfraction HDL2-C free fatty acids (FFA)
      and free glycerol were measured in venous blood samples drawn before exercise
      (after a 12-h fast), during walking and after 1 h and 24 h of recovery. Serum TAG
      concentrations decreased as a result of the exercise bout over the period of
      observation (P < 0.05), but this decrease was not different between the two
      intensities. Changes in serum TC concentrations over time differed between trials
      (P < 0.05). Serum free glycerol and FFA concentrations increased during exercise
      bouts, these increases being (P < 0.05) greater with MI. The decrease in serum
      TAG concentrations during and after a single episode of either prolonged low or
      moderate intensity exercise may be associated with an increased clearance and/or
      a decreased secretion of TAG-rich lipoproteins.

PMID- 7649145
TI  - Effects of unilateral isometric strength training on joint angle specificity and
      cross-training.
AB  - The purpose of this study was to examine the effects of unilateral isometric leg
      extension strength training on the strength and integrated electromyogram (IEMG)
      of both the trained and untrained limbs at multiple joint angles. A training
      (TRN) group [nine women; mean (SD) age, 20(1) years] exercised for 6 weeks with
      isometric leg extensions at 80% of maximal isometric torque. A control (CTL)
      group [eight women; 21(1) years] did not exercise. The training was performed
      three times per week on a Cybex II isokinetic dynamometer at a joint angle where
      the lever arm was 0.79 rad below the horizontal plane. The subjects were tested
      pre- and posttraining for maximal unilateral isometric torque in both limbs at
      joint angles of zero, 0.26, 0.79, 1.31, and 1.57 rad below the horizontal plane.
      Bipolar surface electrodes were used to record the IEMG of the vastus lateralis
      (VL) and vastus medialis (VM) during the isometric tests. Three univariate
      (torque, IEMG-VL, and IEMG-VM) four-way (group x time x limb x angle) mixed
      factorial ANOVAs were used to analyze the data. The results indicated joint angle
      specificity for isometric torque in the TRN group only, with significant
      increases in torque at 0.79 (P = 0.0004) and 1.31 (P = 0.0039) rad. No
      significant increases in torque were found in the untrained limb of the TRN group
      or in either limb of the CTL group. Similarly, there were no significant changes
      in IEMG as a result of the training for the VL or VM.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7649146
TI  - Contractile properties of the human triceps surae muscle during simulated
      weightlessness.
AB  - The effect of a 120-day period of bed rest on the mechanical properties of human
      triceps surae muscle was studied in a group of male volunteers (n = 6, mean age
      38 years). The results shows that the contractile properties of skeletal muscle
      in response to disuse change considerably. Time to isometric peak tension of the
      triceps surae muscle increased from 120 (SEM 3.0)ms to 136 (SEM 2.9)ms (P <
      0.01), half relaxation time from 92 (SEM 2.1)ms to 100 (SEM 1.6)ms (P < 0.05) and
      total contraction time from 440 (SEM 9.9)ms to 540 (SEM 18.7)ms (P < 0.001).
      Isometric twitch force (Ft) decreased by a mean of 36.7% (P < 0.05), maximal
      voluntary contraction (MVC) and maximal force (Fmax) by a mean of 45.5% and
      33.7%, respectively (P < 0.05-0.01). The value Fmax:Ft ratio increased by 3.6%
      (nonsignificant). The difference between Fmax and MVC, expressed as a percentage
      of Fmax and referred to as force deficiency, has also been calculated. Force
      deficit increased by a mean of 60% (P < 0.001) after bed rest. Force-velocity
      properties of the triceps surae muscle calculated according to an absolute scale
      of voluntary and electrically evoked contraction development decreased
      considerably. The calculations of the same properties on a relative scale did not
      differ substantially from the initial physiological state. The results would
      suggest that muscle disuse is associated with both atrophy and a reduction in
      contractility in the development of Fmax and decreased central (motor) drive. The
      change in the triceps surae muscle contractile velocity properties may indicate
      changes in the kinetically active state in the muscles.

PMID- 7649147
TI  - The oxygen uptake-power regression in cyclists and untrained men: implications
      for the accumulated oxygen deficit.
AB  - The regression of oxygen uptake (VO2) on power output and the O2 demand predicted
      for suprapeak oxygen uptake (VO2peak) exercise (power output = 432 W) were
      compared in ten male cyclists [C, mean VO2peak = 67.9 (SD 4.2) ml.kg-1.min-1] and
      nine active, yet untrained men [UT, mean VO2peak = 54.1 (SD 6.5) ml.kg-1.min-1].
      The VO2-power regression was determined using a continuous incremental cycle test
      (CON4), performed twice, which comprised several 4-min exercise periods
      progressing in intensity from approximately 40%-85% VO2peak. Minute ventilation
      (VE), heart rate (HR), respiratory exchange ratio (R), blood lactate
      concentration ([la-]b) and rectal temperature (Tre) were measured at rest and
      during CON4. The slope of the VO2-power regression was greater (P < or = 0.05) in
      C [12.4 (SD 0.7) ml.min-1.W-1] compared to UT [11.7 (SD 0.4) ml.min-1.W-1]; as a
      result, the O2 demand (at 432 W) was also higher (P < or = 0.05) in C [5.97 (SD
      0.23) l.min-1] than UT [5.70 (SD 0.15) l.min-1]. Exercise R and [la-]b were lower
      (P < or = 0.05) in C in comparison to UT at all power outputs, whereas VE and HR
      were relatively lower (P < or = 0.05) in C at power outputs approximating 180 W,
      220 W and 270 W. Differences in fat metabolism estimated over the first three
      power outputs accounted for approximately 19% of the difference in VO2-power
      slopes between the groups and up to 46% of the difference in VO2 at a given
      intensity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7649148
TI  - Change in the peripheral CO2 chemoreflex from rest to exercise.
AB  - A single-breath CO2 test of peripheral chemosensitivity has recently been
      described, and elaborated based on model simulations. This study was designed to
      measure the peripheral CO2 chemoreflex at rest and during heavy exercise to see
      if carotid chemosensitivity to CO2 increased. Ten healthy, adult males performed
      an incremental exercise test to determine their ventilatory anaerobic threshold
      (VAT), and 20 minutes of steady-state exercise at a pre-determined power output
      above VAT. Arterialized venous blood was obtained during each minute of
      incremental exercise to verify development of metabolic acidosis. Carotid
      chemosensitivity was tested repeatedly at rest and in steady-state exercise by
      the ventilatory response to a single breath of 13% CO2 in air. The peripheral
      chemoreflex for CO2 for the group of subjects doubled from rest to exercise (mean
      0.096 l.s-1.kPa-1) with all subjects showing an increase. We conclude that the
      gain of the carotid CO2 chemoreflex increases from rest to exercise at work above
      the VAT.

PMID- 7649150
TI  - Mechanisms of nuclear signalling by vitamin D3. Interplay with retinoid and
      thyroid hormone signalling.
AB  - Hormones that act through nuclear receptors contribute to vertebrate development
      and homeostasis by serving as biological signals to control cellular growth and
      differentiation. Their response pathways must meet two requirements, which can be
      contradictory: they must be highly specific for a given signal, but at the same
      time they have to be flexible, allowing different responses under different
      physiological conditions. The current model for nuclear signalling of vitamin D3
      (calcitriol), thyroid hormone and retinoic acid seems to be too simple to solve
      the specificity puzzle. Therefore, an advanced model is proposed that combines
      recent findings on the structure of hormone response elements, the promiscuous
      dimerization of the receptors for vitamin D3, thyroid hormone and retinoids and
      the heterodimer polarity. Special attention is taken on the mechanism of vitamin
      D3 signalling, where at least 14 different pathways are differentiated.

PMID- 7649149
TI  - Effects of specific versus cross-training on running performance.
AB  - The cross-training (XT) hypothesis suggests that despite the principle of
      specificity of training, athletes may improve performance in one mode of exercise
      by training using another mode. To test this hypothesis we studied 30 well
      trained individuals (10 men, 20 women) in a randomized longitudinal trail.
      Subjects were evaluated before and after 8 weeks of enhanced training
      (+10%/week), accomplished by adding either running (R) or swimming (XT) to
      baseline running, versus continued baseline running (C). Both R (-26.4s) and XT (
      13.2s) improved time trial (3.2 km) performance, whereas C did not (-5.4s). There
      were no significant changes during treadmill running in maximum oxygen uptake
      (VO2peak; -0.2, -6.0, and +2.7%), steady state submaximal VO2 at 2.68 m.s-1 (
      1.2, -3.3 and +0.2 ml.kg-1.min-1), velocity at VO2peak (+0.05, +0.25 and +0.09
      m.s-1) or accumulated O2 deficit (+11.2, -6.1 and +9.4%) in the R, XT or C
      groups, respectively. There was a significant increase in velocity associated
      with a blood lactate concentration of 4 mmol.l-1 in R but not in XT or C (+0.32,
      +0.07 and +0.08 m.s-1). There were significant changes in arm crank VO2peak (+5%)
      and arm crank VO2 at 4 mmol.l-1 (+6.4%) in XT. There was no significant changes
      in arm crank VO2peak (+1.3 and -7.7%) or arm crank VO2 at 4 mmol.l-1 (+0.8 and
      +0.4%) in R or C, respectively. The data suggest that muscularly non-similar XT
      may contribute to improved running performance but not to the same degree as
      increased specific training.

PMID- 7649151
TI  - Evidence for a catalytic role of tyrosine 383 in the peptidase reaction of
      leukotriene A4 hydrolase.
AB  - Leukotriene A4 (LTA4) hydrolase is a bifunctional zinc metalloenzyme which
      catalyzes the final step in the biosynthesis of the proinflammatory leukotriene
      B4 and which also possesses a peptidase activity. From sequence comparisons with
      aminopeptidases, a tyrosine at position 383 in LTA4 hydrolase has been suggested
      as a possible catalytic amino acid. To explore the potential role of this amino
      acid in catalysis, we replaced the tyrosine residue with phenylalanine, histidine
      or glutamine residues by site-directed mutagenesis. The mutated cDNAs were
      expressed in Escherichia coli and the resulting recombinant proteins, named
      [Y383F]LTA4 hydrolase, [Y383H]LTA4 hydrolase and [Y383Q]LTA4 hydrolase, were
      purified to homogeneity to allow assays of both the epoxide hydrolase activity,
      i.e. the conversion of LTA4 into leukotriene B4, and the peptidase activity. None
      of the mutated proteins exhibited significant peptidase activities, all of them
      showing activities less than 0.3% that of the wild-type enzyme. The epoxide
      hydrolase activity was not affected to the same degree and corresponded to 11, 16
      and 17% that of the unmutated enzyme for [Y383F]LTA4 hydrolase, [Y383H]LTA4
      hydrolase and [Y383Q]LTA4 hydrolase, respectively. Kinetic analysis was performed
      with the mutant [Y383Q]LTA4 hydrolase, which revealed an approximately 10-fold
      increase in Km for leukotriene A4 compared to that for the unmutated enzyme. At
      high concentrations of substrate, the difference in enzyme velocity was only
      moderate, with Vmax values of 600 nmol.mg-1.min-1 and 1000 nmol.mg-1.min-1 for
      [Y383Q]LTA4 hydrolase and the wild-type enzyme, respectively. No such effect of
      substrate concentration could be observed on the peptidase activity. As a
      positive control, we exchanged a glycine residue in position 386 for an alanine
      residue, and the recombinant protein, [G386A]LTA4 hydrolase retained 19% and 77%
      of the peptidase and epoxide hydrolase activities, respectively. The results from
      this study are consistent with a role for Tyr383 in the peptidase reaction of
      LTA4 hydrolase, where it may act as a proton donor in a general base mechanism.
      However, our data do not allow a similar interpretation for the mechanism
      involved in the hydrolysis of LTA4 into LTB4.

PMID- 7649152
TI  - Selection and characterization of mammalian cell lines with stable over
      expression of human pituitary receptors for gonadoliberin.
AB  - The cDNA encoding the receptor for gonadoliberin (GnRH or LH-RH) was isolated
      from a human pituitary cDNA library and heterologously expressed in the murine
      fibroblast cell line LTK-. By using a dicistronic expression strategy utilizing
      the internal ribosomal-entry-site sequence of poliovirus, single cell clones with
      stable and high expression of human gonadoliberin receptors were selected. In
      radioligand saturation-binding experiments, the gonadoliberin antagonist
      Cetrorelix showed high-affinity binding to the heterologously expressed human
      gonadoliberin receptor with a Kd of 0.1 nM. The pharmacological profile using
      125I-Cetrorelix as radioligand and the authentic gonadoliberin or agonistic and
      antagonistic derivatives as competitors, showed a distinct rank order of binding
      potencies. Superagonistic gonadoliberin derivatives had more than ten-times
      higher binding affinities in comparison to gonadoliberin with a Kd of 3.47 nM.
      The gonadoliberin receptor expressed in stably transfected LTK- cells coupled to
      the inositol phosphate signal-transduction pathway. Gonadoliberin stimulated the
      synthesis of inositol 1,4,5-trisphosphate in a dose-dependent way with an EC50 of
      5 nM. This stimulatory effect of gonadoliberin was completely antagonized by
      Cetrorelix in equimolar concentrations, demonstrating the high potency of this
      competitive receptor antagonist. In growth-arrested cells, a transient expression
      of the c-fos protooncogene was induced by gonadoliberin or [D-Trp6]gonadoliberin,
      showing that the gonadoliberin receptor couples to a putative mitogenic signal
      transduction pathway in this heterologous cell system.

PMID- 7649153
TI  - Recombinant and chemical derivatives of apamin. Implication of post
      transcriptional C-terminal amidation of apamin in biological activity.
AB  - The use of the colicin A lysis protein to direct the extracellular release of a
      fusion protein from Escherichia coli was investigated as an approach for the
      preparation of recombinant animal toxins. Apamin, a bee venom neurotoxin, was
      used as the model toxin. It is reticulated by two disulfide bridges and interacts
      with small conductance Ca(2+)-activated K+ channels. Substantial amounts of free
      recombinant apamin were obtained by CNBr cleavage of the fusion protein [col-(1
      171)-apa] and HPLC purification. It was recognized by conformation-dependent
      monoclonal antibodies with a K0.5 value close to that for natural apamin,
      indicating that folding was correct. In toxicity and binding experiments, the
      recombinant apamin displayed low activity. The recombinant and natural molecules
      differed by the amidation of the C-terminal histidine residue. Previous
      structure/activity relationship studies do not implicate this C-terminal residue
      in activity but the role of its amidation was not investigated. An apamin analog
      with a non-amidated C-terminal residue was then chemically synthesized. The
      biological properties of both recombinant and chemical molecules were determined.
      Amidation of the C-terminal alpha-carboxyl of apamin appears to be essential for
      full expression of its biological activity.

PMID- 7649154
TI  - Structural properties of recombinant domain III-3 of perlecan containing a
      globular domain inserted into an epidermal-growth-factor-like motif.
AB  - A fragment comprising approximately domain III-3 of the basement membrane heparan
      sulfate proteoglycan perlecan was prepared in recombinant form from kidney cell
      clones. This fragment was predicted to contain a cysteine-free globular domain
      inserted within an epidermal-growth-factor(EGF)-like motif (L4 module) and three
      additional EGF-like motifs (LE module) without large inserts. This prediction was
      confirmed by electron microscopy, which demonstrated a globule joined to a very
      short rod-like segment. The globule was selectively destroyed by pepsin, which
      also demonstrated that its insertion into an EGF-like motif did not prevent the
      typical disulfide connections known for such motifs. Yet the globule was more
      stable against neutral proteinases. The fragment showed a distinct content (55
      60%) of alpha helical and beta structure and a partially reversible melting of
      the conformation in 6 M guanidine. Antibodies raised against recombinant domain
      III-3 demonstrated a complete cross-reaction with tissue-derived perlecan but not
      with laminin and a distinct basement membrane staining of tissue sections. Most
      of the epitopes were lost after reduction and alkylation. Together the data
      demonstrated a proper folding of recombinant domain III-3 similar to its
      structure in the native protein and provided the first structural evidence for a
      novel globular protein motif L4 based on an EGF-like scaffold.

PMID- 7649155
TI  - Prolonged half-life in the circulation of a chemical conjugate between a pro
      urokinase derivative and human serum albumin.
AB  - Pro-urokinase is a natural plasminogen activator that displays a clot-lysis
      activity through a fibrin-dependent mechanism. It seems to be a promising agent
      for the treatment of coronary thrombosis. Like tissue-type plasminogen activator
      and two-chain urokinase-type plasminogen activator, pro-urokinase has a very
      short half-life in circulation. It has been described that conjugation of serum
      albumin with pro-urokinase in plasma may occur that could protect this protein
      from degradation. In this study we describe the insertion of an extra cysteine
      residue in the N-terminal end of des-(C11-K135)-pro-urokinase (delta 125-proUK),
      a pro-urokinase deletion mutant lacking amino acids 11-135. We have expressed and
      purified the new mutein [H5K, S9C, N10T] des-(C11-K135)-pro-urokinase (Cys-delta
      125-pro-urokinase) and chemically conjugated it with serum albumin via the extra
      cysteine of Cys-delta-pro-urokinase. The purified conjugate obtained has a lower
      specific amidolytic activity (72,000 U/mg) than unconjugated Cys-delta 125-pro
      urikinase (240,000 U/mg) due to its higher molecular mass and has a similar
      fibrinolytic activity in a clot lysis test to that of delta 125-pro-urokinase. We
      established an ELISA to measure the concentration of the conjugate in plasma and
      to follow the pharmacokinetics of the conjugate in monkeys after bolus injection.
      The conjugate displays significant lysis of human plasma clots in vivo and a
      dramatic increase of the half-life in the circulation, with respect to pro
      urokinase and delta 125-pro-urokinase. Therefore, preliminary biological
      characterisation of this conjugate indicates that it could be a good candidate to
      inject as a bolus, compared with the infusion regimen needed with pro-urokinase.

PMID- 7649156
TI  - Top-down control analysis of systems with more than one common intermediate.
AB  - The analysis of the control of complex metabolic systems can be greatly
      simplified by application of the top-down approach of metabolic control analysis,
      in which the reactions of the system are grouped together into a small number of
      blocks connected by a common intermediate. The experimental application of the
      top-down approach has so far been limited to systems that have only a single
      intermediate. In this study, we demonstrate that the connectivity and summation
      theorems of metabolic control analysis hold with any number of intermediates
      between the metabolic blocks, and in doing so show that top-down analysis is
      valid for systems with multiple intermediates and so can be applied to most
      metabolic systems regardless of their complexity; an example of such an
      application is provided. Top-down control analysis has successfully described the
      control of mitochondrial respiration by dividing the system into three blocks,
      the respiratory chain, phosphorylation system and proton leak, all linked by a
      single intermediate, proton motive force. Here, we subdivide the respiratory
      chain into succinate consumers and cytochrome oxidase so that a second
      intermediate, cytochrome c redox state, is generated. Despite the fact that the
      redox state of cytochrome c is not measured, we solve the control over the system
      fluxes. In common with previous studies, we find that under conditions where
      there is no ATP turnover (state 4), respiration is largely controlled by proton
      leak, while at maximal ATP turnover (state 3) respiration is controlled by the
      respiratory chain and the phosphorylating system. In state 4,85% of the control
      by the respiratory chain resides with cytochrome oxidase. As ATP turnover
      increases, the respiration rate increases, and the control by the respiratory
      chain shifts from cytochrome oxidase to the succinate consumers, so that in state
      3 83% of the control by the respiratory chain lies in the reactions between
      succinate and cytochrome c and only 17% resides with cytochrome oxidase.

PMID- 7649157
TI  - Concerning the measurement of flux control coefficients by enzyme titration.
      Steady states, quasi-steady-states, and the role of time in control analytical
      experiments.
AB  - An established method to determine flux control coefficients is the enzyme
      titration method in which the change in pathway flux upon a change in the enzyme
      concentration is measured. In this study, the application of this method to a
      simple reconstituted pathway was investigated by simulated measurements. The
      pathway was assumed to be in the quasi-steady-state, which is the experimental
      realization of the mathematical construct 'steady state'. It was shown that flux
      control coefficients, calculated in a way that mimics their experimental
      determination, were strongly time dependent. Initially, the calculated flux
      control coefficient was high for the enzyme adjacent to the reaction monitoring
      the flux, and the steady-state value was overestimated. Likewise, flux control
      coefficients were underestimated for enzymes further away from the monitoring
      reaction. The observed time course of simulated flux control coefficients was
      shown to reflect the fact that experimental systems are not steady state but
      quasi-steady-state. For a pathway in the quasi-steady-state, some of the problems
      with enzyme titration experiments can be overcome by allowing the system to relax
      for a time interval that is large compared with the turnover time of the pooled
      pathway intermediates.

PMID- 7649158
TI  - Epidermal growth factor (EGF) induces serine phosphorylation-dependent activation
      and calcium-dependent translocation of the cytosolic phospholipase A2.
AB  - Phospholipase A2 (PLA2) is a key enzyme in the release of arachidonic acid and
      subsequent production of eicosanoids, which play an important role in a variety
      of biological processes, including mitogenic signalling by epidermal growth
      factor (EGF). In a previous study [Spaargaren, M. et al. (1992) Biochem J. 287,
      37-43] we identified the EGF-activated PLA2 as being similar to the recently
      cloned high-molecular-mass cytosolic phospholipase A2 (cPLA2). In the present
      study we demonstrate a rapid transient EGF-induced activation of this cPLA2 and
      an EGF-induced increase in phosphorylation of the cPLA2. The EGF-induced
      activation of cPLA2 is reversed upon phosphatase treatment showing
      phosphorylation-dependent activation of the cPLA2. No direct association of the
      cPLA2 to the EGF receptor was detected under conditions where such an association
      with phospholipase C-gamma was demonstrated. Phosphoamino acid analysis of this
      cPLA2 showed that EGF induced an increase in serine phosphorylation exclusively,
      no tyrosine phosphorylation being observed. EGF treatment of the cells resulted
      in a Ca(2+)-dependent translocation of the cPLA2 from the cytosol to the membrane
      fraction. This is due to an EGF-induced [Ca2+]i rise which is dependent on the
      influx of extracellular Ca2+ via voltage-independent Ca2+ channels. It is shown
      that the Ca(2+)-dependent association of cPLA2 to membranes does not require
      accessory membrane molecules.

PMID- 7649159
TI  - cDNA sequence and mRNA tissue distribution of a novel human matrix
      metalloproteinase with a potential transmembrane segment.
AB  - The complementary DNA sequence of a novel matrix metalloproteinase was isolated
      from a human lung cDNA library. It consists of 3530 bp and encodes a polypeptide
      of 669 amino acids. In comparison to other matrix metalloproteinases, the deduced
      sequence of the amino acid chain exhibits closest similarity to a recently
      discovered membrane-type matrix metalloproteinase of 582 amino acids. Likewise,
      it is composed of a signal peptide, a prodomain, a catalytic domain, a hemopexin
      homologous domain and a C-terminal domain. Furthermore, the novel matrix
      metalloproteinase shares a similar activation site with its 582-amino-acid
      homologue, an insertion of eight amino acids in the catalytic domain and a tract
      of more than 20 hydrophobic amino acids near the C-terminus. The hydrophobic
      structure in the C-terminal domain suggests that the novel matrix
      metalloproteinase is also membrane bound. When lung cell membrane fractions were
      probed in immunoblots with polyclonal antibodies against a recombinant fragment
      of the 669-amino-acid chain, a protein of M(r) 72,000 reacted preferentially with
      the antibodies. Northern-blot analysis demonstrated quite different tissue
      distributions of mRNA for the two membrane-type matrix metalloproteinases. While
      mRNA for the 582-amino-acid enzyme was found predominantly in lung, placenta,
      kidney, ovary, intestine, prostate and spleen, mRNA for the 669-amino-acid enzyme
      appeared to be synthesized preferentially in liver, placenta, testis, colon and
      intestine. Substantial amounts of the latter mRNA were also detected in pancreas,
      kidney, lung, heart and skeletal muscle.

PMID- 7649160
TI  - Structure and differential expression of two maize ferritin genes in response to
      iron and abscisic acid.
AB  - In plants, synthesis of the iron-storage protein ferritin in response to iron is
      not regulated at the translational level; this is in contrast to ferritin
      synthesis in animals. Part of the response is mediated through a transduction
      pathway which involves the plant hormone abscisic acid. In this work, we report
      the cloning and sequencing of two maize ferritin genes (ZmFer1 and ZmFer2) coding
      for members of the two ferritin mRNA subclasses, FM1 and FM2, respectively.
      Although plant and animal ferritins are closely related proteins, a major
      difference is observed between the organisation of the genes. Both maize ferritin
      genes are organised as eight exons and seven introns, the positions of which are
      identical within the two genes, while animal ferritin genes are interrupted by
      three introns, at positions different from those found in maize genes. Sequence
      divergence between the 3' untranslated regions of these genes has allowed the use
      of specific probes to study the accumulation of FM1 and FM2 transcripts in
      response to various environmental cues. Such probes have shown that FM1 and FM2
      transcripts accumulate with differential kinetics in response to iron; FM1 mRNA
      accumulate earlier than FM2 mRNA and only FM2 transcripts accumulate in response
      to exogenous abscisic acid or water stress. Mapping of the transcriptional
      initiation region of these two genes defined their 5' upstream regions and
      allowed a sequence comparison of their promoters, which appeared highly
      divergent. This raises the possibility that the differential accumulation of FM1
      and FM2 mRNAs in response to iron, abscisic acid and drought could be due to
      differential transcription of ZmFer1 and ZmFer2.

PMID- 7649161
TI  - Transcriptional repression, a novel function for 3' untranslated regions.
AB  - The transcription rates of the rat serine protease inhibitor 2.3 and 2.1 genes
      (spi 2.3 and spi 2.1), which are normally very low and high, respectively, are
      inversely modulated during inflammation. Two growth-hormone-response elements
      (GHRE-I and GHRE-II) maintain the spi 2.1 gene under the stringent control of
      growth hormone [Le Cam, A., Pantescu, V., Paquereau, L., Legraverend, C.,
      Fauconnier, G. & Asins, G. (1994) J. Biol. Chem. 269, 21532-21539], whereas spi
      2.3 appears to escape control by this hormone, despite the presence in its
      promoter of a functional GHRE-I. A major difference between these two otherwise
      very similar genes is the presence in spi 2.3 of a specific 348-bp extension of
      the 3' untranslated region (3' UTR). Inserting this 3' UTR element downstream of
      the polyadenylation signal or upstream of the spi 2.3 promoter in constructs
      containing the chloramphenicol acetyltransferase gene strongly decreases basal
      transcription and inhibits growth-hormone-stimulated transcription, but poorly
      affects transcriptional stimulation by dexamethasone or interleukin-6. The spi
      2.3 3' UTR extension also inhibits, basal and growth-hormone-induced
      transcription from the spi 2.1 promoter. Repressor activity appears to be
      distributed throughout the specific extension of the 3' UTR and seems to involve
      interactions with two types of 5' cis-acting promoter elements. The first is the
      GAGA box, a key control spi promoter element, whose mutation faithfully
      reproduces the effects of the 3' UTR silencer on spi 2.1 and spi 2.3 promoters.
      The second is represented by CCAAT enhancer-binding-protein-(C/EBP)-binding
      sites, whose functions are severely impaired by the spi 2.3-specific 3' UTR
      extension. The presence of this silencer in the spi 2.3 gene very likely accounts
      for the lack of basal of transcription in vivo and for induction of the gene
      during acute inflammation.

PMID- 7649162
TI  - Characterization of a 45-kDa flavoprotein and evidence for a rubredoxin, two
      proteins that could participate in electron transport from H2 to CO2 in
      methanogenesis in Methanobacterium thermoautotrophicum.
AB  - Methanobacterium thermoautotrophicum strains contain a flavoprotein (flavoprotein
      A) that copurifies with the H2:heterodisulfide oxidoreductase complex. In this
      study, we report the iron-dependent synthesis and biochemical properties of
      flavoprotein A, cloning and sequencing of the flavoprotein-A-encoding gene (fpaA)
      and the co-transcription of fpaA with two downstream open reading frames, one of
      which (rdxA) appears to encode a rubredoxin. Native flavoprotein A has been shown
      to be a homodimer of a 45-kDa polypeptide that contains 1.3 mol FMN/45-kDa
      subunit but no iron or acid-labile sulfur. Catalytic amounts of the
      H2:heterodisulfide oxidoreductase complex or of the F420-reducing hydrogenase
      reduced flavoprotein A with H2, at specific rates of 0.3-0.4 U/mg enzyme,
      generating up to 70% flavin semiquinone before reduction to the flavin
      hydroquinone was observed. This intermediate accumulation of the semiquinone
      species had a kinetic rather than a thermodynamic basis, because the semiquinone
      form of flavoprotein A, generated by photoreduction, disproportionated
      quantitatively to the quinone and hydroquinone species. The midpoint potential of
      the quinone/hydroquinone couple was estimated to be 230 +/- 15 mV, at pH 7.6,
      versus the normal hydrogen electrode. Quantitation of Western blots demonstrated
      that flavoprotein A constituted approximately 1.5% of the soluble protein in
      cells grown in an iron-sufficient medium but that this increased to about 6% of
      the cellular protein when the iron the medium was depleted. The increase in the
      flavoprotein A content of cells grown under iron-limiting conditions was mirrored
      by a decrease in the content of the iron-rich polyferredoxin that also copurified
      with the H2:heterodisulfide oxidoreductase complex. The fpaA gene, cloned and
      sequenced from M. thermoautotrophicum strain delta H, encodes 404 amino acids in
      a sequence that has a C-terminal domain (approximately 130 amino acid residues)
      with features consistent with a flavodoxin structure. The remainder of
      flavoprotein A has sequences that are also predicted to be present in the N
      terminal region of the orf14 gene product, which also appears to be an enlarged
      flavodoxin, encoded in the nif region of Rhodobacter capsulatus. Immediately
      downstream from fpaA, two open reading frames designated orfX and rdxA, have been
      located and shown by Northern-blot analyses to be co-transcribed with fpaA,
      although approximately 50% of fpaA-orfX-rdxA transcripts terminated or were
      cleaved within rdxA. Primer extension studies revealed that transcription of this
      transcriptional unit (the fpa operon) was initiated 32 nucleotides upstream of
      fpaA, at a site 25 nucleotides downstream from a sequence consistent with an
      archaeal TATA-box promoter element.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7649163
TI  - Overproduction in Escherichia coli, purification and properties of human
      prothymosin alpha.
AB  - A bacterial strain overproducing human prothymosin alpha was constructed based on
      the efficient T7 RNA polymerase transcription of human prothymosin alpha cDNA.
      The highest yield of the human prothymosin alpha, up to 30% of the total
      bacterial protein, was achieved with constructions containing 6-10 nucleotides
      between the Shine-Dalgarno sequence and initiation ATG codon. Unexpectedly, cells
      grown in the presence of inducer of T7 RNA polymerase synthesis produced
      substantially lower levels of prothymosin alpha than those grown in the absence
      of inducer. A simple procedure for prothymosin alpha isolation was elaborated,
      resulting in large amounts of electrophoretically pure and immunoactive protein.

PMID- 7649164
TI  - Characterization of the binary interaction between human erythrocyte protein 4.1
      and actin.
AB  - The binary interaction between human erythrocyte protein 4.1 and rabbit skeletal
      muscle F-actin was examined by rapid pelleting of the binary complexes. The
      binding curves show that the reaction was saturable at approximately one protein
      4.1 molecule/actin monomer. The reaction was highly co-operative, displaying a
      Hill coefficient close to 2. Using a fixed concentration of radiolabelled protein
      4.1, and varying the concentration of F-actin, the apparent molar association
      constant, Ka, was observed to range from 5 x 10(4) M-1 to > 10(6) M-1. The binary
      interaction between erythrocyte spectrin and actin was also observed to be co
      operative under the same conditions. The rate of reaction between protein 4.1 and
      actin was temperature sensitive in a manner consistent with a high energy of
      activation. The pelleting assay also showed that the concentration of actin was
      reduced in the supernatant in the presence of protein 4.1 compared with actin
      alone, indicating that the critical concentration of actin was lowered in the
      presence of protein 4.1. Polyvalent anions disrupted the binary interaction
      between F-actin and protein 4.1, the disruption being consistent with the number
      of negative charges on these anions at pH 7.5. We postulate that the co
      operativity of the binding of protein 4.1 to actin results from a protein 4.1
      molecule binding to a single monomer within the filament structure which then
      promotes conformational changes allowing further protein 4.1 binding. The
      demonstration of a specific binary association between protein 4.1 and actin
      suggests that this interaction contributes significantly to the stabilization of
      the spectrin-actin-protein-4.1 ternary complex.

PMID- 7649165
TI  - Characterization of monoclonal antibodies that strongly inhibit Electrophorus
      electricus acetylcholinesterase.
AB  - In this study, we describe three different monoclonal antibodies (mAbs Elec-403,
      Elec-408, and Elec-410) directed against Electrophorus electricus
      acetylcholinesterase (AChE) which were selected as inhibitors for this enzyme.
      Two of these antibodies (Elec-403 and Elec-410), recognized overlapping but
      different epitopes, competed with snake venom toxin fasciculin for binding to the
      enzyme, and thus apparently recognized the peripheral site of AChE. In addition,
      the binding of Elec-403 was antagonized by 1,5-bis(4
      allyldimethylammoniumphenyl)pentan-3-one dibromide (BW284C51) and propidium,
      indicating that the corresponding epitope encompassed the anionic site involved
      in the binding of these low-molecular-mass inhibitors. The third mAb (Elec-408),
      was clearly bound to another site on the AChE molecule, and its inhibitory effect
      was cumulative with those of Elec-403, Elec-410, and fasciculin. All mAbs bound
      AChE with high affinity and were as strong inhibitors with an apparent Ki values
      less than 0.1 nM. Elec-403 was particularly efficient with an inhibitory activity
      similar to that of fasciculin. Inhibition was observed with both charged
      (acetylthiocholine) and neutral substrates (o-nitrophenyl acetate) and had the
      characteristics of a non-competitive process. Elec-403 and Elec-410 probably
      exert their effect by triggering allosteric transitions from the peripheral site
      to the active site. The epitope recognized by mAb Elec-408 has not been
      localized, but it may correspond to a new regulatory site on AChE.

PMID- 7649166
TI  - In vitro inactivation of yeast glutathione reductase by tetramethylthiuram
      disulphide.
AB  - Previous in vivo investigations have shown that glutathione reductase is one of
      the sites of action of the dithiocarbamate fungicide tetramethylthiuram
      disulphide (thiram) in the yeast Saccharomyces cerevisiae. The inactivation of
      glutathione reductase by thiram has now been demonstrated in vitro. This
      inactivation was time-dependent and occurred only with the enzyme in the reduced
      state and in the absence of glutathione. Since the turnover rate of the enzyme
      with thiram as a substrate was significantly higher than the rate of enzyme
      inactivation, it was suggested that more than one enzyme-inhibitor complex was
      involved in the reaction. Arguments supporting a covalent modification of
      glutathione reductase were further obtained by experiments carried out with
      [14C]thiram and gel filtration. A kinetic scheme for the inactivation is proposed
      and the relevance of the in vitro data to previous in vivo studies is discussed
      taking into consideration current concepts of glutathione reductase inactivation
      by affinity reagents.

PMID- 7649168
TI  - K(+)-H+ exchange activity in brush-border membrane vesicles isolated from chick
      small intestine.
AB  - The purpose of this study was to investigate the presence of a K(+)-H+ exchanger
      in brush-border membrane vesicles (BBMV) isolated from chick small intestine.
      86Rb+, as a tracer for K+ transport, was used to probe for the exchange
      mechanism. An outwardly directed proton gradient (pH 5.5 inside, pH 7.5 outside)
      stimulated 86Rb+ uptake into voltage-clamped BBMV. H(+)-driven 86Rb+ uptake was
      only weakly inhibited by 5-(N-ethyl-N-isopropyl)amiloride, whereas this agent
      strongly inhibited H(+)-driven Na+ uptake. At initial rates, proton-driven 86Rb+
      uptake was significantly reduced by external K+ but it was not significantly
      affected by external Na+. Conversely, extravesicular Na+ inhibited proton-driven
      Na+ uptake, whilst K+ had little effect. H(+)-driven K+ uptake tended to saturate
      with increasing external K+ concentrations and Lineweaver-Burk analysis of the
      data revealed a Km for external K+ of 2 mM. These findings are consistent with
      the presence of K(+)-H+ exchange activity in the chicken jejunal brush-border
      membrane.

PMID- 7649167
TI  - Comparison of the specificity of bacterially expressed cytoplasmic protein
      tyrosine phosphatases SHP and SH-PTP2 towards synthetic phosphopeptide
      substrates.
AB  - SHP and SH-PTP2 are related cytoplasmic protein-tyrosine phosphatases having two
      tandem amino-terminal src homology 2 domains linked to a single catalytic domain.
      There is growing evidence that these two molecules may exhibit opposing effects
      within specific signaling pathways. However, the relative contributions of the
      src homology 2 domains or the catalytic domains to these opposing effects are not
      well known. To evaluate the potential contribution of the catalytic domains, we
      compared the substrate specificity of the two phosphatases. As seen previously,
      the catalytic activities of bacterially expressed SHP and SH-PTP2 were regulated
      by the presence of the linked src homology 2 domains. In addition, we
      characterized a cryptic thrombin cleavage site within the carboxy-terminus of SHP
      that led to a striking increase in the activity of the catalytic domain.
      Employing a panel of phosphopeptide substrates whose sequences were modeled after
      intracellular phosphorylation sites, both SHP and SH-PTP2 demonstrated a similar
      specificity pattern. Similar to SH-PTP2, SHP failed to elicit detectable
      phosphate release from several phosphopeptide substrates, while displaying
      catalytic efficiencies that ranged over approximately 40-1.6 x 10(3) M-1 s-1
      towards other substrates. In contrast, the PTP-1B phosphatase dephosphorylated
      all of the phosphopeptide substrates tested with approximately equal ease. The
      overall similarity demonstrated by the catalytic domains of SHP and SH-PTP2
      suggested that differences in the in vivo behavior of these two molecules might
      not stem from differences in the substrate specificity of the catalytic domains,
      suggesting instead that the specificity of the src homology 2 domains is more
      important in this regard.

PMID- 7649169
TI  - Fatty acids regulate Thy-1 antigen mRNA stability in T lymphocyte precursors.
AB  - In this study, we report the effect of fatty acids on the Thy-1 antigen mRNA
      decay. Low serum and synthetic medium culture conditions were used to demonstrate
      that fatty acids, which are important metabolites involved as second messengers
      in signal transduction, also influence the steady-state mRNA level. Detailed
      analysis demonstrated that polyunsaturated lipids attached to bovine serum
      albumin, such as linoleic, linolenic, and arachidonic acids, modulate gene
      expression specifically in the S1A T lymphoma cell line by inducing a 3-5-fold
      increase in the steady-state Thy-1 mRNA level, concomitant with a twofold
      increase in cell surface expression. A similar modulation was observed in the
      immature CD4-CD8- T cell precursors but not in mature thymocytes. Nuclear run-on
      and transfection experiments indicated that the observed Thy-1 mRNA level is post
      transcriptionally regulated and that the presence of the coding region is
      sufficient for this adaptive response. A mechanism without a requirement for
      protein kinase C activation, but involving Ca2+ entry, could account for this
      difference in Thy-1 mRNA stability.

PMID- 7649170
TI  - Comparative analysis of 13C-enriched metabolites released in the medium of
      cerebellar and cortical astrocytes incubated with [1-13C]glucose.
AB  - Rat cerebellar and cortical astrocytes cultured for 15 or 35 days were incubated
      with [1-13C]glucose in the presence or absence of 4 mM exogenous glutamine and
      the release of 13C-enriched metabolites into cell media was studied by 13C-NMR
      spectroscopy. In the presence of exogenous glutamine, both cerebellar and
      cortical astrocytes consumed the amino acid. In contrast, a net production of
      glutamine occurred in the absence of the amino acid. Simultaneously, a release of
      13C-enriched glutamine into cell media was observed and was higher in the
      presence than in the absence of exogenous glutamine. This demonstrated the
      occurrence of an isotopic-exchange process which may involve a futile cycle at
      the level of glutamine synthetase and glutaminase activities. The 13C-enrichment
      ratio between glutamine carbons C2 and C3 was close to 1 in the presence of
      exogenous glutamine whereas it was higher than 1 in its absence, indicating that
      pyruvate carboxylase was more active in the absence of glutamine. In addition to
      glutamine, alanine was synthesized and exported into the medium of both
      cerebellar and cortical astrocytes. In contrast, citrate was specifically
      produced by cortical astrocytes. Slight increases in alanine and glutamine
      productions were observed for cortical astrocyte cultures between 15 and 35 days,
      whereas the amino acid production by cerebellar astrocytes increased several-fold
      after 35 days compared with that at 15 days of culture.

PMID- 7649171
TI  - ACS2, a Saccharomyces cerevisiae gene encoding acetyl-coenzyme A synthetase,
      essential for growth on glucose.
AB  - In Saccharomyces cerevisiae, the conversion of pyruvate to acetyl-coenzyme A may
      proceed directly via the pyruvate dehydrogenase complex (PDH) or indirectly via
      the so-called PDH bypass, which requires the sequential action of pyruvate
      decarboxylase, acetaldehyde dehydrogenase and acetyl-coenzyme A synthetase. The
      relative contribution of both pathways to the rate of acetyl-coenzyme A synthesis
      varies in an unknown way with cultural conditions. To determine the possible role
      of acetyl-coenzyme A synthetase in this central part of metabolism, we have
      analyzed the genes encoding this enzyme. Disruption of the recently cloned ACS1
      gene [De Virgilio, C., Burckert, N., Barth, G., Neuhaus, J., Boller, T. &
      Wiemken, A. (1992) Yeast 8, 1043-1051] did not cause an apparent phenotype,
      except for a prolonged lag-phase during growth on glucose or C2 compounds such as
      acetate and ethanol. In fact, a product from a different gene is responsible for
      acetyl-coenzyme A formation in the acs1 mutant. We cloned a second gene encoding
      acetyl-coenzyme A synthetase, which we called ACS2. Inactivation of this gene
      caused inability to grow on media containing glucose, but not on media with
      acetate or ethanol as the sole carbon source. This indicates that ACS2 is
      essential for growth on glucose in batch cultures. The acs1-acs2 double mutant
      was not viable. The role of both genes in glucose metabolism and acetate or
      ethanol metabolism is discussed.

PMID- 7649172
TI  - Evidence for the tissue inhibitor of metalloproteinases-1 (TIMP-1) in human
      polymorphonuclear leukocytes.
AB  - A tissue inhibitor of metalloproteinases (TIMP)-1 was isolated from human
      polymorphonuclear leukocytes (PMNL) in a complex with latent 95-kDa gelatinase
      (matrixmetalloproteinase, MMP-9). It was separated from the enzyme by gel
      filtration in the presence of SDS. Using a competitive ELISA procedure, we
      determined that 10% of the isolated gelatinase was complexed with TIMP-1. The
      presence of the inhibitor in isolated PMNL could also be demonstrated by indirect
      immunofluorescence using a specific antibody against TIMP-1. Cellular mRNA was
      isolated from PMNL, which were highly purified by separation via formylMet-Leu
      Pro-stimulated chemotactic migration in a Boyden chamber. Using reverse
      transcription PCR and Northern blotting, TIMP-1 mRNA was shown to be present in
      PMNL, suggesting that these cells are also capable of synthesizing TIMP-1.

PMID- 7649173
TI  - Cloning and sequencing a non-ATPase subunit of the regulatory complex of the
      Drosophila 26S protease.
AB  - We have cloned and sequenced a non-ATPase subunit of the regulatory complex of
      the Drosophila 26S protease. The gene is present in a single copy in the
      Drosophila genome. By comparing the nucleotide sequence of the genomic and cDNA
      clones three exons and two introns were localized. Two transcription start sites
      were identified 9 bp apart. The deduced protein sequence shows no significant
      similarity to any other protein in the database. In Drosophila embryos where the
      26S protease is present in high concentration, the pool of free subunits of the
      regulatory complex is very low. Among the free subunits of the regulatory complex
      the cloned subunit is present in very large excess. This observation raises the
      possibility that this subunit is in a dynamic equilibrium, exchanging between a
      free and a particle-bound form, which may have important implications concerning
      its function.

PMID- 7649174
TI  - Binding of a fluorescent nucleotide analog to Hsc70. The effect of peptide
      protein interactions on the luminescence properties of the probe.
AB  - 2'-Deoxy-3'-anthraniloyladenosine-5-triphosphate(Ant-dATP) was used as an
      environmentally sensitive probe of the nucleotide-binding site of the molecular
      chaperone Hsc70. When coordinated to the lanthanide ion Tb3+, Ant-dATP is not
      hydrolyzed by Hsc70. The lanthanide ion acts as strong competitive inhibitor with
      respect to Mg2+ (Ki = 0.1 microM). Tb.Ant-dATP recognizes the nucleotide site of
      Hsc70 as revealed by an increase in the emission anisotropy from 0.03 to 0.21 and
      by a change in the fluorescence-decay time from 2.52 ns to 3.75 ns. Sensitized
      luminescence arising from resonance energy transfer from the anthraniloyl group
      to Tb3+ is substantially enhanced in the presence of Hsc70. Binding of a 20-amino
      acid-residue peptide (Rnase-S peptide) to Hsc70 causes a blue shift in the
      fluorescence spectrum of Ant-dATP and enhances Tb3+ luminescence upon excitation
      at 330 nm. It is postulated that binding of the peptide to the COOH-terminal
      domain of Hsc70 initiates domain movement and the structural changes might extend
      to the nucleotide-binding site.

PMID- 7649175
TI  - A Rhizobium meliloti ferredoxin (FdxN) purified from Escherichia coli donates
      electrons to Rhodobacter capsulatus nitrogenase.
AB  - The fdxN gene from Rhizobium meliloti encoding a bacterial-type ferredoxin (FdxN)
      was expressed in Escherichia coli under the control of the lac promoter. The fdxN
      gene product was purified under anaerobic conditions by ion-exchange
      chromatography and gel-filtration steps using an antiserum raised against an FdxN
      LacZ fusion protein as a detection system. The purified ferredoxin was shown to
      be identical to the predicted R. meliloti FdxN protein in its amino acid
      composition and N-terminal amino acid sequence. Chemical determination of the
      iron content revealed 8.6 +/- 0.6 mol Fe/mol FdxN. The ultraviolet/visible
      absorption spectrum of the FdxN protein in the oxidized form exhibited maxima at
      284 nm and 378 nm, with an A378/A284 ratio of 0.7. EPR spectroscopy revealed a
      rhombic signal when FdxN was partially reduced, and a broad signal indicative of
      spin-spin interaction when fully reduced, suggesting the presence of two Fe-S
      cluster/ferredoxin polypeptide. Our data suggest that FdxN contains two [4Fe-4S]
      clusters. Purified FdxN was able to mediate electron transport between
      illuminated chloroplasts and Rhodobacter capsulatus nitrogenase in vitro.

PMID- 7649176
TI  - An extended binding pocket determines the polar head group specificity of porcine
      pancreatic phospholipase A2.
AB  - Porcine pancreatic phospholipase A2 (PLA2) was studied by site-directed
      mutagenesis. Arg53 and/or Lys56 were replaced by a methionine (R53M or K56M,
      respectively) in combination with the Tyr69-->Phe (Y69F) substitution. These
      substitutions improved the activity on micellar and monomeric zwitterionic
      substrates and reduced the activity on negatively charged substrates compared to
      the Y69F mutant. With the neutral substrate 1,2-didodecanoyl-sn-glycerol-3
      dimethyl phosphate (Lau2GroMe2P) a 20-fold increase of activity was observed for
      the 69F53M56M mutant, whereas this mutant showed a lower activity than native
      PLA2 on zwitterionic substrates. Thus the ratio Lau2GroMe2P/Lau2GroPCho has
      become 65 times higher for 69F53M56M compared to native phospholipase A2,
      illustrating that the substrate specificity has changed enormously. The
      methionine substitutions were also prepared in a 69F mutant in which a part of
      the surface loop (residues 62-66) was deleted. Also in this deletion mutant these
      substitutions showed a similar effect as the substitutions in the native 69F
      mutant. Furthermore it was shown that deletion of the loop increases the activity
      on micellar lecithins and negatively charged micellar substrates, but reduces the
      activity on Lau2GroMe2P. Therefore it can be concluded that the loop is important
      for the recognition of substrates. We also show that the loop plays a role in the
      dimerization of these proteins. Dimerization may account for the high activities
      observed for some mutants acting on monomeric substrate.

PMID- 7649177
TI  - Coenzyme F420-dependent N5,N10-methylenetetrahydromethanopterin reductase (Mer)
      from Methanobacterium thermoautotrophicum strain Marburg. Cloning, sequencing,
      transcriptional analysis, and functional expression in Escherichia coli of the
      mer gene.
AB  - The gene encoding the F420-dependent N5,N10-methylenetetrahydromethanopterin
      reductase (Mer), which catalyzes an intermediate step in methanogensis, was
      cloned and sequenced from the thermophilic Methanobacterium thermoautotrophicum
      strain Marburg. The gene was identified on a 3.8-kbp BamHI fragment of M.
      thermoautotrophicum genomic DNA using a homologous probe. The mer gene encoded an
      acidic protein of 321 amino acids, corresponding to a calculated molecular mass
      of 33,492 Da. Sequence analysis revealed the presence of a ribosome binding site,
      a putative promoter, and a possible terminator structure. The size of the mer
      mRNA was estimated as 1 kb indicating monocistronic transcription. The mer gene
      was expressed in Escherichia coli yielding an active enzyme of 36 kDa consistent
      with the apparent molecular mass described for the enzyme from M.
      thermoautotrophicum. Sequence comparisons revealed similarities between the F420
      dependent N5,N10-methylenetetrahydromethanopterin reductase and a F420-dependent
      reductase involved in lincomycin biosynthesis in Streptomyces lincolnensis.

PMID- 7649178
TI  - 13C-NMR spectroscopy of keratan sulphates. Assignments for four poly(N
      acetyllactosamine)-repeat-sequence tetrasaccharides derived from bovine articular
      cartilage keratan sulphate by keratanase II digestion.
AB  - Skeletal keratan sulphate has been fragmented using the enzyme keratanase II, and
      the complete 13C chemical shift data are reported for the four tetrasaccharides
      which derived from the repeat region. They have the structures: Gal beta(1
      4)GlcNAc(6S)beta(1-3)Gal beta(1-4)GlcNAc(6S)-ol, Gal(6S)beta(1-4)GlcNAc(6S)beta(1
      3)Gal(1-4)GlcNAc(6S)-ol, Gal beta(1-4)GlcNAc(6S)beta(1-3)Gal(6S)beta(1
      4)GlcNAc(6S)-ol, and Gal(6S)beta(1-4)GlcNAc(6S)(1-3)Gal(6S)beta(1-4)GlcNAc(6S)
      ol, where GlcNAc(6S)-ol represents N-acetyl-glucosaminitol-6-O-sulphate. The
      value of these data for microstructural analysis of undegraded keratan sulphate
      samples using 13C-NMR spectroscopy is discussed with respect to galactose
      sulphation levels and the block sulphation structure.

PMID- 7649179
TI  - Synthesis of the oxaloacetate decarboxylase Na+ pump and its individual subunits
      in Escherichia coli and analysis of their function.
AB  - The oadGAB genes encoding the gamma, alpha and beta-subunits of the oxaloacetate
      decarboxylase Na+ pump in Klebsiella pneumoniae have been cloned on plasmid pSK
      GAB and expressed in Escherichia coli. The membranes of the recombinant E. coli
      clone contained about three times as much catalytically active oxaloacetate
      decarboxylase (3 mg protein/2 g wet cells) as those of the K. pneumoniae strain
      from which the genes were derived. The enzyme was solubilised from the membranes
      with Triton X-100 and purified. Its Na+ transport function was demonstrated after
      reconstitution into proteoliposomes. Proteoliposomes containing only the membrane
      bound subunits beta and gamma (not the peripheral alpha-subunit) were unable to
      catalyse Na+ translocation in response to a transmembrane Na+ (delta pNa+) or
      electrical gradient (delta psi). Individual subunits of oxaloacetate
      decarboxylase and combinations of two subunits were expressed from appropriate
      derivatives of plasmid pSK-GAB. The hydrophobic subunits beta and beta gamma were
      membrane-bound as expected. Interestingly, the alpha-subunit was located in the
      cytoplasm if expressed separately or together with beta, but became membrane
      bound if expressed together with gamma. A gamma alpha complex was isolated from
      such membranes by avidin-Sepharose affinity chromatography. Interactions of the
      gamma-subunit with the water-soluble alpha-subunit and with the membrane-bound
      beta-subunit are therefore required to form the oxaloacetate decarboxylase
      complex. The combinations of separately expressed subunits gamma alpha + beta and
      beta gamma+alpha were shown to yield the catalytically active enzyme. The alpha
      or the beta-subunit and the combinations of these subunits with the gamma-subunit
      were therefore expressed in E. coli in a catalytically competent state.
      Functional expression of the separate gamma-subunit, however, could not be
      demonstrated. The alpha-subunit was strongly overexpressed from a pT7-7 derived
      plasmid, but was only partially biotinylated under these conditions. On
      coexpression of the birA gene encoding biotin ligase the major part (80-100%) of
      the overexpressed alpha-subunit was biotinylated. Highly purified alpha-subunit
      was obtained by fractionated precipitation of the soluble cell fraction with
      ammonium sulfate. Incubation of the alpha-subunit with oxaloacetate led to a CO2
      transfer to its prosthetic biotin group with the formation of stoichiometric
      amounts of pyruvate. The velocity of the CO2 transfer to the biotin on the alpha
      subunit was about three orders of magnitude too low to account for the rate of
      the overall reaction. The carboxyltransfer reaction was significantly accelerated
      if the gamma-subunit was additionally present.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7649180
TI  - Functional identification of three major phosphoproteins in endocytic fractions
      from rat liver. A comparative in vivo and in vitro study.
AB  - Liver plasma membranes originating from the sinusoidal, lateral and canalicular
      domains and 'early' and 'late' endosomes were prepared from rats injected with
      [32P]orthophosphate. The phosphorylated polypeptides in these subcellular
      fractions, resolved by gel electrophoresis, were analysed and compared with those
      obtained by in vitro phosphorylation of the fractions by endogenous protein
      kinases. The polypeptides phosphorylated in vitro were different in plasma
      membranes, endosomes and lysosomes. Three of the major phosphoproteins in the
      endocytic membranes were shown to be the polymeric immunoglobulin receptor, the
      beta subunit of the insulin receptor and the 550-kDa low-density-lipoprotein
      receptor-related protein (LRP). An additional 35-kDa polypeptide of unknown
      function was a major phosphorylated component and thus emerges as a candidate
      marker protein of hepatic endosomes. Phosphoserine was shown to be the major
      amino acid phosphorylated in vitro in the phosphoproteins of endocytic membranes.
      The subcellular distribution in liver tissue of protein kinase activity was also
      investigated and activity shown to be recovered mainly in blood-sinusoidal and
      lateral plasma membranes; bile canalicular plasma membranes and endosomes
      contained low protein kinase activities. The results show that receptor
      phosphorylation is an 'early' event in endocytosis and the trafficking of ligands
      that is sustained especially in early endosomes in liver, and emphasizes the
      biochemical and thus functional distinctiveness of the plasma membrane and the
      endosomal and lysosomal compartments with regard to their population of
      phosphorylated proteins.

PMID- 7649181
TI  - Molecular characterization of the mouse prostanoid EP1 receptor gene.
AB  - A partial cDNA, corresponding to the mouse prostaglandin E2 receptor subtype EP1,
      was isolated from mouse brain cDNA using a degenerate primer PCR strategy. Using
      the cDNA fragment as a probe, the EP1 receptor gene was isolated and
      characterized. The gene consists of three exons, of which the first is non
      coding, and is contained within a 3.5-kb region. The coding nucleotide sequence
      determined is identical to that of the published mouse EP1 cDNA. The positions of
      the introns correspond to those of the thromboxane A2 and prostaglandin D
      receptor genes. No alternative splicing of the EP1 receptor gene could be
      detected. PCR and specific primers designed from the genomic sequence were used
      to amplify the coding part of the isolated gene from kidney cDNA. The cDNA
      obtained was cloned into a eukaryotic expression vector, and stably transfected
      Chinese hamster ovary cell lines were established. The cells respond to
      prostaglandin E2 with intracellular Ca2+ mobilization, as expected for this
      prostanoid receptor subtype. In situ hybridization was used to localize the EP1
      receptor transcript in different mouse tissues. Significant hybridization was
      detected only in the collecting ducts of the kidney, and in the paraventricular
      and supraoptic nuclei of the hypothalamus. The expression of the EP1 receptor in
      the hypothalamus suggests that this prostanoid receptor is involved in mediating
      the fever response evoked by prostaglandin E2.

PMID- 7649182
TI  - Purification and characterization of an alpha-methylacyl-CoA racemase from human
      liver.
AB  - A specific racemase for alpha-methylacyl-CoAs, which had previously been studied
      in rat liver [W. Schmitz, R. Fingerhut, E. Conzelmann (1994) Eur. J. Biochem.
      222, 313-323], has now been demonstrated also in human tissues. The human enzyme
      cross-reacts with a polyclonal antiserum against the rat liver racemase. The
      racemase was purified from human liver some 3600-fold. It is a monomer of 47 kDa
      with an isolectric point of pH 6.1 and is optimally active between pH 7-8. It
      acts only on coenzyme A thioesters, not on free fatty acids, and accepts as
      substrates a wide range of alpha-methylacyl-CoAs, including pristanoyl-CoA and
      trihydroxycoprostanoyl-CoA (an intermediate in bile acid synthesis), but neither
      3-methyl-branched nor linear-chain acyl-CoAs. A clear difference in subcellular
      localization of the enzyme was found between humans and rats: the rat enzyme co
      distributed exclusively with mitochondrial marker enzymes whereas in human cells,
      only 10-30% of the activity was found in mitochondria, the bulk activity was
      located in peroxisomes. Cells from patients with general deficiency of peroxisome
      assembly (Zellweger syndrome) showed strongly reduced racemase activity, with
      only the mitochondrial share being present while the peroxisomal form was absent.

PMID- 7649183
TI  - Isolation and structural characterization of trimeric cyanobacterial photosystem
      I complex with the help of recombinant antibody fragments.
AB  - A monoclonal antibody was derived from mice immunized with the native trimeric,
      photosystem I (PSI) complex from the cyanobacterium Synechococcus PCC 7002 which
      reacts with a conformational epitope of the PSI complex. As seen by
      immunoelectron microscopy, the mAb bound to the stromal side of the thylakoid
      membranes. The DNA sequence encoding variable regions of the mAb was cloned into
      recombinant plasmids, sequenced and expressed in Escherichia coli. ELISA, Western
      blots and immunoelectron microscopy provided evidence that the expressed paired
      variable domain (Fv) fragments bind to the antigen in the same way as the parent
      mAb. A one-step purification was applied to purify the trimeric PSI complex using
      an affinity tag attached to the Fv fragment. Analysis by gel electrophoresis and
      N-terminal sequencing revealed the presence of the psaA, psaB, psaC, psaD, psaE,
      psaF and psaL gene products. The antenna size of the isolated PSI/Fv was 139 +/-
      9 chlorophyll a/primary electron donor. Flash-induced absorption-change
      measurements showed that the complex exhibited electron transfer from the primary
      electron donor, P700, to the Fe-S center, FA/FB. The position of the bound Fv
      fragment on the trimeric PSI surface was determined by high-resolution electron
      microscopy and digital image processing.

PMID- 7649184
TI  - Purification and molecular cloning of a major antibacterial protein of the
      protozoan parasite Entamoeba histolytica with lysozyme-like properties.
AB  - A protein with potent antibacterial activity was purified to apparent homogeneity
      from pathogenic Entamoeba histolytica. It resembles lysozyme in that it is a
      basic protein which degrades cell walls of Micrococcus luteus, displays optimal
      activity at acidic pH, and shows a preference for Gram-positive bacteria. The
      protein has a molecular mass of approximately 23 kDa upon SDS/PAGE and is
      localized inside the cytoplasmic granules of the amoebae. The primary structure
      was elucidated by protein analysis and molecular cloning of the corresponding
      cDNA. It yielded a protein of 198 residues with structural similarity to the
      distinct class of lysozymes found in Streptomyces species and the fungus
      Chalaropsis.

PMID- 7649185
TI  - Characterization and gene cloning of 1,3-beta-D-glucan synthase from
      Saccharomyces cerevisiae.
AB  - 1,3-beta-D-Glucan synthase of Saccharomyces cerevisiae was solubilized and
      purified up to 700-fold by product entrapment. The specific activity of the
      partially purified enzyme was around 4 mumol glucose incorporated.min-1.mg
      protein-1. In SDS/PAGE, enrichment of a 200-kDa protein was clearly observed in
      parallel with the increase in specific activity. mAbs that could
      immunoprecipitate the 1,3-beta-D-glucan synthase activity were isolated, and some
      of them also recognized this 200-kDa protein in the Western blot. Internal amino
      acid sequences of this 200-kDa protein were determined after lysyl endopeptidase
      digestion. With the information of these amino acid sequences, we cloned two
      genes, GSC1 and GSC2 (glucan synthase of S. cerevisiae 1 and 2), which are very
      similar to each other (88% at the amino acid level); hydropathy profiles of both
      proteins suggest that these genes encode integral membrane proteins which can be
      assumed to have approximately 16 transmembrane domains. Disruption of each gene
      was not lethal, but disruption of both genes was lethal. The 1,3-beta-D-glucan
      synthase activities of membrane and partially purified enzyme of gsc1::URA3 cells
      were significantly lower than those of the wild-type and gsc2::LEU2 cells.

PMID- 7649186
TI  - Characterisation of taurochenodeoxycholic acid 6 alpha-hydroxylase from pig liver
      microsomes.
AB  - A fraction of cytochrome P-450 catalysing an efficient 6 alpha-hydroxylation of
      taurine-conjugated 3 alpha,7 alpha-dihydroxy-5 beta- cholanoic acid
      (taurochenodeoxycholic acid) was partially purified from pig liver microsomes.
      The specific content of cytochrome P-450 was 6 nmol/mg protein and the
      preparation showed two major protein bands upon SDS/PAGE. These two bands were
      isolated after SDS/PAGE and protein blotting. The protein band with a molecular
      mass of 53 kDa had an N-terminal amino acid sequence and internal sequences
      resembling that of the cytochrome P-450 4A subfamily (CYP 4A). Polyclonal
      antibodies raised against this protein were able to, after SDS/PAGE and
      immunoblotting, detect the protein in microsomal fractions as well as in the
      purified cytochrome P-450 fraction. Furthermore, addition of these antibodies to
      a reconstituted system containing the cytochrome P-450 fraction, inhibited 6
      alpha-hydroxylation of taurochenodeoxycholic acid by up to 90%. Experiments with
      irrelevant antibodies did not show inhibition of 6 alpha-hydroxylation. The
      purified cytochrome P-450 fraction catalysed in addition omega- and omega-1
      hydroxylation of lauric acid and 6 alpha-hydroxylation of 3 alpha-hydroxy-5 beta
      cholanoic acid (lithocholic acid). However, these hydroxylase activities were
      rather low compared to 6 beta-hydroxylation of taurochenodexycholic acid. The
      enzyme fraction did not show hydroxylase activities towards cholesterol and 5
      beta-cholestane-3 alpha,7 alpha-diol. These results indicate that 6 alpha
      hydroxylation of taurochenodeoxycholic acid is catalysed by a specific species of
      cytochrome P-450 that, according to N-terminal amino acid sequence as well as
      catalytic properties, could be a member of the CYP 4A subfamily.

PMID- 7649187
TI  - Characterization of blood-group-ABO(H)-active glycosphingolipids in type-AB human
      erythrocytes.
AB  - Neutral glycolipids in Folch's upper phase were isolated from human erythrocyte
      membranes of 22 individuals with blood type AB. On immunostaining by TLC with
      anti-A IgG, all reactive glycolipids in type A corresponded to reactive
      glycolipids in type-AB erythrocytes. With anti-B IgM, all reactive glycolipids in
      type-B erythrocytes also corresponded to reactive glycolipids in type-AB
      erythrocytes. By comparison of the reactivity to that of the anti-A and anti-B
      antibodies, it was found that, in type-AB erythrocytes, all glycolipids reactive
      with either one of the anti-A or anti-B antibodies were detected in both type-A
      and type-B erythrocytes, and that A-active glycolipids had higher Rf values than
      B-active glycolipids on TLC plates. A series of glycolipids reactive with both
      antibodies were purified from the Folch's upper neutral glycolipid fraction of
      erythrocyte membranes by column chromatography, and was characterized by TLC
      immunostaining and negative secondary-ion mass spectrometry. The results strongly
      suggested that A-active and B-active carbohydrate chain epitopes existed
      separately as glycolipid molecules in blood-type-AB erythrocytes. It was also
      confirmed that these phenotypes observed in erythrocyte membranes were exhibited
      by blood-group-active glycosphingolipids in the small intestine of blood-type-AB
      individuals. Furthermore, upon treatment of fractions obtained from silicic acid
      column chromatography with alpha-N-acetylhexosaminidase or alpha-galactosidase, a
      branched hybrid-type molecule with both A and B determinants was not detected.

PMID- 7649188
TI  - Multivariate approach to differential diagnosis of acute meningitis.
AB  - A previously reported statistical model based on a combination of four parameters
      (total polymorphonuclear cell count in cerebrospinal fluid (CSF), CSF/blood
      glucose ratio, age and month of onset) appeared effective in differentiating
      acute viral meningitis (AVM) from acute bacterial meningitis (ABM). The
      objectives of this study were to validate this model on a large independent
      sample of patients with acute meningitis and to build and validate a new model
      based on this sample. Of 500 consecutive cases of community-acquired meningitis
      reviewed retrospectively, 115 were ABM, 283 were AVM and 102 were of uncertain
      etiology. For each of the ABM and AVM cases, the probability of ABM versus AVM
      (pABM) was calculated for both models. Sensitivity, specificity and predictive
      values as well as areas under the receiver operating characteristic (ROC) curves
      were calculated for both models. The original model proved an accurate and
      reliable diagnostic test. Its area under the ROC curve was 0.981. For pABM = 0.1,
      its negative and positive predictive values were 0.99 and 0.68, respectively. The
      new model retained four slightly different independent variables: CSF protein
      level, total CSF polymorphonuclear cell count, blood glucose level and leukocyte
      count. Its area under the ROC curve was 0.991 and, for pABM = 0.1, its negative
      and positive predictive values were 0.99 and 0.85, respectively. In conclusion,
      both models provide a valuable aid in differentiating AVM from ABM. They should
      be further evaluated in a prospective appraisal of their contribution to
      therapeutic decision making.

PMID- 7649189
TI  - Prevalence and antibiotic sensitivity of Danish versus other European bacterial
      isolates from intensive care and hematology/oncology units.
AB  - The prevalence and antibiotic sensitivity patterns of bacteria collected
      consecutively from medical and surgical intensive care units (ICUs) and from
      hematology/oncology units in nine hospitals in Denmark were determined and
      compared to data collected simultaneously in 12 other European countries.
      Bacterial isolates from 794 Danish patients were tested and compared to 8,625
      isolates from European patients. The minimal inhibitory concentrations of eight
      different antibiotics were determined using a microdilution plate. Similar to
      findings in European countries, the most common source of bacterial isolates in
      Danish units was the respiratory tract (49%), followed by blood (18%), urinary
      tract (14%) and surgical wounds (10%). Staphylococcus aureus was the most
      prevalent respiratory organism in Danish units, whereas Enterobacteriaceae and
      Pseudomonas aeruginosa dominated in other countries. In blood, Escherichia coli
      was most prevalent in Denmark while coagulase-negative staphylococci were
      predominant in other countries. Urinary tract isolates were dominated by
      Escherichia coli in both Denmark and the other countries, but Enterococcus
      faecalis and Pseudomonas aeruginosa were more frequently isolated in the other
      countries. Staphylococcus aureus was the most frequent wound isolate in Denmark,
      while Enterobacteriaceae other than Escherichia coli dominated in other European
      countries. Thus, in Denmark Escherichia coli and Staphylococcus aureus, followed
      by Pseudomonas aeruginosa and Klebsiella spp. (from ICUs) or Enterococcus spp.
      and Klebsiella spp. (from hematology/oncology units), are the most prominent
      pathogens in these units today. Indicator organisms of antibiotic consumption
      (Pseudomonas aeruginosa and methicillin-resistant coagulase-negative
      staphylococci and Staphylococcus aureus) were more frequent in other European
      countries than Denmark. In general the Danish isolates were more sensitive to
      antibiotics than the European isolates.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7649190
TI  - Variation and persistence of methicillin-resistant Staphylococcus aureus strains
      among individual patients over extended periods of time.
AB  - To determine the strain variation and persistence among isolates of methicillin
      resistant Staphylococcus aureus (MRSA) cultured from patients with colonization
      over extended time spans, pulsed-field gel electrophoresis was used to analyze
      the isolates from 47 patients for whom at least two mecA-positive isolates
      collected a minimum of six months apart were available. For 22 (47%) patients,
      the isolates represented multiple distinct strains of Staphylococcus aureus,
      while 20 (43%) patients had only a single strain detected; five (11%) patients
      had similar, genetically related isolates. MRSA were frequently associated with
      mucocutaneous abnormalities; 29 (62%) patients had focal cutaneous defects, and
      ten (21%) had chronic dermatitis. Multiple strains of MRSA were detected more
      frequently than single strains among patients in whom the initial focus of MRSA
      resolved clinically and another mucocutaneous defect subsequently developed
      compared to patients with clinically persistent foci (11/15 versus 9/23,
      respectively; p = 0.05, Fisher's exact test). Among the 21 patients in this
      series for whom isolates cultured within a two-month time span were available,
      there were seven (33%) patients with multiple strains of MRSA, including one
      patient with polyclonal bacteremia. In summary, patients with long-term MRSA
      colonization often have several different strains of MRSA, which typically change
      overtime in association with removal or resolution of a colonized focus and the
      recurrence of mucocutaneous defects.

PMID- 7649191
TI  - Correlation between activity of beta-lactam agents in vitro and bacteriological
      outcome in acute pulmonary exacerbations of cystic fibrosis.
AB  - A study was conducted to determine whether a direct relationship exists between
      beta-lactam and/or aminoglycoside activity measured in vitro and bacteriological
      outcome in acute pulmonary exacerbations of cystic fibrosis. Twenty-seven
      patients, aged between 6 months and 24 years (mean age 10 1/2 years), were
      included in the study and received 41 i.v. courses of a beta-lactam agent
      combined with an aminoglycoside. A total of 63 Pseudomonas aeruginosa strains
      were found in sputum taken on admission at densities exceeding 10(6) cfu/g of
      sputum. For each episode, the serum inhibitory quotient (SIQ) and the serum
      bactericidal quotient (SBQ) of the beta-lactam agent and of the aminoglycoside
      administered were determined for the Pseudomonas aeruginosa isolate(s). The SIQs
      and SBQs were calculated by dividing the average peak serum levels achievable in
      the patients by the minimal inhibitory concentrations and minimal bactericidal
      concentrations, respectively. The SIQs and SBQs were compared to bacteriological
      outcome. Bacteriological success was defined as a decrease of 2 log10 counts or
      more in the Pseudomonas aeruginosa density in sputum between days 0 and 7 of
      therapy. The SIQ and SBQ of beta-lactam agents were good predictors of
      bacteriological outcome: SIQs of < 1:16 were 100% predictive of failure (chi 2
      28; p < 0.001) and of > or = 1:64 were 92.9% predictive of success (chi 2 35.68;
      p < 0.001); SBQs of < 1:8 were 100% predictive of failure (chi 2 42.78; p <
      0.001) and of > or = 1:32 were 95.8% predictive of success (chi 2 31.5; p <
      0.001). Aminoglycoside SIQs and SBQs were not predictive of outcome.

PMID- 7649192
TI  - Lack of serotype-specific antibody response to lipopolysaccharide antigens of
      Moraxella catarrhalis during lower respiratory tract infection.
AB  - An enzyme immunoassay (EIA) was used to determine the antibody response to
      different serotypes of lipopolysaccharide (LPS) antigens of Moraxella catarrhalis
      in adult patients with lower respiratory tract infections (LRTI). Moraxella
      catarrhalis was isolated from sputum or nasopharyngeal samples from 20 patients
      with LRTI. Sixteen of the isolates were serotype A, four were type B and none
      were type C. The antibody response to the different LPS serotypes was determined
      in paired sera from patients suffering from LRTI. In addition to the 20 patients
      with Moraxella catarrhalis isolated (Group 1), a group of seven patients with
      LRTI of unknown etiology (Group 2) and a group of ten patients with LRTI of known
      other bacterial etiology (Group 3) were selected for this study. An increase in
      antibody levels of > 1.5-fold (convalescent-/acute-phase serum) was recorded in
      approximately half of the patients, not only in the first group (Moraxella
      catarrhalis isolated) but also in the other two groups. However, in the first and
      second groups there was a correlation between an increase in antibody levels in
      the LPS EIA and in an EIA using whole bacterial cells as antigen. In the group of
      patients in whom Moraxella catarrhalis was isolated, the antibody response to LPS
      antigens was not serotype specific. The antibody response to type-A and type-B
      LPS was more predominant than the response to type-C LPS in most
      patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7649194
TI  - Comparison of three monoclonal antibody-based enzyme immunoassays for detection
      of herpes simplex virus in clinical specimens.
AB  - Three commercial monoclonal antibody-based enzyme immunoassays (Herpchek, IDEIA
      HSV and SureCell HSV) for detection of herpes simplex virus antigen were compared
      with isolation of virus in cell cultures. A total of 51 culture positive and 49
      culture negative consecutively collected specimens that had been stored at -70
      degrees C for a period of up to ten months were used in the study. Herpchek,
      IDEIA HSV and SureCell HSV assays gave a sensitivity of 88.2%, 82.4% and 47.1%
      respectively, and a specificity of 95.9%, 93.9% and 83.7% respectively compared
      to cell culture. A blocking antibody test showed that two culture negative
      specimens contained herpes simplex virus-specific antigens. If these two
      specimens were considered to be true positive, Herpchek, IDEIA HSV and SureCell
      HSV assays had a sensitivity of 88.7%, 83.0% and 47.2%, and a specificity of
      100%, 97.9% and 85.1% respectively. The positive predictive value (using the
      resolved sample results) for Herpchek, IDEIA HSV and SureCell HSV was 100%, 97.8%
      and 78.1% respectively, and the negative predictive value 88.7%, 83.6% and 58.8%
      respectively. These results demonstrated that Herpchek and IDEIA HSV are
      sensitive and highly specific assays. Results could be obtained in less than five
      hours after receipt of specimens. SureCell HSV gave results in 15 minutes, but
      both the sensitivity and specificity were too low for this test to be considered
      as a substitute for culture.

PMID- 7649193
TI  - Seroprevalence of hantavirus antibodies in Germany as determined by a new
      recombinant enzyme immunoassay.
AB  - In order to elucidate the epidemiological importance of hemorrhagic fever with
      renal syndrome in Germany, the prevalence of antibodies against hantaviruses was
      determined in 13,358 sera from residents of various geographic regions, 1,284
      sera from occupational risk groups and 287 sera from chronic hemodialysis
      patients. Serological investigations were performed using a highly specific
      transferable solid phase enzyme immunoassay based on the recombinant nucleocapsid
      proteins of a Hantaan and a Puumala serotype strain. The overall antibody
      prevalence was found to be 1.68%. In the serum panels from western and southern
      Germany, it was determined to be 1.83% on average in contrast to only 0.8% in the
      panel from eastern Germany. An endemic focus revealing an antibody prevalence of
      3.12% was detected in a low-mountain area called Suebian Alb, which is located in
      the federal state of Baden-Wurttemberg. Occupational risk groups and a group of
      chronic hemodialysis patients showed a significantly elevated antibody prevalence
      ranging from 3.3% to 10%. The Puumala serotype was found to be the prevailing
      virus, but the percentage of sera predominantly recognizing the Hantaan
      nucleocapsid protein increased towards the south and the east and was
      significantly elevated in dialysis patients.

PMID- 7649195
TI  - Comparative activity of selected antiviral compounds against clinical isolates of
      varicella-zoster virus.
AB  - Sixteen freshly isolated varicella-zoster virus (VZV) strains were evaluated in
      vitro, in parallel with two reference strains expressing a functional thymidine
      kinase (TK+) (Oka and YS) and two thymidine kinase-deficient mutants (TK-) (07-1
      and YS-R), for their susceptibility to a broad range of antiviral compounds. The
      following compounds were included: acyclovir (ACV), brivudine (BVDU), sorivudine
      (BVaraU), other BVDU congeners such as BTDU, CTDU, CVDC and CVDU, ganciclovir
      (GCV), FIAC, araT, araA, araC, foscarnet (PFA), phosphonoacetic acid (PAA), the
      acyclic nucleoside phosphonates HPMPC, cHPMPC, HPMPA, cHPMPA, HPMPc3A, PMEA and
      PMEDAP, the N7-isomeric acyclic nucleoside analogue N7AP, penciclovir (PCV),
      compounds 882C87 and H2G and two oxetanocin derivatives OXT-A and OXT-G. Fourteen
      of the 16 clinical isolates displayed the following order of decreasing
      selectivity against VZV: BVaraU > BVDU > CVDU approximately CVDC > H2G > N7AP
      approximately CTDU approximately BTDU approximately OXT-G approximately 882C87 >
      ACV > FIAC approximately araT > HPMPC approximately cHPMPC approximately HPMPA
      approximately HPMPc3A approximately cHPMPA > PCV approximately GCV approximately
      OXT-A > PMEDAP approximately PMEA > PFA approximately PAA approximately araA >
      araC. Two VZV strains (isolated from the cerebrospinal fluid of an AIDS patient)
      that were shown to have a truncated TK were clearly resistant to all the
      compounds that need the viral TK for their phosphorylation, while sensitivity to
      the acyclic nucleoside phosphonates, PFA, PAA, OXT-A and araA, remained
      unchanged. A slight (5- and 10-fold) increase was noted in the 50% inhibitory
      concentration of N7AP and OXT-G, respectively, for the TK- VZV strains as
      compared to the TK+ VZV strains. Ganciclovir and FIAC also showed a marked
      decrease in their activity against these two strains, but this was not as
      pronounced as for the other viral TK-dependent drugs. From our results, it
      appears that although acyclic nucleoside phosphonates may not have as favourable
      a therapeutic index as drugs requiring the viral TK, they should be considered
      for the treatment of TK- VZV life-threatening infections that are resistant to
      the viral TK-dependent drugs.

PMID- 7649196
TI  - Comparison of two assays for detection of HIV antibodies in saliva.
AB  - The presence of HIV antibodies was screened in 241 paired samples of serum and
      saliva from seronegative subjects with risk factors for human immune deficiency
      virus (HIV) infection (n = 99), asymptomatic and symptomatic HIV-seropositive
      patients (n = 104) and healthy blood donors (n = 38) as negative controls, in
      order to assess the reliability of two saliva tests for the detection of HIV
      antibodies. These results were confirmed by Western blot. The saliva samples were
      collected using an oral device (Salivette) maintained in the lateral gingival
      fold until the individual perceived that it was becoming less rigid due to
      hydration with saliva. The two tests were a rapid one (Test Pack) and a
      conventional one (GACELISA). The results for antibody detection in saliva show
      99% specificity and 99% sensitivity for the rapid test versus 100% sensitivity
      and 81% specificity for the conventional test. All results for the saliva samples
      which were positive in the rapid test were confirmed by Western blot (WHO
      criteria), and there were no indeterminate Western blot results among the samples
      which were false-positive in the conventional enzyme immunoassay. No
      statistically significant differences were observed between the absorbance values
      of HIV-infected symptomatic and asymptomatic patients. The correlation for the
      results of the HIV-antibody analysis in the paired sera was 98%. This method of
      saliva sampling in combination with a rapid and sensitive test for HIV-antibody
      detection may be applicable in studies conducted with limited technical resources
      or insufficiently trained health personnel or where blood sample collection is
      difficult.

PMID- 7649197
TI  - Disseminated Nocardia transvalensis infection resembling pulmonary infarction in
      a liver transplant recipient.
AB  - Infections due to Nocardia transvalensis are extremely rare: only four
      disseminated infections with this pathogen have been reported, three of which
      ended fatally. This is the first report of a liver transplant recipient with
      Nocardia transvalensis infection. The patient had disseminated infection with
      pulmonary involvement, which presented as pulmonary infarction. Despite a ten-day
      delay in the administration of correct therapy, he responded rapidly to
      trimethoprim-sulfamethoxazole. The pitfalls of differentiating nocardial
      infection from pulmonary thromboembolism in solid organ transplant recipients and
      the diagnostic considerations unique to liver transplant recipients are
      discussed.

PMID- 7649198
TI  - Failure of pristinamycin treatment in a case of pneumococcal pneumonia.
AB  - A case of pneumonia caused by Streptococcus pneumoniae occurring in a patient
      receiving pristinamycin is reported. Despite empirical treatment with
      pristinamycin, 2 g/day for five days, the patient's condition worsened. Protected
      brush specimen and blood cultures permitted isolation of Streptococcus
      pneumoniae. MIC testing indicated that the strain was susceptible to
      pristinamycin and resistant to erythromycin and penicillin. Streptococcus
      pneumoniae was eradicated by cefotaxime, and pneumonia resolved. This case
      underlines the fact that pristinamycin may not be suitable for the treatment of
      multiresistant pneumococcal infections.

PMID- 7649199
TI  - Use of ribotyping to investigate tracheal colonisation by Staphylococcus
      epidermidis as a source of bacteremia in ventilated newborns.
AB  - Ribotyping was used to determine whether a relationship exists between
      endotracheal tube colonisation with Staphylococcus epidermidis and bacteremia
      with this organism. Over a three-week period, four mechanically ventilated
      preterm babies presented with five episodes of infection and bacteremia. For each
      blood specimen obtained for culture a tracheal aspirate sample was collected at
      the same time by suctioning. After DNA extraction and cleavage by EcoRI,
      hybridisation was performed with a digoxigenin-labelled 16S-rDNA probe from
      Escherichia coli. Five different band patterns were recognised on the membrane.
      In two children the same band pattern was found in Staphylococcus epidermidis
      isolated from both blood and tracheal aspirate. Ribotyping thus could be used to
      differentiate a series of infections from an outbreak and showed that a
      relationship may exist between tracheal colonisation and bacteremia in
      mechanically ventilated newborns.

PMID- 7649200
TI  - Value of routine stool cultures in hospitalized patients with diarrhea.
AB  - In a prospective study conducted over a six-month period, the relative yield of
      721 routine cultures of stool from adult inpatients as a function of the time
      after hospital admission was assessed. Salmonella, Campylobacter, Shigella or
      Yersinia spp. were recovered from 10.9% (41/377) of patients within three days of
      hospitalization and from only 1.5% (5/344) after three days. However, a review of
      these patients' charts did not suggest nosocomial transmission but rather a delay
      in stool collection or asymptomatic carriage. Clostridium difficile was isolated
      with a high frequency in patients both within and after three days of
      hospitalization (10.3% and 10.2%, respectively). Thus, stool specimens from
      adults hospitalized for more than three days should not be cultured except for
      Clostridium difficile unless there are plausible clinical or epidemiological
      reasons to do so.

PMID- 7649201
TI  - Transport and storage of Helicobacter pylori from gastric mucosal biopsies and
      clinical isolates.
AB  - Various transport and storage conditions for the recovery of Helicobacter pylori
      from gastric biopsies were evaluated. Gastric mucosal biopsies from 16
      Helicobacter pylori-infected patients were stored in cysteine-Albimi medium
      containing 20% glycerol in a refrigerator (4 degrees C) for 1 and 2 weeks and in
      a -20 degrees C laboratory freezer for 4 and 12 weeks. Two clinical isolates were
      stored in saline, Stuart's transport media, cysteine-Albimi broth with 20%
      glycerol, brucella broth with 20% glycerol and skim milk with 17% glycerol at
      room temperature, 4 degrees C, -20 degrees C and -70 degrees C. Storage at 4
      degrees C for 1 and 2 weeks resulted in Helicobacter pylori recovery from 81% and
      19% of biopsies, respectively. Storage at -20 degrees C yielded Helicobacter
      pylori recovery in 100% and 57% after 4 and 12 weeks, respectively. At room
      temperature after 6 h, the Helicobacter pylori titer was reduced. The best
      storage media for frozen isolates were skim milk/glycerol, brucella
      broth/glycerol and cysteine-Albimi/glycerol (in descending order). Recovery was
      better at -70 degrees C than -20 degrees C.

PMID- 7649202
TI  - Effect of an acidic environment on the susceptibility of Helicobacter pylori to
      trospectomycin and other antimicrobial agents.
AB  - The susceptibility of 30 clinical isolates of Helicobacter pylori to
      trospectomycin, ampicillin, metronidazole, clarithromycin, azithromycin and
      clindamycin under varying pH conditions was evaluated. An acidic environment was
      shown to affect unfavourably the activity of all the antimicrobial agents tested.
      This pH effect was most marked for the two macrolides and for clindamycin.

PMID- 7649203
TI  - Rapid detection of Campylobacter jejuni and Campylobacter coli isolated from
      clinical specimens using the polymerase chain reaction.
AB  - Seventeen Campylobacter strains isolated from 16 children hospitalised with acute
      diarrhea were analysed by in vitro enzymatic amplification using two sets of
      oligonucleotide primers specific for Campylobacter jejuni and Campylobacter coli,
      respectively. Thirteen strains (76%) were identified as Campylobacter jejuni and
      four strains (24%) as Campylobacter coli. Subsequent bacteriological
      identification confirmed the identity of the same 13 Campylobacter jejuni strains
      and the 4 Campylobacter coli strains. Thus, these PCR methods enabled rapid and
      specific detection of all the Campylobacter jejuni and Campylobacter coli strains
      without any false-positive or false-negative results.

PMID- 7649204
TI  - Influence of the incubation atmosphere on the production of slime by
      Staphylococcus epidermidis.
AB  - The influence of various incubation atmospheres on the growth and slime
      production of 23 Staphylococcus epidermidis strains was studied. The atmospheres
      evaluated were aerobiosis (control), anaerobiosis, candle jar, 5% CO2 and 10%
      CO2. As compared to the aerobic control, growth was 55.7 +/- 19% (p < 0.01) in
      anaerobic incubation, 113.7 +/- 12% (p < 0.01) in 5% CO2, 112.8 +/- 13% (p <
      0.01) in 10% CO2 and 106.4 +/- 7% (p > 0.1) in the candle jar. The slime
      production in relation to the aerobic control was 20.3 +/- 19% in anaerobiosis (p
      < 0.01), 22.3 +/- 27% (p < 0.01) in 5% CO2, 29.4 +/- 39% (p < 0.01) in 10% CO2
      and 68.3 +/- 26% (p > 0.1) in the candle jar. The results of this study may
      explain the discrepancies which have been noted on occasion between slime
      formation data and pathogenicity.

PMID- 7649205
TI  - In vitro activity of amphotericin B, flucytosine and fluconazole against yeasts
      causing bloodstream infections.
AB  - The in vitro activity of amphotericin B, flucytosine and fluconazole against 95
      yeasts causing fungemia in a single institution over the last eight years was
      determined by a broth macromethod recommended by the National Committee for
      Clinical Laboratory Standards. All strains were inhibited by amphotericin B
      concentrations of < or = 1 microgram/ml. With flucytosine in most species the
      MIC50 was between 0.12 and 0.25 microgram/ml and the MIC90 was between 0.25 and 1
      microgram/ml. One exception with flucytosine was Candida krusei, with an MIC50
      and MIC90 of 16 micrograms/ml and 32 micrograms/ml, respectively. Overall, 12% of
      the isolates needed at least 8 micrograms/ml of fluconazole to be inhibited.
      Fluconazole was very active against Candida albicans, Candida tropicalis and
      Cryptococcus neoformans, with MIC50 ranging from 0.12 to 0.5 microgram/ml and
      MIC90 of 1 microgram/ml, and somewhat less active against Candida parapsilosis
      (MIC50 of 1 microgram/ml and MIC90 of 4 micrograms/ml). Fluconazole exhibited
      poor in vitro activity against Candida krusei (MIC50 and MIC90 of 64
      micrograms/ml) and Torulopsis glabrata (MIC50 of 4 micrograms/ml and MIC90 of 16
      micrograms/ml). High MICs of fluconazole were found for four strains of Candida
      albicans, one with an MIC of 4 micrograms/ml and three (5.7%) with MICs of > or =
      16 micrograms/ml. Previous exposure to fluconazole could be demonstrated in two
      of these strains. Further work must be done in order to determine appropriate
      breakpoints of antifungal agents, to assess the clinical relevance of azole
      resistance in yeasts causing bloodstream infections and to identify risk factors
      for infections with azole-resistant yeasts.

PMID- 7649206
TI  - Staphylococcal brain abscess following hematogenous seeding of an intracerebral
      hematoma.

PMID- 7649207
TI  - Partial orthotopic liver transplantation in rats.
AB  - A partial orthotopic liver transplantation technique (70% POLT) for use in rats
      and comparable with the corresponding recipient operation in the 'splitting
      transplantation' in man was developed. Body weight, liver function, histological
      and electron-microscopic findings were studied in comparison with whole rat liver
      transplantation with rearterialization, 30% POLT and corresponding liver
      resections. After 70 and 30% POLT typical signs of hepatic regeneration were
      found, but no pathological alterations in the electron-microscopic picture. This
      POLT model might be helpful for the investigation of unresolved questions in
      'splitting transplantation'.

PMID- 7649208
TI  - Inhibition of macrophage procoagulant activity with lipids reduces intra
      abdominal abscess formation in mice.
AB  - Macrophage procoagulant activity (PCA) has been proposed as a critical element in
      the formation of intra-abdominal abscesses. We tested the ability of local and
      systemic lipids (a known PCA inhibitor in vitro) to alter both peritoneal
      macrophage PCA and mixed Escherichia coli/Bacteroides fragilis intra-abdominal
      abscess formation in vivo. Lipids given intraperitoneally inhibited measured
      inducible peritoneal macrophage PCA for 8 h, and, in other animals, significantly
      decreased the number of abscesses formed and prevented abscesses in 29% of
      animals. Parallel experiments using subcutaneous intralipids did not show these
      effects. These results support the hypothesis that macrophage PCA produced
      locally is critical for intraperitoneal abscess formation.

PMID- 7649209
TI  - Modulation of muscle protein metabolism in disseminated intravascular
      coagulation.
AB  - Muscle protein degradation and intracellular protease activities were
      investigated in disseminated intravascular coagulation (DIC), which is frequently
      associated with severe catabolic states such as sepsis and multiple organ
      failure. DIC was introduced in rats by repeated intravenous thrombin injections.
      Saline was injected in control rats. In the 28 rats (14 with DIC and 14
      controls), the bilateral soleus (SOL) muscles were incubated in an oxygenated
      medium without cycloheximide (CH) to determine the release of tyrosine (Tyr) into
      the incubated medium. From 24 rats (12 with DIC and 12 controls), the SOL and
      extensor digitorum longus (EDL) muscles were harvested to measure the activities
      of proteasome and of cathepsins L and B. The contralateral muscles were incubated
      in a medium with 0.5 mM CH to determine the release of Tyr and 3-methylhistidine
      (3-MH). The release of Tyr without CH (net proteolysis) from SOL muscles with DIC
      was greater than in controls (218 +/- 83.3 vs. 145 +/- 47.7 pmol/mg/h. However,
      the release of Tyr and 3-MH with CH (total proteolysis) and the activities of
      proteasome and cathepsins in DIC were nearly the same as those in controls. In
      both DIC and control rats, the total release of Tyr and proteasome activity were
      greater in SOL than in EDL muscles. These results suggest that reutilization of
      Tyr, reflecting protein synthesis, is suppressed in DIC and that the red slow
      muscle is more active in nonfibrillar proteolysis than the white fast muscle.

PMID- 7649210
TI  - Comparison of warm and cold ischemia of the canine small intestine.
AB  - Warm and cold ischemia-reperfusion injuries to canine small intestine was
      compared. In the warm ischemic model, the superior mesenteric artery of mongrel
      dogs was clamped for 2 h and then released (group A). As a cold ischemia model,
      canine small intestines were harvested with cold lactated Ringer solution,
      preserved for 24 h in cold LR solution and then autotransplanted (group B). After
      ischemia and during reperfusion, activities of maltase (MAL), myeloperoxides
      (MPO), xanthine dehydrogenase (XD) and xanthine oxidase (XO) were measured as
      well as hypoxanthine (HX) concentration. MAL activities were not changed during
      warm or cold ischemia, whereas it was remarkably decreased after
      revascularization in both the groups. Neutrophil infiltration after reperfusion
      was shown by the increase of MPO activities to 8 and 1.5 U/mg protein in groups A
      and B respectively from a normal value of 0.35 U/mg protein. During warm
      ischemia, %XO (XO/XD + XO) was increased from 18.4 to 84.9% for 2 h. In contrast,
      %XO was not changed for 24 h of cold ischemia. Tissue accumulation of HX was
      increased 2.8 times from a normal value of 1.06, 2 h after warm ischemia, but
      there was almost neither accumulation of HX nor the conversion of XD to XO in 24
      h cold ischemia. It was observed that warm and cold ischemia caused similar
      injury after reperfusion in spite of the striking difference in the conversion of
      XD to XO and accumulation of HX. Thus, it is suggested that the XO system is not
      always necessary for ischemia-reperfusion injury.

PMID- 7649211
TI  - Decreased energy charge of peripheral blood lymphocytes in septic patients after
      hepatic resection.
AB  - We measured lymphocyte energy charge (LEC) in septic patients after hepatectomy
      to clarify the energy metabolism of lymphocytes in relation to arterial ketone
      body ratio (AKBR) reflecting the hepatic mitochondrial redox potential. Sixteen
      patients with AKBR above 0.7 (state A) tolerated their operations well without
      postoperative infectious episodes and their LEC (0.895 +/- 0.005, mean +/- SEM)
      was significantly (p < 0.001) higher than that (0.841 +/- 0.010) of 9 patients
      with AKBR from 0.7 to 0.4 (state B). Four of the 9 state B patients had multiple
      organ failure (MOF) with sepsis as a trigger. AKBR in 7 of 9 state B patients
      decreased and remained below 0.4 (state C). These state C patients showed
      significantly reduced LEC (0.781 +/- 0.024; p < 0.001, p < 0.05, compared with
      that in states A and B, respectively) and finally died of MOF with septic state.
      These results suggest that the severe and prolonged impairment of energy
      metabolism in the liver may be accompanied with the metabolic derangement of
      lymphocytes.

PMID- 7649212
TI  - Impaired wound healing but unaltered colonic healing with increasing age: an
      experimental study in rats.
AB  - Age-related differences in the healing of left colonic anastomoses and abdominal
      incisional wounds were compared between young and old rats. Immediately after
      surgery the anastomotic strength (suture-binding capacity) was 67% higher in old
      rats corresponding to a 107% higher collagen content per unit length of left
      colon compared to young rats. After 2 and 4 days of healing there was no
      difference in the breaking strength of the anastomoses between young and old
      rats, although the increase in collagen content of the anastomosed segment was
      100% in the young rats and only 35% in the old rats from day 2 to day 4. The
      healing of the abdominal incisional wounds was, however, impaired in old rats
      compared to young rats, since the tensile strength and the energy absorption on
      the 4th postoperative day was 67 and 57% lower, respectively. In conclusion, old
      rats have impaired skin healing, whereas colonic healing is not affected by age.

PMID- 7649213
TI  - Morphological and functional characteristics of tumor-infiltrating lymphocytes
      from human colorectal cancers after stimulation with rIL-2.
AB  - Tumor-infiltrating lymphocytes (TILs) from colorectal cancers were separated from
      tumor cells by enzymatic and mechanical tissue disaggregation and discontinuous
      density gradients. Peripheral blood lymphocytes (PBLs) were isolated using the
      same procedure. The freshly separated TILs and PBLs were analyzed phenotypically
      by flow cytometry. The CD4+/CD8+ ratios of the freshly isolated TILs and PBLs
      were comparable (> 1 in both lymphocyte populations). CD25+, HLA-DR+ and CD56+
      cells were significantly more frequent in the TIL than in the PBL population.
      However, the number of CD45RA+ cells was lower in the TILs as compared to PBLs,
      while CD29+ accumulated by about 90% in TILs. TILs and autologous PBLs were
      expanded in vitro with rIL-2. The mean rate of proliferation after 4 weeks was
      642-fold in TIL cultures and 335-fold in PBLs. More than 90% of the rIL-2
      expanded lymphocytes expressed CD2 and the great majority was CD29+. Stimulation
      with rIL-2 in vitro induced an outgrowth of CD56+ cells mainly in the TILs.
      Accordingly the expression of CD3+ and alpha/beta receptor in the TILs was low.
      Those cells which phenotypically represented lymphokine-activated killer cells
      displayed a lytic activity against the autologous tumor as well as against
      allogeneic K562 and Daudi targets. In accordance with the better proliferative
      response of TILs in long-term cultures with rIL-2, the lytic activity of TILs
      against autologous and allogeneic tumor targets was significantly higher as
      compared to PBLs.

PMID- 7649214
TI  - Control of myocardial reperfusion injury with hypertonic-hyperosmotic solution in
      isolated rabbit heart.
AB  - The effects of postischemic reperfusion were investigated in 14 isolated rabbit
      hearts in Langendorff preparation. Seven were controls and the others were
      reperfused with a sodium 7.5% and dextran 60 (60,000 MW) solution diluted with
      Krebs-Henseleit buffer to a sodium concentration of 150 mEq/l. The incidence of
      arrhythmias was lower in this group (p = 0.034). Coronary flow was higher than in
      controls (p = 0.035), the levels of isoenzyme MB of creatine kinase were lower
      than in controls (p = 0.035), myocardial water content was also lower (p =
      0.047), and histological damage was reduced (p = 0.018). It was concluded that
      early reperfusion with 7.5% sodium chloride, 6% dextran 60 solution has a
      protective effect in the treatment of cardiac reperfusion injury.

PMID- 7649215
TI  - Closed fracture healing: a rat model.
AB  - A rat model for the study of closed fracture healing is described. Standard
      closed tibial fractures were produced with specially designed pliers in 24 rats.
      All fractures were located in the middle third of the tibia and healed without
      complications as delayed union, infection or soft tissue problems. The average
      angle of the fracture line with the axis of the tibia on lateral view was 80 +/-
      2 degrees (SEM). The model is considered to be suited for the study of closed
      fracture healing processes. Closed intramedullary fracture fixation, can also be
      evaluated in this model.

PMID- 7649216
TI  - 30th Congress of the European Society for Surgical Research (ESSR). Amsterdam,
      The Netherlands, May 10-13, 1995. Abstracts.

PMID- 7649217
TI  - Cathepsin D from Alzheimer's-diseased and normal brains.
AB  - An acid protease activity from human brain was found to cleave a fluorogenic
      peptide substrate encompassing the amino terminus of Alzheimer's amyloid-beta
      peptide (A beta). The protease was isolated and determined to be cathepsin D
      based on chromatographic, immunological, and enzymatic data. Analysis of the
      cleavage sites indicated that cathepsin D hydrolyzed the methionine--aspartate
      bond generating the in vivo amino terminus of A beta. These data suggested that
      cathepsin D could be involved in amyloidogenic processing of the amyloid
      precursor protein. Consequently, cathepsin D from both Alzheimer's-diseased and
      control brains was compared to determine whether there were any differences which
      could account for an increase in A beta production in Alzheimer's disease. No
      differences were detected in isoform composition or tissue content of cathepsin D
      as measured by 2-D IEF-SDS-PAGE. Enzymological characterization of brain
      cathepsin D demonstrated that it could undergo a previously undescribed pH
      dependent reversible activation. However, that activation appeared identical for
      both AD and normal brain enzymes. These data demonstrate that concentration,
      isoform distribution, and several enzymological characteristics of cathepsin D
      are not distinguishable between AD and normal brain. The pH dependence of
      cathepsin D activity suggests, however, that its intracellular localization may
      be important in considering the potential role of cathepsin D in Alzheimer's
      disease.

PMID- 7649218
TI  - Mechanism of suramin toxicity in stable myelinating dorsal root ganglion
      cultures.
AB  - Suramin is an experimental chemotherapeutic agent which produces a severe dose
      related neuropathy. Suramin inhibits axonal growth from rat dorsal root ganglion
      neurons. This inhibition is dose dependent and reversed by increasing nerve
      growth factor concentrations. In this study, myelinating dorsal root ganglion
      cultures were exposed to various concentrations of suramin and nerve growth
      factor. Effects were assessed with quantitative light and electron microscopy.
      Using a systematic sampling technique, suramin was observed to produce dose and
      time-dependent myelinated fiber degeneration. With 9-day exposure, there was no
      effect with suramin concentrations of 100 microM or less. At 200 microM, 17% of
      the myelinated fibers were degenerating at 4 days and 53.3% by 9 days. At 300
      microM, 72.7% of the myelinated fibers and at 1316 microM, 88.7% of the
      myelinated fibers were degenerating at 4 days. It appeared that secondary
      demyelination was the major process. Large multilamellar inclusion bodies filled
      Schwann cells, particularly those investing unmyelinated fibers and dorsal root
      ganglia neuron cell bodies. The size and frequency of these inclusions increased
      with prolonged exposure to suramin (300 microM). Immunohistochemistry revealed
      that the inclusions were composed primarily of GM1 ganglioside. These effects
      were not influenced by increasing nerve growth factor up to 500 ng/ml. We
      conclude that suramin causes injury to both axons and Schwann cells that is not
      prevented by NGF and produces and experimental form of GM1 gangliosidosis.

PMID- 7649219
TI  - Neuronal injury following electrically induced status epilepticus with and
      without adenosine receptor antagonism.
AB  - Adenosine is thought to act as an endogenous anticonvulsant and neuroprotective
      substance in the brain. In the present study we compared neuronal death following
      status epilepticus (SE) induced in the presence of 8-cyclopentyl-1,3
      dimethylxanthine (8-CPT), an A1-adenosine receptor antagonist, with that
      following SE induced by continuous hippocampal stimulation. Hippocampal damage
      was characterized using selective nerve and nonnerve cell markers. Six days after
      SE, both models produced similar patterns of CA1 and CA3 cell loss and selective
      loss of parvalbumin and hilar somatostatin-immunoreactive interneurons. Calbindin
      D28K-immunoreactive interneuron numbers and calbindin D28K immunoreactivity in
      dentate granule cells remained unchanged although calbindin D28K staining was
      lost in damaged CA1 neurons. Neuronal injury in these areas was also accompanied
      by reactive gliosis and microglial proliferation, as well as the production of
      basic fibroblast growth factor and insulin-like growth factor-1 by astrocytes.
      Although hippocampal damage appeared to be more severe after SE induced in the
      presence of 8-CPT, this may be due to the increased severity of SE generated in
      this model.

PMID- 7649220
TI  - Inhibition of the accelerative effects of testosterone on hamster facial nerve
      regeneration by the antiandrogen flutamide.
AB  - We have previously demonstrated that systemic administration of testosterone
      propionate (TP) to adult hamsters accelerates the rate of facial nerve
      regeneration following crush axotomy of the facial nerve at its exit from the
      stylomastoid foramen. In this study, we utilized flutamide, a potent nonsteroidal
      antiandrogen, in conjunction with radioisotopic labeling procedures for the
      assessment of facial nerve regeneration rates to test the hypothesis that TP
      exerts its accelerative effects on facial nerve regeneration through a receptor
      mediated mechanism. Castrated adult male hamsters were subjected to right facial
      nerve crush axotomies and divided into three groups of axotomized animals:
      castrate plus one subcutaneous TP implant plus daily injections of flutamide,
      castrate plus one subcutaneous TP implant plus vehicle injections, and castrate
      only plus sham implant and vehicle injections. There were two postoperative
      timepoints: 4 and 7 days. In agreement with previous studies, systemic
      administration of TP resulted in an approximately 26% increase in the rate of
      regeneration of the fastest growing population of axons. Exposure to flutamide
      completely abolished the TP-induced accelerative effects on facial nerve
      regeneration rate. As a bioassay for the effectiveness of systemic administration
      of flutamide by subcutaneous injection, seminal vesicle weights were collected
      from all groups at the end of the postoperative time and compared as a percentage
      of the seminal vesicle weights of intact (nongonadectomized) male control
      animals. Castration greatly reduced seminal vesicle weights, whereas exogenous TP
      restored the seminal vesicle weights to those of the intact male. Flutamide
      blocked the effects of exogenous TP on seminal vesicle weights and reduced them
      to castrate levels.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7649221
TI  - Shunt treatment at two postnatal ages in hydrocephalic H-Tx rats quantified using
      MR imaging.
AB  - The H-Tx rat has inherited hydrocephalus with an onset in late gestation.
      Ventriculosubcutaneous shunts were placed in a group of hydrocephalic pups at 3-6
      days after birth and in another group at 8-12 days after birth. Multislice proton
      magnetic resonance (MR) images were taken of shunt-treated pups at 7, 14, or 21
      days and of age-matched control and untreated hydrocephalic rats and were
      subjected to quantitative analysis. Some rats were also imaged before surgery.
      The volume of the ventricles of untreated hydrocephalic pups increased linearly
      with age at a rate of 52 microliters/day. The ventricles of shunted pups were
      reduced from the preshunt condition and were around 20% of age-matched
      hydrocephalic rats. There was no significant difference in the post-shunt volume
      between early and late shunt groups. The cortical mantle thickness in both groups
      of shunt-treated rats was significantly thicker than in untreated pups and close
      to that of control rats. It is concluded that shunt treatment at both ages
      reversed the hydrocephalus as measured from MR images, although other evidence
      from fixed brains suggests that normal morphology may not be achieved at the
      cellular level even for early shunts.

PMID- 7649222
TI  - Evidence that actin depolymerization protects hippocampal neurons against
      excitotoxicity by stabilizing [Ca2+]i.
AB  - Calcium influx through glutamate receptors and voltage-dependent channels
      mediates an array of functional and structural responses in neurons. However,
      unrestrained Ca2+ influx can injure and kill neurons; a mechanism implicated in
      both acute and chronic neurodegenerative disorders. Data reported here indicate
      that depolymerization of actin filaments can stabilize intracellular free calcium
      levels ([Ca2+]i) and protect hippocampal neurons against excitotoxic injury.
      Studies with fluorescein-labeled phalloidin showed that cytochalasin D and
      glutamate each induced actin filament depolymerization. The microfilament
      disrupting agent cytochalasin D protected cultured rat hippocampal neurons
      against glutamate toxicity, whereas the actin filament-stabilizing agent
      jasplakinolide potentiated glutamate toxicity. The microtubule-disrupting agent
      colchicine was ineffective in protecting neurons against glutamate toxicity.
      Cytochalasin D did not protect neurons against calcium ionophore toxicity or iron
      toxicity, indicating that its actions were not due to nonspecific effects on Ca2+
      or free radical metabolism. Cytochalasin D markedly attenuated kainate-induced
      damage to hippocampus of adult rats, suggesting an excitoprotective role for
      actin depolymerization in vivo. Elevations of [Ca2+]i induced by glutamate were
      attenuated in cultured hippocampal neurons pretreated with cytochalasin D and
      potentiated in neurons pretreated with jasplakinolide. The [Ca2+]i response to a
      Ca2+ ionophore was unaffected by cytochalasin D, suggesting that actin
      depolymerization reduced Ca2+ influx through membrane channels. Taken together
      with previous patch clamp data, our findings suggest that depolymerization of
      actin in response to Ca2+ influx may serve as a feedback mechanism to attenuate
      potentially toxic levels of Ca2+ influx.

PMID- 7649224
TI  - The loss of regenerated host axons in nerve allografts after stopping
      immunosuppression with cyclosporin A is related to immune effects on allogeneic
      Schwann cells.
AB  - After immunosuppressive therapy with Cyclosporin A (Cy-A) is stopped, nerve
      allograft rejection occurs. In addition to the loss of allogeneic perineurial,
      vascular, and Schwann cells, host axons that regenerate into the allograft
      disappear despite the fact that the axons are not foreign tissue. The present
      experiment was performed to correlate immune events and allogeneic cell and host
      axonal loss in nerve allografts after terminating Cy-A treatment. Nerve grafts (4
      cm long) were taken from American Cancer Institute (ACI) rats and joined to the
      peroneal nerves of Fischer (FR) or ACI rats that received a daily dose of Cy-A
      (10 mg/kg, intraperitoneally). After one week, Cy-A therapy was stopped and the
      grafts were examined 2-6 weeks postoperatively by light and electron microscopy.
      No immune reaction nor destruction of perineural, vascular, or Schwann cells was
      found in 2- or 3-week-old allografts (i.e., ACI to FR grafts). These grafts
      underwent Wallerian degeneration and were invaded proximally by regenerating host
      axons, some of which were thinly myelinated. At 4 weeks, the perineurium of each
      allograft became infiltrated by mononuclear cells and was destroyed. Many of the
      endoneurial blood vessels of these grafts were occluded and their endothelial
      cells were degenerating or missing. Despite the immune reaction, allogeneic
      Schwann cells remained and continued to myelinate or ensheath host axons that had
      now grown up to 3 cm into the grafts.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7649223
TI  - Possible coordinated gene expressions for FGF receptor, FGF-5, and FGF-2
      following seizures.
AB  - We have examined the influence of afferent activity that may trigger a
      coordinated response between ligands and their signal transduction receptors, as
      part of the regulation of the fibroblast growth factor (FGF) system. Epileptiform
      activity was induced by kainic acid injection, and in situ hybridization was used
      to assess the progress of changes in distribution and intensities of FGF receptor
      1 (FGFR-1), FGF-5, and FGF-2 mRNAs. Our results showed that at early stages (3 h)
      afferent activity triggered a transient increase in both of the ligand mRNAs,
      whereas the receptor mRNA response was increased only in the dentate gyrus. At
      later stages, the FGFR-1 mRNA response was more complex, in which the various
      regions examined exhibited a broader range of values within the same time-points.
      This contrasted with the uniform pattern of FGF-5 and FGF-2 mRNAs responses,
      which in most of the brain regions examined showed a peak by 12 h following
      seizure induction and returned to normal values by 24 h. Immunohistochemistry
      showed an induction of FGFR-1 and FGF-2, 6 h postseizure induction which remained
      elevated up to 24 h later. The distinctive pattern of the FGFR-1 mRNA response
      appears to indicate that FGFR-1 is a factor in the modulation of the cellular
      response for FGF-5 and FGF-2. These results demonstrate that brain activity
      exerts influences at the gene expression levels of FGFR-1 and its ligands FGF-5
      and FGF-2.

PMID- 7649225
TI  - Neuronal apoptosis in an in vitro model of photochemically induced oxidative
      stress.
AB  - In neurons, oxidative stress can be triggered by neurotransmitter-linked
      mechanisms and may lead to apoptotic cell death. A simple and reproducible model
      of inducing oxidative stress is needed to elucidate mechanisms which link
      oxidative stress and neuronal apoptosis. We report here a method of inducing
      apoptosis in cell cultures by loading them with a photosensitive dye, rose
      bengal, and exposing the cultures to light, a procedure which generates reactive
      singlet oxygen. We used this model in primary culture of rat cerebellar granule
      neurons, and in a nonneuronal human embryonic kidney 293 cell line. We have
      measured the following: (a) metabolic activity of the mitochondria by
      quantitative staining with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium
      bromide (MTT), (b) DNA fragmentation by quantitative in situ terminal
      deoxynucleotidyl transferase assay, and (c) cell viability by a trypan blue
      exclusion test. The oxidative stress caused an early impairment of mitochondrial
      function (MTT assay). This was followed by DNA fragmentation and ultimately by
      cell death. Protection was obtained with an inhibitor of macromolecular
      synthesis, anisomycin, and with antioxidant, vitamin E. This model can be used to
      study the mechanism of oxidative stress-triggered neuronal apoptosis, and it may
      help in discovering new targets for neuroprotective drugs.

PMID- 7649226
TI  - DNA fragmentation and immediate early gene expression in rat striatum following
      quinolinic acid administration.
AB  - Excitotoxic cell death is hypothesized to contribute to numerous neuropathologic
      conditions, including hypoxic/ischemic encephalopathy, hypoglycemia, Parkinson's
      disease, and Huntington's disease. Neuronal death from excitotoxic lesions has
      been shown to be an active process, with activation of immediate early gene
      transcription, resulting in secondary changes in gene expression. Another feature
      of neurotoxic cell death that has been examined is the presence of DNA
      fragmentation, which presumably indicates impending nuclear disintegration. A
      technique has been described for labeling fragmented DNA in situ, allowing
      precise determination of the anatomic and temporal distribution of neurons after
      an excitotoxic lesion. To investigate this phenomenon, we performed in situ nick
      translation on brain tissue from rats that have undergone stereotaxically placed
      intrastriatal quinolinic acid injections. Furthermore, in these same animals we
      analyzed the expression of c-fos mRNA to compare the time course and regional
      distribution of DNA fragmentation with immediate early gene activation after an
      excitotoxic lesion. Our analysis indicates that c-fos expression increases soon
      after quinolinic acid injection, is widespread in rat brain, but is effectively
      absent by 24 h postinjection. DNA fragmentation, however, is limited to striatum
      and is maximal at 24 h after injection. These results demonstrate the sensitivity
      of in situ nick translation for the detection of regional neuropathology and
      illustrate the temporal and spatial relationship of c-fos expression to
      excitotoxic neuronal death.

PMID- 7649227
TI  - Suppressed epileptogenesis in BDNF mutant mice.
AB  - Kindling is an animal model of epilepsy in which repeated electrical stimulations
      lead to progressive and permanent amplification of seizure activity, culminating
      in generalized convulsions. Each brief period of seizure activity during kindling
      epileptogenesis causes a marked, transient increase of the synthesis of brain
      derived neurotrophic factor (BDNF) in cortical and hippocampal neurons. We find
      that the development of kindling is markedly suppressed in mice heterozygous for
      a deletion of the BDNF gene. In contrast, the maintenance of kindling is
      unaffected. The mutant mice show lower levels of BDNF mRNA in cortical and
      hippocampal neurons after seizures than do wild-type mice. Hippocampal mossy
      fiber sprouting is augmented in BDNF mutants but there are no other morphological
      abnormalities. These results show that BDNF plays an important role in
      establishing hyperexcitability during epileptogenesis, probably by increasing
      efficacy in stimulated synapses.

PMID- 7649228
TI  - Fetal transplantation following spinal contusion injury results in chronic
      alterations in CNS glucose metabolism.
AB  - Glucose utilization of the injured rat spinal cord was determined using the
      autoradiographic technique of Sokoloff et al. (33). Animals were analyzed
      chronically (2 and 3 months) after spinal contusion injury alone or when a spinal
      lesion was followed by subchronic (10-day) intraparenchymal fetal spinal
      transplantation. At 2 and 3 months postinjury, spinal glucose utilization was
      reduced in dorsal gray and white matter above and below the lesion site. In
      addition, sensory regions of the forebrain and brain stem (e.g., nucleus gracilis
      and ventral posterior medial nucleus of the thalamus) had a lower basal metabolic
      rate than control animals. Decreased metabolic rates in supraspinal regions were
      reversed by the presence of a spinal graft at 3 but not at 2 months postinjury.
      Furthermore, gray matter in animals receiving an intraspinal transplant had
      elevated glucose utilization rates for several spinal segments rostral and caudal
      to the lesion epicenter. Graft glucose utilization was higher at 2 months (80-90
      mumol/100 g/min) than at 3 months (60-70 mumol/100 g/min) posttransplantation.
      These data are the first quantitative metabolic imaging of spinal and brain
      metabolism following spinal contusion injury and fetal transplantation. The study
      suggests that intraspinal transplants can become functionally integrated with
      adjacent host gray matter and can chronically alter specific postinjury metabolic
      patterns.

PMID- 7649229
TI  - Fiber and synaptic connections between embryonic retinal transplants and host
      retina.
AB  - The aim of this study was to investigate (a) whether embryonic retinal
      transplants can sprout fibers into a lesioned adult host retina and (b) if these
      fibers established synaptic connections with the host. Embryonic rat (E16-22) or
      human (9-13 weeks) retinal cells were transplanted to adult rats. Normal Long
      Evans rats received rat transplants. The hosts for human transplants were athymic
      nude rats. After varying survival times (3 to 11 months), animals were perfused
      with 4% paraformaldehyde (sometimes with added 0.1% glutaraldehyde). Glass
      microneedles, coated with DiI (a carbocyanine dye) were placed into the
      transplants which were then stored at room temperature in 2% paraformaldehyde for
      3-15 months. This filled the cells that had processes in the area where the
      needle had been placed. Gelatin-embedded eyecups were cut on a vibratome. DiI
      labeled transplant cells exhibited fiber outgrowth into the host retina. After
      photoconversion of the dye to an electron-dense precipitate, these neuronal
      processes could be followed with better resolution than with fluorescence.
      Occasionally, host cells could also be labeled by DiI placed into the graft,
      indicating fiber ingrowth of host fibers into the transplants. Selected
      photoconverted sections were embedded for electron microscopy. Synapses could be
      found along transplant processes that had grown into the host inner plexiform
      layer. These results indicate that neuronal fibers originating from embryonic
      retinal transplants form synapses in the host retina.

PMID- 7649230
TI  - Peripheral nerve pathology following sciatic cryoneurolysis: relationship to
      neuropathic behaviors in the rat.
AB  - Sciatic cryoneurolysis (SCN) is an experimental rat mononeuropathy model that
      produces neuropathic behavioral sequelae distinct from other neuropathy models.
      Following SCN, there is limited autotomy peaking in severity and incidence at 7
      14 days and delayed but sustained allodynia appearing at about 21 days, with no
      evidence of thermal hyperalgesia. This study quantified peripheral nerve
      pathology at weekly intervals following SCN to determine the relationship of
      nerve degeneration and regeneration to the resulting abnormal behaviors. Fiber
      histograms based on axon diameter and grid morphometry were used to quantify the
      pathologic state of nerve fibers, activated phagocytic cells, vessels, and edema
      at the lesion site. Approximately 90% of the axons demonstrated Wallerian-like
      degeneration by 3 days post-SCN. At 14 days, small diameter axons significantly
      increased in number from earlier times following SCN (P < 0.05) but were not
      significantly different from normal values. At 21 days, the number of small
      diameter axons was significantly increased over both 14 days (P < 0.05) and
      normal values (P < 0.05). At 28 days, intermediate diameter axons significantly
      increased in number with respect to all earlier time periods (P < 0.05). These
      increases in regenerating fibers overlapped with the development of peak autotomy
      at 7-14 days and the onset of allodynia after 21 days. Autotomy scores at 7 days
      positively correlated with grid morphometry data of regenerating axons (rho =
      0.7) and activated macrophages and Schwann cells (rho = 0.8) and inversely
      correlated with edema (rho = -0.8) using Spearman's rank correlation
      analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7649231
TI  - DNA end labeling (TUNEL) in Huntington's disease and other neuropathological
      conditions.
AB  - Deoxyribonucleic acid of cells undergoing apoptosis is cleaved by a calcium
      dependent endonuclease into oligonucleosomal-sized fragments. These fragments can
      be labeled using the enzyme terminal deoxynucleotidyl transferase so that the
      cells can be visualized immunohistochemically. Few investigators have evaluated
      this method in disease processes of the human central nervous system. The Tdt
      mediated dUTP-biotin nick end labeling (TUNEL) technique has been investigated in
      preliminary studies of a variety of pathologic conditions of the human brain
      (e.g., gliomas, traumatic brain injury, Parkinson's disease, Parkinson's
      Alzheimer's complex, multisystem atrophy, striatonigral degeneration). We focus,
      however, on Huntington's disease (HD) because of the availability of well
      characterized pathological stages for study, and also because of the
      neurodegenerative diseases studied to date, only Huntington's disease revealed
      significant and consistent labeling with this method. This implies a possibly
      unique nature to the mechanism of cell death in Huntington's disease compared to
      the other neurodegenerative diseases studied. TUNEL+ neurons were found in Grade
      1-4 HD neostriatum, while labeled astrocytes were found predominantly in the
      Grade 1 and 2 cases studied to date. TUNEL+ cells were also found in glioblastoma
      multiforme and traumatic brain injury. We conclude that while there appear to be
      several limitations associated with this technique, it may be useful for
      identifying both apoptosis and necrosis in certain neuropathological conditions.

PMID- 7649232
TI  - The first known use of vermillion.
AB  - Vermillion has been shown to be useful in preserving human bones from 5000 years
      ago. Remarkably well-preserved human bones have been found in the dolmenic burial
      'La Velilla' in Osorno (Palencia, Spain), carefully covered by pulverized
      cinnabar (vermillion) which ensured their preservation even in non-favorable
      climatic conditions. We believe the red powder was deliberately deposited for
      preservative use because no cinnabar mine is to be found within 160 km, because
      of the large amount (hundreds of kilograms) used, and because its composition,
      red mercuric sulphide, is similar to that of preparations used in technical
      embalming. This finding pushes back the data of the use of mercury ore for
      preservation by four millennia in South America, and by at least one millennium
      in the Old World. Chemical and thermal analyses of vermillion in La Velilla have
      demonstrated its great purity and shown that the cinnabar was pulverized and
      washed (but not heated), producing a bright red-orange tone.

PMID- 7649233
TI  - Blood flow rate in jejunal ischemia-reperfusion injury.
AB  - We examined changes in the blood flow rate in the course of jejunal ischemic
      injury using a laser Doppler flowmeter. For this purpose, we designed a sensor
      holding system, which involved the fixation of the sensor to the jejunum and
      allowed their movements to be synchronized. When the jejunum was reperfused after
      10 min of ischemia, the blood flow rate markedly increased and then gradually
      decreased to the initial level. A 30-min period of ischemia produced the slowest
      recovery of the blood flow rate. This system could be useful for monitoring the
      blood flow rate in different anatomical regions.

PMID- 7649234
TI  - Neural discharge can be modulated by carotid arterial injection of gastrin-17 in
      rat hypothalamic paraventricular nucleus.
AB  - Neural discharge in the hypothalamic paraventricular nucleus (PVN) was examined
      after gastrin-17 injection into the carotid artery in anesthetized rats. Neural
      discharge was increased by gastrin-17 injection into the carotid artery close to
      the cranium, and the response due to the gastrin was dose-dependent. No discharge
      response was seen when gastrin was injected into the jugular vein. These results
      suggest that gastrin circulating in the arterial blood can penetrate the blood
      brain barrier, and modulate neural PVN activity which is responsible for gastric
      acid secretion.

PMID- 7649235
TI  - Presence of hsp65 in bacterial extracts (OM-89): a possible mediator of orally
      induced tolerance?
AB  - Heat shock proteins (HSP) have been implicated in rodent models of autoimmunity,
      particularly arthritis, and there is suggestive though inconclusive evidence that
      they may also play a role in human autoimmune disease. The simplest hypothesis is
      based on molecular mimicry due to the amino-acid sequence homology between
      mammalian and microbial HSP. Recently OM-89, an extract of several strains of
      Escherichia coli, has shown some efficacy in the treatment of rheumatoid
      arthritis (RA) when taken orally. Using species-specific antibodies, we show here
      that OM-89 contains the 65 kDa HSP (hsp65), while hsp65 was not detected in
      another bacterial extract containing other microorganisms, including
      Staphylococcus aureus (OM-85). We suggest that if the human homologue of hsp65 is
      a relevant target antigen in the human disease, the efficacy of the preparation
      could be due to induction of oral tolerance or to switching the Th1 response
      towards Th2. Alternatively, even if the human hsp65 is not a target molecule in
      RA joints, OM-89 may evoke bystander suppression of joint inflammation via
      induction of TGF beta-secreting effector cells. These hypotheses should be tested
      in further studies.

PMID- 7649236
TI  - Growth hormone alters lymphocyte sub-populations and antibody production in dwarf
      rats in vivo.
AB  - Female dwarf rats at different ages were treated with recombinant porcine GH or
      with a potent sheep anti-rat GH serum. Body weight and spleen weight increased
      with GH and decreased with anti-GH treatment (p < 0.001). Neither GH nor anti-GH
      treatment resulted in a change in circulating WBCs, but GH decreased, while anti
      GH increased, RBC counts (p < 0.001). Similarly, GH treatment tended to decrease
      the ratio of CD4+:CD8+ T-cells while anti-GH increased (p < 0.05) the ratio. Anti
      GH treatment also enhanced the animals' ability to produce specific IgG in
      response to KLH injection. These results indicate that GH may have a
      physiological role in suppressing humoral immune function but may enhance cell
      mediated immunity.

PMID- 7649237
TI  - The influence of peripheral or central administration of ondansetron on stress
      induced gastric ulceration in rats.
AB  - Ondansetron (0.08, 0.15 or 0.3 mg/kg) injected s.c., every 12 h with the fourth
      dose given 0.5 h before experiments, dose-dependently lessened gastric glandular
      mucosal ulceration produced by cold-restraint stress for 2 h. When given
      intracerebrally (i.c.) (0.1, 0.5 or 1 microgram), using the same treatment
      regimen, infusion of ondansetron 1 microgram into the nucleus amygdaloideus
      centralis decreased stress-evoked ulcers; in contrast, injection of the same dose
      into the nucleus accumbens intensified these lesions. The associated stress
      induced stomach wall mast cell degranulation was unaffected by all s.c. or i.c.
      doses of ondansetron. Pretreatment with disodium cromoglycate i.p. alone, or
      concurrently with ondansetron s.c., prevented not only ulceration but also mast
      cell degranulation. 5-Hydroxytryptamine3 receptor antagonism appears to inhibit
      stress-evoked ulcers mainly by blocking the peripheral effects of the amine after
      its release from the gastric mucosal mast cells.

PMID- 7649238
TI  - Immunostimulating lipopeptide, LtriP (RP 56142): comparison of the effect on
      hepatic cytochrome P 450 modulation and radioprotection in male and female of
      three mouse strains.
AB  - The sex-dependent effect of lauroyl-L-Ala-D-gamma-Glu-L,L-A2pmNH2 (LtriP, RP
      56142) on hepatic microsomal cytochromes P 450 (cyt P 450) was studied in three
      mouse strains NMRI, C3H/OuJ and C3H/HeJ. In NMRI and C3H/OuJ, strains which are
      responsive to bacterial lipopolysaccharides (LPS-responsive), regardless of the
      sex of the mouse, significant decrease in the amount of cyt P 450 was observed
      after LtriP treatment, with a concomitant reduction in ethoxyresorufin-O
      deethylase (cyt P 450 1A-dependent) and 7-ethoxycoumarin-O-deethylase activities.
      This was not seen in C3H/HeJ (LPS-hyporesponsive) mice. These effects may be
      related to LtriP-dependent cytokine induction, since neither LtriP nor LPS
      stimulated interleukin-1 (IL-1) secretion by C3H/HeJ macrophages. 11- and 12
      hydroxylations (11- and 12-OH) of lauric acid were compared in C3H/OuJ and
      C3H/HeJ mice. LtriP depressed the total enzymatic conversion of lauric acid in
      the two strains without modification of the 11/12-OH ratio for C3H/OuJ or male
      C3H/HeJ mice. However, in females C3H/HeJ mice this decrease was particularly
      significant and concerned especially the 12-OH activity (a marker of cyt P450 4A
      family). Although males of the three strains were more sensitive to irradiation
      than females, LtriP exerted a sex-independent radioprotection on NMRI and C3H/OuJ
      mice. Its radioprotective effect was illustrated by the preservation of all the
      enzymatic activities studied in treated NMRI mice, contrary to irradiated control
      animals. In contrast, for the C3H/HeJ strain, males were not protected by LtriP
      treatment and, furthermore, females showed a marked sensitization to irradiation.
      The effects in CH3/HeJ strain implicate LtriP in the control of cyt P 450
      induction and of sensitivity to irradiation independently of IL-1 induction.

PMID- 7649239
TI  - Bicarbonate and chloride transport across rat ileal basolateral membrane.
AB  - The mechanisms of HCO3- and Cl- transport across basolateral membranes from rat
      ileum were investigated in isolated vesicles by means of uptake experiments.
      Neither Cl-/HCO3- exchanger nor Na(+)-(HCO3-)n cotransport seem to be present in
      ileal basolateral membranes. Moreover Cl- uptake is unaffected by cis Na+ and/or
      K+ gradients, indicating the absence of Na(+)-Cl-, K(+)-Cl- and Na(+)-K(+)-2Cl-
      symport activity. An electrically conductive pathway seems to be responsible for
      both HCO3- and Cl- fluxes. Evidence is also given for the presence of a Na+/H+
      exchanger at the basolateral pole of ileal enterocytes.

PMID- 7649240
TI  - Sr2+ can become incorporated into an agonist-sensitive, cytoplasmic Ca2+ store in
      a cell line derived from the equine sweat gland epithelium.
AB  - We have explored the properties of a Ca(2+)-dependent cell-signalling pathway
      that becomes active when cultured equine sweat gland cells are stimulated with
      ATP. The ATP-regulated, Ca(2+)-influx pathway allowed Sr2+ to enter the cytoplasm
      but permitted only a minimal influx of Ba2+. Experiments in which cells were
      repeatedly stimulated with ATP suggested that Sr2+, but not Ba2+, could become
      incorporated into the agonist-sensitive, cytoplasmic Ca2+ store. Further evidence
      for this was provided by experiments using ionomycin, a Ca2+ ionophore which has
      no affinity for Sr2+.

PMID- 7649241
TI  - Sperm precedence in a hermaphroditic nematode (Caenorhabditis elegans) is due to
      competitive superiority of male sperm.
AB  - When male and hermaphrodite Caenorhabditis elegans mate, the male's sperm
      outcompete the hermaphrodite's own sperm and fertilize a majority of the
      offspring. Here, we investigate the mechanism of male sperm precedence. We rule
      out the possibility that male sperm are stronger and more competitive because
      they are activated later than hermaphrodite sperm. We also find that a previously
      known gender difference in sperm activation does not influence sperm competition.
      Male sperm, rinsed free of seminal fluid, retained the capacity to take
      precedence after artificial insemination. Therefore, we conclude that male sperm
      themselves are competitively superior to hermaphrodite sperm. This trait
      maximizes outcrossing after mating and may increase both genetic diversity and
      heterozygosity of offspring whose parents, due to self-fertilization, may be
      highly homozygous.

PMID- 7649242
TI  - In vitro effects of methionine-enkephalin, somatostatin and insulin on cultured
      gonadal cells of the snail Helix aspersa.
AB  - Isolated snail gonadal cells were cultured in the presence of synthetic
      neuropeptides in order to determine the subsequent effect of these substances on
      gonadal synthetic activities. Gonadal cells were incubated for 24 h in
      concentrations of methionine-enkephalin, somatostatin and insulin ranging from
      10(-4) M to 10(-9) M, in medium 199 supplemented with 6% Ultroser G. Synthesis of
      DNA and protein by the cultured cells were simultaneously estimated by measuring
      incorporation of 3H thymidine and 35S methionine. The rate of labelled precursor
      incorporation was measured using the liquid scintillation technique. All
      substances tested exerted a dose-dependent effect. The synthetic activity of the
      cultured cells was highest when the concentration of the peptides added to the
      medium approximated the physiological levels. Methionine-enkephalin, somatostatin
      and insulin at 2 x 10(-8) M significantly increased 3H thymidine incorporation,
      by 62%, 69% and 69% respectively, and protein synthesis by 42%, 57% and 57%,
      respectively. In the case of juvenile gonadal cultured cells, a similar increase
      in 3H and 35S incorporation was registered for a 10(-7) M peptide concentration.
      Both lower and higher peptide concentrations inhibited 3H thymidine and 35S
      methionine incorporation. Pharmacological studies suggest the existence of
      methionine-enkephalin and somatostatin-like receptors on snail gonadal cells.
      These results indicate that our gonadal cell culture model provides a useful tool
      for the study of the neuroendocrinological control of the activity of snail
      gonadal cells.

PMID- 7649243
TI  - Baker's yeast, an attractant for baiting traps for Chagas' disease vectors.
AB  - We tested the attraction of volatile compounds, produced by the aerobic growth of
      Saccharomyces cerevisiae on saccharose for Triatoma infestans. For these tests,
      we exploited the behavioural characteristic of these haematophagous insects of
      dropping when searching for food. In olfactometer assays, yeast cultures
      activated and attracted bugs as effectively as a mouse. The attraction of the
      cultures was significantly reduced when the carbon dioxide released was partially
      eliminated using potassium hydroxide. Yeast cultures were also tested as lures in
      a novel trap device. A baited device for trapping Chagas' disease vectors using
      the behavioural peculiarities of T. infestans and this simple attractant is
      described.

PMID- 7649244
TI  - Nitric oxide and oxygen radicals: a question of balance.
AB  - The production of superoxide and nitric oxide individually has been associated
      with the development of several diseases but only recently has it been realised
      that interactions between them may also be important in disease pathology. The
      central hypothesis which is emerging is that the balance between nitric oxide and
      superoxide generation is a critical determinant in the aetiology of many human
      diseases including atherosclerosis, neurodegenerative disease, ischaemia
      reperfusion and cancer. These ideas are discussed in this short overview and
      placed in the context of the current and future status of therapies which could
      modulate the balance between nitric oxide and superoxide.

PMID- 7649245
TI  - Nitric oxide regulates mitochondrial respiration and cell functions by inhibiting
      cytochrome oxidase.
AB  - Nitric oxide (NO) reversibly inhibits mitochondrial respiration by competing with
      oxygen at cytochrome oxidase. Concentrations of NO measured in a range of
      biological systems are similar to those shown to inhibit cytochrome oxidase and
      mitochondrial respiration. Inhibition of NO synthesis results in a stimulation of
      respiration in a number of systems. It is proposed that NO exerts some of its
      main physiological and pathological effects on cell functions by inhibiting
      cytochrome oxidase. Further NO may be a physiological regulator of the affinity
      of mitochondrial respiration for oxygen, enabling mitochondria to act as sensors
      of oxygen over the physiological range.

PMID- 7649246
TI  - On the physical basis for the cis-positive rule describing protein orientation in
      biological membranes.
AB  - The topology of hydrophobic intramembrane proteins is characterized by a
      statistical asymmetry in the distribution of positively-charged residues on the
      two sides of the membrane, the 'inside- or cis-positive rule'. A mechanism is
      proposed involving only neutral residue transfer. For a tightly bound polypeptide
      adsorbed on the membrane and not at equilibrium, the pK values of the ionic
      residues related to dissociation of the proton into the aqueous phase bulk are
      increased because of interaction with the negative charges at the membrane
      surface. The pK shift would selectively neutralize aspartate and glutamate
      residues, favoring their translocation across the membrane, while stabilizing the
      impermeant positively charged state of lysine and arginine residues.

PMID- 7649247
TI  - The effect on actin ATPase of phalloidin and tetramethylrhodamine phalloidin.
AB  - Actin polymerization has been studied in the absence of excess nucleotide. Using
      G-actin ATP monomers, it was shown that mechanical shearing stimulates ATP
      hydrolysis. The procedures used enabled the detection of differential effects of
      phalloidin and tetramethylrhodamine-phalloidin, on the P(i)-release step of the
      actin ATPase. It is concluded that tetramethylrhodamine, in contrast to
      phalloidin, accelerates P(i)-release from actin filaments.

PMID- 7649248
TI  - Identification and localization of the first glutaredoxin in leaves of a higher
      plant.
AB  - Glutaredoxin(thioltransferase) has been identified and purified to homogeneity
      from spinach leaves. Its cytosolic localization was demonstrated by
      chromatographic and immunological analysis of extracts from isolated spinach
      chloroplasts and mitochondria, respectively. Spinach glutaredoxin shows a
      significant crossreactivity with antibodies raised against E. coli glutaredoxin
      and possesses a specific thioltransferase activity comparable to that of the E.
      coli protein. Minor thioltransferase activities (less than 10% of total leaf
      activity) have been observed in spinach chloroplasts which are probably due to
      the presence of trypsin inhibitor and thioredoxins (TRf and TRm).

PMID- 7649249
TI  - Repression of transcriptional activity by heterologous KRAB domains present in
      zinc finger proteins.
AB  - We report the characterization of three novel members of the KRAB-domain
      containing C2-H2 zinc finger family (ZNF133, 136 and 140). KRAB (Kruppel
      associated box) is an evolutionarily conserved protein domain found N-terminally
      with respect to the zinc finger repeats that encodes the DNA binding domain.
      ZNF133 and ZNF140 have both the KRAB A- and KRAB B-boxes present at their N
      terminus, whereas ZNF136 contains only the KRAB A-box. We have previously
      demonstrated that the KRAB domains derived from ZNF133 and ZNF140 are potent
      transcriptional repression domains [Margolin et al. (1994) Proc. Natl. Acad. Sci.
      USA 91, 4509-4513]. The KRAB domain from ZNF136, containing only subdomain A, is
      a considerable weaker suppression domain; however, when fused to the heterologous
      KRAB B subdomain of ZNF10 (KOX1) the two subdomains from a KRAB domain which
      induces repression as potently as previously reported KRAB domains.

PMID- 7649250
TI  - In vivo assembly of plasmid-expressed ribosomal protein S7 of Thermus
      thermophilus into Escherichia coli ribosomes and conditions of its
      overexpression.
AB  - Researchers still have great difficulty in isolating individual ribosomal
      proteins from the ribosome in quantities high enough for structural research. To
      this end, when studying protein S7, we created an E. coli overproducer of the
      recombinant protein S7 of Thermus thermophilus. The vector for expression was pQE
      32 having a strong promoter of E. coli phage T5 and six triplets of His at the 5'
      end. This N-terminal six His tag of the fusion protein is responsible for binding
      to Ni-NTA-resin and allows purifying the protein in one step. The yield of the
      recombinant protein was 20% and more of the total cellular proteins. In addition
      we have shown that the recombinant thermophilic protein is incorporated in vivo
      into the ribosome of E. coli despite the fact that these proteins (thermophilic
      and mesophilic) have a rather low homology, only 52%. This fact provides a base
      for the system to study functions of individual proteins.

PMID- 7649251
TI  - Influence of synthetic peptides, corresponding to fragments of the human alpha-2
      interferon molecule, on the proliferation of lymphoblastoid cells in vitro.
      Growth inhibition and receptor binding.
AB  - Influence of nine synthetic peptides from the C-terminal part of human alpha-2
      interferon (IFN) molecule on growth of a human T-lymphoblastoid cell line MT-4
      was investigated. It was shown that some peptides inhibited the proliferation of
      MT-4 cells. It was also found that MT-4 cells expressed specific receptors on the
      outer surface of the plasma membrane. All studied peptides competed for binding
      to a common binding site. Antiproliferative activity of the peptides correlated
      with their length and affinity to receptors on the outer membrane of MT-4 cells.

PMID- 7649252
TI  - The membrane proximal region of the cytoplasmic domain of the growth hormone
      receptor is involved in the activation of Stat 3.
AB  - Growth hormone receptor (GHR) signaling involves activation of the Janus Kinases
      (Jak) and of Stat proteins (signal transducers and activators of transcription).
      Growth hormone (GH) induces transcriptional activation of c-fos gene and the c
      sis inducible element (SIE) of its promoter was shown to bind the Stat proteins.
      Using cells co-transfected with GHR and Stat 3 expression vectors, we directly
      demonstrate that GH induces tyrosine phosphorylation of Stat 3 and its binding to
      the SIE probe. We showed, using mutant forms of GHR, that only the cytoplasmic
      membrane proximal domain of the receptor, including a conserved proline rich
      region (box 1), is required for this effect.

PMID- 7649253
TI  - The Na(+)-translocating NADH:ubiquinone oxidoreductase from the marine bacterium
      Vibrio alginolyticus contains FAD but not FMN.
AB  - The Na(+)-translocating NADH:ubiquinone oxidoreductase from Vibrio alginolyticus
      was extracted from the bacterial membranes and purified by ion exchange
      chromatographic procedures. The enzyme catalyzed NADH oxidation by suitable
      electron acceptors, e.g. menadione, and the Na+ and NADH-dependent reduction of
      ubiquinone-1. Four dominant bands and a number of minor bands were visible on SDS
      PAGE that could be part of the enzyme complex. Flavin analyses indicated the
      presence of FAD but no FMN in the purified enzyme. FAD but no FMN were also
      present in V. alginolyticus membranes. FAD is therefore a prosthetic group of the
      Na(+)-translocating NADH:ubiquinone oxidoreductase and FMN is not present in the
      enzyme. The FAD was copurified with the NADH dehydrogenase. The purified enzyme
      exhibited an absorption spectrum with a maximum at 450 nm that is typical for a
      flavoprotein. Upon incubation with NADH this absorption disappeared indicating
      reduction of the enzyme-bound FAD.

PMID- 7649254
TI  - gamma-Glutamyltransferase expression during all-trans retinoic acid-induced
      differentiation of hematopoietic cell lines.
AB  - gamma-Glutamyltransferase activity, genes transcripts and differentiation by all
      trans retinoic acid have been investigated in cultured HL-60, U937, and K562
      cells. Acquisition of morphological and functional characteristics confirmed the
      terminal differentiation of HL-60 and U937 cells. All-trans retinoic acid
      increased gamma-glutamyltransferase activity in a cell type- and time dependent
      manner. Treatments with all-trans retinoic acid isomers and structurally analogs
      showed that only retinoids with carboxylic acid group were able to induce enzyme
      activity in terminal differentiated cells. Additionally, the analysis of gamma
      glutamyltransferase genes transcription products demonstrated clearly that, both
      in untreated and in RA treated cells, only mRNA type I transcribed from the gene
      6, was expressed.

PMID- 7649255
TI  - Leucine-58 in the putative 5th helical region of human interleukin (IL)-6 is
      important for activation of the IL-6 signal transducer, gp130.
AB  - A model of the tertiary structure of human IL-6, derived from the crystal
      structure of granulocyte-colony stimulating factor, reveals a 5th helical region
      in the loop between the first and second alpha-helix. To investigate the
      importance of this region for biological activity of IL-6, residues Glu-52, Ser
      53, Ser-54, Lys-55, Glu-56, Leu-58, and Glu-60 were individually replaced by
      alanine. IL-6.Leu-58Ala displayed a 5-fold reduced biological activity on the IL
      6 responsive human cell lines XG-1 and A375. This reduction in bioactivity was
      shown to be due to a decreased capacity of the mutant protein to trigger IL-6
      receptor-alpha-chain-dependent binding to the IL-6 signal transducer, gp130.

PMID- 7649256
TI  - Antisense mapping the MOR-1 opioid receptor: evidence for alternative splicing
      and a novel morphine-6 beta-glucuronide receptor.
AB  - Although MOR-1 encodes a mu opioid receptor, its relationship to the
      pharmacologically defined mu receptor subtypes has been unclear. Antisense
      mapping now suggests that these subtypes result from alternative splicing of MOR
      1. Three oligodeoxynucleotide probes targeting exon 1 and another
      oligodeoxynucleotide directed against the coding region of exon 4 block
      supraspinal morphine analgesia, a mu1 action, while five of six
      oligodeoxynucleotides directed against exons 2 and 3 are inactive. Inhibition of
      gastrointestinal transit and spinal morphine analgesia, two mu2 actions, are
      blocked only by the probe against exon 4 and not by those directed against exon
      1. In contrast, the analgesic actions of the extraordinarily potent mu drug
      morphine-6 beta-glucuronide are blocked by six different antisense
      oligodeoxynucleotides targeting exons 2 and 3, but not by those acting on exons 1
      or 4. These results suggest that the mu1 and mu2 receptor subtypes originally
      defined in binding and pharmacological studies result from alternative splicing
      of MOR-1 while morphine-6 beta-glucuronide acts through a novel, previously
      unidentified receptor which is yet another MOR-1 splice variant.

PMID- 7649257
TI  - Purification and structural characterization of the CD11b/CD18 integrin alpha
      subunit I domain reveals a folded conformation in solution.
AB  - The alpha subunits of the leukocyte CD11/CD18 integrins contain an approximately
      200 amino acid 'inserted' or I domain. The I domain of the cell-surface Mac-1
      (CD11b/CD18) integrin has been shown to be the major recognition site for several
      adhesion ligands, including iC3b, fibrinogen, factor X, and ICAM-1. The I domain
      from the Mac-1 alpha subunit has been expressed in Escherichia coli as a soluble
      GST-fusion protein containing a factor Xa sensitive cleavage site. Analytical
      characterization of the purified I domain reveals that it is obtained in very
      high quality at high yields. CD and NMR spectra indicate that I domain adopts a
      predominantly folded structure in solution, independent of the remainder of the
      alpha subunit. Addition of Ca2+ and Mg2+ did not significantly perturb the
      structural conformation.

PMID- 7649258
TI  - Evidence for, and characterization of, a lipopolysaccharide-inducible adenosine
      A2 receptor in human tracheal gland serous cells.
AB  - Human tracheal glands are considered as the principle secretory structures in the
      bronchotracheal tree. In earlier studies, we successfully performed primary
      cultures of human tracheal gland (HTG) serous cells and noted that these cells
      were responsive to many secretagogues including purinergic agonists but not to
      the inflammatory mediator adenosine. In this study, we demonstrate that adenosine
      was capable of including stimulation of protein secretion by HTG serous cells
      which had previously been cultured in pro-inflammatory conditions (induced by
      lipopolysaccharide (LPS)). This stimulation was inhibited by 8
      phenyltheophyllline but not by dipyridamole, which is indicative of a P1
      purinoceptor. This inducible receptor is the adenosine A2 subtype [rank potency
      order: (5'-(N-ethyl)-carboxamidoadenosine (NECA) > adenosine > N6
      (phenylisopropyl)-adenosine (PIA); and stimulation of adenylyl cyclase]. The
      adenosine-induced protein secretion was concentration-dependent, however,
      increased intracellular cyclic adenosine monophosphate (cAMP) was not dependent
      on the concentration of adenosine. The adenosine-induced secretion and the ATP
      induced secretion were shown to be additive. This study concludes that there is
      evidence of a LPS-inducible adenosine A2 receptor in human tracheal gland serous
      cells.

PMID- 7649259
TI  - Biosynthesis and apical localization of the urokinase receptor in polarized MDCK
      epithelial cells.
AB  - The biosynthesis and the surface localization of the urokinase plasminogen
      activator receptor (uPAR) were analysed in MDCK epithelial cells and in
      unpolarized fibroblasts. No differences were observed with respect to rate of
      synthesis, nature of precursors and time of surface appearance. uPAR was
      localized particularly at the focal and cell-cell contacts when expressed in
      fibroblasts. On the contrary, in MDCK cells uPAR was found mostly on the apical
      surface; in agreement with its localization, down-regulation of uPAR by the uPA
      PAI-1 complex was observed only from the apical membrane.

PMID- 7649260
TI  - Isolation and characterization of a yeast gene, MPD1, the overexpression of which
      suppresses inviability caused by protein disulfide isomerase depletion.
AB  - MPD1, a yeast gene the overexpression of which suppresses the inviability caused
      by the loss of protein disulfide isomerase (PDI) was isolated and characterized.
      The MPD1 gene product retained a single disulfide isomerase active site sequence
      (APWCGHCK), an N-terminal putative signal sequence, and a C-terminal endoplasmic
      reticulum (ER) retention signal, and was a novel member of the PDI family. The
      gene product, identified in yeast extract, contained core size carbohydrates.
      MPD1 was not essential for growth, but overexpression of the gene suppressed the
      maturation defect of carboxypeptidase Y caused by PDI1 deletion, indicative of
      the related function to PDI in the yeast ER.

PMID- 7649261
TI  - A distal Sp1-element is necessary for maximal activity of the human gastrin gene
      promoter.
AB  - Studies of transgenic mice have shown that transcriptional control of the gastrin
      gene exhibits significant species differences. Transfection of the human gastrin
      promoter in murine cells have depicted proximal Sp1, E-box and CACC elements as
      the major determinants of transcription. We have examined cis-regulatory elements
      of the human promoter on a human gastrin expressing cell line and find that a
      distal -135 to -142 Sp1 element is necessary for maximal activity. Alignment of
      the mouse and human promoters shows that the proximal human Sp1 and CACC elements
      are not conserved, whereas the E-box element is retained. The distal Sp1 element
      is present in mouse but exhibits a C to T transition in the core that is likely
      to reduce binding affinity of Sp1. We conclude that gastrin gene transcription is
      regulated by distinct elements in man and rodents.

PMID- 7649263
TI  - Cloning and characterization of a cDNA encoding a cellobiose dehydrogenase from
      the white rot fungus Phanerochaete chrysosporium.
AB  - The cDNA of cellobiose dehydrogenase (CDH) from Phanerochaete chrysosporium has
      been cloned and sequenced. The 5' end was obtained by PCR amplification. The cDNA
      contains 2310 translated bases excluding the poly(A) tail. The deduced mature
      protein contains 770 amino acid residues and is preceded by a 18 residue long
      signal peptide. The regions of the amino acid sequence corresponding to the heme
      and FAD domains of CDH were identified as well as the nucleotide-binding motif,
      the disulfide pairing and a methionine residue chelating the heme iron. No
      homologous sequences were found for the heme domain, however, the FAD domain
      appears to be distantly related to the GMC oxidoreductase family.

PMID- 7649262
TI  - Ribosomal protein L22 from Thermus thermophilus: sequencing, overexpression and
      crystallisation.
AB  - The gene for the ribosomal protein L22 from Thermus thermophilus has been
      sequenced and overexpressed in Escherichia coli. A multiple sequence alignment
      was carried out for all proteins of the L22 family reported so far. The
      recombinant protein was purified and crystallized. The crystals belong to the
      space group P2(1)2(1)2(1), with cell parameters of a = 32.6 A, b = 66.0 A, c =
      67.8 A.

PMID- 7649264
TI  - Selective disulphide linkage of plant thionins with other proteins.
AB  - Thionins are shown to form disulphide linkages with other proteins. The reaction
      with bacterial enzymes beta-glucuronidase and neomycin phosphotransferase II
      could be prevented and reversed with dithiothreitol and blocked with N
      ethylmaleimide. Other cysteine-rich low-molecular-weight toxic peptides from
      plants (LTP-3 from barley and P19 from potato) did not react as the thionins.
      Certain cysteine-containing proteins, such bovine serum albumin, ovalbumin and
      cytochrome c, reacted with thionins, while others, including carbonic anhydrase,
      soybean trypsin inhibitor, bovine-lung trypsin inhibitor and phosphorylase B did
      not. Selectivity of the reaction with a periplasmic component of the
      phytopathogenic bacterium Pseudomonas solanacearum was also shown.

PMID- 7649266
TI  - Coordination of a histidine residue of the protein-component S to the cobalt atom
      in coenzyme B12-dependent glutamate mutase from Clostridium cochlearium.
AB  - Electron paramagnetic resonance (EPR) spectroscopy of glutamate mutase from
      Clostridium cochlearium was performed in order to test the idea, that a histidine
      residue of component S replaces the dimethylbenzimidazole ligand of the Co-atom
      during binding of coenzyme B12 to the enzyme. The shapes and the superhyperfine
      splitting of the gz-lines of the Co(II) EPR spectra were used as indicators of
      the interaction of the axial base nitrogen with the Co-atom. A mixture of
      completely 15N-labelled component S, unlabelled component E, coenzyme B12 and
      glutamate gave slightly sharper gz-lines than that with unlabelled component S. A
      more dramatic change was observed in the Co(II) spectrum of the inactivated
      enzyme containing tightly bound cob(II)alamin, in which unlabelled component S
      caused a threefold superhyperfine-splitting of the gz-line, whereas the 15N
      labelled protein only caused a twofold splitting, as expected for a direct
      interaction of a nitrogen of the enzyme with the Co-atom. By using a sample of
      15N-labelled component S, in which only the histidines were 14N-labelled, the EPR
      spectra showed no difference to those with unlabelled component S. The
      experiments indeed demonstrate a replacement of the dimethylbenzimidazole ligand
      in coenzyme B12 by a histidine when bound to glutamate mutase. The most likely
      candidate is H16, which is conserved among the carbon skeleton rearranging
      mutases and methionine synthase.

PMID- 7649265
TI  - Molecular mimicry and ankylosing spondylitis: possible role of a novel sequence
      in pullulanase of Klebsiella pneumoniae.
AB  - Molecular mimicry has been shown between two sequences of Klebsiella pneumoniae
      pulD secretion protein (DRDE) with HLA-B27 (DRED) and pulA (pullulanase) enzyme
      (Gly-X-Pro) with types I, III and IV collagen respectively. IgG antibody levels
      in AS patients were elevated against 16mer synthetic peptides of HLA-B27 and pulD
      by enzyme immunosorbent assay (ELISA) compared to controls (P < 0.001). ELISA
      assays against K. pneumoniae grown in the absence and presence of pullulan
      demonstrated significant levels of IgA antibody in AS patients compared to
      controls (P < 0.001). Increased IgA and IgG antibody levels to pulA and types I
      and IV collagen were observed in AS patients compared to controls (P < 0.001).
      These observations could be relevant in the sequence of molecular events in AS.

PMID- 7649267
TI  - Cleavage points of rabbit skeletal myosin light chains selectively modified in
      situ by limited proteolysis: structural characteristics of the neoformed
      isozymes.
AB  - The functional significance of myosin light chains in vertebrate striated muscle
      is an issue of interest any myosin species selectivity modified by papain or
      trypsin in their LC1 and LC2 light chains are potentially useful for further
      investigation. We therefore determined the cleavage sites resulting in the (T)
      LC1', (P)-LC1' and (T)-LC2'species. Sequence analysis of (T)-LC1' indicated that
      the cleavage point in LC1 is at Lys7. Under appropriate conditions papain rapidly
      cleaves a short N-terminal segment from myosin light chain 1 and produces a new
      isozyme specifically modified in its essential light chain 1. The cleavage
      occurred at either Ala11, Ala12, or Ala13, the Ala11 cleavage being the most
      frequent. Trypsin was used to produce a myosin species with a regulatory light
      chain 2 specifically truncated of a short N-terminal segment. The cleavage was
      specific at Arg8 with no indication of other significant cleavage sites in this
      LC2. The effects of trypsin and papain on myosin light chains are different,
      indicating different proteolytic specificities. None of these modifications,
      including (CT)-LC2" cleavage at Phe19, changed the K(+)-EDTA- and Ca(2+)-ATPase
      activities of monomeric myosin significantly, indicating that LC1 and LC2 N
      terminal have little or no direct influence on the active site. An electric
      birefringence study also showed that these modified species retained their
      average shape and flexibility. These observations are essential in showing that
      the role of light chain extremities is expressed only in the presence of a
      minimum of structural organization (filament or acto-myosin complex).

PMID- 7649268
TI  - The control of sialyltransferase activity in tumor-cell lines derived from
      different tissues in multifactorial.
AB  - The activities of the sialyltransferase enzymes and the resulting expression of
      sialoglycoproteins were examined in tumor cells derived from different tissues in
      order to gain a greater understanding of the factors controlling the cell
      glycosylation state. Cell-cell contact, which is dependent on cell confluency
      state, was shown to influence glycosylation in the neurally-derived mouse neuro
      2A neuroblastoma and the C6 glioma cell lines. Both showed a relatively high
      level of cell sialyltransferase activity under sub-confluent conditions with
      activity decreasing upon the formation of cell-cell contacts associated with
      confluency. A parallel decrease in the expression of sialoglycoproteins, as
      determined by lectin blot analysis, was observed under these conditions. In
      contrast, the H411e hepatoma cell line showed an increase in enzyme activity with
      confluency with the susceptibility of the enzyme in this cell line to
      glucocorticoid induction only being detected in sub-confluent cell cultures. The
      number of trypsinisation cycles of the cells was also shown to affect the enzyme
      activity of the neuro-2A and C6 cells with an increase in enzyme activity
      coincident with passage number being observed in the neuro-2A cells, and a
      decrease in the C6 glioma cell line. Trypsinisation had no effect on enzyme
      activity in the H411e cells. These results demonstrate that the control of
      sialyltransferase activity in tumor cells is multifactorial with the tissue of
      origin playing a key role.

PMID- 7649269
TI  - Effects of the selective protein kinase C inhibitor Ro 31-7549 on human
      angiotensin II receptor desensitisation and intracellular calcium release.
AB  - The mechanism underlying type I angiotensin II (Ang II) receptor (AT1 receptor)
      desensitisation is unknown. Structural features suggest it may be a substrate for
      protein kinase C (PKC). The effects of a selective PKC inhibitor, Ro 31-7549, on
      receptor desensitisation were investigated in CHO cells expressing the human AT1
      receptor. Desensitisation was demonstrated with respect to the calcium response
      to Ang II in Fura-2-loaded cells. Ro 31-7549 had no effect on desensitisation.
      However, pretreatment with Ro 31-7549 caused a dose-dependent reduction in
      calcium release from intracellular stores. PKC may therefore act at a locus
      distal from the receptor itself.

PMID- 7649270
TI  - Visualization of protein transport along the secretory pathway using green
      fluorescent protein.
AB  - We have expressed green fluorescent protein (GFP) from A. victoria in the
      secretory pathway of HeLa cells by fusing it to the C-terminus of a secretory
      protein, chromogranin B. Under normal culture conditions at 37 degrees C
      maturation of GFP to the fluorescent form was not detectable. However,
      fluorescent GFP was observed when biosynthetic protein transport was arrested at
      the intermediate compartment or the trans-Golgi network by temperature blocks (15
      degrees C and 20 degrees C, respectively). Reversal of the temperature blocks
      allowed the visualization of secretion of fluorescent GFP and offers the
      possibility to analyse transport in the secretory pathway in living cells.

PMID- 7649271
TI  - Identification of kappa- and delta-opioid receptor transcripts in immune cells.
AB  - To investigate the role of opioids as direct modulators of the immune response,
      we have searched for expression of the recently cloned delta, mu and kappa opioid
      receptors in immune cells. We have devised a reverse transcriptase-polymerase
      chain reaction strategy which specifically detects a region spanning putative
      transmembrane regions 2 to 7 for each transcript in both human and mouse immune
      cells. In human peripheral blood lymphocyte and monocyte preparations, delta was
      undetectable while the kappa transcript was present. The analysis of human cell
      lines revealed low but significant levels of delta opioid receptor transcripts in
      T, B or monocyte cell lines while the kappa transcript was found in B cell lines
      only. Investigation of murine cells showed the presence of transcript for the
      delta receptor in splenocytes and in some T and B cell lines. Unexpectedly, no
      expression of the mu receptor was detected. Sequence analysis of PCR products
      demonstrated nucleotide identity between immune and neuronal transcripts,
      indicating that they derive from the same genes. In conclusion, our results lead
      to the identification of kappa and delta opioid receptor transcripts in immune
      cells.

PMID- 7649272
TI  - Interaction of DNA binding domain of HNF-3 alpha with its transferrin enhancer
      DNA specific target site.
AB  - Transferrin hepato-specific gene enhancer, associated with the liver-enriched HNF
      3 alpha transcriptional factor and ubiquitous proteins, is a complex molecular
      edifice maintained through DNA-protein and protein-protein interactions. As a
      first step to understand the mechanisms responsible for its organization and
      activity, we have analyzed the interaction of the DNA binding domain of HNF-3
      alpha (HDBD) with a specific DNA segment present in the transferrin enhancer by
      different biophysical techniques. The kinetic constants of this interaction were
      measured using surface plasmon resonance. The HDBD-DNA interaction was also
      characterized by circular dichroism and fluorescence spectroscopy. HDBD binds to
      its specific DNA site with high affinity (Kd approximately equal to 10(-8) M).
      The affinity is reduced after sequence modification of the target DNA. Size
      exclusion chromatography and binding stoichiometry determined by fluorescence
      measurements indicate that the protein is present in a monomeric form before and
      after interaction with the DNA. The secondary structure of the protein was not
      significantly altered upon binding to specific DNA. By contrast, a structural
      change of DNA by interaction with HDBD seems to occur.

PMID- 7649273
TI  - The role of ATP hydrolysis in the function of the chaperonin GroEL: dynamic
      complex formation with GroES.
AB  - In order to understand the role of ATP hydrolysis of the chaperonin GroEL during
      protein folding, we have studied GroEL-GroES complex formation in the presence of
      ATP or ADP by using capillary electrophoresis and surface plasmon resonance.
      Capillary electrophoresis analysis showed that the GroEL 14-mer and GroES 7-mer
      formed a 1:1 complex in the presence of ATP. In the presence of ADP, both the
      association and dissociation rates of the complex were slower by about one order
      of magnitude than the rates in the presence of ATP at 25 degrees C. The
      implications of such a stable complex on the overall mechanism of chaperonin
      function are discussed.

PMID- 7649274
TI  - Cooperative interactions in the tandem of oligonucleotide derivatives arranged at
      complementary target. Quantitative estimates and contribution of the target
      secondary structure.
AB  - The intraduplex reaction of the alkylating reagent CIRCH2NHpd(TTCCCA) (X, ClR is
      p-(N-2-chloroethyl-N-methylaminophenyl) residue) with the target 26-mer
      d(TTGCCTTGAATGGGAAGAGGGTCATT) (P) in the presence of effectors was studied. The
      effectors used were Phn-L-pd(TTCAAGGC)p-L-Phn (E1) and Phn-L-pd(TGACCCTC)p-L-Phy
      (E2), where Phn is N-(2-hydroxyethyl)-phenazinium residue and L is NHCH2CH2NH
      spacer. The dependence of the alkylation extent of the target on the reagent
      concentration was treated using the equation derived earlier for the two
      component system (reagent + target) to calculate association constants of X with
      P, PE1, PE2 and PE1E2. The latter were found to be Kxe1 = 6.75 x 10(5) M-1, Kxe2
      = 4.15 x 10(4) M-1 and Kxe12 = 5.87 x 10(6) M-1 as compared with the affinity of
      X to P Kx = 2.16 x 10(4) M-1 in the absence of effectors. Taking into account the
      internal structure of the target, co-operativity parameters describing
      interactions in the tandem E1 x X x E2 arranged at the target were calculated as
      alpha 1 = 16, alpha 2 = 10 and alpha 12 = 139 for the duplexes PXE1, PXE2 and
      PXE1E2.

PMID- 7649275
TI  - Differential expression of voltage-activated Na+ currents in two prostatic tumour
      cell lines: contribution to invasiveness in vitro.
AB  - The voltage-gated ionic currents of two rodent prostatic cancer cell lines were
      investigated using the whole-cell patch clamp technique. The highly metastatic
      Mat-Ly-Lu cells expressed a transient, inward Na+ current (blocked by 600 nM
      tetrodotoxin), which was not found in any of the weakly metastatic AT-2 cells.
      Although both cell lines expressed a sustained, outward K+ current, this occurred
      at a significantly higher density in the AT-2 than in the Mat-Ly-Lu cells.
      Incubation of the Mat-Ly-Lu cell line with 600 nM tetrodotoxin significantly
      reduced the invasive capacity of the cells in vitro. Under identical conditions,
      tetrodotoxin had no effect on the invasiveness of the AT-2 cells.

PMID- 7649276
TI  - The linoleic acid metabolite 13-HODE modulates degranulation of human
      polymorphonuclear leukocytes.
AB  - The effect of the linoleic acid metabolite 13-hydroxyoctadecadienoic acid human
      polymorphonuclear leukocytes (PMNs) was investigated by measuring the expression
      of CD11b and CD67 on the plasma membrane. 13-HODE (5 microM) by itself induced
      degranulation of PMNs, but to a lesser extent as compared to PAF and fMLP. In
      addition, 13-HODE was found to inhibit the PAF-induced degranulation whereas an
      additive effect on the fMLP-induced PMNs degranulation was observed. These
      results indicate that 13-HODE can play a modulatory role in degranulation of
      PMNs.

PMID- 7649277
TI  - 1H NMR spectroscopy reveals that mouse Hsp25 has a flexible C-terminal extension
      of 18 amino acids.
AB  - The small heat-shock proteins (Hsps) exist as large aggregates and function by
      interacting and stabilising non-native proteins in a chaperone-like manner. Two
      dimensional 1H NMR spectroscopy of mouse Hsp25 reveals that the last 18 amino
      acids have great flexibility with motion that is essentially independent of the
      domain core of the protein. The lens protein, alpha-crystallin, is homologous to
      Hsp25 and its two subunits also have flexible C-terminal extensions. The flexible
      region in Hsp25 encompasses exactly that expected from sequence comparison with
      alpha-crystallin implying that both proteins have similar structures and that the
      C-terminal extensions could be of functional importance for both proteins.

PMID- 7649278
TI  - Effects of vasoactive substances and cAMP related compounds on adrenomedullin
      production in cultured vascular smooth muscle cells.
AB  - To elucidate the regulation mechanism of adrenomedullin (AM) production in blood
      vessels, we examined the effects of 30 substances on AM production in cultured
      rat vascular smooth muscle cells (VSMCs). Forskolin and 8-bromo-cAMP suppressed
      production and gene transcription of AM. Since VSMC expresses AM receptors
      coupled with adenylate cyclase, AM production may be regulated by intracellular
      cAMP concentration. Thrombin, vasoactive intestinal polypeptide and interferon
      gamma also inhibited AM production, while angiotensin II, endothelin-1,
      bradykinin, substance P, adrenaline, phorbol ester and fetal calf serum
      stimulated AM production in VSMC. These results suggest that AM production is
      regulated by a variety of substances, indicating complex systems regulating AM
      production.

PMID- 7649280
TI  - Temperature-induced exposure of hydrophobic surfaces and its effect on the
      chaperone activity of alpha-crystallin.
AB  - alpha-Crystallin, the major protein of the ocular lens, is known to have
      extensive similarities to small heat shock proteins and to act as a molecular
      chaperone. The exposure of hydrophobic surfaces on alpha-crystallin was studied
      by fluorescence spectroscopy using the hydrophobic probe bis-ANS. Upon heating
      the protein undergoes a conformational transition which is associated with a
      marked increase in surface hydrophobicity. This transition, which occurs between
      approximately 38 and 50 degrees C, lacks reversibility. The increase in surface
      hydrophobicity correlates with the increased chaperone activity of the protein.
      These results indicate that hydrophobic interactions play a major role in the
      chaperone action of alpha-crystallin.

PMID- 7649279
TI  - Dissociation between exocytosis and Ca(2+)-channel activity in mouse pancreatic
      beta-cells stimulated with calmidazolium (compound R24571).
AB  - Calmidazolium, a calmodulin inhibitor, suppressed influx of Ca2+ through voltage
      gated Ca2+ channels in mouse pancreatic beta-cells. Despite this fact,
      calmidazolium stimulated insulin release from beta-cells at basal glucose
      concentration. This effect was not mediated by protein kinase C (PKC), since it
      persisted in PKC-depleted cells. RpcAMPS significantly attenuated the
      calmidazolium-stimulated insulin secretion, indicating that calmidazolium acts,
      at least partly, through PKA. The compound also stimulated insulin secretion from
      electropermeabilized beta-cells, indicating effects on distal steps in the
      stimulus-secretion coupling. The use of calmidazolium offers possibilities to
      investigate the mechanisms activating exocytosis under conditions where the
      cytoplasmic-free Ca2+ concentration does not increase.

PMID- 7649281
TI  - Molecular cloning and sequence analysis of human preprocathepsin C.
AB  - A cDNA clone (C1) coding for human preprocathepsin C was isolated from a human
      ileum cDNA library using a rat kidney-derived RT-PCR probe and its complete
      nucleotide sequence determined. The full-length 1857 bp sequence codes for a
      protein of 463 amino acid residues with a calculated molecular mass of 51848 Da.
      Comparison of the deduced amino acid sequence with that of rat preprocathepsin C
      indicates an 87.5% identity. A multiple alignment of the deduced cathepsin C
      sequence of 233 residues which, by analogy to other cystein proteinases,
      corresponds to the mature protein, confirms that human cathepsin C belongs to the
      papain superfamily.

PMID- 7649282
TI  - Expression of Aequorea green fluorescent protein in plant cells.
AB  - The coding region of the green fluorescent protein (GFP) from Aequorea victoria
      has been fused to the cauliflower mosaic virus 35S promoter and introduced into
      maize leaf protoplasts. Transient expression of GFP was observed. In addition,
      the coding region of GFP was fused to an Arabidopsis heat shock promoter and co
      transformed with another construct in which GFP has been replaced with
      chloramphenicol acetyltransferase (CAT). The heat-induced expression of GFP in
      maize protoplasts parallels that of CAT. While GFP was expressed in both dark
      grown and green maize leaf protoplasts, no green fluorescence was observed in
      similarly transformed Arabidopsis protoplasts.

PMID- 7649283
TI  - Expression in mammalian cells, purification and characterization of recombinant
      human pancreatic ribonuclease.

PMID- 7649285
TI  - Inhibition of cruzipain, the major cysteine proteinase of the protozoan parasite,
      Trypanosoma cruzi, by proteinase inhibitors of the cystatin superfamily.
AB  - Cruzipain, the major cysteine proteinase from Trypanosoma cruzi epimastigotes,
      purified to a sequentially pure form, exists in multiple forms with pI values
      between 3.7 and 5.1, and an apparent molecular mass of 41 kDa. The enzyme is
      stable between pH 4.5-9.5. Cruzipain was found to be rapidly and tightly
      inhibited by various protein inhibitors of the cystatin superfamily (kass = 1.7
      79 x 10(6) M-1s-1, Kd = 1.4-72 pM). These results suggest a possible defensive
      role for the host's cystatins after parasite infection, and may be of use for the
      design of new therapeutic drugs.

PMID- 7649286
TI  - Does DNA acid fixation produce left-handed Z structure?
AB  - The effects of acetic acid (HCOOCH3) on the solution structure of calf-thymus DNA
      are studied at pH 7.3-2.5 with acid/DNA(P) (phosphate) molar ratios (r) of 1/40,
      1/20, 1/10, 1, 2, 10, 20 and 40. Fourier Transform infrared (FTIR) difference
      spectroscopy is used to establish correlations between spectral changes and base
      protonation, DNA conformational transition and structural variations of the acid
      DNA complexes in aqueous solution. The FTIR difference spectroscopic results
      showed that protonation of cytosine and subsequent unpairing of the G-C base
      pairs begins at pH 4-3 and continues up to pH 2.5, where a complete base
      separation and base unstacking occur. Similarly, protonation of A-T base pairs
      starts at pH 4-3 and is completed at pH 2.5, where base separation and base
      unstacking are observed. The protonation of the G-C base pair leads to the
      formation of Hoogsteen-type H-bonding, before a complete G-C disruption. The
      biopolymer protonation leads to the formation of several non-B-DNA structures,
      including left-handed Z conformation.

PMID- 7649284
TI  - Proposed cation-pi mediated binding by factor Xa: a novel enzymatic mechanism for
      molecular recognition.
AB  - Factor Xa (FXa) is an important serine protease in the blood coagulation cascade.
      Small synthetic competitive inhibitors of FXa are under development as potential
      anticoagulants. To better understand FXa structural features and molecular
      recognition mechanisms, we have constructed three dimensional models of FXa
      inhibitor complex structures via a new search approach that samples
      conformational space and binding space simultaneously for DABE and DX-9065a, two
      bis amidinoaryl derivatives that are among the most potent and selective FXa
      inhibitors reported to date. We find the most probable binding modes for the two
      inhibitors to be a folded conformation, with one distal amidino group extending
      into the S1 pocket, forming a salt-bridge with FXa Asp-189, and the other
      positively charged group fitting into the S4 subsite, and stabilized by a cation
      pi interaction. We propose as a hypothesis that the cavity-like S4 subsite formed
      by the three pi-faces of the aromatic residues Tyr-99, Phe-174 and Trp-215 is
      sufficiently rich in pi electrons that it is not only a hydrophobic pocket, but
      also forms a cation recognition site. This proposed cation-pi binding mechanism
      is one of the first proposed for enzymatic molecular recognition, and for which
      experimental verification can be obtained without any complicating charge
      compensation mechanism. Our models provide plausible explanations of the
      structure-activity relationships observed for these inhibitors, and suggest that
      cation-pi interactions may provide a novel mechanism for molecular recognition.

PMID- 7649287
TI  - Ubiquitination of full-length cyclin.
AB  - Mitotic cyclins are key cell-cycle regulators that are relatively stable through
      most of the cell-cycle then rapidly degraded at mitosis. We have detected
      ubiquitin conjugates of full-length Xenopus cyclin B2 strongly suggesting that
      ubiquitination rather than a proteolytic cleavage is the initiating event in
      cyclin destruction. The highest levels of ubiquitin conjugates correlate with the
      phase of rapid proteolysis. This result supports previous findings that implicate
      the ubiquitin system in cyclin proteolysis. However, we also observe cyclin
      ubiquitin conjugates in both cytostatic factor arrested and interphase extracts
      where cyclin is more stable. The physiologic role of ubiquitinated cyclin under
      these conditions is unclear.

PMID- 7649289
TI  - Selectivity and gating properties of a cAMP-modulated, K(+)-selective channel
      from Drosophila larval muscle.
AB  - The selectivity and gating properties of cAMP-modulated, voltage-independent,
      K(+)-selective channel from Drosophila larval muscle were investigated using the
      patch-clamp technique. In symmetrical 115 mM K+ the channel displayed a linear
      current-voltage relation with slope conductance of 43 pS. Under biionic
      conditions (115 mM K+ pipette/115 mM X+ cytoplasmic) the permeability sequence
      was K+ > Rb+ > NH4+ >> Cs+,Na+. The channel was impermeable to Ca2+ (PCa/PK <
      0.02). Under steady-state conditions and regardless [cAMP], open dwell times
      showed a double exponential distribution. [cAMP] did not affect the time
      constants of the two components of open times, or their relative amplitudes.
      Moreover, successive openings were correlated in open time. Closed dwell times
      were made of at least three exponential components. Fast application of cAMP to
      the cytoplasmic side of the channel induced a transient increase in open
      probability that relaxed to a lower value within seconds. This last result
      suggests that cAMP can activate and desensitize this cAMP-modulated, K(+)
      selective channel.

PMID- 7649288
TI  - cDNA analysis of the mite allergen Lep d 1 identifies two different isoallergens
      and variants.
AB  - For the first time the complete cDNA encoding two isoallergens of the non
      pyroglyphid dust mite Lepidoglyphus destructor, Lep d 1, allergen has been
      sequenced. In addition, one of the isoallergens was found to have two variants.
      Oligonucleotides were designed from known amino acid sequences. The cDNA
      sequences were obtained by hybridizing these primers to mRNA and enhancement by
      the RT-PCR technique. To obtain the different complete encoding cDNA sequences
      and eliminate heteroduplex artifacts, we performed PCR + 1 reactions. Comparison
      of the amino acid sequence of the allergen shows leader sequences of 16 amino
      acids for both isoforms.

PMID- 7649290
TI  - CD45 phosphatase in Jurkat cells is necessary for response to applied ELF
      magnetic fields.
AB  - Oscillations of free intracellular calcium [Ca2+]i were seen in individual Jurkat
      cells as response to a 50 Hz, 0.15 mT magnetic field (MF). In contrast, a CD45
      deficient Jurkat cell line was unable to respond to MF stimulation. The
      phosphatase activity of CD45 has been implicated to regulate p56lck tyrosine
      kinase activity by removing an inhibitory phosphate. By using Jurkat cells that
      expressed a chimeric molecule, comprising the cytoplasmic phosphatase domain of
      CD45, the MF induced calcium response was restored. This showed the necessity for
      an intact signal transduction pathway leading to a calcium increase as a result
      of stimulation of cells by MF. Thus, our data suggest that the target for the
      applied MF are molecules involved in early events in the signalling pathway from
      the T cell antigen receptor.

PMID- 7649291
TI  - Partial restoration of inactivated ribosomes with sodium borohydride or amino
      acids.
AB  - The aldehyde radical of ribose C1' at position 4324 in rat liver 28S rRNA
      generated by RNA N-glycosidase was either reduced to an hydroxyl group by sodium
      borohydride or converted into aldimine through a nucleophilic addition of amino
      acid used as a primary amine. Analysis of the R-fragment of 28S rRNA by
      polyacrylamide gel electrophoresis showed that the reduction of aldehyde to an
      hydroxyl group with sodium borohydride was highly specific. The protein synthesis
      activity of modified ribosomes was partially restored with the removal of the
      active aldehyde by sodium borohydride or amino acid. Reduction of aldehyde with
      sodium borohydride restored 43.1% of the protein synthesis activity. Among the
      twenty natural amino acids tested, tryptophan and histidine could restore 57.4%
      and 42.1% of the ribosome activity when brome mosaic virus RNA was used as mRNA.
      We came to the conclusion that the active aldehyde radical at position 4324 of
      28S rRNA in modified ribosome may cause the inactivation of the ribosome for
      protein synthesis.

PMID- 7649292
TI  - Group II phospholipase A2 activates mitogen-activated protein kinase in cultured
      rat mesangial cells.
AB  - Group II phospholipase A2 (PLA2) is a mediator of inflammation in various disease
      including glomerulonephritis. We recently found that urinary excretion of PLA2
      was increased in patients with mesangial proliferative glomerulonephritis and
      that interleukin-1 (IL-1) enhanced platelet derived growth factor-stimulated
      mesangial cell proliferation through the action of group II PLA2 secreted in
      response to IL-1 stimuli. Here we report signal transducing mechanism through
      group II PLA2 in mesangial cells. Group II PLA2 (1-15 U/ml) rapidly activated
      mitogen-activated protein (MAP) kinase. IL-1 beta activated MAP kinase in two
      phases and the slow activation in the late phase, proceeding in parallel with
      increased group II PLA2 secretion elicited by IL-1 treatment, was inhibited by
      the specific antibody raised against group II PLA2. This suggests that the late
      phase activation of IL-1-induced MAP kinase was mediated, at least in part, by
      secreted group II PLA2.

PMID- 7649293
TI  - A photoreceptor with characteristics of phytochrome triggers sporulation in the
      true slime mould Physarum polycephalum.
AB  - Phytochrome is a ubiquitous photoreceptor in plants that controls a variety of
      responses to light, including gene expression, differential cell growth and
      intracellular movement of organelles. All phytochromes analysed so far are
      reversibly interconverted by light between an inactive and an active
      conformation, each of which has a different and characteristic absorbance
      spectrum. Based on photophysiological measurements we provide evidence, that a
      photoreceptor with these unique properties of phytochrome triggers sporulation in
      the true slime mould Physarum polycephalum.

PMID- 7649294
TI  - DNA binding site of the yeast heteromeric Ino2p/Ino4p basic helix-loop-helix
      transcription factor: structural requirements as defined by saturation
      mutagenesis.
AB  - The inositol/choline-responsive element (ICRE) is an 11 bp cis-activating
      sequence motif with central importance for the regulated expression of
      phospholipid biosynthetic genes in the yeast Saccharomyces cerevisiae. The ICRE
      containing the CANNTG core binding sequence (E-box) of basic helix-loop-helix
      (bHLH) regulatory proteins is recognized by the heteromeric bHLH transcription
      factor Ino2p/Ino4p. In this study, we define the Ino2p/Ino4p consensus binding
      sequence (5'-WYTTCAYR-TGS-3') based on the characterization of all possible
      single nucleotide substitutions. Interestingly, this analysis also identified a
      single functional deviation (CACATTC) from the CANNTG core recognition element of
      bHLH proteins. The DNA binding specificities of different yeast bHLH proteins may
      now be explained by distinct nucleotide preferences especially at two positions
      immediately preceding the CANNTG core motif.

PMID- 7649295
TI  - Solubilization and purification of aldehyde-generating fatty acyl-CoA reductase
      from green alga Botryococcus braunii.
AB  - Membrane-bound fatty acyl-CoA reductase from the green alga Botryococcus braunii
      has been solubilized from the microsomal preparation by 0.1% octyl beta-glucoside
      and purified to near homogeneity by Blue A agarose and palmitoyl-CoA agarose
      affinity column chromatography. The molecular mass of the enzyme was estimated by
      SDS-PAGE to be 35 kDa. The enzyme generates fatty aldehyde by reduction of fatty
      acyl-CoA with NADH as the reductant. The N-terminal amino acid sequence of this
      protein that represents the first eucaryotic aldehyde-generating reductase to be
      purified shows high homology with the N-terminus of fatty acid reductase from
      bacteria.

PMID- 7649296
TI  - Characterization of the DNA triplex formed by d(TGGGTGGGTGGTTGGGTGGG) and a
      critical R.Y sequence located in the promoter of the murine Ki-ras proto
      oncogene.
AB  - The binding of the G-rich oligonucleotide d(TGGGTGGGTGGTTGGGTGGG) to a critical
      homopurine-homopyrimidine sequence located in the promoter of the murine Ki-ras
      proto-oncogene has been investigated. The duplex and the oligonucleotide form a
      triple helix as evidenced by band-shift electrophoresis, hydroxyapatite (HA)
      chromatography, UV-melting and circular dichroism (CD) experiments. Upon thermal
      denaturation in 50 mM Tris-acetate, pH 7.4, 50 mM NaCl, 10 mM MgCl2, 0.1 mM
      spermine the triplex exhibits two cooperative transitions: one of these is
      attributed to the triplex-to-duplex transformation, the other to the duplex-to
      coil transformation. The thermodynamic parameters of triplex formation have been
      determined by a van't Hoff analysis of the UV-melting curves which provided
      values of delta H = 79 +/- 8 kcal/mol, delta S = 224 +/- 22 e.u., delta G298 =
      12.2 +/- 1.2 kcal/mol. These data are compared with those reported for the YRY
      triplex motif.

PMID- 7649297
TI  - From triple cysteine mutants to the cysteine-less glucose transporter GLUT1: a
      functional analysis.
AB  - Two triple cysteine mutants containing Cys-less N- or C-terminal halves and the
      Cys-less GLUT1 were generated by site-directed mutagenesis. Following expression
      in Xenopus oocytes, the intrinsic transport activities of the multiple cysteine
      mutants were slightly decreased when either the cysteine residues of the C
      terminal half or all six residues were changed; substitution of serine for
      cysteine residues located at the N-terminal half was without consequence for the
      catalytic activity. The exofacial ligand ethylidene glucose inhibited 2-deoxy-D
      glucose uptake of wild-type and Cys-less GLUT1-expressing Xenopus oocytes with
      comparable half-saturation constants (11.5 and 13.2 mM). However, each of the
      multiple cysteine mutants exhibited an increase in affinity for the endofacial
      inhibitor cytochalasin B, with the greatest effect being observed for the Cys
      less construct (decrease in Ki by the factor 5-6).

PMID- 7649298
TI  - Class III alcohol dehydrogenase from Saccharomyces cerevisiae: structural and
      enzymatic features differ toward the human/mammalian forms in a manner consistent
      with functional needs in formaldehyde detoxication.
AB  - Alcohol dehydrogenase class III (glutathione-dependent formaldehyde
      dehydrogenase) from Saccharomyces cerevisiae was purified and analyzed
      structurally and enzymatically. The corresponding gene was also analyzed after
      cloning from a yeast genome library by screening with a probe prepared through
      PCR amplification. As with class III alcohol dehydrogenase from other sources,
      the yeast protein was obtained in two active forms, deduced to reflect different
      adducts/modifications. Protein analysis established N-terminal and C-terminal
      positions, showing different and specific patterns in protein start positions
      between the human/mammalian, yeast, and prokaryotic forms. Km values with
      formaldehyde differ consistently, being about 10-fold higher in the yeast than
      the human/mammalian enzymes, but compensated for by similar changes in kcat
      values. This is compatible with the different functional needs, emphasizing low
      formaldehyde concentration in the animal cells but efficient formaldehyde
      elimination in the microorganisms. This supports a general role of the enzyme in
      formaldehyde detoxication rather than in long-chain alcohol turnover.

PMID- 7649299
TI  - The importance of the GTP-binding protein tissue transglutaminase in the
      regulation of cell cycle progression.
AB  - Tissue transglutaminase (tTgase) is a GTP-binding Ca(2+)-dependent enzyme which
      catalyses the post-translational modification of proteins via epsilon(gamma
      glutamyl) lysine bridges. Recent evidence suggests that the GTP-binding activity
      of tTgase may be important in intracellular signaling thus explaining some of the
      diverse suggested roles for the enzyme. In the following work a malignant hamster
      fibrosarcoma (Met B) has been stably transfected with both the full length tTgase
      cDNA (wild type) and a mutant form of the cDNA whereby the active site cysteine
      (Cys 277) has been replaced by serine. Expression of this mutant cDNA leads to a
      protein with GTP binding activity which is deficient of protein crosslinking
      activity. When synchronised into S-phase and allowed to progress through the cell
      cycle tTgase transfected clones (both mutant and wild type), when compared to
      transfected controls, show a delayed progression from S-phase to G2/M when
      analysed by flow cytometry which appears to be elicited by the G-protein activity
      of the tTgase.

PMID- 7649300
TI  - Alternative splicing of the human Shaker K+ channel beta 1 gene and functional
      expression of the beta 2 gene product.
AB  - Mammalian voltage-activated Shaker K+ channels associate with at least three
      cytoplasmic proteins: Kv beta 1, Kv beta 2 and Kv beta 3. These beta subunits
      contain variable N-termini, which can modulate the inactivation of Shaker alpha
      subunits, but are homologous throughout an aldo-keto reductase core. Human and
      ferret beta 3 proteins are identical with rat beta 1 throughout the core while
      beta 2 proteins are not; beta 2 also contains a shorter N-terminus and has no
      reported physiological role. We report that human beta 1 and beta 3 are derived
      from the same gene and that beta 2 modulates the inactivation properties of Kv1.4
      alpha subunits.

PMID- 7649301
TI  - Action of nitric oxide as an antioxidant against oxidation of soybean
      phosphatidylcholine liposomal membranes.
AB  - To elucidate the protective role of nitric oxide (NO) against lipid peroxidation,
      the effect of NO donor on the formation of lipid hydroperoxide and consumption of
      alpha-tocopherol in the oxidation of soybean phosphatidylcholine liposomal
      membranes was studied. The oxidation was induced by either aqueous or lipophilic
      peroxyl radicals generated by the hydrophilic or lipophilic azo compound,
      respectively. It was found that NO acted as a potent antioxidant by scavenging
      peroxyl radicals rapidly. It was also found that NO was capable of penetrating
      multilamellar membranes to scavenge lipid peroxyl radicals and spare alpha
      tocopherol.

PMID- 7649302
TI  - Glycoprotein biosynthesis in Saccharomyces cerevisiae: ngd29, an N-glycosylation
      mutant allelic to och1 having a defect in the initiation of outer chain
      formation.
AB  - Outer chain glycosylation in Saccharomyces cerevisiae leads to heterogeneous and
      immunogenic asparagine-linked saccharide chains containing more than 50 mannose
      residues on secreted glycoproteins. Using a [3H]mannose suicide selection
      procedure a collection of N-glycosylation defective mutants (designated ngd) was
      isolated. One mutant, ngd29, was found to have a defect in the initiation of the
      outer chain and displayed a temperature growth sensitivity at 37 degrees C
      allowing the isolation of the corresponding gene by complementation. Cloning,
      sequencing and disruption of NGD29 showed that it is a non lethal gene and
      identical to OCH1. It complemented both the glycosylation and growth defect.
      Membranes isolated from an ngd29 disruptant or an ngd29mnn1 double mutant were no
      longer able, in contrast to membranes from wild type cells, to transfer mannose
      from GDPmannose to Man8GlcNAc2, the in vivo acceptor for building up the outer
      chain. Heterologous expression of glucose oxidase from Aspergillus niger in an
      ngd29mnn1 double mutant produced a secreted uniform glycoprotein with exclusively
      Man8GlcNAc2 structure that in wild type yeast is heavily hyperglycosylated. The
      data indicate that this mutant strain is a suitable host for the expression of
      recombinant glycoproteins from different origin in S. cerevisiae to obtain
      mammalian oligomannosidic type N-linked carbohydrate chains.

PMID- 7649303
TI  - The solution structure of the active domain of CAP18--a lipopolysaccharide
      binding protein from rabbit leukocytes.
AB  - We have employed the circular dichroism (CD) technique to characterize the
      solution structure of CAP18(106-137), a lipopolysaccharide (LPS) binding,
      antimicrobial protein, and its interaction with lipid A. Our results revealed
      that CAP18(106-137) may exist in at least three lipid A concentration-dependent,
      primarily helix conformations. The 'model' structure of CAP18(106-137) in 30%
      (v/v) TFE, determined by nuclear magnetic resonance (NMR) technique, was found to
      be a complete and very rigid helix. In this conformation, the cationic and
      hydrophobic groups of CAP18(106-137) are separated into patches and stripes in
      such a way that it can favorably interact with lipid A through either coulombic
      interaction with the diphosphoryl groups or hydrophobic interaction with the
      fatty acyl chains.

PMID- 7649304
TI  - The site of the redox-linked proton pump in eukaryotic cytochrome c oxidases.
AB  - The electronic spectra of fully oxidized derivatives of some cytochrome c oxidase
      preparations are distinctly pH dependent. In general, the observed spectral
      shifts are greater in the case of pulsed derivatives compared to resting
      preparations and also, greater for preparations of the enzyme from shark skeletal
      muscle compared to beef heart. The low temperature near-infrared magnetic
      circular dichroism spectrum of the fully oxidized shark enzyme is not pH
      dependent in the experimental range, indicating the sensitivity of the visible
      region electronic spectrum to variation in pH to be due principally to changes at
      the heme a3-CuB chromophore. The results are discussed in relation to proposed
      mechanisms of proton translocation in cytochrome c oxidase.

PMID- 7649305
TI  - C-type natriuretic peptide and brain natriuretic peptide inhibit adenylyl cyclase
      activity: interaction with ANF-R2/ANP-C receptors.
AB  - C-type natriuretic peptide (CNP) and brain natriuretic peptide (BNP) are members
      of the natriuretic peptide family, which have been shown to interact with ANP
      C/ANF-R2 receptors in addition to ANP-B receptor subtypes. The present study was
      undertaken to investigate if the interaction of CNP and BNP with ANP-C receptors
      results in the inhibition of adenylyl cyclase activity. CNP and BNP inhibited
      adenylyl cyclase activity in heart and brain striatal membranes in a
      concentration dependent manner with an apparent Ki between 0.1 and 1.0 nM.
      Maximal inhibition observed in heart membranes were about 25% and 35% for BNP and
      CNP respectively, however the inhibitions in brain striatal membranes were
      smaller (approximately 20%). The inhibition was dependent on the presence of
      guanine nucleotides and was attenuated by pertussis toxin treatment. In addition,
      CNP inhibited the stimulatory effect of isoproterenol on adenylyl cyclase,
      whereas CNP as well as BNP showed an additive effect with the inhibitory response
      of angiotensin II on adenylyl cyclase activity. When the combined effect of C
      ANF4-23/BNP, C-ANF4-23/CNP and BNP/CNP at optimal concentrations was studied
      together on adenylyl cyclase activity, the percent inhibition remained the same
      for C-ANF4-23 and BNP or C-ANF4-23 and CNP, however, an additive inhibitory
      effect was observed for BNP and CNP. These results suggest that CNP and BNP like
      C-ANF4-23 interact with ANP-C receptors and result in the inhibition of adenylyl
      cyclase activity. On the other hand, CNP and BNP interact with the ANP-C
      receptor, however, the interaction may be different sites or there may be two
      subpopulations of ANP-C receptors specific for each of the peptides. These
      results indicate that BNP and CNP, like ANP and C-ANF4-23, inhibit the adenylyl
      cyclase/cAMP signal transduction system through an inhibitory guanine nucleotide
      regulatory protein, by interacting with ANP-C receptor subtypes.

PMID- 7649306
TI  - The targeting information of the mitochondrial outer membrane isoform of
      cytochrome b5 is contained within the carboxyl-terminal region.
AB  - Two isoforms of mammalian cytochrome b5, which have homologous cytosolic amino
      terminal catalytic domains, are located one on endoplasmic reticulum (ER b5) the
      other on mitochondrial outer membranes (OM b5). A cDNA coding for the previously
      unknown carboxyl-terminal domain of OM b5 was cloned and a chimera between the
      catalytic domain of ER b5 and the carboxyl-terminal region of OM b5 was expressed
      in cultured mammalian cells. The chimera localized to mitochondria, indicating
      that the carboxyl-terminal 43 amino acids of OM b5 contain sufficient information
      to target the catalytic domain of ER b5 to the mitochondrial outer membrane.

PMID- 7649307
TI  - Function of Pro-185 in the ProCys of conserved motif IV in the EcoRII [cytosine
      C5]-DNA methyltransferase.
AB  - ProCys in the conserved sequence motif IV of [cytosine-C5]-DNA methyltransferases
      is known to be part of the catalytic site. The Cys residue is directly involved
      in forming a covalent bond with the C6 of the target cytosine. We have found that
      substitution of Pro-185 with either Ala or Ser resulted in a reduced rate of
      methyl group transfer by the EcoRII DNA methyltransferase. In addition, we
      observed an increase in the Km for substrate S-adenosyl-L-methionine (AdoMet),
      but a decrease in the Km for substrate DNA. This is reflected in minor changes in
      kcat/Km for DNA, but in 10- to 100-fold reductions in kcat/Km for AdoMet. This
      suggests that Pro-185 is important to properly orient the activated cytosine and
      AdoMet for methyl group transfer by direct interaction with AdoMet and indirectly
      via the Cys interaction with cytosine.

PMID- 7649308
TI  - Secretion and processing mechanisms of procathepsin L in bone resorption.
AB  - Secretion of procathepsin L into the culture medium from a bone cell mixture was
      markedly enhanced by addition of parathyroid hormone (PTH), 1 alpha,25-(OH)2D3 or
      tumor necrosis factor alpha (TNF alpha). These stimulators of secretion of
      procathepsin L enhanced bone pit formation, which was inhibited by E-64, but not
      by CA-074, a specific inhibitor of cathepsin B. Procathepsin L may thus
      participate in the process of bone collagenolysis during bone resorption.
      Procathepsin L partially purified from rat long bones under cold conditions was
      rapidly converted to the mature form under acidic conditions at room temperature.
      This conversion was inhibited by E-64, suggesting that the procathepsin L
      secreted into lacunae is catalytically converted to the mature enzyme by cysteine
      proteinase(s).

PMID- 7649309
TI  - Energy-dependent Complex I-associated ubisemiquinones in submitochondrial
      particles.
AB  - Two distinct species of Complex I-associated ubisemiquinones (SQNf and SQNs) were
      detected by cryogenic EPR analysis of tightly coupled submitochondrial particles
      oxidizing NADH or succinate under steady-state conditions. The g = 2.00 signals
      from both fast-relaxing SQNf (P1/2 = 170 mW at 40 K) and slow-relaxing SQNs (P1/2
      = 0.7 mW) are sensitive to uncouplers, rotenone and thermally induced
      deactivation of Complex I. At higher temperatures the SQNf signal is broadened
      and only the SQNs signal is seen (P1/2 = 7 mW at 105 K). The spin-spin
      interaction between SQNf and the iron-sulfur cluster N2 was detected as split
      peaks of the g parallel 2.5 signal with a coupling constant of 1.65 mT, revealing
      their mutual distance of 8-11 A. The data obtained are consistent with a model in
      which N2 and two interacting bound ubisemiquinone species are spatially arranged
      within the hydrophobic domain of Complex I, participating in the vectorial proton
      translocation.

PMID- 7649310
TI  - FTIR spectroscopy shows weak symmetric hydrogen bonding of the QB carbonyl groups
      in Rhodobacter sphaeroides R26 reaction centres.
AB  - The absorption frequencies of the C = O and C = C (neutral state) and of the
      C...O (semiquinone state) stretching vibrations of QB have been assigned by FTIR
      spectroscopy, using native and site-specifically 1-, 2-, 3- and 4-13C-labelled
      ubiquinone-10 (UQ10) reconstituted at the QB binding site of Rhodobacter
      sphaeroides R26 reaction centres. Besides the main C = O band at 1641 cm-1, two
      smaller bands are observed at 1664 and 1651 cm-1. The smaller bands at 1664 and
      1651 cm-1 agree in frequencies with the 1- and 4-C = O vibrations of unbound
      UQ10, showing that a minor fraction is loosely and symmetrically bound to the
      protein. The larger band at 1641 cm-1 indicates symmetric H-bonding of the 1- and
      4-C = O groups for the larger fraction of UQ10 but much weaker interaction as for
      the 4-C = O group of QA. The FTIR experiments show that different C = O protein
      interactions contribute to the factors determining the different functions of
      UQ10 at the QA and the QB binding sites.

PMID- 7649311
TI  - Alteration in relative activities of phenylalanine dehydrogenase towards
      different substrates by site-directed mutagenesis.
AB  - Glycine-124 and leucine-307 of phenylalanine dehydrogenase from Bacillus
      sphaericus were altered by site-specific mutagenesis to the corresponding
      residues in leucine dehydrogenase: alanine and valine, respectively. These two
      residues have previously been implicated from molecular modelling as important in
      determining the substrate discrimination of the two enzymes. Single and double
      mutants displayed lower activities towards L-phenylalanine and enhanced activity
      towards almost all aliphatic amino acid substrates tested compared to the wild
      type, thus confirming the predictions made from molecular modelling.

PMID- 7649312
TI  - Comparative analysis of catalases: spectral evidence against heme-bound water for
      the solution enzymes.
AB  - A recent X-ray structural analysis of M. luteus catalase indicates heme-bound H2O
      trans to the proximal tyrosinate ligand, a finding in contrast to previous X-ray
      data reporting a 5-coordinate heme for bovine liver catalase. The presence of
      heme-bound H2O, requiring displacement prior to substrate-binding, is likely to
      be catalytically significant for catalases. We have used magnetic circular
      dichroism (MCD) spectroscopy, a highly accurate method for assignment of heme
      spin- and coordination-states, to study native, solution forms of bovine liver,
      M. luteus, and A. niger catalases. All three enzymes display similar spectral
      features with the weak (approximately 5 delta epsilon M [moles.cm.Tesla]-1)
      intensity typical of a 5-coordinate high-spin ferric heme. No evidence for H2O
      ligation, inducing a 6-coordinate heme, occurred upon variation of pH or buffer
      composition. Therefore, we suggest that the catalytically significant structure
      of catalases has an unoccupied heme binding site trans to the proximal tyrosinate
      heme ligand.

PMID- 7649313
TI  - XIV World Congress of Gynecology and Obstetrics (FIGO) 1994. Montreal, Canada,
      Sept. 26-30, 1994. Abstracts.

PMID- 7649314
TI  - Endoscopic surgery in gynecologic practice.
AB  - In recent decades, the operative approach for several gynecologic diseases has
      changed from laparotomy to laparoscopy. New techniques and indications are
      continuously being developed. Laparoscopy offers a lot of advantages for the
      patient, but still a lot of additional data are required to determine the exact
      indications. Operative laparoscopy requires not only skill and experience, but
      also specialized equipment and paramedical staff. The most important topics for
      the gynecologist will be reviewed in this article.

PMID- 7649316
TI  - Control of gestational diabetes.
AB  - OBJECTIVE: The purpose of the study was to determine the best regimen for
      metabolic control of gestational diabetes. METHODS: A prospective study was
      conducted over a period of 5 years in 355 diabetic women delivered at the King
      Fahd Hospital of the University, Al-Khobar, Saudi Arabia, between January 1987
      and December 1991. The patients were divided into three groups according to their
      mean plasma glucose levels during pregnancy: good control was defined as a mean
      plasma glucose level of less than 120 mg/dl (group A); moderate control as a mean
      plasma glucose level between 120 and 140 mg/dl (group B); and poor control as a
      mean plasma glucose level in excess of 140 mg/dl (group C). The t-test was used
      for statistical analysis. RESULTS: Antenatal and neonatal complications were much
      higher in groups B and C than in group A, the overall complication rate being
      five times higher in group C than in group A. CONCLUSION: The data indicate that
      good glycemic control is one determinant of maternal and fetal complications in
      pregnancies complicated by gestational diabetes.

PMID- 7649315
TI  - Labetalol vs. methyldopa in the treatment of pregnancy-induced hypertension.
AB  - OBJECTIVE: To assess the efficacy and safety of labetalol compared with
      methyldopa in the management of mild and moderate cases of pregnancy-induced
      hypertension (PIH). METHODS: One hundred four primigravidas with PIH were
      randomly allocated to receive either labetalol (group A) or methyldopa (group B).
      The dose of the drugs was doubled every 48 h to maintain a mean arterial blood
      pressure < or = 103.6 mmHg. Clinico-biochemical effects and frequency of side
      effects were studied. The statistical level of significance was taken at P <
      0.05. RESULTS: Ten patients in group B (18.5%) developed significant proteinuria
      (> 30 mg/dl) whereas none developed proteinuria in group A. Labetalol was quicker
      and more efficient at controlling blood pressure, having a beneficial effect on
      renal functions and causing fewer side effects compared with methyldopa. The rate
      of induction of labor and rate of cesarean section for uncontrolled PIH was less
      in group A (48% and 1%, respectively) compared with group B (63.0% and 5.6%,
      respectively). Moreover a higher Bishop score at induction of labor was noticed
      in group A. CONCLUSIONS: Labetalol is better tolerated than methyldopa, gives
      more efficient control of blood pressure and may have a ripening effect on the
      uterine cervix.

PMID- 7649317
TI  - Impact of maternal HIV-1 infection on perinatal outcome.
AB  - OBJECTIVES: To study the impact of HIV-1 infection on pregnancy and maternal and
      early fetal outcome. METHOD: From January 1992 to January 1993, 160 HIV-1
      seropositive women and 164 HIV-1 seronegative age- and parity-matched pregnant
      tribal women from Manipur, India, were recruited into a prospective study. Mother
      and infant were followed until 6 weeks postpartum. RESULTS: Nine percent (15/160)
      of subjects had AIDS (CDC IV), 38% (60/160) were symptomatic (CDC III) and 53%
      (85/160) were asymptomatic (CDC I/II). Symptomatic (CDC III/IV) HIV-1 infection
      is associated with a significantly increased rate of miscarriage, low birth
      weight, intrauterine fetal death and preterm delivery. Perinatal, infant and
      maternal deaths were limited to symptomatic women. HIV-1 infected women were
      significantly younger than their HIV-1 negative counterparts both in age and age
      at sexual debut. Placental membrane inflammation was significantly higher in the
      seropositive group and this correlated well with a higher risk of preterm
      delivery and postpartum endometritis. Asymptomatic HIV-1 infection was not
      associated with adverse pregnancy outcome. CONCLUSION: Symptomatic (CDC III/IV)
      HIV-1 infection in Indian tribal women is associated with adverse maternal and
      fetal outcome.

PMID- 7649318
TI  - Postdate antenatal testing.
AB  - OBJECTIVE: To test the effect on pregnancy outcome of a policy of very early
      commencement of postdate surveillance testing, and induction of labor at 42
      weeks. METHODS: Retrospective analysis of 2776 consecutive cephalic deliveries at
      38-42 weeks of gestation. Management of the postdate pregnancies included twice
      weekly antenatal testing beginning at 40 completed weeks and elective induction
      of labor at 42 completed weeks. Pregnancy outcome parameters were compared
      between the groups delivered at 38-40 weeks and at 41-42 weeks. RESULTS: There
      were 2138 pregnancies delivered at 38-40 weeks and 638 at 41-42 weeks. The latter
      group had a statistically significant increase in the rate of cesarean section,
      mainly accounted for by an increased rate of fetal distress and failure to
      progress in labor. Similarly the rate of instrumental vaginal delivery, meconium
      in labor and macrosomia had a statistically significantly higher incidence in the
      postdate group. These differences in outcome were already apparent at 41 weeks of
      gestation. CONCLUSION: Despite early initiation of fetal surveillance, starting
      at 40 completed weeks, postdate pregnancies are associated with an increased rate
      of emergency cesarean section, macrosomia and meconium in labor.

PMID- 7649319
TI  - Low-dose vaginal misoprostol for induction of labor with a live fetus.
AB  - OBJECTIVE: To test the effectiveness and safety of low-dose vaginal misoprostol
      for induction of labor with a live fetus. METHODS: Labor was induced in 666
      pregnant women with a live fetus in the cephalic position, who had no medical
      complications and no history of uterine surgery. One-fourth of a 200-micrograms
      tablet of misoprostol (50 micrograms) was placed in the posterior vaginal fornix
      every 12 h for a maximum of four doses or until active labor commenced. Time from
      induction to delivery, side effects and neonatal outcome were evaluated. RESULTS:
      Labor was successfully induced in all cases. The mean time from induction to
      delivery was 10.4 h. The cesarean section rate was 7.8%. There were eight
      perinatal deaths, six of which occurred in low birth weight fetuses. There was
      one case of abruptio placenta, which was less than that expected in the study
      population. CONCLUSION: Vaginal misoprostol, in very low doses, was a remarkably
      efficient and safe method for induction of labor with a live fetus.

PMID- 7649320
TI  - Reproductive outcome following abdominal metroplasty.
AB  - OBJECTIVE: To evaluate pregnancy outcome following uterine unification procedures
      in patients with uterine anomalies. METHODS: A retrospective survey included all
      abdominal metroplasty procedures performed on 43 patients at the American
      University of Beirut Medical Center between January 1, 1974 and December 31,
      1991. Age at metroplasty, type of anomaly and surgical procedures, as well as
      preoperative and postoperative reproductive performance were all recorded.
      RESULTS: Forty (93%) out of 43 patients who underwent metroplasty had
      postoperative live births compared with five (12%) prior to surgery. The fetal
      wastage rate dropped from 93% pre- to 16% postoperatively. All seven patients
      with a history of primary infertility conceived and had live births. CONCLUSION:
      Our data suggest a remarkable improvement following abdominal metroplasty in
      patients with both typical and uncharacteristic preoperative reproductive
      performance.

PMID- 7649321
TI  - Surgical classification of obstetric fistulas.
AB  - OBJECTIVE: To develop a surgical classification for obstetric fistulas in order
      to compare surgical techniques and results. METHODS: Based on a retrospective
      analysis of 775 consecutive fistula patients, the following classification is
      presented: (type I) fistulas not involving the urethral closing mechanism; (type
      II) fistulas involving the urethral closing mechanism; and (type III) ureter and
      other exceptional fistulas. Type II fistulas can be further divided into: (A)
      without (sub)total urethra involvement, and (B) with (sub)total urethra
      involvement; and (a) without a circumferential defect, and (b) with a
      circumferential defect. This classification was applied prospectively in over
      2700 consecutive fistula patients. RESULTS: The surgical technique becomes
      progressively more complicated from type I through type IIBb. The results of
      closure and continence worsen progressively from type I through type IIBb.
      Personal experience in the case of type III fistulas is very limited. CONCLUSION:
      This classification enables a systematic comparison of different surgical
      techniques and an objective evaluation of results from different centers.

PMID- 7649322
TI  - Menopausal genuine stress urinary incontinence treated with conjugated estrogens
      plus progestogens.
AB  - OBJECTIVE: The aim of the study was to investigate clinically and urodynamically
      the effects of hormonal replacement in the treatment of genuine stress urinary
      incontinence in postmenopausal females. METHODS: Clinical and urodynamic
      variables of 30 postmenopausal women with genuine stress urinary incontinence
      were evaluated after 3 months' treatment with conjugated estrogens plus
      progestogens. Urodynamic evaluations were performed in all patients before and
      after treatment. RESULTS: Forty-six percent of the patients treated medically
      were judged to be cured and 43% were judged to be markedly improved. Maximum
      urethral closure pressure, maximum cystometric capacity and mean flow were
      significantly increased. Residual urine and diurnal and nocturnal voluntary
      micturition were markedly decreased (P < 0.05). CONCLUSION: We conclude that
      hormone replacement in the form of conjugated estrogens plus progestogens results
      in the clinical and urodynamic improvement of genuine stress urinary incontinence
      in postmenopausal women.

PMID- 7649323
TI  - Interferon as an adjuvant treatment for genital condyloma acuminatum.
AB  - OBJECTIVE: To evaluate the effect of alpha-interferon as an adjuvant to laser or
      fluorouracil treatment in patients with recurrent genital human papillomavirus
      (HPV) infection. METHODS: Sixty-two females and 21 males were treated for
      recurrent HPV infection, with either fluorouracil (Efudex 5%) cream or laser
      ablation of the lesions. Half of the patients were then randomly treated with
      adjuvant alpha-interferon, to the lesions for patients treated with fluorouracil,
      or beneath areas previously treated by laser, once a week, for 8 weeks. The other
      half of the patients did not receive interferon adjuvant. Evaluation of both
      groups was done using colposcopy and acetic acid, to assess recurrence rates up
      to 1 year after treatment. RESULTS: Of the 83 patients followed for 1 year,
      colposcopy revealed recurrent anogenital lesions in 3 of 45 receiving interferon,
      compared with 9 of 38 patients treated without adjuvant interferon. CONCLUSION:
      Interferon is effective as adjuvant treatment in controlling the recurrence of
      genital HPV.

PMID- 7649324
TI  - Carcinoma of the uterine cervix associated with schistosomiasis and induced by
      human papillomaviruses.
AB  - OBJECTIVES: To determine the presence of human papillomaviruses (HPVs) in
      cervical cancer among patients in Tanzania and to ascertain their prevalence in
      cases associated with schistosomiasis. METHODS: In situ hybridization was applied
      to 31 carcinomas of the uterine cervix including 10 in which schistosomiasis co
      occurred. Twenty-six cases in this series also exhibited koilocytic dysplasia.
      RESULTS: Twenty-six out of 31 cases revealed a specific hybridization for HPVs
      with varying density and distribution. A slightly higher labeling of HPV-16 than 
      18 was demonstrated. All schistosomiasis-associated cancers encoded the
      papillomaviruses. The 31 patients were predominantly young adults, a fact that
      reflects sexual activity at a very young age in the ethnic communities of Africa.
      CONCLUSION: These findings shed new light on the presumed etiologic implication
      of schistosomiasis in the genesis of cervical cancer. In the absence of HPV,
      schistosomiasis is not the oncogenic causative agent for carcinoma of the uterine
      cervix.

PMID- 7649326
TI  - Swyer syndrome: an unusual presentation.
AB  - We report a 27-year-old XY female who presented with abdominal pain due to
      hemoperitoneum from a ruptured abdominal mass. Gonadoblastoma overgrown by
      endodermal sinus tumor and dysgerminoma was detected. The risk of neoplasia in
      such cases is discussed.

PMID- 7649327
TI  - Fraser syndrome.
AB  - In a consanguineous marriage, a woman at 32 weeks' pregnancy presented with
      intrauterine growth retardation and bilateral renal agenesis. Fraser syndrome
      (cryptophthalmus syndactyly syndrome) was diagnosed based on cryptophthalmos,
      atresia of meatus acusticus externus in auricula, syndactyly, hypoplastic larynx,
      hypoplastic left lung, agenesis of urinary system and aberrant pancreas in
      duodenum. The syndrome is inherited as a recessive trait and the risk of
      recurrence is 25%.

PMID- 7649325
TI  - Balloon valvuloplasty during pregnancy.
AB  - Although rheumatic diseases are reported to be almost eradicated in the developed
      countries, they still continue to contribute significantly to maternal mortality
      in the developing world. Surgical therapies need to be considered for those
      patients who do not respond satisfactorily to medication. However, valve
      replacement or valvulotomy during pregnancy carries significant risks for both
      the mother and the fetus. Two patients with severe mitral stenosis refractory to
      medical therapy are presented. Both patients were subjected to percutaneous
      balloon valvuloplasty during pregnancy without any complications. They were able
      to discontinue medication and deliver vaginally at term. Balloon valvuloplasty
      appears to be a safe alternative to conventional surgical approaches in
      pregnancy.

PMID- 7649328
TI  - Age of menopause of Chinese women in Taiwan.

PMID- 7649330
TI  - Transvaginal pulsed and color Doppler imaging for the evaluation of benign and
      malignant uterine tumors.

PMID- 7649329
TI  - Pseudo-Meigs' syndrome and lupus.

PMID- 7649331
TI  - Induced abortion in Ilorin, Nigeria.

PMID- 7649332
TI  - Splenic artery aneurysm rupture in the second trimester.

PMID- 7649333
TI  - ACOG technical bulletin. Hyperandrogenic chronic anovulation. Number 202-
      February 1995. Committee on Technical Bulletins of the American College of
      Obstetricians and Gynecologists.
AB  - The evaluation and treatment of chronic anovulation requires knowledge of the
      many disorders which may present as menstrual abnormalities. The evaluation
      should document physical findings suggestive of androgen excess. Initial
      evaluation includes an orderly approach to laboratory testing. Underlying
      disorders may include life-threatening diagnoses. The goals of therapy include
      correction of life-threatening disorders, protection of endometrial health,
      preservation or restoration of fertility, and reversal of cosmetically disturbing
      hirsutism.

PMID- 7649334
TI  - ACOG committee opinion. Female genital mutilation. Number 151--January 1995.
      Committee on Gynecologic Practice. Committee on International Affairs. American
      College of Obstetricians and Gynecologists.

PMID- 7649335
TI  - ACOG committee opinion. Recommendations on frequency of Pap test screening.
      Number 152--March 1995. Committee on Gynecologic Practice. American College of
      Obstetricians and Gynecologists.

PMID- 7649336
TI  - ACOG committee opinion. Absence of endocervical cells on a Pap test. Number 153-
      March 1995. Committee on Gynecologic Practice. American College of Obstetricians
      and Gynecologists.

PMID- 7649337
TI  - Intrapartum surveillance: recommendations on current practice and overview of new
      developments. FIGO Study Group on the Assessment of New Technology. International
      Federation of Gynecology and Obstetrics.

PMID- 7649338
TI  - Identifying the patient with heart failure.
AB  - Heart failure is becoming an increasing concern to healthcare worldwide, and of
      particular concern in the Western world where the age of the population continues
      to rise. Furthermore, it has now become clear that, if heart failure is
      identified and treated in the earliest stages of ventricular dysfunction, the
      possibility of recovery from or substantial delay in progression to complete
      heart failure is extremely good and will give the patient a considerably improved
      quality of life. Certain signs and symptoms found on routine examination, coupled
      with knowledge of patient history, can indicate early heart failure. Patients
      will normally present to their family practitioner, who is likely to have long
      term, firsthand knowledge of the patient's medical and family history.
      Consequently, the general practitioner has a key role in identifying individuals
      with early heart failure. It is essential that the general practitioner is aware
      of the signs and symptoms of early heart failure, can interpret them correctly
      and knows what follow-up tests are necessary to confirm the diagnosis. Guidelines
      are presented here to assist the general practitioner in this task.

PMID- 7649339
TI  - Ergoloids and ischaemic strokes; efficacy and mechanism of action.
AB  - In this double-blind, randomized study the efficacy of the ergoloid compounds, co
      dergocrine mesylate and nicergoline, in the rehabilitation of patients with
      ischaemic stroke was investigated. A group of 30 patients was treated daily with
      60 mg nicergoline, orally, and a second group of 27 patients was given 1.8-6 mg
      co-dergocrine mesylate, orally or intramuscularly, daily (depending on the time
      since the initial ischaemic insult) for 6 months. Outcome measures included:
      motoricity index (limb function); Sandoz Clinical Assessment Geriatric (SCAG)
      scale; psychometric tests to assess functions such as attention, psychomotor
      performance, perception and sensory and short-term memory; conventional and
      computerized electroencephalography; and P300 and reaction time measures. The
      results showed improvements in some aspects such as limb function (P < 0.05),
      SCAG score (P < 0.01) and some electrophysiological parameters (P < 0.01) after
      treatment with both drugs. Though statistically significant most of the changes
      were not large. The efficacy of both drugs was qualitatively similar. The
      quantitative difference in some aspects in favour of nicergoline could be
      attributed to differences in the mechanisms of action of the two drugs, although
      it is also possible that the difference may reflect the dosages used. Nootropic
      drugs may induce a condition that facilitates the effects of cognitive training.

PMID- 7649340
TI  - Astemizole-D causes less sleep impairment than loratadine-D.
AB  - This randomized, double-blind, double-dummy, parallel-group trial was initiated
      to evaluate and compare the tolerability of once-daily astemizole-D capsules (10
      mg astemizole/240 mg pseudoephedrine) and twice-daily loratadine-D tablets (5 mg
      loratadine/120 mg pseudoephedrine), with particular reference to the impact of
      treatment on quality of sleep. A total of 240 healthy volunteers participated in
      this study with a treatment duration of 3 days. Astemizole-D consistently
      produced less sleep impairment than loratadine-D with statistically significant
      differences in favour of astemizole-D reported for night-time waking on days 4
      and 5 (P = 0.004 and P = 0.006, respectively), as well as for night-time
      restlessness on day 4 and the total score for all sleep parameters on day 4 (P <
      0.05). Global evaluations of overall sleep quality at the end of the trial also
      revealed some statistically significant differences in favour of astemizole-D.
      Both drugs were well tolerated and there were no differences in the incidence and
      type of adverse events reported in the two treatment groups. Slight changes in
      heart rate and blood-pressure were observed in both treatment groups, but these
      were small and were not considered to be of clinical significance. In conclusion,
      once-daily astemizole-D is well tolerated and appears to cause less sleep
      impairment than twice-daily loratadine-D.

PMID- 7649341
TI  - Efficacy and tolerability of levodropropizine and dropropizine in children with
      non-productive cough.
AB  - The antitussive efficacy and tolerability of dropropizine and of its enantiomer
      levodropropizine were evaluated in children with non-productive cough; 258 were
      evaluable for tolerability and 254 for efficacy. Patients randomly received
      either 1 mg/kg dropropizine or 2 mg/kg levodropropizine orally, three times daily
      for 3 days. There were statistically significant decreases in the frequency of
      coughing spells and nocturnal awakenings after both levodropropizine and
      dropropizine treatments (P < 0.001). Gastro-intestinal symptoms were mild in the
      two groups; somnolence was twice as frequent in the dropropizine group (10.3% vs
      5.3%) and the difference is clinically relevant, though not statistically
      significant. Levodropropizine is as effective as an antitussive as dropropizine,
      but appears to carry a lower risk of daytime somnolence.

PMID- 7649342
TI  - A new mechanism of serum creatine phosphokinase elevation in strangulated small
      bowel obstruction: an experimental rat model.
AB  - An experimental rat model was used to investigate the mechanisms of serum
      creatine phosphokinase (CPK) elevation in strangulated small bowel obstruction.
      Two models were used: a strangulated ileus model with the bowel lumen and blood
      flow obstructed simultaneously, and a control ileus model with only the bowel
      lumen occluded. The experiments demonstrated that CPK was released into the blood
      when the mesenteric blood flow was restored, and that CPK was released into the
      intestinal lumen in the strangulated ileus model but not the control ileus model.
      CPK activity in the mucosal layer of the strangulated ileus model was
      significantly decreased compared with that in the control ileus model. Purified
      CPK injected into the intestinal lumen was absorbed by the healthy intestine.
      These results suggest a new mechanism of serum CPK elevation in strangulated
      small bowel obstruction in which serum CPK is elevated with a significant
      decrease in mucosal CPK. Strangulated bowel content including mucosal CPK may be
      reabsorbed by the healthy distal intestine when bowel obstruction is incomplete.

PMID- 7649343
TI  - Calcium intakes in a sample of 35,000 Italian schoolchildren.
AB  - The calcium intakes of 35,072 Italian schoolchildren aged 7-10 years were
      investigated as part of a nation-wide survey of nutritional patterns. The Friuli,
      Piedmont, Latium and Sicily regions of Italy were selected as representative of
      the nation's north-south and east-west socio-economic divisions. A food-frequency
      questionnaire was used to assess the nutritional intakes of the whole sample. The
      validity of the food-frequency questionnaire method was assessed in a sub-sample
      of children by traditional methods: 24-h dietary recall and a weighted food
      diary. The data indicate that the mean calcium intakes of girls were below the
      recommended daily intake of 800 mg in all of the regions except Sicily, and that
      the calcium intakes of boys were above the recommended daily intake in all of the
      regions except Friuli. These results suggest that there may be deficiencies in
      the calcium intakes of this age-group in the wider population, particularly in
      girls. Food-frequency questionnaires are potentially valuable as part of a multi
      method approach in large-scale nutritional monitoring.

PMID- 7649344
TI  - Pulmonary endothelial cell modifications after storage in solid-organ
      preservation solutions.
AB  - During lung preservation, the vascular endothelium is probably the first site of
      damage and these lesions are considered the main limiting factor in solid-organ
      preservation. In the present study, the ultrastructural changes in the
      endothelial cells of human pulmonary artery hypothermically stored (at 4 degrees
      C) for 6 and 12 h in Euro-Collins, University of Wisconsin and Ringer-lactate
      solutions were compared. The arteries obtained from three patients who underwent
      pneumonectomy were divided into 20 segments and preserved in the three solutions
      mentioned. The specimens, which were fixed in osmic acid, were examined using
      transmission electron microscopy. Transmission electron microscopy indicated that
      the cells stored in the University of Wisconsin solution either for 6 or 12 h
      were the best preserved, while the most severely damaged cells were those stored
      in Euro-Collins solution, even after just 6 h. The cells stored in Ringer-lactate
      showed an intermediate level of damage. The data from an ultrastructural grading
      scale, which quantified the damage to the cytoplasm, mitochondria and nucleus,
      were in broad agreement with the general transmission electron microscopy
      observations. Analysis of variance of the grading scale data showed that there
      were statistically significant differences between the groups after both 6 and 12
      h storage (P < 0.05).

PMID- 7649345
TI  - Pregnancy by tubal insemination in rabbits using sperm cells capacitated in
      vitro.
AB  - It has been suggested that the mechanical interference involved in inserting a
      tube into the oviduct before ovulation, during tubal insemination, may impair the
      capacity of the tubal fimbriae to pick up ovulated eggs. When fresh sperm cells
      are used, the semen has to be injected into the oviduct before ovulation to allow
      time for sperm capacitation. In the present study in rabbits, sperm cells
      capacitated by pre-incubation in vitro were injected into the oviducts through
      the tubal fimbriae after ovulation. Two of the six rabbits inseminated became
      pregnant and gave birth to one and three offspring, respectively. Injecting
      capacitated sperm cells after ovulation may avoid the potential problems posed by
      mechanical damage of the tubal fimbriae.

PMID- 7649346
TI  - Epidural morphine plus bupivacaine for relief of post-operative pain following
      Harrington rod insertion for correction of idiopathic scoliosis.
AB  - The aim of this study was to assess the efficacy of epidural morphine plus
      bupivacaine for post-operative pain control following Harrington rod insertion.
      In 22 scoliotic patients, studied prospectively, the epidural catheter was
      positioned under direct vision, intra-operatively before wound closure. Post
      operatively, the patients received 2 mg morphine in 4 ml of 0.25% bupivacaine
      through the epidural catheter whenever they complained of pain. The pain score
      was assessed before and after every injection, using the Visual Analogue Pain
      Scale, and side-effects were monitored. All patients had adequate pain relief
      following analgesic administration. The mean (+/- SD) pre-injection pain score
      decreased from 2.5 +/- 0.15 on the first post-operative day to 0.7 +/- 0.2 by the
      fourth day. The side-effects, including nausea, vomiting and pruritus, were
      minimal. It is concluded that morphine, in 0.25% bupivacaine administered through
      an intra-operatively placed epidural catheter, provides a safe and effective post
      operative analgesia in patients undergoing Harrington rod insertion for
      idiopathic scoliosis.

PMID- 7649347
TI  - Glucocorticoid receptor, mineralocorticoid receptors, 11 beta-hydroxysteroid
      dehydrogenase-1 and -2 expression in rat brain and kidney: in situ studies.
AB  - In mammals, 11 beta-hydroxysteroid dehydrogenase (11-HSD) activity allows
      aldosterone occupancy of mineralocorticoid receptors (MR) by inactivating
      endogenous glucocorticoids. The present study examined the distribution of 11
      HSD2, 11-HSD1, glucocorticoid receptor (GR) and MR in kidney and brain. High
      levels of expression of 11-HSD2 were found in renal cortical distal tubules and
      more diffusely expressed in distal tubules of the medulla. No expression of 11
      HSD2 was found on serial sectioning of the brain. 11-HSD1 was expressed in
      proximal tubules of the kidney and throughout the brain. GR mRNA was found
      predominantly in renal proximal tubules and diffusely in brain, while MR mRNA was
      located in the renal distal tubules and also in various brain nuclei. These
      anatomical findings support a functional relationship between 11-HSD1 and GR in
      both brain and kidney, but between 11-HSD2 and MR in kidney only.

PMID- 7649348
TI  - Transforming growth factor beta secretion from primary breast cancer fibroblasts.
AB  - Transforming growth factor beta (TGF-beta) is a hormonally regulated growth
      inhibitor with autocrine and/or paracrine functions in human breast cancer. In
      vivo, enhanced immunohistochemical staining of extracellular TGF-beta 1 has been
      detected around stromal fibroblasts in response to the antiestrogen treatment. We
      have investigated the effects of tamoxifen on the production of TGF-beta by
      primary human breast fibroblast cultures in serum-free medium. Highly variable
      levels of mainly latent TGF-beta 1 were detected in conditioned media from both
      tumor and normal tissue derived fibroblasts. Hydroxy-tamoxifen was shown to
      increase latent TGF-beta 1 secretion in three of the eight tumor tissue-derived
      fibroblast cultures. Such effect of hydroxy-tamoxifen was not observed in
      fibroblast cultures established from normal adjacent breast tissue.

PMID- 7649349
TI  - Complete androgen insensitivity syndrome due to a new frameshift deletion in exon
      4 of the androgen receptor gene: functional analysis of the mutant receptor.
AB  - We studied the androgen receptor gene in a large kindred with complete androgen
      insensitivity syndrome and negative receptor-binding activity, single-strand
      conformation polymorphism (SSCP) analysis and sequencing identified a 13 base
      pair deletion within exon 4. This was responsible for a predictive frameshift in
      the open reading frame and introduction of a premature stop codon at position 783
      instead of 919. The deletion was reproduced in androgen receptor wildtype cDNA
      and transfected into mammalian cells. Western blot showed a smaller androgen
      receptor of 94 kDa for the transfected mutated cDNA instead of 110 kDa. Androgen
      binding assay of the mutated transfected cells assessed the lack of androgen
      binding. Gel retardation assay demonstrated the ability of the mutant to bind
      target DNA; however, the mutant was unable to transactivate a reporter gene.
      Although the role of the partial deletion in the lack of androgen action was
      expected, in vitro analyses highlight the role of the abnormal C-terminal portion
      in the inhibition of the receptor transregulatory activity of the protein causing
      androgen resistance in this family.

PMID- 7649350
TI  - The expression of prostatic acid phosphatase is transcriptionally regulated in
      human prostate carcinoma cells.
AB  - The expression of prostatic acid phosphatase (PAcP) in three human prostate
      carcinoma cell lines including LNCaP, DU 145 and PC-3, was studied to explore its
      potential role as a marker in the progression of prostate cancer. Although
      Southern blot analysis suggested the presence of PAcP gene in all three prostate
      carcinoma cell lines, the Northern blot analysis and the reverse transcriptase
      polymerase chain reaction (RT-PCR) assay showed that PAcP mRNA can be detected
      only in LNCaP cells. As one of the major differences between LNCaP cells and PC-3
      as well as DU 145 cells is the androgen-sensitivity of LNCaP cells, we then
      focused on the influence of PAcP expression by the presence of androgen receptor
      (AR) in human AR cDNA-transfected PC-3 cells and high passages of LNCaP cells.
      The results demonstrated that the transfection of human AR cDNA into PC-3 cells
      did not have any detectable effect on the expression of PAcP. Further, in LNCaP
      cells, while the level of PAcP mRNA diminished upon passage, the AR mRNA level
      remained approximately the same. Together, these data suggested that the
      differential expression of PAcP in different prostate carcinoma cells including
      high passages of LNCaP cells may occur at the transcriptional level and may have
      little linkage to the expression of AR.

PMID- 7649351
TI  - 20-Hydroxyecdysone stimulates RNA polymerase I activity in silkmoth wing
      epidermis by increased synthesis and phosphorylation.
AB  - The activities of RNA polymerases I and II in the wing epidermis of diapausing
      silkmoth pupae increased about tenfold during the first day after administration
      of either 20-hydroxyecdysone (20E) or 20E plus juvenile hormone (Katula et al.,
      1981a). The aim of these studies was to correlate these increases in RNA
      polymerase I and II activities to their amounts in hormone stimulated wing
      epidermis. The enzyme activities were measured by standard procedures while their
      amounts were determined by the application of a modified ELISA with subunit
      specific monoclonal antibodies. Results showed that the increase in the amount of
      RNA polymerase I during the first 24 h accounted for only about 60% of the
      increase in activity. Alkaline phosphatase decreased the activity of the newly
      synthesized enzyme by 40-50%. These results indicate that hormone-stimulation of
      RNA polymerase I activity is due to a combination of synthesis of the enzyme and
      phosphorylation of the enzyme and/or tightly associated factors. RNA polymerases
      II and III determined by differential ELISA using a monoclonal antibody specific
      to a common subunit followed developmental changes similar to those of RNA
      polymerase I. The amounts and activity of the enzymes during the first 48 h were
      similar in wing tissue that followed the second pupal development (20E + juvenile
      hormone) compared to tissue that developed into adult wings (20E).

PMID- 7649352
TI  - Follicle-stimulating hormone transiently induces expression of protooncogene c
      myc in primary Sertoli cell cultures of early pubertal and prepubertal rat.
AB  - The protooncogene c-myc plays an important role in the regulation of cellular
      proliferation and differentiation. To evaluate the possibility that the
      protooncogene c-myc plays some roles in follicle-stimulating hormone (FSH)
      dependent gene regulation of Sertoli cells, the effects of FSH on the expression
      of c-myc has been investigated in primary Sertoli cell cultures. FSH was no
      change to the c-myc mRNA level before 18 h, but transiently increased c-myc mRNA
      levels, with maximal stimulation reached in 18 h. The induction of c-myc was
      dependent on the concentration of FSH. Th c-myc mRNA was also increased after
      treatment with dibutyryl c-AMP and forskolin in primary Sertoli cell cultures.
      FSH-dependent c-myc mRNA levels were superinduced in cells treated for 3 h with
      cycloheximide but it was reduced by actinomycin-D pretreatment. Even in the
      absence of FSH in culture medium c-myc mRNA was clearly detectable in Sertoli
      cells from 8-day-old rats but hardly detectable in cells from 14 and 28 days of
      age. FSH stimulated c-myc mRNA expression in the primary Sertoli cells derived
      from only 8- and 14-day-old rats but had almost no effect in the 28-day-old rats.
      These results suggest that FSH induces c-myc mRNA levels in the primary Sertoli
      cells from prepubertal and early pubertal rats, and then transient expression of
      c-myc may be responsible for some roles in the regulation of FSH-dependent genes
      in Sertoli cells.

PMID- 7649353
TI  - Transforming growth factor-beta receptors on human endometrial cells:
      identification of the type I, II, and III receptors and glycosyl
      phosphatidylinositol anchored TGF-beta binding proteins.
AB  - In the present study, we have characterized the cell surface receptors for
      transforming growth factor-beta (TGF-beta) on monolayer cultures of stromal cells
      prepared from human endometrial biopsies, and on a human endometrial epithelial
      cell line (RL95-2) using affinity cross-link labeling techniques. On the stromal
      cells, five TGF-beta binding proteins were identified. Analysis of the
      sensitivity of these proteins to dithiothreitol and phosphatidylinositol-specific
      phospholipase C, together with results from immunoprecipitations with antibodies
      against the type II and III TGF-beta receptors, confirmed that three of these
      binding proteins correspond to the cloned type I, II, and III TGF-beta receptors.
      The other two binding proteins observed exhibit the characteristics of isoform
      specific GPI-anchored TGF-beta binding proteins. On RL95-2 cells, three TGF-beta
      binding proteins, corresponding to the type I, II, and III TGF-beta receptors,
      were identified. The receptors which we have characterized on endometrial cells
      are responsive to physiological concentrations of TGF-beta as demonstrated by the
      effect of TGF-beta on endometrial cell proliferation. Accordingly, these
      receptors have the potential to respond to the TGF-beta isoforms which have
      recently been detected in the endometrium in an autocrine and/or paracrine
      manner.

PMID- 7649354
TI  - Sex hormones mediate interleukin-1 beta production by human osteoblastic HOBIT
      cells.
AB  - The mechanisms by which the sex hormones achieve their bone-sparing effects
      remains unresolved. Interleukin-1 beta (IL-1 beta) is an autocrine/paracrine
      regulator of bone that may be produced in an estrogen-sensitive manner. The
      regulation of IL-1 beta production by the gonadal steroids was tested in the
      human osteoblastic HOBIT cell model. Dose-dependent 4-8-fold increases (P < 0.05)
      in IL-1 beta mRNA levels followed a 6-48 h treatment with 17 beta-estradiol or
      testosterone. Receptor mediation of these responses was indicated by experiments
      using 17 alpha-estradiol or flutamide. Tumor necrosis factor-alpha (TNF)
      dependent increase IL-1 beta mRNA levels were additive to the effects of the
      steroids. Testosterone and TNF increased IL-1 beta protein release (P < 0.05)
      while 17 beta-estradiol had little effect on release. The bone-sparing effects of
      the gonadal steroids may be accomplished, in part, through their mediation of
      local IL-1 beta production.

PMID- 7649355
TI  - Involvement of protein phosphatases in gonadotropin releasing hormone regulated
      gonadotropin secretion.
AB  - The role of persistent protein phosphorylation upon gonadotropin releasing
      hormone (GnRH) stimulated luteinizing hormone (LH) release was investigated by
      the use of the selective inhibitors of protein phosphatase type 1 (PP1) and 2A
      (PP2A), okadaic acid (OA) and calyculin A. Pre-incubation of cultured rat
      pituitary cells with OA (24 h) or calyculin A (30 min) resulted in inhibition of
      GnRH-stimulated LH release with significant inhibition being detected at 10 nM
      and 30 nM for OA and calyculin A, respectively. The inactive OA analog norokadone
      and the protein tyrosine phosphatase inhibitor vanadyl hydroperoxide had no
      significant effect on GnRH-induced LH release. The stimulatory effects of the
      protein kinase C (PKC) activator 12-O-tetradecanoylphorbol 13-acetate (TPA, 50
      ng/ml) or the Ca2+ ionophore, ionomycin (1 micron), upon LH release were also
      abolished by pretreatment with OA (10-20 nM) or calyculin A (30 nM). Stimulation
      of LH release by high K+ (28 mM) or residual LH release stimulated by GnRH in
      Ca(2+)-free medium were also blocked by OA. These observations indicate that
      protein dephosphorylation is involved positively in GnRH-stimulated LH release.
      The site of action of the protein phosphatases PP1 and PP2A is most likely
      downstream to Ca2+ elevation and PKC activation by GnRH.

PMID- 7649356
TI  - Oestrogen-induced genes, pLIV-1 and pS2, respond divergently to other steroid
      hormones in MCF-7 cells.
AB  - The level of oestrogen-responsive gene expression in breast tumours has been
      proposed as a predictor of the response of the tumour to endocrine (anti
      oestrogen) therapy. We demonstrate that different oestrogen-responsive genes may
      differ in their responses to other hormones. pLIV-1 and pS2 are two oestrogen
      regulated genes that are expressed in the MCF-7 human breast cancer cell line. We
      show that pLIV-1 mRNA, but not pS2 mRNA, is also induced, to a lesser extent, by
      progesterone, 5 alpha-dihydrotestosterone and dexamethasone. For pLIV-1,
      combinations of these hormones with oestradiol and with the pure anti-oestrogen,
      ICI 164384, indicate that the mechanism of its response to these other steroid
      hormones is clearly separable from its response to oestrogen. Such behaviour in
      breast tumours in vivo could explain the lack of absolute correlation between
      marker gene expression and anti-oestrogen sensitivity and between the expression
      of individual marker genes.

PMID- 7649357
TI  - Occurrence of cytochrome P450c17 mRNA and dehydroepiandrosterone biosynthesis in
      the rat gastrointestinal tract.
AB  - We have investigated 17 alpha-hydroxylase and C17,20-lyase activities and the
      presence of cytochrome P450c17 mRNA in the esophagus, stomach, duodenum, and
      colon of adult rats of both sexes. All tissues converted [4-14C]pregnenolone
      mainly to dehydroepiandrosterone (DHEA) through the 5-ene-3 beta-hydroxysteroid
      route as opposed to the 4-ene-3-ketosteroid pathway in a control testicular
      incubate. Synthesis of dehydroepiandrosterone was particularly high in the
      duodenum and was found to be lower in the stomach, colon and esophagus, in
      decreasing order. 20 alpha-Hydroxypregnenolone and progesterone were also formed
      primarily by the esophagus and colon, respectively. P450c17 mRNA was demonstrated
      by ribonuclease protection assay in the stomach and duodenum, but not in
      esophagus and colon. However, a 335 bp-long cDNA fragment, whose sequence
      corresponded to that of rat P450c17 cDNA, was amplified by reverse transcription
      (RT) and polymerase chain reaction (PCR) from the poly(A)+ RNAs of all four
      tissues. This result was further confirmed by Southern blotting using a 794-bp
      testicular probe. The complete sequence of P450c17 cDNA in the stomach and
      duodenum was identical to that reported for rat testis P450c17 cDNA. No
      amplification and no positive signal in Southern blotting were observed with the
      total RNAs from adult male adrenal and spleen, which were taken as negative
      controls since they had been previously found unable to form androgens from
      pregnenolone. Although the levels of transcription in gonads, duodenum and
      stomach were found to be equivalent, as indicated by the RNase protection assay
      and semiquantitative RT-PCR assay, P450c17 enzyme activity was much higher in the
      testis, pointing at a possible dissimilarity in the respective rates of mRNA
      translation. Thus, P450c17 is differentially expressed in the rat
      gastrointestinal tract, where it leads to the synthesis of the sex steroid
      precursor DHEA, especially in the duodenum and stomach.

PMID- 7649358
TI  - A single amino acid exchange abolishes dimerization of the androgen receptor and
      causes Reifenstein syndrome.
AB  - A single exchange of an alanine to a threonine at amino acid position 596 in the
      androgen receptor has been identified as an inheritable trait in patients with
      Reifenstein syndrome. This exchange is a result of a germ line mutation in the
      genomic DNA sequences that make up the D-loop of the receptor. The D-loop and
      sequences in the hormone binding domain together provide the interacting surfaces
      for receptor dimer formation and subsequent binding to DNA. Here we show that the
      single amino acid exchange abolishes dimerization of the receptor. With this
      finding we demonstrate that the destruction of dimerization of the androgen
      receptor is one of the causes of Reifenstein syndrome.

PMID- 7649359
TI  - Hydrogen peroxide degradation and glutathione peroxidase activity in cultures of
      thyroid cells.
AB  - The degradation rate of H2O2, added to the incubation medium, and glutathione
      (GSH) peroxidase activity were measured in cultures of FRTL-5 cells and porcine
      thyroid cells. The H2O2 degradation rate increased proportionally to the H2O2
      concentration and was in FRTL-5 cells, cultured with TSH, approximately 50
      nmol/min and mg DNA at 0.01 mM H2O2 and approximately 3 x 10(4) nmol/min and mg
      DNA at 10 mM H2O2. The GSH peroxidase activity in the same cells was equivalent
      to an H2O2 degradation of approximately 400 nmol/min and mg DNA. The involvement
      of enzymes in H2O2 degradation was studied by inhibiting catalase with
      aminotriazole (ATZ) and reducing GSH peroxidase by omitting glucose in the
      incubation medium. At 0.1 mM H2O2, ATZ or glucose omission alone did not
      measurably reduce H2O2 degradation but did so when combined. At 10 mM H2O2 ATZ
      caused a clear inhibition whereas glucose omission had no additive effect. These
      observations indicate that GSH peroxidase was involved in H2O2 degradation only
      at low H2O2 concentrations. The GSH peroxidase activity decreased by reduction of
      the selenite supply and increased after replenishment. The recovery of the enzyme
      activity required the presence of TSH in FRTL-5 cells but not in porcine
      thyrocytes.

PMID- 7649360
TI  - Integrin alpha v subunit is expressed on mesodermal cell surfaces during
      amphibian gastrulation.
AB  - Mesodermal cell migration during amphibian gastrulation is dependent on cellular
      interactions with fibronectin. One mechanism whereby cells bind fibronectin is
      through alpha v-containing integrin heterodimers. In order to investigate the
      role of alpha v in amphibian gastrulation, we have cloned the Pleurodeles
      homologue of the integrin alpha v subunit using homology PCR. The deduced amino
      acid sequence is 73 and 74% identical with the human and chick homologues,
      respectively. The 4.8-kb mRNA is expressed during oogenesis and persists
      throughout development. Messenger RNA and protein are widely expressed in oocytes
      and embryos while cell surface expression is spatially regulated. The protein
      first appears on the plasma membrane of fully grown oocytes. Fertilization
      results in the progressive loss of alpha v membrane localization. Before and
      during gastrulation, the integrin alpha v subunit is expressed on the surface of
      mesodermal cells. These data show that alpha v expression is developmentally
      regulated by a post-translational mechanism which correlates with the onset of
      mesodermal cell migration at gastrulation.

PMID- 7649361
TI  - Modifications of gene expression in myotonic murine skeletal muscle are
      associated with abnormal expression of myogenic regulatory factors.
AB  - The mouse mutants ADR ("arrested development of righting") and the allelic CRP
      ("cramp") are characterized by a myotonic phenotype resulting from a dysfunction
      of the skeletal muscle chloride channel which leads to myotonic trains of actions
      potentials in response to stimuli. Compared to normal mouse muscle, numerous
      biochemical modifications have been found in the ADR muscle, and changes are
      observed in the expression of certain isoforms of contractile proteins. We have
      therefore measured the levels of the mRNA transcripts encoding the myosin heavy
      chain isoforms (MyHC) in both mutants. Transcripts for the myogenic regulatory
      factors were also studied since they are known to play a role in the induction of
      muscle-specific gene transcription, and their own expression is modified by
      different electrical activity patterns. In both mutants, the mRNA encoding the
      IIB MyHC was considerably decreased. In contrast, the mRNAs for the IIA, IIX, and
      beta/slow MyHCs were increased. The mRNA for the neonatal MyHC mRNA was not
      detectable, and therefore fiber regeneration does not appear to play a role in
      these phenomena. Among the myogenic regulatory factors, herculin is the most
      abundant in adult muscle; however, herculin mRNA undergoes a large decrease in
      myotonic muscle which does not seem to be related to the changing fiber type. The
      levels of MyoD and myogenin mRNAs are also modified with the former decreasing
      and the latter increasing. Qualitatively similar changes are seen in the ADR and
      CRP mutants; however, they are generally less pronounced in CRP. These
      observations suggest that specific myogenic factors may be linked to the
      expression of individual MyHC genes and that abnormal expression of some of the
      factors may be associated with myotonic muscle pathology.

PMID- 7649362
TI  - Molecular analysis and developmental expression of the focal adhesion kinase
      pp125FAK in Xenopus laevis.
AB  - Integrin-mediated cellular adhesion to components of the extracellular matrix
      (ECM) is important in a number of morphogenetic events that occur during
      vertebrate embryogenesis. Recent studies suggest that the focal adhesion kinase
      pp125FAK is involved in the regulation of integrin-dependent signaling processes
      triggered by cell adhesion to the ECM. We report the cDNA cloning and sequence
      analysis of the Xenopus homolog of pp125FAK. We also describe temporal and
      spatial patterns of FAK expression during early development. Xenopus FAK shares
      greater than 90% identity with its avian and mammalian homologs. FAK mRNA and
      protein are present in the fertilized egg and in cleavage stage embryos. During
      gastrulation, FAK protein expression increases significantly and is detected in
      mesoderm, marginal zone ectoderm, and cells of the blastocoel roof. Later in
      development, FAK is prominently expressed at intersomitic junctions, in the
      brain, and in several cranial nerves. Phosphotyrosyl-FAK is first detected during
      gastrulation, suggesting that the phosphorylation of FAK on tyrosine is
      developmentally regulated. These data indicate that FAK is likely to participate
      in a variety of integrin-ECM-dependent signaling events during morphogenesis.

PMID- 7649363
TI  - Skin abnormalities in mice transgenic for plasminogen activator inhibitor 1:
      implications for the regulation of desquamation and follicular neogenesis by
      plasminogen activator enzymes.
AB  - Plasminogen activator enzymes have been implicated in the regulation of growth,
      migration, and differentiation which occur continually in normal epidermis and
      cyclically in the hair follicle. To elucidate further the importance of
      plasminogen activation in epidermal physiology, studies were conducted using mice
      transgenic for human plasminogen activator inhibitor 1 (PAI-1). The epidermis of
      the newborn (4-7 days) transgenic mice was flaky and showed delayed hair growth
      compared to that of their control littermates. Histologic analyses revealed a
      greatly thickened stratum corneum in the transgenics. By 2 weeks after birth, no
      differences in epidermal morphology were apparent between transgenic and control
      littermates. Using in situ hybridization, immunocytochemistry, and in situ
      reverse zymography techniques, epidermal PAI-1 expression was correlated
      temporally with the aberrant epidermal morphology. These data implicate
      plasminogen activator activity in the regulation of epidermal shedding and
      follicular neogenesis.

PMID- 7649364
TI  - Early stages of notochord and floor plate development in the chick embryo defined
      by normal and induced expression of HNF-3 beta.
AB  - We have cloned a cDNA encoding the chick HNF-3 beta gene and have used RNA and
      antibody probes that detect HNF-3 beta to monitor the normal and induced
      expression of the gene in early embryos. HNF-3 beta expressed in Koller's sickle,
      at the onset of primitive streak formation, and later in Hensen's node. At neural
      plate and neural tube stages, HNF-3 beta is expressed transiently in the
      notochord and is then expressed by floor plate cells. Prospective floor plate
      cells that are located in the epiblast immediately anterior to Hensen's node
      prior to its regression do not express HNF-3 beta, providing evidence that floor
      plate fate is normally determined only after these cells populate the midline of
      the neural plate and overlie the notochord. Removal of the notochord in vivo
      prevents floor plate development and in this condition HNF-3 beta is not
      expressed by cells at the ventral midline of the neural tube. Notochord grafts
      induce ectopic floor plate development and ectopic neural expression of HNF-3
      beta. In vitro, neural plate explants are induced to express HNF-3 beta by
      notochord cells in a contact-dependent but cycloheximide-resistant manner,
      providing evidence that expression of HNF-3 beta is a direct response of neural
      plate cells to notochord-derived inducing signals.

PMID- 7649365
TI  - Follicle cell calmodulin in Blattella germanica: transcript accumulation during
      vitellogenesis is regulated by juvenile hormone.
AB  - There is abundant calmodulin (CaM) in the oocytes and eggs of B. germanica.
      Whether oocytes accumulate CaM for immediate use or use at a later stage in their
      development is still unknown. We show that isolated follicle cells accumulate
      more CaM transcripts per unit RNA than any other control tissue. CaM transcript
      increases exponentially 4800-fold in follicles during the 96-hr vitellogenic
      period in the absence of cell division. This includes a 32-fold increase in total
      follicle RNA during the period and an 150-fold increase in relative titer of the
      CaM transcript. In comparison, levels of actin transcripts increase exponentially
      1200-fold during the same developmental period. On the other hand fat body tissue
      shows little relative increase of CaM transcripts despite a 4-fold increase in
      total RNA over the 4-day developmental period. Both the CaM and actin transcripts
      are more highly concentrated in the Day 4 follicle cell layer, being found in 84-
      and 33-fold greater titer, respectively, than in fat body RNA. Deprivation of
      juvenile hormone (JH), by head ligation, not only causes atresia of the
      follicles, but also reduces accumulated CaM transcripts. Reestablishing JH titer
      by injection allows a selected population of follicles to develop to full size
      and also reinstates CaM transcript levels above that of unligated controls within
      24 hr.

PMID- 7649366
TI  - Slow and fast muscle fibers are preferentially derived from myoblasts migrating
      into the chick limb bud at different developmental times.
AB  - Avian limb myoblasts originate from somites and migrate into the periphery during
      limb bud formation. It is not known how these precursors become arranged into a
      stereotyped pattern of muscles and primary fiber types. We used in vivo surgical
      transplantation and anatomical analyses of thigh muscle patterns to ask whether
      myoblasts migrating into the limb bud at different developmental times adopt
      different fates. When myoblast migration was interrupted by transplanting limb
      bud tissue to the coelomic cavity of a host embryo early in the migratory period
      (stages 16-early 17), few thigh muscles were found at stages 30-33. Primordia
      that were present corresponded to muscles that normally contain a majority of
      slow myotubes. In limbs transplanted slightly later (stages late 17-18), the only
      missing muscles were those that normally contain the highest numbers of fast
      myotubes. Parallel results were obtained in chimeric limbs made by transplanting
      a quail limb bud to a chick host at different times during the migratory period,
      an experimental situation in which the limbs were not depleted of muscle
      precursors or nerves. These findings suggest that the earliest myoblast migrants
      give rise mainly to slow primary myotubes, the later migrants to fast myotubes.
      To determine whether the early limb bud environment defines the fate of migrating
      myoblasts, we assessed fiber type patterns in limbs that developed from young
      limb bud tissue (stages 15-early 16) transplanted to older hosts (stage 17). A
      significant depletion of slow myosin-positive profiles was found within slow
      muscles. Fast muscles were generally normal in size. These results provide in
      vivo evidence that limb myoblast diversity arises prior to the entry of myoblasts
      into the limb. We suggest that there is a gradual change in the proportions of
      myoblasts capable of forming slow and fast fiber types, a change which may begin
      in the somites or early in the migratory period.

PMID- 7649367
TI  - Expression of the Drosophila gooseberry locus defines a subset of neuroblast
      lineages in the central nervous system.
AB  - The development of the central nervous system is known to require lineage
      specific factors that are expressed in neuroblasts and their descendants, as well
      as molecules involved in cell-cell signaling mechanisms. The transcription
      factors encoded by the gooseberry locus appear to be required for the proper
      specification of neuroblasts and their lineages. To examine whether gooseberry
      expression is lineage-specific, we have utilized the FLP recombinase of yeast to
      positively mark cell lineages throughout Drosophila development. In this system,
      the actin5C promoter and the lacZ gene are separated by a polyadenylation signal
      flanked by two direct repeat FRTs. A heat shock is used to induce a pulse of FLP
      recombinase which catalyzes a site-specific recombination event between the FRT
      sites. The resulting excision of the polyadenylation site allows expression of
      lacZ from the actin5C promoter. The descendants of a cell which has undergone a
      recombination event are now positively marked, enabling us to compare cell
      lineages with the pattern of gooseberry gene expression. We find that the
      expression of the gooseberry locus is lineage-specific, suggesting that
      gooseberry may function as a selector gene in the patterning of the Drosophila
      central nervous system.

PMID- 7649368
TI  - Calmodulin-dependent protein kinase II is activated transiently in ethanol
      stimulated mouse oocytes.
AB  - The activity of calmodulin-dependent protein kinase II (CaMKII) was measured in
      mouse oocytes arrested in metaphase II and following their activation
      parthenogenetically. In metaphase II-arrested oocytes CaMKII was inactive.
      However, following the exposure of oocytes to ethanol, the kinase was highly
      active, returning to baseline activity within 15 min of their removal from
      ethanol. The increase in kinase activity was similar in recently ovulated and
      older oocytes despite an age-dependent difference in their ability to progress to
      interphase. Moreover, the microtubule-depolymerizing drug nocodazole, which
      blocks the exit from M phase in mouse oocytes, had no effect on CaMKII
      activation. These results illustrate clearly that CaMKII is activated in mouse
      oocytes in response to a rise in intracellular calcium and is acting upstream of
      the microtubule-dependent cyclin destruction machinery.

PMID- 7649369
TI  - Pole cell migration through the gut wall of the Drosophila embryo: analysis of
      cell interactions.
AB  - Early in development the precursors of germ cells in Drosophila migrate at the
      posterior pole of the embryo and translocate to the bottom of the developing
      posterior midgut primordium. At the end of germ band elongation the pole cells
      cross the gut wall to enter in association with the gonadal mesoderm. We used
      laser scanning confocal microscopy on whole-mount Rh-phalloidin-stained embryos
      and transmission electron microscopy to investigate how pole cells cross the
      epithelial wall of the posterior midgut primordium. Our results suggest that pole
      cells leave the midgut sac by traveling through the intercellular spaces of the
      epithelium. During this process the epithelial cells at the bottom of the
      posterior midgut primordium are greatly deformed, but their junctional complexes
      do not completely release, avoiding breaks in the epithelial wall.

PMID- 7649370
TI  - Three regions of the 32-cell embryo of Xenopus laevis essential for formation of
      a complete tadpole.
AB  - To examine the conditions of cell composition necessary for formation of a
      complete tadpole, defect embryos of 35 series were prepared by removing
      particular cells from 16- and 32-cell embryos of Xenopus laevis. These defect
      embryos were cultured and their development was examined. Formation of a complete
      tadpole did not require a special cell in the embryo, but did require cell
      combinations as follows: (1) A set of dorsal cells with a sufficient capacity to
      initiate axial structures. (2) Dorsal-most and ventral-most cells or dorsal-most
      and ventrolateral cells of the vegetal hemisphere. (3) The animal-most and
      vegetal-most tiers and either one of the upper-equatorial or the under-equatorial
      tiers. On the basis of these conditions, the minimal set of cells required for
      formation of a complete tadpole was determined. The minimal set included one
      dorsovegetal, two ventrovegetal, and eight animal cells in a lateral hemisphere
      of the 32-cell embryo. Forty percent of defect embryos with this minimal set
      developed into about quarter-sized but otherwise normal tadpoles. These tadpoles
      are the smallest complete tadpoles which have been experimentally obtained. The
      results of these experiments suggest that formation of a complete tadpole
      requires at the least cells in three different regions of the 32-cell embryo,
      that is, the animal, dorsovegetal, and ventrovegetal regions. The mechanism of
      pattern formation at the blastula stage is discussed, in consideration of the
      "three signal model" of mesoderm formation.

PMID- 7649371
TI  - Modulated expression of type X collagen in Meckel's cartilage with different
      developmental fates.
AB  - Mammalian Meckel's cartilage undergoes regionally diverse histodifferentiation:
      the caudal end of Meckel's cartilage extends to the developing ear and gives rise
      to malleus and incus through endochondral ossification while its major distal
      region differentiates into sphenomandibular ligament and the anterior ligament of
      the malleus tympanic plate through fibrous transformation. Since the entire
      Meckel's cartilage develops up to chondrocyte hypertrophy, the regional
      extracellular matrix components in the hypertrophic Meckel's cartilage may differ
      in association with the diverse developmental fates. In this project, the
      expressions of cartilage collagens were investigated in developing rat Meckel's
      cartilage and particular interest was given to type X collagen. A cDNA, HP114,
      encoding the NC1 domain of rat alpha 1(X) collagen was cloned, and a synthetic
      peptide based on the sequence deduced from HP114 was used to generate a
      monospecific antibody. In situ hybridization of newborn rat condylar and angular
      cartilages undergoing endochondral ossification showed restricted labeling with
      the alpha 1(X) collagen probe in the hypertrophic chondrocyte layer. In contrast,
      the alpha 1(X) collagen probe totally failed to label the major distal portion of
      Meckel's cartilage even in the hypertrophic cartilage zone. Immunohistochemistry
      using the anti-type X collagen monospecific antibody consistently failed to
      recognize the epitope in the corresponding portion of Meckel's cartilage
      throughout the experimental periods of gestational Day 17, newborn, and Postnatal
      Day 7, while the strictly localized positive staining was found in the posterior
      part of Meckel's cartilage which gave rise to malleus and incus. Since major
      cartilage collagens type II and type IX were found to be present throughout
      Meckel's cartilage, we postulate that the regulatory molecular mechanism of type
      X collagen expression may be closely associated with the developmental fates of
      fibrous transformation and endochondral ossification in mammalian Meckel's
      cartilage.

PMID- 7649372
TI  - A gut-to-pharynx/tail switch in embryonic expression of the Caenorhabditis
      elegans ges-1 gene centers on two GATA sequences.
AB  - The Caenorhabditis elegans ges-1 gene (gut esterase No. 1) is expressed only in
      the intestinal lineage, beginning when the developing gut has only four to eight
      cells. We analyze the sequence requirements for this tissue-specific gene
      regulation by injecting deleted/mutated constructs of the ges-1 gene into a
      viable ges-1 (null) strain of worms and assaying heritably transformed embryos by
      esterase histochemistry. Many deletion constructs accurately reconstitute the
      wildtype gut-specific ges-1 expression. However, deletions in the neighborhood of
      1100 bp upstream of the ges-1 ATG abolish ges-1 expression in the developing gut,
      while at the same time activating ges-1 expression in cells of the pharynx/tail
      that appear to belong to the sister lineage of the gut. Deletions of a 36-bp DNA
      region containing two tandem WGATAR sequences are sufficient to cause this gut-to
      pharynx/tail switch in expression pattern. Deletion of either one of the WGATAR
      sites or deletion of an adjoining downstream region directs ges-1 expression only
      in a restricted set of cells of the anterior gut. The ges-1 GATA region acts like
      a gut-specific enhancer in that: (i) it restores ges-1 gut expression when
      reinserted elsewhere into the GATA-deleted ges-1 gene; and (ii) multiple copies
      direct gut expression of an hsp16-lacZ reporter gene. The ges-1 GATA-region also
      acts as the site of the pharynx/tail repression in that reinsertion elsewhere
      into the GATA-deleted ges-1 construct causes repression of ges-1 in the
      pharynx/tail. However, multiple copies of the GATA region are not able to repress
      the heat-induced expression of an hsp16-lacZ reporter gene, suggesting that the
      pharynx/tail repression mechanism is specific to the ges-1 environment. Finally,
      mutation rather than deletion of the individual GATA sequences suggests that gut
      activation and pharynx/tail repression may be due to separate factors. We present
      a molecular model that summarizes these results. The ges-1 control circuitry
      appears surprisingly complex for what might have been expected to be the simplest
      possible example of a nonessential gene expressed early in a clonal embryonic
      lineage.

PMID- 7649373
TI  - Efficient cloning of cDNAs of retinoic acid-responsive genes in P19 embryonal
      carcinoma cells and characterization of a novel mouse gene, Stra1 (mouse LERK
      2/Eplg2).
AB  - Pluripotent mouse P19 embryonal carcinoma (EC) cells have been extensively used
      as a developmental model system because they can differentiate in the presence of
      retinoic acid (RA) into derivatives of all three germ layers depending on RA
      dosage and culture conditions. The expression of several genes has been shown to
      be induced in RA-treated P19 EC cells and, interestingly, some of these genes may
      play important roles during mouse embryogenesis. In view of the increasing
      evidence that RA is a crucial signaling molecule during vertebrate development,
      we have initiated a study aimed at the systematic isolation of genes whose
      expression is induced in P19 cells at various times after exposure to RA. We
      describe here an efficient differential subtractive hybridization cloning
      strategy which was used to identify additional RA-responsive genes in P19 cells.
      Fifty different cDNA fragments corresponding to RA-induced genes were isolated.
      Ten cDNAs represent known genes, 4 of which have already been described as RA
      inducible, while the remaining 40 correspond to novel genes. Many of these cDNA
      sequences represent low-abundance mRNAs. Kinetic analysis of mRNA accumulation
      following RA treatment allowed us to characterize four classes of RA-responsive
      genes. We also report the sequence and expression pattern in mouse embryos and
      adult tissues of one of these novel RA-inducible genes, Stra1, and show that it
      corresponds to the mouse ligand for the Cek5 receptor protein-tyrosine kinase.

PMID- 7649374
TI  - Three-dimensional localization of wild-type and myosin II mutant cells during
      morphogenesis of Dictyostelium.
AB  - Dictyostelium amoebae that lack myosin II (mhcA-) are unable to undergo
      morphogenesis. The cells aggregate slowly to form hemispherical mounds, but the
      mounds never extend a tip upward. Expression of developmentally regulated genes
      appears normal in the absence of morphogenesis. When mixed with an excess of wild
      type cells, some mutant cells form differentiated spores; however, rescue is
      extremely inefficient (Knecht and Loomis, 1988). In order to assess how
      morphogenesis is normally accomplished and why mutants lacking myosin II cannot
      develop, a new method has been developed that allows individual amoebae to be
      localized and tracked at high resolution within the multicellular organism during
      development. Amoebae are labeled with a fluorescent dye at the beginning of
      starvation, mixed with an excess of unlabeled cells, and allowed to develop. The
      three-dimensional position of labeled cells in the multicellular organism is then
      determined using a laser scanning confocal microscope. Using this methodology, we
      have shown that labeled wild-type cells are randomly distributed throughout the
      organism and complete development normally. When labeled mhcA- mutant cells are
      mixed with a 20-fold excess of wild-type cells, they are non-randomly localized
      even at the earliest stages of development. Mutant cells in aggregation streams
      are found primarily at the edges of the streams and many cells never become part
      of the streams or are left behind as the wild-type cells complete aggregation.
      Those that are incorporated into the aggregate are found at the edge and base,
      the backs of slugs and the base of the fruiting bodies. A few mutant cells can be
      found in the sorus, where they presumably become spores. The segregation of mhcA-
      mutant cells to the outside of the wild-type aggregation streams argues that the
      mutant cells are unable to penetrate a mass of adhered, wild-type cells. We
      hypothesize that mutant cells lacking cortical integrity are unable to generate
      sufficient protrusive force to break the adhesion of wild-type cells to each
      other. This would make the mutants incapable of moving through a mass of cells
      (either mutant or wild type) or of changing shape when adhered to other cells. We
      propose that mutants lacking myosin II are unable to accomplish morphogenesis
      because they cannot move correctly in a three-dimensional mass of adhered cells.

PMID- 7649375
TI  - Phosphorylation and localization of replication protein A during oogenesis and
      early embryogenesis of Drosophila melanogaster.
AB  - The phosphorylation and localization of Drosophila melanogaster Replication
      Protein A (DRP-A) was examined during oogenesis and in single embryos during the
      syncytial nuclear divisions of embryogenesis. DRP-A from ovaries was separated by
      two-dimensional electrophoresis into multiple phosphorylated species that include
      a previously unresolved form of RP-A. These forms are developmentally regulated
      with a major phosphorylated form appearing at stage 11 of oogenesis and
      persisting into mature eggs. Actively cycling early embryos were examined to
      investigate DNA replication in the absence of repair synthesis due to
      perturbation by drugs or mutation. An oscillation of the two major forms of DPR-A
      was observed over multiple cell cycles. The phosphorylated form was most abundant
      at mitosis and the nonphosphorylated form at interphase. In contrast to other
      systems where a phosphorylated form of RP-A has been correlated with S phase,
      only the nonphosphorylated form of Drosophila RP-A is observed in early
      Drosophila embryos during DNA replication. Consistent with this role in DNA
      metabolism, DRP-A was localized to the nucleus. Subsequently at mitosis, DRP-A
      becomes delocalized. Strikingly, in ovaries a relatively large amount of DRP-A
      was observed during the early mitotic stages of oogenesis.

PMID- 7649376
TI  - Effects of basic fibroblast growth factor on proliferation, the expression of
      osteonectin (SPARC) and alkaline phosphatase, and calcification in cultures of
      human pulp cells.
AB  - Basic fibroblast growth factor (bFGF) may be involved in the development and
      repair of dentine and pulp because bFGF, its related peptides, and FGF receptors
      are expressed in dental mesenchymal cells. In this study, we examined the effects
      of bFGF on DNA synthesis, osteonectin/SPARC levels, alkaline phosphatase (ALPase)
      activity, their mRNA levels, and calcium levels in cultures of human pulp cells.
      Pulp cells were isolated from three healthy upper wisdom teeth of three patients
      and maintained separately. These cells produced SPARC, ALPase, and calcified
      nodules and there was a close correlation between the SPARC-synthetic activity of
      the cell lines and their levels of ALPase and calcification. The levels of SPARC,
      ALPase and calcium deposits in the three pulp cell cultures were 10-250 times
      those of human foreskin fibroblasts. Western blots showed that the pulp cells
      produced 38-kDa SPARC. Northern blots showed that the pulp cells expressed flg
      (FGF receptor type 1) transcripts throughout all culture stages, irrespective of
      the presence or absence of bFGF. The addition of bFGF to the pulp cultures
      suppressed the increases in ALPase activity, SPARC synthesis, and their mRNA
      levels, although it increased the incorporation of [3H]thymidine into DNA > 10
      fold. The effects of bFGF on ALPase activity and SPARC synthesis were reversible.
      Furthermore, bFGF abolished the calcification of the extracellular matrix; the
      calcium content of bFGF-free cultures. These findings suggest that bFGF is a
      potent mitogen for human pulp cells and that it inhibits the expression of the
      odontoblast phenotype by the cells at least partly at pretranslational levels.

PMID- 7649377
TI  - Stage-specific regulation of murine Hsp68 gene promoter in preimplantation mouse
      embryos.
AB  - In early mouse embryos, the major inducible heat shock gene, hsp68, is
      spontaneously and transiently activated at the two-cell stage and becomes heat
      inducible around blastocyst stage. We have probed mouse embryo's ability to
      activate the promoter of this gene during preimplantation development by
      expression analysis of DNA constructs containing a reporter lacZ gene driven by
      hsp68 (hsp70A1) 5'-regulatory sequences of various length: (i) a full-length
      promoter (construct phsplacZ); (ii) a heat shock element (HSE)-deleted promoter
      (p delta 1hsplacZ); and (iii) a minimal, proximal promoter (p delta 2hsplac Z).
      When analyzed in transfected L-cells, phsplacZ was heat-inducible, while neither
      p delta 1hsplacZ nor p delta 2hsplacZ was. Developmental activity of the full
      length construct was first analyzed after genome integration in transgenic
      embryos and found to follow endogenous hsp68 expression in terms of spontaneous
      activation at the 2-cell stage, down-regulation at the 4-cell stage, and
      acquisition of heat inducibility at the 16/32-cell stage. In transient expression
      experiments, injected phsplacZ, p delta 1hsplacZ, and p delta 2hsplacZ were
      expressed at similar levels by 2-cell embryos, independently of construct
      topology and injection stage. At the 4-cell stage, however, phsplacZ and p delta
      1hsplacZ were expressed at similar levels, while p delta 2hsplacZ was inactive.
      Only phsplacZ became heat-inducible in late morulas. We conclude that in early
      mouse embryos, developmental activity of episomic hsp68 promoter depends on
      proximal sequences at the 2-cell stage and on putative enhancer sequences at the
      4-cell stage, while HSEs appear dispensable during early cleavage.

PMID- 7649378
TI  - Expression of nicotinic acetylcholine receptors and subunit mRNA transcripts in
      cultures of neural crest cells.
AB  - The expression of neuronal phenotypic characteristics by neural crest-derived
      neurons is dependent upon both environmental cues and intrinsic properties.
      Neuronal nicotinic acetylcholine receptors (nAChRs) are expressed by most neural
      crest-derived peripheral neurons; nevertheless, the factors that influence and
      modulate the early expression of nAChRs on neuronal precursor cells are unknown.
      We used RT-PCR to analyze the temporal sequence of the appearance of transcripts
      encoding alpha 3, alpha 5, alpha 7, beta 2, and beta 4 nAChR subunits in cultures
      of quail neural crest cells. At 2 days in culture, mRNA encoding each of these
      nAChR subunits was detectable and, except for alpha 7, remained so through 12
      days. The appearance of NAPA 73 immunoreactivity during neural crest cell
      migration suggested that some cells express neuronal characteristics early in
      development and that the expression of nAChR subunits may be cell autonomous for
      some neural crest-derived cells. Between 8 and 10 days in culture, a 2.0-kb
      transcript encoding alpha 3 subunit appears in addition to the expected 3.5-kb
      transcript that is present at 8 days. nAChR protein was detected
      immunocytochemically at 7 days and was observed in immunoblots by 9 days. Whole
      cell patch clamp recordings demonstrated that functional nAChRs develop
      concurrently in a subset of neural crest-derived neurons. In addition, both
      neuronal and nonneuronal cells showed inward and delayed outward currents in
      response to step depolarization. The appearance of functional nAChRs on neural
      crest-derived cells, in vitro, occurs independently of innervation and of the
      components in growth medium. The data suggest that neural crest-derived cells
      express transcripts encoding nAChR subunits, possibly as an intrinsic property of
      some peripheral neurons, early in development.

PMID- 7649379
TI  - Time-lapse confocal imaging of calcium dynamics in starfish embryos.
AB  - During fertilization and cleavage, embryos undergo transient rises in their
      intracellular free calcium levels that are postulated to provide essential
      signals enabling normal development to proceed. In order to analyze the
      spatiotemporal patterns and possible biological significance of these calcium
      transients, time-lapse confocal microscopy was used to monitor starfish embryos
      during normal development and following experimental manipulations that disrupted
      cleavage and/or the release of calcium ions from internal stores in the embryo.
      For such analyses, oocytes were co-injected with dextran-conjugated forms of the
      calcium-sensitive fluorochrome calcium green (CG) and the calcium-insensitive dye
      rhodamine (Rh) for dual-channel confocal ratioing. Based on CG/Rh ratioed images
      obtained every 15 sec for the first few hours of development, no prominent
      calcium spikes were typically evident at the onset of the first cell cycle as
      hormone-treated oocytes resumed maturation and underwent germinal vesicle
      breakdown (GVBD). Subsequently, fertilizations of post-GVBD oocytes caused a
      single prolonged calcium wave that reached relatively uniform amplitudes
      throughout the ooplasm. Within 90 min after fertilization, most starfish zygotes
      began to display clusters of repetitive calcium oscillations that typically-but
      not invariably-preceded nuclear envelope breakdown, anaphase onset, and the
      formation of the first cleavage furrow. Rapidly decaying calcium oscillations
      continued through at least the first five cleavages in specimens that developed
      into normal blastulae, and unlike fertilization-induced calcium waves, such
      spikes tended to be more pronounced in the cortical cytoplasm during early
      cleavages. Thus, three different types of calcium dynamics--no marked transients,
      a single nonoscillating wave, and repetitive oscillations--were observed as
      normally developing starfish underwent prefertilization maturation,
      fertilization, and cleavage, respectively, suggesting that the spatiotemporal
      patterns of calcium spiking can change during starfish early development. In
      specimens microinjected with colchicine, calcium transients were also visible in
      the absence of cell divisions, indicating that calcium spiking can be uncoupled
      from cytokinesis. To assess whether calcium fluxes are required for normal
      development, oocytes were also treated with heparin to block calcium release
      mediated by inositol 1,4,5-trisphosphate (IP3). Injections of heparin, but not
      the control molecule de-N-sulfated heparin, caused abnormal fertilization-induced
      calcium dynamics in a dose-dependent fashion and typically abolished marked
      postfertilization calcium oscillations and normal cleavage. Based on correlative
      studies using caged IP3, heparin interfered with IP3-mediated calcium release,
      suggesting that such release is involved in the production of the free calcium
      elevations that occur in normally developing starfish embryos.

PMID- 7649380
TI  - Differential effect of activators of protein kinase C on cytoskeletal changes in
      mouse and hamster eggs.
AB  - Treatment of metaphase II-arrested hamster eggs with activators of protein kinase
      C has been reported to promote resumption of the cell cycle, second polar body
      emission, and pronucleus formation (G.I. Gallicano, S.M. Schwarz, R.W. McGaughey,
      and D.G. Capco, 1993, Dev. Biol. 156, 94-106). In contrast, we have not observed
      these responses in mouse eggs obtained from CF-1 mice treated with these
      activators. In this report, we evaluated if this difference was due to
      differences in the technique used for PKC stimulation in the two different
      laboratories or due to species differences. Metaphase II-arrested hamster or
      mouse eggs were treated with phorbol diesters for 5 min or with a membrane
      permeable diacylglycerol for 1 hr. Treatment of hamster eggs resulted in (1) the
      formation of "second polar body-like structures" commencing 5 min after treatment
      and reaching a maximum by 20-40 min; (2) a remarkable increase in the staining of
      filamentous actin in the region of these polar body-like structures; and (3) the
      disassembly of spindle microtubules. A reduction in cdc2/cyclin B1 kinase
      activity, as assessed by a decrease in H1 kinase activity, as well as progression
      from metaphase to anaphase were not observed. Treatment of mouse eggs from either
      CF-1 or CD-1 mice with these activators of PKC did not result in the formation of
      these polar body-like structures, did not cause an increase in filamentous actin,
      and did not result in a reduction in histone H1 kinase activity. This treatment,
      however, did induce disassembly of the spindle microtubules and the formation of
      multiple "pronucleus-like structures" that were more discernible in eggs from CD
      1 mice. We conclude that the "apparent" activation of hamster eggs by activators
      of PKC is due to the effect of these agents on the cytoskeleton, which gives rise
      to structures that appear similar to polar bodies, but without any evidence of
      cell cycle resumption. The different responses seen in mouse and hamster eggs are
      mainly due to differences in the sensitivity of the cytoskeleton to
      rearrangements induced by these agents.

PMID- 7649381
TI  - Diversification of cardiomyogenic cell lineages in vitro.
AB  - The ability of undifferentiated cardiogenic mesoderm to generate diversified
      myogenic phenotypes was assayed in a minimal culture system. During cardiogenesis
      in vivo, the anterior and posterior segments of the avian heart have distinct
      patterns of contractile protein gene expression when they first differentiate. To
      assess the potential of undifferentiated cardiogenic tissue to diversify into
      distinct anterior and posterior lineages prior to heart formation, cardiogenic
      mesoderm and endoderm were removed together from the embryo at Hamburger and
      Hamilton stages 4-8. Explants from each of these stages differentiated in defined
      medium as indicated by the expression of muscle-specific genes. However, the
      ability to express the atrial-specific myosin heavy chain (AMHC) mRNA was
      confined to posterior cardiac progenitors. Diversification was not dependent on
      anterior endoderm, suggesting that inductive interactions between the mesoderm
      and endoderm are not necessary to maintain diversified cardiac lineages after
      stage 4. The diversified potential of explanted cardiogenic tissue was altered
      with retinoic acid treatment, resulting in the activation of AMHC1 gene
      expression in the anterior progenitors. Anterior cardiogenic cells removed from
      the embryo at stage 8, when the heart begins to differentiate in vivo, are not
      susceptible to the alteration of diversified phenotype by retinoic acid
      treatment. Therefore, the potential to form distinct cardiomyogenic cell lineages
      is present in the anterior lateral plate mesoderm soon after gastrulation and the
      maturation of these lineages in a positionally dependent manner is maintained in
      a simple defined culture system in vitro.

PMID- 7649382
TI  - MRC-5 cells induce the AER prior to the duplicated pattern formation in chick
      limb bud.
AB  - We have previously shown that MRC-5 cells induce the duplication of the chick
      limb bud following the implantation into the anterior limb bud only during pre
      limb-bud stages. We now report the process of duplicated pattern formation caused
      by MRC-5 cells. The duplicated patterns are also formed following the
      implantation into the center of the limb bud and an excess apical ectodermal
      ridge (AER) with Msx2 expression is induced prior to these duplicated pattern
      formulations. Only after the implantation into the anterior leg bud, the shh gene
      is expressed additionally in the anterior leg bud and the mirror-symmetric
      duplication along the anteroposterior (A-P) axis is formed. The map of the
      polarizing activity in stage 21 embryo suggests that the high polarizing activity
      of the normal flank region is responsible for the changes in the A-P polarity
      when MRC-5 cells are grafted into the anterior leg bud. These results indicate
      that MRC-5 cells induce the AER and that the excess AER produces the duplicated
      cartilage pattern of the limb bud.

PMID- 7649383
TI  - Wnt-4 expression induces a pregnancy-like growth pattern in reconstituted mammary
      glands in virgin mice.
AB  - Expression of Wnt-4, a member of the Wnt gene family, is induced during early
      pregnancy in the mouse mammary gland. To investigate the function of Wnt-4, we
      used a recombinant retrovirus to constitutively express the gene in transplanted
      mammary epithelium grown in virgin animals. In fully grown glands, Wnt-4
      expression resulted in ducts that were more highly branched than normal and
      caused some premature alveolar development. These changes resembled those seen
      during pregnancy, suggesting that endogenous Wnt-4 expression may regulate
      epithelial branching in early pregnancy. The modified growth pattern induced by
      Wnt-4 expression was similar to that induced by Wnt-1, one of the members of the
      Wnt gene family activated by mouse mammary tumour virus. As Wnt-1 is not normally
      expressed in the mammary gland, it may exert its effect on the mammary gland by
      activating a developmental pathway normally regulated by Wnt-4.

PMID- 7649384
TI  - Variable cell positions and cell contacts underlie morphological evolution of the
      rays in the male tails of nematodes related to Caenorhabditis elegans.
AB  - As a first step toward understanding their mechanism of morphological evolution,
      we compare the morphology and development of the male genitalia in 10 species of
      Rhabditidae, the family of nematodes that includes Caenorhabditis elegans. We
      describe a number of variable morphological characteristics and focus in
      particular on the differing arrangements of the caudal papillae or rays within
      the acellular fan. We analyze the development of the ray cells within the
      epidermis of the last larval stage and identify changes in cell positions and
      cell contacts that underlie evolutionary changes in the arrangement of the rays.
      Epidermal cell positions were determined by means of indirect immunofluorescence
      staining with a monoclonal antibody directed towards adherens junctions.
      Similarities between the species in the cellular arrangements during the earliest
      developmental stages allow us to propose homologies between the rays in different
      species. Evolutionary changes in the positions and order of homologous rays are
      correlated with shifts in cell positions during development. The results suggest
      that genes for cell recognition or adhesion proteins, or pattern formation genes
      that regulate cell recognition or adhesion proteins, may be important foci of
      evolutionary change affecting morphology.

PMID- 7649385
TI  - The LIM class homeobox gene lim5: implied role in CNS patterning in Xenopus and
      zebrafish.
AB  - LIM homeobox genes are characterized by encoding proteins in which two cysteine
      rich LIM domains are associated with a homeodomain. We report the isolation of a
      gene, named Xlim-5 in Xenopus and lim5 in the zebrafish, that is highly similar
      in sequence but quite distinct in expression pattern from the previously
      described Xlim-1/lim1 gene. In both species studied the lim5 gene is expressed in
      the entire ectoderm in the early gastrula embryo. The Xlim-5 gene is activated in
      a cell autonomous manner in ectodermal cells, and this activation is suppressed
      by the mesoderm inducer activin. During neurulation, expression of the lim5 gene
      in both the frog and fish embryo is rapidly restricted to an anterior region in
      the developing neural plate/keel. In the 2-day Xenopus and 24-hr zebrafish
      embryo, this region becomes more sharply defined, forming a strongly lim5
      expressing domain in the diencephalon anterior to the midbrain-forebrain
      boundary. In addition, regions of less intense lim5 expression are seen in the
      zebrafish embryo in parts of the telencephalon, in the anterior diencephalon
      coincident with the postoptic commissure, and in restricted regions of the
      midbrain, hindbrain, and spinal cord. Expression in ventral forebrain is
      abolished from the 5-somite stage onward in cyclops mutant fish. These results
      imply a role for lim5 in the patterning of the nervous system, in particular in
      the early specification of the diencephalon.

PMID- 7649386
TI  - Developmental changes in the distribution of the endoplasmic reticulum and
      inositol 1,4,5-trisphosphate receptors and the spatial pattern of Ca2+ release
      during maturation of hamster oocytes.
AB  - During maturation of hamster oocytes, the distribution of the endoplasmic
      reticulum (ER) and inositol 1,4,5-trisphosphate receptors (InsP3Rs) was found to
      change dramatically, as observed using confocal microscopy with DiI and electron
      microscopy for the ER and immunohistochemistry for InsP3Rs. In immature oocytes
      at the germinal vesicle (GV) stage, ER and InsP3Rs were located predominantly in
      several large masses near the surface and also in the perinuclear region near the
      surface. In contrast, fine ER networks and low-density InsP3Rs were present in
      the inner cytoplasm. The ER appeared to be formed as vesicles from annulate
      lamellae (AL) in the subcortical area. Rises in Ca2+ concentration occurred in
      the cytoplasm and the GV when immature oocytes were inseminated, but clear Ca2+
      waves did not occur. Ca2+ rises began preferentially from the perinuclear region
      in response to low doses of serotonin or to uniform stimulation of InsP3Rs with
      photocleavage of caged InsP3. Serum also induced inhomogeneous Ca2+ release,
      shown by nonpropagating Ca2+ rises at multiple surface sites. Between the GV
      stage and prometaphase I the number and size of the surface ER masses increased,
      and the AL disappeared. This quantitative ER maturation was followed by a second
      step, spatial maturation. After prometaphase I, surface ER masses gradually
      dispersed to a number of much smaller ER clusters near the surface and, together
      with the perinuclear mass, were incorporated into thicker ER networks, resulting
      in a reticular pattern of the ER with small patches of InsP3Rs throughout the
      mature egg. The ER shifted to the peripheral surface with apposition to cortical
      granules. These developmental changes in ER Ca2+ stores may account, at least
      partly, for the acquisition of the ability of an egg to undergo normal
      fertilization.

PMID- 7649387
TI  - Reorganization of the endoplasmic reticulum during meiotic maturation of the
      mouse oocyte.
AB  - The endoplasmic reticulum (ER) of live metaphase II mouse eggs and prophase I
      arrested oocytes was compared using the fluorescent, lipophilic dicarbocyanine
      dye, DiI. DiL, dissolved in soybean oil, was microinjected into oocytes and eggs;
      the dye diffused throughout the cytoplasm to label the ER, which was imaged by
      confocal microscopy. The mature egg had a fine reticular network of ER throughout
      the cell and numerous dense accumulations of membrane in the cortex. These ER
      accumulations, 1-2 microns in diameter, were generally absent deeper in the
      cytoplasm. A similar staining pattern was observed when the eggs were fixed
      within 1 min of injection, providing evidence that the cortical accumulations of
      membrane are part of a continuous ER membrane system, since membrane trafficking
      could not occur in a fixed egg. Cortical ER accumulations were localized to the
      same region of the egg as the cortical granules and were not observed in the
      cortical granule-free region adjacent to the meiotic spindle. In contrast, ER
      accumulations were rarely found in the cortex of the immature, prophase I
      arrested oocyte, but larger and less well-defined membrane clusters were found
      throughout the deeper cytoplasm of the oocyte. The appearance of ER clusters in
      the egg cortex following oocyte maturation correlates with an increased ability
      of the mature egg to release calcium at fertilization. Since the ER is a calcium
      store, structural reorganization of the ER may be necessary to permit the large
      release of calcium and resulting cortical granule exocytosis at fertilization.

PMID- 7649388
TI  - Molecular cloning and immunological analysis of goldfish cyclin A during oocyte
      maturation.
AB  - Cyclin A belongs to a family of proteins involved in the regulation of the
      eukaryotic cell cycle. Although cyclin A is thought to be involved in the
      regulation of both S and M phase, its exact role in the cell cycle, especially in
      the meiotic cycle (oocyte maturation), is uncertain. We isolated cyclin A cDNA
      clones from a goldfish oocyte cDNA library. Monoclonal antibody raised against
      bacterially produced goldfish cyclin A recognized a 47-kDa protein that
      disappeared after egg activation. Unlike goldfish cyclin B, which is absent in
      immature oocytes, cyclin A was already present in immature oocytes and its
      protein level did not change remarkably during oocyte maturation. These results
      differ from the finding in Xenopus, in which cyclin A is absent, but cyclin B is
      present, in immature oocytes. Goldfish cyclin A was associated with cdc2 kinase
      in mature oocytes, but not with cdk2. Recombinant cyclin A bound to and activated
      cdc2 in a cell-free system, but cyclin A and cdk2 binding was not observed. The
      kinase activity of cyclin A-cdc2 was undetectable in immature oocytes and first
      appeared at about the time of germinal vesicle breakdown (GVBD). In contrast to
      the cyclin B-cdc2 activity that corresponded to the occurrence of GVBD, cyclin A
      cdc2 activity increased only slightly until GVBD was completed and increased
      drastically after the completion of the first meiotic division. Furthermore,
      microinjection of cyclin A mRNA into immature oocytes did not cause GVBD;
      however, microinjection of cyclin B mRNA did. These results suggest that cyclin A
      cdc2 kinase and cyclin B-cdc2 kinase play different roles in controlling oocyte
      maturation. The roles of cyclin A in the rapid activation of cyclin B-cdc2 kinase
      at meiosis I and II transition and in the maintenance of high maturation
      promoting factor activity in mature unfertilized eggs are discussed.

PMID- 7649389
TI  - Light and development regulate the expression of the albino-3 gene in Neurospora
      crassa.
AB  - The albino-3 gene of Neurospora crassa codes for geranylgeranyl pyrophosphate
      synthase, an enzyme involved in the biosynthesis of carotenoids. The albino-3
      locus encodes two overlapping transcription units that give rise to two mRNAs of
      2.2 kb (al-3(c)) and 1>6 kb (al-3(m)), with the promoter of the latter residing
      in the transcribed region of the former. The 1.6-kb transcript was transiently
      expressed in the mycelium after light induction, while the 2.2-kb mRNA appeared
      in conidiating cultures only, independently of light. Al-3(c) mRNA was enhanced
      in the conidiophores and was impaired in mutants blocked at the early stages of
      conidiation; al-3(c) therefore represents a conidiation-specific transcript. The
      al-3(c) mRNA level increased upon illumination with blue light and fluctuated
      according to the circadian cycle.

PMID- 7649390
TI  - Evidence for engrailed-independent wingless autoregulation in Drosophila.
AB  - Proper spatial expression of the wingless (wg) gene in the Drosophila embryonic
      epidermis is crucial to intrasegmental patterning. Single cell wide wg expression
      is initiated at the blastoderm stage in response to combinatorial regulation by
      the pair rule genes. Later, during gastrulation, when the epidermal expression of
      the pair rule genes has disappeared, wg becomes regulated by the activity of the
      segment polarity genes. The segment polarity gene engrailed (en) is expressed in
      cells adjacent to the wg-expressing cells and is required to maintain wg
      transcription. Since wg is in turn required to maintain en expression, wg appears
      to autoregulate its own expression through an endependent paracrine feedback
      loop. In this paper, we demonstrate that wild-type wg expression requires wg
      activity during stage 9, prior to its requirement for en maintenance, indicating
      that wg has an autoregulatory role that is distinct from its paracrine feedback
      loop through en. In addition, by misexpressing Wg and En in distinct spatial
      patterns in the epidermis, we find that En is capable of inducing expression from
      the endogenous wg gene only in immediate adjacent cells which have been exposed
      to Wg. Furthermore, exogenous Wg expression enables maintenance of endogenous wg
      transcription in both wg and en mutant embryos. Our results support the model
      that in the wild-type embryo, wg has an autoregulatory function which is distinct
      and separable from paracrine regulation via en. We also provide evidence that
      late, localized Wg expression is crucial for the asymmetric patterning of
      epidermal cell types as reflected in the larval cuticle.

PMID- 7649391
TI  - The development of haematopoietic cells is biased in embryonic stem cell
      chimaeras.
AB  - The haematopoietic development of embryonic stem (ES) cell injection chimaeras
      was analysed using beta-galactosidase expression from an X-linked transgene as a
      marker to distinguish the ES-derived cell population from the host cells. The
      number of cells in the different haematopoietic cell subpopulations was
      determined by flow cytometry. When the proportions of ES-derived cells in the
      antigen-positive lineages were compared to the ES cell contribution to all cells
      in teh organs, we found an unexpected bias in the haematopoietic differentiation
      of ES-derived cells. ES descendants were overrepresented in the bone marrow B
      lymphoid cell population and the splenic myeloid cells but were underrepresented
      in the CD4-positive T lymphoid cells in the spleen. These results were obtained
      by comparison with control female animals that were X chromosome mosaic for beta
      galactosidase expression. These findings of uneven contribution to haematopoietic
      development by ES cells indicate that the commitment of ES cell descendants may
      be different from that of the host cells.

PMID- 7649392
TI  - Expression of the novel basic helix-loop-helix gene eHAND in neural crest
      derivatives and extraembryonic membranes during mouse development.
AB  - We employed the yeast two-hybrid technique to screen a mouse embryo cDNA library
      for novel tissue-specific Class B basic helix-loop-helix (bHLH) transcription
      factors, which heterodimerize with the ubiquitously expressed Class A bHLH
      protein E12. From this screen, we cloned a novel bHLH protein, which we named
      eHAND. Its low sequence identity with other bHLH family members and unique
      expression pattern during development suggest that eHAND defines a new subclass
      of Class B bHLH proteins. eHAND was expressed at high levels in trophoblast cells
      and extraembryonic membranes throughout development. The first site of eHAND
      expression in embryos was the heart, where it was expressed at high levels
      between 8.5 and 10.5 days post coitum (d.p.c.), after which transcript levels
      declined abruptly. By 13.5 d.p.c., eHAND expression in the heart was localized to
      regions of valve formation. Expression in other regions of the embryo was
      confined to tissues with a substantial neural crest component. eHAND was
      expressed in the first branchial arch and its derivatives, in the sympathoadrenal
      lineage, and in the enteric systems. The expression pattern of eHAND during
      development is distinct from that of other bHLH genes and suggests that it has a
      role in formation of extraembryonic tissues, heart, and neural crest derivatives.

PMID- 7649393
TI  - Mutations in the Caenorhabditis elegans gene vab-3 reveal distinct roles in fate
      specification and unequal cytokinesis in an asymmetric cell division.
AB  - Asymmetric cell divisions in which a precursor cell distributes fate potential
      unequally between the two daughter cells represent one of the major mechanisms
      for fate specification during development. Such mechanisms suggest at least two
      distinct cellular activities: factors that act to establish asymmetry in the
      precursor cell and factors that are distributed or activated unequally and
      function to make the daughter cells different from each other. In Caenorhabditis
      elegans, cytokinesis of the first division of the male-specific postembryonic
      blast cell B is unequal, and the two daughters adopt different fates. Others have
      observed that the genes lin-17 and lin-44 are required, respectively, to
      establish and to orient this asymmetric division. Mutations in lin-17 and lin-44
      coordinately disrupt cytokinesis and fate specification. We describe the function
      of the gene vab-3 in the B cell lineage. Mutations in vab-3 disrupt the fate of
      the anterior daughter of B, B.a. However, unlike lin-17 and lin-44, mutations in
      vab-3 can disrupt fate without the corresponding disruption of unequal
      cytokinesis. Analysis of lin-17;vab-3 double mutants suggests that vab-3 acts
      after lin-17 for B.a. fate specification. Double mutant analysis has also
      identified additional functions of lin-17 in the B lineage subsequent to this
      first division.

PMID- 7649394
TI  - Proteases stimulate fertilization-like responses in starfish eggs.
AB  - Application of proteases to eggs of the starfish, Asterina miniata, caused
      several responses like those seen at fertilization. Cortical granule exocytosis
      and fertilization envelope elevation occurred within about 1 min after exposure
      to trypsin, chymotrypsin, or pronase; protease inhibitors prevented these
      responses. Kallikrein caused cortical granule exocytosis and fertilization
      envelope elevation, but this response required more time (congruent to 30 min).
      Exocytosis was also seen in response to a recombinant trypsin, but not to a point
      mutated trypsin without proteolytic activity. The extent of exocytosis was
      similar to that seen at fertilization, as measured by the fluorescent dye FM 1
      43. In addition to causing exocytosis, application of trypsin, chymotrypsin, or
      pronase caused an increase in intracellular free calcium, detected by calcium
      green dextran, and stimulation of DNA synthesis, detected by incorporation of
      bromodeoxyuridine. Exocytosis also occurred when trypsin or chymotrypsin was
      applied in artificial sea water in which the free calcium was reduced to a low
      level (40-70 nM) such that Ca influx would be reduce by > 10,000-fold; this
      indicated that the proteases did not act by damaging the eggs and causing
      external calcium to leak into the cytoplasm. These findings show that there is an
      extracellularly exposed protein that when proteolyzed can induce fertilization
      like responses; this protein may be a receptor that transduces a signal from the
      sperm to initiate egg activation at fertilization.

PMID- 7649395
TI  - Characterization and developmental expression of Pax9, a paired-box-containing
      gene related to Pax1.
AB  - Pax9, a recently identified mouse paired-box-containing gene, is highly
      homologous to Pax1 and belongs to the same subfamily as Pax1, Hup48, PAX9, and
      pox meso. Two overlapping cDNA clones spanning the entire coding region of Pax9
      were isolated and sequenced. A comparison of the Pax1 and -9 protein sequences
      reveals a high degree of similarity even outside the paired box, while the
      carboxy-terminus of the two proteins diverges completely. We demonstrate that
      Pax9 can bind to the e5 sequence from the Drosophila even skipped promoter, which
      is also recognized by Pax1. We analyzed the expression of Pax9 during
      embryogenesis of wildtype, Undulated short-tail (Uns), and Danforth's short tail
      (Sd) mice. In wildtype embryos Pax9 is expressed in the pharyngeal pouches and
      their derivatives, the developing vertebral column, the tail, the head, and the
      limbs. Expression of Pax9 is unaffected in Uns embryos, in which the Pax1 gene is
      deleted, arguing that expression of Pax9 is not dependent on Pax1. The expression
      of Pax9 is lost in the caudal part of Sd homozygous embryos, suggesting that
      expression of Pax9 in the vertebral column is dependent on the notochord. These
      results indicate that both Pax9 and -1 may act in parallel during morphogenesis
      of the vertebral column.

PMID- 7649396
TI  - Functional conservation of the Wnt signaling pathway revealed by ectopic
      expression of Drosophila dishevelled in Xenopus.
AB  - Wnt genes encode secreted growth factors that exhibit potent effects on both
      embryonic and postembryonic development in vertebrates and invertebrates.
      Recently, the dishevelled (dsh), shaggy/zeste-white 3, and armadillo genes have
      been shown to participate in Wnt (wingless; wg) signaling in Drosophila.
      Vertebrate genes that have sequence similarities to all of these Drosophila genes
      have been identified. To determine whether these structurally conserved
      components of insect wg signaling represent a functionally conserved Wnt
      signaling pathway in vertebrates, we investigated the role of Drosophila dsh in
      Xenopus Wnt signaling. Xenopus embryos ectopically injected with Drosophila dsh
      mRNA developed duplicated axes similar to those seen in embryos injected with Wnt
      mRNAs. The involvement of dsh function in the Wnt signaling pathway in Xenopus
      was demonstrated using two assays which are specifically sensitive to Wnt
      signaling: synergistic induction of dorsal mesoderm with bFGF and the specific
      induction of a Wnt-responsive reporter gene. These findings support the notion
      that the intracellular response to the Wnt signal has been conserved during
      evolution to such an extent that its components may be interchanged between
      distantly related species.

PMID- 7649397
TI  - Purification of mouse primordial germ cells by MiniMACS magnetic separation
      system.
AB  - During migration toward gonadal ridges, primordial germ cells (PGCs; the earliest
      identifiable germ cells in the embryo) are very few in number, move along
      different tissues, and are not identifiable by morphological criteria alone. Here
      we report the use of the magnetic cell sorter MiniMACS as a tool for the
      isolation of such rare cells from 10.5- to 13.5-days post coitum mouse embryos.
      Cells stained sequentially by TG-1 (a monoclonal IgM antibody known to bind to
      the surface of PGCs) and superparamagnetic microbeads coated with secondary anti
      mouse IgM antibody were separated on a magnetic column. Unlabeled cells (somatic
      cells) pass through the column, while labeled cells (germ cells) are retained.
      The retained cells can be eventually easily eluted and immediately used for
      biochemical studies or grown in suitable in vitro culture systems.

PMID- 7649398
TI  - A nuclear GFP that marks nuclei in living Drosophila embryos; maternal supply
      overcomes a delay in the appearance of zygotic fluorescence.
AB  - The central role of gene expression in regulating development has largely been
      studied by in situ hybridization and antibody staining techniques in fixed
      material. However, rapid temporal and spatial changes in gene expression are
      often difficult to correlate with complex morphogenetic movements. A green
      fluorescent protein (GFP) from the jellyfish, Aequorea victoria, can be used as a
      real-time reporter for gene expression and could aid analysis of dynamic events
      during embryogenesis. Here, we describe a transgenic Drosophila line ubiquitously
      expressing a nuclear GFP fusion protein that highlights morphogenesis, cell
      movement, and mitosis in living embryos. The fusion protein is highly fluorescent
      when maternally supplied, but there is a long delay between its zygotic
      expression and the appearance of fluorescence. GFP is thus an excellent marker
      for the expression of stable gene products, but a poor reporter for dynamic
      zygotic gene expression in early Drosophila embryos.

PMID- 7649399
TI  - Postmeiotic transcription of X and Y chromosomal genes during spermatogenesis in
      the mouse.
AB  - During the meiotic prophase of spermatogenesis, the X and Y chromosomes form the
      heterochromatic sex body, showing little transcriptional activity. It has been
      suggested that transcription of the Xist gene is involved in this inactivation.
      After completion of the meiotic divisions, at least two Y chromosomal genes, Zfy
      and Sry, are transcribed in haploid spermatids. In contrast, postmeiotic
      transcription of X chromosomal genes has not been demonstrated. Using highly
      purified preparations of mouse pachytene spermatocytes, round spermatids, and
      cytoplasmic fragments from elongated spermatids, the present experiments show
      differential postmeiotic expression of the Y chromosomal genes Ubely and Sry,
      with highest mRNA levels in round spermatids and cytoplasmic fragments,
      respectively. Postmeiotic transcription of the X chromosomal gene Ube1x is
      indicated by an increased level of Ube1x mRNA in round spermatids and cytoplasmic
      fragments. The X chromosomal gene MHR6A shows a marked temporary postmeiotic
      expression in round spermatids. This postmeiotic activity of the X chromosome is
      a novel finding, which may have implications for our understanding of X
      chromosome inactivation during spermatogenesis and paternal genome imprinting.

PMID- 7649400
TI  - European Pancreatic Club (EPC) XXVIIth meeting. Barcelona, Spain, June 28-July 1,
      1995. Abstracts.

PMID- 7649401
TI  - Protein Motifs. 7. The four-helix bundle: what determines a fold?
AB  - The four-helix bundle motif occurs in many structural contexts and in proteins
      that are functionally diverse. The motif can be classified into individual folds
      on the basis of topological and geometric properties. It has been thoroughly
      investigated structurally by both nuclear magnetic resonance and x-ray
      crystallography. Many mutants of four-helix bundles have been generated, and the
      motif has also been the target of de novo design studies. Taken together, these
      studies provide an opportunity to examine many of the forces governing protein
      folding. In this article we consider the relative importance of the burial of
      hydrophobic residues, loss of conformational entropy, packing interactions,
      interhelical turn composition, and helical dipole interactions all within the
      context of a single folding motif. We conclude by examining why de novo designed
      four-helix bundle proteins possess flexible interiors, and possible mechanisms by
      which natural proteins may lock their cores into rigid structures.

PMID- 7649402
TI  - Hypermodified bases in DNA.
AB  - Modified DNA bases are widespread in nature. They can be found in eukaryotes,
      prokaryotes, and bacteriophages. They may completely replace the standard base or
      replace only a small fraction. Their substituents vary from simple methyl or
      hydroxy groups to large moieties like amino acids and multiply hexosylated side
      chains. This review gives an overview of the modified DNA bases identified thus
      far, with emphasis on the "very unusual" or hypermodified DNA bases. Although
      these have been detected mainly in bacteriophages, recent work has shown the
      presence of a novel hypermodified DNA base in the eukaryote Trypanosoma brucei.
      We speculate on the biosynthesis and function of this novel base beta-D-glucosyl
      hydroxymethyluracil.

PMID- 7649403
TI  - Mechanisms of DNA damage recognition in mammalian nucleotide excision repair.
AB  - The ability of nucleotide excision repair (NER) to process multiple forms of DNA
      damage is highly dependent on the precision by which DNA modifications are
      located in the genome. Studies of mammalian NER have shown that this system
      eliminates a wide range of chemically and structurally distinct DNA lesions
      whereby some types of damage are repaired at higher rates than others. Although
      the biochemical basis for this broad but heterogeneous response to DNA damage is
      poorly understood, recent discoveries in closely related areas of DNA metabolism
      indicate that selectivity for specific sites is achieved through the assembly of
      nucleoprotein complexes, in which DNA is frequently bent and unwound. In many
      cases, selectivity may be further enhanced by the action of specialized DNA
      helicases. These principles in protein-DNA recognition suggest a hypothetical
      mechanism of damage recognition that accounts for the wide substrate range of
      mammalian NER and also accommodates its preference for specific DNA lesions.

PMID- 7649404
TI  - Specificity of expression and effects of eicosanoid mediators in normal
      physiology and human diseases.
AB  - The eicosanoids are a family of oxygenated arachidonic acid derivatives that
      potently mediate diverse physiological and pathophysiological processes. Recent
      research on eicosanoids has revealed novel pathways of synthesis, a family of
      related cell membrane receptors, and distinctive roles in cellular functions.
      There are two cyclooxygenases that convert arachidonic acid to thromboxane and
      prostaglandins, one of which is localized in the endoplasmic reticulum and the
      other in the nuclear envelope. The cyclooxygenases differ in their susceptibility
      to inhibition by nonsteroidal antiinflammatory drugs. The leukotriene-generating
      pathway consists of a cytosolic perinuclear 5-lipoxygenase, two integral nuclear
      envelope proteins, termed 5-lipoxygenase-activating protein and LTC4 synthase,
      and a cytosolic LTA4 hydrolase. Each protein of the leukotriene synthetic pathway
      is a target for specific pharmacological intervention. Cellular recognition and
      effects of eicosanoids are mediated by at least 12 different G protein-associated
      primary receptors, which differ in tissue distribution, signaling mechanisms, and
      cellular behavior, as well as binding specificity. Transient localized increases
      in tissue concentrations of eicosanoids and the concurrent upregulation of
      complementary receptors influence differentiation, migration, and specific
      activities of cells in immunity and other integrated physiological responses.

PMID- 7649405
TI  - Structural and functional relationships of heterotrimeric G-proteins.
AB  - Heterotrimeric GTP-binding proteins (G-proteins) are a critical component of
      signal transduction pathways that carry information received at the cell surface
      to the appropriate cellular effector system, ultimately achieving a specific
      cellular response. Heterotrimeric G-proteins consist of an alpha-subunit, which
      contains the guanine nucleotide binding site and intrinsic GTPase activity, and
      an inseparable beta gamma-subunit complex. G-proteins act to define the
      specificity by which a receptor regulates a particular intracellular signaling
      system, as well as to regulate the duration of the signal. A great deal of
      structural and functional insight into how G-protein-mediated signal transduction
      occurs has recently been achieved. This review will discuss the structural
      features of G-proteins, as well as detail the mechanism by which G-proteins
      interact with receptors and effectors.

PMID- 7649406
TI  - Evidence from transgenic mice that myc regulates hepatic glycolysis.
AB  - The product of the c-myc proto-oncogene (c-Myc) is involved in the control of
      cell proliferation, differentiation, and apoptosis. It acts as a transcription
      factor that recognizes the CACGTG motif. This sequence has also been found in the
      glucose-responsive elements of genes involved in the control of liver glycolysis
      and lipogenesis. To determine whether c-Myc can regulate hepatic carbohydrate
      metabolism in vivo, transgenic mice that overexpress c-myc under control of the P
      enolpyruvate carboxykinase (PEPCK) gene promoter have been generated. These mice
      showed a threefold increase in c-Myc protein in liver nuclei. Hepatocytes from
      transgenic mice were normal and did not acquire the fetal phenotype. However,
      transgenic mice showed higher levels (threefold) of L-type pyruvate kinase mRNA
      and enzyme activity than control mice. The increase in pyruvate kinase activity
      led to a three- to fivefold increase in liver lactate content and a fivefold
      induction of lactate production by hepatocytes in primary culture. The expression
      of the 6-phosphofructo-2-kinase gene was also increased in the liver of these
      transgenic mice. The induction of hepatic glycolysis was related with an increase
      in the expression (about fourfold) and activity (about threefold) of liver
      glucokinase, whereas no change was noted in hexokinase-I. This change in
      glucokinase activity led to an increase in both glucose 6-phosphate and glycogen
      contents in the liver of transgenic mice. The expression of the liver-specific
      glucose transporter GLUT2 was also increased in transgenic mice, whereas no
      change was noted in the mRNA concentration of GLUT1. Furthermore, the changes of
      liver glucose metabolism led to a marked reduction of blood glucose (25%) and
      insulin (40%) concentrations in starvation, whereas the fall in both was only 10%
      in fed mice. Thus, liver glucose metabolism could determine the blood glucose and
      insulin set points in the transgenic mice. All these results indicated that the
      increase in c-Myc protein was able to induce liver glucose utilization and
      accumulation, and suggested that c-Myc transcription factor is involved in the
      control in vivo of liver carbohydrate metabolism.

PMID- 7649407
TI  - Accelerated growth and senescence of arterial endothelial cells expressing the
      small molecular weight heat-shock protein HSP27.
AB  - Bovine arterial endothelial cells were stably transfected with the human wild
      type (wt) HSP27 or a mutant gene (mu) encoding a nonphosphorylatable form of the
      protein. At early passage both cultural and cellular morphology were similar,
      although the vacuole content in wtHSP27 was much higher than muHSP27 cells. As
      the cultures aged, wtHSP27 cells became large, polymorphic, highly vacuolated,
      and reached senescence before muHSP27 transfected cultures, which remained small
      and polygonal with few detectable vacuoles. Vector control cells showed an
      intermediate phenotype. Tritiated thymidine incorporation studies were performed
      with multiple wtHSP27 and muHSP27 clones and the results compared with 11 vector
      control clones. The results showed an average increase in growth rate for the
      wtHSP27 cells of 3.0 +/- 0.6 times. The growth rate of eight muHSP27 clones
      showed a slight decrease. Estradiol treatment of endothelial cells resulted in an
      increase in both bovine and human HSP27, with peak expression at 100 nM.
      Treatment of the vector-transfected cells with 100 nM estradiol resulted in a
      1.44 +/- 0.18 fold increase in growth rate, which was blocked by expression of
      muHSP27. These data demonstrate a role for HSP27 in controlling the growth rate
      of endothelial cells in an estrogen-responsive manner.

PMID- 7649408
TI  - The use of fluorophore-containing spin traps as potential probes to localize free
      radicals in cells with fluorescence imaging methods.
AB  - Central to the study of free radical processes is the ability to identify and
      localize their cellular site of formation. Under the best of experimental
      conditions, spin trapping/ESR spectroscopy can only characterize intracellular
      production of specific free radicals and confocal microscopy can only localize
      the site of their formation. In this article, we report on the development of a
      fluorophore-containing nitrone, alpha-[4-[5-((2-carboxy)phenyl)-5-hydroxy-4-oxo-3
      phenyl)-2-pyrrolin+ -1-yl]phenyl]-N-(tert-butyl)nitrone sodium salt (4). This
      nitrone (4) reacts with alpha-hydroxyethyl radical with a second order rate
      constant of 1.7 x 10(5) M-1 s-1 to give a characteristic ESR spectrum. However,
      we were unable to decrease the fluorescence emission, due in part to the small
      concentration of nitroxide generated from the reaction of alpha-hydroxyethyl
      radical with nitrone (4). Using the fluorophore-containing nitroxide (7) as a
      model, we found that only 12% of the nitroxide needs to be reduced to give an
      almost 400% increase in the fluorescent emission of (7). Our findings suggest new
      approaches to the development of various fluorophore-containing nitrones that can
      both characterize specific free radicals and localize their site of intracellular
      formation.

PMID- 7649409
TI  - Genetic determinism of fiber type proportion in human skeletal muscle.
AB  - Skeletal muscle fiber type distribution is quite heterogeneous, with about 25% of
      North American Caucasian men and women having either less than 35% or more than
      65% of type I fiber in their vastus lateralis muscle. To what extent human
      skeletal muscle fiber type proportion is under the control of genetic factors is
      examined in this paper. The results summarized here suggest that about 15% of the
      total variance in the proportion of type I muscle fibers in human is explained by
      the error component related to muscle sampling and technical variance, that about
      40% of the phenotype variance is influenced by environmental factors, and the
      remaining variance (about 45%) is associated with inherited factors. These
      estimates suggest that a difference of about 30% in type I fibers among
      individuals could be explained exclusively by differences in the local
      environment and level of muscular contractile activity. However, unidentified
      genetic factors would have to be invoked to account for the observation that the
      skeletal muscle of about 25% of the North American Caucasian population have
      either less than 35% or more than 65% of type I fibers.

PMID- 7649410
TI  - Self-association of interleukin 2 bound to its receptor.
AB  - Although radioiodinated interleukin 2 (IL-2) has been used to define the binding
      characteristics of the cytokine to the alpha chain of the receptor complex, we
      have found that unsubstituted IL-2 behaves differently. Whereas previous
      investigations with radioiodinated IL-2 have shown binding to the alpha chain
      with a Kd of 10 nM, we show that unsubstituted IL-2 binds to the alpha chain but
      does not reach saturation between 100 and 1000 nM. The explanation for the
      discrepancy between the analysis of radioiodinated and unsubstituted cytokine
      involves the propensity of unsubstituted IL-2 for self-association, a property
      that is abrogated by radioiodination. The functional relevance of our findings is
      indicated by the different capacities of unsubstituted and iodinated cytokine to
      induce prolonged proliferation of human T lymphocytes.

PMID- 7649411
TI  - Selective effect of zinc on uphill transport of oligopeptides into kidney brush
      border membrane vesicles.
AB  - Based on the involvement of zinc in hydrolysis of peptides, we hypothesized that
      Zn2+ may also play a role in peptide transport. To investigate this hypothesis,
      kidney brush border membrane vesicles (BBMV) were incubated for 30 min with
      different concentrations of ZnSO4 before use in uptake studies. This incubation
      increased by twofold the overshoot uptake of 3H-Gly-L-Gln, D-Leu-125I-Tyr and 3H
      cephalexin (all high-affinity substrates for the oligopeptide/H+ symporter)
      without affecting passive and/or facilitated diffusion of these substrates. Zinc
      had no effect on the uptake of either glutamine or glucose by kidney BBMV. Among
      a group of metal ions (cobalt, iron, copper, cadmium, and manganese), only
      manganese and copper substantially stimulated the activity of the oligopeptide/H+
      symporter. DTPA (a complexing agent) inhibited dipeptide uptake, which was
      reversed by the addition of zinc to the BBMV. Zinc treatment of BBMV reduced the
      EC50 value of inhibition of 3H-Gly-L-Gln uptake by unlabeled Gly-L-Gln by twofold
      (90 +/- 8 vs. 45 +/- 4 microM). Similarly, zinc treatment of BBMV reduced the
      EC50 value for inhibition of D-Leu-125I-Tyr uptake by bestatin from 80 +/- 4 to
      40 +/- 3 mM. In conclusion, the data show that zinc has a selective effect on
      transport of nutrients into kidney BBMV. It stimulates uphill transport of
      oligopeptides by a modification of their affinity for the binding site of the
      membrane transporter.

PMID- 7649412
TI  - Depolymerase amylo-chain reaction: untying the Gordian knot of raw starch
      digestion.

PMID- 7649413
TI  - How to survive the perils of eating.

PMID- 7649414
TI  - The Internet biologist.

PMID- 7649415
TI  - Flavoprotein structure and mechanism. 4. Xanthine oxidase and xanthine
      dehydrogenase.
AB  - Xanthine oxidase and xanthine dehydrogenase are enzymes involved in the
      metabolism of purines and pyrimidines in various organisms. Their relationship to
      one another has been the subject of considerable debate, primarily because of
      their proposed roles in ischemia/reperfusion damage in tissues. Differences in
      the kinetics and oxidation-reduction behavior of the two forms are accounted for
      by the presence in the dehydrogenase of a binding site for NAD+, as well as a
      substantially lower reduction potential for the flavin FADH./FADH2 couple of the
      dehydrogenase relative to the oxidase. This review presents recent advances of
      our understanding of the biochemistry and molecular biology of these systems,
      including a model for the overall morphology of xanthine oxidizing enzymes. The
      evidence that the two enzymes represent alternate forms of the same gene product,
      in some cases reversibly interconvertible between one another, is discussed.

PMID- 7649416
TI  - [The prevalence of the Wolff-Parkinson-White syndrome in a population of 116,542
      young males].
AB  - Since 1988 to 1992 we analyzed 116,452 consecutive 12-lead electrocardiograms
      belonging to the entire cohort of 18-year old young boys resident in Padova,
      Treviso, Rovigo, Venezia, Belluno area (2,834,000 inhabitants). We identified 173
      cases of overt WPW pattern (short PR interval, delta wave, anomalous
      configuration of QRS complex) with a calculated incidence of 1.48/1000. Accessory
      pathway location was: left free wall (70 patients), right free wall (39
      patients), postero-septal (37 patients), antero-septal (15 patients) and
      undetermined (12 patients). Sixty patients (34.6%) complained of different
      symptoms as palpitations, near syncope and dizziness. Fifty-three patients
      (30.6%) went in a regular sport activity. Twenty-four hour Holter monitoring (41
      patients) and exercise stress test (43 patients) did not show sustained
      tachyarrhythmias; intermittent preexcitation was recorded in 23 and 32 patients,
      respectively. Two-dimensional echocardiogram (68 out of 173) was normal in 44
      patients, while 24 showed minor cardiac abnormalities with two major disease;
      mitral valve prolapse was diagnosed in 8 patients. On the basis of
      transesophageal (24 patients) or intracardiac (5 patients) electrophysiologic
      study, 11 patients were considered at high risk for sudden death. Eight of them
      suffered from spontaneous symptoms.

PMID- 7649417
TI  - [Oral anticoagulant therapy in dilated cardiomyopathy. Warfarin treatment results
      in subgroups of patients at risk of embolic complications].
AB  - BACKGROUND: The aim of the study was to assess the role of oral anticoagulant
      therapy in patients with dilated cardiomyopathy at risk of embolic complications.
      METHODS: We studied retrospectively two hundred thirty-six patients with dilated
      cardiomyopathy; sixty-eight cases, with intracavitary thrombosis at cross
      sectional echocardiography (17 patients), embolic episodes (22), N.Y.H.A.
      functional class IV (38), chronic atrial fibrillation (23) or with a combination
      of such conditions, were treated with warfarin. The cumulative period of exposure
      to embolic events during follow-up was 814 years in the whole population in the
      absence of anticoagulant treatment and 213 years during treatment. RESULTS: The
      rate of new embolic events was 1.6 and 0 for 100 patients-years for the two
      periods respectively. The difference was not statistically significant. No
      clinically relevant haemorrhagic complication was seen during treatment.
      CONCLUSIONS: Oral anticoagulant therapy may be safely given to subgroups of
      patients with dilated cardiomyopathy at risk of embolic episodes, following
      empirical guidelines, provided a careful clinical and laboratory monitoring is
      carried on, even if no definite conclusion may be obtained about the efficacy of
      this treatment from a non-randomized study with low rates of new embolic events.

PMID- 7649418
TI  - [Idiopathic ventricular tachycardia with onset in the verapamil-sensitive left
      ventricle: the clinical characteristics and long-term follow-up of 37 patients].
AB  - BACKGROUND: Idiopathic verapamil-responsive left ventricular tachycardia (IVRLVT)
      is a rare, well known form of ventricular tachycardia. Issues concerning long
      term prognosis, drug prophylaxis and non-pharmacological therapy are rarely
      reported in the literature. We report the long-term follow-up, the efficacy of
      various drugs in the prophylaxis and the role of catheter ablation in a large
      group of patients with IVRLVT. METHODS AND RESULTS: This retrospective study
      involves 37 patients with a mean age of 28.3 +/- 14.8 years at first IVRLVT
      episode. The tachycardia morphology was typically with a right bundle-branch
      block configuration in all cases, with left axis deviation in 33 and right axis
      deviation in 5 (one patient had the 2 morphologies). Four patients had a mitral
      valve prolapse; the remaining 33 patients had neither clinical nor
      echocardiographic signs of heart disease. Only sporadic ventricular extrasystoles
      were detected at Holter monitoring in 73% of cases; 30% of patients had positive
      criteria for the presence of late potentials at signal averaged ECG. During
      electrophysiologic study, the tachycardia could be easily induced in 91% of
      patients. Mean follow-up is 7.3 +/- 4.7 years; all patients are alive at the end
      of follow-up. A mean of 2.3 +/- 1.2 drugs was prescribed in 35 patients (94.6%);
      betablockers were effective in 66% of the cases, verapamil in 20%, class I drugs
      in 22%, class III drugs in 15%. Both the 2 patients, who never received
      prophylaxis, and the 4 who stopped medication, utilize verapamil in case of
      recurrences. Eight patients were submitted to catheter ablation, with DC shock
      the first 2 patients, with RF energy from the third on; all but one (with DC
      shock) were successfully cured. CONCLUSIONS: Long-term follow-up confirmed the
      good prognosis of this form of ventricular tachycardia; a new insight that has
      been addressed about prophylaxis is the high efficacy of betablockers in
      preventing relapse and the poor efficacy of verapamil per os in chronic
      prophylaxis. Radiofrequency catheter ablation is effective and safe, using the
      earliest ventricular potential and the pace-mapping reproducing the same
      morphology of the tachycardia in all the 12 leads as a marker to identify the
      site of RF application, and may be proposed to all patients suffering from
      frequent episodes of IVRLVT.

PMID- 7649419
TI  - [Emergency angioplasty in high-risk acute infarct].
AB  - BACKGROUND: Primary coronary angioplasty in acute myocardial infarction yields
      superior results in terms of effective vessel patency, recurrent ischemia and
      acute morbidity, as compared to intravenous thrombolysis. Despite obvious
      logistic and economic limitations, this early invasive approach could be strictly
      indicated in selected groups of patients. AIM: A prospective study to test the
      immediate and short-term results of an early invasive strategy with angioplasty
      in patients with high-risk acute myocardial infarction. METHODS: Forty-one
      consecutive patients with high-risk acute myocardial infarction were submitted to
      coronary angiography and angioplasty of the involved vessel within 12 hours of
      onset of symptoms. Twenty-eight had anterior myocardial infarction and 6 were in
      cardiogenic shock. RESULTS: Primary success was achieved in 38 patients (93%): 30
      of these were discharged without complications or further revascularization
      procedures, and none has symptoms or re-infarction at one-month follow-up.
      CONCLUSIONS: Immediate invasive treatment with angioplasty in high-risk acute
      myocardial infarction seems to achieve good results, due to both effective
      infarct vessel recanalization, and early identification of candidates to urgent
      complete surgical revascularization.

PMID- 7649420
TI  - Near infrared spectroscopy and changes in skeletal muscle oxygenation during
      incremental exercise in chronic heart failure: a comparison with healthy
      subjects.
AB  - Near infrared spectroscopy (NIRS) is a noninvasive technique of monitoring tissue
      oxygen saturation by detecting changes in tissue absorbance of two wavelengths
      (850 and 760 nm) reflecting the relative oxygenation of hemoglobin and myoglobin.
      Aim of the present study was to determine whether changes in skeletal muscle
      oxygen saturation during incremental exercise detected by NIRS can reflect an
      impared oxygen delivery and an early onset of anaerobic metabolism in patients
      with chronic heart failure (CHF). We studied 19 subjects (mean age 43 +/- 16
      years). Seven patients had a history of CHF with a diagnosis of ischemic
      cardiomyopathy (Group A) and 12 were healthy sedentary (Group B). All patients
      had a history of dyspnea on exertion (NY-HA II), peripheral edema, pulmonary
      rales and cardiac gallop sounds over the last 6 months. They were in sinus rhythm
      and stable clinical condition in the last 3 months. They were well matched
      regarding age, sex and body surface area. All subjects performed an incremental
      work rate test in a ramp pattern on a upright cycle ergometer until volitional
      fatigue. Gas exchange was measured breath by breath with a metabolic chart.
      Muscle oxygenation was determined, transcutaneously, during the exercise test
      over the vastus lateralis muscle with NIRS. At peak exercise, work rate, VO2,
      anaerobic threshold (LAT), heart rate and systolic blood pressure were
      significantly lower in Group A compared to Group B (92 +/- 28 vs 232 +/- 17
      watts; 14 +/- 2 vs 21 +/- 2 ml/kg/min; 868 +/- 225 vs 1317 +/- 354 ml/min; 149 +/
      7 vs 172 +/- 18 b/min; 145 +/- 18 vs 195 +/- 21 mm Hg, respectively; p < 0.0001
      for all). In both groups, as work rate increased, tissue oxygenation initially
      either remained constant near resting levels or decreased. In both groups, muscle
      oxygenation decreased more steeply near the work rate where lactic acidosis (LAT)
      was detected. However, patients with CHF had an earlier acceleration in muscle
      deoxygenation compared to the other group, indicating a premature onset of
      anaerobic metabolism. Moreover, Group A had a flatter increase in both heart rate
      and systolic blood pressure and a steeper slope of oxygenation profile at all
      matched workloads compared to normals (Group A: -0.13 +/- 0.03 ml/min; Group B: 
      0.06 +/- 0.015 ml/min; p < 0.0001). The LAT correlated with the work rate at
      which the rate of tissue O2 desaturation accelerated (r = 0.94; p <
      0.0001).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7649421
TI  - [A transient decrease in heart rate variability in patients with sudden
      "ischemic" death during Holter monitoring].
AB  - BACKGROUND: Mechanisms precipitating sudden death are poorly known, in spite of
      the importance to detect functional factors which may contribute to such fatal
      event. Aim of the study was to investigate the relationship between "ischemic"
      sudden death (ISD: arrhythmic death preceded by acute myocardial ischemia) and
      autonomic nervous system activity. METHODS: We analysed the tapes of 6 patients
      (pts) (5 males; 67 +/- 12 yrs) suffering ISD during Holter monitoring (HM). One
      pt had recent onset angina, 2 had unstable and 3 stable angina; none was taking
      antiarrhythmic drugs. Arrhythmias, ST segment and heart rate variability (HRV)
      were analysed by a computerized interactive HM system, in order to obtain data on
      transient ischemia and sympatho-vagal balance. RESULTS: Five pts showed
      ventricular tachyarrhythmias (2 VF, 3 VT), and 1 had a bradyarrhythmia (advanced
      A-V block) as the terminal event; all pts showed ST shift (max: 0.37 +/- 0.28 mV;
      1 with ST elevation; 4 with anginal pain) 53 +/- 35 min before ISD. SD of normal
      R-R intervals (SDNN) was 112 +/- 26 msec in the 11 +/- 8 hrs of HM, whereas it
      was 97 +/- 48 msec in the initial hour and 59 +/- 21 msec in the initial 5 min
      segment. Measurements of SDNN showed a marked decrease 5 min before the onset of
      fatal ischemic ST shift: 32 +/- 14 msec (p = 0.003). Also, pNN50 (percent of
      adjacent R-R differing > 50 msec: marker of vagal activity) was significantly
      reduced before ISD, when compared to the initial 5 min segment (from 10 +/- 5 to
      7 +/- 4%; p < 0.03). Such changes were not observed before uncomplicated (that is
      not associated with malignant arrhythmias) ST shift episodes during HM.
      CONCLUSIONS: Autonomic dysfunction, as detected by a marked decrease of HRV, is
      present in the period (5 min) immediately preceding the onset of ST shift
      precipitating ISD; simultaneous measurements of vagal signals showed similar
      changes. These data suggest that sympatho-vagal unbalance may trigger fatal
      arrhythmias during acute myocardial ischemia, hence resulting in ISD.

PMID- 7649422
TI  - [Threatened paradoxical embolism: its direct visualization by two-dimensional
      echocardiography].
AB  - We describe the case of a 67-year-old patient, who had a stroke with subsequent
      right hemiparesis two years before coming under our observation. Afterwards he
      had no more pathological manifestation until he had sudden dyspnoea and marked
      cyanosis, following a prolonged immobilization due to intervention for slipped
      disc. Symptomatology regressed rapidly, and few hours later, the patient came
      under our observation in relatively fair conditions. Echocardiography evidenced
      moderate enlargement of right heart cavities; by subcostal view we visualized the
      presence of thrombotic material crossing the foramen ovale. Color Doppler showed
      moderate tricuspid regurgitation. Pulmonary artery systolic pressure was
      estimated about 55 mm Hg. The patient was immediately anticoagulated firstly by
      heparin, and secondly by warfarin, maintaining good clinical conditions. After a
      treatment of two more weeks he could be discharged with prescription of
      indefinite anticoagulation. Before discharge an echo examination showed the
      thrombus was no longer present. Pulmonary systolic pressure was estimated about
      40 mm Hg. This is one of the rare cases of direct visualization of impending
      paradoxical embolus documented in the cardiologic literature.

PMID- 7649423
TI  - [Guidelines for the indication for orthotopic heart transplantation. The
      Cardiologists and Heart Surgeons of the Heart Transplant Group of Nord Italy
      Transplant (NITp)].

PMID- 7649425
TI  - The viable myocardium. Gruppo Italiano di Cardiologia Nucleare (ANMCO-AIMN).

PMID- 7649424
TI  - Myocardial perfusion scintigraphy with pharmacological stress. Gruppo Italiano di
      Cardiologia Nucleare (ANMCO-AIMN).

PMID- 7649426
TI  - [Hemostatic factors and family history of thrombosis in patients with a
      myocardial infarct: a case-control study. The participants in GISSI-2-Efrim.
      Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico].
AB  - We studied a series of hemostasis factors in a group of patients selected from a
      cohort of 916 patients affected by MI from the GISSI-2 study population.
      Following a case-control design, 73 patients with a family history of thrombosis
      (the presence of at least two first degree relatives affected by MI and/or stroke
      before 65 years) were matched with MI patients with no family history of
      thrombosis. Blood collection could be performed 6 +/- 1 months after the acute
      phase following MI in 53 pairs of such patients. The presence of mixed
      disulphides (MDS) was significantly higher in patients with family history than
      in controls; MDS were detected in 7 cases and only in 1 control. No difference
      was found in contrast in the distribution of fibrinogen, factor VII, factor VIII,
      vWF, protein C, protein S, AT III, HC II, PAI-1, lipoprotein (a). Nevertheless,
      independently from the family history, in the whole population of MI patients
      studied, 21 cases of suspected deficiency of protein C were found. Sixteen out of
      53 patients with family history of MI and/or stroke had a family history of MI
      only. In patients with family history of MI the t-PA antigen levels were
      significantly lower than in the control group (7.5 +/- 4.4 vs 11.1 +/- 3.5 ng/ml,
      t = -2.6, p < 0.02). In the whole population of MI patients and in patients with
      a family history of thrombosis t-PA antigen was positively correlated with PAI-1
      antigen and vWF. The correlation with PAI-1 was lost in patients with family
      history of MI.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7649427
TI  - [The evolution of medical knowledge and social changes: the panorama of the
      Italian hospital in the 19th and 20th centuries].

PMID- 7649428
TI  - [Know how to read a scientific article. 1. Why read a scientific article].

PMID- 7649429
TI  - [Severe mitral insufficiency: current surgical indications and new prospects].

PMID- 7649430
TI  - [Criteria for the production of clinical guidelines (CGL). ANMCO--the Committee
      for Clinical Research. Assoziazione Nazionale Medici Cardiologi Ospedalieri].

PMID- 7649431
TI  - Plasmid rolling circle replication and its control.
AB  - This review summarises current information on rolling circle replicating plasmids
      originally isolated from Gram-positive bacteria with a low guanine and cytosine
      content in their DNA. It focuses on the peculiar biological features of these
      small, high copy number plasmids that replicate via an asymmetric RC mechanism.
      The regulation of plasmid copy number is also discussed.

PMID- 7649432
TI  - Alterations in penicillin-binding proteins in strains of Streptococcus suis
      possessing moderate and high levels of resistance to penicillin.
AB  - We examined the penicillin-binding proteins (PBPs) of certain field strains of
      Streptococcus suis, as well as those from laboratory variants having different
      degrees of resistance to penicillin. Results indicated that (i) S. suis possesses
      three distinct groups of PBPs, arbitrarily named here PBP 1, PBP 2, and PBP 3,
      with approximate molecular weights of 97, 82, and 45 kDa respectively; (ii) PBP
      profiles of field strains of S. suis having different MICs (< or = 0.03) to 16.0
      micrograms/ml) were not uniform (PBP 2 being difficult to detect in strains whose
      MICs exceeded 0.10 micrograms/ml, and PBP 3 which exhibited shifts in molecular
      weight of approximately 5 kDa); (iii) laboratory variant PBPs 1 and 2 showed
      decreased affinity for penicillin as compared to the parent strain in antibiotic
      competition experiments, even though the PBP profiles of both were similar. We
      suggest that PBP modifications (altered molecular weight and/or decreased
      affinity for penicillin) are involved in the mechanism of resistance to
      penicillin by S. suis.

PMID- 7649433
TI  - A mutation that decreases the efficiency of plasmid R1 replication leads to the
      activation of parD, a killer stability system of the plasmid.
AB  - The silent parD (kis/kid) stability operon of plasmid R1 is normally repressed by
      the co-ordinated action of the Kis and Kid proteins. In this report it is shown
      that a mutation in repA, the gene of the plasmid replication protein, that
      reduces two-fold the copy number of the plasmid, leads to the derepression of the
      parD system. This derepression can be prevented by a suppressor mutation in copB,
      a copy number control gene of plasmid R1, that increases the efficiency of
      replication of the repA mutant. Derepression of the wild-type parD system leads
      to high plasmid stability. These data show the activation of a plasmid stability
      operon by a mutation that reduces the efficiency of wild-type plasmid
      replication.

PMID- 7649434
TI  - Analysis of the sequence of a new cryptic plasmid, pRJF2, from a rumen bacterium
      of the genus Butyrivibrio: comparison with other Butyrivibrio plasmids and
      application in the development of cloning vector.
AB  - A small cryptic plasmid, pRJF2, from Butyrivibrio fibrisolvens strain OB157 was
      isolated and sequenced. The plasmid is similar in organisation to the previously
      sequenced Butyrivibrio plasmid, pRJF1, with two open reading frames, ORF1 and
      ORF2, flanking a region tentatively identified as the replication origin, and a
      region of unknown function defined by terminal 79 bp invert repeats. The
      sequences of ORF1, ORF2, and the presumptive replication origin are highly
      conserved. The sequence between the 79, bp invert repeats is not, and is
      therefore presumed to be of lesser functional significance, although the 5' and
      3' termini are still highly conserved. The functional importance for plasmid
      replication of these regions was tested by constructing potential shuttle
      vectors, each lacking one or more of the regions of interest. When the region
      between the invert repeats was deleted and replaced by the erythromycin
      resistance gene from pAM beta 1 together with pUC18, to produce the 7.9 kb
      chimaeric plasmid pYK4, the construct was successfully transformed into E. coli
      and B. fibrisolvens by electroporation, and was stably maintained in both hosts.
      Both ORF1 and ORF2 were required for successful transformation of B.
      fibrisolvens.

PMID- 7649435
TI  - A single emm gene-specific oligonucleotide probe does not recognise all members
      of the Streptococcus pyogenes M type 1.
AB  - Serological typing of the streptococcal M protein has recently been challenged by
      a number of unique molecular methodologies based on oligonucleotide recognition
      of allelic variations within the M protein (emm) gene. In these methods,
      stringent hybridization of an oligonucleotide probe to a polymerase chain
      reaction amplified emm gene is used as confirmation of specific M type identity.
      A sample of 17 isolates from 7 previously defined distinct genotypes were tested
      using a single M1 oligonucleotide probe. Isolates from only three of the
      genotypes hybridized with the probe. The results demonstrate that a single emm
      specific oligonucleotide probe can not identify all members of M type 1, as
      defined by conventional serotyping using polyclonal antisera.

PMID- 7649436
TI  - Comparison of Borrelia isolated from UK foci of Lyme disease.
AB  - Restriction endonuclease digestion of linear borrelial chromosomal DNA showed
      that three isolates of UK Lyme disease spirochaetes differed markedly from each
      other and from published data for other isolates from North America and
      continental Europe. Analysis of linear plasmid bands revealed that UK isolates
      differed from each other in the number and sizes of the plasmids in isolates from
      different foci of UK Lyme disease. Fatty acid analysis (of fatty acid methyl
      ester (FAME) profiles) showed the UK isolates clustering together with the
      relapsing fever spirochaetes, Borrelia turicatae and Borrelia parkeri. These data
      are discussed in respect of current knowledge of Lyme borreliosis in the UK.

PMID- 7649437
TI  - Evaluation of the suitability of bis-(1,3-dibutylbarbituric acid) trimethine
      oxonol, (diBA-C4(3)-), for the flow cytometric assessment of bacterial viability.
AB  - The usefulness of oxonol (bis-(1,3-dibutylbarbituric acid)trimethine oxonol) as a
      generally applicable indicator of bacterial viability was investigated using
      untreated and killed cultures of a variety of bacterial genera. Killing methods
      involved either heat or bactericidal antibiotics. For all strains tested, the
      fluorescent dye showed significantly more intense staining of killed than
      untreated cells. The sensitivity of Aeromonas salmonicida to gentamicin was
      assessed using oxonol. Although the bacterium was shown to be sensitive to the
      antibiotic, there was a delay between the time cells lost culturability, as
      judged by numbers of colony forming units, and that for which a dead cell
      population could be detected by flow cytometry.

PMID- 7649438
TI  - The mini-exon genes of three Phytomonas isolates that differ in plant tissue
      tropism.
AB  - The tandem mini-exon gene repeat is an ideal diagnostic target for
      trypanosomatids because it includes sequences that are conserved absolutely
      coupled with regions of extreme variability. We have exploited these features and
      the polymerase chain reaction to differentiate Phytomonas strains isolated from
      phloem, fruit or latex of various host plants. While the transcribed regions are
      nearly identical, the intergenic sequences are variable in size and content (130
      332 base pairs). The mini-exon genes of these phytomonads can therefore be
      distinguished from each other and from the corresponding genes in insect
      trypanosomes, with which they are oft confused.

PMID- 7649439
TI  - Cell cytotoxicity of sodium nitrite, sodium nitroprusside and Roussin's black
      salt against Trichomonas vaginalis.
AB  - We have investigated the action of sodium nitrite and other nitrosyl complexes,
      such as sodium nitroprusside and Roussin's black salt, on the growth of
      metronidazole-sensitive and resistant strains of Trichomonas vaginalis and their
      hydrogenosomal enzymes. All three chemicals inhibited the growth of T. vaginalis:
      sodium nitrite at 8 mM, sodium nitroprusside at 1.2 mM and Roussin's black salt
      at 0.2 mM. Metronidazole-sensitive (KT9) and resistant (CDC85) isolates showed
      similar cytotoxicity against these molecules. Specific activities of
      pyruvate:ferredoxin oxidoreductase and hydrogenase and oxygen uptake rates were
      decreased in the T. vaginalis isolate treated with sodium nitrite and sodium
      nitroprusside. However, Roussin's black salt increased the specific activity of
      pyruvate:ferredoxin oxidoreductase or hydrogenase in CDC85 or KT9 cells and
      increased the oxygen uptake rate in the KT9 isolate.

PMID- 7649440
TI  - Characterization of the promoter region of a cell-adhesion protein gene derived
      from the basidiomycete Lentinus edodes.
AB  - An analysis of the 2 kb nucleotide sequence including the 5'-flanking region of a
      cell-adhesion protein-encoding gene (mfbA) isolated from the basidiomycete
      Lentinus edodes revealed that the promoter region contains a TATA box, a GC box,
      a CAAT box, a CT-rich sequence element, a TATA box, two CT-rich sequences, and a
      CAAT box, in the order, from upstream to downstream. Three major and three
      alternative transcriptional initiation sites were located 127, 129 and 131
      nucleotides and 96, 193 and 197 nucleotides downstream from the downstream TATA
      box, and all the three major sites are positioned just in the most downstream CT
      rich sequence. Three 16 bp unique sequences similar to the binding sites of
      Neurospora crassa transcriptional activator protein qa-1F (Baum et al. (1987)
      Expression of qa-1F activator protein: Identification of upstream binding sites
      in the qa gene cluster and localization of the DNA-binding domain. Mol. Cell.
      Biol. 7, 1256-1266) were present between the upstream TATA box and upstream CAAT
      box.

PMID- 7649441
TI  - NAD(+)-glycohydrolase from Streptococcus pyogenes shows cyclic ADP-ribose forming
      activity.
AB  - NAD(+)-glycohydrolase from Streptococcus pyogenes was purified by successive
      chromatography on CM Sepharose CL-6B, Sephacryl S-200 HR and hydroxyapatite. The
      purified enzyme possessed synthesis and hydrolysis activities of cyclic ADP
      ribose (cADPR), a newly found second messenger for Ca2+ mobilisation, along with
      cleavage activity of the ribose-nicotinamide bond in NAD+.

PMID- 7649442
TI  - Detection by multiplex polymerase chain reaction and typing of Chlamydia
      trachomatis isolates.
AB  - The multiplex polymerase chain reaction (PCR) was applied for the detection of
      the Chlamydia trachomatis chromosome and plasmid. The multiplex PCR demonstrated
      a sensitivity of 0.8 fg of chlamydial DNA, corresponding to the detection of
      about 5 copies of the plasmid. Analysis of 195 genital specimens collected
      randomly from a female population, showed that the multiplex PCR is more
      sensitive and rapid than culturing for detecting Chlamydia trachomatis. Moreover,
      sequencing of the II variable domain of the omp1 gene, directly from DNA of the
      clinical specimens, appears to be a simple and rapid method for determining
      serovar isolates.

PMID- 7649443
TI  - Isolation and characterization of inhibitory factors of DNA polymerase III
      holoenzyme from Escherichia coli.
AB  - We isolated fractions by Mono Q chromatography that inhibited the activity of
      Escherichia coli DNA polymerase III holoenzyme using an assay system with a
      primed single-stranded DNA template coated with single-stranded DNA binding
      protein (SSB). The inhibitory activities were inactivated by heat-treatment at
      100 degrees C for 10 min, suggesting that they are proteins. The factors did not
      inhibit the activity of RNA polymerase of Escherichia coli. The inhibitory
      effects were less potent for the activities of the large (Klenow) fragment of DNA
      polymerase I and T4 DNA polymerase than for DNA polymerase III holoenzyme. No
      degradation of single- or double-stranded DNA was observed in the fractions,
      indicating that inhibition was not due to degradation of the DNA.

PMID- 7649444
TI  - The gene encoding the biotin-apoprotein ligase of Saccharomyces cerevisiae.
AB  - We report the isolation, genomic mapping, and DNA sequence of the BPL1 gene
      encoding the biotin-apoprotein ligase of Saccharomyces cerevisiae. The gene was
      isolated by complementation of an Escherichia coli birA (biotin-apoprotein
      ligase) mutant indicating that the expressed yeast protein modified the essential
      biotinated protein of the bacterial host. The BPL1 gene encodes a protein of 690
      residues (M(r) 76.4 kDa) with strong sequence similarities to the E. coli and
      human biotin-apoprotein ligases. BPL1 was mapped to chromosome IV, is allelic to
      the previously described ACC2 gene, and encodes the major (if not the only)
      biotin-apoprotein ligase activity of S. cerevisiae.

PMID- 7649445
TI  - Protective effect of Brucella outer membrane complex-bearing liposomes against
      experimental murine brucellosis.
AB  - Liposomes of stable multilamellar type, which previously demonstrated great
      efficiency in antibiotic transport, were used in this study as transport vehicles
      of antigenic extracts of Brucella melitensis (HS: complex of
      lipopolysaccharide/phospholipids/outer membrane proteins). The incorporation of
      HS into positively charged liposomes produced a protective effect against
      experimental murine brucellosis when they were administered 1 day before or 2
      days after infection, as the number of colony-forming units in the spleen was
      reduced in relation to the untreated control group (P < 0.01). On the other hand,
      the use of HS-free or bound in liposomes with negative net charge did not produce
      a significant effect. Moreover, the incorporation of HS into cationic liposomes
      eliminated the toxicity of the lipopolysaccharide.

PMID- 7649446
TI  - The role of endonucleases in the expression of ribonuclease II in Escherichia
      coli.
AB  - Ribonuclease II (RNase II), encoded by the rnb gene, is one of the two major
      Escherichia coli exonucleases involved in mRNA degradation. Some of the
      ribonucleases implicated in this process have recently been shown to be inter
      regulated. In this paper we studied the effects of the endonucleases RNase E and
      RNase III in rnb expression. We have shown that RNase E cleaves the rnb message
      internally: when this ribonuclease is inactivated rnb mRNA accumulates with a
      concomitant increase in RNase II activity. RNase III also affects RNase II
      expression but in an indirect way. We discuss these implications for the
      regulation of mRNA degradation.

PMID- 7649447
TI  - Distribution of individual cytoplasmic pH values in a population of the yeast
      Saccharomyces cerevisiae.
AB  - Fluorescence ratio imaging microscopy using pH-sensitive fluorescent dyes makes
      it possible to evaluate statistical distribution of intracellular pH in a
      population of the yeast S. cerevisiae examined in a thin layer of suspension in a
      Petri dish. The distribution appears to fit a Gaussian curve with a half-width
      around the 0.4 pH unit. The curve became slightly narrower after resuspension in
      a strong buffer; the mean values shifted with the pH of the buffer. The shape of
      the distribution curves of both resting and growing cells in various phases of
      growth does not change significantly. Likewise, addition of 1% of glucose, 50
      microM suloctidil or 100 microM diethylstilbestrol brings about no alteration.
      The only value which clearly changes is the average cytoplasmic pH.

PMID- 7649448
TI  - Amino acid consumption by the parasitic, amoeboid protists Entamoeba histolytica
      and E. invadens.
AB  - Amino acid consumption by Entamoeba histolytica and E. invadens has been measured
      in order to assess the possible roles of amino acids as energy substrates.
      Mixtures of amino acids enhanced the growth of the parasites in complex medium
      and their survival in simple medium. The consumption of several amino acids by
      the parasites suspended in simple media was greater when glucose was absent,
      suggesting that they may act as alternative energy sources. Under these
      conditions, asparagine was consumed extremely rapidly by E. histolytica in
      particular, and arginine, leucine and threonine were used greatly by both
      species. There was also a marked consumption of aspartate, but this occurred even
      when glucose was present. These five amino acids and phenylalanine were the ones
      consumed in greatest amounts during growth of E. histolytica in complex medium.
      Under the same growth conditions, E. invadens also used asparagine, arginine,
      leucine and threonine and in addition there was a large consumption of serine and
      especially glutamate. In contrast, the aspartate concentration in the complex
      medium increased and there was also a net increase in the concentration of some
      other amino acids. Alanine was produced by both species when the parasites were
      incubated in simple medium with glucose, and in greater amounts during growth in
      complex media, suggesting that it is an end product of energy metabolism. The
      findings provide support for the suggestion that energy generation through amino
      acid catabolism may be a characteristic feature of anaerobic parasitic protists.

PMID- 7649449
TI  - Involvement of prostaglandin E2 synthesis in the intestinal secretory action of
      Escherichia coli heat-stable enterotoxin II.
AB  - The prostaglandin response of mouse intestinal epithelial cells after exposure to
      Escherichia coli heat-stable enterotoxin II was examined. The quantity of
      prostaglandin E2 produced by the intestinal cells was directly related to the
      dose of heat-stable enterotoxin II. The change in the amount of prostaglandin E2
      over time correlated to that of the volume of fluid released into the intestinal
      lumen. We then demonstrated that administration of heat-stable enterotoxin II
      into the intestinal loops of mice induced elevation of arachidonic acid and
      phosphatidic acid levels in intestinal epithelial cells. These results show that
      heat-stable enterotoxin II stimulates arachidonic acid metabolism in intestinal
      epithelial cells and that the synthesized prostaglandin E2 functions as a
      mediator of fluid secretion induced by this enterotoxin.

PMID- 7649450
TI  - Expression and purification of Clostridium perfringens beta-toxin glutathione S
      transferase fusion protein.
AB  - The beta-toxin gene from Clostridium perfringens type C was cloned and expressed
      as a glutathione S-transferase fusion protein in Escherichia coli. The DNA
      sequence was determined and compared to the type B sequence. Two nucleotide
      differences were found in the protein coding sequence, resulting in one amino
      acid difference between the two proteins. The purified beta-toxin fusion protein
      is not toxic in mice, but rabbit antiserum raised against it neutralises the
      toxic effect of C. perfringens type C culture filtrate in mice.

PMID- 7649451
TI  - An antiserum to a synthetic fimbrial peptide of Actinobacillus
      actinomycetemcomitans blocked adhesion of the microorganism.
AB  - The purpose of this study is to certify the importance of the fimbriae as an
      attachment factor of Actinobacillus actinomycetemcomitans, a human
      periodontopathic bacterium, and the significance of anti-fimbrial antibody
      function as an attachment inhibitor. Fimbrial antigen was prepared from the A.
      actinomycetemcomitans 310-a strain. Oligopeptides were synthesized according to
      the amino acid sequence of the fimbrial protein. The peptide antigen was
      conjugated with branched lysine polymer resin beads. The peptide antigen was
      suspended in PBS emulsified with incomplete Freund's adjuvant and used to
      immunize rabbits. A rabbit antiserum reacted with an approximately 54 kDa protein
      of the fimbriae protein from A. actinomycetemcomitans 310-a and with those of
      other fimbriated strains. This antiserum strongly inhibited the attachment of
      fimbriated A. actinomycetemcomitans strains to saliva-coated hydroxyapatite
      beads, buccal epithelial cells, and a fibroblast cell line, Gin-1. Such a
      synthetic fimbrial peptide antigen may be effective in inducing antibodies which
      inhibit adhesion and subsequent colonization by A. actinomycetemcomitans.

PMID- 7649452
TI  - Vibrio parahaemolyticus O serotypes from O1 to O13 all produce R-type
      lipopolysaccharide: SDS-PAGE and compositional sugar analysis.
AB  - The molecular architecture of lipopolysaccharide (LPS) isolated from all O
      serotypes of Vibrio parahaemolyticus was investigated. In gel chromatography on a
      Sephadex G-50 column, the degraded polysaccharide fraction prepared from each
      serotype LPS by mild acid hydrolysis yielded only core oligosaccharide (Frc II)
      and monosaccharide (Frc III) fractions, but no fraction (Frc I) corresponding to
      O polysaccharide chain consisting of polymeric repeating oligosaccharide units.
      Compositional sugar analysis of Frc II and III suggested that the sugar chain of
      LPS of all the serotypes of V. parahaemolyticus consisted of at most ten
      monosaccharides. Sodium dodecylsulfate-polyacrylamide gel electrophoresis of the
      LPS resulted in no doublet ladder band similar to that observed for S-type
      enterobacterial LPS. These results are compatible with the interpretation that V.
      parahaemolyticus O serotypes from O1 to O13 all produce R-type LPS, despite the
      morphologically smooth appearance, demonstrated virulence and serological O
      specificity.

PMID- 7649453
TI  - Overproduced and purified receptor binding protein pb5 of bacteriophage T5 binds
      to the T5 receptor protein FhuA.
AB  - A promotor-less oad gene of bacteriophage T5, encoding the receptor binding
      protein pb5, was cloned into pT7-3 under the control of phage T7 promoter phi 10.
      Induction with IPTG resulted in enhanced production of pb5. Upon fractionation of
      the producing cells, most of the overproduced pb5 was found in the membrane
      fraction, which was most likely due to aggregation of the protein. The minor,
      soluble fraction of pb5 specifically inhibited adsorption of T5 to its FhuA
      receptor protein. Inhibition was also seen with trace amounts of pb5, and binding
      of pb5 to FhuA appeared to be almost irreversible. Purification of pb5 from the
      cytosolic fraction was performed by FPLC using a MonoQ column. pb5, which did not
      bind to the matrix of the column, was obtained in almost pure form. The purified
      protein also inhibited T5 adsorption.

PMID- 7649454
TI  - Hydrostatic pressure promotes the acidification of vacuoles in Saccharomyces
      cerevisiae.
AB  - Application of hydrostatic pressure caused a delay or cessation of cell growth in
      Saccharomyces cerevisiae. The yeast vacuole is an acidic organelle involved in
      cellular ion homeostasis and degradation of proteins. Hydrostatic pressure
      promoted the acidification of the vacuoles in the strain IFO 2347. A pressure of
      40 to 60 MPa reduced the vacuolar pH, defined using 6-carboxyfluorescein, from
      6.05 to 5.88, while a pressure of 20 MPa did not affect the pH. Similar results
      were obtained with the strain X2180. Bafilomycin A1, a specific inhibitor of
      vacuolar H(+)-ATPase (V-H(+)-ATPase), caused a significant alkalization of
      vacuoles in the strain X2180. The pHs rose to 7.34 and 6.84 at both atmospheric
      pressure and a pressure of 40 MPa, respectively. Meanwhile, vacuolar accumulation
      of the weak base quinacrine was increased by a pressure of 40 MPa, suggesting
      that uptake of the dye was induced by the increased pH gradient across the
      vacuolar membrane.

PMID- 7649455
TI  - Characterization of a major Mycoplasma penetrans lipoprotein and of its gene.
AB  - A novel mycoplasmal species designated as Mycoplasma penetrans has been isolated
      recently from patients infected with human immunodeficiency virus. p35, a major
      antigen extracted from the membrane of this mycoplasma using Triton X-114 has
      been found to be a lipoprotein. After proteolytic treatment of p35, the sequence
      of one of the resulting peptides was determined and a corresponding
      oligonucleotide was deduced. Using this oligonucleotide as a probe the p35 gene
      was cloned and sequenced. Sequence analysis revealed an amino-terminal signal
      peptide with a potential acylation site which would result in a 35.3 kDa mature
      product. In addition, the p35 gene was followed by an open reading frame with a
      corresponding polypeptide partially homologous to p35, in particular to the N
      terminus region.

PMID- 7649456
TI  - Genomic species typing of acinetobacters by polymerase chain reaction
      amplification of the recA gene.
AB  - The recA gene has been used as a target in screening for the presence of
      acinetobacters on the genospecies level and differentiation of relevant
      acinetobacter species from one another by PCR. Primers deduced from known recA
      gene sequences of Acinetobacter calcoaceticus and Neisseria gonorrhoeae allowed
      the amplification of DNAs from all Acinetobacter genospecies. The size of the
      amplified DNA fragment from all genospecies tested was approximately 435-500 bp
      relative to DNA size markers. The amplified products were examined further by
      restriction fragment length polymorphism (RFLP) analysis. Restriction analysis
      with only two enzymes, MboI and HinfI, enabled us to identify all known
      genospecies. Since this method uses conserved recA gene sequences for primers, it
      is expected to be applicable for the identification of most bacterial species.

PMID- 7649457
TI  - The computer age: beware the loss of the narrative.

PMID- 7649458
TI  - Recognition and treatment of mental illness in primary care. Towards a better
      understanding of a multifaceted problem.

PMID- 7649459
TI  - Operationalizing a bedside pen entry notebook clinical database system in
      consultation-liaison psychiatry.
AB  - No current system of computerized data entry of clinical information in
      consultation-liaison (C-L) psychiatry has been well received or has demonstrated
      that it saves the consultant's time. The inability to achieve accurate, complete,
      systematic collection of discrete variables and data entry in the harried C-L
      setting is a major impediment to the advancement of the subspecialty and health
      services research. The hand-held Notebook computer with Windows PEN ENTRY
      MICROCARES capabilities has permitted one-time direct entry of data at the time
      of collection at the patient's bedside. Variable choice and selection enhances
      the completeness and accuracy of data collection. For example, ICD-9, Axis III
      diagnoses may be selected from a "look-up" which at the same time automatically
      assigns the appropriate code and diagnostic-related groups, (DRG) number. A
      patient narrative can be typed at the nurse's station, a chart note printed for
      the medical record, and the MICRO-CARES literature database perused with the
      printing of selected citations, abstracts, and in some cases experts'
      commentaries for the consultee. The consultant's documentation time is halved
      using the NOTEBOOK WINDOWS PEN ENTRY MICRO-CARES software, with the advantage of
      more accurate and complete data description than with the traditional handwritten
      consultation records. Consultees preferred typewritten in contrast to handwritten
      notes. The cost of the hardware (about $2000) is less than that of an optical
      scanner, and it permits report generation and archival searches at the nurses'
      station without returning to the C-L office for scanning. Radio frequency or
      ethernet download from the Notebook permits direct data transfer to th C-L office
      archive computer.

PMID- 7649460
TI  - Recognition of emotional distress in physically healthy primary care patients who
      perceive poor physical health.
AB  - This study examines the recognition and treatment of emotional distress in
      physically healthy primary care patients who perceive themselves to be in fair or
      poor physical health. Patients (N = 892) from three private primary care
      practices completed a mental health screening form prior to their medical visit
      which included an overall assessment of their physical health (1 = excellent, 2 =
      good, 3 = fair, 4 = poor). Following the visit, their physicians completed a
      questionnaire that included the same physical health assessment item. The study
      group, physically healthy patients who perceive poor physical health (HPPPH),
      included those patients who rated their physical health as 2 or 3 points more
      impaired than it was rated by their physician. HPPPH (N = 39) were significantly
      more likely than other patients (N = 853) to report a prior psychiatric
      hospitalization (p < 0.05), marital difficulties (p < 0.01), recent missed work
      due to a mental health problem (p < 0.001), and a range of anxiety, depressive,
      and psychosomatic symptoms. However, HPPPH were also significantly more likely
      than other patients to receive excellent emotional health ratings (p < 0.001)
      from their physicians and were less likely to receive mental health treatment (p
      < 0.05). Detection of emotional distress may be particularly difficult in
      physically healthy patients who have low physical health perceptions.
      Identification of pessimistic physical health perceptions may serve as an
      indicator for underlying emotional distress.

PMID- 7649461
TI  - Prediction of length of stay in an inpatient dual diagnosis unit.
AB  - The institution of prospective payment systems, in which flat fees are paid per
      discharge, raised the concern that hospitals might preferentially admit patients
      expected to have a short length of stay (LOS). This concern presupposes that
      intake workers could accurately predict psychiatric hospitalization LOS, but this
      does not appear to have been empirically demonstrated. Accordingly, we examined
      the ability of two psychiatrists heading separate treatment teams on an
      inpatient, dual-diagnosis unit and a program coordinator who worked with both
      teams to predict LOS for 94 patients consecutively admitted to one or the other
      of these teams. Predictions were highly consistent across the raters and were
      significantly correlated with actual LOS (r = 0.25, 0.35, and 0.45 for the three
      raters). However, we found that the psychiatrists were accurate predictors only
      for patients for whom they were the attending psychiatrist. The program
      coordinator, who was involved in the treatment of all patients, was an accurate
      predictor for the patients of either psychiatrist. We concluded that the
      relationships found between predicted and actual LOS held true only when the
      rater also influenced treatment management and discharge. Our results do not
      support the proposition that specialized intake workers independent of those
      providing care would be able to predict LOS accurately.

PMID- 7649462
TI  - The role of loss in treatment outcomes of persistent somatization.
AB  - The present study examines the effect of loss on treatment outcome in 92
      persistently somatizing patients treated in an inpatient program. Patients were
      divided into one of three groups depending on the form of loss they experienced:
      early loss (loss of a parent before the age of 17, N = 25); recent loss
      (bereavement within the last 2 years, N = 21); or no loss (N = 46). The results
      indicate that patients experiencing an early loss had the poorest treatment
      outcome. The early loss group was characterized by poorer social adjustment prior
      to entry into the program compared with the recent loss group and a greater
      incidence of dependent personality disorder. The recent loss group showed the
      best outcome following treatment. The results support the concept that persistent
      somatization may arise from many precipitating factors. Assessing loss
      experiences in the patient may be an important factor in developing appropriate
      treatment strategies.

PMID- 7649463
TI  - Three-year follow-up and clinical implications of a mindfulness meditation-based
      stress reduction intervention in the treatment of anxiety disorders.
AB  - A previous study of 22 medical patients with DSM-III-R-defined anxiety disorders
      showed clinically and statistically significant improvements in subjective and
      objective symptoms of anxiety and panic following an 8-week outpatient physician
      referred group stress reduction intervention based on mindfulness meditation.
      Twenty subjects demonstrated significant reductions in Hamilton and Beck Anxiety
      and Depression scores postintervention and at 3-month follow-up. In this study, 3
      year follow-up data were obtained and analyzed on 18 of the original 22 subjects
      to probe long-term effects. Repeated measures analysis showed maintenance of the
      gains obtained in the original study on the Hamilton [F(2,32) = 13.22; p < 0.001]
      and Beck [F(2,32) = 9.83; p < 0.001] anxiety scales as well as on their
      respective depression scales, on the Hamilton panic score, the number and
      severity of panic attacks, and on the Mobility Index-Accompanied and the Fear
      Survey. A 3-year follow-up comparison of this cohort with a larger group of
      subjects from the intervention who had met criteria for screening for the
      original study suggests generalizability of the results obtained with the
      smaller, more intensively studied cohort. Ongoing compliance with the meditation
      practice was also demonstrated in the majority of subjects at 3 years. We
      conclude that an intensive but time-limited group stress reduction intervention
      based on mindfulness meditation can have long-term beneficial effects in the
      treatment of people diagnosed with anxiety disorders.

PMID- 7649464
TI  - Marital crises in oncology patients. An approach to initial intervention by
      primary clinicians.
AB  - Life-threatening illnesses such as cancer may precipitate marital crises in
      vulnerable relationships, and oncology clinicians often feel uncertain about how
      to approach them. This paper presents a framework for initial intervention based
      on the nature of the principal threat to the relationship. Immature relationships
      need distance and support for their identity as a couple; hostile dependent
      couples need to find consensus in order to structure communication; physically
      abusive relationships require monitoring in order to promote safety; and
      estranged couples need help in understanding their disappointment and identifying
      available support. Clinicians working in oncology can help couples in crisis by
      promoting a realistic balance of independence and dependence, clarifying the
      complexity of factors contributing to the crisis, considering referral for
      couples treatment, communicating with the team while respecting patients'
      confidences, and by choosing clear and compatible clinical roles. Primary
      clinicians can stabilize and treat marital crises, but need access to medically
      knowledgeable couples' therapists.

PMID- 7649465
TI  - Jumping from a general hospital.
AB  - Jumping is the most common reported means of suicide in general hospitals. There
      have been no published reviews of suicides of nonpsychiatric inpatients since
      1980. We describe 12 subjects who, between January 1980 and January 1992, jumped
      from a large general teaching hospital. Eight of them succumbed, providing a rate
      of suicide of 1.7 per 100,000 admissions. There were three clinical subgroups:
      those admitted after suicide attempts, the acutely delirious, and the chronically
      medically ill. Factors appearing frequently in the third subgroup were pain,
      dyspnea, transient confusion, poor prognosis, and recent adverse news. When we
      compared the hospital jumpers with 30 nonfatal jumpers who attended our Emergency
      Department, the medical and psychiatric profiles differed in the frequency of
      medical illnesses, advancing age, male gender, and absence of preexisting
      psychiatric illness. Proximity and ease of access to balconies and windows
      appeared to be highly relevant to the prevention of hospital jumping.

PMID- 7649466
TI  - The development of psychiatric medicine at Istanbul Faculty of Medicine and
      evaluation of 889 psychiatric referrals.
AB  - A clinical analysis of the psychiatric referrals (N = 889) during 1989-1991 is
      presented. The most prevalent psychiatric syndromes seen in both inpatients and
      outpatients are compared with reference to those areas of psychopathology that
      are less frequently identified by nonpsychiatrist physicians. The distribution of
      psychiatric referrals according to the various clinics in order of frequency was
      as follows: internal medicine, surgery, dermatology, and neurology. The most
      frequent reasons for consultation requests were (in order of frequency) the
      referring physician's difficulty in making a diagnosis; and patient anxiety,
      depression, adjustment problems, and past psychiatric illness in the history.
      Depressive illness was the most prevalent psychiatric disorder among both
      inpatient and outpatient referrals. However, the frequency of alcohol and
      substance abuse disorder in the inpatient population was only 3.17% and organic
      brain syndrome was the least frequently recognized psychiatric syndrome by the
      other clinicians. In this report, the clinical activities of the Liaison
      Psychiatry Unit of the Psychiatry Department in the Istanbul Medical Faculty are
      presented. The major problem areas and clinical training objectives of the
      Consultation-Liaison Psychiatry Unit are discussed.

PMID- 7649467
TI  - Severe ocular self-injury.
AB  - To further delineate the clinical characteristics of patients who deliberately,
      severely mutilate their eyes, we reviewed the medical records of a specialty eye
      hospital and found nine cases of intentional, severe, self-inflicted eye
      injuries. We identified two groups of patients. Most were young psychotic
      individuals with severe psychopathology often involving sexual and religious
      delusions, command hallucinations, and the propensity to act on delusions. The
      second group was comprised of patients with organic disabilities, either dementia
      or severe mental retardation, where a lack of impulse control and preexisting eye
      irritation or surgical operation may have contributed to the act. One patient was
      a recidivist. Two-thirds of the patients were confined at the time of the act.
      That self-mutilation may occur frequently in confined patients calls for active
      vigilance from caretakers; that it may recur calls for caution by the
      psychiatrist.

PMID- 7649468
TI  - Psychosocial care in the pediatric hospital. The need for scientific validation
      of clinical and cost effectiveness.
AB  - Emotional and social factors contribute to the outcome of medical treatment of
      pediatric patients with chronic illness, especially when associated with
      disability. They are also important in the management of psychosomatic illnesses,
      chronic pain syndromes, and specific chronic illnesses. In this era of
      preoccupation with the cost of health care, there is no consensus about the
      clinical necessity and cost effectiveness of pediatric hospital psychosocial care
      programs. The validity of psychosocial care as a clinically effective and cost
      effective approach to pediatric care, however, can be established only from
      carefully controlled, well-designed scientific studies. Optimally, these studies
      should be randomized, prospective, controlled trials that include the reliable
      identification of specific psychosocial problems and the subsequent validation of
      treatment approaches. Currently, such controlled studies of the effectiveness of
      pediatric hospital psychosocial care programs are lacking.

PMID- 7649469
TI  - 9-cis retinoic acid signaling: changing partners causes some excitement.

PMID- 7649470
TI  - Ste20-like protein kinases are required for normal localization of cell growth
      and for cytokinesis in budding yeast.
AB  - The yeast Ste20 protein kinase is involved in pheromone response. Mammalian
      homologs of Ste20 exist, but their function remains unknown. We identified a
      novel yeast STE20 homolog, CLA4, in a screen for mutations lethal in the absence
      of the G1 cyclins Cln1 and Cln2. Cla4 is involved in budding and cytokinesis and
      interacts with Cdc42, a GTPase required for polarized cell growth. Despite a
      cytokinesis defect, cla4 mutants are viable. However, double cla4 ste20 mutants
      cannot maintain septin rings at the bud neck and cannot undergo cytokinesis.
      Mutations in CDC12, which encodes one of the septins, were found in the same
      screen. Cla4 and Ste20 kinases apparently share a function in localizing cell
      growth with respect to the septin ring.

PMID- 7649471
TI  - Kip/Cip and Ink4 Cdk inhibitors cooperate to induce cell cycle arrest in response
      to TGF-beta.
AB  - G1 progression in mammalian cells requires the activity of the cyclin D-dependent
      kinases Cdk4 and/or Cdk6 and the cyclin E-dependent kinase Cdk2. Proliferating
      Mv1Lu mink lung epithelial cells and human keratinocytes contain high levels of
      the universal Cdk inhibitor p27Kip1 distributed in complexes with Cdk2, Cdk4, and
      Cdk6. Addition of the antimitogenic cytokine transforming growth factor-beta (TGF
      beta) elevates expression of the Cdk4/6-specific inhibitor p15Ink4B and induces
      the release of p27 from Cdk4 and Cdk6. In Mv1Lu cells, this release of p27
      coincides with increased binding of p27 to Cdk2. Recombinant p15 inhibits p27
      binding to Cdk4 in vitro, and p15 overexpression induces the transfer of p27 from
      Cdk4 to Cdk2 in vivo, suggesting that the release of Cdk4-bound p27 in TGF-beta
      treated cells is caused by the surge in p15 levels. In keratinocytes, TGF-beta
      increases not only p15 but also p21Cip1, which binds to Cdk2. These events
      correlate with Cdk2 inhibition and cell cycle arrest and occur without a loss of
      G1 Cdk components. The results suggest that TGF-beta induces G1 arrest in these
      two epithelial cell types by inhibiting various cyclin-Cdk kinases through the
      cooperative action of an Ink4 Cdk inhibitor and a Cip/Kip Cdk inhibitor.
      Subsequent to cell cycle arrest, Cdk2 and Cdk4 levels decline as part of a second
      set of events that may represent a program of cell adaptation to the quiescent
      state.

PMID- 7649472
TI  - Apoptotic phenotype induced by overexpression of wild-type gas3/PMP22: its
      relation to the demyelinating peripheral neuropathy CMT1A.
AB  - Although the Gas3/PMP22 protein is expressed at highest levels in differentiated
      Schwann cells, its presence, albeit at lower levels, in non-neuronal tissues and
      in NIH-3T3 growth-arrested fibroblasts argues for a more general function of this
      protein that is uncoupled to myelin structure. We show that gas3/PMP22
      overexpression in NIH-3T3 growing cells leads to an apoptotic-like phenotype,
      which is suppressed by antioxidants and characterized by typical membrane
      blebbing, rounding up, and chromatin condensation, but with no evidence of DNA
      fragmentation. REF-52 fibroblasts seem to be completely refractive to gas3/PMP22
      overexpression. Recently, several point mutations of the human gas3/PMP22 gene
      have been associated with Charcot-Marie-Tooth type 1A (CMT1A), a common
      hereditary demyelinating neuropathy. When gas3/PMP22 point mutations (L16P, S79C,
      T118M, and G150D) are similarly overexpressed in NIH-3T3 cells, the induced
      apoptotic-like phenotype as compared to the wild-type is significantly reduced.
      Both of the dominant mutations (L16P, S79C) for CMT1A behave as dominant
      negatives with respect to the wild type, whereas T118M, the only recessive mutant
      described, behaves as recessive under the same coexpression experiments. These
      data suggest a role for altered Schwann cell apoptosis in the pathogenesis of
      CMT1A.

PMID- 7649473
TI  - Biallelic expression of imprinted genes in the mouse germ line: implications for
      erasure, establishment, and mechanisms of genomic imprinting.
AB  - Genomic imprinting in mammals determines parental-specific (monoallelic)
      expression of a relatively small number of genes during development. Imprinting
      must logically be imparted in the germ line, where inherited maternal and
      paternal imprinting is erased and new imprinting established according to the
      individual's sex. We have assessed the allele-specific expression of four
      imprinted genes, two of which exhibit maternal-specific (H19 and Igf2r) and two
      of which exhibit paternal-specific (Igf2 and Snrpn) monoallelic somatic
      expression, in the germ line of F1 hybrid mice utilizing quantitative RT-PCR
      single-nucleotide primer extension assays. The expression of each gene was
      biallelic in the female and male germ line from the time that migratory mitotic
      PGCs entered the embryonic genital ridge and throughout gametogenesis, except
      that H19 RNA was not detected late in gametogenesis. These findings demonstrate
      that inherited imprinting is erased, or not recognized, in germ cells by the time
      of genital ridge colonization; also that new imprinting may not be established
      until late in gametogenesis, or that it is incomplete or not recognized at this
      stage. Regardless of imprinting status, a generalized neutralization of
      imprinting is evident in the germ line, associated with the totipotent state of
      this unique cell lineage.

PMID- 7649474
TI  - Cis-regulation of achaete and scute: shared enhancer-like elements drive their
      coexpression in proneural clusters of the imaginal discs.
AB  - The pattern of bristles and other sensory organs on the adult cuticle of
      Drosophila is prefigured in the imaginal discs by the pattern of expression of
      the proneural achaete (ac) and scute (sc) genes, two members of the ac-sc complex
      (AS-C). These genes are simultaneously expressed by groups of cells (the
      proneural clusters) located at constant positions in discs. Their products
      (transcription factors of the basic-helix-loop-helix family) allow cells to
      become sensory organ mother cells (SMCs), a fate normally realized by only one or
      a few cells per cluster. Here we show that the highly complex pattern of
      proneural clusters is constructed piecemeal, by the action on ac and sc of site
      specific, enhancer-like elements distributed along most of the AS-C
      (approximately 90 kb). Fragments of AS-C DNA containing these enhancers drive
      reporter lacZ genes in only one or a few proneural clusters. This expression is
      independent of the ac and sc endogenous genes, indicating that the enhancers
      respond to local combinations of factors (prepattern). We show further that the
      cross-activation between ac and sc, discovered by means of transgenes containing
      either ac or sc promoter fragments linked to lacZ and thought to explain the
      almost identical patterns of ac and sc expression, does not occur detectably
      between the endogenous ac and sc genes in most proneural clusters. Our data
      indicate that coexpression is accomplished by activation of both ac and sc by the
      same set of position-specific enhancers.

PMID- 7649476
TI  - Nucleosome positioning on the MMTV LTR results from the frequency-biased
      occupancy of multiple frames.
AB  - The translational positions of nucleosomes in the promoter region of the mouse
      mammary tumor virus (MMTV) were defined at high resolution. Nucleosome boundaries
      were determined in primer extension assays using full-length single-stranded
      mononucleosomal DNA prepared from cells treated with formaldehyde, a reversible
      protein-DNA cross-linking agent. Multiple boundaries were observed in both the
      nucleosome A (Nuc-A) and Nuc-B region of the promoter, indicating multiple
      nucleosome translational frames. The different nucleosome frames in both the Nuc
      A and Nuc-B regions were occupied unequally. The most frequently occupied frames
      were found clustered within 50-60 bases of each other, resulting in a
      distribution centered in the positions defined previously at low resolution for
      Nuc-A and Nuc-B. The most abundant 5' ends of the frames in the B region were
      found between -235 and -187, and the 3' ends between -86 and -36, whereas in the
      A region the most abundant 5' ends were between -22 and +42, and the 3' ends
      between +121 and +186. Although frames in the Nuc-B region of the LTR extend at a
      low frequency in the 5' direction toward the Nuc-C region, there is a sharp
      discontinuity in the 3' direction toward Nuc-A, suggesting the presence of a
      boundary constraint in the A-B linker. The positions and relative occupancies of
      nucleosome frames, in either the B or the A region, did not change when the
      promoter was activated with dexamethasone.

PMID- 7649475
TI  - MATa donor preference in yeast mating-type switching: activation of a large
      chromosomal region for recombination.
AB  - During mating-type gene switching in Saccharomyces cerevisiae, DNA at the MAT
      locus is replaced by sequences copied from one of two unexpressed donor loci, HML
      or HMR, located near the two ends of the same chromosome and > or = 90 kb from
      MAT. MATa cells recombine nearly 90% of the time with HML, whereas MAT alpha
      cells select HMR. MATa donor preference was examined by deleting HML and
      inserting a donor at other chromosome III locations. MATa activated a large (> or
      = 40 kb) region near the left end of chromosome III, such that a donor placed at
      several sites within this domain was strongly preferred over HMR. When inserted
      outside of this domain, the donor was used equally with HMR. MATa donor
      preference for HML was abolished by the expression of the negative regulator, MAT
      alpha 2; however, HML regained its preferred status when the donor was
      unsilenced. Mating-type-dependent activation of the left end of the chromosome is
      also observed for other types of recombination that do not involve MAT switching.
      Spontaneous recombination between two leu2 alleles is 20-30 times higher in MATa
      than in MAT alpha when one of the leu2 alleles is inserted in place of HML.
      Transcription in this donor activation region is not affected by mating type. We
      conclude that MATa donor preference involves a mating-type-regulated change in
      the accessibility of a large chromosomal domain for recombination.

PMID- 7649477
TI  - Rapid induction of heparin-binding epidermal growth factor/diphtheria toxin
      receptor expression by Raf and Ras oncogenes.
AB  - We have used differential display PCR to search for mRNAs induced by delta Raf
      1:ER, an estradiol-dependent form of Raf-1 kinase. Through this approach the gene
      encoding heparin-binding epidermal growth factor (HB-EGF) was identified as an
      immediate-early transcriptional target of oncogenic Raf kinases. Activation of
      delta Raf-1:ER and a conditional oncogenic form of B-Raf, delta B-RAF:ER,
      resulted in rapid and sustained induction of HB-EGF mRNA expression and secretion
      of mature HB-EGF from cells. Neutralizing anti-HB-EGF antisera prevented the
      delayed activation of the c-Jun amino-terminal kinases that is observed in cells
      transformed by delta Raf-1:ER. These results demonstrate that distinct signaling
      pathways can cross talk via the secretion of polypeptide growth factors.
      Furthermore, cells transformed by oncogenic Ras, which also induced HB-EGF
      expression, demonstrated a marked increase in sensitivity to the cytotoxic action
      of diphtheria toxin, for which the membrane anchored HB-EGF precursor acts as a
      cell-surface receptor.

PMID- 7649478
TI  - Mice lacking the c-rel proto-oncogene exhibit defects in lymphocyte
      proliferation, humoral immunity, and interleukin-2 expression.
AB  - The c-rel proto-oncogene, which is expressed predominantly in hemopoietic cells
      encodes a subunit of the NF-kappa B-like family of transcription factors. In mice
      with an inactivated c-rel gene, whereas development of cells from all hemopoietic
      lineages appeared normal, humoral immunity was impaired and mature B and T cells
      were found to be unresponsive to most mitogenic stimuli. Phorbol ester and
      calcium ionophore costimulation, in contrast to certain membrane receptor
      mediated signals, overcame the T cell-proliferative defect, demonstrating that T
      cell proliferation occurs by Rel-dependent and -independent mechanisms. The
      ability of exogenous interleukin-2 to restore T Cell, but not B cell,
      proliferation indicates that Rel regulates the expression of different genes in B
      and T cells that are crucial for cell division and immune function.

PMID- 7649479
TI  - HMG17 is a chromatin-specific transcriptional coactivator that increases the
      efficiency of transcription initiation.
AB  - We have examined the effect of HMG17 on transcription by RNA polymerase II by the
      assembly and analysis of HMG17-containing chromatin templates consisting of
      regularly spaced nucleosomal arrays. Structural analysis of the chromatin
      indicated that HMG17 is incorporated into chromatin in a physiological manner
      with the full complement of core histones. The transcriptional studies revealed
      that HMG17 stimulates transcription in conjunction with the sequence-specific
      activator GAL4-VP16. This effect was observed with chromatin, but not with non
      nucleosomal templates, and required the presence of HMG17 during chromatin
      assembly. The incorporation of HMG17 into chromatin resulted in a 7- to 40-fold
      stimulation of GAL4-VP16-activated transcription to levels that were comparable
      to those observed with histone-free DNA templates. In contrast, transcription
      from HMG17-containing chromatin was not detectable in the absence of GAL4-VP16 or
      with a GAL4 derivative [GAL4(1-147)] lacking the VP16 activation domain. Finally,
      the incorporation of HMG17 into chromatin was found to increase the efficiency of
      transcription initiation, but not the extent of transcriptional elongation. Thus,
      HMG17 is a chromatin-specific transcriptional coactivator that increases the
      efficiency of initiation of transcription by RNA polymerase II.

PMID- 7649480
TI  - Pit-1 binding to specific DNA sites as a monomer or dimer determines gene
      specific use of a tyrosine-dependent synergy domain.
AB  - Transcriptional activation of the prolactin and growth hormone genes, occurring
      in a cell-specific fashion, requires short-range synergistic interactions between
      the pituitary-specific POU domain factor Pit-1 and other transcription factors,
      particularly nuclear receptors. Unexpectedly, we find that these events involve
      the gene-specific use of alternative Pit-1 synergy domains. Synergistic
      activation of the prolactin gene by Pit-1 and the estrogen receptor requires a
      Pit-1 amino-terminal 25-amino-acid domain that is not required for analogous
      synergistic activation of the growth hormone promoter. The action of this Pit-1
      synergy domain is dependent on the presence of two of three tyrosine residues
      spaced by 6 amino acids and can be replaced by a comparable tyrosine-dependent
      trans-activation domain of an unrelated transcription factor (hLEF). The gene
      specific utilization of this tyrosine-dependent synergy domain is conferred by
      specific Pit-1 DNA-binding sites that determine whether Pit-1 binds as a monomer
      or a dimer. Thus, the critical DNA site in the prolactin enhancer, where this
      domain is required, binds Pit-1 as a monomer, whereas the Pit-1 sites in the
      growth hormone gene, which do not utilize this synergy domain, bind Pit-1 as a
      dimer. The finding that the sequence of specific DNA sites dictates alternative
      Pit-1 synergy domain utilization based on monomeric or dimeric binding suggests
      an additional regulatory strategy for differential target gene activation in
      distinct cell types.

PMID- 7649481
TI  - Resolution of spontaneous bleeding events but failure of pregnancy in fibrinogen
      deficient mice.
AB  - To explore the role of the key coagulation factor, fibrinogen, in development,
      hemostasis, wound repair, and disease pathogenesis, we disrupted the fibrinogen A
      alpha chain gene in mice. Homozygous, A alpha chain-deficient (A alpha-/-) mice
      are born normal in appearance, and there is no evidence of fetal loss of these
      animals based on the Mendelian pattern of transmission of the mutant A alpha
      chain allele. All of the component chains of fibrinogen (A alpha, B beta, and
      gamma) are immunologically undetectable in the circulation of both neonatal and
      adult A alpha-/- mice, and blood samples fail to either clot or support platelet
      aggregation in vitro. Overt bleeding events develop shortly after birth in
      approximately 30% of A alpha-/- mice, most frequently in the peritoneal cavity,
      skin, and soft tissues around joints. Remarkably, most newborns displaying signs
      of bleeding ultimately control the loss of blood, clear the affected tissues, and
      survive the neonatal period. Juveniles and young adult A alpha-/- mice are
      predisposed to spontaneous fatal abdominal hemorrhage, but long-term survival is
      variable and highly dependent on genetic background. The periodic rupture of
      ovarian follicles in breeding-age A alpha-/- females does not appear to
      significantly diminish life expectancy relative to males; however, pregnancy
      uniformly results in fatal uterine bleeding around the tenth day of gestation.
      Microscopic analysis of spontaneous lesions found in A alpha-/- mice suggests
      that fibrin(ogen) plays a fundamental role in the organization of cells at sites
      of injury.

PMID- 7649482
TI  - The bacterial enhancer-binding protein NTRC is a molecular machine: ATP
      hydrolysis is coupled to transcriptional activation.
AB  - NTRC is a prokaryotic enhancer-binding protein that activates transcription by
      sigma 54-holoenzyme. NTRC has an ATPase activity that is required for
      transcriptional activation, specifically for isomerization of closed complexes
      between sigma 54-holoenzyme and a promoter to open complexes. In the absence of
      ATP hydrolysis, there is known to be a kinetic barrier to open complex formation
      (i.e., the reaction proceeds so slowly that the polymerase synthesizes
      essentially no transcripts even from a supercoiled template). We show here that
      open complex formation is also thermodynamically unfavorable. In the absence of
      ATP hydrolysis the position of equilibrium between closed and open complexes
      favors the closed ones. Use of linear templates with a region of heteroduplex
      around the transcriptional start site--"preopened" templates--does not bypass the
      requirement for either NTRC or ATP hydrolysis, providing evidence that the rate
      limiting step in open complex formation does not lie in DNA strand denaturation
      per se. These results are in contrast to recent findings regarding the ATP
      requirement for initiation of transcription by eukaryotic RNA polymerase II; in
      the latter case, the ATP requirement is circumvented by use of a supercoiled
      plasmid template or a preopened linear template.

PMID- 7649483
TI  - Asymmetry in active complexes of FLP recombinase.
AB  - The FLP recombinase promotes a site-specific recombination reaction in the 2mu
      plasmid of yeast. The protein-DNA complex that carries out the reaction is
      asymmetric. Three FLP monomers bound to specific FLP-recognition sequences are
      required to efficiently carry out one set of reciprocal DNA cleavage and strand
      exchange events on a Holliday junction substrate. If a fourth monomer plays an
      auxiliary role in the reaction, it is bound without sequence specificity. The
      data suggest a modified model for cleavage of DNA in trans by the FLP recombinase
      that might help reconcile some seemingly conflicting resulted obtained with
      integrase class recombinases.

PMID- 7649484
TI  - Epigenetic self-regulation of developmental excision of an internal eliminated
      sequence on Paramecium tetraurelia.
AB  - Differentiation of the somatic macronucleus of ciliates after sexual events
      involves the programmed excision of thousands of single-copy internal eliminated
      sequences (IESs) from the germ-line genome. We have studied two cell lines of
      Paramecium tetraurelia that have identical germ-line genomes but differ in their
      macronuclear genomes. In the IES- cell line, a 222-bp IES interrupting a coding
      sequence is reproducibly excised during macronuclear differentiation, whereas it
      is not in the IES+ cell line. In a cross between the two lines, the developmental
      alternative in maternally inherited, suggesting that it is epigenetically
      controlled by the old (prezygotic) macronucleus in each cell. Transformation of
      the macronucleus of both lines with plasmids carrying fragments of either version
      of the gene shows that the presence of the IES sequence in the old macronucleus
      results in retention of the IES in the new macronuclear genome of sexual progeny.
      This could be attributable to (1) inhibition of excision, or (2) repair of a
      double-strand gap left in the genomic sequence after constitutive excision of the
      IES, by a polymerization mechanism using a homologous IES+ template from the old
      macronucleus. The latter possibility is ruled out by experiments showing that
      modified IESs can inhibit excision without being copied in the new macronuclear
      genome. Possible mechanisms are discussed in the light of a quantitative analysis
      of excision inhibition by the maternal IES sequence.

PMID- 7649485
TI  - Hypochlorite induces lipid peroxidation in blood lipoproteins and phospholipid
      liposomes.
AB  - The accumulation of lipid peroxidation products reacting with 2-thiobarbituric
      acid (TBARS) has been observed both in very low density blood lipoprotein (VLDL)
      and suspensions of liposomes prepared from VLDL phospholipids incubated with
      hypochlorite. Butylated hydroxytoluene (BHT) completely inhibited TBARS formation
      at a concentration of 100 microM, at which it decreased the concentration of
      hypochlorite in the absence of liposomes only by 7%. The formation of lipid
      peroxidation products in course of the incubation of egg yolk phospholipid
      liposomes with hypochlorite has been revealed using three methods: (1)
      measurement of TBARS, (2) measurement of additional amounts of TBARS resulting
      from the introduction of excess Fe2+ to peroxidized liposomes (delta TBARS), and
      (3) measurement of the chemiluminescence flash amplitude appeared upon the
      addition of Fe2+ to the suspension. The results obtained by all these methods
      were similar: Lipid peroxidation products were accumulated during the first 2 to
      3 h of liposome incubation with 100 microM hypochlorite, and the amount of lipid
      peroxidation products accumulated after incubation was directly proportional to
      the initial hypochlorite concentration. These data suggest that hypochlorite can
      initiate lipid peroxidation both in lipoproteins and phospholipid liposomes.

PMID- 7649486
TI  - Gas chromatographic differentiation between myeloperoxidase activity and Fenton
      type oxidants.
AB  - Several pathological situations are characterized by the production of reactive
      oxygen species (ROS), whereby different sources such as activated leukocytes and
      xanthine oxidase seem to be mainly responsible. The contribution of immigrating
      activated neutrophils to symptom development during inflammatory processes or
      after reperfusion of ischemic tissues is a matter of continuing discussion. We
      present a simple method for the differentiation between oxygen activating
      reactions in which neutrophil-derived myeloperoxidase is involved. The method is
      based on the gas chromatographic detection of ethylene, which is formed by the
      reaction of alpha-keto-gamma-methylthiobutyric acid (KMB) or 1-amino-cyclopropane
      1-carboxylic acid (ACC) with ROS. In the presence of OH-radical-type oxidants,
      only KMB yields ethylene whereas ACC is fragmented by myeloperoxidase-derived
      species (OCl-, chloramines). The amounts of ethylene may be used as an indicator
      for the relative contribution of Fenton-type or myeloperoxidase-catalyzed
      reactions.

PMID- 7649487
TI  - Detection of free radicals in aqueous extracts of cigarette tar by electron spin
      resonance.
AB  - Aqueous extracts of cigarette tar (ACT) autooxidize to produce semiquinone,
      hydroxyl, and superoxide radicals in air-saturated buffered aqueous solutions.
      The semiquinone species were detected by direct electron spin resonance (ESR)
      measurements and identified as o- and p-benzosemiquinone radicals by comparison
      with the ESR signals of catechol and hydroquinone radicals under similar
      conditions. The rate of formation of these radicals was dependent on pH. Hydroxyl
      and superoxide radicals were detected as 5,5-dimethyl-1-pyrroline-N-oxide (DMPO)
      spin adducts by ESR spin trapping. Superoxide dismutase (SOD) (20 units/ml)
      inhibited the formation of the superoxide spin adduct of DMPO completely.
      Addition of Fe2+ to this system increased the ESR signal intensity of hydroxyl
      radical spin adduct of DMPO three to five times. These results indicate that
      superoxide and hydroxyl radicals are produced during the autooxidation of
      hydroquinone- and catechol-related species in ACT.

PMID- 7649488
TI  - Acetaminophen-induced hepatic injury in mice: the role of lipid peroxidation and
      effects of pretreatment with coenzyme Q10 and alpha-tocopherol.
AB  - This study was performed to determine whether oxidative stress contributed to the
      initiation or progression of hepatic injury produced by acetaminophen (APAP).
      Treatment of fasted mice with APAP (400 mg/kg, I.P.) led to hepatic injury as
      indicated by a marked elevation of plasma alanine aminotransferase (ALT). APAP
      caused an increased amount of thiobarbituric acid-reactive substance (TBARS),
      which was accompanied by a loss of reduced forms of coenzyme Q9 (CoQ9H2) and
      coenzyme Q10 (CoQ10H2) functioning as antioxidants. APAP also markedly decreased
      hepatic reduced glutathione (GSH) levels. Pretreatment with CoQ10 (5 mg/kg, I.V.)
      reduced hepatic TBARS levels to 30% and plasma ALT levels to 26% of placebo
      pretreatment levels without affecting hepatic GSH levels at 3 h of APAP
      treatment. alpha-Tocopherol (alpha-Toc) (20 mg/kg, I.V.) pretreatment also
      reduced hepatic TBARS levels to 13% and plasma ALT levels to 27% of placebo
      pretreatment levels without affecting hepatic GSH levels. These results suggest
      that oxidative stress followed by lipid peroxidation might play a role in the
      pathogenesis of APAP-induced hepatic injury, and pretreatment with lipid-soluble
      antioxidants such as CoQ10 and alpha-Toc can limit hepatic injury produced by
      APAP.

PMID- 7649489
TI  - alpha-Tocopherol and trolox block the early intracellular events (TBARS and
      calcium rises) elicited by oxidized low density lipoproteins in cultured
      endothelial cells.
AB  - Low-density lipoproteins (LDLs), treated by UV-C radiations under conditions
      permitting mildly oxidized LDL (6 +/- 2 nmol TBARS/mg apoB, without major
      structural or functional alteration of apoB), have been used for studying their
      cytotoxicity to cultured bovine aortic endothelial cells and the cytoprotective
      effect of various analogs of alpha-tocopherol. Toxic doses of oxidized LDL evoked
      intracellular events, such as cellular thiobarbituric acid reactive substances
      (TBARS) and a sustained peak of [Ca2+]i (cytosolic calcium). The sustained
      [Ca2+]i peak seems to be directly involved in the genesis of cell injury leading
      to cell death in contrast to cellular TBARS, which seems to be either an earlier
      step of signal transduction or a side effect, as shown by inhibiting the [Ca2+]i
      rise by ethylene glycol-O,O'-bis(amino ethyl)-N1N1N'1N'-tetraacetic acid (EGTA)
      added just before the time of the [Ca2+]i peak. When alpha-tocopherol or trolox
      (a short-chain, water-soluble analog of alpha-tocopherol) were added to the
      culture medium simultaneously with oxidized LDL, they were able to increase the
      resistance of endothelial cells against the cytotoxic effect of oxidized LDL,
      whereas alpha-tocopheryl acetate and alpha-tocopheryl succinate were almost
      completely ineffective because of the liberation of only very low levels of alpha
      tocopherol. Trolox exhibited a more potent cytoprotective effect than alpha
      tocopherol (IC50: 1 +/- 0.2 and 8 +/- 2 mumol/l for trolox and alpha-tocopherol,
      respectively). As shown by preincubating cells with effective concentrations of
      alpha-tocopherol or trolox, the cytoprotective effect was completely independent
      of any inhibition of LDL oxidation and was remanent for 2 d with alpha-tocopherol
      or for 3-4 d with trolox. Cytoprotective concentrations of trolox and alpha
      tocopherol did not inhibit LDL uptake but acted at the cellular level by blocking
      the formation of cellular TBARS and the sustained [Ca2+]i peak as well. The
      potential relevance of these data in relation to the prevention of
      atherosclerosis is discussed.

PMID- 7649490
TI  - Photoinduction of strand scission in DNA by uric acid and Cu(II)
AB  - Uric acid (2,6,8-trioxo purine) is produced in mammalian systems as an end
      product of purine metabolism and has been proposed as a natural, physiological
      antioxidant. In the presence of Cu(II) and molecular oxygen, uric acid caused
      breakage of calf thymus DNA and supercoiled plasmid DNA. Such breakage was
      considerably enhanced in the presence of visible light. The DNA cleavage did not
      appear to have any preferred site(s) or sequence(s) for strand scission. Uric
      acid catalyzed the reduction of Cu(II) to Cu(I), which was shown to be an
      essential intermediate in the DNA cleavage reaction. Uric acid also reduced
      oxygen to superoxide, and hydroxyl radicals were formed in the presence of
      Cu(II). The involvement of active oxygen species in the reaction was established
      by the inhibition of DNA breakage by known scavengers of oxygen radicals.

PMID- 7649491
TI  - Is alpha-tocopherol a reservoir for alpha-tocopheryl hydroquinone?
AB  - The products of oxidation of the alpha-tocopherol model compound, 2,2,5,7,8
      pentamethyl-6-chromanol (PH) by t-butyl hydroperoxide in chloroform varied with
      the amount of water present. In the presence of a trace of water, the main
      products were the spirodimer (PSD) and spirotrimer (PST). As the content of water
      increased, the main product became 2-(3-hydroxy-3-methylbutyl)-3,5,6-trimethyl
      1,4-benzoquinone (PQ). Oxidation of PH in aqueous liposome suspension also
      produced PQ as the major product. These results suggested that, in aqueous
      solutions, the major oxidation product of PH would be PQ and of alpha-tocopherol
      (TH) would be alpha-tocopheryl quinone (TQ). The ease of reduction of PQ and TQ
      was studied in chemical and biological systems. PQ, TQ, and ubiquinone-10 (UQ)
      were rapidly reduced to their respective hydroquinones (PQH2, TQH2, and UQH2) at
      pH 7.3 by NADH plus FAD. Whole blood reduced PQ rapidly at 37 degrees C to PQH2
      but did not reduce TQ to TQH2. Human peripheral blood mononuclear cells took up
      TQ from a bovine serum albumin complex and reduced it to TQH2. Ingestion of TQ
      (350 mg) by one of us (PSK) resulted in the formation of TQH2 during a 5 h
      period. These results demonstrate that several biological systems are able to
      reduce TQ to TQH2 and that it is a reaction that may occur normally in vivo.

PMID- 7649492
TI  - Differential sensitivity to hydrogen peroxide of dopaminergic and noradrenergic
      neurotransmission in rat brain slices.
AB  - Oxidative stress, induced by hydrogen peroxide, has been implicated in the
      pathogenesis of Parkinson's disease. Only scarce information is available if and
      how hydrogen peroxide, a side product of catecholamine (CA) breakdown, interferes
      with CAergic neurotransmission. Therefore, we investigated the effect of hydrogen
      peroxide on the release of [3H]dopamine (DA) and [3H]noradrenaline (NA) from rat
      striatal and cortical tissue slices, respectively. Hydrogen peroxide (0.01-1 mM)
      stimulated the spontaneous release of [3H]DA from striatal slices. Its effect on
      [3H]NA release from cortical slices, however, was much smaller than on DA release
      and occurred only in concentrations above 0.1 mM. Furthermore, only in
      concentrations of 1 mM or higher did a stimulation of spontaneous release of
      radioactivity from striatal slices incubated with [3H]choline occur. Omission of
      calcium significantly enhanced the effect on DA release, and an increase of
      calcium significantly reduced it. Blockade of vesicular storage with reserpine
      (0.3 microM) almost completely abolished [3H]DA release induced by hydrogen
      peroxide. Following incubation of striatal slices with [3H]NA in the presence of
      the NA (re)uptake blocker desmethylimipramine (0.3 microM), NA release was
      observed at a concentration (0.1 mM) at which no effect occurred in cortical
      slices. Moreover, under these conditions [3]NA and [3H]DA release from striatal
      slices reached comparable levels. Our results show that hydrogen peroxide induces
      a nonexocytotic release of DA and NA by interfering with the vesicular uptake
      and/or storage of these CAs. However, the striatal DA storage system,
      irrespective of the presence of either DA or NA, appeared to be substantially
      more sensitive to this effect than its cortical equivalent for storage of NA.

PMID- 7649493
TI  - Detection by ESR of DMPO hydroxyl adduct formation from islets of Langerhans.
AB  - Electron spin resonance (ESR) spectroscopy together with spin trapping techniques
      and the application of state-of-the-art loop gap resonators was used to provide a
      direct measure of spontaneous oxygen radical production by homogenates of freshly
      isolated and cultured rat pancreatic islets. Using the spin trap agent, 5,5
      dimethyl-1-pyrroline-N-oxide (DMPO), we were able to detect production by islets
      of an ESR-sensitive radical signal consisting of a quartet with intensity ratio
      of 1:2:2:1 and hyperfine splitting of aN = aH = 14.9 Gauss, which is consistent
      with the DMPO-OH adduct. The amplitude of the signal was decreased by decreasing
      amount of islets and not detected in the absence of islets. Formation of the DMPO
      OH adduct was diminished by the hydroxyl radical scavengers (e.g., ethanol,
      dimethylsulfoxide, and dimethylthiourea). Only partial attenuation of signal was
      produced by incubation with an iron chelator or using chelex-treated buffers. The
      ESR signal was insensitive to the xanthine oxidase inhibitor, oxypurinol, or to
      superoxide dismutase, but was eliminated in a concentration-dependent manner by
      either potassium cyanide or catalase (but not heat-inactivated catalase). These
      observations suggest that the origin of the DMPO-OH arose not from free hydroxyl
      radicals but primarily from endogenous hydrogen peroxide production perhaps of
      mitochondrial origin. The development of this technology has implications for the
      potential measure of oxygen radical production in islet homogenates under
      pathologic conditions as well as to the application of other cell culture
      systems.

PMID- 7649494
TI  - alpha-Lipoic acid as a biological antioxidant.
AB  - alpha-Lipoic acid, which plays an essential role in mitochondrial dehydrogenase
      reactions, has recently gained considerable attention as an antioxidant. Lipoate,
      or its reduced form, dihydrolipoate, reacts with reactive oxygen species such as
      superoxide radicals, hydroxyl radicals, hypochlorous acid, peroxyl radicals, and
      singlet oxygen. It also protects membranes by interacting with vitamin C and
      glutathione, which may in turn recycle vitamin E. In addition to its antioxidant
      activities, dihydrolipoate may exert prooxidant actions through reduction of
      iron. alpha-Lipoic acid administration has been shown to be beneficial in a
      number of oxidative stress models such as ischemia-reperfusion injury, diabetes
      (both alpha-lipoic acid and dihydrolipoic acid exhibit hydrophobic binding to
      proteins such as albumin, which can prevent glycation reactions), cataract
      formation, HIV activation, neurodegeneration, and radiation injury. Furthermore,
      lipoate can function as a redox regulator of proteins such as myoglobin,
      prolactin, thioredoxin and NF-kappa B transcription factor. We review the
      properties of lipoate in terms of (1) reactions with reactive oxygen species; (2)
      interactions with other antioxidants; (3) beneficial effects in oxidative stress
      models or clinical conditions.

PMID- 7649495
TI  - Reduction of reperfusion injury of human myocardium by allopurinol: a clinical
      study.
AB  - To determine the possibility of myocardial protection against reperfusion injury
      by allopurinol, 22 aortocoronary bypass patients were studied. Eight patients
      received allopurinol (200 mg during induction of anesthesia and 100 mg after
      starting extracorporeal circulation) during surgery (group B), and 14 patients
      served as a control (group A). Blood samples and myocardial biopsies were taken
      before and 10 min after aortic cross-clamping. No statistically significant
      difference between the two groups was observed considering gender, age, prior
      myocardial infarction, left ventricular end diastolic pressure (LVEDP), and
      aortic cross-clamp time. Preservation of cardiac tissue was assessed by the
      measurement of quantitative birefringence (QBR) changes upon the addition of
      adenosine 5'-triphosphate (ATP) plus calcium in biopsies and the need for
      postoperative inotropes. The synthesis of peroxides was estimated by the
      measurement of leukotriene B4 and C4 (LTB4, LTC4). LTB4 was below the level of
      detection (< 1.5 ng/l) before and after cross-clamping in both groups, while the
      LTC4 level for group A increased from < 1.5 to 27 +/- 17 ng/l compared to an
      increase of < 1.5 to 11 +/- 8 ng/l for group B after 10 min of reperfusion (p =
      .036). The decrease in QBR value in group A was 1.26 +/- 0.28 and 0.35 +/- 0.23
      for group B (p < .003). Postoperatively, 11 out of 14 patients in group A needed
      inotropic support (dopamine or dobutamine), whereas two patients out of eight did
      so in group B.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7649497
TI  - Handedness in musicians.
AB  - In order to study the prevalence of left- or mixed-handedness in musicians, we
      decided to examine a population of professional musicians. We assessed the
      handedness pattern of 382 members of 7 orchestras. The prevalence of non-right
      handedness in musicians was found to be much the same as in the general
      population. Similar results emerged from a study of young music school pupils. We
      conclude that brain structural tomographic imaging should ideally be performed,
      and the pattern of cerebral asymmetry analysed in order to assess cerebral
      lateralization in musicians.

PMID- 7649496
TI  - Effect of systemic dexamethasone on extracellular amino acids, GABA and
      acetylcholine release in rat hippocampus using in vivo microdialysis.
AB  - In order to elucidate the mechanism of the cytotoxic effect of glucocorticoid on
      the rat hippocampus, we studied the effects of dexamethasone, a synthetic
      glucocorticoid, on neurotransmitter release from the hippocampus by in vivo
      microdialysis. Dexamethasone (10 mg/kg) was administered i.p. and the
      extracellular concentrations of the amino acids (glutamate, aspartate, glycine),
      GABA and acetylcholine were determined in the hippocampus of freely moving rats.
      Glutamate concentration increased by 20-25% after dexamethasone administration
      and this effect continued for 1 hour. The extracellular concentration of the
      other neurotransmitters, however, did not show any significant changes. From
      these results, we concluded that increased extracellular glutamate may be
      involved, at least in part, in the cytotoxic effect of glucocorticoid on
      hippocampal neurons.

PMID- 7649498
TI  - Cyclandelate versus propranolol in the prophylaxis of migraine--a double-blind
      placebo-controlled study.
AB  - The aim of the present study was to ascertain the comparative efficacy of
      cyclandelate, a migraine prophylactic with calcium overload blocking properties,
      versus propranolol, a non-selective beta-adrenergic blocker, and placebo. Based
      on different statistical analysis procedures (including time series analysis) a
      responder and nonresponder evaluation for cyclandelate and propranolol was
      performed. In addition, an attempt was made to identify the dose relationship of
      the various drugs on headache parameters. In a double-blind placebo-controlled
      study 84 patients were treated in a placebo run-in phase (4 weeks). The patients
      were then randomized by the statistical criterion of placebo responder and
      nonresponder to either the cyclandelate or the propranolol group. The total
      treatment period included a low-dosage phase (8 weeks) and high-dosage phase (8
      weeks). All patients kept a headache diary before, during and after treatment.
      The data were assessed by time series analysis (ARIMA), as well as by analysis of
      variance and nonparametric statistics. Based on ARIMA statistics, 39.3% of the
      patients showed a significant improvement of migraine during treatment with
      cyclandelate compared with 29.4% placed on propranolol. Higher doses of
      cyclandelate and propranolol were more effective. Using the qualitative response
      criterion of a 50% reduction in migraine symptoms, cyclandelate showed a response
      in 67.9% and propranolol in 41.2% of all cases. It can therefore be concluded
      that cyclandelate as well as propranolol are two comparable substances in the
      prophylactic treatment of migraine, with cyclandelate showing fewer side effects.

PMID- 7649499
TI  - Multiparametric quantitative evaluation of the speech production system: a study
      in normal subjects.
AB  - This paper describes a systems architecture developed for the study of the speech
      production system. The architecture utilizes two personal computers: the "Word
      Image Presenter" (WIP) that presents a sequence of words to the subject under
      examination as visual stimulation, and the "Signal Acquisition System" that
      controls the WIP, acquires the acoustic signal, the oromandibular
      electromyographic signals, the kinematic lip and jaw signals and measures
      reaction times and durations. Thirty normal subjects divided into three age
      groups (18-44, 45-59, 60-80) underwent examination by means of the described
      system. During the test a random sequence of two words was presented to the
      subjects; the protocol consisted of an immediate reading task and two delayed
      reading tasks with variable foreperiods of 0.1 and 1.5 s for one task and 0.5 and
      4 s for the other. The analysis of the resultant acoustic and electromyographic
      signals indicated that reaction times increased with age in both the immediate
      and delayed tasks. The analysis of variance showed that the difference between
      the young and elderly groups was statistically significant. The sample size of
      the groups, however, is too small to consider these results normative data.

PMID- 7649500
TI  - The D2 dopamine receptor gene as a predictor of compulsive disease: Bayes'
      theorem.
AB  - The dopaminergic system, and in particular the dopamine D2 receptor, has been
      profoundly implicated in reward mechanisms in the meso-limbic circuitry of the
      brain. Dysfunction of the D2 dopamine receptors leads to aberrant substance
      (alcohol, drug, tobacco and food) seeking behavior. Decades of research indicate
      that genetics play an important role in vulnerability to severe substance seeking
      behavior. We propose that variants of the D2 dopamine receptor gene are important
      common genetic determinants in predicting compulsive disease.

PMID- 7649501
TI  - Primate models of cholinergic dysfunction.
AB  - Neuropathological studies are currently providing extensive information upon
      which to base experimental models of neurodegenerative diseases. While it seems
      unlikely that a single model encompassing all aspects of degenerative dementia
      will be developed in the near future, models that are more restricted in their
      scope can provide useful data about processes which range from cellular to
      behavioral disturbances. In this article we present recent primate studies
      revealing that mature basal forebrain cholinergic neurons degenerate as a
      consequence of the removal of their target. Both fimbria fornix transection and
      cortical devascularization seem to be useful tools in the assessment of potential
      neurotrophic and neuroprotective properties of pharmacological agents.

PMID- 7649502
TI  - A model of preventive psychosocial care for people with HIV disease.
AB  - People suffering from human immunodeficiency virus (HIV) infection have vast
      psychosocial needs that begin with diagnosis and evolve over the course of the
      illness. The medical focus has changed from intervention primarily in acute
      medical crises to prevention and outpatient monitoring for people with HIV
      disease. This article describes a structure that allows hospital social workers
      to intervene early, to carry out comprehensive assessments, and to continually
      follow a person with HIV disease throughout the course of illness. The article
      provides a framework of preventive psychosocial care for people with HIV disease,
      with particular attention to the use of a specialized assessment.

PMID- 7649503
TI  - Attitudes toward and knowledge of AIDS among African American social work
      students.
AB  - Social work students can be trained to assume critical roles in response to the
      acquired immune deficiency syndrome (AIDS) epidemic in the African American
      community. To effectively prepare social work students for these roles, educators
      must ascertain the knowledge and attitudes of students toward the epidemic.
      Although several researchers have studied the AIDS knowledge and attitudes of
      social work students in general, none have reported on the knowledge and
      attitudes of African American social work students as a group. In the present
      study, 48 graduate-level African American social work students responded to a
      questionnaire to measure these characteristics. Many students had incomplete
      knowledge about AIDS, felt unprepared to handle AIDS practice situations, and
      felt apprehensive about contact with people with AIDS. Social work educators need
      to take steps to ensure that African American social work students are prepared
      to intervene effectively in the AIDS epidemic.

PMID- 7649504
TI  - Effects of a fast-track closing on a nursing facility population.
AB  - Sixty-nine patients in a nursing facility were subjected to sudden, forced
      relocation to other nursing facilities when the facility they were in failed to
      meet conditions for participation in the Medicaid program. A retrospective study
      was conducted to examine the effects one year after transfer. Comparisons between
      those returned following recertification of the facility and those not returned
      demonstrated dramatic differences; 65 percent of the first group suffered
      deterioration or death, compared with 19 percent of the second group. Other
      factors found to be associated with high death rates or worsening of condition
      one year later were being male, severe physical or mental impairment, and lack of
      social support. Findings verify that serious adverse effects occur when
      unprepared patients are suddenly relocated and suggest that return to the
      facility of origin can mitigate those effects. Implications for policy and
      practice are discussed.

PMID- 7649505
TI  - Clozapine and the treatment of schizophrenia.
AB  - Clozapine, an atypical antipsychotic medication, is the most significant
      pharmacological advancement in the treatment of chronic schizophrenia in years.
      Effective in treating the nearly 30 percent of people with schizophrenia who do
      not respond to conventional pharmacological and psychosocial therapies, clozapine
      offers new hope to many. However, high cost, a potentially lethal side effect,
      and a weekly mandatory monitoring system have hampered access to clozapine
      treatment. This article reviews a brief history of clozapine use in the United
      States and also the unique features of the medication. Economic, ethical, and
      personnel resource issues of clozapine use are summarized. The author describes
      her clinical experiences with the psychosocial issues faced by those who respond
      to clozapine treatment, case highlights, and social work interventions. Social
      work advocacy for increased access to clozapine, the potential contributions of
      social workers in the selection of patients for treatment, and the logistical
      management issues confronting social workers in inpatient and outpatient mental
      health settings are addressed.

PMID- 7649506
TI  - Management of alternate level of care patients using a computerized database.
AB  - The term "alternate level of care" (ALC) refers to the status of hospitalized
      patients who are no longer acutely ill but cannot be discharged because
      posthospital plans are not yet in place. ALC is a major problem for patients,
      families, and hospitals. This article describes the experiences of an urban
      teaching hospital with ALC and the development of a computerized database to
      better manage the ALC population. Among the findings were that age, waiting for a
      nursing home placement, family-related discharge problems, and pending Medicaid
      eligibility all significantly contributed to length of stay beyond the acute
      phase of the illness. Using these data, the hospital developed an innovative
      program in which the preparation of Medicaid applications was transferred from
      the Department of Finance to the Department of Social Work Services.

PMID- 7649507
TI  - The Persian Gulf conflict: the impact of stressors as perceived by Army
      reservists.
AB  - This study examines the extent to which certain stressors influenced U.S. Army
      Reserve soldiers and their families as a result of the Persian Gulf conflict.
      Family composition, location of the soldier, rank, and gender were variables used
      to make comparisons of how the stressors affected soldiers and their families.
      Results revealed that married soldiers suffered from greater stress overall than
      single soldiers. Lower ranking soldiers and their families were affected less by
      the stressors outlined in this study than higher ranking soldiers and their
      families. Female soldiers were influenced less by the stressors than their male
      counterparts. Single-parent families handled the stressors better than two-parent
      families, and families with three or more school-age children responded better to
      the stress indicators than families with no children in school. On the basis of
      these results, clinical implications are discussed.

PMID- 7649508
TI  - Managed care's silent seduction of America and the new politics of choice.

PMID- 7649509
TI  - Integrating geriatric case management into primary care physician practices.

PMID- 7649510
TI  - Beyond the rhetoric: shared responsibility versus the Contract with America.

PMID- 7649511
TI  - A strengths perspective: an ethnographic study of homeless women with children.
AB  - Homeless women with children have been one of the fastest growing homeless
      subpopulations during the past decade. However, research in this area has paid
      scant attention to the needs of these homeless families. The ethnographic study
      of homeless women with children described in this article captures the prevailing
      strengths of this population. The women's strengths were identified in seeking
      housing, caring for children, and remaining connected to social contacts to keep
      their families together. The authors suggest that ethnography provides guideposts
      for social workers as they search for practice models.

PMID- 7649512
TI  - [Maximal force measurements of lip and tongue pressures and their significance
      for the diagnosis of orofacial dyskinesias].
AB  - The functioning of the orofacial muscular system essentially determines the shape
      of the jaw and of the dental arch as well as the position of the axis of the
      anterior teeth. Disturbances of the normal functioning can cause anomalies of the
      position of teeth or malformations of the bone structure. With the help of the
      newly developed device "Myometer 160" we now have the possibility to measure the
      intra- and extraoral forces. We examined 107 persons aged 8 to 37 years. The
      maximal force was measured by ventral tongue pressure, when the lips were pressed
      against each other and when a brass button was pulled. In addition clinical
      results as well as a functional status were ascertained in order to record
      orofacial dyskinesias. A significant connection between the age respectively the
      sex of the persons and the determined force was found. However, no clear
      relationship between the occlusal position respectively the functional anomaly
      and the results of maximal force was determined. Thus it does not seem sensible
      to use maximal force measurement within the framework of the determined. Thus it
      does not seem sensible to use maximal force measurement within the framework of
      the diagnosis of orofacial dyskinesias.

PMID- 7649513
TI  - [Clinical experiences with the torque-segmented arch (TSA)].
AB  - The torque segmented archwire presented here led to a good torque transfer in all
      patients, however this transfer differed on a case by case basis. With regard to
      the angle 1-NA, the average monthly torque change was 2.34 degrees. The smallest
      torque transfer was 1 degree; the biggest 5.5 degrees per month. Because the
      torque segmented arch wires consist of a pseudoelastic material for the anterior
      teeth and a steel portion for the lateral teeth, the anterior component can be
      adapted to the patient's individual situation and in addition the lateral
      components make possible the bending of first, second and third order bends. The
      dimensions of the superelastic materials are 0.016 x 0.022, 0.017 x 0.025, and
      0.018 x 0.025. In all 3 dimensions it is possible to select a torque of 30
      degrees or 45 degrees. The use of such arch wires yields the following
      advantages: 1. Problem-free adaptation to the patient's individual situation. 2.
      Torque segmented arch wires can be applied in the case of the standard edgewise
      technique as well as in each case of the straight wire technique. 3. The
      practitioner is no longer dependent on the torque loss of the archwire and the
      individual axial position of the incisors. 4. With the help of the torque key it
      is possible at any time to control the already transferred torque with regard to
      the occlusal plane. 5. The torque segmented archwire can also be applied in the
      segmented archwire technique. 6. The torque segmented archwire with right angular
      or round lateral components is well suited for the retraction of the anterior
      area.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7649515
TI  - [The effect of molar position on the distalization behavior of indirect
      headgear].
AB  - The asymmetric indirect headgear is a frequently used method to achieve an
      unilateral distalization of a molar. Cases have been observed, however, in which
      the distalization does not proceed in the way or to the degree predicated by the
      geometry of the outer bow. Among other factors, this discrepancy can be
      attributed to the geometry of the inner bow. This study demonstrates
      quantitatively and qualitatively the influence unilateral mesial movement and/or
      molar rotation exerts on the force system of the indirect headgear. The study
      makes evident that a neutralization of the molar's sagittal asymmetrical position
      by means of adjusting the length of the inner bow cannot be omitted. The study
      recommends the use of special headgear tubes extended in an oro-vestibular
      direction to eliminate the asymmetrical dynamics which arise in cause of the
      mesial rotation of a molar.

PMID- 7649514
TI  - [The dental and skeletal effects of the jumping-the-bite plate and high-pull
      headgear combination. A clinical study of treated patients].
AB  - While planning treatment of the 30 patients with a dental and skeletal class II
      anomaly on which this study is based, the primary treatment goals were correction
      of the dental and skeletal structures and attenuation of vertical growth by means
      of influencing the maxillary skeletal structures and the resultant mandibular
      reaction. The desired treatment results were achieved in all patients. Even so,
      however, the effects on individual patients in respect to skeletal influences
      were markedly different. It was especially helpful that during therapy
      simultaneously with exerting influence on the maxillary base plane, the
      influencing of the occlusal plane occurred in the same direction. Through the
      additional application of high-pull headgear, maxillary growth was clearly
      restrained and the inclination of the maxillary base plane inhibited. Even
      difficult skeletal discrepancies, sagittal as well as vertical, can be treated
      with the bite-jump appliance in combination with a high-pull headgear. This also
      makes it possible to achieve protrusive repositioning of the mandible in patients
      with a pronounced vertical growth pattern without causing on open bite. In
      retrospective the patients' treatment plans proved to be completely appropriate,
      however, the fact should not be overlooked that changing the occlusal plane is
      essential for the realization of a positive therapeutic result.

PMID- 7649516
TI  - [Biomechanical testing of the new torque-segmented arch (TSA)].
AB  - New torque-segmented arch wires are presented which consist of a superelastic
      anterior component with 30 degrees or 45 degrees torque and which are connected
      to 2 steel lateral components by means of a crimped connector. When using such
      torque-segmented arch wires, the crimped connector rests mesially to the canine
      bracket and the lateral components exhibit a torque of 0 degree. The use of the
      torque-segmented arch wires requires the practitioner to adjust the anterior
      tooth segment, to bend in first order bends in the steel lateral portion as well
      as to bend in a sweep to avoid an anterior tooth extrusion, and, if desired, to
      bend in third order bends to influence premolars and molars. In some cases the
      simultaneous application of palatal arches can become necessary, because each
      torque transfer results in a transversal enlargement in the molar area. Compared
      to conventional steel wires with dimensions of 0.016 x 0.022 in which an anterior
      tooth torque is bent, the torque segmented arch wires exhibit considerably fewer
      side effects, but there is a larger distally rotating moment for the molars. 1.
      When applying torque-segmented arch wires, the extrusive force transferred to the
      anterior teeth is considerably smaller. 2. The protrusive force acting on the
      anterior teeth is also considerably smaller, which results in a reduced demand
      being placed on the anchorage of the molars. 3. The torque transfer to the
      incisors rests in a quite moderate range, even in the case of a 50 degrees
      torque. For this reason, the practitioner can expect diminished or no resorptions
      at all compared to the aforementioned steel wires. 4. The Martensite plateau of
      the torque-segmented arch wires exhibit constant moments in large areas so that
      such arch wires can be used in almost every anterior tooth position. 5. The
      segmented wires presented here can be applied not only in the case of the
      standard edgewise technique but also in each case of the straight-wire technique.
      6. These new arch wires require no readjustment of torque values. 7. To control
      the transferred torque values it is recommended that the already transferred
      torque values be monitored during each check-up with the help of the described
      torque key. 8. When the torque values of the brackets are known, the torque key
      renders frequent patient X-rays superfluous. 9. When the desired torque values
      are attained, treatment can proceed using conventional arch wires.

PMID- 7649517
TI  - [Allergy induced by latex rubber containing products].

PMID- 7649518
TI  - Male breast cancer--a report of 4 cases and a review of the literature.
AB  - Male breast cancer represents only about 1% of all breast cancers. Of 451
      patients with breast cancer, we have experienced four cases of male breast
      cancer. Characteristics of these male patients with breast cancer were an older
      age at diagnosis (mean: 68.5 years old), prolonged duration of symptom (ranged
      from 1 month to 6 years with a mean of 25.5 months), centrally located tumor,
      advanced staging and infiltrating ductal carcinoma in histologic type. Some
      reported risk factors for the development of male breast cancer, such as
      radiation exposure, hormonal factors and gallstone disease were present.

PMID- 7649519
TI  - An autopsy case of B-cell lymphoma associated with macroglobulinemia (IgM-k).
AB  - While he was treated for macroglobulinemia showing symptoms, a 65-year-old man
      developed an enlargement of the left lateral cervical lymph node. Biopsy
      specimens of the cervical lymph node revealed large-cell non-Hodgkin's lymphoma.
      The lymphoma cells had rearrangement in the immunoglobulin heavy chain and kappa
      light chain genes. There was osteolysis involving right metatarsal bones. And, a
      tumor appeared on the upper hard palate in the terminal stage. Autopsy specimens
      showed infiltration of lymphoma cells into multiple organs. Production of
      monoclonal immunoglobulin M was detected only slightly and focally in the tumors.
      Plasmacytic differentiation as in Waldenstrom's macroglobulinemia was not seen in
      any organs except the tumor on the upper hard palate. From these findings, it is
      speculated that B-cell lymphoma might have developed in the course of
      macroglobulinemia.

PMID- 7649520
TI  - Effect of growth hormone treatment on quality of life of short-stature children.
AB  - While enhanced growth velocity is a well-established benefit following the
      initiation of growth hormone treatment (GHT), the potential benefit of GHT on
      quality of life (QOL) of short-stature children has not yet been documented. We
      compare QOL of two groups of short-stature children who attended the Endocrine
      Unit (EU) and were 2 SD or more below the average for age and gender. The first
      group included 96 patients of whom 65 were without any underlying disease, 15 had
      classical GH deficiency and 16 had Turner syndrome or renal disease. These
      patients were on GHT for at least 2 years. The other group included 33 patients.
      Owing to lack of resources to include these 33 patients in a clinical trial, they
      did not get GHT. They were normal variant of short stature, and their height was
      similar to the height of the 65 children included in the first group. QOL was
      assessed using self-administered questionnaires, which were filled out by the
      patients on their regular visit to the EU. QOL was defined in terms of school
      achievements, leisure activities, emotional and physical self-esteem,
      relationships with peers and family members. No significant differences were
      found between the two groups. The mean scores for the different domains of QOL
      ranged between 2.6 and 3.8 on a scale ranging from 1 (very pessimistic view) to 4
      (very optimistic view).

PMID- 7649521
TI  - Bone age at discontinuation of medroxyprogesterone acetate therapy in girls with
      precocious puberty: effect on final height.
AB  - To determine the final height of patients with precocious puberty treated with
      medroxyprogesterone acetate (MPA; 150 mg every week) for a period > 1 year (mean
      +/- SD = 3.24 +/- 1.85 years), data from a group of 26 girls were analyzed. The
      attained final height was 155.6 +/- 8.06 cm (-1.1 SD of the normal population).
      In a group of 8 untreated girls with precocious puberty, adult height was 149.2
      +/- 5.07 (-2.16 SD, p < 0.02). In 9 patients in whom treatment was stopped at a
      bone age < or = 12 years, final height was 159.2 +/- 10.05 cm, while in 16 girls
      who had a bone age > 12 years at the end of treatment, the final height was
      153.03 +/- 6.28 cm. Our data demonstrate the effectiveness of MPA treatment on
      ultimate height. The better height observed in those patients who stopped
      treatment with a bone age < 12 years suggests the advantage of discontinuing
      therapy before reaching a more advanced degree of skeletal maturation.

PMID- 7649522
TI  - Altered insulin resistance is associated with increased dietary weight loss in
      obese children.
AB  - To determine the relationship between insulin resistance and weight loss in early
      obesity, we used the euglycemic, hyperinsulinemic clamp to study the effect of a
      14-day weight reduction diet in 10 prepubertal and early pubertal obese children
      (age, 10.1 +/- 1.6 years) on insulin sensitivity. Body weight decreased from 73.7
      +/- 6.0 kg to 69.1 +/- 5.8 kg (p < 0.01). Insulin sensitivity before weight
      reduction negatively correlated with the amount of weight loss during diet (r = 
      0.8, p < 0.005). Weight loss also positively correlated with height standard
      deviation score (r = 0.9, p < 0.005). Mean insulin sensitivity increased from
      0.068 +/- 0.01 (nmol kg-1 min-1)/(pmol l-1) to 0.096 +/- 0.030 (nmol kg-1 min
      1)/(pmol l-1) (p < 0.05, one-tailed test). These results indicate that weight
      reduction decreases insulin resistance in childhood obesity. The inverse
      relationship between insulin sensitivity and weight loss during calorie,
      restriction in these subjects suggests that insulin resistance may enhance weight
      loss during calorie restriction.

PMID- 7649523
TI  - The importance of thyroglobulin levels in monitoring the treatment of congenital
      hypothyroidism.
AB  - We have previously reported on high thyroid-stimulating hormone (TSH)
      concentrations in clinically euthyroid children with congenital hypothyroidism
      (CH) undergoing appropriate treatment. Whether this TSH is biologically active or
      not is still unclear. It has been shown that ectopic thyroid tissue does not
      involute during thyroxine (T4) therapy and thus can continue to secrete
      thyroglobulin (Tg). This study was undertaken to determine whether the Tg levels
      in ectopic CH infants represent residual thyroid tissue stimulated by
      biologically active TSH and whether this Tg can be used to help monitor CH
      treatment. Among the 51 primary CH children (age 2-14 years) diagnosed and
      followed up by us, 28 had measurable Tg values (> 2 pmol/l) several years after
      the T4 treatment had been started. In 8 of the children, Tg was measured as early
      as the time of diagnosis and followed up for at least 3 years. The Tg levels
      decreased much more slowly than the TSH levels did, and secondary Tg rises were
      observed. By 5 months of age, all children had Tg levels less than 25 pmol/l.
      Although in some infants the Tg levels paralleled TSH behavior, in others the TSH
      Tg correlation was not so obvious. In another group of 8 children who had high
      TSH values despite normal T4, the LT4 replacement dosage was increased by 60% for
      1 week (from 3.5 +/- 0.2 to 5.5 +/- 0.5 micrograms/kg/day) in order to examine
      the TSH-Tg dependence.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7649524
TI  - Effects of thyroid status on thyroid autoimmunity expression in surgically
      induced hypothyroid patients with Graves' disease.
AB  - We investigated, in 20 patients with Graves' disease and presenting with both a
      surgically induced hypothyroid state and increased serum antibodies (Ab) to the
      TSH receptor (R) levels, the relationships between thyroid status and the serum
      TSH-R or peroxidase (TPO) Ab levels under L-T4 treatment and after L-T4
      cessation. The prevalence of positive TSH-R Ab (100%) and the log mean TSH-R Ab
      level (1.41 +/- 0.04%) observed during the surgically induced hypothyroid state
      decreased (p < 0.001, p < 0.01, respectively) under L-T4 therapy (prevalence of
      positive TSH-R Ab = 50%, log mean TSH-R Ab level 1.21 +/- 0.05%) and increased
      again (p < 0.001) after L-T4 cessation (prevalence of positive TSH-R Ab = 85%,
      log mean TSH-R Ab level = 1.45 +/- 0.06%) to reach levels lower (< 0.01) than
      that observed during the hypothyroid state for prevalence of positive TSH-R Ab
      but similar to that obtained during such a state for log mean TSH-R Ab value. The
      log mean TPO Ab level obtained during the surgically induced hypothyroid state
      (3.2 +/- 0.5 titer) decreased (p < 0.02) under L-T4 therapy (1.8 +/- 0.2 titer)
      and increased again (p < 0.02) after L-T4 cessation (3.0 +/- 0.5 titer) to reach
      a similar level to that obtained during the surgically induced hypothyroid state.
      There were positive correlations between log TSH levels and log TSH-R Ab values
      (r = 0.40, p < 0.001) or log TPO Ab levels (r = 0.33, p < 0.01).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7649525
TI  - Low adrenal androgens in men with HIV infection and the acquired immunodeficiency
      syndrome.
AB  - Using gas chromatography and mass spectrometry we have studied the ratios of
      steroid metabolites and 24-hour urinary steroid excretion rates in 37 men of whom
      14 where positive for the human immunodeficiency virus (HIV; group A), while 9
      had acquired immunodeficiency syndrome (AIDS; group B). Controls were sick non
      AIDS patients admitted to an intensive care unit (ICU) and healthy volunteers. In
      groups A and B and the ICU controls, there was a reduction in the excretion of
      adrenal androgen metabolites and a reduced ratio of 5 alpha to 5 beta androgen
      metabolites. These data suggest that adrenal androgens are removed in HIV and
      AIDS in a similar manner to other systemic illnesses. In group B patients and the
      sick controls, the ratios of cortisol to cortisone metabolites were raised
      compared with controls. Daily, total cortisol metabolite excretion rates in AIDS
      were similar to those in patients in the ICU. The selective loss of adrenal
      androgens may be mediated by cytokines and influence components of the immune
      system. The progression of HIV to AIDS may be due in part to an imbalance between
      androgens and glucocorticoids.

PMID- 7649526
TI  - Effect of growth hormone on IGF-I levels in a patient with growth hormone
      deficiency and Wilson disease.
AB  - This is a case report of a boy with a combination of two rare disorders:growth
      hormone deficiency (GHD) and Wilson disease. To our knowledge, no comparable case
      has yet been published in the literature. GHD was diagnosed at the age of 4.5
      years (height standard deviation score (SDS) -4.85). However, because of a
      difficult family background, growth hormone (GH) therapy could not be started.
      The boy was not seen again until the age of 7.7 years (height SDS -4.77), when
      GHD was reconfirmed and GH therapy could be initiated (dose 0.6 IU/kg/week). At
      that time, elevated liver enzymes (GPT 128 U/l, GOT 67 U/l, gamma-GT 28 U/l)
      confused diagnostic procedures. On GH, growth velocity SDS increased from -1.86
      to +4.50 in the first year and +3.87 in the second year, and height SDS increased
      to -4.26 and -3.59. However, serum IGF-I levels did not normalize (max. 67
      ng/ml), and liver enzymes were still elevated. At the age of 10 years, Wilson
      disease was diagnosed in view of low concentration of serum ceruloplasmin,
      elevated urinary copper excretion and high copper content in a liver biopsy
      sample. Under a combined therapy with D-penicillamine and GH, serum liver enzymes
      decreased, and IGF-I levels increased to normal. Height SDS for chronological age
      has improved constantly.

PMID- 7649528
TI  - 34th Annual meeting of the European Society for Paediatric Endocrinology (ESPE).
      Edinburgh, June 25-28, 1995. Abstracts.

PMID- 7649527
TI  - Growth hormone treatment in adults with childhood onset growth hormone
      deficiency: effects on psychological capabilities.
AB  - The psychological aspects (personal traits, way of relating to the surrounding
      environment, perception of body image, degree of self-esteem) of eight adults
      with childhood onset growth hormone (GH) deficiency (GHD) were studied before and
      after 6 months of recombinant GH therapy. Each subject was evaluated using the
      following tests: the Bem Sex Role test, the non-verbal scales of the WAIS test
      for adults, the State-Trait Anxiety Inventory, the Experiential-World Inventory,
      the Image-Marking Method and the Draw-a-Person test; a psychoneurophysiological
      profile was also evaluated in order to monitor, by means of four
      neurophysiological variables (muscular tension, galvanic resistance, skin
      temperature and heart rate), the reactions to specific and aspecific stress.
      Before treatment, adults with GHD tended to underestimate their body size by an
      average of 30%, with peaks of 47% for the head area; furthermore, they showed a
      low level of self-esteem, a closed attitude towards social relationships, a
      pessimistic attitude with a tendency towards depression and a strong sense of
      detachment from the outside world. After 6 months of GH treatment, patients
      presented an overall improvement in relation to intellectual tasks, accompanied
      by a lower level of stress during their performance. A clear improvement was also
      observed in terms of emotional control during specific and aspecific stress,
      which might contribute a positive effect on their interrelationships. As
      expected, the treatment was not able to reduce the subjects' highly distorted
      perception of body image, due to the fact that GH treatment, despite a clear
      amelioration of lean/fat body mass ratio, did not change their body
      proportions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7649529
TI  - Alpha-globin gene haplotypes in South American Indians.
AB  - The haplotypes of the alpha-globin gene cluster were determined for 99 Indians
      from the Brazilian Amazon region who belong to 5 tribes: Wayampi, Wayana-Apalai,
      Kayapo, Arara, and Yanomami. Three predominant haplotypes were identified: Ia
      (present in 38.9% of chromosomes), IIIa (25.8%), and IIe (22.1%). The only alpha
      globin gene rearrangement detected was alpha alpha alpha 3.7 I gene triplication
      associated with haplotype IIIa, found in high frequencies (5.6% and 10.6%) in two
      tribes and absent in the others. alpha-Globin gene deletions that cause alpha
      thalassemia were not seen, supporting the argument that malaria was absent in
      these populations until recently. The heterogeneous distribution of alpha-globin
      gene haplotypes and rearrangements among the different tribes differs markedly
      from the homogeneous distribution of beta-globin gene cluster haplotypes and
      reflects the action of various genetic mechanisms (genetic drift, founder effect,
      consanguinity) on small isolated population groups with a complicated history of
      divergence-fusion events. The alpha-globin gene haplotype distribution has some
      similarities to distributions observed in Southeast Asian and Pacific Island
      populations, indicating that these populations have considerable genetic
      affinities. However, the absence of several features of the alpha-globin gene
      cluster that are consistently present among the Pacific Islanders suggests that
      the similarity of haplotypes between Brazilian Indians and people from Polynesia,
      Micronesia, and Melanesia is more likely to result of ancient common ancestry
      rather than the consequence of recent direct genetic contribution through
      immigration.

PMID- 7649530
TI  - Evolutionary relationships between black South American and African populations.
AB  - Data related to ten protein genetic loci expressed in blood obtained from four
      South American black populations were compared with data from seven African
      countries. Estimates of admixture among South American blacks were revised, and
      several indexes of gene diversity and genetic distances between the 11
      populations were calculated. The admixture values and genetic relationships
      observed among the South American black communities conform well with those
      expected on historical grounds, and they show only moderate reductions in genetic
      diversity.

PMID- 7649531
TI  - Geographic and ethnic distributions of the more frequent cystic fibrosis
      mutations in Europe show that a founder effect is apparent for several mutant
      alleles.
AB  - Examination of the European geographic patterns of the 10 relatively most
      frequent cystic fibrosis mutations, other than the DF508 one, shows that a
      founder effect is apparent for a number of them. The most evident examples are
      for the W1282X mutation in Jews, with a probable Asian origin, and the G551D and
      R117H mutations in Celts. Geographic distributions indicate that the main focus
      of the 621 + 1 G-->T and DI507 mutations is probably located in Wales. Also, the
      R1162X mutation probably originates from a circumscribed north Italian region.
      The N1303K mutation has a wide range in Europe with a clear preponderance in
      southern countries. Even the relatively common G542X and 1717.1 G-->A mutations
      have a local preponderance in Spain and Sicily and in northern Italy,
      respectively. Likelihood estimates for recurrent mutation and identity by descent
      strongly support the hypothesis of recurrence for the (mainly German) mutation
      R553X.

PMID- 7649532
TI  - Origins of Indo-Europeans and the spread of agriculture in Europe: comparison of
      lexicostatistical and genetic evidence.
AB  - A series of tests was undertaken to relate lexicostatistical dissimilarities
      (LAN) among 48 Indo-European languages to distances representing various causal
      hypotheses. The comparison is limited to languages currently spoken in Europe.
      The putative causal distance matrices include (1) geographic (GEO) distances
      between the languages, (2) distances representing the origin of agriculture
      (OOA), (3) distances representing a model postulated by C. Renfrew (REN)
      concerning transformations that gave rise to the major Indo-European language
      families in Europe, and (4) distances representing a competing hypothesis by M.
      Gimbutas (GIM) concerning the origin and spread of Indo-European languages in
      Europe. Pairwise Mantel tests of the matrices show that OOA correlates better
      with LAN than does REN, supporting Renfrew's basic hypothesis of the dispersal of
      the Indo-European languages with the spread of agriculture but showing less
      effect for his postulated transformations. Partial correlation of LAN with OOA
      when GEO is held constant is significant at p = 0.004, whereas REN is no longer
      correlated with LAN when GEO is held constant. When repeated for only seven
      languages chosen to represent the seven major families of Indo-European languages
      currently spoken in Europe, the results differed appreciably, yielding a
      negative, albeit nonsignificant, partial correlation between OOA and LAN when GEO
      is held constant. This apparent contradiction led us to develop some new
      statistical approaches to examine, confirm, and explain the patterns. Decomposing
      the Mantel correlation coefficients for the 48 Indo-European languages into
      several additive correlation components showed that much of the positive
      component of the correlation coefficient was contributed by LAN, OOA correlation
      within language families, particularly within the Germanic family, covering up
      the negative contributions between language families. The differentiation of the
      seven major Indo-European language branches in Europe seems unrelated to the
      times of the origin of agriculture. This finding fails to support the fundamental
      assumption of Renfrew's hypothesis. There are also no significant correlations
      between LAN and REN or GIM. A series of Monte Carlo experiments confirmed these
      findings. Consideration of the accumulated evidence from genetics supports the
      model of demic diffusion during the origin of agriculture. However, published
      genetic studies and the present study lend no support to the notion that the
      early farmers were indeed the Indo-Europeans.

PMID- 7649533
TI  - Worldwide analysis of genetic and linguistic relationships of human populations.
AB  - In this study we relate language differences on a global scale with genetic
      distances for the same populations. The analysis is carried out on more
      populations (130) but fewer genetic systems (11) than earlier studies. We
      constructed an overall genetic distance matrix that allowed for missing values. A
      separate genetic distance matrix was also computed for each genetic system, and
      matching matrices of linguistic and geographic distances were associated with
      each genetic distance matrix, because the number of populations used differed
      among the genetic systems studied. Significant matrix correlations between
      language and genetics were found for both overall genetic distances and a
      substantial number of genetic systems, even when the effects of geographic
      distances were held constant. This demonstrates a significant correspondence
      between genetics and language on a global scale. Genetic matrices were correlated
      with two different linguistic distance matrices: one with higher (supraphyletic)
      taxonomic structure, in which among other features sub-Saharan Africans separate
      from non-Africans in the basal split and the Eurasiatic superphylum is
      postulated; and one without such structure. The correlations yield no genetic
      evidence to support the proposed higher linguistic structure. UPGMA and neighbor
      joining trees were constructed for linguistic and genetic data. The proposed
      African split pattern is not supported by these data. Both types of trees
      indicate a pattern of grouping of east Asians, Arctic populations, and Australian
      natives separating from Caucasoid and African populations.

PMID- 7649534
TI  - Surname sampling for the study of the genetic structure of an Italian province.
AB  - Italian provinces may constitute a basic geographic unit that is big enough to be
      genetically structured but small enough to be analyzed intensively. In the
      present study surnames starting with three different letters of the alphabet were
      sampled from the telephone directory and used as a relatively simple and
      efficient way to cast light on the genetic and demographic pattern of the
      province and to prove the sampling efficiency. The 189 communes of the province
      of Pavia were grouped into 13 subregions composed of geographically clustered
      communes, and the relationships among them were examined using principal
      components analysis (PCA) and cluster analysis. The three samples show a
      concordant pattern: The Po and Ticino rivers are geographic barriers and
      subdivide the province into three regions (Lomellina, Pavese, and Oltrepo), which
      therefore appear to be genetifally differentiated. Both PCA and cluster analysis
      indicate that the main division is between the Oltrepo and the Pavese-Lomellina
      clusters and that it corresponds to the separation created by the Po River. The
      second split separates Lomellina from Pavese and thus parallels the Ticino River.
      The Lomellina subregions are more clustered than those of Pavese or Oltrepo.
      Furthermore, Lomellina has the highest number of surnames that are found only in
      a single area. This finding is possible due to endogamy dating back to an ancient
      border (valid until 1860) that separated Lomellina from the rest of Lombardy.
      Furthermore, Lomellina shows the highest frequency of surnames present only in
      one of the 13 subregions and the lowest percentage of unique surnames; both facts
      may describe genetic isolation of the area. A correlation is also seen between
      the percentage of surnames present only once in each of the 13 subregions and the
      census immigration rate: Both indicate the tendency of reduced immigration into
      the bigger towns. Particular discordances between the two estimates may reflect
      local or tourism-related migration.

PMID- 7649535
TI  - Effect of interregional migration on geographic variability in biological and
      social traits in Great Britain.
AB  - Over 19% of individuals born in England, Scotland, and Wales during March 3-9,
      1958, resided in 1981 in a region different from the region of their birth. This
      internal migration among the 11 regions increased geographic homogeneity for one
      genetic variable (ABO blood group). Cramer's V for mother's A, O, and B or AB
      blood group decreased from 0.0504 to 0.0476. Mother's Rh+/- blood group was not
      significantly different among regions of place of birth or subsequent place of
      residence of the offspring. Variability among the regions increased by migration
      from region of birth to region of residence 23 years later for the social class
      of male head of household (Cramer's V increased from 0.0815 to 0.0877) and for
      years of schooling completed (V increased from 0.107 to 0.129). Stature behaved
      more like the social variables (mean square deviation among regions increased
      from 371 cm2 to 481 cm2 in females and from 426 cm2 to 471 cm2 in males), but
      body weight tended to become more uniform among regions (mean square deviation
      decreased from 220 kg2 to 178 kg2 in females and from 315 kg2 to 260 kg2 in
      males).

PMID- 7649536
TI  - Geographic differences in seasonal variation of mean birth weight in Japan.
AB  - Seasonal variation of mean birth weight (MBW), mean gestational period (MGP), and
      MBW at 40 weeks of gestation (MBW40) in the 15 different prefectures of Japan
      were analyzed using vital statistics from 1974 to 1983. MBW generally shows a
      bimodal pattern with two peaks in spring and autumn and two troughs in summer and
      winter. Seasonality exhibits a general geographic trend: The autumn peak loses
      its height and the spring peak increases its amplitude as one moves from north to
      south. This trend suggests that environmental factors are associated with the
      creation of seasonality in MBW. For MGP the pattern is relatively unimodal with a
      deep trough in winter; however, a late summer small dip is observed in most
      cases. According to an analysis of coincidence between the two time series (MBW
      and MGP) and correlation analysis, the seasonal variation in birth weight
      basically depends on the gestational period. For MBW40, which represents the
      fetal growth rate, the seasonality shows a pattern similar to that of MBW. A
      statistically significant coincidence and a correlation are observed between the
      time series of MBW and MBW40. These results suggest that the two processes of
      fetal growth (gestational period and fetal growth rate) are associated with the
      creation of seasonality in MBW.

PMID- 7649537
TI  - Selective monitoring for a Chernobyl effect on pregnancy outcome in Kiev, 1969
      1989.
AB  - The aim of this investigation was to determine the frequency of adverse pregnancy
      outcomes in Kiev during the period surrounding the Chernobyl accident on April
      26, 1986. Additional effective equivalent doses resulting from the catastrophic
      irradiation in 1986-1991 was 8.04 mSv for Kiev inhabitants. We retrospectively
      analyzed the archives of the two largest obstetric hospitals between 1969 and
      1990. Spontaneous miscarriages, congenital anomalies, and perinatal mortality
      varied during the two decades without any pronounced changes in any direction.
      Additional long-term follow-up is needed to determine mutagenic or carcinogenic
      effects.

PMID- 7649539
TI  - Intracellular heteroplasmy for disease-associated point mutations in mtDNA:
      implications for disease expression and evidence for mitotic segregation of
      heteroplasmic units of mtDNA.
AB  - Studies in vitro have shown that a respiratory-deficient phenotype is expressed
      by cells when the proportion of mtDNA with a disease-associated mutation exceeds
      a threshold level, but analysis of tissues from patients with mitochondrial
      encephalomyopathy, lactic acidosis, and strokelike episodes (MELAS) have failed
      to show a consistent relationship between the degree of heteroplasmy and
      biochemical expression of the defect. One possible explanation for this
      phenomenon is that there is variation of heteroplasmy between individual cells
      that is not adequately reflected by the mean heteroplasmy for a tissue. We have
      confirmed this by study of fibroblast clones from subjects heteroplasmic for the
      MELAS 3243 (A-->G) mtDNA mutation. Similar observations were made with fibroblast
      clones derived from two subjects heteroplasmic for the 11778 (G-->A) mtDNA
      mutation of Leber's hereditary optic neuropathy. For the MELAS 3243 mutation, the
      distribution of mutant mtDNA between different cells was not randomly distributed
      about the mean, suggesting that selection against cells with high proportions of
      mutant mtDNA had occurred. To explore the way in which heteroplasmic mtDNA
      segregates in mitosis we followed the distribution of heteroplasmy between clones
      over approximately 15 generations. There was either no change or a decrease in
      the variance of intercellular heteroplasmy for the MELAS 3243 mutation, which is
      most consistent with segregation of heteroplasmic units of multiple mtDNA
      molecules in mitosis. After mitochondria from one of the MELAS 3243 fibroblast
      cultures were transferred to a mitochondrial DNA-free (rho0) cell line derived
      from osteosarcoma cells by cytoplast fusion, the mean level and intercellular
      distribution of heteroplasmy was unchanged. We interpret this as evidence that
      somatic segregation (rather than nuclear background or cell differentiation
      state) is the primary determinant of the level of heteroplasmy.

PMID- 7649538
TI  - Molecular basis of phenotypic variation in patients with argininemia.
AB  - Argininemia is an autosomal recessive disorder caused by a deficiency in the
      liver-type arginase enzyme. Clinical manifestations include progressive spastic
      diplegia and mental retardation. While the quality of life can severely
      deteriorate in most such patients, some do show remarkable improvement in
      neurological symptoms while on controlled diets. We examined the thesis that
      differences in clinical responses to dietary treatment are based on molecular
      heterogeneity in mutant arginase alleles. Genomic DNAs from 11 patients with
      argininemia were examined using the polymerase chain reaction, cloning, and
      sequencing. Nine mutations representing 21/22 mutant alleles were identified in
      11 patients with argininemia, and four of these mutations were expressed in vitro
      to determine the severity of enzymatic defects. We found that these mutations
      accounted for 64% of the mutant alleles in our patients. Based on findings in
      vitro expression tests, the mutations can be considered either severe or
      moderate. Patients with at least one moderate mutant allele responded well to
      dietary treatment; concentrations of plasma arginine were controlled within 300
      microM. In contrast, patients with two severely mutated alleles did not respond
      to dietary treatment and plasma arginine was over 400 microM. Argininemia is
      heterogeneous at the molecular level. The degree of clinical improvement during
      dietary treatment is reflected in the concentration of arginine in plasma, as a
      measure of metabolic control. Plasma arginine levels during treatment is
      reflected in the concentration of arginine in plasma, as a measure of metabolic
      control. Plasma arginine levels during treatment correlated with types of
      molecular defects in the arginase genes.

PMID- 7649540
TI  - Characteristic chromosomal fragility of human embryonic cells exposed in vitro to
      aphidicolin.
AB  - The frequency and distribution of aphidicolin (APC)-induced common fragile sites
      (cfs) were analyzed in human embryonic cells of different origins. Embryonic lung
      fibroblasts (MRC-5), amniocytes (AMINO) and embryonic retina cells (HERO790) are
      as sensitive to the APC-induced clastogenic effect as peripheral lymphocytes,
      whereas embryonic kidney cells (HEK) seem more resistant to the induction of
      chromosomal gaps and breaks by the drug. Analysis of the distribution of fragile
      sites confirmed that the expression of specific APC-induced cfs varies in
      different cells and that the embryonic cell strains show a greater similarity
      among themselves than to lymphocytes. In addition, HEK, MRC-5, HERO790 and AMINO
      cells show specific APC induction of the cfs at the 1p31.2 chromosomal band,
      which seems to be a distinctive feature of the embryonic stage of cells.

PMID- 7649541
TI  - Solid-phase minisequencing confirmed by FISH analysis in determination of gene
      copy number.
AB  - The solid-phase minisequencing method (Syvnen et al. 1990) allows accurate
      quantative determination of the ratio between two DNA or RNA sequences that are
      present as a mixture in a sample and differ from each other only by a single
      nucleotide. Here, we present another application of the minisequencing method,
      the determination of the gene copy number in a genome. The copy number of a
      marker gene aspartyl glucosaminidase (AGA) located at 4qter, was determined in
      three patients with a chromosomal alteration involving the distal region of 4q.
      For the minisequencing assay an equal amount of DNA from a patient homozygous for
      a mutation in the AGA gene was added to the DNA samples concerned. The relative
      amount of the normal sequence determined in each combined sample gives the copy
      number of the AGA gene. Fluorescence in situ hybridization (FISH), applied in
      parallel as a control, produced concordant results with solid-phase
      minisequencing in each case. As the potential of the minisequencing lies in
      automation, it could be a useful tool in the screening of monosomies, trisomies
      or loss of heterozygosity in diagnostics.

PMID- 7649542
TI  - The eighth component of human complement: molecular basis of C8A (C81)
      polymorphism.
AB  - Using an exon-specific polymerase chain reaction (PCR) followed by direct DNA
      sequence analysis we have analyzed the polymorphism of the alpha-chain of the
      eighth component of human complement (C8) at the DNA level. We found that two
      common alleles, C8A*A and C8A*B, are characterized by the substitution of a
      single amino acid (Gln to Lys), which is caused by a point mutation of a single
      nucleotide (C to A) in exon 3 at position 187 of the mature C8 alpha cDNA
      sequence. Based on this mutation, an allele-specific PCR was designed detecting
      the two alleles of C8A. We applied this method to type the C8A polymorphism using
      DNA samples from a Chinese Han population. The comparison with the data of
      protein typing of the same samples proved that the described method is efficient
      and reliable for the identification of C8A genotypes and may be valuable for
      further application in population studies and forensic science.

PMID- 7649543
TI  - Confirmation of linkage to 1q21-31 in a Danish autosomal dominant juvenile-onset
      glaucoma family and evidence of genetic heterogeneity.
AB  - Autosomal dominant juvenile-onset open-angle glaucoma has been mapped to 1q21-31
      in a number of American families. Our study confirms linkage in a Danish five
      generation dominant juvenile-onset glaucoma family with a maximum two-point lod
      score of 6.67 at the D1S210 locus. Multipoint linkage analysis in a nine
      generation Swedish family with dominant juvenile-onset glaucoma and iris
      hypoplasia excludes linkage to the region of approximately 18 cM between loci
      D1S104 and D1S218, shown to contain the previously mapped glaucoma gene. This
      study thus provides support for genetic heterogeneity with respect to dominant
      juvenile-onset glaucoma.

PMID- 7649544
TI  - De novo mutation in the mitochondrial ATP synthase subunit 6 gene (T8993G) with
      rapid segregation resulting in Leigh syndrome in the offspring.
AB  - The mutation in the mitochondrial ATP synthase subunit 6 gene (ATP6 T8993G) was
      identified in a male infant who died at age 15 months of Leigh syndrome. He had
      94% mutated mitochondrial DNA (mtDNA) in muscle and 92% in lymphocytes. His
      mother was healthy but had 37% mutated mtDNA in muscle and 38% in lymphocytes.
      The proband's brother, who was also healthy, had 44% mutated mtDNA in
      lymphocytes. No mutated mtDNA was detected in muscle and lymphocytes from the
      maternal grandmother of the proband or in lymphocytes from 15 other maternal
      relatives, showing that the first carrier of the ATP6 T8993G mutation in this
      family was the mother of the proband. This study shows that this point mutation
      may occur at substantial levels in a carrier of a de novo mutation and rapid
      segregation with high levels of mutated mtDNA causing neurodegenerative disease
      may occur in the second generation.

PMID- 7649545
TI  - Variation at the M235T locus of the angiotensinogen gene and essential
      hypertension: a population-based case-control study from Rochester, Minnesota.
AB  - A variant of the angiotensinogen gene, M235T, has been associated with essential
      hypertension in selected subjects from Paris, France and Salt Lake City, Utah. In
      the present report, we studied a population-based sample consisting of 104
      subjects diagnosed with hypertension before age 60 and 195 matched normotensive
      individuals from Rochester, Minnesota. We determined whether there was a
      relationship between the M235T polymorphism of the angiotensinogen gene and the
      occurrence of essential hypertension using two methods. First, a contingency chi
      square analysis was carried out to test for an association between the M235T
      polymorphism and hypertension status. Second, multivariable conditional logistic
      regression was used to determine whether variation at the M235T polymorphism was
      a significant predictor of the probability of having essential hypertension. We
      detected no statistically significant association between the M235T polymorphism
      and the occurrence of essential hypertension. In particular, the association was
      not significant in either gender or in a subset of severely hypertensive subjects
      requiring two or more anti-hypertensive medications. Furthermore, variation in
      the number of M235T alleles did not make a significant contribution to predicting
      the probability of having essential hypertension, either alone or in conjunction
      with other predictor variables. These results suggest that the contribution of
      variation in the angiotensinogen gene to the occurrence of essential hypertension
      is less than initially suspected, or may not be constant across populations.

PMID- 7649546
TI  - Screening for mutations in exon 4 of the LDL receptor gene in a German population
      with severe hypercholesterolemia.
AB  - A group of 218 patients with severe hypercholesterolemia (LDL cholesterol > 260
      mg/dl) living in the Cologne area were screened for mutations in the 3 half of
      exon 4 of the low density lipoprotein (LDL) receptor gene by the single-strand
      conformation polymorphism (SSCP) method. The analysed fragment was 242 bp in
      length and comprised approximately 6% of the coding region. In 11 patients an
      abnormal SSCP pattern was observed. Two of the abnormal fragment patterns were
      identical. The results of the SSCP screening could be confirmed by direct DNA
      sequencing. Three of the ten different mutations were previously described (3 bp
      deletion: codon 197; Asp200-->Gly; Glu207-->stop). Of the newly identified
      mutations there were two deletions, two insertions, one combined insertion and
      deletion mutation and two single base pair substitutions [1 bp deletion: G in
      codon 197; 37 bp deletion: T in codon 196-208 or AT in 196-207 and GA in codon
      208; 18 bp insertion: codon 201-206; 8 bp insertion: codon 155-156 and GA in
      codon 157; 6 bp insertion (codon 196-197) and 5 bp deletion (codon 199, C in
      codon 198 and G in codon 198 or 200); Asp200-->Tyr; Asp203-->Val]. The 8-bp
      insertion was detected in a second unrelated individual. The analysis of the
      functional consequences of the mutations indicates that all mutations were
      causative of the LDL cholesterol elevation.

PMID- 7649547
TI  - Gene defect in hypodontia: exclusion of MSX1 and MSX2 as candidate genes.
AB  - Hypodontia, congenital lack of one or a few teeth, is an autosomally inherited
      dominant trait. Homeobox genes MSX1 and MSX2 are expressed in presumptive dental
      tissues at the stage of initiation of tooth development. Recently, tooth
      development was shown to be inhibited in transgenic mice lacking a functional
      Msx1 gene. Here, we studied the relationship of the MSX1 and MSX2 genes to
      familial hypodontia in five Finnish families with a total of 20 affected
      individuals, by linkage analysis. The pairwise lod-scores regarding the
      intragenic microsatellites in the MSX1 and MSX2 genes at a recombination fraction
      of 0.0 were -3.1 and -3.0, respectively, thus excluding these genes as causative
      loci for hypodontia in these families.

PMID- 7649548
TI  - Mutations of the fibroblast growth factor receptor-3 gene in one familial and six
      sporadic cases of achondroplasia in Japanese patients.
AB  - Achondroplasia, the most common cause of chondrodysplasia in man, is
      characterized by short-limbed dwarfism, macrocephaly, and dysplasia of metaphyses
      of the tubular bones. Recently, mutations in the gene encoding fibroblast growth
      factor receptor-3 (FGFR-3) have been found in patients with achondroplasia. All
      mutations so far reported had occurred at codon 380, resulting in the
      substitution of an arginine for a glycine in the transmembrane domain of the
      predicted protein. We have examined the transmembrane domain of the FGFR-3 gene
      in seven Japanese patients with achondroplasia. Of the six cases that were
      sporadic, all carried a mutation in codon 380; the single familial case bore a
      novel mutation of a G-to-T transition at codon 375, which resulted in
      substitution of a cysteine for a glycine.

PMID- 7649549
TI  - Recurrent and novel LDL receptor gene mutations causing heterozygous familial
      hypercholesterolemia in La Habana.
AB  - The molecular basis of familial hypercholesterolemia (FH) in three families of
      Spanish descent from La Habana was investigated by the candidate gene approach.
      The Arg3500Gln mutation of apolipoprotein B-100 was not found. Identification of
      low density lipoprotein receptor (LDLR) gene haplotypes segregating with FH
      guided the characterisation of three point mutations by automated sequencing.
      One, a Val408-->Met missense mutation, a founder mutation in Afrikaner FH
      patients, was recurrent, being associated with a distinct DNA haplotype. The
      other two, Glu256-->Lys and Val776-->Met missense mutations, were novel and
      modified highly conserved residues. These mutations were absent in normolipidemic
      subjects and were associated in heterozygous carriers with twice the cholesterol
      levels observed in non-carriers. Noticeably, cardiovascular complications were
      rarely observed in older heterozygotes, even in those with the Afrikaner FH-2
      mutation. These findings confirm the molecular heterogeneity of LDLR gene
      mutations causing FH and the variability of their expression across different
      populations.

PMID- 7649550
TI  - RS46(DXS548) genotyping of reproductive cells: approaching preimplantation
      testing of the fragile-X syndrome.
AB  - In order to approach preimplantation testing for the fragile-X syndrome, we used
      genotyping of the polymorphic RS46(DXS548) locus closely linked to the FMR-1
      gene, in single reproductive cells of females. The RS46(DXS548) amplification was
      adjusted to the single cell level by a two-round polymerase chain reaction (PCR)
      procedure. Unfertilized oocytes and extruded polar bodies were subjected to PCR.
      RS46(DXS548) genotyping at the single cell level was successful in 95% of the
      samples. In two-third of the metaphase II oocytes and first polar bodies obtained
      from women who were heterozygous at the RS46(DXS548) locus, both maternal
      RS46(DXS548) alleles were observed because of crossing over during the first
      meiotic division. This makes gamete selection by first polar body analysis
      inefficient. From the allele frequencies found in 56 unrelated individuals, a
      heterozygote frequency of 51% was estimated, whereas the observed heterozygote
      frequency was 56%. The whole PCR procedure can be performed within 16 h after
      blastomere biopsy. Consequently, the selection and transfer of the diagnosed
      embryos can be carried out within an acceptable time. Therefore, preimplantation
      testing for the fragile-X syndrome with the RS46(DXS548) AC-repeat may be an
      alternative choice for prenatal testing for those carrier females who are
      heterozygous (informative) at the RS46(DXS548) locus.

PMID- 7649551
TI  - A recombination event occurring within two complex 5q13.1 microsatellite repeat
      polymorphisms suggests a telomeric mapping of spinal muscular atrophy.
AB  - The gene for the childhood spinal muscular atrophies (SMAs) has been mapped to
      5q13.1. The interval containing the SMA gene has been defined by linkage analysis
      as 5qcen-D5S629-SMA-D5S557-5qter. We have identified a recombination event within
      this interval on a type-I SMA chromosome. The recombination maps to a region of
      multilocus microsatellite repeat (MSR) markers, and occurs between different
      subloci of two such markers, CMS-1 and 7613. While the possibility of a novel
      mutation caused by the recombination cannot be discounted, we believe when viewed
      in the context of a similar recombination in a Dutch SMA family, a centromeric
      boundary at the recombination site for the critical SMA interval is likely. This
      new proximal boundary would reduce the minimal region harboring the SMA locus
      from approximately 1.1 Mb to approximately 600 kb.

PMID- 7649552
TI  - Mapping of a human rRNA gene in the YAC contig surrounding the SMA candidate
      gene.
AB  - Using the yeast artificial chromosome (YAC) 116 flanking the autosomal recessive
      spinal muscular atrophy (SMA) gene region, we have screened a human fetal brain
      cDNA library and isolated the cDNA clone 14-3/9 with an insert size of 2.5 kb.
      The cDNA clone could be identified as part of the human rRNA gene coding for 28S
      rRNA with a total size of 5025 bp. The human 28S rRNA is involved in the
      organization of the 60S ribosomal subparticle and is arranged in a 13-kb pre-rRNA
      transcription unit that occurs in tandem repeat clusters. Multiple copies of the
      rRNA gene have been mapped by pulsed field blot hybridization in the YAC contig
      between YAC 66 and YAC 116, which encompasses the SMA candidate gene, and
      additionally in the distally localized YAC 153.

PMID- 7649553
TI  - Characterization of a recombinant that locates the hereditary hemochromatosis
      gene telomeric to HLA-F.
AB  - The gene responsible for hereditary hemochromatosis has been shown to be closely
      linked to the HLA-A and D6S105 loci on the short arm of chromosome 6. Efforts at
      mapping the disease gene have been hindered, however, by a lack of informative
      recombinant in this region. We have identified two recombinant individuals in a
      single affected family and have confirmed recombination by analysis of 16
      polymorphic markers located near HLA-A and D6S105. One of the recombinants
      provides evidence for the location of the hemochromatosis gene telomeric to HLA
      F.

PMID- 7649554
TI  - A nonsense mutation (Gln-673-Term) in exon 17 of the human dystrophin gene
      detected by heteroduplex analysis.
AB  - Heteroduplex analysis was used to search for small mutations in a sample of 40
      Italian DMD/BMB patients in whom large rearrangements were not found. A novel
      nonsense mutation in exon 17 of the dystrophin gene, consisting of a C to T
      transition, is described.

PMID- 7649555
TI  - Investigations with fluorescence in situ hybridization (FISH) demonstrate loss of
      the telomeres on the reciprocal chromosome in three unbalanced translocations
      involving chromosome 15 in the Prader-Willi and Angelman syndromes.
AB  - Two patients with classical features of Angel-man syndrome (AS) and one with
      Prader-Willi syndrome (PWS) had unbalanced reciprocal translocations involving
      the chromosome 15 proximal long arm and the telomeric region of chromosomes 7, 8
      and 10. Fluorescence in situ hybridization (FISH) was used for the detection of
      chromosome 15(q11-13) deletions (with probes from the PWS/AS region) and to
      define the involvement of the telomere in the derivative chromosomes (with
      library probes and telomere-specific probes). The 15(q11-13) region was not
      deleted in one patient but was deleted in the other two. The telomere on the
      derivative chromosomes 7, 8 and 10 was deleted in all three cases. Thus, these
      are true reciprocal translocations in which there has been loss of the small
      satellited reciprocal chromosome (15) fragment.

PMID- 7649556
TI  - Haplotype analysis of common transthyretin mutations.
AB  - The most frequent transthyretin (TTR) variant associated with hereditary
      amyloidosis is TTR Met 30, which has its major focus in Portugal, although it
      also occurs in many other countries. The distribution of the mutation and its
      occurrence in a CpG dinucleotide lead us to question the origin of the mutation
      and the possibility of its having originated in Portugal. In order to investigate
      these questions, we studied the distribution of haplotypes associated with the
      Met 30 mutation in families from different European countries. All the analysed
      Portuguese families presented the same haplotype associated with the Met 30
      mutation (haplotype I). The same was found for the Swedish and Spanish families
      studied. However, a distinct haplotype (haplotype III) was found in three
      families, one Italian, one English and one Turkish. These results suggest that,
      although the Portuguese Met 30 carriers might have one founder, the mutation
      probably recurred in populations in Europe in a similar manner to that reported
      in Japan. In this study, we have also analysed the haplotypes associated with
      other TTR variants frequent in the Portuguese population.

PMID- 7649557
TI  - Two highly polymorphic CA repeats in the Menkes gene (ATP7A).
AB  - Two highly polymorphic CA repeats have been identified in the Menkes gene
      (ATP7A). These repeats should be useful for prenatal diagnosis and carrier
      detection in families with Menkes disease and X-linked cutis laxa. The observed
      heterozygosity for these two repeats was 0.778 and 0.60 in Centre d'Etude du
      Polymorphisme Humaine (CEPH) families.

PMID- 7649558
TI  - Metachromatic leukodystrophy: a 12-bp deletion in exon 2 of the arylsulfatase A
      gene in a late infantile variant.
AB  - Sequencing of the arylsulfatase A gene in a late infantile metachromatic
      leukodystrophy patient showed the presence of a 12-bp deletion in exon 2. This
      deletion was found in a compound heterozygous state with the previously described
      287 C-->T transition.

PMID- 7649559
TI  - Two further cases of mutation R1947X in the NF1 gene: screening for a relatively
      common recurrent mutation.
AB  - We present two further cases of mutation R1947X in the neurofibromatosis type 1
      gene. To date, a total of nine cases of mutation R1947X have been reported giving
      a frequency of about 2% and confirming the recurrence of this mutation. R1947X
      occurs within a CpG dinucleotide and supports the hypothesis that the mutation
      rate for this dinucleotide is higher than that of other dinucleotides. As routine
      analysis for R1947X is advisable, we have developed an allele-specific
      oligonucleotide hybridization assay for the efficient screening of a large number
      of samples.

PMID- 7649560
TI  - The MUC5AC gene: RFLP analysis with the Jer58 probe.
AB  - We have recently obtained evidence that the locus corresponding to three groups
      of partial tracheobronchial cDNAs (A = Jer47, B = Jer57, C = Jer58) which mapped
      to chromosome 11p15 and was given the symbol MUC5 corresponds to two distinct
      genes which we have provisionally called MUC5B and MUC5AC. Here we describe the
      detection, using the Jer58 probe, which contains a 24-bp tandem repeat, of
      polymorphism in the MUC5AC gene with seven different restriction enzymes.

PMID- 7649561
TI  - (CGG) trinucleotide repeat polymorphism in the 5' region of the HHR6B gene: the
      human homolog of the yeast DNA repair gene RAD6.

PMID- 7649562
TI  - Locus homogeneity for cartilage-hair hypoplasia proven?

PMID- 7649563
TI  - Specification of the phenotype required for men with monoamine oxidase type A
      deficiency.

PMID- 7649564
TI  - Repair mechanism of lupus nephritis in (NZB x NZW)F1 mice by allogeneic bone
      marrow transplantation.
AB  - We have recently found that allogeneic bone marrow transplantation (BMT) can be
      used to treat lupus nephritis in (NZB x NZW)F1(B/WF1), BXSB, MRL/lpr and (NZW x
      BXSB)F1 mice. To elucidate why and how glomerular damage is repaired by BMT,
      serial renal biopsies were carried out using B/WF1 mice before and after BMT.
      Donor-derived B cells and macrophages with normal functions developed two weeks
      (wks) after BMT. At this stage, the macrophages did not show immune complex (IC)
      clearance activity. Donor-derived T cells with normal functions were generated
      six wks after BMT. At this stage, visceral epithelial cells macrophages and
      mesangial cells in the glomeruli were activated by T cells and showed marked
      phagocytic activity; macrophages and mesangial cells were found to be responsible
      for the clearance of ICs, whereas, to our surprise, epithelial cells were found
      to be responsible for the repair of injured basement membranes. These findings
      suggest that T cells with normal functions, which have the capacity to activate
      macrophages, mesangial cells and epithelial cells, play a crucial role in
      repairing IC-mediated glomerular damage.

PMID- 7649565
TI  - Activation-dependent expression of low affinity IgG receptors Fc gamma RII(CD32)
      and Fc gamma RIII(CD16) in subpopulations of human T lymphocytes.
AB  - Receptors for IgG (Fc gamma R) are expressed by small subpopulations of
      peripheral blood T lymphocytes. Our studies demonstrate that T lymphocytes can be
      induced in vitro to express two different low-affinity Fc gamma R. Mitogen
      activation of peripheral blood T lymphocytes obtained from eight healthy
      individuals leads to considerable augmentation of the Fc gamma RIII+ (CD32) T
      cell subpopulation. The highest percentage of CD32 expressing T lymphocytes could
      be detected after three days of activation. The T cell subpopulation which
      transiently express the CD32 antigen, encompasses CD4+ and CD8+ cells. Molecular
      cloning of the CD32 antigen by reverse transcription and polymerase chain
      reaction demonstrates that activated human T lymphocytes express the Fc gamma
      RIIIb2 isoform. The percentage of the Fc gamma RIII+ (CD16) T cell subpopulation
      was significantly increased only in the lymphocyte populations obtained from
      three out of eight volunteers immediately after mitogen activation. However,
      during short-term cell culture the CD16 expressing CD8+ T cell subset increased
      in the T cell population from all individuals investigated. During this time, the
      IL-2 receptor alpha-chain (CD25) expression level decreased as a function of
      time. In contrast to the CD8+CD16+ T cells, the percentage of the non-MCH
      restricted CD56+CD16+ T cells was not influenced by mitogen activation and time
      of cell cultivation. We could show that CD16 in T cells is able to mediate a
      stimulus leading to proliferation of the CD8+CD56-CD16+ T cells but not that of
      the CD56+CD16+ T cell subset. This discrepancy cannot be explained by the
      expression of different Fc gamma RIII isoforms, because both T cell subsets
      express Fc gamma RIIIA alpha, as we demonstrate in this report.

PMID- 7649566
TI  - Changes of intracellular free calcium concentration in human polymorphonuclear
      leukocytes after repeated stimulations with N-formyl-methionyl-leucyl
      phenylalanine.
AB  - A rapid transient rise in the intracellular free calcium concentration ( Ca2+]i)
      is an important step in human polymorphonuclear leukocytes (PMNL) activation.
      This can be caused by many inflammatory mediators and has been implicated in the
      regulation of various cellular reactions. In this study we investigated the
      changes of [Ca2+]i in human PMNL activated three times with 10(-7)M n-formyl
      methionyl-leucyl-phenylalanine (FMLP). PMNL in the presence of 1 mM Ca2+ were
      able to respond to three consecutive stimulations with FMLP. The first Ca2+
      response was the highest one and was a result of Ca2+ release from internal
      stores (which was responsible for about 30% of maximal increment in [Ca2+]i) and
      the extracellular Ca2+ influx. Experiments with PMNL suspended in a medium
      containing 100 nM Ca2+ and pretreated with 1 nM Ni2+ (an inorganic calcium
      channel blocker) revealed that the second and third response is completely
      dependent on the extracellular Ca2+ influx. Changes of the time interval between
      stimulations had no influence on the occurrence of extracellular Ca2+ influx
      related to second addition of FMLP. Elongation of the time interval up to 30 min
      did not restore the release of Ca2+ from internal stores. It indicates the
      occurrence of dissociation of Ca2+ release from intracellular stores and
      extracellular Ca2+ influx during the second and third PMNL response to FMLP.

PMID- 7649567
TI  - Abrogation of allospecific T lymphocyte responses in swine by ultraviolet light-B
      irradiation.
AB  - Immunomodulatory effects of ultraviolet-light B (UV-B) irradiation were tested in
      pigs, using peripheral blood lymphocytes (PBL), with special emphasis on the
      generation of cytotoxic T lymphocytes (CTL). Stimulator PBL were irradiated with
      300-1100 Joules/m2 (J/m2) of UV-B (experimental group) and cultured for 24 h
      prior to being placed in mixed lymphocyte culture (MLC) to determine
      proliferative responses against alloantigens, or placed in bulk culture with
      allogeneic PBL to determine the induction of CTL. PBL that received 3000 rads
      gamma irradiation were used as controls. Proliferative alloresponses against
      gamma irradiated PBL (control group) were high, with stimulation indices (S.I.)
      ranging from 13.46 to 81.93. The generation of allospecific CTL activity was also
      high, ranging from 50.78% to 95.40%. In contrast, proliferative responses and
      generation of allospecific CTL were markedly inhibited (> 49.77%) against the
      same donor PBL irradiated with > or = 500 J/m2 UV-B. These results demonstrated
      that ultraviolet light treatment of pig PBL can reduce or prevent allospecific T
      cell proliferation as well as the generation of specific CTL, similar to results
      obtained with UV-B irradiation of lymphocytes in rodents.

PMID- 7649568
TI  - Cytotoxic effects of irradiation and deoxyguanosine on fetal thymus.
AB  - Effects of irradiation and deoxyguanosine on the fetal thymus were examined both
      in vitro and in vivo. Fetal thymi (gestation day 15) of C57BL/6 mice that had
      been irradiated (0-25 Gy) or treated with various doses of deoxyguanosine (dGuo)
      were engrafted under the renal capsules of BALB/c nu/nu mice, and the
      differentiation of T cells was investigated in the engrafted thymi or spleens of
      these mice. After in vitro treatment of fetal thymi with 1.35 mM dGuo (which was
      previously reported to be an optimal dose), T cell precursors still remained in
      some cultures, whereas 1.80 mM dGuo was highly cytotoxic not only to T cell
      precursors but also to thymic epithelial cells. In contrast, 25 Gy irradiation
      totally eliminated the T cell precursors from the fetal thymi, though the
      capacity of epithelial cells to induce T cell differentiation was retained.
      Although irradiated thymi had the capacity to induce T cell differentiation when
      assayed in an in vitro organ culture system, long-term observation of thymi
      engrafted into BALB/c nu/nu mice revealed that, if they had been irradiated (9.5
      Gy or 25 Gy), the thymi became scarred by 12 wks after their transplantation.
      Furthermore, the expression of cell interaction molecules such as ICAM-1 and MHC
      class II on the thymus stromal cells decreased after irradiation. The interaction
      molecules decreased 3 wks after 25 Gy irradiation and 7 wks after 9.5 Gy
      irradiation. The alteration in T cell subsets in the thymus (decreases in both
      double- and single- positive cells and an increase in double-negative cells)
      correlated with the decreases in the interaction molecules. This indicates that
      irradiation (even 9.5 Gy) impairs the T cell-induction capacity of the thymus
      stromal cells, resulting in an alteration of the T cell subsets followed by a
      change in the T cell counts in the thymus. Therefore, the long-term effects of
      irradiation of the thymus should be considered in cases of fetal thymus grafts or
      total body irradiation before bone marrow transplantation, particularly in the
      newborn.

PMID- 7649569
TI  - Isolated diastolic hypertension. A favorable finding among young and middle-aged
      hypertensive subjects.
AB  - To identify pretreatment characteristics associated with subsequent myocardial
      infarction in young and middle-aged previously untreated hypertensive
      individuals, we examined the experience of 1560 participants in a work-site
      hypertension control program who were younger than 60 years. Subjects were
      categorized by initial blood pressure as having isolated diastolic hypertension
      (< 160/> or = 90 mm Hg, n = 965) or combined systolic and diastolic hypertension
      (> or = 160/> or = 90 mm Hg, n = 595). During 4.5 years of follow-up, there were
      24 myocardial infarctions, yielding an overall incidence of 3.89 per 1000 person
      years. Subjects with systolic/diastolic hypertension were older, had higher
      cholesterol and blood sugar levels, and included more smokers and people with
      left ventricular hypertrophy on electrocardiogram than those with isolated
      diastolic hypertension. Age-adjusted incidence rates for myocardial infarction
      were 5.20 and 2.21 per 1000 person-years in systolic/diastolic hypertension and
      isolated diastolic hypertension, respectively, and the relative risk of
      systolic/diastolic hypertension was 2.31 (95% confidence interval, 1.29-4.15).
      Among subjects with isolated diastolic hypertension, no myocardial infarction
      occurred in those with systolic pressure less than 140 mm Hg. Cox regression
      analysis including other known risk factors showed that pulse pressure, as a
      continuous variable (hazards ratio, 1.54; 95% confidence interval, 1.08-2.20),
      and type of hypertension, ie, systolic/diastolic hypertension versus isolated
      diastolic hypertension (hazards ratio, 2.11; 95% confidence interval, 1.08-4.13),
      were independently associated with myocardial infarction. These results suggest
      that young and middle-aged treated hypertensive individuals with normal
      pretreatment systolic pressure enjoy a more favorable prognosis than do those
      with systolic elevation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7649570
TI  - Isolated elevation of diastolic blood pressure. Real or artifactual?
AB  - Not infrequently, blood pressure measurement by the standard auscultatory
      technique yields a normal systolic pressure with an elevated diastolic pressure.
      The relatively narrow pulse pressure of such a measurement raises concern about
      the accuracy of the blood pressure measurement. The purpose of this study was to
      assess the accuracy of auscultatory blood pressure measurements in patients with
      an uncommonly narrow pulse pressure, particularly patients with an elevated
      diastolic but normal systolic pressure. Auscultatory blood pressure measurements
      were compared with an objective noninvasive standard, called K2 analysis, which
      has been shown to be more accurate than the auscultatory technique. Blood
      pressure was measured simultaneously by auscultatory and K2 techniques in 175
      subjects. Comparisons were performed (1) in the group as a whole, (2) in four
      clinical subgroups (normotensive [< 140/< 90 mm Hg, n = 69], hypertensive [> or =
      140/> or = 90 mm Hg, n = 53], isolated systolic hypertensive [> or = 140/< 90 mm
      Hg, n = 38], and isolated diastolic hypertensive [< 140/> or = 90 mm Hg, n =
      15]), and (3) in two subgroups whose ratio of pulse pressure to diastolic
      pressure was greater than or equal to 0.45 (n = 151) or less than 0.45 (n = 24).
      Subjects in the isolated diastolic hypertensive group and in the group with a
      pulse pressure ratio less than 0.45 were considered to have a narrow pulse
      pressure. In the group as a whole, consistent with previous auscultatory-K2
      comparisons, systolic pressure was slightly higher and diastolic pressure
      slightly lower when measured by K2 versus the auscultatory technique
      (auscultatory, 145/85 mm Hg; K2, 147/83 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7649571
TI  - Structural and functional properties of isolated, pressurized, mesenteric
      resistance arteries from a vasopressin-deficient rat model of genetic
      hypertension.
AB  - In this study we examined the structural and functional properties of mesenteric
      resistance arteries isolated from normotensive and hypertensive vasopressin
      deficient rats. Hypertensive rats had a significantly higher mean arterial
      pressure (176 +/- 3 mm Hg) than normotensive controls (121 +/- 2 mm Hg). First-
      and second-order mesenteric resistance arteries were set up in a pressure
      myograph and pressurized to the mean arterial pressure of the rat from which they
      had been isolated. Vessels were fixed with glutaraldehyde, embedded in Araldite,
      sectioned, and examined histologically. First- and second-order mesenteric
      resistance arteries from hypertensive rats displayed a reduced internal diameter
      and increased media-to-lumen ratio compared with their normotensive controls.
      However, there was no evidence for an increased media content, indicating that
      the reduced internal diameter of hypertensive arteries was consequent to either
      remodeling of similar amounts of wall material or a reduced artery distensibility
      but not vascular growth. Pressurized arteries were also examined with respect to
      their responsiveness to the vasoconstrictors norepinephrine and arginine
      vasopressin and to the endothelium-dependent vasodilator acetylcholine and the
      endothelium-independent vasodilator papaverine. Both first- and second-order
      mesenteric arteries from hypertensive rats displayed enhanced sensitivity to
      norepinephrine compared with their normotensive controls. This effect was
      specific for norepinephrine, because responses to arginine vasopressin were
      similar in vessels isolated from normotensive and hypertensive rats. No evidence
      was found for an impaired endothelium-dependent vasodilatation in arteries from
      hypertensive rats. Indeed, in hypertensive vasopressin-deficient rats responses
      to acetylcholine were increased in first-order arteries compared with those from
      normotensive rats. Responses to papaverine were similar in arteries isolated from
      either normotensive or hypertensive rats.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7649572
TI  - Vasodilator response of mesenteric arterioles to histamine in spontaneously
      hypertensive rats.
AB  - Recent evidence suggests that spontaneously hypertensive rats (SHR) exhibit an
      impaired response to inflammatory mediators. We designed this study to analyze
      the response of arterioles of SHR after stimulation with a proinflammatory agent,
      histamine, compared with the response of arterioles of normotensive Wistar-Kyoto
      (WKY) controls. We observed mesenteric arterioles by intravital microscopy in
      rats under general anesthesia and measured their lumen diameters after histamine
      superfusion. To compare the concentration-response curve with histamine, we also
      studied the effect of an endothelium-dependent vasodilator, acetylcholine, and an
      independent vasodilator, sodium nitroprusside. At the end of each experiment we
      applied papaverine topically to determine the maximal diameter for each vessel,
      from which we computed arteriolar tone. Arteriolar tone in SHR is set at a higher
      steady state level than in WKY. The concentration required for a 50% dilator
      response (EC50) of histamine in SHR was significantly higher than that in WKY. In
      SHR the arteriolar response showed the same refractory pattern to histamine as to
      acetylcholine. In contrast, the EC50 of sodium nitroprusside in SHR was similar
      to that in WKY. Our results indicate that SHR exhibit an impaired dilator
      response to histamine that is due to a blunted endothelium-dependent
      vasodilation.

PMID- 7649573
TI  - Inhibition by cardiac natriuretic peptides of rat vascular endothelial cell
      migration.
AB  - Vascular endothelial cell migration is proposed to be an important process in the
      initiation and progression of atherosclerosis. We designed the present study to
      examine the effects of atrial and brain natriuretic peptides on fetal calf serum
      stimulated migration of cultured rat aortic endothelial cells using Boyden's
      chamber method. Fetal calf serum clearly stimulated migration in a concentration-
      and time-dependent manner. Rat atrial natriuretic peptide-(1-28) and rat brain
      natriuretic peptide-45, which are the major circulating forms of atrial and brain
      natriuretic peptides in rats, inhibited fetal calf serum-stimulated migration in
      a concentration-dependent manner between 10(-10) and 10(-6) mol/L. Such
      inhibition by these natriuretic peptides was paralleled by an increase in the
      cellular level of cGMP. The addition of a cGMP analogue 8-bromo-cGMP,
      significantly inhibited fetal calf serum-stimulated migration in a concentration
      dependent manner between 10(-7) and 10(-3) mol/L. Rat atrial natriuretic peptide
      (5-25) was much less effective than atrial natriuretic peptide-(1-28) or rat
      brain natriuretic peptide-45 with respect to inhibiting migration and increasing
      cGMP levels. These results indicate that atrial and brain natriuretic peptides
      inhibit fetal calf serum-stimulated vascular endothelial cell migration, probably
      through a cGMP-dependent process.

PMID- 7649574
TI  - Stimulation of endogenous nitric oxide pathway by L-arginine reduces declamp
      mortality and attenuates hypertension associated with aortic cross-clamp-induced
      hindlimb ischemia in rats.
AB  - We tested the hypotheses that maintaining the activity of nitric oxide by L
      arginine infusion would counteract the release of an endogenous nitric oxide
      synthase inhibitor, improve survival, and decrease intraoperative hypertension
      after infrarenal aortic cross-clamp surgery. Hindlimb ischemia was generated by
      infrarenal aortic cross-clamping and tying of the left femoral artery for 5 hours
      in rats with bilateral femoral and sciatic nerves cut. Mean blood pressure
      significantly increased during the 5-hour ischemic period in ischemic rats (no
      drug treatment). Baroreceptor function was inhibited in ischemic rats assessed by
      intravenous dose response to phenylephrine and nitroprusside after 5 hours of
      ischemia, suggesting baroreceptor resetting. In ischemic rats infused with L
      arginine the intraoperative hypertension was prevented during the 5-hour period,
      suggesting that this hypertension may be mediated by nitric oxide inhibition. The
      rates of survival and arrhythmias 2 hours after declamping were 50% in ischemic
      rats and 100% in ischemic rats treated with N omega-nitro-L-arginine (a nitric
      oxide synthase inhibitor) 10 minutes before declamping. In ischemic rats infused
      with L-arginine the survival rate was significantly increased to 100% and the
      arrhythmic rate was inhibited. We conclude that L-arginine prevents hypertension
      during cross-clamping and decreases the mortality rate and arrhythmias after
      declamping by maintaining nitric oxide synthesis. These results suggest that
      humoral factors released from the ischemic hindlimb may inhibit endogenous nitric
      oxide production, thus contributing to intraoperative hypertension, arrhythmias,
      and high mortality rate after aortic cross-clamp surgery.

PMID- 7649575
TI  - Is white coat hypertension associated with arterial disease or left ventricular
      hypertrophy?
AB  - Although white coat hypertension may be present in 20% or more of hypertensive
      individuals, its prognostic significance is unknown. We compared prognostically
      relevant measures of target-organ damage among 24 individuals with white coat
      hypertension and age- and sex-matched groups of sustained hypertensive and
      normotensive subjects classified by clinical and 24-hour ambulatory blood
      pressures. Left ventricular and carotid artery structure and function were
      evaluated by ultrasonography. Left ventricular mass index was similar in white
      coat hypertensive (82 +/- 17 g/m2) and normotensive (78 +/- 15 g/m2) subjects but
      was higher in sustained hypertensive subjects (97 +/- 19 g/m2, P < .02 and P <
      .002, respectively). Similarly, carotid artery intimal-medial thickness was
      greater in the sustained hypertensive group (0.98 +/- 0.21 mm) than in the white
      coat hypertensive (0.84 +/- 0.16 mm, P < .05) and normotensive (0.76 +/- 0.18 mm,
      P < .001) groups. The prevalence of discrete atherosclerotic plaques was higher
      in the sustained hypertensive group (58%) than in the white coat hypertensive
      (25%, P < .05) and normotensive (21%, P < .02) groups. Cardiac and carotid
      structure in individuals with white coat hypertension resemble findings in
      normotensive subjects and differ significantly from those in age- and sex-matched
      sustained hypertensive subjects. These findings suggest that white coat
      hypertension may be a benign condition for which pharmacological intervention may
      not be necessary, a hypothesis that needs to be tested in longitudinal studies
      with clinical end points.

PMID- 7649576
TI  - Chronic infusion of angiotensin II resets baroreflex control of heart rate by an
      arterial pressure-independent mechanism.
AB  - The purpose of this study was to test the hypothesis that chronic infusion of
      angiotensin II (Ang II) in rabbits resets the cardiac baroreflex to a higher
      arterial pressure level by a pressure-independent mechanism. This hypothesis was
      tested by determining whether the resetting would be reversed soon after the Ang
      II infusion was stopped even if the hypertension was maintained by infusion of
      another vasoconstrictor. Relationships between arterial pressure and heart rate
      were determined by infusion of increasing doses of nitroprusside to decrease
      pressure and increase heart rate, followed by increasing doses of phenylephrine
      to increase pressure and decrease heart rate. After 9 to 10 days of Ang II
      infusion (20 ng.kg-1.min-1) arterial pressure was increased from 62 +/- 2 to 94
      +/- 3 mm Hg (P < .001), and heart rate was unchanged from control values of 126
      +/- 7 beats per minute. The baroreflex relationship between arterial pressure and
      heart rate was shifted to a higher pressure level after 3 to 4 and 9 to 10 days
      of Ang II infusion. On these same days the Ang II infusion was replaced with
      phenylephrine (5.0 +/- 0.4 micrograms.kg-1.min-1), and 30 minutes later arterial
      pressure decreased slightly (P < .05); however, despite the relative hypotension,
      heart rate was decreased (P < .005) from 126 +/- 5 to 98 +/- 7 beats per minute
      (days 3 to 4) and from 132 +/- 4 to 103 +/- 7 beats per minute (days 9 to 10).
      Moreover, the cardiac baroreflex relationships were shifted back to a lower
      pressure level (P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7649578
TI  - Enhanced immunoglobulin formation of immortalized B cells from hypertensive
      patients.
AB  - Increased immunoglobulin levels and leukocyte counts have frequently been
      reported in essential hypertension. The underlying mechanisms, however, have
      remained obscure. Enhanced Na(+)-H+ exchanger activity is another frequently
      observed abnormality in essential hypertension that persists in immortalized B
      lymphoblasts and coincides with enhanced proliferation. We investigated the
      capacity of B lymphoblasts from essential hypertensive patients to synthesize and
      secrete immunoglobulins. Six B cell lines from essential hypertensive patients
      with enhanced Na(+)-H+ exchanger phenotype and six cell lines from normotensive
      subjects were studied. Lymphocyte markers were visualized by immunostaining.
      Immunoglobulin secretion was analyzed by enzyme-linked immunosorbent assay. These
      cell lines did not differ with respect to B cell markers. In response to 100
      nmol/L platelet-activating factor, cells from hypertensive patients proliferated
      distinctly more quickly and their cell number increased by 3.9 +/- 0.4-fold (mean
      +/- SD) within 4 days, whereas the number of cells from normotensive subjects
      increased by only 2.6 +/- 0.1-fold. Furthermore, platelet-activating factor
      induced average increases in IgM and IgG formation of 13.3- and 5.4-fold,
      respectively, in lymphoblasts from hypertensive patients, which was significantly
      higher than increases in cells from normotensive subjects (1.4- and 1.2-fold,
      respectively). Thus, lymphoblasts from hypertensive patients proliferate more
      quickly and secrete more immunoglobulins in response to a physiological stimulus
      in vitro. This may contribute to the raised immunoglobulin levels and leukocyte
      counts reported in vivo.

PMID- 7649577
TI  - Differential modulation of baroreceptor sensitivity by long-term antihypertensive
      treatment.
AB  - We investigated the effects of long-term oral treatment with four different
      classes of antihypertensive drugs (a thiazide diuretic [trichlormethiazide, 10
      mg/kg per day]; a beta-blocker [atenolol, 90 mg/kg per day]; a calcium channel
      antagonist [nicardipine, 150 mg/kg per day]; and an angiotensin-converting enzyme
      inhibitor [enalapril maleate, 10 mg/kg per day]) on aortic baroreceptor activity
      in spontaneously hypertensive rats with chronic hypertension (36 weeks of age).
      Treatment with each of the four drugs, given from 10 to 36 weeks of age,
      similarly decreased arterial pressure (171 +/- 2 to 144 +/- 1 mm Hg, P < .01) and
      similarly decreased the threshold pressure for baroreceptors (116 +/- 3 to 103 +/
      1 mm Hg, P < .05). The four antihypertensive drugs also potentiated the maximal
      gain of the pressure-activity relation in these rats (untreated, 1.08 +/- 0.05%
      maximum/mm Hg); however, nicardipine and enalapril (1.77 +/- 0.04% and 1.70 +/-
      0.06% maximum/mm Hg, respectively) augmented the maximal gain to a greater extent
      (P < .05 to .01) than did trichlormethiazide or atenolol (1.49 +/- 0.05% and 1.42
      +/- 0.02% maximum/mm Hg, respectively). When the initiation of treatment was
      delayed to 28 weeks of age, no differences were found in the effects on either
      threshold pressure (104 +/- 1 mm Hg) or maximal gain (1.36 +/- 0.03% maximum/mm
      Hg) for all four drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7649579
TI  - Comparison of perindopril and amlodipine in cyclosporine-treated renal allograft
      recipients.
AB  - The objective of this study was to compare the antihypertensive efficacy and
      influence on renal function of perindopril and amlodipine in cyclosporine-treated
      renal allograft recipients with mild to moderate hypertension. We conducted a
      randomized, double-blind, double-dummy crossover trial in ambulatory patients.
      Four phases were conducted: 2 weeks on placebo, 8 weeks of maintenance
      (perindopril or amlodipine), and 2 weeks of washout between treatment periods.
      Ten hypertensive patients with stable renal allograft function transplanted more
      than 6 months previously and receiving cyclosporine as part of their
      immunosuppressive regimen were studied. The patients were allocated to
      perindopril (2 or 4 mg/d) and amlodipine (5 mg/d) in a random sequence. If office
      diastolic pressure was greater than or equal to 90 mm Hg after 4 weeks, the
      dosage was doubled and continued for another 4 weeks. The main outcome measures
      were office and 24-hour ambulatory blood pressure changes after 8 weeks of active
      treatment and treatment and time effect on glomerular filtration rate and
      effective renal plasma flow. Perindopril and amlodipine were equally effective in
      lowering office blood pressure and similarly efficacious for the 24-hour period
      of the day. Neither drug affected glomerular filtration rate or effective renal
      plasma flow. Both agents demonstrated equivalent capacity (time x treatment, P =
      .955) to reverse renal vascular resistance (amlodipine from 0.35 +/- 0.02 to 0.30
      +/- 0.02 mm Hg/mL per minute per 1.73 m2; perindopril from 0.36 +/- 0.03 to 0.32
      +/- 0.01) (time effect of all treatments together, P = .043).(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7649580
TI  - Beta-adrenergic, angiotensin II, and bradykinin receptors enhance
      neurotransmission in human kidney.
AB  - The aim of this study was to investigate angiotensin II (Ang II) receptor-,
      bradykinin receptor-, and beta-adrenergic receptor-mediated modulation of
      norepinephrine release from human renal sympathetic nerves and to characterize
      the respective receptor subtypes involved. Human cortical kidney slices were
      incubated with [3H]norepinephrine, placed in superfusion chambers between two
      platinum electrodes, and superfused with Krebs-Henseleit solution. The
      sympathetic nerves were stimulated electrically at 2.5 Hz for 1 minute, and the
      stimulation-induced outflow of radioactivity was taken as an index of endogenous
      norepinephrine release. Ang II and its precursor Ang I (both 0.01 to 1 mumol/L)
      enhanced stimulation-induced outflow of radioactivity in a concentration
      dependent manner, with EC50 values of 0.03 and 0.05 mumol/L, respectively. The
      enhancement by Ang I but not that by Ang II was inhibited by the angiotensin
      converting enzyme inhibitor captopril (3 mumol/L). The concentration-response
      curves of Ang I and Ang II were shifted to the right by EXP 3174 (0.01 mumol),
      the in vitro active form of the Ang II type 1 receptor antagonist losartan, with
      affinity estimates of 8.72 and 9.30, respectively. A higher concentration of EXP
      3174 (0.1 mumol/L) abolished the facilitatory effects of Ang I and Ang II. The
      Ang II type 2 receptor antagonist PD 123319 (10 mumol/L) did not alter the
      facilitation by Ang II. In the absence of other drugs, bradykinin (0.01 to 1
      mumol/L) failed to modulate stimulation-induced outflow of radioactivity but in
      the presence of captopril (3 mumol/L) enhanced it in a concentration-dependent
      manner, with an EC50 of 0.1 mumol/L.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7649581
TI  - Blood pressure in genetically hypertensive rats. Influence of the Y chromosome.
AB  - We used a cross between the stroke-prone spontaneously hypertensive rat (SHRSP)
      strain and the Wistar-Kyoto (WKY) normotensive strain to elucidate the genetic
      basis of hypertension. Previous studies have reported conflicting evidence for
      the contribution of the Y chromosome to hypertension in these models. To
      investigate further the role of the Y chromosome in hypertension, we performed
      two large reciprocal crosses: one with the SHRSP as a male progenitor of the
      cross, yielding 60 F2 rats, and another with the WKY as a male progenitor,
      yielding 83 F2 rats. The resulting F2 hybrids were phenotyped with the use of a
      radiotelemetry system (Data Sciences) for measurement of systolic, diastolic, and
      mean arterial pressures as well as heart rate and motor activity continuously for
      96 hours at baseline and after 1% NaCl was added to the rats' drinking water for
      12 days. Male F2 hybrids with the SHRSP grandfather had significantly higher
      average systolic, diastolic, and mean arterial pressures at baseline compared
      with male F2 hybrids with the WKY grandfather (188.7 +/- 18.1 versus 168.9 +/-
      11.5, 130.3 +/- 14 versus 115.7 +/- 7.3, and 159.1 +/- 15.8 versus 141.5 +/- 9.4
      mm Hg, respectively). These differences were also observed after salt loading
      (197.9 +/- 22.1 versus 176.8 +/- 11.7, 136.5 +/- 17.3 versus 120.7 +/- 7.6, and
      166.7 +/- 19.5 versus 148 +/- 9.7 mm Hg, respectively; P < .0001 for each
      comparison). These results suggest that the SHRSP Y chromosome contains a locus
      or loci that contribute to hypertension in SHRSP/WKY F2 hybrids.

PMID- 7649582
TI  - Amylin stimulates plasma renin concentration in humans.
AB  - Although insulin resistance and hypertension are commonly associated, the
      underlying cause for this association remains unknown. Plasma concentrations of
      the recently described hormone amylin, which is cosecreted with insulin by the
      pancreatic beta cell, are reported to be elevated in various states of insulin
      resistance, including hypertension and obesity. Preliminary studies by our group
      have suggested that there are amylin binding sites in the kidney. In nine healthy
      humans an infusion of human amylin that resulted in steady state plasma amylin
      levels in the subnanomolar range led to significant increases in plasma renin and
      aldosterone concentrations. These changes occurred in the absence of significant
      changes in plasma electrolytes, catecholamines, vasopressin, total renin, or
      osmolality. Diastolic pressure at 30 minutes and plasma glucose at 60 minutes
      rose modestly. Since amylin has both metabolic and renal actions, this peptide
      may be an important link between hypertension, insulin resistance, and the renin
      angiotensin system.

PMID- 7649583
TI  - Hemodynamic alterations in hypertensive obese rabbits.
AB  - There is little information on changes in overall and regional hemodynamics in
      obesity-associated hypertension. Therefore, the purpose of this study was to
      determine alterations in overall and regional blood flows and resistances in
      adipose and nonadipose tissues in a new model of obesity-associated hypertension
      in rabbits. Sixteen female New Zealand White rabbits were fed either a
      maintenance or high-fat diet; after 8 to 12 weeks cardiac output and regional
      blood flows were measured with the use of radioactive microspheres. Obese rabbits
      (5.22 +/- 0.14 versus 3.66 +/- 0.04 kg) had higher blood pressure (113 +/- 3
      versus 95 +/- 1 mm Hg), cardiac output (812 +/- 59 versus 593 +/- 47 mL/min), and
      heart rate (269 +/- 12 versus 219 +/- 9 beats per minute) and lower overall
      peripheral resistance (0.14 +/- 0.01 versus 0.17 +/- 0.01 mm Hg/[mL/min]) than
      lean rabbits. Compared with lean controls, obese rabbits had higher weights of
      the ventricles, kidneys, liver, ovaries, adrenals, diaphragm, and spleen.
      Absolute blood flows were greater in the ventricles, kidneys, lungs, and ovaries,
      but differences were minimized when flows were normalized for organ weight.
      Adipose tissue flow per gram weight was significantly lower and resistance higher
      in obese rabbits. However, calculated total adipose tissue flow was higher in
      obese rabbits (86 versus 45 mL/min). Absolute resistances were lower in the left
      ventricle, kidneys, and large intestine, but when resistances were indexed for
      organ weight, kidney resistance tended to be higher in obese rabbits. These
      results indicate that even short periods of obesity-associated hypertension
      result in marked overall and regional hemodynamic changes.

PMID- 7649584
TI  - Effect of captopril and angiotensin II receptor blockade on pressure natriuresis
      in transgenic TGR(mRen-2)27 rats.
AB  - The pressure-natriuresis curve of transgenic rats harboring an extra mouse renin
      gene [TGR(mRen-2)27] is shifted rightward compared with controls; however,
      whether intrarenal angiotensin II effects are responsible for the rightward shift
      is unknown. To clarify this issue we infused the converting enzyme inhibitor
      captopril or the angiotensin II receptor blocker CV 11974 into transgenic and
      normotensive Sprague-Dawley Hannover control rats. We eliminated any other neural
      or endocrine regulatory differences between transgenic and control rats by renal
      denervation and infusion of vasopressin, aldosterone, corticosterone, and
      norepinephrine in sufficient quantities to occupy all receptors. Sodium excretion
      increased from 3.4 +/- 1.2 to 10.1 +/- 0.5 mumol/min per gram kidney weight in
      transgenic rats when renal perfusion pressure was increased from 158 to 201 mm
      Hg. Captopril (4 mg/kg) and CV 11974 (0.1 mg/kg) shifted the pressure-natriuresis
      curve of transgenic rats leftward, so that sodium excretion was threefold higher
      at similar renal perfusion pressures (150 to 160 mm Hg). Similarly, fractional
      sodium and water excretion curves were shifted leftward, so that values for
      transgenic and control rats were no longer different. Over the pressure range,
      renal blood flow in transgenic rats ranged from 3.1 +/- 0.7 to 4.4 +/- 0.5 mL/min
      per gram kidney weight and increased (P < .05) with both captopril and CV 11974
      to ranges from 4.8 +/- 0.9 to 6.8 +/- 0.6 or from 4.5 +/- 0.7 to 6.9 +/- 1.0
      mL/min per gram kidney weight, respectively. Glomerular filtration rate in
      transgenic rats, on the other hand, was not increased. Transgenic kidneys showed
      severe hypertension-induced nephrosclerosis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7649585
TI  - Neuropeptide Y prevents agonist-stimulated increases in contractility.
AB  - Neuropeptide Y has been shown to inhibit contractility in the rat heart. Although
      the reasons for this effect are not known, it is possible that postsynaptic
      adrenergic mechanisms involving neuropeptide Y may be responsible. To ascertain
      whether this neuromodulatory effect is possible for decreasing contractility, we
      investigated the effect of neuropeptide Y on agonist-stimulated contractility of
      the isolated rat myocardium. Receptor binding studies of purified cardiac
      membranes showed that incubating membrane in the presence of neuropeptide Y (10(
      7) mol/L) decreased the number of alpha-/beta-adrenoceptor binding sites without
      affecting the affinity of these receptors. Isolated hearts perfused with
      phenylephrine (10(-5) to 10(-10) mol/L) or isoproterenol (10(-5) to 10(-10)
      mol/L) in a nonrecirculating Langendorff setup demonstrated a significant
      increase in contractility over control values, whereas no change in contractility
      was observed when the hearts were perfused with neuropeptide Y (10(-7) mol/L).
      However, in the presence of both agonist and neuropeptide Y the increase in
      contractility previously seen with agonist alone was not evident. Comparisons
      made with hearts taken from aortic banded rats yielded similar results. Although
      neuropeptide Y itself was ineffective in decreasing contractility, it prevented
      the agonists from stimulating contractility when perfused together. We conclude
      that neuropeptide Y does not directly decrease contractility but prevents agonist
      stimulated increases in contractility through alpha-/beta-adrenoceptor pathways.
      This neuromodulatory effect of neuropeptide Y is unchanged in situations of
      increased sympathetic activity, such as hypertension.

PMID- 7649586
TI  - Assessment of arterial distensibility by automatic pulse wave velocity
      measurement. Validation and clinical application studies.
AB  - Pulse wave velocity is widely used as an index of arterial distensibility. The
      aim of this study was to evaluate the accuracy of a new automatic device to
      measure it and then to analyze the major determinants of pulse wave velocity by
      application of this device in a large population. We evaluated the accuracy of on
      line and computerized measurement of pulse wave velocity using an algorithm based
      on the time-shifted and repeated linear correlation calculation between the
      initial rise in pressure waveforms compared with the reference method (manual
      calculation) in 56 subjects. The results, analyzed according to the
      recommendations of Bland and Altman, showed a mean difference of -0.20 +/- 0.45
      m/s for the mean carotid-femoral pulse wave velocity values (reference method,
      11.05 +/- 2.58 m/s; automatic device, 10.85 +/- 2.44 m/s). The
      interreproducibility and intrareproducibility of measurements by each method were
      analyzed with the use of the repeatability coefficient according to the British
      Standards Institution. The interobserver repeatability coefficient was 0.947 for
      the manual method and 0.890 for the automatic, and intraobserver repeatability
      coefficients were 0.938 and 0.935, respectively. We evaluated the major
      determinants of the carotid-femoral pulse wave velocity measured by the automatic
      method in a separate study performed in 418 subjects of both sexes without any
      cardiovascular treatment or complication (18 to 77 years of age; 98 to 222 mm Hg
      systolic and 62 to 130 mm Hg diastolic pressure).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7649587
TI  - Angiotensin-converting enzyme inhibition and radial artery compliance in patients
      with congestive heart failure.
AB  - Congestive heart failure is characterized by a clear-cut impairment of arterial
      compliance of medium-sized arteries, but whether this alteration is irreversible
      or can be favorably affected by cardiovascular drugs currently used in congestive
      heart failure treatment is unknown. We studied 9 congestive heart failure
      patients (New York Heart Association class II; age, [mean +/- SEM] 60.7 +/- 3.3
      years) receiving diuretic and digitalis treatment in whom arterial compliance was
      assessed at the level of the radial artery by an echotracking device capable of
      measuring the arterial diameter along the entire cardiac cycle. Beat-to-beat
      arterial blood pressure was concomitantly measured by a Finapres device that
      allowed diameter-pressure curves and compliance-pressure curves (Langewouters'
      formula) to be calculated for the entire systolic-diastolic blood pressure range.
      Arterial compliance was expressed as the area under the compliance-pressure curve
      normalized for pulse pressure (compliance index). Data were collected before and
      after 4 and 8 weeks of oral administration of benazepril (10 mg/day). Ten healthy
      subjects were studied before and after an observational period of 4 weeks (5
      subjects) or 8 weeks (5 subjects), and 9 age-matched mildly essential
      hypertensive subjects studied before and after 4 to 12 weeks of benazepril
      administration served as control subjects. In congestive heart failure patients,
      baseline compliance index was significantly less than in normotensive and
      hypertensive subjects. However, the compliance index showed a marked increase
      after 4 weeks of benazepril administration (+95.7 +/- 24.9%, P < .05); the
      increase was also marked after 8 weeks of angiotensin-converting enzyme inhibitor
      treatment (+77.7 +/- 4.2%, P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7649588
TI  - Postischemic blood flow response in hypercholesterolemic patients.
AB  - We undertook this cross-sectional study to compare the mechanical behavior and
      postischemic response of the radial artery of 15 newly diagnosed
      hypercholesterolemic patients with those of 15 age- and sex-matched
      normocholesterolemic control subjects and 21 hypercholesterolemic patients
      treated for 2 years with an 3-hydroxy-3-methylglutaryl coenzyme A reductase
      inhibitor (simvastatin, 10 to 20 mg/d). At the time of the study total
      cholesterol levels were at 7.9 +/- 0.2, 4.9 +/- 0.2, and 6.0 +/- 0.3 mmol/L in
      the three groups, respectively (mean +/- SEM, P < .001). High-resolution,
      noninvasive echotracking for assessment of internal arterial diameter was
      combined with measurements of blood flow velocity by Doppler and blood pressure
      by photoplethysmography. Radial cross-sectional compliance and distensibility
      were similar in all groups. Forearm blood flow and flow-mediated dilation were
      measured after a 5-minute upper arm occlusion. Flow was calculated from the
      vessel diameter and blood flow velocity recorded simultaneously at the same site.
      Flow-mediated dilation after ischemia was not significantly different among the
      three groups. However, forearm blood flow increase was markedly blunted (P < .01)
      in untreated hypercholesterolemic patients (211%) compared with the
      normocholesterolemic control subjects (411%) and treated patients (365%). These
      findings suggest that the distensibility of the radial artery, a muscular conduit
      vessel usually devoid of atherosclerotic lesions, and its flow-mediated dilation
      are preserved in hypercholesterolemic patients. In contrast, forearm resistance
      vessels exhibit a markedly reduced postischemic blood flow response that may be
      restored by prolonged lipid-lowering intervention.

PMID- 7649589
TI  - Noninvasive pulse wave analysis for the early detection of vascular disease.
AB  - A noninvasive technique has been developed and validated for calculating
      capacitive and oscillatory systemic arterial compliance with the use of pulse
      wave analysis and a modified Windkessel model. Application of the technique to
      subjects with hypertension, postmenopausal women with symptomatic coronary artery
      disease, and appropriate control subjects has confirmed a reduction of
      oscillatory compliance in the disease states and an increase in capacitive and
      oscillatory compliances in response to vasodilator drugs. This method should be
      useful in screening subjects for early evidence of vascular disease and in
      monitoring the response to therapy.

PMID- 7649590
TI  - Sick vessel syndrome. Recovery of atherosclerotic and hypertensive vessels.
AB  - This review describes vascular changes in atherosclerotic and hypertensive
      vessels as well as effects of treatment. Changes in vascular structure in both
      atherosclerosis and hypertension are characterized by thickening of the vessel
      wall and vascular "remodeling." Remodeling tends to preserve the size of the
      lumen in atherosclerotic vessels and results in a smaller lumen in hypertensive
      vessels. Changes in vascular function are characterized by preservation of smooth
      muscle relaxation, with the exception of activity of ATP-sensitive potassium
      channels, and dysfunction of endothelium. Regression of atherosclerosis, by
      treatment of hyperlipidemia, results in quite rapid removal of lipid from the
      vessel wall but with inconsistent improvement in maximal vasodilator capacity. In
      contrast, endothelial function improves during regression of atherosclerosis, and
      hyperresponsiveness to serotonin subsides rapidly. Effective treatment of
      hypertension produces regression of vascular hypertrophy, and some approaches
      (especially angiotensin-converting enzyme inhibitors) are effective in correcting
      vascular remodeling. Endothelium-dependent relaxation generally improves during
      antihypertensive treatment. Reduction in pulse pressure may be more important
      than reduction in mean arterial pressure in reversing the structural and
      functional abnormalities of hypertensive vessels.

PMID- 7649591
TI  - Influence of sex on arterial hemodynamics and blood pressure. Role of body
      height.
AB  - Systolic pressure is lower in premenopausal women than in age-matched men, but
      underlying alterations are not well characterized. Aging and body size alter
      arterial function, influencing pressure wave propagation and amplification in
      peripheral and central arteries. To assess the possibility that systolic pressure
      differences in women are related to smaller body size, we studied arterial
      function in 119 men and 104 women. Premenopausal and postmenopausal women were
      compared with age-matched men. The following parameters were measured: ankle-arm
      pressure index (Doppler), aortic and arterial distensibility (pulse wave
      velocity), systolic pressure and the effect and time delay of arterial wave
      reflections in the common carotid artery (applanation tonometry), and diameters
      of the abdominal aorta and aortic bifurcation and their ratio (aortic tapering,
      echography). Premenopausal women had lower brachial (P < .05) and ankle (P < .01)
      systolic pressures than age-matched men, whereas the ankle-arm pressure index was
      higher in men (P < .01). In the overall population the ankle-arm index was
      positively correlated with body height (P < .001). Carotid systolic pressure was
      similar in women and men, with an increased effect and earlier return of wave
      reflections in women (P < .01). The effect of wave reflections was inversely
      correlated with body height (P < .001) and positively associated with aortic
      tapering (P < .001), which was increased in women (P < .01). In premenopausal
      women the distensibility of brachial and femoral arteries was higher than in age
      matched men (P < .01), whereas aortic distensibility was not different.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7649592
TI  - Underestimation of vasodilator effects of nitroglycerin by upper limb blood
      pressure.
AB  - To determine why upper limb blood pressure measurement underestimates the
      vasodilator effects of nitroglycerin on lowering ascending aortic systolic
      pressure, we studied 24 patients (58 +/- 11 years, mean +/- SD). Ascending aortic
      pressure and radial artery pulse calibrated by cuff blood pressure measurement at
      the brachial artery were recorded simultaneously before and 5 minutes after
      sublingual administration of 0.3 mg nitroglycerin. Waves were analyzed by a
      signal processor, and the fourth derivative wave was used to find the early (S1)
      and late (S2) systolic shoulders (S1 corresponds to the second zero crossing and
      S2 to the third zero crossing). Before nitroglycerin administration, maximal
      systolic pressure in the ascending aorta (141 +/- 21 mm Hg) coincided with the
      late systolic peak in all patients, and in most patients (21 of 24) maximal
      systolic pressure in the radial artery (140 +/- 19 mm Hg) coincided with the
      early systolic peak. Maximal systolic pressure decreased more in the ascending
      aorta than in the radial artery (22 +/- 13 and 11 +/- 11 mm Hg, respectively; P <
      .001). However, the reduction in the shoulder of late systolic pressure in the
      radial artery (24 +/- 13 mm Hg) clearly indicated the reduction in maximal
      systolic pressure (late systolic peak) in the ascending aorta. The augmentation
      index of the ratio of the height of late systolic pressure to early systolic
      pressure fell proportionally (r = .74, P < .001) in the radial artery (from 0.88
      +/- 0.13 to 0.60 +/- 0.11) and in the ascending aorta (from 1.57 +/- 0.25 to 1.26
      +/- 0.24), which indicated the reduction in late systolic pressures.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7649593
TI  - Short- and long-term effects of antihypertensive drugs on arterial reflections,
      compliance, and impedance.
AB  - This article reviews our work on the effects of different classes of
      antihypertensive agents on the hemodynamic alterations in essential human
      hypertension. Short-term studies were done during cardiac catheterization in
      young normotensive subjects (mean age, 33 years; range, 19 to 40) and several
      different age-matched (range, 25 to 53 years) groups of patients with essential
      hypertension. Aortic impedance, resistance, wave reflections, and compliance were
      calculated from high-fidelity recordings of ascending aortic pressure and flow
      signals during baseline and after nitroprusside, propranolol followed by
      phentolamine, phentolamine, captopril, and nifedipine, respectively, at doses
      sufficient to normalize blood pressure in each hypertensive group. Propranolol
      exacerbated all the hemodynamic parameters; these effects were only partially
      overcome by phentolamine. Among the other agents only phentolamine did not
      completely normalize compliance, and only captopril did not completely normalize
      wave reflections. The long-term study was a randomized, double-blind comparison
      of fosinopril and atenolol in 79 normotensive subjects and 79 essential
      hypertensive patients. Baseline 24-hour ambulatory blood pressures and carotid
      artery tonometry to index wave reflections were performed in all subjects and in
      hypertensive patients after 8 weeks of therapy. Both fosinopril and atenolol
      normalized blood pressure and lowered the elevated augmentation index, but
      fosinopril had a significantly larger effect than atenolol. Both short- and long
      term beta-blockade did not have as beneficial an effect as the other agents.
      Thus, the differing hemodynamic effects of the various classes of
      antihypertensive agents might be a consideration in the choice of therapy.

PMID- 7649594
TI  - Effects of antihypertensive agents on local arterial distensibility and
      compliance.
AB  - Distensibility and compliance are important vessel wall properties.
      Distensibility is related to elastic properties of the arterial wall, and
      compliance reflects the buffering function of the artery. Distensibility is a
      determinant of stress on the vessel wall. A decreased distensibility might
      increase the risk of arterial wall damage. Therefore, a preserved local
      distensibility might be important in protecting the arterial wall of each
      particular artery and especially of those arteries that are more susceptible to
      vascular disease. Local distensibility and compliance of various large arteries
      can be measured noninvasively with echo tracking techniques. Studies on local
      distensibility and compliance revealed that with the calcium antagonist verapamil
      and the angiotensin-converting enzyme inhibitor perindopril arterial compliance
      increased mainly because of an increase in distensibility, with only a minor
      effect on arterial diameter. In contrast, the nitrate compound isosorbide
      dinitrate increased compliance mainly by increasing arterial diameter, without an
      increase in distensibility. This indicates that an increase in arterial
      compliance does not automatically imply an increase in arterial distensibility.
      The effect of antihypertensive drugs may also depend on the vascular territory.
      The diuretic amiloride/hydrochlorothiazide increased brachial artery compliance
      but not common carotid artery compliance. During angiotensin-converting enzyme
      inhibition the effect on arterial compliance was smaller at the carotid than the
      femoral artery. However, the opposite held for the nitrate compound. These
      distinctive effects of antihypertensive drugs on arterial distensibility and
      compliance and on vascular territories may be relevant to pharmacological
      prevention and management of arterial disease.

PMID- 7649595
TI  - Effect of Ajmaloon on the baroreceptor-heart rate reflex in anaesthetized rabbits
      and monkeys.
AB  - The effects of a herbal drug, Ajmaloon (Hamdard, India), on the arterial blood
      pressure, heart rate (HR) and baroreceptor-heart rate reflex were studied in
      anesthetized rabbits and monkeys. Intravenously administered Ajmaloon produced a
      dose-dependent hypotensive response in both the species without any significant
      effect on the heart rate. Only in high doses (200 mg/kg or more). Ajmaloon
      produced a bradycardia response in rabbits. Even the highest dose (300 mg/kg) of
      Ajmaloon used in the present investigation did not cause arrhythmia or any other
      conduction disorder or respiratory distress. Baroreflex SAP-HR curve was shifted
      to the left of the control following treatment with 100 mg/kg intravenous
      Ajmaloon in both the species. Loss of tachycardia response to fall in arterial
      pressure in Ajmaloon treated animals indicated the drug induced suppression of
      normally existing sympathetic excitatory influence in response to hypotension.
      Baroreflex regulatory HR response to hypertension remains intact after
      intravenous administration of 100 mg/kg Ajmaloon, a dose much higher than the
      prescribed highest oral dose for humans. Intact baroreflex regulation of arterial
      blood pressure in response to hypertension in Ajmaloon treated mammals suggests
      that in patients besides lowering the blood pressure. Ajmaloon might not
      interfere with the normal blood pressure regulatory mechanism through arterial
      baroreceptors during hypertension.

PMID- 7649596
TI  - Effect of Sahaja yoga practice on stress management in patients of epilepsy.
AB  - An attempt was made to evaluate the effect of Sahaja yoga meditation in stress
      management in patients of epilepsy. The study was carried out on 32 patients of
      epilepsy who were rendomly divided into 3 groups: group I subjects practised
      Sahaja yoga meditation for 6 months, group II subjects practised postural
      exercises mimicking Sahaja yoga and group III served as the epileptic control
      group. Galvanic skin resistance (GSR), blood lactate and urinary vinyl mandelic
      acid (U-VMA) were recorded at 0, 3 and 6 months. There were significant changes
      at 3 & 6 months as compared to 0 month values in GSR, blood lactate and U-VMA
      levels in group I subjects, but not in group II and group III subjects. The
      results indicate that reduction in stress following Sahaja yoga practice may be
      responsible for clinical improvement which had been earlier reported in patients
      who practised Sahaja yoga.

PMID- 7649597
TI  - Identification of voltage-sensitive calcium channels in Setaria cervi (Nematoda:
      Filarioidea) and their role in regulation of spontaneous motility.
AB  - Whole worm of Setaria cervi and its nerve muscle preparation exhibit rhythmical
      movements when suspended in modified Ringer's solution in an isolated organ bath.
      Deprivation of calcium from the bathing fluid results in gradual reduction in the
      amplitude and rate of contraction till the movements ceased completely. Similar
      results were obtained by adding EDTA (5 micrograms/ml) to the bath. The effect
      was concentration related and was evident early with higher concentration of
      EDTA. Acetylcholine which increases spontaneous movements of the whole worm as
      well as N.M. preparation failed to do so when the movements were inhibited either
      in calcium free solution or in the presence of EDTA. Addition of calcium channel
      blocker, Nifedipine to the bathing fluid also resulted in concentration related
      reduction of movements of the preparation of Setaria. Further, the stimulant
      response of Ach was also reduced by Nifedipine and this too was related to the
      concentration of calcium channel blocker in the bath. The evidence clearly
      indicates that presence of calcium is essential for the stimulant response of Ach
      on S. cervi, which like mammalian tissues contain calcium channels that can be
      blocked by specific blocking agents.

PMID- 7649598
TI  - Aminophylline alters pharmacokinetics of carbamazepine but not that of sodium
      valproate--a single dose pharmacokinetic study in human volunteers.
AB  - Pharmacokinetic interaction of aminophylline with single dose sodium valproate
      (400 mg) and carbamazepine (200 mg) was evaluated in normal healthy volunteers
      using a cross over design. Neither the serum concentrations nor the
      pharmacokinetic parameters of sodium valproate (SV) were altered by the
      coadministration of aminophylline (AMP). In contrast AMP significantly decreased
      the plasma concentrations of carbamazepine (CBZ). The Cmax of CBZ was
      significantly lowered from 1.73 +/- 0.18 to 0.94 +/- 0.08 microgram/ml and the
      AUC o-t was significantly decreased from 76.19 +/- 6.20 to 52.66 +/- 1.84
      micrograms/h/ml (P < 0.05). The pharmacokinetic parameters of CBZ that were
      altered in the presence of AMP were: the Tmax and t1/2 which was prolonged about
      threefold from 5.60 +/- 1.60 to 16.80 +/- 7.94 h and 44.88 +/- 4.50 to 125.07 +/-
      29.09 h, respectively. The Vd was marginally increased from 2.19 +/- 0.13 to 3.85
      +/- 0.57 L/kg and the Cl was decreased from 34.07 +/- 3.78 to 25.26 +/- 5.15
      mL/min. None of these alterations are statistically significant. Bioavailability
      of CBZ was reduced by 29% in the presence of AMP, while that of SV was increased
      by about 8%. Results are of clinical significance because simultaneous
      administration of CBZ and AMP may reduce the efficacy of CBZ in epileptic
      patients.

PMID- 7649599
TI  - Study of colour blindness in Jat Sikhs.
AB  - Of the 1306 male and 791 female Jat Sikhs of Patiala city and the surrounding
      villages between the age group 10-60 years, 50 males and one female were found to
      be having colour blindness, showing an incidence of 3.83% and 0.13% respectively.
      The study was done with the help if Ishihara Charts and Pickford Nicolson's
      anomaloscope. The type of colour blindness in males in its descending order of
      occurrence was simple deutranomaly 0.92%, extreme deutranomaly 0.77%, protanopia
      0.69%, simple protanomaly 0.61%, deutranopia 0.61%, extreme potanomaly 0.15% and
      tritanopia 0.08%. The sole colour blind female was simple deutranomaly type. The
      incidence and type of colour blindness found in males are within the range of
      other Indian samples. Nevertheless the incidence is much lower than the values
      reported in other European populations.

PMID- 7649600
TI  - Aspirin by virtue of its acidic property may act as teratogen in early chick
      embryo.
AB  - Aspirin (acetylsalicyclic acid) was dissolved either in normal saline or in
      phosphate buffer and was used in two doses to find out whether teratogenic
      potential of aspirin in chick blastoderm model is due to its acidic property or
      due to drug action. Drug was injected sub-blastodermally by window technique in
      fresh embryonated eggs after 17 hours of incubation at 39 degrees C. Eggs were re
      incubated and harvested at 40 hours. Normal development of embryos was seen with
      normal saline and percentage of normal embryos with 30 micrograms (pH-3.19) and
      120 micrograms (pH-2.64) aspirin was 31.7 and 4.9 respectively. Buffer produced
      80.8% normal embryos and buffered 30 micrograms (pH-6.87) and 120 micrograms (pH
      6.69) aspirin produced 67.7% and 30.8% normal embryos respectively. Changing the
      pH of aspirin to near neutral decreased the defect induced by aspirin but a
      significant effect of aspirin was observed at higher dose which could be
      independent of pH action.

PMID- 7649601
TI  - PEFR in pregnancy: a longitudinal study.
AB  - Peak expiratory flow rates (PEFR) were measured in 60 pregnant women aged 20-28
      years (average 24 yrs) height between 130-160 cm (average 154.5 cm), each month
      beginning from 3rd month of gestation and also 8-10 weeks postpartum using,
      Wright's Peak Flow Meter. The PEFR declined from 329.12 +/- 4.40 lpm in 3rd month
      to 286.22 +/- 3.81 lpm in 9th month of gestation and increased to 347.86 +/- 2.93
      lpm in postpartal period. A similar, declining trend is also observed in other
      Indian studies. However, the values are lower than those observed in Europeans.
      Also no change in PEFR during pregnancy was observed in an European study. The
      PEFR in our study regressed at a rate of 6.68 lpm/month of gestation and 5.49
      lpm/kg increase in weight throughout pregnancy. The correlation with forced vital
      capacity (FVC) and forced expiratory volume in first second (FEV1) is non
      significant throughout pregnancy. The anaemic pregnant women showed lower PEFR
      when compared with PEFR of nonanaemic pregnant women, but showed a similar
      declining trend throughout pregnancy.

PMID- 7649602
TI  - Involvement of K+ channels in the relaxant responses to various agonists in
      estrogen primed rat uterus.
AB  - The present investigation was undertaken to study the effects of K+ channel
      openers in the relaxant responses to various agonists in estrogen primed rat
      uterus. Adrenaline and isoprenaline produced a dose-dependent relaxation in the
      estrogen primed rat uterus. The relaxant responses were found to be significantly
      potentiated when the preparations were exposed to PSS devoid of calcium. The
      responses to isoprenaline were found to be greater in the preparations
      depolarized with 40 mM KCl instead of 80 mM KCl. KCl failed to produce any
      contractile effect in the presence of D-600. Further, the addition of D-600
      completely relaxed the KCl depolarized rat uterus. Pinacidil and cromakalim
      failed to relax 80 mM KCl depolarized rat uterus. However, they produced dose
      dependent relaxation in the preparations depolarized with 40 mM KCl. The relaxant
      responses to pinacidil and cromakalim were competitively blocked by procaine.
      However, they were not altered by either propranolol or cimetidine. The relaxant
      responses to isoprenaline and histamine were found to be potentiated by pinacidil
      and cromakalim. These results indicate that in rat uterus in addition to
      adenylate cyclase c-AMP, potassium channels are also involved in the relaxant
      responses to isoprenaline and histamine.

PMID- 7649603
TI  - Biochemical studies on the effect of S-1,3-butanediol of diabetes induced rats.
AB  - The biochemical effect of S-1,3-butanediol on streptozotocin induced diabetic
      rats was studied. Rats were made diabetic by the intraperitoneal injection of 40
      mg/kg body weight streptozotocin in sodium citrate buffer. A dosage of 25 mmol/kg
      body weight of S-1,3-butanediol was injected intraperitoneally for treatment. The
      streptozotocin induced diabetic rats showed a marked increase in blood glucose
      level, and significant increase in the level of cholesterol, triglycerides and
      free fatty acids. The glycogen levels in liver and kidney were greatly decreased
      in diabetic rats. Treatment with butanediol normalised the glucose and glycogen
      level but had no significant effect on protein and lipid levels.

PMID- 7649604
TI  - Sympathetic skin response and autonomic dysfunction in diabetes.
AB  - Study was conducted on 34 middle aged (35-52 years) diabetics of either sex to
      compare autonomic function in patients having and not having symptoms of
      dysautonomia. Fifteen age/sex matched healthy non-diabetic volunteers were
      control. No symptom of autonomic insufficiency was present in 19 (55.8%) while 15
      (43%) diabetics had dysfunction in form of episodic syncope, vertigo, and
      palpitation, all on postural change. Tests of autonomic functions were restricted
      to evaluation of salivation, lacrimation, sweating, pilomotor response, reflex
      erythema and blood pressure changes with valsalva, posture and cold pressor. SSR
      was elicited using 5 stimuli on programmed Neuropack II and IV model machine. In
      asymptomatic diabetics, tests of autonomic functions were normal and comparable
      to controls but SSR was not recordable in 8 (42%). In remaining 11 (58%)
      asymptomatic diabetics, it was recordable. In 15 subjects who had symptoms of
      autonomic dysfunction, 6 (40%) had positive test of autonomic function but SSR
      was normal in only 5 (34%) and not recordable in 10 (66%) subjects. We conclude
      that SSR can be used as a easy, sensitive and probably early indicator of
      autonomic functions.

PMID- 7649605
TI  - Pharmacodynamic interactions of cypermethrin and centrally acting drugs in mice.
AB  - Cypermethrin a widely used insecticide of Pyrethroids (type II) group, was
      administered in mice at two dose levels (1/10 of LD50 i.e. 2.5 mg/kg and 1/5 of
      LD50 i.e. 5.0 mg/kg) and pharmacodynamic interactions of insecticide were studied
      with centrally acting drugs viz. pentobarbital sodium, amphetamine,
      pentylenetetrazole, acepromazine and analgin. Cypermethrin pretreatment
      potentiated the actions of pentobarbital and pentylene-tetrazole as evidenced by
      an increase in pentobarbital induced hypnosis and duration of pentylene-tetrazole
      induced chemoshock seizures. Tranquilizing action of acepromazine was potentiated
      but there was decrease in amphetamine influenced locomotor activity at both the
      dose levels. Cypermethrin pretreatment, however, did not have any pharmacodynamic
      interaction with analgin.

PMID- 7649606
TI  - Peptidergic mechanisms in feeding behaviour.
AB  - Hyperphagia was induced in mice by p.o. administration of different types of CNS
      depressant drugs, like chlordiazepoxide 25 mg/kg diazepam 2.5 mg/kg,
      cyproheptadine 2 mg/kg and phenobarbitone 25 mg/kg. Such hyperphagia was
      abolished by pretreatment with naloxone 0.1 mg/kg sc. Naloxone per se at this
      dose produced no significant effect on the food intake. This is suggestive of the
      role of peptidergic mechanisms in the feeding behaviour in mice.

PMID- 7649607
TI  - Airway functions in pregnant Indian women.
AB  - The airway functions in pregnancy have been widely studied but reports obtained
      from Western and Indian population show divergence. While the Indian populations
      show significant changes in total and timed vital capacity (FVC and FEV1), the
      Western counterparts dismiss such changes as insignificant. Our results show
      insignificant alteration in airway function and support the results reported for
      Western population.

PMID- 7649608
TI  - Evaluation of antimuscarinic activity in human volunteers: a teaching aid in
      clinical pharmacology.
AB  - The antimuscarinic activity of oxyphenonium bromide, diphenhydramine
      hydrochloride and astemizole were evaluated in six volunteers. The parameters
      used were salivary secretion, heart rate and pupillary size. The results
      indicated that the changes in heart rate and pupillary size and measurements were
      not convenient parameters for class room demonstration. However, salivary
      secretion and dryness of mouth were found to be reliable parameters for
      measurement. It was concluded that simple procedures like evaluation of
      antimuscarinic activity could be introduced as teaching aids in clinical
      pharmacology for undergraduate students.

PMID- 7649609
TI  - Synthesis and in vivo hypoglycemic screening studies on some life essential metal
      complexes of oral antidiabetic [N-(p-tolylsulphonyl)-N'-n butyl-urea]
      (tolbutamide).
AB  - Present communication deals with the synthesis of complexes of [N-(p
      tolylsulphonyl)-N'-n butyl-urea], with certain transition metals viz. Cu(II),
      Zn(II), Fe(II) and Cd(II). Structures of all the complexes have been established
      on the basis of their consistent elemental and spectral analysis. Also, it
      reports their in vivo hypoglycemic screening on albino rats. Out of all the
      complexes studied, Zn-Tolbutamide complex could be recommended as more potent
      hypoglycemic agent in lieu of tolbutamide alone.

PMID- 7649610
TI  - Anti-inflammatory and diuretic activity of a new class of compounds--Schiff bases
      of 3-amino-2-methylquinazolin 4(3H)-ones.
AB  - Eighteen Schiff Bases of 3-amino-2-methylquinazolin-4(3H)-ones were synthesised
      and screened for anti-inflammatory and diuretic activity. Anti-inflammatory
      activity was identified in PNG-1, PNG-13, PNG-14, PNG-15 and PNG-17.

PMID- 7649611
TI  - Effect of Trigonella foenum graecum (Fenugreek) on blood glucose in normal and
      diabetic rats.
AB  - Trigonella foenum graecum (Fenugreek) was administered at 2 and 8 g/kg dose
      orally to normal and alloxan induced diabetic rats. It produced a significant
      fall (P < 0.05) in blood glucose both in the normal as well as diabetic rats and
      the hypoglycemic effect was dose related.

PMID- 7649612
TI  - Karl Friedrich Wilhelm Ludwig (1816-1895)

PMID- 7649613
TI  - Apoptosis in health and disease.
AB  - Two distinct forms of cell death are known, necrosis which results from physical
      or chemical insult and apoptosis or programmed cell death results from
      programming within the cell for self destruction in response to internal and
      external stimuli. Apoptosis is a genetically governed process of cell death
      occurring in development and maintenance of multicellular organisms. It occurs to
      get rid of individual cells that become unwanted for various reasons or that
      present a threat to the organism. It is accompanied by distinct morphological
      changes. DNA fragmentation in most cases, and appears to be caused by the
      activities of specific genes. Its defective regulation may play a part in the
      aetiology of cancer, AIDS, autoimmune and degenerative diseases. Apoptosis offers
      potential for prevention and therapeutic modulation of these disorders.

PMID- 7649614
TI  - Effect of D-400, a herbal formulation, on blood sugar of normal and alloxan
      induced diabetic rats.
AB  - Blood sugar levels of normal rats treated with D-400 showed significant reduction
      (P < 0.05) as compared to control groups. The fall was seen at one month and
      remained so uptill 3 months. Hyperglycemic response to adrenaline was
      significantly lowered (P < 0.05) following D-400 treatment. D-400 potentiated the
      hypoglycemia following tolbutamide treatment. Blood sugar remained persistently
      low in tolbutamide plus D-400 treated group after 3 and 4 hours (P < 0.05). In
      the alloxan-induced diabetic rats, a significant lowering of blood and urinary
      sugar was noticed on day 20, 30 and 40 following treatment with D-400 (P < 0.05).
      Liver glycogen depletion was significantly inhibited in the D-400 treated group
      (P < 0.025). D-400 has significantly potentiated (P < 0.05) the hypoglycemic
      action of insulin in alloxan-induced diabetic rats.

PMID- 7649615
TI  - Phagocytic microglia during delayed neuronal loss in the facial nucleus of the
      rat: time course of the neuronofugal migration of brain macrophages.
AB  - The injection of Fluoro-Gold (FG) into the whisker pad of rats yields a stable
      fluorescent labeling of the motoneurons in the lateral facial subnucleus.
      Following resection of 8-10 mm of the facial nerve, the microglia phagocytose the
      FG-preloaded neurons and assume the label. Employing this vital labeling of
      microglia in situ we studied the fate of same after completion of phagocytic
      activity. Starting at 56 days post resection (DPR) the FG-labeled microglia
      spread out from the lateral facial subdivision and invaded the entire facial
      nucleus. The quantitative analysis of this redistribution of the fluorescent
      marker revealed a prolonged increase in the number of labeled microglia strictly
      proportional to the delayed loss of neurons. The differentiation between
      microglia and shrunken neurons was performed with the new method of
      immunoquenching: the staining of vibratome sections with anti-rat neuron-specific
      enolase (NSE) combined with an ABC-HRP kit and DAB as detector totally
      extinguished (quenched) all fluorescence from the pre-labeled facial motoneurons.
      The fluorescent microglia were additionally stained with GSA I-B4 and OX-42,
      which should completely quench all fluorescence in the section. However, a few
      small round cells, always closely opposed to neuronal perikarya, still
      fluoresced. These NSE-negative, GSA I-B4 and OX-42 negative, but fluorescent
      cells may represent a new, immunologically uncharacterized microglial cell type,
      that participates in neuronophagia.

PMID- 7649616
TI  - Binding and action of glucagon in cultured mouse astrocytes.
AB  - This study investigates glucagon binding in primary cultures of differentiated
      mouse astrocytes and the effect of glucagon on intracellular cAMP accumulation.
      Binding of 125I-glucagon (0.53 nM) to mouse astrocyte suspensions reached
      equilibrium after 10 min at 22 degrees C. Equilibrium binding corresponded to 46
      +/- 15 pmol/mg protein (n = 3) representing approximately 10,000 occupied sites
      per cell at the tracer concentration used. Dissociation occurred with a half-time
      of 2.5 min at 22 degrees C and was not accelerated in the presence of unlabelled
      glucagon (1 microM). Scatchard analysis suggested the presence of more than one
      class of binding site. The Ka for the higher affinity sites was 5.7-7.4 x 10(6) M
      1. The Ka for the lower affinity sites was 3.6-5.3 x 10(4) M-1. The results
      suggest the presence of approximately 43,000 high affinity sites per cell.
      Binding was inhibited by unlabelled glucagon with an IC50 of 50 nM but unaffected
      by insulin and somatostatin. However, no 125I-glucagon binding could be detected
      when intact monolayer cells attached to culture dishes were used. Glucagon
      stimulated cyclic-AMP accumulation in both cell suspensions and intact monolayer
      cells in a dose-dependent fashion. However high concentrations were required when
      compared to the receptor-binding studies. Marked degradation of 125I-glucagon by
      astrocytes during binding experiments was observed and this was inhibited by
      unlabelled glucagon but also by insulin and desoctapeptide insulin.

PMID- 7649617
TI  - Glial cell transplants that are subsequently rejected can be used to influence
      regeneration of glial cell environments in the CNS.
AB  - Transplantation of glial cells into demyelinating lesions in CNS offers an
      experimental approach which allows investigation of the complex interactions that
      occur between CNS glia, Schwann cells, and axons during remyelination and repair.
      Earlier studies have shown that 1) transplanted astrocytes are able to prevent
      Schwann cells from participating in CNS remyelination, but that they are only
      able to do so with the cooperation of cells of the oligodendrocyte lineage, and
      2) transplanted mouse oligodendrocytes can remyelinate rat axons provided their
      rejection is controlled by immunosuppression. On the basis of these observations,
      we have been able to prevent the Schwann cell remyelination that normally follows
      ethidium bromide demyelination in the rat spinal cord by co-transplanting
      isogeneic astrocytes with a potentially rejectable population of mouse
      oligodendrocyte lineage cells. Since male mouse cells were used it was possible
      to demonstrate their presence in immunosuppressed recipients using a mouse Y
      chromosome probe by in situ hydridisation. When myelinating mouse cells were
      rejected by removal of immunosuppression, the demyelinated axons were
      remyelinated by host oligodendrocytes rather than Schwann cells, whose entry was
      prevented by the persistence of the transplanted isogeneic astrocytes. The
      oligodendrocyte remyelination was extensive and rapid, indicating that the
      inflammation associated with cell rejection did not impede repair. If this host
      oligodendrocyte remyelination was prevented by local X-irradiation, the lesion
      consisted of demyelinated axons surrounded by processes from the transplanted
      astrocytes. By this approach, it was possible to create an environment which
      resembled the chronic plaques of multiple sclerosis. Thus, these experiments
      demonstrate that in appropriate circumstances the temporary presence of a
      population of glial cells can alter the outcome of damage to the CNS.

PMID- 7649618
TI  - Laser cytometric analysis of FIV-induced injury in astroglia.
AB  - Glia are the predominant brain cells infected by the lentiviruses human
      immunodeficiency virus (HIV) and feline immunodeficiency virus (FIV). The
      importance of astrocytes in maintenance of central nervous system homeostasis
      suggests that astrocytes are likely to play a strategic role in the progression
      of neurological disease in lentiviral-infected patients. In consideration of this
      postulate, the ability of FIV to cause injury by infection of cultured feline
      astroglia was examined via vital fluorescence assays. Intracellular Ca2+
      homeostasis, plasma membrane permeability and fluidity, and cytosolic glutathione
      (GSH) levels were evaluated. Although basal intracellular Ca2+ was not
      significantly different between groups, FIV-infected astroglia displayed both a
      significant delay in development of peak Ca2+ levels following ionophore
      application and a decrease in the amount of Ca2+ released from intracellular
      stores. Plasma membrane lipid mobility was increased in FIV-infected cells within
      24 h of infection. Glutathione levels were affected in a dose dependent fashion.
      With a standard viral inoculum there was a decrease in GSH which became
      significant after 8 days postinfection. With a high inoculum dose there was rapid
      loss of cell viability with an increase in GSH in surviving cells. We have
      identified several cellular processes altered in FIV-infected astroglia and our
      findings suggest that FIV-infection of feline astroglia affects cellular
      membranes, both structurally and functionally.

PMID- 7649619
TI  - Surgical treatment of both-column fractures by staged combined ilioinguinal and
      Kocher-Langenbeck approaches.
AB  - Between 1981 and 1989, 18 patients affected by both-column acetabular fractures
      were operated on by staged combined ilioinguinal and Kocher-Langenbeck
      approaches. Postoperative reduction quality and long-term radiographic results
      were evaluated according to the Matta radiological systems. The Harris hip
      scoring system was used for the functional results. Average follow-up was 53.2
      months, ranging from 24 to 132 months. Reduction was anatomical in five cases
      (27.8 per cent), satisfactory in 11 (67.1 per cent), and non-anatomical in two
      cases (11.1 per cent). Radiographic long-term results were excellent in nine
      cases (50 per cent), good in five (27.8 per cent), fair in two (11.1 per cent)
      and poor in two (11.1 per cent). The Harris score was more than 90 in eight
      patients (44.4 per cent), between 80 and 90 in seven (38.8 per cent), between 80
      and 70 in one (5.5 per cent), and less than 70 in two (11.1 per cent).

PMID- 7649620
TI  - Traumatic prepatellar neuralgia.
AB  - Fourteen patients with painful knees caused by a direct blow to the front of the
      knee have been studied. The exact diagnosis was often delayed. Apart from pain,
      all patients had one common feature which they may not have been aware of,
      namely, marked tenderness localized towards the middle of the outer border of the
      patella. Surgical treatment in 11 patients, by excision of the subcutaneous
      tissue in the tender area and the prepatellar bursa, cured all cases. Histology
      of the excised specimens confirms the existence of a definite clinico
      pathological entity.

PMID- 7649621
TI  - Carpal malalignment following intra-articular fractures of the distal radius in a
      working population.
AB  - In a review of 52 consecutive intra-articular fractures of the wrist (mean age 41
      years), 18 developed one of five carpal malalignment patterns. Seven patients
      developed a volar intercalated collapse pattern. Although showing some loss of
      motion and/or grip strength, this group remains relatively pain free on follow
      up. Patients who developed dorsal translation (six cases) or a dorsal
      intercalated collapse pattern (one case) were the most symptomatic, with loss of
      grip strength, decreased range of motion and pain being prevalent.

PMID- 7649622
TI  - Death after proximal femoral fracture--an autopsy study.
AB  - We reviewed 22,486 consecutive autopsy reports in a single District General
      Hospital, from 1953 to 1992. Five hundred and eighty-one patients with fractures
      of the proximal femur (hip fracture) were identified. Causes of death were
      correlated with timing of surgery and change of clinical practice. Thromboembolic
      and haemorrhagic potential were analysed. The principal causes of death after hip
      fracture were bronchopneumonia, cardiac failure, myocardial infarction and
      pulmonary embolism. Surgical intervention, within 24 h of injury significantly
      reduced death from bronchopneumonia and pulmonary embolism. Early mobilization
      reduced death from bronchopneumonia. Pulmonary embolism may be reduced by
      prophylactic anticoagulation, but 17 per cent of patients are at risk of
      haemorrhage, and mechanical methods seem safer in this population.

PMID- 7649623
TI  - The dynamic condylar screw in the management of subtrochanteric fractures of the
      femur.
AB  - We reviewed 43 patients with subtrochanteric fractures treated with the AO
      dynamic condylar screw (DCS) to determine the medical and technical complication
      rate. Seven patients died before union and nine sustained major medical
      complications. Thirty fractures united without event. There were six technical
      failures, three related to failure of the medial buttress. The DCS can be used
      successfully in most subtrochanteric fractures, although there is a considerable
      complication rate, which reflects the general condition of the patient and the
      biomechanics of the proximal femur.

PMID- 7649624
TI  - External fixation as a primary and definitive treatment of open limb fractures.
AB  - This paper analyses the medical records of 5024 injured persons treated and
      operated on at the Surgical Clinic of the Clinical Hospital in Osijek, during the
      war against Croatia (1991 and 1992). There were 1653 (33.0 per cent) admitted,
      while the rest were treated as out-patients. Of the admitted patients 82.7 per
      cent (1372) had limb injuries. In 760 (15.0 per cent) of the wounded, 1320 limb
      fractures caused by explosives were diagnosed, out of which 856 were of the lower
      and 464 of the upper limbs. One hundred and ninety-two (3.9 per cent) were
      treated by external fixation. External fixators were applied to 147 lower and 68
      upper open long bones, respectively. Adequate reconstructive operations were
      performed on 106 (2.1 per cent) patients with associated injuries to important
      blood vessels. The stabilization of the open and unstable external fractures was
      achieved by external fixation, mostly at one level, regardless of the wound size.
      The importance of good wound cleaning has been particularly stressed as well as
      bone fragment reposition. Special attention has been given to the preoperative
      and intra-operative assessment of the limbs. In 20 patients (9.3 per cent)
      treated with external fixation, osteitis occurred. Twenty-one more patients (9.7
      per cent), because of bad fracture healing after external fixation, were
      submitted to secondary internal bone fixation combined with bone grafts. Out of
      these, nine (42.8 per cent) developed osteitis as a consequence of the additional
      treatment.

PMID- 7649625
TI  - Penetrating injuries of the brachial artery.
AB  - This is a retrospective study of 72 patients with non-iatrogenic penetrating
      injuries of the brachial artery treated between 1991 and 1993. The mechanism of
      injury was stabbing in 39 per cent, a bullet in 51 per cent, pellets in 4 per
      cent and a dog bite in 6 per cent. We believe that angiography is rarely
      indicated, as in all our patients the diagnosis was made on clinical grounds. The
      proximity of the injury to neurovascular bundles was a poor predictor of arterial
      injury. One month after discharge 95 per cent of the patients had palpable distal
      pulses. Long-term morbidity is mainly attributed to associated nerve injuries.

PMID- 7649626
TI  - A method to measure the value of formal training in trauma management: comparison
      between ATLS and induction courses.
AB  - The change in knowledge resulting from formal training in trauma management on
      two different courses was examined. Seventy-four doctors and a control group were
      included in this prospective study over a 2-year period. They represented
      participants on two Advanced Trauma Life Support (ATLS) courses and four
      induction courses for junior doctors in Accident and Emergency (A&E) departments.
      The results indicate substantial benefits from both types of training. The ATLS
      course participants achieved better scores. Steps in constructing a simple test
      for the evaluation of courses are described. Standardization of approach is
      recommended. Assessment and audit of training in trauma management is feasible
      with limited resources. It may eventually be possible to measure individual
      clinician's proficiency against a standard scale.

PMID- 7649627
TI  - Immediate intramedullary nailing of femoral shaft fractures due to gunshots.
AB  - With increasing violence in our society, the number of gunshot fractures is
      likely to increase. Fourteen femoral fractures caused by gunshot injuries were
      treated with statically locked intramedullary nailing within 8 h of injury. Three
      patients had concomitant femoral arterial injuries. At follow-up (average 22
      months) the results were assessed using a standardized grading system. Thirteen
      fractures had progressed to stable bony union and there were no deep infections.
      Nine fractures had an excellent outcome and four a good outcome. One fracture was
      graded as a poor outcome because of a non-union which was treated with an
      exchange nailing procedure and progressed to bony union. Our experience of
      immediate intramedullary nailing of gunshot femoral fractures has yielded results
      which approximate to those observed in treating closed femoral fractures. We
      would therefore recommend this as the treatment of choice in fractures of the
      femoral shaft caused by gunshots.

PMID- 7649628
TI  - Severe upper limb injuries in four passengers of a 'People Carrier'; the
      contribution of design faults.
AB  - Four passengers of a 'People Carrier' in a single vehicle motor accident
      sustained severe left upper limb trauma, when the vehicle rolled onto the near
      side. These injuries were directly attributable to the large glass interface
      between patient and road. The glass windows shattered on contact, providing no
      protection and in effect created a secondary injury mechanism. We advocate both
      the use of laminated side windows and mandatory testing of 'roll-over'
      characteristics for these 'People Carriers' to reduce the incidence of such
      injuries.

PMID- 7649629
TI  - Being overweight and multiple fractures are indications for operative treatment
      of humeral shaft fractures.
AB  - Excellent clinical results can be obtained with non-operative treatment of
      humeral shaft fractures. In certain patients, operative stabilization is the
      treatment of choice. This study was initiated to determine the results of non
      operative treatment in relation to multiple fractures and being overweight. From
      1985 to 1992 we treated 35 humeral shaft fractures in 34 patients by non
      operative methods. The median age was 51 (18-84) years. There were 12 women and
      22 men. Nine were in overweight patients and 11 were in patients with multiple
      fractures. Fractures in overweight patients were followed for 158 (60-597) days
      and the Neer score was 61 (50-72) points. Patients with multiple fractures were
      followed for 178 (52-970) days and the Neer score was 72 (38-96) points. Single
      fractures in non-overweight patients were followed for 70 (35-412) days and the
      Neer score was 94 (65-100) points. These results show that humeral shaft
      fractures in certain patients may best be treated by operative stabilization.

PMID- 7649630
TI  - How safe the 'banana' boat?

PMID- 7649632
TI  - Head injury secondary to ruptured abdominal aortic aneurysm: an unusual
      presentation.

PMID- 7649631
TI  - Fractured lateral epicondyle associated with lateral elbow instability.

PMID- 7649633
TI  - Head in-situ hip hemiarthroplasty.

PMID- 7649634
TI  - Intra-articular dislocation of patella.

PMID- 7649635
TI  - Isolated complete rupture of biceps femoris tendon.

PMID- 7649636
TI  - Bowing injury of forearm in an adult.

PMID- 7649637
TI  - A case of transorbital intracranial damage underlying a seemingly innocuous
      injury.

PMID- 7649638
TI  - Delayed diagnosis of an odontoid process fracture in an infant.

PMID- 7649639
TI  - Early awareness of post-traumatic coagulopathy.

PMID- 7649640
TI  - Injuries from forklift trucks.

PMID- 7649641
TI  - Extraction of broken intramedullary nails--an improvement in technique.

PMID- 7649642
TI  - The results of surgical management of displaced tibial plateau fractures in the
      elderly.
AB  - We retrospectively reviewed 32 elderly patients (mean age 71.7 years, range 66-83
      years) with displaced tibial plateau fractures after a mean of 3.7 years (range 1
      7 years) after operative treatment. Schatzker type 2 fracture was the commonest
      pattern of fracture (60.3 per cent). According to the modified Rasmussen clinical
      and radiographic criteria, there were nine excellent, 14 good, five fair and four
      poor results clinically, and 11 excellent, 12 good, six fair and three poor
      results radiographically. There was no significant correlation between the final
      radiographic appearance and clinical outcome. Fourteen patients mobilized
      postoperatively on a continuous passive motion machine followed by a cast brace
      had a better result than those mobilized in a cast brace alone, but the
      difference was not statistically significant (P = 0.29). Postoperative
      complications included deep vein thrombosis in two patients.

PMID- 7649643
TI  - Treatment of closed tibial shaft fractures with unilateral external fixation.
AB  - Sixty-eight closed tibial shaft fractures were treated with an anterior
      unilateral external fixator over a 5 year period (1986-1991). Pin tract drainage
      and/or infection was seen in 71/380 pins. The total number of secondary
      operations, excluding planned pin extraction, during fracture healing was 61
      (including 22 due to pin tract problems and 25 secondary corrections of
      alignment). Delayed union was seen in 14 fractures and non-union in three.
      Healing disturbances were more frequent following high-energy trauma. Bone
      grafting was done in 11 fractures. Eventually, all fractures healed within an
      average of 22 weeks. There were three refractures. At follow-up, on average 3
      years after injury, functional results were excellent in 41 per cent, good in 46
      and acceptable in 13 per cent. Due to the high number of unplanned secondary
      operations and prolonged healing times we do not consider the use of unilateral
      external fixation to be an adequate method for the treatment of closed tibial
      shaft fractures. The poor results are probably due to weight-bearing being too
      high in these patients relative to the mechanical stability provided by the
      external fixator system.

PMID- 7649644
TI  - Evaluation of subxiphoid pericardial window used in the detection of occult
      cardiac injury.
AB  - We critically evaluated several diagnostic modalities (clinical criteria,
      subxiphoid pericardial window (SPW) and laparoscopy) used in the detection of
      occult cardiac injury in haemodynamically stable patients at high risk of cardiac
      injury. Over 5 years, 122 patients were admitted to a Level I trauma centre with
      such an injury. They sustained 69 stab wounds, and 53 gunshot wounds. Sites of
      penetration were: precordial (81), right chest (25), lateral chest (13),
      thoracoabdominal (40) and abdominal (19). Vital signs in the emergency room were
      (mean +/- SD): systolic BP, 111 +/- 23.2 mmHg; HR, 106 +/- 18.7; GCS, 13.6 +/-
      1.3; and CVP, 17 +/- 7.8 cmH2O. SPW was performed in all patients and was
      positive for haemopericardium in 26 patients, 24 (92 per cent) of whom had a
      cardiac injury at operation. Two patients had pericardial lacerations without
      cardiac injury. In addition, 14 patients with lower precordial and
      thoracoabdominal wounds underwent laparoscopy. At laparoscopy, the pericardium
      was evaluated by transdiaphragmatic inspection in 10 patients. The presence (two)
      or absence (eight) of blood within the pericardium was accurately predicted and
      verified by SPW. Univariate and multiple logistic regression analysis of clinical
      data failed to reveal any significant predictor of cardiac injury. SPW remains
      the standard means of diagnosing occult cardiac injury in high-risk patients.
      Since the incidence of occult cardiac injury in haemodynamically stable patients
      is 20 per cent, SPW should be used liberally. Laparoscopy may have a role in
      evaluating the pericardium in the subgroup of patients with lower chest wounds,
      and it facilitates inspection of intra-abdominal viscera and diaphragm at the
      same time.

PMID- 7649645
TI  - The relationship between alcohol intoxication, injury severity and Glasgow Coma
      Score in assault patients.
AB  - To assess the effect of alcohol intoxication on injury severity and head injury
      assessment, blood alcohol concentrations (BAC) were related to the severity of
      injuries (Injury Severity Score and Assault Trauma Score) and Glasgow Coma Scores
      (GCS) in 242 consecutive victims of weekend, night-time assault, none of whom had
      head injuries. No correlation was found between degree of intoxication and
      severity of injury. There was a highly significant correlation between BAC and
      GCS. However, high BACs (greater than 240 mg/100 ml) were associated with only a
      2-3 point reduction in GCS. The median BAC in patients with a normal GCS was 115
      mg/100 ml. Neurological assessments need to take account of the highly variable,
      depressive effects of alcohol.

PMID- 7649646
TI  - Low level laser therapy: a prospective double blind trial of its use in an
      orthopaedic population.
AB  - We have conducted a prospective, double blind trial of low level laser therapy
      (LLLT) in musculoskeletal injuries to assess its efficacy. We assigned patients
      with a variety of painful skeletal soft tissue conditions to one of two treatment
      groups, treatment from a functional machine, placebo treatment from an inactive
      machine. Both machines were identical and both appeared functional. The operative
      status of each machine was unknown to both the therapist and the patient. The
      results suggest that LLLT has no significant therapeutic effect and acts
      primarily as a placebo.

PMID- 7649647
TI  - Femoral neck fracture: a complication of femoral nailing.
AB  - A fracture of the shaft of the femur in adults is common after road traffic
      accidents. Until recently it was not known that a fracture of the femoral neck
      can occur while fixing the femoral shaft fracture with an intramedullary nail. We
      report three patients in whom femoral neck fractures occurred during femoral
      nailing. Fractures of the femoral neck were detected by routine postoperative
      radiographs of the hip joint. All the three patients were treated non-operatively
      and the fractures healed without complication. The cause of the femoral neck
      fracture seems to be forceful use of an awl in the wrong direction or multiple
      entry points in the trochanteric region which weaken the femoral neck; subsequent
      hammering of the nail completes the fracture.

PMID- 7649648
TI  - Open fractures of the femoral shaft, treated with osteosynthesis or temporary
      external fixation.
AB  - Controversy surrounds the treatment of open femoral shaft fractures, especially
      in the multiply injured. We report on 54 patients with 57 open femoral shaft
      fractures. They were treated according to our policy which deals with the
      severity of the soft-tissue damage. Low-grade open femoral fractures were
      primarily treated with internal fixation. A temporary external fixator was used
      for high-grade open fractures and in multiply injured patients where primary
      intramedullary nailing was contra-indicated. The external fixator was converted
      into an intramedullary nail as soon as the local soft-tissue disorders and the
      general condition of the patient permitted. There were no cases of deep
      infection. There was one case of malunion. Functional outcome was good to
      excellent in all cases. The aim of this paper is to show that low-grade open
      femoral fractures can be safely treated with primary intramedullary nailing and
      that temporary external fixation of severe open fractures followed by conversion
      into an intramedullary nail can be done without deep infection.

PMID- 7649649
TI  - The pelvic fracture in childhood: a report supporting nonoperative management.
AB  - A 12 year retrospective review provides a group of 68 children with pelvic
      fractures. The distribution and type of fractures are similar to those of adults.
      The most common aetiology is an automobile-pedestrian accident. The average age
      is 8 years; male patients are nearly twice as common. Over 73 per cent are stable
      injuries. The fractures rarely occurred as isolated injuries. Morbidity is
      related to associated injury, both orthopaedic and non-orthopaedic. One-third of
      patients had an associated head injury. Over 10 per cent of patients had a
      urethral injury, an incidence higher than in published series. This review,
      coupled with a literature review, supports a nonoperative approach in orthopaedic
      management of the child.

PMID- 7649650
TI  - Are hard-copy prints from peroperative fluoroscopy images useful as
      documentation?
AB  - We have examined the applicability of peroperative image documentation, in
      promoting early mobilization after osteosynthesis and saving the standard X-ray
      examination. One hundred and twenty-three patients with proximal femoral
      fractures were included in the investigation. Hard-copy reprints were recorded
      from peroperative fluoroscopy images by Fuji Film Thermal Imaging System FTI 200.
      These reprints were compared with the standard X-rays to assess the quality of
      the osteosynthesis and possible restriction in mobilization. The specificity of
      finding an unstable osteosynthesis was 0.40, whereas the sensitivity of finding a
      stable osteosynthesis was 0.96. In all, four unstable osteosyntheses were
      overlooked on the hard copy reprints. The specificity of finding patients in need
      of restricted mobilization was 0.44 and the sensitivity of finding patients
      allowed free mobilization was 0.93. Eight patients needing restricted
      mobilization were overlooked on the reprints. Hard-copy images do not safely
      reveal unstable osteosynthesis and cannot replace the standard X-rays taken
      postoperatively.

PMID- 7649651
TI  - Skull fractures in children: altered conscious level is the main indication for
      urgent CT scanning.
AB  - It has been suggested that all children with skull fractures require urgent CT
      scanning to exclude intracranial injury. Adhering to such a policy could both tax
      limited scanning facilities and result in unnecessary exposure to radiation. The
      aim of this study is to assess the level of consciousness in determining the need
      for urgent CT scanning, and the possible role of the mechanism of injury as a
      secondary risk factor. We identified 140 children admitted during a 7-year period
      with a skull fracture after falling outside the home. Thirteen children had a
      diminished level of consciousness. Scans were performed in nine, and seven of the
      scans revealed significant intracranial injuries. By comparison, all 127 children
      with a normal level of consciousness recovered fully. Scanning was performed in
      only eight of them; seven scans were normal and one revealed a small subarachnoid
      heamorrhage which did not require active treatment. In addition, all 13 children
      with a diminished level of consciousness had sustained their injuries by falling
      from greater than their own standing height. By comparison, none of the children
      who had sustained their skull fractures by tripping up had a diminished level of
      consciousness or a significant intracranial injury. We conclude that all children
      with a diminished level of consciousness need to undergo an urgent CT scan.
      Children with skull fractures and a normal conscious level may be managed
      initially by neuroobservations and the clinician may be further reassured if the
      child's injury resulted from tripping up.

PMID- 7649653
TI  - Blunt abdominal injury associated with colonic rupture into abdominal muscles.

PMID- 7649652
TI  - The perceived relationship between back symptoms and preceding injury.
AB  - A questionnaire was used to gather information regarding the prevalence of minor
      back symptoms related to performing everyday tasks, including sitting, lifting,
      etc. in a population of hospital employees. We studied 175 subjects, of whom 111
      had not suffered a back injury. Of this group, 68 (61.3 per cent) had suffered
      back discomfort during or after performing everyday tasks. Sixty-four reported a
      previous injury to their back, and of these 55 (85.9 per cent) described back
      discomfort during or after performing everyday tasks. Of the symptomatic cases,
      46 (83.3 per cent) maintained that they had no back symptoms prior to their
      injury, and attributed all of their back symptoms to the injury. The chi 2 test
      was used to test the null hypothesis that the group attributing their symptoms to
      injury was derived from the same population as the group who had not suffered any
      definite injury, and yet had back symptoms. This hypothesis was rejected (P <
      0.001), indicating that there was a significant difference between these two
      groups. We conclude that individuals who sustain a back injury sometimes do not
      recall that they suffered symptoms prior to their injury. This may be of medico
      legal importance in cases where compensation is being sought.

PMID- 7649654
TI  - Life-threatening retropharyngeal haematoma.

PMID- 7649655
TI  - Delayed ulnar tunnel syndrome following a minor closed wrist injury.

PMID- 7649656
TI  - Ischaemic anterior interosseus nerve injuries following supracondylar fractures
      of the humerus in children.

PMID- 7649657
TI  - Acute cervical epidural haematoma after soft-tissue cervical spine injury.

PMID- 7649658
TI  - Acute traumatic patellar dislocation: the importance of skyline views.

PMID- 7649659
TI  - Traumatic carotid dissection associated with cervical anomalies.

PMID- 7649660
TI  - Avascular necrosis of the femoral head following pertrochanteric fracture.

PMID- 7649661
TI  - Isolated bilateral first rib fracture associated with aortic valve tear.

PMID- 7649662
TI  - Meningitis occurring 39 years after head injury, secondary to rupture of a
      mucocele.

PMID- 7649663
TI  - Accidental third-degree burn caused by bipolar electrocoagulation.

PMID- 7649664
TI  - Intramedullary nailing technique and its effect on union rates of tibial shaft
      fractures.

PMID- 7649665
TI  - Salutary effect of Terminalia Arjuna in patients with severe refractory heart
      failure.
AB  - Twelve patients with refractory chronic congestive heart failure (Class IV NYHA),
      related to idiopathic dilated cardiomyopathy (10 patients); previous myocardial
      infarction (one patient) and peripartum cardiomyopathy (one patient), received
      Terminalia Arjuna, an Indian medicinal plant, as bark extract (500 mg 8-hourly)
      or matching placebo for 2 weeks each, separated by 2 weeks washout period, in a
      double blind cross over design as an adjuvent to maximally tolerable conventional
      therapy (Phase I). The clinical, laboratory and echocardiographic evaluation was
      carried out at baseline and at the end of Terminalia Arjuna and placebo therapy
      and results were compared. Terminalia Arjuna, compared to placebo, was associated
      with improvement in symptoms and signs of heart failure, improvement in NYHA
      Class (Class III vs. Class IV), decrease in echo-left ventricular enddiastolic
      (125.28 +/- 27.91 vs. 134.56 +/- 29.71 ml/m2; P < 0.005) and endsystolic volume
      (81.06 +/- 24.60 vs. 94.10 +/- 26.42 ml/m2; P < 0.005) indices, increase in left
      ventricular stroke volume index (44.21 +/- 11.92 vs. 40.45 +/- 11.56 ml/m2; P <
      0.05) and increase in left ventricular ejection fractions (35.33 +/- 7.85 vs.
      30.24 +/- 7.13%; P < 0.005). On long term evaluation in an open design (Phase
      II), wherein Phase I participants continued Terminalia Arjuna in fixed dosage
      (500 mg 8-hourly) in addition to flexible diuretic, vasodilator and digitalis
      dosage for 20-28 months (mean 24 months) on outpatient basis, patients showed
      continued improvement in symptoms, signs, effort tolerance and NYHA Class, with
      improvement in quality of life.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7649666
TI  - Ductus-dependent aortic coarctation with a left-to-right shunt through the
      ductus: report of one case.
AB  - A 20 days old female baby presenting with dyspnea was found to have coarctation
      of the aorta and patent ductus arteriosus by echocardiography. The Doppler
      spectral display disclosed mainly a left-to-right shunt through the ductus.
      Therefore, the prostaglandin El infusion was discontinued. She developed acute
      left heart failure, and the echocardiograms at that time showed a markedly
      narrowed juxtaductal aortic coarctation with a closed ductus. After resumption of
      prostaglandin El, with an attenuated juxtaductal aortic coarctation, the left
      ventricular contractility and the systemic perfusion improved. Therefore, we
      conclude that the central role of a patent ductus in such a patient is to avoid
      the ductal constriction which will worsen the aortic coarctation.

PMID- 7649667
TI  - Transient myocardial ischemia in patients with chronic angina: relation to heart
      rate changes and variability in exercise threshold. BAY r 1999 in Chronic Angina
      Study Group.
AB  - This study was undertaken to assess the relation of ambulatory myocardial
      ischemia to heart rate changes and variability in exercise threshold in patients
      with chronic angina. The study involved 118 patients with chronic angina and
      proven coronary artery disease who had a 'positive' exercise test result. All
      patients underwent a first exercise test followed by a 48-h period of ambulatory
      electrocardiographic monitoring. A second exercise test was performed 4 days
      later. A total of 101 ischemic episodes were recorded in 35 patients. The heart
      rate at the appearance of 1-mm ST segment depression during ambulatory
      electrocardiographic monitoring was > or = 20 beats/min lower than that during
      exercise testing in 58 ischemic episodes (57%, Group A), 10-19 beats/min lower in
      26 (26%, Group B), and < or = 9 beats/min lower or higher in 17 (17%, Group C).
      Thirty-five percent of the Group A ischemic episodes, 69% of Group B, and 71% of
      Group C were preceded by an increase in heart rate of > or = 10 beats/min. Thirty
      patients showed a variable exercise threshold. The prevalence of Group A and B
      ischemic episodes was not significantly different in patients with fixed or
      variable exercise threshold, whereas that of Group C episodes was 22% in the
      former and 0% in the latter (P = 0.036). These results suggest that increased
      coronary tone may be one of the mechanisms contributing to modulate the
      occurrence of transient myocardial ischemia in most patients with chronic angina
      and transient myocardial ischemia at ambulatory electrocardiographic monitoring.
      This occurs regardless of whether the patients have a variable or fixed exercise
      threshold.

PMID- 7649668
TI  - Chronotropic incompetence in chronic heart failure.
AB  - BACKGROUND: The exercise limitation of patients with chronic heart failure may be
      due in part to an inability to increase heart rate as normal, a limitation
      sometimes referred to as chronotropic incompetence. This may be due to down
      regulation of beta receptors. METHODS: Fifty-seven patients with chronic heart
      failure and 14 age-matched controls underwent symptom limited treadmill exercise
      tests with metabolic gas exchange measurements. Heart rate and blood pressure
      responses were also recorded. RESULTS: Peak oxygen consumption was reduced in the
      heart failure patients (19.6 (S.D. +/- 7.6) vs. 35.0 (+/- 9.9); P < 0.001). Heart
      rate at peak exercise (r = 0.47, P < 0.001), and change in heart rate from rest
      to peak exercise (r = 0.59; P < 0.001) and rate pressure product at peak exercise
      (r = 0.56, P < 0.001) all correlated with peak oxygen consumption. The percentage
      of predicted maximal heart rate at peak exercise correlated poorly with peak
      oxygen consumption (r = 0.29; P > 0.05). Peak systolic and diastolic blood
      pressures did not correlate with peak oxygen consumption. Sixteen patients had
      chronotropic incompetence. There was no significant difference between this group
      and those without chronotropic incompetence in the intensity of exercise
      performed, underlying diagnosis, drug therapy or prevalence of atrial
      fibrillation. There was a trend towards shorter exercise times in the incompetent
      group (430 (+/- 251) vs. 545 (+/- 216) s; P = 0.08) compared to the other
      patients. CONCLUSIONS: Chronotropic incompetence was seen in < 30% of patients
      with chronic heart failure. However, there are few differences between the group
      with chronotropic incompetence and the group without. Chronotropic incompetence
      is thus unlikely to be a major factor limiting exercise capacity in unselected
      patients with chronic heart failure and is likely to be the major factor limiting
      exercise in a much smaller proportion of patients.

PMID- 7649669
TI  - Adrenal tumour, congestive heart failure and hemiparesis in an 18-year-old male.
      A clinical-pathological conference.
AB  - A case of a young male presenting with mild hypertension, congestive cardiac
      failure, stroke in the distribution of the left middle cerebral artery and a
      right suprarenal mass is discussed. Diagnostic and therapeutic strategies are
      presented.

PMID- 7649670
TI  - Physical work capacity with rate responsive ventricular pacing (VVIR) versus dual
      chamber pacing (DDD) in patients with normal and diminished left ventricular
      function.
AB  - To determine the benefit of atrial contribution on work capacity in relation to
      left ventricular ejection fraction, we studied 17 patients (68 +/- 13 years) with
      dual chamber pacemakers (DDD) implanted for high degree atrioventricular (AV)
      block. In random order they were assigned to rate responsive ventricular (VVIR)
      and to atrial triggered ventricular (VDD) stimulation. Maximum oxygen uptake (max
      VO2), that correlates best with work capacity, was measured by spiroergometry at
      a respiratory quotient of 1.1 during treadmill exercise test. Left ventricular
      ejection fraction at rest was determined by radionuclide ventriculography during
      VDD-stimulation and an AV delay of 150 ms. There were no differences between
      these two pacing modes relating heart rate, blood pressure, minute ventilation,
      exercise duration and maximal work load. In eight patients with an ejection
      fraction > 50% (60 +/- 10%), but not in nine patients with an ejection fraction <
      50% (41 +/- 10%), maximum oxygen uptake was significantly higher (P < 0.01)
      during atrial triggered ventricular pacing (1440 +/- 533 ml/min) compared with
      rate responsive ventricular pacing (1328 +/- 536 ml/min). Thus, rate responsive
      single chamber pacemakers largely enable the same work capacity as dual chamber
      pacemakers in patients with high degree AV block. Patients with normal left
      ventricular function may profit most from preserved AV synchrony as shown by the
      higher maximum oxygen uptake on exercise.

PMID- 7649671
TI  - Dysrhythmic profile of human immunodeficiency virus infected patients.
AB  - We prospectively studied, with 24-h Holter monitoring, 21 consecutive human
      immunodeficiency virus (HIV) infected patients, at all stages of the infection,
      in order to assess their dysrhythmic profile. Three (14.3%) patients presented
      one isolated run of supraventricular tachycardia, with < 10 beats, that was
      considered clinically irrelevant. No patient presented other clinically relevant
      supraventricular or ventricular tachy or bradydysrhythmias. One (4.8%) patient
      presented intermittent Mobitz type I second-degree AV block, two (9.5%) patients
      paroxistic 2:1 AV block and one (4.8%) patient presented a bifascicular block on
      the 12-lead ECG that persisted during the ambulatory recording. This study
      suggests that clinically relevant cardiac tachydysrhythmias are rare in our
      population of HIV infected patients. On the other hand we found an unexpectedly
      high incidence of cardiac impulse conduction disturbances.

PMID- 7649672
TI  - Atrial septal aneurysm and cardiac arrhythmias.
AB  - Atrial septal aneurysm has been associated with thromboembolic events,
      interatrial shunting, mitral valve prolapse, and systolic click. An association
      between atrial septal aneurysm and cardiac arrhythmias has been also described.
      Twenty patients with atrial septal aneurysm and 19 control subjects performed 24
      h Holter monitoring. Frequent (> 10/h) atrial premature beats were observed in
      seven patients vs. none of the controls (P = 0.008). The mean number of episodes
      of supraventricular tachycardia and the prevalence of ventricular tachycardia
      were also higher in the atrial septal aneurysm group (P = 0.044 and P = 0.046,
      respectively). Left atrial enlargement, mitral valve prolapse and left
      ventricular hypertrophy were more frequent than in the normal subjects. In
      conclusion, atrial and ventricular 'complex' arrhythmias occurred more frequently
      in patients with atrial septal aneurysm than in normal subjects. Further studies
      in patients with atrial septal aneurysm without other associated
      echocardiographic abnormalities need to be done to ascertain a potential
      arrhythmogenicity of this condition.

PMID- 7649673
TI  - Are Asian coronary arteries smaller than Caucasian? A study on angiographic
      coronary artery size estimation during life.
AB  - Asian immigrants to the UK have a higher mortality from coronary artery disease
      (CAD) than native Caucasians. There is a clinical impression that Asians have
      smaller coronary arteries than Caucasians. In the present study, consecutive
      series of 72 male Caucasian and 70 male Asian patients undergoing diagnostic
      coronary angiography were recruited. Measurements of proximal disease-free
      segments of the three major coronary arteries were made using the catheter tip as
      the calibrating object. Electronic callipers were used for all measurements.
      Total coronary artery diameter was derived by adding the diameters of right, left
      anterior descending and circumflex arteries. Asians had significantly smaller
      total vessel diameter compared to Caucasians. They also had smaller body surface
      areas. This observation has important therapeutic implications regarding coronary
      intervention in this ethnic group already suffering excess mortality from CAD.

PMID- 7649674
TI  - Severe myocarditis and esophagitis during reversible long standing Chagas'
      disease recrudescence in immunocompromised host.
AB  - An unusual form of reagudization of Chagas' disease, from its indeterminate
      phase, was documented in an immunocompromised patient. Long-standing progressive
      visceral aggression due to extensive intracellular proliferation of T. cruzi
      manifested by severe isolated right ventricular failure and esophageal
      ulcerations. Antiparasite chemotherapy was effective in the control of the
      disease.

PMID- 7649675
TI  - Sudden death in mitral valve prolapse with Holter monitoring-documented
      ventricular fibrillation: evidence of coexisting arrhythmogenic right ventricular
      cardiomyopathy.
AB  - We report the case of a 42-year-old female, affected by mitral valve prolapse and
      ventricular arrhythmias, who died suddenly from ventricular fibrillation recorded
      during Holter monitoring. The lethal arrhythmia initiated with late diastolic
      couplets followed by a ventricular tachycardia that eventually degenerated into
      ventricular fibrillation. The patient had experienced four orthostatic and stress
      related syncopal episodes, associated with nausea and diaphoresis, and a positive
      tilt test. Holter monitoring documented ventricular arrhythmias, consisting of
      both isolated monomorphic and sporadic repetitive beats. Her standard ECG and
      exercise test were normal, but signal-averaged study findings were significantly
      positive. QT prolongation in the absence of arrhythmias was observed during the
      Valsalva manoeuvre and isoproterenol infusion. 2D echo showed a remarkable mitral
      valve prolapse without regurgitation and localized structural abnormalities of
      the right ventricle. Postmortem study confirmed mitral valve prolapse, and also
      disclosed pulmonary infundibulum dilatation, massive adipose infiltration of the
      right ventricular free wall, patchy fibrosis and scattered myocardial
      inflammatory infiltrates in the left ventricle; these features are all consistent
      with arrhythmogenic right ventricular cardiomyopathy.

PMID- 7649676
TI  - Thrombolytic therapy in acute pancreatitis presenting as acute myocardial
      infarction.

PMID- 7649677
TI  - Myocardial ischemia induced by topical use of 5-fluorouracil.
AB  - An 85-year-old woman, with known stable angina pectoris, was prescribed 5
      fluorouracil cream to treat a small basal cell carcinoma on the forehead. Half an
      hour after application the patient developed her typical ischemic pain which
      persisted for 2 hours. Rechallenge, during hospitalization, resulted in
      recurrence of symptoms that were effectively controlled with sublingual
      isosorbide dinitrate. Prophylactic therapy with nitroglycerin patch enabled
      further use of the 5-fluorouracil cream for the next month.

PMID- 7649678
TI  - Coronary angioplasty of anomalous right coronary artery originating from the left
      sinus of Valsalva.
AB  - Coronary angioplasty of an anomalous coronary artery can be technically
      challenging because of difficulty in cannulating the aberrant vessel and in
      obtaining a stable guiding catheter position. Only three cases with the right
      coronary artery originating from the left sinus of Valsalva were previously
      reported. We present a new case in which a successful angioplasty was obtained
      using a Williams LR guiding catheter.

PMID- 7649679
TI  - The effect of chondroitinase ABC on rabbit intervertebral disc. Radiological,
      histological and electron microscopic findings.
AB  - Seventy-eight rabbit lumbar discs were evaluated by radiographs and histology
      after the injection of chondroitinase ABC (40 U/ml for each disc) and compared
      with injection with phosphate buffer, and also with a control group who were not
      injected. There was considerable narrowing of the disc space after chondroitinase
      ABC injection. Safranin-0 depletion was present in the anterior part of the
      annulus fibrosus near to the nucleus pulposus in all the treated discs,
      indicating loss of proteoglycan. Electron microscopy showed collapse of the
      chondrocytes and notochordal cells. These findings suggest that chondroitinase
      ABC may be another chemonucleolytic agent which decreases disc volume and
      consequently decompresses the spinal cord or nerve roots; its effects were
      confined to the tissues within the intervertebral disc.

PMID- 7649680
TI  - Neural arch tuberculosis: a morbid disease. Radiographic and computed tomographic
      findings.
AB  - We have reviewed the clinical features, together with the radiographs and
      computerised tomography, in 9 patients with tuberculosis of the vertebral body
      and neural arch. All presented with paraparesis or paraplegia. The morbidity
      associated with this disease is so serious that it is essential to have an
      accurate means of evaluating the lesion as early as possible. Routine radiographs
      can only indicate the level of the disease and the loss of disc space, but cannot
      define the full extent of the lesion. Computed tomography shows details of the
      tuberculous involvement of the neural arch, as well as the vertebral body and
      spinal canal; the site and extent of the soft tissue lesions can also be seen.
      This is essential for evaluation of the neural arch involvement which will enable
      the clinician to select the appropriate treatment, and so prevent neurological
      complications.

PMID- 7649681
TI  - Flexibility and alignment of the cervical spine after laminoplasty for
      spondylotic myelopathy. A radiographic study.
AB  - The long term effects of laminoplasty on cervical movement and alignment were
      investigated by radiography and CT scans in a study of 56 patients with
      multisegmental myelopathy who had undergone a C3 to C7 open-door laminoplasty.
      Follow up averaged 5.8 years. Satisfactory neurological improvement occurred in
      73%. Cervical flexion decreased by 35% and extension by 57%; the decrease of both
      movements was statistically significant. Decreased vertebral slip, as well as
      slightly reduced lordosis, was seen after operation. Increase in measured canal
      size after operation and at follow up was 48% and 40%; 8% of the expanded canal
      size was lost at the last follow up. Expansive open-door laminoplasty leads to a
      better neurological prognosis in this group of patients, while maintaining an
      increase in canal size and preserving spinal stability.

PMID- 7649682
TI  - The effect of physeal traction applied to the triradiate cartilage on acetabular
      growth.
AB  - Physeal distraction was applied with an external fixator to the triradiate
      cartilage of dogs with the aim of increasing the capacity of the acetabulum. The
      force was continued for from 2 to 6 weeks and the consequent changes were
      evaluated with regard to function and structure by radiography and microscopy.
      The distraction, without producing epiphysiolysis and destruction of the
      cartilage, resulted in expansion of the pelvic bones. The depth and volume of the
      acetabulum were increased, but the acetabular angle was decreased. Distraction
      also caused proliferation of the lacunar cells and the number of mammillary
      processes in the cartilage columns increased. Distraction can therefore be
      applied to the triradiate cartilage to enlarge the capacity of the acetabulum
      without producing epiphysiolysis.

PMID- 7649684
TI  - M. Jarvinen, A. Natri, M. Lehto, and P. Kannus: reconstruction of chronic
      anterior cruciate ligament insufficiency in athletes using a bone-patellar tendon
      bone autograft. A two-year follow up study.

PMID- 7649683
TI  - [The recent history of substitution procedures for the anterior cruciate
      ligament].
AB  - The evolution of operations to repair or substitute the anterior cruciate
      ligament is summarized for the period 1903 to the present. The increase in the
      understanding of the function of the ligament is described and in the light of
      this experience a programme for the management of these lesions is suggested. In
      acute lesions in a young sportsman the loss of the stability provided by the
      central pivot prevents competition at high level and operation to repair,
      substitute, or reinforce the ligament is recommended. In the older athlete non
      intervention may be acceptable in view of the knowledge that the adverse
      mechanical consequences of a rupture of the ACL may be lessened by appropriate
      rehabilitation. Such measures may be successful for a couple of years, but
      usually, within five years, functional symptoms will appear. In patients who are
      middle aged, or those with no competitive need, rehabilitation only is usually
      adequate, and surgical reconstruction is rarely necessary. In chronic lesions
      operation should probably only be undertaken when instability is a notable
      problem. Reconstruction may be accomplished by an autograft using a bone patella
      bone, semi-membranosis or semi-tendonosis transfer, allograft substitution or a
      prosthesis.

PMID- 7649685
TI  - Informed consent.

PMID- 7649686
TI  - Medial epicondylitis of the elbow.
AB  - Ninety-five cases of medial epicondylitis are reported in 83 patients; 90% were
      related to work and only 10% to sport or leisure activities. Most recovered with
      conservative treatment. Operation was needed in 12%, which compared with under 4%
      of patients with lateral epicondylitis over the same period. The results of open
      release of the common flexor origin were good, with only one exception.

PMID- 7649687
TI  - Total hip replacement with bone grafting using the removed femoral head in severe
      acetabular dysplasia.
AB  - We carried out total hip replacement and femoral head bone-grafting in 21 hips
      with congenital dysplasia or dislocation, obtaining as much support of the cup by
      the host bone as was possible. A Charnley small or extra small cup was implanted
      in 20 cases and a miniature femoral component in 15. The results of 20 hips were
      reviewed prospectively at an average of 10 years. Nineteen patients had no pain.
      Three cups showed radiological signs of loosening, one was causing other
      symptoms. All the stems, except one, were radiologically stable and were
      symptomless. The graft had fused without resorption in 18 cases. Two grafts
      showed severe resorption with loosening of the cup. Satisfactory long term
      results of total hip replacement and femoral head bone-grafting can be achieved
      using special surgical techniques and the appropriate components. Medialisation
      of the hip and the use of small cups are important in allowing sufficient support
      of the prosthesis by bone so that the distribution of load on the graft is
      minimised. The grafted femoral head provides suitable bone stock for
      reconstruction of the acetabulum.

PMID- 7649688
TI  - Cementless total hip arthroplasty with AML, PCA and HGP prostheses.
AB  - Two hundred and fourteen patients who had 270 cementless hip prostheses were
      followed for 2 to 8 years. PCA (Porous-Coated Monatomic), AML (Monatomic
      Medullary Locking) and HGP (Harris-Galante-Porous) femoral stems and acetabular
      cups were used without any preference for the prostheses. The overall clinical
      results were similar for the three prostheses with average Harris hip scores of
      93, 93 and 91 respectively. Four PCA prostheses had radiological aseptic
      loosening and one was revised because of polyethylene wear. There was no
      loosening in the AML and HGP prostheses. Pain in the thigh, usually slight,
      occurred in 17% of AML, 21% of PCA and 19% of HGP prostheses. Five years after
      operation, radiological changes such as migration, calcar remodelling and
      radiolucent lines were the same for the 3 prostheses, but bony ingrowth was
      greater with the AML femoral stems.

PMID- 7649689
TI  - Total hip replacement after intertrochanteric osteotomy.
AB  - From 1980 to 1993 we inserted 216 total prostheses into hips which had been
      treated by varus and valgus-extension intertrochanteric osteotomy. The technique
      of the operation was more difficult than in hips operated on for the first time
      because of anatomical changes produced by the osteotomy in the surrounding
      structures. We have had complications which taught us how to prevent and deal
      with these problems.

PMID- 7649690
TI  - Stress radiography in the diagnosis of anterior cruciate ligament deficiency.
AB  - A prospective study was carried out to test the sensitivity and specificity of
      stress radiography in detecting anterior cruciate ligament deficiency in both
      knees of 116 patients using the Telos device. In 47 of these a total or partial
      rupture of the anterior cruciate ligament was diagnosed by arthroscopy, while the
      ligament was intact in the remaining 69 patients. The mean difference in
      radiological translation between the injured and the normal knee was greater than
      5 mm (p < 0.001) in those with anterior cruciate deficiency, and less than 3 mm
      in the others. A differential displacement of up to 3 mm was considered normal.
      The sensitivity of the method was less than 67% and the specificity was 100%.
      Clinical diagnosis had a sensitivity of 70.2% and a specificity of 98.5%. Our
      findings suggest that, although a differential translation of more than 3 mm can
      be diagnostic, smaller differences do not rule out anterior cruciate deficiency.

PMID- 7649691
TI  - Fixation of the tibial component in knee arthroplasty after six weeks.
AB  - The fixation of cemented and uncemented PCA modular cruciform-stemmed tibial
      components was examined 6 weeks after operation using
      roentgenstereophotogrammetric analysis in 26 randomly selected patients.
      Physiological external forces were applied in external/internal rotation and
      eccentric posterior loading generated by squatting. All cases showed inducible
      displacement, but there were no statistically significant differences between the
      2 groups in inducible displacement or in the initial migration, except for
      subsidence between the lying and standing position. In some, the greatest
      movement was found when changing from resting to standing, or during rotational
      stress; in others, the greatest movement was found during squatting. There was a
      statistical difference in subsidence on squatting which was greater in the
      uncemented group. The design of the cruciform stem and the use of an internally
      cooled saw may explain this small differences between the 2 groups.

PMID- 7649692
TI  - Changes in muscular activity after knee arthrotomy and arthroscopy.
AB  - The object of this study was to find out whether an arthrotomy of the knee would
      damage joint proprioception. Twenty patients who underwent arthrotomy, and 20
      patients after arthroscopy, were tested on a modified ergometer and the
      electromyographic action of their quadriceps and hamstrings recorded. The
      quadriceps action started later and had a shorter duration (20 ms) after
      arthrotomy. The differences are statistically significant in intra-individual
      comparison both for vastus lateralis and medialis, in comparison with the normal
      group for only the vastus medialis. There were no significant differences in
      muscle control after arthroscopy. These results are in favor of preferring
      arthroscopy to arthrotomy whenever possible.

PMID- 7649694
TI  - Etiology and management of anger in groups: a psychodynamic view.
AB  - The author postulates that theoretical explanations of the etiology of anger and
      aggression inform the group therapist's interventions. Four psychodynamic schools
      of thought--drive theory, ego psychology, object relations theory, and self
      psychology--are discussed. Choice of the best-suited theory to increase
      understanding may vary according to the particular patient and/or set of group
      circumstances. A pitfall to be avoided is forcing any given individual, event, or
      process into a specific school of thought. In the group, special issues related
      to anger exist: the therapist's vulnerability to narcissistic injury if made the
      focus of anger, the increased intensity and force of anger that can be mustered
      in a group, and the safety afforded patients as they, outnumbering the
      therapist(s), express anger.

PMID- 7649693
TI  - Revision surgery for lumbar disc herniation. An analysis of 45 patients.
AB  - We reviewed 45 patients who had undergone repeated open operations for lumbar
      disc herniation. There were 26 men and 19 women with a mean follow up of 4.3
      years. Twenty-four patients had had one previous discectomy, 12 had 2, and 9 had
      3 or more; 11 needed a fusion without instrumentation. Residual or re-extruded
      disc hernias, either sub- or transligamentous, were frequently found at revision.
      Good to excellent results were obtained in 64%. Those who had a first-time
      revision had earlier improvement and better results. Complete removal and a
      thorough search for herniated disc material is essential when carrying out the
      initial operation for extruded or sequestrated herniation. At revision, removal
      of as much as possible of the remaining nucleus and annulus, but with minimal
      invasion of the posterior elements, is crucial for improving the outcome.

PMID- 7649695
TI  - Frustration, anger, and the significance of alter-ego transferences in group
      psychotherapy.
AB  - When working with narcissistically vulnerable and angry patients in group
      psychotherapy one must take into account the entire treatment context.
      Interaction takes place among the identified patient, the other members, the
      therapist, and the image of the group as a whole. In members' counter-reactions
      to the difficult person, group-destructive forces frequently are stimulated. The
      offending individual may flee, or the group may reach an impasse in which little
      growth occurs. In this communication, I have focused on alter-ego relationships
      and transferences as a way of understanding aspects of group formation and
      destruction. Angry patients may have intense wishes to be like others and to feel
      part of the human condition. They suffer from feeling alone. Disruption of an
      alter-ego relationship may result in rage. A self-psychological perspective in
      concert with knowledge of group dynamics enables the clinician to formulate ways
      of intervening in problematic group interactions. The therapist's capacity to
      attend to the vulnerabilities of the self of all persons involved in the group is
      often severely tested, particularly under circumstances of emotional contagion.
      Elucidation of twinship and alter-ego transferences may help stabilize difficult
      patients and enable them to restart their psychological growth.

PMID- 7649697
TI  - Discussant comments for special section on anger and aggression in groups.

PMID- 7649696
TI  - Working with anger in groups: a modern analytic approach.
AB  - The development of Modern Psychoanalytic psychotherapy with schizophrenic and
      borderline patients is briefly traced, and the major themes of the treatment
      approach that derived from that early work are discussed with attention to their
      application in group therapy. These themes include the concepts of the
      narcissistic defense, narcissistic transference, joining or reinforcing defenses,
      emotional communication, and a shift away from the classical psychoanalytic
      emphasis on interpretation and insight to a strategy of helping the patient put
      all his or her thoughts and feelings into language in a constructive manner.
      These principles are discussed in connection with three kinds of problems
      involving anger in therapy groups: members' anger destructively turned against
      their own egos, anger expressed toward the leader within a negative transference,
      and anger destructively expressed toward others in the group. Lastly,
      consideration is given to the group leader's anger and its expression within the
      group. Some contrasts are made between the Modern Analytic approach and the
      classical Freudian position as well as Kohut's self psychology.

PMID- 7649698
TI  - Therapist anger in group psychotherapy.
AB  - Countertransference anger serves as a defense against the experience of shame,
      which occurs when therapists fail to live up to jointly created idealized
      expectations. The author describes ways of changing these expectations in order
      to reduce the transference-countertransference resonance, which is based on
      narcissistic needs. The author distinguishes countertransference anger (which
      should not be disclosed to group members) from realistic therapist anger, which
      has therapeutic value. Realistic anger can be used as a therapeutic tool to
      dispel distortions, provide an interpersonal connection, help members trust the
      reality of the situation, and provide a balance of good and bad between the
      members and therapists.

PMID- 7649699
TI  - Brief group treatment and managed mental health care.
AB  - There is increasing interest in the application of brief group psychotherapy to
      treat a wide variety of patient conditions. This paper reviews a selected set of
      controlled and comparison studies of brief, outpatient group treatment with
      adults, and considers findings that support the effectiveness of this approach.
      Authors discuss barriers to the use of brief group interventions and make
      recommendations regarding increased utilization of this approach in managed
      mental health settings.

PMID- 7649700
TI  - A therapy group for mothers with dissociative disorders.
AB  - This paper describes the evolution of a therapy group for mothers with
      dissociative disorders. Although the group is for survivors of childhood trauma,
      its focus is on the present dilemmas of child rearing rather than on past
      traumas. It uses mothering as a common bond to improve parenting and
      interpersonal skills and to propel forward each member's individual therapy. The
      article summarizes the relevant literature, provides a rationale for such a
      group, and discusses the issues of cotherapy, combined therapy, group process,
      transference, countertransference, and thematic material.

PMID- 7649701
TI  - How to work with dreams in psychodrama: developmental therapy from an existential
      dialectical viewpoint.
AB  - As Moreno has shown, the method of psychodrama can be effectively used to work on
      dreams. The first part of this article describes the theoretical framework.
      Special reference is made to a personality model based on self-reflection in
      relation to dialectic processes, existential questions, self-evaluations, and
      personality development. The theoretical introduction is followed by a
      description of the basic elements, techniques, and stages associated with classic
      psychodrama and psychodramatic dream work. After situating this approach in the
      wider context of dream analysis in the field of group therapy, the different
      stages of the working model are illustrated by means of a "dream session"
      conducted with an adolescent therapy group. Finally the session is analyzed from
      the perspective of a number of basic Morenian tenets and from the point of view
      of developmental therapy.

PMID- 7649702
TI  - Blood ammonia response to treadmill and bicycle exercise in man.
AB  - Nine male healthy and physically active volunteers performed four different
      exercise tests: an incremental load exercise test to exhaustion and a constant
      load exercise test of 15 min at 65% VO2max, both on the bicycle ergometer and on
      the treadmill. During the incremental exercise test, blood ammonia levels were
      significantly higher on the bicycle ergometer as compared to the treadmill at the
      same submaximal VO2 (p < 0.05 at 80% of VO2max) and at the VO2max, which was
      identical in the two modes of exercise. Plasma lactate levels were also
      significantly higher on bicycle ergometer at high submaximal exercise intensity
      but not at VO2max. During the constant load exercise test blood ammonia levels
      increased continuously and showed no differences between cycling and running, in
      contrast to plasma lactate accumulation, which was higher on the bicycle
      ergometer. The finding that blood ammonia accumulation during exercise is
      critically dependent upon the test procedure has to be taken into account
      whenever blood ammonia measurements are used in the physiological monitoring of
      athletes.

PMID- 7649703
TI  - Effects of short-term maximal work on plasma calcium, parathyroid hormone,
      osteocalcin and biochemical markers of collagen metabolism.
AB  - Physical activity is most probably an important factor to increase bone mass. The
      exact mechanisms by which this takes place are not completely understood. During
      the last years methods have become available making it possible to study the
      metabolism of type I collagen in bone in more detail. In this study seven male
      athletes were studied before and after a short-term maximal work (a modified
      Wingate test at a retardation of 7.5% of body weight) during 30 seconds. Blood
      samples were drawn before the test and 5 and 60 minutes after. Serum
      concentrations of type I procollagen carboxyterminal propeptide (PICP) and
      carboxyterminal telopeptide of type I collagen (ICTP) were measured, as were
      serum calcium, parathyroid hormone and osteocalcin. Serum PICP and ICTP reflect
      synthesis and degradation of type I collagen, respectively and mainly bone
      collagen metabolism. A significant increase of ionized calcium and lactate was
      noted while PTH and total serum calcium did not change. No significant
      alterations of either ICTP, PICP or osteocalcin were registered. We conclude from
      this study that the short-term maximal work performed by means of the modified
      Wingate test failed to show any significant changes in bone metabolism
      (osteocalcin and metabolites of type I collagen). A short experimental period and
      lactacidosis might contribute to the unaltered bone metabolism. The results
      mainly indicate that there is no pool of bone biochemical markers in young
      athletic males that is washed out by short bursts of intense exercise.

PMID- 7649704
TI  - Does increased serum creatine kinase activity reflect exercise-induced muscle
      damage in rats?
AB  - To test a hypothesis that exercise-induced increase in serum creatine kinase
      activity and the concomitant necrotic muscle damage in unaccustomed rats may be
      interrelated phenomena, and that the first might largely be caused by changes in
      lymph flow, groups of rats were separately exposed to a swimming, combination of
      swimming and running, and running protocol. Their serum was then repeatedly
      analysed over a period of 72 h for creatine kinase activity, and their soleus and
      the red parts of quadriceps femoris muscles for beta-glucuronidase activity
      (damage marker) 72 h after the commencement of the experiment, i.e. at a moment
      when muscle damage is in the necrotic phase. The results clearly showed that
      serum creatine kinase activity may increase without concomitant muscle damage
      (swimming protocol) and that muscle damage may occur without a statistically
      significant increase in serum creatine kinase activity (running protocol).
      Swimming followed by running increased creatine kinase activity more strongly
      than the separate protocols. Muscle damage was of a similar magnitude after
      running and after the combined exercise. The present results indicate that serum
      creatine kinase activity in rodent exercise myopathy is an inadequate indicator
      of injury both quantitatively and qualitatively.

PMID- 7649705
TI  - Serum amino acid concentrations in nine athletes before and after the 1993 Colmar
      ultra triathlon.
AB  - The amino acid imbalance hypothesis should explain the fatigue originating in the
      brain during sustained exercise or over-training as a branched-chain
      (BCAA)/aromatic amino acids (AAA) imbalance with increased brain tryptophan
      uptake and 5-hydroxytryptamine synthesis. The serum amino acid profile was
      determined in 9 ultra-triathletes before and after completing the 1993 Colmar
      ultra-triathlon to additionally analyse the extent of this amino acid imbalance
      during such an extreme prolonged contest lasting more than 23 hours. The summed
      serum concentration of 25 amino acids decreased by 18% from 3962 +/- 846 to 3255
      +/- 694 umol.l-1 likely reflecting a catabolic state of the organism with a
      decrease in 18 individual amino acids by 9-56%, an increase in cystine (+38%),
      methionine (+24%), tyrosine (+10%), phenylalanine (+12%), free tryptophan (+74%),
      and constant glutamine, leucine and total tryptophan levels. Since plasma volume
      increased by approximately 7.6% with a 3.3 kg body mass decrease in the athletes
      during the ultra triathlon, a decrease in intra-cellular water with an extra
      cellular fluid increase is hypothesized. This decrease in cellular hydration
      state is seen as a protein-catabolic signal.

PMID- 7649706
TI  - Ultrastructural modification of human skeletal muscle tissue with 6-month
      moderate-intensity exercise training.
AB  - The study was aimed at investigating if endurance training of moderate intensity
      and longer duration, intended to promote health rather than performance, evokes
      ultrastructural changes in skeletal muscle tissue comparable to those observed
      after high-intensity protocols. Twenty healthy, middle-aged men enrolled in a 6
      month, home-based jogging program of 120 min/wk at 75% VO2max. Only 12 men showed
      a sufficient exercise adherence over the 6 months (> or = 60 min/wk on average)
      and were included into statistical analysis. Their average training activity was
      105 +/- 31 min/wk. The results revealed significant increases in VO2max (+8.4%, p
      < 0.01) and submaximal power output (+18.1%, p < 0.01). Total mitochondrial
      volume density in M. vastus lateralis increased by 20% (p < 0.05) with a larger
      increase in subsarcolemmal volume compared to central volume (50% vs 15%). No
      changes in volume of intracellular lipid droplets, capillary density, capillary
      per fiber ratio, fiber mean cross-sectional area and muscle fiber type could be
      observed. Body composition analysis showed a decrease in trunk fat mass (-7.3%, p
      < 0.05) and an increase in trunk lean mass (+1.7%, p < 0.05), while changes in
      the legs were not significant. It can be concluded that a moderate-intensity,
      health oriented endurance training beneficially affected cardiovascular and
      muscle oxidation capacity as well as body composition in the trunk area. No
      adaptations in capillaries or lipid metabolism could be demonstrated. The results
      support the hypothesis of thresholds for induction of adaptation processes in
      muscle skeletal tissue depending on the intensity of the exercise stimulus.

PMID- 7649707
TI  - The effects of dichloroacetate on lactate accumulation and endurance in an
      exercising rat model.
AB  - Severe lactic acidosis usually accompanies intense endurance exercise. It has
      been postulated that glycogen depletion working in concert with elevated muscle
      and plasma lactate levels lead to a concomitant reduction in pH. Their cumulative
      effect during prolonged physical exertion now leads to muscular fatigue and
      eventually limit endurance capacity. Therefore in the present study,
      dichloroacetate (DCA), a compound which enhances the rate of pyruvate oxidation
      thus reducing lactate formation, has been evaluated in a validated rat model of
      sub-maximal exercise performance. Male rats (350 g) were divided into two groups
      (control-saline, i.v. and DCA 5 mg/kg, i.v.) and were exercised to exhaustion in
      a chamber (26 degrees C) on a treadmill (11 m/min, 6 degrees incline). When
      compared to controls, the DCA-treated rats had longer run times (169 vs 101 min)
      and a decreased heating rate (0.020 vs 0.029 degrees C/min). In addition, DCA
      attenuated the increase in plasma lactate (28 vs 40 mg/dl) and significantly
      reduced both the rate and absolute amount of depletion of muscle glycogen stores.
      These results suggest that the activation of pyruvate dehydrogenase activity by
      DCA resulted in a reduction in the rate of glycogenolysis in addition to
      decreasing lactate accumulation by presumably limiting the availability of
      pyruvate for conversion to lactate, therefore increasing muscle carbohydrate
      oxidation via the TCA cycle. Thus DCA effected a significant delay in muscle
      fatigue.

PMID- 7649708
TI  - The importance of ATPase microenvironment in muscle fatigue: a hypothesis.
AB  - A broadly held opinion is that fatigue is not due to an insufficient supply of
      ATP to the energy consuming mechanisms because tissue [ATP] always remains at
      least one order of magnitude higher than Km for ATP of any ATPase. In general
      these findings also suggest that ATP consumption is well balanced with ATP
      regeneration even in the fatigued muscles. This balance is achieved by down
      regulation of ATP consumption. Potentially this down-regulation could be
      accomplished by any product of the ATPase reaction and the role of Pi and H+
      accumulation in this regulation has been discussed in the literature. The purpose
      of this paper is to describe known compartmentalization of ATP regeneration
      systems in muscle cell, their importance in the regulation of [adenine
      nucleotide] in the vicinity of ATPases and how such local ATP regeneration maybe
      important in the etiology of muscle fatigue. Available experimental evidence
      suggests that the binding of creatine kinase and glycolytic enzymes in the
      vicinity of sites where ATP is hydrolyzed and functional coupling between these
      ATP regenerating mechanisms and ATPase can generate ATPase microenvironments that
      have an important role in the regulation of ATPase function. Main function of
      this ATP regeneration is to keep the local ADP/ATP ratios favorable for ATPase
      function, which seems to be especially important when ATPase turnover is high.
      Unfortunately, the maximum rate of local ATP regeneration relative to that of ATP
      hydrolysis in vivo is not known, mainly because in vitro determinations
      underestimate this value due to a decrease in the fractional of loosely abound
      enzyme to the preparation during isolation procedure.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7649709
TI  - Run training vs cross training: influence of increased training on running
      economy, foot impact shock and run performance.
AB  - The purpose of the study was to compare changes in running economy, foot impact
      shock, run performance, and resting heart rate and blood pressure elicited by
      increases in training volume via run training (RT) and cross training (CT). After
      30 d of normal training (NT), male runners (N = 11) completed two 10 d periods of
      increased training each preceded by 14 d of reduced training (80% NT). Subjects
      ran 10 consecutive days in the afternoon (100% of NT) and performed 8 additional
      workouts in the morning (100% of NT). The morning sessions were performed on a
      cycle ergometer (CT) or a treadmill (RT). Running economy, foot impact shock and
      lactate were assessed during submaximal running (3.9 +/- 0.06 m.sec-1) at D0 and
      D11. Following the submaximal run, subjects completed a simulated 5 km race on a
      treadmill. VO2 during the running economy test was significantly higher at D11 of
      CT (52.5 +/- 1.5) compared to RT (51.1 +/- 1.4 ml.kg-1.min-1). RER, carbohydrate
      oxidation, and lactate were significantly lower; whereas, foot impact shock was
      significantly higher following both training modes. No significant changes in run
      performance, resting heart rate and blood pressure occurred during the study. In
      summary, 10 d of increased training resulted in a reduced running economy for CT,
      and a lower carbohydrate oxidation and an increase in foot impact shock for both
      training modes.

PMID- 7649710
TI  - Recovery of dynamic muscle function following isokinetic fatigue testing.
AB  - This study was designed to evaluate recovery of dynamic muscle function following
      muscle fatigue produced by isokinetic testing. Sixteen physically active males
      (age = 29.2) performed fatigue and recovery tests on an isokinetic dynamometer
      (KIN-COM 500H). The fatigue test involved concentric contractions of the
      quadriceps femoris performed until force output fell below 50% MVC for 3
      consecutive contractions. This test was repeated 3 times, with 1 minute rest
      between sets. Recovery of force output was measured during the following 8
      minutes. Following post hoc analysis, subjects were grouped into 1 of 3 groups
      based on their time to recovery of 80% MCV; Recovery immediately following
      fatigue exercise (Group 1), between 3 and 6 minutes (Group 2), or no recovery
      during the 8 minute period (Group 3). Analysis revealed a significant decline in
      peak force between bouts of a three-bout fatigue test for Groups 2 and 3 (p <
      0.001), and no decline in Group 1. There was a significant relationship between
      decline in force output and time to recovery. Thus, subjects developing a greater
      amount of muscle fatigue took longer to recover following this isokinetic test.
      It was concluded that an isokinetic fatigue test to 50% MVC, repeated 3 times, is
      an appropriate fatigue generating protocol for most active males; that recovery
      time following isokinetic fatigue exercise varies among active males; and
      recovery may be directly related to decline in force output between bouts of a
      three-bout fatigue test.

PMID- 7649711
TI  - Effect of drafting on work intensity in classical cross-country skiing.
AB  - The purpose of this study was to compare the heart rate responses during cross
      country skiing as a leading skier, as well as in a drafting situation, three
      meters behind the leader. Eight male and two female cross-country ski racers,
      paired for skiing ability, skied a 2 km course (two loops of 1 km) using the
      diagonal stride and double-poling techniques at a fixed speed (4.75 m.s-1 and
      4.45 m.s-1 for males and females respectively) on two different occasions, once
      as a leading skier, the other as a drafter. A recovery period of 30 minutes was
      allowed between the two trials. Heart rates (HR) were registered every five
      seconds during all performances. Results revealed that HR were significantly
      lower (165 vs 172 beats.min-1) when skiing behind another skier as opposed to
      leading. Results also revealed that projected frontal areas appeared to influence
      the effects of drafting such that the HR differences between the leading and the
      drafting situations were larger for smaller skiers drafting behind larger skiers.
      These results showed that skiing behind another skier in a classical cross
      country ski race would be very advantageous when the situation is encountered and
      could help racers using this energy saving strategy.

PMID- 7649712
TI  - Glycosaminoglycan polysulfate injections in lateral humeral epicondylalgia: a
      placebo-controlled double-blind trial.
AB  - The purpose of this study was to investigate the therapeutic benefit of local
      Glycosaminoglycan polysulfate (GAGPS) injections in the treatment of chronic
      epicondylalgia. The study was conducted as a prospective, placebo-controlled
      double-blind trial. Sixty patients with a typical history of pain for at least 3
      months who attended two private orthopaedic clinics in Stockholm received 50 mg
      GAGPS or placebo injections, one injection a week, for five weeks. The main
      outcome measures were the patients' evaluation of pain in connection with daily
      activities with a visual analogue scale and the number of treatment failures. The
      follow-up period was six months. The difference in reduction of painscore (VAS)
      ranging between 11.1 percentage units at the half-year follow-up and 20.9
      percentage units 2 weeks after the treatment period is clinically good. The
      number of treatment failures in the GAGPS treatment groups at the 6 week follow
      up was only 4 (13%) compared with 12 (40%) of the placebo treated patients. At
      the half-year follow-up 5 of those who received GAGPS had experienced a
      recurrency. The recurrency rate is thus smaller than most of those reported in
      controlled studies with corticosteroids. In the GAGPS treated group 13 patients
      reported on local pain after some injections, 2 cases combined with local
      haematomas, compared with 5 cases of local pain in the placebo group. The results
      confirm previous good results of GAGPS injection therapy in subchronic and
      chronic peritendinitis.

PMID- 7649713
TI  - An epidemiological analysis of overuse injuries among recreational cyclists.
AB  - Two-hundred and ninety-four male and 224 female randomly selected recreational
      cyclists responded to a mail questionnaire. Significant differences were observed
      between male and female cyclists' training characteristics. Overall, 85% of the
      cyclists reported one or more overuse injury, with 36% requiring medical
      treatment. The most common anatomical sites for overuse injury/complaints
      reported by the male and female cyclists combined were the neck (48.8%), followed
      by the knees (41.7%), groin/buttocks (36.1%), hands (31.1%), and back (30.3%).
      For the male cyclists, effect upon back and groin/buttocks overuse
      injuries/complaints were miles/week, lower number of gears, and less years of
      cycling. For female cyclists, training characteristics which had the most
      significant effect upon groin/buttocks overuse injury/complaints were more non
      competitive events/year and less stretching before cycling. The odds of female
      cyclists developing neck and shoulder overuse injury/complaints were 1.5 and 2.0
      times more, respectively than their male counterparts.

PMID- 7649714
TI  - Medical use of psychostimulants: an overview.

PMID- 7649715
TI  - Hospital stressors experienced by elderly medical inpatients: developing a
      Hospital Stress Index.
AB  - OBJECTIVE: To develop a long and short version of an index to measure experiences
      during hospitalization perceived by elderly patients as stressful. SAMPLES AND
      METHODS: Consecutive patients aged sixty or over admitted to a university
      teaching hospital were assessed for hospital-related stressors during two
      separate studies. In the first study, seventy-six patients were asked an open
      ended question exploring what they found most stressful about being in the
      hospital. Responses were grouped into major categories, and questions were
      developed to address concerns in each category; the resulting forty items were
      called the Hospital Stress Index (HSI). The HSI was then administered to a
      separate group of ninety-two patients; data were also collected on functional
      disability (impaired ADLs), dysfunctional attitudes (DAS), and depressive
      symptoms (CES-D). RESULTS: Spontaneously reported hospital stressors were grouped
      into seven categories: 1) adverse effects of diagnostic or therapeutic
      procedures/treatments, 2) forced life-style changes, 3) relationships with staff,
      4) individual psychiatric issues, 5) understanding diagnosis/prognosis, 6) family
      issues, and 7) the physical environment. The largest category of stressors
      concerned relationships with doctors and nurses. High HSI scores were
      significantly more common among Whites than Blacks and among patients with high
      CES-D, high DAS, or impaired ADLs scores. A number of potentially modifiable
      hospital-related stressors and individual patient issues were identified.
      Finally, an abbreviated fifteen-item HSI was developed to maximize patient
      discriminability, highlight individual differences, and enhance the detection of
      modifiable stressors. CONCLUSIONS: Hospital-reported stressors may contribute to
      the emotional distress that elderly inpatients experience. We have developed an
      index to identify such stressors.

PMID- 7649716
TI  - The use of methylphenidate for cognitive decline associated with HIV disease.
AB  - OBJECTIVE: Complaints of cognitive changes are often expressed by patients at all
      stages of HIV infection. Such changes include decreased memory and attention
      span, diminished concentration, apathy, and "slowing." Methylphenidate (MPD) has
      been used in several clinical studies in men with late-stage HIV disease in an
      attempt to ameliorate these difficulties. The objectives of this review article
      are to review salient psychopharmacological characteristics of MPD and to
      describe the research and clinical literature supporting the use of MPD in
      patients at all stages of HIV infection. METHODS: Seven studies, case reports, or
      abstracts from International Conferences on AIDS were available in the English
      literature through August, 1993, directly addressing the use of MPD in patients
      with HIV disease. Twenty-nine papers were reviewed for pharmacokinetic data,
      eighteen for safety and side effects issues, and seventeen for relevant
      contributions from the neuropsychological testing literature. RESULTS: Studies in
      clinical settings have used doses ranges from 10-90 mg. per day in two or three
      divided doses with reportedly good results in improving both affective and
      cognitive symptoms associated with HIV disease. Side effects have been relatively
      mild and patient satisfaction with treatment has been high. However, no studies
      have been conducted in early stage HIV disease, where a significant minority of
      patients have similar complaints in the absence of clinically apparent
      immunosuppression. Likewise, placebo-controlled, dose-finding studies in AIDS
      patients are entirely lacking, and no studies in women with HIV disease and
      cognitive changes have been published. CONCLUSIONS: In spite of these important
      research short-comings, clinical experience with MPD treatment of cognitive
      changes in men with HIV/AIDS is consistent with the notion that this medication
      holds significant promise to improve the quality of life for persons living with
      HIV/AIDS. Controlled studies to test this hypothesis are warranted.

PMID- 7649717
TI  - Neuropsychiatric sequelae of stroke and traumatic brain injury: the role of
      psychostimulants.
AB  - OBJECTIVE: The primary purpose of this article is to review certain
      neuropsychiatric sequelae of stroke and traumatic brain injury (TBI), and the
      role of the psychostimulants methylphenidate (MPD) and dextroamphetamine (DAMP)
      in their treatment. METHOD: A general review of the topic is presented.
      Controlled and uncontrolled studies involving the use of the psychostimulants are
      discussed. These consist of 11 studies listed with Medline 2000 that deal
      specifically with stroke or head injury, with the oldest study reviewed dating
      back to 1984. Studies concerning the use of psychostimulants in the medically or
      neurologically ill are reviewed to the extent that they are pertinent. RESULTS:
      The current literature consists primarily of uncontrolled case studies. However,
      these are reviewed and found to suggest a role for the use of the
      psychostimulants, which is discussed. CONCLUSIONS: In general, these drugs appear
      to be a reasonable treatment choice for certain types of mood, behavior, and
      cognitive symptoms following brain injury. However, it is noted that larger scale
      controlled studies are needed to adequately assess the clinical usefulness of
      these drugs.

PMID- 7649718
TI  - Effects of methylphenidate in HIV-related depression: a comparative trial with
      desipramine.
AB  - This report is a randomized, double-blind, comparative trial of desipramine with
      the psychomotor stimulant methylphenidate. Twenty HIV antibody-positive patients
      with depressive symptoms were randomly assigned to either drug. After individual
      dose titration, the mean daily dose of desipramine was 150 mg. and
      methylphenidate 30 mg. daily. The differences in responses between desipramine
      and methylphenidate were not statistically significant on various measures of
      depression. The antidepressant effect of methylphenidate did not occur any faster
      than that of desipramine. Both significantly reduced depressive and anxious
      symptomatology over the blinded portion of the treatments. Thus, methylphenidate
      relieves depressive symptomatology with efficacy similar to that of desipramine,
      offering an alternative to patients who are unable to tolerate standard tricyclic
      antidepressant therapy. The dopaminergic effects of methylphenidate are likely to
      mediate its antidepressant effects.

PMID- 7649719
TI  - Toxicity and abuse of prescribed stimulants.
AB  - Concerns about the toxicities of psychomotor stimulants originate primarily from
      effects seen at high doses, when stimulants are abused. Low dose use in the
      apathetic medically ill patient has been generally associated with only minimal,
      short lived side effects, which are detailed herein. Confusion may be worsened in
      already delirious patients. Anxiety, psychosis, cardiovascular effects, insomnia,
      and tremor may occur but infrequently require discontinuation. Appetite is
      normally stimulated in the medically ill. In fact, stimulants are frequently
      utilized in the medically ill largely because of their minimal toxicity. The
      history of U.S. stimulant abuse in the twentieth century is briefly discussed.
      Abuse of prescribed stimulants appears to be infrequent. Over-zealous concern
      regarding abuse has previously led to unfortunate declines in appropriate
      utilization of stimulants, e.g., for attention deficit disorder. Guidelines for
      prescribing stimulants in light of abuse potential are included.

PMID- 7649720
TI  - Development, reliability and validation of the Diabetes Emotional Adjustment
      Scale in Spanish: preliminary findings.
AB  - OBJECTIVE: The development of instruments to measure emotional maladjustment in
      diabetic Hispanic populations has received little attention. We present the
      development and validation of the Diabetes Emotional Adjustment Scale in Spanish.
      METHOD: An eighteen-item self-administered scale was construed to assess
      emotional adjustment in Spanish-speaking diabetic patients and the psychometric
      properties of the scale were assessed. The scale was applied to a sample of sixty
      patients and scale scores were correlated with scores on a battery of Spanish
      versions of established measures of psychological distress, to assess concurrent
      validity. Test-retest reliability was established four years later re-examining
      thirty-eight of the initial sixty-patients sample. RESULTS: Split-half
      reliability and test-retest reliability were satisfactory. There were significant
      correlations between the scale results and measures of depression, trait-anxiety,
      family adjustment, and locus of control of behavior. A principal component
      analysis with varimax rotation yielded a six-factor solution explaining 50.4
      percent of the total variance. CONCLUSIONS: The scale is useful as a screening
      instrument, but the confirmation of factor structure stability and the
      correlation of the scale results with objective measures of metabolic control,
      require further investigation.

PMID- 7649721
TI  - Personality neuroticism and depression after stroke.
AB  - AIM: The aim of this study was to determine whether personality neuroticism or
      extroversion traits are associated with post-stroke depression. METHOD: Ninety
      four stroke inpatients undergoing rehabilitation were examined two months post
      stroke for the presence and severity of depression and a retrospective assessment
      was made of life-time neuroticism and extroversion. RESULTS: Depressed patients
      (N = 35) had higher neuroticism scores than non-depressed patients. Neuroticism
      was correlated positively with depressive symptomatology. Extroversion was not
      associated with depression diagnosis or depressive symptomatology. CONCLUSION: We
      conclude that personality neuroticism may be a risk factor for depression
      following stroke.

PMID- 7649722
TI  - Nursing education trends in the Caribbean.
AB  - Today, the professional nurse must be educated to respond to and manage the
      present and forecasted advances in the health system. They must be innovative,
      analytical and articulate, which cannot be taught using the traditional
      apprenticeship methods. Nursing workforce development must of necessity be broad
      in scope to encompass the socioeconomic, political and health system changes.
      These changes and trends significantly affect nursing generally, and nursing
      education specifically.

PMID- 7649723
TI  - Denmark supports nursing education in Lithuania.
AB  - Since 1993 the Danish Nurses' Organization (DNO) has been helping Lithuanian
      nurses to develop a new nursing curriculum and regulatory system. Lise Kaalund
      Jorgensen, DNO's project coordinator, reports on the progress.

PMID- 7649724
TI  - Ethical climate in health care organizations.
AB  - An organization's policies, procedures and practices on ethical issues can
      influence the amount of risk nurses will take in voicing their opinions about
      patient care issues. While the concepts of organizational climate and culture are
      frequently referred to, the concept of ethical climate is relatively new.

PMID- 7649725
TI  - How Swiss nurses work at the local level.
AB  - In such decentralized federal systems as Switzerland, where regional entities
      have their own laws and are vested with many responsibilities, nurses'
      associations generally operate in the same manner. Below, how the Swiss Nurses'
      Association works with its branches and prepares its nurses to work at the local
      level.

PMID- 7649726
TI  - Organ & tissue donation.

PMID- 7649727
TI  - Your help is needed!

PMID- 7649728
TI  - Death, dying and Iowa law.

PMID- 7649729
TI  - Latex allergy.

PMID- 7649730
TI  - Thyrotoxic periodic paralysis.

PMID- 7649731
TI  - Are you afraid of death?

PMID- 7649732
TI  - What's in a name?

PMID- 7649733
TI  - The dispersion of genetic technologies and the law.

PMID- 7649734
TI  - Commerce and genetic diagnostics.

PMID- 7649735
TI  - Human growth hormone. A case study in treatment priorities.

PMID- 7649736
TI  - Shaping priorities in genetic medicine.

PMID- 7649737
TI  - Screening policy for cystic fibrosis. The role of evidence.

PMID- 7649738
TI  - Physician-assisted suicide and the profession's gyrocompass.

PMID- 7649739
TI  - Selling death and dignity.
AB  - Advocates use case descriptions to show that euthanasia or assisted suicide is
      sometimes justifiable. Yet even the seemingly clearest cases can prove deeply
      troubling.

PMID- 7649740
TI  - Embryo research revisited.

PMID- 7649741
TI  - But is it assisted suicide?

PMID- 7649742
TI  - Punishing medicine.

PMID- 7649743
TI  - Futility and hospital policy.

PMID- 7649744
TI  - Conflicts of conscience. Hospice and assisted suicide.
AB  - Proposals to legalize assisted suicide challenge hospice's identity and
      integrity. In the wake of Measure 16, Oregon hospice programs must develop
      practical policies to balance traditional commitments not to hasten death and not
      to abandon patients with dying patients' legal right to request lethal
      prescriptions.

PMID- 7649745
TI  - Women and HIV: a new agenda.

PMID- 7649746
TI  - In the courts.

PMID- 7649747
TI  - Society's choices.

PMID- 7649748
TI  - Professional integrity and physician-assisted death.
AB  - The practice of voluntary physician-assisted death as a last resort is compatible
      with doctors' duties to practice competently, to avoid harming patients unduly,
      to refrain from medical fraud, and to preserve patients' trust. It therefore does
      not violate physicians' professional integrity.

PMID- 7649749
TI  - Longitudinal patterns of medical service use and costs among people with AIDS.
AB  - OBJECTIVE: This study examines the effect of race, HIV transmission group, and
      decedent status on the use and cost of inpatient and outpatient care among people
      with AIDS. DATA SOURCES: Data come from 914 people with AIDS who were receiving
      services in nine cities across the United States in 1990-1991 and who indicated
      that a hospital clinic was their usual source of care. Review of hospital medical
      and billing records provided data on use and costs of medical services over an 18
      month period. Vital status was determined from hospital records and death
      certificates. STUDY DESIGN: Data from each respondent were aggregated into three
      month intervals, beginning with the last quarter of data and working backward.
      Regression analyses using random-effect models and generalized estimating
      equations were conducted to assess temporal patterns of inpatient and outpatient
      use and costs. PRINCIPAL FINDINGS: Inpatient utilization and costs were higher
      for decedents than for nondecedents. However, differences between decedents and
      nondecedents varied as a function of race. Nonwhites had more inpatient use and
      higher costs than whites, but lower outpatient use, and these differences were
      greater among decedents. Inpatient nights and costs rose sharply in the six
      months prior to death. Outpatient use and costs did not display as strong a
      temporal trend. CONCLUSIONS: Much of the cost of treating HIV infection is
      concentrated in the period immediately preceding death. The intensity of service
      use in the terminal period should be considered when developing estimates of
      annual costs of care and when designing programs to provide community-based
      treatment.

PMID- 7649750
TI  - Correlation of rates of coronary artery bypass surgery, angioplasty, and cardiac
      catheterization in 305 large communities for persons age 65 and older.
AB  - OBJECTIVE: The rate of coronary artery bypass surgery (CABG) has been shown to
      vary greatly across geographic regions. This study examined whether these rates
      were associated with the rate of coronary artery angioplasty (PTCA) and with
      other community characteristics. DATA SOURCES/STUDY SETTING: The health care
      financing administration provided the number of Medicare hospitalizations in 1988
      for conditions and procedures related to coronary artery disease. Information on
      physicians and hospitals was obtained from the Area Resource File, and the number
      of persons in each age, sex, and race category was obtained from US. census data.
      STATISTICAL METHODS: Age-and sex-adjusted hospitalization rates based on the
      patient's zip code of residence were calculated at the level of the Metropolitan
      Statistical Area (MSA) for white patients age 65 or older. Rates were obtained
      for 305 MSAs for CABG, PTCA, cardiac catheterization, angina, and myocardial
      infarction. PRINCIPAL FINDINGS: The rate of cardiac catheterization had a
      correlation of .72 with the CABG rate and .64 with the PTCA rate. The correlation
      of the PTCA and CABG rates with each other was .49. This correlation was not
      charged by adjusting for the rates of hospitalization for angina or myocardial
      infection, but it was reduced to only .05 (ns) after adjusting for the rate of
      cardiac catheterization. The rates of all three procedures had rank correlations
      of about .15 with the density of thoracic surgeons and about .30 with the density
      of hospitals with cardiac catheterization and open heart surgery units.
      CONCLUSIONS: Community CABG and PTCA rates tend to move in the same direction due
      to community factors that also affect the rates of cardiac catheterization. These
      community factors do not appear to include the rate of coronary artery disease,
      but may include resources or attitudes toward aggressive treatment of coronary
      artery disease.

PMID- 7649751
TI  - Hospital adoption of medical technology: an empirical test of alternative models.
AB  - OBJECTIVE: This study examines hospital motivations to acquire new medical
      technology, an issue of considerable policy relevance: in this case, whether,
      when, and why hospitals acquire a new capital-intensive medical technology,
      magnetic resonance imaging equipment (MRI). STUDY DESIGN: We review three common
      explanations for medical technology adoption: profit maximization, technological
      preeminence, and clinical excellence, and incorporate them into a composite
      model, controlling for regulatory differences, market structures, and
      organizational characteristics. All four models are then tested using Cox
      regressions. DATA SOURCES: The study is based on an initial sample of 637
      hospitals in the continental United States that owned or leased an MRI unit as of
      31 December 1988, plus nonadopters. Due to missing data the final sample
      consisted of 507 hospitals. The data, drawn from two telephone surveys, are
      supplemented by the AHA Survey, census data, and industry and academic sources.
      PRINCIPAL FINDING: Statistically, the three individual models account for roughly
      comparable amounts of variance in past adoption behavior. On the basis of
      explanatory power and parsimony, however, the technology model is "best."
      Although the composite model is statistically better than any of the individual
      models, it does not add much more explanatory power adjusting for the number of
      variables added. CONCLUSIONS: The composite model identified the importance a
      hospital attached to being a technological leader, its clinical requirements, and
      the change in revenues it associated with the adoption of MRI as the major
      determinants of adoption behavior. We conclude that a hospital's adoption
      behavior is strongly linked to its strategic orientation.

PMID- 7649752
TI  - Strategic responses by hospitals to increased financial risk in the 1980s.
AB  - OBJECTIVE: This research addresses the following types of responses by hospitals
      to increased financial risk: (a) increases in prices to privately insured
      patients (testing separately the effects of risk from the effects of "cost
      shifting" that depends on level of Medicare payment in relation to case mix
      adjusted cost); (b) changes in service mix offered and selectivity in acceptance
      of patients to reduce risk; and (c) efforts to reduce variation in resource use
      for those patients admitted. DATA SOURCES: The database includes a national panel
      of over 400 hospitals providing information from patient discharge abstracts,
      hospital financial reports, and county level information over the period 1980
      1987. STUDY DESIGN: Econometric methods suitable to panel data are implemented,
      with tests for pooling, hospital-specific fixed effects, and possible problems of
      selection bias. PRINCIPAL FINDINGS: The prices paid by private insurers to a
      particular hospital were affected by the changes in risk imposed by Medicare
      prospective payment, the generosity of Medicare payment, state rate regulation,
      and ability of the hospital to bear risk. The risk-weighted measure of case mix
      did not respond to changes in payment policy, but other variables reflecting the
      management of care after admission to reduce risk did change in the predicted
      directions. CONCLUSIONS: Some of the findings in this article are relevant to
      current Medicare policies that involve risk-sharing, for instance, special
      allowances for "outlier" patients with unusually high cost, and for sole
      community hospitals. The first type of allowance appears successful in preserving
      access to care, while the second type is not well justified by the findings.
      State rate regulation programs were associated not only with lower hospital
      prices but also with less risk reduction behavior by hospitals. The design of
      regulation as a sort of risk-pooling arrangement across payers and hospitals may
      be attractive to hospitals and help explain their support for regulation is some
      states.

PMID- 7649753
TI  - Are PRO discharge screens associated with postdischarge adverse outcomes?
AB  - OBJECTIVE: We evaluate whether patient outcomes may be affected by possible
      errors in care at discharge as assessed by Peer Review Organizations (PROs). DATA
      SOURCES/STUDY SETTING: The three data sources for the study were (1) the generic
      screen results of a 3 percent random sample of Medicare beneficiaries age 65
      years or older who were admitted to California hospitals between 1 July 1987 and
      30 June 1988 (n = 20,136 patients); (2) the 1987 and 1988 California Medicare
      Provided Analysis and Review (MEDPAR) data files; and (3) the American Hospital
      Association (AHA) 1988 Annual Survey of Hospitals. STUDY DESIGN: Multivariate
      logistic regression analysis was used to evaluate the association between the
      results of generic discharge administered by the PROs and two patient outcomes:
      mortality and readmission within 30 days. The analysis was adjusted for other
      patient characteristics recorded on the uniform discharge abstract. PRINCIPAL
      FINDINGS: Four discharge screens indicated an increased risk of an adverse
      outcome-absence of documentation of discharge planning, elevated temperature,
      abnormal pulse, and unaddressed abnormal test results at discharge. The other
      three discharge screens examined-abnormal blood pressure, IV fluids or drugs, and
      wound drainage before discharge-were unrelated to postdischarge adverse outcomes.
      CONCLUSIONS: Generic discharge screens based on inadequate discharge planning,
      abnormal pulse, increased temperature, or unaddressed abnormal tests may be
      important indicators of substandard care. Other discharge screens apparently do
      not detect errors in care associated with major consequences for patients.

PMID- 7649754
TI  - Cytogenetic peculiarities in the Algerian hedgehog: silver stains not only NORs
      but also heterochromatic blocks.
AB  - Hedgehogs belong to one of the several mammalian taxa in which karyotype
      differences are based on variations in heterochromatin content. Furthermore, the
      number and location of nucleolar organizer regions (NORs) can also vary widely.
      In the present study these cytogenetic features were investigated in the Algerian
      hedgehog, Erinaceus (Aethechinus) algirus. The heterochromatin and NOR
      distribution patterns in the karyotype of this species are new among hedgehogs,
      whereas the euchromatic regions, including their G-band pattern, are similar to
      those reported by others. In addition, silver staining revealed a cytogenetic
      feature exclusive to the heterochromatic blocks of E. algirus: their silver
      staining with standard cytogenetic procedures. Because no similar phenomenon has
      been described previously in a mammalian species, several hypotheses about the
      significance and specificity of silver staining to NOR sites are discussed.
      Finally, the existence of different types of heterochromatin in the species
      analysed here, lead us to propose that what hedgehogs have inherited from their
      common ancestor is a mechanism which permits the accumulation of heterochromatin
      on specific chromosomes, rather than the heterochromatin itself.

PMID- 7649755
TI  - Nonindependence of matches at different loci in DNA profiles: quantifying the
      effect of close relatives on the match probability.
AB  - In comparing a particular DNA profile with that from an unknown (but distinct)
      individual, matches at different loci between the profiles will not be
      independent, even in a randomly mating population, because of the presence in the
      population of relatives of the individuals. The paper contains a theoretical
      analysis of the extent of this effect on the match probability, for profiling
      techniques which separately probe different loci. Naive calculation using the
      product rule could substantially understate the match probability. Past a certain
      point, the testing of additional loci provides no more information than would be
      available in discriminating between sibs. The correlation effect described here
      would be unimportant in criminal casework if close relatives of the suspect, and
      in particular full-sibs, were excluded as possible culprits. In the absence of
      such exclusions the current practice of effectively ignoring such relatives in
      presenting match probabilities could be extremely prejudicial to a suspect, even
      in cases in which there is no direct evidence to incriminate his/her relatives.

PMID- 7649756
TI  - Morphological variation in a natural population of Drosophila mediopunctata:
      altitudinal cline, temporal changes and influence of chromosome inversions.
AB  - To characterize the morphological variation in a natural population of Drosophila
      mediopunctata, males were collected on three occasions at a single locality. From
      each wild-caught male 14 body measures were taken and the karyotype for
      inversions on chromosomes X and II was determined. Through a principal components
      analysis, two sources of variation, identified as size and shape, accounted for
      approximately 80 and 6 per cent of the total morphological variability,
      respectively. The shape component was determined primarily by variations in the
      position of the wing second longitudinal vein. Differences between collections
      were detected both for size and shape. An altitudinal cline was observed in
      respect of wing shape, although altitude explained only a small part of the shape
      variation. Size and shape were affected by chromosome II inversions. However, in
      respect of size, no direct differences were detected between karyotypes but a
      significant interaction between collecting date and karyotype was found. This
      suggests that karyotypes might differ in their norms of reaction in the field.

PMID- 7649757
TI  - The speed of write in nursing: an X ray of hope?

PMID- 7649758
TI  - Competence-building in adolescents, Part I: A self-help nursing intervention.
AB  - The purpose of this study was to test the effects of a self-help nursing
      intervention on adolescent psychosocial competence. A community sample of 139
      adolescents was assigned to three conditions (intervention, delayed intervention,
      and control) within a pretest-posttest design. The self-help nursing intervention
      was a 9-page, 14-step self-help workbook for use by adolescents in dealing with
      upsetting situations in day-to-day living. After a self-assessment of coping,
      subsequent workbook steps aided adolescents in developing alternate coping
      responses and generating other ways to deal with the upsetting situation.
      Adolescents in the three conditions did not differ on pretest measures of
      psychosocial competence: problem-solving appraisal, adolescent self-perception,
      and general self-efficacy. After statistically controlling for pretest scores,
      gender, and age, the intervention group showed more favorable self-perceptions in
      scholastic competence, social acceptance, and conduct/morality compared with the
      control group. However, expected differences in the delayed intervention group
      failed to appear. Thus, anticipated benefits in psychosocial competence were
      found inconsistently. Although not predicted, significant reductions in the
      prevalence of negative affect occurred among adolescents in both intervention
      groups. Overall, the self-help format for delivering psychosocial competence
      training lacked the power needed to bring about consistent benefits for
      adolescents. Testing the self-help workbook in a group context is recommended in
      future nursing intervention research.

PMID- 7649759
TI  - Competence-building in adolescents, Part II: Community intervention for survivors
      of peer suicide.
AB  - Nurses often encounter situations in which they are called upon to assist in post
      suicide community interventions with teachers, church youth group leaders, and
      mental health professionals. Controlled studies of interventions to aid
      adolescents coping with the loss of a peer are lacking. The purpose of this
      study, conditioned by an unanticipated suicide in an ongoing research study, was
      to document changes in psychosocial competence of adolescent peer suicide
      survivors. Following a supportive community intervention, the peer survivor group
      was compared with a similar group of adolescents who did not experience peer
      suicide. Both groups were in the control condition of a larger nursing study of
      social competence-building. The survivor group had significantly greater self
      efficacy immediately after the community intervention and 2 months later when
      contrasted with the comparison group. In addition, the survivor group reported
      greater social acceptance and job competence immediately after the community
      intervention. Correlated t-tests showed the survivor group had significant gains
      in problem-solving appraisal and global self-worth after the community
      intervention, but significant declines in global self-worth and scholastic
      competence 2 months after the intervention. The findings support the belief that
      community interventions are initially worthwhile in helping adolescents to cope
      with peer suicide, but continued supportive intervention may be needed to offset
      declines noted over time in areas such as self-worth and academics.

PMID- 7649760
TI  - Creating a safe passage: the meaning of engagement for nurses caring for children
      and their families.
AB  - The purpose of this study was to uncover the meaning of engagement for nurses who
      care for children and their families. This study employed a hermeneutic
      phenomenological methodology as specified by van Manen (1984, 1990) and Ray
      (1991). A convenience sample consisted of eight nurses who worked in a pediatric
      ambulatory care setting. Data were generated from audiotaped interviews and
      journaling. The first level of reflection revealed the themes and metathemes of
      the meaning of engagement: Making Connection: Becoming Aware of the Person;
      Perceiving the Other: Developing and Nurturing the Relationship; A Sense of
      Investment: Unfolding From Commitment; and Remaining Distant: Choosing Not To
      Engage. In the second level of reflection selected literature further illuminated
      the meaning of engagement. Through deeper reflection, the metaphor Creating a
      Safe Passage surfaced to capture the meaning of engagement. This research
      supports the transformation of health care delivery toward a greater emphasis on
      the caring relationship. Findings illuminate specific characteristics of an
      engaged relationship. Implications for sensitizing health care professionals in
      practice, education, and research are described.

PMID- 7649761
TI  - Perceptions and concerns of the school-age siblings of children with
      myelomeningocele.
AB  - Chronic illness affects all members of the family, including siblings. Siblings
      of children with myelomeningocele have been studied infrequently. This
      descriptive study examined the perceptions and concerns of the school-age
      siblings of children with myelomeningocele and compared sibling responses with
      maternal perceptions of the sibling relationship. The effects of age, birth
      order, and gender were also examined. Fifteen children and their mothers
      participated in the study. Data were collected through a sibling interview and
      maternal survey. Qualitative analysis of the sibling responses revealed a high
      level of empathy and concern for their brothers and sisters with
      myelomeningocele. Maternal responses yielded similar findings. No statement could
      be made regarding the effects of age, birth order, or gender upon the sibling
      relationship. Nurses are in a unique position to assess the perceptions and
      concerns of siblings, and to intervene to ensure that their needs are met and
      their contributions to family life recognized.

PMID- 7649762
TI  - Health problems of sheltered homeless children using mobile health services.
AB  - Homeless families are an increasing problem in the United States, with children
      representing 34% of the total homeless population. This retrospective study
      describes the demographic characteristics and health care problems and concerns
      of sheltered homeless children who used the services of a mobile health van over
      a 1-year period in a midwestern metropolitan area. The patterns of utilization,
      medications prescribed, and referrals are also described. Medical records of 175
      sheltered homeless children who sought care from a mobile health van were
      reviewed. Forty-eight percent of the children were female; 52% were male. The
      majority were under 6 years of age (15% infants, 22% toddlers, 22% preschoolers,
      23% school-age children, and 18% adolescents). The major reasons for seeking
      health care, the primary diagnoses, and treatments are presented. Recommendations
      for using a mobile van to provide efficient, quality health care for this
      population are discussed.

PMID- 7649763
TI  - Supports Animal Drug Availability Act.

PMID- 7649764
TI  - What is your diagnosis? Biaxial fractures of the distal portion of the second and
      fourth metatarsal bones.

PMID- 7649765
TI  - What is your neurologic diagnosis? Intradural-extramedullary malignant sarcoma at
      C1-2 vertebrae in a dog.

PMID- 7649766
TI  - Hypergammaglobulinemia in a dog.

PMID- 7649767
TI  - Nutritional epidemiology in small animal practice.

PMID- 7649768
TI  - Marketing by the veterinarian--some legal considerations.

PMID- 7649769
TI  - Evaluation of a commercially available prothrombin time assay kit for use in dogs
      and cats.
AB  - A commercially available assay kit provided a rapid, inexpensive means of
      evaluating prothrombin time, requiring only 1 drop of fresh blood. We evaluated
      the assay kit for its ability to accurately measure prothrombin time in dogs and
      cats, comparing it with a validated prothrombin time assay performed in
      laboratories. Prothrombin times determined by validated laboratory and assay kit
      methods were compared, using simple regression analysis. Correlations were high
      (canine study, r2 = 0.96; feline study, r2 = 0.90; P = 0.0001 in both studies).
      We concluded that the assay kit compared favorably with the validated laboratory
      technique. The simplicity and speed with which the test can be performed,
      accuracy of results, small blood volume required, and cost-effectiveness make the
      assay kit well suited for prothrombin time measurement by small animal
      practitioners.

PMID- 7649770
TI  - Partial scapulectomy for management of sarcomas in three dogs and two cats.
AB  - Three dogs and 2 cats were treated by partial scapulectomy for management of
      sarcomas of the proximal aspect of the scapula. Surgical margins were considered
      complete in all cases. In 3 animals, limb function was excellent for 8, 18, and
      24 months, respectively, after surgery. Poor limb function persisted in 1 dog
      that developed local metastatic disease to the affected forelimb. One dog had
      good limb function for 3 months after surgery and underwent force-plate analysis,
      which determined a reduction in peak vertical force, decelerating force, and
      stride time for the affected limb, compared with that for the forelimb that was
      not subjected to surgery. Tumor recurrence associated with fibrosarcomas was
      detected in 2 animals. In selected cases, partial scapulectomy can preserve limb
      function and may be considered a viable alternative to limb amputation.

PMID- 7649771
TI  - Intraoperative monitoring of intracranial pressure in five dogs with space
      occupying intracranial lesions.
AB  - Five dogs with space-occupying intracranial lesions underwent lateral
      craniectomy. Brain tissue pressures, reflective of intracranial pressure, were
      monitored during the surgical procedure, using a fiberoptic intracranial pressure
      monitoring system. The intracranial pressure monitoring cable was placed
      superficially in brain parenchyma on the side contralateral to the primary
      lesion. Recordings were made continually throughout the surgical procedure. Each
      dog was treated preoperatively with mannitol, which caused a decrease in
      intracranial pressure prior to craniectomy in only those dogs that initially had
      high intracranial pressure. Complications associated with use of the fiberoptic
      intracranial monitoring system were not evident. Although absolute values for
      pressure varied, pressure trends were helpful in determining effects of surgical
      manipulations on intracranial pressure in these dogs.

PMID- 7649772
TI  - Dry extracorporeal shock wave lithotripsy for treatment of ureterolithiasis and
      nephrolithiasis in a dog.
AB  - A second-generation lithotriptor was used to perform dry extracorporeal shock
      wave lithotripsy in a dog with ureterolithiasis, nephrolithiasis, and chronic
      renal failure. Previous studies on the use of lithotripsy in dogs have involved
      first-generation machines and have primarily concentrated on acute and chronic
      effects of lithotripsy in experimental models. Treatment in this dog resulted in
      resolution of ureteral obstruction, ureterolithiasis, and nephrolithiasis, and
      avoided complications associated with ureteral and renal surgery. The only
      complication was substantial hematuria of 12 hours' duration immediately after
      the procedure. Second-generation lithotripsy may offer an effective treatment for
      ureterolithiasis or nephrolithiasis in selected dogs.

PMID- 7649773
TI  - Treatment of nephroblastoma in a juvenile dog.
AB  - A 4-month-old female Bernese Mountain Dog that was examined because of abdominal
      distention was found to have a nephroblastoma during exploratory laparotomy.
      Nephrectomy was performed, but the tumor could not be completely resected. A
      chemotherapeutic plan for this dog was created by adapting current
      recommendations for treatment of people with nephroblastoma. Chemotherapy was
      tolerated extremely well; however, tumor progression became evident after 15
      weeks of treatment, and the dog was euthanatized. Widespread metastasis was found
      at necropsy. Little is known about the natural behavior of this tumor in dogs.

PMID- 7649774
TI  - Treatment of cats with ocular disease attributable to herpesvirus infection: 17
      cases (1983-1993).
AB  - Medical records of 17 cats with ocular disease attributable to herpesvirus
      injection were reviewed. Herpesvirus infection was confirmed by a positive result
      on an immunofluorescent antibody test or by detection of dendritic corneal
      ulcers. Cats were 3 months to 23 years old (mean, 4.8 years). Sex or breed
      predilections were not evident. Vaccination history was available for 13 cats, 9
      of which had been adequately vaccinated against feline viral rhinotracheitis,
      calici, and panleukopenia viruses. Six cats had a history of respiratory tract
      disease. Twelve cats were tested for FeLV, and 3 had positive results; 7 cats
      were tested for feline immunodeficiency virus, with 1 positive result. The most
      common ocular abnormality seen was conjunctivitis (13/17 cats), followed by
      dendritic corneal ulcers (10/17 cats). Keratitis was detected in 6 of 17 cats,
      and nondendritic corneal ulcers in 3 of 17 cats. Corneal sequestra were evident
      on initial examination or developed during the follow-up period in 4 of 17 cats.
      Keratoconjunctivitis sicca was diagnosed in 2 of 17 cats, and anterior uveitis
      was evident in 1 of 17 cats. All cats had 2 or more clinical ocular abnormalities
      associated with herpesvirus infection. Treatment with topically applied antiviral
      medications was instituted in 14 cats, including idoxuridine in 7, vidarabine in
      4, and trifluridine in 3. Antibiotics were used topically in 10 cats, and
      atropine was used in 3 cats. Topical administration of corticosteroids was used
      in 2 cats. Recombinant human alpha-interferon was given orally to 3 cats in
      conjunction with topical administration of antiviral agents. In addition to
      medical treatment, 4 cats were treated surgically.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7649775
TI  - Hyperlipidemia, hyperlipemia, and hepatic lipidosis in American miniature horses:
      23 cases (1990-1994).
AB  - The medical records of 23 American Miniature Horses with hyperlipidemia,
      hyperlipemia, or hepatic lipidosis were reviewed. The most common clinical signs
      were anorexia and lethargy. The mean duration of clinical signs was 2.4 days. A
      primary disease was identified in 19 cases. Enterocolitis was the most common
      primary disease (n = 10). Intentional feed restriction, as part of treatment for
      colic, resulted in hyperlipemia in 2 horses and hyperlipidemia in 1. Four horses
      had primary hyperlipemia, 3 of which had signs of hepatoencephalopathy secondary
      to hepatic lipidosis. Dextrose, heparin, and insulin were the most common
      treatments. The overall survival was 61% (14/23). All horses with peak serum
      triglyceride concentrations > 1,200 mg/dl died or were euthanatized, whereas all
      but 1 with peak serum triglyceride concentrations < 1,200 mg/dl survived. These
      findings suggest that when American Miniature Horses, like other ponies and
      donkeys, are in a negative energy balance, they can rapidly develop
      hyperlipidemia or hyperlipemia. Early detection and treatment may improve
      survival.

PMID- 7649776
TI  - Scintigraphy for diagnosis of avulsions of the origin of the suspensory ligament
      in horses: 51 cases (1980-1993).
AB  - The medical records of 34 horses with a diagnosis of avulsion of the origin of
      the suspensory ligament that had been admitted to the veterinary medical teaching
      hospital between 1980 and 1993 were identified. In addition to clinical
      examination, 21 of 34 horses had scintigraphy and radiography performed during
      their examination. The usefulness of scintigraphy and radiography were assessed
      by comparing the initial findings reported in the medical record to those
      obtained in a retrospective review of the images. Thirty other horses with
      scintigraphic lesions of the proximal aspect of the third metacarpal/metatarsal
      bone but with a confirmed diagnosis other than avulsion of the suspensory
      ligament served as controls for lesion specificity. Scintigraphy (bone phase, n =
      21) revealed increased uptake in all horses in both reviews. Only 14 of 21 (67%)
      horses radiographed, however, had at least 1 lesion during the initial
      radiographic evaluation that was reported to be suggestive of avulsion. When the
      radiographs were reviewed retrospectively, the radiologist identified 18 of 21
      (86%) horses with lesions consistent with avulsion. The interpretation of
      scintigraphy appeared to be a more repeatable and sensitive diagnostic method
      than radiography. However, though scintigraphy was sensitive in identifying
      inflammation of the proximal aspect of the metacarpal/metatarsal region, no
      specific diagnosis of avulsion could be made without coincident radiography; the
      specificity of scintigraphy in diagnosing avulsion of the suspensory ligament was
      only 41% (21/51).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7649777
TI  - Effect of transportation on fatal fibrinous pneumonia and shrinkage in calves
      arriving at a large feedlot.
AB  - A retrospective, epidemiologic field study was performed to determine whether
      calves that were transported greater distances from the auction market to the
      feedlot were at significantly higher risk of developing fatal fibrinous pneumonia
      (shipping fever). The study involved all 45,243 springborn steer calves that were
      purchased from auction markets and moved into a large commercial feedlot between
      September 1 and December 31 over a 4-year period (1985-1988). For all 4 years of
      the study, the distance calves were transported from the market to the feedlot
      and their shrinkage or subsequent death loss from fibrinous pneumonia were not
      correlated. The risk of fatal fibrinous pneumonia for calves arriving from nearby
      markets was just as high as that for calves transported much greater distances.
      The results suggested that calves can be purchased from more distant markets
      without having to discount their price for higher expected death losses.
      Differences between short and long hauls explained little, if any, of the
      variation among truckloads of calves in the risk of fatal fibrinous pneumonia.

PMID- 7649778
TI  - Effect of pretransit mixing on fatal fibrinous pneumonia in calves.
AB  - A retrospective, epidemiologic study was performed to quantify the mixing of
      calves from various sources at auction markets, and to determine whether mixing
      at the markets and the risk of fatal fibrinous pneumonia (FFP) at the feedlot
      were associated. In this study, 32,646 spring-born steer calves that entered a
      single large feedlot during the fall seasons between 1985 and 1988 were traced
      back to their originating auction market, and sales tickets were used to measure
      the number of farm sources that contributed to each truckload of calves.
      Individual cow/calf producers contributed a median of only 2 calves/truckload
      arriving at the feedlot in this study. An average truckload of 60 steers
      comprised calves from as many as 20 to 30 farms. The degree of mixing varied
      little over time and could not, therefore, be used to explain the large
      variations in FFP risk during different months and different years of the study.
      However, variation in the degree of mixing of calves from various sources at the
      markets evidently was responsible for differences in FFP risk among truckloads
      assembled by different buyers. When truckloads were grouped by buyer, FFP risk
      and mean number of calves per source were negatively correlated in 1986 (r = 
      0.67, P = 0.099), and in 1987 (r = -0.90, P = 0.002). These variables also were
      negatively correlated in 1988 (r = -0.56), although the correlation was not
      significant. The positive linear relationship between mixing of calves in
      truckloads supplied by different buyers and subsequent FFP risk suggested that
      veterinarians and feedlot owners should more aggressively observe and treat
      calves from truckloads that were highly mixed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7649779
TI  - Feed contamination with Candida krusei as a probable source of mycotic mastitis
      in dairy cows.
AB  - Over 3 months, yeasts were isolated in pure culture from milk samples obtained
      from 8 lactating cows with acute mastitis and from 1 cow with subacute mastitis.
      Eight of the isolates were identified as Candida krusei; 1 isolate was not
      submitted for identification. The affected cows were assigned to separate milking
      groups and had not been treated by intramammary administration of antibiotic
      before the outbreak. Remission of disease without treatment was observed,
      followed by shedding of the yeast in milk for 2 to 5 weeks. Median somatic cell
      counts in the affected cows before, during, and 2 months after the onset of
      clinical signs were 93,000; 1,793,000; and 135,000 cells/ml, respectively. Wheat
      silage was found to be the probable source of the infecting microorganism,
      whereas inadequate milking hygiene resulted in its persistence in the herd.
      Following replacement of the silage and improvement of the milking hygiene, the
      outbreak ceased. Candida krusei thus may cause mastitis in cattle not only
      following intramammary antibiotic treatment, but also in conditions of heavy
      environmental contamination, in conjunction with inadequate milking hygiene.

PMID- 7649780
TI  - Aneurysm of the cranial mesenteric artery in a cow.
AB  - Exploratory laparotomy of an adult dairy cow, examined because of acute signs of
      persistent abdominal pain, revealed a firm pulsatile mass with associated
      fremitus just distal to the origin of the cranial mesenteric artery. The cow died
      acutely 2.5 days after surgery. A dilated, thin-walled, sacculated aneurysm,
      which had ruptured, was located along the proximal portion of the cranial
      mesenteric artery. It was postulated that the aneurysm developed secondary to
      structural defects in the arterial wall, but caused no clinical signs until
      enlargement and local tissue stretching or circulatory disturbances caused
      intestinal ischemia, resulting in abdominal pain. Aneurysms of visceral arteries
      in cattle should be considered as another differential diagnosis for signs of
      abdominal pain after more common causes such as severe bloat, mesenteric root
      volvulus, intussusception, cecal dilatation/volvulus, and uterine torsion have
      been excluded.

PMID- 7649781
TI  - A cluster analysis of the neurons of the rat interpeduncular nucleus.
AB  - The morphometric characteristics of the neurons of the interpeduncular nucleus
      (IPN) in the rat were investigated by cluster analysis in order to identify
      neuronal groups which are morphometrically homogeneous, and to define their
      position and density in the IPN subnuclei. Two clusters of cells were detected.
      Cluster 1 neurons had a larger perikaryal size with a mean cross-sectional area
      of 170 microns2 and a high nuclear/cytoplasmic ratio. They were located mainly in
      the pars dorsalis (37%) and pars medialis (34%) rather than in the pars lateralis
      (29%). Cluster 1 neurons were also more frequent at the rostral (31%) and caudal
      (57%) poles than in the central part of the IPN. Cluster 2 cells showed a smaller
      mean perikaryal area (110 microns2), a small nucleus and abundant cytoplasm. They
      were equally distributed throughout the whole IPN. These findings suggest the
      existence of a magnocellular region at the rostral pole of the IPN which has not
      been described previously. The presence of IPN regions endowed with specific
      cytoarchitectural characteristics is discussed with respect to the complex
      neurochemical organisation of the nucleus.

PMID- 7649782
TI  - Pancreatic duct inflammatory infiltration in the nonobese diabetic (NOD) mouse.
AB  - The pancreatic duct system during the early stages of type 1 diabetes was
      examined in 8-wk-old female nonobese diabetic (NOD) mice. Infiltration was seen
      to involve the smaller ducts while the larger ducts were usually free from
      ductulitis. The infiltration affected ducts both close to and remote from the
      islets of Langerhans. In the former situation, infiltration of the islet and that
      of the duct were not separable. A strong positivity for both Ia and ICAM-1
      molecules was observed in all infiltrated ducts, indicating that this
      infiltrating process is due to the same elements as are involved in the islet
      inflammation and that also mononuclear cells infiltrating the nonislet ducts
      express adhesive mechanisms. At the ultrastructural level, endocrine cells that
      were mainly of the 'closed' type were observed intermingled with the ductular
      epithelial cells and infiltrating mononuclear cells were detected either in the
      connective layer or among the epithelial cells of the affected ducts.

PMID- 7649783
TI  - Experimental modulation of the reactivity of pleural milky spots (Kampmeier's
      foci) by Freund's adjuvants, betamethasone and mycobacterial infection.
AB  - We studied the response of milky spots in the parietal pleura of the rat and
      mouse to intrapleural instillation of immunomodulatory agents such as complete or
      incomplete Freund's adjuvants and betamethasone, and also to infection by
      mycobacteria (M. avium). Both incomplete (mineral oil) and complete (mineral oil
      plus dead mycobacteria) adjuvants, as well as M. avium infection, induced a
      striking increase in the size and cellularity of the pleural milky spots whereas
      betamethasone caused a slight atrophy. The extensive inflammatory infiltrates
      observed after adjuvant injection differed between milky spots reactive to
      complete and incomplete Freund's adjuvants. Fifteen days after adjuvant
      administration, the pleural milky spots of rats were still enlarged and
      hypercellular but differences were noted in the size of milky spots of the pleura
      between the 2 adjuvant treatments: animals submitted to injection of complete
      Freund's adjuvant showed an increase in the size of milky spots from d 3 to d 15,
      while the size of milky spots of the incomplete Freund's adjuvant treated group
      showed a decrease in size from d 3 to d 15. The milky spots at d 15 were well
      organised: reticulin fibres permeated the whole area of the milky spot and the
      different cell types were evenly distributed. Histiocytes, which were previously
      confined to the inner layer, were now the main cell type in all areas of milky
      spots. A moderate number of mast cells and a few eosinophils were also seen.
      Complete Freund's adjuvant caused the formation of granulomas in the milky spots,
      a change that was not detected in animals treated with incomplete
      adjuvant.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7649784
TI  - Anatomy of adult female common marmoset (Callithrix jacchus) reproductive system.
AB  - Better appreciation of the female reproductive anatomy of the common marmoset
      (Callithrix jacchus) should improve the prospects for nonsurgical embryo transfer
      in this model. Vaginal measurements were performed in 8 female adult marmoset
      monkeys. Four monkeys were measured at laparotomy for gross internal anatomy, and
      1 monkey was analysed at autopsy. The vagina of the marmoset monkey was found to
      be divided into a lower and upper vagina with a marked vaginal isthmus between
      them. The mean lengths of the lower and upper vagina were 17 mm (34 mm in total
      vagina). The mean uterine size was 8.4 (length) x 10.0 (width) x 6.4 (thickness)
      mm, with the ovary measuring 5.3 x 4.3 x 3.8 mm. The mean length of the fallopian
      tube was 10.5 mm with a width of 1.5 mm. Nonsurgical embryo transfer in this
      model appears to be feasible, but the proportionally long vagina and short
      uterine cavity needs to be recognised.

PMID- 7649785
TI  - Perikaryal projections of spinal ganglion neurons: quantitative differences
      between membrane domains in contact with different microenvironments.
AB  - The perikarya of spinal ganglion neurons display numerous slender projections. In
      the present investigation we have studied whether the extent of these projections
      is uniform over the entire perikaryal surface or whether there is a difference
      between the regions of the perikaryon in contact with different
      microenvironments. In spinal ganglia of the rat and the lizard we have analysed
      about 200 neuronal cell bodies arranged in pairs and have compared the extent of
      the projections quantitatively in the areas of interneuronal contact with that in
      the areas of neuron-to-satellite cell contact. In both species we have found that
      the projections are present over the entire perikaryal surface and that the
      overall development of the perikaryal projections is significantly greater in
      those portions of the surface in contact with satellite cells than in the
      portions in contact with another neuron. On the basis of these observations we
      conclude that the outgrowth of perikaryal projections is an intrinsic property of
      the nerve cell body which is manifested over the entire perikaryal surface; there
      is, however, an extrinsic influence from the microenvironment of the neuron,
      which may account for the quantitative differences in different domains of the
      perikaryal surface.

PMID- 7649786
TI  - Spermatogenesis and ultrastructure of a peculiar acrosomal formation in the musk
      shrew, Suncus murinus.
AB  - Spermatogenesis and acrosomal formation in the musk shrew, Suncus murinus, were
      studied by light and transmission electron microscopy. The cycle of the
      seminiferous epithelium was divided into 13 stages based on the characteristics
      of acrosomal change and nuclear shape, appearance of meiotic figures, location of
      spermatids, and period of spermiation. The relative frequencies of stages 1 to 13
      were 5.1, 5.9, 10.1, 8.8, 12.5, 11.5, 10.6, 7.9, 6.0, 4.8, 8.9, 3.1 and 4.8,
      respectively. Additionally, spermatid development was subdivided into 13 steps.
      Acrosomal formation during spermiogenesis in the musk shrew was quite
      characteristic. However, in contrast to other mammalian species, the nucleus
      remained in the middle region of the seminiferous epithelium, and only the
      acrosome extended towards the basement membrane, beginning at step 7. The
      extension of the acrosome was conspicuous and reached maximum at step 9. At that
      time, the tip of the acrosome extended nearly to the basement. The acrosome of
      maturing spermatids was about 3-fold longer than that of spermatozoa. Thereafter,
      the acrosome gradually shortened and became flat. The enormous fan-shaped
      acrosome was completely formed at step 13. The prominent extension and subsequent
      shortening and flattening of the acrosome in the musk shrew appears to be a
      unique process to form the enormous fan-shaped acrosome.

PMID- 7649787
TI  - Ultrastructural study of the Merkel cell and its expression of met-enkephalin
      immunoreactivity during fetal and postnatal development in mice.
AB  - The morphological changes and the expression of met-enkephalin immunoreactivity
      of Merkel cells during fetal and postnatal development were investigated in touch
      domes and sinus hair follicles of mice by transmission electron microscopy. In
      prenatal fetal mice, the Merkel cells were mainly oval in shape and had slightly
      lobulated nuclei. These fetal Merkel cells (14, 16, 18 d gestation) which were
      not innervated showed a large number of accumulated dense-core granules in their
      cytoplasm as compared with the innervated Merkel cells which appeared in adult
      mice. No Merkel cells could be found in d 10 and d 12 fetuses. Innervation of
      Merkel cells was found to increase with age. The location of Merkel cells in
      juvenile, adult and even old mice was very similar, cells being found mainly in
      the basal layer of the epithelium. Using the electron-microscopic immunogold
      method, met-enkephalin-like substance was consistently located in the dense-core
      granule region of both innervated and noninnervated Merkel cells throughout the
      whole developmental stage. Interestingly, it was also found that the labelling
      intensity of met-enkephalin immunoreactivity was significantly higher in Merkel
      cells of younger age groups than in adult and old age groups. None of the nerve
      terminals associated with Merkel cells were labelled. The present study supports
      the theory of an epidermal origin of Merkel cells followed by the trophic growth
      of nerve fibers induced by the peptides.

PMID- 7649788
TI  - Ultrastructure of blood vessels in the head kidney of the carp, Cyprinus carpio.
AB  - The ultrastructural features of blood vessels were examined by transmission and
      scanning electron microscopy in the perfused and nonperfused head kidney of the
      carp. They consisted mainly of the sinusoidal capillaries, arterioles, veins and
      portal veins. The sinusoidal capillaries were composed of endothelial cells that
      frequently exhibited large pores and an indistinct basal lamina. Some endothelial
      cells were trabecular in shape and protruded into the lumen. The reticular cells
      frequently attached to the outside of the endothelial cells, and macrophages were
      located on the luminal and abluminal surfaces of the endothelial cells. The
      arterioles possessed continuous endothelial cells with a thick basal lamina,
      continuous smooth muscle layers and a thick adventitia with collagen fibres and
      reticular cells. The veins were characterised by fenestrated endothelial cells
      and thin connective tissue. The portal veins were composed of continuous electron
      lucent endothelial cells and thick layers of reticular cells and collagen fibres.
      The differences between the endothelial cells in each blood vessel probably
      reflect the various functions of the carp head kidney. The ultrastructural
      features of the sinusoids and the portal veins resemble those of lymphatic
      vessels of mammals and appear to relate to macrophage and lymphoid cell migration
      and proliferation in the carp head kidney.

PMID- 7649789
TI  - A bromodeoxyuridine labelling study of proliferating cells in the brainstem
      following hypoglossal nerve transection.
AB  - The proliferative activity in the hypoglossal nucleus following hypoglossal nerve
      injury has been studied with the 3H-thymidine analogue, bromodeoxyuridine
      (BrdUrd). BrdUrd was injected into cisterna magna of the rat brain 2 h prior to
      killing and subsequently visualised with immunofluorescence. The peak of BrdUrd
      labelling in the hypoglossal nucleus occurred at 2 d following nerve transection
      and a lower level at 4 and 7 d postoperatively. BrdUrd labelled cells were also
      found outside the anatomical boundaries of the hypoglossal nucleus, conceivably
      mainly corresponding to the dendritic extension of the axotomised neurons. It is
      therefore concluded that microglial cells are activated in relation to the entire
      intramedullary portion of the axotomised neurons and not only in the immediate
      vicinity of the perikarya. Double labelling experiments with specific markers for
      astrocytes, oligodendrocytes and microglial cells showed that only microglial
      cells were BrdUrd positive at all postoperative survival times examined. It is
      therefore concluded that microglial cells are the only glial cell type which
      proliferate in the hypoglossal nucleus following peripheral nerve injury.

PMID- 7649790
TI  - Hepatocyte growth factor (HGF/SF) is expressed in human epithelial cells during
      embryonic development; studies by in situ hybridisation and northern blot
      analysis.
AB  - This study reports the tissue distribution of Hepatocyte Growth Factor-Scatter
      Factor (HGF/SF) in human fetal tissue using Northern analysis and in situ
      hybridisation techniques. In tissue from fetuses of 9-17 wk gestational age, the
      6 kb mRNA transcript for HGF/SF was demonstrated in many tissues but prominently
      in liver, intestine, gall bladder and spleen. In situ hybridisation demonstrated
      that HGF/SF expression was not confined to mesenchymal tissues, as suggested by
      previous studies but was expressed in epithelial tissues, particularly in small
      intestine, keratinising epithelium of tongue, skin and oesophagus. In the small
      intestine epithelial expression was strikingly regional, being confined to the
      crypt region, the site of enterocyte proliferation. Northern analysis of tissues
      for c-met mRNA, representing expression of the HGF/SF receptor, demonstrated
      receptor expression in all tissues studied except the thyroid gland.

PMID- 7649791
TI  - Innervation of the tylotrich-touch dome complexes in rat skin: changing patterns
      during postnatal development.
AB  - The tylotrich-touch dome complexes of the rat were studied in detail at thoracic
      level, with two objectives: to follow the pattern of innervation of the
      individual complexes from birth to maturity and to determine the extent of
      overlap of the segmental nerves supplying them. Techniques included light and
      electron microscopy and histological observations following section of
      intercostal nerves. The touch domes were nearly always supplied from a single
      stem axon; as expected, their terminals increased in number in association with
      the differentiation of target Merkel cells from the epidermis. In general, they
      were supplied from the nearest segmental nerves. The tylotrich follicles were
      each supplied by several stem fibres. The number of palisade terminals applied to
      the epithelial root sheaths reached a maximum during the 2nd and 3rd postnatal
      weeks and declined during the following 2 wk. This overshoot can be regarded as
      another example of hyperinnervation found in the juvenile peripheral nervous
      system. During the period of decline, the stem fibres extended their territory,
      resulting in considerable overlap of the territories of the segmental nerves. By
      the beginning of the 8th week, overlap was relatively scanty, with an irregular
      distribution.

PMID- 7649792
TI  - An ultrastructural study of the ciliary ganglia of cat and monkey (Macaca
      fascicularis) following section of the short ciliary nerves.
AB  - The ultrastructural changes in the ciliary ganglion of the cat and monkey after
      postganglionic (short ciliary) nerve section are described. They were similar in
      both cat and monkey. The nucleus became irregular with prominent indentations on
      the 3rd day after operation and was peripherally located in the neuron from the
      5th postoperative day; by 1 month postoperatively, however it had reverted to its
      former round or oval shape and became centrally located. In the cytoplasm,
      glycogen-like granules were increased. At 5 d after operation, profiles of
      dilated endoplasmic reticulum (ER) and vacuoles were observed at the periphery of
      some neurons. At 7 d after operation, there was an increase in the number of
      dense bodies in the cytoplasm of the neurons. By 1-3 months after operation, most
      of the neurons appeared normal, but there was an increase of profiles of the
      Golgi apparatus in the perinuclear region. In the cat, there was an increase in
      profiles of glycogen-like granules associated with ER stacks. In the monkey, the
      glycogen-like granules were randomly distributed in the cytoplasm. Dendritic
      profiles with large numbers of mitochondria and glycogen-like granules were
      observed as early as the 1st postoperative day and were increased on the 3rd
      postoperative day. Some of the profiles were contacted synaptically by axon
      terminals. Such profiles measured between 0.8 to 4.5 microns in the cat and 1.1
      7.0 microns in the monkey. The number of mitochondria per dendritic profile in
      cross section varied from 8 to 155 in the cat and 28 to 230 in the monkey.
      Dilated and almost empty mitochondria and dense bodies were encountered in such
      profiles. Dendritic profiles packed with mitochondria were still present 1-3
      months after operation, but were reduced in number and dense bodies were only
      occasionally observed. Some of the myelinated and unmyelinated axons underwent
      degeneration, but no ultrastructural change was observed in the axon terminals.
      In some axonal profiles, vesiculotubular structures were also present. At 7-14 d
      after operation, some of the satellite cells became less electron dense. At this
      stage, some of the cells contained phagocytosed electron-dense profiles
      resembling degenerating myelinated axons and cellular debris. Macrophages were
      encountered frequently 3-7 d after operation; some of these were believed to be
      derived from circulating monocytes since they were occasionally observed to
      penetrate the vascular wall. Most of the engulfed material in the cytoplasm of
      the macrophages were myelin-like figures and vesiculated profiles.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7649793
TI  - Age-related changes to the surface ultrastructure of the rabbit temporomandibular
      disc.
AB  - The ultrastructural characteristics of the temporomandibular disc were
      investigated by transmission electron microscopy in rabbits, aged from 7 d to 6
      y. The disc is interposed between the head of the mandibular condyle below, and
      the squamous temporal bone above, within the temporomandibular joint. A single
      layer of flattened mesenchymal cells covered the articular surface of the disc
      during early postnatal development. Gradual disappearance of this cell layer was
      succeeded by the development of an articular surface lamina. The first appearance
      of the lamina coincided with the transition from suckling to adult masticatory
      function. With advancing age, the lamina increased in thickness from 0.3 to 1.0
      micron in adulthood, and was well demarcated from the subsurface tissue. The
      lamina was a continuous, smooth, electron-dense layer, that reacted biochemically
      as proteoglycan complex. The surface lamina may be responsible for the low
      frictional properties associated with articular movement and load, and the
      selective passage of molecules bidirectionally across the cartilage-fluid
      interface. Variations in lamina thickness occurred topographically across the
      disc and were attributed to site concentration of shearing stress. Beneath the
      articular surface lamina were cells surrounded by collagenous intercellular
      stroma. Chondrocytic, fibrocytic and fibrochondrocytic cellular phenotypes were
      present. Subsurface cellular debris accumulated within the rabbit disc from the
      commencement of mastication. Mature adult disc contained expanses of debris,
      attributed to cell death in situ. Foci of mineral precipitates were found within
      ageing discal tissue.

PMID- 7649794
TI  - Perichondrial and endochondral components of mandibular condylar growth:
      morphometric and autoradiographic quantitation in rats.
AB  - In an attempt to determine the contribution of the perichondrial and endochondral
      components to rapid and slow overall condylar growth, mandibular condyles from
      rats aged 21 and 45 d as well as 3 and 6 months were examined by light
      microscopy. A morphometric analysis served to estimate the size of cells and the
      amount of extracellular matrix per cell in the various tissue layers beneath the
      articular surface. Quantitative evaluation of autoradiographic labelling due to
      the presence of [3H]-thymidine, [3H]-proline, and [35S]-sulphate 1.5 or 2 h and 5
      d after injection of the tracer was used to determine the velocity of overall
      condylar growth. A combination of the two types of results allowed the
      calculation of daily rates in (1) the generation of new chondrocytes,
      constituting the perichondrial growth component, and the endochondral components
      comprising (2) net accumulation of extracellular matrix in the cartilage and (3)
      enlargement of the chondrocytes. It was observed that the 3 factors contributed,
      respectively, by about 10-25, 30 and 45-60% to rapid growth and by about 75, 15
      and 10% to slow growth. Thus when growth slowed, the contribution of chondrocyte
      enlargement declined markedly and that of matrix accumulation slightly, while the
      contribution of new cell generation increased correspondingly. Declines in
      chondrocyte enlargement and in accumulation of cartilage matrix that was related
      mainly to decreasing proteoglycan formation were in good agreement with age
      associated variation in weight gain, while peak rates in generation of new
      chondrocytes appeared to be delayed against peak somatic growth. It is concluded
      that (1) endochondral components contribute most to particularly rapid condylar
      growth, exceeding the perichondrial component, and (2) endochondral components of
      condylar growth are regulated by systemic factors that also control somatic
      growth.

PMID- 7649795
TI  - The cytoskeletal framework of chick osteoclasts in resin-less sections.
AB  - The cytoskeletal framework of chick osteoclasts was examined by the resin-less
      polyethylene glycol (PEG) method. Resin-less thin sections revealed changes in
      the 3-dimensional organisation of a microtrabecular lattice during different
      phases of osteoclast activity. This lattice, composed of interconnecting strands,
      occupied part of the osteoclast cytoplasm including the ruffled border and clear
      zone areas. In firmly attached, active osteoclasts, the clear zone exhibited a
      compact and orderly array with a meshwork appearance. This organelle-free area
      could be clearly distinguished from other cytoplasmic regions by the compactness
      of its lattice structure. Well developed membrane infoldings of the ruffled
      border next to the resorption lacunae were composed of interconnected strands,
      some of which were in direct contact with the ruffled border membrane. Migrating
      osteoclasts remote from the bone surface lacked these membrane modifications.
      Their peripheral cytoplasm exhibited a disorganised meshwork of strands without
      the clear zone. While migrating, osteoclasts which still adhered to the bone
      surface, appeared to form loci within the compact lattice structure referred to
      as podosomes. These results demonstrate the dynamic morphological changes in the
      organisation of the trabecular lattice that occur within attached and migrating
      osteoclasts.

PMID- 7649796
TI  - Increase in immunoreactivity to endothelin-1 in the mucosal vasculature and
      epithelium of the large intestine during chronic hypoxia.
AB  - Endothelin-1 is thought to play a role in the regulation of gastrointestinal
      function including its secretory role. This study investigated the localisation
      of endothelin-1 in the mucosa of the large intestine of normoxic and chronically
      hypoxic rats. Chronic hypoxia was produced by maintaining the animals in a
      hypoxic chamber. After animal perfusion/fixation, colonic segments from normoxic
      and hypoxic rats were investigated by the postembedding immunogold labelling
      procedure. In the microvasculature from normoxic (control) animals
      immunolabelling visualised as single particles was low and confined to the
      cytoplasm of endothelial cells. In the epithelium, immunolabelling was found
      mainly at the basal and apical regions of the cells. Chronic hypoxia for 10 d
      greatly enhanced the level of immunolabelling both in endothelial and epithelial
      cells of the mucosa. In endothelial cells clusters of gold particles were found
      in the cytoplasmic matrix and the subendothelium. Epithelial cells showed intense
      labelling, located mainly in the luminal/apical region within vacuole-like spaces
      and in the brush-border. In conclusion, hypoxia induces increase in
      immunoreactivity to endothelin-1 in gut endothelial and especially epithelial
      cells in the colonic mucosa.

PMID- 7649797
TI  - The noradrenergic innervation of the rat thymus during pregnancy and in the post
      partum period.
AB  - The noradrenergic innervation of the rat thymus during pregnancy and the post
      partum period was examined by a sucrose glyoxylic acid method for catecholamines,
      and by high pressure liquid chromatography. Fluorescent nerves decreased in
      number throughout pregnancy when there was an overall loss in thymic weight due
      to cortical involution. These changes are maximal by parturition. There was a
      dramatic increase in nerves between d 21 of pregnancy and d 1 after parturition,
      especially in the capsule and around blood vessels in the connective tissue
      septa. The neonates were removed at parturition and thymic weight was rapidly
      regained. The increased numbers of nerves remained throughout this post partum
      period. Noradrenaline levels in the thymus altered in a similar pattern
      throughout pregnancy and the post partum period, but did not parallel thymic
      weight changes. The mean noradrenaline concentration in the virgin thymus was
      1063 +/- 107 pg/mg protein. Levels remained similar during early pregnancy and
      increased significantly at d 16. Virgin levels were regained by d 21. Values
      peaked after parturition but rapidly decreased over the next 3 days, and remained
      at or below virgin levels to d 28 except for a transient rise at d 10 post
      partum. Adrenaline values were consistently below detection levels. This study
      shows that there are variations in both nerves visualised, and in
      neurotransmitter (noradrenaline) content in the thymus during the course of
      pregnancy and the post partum period. Thus thymic function could be influenced by
      central events (levels of catecholamines in peripheral blood) as well as local
      events mediated by transmitter changes in nerves.

PMID- 7649798
TI  - Morphometric study of the optic nerve of adult normal mice and mice heterozygous
      for the Small eye mutation (Sey/+).
AB  - The Small eye (Sey) gene, which has been mapped to chromosome 2 in the mouse, is
      known to cause variable malformations of the eye and nose. The effect of the gene
      in the heterozygous state is mainly on the eye. A combined electron microscopy
      and morphometric analysis of the optic nerve in adult littermates with a normal
      (+/+) and heterozygous mutant (Sey/+) genotype was carried out. The optic nerve
      could be dissected from the posterior pole of the eyeball to the optic chiasma in
      all the mice examined. The results of morphometric analyses carried out in this
      study show that the Sey gene indirectly affects the normal morphogenesis of the
      optic nerve in the heterozygous mutant Sey male mouse to a significant degree
      compared with its male normal littermate. The heterozygous mutant Sey female
      mouse is also affected, but not significantly so when compared with its normal
      female littermate. The mean nerve cross-sectional area and mean nerve fibre
      counts for the Sey strain are lower than those observed in other strains of mice
      that have been studied. The nerve fibre densities and the spectrum of nerve fibre
      sizes encountered are, however, similar to those seen in other strains of mice.
      We believe that the findings indicate that the smaller mean nerve fibre counts
      observed in the heterozygous mutant (Sey/+) mice compared to their normal (+/+)
      siblings is unlikely to have resulted from primary retinal dysgenesis, but is a
      consequence of the reduced size of their neural retina, and total retinal
      ganglion cell population.

PMID- 7649799
TI  - A scanning electron microscope study of the pecten oculi of the black kite
      (Milvus migrans): possible involvement of melanosomes in protecting the pecten
      against damage by ultraviolet light.
AB  - The pecten oculi of the black kite (Milvus migrans), a diurnally active bird of
      prey, has been examined by scanning electron microscopy. In this species the
      pecten consists of 12 highly vascularised pleats, held together apically by a
      heavily pigmented 'bridge' and projects freely into the vitreous body in the
      ventral part of the eye cup. Ascending and descending blood vessels of varying
      calibre, together with a profuse network of capillaries, essentially constitute
      the vascular framework of the pecten. A distinct distribution of melanosomes is
      discernible on the pecten, the concentration being highest at its apical end,
      moderate at the crest of the pleats and least at the basal and lateral margins.
      Overlying and within the vascular network, a close association between blood
      vessels and melanocytes is evident. It is conjectured that such an association
      may have evolved to augment the structural reinforcement of this nutritive organ
      in order to keep it firmly erectile within the gel-like vitreous. Such erectility
      may be an essential prerequisite for its optimal functioning, as well as in its
      overt use as a protective shield against the effects of ultraviolet light, which
      otherwise might lead to damage of the pectineal vessels.

PMID- 7649800
TI  - Regenerative and other responses to injury in the retinal stump of the optic
      nerve in adult albino rats: transection of the intraorbital optic nerve.
AB  - The proximal stump of the optic nerve was examined by electron microscopy from 1
      d to 8 wk (dpo/wpo) after intraorbital transection. At 1 dpo a layer of axonal,
      cytoplasmic and myelin debris approximately 15 microns thick was present at the
      cut end. A zone approximately 25 microns thick of abnormal and partly degenerate
      tissue composed of many swollen axons filled with organelles of predominantly
      abnormal appearance lay between the zone of debris and more proximal levels of
      the optic nerve, which retained a normal appearance. The earliest putative axonal
      sprouts were seen at 1 dpo in this zone. By 2 dpo, bundles of small nonmyelinated
      axons containing microtubules, almost certainly axonal sprouts, had grown out
      from more proximal regions of the proximal stump and extended as far as its cut
      end. By 3 dpo, large numbers of axonal sprouts, as well as large numbers of
      macrophages and newly formed blood vessels, were seen close to the cut end of the
      proximal stump. Glial cells were not seen to accompany these early outgrowing
      bundles of axonal sprouts. By 5 dpo, the number of sprouts and macrophages had
      increased; many bundles of sprouts were now in contact with the surface of
      astrocytes, which were partly covered by basal lamina. At 7 dpo most of the
      macrophages had disappeared from the most distal part of proximal stump and
      bundles of axonal sprouts, associated with astrocytes, which in some cases had
      penetrated and were fasciculating such bundles, were present at the cut end. The
      regenerating axonal sprouts in the scar-like tissue at the distal end of the
      proximal stump of the optic nerve declined in numbers sharply at 2 wpo and only a
      few sprout-like axonal profiles were present by 8 wpo. Thus while ultimately
      abortive the early regenerative response is vigorous and involves the outgrowth
      of a large number of axonal sprouts in the first week after injury.

PMID- 7649801
TI  - The attachments of the rabbit medial meniscus. A morphological investigation
      using image analysis and immunohistochemistry.
AB  - In the search for a suitable experimental model the rabbit has increasingly been
      used for investigations on the meniscus. The present study focused on the
      morphology and innervation of the anterior and posterior medial meniscal
      attachments in adolescent and adult rabbits in comparison with man. Grossly, the
      posterior attachment has a similar anatomical position as in man, but the
      anterior is inserted more anteriorly and more laterally, with a long ligament
      like structure between the osseous insertion and the meniscal horn. As in man,
      the attachment resembles a ligamentous insertion and contains zones of
      uncalcified and calcified fibrocartilage and subchondral bone. The proportion of
      the calcified cartilaginous zone in the attachment increases during maturation as
      in articular cartilage. Nerve fibres were found not only at the horns but also in
      the uncalcified and calcified fibrocartilaginous zones and the underlying bone.
      The differences between rabbit and human menisci should be borne in mind when
      interpreting data from animal experiments.

PMID- 7649802
TI  - Increased lectin binding capacity of trophoblastic cells of late day 5 rat
      blastocysts.
AB  - The binding of lectins to the trophoblast of rat blastocysts has been studied
      using quantitative ultrastructural cytochemistry. Rat blastocysts from early, mid
      and late d 5 of gestation were stained using biotinylated lectins (Phytolacca
      americana [Phy am], fucose binding protein [FBP] and soybean agglutinin [SBA])
      and a sensitive avidin-ferritin cytochemical method. Electron micrographs of
      ferritin particles along the membrane were processed to produce images for which
      grey scale levels could be established and the ferritin particles automatically
      counted. The ferritin:membrane ratio was then calculated. Increased binding with
      Phy am (which detects short chain oligosaccharides) was found after midday of d
      5, i.e. after hatching. Binding of FBP and SBA did not alter during the period
      studied. The increased concentration of oligosaccharides on the blastocyst
      surface membrane after hatching may have important implications for blastocyst
      attachment to the endometrium.

PMID- 7649804
TI  - Proceedings of the Anatomical Society of Southern Africa. Pretoria, 20-23 March
      1994. Abstracts.

PMID- 7649803
TI  - Professor David Bodian, M.D., Ph.D. (15 May 1910-18 September 1992).

PMID- 7649805
TI  - Intrinsic fibre architecture and attachments of the human epiglottis and their
      contributions to the mechanism of deglutition.
AB  - Two mechanisms have been proposed which address the downfolding of the epiglottis
      during swallowing. The passive mechanism (Fink et al. 1979) focuses on passive
      mechanical forces transmitted through the median hyoepiglottic ligament and pre
      epiglottic adipose tissue to the epiglottis. The active mechanism (Ekberg &
      Sigurjonsson, 1982) expands the passive mechanism to include active contributions
      from the aryepiglotticus and thyroepiglotticus muscles. By means of laryngeal
      microdissection and whole mount orcein staining, distinct bands of fascial
      condensations were identified running from the lateral edge of the epiglottis
      just superior to the attachment of the median hyoepiglottic ligament to the hyoid
      bone near the ends of the greater horns. Neither the proposed active nor the
      passive mechanisms address the possible contribution of these paired lateral
      hyoepiglottic ligaments to epiglottic downfolding. Computer image analysis of
      videofluoroscopic examinations of swallowing was then used to assess the dynamic
      movements of the larynx during swallowing. It was observed that the downfolding
      of the epiglottis occurred in the same video frame as initiation of anterior
      displacement of the hyoid bone and thyrohyoid approximation. Based on the
      anatomical and dynamic relationship of the epiglottis to other laryngeal
      structures, we propose that as the larynx elevates and the hyoid bone moves
      anteriorly, these lateral ligaments exert traction preferentially on the upper
      third of the epiglottis to bring it to a position below the horizontal.

PMID- 7649806
TI  - A three-dimensional evaluation of human facial asymmetry.
AB  - Soft-tissue facial asymmetry was studied in a group of 80 young healthy white
      Caucasian adults (40 men, 40 women) with no craniofacial, dental or mandibular
      disorders. For each subject, the 3-dimensional coordinates of 16 standardised
      soft-tissue facial landmarks (trichion, nasion, pronasale, subnasale, B point,
      pogonion, eye lateral canthi, nasal alae, labial commissures, tragi, gonia) were
      measured by infrared photogrammetry by an automated instrument. The form of the
      right and left hemifaces was assessed by calculating all the possible linear
      distances between pairs of landmarks within side. Side differences were tested by
      using euclidean distance matrix analysis. The mean faces of both groups were
      significantly asymmetric, i.e. the 2 sides of face showed significant differences
      in shape, but no differences in size.

PMID- 7649808
TI  - Structure and composition of the outer connective tissue sheaths of peripheral
      nerve.
AB  - A regular pattern of parallel reflections with a periodicity of approximately 39
      microns has been detected on peripheral nerve fascicles. The reflections have
      been found to originate from a layer of wavy epineurial collagen fibrils arranged
      in register around the entire circumference of the fascicle. The waves were
      observed to be disposed in parallel with the plane of the fascicular sheath and
      along its axis. The pattern was observed in cut or relaxed fascicles in situ as
      well as in isolated and split layers of the epineurium. The pattern was not
      observed on nerve fascicles under tension. An additional structural feature
      consisting of longitudinally disposed elastic fibres was also detected among the
      epineurial collagen fibrils. The perineurial collagen associated with sheets of
      cells was found to be disposed in flattened waves as in the inner layer of the
      epineurium. The period of the waves, however, was much shorter, in the range of 6
      9 microns. From the nature of the wavy structure it can be surmised that on
      stretching or contraction the sheath length may change, thus accommodating
      displacement and movement of nerve fibres.

PMID- 7649809
TI  - Muscle differentiation and morphogenesis in the regenerating tail of lizards.
AB  - The differentiation of muscles in the lizards Anolis and Lampropholis with tails
      that had regenerated for 21-50 d was investigated by light and electron
      microscope autoradiography using tritiated thymidine. At the apex of the
      regenerating tail, groups of 4-8 myoblasts of the promuscle aggregates fused to
      produce bundles of myotubes whose multiple labelled and unlabelled nuclei
      appeared to be distributed at random. The formation of the first myotubes and
      their growth is responsible for the formation of the myotome primordia and their
      separation from the intermuscular connective myosepta. More nuclei were added
      with the lengthening of the myotubes--up to 14-18 nuclei in the oldest proximal
      myotubes. At 4-5 h after injection labelled nuclei were found outside the
      myotubes while at 2-6 d after injection many labelled nuclei were observed in the
      myotubes, particularly near the two ends of the myotubular sarcoplasm contacting
      the myoseptum. This change from the initial distribution suggests that the growth
      of the myotubes takes place mostly at their terminals. There is an apparent
      correlation between the number of nuclei and the final length of the myotubes and
      myotome. The insertion of fibres with a similar number of nuclei and lengths into
      the pinnated connective myoseptum of the original musculature, the autotomy
      plane, probably determines the wave-like shape of the muscles within the
      regenerated myotomes.

PMID- 7649807
TI  - Localisation of extracellular matrix components in the embryonic human notochord
      and axial mesenchyme.
AB  - The unsegmented axial mesenchyme is the first anlage of the embryonic vertebral
      column in amniotes. Its development and differentiation are influenced by the
      notochord. The appearance of extracellular matrix (ECM) components which may
      regulate the developmental processes in the human embryonic axial mesenchyme and
      the notochord was studied in 5 human embryos between Carnegie stages 12 and 14
      (4th and early 5th gestational wk) by using Alcian blue histochemistry and
      immunohistochemistry with antibodies against types I and II collagens, the
      proteoglycans aggrecan, biglycan and decorin, the glycoproteins fibronectin,
      laminin and tenascin and the growth factor TGF-beta. The results demonstrate that
      the notochordal sheath contains high amounts of sulphated glycosaminoglycans,
      hyaluronic acid and the glycoproteins fibronectin, laminin and tenascin during
      all developmental stages examined. Additionally type II collagen and the small
      proteoglycan decorin were found. Type I collagen and the small proteoglycan
      biglycan could be detected in notochordal cells. The number of TGF-beta
      immunoreactive notochordal cells increased between stages 12 and 14. The ECM of
      the axial mesenchyme is rich in sulphated glycosaminoglycans, hyaluronic acid,
      fibronectin and tenascin. Strong immunoreactions for collagen type I were found
      only during the early stage 12. The absence of aggrecan and keratan sulphate
      indicates that large aggregating proteoglycan complexes are missing. Epithelial
      mesenchymal interactions which may be influenced by TGF-beta and the ECM
      components demonstrated are discussed.

PMID- 7649810
TI  - Chemotropism in nerve regeneration studied in tissue culture.
AB  - The neurotropic effect of the distal stump of transected sciatic nerve on
      regenerating axons emerging from the proximal stump was investigated in rats by
      the coculture of excised neonatal dorsal root ganglia and segments of degenerated
      and nondegenerated sciatic nerves. In all cultures, neurites from the ganglion
      extended directly towards the degenerated distal stump and not towards the
      undegenerated nerve segment. Analysis of the supernatants of nerve homogenates by
      native polyacrylamide gel electrophoresis demonstrated that 250 and 18 kDa
      proteins were upregulated in the degenerated distal stumps and that 89, 67 and 65
      kDa proteins were expressed by these stumps but not by normal nerve. Placement of
      the individual protein strips, cut from the gels, in dissociated cultures of
      dorsal root ganglion cells showed that the 89 and 18 kDa strips possessed strong
      neurotropic activity. Neurons survived selectively on these strips and outgrowing
      neurites elongated on the strips, parallel to the direction of the band. When
      explanted dorsal root ganglia were cultured along with the strips, outgrowing
      neurites extended selectively towards those containing the 89 and 18 kDa bands.
      It is concluded that these bands contain chemotropic substances, the nature of
      which requires further investigation.

PMID- 7649811
TI  - Transient expression of transferrin receptors and localisation of iron in
      amoeboid microglia in postnatal rats.
AB  - The expression of transferrin receptors marked by the monoclonal antibody OX-26
      and the localisation of iron were studied in amoeboid microglial cells in
      postnatal rats. Transferrin receptors were vigorously expressed in amoeboid
      microglia in rats ranging from 1 to 10 d of age but were undetectable in older
      rats. Thin serial sections showed that the OX-26 positive amoeboid microglial
      cells were also immunoreactive for OX-42 and ED1. Using Perls' medium, this study
      showed the presence of a considerable amount of iron in amoeboid microglial cells
      in 1-10 d rats. Most iron-containing cells were round but their number had
      diminished by 2 and 3 wk of age, when the iron was localised instead in some
      branched cells which were identified as either oligodendrocytes or ramified
      microglia cells. There has been much speculation on the functional significance
      of transferrin receptors on amoeboid microglia in postnatal rats. It is suggested
      that the receptors facilitate the acquisition of iron necessitated for various
      functions of amoeboid microglia in the developing brain. The presence of iron in
      some oligodendrocytes suggests their involvement in mediating iron mobilisation
      and storage. Its localisation in some ramified microglia in older rats indicates
      the possible role of these cells in sequestration and detoxification of iron in
      the central nervous system.

PMID- 7649812
TI  - The distribution of PDGFs and PDGF-receptors during murine secondary palate
      development.
AB  - The distribution of the 2 homodimer isoforms of platelet-derived growth factor
      (PDGF)-AA and -BB, and their receptors (PDGF alpha-receptor and PDGF beta
      receptor) were mapped immunocytochemically during the development of the
      embryonic mouse secondary palate, from embryonic day (E) 12 to E15. The staining
      patterns of PDGF-AA/alpha-receptor and PDGF-BB/beta-receptor are different.
      Generally, the former is present and the latter is sparse/absent during the
      period of palate development. The localisations of PDGF-AA and alpha-receptor are
      more intensive in the epithelia than in the mesenchyme, and change temporally
      during palatal shelf elevation, midline epithelial seam formation and disruption.
      Before the palatal shelf has elevated (E13), PDGF alpha-receptor is present in
      the palatal mesenchyme, nasal and medial edge epithelia (MEE), whilst PDGF-AA
      stains lightly in the palatal epithelia. During palatal midline epithelial seam
      formation and following its degeneration throughout E14, PDGF-AA and PDGF alpha
      receptor were intensively colocalised in the nasal and midline seam epithelia.
      These findings indicate that the interaction between PDGF-AA and its receptor may
      participate in palate development, particularly in regulating palatal midline
      epithelial seam formation and degeneration.

PMID- 7649813
TI  - The timing of ossification of the limb bones, and growth rates of various long
      bones of the fore and hind limbs of the prenatal and early postnatal laboratory
      mouse.
AB  - In order to study the pattern of ossification of the skeletal components of the
      fore and hind limb of the mouse, intact embryos were isolated between days (d) 15
      and 19 of pregnancy (the morning of finding a vaginal plug is termed d 1 of
      pregnancy), and postnatal animals isolated on d 1 (newborns), 7 and 14 after
      birth. The total number of fore and hind limbs studied for each day of pregnancy
      or postnatal day for the bone growth study is given in parentheses: d 15 (2), d
      16, 17, 18 and 19 of pregnancy (5 specimens for each of these days), d 1
      (newborn), wk 1 and 2, postnatal (4 specimens analysed at each of these times),
      since only the right limbs were studied. For the study involving the time of
      first appearance of ossification centres, either the right or the left limb of
      each of these prenatal and postnatal specimens was analysed. All specimens were
      fixed in 80% ethanol, bulk-stained using alizarin and Alcian blue, in order to
      stain ossification centres and cartilage, respectively, and cleared. The limbs
      were then disarticulated from the axial skeleton at the sternoclavicular and
      sacroiliac joints to facilitate (1) the determination of the sequential pattern
      of ossification in the various cartilage primordia analysed, and (2) the analysis
      of the pattern of growth of the humerus, ulna, femur and tibia. The latter values
      were plotted graphically, and the individual growth rate of each of the long
      bones studied was then deduced and also plotted graphically. The findings
      demonstrated that, with the exception of the femur and ulna, all of the long
      bones studied had significantly different growth patterns. The time of appearance
      of the various centres of ossification in the skeletal elements studied proceeded
      in a similar order to that described by previous authors, though there was some
      discrepancy in the exact time of first appearance of certain ossification
      centres. Of particular interest was the somewhat unusual pattern of ossification
      of the first digits of both the fore and hind limb compared with that of the
      other digits. The data presented here provide useful baseline information on the
      normal sequential pattern of ossification in the fore and hind limb, and the
      characteristic growth pattern of the individual long bones of the limbs in this
      species.

PMID- 7649814
TI  - Patterns of lectin binding during mammalian neurogenesis.
AB  - Temporospatial changes in surface carbohydrates of neuroepithelial cells were
      analysed by means of lectin histochemistry in normal mouse embryos subsequent to
      closure of the neural tube. The lectins used were concanavalin A (con A), soybean
      (SBA), Maclura pomifera (MPA), peanut (PNA), wheatgerm (WGA), succinylated
      wheatgerm (sWGA) and Limax flavus (LFA). Although labelling was obtained with all
      of the lectins, the most striking temporospatial differences occurred with con A
      which in the early embryos (9-10 somites) labelled the basal and intercellular
      surfaces, but not the luminal surfaces of the neuroepithelial cells, whereas in
      the older embryos (26-30 somites), con A showed light luminal surface labelling.
      A midventral wedge of cells in the floor of the neural tube in the older embryos
      also exhibited more intense labelling with con A, WGA, and sWGA than with the
      other lectins. In addition, comparisons of lectin localisation were made between
      the closed neural tube in normal embryos and the open neural folds in the loop
      tail (Lp) mutant mouse in which the neural tube fails to close. Although similar
      temporospatial patterns in lectin localisation occurred as in normal embryos, the
      retention of lectin labelling associated with rounded putative neural crest cells
      that remained sequestered in the apices of the open neural folds, along with an
      attenuation of the luminal reaction in the older abnormal embryos, suggest that
      during normal mammalian development closure of the spinal neural folds may be
      important for the timely exit of neural crest cells as well as for eliciting
      changes in the luminal surfaces of the neuroepithelial cells.

PMID- 7649815
TI  - Differential expression of an endothelial barrier antigen between the CNS and the
      PNS.
AB  - A monoclonal antibody to an antigen (EBA) expressed by neural endothelial cells
      (EC) was used to investigate any difference in the distribution of EBA between
      the CNS and PNS. Pre-embedding ultrastructural cytochemistry of rat sciatic and
      optic nerves was undertaken using anti-EBA, detected with a silver-enhanced gold
      conjugated secondary antibody. LM immunocytochemical localisation of EBA was also
      performed using an HRP-conjugated secondary antibody. EC of pial and parenchymal
      optic nerve vessels were strongly immunopositive for EBA. Vessels of the dura
      were negative. At the EM level EBA was observed on the EC luminal surface. In
      contrast, EC of sciatic nerve were either negative or only weakly immunopositive.
      The molecular characteristics and function of EBA are largely unknown. Therefore
      the functional significance of the present findings remains to be determined.

PMID- 7649816
TI  - Does the area of the glenoid cavity of the scapula show sexual dimorphism?
AB  - The area of the glenoid cavity was determined in 214 scapulae (114 male, 100
      female). Mean values of 9.87 cm2 for the males and 7.18 cm2 for the females were
      found. Presentation of the values as a histogram showed a bimodal distribution
      indicating sexual dimorphism, which was confirmed by the Mann-Whitney-Wilcoxon
      test for unconnected samples. The area of the cavity can therefore be used for
      the sexing of a skeleton. With the described method 60% of males but only 36% of
      females can be graded unambiguously.

PMID- 7649817
TI  - Localisation of glycoproteins and glycosaminoglycans during early eye development
      in the macaque.
AB  - The composition of the extracellular matrix (ECM) was examined in the developing
      lens and optic cup (stages 11-16) of the long-tailed monkey (Macaca fascicularis)
      using peroxidase immunocytochemistry. The glycoproteins, fibronectin, laminin,
      and collagen types I and IV, were consistently associated with basement membranes
      (BM) of ocular epithelia at all stages examined. Discontinuity of the optic cup
      BM was observed during the early stages of evagination (stages 11 and 12); the
      even distribution of all 4 components was reestablished by stage 13 when the
      optic vesicle is closely apposed to the thickened lens placode. While fibronectin
      was most predominant in the mesenchymal matrix, all 4 glycoproteins were observed
      to variable degrees in the periocular mesenchyme. Particularly strong
      glycoprotein reactivity was observed in the interspace between the invaginating
      lens vesicle and optic cup whereas no significant reactivity occurred within the
      lens, developing retina or future corneal epithelium. Two glycosaminoglycans,
      hyaluronic acid and chondroitin sulphate, had virtually identical widespread
      staining patterns in all ocular BM and throughout the periocular mesenchyme and
      adjacent epithelial tissues, including the lens and retina. The observed temporal
      and regional staining patterns suggest that these ECM components are
      morphogenetic factors in the macaque eye, facilitating the complex series of
      integrated tissue interactions, movements and shape changes during the earliest
      stages of lens and optic vesicle morphogenesis. The macaque offers a valuable
      model to study these interactions due to the prolonged period of ocular
      development which is morphologically identical to humans.

PMID- 7649818
TI  - Functional anatomy of the head-neck movement system of quadrupedal and bipedal
      mammals.
AB  - This biomechanical investigation quantified the range of motion of the different
      articulations of the head-neck ensemble in man, monkeys, cats, rabbits and guinea
      pigs. Radiography and dissections were used to establish the degrees of freedom
      of the system. The erect posture and rigidity of the cervical spine in mammalian
      vertebrates are possible because the degrees of freedom of the movements of the
      cervical and upper thoracic vertebrae in passive ranges of motion are asymmetric,
      and thus significantly restricted, when judged from the resting position. The
      total range of motion at the atlanto-occipital articulation varies between
      species. It is approximately 90 degrees-105 degrees in the quadrupedal mammals
      tested, and only 11 degrees or 13 degrees, respectively, in humans and monkeys.
      When at rest, bipeds and quadrupeds hold the atlanto-occipital articulation and
      the upper cervical joints (C1/C2, C2/C3) in a flexed attitude. The total range of
      motion at the cervicothoracic junction (C6-T2) is approximately 6 degrees-80
      degrees in all vertebrates investigated (quadrupeds and bipeds). At rest, the
      vertebral articulations that form the cervicothoracic junction are held in their
      extreme extended positions in quadrupeds and monkeys. In man, the vertebrae of
      the lower cervical spine are kept at a midposition between maximal flexion and
      maximal extension. This latter observation may be related to the permanent
      bipedalism of humans. Collectively, our data indicate that biomechanical
      constraints such as bone structures (e.g. specifically shaped articular
      processes) and ligaments may maintain the intrinsic configuration and self
      supporting structure of the cervical spine. Furthermore, the specialised
      structures in the cervical joints allow movements more or less in particular
      planes of space, and thus biomechanical constraints limit the number of possible
      solutions as to how an animal can perform a given orientating head movement.
      Although we have not entirely clarified the functional implications for head
      movement control of the different sagittal-plane ranges of motion in vertebrates,
      we hypothesise that different mechanical requirements relating to the influence
      of gravity have caused the observed differences between the investigated bipedal
      and quadrupedal mammals.

PMID- 7649819
TI  - Natural involution of muscle in the proximal sesamoidean ligament in sheep.
AB  - In sheep, the muscle component of the proximal sesamoidean ligament, which is
      well developed at birth, undergoes a progressive involution postnatally. The
      development of muscle fibres in the proximal sesamoidean ligament was compared
      with masseter and semimembranosus muscles from before birth into adult life,
      using histochemical, immunohistochemical and biochemical methods. Neonatal myosin
      (a marker for developmental immaturity) disappeared earlier, and the adult
      pattern of myosin expression and fibre type composition was reached earlier in
      the proximal sesamoid ligament than masseter and semimembranosus. Proximal
      sesamoid ligament muscle fibres therefore complete normal development, but with a
      faster time course than the other muscles. Invasion of fibrous connective tissue
      between muscle fibres of the proximal sesamoidean ligament adjoining the
      tendinous component (one feature of the involution) was found to begin
      perinatally, eventually resulting in a marked fibrosis and atrophy of peripheral
      fibres. Regeneration of muscle fibres was absent or abortive, even near areas of
      fibre necrosis.

PMID- 7649820
TI  - The effect of suramin on healing adult rodent dermal wounds.
AB  - Scarring, leading to impaired function, growth and appearance, is a major problem
      following many forms of surgery. Fetal wounds, unlike those in the adult, are
      characterised by a reduced growth factor profile and the absence of scar tissue
      (Whitby & Ferguson, 1991 a, b). The antiparasitic drug, suramin (a heparin
      analogue) inhibits binding of various growth factors (e.g. PDGF, bFGF, TGF-beta,
      EGF, IGF-I, IGF-II) to their receptors in vitro. These growth factors play key
      roles in wound healing. We attempted to manipulate experimentally their
      effectiveness in healing adult rat dermal incisional wounds by injecting suramin
      into the wound margins and comparing the resultant healing with an unmanipulated
      control wound in the same animal. Immunohistochemical staining demonstrated that,
      on d 7 and 14 postwounding, the numbers of monocytes/macrophages and blood
      vessels are markedly increased in suramin treated wounds compared with controls.
      Extracellular matrix deposition is lower, although very compact in organisation,
      lacking the usual honeycombed appearance of normal skin. These effects are
      widespread, being present not only in the wound area, but also in the surrounding
      tissue. No difference was detected at 70 d postwounding between the scars of
      suramin-treated and unmanipulated control wounds in the same animals. All such
      effects are increased slightly through the concentration range of 0.04-40 mg/kg
      suramin, with no significant change as concentrations greater than 40 mg/kg are
      applied. This suggests that suramin has marked effects on the early stages of
      wound healing, which plateau at 40 mg/kg concentration, but has no effect on scar
      formation.

PMID- 7649821
TI  - Dual-channel laser scanning microscopy for the identification and quantification
      of proliferating skeletal muscle satellite cells following synergist ablation.
AB  - Proliferating skeletal muscle satellite cells are the source of additional
      myonuclei which allow skeletal muscle to grow and regenerate. Previously,
      proliferating satellite cells were identified in situ by techniques which were
      limited either by tissue processing time or inability to observe complete muscle
      sections, or by errors made in separating these cells from proliferating
      nonmyogenic cells. To overcome these problems a new method has been devised for
      the identification and quantification of proliferating satellite cells in situ by
      light microscopy. The technique involves dual-channel laser scanning imaging of
      whole muscle sections for the localisation of both the muscle fibre basal lamina
      and the cell division marker bromodeoxyuridine. Using this technique satellite
      cell proliferation was quantified in mouse limb muscle following synergist
      ablation. Dual-channel laser scanning microscopy allowed precise localisation of
      proliferating satellite cells in the experimental model and, after 4 d, synergist
      ablation was shown to have produced significant satellite cell proliferation when
      compared with contralateral and sham-operated controls.

PMID- 7649822
TI  - Comparative anatomy of the cardiac foramen ovale in cats (Felidae), dogs
      (Canidae), bears (Ursidae) and hyaenas (Hyaenidae).
AB  - The structure of the foramen ovale from 16 species representing 4 carnivore
      families, the Felidae, Canidae, Ursidae and Hyaenidae, was studied using the
      scanning electron microscope. The Felidae were represented by 9 domestic cat
      fetuses (Felis catus), 2 snow leopard neonates (Uncia uncia), an ocelot neonate
      (Leopardus pardalis), 2 lion neonates (Panthera leo), a panther neonate (Panthera
      pardus) and 3 tigers (Neofelis tigris), comprising 2 fetuses and a neonate. The
      Canidae were represented by a golden jackal neonate (Canis aureus), a newborn
      wolf (Canis lupus), 8 domestic dog fetuses (Canis familiaris), 3 red fox neonates
      (Vulpes vulpes) and a dhole neonate (Cuon alpinus). The Ursidae were represented
      by a brown bear neonate (Ursus arctos), a day-old grizzly bear cub (Ursus arctos
      horribilis), a polar bear neonate (Ursus maritimus), and 2 additional bear
      fetuses (species unknown). The Hyaenidae were represented by a striped hyaena
      neonate (Hyaena hyaena). In each species, the foramen ovale, when viewed from the
      terminal part of the caudal vena cava, had the appearance of a short tunnel. A
      thin fold of tissue, the developed remains of the embryonic septum primum,
      extended from the distal end of the caudal vena cava for a variable distance into
      the lumen of the left atrium and contributed towards the 'tunnel' appearance in
      all specimens. It constituted a large proportion of the tube, and its distal end
      was straight-edged. There was fibrous material underlying the endothelium of the
      flap, the apparent morphology of which suggested that it comprised cardiac
      muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7649823
TI  - Ultrastructural and immunocytochemical evidence for the presence of polarised
      plasma membrane H(+)-ATPase in two specialised cell types in the chick embryo
      chorioallantoic membrane.
AB  - The chick embryo, confined in the eggshell, has to dispose/buffer the acid
      generated by its metabolism, as well as to release calcium from the shell which
      is used for growth. To localise H(+)-ATPase, electron microscope and
      immunocytochemical studies were conducted on chorioallantoic membranes of 15-17 d
      chick embryos. Ultrastructural studies of the villus cavity (VC) cells in the
      chorionic epithelium demonstrated that their apical plasma membrane, juxtaposed
      with the shell membranes, contains microvilli as well as microplicae which
      possess 9-10 nm studs at a density of 16,700 particles/micron2, a characteristic
      feature of the polarised H(+)-ATPase pump. Immunocytochemical staining, using a
      monoclonal antibody to the 31 kDa subunit of H(+)-ATPase, confirmed the presence
      of large amounts of the vacuolar H(+)-ATPase in the VC shells with a distribution
      highly polarised towards the eggshell membranes. Immunoelectron-microscopic
      localisation studies using a rabbit antiserum to whole bovine H(+)-ATPase and
      immunogold technique, confirmed the localisation of H(+)-ATPase at the apical
      microvilli/microplicae as well as in the subapical vesicles. In the allantoic
      epithelium, the presence of mitochondria-rich (MR) cells was confirmed; it was
      shown that these cells extend through the full thickness of this epithelium. The
      MR cells also contained large numbers of 9-10 nm studs, typical of proton
      secreting cells, in their apical plasma membrane. This was confirmed by
      immunocytochemical staining which showed abundant localisation of H(+)-ATPase in
      these cells; this localisation was, however, diffuse rather than apical.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7649824
TI  - Effects of growth hormone on intestinal morphology of genetically dwarf rats.
AB  - Three groups of Lewis rat were studied: dwarf rats, genetically deficient in
      growth hormone; rehabilitated dwarf rats treated with exogenous growth hormone
      (GH); and normal wild-type rats. The small intestine of each animal was removed
      and simple random transverse sections were taken from the proximal and distal
      regions. The profile areas of villi, crypt and muscle were estimated by point
      count analysis and combined with intestinal length measurements to obtain
      absolute volumes. Villus and primary mucosal surface areas were estimated from
      intersection counts and linear measurements were made of epithelial cell height.
      Distally, villous volume and surface area were reduced by 42% and 39%,
      respectively, in the dwarfs compared with controls. These features were
      significantly smaller (P < 0.01) in dwarfs distally than proximally. Crypt volume
      and epithelial cell height were decreased equally in both proximal and distal
      regions of the intestine of dwarf rats. Following GH administration both features
      increased, crypt volume overshooting control values. These results indicate that
      GH deficiency has a subtle effect on intestinal morphology and that the intestine
      is more sensitive distally than proximally. Reconstitution with GH is capable of
      reversing many of these changes.

PMID- 7649825
TI  - Three-dimensional reconstruction of the Meissner corpuscle of man, after silver
      impregnation and immunofluorescence with PGP 9.5 antibodies using confocal
      scanning laser microscopy.
AB  - The 3-dimensional organisation of the neural component of the human Meissner
      corpuscle was studied after silver impregnation and following immunofluorescence
      for protein gene product 9.5 (PGP 9.5) by confocal scanning laser microscopy. The
      morphology of the Meissner corpuscle was found to show consistent differences
      depending on the labelling method used. After silver impregnation by the
      Winkelmann technique the branches of the afferent nerve fibres of the corpuscle
      showed both thin regions and varicose elements, the latter probably corresponding
      to the portions rich in mitochondria observed by transmission electron
      microscopy. The bulkier elements were never more than 5-6 microns in diameter.
      After immunolabelling for PGP 9.5 the nerve fibre branches in the corpuscle
      always presented flattened and discoidal expansions with a diameter of up to 30
      microns. On the basis of what is known as to the mechanism of action of silver
      impregnations it is considered that the black precipitate preferentially labels
      the parts of neurons that are rich in neurofilaments. In any case the precipitate
      is deposited throughout the neuronal cytoplasm except in the mitochondria and the
      nucleus. Accordingly, in the varicosities of the Meissner corpuscles that are
      rich in mitochondria, there is little space for the formation of the precipitate.
      The use of antiserum against PGP 9.5, which labels the larger proteinaceous
      component of the axoplasm, demonstrates the complete architecture of the neural
      component of the Meissner corpuscle, and visualises the discoidal and flattened
      expansions which are absent in the impregnated corpuscles. It is concluded that
      immunostaining provides images of the corpuscles, and of peripheral neural
      structures that are in general closer to reality.

PMID- 7649826
TI  - Morphometry of the primate bony labyrinth: a new method based on high-resolution
      computed tomography.
AB  - A method is described for taking accurate measurements of the bony labyrinth of
      humans and other primates using high-resolution computed tomography (CT). The
      measurements comprise 8 dimensions, 14 orientations and 2 indices of the
      labyrinth, as well as 7 orientations of related structures of the petrous
      pyramid. Comparison of the measurements taken from CT scans with those taken from
      subsequently made casts and cryosections demonstrates that the method is
      sufficiently accurate to permit the morphometric analysis of labyrinthine size
      and shape. Since the CT method is nondestructive, fast and easy to perform, it is
      applicable to large samples and to rare or precious anthropological specimens.

PMID- 7649827
TI  - Light and electron microscope study of splenoportal milky spots in New Zealand
      black mice: comparison between splenoportal milky spots and aberrant spleens.
AB  - The omentum contains peculiar lymphoid tissues termed omental milky spots. In
      mice, similar milky spots (splenoportal milky spots) are present in splenoportal
      fat bands developing along the splenic artery. We found that New Zealand Black
      (NZB) mice, which are known to develop spontaneous autoimmune diseases, have well
      developed splenoportal milky spots. However, little is known about these milky
      spots. Thus we investigated splenoportal fat bands in NZB mice by light and
      electron microscopy. Splenoportal fat bands contained sporadic aberrant spleens
      as well as abundant milky spots. In addition, transitional forms between
      splenoportal milky spots and aberrant spleens, although sporadic, were present in
      the fat bands. Splenoportal milky spots were supplied with offshoots from the
      splenic artery and were composed of abundant lymphocytes with macrophages, plasma
      cells, granulocytes, megakaryocytes and various stromal cells. In addition, they
      showed active neutrophilic myelopoiesis and probable megakaryopoiesis. Aberrant
      spleens were also supplied by branches from the splenic artery. They showed
      active granulopoiesis, megakaryopoiesis, and erythropoiesis. The transitional
      forms resembled splenoportal milky spots in structure, but the former showed
      extramedullary haematopoiesis of three cell lineages. The morphological
      transition from aberrant spleens, via transitional forms, to splenoportal milky
      spots seems to indicate that splenoportal milky spots represent splenoid lymphoid
      tissues.

PMID- 7649828
TI  - Temporal, 3-dimensional, cellular anatomy of corneal wound tissue.
AB  - We have evaluated temporally the 3-dimensional cellular anatomy of corneal wound
      tissue in the rabbit eye using in vivo tandem scanning confocal microscopy. In
      vivo microscopic studies showed that corneal fibroblast migrated into the wound
      as an interconnected cellular meshwork with long, thin, randomly oriented cell
      processes. Interconnection of fibroblasts was further confirmed by localisation
      of monoclonal antibodies to connexin 43 which demonstrated prominent staining of
      putative gap junctions between fibroblasts. Temporal observations indicated that
      the interconnected cells and cellular processes undergo sequential positional
      changes leading to orientation of cells and interconnected cell processes
      parallel to the wound margin. Laser scanning confocal microscopy of en bloc,
      phalloidin-stained corneal wounds showed prominent intracellular f-actin bundles
      (i.e. stress fibres) within cell processes which formed an extensive interwoven
      pattern within the wound.

PMID- 7649829
TI  - Optic nerve hypoplasia in the fetal alcohol syndrome: a mouse model.
AB  - Optic nerve hypoplasia is commonly observed in children affected by the fetal
      alcohol syndrome, and is believed to contribute to their poor visual acuity. We
      have used a 'binge' model of alcohol abuse in an attempt to recreate this
      hypoplasia in a mouse model. Pregnant female (C57BL/6 x CBA)F1 mice were injected
      intraperitoneally with a single dose of a 25% solution of ethanol (v:w), either
      on d 11 or d 12 of gestation. Optic nerves were prepared for transmission
      electron microscopy from offspring at 3, 6, 9 and 15 wk of age (n = 64). A
      systematic random sampling technique was used to analyse both the cross-sectional
      areas of the optic nerves from semithin sections, and the numbers and cross
      sectional areas of myelinated axons from thin sections. We found no significant
      differences either in the cross-sectional area or in the number of axons in the
      optic nerves between 3 and 9 wk from control and alcohol-treated groups. From 9
      to 15 wk, alcohol-treated groups showed a loss of approximately 25% of myelinated
      axons (65,931 +/- 2806-49,186 +/- 3194: mean number of axons +/- S.E.M.,
      respectively). Over the same period the number of axons in control groups was
      relatively stable (62,087 +/- 2043-64,703 +/- 3607). This resulted in an optic
      nerve with statistically significantly fewer myelinated axons at 15 wk in the
      alcohol-treated group, and was reflected in a trend towards a smaller cross
      sectional area of the optic nerve in alcohol-treated groups.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7649831
TI  - Classification of the drainage patterns of the renal veins.
AB  - Variations in the drainage patterns of the renal veins are well described, but
      existing classifications of the renal veins have deficiencies. This study aimed
      to formulate a practical classification of their drainage patterns, taking into
      consideration the number of primary tributaries, additional renal veins and
      variations. The venous system of 306 kidneys (from 131 males and 22 females)
      obtained from 100 pairs of resin casts and 53 pairs of plastinated kidneys were
      analysed. Based on a proposed definition of the renal vein, 3 major types (I, II,
      III) were identified using the drainage pattern of the primary renal vein
      tributaries and the renal vein as a basis on both the left and right sides. Type
      IA occurred most frequently (38.6%) and was commoner on the left. Type IB was the
      second most frequent (25.2%), with the other types showing lower and similar
      frequencies (10.1-14.4%). Statistically significant differences were noted
      between the left and right kidneys with regard to the classification into the
      different types (P < 0.0001). The proposed classification system is practical and
      has surgical and uroradiological relevance.

PMID- 7649830
TI  - Age-related variations in the horizontal and vertical diameters of the pedicles
      of the lumbar spine.
AB  - The horizontal and vertical diameters of the pedicles of the lumbar vertebrae
      were measured from plain anteroposterior radiographs of the lumbar spines of male
      and female subjects aged from 10 to 65 y. The results showed that there were
      significant differences between the pedicle diameters of males and females.
      Horizontal diameters ranged from 7.4 to 13.6 mm in females and from 7.5 to 14.2
      mm in males. Female vertical diameters ranged from 14.2 to 18.2 mm whilst male
      vertical diameters ranged from 14.8 to 20.7 mm. Generally, there was a
      cephalocaudal increase of diameters in both sexes. Significant age-related
      variations of pedicle diameters were noted at all segmental levels. Within the
      adolescent group (10-19.9 y), the diameters of the 10-14.9 y group and 15-19.9 y
      group differed significantly (P < 0.001). When the pedicle diameters of the
      individual age groups were compared, the pedicles of the 10-19.9, 20-29.9, 30
      34.9, 40-49.9, and 50+ y groups were found to be significantly different from
      each other. The evidence suggests that pedicle diameters undergo continuous
      change throughout the age range studied. The changes are characterised by
      increase of diameters in some age groups and decrease in others, but there was an
      overall increase of both vertical and horizontal diameters as the age groups were
      followed from the youngest to the oldest. The pattern of variation with age
      differed for horizontal and vertical diameters. After the 5th decade, female
      horizontal and vertical diameters showed a tendency to increase while male
      diameters decreased.

PMID- 7649832
TI  - Does early monocular enucleation in a marsupial affect the surviving uncrossed
      retinofugal pathway?
AB  - Monocular enucleations have been done during early stages (postnatal days 3 to 9)
      of visual system development of Monodelphis domestica, in order to determine
      whether in this marsupial, as in several eutherian mammals, there are any
      interactions between the pathways from the two eyes in establishing the uncrossed
      retinofugal projection. We have examined the distribution and the number of
      retrogradely labelled ganglion cells that project to the same side of the brain
      from the surviving eyes shortly after the uncrossed pathway is first formed in
      normal development (postnatal days 14 to 28). Even at these early stages of
      development the surviving uncrossed pathway shows no significant reduction,
      confirming earlier observations of adult marsupials and showing that at no stage
      in development is there any evidence that the crossed pathway from one eye
      influences the navigation of axons that will form the uncrossed pathway from the
      other eye. This is in sharp contrast to observations of mice, rats and ferrets
      and is in accord with expectations based on the difference of the chiasmatic
      structure in marsupials as compared with eutherians.

PMID- 7649833
TI  - Morphometric analysis of myelinated fibre composition in the optic nerve of adult
      C57BL and CBA strain mice and (C57BL x CBA) F1 hybrid: a comparison of
      interstrain variation.
AB  - In a study involving 50 optic nerves isolated from 3 different strains of adult
      male mice, C57BL, CBA and (C57BL x CBA) F1 hybrids, and from adult female CBA
      strain mice, we observed that the mouse had a lower mean total myelinated nerve
      fibre count than other mammals such as the rat, cat, rabbit, monkey and man where
      similar information was available from the literature. The nerve fibre spectrum,
      however, which mostly consisted of small diameter fibres, was similar to the
      distribution seen in these other species. The largest myelinated nerve fibres
      observed in any of the strains of mice investigated had a diameter of not more
      than 1.92 microns. The C57BL optic nerve had the largest population of large
      diameter fibres, while the F1 had the largest population of small diameter
      fibres. In all the strains of mice investigated, the distribution of nerve fibres
      was unimodal, with a modal diameter of 0.48 microns. The mean nerve fibre
      diameter was 0.62 +/- 0.02 microns (S.E.M.), 0.57 +/- 0.03 microns and 0.55 +/-
      0.01 microns for C57BL, F1 and CBA, respectively. The F1 had the lowest
      population of fibres around the modal diameter. The myelinated nerve fibres were
      most densely packed in the CBA strain of mice, whereas the C57BL was the least
      densely populated. There was a significant interstrain difference in the
      parameters measured between the 3 strains of mice studied, whereas there was no
      significant intrastrain difference.

PMID- 7649834
TI  - Star volumes of villi and intervillous pores in placentae from low and high
      altitude pregnancies.
AB  - Histological sections of placentae from pregnancies completed at low altitude
      (400 m) and high altitude (3600 m) in Bolivia were analysed using a stereological
      estimator of the star volumes of villous 'domains' and intervillous 'pores'. The
      purpose was to test whether or not differences in the overall volumes of these
      compartments are accompanied by changes in their geometrical relationships.
      Whilst total placental volume did not vary with altitude, the total volume of
      villi declined by about 25% and total intervillous volume increased by 40% at
      high altitude. The star volume of villi also decreased by 25% (from 1.5 x 10(6)
      microns 3 at low altitude to 1.1 x 10(6) microns 3 at high altitude) whilst the
      star volume of intervillous pores increased 4-fold (from 87 x 10(6) microns 3 to
      461 x 10(6) microns 3). These figures imply that villous domains decrease in size
      but may be constant in number. The most likely explanation is that villous trees
      at high altitude are scaled-down versions of their low-altitude counterparts. By
      contrast, although the intervillous pores enlarge they may decrease in number in
      the highland organ. This may reflect a change in the number of maternal
      cotyledons or in the spatial arrangement of villous trees.

PMID- 7649835
TI  - A light and electron microscope study of rat abducens nucleus neurons projecting
      to the cerebellar flocculus.
AB  - Injection of horseradish peroxidase (HRP) into the cerebellar flocculus of the
      rat was employed to identify neurons in the abducens nucleus that project to the
      flocculus. The number, ultrastructural features and precise localisation of these
      neurons in the nucleus were examined. They were present bilaterally and
      represented about 7% of the total neuronal population of each nucleus. They were
      localised principally in the dorsomedial area of the cranial half of each nucleus
      and did not display the typical ultrastructural features of motoneurons. It is
      concluded that the localisation and ultrastructural characteristics of these HRP
      positive neurons are useful for distinguishing them from other neuronal
      populations within the nucleus.

PMID- 7649836
TI  - Is rabbit dentine innervated? A fine-structural study of the pulpal innervation
      in the cheek teeth of the rabbit.
AB  - The pulpal innervation of rabbit premolars and molars has been studied in
      transverse sections of perfusion-fixed, demineralised specimens using light
      microscopy and transmission electron microscopy. A mixed population of small
      myelinated and unmyelinated axons enters the apical foramen to supply the mesial
      and distal laminae of these continuously growing teeth. The nerve fibres are
      remote from the preodontoblasts and odontoblasts near the apical end, but in
      their passage to the occlusal end the pulp becomes progressively narrower and
      nerve fibres come to lie subjacent to the odontoblasts and postodontoblasts.
      Counts of myelinated fibres near the apical end and in the occlusal pulp
      suggested that the myelin is shed near the occlusal end. Most of the dentine in
      these teeth is tubular and migrates occlusally with supporting odontoblasts. Near
      the occlusal end, postodontoblasts deposit an atubular tissue which closes the
      pulpal ends of the tubules. Nearer the occlusal tip the pulpal contents
      degenerate and become embedded in the forming atubular tissue. Evidence of axon
      profiles was found near the occlusal end in the pulp, passing through the
      odontoblast layer and in the dentine tubules adjacent to odontoblast processes.
      However, many of the tubules contained an odontoblast process only and the
      atubular tissue was not innervated. Since innervated tubules eventually become
      closed by atubular tissue it is assumed that the nerve fibres retract from the
      tubules before their closure. In common with other teeth the function of the
      pulpal nerve supply is likely to be mostly nociceptive.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7649838
TI  - Comparative anatomical studies on the thyroid and thymic arteries. III. Guinea
      pig (Cavia cobaya).
AB  - The thyroid and thymic arteries were investigated in 30 male and 30 female
      Hartley guinea pigs. The superior thyroid artery was the most common (73% of
      males, 55% of females). It arose from the external carotid artery and gave rise
      to the superior and inferior laryngeal arteries in addition to glandular rami. In
      the remaining instances, the independence of the superior laryngeal resulted in
      the presence of middle and inferior thyroid arteries. The middle thyroid artery,
      arising from the external carotid or distal half of the common carotid artery,
      passed the thyroid gland cranially or penetrated it to terminate in the inferior
      laryngeal artery. The inferior thyroid artery, arising from the distal or
      proximal half of the common carotid, reached the gland caudally also to end in
      the inferior laryngeal. A thyroid ima artery was rare. There were many
      'independent thyroid arteries'. Some of them arose from the lingual and the
      ascending pharyngeal arteries, suggesting that they were the original thyroid
      arteries. Thus the thyroid arteries were much more abundant and variable in the
      guinea pig than in man. The arteries supplying the 'superficial cervical thymus',
      which is characteristic of this animal, were the superior and inferior
      superficial cervical thymic arteries. The latter artery, arising from the
      superficial cervical, appeared in about 30% of the specimens. The former was
      always present and arose from the lingual (75% of males, 67% of females);
      superior laryngeal, and superior thyroid or common carotid arteries. The cranial
      extension of the thymus and the superior superficial cervical thymic artery had
      complex relationships with the hypoglossal nerve.

PMID- 7649837
TI  - Changes in density of brainstem afferents in ferret primary auditory cortex (AI)
      during postnatal development.
AB  - Histochemical methods were used to assess the distribution of 4 neurotransmitters
      thought to be involved in cortical plasticity. They were measured in the primary
      auditory cortex of the ferret from just before the onset of hearing.
      Acetylcholinesterase staining was strongest in layers I, IV and VI and there was
      a gradual increase in the amount of staining from postnatal day (PND) 21 through
      to adulthood. Serotonin fibres were located mainly in layers I-III and their
      density increased gradually over the same time period. Noradrenergic fibres were
      sparsely scattered throughout the cortex but their density and distribution
      showed little change over the age range studied. Dopaminergic fibres were densest
      in layers V and VI at all ages. However, there was a transient doubling in their
      density that started round about the onset of hearing at PND 28, peaked at PND 35
      and had returned to baseline levels by 2 wk later. This transient peak in density
      did not occur in the adjacent suprasylvian gyrus and did not appear to be a
      general phenomenon. The local transient increase in dopaminergic fibres implies
      that they may have an important role during a short period in auditory cortical
      development. This role may involve modifying the cortical circuitry that is
      involved in analysing the input from the auditory periphery.

PMID- 7649839
TI  - The nerve supply to coracobrachialis in apes.
AB  - The origin of the nerve supply to coracobrachialis from the brachial plexus in
      apes was investigated in 4 arms from 4 chimpanzees, both arms of a gorilla and 4
      arms from 4 gibbons. The general architecture of the brachial plexus was the same
      as in the human. In the apes examined, the nerves supplying this muscle could be
      classified into 2 groups: (1) distal branches arising from the musculocutaneous
      nerve, and (2) proximal branches arising in the region of the lateral cord. On
      the basis of their origin and course, the proximal branches were classified into
      3 types, namely a deep ramus arising from the middle trunk and passing dorsal to
      the upper trunk, a medial ramus arising from the upper trunk in the lateral cord,
      and a superficial ramus arising from the ventral surface of the middle trunk or
      the root of the pectoral nerve. This classification also applies to branches to
      coracobrachialis in man. The 3 types of proximal branch often communicated with
      each other to supply coracobrachialis, whereas the proximal and distal branches
      were separated from each other spatially. This indicates that coracobrachialis
      possesses characteristics both of the pectoral girdle muscles and the flexor
      muscles of the upper arm.

PMID- 7649840
TI  - The renal veins in the human cadaveric fetus: their importance as contributors to
      collateral flow.
AB  - The venous collateral flow emanating from and around the renal veins was
      investigated in the human cadaveric fetus. Experimental venous occlusion was
      performed along several venous pathways under the sphere of influence of the
      renal veins in 11 fetuses. Radiological techniques were used to investigate renal
      venous collateral flow. Extensive venous collaterals centered on the left renal
      vein were observed. It is concluded that the left renal vein is a major venous
      collateral pathway in the fetus whereas the right renal vein contributes little.
      This potential for collateralisation may be operative in the adult and may play a
      dominant role in disease states.

PMID- 7649841
TI  - Granulated metrial gland cells in the uterine wall and placenta of the pregnant
      woodmouse, Apodemus sylvaticus.
AB  - The differentiation of the decidua and the fetal placenta in the woodmouse,
      Apodemus sylvaticus, was studied with particular attention to the differentiation
      and migration of granulated metrial gland cells. Numerous granulated metrial
      gland cells, characterised by their glycoprotein-containing cytoplasmic granules,
      were found to differentiate in the decidua basalis and metrial gland of the
      uterine wall during the first half of pregnancy. Many granulated metrial gland
      cells appeared to pass into the lumina of blood vessels in the uterine wall and
      reach the maternal blood spaces of the fetal placenta. In the labyrinthine
      placenta some granulated metrial gland cells were found associated with
      degenerate cytotrophoblast lining the maternal blood spaces. This finding
      supports previous studies of the mouse, Mus musculus, suggesting that the
      labyrinthine placenta is an important site for the function of the bone marrow
      derived granulated metrial gland cell.

PMID- 7649842
TI  - Variations in the quality of uncalcified fibrocartilage at the insertions of the
      extrinsic calf muscles in the foot.
AB  - It has been suggested that fibrocartilage at entheses (tendon-bone junctions)
      prevents collagen fibres bending at the hard tissue interface. We have
      investigated this function by exploring the relationship between the presence or
      amount of fibrocartilage at the attachments of the major extrinsic muscles in the
      foot, and the extent to which these tendons bend near their entheses during
      movement. The tendons were taken from each of 5 formalin-fixed dissecting room
      cadavers and prepared for routine histology, and sections were collected
      systematically throughout the blocks. Tendons that attached to the tarsus and
      metatarsus had fibrocartilaginous entheses, but those attached to the phalanges
      had fibrous entheses. In all tarsal and metatarsal tendons, the fibrocartilage
      was significantly thicker (P < 0.05) in the deepest part of the enthesis. Here
      the greatest amount of fibrocartilage was in the Achilles tendon (mean thickness
      +/- S.E.M.: 1560 +/- 161 microns). There were moderate amounts at the medial
      cuneiform attachment of tibialis anterior (533 +/- 82 microns), peroneus brevis
      (472 +/- 64 microns) and tibialis posterior (454 +/- 26 microns), small
      quantities at the first metatarsal attachment of tibialis anterior (104 +/- 14
      microns) and peroneus longus (21 +/- 8 microns), but only traces at the
      attachments of the flexor and extensor tendons of the phalanges. The differences
      can be related to variations in the freedom of movement of the tendons near their
      attachments. This depends on the extent to which the tendons are bound by
      retinacula and the range of movement of the joint nearest the enthesis. The
      results suggest that more 'mobile' tendons have more fibrocartilage.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7649843
TI  - Anatomical study of the opossum (Didelphis albiventris) extraocular muscles.
AB  - The anatomy of the extraocular muscles was studied in 10 adult opossums
      (Didelphis albiventris) of both sexes. Eight extraocular muscles were identified:
      4 rectus muscles, 2 oblique muscles, the levator palpebrae superioris and the
      retractor ocular bulbi. The rectus muscles originate very close one to another
      between the orbital surfaces of the presphenoid and palatine bones. These muscles
      diverge on the way to their insertion which occurs at about 2 mm from the limbus.
      The levator palpebrae superioris originates with the dorsal rectus and is
      positioned dorsally in relation to it. The retractor ocular bulbi forms a cone
      which embraces the optic nerve and is located internally in relation to the
      rectus muscles. The dorsal oblique originates on the presphenoid bone and after a
      tendinous trajectory through a trochlea on the medial wall of the orbit, inserts
      into the ocular bulb. The only muscle arising from the anterior orbital floor is
      the ventral oblique. The main nerve supply for these muscles is the oculomotor,
      except for the dorsal oblique which is innervated by the trochlear nerve, and the
      lateral rectus which is innervated by the abducens nerve. The retractor ocular
      bulbi receives branches from the inferior division of the oculomotor nerve and
      some branches from the abducens nerve.

PMID- 7649844
TI  - Morphology of the torn rotator cuff.
AB  - The morphological characteristics of shoulders with torn rotator cuffs were
      determined using 41 embalmed specimens. The following parameters were measured in
      the supraspinatus (SSP), infraspinatus (ISP) and subscapularis (SSC) muscles: the
      length, thickness and width of the extramuscular tendon; the length of the
      intramuscular tendon; the length and width of a tear, if present, muscle fibre
      length; and muscle volume. The cross-sectional area (CSA) of the tendon was
      measured on the photographic image of slices of the tendon using an image
      analysis system, and the CSA of the muscle was calculated by dividing the muscle
      volume by muscle fibre length. The rotator cuff was intact in 11 shoulders. A
      partial-thickness tear of the cuff was present in 12 shoulders, a full-thickness
      tear of the SSP in 11 shoulders, and a full-thickness tear of more than 2 tendons
      in 7. Overall incidence of full-thickness tears of the rotator cuff was 44%, and
      that of partial-thickness tears 29%. With increase of tear size, the functional
      tendon length (extramuscular tendon length plus tear length) increased by a
      statistically significant amount in the SSP, ISP and SSC, whereas muscle fibre
      length decreased in SSP and ISP. It is concluded that the increased functional
      tendon length and decreased muscle fibre length are the main morphological
      changes that make the rotator cuff a physiologically abnormal unit. Surgical
      repair of the torn cuff would be expected to improve these anatomical changes and
      restore the kinetics of the glenohumeral joint.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7649845
TI  - The morphology and innervation of the lateral pterygoid muscle of the dog.
AB  - The number of heads possessed by the lateral pterygoid muscle was investigated in
      the dog. Only a single head was observed which it is suggested may correspond to
      the lower head in other mammals. It inserted both onto the condyle and into the
      articular disc. The nerve which innervated this muscle arose directly from the
      mandibular nerve, separate from the medial pterygoid nerve. Because of this, it
      should be termed the lateral pterygoid nerve and not the pterygoid nerve.

PMID- 7649846
TI  - Distribution patterns of the muscular branch of the median nerve in the thenar
      region.
AB  - Studies on the distribution patterns of the muscular branch of the median nerve
      to the thenar muscles are scarce. Available accounts give only general
      descriptions. To establish the distribution pattern more precisely, we dissected
      60 palmar regions from 30 cadavers of adult individuals, ranging in age from 23
      to 77 y. The distribution pattern of the muscular branch was classified into 3
      types. In 50% of subjects there were branches to the superficial head of flexor
      pollicis brevis (FPB), abductor pollicis brevis (APB) and opponens pollicis (OP)
      (type I). In 40% there were branches only to APB and OP (type II). In the
      remainder (type III) the muscular branch provided independent branches to APB, OP
      and FPB, to APB and OP, or to APB and FPB, after dividing precociously. Types I
      and II were further subdivided according to the site, direction and number of the
      individual branches.

PMID- 7649847
TI  - Fibre composition of rabbit tibialis anterior and extensor digitorum longus
      muscles.

PMID- 7649848
TI  - Michael Fordham (1905-1995).

PMID- 7649849
TI  - Staurosporine, a potentially important gift from a microorganism.

PMID- 7649850
TI  - Control of avermectin biosynthesis in Streptomyces avermitilis for the selective
      production of a useful component.

PMID- 7649851
TI  - Linking peptide and polyketide biosynthesis.

PMID- 7649852
TI  - Xenovulene A, a novel GABA-benzodiazepine receptor binding compound produced by
      Acremonium strictum.
AB  - Xenovulene A, a novel inhibitor of benzodiazepine binding to the GABA
      benzodiazepine receptor is produced by submerged fermentation of Acremonium
      strictum. It was isolated from the mycelium by solvent extraction and purified by
      chromatography on Sephadex LH-20 and octadecyl silica. The structure of
      xenovulene A was determined to be a novel oxygenated sesquiterpene containing a
      humulene moiety by interpretation of various spectroscopic data, especially from
      2D NMR experiments. Xenovulene A inhibited binding of the benzodiazepine,
      flunitrazepam, with an IC50 of 40 nM in an in vitro assay using bovine
      synaptosome membrane preparations.

PMID- 7649853
TI  - A new neuronal cell protecting substance, lavanduquinocin, produced by
      Streptomyces viridochromogenes.
AB  - A new neuronal cell protecting substance, lavanduquinocin was isolated from
      Streptomyces viridochromogenes 2942-SVS3. It consists of a carbazole skeleton
      with an ortho quinone function and a cyclolavandulyl moiety. Lavanduquinocin
      protected neuronal hybridoma N18-RE-105 cells from L-glutamate toxicity with EC50
      value 15.5 nm.

PMID- 7649854
TI  - Synthesis and biological activities of TAN-1511 analogues.
AB  - TAN-1511 analogues were synthesized and their effects on the proliferation of
      bone marrow cells were examined. To exert potent activity the following
      conditions are necessary: the configuration of the 2-amino-6,7-dihydroxy-4
      thiaheptanoic acid moiety must be (2R,6R), long chain acyl groups (C14 to C18)
      must be bound to both hydroxyl groups, the amino group must be free or acylated
      with the long chain fatty acid (ca. C14) and the peptide moiety must have
      glutamic acid as a component. Among the synthesized compounds, trisodium (2R,6R)
      2-amino-6,7-bis (hexadecanoyloxy)-4-thiaheptanoyl glycyl glutamyl glutamate,
      which has improved solubility, was effective in experimental leukocytopenia in
      mice.

PMID- 7649855
TI  - Isolation from Streptomyces of a novel naphthoquinone compound, naphthablin, that
      inhibits Abl oncogene functions.
AB  - In the course of our screening for inhibitors of abl oncogene function, a culture
      filtrate of Streptomyces aculeolatus, induced normal flat morphology in v-abl
      expressing NIH3T3 cells. The active substance was isolated through ethyl acetate
      extraction, silica gel column chromatography, and reverse-phase HPLC. Mass and
      NMR spectroscopy including HMBC revealed that it had a novel naphthoquinone
      structure with a monoterpene, and we named it "naphthablin". Naphthablin
      inhibited Abl-induced morphological transformation in v-ablts-NIH3T3 cells at
      around 30 micrograms/ml, and specifically inhibited RNA synthesis.

PMID- 7649856
TI  - Fusacandins A and B; novel antifungal antibiotics of the papulacandin class from
      Fusarium sambucinum. I. Identity of the producing organism, fermentation and
      biological activity.
AB  - The fuscandins, antifungal agents of the papulacandin class, are produced by a
      strain of Fusarium sambucinum. Fermentation yielded 60 mg/liter of fusacandin A
      and minor amounts of fusacandin B. As expected, the fusacandins inhibit (1,3)
      beta-glucan synthesis. Fusacandin A is slightly less active than papulacandin B
      against Candida albicans and, like papulacandin, loses activity in the presence
      of serum.

PMID- 7649857
TI  - Fusacandins A and B; novel antifungal antibiotics of the papulacandin class from
      Fusarium sambucinum. II. Isolation and structural elucidation.
AB  - Two novel antifungal compounds of the papulacandin class, named fusacandins A and
      B, have been isolated from Fusarium sambucinum. Each compound contains two units
      of galactose and one of glucose, the latter connected as a C-glycoside to an
      aromatic moiety. Fusacandin A is esterified at two sites with long-chain,
      unsaturated fatty acids and fusacandin B at only one site. The structures of the
      fusacandins were elucidated through analysis of mass spectral and 1-D and 2-D
      homonuclear and heteronuclear NMR data.

PMID- 7649858
TI  - Biosynthetic capacities of actinomycetes. 4. Echinoserine, a new member of the
      quinoxaline group, produced by Streptomyces tendae.
AB  - A new member of the quinoxaline group antibiotics has been detected by HPLC-diode
      array screening. The main compound produced by Streptomyces tendae strain Tu 4031
      showed a high degree of similarity in the UV-visible spectral region with
      echinomycin and their structural similarity was confirmed by structure
      elucidation using electron tandem mass spectrometry and 2D nuclear magnetic
      resonance. The new compound, named echinoserine, is a non-cyclic form of
      echinomycin, but it is not a biosynthetic precursor. Echinoserine is less
      antibiotically active than echinomycin.

PMID- 7649859
TI  - Gualamycin, a novel acaricide produced by Streptomyces sp. NK11687. I. Taxonomy,
      production, isolation, and preliminary characterization.
AB  - A novel acaricide, gualamycin, was isolated from the culture broth of
      Streptomyces sp. NK11687. It was purified from the filtrate by column
      chromatographies. Gualamycin showed 100% acaricidal activity at 250 micrograms/ml
      against sensitive and resistant mites to Dicofol.

PMID- 7649860
TI  - Gualamycin, a novel acaricide produced by Streptomyces sp. NK11687. II.
      Structural elucidation.
AB  - A novel acaricide, gualamycin was isolated from the culture broth of Streptomyces
      sp. NK11687. The structure of gualamycin was determined to be (2R,3S,4S)-2-O-[4-O
      (2-amino-2-deoxy-beta-D-gulopyranosyl)-alpha-D - galactopyranosyl]-2,3,4
      trihydroxy-4-[(2S,3S,4S,5S)-3,4-dihydroxy-5-hydr oxy - methylpyrrolidin-2-yl]
      butanoic acid by FAB-MS, 1H and 13C NMR, COSY, HMQC, HMBC, IR, X-ray
      crystallographic analyses and synthetic studies.

PMID- 7649861
TI  - Direct transfer of plasmid DNA between Streptomyces spp. and E. coli by
      electroduction.
AB  - We describe a simple and reliable method which allows the direct transfer of
      shuttle plasmids between Streptomyces spp. and E. coli. The method is based on
      the fact that plasmid DNA molecules can be released or taken up from cells under
      conditions of electroporation. When a suspension of a plasmid-containing
      Streptomyces spp. is mixed with electroporation-competent E. coli and submitted
      to an electric pulse, plasmid DNA transfer to the E. coli recipient takes place.
      Two different Streptomyces spp. (S. lividans TK23, or TK24 and S. rimosus 554w)
      were effective donors, and the method was successfully employed to transfer four
      different bifunctional vectors (pPM801, pFD666, pRL270X and pZG5) varying in size
      from 5.2-14.4 kb, to E. coli. This provides a convenient method for the analysis
      of Streptomycete transformants.

PMID- 7649862
TI  - Overexpression of a gene cluster encoding a chalcone synthase-like protein
      confers redbrown pigment production in Streptomyces griseus.
AB  - A 7.0-kb DNA fragment that conferred redbrown pigment production on Streptomyces
      griseus was shotgun-cloned with a multicopy vector pIJ486 from this
      microorganism. By restriction endonuclease mapping and subcloning, a 1.5-kb
      fragment which is essential for the production of redbrown pigment was
      determined. The nucleotide sequence of this region revealed the presence of two
      open reading frames, ORF1 with 109 amino acids (named RppA) and ORF2 with 262
      amino acids (RppB), in addition to a truncated ORF3. The termination codon of
      rppA and the initiation codon of rppB overlapped, sharing one common nucleotide,
      which strongly suggests that these two genes are cotranscribed. Both rppA and
      rppB were essentially required for the pigmentation. The RppB protein showed
      great similarity in amino acid sequence to a chalcone synthase, a key enzyme of
      central importance in the biosynthetic pathway of all classes of flavonoids in
      plants. Part of RppA showed sequence similarity to the 33kDa phosphoprotein of
      adenovirus. Nucleotide sequences homologous to rppA and rppB were widely
      distributed in Streptomyces species, as determined by Southern hybridization.
      Further nucleotide sequencing of the entire orf-3 gene showed that ORF3 with 403
      amino acids was a cytochrome P-450 (named P-450RPP). These data suggested that
      the cloned fragment contained part of a gene cluster for the biosynthesis of a
      certain metabolite. Introduction of the subcloned 1.5-kb fragment into
      Streptomyces lividans as well as Escherichia coli also caused production of
      redbrown pigment, suggesting that RppA and RppB are capable of synthesizing the
      redbrown pigment from metabolites commonly present in bacteria.

PMID- 7649863
TI  - Erythromycin biosynthesis. Highly efficient incorporation of polyketide chain
      elongation intermediates into 6-deoxyerythronolide B in an engineered
      Streptomyces host.
AB  - Feeding of (2S,3R)-[2,3-13C2]-2-methyl-3-hydroxypentanoyl NAC thioester (1a) to
      the recombinant organism Streptomyces coelicolor CH999/pCK7 harboring the
      complete set of eryA genes from Saccharopolyspora erythraea encoding the 6
      deoxyerythronolide B synthase (DEBS) resulted in the formation of 6
      deoxyerythronolide B (2a) labeled with 13C at C-12 and C-13, as evidenced by the
      appearance of a pair of enhanced and coupled doublets in the 13C NMR spectrum.
      The level of 13C enrichment was 15-20 atom% 13C, as much as 100 times higher than
      the usually observed efficiency of incorporation of NAC thioesters into
      polyketide metabolites. Similar incorporation of (2S,3R)-[3-2H,3-13C]-2-methyl-3
      hydroxypentanoyl NAC thioester (1b) gave 6-deoxyerythronolide B (2b) labeled with
      both 13C and deuterium at C-13. The intact incorporation of both precursors
      confirms the normal functioning of the recombinant DEBS proteins in the
      heterologous host.

PMID- 7649864
TI  - Cytosinine: pyridoxal phosphate tautomerase, a new enzyme in the blasticidin S
      biosynthetic pathway.
AB  - Cytosinine--the nucleoside portion of blasticidin S--and pyridoxal phosphate were
      incubated with cell-free extracts of Streptomyces griseochromogenes prepared in
      D2O. 2H NMR analysis of recovered cytosinine showed it to contain deuterium
      enrichments at H-4' and H-2'. No exchange was observed with either boiled extract
      or from cytosinine and pyridoxal phosphate alone. These results reveal the
      presence of a tautomerase activity that contributes to the net transamination at
      C-4' in the conversion of cytosylglucuronic acid to blasticidin S, and its
      discovery supports the role of cytosinine as a biosynthetic intermediate.

PMID- 7649866
TI  - Chemical modification of tylosin.
AB  - 20-Homo tylosin, 20-nor tylosin, 20-deoxy-19,20-didehydro tylosin (6-vinyl
      tylosin) and 2",3"-didehydro-3"-deoxy tylosin were prepared by multi-step
      procedures. 20-Homo tylosin was about twice less active than tylosin while the
      other compounds exhibited very weak antibacterial activity.

PMID- 7649865
TI  - Generation of novel rapamycin structures by microbial manipulations.
AB  - A new rapamycin producing culture was isolated and designated as Actinoplanes sp.
      N902-109. The addition of a cytochrome P-450 inhibitor and precursor feeding
      using this culture, and biotransformation approaches generated new rapamycin
      analogs with modifications at C-4, C-9, C-16, C-27, C-28 and/or C-39. The
      immunosuppressive activity of the resulting analogs was established in the mixed
      lymphocyte reaction assay.

PMID- 7649868
TI  - Unusual transformation of the 3-hydroxy-picolinoyl residue of pristinamycin IA.
AB  - Pristinamycin IA was modified in a two-step procedure to give original
      derivatives possessing a tricyclic nucleus (8a, 8b, 8c) or a substituted pyrrole
      ring (10a, 10b) in place of the natural exocyclic 3-hydroxy-picolinoyl residue.
      This transformation involved firstly preparation of pyridinium betaines 5 from
      pristinamycin IA and secondly a 1-3 dipolar cycloaddition between 5 and N
      substituted maleimides or diethyl acetylenedicarboxylate. The compounds obtained
      were evaluated as antibacterial agents alone and in association with
      pristinamycin IIA.

PMID- 7649867
TI  - Synthesis, antimicrobial activity and in vivo fluorine NMR of a hexafluorinated
      derivative of tilmicosin.
AB  - A new fluorinated analog of tilmicosin was synthesized by the reductive amination
      of desmycosin with 3,5-bis(trifluoromethyl)piperidine. Despite an apparently
      small change in structure, the fluorinated analog had much less in vitro
      antimicrobial activity than tilmicosin and it failed to protect 3-day old chicks
      against a Pasteurella multocida challenge at 64 mg/kg sc. In a preliminary in
      vivo fluorine NMR experiment in a female Sprague-Dawley rat, a 19F NMR signal was
      detected in the liver one hour after ip administration of the fluorinated
      compound. Therefore, although this fluorinated derivative had less antimicrobial
      activity than tilmicosin, it may nevertheless provide a suitable model of
      tilmicosin for pharmacokinetic studies using in vivo fluorine NMR.

PMID- 7649869
TI  - Synthesis of new pseudodisaccharide aminoglycoside antibiotics from
      carbohydrates.
AB  - Novel pseudodisaccharide-type aminocyclitol antibiotic models, built up from D
      arabinose, D-ribose, D-glucosamine, L-ristosamine and L-acosamine have been
      synthesized by the glycosylation of suitably protected (azido)deoxyinosose
      aglycones derived by the Ferrier carbocyclic ring transformation of carbohydrate
      precursors. An alternative approach to related pseudodisaccharides, based on the
      Ferrier carbocyclization of reducing disaccharides, has also been elaborated.
      This latter method extends the scope of the Ferrier reaction, by demonstrating
      that acid-labile 2-deoxydisaccharides can also be readily transformed into the
      corresponding pseudodisaccharides under the slightly acidic conditions of this
      ring-transformation.

PMID- 7649870
TI  - Isochromophilones III-VI, inhibitors of acyl-CoA:cholesterol acyltransferase
      produced by Penicillium multicolor FO-3216.
AB  - New azaphilones named isochromophilones III-VI were isolated from the culture
      broth of Penicillium multicolor FO-3216 as inhibitors of acyl-CoA: cholesterol
      acyltransferase (ACAT). Their structures were elucidated by NMR and other
      spectroscopic analyses. The IC50 values of isochromophilones III, IV, V and VI
      for ACAT activity in an enzyme assay using rat liver microsomes were calculated
      to be 110, 50, 50 and 120 microM, respectively.

PMID- 7649871
TI  - Isochromophilones I and II, novel inhibitors against gp120-CD4 binding produced
      by Penicillium multicolor FO-2338. I. Screening, taxonomy, fermentation,
      isolation and biological activity.
AB  - Isochromophilones I and II, the first novel gp120-CD4 binding inhibitors of
      microbial origin, were isolated from a cultured broth of a soil fungus designated
      as Penicillium multicolor FO-2338. These compounds were obtained as yellow
      powders from the cultured broth together with the known related compounds
      sclerotiorin, ochrephilone and rubrorotiorin. Isochromophilones I and II
      (C23H25O5Cl and C22H27O4Cl, respectively) have an azaphilone skeleton and a
      chlorine atom. Isochromophilones strongly inhibited gp120-CD4 binding (IC50: 6.6
      and 3.9 microM, respectively), but the other related compounds did not.
      Isochromophilone II inhibited significantly HIV replication in peripheral human
      lymphocytes at 25 microM.

PMID- 7649872
TI  - Isochromophilones I and II, novel inhibitors against gp120-CD4 binding produced
      by Penicillium multicolor FO-2338. II. Structure elucidation.
AB  - The structures of isochromophilones I and II, new gp120-CD4 binding inhibitors
      isolated from a cultured broth of Penicillium multicolor FO-2338, were elucidated
      by NMR experiments. Both of compounds have an azaphilone skeleton substituted by
      a chlorine atom at C-5 and a side chain, 3,5-dimethyl-1,3-heptadien at C-3.
      Additionally, isochromophilone I has a gamma-lactone ring, and isochromophilone
      II has 2-oxopropyl moiety instead of a gamma-lactone ring.

PMID- 7649873
TI  - New antibiotics phthoxazolins B, C and D produced by Streptomyces sp. KO-7888.
AB  - New antibiotics, phthoxazolins B, C and D were isolated from the fermentation
      broth of Streptomyces sp. KO-7888. They are geometrical isomers of 10
      hydroxyphthoxazolin A. They showed selective antifungal activity against
      Phytophthora parasitica in vitro and modest herbicidal activity in a laboratory
      test, but the potencies were different among isomers.

PMID- 7649874
TI  - Screening method for cellulose biosynthesis inhibitors with herbicidal activity.
AB  - A new screening method for inhibitors of cellulose biosynthesis is described.
      This method utilized three microbial strains; a cellulose-containing fungus
      Phytophthora, and a cellulose non-containing fungus Candida, and a bacterial
      strain of Acetobacter, a cellulose-producing acetic acid bacterium. The primary
      screen examined microbial cultures for selective growth inhibition against
      Phytophthora with no inhibition against Candida. The secondary screen tested for
      herbicidal activity. Thirdly, the active cultures were examined for their
      inhibition of cellulose biosynthesis by an Acetobacter strain. A screening trial
      with this new method led to the discovery of two microbial metabolites named
      phthoxazolin A and phthoramycin as new inhibitors of cellulose biosynthesis with
      herbicidal activity.

PMID- 7649875
TI  - Favolon, a new antifungal triterpenoid from a Favolaschia species.

PMID- 7649876
TI  - Stereoselective deoxygenation of erythromycin A at C-12: effect of structure and
      conformation on prokinetic activity.

PMID- 7649877
TI  - Epolactaene, a novel neuritogenic compound in human neuroblastoma cells, produced
      by a marine fungus.

PMID- 7649878
TI  - RPR113228, a novel farnesyl-protein transferase inhibitor produced by
      Chrysosporium lobatum.

PMID- 7649879
TI  - Photoactivation of neocarzinostatin chromophore: photo-induced cycloaromatization
      via naphthoate participation.

PMID- 7649880
TI  - Syntheses and absolute structures of the disaccharide and aglycone of acaricidal
      gualamycin.

PMID- 7649881
TI  - Arisugacin, a novel and selective inhibitor of acetylcholinesterase from
      Penicillium sp. FO-4259.

PMID- 7649882
TI  - Structure-activity relationships of lactacystin, the first non-protein
      neurotrophic factor.

PMID- 7649883
TI  - Structure-activity relationships of pyripyropenes fungal acyl-CoA: cholesterol
      acyltransferase inhibitors.

PMID- 7649884
TI  - Story.

PMID- 7649885
TI  - Health issues among Afghan women in California.
AB  - Afghan refugee women are part of the largest refugee population in the world. In
      the United States, they deal with loss of family members, property, and status
      and cultural, familial, religious, role, and generational conflict in making the
      transition from a traditional patriarchal society to a more egalitarian
      postindustrial society. Findings from a San Francisco Bay Area Afghan community
      health assessment conducted from 1992 to 1993 are presented. The assessment
      included 38 telephone interviews, seven community meetings, and a survey of 196
      Afghan families. Six years of ethnographic study with more than 200 Afghans and
      their health providers provide contextual data. We describe cultural
      characteristics that influence women's access to health care, women's approach
      toward preventive care, control of information regarding sexuality, and spouse
      abuse.

PMID- 7649886
TI  - Women and somatization: unrecognized depression.
AB  - Depression is the mental health disorder most commonly seen in the primary health
      care setting. Estimates of the prevalence of people who are depressed but are
      seeking treatment for physical disorders in the primary care setting range from
      12% to 55% of total patients. We conducted a study to determine the number of
      women with high depressive symptoms who were seeking treatment for physical
      disorders and compared this group with women with no depressive symptoms who were
      also seeking physical health care. The women with high depressive symptoms (n =
      122) and the women with no depressive symptoms (n = 115) were similar in age,
      economic status, occupation status, and lifestyle. The depressed women reported
      significantly more physical complaints, increased disability, increased
      functional limitations, and increased use of health care services than did the
      nondepressed women. They disclosed a variety of physical complaints in all organ
      systems, had had more life events, and had a diminished belief in their ability
      to control their environments. The results of this study support the view that
      large numbers of women with depression that is unrecognized present themselves to
      the health care system for physical complaints. Health care providers need to
      extend their view of women as whole beings, instead of as a somatic complaint.

PMID- 7649887
TI  - Primary care in Cuba: a public health approach.
AB  - Cuba's primary health care model is presented. Unlike ambulatory care services,
      which are but one component of primary care, Cuba's model is a comprehensive
      public health approach that meets the World Health Organization's definition of
      primary care. The history of the development of Cuba's model is presented,
      including an update on the innovative neighborhood/home clinics. Achievements in
      health outcomes as a result of Cuba's model and the consequences for women's
      health care are discussed. Examples are presented of the effects on health care
      delivery of the economic hardship that Cuba has experienced since 1991 as a
      result of the loss of 85% of its trade with the former Soviet Union and the
      intensified U.S. embargo. A critique of Cuba's model concludes the article.

PMID- 7649888
TI  - Setting and provider of prenatal care: association with pregnancy outcomes among
      low-income women.
AB  - Although the importance of prenatal care is widely recognized, little is known
      about the impact of different models of care on health outcomes. We examined the
      relationships of setting and provider of prenatal care to birth outcomes among
      low-income women in a predominantly rural county in the northwest United States.
      Three study populations were compared: all women who received care from certified
      nurse-midwives (CNMs) at a hospital-based prenatal clinic; all Medicaid
      recipients who obtained care from CNMs in private practice; and a randomly
      selected sample of Medicaid recipients who obtained care from physicians in
      private practice. Data on sociodemographics, prenatal care use, health
      indicators, and birth outcomes were collected from birth certificates. When other
      factors known to affect birth weight were controlled through multiple regression
      analyses, results indicated that receiving care from CNMs and receiving care in
      the private setting were related to higher mean infant birth weight.

PMID- 7649889
TI  - Cost-effectiveness of antenatal screening for syphilis.
AB  - Routine obstetric screening for all prenatal checkups is an important issue. A
      study was conducted to ascertain the effectiveness of an antenatal screening
      program for syphilis. Charts of pregnant women for a 9-year period from 1982 to
      1990 at the American University of Beirut were reviewed. Demographic data and the
      results of screening for syphilis were collected. In a total of 23,145 patients
      screened (with a biological false-positive rate of 0.3%), serological evidence of
      Treponema pallidum infection occurred in 0.27% of patients. The outcome in
      infants was satisfactory in all cases where appropriate antibiotic therapy was
      instituted antenatally. Thus antenatal screening for syphilis in our setting is a
      cost-effective program.

PMID- 7649890
TI  - Health responsibility and workplace health promotion among women: early detection
      of cancer.
AB  - The importance of health responsibility as one aspect of a health-promoting
      lifestyle has been emphasized repeatedly. Yet there are only a few empirical
      studies of its role in preventive behavior. We examined the relationship between
      health responsibility and early-detection practices for breast and cervical
      cancer. A group of 253 women employees of a large industrial company participated
      in a cancer screening program subsidized by the employer. They completed
      questionnaires assessing health responsibility and reported early-detection
      practices: frequency of breast self-examination and physician breast
      examinations, frequency of Pap tests, and time lapsed since last Pap test and
      breast examinations. Health responsibility was a significant independent
      predictor of breast examination indicators but not of Pap tests. Education level
      was an important predictor for Pap tests, and age predicted most early-detection
      practices. The findings lend some support to the role of health responsibility in
      initiating breast examinations. Better prediction of early-detection practices
      could be achieved by adding cognitive and emotional components to the existing
      responsibility scale and by distinguishing between retrospective and prospective
      responsibility.

PMID- 7649891
TI  - Therapeutic aspects of aerobic dance participation.
AB  - An ethnographic analysis of aerobic dance exercise culture was conducted to
      determine the impact of the culture on the mind-body connection. After a review
      of the predominant theories on the relationship between vigorous exercise and
      elevated mood, aerobic dance participants' experiences are reported to illustrate
      how cognitive experience and self-esteem may be influenced. Interviews revealed
      that some participants achieved a pleasantly altered state of consciousness and
      respite from depression and stress. The relationship of the work ethic to
      achievement of participant satisfaction is underscored.

PMID- 7649892
TI  - Genital human papillomavirus infection: common but not trivial.
AB  - One of the most prevalent sexually transmitted diseases is genital human
      papillomavirus (HPV) infection. Because of its potentially serious consequences
      for women, HPV infection is receiving a significant amount of attention from
      researchers and clinicians. We summarize the research and clinical literature on
      HPV infection. The nature of the virus, the prevalence of HPV infection, and
      modes of transmission are discussed. Both the physiological and psychological
      consequences of the infection are explored. Perspectives on treatment are
      examined, and suggestions for psychoeducational interventions are offered.

PMID- 7649893
TI  - Chinese mothers' reactions to their child's chronic illness.
AB  - Improvements in health status in the People's Republic of China have led to a
      shift in the burden of illness from acute, communicable disease to long-term
      illness, particularly in urban areas. The Chinese family's response to chronic
      illness is influenced by many factors, including the traditional cultural value
      of family responsibility as well as economic determinants. Through direct
      interviews with 75 women, we sought to understand the financial, social,
      emotional, and physical effects of caring for a chronically ill child on a
      Chinese mother's life and caregiving ability and to identify the sources of
      support available to her.

PMID- 7649894
TI  - "O2 dependence of pregnenolone and aldosterone synthesis in mitochondria from
      bovine zona glomerulosa cells".

PMID- 7649895
TI  - O2 dependence of pregnenolone and aldosterone synthesis in mitochondria from
      bovine zona glomerulosa cells.
AB  - Hypoxia in vivo results in a decrease in aldosterone not accounted for by extra
      adrenal controllers. We have demonstrated that aldosteronogenesis but not
      cortisol synthesis in the whole cell is O2 sensitive. In the intact glomerulosa
      cell, this sensitivity is located in the late pathway step catalyzed by
      conversion of corticosterone to aldosterone (P-450aldo), whereas the early
      pathway catalyzed by conversion of cholesterol to pregnenolone (P-450scc) is not
      inhibited until PO2 is very low. Because P-450aldo and P-450scc are mitochondrial
      enzymes that depend on the same NADPH-specific electron transport proteins, we
      hypothesized that O2 sensitivity would be independent of energy production and
      expressed in isolated mitochondria. We measured the conversion of exogenous
      25(OH)-cholesterol to pregnenolone and of exogenous corticosterone to aldosterone
      in the presence of cyanoketone in mitochondria isolated from bovine zona
      glomerulosa cells and exposed to an experimental gas (1-100% O2) vs. a room air
      control. Pregnenolone production was not affected until PO2 was < 35 Torr and
      decreased to almost nil when PO2 was < 30 Torr. In contrast, aldosterone
      production increased under hyperoxia and decreased under moderate decreases in
      O2. The conversion of corticosterone to aldosterone was maintained at
      approximately 50% of control, even when PO2 was < 20 Torr. The sensitivity of the
      aldosterone pathway to changes in O2 within the physiological range appears to
      reside in the mitochondrial late pathway (i.e., P-450aldo) and is not
      significantly influenced by cytosolic regulators of steroidogenesis or by
      limitation of reducing equivalents.

PMID- 7649896
TI  - Effect of hepatic vagotomy on plasma catecholamines during exercise-induced
      hypoglycemia.
AB  - The existence of a hepatosympathetic reflex active during insulin-induced
      hypoglycemia has recently been reported. The purpose of the present investigation
      was to test the hypothesis that the liver, through the afferent innervation of
      the vagus nerve, contributes to plasma epinephrine and norepinephrine responses
      during exercise-induced hypoglycemia. Hepatic vagotomized and sham-operated rats
      were killed at rest or after 30, 60, and 120 min of running exercise (26 m/min,
      0% grade). At the end of the 120-min exercise period, liver glycogen, glucose,
      and insulin levels measured in the portal and peripheral plasma were all
      significantly reduced (P < 0.05) while epinephrine and norepinephrine
      concentrations, beta-hydroxybutyrate, lactate, and portal and peripheral glucagon
      plasma levels were all significantly increased (P < 0.05). However, no
      significant differences were observed between hepatic vagotomized and sham
      operated rats at rest and after exercise for the metabolic and hormonal
      responses. These results suggest that if a hepatosympathetic reflex is active
      during an exercise-induced hypoglycemia situation, then this contribution is
      probably hidden by more important regulatory mechanisms.

PMID- 7649897
TI  - Attenuation of hyperoxic lung injury by the 21-aminosteroid U-74389G.
AB  - Hyperoxic lung injury is attributable to oxygen radicals produced under hyperoxic
      conditions. The 21-aminosteroid (AS), U-74389G, is a potent antioxidant. We
      examined the effect of U-74389G on lung injury in guinea pigs during exposure to
      90% O2 for 48 h. We injected either vehicle or 10 mg/kg of U-74389G 30 min before
      the O2 exposure and injected the same dose 12, 24, and 36 h later. We performed
      two series of experiments after exposure. In the first series, we measured the
      clearance rate of 99mTc-labeled dialdehyde starch (DAS) from the lungs as an
      index of pulmonary epithelial damage in three experimental groups consisting of
      1) control (n = 6) O2 alone (n = 6), and 3) O2 + AS (n = 6). In the second
      series, pulmonary endothelial injury was estimated by using 28 guinea pigs
      divided into four experimental groups consisting of 1) control (n = 8), 2) AS
      alone (n = 5), 3) O2 alone (n = 6), and 4) O2 + AS (n = 9). In the second series,
      we measured the wet-to-dry weight ratio (W/D) as an index of lung water and the
      concentration ratio of 125I-labeled albumin in lung tissue and bronchoalveolar
      lavage (BAL) fluid compared with plasma (T/P and BAL/P, respectively) as indexes
      of pulmonary endothelial damage. Cell accumulation in BAL fluid and lung tissue
      samples was also assessed in the second series.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7649898
TI  - Role of EDRF in the cardiopulmonary dysfunction produced by massive sympathetic
      activation.
AB  - This study was undertaken to determine whether endothelium-derived relaxing
      factor (EDRF) modulates the pulmonary and systemic hemodynamic responses to
      massive sympathetic nervous system (SNS) activation and, in so doing, also
      modulates the degree of SNS-induced left ventricular (LV) dysfunction and the
      likelihood for pulmonary edema formation. The SNS of 13 anesthetized untreated
      rabbits and 14 anesthetized rabbits pretreated with the EDRF inhibitor, N omega
      nitro-L-arginine (L-NNA, 20 mg/kg), was massively activated with an
      intracisternal injection of veratrine. Pulmonary and systemic arterial pressures
      increased to the same extent in both groups, but LV end-diastolic pressure was
      significantly lower in untreated rabbits. During this time, cardiac output
      decreased by 37% in L-NNA pretreated rabbits compared with 8% in untreated
      animals. Peak systemic and pulmonary vascular resistances increased significantly
      in L-NNA rabbits, whereas only systemic vascular resistance increased
      significantly in untreated rabbits. However, this increase in systemic vascular
      resistance was threefold less than that observed for L-NNA-treated animals.
      Although the degree of LV dysfunction was greater in the L-NNA rabbits, pulmonary
      edema developed less frequently in this group. We suggest that when EDRF release
      is inhibited during massive SNS activity, pulmonary vascular resistance increases
      markedly, which causes the right ventricle to fail. We further suggest that the
      reduced right ventricular output maintains pulmonary microvascular pressure below
      levels required for edema development.

PMID- 7649899
TI  - Circadian rhythm of cortisol confounds cortisol responses to exercise:
      implications for future research.
AB  - To investigate whether measurements of cortisol responses to exercise are
      confounded by neglect of the hormone's circadian rhythm, we measured the serum
      and salivary cortisol responses of eight women to 40 min of 70% maximal oxygen
      consumption treadmill exercise beginning at 0800 and 2000. Responses were
      calculated relative to the usually employed preexercise concentrations and also
      to concentrations at the same times of another day while subjects were at rest.
      Compared with areas under response curves (AUCs) calculated relative to their
      circadian baselines, AUCs for serum and salivary cortisol calculated by reference
      to preexercise concentrations were underestimated (serum, P < 0.001; salivary, P
      < 0.01) by 93 and 84% in the morning and by 37 and 35% in the evening,
      respectively. Calculated by the usual preexercise baseline method, rises in serum
      and salivary cortisol were similarly underestimated. More accurately calculated
      relative to their circadian baselines, serum and salivary cortisol AUCs were
      similar (P = 0.63 and P = 0.37, respectively) in the morning and evening, as were
      their rises (P = 0.23 and P = 0.70, respectively). In future investigations of
      the existence and magnitude of cortisol responses, those responses must be
      calculated relative to the hormone's circadian baseline.

PMID- 7649900
TI  - Metabolic end products inhibit sarcoplasmic reticulum Ca2+ release and
      [3H]ryanodine binding.
AB  - Sarcoplasmic reticulum (SR) Ca2+ release channel function is modified by ligands
      (Mg2+, Ca2+, ATP, and H+) that are generated during a bout of exercise. We have
      examined the effects of changing intracellular metabolites on Ca2+ release,
      [3H]ryanodine binding, and single-Ca2+ release channel activity of SR isolated
      from white rabbit skeletal muscle. Increasing Mg2+ (from 0 to 4 mM) and
      decreasing pH (7.1-6.5) inhibited SR Ca2+ release and [3H]-ryanodine binding. In
      addition, increasing lactate concentrations from 2 to 20 mM inhibited
      [3H]ryanodine binding to SR vesicles, inhibited SR Ca2+ release, and decreased
      the single-channel open probability. These findings suggest that intracellular
      modifications that disrupt excitation-contraction coupling and decrease Ca2+
      transients will promote a decline in tension development and contribute to muscle
      fatigue. In addition, we show that hydrogen peroxide induces Ca2+ release and
      increases [3H]ryanodine binding to its receptor, suggesting that reactive oxygen
      species produced during exercise may compromise muscle function by altering the
      normal gating of the SR Ca2+ release channel.

PMID- 7649901
TI  - Adaptations of rat lateral gastrocnemius motor units in response to voluntary
      running.
AB  - This study investigated the effects of 12 wk of voluntary wheel running on motor
      units from rat lateral gastrocnemius. Motor units were isolated via ventral root
      splitting (L5) from active or sedentary rats and were classified into slow, fast
      fatigue-resistant, and fast-fatigable (FF) units. An overall increase in mean
      motor unit tetanic tension (35%) was accompanied by a decrease in mean motor unit
      fatigue resistance (-10%). These adaptations were localized in the fast unit
      population but varied among fast motor unit subtypes. The overall increase in
      tetanic force was due primarily to increases in fast-fatigue-resistant units
      (300%), whereas changes in fatigue resistance (-43%) were confined to FF units.
      However, the changes seen with activity may have been partly obscured by
      classifying fast motor units based on fatigability, since a significant increase
      in tetanic force accompanied by a decreased twitch one-half relaxation time was
      apparent in units falling in the midrange of the tetanic force continuum and
      included a number of FF units. These data provide direct demonstration of
      nonuniform motor unit adaptations subsequent to increases in normal functional
      activity.

PMID- 7649902
TI  - Respiratory and cardiovascular responses to increased and decreased carotid sinus
      pressure in sleeping dogs.
AB  - The purpose of this study was to determine the effects of changing blood pressure
      in the carotid sinus (Pcs) on ventilatory output during wakefulness and non-rapid
      eye-movement sleep in unanesthetized dogs. Eight dogs were chronically
      instrumented so that ventilation, heart rate, and blood pressure could be
      measured while pressure in the isolated carotid sinus was rapidly changed by
      means of an extracorporeal perfusion circuit. Raising Pcs 35-75 mmHg consistently
      reduced ventilation 15-40% in a dose-response fashion, with little or no further
      diminution in minute ventilation as Pcs was further increased > 75 mmHg above
      control level. This decrease in minute ventilation was immediate, due primarily
      to a decrease in tidal volume, and was sustained over the 20-s period of elevated
      Pcs. Increases in Pcs also caused immediate sustained reductions in systemic
      blood pressure and heart rate, both of which also fell in a dose-dependent
      fashion. The ventilatory and systemic cardiovascular responses to increased Pcs
      were the same during wakefulness and non-rapid-eye-movement sleep. Decreasing Pcs
      40-80 mmHg caused a sudden carotid chemoreceptor-mediated hyperpnea that was
      eliminated by hyperoxia. We conclude that increasing Pcs causes a reflex
      inhibition of ventilation and that this reflex may play a role in sleep
      disordered breathing.

PMID- 7649903
TI  - Effects of raising carotid sinus pressure on upper airway resistance and EEG
      frequency in sleeping dogs.
AB  - The purpose of this study was to determine whether acutely raising carotid sinus
      pressure (Pcs) causes changes in upper airway resistance and/or
      electroencephalographic (EEG) frequency during wakefulness and non-rapid-eye
      movement (NREM) sleep. Five dogs were chronically instrumented so that breathing,
      tracheal pressure, mouth pressure, EEG, and electrooculogram could be measured
      while pressure in the vascularly isolated carotid sinus was rapidly increased
      between 40 and 150 mmHg via an extracorporeal perfusion circuit. Dogs were
      studied during both wakefulness and NREM sleep. Multiple trials of increased Pcs
      were conducted in each dog. We observed that increasing Pcs 40-150 mmHg caused
      not only a reflex cardiovascular response but also a 15-40% decrease in minute
      ventilation. Raising Pcs caused no physiologically significant changes in upper
      airway resistance over the range of airway pressures and flow rates encountered
      during inspiration and expiration. Even dogs that demonstrated moderate to
      substantial sleep-induced increases in airway resistance did not consistently
      increase resistance during superimposed baroreceptor stimulation. Small increases
      in airway resistance were sometimes observed during baroreceptor stimulation, but
      this was not a consistent finding. Acute increases in Pcs did not cause
      measurable changes in EEG frequency during wakefulness or NREM sleep. We conclude
      that acute stimulation of the carotid sinus baroreceptors does not cause
      physiologically meaningful changes in upper airway resistance or EEG activity in
      awake or sleeping dogs.

PMID- 7649904
TI  - Contribution of diaphragmatic power output to exercise-induced diaphragm fatigue.
AB  - In nine normal humans we compared the effects on diaphragm fatigue of whole body
      exercise to exhaustion (86-93% of maximal O2 uptake for 13.2 +/- 2.0 min) to
      voluntary increases in the tidal integral of transdiaphragmatic pressure
      (integral of Pdi) while at rest at the same magnitude and frequency and for the
      same duration as those during exercise. After the endurance exercise, we found a
      consistent and significant fall (-26 +/- 2.9%, range -19.2 to -41.0%) in the Pdi
      response to supramaximal bilateral phrenic nerve stimulation at all stimulation
      frequencies (1, 10, and 20 Hz). Integral of Pdi.fB (where fB is breathing
      frequency) achieved during exercise averaged 509 +/- 81.0 cmH2O/min (range 304.0
      957.0 cmH2O/min). At rest, voluntary production of integral of Pdi.fB, which was
      < 550-600 cmH2O/min (approximately 4 times the resting eupenic integral of Pdi.fB
      or 60-70% of Pdi capacity), did not result in significant diaphragmatic fatigue,
      whereas sustained voluntary production of integral of Pdi.fB in excess of these
      threshold values usually did result in significant fatigue. Thus, with few
      exceptions (5 of 23 tests) the ventilatory requirements of whole body endurance
      exercise demanded a level of integral of Pdi.fB that, by itself, was not
      fatiguing. The rested first dorsal interosseous muscle showed no fatigue in
      response to supramaximal ulnar nerve stimulation after whole body exercise. We
      postulate that the effects of locomotor muscle activity, such as competition for
      blood flow distribution and/or extracellular fluid acidosis, in conjunction with
      a contracting diaphragm account for most of the exercise-induced diaphragm
      fatigue.

PMID- 7649905
TI  - Thermoregulatory responses of rats acclimated to heat given daily at a fixed
      time.
AB  - Body core temperature of rats acclimated to heat given daily at a fixed time
      falls during the previous heat exposure time. In the present study,
      thermoregulatory responses of heat-acclimated rats were examined during the
      specific period. Heat-acclimated rats were subjected to an ambient temperature of
      32 degrees C for approximately 5 h in the first half or last half of the dark
      phase for 14 days while control rats were kept at 24 degrees C. Then the rats
      were placed in a direct calorimeter and were warmed for 30 min with an
      intraperitoneal electric heater. Measurements were made twice in the first and
      last halves of the dark phase. Body warming significantly increased body core
      temperature in all rats. In the heat-acclimated rats, heat production (M) was
      significantly depressed during the previous heat exposure time but not during the
      other period. Body warming had little effect on M in the control rats during
      either period. The results suggest that rats acclimated to heat given at a fixed
      time daily respond to an acute heat load with a pronounced reduction of M.
      However, such a response was observed only during the period when the rats had
      been previously exposed to heat.

PMID- 7649906
TI  - Human fiber size and enzymatic properties after 5 and 11 days of spaceflight.
AB  - Biopsies from the vastus lateralis muscle were obtained from three astronauts
      before and after two 5-day flights and from five astronauts before and after one
      11-day flight (space shuttle flights: STS-32, -33, and -34). Muscle fibers from
      two separate samples from each biopsy were classified as type I and II or as type
      I, IIA, and IIB by using qualitative myofibrillar adenosinetriphosphatase
      (ATPase) staining. Cross-sectional area (CSA), number of capillaries per fiber,
      and the activities of succinate dehydrogenase (SDH), alpha-glycerophosphate
      dehydrogenase (GPD), and myofibrillar ATPase were determined from one sample of
      fibers of each myofibrillar ATPase type. Postflight biopsies had 6-8% fewer type
      I fibers than preflight. Mean fiber CSAs were 16-36% smaller after the 11-day
      flight with the relative effect being type IIB > IIA > I. Mean fiber CSAs were 11
      and 24% smaller in type I and II fibers after 5 days of flight. Myofibrillar
      ATPase activities increased in type II but not in type I fibers after flight,
      whereas SDH activity was unaffected in either fast or slow fibers. GPD activity
      in type I fibers was approximately 80% higher (P > 0.05) postflight compared with
      preflight. Myofibrillar ATPase/SDH ratios in type II fibers were higher after
      than before flight, suggesting that some fast fibers were more susceptible to
      fatigue after flight. The GPD/SDH ratios were elevated in some type I fibers
      after spaceflight. The number of capillaries per fiber was 24% lower after than
      before flight, whereas the number of capillaries per unit CSA of muscle tissue
      was unchanged. These data suggest that adaptations in the size, metabolic
      properties, and vascularity of muscle fibers can occur rapidly in the space
      environment. These adaptations were qualitatively similar to those observed in
      animals after actual or simulated spaceflight conditions for short periods.

PMID- 7649907
TI  - Myosin heavy chain isoforms of human muscle after short-term spaceflight.
AB  - The influence of microgravity on the myosin phenotype of skeletal muscle fibers
      in the vastus lateralis of eight crew members was studied before and after 5-day
      (n = 3) and 11-day (n = 5) spaceflights (space shuttle flights: STS-32, -33 and 
      34). Single-fiber electrophoresis analyses showed that the proportion of fibers
      expressing only slow (type I) myosin heavy chain (MHC) in the vastus lateralis
      was significantly lower after than before 11 days of spaceflight. Although the
      family of type II MHC isoforms was elevated post- compared with preflight, the
      distribution among the isoforms of type II MHC was not statistically different.
      Based on monoclonal and polyclonal antibodies specific for three adult MHC
      isoforms and single-fiber electrophoresis, approximately 3% of the fibers
      analyzed coexpressed all three adult MHC isoforms. The results from
      immunohistochemical staining with two different sets of antibodies indicate a
      reduction in the percentage of fibers expressing type I MHC as a result of
      spaceflight. The mean difference, however, was significant only when the fibers
      were categorized simply as type I or II. These changes appeared to be highly
      individualized among the astronauts. These results suggest that a rapid change in
      MHC isoform expression can occur in some muscle fibers after a relatively brief
      exposure to spaceflight.

PMID- 7649908
TI  - Site of pulmonary vasodilation by inhaled nitric oxide in the perfused lung.
AB  - To determine the site of inhaled nitric oxide (NO)-induced pulmonary
      vasodilation, a double vascular occlusion technique was used with rabbit lungs
      ventilated and perfused at 20 ml/min with Krebs solution containing 3% dextran
      and 30 microM indomethacin. Inhaled NO (120 ppm for 3 min) reduced pulmonary
      vasoconstriction produced by U-46619 infusion (0.5-1.2 nmol/min), significantly
      decreasing total resistance (RT) [1,080 +/- 51 (SE) vs. 1,545 +/- 109 mmHg.l
      1.min; P < 0.01]. Acetylcholine infusion (ACh; 2-5 nmol/min) and nitroglycerin
      (NTG; 0.35 mumol) likewise decreased RT. Arterial resistance (Ra) was also
      significantly less with inhaled NO, ACh, and NTG compared with U-46619 alone.
      Venous resistance (Rv), however, was unchanged. When the direction of perfusion
      was reversed in the lung, inhaled NO, ACh, and NTG significantly decreased RT
      compared with U-46619 alone, and Rv was also reduced by all three agents. After
      electrolysis-induced acute lung injury, inhaled NO significantly reduced both RT
      and Ra compared with U-46619 alone, whereas Rv was unaffected. Our results
      demonstrate that inhaled NO gas affects primarily the arterial (precapillary)
      component of the pulmonary circulation but, under conditions of extreme venous
      constriction, may dilate the postcapillary component as well.

PMID- 7649909
TI  - Effects of acute and chronic exercise on skeletal muscle glucose transport in
      aged rats.
AB  - The purpose of this study was to investigate the effects of acute and chronic
      exercise on skeletal muscle glucose transport in aged rats by using an isolated
      sarcolemmal membrane preparation. In 24-mo-old female Fischer 344 rats, a maximum
      dose of insulin increased glucose transport from 43 +/- 6 to 82 +/- 6 pmol.mg
      protein-1.15 s-1. A 45-min bout of exhaustive treadmill running increased glucose
      transport to the same maximum level (88 +/- 5 pmol.mg protein-1.15 s-1). Eight
      weeks of progressive exercise training resulted in a 65% increase in succinic
      dehydrogenase activity in hindlimb muscles and a 55% increase in total cellular
      GLUT-4 content. Despite these biochemical adaptations, there was no change in
      either basal or maximum insulin-stimulated glucose transport between control (43
      +/- 6 and 82 +/- 6 pmol.mg protein-1.15 s-1, respectively) and trained (42 +/- 2
      and 82 +/- 8 pmol.mg protein-1.15 s-1, respectively) animals. When hindlimb
      muscle succinate dehydrogenase activity and GLUT-4 content were compared for both
      the combined sedentary and trained groups, a significant correlation (r = 0.68)
      was obtained. This study demonstrates that the skeletal muscle glucose transport
      system of 24-mo-old rats is fully stimulated by acute exercise and that, although
      GLUT-4 levels are increased in aged animals after exercise training, this does
      not result in an enhancement of maximal insulin-stimulated glucose transport.
      Thus increases in GLUT-4 are not sufficient to improve muscle insulin
      responsiveness with training.

PMID- 7649910
TI  - Effects of oxygenation and hypercapnia on diaphragmatic function and central
      drive during respiratory failure.
AB  - The effects of oxygenation and hypercapnia on diaphragmatic function and central
      drives were assessed during the development of respiratory failure in
      anesthetized unbound spontaneously breathing rabbits. Oxygenation significantly
      altered endurance times, whereas hypercapnia had no effect. Isolated high
      frequency contractile fatigue of the diaphragm was found in hyperoxic animals;
      all other animals had no evidence of contractile fatigue. Oxygenation and
      hypercapnia did not significantly alter the response of breathing frequency or
      duty cycle to loading. In all animals, there was a falloff in the intensity of
      central drive before apnea, with intensity of central drive remaining submaximal
      throughout loading. Oxygenation significantly altered the time and/or load at
      which drive intensity fell off, although critical blood gas levels were not
      associated with the falloff in intensity. We conclude that oxygenation influences
      the development of respiratory failure during inspiratory loading but does not
      directly explain the alterations is central drive. On the other hand, hypercapnia
      has no direct effect on respiratory muscle function or central drives during
      loading to respiratory failure. When the effects of hypoxemia are obviated by
      hyperoxia, high-frequency contractile fatigue may occur.

PMID- 7649911
TI  - Anaerobic threshold and respiratory compensation in pregnant women.
AB  - In an effort to explore why CO2 output (VCO2) at peak exercise is lower during
      pregnancy than postpartum despite little change in the peak O2 uptake (VO2), we
      determined the VCO2/VO2 relationship during rapidly incremental exercise and
      estimated the anaerobic threshold (AT) and the respiratory compensation (RC)
      point. We measured heart rate, VO2, VCO2, and minute ventilation (VE) at rest and
      during cycle exercise tests with rapidly increasing exercise intensities until
      maximal effort in 33 volunteers at 16-, 25-, and 35-wk gestation and postpartum.
      Through modification of the V-slope method, we estimated the AT and RC point for
      each test by nonlinear regression analysis in a three-dimensional space (defined
      by VE, VO2, and VCO2) for a line assumed to have two breakpoints; we found a good
      fit for all tests. The AT and RC points were found at exercise intensities of
      approximately 50 and 80% peak VO2, respectively, with no significant differences
      between test periods. VE was significantly higher during pregnancy than during
      postpartum at rest and throughout incremental exercise. A lower peak VCO2
      relative to peak VO2 during pregnancy compared with postpartum was reflected by a
      more shallow slope of VCO2 vs. VO2 above the AT point. This suggests that during
      pregnancy the buffering of lactic acid is reduced.

PMID- 7649912
TI  - Continuous measurement of ATP by 31P-NMR in term human dually perfused placenta
      in vitro: response to ischemia.
AB  - ATP was examined in dually perfused term human placentas by using 31P-nuclear
      magnetic resonance (NMR) spectroscopy. 31P-NMR spectra were acquired every 30 min
      starting approximately 30 min after establishing fetal and maternal perfusions,
      and maternal perfusate samples were obtained to monitor glucose utilization,
      lactate production, and human chorionic gonadotropin (hCG) and human placental
      lactogen (hPL) release. In continuous-perfusion experiments, placentas were
      perfused as long as 10 h. ATP increased and Pi fell after initiation of
      perfusion. Fetal volume loss was < 2 ml/h, and constant production of hCG, hPL,
      and lactate as well as constant utilization of glucose were observed. In
      additional experiments, ischemia was produced by halting maternal and fetal
      perfusion pumps after a 2-h control period. After 2, 3, or 4 h of ischemia, ATP
      decreased 46 +/- 17, 51 +/- 5, and 85% of control, respectively. When perfusion
      was reinitiated, ATP increased and was maintained for the duration of the
      experiment (an additional 2 h). Recovery of ATP after reperfusion was not
      paralleled by recovery in glucose utilization, lactate production, or hPL and hCG
      release. However, during the reperfusion period, fetal pressure was < 70 mmHg and
      fetal volume loss was < 2 ml/h. These investigations suggest that the dually
      perfused human placental lobule can maintain ATP for > or = 10 h. Although the
      perfused human placenta recovers ATP and maintains fetal perfusion volume after
      ischemia lasting up to 4 h, utilization of glucose, production of lactate, and
      production and release of hCG and hPL are impaired.

PMID- 7649913
TI  - Pulmonary function alterations after 3 wk of exposure to hypobaria and/or hypoxia
      in growing rats.
AB  - We studied lung growth in rats between 4 and 7 wk of age under different
      conditions. There were five groups, seven animals in each: 1) general controls
      (ambient pressure and room air, food ad libitum); 2) hypobaric normoxic
      [barometric pressure (PB) 410 mmHg, PO2 153 Torr]; 3) normobaric hypoxic (ambient
      pressure, PO2 80 Torr); 4) hypobaric hypoxic (PB 410 mmHg, PO2 80 Torr); and 5)
      weight-matched controls to hypobaric hypoxic. Residual volume, functional
      residual capacity, vital capacity, and total lung capacity grew 10-20% more in
      both hypoxic groups than in weight-matched and general controls. Expiratory flow
      rates corrected for forced vital capacity decreased, and specific airway
      resistance increased significantly. In addition, the ratio of forced expiratory
      volume in 0.1 s to %forced vital capacity, peak expiratory flow rate, and forced
      maximal midexpiratory flow were also lower in normobaric hypoxic animals compared
      with weight-matched controls. Above a transpulmonary pressure of 6 cmH2O, flows
      were reduced in both hypoxic groups. No differences were observed between
      hypobaric normoxic and general control groups for lung volume and lung function.
      In weight-matched animals, total lung capacity decreased but lung function
      remained unchanged. We conclude that accelerated lung growth in hypobaric hypoxia
      and normobaric hypoxia is dysanaptic. Lung growth in hypobaric hypoxia is
      primarily induced by low oxygen, but differences between hypobaric hypoxia and
      normobaric hypoxia suggest a beneficial effect of low pressure.

PMID- 7649914
TI  - Effects of isoproterenol on the cardiovascular system of fetal sheep exposed to
      long-term high-altitude hypoxemia.
AB  - We exposed fetuses to high-altitude (3,820 m) hypoxemia from 30 to 130 days
      gestation, when we measured fetal heart rate, right and left ventricular outputs
      with electromagnetic flow probes, and arterial blood pressure during an
      isoproterenol dose-response infusion. We also measured the distribution of
      cardiac output with radiolabeled microspheres during the maximal isoproterenol
      dose. Baseline fetal arterial blood pressure was higher in long-term hypoxemic
      fetuses (50.1 +/- 1.3 vs. 43.4 +/- 1.0 mmHg) but fell during the isoproterenol
      infusion to 41.3 +/- 1.4 and 37.5 +/- 1.4 mmHg, respectively, at the highest
      dose. Heart rate was the same in both groups and did not differ during
      isoproterenol infusion. Baseline fetal cardiac output was lower in the hypoxemic
      group (339 +/- 18 vs. 436 +/- 19 ml.min-1.kg-1) due mainly to a reduction in
      right ventricular output. During the isoproterenol infusion, right ventricular
      output increased to the same extent in both hypoxemic and normoxic fetuses
      (approximately 35%); however, left ventricular output increased only
      approximately 15% in the hypoxemic group compared with approximately 40% in the
      normoxic group. The percent change in individual organ blood flows during
      isoproterenol infusion in the hypoxemic groups was not significantly different
      from the normoxic group. All of the mechanisms that might be responsible for the
      differential response of the fetal left and right ventricles to long-term hypoxia
      are not understood and need further exploration.

PMID- 7649915
TI  - Interaction of surfactant mixtures with reactive oxygen and nitrogen species.
AB  - Increased concentrations of partially reduced oxygen and nitrogen reactive
      species damage the alveolar epithelium and either cause or exacerbate surfactant
      deficiency. For this reason, there is a quest to identify surfactant replacement
      mixtures, which in addition to repleting depleted surfactant stores can also
      reduce the steady-state concentrations of reactive species in the alveolar space.
      Herein, we evaluated the ability of natural lung surfactant (NLS) and two
      mixtures (Exosurf and Survanta) used clinically for the correction of surfactant
      deficiency to scavenge hydroxyl radical-type species (.OH), generated either by
      the decomposition of peroxynitrite or by Fenton reagents (FeCl3 + H2O2). Exosurf
      or Survanta decreased .OH only when present at high lipid concentrations (6.5
      mM). On the other hand, 40 microM of NLS decreased .OH concentrations from 75 +/-
      2 to 53 +/- 2 microM (P < 0.05), most likely because of the interaction of .OH
      with protein sulfhydryl groups. Similarly, 40 microM of NLS incubated with a
      bolus of H2O2 (400 microM) decreased the H2O2 concentration in the supernatant by
      approximately 50%, due to the presence of catalase-type activity. In contrast to
      NLS, neither Exosurf nor Survanta scavenged H2O2, even when present at millimolar
      lipid concentrations. We concluded that Exosurf and Survanta contain limited
      antioxidant activity compared with NLS.

PMID- 7649916
TI  - Pharyngeal narrowing/occlusion during central sleep apnea.
AB  - We hypothesized that subatmospheric intraluminal pressure is not required for
      pharyngeal occlusion during sleep. Six normal subjects and six subjects with
      sleep apnea or hypopnea (SAH) were studied during non-rapid-eye-movement sleep.
      Pharyngeal patency was determined by using fiber-optic nasopharyngoscopy during
      spontaneous central sleep apnea (n = 4) and induced hypocapnic central apnea via
      nasal mechanical ventilation (n = 10). Complete pharyngeal occlusion occurred in
      146 of 160 spontaneously occurring central apneas in patients with central sleep
      apnea syndrome. During induced hypocapnic central apnea, gradual progressive
      pharyngeal narrowing occurred. More pronounced narrowing was noted at the
      velopharynx relative to the oropharynx and in subjects with SAH relative to
      normals. Complete pharyngeal occlusion frequently occurred in subjects with SAH
      (31 of 44 apneas) but rarely occurred in normals (3 of 25 apneas). Resumption of
      inspiratory effort was associated with persistent narrowing or complete occlusion
      unless electroencephalogram signs of arousal were noted. Thus pharyngeal cross
      sectional area is reduced during central apnea in the absence of inspiratory
      effort. Velopharyngeal narrowing consistently occurs during induced hypocapnic
      central apnea even in normal subjects. Complete pharyngeal occlusion occurs
      during spontaneous or induced central apnea in patients with SAH. We conclude
      that subatmospheric intraluminal pressure is not required for pharyngeal
      occlusion to occur. Pharyngeal narrowing or occlusion during central apnea may be
      due to passive collapse or active constriction.

PMID- 7649917
TI  - Artificial surfactant attenuates hyperoxic lung injury in primates. I. Physiology
      and biochemistry.
AB  - Prolonged exposure to O2 causes diffuse alveolar damage and surfactant
      dysfunction that contribute to the pathophysiology of hyperoxic lung injury. We
      hypothesized that exogenous surfactant would improve lung function during O2
      exposure in primates. Sixteen healthy male baboons (10-15 kg) were anesthetized
      and mechanically ventilated for 96 h. The animals received either 100% O2 (n = 6)
      or 100% O2 plus aerosolized artificial surfactant (Exosurf; n = 5). A third group
      of animals (n = 5) was ventilated with an inspired fraction of O2 of 0.21 to
      control for the effects of sedation and mechanical ventilation. Hemodynamic
      parameters were obtained every 12 h, and ventilation-perfusion distribution
      (VA/Q) was measured daily using a multiple inert-gas elimination technique.
      Positive end-expiratory pressure was kept at 2.5 cmH2O and was intermittently
      raised to 10 cmH2O for 30 min to obtain additional measurements of VA/Q. After
      the experiments, lungs were obtained for biochemical and histological assessment
      of injury. O2 exposures altered hemodynamics, progressively worsened VA/Q,
      altered lung phospholipid composition, and produced severe lung edema. Artificial
      surfactant therapy significantly increased disaturated phosphatidylcholine in
      lavage fluid and improved intrapulmonary shunt, arterial PO2, and lung edema.
      Surfactant also enhanced the shunt-reducing effect of positive end-expiratory
      pressure. We conclude that an aerosolized protein-free surfactant decreased the
      progression of pulmonary O2 toxicity in baboons.

PMID- 7649918
TI  - Artificial surfactant attenuates hyperoxic lung injury in primates. II.
      Morphometric analysis.
AB  - Diffuse lung injury from hyperoxia is accompanied by low compliance and hypoxemia
      with disruption of endothelial and alveolar epithelial cell layers. Because both
      function and content of surfactant in diffuse lung injury decrease in animals and
      in humans, changes in the extent of injury during continuous hyperoxia were
      evaluated after treatments with a protein-free surfactant in primates. Ten
      baboons were ventilated with 100% O2 for 96 h and five were intermittently given
      an aerosol of an artificial surfactant (Exosurf). Physiological and biochemical
      measurements of the effects of the surfactant treatment are presented in a
      companion paper (Y.-C. T. Huang, A. C. Sane, S. G. Simonson, T. A. Fawcett, R. E.
      Moon, P. J. Fracica, M. G. Menache, C. A. Piantadosi, and S. L. Young. J. Appl.
      Physiol. 78: 1823-1829, 1995.) After O2 exposures, lungs were fixed and processed
      for electron microscopy. The cellular responses to O2 included epithelial and
      endothelial cell injuries, interstitial edema, and inflammation. Morphometry was
      used to quantitate changes in lungs of animals treated with the artificial
      surfactant during O2 exposure and to compare them with the untreated animals. The
      surfactant decreased neutrophil accumulation, increased fibroblast proliferation,
      and decreased changes in the volume of type I epithelial cells. Surfactant
      treated animals also demonstrated better preservation of endothelial cell
      integrity. These responses indicate ameliorating effects of the surfactant on the
      pulmonary response to hyperoxia, including protection against epithelial and
      endothelial cell destruction. Significant interstitial inflammation and
      fibroblast proliferation remained, however, in surfactant-treated lungs exposed
      to continuous hyperoxia.

PMID- 7649919
TI  - Increased prostacyclin production during exercise in untrained and trained men:
      effect of low-dose aspirin.
AB  - The influence of a submaximal exercise on urinary 2,3-dinor-6-ketoprostaglandin
      F1 alpha (2,3-dinor-6-keto-PGF1 alpha), 2,3-dinor-thromboxane B2 (2,3-dinor
      TxB2), and prostaglandin E2 excretion and on platelet aggregation was compared in
      untrained and trained subjects before and after low-dose aspirin administration
      (50 mg/day, 7 days). 2,3-Dinor-TxB2 excretion was significantly higher in the
      athletes at rest (P < 0.05). Submaximal exercise selectively increased 2,3-dinor
      6-keto-PGF1 alpha excretion without affecting 2,3-dinor-TxB2 or prostaglandin E2
      excretion rates or platelet aggregation. Low-dose aspirin inhibited platelet
      aggregation and 2,3-dinor-TxB2 excretion but reduced 2,3-dinor-6-keto-PGF1 alpha
      by only 24% in the untrained and by 51% in the trained subjects (P < 0.05). After
      low-dose aspirin administration, the selective stimulatory effect of submaximal
      exercise on urinary 2,3-dinor-6-keto-PGF1 alpha excretion was even more
      pronounced than before. The ratio of 2,3-dinor-6-keto-PGF1 alpha to 2,3-dinor
      TxB2 was increased by exercise; this effect was significantly enhanced by low
      dose aspirin (P < 0.05). Our results suggest that the stimulatory effect of
      submaximal exercise on prostacyclin production is mostly due to an activation of
      prostacyclin synthesis from endogenous precursors rather than the result of an
      enhanced endoperoxide shift from activated platelets to the endothelium. This
      effect is potentiated by low-dose aspirin pretreatment, indicating that 50 mg/day
      of aspirin do not impair exercise-induced endothelial prostacyclin production.

PMID- 7649920
TI  - Gradient of fatty acids from blood plasma to skeletal muscle in dogs.
AB  - In anesthetized dogs, the amount of fatty acyl moieties in the fatty acid,
      triacylglycerol, and phospholipid fractions of arterial blood and biceps femoris
      muscle has been determined to delineate the presence of a fatty acid gradient
      from blood to skeletal muscle tissue, if any. The content of fatty acids in
      biceps femoris muscle was found to be very low (approximately 0.1% of total
      amount of unesterified and esterified fatty acyl moieties in the tissue sample).
      The ratio of the content of fatty acids (nmol/ml) in arterial plasma and the
      tissue level of fatty acids (nmol/g wet weight) was approximately 17. This
      finding supports the notion that a fatty acid gradient from the vascular
      compartment to the skeletal muscle fibers might be one of the driving forces of
      net extraction of fatty acids by skeletal muscle.

PMID- 7649921
TI  - Allergen-induced hyperresponsiveness to bradykinin is more pronounced than that
      to methacholine.
AB  - Bradykinin reduces airflow in asthmatic patients via indirect mechanism(s),
      possibly involving sensory nerve stimulation and increased vascular permeability.
      We hypothesized that allergen inhalation, which affects reactivity of nerves and
      vessels, would differentially alter reactivity to bradykinin and the smooth
      muscle spasmogen methacholine. We compared reactivity to methacholine and
      bradykinin 1, 2, 4, 7, 11, and 14 days after allergen provocation in 12 atopic
      asthmatic patients with stable baseline reactivity to bradykinin. Maximal
      allergen-induced shifts from baseline in reactivity were 0.73 +/- 0.12 log unit
      for bradykinin compared with 0.27 +/- 0.13 log units for methacholine (P =
      0.0005). Nine subjects showed significant increases in bradykinin reactivity,
      with four subjects increasing reactivity by > 1 log unit. Moreover, the maximal
      mean change in bradykinin reactivity occurred 2 days postallergen. Thus, allergen
      induced changes in reactivity to bradykinin and methacholine differ in magnitude
      and time course. Bradykinin inhalational challenge provides a sensitive index of
      the airway's response to allergen.

PMID- 7649922
TI  - Skeletal muscle phosphofructokinase activity examined under physiological
      conditions in vitro.
AB  - The in vitro activity of skeletal muscle phosphofructokinase (PFK) was determined
      over the full physiological range of citrate concentrations. Enzyme aggregation
      was enhanced with a crowding agent, as the regulatory properties of PFK are
      altered with dilution. Cuvette conditions simulated concentrations of effectors
      and substrates during rest, moderate aerobic exercise, and intense aerobic
      exercise in human skeletal muscle. Citrate inhibition was not eliminated with
      enhanced enzyme aggregation, but activity was improved at all citrate
      concentrations. Maximal PFK activity with no citrate present was 0.27 +/- 0.01
      mumol.min-1.mg-1 protein with resting effectors and 1.64 +/- 0.07 and 7.15 +/-
      0.52 mumol.min-1.mg-1 protein with moderate aerobic and intense aerobic effector
      levels, respectively. Under resting conditions, PFK activity decreased to 49% of
      maximal when citrate was increased from 0 to 0.15 mM and only a small further
      inhibition to 43% occurred at 0.5 mM. Citrate was a less potent inhibitor under
      both exercise conditions with the sharpest decline to 72-77% of maximal activity
      at 0.15 mM followed by a slower decline to 65-70 and 53% activity at 0.25 and 0.5
      mM citrate, respectively. The present in vitro measurements predict that
      alterations in citrate around concentrations normally reported in resting and
      exercising muscle would have little effect on flux through PFK. Therefore, the
      generally accepted concept that citrate is a potent inhibitor of PFK in all
      physiological situations has been exaggerated.

PMID- 7649923
TI  - Differential effect of ventrolateral medullary cooling on respiratory muscles of
      goats.
AB  - The objective was to determine whether there is an inhomogeneous response of
      respiratory muscles during cooling-induced ventrolateral medullary (VLM) neuronal
      dysfunction in anesthetized and awake goats. Thermodes for cooling were
      chronically implanted on all or portions of rostral, intermediate, and caudal
      areas of the VLM of 16 adult goats. Electromyograms (EMGs) were obtained from
      chronically implanted wires in the diaphragm (di), transversus abdominis (TA),
      and triangularis sterni (TS) muscles. During some periods of cooling in 9 of 16
      anesthetized airway-intubated goats, complete cessation of EMGdi coincided with a
      reduced yet sustained inspiratory flow. In six awake tracheotomized goats, VLM
      cooling decreased (P < 0.05) EMGdi duration and minute activity more than
      inspiratory duration and minute ventilation. Cooling thus decreased activation of
      the diaphragm more than activation of other respiratory muscles. On the other
      hand, during VLM cooling in 3 of 10 airway-intact awake goats, cessation of
      inspiratory flow coincided with sustained EMGdi, suggesting that cooling
      decreased stimulation of the upper airway muscles more than stimulation of the
      diaphragm. Finally, VLM cooling in a majority of goats decreased EMGTA and EMGTS
      more than EMGdi. We conclude that VLM neuronal dysfunction has a differential
      effect on respiratory muscles of adult anesthetized and awake goats.

PMID- 7649924
TI  - Maximal exercise performance in chronic hypoxia and acute normoxia in high
      altitude natives.
AB  - Maximal O2 uptake (VO2max) was determined on a bicycle ergometer in chronic
      hypoxia (CH) and during acute exposure to normoxia (AN) in 50 healthy young men
      who were born and had lived at 3,600 m altitude (La Paz, Bolivia). VO2max was
      significantly improved (approximately 8%) by AN. However, the difference in
      VO2max measured in CH and AN (delta VO2max) was lower than that reported in sea
      level natives (SN) who exercised in chronic normoxia and acute hypoxia. It is
      shown that high-altitude natives (HN) and SN have a similar VO2max in normoxia,
      but highlanders can attain a greater VO2max when O2 availability is reduced by
      altitude exposure. In addition, in HN, the higher the subject's VO2max in
      hypoxia, the smaller his delta VO2max. These results contrast with the data
      obtained in 14 lowlanders acclimatized to high altitude who showed that their
      delta VO2max was positively related to their VO2max in hypoxia, as previously
      reported in SN who exercised in acute hypoxia (A. J. Young, A. Cymerman, and R.
      L. Burse. Eur. J. Appl. Physiol. Occup. Physiol. 54: 12-15, 1985). Furthermore,
      arterial O2 saturation of HN behaved differently from acclimatized lowland
      natives, inasmuch as it fell less during exercise both in CH and AN. HN with high
      aerobic capacity display a lower exercise ventilation and a reduced arterial
      saturation, which could explain their inability to improve VO2max with
      normoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7649925
TI  - Effect of hypoxia on intracellular pH of glomus cells cultured from cat and rat
      carotid bodies.
AB  - To test the hypothesis that hypoxia may induce cellular acidification during
      chemotransduction in the carotid body, we compared the effects of hypoxia and of
      extracellular acidosis on intracellular pH (pHi) of glomus cells cultured from
      rat and cat carotid bodies. The cells were prepared and cultured for 2-7 days.
      The plated cells were loaded with a pH-sensitive fluorescent probe, SNARF-1
      acetoxymethyl ester, and were placed in a closed chamber and superfused. The
      effects of lowering PO2 and pH in the superfusion medium containing CO2-HCO3-
      buffer on the glomus cell pHi were measured at 37 degrees C. The pHi was measured
      in a single or a few isolated cells with single excitation at 540 nm and dual
      emission at 590 and 640 nm, after the exposure to different PO2 levels from 132
      to 43, 14, and 1-2 Torr for 10-12 min in the closed chamber. The resting pHi
      values were 7.263 +/- 0.008 for rat and 7.175 +/- 0.004 for cat carotid body
      glomus cells. For a decrease of PO2 from 132 Torr to 14 Torr, the change in pHi
      values, on average, for cat and rat glomus cells was 0.034 lower, and with PO2
      decrease to 1-2 Torr for the cat glomus cells, the change in pHi values was 0.051
      lower. On the other hand, when the perfusate pH values were decreased from 7.4 to
      6.9 during normoxia, the reduction of change in pHi values were 0.327 for the rat
      and 0.397 for the cat. Thus glomus cell pHi change due to low PO2 exposure was
      not significant and was not commensurate with the large increases in the
      chemosensory activity.

PMID- 7649926
TI  - Influence of spaceflight, hindlimb suspension, and venous occlusion on alpha 1
      adrenoceptors in rat vena cava.
AB  - Effects of hindlimb suspension, spaceflight, and venous occlusion were examined
      in isolated strips from rat vena cava by using both [3H]prazosin-binding and
      contraction responses evoked by norepinephrine. Sensitivity to norepinephrine was
      decreased without modification of the maximal contractile response. Furthermore,
      the high K(+)-induced contractions were not affected, suggesting that there was
      no interference with voltage-dependent Ca2+ channels. The sensitivity of the
      norepinephrine-induced contraction to prazosin was decreased, and Scatchard
      analysis of [3H]prazosin binding indicated an increase in the dissociation
      constant without variation in maximal binding capacity. A similar increase in the
      dissociation constant was obtained in control rats after pretreatment with 3
      microM norepinephrine or 0.1 microM phorbol 12,13-dibutyrate to desensitize the
      protein kinase C. This effect was completely abolished in the presence of GF
      109203X, a selective inhibitor of protein kinase C. Taken together, these data
      indicate that altered gravity conditions induce a desensitization of alpha 1B
      adrenoceptors depending on increased protein kinase C activity. This effect can
      be mimicked by venous occlusion and may be responsible for reduced contractile
      responses to norepinephrine.

PMID- 7649927
TI  - Lung tissue and airway impedances during pulmonary edema in normal range of
      breathing.
AB  - How pulmonary edema affects lung tissue and airway properties is not clear. From
      measurements of airway pressure and flow, we measured lung elastance (EL) and
      resistance (RL) in 5 anesthetized-paralyzed open-chested dogs during sinusoidal
      forcing in the frequency (f) and tidal volume (VT) ranges of normal breathing. RL
      was divided into its tissue (Rti) and airway (Raw) components from measurements
      of alveolar pressure through capsules glued to the lung surface. After induction
      of severe pulmonary edema by injection of oleic acid into the right atrium,
      forcing was repeated at the same mean airway pressure (Paw) as in control animals
      (11 cmH2O) and at a higher Paw (14 cmH2O), as would occur in closed-chested dogs
      during edema (G. M. Barnas, D. Stamenovic, and K. R. Lutchen. J. Appl. Physiol.
      73: 1040-1046, 1992). Edema increased EL, and this increase was greater at Paw =
      14 cmH2O (P < 0.05). The f dependences of EL and Rti were increased by edema (P <
      0.05), and there was a large negative dependence of EL on VT at Paw = 14 cmH2O.
      Edema increased RL (P < 0.05), but this increase depended on f, VT, and Paw. The
      increase in RL was due largely to increases in Rti at Paw = 14 cmH2O and to
      increases in Raw at Paw = 11 cmH2O. We conclude that the functional effects of
      oleic acid-induced pulmonary edema on RL are due mostly to changes in lung
      tissue.

PMID- 7649928
TI  - Direct effects of inhaled nitric oxide on canine peripheral airways.
AB  - The effects of nitric oxide on peripheral airways in vivo, and whether these
      effects occur via direct or indirect mechanisms, are unknown. We studied effects
      of inhaled nitric oxide on histamine-constricted canine peripheral airways in the
      presence or absence of atropine and an inhibitor of guanylyl cyclase, methylene
      blue. Peripheral resistance (Rp) was measured by using a wedged-bronchoscope
      technique in anesthetized dogs. A stable baseline Rp was established. Histamine
      was infused intravenously, and increasing concentrations of nitric oxide (50-500
      ppm) were delivered through the bronchoscope. In separate experiments, histamine
      was infused intravenously in the presence or absence of atropine (0.2 mg/kg iv)
      or methylene blue (20 mg/min iv). When Rp stabilized, nitric oxide (500 ppm) was
      delivered. Nitric oxide partially reversed histamine-induced bronchoconstriction
      in a dose-dependent fashion (maximum of 42 +/- 3% reduction at 500 ppm; n = 5; P
      < 0.01) that did not differ in the presence or absence of atropine. Methylene
      blue blocked the effect of nitric oxide on histamine-induced constriction (n = 6;
      P = 0.45). These findings suggest that high concentrations of nitric oxide
      produce small but significant bronchodilation of peripheral airways through a
      mechanism independent of the cholinergic neural pathway. The mechanism of action
      appears to involve activation of guanylyl cyclase.

PMID- 7649929
TI  - Immunohistochemical demonstration of four subunits of neutrophil NAD(P)H oxidase
      in type I cells of carotid body.
AB  - We demonstrate, by means of immunohistochemistry, that type I cells of human,
      guinea pig, and rat carotid bodies react with antisera raised against the
      subunits p22phox, gp91phox, p47phox, and p67phox of the NAD(P)H oxidase isolated
      from human neutrophil granulocytes. The findings support previous photometric
      studies that indicate that carotid body type I cells possess a putative oxygen
      sensor protein that is similar to the neutrophil NAD(P)H oxidase and consists of
      a hydrogen peroxide generating low-potential cytochrome b558 with cofactors
      regulating the electron transfer to oxygen.

PMID- 7649930
TI  - Control of expiratory time in conscious humans.
AB  - Combinations of 17 normal awake humans breathed mildly hyperoxic and hypercapnic
      gas mixtures via a pneumotachograph into an open circuit. Respiratory pattern was
      measured for each breath in real time by computer. Use of computer-controlled
      auditory feedback at a constant end-tidal PCO2 (PETCO2) allowed prolonged changes
      of 1) inspiratory time (TI) at constant inspired tidal volume (VTI), 2) VTI up
      and down in repeated steps at constant TI, and 3) expiratory time (TE) at
      constant VTI. The remaining variables were free to be determined by the subjects'
      automatic respiratory control mechanisms. We showed that TE changed in parallel
      with the change in TI despite constant VTI, TE did not change in response to step
      changes in VTI at constant TI, and large changes in TE had no influence on the
      subsequent TI, but VTI increased slightly as TE lengthened despite clamping. Time
      for expiratory flow (TE--end-expiratory pause) changed in parallel with TE in all
      protocols. Thus, in conscious humans, inspiratory timing has a direct influence
      on expiratory timing, independent of volume change and chemical drive, but
      expiratory timing has no influence on the inspiratory timing of the subsequent
      breath but has a small influence on volume.

PMID- 7649931
TI  - Tracheal epithelial damage alters tracer fluxes and effects of tracheal osmolaity
      in sheep in vivo.
AB  - Tracheal osmolaity affects blood flow and the flux of a tracer, technetium-99m
      labeled diethylenetriamine pentaacetic acid (99mTc-DTPA), from tracheal lumen to
      venous blood in anesthetized sheep. Hyperosmolar liquids increase blood flow and
      slightly decrease 99mTc-DTPA flux, whereas hyposmolar liquids have no effect on
      blood flow and greatly increase 99mTc-DTPA flux. We have now investigated whether
      epithelial damage induced by exposure of the tracheal lumen to a detergent (0.2%
      Triton X-100) alters these effects. A tracheal artery was perfused, and tracheal
      venous blood was collected. The initial tracheal volume was 12.8 +/- 0.7 ml.
      Triton X-100 greatly increased the permeability coefficient for 99mTc-DTPA from 
      2.1 x 10(-7) to -240 x 10(-7) cm/s. Hyperosmolar Krebs-Henseleit solution (KH;
      739 +/- 6 mosmol/kg) increased arterial (+14.3%) and venous (+21.5%) flows and
      decreased 99mTc-DTPA output by 51.7%. Water flux into the lumen (+0.3 +/- 0.1 ml)
      was not significant, and the osmolality decreased by 99 +/- 9 mosmol/kg.
      Hyposmolar KH (124 +/- 2 mosmol/kg) had no effect on arterial and venous flows (
      1.3% for both), and the increase in 99mTc-DTPA output (+8.3%) was small and not
      significant. The volume decreased by 0.4 +/- 0.1 ml, and the osmolaity increased
      by 36 +/- 4 mosmol/kg. Thus epithelial damage greatly increases the baseline
      permeability of the tracheal wall to 99mTc-DTPA. It does not alter the
      qualitative effects of hypersomolar KH on blood flow and 99mTc-DTPA output but
      does reduce the effect of hyposmolar KH on 99mTc-DTPA output. The latter effect
      may be a consequence of the reduced net water movement in response to non
      isosmolar solutions after epithelial damage.

PMID- 7649932
TI  - Physiological determinants of 10-km performance in highly trained female runners
      of different ages.
AB  - Endurance exercise performance declines with age; however, there is little
      information on the mechanisms responsible, especially in women. We tested the
      hypothesis that this performance decline in women is associated with decreases in
      maximal O2 consumption (VO2max), blood lactate threshold (LT), and running
      economy (RE). We determined a 10-km race pace, VO2max, LT, and RE in 31 highly
      trained female runners aged 23-56 yr with similar relative (i.e., age-adjusted)
      competitive performances. Absolute 10-km race pace declined with age (r = -0.83).
      Both 10-km performance and age were correlated with VO2max (P < 0.05) and with
      the running velocity and O2 consumption at LT but not with RE. The runners then
      were divided into three age groups: group I (23-35 yr), group II (37-47 yr), and
      group III (49-56 yr). Stepwise regression analyses performed on subjects pooled
      from groups I and II and from groups II and III indicated that the majority (60%)
      of the variability in performance for runners aged 23-47 yr was explained by the
      running velocity at which LT occurred, whereas VO2max explained the majority
      (74%) of the variability for the runners aged 37-56 yr. We conclude that
      decreases in VO2max and running velocity at LT are the two physiological
      phenomena most closely associated with declines in 10-km performance with age in
      highly trained female runners. However, the contributions of these two mechanisms
      to the declines in performance are not uniform with advancing age.

PMID- 7649934
TI  - Dilatory effects of upper airway muscle contraction induced by electrical
      stimulation in awake humans.
AB  - During sleep, diminished activity of upper airway dilator muscles (UADMs) is
      believed to increase upper airway (UAW) resistance and ultimately cause collapse
      of the UAW. In anesthetized dogs, electrically induced UADM contraction reduces
      UAW resistance and collapsibility. In this study, we measured the effects of
      electrically induced contraction of UADMs on pharyngeal resistance (Rph) in seven
      awake healthy subjects. UAW partial occlusion was achieved by applying external
      pressure to the submental hyoid region, leading to increased Rph. Transmucosal
      electrical stimulation (ES) of the base of the tongue was used to preferentially
      stimulate the genioglossus muscle. Transcutaneous ES using submental and
      paralaryngeal electrodes were used to preferentially stimulate the geniohyoid and
      the sternohyoid and sternothyroid muscles, respectively. During the unobstructed
      state, Rph averaged 6.11 +/- 0.48 cmH2O.l-1.s, and ES produced minimal resistance
      changes for all stimulation sites tested. In contrast, during the application of
      external pressure, when Rph was raised to an average of 190 +/- 14% of the
      baseline value, sublingual ES reduced resistance from 11.67 +/- 1.90 to 6.77 +/-
      1.30 cmH2O.l-1.s (P < 0.01). ES at the other sites during the raised Rph state
      produced only minor statistically insignificant changes in Rph, even when
      combined submental and paralaryngeal ES was applied. Likewise, only sublingual ES
      produced measurable anterior movement of the tongue. We conclude that when Rph is
      raised by exogenous means, sublingual transmucosal ES effectively reduces Rph in
      awake humans.

PMID- 7649933
TI  - Mechanisms of airway protection after pharyngeal fluid infusion in healthy
      sleeping piglets.
AB  - The airway protective mechanisms evoked after infusion of fluids into the pharynx
      were examined in the intact and healthy newborn piglet during sleep. Thirteen
      healthy normothermic piglets (3-6 days of age) were examined on 4 consecutive
      days during sleep. The fluids infused (0.05-1.5 ml) were 0.9% saline, distilled
      water, and HCl (pH 3 and pH 2). Respiratory rate, heart rate, oxygen saturation
      (SaO2), swallowing, and arousal were compared pre- and postinfusion during active
      (AS) and quiet sleep (QS) for each test fluid. The most common response in AS and
      QS was swallowing (90%) and then arousal (24%); however, no apnea occurred, and
      respiratory rate and SaO2 were always maintained. A significant difference
      occurred between HCl infusions of pH 2 and pH 3; at pH 2, the frequency of
      swallows and latency to the first swallow were reduced (P < 0.05) and the
      frequency of arousal was reduced in AS compared with that in QS (P < 0.01).
      Airway protection after pharyngeal fluid stimulation is achieved primarily by
      swallowing and arousal, without any effect on respiratory rate and SaO2.
      Attenuation of protective mechanisms occurred, however, when the infusate was at
      pH 2.

PMID- 7649935
TI  - Longitudinal effects of aging on lung function at rest and exercise in healthy
      active fit elderly adults.
AB  - We retested 18 healthy, active, and highly fit [maximal O2 consumption (VO2max)
      201 +/- 12% of predicted] older adults over a 6-yr period (mean age 67-->73 yr)
      to determine the longitudinal effects of aging on lung function at rest and
      during exercise. In the 6-yr period, total lung capacity (TLC), functional
      residual capacity, and diffusion capacity did not change; vital capacity, forced
      expiratory volume in 1 s, and maximal volitional flow rates decreased; and
      residual volume and closing capacity/TLC increased 11-13%, all of which were
      greater than predicted from cross-sectional data. At maximum exercise over the 6
      yr period, VO2max fell 11.2 +/- 3.4% (45.0-->40.3 ml.kg-1.min-1), six (of 18)
      subjects showed significant arterial hypoxemia (arterial O2 saturation < or =
      92%), and maximum heart rate and minute ventilation-to-O2 consumption ratio
      (VF/VO2) were unchanged. At any given submaximal work rate, VE and breathing
      frequency were higher, the degree of expiratory flow limitation increased, and
      end-expiratory and end-inspiratory lung volumes were unchanged but remained
      significantly higher relative to young adults. We conclude that in contrast to
      implications from cross-sectional data, our longitudinal findings demonstrate
      that habitual physical activity and high aerobic capacity modify neither the
      normal deterioration in resting lung function nor the increased levels of
      ventilatory work during exercise that occur with healthy aging over the sixth and
      seventh decades of life.

PMID- 7649936
TI  - Plasticity of myonuclear number in hypertrophied and atrophied mammalian skeletal
      muscle fibers.
AB  - Although a mammalian skeletal muscle fiber may contain thousands of myonuclei,
      the importance of this number or the potential to modulate it in adult muscle has
      not been clearly demonstrated. Using immunohistochemistry and confocal
      microscopy, we examined the plasticity of myonuclear number and fiber size in
      isolated fast and slow fiber segments from adult cat hindlimb muscles in response
      to chronic alterations in neuromuscular activity and loading. Compared with slow
      fibers in the soleus of control cats, myonuclear number in presumably transformed
      fast fibers was 32% lower and fiber size was decreased 73% after elimination of
      neuromuscular activation for 6 mo by spinal isolation. Slow fibers in the soleus
      of spinal-isolated cats had smaller cross-sectional areas, whereas myonuclear
      number was not significantly different than that in the control cats. Myonuclear
      number in fast plantaris fibers was more than threefold higher and fiber size was
      2.8-fold higher after 3 mo of functional overload compared with the plantaris of
      control cats. Compared with control slow plantaris fibers, myonuclear number and
      fiber size also increased in overloaded slow plantaris fibers. These results
      demonstrate that changes in myonuclear number are associated with changes in
      myosin type and suggest that modulations in the amount of available DNA may be a
      factor in regulating cytoplasmic volume of muscle fibers in response to chronic
      changes in neuromuscular activity.

PMID- 7649937
TI  - Pressure-volume relationships in equine midcarpal joint.
AB  - The effects of joint angle, fluid infusion, history-dependence, and time
      dependence on the pressure-volume (PV) relationships of normal equine midcarpal
      joints were determined. Horses (n = 24 and 48 midcarpal joints) were anesthetized
      and placed in dorsal recumbency, and the four midcarpal joint pouches were
      cannulated for intra-articular pressure (IAP) measurements and recording. Fluid
      (synovial fluid or saline) was infused or withdrawn through the dorsal joint
      capsule. The PV curves were sigmoid and best described by IAP = A x e(B x volume)
      - C, where B is the fractional change in pressure per unit change of volume, and
      A and C are constants. Compartmentation was not observed. Elastance was greater
      at sub- than supra-atmospheric pressures, at 90 degrees than 135 degrees angles,
      and with saline than synovial fluid. Hysteresis was greater at 90 degrees than
      135 degrees angle, and with synovial fluid than saline. Elastance progressively
      increased with sequential distention at high IAPs. IAP relaxation was a positive
      logarithmic relationship of IAP. These findings suggest an important role of
      synovial fluid in articular PV relationships and emphasize the role of joint
      angle, prior distention cycles, and decay of IAP with time in future studies
      investigating these phenomena.

PMID- 7649939
TI  - Effect of lung volume on forced expiratory flows during rapid thoracoabdominal
      compression in infants.
AB  - The rapid thoracoabdominal compression (RTC) technique is commonly used in
      pulmonary function laboratories to assess flow-volume relationships in infants
      unable to produce a voluntary forced expiration maneuver. This technique produces
      forced expiratory flows over only a small lung volume segment (i.e., tidal
      volume). It has been argued that the RTC technique should be modified to measure
      flow-volume relationships over a larger portion of the vital capacity range to
      imitate the voluntary maximal forced expiratory maneuver obtained in older
      children and adults. We examined the effect of volume history on forced
      expiratory flows by generating forced expiratory flow-volume curves by RTC from
      well-defined inspiratory volumes delineated by inspiratory pressures of 10, 20,
      30, and 40 cmH2O down to residual volume (i.e., the reference volume) in seven
      intubated and anesthetized infants with normal lungs [age 8.0 +/- 2.0 (SE) mo,
      weight 6.7 +/- 0.6 kg]. We compared maximal expiratory flows at isovolume points
      (25 and 10% of forced vital capacity) and found no significant differences in
      maximal isovolume flow rates measured from the different lung volumes. We
      conclude that there is no obvious need to initiate RTC from higher lung volumes
      if the technique is used for flow comparisons. However, compared with
      measurements of maximal flows at functional residual capacity by RTC from end
      tidal inspiration, the initiation of RTC from a defined and reproducible
      inspiratory level appears to decrease the intrasubject variability of the maximal
      expiratory flows at low lung volumes.

PMID- 7649938
TI  - Activity of costal and crural diaphragm during progressive hypoxia or
      hypercapnia.
AB  - Because costal and crural diaphragm segments have different functional
      characteristics, ventilatory stimulation with hypoxia or hypercapnia may elicit
      differential segmental function. We report measurements of diaphragm segmental
      length, shortening, and electromyogram (EMG) activity from 11 canines that were
      chronically implanted with sonomicrometry transducers and EMG electrodes and then
      studied a mean of 18 days postimplantation while awake and breathing
      spontaneously during CO2 rebreathing and progressive isocapnic hypoxia.
      Ventilatory responses to hypercapnia and progressive hypoxia were moderate at
      1.13 +/- 0.31 (SD) 1. min-1. mm-1 arterial Pco2 and -0.98 +/- 0.51 l. min
      1.%arterial O2 saturation-1. When tidal values for breathing pattern and
      segmental function were compared at matching tidal volumes that correspond to
      mean CO2 of 49.4 arterial Pco2 and 77% arterial O2 saturation, there was no
      significant difference in resting length, tidal shortening, or tidal EMG of
      costal or crural segments. Intrabreath profiles of flow, shortening, and EMG
      activity at matched tidal volumes showed that 1) inspiratory flow during hypoxia
      was significantly greater during early inspiration, 2) crural EMG activity
      preceded costal EMG activity in early inspiration during both hypercapnia and
      hypoxia, 3) both segments showed increased postinspiratory inspiratory activity
      with stimulated ventilation, and 4) postinspiratory shortening and EMG were
      greatest for the crural segment during hypoxia. These results suggest that costal
      and crural diaphragm segments exhibit differential function during chemical
      stimulation, especially during postinspiration.

PMID- 7649940
TI  - Molecular genetics and cytogenetics of sarcomas.
AB  - It was only 25 years ago that the concept of cancer as a genetic disease began to
      gain widespread acceptance. It is encouraging to note that recurrent molecular
      pathways critical to the genesis and evolution of human sarcomas are being
      elucidated through molecular and cytogenetic techniques. It is also important to
      remember that molecular genetics and cytogenetics are still in their infancy. In
      this review, we have barely touched on the tremendous amount of information that
      has developed in sarcoma genetics and cytogenetics. As this synergistic evolution
      of genetic changes in human sarcomas becomes better understood, new and better
      therapeutic strategies aimed at circumventing these processes will be developed.
      But the biologic and genetic redundancies intrinsic to mammalian cells continue
      to allow tumors to adapt and resist chemotherapeutic agents. Understanding
      sarcoma progression at the molecular level will allow, therefore, for the
      identification of better diagnostic markers, the development of new therapeutic
      strategies, and the ability to select the most effective and least toxic
      combination of antitumor therapies for a patient.

PMID- 7649941
TI  - The importance of the open surgical biopsy in the diagnosis and treatment of bone
      and soft-tissue tumors.
AB  - To obtain the maximal diagnostic benefit from a pretreatment biopsy, an adequate
      amount of tissue should be removed. An open surgical biopsy eminently qualifies
      for such a diagnostic technique because a careful histologic examination of the
      bone or soft-tissue tumor is of particular importance for proper treatment. An
      open biopsy yields the exact diagnosis in most instances.

PMID- 7649942
TI  - Classification and grading of bone sarcomas.
AB  - Bone tumors generally are classified according to the cytologic features or
      products of the lesional cells. In most instances, the classification corresponds
      to a normal cell or tissue type indigenous to bone. This article focuses on
      sarcomas of bone and features a classification scheme similar to what has been
      described at the Mayo Clinic.

PMID- 7649943
TI  - The role of plain radiography, computed tomography, and magnetic resonance
      imaging in sarcoma evaluation.
AB  - Imaging plays an important role in the diagnosis, staging, treatment planning,
      and post-treatment monitoring of bone and soft-tissue sarcomas. Plain radiography
      should be the initial imaging undertaken for patients who present with pain or a
      mass that may represent a musculoskeletal tumor. This is especially true of bony
      lesions, in which plain radiography remains the most specific noninvasive means
      of determining the aggressiveness of a lesion and establishing a working
      differential diagnosis.

PMID- 7649944
TI  - The role of radionuclide scans in sarcoma.
AB  - Images were interpreted and correlated with contemporaneous CT and/or MR imaging
      studies. Visual qualitative analysis of all images was performed by two or more
      nuclear medicine physicians expert in reading these studies. Tracer uptake was
      graded by visual inspection according to the following scale: negative, 0; faint,
      1; moderate, 2; marked, 3. The results indicated that there was a statistically
      significant difference (student T test) in the visual analysis scale obtained
      with MIBI and FDG, indicating better detection (higher sensitivity) of the
      sarcoma with FDG (Table 3). However, the number of cases so far studied is small.
      It is imperative for us to deal with cost effectiveness of our imaging procedures
      in an environment driven by cost containment and managed care initiatives. The
      question posed by the analysis of our work is this: Is the significant difference
      in cost between PET and SPECT justified as far as patient outcome or management
      is concerned? PET scans cost about $2,500 each. A SPECT scan is about $600. Will
      the patient benefit $1900 from the PET intervention? This is an important
      question for which very little objective data are available for evaluation by
      third-party payers, patients, or health care providers.

PMID- 7649945
TI  - Angiography of osteosarcoma.
AB  - During the last two decades, the excellent sectional imaging provided by computed
      tomography and magnetic resonance has determined that conventional angiography no
      longer be routinely performed in the diagnosis of sarcomas. Conventional
      angiography, however, is a helpful adjunct to the biopsy of parosteal
      osteosarcoma when chemotherapy is administered intraarterially.

PMID- 7649946
TI  - Core needle biopsy and fine-needle aspiration in the diagnosis of bone and soft
      tissue lesions.
AB  - Although core needle biopsy (CNB) and fine needle aspiration (FNA) procedures are
      widely used for the diagnosis of epithelial neoplasms, these procedures have not
      gained popularity on patients suspected of having bone or soft-tissue neoplasms.
      This article describes the University of Texas, M.D. Anderson Cancer Center
      experience with CNB and FNA procedures in bone and soft tissue performed in over
      800 patients.

PMID- 7649947
TI  - Classification and grading of soft-tissue sarcomas. A comment.
AB  - A contrary viewpoint concerning certain issues in soft-tissue sarcoma pathology
      is presented. Three issues emphasized are (1) the role of immunocytochemistry and
      electron microscopy in diagnosis, (2) the classification of liposarcomas and
      atypical lipomatous tumors, and (3) the validity and usefulness of histologic
      grading.

PMID- 7649948
TI  - Immunohistochemistry and DNA flow cytometry in soft-tissue sarcomas.
AB  - Immunohistochemistry has a major role as an adjunct to light microscopy in the
      diagnosis and classification of soft tissue sarcomas. Immunohistochemical
      analysis of proliferation markers appears so far to add very little to accurate
      and experienced histologic typing of soft-tissue sarcomas. Immunohistochemical
      assessment of tumor suppressor genes and oncogene products gives an insight into
      pathogenetic mechanisms but does not appear to correlate reliably with clinical
      outcome. Analysis of ploidy by DNA flow cytometry does not separate benign from
      malignant lesions, and assessment of cell proliferation by this method does not
      seem to predict clinical behavior accurately.

PMID- 7649949
TI  - Classification and grading of soft-tissue sarcomas.
AB  - This article provides an overview of the classification of soft-tissue sarcomas
      as influenced by modern histopathologic techniques. The overview is followed by a
      practical grading system for these tumors based on a study of 282 eligible
      patients. The primary tumors of this trial were adequately treated. The
      quantitative data (mitotic count and size of the tumor) were based on the results
      of the statistical analysis.

PMID- 7649950
TI  - Subgroups of adolescent depression.

PMID- 7649951
TI  - White matter hyperintensities.

PMID- 7649952
TI  - Generic bioequivalence.

PMID- 7649953
TI  - Practical guidelines for the assessment and treatment of selective mutism.
AB  - OBJECTIVE: To provide practical guidelines for the assessment and treatment of
      children with selective mutism, in light of the recent hypothesis that selective
      mutism might be best conceptualized as a childhood anxiety disorder. METHOD: An
      extensive literature review was completed on the phenomenology, evaluation, and
      treatment of children with selective mutism. Additional recommendations were
      based on clinical experience from the authors' selective mutism clinic. RESULTS:
      No systematic studies of the phenomenology of children with selective mutism were
      found. Reports described diverse and primarily noncontrolled treatment approaches
      with minimal follow-up information. Assessment and treatment options for
      selective mutism are presented, based on new hypotheses that focus on the anxiety
      component of this disorder. Ongoing research suggests a role for behavior
      modification and pharmacotherapy similar to the approaches used for adults with
      social phobia. CONCLUSION: Selectively mute children deserve a comprehensive
      evaluation to identify primary and comorbid problems that might require
      treatment. A school-based multidisciplinary individualized treatment plan is
      recommended, involving the combined effort of teachers, clinicians, and parents
      with home- and clinic-based interventions (individual and family psychotherapy,
      pharmacotherapy) as required.

PMID- 7649954
TI  - Psychiatric characteristics of children with selective mutism: a pilot study.
AB  - OBJECTIVE: To ascertain characteristics of children with selective mutism.
      METHOD: Subjects with selective mutism were evaluated by means of parent and
      teacher rating scales and structured diagnostic interviews. RESULTS: Thirty
      children were evaluated. Mutism severity varied markedly in different
      environmental settings. Ninety-seven percent of the subjects were diagnosed with
      social phobia or avoidant disorder of childhood or adolescence or both and 30%
      with simple phobia. No other psychiatric disorders were common. Parent and
      teacher rating scales showed high levels of anxiety symptoms, especially social
      anxiety, and low levels of all other psychiatric symptoms. Anxiety and social
      anxiety severity correlated with mutism severity. First-degree family history of
      social phobia and of selective mutism, obtained by family history method, was
      present in 70% and 37% of families, respectively. There was no evidence of a
      causal relationship between psychologically or physically traumatic experiences
      and development of selective mutism. CONCLUSIONS: Selective mutism may be a
      symptom of social anxiety, rather than a distinct diagnostic syndrome. Further
      study of the characteristics of children with selective mutism and their families
      is warranted.

PMID- 7649955
TI  - Case study: fluoxetine in the multimodal treatment of a preschool child with
      selective mutism.
AB  - Selective mutism is a rare disorder with poor treatment outcome. The current
      study describes the successful treatment of selective mutism in a preschool-age
      girl, using a comprehensive multifaceted therapeutic approach. The components of
      this intervention reflect a conceptualization of selective mutism that emphasizes
      anxiety as a core feature but also focuses on associated factors such as
      oppositional behaviors.

PMID- 7649956
TI  - Case study: is selective mutism a manifestation of dissociative identity
      disorder?
AB  - Selective mutism is a rare psychiatric disorder that usually has its onset in
      early childhood. This case study describes a patient in whom selective mutism
      developed in adolescence. It was later discovered that he had dissociative
      identity disorder. The study documents his history, which included violence,
      abuse, and threats to keep silent. The study suggests that in cases presenting
      with significant trauma or abuse, selective mutism may be a manifestation of
      dissociative identity disorder.

PMID- 7649957
TI  - Mania-like symptoms suggestive of childhood-onset bipolar disorder in clinically
      referred children.
AB  - OBJECTIVE: To examine the prevalence, characteristics, and correlates of mania
      among referred children aged 12 or younger. Many case reports challenge the
      widely accepted belief that childhood-onset mania is rare. Sources of diagnostic
      confusion include the variable developmental expression of mania and its
      symptomatic overlap with attention-deficit hyperactivity disorder (ADHD). METHOD:
      The authors compared 43 children aged 12 years or younger who satisfied criteria
      for mania, 164 ADHD children without mania, and 84 non-ADHD control children.
      RESULTS: The clinical picture was fully compatible with the DSM-III-R diagnosis
      of mania in 16% (n = 43) of referred children. All but one of the children
      meeting criteria for mania also met criteria for ADHD. Compared with ADHD
      children without mania, manic children had significantly higher rates of major
      depression, psychosis, multiple anxiety disorders, conduct disorder, and
      oppositional defiant disorder as well as evidence of significantly more impaired
      psychosocial functioning. In addition, 21% (n = 9) of manic children had had at
      least one previous psychiatric hospitalization. CONCLUSIONS: Mania may be
      relatively common among psychiatrically referred children. The clinical picture
      of childhood-onset mania is very severe and frequently comorbid with ADHD and
      other psychiatric disorders. Because of the high comorbidity with ADHD, more work
      is needed to clarify whether these children have ADHD, bipolar disorder, or both.

PMID- 7649958
TI  - Do high doses of stimulants impair flexible thinking in attention-deficit
      hyperactivity disorder?
AB  - OBJECTIVE: To test the hypothesis that high doses of methylphenidate (MPH) impair
      cognitive flexibility in attention-deficit hyperactivity disorder (ADHD). METHOD:
      A double-blind crossover design was used in an acute dosage trial to assess
      effects of three dosages (0.3, 0.6, and 0.9 mg/kg) of MPH on the performance of
      17 ADHD children on five tasks designed to assess divergent thinking,
      perseveration, and ability to shift mental set. The tasks also assessed
      convergent thinking, problem solving, and speed and accuracy of processing.
      RESULTS: There was minimal evidence of deleterious effects on flexible thinking
      or other cognitive processes, either in the ADHD group as a whole or in any
      subgroup. The most common pattern indicated linear improvement across dosages.
      CONCLUSIONS: Under the acute dosage conditions used in this study, MPH doses up
      to 0.9 mg/kg had an increasingly positive effect on measures of mental
      flexibility and other cognitive processes. Rather than eliciting perseveration,
      MPH appeared to improve persistence. The generalized nature of the cognitive and
      motivational changes observed suggests that MPH acts on central, self-regulatory
      processes. Because effects of two or more daily doses can accumulate when MPH is
      prescribed in the clinical situation, clinical doses of more than 0.6 mg/kg were
      not recommended.

PMID- 7649959
TI  - Differential effects of methylphenidate on working memory in ADHD children with
      and without comorbid anxiety.
AB  - OBJECTIVE: To examine the effects of methylphenidate (MPH) on working memory and
      behavior in anxious and nonanxious children with attention-deficit hyperactivity
      disorder (ADHD). METHOD: A total of 40 ADHD children (22 nonanxious, 18 anxious)
      completed a randomized, double-blind, placebo-controlled, crossover trial with
      three doses (0.3, 0.6, 0.9 mg/kg) of MPH. A serial addition task was used to
      assess working memory; direct observation of motor activity indexed behavior.
      RESULTS: MPH improved working memory in the nonanxious ADHD group but not in the
      comorbidity anxious group. By contrast, MPH reduced activity level in both
      groups. The presence of concurrent learning disabilities did not influence
      stimulant response. CONCLUSIONS: The presence of comorbid anxiety in children
      with ADHD predicts a less robust response to stimulant treatment and suggests
      that ADHD with anxiety may constitute a distinct and clinically meaningful
      subtype of ADHD.

PMID- 7649960
TI  - Effects of methylphenidate on reward strength in boys with attention-deficit
      hyperactivity disorder.
AB  - OBJECTIVE: To test the hypothesis that methylphenidate reduces thresholds for
      reward in children with attention-deficit hyperactivity disorder (ADHD). METHOD:
      A double-blind crossover design was used in which 16 ADHD boys, aged 8 to 13
      years, received methylphenidate on one testing occasion and placebo on another.
      On each occasion, subjects performed a task that required progressively greater
      numbers of button presses to earn a fixed monetary payoff. RESULTS: The "breaking
      point" above which the hyperactive child was unwilling to continue with the task
      was significantly higher during drug than placebo trials. CONCLUSIONS: The
      results support an assumption that underlies the reward system dysfunction
      hypothesis of ADHD, and they suggest that reward mechanisms may underlie the
      therapeutic effects of stimulants observed across a wide range of tasks and
      settings.

PMID- 7649961
TI  - Hospitalizing the suicidal adolescent: an empirical investigation of decision
      making criteria.
AB  - OBJECTIVE: The primary purpose of this research is to investigate the criteria
      used by child and adolescent clinicians in determining the appropriateness of
      hospitalization for suicidal adolescents. METHOD: A questionnaire containing 64
      vignettes describing adolescent suicide attempters was completed by a sample of
      36 child and adolescent clinicians. Six variables known to relate to lethality of
      attempt were systematically varied within the vignettes: gender, depression,
      conduct disorder/substance abuse, previous attempts, suicidal relative, and
      family supports. Respondents were asked to judge the appropriateness of
      hospitalization for each vignette. RESULTS: Hospitalization preference was found
      to be inversely related to professional experience and was significantly
      predicted by all risk factors except gender. Configural cue utilization added
      substantially to the efficacy of a linear model in predicting preference to
      hospitalize. CONCLUSIONS: Experienced clinicians use known risk factors for
      adolescent suicide in making recommendations to hospitalize, but results also
      suggest ongoing needs for education and training in adolescent suicidality.

PMID- 7649962
TI  - Correlation of suicidal and violent behavior in different diagnostic categories
      in hospitalized adolescent patients.
AB  - OBJECTIVE: To determine the relative importance of aggression and depression in
      adolescent suicide within different diagnostic categories. METHOD: One hundred
      sixty-three consecutive admissions to an adolescent psychiatric inpatient unit
      were assessed using a semistructure diagnostic instrument, the Schedule for
      Affective Disorders and Schizophrenia for School-Age Children. Scores for
      depression, suicidal behaviors, and violent behaviors were calculated from this
      assessment. RESULTS: Anorexia nervosa and conduct disorder patients had the
      highest suicidal behavior scores. In addition, patients with conduct disorder
      were significantly more violent than patients with major depressive disorder, and
      scores on the Violent Behavior Scale correlated with suicidal symptoms but not
      with depressive symptoms. CONCLUSION: Aggression may be as important in some
      kinds of suicidal behaviors as is depression. Thus it seems that there are
      hypothetically at least two types of suicidal behaviors during adolescence: a
      wish to die (depression) and a wish not to be here for a time (impulse control).
      The first type of suicidal behavior characterizes that seen in disorders with
      prominent depression such as major depressive disorder and anorexia nervosa, and
      the second characterizes disorders of impulse control such as conduct disorder.

PMID- 7649963
TI  - Self-esteem deficits and suicidal tendencies among adolescents.
AB  - OBJECTIVE: Self-esteem can play an important role in suicidal tendencies among
      adolescents. The present study was designed to examine the relationship between
      self-esteem deficits and suicidal tendencies in 254 adolescent psychiatric
      inpatients and 288 high school students. METHOD: The direct relationship between
      self-esteem and suicidal tendencies was examined by assessing suicidal ideation
      and history of suicide attempts. An indirect relationship between self-esteem and
      suicidality was examined by assessing depression and hopelessness. RESULTS:
      Differences were found across gender and hospitalization status, with males
      reporting higher self-esteem than females and high school students scoring higher
      in self-esteem than psychiatric inpatients. However, correlations among variables
      remained similar across gender and hospitalization status. Thus, low self-esteem
      was related to higher levels of depression, hopelessness, suicidal ideation, and
      an increased likelihood of having previously attempted suicide. Furthermore, self
      esteem added to the understanding of suicidal ideation beyond what could be
      explained by depression and hopelessness. CONCLUSIONS: Low self-esteem was
      closely related to feelings of depression, hopelessness, and suicidal tendencies.
      Assessment of adolescents should include an evaluation of self-esteem, and
      therapy should attempt to address any self-esteem deficits.

PMID- 7649964
TI  - Ethical issues in biological psychiatric research with children and adolescents.
AB  - OBJECTIVE: This article reviews, discusses, and elaborates considerations and
      recommendations summarized by the biological research working group at the May
      1993 NIMH conference on ethical issues in mental health research on children and
      adolescents. METHOD: Notes from the conference were summarized and supplemented
      by a computer search of relevant literature. Drafts were circulated for comment
      to national and international experts, some of whom joined as coauthors. RESULTS:
      Issues addressed include possible overprotection by policy makers and
      institutional review boards arising out of the recognition of children's special
      vulnerability without equal recognition of their need for research; the
      definition of minimal risk, which has often been equated with no risk in the case
      of children; assessment of the risk-benefit ratio; procedures for minimization of
      risk, such as improved technology, "piggybacking" onto clinical tests, and age
      appropriate preparation; the difficulty of justifying risk for normal controls;
      age-graded consent; special considerations about neuroimaging; "coercive"
      inducement, both material and psychological; disposition of unexpected or
      unwanted knowledge about individuals, including the subject's right not to know
      and parent's right not to tell; and socioeconomic status and cultural/ethnic
      equity. CONCLUSIONS: The working group adopted a position of advocacy for
      children's right to research access while recognizing that this advocacy must be
      tempered by thoughtful protections for child and adolescent subjects.

PMID- 7649965
TI  - Consumer satisfaction with involvement in drug research: a social validity study.
AB  - OBJECTIVE: To assess the social importance and personal benefit attached to
      involvement in drug research for participating families. METHOD: Parents of
      children with mental retardation or borderline IQ who took part in two drug
      studies were surveyed by mail 4 weeks after their involvement. The questionnaire
      addressed the acceptability of study procedures and satisfaction with study
      outcomes ("social validity"). RESULTS: Forty (63.5%) of 63 families responded to
      the survey. In all, 83% felt that their questions were satisfactorily answered
      regarding the role of medication for their children, and 88% were satisfied with
      the individual conclusions reached regarding pharmacotherapy for their children.
      Virtually all parents believed that the study assessments used were important,
      and 88% indicated that they would join the study again if faced with the same
      choices. CONCLUSIONS: These parents appear to have found the research experience
      to be of practical benefit to them, and they were generally positive about their
      experiences. As this seems to be the only published study of the social or
      perceived validity of drug research, more surveys of this type are needed to
      assess consumer reactions to a broader array of research experiences.

PMID- 7649966
TI  - Do children aged 9 through 11 years understand the DISC Version 2.25 questions?
AB  - OBJECTIVE: To assess the understanding of Diagnostic Interview Schedule for
      Children-Version 2.25 (DISC-2.25) questions by children aged 9 through 11 years.
      METHOD: Two hundred forty children were recruited from four public schools. The
      cognitive appraisal of 280 questions from the most prevalent DSM-III-R diagnoses
      was evaluated. The collaboration of four children was necessary to cover one
      DISC. Sixty DISCs, evenly distributed according to age and sex, were completed.
      Two child psychiatrists evaluated the children's answers. Nonparametric tests
      were used to assess understanding of questions as a whole, of time concepts
      (overall, categories, number), and of questions based on the number of words.
      RESULTS: Children aged 9, 10, and 11 years understood 38%, 38%, and 42% of the
      questions as a whole, respectively, and 26%, 24%, and 30% of the overall time
      concepts, respectively. The understanding rates of questions as a whole were
      significantly higher than those of overall time concepts. Durations were
      significantly better understood than periods and frequencies, and questions
      having one time component were significantly better grasped than those with two
      or more. Shorter questions were significantly better understood than longer ones.
      CONCLUSION: Although the DISC has been greatly improved since the initial
      version, the results suggest that additional revision is needed before clinicians
      or researchers use the DISC with younger children.

PMID- 7649967
TI  - Resolved: multiple personality disorder is an individually and socially created
      artifact.

PMID- 7649969
TI  - Anxiety symptom relief in depression treatment outcomes.
AB  - Depressive and anxiety disorders have a high lifetime prevalence--8% and 15%,
      respectively. Unipolar depression has a 5% lifetime prevalence, whereas the
      prevalence rate for all depressive disorders is between 6% to 8% at a minimum.
      Each disorder has also been found to have a high rate of chronicity and
      recurrence. It has become increasingly apparent over the past decade that within
      episodes of depression, anxiety symptoms often exist. Whether this phenomenon
      indicates two separate but comorbid illnesses or that the presence of anxiety
      symptoms is part of the course of depression is of particular significance for
      diagnosis and treatment. The author focuses on the issues of differential
      diagnosis, including physical and emotional manifestations of the illness. The
      consequences of comorbid anxiety and depression can be serious, ranging from
      social and physical disability to suicidal ideation and behavior. Anxiety has
      been found to be a predictor of suicide in depressed patients, and since anxiety
      symptoms respond to intervention, they can also serve as an indication of type of
      treatment. Antidepressants should be used in treating anxiety or panic symptoms
      when depression is also present. In studies comparing benzodiazepines, monoamine
      oxidase inhibitors (MAOIs), serotonin selective reuptake inhibitors (SSRIs), and
      tricyclic antidepressants (TCAs) in the treatment of concurrent anxiety and
      depression, all have some measure of success depending on the degree of
      depression and the type of anxiety disorder. SSRIs may have the least amount of
      side effects, but more long-term studies are needed to determine the long-term
      efficacy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7649968
TI  - Comparison of the tolerability of bupropion, fluoxetine, imipramine, nefazodone,
      paroxetine, sertraline, and venlafaxine.
AB  - Drug development in psychiatry has evolved from a process dependent on chance
      discovery to one based on rationally targeting specific mechanisms of action
      believed to be important in the pathophysiology underlying psychiatric syndromes.
      Antidepressant pharmacotherapy is the first area to have substantially benefited
      from this evolution. Serotonin selective reuptake inhibitors (SSRIs) were the
      first class of psychiatric medications developed based on such molecular
      targeting. Nefazodone is a new antidepressant that combines blockade of the
      serotonin-2 receptor with serotonin uptake inhibition. Perhaps as a result of
      this dual action, nefazodone caused fewer complaints of nervousness (e.g.,
      agitation, anxiety), insomnia, and tremors and a higher incidence of confusion,
      dizziness, and vision disturbance than do other advanced generation
      antidepressants based on several different ways of assessing the relative
      incidence of these adverse effects. Reports of sexual dysfunction on nefazodone
      and bupropion treatment were lower than on treatment with other recently released
      antidepressants.

PMID- 7649970
TI  - Pharmacology and neurochemistry of nefazodone, a novel antidepressant drug.
AB  - Nefazodone is a new antidepressant drug with a pharmacologic profile distinct
      from that of the tricyclic, monoamine oxidase inhibitor, and serotonin selective
      reuptake inhibitor antidepressants. Nefazodone was initially discovered for its
      ability to block 5-HT2A receptors and its reduced potency as an alpha 1
      adrenergic blocker. It was later shown to inhibit both serotonin and
      norepinephrine uptake in vitro, attributes which most likely impart its clinical
      efficacy and which differentiate nefazodone from its chemical predecessor
      trazodone. The combination of these two mechanisms may ultimately result in a
      facilitation of 5-HT1A-mediated neurotransmission, which may be beneficial for
      treating symptoms of depression as evidenced by recent clinical findings. In
      addition, the preclinical profile of nefazodone demonstrates that it has
      decreased anticholinergic and antihistaminic activity relative to traditional
      agents. Clinical findings to date are consistent with these observations.

PMID- 7649971
TI  - A double-blind, placebo-controlled trial of two dose ranges of nefazodone in the
      treatment of depressed outpatients.
AB  - BACKGROUND: Nefazodone hydrochloride, a 5-HT2 receptor antagonist that
      selectively inhibits serotonin reuptake, was evaluated in a double-blind, dose
      finding study of novel design, involving 240 patients with major depression.
      METHOD: Patients were randomly assigned to three treatment groups and received
      either placebo (2-6 capsules per day), a lower-dose range of nefazodone (50-300
      mg/day), or a higher-dose range of nefazodone (100-600 mg/day) for 6 weeks.
      RESULTS: At the end of treatment, the Hamilton Rating Scale for Depression and
      the clinician- and patient-rated Inventory for Depressive Symptomatology scores
      showed significant improvement (p < or = .05) for patients receiving higher-dose
      range nefazodone (mean = 392 mg/day) compared with placebo treatment. The
      percentage of responders (at least "much improved" on the Clinical Global
      Impressions-Improvement scale) in the higher-dose range nefazodone group (58%)
      was significantly greater (p < or = .05) than in the placebo group (39%). The
      treatment group receiving nefazodone in the lower-dose range was not
      differentiated in clinical response from placebo controls. The rate of
      discontinuation for adverse experience (14%) was similar for patients treated
      with higher-dose range nefazodone and placebo. CONCLUSION: The findings of this
      study indicate that nefazodone is an effective and well-tolerated antidepressant
      drug, with a recommended therapeutic dose range of 100 to 600 mg/day and a
      starting dose of 100 mg b.i.d.

PMID- 7649974
TI  - Structural determinants of neurotrophin action.
AB  - Five decades of research on NGF have led to the discovery of a small family of
      evolutionarily conserved proteins, which have vital functions in the survival and
      neuronal development of specific neuronal populations. The generation of mice
      lacking neurotrophin expression has recapitulated classic experiments using anti
      NGF antibodies to dissect the physiological effects of trophic factor deprivation
      (73). Very similar outcomes resulted from both the NGF immunodepletion
      experiments and the transgenic mouse experiments. The genetic results also verify
      the structural predictions made from binding results in heterologous cells. The
      findings in cell culture and animal experiments clearly indicate the efficacy of
      neurotrophic factors for promoting the survival of prominent neuronal populations
      such as sensory and motor neurons. The high degree of conservation of
      neurotrophin structure is accompanied by a surprising variation in the amino acid
      contacts used by each neurotrophin with p75 and the trk receptor family members.
      It is this variation that may provide specificity for each ligand-receptor
      complex. The future challenge will be to make use of this knowledge to design
      effective therapeutic strategies to treat neurodegeneration and nerve injury.

PMID- 7649973
TI  - Nefazodone: aspects of efficacy.
AB  - BACKGROUND: Nefazodone hydrochloride, a 5-HT2 receptor antagonist and serotonin
      (5-HT) uptake inhibitor, was evaluated in four Phase 3 double-blind, imipramine-
      and placebo-controlled studies involving outpatients with major depression.
      METHOD: Patients who qualified for well-controlled efficacy trials in major
      depression were enrolled in a series of active- and placebo-controlled trials to
      establish the comparative efficacy of nefazodone and a standard tricyclic
      antidepressant drug. The primary efficacy measures employed were the 17-item
      Hamilton Rating Scale for Depression (HAM-D-17) and the Clinical Global
      Improvement (CGI) scale. Safety profiles were also compared as well as survival
      analyses of double-blind acute and continuation treatment of patients in efficacy
      trials. RESULTS: Three of four Phase 3 active- and placebo-controlled studies
      showed nefazodone to be an effective antidepressant drug with overall efficacy
      generally similar to that of imipramine. The remaining study did not
      differentiate either active drug from placebo controls. Superiority of nefazodone
      and imipramine over placebo was evidenced by greater improvement on core
      depression symptoms in addition to the primary outcome measures (HAM-D-17 and
      CGI). The incidence of side effects and premature treatment discontinuations for
      imipramine-treated patients was higher than for nefazodone therapy. Both drugs
      showed evidence of continuing efficacy during long-term treatment with
      significantly fewer dropouts (p < .05) than for placebo controls. CONCLUSION:
      Nefazodone, an antidepressant that modulates serotonin receptors and enhances
      serotonin-mediated neurotransmission, has been shown to be an effective and well
      tolerated new antidepressant drug with greater patient acceptability and safety
      than imipramine.

PMID- 7649972
TI  - Response of anxiety and agitation symptoms during nefazodone treatment of major
      depression.
AB  - A meta-analysis of six randomized, placebo-controlled, double-blind trials was
      carried out to evaluate the effectiveness of the new antidepressant nefazodone in
      relieving symptoms of anxiety and agitation associated with major depression.
      Nefazodone blocks serotonin2 (5-HT2) receptors and selectively inhibits serotonin
      (5-HT) reuptake. This pharmacologic profile may confer clinical benefits that
      differ from those of other antidepressants, such as tricyclics (TCAs) and
      serotonin selective reuptake inhibitors (SSRIs). The data base included 817
      patients with major depression and baseline 17-item Hamilton Rating Scale for
      Depression (HAM-D-17) scores > or = 18; 345 received placebo, 288 imipramine, and
      184 nefazodone. Both nefazodone and imipramine exhibited antidepressant efficacy
      compared with that of placebo, irrespective of baseline anxiety levels.
      Statistically significant improvement in Hamilton Rating Scale for Anxiety (HAM
      A), HAM-D anxiety factor, HAM-D psychic anxiety item, and HAM-D agitation item
      scores was observed with both active treatments. Nefazodone-treated patients
      showed significantly greater improvement in somatic anxiety (HAM-D item 11)
      ratings than placebo-treated patients from Week 4 through end of treatment (p <
      or = .01), while imipramine-treated patients did not differ from placebo patients
      on this item. Nefazodone-treated patients improved more rapidly (as early as Week
      1) than imipramine- and placebo-treated patients on agitation (HAM-D item 9) (p <
      or = .01). Nefazodone was found to have an excellent safety profile and was well
      tolerated, with 5% of nefazodone patients prematurely discontinuing treatment for
      adverse experiences compared with 17% for imipramine and 5% for placebo
      treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7649975
TI  - Thrombopoietin induces megakaryocyte differentiation in hematopoietic progenitor
      FDC-P2 cells.
AB  - Thrombopoietin (Tpo) is a cytokine that specifically regulates megakaryocyte
      maturation and platelet production. Little is known about the molecular and
      cellular mechanism of the Tpo-induced megakaryocyte maturation process including
      polyploidization and platelet release. To study Tpo-induced megakaryocyte
      differentiation, a mouse cell line FD-TPO, which responds and grows with Tpo, was
      established from a interleukin-3-dependent hematopoietic progenitor cell line FDC
      P2. The FD-TPO cells, expressing endogenous Tpo receptor, grew with Tpo in a dose
      dependent manner. Further, Tpo stimulation dramatically induced expression of
      megakaryocyte/erythroid-specific transcription factors GATA-1 and NF-E2 in FD-TPO
      cells. Flow cytometry analysis demonstrated that expression of platelet-specific
      cell surface antigens including CD61 (GPIIIa) dramatically increased in Tpo
      stimulated FD-TPO cells and that expression of myeloid-specific antigens, Gr-1
      and Mac-1, decreased. Therefore, we concluded that the binding of Tpo to FD-TPO
      cells induces not only cell growth but also differentiation into mature
      megakaryocyte-like cells, and thus this cell line was found to be useful for the
      study of Tpo receptor-mediated growth and differentiation signals.

PMID- 7649976
TI  - Differential regulation of JunD by dihydroxycholecalciferol in human chronic
      myelogenous leukemia cells.
AB  - 1,25-Dihydroxyvitamin D3 inhibits the proliferation of the chronic myelogenous
      leukemia cell line RWLeu-4 but not the resistant variant, JMRD3. Although these
      cells exhibit no detectable differences in the vitamin D receptor, alterations in
      the interaction of nuclear extracts with the osteocalcin-1,25-dihydroxyvitamin D3
      response element are noted. It is shown herein that the 1,25-dihydroxyvitamin D3
      receptor binds to the osteocalcin-1,25-dihydroxyvitamin D3-response element along
      with activator protein-1 (AP-1) complexes and that the DNA binding activities of
      members of the Jun and Fos proto-oncogene families, which make up the AP-1
      transcription factor, are differentially regulated by 1,25-dihydroxyvitamin D3.
      It is shown that JunD DNA binding activity is enhanced by 1,25-dihydroxyvitamin
      D3 during cell cycle arrest in the sensitive cells but is decreased in the
      resistant cells. These results suggest that the level of JunD DNA binding
      activity may be a critical factor in the regulation of proliferation.

PMID- 7649977
TI  - p53 and Sp1 interact and cooperate in the tumor necrosis factor-induced
      transcriptional activation of the HIV-1 long terminal repeat.
AB  - Tumor necrosis factor alpha (TNF) is a potent activator of transcription directed
      by the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR). We
      have recently reported that the p53 tumor suppressor gene product binds to a site
      within the Sp1 binding region of the HIV-1 LTR and contributes to the TNF
      induction of this promoter. In this study we show that the transcription factor
      Sp1 cooperates with p53 in the transcriptional activation directed by the HIV-1
      LTR. The presence of Sp1 increased p53 binding to its recognition sequence in the
      HIV-1 LTR, and experiments in Drosophila cells show that Sp1 is necessary for
      full transactivation by mutant p53. Importantly, TNF induced the association
      between p53 and Sp1 in Jurkat T cells. These data demonstrate a synergistic role
      for these proteins in the mechanism of TNF induction of HIV-1 LTR-mediated
      transcription and suggest that Sp1 may play an important role in modulating
      certain functions of p53.

PMID- 7649978
TI  - In vitro motility analysis of smooth muscle caldesmon control of actin
      tropomyosin filament movement.
AB  - We have used the in vitro motility assay to investigate the effect of caldesmon
      on the movement of actin-tropomyosin filaments over thiophosphorylated smooth
      muscle myosin and skeletal muscle heavy meromyosin. Using either motor,
      incorporation of up to 8 nM caldesmon inhibited filament movement by decreasing
      the proportion of filaments motile from > 85% to < 30%. There was a minimal
      effect on filament attachment and a modest decrease in motile filament velocity
      in this concentration range. The reduction in the proportion of filaments motile
      could be completely reversed by incorporation of an excess of calmodulin at pCa
      4.5. The expressed C-terminal fragment, 606C, which retains caldesmon's
      inhibitory capacity but does not bind to myosin, decreased the proportion of
      filaments motile but had no effect on velocity. We conclude that the velocity
      reduction by whole caldesmon is due to actin-myosin cross-linking. A significant
      decrease in filament attachment was observed when caldesmon was added to an
      excess over actin (> 10 nM). In the absence of tropomyosin, addition of an excess
      of caldesmon caused a similar decrease in the filament density, but there was no
      effect on the proportion of filaments that were motile. Our results demonstrate
      that caldesmon can switch actin-tropomyosin from motile to non-motile states
      without controlling velocity of movement or weak binding affinity and show the
      inhibitory action of caldesmon in the motility assay to be functionally
      indistinguishable from that reported for troponin.

PMID- 7649979
TI  - Fasciculin 2 binds to the peripheral site on acetylcholinesterase and inhibits
      substrate hydrolysis by slowing a step involving proton transfer during enzyme
      acylation.
AB  - The acetylcholinesterase active site consists of a gorge 20 A deep that is lined
      with aromatic residues. A serine residue near the base of the gorge defines an
      acylation site where an acyl enzyme intermediate is formed during the hydrolysis
      of ester substrates. Residues near the entrance to the gorge comprise a
      peripheral site where inhibitors like propidium and fasciculin 2, a snake
      neurotoxin, bind and interfere with catalysis. We report here the association and
      dissociation rate constants for fasciculin 2 interaction with the human enzyme in
      the presence of ligands that bind to either the peripheral site or the acylation
      site. These kinetic data confirmed that propidium is strictly competitive with
      fasciculin 2 for binding to the peripheral site. In contrast, edrophonium, N
      methylacridinium, and butyrylthiocholine bound to the acylation site and formed
      ternary complexes with the fasciculin 2-bound enzyme in which their affinities
      were reduced by about an order of magnitude from their affinities in the free
      enzyme. Steady state analysis of the inhibition of substrate hydrolysis by
      fasciculin 2 revealed that the ternary complexes had residual activity. For
      acetylthiocholine and phenyl acetate, saturating amounts of the toxin reduced the
      first-order rate constant kcat to 0.5-2% and the second-order rate constant
      kcat/Kapp to 0.2-2% of their values with the uninhibited enzyme. To address
      whether fasciculin 2 inhibition primarily involved steric blockade of the active
      site or conformational interaction with the acylation site, deuterium oxide
      isotope effects on these kinetic parameters were measured. The isotope effect on
      kcat/Kapp increased for both substrates when fasciculin 2 was bound to the
      enzyme, indicating that fasciculin 2 acts predominantly by altering the
      conformation of the active site in the ternary complex so that steps involving
      proton transfer during enzyme acylation are slowed.

PMID- 7649980
TI  - Amyloid beta-protein inhibits ubiquitin-dependent protein degradation in vitro.
AB  - Intraneuronal accumulation of ubiquitin conjugates in inclusion bodies and
      neurofibrillary tangles is a pathological feature of neurodegenerative disorders
      such as Alzheimer's disease and Down's syndrome and of normal aging of the brain.
      Amyloid beta-protein (A beta) and its precursor are found in neurofibrillary
      tangle-containing neurons. A beta is the major component of extracellular
      plaques. We showed that A beta acts as an inhibitor of the ubiquitin-dependent
      protein degradation in vitro. We examined the effect of A beta on the steps of
      this proteolytic pathway that contribute to the level of ubiquitin conjugates in
      the cell. Neither conjugate formation nor conjugate deubiquitination was affected
      by the presence of A beta. However, A beta significantly reduced the rate of
      conjugate degradation. Our results indicate that A beta interacts with the
      proteolytic step of the ubiquitin degradative pathway. Since this step is
      performed by the 26 S proteasome, the effect of A beta on the catalytic core of
      this proteolytic complex, the 20 S proteasome, was determined. We found that A
      beta selectively inhibits the chymotrypsin-like activity of the 20 S proteasome.
      Under pathological conditions in the affected neuron, A beta could interfere with
      ubiquitin-dependent degradation by inhibiting the 26 S proteasome activity. This
      finding may explain the origin of the accumulation of ubiquitin conjugates.

PMID- 7649981
TI  - Biosynthesis of the side chain of yeast glycosylphosphatidylinositol anchors is
      operated by novel mannosyltransferases located in the endoplasmic reticulum and
      the Golgi apparatus.
AB  - Glycosylphosphatidylinositol (GPI) anchors of the yeast Saccharomyces cerevisiae
      have been reported to contain three different types of side chains attached to
      contain three different types of side chains attached to the alpha 1,2-linked
      mannose of the conserved protein-ethanolamine-PO4-Man alpha 1,2Man alpha 1,6Man
      alpha 1,4GlcNH2-inositol glycan core. The possible side chains are Man alpha 1,2-
      or Man alpha 1,2Man alpha 1,2- or Man alpha 1,3Man alpha 1,2- (Fankhauser, C.,
      Homan, S. W., Thomas Oates, J. E., McConville, M. J., Desponds, C., Conzelmann,
      A., and Ferguson, M. A. (1993) J. Biol. Chem. 268, 26365-26374). To determine in
      what subcellular compartment these side chains are made, we metabolically labeled
      GPI-anchored membrane proteins with myo-[2-3H]inositol in secretion mutants
      blocked at various stages of the secretory pathway and analyzed the anchor
      structure of the labeled glycoproteins. When the exit of vesicles from the
      endoplasmic reticulum or entry into the cis-Golgi were blocked in sec12 or sec18
      cells, all anchors contained a side chain consisting of a single alpha 1,2-linked
      mannose. GPI proteins trapped in the cis-Golgi of sec7 contained Man alpha 1,3Man
      alpha 1,2- but no Man alpha 1,2Man alpha 1,2-side chains. Mutants blocked at
      later stages of the secretory pathway made increased amounts of side chains
      containing two mannoses. Man alpha 1,2Man alpha 1,2- and Man alpha 1,3Man alpha
      1,2- side chains were preferentially associated with ceramide- and diacylglycerol
      containing GPI anchors, respectively. Mnn1, mnn2, mnn3, mnn5, and mnt1(=kre2),
      i.e. mutants which lack or down-regulate 1,2- and 1,3- mannosyltransferases used
      in the elongation of N- and O-glycans in the Golgi, add the fifth mannose to GPI
      anchors normally. The same conclusion was reached through the analysis of
      deletion mutants in KTR1, KTR2, KTR3, KTR4, and YUR1 which all are open reading
      frames with high homology to MNT1. Mutants deficient in the Golgi elongation of N
      glycans such as anp1, van1, mnn9 are deficient in the maturation of the N-glycans
      of GPI-anchored glycoproteins, but process the GPI anchor side chain normally.
      Data are consistent with the idea that the fourth mannose is added to proteins as
      part of the anchor precursor glycolipid in the endoplasmic reticulum, whereas the
      fifth mannose is added by not yet identified alpha 1,3- and alpha 1,2
      mannosyltransferases located in the Golgi apparatus.

PMID- 7649982
TI  - Analysis of the short consensus repeats of human complement factor B by site
      directed mutagenesis.
AB  - Human factor B is required for the initiation and propagation of the complement
      alternative pathway. It also participates in the amplification of the complement
      classical pathway. Alone, factor B is a zymogen with little known biochemical
      activity, but in the context of the alternative pathway convertases, the factor B
      serine protease is activated in a process that first involves the association
      with C3b and subsequently the cleavage of factor B into two fragments, Ba and Bb.
      Ba, the NH2-terminal fragment, is composed mainly of three tandem short consensus
      repeats, globular domains found in other complement proteins. It dissociates from
      the convertase during assembly, leaving the active C3 convertase, C3bBb. Previous
      reports suggest that the Ba region may be instrumental in convertase assembly.
      This hypothesis was tested using site-directed mutagenesis of recombinant factor
      B and monoclonal antibody epitope mapping to evaluate the relative importance of
      specific short consensus repeat amino acid residues. Three sites of interest were
      identified. Site 1 is a stretch of 19 contiguous amino acids in short consensus
      repeat 1 that form the epitope of a monoclonal antibody that effectively blocks
      factor B function. Site 2, composed of 6 contiguous amino acids in short
      consensus repeat 2, and site 3, consisting of 7 contiguous amino acids in short
      consensus repeat 3, were defined by mutations that reduce factor B hemolytic
      activity to 3% or less. Further analyses indicated that sites 2 and 3 contribute
      to factor B-C3b interactions.

PMID- 7649983
TI  - A library of monoclonal antibodies to Escherichia coli K-12 pyruvate
      dehydrogenase complex. A biochemical analysis and their ability to inhibit the
      enzyme complex.
AB  - A library of monoclonal antibodies to K-12 Escherichia coli pyruvate
      dehydrogenase complex (PDHc) and its pyruvate decarboxylating (EC 1.2.4.1; E1)
      subunit is reported. 21 monoclonal antibodies were generated, and 20 were
      investigated, of which 9 were elicited to PDHc and 11 to pure E1 subunit; 19 were
      of the IgG1 isotype and one of the IgG3 isotype. According to an enzyme
      immunoassay, all 20 of the monoclonal antibodies bound the PDHc, and 17 bound the
      E1 subunit. According to Western blot analysis, 14 of the 19 monoclonal
      antibodies bound to the E1 subunit. The monoclonal antibodies inhibited PDHc from
      0 to > 98%. The six monoclonal antibodies that displayed greater than 30%
      inhibition of E. coli PDHc were unable to inhibit porcine heart PDHc nor did they
      bind porcine heart PDHc according to dot blot analysis. Radiolabeling gave
      binding constants ranging from 5 to 10 x 10(8) M-1 on these six monoclonal
      antibodies, with greater than 80% of maximal inhibition achieved in less than 1
      min. One of the six, 18A9, gave > 98% inhibition, required two antibodies/E1
      subunit for maximum inhibition, and was shown to be a non-competitive inhibitor.
      Monoclonal antibody 15A9 was shown to counteract GTP-induced inhibition, while
      1F2 influenced the conformation of E1, allowing two antibodies, which did not
      previously bind E1, to bind to it. A new mechanism-based kinetic assay is
      presented that is specific for the E1 component of 2-keto acid dehydrogenases.
      This assay confirmed that the three most strongly inhibitory monoclonal
      antibodies specifically inhibited the E1 function while antibody 1F2 led to
      enhanced activity, suggesting an induced conformational change in PDHc or in E1.

PMID- 7649984
TI  - A library of monoclonal antibodies to Escherichia coli K-12 pyruvate
      dehydrogenase complex. Competitive epitope mapping studies.
AB  - Presented here are competitive epitope mapping studies on a monoclonal antibody
      library to K-12 Escherichia coli pyruvate dehydrogenase complex (PDHc) and its
      pyruvate decarboxylating (EC1.2.4.1) subunit (E1). Several of the monoclonal
      antibodies had been found to inhibit PDHc from 0 to 98%. Of the 10 monoclonal
      antibodies that showed the greatest inhibition of PDHc, 4 were elicited by PDHc
      and 6 by E1. Surface plasmon resonance was used for competitive epitope mapping
      and revealed that these 10 monoclonal antibodies had at least 6 separate binding
      regions on the PDHc. The three monoclonal antibodies that demonstrated the
      strongest inhibition appeared to bind the same region on the PDHc. Mapping
      studies with the E1 antigen using an additional five monoclonal antibodies
      demonstrated that the two strongest inhibitory monoclonal antibodies (18A9 and
      21C3) shared the same binding region on E1, whereas the third strongest inhibitor
      (15A9) displayed an epitope region that overlapped the previous two on the E1
      subunit. Antibody 15A9 had been shown to counteract GTP regulation of PDHc.
      Simultaneous multiple site binding experiments confirmed that the defined epitope
      regions were indeed independent. Limited competitive epitope binding experiments
      using radiolabeled E1 confirmed the surface plasmon resonance results.

PMID- 7649985
TI  - Four variant chicken erythroid AE1 anion exchangers. Role of the alternative N
      terminal sequences in intracellular targeting in transfected human
      erythroleukemia cells.
AB  - Four variant AE1 anion exchangers with predicted molecular masses of
      approximately 99, approximately 102, approximately 104, and approximately 108 kDa
      are expressed in chicken erythroid cells. These variant polypeptides differ in
      sequence only at the N terminus of their cytoplasmic domains. Molecular analyses
      have shown that transcripts derived from both of the erythroid-specific
      promoters, P1 and P2, encode all four of these AE1 anion exchanger variants.
      However, quantitative RNase protection analyses have shown that the transcripts
      derived from the P1 promoter are much more prevalent than those derived from the
      P2 promoter. Reverse transcriptase polymerase chain reaction studies have
      indicated that the extensive diversity in the transcripts derived from the AE1
      gene occurs both in primitive and definitive lineage erythroid cells. Transient
      transfection analyses using human erythroleukemia cells have investigated the
      functional significance of the alternative sequences at the N terminus of these
      variant exchangers. These studies have shown that the erythroid AE1 variants are
      sorted to different membrane compartments in these cells. The approximately 99-
      and approximately 102-kDa variants are primarily sorted to the plasma membrane,
      whereas the approximately 108-kDa variant is retained in a perinuclear
      compartment. These results suggest that the alternative N-terminal cytoplasmic
      sequences of these polypeptides may serve as signals to direct these variant
      transporters to different membrane compartments within cells.

PMID- 7649986
TI  - A metabolic enzyme that rapidly produces superoxide, fumarate reductase of
      Escherichia coli.
AB  - Aerobic organisms synthesize superoxide dismutases in order to escape injury from
      endogenous superoxide. An earlier study of Escherichia coli indicated that
      intracellular superoxide is formed primarily by autoxidation of components of the
      respiratory chain. In order to identify those components, inverted respiratory
      vesicles were incubated with five respiratory substrates. In most cases,
      essentially all of the superoxide was formed through autoxidation of fumarate
      reductase, despite the paucity of this anaerobic terminal oxidase in the aerobic
      cells from which the vesicles were prepared. In contrast, most dehydrogenases,
      the respiratory quinones, and the cytochrome oxidases did not produce any
      detectable superoxide. The propensity of fumarate reductase to generate
      superoxide could conceivably deluge cells with superoxide when anaerobic cells,
      which contain abundant fumarate reductase, enter an aerobic habitat. In fact,
      deletion or overexpression of the frd structural genes improved and retarded,
      respectively, the outgrowth of superoxide dismutase-attenuated cells when they
      were abruptly aerated, suggesting that fumarate reductase is a major source of
      superoxide in vivo. Steric inhibitors that bind adjacent to the flavin completely
      blocked superoxide production, indicating that the flavin, rather than an iron
      sulfur cluster, is the direct electron donor to oxygen. Since the turnover
      numbers for superoxide formation by other flavoenzymes are orders of magnitude
      lower than that of fumarate reductase (1600 min-1), additional steric or
      electronic factors must accelerate its autoxidation.

PMID- 7649987
TI  - Interaction of the ribosomal protein, L5, with protein phosphatase type 1.
AB  - The two-hybrid system was used to screen for binding proteins of type 1 protein
      phosphatase. Two plasmids were constructed, one containing the cDNA of the delta
      isoform of the type 1 catalytic subunit and the other containing a chicken
      gizzard cDNA library. Yeast (Y190) were transformed with the plasmids and
      screened for interacting species. 35 positive clones were categorized into 19
      gene groups. Most of these were not identified. One clone, however, contained a
      sequence identical to the C-terminal portion of the chicken ribosomal protein L5
      and corresponded to nucleotide residues 606-975. L5 was isolated from rat liver
      ribosomes as the L5.5 S RNA complex. This activated phosphatase activity of a
      myosin-bound phosphatase and the isolated type 1 catalytic subunit using
      phosphorylated myosin light chains and phosphorylase alpha as substrates. In
      addition, it was found that phosphatase sedimented with ribosomal subunits
      containing L5 but did not sediment with those deficient in L5. These data
      indicate that L5 binds to the catalytic subunit of the type 1 protein phosphatase
      and may act as a target molecule for phosphatase in ribosomal function or other
      cell mechanisms.

PMID- 7649988
TI  - The inhibitory effect of apolipoprotein E4 on neurite outgrowth is associated
      with microtubule depolymerization.
AB  - Evidence is presented for the differential effects of two isoforms of
      apolipoprotein (apo) E, apoE3 and apoE4, on neurite outgrowth and on the
      cytoskeleton of neuronal cells (Neuro-2a) in culture. In the presence of a lipid
      source, apoE3 enhances and apoE4 inhibits neurite outgrowth. Immunocytochemical
      studies demonstrate that there is a higher concentration of apoE3 than apoE4 in
      both the cell bodies and neurites. Cells treated with apoE4 showed fewer
      microtubules and a greatly reduced ratio of polymerized to monomeric tubulin than
      did cells treated with apoE3. The effect of apoE4 on depolymerization of
      microtubules was shown by biochemical, immunocytochemical, and ultrastructural
      studies. The depolymerization of microtubules and the inhibition of neurite
      outgrowth associated with apoE4 suggest a mechanism whereby apoE4, which has been
      linked to the pathogenesis of Alzheimer's disease, may prevent normal neuronal
      remodeling from occurring later in life, when this neurodegenerative disorder
      develops.

PMID- 7649989
TI  - Heavy chain dimers as well as complete antibodies are efficiently formed and
      secreted from Drosophila via a BiP-mediated pathway.
AB  - We have constructed a stable Drosophila cell line co-expressing heavy chain (HC)
      and light chain (LC) immunoglobulins of a humanized monoclonal antibody (mAb)
      that recognizes the F antigen of respiratory syncytial virus (Tempest, P. R.,
      Bremmer, P., Lambert, M., Taylor, G., Furze, J. M., Carr, F. J., and Harris, W.
      J. (1991) Bio/Technology 9, 266-271. These cells efficiently secrete antibody
      with substrate binding activity indistinguishable from that produced from
      vertebrate cell lines. Significantly, the Drosophila homologue of the
      immunoglobulin binding chaperone protein (BiP), hsc72, was found to interact
      specifically with the immunoglobulin HC in an ATP-dependent fashion, similar to
      the BiP-HC interaction known to occur in vertebrate cells. This is, in fact, the
      first substrate ever shown to interact specifically with Drosophila hsc72. Most
      surprisingly, expression of heavy chains in the absence of LC led to the
      efficient secretion of heavy chain dimers. Moreover, this secretion occurred in
      association with hsc72. This dramatically contrasts with what is seen in
      vertebrate cells where in the absence of LC, HC remains sequestered inside the
      cell in stable association with BiP. Our results clearly suggest that Drosophila
      BiP can substitute for its mammalian counterpart and chaperone the secretion of
      active IgG. However, the finding that Drosophila BiP can also uniquely chaperone
      heavy chain dimers indicates mechanistic differences that may relate to the
      evolved need for retaining immature IgGs in vertebrates.

PMID- 7649990
TI  - Limitations of the mass isotopomer distribution analysis of glucose to study
      gluconeogenesis. Substrate cycling between glycerol and triose phosphates in
      liver.
AB  - Mass isotopomer distribution analysis allows studying the synthesis of polymeric
      biomolecules from 15N, 13C-, or 2H-labeled monomeric units in the presence of
      unlabeled polymer. The mass isotopomer distribution of the polymer allows
      calculation of (i) the enrichment of the monomer and (ii) the dilution of the
      newly synthesized polymer by unlabeled polymer. We tested the conditions of
      validity of mass isotopomer distribution analysis of glucose labeled from [U
      13C3]lactate, [U-13C3]glycerol, and [2-13C]glycerol to calculate the fraction of
      glucose production derived from gluconeogenesis. Experiments were conducted in
      perfused rat livers, live rats, and live monkeys. In all cases, [13C]glycerol
      yielded labeling patterns of glucose that are incompatible with glucose being
      formed from a single pool of triose phosphates of constant enrichment. We show
      evidence that variations in the enrichment of triose phosphates result from (i)
      the large fractional decrease in physiological glycerol concentration in a single
      pass through the liver and (ii) the release of unlabeled glycerol by the liver,
      presumably via lipase activity. This zonation of glycerol metabolism in liver
      results in the calculation of artifactually low contributions of gluconeogenesis
      to glucose production when the latter is labeled from [13C]glycerol. In contrast,
      [U-13C3]lactate appears to be a suitable tracer for mass isotopomer distribution
      analysis of gluconeogenesis in vivo, but not in the perfused liver. In other
      perfusion experiments with [2H5]glycerol, we showed that the rat liver releases
      glycerol molecules containing one to four 2H atoms. This indicates the operation
      of a substrate cycle between extracellular glycerol and liver triose phosphates,
      where 2H is lost in the reversible reactions catalyzed by alpha-glycerophosphate
      dehydrogenase, triose-phosphate isomerase, and glycolytic enzymes. This substrate
      cycle presumably involves alpha-glycerophosphate hydrolysis.

PMID- 7649991
TI  - Kinetic analysis of the folding of human growth hormone. Influence of disulfide
      bonds.
AB  - We report the results of a stopped-flow kinetic evaluation of the folding of
      human growth hormone (hGH). The results are compared with those obtained for a
      disulfide-modified analog in which the four cysteine residues have been reduced
      and alkylated to form tetra-S-carbamidomethylated hGH in order to elucidate the
      role of disulfide bonds in the folding reaction. Multiple detection techniques
      were applied to monitor both refolding and unfolding processes initiated by
      guanidine hydrochloride concentration jumps. Using far-UV circular dichroism (CD)
      detection to monitor folding of hGH, we find that 70% of the secondary structure
      forms in a burst phase occurring within the stopped-flow dead time. Two slower
      phases were identified in the observable portion of the CD signal. Multiple
      kinetic phases were resolved when folding was monitored by intrinsic tryptophan
      fluorescence or near-UV absorbance as probes of tertiary structure, and the
      number of time constants required to fit the data depended on the hGH
      concentration and nature of the denaturant jump. The associated amplitudes also
      displayed strong dependence on the final denaturant concentration. Results
      obtained from the tetra-S-carbamidomethylated hGH studies demonstrate that the
      folding reactions of hGH are remarkably similar in the presence and absence of
      the disulfide bonds. Disulfide bond reduction in hGH is proposed to affect
      folding primarily by increasing the population of self-associated intermediate
      states in the folding pathway.

PMID- 7649992
TI  - A mutant Bradyrhizobium japonicum delta-aminolevulinic acid dehydratase with an
      altered metal requirement functions in situ for tetrapyrrole synthesis in soybean
      root nodules.
AB  - The tetrapyrrole synthesis enzyme delta-aminolevulinic acid (ALA) dehydratase
      requires Mg2+ for catalytic activity in photosynthetic organisms and in
      Bradyrhizobium japonicum, a bacterium that can reside symbiotically within plant
      cells of soybean root nodules or as a free-living organism. ALA dehydratase from
      animals and other non-photosynthetic organisms is a Zn(2+)-dependent enzyme. A
      modified B. japonicum ALA dehydratase, ALAD*, was constructed by site-directed
      mutagenesis of hemB in which three proximal amino acids conserved in plant
      dehydratases were changed to cysteine residues as is found in the Zn(2+)
      dependent enzyme of animals. These substitutions resulted in an enzyme that
      required Zn2+ rather than Mg2+ for catalytic activity, and therefore a region of
      the ALA dehydratase from B. japonicum, and probably from plants, was identified
      that is involved in Mg2+ dependence. In addition, the data show that a change in
      only a few residues is sufficient to change a Mg(2+)-dependent ALA dehydratase to
      a Zn(2+)-dependent one. B. japonicum strains were constructed that contained a
      single copy of either hemB or the altered gene hemB* integrated into the genome
      of a hemB- mutant. Cultures of the hemB* strain KPZn3 had Zn(2+)-dependent ALA
      dehydratase activity that functioned in vivo as discerned by its heme prototrophy
      and expression of wild type levels of cellular hemes. Strain KPZn3 elicited root
      nodules on soybean that contained viable bacteria and exhibited traits of
      normally developed nodules, and the symbiotic bacteria expressed nearly wild type
      levels of cellular hemes. We conclude that the Zn(2+)-dependent ALAD* can
      function and support bacterial tetrapyrrole synthesis within the plant milieu of
      root nodules.

PMID- 7649993
TI  - Mitogen-activated protein kinase activation requires two signal inputs from the
      human anaphylatoxin C5a receptor.
AB  - The anaphylatoxin C5a receptor activates the Ras/Raf/mitogen-activated protein
      (MAP) kinase pathway in human neutrophils. The signal pathways involved in
      Ras/Raf/MAP kinase activation in response to C5a and other chemoattractant
      receptors is poorly understood. Stimulation of the C5a receptor expressed in
      HEK293 cells results in modest MAP kinase activation, which is inhibited by
      pertussis toxin-catalyzed ADP-ribosylation of G(i). Coexpression of the C5a
      receptor and the G16 alpha subunit (alpha 16) results in the G16-mediated
      activation of phospholipase C beta and a robust MAP kinase activation. Pertussis
      toxin treatment of C5a receptor/alpha 16-cotransfected cells inhibits C5a
      stimulation of MAP kinase activity approximately 60% relative to the control
      response. Similarly, the protein kinase C inhibitor, GF109203X inhibits
      activation of MAP kinase activation in C5a receptor/alpha 16-cotransfected cells
      by 60%; the protein kinase C inhibitor does not affect the modest C5a receptor
      response in the absence of alpha 16 expression. These results demonstrate that
      two independent signals are required for the maximal activation of MAP kinase by
      G protein-coupled receptors.

PMID- 7649994
TI  - Dietary fat elevates hepatic apoA-I production by increasing the fraction of
      apolipoprotein A-I mRNA in the translating pool.
AB  - Elevated plasma high density lipoprotein cholesterol (HDL-C) levels are
      associated with a decreased risk for coronary heart disease. Ironically, diets
      enriched in saturated fat and cholesterol (HF/HC diets), which tend to accelerate
      atherosclerotic processes by increasing LDL cholesterol levels, also raise HDL-C.
      We have recently reported, using a human apoA-I (hapoA-1) transgenic mouse model,
      that the elevation of HDL-C by a HF/HC diet is attributable, in part, to an
      increase in the hepatic production of hapoA-1. To further define the
      hepatocellular processes associated with this induction, we have prepared primary
      hepatocytes from hapoA-1 transgenic mice. Rates of hapoA-1 secretion were 40%
      greater from cells prepared from animals fed the HF/HC relative to a low fat-low
      cholesterol (LF/LC) control diet. The abundance of hapoA-1 mRNA in these cells
      was similar between hepatocytes prepared from the HF/HC and LF/LC diet fed
      animals, suggesting a post-transcriptional mechanism that does not involve mRNA
      stability. Inhibition of secretion using brefeldin A revealed an increase in
      cellular hapoA-1 accumulation. Thus, the HF/HC diet apparently affects hepatic
      hapoA-1 production via a mechanism that is manifest prior to the exit of newly
      synthesized hapoA-1 from the Golgi. Pulse-chase experiments revealed a 39%
      greater peak hapoA-1 synthesis, with no difference in the degradation of total
      labeled hapoA-1 protein, as a result of the HF/HC diet feeding. Finally,
      resolution of liver S10 extracts via sucrose density sedimentation and
      metrizamide density equilibrium gradient centrifugation analyses both revealed
      similar increases (31 and 24%, respectively) in the relative percentage of hapoA
      1 mRNA associated with the translating polysomal fractions as a result of the
      HF/HC feeding. Together, these data suggest that the HF/HC diet affects hepatic
      hapoA-1 production via a specific modulation in the relative amount of hapoA-1
      mRNA in the polysomal pool. These observations provide an opportunity to explore
      a new mechanism regulating apoA-1 production and might lead to the development of
      novel therapies to elevate plasma HDL-C levels.

PMID- 7649995
TI  - Hsc70-binding peptides selected from a phage display peptide library that
      resemble organellar targeting sequences.
AB  - A 15-mer phage display random peptide library was screened with purified bovine
      Hsc70, and nucleotide sequence analysis of the selected clones showed a large
      enrichment for peptides containing basic sequences with at least KK, KR, or RR.
      Binding affinity for Hsc70 of representative peptides increased dramatically for
      heptamers compared with hexamers. The peptide NIVRKKK had the highest affinity
      for Hsc70, and substitution analyses showed that hydrophobic residues followed by
      basic residues play important roles in maintaining this affinity. In contrast,
      NIVRKKK was a weaker stimulator of the Hsc70 ATPase activity compared with pigeon
      cytochrome c peptide and FYQLALT, a peptide optimized for binding to Hsc70.
      FYQLALT effectively blocked the binding of NIVRKKK to Hsc70, possibly by causing
      a conformational change that masked Hsc70's binding site for the basic peptide.
      Two hypotheses are offered to explain the two different peptide motifs. First, it
      is proposed that Hsc70 recognizes two different amino acid sequence motifs in its
      dual roles of chaperoning proteins to organelles (NIVRKKK-like sequences) and
      facilitating protein folding (FYQLALT-like sequences). Second, the NIVRKKK motif
      may be used to bind certain folded proteins with which Hsc70 interacts, such as
      itself, p53, and Dnaj2.

PMID- 7649996
TI  - Metabolism of 6-trans-isomers of leukotriene B4 in cultured hepatoma cells and in
      human polymorphonuclear leukocytes. Identification of a delta 6-reductase
      metabolic pathway.
AB  - The intermediate metabolic events which degrade hydroxy polyunsaturated fatty
      acids is largely unknown. Such molecules are common products of lipid
      peroxidation and lipoxygenase catalyzed oxidation of arachidonic acid. Metabolism
      of two 5,12-dihydroxyeicosatetraenoic acids, 6-trans-LTB4 (leukotriene B4), and 6
      trans-12-epi-LTB4 was studied in HepG2 cells (a human-derived hepatoma cell
      line). Extensive metabolism was observed with a major metabolite identified as 4
      hydroxy-6-dodecenoic acid for both epimers. Incubation of 6-trans-LTB4 epimers at
      shorter times revealed the formation of intermediate metabolites, including 6
      hydroxy-4,8-tetradecadienoic acid and 8-hydroxy-4,6,10-hexadecatrienoic acid
      suggesting beta-oxidation as the major pathway leading to the formation of the
      common terminal metabolite. Two additional metabolites were structurally
      elucidated as 5-oxo-6,7-dihydro-LTB4 and 6,7-dihydro-LTB4 which have not been
      previously described. Formation of 5-oxo-6,7-dihydro-LTB4 and 6,7-dihydro-LTB4
      were also observed during metabolism of 6-trans-12-epi-LTB4 in human
      polymorphonuclear leukocytes. Of particular interest is the metabolism of these
      compounds by beta-oxidation from the carboxyl terminus, a process which is not
      observed with leukotriene B4 or leukotriene C4. Identification of these
      metabolites suggested the operation of the 5-hydroxyeicosanoid dehydrogenase
      pathway followed by a delta 6-reductase metabolic pathway which has not been
      previously described. This pathway of beta-oxidation may limit the activity of
      various 5,12-diHETEs including nonenzymatic hydrolysis products of LTA4 and also
      the recently described B4-isoleukotrienes.

PMID- 7649997
TI  - Reconstitution of Escherichia coli RNase HI from the N-fragment with high
      helicity and the C-fragment with a disordered structure.
AB  - The Escherichia coli RNase HI variant with the Lys86-->Ala mutation is purified
      in two forms, as nicked and intact proteins. The nicked K86A protein, in which
      the N-fragment (Met1-Lys87) and the C-fragment (Arg88-Val155) remain associated,
      is enzymatically active. These N- and C-fragments were isolated and examined for
      reassociation. These peptides did not associate to form the nicked K86A protein
      at pH 3.0 in the absence of salt, but were associated, with a yield of 30-80%,
      when the pH was raised to 5.5 or when salt was added. Measurements of the CD
      spectra show that the alpha-helices are partially formed in the N-fragment at pH
      3.0 in the absence of salt and are almost fully formed either at pH 5.5 or at pH
      3.0 in the presence of 0.15 M NaCl. In contrast, the C-fragment remains almost
      fully disordered under these conditions. The N-fragment with this high (native
      like) helicity shows the characteristics of a molten globule with respect to the
      content of the secondary and tertiary structures, the ability to bind a
      fluorescent probe (1-anilinonaphthalene-8-sulfonic acid), and the behavior on the
      thermal transition. These results suggest that the N-fragment contains an initial
      folding site, probably the alpha I-helix, and the completion of the folding in
      this site provides a surface that facilitates the folding of the C-fragment. This
      folding process may represent that of the intact RNase HI molecule.

PMID- 7649998
TI  - Expression and characterization of branched-chain alpha-ketoacid dehydrogenase
      kinase from the rat. Is it a histidine-protein kinase?
AB  - The recombinant rat branched-chain alpha-ketoacid dehydrogenase kinase has been
      amplified from rat kidney cDNA, based on the previously reported rat cDNA
      sequence (Popov, K. M., Zhao, Y., Shimomura, Y., Kuntz, M. J., and Harris, R. A.
      (1992) J. Biol. Chem. 267, 13127-13130). This kinase was expressed in Escherichia
      coli as a fusion protein with bacterial maltose-binding protein (MBP). Expression
      was improved by overexpression of chaperonins GroEL and GroES. The MBP-kinase,
      when reconstituted with lipoylated recombinant E2 (dihydrolipoyl transacylase),
      catalyzed phosphorylation of recombinant E1 (branched-chain alpha-ketoacid
      decarboxylase) with a kcat of 28.5 nmol of phosphate/min/nmol of MBP-kinase at 25
      degrees C. Recombinant MBP-kinase alone demonstrated a slow rate of
      autophosphorylation with a kcat of 3.25 pmol of phosphate/min/nmol of kinase at
      25 degrees C. Serine 22 of the kinase was identified as the possible site of
      autophosphorylation by Edman microsequencing analysis. Autophosphorylated kinase
      cannot transfer phosphate to E1, indicating that autophosphorylation of kinase is
      not an intermediate in ATP-dependent phosphorylation of E1. Therefore, despite
      the reported sequence similarity to prokaryotic histidine protein kinases, the
      mitochondrial rat branched-chain alpha-ketoacid dehydrogenase kinase apparently
      does not phosphorylate E1 via a histidine-mediated phosphotransfer reaction.
      Significant corrections to the published cDNA sequence of rat branched-chain
      alpha-ketoacid dehydrogenase kinase are included.

PMID- 7649999
TI  - Characterization of the effector-specifying domain of Rac involved in NADPH
      oxidase activation.
AB  - Production of microbicidal oxidants by phagocytic leukocytes requires activation
      of a latent NADPH oxidase by the coordinated assembly of a membrane-associated
      flavocytochrome b558, with three cytosolic components, p47phox, p67phox, and the
      low molecular weight GTP-binding protein Rac. Rac1 and Rac2 have 92% sequence
      identity and are both active in supporting the oxidase, while CDC42Hs, the
      closest relative to Rac with 70% sequence identity, only weakly supports oxidase
      activation in vitro. We have used CDC42Hs as a foil to identify residues in Rac
      that are critical for oxidase activation. Most of the divergent sequences of
      CDC42Hs could be incorporated into Rac-CDC42Hs chimeric proteins without
      affecting cell-free NADPH oxidase activity. However, incorporation of the amino
      terminal segment of CDC42Hs (residues 1-40), which differs from Rac1 by only four
      residues (positions 3, 27, 30, and 33), resulted in a marked loss of oxidase
      activation capacity. Point mutagenesis studies showed that this was due to
      changes at residues 27 and 30, but not residues 3 and 33. Conversely,
      incorporation of the amino terminus of Rac1 (residues 1-40) into CDC42Hs
      increased its activity to that of Rac1, indicating that this terminus contains
      the effector-specifying domain of Rac. Taken together, these studies show that
      the difference in the activity between CDC42Hs and Rac1 is due entirely to
      differences in amino acids at position 27 and 30.

PMID- 7650000
TI  - Signal sequence processing in rough microsomes.
AB  - Secretory proteins are synthesized with a signal sequence that is usually cleaved
      from the nascent protein during the translocation of the polypeptide chain into
      the lumen of the endoplasmic reticulum. To determine the fate of a cleaved signal
      sequence, we used a synchronized in vitro translocation system. We found that the
      cleaved signal peptide of preprolactin is further processed close to its COOH
      terminus. The resulting fragment accumulated in the microsomal fraction and with
      time was released into the cytosol. Signal sequence cleavage and processing could
      be reproduced with reconstituted vesicles containing Sec61, signal recognition
      particle receptor, and signal peptidase complex.

PMID- 7650002
TI  - Rapid refolding studies on the chaperone-like alpha-crystallin. Effect of alpha
      crystallin on refolding of beta- and gamma-crystallins.
AB  - alpha-Crystallin, a multimeric protein present in the eye lens, is shown to have
      chaperone-like activity in preventing thermally induced aggregation of enzymes
      and other crystallins. We have studied the rapid refolding of alpha-crystallin,
      and compared it with other calf eye lens proteins, namely beta- and gamma
      crystallins. alpha-Crystallin forms a clear solution upon rapid refolding from 8
      M urea. The refolded alpha-crystallin has native-like secondary, tertiary, and
      quaternary structures as revealed by circular dichroism and fluorescence
      characteristics as well as gel filtration and sedimentation velocity
      measurements. On rapid refolding, beta- and gamma-crystallins aggregate and form
      turbid solutions. The presence of alpha-crystallin in the refolding buffer
      marginally increases the recovery of beta- and gamma-crystallins in the soluble
      form. However, unfolding of these crystallins together with alpha-crystallin
      using 8 M urea and subsequent refolding significantly increases the recovery of
      these proteins in the soluble form. These results indicate that an intermediate
      of alpha-crystallin formed during refolding is more effective in preventing the
      aggregation of beta- and gamma-crystallins. This supports our earlier hypothesis
      (Raman, B., and Rao, C. M. (1994) J. Biol. Chem. 269, 27264-27268) that the
      chaperone-like activity of alpha-crystallin is more pronounced in its
      structurally perturbed state.

PMID- 7650001
TI  - The myristoyl moiety of myristoylated alanine-rich C kinase substrate (MARCKS)
      and MARCKS-related protein is embedded in the membrane.
AB  - Members of the myristoylated alanine-rich protein kinase C substrate (MARCKS)
      family are involved in several cellular processes such as secretion, motility,
      mitosis, and transformation. In addition to their ability to bind calmodulin and
      to cross-link actin filaments, reversible binding to the plasma membrane is most
      certainly an important component of the so far unknown functions of these
      proteins. We have therefore investigated the binding of murine MARCKS-related
      protein (MRP) to lipid vesicles. The partition coefficient, Kp, describing the
      affinity of myristoylated MRP for acidic lipid vesicles (20% phosphatidylserine,
      80% phosphatidylcholine) is 5-8 x 10(3) M-1, which is only 2-4 times larger than
      the partition coefficient for the unmyristoylated protein. Interestingly, the
      affinity of MRP for acidic lipid membranes is 20-30-fold smaller than reported
      for murine MARCKS (Kim, J., Shishido, T., Jiang, X., Aderem, A. A., and
      McLaughlin, S. (1994) J. Biol. Chem. 269, 28214-28219). Since only a marginal
      binding could be observed with neutral phosphatidylcholine vesicles, we propose
      that electrostatic interactions are the major determinant of the binding of MRP
      to pure lipid membranes. Although the myristoyl moiety does not contribute
      drastically to the binding of MRP to vesicles, photolabeling experiments with a
      photoreactive phospholipid probe show that the fatty acid is embedded in the
      bilayer. The same membrane topology was found for bovine brain MARCKS. Since the
      relatively low affinity of MRP for vesicles is insufficient to account for a
      stable anchoring of the protein to cellular membranes, insertion of the myristoyl
      moiety into the bilayer might favor the interaction of MRP with additional
      factors required for the binding of the protein to intracellular membranes.

PMID- 7650003
TI  - Ligand recognition properties of the Escherichia coli 4-aminobutyrate transporter
      encoded by gabP. Specificity of Gab permease for heterocyclic inhibitors.
AB  - 4-aminobutyrate metabolism in Escherichia coli begins with transport across the
      cytoplasmic membrane via the GabP, which is encoded by gabP. Although GabP is
      specific and exhibits poor affinity for many cellular constituents such as the
      alpha-amino acids, the range of compounds recognized with high affinity has yet
      to be investigated. In order to address this gap in knowledge, we developed a
      gabP-negative host strain, which permits evaluation of test compounds for
      inhibitory effects on cloned GabP (expression inducible by isopropyl-1-thio-beta
      D-galactopyranoside). Using this inducible expression system, three structurally
      distinct categories of high affinity transport inhibitor were identified. The
      structural dissimilarity of these inhibitors significantly alters our view of
      ligand recognition by GabP. Any complete model must now account for the
      observation that inhibition of 4-aminobutyrate transport can be mediated either
      (i) by open chain analogs of 4-aminobutyrate, (ii) by cyclic amino acid analogs,
      or (iii) by planar heterocyclic compounds lacking a carboxyl group. Such results
      do not support a previously sustainable view of GabP that features a restrictive
      ligand recognition domain, unable to accommodate structures that differ very much
      from the native substrate, 4-aminobutyrate.

PMID- 7650004
TI  - NFATc3, a lymphoid-specific NFATc family member that is calcium-regulated and
      exhibits distinct DNA binding specificity.
AB  - Signals transduced by the T cell antigen receptor (TCR) regulate developmental
      transitions in the thymus and also mediate the immunologic activation of mature,
      peripheral T cells. In both cases TCR stimulation leads to the assembly of the
      NFAT transcription complex as a result of the calcium-dependent nuclear
      translocation of cytosolic subunits, NFATc, and the Ras/protein kinase C
      dependent induction of a nuclear subunit, NFATn. To further understand the
      diverse roles of antigen receptor signaling throughout T cell development, we
      have identified a new NFATc family member, NFATc3, that is expressed at highest
      levels in the thymus. NFATc3 is the product of a gene on murine chromosome 8 that
      is not linked to the other NFATc genes. NFATc3, like other NFATc family members,
      contains a conserved rel similarity domain, and also defines a region conserved
      among NFATc family members, the SP repeat region, characterized by the repeated
      motif SPxxSPxxSPrxsxx (D/E)(D/E)swl. NFATc3 activates NFAT site-dependent
      transcription when overexpressed, yet exhibits a pattern of DNA site specificity
      distinct from other NFATc proteins. Additionally, thymic NFATc3 undergoes
      modifications in response to agents that mimic T cell receptor signaling,
      including a decrease in apparent molecular mass upon elevation of intracellular
      calcium that is inhibited by the immunosuppressant FK506. Given the preferential
      expression of NFATc3 in the thymus, NFATc family members may regulate distinct
      subsets of genes during T cell development.

PMID- 7650005
TI  - Histamine antagonizes serotonin and growth factor-induced mitogen-activated
      protein kinase activation in bovine tracheal smooth muscle cells.
AB  - We examined the effects of the bronchoconstrictor agonists serotonin (5
      hydroxytryptamine; 5-HT) and histamine on mitogen-activated protein (MAP) kinase
      activation in cultured bovine tracheal myocytes. Kinase renaturation assays
      demonstrated activation of the 42- and 44-kDa MAP kinases within 2 min of 5-HT
      exposure. MAP kinase activation was mimicked by alpha-methyl-5-HT and reduced by
      pretreatment with either phorbol 12,13-dibutyrate or forskolin, suggesting
      activation of the 5-HT2 receptor, protein kinase C, and Raf-1, respectively. Raf
      1 activation was confirmed by measurement of Raf-1 activity, and the requirement
      of Raf-1 for 5-HT-induced MAP kinase activation was demonstrated by transient
      transfection of cells with a dominant-negative allele of Raf-1. Histamine
      pretreatment significantly inhibited 5-HT and insulin-derived growth factor-1
      induced MAP kinase activation. Attenuation of MAP kinase activation was reversed
      by cimetidine, mimicked by forskolin, and accompanied by cAMP accumulation and
      inhibition of Raf-1, suggesting activation of the H2 receptor and cAMP-dependent
      protein kinase A. However, histamine treatment inhibited Raf-1 but not MAP kinase
      activation following treatment with either platelet-derived growth factor or
      epidermal growth factor, implying a Raf-1-independent MAP kinase activation
      pathway. In summary, our data suggest a model whereby 5-HT activates MAP kinase
      via a protein kinase C/Raf-1 pathway, and histamine attenuates MAP kinase
      activation by serotonin via activation of cAMP-dependent protein kinase A and
      inhibition of Raf-1.

PMID- 7650006
TI  - Muscle creatine kinase-deficient mice. I. Alterations in myofibrillar function.
AB  - The regulation of contractile activity in mice bearing a null mutation of the M
      isoform of creatine kinase gene, has been investigated in tissue extracts and
      Triton X-100-treated preparations of ventricular, soleus, and gastrocnemius
      muscles of control and transgenic mice. Skinned fiber experiments did not
      evidence any statistical difference in the maximal force or the calcium
      sensitivity of either muscle type. Rigor tension development at a low MgATP
      concentration was greatly influenced by phosphocreatine in control but not in
      transgenic mice as should be expected. In calcium-activated ventricular
      preparations, although the force developed by each cross-bridge was the same in
      control and transgenic animals, the rate constant of tension changes appeared to
      be markedly slowed in transgenic animals. As the ventricular isomyosin pattern
      was not altered, we suggested that, in transgenic animals, cross-bridge cycling
      was hindered by a local decrease in the MgATP to MgADP ratio, due to lack of a
      local MgATP regenerating system. Myokinase activity was not significantly changed
      while activities of pyruvate kinase or glyceraldehyde-3-phosphate dehydrogenase
      were found to be increased in transgenic animals. These results show that no
      fundamental remodelling occurs in myofibrils of transgenic animals but that
      important adaptations modify the bioenergetic pathways including glycolytic
      metabolism.

PMID- 7650007
TI  - Muscle creatine kinase-deficient mice. II. Cardiac and skeletal muscles exhibit
      tissue-specific adaptation of the mitochondrial function.
AB  - Functional properties of in situ mitochondria and of mitochondrial creatine
      kinase were studied in saponin-skinned fibers taken from normal and M-creatine
      kinase-deficient mice. In control animals, apparent Km values of mitochondrial
      respiration for ADP in cardiac (ventricular) and slow-twitch (soleus) muscles
      (137 +/- 16 microM and 209 +/- 10 microM, respectively) were manyfold higher than
      that in fast-twitch (gastrocnemius) muscle (7.5 +/- 0.5 microM). Creatine
      substantially decreased the Km values only in cardiac and slow-twitch muscles (73
      +/- 11 microM and 131 +/- 21 microM, respectively). As compared to control, in
      situ mitochondria in transgenic ventricular and slow-twitch muscles showed two
      times lower Km values for ADP, and the presence of creatine only slightly
      decreased the Km values. In mutant fast-twitch muscle, a decrease rather than
      increase in mitochondrial sensitivity to ADP occurred, but creatine still had no
      effect. Furthermore, in these muscles, relatively low oxidative capacity was
      considerably elevated. It is suggested that in the mutant mice, impairment of
      energy transport function in ventricular and slow-twitch muscles is compensated
      by a facilitation of adenine nucleotide transportation between mitochondria and
      cellular ATPases; in fast-twitch muscle, mainly energy buffering function is
      depressed, and that is overcome by an increase in energy-producing potential.

PMID- 7650008
TI  - The precursor of pea ferredoxin-NADP+ reductase synthesized in Escherichia coli
      contains bound FAD and is transported into chloroplasts.
AB  - The precursor of the chloroplast flavoprotein ferredoxin-NADP+ reductase from pea
      was expressed in Escherichia coli as a carboxyl-terminal fusion to glutathione S
      transferase. The fused protein was soluble, and the precursor could be purified
      in a few steps involving affinity chromatography on glutathione-agarose, cleavage
      of the transferase portion by protease Xa, and ion exchange chromatography on
      DEAE-cellulose. The purified prereductase contained bound FAD but displayed
      marginally low levels of activity. Removal of the transit peptide by limited
      proteolysis rendered a functional protease-resistant core exhibiting enzymatic
      activity. The FAD-containing precursor expressed in E. coli was readily
      transported into isolated pea chloroplasts and was processed to the mature size,
      both inside the plastid and by incubation with stromal extracts in a plastid-free
      reaction. Import was dependent on the presence of ATP and was stimulated
      severalfold by the addition of plant leaf extracts.

PMID- 7650009
TI  - Role of calcium feedback in excitation-contraction coupling in isolated triads.
AB  - There is a considerable controversy in the literature concerning the effects of
      higher concentrations of calcium chelators (e.g. BAPTA (1,2-bis(o
      aminophenoxy)ethane-N,N,N',N'-tetraacetic acid) or fura-2) on the intracellular
      Ca2+ transients in muscle. We induced calcium release from sarcoplasmic reticulum
      (SR) in the triad preparation by chemical depolarization of the T-tubule in the
      presence of various concentrations of BAPTA-calcium buffer ([Ca2+] = 0.1 microM)
      and investigated the effects of the BAPTA concentration on the time courses of
      conformational changes in the junctional foot protein (JFP) and calcium release
      from SR. Upon stimulation, the JFP underwent biphasic conformational changes, as
      determined by stopped-flow fluorometry of the JFP-bound conformational probe. The
      first phase of protein conformational change, which preceded calcium release from
      SR, was virtually unaffected by the BAPTA concentration. However, the magnitude
      of the second phase increased in an inversely proportional fashion to the BAPTA
      concentration. An abrupt increase in [Ca2+] from 0.1 microM up to 1.0 microM
      (delta Ca2+), concurrently with T-tubule depolarization, produced biphasic
      protein conformational changes: a delta Ca(2+)-independent first phase and a
      delta Ca(2+)-dependent second phase. Similar Ca2+ jump experiments under non
      depolarizing conditions produced a slow monophasic conformational change
      equivalent to the second phase described above. These results suggest that the
      first phase of protein conformational change represents the activation of JFP by
      T-tubule depolarization to induce calcium release, and the second phase the
      secondary activation by the released Ca2+. Activation of the JFP by the released
      Ca2+ resulted in an acceleration of both (i) the rate of initial calcium release,
      and (ii) the subsequent attenuation of calcium release. The acceleration of both
      was suppressed by higher concentrations of BAPTA. These results provide a
      reasonable explanation for both of the apparently contradictory views in the
      literature; high concentrations of calcium buffer (a) suppress the initial
      activation and (b) prevent the subsequent attenuation of calcium release.

PMID- 7650010
TI  - Rapid and persistent desensitization of m3 muscarinic acetylcholine receptor
      stimulated phospholipase D. Concomitant sensitization of phospholipase C.
AB  - Activation of muscarinic acetylcholine receptors (mAChR) in human embryonic
      kidney (HEK) cells stably expressing the human m3 subtype leads to stimulation of
      both phospholipase C (PLC) and D (PLD). mAChR-stimulated PLD was turned off after
      2 min of receptor activation with either the full (carbachol) or partial agonist
      (pilocarpine) and remained completely suppressed for at least 4 h. Partial
      recovery was observed 24 h after agonist removal. This rapid arrest of PLD
      response was not due to a loss of cell surface receptors and was also not caused
      by negative feedback due to concomitant activation of protein kinase C, tyrosine
      phosphorylation, increase in cytosolic calcium, or activation of Gi proteins.
      Furthermore, PLD stimulation by directly activated protein kinase C and GTP
      binding proteins was unaltered in carbachol-pretreated cells. Finally, neither
      prevention of PLD stimulation during carbachol pretreatment by genistein nor
      inhibition of protein synthesis by cycloheximide, added before or after carbachol
      challenge, resulted in recovery of mAChR-stimulated PLD. The short term carbachol
      pretreatment nearly completely abolished agonist-induced binding of guanosine 5'
      O-(3-thiotriphosphate) to membranes or permeabilized adherent cells. Full
      recovery of this response was achieved after 4 h. Similar to transfected m3
      mAChR, PLD stimulation by endogenously expressed purinergic receptors was also
      fully blunted after 2 min of agonist (ATP) treatment. Preexposure of HEK cells to
      either receptor agonist partially, but not completely, reduced PLD stimulation by
      the other agonist. In contrast to desensitization of PLD stimulation, 2 min of
      carbachol treatment led to a sensitization, by up to 2-fold, of mAChR-stimulated
      inositol phosphate formation. This supersensitivity was also observed with
      pilocarpine, which acted as a full agonist on PLC. On the basis of these results,
      we conclude that the m3 mAChR stimulates PLD and PLC in HEK cells with distinct
      efficiencies and with very distinct durations of each response. The rapid and
      long lasting desensitization of the PLD response is apparently not due to a loss
      of cell surface receptors or PLD activation by GTP-binding proteins, but it may
      involve, at least initially, an uncoupling of receptors from GTP-binding proteins
      and most likely a loss of an as yet undefined essential transducing component.

PMID- 7650011
TI  - Kinetic analysis of interactions between GroEL and reduced alpha-lactalbumin.
      Effect of GroES and nucleotides.
AB  - The real-time analysis of the association and dissociation of chaperonin with
      respect to its substrate protein was carried out using the BIAcore system. We
      immobilized alpha-lactalbumin (LA) as a substrate protein on the sensor chip and
      the GroEL solution was passed over it. Whereas GroEL did not bind to the
      immobilized native LA, it associated with the immobilized Ca(2+)-depleted,
      disulfide bond-reduced form of LA (rLA) rapidly (kon = 1.96 x 10(5) M-1 S-1) and
      dissociated extremely slowly (koff = 2.08 x 10(-4) S-1), giving a low
      dissociation constant (KD = 1.06 nM). MgATP greatly accelerated the dissociation
      (koff = 0.15 +/- 0.02 S-1). The KD value remained almost unchanged when GroES
      and/or 10 microM ADP was included in the GroEL solution. However, when 1 mM ADP
      was included, the KD value of GroEL increased by 2 orders of magnitude solely due
      to the change in koff. When GroES and 1 mM ADP were included, no interaction with
      rLA was detected due to changes in both kon and koff. These results indicate that
      GroEL/ES has high and low affinity ADP binding sites and that occupation of the
      low affinity sites by ADP was responsible for the loss of ability to interact
      with the substrate protein. The effect of excess GroES on the preformed GroEL.rLA
      and GroEL/ES.rLA complexes was also examined. With increasing GroES, the
      dissociation of GroEL and GroEL/ES from rLA was accelerated, and thus the
      possibility is suggested that the substrate protein and GroES compete for the
      same site on GroEL.

PMID- 7650012
TI  - Identification of the functionally relevant calmodulin binding site in smooth
      muscle caldesmon.
AB  - The C-terminal region of smooth muscle caldesmon (CaD) interacts with calmodulin
      (CaM) and reverses CaD's inhibitory effect on the actomyosin ATPase activity. We
      have previously shown that the major CaM-binding site (site A) in this region is
      within the segment from Met-658 to Ser-666 (Zhan, Q., Wong, S. S., and Wang, C.
      L. A. (1991) J. Biol. Chem. 266, 21810-21814). Recently, another segment (site
      B), Asn-675 to Lys-695, was reported to bind CaM (Mezgueldi, M., Derancourt, J.,
      Calas, B., Kassab, R., and Fattoum, A. (1994) J. Biol. Chem. 269, 12824-12832).
      To assess the functional relevance of these two putative CaM-binding sites, we
      have examined three synthetic peptides regarding their effects on CaM's ability
      to reverse CaD-induced inhibition of actomyosin ATPase activity: GS17C (Gly-651
      to Ser-667), VG29C (Val-685 to Gly-713), each containing one CaM-binding site,
      and MG56C (Met-658 to Gly-713), which contains both sites. We found that although
      VG29C did bind CaM, its affinity was weakened by GS17C, and it failed to compete
      with CaD for CaM under the conditions where GS17C effectively displaced CaD from
      CaM. MG56C had an effect similar to that of GS17C. These experiments demonstrated
      that site A for CaM binding is involved in regulating the inhibitory property of
      CaD.

PMID- 7650013
TI  - G protein-coupled chemoattractant receptors regulate Lyn tyrosine kinase.Shc
      adapter protein signaling complexes.
AB  - Receptors for chemoattractants that direct the migration of phagocytic leukocytes
      to sites of injury/infection also modulate many other leukocyte functions that
      are critical to the inflammatory response. These chemoattractant receptors,
      members of the G protein-coupled heptahelical receptor family, have been
      classically linked to cell activation via phospholipase C, calcium, and protein
      kinase C. We show here that activation of the N-formyl peptide chemoattractant
      receptor stimulates an additional protein kinase C-independent pathway through
      the Src-related tyrosine kinase, Lyn, in human neutrophils. We demonstrate that
      activation of Lyn is associated with binding to the Shc adapter protein, which
      becomes phosphorylated on tyrosine residues. This interaction appears to be
      mediated via the Shc SH2 domain. Complexes of phosphorylated Lyn and Shc with
      phosphatidylinositol 3-kinase are rapidly formed in stimulated neutrophils,
      correlating with phosphatidylinositol 3,4,5-trisphosphate [corrected] formation
      and cell activation. This signaling pathway involving a Src-related kinase and
      the Shc adapter protein provides a potential mechanism linking chemoattractant
      receptors to downstream events involving Rac activation and NADPH oxidase.
      Regulation of Shc by G protein-coupled receptors may also allow these receptors
      to modulate the activity of the Ras/mitogen-activated protein kinase cascade.

PMID- 7650014
TI  - The sole lysine residue in porcine pepsin works as a key residue for catalysis
      and conformational flexibility.
AB  - Pepsin contains a single lysine residue which protrudes from the enzyme's
      surface, behind the active site cleft, on the C-terminal domain. Mutations of
      pepsin by site-directed mutagenesis of the Lys-319 residue were generated to
      study the structure-function relationships. Kinetic parameters, pH activity
      profiles, along with conformational analysis using circular dichroism (CD), and
      molecular modelling were examined for the wild-type (non-mutant) and mutant
      enzymes. The pepsin mutations, Lys-319-->Met and Lys-319-->Glu, resulted in a
      progressive increase in the Km and similar decrease in kcat, respectively, as
      well as being denatured at a lower pH than the wild-type pepsin. CD analysis
      indicated that mutations at Lys-319 resulted in changes in secondary structure
      fractions which were reflected in changes in enzymatic activity as compared to
      the wild-type pepsin, i.e. kinetic data and pH denaturation study. Molecular
      modelling of mutant enzymes indicated differences in flexibility in the flap loop
      region of the active site, the region around the entrance of the active site
      cleft, sub-site regions for peptide binding, and in the subdomains of the C
      terminal domain when compared to the wild-type enzyme. The results suggest that
      Lys-319, which is distal to the active site, is important to the
      flexibility/stability of the enzyme, as well as to its catalytic machinery.

PMID- 7650015
TI  - Characterization of an enhancer element in the human apolipoprotein C-III gene
      that regulates human apolipoprotein A-I gene expression in the intestinal
      epithelium.
AB  - Studies using transgenic mice indicate that expression of the human
      apolipoprotein (apo) A-I gene in the liver and small intestine is controlled by
      spatially distinct cis-acting DNA elements; hepatic expression is controlled by a
      domain defined by nucleotides -256 to -1, while small intestinal expression
      requires elements positioned 9 kilobases 3' to the gene, between nucleotides 
      1300 and -200 of the convergently transcribed apoC-III gene. In this report we
      have mapped this enhancer to a 260-base pair (bp) region of the apoC-III promoter
      spanning nucleotides -780 to -520. The elements contained within this 260-bp apoC
      III domain are sufficient to direct a pattern of expression in villus-associated
      enterocytes distributed along the duodenal-to-ileal axis that resembles that of
      mouse and human apoA-I. However, the elements produce inappropriate activation of
      apoA-I expression in proliferating and nonproliferating crypt epithelial cells,
      and in subpopulations of cholecystokinin- and serotonin-producing enteroendocrine
      cells. Cis-acting suppressors of these inappropriate patterns of expression are
      located outside of nucleotides -1300 to -200 of the human apoC-III gene. DNase I
      protection and gel mobility gel shift assays identified two 21-bp sequences,
      nucleotides -745 to -725 and -700 to -680 of human apoC-III, which bind nuclear
      proteins present in a human enterocyte-like cell line (Caco-2). These sequences
      are conserved in the orthologous mouse apoC-III gene. The 260-bp apoC-III element
      is the first intestinal enhancer that has been identified in an in vivo system
      and should provide insights about how cell lineage-specific, differentiation
      dependent, and cephalocaudal patterns of gene expression are established and
      maintained in the perpetually renewing gut epithelium. In addition, novel
      intestinal transcription factors may bind to the enhancer and regulate its
      activity.

PMID- 7650016
TI  - A role for acidic residues in di-leucine motif-based targeting to the endocytic
      pathway.
AB  - Recent reports have suggested that major histocompatibility complex class II
      molecules load peptide through a specialized compartment of the endocytic pathway
      and are targeted to this pathway by association with invariant chain (Iip31).
      Therefore we used a site-directed mutagenesis approach to determine whether Iip31
      possesses novel protein targeting signals. Our results indicate that two di
      leucine-like pairs mediate Iip31 targeting and that an acidic amino acid residue
      four or five residues N-terminal to each Iip31 di-leucine-like pair is required
      for endocytic targeting. Results from additional testing with hybrid Iip31
      molecules indicate that the acidic residues N-terminal to di-leucine pairs are
      critical for accumulation of these molecules in large endocytic vesicles and in
      some cases provide a structure favorable for internalization. The acidic residues
      N-terminal to di-leucine pairs are important in some sequence contexts in
      providing a structure favorable for internalization, whereas in other contexts an
      acidic residue is critical for targeting to, and formation of, large endocytic
      vesicles. Although our results do not support the idea that Iip31 possesses
      unique protein targeting motifs, they do suggest that di-leucine motifs may be
      recognized as part of a larger secondary structure. In addition, our data imply
      that the targeting motif requirements for internalization may differ from the
      requirements for further transport in the endocytic pathway.

PMID- 7650017
TI  - Androgen receptor antagonist versus agonist activities of the fungicide
      vinclozolin relative to hydroxyflutamide.
AB  - The mechanism of antiandrogenic activity of vinclozolin (3-(3,5-dichlorophenyl)-5
      methyl-5-vinyloxazolidine-2,4-dione), a dicarboximide fungicide under
      investigation for its potential adverse effects on human male reproduction, was
      investigated using recombinant human androgen receptor (AR). The two primary
      metabolites of vinclozolin in plants and mammals are M1 (2-[[3,5-dichlorophenyl)
      carbamoyl]oxy]-2-methyl-3-butenoic acid) and M2 (3',5'-dichloro-2-hydroxy-2
      methylbut-3-enanilide). Both metabolites, in a dose-dependent manner, target AR
      to the nucleus and inhibit androgen-induced transactivation mediated by the mouse
      mammary tumor virus promoter. M2 is a 50-fold more potent inhibitor than M1 and
      only 2-fold less than hydroxyflutamide. In the presence of dihydrotestosterone
      (50 nM), M2 (0.2-10 microM) inhibits androgen-induced AR binding to androgen
      response element DNA. In the absence of dihydrotestosterone, concentrations of 10
      microM M2 or hydroxyflutamide promote AR binding to androgen response element DNA
      and activation of transcription. Agonist activities of M2 and hydroxyflutamide
      occur at 10-fold lower concentrations with the mutant AR (Thr877 to Ala)
      endogenous to LNCaP human prostate cancer cells. The results indicate that
      androgen antagonists can act as agonists, depending on ligand binding affinity,
      concentration, and the presence of competing natural ligands.

PMID- 7650018
TI  - Parathyroid hormone and parathyroid hormone-related peptide inhibit the apical
      Na+/H+ exchanger NHE-3 isoform in renal cells (OK) via a dual signaling cascade
      involving protein kinase A and C.
AB  - Parathyroid hormone (PTH) and parathyroid hormone-related peptide (PTHRP)
      interact with a common G protein-coupled receptor and stimulate production of
      diverse second messengers (i.e. cAMP, diacylglycerol, and inositol 1,4,5
      trisphosphate) that varies depending on the target cell. In renal proximal tubule
      OK cells, PTH inhibits the activity of the apical membrane Na+/H+ exchanger,
      although it is unclear whether the signal is transmitted through protein kinase A
      (PKA) and/or protein kinase C (PKC). To delineate the signaling circuitry, a
      series of synthetic PTH and PTHRP fragments were used that stimulate the
      adenylate cyclase-cAMP-PKA and/or phospholipase C-diacylglycerol-PKC pathways.
      Human PTH-(1-34) and PTHRP-(1-34) stimulated adenylate cyclase and PKC activity,
      whereas the PTH analogues, PTH-(3-34), PTH-(28-42), and PTH-(28-48), selectively
      enhanced only PKC activity. However, each peptide fragment inhibited Na+/H+
      exchanger activity by 40-50%, suggesting that PKC and possibly PKA were capable
      of transducing the PTH/PTHRP signal to the transporter. This was corroborated
      when forskolin and phorbol 12-myristate 13-acetate (PMA), direct agonists of
      adenylate cyclase and PKC, respectively, both inhibited the Na+/H+ exchanger. The
      specific PKA antagonist, H-89, abolished the forskolin-mediated suppression of
      Na+/H+ exchanger activity, but did not prevent the inhibitory effects of PTH-(1
      34) or PMA. In comparison, the potent PKC inhibitor, chelerythrine chloride,
      prevented the inhibition of Na+/H+ exchanger activity mediated by PTH-(28-48) and
      PMA but did not avert the negative regulation caused by PTH-(1-34) or forskolin.
      However, inhibition of both PKA and PKC prevented PTH-(1-34)-mediated suppression
      of Na+/H+ exchanger activity, indicating that PTH-(1-34) acted through both
      signaling pathways. In addition, Northern blot analysis revealed the presence of
      only the NHE-3 isoform of the Na+/H+ exchanger in OK cells. In summary, these
      results demonstrated that NHE-3 is expressed in OK cells and that activation of
      the PTH receptor can stimulate both the PKA and PKC pathways, each of which can
      independently lead to inhibition of NHE-3 activity.

PMID- 7650019
TI  - The groove between the alpha- and beta-subunits of hormones with lutropin (LH)
      activity appears to contact the LH receptor, and its conformation is changed
      during hormone binding.
AB  - Gonadotropins are heterodimeric glycoprotein hormones that control vertebrate
      fertility through their actions on gonadal lutropin (luteinizing hormone, LH) and
      follitropin (follicle-stimulating hormone, FSH) receptors. The beta-subunits of
      these hormones control receptor binding specificity; however, the region of the
      beta-subunit that contacts the receptor has not been identified. By a process of
      elimination we show this contact to be the portions of beta-subunit loops one and
      three found in a hormone groove created by the juxtaposition of the alpha- and
      beta-subunits. Most other regions of the beta-subunit can be recognized by
      antibodies that bind to human chorionic hormone (hCG)-receptor complexes or
      replaced without disrupting hormone function. Using a series of bovine LH/hCG and
      human FSH/hCG beta-subunit chimeras we identified key hCG beta-subunit residues
      in the epitopes of two antibodies that bind to hCG-receptor complexes. These
      epitopes include the surfaces of beta-subunit loops one and three near residue 74
      on the outside of the hormone groove and parts of the C-terminal end of the "seat
      belt" that holds the two subunits together. The antibody that recognized residue
      74 bound to receptor complexes containing most mammalian lutropins better than to
      the free hormones, an indication that the outside surface of the beta-subunit
      groove is altered during hormone binding. This region of the beta-subunit is
      furthest from the alpha-subunit and is recognized equally well in the free beta
      subunit and in the heterodimer. Thus, the receptor associated increase in
      antibody binding appears due to an interaction of this portion of the beta
      subunit with the receptor and not to an effect of the receptor on the relative
      positions of the alpha- and beta-subunits. Unlike most previous studies designed
      to identify portions of the beta-subunit likely to contact the LH receptor, this
      indirect approach provides data that are more easily interpreted because it does
      not rely on the use of mutations that disrupt hormone function. The approach
      described here should be valuable for studying the receptor interactions of other
      complex ligands.

PMID- 7650020
TI  - Model of human chorionic gonadotropin and lutropin receptor interaction that
      explains signal transduction of the glycoprotein hormones.
AB  - The goal of these studies was to devise a model that explains how human chorionic
      gonadotropin (hCG) interacts with lutropin (LH) receptors to elicit a hormone
      signal. Here we show that alpha-subunit residues near the N terminus, the exposed
      surface of the cysteine knot, and portions of the first and third loops most
      distant from the beta-subunit interface were recognized by antibodies that bound
      to hCG-receptor complexes. These observations were combined with similar data
      obtained for the beta-subunit (Cosowsky, L., Rao, S.N.V., Macdonald, G.J.,
      Papkoff, H., Campbell, R.K., and Moyle, W.R. (1995) J. Biol. Chem. 270, 20011
      20019), information on residues of hCG that can be changed without disrupting
      hormone function, the crystal structure of deglycosylated hCG, and the crystal
      structure of a leucine-repeat protein to devise a model of hCG-receptor
      interaction. This model suggest that the extracellular domain of the LH receptor
      is "U-" or "J"-shaped and makes several contacts with the transmembrane domain.
      High affinity hormone binding results from interactions between residues in the
      curved portion of the extracellular domain of the receptor and the groove in the
      hormone formed by the apposition of the second alpha-subunit loop and the first
      and third beta-subunit loops. Most of the remainder of the hormone is found in
      the large space between the arms of the extracellular domain and makes few, if
      any, additional specific contacts with the receptor needed for high affinity
      binding. Signal transduction is caused by steric or other influences of the
      hormone on the distance between the arms of the extracellular domain, an effect
      augmented by the oligosaccharides. Because the extracellular domain is coupled at
      multiple sites to the transmembrane domain, the change in conformation of the
      extracellular domain is relayed to the transmembrane domain and subsequently to
      the cytoplasmic surface of the plasma membrane. While the model does not require
      the hormone to contact the transmembrane domain to initiate signal transduction,
      small portions of both subunits may be near the transmembrane domain and assist
      in initiating the hormonal signal. This is the first model that is consistent
      with all known information on the activity of the gonadotropins including the
      amounts of the hormone that are exposed in the hormone-receptor complex, the
      apparent lack of specific contacts between much of the hormone and the receptor,
      and the roles of the oligosaccharides in signal transduction.(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 7650021
TI  - Structure of the rat V1a vasopressin receptor gene and characterization of its
      promoter region and complete cDNA sequence of the 3'-end.
AB  - The gene encoding the rat V1a arginine vasopressin (AVP) receptor was isolated,
      and its structural organization and 5'-flanking region were characterized. In
      addition, the complete cDNA sequence of the major transcript of the rat V1a
      receptor gene was determined. Southern blots demonstrated a single copy of the
      V1a receptor gene in the rat genome, spanning a region of 3.8 kilobases (kb) and
      consisting of two exons and one intron (1.8 kb). The location of the intron was
      unique among G protein-coupled receptor genes in that the first exon encodes six
      of the seven transmembrane regions, the seventh region being encoded by the
      second exon. Primer extension, RNase protection, and rapid amplification of the
      5'-end of the cDNA identified three transcriptional initiation sites (-405, -243,
      and -237), the major transcription initiation sites being mapped to positions 
      243 and -237 base pairs (bp) upstream of the ATG initiation codon (+1 bp). This
      portion of the 5'-flanking region has neither a TATA nor a CCAAT box, is GC-rich
      but has no GC box motif, and has features of promoters seen in housekeeping
      genes. Chimeras containing 2.2 kb of the 5'-flanking region and deletion analyses
      using the chloramphenicol acetyltransferase gene indicated that a "minimal"
      region, exhibiting promoter activity and tissue specificity, is located between
      nucleotides -296 and -221, when transfected into vascular smooth muscle cells.
      Gel mobility shift assay and Southwestern blotting suggested that approximately
      30- and approximately 28-kDa nuclear proteins specifically bind to this region.
      Rapid amplification of the 3'-end of the cDNA showed that the major transcript
      terminates 442 bp downstream of the stop codon, in agreement with the mRNA size
      (2.1 kb). This study demonstrated a distinctive feature in the structural
      organization of the AVP-oxytocin receptor family genes, and characterization of
      the 5'-flanking region reported here will lead to a better understanding of the
      mechanism of transcriptional regulation of the rat V1a AVP receptor gene.

PMID- 7650022
TI  - Feasibility of a mitochondrial pyruvate malate shuttle in pancreatic islets.
      Further implication of cytosolic NADPH in insulin secretion.
AB  - Previous studies indicated that in pancreatic islets the amount of glucose
      derived pyruvate that enters mitochondrial metabolism via carboxylation is
      approximately equal to that entering via decarboxylation and that both
      carboxylation and decarboxylation are correlated with capacitation of glucose
      metabolism and insulin release. The relatively high rate of carboxylation is
      consistent with the current study's finding that pyruvate carboxylase is as
      abundant in pancreatic islets as it is in liver and kidney. Since islets do not
      contain phosphoenolpyruvate carboxykinase and, therefore, cannot carry out
      glyconeogenesis from pyruvate, the carboxylase might be present in the islet to
      participate in novel anaplerotic reactions. This idea was first explored by
      incubating mitochondria from various tissues with pyruvate. Mitochondria from
      tissues, such as pancreatic islets, liver, and kidney, in which pyruvate
      carboxylase is abundant, exported a large amount of malate and little or no
      citrate, isocitrate, and aspartate to the medium. The amount of malate within the
      mitochondria was < 1% that in the medium. When pancreatic islet mitochondria were
      incubated with [1-14C]pyruvate, radioactive carbon appeared in the medium
      primarily in malate. Very little radioactivity appeared in amino acids, and
      little or no radioactivity appeared in citrate and isocitrate. Carbon 1 of
      pyruvate can be incorporated into malate and other citric acid cycle
      intermediates only via carboxylation, as this carbon would be lost via
      decarboxylation when pyruvate enters the citric acid cycle as acetyl-CoA via the
      pyruvate dehydrogenase reaction. The amount of malate formed equaled the 14CO2
      formed and the radioactivity from C-1 of pyruvate recovered in malate slightly
      exceeded the formation of 14CO2 in agreement with our previous studies that
      reported a high rate of carboxylation of pyruvate in intact islets. When intact
      pancreatic islets were incubated with methyl [U-14C]succinate as a mitochondrial
      source of four-carbon dicarboxylic acids, radioactivity appeared in pyruvate and
      lactate. Taken together with previous studies, the current results suggest that
      during glucose-induced insulin secretion there is a shuttle operating across the
      mitochondrial membrane in which glucose-derived pyruvate is taken up by
      mitochondria and carboxylated to oxaloacetate by pyruvate carboxylase. The
      oxaloacetate is converted to malate which exits the mitochondrion, where, in the
      cytosol, it is decarboxylated to pyruvate in the reaction catalyzed by malic
      enzyme. This pyruvate re-enters mitochondrial pools. Such a cycle produces NADPH
      in the cytosol. Since it is a cycle, this shuttle can produce far more NADPH than
      the pentose phosphate pathway, which is known to be a very minor route of glucose
      metabolism in the islet.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7650023
TI  - The in vitro translocase activity of lambda terminase and its subunits. Kinetic
      and biochemical analysis.
AB  - The terminase holoenzyme of bacteriophage lambda is a multifunctional protein
      composed of two subunits, gpNu1 and gpA. In vitro, under certain conditions,
      terminase can render DNAs from various sources, of varying lengths and termini,
      resistant to degradation by high concentrations of DNase I. This reaction is
      completely dependent on the presence of terminase, proheads, a hydrolyzable
      triphosphate, and a divalent metal ion, and we propose that it is the result of
      translocation of DNA into proheads by terminase. This reaction is stoichiometric
      with respect to terminase, DNA, and proheads and can be supported by all
      deoxyribo- and ribonucleoside triphosphates, but not by the corresponding
      diphosphates or nonhydrolyzable ATP analogs. Mg2+ and Ca2+ promote the reaction,
      but Mn2+ and Zn2+ do not. In the absence of spermidine, translocase activity is
      low, but addition of the Escherichia coli protein integration host factor (IHF)
      promotes specific translocation of only those DNA fragments containing the
      terminase-binding site, cosB. When spermidine is present, nonspecific
      translocation of DNA from any source is stimulated. Under these conditions IHF no
      longer promotes specificity, but translocation of only cosB-containing DNA
      fragments can be restored by addition of small amounts of a dialyzed and RNase
      treated E. coli extract, suggesting that additional host factor(s) may be
      involved in determination of packaging specificity. To a limited extent, gpA
      alone can promote translocation, but gpNu1, which has no translocase activity on
      its own, must be added to approach the holoenzyme-like activity levels. Formation
      of viable phage cannot be accomplished by gpA in the absence of gpNu1.

PMID- 7650024
TI  - G12 requirement for thrombin-stimulated gene expression and DNA synthesis in
      1321N1 astrocytoma cells.
AB  - Thrombin stimulation of 1321N1 astrocytoma cells leads to Ras-dependent AP-1
      mediated transcriptional activation and to DNA replication. In contrast to what
      has been observed in most cell systems, in 1321N1 cells these responses are
      pertussis toxin-insensitive. The pertussis toxin-insensitive G-protein G12 has
      been implicated in cell growth and transformation in different cell systems. We
      have examined the potential role of this protein in AP-1-mediated transcriptional
      activation and DNA synthesis in 1321N1 cells. Transient expression of an
      activated (GTPase-deficient) mutant of G alpha 12 increased AP-1-dependent gene
      expression. This response was inhibited by co-expression of a dominant negative
      Ala-15 Ras protein. To determine whether the pertussis toxin-insensitive G12
      protein is involved in the thrombin-stimulated DNA synthesis, an inhibitory
      antibody against the C-terminal sequence of G alpha 12 subunit was microinjected
      into 1321N1 cells. Microinjection of the anti-G alpha 12 resulted in a
      concentration-dependent inhibition of thrombin-stimulated DNA synthesis. In
      contrast, microinjection of nonimmune IgG or an antibody directed against the C
      terminus of G alpha o did not reduce the mitogenic response to thrombin.
      Furthermore, microinjection of the anti-G alpha 12 antibody had no effect on
      fibroblast growth factor-stimulated DNA synthesis. These results demonstrate a
      specific role for G alpha 12 in the mitogenic response to thrombin in human
      astroglial cells.

PMID- 7650026
TI  - Yeast viral 20 S RNA is associated with its cognate RNA-dependent RNA polymerase.
AB  - Most Saccharomyces cerevisiae strains carry in their cytoplasm 20 S RNA, a linear
      single-stranded RNA molecule of 2.5 kilobases in size. 20 S RNA copy number is
      greatly induced in stress conditions such as starvation, with up to 100,000
      copies per cell. 20 S RNA has coding capacity for a protein of 91 kDa (p91) with
      sequences diagnostic of RNA-dependent RNA polymerases of (+) strand and double
      stranded RNA viruses. We detected p91 in 20 S RNA-carrying strains with specific
      antisera. The amount of p91 in growing cells is higher than that of stationary
      cells and similar to the one in 20 S RNA-induced cells. Although 20 S RNA is not
      encapsidated into viral particles, p91 non-covalently forms a ribonucleoprotein
      complex with 20 S RNA. This suggests a role of p91 in the RNA to RNA synthesis
      processes required for 20 S RNA replication. Although the strain analyzed also
      harbors 23 S RNA, a closely related single-stranded RNA, 23 S RNA is not
      associated with p91 but with its putative RNA polymerase, p104. Similarly, 20 S
      RNA is not associated with p104 but with p91. These results suggest that 20 S RNA
      and 23 S RNA replicate independently using their respective cognate RNA
      polymerases.

PMID- 7650025
TI  - Ricin cytotoxicity is sensitive to recycling between the endoplasmic reticulum
      and the Golgi complex.
AB  - Cytotoxic proteins that kill mammalian cells by catalytically inhibiting protein
      synthesis must enter the cytosol in order to reach their substrates. With the
      exception of diphtheria toxin, which enters the cytosol from acidified endosomes,
      the intracellular site of translocation of other toxins including ricin,
      Escherichia coli Shiga-like toxin-1, and Pseudomonas exotoxin A is likely to
      involve early compartments of the secretory pathway. We have used a molecular
      approach to identify the site and mechanism of toxin delivery to the cytosol by
      transiently expressing mutant GTPases that inhibit the assembly of biochemical
      complexes mediating anterograde and retrograde transport in the exocytic and
      endocytic pathways. The results provide evidence to suggest that receptors
      actively recycling between the endoplasmic reticulum and terminal Golgi
      compartments are essential for toxin translocation to the cytosol from the
      endoplasmic reticulum. The rapid kinetics of intoxication demonstrate a
      substantial level of bidirectional membrane flow and sorting through the early
      secretory pathway.

PMID- 7650027
TI  - Comparison of the reactivity of tetradecenoic acids, a triacsin, and unsaturated
      oximes with four purified Saccharomyces cerevisiae fatty acid activation
      proteins.
AB  - Saccharomyces cerevisiae contains at least five acyl-CoA synthetases (fatty acid
      activation proteins, or Faaps). Four FAA genes have been recovered to date.
      Recent genetic studies indicate that Faa1p and Faa4p are involved in the
      activation of imported fatty acids, while Faa2p activates endogenous pools of
      fatty acids. We have now purified Faa4p from S. cerevisiae and compared its fatty
      acid substrate specificity in vitro with the specificities of purified Faa1p,
      Faa2p, and Faa3p. Among C8-C18 saturated fatty acids, Faa4p and Faa1p both prefer
      C14:0. Surveys of C14 fatty acids with single cis-double bonds at C2-C12
      indicated that Faa4p and Faa1p prefer Z9-tetradecenoic acid, although Faa4p's
      preference is much greater and also evident in C16 and C18 fatty acids. Faa4p's
      selectivity for fatty acids with a C9-C10 cis-double bond is a feature it shares
      with Faa3p and is notable since in yeast Ole1p, a microsomal cis-delta 9
      desaturase, accounts for de novo production of monoenoic acyl-CoAs from saturated
      acyl-CoA substrates. Faa4p has no detectable acyl-CoA synthetase activity when
      incubated with tetradecenoic acids having a trans-double bond at C2-3, C4-5, C5
      6, C6-7, C7-8, or C9-10. Faa3p can only use E9-tetradecenoic acid as a substrate,
      while E4-, E6- and E9-tetradecenoic acids can be used by Faa1p and Faa2p. E2
      tetradecenoic acid is an Faap inhibitor, with Faa2p exhibiting the greatest
      sensitivity (IC50 = 2.6 +/- 0.2 microM). Triacsin C (1-hydroxy-3-(E,E,E,2',4',7'-
      undecatrienylidine)-1,2,3-triazene) has trans-double bonds at positions that
      correspond to those in E2-, E5-, and E7-tetradecenoic acids. This compound is a
      potent inhibitor of Faa2p (Ki = 15 +/- 1 nM; competitive with fatty acid), less
      potent against Faa4p (Ki = 2 microM), and not active against Faa1p or Faa3p (IC50
      > 500 microM). Analysis of an n-tetradecanal plus a series of oximes (tridecanal
      oxime, 1-azadeca-1,3,5-trienol, and 1-azaundeca-1,3,5-trienol) indicated that the
      combination of an azenol moiety (R-CH = N-OH) plus adjacent unsaturation are
      critical for triacsin C's selective inhibition of Faa2p. Triacsin C and oxime
      derivatives appear to be very useful for defining differences in molecular
      recognition among S. cerevisiae acyl-CoA synthetases. The > 25,000-fold range in
      the inhibitory effects of triacsin C on these four Faaps suggests that it may be
      possible to develop other selective inhibitors of eukaryotic acyl-CoA
      synthetases.

PMID- 7650029
TI  - SecYEG and SecA are the stoichiometric components of preprotein translocase.
AB  - The transport of large preproteins across the Escherichia coli plasma membrane is
      catalyzed by preprotein translocase, comprised of the peripherally bound SecA
      subunit and an integrally bound heterotrimeric domain consisting of the SecY,
      SecE, and SecG subunits. We have now placed the secY, secE, and secG genes under
      the control of an arabinose-inducible promoter on a multicopy plasmid. Upon
      induction, all three of the proteins are strongly overexpressed and recovered in
      the plasma membrane fraction. These membranes show a strong enhancement of 1)
      translocation ATPase activity, 2) preprotein translocation, 3) capacity for SecA
      binding, and 4) formation of the membrane-inserted form of SecA. These data
      establish that SecY, SecE, and SecG constitute the integral membrane domain of
      preprotein translocase.

PMID- 7650028
TI  - Increased phosphorylation of histone H1 in mouse fibroblasts transformed with
      oncogenes or constitutively active mitogen-activated protein kinase kinase.
AB  - We compared the nucleosomal organization, histone H1 subtypes, and histone H1
      phosphorylated isoforms of ras-transformed and parental 10T1/2 mouse fibroblasts.
      In agreement with previous studies, we found that ras-transformed mouse
      fibroblasts have a less condensed chromatin structure than normal fibroblasts.
      ras-transformed and parental 10T1/2 cells had similar amounts of H1 subtypes,
      proteins that have a key role in the compaction of chromatin. However, labeling
      studies with 32P and Western blot experiments with an antiphosphorylated H1
      antibody show that interphase ras-transformed cells have higher levels of
      phosphorylated H1 isoforms than parental cells. G1/S phase-arrested ras
      transformed cells had higher amounts of phosphorylated H1 than G1/S phase
      arrested parental cells. Mouse fibroblasts transformed with fes, mos, raf, myc,
      or constitutively active mitogen-activated protein (MAP) kinase kinase had
      increased levels of phosphorylated H1. These observations suggest that increased
      phosphorylation of H1 is one of the consequences of the persistent activation of
      the mitogen-activated protein kinase signal transduction pathway. Indirect
      immunofluorescent studies show that phosphorylated H1b is localized in centers of
      RNA splicing in the nucleus, suggesting that this modified H1 subtype is
      complexed to transcriptionally active chromatin.

PMID- 7650030
TI  - Expression of human chromosome 19p alpha(1,3)-fucosyltransferase genes in normal
      tissues. Alternative splicing, polyadenylation, and isoforms.
AB  - The human alpha(1,3)-fucosyltransferase genes FUT3, FUT5, and FUT6 form a cluster
      on chromosome 19p13.3. Expression was studied using reverse transcriptase
      polymerase chain reaction, rapid amplification of cDNA ends, and Northern
      analyses. FUT3 and FUT6 were expressed at high levels, while FUT5 expression was
      lower and restricted to fewer cell types. Alternatively spliced transcripts were
      identified for FUT3 and FUT6 in kidney, liver, and colon. A 2.37-kilobase pair
      (kb) FUT3 transcript, detected at high levels in kidney and colon, was absent in
      liver. FUT6 expression was characterized by a 3.5-kb transcript present in kidney
      and liver, and a 2.5-kb transcript in colon and liver. Two polyadenylation sites
      were shown for FUT5, but absence of consensus sequences suggests reduced
      efficiency for cleavage and polyadenylation. Two polyadenylation sites were also
      shown for FUT6, with the alternatively spliced downstream signal in tissues
      expressing high levels of FUT6. In these tissues, additional splicing results in
      isoforms with catalytic domain deletions. No detectable alpha(1,3)- or alpha(1,4)
      fucosyltransferase activity was found in assays of cells transfected with FUT6
      isoform cDNAs. Thus, tissue-specific post-transcriptional modifications are
      associated with expression patterns of FUT3, FUT5, and FUT6.

PMID- 7650031
TI  - Do transmembrane segments in proteolyzed sarcoplasmic reticulum Ca(2+)-ATPase
      retain their functional Ca2+ binding properties after removal of cytoplasmic
      fragments by proteinase K?
AB  - The present study was undertaken to investigate the Ca2+ binding properties of
      sarcoplasmic reticulum Ca(2+)-ATPase after removal of the cytoplasmic regions by
      treatment with proteinase K. One of the proteolysis cleavage sites (at the end of
      M6) was found unexpectedly close to the predicted membrane-water interphase, but
      otherwise the cleavage pattern was consistent with the presence of 10
      transmembrane ATPase segments. C-terminal membranous peptides containing the
      putative transmembrane segments M7 to M10 accumulated after prolonged
      proteolysis, as well as large water-soluble fragments containing most of the
      phosphorylation and ATP-binding domain. Ca2+ binding was intact after cleavage of
      the polypeptide chain in the N-terminal region, but cuts at other locations
      disrupted the high affinity binding and sequential dissociation properties
      characteristic of native sarcoplasmic reticulum, leaving the translocation sites
      with only weak affinity for Ca2+. High affinity Ca2+ binding could only be
      maintained when proteolysis and subsequent manipulations took place in the
      presence of a Ca2+ concentration high enough to ensure permanent occupation of
      the binding sites with Ca2+. We conclude that in the absence of Ca2+, the complex
      of membrane-spanning segments in proteolyzed Ca(2+)-ATPase is labile, probably
      because of relatively free movement or rearrangement of individual segments. Our
      study, which is discussed in relation to results obtained on Na+,K(+)-ATPase and
      H+,K(+)-ATPase, emphasizes the importance of the cytosolic segments of the main
      polypeptide chain in exerting constraints on the intramembranous domain of a P
      type ATPase.

PMID- 7650032
TI  - An epidermal growth factor receptor-leukocyte tyrosine kinase chimeric receptor
      generates ligand-dependent growth signals through the Ras signaling pathway.
AB  - Leukocyte tyrosine kinase (LTK) is a receptor tyrosine kinase that belongs to the
      insulin receptor family. LTK is mainly expressed in pre B cells and brain.
      Previously we cloned the full-length cDNA of human LTK, but no ligands have so
      far been identified, and hence, very little is known about the physiological role
      of LTK. To analyze the function of the LTK kinase, we constructed chimeric
      receptors composed of the extracellular domain of epidermal growth factor
      receptor and the transmembrane and the cytoplasmic domains of LTK and established
      cell lines that stably express these chimeric molecules. When cultured in medium
      containing EGF, growth of these cell lines was stimulated, and these fusion
      proteins became autophosphorylated and associated with Shc in vivo in a ligand
      dependent manner. By treatment with EGF, Shc was associated with the Grb2/Ash-Sos
      complex. Our analyses demonstrate that LTK associates with Grb2/Ash through an
      internal adaptor, Shc, depending on a ligand stimulation. The LTK binding site
      for Shc was tyrosine 862 at the carboxyl-terminal domain and to a lesser extent
      tyrosine 485 at the juxtamembrane domain. Both of them are located in NP/AXY
      motif which is consistent with binding sites for Shc. These findings demonstrate
      that LTK can activate the Ras pathway in a ligand-dependent manner and that at
      least one of the functions of this kinase is involved in the cell growth.

PMID- 7650033
TI  - The presence of beta-D-ribosyl-1-monophosphodecaprenol in mycobacteria.
AB  - Biosynthesis of the cell envelope in mycobacteria is largely unknown; however,
      several antituberculosis drugs apparently interfere with this process. Recently,
      we described a lipid intermediate for the biosynthesis of the cell wall
      arabinogalactan/arabinomannan of Mycobacterium smegmatis: beta-D-arabinofuranosyl
      1-monophosphodecaprenol (Wolucka, B. A., McNeil, M. R., de Hoffmann, E.,
      Chojnacki, T., and Brennan, P. J. (1994) J. Biol. Chem. 269, 23328-23335). In the
      present work, by means of gas chromatography-mass spectrometry, fast atom
      bombardment tandem mass spectrometry, and proton NMR, the major pentose
      containing component of the polyprenyl-P-sugar family from M. smegmatis was
      characterized as beta-D-ribosyl-1-monophosphodecaprenol (decaprenyl-P-ribose).
      Additionally, the structure of a minor arabinose-containing compound, beta-D
      arabinosyl-1-monophosphooctahydroheptaprenol, could be deduced. In vivo labeling
      experiments with [14C]glucose demonstrated unequivocally that decaprenyl-P-ribose
      is actively synthesized in Mycobacterium tuberculosis H37Ra and Mycobacterium
      avium serovar 4. It is proposed that decaprenyl-P-ribose could be a precursor for
      the biosynthesis of either some unknown ribose-containing cell envelope polymers
      of mycobacteria or the arabinan part of the cell wall
      arabinogalactan/arabinomannan due to the presence of a 2'-epimerase activity at
      some late stages of the arabinogalactan/arabinomannan biosynthesis.

PMID- 7650034
TI  - Functional interactions between retinoic acid receptor-related orphan nuclear
      receptor (ROR alpha) and the retinoic acid receptors in the regulation of the
      gamma F-crystallin promoter.
AB  - We have previously demonstrated that an everted repeat of the hexamer PuGGTCA
      located within the gamma F-crystallin promoter mediates activation of the murine
      gamma F-crystallin gene by retinoic acid and thyroid hormone receptors. Here, we
      show that the recently identified retinoic acid receptor-related orphan nuclear
      receptor (ROR alpha) is expressed in the murine lens and activates the gamma F
      crystallin promoter. In contrast to the retinoic acid and thyroid hormone
      receptors, activation of the gamma F-crystallin promoter by ROR alpha requires
      binding to the single 3' half-site and spacer sequences of gamma F-crystallin
      hormone response element (gamma F-HRE). We further demonstrate that ROR alpha
      dependent activation is repressed by the competitive binding of retinoic acid
      receptor/retinoid X receptor heterodimers to the gamma F-HRE in the absence of
      all-trans-retinoic acid. These studies suggest that the interplay of retinoid
      receptors and ROR alpha on the gamma F-HRE may constitute an important mechanism
      regulating gamma F-crystallin gene expression in the murine lens.

PMID- 7650035
TI  - Substrate specificity, gene structure, and tissue-specific distribution of
      multiple human 3 alpha-hydroxysteroid dehydrogenases.
AB  - We have expressed in Escherichia coli functionally active proteins encoded by two
      human cDNAs that were isolated previously by using rat 3 alpha-hydroxysteroid
      dehydrogenase cDNA as the probe. The expressed proteins catalyzed the
      interconversion between 5 alpha-dihydrotestosterone and 5 alpha-androstane-3
      alpha,17 beta-diol. Therefore, we name these two enzymes type I and type II 3
      alpha-hydroxysteroid dehydrogenases. The type I enzyme has a high affinity for
      dihydrotestosterone, whereas the type II enzyme has a low affinity for the
      substrate. The tissue-specific distribution of these two enzymes was determined
      by reverse transcription polymerase chain reaction using gene-specific
      oligonucleotide primers. The mRNA transcript of the type I enzyme was found only
      in the liver, whereas that of the type II enzyme appeared in the brain, kidney,
      liver, lung, placenta, and testis. The structure and sequence of the genes
      encoding these two 3 alpha-hydroxysteroid dehydrogenases were determined by
      analysis of genomic clones that were isolated from a lambda EMBL3 SP6/T7 library.
      The genes coding for the type I and type II enzymes were found to span
      approximately 20 and 16 kilobase pairs, respectively, and to consist of 9 exons
      of the same sizes and boundaries. The exons range in size from 77 to 223 base
      pairs (bp), whereas the introns range in size from 375 bp to approximately 6
      kilobase pairs. The type I gene contains a TATA box that is located 27 bp
      upstream of multiple transcription start sites. In contrast, the type II gene
      contains two tandem AP2 sequences juxtaposed to a single transcription start
      site.

PMID- 7650037
TI  - Hydroxyarginine-containing polyphenolic proteins in the adhesive plaques of the
      marine mussel Mytilus edulis.
AB  - An unusual polymorphic protein family of nine or more variants has been isolated
      from the byssal adhesive plaques and foot of the marine mussel Mytilus edulis. In
      accordance with established terminology, the family is referred to as M. edulis
      foot protein 3 or simply Mefp-3. Variants of Mefp-3 have molecular masses of
      about 6 kDa, isoelectric points greater than 10.5, and an amino acid composition
      dominated by six amino acids: glycine, asparagine, 3,4-dihydroxyphenylalanine
      (Dopa), tryptophan, arginine, and an unknown basic amino acid. The latter has
      been isolated and identified as 4-hydroxyarginine using fast atom bombardment
      mass spectrometry and appropriate standards. The primary structure of variant
      Mefp-3F has been determined by peptide mapping using automated Edman sequencing
      in combination with fast atom bombardment and matrix-assisted laser desorption
      ionization mass spectrometry: ADYYGPNYGPPRRYGGGNYNRYNRYGRRYGGYKGWNNGWNRGRRGKYW
      where Y represents Dopa, and R represents hydroxyarginine. Notably, the 4
      occurrences of RY are marked by a resistance to trypsin digestion. Although the
      conversion of tyrosines to Dopa is essentially complete, hydroxylation of
      arginines varies between 40 and 80%. In contrast to other mussel adhesive
      proteins such as Mefp-1 and -2 which have large numbers of highly conserved,
      tandemly repeated peptide motifs, Mefp-3 has only short sporadic repeats. The
      specific function of Mefp-3 in byssal adhesion is unknown.

PMID- 7650036
TI  - Enhanced folding and processing of a disulfide mutant of the human
      asialoglycoprotein receptor H2b subunit.
AB  - Unfolded forms of the H2b subunit of the human asialoglycoprotein receptor, a
      galactose-specific C-type lectin, are degraded in the endoplasmic reticulum (ER),
      whereas folded forms of the protein can mature to the cell surface (Wikstrom, L.,
      and Lodish, H. F. (1993) J. Biol. Chem. 268, 14412-14416). There are eight
      cysteines in the exoplasmic domain of the protein, forming four disulfide bonds
      in the folded protein. We have constructed double cysteine to alanine mutants for
      each of the four disulfide bonds and examined the folding and metabolic fate of
      each of the mutants in transfected 3T3 fibroblasts. We find that mutation of the
      two cysteines nearest to the transmembrane region (C1) does not prevent proper
      folding of the protein, whereas mutations of the other three disulfides prevent
      proper folding of the protein and all of the mutant proteins are degraded in the
      ER. A normal (approximately 20%) fraction of the C1 mutant protein exists the
      endoplasmic reticulum and is processed in the Golgi complex, and it does so at a
      faster rate compared to the wild-type. Furthermore, the folded form of this
      mutant protein is more resistant to unfolding by dithiothreitol than the wild
      type. The C1 mutant protein is expressed on the cell surface and can form a
      functional receptor with the H1 subunit with similar binding affinities for
      natural ligands as that of the wild-type receptor. The same fraction of newly
      made mutant and wild-type proteins (approximately 80%) remain in the ER, but the
      mutant protein is degraded more quickly. Thus, the presence of the C1 disulfide
      bond in the wild-type receptor both reduces the rate of protein folding and exit
      to the Golgi and slows the rate of ER degradation of the portion (approximately
      80%) of the receptor that never folds properly.

PMID- 7650038
TI  - In vivo characterization of phytochrome-phycocyanobilin adducts in yeast.
AB  - The in vivo reconstitution of phycocyanobilin with apophytochrome leads to
      photoreversible adducts in living yeast cells. Investigations with the rice
      phytochrome A phycocyanobilin adduct (PHYA*) and the tobacco phytochrome B
      phycocyanobilin adduct (PHYB*) show that the protein stability in yeast is
      independent of the form of the photoreceptor. After in vivo assembly and
      irradiation with red light, 25.6% of the far-red light-absorbing form of PHYB*
      exhibited dark reversion with a half-life time of approximately 20 min. Control
      experiments with PHYA* revealed no dark reversion. The data indicate that the
      molecular basis for this reaction is the formation of heterodimers between the
      red and the far-red light absorbing form of phytochrome. Electron microscopic in
      situ localizations and in vitro sequestering experiments showed that phytochrome
      A was able to sequester in yeast. On the electron microscopic level, the
      sequestered areas of phytochrome from etiolated plants and yeast are
      indistinguishable. The sequestering reaction in yeast is independent of the
      formation of the far-red light absorbing form of phytochrome. Therefore, we
      discuss a new model for this reaction in plants. Since it is unlikely that yeast
      cells contain elements that distinguish between phytochrome A and B, we conclude
      that sequestering and dark reversion reflect intrinsic properties of phytochrome.

PMID- 7650039
TI  - Identification of plakoglobin domains required for association with N-cadherin
      and alpha-catenin.
AB  - Cadherins are calcium-dependent, cell surface glycoproteins involved in cell-cell
      adhesion. To function in cell-cell adhesion, the transmembrane cadherin molecule
      must be associated with the cytoskeleton via cytoplasmic proteins known as
      catenins. Three catenins, alpha-catenin, beta-catenin, and gamma-catenin (also
      known as plakoglobin), have been identified. The domain of the cadherin molecule
      important for its interaction with the catenins has been mapped to the COOH
      terminal 70 amino acids, but less is known about regions of the catenins that
      allow them to associate with one another or with the cadherin molecule. In this
      study we have transfected carboxyl-terminal deletions of plakoglobin into the
      human fibrosarcoma HT-1080 and used immunofluorescence localization and co
      immunoprecipitation to map the regions of plakoglobin that allow it to associate
      with N-cadherin and with alpha-catenin. Plakoglobin is an armadillo family member
      containing 13 weakly similar internal repeats. These data show that the alpha
      catenin-binding region maps within the first repeat and the N-cadherin-binding
      region maps within repeats 7 and 8.

PMID- 7650040
TI  - Functional coupling of glycosyl transfer steps for synthesis of gangliosides in
      Golgi membranes from neural retina cells.
AB  - The synthesis of the oligosaccharide of gangliosides is carried out in the Golgi
      complex by successive sugar transfers to proper glycolipid acceptors. To examine
      how the product of one glycosylation step couples with the next transfer step,
      the endogenous gangliosides of Golgi membranes from 14-day-old chick embryo
      retina were labeled from CMP-[3H]NeuAc or UDP-[3H]GalNAc or UDP-[3H]Gal in
      conditions which do not allow vesicular intercompartmental transport. After
      saturation of the endogenous acceptor capacity, labeling was mostly in the
      immediate acceptors of the corresponding labeled sugars. However, some labeled
      intermediates progressed to more glycosylated gangliosides if the membranes were
      incubated in a second step in the presence of the necessary unlabeled sugar
      nucleotides. This was particularly evident in the case of membranes incubated
      with UDP-[3H]Gal, in which most of the [3H]Gal-labeled lactosylceramide
      synthesized in the first step was converted to GM3 and GD3, or to GM2 or to GD1a
      in a second incubation step in the presence of unlabeled CMP-NeuAc alone, or
      together with UDP-GalNAc, or together with UDP-Gal plus UDP-GalNAc, respectively.
      Conversion was time dependent and dilution-independent. Since prior reports using
      brefeldin A indicate that transfer steps catalyzed by GalNAc-T, Gal-T2, and Sial
      T4 localize in the trans-Golgi network (TGN), our results lead to the following
      major conclusions: (a) transfer steps catalyzed by GalNAc-T, Gal-T2, and Sial-T4
      colocalize and are functionally coupled in the TGN; (b) proximal Golgi Gal-T1,
      Sial-T1, and Sial-T2, and their corresponding glycolipid acceptors, extend their
      presence to the TGN, and (c), GalNAc-T and Sial-T2 compete for a common pool of
      acceptor GM3 in the synthesis of GM2 and GD3.

PMID- 7650041
TI  - A domain of the gene 4 helicase/primase of bacteriophage T7 required for the
      formation of an active hexamer.
AB  - The bacteriophage T7 gene 4 protein, like a number of helicases, is believed to
      function as a hexamer. The amino acid sequence of the T7 gene 4 protein from
      residue 475 to 491 is conserved in the homologous proteins of the related phages
      T3 and SP6. In addition, part of this region is conserved in DNA helicases such
      as Escherichia coli DnaB protein and phage T4 gp41. Mutations within this region
      of the T7 gene 4 protein can reduce the ability of the protein to form hexamers.
      The His475-->Ala and Asp485-->Gly mutant proteins show decreases in nucleotide
      hydrolysis, single-stranded DNA binding, double-stranded DNA unwinding, and
      primer synthesis in proportion to their ability to form hexamers. The mutation
      Arg487-->Ala has little effect on oligomerization, but nucleotide hydrolysis by
      this mutant protein is inhibited by single-stranded DNA, and it has a higher
      affinity for dTTP, suggesting that this protein is defective in the protein
      protein interactions required for efficient nucleotide hydrolysis and
      translocation on single-stranded DNA. Gene 4 protein can form hexamers in the
      absence of a nucleotide, but dTTP increases hexamer formation, as does dTDP, to a
      lesser extent, demonstrating that the protein self-association affinity is
      influenced by the nucleotide bound. Together, the data demonstrate that this
      region of the gene 4 protein is important for the protein-protein contacts
      necessary for both hexamer formation and the interactions between the subunits of
      the hexamer required for coordinated nucleotide hydrolysis, translocation on
      single-stranded DNA, and unwinding of double-stranded DNA. The fact that the gene
      4 proteins form dimers, but not monomers, even while hexamer formation is
      severely diminished by some of the mutations, suggests that the proteins
      associate in a manner with two separate and distinct protein-protein interfaces.

PMID- 7650043
TI  - Premature weaning in east Bhutan: only if mother is pregnant again.
AB  - The relationship between breast-feeding and subsequent pregnancy in East Bhutan
      is examined, against the background of local attitudes to family planning. Ninety
      eight mothers who had given birth 30-36 months earlier were interviewed.
      Semisolid supplementary feeding was introduced at a median age of 3 months.
      Median total duration of breast-feeding was 28 months, and day and night breast
      feeding on demand was continued throughout. Median duration of postpartum
      amenorrhoea was 12 months, and was associated with the timing of the introduction
      of supplementary foods. There was a significant association between the
      occurrence of a subsequent pregnancy and early termination of breast-feeding. The
      relationships between breast-feeding pattern and pregnancy interval are complex,
      and their relative influence changes with time. During the first year postpartum,
      infertility during lactational amenorrhoea is important. During the second year
      there is a strong negative effect on lactation from the next pregnancy. The only
      important reason for ceasing to breast-feed within 2 years seems to be a new
      pregnancy.

PMID- 7650044
TI  - Is menopause withering away?
AB  - Menopause (cessation of menstruation) and the period surrounding it
      (climacterium) are often defined retrospectively by asking a woman the date of
      her last menstrual period (LMP). Based on a survey of 2000 women aged 45-64 in
      1989 in Finland, this study examines (1) the relation between these definitions
      and women's own definition of their climacteric status and of the cessation of
      menstruation and (2) the effect of menopausal and postmenopausal hormone therapy
      and hysterectomy on the definition of menopause and climacterium. Agreement of
      the woman's own definition of her climacteric status and interval since LMP was
      25% among current hormone users, 41% among hysterectomised women and 64% among
      those who were neither currently using hormones nor had been hysterectomised.
      Current hormone users defined the climacteric phase as longer than their LMP
      suggested. Current hormone use and hysterectomy had little effect on reported
      final cessation of menstrual periods. It is concluded that hysterectomy and
      hormone therapy shape women's thinking about the end of reproductive life, blur
      the concepts of menopause and postmenopause and confuse the measurement of age at
      menopause.

PMID- 7650042
TI  - The growth-dependent expression of angiotensin II type 2 receptor is regulated by
      transcription factors interferon regulatory factor-1 and -2.
AB  - Angiotensin II type 2 (AT2) receptor is abundantly and widely expressed in fetal
      tissues but present only in restricted tissues in the adult such as brain and
      atretic ovary. This receptor is speculated to be involved in tissue growth and/or
      differentiation. To elucidate the molecular mechanism of growth-regulated AT2
      receptor expression, we cloned the mouse AT2 receptor genomic DNA and studied its
      promoter function in mouse fibroblast-derived R3T3 cells, which express AT2
      receptor in the confluent, quiescent state but very low levels of the receptor in
      actively growing state. Promoter/luciferase reporter deletion analysis of AT2
      receptor in R3T3 cells showed that the putative negative regulatory region is
      located between the positions -453 and -225, which plays an important role in the
      transcriptional control of AT2 receptor gene expression along with the cell
      growth. We identified the interferon regulatory factor (IRF) binding motif in
      this region using DNase foot-printing analysis and demonstrated that IRF binding
      oligonucleotide treatment increased the AT2 receptor expression in growing R3T3
      cells but not in confluent cells. Furthermore, by antisense treatment, we
      demonstrated that IRF-2 attenuated the AT2 receptor expression in both growing
      and confluent R3T3 cells, whereas IRF-1 enhanced AT2 receptor expression in the
      confluent cells only. Consistent with this result, gel mobility shift assay
      demonstrated that growing R3T3 cells exhibited only IRF-2 binding, whereas
      confluent cells exhibited both IRF-1 and IRF-2 binding. Furthermore, we observed
      using reverse transcription-polymerase chain reaction that the IRF-1 mRNA
      expression was more abundant in confluent cells than growing cells, whereas IRF-2
      expression did not change with R3T3 cell growth. We conclude that, in confluent
      cells, the enhanced expression of IRF-1 antagonizes the IRF-2 effect and
      increases the AT2 receptor expression. We speculate that these transcriptional
      factors influence cell growth in part by regulating AT2 receptor expression.

PMID- 7650045
TI  - The impact on fertility of contraceptive failure in China in the 1980s.
AB  - Contraceptive failure was an important determinant of fertility in China in the
      1980s. Based on the data from the China Two-per-Thousand Fertility Survey, this
      study shows that about 7% of the general fertility rate of currently married
      women aged 15-49 for a 12-month period is attributed to contraceptive failure,
      mainly due to the high failure rate associated with IUD use. A number of
      demographic characteristics are associated with contraceptive use, and with
      contraceptive failure and its outcome. Relevant socioeconomic differentials are
      also identified.

PMID- 7650046
TI  - The adaptive significance of social synchronisation of ultradian behaviour
      cycles: a computer model.
AB  - Daily behaviour patterns in a hunter-gatherer community of Colombian Indians show
      that individual activities are regulated by ultradian behaviour cycles of about 2
      hr and that these cycles can be synchronised by social interaction. A computer
      model was developed which simulated an artificial community and generated dynamic
      portraits of locomotor activity and social aggregation similar to those of the
      observed community of Colombian Indians. Social phase-locking of ultradian
      behaviour cycles occurred, contributing to the safety of group members and their
      economy of effort in gathering and related activities. Social synchronisation of
      ultradian behaviour cycles may also have occurred in early hominid groups.

PMID- 7650047
TI  - Significance of beliefs and values in predicting fertility and contraceptive
      behaviour in Pakistan.
AB  - A comparative study of 1100 women aged 25-45 years, users and non-users of modern
      methods of contraception, in the urban centres of Lahore and Faisalabad was
      conducted in 1991. The objective of the study was to investigate reproductive
      behaviour and the extent to which social, cultural and attitudinal variables,
      such as beliefs and values about family life, religiosity and fatalism, influence
      the fertility decision-making process. Preferences for smaller families were
      found to be consistently associated with modern attitudes and behaviour towards
      family and religious values and obligations. Family income, husband's occupation
      and religiosity offered no explanation of reproductive behaviour. It is concluded
      that cultural setting and tradition exert an important influence on reproductive
      behaviour, independent of economic development.

PMID- 7650048
TI  - Unmet need for family planning in Jamaica.
AB  - This study updates and extends estimates for unmet need and total demand for
      family planning for Jamaican women in the reproductive age group, 15-49. The
      findings suggest that, as yet unmet need for family planning was 22.7%, compared
      to 16% previously estimated.

PMID- 7650049
TI  - Early marriage among rural and urban females of south India.
AB  - Data on 2972 marriages in rural areas and 1180 marriages in urban areas of North
      Arcot Ambedkar district of South India, during 1982-88, were analysed. The mean
      age at marriage of females was 18.6 in the rural and 19.6 in the urban area. The
      proportion of females married before attaining the legal age of 18 years was
      higher among the rural community (36.8%) than in the urban community (28.9%).
      Univariate analysis revealed an association between early age at marriage and the
      socioeconomic variables religion, caste, consanguinity, marital distance, spousal
      age difference, education and occupation of both bride and bridegroom, and
      socioeconomic status of the family. Multivariate analysis showed an independent
      relationship of marital distance and bridegroom's occupation with early age at
      marriage of females in the rural area alone and the bridegroom's education in the
      urban area alone. Consanguinity, spousal age difference and bride's education
      were found to be independently related with early age at marriage of females in
      both rural and urban areas.

PMID- 7650050
TI  - Effects of inbreeding on marriage payment in north India.
AB  - This study examines the relationships between consanguineous marriages and
      marriage payment, using data from two Muslim qaums living in urban and rural
      areas in Aligarh District, Uttar Pradesh, North India. Qaum and locality were
      found to have no significant association with the dowry system. Marriage payment
      is less common in consanguineous than in non-consanguineous marriages. However,
      the association between marriage payment and the type of marriage is significant
      at p < 0.001. The dowry system is more prevalent among the higher socioeconomic
      groups, while the bride-wealth system is more common among the lower
      socioeconomic groups.

PMID- 7650051
TI  - Factors affecting choice of sterilisation among low income women in Paraiba,
      Brazil.
AB  - Despite the absence of a family planning programme, the prevalence of
      sterilisation in Brazil has increased substantially, such that it is used by
      relatively young women in poor areas of the country. Sterilisation is influenced
      more by the characteristics of the health service than by socioeconomic
      characteristics of the population.

PMID- 7650052
TI  - Fertility and family planning in African cites: the impact of female migration.
AB  - This study uses data from thirteen Demographic and Health Surveys to examine
      effects of female migration on fertility in African cities. Contrary to
      expectations, migration from villages and towns in the 1980s and 1990s reduced
      total fertility rates in African cities by about one birth, from an estimated
      average of 5.55 in the absence of migration to 4.59. New arrivals experience much
      lower fertility in their first few years in cities than long term residents of
      similar age and parity. This results from the initial unmarried status of most
      migrants, high levels of spousal separation among new arrivals who are married,
      dramatic increases in use of modern methods of contraception after 2 years in
      cities, and continuation of traditionally long durations of postpartum
      abstinence. Accommodation of additional migrants thus appears consistent with
      efforts to reduce fertility in cities. Moreover, prospects for increased
      contraceptive prevalence in Africa may depend heavily on changes in population
      distribution that influence the demand for children, specifically movement to
      cities.

PMID- 7650053
TI  - Androgen effects on women's gendered behaviour.
AB  - Test of the applicability of the hormonal theory of sex-dimorphic behaviour to
      adult women is achieved in this study by assembling measures of prenatal and
      adult androgen exposure, and a broad measure of gendered behaviour on a sample of
      white women aged 27-30. Androgen exposure in the second (and no other) trimester
      of fetal life, combined with and in interaction with adult androgens,
      masculineses women's behaviour and explains a substantial proportion of the
      within-sex variance in women's adult gendered behaviour.

PMID- 7650054
TI  - EGF-induced increase in diacylglycerol, choline release, and DNA synthesis is
      extracellular calcium dependent.
AB  - Previous studies have demonstrated a strict extracellular Ca2+ dependence for the
      G0 to G1 and G1 to S transition in growth factor-treated T51B rat liver cells
      that is associated with increased levels of protein kinase C activity.
      Consequently, we have examined these cells for changes in phospholipid-derived
      second messengers in response to epidermal growth factor (EGF) and thrombin in
      order to determine which signals are generated during the initiation of the G0 to
      G1 transition. Thrombin is coupled to a phosphoinositide hydrolyzing
      phospholipase C, as we have found a rapid Ca(2+)-independent increase in the
      levels of inositol 1,4,5-trisphosphate (Ins[1,4,5]P3), inositol 1,4-bisphosphate
      (Ins[1,4]P2), and inositol 4-monophosphate (Ins[4]P), as well as a concomitant,
      transient elevation in diacylglycerol. No changes in either intracellular or
      extracellular choline metabolites, or an increase in DNA synthesis, were found in
      response to thrombin. By contrast, treatment of T51B cells with EGF results in a
      slower, more prolonged extracellular Ca(2+)-dependent increase in both [3H]
      glycerol radiolabeled diacyl-glycerol, and diacylglycerol mass, an increase in
      choline release into the extracellular medium, and eventually a substantial DNA
      synthesis. We were, however, unable to detect any changes in phosphatidylinositol
      (PtdIns) turnover, either by accumulation of inositol phosphates or by changes in
      phospholipids in response to EGF. These results indicate that DNA synthesis can
      readily occur in the absence of stimulated PtdIns turnover, and that PtdIns
      turnover is not sufficient in itself or necessary to induce DNA synthesis and is
      not necessary for a Ca(2+)-dependent increase in diacylglycerol. Moreover, we
      have demonstrated that the extracellular Ca(2+)-dependent increase in
      diacylglycerol levels in response to EGF is associated with an increase in
      extracellular choline release, which is indicative of an activation of a
      phosphatidylcholine-linked phospholipase D. These results suggest that
      diacylglycerol sources other than PtdIns's may be important in the extracellular
      Ca(2+)-dependent regulation of EGF-mediated cell replication.

PMID- 7650055
TI  - Competition between c-fos and 1,25(OH)2 vitamin D3 in the transcriptional control
      of type I collagen synthesis in MC3T3-E1 osteoblastic cells.
AB  - Interaction between c-fos and 1,25(OH)2 vitamin D3 (VD) on the type I collagen
      synthesis was studied. VD inhibited collagen synthesis and type I collagen mRNA
      expression in MC3T3-E1 osteoblastic cells. In contrast, VD reversed the
      inhibition of collagen synthesis and mRNA expression of the c-fos transfectants
      that overexpressed c-fos gene to a comparable level as those of the control
      transfectants. The gel shift assay showed the vitamin D receptor (VDR) complex
      binding to vitamin D responsive element (VDRE) was inhibited under constitutively
      expressed c-fos gene, suggesting that c-fos gene product, c-Fos, may inhibit the
      binding of VDR complex to VDRE by making a c-Fos-VDR complex. The result suggests
      the existence of a fine tuning between c-fos and VD in the bone metabolism which
      may be relevant to the pathogenesis of rheumatoid bone lesion.

PMID- 7650056
TI  - On the mechanisms of the growth-promoting effect of prostaglandins in
      hepatocytes: the relationship between stimulation of DNA synthesis and signaling
      mediated by adenylyl cyclase and phosphoinositide-specific phospholipase C.
AB  - While many observations indicate that prostaglandins may act as positive
      regulators of hepatocyte proliferation, the underlying mechanisms are not known.
      We have examined some of the signal pathways in the growth response induced by
      prostaglandins in hepatocytes, with particular focus on adenylyl cyclase and
      phosphoinositide-specific phospholipase C. Adult rat hepatocytes were cultured as
      primary monolayers in serum-free medium in the presence of EGF and insulin. PGE2
      or PGF2 alpha (added 0-3 h after plating) enhanced the incorporation of [3H]
      thymidine into DNA (measured at 50 h); at 100 microM the stimulation was about
      threefold PGI2 and PGD2 also showed significant but smaller stimulatory effects.
      No significant increase in the level of cyclic AMP (cAMP) was detected in
      response to any of the prostaglandins. Low concentrations of glucagon (0.1-10
      nM), a potent activator of hepatic adenylyl cyclase, or 8-bromo-cAMP (0.1-10
      microM) enhanced the DNA synthesis. When 8-bromo-cAMP was used in maximally
      effective concentrations, no further stimulation was obtained by combining it
      with glucagon, whereas the effects of PGE2 and 8-bromo-cAMP were completely
      additive. All the prostaglandins also showed additivity with the effect of
      glucagon on the DNA synthesis. PGE2, PGF2 alpha, PGI2, and PGD2 increased
      intracellular inositol-1,4,5-trisphosphate (InsP3), with a relative order of
      efficacy roughly corresponding to their activity as stimulators of DNA synthesis.
      Increases in cytosolic free Ca2+, as measured in single cells, were elicited in a
      majority of the hepatocytes by all these prostaglandins at 1 microM. Supramaximal
      concentrations of vasopressin, a strong activator of phospholipase C in
      hepatocytes, acted additively with PGE2 on the DNA synthesis. Pretreatment of the
      hepatocytes with a concentration of pertussis toxin that prevented the inhibitory
      effect of PGE2 on glucagon-induced cAMP accumulation did not abolish the ability
      of PGE2 to stimulate the DNA synthesis. The results do not support a role for
      adenylyl cyclase activation in the stimulatory effect of prostaglandins on
      hepatocyte growth. While the data are compatible with an involvement of
      phosphoinositide-specific phospholipase C in the growth-promoting effect of
      prostaglandins in cultured rat hepatocytes, they suggest this may not be the sole
      mechanism.

PMID- 7650057
TI  - Control of matrix synthesis in isolated bovine chondrocytes by extracellular and
      intracellular pH.
AB  - The effects of extracellular and intracellular pH on matrix synthesis by isolated
      bovine chondrocytes were studied using radioisotope incorporation (35SO4 and 3H
      proline) and fluorescence techniques. Matrix synthesis exhibited a bimodal
      relation with decreased extracellular pH; with slight reductions (7.4 > pH >
      7.1), synthesis increased (by up to 50%), whereas in more acidic media (pH <
      7.1), synthesis was inhibited by up to 75% of control levels. The pHi was largely
      unchanged with extracellular acidity over the range producing stimulation of
      matrix synthesis but fell when exposed to the more acidic media shown to have an
      inhibitory action on matrix synthesis. The inhibition of matrix synthesis by
      lactic acid addition was unaffected by the lactic acid transporter alpha-CHC,
      suggesting H+ transport by this pathway is small. Direct imposition of a
      sustained intracellular acidosis (pHi = 6.65) using ammonium prepulse with
      amiloride inhibited matrix synthesis by about 20%. These results show that matrix
      synthesis by chondrocytes was affected by extracellular pH, an action which could
      not be entirely explained by changes to pHi.

PMID- 7650058
TI  - Laminarin sulfate mimics the effects of heparin on smooth muscle cell
      proliferation and basic fibroblast growth factor-receptor binding and mitogenic
      activity.
AB  - Heparin and heparin-like molecules may function, apart from their effect on
      hemostasis, as regulators of cell growth and neovascularization. We investigated
      whether similar effects are exerted by laminarin sulfate, an unrelated
      polysulfated saccharide isolated from the cell wall of seaweed and composed of
      chemically O-sulfated beta-(1,3)-linked glucose residues. Laminarin sulfate
      exhibits about 30% of the anticoagulant activity of heparin and is effective
      therapeutically in the prevention and treatment of cerebrovascular diseases. We
      characterized the effect of laminarin sulfate on interaction of the heparin
      binding angiogenic factor, basic fibroblast growth factor (bFGF), with a
      naturally produced subendothelial extra-cellular matrix (ECM) and with cell
      surface receptor sites. Laminarin sulfate (1-2 micrograms/ml) inhibited the
      binding of bFGF to ECM and to the surface of vascular smooth muscle cells (SMC)
      in a manner similar to that observed with heparin. Likewise, laminarin sulfate
      efficiently displaced both ECM- and cell-bound bFGF at concentrations as low as 1
      microgram/ml. Both laminarin sulfate and heparin efficiently induced restoration
      of bFGF receptor binding in xylosyltransferase-deficient CHO cell mutants
      defective in initiation of glycosaminoglycan synthesis. Moreover, laminarin
      sulfate elicited bFGF receptor activation and mitogenic response in heparan
      sulfate (HS)-deficient, cytokine-dependent lymphoid cells. These results indicate
      that laminarin sulfate effectively replaced the need for heparin and HS in the
      induction of bFGF receptor binding and signaling. In other experiments, laminarin
      sulfate was found to inhibit the proliferation of vascular SMC in a manner
      similar to that observed with heparin. These effects of laminarin sulfate may
      have potential clinical applications in diverse situations such as wound healing,
      angiogenesis, and atherosclerosis.

PMID- 7650059
TI  - Endothelin-1 induces gene expression through stimulation of endothelin type A
      receptors in normal rat kidney cells.
AB  - RNA blots of total cellular RNA isolated from quiescent and endothelin (ET-1)
      stimulated normal rat kidney (NRK) cells demonstrated that ET-1 induced the
      expression of c-jun, jun B, and c-fos mRNA in a time-dependent manner with
      maximal expression of mRNA by 1 hr after the addition of ET-1. Five hundred
      picomolar ET-1 was sufficient to induce maximal mRNA expression. These data
      agreed with saturation experiments which demonstrated that maximal binding of
      [125I]ET-1 was achieved at concentrations greater than 100 pM. The Kd and Bmax
      values for [125I]ET-1 binding to NRK membranes were 20.5 pM and 22.2 fmol/mg
      protein, respectively. Competition experiments for the binding of [125I]ET-1 to
      NRK membranes demonstrated that ET-1 was a more potent inhibitor (Ki = 0.047 nM)
      than ET-3 (Ki = 10.8 nM). No specific binding of [125I]ET-3 (40 or 500 pM) to NRK
      membranes could be observed. The expression of c-jun, jun B, and c-fos mRNA was
      inhibited by the endothelin type A receptor (ET)-selective antagonist, BQ-123.
      Thus, these data demonstrate that ET-1 mediates the expression of immediate
      response gene mRNA in NRK cells via the ETA receptor. ET-1 stimulation of NRK
      cells also upregulated EGF receptors, providing a possible mechanism for ET-1
      complementation of epidermal growth factor (EGF) mitogenicity in NRK cells.

PMID- 7650060
TI  - Release from quiescence stimulates the expression of integrin alpha 5 beta 1
      which regulates DNA synthesis in human fibrosarcoma HT1080 cells.
AB  - We show that integrin alpha 5 subunit expression is stimulated when human
      fibrosarcoma HT1080 cells are released from quiescence. The alpha 5 subunit mRNA
      level in quiescent HT1080 cells was increased 24 hr after their release by 10%
      fetal bovine serum-containing medium reaching a maximum of 2.5 fold on day 2.
      Similar levels of induction of cell-surface alpha 5 subunit protein as well as
      beta 1 subunit protein were also observed. This resulted in a significant
      increase of cell attachment to fibronectin. The serum stimulation also increased
      alpha 5 subunit promoter activity by twofold which was protein synthesis
      independent. Subsequent deletion of alpha 5 subunit promoter DNA showed that the
      cis-element responsible for the activation is located between -92 bp and the
      transcription start site. The promoter activity was not induced until 12 hr after
      the release. Comparison of the effect of a serum-free medium and a 10% fetal
      bovine serum-supplemented medium revealed that both the DNA synthesis and alpha 5
      subunit induction were independent of exogenous growth factors. The increased
      integrin alpha 5 beta 1 appears to function by reducing mitogenic activity since
      blockade of fibronectin binding to its receptor with a RGD peptide, a monoclonal
      anti-fibronectin antibody, or a monoclonal anti-alpha 5 subunit antibody during
      the release from quiescence significantly stimulated DNA synthesis. On the other
      hand, stable overexpression of the alpha 5 subunit resulted in decreased DNA
      synthesis.

PMID- 7650061
TI  - Cytoskeletal regulation of Caco-2 intestinal monolayer paracellular permeability.
AB  - An abnormal increase in intestinal paracellular permeability may be an important
      pathogenic factor in various intestinal diseases. The intracellular factors and
      processes that regulate and cause alteration of intestinal paracellular
      permeability are not well understood. The purpose of this study was to examine
      some of the intracellular processes involved in cytoskeletal regulation of
      intestinal epithelial paracellular permeability using the filter-grown Caco-2
      intestinal epithelial monolayers. Cytochalasin-b and colchicine were used to
      disrupt the cytoskeletal elements, actin microfilaments, and microtubules.
      Cytochalasin-b (5 micrograms/ml) and colchicine (2 x 10(-5) M) at the doses used
      caused marked depolymerization and disruption of actin microfilaments and
      microtubules, respectively. Cytochalasin-b-induced disruption of actin
      microfilaments resulted in perturbation of tight junctions and desmosomes and an
      increase in Caco-2 monolayer paracellular permeability. The cytochalasin-b
      induced disruption of actin microfilaments and subsequent changes in
      intercellular junctional complexes and paracellular permeability were not
      affected by inhibitors of protein synthesis (actinomycin-D or cycloheximide) or
      microtubule function (colchicine), but were inhibited by metabolic energy
      inhibitors (2,4-dinitrophenol or sodium azide). The cytochalasin-b-induced
      disturbance in Caco-2 actin microfilaments and intercellular junctional complexes
      and increase in paracellular permeability were rapidly reversed. The paracellular
      pathway "re-tightening" following cytochalasin-b removal was not affected by
      actinomycin-D, cycloheximide, or colchicine, but was inhibited by 2,4
      dinitrophenol and sodium azide. The colchicine-induced disruption of microtubules
      did not have significant effect on actin microfilaments, intercellular junctions,
      or paracellular permeability. These findings suggest that cytochalasin-b-induced
      increase in Caco-2 monolayer paracellular permeability was due to actin
      microfilament mediated perturbation of intercellular junctional complexes. The re
      tightening of paracellular pathways (following removal of cytochalasin-b)
      resulted from energy-mediated re-assembly of pre-existing actin microfilaments
      and intercellular junctional complexes. This re-closure process did not require
      protein synthesis or microtubule-mediated shuttling process.

PMID- 7650063
TI  - Secretion of plasminogen activator and lysosomal enzymes from mouse skeletal
      muscle: effect of denervation.
AB  - Levels of hydrolytic enzymes increase in skeletal muscle after denervation and
      their activities in the extracellular matrix appear to be important for
      interaction between muscle and nerve. Using enzymatic assays for beta
      glucuronidase, beta-galactosidase, and plasminogen activator, we show that
      secretion of these enzymes from mouse skeletal muscle increases after denervation
      and that drugs interfering with the secretory pathway or the reuptake of enzymes
      modulate this release. Thus, brefeldin A inhibited secretion of plasminogen
      activator activity and mannan increased secreted amounts of beta-glucuronidase,
      but not of beta-galactosidase, in denervated muscle. In innervated muscle,
      brefeldin A decreased secreted activity of plasminogen activator, but mannan had
      no effect on secretion of either beta-glucuronidase or beta-galactosidase.
      Furthermore, secretion of plasminogen activator was temperature dependent. These
      observations, together with previous studies, suggest that secretion of
      hydrolytic enzymes from adult skeletal muscle may be of physiological
      significance in nerve-muscle communication.

PMID- 7650062
TI  - Two major pathways of zinc(II) acquisition by human placental
      syncytiotrophoblast.
AB  - Uptake of zinc into placental villous syncytiotrophoblast is the first step in
      its transfer from mother to fetus. To help characterise physiologically
      significant pathways of zinc accumulation by these cells, we incubated cultured
      layers of syncytiotrophoblast cells derived from human near-term placental tissue
      with serum ultrafiltrate (containing the zinc complexed with low molecular mass
      serum constituents), dialysed serum (containing the zinc bound to the serum
      proteins) and whole serum, each of whose endogenous zinc was tracer-labelled with
      65Zn(II). Zinc label from both fractions of serum readily entered a rapidly
      labelled EDTA-sensitive cellular compartment, probably representing zinc bound to
      the outside cell surface and in accumulative fashion, an EDTA-resistant
      compartment, probably consisting largely of internalised cellular zinc. Movement
      of zinc into the EDTA-resistant pool was strongly temperature-dependent and did
      not occur via the EDTA-sensitive pool from either serum source. Transfer of zinc
      from the low molecular mass serum fraction into the EDTA-resistant pool was
      saturable, the concentration giving half-maximal rate being 1.2 mumol/l
      nonprotein-bound zinc. No nonsaturable component was detected. Zinc from the
      serum protein-bound fraction entered by a saturable component, already saturated
      at physiological total protein-bound zinc concentration, and by an apparently
      nonsaturable component, not appreciably accounted for by nonspecific fluid-phase
      endocytosis. The results show that zinc is acquired by placental
      syncytiotrophoblast from the low molecular mass serum zinc pool probably by a
      carrier-mediated process, and at least as importantly, from the zinc bound to
      serum protein, possibly by an endocytic mechanism.

PMID- 7650064
TI  - Two nuclear proteins in tracheal epithelial cells are recognized by antibodies
      specific to a squamous differentiation marker, sprI.
AB  - In cell-free translations of RNA from primary cultures of pig trachea surface
      epithelial cells we observed that a mRNA encoding a 20 kDa proline-rich protein
      (sPRP) was dramatically induced during culturing (Tesfaigzi et al., 1990,
      Biochem. Biophys. Res. Commun., 172:M1304-1309). This mRNA was not detected in
      tracheal tissue or in epithelial cells prior to culturing. Antisera were raised
      to synthetic peptide sequences corresponding to 23 amino acids on the C-terminus
      (C23-antiserum) and 29 amino acids on the N-terminus (N29 antiserum) of sPRP. On
      Western blot analysis, C23 antiserum reacted with a 20 kDa protein in cytosolic
      extracts from pig tracheal cells maintained in culture for 4 days. The reaction
      with the 20 kDa protein was inhibited by adding C23 peptide. Two nuclear proteins
      (66 and 70 kDa) obtained by micrococcal nuclease treatment of tracheal cell
      nuclei were detected on Western blots with C23 antiserum. These proteins were
      present in cells both before and after culturing. Sucrose gradient fractionation
      indicated that these nuclear proteins are associated with chromatin. Small
      amounts of the 66 and 70 kDa proteins were obtained from nuclear matrix
      fractions. These nuclear proteins also reacted with N29 antiserum. Since these
      proteins share similar epitopes with the N- and C-termini of sPRP, it is likely
      that the 20 kDa protein (sPRP) is part of these proteins. However, purification
      of the nuclear proteins followed by an amino acid sequence analysis is necessary
      to clarify whether sPRP is part of these proteins.

PMID- 7650065
TI  - Thermotolerance and nuclear protein aggregation: protection against initial
      damage or better recovery?
AB  - Heat-induced nuclear protein aggregation and subsequent disaggregation were
      measured in nonpreheated and preheated (thermotolerant) HeLa S3 cells. The effect
      of thermotolerance on the formation of and recovery from heat-induced nuclear
      protein aggregates was related to the cellular levels of hsp27, hsp60, hsp70,
      hsc70, and hsp90. Cells heated at different time points after the thermotolerance
      trigger showed various levels of protection against heat-induced nuclear protein
      aggregation. This protection, however, did not parallel the development and decay
      of thermotolerance on cell survival. The protection was maximal when the
      thermotolerance level already had started to decay. The level of protection
      against nuclear protein aggregation did however parallel the cellular level of
      hsp70 indicating that hsp70 may be involved in this process. At all stages during
      the development and decay, thermotolerant cells showed a more rapid recovery
      (disaggregation) from the heat-induced nuclear protein aggregates than non
      thermotolerant cells. The rates of disaggregation during development and decay of
      thermotolerance paralleled the cellular levels of hsp27 suggesting that hsp27 is
      somehow involved in this recovery process from heat-induced nuclear protein
      aggregates. The total cellular levels of none of the individual hsp's completely
      correlate with development and decay of thermotolerance, indicating that
      overexpression of any of these hsp's alone does not determine the level of
      thermotolerance. Clonogenic cell survival paralleled the rates of disaggregation,
      leading to the notion that recovery processes are the most important determinant
      for the thermotolerant state of HeLa S3 cells. The best correlation with
      clonogenic survival was found when both initial aggregation and subsequent
      disaggregation were taken into account, suggesting that the combined action of
      various hsp's in these two processes have to be included in thermotolerance
      development and decay.

PMID- 7650066
TI  - Identification of a chemotactic epitope in human transforming growth factor-beta
      1 spanning amino acid residues 368-374.
AB  - TGF-beta 1 plays a critical role in inflammatory and repair processes due in part
      to its ability to provide a potent chemotactic stimulus for inflammatory cells
      such as neutrophils and monocytes and for fibroblasts which initiate the
      fibrogenic response. In the present study, we have used synthetic oligopeptides
      representing the amino acid sequence of the 12.1 kDa monomer of human TGF-beta 1
      in an effort to identify a chemotactic epitope on the molecule. A seven residue
      peptide containing residues 368-374, Val Tyr Tyr Val Gly Arg Lys, was
      demonstrated to be capable of inducing chemotactic migration of human peripheral
      blood neutrophils, monocytes, monocyte leukemia cell line THP-1, and infant
      foreskin fibroblasts. Furthermore, larger peptides from the carboxy-terminal
      portion of TGF-beta 1 that contained residues 368-374 also induced migration of
      these cell types. None of the peptides representing the complete amino acid of
      TGF-beta 1 monomer were able to compete with [125I]hrTGF-beta 1 for binding to
      TGF-beta cell surface receptors or fibroblasts or THP-1 cells. Implications of
      these observations are discussed.

PMID- 7650067
TI  - Laminin responsiveness is associated with changes in fibroblast morphology,
      motility, and anchorage-independent growth: cell system for examining the
      interaction between laminin and EGF signaling pathways.
AB  - Laminin can influence the adhesion, differentiation, and motility of several cell
      types, including epithelial and neural cells. In addition, laminin, which
      contains an epidermal growth factor (EGF)-like motif, can stimulate DNA synthesis
      in fibroblasts possessing the EGF receptor, but laminin does not compete for EGF
      binding. To further investigate laminin action in fibroblasts, and the
      relationship between laminin and EGF receptor function, we have developed a
      system wherein cells containing laminin-binding activity were cloned from a mouse
      fibroblast cell line (B82L-wt) that cannot adhere to laminin but that have been
      transfected with the wild-type human EGF receptor. Although only the isolated
      clones can efficiently attach to laminin-coated plates, all the cells can adhere
      to plastic, fibronectin, and collagen l, and all exhibit comparable levels of
      cell surface-associated laminin. Ligand-binding assays showed that the cells with
      laminin attachment activity possess high-affinity EGF binding (Kd approximately
      0.4 nM), and all express a similar level of the human EGF receptor. However, when
      compared to the B82L-wt cells, the cells with laminin-binding activity exhibit
      altered morphology, anchorage-independent growth, and motility. Specifically, the
      morphology of the fibroblasts possessing laminin binding activity appears more
      elongated and they spread more extensively on plastic plates. Analysis of their
      growth in soft agar revealed that the clones have a 2-5-fold increase in colony
      formation in comparison to the B82L-wt cells. The cells possessing laminin
      attachment ability also exhibit laminin-induced motility, and this movement is
      directional (chemotaxis) rather than random (chemokinesis), indicating functional
      laminin receptors and signaling pathways. To examine the specific laminin
      receptors involved in these effects, the influence of anti-integrin subunit
      antibodies on cell adhesion and migration was evaluated. These studies showed
      that an anti-alpha 6 integrin antibody can completely inhibit the clonal cells'
      attachment and migration to laminin, and anti-alpha 6 immunoblots revealed that
      only the clones express measurable levels of alpha 6. These data indicate that
      alpha 6-containing integrins contribute to the laminin-mediated attachment and
      motility of these clones and that this system may also influence the morphology
      and anchorage-independent growth of these fibroblasts. In addition, these cells
      provide a unique system for examining the interaction between EGF and laminin
      receptor action.

PMID- 7650068
TI  - Lymphocyte transendothelial migration toward smooth muscle cells in interleukin-1
      beta-stimulated co-cultures is related to fibronectin interactions with alpha 4
      beta 1 and alpha 5 beta 1 integrins.
AB  - We previously reported infiltration of immune-inflammatory cells in coronary
      arteries from cardiac allografts, associated with increased endothelial and
      smooth muscle cell fibronectin synthesis regulated by interleukin (IL)-1 beta. We
      now investigate, using a porcine endothelial-smooth muscle cell co-culture
      system, whether IL-1 beta-stimulated fibronectin production is functionally
      important in lymphocyte transendothelial migration. Lymphocytes were harvested
      from porcine peripheral blood and, in the unactivated state or following
      activation with phorbol myristic acetate (PMA) and IL-2, were characterized by
      fluorescence-activated cell sorter (FACS) analysis and added to a confluent
      endothelial monolayer on the upper chamber of a transwell system. Endothelial
      cells, as well as smooth muscle cells (in the bottom of the chamber), were
      stimulated with IL-1 beta. Then transendothelial lymphocyte migration was
      determined in the presence of CS1 and RGD (fibronectin) peptides, blocking alpha
      4 beta 1 and alpha 5 beta 1 integrin receptors on lymphocyte surfaces,
      respectively. A 55-70% inhibition of lymphocyte migration was observed when
      compared to control peptides. The combination of CS1 and RGD peptides did not
      significantly enhance the inhibitory effect of either peptide alone. A similar
      decrease in lymphocyte transendothelial migration toward smooth muscle cells was
      documented using a monoclonal antibody to cellular fibronectin. Furthermore,
      using smooth muscle cell conditioned medium, we reproduced the enhanced
      transendothelial lymphocyte migration as well as the inhibition with blocking
      peptides or fibronectin antibodies. Our data suggest that cytokine-mediated
      fibronectin synthesis in vascular cells recruits inflammatory cells through
      interactions of specific peptides with cell surface alpha 4 beta 1 and alpha 5
      beta 1 integrins.

PMID- 7650069
TI  - Nucleolar p120 is expressed as a delayed early response gene and is inducible by
      DNA-damaging agents.
AB  - Regulation of the expression of the growth-related nucleolar p120 protein was
      examined in serum-deprived and stimulated nontransformed and SV40-transformed WI
      38 human fibroblasts. In quiescent cells, transcriptional activity of the p120
      gene was very low or undetectable, and the steady-state levels of the p120 mRNA
      and the p120 protein were also negligible. The transient expression of the p120
      gene in the cell cycle was detected in middle G1-phase after the expression of
      the early response genes and before the expression of the DNA-synthesis genes.
      Protein synthesis was required for the induction of p120 expression in serum
      stimulated cells. The increased level of p120 mRNA in middle G1-phase was
      attributed to an increased transcription rate of the p120 gene, and not to a
      change in p120 mRNA stability. The calculated half-life of p120 mRNA was
      unchanged (1.8 +/- 0.2 hr) in all four cell conditions tested; i.e., in middle G1
      or S-phase cells and in exponentially growing normal or transformed cells.
      Transcription rate of the p120 gene was correlated with the steady-state levels
      of either p120 protein or p120 mRNA. A sharp increase in p120 mRNA level occurred
      in both normal and transformed cells treated with actinomycin D used to examine
      p120 mRNA stability. This induction of p120 mRNA expression was seen in early G1
      phase, but not in quiescent cells, or in middle to late G1-phase when cells
      expressed the highest level of p120 mRNA. The same expression pattern was seen by
      treatment with chlorambucil, another DNA-damaging agent. The conclusions of these
      studies are that the expression of p120 (1) is serum inducible in a fashion
      characteristic of the delayed early response gene products, (2) requires the
      presence of newly synthesized proteins, (3) is regulated transcriptionally, and
      (4) can be induced by DNA-damaging agents.

PMID- 7650071
TI  - Ergometrine and methylergometrine tablets are not stable under simulated tropical
      conditions.
AB  - OBJECTIVES: This study is part of a programme on reduction of postpartum
      haemorrhage (PPH). Ergometrine and methylergometrine have a favourable effect on
      both blood loss and maternal morbidity and mortality and oral preparations were
      regarded as a possible treatment for use in tropical countries. The stability of
      oral preparations of the two ergometrine compounds under tropical conditions was
      unknown and was therefore examined in this study. STUDY METHODS: The
      'experimental shelf lives' of ergometrine and methylergometrine tablets were
      examined by exposing the tablets to seven artificially controlled conditions.
      Samples were analysed by high performance liquid chromatography at nine different
      sampling times over a period of 1 year to determine the content of ergometrine
      and methylergometrine. RESULTS: Under refrigeration (test I), less than 90% of
      the stated amount of active ingredient was found in the tablets after 14 weeks in
      the case of ergometrine and 21 weeks in the case of methylergometrine. When
      stored in the dark at 40 degrees C and 75% relative humidity (test VI), the
      tablets fall outside accepted specification (= 90-110% of state amount of active
      ingredient) within 3 weeks in the case of ergometrine and 21 weeks in the case of
      coated methylergometrine tablets. The stability of uncoated ergometrine tablets
      was far less than that of coated methylergometrine tablets. Instability worsened
      under extreme humid conditions (test IV and VI), and hot conditions (test V), for
      both ergometrine and methylergometrine. From week 31 onwards the coating did not
      seem to protect the compound anymore, irrespective of the condition of exposure.
      CONCLUSIONS: Tropical conditions make the tablets unstable with humidity as the
      main adverse factor. The sugar-coated methylergometrine tablets are more stable
      under humid/hot conditions than the non-coated ergometrine tablets. Under all
      simulated conditions both oral ergometrine and methylergometrine tablets are
      unstable.

PMID- 7650070
TI  - Pharmacokinetic comparison of oral and local action transcutaneous flurbiprofen
      in healthy volunteers.
AB  - Flurbiprofen is a propionic acid-derived non-steroidal anti-inflammatory drug
      (NSAID) used widely in the treatment of rheumatism and non-arthritic pain. The
      pharmacokinetics of topically and orally administered flurbiprofen were compared
      in a two-part, open study involving healthy adult volunteers. In the first (cross
      over) part of the study, 12 Caucasians were randomized to receive either a single
      oral dose of 50 mg flurbiprofen or a single topical application of a novel 40 mg
      flurbiprofen-containing patch on the right wrist for 12 h. In the second part of
      the study, each subject applied a flurbiprofen-containing patch twice daily to
      the same wrist for 7 days. Plasma concentrations of flurbiprofen and urinary
      concentrations of the NSAID and its metabolites were measured by high-performance
      liquid chromatography assay, to enable comparison of the pharmacokinetic
      parameters for delivery of the drug by both routes. Maximum concentrations of the
      NSAID in plasma (Cmax) were much lower after a single application of the topical
      40 mg flurbiprofen patch than after a single oral dose of 50 mg of the NSAID
      (mean +/- SD: 43 +/- 16 ng/ml versus 5999 +/- 1300 ng/ml, respectively). After
      repeated application of the topical patch, Cmax increased only slightly to 103 +/
      57 ng/ml. The mean relative bioavailability of flurbiprofen from the patch was
      3.5 +/- 1.7%, calculated from plasma area under the curve data and 4.4 +/- 2.8%
      from urinary excretion data.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7650072
TI  - Oxytocin and desamino-oxytocin tablets are not stable under simulated tropical
      conditions.
AB  - OBJECTIVES: This study is part of a programme on reduction of postpartum
      haemorrhage. Buccal oxytocin and desamino-oxytocin administration with a
      favourable effect on both blood loss and maternal morbidity and mortality were
      regarded as possible treatments for use in tropical countries. The stability of
      buccal oxytocin and desamino-oxytocin under tropical conditions was unknown and
      therefore tested in this study. STUDY METHODS: The 'experimental shelf lives' of
      buccal oxytocin and desamino-oxytocin were examined by exposing the tablets to
      seven artificially controlled conditions. Samples were analysed by high
      performance liquid chromatography to determine the content of oxytocin and
      desamino-oxytocin at nine different times during the period of 1 year. RESULTS:
      Oxytocin and desamino-oxytocin are fairly stable under refrigeration. Instability
      for both drugs was detectable after 20 weeks' storage under humid conditions,
      independent of temperature. Desamino-oxytocin is more sensitive to light
      exposure; its concentration declines to 55.6% of the stated amount after 1 year
      of exposure to light compared to 85% in the case of oxytocin. Oxytocin packaged
      as supplied by the manufacturer were stable for 21 weeks when exposed to
      simulated humid (75% relative humidity) conditions. At 40 degrees C and 25%
      relative humidity there is no difference in stability between tablets in sealed
      aluminium packs as supplied by the manufacturer and unpackaged tablets.
      CONCLUSIONS: Tropical conditions make oxytocin and desamino-oxytocin tablets
      unstable, with humidity as the most adverse factor. The oxytocin tablets were
      partially protected from the harmful effect of humidity by sealed aluminium
      package.

PMID- 7650073
TI  - The placebo response: friend or foe?

PMID- 7650074
TI  - Medicine as an agency of social control: Part Four.

PMID- 7650075
TI  - Monitoring plasma levels of fluphenazine during chronic therapy with fluphenazine
      decanoate.
AB  - This study was conducted to examine the interpatient variability in steady-state
      plasma concentrations of fluphenazine by repeat depot intramuscular
      administration, and to determine the relationship between these concentrations
      and clinical state. Steady-state pre-dose concentrations of fluphenazine in
      plasma were measured using a sensitive and specific gas chromatography/mass
      spectrometry (GC/MS) assay in 24 patients with schizophrenia who were receiving
      continuous treatment with depot intramuscular fluphenazine decanoate. Clinical
      response was measured using the Andreasen Scale for positive and negative
      symptoms. Steady-state plasma concentrations of fluphenazine ranged from
      undetectable (< 0.1 ng/ml) to 27.9 ng/ml, with a median of 0.5 ng/ml. No
      significant associations were found between plasma concentration and dosage, or
      age and sex of the patient. Steady-state plasma concentrations in patients taking
      anticholinergic agents were significantly higher than in patients not receiving
      such drugs (P < 0.05 by Mann-Whitney U-test). Poorer control, expressed as the
      sum of the negative symptom scores or the sum of the positive and negative
      symptom scores, was related to higher log transformed plasma concentration of
      fluphenazine and higher fluphenazine decanoate dosage. The log transformed plasma
      concentrations of fluphenazine and the fluphenazine decanoate dosages were weakly
      related. Patients receiving another antipsychotic drug in addition to
      fluphenazine decanoate tended to have poorer clinical control and higher dosages
      of fluphenazine decanoate. These results indicate the useful role that plasma
      level monitoring can fulfil in identifying patients who are therapy-resistant
      despite high plasma levels.

PMID- 7650076
TI  - Antipsychotic drugs and tardive dyskinesia: preliminary results in an adolescent
      psychiatric ward.
AB  - The systematic study of antipsychotic-induced movement disorders in young
      psychiatric patients is very sparse. We assessed the presence of tardive
      dyskinesia in an adolescent in-patient psychiatric ward. Eighteen per cent (3/17)
      exhibited either pronounced or subtle signs of tardive dyskinesia. Our study
      suggests that young psychiatric patients may develop signs of tardive dyskinesia
      even though they are exposed to relatively short-term neuroleptic treatment and
      at dosages that are relatively low. We advocate frequent and systematic
      monitoring of adolescent patients taking antipsychotic drugs in order to minimize
      the emergence of this long-term, troublesome complication of neuroleptic drugs.

PMID- 7650077
TI  - Prospective evaluation of ten methods for estimating creatinine clearance in
      children with varying degrees of renal dysfunction.
AB  - The objective of this study was to evaluate ten methods for calculating
      creatinine clearance (Clcr) in children with renal dysfunction. The design was a
      prospective, comparative study using 24-h urinary Clcr as the criterion standard.
      Twenty-two children (age 7-16 years old) were studied. Urinary Clcr ranged from 0
      to 161 ml/min/1.73 m2. Calculated Clcr and 24-h urinary Clcr were evaluated
      statistically. Linear regression analysis, nominal frequency, and mean relative
      error were used to rank the methods. Children were stratified based on gender and
      renal function. None of the methods correlated well when Clcr > 100 ml/min/1.73
      m2. Predictive performance deteriorated as Clcr decreased. Simple methods using
      height and serum creatinine were best. Clcr (ml/min/1.73 m2) = (0.52 x height
      (cm)/serum creatinine)--3.6 was the best equation for estimating Clcr in our
      patient population consisting of children over 7 years of age with stable serum
      creatinine.

PMID- 7650078
TI  - Assessing the effectiveness of X-ray contrast media for abdominal computed
      tomographic examinations: comparison of four low-osmolality agents.
AB  - The objective of this investigation was to assess the effectiveness of four
      iodinated X-ray contrast media for abdominal computed tomographic (CT)
      examinations. Fifty-three patients were prospectively randomized to receive
      iohexol 300 mgI/ml (100 ml, n = 17), ioversol 320 mgI/ml (100 ml, n = 13),
      iopromide 300 mgI/ml (75 ml, n = 12), or iopentol 300 mgI/ml (100 ml, n = 11) to
      perform a dynamic contrast-enhanced abdominal CT. Image-enhancement profiles for
      the liver, aorta, and vena cava were studied. The maximum liver enhancement, the
      time to maximum liver enhancement, and the area under the hepatic enhancement
      time curve (AUC) were determined for each examination. Liver-enhancement profile
      showed significant differences between the four contrast agents, with lower
      values for iopromide towards the final part of the CT examination (P < 0.05).
      Hepatic peak values were attained earlier for iopromide, although these were
      lower than those produced by any other of the agents evaluated in this study.
      Iopentol produced fast and intense hepatic peaks. Consequently, high AUC values
      were obtained with iopentol, low values were obtained with iopromide (P < 0.05),
      although this can be explained by the lower amount of contrast medium contained
      in the commercial vial and administered to the patient (75 ml vs 100 ml). When
      normalized to a 100 ml dose, the AUC value for iopromide becomes even higher than
      the average of the other three agents (P = 0.05). Ioversol, although available
      and administered as a more concentrated solution (320 mg/ml), was comparable to
      the less concentrated iohexol and iopentol (300 mgI/ml).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7650079
TI  - Prevalence of hypercholesterolaemia and coronary heart disease risk factors among
      southeast Asian refugees in a primary care clinic.
AB  - The National Cholesterol Education Program's guidelines for the detection,
      evaluation, and treatment of high serum cholesterol in adults were employed in
      screening 155 Southeast Asian refugees in a primary care clinic in Seattle,
      Washington. In order to determine the need for a therapeutic intervention,
      information also was collected on the presence of other coronary heart disease
      (CHD) risk factors. Male gender (39%), cigarette smoking (27%) and hypertension
      (26%) were the most common CHD risk factors; diabetes mellitus, obesity, a family
      or prior history of CHD or cerebral/peripheral vascular disease were each noted
      in less than 10%. The mean serum total cholesterol was 194 mg/dl. Thirty-seven
      (24%) patients required further lipoprotein analysis based on cholesterol level,
      history of CHD and risk factors for CHD. Twenty-one (66%) of 32 patients who
      underwent lipoprotein analysis (14% of all patients) were candidates for a
      therapeutic intervention for hypercholesterolaemia. Additionally, 14 (44%)
      patients undergoing lipoprotein analysis had depressed high-density lipoprotein
      levels (< 35 mg/dl). We conclude that CHD risk factors including
      hypercholesterolaemia are common in Southeast Asian refugee clinic patients and
      that in many, a therapeutic intervention may well be justified. Southeast Asian
      refugees should be routinely screened for hypercholesterolaemia and other CHD
      risk factors in accordance with the National Cholesterol Education Program's
      guidelines.

PMID- 7650081
TI  - Stability and compatibility of anakinra with intravenous cimetidine hydrochloride
      or famotidine in 0.9% sodium chloride injection.
AB  - We designed a study to evaluate the stability and compatibility of anakinra
      (recombinant human interleukin-1 receptor antagonist) with cimetidine
      hydrochloride or famotidine in 0.9% sodium chloride injection during a 4-h period
      at room temperature (22 degrees C) and light. Anakinra was diluted in 0.9% sodium
      chloride to concentrations of 4 and 36 mg/ml. At each concentration, anakinra was
      mixed with 3 mg/ml cimetidine or with 1 mg/ml famotidine, in a 50:50 proportion
      and stored in plastic culture vials with polypropylene caps. The mean
      concentrations of anakinra, cimetidine hydrochloride, and famotidine exceeded 95%
      of initial concentrations throughout the study. No changes were noted in the
      physical appearance, pH, or the chromatograms during the study period. Thus,
      anakinra appears to be stable and compatible with cimetidine hydrochloride or
      famotidine when diluted into 0.9% sodium chloride injection for 4 h at ambient
      room temperature and light.

PMID- 7650080
TI  - Sleep quality and the use of benzodiazepine hypnotics in general practice.
AB  - The aim of the study was to determine the usage patterns of benzodiazepine
      hypnotics, the use of other ways of improving sleep and general sleep
      characteristics in patients prescribed these drugs on a regular basis and in a
      control group of age- and sex-matched patients not receiving hypnotics. Patients
      receiving regular benzodiazepine hypnotic prescriptions and a control group
      matched for age and sex were identified from a general practice computer. They
      were interviewed in their own homes about their habits relating to sleep,
      hypnotic use and attitudes to sleep and hypnotics. None of the recommended
      methods of improving sleep differed significantly in frequency between the two
      groups or had an effect on sleep parameters. Only daytime napping was found to be
      slightly more frequent in hypnotic users, but had no apparent effect on self
      estimates of sleep duration or latency. The hypnotic users claimed a longer sleep
      latency and a shorter sleep duration than non-users. More patients who took
      hypnotics also perceived them to be beneficial and more convenient than other
      ways of promoting sleep. The recommendation of sleep-promoting methods such as
      caffeine and alcohol avoidance and regular exercise may not be helpful in
      patients attempting to avoid hypnotics, as many patients already claim to use
      such methods.

PMID- 7650082
TI  - Recent studies of giftedness in children.

PMID- 7650083
TI  - Clinical implications of attachment concepts: retrospect and prospect.
AB  - The key features of attachment theory are summarized and the unresolved questions
      considered in terms of a behavioural control system, measurement of attachment
      security, qualities of attachment, the role of temperament, transformation of a
      dyadic quality into an individual characteristic, internal working models,
      manifestations of attachment post infancy, how one relationship affects another
      relationship, boundaries of attachment, associations with later functioning, the
      role of parenting qualities and patterns of caregiving, adaptive value of secure
      attachment, and disorders of attachment. The clinical implications are discussed
      in terms of: the need to reject the traditional psychoanalytic theories of
      development, the patterns of residential care for children, the provision of
      child care, the assessment of parenting, the effects of parental divorce and
      family break-up, "maternal bonding" to infants, psychotherapy and disorders of
      attachment.

PMID- 7650084
TI  - Mother-child interaction and the cognitive and behavioural development of four
      year-old children with poor growth.
AB  - A whole population inner-city survey identified 23 stunted, otherwise healthy,
      children with persistently poor growth from infancy to 4 years. Their cognitive
      development was significantly retarded relative to a matched comparison group.
      Unstructured home observations were used to create transcripts of verbal and
      nonverbal mother-child interactions. In both groups child behavioural adjustment
      was linked to maternal negativity, and cognitive performance was correlated with
      quality of stimulation. The developmental delay associated with chronic failure
      to thrive appeared more likely to arise from other influences, perhaps a previous
      biological insult, than to contemporaneous parenting practices.

PMID- 7650085
TI  - The adolescent outcomes of adoption: a 16-year longitudinal study.
AB  - The childhood history and adolescent adjustment of children placed in adoptive,
      biological two parent and single parent families were examined in a birth cohort
      of 1265 New Zealand children studied to the age of 16 years. This study suggested
      that children who entered adoptive families were advantaged throughout childhood
      in a number of areas including childhood experiences, standards of health care,
      family material conditions, family stability and mother/child interaction.
      However, the environmental advantages experienced by children who entered
      adoptive families were not directly reflected in the pattern of adolescent
      adjustment of this group. In particular, children placed in adoptive families had
      rates of externalising behaviours (including conduct disorders, juvenile
      offending and substance use behaviours) that were significantly higher than
      children reared in biological two parent families but somewhat lower than those
      of children who entered single parent families at birth.

PMID- 7650086
TI  - Extremity of externalizing behavior and young adult outcomes.
AB  - Data from the National Child Development Study were used to explore the
      relationship between extremity of externalizing behavior problems during
      childhood and employment-related outcomes in young adulthood. Analyses focused on
      four heuristic dimensions of extremity (age at onset, density, persistence, and
      pervasiveness) and three outcomes (school-leaving age, level of qualifications at
      labor force entry, and social class of job at age 23). Persistence was associated
      with the most substantial deficits across all outcomes, and temporal proximity
      was more influential than early onset. The data suggest that school-based and
      home-based situational behavior problems should not be combined into a single
      nonpervasive category.

PMID- 7650087
TI  - The orphans of Eritrea: a comparison study.
AB  - The social-emotional state and cognitive development was compared between a group
      of 74 4-7-year-old Eritrean orphans and refugee children living in families. Both
      groups had been exposed to the chronic stresses of war and drought, and the
      orphans had, in addition, lost both parents to the violence of war, and were
      living in an overcrowded orphanage. Contrary to expectations, there were
      relatively few clinically significant differences between comparison groups. The
      orphans showed more behavioral symptoms of emotional distress, but performed at a
      more advanced level on cognitive and language performance measures. The findings
      suggest that when group care is child-centered, it can under some circumstances
      be a viable solution for unaccompanied children in countries where adoption and
      foster care are not realistic alternatives.

PMID- 7650088
TI  - Psychometric properties of impulsivity measures: temporal stability, validity and
      factor structure.
AB  - Temporal stability, discriminant validity, and factor structure of an array of
      performance measures of impulsivity was assessed within samples of normal (N =
      48) and behaviorally disordered children (N = 88) ages 6-16 (126 M, 10 F; mean
      age = 10.57 years; SD = 2.13). Using a relatively conservative standard for
      adequate temporal stability, 31% of the variables derived from these measures met
      criterion. Of these, 83% were able to discriminate groups after partialling out
      the effects of intellectual aptitude and age. Factor analysis yielded a two
      factor solution interpreted as representing cognitive (inhibitory control) and
      motivational (insensitivity to punishment/nonreward) components of impulsivity.

PMID- 7650089
TI  - Adaptive skills dysfunction in ADD and ADHD children.
AB  - Adaptive functioning was examined in children with Attention Deficit
      Hyperactivity Disorder (ADHD) or Attention Deficit Disorder (ADD), and a
      psychiatric comparison group of children with pervasive developmental disorders
      or mild mental retardation (PDD/MR). As assessed with the Vineland Adaptive
      Behavior Scales, adaptive functioning was well below average for all three clinic
      groups. (The PDD/MR group had the lowest adaptive functioning scores, although
      not statistically different from the other groups). However, the level of
      adaptive functioning relative to IQ in the areas of Socialization, Communication
      and Daily Living was significantly lower for the ADD and ADHD groups. These
      deficits in adaptive functioning that characterize children with ADHD and ADD may
      help explain the poor long-term prognosis of ADHD, suggesting that increased
      attention should be paid to the assessment and treatment of adaptive functioning
      in individuals with ADHD and ADD.

PMID- 7650090
TI  - Self-control in boys with attention deficit hyperactivity disorder: effects of
      added stimulation and time.
AB  - Preference for larger-delayed versus more immediate-smaller rewards was studied
      in 5- and 6-year-old typical boys with Attention Deficit Hyperactivity Disorder
      (ADHD) in a repeated measure design. The effect of adding stimulation on
      preference also was studied. Boys with ADHD chose delayed-larger rewards
      significantly less than did typical boys. Adding stimulation reduced motoric
      behavior, but did not affect choice. As rates of motoric activity increased in
      boys with ADHD, their preference for delayed, larger rewards decreased over time.
      These findings argue for the external validity of choice tasks in the study of
      ADHD.

PMID- 7650091
TI  - An eight-year prospective study of older boys placed in permanent substitute
      families: a research note.
AB  - The psychosocial development of 16 boys placed in permanent substitute families
      between the ages of 5 and 9 was examined at 1, 12, 60 and 96 months into
      placement. Conduct and emotional problems fell significantly over the first year
      but relationship difficulties and overactivity changed little. There was no
      significant change beyond 12 months. By 8 years, 19% of placements had disrupted
      and 15% of the remainder had a poor outcome. The level of preplacement adversity
      predicted poor or disrupted outcomes, but outcomes for those with high adversity
      were better when parenting was very positive.

PMID- 7650092
TI  - Sustained attention, activation and MPH in ADHD: a research note.
AB  - Sustained attention was studied in children with attention deficit hyperactivity
      disorder (ADHD) and normal controls using a continuous performance task with slow
      presentation of stimuli and carried out with an experimenter-present and absent
      condition. Children with ADHD were slower than controls, with performance
      deteriorating over time, particularly in the experimenter-absent condition. Both
      the slowness and deterioration normalized when the children received MPH. Hence
      the rate of stimuli presentation and the presence or absence of experimenter are
      both crucial factors in the performance of children with ADHD. MPH is able to
      ameliorate the performance decrement seen under these conditions.

PMID- 7650093
TI  - Determination of sulfamethazine residue in chicken serum and egg by high
      performance liquid chromatography with chemiluminescence detection.
AB  - A sensitive method that involves high-performance liquid chromatography with
      chemiluminescence detection is developed for the determination of sulfamethazine
      residue in samples of chicken serum and egg. Sulfamethazine is extracted from the
      samples and derivatized with fluorescamine. The derivatized samples are eluted by
      reversed-phase chromatography using a mixture of 10 mM potassium phosphate and
      30% acetonitrile on a Nova-Pak C18 column. The post-column reagents in the
      chemiluminescence system are 1 mM bis[2-(3,6,9-trioxadecanyloxycarbonyl)-4
      nitrophenyl] oxalate and 0.3M hydrogen peroxide in acetonitrile. The detection
      limit in the standard solution is 1 ng/mL, and the calibration curve is linear
      between 1 and 100 ng/mL. The recoveries of spiked samples (50 ppb) are 95.8 +/-
      9.7% in chicken serum samples and 84.9 +/- 10.7% in egg samples. In actual sample
      analysis, the lowest detectable concentration of sulfamethazine (0.073
      microgram/mL) was found at 48 h in serum and on day 9 (0.017 microgram/g) in egg
      after oral administration of a dose of 100 mg/kg body weight to hens.

PMID- 7650094
TI  - Determination of propofol in blood by HPLC. Comparison of the extraction and
      precipitation methods.
AB  - The use of intravenous agents to maintain anesthesia has become increasingly
      popular since the introduction of propofol. Its popularity results from the fact
      that in 95% of patients given 2.5 mg propofol per kilogram of body weight, the
      induction of the drug is rapid and smooth and is followed by rapid recovery with
      a low incidence of postoperative side effects. In order to study the
      physiological effects of an intravenous anesthetic agent, it may be necessary to
      determine its concentration in blood. This paper deals with the high-performance
      liquid chromatographic analysis of propofol in blood. The concentration values
      are calculated from the application of extraction and precipitation procedures.
      Observed differences resulting from the two analytical methods are discussed and
      interpreted with reference to investigations of blood, plasma, and water
      solutions of propofol and the precipitation of solid elements in blood.

PMID- 7650095
TI  - GC-MS analysis of nonprotein amino acids in Gymnocladus dioicus as N(O,S)
      isobutyloxycarbonyl silyl derivatives.
AB  - Two different derivatives of novel nonprotein amino acids in Gymnocladus dioicus
      seeds are prepared for gas chromatographic (GC) and mass spectrometric (MS)
      analysis. The interfering components in a water extract of the seeds are removed
      by picric acid treatment and multistep washing with organic solvents followed by
      N(O,S)-isobutyloxycarbonylation combined with solid-phase extraction. The
      resulting N(O,S)-isobutyloxycarbonyl (isoBOC) amino acids are then converted to
      either tert-butyldimethylsilyl (TBDMS) or trimethylsilyl (TMS) derivatives, which
      are analyzed by dual capillary column GC and GC-MS. The characteristic ions in
      the mass spectra of N(O,S)-isoBOC TBDMS and N(O,S)-isoBOC TMS derivatives enable
      confirmation of molecular weight and existence of functional groups containing
      active protons. Temperature programmed retention index sets measured on DB-5 and
      DB-17 capillary columns (J&W Scientific; Folsom, CA) are useful for
      distinguishing among structural isomers. gamma-Methylglutamic acid,
      diastereoisomers of 3-hydroxy-4-methylglutamic acid, cis and trans isomers of 5
      hydroxypipecolic acid, and some free protein amino acids are identified in
      Gymnocladus dioicus seeds.

PMID- 7650096
TI  - Effects of sudden insight on long-term sentence priming in Alzheimer's disease.
AB  - The purpose of this study was to demonstrate spared, long-term sentence priming
      in individuals with Alzheimer's Disease (AD) using a sentence puzzle task. The
      sentence puzzle task required a decision--either yes or no--regarding the
      correctness of an answer supplied for a sentence puzzle. Twelve persons with AD,
      12 older controls, and 12 younger controls took part. Speed of response (deciding
      if a puzzle answer was correct or incorrect) was recorded, with increased speed
      at retesting after 30-min and 1-week delays used as an index of priming.
      Individuals with AD demonstrated sentence priming over both a 30-min and 1-week
      delay, comparable in form to that of controls. In addition, persons with AD were
      affected by stimulus parameters (correct/incorrect puzzle answers; difficult/easy
      puzzles) in a similar manner as were controls.

PMID- 7650097
TI  - Stroop color-word task as a measure of selective attention: efficiency in closed
      head-injured patients.
AB  - Deficits in attention and concentration are reported to be among the most common
      symptoms following head injury. Various underlying mechanisms of selective
      attention such as excitation, inhibition, and habituation have been isolated in
      recent studies. In the present study 27 control and 25 closed-head-injured (CHI)
      subjects were compared on four conditions based on the Stroop color-word task
      (neutral, habituation, Stroop, and negative priming). Cross-comparison of the
      different tasks enables examination of the various components of selective
      attention. The hypothesis that the control group's overall reading time would be
      faster than that of the CHI group was confirmed. Also confirmed was the
      hypothesis that the overall reading time pattern between task conditions would be
      neutral < habituation < Stroop < negative priming. The prediction that the CHI
      patients, due to their impaired inhibitory mechanism, would not show a slower
      reading time on the negative priming as compared to the Stroop condition, was
      confirmed as well. The theoretical and diagnostic implications of the results are
      discussed.

PMID- 7650098
TI  - Implicit memory in Alzheimer's disease.
AB  - While patients with Huntington's disease (HD) and Korsakoff's syndrome (KS)
      demonstrate "preserved" performance on implicit word-stem completion tasks,
      patients with Alzheimer's disease (AD) are typically found to be impaired. It has
      been hypothesized that AD patients do poorly as a result of degenerative changes
      in posterior cortical association areas thought to mediate performance on this
      type of implicit memory task, and that the relative sparing of these areas in KS
      and HD results in their "preserved" performance. The present study was undertaken
      to examine the implicit memory performance of AD patients on this task after
      equating their explicit performance to that of normal controls by manipulating
      the number of encoding exposures. When this was accomplished, the implicit memory
      performance of AD patients was equivalent to that of controls. The results are
      discussed within the context of a critical review of the evidence for the
      existence of separable neural systems in mediating implicit and explicit memory.

PMID- 7650099
TI  - Neuropsychological detection of dementia: an overview of the neuropsychological
      component of the Canadian Study of Health and Aging.
AB  - As part of the Canadian Study of Health and Aging (CSHA), a battery of
      neuropsychological measures was administered to 1879 participants. Participants
      who received neuropsychological evaluations were selected from an age-stratified
      random sample on the basis of scores on a cognitive screening tool, the Modified
      Mini-Mental State Examination (3MS). Seventy-five percent of the sample seen for
      neuropsychological evaluation scored between 50 and 77 on the 3MS and 25% of the
      sample scored 78 or over. This paper provides a descriptive summary of the
      methodological basis of the neuropsychological component of the CSHA. The
      findings indicated that differences existed between participants administered the
      battery in English or French in terms of refusal rates and diagnoses of dementia.
      Cursory examination of the utility of the battery indicated that the battery was
      tolerated well by both the participants and the psychologists involved with the
      study and that measures of memory functioning were central to diagnostic decision
      making. The relations between neuropsychological, preliminary medical and
      consensus diagnoses were examined and indicated that neuropsychological
      information influenced diagnostic decision-making. The neuropsychology component
      of the CSHA is a rich source of information on persons aged 65 years and older in
      Canada.

PMID- 7650100
TI  - Heterogeneity of cognitive profiles in normal aging: implications for early
      manifestations of Alzheimer's disease.
AB  - This study explores the presence of homogeneous subgroups among 156 normal
      elderly subjects based on their performance on a battery of neuropsychological
      tests. Subjects ranged in age between 57 and 85 years and included 62 males and
      94 females with a mean age 70.7 years, mean education 14.1 years, and mean Full
      Scale IQ of 117.2. Six clusters were extracted, three of which are likely to
      represent preclinical stages of the dementing process with distinct patterns of
      cognitive deficits. The results are discussed in light of different models of
      cognitive deterioration in DAT.

PMID- 7650101
TI  - Effectiveness of neglect rehabilitation in a randomized group study.
AB  - The effectiveness of neglect rehabilitation training has been studied in two
      randomly selected groups of right brain-damaged patients. All patients proved
      heminattentive on a standard battery 2 months or more after the CVA. One group
      received 2 months of treatment immediately after admission to a clinic, and the
      other group received only general cognitive stimulation for the same amount of
      time. At the end of this period a comparison showed significant improvement in
      the first group, based on a standard test battery and a functional scale. The
      second group was then given rehabilitation training for neglect for the same
      amount of time and obtained similar improvement. It is concluded that the
      rehabilitation program produces significant results, which generalize to
      situations similar to those of everyday life. The importance of the duration of
      training on the generalization of learning is briefly discussed with reference to
      previous negative reports in the literature.

PMID- 7650102
TI  - Color- and picture-word Stroop tests: performance changes in old age.
AB  - The Stroop test comes in different variations, but all of them index performance
      on a basic task, like color or picture naming, when it is carried out by itself
      versus when it is performed in the presence of conflicting or incongruent
      stimuli. The present study examined the hypothesis that Stroop interference--the
      cost of performing one task in the presence of another--is a general as opposed
      to a test-specific index of cognitive flexibility. A second goal was to examine
      changes in Stroop test performance in old age. A group of 129 healthy older
      adults (> or = 65 years of age) were assessed on the color- and picture-word
      Stroop test, as well as on a battery of neuropsychological tests. Subjects'
      performance on each card of both Stroop tests, and various derived (differences
      and ratios) scores, were used to prepare age-group norms. The use of the norms is
      illustrated with findings from previous studies. Regression analyses showed age
      changes in several aspects of Stroop test performance. Hierarchical multiple
      regression analyses, and causal modeling showed an age effect on Stroop
      interference only on the picture-word test but not on the color-word test.
      Exploratory factor analysis of the Stroop data and the neuropsychological test
      data revealed different factor loadings for the color- and picture-word test. The
      combined findings suggest that the color- and picture-word Stroop test measure
      different cognitive functions, at least in old age.

PMID- 7650103
TI  - Sustained attention training for unilateral neglect: theoretical and
      rehabilitation implications.
AB  - Many studies have shown a co-variation of unilateral neglect with nonlateralised
      attentional functions. Recently, Posner has argued that there are two separate
      neural systems that influence the posterior attentional system which is presumed
      to be impaired in unilateral neglect, namely, the posterior system itself
      (located partly in the inferior parietal lobules) as well as a secondary
      modulatory sustained attention or vigilance system. This latter system is linked
      to the nor-epinephrine system, which is known to be more strongly represented in
      the right compared to the left hemisphere of the brain. If this hypothesis is
      true, then unilateral neglect should be improved by increasing activation of the
      sustained attention system. Eight patients suffering from chronic left unilateral
      neglect were trained to sustain their attention by a self-alerting procedure
      partially derived from Meichenbaum's self-instructional methods. Using a multiple
      baseline-by-function design, as well as multiple-baseline-by-subject designs,
      statistically significant improvements in unilateral neglect as well in sustained
      attention were found following onset of sustained attention training, without
      corresponding improvements in control measures. Theoretical implications for the
      attentional underpinnings of unilateral neglect are discussed, as well as the
      rehabilitation implications of this training procedure.

PMID- 7650104
TI  - Do intracarotid barbiturate injections offer a way to investigate hemispheric
      models of anosognosia?
AB  - In a sample of 83 patients counterbalanced for side of temporal-lobe seizure
      focus, we examined unawareness of hemiplegia upon clearing of the deficit after
      bilateral sodium amobarbital injections. Unawareness occurred commonly (66%) and
      with equal frequency following left and right injections. These findings were not
      moderated by speech dominance, handedness, sex, or side of seizure focus.
      Unawareness occurred more frequently after injections contralateral to than
      ipsilateral to the major seizure focus and was related to objective memory
      performance after contralateral, but not after ipsilateral, injections.
      Unawareness of drug-induced hemiplegia was related to the functional status of
      the temporal lobe independently of hemispheric laterality or degree of frontal
      lobe inactivation as measured by filling of the anterior cerebral arteries.

PMID- 7650105
TI  - Taking account of age-related differences on Digit Symbol and Incidental Recall
      for diagnostic purposes.
AB  - The purpose of the present study was to develop age-related normative data on the
      WAIS Digit Symbol subtest, and a short form of the Digit Symbol Incidental Recall
      test, for a nonclinical population of English-speaking South Africans with a
      relatively high level of education. The tests were administered to 131
      individuals between the age of 20 and 89 years with at least 10 years of
      education (mean = 14.93 years; range = 10-22 years). A significant age effect was
      found on both tests. Preliminary normative data across five age groups (20-39, 40
      59, 60-69, 70-79, and 80-89 years) are presented, and are considered
      diagnostically useful for clinical practice on persons of above-average
      intelligence. The utility of the short form of the recall test is confirmed and
      advocated particularly for work on older age groups.

PMID- 7650106
TI  - Instability of cognitive asymmetry in Alzheimer's disease.
AB  - Patients with probable Alzheimer's disease (AD) were assessed
      neuropsychologically three times, at 6-month intervals, to identify those with
      patterns of performance suggesting hemispheric asymmetry in cerebral
      degeneration. By two different methods, over half of the patients satisfied
      liberal criteria for cognitive asymmetry on one or more assessments, but only 12
      15% did so on all three visits. This is the proportion expected by chance. The
      small, stable Low Verbal and Low Spatial groups did not differ from each other,
      nor from the globally impaired group, on clinical or demographic variables. The
      Low Spatial patients identified by either method had the earliest age of onset
      and had shorter durations of illness. Limited autopsy data suggest that AD
      patients with cognitive asymmetries are more likely to have brain pathology in
      addition to that typical of AD.

PMID- 7650107
TI  - Episodic and semantic memory in Alzheimer's disease and progressive supranuclear
      palsy: a comparative study.
AB  - We compared 13 patients with dementia of the Alzheimer's type (DAT) and 9
      progressive supranuclear palsy (PSP) patients, matched by age, sex, education,
      and the overall level of cognitive deterioration, measured by using the Dementia
      Rating Scale, and 12 normal controls. The results of this study confirm that the
      pattern of cognitive deterioration of PSP patients differs from that of DAT
      patients. While episodic memory is severely affected early in the course of DAT,
      it appears to be relatively spared in PSP. In contrast to previous suggestions,
      we found no evidence for differentially rapid forgetting in DAT, although we did
      confirm relatively preserved recognition memory in PSP. We had predicted that the
      performance of the DAT group on tests of semantic memory (the Boston Naming Test,
      the ADA Synonym Judgement Test, and the Pyramids and Palm Trees Test) would be
      worse than that of the PSP group. However, there was, in fact, no difference on
      any of these measures, except that the PSP patients showed a significantly
      greater deficit on the Synonym Judgement Test. We suggest that the underlying
      cause of the semantic memory impairment might, however, be different in the two
      pathologies.

PMID- 7650109
TI  - British Fertility Society annual conference. Liverpool, 10-12 May 1995.
      Abstracts.

PMID- 7650108
TI  - Caffeine influence on the motor steadiness battery in neuropsychological tests.
AB  - Caffeine is a widely used drug with various biological effects. The present
      investigation focuses on a possible influence of caffeine upon motor steadiness
      performance in tests routinely used in neuropsychological testing. Twenty-four
      healthy females between 23 and 38 years were investigated in a randomised double
      blind crossover study. A significantly poorer motor steadiness performance was
      found after ingestion of 300 mg of caffeine as compared to a placebo
      (decaffeinated coffee). Both error time and error count were increased after
      caffeine consumption. Caffeine also tended to reduce maze coordination test
      performance. We conclude that caffeine intake preferably should be avoided before
      neuropsychological testing of motor steadiness.

PMID- 7650110
TI  - Simultaneous DNA 'fingerprinting', diagnosis of sex and single-gene defect status
      from single cells.
AB  - Sex and cystic fibrosis status have been previously diagnosed separately at the
      single cell level. We have developed a sensitive, reliable, accurate and rapid
      (within 5-6 h) system for the simultaneous diagnosis of sex, cystic fibrosis and
      a DNA 'fingerprint' within a single reaction from a variety of single cells. As
      contamination cannot be totally excluded, particularly at the single cell level,
      DNA 'fingerprinting' can be used to assess the risk of contamination. High
      sensitivity with single cells is combined with very high specificity (estimated
      matching probability of 10(-7)-10(-8)), allowing the source of the amplified cell
      to be identified with a very high degree of probability. Fluorescent primers were
      multiplexed for six tetranucleotide microsatellite sequences to determine the DNA
      fingerprint; the amelogenin gene was used to diagnose sex, and primers for the
      CFTR region were used to determine cystic fibrosis (CF) status. Analysis of the
      fluorescent product was undertaken using an automated DNA sequencer with Genescan
      software. This technique has many applications such as prenatal and
      preimplantation diagnosis, forensic identification of small or degraded samples,
      and detection of contamination sources. DNA fingerprints of single haploid
      spermatozoa and other cells can be assessed, so ensuring the detection of both
      diploid and haploid contamination during preimplantation diagnosis.

PMID- 7650111
TI  - The use of first polar bodies for preimplantation diagnosis of aneuploidy.
AB  - A large proportion of patients undergoing in-vitro fertilization (IVF) are aged >
      or = 35 years. It has been estimated that in this age group, 50% of embryos are
      chromosomally abnormal, with aneuploidy being the major contributing factor.
      Since the origin of most aneuploidies is maternal meiosis I non-disjunction,
      unfertilized oocytes could be safely screened for aneuploidy by analysing their
      first polar bodies. To determine the feasibility of first polar body aneuploidy
      analysis, polar bodies were analyzed by fluorescence in-situ hybridization (FISH)
      using probes simultaneously for chromosomes X, Y, 18, 13/21 or X, Y, 18 and 16.
      Within 6 h of retrieval, 88% showed a normal segregation involving a single
      chromosome of each kind, with double-dotted hybridization signals, corresponding
      to dyads (chromosomes in metaphase I composed of two chromatids). The rest showed
      non-disjunction of full dyads (6%), or an unbalanced pre-division of dyads (6%),
      which gives a segregation of one chromatid or one dyad and a chromatid with the
      first polar body. But only 34% of polar bodies analysed 24 h after retrieval or
      later showed a normal segregation, with most of the other polar bodies showing
      balanced pre-division, with two separated hybridization signals for all the
      chromosomes analysed. The rates of non-disjunction and unbalanced pre-division
      after > or = 24 h in culture were similar to the rates in fresh oocytes. When
      both types of aneuploidy were considered together, an increase of aneuploidy with
      maternal age was detected, which although slight, was significant (P =
      0.025).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7650112
TI  - Immunology and reproductive medicine.

PMID- 7650113
TI  - Sperm retrieval methods and ICSI for obstructive azoospermia.

PMID- 7650114
TI  - Male birth rates are influenced by the insemination of unselected spermatozoa and
      not by clomiphene citrate.

PMID- 7650115
TI  - Sex selection--ethical issues.

PMID- 7650116
TI  - The current ethical controversy over reproductive medicine: prenatal diagnosis.

PMID- 7650117
TI  - The morality of prenatal diagnosis.

PMID- 7650118
TI  - Society must decide about prenatal diagnosis.

PMID- 7650119
TI  - A mathematical model of follicle dynamics in the human ovary.
AB  - A mathematical model has been developed to describe the rates of growth and death
      of follicles in human ovaries between 19 and 50 years of age. It was based on the
      numbers of follicles at three successive stages of development, which were
      obtained by counting follicles in histological sections of ovaries from 52 normal
      women. The model indicated that follicle dynamics were age dependent, with a
      transition at 38 years of age when the rate of follicle disappearance increased.
      The rates of follicle growth increased at successive stages but did not change
      with age. The annual egress from stage III (consisting of follicles with two or
      more granulosa cell layers) was affected by the declining numbers of small
      follicles, and corresponded to 31, nine and one follicles per day at 29-30, 39-40
      and 49-50 years of age respectively. The rate of death at stage I (representing
      small, resting follicles) was the only parameter which varied significantly with
      age: no evidence of significant atresia was found for this stage in ovaries < or
      = 38 years old, but there was significant death above this age. As a consequence,
      only 40% of follicles leaving stage I reached stage III in older ovaries and just
      1500 follicles in toto remained at 50 years of age from the 300,000 present at 19
      years. This high death rate of small follicles appears to be responsible for
      advancing the timing of ovarian failure, and therefore of menopause, to midlife
      in our species.

PMID- 7650120
TI  - Menstruation is associated with disordered expression of desmoplakin I/II and
      cadherin/catenins and conversion of F- to G-actin in endometrial epithelium.
AB  - Endometrium is unique since it is the only tissue that undergoes regular cyclic
      bleedings. Menstrual shedding is associated with the breakdown of endometrium,
      including the fragmentation of endometrial glands. To gain insight into the
      underlying basis of fragmentation of the endometrial epithelium during the
      menstrual phase, we examined the expression of proteins implicated in epithelial
      cell-cell binding in human endometria throughout the entire menstrual cycle.
      Western blotting failed to reveal differences in the relative amount of E
      cadherin, alpha- or beta-catenin or actin in the menstrual endometria compared
      with those in the proliferative or secretory phases. However, specific changes in
      the expression pattern of these proteins as well as desmoplakin I/II were
      detected by immunohistochemical staining in epithelial cells of menstrual
      endometria. Desmoplakin I/II, E-cadherin, alpha- and beta-catenins and beta-actin
      were localized to intercellular borders as well as the luminal and basal regions
      of glandular epithelium during the proliferative and secretory phases.
      Immunoreactivity of E-cadherin and alpha-catenin was confined to epithelial
      cells, whereas beta-catenin and beta-actin were present in epithelial cells, as
      well as in stroma and endothelial cells. Binding of F-actin to fluorescein
      isothiocyanate-labelled phalloidin localized this form of actin to the
      intercellular borders, and the basal and luminal cytoplasm of epithelial cells in
      proliferative and secretory endometria. Menstrual shedding was associated with
      disorganization of the site-specific distribution of desmoplakin I/II, E-cadherin
      and alpha- and beta-catenins.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7650121
TI  - Morphological characteristics of human endometrial epithelial cells cultured on
      rat-tail collagen matrix.
AB  - Epithelial cells were isolated from normal human endometrium and cultured on
      reconstituted matrices of rat-tail collagen gels. Cells attached within 24 h
      after plating. Initially, epithelial cells were not structurally polarized, had
      projections from both apical and basal domains and were generally flat to
      cuboidal in shape. When the gels were made free floating 36-48 h after initiation
      of the cultures, the epithelial cells became columnar in shape as the gels
      underwent contraction. Although a maintained growth profile was observed during
      the 10 days of culture, there was a linear decrease in gel matrix diameter along
      with increasing loss of transparency. Electron microscopy revealed the presence
      of apical microvilli, junctional complexes, lipid droplets and endoplasmic
      reticulum in cultured epithelial cells. The basolateral dilatations and lateral
      membrane plications were seen in these cells by 6-8 days in culture. With gel
      contraction, rearrangement of matrix material was observed. Occasionally there
      were basal lamina-like structures adjacent to the flattened basal surface and the
      formation of gland-like structures within the matrix. The three-dimensional
      primary culture of human epithelial cells on collagenous biomatrix appears to be
      a potential experimental tool for the study of cell-cell and cell-matrix
      interactions, and of the study of the effects of endocrine and paracrine factors
      on these cells in vitro.

PMID- 7650122
TI  - Prospective randomized study of clomiphene citrate and gonadotrophins versus
      goserelin and gonadotrophins for follicular stimulation in assisted reproduction.
AB  - We performed a prospective randomized study of goserelin, a long-acting
      gonadotrophin-releasing hormone agonist (GnRHa) and human menopausal
      gonadotrophin (HMG) versus clomiphene citrate and HMG for follicular stimulation
      in assisted reproduction to investigate whether the use of this GnRHa provides a
      clear advantage in terms of pregnancy per treatment cycle in unselected patients,
      who entered a first trial of assisted reproduction. From a retrospective analysis
      comparing the two stimulation protocols, a relative increase of the pregnancy
      rate per cycle of 50% was anticipated. To detect this difference with a power of
      90%, 300 patients had to be included. The main prognostic factors affecting the
      outcome of assisted reproduction were equally divided among the two groups by a
      minimization procedure. The pregnancy rates per cycle were significantly better
      in the goserelin/HMG group than in the clomiphene citrate/HMG group, both for all
      procedures of assisted reproduction combined (36.8 versus 24.5%; P < 0.02) and
      for the main procedure of in-vitro fertilization (IVF) (37.0 versus 23.5%; P <
      0.02). Differences in pregnancy rates per oocyte retrieval and per embryo
      transfer were less pronounced (37.8 versus 30.8%; P = 0.40 and 44.4 versus 36.8%;
      not significant). On the other hand, stimulation with goserelin/HMG was
      associated with a higher number of ampoules of HMG (44.9 versus 9.9; P < 0.0001),
      a longer duration of stimulation (11.2 versus 8.7 days; P < 0.0001) and an
      incidence of ovarian stimulation of 4.5% (7/154) versus 0% in the clomiphene
      citrate/HMG group. Goserelin was well tolerated and proved to be very reliable as
      an adjunct of follicular stimulation in assisted reproduction.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7650123
TI  - A comparison of two starting doses of human menopausal gonadotrophin for follicle
      stimulation in unselected patients for in-vitro fertilization.
AB  - Ovarian responses and embryology data were compared in patients undergoing in
      vitro fertilization following follicular stimulation using long course
      gonadotrophin-releasing hormone (GnRH) analogue/human menopausal gonadotrophin
      (HMG) in which the initial daily dose was two (150 IU) or three ampoules (225 IU)
      maintained for a minimum of 7 days. Group 1 (n = 31; centre A) patients were
      treated with a starting dose of two ampoules, while group 2 (n = 46; centre A)
      patients were treated chronologically immediately before group 1 with a starting
      dose of three ampoules per day. Group 3 (n = 74; centre B) patients were treated
      with three ampoules per day simultaneously with group 1. There was no difference
      in the distributions of patient ages or reasons for treatment between the three
      groups. Group 1 required longer treatment before the plasma oestradiol attained
      250 pg/ml than did both the other groups (group 1, 9.0; group 2, 6.9; group 3,
      6.7 days; P < 0.01), and this resulted in a longer follicular phase for group 1
      (mean: 14.5 days compared with 12.7 and 12.8 for groups 2 and 3 respectively; P <
      0.05). The numbers of follicles > 16 mm in diameter at human chorionic
      gonadotrophin (HCG) administration and the numbers of eggs and embryos were all
      significantly lower (P < 0.04) in group 1, and cycle cancellations due to
      insufficient ovarian responses were higher (P < 0.02) in group 1. There was no
      difference in the numbers of ampoules used, the oestradiol concentration at HCG,
      the fertilization and pregnancy rates or the incidence of hyperstimulation
      syndrome in the three groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7650124
TI  - Follicular fluid insulin-like growth factor-I and insulin-like growth factor-II
      concentrations vary as a function of day 3 serum follicle stimulating hormone.
AB  - We determined follicular fluid concentrations of insulin-like growth factor (IGF)
      I, IGF-II and inhibin as a function of day 3 serum follicle stimulating hormone
      (FSH) in 16 women undergoing follicular fluid aspiration in preparation for in
      vitro fertilization and embryo transfer. Follicular fluid concentrations of IGF-I
      and IGF-II were significantly less in the 'low' FSH group as compared to the
      'high' FSH group. The mean IGF-I concentration was 67.6 ng/ml [confidence
      intervals (CI) 51.6-92.5] in the 'low' FSH group compared to 87.1 ng/ml (CI 72.8
      104.2; P < 0.025) in the 'high' FSH group. Mean IGF-II concentrations were 354.8
      ng/ml (CI 297.8-422.9) in the 'low' FSH group compared to 489.8 ng/ml (CI 384.6
      624.5; P < 0.05) in the 'high' FSH group. Follicular fluid inhibin concentrations
      did not differ between groups. These differences in follicular fluid IGF as a
      function of day 3 FSH may raise questions regarding the role growth factors play
      in the physiological processes of the ageing follicle.

PMID- 7650125
TI  - Intravenous albumin does not prevent the development of severe ovarian
      hyperstimulation syndrome in an in-vitro fertilization programme.
AB  - A cohort study was undertaken to compare the effect at the time of oocyte
      retrieval of the i.v. administration of either 1000 ml of lactated Ringer's
      solution or 1000 ml of a 5% solution of human albumin on in-vitro fertilization
      patients at risk for severe ovarian hyperstimulation syndrome (OHSS). A total of
      207 patients with an oestradiol concentration > 10,000 pmol/l and/or > 15
      follicles (> 10 mm diameter) on the day of human chorionic gonadotrophin (HCG)
      injection were reviewed. Of these, 158 women received 500 ml of lactated Ringer's
      solution both before and after egg retrieval, and 49 women received two infusions
      of 500 ml of 5% human albumin in normal saline at the time of egg retrieval.
      Severe OHSS developed in two patients who received human albumin and in 10 women
      who did not receive the albumin. This difference was not statistically
      significant. There were no differences between the two groups in terms of age,
      number of follicles punctured at transvaginal oocyte retrieval or oestradiol
      concentration at the time of HCG injection. The administration of a 5% human
      albumin solution does not prevent the development of severe OHSS in at risk
      patients. It does appear to blunt the severity of the condition.

PMID- 7650126
TI  - Predictive value of serum oestradiol concentrations and oocyte number in severe
      ovarian hyperstimulation syndrome.
AB  - Ovarian hyperstimulation syndrome (OHSS) is a serious complication of
      gonadotrophin usage but it is difficult to accurately predict its occurrence.
      Previous investigators have identified the combination of high oestradiol
      concentrations and oocyte number as being predictive in 80% of cases. In this
      study we sought to identify the incidence of severe OHSS in patients with high
      oestradiol concentrations and large numbers of oocytes and to evaluate the
      importance of pregnancy in the development of OHSS. Between 1990 and 1993, we
      studied 139 cycles using two assisted reproductive techniques [oocyte donor, n =
      72; in-vitro fertilization (IVF), n = 67] in which either oestradiol (> 4000
      pg/ml), oocyte number (> 25), or both were elevated. OHSS was diagnosed by
      standard criteria. There were no cases of severe OHSS in the oocyte donor group
      and six in the IVF group. Among 10 patients with oestradiol concentration > 6000
      pg/ml and > 30 oocytes, only one had OHSS (10%). The relative risk of OHSS with
      pregnancy was 12 (confidence interval 2.18-66.14). We conclude that the risk of
      OHSS even at high levels of stimulation is lower than previously believed.
      Secondly, donors have a very low risk of OHSS, probably because of the absence of
      pregnancy. As such, cryopreservation of all oocytes in IVF cycles is a reasonable
      alternative to cycle cancellation or use of adjunctive medication.

PMID- 7650127
TI  - Mitogen-induced lymphocyte proliferation and peripheral blood mononuclear cell
      beta-endorphin concentrations in primary dysmenorrhoea.
AB  - Dysmenorrhoea is a recurrent painful disease which causes physical and
      psychological stress. The purpose of the present study was to investigate whether
      there was a measurable derangement of immune cells and immune responses in women
      with severe primary dysmenorrhoea. On day 26 of one cycle and on days 1 and 3 of
      the following cycle we measured polyclonal, mitogen-induced lymphocyte
      proliferation and beta-endorphin concentration in peripheral blood mononuclear
      cells obtained from 16 infertile women with normal pelvis, of whom eight had and
      eight did not have the disorder. In women with dysmenorrhoea, polyclonal mitogen
      induced lymphocyte proliferation was lower than in controls on all 3 days
      considered, but the difference was statistically significant only on day 26
      (43,605 +/- 9876 micrograms/ml versus 67,305 +/- 15,249 micrograms/ml; P < 0.01).
      Monocyte beta-endorphin concentrations in the patients with dysmenorrhoea were
      significantly elevated on day 3 compared to controls (67.8 +/- 24.3 pg/10(6)
      cells versus 29.7 +/- 6.9 pg/10(6) cells; P < 0.05). Our results demonstrate that
      immune responses are modified in patients with primary dysmenorrhoea. These
      effects are independent of circulating hormone concentrations and are consistent
      with the role of dysmenorrhoea as a stressful event.

PMID- 7650128
TI  - Genetic analysis prior to selective fetal reduction in multiple pregnancy:
      technical aspects and clinical outcome.
AB  - Multiple pregnancies resulting from ovarian stimulation are at a higher risk of
      carrying at least one fetus affected by Mendelian or chromosomal anomalies, the
      incidence of which is directly related to the order of multiples. Genetic
      analysis before fetal reduction was offered to both high- and low-risk pregnant
      women carrying two or more fetuses after ovulation induction. Chorionic villus
      sampling (CVS) and fetal reduction were achieved by transabdominal needling. The
      use of short-term culture, the polymerase chain reaction and fresh tissue
      enzymatic analyses have made it possible for genetic diagnosis to be available in
      a few days. A total of 100 patients had multifetal pregnancy reduction performed
      by a single operator; all of them completed pregnancy and none was lost at follow
      up. The total fetal loss before 24 weeks was 7% and no statistically significant
      relationship was found with the final number of fetuses and CVS. Perinatal losses
      (3.9%) were only present in the series with a final number of two fetuses.
      Pregnancy duration and birthweight were significantly higher in singletons than
      in twins, but were not related to CVS. The rate of chromosomal disorders was
      higher (7.2%) in the study series than in singleton pregnancies not undergoing
      fetal reduction. Diagnostic error due to incorrect sampling was reported in 1.5%
      of cases. These data support fetal reduction as a valuable strategy to improve
      the outcome of multiple pregnancy. The outcome of pregnancies reduced to
      singletons was significantly better than of those reduced to twins, and was not
      related to CVS.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7650129
TI  - Genetic basis of human reproductive endocrine disorders.
AB  - Disturbed human reproductive function may be caused by environmental and/or
      genetic factors. Much information related to single gene defects underlying
      reproductive failure has become available in recent years due to advances in
      molecular biology. In this review, techniques currently applied for
      deoxyribonucleic acid (DNA) analysis are addressed. We also highlight underlying
      molecular mechanisms and the corresponding clinical presentation of single gene
      defects affecting (i) the hypothalamic-pituitary-gonadal axis, resulting in
      disturbed gonadotrophin-releasing hormone (GnRH) neuron migration, or leading to
      defective gonadotrophins, gonadotrophin receptors and the Gs alpha protein; (ii)
      gonadal and adrenal steroid biosynthesis and (iii) steroid and insulin receptors.
      The potential genetic basis of polycystic ovary syndrome is also discussed.
      Although disease states caused by well-defined genetic abnormalities appear to
      represent only a small proportion of those found in the patient population, it
      should be considered that these affected individuals represent only the most
      severe cases in a wide spectrum of genetic abnormalities underlying disturbed
      fertility. Comprehension of these extreme cases will provide the basis for the
      elucidation of more common reproductive disorders as the result of subtle genetic
      changes or increased susceptibility to environmental factors.

PMID- 7650130
TI  - Transrectal electroejaculation in combination with in-vitro fertilization: an
      effective treatment of anejaculatory infertility after testicular cancer.
AB  - Treatment of non-seminomatous testicular cancer often leads to infertility due to
      anejaculation/retrograde ejaculation and poor sperm quality. In these men
      spermatozoa may be obtained by transrectal electroejaculation (TE), but the
      optimal strategy for assisted procreation in these couples is not known. Our aim
      was to examine whether TE and conventional in-vitro fertilization (IVF) would be
      successful. A total of 10 couples, with long-standing infertility due to
      anejaculation or retrograde ejaculation after treatment for testicular cancer 5
      14 years earlier, were referred to our unit. All men underwent diagnostic TE
      under general anaesthesia. Spermatozoa were recovered in nine cases. The
      antegrade fraction was prepared and used for IVF. Sperm quality was variable and
      conventional IVF was considered impossible in three cases. Altogether six IVF
      treatment cycles in six couples resulted in five pregnancies, of which four
      resulted in a delivery and one resulted in a spontaneous abortion. One additional
      pregnancy is ongoing after transfer of cryopreserved embryos. The fertilization
      rate was 54% (33/61) and the cleavage rate was 97% (32/33). No complications
      relating to the procedure have been encountered.

PMID- 7650131
TI  - The use of hemizona assay in the evaluation of the optimal sperm preparation
      technique.
AB  - The objective of the study was to evaluate the benefit of different sperm
      preparation methods by using the hemizona assay. A total of 58 men admitted to
      the male infertility clinic for evaluation were tested by routine semen analysis
      and hemizona assay. Five different techniques (swim-up, TEST-yolk buffer,
      Percoll, pentoxifylline and progesterone) were used for preparation of sperm
      suspensions. The effect of these treatments on the sperm-binding capacity using
      the hemizona assay was assessed. The routine swim-up preparation was used as the
      reference method. Of the four preparation methods, only the TEST-yolk buffer and
      pentoxifylline exhibited an overall statistically significant improvement in
      sperm-binding capacity in comparison with the swim-up preparation method (P =
      0.01 and 0.001 respectively). Following preparation with Percoll and progesterone
      there was no change in the mean value of binding capacity, compared with swim-up.
      However, examination of the effect of the four treatments on each specimen
      individually yielded a diversity in the response, e.g. having the capability to
      enhance, damage or be ineffective in sperm binding capacity. The results support
      the conclusion that in-vitro sperm preparation methods can affect sperm binding
      to the zona pellucida. Since there is a diversity in the response of sperm
      samples to different treatments, the hemizona assay can be used in selecting the
      optimal sperm preparation method prior to its use for assisted reproductive
      techniques. This is advocated mainly for the 'male factor' group.

PMID- 7650132
TI  - Application of different in-situ hybridization detection methods for human sperm
      analysis.
AB  - The detection of some types of aneuploidy in human spermatozoa can be based on
      the use of the fluorescence in-situ hybridization technique (FISH). One of the
      crucial steps for FISH is to achieve a proper decondensation and denaturation of
      the DNA in the specimen, so as to obtain efficient hybridization results.
      However, after DNA decondensation the morphology of sperm heads is partly
      distorted and the majority of the tails is lost. This situation leads to problems
      in the distinction between disomic and diploid spermatozoa, as well as between
      abnormal spermatozoa and somatic cells. Double- and triple-target FISH can partly
      solve this discrimination problem. To improve these procedures we adapted the
      steps of decondensation and visualization of the single sperm cells. Firstly, DNA
      decondensation with 25 mM dithiothreitol in 1 M Tris at pH 9.5 resulted in sperm
      cells with intact morphology of both the head and the tail, and allowed efficient
      single-, double- and triple-target ISH to be performed. Secondly, we applied a
      novel detection method, based on enzyme immunocytochemical reactions, with
      coloured precipitation products. Thirdly, this ISH procedure was combined with
      Diff-Quik staining and bright-field microscopy. This absorption method has the
      advantage of a permanent signal, and the adapted cytoplasmic staining of the
      sperm plasma membrane allows the visualization of the outline of the single
      spermatozoon. Using this approach, therefore, it is possible to discriminate
      between disomic, diploid and abnormal spermatozoa, somatic cells and spermatozoa
      that overlap, because the morphology of the cells is not distorted and the tails
      of the spermatozoa are intact and properly visualized.

PMID- 7650133
TI  - Tolerability of intramuscular injections of testosterone ester in oil vehicle.
AB  - We undertook a prospective survey of the tolerability of deep i.m. injections of
      testosterone enanthate in a castor oil vehicle, the most widely used form of
      androgen replacement therapy. Over a period of 8 months, 26 men received 551
      weekly injections into the gluteal, deltoid or thigh muscle and side-effects were
      recorded immediately and 1 week after each injection by the same nurse using a
      standardized questionnaire. Most injections caused no complaints [389/551, 70.6%
      (95% confidence interval 66.6-74.4%)] but minor local side-effects, mostly pain
      and bleeding, were common [162/551, 29.4% (25.6-33.4%)]; no serious side-effects
      were observed. Considering all side-effects, the gluteal site had fewer
      complaints and was less prone to bleeding but was painful more often than deltoid
      or thigh injection sites. The laterality of injection at any site had no
      significant effect on side-effects. The only systemic side-effect was episodes of
      sudden-onset, non-productive cough associated with faintness following eight
      injections [1.5% (0.6-2.9%)] which we speculate may have been due to pulmonary
      oil microembolism. We conclude  that, when administered by an experienced nurse,
      deep i.m. injection of testosterone enanthate in a castor oil vehicle is
      generally safe and well tolerated but causes relatively frequent minor side
      effects, including pain and bleeding. An improved depot form of testosterone
      would be highly desirable for androgen replacement therapy and hormonal male
      contraception.

PMID- 7650134
TI  - Hypotaurine in spermatozoa and genital secretions and its production by oviduct
      epithelial cells in vitro.
AB  - Taurine and/or hypotaurine are necessary compounds for sperm capacitation,
      fertilization and embryo development. Hypotaurine has a protective role against
      peroxidative damage. The object of this work was, on the one hand, to determine
      the precise amounts of hypotaurine and taurine in the sperm environment at the
      moment of fertilization, and on the other hand to evaluate the production of
      hypotaurine and taurine by oviduct epithelial cells. Hypotaurine and taurine were
      quantified in spermatozoa and seminal and tubal fluid of various species, and in
      secretions by oviduct epithelial cell layers in vitro. Significant amounts of
      taurine and hypotaurine were identified. Both compounds were quantified in pre
      ovulatory follicular fluid, i.e. in one of the fluids present at the site of
      fertilization. We also observed that hypotaurine and taurine are synthesized and
      secreted in vitro by oviduct epithelial cells. We were able to demonstrate that
      hypotaurine is stable when added to an in-vitro fertilization (IVF) culture
      medium. The effects of this compound should be more carefully studied in human
      IVF.

PMID- 7650135
TI  - Kinematics of capacitating human spermatozoa analysed at 60 Hz.
AB  - Hyperactivation is a concomitant of eutherian sperm capacitation, characterized
      by the development of high amplitude flagellar waves with a corresponding
      increase in velocity. In humans, kinematic values have been derived which
      describe the movement characteristics of spermatozoa analysed at 30 images/s.
      However, these values are frame rate-dependent, and modern computer-aided sperm
      analysis (CASA) instruments used for studying sperm movement now use 60 images/s.
      This study used first-principles manual track analysis to derive the range of
      movement characteristics which describe hyperactivated motility of human
      spermatozoa at 60 images/s. Standard terminology for centroid-derived movement
      characteristics, as recommended by the World Health Organization, was used. US
      standard (NTSC) video recordings of capacitating human sperm populations were
      replayed using a non-interlaced freeze-frame video cassette recorder, and
      individual tracks reconstructed on acetate overlays. Tracks were classified as
      either forward progressive or hyperactived based upon flagellar beating patterns,
      then reconstructed manually at x3540 and analysed using both manual methods and
      basic geometric calculations from (x, y) coordinates (Cartesian methods) similar
      to those used by CASA instruments. In all, 40 hyperactivated and 40 forward
      progressive tracks were studied. A set of Boolean arguments defining
      hyperactivated motility was derived, and there was generally good agreement
      between the limits derived by manual and Cartesian methods. The limits for the
      definition of hyperactivated motility of human spermatozoa at 60 Hz derived by
      Cartesian methods were: curvilinear velocity > or = to 180 micrograms/s and
      linearity < or = to 45% and wobble < 50% and amplitude of lateral head
      displacement ALHmean > 6.0 micrograms or ALHmax > 10.0 micrograms.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7650136
TI  - Pregnancy with spermatozoa from a globozoospermic man after intracytoplasmic
      sperm injection treatment.
AB  - We present a case of third trimester pregnancy occurring in a 29 year old woman
      after intracytoplasmic sperm injection (ICSI) treatment with spermatozoa from a
      globozoospermic man. We believe this is the first reported case. A 37 year old
      man was diagnosed with globozoospermia with normal sperm count and motility. In
      vitro fertilization and subzonal insemination treatments failed to achieve
      fertilization of any eggs. The ICSI method produced 50% fertilization, 75%
      cleavage rate and a singleton pregnancy with a female fetus. No pregnancy or
      fetal abnormalities have been noted after > 7 months of gestation.

PMID- 7650137
TI  - Combined effects of maternal age and delayed fertilization on the frequency of
      chromosome anomalies in mice.
AB  - Animal experiments indicate that both maternal age and delayed fertilization
      increase the incidence of chromosome errors in the offspring. In the present
      study, therefore, we examined how both factors act in combination. We set up
      normal (0 h delay) and delayed fertilization (6 h delay) subgroups in three
      different age groups (young, 3-4 months; middle-aged, 9-11 months; and old, 13-15
      months), and compared the incidence of chromosome anomalies and other
      reproductive effects among them. Although the present study confirmed two
      previous findings that aneuploidies increase with advancing maternal age, and
      that polyploidies increase with delayed fertilization in mice, it was not clear
      whether maternal age and delayed fertilization affected the occurrence of
      aneuploidies either additively or multiplicatively.

PMID- 7650138
TI  - Effects of granulosa cells and gonadotrophins on meiotic and developmental
      competence of oocytes in vitro in non-stimulated rhesus monkeys.
AB  - Specific aims of this study were to determine effects of granulosa cells and
      gonadotrophins on the meiotic and developmental competence in vitro of oocytes
      from non-stimulated rhesus monkeys. Oocytes (368) were obtained from small antral
      follicles (class 1: 700-999 microns; class 2: 1000-2500 microns) dissected from
      excised ovaries of 10 follicular and three luteal phase monkeys. Oocytes were
      cultured in one of four treatment groups: (i) granulosa cells (4 x 10(6) live
      cells/ml) + gonadotrophins (5 micrograms/ml follicle stimulating hormone and 10
      micrograms/ml luteinizing hormone), (ii) granulosa cells alone, (iii)
      gonadotrophins alone, or (iv) controls (no granulosa cells or gonadotrophins).
      Mature oocytes were inseminated and cultured until arrest of embryo development.
      Meiotic and developmental capacity was greater (P < or = 0.05) for oocytes from
      class 2 compared with class 1 follicles and from luteal compared with follicular
      phase monkeys. Culture of oocytes with gonadotrophins alone during in-vitro
      maturation improved (P < or = 0.01) activation and cleavage through the 5-8-cell
      stage (46.5%). Culture with granulosa cells alone during in-vitro maturation
      augmented progression of embryos to the morula stage (6.3%). The combination of
      granulosa cells+gonadotrophins enhanced (P < or = 0.01) nuclear maturation, but
      had no effects on developmental capacity beyond those of either treatment alone.
      In conclusion, both granulosa cells and gonadotrophins during in-vitro maturation
      have stimulatory effects on the meiotic and developmental competence of oocytes
      from non-stimulated macaques in vitro.

PMID- 7650139
TI  - Factors affecting activation and fertilization of human oocytes following
      intracytoplasmic injection.
AB  - Intracytoplasmic sperm injection (ICSI) has dramatically altered the treatment of
      severe male factor infertility, resulting in improved fertilization and pregnancy
      rates. The purpose of this study was to investigate oocyte activation and
      fertilization in aged human oocytes following ICSI. Non-viable spermatozoa were
      injected into 24 h old human oocytes in the presence and absence of calcium and
      were assessed for evidence of activation and fertilization 16-19 h after the
      injection procedure. Sham injections were also carried out to assess the effect
      of the injection procedure itself and the presence of calcium in the injection
      medium on oocyte activation. Non-viable spermatozoa injected in the presence of
      1.78 mM calcium were capable of normally fertilizing aged human oocytes and the
      resulting zygotes underwent cleavage. None of the oocytes injected with non
      viable spermatozoa in the absence of calcium were fertilized normally, although
      the rates of activation following all treatments were similar.

PMID- 7650140
TI  - Ongoing pregnancies and birth after intracytoplasmic sperm injection with frozen
      thawed epididymal spermatozoa.
AB  - In seven patients who did not become pregnant following microsurgical epididymal
      sperm aspiration (MESA) and intracytoplasmic sperm injection (ICSI), a subsequent
      ICSI was performed using previously cryopreserved super-numerary epididymal
      spermatozoa without re-operating on the husband. During the original MESA
      procedure a mean sperm concentration of 12.3 x 10(6)/ml was achieved. The
      supernumerary spermatozoa were cryopreserved for later use. After thawing frozen
      epididymal spermatozoa a mean concentration of 1.9 x 10(6) spermatozoa/ml was
      obtained in straws containing a total volume of sperm suspension of 250
      microliters. From 68 intact oocytes injected with frozen-thawed epididymal
      spermatozoa, a two pronuclear fertilization rate of 45% and a cleavage rate of
      82% were obtained. A total of 17 embryos were replaced in the seven patients,
      resulting in two ongoing singleton pregnancies and one twin delivery. Six embryos
      were cryopreserved. In conclusion, it would appear mandatory to cryopreserve
      supernumerary spermatozoa during a MESA in order to avoid subsequent further
      scrotal surgery.

PMID- 7650142
TI  - Leukaemia inhibitory factor in human endometrium during the menstrual cycle:
      cellular origin and action on production of glandular epithelial cell
      prostaglandin in vitro.
AB  - Leukaemia inhibitory factor (LIF) is a pleiotrophic cytokine which plays an
      obligatory role in mouse implantation. To investigate its potential role in the
      regulation of uterine function in the human, LIF secretion by isolated human
      endometrial glandular epithelial and stromal cells in primary culture was
      determined. Endometrial cells secreted a detectable amount of LIF protein during
      the first 48 h of culture. In the follicular and late-luteal phases, LIF
      secretion by both cell types was low. At every stage of the menstrual cycle, the
      epithelial cells secreted significantly more LIF than did stromal cells.
      Glandular epithelial cells of the mid-luteal phase, at the expected time of
      implantation in the human, secreted significantly more LIF than at other stages
      of the cycle. Stromal cells showed a similar, but nonsignificant, LIF secretion
      pattern. It could be concluded that endometrial LIF expression was dependent on
      cell type and stage of the menstrual cycle, and might thus play a role in human
      implantation. Oestradiol-17 beta stimulated both prostaglandin (PG) F and E
      release by the epithelial cells in both follicular and luteal phases. PGE release
      during the luteal phase was greater than in the follicular phase. However,
      addition of recombinant human LIF did not change either PGF or PGE release in
      either follicular or luteal phases, in the presence or absence of oestradiol.

PMID- 7650141
TI  - Uterine fluid human decidua-associated protein 200 and implantation after embryo
      transfer.
AB  - Uterine fluid samples from 109 patients undergoing in-vitro fertilization and
      embryo transfer were obtained so as to examine the relationship between the
      uterine fluid concentration of human decidua-associated protein (hDP) 200 and the
      implantation rate. The sampling was performed on the day of embryo transfer with
      a Wallace catheter, used for the testing of cervical patency before embryo
      replacement. The implantation rate, as well as the pregnancy rate, demonstrated a
      significantly positive correlation with the concentration of hDP 200 in the
      uterine fluid, measured just before embryo transfer. These results indicate that
      hDP 200, identified as a rheumatoid factor secreted by the endometrium, may be
      involved in the implantation process.

PMID- 7650143
TI  - Endometrial thickness appears to be a significant factor in embryo implantation
      in in-vitro fertilization.
AB  - To evaluate the role of endometrial thickness and pattern in in-vitro
      fertilization (IVF), these parameters were prospectively measured in 516 cycles
      of IVF with embryo transfer at our clinic. Pregnancy and embryo implantation
      rates were assessed for each mm of endometrial thickness and for each of three
      endometrial patterns. Embryo implantation, clinical and ongoing pregnancy rates
      were significantly higher in the patients with an endometrial thickness > 9 mm
      (24.4, 48.6 and 42.2% respectively) compared with those of < 9 mm (14.3, 16.0 and
      11.7% respectively; P < 0.005). Endometrial thickness was negatively influenced
      by age and positively influenced by oestradiol concentration. The majority of
      patients (69.8%) exhibited a 'ring' endometrial pattern. Embryo implantation and
      clinical pregnancy (statistically significant), as well as ongoing pregnancy
      rates (not statistically significant), were lower in patients exhibiting the
      'solid' pattern. Endometrial thickness is independent of pattern in its effect on
      pregnancy outcome. In conclusion, endometrial thickness > 9 mm as well as ring
      and intermediate endometrial patterns denoted a more favourable prognosis for
      pregnancy in IVF but thinner endometrium and those exhibiting a solid
      configuration had an acceptable pregnancy outcome.

PMID- 7650144
TI  - The bubble test: a new tool to improve the diagnosis of endometriosis.
AB  - The objective of this study was to determine the clinical sensitivity and
      specificity of a bubbling phenomenon, including peritoneal surfaces, as a
      diagnostic test for endometriosis during laparoscopy. A prospectively controlled
      study of women with infertility of at least 1 year duration, who underwent
      laparoscopy, was conducted at a medical school-affiliated private infertility
      centre and research foundation. The study included 48 prospectively enrolled
      female infertility patients who underwent laparoscopy. Of these, 32 were found to
      suffer from endometriosis (group A) and 16 control patients did not show any
      evidence of disease (group B). The study involved the irrigation of the posterior
      cul-de-sac with short bursts of either saline or lactated Ringer's solution,
      utilizing a standard laparoscopic aspiration/irrigation system, and the
      subsequent observation for an excessive soap-like bubbling phenomenon (positive
      bubble test) in association with endometriosis. All 32 endometriosis patients
      (group A) demonstrated a positive bubble test. In contrast, only two of the 16
      control patients (group B) were positive (P = 0.00242, Fisher's exact test; odds
      ratio, 8.000). A positive bubble test during laparoscopy was thus 100% sensitive
      and 88% specific for the diagnosis of endometriosis by laparoscopy, resulting in
      positive and negative predictive values of 94 and 100% respectively. Since the
      literature provides considerable evidence that the diagnosis of endometriosis
      during laparoscopy is frequently missed, a positive bubble test during
      laparoscopy therefore may be considered a reason to search further (possibly with
      biopsies) for endometriosis in the absence of obviously visible disease.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7650145
TI  - Use of a new CA 125 assay in the diagnosis of endometriosis.
AB  - Serum CA 125 concentrations are elevated in some women with endometriosis;
      however, the low sensitivity and specificity of the assay have made it
      impractical to use it as a diagnostic test for endometriosis. Recently a second
      generation CA 125 assay has been developed. The purpose of this study was to
      compare serum CA 125 concentrations in women with and without endometriosis using
      both the older assay and the new CA 125 assay and to determine if the new assay
      concentration improves the clinical utility of CA 125 in the diagnosis of
      endometriosis. A total of 123 patients with endometriosis, pelvic pain or
      infertility were enrolled. Blood for CA 125 was drawn in the cycle preceding
      laparoscopy or laparotomy, and concentrations found by the older and newer assays
      were correlated with the patients' endometriosis stage using the revised American
      Fertility Society classification of endometriosis. The CA 125 concentrations
      determined by the new assay were highly correlated with concentrations determined
      by the older assay in patients with and without endometriosis (r = 0.96). The
      sensitivity and specificity were slightly improved using the new CA 125 assay;
      however, this assay did not dramatically improve detection of endometriosis.

PMID- 7650146
TI  - Immunohistochemical study of c-erb B-2 protein expression in endometriosis.
AB  - Using immunohistochemical techniques, we studied the expression of c-erb B-2 in
      normal human endometrial tissue (n = 8), endometriosis interna (adenomyosis) (n =
      8) and endometriosis externa (endometriotic cyst of the ovary) (n = 6). The
      glandular epithelium of normal endometrial tissue specimens in the proliferative
      phase stained positively. Most of the cases of endometriosis studied showed no
      expression of c-erb B-2 in glandular epithelium. No expression was detected in
      either the normal or endometriotic stromal cells. Results suggest that c-erb B-2
      is not significantly involved in the pathogenesis of endometriosis.

PMID- 7650147
TI  - The relationship of endometriosis to endometrial sonographic studies prior to
      administration of human chorionic gonadotrophin in patients undergoing in-vitro
      fertilization and embryo transfer.
AB  - The objective of this prospective comparative study was to investigate the
      relationship of endometriosis to endometrial thickness and sonographic echo
      pattern prior to the administration of human chorionic gonadotrophin (HCG).
      Patients were matched by age and ovarian stimulation protocol. A total of 210
      patients undergoing in-vitro fertilization (IVF) and embryo transfer at a
      university-related IVF centre were enlisted. Of these, 105 women with
      laparoscopic confirmation of endometriosis were compared to an equal number of
      patients with laparoscopic confirmation of no endometriosis. Mean endometrial
      thickness did not differ between the groups (12.7 +/- 2.9 versus 12.2 +/- 2.5
      mm). The distribution of echo patterns was also the same, irrespective of
      diagnosis. Evaluation of clinical pregnancy rates showed no reduction in patients
      with endometriosis, regardless of stage, nor when comparing patients to controls.
      Endometriosis has no effect on the endometrial thickness or echo pattern measured
      by sonography prior to administration of HCG or the pregnancy rates following IVF
      and embryo transfer.

PMID- 7650148
TI  - Serum-soluble CD23 in patients with endometriosis and the effect of treatment
      with danazol and leuprolide acetate depot injection.
AB  - Activated B cells have recently been shown to produce soluble CD23 from their
      membranes. The serum-soluble CD23 concentration in 21 patients with pelvic pain
      diagnosed as having endometriosis and confirmed by histology, and in 18 patients
      without pelvic pain, who had a normal pelvis during laparoscopic sterilization,
      was studied by chemiluminescent enzyme-linked immunosorbent assay. The
      endometriosis patients were randomized to 3 months of either danazol or
      leuprolide acetate injection. Serum was taken before and after 3 months of
      therapy. The serum-soluble CD23 concentration was significantly elevated in
      patients with endometriosis when compared with the controls (P < 0.0001). There
      was no correlation between soluble CD23 concentrations and the severity of
      endometriosis (r = 0.48, P > 0.05). The serum concentration of soluble CD23
      decreased significantly on treatment with danazol but not leuprolide acetate (P <
      0.05). We conclude that the elevation of soluble CD23 in patients with
      endometriosis suggests that there is activation of B cells, which respond to
      danazol but not leuprolide acetate injection.

PMID- 7650149
TI  - Temporal relationship between the human chorionic gonadotrophin peak and the
      establishment of intervillous blood flow in early pregnancy.
AB  - The purpose of this study was to investigate the temporal relationship between
      the early pregnancy peak of circulating human chorionic gonadotrophin (HCG)
      concentration and the establishment of maternal blood flow in the placental
      intervillous space. The presence of blood flow echoes within intervillous space
      was determined by colour Doppler imaging from 44 women with clinically
      uncomplicated pregnancy between 6 and 18 weeks gestation. Circulating HCG, free
      alpha- and beta HCG subunits, oestradiol and progesterone concentrations were
      immunoassayed in blood samples collected at the time of Doppler examination. A
      continuous intervillous blood flow was detected in all cases with a gestational
      age > or = 11.7 weeks (n = 18) but never before this time. Circulating
      concentrations of free alpha HCG, oestradiol and progesterone were linearly or
      exponentially correlated with gestational age (r = 0.860, 0.903 and 0.538
      respectively, all with P < 0.001), indicating steady increase of these hormones
      with advancing gestation. However, the best fitted lines were found to be
      parabolic for HCG (r = 0.771, P < 0.001) and beta HCG (r = 0.695, P < 0.001),
      their highest points corresponding to 11.24 and 10.74 weeks gestational age
      respectively. The close temporal relationship between the Doppler advent of
      intervillous maternal blood flow and the HCG peak suggests that the establishment
      of the intervillous blood flow is associated with the decline in circulating HCG
      concentrations.

PMID- 7650150
TI  - A survey of semen donation: phase II--the view of the donors.
AB  - This report presents the findings of phase II of the survey of semen donation
      commissioned by the Human Fertilization and Embryology Authority (HFEA), the
      purpose of which was to obtain information about the motivations and attitudes of
      semen donors in comparison with a matched group of non-donors. A total of 14
      centres licensed by the HFEA to conduct donor insemination participated in the
      investigation. At each centre, all men who attended for their first or second
      appointment between 1st November 1993 and 31st January 1994 were asked to
      complete a questionnaire about the factors which prompted them to attend the
      centre and about their knowledge of, and attitudes towards, semen donation. In
      spite of the recommendation by the HFEA that attempts should be made to recruit
      as semen donors older men in stable relationships who already have children of
      their own and who wish to donate for altruistic reasons, it remains the case that
      the large majority of men in the UK who donate semen are young single students
      who are largely motivated by payment. Views on oocyte donation of women who had
      never donated oocytes were also obtained, and compared with views on semen
      donation of a matched group of men who had never donated semen.

PMID- 7650151
TI  - Review of the organized support network for infertility patients in licensed
      units in the UK.
AB  - In acknowledging that 'counselling is generally recognized as beneficial', the
      Human Fertilization and Embryology Authority (HFEA) Code of Practice requires
      that all infertility units provide counselling facilities to be available for
      patients. In this study, we intended to evaluate the support and counselling
      services made available by the licensed units in the UK. A questionnaire
      consisting of 30 questions was designed and sent to every licensed treatment unit
      in the UK. The data were coded on a nominal scale and, using a data entry
      program, loaded onto a computer. Using the Statistical Package for the Social
      Sciences program, a non-parametric frequency analysis was performed. Associations
      were examined with cross-tabulations and chi 2 analysis. A total of 62 units
      (61.4%) responded to the questionnaire, from both the private and National Health
      Service sectors. Of these, 95% have their own counsellor, most of whom (84%)
      practised on the premises. One-third of these counsellors had a dual role, mainly
      as nurses, social workers or in administration; 98.6% were trained in
      counselling, with only 28% having either the Certificate or Diploma in
      Counselling. One-third (32.2%) of centres charged for counselling, with only 13
      units indicating their charges. The majority of centres (78.8%) do not actively
      follow-up patients after counselling and one-quarter (25.5%) did not have a
      specific counselling room. Over two-thirds (68.4%) of centres described their
      support network as adequate. The results of this survey suggest that, although
      the requirements of the HFEA Code of Practice are being adhered to reasonably
      well, overall patient uptake of counselling is low.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7650152
TI  - Sperm donation in Israel.
AB  - Science and technology in the field of human reproduction present new legal,
      ethical and religious questions which do not always have immediate answers. The
      first step in the rapidly developed field of reproductive technology was the use
      of sperm donation (artificial insemination by donor, AID) and the establishment
      of sperm banks. The state of Israel faced these problems when the regulations for
      sperm donation were discussed. The fact that the main holy places for the three
      monotheistic religions are in Israel directly influences the make-up of the
      population constituents. Therefore, besides a majority of secular people, a high
      percentage of the population of Israel is very religious: Jews, Moslems and
      Christians. Thus any resolution relating to AID should take this demographic
      combination into account. The practice of AID is opposed by the different
      monotheistic religions. To avoid the conflict between secular and religious
      people, and between the different religions' perspectives, the legal problem of
      AID in Israel was solved not by laws but by regulations which were published by
      the Ministry of Health. The main idea behind this attitude is that the state and
      its authorities should not and do not deal with ethical or religious questions.
      Thus, the decision was left to the couples and to the donors. The regulations
      address technical requirements, health problems and confidential issues
      concerning the couple, the donor and the child. In this paper we present the
      different views relating to these problems as perceived by the different
      religions, and describe the solution that was accepted by the Israeli Ministry of
      Health.

PMID- 7650153
TI  - Social aspects of > 800 couples coming forward for gender selection of their
      children.
AB  - The social characteristics of 809 couples attending a sex preselection clinic
      have been studied. Their ethnic origins were: Indian 57.8%, European 32.0%,
      Chinese 3.6% and others 6.8%. The average number of boys and girls per family was
      0.09 and 2.70 respectively for couples wanting a boy, and 2.46 and 0.14 for those
      wanting a girl. The average age of the wives was 34.0 years. These figures were
      not significantly different in any ethnic subgroup. Out of all the couples, 80.6%
      stated that they would have had another baby even had sex preselection not been
      on offer; 37.5% of the couples interviewed have been treated so far. The figures
      among those treated are substantially the same as those for the whole group.
      Asian and Middle Eastern couples overwhelmingly wanted boys, whereas European
      couples showed a slight preference for girls. These results suggest that, given
      certain guidelines, sex selection is unlikely to lead to a serious distortion of
      the sex ratio in Britain and other Western societies, but may need careful
      monitoring in other parts of the world.

PMID- 7650154
TI  - The value of oestradiol estimations in controlled ovarian hyperstimulation
      cycles.

PMID- 7650155
TI  - The value of oestradiol estimations in controlled ovarian hyperstimulation
      cycles.

PMID- 7650156
TI  - Intracytoplasmic sperm injection of 1 day old oocytes after fertilization
      failure.

PMID- 7650157
TI  - Selection of 'antibody-free' spermatozoa from semen of patients with anti-sperm
      antibodies.

PMID- 7650158
TI  - Sexing human spermatozoa to control sex ratios at birth is now a reality.

PMID- 7650159
TI  - DNA-based X-enriched sperm separation as an adjunct to preimplantation genetic
      testing for the prevention of X-linked disease.
AB  - We report the world's first clinical pregnancy resulting from DNA-based
      enrichment for X-bearing human spermatozoa, for prevention of X-linked
      hydrocephalus. Sperm separation was followed by embryo biopsy and nested
      multiplex polymerase chain reaction (PCR) for gender determination. Enriched
      populations of X-bearing spermatozoa ranging from 80 to 89% pure as determined by
      fluorescence in-situ hybridization (FISH) resulted in in-vitro fertilization
      (IVF) rates indistinguishable from normal IVF procedures (65%). In two separate
      biopsy procedures, 7/9 and 15/16 of the resulting embryos were determined to be
      female by multiplex PCR. Embryo transfer resulted in a karyotypically normal
      female fetus. This technique should be widely applicable to gender selection for
      the prevention of genetic disorders.

PMID- 7650160
TI  - Immunohistochemical evidence of p53 protein in human placenta and choriocarcinoma
      cell lines.
AB  - We investigated the expression of the tumour-suppressor and cell cycle control
      protein p53 in human first trimester and term placenta, three choriocarcinoma
      cell lines (Jeg-3, JAR, BeWo) and human choriocarcinoma. Using monoclonal
      antibodies against p53 (DO-7, Ab-6, DO-1, PAb 1801), paraffin-embedded sections
      of first trimester and full-term placentae, human choriocarcinoma and Jeg-3, JAR
      and BeWo, as well as cytospins, were evaluated immunohistochemically. In
      addition, Western blots were carried out with the same antibodies on
      choriocarcinoma cell lines. In placentae, a small number of villous and
      extravillous cytotrophoblast cells, as well as very few syncytiotrophoblast
      cells, stained intensively. Also, p53 was visualized in some nuclei of the
      placental basal plate, whereas stroma and endothelium were negative for p53. Jeg
      3, JAR and BeWo also showed a positive nuclear reaction with all applied
      antibodies. In paraffin-embedded sections of human choriocarcinoma, staining was
      confined to the nuclei of malignant cells. The results suggest that p53 is
      overexpressed not only in malignant tumour cells but in certain trophoblast cell
      populations of the human placenta as well.

PMID- 7650161
TI  - The presence of platelet-derived endothelial cell growth factor in human
      endometrium and its characteristic expression during the menstrual cycle and
      early gestational period.
AB  - Decidualized tissues are characterized by the intensive outgrowth of the
      microvasculature. Several angiogenic factors are assumed to be involved during
      the drastic change in the vasculature occurring in the process of
      decidualization. We examined the possible role of platelet-derived endothelial
      cell growth factor (PD-ECGF), a known angiogenic factor, during the process of
      early decidualization in humans. The expression of PD-ECGF in human endometrium
      was demonstrated by Western blot analysis, a marked increase being found in
      decidualized endometrium. Immunohistochemical staining showed that PD-ECGF
      immunoreactivity was present mainly in decidualized endometrial stromal cells. We
      established a primary cell culture of human endometrial stromal cells which were
      differentiated into decidualized cells in vitro by the addition of progesterone.
      In this cell culture system, progesterone augmented the expression of PD-ECGF in
      a dose-dependent fashion. The addition of progesterone also resulted in an
      increased release of prolactin, a well-known marker for decidualization. These
      findings suggest that PD-ECGF may play a physiological role as a possible
      angiogenic factor in the process of decidualization of human endometrium.

PMID- 7650162
TI  - Tumour necrosis factor-alpha-mediated dyscohesion of epithelial cells is
      associated with disordered expression of cadherin/beta-catenin and disassembly of
      actin filaments.
AB  - Tumour necrosis factor (TNF)-alpha induced, in a time- and dose-dependent
      fashion, dyscohesion (cell-cell dissociation) of the endometrial epithelial
      cells. TNF-alpha impaired the ability of cells to aggregate and to attain
      compaction. The cell-cell adherent junction is a specialized region of the plasma
      membrane where cadherin molecules act as adhesion molecules and actin filaments
      are densely associated with the plasma membrane through a well-developed
      plasmalemmal undercoat. Dyscohesion induced by TNF-alpha was associated with the
      disordered expression of cadherin/beta-catenin at the sites of cell-cell contact.
      In addition, within the time-frame that dyscohesion was induced, TNF-alpha down
      regulated the expression of actin mRNA only at 100 ng/ml without modulating the
      overall amount of actin protein, its beta-isoform or the amount of ribosylated
      actin. However, TNF-alpha-mediated dyscohesion of epithelial cells was associated
      with loss of plasmalemmal undercoat as well as intracytoplasmic aggregates of F
      actin and a simultaneous increase in G-actin. The effect of cytochalasin-B, which
      disrupts actin filaments on cell-cell binding, was less pronounced than the
      effect of TNF-alpha, suggesting that the effect of this cytokine on dyscohesion
      is not solely dependent on the disassembly of actin filaments. These findings
      show that the induction of disordered expression of adhesion molecules, as well
      as disassembly of actin filaments, are implicated in the dyscohesion induced by
      TNF-alpha.

PMID- 7650163
TI  - Q-beta replicase-amplified assay for detection of Mycobacterium tuberculosis
      directly from clinical specimens.
AB  - We report the results of a study conducted to evaluate the performance of manual
      Q-Beta replicase-amplified Mycobacterium tuberculosis complex assay compared with
      that of culture for detecting M. tuberculosis directly from digested sputum
      pellets. A total of 261 specimens submitted to three tuberculosis testing
      laboratories were analyzed. Culture and acid-fast bacillus smear results were
      provided by the tuberculosis testing laboratories. Of these 261 specimens, 34
      (13% prevalence rate) were positive for M. tuberculosis by culture. The samples
      were digested and decontaminated by the testing laboratories by using their
      standard digestion and decontamination procedures. An aliquot of the digested and
      decontaminated pellet was sent to GENE-TRAK. The digested and decontaminated
      pellet was neutralized by washing it with 0.067 M phosphate buffer (pH 6.8), and
      the bacteria present in the washed pellet were heat inactivated at 100 degrees C
      for 15 min. The samples were combined with sample processing buffer containing
      GuSCN and were treated for 6 min in the GENE-TRAK Sample Processing Instrument to
      release the nucleic acids. The release rRNA was analyzed in a manual Q-Beta
      replicase assay format which incorporates elements of sandwich hybridization,
      reversible target capture, and Q-beta replicase signal amplification
      technologies. In comparison with culture, the overall assay sensitivity and
      specificity were 97.1 and 96.5%, respectively. The positive predictive value was
      80.5%, and the negative predictive value was 99.5%. After analysis of discrepant
      results, the assay sensitivity and specificity were 97.3 and 97.8, respectively,
      and the prevalence rate was 14%. The positive predictive value and the negative
      predictive value were 87.8 and 99.5%, respectively. The Q-Beta replicase assay is
      rapid sensitive, semiquantitative, and specific for the direct detection of M.
      tuberculosis from clinical specimens.

PMID- 7650164
TI  - Reverse transcription multiplex PCR for differentiation between polio- and
      enteroviruses from clinical and environmental samples.
AB  - For the rapid detection of polioviruses and their differentiation from
      nonpoliovirus enteroviruses, we developed a protocol in which clinical or
      environmental specimens are first inoculated onto cell cultures in tubes. After
      overnight incubation, the cultures are subjected to reverse transcription
      multiplex PCR with a primer pair which detects all enteroviruses (T. Hyypia, P.
      Auvinen, and M. Maaronen, J. Gen. Virol. 70:3261-3268 1989) and two newly
      designed primer pairs specific for all 36 poliovirus strains tested. The PCR
      products can unequivocally be identified by their lengths in agarose gels,
      whereas the genetic heterogeneity of the poliovirus strains precludes
      identification by back-hybridization with internal probes. The proposed protocol
      is highly insensitive to the inhibitory effects of substances in the sample
      (stool, sewage). It allows for the detection of polioviruses and for polioviruses
      to be distinguished from nonpoliovirus enteroviruses within 24 h, and it allows
      for the concomitant isolation of a viable strain suitable for further typing.

PMID- 7650166
TI  - Expression, self-assembly, and antigenicity of a snow mountain agent-like
      calicivirus capsid protein.
AB  - Virus-like particles were produced in insect cells infected with a recombinant
      baculovirus containing the capsid gene of MX virus, a Mexican strain of human
      calicivirus. These recombinant MX (rMX) particles were morphologically similar to
      recombinant Norwalk virus (rNV) particles as observed under an electron
      microscope and contained a single capsid protein with a molecular weight of
      57,000, which was slightly smaller than that of rNV. This protein was
      immunoprecipitated by sera from volunteers infected with the Snow Mountain agent,
      but it reacted weakly with sera from volunteers infected with NV. This protein
      did not react with hyperimmune antisera from animals immunized with rNV in the
      rNV antigen enzyme immunoassay (EIA). Seroresponses were detected from volunteers
      infected with Snow Mountain agent and Hawaii agent when the rMX particles were
      used as antigen in an EIA. This EIA also detected an immune response in the sera
      of child from whom the MX virus was isolated, and a high prevalence of antibody
      to MX virus was found in the sera of a cohort of Mexican children.

PMID- 7650165
TI  - Parent-to-child transmission is relatively common in the spread of the human
      polyomavirus JC virus.
AB  - JC polyomavirus (JCV), the causative agent of progressive multifocal
      leukoencephalopathy, is ubiquitous in the human population, infecting children
      asymptomatically and then persisting in renal tissue. In most adults, renal JCV
      replicates and the progeny are excreted in urine. We used this urinary JCV to
      elucidate the routes of JCV transmission. A 610-bp JCV DNA region (IG region)
      encompassing the 3'-terminal sequences of both T-antigen and VP1 (major capsid
      protein) genes was amplified by means of PCR from urine specimens collected from
      all members of seven families. JCV strains were then unequivocally identified by
      the nucleotide sequences of the amplified IG regions. We could identify 18
      distinctive JCV strains from 27 individuals. Different JCV strains were detected
      from all unrelated persons. However, the same viral strain was detected from one
      (four families), two (one family), or three offspring (one family) as well as
      from the fathers (three families) or from the mothers (three families). In total,
      the JCV strains detected in half of the JCV-positive children were identified in
      their parents. Since most humans are infected during childhood, these findings
      indicated that JCV is transmitted frequently from parents to children. We roughly
      estimated that 50% of JCV transmission occurs by this route and that the other
      50% occurs outside the family.

PMID- 7650167
TI  - High specificity of Trypanosoma cruzi epimastigote ribonucleoprotein as antigen
      in serodiagnosis of Chagas' disease.
AB  - We assessed the performance of an enzyme-linked immunosorbent assay (ELISA) with
      the Trypanosoma cruzi epimastigote ribosomal fraction (Tulahuen and Y strains) in
      order to improve the diagnostic specificity of the test. A total of 100 serum
      samples from patients with chronic Chagas' disease from Brazil and Argentina were
      studied. Sera from 116 patients, without Chagas' disease, including 10 with
      active mucocutaneous leishmaniasis and 20 with visceral leishmaniasis, were used
      as controls. Immunoglobulin G (IgG) antibodies against the ribosomal fraction
      (ribonucleoproteins [RNPs]) in the ELISA were found in 97% of samples from
      patients with Chagas' disease. A total of 99% of the sera from patients without
      the disease were negative, including sera from patients with mucocutaneous and
      visceral leishmaniases. The distribution of IgG isotypes in randomly chosen serum
      samples was determined by ELISA; IgG1 and IgG3 were predominant (100% exhibited
      IgG1 and 85% exhibited IgG3, and 50% also presented the IgG2 isotype. The
      distribution of the IgG subclasses was confirmed by the Western blot (immunoblot)
      technique. When total IgG was assayed by Western blot assay, no correlation was
      found between the pattern of serum reactivity and the clinical features of the
      patients with Chagas' disease. Therefore, no typical profile of polypeptide
      recognition could be associated with any clinical form of Chagas' disease
      (cardiomyopathy or megaviscera). Our results showed that sera from patients with
      Chagas' disease react with ribosomal antigens and display a typical profile of
      IgG isotypes (IgG1 plus IgG3). The RNP ELISA seems to have improved specificity
      compared with those of routine techniques such as the indirect immunofluorescence
      assay and hemagglutination because it better discriminates between patients with
      Chagas' disease and patients without the disease. Since sera from patients with
      leishmaniasis failed to show cross-reactivity with this antigen, the ELISA seems
      useful for detecting Chagas' disease as well as confirming the nature of sera,
      when it is doubtful whether the patients has Chagas' disease, by the isotype
      distribution of IgG.

PMID- 7650168
TI  - Comparison of four DNA-based methods for strain delineation of Candida
      lusitaniae.
AB  - Four methods for the accurate delineation of epidemiologically related and
      unrelated strains of Candida lusitaniae were compared. Three pulsed-field
      electrophoretic methods, including two contour-clamped homogeneous field gel
      electrophoresis methods (EKP-1 and EKP-2) yielding electrophoretic karyotype
      patterns of intact chromosomal DNA and a method in which the chromosomal DNA was
      macrodigested with the endonuclease SfiI prior to pulsed-field electrophoresis
      (MDP), and a random amplified polymorphic DNA (RAPD) assay were evaluated. A
      selected panel of 21 well-characterized isolated representing 13 strains of C.
      lusitaniae, including 7 epidemiologically related isolates of one strain (group I
      A), 3 epidemiologically related isolates of another strain (group I-B), and 11
      epidemiologically unrelated isolates (group II), were tested. All isolates were
      coded and tested in a blinded manner. All seven group I-A isolates were confirmed
      to be a single strain by the EKP-1 and MDP methods, and the three group I-B
      isolates were shown to be a single strain by the EKP-1, EKP-2, MDP, and RAPD
      methods. Subtle differences were noted with two of the group I-A isolates by the
      EKP-2 method, whereas three of these isolates were different by the RAPD method.
      Each group II isolate had distinct patterns by all four methods. These data
      support the fact that the three pulsed-field electrophoretic methods and the RAPD
      method can be used to delineate strains of C. lusitaniae. The EKP-1, EKP-2, and
      MDP gave results that correlated with the epidemiologic characteristics of the
      isolates tested in the study, whereas the RAPD method was perhaps too sensitive
      in detecting DNA changes for epidemiologic studies.

PMID- 7650169
TI  - Multiple strains of Streptococcus pyogenes in skin sores of aboriginal
      Australians.
AB  - A molecular technique (random amplification of polymorphic DNA) was used to
      characterize group A streptococcal (GAS) strains among 194 isolates from 55 swabs
      from 12 Australian Aboriginal children and adults with multiple pyoderma lesions.
      Ninety-three percent of the lesions contained only one strain of GAS, but 8 of 12
      individuals were infected with more than one strain. We conclude that accurate
      epidemiologic surveys require that more than one swab specimen be obtained from
      each person, whereas typing of more than one colony per swab is less informative.
      Characterization of GAS strains by random amplification of polymorphic DNA
      analysis should help to provide important insights into the epidemiology of GAS,
      particularly in tropical populations where many isolates are M nontypeable, and
      into the mechanisms of genetic variation of GAS in such populations.

PMID- 7650170
TI  - Variable serum immunoglobulin responses against different Borrelia burgdorferi
      sensu lato species in a population at risk for and patients with Lyme disease.
AB  - Borrelia burgdorferi sensu lato species display considerable antigenic
      polymorphism. In order to evaluate the importance of this antigenic heterogeneity
      in the serodiagnosis of Lyme disease, the serum immunoglobulin G response in 148
      healthy individuals from an area in northern Sweden where Lyme disease is endemic
      and in 40 American patients with Lyme disease was assessed. In a seroprevalence
      study, the control group included 173 individuals from a region of northern
      Sweden where Lyme disease is not endemic. The two enzyme immunoassays used were
      based on outer membrane-associated proteins of either B. burgdorferi sensu
      stricto or Borrelia garinii. The Swedish populations were also screened for
      antiflagellum seroreactivity. The individuals from the area of endemicity were
      significantly more seropositive for the subcellular protein fraction of the local
      B. garinii isolate NBS16 than the control group (11.5 versus 2.9%; P = 0.005) but
      were not significantly more positive for the other antigens used. In contrast,
      American patients with Lyme disease were significantly more reactive against the
      North American B. burgdorferi sensu stricto strain B31 than against B. garinii
      NBS16 (57.5 versus 15.0%; P = 0.0001). Immunoblot analysis suggests that the
      borrelial outer surface protein C is involved in triggering the production of
      species-specific antibody during localized Lyme disease. We conclude that a
      species-specific immune response develops during infection with Lyme disease
      Borrelia spp. Thus, the reliability of a serological investigation of Lyme
      disease increases when one measures antibody titers against the outer membrane
      proteins of Lyme disease Borrelia spp. occurring in a particular geographic
      region.

PMID- 7650171
TI  - Diagnosis of congenital toxoplasmosis by immunoblotting and relationship with
      other methods.
AB  - Immunoblot has been evaluated as a diagnostic method for congenital
      toxoplasmosis. Like enzyme-linked immunofiltration assay (ELIFA), immunoblot can
      be used to compare antibody patterns and to determine if the antibodies are
      transmitted by the mother or synthesized by the fetus or infant. Among the 48
      infants tested, 27 had congenital toxoplasmosis and 21 were suspected but had
      none. Reproducibility, sensitivity, specificity, and positive predictive values
      in immunoblot for immunoglobulins (Igs) G+M+A and/or G+M were 90, 92.6, 89.1, and
      92.4%, respectively. G+M immunoblot and G+M ELIFA have better sensitivities than
      the conventional IgM immunosorbent agglutination assay, IgM enzyme-linked
      immunosorbent assay (ELISA), IgM immunofluorescence antibody test, in vitro
      culture, and mouse inoculation. The novel antibodies, i.e., those synthesized by
      infants against Toxoplasma gondii, were of the IgG class in most cases, although
      a confident diagnosis could be related to the number of observed Ig classes (G+M,
      G+A, and G+M+A). Immunoblot has a better resolution than ELIFA. In prenatal
      diagnosis, immunoblot could be complementary to in vitro culture and mouse
      inoculation. In the other cases, early detection by immunoblot appears to give
      the best results when compared with the other serological methods.

PMID- 7650172
TI  - Rapid bacterial antigen detection is not clinically useful.
AB  - Latex agglutination (LA) of capsular polysaccharide bacterial antigen is a
      frequently performed laboratory procedure, but its use is controversial. To
      assess the clinical utility of this test, we reviewed all LA tests performed over
      a 10-month period at two sites, a major university-based referral center and a
      private specialty pediatric hospital. Samples were assayed either individually or
      as a panel for the group B streptococcus, Streptococcus pneumoniae, Haemophilus
      influenzae, and three sets of Neisseria meningitidis serogroups (A and Y, C and
      W135, and B and Escherichia coli K1). Of 5,169 assays performed on 1,268 clinical
      samples (786 urine and 478 cerebrospinal fluid, 3 pleural fluid, and 1 synovial
      fluid sample), 57 (1.1%) were positive, including 1.7% of urine and 0.3% of
      cerebrospinal fluid samples. All LA true-positive cerebrospinal fluid samples
      showed the causative microorganisms by Gram stain. Detailed chart review of these
      57 positive samples showed that the LA result was false-positive in 31 (54%),
      true-positive in 22 (38%), and indeterminate in 4 (7%) samples. Therapy was not
      altered on the basis of any of the true-positive LA results. The 31 false
      positive results led to additional cost, prolonged hospitalization, and some
      clinical complications. Total patient charges were $175,000 ($7,954 per true
      positive), with no detectable clinical benefit. Our retrospective study does not
      support the current use of LA for rapid antigen detection. What, if any, specific
      indications exist for this test remain to be elucidated.

PMID- 7650173
TI  - Seroepizootiology of Helicobacter pylori gastric infection in nonhuman primates
      housed in social environments.
AB  - We determined the seroepizootiology of Helicobacter pylori infection in rhesus
      monkeys. Plasma was obtained from 196 animals (age range, 1 to 22 years) that
      were housed in social environments, either in indoor gang cages, in outdoor
      corrals, or in free-ranging forested conditions. Plasma immunoglobulin G levels
      were determined with a specific enzyme-linked immunosorbent assay, and the cutoff
      immunoglobulin G value for H. pylori seropositivity was determined from a study
      of 25 monkeys whose infection status was assessed by light microscopy and
      culture. One-year-old animals of both genders in all housing conditions had the
      lowest rate of positivity (60% in monkeys 1 year old versus 81% in monkeys 2 to
      10 years old, P = 0.026). In addition, females tended to have higher rates of
      positivity than males. Seroconversion during a 1-year observation period occurred
      in 7 (28%) of 25 seronegative animals. Seroreversion occurred in 3 (4%) of the 78
      positive animals; all 3 of these animals had received antimicrobial agents during
      the year. These observations demonstrate that the epizootiology of H. pylori
      infection in rhesus monkeys may serve as a model for human infection.

PMID- 7650174
TI  - Serologic detection of infection with cagA+ Helicobacter pylori strains.
AB  - Approximately 60% of Helicobacter pylori isolates possess the cagA gene and
      express its 120- to 140-kDa product (CagA). In this study, the cagA gene was
      detected in H. pylori isolates from 26 (81.3%) of 32 patients with duodenal
      ulcers (DU), 17 (68.0%) of 25 patients with gastric ulcers, and 23 (59.0%) of 39
      patients with nonulcer dyspepsia (NUD). By Western blotting (immunoblotting) with
      antiserum to CagA, in vitro CagA expression was demonstrated for 95.5% of cagA+
      strains compared with 0% of strains lacking cagA. Sera from patients infected
      with cagA+ strains (n = 66) reacted with recombinant CagA in an enzyme-linked
      immunosorbent assay to a significantly greater extent than either sera from
      patients infected with strains lacking cagA (n = 30) or sera from uninfected
      persons (n = 25) (P < 0.001). A strain lacking cagA was isolated from eight
      patients who had serum immunoglobulin G antibodies to CagA, which suggests that
      these patients were infected with multiple strains. Serum immunoglobulin G
      antibodies to CagA were present in 87.5, 76.0, and 56.4% of patients with DU,
      gastric ulcers, and NUD, respectively (odds ratio, 5.41; 95% confidence interval,
      1.44 to 24.72; P = 0.004 [DU versus NUD]). These data demonstrate an association
      between infection with cagA+ H. pylori and the presence of duodenal ulceration
      and indicate that serologic testing is a sensitive method for detecting infection
      with cagA+ strains.

PMID- 7650175
TI  - Colonizing populations of Candida albicans are clonal in origin but undergo
      microevolution through C1 fragment reorganization as demonstrated by DNA
      fingerprinting and C1 sequencing.
AB  - The genetic homogeneity of nine commensal and infecting populations of Candida
      albicans has been assessed by fingerprinting multiple isolates from each
      population by Southern blot hybridization first with the Ca3 probe and then with
      the 0.98-kb C1 fragment of the Ca3 probe. The isolates from each population were
      highly related, demonstrating the clonal origin of each population, but each
      population contained minor variants, demonstrating microevolution. Variation in
      each case was limited to bands of the Ca3 fingerprint pattern which hybridized
      with the 0.98-kb C1 fragment. The C1 fragment was therefore sequenced and
      demonstrated to contain an RPS repetitive element. The C1 fragment also contained
      part or all of a true end of the RPS element. These results, therefore,
      demonstrate that most colonizing C. albicans populations in nonimmuno-suppressed
      patients are clonal, that microevolution can be detected in every colonizing
      population by C1 hybridization, and that C1 contains the repeat RPS element.

PMID- 7650176
TI  - Inhibitory activity in saliva of cell-to-cell transmission of human T-cell
      lymphotropic virus type 1 in vitro: evaluation of saliva as an alternative source
      of transmission.
AB  - Human T-cell lymphotropic virus type 1 (HTLV-1) is known to be transmitted
      vertically through breastfeeding and horizontally by blood transfusion and sexual
      contact. Our intervention study has suggested the presence of additional
      alternative maternal transmission pathways. To explore the possibility of
      transmission through saliva, we used PCR to quantify the HTLV-1 provirus in
      saliva samples from 18 carrier mothers and 10 patients with HTLV-1-associated
      myelopathy/tropical spastic paraparesis. The provirus was detected in 60 and 90%,
      respectively, of the samples, with estimated copy numbers in the range of 10 to
      10(4)/ml. However, the saliva, regardless of the presence or absence of
      antibodies to the virus, showed a strong tendency to inhibit the cell-to-cell
      transmission of HTLV-1 in vitro, as examined by a syncytium inhibition assay. The
      natural inhibitory activity in saliva of seronegative volunteers was heat
      sensitive, and most of the activity was recovered by ultrafiltration in the
      fraction of macromolecules with a molecular weight of more than 100,000. In
      addition to this natural activity, saliva of HTLV-1-infected individuals
      contained immunoglobulin G molecules capable of neutralizing syncytium formation.
      These results strongly suggested that HTLV-1-infected cells in the carriers'
      saliva, which contains neutralizing antibodies in addition to the natural
      activity inhibiting cell-to-cell viral infection, barely transmit the virus.
      Transmission of HTLV-1 through the saliva would thus seem to be rare, if it
      occurs at all.

PMID- 7650177
TI  - Geographic distribution of human rotavirus VP4 genotypes and VP7 serotypes in
      five South African regions.
AB  - The rotavirus outer capsid proteins elicit the production of neutralizing
      antibodies and are known to play a role in inducing resistance to disease. In
      this study, cDNA probes directed at the six most common human rotavirus VP7
      serotypes (G1 to G4, G8, and G9) and five human rotavirus VP4 genotypes (P4, P6,
      P8, P9, and P10) were utilized. Hybridization analysis of 572 human rotavirus
      strains collected from five regions in South Africa was performed to determine
      the distribution of the VP7 serotypes and VP4 genotypes in nature. VP7 serotype
      G1 was identified most frequently, occurring in 51% of the rotavirus strains
      tested. VP7 serotypes G2 and G4 occurred in similar numbers, although their
      distribution varied regionally. Few serotype G3 strains and no G8 or G9 strains
      were identified. The P8 VP4 genotype occurred most frequently overall (66%), and
      the P4 genotype was detected next most frequently. The P6 genotype was identified
      in 28 symptomatically infected neonates and in 8 symptomatic infants. Few P9
      strains were identified. The potential for reassortment events was demonstrated
      by dual infections with different viruses.

PMID- 7650178
TI  - Correlation between phenotypic characteristics and DNA relatedness within
      Enterococcus faecium strains.
AB  - We noted that a number of enterococcal strains isolated from human clinical
      specimens resembled Enterococcus faecium but were able to produce acid from
      glycerol, raffinose, and/or sorbitol, while others failed to form acid from
      mannitol. An additional concern was that many of these strains with atypical
      phenotypic characteristics also appeared to acquire vancomycin resistance. In
      order to determine if such atypical strains were variants of E. faecium or new
      Enterococcus species, 35 E. faecium or E. faecium-like strains (grouped into 10
      phenotypes on the basis of the results of the following tests: capacity to form
      acid from glycerol, mannitol, raffinose, or sorbitol and susceptibility to
      vancomycin) and four strains of Enterococcus faecalis were taken from our culture
      collection, analyzed for their whole-cell protein profiles by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis, and identified to the species level
      by DNA-DNA reassociation experiments. All E. faecium-like strains, including four
      mannitol-negative variants, conformed to at least two of three DNA-DNA
      relatedness criteria: they were 70% or more related to the type strain of E.
      faecium at optimal conditions, they had less than 5% divergence within the
      related sequences, and they had a relatedness of 60% or greater under stringent
      conditions. The protein profiles of atypical strains were similar to those of
      typical strains and were easily distinguishable from those of E. faecalis and
      other enterococcal species. The five E. faecalis strains were 12 to 16% related
      to the E. faecium type strain. These results indicate that the phenotypic
      description of E. faecium should include all of these variable characteristics.

PMID- 7650179
TI  - Ability of commercial and reference antimicrobial susceptibility testing methods
      to detect vancomycin resistance in enterococci.
AB  - We evaluated the abilities of 10 commercially available antimicrobial
      susceptibility testing methods and four reference methods (agar dilution, broth
      microdilution, disk diffusion, and the agar screen plate) to classify enterococci
      correctly as vancomycin susceptible or resistant using 50 well-characterized
      strains of enterococci. There was a high level of agreement of category
      classification data obtained with broth-based systems (Sceptor, MicroMedia,
      Pasco, and Sensititre), agar dilution, and an antibiotic gradient method (E test)
      with data obtained by reference broth microdilution; no very major or major
      errors were seen, and minor errors were < or = 6%. Increased minor error rates
      were observed with disk diffusion (12%), Alamar (16%), Uniscept (16%), and
      conventional (overnight) MicroScan panels (16%). The errors were primarily with
      Enterococcus casseliflavus strains and organisms containing the vanB vancomycin
      resistance gene. Very major error rates of 10.3 and 20.7% were observed with
      Vitek and MicroScan Rapid (MS/Rapid) systems, respectively; however, only the
      MS/Rapid system produced major errors (13.3%). On repeat testing of discrepant
      isolates, the very major error rate with the Vitek system dropped to 3.4%, while
      the very major error rate with the MS/Rapid system increased to 27.6%; major
      errors with the MS/Rapid system were not resolved. Many of the commercial systems
      had only 4 dilutions of vancomycin, which resulted in up to 84% of values being
      off scale (e.g., Uniscept). Of the methods tested, most conventional broth- and
      agar-based methods proved to be highly accurate when incubation was done for a
      full 24 h, although several of the tests had high minor error rates. Automated
      systems continued to demonstrate problems in detecting low-level resistance.

PMID- 7650180
TI  - New Nocardia taxon among isolates of Nocardia brasiliensis associated with
      invasive disease.
AB  - Nocardia brasiliensis, the second most frequently isolated aerobic actinomycete
      in the clinical laboratory, is usually associated with localized cutaneous
      infections. However, 22% of 238 N. brasiliensis isolates from the United States
      and 12% of 66 isolates from Queensland, Australia, which had been collected over
      a 17-year period, were associated with extracutaneous and/or disseminated
      diseases. Of the 62 invasive isolates, 37 (60%) were susceptible to ciprofloxacin
      and/or were susceptible to clarithromycin and resistant to minocycline, compared
      with only 6 (3%) of 242 localized cutaneous isolates. The 43 isolates with this
      susceptibility pattern appeared to define a new taxon. They were similar to
      Nocardia asteroides complex isolates clinically in proportions from persons with
      pulmonary (70%), central nervous system (23%), and/or disseminated diseases (37%)
      in the setting of corticosteroids (74%) or AIDS (14%). This putative new taxon
      differed from N. brasiliensis in the hydrolysis of adenine (92 versus 4%), beta
      lactamase patterns on isoelectric focusing, and the presence of two early mycolic
      acid-ester peaks by high-performance liquid chromatography. Restriction analysis
      of a 439-bp fragment of the 65-kDa heat shock protein gene revealed that N.
      brasiliensis and the new taxon had different restriction patterns with 8 of the
      11 enzymes tested. Screening of invasive isolates of N. brasiliensis for
      susceptibility to ciprofloxacin will identify most isolates of the new taxon,
      which likely represents a new Nocardia species.

PMID- 7650181
TI  - Arbitrarily primed PCR DNA fingerprinting of Escherichia coli O157:H7 strains by
      using templates from boiled cultures.
AB  - Arbitrarily primed PCR allows genetically different bacterial strains to be
      distinguished with great sensitivity and efficiency. We report that informative,
      reproducible arbitrarily primed PCR profiles can be obtained from Escherichia
      coli O157:H7 strains by using boiled stationary-phase cultures, without the need
      for time-consuming phenol extraction. This simple template preparation procedure
      should be especially useful in large epidemiologic studies when many strains must
      be typed.

PMID- 7650183
TI  - Selective utilization of DNA probes for identification of Mycobacterium species
      on the basis of cord formation in primary BACTEC 12B cultures.
AB  - Primary BACTEC 12B cultures with serpentine cords observed in Kinyoun-stained
      smears were tested with a probe for Mycobacterium tuberculosis complex, while
      cultures without cords were tested with a probe for M. avium complex. The
      sensitivity, specificity, and positive and negative predictive values of cording
      for the presumptive identification of M. tuberculosis were 95, 95, 90, and 98%,
      respectively. With experience, the selection of a probe for testing of primary
      BACTEC 12B cultures on the basis of cord formation and history of tuberculosis
      can provide a rapid and reliable approach to the laboratory diagnosis of
      tuberculosis.

PMID- 7650182
TI  - Multicenter evaluation of arbitrarily primed PCR for typing of Staphylococcus
      aureus strains.
AB  - Fifty-nine isolates of Staphylococcus aureus and a single strain of
      Staphylococcus intermedius were typed by arbitrarily primed PCR (AP-PCR). To
      study reproducibility and discriminatory abilities, AP-PCR was carried out in
      seven laboratories with a standardized amplification protocol, template DNA
      isolated in a single institution, and a common set of three primers with
      different resolving powers. The 60 strains could be divided into 16 to 30
      different genetic types, depending on the laboratory. This difference in
      resolution was due to differences in technical procedures (as shown by the
      deliberate introduction of experimental variables) and/or the interpretation of
      the DNA fingerprints. However, this did not hamper the epidemiologically correct
      clustering of related strains. The average number of different genotypes
      identified exceeded those of the more traditional typing strategies (F. C.
      Tenover, R. Arbeit, G. Archer, J. Biddle, S. Byrne, R. Goering, G. Hancock, G. A.
      Hebert, B. Hill, R. Hollis, W. R. Jarvis, B. Kreiswirth, W. Eisner, J. Maslow, L.
      K. McDougal, J. M. Miller, M. Mulligan, and M. A. Pfaller, J. Clin. Microbiol.
      32:407-415, 1994). Comparison of AP-PCR with pulsed-field gel electrophoresis
      (PFGE) indicated the existence of strains with constant PFGE types but variable
      AP-PCR types. The reverse (constant AP-PCR and variable PFGE patterns) was also
      observed. This indicates additional resolution for combined analyses. It is
      concluded that AP-PCR is well suited for genetic analysis and monitoring of
      nosocomial spreading of staphylococci. The interlaboratory reproducibility of DNA
      banding patterns and the intralaboratory standardization need improvement.

PMID- 7650184
TI  - Comparison of BioStar Strep A OIA optical immune assay, Abbott TestPack Plus
      Strep A, and culture with selective media for diagnosis of group A streptococcal
      pharyngitis.
AB  - We directly compared three techniques for the diagnosis of group A streptococcal
      pharyngitis in 500 symptomatic children seen in the Emergency Department or Child
      Care Clinic of The Children's Hospital of Denver. Throats were vigorously swabbed
      with two rayon swabs, which were transported immediately to the Microbiology
      Laboratory. Each swab was cultured aerobically on Strep A Isolation Agar (Remel)
      and then tested for antigen-one swab by the Strep A OIA optical immune assay
      (BioStar) and the other by the TestPack Plus Strep A (Abbott) technique. Each
      test was performed blind to the others. The refrigerated pledget was cultured in
      Todd-Hewitt broth if an antigen test was positive and both direct plate cultures
      were negative (the "gold standard" was any culture positive). All isolates were
      serologically grouped. Of 500 complete patient cultures, 151 (30%) were positive
      for group A streptococcal growth. The two antigen tests gave comparable results
      with an average sensitivity of 83%. Each was significantly (P < 0.02) less
      sensitive than its corresponding culture. The BioStar Strep A OIA optical immune
      assay produced significantly (P < 0.003) more false-positive results than did the
      Abbott test. Rapid antigen testing is not sensitive enough to eliminate the need
      for backup cultures.

PMID- 7650186
TI  - Ethanol fixation of sputum sediments for DNA-based detection of Mycobacterium
      tuberculosis.
AB  - The effect of ethanol fixation on PCR detection and viability of Mycobacterium
      tuberculosis in human sputum sediments was evaluated. M. tuberculosis seeded into
      sputum sediments was efficiently killed when treated for 1 h with 50, 70, or 95%
      ethanol. PCR amplification of a 123-bp fragment of the M. tuberculosis-specific
      IS6110 was not affected in ethanol-treated samples even when fixation was
      extended to 24 h. Ethanol fixation of sputum sediments did not affect the PCR
      detection of M. tuberculosis in clinical samples. PCR results from ethanol
      treated clinical samples containing M. tuberculosis (smear positive and smear
      negative) or other respiratory pathogens correlated directly with the results by
      conventional detection methods for M. tuberculosis. Our results show that ethanol
      fixation of human sputum sediments containing M. tuberculosis significantly
      reduces the potential exposure of workers to viable M. tuberculosis without
      affecting DNA analysis by PCR. Also, ethanol fixation of sputum sediments
      provides a simple and inexpensive way to store and transport clinical specimens
      identified for DNA-based diagnostics without refrigeration.

PMID- 7650185
TI  - Comparison of field inversion gel electrophoresis with contour-clamped
      homogeneous electric field electrophoresis as a typing method for Enterococcus
      faecium.
AB  - Direct comparisons between contour-clamped homogeneous electric field (CHEF)
      electrophoresis and field inversion gel electrophoresis (FIGE) to determine the
      epidemiology of antibiotic-resistant enterococci have not been previously
      published. Fifty non-beta-lactamase-producing, ampicillin-resistant Enterococcus
      faecium isolates and 10 vancomycin-resistant E. faecium strains collected from
      multiple centers were analyzed in a blinded fashion by CHEF electrophoresis and
      FIGE after digestion with SmaI. Isolates were considered clonally related if
      there was a difference of three of fewer bands between electrophoretic patterns.
      Agreement between CHEF electrophoresis and FIGE was seen for 12 of 13 identified
      groups of ampicillin-resistant E. faecium and 7 of 7 groups of vancomycin
      resistant E. faecium. The lone discordance was accounted for by a fourth band
      difference between two strains recognized near 350 kb by CHEF electrophoresis but
      not by FIGE, placing them into different clonal groups. Better band separation
      was noted in the 50- to 200-kb range for FIGE, while CHEF electrophoresis
      revealed better resolution over 250 kb more reliably, including detection of some
      bands not seen on FIGE. Molecular epidemiologic investigations of E. faecium by
      either technique should provide comparable results.

PMID- 7650187
TI  - Comparative stabilities of quantitative human immunodeficiency virus RNA in
      plasma from samples collected in VACUTAINER CPT, VACUTAINER PPT, and standard
      VACUTAINER tubes.
AB  - This study compared the levels of human immunodeficiency virus (HIV) virion RNA
      in plasma from whole blood collected in VACUTAINER CPT (cell preparation tube),
      VACUTAINER PPT (plasma preparation tube), VACUTAINER SST (serum separation tube),
      and standard VACUTAINER tubes with sodium heparin, acid citrate dextrose, sodium
      citrate, and potassium EDTA used as anticoagulants. Quantitative plasma HIV RNA
      levels were measured by branched-DNA signal amplification. Blood from all tubes
      was either processed within 1 to 3 h after collection or stored at room
      temperature or at 4 degrees C for analysis at 6 to 8 and 30 h postdraw.
      Immediately separated plasma from sodium citrate CPT tubes held at 4 degrees C
      maintained better stability of HIV RNA equivalents than whole blood held at room
      temperature or 4 degrees C. The highest number of HIV RNA equivalents was seen
      with EDTA VACUTAINER tubes. HIV RNA equivalents in all types of plasma were
      significantly higher than in SST tubes. Although a decline in HIV RNA equivalents
      was seen in all collection devices after 30 h, a significantly greater decline in
      plasma HIV RNA equivalents occurred in acid citrate dextrose VACUTAINER tubes
      than in citrate CPT, PPT, and standard EDTA VACUTAINER tubes. In order to
      minimize the variability of quantitative HIV RNA test results, our data suggest
      that samples collected for a particular assay should be processed at the same
      time postdraw using a particular tube type throughout a given study.

PMID- 7650188
TI  - Clinical and epidemiological investigations of Acinetobacter genomospecies 3 in a
      neonatal intensive care unit.
AB  - A prospective study of Acinetobacter isolates from a neonatal intensive care unit
      was performed for 24 months. Fifty-six isolates were obtained from 21 patients,
      and another eight were obtained from environmental specimens. Infection due to
      Acinetobacter organisms was established for 16 patients, 6 with septicemia, 9
      with pneumonia, and 1 with a wound infection. Further investigations were
      performed with 38 representative isolates. Twenty-nine isolates were identified
      as unnamed DNA-DNA hybridization group (genomospecies) 3, three were identified
      as genomospecies 2 (Acinetobacter baumannii), one was identified as genomospecies
      5 (Acinetobacter junii), three were identified as genomospecies 14, and two were
      unclassified. Eight distinguishable protein profiles, coded I through VIII, were
      found by cell envelope protein electrophoresis. Profile V, a common profile, was
      observed for 17 isolates that had been recovered from 11 patients and 1 dust
      specimen. These isolates, all of which belonged to genomospecies 3, had similar
      antibiograms and biotypes. This study has revealed that genomospecies 3 can be
      associated with infection and be spread in hospitals.

PMID- 7650190
TI  - Detection of Epstein-Barr virus DNA in cerebrospinal fluid for diagnosis of AIDS
      related central nervous system lymphoma.
AB  - The diagnostic utility of Epstein-Barr virus (EBV) DNA detection in cerebrospinal
      fluid for the diagnosis of central nervous system lymphoma was evaluated with two
      different PCR assays to test a collection of cerebrospinal fluid samples from 24
      AIDS patients with central nervous system disorders. A PCR assay amplifying a
      fragment from the BamHI-W region had the highest clinical and analytic
      sensitivity. The BamHI-W PCR assay detected EBV DNA in cerebrospinal fluid from
      83% (5 of 6) of patients with pathologically proven primary central nervous
      system lymphoma and 7% (1 of 16) of controls with autopsy-proven nonlymphomatous
      central nervous system disorders. EBV DNA was also detected in one patient with
      autopsy-proven systemic lymphoma involving the central nervous system and one
      patient with probable primary central nervous system lymphoma. EBV DNA was
      detected consistently when central nervous system lymphoma involved meningeal
      surfaces. PCR for EBV in cerebrospinal fluid appears to be useful for diagnosis
      of AIDS-related central nervous system lymphoma, but additional studies are
      required to better define the sensitivity of the assay and to understand the
      significance of a positive test in the absence of lymphoma.

PMID- 7650191
TI  - Analysis of enzymatic activities for differentiation of two species of
      nutritionally variant streptococci, Streptococcus defectivus and Streptococcus
      adjacens.
AB  - Strains of nutritionally variant streptococci, Streptococcus defectivus (n = 10)
      and Streptococcus adjacens (n = 20), were studied for the production of
      glycosidic and proteolytic enzyme activities. S. defectivus strains produced
      neuraminidase and alpha-fucosidase, while S. adjacens strains produced only
      neuraminidase. The S. adjacens strains produced a very wide range of proteolytic
      activities with the ability to hydrolyze the majority of aminopeptidase
      substrates tested, while S. defectivus strains hydrolyzed only a minority of
      aminopeptidase substrates. These data provide additional phenotypic
      characteristics which may be useful in distinguishing between these two species
      and suggest that they may have different nutritional requirements.

PMID- 7650189
TI  - Inter- and intraspecies identification of Bartonella (Rochalimaea) species.
AB  - Species of the genus Rochalimaea, recently renamed Bartonella, are of a growing
      medical interest. Bartonella quintana was reported as the cause of trench fever,
      endocarditis, and bacillary angiomatosis. B. henselae has been implicated in
      symptoms and infections of human immunodeficiency virus-infected patients, such
      as fever, endocarditis, and bacillary angiomatosis, and is involved in the
      etiology of cat scratch disease. Such a wide spectrum of infections makes it
      necessary to obtain an intraspecies identification tool in order to perform
      epidemiological studies. B. vinsonii, B. elizabethae, seven isolates of B.
      quintana, and four isolates of B. henselae were studied by pulsed-field gel
      electrophoresis (PFGE) after restriction with the infrequently cutting
      endonucleases NotI, EagI, and SmaI. Specific profiles were obtained for each of
      the four Bartonella species. Comparison of genomic fingerprints of isolates of
      the same species showed polymorphism in DNA restriction patterns, and a specific
      profile was obtained for each isolate. A phylogenetic analysis of the B. quintana
      isolates was obtained by using the Dice coefficient, UPGMA (unweighted pair-group
      method of arithmetic averages), and Package Philip programming. Amplification by
      PCR and subsequent sequencing using an automated laser fluorescent DNA sequencer
      (Pharmacia) was performed on the intergenic spacer region (ITS) between the 16
      and 23S rRNA genes. It was found that each B. henselae isolate had a specific
      sequence, while the B. quintana isolates fell into only two groups. When
      endonuclease restriction analysis of the ITS PCR product was done, three enzymes,
      TaqI, HindIII, and HaeIII, allowed species identification of Bartonella spp.
      Restriction fragment length polymorphism after PCR amplification of the 16S-23S
      rRNA gene ITS may be useful for rapid species identification, and PFGE could be
      an efficient method for isolate identification.

PMID- 7650193
TI  - Species identification of members of the Streptococcus milleri group isolated
      from the vagina by ID 32 Strep system and differential phenotypic
      characteristics.
AB  - The importance of bacterial vaginosis as a risk factor in obstetric and
      gynecological infections has recently been recognized. The bacterial vaginosis
      group of organisms includes members of the Streptococcus milleri group, the
      identification of which has caused much confusion. We prospectively surveyed the
      rates of carriage of S. milleri group organisms in 397 high vaginal swabs
      received in our laboratory. For the identification of 99 clinical isolates and 23
      control strains, we compared the results obtained by the rapid ID 32 Strep system
      (Analytab Products) and by a scheme utilizing six differential phenotypic
      characteristics (presence of beta-N-acetylglucosaminidase, alpha-glucosidase,
      beta-D-fucosidase, beta-galactosidase, beta-N-acetylgalactosaminidase, and beta
      glucosidase) as described by Whiley et al. (R. A. Whiley, H. Fraser, J. M.
      Hardie, and D. Beighton, J. Clin. Microbiol. 28:1497-1501, 1990). We identified
      Streptococcus anginosus in 18% and Streptococcus constellatus in 0.05% of the
      specimens examined. Of the isolates of S. anginosus that reacted with grouping
      antisera, 20 of 25 belonged to Lancefield group F. The incubation conditions for
      bacterial cultures and for reaction mixtures affected the results of phenotypic
      characterization in the production of alpha-glucosidase, beta-galactosidase, and
      beta-glucosidase. However, by using bacterial cultures grown under hypercapnic
      conditions and incubating the reaction mixtures aerobically, consistent
      phenotypic characteristics were obtained, allowing identification similar to that
      obtained by the ID 32 Strep system. We therefore recommend the phenotypic scheme
      as an inexpensive, reliable, and convenient method for the initial identification
      of species of the S. milleri group.

PMID- 7650192
TI  - Direct determination of cryptococcal antigen in transthoracic needle aspirate for
      diagnosis of pulmonary cryptococcosis.
AB  - Pulmonary cryptococcosis causes significant morbidity and mortality in
      immunocompromised patients. Definitive diagnosis of pulmonary cryptococcosis is
      usually difficult. The use of direct determination of cryptococcal antigen in
      transthoracic needle aspirate to diagnose pulmonary cryptococcosis was
      investigated. Over a 2-year period, we studied a total of 41 patients with
      respiratory symptoms and pulmonary infiltrates of unknown etiology who were
      suspected of having pulmonary cryptococcosis. Twenty-two patients were
      immunocompetent patients and 19 patients were immunocompromised. A diagnosis of
      pulmonary cryptococcosis was based on cytological examination, culture for
      Cryptococcus neoformans, histopathologic examination, and clinical response to
      antifungal therapy. All patients underwent chest ultrasound and ultrasound-guided
      percutaneous transthoracic needle aspiration to obtain specimens for cryptococcal
      antigen determination. The presence of cryptococcal antigen was determined by the
      latex agglutination system (CALAS; Meridian Diagnostics, Cincinnati, Ohio). An
      antigen titer equal to or greater than 1:8 was considered positive. The specimens
      were also sent for cytological examination, fungal culture, and/or
      histopathologic examination. A final diagnosis of pulmonary cryptococcosis was
      made in eight patients. Direct determinations of cryptococcal antigen in lung
      aspirate were positive in all eight patients with pulmonary cryptococcosis (100%
      sensitivity, 97% specificity, a positive predictive value of 89%, and negative
      value of 100%), and there was only one false-positive in noncryptococcosis
      patients. The diagnostic accuracy was 97.5%. Serum cryptococcal antigen was
      positive in only three patients with pulmonary cryptococcosis (sensitivity,
      37.5%). This study showed that direct measurement of cryptococcal antigen in lung
      aspirate can be a rapid and useful test for diagnosis of pulmonary
      cryptococcosis.

PMID- 7650194
TI  - Comparison of three typing methods for clinical and environmental isolates of
      Aspergillus fumigatus.
AB  - To evaluate procedures used for epidemiologic analysis of outbreaks of
      aspergillosis, we analyzed a collection of 35 Aspergillus fumigatus isolates
      using three typing methods: isoenzyme analysis (IEA), random amplified
      polymorphic DNA (RAPD) analysis, and restriction endonuclease analysis (REA).
      Twenty-one isolates were from a single hospital, with four isolates coming from
      different patients. Three clinical isolates came from a different hospital, and
      11 clinical or environmental isolates were derived from a culture collection.
      With IEA, the patterns of alkaline phosphatase, esterase, and catalase
      discriminated nine types. In contrast, 22 types were obtained with five different
      RAPD primers, and 21 types could be detected with three of these (R108, R151, and
      UBC90). Restriction endonuclease analysis of genomic DNA, digested with either
      XbaI, XhoI, or SalI, detected 3, 17, and 13 different REA types, respectively,
      and 22 types were identified by combining the data from the XhoI and SalI REAs.
      Twenty-eight types were obtainable with a combination of REA, IEA, and RAPD
      patterns. Overall, the results pointed to substantial genetic variation among the
      isolates. Though two isolates had markedly distinct genotypes, their morphologic
      features and exoantigens were consistent with their being A. fumigatus. The
      analysis will help in planning epidemiologic studies of aspergillosis.

PMID- 7650195
TI  - Long-term shedding and clonal turnover of enterohemorrhagic Escherichia coli O157
      in diarrheal diseases.
AB  - To investigate the length of time that Shiga-like toxin-producing Escherichia
      coli O157 is excreted after the onset of diarrhea, 456 serial stool specimens
      were obtained from 53 children. E. coli O157 cells were identified by the use of
      DNA probes followed by agglutination with a specific antiserum. Specimens were
      collected until three consecutive stool samples (collected within 9 days) were
      negative for E. coli O157. The median durations of shedding were 13 days (range,
      2 to 62 days) in patients with diarrhea or hemorrhagic colitis and 21 days
      (range, 5 to 124 days) in patients that developed hemolytic uremic syndrome. In
      36 (68%) of the patients, only the first culture was O157 positive, and the three
      cultures that followed were negative. In 7 (13%) of the patients, E. coli O157
      cells were shed for more than 32 days after the onset of diarrhea; these long
      term shedders were clinically asymptomatic by the end of this period. In 12
      patients, one or two serial O157-negative cultures, obtained up to 8 days after a
      positive culture, were followed by another positive culture. Comparison of the
      first and last E. coli O157 isolates by pulsed-field gel electrophoresis revealed
      that in three of the seven long-term shedders, pulsed-field gel electrophoresis
      types varied. In two cases, a Shiga-like toxin gene was apparently lost during
      infection. The observation of long-term shedding accompanied by genotypic
      turnover has epidemiological and diagnostic implications.

PMID- 7650196
TI  - Comparative study of five different DNA fingerprint techniques for molecular
      typing of Streptococcus pneumoniae strains.
AB  - The aim of this study was to identify the strengths and weaknesses of five DNA
      fingerprint methods for epidemiological typing of Streptococcus pneumoniae. We
      investigated the usefulness of (i) ribotyping, (ii) BOX fingerprinting with the
      BOX repetitive sequence of S. pneumoniae as a DNA probe, (iii) PCR fingerprinting
      with a primer homologous to the enterobacterial repetitive intergenic consensus
      sequence, (iv) pulsed-field gel electrophoresis of large DNA fragments, and (v)
      restriction fragment end labeling to detect restriction fragment length
      polymorphism of small DNA fragments. Twenty-eight S. pneumoniae strains isolated
      from the blood and/or cerebrospinal fluid of 21 patients were analyzed. Genetic
      clustering among the 28 strains was independent of the DNA fingerprint technique
      used. However, the discriminatory power and the similarity values differed
      significantly among the individual techniques. BOX fingerprinting, pulsed-field
      gel electrophoresis, and restriction fragment end labeling provided the highest
      degree of discriminatory power. Furthermore, the ease with which computerized
      fingerprint analysis could be conducted also varied significantly among the
      techniques. Ribotyping, BOX fingerprinting, and restriction fragment end labeling
      were very suitable techniques for accurate computerized data analysis. Because of
      their high discriminatory potential and ease of accurate analysis, we conclude
      that BOX fingerprinting and restriction fragment end labeling are the most
      suitable techniques to type pneumococcal strains.

PMID- 7650197
TI  - Experience with a novel selective medium for isolation of Actinomyces spp. from
      medical and dental specimens.
AB  - A selective medium containing mupirocin and metronidazole was evaluated for the
      isolation of Actinomyces spp. from clinical material. The study was a one-year
      prospective comparison of the method with existing methods, which use
      nonselective media, at a general hospital and a dental hospital. Significantly
      more Actinomyces spp. were isolated on the selective medium than on nonselective
      media from both dental specimens and intrauterine contraceptive devices. However,
      differentiating between Actinomyces spp. and related nonsporulating gram-positive
      rods remains a slow and sometimes uncertain process which can introduce lengthy
      delays in reporting.

PMID- 7650198
TI  - Genotypic detection of Mycobacterium tuberculosis rifampin resistance: comparison
      of single-strand conformation polymorphism and dideoxy fingerprinting.
AB  - Detection of mutations in the rpoB gene of Mycobacterium tuberculosis can be used
      as an accurate predictor of rifampin resistance in the majority of strains
      tested. Simple but highly accurate screening methods must be developed for the
      detection of these mutations. Either DNA sequence analysis or single-strand
      conformation polymorphism (SSCP) screening can be used to detect rpoB mutations,
      but these techniques either are expensive or yield results that may prove
      difficult to interpret when used in a clinical setting. This report describes the
      use of dideoxy fingerprinting (ddF) as a postamplification screening method to
      identify rifampin-resistant genotypes. The ddF protocol was performed on the
      amplified rpoB fragment with no preparatory steps, thus making ddF practical for
      laboratories equipped for polyacrylamide gel electrophoresis. When compared with
      the results of SSCP analysis, ddF results were more easily interpreted and
      contained more sequence-dependent information that facilitated differentiation of
      functionally significant and silent mutations. The ddF method was used for
      genotypic determination of rifampin susceptibility of 20 multidrug-resistant
      strains of M. tuberculosis. The results of this analysis were concordant with DNA
      sequence analysis and conventional clinical laboratory methods.

PMID- 7650199
TI  - Identification of virulent Rhodococcus equi by amplification of gene coding for
      15- to 17-kilodalton antigens.
AB  - During a survey of the prevalence of virulent Rhodococcus equi at horse-breeding
      farms by plasmid and protein profiles, cryptic plasmids of various sizes were
      found in 66 (3.8%) of 1,725 isolates from feces of horses and 129 (5.9%) of 2,200
      isolates from soil. Twenty-two isolates, which contained cryptic plasmids of
      different sizes, were found by plasmid profiles, and their protein profiles and
      mouse pathogenicities were examined. Of the 22 isolates, 7 were virulent R. equi,
      contained both virulence and cryptic plasmids, and expressed 15- to 17-kDa
      antigens. The remaining 15 isolates were avirulent and did not express the
      antigens: 6 strains contained cryptic plasmids of two different sizes and 9
      strains contained cryptic plasmids of various sizes. A PCR assay was developed
      for the rapid identification of virulence plasmids of R. equi. Oligonucleotide
      primers, derived from the sequence of a gene coding for the 15- to 17-kDa
      virulence-associated antigens of R. equi, amplified a 564-bp product from all the
      tested isolates harboring a virulence plasmid. This PCR product hybridized with
      virulence plasmid DNA in the Southern hybridization assay. Virulence plasmid
      cured derivatives and all of the tested isolates harboring cryptic plasmids only
      were negative. The PCR is a rapid, sensitive, and specific test for the
      identification of virulent R. equi from environmental isolates compared with
      standard techniques, such as plasmid and protein profiles and the mouse
      pathogenicity test, and is considered to be a useful tool for epidemiological
      studies.

PMID- 7650200
TI  - Immunoglobulin M capture immunoassay in investigation of coxsackievirus B5 and B6
      outbreaks in South Australia.
AB  - An immunoglobulin M (IgM) capture enzyme immunoassay was used to detect major
      overlapping outbreaks of disease in South Australia caused by coxsackieviruses B5
      (CBV-5) and B6 (CBV-6). CBV-5-specific IgM was detected in patients presenting in
      spring 1992 with acute febrile illnesses, rash, severe acute respiratory disease,
      meningitis, myocarditis and/or pericarditis, while tests for other viruses were
      negative. CBV-5 was isolated from an early case. In December 1992 it was noted
      that CBV-6 had replaced CBV-5 as the major cause of disease. The CBV-6 epidemic
      continued until April 1993. Serum samples from 495 patients (276 inpatients) were
      submitted for testing. CBV-6 infection was associated with lower respiratory
      tract infection and persistent cough. This study demonstrated success of the IgM
      enzyme immunoassay and the need for diagnostic virology laboratories to look for
      CBV-6 infection in addition to the other five CBVs.

PMID- 7650201
TI  - Relevance of culturing Candida species from intravascular catheters.
AB  - The significance of isolating Candida species from intravascular catheters was
      examined retrospectively. Our findings demonstrate that these organisms are
      encountered among patients with proven invasive candidiasis or as an isolated
      finding. Febrile patients with yeasts in two or more additional sites may be at
      risk for invasive cadidiasis and may benefit from treatment.

PMID- 7650202
TI  - Helcococcus, a new genus of catalase-negative, gram-positive cocci isolated from
      clinical specimens.

PMID- 7650203
TI  - Enhancement of the Brucella AMOS PCR assay for differentiation of Brucella
      abortus vaccine strains S19 and RB51.
AB  - Because the brucellosis eradication program uses slaughter and quarantine as
      control measures, it would benefit from faster methods of bacterial
      identification. Distinguishing vaccine strains from strains that cause infections
      among vaccinated herds in the field is essential. To accomplish this, our PCR
      based, species-specific assay (B. J. Bricker and S. M. Halling, J. Clin.
      Microbiol. 32:2660-2666, 1994) was updated to identify Brucella abortus vaccine
      strains S19 and RB51. Three new oligonucleotide primers were added to the five
      primer multiplex Brucella AMOS PCR assay. Identification is based on the number
      and sizes of six products amplified by PCR.

PMID- 7650204
TI  - Investigation of the reformulated Remel Synergy Quad plate for detection of high
      level aminoglycoside and vancomycin resistance among enterococci.
AB  - We investigated the accuracy of the recently released Remel Synergy Quad plate, a
      commercially available agar screening method for detecting high-level
      aminoglycoside and vancomycin resistance among enterococci that is based on the
      National Committee for Clinical Laboratory Standards recommended guidelines
      (National Committee for Clinical Laboratory Standards, M7-A3, 1993). The Synergy
      Quad correctly determined the gentamicin and streptomycin resistance status for >
      or = 97% of 147 Enterococcus faecalis and Enterococcus faecium isolates tested.
      Detection of vancomycin resistance also was reliable, as no false susceptibility
      occurred with 36 vancomycin-resistant E. faecalis and E. faecium strains and
      false resistance occurred only once with the 47 susceptible strains tested. One
      strain each of Enterococcus gallinarum and Enterococcus casseliflavus failed to
      grow on the screen, but because the true nature and significance of resistance in
      such isolates is unknown the implication of their screen negativity is uncertain.
      In summary, the Remel Synergy Quad provides a highly accurate and convenient
      method for susceptibility testing of enterococci against gentamicin,
      streptomycin, and vancomycin.

PMID- 7650205
TI  - Comparison of several fixation methods for cytomegalovirus antigenemia assay.
AB  - Two fixation methods based on formaldehyde or acetone for qualitative
      cytomegalovirus antigenemia assay were evaluated on 405 consecutive blood
      samples. Cytomegalovirus was detected in 40 samples by the antigenemia assay: 36
      were detected by formaldehyde fixation; 22, by acetone; and 18, by both methods.
      Differences were statistically significant (P = 0.0043). In addition, four
      fixation methods (two based on formalin [with and without permeabilization] and
      two using acetone at different fixation times) for quantitative antigenemia assay
      in a different set of 32 samples from known viremic patients were evaluated.
      Formalin-based methods were superior to acetone-based methods, showing
      statistically significant differences in either the number of positive samples
      detected (P < 0.02; McNemar test) or the mean positive cell counts (P < 0.003;
      two-tailed Student's t test for paired samples). No differences between the two
      formalin-based methods were found. We recommend the formaldehyde fixation
      procedure without subsequent permeabilization because of its simplicity and
      sensitivity.

PMID- 7650206
TI  - Comparison of rapid immunofluorescence procedure with TestPack RSV and Directigen
      FLU-A for diagnosis of respiratory syncytial virus and influenza A virus.
AB  - A rapid immunofluorescence format requiring 20 min for completion was as
      effective as conventional indirect and direct immunofluorescence procedures for
      detecting respiratory syncytial virus and influenza A virus antigens in clinical
      specimens. Rapid immunofluorescence was more sensitive than TestPack RSV and
      comparable to Directigen FLU-A immunosorbent assays, which require 20 min for
      completion.

PMID- 7650207
TI  - Cloning and nucleotide sequence of a specific DNA fragment from Paracoccidioides
      brasiliensis.
AB  - We cloned and sequenced a species-specific 110-bp DNA fragment from
      Paracoccidioides brasiliensis. The DNA fragment was generated by PCR with primers
      complementary to the rat beta-actin gene under a low annealing temperature.
      Comparison of the nucleotide sequence, after excluding the primers, with those in
      the GenBank database identified approximately 60% homology with an exon of a
      major surface glycoprotein gene from Pneumocystis carinii and a fragment of
      unknown function in Saccharomyces cerevisiae chromosome VIII. By Southern
      hybridization analysis, the 32P-labelled fragment detected 1.0- and 1.9-kb
      restriction fragments within whole-cell genomic DNA of P. brasiliensis digested
      with HindIII and PstI, respectively, but failed to hybridize to genomic DNAs from
      Candida albicans, Blastomyces dermatitidis, Cryptococcus neoformans, Aspergillus
      fumigatus, Saccharomyces cerevisiae, Pneumocystis carinii, rat tissue, or humans
      under low-stringency hybridization conditions. Additionally, the specific DNA
      fragment from three different P. brasiliensis isolates (Pb18, RP18, RP17) was
      amplified by PCR with primers mostly complementary to nonactin sequences of the
      110-bp DNA fragment. In contrast, there were no amplified products from other
      fungus genomic DNAs previously tested, including Histoplasma capsulatum. To date,
      this is the first species-specific DNA fragment cloned from P. brasiliensis which
      might be useful as a diagnostic marker for the identification and classification
      of different P. brasiliensis isolates.

PMID- 7650208
TI  - Randomly amplified polymorphic DNA analysis provides rapid differentiation of
      methicillin-resistant coagulase-negative staphylococcus bacteremia isolates in
      pediatric hospital.
AB  - Coagulase-negative staphylococci (CoNS) are now recognized as the most common
      cause of nosocomial bacteremia in pediatric patients. Randomly amplified
      polymorphic DNA analysis was used to study the relationships among 12 isolates of
      CoNS obtained from eight patients with catheter-related bacteremia in two
      distinct wards of our hospital and 6 epidemiologically unrelated strains. With
      this method, we were able to discriminate isolates that otherwise were
      indistinguishable by conventional criteria such as biochemical typing and
      antibiotic susceptibility patterns. Our results indicate that there were episodes
      of cross-infections among four patients in one ward but independent infectious
      episodes among four patients in the other ward. Randomly amplified polymorphic
      DNA analysis is a rapid method which seems particularly well suited to the
      epidemiological study of CoNS isolates.

PMID- 7650209
TI  - Human herpesvirus 6 and human herpesvirus 7 in chronic fatigue syndrome.
AB  - We analyzed lymphocytes of patients with chronic fatigue syndrome (CFS) for the
      presence of human herpesvirus 6 (HHV-6) and HHV-7 DNA. HHV-7 was present in over
      80% of CFS patients and healthy controls, while the prevalence of HHV-6 variant A
      increased significantly in CFS cases (22 versus 4%; P = 0.05).

PMID- 7650210
TI  - Quantitative competitive PCR with bronchoalveolar lavage fluid for diagnosis of
      toxoplasmosis in AIDS patients.
AB  - Of 121 AIDS patients, 12 (10%) had Toxoplasma gondii DNA detected by competitive
      PCR in their bronchoalveolar lavage samples. Quantitation of the PCR results
      showed a correlation between the parasite burden and the serum lactic
      dehydrogenase titer. Quantitative competitive PCR could be useful to assess the
      diagnosis and the severity of pulmonary toxoplasmosis.

PMID- 7650212
TI  - Description of feline nonsuppurative meningoencephalomyelitis ("staggering
      disease") and studies of its etiology.
AB  - A spontaneous neurological disease in domestic cats is described. The clinical
      signs included staggering gait, hind limb ataxia, and paresis. Histologically, a
      nonsuppurative meningoencephalomyelitis with a characteristic distribution
      pattern was found, indicating a viral etiology. In serum samples from diseased
      cats, antibodies to Borna disease virus were demonstrated.

PMID- 7650211
TI  - Multicenter clinical laboratory evaluation of a beta-lactamase disk assay
      employing a novel chromogenic cephalosporin, S1.
AB  - S1, a new chromogenic cephalosporin (International BioClinical, Inc., Portland,
      Oreg.), was used to detect beta-lactamase production among a variety of commonly
      encountered bacteria in a four-center collaborative study. Results of an S1 disk
      assay were compared with those obtained by a nitrocefin-based disk procedure
      (Cefinase; Becton-Dickinson Microbiology Systems, Cockeysville, Md.), with
      repetitive testing of five quality control organisms and with individual tests of
      recent clinical isolates of Neisseria gonorrhoeae (162 strains), Haemophilus
      influenzae (162 strains), Moraxella catarrhalis (155 strains), Staphylococcus
      aureus (161 strains), and Bacteroides fragilis (164 strains). The performances of
      the two beta-lactamase disk assays were comparable for the first three species
      cited above. However, the S1 assay appeared to be a more sensitive procedure than
      the Cefinase assay when applied to S. aureus and B. fragilis, with respect to
      both total numbers of positive results and length of time to a definitive
      positive endpoint.

PMID- 7650213
TI  - Quantitation of human immunodeficiency virus type 1 DNA and RNA by a novel
      internally controlled PCR assay.
AB  - A novel internally controlled PCR (ICPCR) assay was developed to accurately
      quantitate human immunodeficiency virus type 1 (HIV-1) DNA and RNA in peripheral
      blood mononuclear cells and plasma. The ICPCR assay was sensitive and
      reproducible within a linear range of amplification of 10(0) to 10(3) copies for
      HIV-1 DNA and 10(1) to 10(4) copies for HIV-1 RNA. The assay detected HIV-1 RNA
      in plasma and peripheral blood mononuclear cells from all HIV-1 subjects
      regardless of disease stage. ICPCR was compared with a branched-DNA signal
      amplification assay for subjects beginning antiretroviral therapy. The reductions
      in plasma HIV-1 RNA in response to therapy were comparable with the two assays.
      The ICPCR assay should be useful in monitoring HIV-1 RNA levels both in natural
      history studies and in clinical trials of antiretroviral agents.

PMID- 7650214
TI  - False-positive cryptococcal antigen latex agglutination caused by disinfectants
      and soaps.
AB  - Five disinfectants or soaps were tested to determine if any could be responsible
      for false-positive results obtained with the Latex-Crypto Antigen Detection
      System kit (Immuno-Mycologics, Inc., Norman, Okla.). Three disinfectants or soaps
      (Derma soap, 7X, and Bacdown) produced false-positive agglutination after
      repeated washing of ring slides during testing of a known negative cerebrospinal
      fluid specimen.

PMID- 7650215
TI  - Analysis of strains of Campylobacter fetus by pulsed-field gel electrophoresis.
AB  - Campylobacter fetus chromosomal DNA from 21 strains was analyzed by pulsed-field
      gel electrophoresis. The fingerprint patterns generated with SmaI and SalI were
      distinctive. Using the profiles obtained by pulsed-field gel electrophoresis, we
      established the phylogenetic dendrogram of C. fetus to identify the genetic
      relationship of the strains.

PMID- 7650216
TI  - Genotyping of hepatitis C virus in South Africa.
AB  - The six major hepatitis C virus genotypes were investigated by using samples from
      79 seropositive and PCR-positive blood donors from three different regions of
      South Africa as well as 9 patients with chronic renal failure, 19 with liver
      disease, and 23 with hemophilia. PCR products of the genome were typed by
      restriction fragment length polymorphic analysis by RsaI-HaeIII and MvaI-HinfI
      double digestion. Type 5 occurred in 40% of this population group; type 1
      occurred in 33%; and types 2, 3, and 4 were found in 13.8, 7.7, and 2.3%,
      respectively.

PMID- 7650217
TI  - Involvement of multiple Cryptococcus neoformans strains in a single episode of
      cryptococcosis and reinfection with novel strains in recurrent infection
      demonstrated by random amplification of polymorphic DNA and DNA fingerprinting.

PMID- 7650218
TI  - Cryptosporidium antigen detection in human feces by reverse passive
      hemagglutination assay.

PMID- 7650219
TI  - Presidential address. American College of Clinical Pharmacology has provided a
      variety of educational opportunities.
AB  - At the current time, the College is in an excellent position to support the
      educational needs of its growing membership. The fund balance has increased over
      the past few years and is continuing to increase during the current year. The
      unprecedented speed of changes in the health care environment in which all
      clinical pharmacologists are now working necessitates that the American College
      of Clinical Pharmacology continually examine and update its Strategic Plan and
      Long Range Goals to allow all of its members to keep abreast of these changes. As
      hospitals, medical schools, and other allied health colleges address the need for
      economic accountability, as educators in medical and pharmacy and other schools
      encounter state and federal reductions in financial assistance to students, and
      as new roles are developed for the clinical pharmacologists working within the
      professions of medicine, pharmacy and allied health specialties, the College must
      maintain its role as a leader for all clinical pharmacologists. The success of
      the College will be directly related to the effort invested by all of the
      committee members and chairpersons, the Board of Regents, the Officers of the
      College, and most of all, the membership. During the next two years, I look
      forward to working with the entire membership to encourage growth of the College.

PMID- 7650220
TI  - The expanding role of angiotensin converting enzyme inhibitors in the management
      of hypertension.
AB  - Angiotensin converting enzyme (ACE) inhibitors are increasingly important in
      antihypertensive therapy because of their efficacy, tolerability, and specific
      benefits in subsets of patients. They are pharmacologically diverse. Whereas most
      benefits have been proven with older agents (captopril, enalopril), newer agents,
      such as benazepril, quinapril, and ramipril, offer potential advantages that
      remain to be proven.

PMID- 7650221
TI  - Cyclic antidepressant toxicity in children and adolescents.
AB  - We retrospectively evaluated the clinical and laboratory findings of all patients
      admitted to our facility during a 6.5-year period with a history of cyclic
      antidepressant ingestion (CAD). Outcome parameters [admission CAD concentration,
      arterial pH, and corrected QT (QTc) and QRS intervals] used in adult populations
      to predict morbidity after CAD ingestion were applied to our study population.
      During the study period, 45 patients (mean +/- SD age of 11.8 +/- 5.6 years) were
      admitted with CAD ingestion. Conduction delays were present in 17 patients, 9 of
      whom had QTc intervals greater than 0.43 seconds. Seven patients had generalized
      seizures; 7 required mechanical ventilation; 14 had Glasgow Coma Scores of 8 or
      lower on presentation; and one required pharmacologic support for hypotension. In
      our cohort, the mean admission serum CAD concentration was 461.5 +/- 477.4 ng/mL.
      Correlations were found between the arterial pH, the QRS interval, the QTc
      interval, and the admission CAD serum concentration. In an analysis of three
      subsets of patients (i.e., those with seizures, coma, and respiratory
      insufficiency), only patients who presented with seizures were found to have a
      significant prolongation in the QRS and QTc intervals. Pediatric patients who
      have ingested CADs and present with seizures would appear to be at increased risk
      for having conduction delays, cardiac dysrhythmias, and, presumably, attendant
      morbidity and mortality associated with an ingestion.

PMID- 7650222
TI  - Risk factors for the development of specific noncardiovascular adverse effects
      associated with amiodarone.
AB  - Noncardiovascular adverse effects associated with amiodarone result in
      substantial morbidity. Adverse effects involving the skin, liver, thyroid, and
      lungs have been reported in as many as 57%, 55%, 11%, and 13% of patients,
      respectively. Although risk factors for some amiodarone-induced adverse effects
      have been identified, risk factors for these specific side effects have not been
      systematically evaluated. Therefore, risk factors for development of amiodarone
      induced dermatologic, hepatic, thyroid, or pulmonary adverse effects were
      identified using univariate analysis in 44 patients receiving the drug for
      supraventricular or ventricular arrhythmias (mean duration of therapy 99.5 +/-
      110.8 weeks). Dermatologic side effects occurred in 4 (9.1%) patients. Patients
      who experienced dermatologic side effects were younger than patients who did not
      (mean age, 48.3 +/- 15.8 years versus 60.1 +/- 9.5 years, respectively; P = .03).
      Patients younger than 60 years of age were more likely to develop
      photosensitivity or blue-gray skin discoloration than those aged 60 or older (P =
      .05). Hepatic adverse effects occurred in 3 (6.8%) patients. Left ventricular
      ejection fraction was lower in those who developed hepatic adverse effects than
      in those who did not (15.0 +/- 4.0% versus 39.1 +/- 13.9%, P = .005). Adverse
      thyroid effects occurred in 6 (13.6%) patients; and pulmonary fibrosis occurred
      in 2 (4.5%) patients. No specific risk factors for adverse thyroid effects or
      pulmonary fibrosis were revealed. In conclusion, age less than 60 may be a risk
      factor for amiodarone-induced dermatologic adverse effects, whereas severely
      depressed left ventricular ejection fraction may be a risk factor for hepatic
      side effects associated with amiodarone.

PMID- 7650223
TI  - High-grade nucleoside transport inhibition stimulates ventilation in humans.
AB  - In 6 healthy male volunteers a placebo-controlled, double-blind, randomized,
      crossover trial was done to assess the effect of 1, 2, 4, and 6 mg of draflazine,
      a specific nucleoside transport inhibitor, on ventilation. Draflazine increased
      thoracic excursions dose-dependently by maximally (median with 95% confidence
      interval) 114.0% (38.3-184.8%) without affecting breathing rate. Ex vivo
      adenosine transport was inhibited by 0% (0-1%) after placebo, and 70% (59-74%),
      81% (76-85%), 90% (86-93%), and 93% (90-96%) after the 4 increasing draflazine
      dosages, respectively (P < .05 for each draflazine dosage versus placebo). These
      results indicate that endogenously released adenosine may play a role in the
      regulation of ventilation.

PMID- 7650224
TI  - Novel oral medication delivery system for famotidine.
AB  - A famotidine wafer that rapidly disperses on the tongue without water is a novel
      alternative to other histamine2 (H2)-antagonist dosage forms. Benefits associated
      with such a dosage form include convenience and potentially improved compliance
      for patients who dislike or have difficulty taking tablets and capsules. This
      report describes the research of three studies on the famotidine wafer dosage
      form. In the first trial, the bioequivalence and tolerability of the new 40-mg
      famotidine wafer and the marketed 40-mg famotidine tablet were studied in a 2
      period crossover study (n = 18). The two formulations were bioequivalent as
      assessed by area under the plasma concentration versus time curve and maximum
      plasma concentration of famotidine. The plasma concentration of famotidine
      associated with 50% inhibition of pentagastrin stimulated gastric acid secretion
      (EC50; 10 ng/mL) was attained on average within 0.5 hours post-dose for the wafer
      and tablet. In a second trial, the tolerability of the famotidine 20-mg and 40-mg
      wafers or placebo given twice daily (bid) for 14 days were evaluated (n = 192).
      Both wafer strengths were well and equally tolerated. In a third trial of 450
      subjects, the 40-mg wafer was preferred over tablets by 75% of the subjects, when
      they were asked to consider the method of administration and flavor. When used as
      an alternative to tablets and other conventional dosage forms, the wafers have
      the potential therapeutic benefit of improved compliance. It is concluded that
      similar systemic exposure, excellent tolerability, palatability, and preference
      make the famotidine wafer a clinically acceptable and convenient dosage from for
      patients on H2-antagonist therapy.

PMID- 7650225
TI  - Disposition of phenylbutyrate and its metabolites, phenylacetate and
      phenylacetylglutamine.
AB  - Phenylacetate, an inducer of tumor cytostasis and differentiation, shows promise
      as a relatively nontoxic antineoplastic agent. Phenylacetate, however, has an
      unpleasant odor that might limit patient acceptability. Phenylbutyrate, an
      odorless compound that also has activity in tumor models, is known to undergo
      rapid conversion to phenylacetate by beta-oxidation in vivo. This phase I study
      examined the pharmacokinetics of phenylbutyrate and characterized the disposition
      of the two metabolites, phenylacetate and phenylacetylglutamine. Fourteen
      patients with cancer (aged 51.8 +/- 13.8 years) received a 30-minute infusion of
      phenylbutyrate at 3 dose levels (600, 1200, and 2000 mg/m2). Serial blood samples
      and 24-hour urine collections were obtained. Samples were assayed by high
      performance liquid chromatography. A model to simultaneously describe the
      pharmacokinetics of all three compounds was developed using ADAPT II. Data were
      modeled as molar equivalents. The model fit the data well as shown by mean (+/-
      SD) coefficients of determination (r2) for phenylbutyrate, phenylacetate, and
      phenylacetylglutamine, which were 0.96 +/- 0.07, 0.88 +/- 0.10, and 0.92 +/-
      0.06, respectively. The intrapatient coefficient of variation percentage (CV%)
      around the parameter estimates were small (range 7.2-33.5%). Phenylbutyrate
      achieved peak concentrations in the range of in vitro tumor activity (500-2000
      mumol/L) and exhibited saturable elimination (Km = 34.1 +/- 18.1 micrograms/mL
      and Vmax = 18.1 +/- 18 mg/h/kg). Metabolism was rapid; the times to maximum
      concentration for phenylacetate and phenylacetylglutamine were 1 and 2 hours,
      respectively. The conversion of phenylbutyrate to phenylacetate was extensive (80
      +/- 12.6%), but serum concentrations of phenylacetate were low owing to rapid,
      subsequent conversion to phenylacetylglutamine.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7650226
TI  - The effect of dosage release formulations on the pharmacokinetics of propranolol
      stereoisomers in humans.
AB  - Recent studies in dogs have suggested that the disposition of S- and R
      propranolol may depend on the input rate of drug delivered to the liver.
      Therefore, this study was designed to determine whether differences in the
      disposition of S- and R-propranolol occur in humans when altering the input rate
      of propranolol by giving different dosage forms of the drug. Twelve healthy
      subjects were enrolled in a single-dose, 4-way crossover pharmacokinetic study in
      which racemic propranolol was given according to 1 of 4 treatments: one 80-mg
      immediate-release (IR) tablet, phase A; two 80-mg IR tablets, phase B; a 160-mg
      controlled-release capsule, phase C; or a 10-mg IV bolus, phase D. The results
      showed no significant differences in the ratios of S/R-propranolol for AUC,
      clearance, or overall mean concentration among the oral dosage groups.
      Significant differences in these parameters including Cmax S/R ratio were seen
      between the oral phases and the IV phase. These differences appear to be related
      more to the route of administration than to the low input rate. However, at high
      concentrations there may be input-rate alteration in S/R ratios. Specifically,
      for phase B, which had the highest Cmax concentrations, the Cmax S/R ratio was
      significantly lower than the other oral dosage groups A and C (Cmax S/R ratios:
      1.44 versus 1.54 and 1.54, respectively; P < .05).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7650227
TI  - Pharmacokinetics of bepridil and two of its metabolites in patients with end
      stage renal disease.
AB  - The pharmacokinetics of bepridil and 2 of its major metabolites (McN-A-2600 and
      McN-6303) were studied in 6 patients with end-stage renal disease (ESRD) before
      and after hemodialysis. Patients underwent dialysis 1 day after a single oral 200
      mg dose of bepridil hydrochloride; blood was sampled for up to 7 days. The mean
      (+/- SD) peak plasma concentration, time of peak concentration, and area under
      the plasma concentration-time curve (0-168 hours) for each agent were as follows:
      bepridil, 806 +/- 321 ng/mL, 2.6 +/- 1.6 hours, 4.87 +/- 1.21 micrograms.h/mL;
      McN-A-2600, 57 +/- 16 ng/mL, 4.2 +/- 2.0 hours, 0.53 +/- 0.29 microgram.h/mL; McN
      6303, 284 +/- 120 ng/mL, 4.7 +/- 1.5 hours, 4.06 +/- 1.11 micrograms.h/mL. The
      bepridil area under the curve corrected for dose was similar to that in healthy
      volunteers, suggesting that plasma clearance was unaffected by severe renal
      impairment. None of the compounds were removed by dialysis, and no rebound in
      plasma concentrations was observed after the end of dialysis. The disposition of
      bepridil appears to be unchanged in patients with ESRD; and is unaffected by
      hemodialysis. Thus, no dosage adjustment will be required for ESRD patients and
      those receiving hemodialysis with cuprophane filters.

PMID- 7650228
TI  - Disposition of misoprostol and its active metabolite in patients with normal and
      impaired renal function.
AB  - The disposition of misoprostol acid, the active metabolite of misoprostol, was
      studied in 48 subjects with various degrees of renal function after
      administration of a single 400 microgram oral dose of misoprostol. Subjects were
      assigned to one of four treatment groups: group 1, normal renal function with
      creatinine clearance (CLCR) 80-140 mL/min/1.73 m2; group 2, mild renal impairment
      with CLCR 50-79 mL/min/1.73 m2; group 3, moderate renal impairment with CLCR 20
      49 mL/min/1.73 m2 or group 4, end stage renal disease (ESRD) patients maintained
      on hemodialysis. The maximum plasma concentration (Cmax) and time to reach Cmax
      (tmax) for misoprostol acid tended to be larger in group 4 subjects; however, it
      failed to reach statistical significance. Although not statistically significant,
      in group 4 subjects the terminal half-life (t1/2) of misoprostol acid was almost
      twice as large (1.27 +/- 0.77 h) as in groups 1, 2, and 3 (0.70 +/- 0.72, 0.72 +/
      0.67, and 0.73 +/- 0.45 h, respectively). Misoprostol acid's total area under
      the plasma concentration curve (AUC0 infinity) was larger in group 4 subjects
      (1173.5 +/- 487.4 pg.h/mL) as compared with groups 1, 2, and 3 (421.4 +/- 263.1,
      418.9 +/- 114.5, and 377.0 +/- 145.2 pg.h/mL, respectively; P < .05). The
      apparent total body clearance (CL) of misoprostol acid was statistically
      significantly smaller in group 4 subjects (0.094 +/- 0.044 L/kg/min) as compared
      only with group 3 subjects (0.284 +/- 0.102 L/kg/min). The dose of misoprostol
      may need to be reduced in ESRD patients on prolonged hemodialysis to prevent
      unnecessary high plasma levels of misoprostol acid and to avoid possible dose
      related adverse effects.

PMID- 7650229
TI  - Comparative pharmacokinetics and bioavailability of nitroglycerin and its
      metabolites from Transderm-Nitro, Nitrodisc, and Nitro-Dur II systems using a
      stable-isotope technique.
AB  - The pharmacokinetics and bioavailability of nitroglycerin (GTN) and its
      metabolites, 1,2-glyceryl dinitrate (1,2-GDN) and 1,3-glyceryl dinitrate (1,3
      GDN), were compared after a single 14-hour application of Transderm-Nitro (Ciba
      Geigy, Summit, NJ), Nitrodisc (GD Searle, Chicago, IL), and Nitro-Dur II (Key
      Pharmaceuticals, Kenilworth, NJ) systems to 18 healthy male subjects on 3
      separate occasions. A 14-hour intravenous infusion of 15N-labeled GTN was given
      simultaneously to correct for changes in systemic clearance during the
      application of each system. Plasma concentrations of 15N-labeled GTN, unlabeled
      GTN, and their corresponding dinitrate metabolites were measured using a gas
      chromatography/mass spectrometry method. Results showed that the plasma
      concentration profiles of nitroglycerin and its metabolites for the three systems
      were similar during and after system removal. Mean (SD) total amounts (AUCp x
      CLiv) of GTN transdermally available after adjustment for 15N-labeled GTN
      clearance were 5.3 (2.1), 5.3 (2.0), and 5.4 (2.6) mg for Transderm-Nitro,
      Nitrodisc, and Nitro-Dur II, respectively. Mean (SD) AUC values for 1,2-GDN were
      44.6 (15.8), 44.3 (16.1), and 42.8 (19.3) ng.h/mL for the 3 systems.
      Corresponding AUC values for 1,3-GDN were 9.3 (2.9), 9.7 (2.9), and 8.7 (3.0)
      ng.h/mL. Statistical analysis of the log-transformed data based on 90%
      conventional confidence interval showed that all 3 systems delivered equivalent
      amounts of nitroglycerin into the systemic circulation. The AUC ratios for 1,3
      GDN to GTN, but not 1,2-GDN to GTN, were statistically different for the
      intravenous and transdermal routes during all 3 system applications, indicating
      that the formation and metabolism of 1,3-GDN was dependent on route of
      administration.

PMID- 7650230
TI  - Single- and multiple-dose pharmacokinetics of dezocine in patients with acute or
      chronic pain.
AB  - The pharmacokinetic properties of dezocine were examined in 15 patients with
      acute or chronic pain. In 3 groups of 5 patients each, serum levels were
      determined at various intervals after single intravenous doses of 5, 10, and 20
      mg. After these single doses, dezocine was very rapidly distributed (mean t1/2
      alpha less than 2 minutes), and then rather rapidly eliminated (mean t1/2 beta
      about 4 hours); the apparent volume of distribution was large (mean Vz beta about
      6 L/kg) as was the total clearance (mean CL about 1.5 L/h/kg). In 2 groups of 5
      patients each, serum levels were determined after the first and third of 3
      intravenous doses of 5 or 20 mg given at 3-hour intervals. The pharmacokinetic
      parameters after these multiple doses were consistent with those after the single
      doses. Although some observations were suggestive, there was no unequivocal
      evidence that the pharmacokinetics were dose-related. In 7 serum samples
      containing dezocine at concentrations ranging from 12.8 to 522 ng/mL, the mean
      (+/- SE) proportion of dezocine bound to protein was 91.6 +/- 0.8%.

PMID- 7650231
TI  - The pharmacokinetics of venlafaxine when given in a twice-daily regimen.
AB  - The comparative bioavailability of the novel antidepressant venlafaxine and its
      pharmacologically active metabolite O-desmethylvenlafaxine was assessed when
      venlafaxine was given orally twice daily (75 mg bid) or 3 times daily (50 mg
      tid). Eighteen healthy subjects participated in an open-label, randomized, two
      period, crossover study lasting 12 days. Each subject was randomly assigned to
      take venlafaxine according to a bid or a tid regimen through day 8 and was
      crossed over to the other regimen on days 9 to 12. The daily dose was titrated up
      to 150 mg/d and was held constant on days 5 to 12. Plasma samples for
      quantitation of venlafaxine and O-desmethylvenlafaxine were obtained during a 24
      hour steady-state interval on days 8 and 12. Analysis of variance showed no
      significant differences between the two venlafaxine regimens for peak
      concentration (Cmax), area under the curve during 24 hours (AUC0-24), trough
      concentration, or fluctuation ratio for venlafaxine or O-desmethylvenlafaxine in
      plasma. The bioequivalence ratios for Cmax and AUC0-24 of both compounds were
      calculated to compare the bid regimen and the tid regimen. The mean value for
      each of the 4 ratios was between 96 and 100%, and the 90% confidence limits
      around each ratio were within 90 to 110%. These results indicate that dividing a
      daily 150-mg venlafaxine dose into 2 or 3 doses provides equivalent total
      exposure and peak plasma concentrations of venlafaxine and O
      desmethylvenlafaxine, its active metabolite. Therefore, based on pharmacokinetic
      considerations, it appears that the same daily dose of venlafaxine can be given
      in either two or three divided doses without compromising efficacy.

PMID- 7650232
TI  - Pharmacokinetic and pharmacodynamic evaluation of the potential drug interaction
      between venlafaxine and diazepam.
AB  - To assess possible pharmacokinetic and pharmacodynamic interactions between the
      antidepressant venlafaxine and diazepam, a randomized, two-period, crossover
      study was conducted in 18 men. Multiple-dose venlafaxine (50 mg every 8 hours) or
      placebo (double-blind) was given for 10 days; on day 4 a single placebo dose
      (same appearance as diazepam capsule, single-blind) was given; and on day 5 a
      single dose of diazepam (10 mg) was given. Pharmacokinetic data indicated that
      diazepam had no significant effect on venlafaxine or O-desmethylvenlafaxine
      disposition. Diazepam pharmacokinetics were minimally changed in the presence of
      venlafaxine. Diazepam oral clearance (CL/f) increased slightly (24 +/- 8 versus
      26 +/- 6 mL/h/kg; P = .007), volume of distribution (Vz/f) increased (0.85 +/-
      0.28 versus 0.99 +/- 0.34 L/kg; P = .02), and AUC decreased (5973 +/- 2304 versus
      5008 +/- 1354 ng.h/mL; P = .02). Venlafaxine did not alter desmethyldiazepam
      pharmacokinetics. Pharmacodynamic data showed a statistically significant
      diazepam-venlafaxine interaction for only one of the eight psychometric tests
      given. Critical flicker fusion slightly decreased (P = .01) between placebo
      diazepam (37.85 +/- 3.28 Hz) and venlafaxine-diazepam (37.09 +/- 4.13 Hz)
      treatments. The observed pharmacokinetic and pharmacodynamic interactions between
      diazepam and venlafaxine were small and probably clinically insignificant.

PMID- 7650233
TI  - Does tetanus immune globulin interfere with the immune response to simultaneous
      administration of tetanus-diphtheria vaccine? A comparative clinical trial in
      adults.
AB  - In the management of wounds, sometimes it is recommended to give an adult-type
      tetanus-diphtheria (Td) vaccine dose plus tetanus immune globulin (TIG). Sixty
      and 59 healthy young adults previously immunized against tetanus (T) and
      diphtheria (D) were randomized to receive intramuscularly either Td vaccine alone
      (group 1) or Td vaccine plus 500 IU of TIG (group 2) simultaneously. Antitoxin
      response was assessed after 4 weeks and 4 months. Circulating antibodies were
      measured by enzyme-linked immunosorbent assay (ELISA). The cutoff of these tests
      was 0.1 IU/mL. Titers of 0.1 IU/mL or greater were considered protective. For
      geometric mean titers (GMT), antibody titers below the cutoff of the assay were
      given, arbitrarily, 0.05 IU/mL. At 4 weeks, 98% or more of the subjects in group
      1 had circulating T and D antitoxin levels of 0.1 IU/mL or higher; in group 2,
      95% and 90% of the subjects had titers above this limit for T and D,
      respectively. At 4 months, these percentages were 98% and 95% for T antitoxin
      levels in groups 1 and 2, respectively; whereas 96% and 88% of the subjects in
      groups 1 and 2 had D antitoxin levels of 0.1 IU/mL or higher, respectively.
      Significantly (P < .05) higher GMTs were seen at the 4-week assessment (but not
      at 4 months) in group 1, as compared with group 2, in both T and D antitoxin
      levels (9.91 IU/mL versus 5.60 IU/mL for T antitoxin, and 2.86 IU/mL versus 1.45
      IU/mL for D antitoxin). This finding resulted from those participants with low (<
      0.1 IU/mL) prevaccination antibody titers.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7650234
TI  - The influence of adrenalin on the pharmacokinetics of interpleurally administered
      lidocaine in patients with pancreatic neoplasia.
AB  - The influence of adrenalin on the pharmacokinetics of lidocaine given
      interpleurally to 10 patients with pancreatic neoplasia was studied. Five
      patients received an interpleural dose of lidocaine (200 mg; control group), and
      5 patients received an interpleural dose of lidocaine (200 mg) plus adrenalin
      (1:200,000). Plasma and cerebrospinal fluid (CSF) levels of lidocaine were
      measured before and at specified times (up to 8 hours) after the dose. The
      analytical technique was radioimmunoassay; and plasma and CSF data were assessed
      using noncompartmental analysis. The drug was quickly absorbed into the plasma in
      the control group (Cmax = 2.76 +/- 0.10 microgram/mL at 0.33 +/- 0.14 hours after
      administration); whereas drug access to CSF was decreased and occurred slowly
      (Cmax = 0.32 +/- 0.07 microgram/mL at 1.66 +/- 1.35 hours). The drug was
      eliminated more quickly from plasma than from CSF, with half-lives of 1.71 +/-
      0.43 hours and 3.86 +/- 1.27 hours, respectively. The simultaneous administration
      of adrenalin delayed absorption (tmax = 0.91 +/- 0.52 hours). The drug
      elimination half-lives in plasma and CSF of this group increased to 3.22 +/- 1.22
      hours and 8.71 +/- 3.28 hours, respectively. The duration of the analgesia,
      evaluated as the time until the patient needed another dose, increased from 8.2
      +/- 1.5 hours in the control group to 9.7 +/- 1.3 hours in the group that
      received adrenalin. From these results the levels that would be reached on a
      multiple-dose regimen (D = 200 mg, tau = 8 hours) were predicted.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7650235
TI  - Lack of pharmacokinetic interaction between butorphanol tartrate nasal spray and
      sumatriptan succinate.
AB  - The pharmacokinetics of butorphanol tartrate given in a nasal spray with and
      without the co-administration of sumatriptan succinate were studied in 24 healthy
      men and women. In this crossover design study, all subjects received 2
      treatments: a single 1-mg dose of butorphanol nasal spray and a 1-mg dose of
      butorphanol nasal spray plus a single 6-mg subcutaneous (SC) dose of sumatriptan.
      There was a two-week washout period between sessions. Serial blood samples were
      collected and plasma samples analyzed using validated radioimmunoassay and high
      performance liquid chromatography/electrochemical procedures to determine the
      concentrations of unchanged butorphanol and sumatriptan, respectively. There were
      no statistically significant differences for butorphanol between the 2 treatments
      on any of the following pharmacokinetic parameters: Cmax, tmax, AUC, t1/2, CL/f,
      and Vz/f. Similarly, the pharmacokinetic parameters obtained for sumatriptan
      (given with butorphanol nasal spray) were comparable with the literature values
      obtained for a single 6-mg SC dose of sumatriptan. These data show a lack of
      pharmacokinetic interaction between butorphanol nasal spray and sumatriptan.
      Butorphanol nasal spray and sumatriptan were well tolerated. The adverse
      experience profiles of butorphanol nasal spray were comparable between the
      treatments, with and without sumatriptan. It can be concluded that regimens of
      butorphanol nasal spray and sumatriptan need not be changed for either
      pharmacokinetic or safety considerations when the two compounds are co
      administered in treating acute migraine attacks.

PMID- 7650236
TI  - Cutaneous ultrastructural features of the flaky skin (fsn) mouse mutation.
AB  - An autosomal recessive genetic disease with clinical and histopathological skin
      features resembling human psoriasis vulgaris occurs naturally in flaky skin mice
      (fsn/fsn). Affected mice are normal at birth, except for a hypochromic anemia.
      Subsequently, they develop hyperkeratotic plaques and acanthosis with elongation
      of rete ridges. Scanning electron microscopic examination revealed a greatly
      thickened epidermis, a sparsity of hairs and scale accumulations on the epidermal
      surface. Hair shafts had conspicuous pits, striations, and exophytic protrusions.
      Nails were bent at a 90 degrees angle with surface irregularities and
      accumulations of scale at the nail base. Transmission electron microscopic
      examination showed increased epidermal thickness, mitochondrial aberrations, and
      intraepidermal invasion by neutrophils. Keratohyalin abnormalities were detected
      using immunocytochemical staining for profilaggrin. At the dermal-epidermal
      junction, numerous macrophages and mast cells were seen in close proximity to
      focal dissolutions of the basement membrane. A high density of collagen fibers
      and cellular infiltrates were evident in the papillary dermis. This constellation
      of ultrastructural aberrations is typically found in psoriasis vulgaris and
      supports the theory that the flaky skin mouse mutation is a naturally occurring
      analog to one variety of human psoriasis vulgaris.

PMID- 7650237
TI  - Proliferating activity of the hair follicular melanocytes at the early and anagen
      III stages in the hair growth cycle: detection by immunocytochemistry for
      bromodeoxyuridine combined with DOPA reaction cytochemistry.
AB  - In order to demonstrate the existence of proliferating activity in hair
      follicular melanocytes during the early and anagen III stages,
      immunocytochemistry for bromodeoxyuridine (BrdU) incorporated in the nuclei of
      the melanocytes for 1 hr was undertaken at the light and electron microscopic
      levels in combination with DOPA reaction cytochemistry. Light microscopically,
      about 30% of the nuclei of the DOPA reaction positive melanocytes at the anagen
      III stage of the hair growth cycle were labeled by anti-BrdU antibody. These
      melanocytes were observed in about one hundred hair follicles. Electron
      microscopically, the nuclei of a few undifferentiated melanocytes at the anagen
      II stage were labeled by anti-BrdU antibody-affiliated secondary antibody-gold
      particles. At the anagen III stage, localization of the immunogold particles in
      the DNA replication domains of the nuclei of the undifferentiated and
      redifferentiating melanocytes covered the patterns of the early, middle, and late
      S-phase. These findings suggest that the hair follicular melanocytes begin
      proliferation at the anagen II stage and that the melanocytes proliferate
      actively at the anagen III stage to repopulate the hair matrix during subsequent
      hair growth.

PMID- 7650238
TI  - Immunoglobulin gene analysis of cutaneous pseudolymphoma by polymerase chain
      reaction.
AB  - Polymerase chain reaction (PCR) was used to amplify the V-D-J region of the
      immunoglobulin heavy chain gene from DNA extracted from the formalin fixed,
      paraffin embedded skin of 3 cases of pseudolymphoma. The products were
      electrophoresed and observed under ultraviolet light after ethidium bromide
      staining. Specimens of two cases showed smears of polyclonal amplified DNA. The
      specimen of one case (Case 3), however, showed a single band with a smear. The
      presence of monoclonality in B lymphocyte populations may suggest the possibility
      of low grade malignancy of pseudolymphoma or transformation to malignant lymphoma
      in the future.

PMID- 7650239
TI  - Immunoglobulins specific to mosquito salivary gland proteins in the sera of
      persons with common or hypersensitive reactions to mosquito bites.
AB  - Using the immunoblot technique, we analyzed the quality and quantity of IgG,
      IgG4, and IgE specific to mosquito salivary gland (hereafter abbreviate as SG)
      components of Aedes albopictus in the sera of volunteers with common reactions
      and of 3 patients with severe reactions. In the volunteers with delayed reactions
      only or with both delayed and immediate reactions, IgG against SG components of
      A. albopictus formed several faint or moderately stained bands. Those with
      immediate reactions showed several intense bands and many other weak bands. In
      volunteers, who had been bitten by Aedes sp. frequently but had no skin reaction,
      and in severe cases, many intense IgG bands were observed. IgG4 bound to SG
      components were found in the sera of the common reaction group at the levels of
      24 and 48 kD, but, in one severe case, no bands were observed, although the total
      IgG was very high. IgE levels specific to SG components were much higher in
      severe cases than in the volunteers. These results indicate that high titers of
      specific IgG and IgE and lack of IgG4 for particular components of SG may lead to
      severe allergic reactions in severe cases. Immunoblotting analysis of the
      antibodies also verified the possibility of developing in vitro tests to identify
      causative species of the mosquito for severe cases.

PMID- 7650240
TI  - Detection of epidermal cellular DNA content and its clinical significance in
      psoriasis vulgaris.
AB  - Epidermal cellular DNA content was detected by flow cytometry on 14 samples of
      normal skin and both lesional and nonlesional areas of 36 patients with psoriasis
      vulgaris. The results showed that the proliferative activity of epidermal cells
      increased in nonlesions and even more in lesions of patients from the levels in
      normal skin. These differences were significant (p < 0.05). Clinical features and
      histopathological changes were observed, and self comparisons of 6 patients
      before and after treatment were also done. The clinical significance of these
      changes was discussed.

PMID- 7650241
TI  - Adolescence mycosis fungoides: an unusual presentation with hypopigmentation.
AB  - Mycosis fungoides (M.F.) is a rare cutaneous malignancy of childhood and
      adolescence. The disease commonly presents with the classic sequence of
      erythematous patches and plaques. Hypopigmentation as the presenting symptom is
      distinctly rare. This is the 9th case report of M.F. presenting with
      hypopigmentation in a patient under 20 years of age. The disease was only
      partially controlled with PUVA therapy, necessitating nitrogen mustard treatment.

PMID- 7650242
TI  - A case of AIDS manifesting pruritic papular eruptions and psoriasiform lesions:
      an immunohistochemical study of the lesional dermal infiltrates.
AB  - A 63-year-old man was referred to our department on September 14, 1992, because
      of multiple red papules with severe itching. Pruritic papular eruption (PPE) in a
      human immunodeficiency virus (HIV)-infected patient was diagnosed based on the
      histological findings, the reduction in CD4, and positive results for HIV
      antibody. In September of 1993, papules and erythematous plaques with scales
      appeared on both the palms and soles. The erythema was pruritic and spread
      gradually to the extremities and trunk. These plaques with erythema and scales
      are similar to those of the psoriatic lesions seen in Reiter's syndrome, although
      the HLA typing was not B27. Immunohistopathological findings of the papules of
      PPE and plaques of psoriasiform lesions showed that perivascularly infiltrated
      cells in the dermis were mostly lymphocytes. The lymphocytes in PPE were positive
      for CD45 and negative for CD3, CD43, and CD45RO, but the lymphocytes in
      psoriasiform lesions were positive for CD45, CD3, and CD43. Moreover, 20-30% of
      these lymphocytes were also intensely positive for CD45RO. These observations
      were similar to those obtained in the lesional skin of HIV-negative psoriasis,
      suggesting that there were no significant immunohistopathological differences in
      the abnormality of local cellular immunity related to the formation of
      psoriasiform lesions in HIV-negative psoriasis and HIV-positive psoriasis.

PMID- 7650243
TI  - Generalized lichen nitidus appearing subsequent to lichen planus.
AB  - A 27-year-old man was seen with multiple, small, shiny papules on his shoulders,
      upper arms, and trunk, and hyperpigmented violaceous plaques on his feet. The
      former was diagnosed as generalized lichen nitidus and the latter, as lichen
      planus. It is not likely that the coexistence of the two diseases in this patient
      is a fortuitous one, since generalized lichen nitidus is a very rare condition.
      The association of lichen nitidus and lichen planus suggests that lichen nitidus
      is closely related to lichen planus and that the two diseases may be different
      manifestations of essentially the same pathogenetic process.

PMID- 7650244
TI  - A case of steatocystoma multiplex with prominent cysts on the scalp treated
      successfully using a simple surgical technique.
AB  - The case described is a 35-year-old male with multiple cysts on the upper half of
      his body. This patient was diagnosed as having steatocystoma multiplex, based on
      clinical and histological findings. The lesions consisted of widespread and
      unusually prominent cysts, which were removed by a simple surgical technique
      using a dermatological trepan and artery forceps. We provide here a detailed
      description of the surgical procedures employed.

PMID- 7650245
TI  - Primary cutaneous Ki-1+ anaplastic large cell lymphoma: a morphologic,
      immunohistochemical and genetic study of an indolent case.
AB  - A 59-year-old woman with a large nodular ulcerative lesion on her neck was
      presented. She had a 3 year history of recurrent cutaneous nodules which
      spontaneously regressed before regional lymphadenopathies appeared. She has
      followed an indolent clinical course for seven years after the first overt
      lymphadenopathies appeared. Histological findings were compatible with anaplastic
      large cell lymphoma (ALCL). The tumor cells strongly expressed Ki-1 (CD30), HLA
      DR, IL-2 receptor (CD25) and leukocyte common antigen. These findings led to the
      diagnosis of primary cutaneous Ki-1+ ALCL. Although the majority of the tumor
      cells did not express T-cell related antigens, the detection of monoclonal TCR
      gene rearrangement clearly established the T-cell lineage nature.

PMID- 7650246
TI  - A case of multiple eccrine porocarcinoma with stepping-stone distribution on the
      foot.
AB  - An 89-year-old woman had three tumors of several years' duration in a stepping
      stone distribution on the dorsum of her right foot. The two larger ones were
      diagnosed histologically as eccrine porocarcinomas, and the smallest of the three
      shared many clinical similarities with them. Eccrine porocarcinoma is a rare
      malignant tumor. We describe this peculiar case in which three tumors developed
      in the same region and discuss how they might have occurred. It is most likely
      that the three tumors of this case originated from nevoid tumors, and that the
      individual lesions exhibited malignant changes.

PMID- 7650247
TI  - Coexistence of subepidermal calcified nodule and keratosis punctata in a patient
      with hyperhidrosis.
AB  - A 47-year-old female with hyperhidrosis developed multiple subepidermal calcified
      nodules and keratosis punctata on her palms. Although calcification was not
      detected on eccrine sweat glands around the calcified mass by histologic
      examination, it was supposed that the eccrine sweat glands may have played a role
      in inducing these two lesions in our case.

PMID- 7650248
TI  - Appearance of oral erosive lichen planus during interferon alfa-2a therapy for
      chronic active hepatitis C.

PMID- 7650250
TI  - Right heart catheterization at bedside: a note of cautious optimism.

PMID- 7650249
TI  - Right heart catheterization at bedside: a critical view.

PMID- 7650251
TI  - Sepsis, SIRS and infection.

PMID- 7650252
TI  - Systemic inflammatory response syndrome, sepsis, severe sepsis and septic shock:
      incidence, morbidities and outcomes in surgical ICU patients.
AB  - OBJECTIVES: To determine the incidence of systemic inflammatory response syndrome
      (SIRS), sepsis and severe sepsis in surgical ICU patients and define patient
      characteristics associated with their acquisition and outcome. DESIGN: One-month
      prospective study of critically ill patients with a 28 day in-hospital follow up.
      SETTING: Surgical intensive care unit (SICU) at a tertiary care institution.
      METHODS: All patients (n = 170) admitted to the SICU between April 1 and April
      30, 1992 were prospectively followed for 28 days. Daily surveillance was
      performed by two dedicated, specifically-trained research nurses. Medical and
      nursing chart reviews were performed, and follow up information at six and twelve
      months was obtained. RESULTS: The in-hospital surveillance represented 2246
      patient-days, including 658 ICU patient-days. Overall, 158 patients (93%) had
      SIRS for an incidence of 542 episodes/1000 patients-days. The incidence of SIRS
      in the ICU was even higher (840 episodes/1000 patients-days). A total of 83
      patients (49%) had sepsis; among them 28 developed severe sepsis. Importantly, 13
      patients had severe sepsis after discharge from the ICU. Patient groups were
      comparable with respect to age, sex ratio, and type of surgery performed. Apache
      II score on admission to the ICU and ASA score at time of surgery were
      significantly higher (p < 0.05) only for patients who subsequently developed
      severe sepsis. The crude mortality at 28 days was 8.2% (14/170); it markedly
      differed among patient groups: 6% for those with SIRS vs. 35% for patients with
      severe sepsis. Patients with sepsis and severe sepsis had a longer mean length of
      ICU stay (2.1 +/- 0.2 and 7.5 +/- 1.5, respectively) than those with SIRS (1.45
      +/- 0.1) or control patients (1.16 +/- 0.1). Total length of hospital stay also
      markedly differed among groups (35 +/- 9 (severe sepsis), 24 +/- 2 (sepsis), 11
      +/- 0.8 (SIRS), and 9 +/- 0.1 (controls, respectively). CONCLUSIONS: Almost
      everyone in the SICU had SIRS. Therefore, because of its poor specificity, SIRS
      was not helpful predicting severe sepsis and septic shock. Patients who developed
      sepsis or severe sepsis had higher crude mortality and length of stay than those
      who did not. Studies designed to identify those who develop complications of SIRS
      would be very useful.

PMID- 7650254
TI  - Breathing pattern and gas exchange in emergency and elective abdominal surgical
      patients.
AB  - OBJECTIVE: To evaluate the effects of intra-abdominal surgical emergency on
      breathing pattern and gas exchange and compare it with the changes induced by
      elective abdominal surgery. DESIGN: Prospective clinical study. SETTING:
      Abdominal surgical departments in a university hospital. PATIENTS: Patients
      operated for intra-abdominal emergency (n = 10, EAS), elective upper abdominal (n
      = 19, UAS). MEASUREMENTS AND RESULTS: Breathing pattern and gas exchange were
      measured with a respiratory inductive plethysmograph and a gas exchange monitor.
      EAS patients had pre-operatively a classical rapid shallow breathing pattern and
      increased ventilatory demand due to increased energy expenditure. The operation
      improved the breathing to normal pattern (frequency, 26 +/- 5/min and 17 +/-
      3/min, p < 0.01; tidal volume, 439 +/- 128 ml and 541 +/- 165 ml, NS., before and
      after surgery, respectively). Sighing was absent before and after EAS and
      strictly reduced after elective surgery (p < 0.01 for UAS). The operation
      restricted the abdominal-diaphragmatic breathing movement which was reflected as
      increased contribution of the rib cage to VT (%RC: from 37% +/- 15 to 57% +/- 15
      for UAS p < 0.001; from 47% +/- 16 to 61% +/- 14 for EAS NS.). After EAS and UAS
      hypoxemia was common (p < 0.001) with frequent radiological pathology. We
      conclude that intra-abdominal surgical emergencies increase the ventilatory
      demand and challenge the respiratory system to marked adaptive changes both pre-
      and post-operatively.

PMID- 7650253
TI  - Different ventilatory approaches to keep the lung open.
AB  - OBJECTIVES: To study the ability of different ventilatory approaches to keep the
      lung open. DESIGN: Different ventilatory patterns were applied in surfactant
      deficient lungs with PEEP set to achieve pre-lavage PaO2. SETTING: Experimental
      laboratory of a University Department of Anaesthesiology and Intensive Care.
      ANIMALS: 15 anaesthetised piglets. INTERVENTIONS: One volume-controlled mode (L
      IPPV201:1.5) and two pressure-controlled modes at 20 breaths per minute (bpm) and
      I:E ratios of 2:1 and 1.5:1 (L-PRVC202:1 and L-PRVC201.5:1), and two pressure
      controlled modes at 60 bpm and I:E of 1:1 and 1:1.5 (L-PRVC601:1 and L
      PRVC601:1.5) were investigated. The pressure-controlled modes were applied using
      "Pressure-Regulated Volume-Controlled Ventilation" (PRVC). MEASUREMENTS AND
      RESULTS: Gas exchange, airway pressures, hemodynamics, FRC and intrathoracic
      fluid volumes were measured. Gas exchange was the same for all modes. FRC was 30%
      higher with all post-lavage settings. By reducing inspiratory time MPAW decreased
      from 25 cmH2O by 3 cmH2O with L-PRVC201.5:1 and L-PRVC601:1.5. End-inspiratory
      airway pressure was 29 cmH2O with L-PRVC201.5:1 and 40 cmH2O with L-IPPV201:1.5,
      while the other modes displayed intermediate values. End-inspiratory lung volume
      was 65 ml/kg with L-IPPV201:1.5, but it was reduced to 50 and 49 ml/kg with L
      PRVC601:1 and L-PRVC601:1.5. Compliance was 16 and 18 ml/cmH2O with L-PRVC202:1
      and L-PRVC201.5:1, while it was lower with L-IPPV201:1.5, L-PRVC601:1 and L
      PRVC601:1.5. Oxygen delivery was maintained at pre-lavage level with L
      PRVC201.5:1 (657 ml/min.m2), the other modes displayed reduced oxygen delivery
      compared with pre-lavage. CONCLUSION: Neither the rapid frequency modes nor the
      low frequency volume-controlled mode kept the surfactant deficient lungs open.
      Pressure-controlled inverse ratio ventilation (20 bpm) kept the lungs open at
      reduced end-inspiratory airway pressures and hence reduced risk of barotrauma.
      Reducing I:E ratio in this latter modality from 2:1 to 1.5:1 further improved
      oxygen delivery.

PMID- 7650256
TI  - Thyroid and thymic endocrine function and survival in severely traumatized
      patients with or without head injury.
AB  - OBJECTIVE: Functional links among the brain, endocrine and immune system have
      been described previously. An impairment of both immunological defence mechanisms
      and thyroid hormone turnover was present in trauma conditions. An investigation
      on the relevance of thymulin and thyroid hormones in multiple trauma patients
      with or without head injury has been performed. The role of these hormones as
      predictive factors for patients outcome was also evaluated. DESIGN: Plasma
      thymulin levels and plasma thyroid hormone concentrations were tested in multiple
      trauma patients 24 h after admission to the Intensive Care Unit (ICU) and again
      after 5 and 10 days. SETTING: Department of Immunology Ctr. INRCA, IInd ICU, S.
      Matteo Hospital Pavia and ICU "Umberto I" Hospital, Ancona. PATIENTS: 45 patients
      were evaluated including 14 multiple trauma patients without head injury and 31
      multiple trauma patients with head injury at various level of coma, graded
      according to the Glascow Coma Score (GCS). INTERVENTIONS: Routine protocol
      interventions were performed in all head injured patients. MEASUREMENTS AND
      RESULTS: Thymulin and triiodothyronine (T3) levels were reduced, and reverse
      triiodothyronine (rT3) increased in all traumatized patients, but multiple trauma
      patients with head injury and GCS < or = 5 had the lowest levels of thymulin and
      T3 and the highest levels of rT3. No difference in plasma thyroxine (T4) and
      thyrotropin (TSH) levels was observed among injured patients. The analysis of
      predictive factors for the outcome has assigned to thymulin the highest score
      (29.6%) compared with the score for T3 (19.3%) and rT3 (26.3%). The total
      relative risk (delta %) calculated on the basis of T3 or rT3 rises significantly
      when thymulin relative risk is added. CONCLUSIONS: Thymulin is markedly reduced
      in multiple trauma patients with head injury and it represents a predictive
      factor for the outcome better than the one deriving from the single measurements
      restricted to thyroid hormones.

PMID- 7650255
TI  - Smoke inhalation causes a delayed increase in airway blood flow to primarily
      uninjured lung areas.
AB  - OBJECTIVE: Single lung inhalation injury causes tissue damage to the
      contralateral lung. We therefore examined airway blood flow after smoke
      inhalation in chronic instrumented sheep to get further information about the
      underlying pathophysiology. DESIGN/PATIENTS: The right lung and lower trachea of
      5 animals were smoke-exposed, while their left lung was air-insufflated using a
      split ventilation technique. Three animals, where both lungs were only air
      insufflated, served as controls. Blood flow to the airway was measured using a
      labeled microsphere technique. All animals were studied for 24 h following smoke
      inhalation. Then they were sacrificed and their tissues harvested. RESULTS: The
      airway blood flow to the smoke-exposed lung was elevated 11-fold immediately
      after inhalation injury. The bronchial blood flow to the air insufflated lung
      became significantly elevated 24 h post-smoke, although to a lesser extent. The
      control animals did not show any changes of bronchial blood flow during the
      observation time. CONCLUSIONS: Damage to one lung can lead to pathophysiologic
      changes in the contralateral lung. This response appears to be mediated by
      hematogenous factors.

PMID- 7650257
TI  - The use of propofol for sedation of critically ill patients undergoing
      haemodiafiltration.
AB  - OBJECTIVE: To assess the requirement for propofol to provide sedation in
      critically ill patients in established renal failure during the commencement of
      haemodiafiltration. DESIGN: Prospective clinical study. SETTING: ICU, University
      Hospital. PATIENTS: 10 adult patients. All were mechanically ventilated, had
      acute oliguric renal failure which necessitated continuous veno-venous
      haemodiafiltration and were receiving a continuous intravenous infusion of
      propofol for sedation. Sedation was assessed using a scoring system.
      INTERVENTION: Veno-venous haemodiafiltration. MEASUREMENTS AND RESULTS:
      Connection of the extracorporeal circuit produced a reduction in plasma propofol
      concentration in 7 out of 9 patients (one sample misplaced) with subsequent
      awakening in 3 of these 7 patients. The commencement of haemodiafiltration itself
      did not significantly influence the requirement for propofol (8 out of 10
      patients). CONCLUSION: Haemodiafiltration does not substantially influence the
      requirement for propofol but the initial introduction of the extracorporeal
      circuit will reduce plasma concentrations in the majority of patients. This may
      be due to haemodilution alone or absorption of plasma albumin (with propofol)
      onto the membrane.

PMID- 7650258
TI  - Pharmacokinetics of single-dose intravenous amikacin in critically ill patients
      undergoing slow hemodialysis.
AB  - OBJECTIVE: The pharmacokinetics of amikacin were studied in patients undergoing
      slow hemodialysis (HD). DESIGN: Slow HD was performed at the dialysate flow rate
      of 30 ml/min. After a single intravenous dose of amikacin 5 mg/kg,
      pharmacokinetic variables were calculated by fitting individual concentration
      time curves to a two-compartment open model. PATIENTS: 6 critically ill patients
      with renal failure were entered into the study. RESULTS: The volume of
      distribution was 0.35 +/- 0.03 l/kg. Total body clearance was 35.1 +/- 2.3 ml/min
      with an elimination half-life of 10.5 h. During a 10.5 h session of slow HD, the
      serum amikacin concentration decreased from the peak level of 21.3 +/- 1.2 mg/l
      to 7.2 +/- 0.9 mg/l. CONCLUSION: Slow HD eliminate amikacin more efficiently than
      other types of slowly performed renal replacement therapy and had profound
      effects on the pharmacokinetics. Amikacin elimination by this approach should be
      taken into consideration for designing a dosage schedule during the treatment.

PMID- 7650260
TI  - Evaluation of severity scoring systems in ICUs--translation, conversion and
      definition ambiguities as a source of inter-observer variability in Apache II,
      SAPS and OSF.
AB  - OBJECTIVE: To explore translation, conversion and definition ambiguities, when
      using severity scoring systems in patients admitted to intensive care units
      (ICUs). DESIGN: A prospective study of the prognosis of acute renal failure in
      ICUs. SETTING: The study was conducted in 20 French ICUs. PATIENTS: 360 patients
      presenting with severe acute renal failure were studied during their ICU stay.
      MEASUREMENTS AND RESULTS: The inter-observer variability of Apache II (acute
      physiology and chronic health evaluation), SAPS (simplified acute physiology
      score), and OSF (organ-system failure) was considered. For Apache II, we explored
      the uncertainty of measurements arising from conversion into SI units, the
      rounding procedures used for the non-inclusive intervals defined for quantitative
      parameters such as age, mean arterial pressure (MAP) or serum creatinine, the
      absence of definition of acute renal failure (ARF) and its consequence on
      doubling serum creatinine values, and the absence of guidelines in the case of
      spontaneous ventilation when arterial blood gases (ABG) and forced inspiratory
      oxygen (FIO2) were not measured. The resulting variability was evaluated,
      calculating the lowest and the highest value of the scoring system for each
      patient. The mean difference by patient was greater than 1.5 (p < 0.0001). Other
      examples were presented and discussed for SAPS and OSF. CONCLUSIONS: Translation,
      conversion and definition ambiguities are a source of inter-observer variability
      and increase the risk of classification and/or selection biases. This gives rise
      to particular concern in the design and analysis of multicenter trials of meta
      analysis, and improvement of these scoring systems should be envisaged in the
      future.

PMID- 7650261
TI  - The laryngeal mask airway in critical care medicine.

PMID- 7650263
TI  - Thrombo-embolism during amniotic fluid embolism.

PMID- 7650259
TI  - Splanchnic metabolism associated with liver metastasis.
AB  - Metastatic liver disease can modify the metabolic response to critical illness.
      Systemic lactic acidosis may arise from an increased production due to inadequate
      peripheral tissue oxygen transport, altered metabolic function such as depressed
      pyruvate oxidation or insufficient hepatic clearing capacity due to tumor
      replacement of functional liver mass. Hepatic venous catheterization in a patient
      with extensive metastatic melanoma to the liver and adult respiratory distress
      syndrome indicated a marked disparity between whole body and liver oxygenation
      which may arise due to a markedly stepped up splanchnic oxygen utilization
      unmatched by a proportionate rise in regional oxygen delivery. Since some
      neoplasms may exhibit increased metabolic activity, it is suspected that these
      metastatic lesions may have contributed to the observed regional hypermetabolism
      thereby worsening hepatic hypoxia and exacerbating lactic acidosis. This case
      also illustrates the difficulties in interpreting global indicators of metabolic
      function and oxygenation in critically ill patients.

PMID- 7650264
TI  - Left atrial contusion with intramyocardial hematoma after a blunt chest trauma.

PMID- 7650262
TI  - The pathogenesis of ventilator-associated pneumonia: I. Mechanisms of bacterial
      transcolonization and airway inoculation.
AB  - Ventilator-associated pneumonia (VAP) is an infection of the lung parenchyma
      developing in patients on mechanical ventilation for more than 48 h. VAP is
      associated with a remarkably constant spectrum of pathogenic bacteria, most of
      which are aerobic Gram-negative bacilli (AGNB) and, to a lesser extent
      Staphyloccus aureus. Most authorities agree that VAP develops as a result of
      aspiration of secretions contaminated with pathogenic organisms, which appear to
      be endogenously acquired. These pathogens gain access to the distal airways by
      mechanical reflux and aspiration of contaminated gastric contents and also by
      repetitive inoculation of contaminated upper airway secretions into the distal
      tracheobronchial tree. Persistence of these organisms in the upper airways
      involves their successful colonization of available surfaces. Although exogenous
      acquisition can occur from the environment, the rapidity at which critically ill
      patients acquire AGNB in the upper airways in conjunction with the low rate of
      AGNB colonization of health-care workers exposed to the same environment favors
      the presence of endogenous proximate sources of AGNB and altered upper airway
      surfaces that are rendered receptive. Proximate sources of AGNB remain unclear,
      but potential sites harboring AGNB prior to illness include the upper
      gastrointestinal tract, subgingival dental plaque, and the periodontal spaces.
      Following illness or antibiotic therapy, competitive pressures within the
      oropharynx favor AGNB adherence to epithelial cells, which lead to oropharyngeal
      colonization. Similar dynamic changes in contiguous structures (oropharynx,
      trachea, sinuses, and the upper gastrointestinal tract) lead to the
      transcolonization of these structures with pathogenic bacteria. Following local
      colonization or infection, these structures serve as reservoirs of AGNB capable
      of inoculating the lower airways. As the oropharynx becomes colonized with AGNB,
      contaminated oropharyngeal secretions reach the trachea, endotracheal tube, and
      ventilator circuit. Contaminated secretions pooled above the endotracheal tube
      cuff gain access to the trachea and inner lumen of the endotracheal tube by
      traversing endotracheal tube cuff folds. Amorphic particulate deposits containing
      AGNB form along the endotracheal tube and are capable of being propelled into the
      distal airways by ventilator-generated airflow or by tubing manipulation.
      Bacteria embedded within this type of amorphous matrix are particularly difficult
      for the host to clear. If host defenses fail to clear the inoculum, then
      bacterial proliferation occurs, and the host inflammatory response progresses to
      bronchopneumonia.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7650265
TI  - Accidental delayed dilation of traumatic arteriovenous fistula following
      hemodialysis catheterization using a guide wire--left subclavian artery to
      jugular venous arch fistula.

PMID- 7650266
TI  - Prolonged paralysis in critically ill patients.

PMID- 7650268
TI  - The analyst under stress: issues of technique.

PMID- 7650269
TI  - Telling about the analyst's pregnancy.
AB  - Pregnancy is one of several events in the life of an analyst which may affect an
      analysis, calling for special technical considerations. For the analyst, this
      exception to the tenet of anonymity, along with countertransference guilt,
      narcissistic preoccupation, heightened infantile conflicts, and intense patient
      responses, may stimulate anxiety that becomes focused on the timing and manner of
      informing the patient. For the patient, preoccupation with the timing of the
      telling may serve as a displacement from other meanings of the pregnancy.
      Candidate analysts may face particular difficulties managing the impact of their
      pregnancies on control cases. We address practical and technical considerations
      in telling, the transference and counter-transference surrounding it, ethical
      concerns, and the challenges of supervising a pregnant candidate.

PMID- 7650267
TI  - Reliability of tonometric intramucosal PCO2 measurement with a phosphate-buffer
      solution.

PMID- 7650270
TI  - The Pope's confessor: a metaphor relating to illness in the analyst.
AB  - This paper examines some of the internal and external eventualities in the
      situation of illness in the analyst. The current emphasis on the use of the self
      as part of the analyzing instrument makes impairments in the analyst's physical
      well-being potentially disabling to the analytic work. A recommendation is made
      for analysts, both individually and as a professional group, to always consider
      this aspect of a personal medical problem.

PMID- 7650271
TI  - Psychoanalysis and psychotropic medication.

PMID- 7650272
TI  - The continued usefulness of psychoanalysis in the treatment armamentarium for
      panic disorder.
AB  - The case of a late adolescent with panic disorder and obsessive-compulsive
      disorder is described. The patient experienced resolution of both disorders in
      brief psychodynamic psychotherapy, but required psychoanalysis in order to make
      inroads into his restricted life-style. This case illustrates the continued
      usefulness of psychoanalysis in the treatment of such patients.

PMID- 7650275
TI  - Classics revisited: introduction. Panel report.

PMID- 7650274
TI  - The phallic castration complex and primary femininity: paired developmental lines
      toward female gender identity.
AB  - I suggest that two developmental lines contribute to the achievement of female
      gender identity. One is rooted in the phallic castration complex, and the other
      in primary femininity. Far from being mutually exclusive, the two comprise
      necessary aspects of every girl's progress toward becoming a woman. To that
      extent, every woman's analysis will include the analysis of compromise formations
      that emerge from both. In distinguishing clinical manifestations of each
      developmental line, I suggest that it may be useful to conceptualize primary
      femininity and the phallic castration complex as affect-defense configurations
      which incorporate two fundamentally different ideas about danger. In conflicts of
      primary femininity, danger is anticipated: anxiety is the signal for compromise
      formation, since what is actually possessed (the female genital) is valued and is
      therefore imagined as subject to danger. In the phallic castration complex,
      danger is imagined already to have occurred. Depressive affect becomes the
      primary motive for defense, based on a fantasy that what is valued (the male
      genital) has already been lost. This distinction may facilitate our efforts to
      specify exactly how recent revisions in theories of female development have
      explicit implications for practice.

PMID- 7650273
TI  - Medication use in training cases: a survey.
AB  - Though the introduction of psychotropic medication for the treatment of
      depression and anxiety was first greeted by the psychoanalytic community with
      overt opposition, in recent years the belief that medication and psychoanalysis
      are incompatible is being reconsidered. A study at the Columbia University Center
      for Psychoanalytic Training and Research showed that in 29% of candidate training
      cases medication was used in combination with psychoanalysis. In most cases the
      indication for medication was a diagnosis of depression, and an antidepressant
      was prescribed. The implication of these data with respect to the impact of
      medication on analytic process and candidate training is discussed.

PMID- 7650276
TI  - Classics revisited: Freud's Papers on Technique. Panel report.

PMID- 7650278
TI  - Classics revisited: Leo Stone's The Psychoanalytic Situation. Panel report.

PMID- 7650277
TI  - Classics revisited: Heinz Kohut's The analysis of the Self. Panel report.

PMID- 7650279
TI  - Agoraphobia and panic states. Panel report.

PMID- 7650280
TI  - On "recovered memories".

PMID- 7650281
TI  - On Brenner's "The dissociative character".

PMID- 7650282
TI  - MacIntosh study faulted.

PMID- 7650283
TI  - Sarnoff responds to Dowling's review.

PMID- 7650284
TI  - Gender identity disorder in a girl: insights from adoption.
AB  - Gender identity disorder in girls is reported far less frequently than in boys.
      The analysis of a six-year-old adopted girl with gender identity disorder is
      presented to show the importance of the mother-infant relationship and of
      parental, especially maternal, attitudes toward gender in the normal development
      of gender identity and gender role definition. This child's unusual history
      included a late adoption, with clear evidence of separation trauma, and the
      ongoing influence of maternal infertility. Her symptoms of gender identity
      disorder appeared before her second birthday and were well established by three
      years of age. The analysis, from age six to thirteen, achieved a better
      adaptation to her gender. Her masculine strivings gradually became incorporated
      into an essentially feminine orientation.

PMID- 7650285
TI  - Do actions speak louder than words? A query into an enigma in analytic theory and
      technique.
AB  - While action is increasingly viewed as ubiquitous throughout psychoanalytic
      treatment, our understanding of why it occurs is limited by rudimentary views of
      verbalization and action. Dynamic and genetic interpretations of action, usually
      given at a time of resistance impasse, give only a partial explanation of the
      phenomenon. The question is explored of why the behavior may appear in the form
      of action, as well as its implication for interpretive strategies. A major
      premise is that the role of the ego has been overlooked, especially modes of
      thinking associated with earlier developmental levels.

PMID- 7650286
TI  - The role of analyst's expectations in clinical technique: reflections on the
      concept of resistance.
AB  - The role played by an analyst's expectations in technique is taken up via
      consideration of the advantages and disadvantages of the concept of resistance. A
      conception of resistance is presented, and specific clinical interventions
      suggested by it are illustrated and discussed. The principle of even hovering
      attention as an ideal analytic attitude is criticized.

PMID- 7650287
TI  - Interpretation and expectation: the anxiety of influence.
AB  - Interpretations go beyond assigning unconscious meaning to analytic material.
      They inevitably communicate the analyst's assessments of the patient's present
      and past conflicts, and his expectations for their future resolution. The
      analyst's estimation of a patient's potential, as well as his personal investment
      in helping the patient realize that potential, is embedded in the interpretive
      process. Although careful analysis of unintended interpretive influences on a
      patient's transference and resistance is required to assure relative neutrality,
      there remains a residual conditioning effect of interpretations that catalyzes
      the analytic process and reinforces a patient's efforts to change.

PMID- 7650288
TI  - Treatment of AIDS with drugs targeted to inhibit different stages of the HIV life
      cycle.

PMID- 7650289
TI  - Leukocyte Interleukin, Inj. (LI) augmentation of natural killer cells and
      cytolytic T-lymphocytes.
AB  - A serum free lymphokine preparation derived from human buffy-coat mononuclear
      cells [buffy coat interleukins (BC-IL)], also named Leukocyte Interleukin, Inj.
      (LI), trade name Multikine, containing glycosylated interleukin-2 (IL-2) among
      other interleukins, was tested in three head and neck cancer patients. They
      responded with tumor regressions associated with increased tumor infiltration of
      lymphocytes and tumor cell lysis indicating an LI Interleukin-2 induced tumor
      specific immune response. To determine whether these responses elicited by LI
      were IL-2 driven, augmentation of natural killer cells (NKC) and cytolytic T
      cells (CTL), was tested both in vitro and in vivo. A single intraperitoneal
      (i.p.) injection of LI in adult BALB/c mice at doses of 3, 10, 30 and 100 of IL-2
      equivalence International Units per mouse, led to significant (p < 0.01)
      augmentation of NKC cytotoxicity to YAC tumor cells. NKC cytotoxicity remained
      elevated for 7 days, peaking at 5 days post-treatment. Multiple treatments with
      LI did not increase NKC cytotoxicity above single injection, nor did it lead to
      NKC hyporesponsiveness. The most effective treatment routes leading to heightened
      NKC cytotoxicity were: intravenous(i.v.) > intraperitoneal (i.p.) > intramuscular
      (i.m.) > subcutaneous (sc). Significant (p < 0.05 to < 0.01) NKC cytotoxicity was
      achieved by all four routes. In vitro incubation of murine splenocytes with 30
      and 100 International Units/ml (IU/ml) of IL-2 equivalent elevated NKC
      cytotoxicity significantly (p < 0.01) at all effector to target cell ratios
      tested and exceeded the response achieved with rhIFN gamma. NKC cytotoxicity of
      human peripheral blood lymphocytes (HPBL) against the K562 human tumor cell was
      also significantly elevated (p < 0.01) at the 30 and 100 IU/ml doses and (p <
      0.05) at 3 and 10 IU/ml doses. Of particular interest was the significant
      increase of CTL response in HPBL generated by LI. Significant activity (p < 0.01)
      was achieved with levels of 10, 30 and 100 IU/ml at effector to target cell
      ratios as low as 6 to 1. These results indicate that the LI containing IL-2 led
      to the significant increase in NKC and CTL cytolytic activities. Relatively lower
      doses of LI were needed to attain equivalent cytolytic activities as achieved
      with rhIL-2 or rhIFN gamma.

PMID- 7650290
TI  - Simultaneous intraperitoneal administration of OK-432 and serum enhances
      superoxide generation from migrated polymorphonuclear leukocytes, with special
      emphasis on the role of complements.
AB  - Superoxide and its derived active oxygen species are responsible for the
      polymorphonuclear leukocyte (PMN)-mediated tumoricidal activity which is
      typically shown in the intraperitoneal administration of OK-432, a biological
      response modifier, for cancer ascites. We examined the effects of intraperitoneal
      administration of OK-432 with or without syngeneic serum on superoxide generation
      from PMNs which migrated in the peritoneal cavity using the new method of
      Cypridina luciferin analog-dependent chemiluminescence for the detection of
      superoxide. PMNs harvested from rat peritoneal cavity 6 h after the
      intraperitoneal administration of OK-432 (0.25KE/kg, or 2.5KE/kg) generated
      larger amounts of superoxide than those harvested after intraperitoneal injection
      of oyster glycogen (75mg/kg) when stimulated by opsonized zymosan or phorbol
      myristate acetate. Simultaneous intraperitoneal administration of OK-432 and
      syngeneic serum induced a greater increase in PMN superoxide generation than OK
      432 alone, which was reversed by a complement activation inhibitor (MX-1).
      Simultaneous injection of OK-432 and heat-inactivated syngeneic serum did not
      exhibit a significant increase in PMN superoxide generation as compared with OK
      432 alone. These results provide pharmacological evidence to the satisfactory
      therapeutic effects of the intraperitoneal administration of OK-432 with or
      without serum for patients with cancer ascites, and indicate that complements, in
      particular C5a, are involved in this enhanced PMN-derived superoxide generation
      induced by the simultaneous injection of OK-432 and serum.

PMID- 7650291
TI  - Effects of streptolysin O, picibanil (OK 432) and interferon alpha 2A on
      cytochrome P-450-dependent monooxygenases and arylamine N-acetyltransferase in
      rat liver.
AB  - Streptolysin O, a thiol-activated exotoxin from group A beta-haemolytic
      streptococci, caused a dose-dependent depression of aniline hydroxylase,
      aminopyrine N-demethylase and ethylmorphine N-demethylase activities when added
      into the hepatic microsomal mixtures from male rats at concentrations 0.02-0.4
      HU/mL in vitro. The activities of 7-ethoxycoumarin O-deethylase, 7-ethylresorufin
      O-deethylase and 7-pentylresorufin O-depentylase were not altered with the used
      concentrations of the toxin. Specific antibody against haemolytic action of
      streptolysin O added to incubation mixtures in vitro was not able to protect
      streptolysin-sensitive monooxygenases from the inhibition. The addition of
      streptolysin O (0.01-0.8 HU/mL) into the cytosol-containing medium did not
      significantly influence the activity of procainamide N-acetyltransferase.
      Immunomodulators picibanil (OK 432) and human recombinant interferon alpha 2A
      which are known to suppress oxidative metabolism in vivo in humans and animals,
      were without effect either on the cytochrome P-450-dependent monooxygenases or on
      the N-acetyltransferase activity when administered in vitro at the doses real in
      their clinical application (0.001-0.1 KE/mL of picibanil and 10-500 U/mL of alpha
      interferon).

PMID- 7650292
TI  - The suppression of macrophage secretion by calcium blockers and adenosine.
AB  - In an effort to examine the effects of calcium blockers and adenosine on
      superoxide, hydrogen peroxide, and nitrite secretions by mouse peritoneal
      macrophages, we have utilized the phenol red method, the superoxide dismutase
      inhibitable reduction of ferricytochrome c method, and the Griess reagent method
      to test products after treating periodate-elicited mouse peritoneal macrophages
      with verapamil, nifedipine, and adenosine. The results show that after treating
      the macrophages with chemicals 10 minutes before adding PMA (100 ng/ml), all
      three chemicals inhibited superoxide (O2-) and hydrogen peroxide (H2O2)
      secretions dose-dependently, yet they failed to suppress macrophage reactive
      oxygen intermediates (ROI) after a 24 hour treatment. On the other hand, calcium
      blockers, verapamil and nifedipine, could reduce nitrite secretion (NO2-), while
      adenosine did not show the ability to inhibit NO2-. This indicates that calcium,
      as a secondary messenger, is important for the production of ROI and RNI. The
      reason behind the loss of the ability to suppress macrophage ROI production in a
      24 hour treatment remains unexplored.

PMID- 7650293
TI  - Prostaglandins affect the respiratory burst of human neutrophils.
AB  - The effects of prostaglandins on superoxide generation by neutrophils were
      investigated, since these arachidonic acid metabolites are both involved in the
      early phase of the inflammatory process and during later stages of neutrophil
      function. Preincubation of these cells for five minutes with concentrations of
      PGE2 ranging from 10(-7) to 10(-4) M was able to significantly reduce superoxide
      production in PMA-stimulated neutrophils. Other pro-inflammatory PGs tested, such
      as PGE1, PGF1 alpha, PGF2 alpha, inhibited the respiratory burst. The PGE2
      induced inhibition was compared to that exerted by staurosporine, a PKC
      inhibitor. The effects of the two drugs were not additive, since the combinations
      of PGE2 and staurosporine reduced O2- production to the same extent as
      staurosporine alone. Possible interferences between PKA- and PKC-mediated
      transduction signals are discussed.

PMID- 7650294
TI  - Effect of methionine enkephalin on natural killer cell and cytotoxic T lymphocyte
      activity in mice infected with influenza A virus.
AB  - Methionine enkephalin (Met-Enk) was evaluated for efficacy as an immune activator
      and potential therapeutic agent in influenza A/NWS/33 (H1N1) viral infections in
      female BALB/C mice. Influenza infection was induced intranasally with an
      approximate 90% lethal dose of virus and mice were treated intraperitoneally with
      doses of 10, 3 and 1 mg/kg/day, with treatments given 24 h pre-, 24 h post- and
      72 h post-virus exposure. Splenocytes were assayed for natural killer cell (NK)
      and cytotoxic T lymphocyte (CTL) activity at time periods 76, 96 and 120 h post
      virus exposure. The 10 mg/kg dosage level significantly increased both CTL and NK
      activity at all time periods assayed. Other treatment schedules included single
      doses of 20, 10 and 3 mg/kg/day Met-Enk at either 24 h post- or 72 h post-virus
      exposure, with highly significant increases in NK and CTL activity noted after
      the latter treatment. The results of this study demonstrate the immunomodulatory
      effects of Met-Enk on NK and CTL in influenza infected mice and suggest a
      potential for therapeutic applications.

PMID- 7650295
TI  - Evaluation of cellular immune responses and soluble mediators in patients with
      chronic hepatitis C virus (cHCV) infection.
AB  - In 54 patients with cHCV infection, peripheral immune responsiveness and soluble
      mediator release were evaluated. Results demonstrate that in these patients
      phagocytosis and killing capacities exerted by polymorphonuclear cells and
      monocytes were profoundly depressed. At the same time, absolute numbers of CD3+,
      CD8+ and CD16+ cells were reduced, while the CD4(+)-CD8+ dependent antibacterial
      activity was also impaired. With special reference to soluble mediators, elevated
      amounts of both soluble interleukin-2 receptor and soluble intercellular adhesion
      molecule-1 were detected in sera of patients. By contrast, serum levels of tumor
      necrosis factor-alpha were within normal ranges, whereas interferon-gamma serum
      concentrations were decreased. Of note, in 18.5% of cHCV patients circulating
      levels of bacterial lipopolysaccharides (LPS) were detected by means of Limulus
      assay. In the Limulus+subset of patients, absolute numbers of CD14+ cells were
      reduced in a significant manner, this implying a putative monocyte-LPS
      interaction. In conclusion, the overall results indicate a condition of
      peripheral immune depression in cHCV patients with an exaggerated shedding of
      various mediators endowed with noxious effects for the host.

PMID- 7650296
TI  - Immunotoxicity of polyunsaturated fatty acids in serum-free medium.
AB  - To test the effect of purified polyunsaturated fatty acids on immune cells in
      vitro, human peripheral blood mononuclear cells and murine spleen cells were
      incubated in Opti-MEM medium without serum or even albumin and with 2-mercapto
      ethanol, insulin, transferrin and selenium as supplements. The human cells were
      stimulated with phytohemagglutinin and the murine cells were stimulated with
      Concanavalin A or lipopolysaccharide. Both human and murine cells were stimulated
      with recombinant human interleukin-2 to generate lymphokine activated killer
      cells. Linoleic and linolenic acids inhibited all of the immune responses tested,
      whereas docosahexaenoic and eicosapentaenoic acids did not. Similar effects were
      observed with cultured B16 F10 murine melanoma cells. Mixtures of linoleic and
      docosahexaenoic or eicosapentaenoic acids also inhibited the mitogenic response
      to phytohemagglutinin. Inhibition of lipid mediator production by indomethacin,
      quercetin, rutin, or nordihydroguariaretic acid, and addition of vitamins C and E
      with anti-oxidant activity failed to reverse the effects of linoleic acid. Thus,
      linoleic and linolenic acids appear to directly inhibit immune and tumor cells,
      at least under these conditions.

PMID- 7650297
TI  - Trichothecene mycotoxins depress the mononuclear-phagocytic system of young
      turkeys.
AB  - Macrophage cells isolated from the abdominal cavity of 21-day-old turkeys after a
      single injection of Sephadex suspension were used to quantitate the effects of
      direct in vitro exposure to deoxynivalenol (DON), 3-acetyldeoxynivalenol (3ac
      DON), scirpentriol (STO), or 15-acetylscirpenol (15-MAS). Macrophage monolayers
      were established on glass surfaces and cells were exposed to graded levels of
      individual mycotoxins for 1 hour: DON, 20-640 micrograms/microliters of culture;
      3ac-DON, STO, 15-MAS, 20-1280 micrograms/microliters of culture. All four
      mycotoxins caused dose-related effects. A concentration of 50
      micrograms/microliter DON caused a significant decrease in macrophage adherence,
      phagocytosis of opsonized SRBC, and number of opsonized SRBC per macrophage; at
      200 micrograms/microliter, phagocytosis of unopsonized SRBC was decreased. There
      were also increasing percentages of damaged macrophages with increasing DON doses
      as indicated by morphological alterations. Linear decreases in macrophage
      viability on exposure to 3-acDON and STO were observed. Moreover, STO and 15-MAS
      decreased macrophage adherence to glass and 3-acDON, STO, and 15-MAS induced
      macrophage morphological alterations. This study suggests that trichothecene
      mycotoxins may be immunosuppressive by affecting viability, adherence and
      phagocytic potential of mononuclear phagocytic cells of young turkeys.

PMID- 7650298
TI  - Immunotoxicity of cocaethylene.
AB  - This report describes the response of normal human T cells to stimulation in
      vitro in the presence of nano-micromolar concentrations of cocaethylene.
      Thymidine incorporation by concanavalin A-stimulated peripheral blood mononuclear
      cells was generally blunted by cocaethylene, albeit to different degrees
      depending upon the donor tested. The formation of concanavalin A-induced blast
      cells was decreased by increasing concentrations of cocaethylene. The production
      of interleukin-2 was also blunted in a dose-dependent fashion by cocaethylene,
      and this outcome was more consistently observed in stimulated peripheral blood
      mononuclear cells, compared to unseparated whole blood preparations. An inverse
      dose dependence was obtained in relation to the response of blast cells to
      recombinant human interleukin-2 in the presence of cocaethylene. These lines of
      evidence, taken together with our preliminary studies aimed at testing the effect
      of cocaethylene on the expression of certain membrane markers of activation
      (i.e., interleukin-2 receptor, transferrin receptor, serine aminopeptidase IV)
      and the expression of the proliferating cell nuclear antigen (cyclin PCNA),
      suggest that cocaethylene modulates relatively early events following T cell
      stimulation probably related to the interleukin-2 system.

PMID- 7650299
TI  - XXVI National Congress of the Italian Society of Endocrinology and XXth Pisa
      Endocrine meeting. Pisa, Italy, June 28-July 1, 1995. Abstracts.

PMID- 7650300
TI  - Nursing care and management of the elderly hip fractured patient.
AB  - 1. This study examined the effects of a geriatric orthopaedic nursing education
      program of care for the elderly hip fractured patient on select patient outcomes
      using a post-test nonequivalent control group design. 2. Nursing staff of a 26
      bed orthopaedic unit attended a day long education workshop focusing on common
      clinical problems the elderly patient experiences in the acute care setting. 3.
      This program provided nursing staff with sound knowledge for the provision of
      effective care to the acutely ill elderly patient, which resulted in improved
      patient outcomes and use of health care resources.

PMID- 7650301
TI  - Client self medication on a psychogeriatric unit.
AB  - 1. Changing trends in health care reflect increasing involvement with clients and
      families in the development of treatment plans, such as self medication planning.
      2. Acting as an advocate for the client, the nurse, in consultation with the
      client and the multidisciplinary team, developed a consumer-centered program,
      which allowed the client to master a complicated medication regime prior to
      discharge. 3. Discharge planning, follow-up, and evaluation of medication
      compliance, ensured continuity of care, successful outcomes, and reduced use of
      in-hospital health care dollars.

PMID- 7650302
TI  - Use of standardized nursing diagnoses and interventions in long-term care.
AB  - 1. Standardized language for patient assessment, nursing diagnoses and
      interventions provide a common language for professionals in long-term care. 2. A
      comprehensive Nursing Interventions Classification (NIC) was first published in
      1992 by the Iowa Intervention Project and the North American Nursing Diagnosis
      Association offers a comprehensive list of nursing diagnoses. 3. Most frequently
      used nursing diagnoses were: Self Care Deficit: Bathing/Hygiene, Self Care
      Deficit: Dressing/Grooming, Impaired Physical Mobility, Altered Thought Process,
      and Potential for Injury.

PMID- 7650303
TI  - Coping strategies in the nursing home.

PMID- 7650304
TI  - Long-term care organizational challenges and strategies art vs. regulation.
AB  - 1. Long-term residents of nursing homes, especially those with chronic
      deteriorating illnesses, may be at risk of overly rigorous treatment or
      abandonment because they do not fit the typical rehabilitative or terminal care
      planning models. 2. A proactive approach to care planning once rehabilitation is
      no longer an option emphasizes ongoing dialogue with the resident and family to
      determine their values and wishes for care, not merely determining the treatments
      they want withheld. 3. Although staff are enthusiastic about proactive,
      individualized, interdisciplinary planning for the care of residents, in
      actuality it is extremely difficult given current organizational constraints.

PMID- 7650306
TI  - In praise of older age.

PMID- 7650305
TI  - Applied humanism: a model for managing inappropriate behavior among mentally
      retarded elders.
AB  - 1. Federal regulations mandate that elderly persons with mental retardation are
      provided with specialized programming which meets with the needs of the
      individual. 2. Behavior modification techniques employed to provide services to
      elderly persons with mental retardation may not meet individual patient needs,
      lacks constructs which apply to nursing philosophy/process and is difficult to
      implement with today's limited resources. 3. The philosophy of Applied Humanism
      may be more congruent with nursing practice, can be utilized with nursing process
      and can meet the individual needs of elderly patients with mental retardation.

PMID- 7650307
TI  - The nurse-patient relationship.

PMID- 7650308
TI  - Self-care behaviors of older women with urinary incontinence.
AB  - 1. Despite the availability of effective treatments for urinary incontinence,
      many women self-manage incontinence and never have it evaluated or treated. 2.
      The vast majority of women in this study used one or more self-care behaviors to
      manage their incontinence; the most frequently used behaviors were locating or
      staying near bathrooms when out, voiding more frequently, and wearing some type
      of protective garment. 3. Most women reported that incontinence was not at all or
      only a little difficult to manage and were satisfied with the self-care behaviors
      they used to manage this problem despite the fact that most of these behaviors
      had little or no potential to reduce or eliminate their incontinence.

PMID- 7650309
TI  - [Emile Hervet (1913-1994)].

PMID- 7650310
TI  - [Effect of gonadotrophins, testosterone and growth hormone on spermatogenesis in
      two hypophysectomy patients].
AB  - Human chorionic gonadotrophin (hCG), human menopausal gonadotrophins (hMG) and
      somatotrope hormone (STH) were used for three months to induce spermatogenesis in
      a patient with azoospermia following hypophysectomy for Cushing's syndrome.
      Azoospermia reappeared when testosterone was substituted for hCG, despite
      continued treatment with FSH and STH. In a second patient who had undergone
      hypophysectomy for a craniopharyngioma presenting residual oligospermia, STH
      alone was uneffective in improving the sperm count. In both patients, the level
      of IGF-1 in seminal fluid was unchanged by STH despite increased serum IGF-1. The
      use of STH to induce spermatogenesis is discussed in light of its capacity to
      increase testosterone synthesis is response to hCG.

PMID- 7650311
TI  - [Use of a gonadoliberin agonist with or without gonadoliberin pulses for
      ovulation induction in ovarian dystrophies].
AB  - OBJECTIVES: Determine whether ovulation in dystrophic ovaries treated with GnRH
      agonist followed by GnRH pulses is due to the GnRH pulse or is patient-dependent.
      SITE. Endocrinology department, CHU Purpan, Toulouse, France. METHODS: Fifteen
      infertile patients, age range 22 to 35 years, with ovarian dystrophy were given
      GnRH agonist (Decapeptyl, 3.75 mg IM on day 3 of the cycle). In 5 patients, an IV
      pulse of GnRH was then given (6 micrograms/90 min). STATISTICAL ANALYSIS: Mann
      Whitney U test, corrected chi 2 test. RESULTS: Ovulation was achieved in 8/15
      cases (3/5 with and 5/10 without pulsatile GnRH p = NS) and 3 pregnancies
      (without pulsatile GnRH). Before treatment LH was higher in patients who had an
      ovulation. CONCLUSION: Ovulation can be achieved after GnRH agonist treatment in
      patients with dystrophic ovaries, with or without pulsatile GnRH, particularly if
      the initial LH levels are high.

PMID- 7650312
TI  - [Endocervical adenocarcinoma in situ. A histological entity to know].
AB  - We report diagnosis and treatment problems encountered in 4 cases of
      adenocarcinoma in situ (AIS) of the uterine cervix. The patients' ages ranged
      from 24 to 45 years. In 2 cases, Pap smears revealed strips of cells showing
      crowded nuclei and pseudostratification of AIS. In 3 cases, the diagnosis of AIS
      was confirmed from a colposcopically directed biopsy and, in the last case, from
      a surgical cone biopsy. In 3 cases, AIS was found to be associated with cervical
      squamous intraepithelial neoplasia. In all cases, it was difficult to rule out an
      early invasive adenocarcinoma. Three patients underwent total abdominal
      hysterectomy. The topographic data of lesions, notably the presence of
      endocervical AIS in hysterectomy specimen realised 4 years after conization, and
      a review of literature lead us to propose hysterectomy as a basic treatment. If
      conization is chosen, it should be cylindrical with adequate diameter and height.

PMID- 7650313
TI  - [Hysteroscopic treatment of uterine fibromas].
AB  - OBJECTIVES: To study retrospectively the long-term outcome after hysteroscopic
      treatment for intrauterine fibromas. METHODS: From October 1987 to January 1993,
      endouterine glycolol resection was performed in 239 patients with intrauterine
      fibromas. The operation had to be repeated in 39 patients due to incomplete
      resection or recurrent symptomatology. Patients presented with menometrorrhage,
      post-menopausal metrorrhage or infertility. RESULTS: Intra-operative
      complications were rare, mainly uterine perforations (7 cases) or metabolic
      syndromes due to reabsorption of glycine (5 cases). Mean follow-up was 2.5 years.
      The couple was sterile in 16 cases and 4 pregnancies were obtained (25%).
      Postmenopausal metrorrhage was present in 27 patients and the symptomatology
      disappeared in 24 (89%). In all, 196 women consulted for bleeding, good results
      were achieved in 81.1%. CONCLUSION: Endouterine resection is a sure, effective
      and long-lasting treatment for intrauterine fibromas.

PMID- 7650314
TI  - [Laparoscopic treatment of adnexal abscesses. A series of 39 patients].
AB  - OBJECTIVE: Evaluate short- and long-term follow-up of patients treated by
      laparoscopy and antibiotherapy for tubo-ovarian abscess. METHODS: We report a
      retrospective study of 39 patients treated from January 1983 to December 1992.
      Clinical files were examined and a questionnaire was mailed to patients. RESULTS:
      None of the patients needed to be reoperated for failure of the first
      laparoscopic treatment. A laparoscopic control after 3 month was done in 35
      cases, which allowed complete adhesiolysis in every patients. We performed distal
      tubal surgery in 17 patients at that time and oriented 6 patients directly
      towards IVF. Subsequent fertility, in 19 patients followed without contraception,
      demonstrated a rate of spontaneous intra-uterine pregnancy of 63%. CONCLUSION:
      This study confirms that laparoscopy remains the technique of choice in initial
      management of adnexal abscesses.

PMID- 7650315
TI  - [Physiopathology of pre-eclampsia: the role of immunology].
AB  - Preeclampsia complicating 3% of all births is an important cause of maternal
      death and is associated with an increased risks of neonatal morbidity and
      mortality. Among the numerous theories proposed to explain this syndrome, the
      concept of placental ischaemia resulting in a generalized disturbance of
      endothelial physiology is receiving increasing support. Maternal immunological
      systems is often solicited during normal pregnancy. Most likely the immunological
      system is implicated in preeclampsia. Its responsibility is protean.
      Trophoblastic antigens may not be properly recognized by maternal immunologic
      system, resulting in a defect of trophoblastic invasion of the myometrial segment
      of the spiral arteries. Preeclampsia does not seem to be accompanied with
      trophoblast immunological rejection by the mother. Some cases of preeclampsia are
      associated with autoimmune phenomena. The autoantibodies could be directed
      against phospholipids or/and trophoblastic membrane components. Activated
      neutrophils release a variety of substances, capable of mediating vascular
      damage. An imbalance between the protective antioxidant activity and aggressive
      oxidant mechanisms could initiate the endothelial lesions. Preeclampsia could be
      one presentation of immunodystrophism with local excess of harmful cytokines. The
      immunologic system is probably not the initiator of preeclampsia, but its role is
      ambiguous: either the protective immunologic mechanisms usually operating during
      pregnancy can be surpassed, or immunologic responses are inadequate and directly
      aggressive. A better understanding of the underlying immunologic anomalies will
      improve the nosologic classification of preeclampsia syndrome.

PMID- 7650316
TI  - [Choledochal cysts. A rare prenatal diagnosis].
AB  - Forty to sixty percent of main bile duct cysts are diagnosed before the age of 10
      years, often at the time of a complication. Current progress in echography now
      makes it possible to diagnose such cysts antenatally. Wze report a case
      discovered at 33 gestation and focus on the difficulty of formal antenatal
      diagnosis and the unpredictable, sometimes rapid, course of the disease. The main
      prognosis factor is the development of complications, especially liver fibrosis.
      Antenatal suspicion of main bile duct cyst is important as they can then be
      managed early after echographic confirmation during the first days of life with
      the potential reduction in severe complications.

PMID- 7650317
TI  - [An unusual etiology of hydramnios: prenatal cerebral vascular accident. Five
      cases].
AB  - Neurological anomalies of the fetus are classically reported as causes of
      hydramnios, but cerebral vascular events occurring in utero in the fetus are
      rarely mentioned. We observed five newborns with neurological complications
      during the neonatal period in which anomalies of cerebral vascularization were
      identified antenatally. The mothers had hydramnios during pregnancy. Several
      pathophysiological hypotheses have been proposed to explain the mechanism of
      hydramnios. Magnetic resonance imaging of the brain in the fetus has made it
      possible to identify such exceptional events with extremely poor prognosis and
      major sequelae.

PMID- 7650318
TI  - [Prenatal diagnosis of spontaneous thrombosis of the umbilical artery during the
      third trimester of pregnancy. Two cases with surviving infants].
AB  - Thrombosis of the umbilical artery was diagnosed in utero in two cases at the
      echography examination performed during the third trimester of gestation. The
      infants were born live and in good health. This is the first report of such
      antenatal diagnosis. The lack of prospective studies hinder the evaluation of
      fetal morbidity and mortality. Nevertheless, umbilical artery thrombosis is a
      high risk obstetrical situation since the potential risk of another thrombus in
      the second umbilical artery would lead to fetal death in utero. Careful
      monitoring is required with extraction of the fetus as soon as term allows or
      whenever the elements compromise fetal development.

PMID- 7650319
TI  - [Prenatal diagnosis of vasa previa with velamentous cord insertion, using Doppler
      color echography].
AB  - We report a case of prenatal diagnosis of vasa previa, using colour Doppler
      imaging. This affection is rare, but can be responsible for very severe fetal
      complications during the delivery. Elements of the diagnosis were demonstrated in
      the clinical case and discussed. This is a new use of transvaginal colour Doppler
      in Obstetrics.

PMID- 7650320
TI  - [Leptospirosis and pregnancy. Eleven cases in French Guyana].
AB  - The incidence of leptospirosis, a widespread antropozoonosis, is underestimated
      due to variable clinical presentations. The abortive effect of this disease, well
      known in animals, is only reported rarely in humans although transplacental
      transmission has been demonstrated. We report 11 cases of leptospirosis in
      pregnant women in French Guiana. The diagnosis was made on identification of the
      germ in maternal urine samples and/or on specific serology tests. Fetal death
      occurred in more than 50% of the cases due to premature abortion or in utero
      death. The rate of maternal-fetal transmissions is not known, but leptospirosis
      could be a not uncommon cause of perinatal deaths in endemic zones.

PMID- 7650321
TI  - [HELLP syndrome. Two cases observed at the University Hospital Center of
      Brazzaville (Congo)].
AB  - The HELLP syndrome is almost always encountered in patients with gravid
      hypertension. It is defined as the association between intravascular haemolysis,
      raised liver transaminase levels and thrombopenia. We report 2 cases of HELLP
      syndrome observed in the Gynecology-Obstetrics B ward in the Brazzaville (Congo)
      University Hospital in 1992. Frequency in the ward was estimated at 2.9% (2 cases
      among 67 patients hospitalized for pre-eclampsia). The two cases occurred at 29
      weeks gestation in young, black, primipartants in a context of severe pre
      eclampsia. The clinical course was rapidly favorable for the mother after
      delivery. One in utero fetal death occurred. Due to the number of maternal deaths
      recorded in the literature, we suggest that, in Africa, pregnancies should be
      interrupted in case of HELLP syndrome whatever the gestational age since proper
      medical facilities are need to care for these severe cases.

PMID- 7650322
TI  - [Marfan's syndrome and pregnancy. A case report and review of the literature].
AB  - Marfan's syndrome is a collagen tissue disease, identified at the end of the
      nineteenth century. The gene for this autosomal dominant disease lies on
      chromosome 15 and leads to a biochemical disorder yet to be described. We report
      a case of Marfan's disease in a gravid patient and discuss the complications
      which may occur. The main risk involves the cardiovascular manifestations of the
      disease with possible dissection or rupture of the aorta. Preventive surgery,
      with extra-corporal circulation is required when the diameter of the aorta is
      greater than 6 cm. Spontaneous abortions and risk of premature birth have also
      been reported. Delivery itself is not a major risk but should be planned in a
      setting allowing immediate transfer to a cardiac surgery unit. Pregnancy should
      be discouraged in patients with Marfan's syndrome if the aortic diameter is
      greater than 4 cm. When pregnancy occurs, echocardiographic examinations of the
      mother should be performed monthly for the first 6 months, then bimonthly.
      Prenatal diagnosis is of little interest, except to detect foetuses at risk at
      delivery.

PMID- 7650323
TI  - [Obstetrical prognosis of the post-cesarean uterus. 641 cases].
AB  - OBJECTIVES: A retrospective study of decisions made in a gynaecology department
      between January 1990 and December 1993 were analyzed in order to assess
      management of the post-cesarean uterus. METHOD: Among 9092 women who delivered in
      the department during the study period, there were 641 patients with a post
      cesarean uterus, due to a single prior cesarean section in 451. Results were
      analyzed and compared with those reported in the literature. RESULTS: Among the
      451 patients with a single scar, 184 (41%) delivered by elective cesarean section
      and in 267 (59%) a decision was made during labour. In this group of 267 patients
      with a single cicatrix who underwent a labour tests, 227 (85%) had a vaginal
      delivery compared with 40 (15%) in which the decision for cesarean section was
      made during labour. CONCLUSION: The results observed were comparable with those
      found in the literature. Management of pregnancy with post-cesarean uterus is now
      quite similar to that of a normal uterus. Epidural anaesthesia and ocytotin
      therapy as well as epidural labour triggering have had an important effect.

PMID- 7650324
TI  - [A case of a dizygotic twin pregnancy where superfetation seems indisputable].
AB  - A case of superfoetation is presented. Difference of age (3 weeks) between twins
      was established by ultrasound at 10 weeks, and persisted through subsequent
      echographic surveillance up to delivery at 39 of amenorrhea with twin 39 and 36
      weeks old. Only three publications in recent international literature are related
      to superfoetation. An attempt is made to try to understand superfoetation and to
      clearly differentiate it from superovulation.

PMID- 7650325
TI  - [Predictive value of anthropometric parameters for birth weight].
AB  - A random series of 1,000 parturients in 2 maternity wards in Kinshasa in 1992
      were studied. Several parameters affecting birthweight were measured. The
      predictive value of the Quetelet index, determined by Spearman correlation, was
      greater than the predictive value of skin folds, brachial circumference, adipose
      and muscular surfaces or fat mass and was slightly better than lean mass.
      Anthropometric measurements have certain inconvenience and other factors affect
      birthweight. These results suggest that the Quetelet index is a sufficiently
      precise tool for evaluating nutritional state. In addition, its use would allow
      more time for patient counselling. The longer doctor-patient dialogue could have
      an effect on prevention in the area of psycho-social stress. This latter factor,
      combined with the cumulated stress score, was found to be one of the 3 main
      factors in multiple linear regression evaluation of birthweights reported here.

PMID- 7650326
TI  - [Transmission of HIV in heterosexual couples].

PMID- 7650327
TI  - [Breast cancer after treatment for Hodgkin's disease].

PMID- 7650328
TI  - [Sacral colpopexy by the abdominal route: possible!].

PMID- 7650329
TI  - [Reduction of the number of amniocentesis screenings for trisomy 21 in women
      younger than 38 using plasma hCG and ultrasonography. Results of a study].

PMID- 7650330
TI  - An ultrasound scoring system for the diagnosis of liver disease in cystic
      fibrosis.
AB  - Advances in the management of the pulmonary complications of cystic fibrosis may
      result in an increasing prevalence of patients with chronic liver disease which
      may, therefore, become more important in the long-term management of cystic
      fibrosis patients. However, no simple and reliable test is available for the
      diagnosis of liver disease in cystic fibrosis. In particular percutaneous liver
      biopsy is highly inaccurate and potentially dangerous. Imaging techniques,
      including real-time ultrasound scanning, have been used to evaluate the hepato
      biliary system in cystic fibrosis and may represent the best available techniques
      for documenting hepatic involvement. The purposes of this study were to construct
      an ultrasound scoring system using three cardinal features of hepatic ultrasound
      in cystic fibrosis: coarseness of the parenchyma, nodularity of the liver edge
      and increased periportal echogenicity, to enable the accurate, early diagnosis of
      liver involvement in cystic fibrosis. The scoring system was validated by
      correlating the results against ultrasound markers of portal hypertension,
      clinical and haematological data. The scoring system proved to be reproducible
      and to correlate well with the markers of hepatic disease detailed above. The
      results also suggest that the scoring system may allow the identification of
      patients with pre-cirrhotic chronic liver disease and so may prove of value in
      selecting a sub-group of patients more likely to respond to therapy.

PMID- 7650331
TI  - No treatment, resection and ethanol injection in hepatocellular carcinoma: a
      retrospective analysis of survival in 391 patients with cirrhosis. Italian
      Cooperative HCC Study Group.
AB  - BACKGROUND/AIMS: This retrospective study was undertaken to obtain information
      relevant to the therapeutic strategy in single hepatocellular carcinoma
      associated with Child's A and B cirrhosis. METHODS: From a total of 1108
      consecutive patients with hepatocellular carcinoma, 391 patients with single,
      small (< or = 5 cm) hepatocellular carcinoma (260 in Child A class and 131 in
      Child B class) were observed: 120 were treated by surgical resection, 155 by
      percutaneous ethanol injection and 116 were untreated. The end point of the study
      was 3-year survival. The log rank test was used to compare survival among the
      different groups. RESULTS: In the Child A group the cumulative 3-year survival
      was 79% for surgery, 71% for percutaneous ethanol injection and 26% for no
      treatment (p < 0.001 for surgery versus no treatment, p < 0.001 for percutaneous
      ethanol injection vs no treatment). In patients comparable to the surgical group,
      i.e. potentially operable, survival was 80% for percutaneous ethanol injection
      and 30% for no treatment. In the Child B group the 3-year survival was 40% for
      surgery, 41% for percutaneous ethanol injection and 13% for no treatment (p <
      0.01 for surgery vs no treatment and p < 0.001 for percutaneous ethanol injection
      vs no treatment). CONCLUSIONS: Surgery and percutaneous ethanol injection improve
      survival in single hepatocellular carcinoma associated with Child A and B
      cirrhosis compared to untreated patients in the same Child class. A controlled
      study to identify factors affecting the choice of treatment is justified.

PMID- 7650332
TI  - Detection and analysis of replicating hepatitis C virus RNA in hepatocellular
      carcinoma tissues.
AB  - Although persistent hepatitis C virus infection is closely associated with the
      development of hepatocellular carcinoma, the nature of hepatitis C virus
      replication in the hepatocellular carcinoma tissue has not been fully
      characterized. To study this, carcinoma and non-carcinoma tissues were obtained
      from five patients with hepatocellular carcinoma. Total RNA was recovered from
      each tissue, and a portion of the envelope gene of replicating hepatitis C virus
      was amplified by minus-strand-specific reverse transcription and nested
      polymerase chain reaction. The amplified cDNA was examined by single strand
      conformation polymorphism analysis and sequencing. Hepatitis C virus replication
      was detected in both carcinoma and non-carcinoma tissues in four patients who
      were positive for serum hepatitis C virus markers. In one patient, a single
      species with identical envelope 2 genome was obtained from both carcinoma and non
      carcinoma tissues. In the other three patients, the replicating hepatitis C virus
      existed as a mixture of 2-5 species with different but highly homologous (82-99%)
      envelope 2 genomes (quasispecies populations). The constitution of viral
      populations was different between carcinoma and non-carcinoma tissues. A total of
      ten sequences were recovered; four sequences were found in both tissues, two were
      found in carcinoma tissues, and four were found in non-carcinoma tissues. The
      difference in the constitution of quasispecies populations between carcinoma and
      non-carcinoma tissues confirms the unequivocal replication of hepatitis C virus
      in both tissues, and may imply the presence of different biological properties
      among hepatitis C virus with different sequences.

PMID- 7650334
TI  - Factors predictive of response to interferon therapy in children with chronic
      hepatitis B.
AB  - BACKGROUND/AIMS: The efficacy of interferon therapy in Caucasian children with
      chronic hepatitis B is similar to that in adults. However, little information is
      available about factors predicting response to this therapy in children. We have
      performed a univariate analysis to assess the strength of association between
      basal variables and response, and a multivariate analysis to determine the
      combination of basal variables which give the best prediction of response in
      terms of sensitivity and specificity. METHODS: The basal parameters were studied
      in 50 children included in three different trials of interferon alpha therapy
      (360-700 MU/square meter of body surface, 2 or 3 times weekly for 12 to 24
      weeks). RESULTS: Of these, 18 (36%) were responders. In the univariate analysis,
      a higher histological activity (p < 0.05), a lower percentage of HBcAg-stained
      hepatocytes (p < 0.001), aspartate amino transferase and alanine aminotransferase
      levels (p < 0.05) and alanine aminotransferase peak prior to serum HBV-DNA
      clearance (p < 0.05), were associated to the response. In the multivariate
      analysis, the combinations of the percentage of HBcAg stained cells with alanine
      aminotransferase levels and with the histological activity index were the best
      variables for predicting response (sensitivity: 100% and specificity: 89% and
      86%, respectively). CONCLUSIONS: Factors predictive of response in children with
      chronic hepatitis B are similar to those found in adults, and may help in
      identifying those children with a better chance of responding.

PMID- 7650333
TI  - Expression of gap junction protein connexin 32 and E-cadherin in human
      hepatocellular carcinoma.
AB  - The expression of connexin 32, a major gap junction protein, and E-cadherin, an
      intercellular adhesion molecule that is supposed to be involved in the regulation
      of gap junctional intercellular communications, was examined
      immunohistochemically in seven specimens of human hepatocellular carcinoma and
      surrounding non-carcinomatous tissues. We found that the number of connexin 32
      positive spots per mm2 was significantly less in hepatocellular carcinoma tissues
      than in the surrounding non-carcinomatous cirrhotic tissues (4360 +/- 3390/mm2 vs
      10,030 +/- 3690/mm2; p < 0.01). The number in the latter was also significantly
      less than that in normal controls (23,560 +/- 4170/mm2). E-cadherin was expressed
      in all non-carcinomatous hepatocytes as well as carcinomatous cells, except for
      one case of Edmondson's grade III hepatocellular carcinoma. These results suggest
      an impairment of cell-to-cell communications in human hepatocellular carcinomas.

PMID- 7650335
TI  - Primary biliary cirrhosis is associated with specific changes in liver IgG
      bearing cell subpopulations.
AB  - BACKGROUND/AIMS: The density of total IgG-bearing cells and the distribution of
      their subclasses were studied in the liver of patients with primary biliary
      cirrhosis. METHODS: Immunohistochemistry and computerized image analysis were
      used to compare liver specimens from 18 patients with primary biliary cirrhosis
      and 28 with chronic hepatitis of different etiology. RESULTS: The density of
      total IgG-bearing cells was similar in the two groups. However, in patients with
      primary biliary cirrhosis the proportion of IgG3-positive cells was significantly
      higher than in patients with chronic hepatitis (53 +/- 7% vs. 7.5 +/- 2.4%) (p <
      10(-8)). Conversely, IgG1-positive cells were significantly less prevalent in
      patients with primary biliary cirrhosis than in chronic hepatitis patients (27 +/
      6.9% vs. 68 +/- 7.2%, p < 10(-8)). Stratification of patients with primary
      biliary cirrhosis according to histology did not show any difference in the
      distribution of IgG subclasses associated with the progression of disease.
      CONCLUSION: These data suggest a pathogenetic role of local IgG3-bearing cells in
      primary biliary cirrhosis.

PMID- 7650336
TI  - Sulphoxidation and sulphation capacity in patients with primary biliary
      cirrhosis.
AB  - We have previously reported an association of impaired S-oxidation with primary
      biliary cirrhosis. In order to confirm and further define this relationship, we
      retested S-oxidation capacity via three metabolic pathways and sulphation
      capacity via a fourth pathway. Metabolism of S-carboxymethyl-L-cysteine is
      polymorphic -20% of healthy individuals being poor S-oxidisers. We found 26% with
      primary biliary cirrhosis were poor S-oxidisers, compared with 36% with other
      liver disease and 25% of healthy controls. Differences were not statistically
      significant. S-oxidation of ranitidine is dependent upon flavin mono-oxygenases.
      We showed a non-significant trend toward less S-oxide in primary biliary
      cirrhosis and other liver disease, compared with healthy controls, with no
      significant difference between disease groups. Conversion of cysteine to sulphate
      depends predominantly on cysteine dioxygenase. Impaired activity may be reflected
      by decreased plasma sulphate and elevated cysteine. We found that the plasma
      cysteine: sulphate ratio was significantly elevated not only in primary biliary
      cirrhosis (p < 0.0001), but also in other liver disease (p < 0.0001), compared
      with healthy individuals. Sulphation capacity was studied by analysing
      paracetamol metabolism. Paracetamol sulphate and sulphate: glucuronide ratio were
      reduced in primary biliary cirrhosis compared with normal individuals, (p <
      0.05). A trend towards less sulphate in primary biliary cirrhosis compared other
      liver disease was not significant (p = 0.42). We conclude that although
      sulphation and some sulphoxidation pathways are impaired in primary biliary
      cirrhosis, we can currently find no evidence to substantiate the hypothesis that
      primary biliary cirrhosis is a disease specifically associated with poor S
      oxidation, as assessed via these metabolic pathways.

PMID- 7650338
TI  - Dental and periodontal disease in patients with cirrhosis--role of etiology of
      liver disease.
AB  - BACKGROUND/AIMS: Bacterial infections are frequent complications in patients with
      cirrhosis, especially in alcoholics. A potential source of infection may be
      dental foci. The aim of the study was to assess the role of cirrhosis and chronic
      alcoholism in the development of dental or periodontal disease. METHODS: Dental
      and periodontal examinations were performed prospectively in 97 patients with
      cirrhosis (alcoholic: 64, nonalcoholic: 33), in 68 alcoholics without cirrhosis
      and in 71 healthy subjects (subdivided into age groups: 21-30, 31-40, 41-50, and
      51-60 years). RESULTS: Measures of oral hygiene (p < 0.01), dental care (p <
      0.001), and periodontal parameters were worse and the number of teeth requiring
      treatment (p < 0.001) was higher in alcoholics with or without cirrhosis than in
      healthy subjects and nonalcoholic patients with cirrhosis. Alcoholics had a lower
      total number of teeth than patients without alcohol abuse and healthy controls (p
      < 0.05). The dental and periodontal status of patients with nonalcoholic
      cirrhosis did not differ from the control group. The severity and duration of
      liver disease had no influence on dental and peridontal disease. CONCLUSION: The
      presence of cirrhosis itself, therefore, is not a predisposing factor for dental
      and periodontal diseases. In alcoholics, these diseases appear to be caused
      primarily by bad oral hygiene and poor dental care.

PMID- 7650337
TI  - Alterations of Na+,K(+)-ATPase activity after hypoxia and reoxygenation in the
      perfused rat liver: an electron microscopic cytochemical study.
AB  - BACKGROUND/AIMS: Using the cerium technique for ultrastructural cytochemical
      studies, Na+,K(+)-ATPase activity was investigated in hypoxic and reoxygenated
      rat liver. METHODS: In the control group, the livers were perfused with
      oxygenated hemoglobin-free Krebs-Henseleit buffer for 1 h. For hypoxia (60 min),
      the flow rate of the perfusate was decreased and oxygen was replaced by nitrogen.
      For reoxygenation, the liver was reperfused under oxygenated conditions for 5 min
      after 60 min of hypoxia. RESULTS: In control livers, a strong Na+,K(+)-ATPase
      activity was detected at the basolateral membrane of hepatocytes while the apical
      membrane forming the bile canaliculi did not display any staining. In hypoxic
      livers, Na+,K(+)-ATPase activity had ceased in the plasma membrane of
      hepatocytes. In reoxygenated livers, Na+,K(+)-ATPase was rapidly reactivated in
      the basolateral hepatic membrane. The membrane of blebs generated during the
      hypoxic phase also showed enzyme activity. In addition, a striking accumulation
      of reaction product could be observed in about 10% of the apical membranes lining
      the bile canaliculi. CONCLUSION: The results indicate a plasticity of the
      Na+,K(+)-ATPase in hypoxic and reoxygenated rat liver.

PMID- 7650339
TI  - Liver transplantation and haemophilia A.
AB  - Liver transplantation has become the standard treatment for a variety of
      inherited metabolic disorders. We report on two patients who underwent successful
      transplantation for posthepatitis viral cirrhosis, which developed following
      blood factor replacement for haemophilia A. The second patient was transplanted
      before the occurrence of major complications of either his liver or haemophilic
      disease. We propose early liver transplantation to achieve metabolic cure of
      haemophilia.

PMID- 7650340
TI  - Liver transplantation for hepatic arteriovenous malformation in hereditary
      haemorrhagic telangiectasia.
AB  - Symptomatic hepatic involvement is a rare complication of hereditary hemorrhagic
      telangiectasia and most commonly consists of fibrosis or cirrhosis. We describe a
      33-year-old woman in whom multiple hepatic arteriovenous malformations led to
      high output cardiac failure and liver failure due to biliary necrosis with
      refractory biliary sepsis, requiring orthotopic liver transplantation. Hepatic
      arteriovenous malformations were the first manifestation of the disease and a
      similar asymptomatic hepatic tumour was subsequently detected in her 60-year-old
      father who also had the classical cutaneous stigmata of the syndrome.
      Unrecognised genetic factors may determine the clinical spectrum of hereditary
      haemorrhagic telangiectasia including the hepatic manifestations.

PMID- 7650341
TI  - Liver transplantation for severe acute liver failure after herbal medicine
      (Teucrium polium) administration.

PMID- 7650343
TI  - High rate of co-infection with different hepatitis C virus subtypes in HIV
      infected intravenous drug addicts in Spain. Hepatitis HIV Spanish Study Group.

PMID- 7650342
TI  - Hemobilia: a possible cause of jaundice in patients receiving anticoagulants.

PMID- 7650344
TI  - Absence of hepatitis C viral infection among patients with primary Sjogren's
      syndrome.

PMID- 7650345
TI  - Which lidocaine dose should be used for the MEGX liver function test?

PMID- 7650346
TI  - Patterns to follow ...

PMID- 7650347
TI  - Review of National League for Nursing and Center for Human Caring videotape "a
      guide to applying the art and science of human caring: a consultation with Jean
      Watson and colleagues," Parts 1 and 2.

PMID- 7650348
TI  - Toward an understanding of energetic healing, Part 1: Energetic structures.
AB  - The purpose of this article is to describe one understanding of structures
      involved in energetic healing, which is defined as healing occurring at the
      quantum and electromagnetic levels of a person, plant, or animal. Characteristics
      of electromagnets, direct electric currents, Fourier analyzers, and L-C circuits
      are discussed and applied to the human being. Human electromagnetic
      characteristics are compared to descriptions of auras, meridians, and chakras.
      Quantum and chaos theories are presented and applied to the question of the
      mechanism of energetic healing.

PMID- 7650349
TI  - Toward an understanding of energetic healing, Part 2: Energetic processes.
AB  - The purposes of the article are to discuss the role of consciousness and quantum
      processes in energetic healing and to present the author's theory of energetic
      healing. Two opposing views of consciousness are reviewed: consciousness as
      emerging from material processes and consciousness as primary. Three quantum
      physics' theories are discussed: potentiality/actuality, observer-created
      reality, and consciousness-created reality. Psychosynthesis is offered as a model
      for the dimensions of a psyche that could be involved in consciousness-created
      reality and in energetic healing. A theory of energetic healing is outlined and
      applied to holistic nursing.

PMID- 7650350
TI  - Humor: a holistic nursing intervention.
AB  - The stressors of illness, together with the stressors of modern life, challenge
      the coping skills of all clients. Humor can be an important tool in a holistic
      approach to coping with illness. Despite this, the use of humor as a nursing
      intervention is not yet common. This article explores the physiological,
      psychological, social, and spiritual effects of humor and suggests situations for
      which humor may be helpful. The skills needed by the nurse to use humor are
      described. Methods for client assessment and ways to implement and evaluate humor
      are also discussed.

PMID- 7650352
TI  - Effect of relaxation with guided imagery on anxiety, depression, and self-esteem
      in primiparas.
AB  - A pretest-posttest experimental design with a convenience sample of 60 subjects
      was used to examine the effects of a relaxation with guided imagery protocol on
      anxiety, depression, and self-esteem in primiparas during the first 4 weeks of
      the postpartum period. The results showed that the experimental group had less
      anxiety and depression and greater self-esteem than did the control group at the
      end of the period. Positive correlations were obtained between anxiety and
      depression; negative correlations between self-esteem and anxiety and depression.
      All findings were significant at the .05 level.

PMID- 7650351
TI  - Music for sleep disturbance in the elderly.
AB  - Twenty-five elderly, community-based subjects with self-perceived sleep
      disturbances participated in this descriptive pilot study. Subjects listened to
      classical and New Age music before bedtime when a sleep disturbance was
      identified. Daily logs were kept by each participant to evaluate the
      effectiveness of the intervention. Twenty-four (96%) of the subjects reported
      improved sleep using this self-administered intervention.

PMID- 7650353
TI  - Nursing interventions for spiritual care: preferences of the community-based
      elderly.
AB  - This descriptive correlational study examined the relationships between the three
      concepts of core spiritual experience, spiritual perspective, and self
      transcendence, as well as the spiritual-care nursing interventions preferred by a
      convenience sample of 50 community-based older adults. Results of single-session
      interviews indicated significant positive correlations among the three concepts.
      Spiritual interventions preferred by older adults were those interventions
      focusing on the therapeutic communication skills of the nurse and the nurse's
      attitude and approach toward clients. Overall, older adults who believed in a
      Higher Power and whose beliefs were prominent in their lifestyle rated spiritual
      nursing interventions as more important than did older adults who did not hold
      strong beliefs in a Higher Power and whose spiritual beliefs were not prominent
      in their lifestyle. Findings give direction for providing spiritual nursing care
      to older adults.

PMID- 7650354
TI  - Are patients really 'revenue centers'?

PMID- 7650356
TI  - Alternative care: what is it? Does it work?

PMID- 7650355
TI  - Physician urges stand against 'industrialization of medicine'.

PMID- 7650357
TI  - Unconventional medicine.

PMID- 7650358
TI  - Managed care creates conflicts of interest. Interview by Bob Carlson.

PMID- 7650359
TI  - Unconventional medicine in Indiana.

PMID- 7650361
TI  - AMA looks at ways to reform Medicare.

PMID- 7650360
TI  - State health reform bill pleases physicians.

PMID- 7650362
TI  - AMA's study of federation looks at future needs, concerns.

PMID- 7650363
TI  - Hodgkin's lymphoma presenting in two siblings with atypical pseudocholinesterase.
AB  - A 21-year-old white man was admitted with a diagnosis of mixed cellularity
      Hodgkin's lymphoma for staging laparotomy. His family history was positive for a
      brother who had both Hodgkin's lymphoma and atypical pseudocholinesterase. Serum
      pseudocholinesterase activity, dibucaine number and fluoride number were
      obtained, revealing markedly decreased pseudocholinesterase activity and
      dibucaine number, with an only slightly decreased fluoride number, consistent
      with homozygous type E1a atypical pseudocholinesterase. After induction of
      anesthesia using vecuronium, a staging laparotomy was performed without
      complication. Through a discussion of what is known of the genetics of Hodgkin's
      disease and atypical pseudocholinesterase, we conclude that the association
      between the two conditions is very rare but more likely due to chance than to
      genetic linkage.

PMID- 7650364
TI  - From the museum.

PMID- 7650365
TI  - Defective ceramide response in C3H/HeJ (Lpsd) macrophages.
AB  - Lipid second messengers are gaining recognition as important mediators of
      extracellular signals. One such lipid, ceramide, generated from membrane
      sphingomyelin following stimulation with TNF-alpha, IL-1 beta, or IFN-gamma,
      activates ceramide-activated kinase (CAK). A recent study demonstrated that LPS
      activated CAK without generating ceramide, suggesting that the LPS stimulation of
      cells mimics the second messenger function of ceramide. To compare ceramide to
      LPS signaling, we assessed the ability of LPS-responsive (Lpsn) and LPS
      hyporesponsive (Lpsd) macrophages to respond directly to ceramide for enhanced
      expression of LPS-inducible genes. In contrast to macrophages from C3H/Ouj (Lpsn)
      mice, C3H/Hej (Lpsd) macrophages failed to respond to cellpermeable analogues of
      ceramide (C2,C6,C16) or sphingomyelinase. These results suggest that a common
      critical molecule, encoded by the Lps gene, regulates both ceramide and LPS
      signaling pathways.

PMID- 7650366
TI  - Molecular cloning of NKB1. A natural killer cell receptor for HLA-B allotypes.
AB  - The expression of certain MHC class I allotypes by potential target cells can
      inhibit NK cell-mediated cytotoxicity. We recently identified the NKB1 surface
      Ag, expressed on T and NK cell subsets, as a putative inhibitory receptor for HLA
      B class I molecules possessing the Bw4 serologic epitope. NKB1 is a 70-kDa
      glycoprotein that after deglycosylation migrates as a 50-kDa protein as
      determined by SDS-PAGE. A cDNA encoding the NKB1 receptor was cloned from a
      NKB1+T cell cDNA library by expression in COS-7 cells using the anti-NKB1 mAb
      DX9. NKB1 is a member of the lg superfamily containing three lg-like domains in
      the extracellular region and is related to the recently identified family
      (p58/NKAT) of human NK and T cell surface molecules that appear to function as
      inhibitory receptors for HLA class I.

PMID- 7650367
TI  - Expression of Bcl-2, Bcl-x, and Bax after T cell activation and IL-2 withdrawal.
AB  - Bcl-2, bcl-x, and bax genes code for proteins that affect the susceptibility of
      cells to apoptosis. In general, the expression of bcl-2 or bcl-x inhibits
      apoptosis while bax promotes apoptosis. We examined the levels of these proteins
      by immunoblotting in resting and activated T cells and in thymocytes. Bcl-2 and
      Bax proteins vary coordinately, but Bcl-x varies independently: Bcl-2 and Bax are
      higher in splenic T cells than in thymocytes, and their levels increase even more
      after T cell activation. In contrast, Bcl-x is almost undetectable in splenic T
      cells but is manyfold greater in thymocytes and in activated splenic T cells.
      When CTLL-2 cells or activated T cells are starved of IL (IL-2), the level of Bcl
      x but not Bcl-2 protein drops before the onset of apoptosis. Stable transfection
      of either bcl-2 or bcl-x expression plasmids promotes the survival of CTLL-2
      cells in the setting of IL-2 withdrawal. Over 70 to 90% of the transfected cells
      remain viable at 48 h after IL-2 withdrawal when all of the control transfected
      cells are apoptotic. These findings suggest that a decrease in Bcl-x protein
      levels precedes apoptosis after IL-2 withdrawal in T cells and that transfected
      bcl-2 promotes survival after IL-2 withdrawal by functionally masking this drop
      in Bcl-x.

PMID- 7650368
TI  - Marked conservation of complementarity-determining region 3 of the beta-chain of
      TCRs recognizing a mycobacterial heat shock protein 60-derived peptide with
      strong sequence similarity to human heat shock protein 60.
AB  - The variable gene usage and sequence of human TCRs specific for a particular
      MHC/peptide combination have been investigated. The peptide comprises amino acids
      456-466 of the 65-kDa Mycobacterium tuberculosis heat shock protein (hsp60), and
      is recognized in the context of HLA-DP. TCRs from both synovial fluid and
      peripheral blood (PB)-derived T cell clones used only five different V beta
      genes, three of which are closely related (V beta 6.7a, V beta 6.7b, and V beta
      21.3). Among TCRs using these three genes there was marked conservation of the
      beta-chain sequence, whereby complementarity-determining region 3 (CDR3)
      contained an amino acid motif (*R*G*, amino acids 96-100) in association with
      either J beta 1.4 or J beta 2.5. These conclusions were strengthened by analysis
      of peptide-stimulated T cell lines that revealed not only TCR beta-chain
      sequences identical with those seen in T cell clones, but also additional beta
      chains with similar CDR3 region sequences and J gene usage. In contrast, T cell
      lines derived by using IL-2 or a control peptide revealed variable usage of V
      beta and J beta genes; V beta 6.7a/b sequences from these lines and from freshly
      isolated PB did not contain the CDR3 motif noted in TCRs from Ag-specific T
      cells. We suggest that the remarkably limited diversity of TCRs noted in this
      study is a consequence of the similarity between the mycobacterial hsp60 peptide
      and the equivalent peptide from human hsp60, and reflects the trimming of the TCR
      repertoire required to maintain self-tolerance.

PMID- 7650369
TI  - Autoimmunity caused by ignorant CD8+ T cells is transient and depends on avidity.
AB  - RIP-Kb mice, which express H-2Kb (Kb) molecules on their pancreatic beta cells,
      were used to examine the requirements for induction of autoimmune diabetes caused
      by CD8+ T cells. Previous studies showed that when these mice were crossed to
      mice expressing a Kb-specific TCR transgene, those CD8+ cells expressing the
      highest density of the transgenic TCR (presumably the highest avidity cells) were
      deleted intrathymically due to aberrant expression of Kb at this site. The
      remaining low avidity cells ignored Kb-bearing beta cells, even after priming,
      but were able to cause autoimmune diabetes when supplied with Il-2. To examine
      the properties of high avidity autoreactive CD8+ T cells, the thymic compartment
      of RIP-Kb mice was replaced with normal tissue to enable the maturation of CD8+
      cells expressing the highest density of the transgenic TCR. These high avidity
      cells generally ignored Kb-expressing beta cells, but became autoaggressive after
      priming. Importantly, analysis of islet infiltration by CD8+ T cells revealed the
      presence of infiltrating cells in all mice examined within 3 wk of priming, but
      such infiltration was not usually apparent at later time points. In some cases,
      multiple primings were necessary for full development of autoimmunity. This
      implied that beta cells could act as transient targets for CD8+ T cell attack but
      could not sustain the stimulation of primed CD8+ cells. These studies indicate
      that the duration of priming stimulus and the avidity of the autoreactive CD8+
      cells profoundly influence the severity of autoimmune disease.

PMID- 7650370
TI  - Biased liver T cell receptor V beta repertoire in a murine graft-versus-host
      disease model.
AB  - Murine graft-vs-host disease (GVHD) results in destruction of small bile ducts in
      the liver. We analyzed the TCR V beta repertoire of lymphocytes isolated from the
      livers and spleens of individual B10.D2 into irradiated BALB/c GVHD mice by means
      of two-color immunofluorescence. Each mouse showed an increase in at least one V
      beta population in the liver and spleen, but the expanded V beta populations were
      heterogeneous and variable among individual GVHD mice. Overall, the repertoire of
      liver CD4 cells was biased toward V beta 2 and 3 expression with 65 and 88% of
      mice, respectively, showing an increase in these subsets. The splenic CD4 cell
      repertoire was biased toward V beta 3 and 4 expression (50% of mice each). The
      repertoire of CD8 cells was less biased with 20 to 35% of mice showing expansions
      of V beta 3+, 4+, 5+, 6+, 8.1+, 8.2+, and 8.3+ T cells in both the liver and
      spleen. V beta 2+ CD4 cells were increased preferentially in the liver compared
      with the spleen. These results indicate that the infiltrating liver and splenic T
      cells are polyclonal and suggest that donor T cells recognize multiple host non
      MHC Ags in this GVHD model. Alloantigens recognized by V beta 2+ CD4 cells appear
      to be selective for the liver. Expansion of V beta 3+ CD4 cells may reflect
      recognition of the host Mls-3 superantigen.

PMID- 7650371
TI  - Regulation of human B cell function by recombinant CD40 ligand and other TNF
      related ligands.
AB  - To assess the potential of CD40 ligand (CD40L) and the related molecules CD27
      ligand (CD27), CD30 ligand (CD30L), and membrane TNF-alpha to stimulate B cell
      responses, expression of these proteins in the baculovirus system was performed.
      Sf9 cells expressing these membrane molecules were cultured with normal human B
      cells and a variety of B cell lines to assess the functional outcome. The signal
      provided by CD40L promotes aggregation of B cells, stimulates vigorous
      proliferation, and induces germ-line transcription of downstream heavy chain
      constant region genes in the absence of cytokine costimulation. In contrast,
      CD27L, CD30L, and TNF-alpha had no effects on B cell proliferation. CD27L and TNF
      alpha had no effect on the induction of germ-line transcripts, whereas CD30L
      consistently inhibited constitutive and CD40L-induced germ-line transcription of
      the epsilon gene by B cell lines that express CD30. These results demonstrate the
      various members of the TNF family exert specific effects on human B cell
      function, with CD40L and CD30L providing powerful, but opposing, effects on l
      epsilon transcription.

PMID- 7650372
TI  - Functional expression and recognition of nonclassical MHC class I T10b is not
      peptide-dependent.
AB  - Studies of classical and nonclassical MHC class I molecules have shown that
      unique peptides are associated and functionally recognized by alloreactive T
      cells. We have recently shown that an alloreactive TCR-gamma delta cell
      recognizes a nonclassical MHC molecule, T10b. However, T cell recognition of this
      glycoprotein did not appear to require typical peptide recognition based on
      studies using transporter-defective mutant cell lines. In the current study, we
      have analyzed in detail, the role of peptide in T10b expression and recognition.
      The findings reveal that the recognition of the nonclassical MHC molecule by TCR
      gamma delta cells is independent of species, tissue type, both the class I and
      class II Ag processing and presentation pathways, or the presence of peptides. In
      fact, biochemical analysis of the T10b chimeric molecule, T10b/Ld, transfected
      into CHO cells using radiolabeled [3H]leucine, HPLC, and mass spectrometry
      suggest that peptides are not associated with this nonclassical class I molecule.
      Therefore, some class I molecules, e.g., T10b, do not associate with polymorphic
      peptides typical of classical MHC class I molecules and can be expressed in the
      absence of peptides on the cell surface in a functionally active form.

PMID- 7650373
TI  - Kinetics of Th1 and Th2 cytokine production during the early course of acute and
      chronic murine graft-versus-host disease. Regulatory role of donor CD8+ T cells.
AB  - Acute and chronic graft-versus-host disease (GVHD) in the parent-into-F1 model
      are mediated by predominantly cellular or humoral immune responses, respectively,
      and are strikingly different entities by 2 wk of disease. Both forms of GVHD,
      however, evolve from a common starting point, i.e., donor CD4+ T cell recognition
      of host alloantigen and IL-2 production. Our study examines the first 2 wk of
      GVHD to delineate the events that critically influence GVHD development.
      Surprisingly, both forms of GVHD are initially characterized by increased Th2
      cytokine (IL-4 and IL-10) production and B cell activation which persists into wk
      2. The earliest distinguishing features of acute GVHD were detectable at days 5
      through 7 of disease and consisted of 1) expansion of donor CD8+ T cells, and 2)
      increased IFN-gamma production by donor CD4+ and CD8+ T cells. Interestingly, IFN
      gamma production by donor CD4+ T cells was not seen if donor CD8+ T cells were
      not engrafted in comparable numbers. Chronic GVHD in the DBA-into-BDF1 model was
      found to be caused by a relative defect in the ability of DBA CD8+ T cells to
      induce acute GVHD and to produce IFN-gamma. These studies demonstrate that both
      acute and chronic GVHD begin as a Th2 cytokine-mediated, B cell stimulatory
      response. The transition to acute GVHD is critically dependent on the engraftment
      of donor CD8+ T cells, which terminate B cell hyperactivity by 1) eliminating
      activated B cells and 2) promoting IFN-gamma secretion by donor CD4+ T cells.

PMID- 7650375
TI  - Allelic differences in the VHOx-1 gene explain the absence of a B cell clonal
      dominance in the primary response of C57BL/6 mice to phthalate.
AB  - A highly conserved Id (CRIXmp-1) associated with the murine (BALB/c) humoral
      immune response to the hapten phthalate (Xmp) is conspicuously absent in C57BL/6
      mice. The absence of this Id in C57BL/6 mice is shown here to be due to the
      absence of the appropriate VH gene (VHOx-1) usage in the Xmp response. To
      determine whether the failure to utilize this VH was due to an active suppression
      or to the lack of the requisite VH gene in the available repertoire, VHOx-1 gene
      specific primers were used to amplify the germ-line VHOx-1 gene from genomic DNA
      from BALB/c and C57BL/6 mice. The germ-line coding sequence of the C57BL/6 allele
      of the VHOx-1 gene is 99% similar to the germ-line coding sequence of the BALB/c
      allele. Amplification of cDNA made from splenic RNA from C57BL/6 mice confirmed
      that this gene is expressed. There are four nucleotide differences that lead to
      three amino acid changes in the predicted protein sequence. Each change is either
      in or immediately adjacent to a complementarity-determining region (CDR). Two of
      these changes are unique to the C57BL/6 allele and are not shared with CRIXmp-1
      expressing strains. These two changes are predicted to alter the Xmp binding
      capabilities of the C57BL/6 allelic form of this VH gene, thereby explaining the
      absence of the Xmp-1 clonotype, which is dominant in the primary Xmp immune
      response of most other strains of mice.

PMID- 7650376
TI  - Extensive TCR junctional diversity of V gamma 9/V delta 2 clones from human
      female reproductive tissues.
AB  - Panels of gamma delta T cell clones bearing the V gamma 9/V delta 2 form of TCR
      were derived from human first trimester decidualized endometrium and cervix.
      Seventy-three percent of these clones expressed the human mucosal lymphocyte Ag
      HML-1 compared with only 14% of PBL V gamma 9/V delta 2 clones, indicating that
      most clones were derived from the tissue itself rather than contaminating
      peripheral blood. All 13 clones isolated expressed V gamma 9JPC gamma 1- and V
      delta 2(D)J delta 1-encoded receptors; TCR gamma and delta junctional regions
      from most of these were sequenced and analyzed, together with the TCR-delta
      junctional region of a sequence obtained from bulk CD3+ decidual leukocytes.
      There was considerable junctional diversity of both gamma- and delta-chains with
      a similar extent of germline V and J gene trimming and N-region nucleotide
      addition to that found in PBL V gamma 9/V delta 2 cells. Eight of eleven TCR
      delta junctional sequences contained a strongly hydrophobic amino acid in
      position 97, as has been found in > 90% o V gamma 9/V delta 2 clones. Thymic V
      gamma 9/V delta 2 cells show much less junctional diversity and less pronounced
      selection at residue 97 of the delta-chain. Thus, unlike the mouse, gamma delta T
      cells from human female reproductive tissues exhibit extensive TCR junctional as
      well as combinatorial diversity. This suggests that V gamma 9/V delta 2 cells in
      these human tissues have undergone selective but diverse peripheral expansion in
      response to antigenic stimuli in a similar manner to those in peripheral blood.

PMID- 7650374
TI  - Deoxyspergualin inhibits kappa light chain expression in 70Z/3 pre-B cells by
      blocking lipopolysaccharide-induced NF-kappa B activation.
AB  - Deoxyspergualin (DSG) is a potent immunosuppressive agent that is currently
      undergoing clinical trials for treatment of transplant rejection, preventive of
      human anti-mouse Ab response, and blocking autoimmune disease progression. The
      mechanism of action of DSG appears to be novel, with in vivo activity
      attributable to the suppression of both humoral and cell-mediated immunity. In
      this study we investigated the effect of DSG on the induction of lg expression in
      the 70Z/3 murine pre-B cell line. Treatment of 70Z/3 cells with DSG for 24, 48,
      or 72 h before LPS or IFN-gamma induction resulted in a time-dependent inhibition
      of surface lgM expression, with greater than 80% inhibition observed after 72 h
      of pretreatment. Inhibition of surface expression was specific for lgM, as
      neither MHC class I nor CD45 (B220) surface expression was affected by DSG
      pretreatment. Cyclosporin A was ineffective at suppressing surface igM induction.
      DSG pretreatment results in a 10-fold reduction in LPS- or IFN-gamma-induced
      kappa L chain protein and mRNA expression. No change was observed in either mu or
      beta-actin mRNA levels. Analysis of nuclear and cytoplasmic NF-kappa B expression
      using electrophoretic mobility shift analysis and Western analysis, revealed that
      DSG blocked LPS-induced NF-kappa B nuclear translocation, but had no effect on
      cytoplasmic NF-kappa B levels. We conclude that DSG may act to suppress humoral
      immune responses by blocking the transcriptional activation of kappa L chain
      expression during certain stages of B cell development.

PMID- 7650377
TI  - HLA-DQ polymorphisms are highly selective for peptide binding interactions.
AB  - The impact of HLA-DQ allelic polymorphism on peptide binding interactions was
      investigated. MHC class II binding peptides from lambda repressor (lambda R),
      thyroid peroxidase (TPO), and a modified poly-alanine peptide (AKY) were used in
      two different binding assays, one with purified DQ molecules and another with
      cells that expressed DQ cell surface dimers. Class II heterodimers of different
      combinations of DQ alpha-chain and the DQ beta-chain independently influenced
      specific peptide interactions. Each of the peptides tested bound differentially
      to DQ alleles: TPO632-645 bound test to DQ2 molecules (DQA1*0501/DQB1*0201),
      lambda R12-24 bound best to DQ8 molecules (DQ3.2 or DQA1*0301/DQB1*0302), and AYK
      bound best to DQ1 (DQA*0102/DQB*0602) and DQ7 (DQ3.1 OR DQA1*0301/DQB1*0301).
      However, in each case in which either the DQ alpha- or DQ beta-chain was
      exchanged, major alterations or reversals of this pattern of interaction were
      observed. The interaction of lambda R with DQ8 was highly dependent on specific
      sequence polymorphisms at residue 57; an Ala-->Asp substitution on the DQ beta
      chain at the polymorphic codon 57 prevented peptide binding. However, Ala 57
      alone was not sufficient to permit binding in other DQ allelic contexts. These
      studies demonstrate the critical role of specific DQ polymorphisms in
      establishing the nature of bound Ag and thereby influencing the potential immune
      repertoire. Analysis of the ability of DQ molecules to bind and present antigenic
      peptides should aid in understanding their role in immunity and in development of
      HLA-DQ-associated autoimmune disease.

PMID- 7650380
TI  - Identification and localization of a developmental stage-specific promoter
      activity from the murine lambda 5 gene.
AB  - The lambda 5 protein is expressed in pre-B cells in association with VpreB and mu
      heavy chains, and is critical for differentiation to the B cell stage. Pre-B cell
      specific expression of the lambda 5 and VpreB genes is regulated at the level of
      transcription initiation. In this report, we have identified several DNase l
      hypersensitive sites 2.5- to 6.0-kb downstream of the lambda 5 gene, which are
      present in the pre-B cell line 70Z/3, but not in the myeloma cell line j558L.
      These sites, however, were shown to have no transcriptional enhancer activity as
      measured by transient transfection. Enhancer activity was identified within a 361
      bp fragment (-296 to +65, where +1 is the major 5' transcription initiation site)
      upstream of the mouse lambda 5 gene. This activity is orientation and position
      independent, and is also tissue and differentiation stage specific (active in pre
      B but not B and T cells). Deletion constructs indicate that three adjacent areas
      (-210 to -169, -153 to -64, and -64 to -22) are all necessary for enhancer
      activity. Pre-B cell-specific promoter activity was shown to reside within the 
      219 to +109 fragment. Basal promoter activity resides within the -64 to +109
      fragment, but is not tissue specific or stage specific. A negative element within
      the -101 to -64 region is active in all lymphoid cell lines tested and therefore
      cannot by itself be responsible for the tissue and stage specificity. The data
      indicate that the elements responsible for the enhancer activity (-210 to -22)
      are part of the lambda 5 gene promoter and likely confer the tissue and stage
      specificity via positive elements within the -210 to -22 region.

PMID- 7650379
TI  - Myeloma Ig heavy chain V region sequences reveal prior antigenic selection and
      marked somatic mutation but no intraclonal diversity.
AB  - The lg VH region sequence in 48 patients with multiple myeloma (MM) was analyzed
      to characterize the malignant cell of origin. The sequences were obtained after
      amplification of bone marrow cDNA by using VH family-specific and CH primers,
      then compared with either directly sequenced patient germ-line or published VH
      gen sequences to assay for somatic mutation. Because somatic hypermutation of the
      VH gene occurs late in B cell development, its presence has been helpful in
      determining the cell of origin in other B cell malignancies. Overall, a median of
      8.2% of the nucleotides had evidence of substitution within each VH gene sequence
      (range=2.7% to 16.5%), which is more prevalent than in any other reported tumor
      type. Strong evidence of prior antigenic selection pressure was also evident. The
      ratio of nucleotide substitutions that resulted in amino acid replacement was
      significantly higher in the complementarity-determining region than in the
      framework region (3.25 vs 1.56, respectively; p < 0.00005). No VH gene
      intraclonal diversity was noted, despite sequencing multiple clones (3-16) from
      each patient, nor was there evidence of further VH gene somatic mutation over the
      course of three patients' disease. These findings strongly imply that the
      malignant clone in MM evolves from a cell late in B cell development.

PMID- 7650378
TI  - Organization, regulatory sequences, and alternatively spliced transcripts of the
      mucosal addressin cell adhesion molecule-1 (MAdCAM-1) gene.
AB  - The mucosal addressin cell adhesion molecule-1 (MAdCAM-1) is expressed
      selectively at venular sites of lymphocyte extravasation into mucosal lymphoid
      tissues and lamina propria, where it directs local lymphocyte trafficking. MAdCAM
      1 is a multifunctional type l transmembrane adhesion molecule comprising two
      distal lg domains involved in alpha 4 beta 7 integrin binding, a mucin-like
      region able to display L-selectin-binding carbohydrates, and a membrane-proximal
      lg domain homologous to lgA. We show in this work that the MAdCAM-1 gene is
      located on chromosome 10 and contains five exons. The signal peptide and each one
      of the three lg domains are encoded by a distinct exon, whereas the
      transmembrane, cytoplasmic tail, and 3'-untranslated region of MAdCAM-1 are
      combined on a single exon. The mucin-like region and the third lg domain are
      encoded together on exon 4. An alternatively spliced MAdCAM-1 mRNA is identified
      that lacks the mucin/lgA-homologous exon 4-encoded sequences. This short variant
      of MAdCAM-1 may be specialized to support alpha 4 beta 7-dependent adhesion
      strengthening, independent of carbohydrate-presenting function. Sequences 5' of
      the transcription start site include tandem nuclear factor-kappa B sites; AP-1,
      AP-2, and signal peptide-1 binding sites; and an estrogen response element. Our
      findings reinforce the correspondence between the multidomain structure and
      versatile functions of this vascular addressin, and suggest an additional level
      of regulation of carbohydrate-presenting capability, and thus of its importance
      in lectin-mediated vs alpha 4 beta 7-dependent adhesive events in lymphocyte
      trafficking.